Search results for: interferon alpha and beta receptor subunit 2
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1635

Search results for: interferon alpha and beta receptor subunit 2

555 Opuntia ficus-indica var. Saboten Stimulates Adipogenesis, Lipolysis, and Glucose Uptake in 3T3-L1 Adipocytes

Authors: Hye Kyung Kim, Myung-Gyou Kim, Kang-Hyun Leem

Abstract:

The prickly pear cactus (Opuntia ficus-indica) has a global distribution and has been used for medicinal benefits such as artherosclerosis, diabetes, gastritis, and hyperglycemia. The prickly pear variety Opuntia ficus-indica var. Saboten (OFS) is widely cultivated in Cheju Island, the southwestern region of Korea, and used as a functional food. The present study investigated the effects of OFS on adipogenesis, lipolysis, glucose uptake, and glucose transporter (GLUT4) expression using preadipocyte 3T3-L1 cells. Adipogenesis was determined by preadipocyte differentiation and triglyceride accumulation assessed by Oil Red O staining. Lipolysis was determined as the rate of glycerol release. Insulin-stimulated glucose uptake and GLUT4 expression were measured using fluorescent glucose analogue, 2-NBDG, and ELISA, respectively. Quantitative real-time RT-PCR was performed to investigate the effects of OFS on the mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), a regulator of adipocyte differentiation. Ethanol extracts of OFS dose-dependently enhanced adipocyte differentiation and cellular triglyceride levels indicating the enhancement of the differentiation of preadipocytes into adipocytes. Insulin-stimulated glucose uptake and GLUT4 expression were also dose-dependently increased by OFS treatment. Furthermore, OFS treatment also increased the mRNA levels of PPARγ. These effects of OFS on adipocytes suggest that OFS is potentially beneficial for type 2 diabetes by due to its enhanced glucose uptake and balanced adipogenesis and lipolysis properties.

Keywords: 3T3-L1 preadipocyte cell, adipogenesis, GLUT4, lipolysis, Opuntia ficus-indica var. Saboten, PPARγ, prickly pear cactus

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554 Relationship between Interest, Attitude and Academic Performance among N.C.E Primary Education Studies of College of Education, Azare Bauchi State

Authors: Fatima Ibrahim

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The Study assessed the relationship between interest, attitude and academic performance among N.C.E Primary Education Studies of College of Education, Azare Bauchi State. Stratified random sampling was used to select 234 respondents from N.C.E 100, 200 and 300 levels students with the total population of 552. Structured Questionnaire and students academic records were used for data collection. Four scale format was used for the respondents to indicate their degree of satisfaction on a four point scale. Four null hypothesis were formulated from research questions at tested at 0.05 level of significance. The data collected from the study were analyzed using descriptive statistics, pearson product moment correlation coefficient and independent test. The result of tested Null hypotheses revealed that: there was significant relationship between student’s interest and their academic performance since calculated p value of 0.000 is less than the 0.05 alpha level of significance at a correlation index level of .986 hence the Null hypothesis was rejected. There was significant relationship between student’s attitude and their academic performance in the study of P.E.S. Findings also revealed that majority of the students were interested in the study of P.E.S which helped them perform well. It was concluded that significant relationship exists between students interest, attitudinal academic performance among P.E.S students in College of Education Azare.

Keywords: Attitude, Academic Performance, College of Education Azare, Interest, Students

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553 Vocational and Technical Educators’ Acceptance and Use of Digital Learning Environments Beyond Working Hours: Implications for Work-Life Balance and the Role of Integration Preference

Authors: Jacinta Ifeoma Obidile

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Teachers (vocational and technical educators inclusive) use Information and Communications Technology (ICT) for tasks outside of their normal working hours. This expansion of work duties to non-work time challenges their work-life balance. However, there has been inconsistency in the results on how these relationships correlate. This, therefore, calls for further research studies to examine the moderating mechanisms of such relationships. The present study, therefore, ascertained how vocational and technical educators’ technology acceptance relates to their work-related ICT use beyond their working hours and work-life balance, as well as how their integration affects these relationships. The population of the study comprised 320 Vocational and Technical Educators from the Southeast geopolitical zone of Nigeria. Data were collected from the respondents using the structured questionnaire. The questionnaire was validated by three experts. The reliability of the study was conducted using 20 vocational and technical educators from the South who were not part of the population. The overall reliability coefficient of 0.81 was established using Cronbach’s alpha method. The data collected was analyzed using Structural equation modeling. Findings, among others, revealed that vocational and technical educators’ work-life balance was mediated by increased digital learning environment use after work hours, although reduced by social influence.

Keywords: vocational and technical educators, digital learning environment, working hours, work-life balance, integration preference

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552 Anti-inflammatory Effect of Wild Indigo (Baptisia tinctoria) Root on Raw 264.7 Cells with Stimulated Lipopolysaccharide

Authors: Akhmadjon Sultanov, Eun-Ho Lee, Hye-Jin Park, Young-Je Cho

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This study tested the anti-inflammatory effect of wild indigo (Baptisia tinctoria) root in Raw 264.7 cells. We prepared two extracts of B. tinctoria; one in water and the other in 50% ethanol. Then we evaluated the toxicities of the B. tinctoria root extracts at 10 to 100 mg mL-1 concentrations in raw 264.7 cells and observed 80% cell viability. The anti-inflammatory effect of B. tinctoria root extract in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells were observed with concentrations at 10, 30, and 50 μg mL-1. The results showed that 77.27-66.82% of nitric oxide (NO) production was inhibited by 50 μg mL-1 B. tinctoria root extract. The protein expression of Inducible NO synthase (iNOS) expression dramatically decreased by 93.14% and 52.65% in raw 264.7 cells treated with water and ethanol extracts of B. tinctoria root, respectively. Moreover, cyclooxygenase-2 (COX-2) protein expression decreased by 42.85% and 69.70% in raw 264.7 cells treated with water and ethanol extracts of B. tinctoria root, respectively. Furthermore, the mRNA expression of pro-inflammatory markers, such as tumor necrosis factor-alpha, interleukin-1β, interleukin-6, monocyte chemoattractant protein-1, and prostaglandin E synthase 2, was significantly suppressed in a concentration-dependent manner. Additionally, the B. tinctoria root extracts effectively inhibited enzymes involved in physiological activities. The B. tinctoria root extracts showed excellent anti-inflammatory effects and can be used as a functional material for biological activities.

