| 1. |
- Barrio, Alvaro Martinez, et al.
(författare)
-
Targeted Resequencing and Analysis of the Diamond-Blackfan Anemia Disease Locus RPS19
- 2009
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:7, s. e6172-
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Ribosomal protein S19 gene locus (RPS19) has been linked to two kinds of red cell aplasia, Diamond-Blackfan Anemia (DBA) and Transient Erythroblastopenia in Childhood (TEC). Mutations in RPS19 coding sequences have been found in 25% of DBA patients, but not in TEC patients. It has been suggested that non-coding RPS19 sequence variants contribute to the considerable clinical variability in red cell aplasia. We therefore aimed at identifying non-coding variations associated with DBA or TEC phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: We targeted a region of 19'980 bp encompassing the RPS19 gene in a cohort of 89 DBA and TEC patients for resequencing. We provide here a catalog of the considerable, previously unrecognized degree of variation in this region. We identified 73 variations (65 SNPs, 8 indels) that all are located outside of the RPS19 open reading frame, and of which 67.1% are classified as novel. We hypothesize that specific alleles in non-coding regions of RPS19 could alter the binding of regulatory proteins or transcription factors. Therefore, we carried out an extensive analysis to identify transcription factor binding sites (TFBS). A series of putative interaction sites coincide with detected variants. Sixteen of the corresponding transcription factors are of particular interest, as they are housekeeping genes or show a direct link to hematopoiesis, tumorigenesis or leukemia (e.g. GATA-1/2, PU.1, MZF-1). CONCLUSIONS: Specific alleles at predicted TFBSs may alter the expression of RPS19, modify an important interaction between transcription factors with overlapping TFBS or remove an important stimulus for hematopoiesis. We suggest that the detected interactions are of importance for hematopoiesis and could provide new insights into individual response to treatment.
|
|
| 2. |
- Dahl, Oskar, et al.
(författare)
-
Understanding Association Between Logged Vehicle Data and Vehicle Marketing Parameters : Using Clustering and Rule-Based Machine Learning
- 2020
-
Ingår i: Proceedings of the 2020 3rd International Conference on Information Management and Management Science, IMMS 2020. - New York : Association for Computing Machinery (ACM). - 9781450375467 ; , s. 13-22
-
Konferensbidrag (refereegranskat)abstract
- Trucks are designed, configured and marketed for various working environments. There lies a concern whether trucks are used as intended by the manufacturer, as usage may impact the longevity, efficiency and productivity of the trucks. In this paper we propose a framework that aims to extract costumers' vehicle behaviours from Logged Vehicle Data (LVD) in order to evaluate whether they align with vehicle configurations, so-called Global Transport Application (GTA) parameters. Gaussian mixture model (GMM)s are employed to cluster and classify various vehicle behaviors from the LVD. Rule-based machine learning (RBML) was applied on the clusters to examine whether vehicle behaviors follow the GTA configuration. Particularly, we propose an approach based on studying associations that is able to extract insights on whether the trucks are used as intended. Experimental results shown that while for the vast majority of the trucks' behaviors seemingly follows their GTA configuration, there are also interesting outliers that warrant further analysis. © 2020 ACM.
|
|
| 3. |
- Fischer, Johannes, et al.
(författare)
-
Observer agreement of imaging measurements used for evaluation of dentofacial deformity in juvenile idiopathic arthritis
- 2022
-
Ingår i: Dento-Maxillo-Facial Radiology. - : British Institute of Radiology. - 0250-832X .- 1476-542X. ; 51:6
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives:To examine the precision of imaging measures commonly used to assess mandibular morphology in children and adolescents with juvenile idiopathic arthritis (JIA). Secondly, to compare cone-beam computed tomography (CBCT) and magnetic resonance imaging (MRI) in the measurement of condylar height.Methods:Those included were children diagnosed with JIA during 2015–18 who had had an MRI, a CBCT of the temporomandibular joints (TMJs) and a lateral cephalogram (ceph) of the head within one month of each other. Agreement within and between observers and methods was examined using Bland-Altman mean-difference plots and 95% limits of agreement (LOA). A 95% LOA within 15% of the sample mean was considered acceptable. Minimal detectable change (MDC) within and between observers was estimated.Results:90 patients (33 males) were included, with a mean age of 12.8 years. For MRI, intra- and interobserver 95% LOA were relatively narrow for total mandibular length: 9.6% of the sample mean. For CBCT, condylar height, both intra- and interobserver 95% LOA were wide: 16.0 and 28.4% of the sample mean, respectively. For ceph, both intra- and interobserver 95% LOA were narrow for the SNA-angle and gonion angle: 5.9 and 8% of the sample mean, and 6.2 and 6.8%, respectively.Conclusions:We have identified a set of precise measurements for facial morphology assessments in JIA, including one MRI-based (total mandibular length), one CBCT-based (condylar height), and three ceph-based. Condylar height was higher for MRI than for CBCT; however, the measurement was too imprecise for clinical use. MDC was also determined for a series of measurements.
