Algorítmos heurísticos para el problema del Set Covering: mejora mediante aleatorización

Los métodos heurísticos pretenden resolver problemas de optimización proporcionando soluciones factibles que, aunque no optimicen la función objetivo, se acercan mucho al valor óptimo empleando un tiempo más que razonable. En esta memoria se va a resolver el problema del Set Covering y para conseguirlo usamos algoritmos heurísticos que consisten en la combinación de un método greedy y un algoritmo de mejora, basados en dos ideas principalmente, la diversificación y la intensificación, la primera se lleva a cabo mediante la aleatorización y la segunda mediante la búsqueda local. Se estudia cómo la introducción de aleatorización, de diferentes formas, en los métodos greedy hace que mejore sustancialmente los resultados y se emplee un menor tiempo que el de los algoritmos exactos.Grado en Estadístic

Using next-generation DNA sequence data for genetic association tests based on allele counts with and without consideration of zero inflation

The relationship between genetic variability and individual phenotypes is usually investigated by testing for association relying on called genotypes. Allele counts obtained from next-generation sequence data could be used for this purpose too. Genetic association can be examined by treating alternative allele counts (AACs) as the response variable in negative binomial regression. AACs from sequence data often contain an excess of zeros, thus motivating the use of Hurdle and zero-inflated models. Here we examine rough type I error rates and the ability to pick out variants with small probability values for 7 different testing approaches that incorporate AACs as an explanatory or as a response variable. Model comparisons relied on chromosome 3 DNA sequence data from 407 Hispanic participants in the Type 2 Diabetes Genetic Exploration by Next-generation sequencing in Ethnic Samples (T2D-GENES) project 1 with complete information on diastolic blood pressure and related medication. Our results suggest that in the investigation of the relationship between AAC as response variable and individual phenotypes as explanatory variable, Hurdle-negative binomial regression has some advantages. This model showed a good ability to discriminate strongly associated variants and controlled overall type I error rates. However, probability values from Hurdle-negative binomial regression were not obtained for approximately 25 % of the investigated variants because of convergence problems, and the mass of the probability value distribution was concentrated around 1

Chlorophyll fluorescence emission of tomato plants as a response to pulsed light based LEDs

The effects of pulsed light based-LEDs at eleven frequencies (0.1, 1, 10, 50, 100, 500 Hz, 1, 5, 10, 50 and 100 kHz) programmed at 50 % duty cycle were analyzed, obtaining important parameters of the fluorescence emission of chlorophyll such as: maximum fluorescence (Fm0), minimum fluorescence, the fluorescence emission in steady state, maximum efficiency of PSII (Fv0/Fm0), the fraction of PSII centers that are open, photochemical quenching, nonphotochemical quenching (NPQ), quantum efficiency of photosystem II (UPSII), electron transport rate (ETR) and quantum yield of CO2 assimilation (/CO2). For the study and validation of the results obtained in the experiments, the analysis of variance (ANOVA) was applied 0for each parameter with confidence intervals of 95 %. The results show that the frequencies of pulsed light had positive and negative effects on the fluorescence parameters with respect to the control treatment (continuous light). The frequencies that generated the best performance of Fv0/Fm0, NPQ, UPSII, ETR, /CO2 in tomato plants were 0.1, 1, 100 Hz, and 1 kHz. The increase obtained in these parameters can represent an optimal growth and productivity conditions for optimal energy consumption

miR-16 and miR-125b are involved in barrier function dysregulation through the modulation of claudin-2 and cingulin expression in the jejunum in IBS with diarrhoea

Micro-RNAs (miRNAs) play a crucial role in controlling intestinal epithelial barrier function partly by modulating the expression of tight junction (TJ) proteins. We have previously shown differential messenger RNA (mRNA) expression correlated with ultrastructural abnormalities of the epithelial barrier in patients with diarrhoea-predominant IBS (IBS-D). However, the participation of miRNAs in these differential mRNA-associated findings remains to be established. Our aims were (1) to identify miRNAs differentially expressed in the small bowel mucosa of patients with IBS-D and (2) to explore putative target genes specifically involved in epithelial barrier function that are controlled by specific dysregulated IBS-D miRNAs. Healthy controls and patients meeting Rome III IBS-D criteria were studied. Intestinal tissue samples were analysed to identify potential candidates by: (a) miRNA-mRNA profiling; (b) miRNA-mRNA pairing analysis to assess the co-expression profile of miRNA-mRNA pairs; (c) pathway analysis and upstream regulator identification; (d) miRNA and target mRNA validation. Candidate miRNA-mRNA pairs were functionally assessed in intestinal epithelial cells. IBS-D samples showed distinct miRNA and mRNA profiles compared with healthy controls. TJ signalling was associated with the IBS-D transcriptional profile. Further validation of selected genes showed consistent upregulation in 75% of genes involved in epithelial barrier function. Bioinformatic analysis of putative miRNA binding sites identified hsa-miR-125b-5p and hsa-miR-16 as regulating expression of the TJ genes CGN (cingulin) and CLDN2 (claudin-2), respectively. Consistently, protein expression of CGN and CLDN2 was upregulated in IBS-D, while the respective targeting miRNAs were downregulated. In addition, bowel dysfunction, perceived stress and depression and number of mast cells correlated with the expression of hsa-miR-125b-5p and hsa-miR-16 and their respective target proteins. Modulation of the intestinal epithelial barrier function in IBS-D involves both transcriptional and post-transcriptional mechanisms. These molecular mechanisms include miRNAs as master regulators in controlling the expression of TJ proteins and are associated with major clinical symptoms

