Search results for: cell isolation
827 Design of Hybrid Auxetic Metamaterials for Enhanced Energy Absorption under Compression
Authors: Ercan Karadogan, Fatih Usta
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Auxetic materials have a negative Poisson’s ratio (NPR), which is not often found in nature. They are metamaterials that have potential applications in many engineering fields. Mechanical metamaterials are synthetically designed structures with unusual mechanical properties. These mechanical properties are dependent on the properties of the matrix structure. They have the following special characteristics, i.e., improved shear modulus, increased energy absorption, and intensive fracture toughness. Non-auxetic materials compress transversely when they are stretched. The system naturally is inclined to keep its density constant. The transversal compression increases the density to balance the loss in the longitudinal direction. This study proposes to improve the crushing performance of hybrid auxetic materials. The re-entrant honeycomb structure has been combined with a star honeycomb, an S-shaped unit cell, a double arrowhead, and a structurally hexagonal re-entrant honeycomb by 9 X 9 cells, i.e., the number of cells is 9 in the lateral direction and 9 in the vertical direction. The Finite Element (FE) and experimental methods have been used to determine the compression behavior of the developed hybrid auxetic structures. The FE models have been developed by using Abaqus software. The specimens made of polymer plastic materials have been 3D printed and subjected to compression loading. The results are compared in terms of specific energy absorption and strength. This paper describes the quasi-static crushing behavior of two types of hybrid lattice structures (auxetic + auxetic and auxetic + non-auxetic). The results show that the developed hybrid structures can be useful to control collapse mechanisms and present larger energy absorption compared to conventional re-entrant auxetic structures.Keywords: auxetic materials, compressive behavior, metamaterials, negative Poisson’s ratio
Procedia PDF Downloads 97826 LGR5 and Downstream Intracellular Signaling Proteins Play Critical Roles in the Cell Proliferation of Neuroblastoma, Meningioma and Pituitary Adenoma
Authors: Jin Hwan Cheong, Mina Hwang, Myung Hoon Han, Je Il Ryu, Young ha Oh, Seong Ho Koh, Wu Duck Won, Byung Jin Ha
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Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) has been reported to play critical roles in the proliferation of various cancer cells. However, the roles of LGR5 in brain tumors and the specific intracellular signaling proteins directly associated with it remain unknown. Expression of LGR5 was first measured in normal brain tissue, meningioma, and pituitary adenoma of humans. To identify the downstream signaling pathways of LGR5, siRNA-mediated knockdown of LGR5 was performed in SH-SY5Y neuroblastoma cells followed by proteomics analysis with 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE). In addition, the expression of LGR5-associated proteins was evaluated in LGR5-inꠓhibited neuroblastoma cells and in human normal brain, meningioma, and pituitary adenoma tissue. Proteomics analysis showed 12 protein spots were significantly different in expression level (more than two-fold change) and subsequently identified by peptide mass fingerprinting. A protein association network was constructed from the 12 identified proteins altered by LGR5 knockdown. Direct and indirect interactions were identified among the 12 proteins. HSP 90-beta was one of the proteins whose expression was altered by LGR5 knockdown. Likewise, we observed decreased expression of proteins in the hnRNP subfamily following LGR5 knockdown. In addition, we have for the first time identified significantly higher hnRNP family expression in meningioma and pituitary adenoma compared to normal brain tissue. Taken together, LGR5 and its downstream sigꠓnaling play critical roles in neuroblastoma and brain tumors such as meningioma and pituitary adenoma.Keywords: LGR5, neuroblastoma, meningioma, pituitary adenoma, hnRNP
Procedia PDF Downloads 56825 The Effect of Malaria Parasitaemia on Serum Reproductive Hormonal Levels of Asymptomatic HIV Subjects in Nauth Nnewi, South Eastern Nigeria
Authors: Ezeugwunne Ifeoma Priscilla, Charles Chinedum Onyenekwe, Joseph Eberendu Ahaneku, Rosemary Adanma Analike, Adesuwa Peace Eidangbe
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This study was designed to assess the effect of malaria parasitaemia on serum reproductive hormone levels of asymptomatic HIV adult subjects. A total of 271 participants aged between 17 and 58 ears were conveniently recruited. 135 asymptomatic HIV-infected subjects participated in the study; 67 of them had malaria parasitaemia. 136 HIV seropositive control subjects, 68 of them had malaria parasitaemia. Blood samples were collected from the participants for the determination of HIV status by immunoassay and immunochromatography. Enzyme-linked immunosorbent assay (ELISA) was used to assay for serum LH, FSH, Estrogen, testosterone, progesterone, prolactin, and PSA levels, CD4+T cell counts by Cyflow method, thick and thin films determination of malaria parasitaemia count and density by WHO. Student's t-tests and ANOVA were used to compare means. P<0.05 was considered statistically significant. The results showed significant differences in serum levels of LH, FSH, PSA, estrogen, progesterone, and testosterone amongst the groups at P<0.05, respectively. The serum levels of LH, FSH, and PSA were significantly higher in malaria-infected asymptomatic HIV subjects than in asymptomatic HIV subjects with malaria parasitaemia (P<0.05 in each case). Also, the serum levels of LH, FSH, PSA, estrogen, and progesterone were significantly higher in malaria-infected asymptomatic HIV subjects compared with malaria-infected HIV seronegative subjects (P<0.05, respectively). The mean MP counts and MP density were significantly higher in asymptomatic HIV subjects compared to HIV seronegative subjects (P<0.05, in each case). The mean serum levels of testosterone were significantly lower in both malaria-infected and malaria uninfected HIV seronegative subjects (P<0.05, in each case). In conclusion, Malaria and HIV co-infection might increase the burden of hypogonadism as well as primary testicular failure, hyperprogesteronaemia, elevated levels of estrogen, and PSA in adult males asymptomatic HIV subjects.Keywords: malaria parasitaemia, HIV, CD4, reproductive hormones
Procedia PDF Downloads 142824 Effect of Probiotic Feeding on Weight Gain, Blood Biochemical and Hematological Indices of Crossbred Dairy Goat Kids
Authors: Claire B. Salvedia, Enrico P. Supangco, Francisco B. Eligado, Renato Sa Vega, Antonio A. Rayos
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The study was conducted to evaluate the effect of probiotic feeding on weight gain, blood biochemical and hematological indices of crossbred dairy goat kids. Sixteen (16) crossbred Anglo-Nubian x Saanen dairy goat kids, 3 to 4 months old, ranging from 19 to 23kg were randomly assigned into four treatments fed with 5x109 cfu/ml probiotic supplements; Treatment 1 – control; Treatment 2 – lactic acid bacteria (L. plantarum BS and P. acidilactici 3G3); treatment 3 – S. cerevisiae 2030; Treatment 4 – multi-strain probiotics (L. plantarum BS, P. acidilactici 3G3, and S.cerevisiae 2030). Feed ration provided daily for each of the experimental animals were composed of 1kg mixed concentrate feed ((Leucaena leucocephala dried leaves and pollard), and 4 kg fresh Pennisetum purpureum and Gliciridia sepium leaves (50:50). The experimental feeding trial lasted for 9 weeks. Result revealed that treatments fed with probiotics had significantly (P≤0.05) higher weight gain compared to the control. Significant effect on plasma urea nitrogen (PUN) and triglyceride were noted during 30th and 60th day of probiotic feeding. White blood cell counts were significantly affected by probiotic feeding during the 60th day. Concentrations of glucose and cholesterol remained unchanged throughout the experimental period. The findings suggests, under the condition of the experiment, that live probiotic feeding could have a significant role in improving weight gain and metabolism of crossbred dairy goat kids.Keywords: probiotics, weight gain, blood biochemical indices, crossbred dairy goat kids