Keywords: cytokine, macrophage, pro-inflammatory, protein expression, real-time PCR

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551 Estimation of Pressure Profile and Boundary Layer Characteristics over NACA 4412 Airfoil

Authors: Anwar Ul Haque, Waqar Asrar, Erwin Sulaeman, Jaffar S. M. Ali

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Pressure distribution data of the standard airfoils is usually used for the calibration purposes in subsonic wind tunnels. Results of such experiments are quite old and obtained by using the model in the spanwise direction. In this manuscript, pressure distribution over NACA 4412 airfoil model was presented by placing the 3D model in the lateral direction. The model is made of metal with pressure ports distributed longitudinally as well as in the lateral direction. The pressure model was attached to the floor of the tunnel with the help of the base plate to give the specified angle of attack to the model. Before the start of the experiments, the pressure tubes of the respective ports of the 128 ports pressure scanner are checked for leakage, and the losses due to the length of the pipes were also incorporated in the results for the specified pressure range. Growth rate maps of the boundary layer thickness were also plotted. It was found that with the increase in the velocity, the dynamic pressure distribution was also increased for the alpha seep. Plots of pressure distribution so obtained were overlapped with those obtained by using XFLR software, a low fidelity tool. It was found that at moderate and high angles of attack, the distribution of the pressure coefficients obtained from the experiments is high when compared with the XFLR ® results obtained along with the span of the wing. This under-prediction by XFLR ® is more obvious on the windward than on the leeward side.

Keywords: subsonic flow, boundary layer, wind tunnel, pressure testing

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550 Counselling Needs of Psychiatric Patients as Perceived by Their Medical Personnel, in Federal Neuropsychiatric Hospital, Aro, Abeokuta

Authors: F. N. Bolu-Steve, T. A. Ajiboye

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A study was carried out on the awareness of counselling needs of psychiatric patients as perceived by medical personnel in the Federal Neuropsychiatric hospital, Aro, Abeokuta, Nigeria. The respondents comprised of medical personnel of the Neuropsychiatric hospital in Aro. Purposive sampling technique was used to select the respondents. The target population of the study consisted of all medical doctors treating the psychiatric patients. A total of 200 respondents participated in the study out of which 143 were males and 57 of them were females. With their years of experience as a medical doctors, 49.5% of them have worked between 1-5 years, 30.5% of the respondents have 6-10 years’ experience while those with 16 years and above experience are 7.0%. The major counselling need of psychiatric patients as expressed by medical doctors is the need to have information about the right balance diet. The data were analyzed using percentages, mean, frequency, Analysis of Variance (ANOVA) and t-test statistical tools. The instrument used for data collection was the structured questionnaire titled “Counselling Needs of Psychiatric Patients Questionnaire” (CNPPQ). This instrument was drafted by the researchers through the review of related literature. The reliability of the instrument was established using test-retest method. A reliability index of 0.74 was obtained. Three of the hypotheses were rejected while two of them were accepted at 0.05 alpha level of significance. Based on the findings of the study, it was recommended that broad based counselling services should be provided to psychiatric patients in order to assist them to develop positive self- image and to cope with their challenges.

Keywords: counselling, needs, psychiatric, medical personnel, patients

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549 Statistical Modelling of Maximum Temperature in Rwanda Using Extreme Value Analysis

Authors: Emmanuel Iyamuremye, Edouard Singirankabo, Alexis Habineza, Yunvirusaba Nelson

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Temperature is one of the most important climatic factors for crop production. However, severe temperatures cause drought, feverish and cold spells that have various consequences for human life, agriculture, and the environment in general. It is necessary to provide reliable information related to the incidents and the probability of such extreme events occurring. In the 21st century, the world faces a huge number of threats, especially from climate change, due to global warming and environmental degradation. The rise in temperature has a direct effect on the decrease in rainfall. This has an impact on crop growth and development, which in turn decreases crop yield and quality. Countries that are heavily dependent on agriculture use to suffer a lot and need to take preventive steps to overcome these challenges. The main objective of this study is to model the statistical behaviour of extreme maximum temperature values in Rwanda. To achieve such an objective, the daily temperature data spanned the period from January 2000 to December 2017 recorded at nine weather stations collected from the Rwanda Meteorological Agency were used. The two methods, namely the block maxima (BM) method and the Peaks Over Threshold (POT), were applied to model and analyse extreme temperature. Model parameters were estimated, while the extreme temperature return periods and confidence intervals were predicted. The model fit suggests Gumbel and Beta distributions to be the most appropriate models for the annual maximum of daily temperature. The results show that the temperature will continue to increase, as shown by estimated return levels.

Keywords: climate change, global warming, extreme value theory, rwanda, temperature, generalised extreme value distribution, generalised pareto distribution

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548 Induction of HIV-1 Resistance: The New Approaches Based on Gene Modification and Stem Cell Engineering

Authors: Alieh Farshbaf

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Introduction: Current anti-retroviral drugs have some restrictions for treatment of HIV-1 infection. The efficacy of retroviral drugs is not same in different infected patients and the virus rebound from latent reservoirs after stopping them. Recently, the engineering of stem cells and gene therapy provide new approaches to eliminate some drug problems by induction of resistance to HIV-1. Literature review: Up to now, AIDS-restriction genes (ARGs) were suitable candidate for gene and cell therapies, such as cc-chemokine receptor-5 (CCR5). In this manner, CCR5 provide effective cure in Berlin and Boston patients by inducing of HIV-1 resistance with allogeneic stem cell transplantation. It is showed that Zinc Finger Nuclease (ZFN) could induce HIV-1 resistance in stem cells of infected patients by homologous recombination or non-end joining mechanism and eliminate virus loading after returning the modified cells. Then, gene modification by HIV restriction factors, as TRIM5, introduced another gene candidate for HIV by interfering in infection process. These gene modifications/editing provided by stem cell futures that improve treatment in refractory disease such as HIV-1. Conclusion: Although stem cell transplantation has some complications, but in compare to retro-viral drugs demonstrated effective cure by elimination of virus loading. On the other hand, gene therapy is cost-effective for an infected patient than retroviral drugs payment in a person life-long. The results of umbilical cord blood stem cell transplantation showed that gene and cell therapy will be applied easier than previous treatment of AIDS with high efficacy.