|
|
| 4. |
- Flygare, Oskar, et al.
(författare)
-
Adapted cognitive behavior therapy for obsessive-compulsive disorder with co-occurring autism spectrum disorder : A clinical effectiveness study
- 2020
-
Ingår i: Autism. - : SAGE Publications. - 1362-3613 .- 1461-7005. ; 24:1, s. 190-199
-
Tidskriftsartikel (refereegranskat)abstract
- Obsessive-compulsive disorder and autism spectrum disorder commonly co-occur. Adapted cognitive behavior therapy for obsessive-compulsive disorder in adults with autism spectrum disorder has not previously been evaluated outside the United Kingdom. In this study, 19 adults with obsessive-compulsive disorder and autism spectrum disorder were treated using an adapted cognitive behavior therapy protocol that consisted of 20 sessions focused on exposure with response prevention. The primary outcome was the clinician-rated Yale-Brown Obsessive-Compulsive Scale. Participants were assessed up to 3 months after treatment. There were significant reductions on the Yale-Brown Obsessive-Compulsive Scale at post-treatment (d = 1.5), and improvements were sustained at follow-up (d = 1.2). Self-rated obsessive-compulsive disorder and depressive symptoms showed statistically significant reductions. Improvements in general functioning and quality of life were statistically non-significant. Three participants (16%) were responders at post-treatment and four (21%) were in remission from obsessive-compulsive disorder. At follow-up, three participants (16%) were responders and one (5%) was in full remission. Adapted cognitive behavior therapy for obsessive-compulsive disorder in adults with co-occurring autism spectrum disorder is associated with reductions in obsessive-compulsive symptoms and depressive symptoms. However, outcomes are modest; few patients were completely symptom free, and treatment engagement was low with few completed exposures and low adherence to homework assignments. We identify and discuss the need for further treatment refinement for this vulnerable group.
|
|
| 5. |
- Ghosh, Swagatha, et al.
(författare)
-
A simple goniometer-compatible flow cell for serial synchrotron X-ray crystallography
- 2023
-
Ingår i: Journal of Applied Crystallography. - 0021-8898. ; 56:Pt 2, s. 449-460
-
Tidskriftsartikel (refereegranskat)abstract
- Serial femtosecond crystallography was initially developed for room-temperature X-ray diffraction studies of macromolecules at X-ray free electron lasers. When combined with tools that initiate biological reactions within microcrystals, time-resolved serial crystallography allows the study of structural changes that occur during an enzyme catalytic reaction. Serial synchrotron X-ray crystallography (SSX), which extends serial crystallography methods to synchrotron radiation sources, is expanding the scientific community using serial diffraction methods. This report presents a simple flow cell that can be used to deliver microcrystals across an X-ray beam during SSX studies. This device consists of an X-ray transparent glass capillary mounted on a goniometer-compatible 3D-printed support and is connected to a syringe pump via lightweight tubing. This flow cell is easily mounted and aligned, and it is disposable so can be rapidly replaced when blocked. This system was demonstrated by collecting SSX data at MAX IV Laboratory from microcrystals of the integral membrane protein cytochrome c oxidase from Thermus thermophilus, from which an X-ray structure was determined to 2.12 Å resolution. This simple SSX platform may help to lower entry barriers for non-expert users of SSX.
|
|
| 6. |
- Hamon, Camille, et al.
