Search results for "model."
showing 10 items of 23664 documents
Search for a Minimal Set of Parameters by Assessing the Total Optimization Potential for a Dynamic Model of a Biochemical Network.
2017
Selecting an efficient small set of adjustable parameters to improve metabolic features of an organism is important for a reduction of implementation costs and risks of unpredicted side effects. In practice, to avoid the analysis of a huge combinatorial space for the possible sets of adjustable parameters, experience-, and intuition-based subsets of parameters are often chosen, possibly leaving some interesting counter-intuitive combinations of parameters unrevealed. The combinatorial scan of possible adjustable parameter combinations at the model optimization level is possible; however, the number of analyzed combinations is still limited. The total optimization potential (TOP) approach is…
A Dirichlet Autoregressive Model for the Analysis of Microbiota Time-Series Data
2021
Growing interest in understanding microbiota dynamics has motivated the development of different strategies to model microbiota time series data. However, all of them must tackle the fact that the available data are high-dimensional, posing strong statistical and computational challenges. In order to address this challenge, we propose a Dirichlet autoregressive model with time-varying parameters, which can be directly adapted to explain the effect of groups of taxa, thus reducing the number of parameters estimated by maximum likelihood. A strategy has been implemented which speeds up this estimation. The usefulness of the proposed model is illustrated by application to a case study.
EGFL7 enhances surface expression of integrin α5β1 to promote angiogenesis in malignant brain tumors
2018
Abstract Glioblastoma (GBM) is a typically lethal type of brain tumor with a median survival of 15 months postdiagnosis. This negative prognosis prompted the exploration of alternative treatment options. In particular, the reliance of GBM on angiogenesis triggered the development of anti‐VEGF (vascular endothelial growth factor) blocking antibodies such as bevacizumab. Although its application in human GBM only increased progression‐free periods but did not improve overall survival, physicians and researchers still utilize this treatment option due to the lack of adequate alternatives. In an attempt to improve the efficacy of anti‐VEGF treatment, we explored the role of the egfl7 gene in ma…
Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo chronic myelogenous Leukemia cell growth
2017
Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered. There is, therefore, urgent need to develop alternative strategies to overcome drug resistance. According to the molecules expressed on their surface, exosomes can target specific cells. Exosomes can also be loaded with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents. In this study, we engineered HEK293T cells to express the exosomal protein Lamp2b, fused to a fragment of Interleukin 3 (IL3). The IL3 receptor (IL3-R) is overexpressed in CML…
Dairy product consumption and risk of type 2 diabetes in an elderly Spanish Mediterranean population at high cardiovascular risk.
2015
PURPOSE The possible effects of dairy consumption on diabetes prevention remain controversial. The aim of this study was to investigate the association between the dairy consumption and type 2 diabetes (T2D) risk in an elderly Mediterranean population at high cardiovascular risk. METHODS: We prospectively followed 3,454 non-diabetic individuals from the PREDIMED study. Dairy consumption was assessed at baseline and yearly using food frequency questionnaires and categorized into total, low-fat, whole-fat, and subgroups: milk, yogurt, cheeses, fermented dairy, concentrated full fat, and processed dairy. Hazard ratios (HRs) were calculated using Cox proportional hazards regression models. RESU…
A 13 mer LNA-i-miR-221 Inhibitor Restores Drug Sensitivity in Melphalan-Refractory Multiple Myeloma Cells.
2016
Abstract Purpose: The onset of drug resistance is a major cause of treatment failure in multiple myeloma. Although increasing evidence is defining the role of miRNAs in mediating drug resistance, their potential activity as drug-sensitizing agents has not yet been investigated in multiple myeloma. Experimental Design: Here we studied the potential utility of miR-221/222 inhibition in sensitizing refractory multiple myeloma cells to melphalan. Results: miR-221/222 expression inversely correlated with melphalan sensitivity of multiple myeloma cells. Inhibition of miR-221/222 overcame melphalan resistance and triggered apoptosis of multiple myeloma cells in vitro, in the presence or absence of…
The interplay between genetic and bioelectrical signaling permits a spatial regionalisation of membrane potentials in model multicellular ensembles
2016
AbstractThe single cell-centred approach emphasises ion channels as specific proteins that determine individual properties, disregarding their contribution to multicellular outcomes. We simulate the interplay between genetic and bioelectrical signals in non-excitable cells from the local single-cell level to the long range multicellular ensemble. The single-cell genetic regulation is based on mean-field kinetic equations involving the mRNA and protein concentrations. The transcription rate factor is assumed to depend on the absolute value of the cell potential, which is dictated by the voltage-gated cell ion channels and the intercellular gap junctions. The interplay between genetic and ele…
Cell-cell bioelectrical interactions and local heterogeneities in genetic networks: a model for the stabilization of single-cell states and multicell…
2018
Genetic networks operate in the presence of local heterogeneities in single-cell transcription and translation rates. Bioelectrical networks and spatio-temporal maps of cell electric potentials can influence multicellular ensembles. Could cell-cell bioelectrical interactions mediated by intercellular gap junctions contribute to the stabilization of multicellular states against local genetic heterogeneities? We theoretically analyze this question on the basis of two well-established experimental facts: (i) the membrane potential is a reliable read-out of the single-cell electrical state and (ii) when the cells are coupled together, their individual cell potentials can be influenced by ensemb…
Early Cognitive Training Rescues Remote Spatial Memory but Reduces Cognitive Flexibility in Alzheimer’s Disease Mice
2020
Background: Spatial memory dysfunction has been demonstrated in mouse models of Alzheimer’s disease (AD) which is consistent with the clinical finding that the early signature of AD includes difficulties in the formation and/or storage of a memory. A stored memory—a long term memory—can be modulated via process called as memory retrieval that can either lead toward memory reconsolidation or even memory extinction. Objective: We aim to shed light on the fate of the spatial memory during memory reactivation and memory extinction using a water maze task. Methods: In Set-up I, we trained 3-month-old mice (wild-type mice and mice with cerebral β-amyloidosis) and assessed the fate of remote memor…
Drosophila melanogaster Models of Metal-Related Human Diseases and Metal Toxicity
2017
Iron, copper and zinc are transition metals essential for life because they are required in a multitude of biological processes. Organisms have evolved to acquire metals from nutrition and to maintain adequate levels of each metal to avoid damaging effects associated with its deficiency, excess or misplacement. Interestingly, the main components of metal homeostatic pathways are conserved, with many orthologues of the human metal-related genes having been identified and characterized in Drosophila melanogaster. Drosophila has gained appreciation as a useful model for studying human diseases, including those caused by mutations in pathways controlling cellular metal homeostasis. Flies have m…