Search results for: exponential expression profile

Authors: Samia Dahmani

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The research investigated the process and outcomes of an ongoing project, “Den Grønne Rute”: a network of recreational rooms to be implemented throughout a former vulnerable neighborhood: Trekanten, in the city of Holstebro in Denmark. The aim of the project is to better integrate Trekanten in the city and which initiated reflections upon the (dis)connection and the integration in relation to urban planning and city management, as well as the extent to which the project considers diversity since Holstebro is a growing multicultural city. With this research, it was first verified if Trekanten is splintered from Holstebro city, and secondly if planning for diversity, by engaging people in the process via place-making approaches, can help redress the disconnection between the neighborhood and the rest of the city. More specifically, the paper aims at exploring the role of place-making “Den Grønne Rute” in Trekanten in promoting planning for diversity and reassembling the splintering in the city. The theoretical and conceptual framework served to analyze the relationship between the splintering urbanism concept and the community involvement’s role for an inclusive process. The field study examines the detachment between Trekanten and Holstebro and the extent to which the project can overcome the disconnection. Methodologically a mix-methods approach was adopted where two semi-structured interviews, a focus group, and an online survey were conducted. Contrary to prior assumptions, the results showed that not only is Trekanten splintered from the city, but also the city is greatly disconnected from Trekanten, and hence Holstebro is a splintered city. The surprise was that Trekanten is moreover inner-splintered. The splintering urbanism accordingly has different dimensions. Even though the project’s design seemed to incorporate diverse ages and groups of people, its process lacks an understanding of the diversity’s relevance in promoting inclusiveness. In fact, the analysis revealed socio-cultural and psychological splintering. Since place-making, as a collaborative approach in planning, is itself an expression of diversity (since it brings differences into play), reconsidering diversity within the process by engaging people at the early sages of planning was recommended. Another suggestion was not to limit the project to a destination but more as an experience to remember and a story to tell. Only by bringing people together in re-imagining the place, can Trekanten reassemble with Holstebro and vice versa. The aim with the research was to add a new perspective to the splintering urbanism and planning for diversity so to advance place-making as an approach in promoting the latter and redressing the former.

Keywords: the splintering urbanism, placemaking, planning for diversity, den grønne rute, trekanten, holstebro

Procedia PDF Downloads 88

Authors: Mohamed Dhouibi, Bogdan Stirbu, Chabotier André, Marc Pirlot

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Internal barrel wear is a major factor affecting the performance of small caliber guns in their different life phases. Wear analysis is, therefore, a very important process for understanding how wear occurs, where it takes place, and how it spreads with the aim on improving the accuracy and effectiveness of small caliber weapons. This paper discusses the measurement and analysis of combustion chamber wear for a small-caliber gun using a Coordinate Measuring Machine (CMM). Initially, two different NATO small caliber guns: 5.56x45mm and 7.62x51mm, are considered. A Micura Zeiss Coordinate Measuring Machine (CMM) equipped with the VAST XTR gold high-end sensor is used to measure the inner profile of the two guns every 300-shot cycle. The CMM parameters, such us (i) the measuring force, (ii) the measured points, (iii) the time of masking, and (iv) the scanning velocity, are investigated. In order to ensure minimum measurement error, a statistical analysis is adopted to select the reliable CMM parameters combination. Next, two measurement strategies are developed to capture the shape and the volume of each gun chamber. Thus, a task-specific measurement uncertainty (TSMU) analysis is carried out for each measurement plan. Different approaches of TSMU evaluation have been proposed in the literature. This paper discusses two different techniques. The first is the substitution method described in ISO 15530 part 3. This approach is based on the use of calibrated workpieces with similar shape and size as the measured part. The second is the Monte Carlo simulation method presented in ISO 15530 part 4. Uncertainty evaluation software (UES), also known as the Virtual Coordinate Measuring Machine (VCMM), is utilized in this technique to perform a point-by-point simulation of the measurements. To conclude, a comparison between both approaches is performed. Finally, the results of the measurements are verified through calibrated gauges of several dimensions specially designed for the two barrels. On this basis, an experimental database is developed for further analysis aiming to quantify the relationship between the volume of wear and the muzzle velocity of small caliber guns.

Keywords: coordinate measuring machine, measurement uncertainty, erosion and wear volume, small caliber guns

Procedia PDF Downloads 129

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 158

Authors: Jyh-Ping Chen, Chia-Lin Sheu

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In this study, we propose to use electrospinning to fabricate porous nanofibrous membranes as postsurgical anti-adhesion barriers and to improve the properties of current post-surgical anti-adhesion products. We propose to combine FDA-approved biomaterials with anti-adhesion properties, polycaprolactone (PCL), polyethylene glycol (PEG), hyaluronic acid (HA) with silver nanoparticles (Ag) and ibuprofen (IBU), to produce anti-adhesion barrier nanofibrous membranes. For this purpose, PEG/PCL/Ag/HA/IBU core-shell nanofibers were prepared. The shell layer contains PEG + PCL to provide mechanical supports and Ag was added to the outer PEG-PCL shell layer during electrospinning to endow the nanofibrous membrane with anti-bacterial properties. The core contains HA to exert anti-adhesion and IBU to exert anti-inflammation effects, respectively. The nanofibrous structure of the membranes can reduce cell penetration while allowing nutrient and waste transports to prevent postsurgical adhesion. Nanofibers with different core/shell thickness ratio were prepared. The nanofibrous membranes were first characterized for their physico-chemical properties in detail, followed by in vitro cell culture studies for cell attachment and proliferation. The HA released from the core region showed extended release up to 21 days for prolonged anti-adhesion effects. The attachment of adhesion-forming fibroblasts is reduced using the nanofibrous membrane from DNA assays and confocal microscopic observation of adhesion protein vinculin expression. The Ag released from the shell showed burst release to prevent E Coli and S. aureus infection immediately and prevent bacterial resistance to Ag. Minimum cytotoxicity was observed from Ag and IBU when fibroblasts were culture with the extraction medium of the nanofibrous membranes. The peritendinous anti-adhesion model in rabbits and the peritoneal anti-adhesion model in rats were used to test the efficacy of the anti-adhesion barriers as determined by gross observation, histology, and biomechanical tests. Within all membranes, the PEG/PCL/Ag/HA/IBU core-shell nanofibers showed the best reduction in cell attachment and proliferation when tested with fibroblasts in vitro. The PEG/PCL/Ag/HA/IBU nanofibrous membranes also showed significant improvement in preventing both peritendinous and peritoneal adhesions when compared with other groups and a commercial adhesion barrier film.