(författare)
-
Sector coupling of district heating with the electricity system: profitability and operations (SeCoHeat)
- 2023
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- District heating systems can play key roles in the energy transition. The transition to a production mix based on renewable intermittent generation will create a larger need for ancillary services including frequency-regulation services. District heating systems typically participate in the wholesale electricity market (the so-called day-ahead market) today but do not, in general, participate in ancillary service markets. Previous studies have shown that it is technically possible to participate in these markets and that district heating systems have a role to play in these markets in the future. This requires investigating how further integration of district heating systems with the electrical grids and markets will impact operation and planning of these units. In addition, while it may be beneficial on a system level for district heating systems to participate in ancillary service markets, district heating system owners and operators will only do so if there are economic incentives to do so. The SeCoHeat project has therefore explored topics related to the profitability for individual district heating systems to participate in other electricity markets than just the day-ahead market, such as ancillary service markets. Studying sector coupling between the heat and electricity systems requires a thorough understanding of both sectors. This project has contributed to this by bringing together experts from both sides which has led to fruitful knowledge exchanges. Furthermore, some deliverables from the SeCoHeat project have been especially written to provide introduction about the heat sector to experts from the electricity sector, and vice versa. This includes an overview of the electricity markets in which district heating systems can participate, the technical requirements to participate in these markets and explanations about how profitability of participating in these markets can be computed. This also includes explanations about how the flexibility on the heat side can be sourced and provided to the electricity system and what limits this flexibility. Another important contribution of this project is the development of a Python-based open model for scheduling district system units on an hourly basis to minimize heat and electricity production costs while maximising revenues from several electricity markets. This model has been used in this project to evaluate the additional profits of participating in ancillary service markets. The results show that substantial additional profits can be made by doing so, both in historical years and in scenarios for future years. This report is a guide to the separate deliverables produced within this project. It offers an overview of the goals, methods and results from the project. The interested reader is referred to detailed descriptions in the corresponding deliverables. The SeCoHeat project was funded by Göteborg Energi AB:s stiftelse för forskning och utveckling. The work has been performed by RISE with the support of reference group members from Göteborg Energi, Vattenfall, Svenska kraftnät, IVL Svenska Miljöinstitutet, Chalmers and Profu.
|
|
| 7. |
- Krogvold, Lars, et al.
(författare)
-
Detection of a low-grade enteroviral infection in the islets of Langerhans of living patients newly diagnosed with type 1 diabetes
- 2015
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 64:5, s. 1682-1687
-
Tidskriftsartikel (refereegranskat)abstract
- The Diabetes Virus Detection study (DiViD) is the first to examine fresh pancreatic tissue at the diagnosis of type 1 diabetes for the presence of viruses. Minimal pancreatic tail resection was performed 3-9 weeks after onset of type 1 diabetes in 6 adult patients (age 24-35 years). The presence of enteroviral capsid protein 1 (VP1) and the expression of class I HLA were investigated by immunohistochemistry. Enterovirus RNA was analyzed from isolated pancreatic islets and from fresh frozen whole pancreatic tissue using PCR and sequencing. Non-diabetic organ donors served as controls. VP1 was detected in the islets of all type 1 diabetes patients (2 of 9 controls). Hyperexpression of class I HLA molecules was found in the islets of all patients (1 of 9 controls). Enterovirus specific RNA sequences were detected in 4 of 6 cases (0 of 6 controls). The results were confirmed in different laboratories. Only 1.7 % of the islets contained VP1 positive cells and the amount of enterovirus RNA was low. The results provides evidence for the presence of enterovirus in pancreatic islets of type 1 diabetic patients, being consistent with the possibility that a low grade enteroviral infection in the pancreatic islets contribute to disease progression in humans.
|
|
| 8. |
- Krogvold, Lars, et al.
