Search results for: breast cancer cell lines

Authors: T. Ghatauray, J. Ingram, P. Holborn

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The transition from a ‘carbon rich’ fossil fuel dependent to a ‘sustainable’ and ‘renewable’ hydrogen based society will see the deployment of hydrogen fuel cells (HFC) in transport applications and in the generation of heat and power for buildings, as part of a decentralised power network. Many deployments will be low power HFCs for domestic combined heat and power (CHP) and commercial ‘transportable’ HFCs for environmental situations, such as lighting and telephone towers. For broad commercialisation of small fuel cells to be achieved there needs to be significant confidence in their safety in both domestic and environmental applications. Low power HFCs are housed in protective steel enclosures. Standard enclosures have plain rectangular ventilation openings intended for thermal management of electronics and not the dispersion of a buoyant gas. Degradation of the HFC or supply pipework in use could lead to a low-level leak and a build-up of hydrogen gas in the enclosure. Hydrogen’s wide flammable range (4-75%) is a significant safety concern, with ineffective enclosure ventilation having the potential to cause flammable mixtures to develop with the risk of explosion. Mechanical ventilation is effective at managing enclosure hydrogen concentrations, but drains HFC power and is vulnerable to failure. This is undesirable in low power and remote installations and reliable passive ventilation systems are preferred. Passive ventilation depends upon buoyancy driven flow, with the size, shape and position of ventilation openings critical for producing predictable flows and maintaining low buoyant gas concentrations. With environmentally sited enclosures, ventilation openings with pressed horizontal and angled louvres are preferred to protect the HFC and electronics inside. There is an economic cost to adding louvres, but also a safety concern. A question arises over whether the use of pressed louvre vents impairs enclosure passive ventilation performance, when compared to same opening area plain vents. Comparison small enclosure (0.144m³) tests of same opening area pressed louvre and plain vents were undertaken. A displacement ventilation arrangement was incorporated into the enclosure with opposing upper and lower ventilation openings. A range of vent areas were tested. Helium (used as a safe analogue for hydrogen) was released from a 4mm nozzle at the base of the enclosure to simulate a hydrogen leak at leak rates from 1 to 10 lpm. Helium sensors were used to record concentrations at eight heights in the enclosure. The enclosure was otherwise empty. These tests determined that the use of pressed and angled louvre ventilation openings on the enclosure impaired the passive ventilation flow and increased helium concentrations in the enclosure. High-level stratified buoyant gas layers were also found to be deeper than with plain vent openings and were within the flammable range. The presence of gas within the flammable range is of concern, particularly as the addition of the fuel cell and electronics in the enclosure would further reduce the available volume and increase concentrations. The opening area of louvre vents would need to be greater than equivalent plain vents to achieve comparable ventilation flows or alternative schemes would need to be considered.

Keywords: enclosure, fuel cell, helium, hydrogen safety, louvre vent, passive ventilation

Procedia PDF Downloads 268

Authors: Dagmara A. Niedziela, Mark P. Murphy, Orla M. Keane, Finola C. Leonard

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Staphylococcus aureus is the most frequent cause of clinical and subclinical bovine mastitis in Ireland. Mastitis caused by S. aureus is often chronic and tends to recur after antibiotic treatment. This may be due to several virulence factors, including attributes that enable the bacterium to internalize into bovine mammary epithelial cells, where it may evade antibiotic treatment, or evade the host immune response. Four bovine-adapted lineages (CC71, CC97, CC151 and ST136) were identified among a collection of Irish S. aureus mastitis isolates. Genotypic variation of mastitis-causing strains may contribute to different presentations of the disease, including differences in milk somatic cell count (SCC), the main method of mastitis detection. The objective of this study was to investigate the influence of bacterial strain and lineage on host immune response, by employing cell culture methods in vitro as well as an in vivo infection model. Twelve bovine adapted S. aureus strains were examined for internalization into bovine mammary epithelial cells (bMEC) and their ability to induce an immune response from bMEC (using qPCR and ELISA). In vitro studies found differences in a variety of virulence traits between the lineages. Strains from lineages CC97 and CC71 internalized more efficiently into bovine mammary epithelial cells (bMEC) than CC151 and ST136. CC97 strains also induced immune genes in bMEC more strongly than strains from the other 3 lineages. One strain each of CC151 and CC97 that differed in their ability to cause an immune response in bMEC were selected on the basis of the above in vitro experiments. Fourteen first-lactation Holstein-Friesian cows were purchased from 2 farms on the basis of low SCC (less than 50 000 cells/ml) and infection free status. Seven cows were infected with 1.73 x 102 c.f.u. of the CC97 strain (Group 1) and another seven with 5.83 x 102 c.f.u. of the CC151 strain (Group 2). The contralateral quarter of each cow was inoculated with PBS (vehicle). Clinical signs of infection (temperature, milk and udder appearance, milk yield) were monitored for 30 days. Blood and milk samples were taken to determine bacterial counts in milk, SCC, white blood cell populations and cytokines. Differences in disease presentation in vivo between groups were observed, with two animals from Group 2 developing clinical mastitis and requiring antibiotic treatment, while one animal from Group 1 did not develop an infection for the duration of the study. Fever (temperature > 39.5⁰C) was observed in 3 animals from Group 2 and in none from Group 1. Significant differences in SCC and bacterial load between groups were observed in the initial stages of infection (week 1). Data is also being collected on cytokines and chemokines secreted during the course of infection. The results of this study suggest that a strain from lineage CC151 may cause more severe clinical mastitis, while a strain from lineage CC97 may cause mild, subclinical mastitis. Diversity between strains of S. aureus may therefore influence the clinical presentation of mastitis, which in turn may influence disease detection and treatment needs.

