Search results for: genetic expression programming
3898 The Effect of Resistance and Progressive Training on Hsp 70 and Glucose
Authors: F. Nameni, H. Poursadra
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The present study investigated resistance and progressive training alters the expression of chaperone proteins. These proteins function to maintain homeostasis, facilitate repair from injury, and provide protection. Nineteen training female in 2 groups taking part in the intervention volunteered to give blood samples. Levels of chaperone proteins were measured in response to resistance and progressive training. Hsp 70 levels were increased immediately after 2 h progressive training but decreased after resistance training. The data showed that human skeletal muscle responds to the stress of a single period of progressive training by up-regulating and resistance training by down-regulating expression of HSP70. Physical exercise can elevate core temperature and muscle temperatures and the expression pattern of HSP70 due to training status may be attributed to adaptive mechanisms.Keywords: resistance training, heat shock proteins, leukocytes, Hsp 70
Procedia PDF Downloads 4553897 Interval Bilevel Linear Fractional Programming
Authors: F. Hamidi, N. Amiri, H. Mishmast Nehi
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The Bilevel Programming (BP) model has been presented for a decision making process that consists of two decision makers in a hierarchical structure. In fact, BP is a model for a static two person game (the leader player in the upper level and the follower player in the lower level) wherein each player tries to optimize his/her personal objective function under dependent constraints; this game is sequential and non-cooperative. The decision making variables are divided between the two players and one’s choice affects the other’s benefit and choices. In other words, BP consists of two nested optimization problems with two objective functions (upper and lower) where the constraint region of the upper level problem is implicitly determined by the lower level problem. In real cases, the coefficients of an optimization problem may not be precise, i.e. they may be interval. In this paper we develop an algorithm for solving interval bilevel linear fractional programming problems. That is to say, bilevel problems in which both objective functions are linear fractional, the coefficients are interval and the common constraint region is a polyhedron. From the original problem, the best and the worst bilevel linear fractional problems have been derived and then, using the extended Charnes and Cooper transformation, each fractional problem can be reduced to a linear problem. Then we can find the best and the worst optimal values of the leader objective function by two algorithms.Keywords: best and worst optimal solutions, bilevel programming, fractional, interval coefficients
Procedia PDF Downloads 4443896 Identification of the Expression of Top Deregulated MiRNAs in Rheumatoid Arthritis and Osteoarthritis
Authors: Hala Raslan, Noha Eltaweel, Hanaa Rasmi, Solaf Kamel, May Magdy, Sherif Ismail, Khalda Amr
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Introduction: Rheumatoid arthritis (RA) is an inflammatory, autoimmune disorder with progressive joint damage. Osteoarthritis (OA) is a degenerative disease of the articular cartilage that shows multiple clinical manifestations or symptoms resembling those of RA. Genetic predisposition is believed to be a principal etiological factor for RA and OA. In this study, we aimed to measure the expression of the top deregulated miRNAs that might be the cause of pathogenesis in both diseases, according to our latest NGS analysis. Six of the deregulated miRNAs were selected as they had multiple target genes in the RA pathway, so they are more likely to affect the RA pathogenesis.Methods: Eighty cases were recruited in this study; 45 rheumatoid arthiritis (RA), 30 osteoarthiritis (OA) patients, as well as 20 healthy controls. The selection of the miRNAs from our latest NGS study was done using miRwalk according to the number of their target genes that are members in the KEGG RA pathway. Total RNA was isolated from plasma of all recruited cases. The cDNA was generated by the miRcury RT Kit then used as a template for real-time PCR with miRcury Primer Assays and the miRcury SYBR Green PCR Kit. Fold changes were calculated from CT values using the ΔΔCT method of relative quantification. Results were compared RA vs Controls and OA vs Controls. Target gene prediction and functional annotation of the deregulated miRNAs was done using Mienturnet. Results: Six miRNAs were selected. They were miR-15b-3p, -128-3p, -194-3p, -328-3p, -542-3p and -3180-5p. In RA samples, three of the measured miRNAs were upregulated (miR-194, -542, and -3180; mean Rq= 2.6, 3.8 and 8.05; P-value= 0.07, 0.05 and 0.01; respectively) while the remaining 3 were downregulated (miR-15b, -128 and -328; mean Rq= 0.21, 0.39 and 0.6; P-value= <0.0001, <0.0001 and 0.02; respectively) all with high statistical significance except miR-194. While in OA samples, two of the measured miRNAs were upregulated (miR-194 and -3180; mean Rq= 2.6 and 7.7; P-value= 0.1 and 0.03; respectively) while the remaining 4 were downregulated (miR-15b, -128, -328 and -542; mean Rq= 0.5, 0.03, 0.08 and 0.5; P-value= 0.0008, 0.003, 0.006 and 0.4; respectively) with statistical significance compared to controls except miR-194 and miR-542. The functional enrichment of the selected top deregulated miRNAs revealed the highly enriched KEGG pathways and GO terms. Conclusion: Five of the studied miRNAs were greatly deregulated in RA and OA, they might be highly involved in the disease pathogenesis and so might be future therapeutic targets. Further functional studies are crucial to assess their roles and actual target genes.Keywords: MiRNAs, expression, rheumatoid arthritis, osteoarthritis
Procedia PDF Downloads 773895 Expression of ULK-1 mRNA in Human Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease
Authors: Ali Bayram, Remzi Yiğiter
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Objective: Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. At present, diagnosis of AD is rather late in the disease. Therefore, we attempted to find peripheral biomarkers for the early diagnosis of AD. Herein, we conducted a study to investigate the unc-51 like autophagy activating kinase-1 (ULK1) mRNA expression levels in human peripheral blood mononuclear cells from patients with Alzheimer's disease. Method: To determine whether ULK1 gene expression are altered in AD patients, we measured their gene expression in human peripheral blood cell in 50 patients with AD and 50 age and gender matched healthy controls by quantitative real-time PCR technique. Results: We found that both ULK1 gene expression in peripheral blood cell were significantly decreased in patients with AD as compared with controls (p <0.05). Lower levels of ULK1 gene expression were significantly associated with the increased risk for AD. Conclusions: Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2, and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. Alzheimer is the most common neurodegenerative disease. Our results provide useful information that the ULK1 gene expression is decreased in the neurodegeneration and AD patients with, indicating their possible systemic involvement in AD.Keywords: Alzheimer’s sisease, ULK1, mRNA expression, RT-PCR
