Search results for: protein kinase C alpha
1808 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients
Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas
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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib
Procedia PDF Downloads 2061807 Optical and Dielectric Properties of Self-Assembled 0D Hybrid Organic-Inorganic Insulator
Authors: S. Kassou, R. El Mrabet, A. Belaaraj, P. Guionneau, N. Hadi, T. Lamcharfi
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The organic–inorganic hybrid perovskite-like [C6H5C2H4NH3]2ZnCl4 (PEA-ZnCl4) was synthesized by saturated solutions method. X-ray powder diffraction, Raman spectroscopy, UV-visible transmittance, and capacitance meter measurements have been used to characterize the structure, the functional groups, the optical parameters, and the dielectric constants of the material. The material has a layered structure. The optical transmittance (T %) was recorded and applied to deduce the absorption coefficient (α) and optical band gap (Eg). The hybrid shows an insulator character with a direct band gap about 4.46 eV, and presents high dielectric constants up to a frequency of about 105 Hz, which suggests a ferroelectric behavior. The reported optical and dielectric properties can help to understand the fundamental properties of perovskite materials and also to be used for optimizing or designing new devices.Keywords: dielectric constants, optical band gap (eg), optical parameters, Raman spectroscopy, self-assembly organic inorganic hybrid
Procedia PDF Downloads 4041806 Eudesmane-Type Sesquiterpenes from Laggera alata Inhibiting Angiogenesis
Authors: Liang Ning, Chung Hau Yin
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Angiogenesis is the process of new blood vessel development. It has been recognized as a therapeutic target for blocking cancer growth four decades ago. Vascular sprouting is initiated by pro-angiogenic factors. Vascular endothelial cell growth factor (VEGF) plays a central role in angiogenic initiation, many patients with cancer or ocular neovascularization have been benefited from anti-VEGF therapy. Emerging approaches impacting in the later stages of vessel remodeling and maturation are expected to improve clinical efficacy. TIE receptor as well as the corresponding angiopoietin ligands, were identified as another endothelial cell specific receptor tyrosine kinase signaling system. Much efforts were made to reduce the activity of angiopoietin-TIE receptor axis. Two eudesmane-type sesquiterpenes from laggera alata, namely, 15-dihydrocostic acid and ilicic acid were found with strong anti-angiogenic properties in zebrafish model. Meanwhile, the mRNA expression levels of VEGFR2 and TIE2 pathway related genes were down-regulated in the sesquiterpenes treated zebrafish embryos. Besides, in human umbilical vein endothelial cells (HUVECs), the sesquiterpenes have the ability to inhibit VEGF-induced HUVECs proliferation and migration at non-toxic concentration. Moreover, angiopoietin-2 induced TIE2 phosphorylation was inhibited by the sesquiterpenes, the inhibitory effect was detected in angiopoietin-1 induced HUVECs proliferation as well. Thus, we hypothesized the anti-angiogenic activity of the compounds may via the inhibition of VEGF and TIE2 related pathways. How the compounds come into play as the pathways inhibitors need to be evaluated in the future.Keywords: Laggera alata, eudesmane-type sesquiterpene, anti-angiogenesis, VEGF, angiopoietin, TIE2
Procedia PDF Downloads 2101805 Anticancer and Anti-Apoptotic Potential of Tridham and 1,2,3,4,6-Penta-O-Galloyl-β-D-Glucose in MCF-7 Breast Cancer Cell Line
Authors: R. Stalin, D. Karthick, H. Haseena Banu, T. P. Sachidanandam, P. Shanthi
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Background: Breast cancer is emerging as one of the leading cause of cancer related deaths and hence there arises the need to look out for drugs which are more targets specific with minimal side effects. In recent times, there is a shift towards alternative medicine due to low cost and less side effects. Siddha system of medicine is one the oldest system of medicine practiced against various ailments. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio (TD) and its anticancer potential is evaluated in terms of induction of apoptosis. Objective: The present study was designed to investigate the anti proliferative effect of TD and 1,2,3,4,6-penta-O-galloyl-b-D-glucose (PGG), a pure compound isolated from TD on human mammary carcinoma cell line (MCF-7). Materials and Methods: Cell viability was studied using MTT analysis and trypan blue staining. Mitochondrial membrane potential was studied using DAPI staining. The protein and mRNA expressions of pro-apoptotic and anti- apoptotic markers namely Bax, Bad, Bcl-2 and caspases were also assessed by Western Blotting and RT PCR. Results: Viability studies of TD and PGG treated MCF-7 cells showed an inhibition in cell growth in time and dose dependent manner. The alteration in mitochondrial membrane potential was restored through treatment with TD and PGG which was confirmed by DAPI staining. The protein and mRNA expression of pro-apoptotic markers was found to be significantly increased in TD and PGG treated cells with a concomitant decrease in anti-apoptotic markers. Conclusion: The results of the study suggest that TD and PGG exhibit their anticancer effect through its membrane stabilizing property and activation of apoptotic cascade in MCF-7 cells.Keywords: apoptosis, mammary carcinoma, MCF-7, penta galloyl glucose, Tridham
Procedia PDF Downloads 3131804 Authentication and Traceability of Meat Products from South Indian Market by Species-Specific Polymerase Chain Reaction
Authors: J. U. Santhosh Kumar, V. Krishna, Sebin Sebastian, G. S. Seethapathy, G. Ravikanth, R. Uma Shaanker
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Food is one of the basic needs of human beings. It requires the normal function of the body part and a healthy growth. Recently, food adulteration increases day by day to increase the quantity and make more benefit. Animal source foods can provide a variety of micronutrients that are difficult to obtain in adequate quantities from plant source foods alone. Particularly in the meat industry, products from animals are susceptible targets for fraudulent labeling due to the economic profit that results from selling cheaper meat as meat from more profitable and desirable species. This work presents an overview of the main PCR-based techniques applied to date to verify the authenticity of beef meat and meat products from beef species. We were analyzed 25 market beef samples in South India. We examined PCR methods based on the sequence of the cytochrome b gene for source species identification. We found all sample were sold as beef meat as Bos Taurus. However, interestingly Male meats are more valuable high price compare to female meat, due to this reason most of the markets samples are susceptible. We were used sex determination gene of cattle like TSPY(Y-encoded, testis-specific protein TSPY is a Y-specific gene). TSPY homologs exist in several mammalian species, including humans, horses, and cattle. This gene is Y coded testis protein genes, which only amplify the male. We used multiple PCR products form species-specific “fingerprints” on gel electrophoresis, which may be useful for meat authentication. Amplicons were obtained only by the Cattle -specific PCR. We found 13 market meat samples sold as female beef samples. These results suggest that the species-specific PCR methods established in this study would be useful for simple and easy detection of adulteration of meat products.Keywords: authentication, meat products, species-specific, TSPY
