Search results for: active targeting
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4166

Search results for: active targeting

3506 Developing the Involvement of Nurses in Determining Health Policies

Authors: Yafa Haron, Hanna Adami

Abstract:

Background: World Health Organization emphasizes the contribution of nurses in planning and implementing health policies and reforms. Aim: To evaluate nursing students’ attitudes towards nurses’ involvement in health policy issues. Methods: Mixed-methods; qualitative and quantitative – a descriptive study. Participants - nursing students who were enrolled in their last year in the undergraduate program (BSN). Qualitative data included two open-ended questions: What is health policy and what is the importance of studying health policy, and 18 statements on the Likert Scale range 1-5. Results: Qualitativeanalysisrevealed that the majority of students defined health policy as a set of rules and regulations that defined procedures, borders, and proper conduct. 73% of students responded that nurses should be active in policymaking, but only 22% thought that nurses were currently involved in political issues. 28% thought that nurses do not have the knowledge and the time needed (60%) for political activity. 77% thought that the work environment did not encourage nurses to be politically active. Nursing students are aware of the importance towards nurses’ involvement in health policy issues, however, they do not have role models based on their low evaluation regarding nurses’ involvement in the health policy decision making process at the local or national level. Conclusions: Results emphasize the importance and the need of implementation the recommendation to include “advance policy changes” as core competency in nursing education and practice.

Keywords: health policy, nursing education, health systems, student perceptions

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3505 Improve Divers Tracking and Classification in Sonar Images Using Robust Diver Wake Detection Algorithm

Authors: Mohammad Tarek Al Muallim, Ozhan Duzenli, Ceyhun Ilguy

Abstract:

Harbor protection systems are so important. The need for automatic protection systems has increased over the last years. Diver detection active sonar has great significance. It used to detect underwater threats such as divers and autonomous underwater vehicle. To automatically detect such threats the sonar image is processed by algorithms. These algorithms used to detect, track and classify of underwater objects. In this work, divers tracking and classification algorithm is improved be proposing a robust wake detection method. To detect objects the sonar images is normalized then segmented based on fixed threshold. Next, the centroids of the segments are found and clustered based on distance metric. Then to track the objects linear Kalman filter is applied. To reduce effect of noise and creation of false tracks, the Kalman tracker is fine tuned. The tuning is done based on our active sonar specifications. After the tracks are initialed and updated they are subjected to a filtering stage to eliminate the noisy and unstable tracks. Also to eliminate object with a speed out of the diver speed range such as buoys and fast boats. Afterwards the result tracks are subjected to a classification stage to deiced the type of the object been tracked. Here the classification stage is to deice wither if the tracked object is an open circuit diver or a close circuit diver. At the classification stage, a small area around the object is extracted and a novel wake detection method is applied. The morphological features of the object with his wake is extracted. We used support vector machine to find the best classifier. The sonar training images and the test images are collected by ARMELSAN Defense Technologies Company using the portable diver detection sonar ARAS-2023. After applying the algorithm to the test sonar data, we get fine and stable tracks of the divers. The total classification accuracy achieved with the diver type is 97%.

Keywords: harbor protection, diver detection, active sonar, wake detection, diver classification

Procedia PDF Downloads 237
3504 Biological Activities of Flaxseed Peptides (Linusorbs)

Authors: Youn Young Shim, Ji Hye Kim, Jae Youl Cho, Martin J. T. Reaney

Abstract:

Flaxseed (Linum usitatissimum L.) is gaining popularity in the food industry as a superfood due to its health-promoting properties. The flax plant synthesizes an array of biologically active cyclic peptides or linusorbs (LOs, a.k.a. cyclolinopeptides) from three or more ribosome-derived precursors. [1–9-NαC]-linusorb B3 and [1–9-NαC]-linusorb B2, suppress immunity, induce apoptosis in human epithelial cancer cell line (Calu-3) cells, and inhibit T-cell proliferation, but the mechanism of LOs action is unknown. Using gene expression analysis in nematode cultures and human cancer cell lines, we have observed that LOs exert their activity, in part, through induction of apoptosis. Specific LOs’ properties include: 1) distribution throughout the body after flaxseed consumption; 2) induce heat shock protein (HSP) 70A production as an indicator of stress and address the issue in Caenorhabditis elegans (exposure of nematode cultures to [1–9-NαC]-linusorb B3 induced a 30% increase in production of the HSP 70A protein); 3) induce apoptosis in Calu-3 cells; and 4) modulate regulatory genes in microarray analysis. These diverse activities indicate that LOs might induce apoptosis in cancer cells or act as versatile platforms to deliver a variety of biologically active molecules for cancer therapy.

Keywords: flaxseed, linusorb, cyclic peptide, orbitides, heat shock protein, apoptosis, anti-cancer

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3503 Foslip Loaded and CEA-Affimer Functionalised Silica Nanoparticles for Fluorescent Imaging of Colorectal Cancer Cells

Authors: Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, Thomas Hughes, Paul Millner, David G. Jayne

Abstract:

Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.

Keywords: colorectal cancer, silica nanoparticles, Affimers, antibodies, imaging

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3502 Oncogenic Functions of Long Non-Coding RNA XIST in Human Nasopharyngeal Carcinoma by Targeting MiR-34a-5p

Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

Abstract:

Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been verified as an oncogenic gene in several human malignant tumors, and its dysregulation was closed associated with tumor initiation, development and progression. Nevertheless, whether the aberrant expression of XIST in human nasopharyngeal carcinoma (NPC) is corrected with malignancy, metastasis or prognosis has not been elaborated. Here, we discovered that XIST was up-regulated in NPC tissues and higher expression of XIST contributed to a markedly poorer survival time. In addition, multivariate analysis demonstrated XIST was an independent risk factor for prognosis. XIST over-expression enhanced, while XIST silencing hampered the cell growth in NPC. Additionally, mechanistic analysis revealed that XIST up-regulated the expression of miR-34a-5p targeted gene E2F3 through acting as a competitive ‘sponge’ of miR-34a-5p. Taking all into account, we concluded that XIST functioned as an oncogene in NPC through up-regulating E2F3 in part through ‘spongeing’ miR-34a-5p.