Procedia PDF Downloads 492823 Training Hearing Parents in SmiLE Therapy Supports the Maintenance and Generalisation of Deaf Children's Social Communication Skills
Authors: Martina Curtin, Rosalind Herman
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Background: Deaf children can experience difficulties with understanding how social interaction works, particularly when communicating with unfamiliar hearing people. Deaf children often struggle with integrating into a mainstream, hearing environments. These negative experiences can lead to social isolation, depression and other mental health difficulties later in life. smiLE Therapy (Schamroth, 2015) is a video-based social communication intervention that aims to teach deaf children skills to confidently communicate with unfamiliar hearing people. Although two previous studies have reported improvements in communication skills immediately post intervention, evidence for maintenance of gains or generalisation of skills (i.e., the transfer of newly learnt skills to untrained situations) has not to date been demonstrated. Parental involvement has been shown to support deaf children’s therapy outcomes. Therefore, this study added parent training to the therapy children received to investigate the benefits to generalisation of children’s skills. Parents were also invited to present their perspective on the training they received. Aims: (1) To assess pupils’ progress from pre- to post-intervention in trained and untrained tasks, (2) to investigate if training parents improved their (a) understanding of their child’s needs and (b) their skills in supporting their child appropriately in smiLE Therapy tasks, (3) to assess if parent training had an impact on the pupil’s ability to (a) maintain their skills in trained tasks post-therapy, and (b) generalise their skills in untrained, community tasks. Methods: This was a mixed-methods, repeated measures study. 31 deaf pupils (aged between 7 and 14) received an hour of smiLE Therapy per week, for 6 weeks. Communication skills were assessed pre-, post- and 3-months post-intervention using the Communication Skills Checklist. Parents were then invited to attend two training sessions and asked to bring a video of their child communicating in a shop or café. These videos were used to assess whether, after parent training, the child was able to generalise their skills to a new situation. Finally, parents attended a focus group to discuss the effectiveness of the therapy, particularly the wider impact, i.e., more child participation within the hearing community. Results: All children significantly improved their scores following smiLE therapy and maintained these skills to high level. Children generalised a high percentage of their newly learnt skills to an untrained situation. Parents reported improved understanding of their child’s needs, their child’s potential and in how to support them in real-life situations. Parents observed that their children were more confident and independent when carrying out communication tasks with unfamiliar hearing people. Parents realised they needed to ‘let go’ and embrace their child’s independence and provide more opportunities for them to participate in their community. Conclusions: This study adds to the evidence base on smiLE Therapy; it is an effective intervention that develops deaf children’s ability to interact competently with unfamiliar, hearing, communication partners. It also provides preliminary evidence of the benefits of parent training in helping children to generalise their skills to other situations. These findings will be of value to therapists wishing to develop deaf children’s communication skills beyond the therapy setting.Keywords: deaf children, generalisation, parent involvement, social communication
Procedia PDF Downloads 139822 The Prodomain-Bound Form of Bone Morphogenetic Protein 10 is Biologically Active on Endothelial Cells
Authors: Austin Jiang, Richard M. Salmon, Nicholas W. Morrell, Wei Li
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BMP10 is highly expressed in the developing heart and plays essential roles in cardiogenesis. BMP10 deletion in mice results in embryonic lethality due to impaired cardiac development. In adults, BMP10 expression is restricted to the right atrium, though ventricular hypertrophy is accompanied by increased BMP10 expression in a rat hypertension model. However, reports of BMP10 activity in the circulation are inconclusive. In particular it is not known whether in vivo secreted BMP10 is active or whether additional factors are required to achieve its bioactivity. It has been shown that high-affinity binding of the BMP10 prodomain to the mature ligand inhibits BMP10 signaling activity in C2C12 cells, and it was proposed that prodomain-bound BMP10 (pBMP10) complex is latent. In this study, we demonstrated that the BMP10 prodomain did not inhibit BMP10 signaling activity in multiple endothelial cells, and that recombinant human pBMP10 complex, expressed in mammalian cells and purified under native conditions, was fully active. In addition, both BMP10 in human plasma and BMP10 secreted from the mouse right atrium were fully active. Finally, we confirmed that active BMP10 secreted from mouse right atrium was in the prodomain-bound form. Our data suggest that circulating BMP10 in adults is fully active and that the reported vascular quiescence function of BMP10 in vivo is due to the direct activity of pBMP10 and does not require an additional activation step. Moreover, being an active ligand, recombinant pBMP10 may have therapeutic potential as an endothelial-selective BMP ligand, in conditions characterized by loss of BMP9/10 signaling.Keywords: bone morphogenetic protein 10 (BMP10), endothelial cell, signal transduction, transforming growth factor beta (TGF-B)
Procedia PDF Downloads 273821 External Program Evaluation: Impacts and Changes on Government-Assisted Refugee Mothers
Authors: Akiko Ohta, Masahiro Minami, Yusra Qadir, Jennifer York
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The Home Instruction for Parents of Preschool Youngsters (HIPPY) is a home instruction program for mothers of children 3 to 5 years old. Using role-play as a method of teaching, the participating mothers work with their home visitors and learn how to deliver the HIPPY curriculum to their children. Applying HIPPY, Reviving Hope and Home for High-risk Refugee Mothers Program (RHH) was created to provide more personalized peer support and to respond to ongoing settlement challenges for isolated and vulnerable Government Assisted Refugee (GAR) mothers. GARs often have greater needs and vulnerabilities than other refugee groups. While the support is available, they often face various challenges and barriers in starting their new lives in Canada, such as inadequate housing, low first-language literacy levels, low competency in English or French, and social isolation. The pilot project was operated by Mothers Matter Centre (MMC) from January 2019 to March 2021 in partnership with the Immigrant Services Society of BC (ISSofBC). The formative evaluation was conducted by a research team at Simon Fraser University. In order to provide more suitable support for GAR mothers, RHH intended to offer more flexibility in HIPPY delivery, supported by a home visitor, to meet the need of refugee mothers facing various conditions and challenges; to have a pool of financial resources to be