Procedia PDF Downloads 3761803 Study of Effective Factors Influencing the Pragmatics of Knowledge Management in Iranian Oil Terminals Company
Authors: Ali Asghar Asad Sangabi, Afsaneh Aeen, Mohammad Behroozi
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Knowledge management is vital in today's world as one of the most valuable intangible assets regarded by companies. This study aimed to identify factors that affect the application of knowledge management in the Iranian Oil Terminals Company in 2022. In this study, 12 of the factors affecting the application of knowledge management have been studied, and implement practical solutions, and reuse has been studied. This study is descriptive data from the questionnaire factors affecting knowledge management application used by Cronbach's Coefficient Alpha equal to 0.85. The population of this study consisted of 1500 IOTC employees. The sample is determined by the Cochran formula sample; the results of this study showed that between the application of knowledge management and factors, there is a significant correlation. Among the factors that have been studied, valuable teamwork and organizational culture were the most effective, and the infrastructure of information systems had the least impact on Knowledge management.Keywords: knowledge management, knowledge-based organization, Iranian Oil Terminals
Procedia PDF Downloads 1601802 Development of Low Calorie Jelly with Increased Content of Natural Compounds from Superfoods with No Added Sugar
Authors: Liana C. Salanță, Maria Tofană, Carmen R. Pop, Vlad Mureșan
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The landscape of functional food is expanding very fast, due to the consumer interest for healthy natural products. Consumers nowadays demand healthy products that impart phytonutrients to encourage good health and well-being, prevent diseases, without sacrificing taste and texture. Candies are foodstuffs appreciated by all category of consumers. They are available in a range variety of forms (jellies, marshmallows, caramels, lollipops, etc.). Jelly is characterized by a gummy and chewy texture typically conferred by a hydrocolloid (gelatin, pectin). The purpose of this research was to obtain hypocaloric jelly (no added sugar) enriched with protein powder from acai, chia seeds and hemp, which are considered superfood. Peach and raspberry juice were used for obtaining functional jelly, due to the specific flavour, natural carbohydrate, natural pigments and vitamins (C, B1, PP, etc). Instead of classic hydrocolloids used in Romania for the industry of jelly, agar-agar was used in this study, due to its properties. Agar-agar is able to form gels in the aqueous medium, stronger than other gel-forming agents. High sugar concentrations or an acid environment (as is necessary with pectins) are not needed. In addition to its gelation properties, Agar-agar is considered to have important nutritional benefits, high content of fibre and has low calories. Six prototypes of jellies were obtained and evaluated by physicochemical, microbiological and sensorial analysis. For the textural profile analysis, the Brookfield CT3 Texture Analyzer, equipped with a 10kg load cell, was used. The results revealed that hypocaloric jelly can serve as a good source of bioactive compounds in the diet. The jelly is a convenient way of delivering potential health benefits of protein powder and agar-agar to a wide range of consumers.Keywords: agar-agar, functional food, hypocaloric jelly, superfoods
Procedia PDF Downloads 1291801 Characteristics of Smoked Edible Film Made from Myofibril, Collagen and Carrageenan
Authors: Roike Iwan Montolalu, Henny Adeleida Dien, Feny Mentang, Kristhina P. Rahael, Tomy Moga, Ayub Meko, Siegfried Berhimpon
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In the last 20 years, packaging materials derived from petrochemicals polymers were widely used as packaging materials. This due to various advantages such as flexible, strong, transparent, and the price is relatively cheap. However, the plastic polymer also has various disadvantages, such as the transmission monomer contamination into the material to be packed, and waste is non-biodegradable. Edible film (EF) is an up to date materials, generated after the biodegradable packaging materials. The advantages of the EF materials, is the materials can be eat together with food, and the materials can be applied as a coating materials for a widely kind of foods especially snack foods. The aims of this research are to produce and to analyze the characteristics of smoked EF made from carrageenan, myofibril and collagen of Black Marlin (Makaira indica) industrial waste. Smoked EF made with an addition of 0.8 % smoke liquid. Three biopolymers i.e. carrageenan, myofibril, and collagen were used as treatments, and homogenate for 1 hours at speed of 1500 rpm. The analysis carried out on the pH and physical properties i.e. thickness, solubility, tensile strength, % elongation, and water vapor transmission rate (WVTR), as well as on the sensory characteristics of texture i.e. wateriness, firmness, elasticity, hardness, and juiciness of the coated products. The result shown that the higher the concentration the higher the thickness of EF, where as for myofibril proteins appeared higher than carrageenan and collagen. Both of collagen and myofibril shown that concentration of 6% was most soluble, while for carrageenan were in concentration of 2 to 2.5%. For tensile strength, carrageenan was significantly higher than myofibril and collagen; while for elongation, collagen film more elastic than carragenan and myofibril protein. Water vapor transmission rate, shown that myofibril protein film lower than carrageenan and collagen film. From sensory assessment of texture, carrageenan has a high elasticity and juiciness, while collagen and myofibril have a high in firmness and hardness.Keywords: edible film, collagen, myofibril, carrageenan
Procedia PDF Downloads 4301800 Sulfonic Acid Functionalized Ionic Liquid in Combinatorial Approach: A Recyclable and Water Tolerant-Acidic Catalyst for Friedlander Quinoline Synthesis
Authors: Jafar Akbari
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Quinolines are very important compounds partially because of their pharmacological properties which include wide applications in medicinal chemistry. notable among them are antimalarial drugs, anti-inflammatory agents, antiasthamatic, antibacterial, antihypertensive, and tyrosine kinase inhibiting agents. Despite quinoline usage in pharmaceutical and other industries, comparatively few methods for their preparation have been reported.The Friedlander annulation is one of the simplest and most straightforward methods for the synthesis of poly substituted quinolines. Although, modified methods employing lewis or br¢nsted acids have been reported for the synthesis of quinolines, the development of water stable acidic catalyst for quinoline synthesis is quite desirable. One of the most remarkable features of ionic liquids is that the yields can be optimized by changing the anions or the cations. Recently, sulfonic acid functionalized ionic liquids were used as solvent-catalyst for several organic reactions. We herein report the one pot domino approach for the synthesis of quinoline derivatives in Friedlander manner using TSIL as a catalyst. These ILs are miscible in water, and their homogeneous system is readily separated from the reaction product, combining advantages of both homogeneous and heterogeneous catalysis. In this reaction, the catalyst plays a dual role; it ensures an effective condensation and cyclization of 2-aminoaryl ketone with second carbonyl group and it also promotes the aromatization to the final product. Various types of quinolines from 2-aminoaryl ketones and β-ketoesters/ketones were prepared in 85-98% yields using the catalytic system of SO3-H functionalized ionic liquid/H2O. More importantly, the catalyst could be easily recycled for five times without loss of much activity.Keywords: antimalarial drugs, green chemistry, ionic liquid, quinolines