Keywords: anti-adhesion, electrospinning, hyaluronic acid, ibuprofen, nanofibers

Procedia PDF Downloads 162

Authors: Gökçe Erdemir, İlhan Yaylım, Serap Erdem-Kuruca, Musa Mutlu Can

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It has been determined that the main reason for the death of cancer disease is caused by metastases rather than the primary tumor. The cells that leave the primary tumor and enter the circulation and cause metastasis in the secondary organs are called "circulating tumor cells" (CTCs). The presence and number of circulating tumor cells has been associated with poor prognosis in many major types of cancer, including breast, prostate, and colorectal cancer. It is thought that knowledge of circulating tumor cells, which are seen as the main cause of cancer-related deaths due to metastasis, plays a key role in the diagnosis and treatment of cancer. The fact that tissue biopsies used in cancer diagnosis and follow-up are an invasive method and are insufficient in understanding the risk of metastasis and the progression of the disease have led to new searches. Liquid biopsy tests performed with a small amount of blood sample taken from the patient for the detection of CTCs are easy and reliable, as well as allowing more than one sample to be taken over time to follow the prognosis. However, since these cells are found in very small amounts in the blood, it is very difficult to capture them and specially designed analytical techniques and devices are required. Methods based on the biological and physical properties of the cells are used to capture these cells in the blood. Early diagnosis is very important in following the prognosis of tumors of epithelial origin such as breast, lung, colon and prostate. Molecules such as EpCAM, vimentin, and cytokeratins are expressed on the surface of cells that pass into the circulation from very few primary tumors and reach secondary organs from the circulation, and are used in the diagnosis of cancer in the early stage. For example, increased EpCAM expression in breast and prostate cancer has been associated with prognosis. These molecules can be determined in some blood or body fluids to be taken from patients. However, more sensitive methods are required to be able to determine when they are at a low level according to the course of the disease. The aim is to detect these molecules found in very few cancer cells with the help of sensitive, fast-sensing biosensors, first in breast cancer cells reproduced in vitro and then in blood samples taken from breast cancer patients. In this way, cancer cells can be diagnosed early and easily and effectively treated.

Keywords: electrochemical biosensors, breast cancer, circulating tumor cells, EpCAM, Vimentin, Cytokeratins

Procedia PDF Downloads 242

Authors: C. Yin, B. Zhang, Y. Liu, J. Cai

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Airborne EM (AEM) is an effective geophysical exploration tool, especially suitable for ridged mountain areas. In these areas, topography will have serious effects on AEM system responses. However, until now little study has been reported on topographic effect on airborne EM systems. In this paper, an edge-based unstructured finite-element (FE) method is developed for 3D topographic modeling for both frequency and time-domain airborne EM systems. Starting from the frequency-domain Maxwell equations, a vector Helmholtz equation is derived to obtain a stable and accurate solution. Considering that the AEM transmitter and receiver are both located in the air, the scattered field method is used in our modeling. The Galerkin method is applied to discretize the Helmholtz equation for the final FE equations. Solving the FE equations, the frequency-domain AEM responses are obtained. To accelerate the calculation speed, the response of source in free-space is used as the primary field and the PARDISO direct solver is used to deal with the problem with multiple transmitting sources. After calculating the frequency-domain AEM responses, a Hankel’s transform is applied to obtain the time-domain AEM responses. To check the accuracy of present algorithm and to analyze the characteristic of topographic effect on airborne EM systems, both the frequency- and time-domain AEM responses for 3 model groups are simulated: 1) a flat half-space model that has a semi-analytical solution of EM response; 2) a valley or hill earth model; 3) a valley or hill earth with an abnormal body embedded. Numerical experiments show that close to the node points of the topography, AEM responses demonstrate sharp changes. Special attentions need to be paid to the topographic effects when interpreting AEM survey data over rugged topographic areas. Besides, the profile of the AEM responses presents a mirror relation with the topographic earth surface. In comparison to the topographic effect that mainly occurs at the high-frequency end and early time channels, the EM responses of underground conductors mainly occur at low frequencies and later time channels. For the signal of the same time channel, the dB/dt field reflects the change of conductivity better than the B-field. The research of this paper will serve airborne EM in the identification and correction of the topographic effects.

Keywords: 3D, Airborne EM, forward modeling, topographic effect

Procedia PDF Downloads 295

Authors: Nicola Menga, Giuseppe Carbone

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Although contact mechanics has been widely focused on the study of contacts between half-space, it has been recently pointed out that in presence of finite thickness elastic layers the results of the contact problem show significant difference in terms of the main contact quantities (e.g. contact area, penetration, mean pressure, etc.). Actually, there exist a wide range of industrial application demanding for this kind of studies, such as seals leakage prediction or pressure-sensitive coatings for electrical applications. In this work, we focus on the contact between a rigid profile and an elastic layer of thickness h confined under two different configurations: rigid constrain and applied uniform pressure. The elastic problem at hand has been formalized following Green’s function method and then numerically solved by means of a matrix inversion. We study different contact conditions, both considering and neglecting adhesive interactions at the interface. This leads to different solution techniques: Adhesive contacts equilibrium solution is found, in term of contact area for given penetration, making stationary the total free energy of the system; whereas, adhesiveless contacts are addressed defining an equilibrium criterion, again on the contact area, relying on the fracture mechanics stress intensity factor KI. In particular, we make the KI vanish at the edges of the contact area, as peculiar for adhesiveless elastic contacts. The results are obtained in terms of contact area, penetration, and mean pressure for both adhesive and adhesiveless contact conditions. As expected, in the case of a uniform applied pressure the slab turns out much more compliant than the rigidly constrained one. Indeed, we have observed that the peak value of the contact pressure, for both the adhesive and adhesiveless condition, is much higher for the rigidly constrained configuration than in the case of applied uniform pressure. Furthermore, we observed that, for little contact area, both systems behave the same and the pull-off occurs at approximately the same contact area and mean contact pressure. This is an expected result since in this condition the ratio between the layers thickness and the contact area is very high and both layer configurations recover the half-space behavior where the pull-off occurrence is mainly controlled by the adhesive interactions, which are kept constant among the cases.

Keywords: contact mechanics, adhesion, friction, thick layer

Procedia PDF Downloads 488

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

Procedia PDF Downloads 380

Authors: Mwafaq Ibdah, Mossab, Yahyaa, Dor Rachmany, Yoram Gerchman, Doron Holland, Liora Shaltiel-Harpaz

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Pear Psylla is the most important pest of pear in all pear-growing regions, in Asian, European, and the USA. Pear psylla damages pears in several ways: high-density populations of these insects can cause premature leaf and fruit drop, diminish plant growth, and reduce fruit size. In addition, their honeydew promotes sooty mold on leaves and russeting on fruit. Pear psyllas are also considered vectors of pear pathogens such as Candidatus Phytoplasma pyri causing pear decline that can lead to loss of crop and tree vigor, and sometimes loss of trees. Psylla control is a major obstacle to efficient integrated pest management. Recently we have identified two naturally resistance pear accessions (Py.760-261 and Py.701-202) in the Newe Ya’ar live collection. GC-MS volatile metabolic profiling identified several volatile compounds common in these accessions but lacking, or much less common, in a sensitive accession, the commercial Spadona variety. Among these volatiles were styrene and its derivatives. When the resistant accessions were used as inter-stock, the volatile compounds appear in commercial Spadona scion leaves, and it showed reduced susceptibility to pear psylla. Laboratory experiments and applications of some of these volatile compounds were very effective against psylla eggs, nymphs, and adults. The genes and enzymes involved in the specific reactions that lead to the biosynthesis of styrene in plant are unknown. We have identified a phenolic acid decarboxylase that catalyzes the formation of p-hydroxystyrene, which occurs as a styrene analog in resistant pear genotypes. The His-tagged and affinity chromatography purified E. coli-expressed pear PyPAD1 protein could decarboxylate p-coumaric acid and ferulic acid to p-hydroxystyrene and 3-methoxy-4-hydroxystyrene. In addition, PyPAD1 had the highest activity toward p-coumaric acid. Expression analysis of the PyPAD gene revealed that its expressed as expected, i.e., high when styrene levels and psylla resistance were high.