used for the RHH families when necessitated during the program period; to have another designated staff member, called a community navigator, assigned to facilitate the support system for the RHH families in their settlement; to have a portable device available for each RHH mother to navigate settlement support resources; and to provide other variations of the HIPPY curriculum as an option for the RHH mothers, including a curriculum targeting pre-HIPPY age children. Reflections on each program component was collected from RHH mothers and staff members of MMC and ISSofBC, including frontline workers and management staff, through individual interviews and focus group discussions. Each of the RHH program components was analyzed and evaluated by applying Moore’s four domains framework to identify key information and generate new knowledge (data). To capture RHH mothers’ program experience more in depth based on their own reflections, the photovoice method was used. Some photos taken by the mothers will be shared to illustrate their RHH experience as part of their life stories. Over the period of the program, this evaluation observed how RHH mothers became more confident in various domains, such as communicating with others, taking public transportations alone, and teaching their own child(ren). One of the major factors behind the success was their home visitors’ flexibility and creativity to create a more meaningful and tailored approach for each mother, depending on her background and personal situation. The role of the community navigator was tested out and improved during the program period. The community navigators took the key role to assess the needs of the RHH families and connect them with community resources. Both the home visitors and community navigators were immigrant mothers themselves and owing to their dedicated care for the RHH mothers; they were able to gain trust and work closely and efficiently with RHH mothers.Keywords: refugee mothers, settlement support, program evaluation, Canada
Procedia PDF Downloads 171820 Review of Strategies for Hybrid Energy Storage Management System in Electric Vehicle Application
Authors: Kayode A. Olaniyi, Adeola A. Ogunleye, Tola M. Osifeko
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Electric Vehicles (EV) appear to be gaining increasing patronage as a feasible alternative to Internal Combustion Engine Vehicles (ICEVs) for having low emission and high operation efficiency. The EV energy storage systems are required to handle high energy and power density capacity constrained by limited space, operating temperature, weight and cost. The choice of strategies for energy storage evaluation, monitoring and control remains a challenging task. This paper presents review of various energy storage technologies and recent researches in battery evaluation techniques used in EV applications. It also underscores strategies for the hybrid energy storage management and control schemes for the improvement of EV stability and reliability. The study reveals that despite the advances recorded in battery technologies there is still no cell which possess both the optimum power and energy densities among other requirements, for EV application. However combination of two or more energy storages as hybrid and allowing the advantageous attributes from each device to be utilized is a promising solution. The review also reveals that State-of-Charge (SoC) is the most crucial method for battery estimation. The conventional method of SoC measurement is however questioned in the literature and adaptive algorithms that include all model of disturbances are being proposed. The review further suggests that heuristic-based approach is commonly adopted in the development of strategies for hybrid energy storage system management. The alternative approach which is optimization-based is found to be more accurate but is memory and computational intensive and as such not recommended in most real-time applications.Keywords: battery state estimation, hybrid electric vehicle, hybrid energy storage, state of charge, state of health
Procedia PDF Downloads 242819 Anti-Aging Effects of Retinol and Alpha Hydroxy Acid on Elastin Fibers of Artificially Photo-Aged Human Dermal Fibroblast Cell Lines
Authors: Mohammed Jarrar, Shalini Behl, Nadia Shaheen, Abeer Fatima, Reem Nasab
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Skin aging is a slow multifactorial process influenced by both internal as well as external factors. Ultra-violet radiations (UV), diet, smoking and personal habits are the most common environmental factors that affect skin aging. Fat contents and fibrous proteins as collagen and elastin are core internal structural components. The direct influence of UV on elastin integrity and health is crucial on aging of skin by time. The deposition of abnormal elastic material is a major marker in a photo-aged skin. Searching for compounds that may protect against cutaneous photo-damage is highly valued. Retinoids and Alpha Hydroxy Acids protective and or repairing effects of UV have been endorsed by some researchers. For consolidating a better understanding of anti and protective effects of such anti-aging agents, we evaluated the combinatory effects of various dosages of lactic acid and retinol on the dermal fibroblasts elastin levels exposed to UV. The UV exposed cells showed significant reduction in the elastin levels. A combination of drugs with a higher concentration of lactic acid (30-35 mM) and a lower concentration of retinol (10-15mg/mL) showed to work better in enhancing elastin concentration in UV exposed cells. We assume this enhancement could be the result of increased tropo-elastin gene expression stimulated by retinol and lactic acid probably repaired the UV irradiated damage by enhancing the amount and integrity of the elastin fibers.Keywords: alpha hydroxy acid, elastin, retinol, ultraviolet radiations
Procedia PDF Downloads 342818 Mobile Network Users Amidst Ultra-Dense Networks in 5G Using an Improved Coordinated Multipoint (CoMP) Technology
Authors: Johnson O. Adeogo, Ayodele S. Oluwole, O. Akinsanmi, Olawale J. Olaluyi
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In this 5G network, very high traffic density in densely populated areas, most especially in densely populated areas, is one of the key requirements. Radiation reduction becomes one of the major concerns to secure the future life of mobile network users in ultra-dense network areas using an improved coordinated multipoint technology. Coordinated Multi-Point (CoMP) is based on transmission and/or reception at multiple separated points with improved coordination among them to actively manage the interference for the users. Small cells have two major objectives: one, they provide good coverage and/or performance. Network users can maintain a good quality signal network by directly connecting to the cell. Two is using CoMP, which involves the use of multiple base stations (MBS) to cooperate by transmitting and/or receiving at the same time in order to reduce the possibility of electromagnetic radiation increase. Therefore, the influence of the screen guard with rubber condom on the mobile transceivers as one major piece of equipment radiating electromagnetic radiation was investigated by mobile network users amidst ultra-dense networks in 5g. The results were compared with the same mobile transceivers without screen guards and rubber condoms under the same network conditions. The 5 cm distance from the mobile transceivers was measured with the help of a ruler, and the intensity of Radio Frequency (RF) radiation was measured using an RF meter. The results show that the intensity of radiation from various mobile transceivers without screen guides and condoms was higher than the mobile transceivers with screen guides and condoms when call conversation was on at both ends.Keywords: ultra-dense networks, mobile network users, 5g, coordinated multi-point.