Procedia PDF Downloads 2101799 Nonparametric Quantile Regression for Multivariate Spatial Data
Authors: S. H. Arnaud Kanga, O. Hili, S. Dabo-Niang
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Spatial prediction is an issue appealing and attracting several fields such as agriculture, environmental sciences, ecology, econometrics, and many others. Although multiple non-parametric prediction methods exist for spatial data, those are based on the conditional expectation. This paper took a different approach by examining a non-parametric spatial predictor of the conditional quantile. The study especially observes the stationary multidimensional spatial process over a rectangular domain. Indeed, the proposed quantile is obtained by inverting the conditional distribution function. Furthermore, the proposed estimator of the conditional distribution function depends on three kernels, where one of them controls the distance between spatial locations, while the other two control the distance between observations. In addition, the almost complete convergence and the convergence in mean order q of the kernel predictor are obtained when the sample considered is alpha-mixing. Such approach of the prediction method gives the advantage of accuracy as it overcomes sensitivity to extreme and outliers values.Keywords: conditional quantile, kernel, nonparametric, stationary
Procedia PDF Downloads 1551798 Community-Based Reference Interval of Selected Clinical Chemistry Parameters Among Apparently Healthy Adolescents in Mekelle City, Tigrai, Northern Ethiopia
Authors: Getachew Belay Kassahun
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Background: Locally established clinical laboratory reference intervals (RIs) are required to interpret laboratory test results for screening, diagnosis, and prognosis. The objective of this study was to establish a reference interval of clinical chemistry parameters among apparently healthy adolescents aged between 12 and 17 years in Mekelle, Tigrai, in the northern part of Ethiopia. Methods: Community-based cross-sectional study was employed from December 2018 to March 2019 in Mekelle City among 172 males and 172 females based on a Multi-stage sampling technique. Blood samples were tested for Fasting blood sugar (FBS), alanine amino transferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), Creatinine, urea, total protein, albumin (ALB), direct and indirect bilirubin (BIL.D and BIL.T) using 25 Bio system clinical chemistry analyzer. Results were analyzed using SPSS version 23 software and based on the Clinical Laboratory Standard Institute (CLSI)/ International Federation of Clinical Chemistry (IFCC) C 28-A3 Guideline which defines the reference interval as the 95% central range of 2.5th and 97.5th percentiles. Mann Whitney U test, descriptive statistics and box and whisker were statistical tools used for analysis. Results: This study observed statistically significant differences between males and females in ALP, ALT, AST, Urea and Creatinine Reference intervals. The established reference intervals for males and females, respectively, were: ALP (U/L) 79.48-492.12 versus 63.56-253.34, ALT (U/L) 4.54-23.69 versus 5.1-20.03, AST 15.7- 39.1 versus 13.3- 28.5, Urea (mg/dL) 9.33-24.99 versus 7.43-23.11, and Creatinine (mg/dL) 0.393-0.957 versus 0.301-0.846. The combined RIs for Total Protein (g/dL) were 6.08-7.85, ALB (g/dL) 4.42-5.46, FBS(mg/dL) 65-110, BIL.D (mg/dL) 0.033-0.532, and BIL.T (mg/dL) 0.106-0.812. Conclusions: The result showed a marked difference between sex and company-derived values for selected clinical chemistry parameters. Thus, the use of age and sex-specific locally established reference intervals for clinical chemistry parameters is recommended.Keywords: reference interval, adolescent, clinical chemistry, Ethiopia
Procedia PDF Downloads 801797 The Examination of Organizational DNA of General Directorate of Youth and Sport Organization of Fars Province Based on Hnald Model
Authors: Mehdi Rastegari Ghiri, Mohammad Reza Baradaran, Zahra Mirsanjari
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The aim of the present study was the investigation of DNA Corporate General Administration of Sports and Youth in Fars province. The descriptive research method is a survey that was conducted by field survey. For data collection, questionnaires were used that designed based on Hnald and Silverman model. In this model the organizational DNA model is stated in four types: objective, individualistic, field-oriented and Spiritual. The reliability of the questionnaire by the researcher obtained by using Cronbach's alpha equal to 89/0 respectively. The statistical population includes all managers and specialists of Fars Province Directorate of Youth and Sport that 48 of them were selected as the samples of the research. The results showed the organizational DNA Directorate General for Youth and Sports Organization of Fars province has a field –oriented and nearly field-oriented DNA.Keywords: organizational, DNA, Hnald, Silverman model
Procedia PDF Downloads 4511796 Ring FingerPortein 2 (RNF2) Targeting by miRNAs in Breast Cancer Cell Lines
Authors: Ceyda Okudu, Secil Eroglu, Khandakar A. S. M. Saadat, Sibel O. Balci
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Ring Finger Protein 2 (RNF2) is a member of polycomb repressive complex 1 (PRC1), which is one of the epigenetic regulators in the genome. When RNF2 combines with other PRC1 members, it mediates the mono-ubiquitination of Histon2A (H2A). In breast cancer, RNF2 is commonly overexpressed, and also it promotes metastasis and invasion in other aggressive tumors like melanoma, prostate, and hepatocarcinoma. The role of RNF2 in the metastasis and invasion of breast cancer has not yet been elucidated. Our aim is to observe the role of RNF2 in metastasis and invasion in this study by miRNA mediated RNF2 gene silencing in breast cancer cell lines. We selected miRNAs, targeting to RNF2 by searching online databases. miR-17-5p, miR20a-5p, and miR-106b-5p were transfected to breast cancer cell lines (MCF-7, MDA-MB-231, SK-BR-3, and ZR-75-1), and also we used normal breast epithelial cell line (hTERT-HME1) to compare RNF2 gene expression level. After 48-72 hours post-transfection, mRNAs were isolated from the cells, and gene expressions were measured by RT-qPCR after from cDNA syntheses. We observed that RNF2 was highly expressed in SK-BR-3 and MDA-MB-231 cell lines opposite to MCF-7 and ZR-75-1 cell lines. RNF2 was downregulated 5, 5 and 7 fold by miR17-5p, miR20a-5p and miR106b-5p respectively in MCF-7. However, in SK-BR-3 and ZR-75-1 cell lines, miRNAs did not affect significantly RNF2 gene expression level. miR20a-5p decreased RNF2 3 fold and miR17-5p and miR106b-5p did not affect MDA-MB-231. After gene expression analysis, we performed metastasis and invasion assay in MCF-7 cells. For metastasis, we used both wound healing assay and Transwell Cell Migration Assay, and we used Transwell Cell Invasion Assay for invasion. The data of this assay showed that miR17-5p and miR20a-5p decreased both invasion and metastasis level, but miR106b-5p has no effect. We would like to conclude that RNF2 can be targeted by miR17-5p, miR20a-5p and miR106b-5p in MCF-7 cells and also RNF2, which is one of the upregulated genes in aggressive tumor, can be decreased by using these miRNAs. In future, we would like to confirm these results at the protein level and also whether these miRNAs are direct target of RNF2 or not.Keywords: breast cancer, epigenetic, microRNAs, RNF2
