Search results for: NK cell expansion
Commenced in January 2007
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Edition: International
Paper Count: 4770

Search results for: NK cell expansion

2970 Morphological Process of Villi Detachment Assessed by Computer-Assisted 3D Reconstruction of Intestinal Crypt from Serial Ultrathin Sections of Rat Duodenum Mucosa

Authors: Lise P. Labéjof, Ivna Mororó, Raquel G. Bastos, Maria Isabel G. Severo, Arno H. de Oliveira

Abstract:

This work presents an alternative mode of intestine mucosa renewal that may allow to better understand the total loss of villi after irradiation. It was tested a morphological method of 3d reconstruction using micrographs of serial sections of rat duodenum. We used hundreds of sections of each specimen of duodenum placed on glass slides and examined under a light microscope. Those containing the detachment, approximately a dozen, were chosen for observation under a transmission electron microscope (TEM). Each of these sections was glued on a block of epon resin and recut into a hundred of 60 nm-thick sections. Ribbons of these ultrathin sections were distributed on a series of copper grids in the same order of appearance than during the process of microstomia. They were then stained by solutions of uranyl and lead salts and observed under a TEM. The sections were pictured and the electron micrographs showing signs of cells detachment were transferred into two softwares, ImageJ to align the cellular structures and Reconstruct to realize the 3d reconstruction. It has been detected epithelial cells that exhibited all signs of programmed cell death and localized at the villus-crypt junction. Their nucleus was irregular in shape with a condensed chromatin in clumps. Their cytoplasm was darker than that of neighboring cells, containing many swollen mitochondria. In some places of the sections, we could see intercellular spaces enlarged by the presence of shrunk cells which displayed a plasma membrane with an irregular shape in thermowell as if the cell interdigitations would distant from each other. The three-dimensional reconstruction of the crypts has allowed observe gradual loss of intercellular contacts of crypt cells in the longitudinal plan of the duodenal mucosa. In the transverse direction, there was a gradual increase of the intercellular space as if these cells moved away from one another. This observation allows assume that the gradual remoteness of the cells at the villus-crypt junction is the beginning of the mucosa detachment. Thus, the shrinking of cells due to apoptosis is the way that they detach from the mucosa and progressively the villi also. These results are in agreement with our initial hypothesis and thus have demonstrated that the villi become detached from the mucosa at the villus-crypt junction by the programmed cell death process. This type of loss of entire villus helps explain the rapid denudation of the intestinal mucosa in case of irradiation.

Keywords: 3dr, transmission electron microscopy, ionizing radiations, rat small intestine, apoptosis

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2969 Education as a Factor Which Reduces Poverty

Authors: E. V. Fakhrutdinova, Y. S. Kolesnikova, E. A. Karasik, V. M. Zagidullina

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Poverty as the social and economic phenomenon exists in any society and represents a many-sided problem. In this sense it is universal and for many centuries serves as a research objects for scientists. Special attention to a problem of poverty in Russia is caused, first of all, by the critical growth of inequality and by scales of expansion of poverty, considerable decrease in the level and quality of life of the population, decrease in availability of education during the period of reforming. The expansion of poverty on the working members of society, youth, which has to provide reproduction of the population is alarming. As poverty is the reason of weakening of national security of the country, degradation of the population, decline in the quality of the human capital, complication of a demographic situation, strengthening of social contradictions in society, so far as the reduction of poverty, so, the increase in production. Poverty: the characteristic of an economic situation of the individual or social group at which they can't satisfy certain minimum requirements necessary for life, preservations of working capacity and reproduction. Poverty became one of the critical factors expelling people from the system of the institutional interactions reducing social space in which their relations were building breaking their social identity. Complication of the problem of poverty in modern society happened due to penetration of the related relations into many spheres of life. It is known that negative consequences of poverty display not only at the personal level of the poor person, but also at the level of interpersonal social interactions, decline in the quality and level of development of the human capital, and also at social and economic system in general. We conducted a research on the influence of education on the change of poverty level of the population. We consider education as a resource for an increase of the income and social mobility. Dependence of the income of the population on the level of education, availability of education (level of education and quality of education) on the level of income of families is found. Differentiation of quality and number of educational services for children depending on the level of the income of families is revealed. Influence of a factor of poverty on the availability of education is also studied. We consider expenses on education as the limiter of access to education. We consider education as a factor of fixation and aggravation of a property inequality. In the solution of problems of poverty the defining condition is the state regulation of social and economic development by means of creation of the effective institutional environment. The state has to develop measures for an increase of availability of various services to all categories of citizens, in particular services of health care and education, especially for poor citizens enters. The special attention regarding an increase of availability of education services has to be paid to creation of system of social elevators.

Keywords: poverty, education, human capital, quality of life

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2968 Strategies for Improving and Sustaining Quality in Higher Education

Authors: Anshu Radha Aggarwal

Abstract:

Higher Education (HE) in the India has experienced a series of remarkable changes over the last fifteen years as successive governments have sought to make the sector more efficient and more accountable for investment of public funds. Rapid expansion in student numbers and pressures to widen Participation amongst non-traditional students are key challenges facing HE. Learning outcomes can act as a benchmark for assuring quality and efficiency in HE and they also enable universities to describe courses in an unambiguous way so as to demystify (and open up) education to a wider audience. This paper examines how learning outcomes are used in HE and evaluates the implications for curriculum design and student learning. There has been huge expansion in the field of higher education, both technical and non-technical, in India during the last two decades, and this trend is continuing. It is expected that another about 400 colleges and 300 universities will be created by the end of the 13th Plan Period. This has lead to many concerns about the quality of education and training of our students. Many studies have brought the issues ailing our curricula, delivery, monitoring and assessment. Govt. of India, (via MHRD, UGC, NBA,…) has initiated several steps to bring improvement in quality of higher education and training, such as National Skills Qualification Framework, making accreditation of institutions mandatory in order to receive Govt. grants, and so on. Moreover, Outcome-based Education and Training (OBET) has also been mandated and encouraged in the teaching/learning institutions. MHRD, UGC and NBAhas made accreditation of schools, colleges and universities mandatory w.e.f Jan 2014. Outcome-based Education and Training (OBET) approach is learner-centric, whereas the traditional approach has been teacher-centric. OBET is a process which involves the re-orientation/restructuring the curriculum, implementation, assessment/measurements of educational goals, and achievement of higher order learning, rather than merely clearing/passing the university examinations. OBET aims to bring about these desired changes within the students, by increasing knowledge, developing skills, influencing attitudes and creating social-connect mind-set. This approach has been adopted by several leading universities and institutions around the world in advanced countries. Objectives of this paper is to highlight the issues concerning quality in higher education and quality frameworks, to deliberate on the various education and training models, to explain the outcome-based education and assessment processes, to provide an understanding of the NAAC and outcome-based accreditation criteria and processes and to share best-practice outcomes-based accreditation system and process.

