Search results for: human cells line

Authors: Khairy M. A. Zoheir

Abstract:

One of the most severe complications of Rheumatoid arthritis is delayed recovery. lipoic acid possesses antioxidant, hypoglycemic, and anti-inflammatory activity. In the present study, the effects of lipoic acid was investigated on the key mediators of Rheumatoid arthritis, namely, CD4+CD25+ T cell subsets, GITR expressing cells, CD4+CD25+Foxp3+ regulatory T (Treg) cells, T-helper-17 (Th17) cells, and pro-inflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor- α (TNF-α)] through flow-cytometry and qPCR analyses. Lipoic acid treated mice showed a significant decrease in the Rheumatoid arthritis, the frequency of GITR-expressing cells, and Th1 cytokines (IL-17A, TNF-αand Interferon- γ (IFN-γ) compared with positive and negative controlled mice. Lipoic acid treatment also down regulated the mRNA expression of the inflammatory mediators compared with the Rheumatoid arthritis mouse model and untreated mice. The number of Tregs also found to be significantly upregulated in lipoic acid treated mice. Our results were confirmed by the histopathological examination. This study showed the beneficial role of lipoic acid in promoting a well-balanced tool for therapy Rheumatoid arthritis.

Keywords: lipoic acid, chemokines, inflammatory, rheumatoid arthritis

Procedia PDF Downloads 158

Authors: Salina Yahya Saddick

Abstract:

Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

Procedia PDF Downloads 359

Authors: M. Maleczek, Leszek Bogdan, Kazimierz Drabczyk, Agnieszka Iwan

Abstract:

Crystalline silicon (Si) solar cells are the main product in the market among the various photovoltaic technologies concerning such advantages as: material richness, high carrier mobilities, broad spectral absorption range and established technology. However, photovoltaic technology on the stiff substrates are heavier, more fragile and less cost-effective than devices on the flexible substrates to be applied in special applications. The main goal of our work was to incorporate silicon solar cells into various fabric, without any change of the electrical and mechanical parameters of devices. This work is realized for the GEKON project (No. GEKON2/O4/268473/23/2016) sponsored by The National Centre for Research and Development and The National Fund for Environmental Protection and Water Management. In our work, the polyamide or polyester fabrics were used as a flexible substrate in the created devices. Applied fabrics differ in tensile and tear strength. All investigated polyamide fabrics are resistant to weathering and UV, while polyester ones is resistant to ozone, water and ageing. The examined fabrics are tight at 100 cm water per 2 hours. In our work, commercial silicon solar cells with the size 156 × 156 mm were cut into nine parts (called single solar cells) by diamond saw and laser. Gap and edge after cutting of solar cells were checked by transmission electron microscope (TEM) to study morphology and quality of the prepared single solar cells. Modules with the size of 160 × 70 cm (containing about 80 single solar cells) were created and investigated by electrical and mechanical methods. Weight of constructed module is about 1.9 kg. Three types of solar cell architectures such as: -fabric/EVA/Si solar cell/EVA/film for lamination, -backsheet PET/EVA/Si solar cell/EVA/film for lamination, -fabric/EVA/Si solar cell/EVA/tempered glass, were investigated taking into consideration type of fabric and lamination process together with the size of solar cells. In investigated devices EVA, it is ethylene-vinyl acetate, while PET - polyethylene terephthalate. Depend on the lamination process and compatibility of textile with solar cell an efficiency of investigated flexible silicon solar cells was in the range of 9.44-16.64 %. Multi folding and unfolding of flexible module has no impact on its efficiency as was detected by Instron equipment. Power (P) of constructed solar module is 30 W, while voltage about 36 V. Finally, solar panel contains five modules with the polyamide fabric and tempered glass will be produced commercially for different applications (dual use).

Keywords: flexible devices, mechanical properties, silicon solar cells, textiles

Procedia PDF Downloads 161

Authors: Sanjay Patil, Shakil A. Kagzi, Harit K. Raval

Abstract:

Tailor Welded Blanks (TWB) are utilized in automotive industries widely because of their advantage of weight and cost reduction and maintaining required strength and structural integrity. TWB consist of two or more sheet having dissimilar or similar material and thickness; welded together to form a single sheet before forming it to desired shape. Forming of the tailor welded blank is affected by ratio of thickness of blanks, ratio of their strength, etc. mainly due to in-homogeneity of material. In the present work the relative effect of these parameters on weld line movement is studied during deep drawing of TWB using FE simulation using HYPERWORKS. The simulation is validated with results from the literature. Simulations were than performed based on Taguchi orthogonal array followed by the ANOVA analysis to determine the significance of these parameters on forming of TWB.