Procedia PDF Downloads 1801795 Utilization and Characterizations of Olive Oil Industry By-Products
Authors: Sawsan Dacrory, Hussein Abou-Yousef, Samir Kamel, Ragab E. Abou-Zeid, Mohamed S. Abdel-Aziz, Mohamed Elbadry
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A considerable amount of lignocellulosic by-product could be obtained from olive pulp during olive oil extraction industry. The major constituents of the olive pulp are husks and seeds. The separation of each portion of olive pulp (seeds and husks) was carried out by water flotation where seeds were sediment in the bottom. Both seeds and husks were dignified by 15% NaOH followed by complete lignin removal by using sodium chlorite in acidic medium. The isolated holocellulose, α-cellulose, hydrogel and CMC which prepared from cellulose of both seeds and husk fractions were characterized by FTIR and SEM. The present study focused on the investigation of the chemical components of the lignocellulosic fraction of olive pulp. Biofunctionlization of hydrogel was achieved through loading of silver nanoparticles AgNPs in to the prepared hydrogel. The antimicrobial activity of the loaded silver hydrogel against G-ve, and G+ve, and candida was demonstrated.Keywords: cellulose, carboxymethyle cellulose, olive pulp, hydrogel
Procedia PDF Downloads 4751794 Coarse-Graining in Micromagnetic Simulations of Magnetic Hyperthermia
Authors: Razyeh Behbahani, Martin L. Plumer, Ivan Saika-Voivod
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Micromagnetic simulations based on the stochastic Landau-Lifshitz-Gilbert equation are used to calculate dynamic magnetic hysteresis loops relevant to magnetic hyperthermia applications. With the goal to effectively simulate room-temperature loops for large iron-oxide based systems at relatively slow sweep rates on the order of 1 Oe/ns or less, a coarse-graining scheme is proposed and tested. The scheme is derived from a previously developed renormalization-group approach. Loops associated with nanorods, used as building blocks for larger nanoparticles that were employed in preclinical trials (Dennis et al., 2009 Nanotechnology 20 395103), serve as the model test system. The scaling algorithm is shown to produce nearly identical loops over several decades in the model grain sizes. Sweep-rate scaling involving the damping constant alpha is also demonstrated.Keywords: coarse-graining, hyperthermia, hysteresis loops, micromagnetic simulations
Procedia PDF Downloads 1491793 Strengthening Adult Literacy Programs in Order to End Female Genital Mutilation to Achieve Sustainable Development Goals
Authors: Odenigbo Veronica Ngozi, Lorreta Chika Ukwuaba
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This study focuses on how the strengthening adult literacy program can help accelerate transformative strategies to end female genital mutilation (FGM) in Nigeria, specifically in Nsukka Local Government Area. The research delves into the definition of FGM, adult literacy programs, and how to achieve ending FGM to attain Sustainable Development Goals (SDGs) in 2030. It further discusses the practice of FGM in Nigeria and emphasizes the statement of the problem. The main aim of the study is to investigate how strengthening adult literacy programs can help accelerate transformative strategies to end FGM in Nigeria and achieve SDGs in 2030. The researchers utilized a survey research design to conduct the study in Nsukka L.G.A. The population was composed of 26 facilitators and adult learners in five adult learning centers in the area. The entire population was used as a sample, and structured questionnaires were employed to elicit information. The items on the questionnaire were face-validated by three experts, and the reliability of the instrument was verified using Cronbach Alpha Reliability Technique. The research questions were analyzed using means and standard deviation while the hypothesis was tested at 0.05 level of degree of significance using a t-test. The findings show that through adult literacy program acceleration of transformative strategies, the practices of FGM can be ended. Strengthening adult literacy programs is a good channel to end or stop FGM through the knowledge and skill acquired from the learning centers. The theoretical importance of the study lies in the fact that it highlights the role of adult literacy programs in accelerating transformative strategies to combat harmful cultural practices such as FGM. It further supports the importance of education and knowledge in achieving sustainable development goals by 2030. Structured questionnaires were distributed to an entire population of 26 facilitators and adult learners in five adult learning centers in Nsukka L.G.A. The questionnaire items were face–validated by three experts, and the reliability of the instrument was verified using Cronbach Alpha Reliability Technique. The research questions were analyzed using means and standard deviation, while the hypothesis was tested using a t-test at 0.05 level of degree of significance. The study addressed the question of how strengthening adult literacy programs can help accelerate transformative strategies to end FGM in Nigeria and achieve SDGs by 2030. In conclusion, the study found that adult literacy is a good tool to end FGM in Nigeria. The recommendations were that government, non-governmental organizations (NGOs), Community-based organizations (CBOs), and individuals should support the funding and establishment of adult literacy centers in communities so as to reach every illiterate parent or individual and acquire the knowledge and skill needed to understand the negative effect of FGM in the life of a girl child.Keywords: adult literacy, female genital mutilation, learning centers, SDGs, strengthening
Procedia PDF Downloads 691792 LaeA/1-Velvet Interplay in Aspergillus and Trichoderma: Regulation of Secondary Metabolites and Cellulases
Authors: Razieh Karimi Aghcheh, Christian Kubicek, Joseph Strauss, Gerhard Braus