Procedia PDF Downloads 3963894 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
Procedia PDF Downloads 703893 In Vitro Propagation of Aloe vera and Aloe littoralis Plants: Gamma Radiation, Biochemical and Genetic Changes
Authors: Z. Nourmohammadi, F. Farahani, M. Shaker
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Aloe is an important commercial crop available in a wide range of species and varieties in international markets. The applications of this plant have been recorded in the ancient cultures of India, Egypt, Greece, Rome and China. Aloe has been used for centuries and is currently being actively studied for medicinal purposes. Aloe is propagated through lateral buds, which is slow, very expensive and low income practice. Nowadays, it has been cultured by in vitro propagation for rapid multiplication of plants, genetic improvement of crops, obtaining disease-free clones and for progressive valuable germplasm. The present study focused on the influence of different phytohormones on rapid in vitro propagation of Aloe plants. We also investigated the effect of gamma radiation on biochemical characters as well as genetic changes. Shoot tip of 2-3 cm were collected from offshoot of Aloe barbadensis and Aloe littoralis, and were inoculated with MS medium containing various concentrations of BA (0.5, 1, 2 mg/l), IAA (0.5, 1 mg/l). The best treatment for a highest shoot number and bud proliferation was MS medium containing 2 mg/l BAP and 0.5 mg/l IAA in A. barbadensis and A. littoralis. Maximum percentage of proliferated shoot buds (90% and 95%) from a single explant were obtained in MS medium after 4-5 weeks of the second and the first subcultures, respectively. Different genome sizes were also indicated among treatments and subcultures. The mixoploids identified in flow cytometery histograms in different treatments. The effect of gamma radiation on A. littoralis showed that by increasing the dose of gamma radiation, amounts of chlorophyll A, B, carotenoids, total protein content and superoxide dismutase were significantly increased compared to control plants. Genetic variation analysis also revealed significant genetic differences between control and gamma radiation treated regenerated plants by AMOVA test. Higher genetic heterozygocity was observed in radiation treated plants. Our findings may provide useful method for improving of Aloe plant proliferation with increasing of useful material such as antioxidant enzymes.Keywords: aloe, antioxidant enzyme, micropropagation, gamma radiation, genetic variation
Procedia PDF Downloads 4253892 Variability Parameters for Growth and Yield Characters in Fenugreek, Trigonella spp. Genotypes
Authors: Anita Singh, Richa Naula, Manoj Raghav
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India is a leading producer and consumer of fenugreek for its culinary uses and medicinal application. In India, most of the people are of vegetarian class. In such a situation, a leafy vegetable, such as fenugreek is of chief concern due to its high nutritional property, medicinal values and industrial uses. One of the most important factors restricting their large scale production and development of superior varieties is that very scanty knowledge about their genetic diversity, inter and intraspecific variability and genetic relationship among the species. Improvement of the crop depends upon the magnitude of genetic variability for economic characters. Therefore, the present research work was carried out to analyse the variability parameters for growth and yield character in twenty-eight fenugreek genotypes along with two standard checks Pant Ragini and Pusa Early Bunching. The experiment was laid out in Randomized Block Design with three replication during rabi season 2015-2016 at Pantnagar Centre for Plant Genetic Resources, G.B. Pant University of Agriculture and Technology, Pantnagar, Uttarakhand. The analysis of variance revealed highly significant differences among all the genotypes for all traits. High genotypic and phenotypic coefficient variation were observed for characters, namely the number of primary branches per plant, number of leaves at 30, 45 and 60 DAS, green leaf yield per plant, green leaf yield q/ha . The genetic advance recorded highest in green leaf yield q/ha (33.93) followed by green leaf yield per plant (21.20g). Highest percent of heritability were shown by 1000 seed weight (99.12%) followed by the number of primary branches per plant (97.18%). Green leaf yield q/ha showed high heritability and high genetic advance. These superior genotypes can be further used in crop improvement programs of fenugreek.Keywords: genetic advance, genotypic coefficient variation, heritability, phenotypic coefficient variation
Procedia PDF Downloads 3203891 Role of Long Noncoding RNA HULC on Colorectal Carcinoma Progression through Epigenetically Repressing NKD2 Expression
Authors: Shu-Jun Li, Cheng-Cao Sun, De-Jia Li
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Recently, long noncoding RNAs (lncRNAs) have been emerged as crucial regulators of human diseases and prognostic markers in numerous of cancers, including colorectal carcinoma (CRC). Here, we identified an oncogenetic lncRNA HULC, which may promote colorectal tumorigenesis. HULC has been found to be up-regulated and acts as oncogene in gastric cancer and hepatocellular carcinoma, but its expression pattern, biological function and underlying mechanism in CRC is still undetermined. Here, we reported that HULC expression is also over-expressed in CRC, and its increased level is associated with poor prognosis and shorter survival. Knockdown of HULC impaired CRC cells proliferation, migration and invasion, facilitated cell apoptosis in vitro, and inhibited tumorigenicity of CRC cells in vivo. Mechanistically, RNA immunoprecipitation (RIP) and RNA pull-down experiment demonstrated that HULC could simultaneously interact with EZH2 to repress underlying targets NKD2 transcription. In addition, rescue experiments determined that HULC oncogenic function is partly dependent on repressing NKD2. Taken together, our findings expound how HULC over-expression endows an oncogenic function in CRC.Keywords: long noncoding RNA, HULC, NKD2, colorectal carcinoma, proliferation, apoptosis
Procedia PDF Downloads 2243890 Anti-Inflammatory Studies on Chungpye-Tang in Asthmatic Human Lung Tissue
Authors: J. H. Bang, H. J. Baek, K. I. Kim, B. J. Lee, H. J. Jung, H. J. Jang, S. K. Jung