Keywords: pear Psylla, volatile, GC-MS, resistance

Procedia PDF Downloads 125

Authors: Kang Liu, Meng Liu, Meng-Long Wu, Da-Chang Yue, Hong-Yi Pan

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The soil setup is an important factor affecting pile bearing capacity; there are many factors that influence it, all of which are closely related to pile construction disturbances. During pile installation in soil, a significant amount of excess pore pressure is generated, creating disturbance zones around the pile. The dissipation rate of excess pore pressure is an important factor influencing the pile setup. The paper aims to examine how alterations in parameters within disturbance zones affect the dissipation of excess pore pressure. An axisymmetric FE model is used to simulate pile installation in clay, subsequently consolidation using Plaxis 3D. The influence of disturbed zone on setup is verified, by comparing the parametric studies in uniform field and non-uniform field. Three types of consolidation are employed: consolidation in three directions, vertical consolidation, horizontal consolidation. The results of the parametric study show that the permeability coefficient decreases, soil stiffness decreases, and reference pressure increases in the disturbance zone, resulting in an increase in the dissipation time of excess pore pressure and exhibiting a noticeable threshold phenomenon, which has been commonly overlooked in previous literature. The research in this paper suggests that significant thresholds occur when the coefficient of permeability decreases to half of the original site's value for three-directional and horizontal consolidation within the disturbed zone. Similarly, the threshold for vertical consolidation is observed when the coefficient of permeability decreases to one-fourth of the original site's value. Especially in pile setup research, consolidation is assumed to be horizontal; the study findings suggest that horizontal consolidation has experienced notable alterations as a result of the presence of disturbed zones. Furthermore, the selection of pile installation methods proves to be critical. A nonlinearity excess pore pressure formula is proposed based on cavity expansion theory, which includes the distribution of soil profile modulus with depth.

Keywords: pile setup, threshold value effect, installation effects, uniform field, non-uniform field

Procedia PDF Downloads 21

Authors: Hager Elsheikh, Juliane Glaubitz, Frank Ulrich Weiss, Matthias Sendler

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Aim: Acute pancreatitis (AP) and chronic pancreatitis (CP) are both accompanied by a prominent immune response which influences the course of disease. Whereas during AP the pro-inflammatory immune response dominates, during CP a fibroinflammatory response regulates organ remodeling. The transcription factor signal transducer and activator of transcription 6 (STAT6) is a crucial part of the Type 2 immune response. Here we investigate the role of STAT6 in a mouse model of AP and CP. Material and Methods: AP was induced by hourly repetitive i.p. injections of caerulein (50µg/kg/bodyweight) in C57Bl/6 J and STAT6-/- mice. CP was induced by repetitive caerulein injections 6 times a day, 3 days a week over 4 weeks. Disease severity was evaluated by serum amylase/lipase measurement, H&E staining of pancreas. Pancreatic infiltrate was characterized by immunofluorescent labeling of CD68, CD206, CCR2, CD4 and CD8. Pancreas fibrosis was evaluated by Azan blue staining. qRT-PCR was performed of Arg1, Nos2, Il6, Il1b, Col3a, Socs3 and Ym1. Affymetrix chip array analyses were done to illustrate the IL4/IL13/STAT6 signaling in bone marrow derived macrophages. Results: AP severity is mitigated in STAT6-/- mice, as shown by decreased serum amylase and lipase, as well as histological damage. CP mice surprisingly showed only slightly reduced fibrosis of the pancreas. Also staining of CD206 a classical marker of alternatively activated macrophages showed no decrease of M2-like polarization in the absence of STAT6. In contrast, transcription profile analysis in BMDM showed complete blockade of the IL4/IL13 pathway in STAT6-/- animals. Conclusion: STAT6 signaling pathway is protective during AP and mitigates the pancreatic damage. During chronic pancreatitis the IL4/IL13 – STAT6 axisis involved in organ fibrogenesis. Notably, fibrosis is not dependent on a single signaling pathway, and alternative macrophage activation is also complex and involves different subclasses (M2a, M2b, M2c and M2d) which could be independent of the IL4/IL13 STAT6 axis.

Keywords: chronic pancreatitis, macrophages, IL4/IL13, Type immune response

Procedia PDF Downloads 41

Authors: Christina Williams, Mehari Weldemariam, Ann M. Farese, Thomas J. MacVittie, Maureen A. Kane

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Radiation exposure results in dose-dependent and time-dependent multi-organ damage. Drug development of medical countermeasures (MCM) for radiation-induced injury occurs under the FDA Animal Rule because human efficacy studies are not ethical or feasible. The FDA Animal Rule requires the representation of both sexes and describes several uses for biomarkers in MCM drug development studies. Currently, MCMs are limited and there is no FDA-approved biomarker for any radiation injury. Sex as a variable is essential to identifying biomarkers and developing effective MCMs for acute radiation exposure (ARS) and delayed effects of acute radiation exposure (DEARE). These studies aim to address the death of information on sex differences that have not been determined by studies that included only male, single-sex cohorts. Studies have reported differences in radiosensitivity according to sex. As such, biomarker discovery for radiation-induced damage must consider sex as a variable. This study evaluated the plasma proteomic profile of Rhesus macaque non-human primates after different exposures and doses, as well as time points after radiation. Exposures and doses included total body irradiation between 5-7.5 Gy and partial body irradiation with 5% bone marrow sparing at 9, 9.5 and 10 Gy. Timepoints after irradiation included days 1, 3, 60, and 180, which encompassed both acute radiation syndromes and delayed effects of acute radiation exposure. Bottom-up proteomic analyses of plasma included equal numbers of males and females. In the control animals, few proteomic differences are observed between the sexes. In the irradiated animals, there are a few sex differences, with changes mostly consisting of proteins upregulated in the female animals. Multiple canonical pathways were upregulated in irradiated animals relative to the control animals when subjected to pathway analysis, but differential responses between the sexes are limited. These data provide critical baseline differences according to sex and establish sex differences in non-human primate models relevant to drug development of MCM under the FDA Animal Rule.

Keywords: ionizing radiation, sex differences, plasma proteomics, biomarker discovery

Procedia PDF Downloads 67

Authors: Nima Samie, Batoul Sadat Haerian, Sekaran Muniandy, M. S. Kanthimathi

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Colon and breast cancers are categorized as the most prevalent types of cancer worldwide. Recently, the broad clinical application of metal complex compounds has led to the discovery of potential therapeutic drugs. The aim of this study was to evaluate the cytotoxic action of a selected nickel complex compound (NCC) against human colon and breast cancer cells. In this context, we determined the potency of the compound in the induction of apoptosis, cell cycle arrest, and cytoskeleton rearrangement. HT-29, WiDr, CCD-18Co, MCF-7 and Hs 190.T cell lines were used to determine the IC50 of the compound using the MTT assay. Analysis of apoptosis was carried out using immunofluorescence, acridine orange/ propidium iodide double staining, Annexin-V-FITC assay, evaluation of the translocation of NF-kB, oxygen radical antioxidant capacity, quenching of reactive oxygen species content , measurement of LDH release, caspase-3/-7, -8 and -9 assays and western blotting. The cell cycle arrest was examined using flowcytometry and gene expression was assessed using qPCR array. Results showed that our nickel complex compound displayed a potent suppressive effect on HT-29, WiDr, MCF-7 and Hs 190.T after 24 h of treatment with IC50 value of 2.02±0.54, 2.13±0.65, 3.76±015 and 3.14±0.45 µM respectively. This cytotoxic effect on normal cells was insignificant. Dipping in the mitochondrial membrane potential and increased release of cytochrome c from the mitochondria indicated induction of the intrinsic apoptosis pathway by the nickel complex compound. Activation of this pathway was further evidenced by significant activation of caspase 9 and 3/7.The nickel complex compound (NCC) was also shown activate the extrinsic pathways of apoptosis by activation of caspase-8 which is linked to the suppression of NF-kB translocation to the nucleus. Cell cycle arrest in the G1 phase and up-regulation of glutathione reductase, based on excessive ROS production were also observed. The results of this study suggest that the nickel complex compound is a potent anti-cancer agent inducing both intrinsic and extrinsic pathways as well as cell cycle arrest in colon and breast cancer cells.