Keywords: stem cell, AIDS, gene modification, cell engineering

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547 A Study of Serum Beta 2-Microglobulin (β2M) and Lipid Bound Sialic Acid (LSA) Levels in Oral Carcinoma Patients

Authors: Kapoor Anurag, Sharma Pradeep, Mittal K Kailash, Kumar Ajai, Jawad Kalbe, Amit Kumar Singh

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Background: Oral squamous cell carcinoma (OSCC) is the most prevalent malignant tumour on a global scale. Limited research has been conducted on tumour markers in oral cancer, and additional evaluation is required for several tumour producers that show clinical promise. The present study aimed to find out the co-relation of β-2 Microglobulin and Lipid Bound Sialic Acid in oral carcinoma patients. Methodology: The present case-control study was carried out on 35 patients with histopathologically confirmed OSCC and 35 age-matched controls. Serum concentrations of 2-Microglobulin and Total Sialic Acid (TSA) in the participants were determined via ELISA and spectrophotometric technique, respectively. Results: The OSCC group consisted of 20 males and 15 females, with an average age of 58 years, while the control group comprised 18 males and 17 females, with an average age of 55 years. Elevated levels of β2-microglobulin (3.87±0.12) and LSA (73.57±2.42) were observed in OSCC patients compared to controls (2.25±0.18; 65.21±2.06, respectively). Further examination based on smoking status revealed a significant increase in both β2-microglobulin and LSA levels among smokers compared to non-smokers (p < 0.05). Conclusion: The study suggests a notable association between higher levels of β2-microglobulin and LSA in oral squamous cell carcinoma (OSCC) patients who smoke compared to non-smokers. This observation leads to a hypothesis that this disparity could potentially serve as a significant contributing factor to the advancement of oral cancer.

Keywords: biochemistry human cancer, human, oral carcinoma, marker

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546 Hepatoprotective Assessment of L-Ascorbate 1-(2-Hydroxyethyl)-4,6-Dimethyl-1, 2-Dihydropyrimidine-2-On Exposure to Carbon Tetrachloride

Authors: Nail Nazarov, Alexandra Vyshtakalyuk, Vyacheslav Semenov, Irina Galyametdinova, Vladimir Zobov, Vladimir Reznik

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Among hepatic pyrimidine used as a means of stimulating protein synthesis and recovery of liver cells in her damaged toxic and infectious etiology. When an experimental toxic hepatitis hepatoprotective activity detected some pyrimidine derivatives. There are literature data on oksimetiluratcila hepatoprotective effect. For analogs of pyrimidine nucleobases - drugs Methyluracilum pentoxy and hepatoprotective effect of weakly expressed. According to the American scientists broad spectrum of biological activity, including hepatoprotective properties, have a 2,4-dioxo-5-arilidenimino uracils. Influenced Xymedon medicinal preparation (1- (beta-hydroxyethyl) -4,6-dimethyl-1,2-dihydro-2-oksopirimidin) developed as a means of stimulating the regeneration of tissue revealed increased activity of microsomal oxidases human liver. In studies on the model of toxic liver damage in rats have shown hepatoprotective effect xymedon and stimulating its impact on the recovery of the liver tissue. Hepatoprotective properties of the new compound in the series of pyrimidine derivatives L-ascorbate 1-(2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropirimidine-2-one synthesized on the basis Xymedon preparation were firstly investigated on rats under the carbon tetrachloride action. It was shown the differences of biochemical parameters from the reference value and severity of structural-morphological liver violations decreased in comparison with control group under the influence of the compound injected before exposure carbon tetrachloride. Hepatoprotective properties of the investigated compound were more pronounced in comparison with Xymedon.

Keywords: hepatoprotectors, pyrimidine derivatives, toxic liver damage, xymedon

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545 Increasing Self-Efficacy of Secondary School Students in Physics Using Mentoring Enhanced Strategy

Authors: Gabriel Odeh Ankeli

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The study determined how mentoring enhanced strategy can increase self-efficacy of secondary school students in physics in education zone C of Benue State, Nigeria. The study was guided by two research questions while two hypotheses were formulated and tested at 0.05 level of significance. The design of the study was the quasi-experimental, non-randomized, pre-test and post-test control groups. The population of the study consisted of 4,064 SS two physics students in the 94 schools in Education Zone C. The sample comprised 406 SS two physics students drawn from 10 schools using multi-stage sampling technique. The research instrument adapted and used for data collection was Students Self-Efficacy Scale (SSES). The research instrument was subjected to a reliability analysis using Cronbachs Alpha which yielded a reliability co-efficient of 0.84. Data collected were analyzed using discriptive statistics of mean and standard deviation to answer the research questions while inferential statistics of Analysis of Covariance (ANCOVA) was used to test the hypotheses. The findings revealed that students who were exposed to mentoring exhibited lower self-efficacy levels (F 1,405 = 2.751, P = 0.09˃0.05) than those students who were not exposed to mentoring. There was significant difference between male and female students’ self-efficacy level (F 1,211 = 5.496, P = 0.02˂0.05). Based on these findings, it was recommended among others that longer duration of mentoring period should be encouraged when using the mentoring strategy for better enhancement of Self-efficacy of students.

Keywords: physics, self-efficacy, mentoring enhanced strategy, students

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544 Differential Proteomic Profile and Terpenoid Production in Somatic Embryos of Jatropha curcas

Authors: Anamarel Medina-Hernandez, Teresa Ponce-Noyola, Ileana Vera-Reyes, Ana C. Ramos-Valdivia

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Somatic embryos reproduce original seed characteristics and could be implemented in biotechnological studies. Jatropha curcas L. is an important plant for biodiesel production, but also is used in traditional medicine. Seeds from J. curcas are toxic because contain diterpenoids called phorbol esters, but in Mexico exist a non-toxic variety. Therefore, somatic embryos suspension cultures from non-toxic J. curcas variety were induced. In order to investigate the characteristics of somatic embryos, a differential proteomic analysis was made between pre-globular and globular stages by 2-D gel electrophoresis. 108 spots were differentially expressed (p<0.02), and 20 spots from globular somatic embryos were sequenced by MALDI-TOF-TOF mass spectrometry. A comparative analysis of terpenoids production between the two stages was made by RP-18 TLC plates. The sequenced proteins were related to energy production (68%), protein destination and storage (9%), secondary metabolism (9%), signal transduction (5%), cell structure (5%) and aminoacid metabolism (4%). Regarding terpenoid production, in pre-globular and globular somatic embryos were identified sterols and triterpenes of pharmacological interest (alpha-amyrin and betulinic acid) but also it was found compounds that were unique to each stage. The results of this work are the basis to characterize at different levels the J. curcas somatic embryos so that this system can be used efficiently in biotechnological processes.