Keywords: ANOVA, deep drawing, Tailor Welded Blank (TWB), weld line movement

Procedia PDF Downloads 296

Authors: Enjie Xu, Zhen Huang, Kunpeng Zhu, Jianping Hu, Xiaolong Ma, Yongjie Wang, Jiazhuang Zhu, Chunlin Zhang

Abstract:

Abstract: Hypoxia and dedifferentiation of osteosarcoma (OS) cells leads to poor prognosis. We plan to identify the role of hypoxia on dedifferentiation and the associated signaling pathways. We performed a sphere formation assay and determined spheroid cells as dedifferentiated cells by detecting stem cell-like markers. RNAi assay was used to explore the expression relationship between hypoxia inducible factor 1 subunit alpha (HIF1A) and platelet derived growth factor receptor beta (PDGFRB). We obtained PDGFRB knockdown and overexpression cells through lentiviral infection experiments and the effects of PDGFRB on cytoskeleton rearrangement and cell adhesion were explored by immunocytochemistry. Wound-healing experiments, transwell assays, and animal trials were employed to investigate the effect of PDGFRB on OS metastasis. Dedifferentiated OS cells were found to exhibit high expression of HIF1A and PDGFRB, and HIF1A promoted the expression of PDGFRB, subsequently activated ras homolog family member A (RhoA), and increased the phosphorylation of myosin light chain (MLC). PDGFRB also enhanced the phosphorylation of focal adhesion kinase (FAK). The OS cell morphology and vinculin distribution were altered by PDGFRB. PDGFRB also promoted cell dedifferentiation and had a significant impact on the metastasis of OS cells both in vitro and in vivo. Our results demonstrated that HIF1A up-regulated PDGFRB under hypoxic conditions, and PDGFRB regulated the actin cytoskeleton by activating RhoA and subsequently phosphorylating MLC, thereby promoting OS dedifferentiation and pulmonary metastasis.

Keywords: osteosarcoma, dedifferentiation, metastasis, cytoskeleton rearrangement, PDGFRB, hypoxia

Procedia PDF Downloads 33

Authors: Loubna Tani, Nabih Elouzzani

Abstract:

Crosstalk among interconnects and printed-circuit board (PCB) traces is a major limiting factor of signal quality in high-speed digital and communication equipments especially when fast data buses are involved. Such a bus is considered as a planar multiconductor transmission line. This paper will demonstrate how the finite difference time domain (FDTD) method provides an exact solution of the transmission-line equations to analyze the near end and the far end crosstalk. In addition, this study makes it possible to analyze the rise time effect on the near and far end voltages of the victim conductor. The paper also discusses a statistical analysis, based upon a set of several simulations. Such analysis leads to a better understanding of the phenomenon and yields useful information.

Keywords: multiconductor transmission line, crosstalk, finite difference time domain (FDTD), printed-circuit board (PCB), rise time, statistical analysis

Procedia PDF Downloads 416

Authors: Elmahdi Mohammadine, Ahouzi Esmail, Najid Abdellah

Abstract:

This contribution aims to present a new protected hybrid WDM/TDM PON architecture using Wavelength Selective Switches and Optical Line Protection devices. The objective from using these technologies is to improve flexibility and enhance the protection of GPON networks.

Keywords: Wavlenght Division Multiplexed Passive Optical Network (WDM-PON), Time Division Multiplexed PON (TDM-PON), architecture, Protection, Wavelength Selective Switches (WSS), Optical Line Protection (OLP)

Procedia PDF Downloads 521

Authors: Malte Schilling, Mahmoud M. Rabah, Sven Liebisch

Abstract:

Wave run-up and overtopping are the relevant parameters for the dimensioning of the crest height of dikes. Various experimental as well as numerical studies have investigated these parameters under different boundary conditions (e.g. wave conditions, structure type). Particularly for the dike design in Europe, a common approach is formulated where wave and structure properties are parameterized. However, this approach assumes equal run-up heights and overtopping discharges along the longitudinal axis. However, convex dikes have a heterogeneous crest by definition. Hence, local differences in a convex dike line are expected to cause wave-structure interactions different to a straight dike. This study aims to assess both run-up and overtopping at convexly curved dikes. To cast light on the relevance of curved dikes for the design approach mentioned above, physical model tests were conducted in a 3D wave basin of the Ludwig-Franzius-Institute Hannover. A dike of a slope of 1:6 (height over length) was tested under both regular waves and TMA wave spectra. Significant wave heights ranged from 7 to 10 cm and peak periods from 1.06 to 1.79 s. Both run-up and overtopping was assessed behind the curved and straight sections of the dike. Both measurements were compared to a dike with a straight line. It was observed that convex curvatures in the longitudinal dike line cause a redirection of incident waves leading to a concentration around the center point. Measurements prove that both run-up heights and overtopping rates are higher than on the straight dike. It can be concluded that deviations from a straight longitudinal dike line have an impact on design parameters and imply uncertainties within the design approach in force. Therefore, it is recommended to consider these influencing factors for such cases.