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Asthma is a chronic inflammatory lung disease characterized by airway hyper responsiveness (AHR), airway obstruction and airway wall remodeling responsible for significant morbidity and mortality worldwide. Genetic and environment factors may result in asthma, but there are no the exact causes of asthma. Chungpye-tang (CPT) has been prescribed as a representative aerosol agent for patients with dyspnea, cough and phlegm in the respiratory clinic at Kyung Hee Korean Medicine Hospital. This Korean herbal medicines have the effect of dispelling external pathogen and dampness pattern. CPT is composed of 4 species of herbal medicines. The 4 species of herbal medicines are Ephedrae herba, Pogostemonis(Agatachis) herba, Caryophylli flos and Zingiberis rhizoma crudus. CPT suppresses neutrophil infiltration and the production of pro-inflammatory cytokines in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Moreover, the anti-inflammatory effects of CPT on a mouse model of Chronic Obstructive Pulmonary Disease (COPD) was proved. Activation of the NF-κB has been proven that it plays an important role in inflammation via inducing transcription of pro-inflammatory genes. Over-expression of NF-κB has been believed be related to many inflammatory diseases such as arthritis, gastritis, asthma and COPD. So we firstly hypothesize whether CPT has an anti-inflammatory effect on asthmatic human airway epithelial tissue via inhibiting NF-κB pathway. In this study, CPT was extracted with distilled water for 3 hours at 100°C. After process of filtration and evaporation, it was freeze dried. And asthmatic human lung tissues were provided by MatTek Corp. We investigated the precise mechanism of the anti-inflammatory effect of CPT by western blotting analysis. We observed whether the decoction extracts could reduce NF-κB activation, COX-2 protein expression and NF-κB-mediated pro-inflammatory cytokines such as TNF-α, eotaxin, IL-4, IL-9 and IL-13 in asthmatic human lung tissue. As results of this study, there was a trend toward decreased NF-κB expression in asthmatic human airway epithelial tissue. We found that the inhibition effects of CPT on COX-2 expression was not determined. IL-9 and IL-13 secretion was significantly reduced in the asthmatic human lung tissue treated with CPT. Overall, our results indicate that CPT has an anti-inflammatory effect through blocking the signaling pathway of NF-κB, thereby CPT may be a potential remedial agent for allergic asthma.Keywords: Chungpye-tang, allergic asthma, asthmatic human airway epithelial tissue, nuclear factor kappa B (NF-κB) pathway, COX-2
Procedia PDF Downloads 3343889 Transcriptome Analysis of Protestia brevitarsis seulensis with Focus On Wing Development and Metamorphosis in Developmental Stages
Authors: Jihye Hwang, Eun Hwa Choi, Su Youn Baek, Bia Park, Gyeongmin Kim, Chorong Shin, Joon Ha Lee, Jae-Sam Hwang, Ui Wook Hwang
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White-spotted flower chafers are widely distributed in Asian countries and traditionally used for the treatment of chronic fatigue, blood circulation, and paralysis in the oriental medicine field. The evolution and development of insect wings and metamorphosis remain under-discovered subjects in arthropod evolutionary researches. Gene expression abundance analyses along with developmental stages based on the large-scale RNA-seq data are also still rarely done. Here we report the de novo assembly of a Protestia brevitarsis seulensis transcriptome along four different developmental stages (egg, larva, pupa, and adult) to explore its development and evolution of wings and metamorphosis. The de novo transcriptome assembly consists of 23,551 high-quality transcripts and is approximately 96.7% complete. Out of 8,545 transcripts, 5,183 correspond to the possible orthologs with Drosophila melanogaster. As a result, we could found 265 genes related to wing development and 19 genes related to metamorphosis. The comparison of transcript expression abundance with different developmental stages revealed developmental stage-specific transcripts especially working at the stage of wing development and metamorphosis of P. b. seulensis. This transcriptome quantification along the developmental stages may provide some meaningful clues to elucidate the genetic modulation mechanism of wing development and metamorphosis obtained during the insect evolution.Keywords: white-spotted flower chafers, transcriptomics, RNA-seq, network biology, wing development, metamorphosis
Procedia PDF Downloads 2273888 MicroRNA Differential Profiling in Hepatitis C Patients Undergoing Major Surgeries: Propofol versus Sevoflurane Anesthesia
Authors: Hala Demerdash, Ola M. Zanaty, Emad Eldin Arida
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Background: This study investigated the micoRNA expression changes induced by Sevoflurane and Propofol and their effects on liver functions. Patients and methods: The study was designed as randomized controlled study, carried out on 200 adult patients, scheduled for major surgeries under general anesthesia (GA). Patients were randomly divided into four groups; groups SC and PC included chronic hepatitis C (CHC) patients where SC group are patients receiving Sevoflurane, and PC group are patients receiving Propofol anesthesia. While S and P groups included non- hepatitis patients; S group are patients receiving Sevoflurane and P group are patients receiving Propofol. Anesthesia in Group S and SC patients was maintained by sevoflurane, while anesthesia in Group P and PC patients was maintained by propofol infusion. Blood samples were analyzed for PT, PTT and liver enzymes. Serum samples were analyzed for microRNA before and after surgery. Results: Results show miRNA-122 and miRNA-21 were absent in serum of S and P groups in pre-operative samples. However, they were expressed in SC and PC groups. In post-operative samples; miRNA-122 revealed an increased expression in all groups; with more exaggerated response in SC group. On the other hand miRNA-21 revealed increased expression in both SC and PC groups; a slight expression in S group with absent expression in P group. There was a post-operative negative correlation between miR-122 and ALT (r=-0.46) in SC group and (r=-0.411) in PC group and positive correlation between ALT and miR-21 (r=0.335) in SC group and (r=0.379) in PC group. The amount of blood loss was positively correlated with miR-122 (r=0.366) in SC group and (r=0.384) in PC group. Conclusion: Propofol anesthesia is safer than Sevoflurane anesthesia in patients with CHC. Sevoflurane and Propofol anesthesia affect miRNA expression in both CHC and non-hepatitis patients.Keywords: anesthesia, chronic hepatitis C, micoRNA, propofol, sevoflurane
Procedia PDF Downloads 3403887 The Molecular Characteristic of Heliotropium digynum in Saudi Arabia by Inter-Simple Sequence Repeat (ISSR) Analysis
Authors: Mona Alwhibi, Najat Bukhary