Keywords: Jatropha curcas, proteomics, somatic embryo, terpenoids

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543 Acupoint Injection of High Concentration of Glucose Attenuates Mice Chronic Pain and Depression Comorbidity

Authors: Chanya Inprasit, Yi-Wen Lin

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Inflammation causes changes of peripheral and central nervous system properties, affecting both neuronal and non-neuronal cells, resulting in inflammatory pain. Acupoint injection (AI) was developed in the 1950s and has been widely used for relieving pain. It is an acupoint-stimulating technique that utilizes anatomically based meridians derived from Chinese medicine theory. AI has been accepted as an effective treatment and is thought to display superior results when compared to traditional acupuncture methods. However, the mechanism of AI needs to be ratified by more scientific evidence in order to support the theory and its therapeutic development. In this study, we explored the effect of AI on the comorbidity of chronic pain and depression. Mice hindpaw was injected by complete Freund’s adjuvant (CFA) to induce the condition of chronic pain. Measurements of mechanical and thermal hyperalgesia and depression-like behavior were analyzed. The results indicated a positive tendency to AI treatment. The comorbidity of chronic pain and depression was investigated with relation to transient receptor potential V1 (TRPV1) mechanism through the use of TRPV1 gene deletion. The expression of nociceptors such as voltage-gated sodium channels (Navs) or TRPV1, was significantly down-regulated by AI. The expression of inflammation-activated molecules: astrocytic marker glial fibrillary acidic protein (GFAP), the microglial marker Iba-1, S100B, and related kinases, were reversed by AI in both the peripheral and central nervous system. Taken together, these data provided a detailed molecular mechanism of AI-induced analgesia and anti-inflammatory properties. This finding may be utilized for clinical practice to treat chronic pain and depression comorbidity.

Keywords: inflammatory pain, acupoint injection, TRPV1, GFAP, S100B

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542 Evaluation of Chemopreventive Activity of Medicinal Plant, Gromwell Seed against Tumor Promoting Stage

Authors: Harukuni Tokuda, Takanari Arai, Xu FengHao, Nobutaka Suzuki

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In our continuous search for anti-tumor promoting, chemopreventive active potency from natural source material, a kind of healthy tea, Gromwell seed (Coix lachryma-jobi) ext., and including compounds Monoolein and Trilinolein have been screened using the in vitro synergistic assay indicated by inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by TPA. In assay, Gromwell seed aqueous extract and hot aqueous extract exhibited the potential inhibitory effects on EBV-EA activation without strong cytotoxicity on Raji cells. In our experimental system, the inhibitory effects of both Gromwell extracts and compounds were greater than that of beta-carotene, which is known anti-tumor promoting agent and/or chemopreventive agent. These compounds were evaluated for their in vitro inhibitory effect on EBV-EA activation induced by TPA. The percentages of the inhibition of TPA-induced EBV-EA activation for these materials were 60% and 30% at concentration 100 μg. Based on the results obtained in vitro, we studied the inhibitory effect of compounds, in an in vivo two-stage carcinogenesis test of mouse skin papilloma using DMBA as an initiator and TPA as a potential promoter. The control animals showed a 100% incidence of papilloma at 20 weeks after DMBA-TPA tumor promotion, while treatment with compounds reduced the percentage of number of tumor to 60 % after 20 weeks. Results from in vitro and in vivo studies showing chemopreventive activity against TPA promoting stage and these data support the effective potency of carcinogenic stage in clinical evaluation of integrative oncology.

Keywords: gromwell seed, medicinal plant, chemoprevention, pharmaceutical medicine

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541 Oxidosqualene Cyclase: A Novel Inhibitor

Authors: Devadrita Dey Sarkar

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Oxidosqualene cyclase is a membrane bound enzyme in which helps in the formation of steroid scaffold in higher organisms. In a highly selective cyclization reaction oxidosqualene cyclase forms LANOSTEROL with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. In humans OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. The enzyme oxidosqualene: lanosterol cyclase (OSC) represents a novel target for the treatment of hypercholesterolemia. OSC catalyzes the cyclization of the linear 2,3-monoepoxysqualene to lanosterol, the initial four-ringed sterol intermediate in the cholesterol biosynthetic pathway. OSC also catalyzes the formation of 24(S), 25-epoxycholesterol, a ligand activator of the liver X receptor. Inhibition of OSC reduces cholesterol biosynthesis and selectively enhances 24(S),25-epoxycholesterol synthesis. Through this dual mechanism, OSC inhibition decreases plasma levels of low-density lipoprotein (LDL)-cholesterol and prevents cholesterol deposition within macrophages. The recent crystallization of OSC identifies the mechanism of action for this complex enzyme, setting the stage for the design of OSC inhibitors with improved pharmacological properties for cholesterol lowering and treatment of atherosclerosis. While studying and designing the inhibitor of oxidosqulene cyclase, I worked on the pdb id of 1w6k which was the most worked on pdb id and I used several methods, techniques and softwares to identify and validate the top most molecules which could be acting as an inhibitor for oxidosqualene cyclase. Thus, by partial blockage of this enzyme, both an inhibition of lanosterol and subsequently cholesterol formation as well as a concomitant effect on HMG-CoA reductase can be achieved. Both effects complement each other and lead to an effective control of cholesterol biosynthesis. It is therefore concluded that 2,3-oxidosqualene cyclase plays a crucial role in the regulation of intracellular cholesterol homeostasis. 2,3-Oxidosqualene cyclase inhibitors offer an attractive approach for novel lipid-lowering agents.