Keywords: convex dike, longitudinal curvature, overtopping, run-up

Procedia PDF Downloads 279

Authors: Zhaopeng Xuan, Yuan Bian, C. Cailleaux, Jing Qin, S. Traore

Abstract:

Traditional software engineering allows engineers to propose to their clients multiple specialized software distributions assembled from a shared set of software assets. The management of these assets however requires a trade-off between client satisfaction and software engineering process. Clients have more and more difficult to find a distribution or components based on their needs from all of distributed repositories. This paper proposes a software engineering for a user-driven software product line in which engineers define a feature model but users drive the actual software distribution on demand. This approach makes the user become final actor as a release manager in software engineering process, increasing user product satisfaction and simplifying user operations to find required components. In addition, it provides a way for engineers to manage and assembly large software families. As a proof of concept, a user-driven software product line is implemented for eclipse, an integrated development environment. An eclipse feature model is defined, which is exposed to users on a cloud-based built platform from which clients can download individualized Eclipse distributions.

Keywords: software product line, model-driven development, reverse engineering and refactoring, agile method

Procedia PDF Downloads 415

Authors: Mahbuba Rahman, Sabri Boughorbel, Scott Presnell, Charlie Quinn, Darawan Rinchai, Damien Chaussabel, Nico Marr

Abstract:

Collections of large-scale datasets made available in public repositories can be used to identify and fill gaps in biomedical knowledge. But first, these data need to be made readily accessible to researchers for analysis and interpretation. Here a collection of transcriptome datasets was made available to investigate the functional programming of human hematopoietic cells in early life. Thirty two datasets were retrieved from the NCBI Gene Expression Omnibus (GEO) and loaded in a custom, interactive web application called the Gene Expression browser (GXB), designed for visualization and query of integrated large-scale data. Multiple sample groupings and gene rank lists were created based on the study design and variables in each dataset. Web links to customized graphical views can be generated by users and subsequently be used to graphically present data in manuscripts for publication. The GXB tool also enables browsing of a single gene across datasets, which can provide information on the role of a given molecule across biological systems. The dataset collection is available online. As a proof-of-principle, one of the datasets (GSE25087) was re-analyzed to identify genes that are differentially expressed by regulatory T cells in early life. Re-analysis of this dataset and a cross-study comparison using multiple other datasets in the above mentioned collection revealed that PMCH, a gene encoding a precursor of melanin-concentrating hormone (MCH), a cyclic neuropeptide, is highly expressed in a variety of other hematopoietic cell types, including neonatal erythroid cells as well as plasmacytoid dendritic cells upon viral infection. Our findings suggest an as yet unrecognized role of MCH in immune regulation, thereby highlighting the unique potential of the curated dataset collection and systems biology approach to generate new hypotheses which can be tested in future mechanistic studies.

Keywords: early-life, GEO datasets, PMCH, interactive query, systems biology

Procedia PDF Downloads 278

Authors: Jung Park, Anca Mazare, Klaus Von Der Mark, Patrik Schmuki

Abstract:

In clinical application of TiO2 implants on tooth and hip replacement, migration, adhesion and differentiation of neighboring mesenchymal stem cells onto implant surfaces are critical steps for successful bone regeneration. In a recent decade, accumulated attention has been paid on nanoscale electrochemical surface modifications on TiO2 layer for improving bone-TiO2 surface integration. We generated, on titanium surfaces, self-assembled layers of vertically oriented TiO2 nanotubes with defined diameters between 15 and 100 nm and here we show that mesenchymal stem cells finely sense TiO2 nanotubular geometry and quickly decide their cell fate either to differentiation into osteoblasts or to programmed cell death (apoptosis) on TiO2 nanotube layers. These cell fate decisions are critically dependent on nanotube size differences (15-100nm in diameters) of TiO2 nanotubes sensing by integrin clustering. We further demonstrate that nanoscale topography-sensing is feasible not only in mesenchymal stem cells but rather seems as generalized nanoscale microenvironment-cell interaction mechanism in several cell types composing bone tissue network including osteoblasts, osteoclast, endothelial cells and hematopoietic stem cells. Additionally we discuss the synergistic effect of simultaneous stimulation by nanotube-bound growth factor and nanoscale topographic cues on enhanced bone regeneration.