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Heliotropium digynum, a member of Boraginaceae family, the growth of the plant, as well as its size, length of inflorescence, and speed of development depends on the amount of rain in its habitat. In this study, we studied the applicability of inter-simple sequence repeat (ISSR) polymorphism in Heliotropium digynum in a different region of Saudi Arabia. We found that. ISSR analysis using 15 primers were used for ISSR-PCR optimization trials, five primers (UBC810, UBC811, UBC818, UBC834, and UBC849) which gave the best amplification results produced a total of 43 polymorphic bands. The number of polymorphic loci was 20 and the percentage of polymorphism was 90.47%. The similarity result indicates the presence of a high-level genetic diversity between populations and a dendrogram constructed by UPGMA method.Keywords: genetic differentiation, genetic diversity, Heliotropium digynum, ISSR
Procedia PDF Downloads 4793886 A Novel Algorithm for Production Scheduling
Authors: Ali Mohammadi Bolban Abad, Fariborz Ahmadi
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Optimization in manufacture is a method to use limited resources to obtain the best performance and reduce waste. In this paper a new algorithm based on eurygaster life is introduced to obtain a plane in which task order and completion time of resources are defined. Evaluation results show our approach has less make span when the resources are allocated with some products in comparison to genetic algorithm.Keywords: evolutionary computation, genetic algorithm, particle swarm optimization, NP-Hard problems, production scheduling
Procedia PDF Downloads 3763885 Immunolabeling of TGF-β during Muscle Regeneration
Authors: K. Nikovics, D. Riccobono, M. Oger, H. Morin, L. Barbier, T. Poyot, X. Holy, A. Bendahmane, M. Drouet, A. L. Favier
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Muscle regeneration after injury (as irradiation) is of great importance. However, the molecular and cellular mechanisms are still unclear. Cytokines are believed to play fundamental role in the different stages of muscle regeneration. They are secreted by many cell populations, but the predominant producers are macrophages and helper T cells. On the other hand, it has been shown that adipose tissue derived stromal/stem cell (ASC) injection could improve muscle regeneration. Stem cells probably induce the coordinated modulations of gene expression in different macrophage cells. Therefore, we investigated the patterns and timing of changes in gene expression of different cytokines occurring upon stem cells loading. Muscle regeneration was studied in an irradiated muscle of minipig animal model in presence or absence of ASC treatment (irradiated and treated with ASCs, IRR+ASC; irradiated not-treated with ASCs, IRR; and non-irradiated no-IRR). We characterized macrophage populations by immunolabeling in the different conditions. In our study, we found mostly M2 and a few M1 macrophages in the IRR+ASC samples. However, only few M2b macrophages were noticed in the IRR muscles. In addition, we found intensive fibrosis in the IRR samples. With in situ hybridization and immunolabeling, we analyzed the cytokine expression of the different macrophages and we showed that M2d macrophage are the most abundant in the IRR+ASC samples. By in situ hybridization, strong expression of the transforming growth factor β (TGF-β) was observed in the IRR+ASC but very week in the IRR samples. But when we analyzed TGF-β level with immunolabeling the expression was very different: many M2 macrophages showed week expression in IRR+ASC and few cells expressing stronger level in IRR muscles. Therefore, we investigated the MMP expressions in the different muscles. Our data showed that the M2 macrophages of the IRR+ASC muscle expressed MMP2 proteins. Our working hypothesis is that MMP2 expression of the M2 macrophages can decrease fibrosis in the IRR+ASC muscle by capturing TGF-β.Keywords: adipose tissue derived stromal/stem cell, cytokine, macrophage, muscle regeneration
Procedia PDF Downloads 2303884 The Effects of Highly Active Antiretroviral Therapy (HAART) on the Expression of Muc1 and P65 in a Cervical Cancer Cell Line, HCS-2
Authors: K. R. Thabethe, G. A. Adefolaju, M. J. Hosie
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Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24 hour treatment of a cervical cancer cell line, HCS-2, with drugs which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one way ANOVA followed by a Tukey Kramer Post Hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death, therefore the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.Keywords: cervical cancer, haart, MUC1, P65
Procedia PDF Downloads 3313883 lncRNA Gene Expression Profiling Analysis by TCGA RNA-Seq Data of Breast Cancer
Authors: Xiaoping Su, Gabriel G. Malouf
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Introduction: Breast cancer is a heterogeneous disease that can be classified in 4 subgroups using transcriptional profiling. The role of lncRNA expression in human breast cancer biology, prognosis, and molecular classification remains unknown. Methods and results: Using an integrative comprehensive analysis of lncRNA, mRNA and DNA methylation in 900 breast cancer patients from The Cancer Genome Atlas (TCGA) project, we unraveled the molecular portraits of 1,700 expressed lncRNA. Some of those lncRNAs (i.e, HOTAIR) are previously reported and others are novel (i.e, HOTAIRM1, MAPT-AS1). The lncRNA classification correlated well with the PAM50 classification for basal-like, Her-2 enriched and luminal B subgroups, in contrast to the luminal A subgroup which behaved differently. Importantly, estrogen receptor (ESR1) expression was associated with distinct lncRNA networks in lncRNA clusters III and IV. Gene set enrichment analysis for cis- and trans-acting lncRNA showed enrichment for breast cancer signatures driven by breast cancer master regulators. Almost two third of those lncRNA were marked by enhancer chromatin modifications (i.e., H3K27ac), suggesting that lncRNA expression may result in increased activity of neighboring genes. Differential analysis of gene expression profiling data showed that lncRNA HOTAIRM1 was significantly down-regulated in basal-like subtype, and DNA methylation profiling data showed that lncRNA HOTAIRM1 was highly methylated in basal-like subtype. Thus, our integrative analysis of gene expression and DNA methylation strongly suggested that lncRNA HOTAIRM1 should be a tumor suppressor in basal-like subtype. Conclusion and significance: Our study depicts the first lncRNA molecular portrait of breast cancer and shows that lncRNA HOTAIRM1 might be a novel tumor suppressor.Keywords: lncRNA profiling, breast cancer, HOTAIRM1, tumor suppressor
Procedia PDF Downloads 1043882 Genetic Evaluation of Locally Flock Sheep in Gabaraka Village
Authors: Salim Omar Raoof