Keywords: X inactivate-specific transcript; hsa-miRNA-34a-5p, miR-34a-5p; E2F3, nasopharyngeal carcinoma, tumorigenesis

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3501 Clustered Regularly Interspaced Short Palindromic Repeats Interference (CRISPRi): An Approach to Inhibit Microbial Biofilm

Authors: Azna Zuberi

Abstract:

Biofilm is a sessile bacterial accretion in which bacteria adapts different physiological and morphological behavior from planktonic form. It is the root cause of about 80% microbial infections in human. Among them, E. coli biofilms are most prevalent in medical devices associated nosocomial infections. The objective of this study was to inhibit biofilm formation by targeting LuxS gene, involved in quorum sensing using CRISPRi. luxS is a synthase, involved in the synthesis of Autoinducer-2(AI-2), which in turn guides the initial stage of biofilm formation. To implement CRISPRi system, we have synthesized complementary sgRNA to target gene sequence and co-expressed with dCas9. Suppression of luxS was confirmed through qRT-PCR. The effect of luxS gene on biofilm inhibition was studied through crystal violet assay, XTT reduction assay and scanning electron microscopy. We conclude that CRISPRi system could be a potential strategy to inhibit bacterial biofilm through mechanism base approach.

Keywords: biofilm, CRISPRi, luxS, microbial

Procedia PDF Downloads 181
3500 Thermal Perception by Older People in Open Spaces in Madrid: Relationships between Weather Parameters and Personal Characteristics

Authors: María Teresa Baquero, Ester Higueras

Abstract:

One of the challenges facing 21st century cities, is their adaptation to the phenomenon of an ageing population. International policies have been developed, such as the "Global Network for Age-friendly Cities and Communities". These cities must recognize the diversity of the elderly population, and facilitate an active, healthy, satisfied aging and promote inclusion. In order to promote active and healthy aging, older people should be encouraged to engage in physical activity, sunbathe, socialize and enjoy the public open spaces in the city. Some studies recognize thermal comfort as one of the factors that most influence the use of public open spaces. However, although some studies have shown vulnerability to thermal extremes and environmental conditions in older people, there is little research on thermal comfort for older adults, because it is usually analyzed based on the characteristics of the ¨average young person¨ without considering the physiological, physical and psychological differences that characterize the elderly. This study analyzes the relationship between the microclimate parameters as air temperature, relative humidity, wind speed and sky view factor (SVF) with the personal thermal perception of older adults in three public spaces in Madrid, through a mixed methodology that combines weather measurements with interviews, made during the year 2018. Statistical test like Chi-square, Spearman, and analysis of variance were used to analyze the relationship between preference votes and thermal sensation votes with environmental and personal parameters. The results show that there is a significant correlation between thermal sensation and thermal preference with the measured air temperature, age, level of clothing, the color of clothing, season, time of the day and kind of space while no influence of gender or other environmental variables was detected. These data would contribute to the design of comfortable public spaces that improve the welfare of the elderly contributing to "active and healthy aging" as one of the 21st century challenges cities face.

Keywords: healthy ageing, older adults, outdoor public space, thermal perception

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3499 Education Delivery in Youth Justice Centres: Inside-Out Prison Exchange Program Pedagogy in an Australian Context

Authors: Tarmi A'Vard

Abstract:

This paper discusses the transformative learning experience for students participating in the Inside-Out Prison Exchange Program (Inside-out) and explores the value this pedagogical approach may have in youth justice centers. Inside-Out is a semester-long university course which is unique as it takes 15 university students, with their textbook and theory-based knowledge, behind the walls to study alongside 15 incarcerated students, who have the lived experience of the criminal justice system. Inside-out is currently offered in three Victorian prisons, expanding to five in 2020. The Inside-out pedagogy which is based on transformative dialogic learning is reliant upon the participants sharing knowledge and experiences to develop an understanding and appreciation of the diversity and uniqueness of one another. Inside-out offers the class an opportunity to create its own guidelines for dialogue, which can lead to the student’s sense of equality, which is fundamental in the success of this program. Dialogue allows active participation by all parties in reconciling differences, collaborating ideas, critiquing and developing hypotheses and public policies, and encouraging self-reflection and exploration. The structure of the program incorporates the implementation of circular seating (where the students alternate between inside and outside), activities, individual reflective tasks, group work, and theory analysis. In this circle everyone is equal, this includes the educator, who serves as a facilitator more so than the traditional teacher role. A significant function of the circle is to develop a group consciousness, allowing the whole class to see itself as a collective, and no one person holds a superior role. This also encourages participants to be responsible and accountable for their behavior and contributions. Research indicates completing academic courses, like Inside-Out, contributes positively to reducing recidivism. Inside-Out’s benefits and success in many adult correctional institutions have been outlined in evaluation reports and scholarly articles. The key findings incorporate the learning experiences for the students in both an academic capability and professional practice and development. Furthermore, stereotypes and pre-determined ideas are challenged, and there is a promotion of critical thinking and evidence of self-discovery and growth. There is empirical data supporting positive outcomes of education in youth justice centers in reducing recidivism and increasing the likelihood of returning to education upon release. Hence, this research could provide the opportunity to increase young people’s engagement in education which is a known protective factor for assisting young people to move away from criminal behavior. In 2016, Tarmi completed the Inside-Out educator training in Philadelphia, Pennsylvania, and has developed an interest in exploring the pedagogy of Inside-Out, specifically targeting young offenders in a Youth Justice Centre.