Keywords: Bovine mastitis, host immune response, host-pathogen interactions, Staphylococcus aureus

Procedia PDF Downloads 154

Authors: A. K. Tursunova, O. V. Chebonenko, A. Zh. Amirkulova, A. O. Abaildayev, O. A. Sapko, Y. M. Dyo, A. Sh. Utarbaeva

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Fusarium solani and its variants cause root and stem rot of plants. Dry rot is the most common disease of potato tubers during storage. The causative agents of fusariosis in contact with plants behave as antagonists, growth stimulants or parasites. The diversity of host-parasite relationships is explained by the parasite’s ability to produce a wide spectrum of biologically active compounds including toxins, enzymes, oligosaccharides, antibiotic substances, enniatins and gibberellins. Many of these metabolites contribute to the creation of compatible relations; others behave as elicitors, inducing various protective responses in plants. An important part of the strategy for developing plant resistance against pathogens is the activation of protein synthesis to produce protective ‘pathogenesis-related’ proteins. The family of PR-proteins known to confer the most protective response is chitinases (EC 3.2.1.14, Cht) and β-1,3-glucanases (EC 3.2.1.39, Glu). PR-proteins also include a large multigene family of peroxidases (EC 1.11.1.7, Pod), and increased activity of Pod and expression of the Pod genes leads to the development of resistance to a broad class of pathogens. Despite intensive research on the role of PR-proteins, the question of their participation in the mechanisms of formation of the F.solani–S.tuberosum pathosуstem is not sufficiently studied. Our aim was to investigate the effect of different classes of F. solani metabolites on the activity of chitinase, β-1,3-glucanases and peroxidases in tubers of Solanum tuberosum. Metabolite culture filtrate (CF) and cytoplasmic components were fractionated by extraction of the mycelium with organic solvents, salting out techniques, dialysis, column chromatography and ultrafiltration. Protein, lipid, carbohydrate and polyphenolic fractions of fungal metabolites were derived. Using enzymatic hydrolysis we obtained oligo glycans from fungal cell walls with different molecular weights. The activity of the metabolites was tested using potato tuber discs (d = 16mm, h = 5mm). The activity of PR-proteins of tubers was analyzed in a time course of 2–24 hours. The involvement of the analysed metabolites in the modulation of both early non-specific and late related to pathogenesis reactions was demonstrated. The most effective inducer was isolated from the CF (fraction of total phenolic compounds including naphtazarins). Induction of PR-activity by this fraction was: chitinase - 340-360%, glucanase - 435-450%, soluble forms of peroxidase - 400-560%, related forms of peroxidase - 215-237%. High-inducing activity was observed by the chloroform and acetonitrile extracts of the mycelium (induction of chitinase and glucanase activity was 176-240%, of soluble and bound forms of peroxidase - 190-400%). The fraction of oligo glycans mycelium cell walls of 1.2 kDa induced chitinase and β-1,3-glucanase to 239-320%; soluble forms and related peroxidase to 198-426%. Oligo glycans cell walls of 5-10 kDa had a weak suppressor effect - chitinase (21-25%) and glucanase (25-28%) activity; had no effect on soluble forms of peroxidase, but induced to 250-270% activity related forms. The CF polysaccharides of 8.5 kDa and 3.1 kDa inhibited synchronously the glucanase and chitinase specific response in step (after 24 hours at 42-50%) and the step response induced nonspecific peroxidase activity: soluble forms 4.8 -5.2 times, associated forms 1.4-1.6 times.

Keywords: fusarium solani, PR-proteins, peroxidase, solanum tuberosum

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Authors: William Abiodun Duyile

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It is common knowledge that marine food has always been found from the sea, energy can also be found underneath and, to a growing extent; other mineral resources have come from the sea spaces. It is the importance of the sea and the sea lines of communication to littoral nations that has made concepts such as sea power, naval power, etc., significant to them. The study relied on documentary data. The documentary data were sourced from government annual departmental reports, newspapers and correspondence. The secondary sources used were subjected to internal and external criticism for authentication, and then to textual and contextual analyses. The study found that the differential level of seamanship amongst states defined their relationship. It was sea power that gave some states an edge over the others. The study proves that over the ages sea power has been core to the development of States or Empires. The study found that the Nigerian Navy was centre to Nigeria’s conquest of the littoral areas of Biafra, like Bonny, Port-Harcourt, and Calabar; it was also an important turning point of the Nigerian civil war since by it Biafra became landlocked. The research was able to identify succinctly the Nigerian Navy’s contribution to the security and development of the Nigerian State.