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This study was conducted in a private local sheep herd at Gabaraka village-Kirkuk-Iraq. Analysis of 77 ewes recorded and 7 Rams of local sheep presented in Gabaraka village farm plain, the age of ewes ranged between (2-4) years. The aim of this study is to investigate the genetic and non-genetic factors (type of birth, sex, and age of dam) affecting daily milk yield (DMY), birth weight (BW), weaning weight (WW) and Gain characteristics of local sheep raised under Iraq conditions, and it also aims at estimating heritability’s, BLUP. The overall mean of daily milk yield, (BW), (WW), and gain. Was 444.15gm,4.92kg,43.08kg, and 38.16kg, respectively. The results showed there was a significant effect of the type of birth and sex on (BW) and (WW). Also, the age of the dam had a significant effect on daily milk yield (BW), (WW), and gain. Generally, the estimate of heritability of DMP, BWT, WWT, and Gain tend to be 0.22, 0.17, 0.27, and 0.22, respectively. The breeding value (BLUP) for rams ranged between (-0.1684 to 0.188), (-0.205 to 0.310), and ( -0.0171 to 0.029) according to growth traits of Lambs BW, WW, and Gain, respectively. It concluded that the selection of ewes and rams at the population level in planned selection schemes is based on BLUP value and heritability.Keywords: locally sheep, milk yield, Genetic parameters, BLUP value
Procedia PDF Downloads 743881 A User-Directed Approach to Optimization via Metaprogramming
Authors: Eashan Hatti
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In software development, programmers often must make a choice between high-level programming and high-performance programs. High-level programming encourages the use of complex, pervasive abstractions. However, the use of these abstractions degrades performance-high performance demands that programs be low-level. In a compiler, the optimizer attempts to let the user have both. The optimizer takes high-level, abstract code as an input and produces low-level, performant code as an output. However, there is a problem with having the optimizer be a built-in part of the compiler. Domain-specific abstractions implemented as libraries are common in high-level languages. As a language’s library ecosystem grows, so does the number of abstractions that programmers will use. If these abstractions are to be performant, the optimizer must be extended with new optimizations to target them, or these abstractions must rely on existing general-purpose optimizations. The latter is often not as effective as needed. The former presents too significant of an effort for the compiler developers, as they are the only ones who can extend the language with new optimizations. Thus, the language becomes more high-level, yet the optimizer – and, in turn, program performance – falls behind. Programmers are again confronted with a choice between high-level programming and high-performance programs. To investigate a potential solution to this problem, we developed Peridot, a prototype programming language. Peridot’s main contribution is that it enables library developers to easily extend the language with new optimizations themselves. This allows the optimization workload to be taken off the compiler developers’ hands and given to a much larger set of people who can specialize in each problem domain. Because of this, optimizations can be much more effective while also being much more numerous. To enable this, Peridot supports metaprogramming designed for implementing program transformations. The language is split into two fragments or “levels”, one for metaprogramming, the other for high-level general-purpose programming. The metaprogramming level supports logic programming. Peridot’s key idea is that optimizations are simply implemented as metaprograms. The meta level supports several specific features which make it particularly suited to implementing optimizers. For instance, metaprograms can automatically deduce equalities between the programs they are optimizing via unification, deal with variable binding declaratively via higher-order abstract syntax, and avoid the phase-ordering problem via non-determinism. We have found that this design centered around logic programming makes optimizers concise and easy to write compared to their equivalents in functional or imperative languages. Overall, implementing Peridot has shown that its design is a viable solution to the problem of writing code which is both high-level and performant.Keywords: optimization, metaprogramming, logic programming, abstraction
Procedia PDF Downloads 853880 Genetic Diversity Analysis in Ecological Populations of Persian Walnut
Authors: Masoud Sheidai, Fahimeh Koohdar, Hashem Sharifi
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Juglans regia (L.) commonly known as Persian walnut of the genus Juglans L. (Juglandaceae) is one of the most important cultivated plant species due to its high-quality wood and edible nuts. The genetic diversity analysis is essential for conservation and management of tree species. Persian walnut is native from South-Eastern Europe to North-Western China through Tibet, Nepal, Northern India, Pakistan, and Iran. The species like Persian walnut, which has a wide range of geographical distribution, should harbor extensive genetic variability to adapt to environmental fluctuations they face. We aimed to study the population genetic structure of seven Persian walnut populations including three wild and four cultivated populations by using ISSR (Inter simple sequence repeats) and SRAP (Sequence related amplified polymorphism) molecular markers. We also aimed to compare the genetic variability revealed by ISSR neutral multilocus marker and rDNA ITS sequences. The studied populations differed in morphological features as the samples in each population were clustered together and were separate from the other populations. Three wild populations studied were placed close to each other. The mantel test after 5000 times permutation performed between geographical distance and morphological distance in Persian walnut populations produced significant correlation (r = 0.48, P = 0.002). Therefore, as the populations become farther apart, they become more divergent in morphological features. ISSR analysis produced 47 bands/ loci, while we obtained 15 SRAP bands. Gst and other differentiation statistics determined for these loci revealed that most of the ISSR and SRAP loci have very good discrimination power and can differentiate the studied populations. AMOVA performed for these loci produced a significant difference (< 0.05) supporting the above-said result. AMOVA produced significant genetic difference based on ISSR data among the studied populations (PhiPT = 0.52, P = 0.001). AMOVA revealed that 53% of the total variability is due to among population genetic difference, while 47% is due to within population genetic variability. The results showed that both multilocus molecular markers and ITS sequences can differentiate Persian walnut populations. The studied populations differed genetically and showed isolation by distance (IBD). ITS sequence based MP and Bayesian phylogenetic trees revealed that Iranian walnut cultivars form a distinct clade separated from the cultivars studied from elsewhere. Almost all clades obtained have high bootstrap value. The results indicated that a combination of multilpcus and sequencing molecular markers can be used in genetic differentiation of Persian walnut.Keywords: genetic diversity, population, molecular markers, genetic difference