Keywords: learning outcomes, curriculum development, pedagogy, outcome based education

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2967 Supplementation of Yeast Cell Wall on Growth Performance in Broiler Reared under High Ambient Temperature

Authors: Muhammad Shahzad Hussain

Abstract:

Two major problems are facing generally by conventional poultry farming that is disease outbreaks and poor performance, which results due to improper management. To enhance the growth performance and efficiency of feed and reduce disease outbreaks, antibiotic growth promoters (AGPs) which are antibiotics at sub-therapeutic levels, are extensively used in the poultry industry. European Union has banned the use of antibiotics due to their presence in poultry products, development of antibiotic-resistant pathogens, and disturbance of normal gut microbial ecology. These residues cause serious health concerns and produce antibiotic resistance in pathogenic microbes in human beings. These issues strengthen the need for the withdrawal of AGPs from poultry feed. Nowadays, global warming is a major issue, and it is more critical in tropical areas like Pakistan, where heat stress is already a major problem. Heat stress leads to poor production performance, high mortality, immuno-suppression, and concomitant diseases outbreak. The poultry feed industry in Pakistan, like other countries of the world, has been facing shortages and high prices of local as well as imported feed ingredients. Prebiotics are potential replacer for AGP as prebiotics has properties to enhance the production potential and reduce the growth of harmful bacteria as well as stimulate the growth/activity of beneficial bacteria. The most commonly used prebiotics in poultry includes mannan oligosaccharide (MOS). MOS is an essential component of the yeast cell wall (YCW) (Saccharomyces cerevisiae); therefore, the YCW wall possesses prebiotic properties. The use of distillery yeast wall (YCW) has the potential to replace conventional AGPs and to reduce mortality due to heat stress as well as to bind toxins in the feed. The dietary addition of YCW has not only positive effects on production performance in poultry during normal conditions but during stressful conditions. A total of 168-day-old broilers were divided into 6 groups, each of which has 28 birds with 4 replicates (n=7).Yeast cell wall (YCW) supplementation @ 0%, 1%, 1.5%, 2%, 2.5%, 3% from day 0 to 35. Heat stress was exposed from day 21 to 35 at 30±1.1ᵒC with relative humidity 65±5%. Zootechnical parameters like body weight, FCR, Organ development, and histomorphometric parameters were studied. A significant weight gain was observed at group C supplemented @ 1.5% YCW during the fifth week. Significant organ weight gain of Gizzard, spleen, small intestine, and cecum was observed at group C supplemented @ 1.5% YCW. According to morphometric indices Duodenum, Jejunum, and Ileum has significant villus height, while Jejunum and Ileum have also significant villus surface area in the group supplemented with 1.5% YCW. IEL count was only decreased in 1.5% YCW-fed group in jejunum and ileum, not in duodenum, that was less in 2% YCW-supplemented group. Dietary yeast cell wall of saccharomyces cerevisiae partially reduced the effects of high ambient temperature in terms of better growth and modified gut histology and components of mucosal immune response to better withstand heat stress in broilers.

Keywords: antibiotics, AGPs, broilers, MOS, prebiotics, YCW

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2966 Electrodeposition of Silicon Nanoparticles Using Ionic Liquid for Energy Storage Application

Authors: Anjali Vanpariya, Priyanka Marathey, Sakshum Khanna, Roma Patel, Indrajit Mukhopadhyay

Abstract:

Silicon (Si) is a promising negative electrode material for lithium-ion batteries (LiBs) due to its low cost, non-toxicity, and a high theoretical capacity of 4200 mAhg⁻¹. The primary challenge of the application of Si-based LiBs is large volume expansion (~ 300%) during the charge-discharge process. Incorporation of graphene, carbon nanotubes (CNTs), morphological control, and nanoparticles was utilized as effective strategies to tackle volume expansion issues. However, molten salt methods can resolve the issue, but high-temperature requirement limits its application. For sustainable and practical approach, room temperature (RT) based methods are essentially required. Use of ionic liquids (ILs) for electrodeposition of Si nanostructures can possibly resolve the issue of temperature as well as greener media. In this work, electrodeposition of Si nanoparticles on gold substrate was successfully carried out in the presence of ILs media, 1-butyl-3-methylimidazolium-bis (trifluoromethyl sulfonyl) imide (BMImTf₂N) at room temperature. Cyclic voltammetry (CV) suggests the sequential reduction of Si⁴⁺ to Si²⁺ and then Si nanoparticles (SiNs). The structure and morphology of the electrodeposited SiNs were investigated by FE-SEM and observed interconnected Si nanoparticles of average particle size ⁓100-200 nm. XRD and XPS data confirm the deposition of Si on Au (111). The first discharge-charge capacity of Si anode material has been found to be 1857 and 422 mAhg⁻¹, respectively, at current density 7.8 Ag⁻¹. The irreversible capacity of the first discharge-charge process can be attributed to the solid electrolyte interface (SEI) formation via electrolyte decomposition, and trapped Li⁺ inserted into the inner pores of Si. Pulverization of SiNs results in the creation of a new active site, which facilitates the formation of new SEI in the subsequent cycles leading to fading in a specific capacity. After 20 cycles, charge-discharge profiles have been stabilized, and a reversible capacity of 150 mAhg⁻¹ is retained. Electrochemical impedance spectroscopy (EIS) data shows the decrease in Rct value from 94.7 to 47.6 kΩ after 50 cycles of charge-discharge, which demonstrates the improvements of the interfacial charge transfer kinetics. The decrease in the Warburg impedance after 50 cycles of charge-discharge measurements indicates facile diffusion in fragmented and smaller Si nanoparticles. In summary, Si nanoparticles deposited on gold substrate using ILs as media and characterized well with different analytical techniques. Synthesized material was successfully utilized for LiBs application, which is well supported by CV and EIS data.