Keywords: sea power, naval power, land locked states, warship

Procedia PDF Downloads 132

Authors: Betty Johanna Garzon Rozo, Jonathan Crook, Fernando Moreira

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Operational risk losses are heavy tailed and are likely to be asymmetric and extremely dependent among business lines/event types. We propose a new methodology to assess, in a multivariate way, the asymmetry and extreme dependence between severity distributions, and to calculate the capital for Operational Risk. This methodology simultaneously uses (i) several parametric distributions and an alternative mix distribution (the Lognormal for the body of losses and the Generalized Pareto Distribution for the tail) via extreme value theory using SAS®, (ii) the multivariate skew t-copula applied for the first time for operational losses and (iii) Bayesian theory to estimate new n-dimensional skew t-copula models via Markov chain Monte Carlo (MCMC) simulation. This paper analyses a newly operational loss data set, SAS Global Operational Risk Data [SAS OpRisk], to model operational risk at international financial institutions. All the severity models are constructed in SAS® 9.2. We implement the procedure PROC SEVERITY and PROC NLMIXED. This paper focuses in describing this implementation.

Keywords: operational risk, loss distribution approach, extreme value theory, copulas

Procedia PDF Downloads 592

Authors: T. A. Shahul Hameed, P. Predeep, Anju Iqbal, M. R. Baiju

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Research and development in organic photovoltaic cells and Organic Light Emitting Diodes have gained wider acceptance due to the advent of many advanced techniques to enhance the efficiency and operational hours. Here we report our work on design, simulation and characterizationracterize the bulk heterojunction organic photo cell and polymer light emitting diodes in different layer configurations using ATLAS, a licensed device simulation tool. Bulk heterojuction and multilayer devices were simulated for comparing their performance parameters.

Keywords: HOMO, LUMO, PLED, OPV

Procedia PDF Downloads 579

Authors: Zhongyang Sun, Shu Zhang

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In osteoblasts, L-type voltage sensitive calcium channels (LTCCs), especially the Cav1.2 LTCCs, play fundamental roles in cellular responses to external stimuli including both mechanical forces and hormonal signals. Several lines of evidence have revealed that the density of bone is increased and the resorption of bone is decreased when these calcium channels in osteoblasts are activated. And numerous studies have shown that mechanical loading promotes bone formation in the modeling skeleton, whereas removal of this stimulus in microgravity results in a reduction in bone mass. However, the effect of microgravity on LTCCs in osteoblasts is still unknown. The aim of this study was to determine whether microgravity exerts influence on LTCCs in osteoblasts and the possible mechanisms underlying. In this study, we demonstrate that simulated microgravity substantially inhibits LTCCs in osteoblast by suppressing the expression of Cav1.2. Then we show that the up-regulation of miR-103 is involved in the down-regulation of Cav1.2 expression and inhibition of LTCCs by simulated microgravity in osteoblasts. Our study provides a novel mechanism of simulated microgravity-induced adverse effects on osteoblasts, offering a new avenue to further investigate the bone loss caused by microgravity.

Keywords: L-type voltage sensitive calcium channels, Cav1.2, osteoblasts, microgravity

Procedia PDF Downloads 301

Authors: Lalitchandra J. Shah, Katarzyna Bialek, Melinda L. Clarke, Jessica L. Jansson

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Handwriting is essential to academic success; however, the current literature is limited in the identification of pre-handwriting skills. The purpose of this study was to identify the pre-handwriting skills, which occupational therapy practitioners deem important to handwriting success, as well as those which aid in intervention planning. The online survey instrument consisted of 33 questions that assessed various skills related to the development of handwriting, as well as captured demographic information. Both occupational therapists and occupational therapy assistants were included in the survey study. The survey found that the respondents were in agreement that purposeful scribbling, the ability of a child to copy (vertical/horizontal lines, circle, squares, and triangles), imitating an oblique cross, cognitive skills (attention, praxis, self-regulation, sequencing), grasp patterns, hand dominance, in hand manipulation skills (shift, translation, rotation), bilateral integration, stabilization of paper, crossing midline, and visual perception were important indicators of handwriting readiness. The results of the survey support existing research regarding the skills necessary for the successful development of handwriting in children.

Keywords: development, handwriting, occupational therapy, visual perceptual skills

Procedia PDF Downloads 346

Authors: Mahmoodreza Tahamtan

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Malignant surface epithelial ovarian tumors(SEOT) account for approximately 90% of primary ovarian cancer. We evaluate the immunohistochemical expression of WT1 protein among different histologic subtypes of SEOT. Immunohistochemistry for WT1 was done on 35 serous cystadenocarcinomas, 9 borderline serous tumors. A tumor was considered negative if < 1% of tumor cells were stained.Positive reactions were graded as follows:1+,1%-24%; 2+,25%-49%; 3+,50%-74%; 4+,75%-100%. Of the 35 cases of ovarian serous cystadenocarcinoma 30(85.7%)were diffusely positive(3+,4+),4 showed reactivity of < 50% of the tumor cells(1+,2+) and one were negative. All 9 borderline serous tumors showed immunoreactivity with WT1. WT1 is a good marker to distinguish primary ovarian serous carcinomas from other surface epithelial tumors.

