Search results for: Vero cell line

Authors: Geetanjali Panda, Suvrakanti Chakraborty

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In this paper, Newton-like descent methods are proposed for unconstrained optimization problems, which use q-derivatives of the gradient of an objective function. First, a local scheme is developed with alternative sufficient optimality condition, and then the method is extended to a global scheme. Moreover, a variant of practical Newton scheme is also developed introducing a real sequence. Global convergence of these schemes is proved under some mild conditions. Numerical experiments and graphical illustrations are provided. Finally, the performance profiles on a test set show that the proposed schemes are competitive to the existing first-order schemes for optimization problems.

Keywords: Descent algorithm, line search method, q calculus, Quasi Newton method

Procedia PDF Downloads 398

Authors: Jeff Moussodji, Dominique Drouin

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The highly complex technology requirements of today’s integrated circuits (ICs), lead to the increased use of several materials types such as metal structures, brittle and porous low-k materials which are used in both front end of line (FEOL) and back end of line (BEOL) process for wafer manufacturing. In order to singulate chip from wafer, a critical laser-grooving process, prior to blade dicing, is used to remove these layers of materials out of the dicing street. The combination of laser-grooving and blade dicing allows to reduce the potential risk of induced mechanical defects such micro-cracks, chipping, on the wafer top surface where circuitry is located. It seems, therefore, essential to have a fundamental understanding of the physics involving laser-dicing in order to maximize control of these critical process and reduce their undesirable effects on process efficiency, quality, and reliability. In this paper, the study was based on the convergence of two approaches, numerical and experimental studies which allowed us to investigate the interaction of a nanosecond pulsed laser and BEOL wafer materials. To evaluate this interaction, several laser grooved samples were compared with finite element modeling, in which three different aspects; phase change, thermo-mechanical and optic sensitive parameters were considered. The mathematical model makes it possible to highlight a groove profile (depth, width, etc.) of a single pulse or multi-pulses on BEOL wafer material. Moreover, the heat affected zone, and thermo-mechanical stress can be also predicted as a function of laser operating parameters (power, frequency, spot size, defocus, speed, etc.). After modeling validation and calibration, a satisfying correlation between experiment and modeling, results have been observed in terms of groove depth, width and heat affected zone. The study proposed in this work is a first step toward implementing a quick assessment tool for design and debug of multiple laser grooving conditions with limited experiments on hardware in industrial application. More correlations and validation tests are in progress and will be included in the full paper.

Keywords: laser-dicing, nano-second pulsed laser, wafer multi-stack, multiphysics modeling

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Authors: T. Mcgraw, F. N. Morin, N. Desai

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Background: Antimicrobial resistance is a critical issue in global health care and a significant contributor to increased patient morbidity and mortality. Suspected urinary tract infection (UTI) is a key area of inappropriate antibiotic prescription in pediatrics. Management patterns of infectious diseases have been shown to vary by provider type within a single setting. The aim of this study was to assess compliance with national UTI management guidelines by nurse practitioners in a pediatric emergency department (ED). Methods: This was a post-hoc analysis of a retrospective cohort study to review and evaluate visits to a tertiary care freestanding pediatric emergency department. Patients were included if they were 60 days to 36 months old and discharged with a diagnosis of UTI or ‘rule-out UTI’ between July 2015 and July 2020. Primary outcome measure was proportion of visits seen by Nurse Practitioners (NP) which were associated with national guideline compliance in the diagnosis and treatment of suspected UTI. We performed descriptive statistics and comparative analyses to determine differences in practice patterns between NPs, and physicians. Results: A total of 636 charts were reviewed, of which 402 patients met inclusion criteria. 17 patients were treated by NPs, 385 were treated by either Pediatric Emergency Medicine physicians (PEM) or non-PEM physicians. Overall, the proportion of infants receiving guideline-compliant care was 25.9% (21.8-30.4%). Of those who were prescribed antibiotics, 79.6% (74.7-83.8%) received first line guideline recommended therapy and 58.9% (53.8-63.8%) received fully compliant therapy with respect to age, dose, duration, and frequency. In patients treated by NPs, 16/17 (94%(95% CI:73.0-99.0)) required antibiotics, 15/16 (93%(95% CI: 71.7-98.9)) were treated with first line agent (cephalexin), 8/16 (50%(95% CI:28-72)) were guideline compliant of dose and duration. 5/8 (63%(95% CI:30.6-86.3)) were noncompliant for dose being too high. There was no difference in receiving guideline compliant empiric antibiotic therapy between physicians and nurse practitioners (OR: 0.837 CI: 0.302-2.69). Conclusion: In this post-hoc analysis, guideline noncompliance by nurse practitioners is common in children tested and treated for UTIs in a pediatric emergency department. Care by a Nurse Practitioner was not associated with greater rate of noncompliance than care by a Pediatric Emergency Medicine physician. Future appropriately powered studies may focus on confirming these results.

Keywords: antibiotic stewardship, infectious disease, nurse practitioner, urinary tract infection

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Authors: Abdullahi Bn Umar

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Over the years curriculum planners and researchers in education have continued to seek for ways to improve teaching and learning by way of varying approaches to curriculum and instruction in line with dynamic nature of knowledge. In this regards various innovative strategies to teaching and learning have been adopted to match with the technological advancement in education particularly in the aspect of instructional delivery through Information Communication Technology (ICT) as a tools. This paper reviews some innovative strategies and how they impact on learner’s achievement and educational development in Nigeria. The paper concludes by recommending innovative approach appropriate for use in Nigerian context.