Keywords: silicon nanoparticles, ionic liquid, electrodeposition, cyclic voltammetry, Li-ion battery

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2965 Mechanical Properties of Kenaf Reinforced Composite with Different Fiber Orientation

Authors: Y. C. Ching, K. H. Chong

Abstract:

The increasing of environmental awareness has led to grow interest in the expansion of materials with eco-friendly attributes. In this study, a 3 ply sandwich layer of kenaf fiber reinforced unsaturated polyester with various fiber orientations was developed. The effect of the fiber orientation on mechanical and thermal stability properties of polyester was studied. Unsaturated polyester as a face sheets and kenaf fibers as a core was fabricated with combination of hand lay-up process and cold compression method. Tested result parameters like tensile, flexural, impact strength, melting point, and crystallization point were compared and recorded based on different fiber orientation. The failure mechanism and property changes associated with directional change of fiber to polyester composite were discussed.

Keywords: kenaf fiber, polyester, tensile, thermal stability

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2964 Dalit Struggle in Nepal: From Invoking Dalit to Becoming Part of the Nepalese Power

Authors: Mom Bishwakarma

Abstract:

This research traces out how the Dalit in Nepal evolved from the early 1950s to the current day, from invoking Dalit against caste discrimination through to the asserting proportional representation in state structures. The research focused most closely on the formation of Dalit association and resistance, as well as on the different struggles throughout this period. It then discusses the expansion of Dalit movement in NGOs, its internationalization and responses. The research sees that Dalit movement has been influenced by its network with the national and international civil rights movement particularly Dalit movement in India and argues that Dalit movement in Nepal have in many ways, challenged the orthodox based caste stratification for Dalit equality and justice. It can be seen that at the same time as Dalit participation was increasing, divisions by caste line also emerged. Rather reshaping the power structures, Dalit movement encircled into division and contentious politics.

Keywords: Dalit, equality, justice, movements, Nepal

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2963 The Effect of Micro/Nano Structure of Poly (ε-caprolactone) (PCL) Film Using a Two-Step Process (Casting/Plasma) on Cellular Responses

Authors: JaeYoon Lee, Gi-Hoon Yang, JongHan Ha, MyungGu Yeo, SeungHyun Ahn, Hyeongjin Lee, HoJun Jeon, YongBok Kim, Minseong Kim, GeunHyung Kim

Abstract:

One of the important factors in tissue engineering is to design optimal biomedical scaffolds, which can be governed by topographical surface characteristics, such as size, shape, and direction. Of these properties, we focused on the effects of nano- to micro-sized hierarchical surface. To fabricate the hierarchical surface structure on poly(ε-caprolactone) (PCL) film, we employed a micro-casting technique by pressing the mold and nano-etching technique using a modified plasma process. The micro-sized topography of PCL film was controlled by sizes of the micro structures on lotus leaf. Also, the nano-sized topography and hydrophilicity of PCL film were controlled by a modified plasma process. After the plasma treatment, the hydrophobic property of the PCL film was significantly changed into hydrophilic property, and the nano-sized structure was well developed. The surface properties of the modified PCL film were investigated in terms of initial cell morphology, attachment, and proliferation using osteoblast-like-cells (MG63). In particular, initial cell attachment, proliferation and osteogenic differentiation in the hierarchical structure were enhanced dramatically compared to those of the smooth surface. We believe that these results are because of a synergistic effect between the hierarchical structure and the reactive functional groups due to the plasma process. Based on the results presented here, we propose a new biomimetic surface model that maybe useful for effectively regenerating hard tissues.

Keywords: hierarchical surface, lotus leaf, nano-etching, plasma treatment

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2962 Seroprevalence and Associated Factors of Hepatitis B and Hepatitis C Viral Infections Among Prisoners in Tigray, Northern Ethiopia

Authors: Belaynesh Tsegay, Teklay Gebrecherkos, Atsebaha Gebrekidan Kahsay, Mahmud Abdulkader

Abstract:

Background: Hepatitis B and C viruses are important health and socioeconomic problem across the globe, with a remarkable number of diseases and deaths in sub-Saharan African countries. The burden of hepatitis is unknown in the prison settings of Tigray. Therefore, we aimed to describe the seroprevalence and associated factors of hepatitis B and C viruses among prisoners in Tigray, Ethiopia. Methods: A cross-sectional study was carried out from February 2020 to May 2020 at the prison facilities of Tigray. Demographics and associated factors were collected from 315 prisoners prospectively. Five milliliters of blood were collected and tested using rapid tests kits of HBsAg (Zhejiang orient Gene Biotech Co., Ltd., China) and HCV antibodies (Volkan Kozmetik Sanayi Ve Ticaret Ltd. STI, Turkey). Positive samples were confirmed using ELISA (Beijing Wantai Biological Pharmacy Enterprise Co. Ltd). Data were analyzed using the SPSS version 20, and p<0.05 was considered statistically significant. Results: The overall seroprevalence of HBV and HCV were 25 (7.9%) and 1 (0.3%), respectively. The majority of hepatitis B viral infections were identified from the age groups of 18–25 years (10.7%) and unmarried prisoners (11.8%). Prisoners greater than 100 per cell (AOR=3.95, 95% CI=1.15–13.6, p=0.029) and with a history of alcohol consumption (AOR=3.01, 95% CI=1.17–7.74, p=0.022) were significantly associated with HBV infections. Conclusion: The seroprevalence of HBV among prisoners was nearly high or borderline, with a very low HCV prevalence. HBV was most prevalent among young adults, those housed with a large number of prisoners per cell, and those who had a history of alcohol consumption. This study recommends that there should be prison-focused intervention, including regular health education, with the emphasis on the mode of transmission and introducing HBV screening policy for prisoners, especially when they enter the prison.