Procedia PDF Downloads 1613879 Network Analysis of Genes Involved in the Biosynthesis of Medicinally Important Naphthodianthrone Derivatives of Hypericum perforatum
Authors: Nafiseh Noormohammadi, Ahmad Sobhani Najafabadi
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Hypericins (hypericin and pseudohypericin) are natural napthodianthrone derivatives produced by Hypericum perforatum (St. John’s Wort), which have many medicinal properties such as antitumor, antineoplastic, antiviral, and antidepressant activities. Production and accumulation of hypericin in the plant are influenced by both genetic and environmental conditions. Despite the existence of different high-throughput data on the plant, genetic dimensions of hypericin biosynthesis have not yet been completely understood. In this research, 21 high-quality RNA-seq data on different parts of the plant were integrated into metabolic data to reconstruct a coexpression network. Results showed that a cluster of 30 transcripts was correlated with total hypericin. The identified transcripts were divided into three main groups based on their functions, including hypericin biosynthesis genes, transporters, detoxification genes, and transcription factors (TFs). In the biosynthetic group, different isoforms of polyketide synthase (PKSs) and phenolic oxidative coupling proteins (POCPs) were identified. Phylogenetic analysis of protein sequences integrated into gene expression analysis showed that some of the POCPs seem to be very important in the biosynthetic pathway of hypericin. In the TFs group, six TFs were correlated with total hypericin. qPCR analysis of these six TFs confirmed that three of them were highly correlated. The identified genes in this research are a rich resource for further studies on the molecular breeding of H. perforatum in order to obtain varieties with high hypericin production.Keywords: hypericin, St. John’s Wort, data mining, transcription factors, secondary metabolites
Procedia PDF Downloads 893878 A Robust Optimization Model for the Single-Depot Capacitated Location-Routing Problem
Authors: Abdolsalam Ghaderi
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In this paper, the single-depot capacitated location-routing problem under uncertainty is presented. The problem aims to find the optimal location of a single depot and the routing of vehicles to serve the customers when the parameters may change under different circumstances. This problem has many applications, especially in the area of supply chain management and distribution systems. To get closer to real-world situations, travel time of vehicles, the fixed cost of vehicles usage and customers’ demand are considered as a source of uncertainty. A combined approach including robust optimization and stochastic programming was presented to deal with the uncertainty in the problem at hand. For this purpose, a mixed integer programming model is developed and a heuristic algorithm based on Variable Neighborhood Search(VNS) is presented to solve the model. Finally, the computational results are presented and future research directions are discussed.Keywords: location-routing problem, robust optimization, stochastic programming, variable neighborhood search
Procedia PDF Downloads 2653877 Evaluation of Yield and Yield Components of Malaysian Palm Oil Board-Senegal Oil Palm Germplasm Using Multivariate Tools
Authors: Khin Aye Myint, Mohd Rafii Yusop, Mohd Yusoff Abd Samad, Shairul Izan Ramlee, Mohd Din Amiruddin, Zulkifli Yaakub
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The narrow base of genetic is the main obstacle of breeding and genetic improvement in oil palm industry. In order to broaden the genetic bases, the Malaysian Palm Oil Board has been extensively collected wild germplasm from its original area of 11 African countries which are Nigeria, Senegal, Gambia, Guinea, Sierra Leone, Ghana, Cameroon, Zaire, Angola, Madagascar, and Tanzania. The germplasm collections were established and maintained as a field gene bank in Malaysian Palm Oil Board (MPOB) Research Station in Kluang, Johor, Malaysia to conserve a wide range of oil palm genetic resources for genetic improvement of Malaysian oil palm industry. Therefore, assessing the performance and genetic diversity of the wild materials is very important for understanding the genetic structure of natural oil palm population and to explore genetic resources. Principal component analysis (PCA) and Cluster analysis are very efficient multivariate tools in the evaluation of genetic variation of germplasm and have been applied in many crops. In this study, eight populations of MPOB-Senegal oil palm germplasm were studied to explore the genetic variation pattern using PCA and cluster analysis. A total of 20 yield and yield component traits were used to analyze PCA and Ward’s clustering using SAS 9.4 version software. The first four principal components which have eigenvalue >1 accounted for 93% of total variation with the value of 44%, 19%, 18% and 12% respectively for each principal component. PC1 showed highest positive correlation with fresh fruit bunch (0.315), bunch number (0.321), oil yield (0.317), kernel yield (0.326), total economic product (0.324), and total oil (0.324) while PC 2 has the largest positive association with oil to wet mesocarp (0.397) and oil to fruit (0.458). The oil palm population were grouped into four distinct clusters based on 20 evaluated traits, this imply that high genetic variation existed in among the germplasm. Cluster 1 contains two populations which are SEN 12 and SEN 10, while cluster 2 has only one population of SEN 3. Cluster 3 consists of three populations which are SEN 4, SEN 6, and SEN 7 while SEN 2 and SEN 5 were grouped in cluster 4. Cluster 4 showed the highest mean value of fresh fruit bunch, bunch number, oil yield, kernel yield, total economic product, and total oil and Cluster 1 was characterized by high oil to wet mesocarp, and oil to fruit. The desired traits that have the largest positive correlation on extracted PCs could be utilized for the improvement of oil palm breeding program. The populations from different clusters with the highest cluster means could be used for hybridization. The information from this study can be utilized for effective conservation and selection of the MPOB-Senegal oil palm germplasm for the future breeding program.Keywords: cluster analysis, genetic variability, germplasm, oil palm, principal component analysis