Keywords: innovation, instructional delivery, virtual laboratory, educational design

Procedia PDF Downloads 483

Authors: Mesih Kocamuftuoglu, Gonca Ozan, Enver Ozan, Nalan Kaya, Sema Temizer Ozan

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Metabolic Syndrome, one of the common metabolic disorder, occurs with co-development of insulin resistance, obesity, dislipidemia and hypertension problems. Insulin resistance appears to play a pathogenic role in the metabolic syndrome. Also, there is a relationship between insulin resistance and infertility as known. Turmeric (Curcuma longa L.) a polyphenolic chemical is widely used for its coloring, flavoring, and medicinal properties, and exhibits a strong antioxidant activity. In this study, we assess the effects of turmeric on rat uterine tissue in metabolic syndrome model induced by high fructose diet. Thirty-two adult female Wistar rats weighing 220±20 g were randomly divided into four groups (n=8) as follows; control, fructose, turmeric, and fructose plus turmeric. Metabolic syndrome was induced by fructose solution 20% (w/v) in tap water, and turmeric (C.Longa) administered at the dose of 80 mg/kg body weight every other day by oral gavage. After the experimental period of 8 weeks, rats were decapitated, serum and uterine tissues were removed. Serum lipid profile, glucose, insülin levels were measured. Uterine tissues were fixed for histological analyzes. The uterine tissue sections were stained with hematoxylin-eosin (H & E) stain, then examined and photographed on a light microscope (Novel N-800Mx20). As a result, fructose consumption effected serum lipids, insulin levels, and insulin resistance significantly. Endometrium and myometrium layers were observed in normal structure in control group of uterine tissues. Perivascular edema, peri glandular fibrosis, and inflammatory cell increase were detected in fructose group. Sections of the fructose plus turmeric group showed a significant improvement in findings when compared to the fructose group. Turmeric group cell structures were observed similar with the control group. These results demonstrated that high-fructose consumption could change the structure of the uterine tissue. On the other hand, turmeric administration has beneficial effects on uterine tissue at that dose and duration when administered with fructose.

Keywords: metabolic syndrome, rat, turmeric, uterus

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Authors: Feddaoui Amina

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Through this study we will try to shed light on the theoretical framework proposed for understanding creative accounting as a financial numbers game and one of the most important techniques of accounts manipulation, its main actors and its practices. We will discover the role of the modified Jones model (1995) in detecting creative accounting practices using discretionary accruals. Finally we will try to confirm the importance and the need to address this type of practices using corporate governance as a main control system and an important defense line to reduce these dangerous accounts manipulation.

Keywords: financial numbers game, creative accounting, modified Jones model, accounts manipulation

Procedia PDF Downloads 477

Authors: Shengjun Zhang, Xu Cheng, Feng Shen

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The passive containment cooling system (PCCS) is widely used in the advanced nuclear reactor in case of the loss of coolant accident (LOCA) and the main steam line break accident (MSLB). The internal heat exchanger is one of the most important equipment in the PCCS and its heat transfer characteristic determines the performance of the system. In this investigation, a theoretical model is presented for predicting the heat and mass transfer which accompanies condensation. The conduction through the liquid condensate is considered and the interface temperature is defined by iteration. The parameter in the correlation to describe the suction effect should be further determined through experimental data.

Keywords: non-condensable gas, condensation, heat transfer coefficient, heat and mass transfer analogy

Procedia PDF Downloads 350

Authors: E. Kilicay, Z. Karahaliloglu, B. Hazer, E. B. Denkbas

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In this study, we have prepared concanavaline A (ConA) functionalized curcumin (CUR) loaded PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles as a novel and efficient drug delivery system. CUR is a promising anticancer agent for various cancer types. The aim of this study was to evaluate therapeutic potential of curcumin loaded PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin loaded NPs (ConA-CUR NPs) for ovarian cancer treatment. ConA was covalently connected to the carboxylic group of nanoparticles by EDC/NHS activation method. In the ligand attachment experiment, the binding capacity of ConA on the surface of NPs was found about 90%. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were smooth and spherical in shape. The size and zeta potential of prepared NPs were about 228±5 nm and −21.3 mV respectively. ConA-CUR NPs were characterized by FT-IR spectroscopy which confirmed the existence of CUR and ConA in the nanoparticles. The entrapment and loading efficiencies of different polymer/drug weight ratios, 1/0.125 PHBHHx/CUR= 1.25CUR-NPs; 1/0.25 PHBHHx/CUR= 2.5CUR-NPs; 1/0.5 PHBHHx/CUR= 5CUR-NPs, ConA-1.25CUR NPs, ConA-2.5CUR NPs and ConA-5CUR NPs were found to be ≈ 68%-16.8%; 55%-17.7 %; 45%-33.6%; 70%-15.7%; 60%-17%; 51%-30.2% respectively. In vitro drug release showed that the sustained release of curcumin was observed from CUR-NPs and ConA-CUR NPs over a period of 19 days. After binding of ConA, the release rate was slightly increased due to the migration of curcumin to the surface of the nanoparticles and the matrix integrities was decreased because of the conjugation reaction. This functionalized nanoparticles demonstrated high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. Anticancer activity of ConA-CUR NPs was proved by MTT assay and reconfirmed by apoptosis and necrosis assay. The anticancer activity of ConA-CUR NPs was measured in ovarian cancer cells (SKOV-3) and the results revealed that the ConA-CUR NPs had better tumor cells decline activity than free curcumin. The nacked nanoparticles have no cytotoxicity against human ovarian carcinoma cells. Thus the developed functionalized nanoformulation could be a promising candidate in cancer therapy.

Keywords: curcumin, curcumin-PHBHHx nanoparticles, concanavalin A, concanavalin A-curcumin PHBHHx nanoparticles, PHBHHx nanoparticles, ovarian cancer cell

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Authors: Lev Chernyshev, Ekaterina Lieshout, Natalia Kabaliuk