Keywords: seroprevalence, HBV, HCV, prisoners, tigray

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2961 Survey of the Effect of the Probiotic Bacterium Lactobacillus plantarum and Streptococcus mutans on Casp3, AKT/PTEN, and MAPK Signaling Pathways at Co-Culture with KB Oral Cancer Cell Line and HUVEC Cells

Authors: Negar Zaheddoust, Negin Zaheddoust, Abbas Asoudeh-Fard

Abstract:

Probiotic bacteria have been employed as a novel and less side-effect strategy for anticancer therapy. Since the oral cavity is a host for probiotic and pathogen bacteria to colonize, more investigation is needed to evaluate the effectiveness of this novel adjunctive treatment for oral cancer. We considered Lactobacillus plantarum as a probiotic and Streptococcus mutans as a pathogen bacterium in our study. The aim of this study is to examine the effect of Lactobacillus plantarum and Streptococcus mutans on Casp3, AKT / PTEN, and MAPK signaling pathway, which is involved in apoptosis or survival of oral cancer KB cells. On the other hand, to study the effects of these bacteria on normal cells, we used HUVEC cells. The KB and HUVEC cell lines were co-cultured with Lactobacillus plantarum and Streptococcus mutans isolated from traditional Iranian dairy and dental plaque, respectively. The growth-inhibitory effects of these two bacteria on KB and HUVEC cells were determined by (3-(4, 5-dimethylthiazolyl-2)-2,5diphenyltetrazolium bromide) MTT assay. MTT results demonstrated that the proliferation of KB cells was affected in a time, dose, and strain-dependent manner. In the following, the examination of induced apoptosis or necrosis in co-cultured KB cells with the best IC50 concentration of the Lactobacillus plantarum and Streptococcus mutans will be analyzed by FACS flow cytometry, and the changes in gene expression of Casp3, AKT / PTEN, MAPK genes will be evaluated using real-time polymerase chain reaction.

Keywords: cancer therapy, induced apoptosis, oral cancer, probiotics

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2960 Mechanical Properties of Young and Senescence Fibroblast Cells Using Passive Microrheology

Authors: Samira Khalaji, , Fenneke Klein Jan, Kay-E. Gottschalk, Eugenia Makrantonaki, Karin Scharffetter-Kochanek

Abstract:

Biological aging is a multi-dimensional process that takes place over a whole range of scales from the nanoscopic alterations within individual cells, over transformations in tissues and organs and to changes of the whole organism. On the single cell level, aging involves mutation of genes, differences in gene expression levels as well as altered posttranslational modifications of proteins. A variety of proteins is affected, including proteins of the cell cytoskeleton and migration machinery. Previous work quantified the expression of cytoskeleton proteins on the gene and protein levels in senescent and young fibroblasts. Their results show that senescent skin fibroblasts have an upregulated expression of the intermediate filament (IF) protein vimentin in contrast to actin and tubulin, which are downregulated. IFs play an important role in providing mechanical stability of cells. However, the mechanical properties of IFs depending on cellular senescence or age of the donor has not been studied so far. Hence, we employed passive microrheology on primary human dermal fibroblasts from female donors with age of 28 years (young) and 86 years (old) as model of in vivo aging and human normal dermal fibroblast from 11-year old male with CPD 17-35 (young) and CPD 58-59 (senescence) as a model of in vitro replicative senescence. In contrast to the expectations, our primary results show no significant differences in the viscoelastic properties of fibroblasts depending on age of the donor or cellular replicative senescence.

Keywords: aging, cytoskeleton, fibroblast, mechanical properties

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2959 Taxonomic Analyses of Some Members of Cucurbitoideae Using Phytolith Marker

Authors: J. K. Ebigwai, E. Asuquo

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Systematic affinities among Cucurbitaceae members are highly debatable as exemplified by diverging views on their phylogenies. Worst still is the overriding reliance on morphometric marker in the delimitation of cucurbitoideae members. Considerable symplesiomorphic and synapmorphic character states have been observed among some members of same genera than do with some members of other genera. The broad study aims at establishing phylogenies among species of Cucumis (Melothrieae), Momordica, Telfairia (Jolliffieae), Trichosanthes (Trichosantheae), Citrullus, Lagenaria, Luffa (Benincaseae) and Cucurbita (Cucurbita) using anatomical, cytological, Palynological, serological, and phytolith markers. However, this paper shall present preliminary findings on the phytolith character states for Cucumis melo, Momordica charantia, Telfairia occidentales, Trichosanthes dioica, Citrullus vulgaris, Lagenaria siceraria, Luffa cylindrical, Cucurbita pepo and Cucurbita maxima. Heavy liquid floatation method was employed in the extraction of the phytolith matter from the leaf tissues of these species. The result revealed that a bilobate short cell and a trapeziform sinuate form were absent in all the species except in Cucumis melo, Citrullus vulgaris and Lagenaria siceraria. Also a globular granulate form was observed exclusively in Telfairia occidentales, Cucurbita maxima, Momordica charantia and Luffa cylindrical. Other forms of phytolith observed were not diagnostic as they were not species specific. The results tentatively suggests a closer examination of the existing classification system.

Keywords: bilobate short cell, cucums, phytolith, telfairia, trapeziform sinuate

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2958 Cellular Technologies in Urology

Authors: R. Zhankina, U. Zhanbyrbekuly, A. Tamadon, M. Askarov, R. Sherkhanov, D. Akhmetov, D. Saipiyeva, N. Keulimzhaev

Abstract:

Male infertility affects about 15% of couples of reproductive age. Approximately 10–15% have azoospermia who have previously been diagnosed with male infertility. Azoospermia is regarded as the absence of spermatozoa in the ejaculate and is found in 10-15% of infertile men. Non-obstructive azoospermia is considered a cause of male infertility that is not amenable to drug therapy. Patients with non-obstructive azoospermia are unable to have their "own" children and have only options for adoption or use of donor sperm. Advances in assisted reproductive technologies such as intracytoplasmic sperm injection in vitro fertilization have significantly changed the management of patients with non-obstructive azoospermia. Advances in biotechnology have increased the options for treating patients with non-obstructive azoospermia. Mesenchymal stem cell therapy has been recognized as a new option for infertility treatment. Material and methods of the study: After obtaining informed consent, 5 patients diagnosed with non-obstructive azoospermia were included in an open, non-randomized study. The age of the patients ranged from 24 to 35 years. The examination was carried out before the start of treatment, which included biochemical blood tests, hormonal profile levels (luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, inhibin B); tests for tumor markers; genetic research. All studies were carried out in compliance with the requirements of Protocol No. 8 dated 06/09/20, approved by the Local Ethical Commission of NJSC "Astana Medical University". The control examination of patients was carried out after 6 months, by re-taking the program and hormonal profile (testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, inhibin B). Before micro-TESE of the testis, all 5 patients underwent myeloexfusion in the operating room. During the micro-TESE, autotransplantation of mesenchymal stem cells into the testicular network, previously cultured in a cell technology laboratory for 2 weeks, was performed. Results of the study: in all patients, the levels of total testosterone increased, the level of follicle-stimulating hormone decreased, the levels of luteinizing hormone returned to normal, the level of inhibin B increased. IVF with a positive result; another patient (20%) had spermatogenesis cells. Non-obstructive azoospermia and mesenchymal stem cells Conclusions: The positive results of this work serve as the basis for the application of a new cellular therapeutic approach for the treatment of non-obstructive azoospermia using mesenchymal stem cells.