Keywords: TiO2 nanotube, stem cell fate decision, nano-scale microenvironment, bone regeneration

Procedia PDF Downloads 417

Authors: J. L. Liu, L. Wang, B. Zhu, J. Zhou, W. D. Gao

Abstract:

Fabric textures are very common in our daily life. However, we never explore the representation of fabric textures from neuroscience view. Theoretical studies suggest that primary visual cortex (V1) uses a sparse code to efficiently represent natural images. However, how the simple cells in V1 encode the artificial textures is still a mystery. So, here we will take fabric texture as stimulus to study the response of independent component analysis that is established to model the receptive field of simple cells in V1. Experimental results based on 140 classical fabric images indicate that the receptive fields of simple cells have obvious selectivity in orientation, frequency, and phase when drifting gratings are used to determine their tuning properties. Additionally, the distribution of optimal orientation and frequency shows that the patch size selected from each original fabric image has a significant effect on the frequency selectivity.

Keywords: fabric texture, receptive filed, simple cell, spare coding

Procedia PDF Downloads 453

Authors: Ali Mashayekh, Mahdiye Khorasani, Thomas Weyh

Abstract:

The tendency to use the Battery-Electric vehicle (BEV) for the low and medium driving range or even high driving range has been growing more and more. As a result, higher safety, reliability, and durability of the battery pack as a component of electric vehicles, which has a great share of cost and weight of the final product, are the topics to be considered and investigated. Battery aging can be considered as the predominant factor regarding the reliability and durability of BEV. To better understand the aging process, offline battery characterization has been widely used, which is time-consuming and needs very expensive infrastructures. This paper presents the substitute method for the conventional battery characterization methods, which is based on battery Modular Multilevel Management (BM3). According to this Topology, the battery cells can be drained and charged concerning their capacity, which allows varying battery pack structures. Due to the integration of the power electronics, the output voltage of the battery pack is no longer fixed but can be dynamically adjusted in small steps. In other words, each cell can have three different states, namely series, parallel, and bypass in connection with the neighbor cells. With the help of MATLAB/Simulink and by using the BM3 modules, the battery string model is created. This model allows us to switch two cells with the different SoC as parallel, which results in the internal balancing of the cells. But if the parallel switching lasts just for a couple of ms, we can have a perturbation pulse which can stimulate the cells out of the relaxation phase. With the help of modeling the voltage response pulse of the battery, it would be possible to characterize the cell. The Online EIS method, which is discussed in this paper, can be a robust substitute for the conventional battery characterization methods.

Keywords: battery characterization, SoH estimation, RLS, BEV

Procedia PDF Downloads 134

Authors: Maryam Zahmatkesh

Abstract:

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

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

Procedia PDF Downloads 291

Authors: Arunas Stirke, Neringa Bakute, Gatis Mozolevskis

Abstract:

A technology of microfluidics is an emerging tool in the field of biology, medicine and chemistry. Microfluidic device is also known as ‘lab-on-a-chip’ technology [1]. In moving from macro- to microscale, there is unprecedented control over spatial and temporal gradients and patterns that cannot be captured in conventional Petri dishes and well plates [2]. However, there is not a single standard microfluidic chip designated for all purposes – every different field of studies needs a specific microchip with certain geometries, inlet/outlet, channel depth and other parameters to precisely regulate the required function. Since our group is studying an effect of pulsed electric field (PEF) to the cells, we have manufactured a microfluidic chip designated for high-throughput electroporation of cells. In our microchip, a cell culture chamber is divided into two parallel channels by a membrane, meanwhile electrodes for electroporation are attached to the wall of the channels. Both microchannels have their own inlet and outlet, enabling injection of transfection material separately. Our perspective is to perform electroporation of mammalian cells in two different ways: (1) plasmid and cells are injected in the same microchannel and (2) injected into separate microchannels. Moreover, oxygen and pH sensors are integrated on order to analyse cell viability parameters after PEF treatment.

Keywords: microfluidics, chip, fabrication, electroporation

Procedia PDF Downloads 63

Authors: Nithya Devi

Abstract:

Poverty, hunger and water scarcity are threats to human rights and are assaults on human dignity. The very existence of man is questioned when his basic rights are violated. Addressing this social phenomenon should be a key objective of any human rights discourse. The origins of these problems have various root causes. For Asia, colonisation was an essential factor that caused great inequalities in the distribution of wealth. In the post-colonial era, the colonised states were developing nations grappling with these issues. Today, some of the developing states have progressed to developed nations. However, others remain as economically vulnerable countries. Within states, the widening income gap poses further threat to human rights. Hence ASEAN states have prioritised socio-economic rights, particularly basic needs, in the human rights discourse in this region. To date, poverty and development goals are given primary importance. This paper seeks to show how a human rights approach has dealt with poverty and development goals in this region and evaluates its effectiveness in addressing these concerns.