Procedia PDF Downloads 1633876 Genetic Algorithm Optimization of Multiple Resources for Multi-Projects
Authors: A. Samer Ezeldin, Sarah A. Fotouh
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Optimization of resources is very important in all fields, as in construction management. Project managers have to face problems regarding management of cost, time and available resources of single projects and more problems arise when managing multiple projects. Most of the studies focused on optimization of resources for a single project, but, this paper will discuss the design and modeling of multiple resources optimization for multiple projects using Genetic Algorithm. Most of the companies in construction industry optimize the resources for single projects only, but with the presence of several mega projects in several developing countries running at the same time, there is a need for a model to enhance the efficiency of available resources and decreases the fluctuation as much as possible. The proposed model calculates the cost of each resource, tries to minimize the cost of extra resources as much as possible and generates the schedule of each project within a selected program.Keywords: construction management, genetic algorithm, multiple projects, multiple resources, optimization
Procedia PDF Downloads 4583875 Population Structure Analysis of Pakistani Indigenous Cattle Population by Using High Density SNP Array
Authors: Hamid Mustafa, Huson J. Heather, Kim Eiusoo, McClure Matt, Khalid Javed, Talat Nasser Pasha, Afzal Ali1, Adeela Ajmal, Tad Sonstegard
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Genetic differences associated with speciation, breed formation or local adaptation can help to preserve and effective utilization of animals in selection programs. Analyses of population structure and breed diversity have provided insight into the origin and evolution of cattle. In this study, we used a high-density panel of SNP markers to examine population structure and diversity among ten Pakistani indigenous cattle breeds. In total, 25 individuals from three cattle populations, including Achi (n=08), Bhagnari (n=04) and Cholistani (n=13) were genotyped for 777, 962 single nucleotide polymorphism (SNP) markers. Population structure was examined using the linkage model in the program STRUCTURE. After characterizing SNP polymorphism in the different populations, we performed a detailed analysis of genetic structure at both the individual and population levels. The whole-genome SNP panel identified several levels of population substructure in the set of examined cattle breeds. We further searched for spatial patterns of genetic diversity among these breeds under the recently developed spatial principal component analysis framework. Overall, such high throughput genotyping data confirmed a clear partitioning of the cattle genetic diversity into distinct breeds. The resulting complex historical origins associated with both natural and artificial selection have led to the differentiation of numerous different cattle breeds displaying a broad phenotypic variety over a short period of time.Keywords: Pakistan, cattle, genetic diversity, population structure
Procedia PDF Downloads 6193874 Curvelet Features with Mouth and Face Edge Ratios for Facial Expression Identification
Authors: S. Kherchaoui, A. Houacine
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This paper presents a facial expression recognition system. It performs identification and classification of the seven basic expressions; happy, surprise, fear, disgust, sadness, anger, and neutral states. It consists of three main parts. The first one is the detection of a face and the corresponding facial features to extract the most expressive portion of the face, followed by a normalization of the region of interest. Then calculus of curvelet coefficients is performed with dimensionality reduction through principal component analysis. The resulting coefficients are combined with two ratios; mouth ratio and face edge ratio to constitute the whole feature vector. The third step is the classification of the emotional state using the SVM method in the feature space.Keywords: facial expression identification, curvelet coefficient, support vector machine (SVM), recognition system
Procedia PDF Downloads 2313873 An Improved Genetic Algorithm for Traveling Salesman Problem with Precedence Constraint
Authors: M. F. F. Ab Rashid, A. N. Mohd Rose, N. M. Z. Nik Mohamed, W. S. Wan Harun, S. A. Che Ghani
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Traveling salesman problem with precedence constraint (TSPPC) is one of the most complex problems in combinatorial optimization. The existing algorithms to solve TSPPC cost large computational time to find the optimal solution. The purpose of this paper is to present an efficient genetic algorithm that guarantees optimal solution with less number of generations and iterations time. Unlike the existing algorithm that generates priority factor as chromosome, the proposed algorithm directly generates sequence of solution as chromosome. As a result, the proposed algorithm is capable of generating optimal solution with smaller number of generations and iteration time compare to existing algorithm.Keywords: traveling salesman problem, sequencing, genetic algorithm, precedence constraint
Procedia PDF Downloads 5573872 Estimation of Genetic Diversity in Sorghum Accessions Using Agro-Mophological and Nutritional Traits
Authors: Maletsema Alina Mofokeng, Nemera Shargie
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Sorghum is one of the most important cereal crops grown as a source of calories for many people in tropics and sub-tropics of the world. Proper characterisation and evaluation of crop germplasm is an important component for effective management of genetic resources and their utilisation in the improvement of the crop through plant breeding. The objective of the study was to estimate the genetic diversity present in sorghum accessions grown in South Africa using agro-morphological traits and some nutritional contents. The experiment was carried out in Potchefstroom. Data were subjected to correlations, principal components analysis, and hierarchical clustering using GenStat statistical software. There were highly significance differences among the accessions based on agro-morphological and nutritional quality traits. Grain yield was highly positively correlated with panicle weight. Plant height was highly significantly correlated with internode length, leaf length, leaf number, stem diameter, the number of nodes and starch content. The Principal component analysis revealed three most important PCs with a total variation of 78.6%. The protein content ranged from 7.7 to 14.7%, and starch ranged from 58.52 to 80.44%. The accessions that had high protein and starch content were AS16cyc and MP4277. There was vast genetic diversity observed among the accessions assessed that can be used by plant breeders to improve yield and nutritional traits.Keywords: accessions, genetic diversity, nutritional quality, sorghum