Keywords: anticholesteraemic, crystallization, statins, homeostasis

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540 Association of Antibiotics Resistance with Efflux Pumps Genes among Multidrug-Resistant Klebsiella pneumonia Recovered from Hospital Waste Water Effluents in Eastern Cape, South Africa

Authors: Okafor Joan, Nwodo Uchechukwu

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Klebsiella pneumoniae (K. pneumoniae) is a significant pathogen responsible for opportunistic and nosocomial infection. One of the most significant antibiotic resistance mechanisms in K. pneumoniae isolates is efflux pumps. Our current study identified efflux genes (AcrAB, OqxAB, MacAB, and TolC) and regulatory genes (RamR and RarA) in multidrug-resistant (MDR) K. pneumoniae isolated from hospital effluents and investigated their relationship with antibiotic resistance. The sum of 145 K. pneumoniae isolates was established by PCR and screened for antibiotic susceptibility. PCR detected efflux pump genes, and their link with antibiotic resistance was statistically examined. However, 120 (83%) of the confirmed isolated were multidrug-resistant, with the largest percentage of resistance to ampicillin (88.3%) and the weakest rate of resistance to imipenem (5.5%). Resistance to the other antibiotics ranged from 11% to 76.6%. Molecular distribution tests show that AcrA, AcrB, MacA, oqxB oqxA, TolC, MacB were detected in 96.7%, 85%, 76.7%, 70.8%, 55.8%, 39.1%, and 29.1% respectively. However, 14.3% of the isolates harboured all seven genes screened. Efflux pump system AcrAB (83.2%) was the most commonly detected in K. pneumonia isolated across all the antibiotics class-tested. In addition, the frequencies of RamR and RarA were 46.2% and 31.4%, respectively. AcrAB and OqxAB efflux pump genes were significantly associated with fluoroquinolone, beta-lactam, carbapenem, and tetracycline resistance (p<0.05). The high rate of efflux genes in this study demonstrated that this resistance mechanism is the dominant way in K. pneumoniae isolates. Appropriate treatment must be used to reduce and tackle the burden of resistant Klebsiella pneumonia in hospital wastewater effluents.

Keywords: Klebsiella pneumonia, efflux pumps, regulatory genes, multidrug-resistant, hospital, PCR

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539 Wild Rice (Zizania sp.): A Potential Source for Functional Foods and Nutraceuticals

Authors: Farooq Anwar, Gokhan Zengin, Khalid M. Alkharfy

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Wild rice (Zizania sp.) is an annual cross-pollinated, emergent, aquatic grass that mainly grows naturally in the Great Lakes region of the North America. The nutritional quality attributes of wild rice are superior to the conventional brown rice (Oryza sativa L.) in terms of higher contents of important minerals (especially phosphorous, potassium, magnesium and calcium), B-complex vitamins, vitamin E and amino acids. In some parts of the world, wild rice is valued as a primary food source. The lipids content of wild rice is reported to be low in the range of 0.7 and 1.1%, however, the lipids are recognized as a rich source of polyunsaturated fatty acids (including linoleic and α-linolenic acid) and phytosterols in addition to containing reasonably good amount of tocols. Besides, wild rice is reported to contain an appreciable amount of high-value compounds such as phenolics with antioxidant properties. Presence of such nutritional bioactives contributes towards medicinal benefits and multiple biological activities of this specialty rice. The present lecture is mainly designed to focus on the detailed nutritional attributes, profile of high-value bioactive components and pharmaceutical/biological activities of wild rice leading to exploring functional food and nutraceutical potential of this food commodity.

Keywords: alpha-linolenic acid, phenolics, phytosterols, tocols, wild rice lipids

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538 Investigation of the Effect of Teaching Thinking and Research Lesson by Cooperative and Traditional Methods on Creativity of Sixth Grade Students

Authors: Faroogh Khakzad, Marzieh Dehghani, Elahe Hejazi

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The present study investigates the effect of teaching a Thinking and Research lesson by cooperative and traditional methods on the creativity of sixth-grade students in Piranshahr province. The statistical society includes all the sixth-grade students of Piranshahr province. The sample of this studytable was selected by available sampling from among male elementary schools of Piranshahr. They were randomly assigned into two groups of cooperative teaching method and traditional teaching method. The design of the study is quasi-experimental with a control group. In this study, to assess students’ creativity, Abedi’s creativity questionnaire was used. Based on Cronbach’s alpha coefficient, the reliability of the factor flow was 0.74, innovation was 0.61, flexibility was 0.63, and expansion was 0.68. To analyze the data, t-test, univariate and multivariate covariance analysis were used for evaluation of the difference of means and the pretest and posttest scores. The findings of the research showed that cooperative teaching method does not significantly increase creativity (p > 0.05). Moreover, cooperative teaching method was found to have significant effect on flow factor (p < 0.05), but in innovation and expansion factors no significant effect was observed (p < 0.05).

Keywords: cooperative teaching method, traditional teaching method, creativity, flow, innovation, flexibility, expansion, thinking and research lesson

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537 Design, Synthesis and Pharmacological Investigation of Novel 2-Phenazinamine Derivatives as a Mutant BCR-ABL (T315I) Inhibitor

Authors: Gajanan M. Sonwane

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Nowadays, the entire pharmaceutical industry is facing the challenge of increasing efficiency and innovation. The major hurdles are the growing cost of research and development and a concurrent stagnating number of new chemical entities (NCEs). Hence, the challenge is to select the most druggable targets and to search the equivalent drug-like compounds, which also possess specific pharmacokinetic and toxicological properties that allow them to be developed as drugs. The present research work includes the studies of developing new anticancer heterocycles by using molecular modeling techniques. The heterocycles synthesized through such methodology are much effective as various physicochemical parameters have been already studied and the structure has been optimized for its best fit in the receptor. Hence, on the basis of the literature survey and considering the need to develop newer anticancer agents, new phenazinamine derivatives were designed by subjecting the nucleus to molecular modeling, viz., GQSAR analysis and docking studies. Simultaneously, these designed derivatives were subjected to in silico prediction of biological activity through PASS studies and then in silico toxicity risk assessment studies. In PASS studies, it was found that all the derivatives exhibited a good spectrum of biological activities confirming its anticancer potential. The toxicity risk assessment studies revealed that all the derivatives obey Lipinski’s rule. Amongst these series, compounds 4c, 5b and 6c were found to possess logP and drug-likeness values comparable with the standard Imatinib (used for anticancer activity studies) and also with the standard drug methotrexate (used for antimitotic activity studies). One of the most notable mutations is the threonine to isoleucine mutation at codon 315 (T315I), which is known to be resistant to all currently available TKI. Enzyme assay planned for confirmation of target selective activity.