Procedia PDF Downloads 103817 Affordable Aerodynamic Balance for Instrumentation in a Wind Tunnel Using Arduino
Authors: Pedro Ferreira, Alexandre Frugoli, Pedro Frugoli, Lucio Leonardo, Thais Cavalheri
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The teaching of fluid mechanics in engineering courses is, in general, a source of great difficulties for learning. The possibility of the use of experiments with didactic wind tunnels can facilitate the education of future professionals. The objective of this proposal is the development of a low-cost aerodynamic balance to be used in a didactic wind tunnel. The set is comprised of an Arduino microcontroller, programmed by an open source software, linked to load cells built by students from another project. The didactic wind tunnel is 5,0m long and the test area is 90,0 cm x 90,0 cm x 150,0 cm. The Weq® electric motor, model W-22 of 9,2 HP, moves a fan with nine blades, each blade 32,0 cm long. The Weq® frequency inverter, model WEGCFW 08 (Vector Inverter) is responsible for wind speed control and also for the motor inversion of the rotational direction. A flat-convex profile prototype of airfoil was tested by measuring the drag and lift forces for certain attack angles; the air flux conditions remained constant, monitored by a Pitot tube connected to a EXTECH® Instruments digital pressure differential manometer Model HD755. The results indicate a good agreement with the theory. The choice of all of the components of this proposal resulted in a low-cost product providing a high level of specific knowledge of mechanics of fluids, which may be a good alternative to teaching in countries with scarce educational resources. The system also allows the expansion to measure other parameters like fluid velocity, temperature, pressure as well as the possibility of automation of other functions.Keywords: aerodynamic balance, wind tunnel, strain gauge, load cell, Arduino, low-cost education
Procedia PDF Downloads 444816 The Methanotrophic Activity in a Landfill Bio-Cover through a Subzero Winter
Authors: Parvin Berenjkar, Qiuyan Yuan, Richard Sparling, Stan Lozecznik
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Landfills highly contribute to anthropological global warming through CH₄ emissions. Landfills are usually capped by a conventional soil cover to control the migration of gases. Methane is consumed by CH₄-oxidizing microorganisms known as methanotrophs that naturally exist in the landfill soil cover. The growth of methanotrophs can be optimized in a bio-cover that typically consists of a gas distribution layer (GDL) to homogenize landfill gas fluxes and an overlying oxidation layer composed of suitable materials that support methanotrophic populations. Materials such as mature yard waste composts can provide an inexpensive and favourable porous support for the growth and activity of methanotrophs. In areas with seasonal cold climates, it is valuable to know if methanotrophs in a bio-cover can survive in winter until the next spring, and how deep they are active in the bio-cover to mitigate CH₄. In this study, a pilot bio-cover was constructed in a closed landfill cell in Winnipeg that has a very cold climate in Canada. The bio-cover has a surface area of 2.5 m x 3.5 m and 1.5 m of depth, filled with 50 cm of gravel as a GDL and 70 cm of biosolids compost amended with yard and leaf waste compost. The observed in situ potential of methanotrophs for CH₄ oxidation was investigated at a specific period of time from December 2016 to April 2017 as well as November 2017 to April 2018, when the transition to surface frost and thawing happens in the bio-cover. Compost samples taken from different depths of the bio-cover were incubated in the laboratory under standardized conditions; an optimal air: methane atmosphere, at 22ºC, but at in situ moisture content. Results showed that the methanotrophs were alive oxidizing methane without a lag, indicating that there was the potential for methanotrophic activity at some depths of the bio-cover.Keywords: bio-cover, global warming, landfill, methanotrophic activity
Procedia PDF Downloads 121815 The Effect of Vitamin D Supplementation on Prostate Cancer: A Systematic Review and Meta-Analysis of Clinical Trials
Authors: Simin Shahvazi, Sepideh Soltani, Seyed Mehdi Ahmadi, Russell J. De Souza, Amin Salehi-Abargouei
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Background and Objectives: Vitamin D has received attention for its potential to disrupt cancer processes such as attenuating cell proliferation and exacerbating differentiation and apoptosis. However, whether there exists a role for vitamin D in the treatment of prostate cancer specifically remains controversial. We systematically review the literature to assess whether supplementation with vitamin D influences PSA response and overall survival in patients with prostate cancer. Methods: We searched PubMed, Scopus, ISI Web of Science and Google scholar from inception through up to 10 September 2017 for both before-and-after and randomized trials that evaluated the effect of vitamin D supplementation on the prostate specific antigen (PSA) response rate in participants with prostate cancer. The DerSimonian and Laird, inverse-weighted random-effects model was used to pool effect estimates from the studies. Heterogeneity and potential publication bias were evaluated. Subgroup analyses were also performed. Results: Twenty-two studies (16 before-after and 6 randomized controlled trials) were found and included in meta-analysis. The analysis on controlled clinical trials revealed that PSA change from baseline [weighted mean difference (WMD) = -1.66 ng/ml, 95%CI: -0.69, 0.36, P= 0.543)], PSA response (RR=1.18, 95%CI: 0.97, 1.45, P=0.104) and mortality rate (risk ratio (RR) = 1.05, 95% CI: 0.81-1.36; P=0.713) was not significantly different between vitamin D supplementation and placebo groups. Single arm trials revealed that vitamin D supplementation had had a modest effect on PSA response rate: 19% of those enrolled had at least a 50% reduction in PSA by the end of treatment (95% CI: 7% to 31%; p=0.002). Conclusion: We found that vitamin D modestly increases the PSA response rate in single arm studies. No effect on serum PSA levels, PSA response and mortality was seen in randomized controlled clinical trials. It does not seem patients with prostate cancer benefit from vitamin D supplementation.Keywords: mortality, prostatic neoplasms, PSA response, vitamin D
Procedia PDF Downloads 195814 Infused Mesenchymal Stem Cells Ameliorate Organs Morphology in Cerebral Malaria Infection
Authors: Reva Sharan Thakur, Mrinalini Tiwari, Jyoti das
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Cerebral malaria-associated over expression of pro-inflammatory cytokines and chemokines ultimately results in the up-regulation of adhesion molecules in the brain endothelium leading to sequestration of mature parasitized RBCs in the brain. The high-parasitic load subsequently results in increased mortality or development of neurological symptoms within a week of infection. Studies in the human and experimental cerebral malaria have implicated the breakdown of the integrity of blood-brain barrier during the lethal course of infection, cerebral dysfunction, and fatal organ pathologies that result in multi-organ failure. In the present study, using Plasmodium berghei Anka as a mouse model and in vitro conditions, we have investigated the effect of MSCs to attenuate cerebral malaria pathogenesis by diminishing the effect of inflammation altered organ morphology, reduced parasitemia, and increased survival of the mice. MSCs are also validated for their role in preventing BBB dysfunction and reducing malarial toxins. It was observed that administration of MSCs significantly reduced parasitemia and increased survival in Pb A infected mice. It was further demonstrated that MSCs play a significant role in reversing neurological complexities associated with cerebral malaria. Infusion of MSCs in infected mice decreased hemozoin deposition; oedema, and haemorrhagic lesions in vascular organs. MSCs administration also preserved the integrity of the blood-brain barrier and reduced neural inflammation. Taken together, our results demonstrate the potential of MSCs as an emerging anti-malarial candidate.Keywords: cerebral malaria, mesenchymal stem cells, erythropoesis, cell death
Procedia PDF Downloads 103813 Membrane Technologies for Obtaining Bioactive Fractions from Blood Main Protein: An Exploratory Study for Industrial Application