Keywords: nickel complex, apoptosis, cytoskeletal rearrangement, colon cancer, breast cancer

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Authors: Pakinee Pooprasert, Wanxin Wang, Tina Parmar, Dana Ahnood, Tafadzwa Young-Zvandasara, James Morgan

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Homelessness has been shown to be correlated to poor health outcomes, including increased visual health morbidity. Despite this, there are relatively few studies regarding visual health in the homeless population, especially in the UK. This research aims to investigate visual disability and access barriers prevalent in the homeless population in Cardiff, South Wales. Data was collected from 100 homeless participants in three different shelters. Visual outcomes included near and distance visual acuity as well as non-cycloplegic refraction. Qualitative data was collected via a questionnaire and included socio-demographic profile, ocular history, subjective visual acuity and level of access to healthcare facilities. Based on the participants’ presenting visual acuity, the total prevalence of myopia and hyperopia was 17.0% and 19.0% respectively based on spherical equivalent from the eye with the greatest absolute value. The prevalence of astigmatism was 8.0%. The mean absolute spherical equivalent was 0.841D and 0.853D for right and left eye respectively. The number of participants with sight loss (as defined by VA= 6/12-6/60 in the better-seeing eye) was 27.0% in comparison to 0.89% and 1.1% in the general Cardiff and Wales population respectively (p-value is < 0.05). Additionally, 1.0% of the homeless subjects were registered blind (VA less than 3/60), in comparison to 0.17% for the national consensus after age standardization. Most participants had good knowledge regarding access to prescription glasses and eye examination services. Despite this, 85.0% never had their eyes examined by a doctor and 73.0% had their last optometrist appointment in more than 5 years. These findings suggested that there was a significant disparity in ocular health, including visual acuity and refractive error amongst the homeless in comparison to the general population. Further, the homeless were less likely to receive the same level of support and continued care in the community due to access barriers. These included a number of socio-economic factors such as travel expenses and regional availability of services, as well as administrative shortcomings. In conclusion, this research demonstrated unmet visual health needs within the homeless, and that inclusive policy changes may need to be implemented for better healthcare outcomes within this marginalized community.

Keywords: homelessness, refractive error, visual disability, Wales

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Authors: Ellen Dahl Gundersen, Berit Johannessen

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Introduction: Dementia and depression are common mental disorders of nursing home residents. The care of these residents consists of providing both physical, social and mental care. Too often, the physical needs are given priority, and municipal health services are urged to focus more on the patients mental and social needs. The presence of dogs may have positive impact on the mental health of nursing home residents by improving mood, social interaction and enjoyment of the visits. The voluntary organization Red Cross, has given priority to this subject by training and certifying dogs and owners (equipages), committed for regular visits at local nursing homes. Focus of this study: How do the dog owners and employees experience the presence of a dog equipage concerning the mental health of nursing home residents? Method: Individual interviews with 8-10 certified dog owners who are volunteers from Red Cross, contributing with regular visits at local nursing homes. Focus group interviews with 10 employees working in two different nursing homes. Preliminary results: Five to seven residents and one or two employees attended weekly dog equipage visits during a period of six months. The presence of an equipage seems to have made the residents calm and more social orientated with a lighter mood and better verbal expression. Some of the residents with dementia remembered the name of the dog from one week to another. The informants also reported positive outcome for the residents by their opportunity to give and get close through physical contact with a dog. Further, the presence of an equipage affected the atmosphere at the nursing home positively by promoting joy and initiating conversations about dogs. A conscious approach by the dog owners towards the residents seems to be of significance to this matter. The positive attitude and support from employees also seem to be of crucial importance for the maintenance of these visits. Conclusion: The presence of trained dog equipages in nursing homes seems to have had an overall positive impact on the mental health of residents. A conscious approach from the dog owners as well as positive support from employees seems to have a crucial impact on the success and maintenance of the visits. These findings correspond well to former research and can thereby give implications for more extended use of dogs as a mental health promoting initiative towards geriatric consumers of municipal health care services. Further research through larger studies is needed.

Keywords: animal assisted intervention, geriatric mental health, nursing home, resident

Procedia PDF Downloads 245

Authors: Florenda B. Cardinoza

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This study was conducted to determine the determinants of Grade III and grade VI pupils’ performance in the National Achievement Test in the Division of Cavite City, School Year 2011-2012. Specifically, the research aimed to: (1) describe the demographic profile of the respondents in terms of age, sex, birth order, family size, family income, and occupation of parents; (2) determine the level of attitude towards NAT; and (3) describe the degree of relationship between the following variables: school support, teachers’ support, and lastly family support for the pupils’ performance in 2012 NAT. The study used the descriptive-correlation research method to investigate the determinants of pupils’ performance in the National Achievement Test of Public Elementary Schools in the Division of Cavite City. The instrument used in data gathering was a self-structured survey. The NAT result for SY 2011-2012 provided by NETRC and DepEd Cavite City was also utilized. The statistical tools used to process and analyze the data were frequency distribution, percentage, mean, standard deviation, Kruskall Wallis, Mann-Whitney, t-test for independent samples, One-way ANOVA, and Spearman Rank Correlational Coefficient. Results revealed that there were more female students than males in the Division of Cavite City; out of 659 respondents, 345 were 11 years old and above; 390 were females; 283 were categorized as first child in the family; 371 of the respondents were from small family; 327 had Php5000 and below family income; 450 of the fathers’ respondents were non professionals; and 431 of the mothers respondents had no occupation. The attitude towards NAT, with a mean of 1.65 and SD of .485, shows that respondents considered NAT important. The school support towards NAT, with a mean of 1.89 and SD of .520, shows that respondents received school support. The pupils had a very high attitude towards teachers’ support in NAT with a mean of 1.60 and SD of .572. Family support, with t-test of 16.201 with a p-value of 0.006, shows significant at 5 percent level. Thus, the determinants of pupils’ performance in NAT in terms of family support for NAT preparation is not significant according to their family income. The grade level, with the t-test is 4.420 and a p-value of 0.000, is significant at 5 percent level. Therefore, the determinants of pupils’ performance in NAT in terms of grade level for NAT preparation vary according to their grade level. For the determinants of pupils’ performance of NAT sample test for attitude towards NAT, school support, teachers’ support, and family support were noted highly significant with a p value of 0.000.

