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Sökning: db:Swepub > Linköpings universitet > Högskolan i Skövde

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11.
  • Badam, Tejaswi V. S., et al. (författare)
  • A validated generally applicable approach using the systematic assessment of disease modules by GWAS reveals a multi-omic module strongly associated with risk factors in multiple sclerosis
  • 2021
  • Ingår i: BMC Genomics. - : BioMed Central. - 1471-2164. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There exist few, if any, practical guidelines for predictive and falsifiable multi-omic data integration that systematically integrate existing knowledge. Disease modules are popular concepts for interpreting genome-wide studies in medicine but have so far not been systematically evaluated and may lead to corroborating multi-omic modules. Result: We assessed eight module identification methods in 57 previously published expression and methylation studies of 19 diseases using GWAS enrichment analysis. Next, we applied the same strategy for multi-omic integration of 20 datasets of multiple sclerosis (MS), and further validated the resulting module using both GWAS and risk-factor-associated genes from several independent cohorts. Our benchmark of modules showed that in immune-associated diseases modules inferred from clique-based methods were the most enriched for GWAS genes. The multi-omic case study using MS data revealed the robust identification of a module of 220 genes. Strikingly, most genes of the module were differentially methylated upon the action of one or several environmental risk factors in MS (n = 217, P = 10− 47) and were also independently validated for association with five different risk factors of MS, which further stressed the high genetic and epigenetic relevance of the module for MS. Conclusions: We believe our analysis provides a workflow for selecting modules and our benchmark study may help further improvement of disease module methods. Moreover, we also stress that our methodology is generally applicable for combining and assessing the performance of multi-omic approaches for complex diseases. 
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12.
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13.
  • Berg, Sofia, et al. (författare)
  • Using sensitivity analysis to identify keystone species and keystone links in size-based food webs
  • 2011
  • Ingår i: Oikos. - : Wiley. - 0030-1299 .- 1600-0706. ; 120:4, s. 510-519
  • Tidskriftsartikel (refereegranskat)abstract
    • Human-induced alterations in the birth and mortality rates of species and in the strength of interactions within and between species can lead to changes in the structure and resilience of ecological communities. Recent research points to the importance of considering the distribution of body sizes of species when exploring the response of communities to such perturbations. Here, we present a new size-based approach for assessing the sensitivity and elasticity of community structure (species equilibrium abundances) and resilience (rate of return to equilibrium) to changes in the intrinsic growth rate of species and in the strengths of species interactions. We apply this approach on two natural systems, the pelagic communities of the Baltic Sea and Lake Vättern, to illustrate how it can be used to identify potential keystone species and keystone links. We find that the keystone status of a species is closely linked to its body size. The analysis also suggests that communities are structurally and dynamically more sensitive to changes in the effects of prey on their consumers than in the effects of consumers on their prey. Moreover, we discuss how community sensitivity analysis can be used to study and compare the fragility of communities with different body size distributions by measuring the mean sensitivity or elasticity over all species or all interaction links in a community. We believe that the community sensitivity analysis developed here holds some promise for identifying species and links that are critical for the structural and dynamic robustness of ecological communities.
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14.
  • Billing, Erik, 1981-, et al. (författare)
  • Finding Your Way from the Bed to the Kitchen: Reenacting and Recombining Sensorimotor Episodes Learned from Human Demonstration
  • 2016
  • Ingår i: Frontiers in Robotics and Ai. - Lausanne, Switzerland : Frontiers Media SA. - 2296-9144. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Several simulation theories have been proposed as an explanation for how humans and other agents internalize an "inner world" that allows them to simulate interactions with the external real world - prospectively and retrospectively. Such internal simulation of interaction with the environment has been argued to be a key mechanism behind mentalizing and planning. In the present work, we study internal simulations in a robot acting in a simulated human environment. A model of sensory-motor interactions with the environment is generated from human demonstrations and tested on a Robosoft Kompai robot. The model is used as a controller for the robot, reproducing the demonstrated behavior. Information from several different demonstrations is mixed, allowing the robot to produce novel paths through the environment, toward a goal specified by top-down contextual information. The robot model is also used in a covert mode, where the execution of actions is inhibited and perceptions are generated by a forward model. As a result, the robot generates an internal simulation of the sensory-motor interactions with the environment. Similar to the overt mode, the model is able to reproduce the demonstrated behavior as internal simulations. When experiences from several demonstrations are combined with a top-down goal signal, the system produces internal simulations of novel paths through the environment. These results can be understood as the robot imagining an "inner world" generated from previous experience, allowing it to try out different possible futures without executing actions overtly. We found that the success rate in terms of reaching the specified goal was higher during internal simulation, compared to overt action. These results are linked to a reduction in prediction errors generated during covert action. Despite the fact that the model is quite successful in terms of generating covert behavior toward specified goals, internal simulations display different temporal distributions compared to their overt counterparts. Links to human cognition and specifically mental imagery are discussed.
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15.