Keywords: cell therapy, regenerative medicine, male infertility, mesenchymal stem cells

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2957 An Aptasensor Based on Magnetic Relaxation Switch and Controlled Magnetic Separation for the Sensitive Detection of Pseudomonas aeruginosa

Authors: Fei Jia, Xingjian Bai, Xiaowei Zhang, Wenjie Yan, Ruitong Dai, Xingmin Li, Jozef Kokini

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Pseudomonas aeruginosa is a Gram-negative, aerobic, opportunistic human pathogen that is present in the soil, water, and food. This microbe has been recognized as a representative food-borne spoilage bacterium that can lead to many types of infections. Considering the casualties and property loss caused by P. aeruginosa, the development of a rapid and reliable technique for the detection of P. aeruginosa is crucial. The whole-cell aptasensor, an emerging biosensor using aptamer as a capture probe to bind to the whole cell, for food-borne pathogens detection has attracted much attention due to its convenience and high sensitivity. Here, a low-field magnetic resonance imaging (LF-MRI) aptasensor for the rapid detection of P. aeruginosa was developed. The basic detection principle of the magnetic relaxation switch (MRSw) nanosensor lies on the ‘T₂-shortening’ effect of magnetic nanoparticles in NMR measurements. Briefly speaking, the transverse relaxation time (T₂) of neighboring water protons get shortened when magnetic nanoparticles are clustered due to the cross-linking upon the recognition and binding of biological targets, or simply when the concentration of the magnetic nanoparticles increased. Such shortening is related to both the state change (aggregation or dissociation) and the concentration change of magnetic nanoparticles and can be detected using NMR relaxometry or MRI scanners. In this work, two different sizes of magnetic nanoparticles, which are 10 nm (MN₁₀) and 400 nm (MN₄₀₀) in diameter, were first immobilized with anti- P. aeruginosa aptamer through 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) chemistry separately, to capture and enrich the P. aeruginosa cells. When incubating with the target, a ‘sandwich’ (MN₁₀-bacteria-MN₄₀₀) complex are formed driven by the bonding of MN400 with P. aeruginosa through aptamer recognition, as well as the conjugate aggregation of MN₁₀ on the surface of P. aeruginosa. Due to the different magnetic performance of the MN₁₀ and MN₄₀₀ in the magnetic field caused by their different saturation magnetization, the MN₁₀-bacteria-MN₄₀₀ complex, as well as the unreacted MN₄₀₀ in the solution, can be quickly removed by magnetic separation, and as a result, only unreacted MN₁₀ remain in the solution. The remaining MN₁₀, which are superparamagnetic and stable in low field magnetic field, work as a signal readout for T₂ measurement. Under the optimum condition, the LF-MRI platform provides both image analysis and quantitative detection of P. aeruginosa, with the detection limit as low as 100 cfu/mL. The feasibility and specificity of the aptasensor are demonstrated in detecting real food samples and validated by using plate counting methods. Only two steps and less than 2 hours needed for the detection procedure, this robust aptasensor can detect P. aeruginosa with a wide linear range from 3.1 ×10² cfu/mL to 3.1 ×10⁷ cfu/mL, which is superior to conventional plate counting method and other molecular biology testing assay. Moreover, the aptasensor has a potential to detect other bacteria or toxins by changing suitable aptamers. Considering the excellent accuracy, feasibility, and practicality, the whole-cell aptasensor provides a promising platform for a quick, direct and accurate determination of food-borne pathogens at cell-level.

Keywords: magnetic resonance imaging, meat spoilage, P. aeruginosa, transverse relaxation time

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2956 The Effects of Expanding the Generosity of the Statutory Sick Leave Insurance: The Case of a French Reform

Authors: Mohamed Ali Benhalima, Nathon Elbaz, Malik Koubi

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This paper evaluates an expansion of employer-mandated sick leave insurance in the French private sector. We use a difference-in-differences method in which control groups are defined according to the collective bargaining agreement (CBA) employees belong to. Indeed, thanks to complementary insurance provided by CBAs, employees were not affected the same way by the reform. We find significant effects of the reform on sick leave spells lasting at least 7 days, consistently with the reform target. The effects on spells’ duration and frequency are positive and more pronounced for women than for men, for whom the effect on frequency tends to be slightly negative. The effects are also more pronounced for executives and supervisors than less qualified categories.

Keywords: sickness absence, collective agreements, daily sickness benefits, labor economics

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2955 The Hepatoprotective Effects of Aquatic Extract of Levesticum Officinale against Paraquat Toxicity of Hepatocytes

Authors: Hasan Afarnegan, Ali Shahraki, Jafar Shahraki

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Paraquat is widely used as a strong nitrogen-based herbicide for controlling of weeds in agriculture. This poison is extremely toxic for humans which induces several – organ failure by accumulation in cells and many instances of death occurred due to its poisoning. Paraquat metabolized primarily in the liver. The purpose of this study was to assess the effects of aquatic extract of levisticum officinale on oxidative status and biochemical factors in hepatocytes exposed to paraquat. Our results determined that hepatocytes destruction induced by paraquat is mediated by reactive oxygen species (ROS) production, lipid peroxidation and decrease of mitochondrial membrane potential were significantly (P<0.05) prevented by aquatic extract of Levisicum officinale (100, 200 and 300 µg/ml). These effects of paraquat also prevented via antioxidants and ROS scavengers (α-tocopherol, DMSO, manitol), mitochondrial permeability transition (MPT) pore sealing compound (carnitine).MPT pore sealing compound inhibited the hepatotoxicity, indicating that paraquat induced cell death via mithochondrial pathway. Pretreatment of hepatocytes with aquatic extracts of Levisticum officinale, antioxidants and ROS scavengers also blocked hepatic cell death caused by paraquat, suggesting that oxidative stress may be directly induced decline of mithochondrial membrane potential. In conclusion, paraquat hepatotoxicity can be attributed to oxidative stress and continued by mithochondrial membrane potential disruption. Levisticum officinale aquatic extract, presumably due to its strong antoxidant properties, could protect the destructive effects of paraquat on rat hepatocytes.