Keywords: achievement, determinants, national, performance, public, pupils', test

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Authors: Abdul Qadir Jangda, Khadija Mariam, Usman Ahmed, Sharib Ahmed

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The Gafchromic EBT3 film has the characteristic of high spatial resolution, weak energy dependence and near tissue equivalence which makes them viable to be used for in-vivo dosimetry in External Beam and Brachytherapy applications. The aim of this study is to assess the smallest film dimension that may be feasible for the use in in-vivo dosimetry. To evaluate the viability, the film sizes from 3 x 3 mm to 20 x 20 mm were calibrated with 6 MV Photon and 6 MeV electron beams. The Gafchromic EBT3 (Lot no. A05151201, Make: ISP) film was cut into five different sizes in order to establish the relationship between absorbed dose vs. film dimensions. The film dimension were 3 x 3, 5 x 5, 10 x 10, 15 x 15, and 20 x 20 mm. The films were irradiated on Varian Clinac® 2100C linear accelerator for dose range from 0 to 1000 cGy using PTW solid water phantom. The irradiation was performed as per clinical absolute dose rate calibratin setup, i.e. 100 cm SAD, 5.0 cm depth and field size of 10x10 cm2 and 100 cm SSD, 1.4 cm depth and 15x15 cm2 applicator for photon and electron respectively. The irradiated films were scanned with the landscape orientation and a post development time of 48 hours (minimum). Film scanning accomplished using Epson Expression 10000 XL Flatbed Scanner and quantitative analysis carried out with ImageJ freeware software. Results show that the dose variation with different film dimension ranging from 3 x 3 mm to 20 x 20 mm is very minimal with a maximum standard deviation of 0.0058 in Optical Density for a dose level of 3000 cGy and the the standard deviation increases with the increase in dose level. So the precaution must be taken while using the small dimension films for higher doses. Analysis shows that there is insignificant variation in the absorbed dose with a change in film dimension of EBT3 film. Study concludes that the film dimension upto 3 x 3 mm can safely be used up to a dose level of 3000 cGy without the need of recalibration for particular dimension in use for dosimetric application. However, for higher dose levels, one may need to calibrate the films for a particular dimension in use for higher accuracy. It was also noticed that the crystalline structure of the film got damage at the edges while cutting the film, which can contribute to the wrong dose if the region of interest includes the damage area of the film

Keywords: external beam radiotherapy, film calibration, film dosimetery, in-vivo dosimetery

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Authors: Nor Azlina A. Rahman, Jamaliah Said, Salwana Hassan

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Prompt changes in global business environment, such as passionate competition, managerial/operational, changing governmental regulation and innovation in technology have significant impacts on the organizations. At present, global business environment demands for more proactive institutions on microfinance to provide an opportunity for the business success. Microfinance providers in Malaysia still accelerate its activities of funding by cash and cheque. These institutions are at high risk as the paper-based system is deemed to be slow and prone to human error, as well as requiring a major annual reconciliation process. The global transformation of financial services, growing involvement of technology, innovation and new business activities had progressively made risk management profile to be more subjective and diversified. The persistent, complex and dynamic nature of risk management activities in the institutions arise due to highly automated advancements of technology. This may thus manifest in a variety of ways throughout the financial services sector. This study seeks out to examine current operational risks management being experienced by microfinance providers in Malaysia; investigate the process of current practices on facilitator control factor mechanisms, and explore how the adoption of technology, innovation and use of management accounting practices would affect the risk management process of operation system in microfinance providers in Malaysia. A case study method was employed in this study. The case study also need to find that the vital past role of management accounting will be used for mitigation of risk management activities towards accountability as an information or guideline to microfinance provider. An empirical element obtainable with qualitative method is needed in this study, where multipart and in-depth information are essential to understand the issues of these institution phenomena. This study is expected to propose a theoretical model for implementation of technology, innovation and management accounting practices into the system of operation to improve internal control and subsequently lead to mitigation of risk management activities among microfinance providers to be more successful.

Keywords: microfinance, accountability, operational risks, management accounting practices

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Authors: Mia Françoise

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This report aims to develop a strategy for assisting short-term investors to benefit from the current economic climate in South Africa by utilizing technical analysis techniques and predictive analytics. As part of this research, value investing and technical analysis principles will be combined to maximize returns for South African investors while optimizing volatility. As an emerging market, South Africa offers many opportunities for high growth in sectors where other developed countries cannot grow at the same rate. Investing in South African companies with significant growth potential can be extremely rewarding. Although the risk involved is more significant in countries with less developed markets and infrastructure, there is more room for growth in these countries. According to recent research, the offshore market is expected to outperform the local market over the long term; however, short-term investments in the local market will likely be more profitable, as the Johannesburg Stock Exchange is predicted to outperform the S&P500 over the short term. The instabilities in the economy contribute to increased market volatility, which can benefit investors if appropriately utilized. Price prediction and portfolio optimization comprise the two primary components of this methodology. As part of this process, statistics and other predictive modeling techniques will be used to predict the future performance of stocks listed on the Johannesburg Stock Exchange. Following predictive data analysis, Modern Portfolio Theory, based on Markowitz's Mean-Variance Theorem, will be applied to optimize the allocation of assets within an investment portfolio. By combining different assets within an investment portfolio, this optimization method produces a portfolio with an optimal ratio of expected risk to expected return. This methodology aims to provide a short-term investment with a stock portfolio that offers the best risk-to-return profile for stocks listed on the JSE by combining price prediction and portfolio optimization.

Keywords: financial stocks, optimized asset allocation, prediction modelling, South Africa

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Authors: David Serero, Loic Couton, Jean-Denis Parisse, Robert Leroy

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This paper presents an analysis method of airflow at the periphery of several typologies of architectural volumes. To understand the complexity of the urban environment on the airflows in the city, we compared three sites at different architectural scale. The research sets a method to identify the optimal location for the installation of wind turbines on the edges of a building and to achieve an improvement in the performance of energy extracted by precise localization of an accelerating wing called “aero foil”. The objective is to define principles for the installation of wind turbines and natural ventilation design of buildings. Instead of theoretical winds analysis, we combined numerical aeraulic simulations using STAR CCM + software with wind data, over long periods of time (greater than 1 year). If airflows computer fluid analysis (CFD) simulation of buildings are current, we have calibrated a virtual wind tunnel with wind data using in situ anemometers (to establish localized cartography of urban winds). We can then develop a complete volumetric model of the behavior of the wind on a roof area, or an entire urban island. With this method, we can categorize: - the different types of wind in urban areas and identify the minimum and maximum wind spectrum, - select the type of harvesting devices - fixing to the roof of a building, - the altimetry of the device in relation to the levels of the roofs - The potential nuisances around. This study is carried out from the recovery of a geolocated data flow, and the connection of this information with the technical specifications of wind turbines, their energy performance and their speed of engagement. Thanks to this method, we can thus define the characteristics of wind turbines to maximize their performance in urban sites and in a turbulent airflow regime. We also study the installation of a wind accelerator associated with buildings. The “aerofoils which are integrated are improvement to control the speed of the air, to orientate it on the wind turbine, to accelerate it and to hide, thanks to its profile, the device on the roof of the building.