Keywords: dialogic transformative learning, inside-out prison exchange program, prison education, youth justice

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3498 The Effect of the Earthworm (Lumbricus rubellus) as the Source of Protein Feed and Pathogen Antibacterial for Broiler

Authors: Waode Nurmayani, Nikmatul Riswanda

Abstract:

Broilers are chickens which are kept with the most efficient time and hoped get a good body weight. All things are done, for example with the improvement of feed and use antibiotics. Feed cost is the most cost to be spent. Nearly 80% of the cost is spent just for buy feed. Earthworm (Lumbricus rubellus) is a good choice to reduce the cost of feed protein source. The Earthworm has a high crude protein content of about 48.5%-61.9%, rich with proline amino acid about 15% of the 62 amino acids. Not only about protein, this earthworm also has a role in disease prevention. Prevention of disease in livestock usual with use feed supplement. Earthworm (Lumbricus rubellus) is one of the natural materials used as feed. In addition, several types of earthworms that have been known to contain active substances about antibacterial pathogens namely Lumbricus rubellus. The earthworm could be used as an antibiotic because it contain the antibody of Lumbricine active substance. So that, this animal feed from Lumbricus rubellus could improve the performance of broilers. Bioactive of anti-bacterial is called Lumbricine able to inhibit the growth of pathogenic bacteria in the intestinal wall so that the population of pathogenic bacteria is reduced. The method of write in this scientific writing is divided into 3 techniques, namely data completion, data analysis, and thinking pan from various literature about earthworm (Lumbricus rubellus) as broiler feed. It is expected that innovation of feed material of earthworm (Lumbricus rubellus) could reduce the cost of protein feed and the use of chemical antibiotics.

Keywords: earthworm, broiler, protein, antibiotic

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3497 Comparison of Phenolic and Urushiol Contents of Different Parts of Rhus verniciflua and Their Antimicrobial Activity

Authors: Jae Young Jang, Jong Hoon Ahn, Jae-Woong Lim, So Young Kang, Mi Kyeong Lee

Abstract:

Rhus verniciflua is commonly known as a lacquer tree in Korea. Stem barks of R. verniciflua have been used as an immunostimulator in traditional medicine. It contains phenolic compounds and is known for diverse biological activities such as antioxidant and antimicrobial activity. However, it also causes allergic dermatitis due to urushiols derivatives. For the development of active natural resources with less toxicity, the content of phenolic compounds and urushiols of different parts of R. verniciflua such as stem barks, lignum and leaves were quantitated by colorimetric assay and HPLC analysis. The urushiols content were the highest in stem barks, and followed by leaves. The lignum contained trace amount of urushiols. The phenolic contents, however, were the most abundant in lignum, and followed by leaves and stem barks. These results clear showed that the content of urushiols and phenolic differs depending on the parts of R. verniciflua. Antimicrobial activity of different parts of R. verniciflua against fish pathogenic bacteria was also investigated using Edwardsiella tarda. Lignum of R. verniciflua was the most effective in antimicrobial activity against E. tarda and phenolic constituents are suggested to be active constituents for activity. Taken together, phenolic compounds are responsible for antimicrobial activity of R. verniciflua. The lignum of R. verniciflua contains high content of phenolic compounds with less urushiols, which suggests efficient antimicrobial activity with less toxicity. Therefore, lignum of R. verniciflua are suggested as good sources for antimicrobial activity against fish bacterial diseases.

Keywords: different parts, phenolic compounds, Rhus verniciflua, urushiols

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3496 Surface Modified Polyvinylidene Fluoride Membranes for Potential Use in Membrane Distillation

Authors: Lebea Nthunya, Arne Verliefde, Bhekie Mamba, Sabelo Mhlanga

Abstract:

A study aimed at developing membrane distillation (MD) processes that can be used for brackish/saline water purification will be presented. MD is a membrane-based technology that presents a possibility to counteract challenges associated with pressure driven membranes at high separation efficiencies. Membrane distillation membranes (MDM) are affected by wettability and fouling. Wetting inside the pores of the membrane is elevated by the hydrophilic characteristic of the membrane, while fouling is mostly induced by the hydrophobic-hydrophobic interaction of pollutants and the surface of the hydrophobic membranes, hence block the pores of the membranes. These properties are not desirable. As such, a carefully designed polyvinylidene fluoride (PVDF) MDM composed of a super-hydrophobic modified backbone and a super-hydrophilic thin layer has been developed to concurrently overcome these challenges. The membranes were characterized using contact angle measurements to confirm their hydrophobicity/hydrophilicity. SEM and SAXS were used to study the morphology and pore distribution on the surface of the membrane. The contact angles of the active surface ≤ 30º and that of the backbone ≥ 140º has thus revealed that the active surface was highly hydrophilic while the backbone was highly hydrophobic. The SEM and the SAXS results have also confirmed that the membranes are highly porous. These materials demonstrated a potential to remove salts from water at high efficiencies.

Keywords: membrane distillation, modification, energy efficiency, desalination

Procedia PDF Downloads 252
3495 Trends in Arabic Drama Series (Musalsalat) Production

Authors: Paradigm Shift

Abstract:

In an overwhelmingly import oriented content bazaar of Arabian TV industry, Musalsalat stand unique in their indigenousness and mass popularity, being rivalled only by movies and football. The Arabic term ‘Musalsalat’ stands for drama series with episodes of 30-45 minutes duration; the format being close to Latin American Telenovela concept-clear cut stories with definitive endings that permit narrative closures. Traditionally Musalsalat were either situational comedies or religiously inspired. Present-day productions have started addressing historical, creative and socially progressive issues targeting the young and well-travelled audiences. Though these soaps get prime ratings throughout the year, it is during Ramadan, that they become a raving success in securing viewership. That Musalsalat have become paramount Ramadan programming is evident by their dominance on the grid and attracting heavy ad-spend. The number of Musalsalats produced specifically for Ramadan reached over 100 last year with Ramadan TV advertising amounting to USD1, 947bn constituting 21% of the total regional TV Adspend of USD 9,189bn.