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Sit-skis enable individuals with limited lower limb or core movement to ski unassisted confidently. The rise in popularity of the Winter Paralympics has seen an influx of engineering innovation, especially for the Downhill and Super-Giant Slalom events, where the athletes achieve speeds as high as 160km/h. The growth in the sport has inspired recent research into sit-ski aerodynamics. Crosswinds are expected in mountain climates and, therefore, can greatly impact a skier's maneuverability and aerodynamics. This research investigates the impact of crosswinds on the drag force of a Paralympic sit-ski using Computational Fluid Dynamics (CFD). A Paralympic sit-ski with a model of a skier, a leg cover, a bucket seat, and a simplified suspension system was used for CFD analysis in ANSYS Fluent. The hybrid initialisation tool and the SST k–ω turbulence model were used with two tetrahedral mesh bodies of influence. The crosswinds (10, 30, and 50 km/h) acting perpendicular to the sit-ski's direction of travel were simulated, corresponding to the straight-line skiing speeds of 60, 80, and 100km/h. Following the initialisation, 150 iterations for both first and second order steady-state solvers were used, before switching to a transient solver with a computational time of 1.5s and a time step of 0.02s, to allow the solution to converge. CFD results were validated against wind tunnel data. The results suggested that for all crosswind and sit-ski speeds, on average, 64% of the total drag on the ski was due to the athlete's torso. The suspension was associated with the second largest overall sit-ski drag force contribution, averaging at 27%, followed by the leg cover at 10%. While the seat contributed a negligible 0.5% of the total drag force, averaging at 1.2N across the conditions studied. The effect of the crosswind increased the total drag force across all skiing speed studies, with the drag on the athlete's torso and suspension being the most sensitive to the changes in the crosswind magnitude. The effect of the crosswind on the ski drag reduced as the simulated skiing speed increased: for skiing at 60km/h, the drag force on the torso increased by 154% with the increase of the crosswind from 10km/h to 50km/h; whereas, at 100km/h the corresponding drag force increase was halved (75%). The analysis of the flow and pressure field characteristics for a sit-ski in crosswind conditions indicated the flow separation localisation and wake size correlated with the magnitude and directionality of the crosswind relative to straight-line skiing. The findings can inform aerodynamic improvements in sit-ski design and increase skiers' medalling chances.

Keywords: sit-ski, aerodynamics, CFD, crosswind effects

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Authors: S. Abdourraziq, M. A. Abdourraziq

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One of the most famous and important applications of solar energy systems is water pumping. It is often used for irrigation or to supply water in countryside or private firm. However, the cost and the efficiency are still a concern, especially with a continued variation of solar radiation and temperature throughout the day. Then, the improvement of the efficiency of the system components is one of the different solutions to reducing the cost. In this paper, we will present a detailed definition of each element of a PV pumping system, and we will present the different MPPT algorithm used in the literature. Our system consists of a PV panel, a boost converter, a motor-pump set, and a storage tank.

Keywords: PV cell, converter, MPPT, MPP, PV pumping system

Procedia PDF Downloads 158

Authors: Alireza Shams, Ali Zamanian, Atefehe Shamosi, Farnaz Ghorbani

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Introduction: Although the application of a new strategy remains a remarkable challenge for treatment of disabilities due to neuronal defects, progress in Nanomedicine and tissue engineering, suggesting the new medical methods. One of the promising strategies for reconstruction and regeneration of nervous tissue is replacing of lost or damaged cells by specific scaffolds after Compressive, ischemic and traumatic injuries of central nervous system. Furthermore, ultrastructure, composition, and arrangement of tissue scaffolds are effective on cell grafts. We followed implantation and differentiation of mesenchyme stem cells to neural cells on Gelatin Polylactic-co-glycolic acid (PLGA) scaffolds coated with iron nanoparticles. The aim of this study was to evaluate the capability of stem cells to differentiate into motor neuron-like cells under topographical cues and morphogenic factors. Methods and Materials: Bone marrow mesenchymal stem cells (BMMSCs) was obtained by primary cell culturing of adult rat bone marrow got from femur bone by flushing method. BMMSCs were incubated with DMEM/F12 (Gibco), 15% FBS and 100 U/ml pen/strep as media. Then, BMMSCs seeded on Gel/PLGA scaffolds and tissue culture (TCP) polystyrene embedded and incorporated by Fe Nano particles (FeNPs) (Fe3o4 oxide (M w= 270.30 gr/mol.). For neuronal differentiation, 2×10 5 BMMSCs were seeded on Gel/PLGA/FeNPs scaffolds was cultured for 7 days and 0.5 µ mol. Retinoic acid, 100 µ mol. Ascorbic acid,10 ng/ml. Basic fibroblast growth factor (Sigma, USA), 250 μM Iso butyl methyl xanthine, 100 μM 2-mercaptoethanol, and 0.2 % B27 (Invitrogen, USA) added to media. Proliferation of BMMSCs was assessed by using MTT assay for cell survival. The morphology of BMMSCs and scaffolds was investigated by scanning electron microscopy analysis. Expression of neuron-specific markers was studied by immunohistochemistry method. Data were analyzed by analysis of variance, and statistical significance was determined by Turkey’s test. Results: Our results revealed that differentiation and survival of BMMSCs into motor neuron-like cells on Gel/PLGA/FeNPs as a biocompatible and biodegradable scaffolds were better than those cultured in Gel/PLGA in absence of FeNPs and TCP scaffolds. FeNPs had raised physical power but decreased capacity absorption of scaffolds. Well defined oriented pores in scaffolds due to FeNPs may activate differentiation and synchronized cells as a mechanoreceptor. Induction effects of magnetic FeNPs by One way flow of channels in scaffolds help to lead the cells and can facilitate direction of their growth processes. Discussion: Progression of biological properties of BMMSCs and the effects of FeNPs spreading under magnetic field was evaluated in this investigation. In vitro study showed that the Gel/PLGA/FeNPs scaffold provided a suitable structure for motor neuron-like cells differentiation. This could be a promising candidate for enhancing repair and regeneration in neural defects. Dynamic and static magnetic field for inducing and construction of cells can provide better results for further experimental studies.

Keywords: differentiation, mesenchymal stem cells, nano particles, neuronal defects, Scaffolds

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Authors: Emin Gundogar, Burak Erkayman, Nusret Sazak

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Providing effective management performance through the whole supply chain is critical issue and hard to applicate. The proper evaluation of integrated data may conclude with accurate information. Analysing the supply chain data through OLAP (On-Line Analytical Processing) technologies may provide multi-angle view of the work and consolidation. In this study, association rules and classification techniques are applied to measure the supply chain performance metrics of an automotive manufacturer in Turkey. Main criteria and important rules are determined. The comparison of the results of the algorithms is presented.

Keywords: supply chain performance, performance measurement, data mining, automotive

Procedia PDF Downloads 513

Authors: Zhongzhi Hu, Jie Shen, Jiqiang Wang

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A high precision aeroengine model is needed when developing the engine control system. Compared with other main components, the axial compressor is the most challenging component to simulate. In this paper, a compressor map optimizing tool based on the introduction of a modifiable β function is developed for FWorks (FADEC Works). Three parameters (d density, f fitting coefficient, k₀ slope of the line β=0) are introduced to the β function to make it modifiable. The comparison of the traditional β function and the modifiable β function is carried out for a certain type of compressor. The interpolation errors show that both methods meet the modeling requirements, while the modifiable β function can predict compressor performance more accurately for some areas of the compressor map where the users are interested in.