Keywords: ASEAN, development, human rights, poverty

Procedia PDF Downloads 332

Authors: Vanja Misic, Mohamed El-Mogy, Yousef Haj-Ahmad

Abstract:

Endonuclease G (EndoG) is a well conserved mitochondrio-nuclear nuclease with dual lethal and vital roles in the cell. The aim of our study was to examine whether EndoG exerts its nuclease activity on exogenous DNA substrates such as plasmid DNA (pDNA), considering their importance in gene therapy applications. The effects of EndoG knockdown on pDNA stability and levels of encoded reporter gene expression were evaluated in the cervical carcinoma HeLa cells. Transfection of pDNA vectors encoding short-hairpin RNAs (shRNAs) reduced levels of EndoG mRNA and nuclease activity in HeLa cells. In physiological circumstances, EndoG knockdown did not have an effect on the stability of pDNA or the levels of encoded transgene expression as measured over a four day time-course. However, when endogenous expression of EndoG was induced by an extrinsic stimulus, targeting of EndoG by shRNA improved the perceived stability and transgene expression of pDNA vectors. Therefore, EndoG is not a mediator of exogenous DNA clearance, but in non-physiological circumstances it may non-specifically cleave intracellular DNA regardless of its origin. These findings make it unlikely that targeting of EndoG is a viable strategy for improving the duration and level of transgene expression from non-viral DNA vectors in gene therapy efforts.

Keywords: EndoG, silencing, exogenous DNA stability, HeLa cells

Procedia PDF Downloads 447

Authors: J. Harrison Kurunathan, R. Jayaparvathy

Abstract:

"Assistive Robotics" is the field that deals with the study of robots that helps in human motion and also empowers human abilities by interfacing the robotic systems to be manipulated by human motion. The proposed model is a robotic arm that works as a haptic interface on the basis on accelerometers and DC motors that will function with respect to the movement of the human muscle. The proposed model would effectively work as a haptic interface that would reduce human effort in the field of defense and rescue. This can be used in very critical conditions like fire accidents to avoid causalities.

Keywords: accelerometers, haptic interface, servo motors, signal processing

Procedia PDF Downloads 372

Authors: Sarah Crawford, Gerry Lesley

Abstract:

This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

Procedia PDF Downloads 51

Authors: Khairy Mohamed Abdalla Zoheir

Abstract:

One of the most severe complications of Rheumatoid arthritis is delayed recovery. lipoic acid possesses antioxidant, hypoglycemic, and anti-inflammatory activity. In the present study, the effects of lipoic acid were investigated on the key mediators of Rheumatoid arthritis, namely, CD4+CD25+ T cell subsets, GITR expressing cells, CD4+CD25+Foxp3+ regulatory T (Treg) cells, T-helper-17 (Th17) cells and pro-inflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor- α (TNF-α)] through flow-cytometry and qPCR analyses. Lipoic acid-treated mice showed a significant decrease in Rheumatoid arthritis, the frequency of GITR-expressing cells, and Th1 cytokines (IL-17A, TNF-αand Interferon- γ (IFN-γ) compared with positive and negative controlled mice. Lipoic acid treatment also downregulated the mRNA expression of the inflammatory mediators compared with the Rheumatoid arthritis mouse model and untreated mice. The number of Tregs was also found to be significantly upregulated in lipoic acid-treated mice. Our results were confirmed by the histopathological examination. This study showed the beneficial role of lipoic acid in promoting a well-balanced tool for the therapy of Rheumatoid arthritis.

Keywords: lipoic acid, inflammatory markers, rheumatoid arthritis, qPCR

Procedia PDF Downloads 80

Authors: Mohammad Reza Ebrahimi

Abstract:

In new restructured power systems, swift fault detection is very important. The parallel transmission-lines are vastly used in this kind of power systems because of high amount of energy transferring. In this paper, a method based on the comparison of two schemes, i.e., i) maximum magnitude of travelling-wave (TW) energy ii) the instants of maximum energy occurrence at the circuits of parallel transmission-line is proposed. Using the travelling-wave of fault in order to faulted line identification this method has noticeable operation time. Moreover, the algorithm can cover for identification of faults as external or internal faults. For an internal fault, the exact location of the fault can be estimated confidently. A lot of simulations have been done with PSCAD/EMTDC to verify the performance of the proposed algorithm.

Keywords: travelling-wave, maximum energy, parallel transmission-line, fault location

Procedia PDF Downloads 169

Authors: Muhammad Ilham Agus Salim

Abstract:

This study aims to reconstruct the discourse of human rights which focused on the issue of freedom of religion/belief (FORB) in Indonesia. This topic always has an appeal considering the development of Islam, both as a phenomenon of religion as well as social and political phenomenon, always in touch with human rights issues. For the majority, Islam is involved in human rights discourse needs to be viewed as a natural thing as it also occurs in the majority group in other countries. The natural state is increasingly gaining affirmation when also considering the doctrine of Islam which is also related to human rights. So the involvement of Islamic parties to human rights talks in Indonesia is not as excessive when considering the sociological position and character of Islamic doctrine. But because of who made the object of conversation, namely human rights and particularly freedom of religion or belief again, not something that is taken for granted, then the diversity within Islam itself impossible can be avoided. In this study the diversity of views presented in the trial which categorically can be grouped into two views, namely: inclusive and exclusive.