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Filamentous fungi are of considerable economic and social significance for human health, nutrition and in white biotechnology. These organisms are dominant producers of a range of primary metabolites such as citric acid, microbial lipids (biodiesel) and higher unsaturated fatty acids (HUFAs). In particular, they produce also important but structurally complex secondary metabolites with enormous therapeutic applications in pharmaceutical industry, for example: cephalosporin, penicillin, taxol, zeranol and ergot alkaloids. Several fungal secondary metabolites, which are significantly relevant to human health do not only include antibiotics, but also e.g. lovastatin, a well-known antihypercholesterolemic agent produced by Aspergillus. terreus, or aflatoxin, a carcinogen produced by A. flavus. In addition to their roles for human health and agriculture, some fungi are industrially and commercially important: Species of the ascomycete genus Hypocrea spp. (teleomorph of Trichoderma) have been demonstrated as efficient producer of highly active cellulolytic enzymes. This trait makes them effective in disrupting and depolymerization of lignocellulosic materials and thus applicable tools in number of biotechnological areas as diverse as clothes-washing detergent, animal feed, and pulp and fuel productions. Fungal LaeA/LAE1 (Loss of aflR Expression A) homologs their gene products act at the interphase between secondary metabolisms, cellulase production and development. Lack of the corresponding genes results in significant physiological changes including loss of secondary metabolite and lignocellulose degrading enzymes production. At the molecular level, the encoded proteins are presumably methyltransferases or demethylases which act directly or indirectly at heterochromatin and interact with velvet domain proteins. Velvet proteins bind to DNA and affect expression of secondary metabolites (SMs) genes and cellulases. The dynamic interplay between LaeA/LAE1, velvet proteins and additional interaction partners is the key for an understanding of the coordination of metabolic and morphological functions of fungi and is required for a biotechnological control of the formation of desired bioactive products. Aspergilli and Trichoderma represent different biotechnologically significant species with significant differences in the LaeA/LAE1-Velvet protein machinery and their target proteins. We, therefore, performed a comparative study of the interaction partners of this machinery and the dynamics of the various protein-protein interactions using our robust proteomic and mass spectrometry techniques. This enhances our knowledge about the fungal coordination of secondary metabolism, cellulase production and development and thereby will certainly improve recombinant fungal strain construction for the production of industrial secondary metabolite or lignocellulose hydrolytic enzymes.Keywords: cellulases, LaeA/1, proteomics, secondary metabolites
Procedia PDF Downloads 2721791 Collagen Hydrogels Cross-Linked by Squaric Acid
Authors: Joanna Skopinska-Wisniewska, Anna Bajek, Marta Ziegler-Borowska, Alina Sionkowska
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Hydrogels are a class of materials widely used in medicine for many years. Proteins, such as collagen, due to the presence of a large number of functional groups are easily wettable by polar solvents and can create hydrogels. The supramolecular network capable to swelling is created by cross-linking of the biopolymers using various reagents. Many cross-linking agents has been tested for last years, however, researchers still are looking for a new, more secure reactants. Squaric acid, 3,4-dihydroxy 3-cyclobutene 1,2- dione, is a very strong acid, which possess flat and rigid structure. Due to the presence of two carboxyl groups the squaric acid willingly reacts with amino groups of collagen. The main purpose of this study was to investigate the influence of addition of squaric acid on the chemical, physical and biological properties of collagen materials. The collagen type I was extracted from rat tail tendons and 1% solution in 0.1M acetic acid was prepared. The samples were cross-linked by the addition of 5%, 10% and 20% of squaric acid. The mixtures of all reagents were incubated 30 min on magnetic stirrer and then dialyzed against deionized water. The FTIR spectra show that the collagen structure is not changed by cross-linking by squaric acid. Although the mechanical properties of the collagen material deteriorate, the temperature of thermal denaturation of collagen increases after cross-linking, what indicates that the protein network was created. The lyophilized collagen gels exhibit porous structure and the pore size decreases with the higher addition of squaric acid. Also the swelling ability is lower after the cross-linking. The in vitro study demonstrates that the materials are attractive for 3T3 cells. The addition of squaric acid causes formation of cross-ling bonds in the collagen materials and the transparent, stiff hydrogels are obtained. The changes of physicochemical properties of the material are typical for cross-linking process, except mechanical properties – it requires further experiments. However, the results let us to conclude that squaric acid is a suitable cross-linker for protein materials for medicine and tissue engineering.Keywords: collagen, squaric acid, cross-linking, hydrogel
Procedia PDF Downloads 3881790 Gene Expression Signature-Based Chemical Genomic to Identify Potential Therapeutic Compounds for Colorectal Cancer
Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee
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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor
Procedia PDF Downloads 3081789 Mesenchymal Stem Cells on Fibrin Assemblies with Growth Factors
Authors: Elena Filova, Ondrej Kaplan, Marie Markova, Helena Dragounova, Roman Matejka, Eduard Brynda, Lucie Bacakova
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Decellularized vessels have been evaluated as small-diameter vascular prostheses. Reseeding autologous cells onto decellularized tissue prior implantation should prolong prostheses function and make them living tissues. Suitable cell types for reseeding are both endothelial cells and bone marrow-derived stem cells, with a capacity for differentiation into smooth muscle cells upon mechanical loading. Endothelial cells assure antithrombogenicity of the vessels and MSCs produce growth factors and, after their differentiation into smooth muscle cells, they are contractile and produce extracellular matrix proteins as well. Fibrin is a natural scaffold, which allows direct cell adhesion based on integrin receptors. It can be prepared autologous. Fibrin can be modified with bound growth factors, such as basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF). These modifications in turn make the scaffold more attractive for cells ingrowth into the biological scaffold. The aim of the study was to prepare thin surface-attached fibrin assemblies with bound FGF-2 and VEGF, and to evaluate growth and differentiation of bone marrow-derived mesenchymal stem cells on the fibrin (Fb) assemblies. Following thin surface-attached fibrin assemblies were prepared: Fb, Fb+VEGF, Fb+FGF2, Fb+heparin, Fb+heparin+VEGF, Fb+heparin+FGF2, Fb+heparin+FGF2+VEGF. Cell culture poly-styrene and glass coverslips were used as controls. Human MSCs (passage 3) were seeded at the density of 8800 cells/1.5 mL alpha-MEM medium with 2.5% FS and 200 U/mL aprotinin per well of a 24-well cell culture. The cells have been cultured on the samples for 6 days. Cell densities on day 1, 3, and 6 were analyzed after staining with LIVE/DEAD cytotoxicity/viability assay kit. The differentiation of MSCs is being analyzed using qPCR. On day 1, the highest density of MSCs was observed on Fb+VEGF and Fb+FGF2. On days 3 and 6, there were similar densities on all samples. On day 1, cell morphology was polygonal and spread on all sample. On day 3 and 6, MSCs growing on Fb assemblies with FGF2 became apparently elongated. The evaluation of expression of genes for von Willebrand factor and CD31 (endothelial cells), for alpha-actin (smooth muscle cells), and for alkaline phosphatase (osteoblasts) is in progress. We prepared fibrin assemblies with bound VEGF and FGF-2 that supported attachment and growth of mesenchymal stem cells. The layers are promising for improving the ingrowth of MSCs into the biological scaffold. Supported by the Technology Agency of the Czech Republic TA04011345, and Ministry of Health NT11270-4/2010, and BIOCEV – Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University” project (CZ.1.05/1.1.00/02.0109), funded by the European Regional Development Fund for their financial supports.Keywords: fibrin assemblies, FGF-2, mesenchymal stem cells, VEGF
