| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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| 3. |
- Alenljung, Beatrice, 1971-, et al.
(författare)
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Conveying Emotions by Touch to the Nao Robot : A User Experience Perspective
- 2018
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Ingår i: Multimodal Technologies and Interaction. - : MDPI. - 2414-4088. ; 2:4
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Tidskriftsartikel (refereegranskat)abstract
- Social robots are expected gradually to be used by more and more people in a widerrange of settings, domestic as well as professional. As a consequence, the features and qualityrequirements on human–robot interaction will increase, comprising possibilities to communicateemotions, establishing a positive user experience, e.g., using touch. In this paper, the focus is ondepicting how humans, as the users of robots, experience tactile emotional communication with theNao Robot, as well as identifying aspects affecting the experience and touch behavior. A qualitativeinvestigation was conducted as part of a larger experiment. The major findings consist of 15 differentaspects that vary along one or more dimensions and how those influence the four dimensions ofuser experience that are present in the study, as well as the different parts of touch behavior ofconveying emotions.
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| 4. |
- Alenljung, Beatrice, et al.
(författare)
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User Experience of Conveying Emotions by Touch
- 2017
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Ingår i: Proceedings of the 26th IEEE International Symposium on Robot and Human Interactive Communication (RO-MAN). - : IEEE. - 9781538635179 - 9781538635193 - 9781538635186 ; , s. 1240-1247
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Konferensbidrag (refereegranskat)abstract
- In the present study, 64 users were asked to convey eight distinct emotion to a humanoid Nao robot via touch, and were then asked to evaluate their experiences of performing that task. Large differences between emotions were revealed. Users perceived conveying of positive/pro-social emotions as significantly easier than negative emotions, with love and disgust as the two extremes. When asked whether they would act differently towards a human, compared to the robot, the users’ replies varied. A content analysis of interviews revealed a generally positive user experience (UX) while interacting with the robot, but users also found the task challenging in several ways. Three major themes with impact on the UX emerged; responsiveness, robustness, and trickiness. The results are discussed in relation to a study of human-human affective tactile interaction, with implications for human-robot interaction (HRI) and design of social and affective robotics in particular.
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| 5. |
- Andreasson, Rebecca, et al.
(författare)
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Affective Touch in Human-Robot Interaction: Conveying Emotion to the Nao Robot
- 2018
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Ingår i: International Journal of Social Robotics. - : Springer Science and Business Media LLC. - 1875-4791 .- 1875-4805. ; 10:4, s. 473-491
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Tidskriftsartikel (refereegranskat)abstract
- Affective touch has a fundamental role in human development, social bonding, and for providing emotional support in interpersonal relationships. We present, what is to our knowledge, the first HRI study of tactile conveyance of both positive and negative emotions (affective touch) on the Nao robot, and based on an experimental set-up from a study of human-human tactile communication. In the present work, participants conveyed eight emotions to a small humanoid robot via touch. We found that female participants conveyed emotions for a longer time, using more varied interaction and touching more regions on the robot's body, compared to male participants. Several differences between emotions were found such that emotions could be classified by the valence of the emotion conveyed, by combining touch amount and duration. Overall, these results show high agreement with those reported for human-human affective tactile communication and could also have impact on the design and placement of tactile sensors on humanoid robots.
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| 6. |
- Bedford, Lynn, et al.
(författare)
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Depletion of 26S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies
- 2008
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 28:33, s. 8189-98
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Tidskriftsartikel (refereegranskat)abstract
- Ubiquitin-positive intraneuronal inclusions are a consistent feature of the major human neurodegenerative diseases, suggesting that dysfunction of the ubiquitin proteasome system is central to disease etiology. Research using inhibitors of the 20S proteasome to model Parkinson's disease is controversial. We report for the first time that specifically 26S proteasomal dysfunction is sufficient to trigger neurodegenerative disease. Here, we describe novel conditional genetic mouse models using the Cre/loxP system to spatially restrict inactivation of Psmc1 (Rpt2/S4) to neurons of either the substantia nigra or forebrain (e.g., cortex, hippocampus, and striatum). PSMC1 is an essential subunit of the 26S proteasome and Psmc1 conditional knock-out mice display 26S proteasome depletion in targeted neurons, in which the 20S proteasome is not affected. Impairment of specifically ubiquitin-mediated protein degradation caused intraneuronal Lewy-like inclusions and extensive neurodegeneration in the nigrostriatal pathway and forebrain regions. Ubiquitin and alpha-synuclein neuropathology was evident, similar to human Lewy bodies, but interestingly, inclusion bodies contained mitochondria. We support this observation by demonstrating mitochondria in an early form of Lewy body (pale body) from Parkinson's disease patients. The results directly confirm that 26S dysfunction in neurons is involved in the pathology of neurodegenerative disease. The model demonstrates that 26S proteasomes are necessary for normal neuronal homeostasis and that 20S proteasome activity is insufficient for neuronal survival. Finally, we are providing the first reproducible genetic platform for identifying new therapeutic targets to slow or prevent neurodegeneration.