Keywords: wind energy harvesting, wind turbine selection, urban wind potential analysis, CFD simulation for architectural design

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Authors: Dugeree Otgongerel, Kyong Jin Cho, Yu-Han Kim, Sangmee Ahn Jo

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Excessive activation of glutamate receptor is thought to be involved in retinal ganglion cell (RGC) death after ischemia- reperfusion damage. Glutamate carboxypeptidase II (GCPII) is an enzyme responsible for the synthesis of glutamate. Several studies showed that inhibition of GCPII prevents or reduces cellular damage in brain diseases. Thus, in this study, we examined the expression of GCPII in rat retina and the role of GCPII in acute high IOP ischemia-reperfusion damage of eye by using a GCPII inhibitor, 2-(phosphonomethyl) pentanedioic acid (2-PMPA). Animal model of ischemia-reperfusion was induced by raising the intraocular pressure for 60 min and followed by reperfusion for 3 days. Rats were randomly divided into four groups: either intra-vitreous injection of 2-PMPA (11 or 110 ng per eye) or PBS after ischemia-reperfusion, 2-PMPA treatment without ischemia-reperfusion and sham-operated normal control. GCPII immunoreactivity in normal rat retina was detected weakly in retinal nerve fiber layer (RNFL) and retinal ganglionic cell layer (RGL) and also inner plexiform layer (IPL) and outer plexiform layer (OPL) strongly where are co-stained with an anti-GFAP antibody, suggesting that GCPII is expressed mostly in Muller and astrocytes. Immunostaining with anti-BRN antibody showed that ischemia- reperfusion caused RGC death (31.5 %) and decreased retinal thickness in all layers of damaged retina, but the treatment of 2-PMPA twice at 0 and 48 hour after reperfusion blocked these retinal damages. GCPII level in RNFL layer was enhanced after ischemia-reperfusion but was blocked by PMPA treatment. This result was confirmed by western blot analysis showing that the level of GCPII protein after ischemia- reperfusion increased by 2.2- fold compared to control, but this increase was blocked almost completely by 110 ng PMPA treatment. Interestingly, GFAP immunoreactivity in the retina after ischemia- reperfusion followed by treatment with PMPA showed similar pattern to GCPII, increase after ischemia-reperfusion but reduction to the normal level by PMPA treatment. Our data demonstrate that increase of GCPII protein level after ischemia-reperfusion injury is likely to cause glial activation and/or retinal cell death which are mediated by glutamate, and GCPII inhibitors may be useful in treatment of retinal disorders in which glutamate excitotoxicity is pathogenic.

Keywords: glutamate carboxypepptidase II, glutamate excitotoxicity, ischemia-reperfusion, retinal ganglion cell

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Authors: Vered Holzmann, Ramzi Halabi

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The current research investigates motivators and barriers to high-tech entrepreneurship in the Israeli-Arab Community. With the aim to exploit the capacity of Israel as a 'start-up nation', we identify the most important aspects to promote integration of Israeli-Arab entrepreneurs in high-tech startups and business companies, thus impact the socio-economic status of the Arab community in Israel. We reviewed the literature on the role of high-tech and entrepreneurship in the Israeli economy, the profile of the Israeli-Arab community with regard to education and employability, and the characteristics of minority entrepreneurship to understand entrepreneurs' intentions, their incentives to choose the entrepreneurial route on one hand and the obstacles that they face on the other hand. Based on the literature review, we conducted an integrated study that included a survey among 73 Israeli-Arabs involved in high-tech entrepreneurship and 16 semi-structured interviews with Israeli-Arab and Jewish entrepreneurs and leaders in the high-tech industry. We analyzed the data to explore personal and social motivating factors to entrepreneurship as well as educational and socio-economical barriers for entrepreneurship. Three major elements were found to be the most influential on Arab high-tech entrepreneurship in Israel: education, financial resources, and strategic-institutional support. The relationship between education and employability that is well-known with regard to general education, requires two additional aspects in the field of high-tech entrepreneurship: education of technology and engineering, and education of business and entrepreneurship. The study findings reveal that the main motivation factors for entrepreneurship are development of creative ideas and improvement of the socio-economic status, while financial-related factors and lack of institutional and governmental support are perceived as impediments to entrepreneurial activities. Financing difficulties are mainly derived from discriminating financial environment and lack of professional networking. The relationship between entrepreneurship and economic growth seems to be clear and simple; thus it is a national interest to encourage entrepreneurship among the Arab community, and especially high-tech entrepreneurship which has a significant role in the economic growth of Israel.

Keywords: high-tech industry, innovation management, Israeli-Arab community, minority entrepreneurship, motivating factors and barriers

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Authors: Lukas J. Evans, Danilo D. Fernando

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Shrub willows (Salix spp.) have many characteristics which make them suitable for a variety of applications such as riparian zone buffers, environmental contaminant sequestration, living snow fences, and biofuel production. In some cases, these functions are limited due to physical or financial obstacles associated with the number of individuals needed to reasonably satisfy that purpose. One way to increase the efficiency of willows is to bioengineer them with the genetic improvements suitable for the desired use. To accomplish this goal, an optimized in vitro transformation protocol via Agrobacterium tumefaciens is necessary to reliably express genes of interest. Therefore, the aim of this study is to observe the influence of tissue culture with different willow cultivars, hormones, and explants on the percentage of calli expressing reporter gene green florescent protein (GFP) to find ideal transformation conditions. Each callus was produced from 1 month old open-pollinated seedlings of three Salix miyabeana cultivars (‘SX61’, ‘WT1’, and ‘WT2’) from three different explants (lamina, petiole, and internodes). Explants were cultured for 1 month on an MS media with different concentrations of 6-Benzylaminopurine (BAP) and 1-Naphthaleneacetic acid (NAA) (No hormones, 1 mg⁻¹L BAP only, 3 mg⁻¹L NAA only, 1 mg⁻¹L BAP and 3 mg⁻¹L NAA, and 3 mg⁻¹L BAP and 1 mg⁻¹L NAA) to produce a callus. Samples were then treated with Agrobacterium tumefaciens at an OD600 of 0.6-0.8 to insert the transgene GFP for 30 minutes, co-cultivated for 72 hours, and selected on the same media type they were cultured on with added 7.5 mg⁻¹L of Hygromycin for 1 week before GFP visualization under a UV dissecting scope. Percentage of GFP expressing calli as well as the average number of fluorescing GFP units per callus were recorded and results were evaluated through an ANOVA test (α = 0.05). The WT1 internode-derived calli on media with 3 mg-1L NAA+1 mg⁻¹L BAP and mg⁻¹L BAP alone produced a significantly higher percentage of GFP expressing calli than each other group (19.1% and 19.4%, respectively). Additionally, The WT1 internode group cultured with 3 mg⁻¹L NAA+1 mg⁻¹L BAP produced an average of 2.89 GFP units per callus while the group cultivated with 1 mg⁻¹L BAP produced an average of 0.84 GFP units per callus. In conclusion, genotype, explant choice, and hormones all play a significant role in increasing successful transformation in willows. Future studies to produce whole callus GFP expression and subsequent plantlet regeneration are necessary for a complete willow transformation protocol.