Procedia PDF Downloads 3261788 Swedish–Nigerian Extrusion Research: Channel for Traditional Grain Value Addition
Authors: Kalep Filli, Sophia Wassén, Annika Krona, Mats Stading
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Food security challenge and the growing population in Sub-Saharan Africa centers on its agricultural transformation, where about 70% of its population is directly involved in farming. Research input can create economic opportunities, reduce malnutrition and poverty, and generate faster, fairer growth. Africa is discarding $4 billion worth of grain annually due to pre and post-harvest losses. Grains and tubers play a central role in food supply in the region but their production has generally lagged behind because no robust scientific input to meet up with the challenge. The African grains are still chronically underutilized to the detriment of the well-being of the people of Africa and elsewhere. The major reason for their underutilization is because they are under-researched. Any commitment by scientific community to intervene needs creative solutions focused on innovative approaches that will meet the economic growth. In order to mitigate this hurdle, co-creation activities and initiatives are necessary.An example of such initiatives has been initiated through Modibbo Adama University of Technology Yola, Nigeria and RISE (The Research Institutes of Sweden) Gothenburg, Sweden. Exchange of expertise in research activities as a possibility to create channel for value addition to agricultural commodities in the region under the ´Traditional Grain Network programme´ is in place. Process technologies, such as extrusion offers the possibility of creating products in the food and feed sectors, with better storage stability, added value, lower transportation cost and new markets. The Swedish–Nigerian initiative has focused on the development of high protein pasta. Dry microscopy of pasta sample result shows a continuous structural framework of proteins and starch matrix. The water absorption index (WAI) results showed that water was absorbed steadily and followed the master curve pattern. The WAI values ranged between 250 – 300%. In all aspect, the water absorption history was within a narrow range for all the eight samples. The total cooking time for all the eight samples in our study ranged between 5 – 6 minutes with their respective dry sample diameter ranging between 1.26 – 1.35 mm. The percentage water solubility index (WSI) ranged from 6.03 – 6.50% which was within a narrow range and the cooking loss which is a measure of WSI is considered as one of the main parameters taken into consideration during the assessment of pasta quality. The protein contents of the samples ranged between 17.33 – 18.60 %. The value of the cooked pasta firmness ranged from 0.28 - 0.86 N. The result shows that increase in ratio of cowpea flour and level of pregelatinized cowpea tends to increase the firmness of the pasta. The breaking strength represent index of toughness of the dry pasta ranged and it ranged from 12.9 - 16.5 MPa.Keywords: cowpea, extrusion, gluten free, high protein, pasta, sorghum
Procedia PDF Downloads 1981787 Genetically Modified Organisms
Authors: Mudrika Singhal
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The research paper is basically about how the genetically modified organisms evolved and their significance in today’s world. It also highlights about the various pros and cons of the genetically modified organisms and the progress of India in this field. A genetically modified organism is the one whose genetic material has been altered using genetic engineering techniques. They have a wide range of uses such as transgenic plants, genetically modified mammals such as mouse and also in insects and aquatic life. Their use is rooted back to the time around 12,000 B.C. when humans domesticated plants and animals. At that humans used genetically modified organisms produced by the procedure of selective breeding and not by genetic engineering techniques. Selective breeding is the procedure in which selective traits are bred in plants and animals and then are domesticated. Domestication of wild plants into a suitable cultigen is a well known example of this technique. GMOs have uses in varied fields ranging from biological and medical research, production of pharmaceutical drugs to agricultural fields. The first organisms to be genetically modified were the microbes because of their simpler genetics. At present the genetically modified protein insulin is used to treat diabetes. In the case of plants transgenic plants, genetically modified crops and cisgenic plants are the examples of genetic modification. In the case of mammals, transgenic animals such as mice, rats etc. serve various purposes such as researching human diseases, improvement in animal health etc. Now coming upon the pros and cons related to the genetically modified organisms, pros include crops with higher yield, less growth time and more predictable in comparison to traditional breeding. Cons include that they are dangerous to mammals such as rats, these products contain protein which would trigger allergic reactions. In India presently, group of GMOs include GM microorganisms, transgenic crops and animals. There are varied applications in the field of healthcare and agriculture. In the nutshell, the research paper is about the progress in the field of genetic modification, taking along the effects in today’s world.Keywords: applications, mammals, transgenic, engineering and technology
Procedia PDF Downloads 5981786 The Association of Estrogen Receptor Alpha Xbai Gg Genotype and Severe Preeclampsia
Authors: Saeedeh Salimi, Farzaneh Farajian- Mashhadi, Ehsan Tabatabaei, Mahnaz Shahrakipoor, Minoo Yaghmaei, Mojgan Mokhtari
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Purpose: Estrogen receptor-α (ERα) plays an essential role in the adaptation of increased uterine blood flow during gestation. Therefore ERα gene could be a possible candidate for preeclampsia(PE) susceptibility. In the current study, we aimed to investigate the association of the ERα gene polymorphisms and PE in an Iranian population. Methods: One hundred ninety-two pregnant women with PE and 186 normotensive women were genotyped for ERα gene (PvuII and XbaI) polymorphisms by PCR-RFLP method. Results: The frequency of alleles and genotypes of ERα PvuII and XbaI polymorphisms were not different between PE and normotensive control women. However, higher frequency of GG genotype was observed in women with severe PE compared to mild PE (OR, 1.8 [95% CI, 1.1 to 3]; P = 0.02) and in severe PE compared to normotensive women [OR= 1.8(1.1-3), P=0.02] after adjusting for age, ethnicity and primiparity. Conclusions: The GG genotype of ERα XbaI polymorphism could be a genetic risk factor for PE predisposition.Keywords: estrogen receptor-α, polymorphism, gene, preeclampsia