Procedia PDF Downloads 2613871 Prenatal Diagnosis of Beta Thalassemia Intermedia in Vietnamese Family: Case Report
Authors: Ha T. T. Ly, Truc B. Truc, Hai N. Truong, Mai P. T. Nguyen, Ngoc D. Ngo, Khanh V. Tran, Hai T. Le
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Beta thalassemia is one of the most common inherited blood disorders, which is characterized by decreased or absent in beta globin expression. Patients with Beta thalassemia whose anemia is not so severe as to necessitate transfusions are said to have thalassemia intermedia. Objective: The goal of this study is prenatal diagnosis for pregnancy woman with Beta thalassemia intermedia and her husband with Beta thalassemia carrier at high risk of Beta thalassemia major in Northern of Vietnam. Material and method: The family has a 6 years-old compound heterozygous thalassemia major for CD71/72(+A) and Hbb:c. -78A>G/nt-28(A>G) male child. The father was heterozygous for CD71/72(+A) mutation which is Beta plus type and the mother was compound heterozygosity of two different variants, namely, Hbb: c. -78A>G/nt-28(A>G) and CD26(A-G) HbE. Prenatal Beta thalassemia mutation detection in fetal DNA was carried out using multiplex Amplification-refractory mutation system ARMS-PCR and confirmed by direct Sanger-sequencing Hbb gene. Prenatal diagnoses were perfomed by amniotic fluid sampling from pregnant woman in the 16-18th week of pregnancy after the genotypes of parents of the probands were identified. Result: When amniotic fluid sample was analyzed for Beta globin gene (Hbb), we found that the genotype is heterozygous for CD71/72(+A) and CD26(A-G) HbE. This genotype is different from the 1st child of this family. Conclusion: Prenatal diagnosis helps the parents to know the genotype and the thalassemia status of the fetus, so they can have early decision on their pregnancy. Genetic diagnosis provided a useful method in diagnosis for familial members in pedigree, genetic counseling and prenatal diagnosis.Keywords: beta thalassemia intermedia, Hbb gene, pedigree, prenatal diagnosis
Procedia PDF Downloads 3813870 Study on Optimal Control Strategy of PM2.5 in Wuhan, China
Authors: Qiuling Xie, Shanliang Zhu, Zongdi Sun
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In this paper, we analyzed the correlation relationship among PM2.5 from other five Air Quality Indices (AQIs) based on the grey relational degree, and built a multivariate nonlinear regression equation model of PM2.5 and the five monitoring indexes. For the optimal control problem of PM2.5, we took the partial large Cauchy distribution of membership equation as satisfaction function. We established a nonlinear programming model with the goal of maximum performance to price ratio. And the optimal control scheme is given.Keywords: grey relational degree, multiple linear regression, membership function, nonlinear programming
Procedia PDF Downloads 2983869 Adaptive Programming for Indigenous Early Learning: The Early Years Model
Authors: Rachel Buchanan, Rebecca LaRiviere
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Context: The ongoing effects of colonialism continue to be experienced through paternalistic policies and funding processes that cause disjuncture between and across Indigenous early childhood programming on-reserve and in urban and Northern settings in Canada. While various educational organizations and social service providers have risen to address these challenges in the short, medium and long term, there continues to be a lack in nation-wide cohesive, culturally grounded, and meaningful early learning programming for Indigenous children in Canada. Indigenous-centered early learning programs tend to face one of two scaling dilemmas: their program goals are too prescriptive to enable the program to be meaningfully replicated in different cultural/ community settings, or their program goals are too broad to be meaningfully adapted to the unique cultural and contextual needs and desires of Indigenous communities (the “franchise approach”). There are over 600 First Nations communities in Canada representing more than 50 Nations and languages. Consequently, Indigenous early learning programming cannot be applied with a universal or “one size fits all” approach. Sustainable and comprehensive programming must be responsive to each community context, building upon existing strengths and assets to avoid program duplication and irrelevance. Thesis: Community-driven and culturally adapted early childhood programming is critical but cannot be achieved on a large scale within traditional program models that are constrained by prescriptive overarching program goals. Principles, rather than goals, are an effective way to navigate and evaluate complex and dynamic systems. Principles guide an intervention to be adaptable, flexible and scalable. The Martin Family Initiative (MFI) ’s Early Years program engages a principles-based approach to programming. As will be discussed in this paper, this approach enables the program to catalyze existing community-based strengths and organizational assets toward bridging gaps across and disjuncture between Indigenous early learning programs, as well as to scale programming in sustainable, context-responsive and dynamic ways. This paper argues that using a principles-driven and adaptive scaling approach, the Early Years model establishes important learnings for culturally adapted Indigenous early learning programming in Canada. Methodology: The Early Years has leveraged this approach to develop an array of programming with partner organizations and communities across the country. The Early Years began as a singular pilot project in one First Nation. In just three years, it has expanded to five different regions and community organizations. In each context, the program supports the partner organization through different means and to different ends, the extent to which is determined in partnership with each community-based organization: in some cases, this means supporting the organization to build home visiting programming from the ground-up; in others, it means offering organization-specific culturally adapted early learning resources to support the programming that already exists in communities. Principles underpin but do not define the practices of the program in each of these relationships. This paper will explore numerous examples of principles-based adaptability with the context of the Early Years, concluding that the program model offers theadaptability and dynamism necessary to respond to unique and ever-evolving community contexts and needs of Indigenous children today.Keywords: culturally adapted programming, indigenous early learning, principles-based approach, program scaling
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