Keywords: beta function, compressor map, interpolation error, map optimization tool

Procedia PDF Downloads 267

Authors: Sandra Pietri, Helene Dubout, Sabrina Ena, Candice Hoste, Enrico Bastianelli

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Bone Therapeutics is a bone cell therapy company addressing high unmet medical needs in the field of bone fracture repair, more specifically in non-union and delayed-union fractures where the bone repair process is impaired. The company has developed a unique allogeneic osteoblastic cell product (ALLOB®) derived from bone marrow which is currently tested in humans in the indication of delayed-union fractures. The purpose of our study was to directly compare ALLOB® vs. non-differentiated mesenchymal stem cells (MSC) for their in vitro osteogenic characteristics and their in vivo osteogenic potential in order to determine which cellular type would be the most adapted for bone fracture repair. Methods: Healthy volunteers’ bone marrow aspirates (n=6) were expended (i) into BM-MSCs using a complete MSC culture medium or (ii) into ALLOB® cells according to its manufacturing process. Cells were characterized in vitro by morphology, immunophenotype, gene expression and differentiation potential. Additionally, their osteogenic potential was assessed in vivo in the subperiosteal calvaria bone formation model in nude mice. Results: The in vitro side-by-side comparison studies showed that although ALLOB® and BM-MSC shared some common general characteristics such as the 3 minimal MSC criteria, ALLOB® expressed significantly higher levels of chondro/osteoblastic genes such as BMP2 (fold change (FC) > 100), ALPL (FC > 12), CBFA1 (FC > 3) and differentiated significantly earlier than BM-MSC toward the osteogenic lineage. Moreover the bone formation model in nude mice demonstrated that used at the same cellular concentration, ALLOB® was able to induce significantly more (160% vs.107% for control animals) bone formation than BM-MSC (118% vs. 107 % for control animals) two weeks after administration. Conclusion: Our side-by-side comparison studies demonstrated that in vitro and in vivo, ALLOB® displays superior osteogenic capacity to BM-MScs and is therefore a better candidate for the treatment of bone fractures.

Keywords: gene expression, histomorphometry, mesenchymal stem cells, osteogenic differentiation potential, preclinical

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Authors: Ruth Goldschmidt, Vyacheslav Kalchenko, Lilah Agemy, Rachel Elmoalem, Avigdor Scherz

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Vascular Targeted Photodynamic therapy (VTP) is a new modality for selective cancer treatment that leads to the complete tumor ablation. A photosensitizer, a bacteriochlorophyll derivative in our case, is first administered to the patient and followed by the illumination of the tumor area, by a near-IR laser for its photoactivation. The photoactivated drug releases reactive oxygen species (ROS) in the circulation, which reacts with blood cells and the endothelium leading to the occlusion of the blood vasculature. If the blood vessels are only partially closed, the tumor may recover, and cancer cells could survive. On the other hand, excessive treatment may lead to toxicity of healthy tissues nearby. Simultaneous VTP monitoring and image processing independent of the photoexcitation laser has not yet been reported, to our knowledge. Here we present a method for blood flow monitoring, using a real-time laser speckle imaging (RTLSI) in the tumor during VTP. We have synthesized over the years a library of bacteriochlorophyll derivatives, among them WST11 and STL-6014. Both are water soluble derivatives that are retained in the blood vasculature through their partial binding to HSA. WST11 has been approved in Mexico for VTP treatment of prostate cancer at a certain drug dose, and time/intensity of illumination. Application to other bacteriochlorophyll derivatives or other cancers may require different treatment parameters (such as light/drug administration). VTP parameters for STL-6014 are still under study. This new derivative mainly differs from WST11 by its lack of the central Palladium, and its conjugation to an Arg-Gly-Asp (RGD) sequence. RGD is a tumor-specific ligand that is used for targeting the necrotic tumor domains through its affinity to αVβ3 integrin receptors. This enables the study of cell-targeted VTP. We developed a special RTLSI module, based on Labview software environment for data processing. The new module enables to acquire raw laser speckle images and calculate the values of the laser temporal statistics of time-integrated speckles in real time, without additional off-line processing. Using RTLSI, we could monitor the tumor’s blood flow following VTP in a CT26 colon carcinoma ear model. VTP with WST11 induced an immediate slow down of the blood flow within the tumor and a complete final flow arrest, after some sporadic reperfusions. If the irradiation continued further, the blood flow stopped also in the blood vessels of the surrounding healthy tissue. This emphasizes the significance of light dose control. Using our RTLSI system, we could prevent any additional healthy tissue damage by controlling the illumination time and restrict blood flow arrest within the tumor only. In addition, we found that VTP with STL-6014 was the most effective when the photoactivation was conducted 4h post-injection, in terms of tumor ablation success in-vivo and blood vessel flow arrest. In conclusion, RTSLI application should allow to optimize VTP efficacy vs. toxicity in both the preclinical and clinical arenas.

Keywords: blood vessel occlusion, cancer treatment, photodynamic therapy, real time imaging

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Authors: Ananya Gupta, Sangeeta Bhaskar