Procedia PDF Downloads 3091785 Large-Scale Screening for Membrane Protein Interactions Involved in Platelet-Monocyte Interactions
Authors: Yi Sun, George Ed Rainger, Steve P. Watson
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Background: Beyond the classical roles in haemostasis and thrombosis, platelets are important in the initiation and development of various thrombo-inflammatory diseases. In atherosclerosis and deep vein thrombosis, for example, platelets bridge monocytes with endothelium and form heterotypic aggregates with monocytes in the circulation. This can alter monocyte phenotype by inducing their activation, stimulating adhesion and migration. These interactions involve cell surface receptor-ligand pairs on both cells. This list is likely incomplete as new interactions of importance to platelet biology are continuing to be discovered as illustrated by our discovery of PEAR-1 binding to FcεR1α. Results: We have developed a highly sensitive avidity-based assay to identify novel extracellular interactions among 126 recombinantly-expressed platelet cell surface and secreted proteins involved in platelet aggregation. In this study, we will use this method to identify novel platelet-monocyte interactions. We aim to identify ligands for orphan receptors and novel partners of well-known proteins. Identified interactions will be studied in preliminary functional assays to demonstrate relevance to the inflammatory processes supporting atherogenesis. Conclusions: Platelet-monocyte interactions are essential for the development of thromboinflammatory disease. Up until relatively recently, technologies only allow us to limit our studies on each individual protein interaction at a single time. These studies propose for the first time to study the cell surface platelet-monocyte interactions in a systematic large-scale approach using a reliable screening method we have developed. If successful, this will likely to identify previously unknown ligands for important receptors that will be investigated in details and also provide a list of novel interactions for the field. This should stimulate studies on developing alternative therapeutic strategies to treat vascular inflammatory disorders such as atherosclerosis, DVT and sepsis and other clinically important inflammatory conditions.Keywords: membrane proteins, large-scale screening, platelets, recombinant expression
Procedia PDF Downloads 1521784 Regionalization of IDF Curves, by Interpolating Intensity and Adjustment Parameters - Application to Boyacá, Colombia
Authors: Pedro Mauricio Acosta, Carlos Andrés Caro
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This research presents the regionalization of IDF curves for the department of Boyacá, Colombia, which comprises 16 towns, including the provincial capital, Tunja. For regionalization adjustment parameters (U and alpha) of the IDF curves stations referred to in the studied area were used. Similar regionalization is used by the interpolation of intensities. In the case of regionalization by parameters found by the construction of the curves intensity, duration and frequency estimation methods using ordinary moments and maximum likelihood. Regionalization and interpolation of data were performed with the assistance of Arcgis software. Within the development of the project the best choice to provide a level of reliability such as to determine which of the options and ways to regionalize is best sought. The resulting isolines maps were made in the case of regionalization intensities, each map is associated with a different return period and duration in order to build IDF curves in the studied area. In the case of the regionalization maps parameters associated with each parameter were performed last.Keywords: intensity duration, frequency curves, regionalization, hydrology
Procedia PDF Downloads 3281783 Clinical and Analytical Performance of Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase L1 Biomarkers for Traumatic Brain Injury in the Alinity Traumatic Brain Injury Test
Authors: Raj Chandran, Saul Datwyler, Jaime Marino, Daniel West, Karla Grasso, Adam Buss, Hina Syed, Zina Al Sahouri, Jennifer Yen, Krista Caudle, Beth McQuiston
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The Alinity i TBI test is Therapeutic Goods Administration (TGA) registered and is a panel of in vitro diagnostic chemiluminescent microparticle immunoassays for the measurement of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) in plasma and serum. The Alinity i TBI performance was evaluated in a multi-center pivotal study to demonstrate the capability to assist in determining the need for a CT scan of the head in adult subjects (age 18+) presenting with suspected mild TBI (traumatic brain injury) with a Glasgow Coma Scale score of 13 to 15. TBI has been recognized as an important cause of death and disability and is a growing public health problem. An estimated 69 million people globally experience a TBI annually1. Blood-based biomarkers such as glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have shown utility to predict acute traumatic intracranial injury on head CT scans after TBI. A pivotal study using prospectively collected archived (frozen) plasma specimens was conducted to establish the clinical performance of the TBI test on the Alinity i system. The specimens were originally collected in a prospective, multi-center clinical study. Testing of the specimens was performed at three clinical sites in the United States. Performance characteristics such as detection limits, imprecision, linearity, measuring interval, expected values, and interferences were established following Clinical and Laboratory Standards Institute (CLSI) guidance. Of the 1899 mild TBI subjects, 120 had positive head CT scan results; 116 of the 120 specimens had a positive TBI interpretation (Sensitivity 96.7%; 95% CI: 91.7%, 98.7%). Of the 1779 subjects with negative CT scan results, 713 had a negative TBI interpretation (Specificity 40.1%; 95% CI: 37.8, 42.4). The negative predictive value (NPV) of the test was 99.4% (713/717, 95% CI: 98.6%, 99.8%). The analytical measuring interval (AMI) extends from the limit of quantitation (LoQ) to the upper LoQ and is determined by the range that demonstrates acceptable performance for linearity, imprecision, and bias. The AMI is 6.1 to 42,000 pg/mL for GFAP and 26.3 to 25,000 pg/mL for UCH-L1. Overall, within-laboratory imprecision (20 day) ranged from 3.7 to 5.9% CV for GFAP and 3.0 to 6.0% CV for UCH-L1, when including lot and instrument variances. The Alinity i TBI clinical performance results demonstrated high sensitivity and high NPV, supporting the utility to assist in determining the need for a head CT scan in subjects presenting to the emergency department with suspected mild TBI. The GFAP and UCH-L1 assays show robust analytical performance across a broad concentration range of GFAP and UCH-L1 and may serve as a valuable tool to help evaluate TBI patients across the spectrum of mild to severe injury.Keywords: biomarker, diagnostic, neurology, TBI