Keywords: drug design, tyrosine kinases, anticancer, Phenazinamine

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536 Site-Specific Delivery of Hybrid Upconversion Nanoparticles for Photo-Activated Multimodal Therapies of Glioblastoma

Authors: Yuan-Chung Tsai, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu

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In order to enhance the photodynamic/photothermal therapeutic efficacy on glioblastoma, the functionized upconversion nanoparticles with the capability of converting the deep tissue penetrating near-infrared light into visible wavelength for activating photochemical reaction were developed. The drug-loaded nanoparticles (NPs) were obtained from the self-assembly of oleic acid-coated upconversion nanoparticles along with maleimide-conjugated poly(ethylene glycol)-cholesterol (Mal-PEG-Chol), as the NP stabilizer, and hydrophobic photosensitizers, IR-780 (for photothermal therapy, PTT) and mTHPC (for photodynamic therapy, PDT), in aqueous phase. Both the IR-780 and mTHPC were loaded into the hydrophobic domains within NPs via hydrophobic association. The peptide targeting ligand, angiopep-2, was further conjugated with the maleimide groups at the end of PEG adducts on the NP surfaces, enabling the affinity coupling with the low-density lipoprotein receptor-related protein-1 of tumor endothelial cells and malignant astrocytes. The drug-loaded NPs with the size of ca 80 nm in diameter exhibit a good colloidal stability in physiological conditions. The in vitro data demonstrate the successful targeting delivery of drug-loaded NPs toward the ALTS1C1 cells (murine astrocytoma cells) and the pronounced cytotoxicity elicited by combinational effect of PDT and PTT. The in vivo results show the promising brain orthotopic tumor targeting of drug-loaded NPs and sound efficacy for brain tumor dual-modality treatment. This work shows great potential for improving photodynamic/photothermal therapeutic efficacy of brain cancer.

Keywords: drug delivery, orthotopic brain tumor, photodynamic/photothermal therapies, upconversion nanoparticles

Procedia PDF Downloads 189
535 Downside Risk Analysis of the Nigerian Stock Market: A Value at Risk Approach

Authors: Godwin Chigozie Okpara

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This paper using standard GARCH, EGARCH, and TARCH models on day of the week return series (of 246 days) from the Nigerian Stock market estimated the model variants’ VaR. An asymmetric return distribution and fat-tail phenomenon in financial time series were considered by estimating the models with normal, student t and generalized error distributions. The analysis based on Akaike Information Criterion suggests that the EGARCH model with student t innovation distribution can furnish more accurate estimate of VaR. In the light of this, we apply the likelihood ratio tests of proportional failure rates to VaR derived from EGARCH model in order to determine the short and long positions VaR performances. The result shows that as alpha ranges from 0.05 to 0.005 for short positions, the failure rate significantly exceeds the prescribed quintiles while it however shows no significant difference between the failure rate and the prescribed quantiles for long positions. This suggests that investors and portfolio managers in the Nigeria stock market have long trading position or can buy assets with concern on when the asset prices will fall. Precisely, the VaR estimates for the long position range from -4.7% for 95 percent confidence level to -10.3% for 99.5 percent confidence level.

Keywords: downside risk, value-at-risk, failure rate, kupiec LR tests, GARCH models

Procedia PDF Downloads 438
534 Factors Impact Satisfaction and Continuance Intention to Use Facebook

Authors: Bataineh Abdallah, Alabdallah Ghaith, Alkharabshe Abdalhameed

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Social media is an umbrella term for different types of online communication channels. The most prominent forms can be divided into four categories: Collaborative projects (e.g. Wikipedia, comparison-shopping sites), blogs (e.g. Twitter), content communities (e.g. Youtube), social networking sites (e.g. Facebook) social media allow consumers to share their opinions, criticisms and suggestions in public. Facebook launched in 2004, initially targeted college students and later started including everyone has become the most popular sites amongst the young generation for connecting with friends and relatives and for the communication of ideas. In 2013 Facebook penetration rate reached 41.4% of the population making it the most popular social networking site in Jordan. Accordingly, the purpose of this research is to examine the impact of perceived usefulness, perceived ease of use, perceived trust, perceived enjoyment and subjective norms on users' satisfaction and continuance intention to use Facebook in Jordan. Using a structured questionnaire, the primary data was collected from 584 users who have an active Facebook accounts. Multiple regression analysis was employed to test the research model and hypotheses. The research findings indicate that perceived usefulness, perceived ease of use, perceived trust, perceived enjoyment, and subjective norms have a positive and significant effect on users' satisfaction and continuance intention to use Facebook. The findings also indicated that the strongest predictors, based on beta values, on both users' satisfaction and continuance intention to use Facebook is subjective norms and respectively, perceived enjoyment, perceived usefulness, perceived ease of us, and perceived trust. Research results, recommendations, and future research opportunities are also discussed.

Keywords: perceived usefulness, perceived ease of use, perceived trust, perceived enjoyment, perceived subjective norms, users' satisfaction, continuance intention, Facebook

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533 Computational Approach for Grp78–Nf-ΚB Binding Interactions in the Context of Neuroprotective Pathway in Brain Injuries

Authors: Janneth Gonzalez, Marco Avila, George Barreto

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GRP78 participates in multiple functions in the cell during normal and pathological conditions, controlling calcium homeostasis, protein folding and unfolded protein response. GRP78 is located in the endoplasmic reticulum, but it can change its location under stress, hypoxic and apoptotic conditions. NF-κB represents the keystone of the inflammatory process and regulates the transcription of several genes related with apoptosis, differentiation, and cell growth. The possible relationship between GRP78-NF-κB could support and explain several mechanisms that may regulate a variety of cell functions, especially following brain injuries. Although several reports show interactions between NF-κB and heat shock proteins family members, there is a lack of information on how GRP78 may be interacting with NF-κB, and possibly regulating its downstream activation. Therefore, we assessed the computational predictions of the GRP78 (Chain A) and NF-κB complex (IkB alpha and p65) protein-protein interactions. The interaction interface of the docking model showed that the amino acids ASN 47, GLU 215, GLY 403 of GRP78 and THR 54, ASN 182 and HIS 184 of NF-κB are key residues involved in the docking. The electrostatic field between GRP78-NF-κB interfaces and molecular dynamic simulations support the possible interaction between the proteins. In conclusion, this work shed some light in the possible GRP78-NF-κB complex indicating key residues in this crosstalk, which may be used as an input for better drug design strategy targeting NF-κB downstream signaling as a new therapeutic approach following brain injuries.