Keywords: Musalsalat, drama, pan Arab, television

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3494 Radiofrequency and Near-Infrared Responsive Core-Shell Multifunctional Nanostructures Using Lipid Templates for Cancer Theranostics

Authors: Animesh Pan, Geoffrey D. Bothun

Abstract:

With the development of nanotechnology, research in multifunctional delivery systems has a new pace and dimension. An incipient challenge is to design an all-in-one delivery system that can be used for multiple purposes, including tumor targeting therapy, radio-frequency (RF-), near-infrared (NIR-), light-, or pH-induced controlled release, photothermal therapy (PTT), photodynamic therapy (PDT), and medical diagnosis. In this regard, various inorganic nanoparticles (NPs) are known to show great potential as the 'functional components' because of their fascinating and tunable physicochemical properties and the possibility of multiple theranostic modalities from individual NPs. Magnetic, luminescent, and plasmonic properties are the three most extensively studied and, more importantly biomedically exploitable properties of inorganic NPs. Although successful attempts of combining any two of them above mentioned functionalities have been made, integrating them in one system has remained challenge. Keeping those in mind, controlled designs of complex colloidal nanoparticle system are one of the most significant challenges in nanoscience and nanotechnology. Therefore, systematic and planned studies providing better revelation are demanded. We report a multifunctional delivery platform-based liposome loaded with drug, iron-oxide magnetic nanoparticles (MNPs), and a gold shell on the surface of liposomes, were synthesized using a lipid with polyelectrolyte (layersomes) templating technique. MNPs and the anti-cancer drug doxorubicin (DOX) were co-encapsulated inside liposomes composed by zwitterionic phophatidylcholine and anionic phosphatidylglycerol using reverse phase evaporation (REV) method. The liposomes were coated with positively charge polyelectrolyte (poly-L-lysine) to enrich the interface with gold anion, exposed to a reducing agent to form a gold nanoshell, and then capped with thio-terminated polyethylene glycol (SH-PEG2000). The core-shell nanostructures were characterized by different techniques like; UV-Vis/NIR scanning spectrophotometer, dynamic light scattering (DLS), transmission electron microscope (TEM). This multifunctional system achieves a variety of functions, such as radiofrequency (RF)-triggered release, chemo-hyperthermia, and NIR laser-triggered for photothermal therapy. Herein, we highlight some of the remaining major design challenges in combination with preliminary studies assessing therapeutic objectives. We demonstrate an efficient loading and delivery system to significant cell death of human cancer cells (A549) with therapeutic capabilities. Coupled with RF and NIR excitation to the doxorubicin-loaded core-shell nanostructure helped in securing targeted and controlled drug release to the cancer cells. The present core-shell multifunctional system with their multimodal imaging and therapeutic capabilities would be eminent candidates for cancer theranostics.

Keywords: cancer thernostics, multifunctional nanostructure, photothermal therapy, radiofrequency targeting

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3493 The Effect of SIRT1 on NLRP3 (Nucleotide Oligomerization Domain-Like Receptor Family, Pyrin Domain Containing 3) Inflammasome of Osteoarthritis

Authors: So Youn Park, Yi Sle Lee, Ki Whan Hong, Chi Dae Kim

Abstract:

The role of metabolism in the pathogenesis of osteoarthritis is an emerging field. Metabolic alterations may be a role in osteoarthritis (OA) pathogenesis, and these changes influence joint destruction via several cytokine. Especially, in OA patients, levels of IL-1β are elevated in the synovial fluid, synovial membrane, subchondral bone, and cartilage. The IL-1β is activated by NLRP3 inflammasomes, and NLRP3 inflammasomes are cytosolic complexes that drive the production of other inflammatory cytokines, including IL-1β. In this study, we examined that SIRT1 suppresses IL-1β through inhibiting NLRP3 inflammasomes and SIRT1 ameliorates osteoarthritis. OA fibroblasts were isolated from synovium of OA patients. IL-1β and NLRP3 were detected in synovium of OA patients by immunohistochemistry. Lipopolysaccharides (LPS) stimulated the expression of active IL-1β mRNA in OA fibroblasts and combination of LPS, and adenosine triphosphate increased more the expression of active IL-1β in OA fibroblasts. The level of IL-1β was measured by western blot and ELISA assay. NLRP3 inflammasomes complex were measured by western blot. SIRT1 did not inhibit expression of NLRP3 inflammasome. So caspase-1, apoptotic speck-like protein containing a caspase recruitment domain (ASC) and NLRP3 protein were expressed in OA fibroblasts. But SIRT1 suppressed activation of IL-1β by inhibiting activity of caspase-1 via NLRP3 inflammasome in OA fibroblasts under LPS plus ATP stimulation. These results suggest that SIRT1 is a modulator of NLRP3 inflammasomes in OA fibroblasts and ameliorate IL-1β, so expression of SIRT1 in OA fibroblast may be a potential strategy for OA inflammation treatment.