Procedia PDF Downloads 681782 Wet Processing of Algae for Protein and Carbohydrate Recovery as Co-Product of Algal Oil
Authors: Sahil Kumar, Rajaram Ghadge, Ramesh Bhujade
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Historically, lipid extraction from dried algal biomass remained a focus area of the algal research. It has been realized over the past few years that the lipid-centric approach and conversion technologies that require dry algal biomass have several challenges. Algal culture in cultivation systems contains more than 99% water, with algal concentrations of just a few hundred milligrams per liter ( < 0.05 wt%), which makes harvesting and drying energy intensive. Drying the algal biomass followed by extraction also entails the loss of water and nutrients. In view of these challenges, focus has shifted toward developing processes that will enable oil production from wet algal biomass without drying. Hydrothermal liquefaction (HTL), an emerging technology, is a thermo-chemical conversion process that converts wet biomass to oil and gas using water as a solvent at high temperature and high pressure. HTL processes wet algal slurry containing more than 80% water and significantly reduces the adverse cost impact owing to drying the algal biomass. HTL, being inherently feedstock agnostic, i.e., can convert carbohydrates and proteins also to fuels and recovers water and nutrients. It is most effective with low-lipid (10--30%) algal biomass, and bio-crude yield is two to four times higher than the lipid content in the feedstock. In the early 2010s, research remained focused on increasing the oil yield by optimizing the process conditions of HTL. However, various techno-economic studies showed that simply converting algal biomass to only oil does not make economic sense, particularly in view of low crude oil prices. Making the best use of every component of algae is a key for economic viability of algal to oil process. On investigation of HTL reactions at the molecular level, it has been observed that sequential HTL has the potential to recover value-added products along with biocrude and improve the overall economics of the process. This potential of sequential HTL makes it a most promising technology for converting wet waste to wealth. In this presentation, we will share our experience on the techno-economic and engineering aspects of sequential HTL for conversion of algal biomass to algal bio-oil and co-products.Keywords: algae, biomass, lipid, protein
Procedia PDF Downloads 2161781 Cardiac Hypertrophy in Diabetes; The Role of Factor Forkhead Box Class O-Regulation by O-GlcNAcylation
Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian
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Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin
Procedia PDF Downloads 1081780 Impact of Dietary Rumen Protected Choline on Transition Dairy Cows’ Productive Performance
Authors: Mohamed Ahmed Tony, Fayez Abaza
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The effects of a dietary supplement of rumen-protected choline on feed intake, milk yield, milk composition and some blood metabolites were evaluated in transition dairy cows. Forty multiparous cows were blocked into 20 pairs and then randomly allocated to either one of 2 treatments. The treatments were supplementation either with or without (control) rumen-protected choline. Treatments were applied from 2 weeks before and until 8 weeks after calving. Both groups received the same basal diet as total mixed ration. Additionally, 50 g of a rumen-protected choline supplement (25% rumen protected choline chloride) was added individually in the feed. Individual feed intake, milk yield, and body weight were recorded daily. Milk samples were analyzed weekly for fat, protein, and lactose content. Blood was sampled at week 2 before calving, d 1, d 4, d 7, d 10, week 2, week 3, and week 8 after calving. Glucose, triglycerids, nonesterified fatty acids, and β-hydroxybutyric acid in blood were analysed. The results revealed that choline supplementation increased DM intake from 16.5 to 18.0 kg/d and, hence, net energy intake from 99.2 to 120.5 MJ/d at the intercept of the lactation curve at 1 day in milk. Choline supplementation had no effect on milk yield, milk fat yield, or lactose yield. Milk protein yield was increased from 1.11 to 1.22 kg/d at the intercept of the lactation curve. Choline supplementation was associated with decreased milk fat concentration at the intercept of the lactation curve at 1 day in milking, but the effect of choline on milk fat concentration gradually decreased as lactation progressed. Choline supplementation decreased the concentration of blood triglycerids during the first 4 wk after parturition. Choline supplementation had no effect on energy-corrected milk yield, energy balance, body weight and body condition score. Results from this study suggest that fat metabolism in periparturient dairy cows is improved by choline supplementation during the transition period and this may potentially decrease the risk for metabolic disorders in the periparturient dairy cow.Keywords: choline, dairy cattle, transition cow, triglycerids
Procedia PDF Downloads 5151779 Utilization of Oat in Rabbit Feed for the Development of Healthier Rabbit Meat and Its Impact on Human Blood Lipid Profile
Authors: Muhammad Rizwan Tariq, Muhammad Issa Khan, Zulfiqar Ahmad, Muhammad Adnan Nasir, Muhammad Sameem Javed, Sheraz Ahmed
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Functional foods may be a good tool that can be simply utilized in reducing community health expenses. Regular consumption of rabbit meat can offer patrons with bioactive components because the manipulation in rabbit feed is much successful to raise the levels of conjugated linoleic acid, ecosapentaenoic acid, decosahexaenoic acid, polyunsaturated fatty acids, selenium, tocopherol etc. and to reduce the ω-3/ω-6 ratio which is performing a major role in curing of cardiovascular and several other diseases. In comparison to the meats of other species, rabbit meat has higher amounts of protein with essential amino acids, especially in the muscles and low cholesterol contents that also have elevated digestibility. The present study was carried out to develop the functional rabbit meat by modifying feed ingredient of rabbit diet. Thirty-day old rabbits were fed with feeds containing 2 % and 4 % oat. The feeding trial was carried out for eight weeks. Rabbits were divided into three different groups and reared for the period of two months. T0 rabbits were considered control group while T1 rabbits were reared on 4% oat, and T2 were on 2% oat in the feed. At the end of the 8 weeks, the rabbits were slaughtered. Results presented in this study concluded that 4 % oat seed supplementation enhanced n-3 PUFA in meat. It was observed that oat seed supplementation also reduced fat percentage in the meat. Utilization of oat in the feed of rabbits significantly affected the pH, protein, fat, textural and concentration of polyunsaturated fatty acids. A study trial was conducted in order to examine the impact of functional meat on the blood lipid profile of human subjects. They were given rabbit meat in comparison to the chicken meat for the period of one month. The cholesterol, triglycerides and low density lipoprotein were found to be lower in blood serum of human subject group treated with 4 % oat meat.Keywords: functional food, functional rabbit meat, meat quality, rabbit
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