Keywords: WT1, ovary, malignant, epithelial tumors

Procedia PDF Downloads 94

Authors: Jalil ur Rehman, Ramesh C. Tailor, Muhammad Isa Khan, Jahnzeeb Ashraf, Muhammad Afzal, Geofferry S. Ibbott

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Purpose: The purpose of this analysis was to investigate dose distribution of different techniques (3D-CRT, IMRT and VMAT) of head and neck cancer using 3-dimensional dosimeter called PRESAGETM Dosimeter. Materials and Methods: Computer tomography (CT) scans of radiological physics center (RPC) head and neck anthropomorphic phantom with both RPC standard insert and PRESAGETM insert were acquired separated with Philipp’s CT scanner and both CT scans were exported via DICOM to the Pinnacle version 9.4 treatment planning system (TPS). Each plan was delivered twice to the RPC phantom first containing the RPC standard insert having TLD and film dosimeters and then again containing the Presage insert having 3-D dosimeter (PRESAGETM) by using a Varian True Beam linear accelerator. After irradiation, the standard insert including point dose measurements (TLD) and planar Gafchromic® EBT film measurement were read using RPC standard procedure. The 3D dose distribution from PRESAGETM was read out with the Duke Midsized optical scanner dedicated to RPC (DMOS-RPC). Dose volume histogram (DVH), mean and maximal doses for organs at risk were calculated and compared among each head and neck technique. The prescription dose was same for all head and neck radiotherapy techniques which was 6.60 Gy/friction. Beam profile comparison and gamma analysis were used to quantify agreements among film measurement, PRESAGETM measurement and calculated dose distribution. Quality assurances of all plans were performed by using ArcCHECK method. Results: VMAT delivered the lowest mean and maximum doses to organ at risk (spinal cord, parotid) than IMRT and 3DCRT. Such dose distribution was verified by absolute dose distribution using thermoluminescent dosimeter (TLD) system. The central axial, sagittal and coronal planes were evaluated using 2D gamma map criteria(± 5%/3 mm) and results were 99.82% (axial), 99.78% (sagital), 98.38% (coronal) for VMAT plan and found the agreement between PRESAGE and pinnacle was better than IMRT and 3D-CRT plan excludes a 7 mm rim at the edge of the dosimeter. Profile showed good agreement for all plans between film, PRESAGE and pinnacle and 3D gamma was performed for PTV and OARs, VMAT and 3DCRT endow with better agreement than IMRT. Conclusion: VMAT delivered lowered mean and maximal doses to organs at risk and better PTV coverage during head and neck radiotherapy. TLD, EBT film and PRESAGETM dosimeters suggest that VMAT was better for the treatment of head and neck cancer than IMRT and 3D-CRT.

Keywords: RPC, 3DCRT, IMRT, VMAT, EBT2 film, TLD, PRESAGETM

Procedia PDF Downloads 381

Authors: Katalin Bodor, Zsolt Bodor, Robert Szep

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The particulate matter (PM) smaller than 2.5 μm are less studied due to the limited availability of PM₂.₅, and less information is available on the health effects attributable to PM₁₀ in Central-Eastern Europe. The objective of the current study was to assess the human health risk and characterize the spatial and temporal variation of PM₂.₅ and PM₁₀ in eight Romanian regions between the 2009-2018 and. The PM concentrations showed high variability over time and spatial distribution. The highest concentration was detected in the Bucharest region in the winter period, and the lowest was detected in West. The relative risk caused by the PM₁₀ for all-cause mortality varied between 1.017 (B) and 1.025 (W), with an average 1.020. The results demonstrate a positive relative risk of cardiopulmonary and lung cancer disease due to exposure to PM₂.₅ on the national average 1.26 ( ± 0.023) and 1.42 ( ± 0.037), respectively.

Keywords: PM₂.₅, PM₁₀, relative risk, health effect

Procedia PDF Downloads 157

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

Procedia PDF Downloads 172

Authors: Witthaya Mekhum, Napasri Suwanajote, Isara Sangprasert

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This research on logo design of pajamas, OTOP product of Sainoi community, Sainoi district, Nonthanuri Province is a participatory action research aiming to find the logo for pajamas, an OTOP product of Sainoi community. Sample of this research is 50 local residents from Sainoi community in Sainoi district, Nonthanuri Province. The questionnaire consisted of 4 main parts. Part 1: factors that influence the decisions of consumers; Part 2: characteristics of the materials used in the design; Part 3: attitude assessment and needs of consumers about logo designing to develop marketing channels; Part 4: suggestions. Interviews were conducted. For data analysis, checklist items were analyzed with frequency and percentage. Open-end items were analyzed by summarizing and using ratio scale and mean and standard deviation. The research results showed that the design, cutting and fabric affect the decision of the consumers. They want design to be decent and beautiful. Illustrations used in graphic design logos should be Lines. Fonts should be English letters and the color of the font should be the same color.