Keywords: hepatocyte protection, levisticum officinale, oxidative stress, paraquat

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2954 FDX1, a Cuproptosis-Related Gene, Identified as a Potential Target for Human Ovarian Aging

Authors: Li-Te Lin, Chia-Jung Li, Kuan-Hao Tsui

Abstract:

Cuproptosis, a newly identified cell death mechanism, has attracted attention for its association with various diseases. However, the genetic interplay between cuproptosis and ovarian aging remains largely unexplored. This study aims to address this gap by analyzing datasets related to ovarian aging and cuproptosis. Spatial transcriptome analyses were conducted in the ovaries of both young and aged female mice to elucidate the role of FDX1. Comprehensive bioinformatics analyses, facilitated by R software, identified FDX1 as a potential cuproptosis-related gene with implications for ovarian aging. Clinical infertility biopsies were examined to validate these findings, showing consistent results in elderly infertile patients. Furthermore, pharmacogenomic analyses of ovarian cell lines explored the intricate association between FDX1 expression levels and sensitivity to specific small molecule drugs. Spatial transcriptome analyses revealed a significant reduction in FDX1 expression in aging ovaries, supported by consistent findings in biopsies from elderly infertile patients. Pharmacogenomic investigations indicated that modulating FDX1 could influence drug responses in ovarian-related therapies. This study pioneers the identification of FDX1 as a cuproptosis-related gene linked to ovarian aging. These findings not only contribute to understanding the mechanisms of ovarian aging but also position FDX1 as a potential diagnostic biomarker and therapeutic target. Further research may establish FDX1's pivotal role in advancing precision medicine and therapies for ovarian-related conditions.

Keywords: cuproptosis, FDX1, ovarian aging, biomarker

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2953 Design and Synthesis of Some Oxadiazole Bearing Benzimidazole Derivatives as Potential Epidermal Growth Factor Receptor Inhibitors

Authors: Ismail Celik, Gulgun Ayhan Kilcigil, Berna Guven, Zumra Kara, Arzu Onay-Besikci

Abstract:

Epidermal Growth Factor Receptor is the cell-surface receptor of the ErbB (erythroblastic leukemia viral oncogene homologue receptors) family of tyrosine kinases. It plays a vital role in regulating the proliferation and differentiation of cells. However, a variety of mechanisms, such as EGFR expression, mutation, and ligand-dependent receptor dimerization, are associated with the development of various activated EGFR tumors. EGFR is highly expressed in most solid tumors, including breast, head and neck cancer, non-small cell lung cancer (NSCLC), renal, ovarian, and colon cancers. Thus, specific EGFR inhibition plays one of the key roles in cancer treatment. The compounds used in the treatment as tyrosine kinase inhibitors are known to contain the benzimidazole isosterium indole, pazopanib, and axitinibin indazole rings. In addition, benzimidazoles have been shown to exhibit protein kinase inhibitory activity in addition to their different biological activities.Based on these data, it was planned and synthesized of some oxadiazole bearing benzimidazole derivatives [N-cyclohexyl-5-((2-phenyl/substitutedphenyl-1H-benzo[d]imidazole-1-yl) methyl)-1,3,4-oxadiazole-2-amine]. EGFR kinase inhibitory efficiency of the synthesized compounds was determined by comparing them with a known kinase inhibitor erlotinib in vitro, and two of the compounds bearing phenyl (19a) and 3,4-dibenzyloxyphenyl (21a) ring exhibited significant activities.

Keywords: benzimidazole, EGFR kinase inhibitory, oxadiazole, synthesis

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2952 Assessment of Isatin as Surface Recognition Group: Design, Synthesis and Anticancer Evaluation of Hydroxamates as Novel Histone Deacetylase Inhibitors

Authors: Harish Rajak, Kamlesh Raghuwanshi

Abstract:

Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.

Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking

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2951 Advertising Incentives of National Brands against Private Labels

Authors: Lu Liao

Abstract:

This paper studies the impact of private labels on the advertising incentives of national brands. The worldwide expansion of private labels over the past two decades not only transformed the choice sets of consumers but also forced manufacturers of national brands to design new marketing strategies to maintain their market positions. This paper first develops a consumer demand model that incorporates spillover effects of advertising for antacids, including private labels and finds positive spillovers of national brands’ advertising on demand for private label antacids. With the demand estimates, it provides a simulation for the equilibrium prices and advertising levels for leading national brands in a counterfactual where private labels are eliminated to quantify national brands’ advertising incentives as a response to the rise of private labels.

Keywords: advertising, private label, marketing, demand

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2950 An Enhanced Digital Forensic Model for Internet of Things Forensic

Authors: Tina Wu, Andrew Martin

Abstract:

The expansion of the Internet of Things (IoT) brings a new level of threat. Attacks on IoT are already being used by criminals to form botnets, launch Distributed Denial of Service (DDoS) and distribute malware. This opens a whole new digital forensic arena to develop forensic methodologies in order to have the capability to investigate IoT related crimes. However, existing proposed IoT forensic models are still premature requiring further improvement and validation, many lack details on the acquisition and analysis phase. This paper proposes an enhanced theoretical IoT digital forensic model focused on identifying and acquiring the main sources of evidence in a methodical way. In addition, this paper presents a theoretical acquisition framework of the different stages required in order to be capable of acquiring evidence from IoT devices.

Keywords: acquisition, Internet of Things, model, zoning

Procedia PDF Downloads 250
2949 Homogenization of a Non-Linear Problem with a Thermal Barrier

Authors: Hassan Samadi, Mustapha El Jarroudi

Abstract:

In this work, we consider the homogenization of a non-linear problem in periodic medium with two periodic connected media exchanging a heat flux throughout their common interface. The interfacial exchange coefficient λ is assumed to tend to zero or to infinity following a rate λ=λ(ε) when the size ε of the basic cell tends to zero. Three homogenized problems are determined according to some critical value depending of λ and ε. Our method is based on Γ-Convergence techniques.