Keywords: agrobacterium, callus, Salix, tissue culture

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Authors: Sajewicz-Krukowska Joanna, Domańska-Blicharz Katarzyna, Tarasiuk Karolina, Marzec-Kotarska Barbara

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Astroviral infections pose a significant problem in the poultry industry, leading to multiple adverse effects such as decreased egg production, breeding disorders, poor weight gain, and even increased mortality. Commonly observed chicken astrovirus (CAstV) was recently reported to be responsible for "white chicks syndrome" associated with increased embryo/chick mortality. The CAstV-mediated pathogenesis in chicken occurs due to complex interactions between the infectious pathogen and the immune system. Many aspects of CAstV-chicken interactions remain unclear, and there is no information available regarding gene expression changes in the chicken's spleen in response to CAstV infection. We aimed to investigate the molecular background triggered by CAstV infection. Ten 21-day-old SPF White Leghorn chickens were divided into two groups of 5 birds each. One group was inoculated with CAstV, and the other was used as the negative control. On 4th dpi, spleen samples were collected and immediately frozen at -70°C for RNA isolation. We analysed transcriptional profiles of the chickens' spleens at the 4th day following infection using RNA-seq to establish differentially expressed genes (DEGs). The RNA-seq findings were verified by quantitative real-time PCR (qRT-PCR). A total of 31959 transcripts were identified in response to CAstV infection. Eventually 45 DEGs (p-value<0.05; Log2Foldchange>1)were recognized in the spleen after CAstV infection (26 upregulated DEGs and 19 downregulated DEGs). qRT-PCR performed on 4 genes (IFIT5, OASL, RASD1, DDX60) confirmed RNAseq results. Top differentially expressed genes belonged to novel putative IFN-induced CAstV restriction factors. Most of the DEGs were associated with RIG-I–like signalling pathway or, more generally, with an innate antiviral response(upregulated: BLEC3, CMPK2, IFIT5, OASL, DDX60, IFI6, and downregulated: SPIK5, SELENOP, HSPA2, TMEM158, RASD1, YWHAB). The study provided a global analysis of host transcriptional changes that occur during CAstV infection in vivo and proved the cell cycle in the spleen and immune signalling in chickens were predominantly affected upon CAstV infection.

Keywords: chicken astrovirus, CastV, RNA-seq, transcriptome, spleen

Procedia PDF Downloads 128

Authors: Tamar Khardziani, Violeta Berikashvili, Mariam Rusitashvili, Eva Kachlishvili, Vladimir Elisashvili, Mikheil Asatiani

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Last years, the search for natural sources of novel and effective antifungal substances became a scientific and technological challenge. In the present research, thirty basidiomycetes isolated from various ecological niches of Georgia and belonging to different taxonomic groups were screened for their antifungal activities against pathogenic fungi such as Aspergillus, Fusarium, and Guignardia bidwellii. Among mushroom tested, several potential producers of antifungal substances have been revealed, such as Schizophyllum commune, Lentinula edodes, Ganoderma abietinum, Fomes fomentarius, Hericium erinaceus, and Trametes versicolor. For mushroom cultivation and expression of antifungal potential, submerged and solid-state fermentations of different plant raw materials were performed and various approaches and strategies have been exploited. Sch. commune appeared as a most promising producer of antifungal compounds. It was established that among different agro-industrial wastes, the presence of mandarin juice production waste in a nutrient medium, causing the significant increase of antifungal activity Sch. commune (growth inhibition: Aspergillus – 59 %, Fusarium – 55 %, G. bidwellii – 78 %, after 3, 2 and 4 days of cultivation, respectively). Besides this, Sch. commune demonstrate similar antifungal activities in the presence of glucose, glycerol, maltose, mannitol, and xylose, and growth inhibition of Fusarium ranged in 41 % - 49 % during 6 days of cultivation. Inhibition of Aspergillus growth inhibition varied in 27 % - 36 %, and inhibition of G. bidwellii was in the range 49 % - 61 %, respectively. Sch. commune under solid-state fermentation of mandarin peels at 13 days of cultivation demonstrates powerful growth inhibition of pathogenic fungi (growth inhibition: Aspergillus – 50 %, Fusarium – 61 %, G. bidwellii – 68 %, after 3, 4, and 4 days of cultivation, respectively) as well as at 20 days old mushroom (growth inhibition: Aspergillus – 41 %, Fusarium – 54 %, G. bidwellii – 66 %, after 3 days of cultivation). It was established that Sch. commune was effective as a producer of antifungal compounds in submerged as well as in solid-state fermentation. Finally, performed study confirms that the higher basidiomycetes possess antifungal potential, which strongly depends on the physiological factors of growth. Acknowledgments: The work was implemented with the financial support of fundamental science project FR-19-3719 by the Shota Rustaveli National Science Foundation of Georgia.

Keywords: antifungal potential, higher basidiomycetes, pathogenic fungi, submerged and solid-state fermentation

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Authors: Mengfei Peng, Serajus Salaheen, Debabrata Biswas

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Lactobacillus casei found in the human intestine and mouth is commonly applied for dairy production. Recently, it was found that some byproducts produced by Lactobacillus exhibited antimicrobial activities against multiple bacteria. Meanwhile, introduction of prebiotic-like foods (e.g. cocoa) or probiotics or both of them as food supplements in human diets as well as in farm animal feeds is believed to be an effective ways in control/reduce the colonization of foodborne bacterial pathogens infection in the gut environment. We hypothesized that cocoa may stimulate the production antimicrobial components of Lactobacillus casei and may potentially inhibit/reduce the colonization and infection of foodborne bacterial pathogens in the gut. Mixed culture of L. casei (LC) with enterohemorrhagic E. coli EDL933 (EHEC), Salmonella Typhimurium LT2 (ST), or Listeria monocytogenes LM2 (LM) showed that LC could competitively exclude (100%) them within 72 h. Further, investigation of cell-free culture supernatant (CFCS) revealed that the antimicrobial effects of LC came from CFCS. CFCS of LC eliminated (100%) EHEC, ST, and LM within 72 h, and 2 h CFCS treatment increased the hydrophobicity of EHEC (5.10 folds), ST (8.48 folds), and LM (2.03 folds). In addition, LC cells exhibited more inhibitive effects than CFCS on cell adhesive and invasive activities of EHEC (52.14% & 90.45%), ST (66.89% & 93.83%), and LM (61.10% & 83.40%). Two clusters of poly-peptides in CFCS were identified by SDS-PAGE, the molecular weights of which are ≈5 KD and 40-45 KD. LC CFCS with overnight growth in the presence of 3% strengthened all of the antimicrobial activities (growth inhibition, outer membrane disruption, and cell infective ability reduction). Liquid chromatography/Mass spectrometry analysis detected 5 unique components in class of flavonoids in LC CFCS with overnight 3% cocoa supplement. Furthermore, qPCR results showed that CFCSs up-regulated the expression level of genes responsible for flagellin synthesis and motility, but down-regulated genes for specific binding and invasion-associated proteins synthesis. The stimulatory effects of cocoa in producing bioactive components of probiotics may aid prevention of foodborne illness caused by major foodborne enteric bacterial pathogens.