Keywords: design, logo, OTOP product, pajamas

Procedia PDF Downloads 264

Authors: Pierobon Enrico, Missiaggia Marta, Castelluzzo Michele, Tommasino Francesco, Ricci Leonardo, Scifoni Emanuele, Vincezo Monaco, Boscardin Maurizio, La Tessa Chiara

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Clinical outcomes collected over the past three decades have suggested that ion therapy has the potential to be a treatment modality superior to conventional radiation for several types of cancer, including recurrences, as well as for other diseases. Although the results have been encouraging, numerous treatment uncertainties remain a major obstacle to the full exploitation of particle radiotherapy. To overcome therapy uncertainties optimizing treatment outcome, the best possible radiation quality description is of paramount importance linking radiation physical dose to biological effects. Microdosimetry was developed as a tool to improve the description of radiation quality. By recording the energy deposition at the micrometric scale (the typical size of a cell nucleus), this approach takes into account the non-deterministic nature of atomic and nuclear processes and creates a direct link between the dose deposited by radiation and the biological effect induced. Microdosimeters measure the spectrum of lineal energy y, defined as the energy deposition in the detector divided by most probable track length travelled by radiation. The latter is provided by the so-called “Mean Chord Length” (MCL) approximation, and it is related to the detector geometry. To improve the characterization of the radiation field quality, we define a new quantity replacing the MCL with the actual particle track length inside the microdosimeter. In order to measure this new quantity, we propose a two-stage detector consisting of a commercial Tissue Equivalent Proportional Counter (TEPC) and 4 layers of Low Gain Avalanche Detectors (LGADs) strips. The TEPC detector records the energy deposition in a region equivalent to 2 um of tissue, while the LGADs are very suitable for particle tracking because of the thickness thinnable down to tens of micrometers and fast response to ionizing radiation. The concept of HDM has been investigated and validated with Monte Carlo simulations. Currently, a dedicated readout is under development. This two stages detector will require two different systems to join complementary information for each event: energy deposition in the TEPC and respective track length recorded by LGADs tracker. This challenge is being addressed by implementing SoC (System on Chip) technology, relying on Field Programmable Gated Arrays (FPGAs) based on the Zynq architecture. TEPC readout consists of three different signal amplification legs and is carried out thanks to 3 ADCs mounted on a FPGA board. LGADs activated strip signal is processed thanks to dedicated chips, and finally, the activated strip is stored relying again on FPGA-based solutions. In this work, we will provide a detailed description of HDM geometry and the SoC solutions that we are implementing for the readout.

Keywords: particle tracking, ion therapy, low gain avalanche diode, tissue equivalent proportional counter, microdosimetry

Procedia PDF Downloads 164

Authors: Maedeh Gharazi

Abstract:

Distinguishing proof of entrepreneurial open doors in the field of nutrition counseling is a focal issue in utilizing nutrition experts and addressing the needs of patients with chronic diseases better. To this end, this review has been directed keeping in mind the end goal to investigate the supply and interest patterns of diabetes sustenance advising as a fundamental stride toward recognizing the entrepreneurial open doors for nutrition advisors in Tehran, Iran. To execute this expressive overview concentrate on, a survey in light of Likert scale was sent via email to 100 dynamic experts in the field of nutrition counseling services in Tehran, of whom 52 reacted to its inquiries. At that point, the mean estimations of members' reactions were ascertained utilizing SPSS programming and contrasted to each other. The outcome acquired in view of members' reactions uncovered that the requirement for "healthful guiding as a treatment group" was basically not met in diverse age, training and salary gatherings of diabetic patients. Along these lines, nutrition counseling as a treatment group can be considered as a suitable field for entrepreneurial exercises.

Keywords: nutrition counseling, chronic diseases, diabetes, likert scale, SPSS programming

Procedia PDF Downloads 335

Authors: Vinai K. Singh

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In Neural Network-based Learning techniques, there are several models of Convolutional Networks. Whenever the methods are deployed with large datasets, only then can their applicability and appropriateness be determined. Clinical and pathological pictures of lobular carcinoma are thought to exhibit a large number of random formations and textures. Working with such pictures is a difficult problem in machine learning. Focusing on wet laboratories and following the outcomes, numerous studies have been published with fresh commentaries in the investigation. In this research, we provide a framework that can operate effectively on raw photos of various resolutions while easing the issues caused by the existence of patterns and texturing. The suggested approach produces very good findings that may be used to make decisions in the diagnosis of cancer.

Keywords: lobular carcinoma, convolutional neural networks (CNN), deep learning, histopathological imagery scans

Procedia PDF Downloads 130

Authors: L. Korpinen, P. Taskinen, P. Rautio

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This study aimed to describe procedures that we developed to use in the quantitative, bone-specific SPECT/CT at our hospital. Our procedures included the following questions for choosing imaging protocols, which were based on a clinical doctor's referral: (1) Is she/he a cancer patient or not? (2) Are there any indications of inflammatory rheumatoid arthritis? We performed about 1,106 skeletal scintigraphies over two years. About 394 patients were studied with quantitative bone-specific single-photon emission computed tomography/computerized tomography (SPECT/CT) (i.e., about 36% of all bone scintigraphies). Approximately 64% of the patients were studied using the conventional Anterior-Posterior/Posterior-Anterior imaging. Our procedure has improved efficiency and decreased cycle times.