  • Billing, Erik, PhD, 1981-, et al. (författare)
  • The DREAM Dataset : Supporting a data-driven study of autism spectrum disorder and robot enhanced therapy
  • 2020
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 15:8
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a dataset of behavioral data recorded from 61 children diagnosed with Autism Spectrum Disorder (ASD). The data was collected during a large-scale evaluation of Robot Enhanced Therapy (RET). The dataset covers over 3000 therapy sessions and more than 300 hours of therapy. Half of the children interacted with the social robot NAO supervised by a therapist. The other half, constituting a control group, interacted directly with a therapist. Both groups followed the Applied Behavior Analysis (ABA) protocol. Each session was recorded with three RGB cameras and two RGBD (Kinect) cameras, providing detailed information of children’s behavior during therapy. This public release of the dataset comprises body motion, head position and orientation, and eye gaze variables, all specified as 3D data in a joint frame of reference. In addition, metadata including participant age, gender, and autism diagnosis (ADOS) variables are included. We release this data with the hope of supporting further data-driven studies towards improved therapy methods as well as a better understanding of ASD in general.
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16.
  • Birtic, Martin, et al. (författare)
  • Towards ultra-flexibility : a framework for evaluating the cyber-physical continuum in flexible production systems
  • 2024
  • Ingår i: Procedia Computer Science. - : Elsevier. - 1877-0509. ; 232, s. 645-654, s. 645-654
  • Tidskriftsartikel (refereegranskat)abstract
    • Flexibility is often cited as a desirable key characteristic of modern production systems. In ultra-flexible production, machinery and layouts are in a constant state of adaptation to accommodate changing orders, varying products, or evolving conditions. Cyber-physical integration has been proposed as a potential approach to increasing system flexibility with Cyber-Physical Production Systems (CPPS) and Digital Twins (DT) as central concepts. While numerous architectures, frameworks and approaches have been proposed for CPPS and DT development, further research is motivated regarding the development of a requirement-based framework that links together the high-level system property of flexibility and lower-level system components, enabling the analysis, prescription and comparison of systems. Such a framework could enable manufacturers to continuously evaluate and improve manufacturing systems' flexibility as well as make informed design decisions. Ultimately enhancing system flexibility and responsiveness to changing production conditions. This study aims to initiate the development and formulation of such a requirements-based framework linking flexibility and lower-level system components. Additionally, it seeks to introduce the concept of a”cyber-physical continuum, ” which the study aims to define as a potential quantifiable indicator reflecting flexibility within production systems. This is achieved by leveraging prior CPPS research based on high-level system requirements. These requirements were expanded by branching each requirement into lower-level components creating a more granular scope and providing a finer lens for analysis and assessment. The framework was then applied to assess a high-mix, low-volume manufacturing scenario. Application of the preliminary framework in the case study indicates its potential utility in providing a useful view of the cyber-physical content of a system. Moreover, it serves as a valuable guide for pinpointing areas for improvement and development. By developing a framework that seamlessly links high-level flexibility requirements with detailed implementation requirements, systems can be comprehensively evaluated, methodically prescribed, and effectively compared. As future work, further refinement and validation of this framework will be crucial to ensuring its validity and applicability across diverse manufacturing contexts. 
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17.
  • Björn, Niclas, 1990-, et al. (författare)
  • Whole-genome sequencing and gene network modules predict gemcitabine/carboplatin-induced myelosuppression in non-small cell lung cancer patients
  • 2020
  • Ingår i: npj Systems Biology and Applications. - : Nature Publishing Group. - 2056-7189. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Gemcitabine/carboplatin chemotherapy commonly induces myelosuppression, including neutropenia, leukopenia, and thrombocytopenia. Predicting patients at risk of these adverse drug reactions (ADRs) and adjusting treatments accordingly is a long-term goal of personalized medicine. This study used whole-genome sequencing (WGS) of blood samples from 96 gemcitabine/carboplatin-treated non-small cell lung cancer (NSCLC) patients and gene network modules for predicting myelosuppression. Association of genetic variants in PLINK found 4594, 5019, and 5066 autosomal SNVs/INDELs with p ≤ 1 × 10−3 for neutropenia, leukopenia, and thrombocytopenia, respectively. Based on the SNVs/INDELs we identified the toxicity module, consisting of 215 unique overlapping genes inferred from MCODE-generated gene network modules of 350, 345, and 313 genes, respectively. These module genes showed enrichment for differentially expressed genes in rat bone marrow, human bone marrow, and human cell lines exposed to carboplatin and gemcitabine (p < 0.05). Then using 80% of the patients as training data, random LASSO reduced the number of SNVs/INDELs in the toxicity module into a feasible prediction model consisting of 62 SNVs/INDELs that accurately predict both the training and the test (remaining 20%) data with high (CTCAE 3–4) and low (CTCAE 0–1) maximal myelosuppressive toxicity completely, with the receiver-operating characteristic (ROC) area under the curve (AUC) of 100%. The present study shows how WGS, gene network modules, and random LASSO can be used to develop a feasible and tested model for predicting myelosuppressive toxicity. Although the proposed model predicts myelosuppression in this study, further evaluation in other studies is required to determine its reproducibility, usability, and clinical effect.