Authors: Fatima Arrutia, Francisco Amador Riera
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The meat industry generates large volumes of blood as a result of meat processing. Several industrial procedures have been implemented in order to treat this by-product, but are focused on the production of low-value products, and in many cases, blood is simply discarded as waste. Besides, in addition to economic interests, there is an environmental concern due to bloodborne pathogens and other chemical contaminants found in blood. Consequently, there is a dire need to find extensive uses for blood that can be both applicable to industrial scale and able to yield high value-added products. Blood has been recognized as an important source of protein. The main blood serum protein in mammals is serum albumin. One of the top trends in food market is functional foods. Among them, bioactive peptides can be obtained from protein sources by microbiological fermentation or enzymatic and chemical hydrolysis. Bioactive peptides are short amino acid sequences that can have a positive impact on health when administered. The main drawback for bioactive peptide production is the high cost of the isolation, purification and characterization techniques (such as chromatography and mass spectrometry) that make unaffordable the scale-up. On the other hand, membrane technologies are very suitable to apply to the industry because they offer a very easy scale-up and are low-cost technologies, compared to other traditional separation methods. In this work, the possibility of obtaining bioactive peptide fractions from serum albumin by means of a simple procedure of only 2 steps (hydrolysis and membrane filtration) was evaluated, as an exploratory study for possible industrial application. The methodology used in this work was, firstly, a tryptic hydrolysis of serum albumin in order to release the peptides from the protein. The protein was previously subjected to a thermal treatment in order to enhance the enzyme cleavage and thus the peptide yield. Then, the obtained hydrolysate was filtered through a nanofiltration/ultrafiltration flat rig at three different pH values with two different membrane materials, so as to compare membrane performance. The corresponding permeates were analyzed by liquid chromatography-tandem mass spectrometry technology in order to obtain the peptide sequences present in each permeate. Finally, different concentrations of every permeate were evaluated for their in vitro antihypertensive and antioxidant activities though ACE-inhibition and DPPH radical scavenging tests. The hydrolysis process with the previous thermal treatment allowed achieving a degree of hydrolysis of the 49.66% of the maximum possible. It was found that peptides were best transmitted to the permeate stream at pH values that corresponded to their isoelectric points. Best selectivity between peptide groups was achieved at basic pH values. Differences in peptide content were found between membranes and also between pH values for the same membrane. The antioxidant activity of all permeates was high compared with the control only for the highest dose. However, antihypertensive activity was best for intermediate concentrations, rather than higher or lower doses. Therefore, although differences between them, all permeates were promising regarding antihypertensive and antioxidant properties.Keywords: bioactive peptides, bovine serum albumin, hydrolysis, membrane filtration
Procedia PDF Downloads 200812 Electrochemical Growth and Properties of Cu2O Nanostructures
Authors: A. Azizi, S. Laidoudi, G. Schmerber, A. Dinia
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Cuprous oxide (Cu2O) is a well-known oxide semiconductor with a band gap of 2.1 eV and a natural p-type conductivity, which is an attractive material for device applications because of its abundant availability, non toxicity, and low production cost. It has a higher absorption coefficient in the visible region and the minority carrier diffusion length is also suitable for use as a solar cell absorber layer and it has been explored in junction with n type ZnO for photovoltaic applications. Cu2O nanostructures have been made by a variety of techniques; the electrodeposition method has emerged as one of the most promising processing routes as it is particularly provides advantages such as a low-cost, low temperature and a high level of purity in the products. In this work, Cu2O nanostructures prepared by electrodeposition from aqueous cupric sulfate solution with citric acid at 65°C onto a fluorine doped tin oxide (FTO) coated glass substrates were investigated. The effects of deposition potential on the electrochemical, surface morphology, structural and optical properties of Cu2O thin films were investigated. During cyclic voltammetry experiences, the potential interval where the electrodeposition of Cu2O is carried out was established. The Mott–Schottky (M-S) plot demonstrates that all the films are p-type semiconductors, the flat-band potential and the acceptor density for the Cu2O thin films are determined. AFM images reveal that the applied potential has a very significant influence on the surface morphology and size of the crystallites of thin Cu2O. The XRD measurements indicated that all the obtained films display a Cu2O cubic structure with a strong preferential orientation of the (111) direction. The optical transmission spectra in the UV-Visible domains revealed the highest transmission (75 %), and their calculated gap values increased from 1.93 to 2.24 eV, with increasing potentials.Keywords: Cu2O, electrodeposition, Mott–Schottky plot, nanostructure, optical properties, XRD
Procedia PDF Downloads 355811 Study of Structural Behavior and Proton Conductivity of Inorganic Gel Paste Electrolyte at Various Phosphorous to Silicon Ratio by Multiscale Modelling
Authors: P. Haldar, P. Ghosh, S. Ghoshdastidar, K. Kargupta
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In polymer electrolyte membrane fuel cells (PEMFC), the membrane electrode assembly (MEA) is consisting of two platinum coated carbon electrodes, sandwiched with one proton conducting phosphoric acid doped polymeric membrane. Due to low mechanical stability, flooding and fuel cell crossover, application of phosphoric acid in polymeric membrane is very critical. Phosphorous and silica based 3D inorganic gel gains the attention in the field of supercapacitors, fuel cells and metal hydrate batteries due to its thermally stable highly proton conductive behavior. Also as a large amount of water molecule and phosphoric acid can easily get trapped in Si-O-Si network cavities, it causes a prevention in the leaching out. In this study, we have performed molecular dynamics (MD) simulation and first principle calculations to understand the structural, electronics and electrochemical and morphological behavior of this inorganic gel at various P to Si ratios. We have used dipole-dipole interactions, H bonding, and van der Waals forces to study the main interactions between the molecules. A 'structure property-performance' mapping is initiated to determine optimum P to Si ratio for best proton conductivity. We have performed the MD simulations at various temperature to understand the temperature dependency on proton conductivity. The observed results will propose a model which fits well with experimental data and other literature values. We have also studied the mechanism behind proton conductivity. And finally we have proposed a structure for the gel paste with optimum P to Si ratio.Keywords: first principle calculation, molecular dynamics simulation, phosphorous and silica based 3D inorganic gel, polymer electrolyte membrane fuel cells, proton conductivity
Procedia PDF Downloads 129810 Reinforcement-Learning Based Handover Optimization for Cellular Unmanned Aerial Vehicles Connectivity
Authors: Mahmoud Almasri, Xavier Marjou, Fanny Parzysz