Keywords: skeletal scintigraphy, SPECT/CT, imaging, procedure

Procedia PDF Downloads 144

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 151

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

Procedia PDF Downloads 161

Authors: Chang Liang, Weizhi Gong, Yan Zhang

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Purpose: Hepatocellular carcinoma (HCC) is a malignant tumor with a high mortality rate and poor prognosis worldwide. Murine double minute 2 (MDM2) regulates the tumor suppressor p53, increasing cancer risk and accelerating tumor progression. Speckle-type POX virus and zinc finger protein (SPOP), a key of subunit of Cullin-Ring E3 ligase, inhibits tumor genesis and progression by the ubiquitination of its downstream substrates. This study aimed to clarify whether SPOP and MDM2 are mutually regulated in HCC and the correlation between SPOP and MDM2 and the prognosis of HCC patients. Methods: First, the expression of SPOP and MDM2 in HCC tissues were detected by TCGA database. Then, 53 paired samples of HCC tumor and adjacent tissues were collected to evaluate the expression of SPOP and MDM2 using immunohistochemistry. Chi-square test or Fisher’s exact test were used to analyze the relationship between clinicopathological features and the expression levels of SPOP and MDM2. In addition, Kaplan‒Meier curve analysis and log-rank test were used to investigate the effects of SPOP and MDM2 on the survival of HCC patients. Last, the Multivariate Cox proportional risk regression model analyzed whether the different expression levels of SPOP and MDM2 were independent risk factors for the prognosis of HCC patients. Results: Bioinformatics analysis revealed the low expression of SPOP and high expression of MDM2 were related to worse prognosis of HCC patients. The relationship between the expression of SPOP and MDM2 and tumor stem-like features showed an opposite trend. The immunohistochemistry showed the expression of SPOP protein was significantly downregulated while MDM2 protein significantly upregulated in HCC tissue compared to that in para-cancerous tissue. Tumors with low SPOP expression were related to worse T stage and Barcelona Clinic Liver Cancer (BCLC) stage, but tumors with high MDM2 expression were related to worse T stage, M stage, and BCLC stage. Kaplan–Meier curves showed HCC patients with high SPOP expression and low MDM2 expression had better survival than those with low SPOP expression and high MDM2 expression (P < 0.05). A multivariate Cox proportional risk regression model confirmed that a high MDM2 expression level was an independent risk factor for poor prognosis in HCC patients (P <0.05). Conclusion: The expression of SPOP protein was significantly downregulated, while the expression of MDM2 significantly upregulated in HCC. The low expression of SPOP and high expression. of MDM2 were associated with malignant progression and poor prognosis of HCC patients, indicating a potential therapeutic target for HCC patients.

Keywords: hepatocellular carcinoma, murine double minute 2, speckle-type POX virus and zinc finger protein, ubiquitination

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Authors: K. A.Veselova, N. V.Gromova, I. N.Antonova, I. N. Kalakutskii

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There are many diseases and incidents that may result facial defects and deformities: cancer, trauma, burns, congenital anomalies, and autoimmune diseases. In some cases, patient may acquire atypically extensive facial defect, including more than one anatomical region or, by contrast, atypically small defect (e.g. partial auricular defect). The anaplastology gives us opportunity to help patient with facial disfigurement in cases when plastic surgery is contraindicated. Using of implant retention for facial prosthesis is strongly recommended because improves both aesthetic and functional results and makes using of the prosthesis more comfortable. Prostheticly oriented fixture position is extremely important for aesthetic and functional long-term result; however, the optimal site for fixture placement is not clear in cases with atypical configuration of facial defect. The objective of this report is to demonstrate challenges in fixture position determination we have faced with and offer the solution. In this report, four cases of implant-supported facial prosthesis are described. Extra-oral implants with four millimeter length were used in all cases. The decision regarding the quantity of surgical stages was based on anamnesis of disease. Facial prostheses were manufactured according to conventional technique. Clinical and technological difficulties and mistakes are described, and prostheticly oriented approach for determination of fixture position is demonstrated. The case with atypically large combined orbital and nasal defect resulting after arteriovenous malformation is described: the correct positioning of artificial eye was impossible due to wrong position of the fixture (with suprastructure) located in medial aspect of supraorbital rim. The suprastructure was unfixed and this fixture wasn`t used for retention in order to achieve appropriate artificial eye placement and better aesthetic result. In other case with small partial auricular defect (only helix and antihelix were absent) caused by squamoized cell carcinoma T1N0M0 surgical template was used to avoid the difficulties. To achieve the prostheticly oriented fixture position in case of extremely small defect the template was made on preliminary cast using vacuum thermoforming method. Two radiopaque markers were incorporated into template in preferable for fixture placement positions taking into account future prosthesis configuration. The template was put on remaining ear and cone-beam CT was performed to insure, that the amount of bone is enough for implant insertion in preferable position. Before the surgery radiopaque markers were extracted and template was holed for guide drill. Fabrication of implant-retained facial prostheses gives us opportunity to improve aesthetics, retention and patients’ quality of life. But every inaccuracy in planning leads to challenges on surgery and prosthetic stages. Moreover, in cases with atypically small or extended facial defects prostheticly oriented approach for determination of fixture position is strongly required. The approach including surgical template fabrication is effective, easy and cheap way to avoid mistakes and unpredictable result.