Keywords: osteoarthritis, inflammasome, SIRT1, IL-1beta

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3492 A Simulation Study of Direct Injection Compressed Natural Gas Spark Ignition Engine Performance Utilizing Turbulent Jet Ignition with Controlled Air Charge

Authors: Siyamak Ziyaei, Siti Khalijah Mazlan, Petros Lappas

Abstract:

Compressed Natural Gas (CNG) mainly consists of Methane CH₄ and has a low carbon to hydrogen ratio relative to other hydrocarbons. As a result, it has the potential to reduce CO₂ emissions by more than 20% relative to conventional fuels like diesel or gasoline Although Natural Gas (NG) has environmental advantages compared to other hydrocarbon fuels whether they are gaseous or liquid, its main component, CH₄, burns at a slower rate than conventional fuels A higher pressure and a leaner cylinder environment will overemphasize slow burn characteristic of CH₄. Lean combustion and high compression ratios are well-known methods for increasing the efficiency of internal combustion engines. In order to achieve successful CNG lean combustion in Spark Ignition (SI) engines, a strong ignition system is essential to avoid engine misfires, especially in ultra-lean conditions. Turbulent Jet Ignition (TJI) is an ignition system that employs a pre-combustion chamber to ignite the lean fuel mixture in the main combustion chamber using a fraction of the total fuel per cycle. TJI enables ultra-lean combustion by providing distributed ignition sites through orifices. The fast burn rate provided by TJI enables the ordinary SI engine to be comparable to other combustion systems such as Homogeneous Charge Compression Ignition (HCCI) or Controlled Auto-Ignition (CAI) in terms of thermal efficiency, through the increased levels of dilution without the need of sophisticated control systems. Due to the physical geometry of TJIs, which contain small orifices that connect the prechamber to the main chamber, scavenging is one of the main factors that reduce TJI performance. Specifically, providing the right mixture of fuel and air has been identified as a key challenge. The reason for this is the insufficient amount of air that is pushed into the pre-chamber during each compression stroke. There is also the problem that combustion residual gases such as CO₂, CO and NOx from the previous combustion cycle dilute the pre- chamber fuel-air mixture preventing rapid combustion in the pre-chamber. An air-controlled active TJI is presented in this paper in order to address these issues. By applying air to the pre-chamber at a sufficient pressure, residual gases are exhausted, and the air-fuel ratio is controlled within the pre-chamber, thereby improving the quality of combustion. This paper investigates the 3D-simulated combustion characteristics of a Direct Injected (DI-CNG) fuelled SI en- gine with a pre-chamber equipped with an air channel by using AVL FIRE software. Experiments and simulations were performed at the Worldwide Mapping Point (WWMP) at 1500 Revolutions Per Minute (RPM), 3.3 bar Indicated Mean Effective Pressure (IMEP), using only conventional spark plugs as the baseline. After validating simulation data, baseline engine conditions were set for all simulation scenarios at λ=1. Following that, the pre-chambers with and without an auxiliary fuel supply were simulated. In the simulated (DI-CNG) SI engine, active TJI was observed to perform better than passive TJI and spark plug. In conclusion, the active pre-chamber with an air channel demon-strated an improved thermal efficiency (ηth) over other counterparts and conventional spark ignition systems.

Keywords: turbulent jet ignition, active air control turbulent jet ignition, pre-chamber ignition system, active and passive pre-chamber, thermal efficiency, methane combustion, internal combustion engine combustion emissions

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3491 In-Silico Evaluation and Antihyperglycemic Potential of Leucas Cephalotes

Authors: Anjali Verma, Mahesh Pal, Veena Pande, Dalip Kumar Upreti

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The present study is carried out to explore the anti-hyperglycemic activity of Leucas cephalotes plant parts. A fruit, leaves, stems, and roots part of the Leucas cephalotes has been extracted in ethanol and have been evaluated for anti-hyperglycemic activity. The present study indicated that, ethanolic extract of fruit and leaves have shown significant α- amylase inhibitory activity with IC50 value of 92.86 ± 0.89 μg/mL and 98.09 ± 0.69 μg/mL respectively. Two known compounds β-sitosterol and lupeol were isolated from ethanolic extract of L. cephalotes leaves and were subjected to anti-hyperglycemic activity. Lupeol shows the best activity with IC50 55.73 ± 0.47 μg/mL and the results were verified by docking study of these compounds with mammalian α-amylase was carried out on its active site. It was concluded from the study that β-sitosterol and lupeol form one H-bond interactions with the active site residues either Asp212 or Thr21. The estimated free energy binding of β-sitosterol was found to be -9.47 kcal mol-1 with an estimated inhibition constant (Ki) of 558.94 nmol whereas the estimated free energy binding of lupeol was -11.73 kcal mol-1 with an estimated inhibition constant (Ki) of 476.71pmmol. The present study clearly showed that lupeol is more potent in comparison to β-sitosterol. The study indicates that L. cephalotes have significant potential to inhibit α-amylase enzyme.

Keywords: alpha-amylase, beta-sitosterol, hyperglycemia, lupeol

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3490 Cross-Sectional Analysis of Partner Support and Contraceptive Use in Adolescent Females

Authors: Ketan Tamirisa, Kathleen P. Tebb

Abstract:

In the U.S., annually, there are over 1 million pregnancies in teenagers and most (85%) are unintended. The need for proactive prevention measures is imperative to support adolescents with their pregnancy prevention and family planning goals. To date, there is limited research examining the extent to which support from a sexual partner(s) influences contraceptive use. To address this gap, this study assessed the relationship between sexually active adolescents, sex-assigned birth as female, and their perceived support from their sexual partner(s) about their contraceptive use in the last three months. Baseline data from sexually active adolescent females, between 13-19 years who were not currently using a long-acting contraceptive device, were recruited from 32 school-based health centers (SBHCs) in seven states in the U.S. as part of a larger study to evaluate Health-E You/ Salud iTuTM, a web-based contraceptive decision support tool. Fisher’s exact test assessed the cross-sectional association between perceived sexual partner support of contraceptive use in the past three months (felt no support, felt little support, and felt a lot of support), and current use of non-barrier contraception. A total of 91 sexually active adolescent females were eligible and completed the baseline survey. The mean age was 16.7 and nearly half (49.3%) were Hispanic/Latina. Most (85.9%) indicated it was very important to avoid becoming pregnant. A total of 60 participants (65.9%) reported use of non-barrier contraception. Of these, most used birth control pills (n=26), followed by Depo-Provera injection (n=12), patch (n=1), and ring (n=1). Most of the participants (80.2%) indicated that they perceived a lot of support from their partners and 19.8% reported no or little support. Among those reporting a lot of support, 69.9% (51/73) reported current use of non-barrier contraception compared to 50% (9/18) who felt no/little support and reported contraceptive use. This difference approached but did not reach statistical significance (p=0.096). Results from this preliminary data indicate that many adolescents who are coming in for care at SBHCs are at risk of unintended pregnancy. Many participants also reported a lot of support from their sexual partner(s) to use contraception. While the associations only approached significance, this is likely due to the small sample size. This and future research can better understand this association to inform interventions aimed at sexual partners to strengthen education and social support, increase healthcare accessibility, and ultimately reduce rates of unintended pregnancy.

Keywords: adolescents, contraception, pregnancy, SBHCs, sexual partners

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3489 Emerging Technologies for Learning: In Need of a Pro-Active Educational Strategy

Authors: Pieter De Vries, Renate Klaassen, Maria Ioannides

Abstract:

This paper is about an explorative research into the use of emerging technologies for teaching and learning in higher engineering education. The assumption is that these technologies and applications, which are not yet widely adopted, will help to improve education and as such actively work on the ability to better deal with the mismatch of skills bothering our industries. Technologies such as 3D printing, the Internet of Things, Virtual Reality, and others, are in a dynamic state of development which makes it difficult to grasp the value for education. Also, the instruments in current educational research seem not appropriate to assess the value of such technologies. This explorative research aims to foster an approach to better deal with this new complexity. The need to find out is urgent, because these technologies will be dominantly present in the near future in all aspects of life, including education. The methodology used in this research comprised an inventory of emerging technologies and tools that potentially give way to innovation and are used or about to be used in technical universities. The inventory was based on both a literature review and a review of reports and web resources like blogs and others and included a series of interviews with stakeholders in engineering education and at representative industries. In addition, a number of small experiments were executed with the aim to analyze the requirements for the use of in this case Virtual Reality and the Internet of Things to better understanding the opportunities and limitations in the day-today learning environment. The major findings indicate that it is rather difficult to decide about the value of these technologies for education due to the dynamic state of change and therefor unpredictability and the lack of a coherent policy at the institutions. Most decisions are being made by teachers on an individual basis, who in their micro-environment are not equipped to select, test and ultimately decide about the use of these technologies. Most experiences are being made in the industry knowing that the skills to handle these technologies are in high demand. The industry though is worried about the inclination and the capability of education to help bridge the skills gap related to the emergence of new technologies. Due to the complexity, the diversity, the speed of development and the decay, education is challenged to develop an approach that can make these technologies work in an integrated fashion. For education to fully profit from the opportunities, these technologies offer it is eminent to develop a pro-active strategy and a sustainable approach to frame the emerging technologies development.

Keywords: emerging technologies, internet of things, pro-active strategy, virtual reality

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3488 Assessing the Effects of Entrepreneurship Education and Moderating Variables on Venture Creation Intention of Undergraduate Students in Ghana

Authors: Daniel K. Gameti

Abstract:

The paper explored the effects of active and passive entrepreneurship education methods on the venture creation intention of undergraduate students in Ghana. The study also examined the moderating effect of gender and negative personal characteristics (risk tolerance, stress tolerance and fear of failure) on students’ venture creation intention. Deductive approach was used in collecting quantitative data from 555 business students from one public university and one private university through self-administered questionnaires. Descriptive statistic was used to determine the dominant method of entrepreneurship education used in Ghana. Further, structural equation model was used to test four hypotheses. The results of the study show that the dominant method of education used in Ghana was lectures and the least method used was field trip. The study further revealed that passive methods of education are less effective compared to active methods which were statistically significant in venture creation intention among students. There was also statistical difference between male and female students’ venture creation intention but stronger among male students and finally, the only personal characteristics that influence students’ intention was stress tolerance because risk tolerance and fear of failure were statistically insignificant.

Keywords: entrepreneurship education, Ghana, moderating variables, venture creation intention, undergraduate students

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3487 Effect of Probiotics and Vitamin B on Plasma Interferon-Gamma and Interleukin-6 Levels in Active Pulmonary Tuberculosis

Authors: Yulistiani Yulistiani, Zamrotul Izzah, Lintang Bismantara, Wenny Putri Nilamsari, Arif Bachtiar, Budi Suprapti

Abstract:

Interferon-gamma (IFN-γ) and interleukin-6 (IL-6) are pro-inflammatory cytokines, which have the protective immune response against Tuberculosis (TB). Indeed, pro-inflammatory cytokines Mycobacterium tuberculosis antigen-specific CD4+ and CD8+ T cells and NK cells increase the level of production of IFN-γ, a cytokine critical for augmenting the microbicidal activity of phagocytes. On the other hand, M. tuberculosis reduces the effects of IFN-γ by inhibiting the transcription of IFN-γ- responsive genes and by inducing the secretion of IL-6, which inhibits IFN-γ signaling. Probiotics Lactobacillus sp. and Bifidobacterium sp. were known to increase IFN-γ production in vivo, while vitamin B1, B6, and B12 worked on macrophages and releasing cytokines. Therefore, the present study was to evaluate the effect of probiotics and vitamin B supplement on changes of plasma cytokine levels in active pulmonary TB. From October to November 2016, twelve M. tuberculosis-infected patients starting anti-TB drugs were recruited, then divided into two groups. Seven patients were given a combination of probiotics and vitamin B, while five patients were in the control group. Plasma IFN-γ and IL-6 levels were measured by the ELISA kit before and a month after treatment. IFN-γ levels raised in four patients receiving the supplement (P = 0.743), while IL-6 increased in three patients in this group until day 30 of treatment (P = 0.298). Taken together, these results show the promising effect of probiotics and vitamin B on stimulation of IFN-γ and IL-6 production during intensive therapy of TB.