Keywords: Islam doctrine, Islamic parties, human rights, freedom of religion

Procedia PDF Downloads 583

Authors: Nandhakumar Elumalai, Purushothaman Ayyakannu, Sachidanandam T. Panchanatham

Abstract:

Background: Understanding the basic mechanisms and factors underlying the tumor growth and invasion has gained attention in recent times. The processes of angiogenesis and apoptosis are known to play a vital role in various stages of cancer. The vascular endothelial growth factor (VEGF) is well established as one of the key regulators of tumor angiogenesis while MMPs are known for their exclusive ability to degrade ECM. Objective: The present study was designed to evaluate the pro apoptotic and anti angiogenic activity of the herbal formulation Shemamruthaa. The anticancer activity of Shemamruthaa was tested in breast cancer cell line (MCF-7). Results of MTT, trypan blue and flow cytometric analysis of apoptotis suggested that Shemamruthaa can induce cytotoxicity in cancer cells, in a concentration- and time dependent manner and induce apoptosis. With these results, we further evaluated the antiangiogenic and pro-apoptotic activities of Shemamruthaa in DMBA induced mammary carcinoma in Sprague Dawley rats. Flavono tumour was induced in 8-week-old Sprague-Dawley rats by gastric intubation of 25 mg DMBA in 1ml olive oil. After 90 days of induction period, the rats were orally administered with Shemamruthaa (400 mg/kg body wt) for 45 days. Treatment with the drug SM significantly modulated the expression of p53, MMP-2, MMP-3, MMP-9 and VEGF by means of its anti angiogenic and protease inhibiting activity. Conclusion: Based on these results, it might be concluded that the formulation, Shemamruthaa, constituted of dried flowers of Hibiscus rosa-sinensis, fruits of Emblica officinalis, and honey has been found to exhibit pronounced antiproliferative and apoptotic effects. This enhanced anticancer effect of Shemamruthaa might be attributed to the synergistic action of polyphenols such as flavonoids, tannins, alkaloids, glycosides, saponins, steroids, terpenoids, vitamin C, niacin, pyrogallol, hydroxymethylfurfural, trilinolein, and other compounds present in the formulation. Collectively, these results demonstrate that Shemamruthaa holds potential to be developed as a potent chemotherapeutic agent against mammary carcinoma.

Keywords: Shemamruthaa, flavonoids, MCF-7 cell line, mammary cancer

Procedia PDF Downloads 235

Authors: Nazanin Amanat, Alison Tayler, Steve Whyard

Abstract:

While chemical insecticides effectively control many insect pests, they also harm many non-target species. Double-stranded RNA (dsRNA) pesticides, in contrast, can be designed to target unique gene sequences and thus act in a species-specific manner. DsRNA insecticides do not, however, work equally well for all insects, and for some species that are considered refractory to dsRNA, a primary factor affecting efficacy is the relative ease by which dsRNA can enter a target cell’s cytoplasm. In this study, we are examining how different structured dsRNAs (linear, hairpin, and paperclip) can enter mosquito and lepidopteran cells, as they represent dsRNA-sensitive and refractory species, respectively. To determine how the dsRNAs enter the cells, we are using chemical inhibitors and RNA interference (RNAi)-mediated knockdown of key proteins associated with different endocytosis processes. Understanding how different dsRNAs enter cells will ultimately help in the design of molecules that overcome refractoriness to RNAi or develop resistance to dsRNA-based insecticides. To date, we have conducted chemical inhibitor experiments on both cell lines and have evidence that linear dsRNAs enter the cells using clathrin-mediated endocytosis, while the paperclip dsRNAs (pcRNAs) can enter both species’ cells in a clathrin-independent manner to induce RNAi. An alternative uptake mechanism for the pcRNAs has been tentatively identified, and the outcomes of our RNAi-mediated knockdown experiments, which should provide corroborative evidence of our initial findings, will be discussed.