Chlorophyll fluorescence emission as a response of pulsed light based-leds in tomato plants

The effects of pulsed light based-LEDs at eleven frequencies (0.1, 1, 10, 50, 100, 500 Hz, 1, 5, 10, 50 and 100 kHz) programmed at 50 % duty cycle were analyzed, obtaining important parameters of the fluorescence emission of chlorophyll such as: maximum fluorescence (Fm0), minimum fluorescence, the fluorescence emission in steady state, maximum efficiency of PSII (Fv0/Fm0), the fraction of PSII centers that are open, photochemical quenching, nonphotochemical quenching (NPQ), quantum efficiency of photosystem II (UPSII), electron transport rate (ETR) and quantum yield of CO2 assimilation (/CO2). For the study and validation of the results obtained in the experiments, the analysis of variance (ANOVA) was applied 0for each parameter with confidence intervals of 95 %

Chlorophyll fluorescence emission as a response of pulsed light based-leds in tomato plants

The effects of pulsed light based-LEDs at eleven frequencies (0.1, 1, 10, 50, 100, 500 Hz, 1, 5, 10, 50 and 100 kHz) programmed at 50 % duty cycle were analyzed, obtaining important parameters of the fluorescence emission of chlorophyll such as: maximum fluorescence (Fm0), minimum fluorescence, the fluorescence emission in steady state, maximum efficiency of PSII (Fv0/Fm0), the fraction of PSII centers that are open, photochemical quenching, nonphotochemical quenching (NPQ), quantum efficiency of photosystem II (UPSII), electron transport rate (ETR) and quantum yield of CO2 assimilation (/CO2). For the study and validation of the results obtained in the experiments, the analysis of variance (ANOVA) was applied 0for each parameter with confidence intervals of 95 %

RNA Sequencing of Hepatobiliary Cancer Cell Lines: Data and Applications to Mutational and Transcriptomic Profiling

Cancer cell lines allow the identification of clinically relevant alterations and the prediction of drug response. However, sequencing data for hepatobiliary cancer cell lines in general, and particularly gallbladder cancer (GBC), are sparse. Here, we apply RNA sequencing to characterize 10 GBC, eight hepatocellular carcinoma, and five cholangiocarcinoma (CCA) cell lines. RNA extraction, quality control, library preparation, sequencing, and pre-processing of sequencing data were implemented using state-of-the-art techniques. Public data from the MSK-IMPACT database and a large cohort of Japanese biliary tract cancer patients were used to illustrate the usage of the released data. The total number of exonic mutations varied from 7207 for the cell line NOZ to 9760 for HuCCT1. Researchers planning experiments that require TP53 mutations could use the cell lines NOZ, OCUG-1, SNU308, or YoMi. Mz-Cha-1 showed mutations in ATM, SNU308 presented SMAD4 mutations, and the only investigated cell line that showed ARID1A mutations was GB-d1. SNU478 was the cell line with the global gene expression pattern most similar to GBC, intrahepatic CCA, and extrahepatic CCA. EGFR, KMT2D, and KMT2C generally presented a higher expression in the investigated cell lines than in Japanese primary GBC tumors. We provide the scientific community with detailed mutation and gene expression data, together with three showcase applications, with the aim of facilitating the design of future in vitro cell culture assays for research on hepatobiliary cancer

miR-16 and miR-125b are involved in barrier function dysregulation through the modulation of claudin-2 and cingulin expression in the jejunum in IBS with diarrhoea

Micro-RNAs (miRNAs) play a crucial role in controlling intestinal epithelial barrier function partly by modulating the expression of tight junction (TJ) proteins. We have previously shown differential messenger RNA (mRNA) expression correlated with ultrastructural abnormalities of the epithelial barrier in patients with diarrhoea-predominant IBS (IBS-D). However, the participation of miRNAs in these differential mRNA-associated findings remains to be established. Our aims were (1) to identify miRNAs differentially expressed in the small bowel mucosa of patients with IBS-D and (2) to explore putative target genes specifically involved in epithelial barrier function that are controlled by specific dysregulated IBS-D miRNAs. Healthy controls and patients meeting Rome III IBS-D criteria were studied. Intestinal tissue samples were analysed to identify potential candidates by: (a) miRNA-mRNA profiling; (b) miRNA-mRNA pairing analysis to assess the co-expression profile of miRNA-mRNA pairs; (c) pathway analysis and upstream regulator identification; (d) miRNA and target mRNA validation. Candidate miRNA-mRNA pairs were functionally assessed in intestinal epithelial cells. IBS-D samples showed distinct miRNA and mRNA profiles compared with healthy controls. TJ signalling was associated with the IBS-D transcriptional profile. Further validation of selected genes showed consistent upregulation in 75% of genes involved in epithelial barrier function. Bioinformatic analysis of putative miRNA binding sites identified hsa-miR-125b-5p and hsa-miR-16 as regulating expression of the TJ genes CGN (cingulin) and CLDN2 (claudin-2), respectively. Consistently, protein expression of CGN and CLDN2 was upregulated in IBS-D, while the respective targeting miRNAs were downregulated. In addition, bowel dysfunction, perceived stress and depression and number of mast cells correlated with the expression of hsa-miR-125b-5p and hsa-miR-16 and their respective target proteins. Modulation of the intestinal epithelial barrier function in IBS-D involves both transcriptional and post-transcriptional mechanisms. These molecular mechanisms include miRNAs as master regulators in controlling the expression of TJ proteins and are associated with major clinical symptoms