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| 7. |
- Lowe, Robert, 1975-, et al.
(författare)
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Designing for a Wearable Affective Interface for the NAO Robot : A Study of Emotion Conveyance by Touch
- 2018
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Ingår i: Multimodal Technologies and Interaction. - : M D P I AG. - 2414-4088. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- We here present results and analysis from a study of affective tactile communication between human and humanoid robot (the NAO robot). In the present work, participants conveyed eight emotions to the NAO via touch. In this study, we sought to understand the potential for using a wearable affective (tactile) interface, or WAffI. The aims of our study were to address the following: (i) how emotions and affective states can be conveyed (encoded) to such a humanoid robot, (ii) what are the effects of dressing the NAO in the WAffI on emotion conveyance and (iii) what is the potential for decoding emotion and affective states. We found that subjects conveyed touch for longer duration and over more locations on the robot when the NAO was dressed with WAffI than when it was not. Our analysis illuminates ways by which affective valence, and separate emotions, might be decoded by a humanoid robot according to the different features of touch: intensity, duration, location, type. Finally, we discuss the types of sensors and their distribution as they may be embedded within the WAffI and that would likely benefit Human-NAO (and Human-Humanoid) interaction along the affective tactile dimension.
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| 8. |
- O'Boyle, Noel, et al.
(författare)
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Open Data, Open Source and Open Standards in chemistry : The Blue Obelisk five years on
- 2011
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Ingår i: Journal of Cheminformatics. - : BioMed Central. - 1758-2946. ; 3, s. 37-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Blue Obelisk movement was established in 2005 as a response to the lack of Open Data,Open Standards and Open Source (ODOSOS) in chemistry. It aims to make it easier to carry out chemistryresearch by promoting interoperability between chemistry software, encouraging cooperation between OpenSource developers, and developing community resources and Open Standards. Results: This contribution looks back on the work carried out by the Blue Obelisk in the past 5 years and surveysprogress and remaining challenges in the areas of Open Data, Open Standards, and Open Source in chemistry. Conclusions: We show that the Blue Obelisk has been very successful in bringing together researchers anddevelopers with common interests in ODOSOS, leading to development of many useful resources freely availableto the chemistry community
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| 9. |
- Párniczky, Andrea, et al.
(författare)
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EPC/HPSG evidence-based guidelines for the management of pediatric pancreatitis.
- 2018
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Ingår i: Pancreatology (Print). - : Elsevier BV. - 1424-3903 .- 1424-3911. ; 18:2, s. 146-160
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pediatric pancreatitis is an underdiagnosed disease with variable etiology. In the past 10-15 years the incidence of pediatric pancreatitis has increased, it is now 3.6-13.3 cases per 100,000 children. Up-to-date evidence based management guidelines are lacking for the pediatric pancreatitis. The European Pancreatic Club, in collaboration with the Hungarian Pancreatic Study Group organized a consensus guideline meeting on the diagnosis and management of pancreatitis in the pediatric population.METHODS: Pediatric Pancreatitis was divided into three main clinical categories: acute pancreatitis, acute recurrent pancreatitis and chronic pancreatitis. Fifteen relevant topics (acute pancreatitis: diagnosis; etiology; prognosis; imaging; complications; therapy; biliary tract management; acute recurrent pancreatitis: diagnosis; chronic pancreatitis: diagnosis, etiology, treatment, imaging, intervention, pain, complications; enzyme replacement) were defined. Ten experts from the USA and Europe reviewed and summarized the available literature. Evidence was classified according to the GRADE classification system.RESULTS: Within fifteen topics, forty-seven relevant clinical questions were defined. The draft of the updated guideline was presented and discussed at the consensus meeting held during the 49th Meeting of European Pancreatic Club, in Budapest, on July 1, 2017.CONCLUSIONS: These evidence-based guidelines provides the current state of the art of the diagnosis and management of pediatric pancreatitis.
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| 10. |
- Wieduwilt, Matthew J., et al.
(författare)
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Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia
- 2022
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:1, s. 339-357
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Tidskriftsartikel (refereegranskat)abstract
- The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLAmatched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P <_ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P <_ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (<_18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.
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