Keywords: dsRNA, RNAi, uptake, insecticides, dipteran, lepidopteran

Procedia PDF Downloads 54

Authors: Kimberly McCabe

Abstract:

The trafficking of women and children for abuse and exploitation is not a new problem under the umbrella of human trafficking; however, over the last decade, the problem has attracted increased attention from international governments and non-profits attempting to reduce victimization and provide services for survivors. Research on human trafficking suggests that the trafficking of human beings is, largely, a symptom of poverty. As the trafficking of human beings may be viewed as a response to the demand for people for various forms of exploitation, a product of poverty, and a consequence of the subordinate positions of women and children in society, it reaches beyond randomized victimization. Hence, human trafficking, and especially the trafficking of women and children, goes beyond the realm of poorness. Therefore, to begin to understand the reasons for the existence of human trafficking, one must identify and consider not only the immediate causes but also those underlying structural determinants that facilitate this form of victimization. Specifically, one must acknowledge the economic, social, and cultural factors that support human trafficking. This research attempts to study human trafficking at the country level by focusing on economic, social, and cultural characteristics. This study focuses on inequality and, in particular, gender inequality as related to legislative attempts to address human trafficking. Within the design of this project is the use of the US State Department’s tier classification system for Trafficking in Persons (TIP) and the USA CIA Fact Sheet of country characteristics for over 150 countries in an attempt to model legal outcomes as related to human trafficking. Results of this research demonstrate the significance of characteristics beyond poverty as related to country-level responses to human trafficking.

Keywords: child trafficking, gender inequality, human trafficking, inequality

Procedia PDF Downloads 210

Authors: M. Pourshirazi, M. Esmaelifar, A. Aliahmadi, F. Yazdian, A. S. Hatamian Zarami, S. J. Ashrafi

Abstract:

Medicinal fungi are the new potential source of drugs to improve the treatment of diseases with association to oxidative agents such as cancers. Monascus purpureus contains functional components potentially effective in improving human health. In the present work, ethanolic extract of Monascus purpureus (EEM) was evaluated for health improving potential mainly focusing on antioxidant and anticancer activities. Ferric ion reducing power (FRAP), scavenging of DPPH radicals and determining viability of breast carcinoma MCF-7 and cervical carcinoma HeLa cells with MTT assay were evaluated. Our data showed a significant antioxidant activity of EEM with 142.45 µg/ml inhibition concentration of 50% DPPH radicals and 2112.33 µg eq.Fe2+/mg extract of FRAP assay. These results might be caused by antioxidant components such as pigments and phenolic compounds. Further, the results demonstrated that EEM caused significant reduction in the viability of MCF-7 with IC50 of 7 µg/ml but not have good effect against viability of HeLa cells. Accordingly, Monascus purpureus is presented as a strong potential of breast cancer treatment. In further study, the mechanistic studies are needed to determine the mechanisms of anticancer activity of EEM.

Keywords: Monascus purpureus, antioxidant, cancer, ethanolic extract

Procedia PDF Downloads 393

Authors: Stephen Adeniyi Adefegha, Vitor Mostardeiro, Vera Maria Morsch, Ademir F. Morel, Ivana Beatrice Manica Da Cruz, Sabrina Somacal Maria Rosa Chitolina Schetinger

Abstract:

Moringa stenopetala is often consumed as food and used in folkloric medicine for the management of several diseases. Purpose: This study was set up in order to assess the effect of aqueous extract of Moringa stenopetala on cell viability and oxidative stress biomarkers in BV-2 microglial cells. Aqueous extracts of M. stenopetala were prepared, lyophilized and reconstituted in 0.5% dimethylsulphoxide (DMSO). Cells were treated with M. stenopetala extracts (0.1 - 100 µg/ml) for cell viability and nitric oxide (NO) production tests. However, M. stenopetala extract (50 µg/ml) was used in the treatment of cells for the determination of protein carbonyl content and reactive oxygen species (ROS) level. Incubation of BV-2 microglia cell with M. stenopetala extract maintained cell viability, diminished NO and ROS levels, and reduced protein carbonyl contents Chlorogenic acid, rutin, kaempferol and quercetin derivatives were the main phenolic compounds identified in M. stenopetala leaf extract. These phenolic compounds present in M. stenopetala may be responsible for the mitigation of oxidative stress in BV-2 microglial cells.

Keywords: oxidative stress, BV-2 microglial cell, Moringa stenopetala, cell viability, antioxidant

Procedia PDF Downloads 94

Authors: Svitlana Antonenko, Gennady Telegeev

Abstract:

Introductive statement: The development of chronic myeloid leukemia (CML) is caused by Bcr-Abl oncoprotein. Modern treatments with tyrosine kinase inhibitors are greatly complicated by the mutational variability of the Bcr-Abl oncoprotein, which causes drug resistance. Therefore, there is an urgent need to develop new approaches to the treatment of the disease, which will allow modeling the level of Bcr-Abl oncoprotein in the cell. Promising in this direction is the identification of proteases that can selectively promote cellular proteolysis of oncoproteins. The aim of the study was to study the effect of the interaction of Bcr-Abl with deubiquitinase USP1 on the level of oncoprotein in CML cells. Methodology: K562 cells were selected for the experiment. Сells were incubated with ML323 inhibitor for 24 hours. Precipitation of endogenous proteins from K562 cell lysate was performed using anti-Bcr-Abl antibodies. Cell lysates and precipitation results were studied by Western blot. Subcellular localization of proteins was studied by immunofluorescence analysis followed by confocal microscopy. The results were analyzed quantitatively and statistically. Major findings: The Bcr-Abl/USP1 protein complex was detected in CML cells, and it was found that inhibition of USP1 deubiquitinating activity by the compound ML323 leads to disruption of this protein complex and a decrease in the level of Bcr-Abl oncoprotein in cells. The interaction of Bcr-Abl with USP1 may result in deubiquitination of the oncoprotein, which disrupts its proteasomal degradation and leads to the accumulation of CML in cells. Conclusion: We believe that the interaction of oncoprotein with USP1 may be one of the prerequisites that contribute to malignant cell transformation due to the deubiquitination of oncoprotein, which leads to its accumulation and disease progression. A correlation was found between the deubiquitinating activity of USP1 and the level of oncoprotein in CML cells. Thus, we identify deubiquitinase USP1 as a promising therapeutic target for the development of a new strategy for the treatment of CML by modulating the level of Bcr-Abl in the cell.

Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, deubiquitination Bcr-Abl, K562 cell

Procedia PDF Downloads 51

Authors: Tholaine Matadi

Abstract:

South Africa is a democratic country with a historical record of racially-motivated marginalisation and exclusion of the majority. During the apartheid era the country was run along pieces of legislation and policies based on racial segregation. The system held a tight clamp on interracial mixing which forced people to remain in segregated areas. For example, a citizen from the Indian community could not own property in an area allocated to white people. In this way, a great majority of people were denied basic human rights. Now, there is a supreme constitution with an entrenched justiciable Bill of Rights founded on democratic values of social justice, human dignity, equality and the advancement of human rights and freedoms. The Constitution also enshrines the values of non-racialism and non-sexism. The Constitutional Court has the power to declare unconstitutional any law or conduct considered to be inconsistent with it. Now, more than two decades down the line, despite the abolition of apartheid, there is evidence that South Africa still experiences hate crimes which violate the entrenched right of vulnerable groups not to be discriminated against on the basis of race, sexual orientation, gender, national origin, occupation, or disability. To remedy this mischief parliament has responded by drafting the Prevention and Combatting of Hate Crimes and Hate Speech Bill. The Bill has been disseminated for public comment and suggestions. It is intended to combat hate crimes and hate speech based on sheer prejudice. The other purpose of the Bill is to bring South Africa in line with international human rights instruments against racism, racial discrimination, xenophobia and related expressions of intolerance identified in several international instruments. It is against this backdrop that this paper intends to analyse the impact of the Bill on the rights to human dignity, equality, and freedom. This study is significant because the Bill was highly contested and creates a huge debate. This study relies on a qualitative evaluative approach based on desktop and library research. The article recurs to primary and secondary sources. For comparative purpose, the paper compares South Africa with countries such as Australia, Canada, Kenya, Cuba, and United Kingdom which have criminalised hate crimes and hate speech. The finding from this study is that despite the Bill’s expressed positive intentions, this draft legislation is problematic for several reasons. The main reason is that it generates considerable controversy mostly because it is considered to infringe the right to freedom of expression. Though the author suggests that the Bill should not be rejected in its entirety, she notes the brutal psychological effect of hate crimes on their direct victims and the writer emphasises that a legislature can succeed to combat hate-crimes only if it provides for them as a separate stand-alone category of offences. In view of these findings, the study recommended that since hate speech clauses have a negative impact on freedom of expression it can be promulgated, subject to the legislature enacting the Prevention and Combatting of Hate-Crimes Bill as a stand-alone law which criminalises hate crimes.

Keywords: freedom of expression, hate crimes, hate speech, human dignity

Procedia PDF Downloads 150

Authors: Ni Komang Desy Arya Pinatih

Abstract:

Transnational crime is a crime with 'unique' feature because the activities benefit the lack of state monitoring on the borders so dealing with it cannot be based on conventional engagement but also need joint operation with other countries. On the other hand with the flow of globalization and the growth of information technology and transportation, states become more vulnerable to transnational crime threats especially human trafficking. This paper would examine transnational crime activities, especially human trafficking in Indonesia. With the case study on the mapping of human trafficking crime in East Java province, Indonesia, this paper would try to analyze how the difference in human trafficking crime trends at the national and sub-national levels. The findings of this research were first, there is difference in human trafficking crime trends whereas at the national level the trend is rising, while at sub-national (province) level the trend is declining. Second, regarding the decline of human trafficking number, it’s interesting to see how the method to decrease human trafficking crime in East Jawa Province in order to reduce transnational crime accounts in the region. These things are hopefully becoming a model for transnational crimes engagement in other regions to reduce human trafficking numbers as much as possible.

Keywords: transnational crime, human trafficking, southeast Asia, anticipation model on transnational crimes

Procedia PDF Downloads 280