Keywords: anaplastology, facial prosthesis, implant-retained facial prosthesis., maxillofacil prosthese

Procedia PDF Downloads 102

Authors: Sophio Kobauri, Tengiz Kantaria, Temur Kantaria, David Tugushi, Nina Kulikova, Ramaz Katsarava

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Polymeric disperse systems such as nanoparticles (NPs) are of high interest for numerous applications in contemporary medicine and nanobiotechnology to a considerable potential for treatment of many human diseases. The important technological advantages of NPs usage as drug carriers (nanocontainers) are their high stability, high carrier capacity, feasibility of encapsulation of both hydrophilic or hydrophobic substances, as well as a high variety of possible administration routes, including oral application and inhalation. NPs can also be designed to allow controlled (sustained) drug release from the matrix. These properties of NPs enable improvement of drug bioavailability and might allow drug dosage decrease. The targeted and controlled administration of drugs using NPs might also help to overcome drug resistance, which is one of the major obstacles in the control of epidemics. Various degradable and non-degradable polymers of both natural and synthetic origin have been used for NPs construction. One of the most promising for the design of NPs are amino acid-based biodegradable polymers (AABBPs) which can clear from the body after the fulfillment of their function. The AABBPs are composed of naturally occurring and non-toxic building blocks such as α-amino acids, fatty diols and dicarboxylic acids. The particles designed from these polymers are expected to have an improved bioavailability along with a high biocompatibility. The present work deals with a systematic study of the preparation of NPs by cost-effective polymer deposition/solvent displacement method using AABBPs. The influence of the nature and concentration of surfactants, concentration of organic phase (polymer solution), and the ratio organic phase/inorganic(water) phase, as well as of some other factors on the size of the fabricated NPs have been studied. It was established that depending on the used conditions the NPs size could be tuned within 40-330 nm. At the next step of this research was carried out an evaluation of biocompability and bioavailability of the synthesized NPs using a stable human cell culture line – A549. It was established that the obtained NPs are not only biocompatible but they stimulate the cell growth.

Keywords: amino acids, biodegradable polymers, bioavailability, nanoparticles

Procedia PDF Downloads 293

Authors: Kelvin Datonye Bob-Manuel

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The shipping industry has begun to seriously look at ways of reducing fossil fuel consumption so that current reserves can last longer and operate their ships in a more environmentally friendly way. The concept of Green Shipping or Sustainable Shipping with the use of alternative fuels is now becoming an important issue for ship owners, shipping lines and ship builders globally. This paper provides a critical review of the performance of biodiesel and natural gas-fuelled diesel engines for shipboard application. The emission reduction technique included the use of either neat or emulsified rapeseed methyl ester (RME) for pilot ignition and the emission of NOx, CO2 and SOx were measured at engine speed range of 500 - 1500 r/min. The NOx concentrations were compared with the regulated IMO MARPOL73/78, Annex VI, Tiers I, II, III and United States Environmental Protection Agency (US-EPA) standard. All NOx emissions met Tier I and II levels and the EPA standard for the minimum specification of category 1 engines at higher speed but none met the MARPOL Tier III limit which is for designated Emission Control Areas (ECAs). No trace of soot and SOx emission were observed.

Keywords: dual-fuel, biodiesel, natural gas, NOx, SOx, MARPOL 73/78 Annex VI. USEPA Tier 3, EURO V &VI

Procedia PDF Downloads 408

Authors: Mirza Ahsan Baig, Paul Evans

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Due to the high demand for automobiles, manufacturers have to run their production lines non-stop for long periods. At such a scale, unplanned downtime could cost up to $50 billion annually. Improper training of new hires could lead to safety issues causing unplanned downtimes. The project developed a virtual reality simulation that could train personnel for key operations on an automobile manufacturing floor, reducing the risk of unplanned downtime while eliminating any disruption (due to training) on the assembly line. An automation firm sponsored it to explore the possibilities the likes of Jaguar and BMW are yet to achieve! The project was inspired by Bentley, the only company that succeeded in simulation training scenarios within virtual space. The project aims to inspire other significant firms to do the same. It was increasing employee safety, eliminating downtimes, and improving efficiency. The developed prototype uncovered various limitations within existing simulation providers and was able to simulate state-of-the-art training scenarios. It also explored the possibility of a multiuser interface and resolved complex issues such as lack of movement space within the training area.

Keywords: virtual reality, scenario training, limited movement, multiuser

Procedia PDF Downloads 81

Authors: Azad Khalid, Sifa Dogan

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Because of its persistence in conventional treatment plants and broad prevalence in water bodies, the pharmaceutical chemical carbamazepine (CBZ) has been suggested as an anthropogenic marker to evaluate water quality. This study provides a thorough examination of the origins and occurrences of CBZ in water bodies, as well as the drug's toxicological effects and laws. Given CBZ's well-documented negative consequences on the human body when used medicinally, cautious monitoring in water is advised. CBZ residues in drinking water may enter embryos and newborns via intrauterine exposure or breast-feeding, causing congenital abnormalities and/or neurodevelopmental issues over time. The insufficiency of solo solutions was shown after an in-depth technical study of traditional and sophisticated treatment technologies. Nanofiltration and reverse osmosis membranes are more successful at removing CBZ than traditional activated sludge and membrane bioreactor techniques. Recent research has shown that severe chemical cleaning, which is essential to prevent membrane fouling, may lower long-term removal efficiency. Furthermore, despite the efficacy of activated carbon adsorption and advanced oxidation processes, a few issues such as chemical cost and activated carbon renewal must be carefully examined. Individual technology constraints lead to the benefits of combined and hybrid systems, namely the heterogeneous advanced oxidation process.