Keywords: interferon-gamma, interleukin-6, probiotic, tuberculosis

Procedia PDF Downloads 346
3486 Highly Selective Conversion of CO2 to CO on Cu Nanoparticles

Authors: Rauf Razzaq, Kaiwu Dong, Muhammad Sharif, Ralf Jackstell, Matthias Beller

Abstract:

Carbon dioxide (CO2), a key greenhouse gas produced from both anthropogenic and natural sources, has been recently considered to be an important C1 building-block for the synthesis of many industrial fuels and chemicals. Catalytic hydrogenation of CO2 using a heterogeneous system is regarded as an efficient process for CO2 valorization. In this regard CO2 reduction to CO via the reverse water gas shift reaction (RWGSR) has attracted much attention as a viable process for large scale commercial CO2 utilization. This process can generate syn-gas (CO+H2) which can provide an alternative route to direct CO2 conversion to methanol and/or liquid HCs from FT reaction. Herein, we report a highly active and selective silica supported copper catalyst with efficient CO2 reduction to CO in a slurry-bed batch autoclave reactor. The reactions were carried out at 200°C and 60 bar initial pressure with CO2/H2 ratio of 1:3 with varying temperature, pressure and fed-gas ratio. The gaseous phase products were analyzed using FID while the liquid products were analyzed by using FID detectors. It was found that Cu/SiO2 catalyst prepared using novel ammonia precipitation-urea gelation method achieved 26% CO2 conversion with a CO and methanol selectivity of 98 and 2% respectively. The high catalytic activity could be attributed to its strong metal-support interaction with highly dispersed and stabilized Cu+ species active for RWGSR. So, it can be concluded that reduction of CO2 to CO via RWGSR could address the problem of using CO2 gas in C1 chemistry.

Keywords: CO2 reduction, methanol, slurry reactor, synthesis gas

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3485 The Effects of Highly Active Antiretroviral Therapy (HAART) on the Expression of Muc1 and P65 in a Cervical Cancer Cell Line, HCS-2

Authors: K. R. Thabethe, G. A. Adefolaju, M. J. Hosie

Abstract:

Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24 hour treatment of a cervical cancer cell line, HCS-2, with drugs which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one way ANOVA followed by a Tukey Kramer Post Hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death, therefore the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.

Keywords: cervical cancer, haart, MUC1, P65

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3484 Computer Based Identification of Possible Molecular Targets for Induction of Drug Resistance Reversion in Multidrug Resistant Mycobacterium Tuberculosis

Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

Abstract:

Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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3483 Development of Heating Elements Based on Fe₂O₃ Reduction Products by Waste Active Sludge

Authors: Abigail Parra Parra, Jorge L. Morelos Hernandez, Pedro A. Marquez Agilar, Marina Vlasova, Jesus Colin De La Cruz

Abstract:

Carbothermal reduction of metal oxides is widely used both in metallurgical processes and in the production of oxygen-free refractory ceramics. As a rule, crushed coke and graphite are used as a reducing agent. The products of carbonization of organic compounds are among the innovative reducing agents. The aim of this work was to study the process of reduction of iron oxide (hematite) down to iron by waste active sludge (WAS) carbonization products. WAS was chosen due to the accumulation of a large amount of this type of waste, soil pollution, and the relevance of the development of technologies for its disposal. The studies have shown that the temperature treatment of mixtures WAS-Fe₂O₃ in the temperature range 900-1000 ºC for 1-5 hours under oxygen deficiency is described by the following scheme: WAS + Fe₂O₃→ C,CO + Fe₂O₃→ C + FexO → Fe (amorphous and crystalline). During the heat treatment of the mixtures, strong samples are formed. The study of the electrical conductive properties of such samples showed that, depending on the ratio of the components in the initial mixtures, it is possible to change the values of electrical resistivity from 5.6 Ω‧m to 151.6 Ω‧m When a current is passed through the samples, they are heated from 240 to 378ºC. Thus, based on WAS-Fe₂O₃ mixtures, heating elements can be created that can be used to heat ceramics and concrete.

Keywords: Fe₂O₃, reduction, waste activate sludge, electroconductivity

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3482 Synthesis, Antibacterial Activities, and Synergistic Effects of Novel Juglone and Naphthazarin Derivatives Against Clinical Methicillin-Resistant Staphylococcus aureus Strains

Authors: Zohra Benfodda, Valentin Duvauchelle, Chaimae Majdi, David Bénimélis, Catherine Dunyach-Remy, Patrick Meffre

Abstract:

New antibiotics are necessary to treat microbial pathogens, especially ESKAPE pathogens that are becoming increasingly resistant to available treatment. Despite the medical need, the number of newly approved drugs continues to decline. The majority of antibiotics under clinical development are natural products or derivatives thereof. 43 juglone/naphthazarin derivatives were synthesized using Minisci-type direct C–H alkylation and evaluated for their antibacterial properties against various clinical and reference Gram-positive MSSA, clinical Gram-positive MRSA. Different compounds of the synthesized series showed promising activity against clinical and reference MSSA (MIC: 1–8 μg/ml) and good efficacy against clinical MRSA (MIC: 2–8 μg/ml) strains. The synergistic effects of active compounds were evaluated with reference antibiotics (vancomycin and cloxacillin), and it was found that the antibiotic combination with those active compounds efficiently enhanced the antimicrobial activity and consequently the MIC values of reference antibiotics were lowered up to 1/16th of the original MIC. These synthesized compounds did not present hemolytic activity on sheep red blood cells. In addition to the in silico prediction of ADME profile parameter which is promising and encouraging for further development.