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The demand for services provided by Unmanned Aerial Vehicles (UAVs) is increasing pervasively across several sectors including potential public safety, economic, and delivery services. As the number of applications using UAVs grows rapidly, more and more powerful, quality of service, and power efficient computing units are necessary. Recently, cellular technology draws more attention to connectivity that can ensure reliable and flexible communications services for UAVs. In cellular technology, flying with a high speed and altitude is subject to several key challenges, such as frequent handovers (HOs), high interference levels, connectivity coverage holes, etc. Additional HOs may lead to “ping-pong” between the UAVs and the serving cells resulting in a decrease of the quality of service and energy consumption. In order to optimize the number of HOs, we develop in this paper a Q-learning-based algorithm. While existing works focus on adjusting the number of HOs in a static network topology, we take into account the impact of cells deployment for three different simulation scenarios (Rural, Semi-rural and Urban areas). We also consider the impact of the decision distance, where the drone has the choice to make a switching decision on the number of HOs. Our results show that a Q-learning-based algorithm allows to significantly reduce the average number of HOs compared to a baseline case where the drone always selects the cell with the highest received signal. Moreover, we also propose which hyper-parameters have the largest impact on the number of HOs in the three tested environments, i.e. Rural, Semi-rural, or Urban.Keywords: drones connectivity, reinforcement learning, handovers optimization, decision distance
Procedia PDF Downloads 108809 The Lifecycle of a Heritage Language: A Comparative Case Study of Volga German Descendants in North America
Authors: Ashleigh Dawn Moeller
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This is a comparative case study which examines the language attitudes and behaviors of descendants of Volga German immigrants in North America and how these attitudes combined with surrounding social conditions have caused their heritage language to develop differently within each community. Of particular interest for this study are the accounts of second- and third-generation descendants in Oregon, Kansas, and North Dakota regarding their parents’ and grandparents’ attitudes toward their language and how this correlates with the current sentiment as well as visibility of their heritage language and culture. This study discusses the point at which cultural identity could diverge from language identity and what elements play a role in this development, establishing the potential for environments (linguistic landscapes) which uphold their heritage yet have detached from the language itself. Emigrating from Germany in the 1700s, these families settled for over a hundred years along the Volga Region of Imperial Russia. Subsequently, many descendants of these settlers immigrated to the Americas in the 1800-1900s. Identifying neither as German nor Russian, they called themselves Wolgadeutche (Volga Germans). During their time in Russia, the German language was maintained relatively homogenously, yet the use and status of their heritage language diverged considerably upon settlement across the Americas. Data shows that specific conditions, such as community isolation, size, religion, location as well as language policy established prior to and following the Volga German immigration to North America have had a substantial impact on the maintenance of their heritage language—causing complete loss in some areas and peripheral use or even full rebirth in others. These past conditions combined with the family accounts correlate directly with the general attitudes and ideologies of the descendants toward their heritage language. Data also shows that in many locations, despite a strong presence of German within the linguistic landscape, minimal to no German is spoken nor understood; the attitude toward the language is indifferent while a staunch holding to the heritage is maintained and boasted. Data for this study was gathered from historical accounts, archived records and newspapers, and published biographies as well as from formal interviews with second- and third-generation descendants of Volga German immigrants conducted in Oregon and Kansas. Through the interviews, members of the community have shared and provided their family genealogies as well as biographies published by family members. These have helped to trace their relatives back to specific locations, thus allowing for comparisons within the same families residing in distinctly different areas of North America. This study is part of a larger ongoing project which researches the immigration of Volga and Black Sea Germans to North America and diachronically examines the over-arching sociological factors which have directly impacted the maintenance, loss, or rebirth of their heritage language. This project follows specific families who settled in areas of Colorado, Kansas, Nebraska, Illinois, Minnesota, North and South Dakota, Saskatchewan, and Manitoba, and who later had relatives move west to areas of Oregon and Washington State. Interviews for the larger project will continue into the following year.Keywords: heritage language, immigrant language, language change, language contact, linguistic landscape, Volga Germans, Wolgadeutsche
Procedia PDF Downloads 121808 Integrated Design of Froth Flotation Process in Sludge Oil Recovery Using Cavitation Nanobubbles for Increase the Efficiency and High Viscose Compatibility
Authors: Yolla Miranda, Marini Altyra, Karina Kalmapuspita Imas
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Oily sludge wastes always fill in upstream and downstream petroleum industry process. Sludge still contains oil that can use for energy storage. Recycling sludge is a method to handling it for reduce the toxicity and very probable to get the remaining oil around 20% from its volume. Froth flotation, a common method based on chemical unit for separate fine solid particles from an aqueous suspension. The basic composition of froth flotation is the capture of oil droplets or small solids by air bubbles in an aqueous slurry, followed by their levitation and collection in a froth layer. This method has been known as no intensive energy requirement and easy to apply. But the low efficiency and unable treat the high viscosity become the biggest problem in froth flotation unit. This study give the design to manage the high viscosity of sludge first and then entering the froth flotation including cavitation tube on it to change the bubbles into nano particles. The recovery in flotation starts with the collision and adhesion of hydrophobic particles to the air bubbles followed by transportation of the hydrophobic particle-bubble aggregate from the collection zone to the froth zone, drainage and enrichment of the froth, and finally by its overflow removal from the cell top. The effective particle separation by froth flotation relies on the efficient capture of hydrophobic particles by air bubbles in three steps. The important step is collision. Decreasing the bubble particles will increasing the collision effect. It cause the process more efficient. The pre-treatment, froth flotation, and cavitation tube integrated each other. The design shows the integrated unit and its process.Keywords: sludge oil recovery, froth flotation, cavitation tube, nanobubbles, high viscosity
Procedia PDF Downloads 378807 Cytotoxic, Antimicrobial and Antiviral Activities of Acovenoside A: A Cardenolide Isolated from an Egyptian Cultivar of Acokanthera spectabilis Leaves
Authors: Howaida I. Abd-Alla, Amal Z. Hassan, Maha Soltan, Atef G. Hanna, Mounir M. El-Safty
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Acokanthera oblongifolia (Apocynaceae) is used for treatment of several infection diseases and is a well-known cardiac glycoside-containing plant. The infusion of their leaves is gargled to treat tonsillitis and is used medicinally to treat snakebites. The total cardiac glycosides content in the leaves was determined by referring to gitoxigenin as a reference compound. Two triterpenes, lup-20(29)-en-3β-ol (1) and oleanolic acid (2); two cardenolides, acovenoside A (3) and acobioside A (4) were isolated from the ethyl acetate extract. Their structures were determined on the basis of spectral analysis. Major constituents isolated from this species were evaluated for cytotoxicity against normal lung cell line (Wi38) and antimicrobial activities against Gram-positive (two strains) and Gram-negative bacteria (four strains), yeast-like fungi (two strains) and fungi (five strains). The minimum inhibitory concentration (MIC) of the compounds was determined using broth microdilution method. Their viral inhibitory effects against avian influenza virus type A (AI-H5N1) and Newcastle disease virus (NDV) in specific pathogen free (SPF) embryonated chicken eggs (ECE), chicken embryo fibroblasts (CEF) and Vero cells were evaluated. The cardenolide (3) showed viral inhibitory effects against AI-H5N1 and NDV in SPF ECE. The two cardenolides isolated have shown potent cytotoxicity against Vero cells. Compound (3) showed potent anti-Gram-negative bacteria activity. These results suggested that acovenoside A might be promising for future antiviral and antimicrobial drug design.Keywords: Acokanthera, AI-H5N1, Cardenolides, NDV, SPF-ECE, VERO, Wi38 , Microbe