Keywords: carbamazepine, occurrence, toxicity, conventical treatment, advanced oxidation process (AOPs)

Procedia PDF Downloads 90

Authors: Anil Kumar, Rajnish Kaur, Mateusz Czyzycki, Alessandro Migilori, Andreas Germanos Karydas, Sanjiv Puri

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The radiative decay of Li(i=1-3) sub-shell vacancies produced through photoionization results in production of the characteristic emission spectrum comprising several X-ray lines, whereas non-radiative vacancy decay results in Auger electron spectrum. Accurate reliable data on the Li(i=1-3) sub-shell X-ray production (XRP) cross sections is of considerable importance for investigation of atomic inner-shell ionization processes as well as for quantitative elemental analysis of different types of samples employing the energy dispersive X-ray fluorescence (EDXRF) analysis technique. At incident photon energies in vicinity of the absorption edge energies of an element, the many body effects including the electron correlation, core relaxation, inter-channel coupling and post-collision interactions become significant in the photoionization of atomic inner-shells. Further, in case of compounds, the characteristic emission spectrum of the specific element is expected to get influenced by the chemical environment (coordination number, oxidation state, nature of ligand/functional groups attached to central atom, etc.). These chemical effects on L X-ray fluorescence parameters have been investigated by performing the measurements at incident photon energies much higher than the Li(i=1-3) sub-shell absorption edge energies using EDXRF spectrometers. In the present work, the cross sections for production of the Lk(k= γ2,3, γ4) X-rays have been measured for some compounds of 66Dy, namely, Dy2O3, Dy2(CO3)3, Dy2(SO4)3.8H2O, DyI2 and Dy metal by tuning the incident photon energies few eV above the L1 absorption-edge energy in order to investigate the influence of chemical effects on these cross sections in presence of the many body effects which become significant at photon energies close to the absorption-edge energies. The present measurements have been performed under vacuum at the IAEA end-station of the X-ray fluorescence beam line (10.1L) of ELETTRA synchrotron radiation facility (Trieste, Italy) using self-supporting pressed pellet targets (1.3 cm diameter, nominal thicknesses ~ 176 mg/cm2) of 66Dy compounds (procured from Sigma Aldrich) and a metallic foil of 66Dy (nominal thickness ~ 3.9 mg/cm2, procured from Good Fellow, UK). The present measured cross sections have been compared with theoretical values calculated using the Dirac-Hartree-Slater(DHS) model based fluorescence and Coster-Kronig yields, Dirac-Fock(DF) model based X-ray emission rates and two sets of L1 sub-shell photoionization cross sections based on the non-relativistic Hartree-Fock-Slater(HFS) model and those deduced from the self-consistent Dirac-Hartree-Fock(DHF) model based total photoionization cross sections. The present measured XRP cross sections for 66Dy as well as for its compounds for the L2,3 and L4 X-rays, are found to be higher by ~14-36% than the two calculated set values. It is worth to be mentioned that L2,3 and L4 X-ray lines are originated by filling up of the L1 sub-shell vacancies by the outer sub-shell (N2,3 and O2,3) electrons which are much more sensitive to the chemical environment around the central atom. The present observed differences between measured and theoretical values are expected due to combined influence of the many-body effects and the chemical effects.

Keywords: chemical effects, L X-ray production cross sections, Many body effects, Synchrotron radiation

Procedia PDF Downloads 124

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

Procedia PDF Downloads 323

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

Procedia PDF Downloads 183

Authors: Liliana M. Marinelli, Cristina T. Varanese

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In the last few years, students from higher education have difficulties in grasping mathematical concepts which support physical matters, especially those in the first years of this education. Classical Physics teaching turns to be complex when students are not able to make use of mathematical tools which lead to the conceptual structure of Physics. When derivation and integration rules are not used or developed in parallel with other disciplines, the physical meaning that we attempt to convey turns to be complicated. Due to this fact, it could be of great use to see the Classical Mechanics from an axiomatic approach, where the correspondence rules give physical meaning, if we expect students to understand concepts clearly and accurately. Using the Minkowski point of view adapted to a two-dimensional space and time where vectors, matrices, and straight lines (worked from an affine space) give mathematical and physical rigorosity even when it is more abstract. An interesting option would be to develop the disciplinary contents from an axiomatic version which embraces the Classical Mechanics as a particular case of Relativistic Mechanics. The observation about the increase in the difficulties stated by students in the first years of education allows this idea to grow as a possible option to improve performance and understanding of the concepts of this subject.

Keywords: axioms, classical physics, physical concepts, relativity

Procedia PDF Downloads 299

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

Procedia PDF Downloads 310