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Mycobacterium indicus pranii (MIP) is a saprophytic mycobacterium. It is a predecessor of M. avium complex (MAC). Whole genome analysis and growth kinetics studies have placed MIP in between pathogenic and non-pathogenic species. It shares significant antigenic repertoire with M. tuberculosis and have unique immunomodulatory properties. MIP provides better protection than BCG against pulmonary tuberculosis in animal models. Immunization with MIP by aerosol route provides significantly higher protection as compared to immunization by subcutaneous (s.c.) route. However, mechanism behind differential protection has not been studied. In this study, using mice model we have evaluated and compared the M.tb specific immune response in lung compartments (airway lumen / lung interstitium) as well as spleen following MIP immunization via nasal (i.n.) and s.c. route. MIP i.n. vaccination resulted in increased seeding of memory T cells (CD4+ and CD8+ T-cells) in the airway lumen. Frequency of CD4+ T cells expressing Th1 migratory marker (CXCR3) and activation marker (CD69) were also high in airway lumen of MIP i.n. group. Significantly high ex vivo secretion of cytokines- IFN-, IL-12, IL-17 and TNF- from cells of airway luminal spaces provides evidence of antigen-specific lung immune response, besides generating systemic immunity comparable to MIP s.c. group. Analysis of T cell response on per cell basis revealed that antigen specific T-cells of MIP i.n. group were functionally superior as higher percentage of these cells simultaneously secreted IFN-gamma, IL-2 and TNF-alpha cytokines as compared to MIP s.c. group. T-cells secreting more than one of the cytokines simultaneously are believed to have robust effector response and crucial for protection, compared with single cytokine secreting T-cells. Adoptive transfer of airway luminal T-cells from MIP i.n. group into trachea of naive B6 mice revealed that MIP induced CD8 T-cells play crucial role in providing long term protection. Thus the study demonstrates that MIP intranasal vaccination induces M.tb specific memory T-cells in the airway lumen that results in an early and robust recall response against M.tb infection.

Keywords: airway lumen, Mycobacterium indicus pranii, Th1 migratory markers, vaccination

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Authors: Changhan Ouyang, Zhonglin Xie

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In response to proatherosclerotic factors such as oxidized lipids, or to therapeutic interventions such as angioplasty, stents, or bypass surgery, vascular smooth muscle cells (VSMCs) migrate from the media to the intima, resulting in intimal hyperplasia, restenosis, graft failure, or atherosclerosis. These proatherosclerotic factors also activate autophagy in VSMCs. However, the functional role of autophagy in vascular health and disease remains poorly understood. In the present study, we determined the role of autophagy in the regulation of VSMC migration. Autophagy activity in cultured human aortic smooth muscle cells (HASMCs) and mouse carotid arteries was measured by Western blot analysis of microtubule-associated protein 1 light chain 3 B (LC3B) and P62. The VSMC migration was determined by scratch wound assay and transwell migration assay. Ex vivo smooth muscle cell migration was determined using aortic ring assay. The in vivo SMC migration was examined by staining the carotid artery sections with smooth muscle alpha actin (alpha SMA) after carotid artery ligation. To examine the relationship between autophagy and neointimal hyperplasia, C57BL/6J mice were subjected to carotid artery ligation. Seven days after injury, protein levels of Atg5, Atg7, Beclin1, and LC3B drastically increased and remained higher in the injured arteries three weeks after the injury. In parallel with the activation of autophagy, vascular injury-induced neointimal hyperplasia as estimated by increased intima/media ratio. The en face staining of carotid artery showed that vascular injury enhanced alpha SMA staining in the intimal cells as compared with the sham operation. Treatment of HASMCs with platelet-derived growth factor (PDGF), one of the major factors for vascular remodeling in response to vascular injury, increased Atg7 and LC3 II protein levels and enhanced autophagosome formation. In addition, aortic ring assay demonstrated that PDGF treated aortic rings displayed an increase in neovessel formation compared with control rings. Whole mount staining for CD31 and alpha SMA in PDGF treated neovessels revealed that the neovessel structures were stained by alpha SMA but not CD31. In contrast, pharmacological and genetic suppression of autophagy inhibits VSMC migration. Especially, gene silencing of Atg7 inhibited VSMC migration induced by PDGF. Furthermore, three weeks after ligation, markedly decreased neointimal formation was found in mice treated with chloroquine, an inhibitor of autophagy. Quantitative morphometric analysis of the injured vessels revealed a marked reduction in the intima/media ratio in the mice treated with chloroquine. Conclusion: Autophagy activation increases VSMC migration while autophagy suppression inhibits VSMC migration. These findings suggest that autophagy suppression may be an important therapeutic strategy for atherosclerosis and intimal hyperplasia.

Keywords: autophagy, vascular smooth muscle cell, migration, neointimal formation

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Authors: Seunghwan Seo, Woo-Seok Lee, Ji-Sun Shin, Young Kyoung Rhee, Chang-Won Cho, Hee-Do Hong, Kyung-Tae Lee

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Doenjang, known as traditional Korean food, is product of a natural mixed fermentation process carried out by lactic acid bacteria (LAB). Lactobacillus sakei K040706 (K040706) has been accepted as the most populous LAB in over ripened doenjang. Recently, we reported the immunostimulatory effects of K040706 in RAW 264.7 macrophages and in a cyclophosphamide-induced mouse model. In this study, we investigated the ameliorative effects of K040706 in a dextran sulfate sodium (DSS)-induced colitis mouse model. We induced colitis using DSS in 5-week-ICR mice over 14 days with or without 0.1, 1 g/kg/day K040706 orally. The body weight, stool consistency, and gross bleeding were recorded for determination of the disease activity index (DAI). At the end of treatment, animals were sacrificed and colonic tissues were collected and subjected to histological experiments and myeloperoxidase (MPO) accumulation, cytokine determination, qRT-PCR and Western blot analysis. Results showed that K040706 significantly attenuated DSS-induced DAI score, shortening of colon length, enlargement of spleen and immune cell infiltrations into colonic tissues. Histological examinations indicated that K040706 suppressed edema, mucosal damage, and the loss of crypts induced by DSS. These results were correlated with the restoration of tight junction protein expression, such as, ZO-1 and occludin in K040706-treated mice. Moreover, K040706 reduced the abnormal secretions and mRNA expressions of pro-inflammatory mediators, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). DSS-induced mRNA expression of intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in colonic tissues was also downregulated by K040706 treatment. Furthermore, K040706 suppressed the protein and mRNA expression of toll-like receptor 4 (TLR4) and phosphorylation of NF-κB and signal transducer and activator of transcription 3 (STAT3). These results suggest that K040706 has an anti-colitic effect by inhibition of intestinal inflammatory responses in DSS-induced colitic mice.

Keywords: Lactobacillus sakei, NF-κB, STAT3, ulcerative colitis

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Authors: M. Reni Sagayaraj, S. Anand Gnana Selvam, R. Reynald Susainathan

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We analyze stochastic integrals associated with a mutation process. To be specific, we describe the cell population process and derive the differential equations for the joint generating functions for the number of mutants and their integrals in generating functions and their applications. We obtain first-order moments of the processes of the two-way mutation process in first-order moment structure of X (t) and Y (t) and the second-order moments of a one-way mutation process. In this paper, we obtain the limiting behaviour of the integrals in limiting distributions of X (t) and Y (t).