(författare)
-
Function of Isolated Pancreatic Islets From Patients at Onset of Type 1 Diabetes : Insulin Secretion Can Be Restored After Some Days in a Nondiabetogenic Environment In Vitro: Results From the DiViD Study
- 2015
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 64:7, s. 2506-2512
-
Tidskriftsartikel (refereegranskat)abstract
- The understanding of the etiology of type 1 diabetes (T1D) remains limited. One objective of the Diabetes Virus Detection (DiViD) study was to collect pancreatic tissue from living subjects shortly after the diagnosis of T1D. Here we report the insulin secretion ability by in vitro glucose perifusion and explore the expression of insulin pathway genes in isolated islets of Langerhans from these patients. Whole-genome RNA sequencing was performed on islets from six DiViD study patients and two organ donors who died at the onset of T1D, and the findings were compared with those from three nondiabetic organ donors. All human transcripts involved in the insulin pathway were present in the islets at the onset of T1D. Glucose-induced insulin secretion was present in some patients at the onset of T1D, and a perfectly normalized biphasic insulin release was obtained after some days in a nondiabetogenic environment in vitro. This indicates that the potential for endogenous insulin production is good, which could be taken advantage of if the disease process was reversed at diagnosis.
|
|
| 9. |
- Krogvold, Lars, et al.
(författare)
-
Insulitis and characterisation of infiltrating T cells in surgical pancreatic tail resections from patients at onset of type 1 diabetes
- 2016
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:3, s. 492-501
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesisIt is thought that T cells play a major role in the immune-mediated destruction of beta cells in type 1 diabetes, causing inflammation of the islets of Langerhans (insulitis). The significance of insulitis at the onset of type 1 diabetes is debated, and the role of the T cells poorly understood.MethodsIn the Diabetes Virus Detection (DiViD) study, pancreatic tissue from six living patients with recent-onset type 1 diabetes was collected. The insulitis was characterised quantitatively by counting CD3+ T cells, and qualitatively by transcriptome analysis targeting 84 T and B lymphocyte genes of laser-captured microdissected islets. The findings were compared with gene expression in T cells collected from kidney biopsies from allografts with ongoing cellular rejection. Cytokine and chemokine release from isolated islets was characterised and compared with that from islets from non-diabetic organ donors.ResultsAll six patients fulfilled the criteria for insulitis (5–58% of the insulin-containing islets in the six patients had ≥ 15 T cells/islet). Of all the islets, 36% contained insulin, with several resembling completely normal islets. The majority (61–83%) of T cells were found as peri-insulitis rather than within the islet parenchyma. The expression pattern of T cell genes was found to be markedly different in islets compared with the rejected kidneys. The islet-infiltrating T cells showed only background levels of cytokine/chemokine release in vitro.Conclusions/interpretationInsulitis and a significant reserve reservoir for insulin production were present in all six cases of recent-onset type 1 diabetes. Furthermore, the expression patterns and levels of cytokines argue for a different role of the T cells in type 1 diabetes when compared with allograft rejection.
|
|
| 10. |
- Kuric, Enida, et al.
(författare)
-
Demonstration of Tissue Resident Memory CD8 T Cells in Insulitic Lesions in Adult Patients with Recent-Onset Type 1 Diabetes
- 2017
-
Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 187:3, s. 581-588
-
Tidskriftsartikel (refereegranskat)abstract
- Subtypes of CD8(+) T cells in insulitic lesions in biopsy specimens from six subjects with recent-onset type 1 diabetes (T1D) and six nondiabetic matched controls were analyzed using simultaneous multicolor immunofluorescence. Also, insulitic islets based on accumulation of CD3(+) T cells were microdissected with laser-capture microscopy, and gene transcripts associated with inflammation and autoimmunity were analyzed. We found a substantial proportion, 43%, of the CD8(+) T cells in the insulitic lesions to display a tissue resident memory T cell (TRM) (CD8(+)CD69(+)CD103(+)) phenotype in T1D subjects. Most TRM cells were located in the insulitic lesion in the endocrine-exocrine interface. TRM cells were also sporadically found in islets of control subjects. Moreover, gene expression analysis showed a lack of active transcription of genes associated with acute inflammatory or cytotoxic T-cell responses. We present evidence that a substantial proportion of T cells in insulitic lesions of recent-onset T1D patients are TRM cells and not classic cytotoxic CD8(+) T cells. Our findings highlight the need for further analysis of the T cells involved in insulitis to elucidate their role in the etiology of T1D.
|
|