Keywords: variational methods, epiconvergence, homogenization, convergence technique

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2948 Cannabidiol (CBD) Resistant Salmonella Strains Are Susceptible to Epsilon 34 Phage Tailspike Protein

Authors: Ibrahim Iddrisu, Joseph Ayariga, Junhuan Xu, Ayomide Adebanjo, Boakai K. Robertson, Michelle Samuel-Foo, Olufemi Ajayi

Abstract:

The rise of antimicrobial resistance is a global public health crisis that threatens the effective control and prevention of infections. Due to the emergence of pan drug-resistant bacteria, most antibiotics have lost their efficacy. Bacteriophages or their components are known to target bacterial cell walls, cell membranes, and lipopolysaccharides (LPS) and hydrolyze them. Bacteriophages, being the natural predators of pathogenic bacteria, are inevitably categorized as ‘human friends’, thus fulfilling the adage that ‘the enemy of my enemy is my friend’. Leveraging on their lethal capabilities against pathogenic bacteria, researchers are searching for more ways to overcome the current antibiotic resistance challenge. In this study, we expressed and purified epsilon 34 phage tail spike protein (E34 TSP) from the E34 TSP gene, then assessed the ability of this bacteriophage protein in the killing of two CBD-resistant strains of Salmonella spp. We also assessed the ability of the tail spike protein to cause bacteria membrane disruption and dehydrogenase depletion. We observed that the combined treatment of CBD-resistant strains of Salmonella with CBD and E34 TSP showed poor killing ability, whereas the mono treatment with E34 TSP showed considerably higher killing efficiency. This study demonstrates that the inhibition of the bacteria by E34 TSP was due in part to membrane disruption and dehydrogenase inactivation by the protein. The results of this work provide an interesting background to highlight the crucial role phage proteins such as E34 TSP could play in pathogenic bacterial control.

Keywords: cannabidiol, resistance, Salmonella, antimicrobials, phages

Procedia PDF Downloads 44
2947 Coal Preparation Plant:Technology Overview and New Adaptations

Authors: Amit Kumar Sinha

Abstract:

A coal preparation plant typically operates with multiple beneficiation circuits to process individual size fractions of coal obtained from mine so that the targeted overall plant efficiency in terms of yield and ash is achieved. Conventional coal beneficiation plant in India or overseas operates generally in two methods of processing; coarse beneficiation with treatment in dense medium cyclones or in baths and fines beneficiation with treatment in flotation cell. This paper seeks to address the proven application of intermediate circuit along with coarse and fines circuit in Jamadoba New Coal Preparation Plant of capacity 2 Mt/y to treat -0.5 mm+0.25 mm size particles in reflux classifier. Previously this size of particles was treated directly in Flotation cell which had operational and metallurgical limitations which will be discussed in brief in this paper. The paper also details test work results performed on the representative samples of TSL coal washeries to determine the top size of intermediate and fines circuit and discusses about the overlapping process of intermediate circuit and how it is process wise suitable to beneficiate misplaced particles from coarse circuit and fines circuit. This paper also compares the separation efficiency (Ep) of various intermediate circuit process equipment and tries to validate the use of reflux classifier over fine coal DMC or spirals. An overview of Modern coal preparation plant treating Indian coal especially Washery Grade IV coal with reference to Jamadoba New Coal Preparation Plant which was commissioned in 2018 with basis of selection of equipment and plant profile, application of reflux classifier in intermediate circuit and process design criteria is also outlined in this paper.

Keywords: intermediate circuit, overlapping process, reflux classifier

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2946 Impact of Environmental Changes on Blood Parameters in the Pelophylax ridibundus

Authors: Murat Tosunoglu, Cigdem Gul, Nurcihan Hacioglu, Nurdan Tepeova

Abstract:

Amphibian and Reptilian species are influenced by pollution and habitat destruction. Blood parameters of Amphibia species were particularly affected by the negative environmental conditions. Studied frog samples 36 clinically normal Pelophylax ridibundus individuals were captured along the Biga Stream between April–June 2014. When comparing our findings with the Turkish legislation (Water pollution control regulation), the 1. Locality of the Biga stream in terms of total coliform classified as "high quality water" (Coliform: 866.66 MPN/100 mL), while the 2. locality was a "contaminated water" (Coliform: 53266.66 MPN/100 mL). Blood samples of the live specimens were obtained in the laboratory within one day of their capture. The blood samples were taken from the etherized frogs by means of ventriculus punctures, via heparinized hematocrit capillaries. Hematological and biochemical analyses based on high quality water and contaminated water, respectively, are as follows: Red blood cell count (444210.52-426846.15 per cubic millimeter of blood), white blood cell count (4215.78-4684.61 per cubic millimeter of blood), hematocrit value (29.25-29.43 %), hemoglobin concentration (7.76-7.22 g/dl), mean corpuscular volume (637.64-719.99 fl), mean corpuscular hemoglobin (184.78-174.75 pg), mean corpuscular hemoglobin concentration (29.44-24.82 %), glucose (103.74-124.13 mg/dl), urea (87.68-81.72 mg/L), cholesterol (148.20-197.39 mg/dl), creatinine (0.29-0.28 mg/dl), uric acid (10.26-7.55 mg/L), albumin (1.13-1.39 g/dl), calcium (11.45-9.70 mg/dl), triglyceride (135.23-155.85 mg/dl), total protein (4.26-3.73 g/dl), phosphorus (6.83-17.86 mg/dl), and magnesium (0.95-1.06 mg/dl). The some hematological parameters in P. ridibundus specimens are given for the first time in this study. No water quality dependent variation was observed in clinic hematology parameters measured.

Keywords: Pelophylax ridibundus, hematological parameters, biochemistry, freshwater quality

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2945 Comparison of Anterolateral Thigh Flap with or without Acellular Dermal Matrix in Repair of Hypopharyngeal Squamous Cell Carcinoma Defect: A Retrospective Study

Authors: Yaya Gao, Bing Zhong, Yafeng Liu, Fei Chen

Abstract:

Aim: The purpose of this study was to explore the difference between acellular dermal matrix (ADM) combined with anterolateral thigh (ALT) flap and ALT flap alone. Methods: HSCC patients were treated and divided into group A (ALT) and group B (ALT+ADM) between January 2014 and December 2018. We compared and analyzed the intraoperative information and postoperative outcomes of the patients. Results: There were 21 and 17 patients in group A and group B, respectively. The operation time, blood loss, defect size and anastomotic vessel selection showed no significant difference between two groups. The postoperative complications, including wound bleeding (n=0 vs. 1, p=0.459), wound dehiscence (n=0 vs. 1, p=0.459), wound infection (n=5vs.3, p=0.709), pharyngeal fistula (n=5vs.4, p=1.000) and hypoproteinemia (n=11 vs. 12, p=0.326) were comparable between the groups. Dysphagia at 6 months (number of liquid diets=0vs. 0; number of partial tube feedings=1vs. 1; number of total tube feedings=1vs. 0, p=0.655) also showed no significant differences. However, significant differences was observed in dysphagia at 12 months (number of liquid diets=0vs. 0; number of partial tube feedings=3 vs. 1; number of total tube feedings=10vs. 1, p=0.006). Conclusion: For HSCC patients, the use of the ALT flap combined ADM, compared to ALT treatment, showed better swallowing function at 12 months. The ALT flap combined ADM may serve as a safe and feasible alternative for selected HSCC patients.