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18.
  • Borgmästars, Emmy, et al. (författare)
  • miRFA : an automated pipeline for microRNA functional analysis with correlation support from TCGA and TCPA expression data in pancreatic cancer
  • 2019
  • Ingår i: BMC Bioinformatics. - : BioMed Central. - 1471-2105. ; 20:1, s. 1-17
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: MicroRNAs (miRNAs) are small RNAs that regulate gene expression at a post-transcriptional level and are emerging as potentially important biomarkers for various disease states, including pancreatic cancer. In silico-based functional analysis of miRNAs usually consists of miRNA target prediction and functional enrichment analysis of miRNA targets. Since miRNA target prediction methods generate a large number of false positive target genes, further validation to narrow down interesting candidate miRNA targets is needed. One commonly used method correlates miRNA and mRNA expression to assess the regulatory effect of a particular miRNA. The aim of this study was to build a bioinformatics pipeline in R for miRNA functional analysis including correlation analyses between miRNA expression levels and its targets on mRNA and protein expression levels available from the cancer genome atlas (TCGA) and the cancer proteome atlas (TCPA). TCGA-derived expression data of specific mature miRNA isoforms from pancreatic cancer tissue was used.RESULTS: Fifteen circulating miRNAs with significantly altered expression levels detected in pancreatic cancer patients were queried separately in the pipeline. The pipeline generated predicted miRNA target genes, enriched gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGG) pathways. Predicted miRNA targets were evaluated by correlation analyses between each miRNA and its predicted targets. MiRNA functional analysis in combination with Kaplan-Meier survival analysis suggest that hsa-miR-885-5p could act as a tumor suppressor and should be validated as a potential prognostic biomarker in pancreatic cancer.CONCLUSIONS: Our miRNA functional analysis (miRFA) pipeline can serve as a valuable tool in biomarker discovery involving mature miRNAs associated with pancreatic cancer and could be developed to cover additional cancer types. Results for all mature miRNAs in TCGA pancreatic adenocarcinoma dataset can be studied and downloaded through a shiny web application at https://emmbor.shinyapps.io/mirfa/ .
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19.
  • Borrvall, Charlotte, et al. (författare)
  • Biodiversity lessens the risk of cascading extinction in model food webs
  • 2000
  • Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 3:2, s. 131-136
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to the complex interactions between species in food webs, the extinction of one species could lead to a cascade of further extinctions and hence cause dramatic changes in species composition and ecosystem processes. We found that the risk of additional species extinction, following the loss of one species in model food webs, decreases with the number of species per functional group. For a given number of species per functional group, the risk of further extinctions is highest when an autotroph is removed and lowest when a top predator is removed. In addition, stability decreases when the distribution of interaction strengths in the webs is changed from equal to skew (few strong and many weak links). We also found that omnivory appears to stabilize model food webs. Our results indicate that high biodiversity may serve as an insurance against radical ecosystem changes.
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20.
  • Bu, Huajie, et al. (författare)
  • Genotype < 21CAs/>= 21CAs and allele < 21CAs of the MANBA gene in melanoma risk and progression in a Swedish population
  • 2009
  • Ingår i: Molecular medicine reports. - : Spandidos Publications Ltd.. - 1791-2997 .- 1791-3004. ; 2:2, s. 259-263
  • Tidskriftsartikel (refereegranskat)abstract
    • Cutaneous melanoma is characterized by poor patient outcome in its later stages. The search for genetic markers is therefore crucial for the identification of populations at risk for melanoma. Highly polymorphic CA repeats in 3 proximity in the MANBA gene were examined by PCR-capillary electrophoresis in 185 Swedish melanoma patients and 441 tumor-free age- and gender-matched individuals. The associations of the polymorphisms with melanoma risk, the pigment phenotypes of the patients and tumor characteristics were analyzed. A significant difference in allelic distribution between melanoma patients and tumor-free individuals was observed. The frequency of the MANBA genotype <21CAs/>= 21CAs was significantly higher in melanoma patients than in the controls. When comparing allele distribution in patients and their matched controls, the allele <21 CAs was found to be associated with the female gender (39.8 vs. 31.2%, P=0.041, OR=1.46, 95% Cl 1.02-2.10), but not with male gender (34.4 vs. 30.9%, P=0.39). Within the melanoma group, there were no differences in the distribution of the MANBA alleles associated with patient gender or age before or after 55 years at diagnosis, nor was there any association between the MANBA genotype and pigment phenotype or tumor sites. The MANBA allele <21CAs was, however, associated with thin melanomas at diagnosis (Breslow thickness <= 1.5 mm and Clark levels I and II). In conclusion, these data suggest that MANBA polymorphisms might be an indicator of tumor growth and progression and, together with other markers, could be used to identify individuals at increased risk of melanoma.
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