Keywords: stochastic integrals, single–server queue model, catastrophes, busy period

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Authors: Encarnación Álvarez, Rosa M. García-Fernández, Francisco J. Blanco-Encomienda, Juan F. Muñoz

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The European Union Survey on Income and Living Conditions (EU-SILC) is a popular survey which provides information on income, poverty, social exclusion and living conditions of households and individuals in the European Union. The EUSILC contains variables which may contain outliers. The presence of outliers can have an impact on the measures and indicators used by the EU-SILC. In this paper, we used data sets from various countries to analyze the presence of outliers. In addition, we obtain some indicators after removing these outliers, and a comparison between both situations can be observed. Finally, some conclusions are obtained.

Keywords: poverty line, headcount index, risk of poverty, skewness coefficient

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Authors: Theresia Dwi Hastuti, Kristiana Haryanti, Agustine Eva Maria Soekesi

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Today's family business continues to grow in big cities and in rural areas throughout Indonesia in line with the development of the business world and global competition. This study aims to analyze the effect of company value, leadership, and ownership succession on the financial performance of the family business. The research method was carried out quantitatively with multiple regression. The respondent amounted to 63 entrepreneurs. This study found that company value, leadership succession, relationships, and communication affect the financial performance of the family business.

Keywords: company value, family business, financial performance, leadership succession, ownership succession

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Authors: Daisuke Sagiya, Ren Kamioka

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South Africa has ratified the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) on 30th November 2007. In line with this, the Department of Social Development (DSD) revised the White Paper on the Rights of Persons with Disabilities (WPRPD), and the Cabinet approved it on 9th December 2015. The South African government is striving towards the elimination of poverty and inequality in line with UNCRPD and WPRPD. However, there are minimal programmes and services that have been provided to persons with disabilities in the rural community. In order to address current discriminative practices, disunity and limited self-representation in rural community, DSD in cooperation with the Japan International Cooperation Agency (JICA) is implementing the 'Project for the Promotion of Empowerment of Persons with Disabilities and Disability Mainstreaming' from May 2016 to May 2020. The project is targeting rural community as the project sites, namely 1) Collins Chabane municipality, Vhembe district, Limpopo and 2) Maluti-a-Phofung municipality, Thabo Mofutsanyana district, Free State. The project aims at developing good practices on Community-Based Inclusive Development (CBID) at the project sites which will be documented as a guideline and applied in other provinces in South Africa and neighbouring countries (Lesotho, Swaziland, Botswana, Namibia, Zimbabwe, and Mozambique). In cooperation with provincial and district DSD and local government, the project is currently implementing various community activities, for example: Establishment of Self-Help Group (SHG) of persons with disabilities and Peer Counselling in the villages, and will conduct Disability Equality Training (DET) and accessibility workshop in order to enhance the CBID in the project sites. In order to universalise good practices on CBID, the authors will explain lessons learned from the project by utilising the theories of disability and development studies and community psychology such as social model of disability, twin-track approach, empowerment theory, sense of community, helper therapy principle, etc. And the authors conclude that in order to realise social participation of persons with disabilities in rural community, CBID is a strong tool and persons with disabilities must play central roles in all spheres of CBID activities.

Keywords: community-based inclusive development, disability mainstreaming, empowerment of persons with disabilities, self-help group

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Authors: Javier Enciso-Benavides, Fredy Fabian, Carlos Castaneda, Luis Alfaro, Alex Choque, Aparicio Aguilar, Javier Enciso

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Background: The use of biomarkers in breast cancer diagnosis, therapy, and prognosis has gained increasing interest. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and may cause relapse. Therefore, due to the importance of diagnosis, therapy, and prognosis, several biomarkers that characterize CSCs have been identified; however, in treatment-naïve triple-negative breast tumors, there is an urgent need to identify new biomarkers and therapeutic targets. According to this, the aim of this study was to identify serum proteins associated with cancer stem cells and pluripotency in women with triple-negative breast tumors in order to subsequently identify a biomarker for this type of breast tumor. Material and Methods: Whole blood samples from 12 women with histopathologically diagnosed triple-negative breast tumors were used after obtaining informed consent from the patient. Blood serum was obtained by conventional procedure and frozen at -80ºC. Identification of cancer stem cell-associated proteins was performed by matrix-assisted laser desorption/ionisation-assisted laser desorption/ionisation mass spectrometry (MALDI-TOF MS), protein analysis was obtained using the AB Sciex TOF/TOF™ 5800 system (AB Sciex, USA). Sequences not aligned by ProteinPilot™ software were analyzed by Protein BLAST. Results: The following proteins related to pluripotency and cancer stem cells were identified by MALDI TOF/TOF mass spectrometry: A-chain, Serpin A12 [Homo sapiens], AIEBP [Homo sapiens], Alpha-one antitrypsin, AT {internal fragment} [human, partial peptide, 20 aa] [Homo sapiens], collagen alpha 1 chain precursor variant [Homo sapiens], retinoblastoma-associated protein variant [Homo sapiens], insulin receptor, CRA_c isoform [Homo sapiens], Hydroxyisourate hydrolase [Streptomyces scopuliridis], MUCIN-6 [Macaca mulatta], Alpha-actinin-3 [Chrysochloris asiatica], Polyprotein M, CRA_d isoform, partial [Homo sapiens], Transcription factor SOX-12 [Homo sapiens]. Recommendations: The serum proteins identified in this study should be investigated in the exosome of triple-negative breast cancer stem cells and in the blood serum of women without breast cancer. Subsequently, proteins found only in the blood serum of women with triple-negative breast cancer should be identified in situ in triple-negative breast cancer tissue in order to identify a biomarker to study the evolution of this type of cancer, or that could be a therapeutic target. Conclusions: Eleven cancer stem cell-related serum proteins were identified in 12 women with triple-negative breast cancer, of which MUCIN-6, retinoblastoma-associated protein variant, transcription factor SOX-12, and collagen alpha 1 chain are the most representative and have not been studied so far in this type of breast tumor. Acknowledgement: This work was supported by Proyecto CONCYTEC–Banco Mundial “Mejoramiento y Ampliacion de los Servicios del Sistema Nacional de Ciencia Tecnología e Innovacion Tecnologica” 8682-PE (104-2018-FONDECYT-BM-IADT-AV).