Keywords: hypopharyngeal squamous cell carcinoma, anterolateral thigh free flap, acellular dermal matrix, reconstruction, dysphagia

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2944 The Structural, Elastic, Thermal, Electronic, and Magnetic Properties of Intermetallic rmn₂ge₂ (R=CA, Y, ND)

Authors: I. Benkaddour, Y. Benkaddour, A. Benk Addour

Abstract:

The structural, elastic, Thermal, electronic, and magnetic properties of intermetallic RMn₂Ge₂ (R= Ca, Y, Nd) are investigated by density functional theory (DFT), using the full potential –linearised augmented plane wave method (FP-LAPW). In this approach, the local-density approximation (LDA) is used for the exchange-correlation (XC) potential. The equilibrium lattice constant and magnetic moment agree well with the experiment. The density of states shows that these phases are conductors, with contribution predominantly from the R and Mn d states. We have determined the elastic constants C₁₁, C₁₂, C₁₃, C₄₄, C₃₃, andC₆₆ at ambient conditions in, which have not been established neither experimentally nor theoretically. Thermal properties, including the relative expansion coefficients and the heat capacity, have been estimated using a quasi-harmonic Debye model.

Keywords: RMn₂Ge₂, intermetallic, first-principles, density of states, mechanical properties

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2943 Evaluation of Antagonistic and Aggregation Property of Probiotic Lactic Acid Bacteria Isolated from Bovine Milk

Authors: Alazar Nebyou, Sujata Pandit

Abstract:

Lactic acid bacteria (LAB) are essential ingredients in probiotic foods, intestinal microflora, and dairy products that are capable of coping up with harsh gastrointestinal tract conditions and are available in a variety of environments. The objective of this study is to evaluate the probiotic property of LAB isolated from bovine milk. Milk samples were collected from local dairy farms. Samples were obtained using sterile test tubes and transported to a laboratory in the icebox for further biochemical characterization. Preliminary physiological and biochemical identification of LAB isolates was conducted by growing on MRS agar after ten-fold serial dilution. Seven of the best isolates were selected for the evaluation of the probiotic property. The LAB isolates were checked for resistance to antibiotics and their antimicrobial activity by disc diffusion assay and agar well diffusion assay respectively. Bile salt hydrolase activity of isolates was studied by growing isolates in a BSH medium with bile salt. Cell surface property of isolates was assayed by studying their autoaggregation and coaggregation percentage with S. aerues. All isolates were found BSH positive. In addition, BCM2 and BGM1 were susceptible to all antibiotic disks except BBM1 which was resistant to all antibiotic disks. BCM1 and BGM1 had the highest autoaggregation and coaggregation potential respectively. Since all LAB isolates showed gastrointestinal tolerance and good cell surface property they could be considered as good potential probiotic candidates for treatment and probiotic starter culture preparation.

Keywords: probiotic, aggregation, lactic acid bacteria, antimicrobial activity

Procedia PDF Downloads 198
2942 A Survey on Routh-Hurwitz Stability Criterion

Authors: Mojtaba Hakimi-Moghaddam

Abstract:

Routh-Hurwitz stability criterion is a powerful approach to determine stability of linear time invariant systems. On the other hand, applying this criterion to characteristic equation of a system, whose stability or marginal stability can be determined. Although the command roots (.) of MATLAB software can be easily used to determine the roots of a polynomial, the characteristic equation of closed loop system usually includes parameters, so software cannot handle it; however, Routh-Hurwitz stability criterion results the region of parameter changes where the stability is guaranteed. Moreover, this criterion has been extended to characterize the stability of interval polynomials as well as fractional-order polynomials. Furthermore, it can help us to design stable and minimum-phase controllers. In this paper, theory and application of this criterion will be reviewed. Also, several illustrative examples are given.

Keywords: Hurwitz polynomials, Routh-Hurwitz stability criterion, continued fraction expansion, pure imaginary roots

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2941 Understanding the Role of Nitric Oxide Synthase 1 in Low-Density Lipoprotein Uptake by Macrophages and Implication in Atherosclerosis Progression

Authors: Anjali Roy, Mirza S. Baig

Abstract:

Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid rich plaque enriched with necrotic core, modified lipid accumulation, smooth muscle cells, endothelial cells, leucocytes and macrophages. Macrophage foam cells play a critical role in the occurrence and development of inflammatory atherosclerotic plaque. Foam cells are the fat-laden macrophages in the initial stage atherosclerotic lesion formation. Foam cells are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening. The mechanisms that drive atherosclerotic plaque progression remain largely unknown. Dissecting the molecular mechanism involved in process of macrophage foam cell formation will help to develop therapeutic interventions for atherosclerosis. To investigate the mechanism, we studied the role of nitric oxide synthase 1(NOS1)-mediated nitric oxide (NO) on low-density lipoprotein (LDL) uptake by bone marrow derived macrophages (BMDM). Using confocal microscopy, we found that incubation of macrophages with NOS1 inhibitor, TRIM (1-(2-Trifluoromethylphenyl) imidazole) or L-NAME (N omega-nitro-L-arginine methyl ester) prior to LDL treatment significantly reduces the LDL uptake by BMDM. Further, addition of NO donor (DEA NONOate) in NOS1 inhibitor treated macrophages recovers the LDL uptake. Our data strongly suggest that NOS1 derived NO regulates LDL uptake by macrophages and foam cell formation. Moreover, we also checked proinflammatory cytokine mRNA expression through real time PCR in BMDM treated with LDL and copper oxidized LDL (OxLDL) in presences and absences of inhibitor. Normal LDL does not evoke cytokine expression whereas OxLDL induced proinflammatory cytokine expression which significantly reduced in presences of NOS1 inhibitor. Rapid NOS-1-derived NO and its stable derivative formation act as signaling agents for inducible NOS-2 expression in endothelial cells, leading to endothelial vascular wall lining disruption and dysfunctioning. This study highlights the role of NOS1 as critical players of foam cell formation and would reveal much about the key molecular proteins involved in atherosclerosis. Thus, targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages at early stage of disease and hence dampening the atherosclerosis progression.

Keywords: atherosclerosis, NOS1, inflammation, oxidized LDL

Procedia PDF Downloads 117