Procedia PDF Downloads 178806 Antiplasmodial Activity of Drimane Sesquiterpene Isolated from Warburgia salutaris
Authors: Mthokozisi Simelane
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Background: Malaria remains a life-threatening disease in tropical regions despite the advances in the treatment of this disease, it still remains a significant burden as some parasites have become resistant to the currently available drugs. This has created a necessity for the development of alternative, more efficient antimalarial drugs. Warburgia salutaris is a traditional medicinal plant used in malaria treatment by Zulu traditional healers. Materials and methods: The W. salutaris stem-bark was extracted with dichloromethane and the compound was isolated through column chromatography. The compound was identified and characterized by spectroscopic analysis (1H NMR, 13C NMR, IR and MS) and the structure was also confirmed by x-ray crystallography. The anti-plasmodial activity (in vitro) was studied on NF54 Plasmodium falciparum strain (CQS). Cytotoxicity was measured using the MTT assay on HEK239 and HEPG2 cell lines. Docking of Mukaadial acetate was conducted in AutoDock Vina. Structural modifications were conducted in UCSF Chimera and molecular interactions examined in LigPlot. Results: The compound, Mukaadial Acetate showed appreciable inhibition (IC50 0.44±0.10 µg/ml) of the parasite growth and cytotoxicity activity of 0.124±0.109 and 0.199±0.083 (µg/ml) on HEK293 and HEPG2 cells respectively. Molecular docking revealed that Mukaadial Acetate binds to the purine, pyrophosphate and ribose binding sites of the PfHGXPRT with an optimum binding conformation and forms hydrogen bond, steric and hydrophobic interactions with the residues inhabiting the respective binding sites. Conclusion: It is apparent that W. salutaris contains components (including Mukaadial Acetate) that exhibit antimalarial activity. This study scientifically validates the use of this plant in folk medicine.Keywords: plasmodium falciparum, molecular docking, antimalarial activity, PfHGXPRT, Warburgia salutaris, mukaadial acetate
Procedia PDF Downloads 197805 Receptor-Independent Effects of Endocannabinoid Anandamide on Contractility and Electrophysiological Properties of Rat Ventricular Myocytes
Authors: Lina T. Al Kury, Oleg I. Voitychuk, Ramiz M. Ali, Sehamuddin Galadari, Keun-Hang Susan Yang, Frank Christopher Howarth, Yaroslav M. Shuba, Murat Oz
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A role for anandamide (N-arachidonoyl ethanolamide; AEA), a major endocannabinoid, in the cardiovascular system in various pathological conditions has been reported in earlier studies. In the present work, we have hypothesized that the antiarrhythmic effects reported for AEA are due to its negative inotropic effect and altered action potential (AP) characteristics. Therefore, we tested the effects of AEA on contractility and electrophysiological properties of rat ventricular myocytes. Video edge detection was used to measure myocyte shortening. Intracellular Ca2+ was measured in cells loaded with the fluorescent indicator fura-2 AM. Whole-cell patch-clamp technique was employed to investigate the effect of AEA on the characteristics of APs. AEA (1 μM) caused a significant decrease in the amplitudes of electrically-evoked myocyte shortening and Ca2+ transients and significantly decreased the duration of AP. The effect of AEA on myocyte shortening and AP characteristics was not altered in the presence of pertussis toxin (PTX, 2 µg/ml for 4 h), AM251 and SR141716 (cannabinoid type 1 receptor antagonists) or AM630 and SR 144528 (cannabinoid type 2 receptor antagonists). Furthermore, AEA inhibited voltage-activated inward Na+ (INa) and Ca2+ (IL,Ca) currents; major ionic currents shaping the APs in ventricular myocytes, in a voltage and PTX-independent manner. Collectively, the results suggest that AEA depresses ventricular myocyte contractility, by decreasing the action potential duration (APD), and inhibits the function of voltage-dependent Na+ and L-type Ca2+ channels in a manner independent of cannabinoid receptors. This mechanism may be importantly involved in the antiarrhythmic effects of anandamide.Keywords: action potential, anandamide, cannabinoid receptor, endocannabinoid, ventricular myocytes
Procedia PDF Downloads 355804 Protective Effect of Diosgenin against Silica-Induced Tuberculosis in Rat Model
Authors: Williams A. Adu, Cynthia A. Danquah, Paul P. S. Ossei, Selase Ativui, Michael Ofori, James Asenso, George Owusu
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Background Silicosis is an occupational disease of the lung that is caused by chronic exposure to silica dust. There is a higher frequency of co-existence of silicosis with tuberculosis (TB), ultimately resulting in lung fibrosis and respiratory failure. Chronic intake of synthetic drugs has resulted in undesirable side effects. Diosgenin is a steroidal saponin that has been shown to exert a therapeutic effect on lung injury. Therefore, we investigated the ability of diosgenin to reduce the susceptibility of silica-induced TB in rats. Method Silicosis was induced by intratracheal instillation of 50 mg/kg crystalline silica in Sprague Dawley rats. Different doses of diosgenin (1, 10, and 100 mg/kg), Mycobacterium smegmatis and saline were administered for 30 days. Afterwards, 5 of the rats from each group were sacrificed, and the 5 remaining rats in each group, except the control, received Mycobacterium smegmatis. Treatment of diosgenin continued until the 50th day, and the rats were sacrificed at the end of the experiment. The result was analysed using a one-way analysis of variance (ANOVA) with a Graph-pad prism Result At a half-maximal inhibition concentration of 48.27 µM, diosgenin inhibited the growth of Mycobacterium smegmatis. There was a marked decline in the levels of immune cell infiltration and cytokines production. Lactate dehydrogenase and total protein levels were significantly reduced compared to control. There was an increase in the survival rate of the treatment group compared to the control. Conclusion Diosgenin ameliorated silica-induced pulmonary tuberculosis by declining the levels of inflammatory and pro-inflammatory cytokines and, in effect, significantly reduced the susceptibility of rats to pulmonary TB.Keywords: silicosis, tuberculosis, diosgenin, fibrosis, crystalline silica
Procedia PDF Downloads 65803 Effect of Electromagnetic Radiation on Reproductive System of Male Rat
Authors: Rohit Gautam, Kumari Vandana Singh, Jayprakash Nirala, Nina Nancy Murmu, Ramovatar Meena, Paulraj Rajamani
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Mobile phones have become a vital part of everyone’s life. Mobile phone and mobile phone towers emit RF-EMR (Radiofrequency Electromagnetic Radiation), which becomes a cause of concern to the general public. The study was designed to evaluate the effect of 3G (RF-EMR) on the reproductive system of male Wistar rats. Adult male Wistar rats were used for the study. Animals were divided into two groups, RF-exposed, and sham-exposed (control). RF-exposed rats were exposed to radio frequency radiation (2100 MHz) for 2 hours/day for 45 days. Emitted power density and specific absorption rate (SAR) values were measured during exposure. At the end of the exposure, testis and epididymis were excised out, and their weights were recorded. Sperm cell count, morphology, viability, and reactive oxygen species (ROS) levels were checked. Lipid peroxidation and sperm mitochondrial activity were measured. Histopathology of testis and ultrastructure analysis of sperm were also checked. Result showed a decrease in organ weight and sperm count with alteration in the sperm morphology in exposed group rats. A significant decrease in sperm viability, membrane integrity, and mitochondrial activity was found. Also, an increase in lipid peroxidation and ROS level were found in exposed group animals as compared to control. It may be concluded that exposure to radiofrequency radiation emits from mobile phones leads to oxidative stress-mediated changes in reproductive parameters.Keywords: electromagnetic radiation, oxidative stress, reactive oxygen species, sperm