Keywords: triple-negative breast cancer, MALDI TOF/TOF MS, serum proteins, cancer stem cells

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Authors: Mohammad Nasb, Muhammad Rehan, Chen Hong

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Background Meniscus defects critically alter knee function and lead to degenerative changes. Regenerative medicine applications including stem cell transplantation have showed a promising efficacy in finding alternatives to overcome traditional treatment limitations. However, stem cell therapy remains limited due to the substantially reduced viability and inhibitory microenvironment. Since tissue growth and repair are under the control of biochemical and mechanical signals, several approaches have recently been investigated (e.g., low intensity pulsed ultrasound [LIPUS]) to promote the regeneration process. This study employed LIPUS to improve growth and osteogenic differentiation of mesenchymal stem cells derived from human embryonic stem cells to improve the regeneration of meniscus tissue. Methodology: The Mesenchymal stromal cells (MSCs) were transplanted into the epicenter of the injured meniscus in rabbits, which were randomized into two main groups: a treatment group (n=32 New Zealand rabbits) including 4 subgroups of 8 rabbits in each subgroup (LIPUS treatment, MSC treatment, LIPUS with MSC and control), and a second group (n=9) to track implanted cells and their progeny using green fluorescence protein (GFP). GFP consists of the MSC and LIPUS-MSC combination subgroups. Rabbits were then subjected to histological, immunohistochemistry, and MRI assessment. Results: The quantity of the newly regenerated tissue in the combination treatment group that had Ultrasound irradiation after mesenchymal stem cells were better at all end points. Likewise, Tissue quality scores were also greater in knees treated with both approaches compared with controls and single treatment at all end points, achieving significance at twelve and twenty-four weeks [p < 0.05], and [p = 0.008] at twelve weeks. Differentiation into type-I and II collagen-expressing cells were higher in the combination group at up to twenty-four weeks. Conclusions: the combination of mesenchymal stem cells and LIPUS showed greater adhering to the sites of meniscus injury, differentiate into cells resembling meniscal fibrochondrocytes, and improve both quality and quantity of meniscal regeneration.

Keywords: stem cells, regenerative medicine, osteoarthritis, knee

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Authors: Iliya Dimitrov Stoev, Benjamin Seelbinder, Elena Erben, Nicola Maghelli, Moritz Kreysing

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Despite the revolutionizing impact of optical tweezers in materials science and cell biology up to the present date, trapping has so far extensively relied on specific material properties of the probe and local heating has limited applications related to investigating dynamic processes within living systems. To overcome these limitations while maintaining high sensitivity, here we present a new optofluidic approach that can be used to gently trap microscopic particles and measure femtoNewton forces in a contact-free manner and with thermally limited precision.

Keywords: optofluidics, force measurements, microrheology, FLUCS, thermoviscous flows

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Authors: Kamolvara Sirisuksakulchai, Soamwadee Chaianansutcharit, Kazunori Sato

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Solid Oxide Fuel Cells (SOFCs) have been considered as one of the most efficient large unit power generators for household and industrial applications. The efficiency of an electronic cell depends mainly on the electrochemical reactions in the anode. The development of anode materials has been intensely studied to achieve higher kinetic rates of redox reactions and lower internal resistance. Recent studies have introduced an efficient cermet (ceramic-metallic) material for its ability in fuel oxidation and oxide conduction. This could expand the reactive site, also known as the triple-phase boundary (TPB), thus increasing the overall performance. In this study, a bimetallic catalyst Ni₀.₇₅Co₀.₂₅Oₓ was combined with Gd₀.₁Ce₀.₉O₁.₉₅ (GDC) to be used as a cermet anode (NiCo-GDC) for an anode-supported type SOFC. The synthesis of Ni₀.₇₅Co₀.₂₅Oₓ was carried out by ball milling NiO and Co3O4 powders in ethanol and calcined at 1000 °C. The Gd₀.₁Ce₀.₉O₁.₉₅ was prepared by a urea co-precipitation method. Precursors of Gd(NO₃)₃·6H₂O and Ce(NO₃)₃·6H₂O were dissolved in distilled water with the addition of urea and were heated subsequently. The heated mixture product was filtered and rinsed thoroughly, then dried and calcined at 800 °C and 1500 °C, respectively. The two powders were combined followed by pelletization and sintering at 1100 °C to form an anode support layer. The fabrications of an electrolyte layer and cathode layer were conducted. The electrochemical performance in H₂ was measured from 800 °C to 600 °C while for CH₄ was from 750 °C to 600 °C. The maximum power density at 750 °C in H₂ was 13% higher than in CH₄. The difference in performance was due to higher polarization resistances confirmed by the impedance spectra. According to the standard enthalpy, the dissociation energy of C-H bonds in CH₄ is slightly higher than the H-H bond H₂. The dissociation of CH₄ could be the cause of resistance within the anode material. The results from lower temperatures showed a descending trend of power density in relevance to the increased polarization resistance. This was due to lowering conductivity when the temperature decreases. The long-term stability was measured at 750 °C in CH₄ monitoring at 12-hour intervals. The maximum power density tends to increase gradually with time while the resistances were maintained. This suggests the enhanced stability from charge transfer activities in doped ceria due to the transition of Ce⁴⁺ ↔ Ce³⁺ at low oxygen partial pressure and high-temperature atmosphere. However, the power density started to drop after 60 h, and the cell potential also dropped from 0.3249 V to 0.2850 V. These phenomena was confirmed by a shifted impedance spectra indicating a higher ohmic resistance. The observation by FESEM and EDX-mapping suggests the degradation due to mass transport of ions in the electrolyte while the anode microstructure was still maintained. In summary, the electrochemical test and stability test for 60 h was achieved by NiCo-GDC cermet anode. Coke deposition was not detected after operation in CH₄, hence this confirms the superior properties of the bimetallic cermet anode over typical Ni-GDC.