Keywords: foodborne pathogens, probiotics, prebiotics, pathogen exclusion

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Authors: Farida Azzouz-Olden, Arthur G. Hunt, Gloria Degrandi-Hoffman

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Bees are confronting several environmental challenges, including the intermingled effects of malnutrition and disease. Intuitively, pollen is the healthiest nutritional choice; however, commercial substitutes, such as BeePro and MegaBee, are widely used. Herein we examined how feeding natural and artificial diets shapes transcription in the abdomen of the honey bee, and how transcription shifts in combination with Nosema parasitism. Gene ontology enrichment revealed that, compared with poor diet (carbohydrates (C)), bees fed pollen (P > C), BeePro (B > C), and MegaBee (M > C) showed a broad upregulation of metabolic processes, especially lipids; however, pollen feeding promoted more functions and superior proteolysis. The superiority of the pollen diet was also evident through the remarkable overexpression of vitellogenin in bees fed pollen instead of MegaBee or BeePro. Upregulation of bioprocesses under carbohydrates feeding compared to pollen (C > P) provided a clear poor nutritional status, uncovering stark expression changes that were slight or absent relatively to BeePro (C > B) or MegaBee (C > M). Poor diet feeding (C > P) induced starvation response genes and hippo signaling pathway, while it repressed growth through different mechanisms. Carbohydrate feeding (C > P) also elicited ‘adult behavior’, and developmental processes suggesting transition to foraging. Finally, it altered the ‘circadian rhythm’, reflecting the role of this mechanism in the adaptation to nutritional stress in mammals. Nosema-infected bees fed pollen compared to carbohydrates (PN > CN) upheld certain bioprocesses of uninfected bees (P > C). Poor nutritional status was more apparent against pollen (CN > PN) than BeePro (CN > BN) or MegaBee (CN > MN). Nosema accentuated the effects of malnutrition since more starvation-response genes and stress response mechanisms were upregulated in CN > PN compared to C > P. The bioprocess ‘Macromolecular complex assembly’ was also enriched in CN > PN, and involved genes associated with human HIV and/or influenza, thus providing potential candidates for bee-Nosema interactions. Finally, the enzyme Duox emerged as essential for guts defense in bees, similarly to Drosophila. These results provide evidence of the superior nutritional status of bees fed pollen instead of artificial substitutes in terms of overall health, even in the presence of a pathogen.

Keywords: honeybee, immunity, Nosema, nutrition, RNA-seq

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Authors: Anuschka Curran, Sandra Barnard

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Coral reefs are of the most diverse and productive ecosystems on the planet, but due to the impact of climate change, these infrastructures are dying off primarily through coral bleaching. Coral bleaching can be described as the process by which zooxanthellae (algal endosymbionts) are expelled from the gastrodermal cavity of the respective coral host, causing increased coral whitening. The general consensus is that mass coral bleaching is due to the dysfunction of photosynthetic processes in the zooxanthellae as a result of the combined action of elevated temperature and light-stress. The question then is, do zooxanthellae have the potential to play a key role in the future of coral reef restoration through genetic engineering? The aim of this study is firstly to review the different zooxanthellae taxa and their traits with respect to environmental stress, and secondly, to review the information available on the protective mechanisms present in zooxanthellae cells when experiencing temperature fluctuations, specifically concentrating on heat shock proteins and the antioxidant stress response of zooxanthellae. The eight clades (A-H) previously recognized were redefined into seven genera. Different zooxanthellae taxa exhibit different traits, such as their photosynthetic stress responses to light and temperature. Zooxanthellae have the ability to determine the amount and type of heat shock proteins (hsps) present during a heat response. The zooxanthellae can regulate both the host’s respective hsps as well as their own. Hsps, generally found in genotype C3 zooxanthellae, such as Hsp70 and Hsp90, contribute to the thermal stress response of the respective coral host. Antioxidant activity found both within exposed coral tissue, and the zooxanthellae cells can prevent coral hosts from expelling their endosymbionts. The up-regulation of gene expression, which may mitigate thermal stress induction of any of the physiological aspects discussed, can ensure stable coral-zooxanthellae symbiosis in the future. It presents a viable alternative strategy to preserve reefs amidst climate change. In conclusion, despite their unusual molecular design, genetic engineering poses as a useful tool in understanding and manipulating variables and systems within zooxanthellae and therefore presents a solution that can ensure stable coral-zooxanthellae symbiosis in the future.

Keywords: antioxidant enzymes, genetic engineering, heat-shock proteins, Symbiodinium

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Authors: Iman Farasat, Howard M. Salis

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The CRISPR/Cas9 system has revolutionized genome engineering by enabling site-directed and high-throughput genome editing, genome insertion, and gene knockdowns in several species, including bacteria, yeast, flies, worms, and human cell lines. This technology has the potential to enable human gene therapy to treat genetic diseases and cancer at the molecular level; however, the current CRISPR/Cas9 system suffers from seemingly sporadic off-target genome mutagenesis that prevents its use in gene therapy. A comprehensive mechanistic model that explains how the CRISPR/Cas9 functions would enable the rational design of the guide-RNAs responsible for target site selection while minimizing unexpected genome mutagenesis. Here, we present the first quantitative model of the CRISPR/Cas9 genome mutagenesis system that predicts how guide-RNA sequences (crRNAs) control target site selection and cleavage activity. We used statistical thermodynamics and law of mass action to develop a five-step biophysical model of cas9 cleavage, and examined it in vivo and in vitro. To predict a crRNA's binding specificities and cleavage rates, we then compiled a nearest neighbor (NN) energy model that accounts for all possible base pairings and mismatches between the crRNA and the possible genomic DNA sites. These calculations correctly predicted crRNA specificity across 5518 sites. Our analysis reveals that cas9 activity and specificity are anti-correlated, and, the trade-off between them is the determining factor in performing an RNA-mediated cleavage with minimal off-targets. To find an optimal solution, we first created a scheme of safe-design criteria for Cas9 target selection by systematic analysis of available high throughput measurements. We then used our biophysical model to determine the optimal Cas9 expression levels and timing that maximizes on-target cleavage and minimizes off-target activity. We successfully applied this approach in bacterial and mammalian cell lines to reduce off-target activity to near background mutagenesis level while maintaining high on-target cleavage rate.

Keywords: biophysical model, CRISPR, Cas9, genome editing

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Authors: Yuanrui Xu, Zailin Yang, Yunqiu Song, Guanxixi Jiang

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It is an important subject of seismology on the influence of local topography on ground motion during earthquake. In mountainous areas with complex terrain, the construction of the tunnel is often the most effective transportation scheme. In these projects, the local terrain can be simplified into hills with different shapes, and the underground tunnel structure can be regarded as a subsurface cavity. The presence of the subsurface cavity affects the strength of the rock mass and changes the deformation and failure characteristics. Moreover, the scattering of the elastic waves by underground structures usually interacts with local terrains, which leads to a significant influence on the surface displacement of the terrains. Therefore, it is of great practical significance to study the surface displacement of local terrains with underground tunnels in earthquake engineering and seismology. In this work, the region is divided into three regions by the method of region matching. By using the fractional Bessel function and Hankel function, the complex function method, and the wave function expansion method, the wavefield expression of SH waves is introduced. With the help of a constitutive relation between the displacement and the stress components, the hoop stress and radial stress is obtained subsequently. Then, utilizing the continuous condition at different region boundaries, the undetermined coefficients in wave fields are solved by the Fourier series expansion and truncation of the finite term. Finally, the validity of the method is verified, and the surface displacement amplitude is calculated. The surface displacement amplitude curve is discussed in the numerical results. The results show that different parameters, such as radius and buried depth of the tunnel, wave number, and incident angle of the SH wave, have a significant influence on the amplitude of surface displacement. For the underground tunnel, the increase of buried depth will make the response of surface displacement amplitude increases at first and then decreases. However, the increase of radius leads the response of surface displacement amplitude to appear an opposite phenomenon. The increase of SH wave number can enlarge the amplitude of surface displacement, and the change of incident angle can obviously affect the amplitude fluctuation.

Keywords: method of region matching, scattering of SH wave, subsurface cavity, trapezoidal hill

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