Keywords: computational biology, protein interactions, Grp78, bioinformatics, molecular dynamics

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532 Entry Inhibitors Are Less Effective at Preventing Cell-Associated HIV-2 Infection than HIV-1

Authors: A. R. Diniz, P. Borrego, I. Bártolo, N. Taveira

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Cell-to-cell transmission plays a critical role in the spread of HIV-1 infection in vitro and in vivo. Inhibition of HIV-1 cell-associated infection by antiretroviral drugs and neutralizing antibodies (NAbs) is more difficult compared to cell-free infection. Limited data exists on cell-associated infection by HIV-2 and its inhibition. In this work, we determined the ability of entry inhibitors to inhibit HIV-1 and HIV-2 cell-to cell fusion as a proxy to cell-associated infection. We developed a method in which Hela-CD4-cells are first transfected with a Tat expressing plasmid (pcDNA3.1+/Tat101) and infected with recombinant vaccinia viruses expressing either the HIV-1 (vPE16: from isolate HTLV-IIIB, clone BH8, X4 tropism) or HIV-2 (vSC50: from HIV-2SBL/ISY, R5 and X4 tropism) envelope glycoproteins (M.O.I.=1 PFU/cell).These cells are added to TZM-bl cells. When cell-to-cell fusion (syncytia) occurs the Tat protein diffuses to the TZM-bl cells activating the expression of a reporter gene (luciferase). We tested several entry inhibitors including the fusion inhibitors T1249, T20 and P3, the CCR5 antagonists MVC and TAK-779, the CXCR4 antagonist AMD3100 and several HIV-2 neutralizing antibodies (Nabs). All compounds inhibited HIV-1 and HIV-2 cell fusion albeit to different levels. Maximum percentage of HIV-2 inhibition (MPI) was higher for fusion inhibitors (T1249- 99.8%; P3- 95%, T20-90%) followed by co-receptor antagonists (MVC- 63%; TAK-779- 55%; AMD3100- 45%). NAbs from HIV-2 infected patients did not prevent cell fusion up to the tested concentration of 4μg/ml. As for HIV-1, MPI reached 100% with TAK-779 and T1249. For the other antivirals, MPIs were: P3-79%; T20-75%; AMD3100-61%; MVC-65%.These results are consistent with published data. Maraviroc had the lowest IC50 both for HIV-2 and HIV-1 (IC50 HIV-2= 0.06 μM; HIV-1=0.0076μM). Highest IC50 were observed with T20 for HIV-2 (3.86μM) and with TAK-779 for HIV-1 (12.64μM). Overall, our results show that entry inhibitors in clinical use are less effective at preventing Env mediated cell-to-cell-fusion in HIV-2 than in HIV-1 which suggests that cell-associated HIV-2 infection will be more difficult to inhibit compared to HIV-1. The method described here will be useful to screen for new HIV entry inhibitors.

Keywords: cell-to-cell fusion, entry inhibitors, HIV, NAbs, vaccinia virus

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531 Changes on Some Physical and Chemical Properties of Red Beetroot Juice during Ultrasound Pretreatment

Authors: Serdal Sabanci, Mutlu Çevik, Derya Tezcan, Cansu Çelebi, Filiz Içier

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Ultrasound is defined as sound waves having frequencies higher than 20 kHz, which is greater than the limits of the human hearing range. In recent years, ultrasonic treatment is an emerging technology being used increasingly in the food industry. It is applied as an alternative technique for different purposes such as microbial and enzyme inactivation, extraction, drying, filtration, crystallization, degas, cutting etc. Red beetroot (Beta vulgaris L.) is a root vegetable which is rich in mineral components, folic acid, dietary fiber, anthocyanin pigments. In this study, the application of low frequency high intensity ultrasound to the red beetroot slices and red beetroot juice for different treatment times (0, 5, 10, 15, 20 min) was investigated. Ultrasonicated red beetroot slices were also squeezed immediately. Changes on colour, betanin, pH and titratable acidity properties of red beetroot juices (the ultrasonicated juice (UJ) and the juice from ultrasonicated slices (JUS)) were determined. Although there was no significant difference statistically in the changes of color value of JUS samples due to ultrasound application (p>0.05), the color properties of UJ samples ultrasonicated for low durations were statistically different from raw material (p<0.05). The difference between color values of UJ and raw material disappeared (p>0.05) as the ultrasonication duration increased. The application of ultrasound to red beet root slices adversely affected and decreased the betanin content of JUS samples. On the other hand, the betanin content of UJ samples increased as the ultrasonication duration increased. Ultrasound treatment did not affect pH and titratable acidity of red beetroot juices statistically (p>0.05). The results suggest that ultrasound technology is the simple and economical technique which may successfully be employed for the processing of red beetroot juice with improved color and betanin quality. However, further investigation is still needed to confirm this.

Keywords: red beetroot, ultrasound, color, betanin

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530 Depressant Effects of 2-PMPA through Reduction of p-CREB (Ser133) and mGluR5 Level in Prefrontal Cortex of C57BL/6 Mice

Authors: Sang-Sun Yoon, Yea-Hyun Leem, Sangmee Ahn Jo

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The N-acetylated-alpha-linked-acidic (NAAG) peptidase inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA) has demonstrated to be neuroprotective against glutamate-mediated neuron degeneration and neurological disorders such as ischemia. Several studies have demonstrated impaired psychiatric function by altered glutamate carboxypeptidase II expression, although 2-PMPA has not yet been studied. Thus, we investigated effect of 2-PMPA on depressive-like phenotype using C57BL/6 mice. Treatment of 2-PMPA (10 mg/kg for 6 days/daily, ip injection) on C57BL/6 naïve mice showed depressive-like symptoms such as decreased social preference, but did not affect the immobility measured by tail suspension test. Reduction of phosphorylated cAMP-responsive element binding (p-CREB) known as a representative marker of depressive-like behavior was observed in layer 1 and piriform cortex subregions of the prefrontal cortex of 2-PMPA-treated mice. The immunoreactivity of metabotropic glutamate receptors 5 (mGluR5) that mediate phosphorylation of CREB was also decreased in layer 1 and piriform cortex subregions of the prefrontal cortex of 2-PMPA injected mice. Thus, our results suggest that dysregulation of the GCPII or NAAG by 2-PMPA treatment is likely to be associated with pathogenesis of depression and further studies are needed to understand whether the reduced NAAG level or enhanced glutamate level in the brain is involved in this response.