Keywords: bimetallic catalyst, ceria-based SOFCs, methane oxidation, solid oxide fuel cell

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Authors: Rubens P. Costa, Marcelo A. Leigui de Oliveira

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The comprehension of features on the energy spectra, the chemical compositions, and the origins of Ultra-High Energy Cosmic Rays (UHECRs) - mainly atomic nuclei with energies above ~1.0 EeV (exa-electron volts) - are intrinsically linked to the problem of determining the magnitude of their deflections in cosmic magnetic fields on cosmological scales. In addition, as they propagate from the source to the observer, modifications are expected in their original energy spectra, anisotropy, and the chemical compositions due to interactions with low energy photons and matter. This means that any consistent interpretation of the nature and origin of UHECRs has to include the detailed knowledge of their propagation in a three-dimensional environment, taking into account the magnetic deflections and energy losses. The parameter space range for the magnetic fields in the universe is very large because the field strength and especially their orientation have big uncertainties. Particularly, the strength and morphology of the Extragalactic Magnetic Fields (EGMFs) remain largely unknown, because of the intrinsic difficulty of observing them. Monte Carlo simulations of charged particles traveling through a simulated magnetized universe is the straightforward way to study the influence of extragalactic magnetic fields on UHECRs propagation. However, this brings two major difficulties: an accurate numerical modeling of charged particles diffusion in magnetic fields, and an accurate numerical modeling of the magnetized Universe. Since magnetic fields do not cause energy losses, it is important to impose that the particle tracking method conserve the particle’s total energy and that the energy changes are results of the interactions with background photons only. Hence, special attention should be paid to computational effects. Additionally, because of the number of particles necessary to obtain a relevant statistical sample, the particle tracking method must be computationally efficient. In this work, we present an analysis of the propagation of ultra-high energy charged particles in the intergalactic medium. The EGMFs are considered to be coherent within cells of 1 Mpc (mega parsec) diameter, wherein they have uniform intensities of 1 nG (nano Gauss). Moreover, each cell has its field orientation randomly chosen, and a border region is defined such that at distances beyond 95% of the cell radius from the cell center smooth transitions have been applied in order to avoid discontinuities. The smooth transitions are simulated by weighting the magnetic field orientation by the particle's distance to the two nearby cells. The energy losses have been treated in the continuous approximation parameterizing the mean energy loss per unit path length by the energy loss length. We have shown, for a particle with the typical energy of interest the integration method performance in the relative error of Larmor radius, without energy losses and the relative error of energy. Additionally, we plotted the distance amplification from rectilinear propagation as a function of the traveled distance, particle's magnetic rigidity, without energy losses, and particle's energy, with energy losses, to study the influence of particle's species on these calculations. The results clearly show when it is necessary to use a full three-dimensional simulation.

Keywords: cosmic rays propagation, extragalactic magnetic fields, magnetic deflections, ultra-high energy

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Authors: A. Tamimi, S. Greatrex-White, A. Narayanasamy

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Background: Spirituality has been increasingly acknowledged in the nursing literature as an important element of holistic patient care. To date there have been numerous studies investigating the meaning of spirituality in Western cultures. Spirituality in Middle Eastern countries however remains under-researched. We will present a study which aimed to address this gap. Aim: The study aimed to explore how spirituality manifests in the lives of Jordanian End Stage Renal Failure (ESRF) patients. Methodology and Method: A hermeneutic phenomenological approach was adopted informed by the philosophy of Martin Heidegger. Participants (n=27) were recruited from four different dialysis units: in a public hospital, a private hospital, an educational hospital and a refugee’s hospital in Jordan. Data was collected through in-depth unstructured interviews. Data Analysis: Analysis was guided by the tenets of hermeneutic phenomenology namely: gaining immediate sense of what was said both during and after each interview, transcribing data verbatim, translating interviews into the English language, intensive reading and re-reading, seeking meaning units by line to line coding, developing situated structures (how spirituality was manifest in each text), developing a general structure from the individual situated structures (how the phenomenon ‘spirituality’ comes into being). Findings: Three major themes emerged from analysis: Religion, Relationships and Desperation. We will argue that a ‘secular’ concept of spirituality had no meaning for the participants in the study. Spirituality is fundamentally part of religion and vice versa. Discussion: The findings may have consequences for the use of spirituality in multi-cultural settings in Western countries. Additionally, findings highlighted an important emphasis on the practice of spirituality, often underestimated in previous literature for Arab-Muslim Jordanian patients. Conclusion: The study findings contribute to the existing gap in knowledge regarding how Arab-Muslim Jordanian ESRF patients experience spirituality during their illness. It provides valuable insights into the importance of spirituality for this patient group and suggests how nurses, educators and policy makers might help address ESRF patients’ spiritual needs and provide appropriate spiritual care. We suggest the findings may have relevance beyond the Jordanian context in educating nurses’ on the importance of appreciating the religious dimension of spirituality.

Keywords: spirituality, nursing, muslim, Jordan

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Authors: Andrey Lebedev, Ilya Dmitrenok, JooYoung Lee, Leonard Johard

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Top-k shortest path routing problem is an extension of finding the shortest path in a given network. Shortest path is one of the most essential measures as it reveals the relations between two nodes in a network. However, in many real world networks, whose diameters are small, top-k shortest path is more interesting as it contains more information about the network topology. Many variations to compute top-k shortest paths have been studied. In this paper, we apply an efficient top-k shortest distance routing algorithm to the link prediction problem and test its efficacy. We compare the results with other base line and state-of-the-art methods as well as with the shortest path. Then, we also propose a top-k distance based graph matching algorithm.

Keywords: graph matching, link prediction, shortest path, similarity

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Authors: Laura Boschis, Elena D. Ozzello, Enzo Mastromatteo

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Point of care diagnostic finds growing interest in medicine and agri-food because of faster intervention and prevention. EliChip is a microfluidic platform to perform Point of Care immunoenzymatic assay based on ready-to-use kits and a portable instrument to manage fluidics and read reliable quantitative results. Thanks to miniaturization, analyses are faster and more sensible than conventional ELISA. EliChip is one of the crucial assets of the Europen-founded Flamingo project for in-line measuring inflammatory markers.

Keywords: lab on chip, point of care, immunoenzymatic analysis, synovial arthritis

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