Procedia PDF Downloads 178802 Study of a Cross-Flow Membrane to a Kidney Encapsulation Engineering Structures for Immunosuppression Filter
Authors: Sihyun Chae, Ryoto Arai, Waldo Concepcion, Paula Popescu
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The kidneys perform an important role in the human hormones that regulate the blood pressure, produce an active form of vitamin D and control the production of red blood cells. Kidney disease can cause health problems, such as heart disease. Also, increase the chance of having a stroke or heart attack. There are mainly to types of treatments for kidney disease, dialysis, and kidney transplant. For a better quality of life, the kidney transplant is desirable. However, kidney transplant can cause antibody reaction and patients’ body would be attacked by immune system of their own. For solving that issue, patients with transplanted kidney always take immunosuppressive drugs which can hurt kidney as side effects. Patients willing to do a kidney transplant have a waiting time of 3.6 years in average searching to find an appropriate kidney, considering there are almost 96,380 patients waiting for kidney transplant. There is a promising method to solve these issues: bioartificial kidney. Our membrane is specially designed with unique perforations capable to filter the blood cells separating the white blood cells from red blood cells. White blood cells will not pass through the encapsulated kidney preventing the immune system to attack the new organ and eliminating the need of a matching donor. It is possible to construct life-time long encapsulation without needing pumps or a power supply on the cell’s separation method preventing futures surgeries due the Cross-Channel Flow inside the device. This technology allows the possibility to use an animal kidney, prevent cancer cells to spread through the body, arm and leg transplants in the future. This project aims to improve the quality of life of patients with kidney disease.Keywords: kidney encapsulation, immunosuppression filter, leukocyte filter, leukocyte
Procedia PDF Downloads 201801 Fabrication and Characterization of Folic Acid-Grafted-Thiomer Enveloped Liposomes for Enhanced Oral Bioavailability of Docetaxel
Authors: Farhan Sohail, Gul Shahnaz Irshad Hussain, Shoaib Sarwar, Ibrahim Javed, Zajif Hussain, Akhtar Nadhman
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The present study was aimed to develop a hybrid nanocarrier (NC) system with enhanced membrane permeability, bioavailability and targeted delivery of Docetaxel (DTX) in breast cancer. Hybrid NC’s based on folic acid (FA) grafted thiolated chitosan (TCS) enveloped liposomes were prepared with DTX and evaluated in-vitro and in-vivo for their enhanced permeability and bioavailability. Physicochemical characterization of NC’s including particle size, morphology, zeta potential, FTIR, DSC, PXRD, encapsulation efficiency and drug release from NC’s was determined in vitro. Permeation enhancement and p-gp inhibition were performed through everted sac method on freshly excised rat intestine which indicated that permeation was enhanced 5 times as compared to pure DTX and the hybrid NC’s were strongly able to inhibit the p-gp activity as well. In-vitro cytotoxicity and tumor targeting was done using MDA-MB-231 cell line. The stability study of the formulations performed for 3 months showed the improved stability of FA-TCS enveloped liposomes in terms of its particles size, zeta potential and encapsulation efficiency as compared to TCS NP’s and liposomes. The pharmacokinetic study was performed in vivo using rabbits. The oral bioavailability and AUC0-96 was increased 10.07 folds with hybrid NC’s as compared to positive control. Half-life (t1/2) was increased 4 times (58.76 hrs) as compared to positive control (17.72 hrs). Conclusively, it is suggested that FA-TCS enveloped liposomes have strong potential to enhance permeability and bioavailability of hydrophobic drugs after oral administration and tumor targeting.Keywords: docetaxel, coated liposome, permeation enhancement, oral bioavailability
Procedia PDF Downloads 408800 Experimental Research on Neck Thinning Dynamics of Droplets in Cross Junction Microchannels
Authors: Yilin Ma, Zhaomiao Liu, Xiang Wang, Yan Pang
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Microscale droplets play an increasingly important role in various applications, including medical diagnostics, material synthesis, chemical engineering, and cell research due to features of high surface-to-volume ratio and tiny scale, which can significantly improve reaction rates, enhance heat transfer efficiency, enable high-throughput parallel studies as well as reduce reagent usage. As a mature technique to manipulate small amounts of liquids, droplet microfluidics could achieve the precise control of droplet parameters such as size, uniformity, structure, and thus has been widely adopted in the engineering and scientific research of multiple fields. Necking processes of the droplet in the cross junction microchannels are experimentally and theoretically investigated and dynamic mechanisms of the neck thinning in two different regimes are revealed. According to evolutions of the minimum neck width and the thinning rate, the necking process is further divided into different stages and the main driving force during each stage is confirmed. Effects of the flow rates and the cross-sectional aspect ratio on the necking process as well as the neck profile at different stages are provided in detail. The distinct features of the two regimes in the squeezing stage are well captured by the theoretical estimations of the effective flow rate and the variations of the actual flow rates in different channels are reasonably reflected by the channel width ratio. In the collapsing stage, the quantitative relation between the minimum neck width and the remaining time is constructed to identify the physical mechanism.Keywords: cross junction, neck thinning, force analysis, inertial mechanism
Procedia PDF Downloads 110799 Protein Feeding Pattern, Casein Feeding, or Milk-Soluble Protein Feeding did not Change the Evolution of Body Composition during a Short-Term Weight Loss Program
Authors: Solange Adechian, Michèle Balage, Didier Remond, Carole Migné, Annie Quignard-Boulangé, Agnès Marset-Baglieri, Sylvie Rousset, Yves Boirie, Claire Gaudichon, Dominique Dardevet, Laurent Mosoni
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Studies have shown that timing of protein intake, leucine content, and speed of digestion significantly affect postprandial protein utilization. Our aim was to determine if one can spare lean body mass during energy restriction by varying the quality and the timing of protein intake. Obese volunteers followed a 6-wk restricted energy diet. Four groups were compared: casein pulse, casein spread, milk-soluble protein (MSP, = whey) pulse, and MSP spread (n = 10-11 per group). In casein groups, caseins were the only protein source; it was MSP in MSP groups. Proteins were distributed in four meals per day in the proportion 8:80:4:8% in the pulse groups; it was 25:25:25:25% in the spread groups. We measured weight, body composition, nitrogen balance, 3-methylhistidine excretion, perception of hunger, plasma parameters, adipose tissue metabolism, and whole body protein metabolism. Volunteers lost 7.5 ± 0.4 kg of weight, 5.1 ± 0.2 kg of fat, and 2.2 ± 0.2 kg of lean mass, with no difference between groups. In adipose tissue, cell size and mRNA expression of various genes were reduced with no difference between groups. Hunger perception was also never different between groups. In the last week, due to a higher inhibition of protein degradation and despite a lower stimulation of protein synthesis, postprandial balance between whole body protein synthesis and degradation was better with caseins than with MSP. It seems likely that the positive effect of caseins on protein balance occurred only at the end of the experiment.Keywords: lean body mass, fat mass, casein, whey, protein metabolism
Procedia PDF Downloads 72798 Aza-Flavanones as Small Molecule Inhibitors of MicroRNA-10b in MDA-MB-231 Breast Cancer Cells
Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra
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MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.Keywords: breast cancer, microRNA, metastasis, EMT
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