Keywords: depression, GCPII, 2-PMPA, p-CREB, mGluR5

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529 Indoor Radon Concentrations in the High Levels of Uranium Deposit of Phanom and Ko Pha-Ngan Districts, Surat Thani Province, Thailand

Authors: Kanokkan Titipornpun, Somphorn Sriarpanon, Apinun Titipornpun, Jan Gimsa, Tripob Bhongsuwan, Noodchanath Kongchouy

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The Phanom and Ko Pha-ngan districts of Surat Thani province are known for their high atmospheric radon concentrations from different sources. While Phanom district is located in an active fault zone, the main radon source in Ko Pha-ngan district is the high amounts of equivalent uranium in the ground surface. Survey measurements of the indoor radon concentrations have been carried out in 105 dwellings and 93 workplaces, using CR-39 detectors that were exposed to indoor radon for forty days. Alpha tracks were made visible by chemical etching and counted manually under an optical microscope. The indoor radon concentrations in the two districts were found to vary between 9 and 63 Bq m-3 (Phanom) and 12 and 645 Bq m-3 (Ko Pha-ngan). The geometric mean radon concentration in Ko Pha-ngan district (51±2 Bq m-3) was significantly higher than in the Phanom district (26±1 Bq m-3) at a significance level of p<0.05 (t-test for independent samples). Nevertheless, only in two dwellings (1%), located in Ko Pha-ngan district, radon concentrations (177 and 645 Bq m-3) were found to exceed the limit recommended by the US EPA of 148 Bq m-3. The two houses are probably located near to radon sources which, in combination with low air convection, led to increased indoor levels of radon. Our study also shows that the geometric mean radon concentration was higher in workplaces than in dwellings (0.05 significance level) in both districts.

Keywords: indoor radon, CR-39 detector, active fault zone, equivalent uranium

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528 Proposing an Optimal Pattern for Evaluating the Performance of the Staff Management of the Water and Sewage Organization in Western Azerbaijan Province, Iran

Authors: Tohid Eskandarzadeh, Nader Bahlouli, Turaj Behnam, Azra Jafarzadeh

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The purpose of the study reported in this paper was to propose an optimal pattern to evaluate the staff management performance of the water and sewage organization. The performance prism-model was used to evaluate the following significant dimensions of performance: organizational strategies, organizational processes, organization capabilities, stakeholders’ partnership and satisfaction. In the present study, a standard, valid and reliable questionnaire was used to obtain data about the five dimensions of the performance prism model. 169 sample respondents were used for responding the questionnaire who were selected from the staff of water and waste-water organization in western Azerbaijan, Iran. Also, Alpha coefficient was used to check the reliability of the data-collection instrument which was measured to be beyond 0.7. The obtained data were statistically analyzed by means of SPSS version 18. The results obtained from the data analysis indicated that the performance of the staff management of the water and waste-water organization in western Azerbaijan was acceptable in terms of organizational strategies, organizational process, stakeholders’ partnership and satisfaction. Nevertheless, it was found that the performance of the staff management with respect to organizational abilities was average. Indeed, the researchers drew the conclusion that the current performance of the staff management in this organization in western Azerbaijan was less than ideal performance.

Keywords: performance evaluation, performance prism model, water, waste-water organization

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527 Evaluation of Anticonvulsant and Sedative-Hypnotic Activities of Novel 2-Fluorobenzyloxy 4,6- Diphenylpyrimidin-2-Ol Derivatives in Mice

Authors: Golnar Hasheminasab, Mehrdad Faizi, Mona Khoramjouy

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Introduction: Benzodiazepines (BZDs) have pharmacological effects, including anxiolytic, sedative-hypnotic, anticonvulsant, and muscle relaxant properties. However, they have adverse effects such as interaction with alcohol, ataxia, impaired learning, and psychological and physical dependence. According to the structure of zolpidem and on the basis of the structure-activity relationship of BZD receptor ligands, six novel derivatives of 2-fluorobenzyloxy 4,6- diphenylpyramidin-2-ol have been synthesized. We studied the hypnotic, sedative, and anticonvulsant effects of the novel compounds. Method: In this study, we used male mice (18 to 25 g). All the substances were injected intraperitoneally. The hypnotic effect of the compounds was examined by pentobarbital induced sleeping test. The locomotor activities and sedative effects of the novel compounds were evaluated by open field and loss of righting reflex test, respectively. The anticonvulsant effects of the novel compounds were assessed by PTZ and MES tests. Results: In the pentobarbital induced sleeping and open field tests, compound 4-(2-((2-fluorobenzyl)oxy)phenyl)-6-(p-tolyl) pyrimidine-2-ol with ED50=14.20 mg/kg and ED50=47.88 mg/kg, respectively, was the most effective compound. None of the novel compounds showed a significant anticonvulsant effect in the PTZ test. In MES test, compound 4-(2-((2-fluorobenzyl)oxy)phenyl)-6-(p-tolyl)pyrimidine-2-ol with ED50=12.92 mg/kg was the most effective compound. Flumazenil blocked the sedation and hypnosis of all the compounds. Conclusion: All of the novel derivatives showed significant sedative-hypnotic activities and caused the reduction of locomotor activities. The results show that the methyl lipophilic substitutes on the phenyl ring of 4,6-diphenylpyramidin-2-ol derivatives can increase the sedative and hypnotic effects of the derivatives. Flumazenil antagonized the sedative, and the hypnotic effects of the compounds indicate that BZD receptors are involved in the effects.

Keywords: BZD, sedative, hyptonic, anticonvulsant, zolpidem, MES, PTZ, benzodiazepine, locomotor activities, pentobarbital induced sleeping tests

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526 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 271