Keywords: juglone, naphthazarin, antibacterial, clinical MRSA, synergistic studies, MIC determination

Procedia PDF Downloads 124
3481 Investigation of Wind Farm Interaction with Ethiopian Electric Power’s Grid: A Case Study at Ashegoda Wind Farm

Authors: Fikremariam Beyene, Getachew Bekele

Abstract:

Ethiopia is currently on the move with various projects to raise the amount of power generated in the country. The progress observed in recent years indicates this fact clearly and indisputably. The rural electrification program, the modernization of the power transmission system, the development of wind farm is some of the main accomplishments worth mentioning. As it is well known, currently, wind power is globally embraced as one of the most important sources of energy mainly for its environmentally friendly characteristics, and also that once it is installed, it is a source available free of charge. However, integration of wind power plant with an existing network has many challenges that need to be given serious attention. In Ethiopia, a number of wind farms are either installed or are under construction. A series of wind farm is planned to be installed in the near future. Ashegoda Wind farm (13.2°, 39.6°), which is the subject of this study, is the first large scale wind farm under construction with the capacity of 120 MW. The first phase of 120 MW (30 MW) has been completed and is expected to be connected to the grid soon. This paper is concerned with the investigation of the wind farm interaction with the national grid under transient operating condition. The main concern is the fault ride through (FRT) capability of the system when the grid voltage drops to exceedingly low values because of short circuit fault and also the active and reactive power behavior of wind turbines after the fault is cleared. On the wind turbine side, a detailed dynamic modelling of variable speed wind turbine of a 1 MW capacity running with a squirrel cage induction generator and full-scale power electronics converters is done and analyzed using simulation software DIgSILENT PowerFactory. On the Ethiopian electric power corporation side, after having collected sufficient data for the analysis, the grid network is modeled. In the model, a fault ride-through (FRT) capability of the plant is studied by applying 3-phase short circuit on the grid terminal near the wind farm. The results show that the Ashegoda wind farm can ride from voltage deep within a short time and the active and reactive power performance of the wind farm is also promising.

Keywords: squirrel cage induction generator, active and reactive power, DIgSILENT PowerFactory, fault ride-through capability, 3-phase short circuit

Procedia PDF Downloads 171
3480 Preparation of n-type Bi2Te3 Films by Electrophoretic Deposition

Authors: Tahereh Talebi, Reza Ghomashchi, Pejman Talemi, Sima Aminorroaya

Abstract:

A high quality crack-free film of Bi2Te3 material has been deposited for the first time using electrophoretic deposition (EPD) and microstructures of various films have been investigated. One of the most important thermoelectric (TE) applications is Bi2Te3 to manufacture TE generators (TEG) which can convert waste heat into electricity targeting the global warming issue. However, the high cost of the manufacturing process of TEGs keeps them expensive and out of reach for commercialization. Therefore, utilizing EPD as a simple and cost-effective method will open new opportunities for TEG’s commercialization. This method has been recently used for advanced materials such as microelectronics and has attracted a lot of attention from both scientists and industry. In this study, the effect of media of suspensions has been investigated on the quality of the deposited films as well as their microstructure. In summary, finding an appropriate suspension is a critical step for a successful EPD process and has an important effect on both the film’s quality and its future properties.

Keywords: Bi2Te3, electrical conductivity, electrophoretic deposition, thermoelectric materials, thick films

Procedia PDF Downloads 252
3479 Profiling of the Cell-Cycle Related Genes in Response to Efavirenz, a Non-Nucleoside Reverse Transcriptase Inhibitor in Human Lung Cancer

Authors: Rahaba Marima, Clement Penny

Abstract:

The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

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3478 Targeting Apoptosis by Novel Adamantane Analogs as an Emerging Therapy for the Treatment of Hepatocellular Carcinoma Through EGFR, Bcl-2/BAX Cascade

Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

Abstract:

Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

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3477 Augmented ADRC for Trajectory Tracking of a Novel Hydraulic Spherical Motion Mechanism

Authors: Bin Bian, Liang Wang

Abstract:

A hydraulic spherical motion mechanism (HSMM) is proposed. Unlike traditional systems using serial or parallel mechanisms for multi-DOF rotations, the HSMM is capable of implementing continuous 2-DOF rotational motions in a single joint without the intermediate transmission mechanisms. It has some advantages of compact structure, low inertia and high stiffness. However, as HSMM is a nonlinear and multivariable system, it is very complicate to realize accuracy control. Therefore, an augmented active disturbance rejection controller (ADRC) is proposed in this paper. Compared with the traditional PD control method, three compensation items, i.e., dynamics compensation term, disturbance compensation term and nonlinear error elimination term, are added into the proposed algorithm to improve the control performance. The ADRC algorithm aims at offsetting the effects of external disturbance and realizing accurate control. Euler angles are applied to describe the orientation of rotor. Lagrange equations are utilized to establish the dynamic model of the HSMM. The stability of this algorithm is validated with detailed derivation. Simulation model is formulated in Matlab/Simulink. The results show that the proposed control algorithm has better competence of trajectory tracking in the presence of uncertainties.

Keywords: hydraulic spherical motion mechanism, dynamic model, active disturbance rejection control, trajectory tracking

Procedia PDF Downloads 103