| 11. |
- Ali, Mina, et al.
(författare)
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The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 1649-
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Tidskriftsartikel (refereegranskat)abstract
- Recently, we identified ELL2 as a susceptibility gene for multiple myeloma (MM). To understand its mechanism of action, we performed expression quantitative trait locus analysis in CD138+ plasma cells from 1630 MM patients from four populations. We show that the MM risk allele lowers ELL2 expression in these cells (Pcombined = 2.5 × 10−27; βcombined = −0.24 SD), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause–effect relationship. Our results provide mechanistic insight into MM predisposition.
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| 12. |
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| 13. |
- Dewan, Ramita, et al.
(författare)
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Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.
- 2021
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Ingår i: Neuron. - : Elsevier BV. - 1097-4199 .- 0896-6273. ; 109:3, s. 448-460.e4
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Tidskriftsartikel (refereegranskat)abstract
- We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered.
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| 14. |
- Elingaard-Larsen, Line O., et al.
(författare)
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Circulating Metabolomic and Lipidomic Signatures Identify a Type 2 Diabetes Risk Profile in Low-Birth-Weight Men with Non-Alcoholic Fatty Liver Disease
- 2023
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which increased liver fat content influences differences in circulating metabolites and/or lipids between low-birth-weight (LBW) individuals, at increased risk of type 2 diabetes (T2D), and normal-birth-weight (NBW) controls is unknown. The objective of the study was to perform untargeted serum metabolomics and lipidomics analyses in 26 healthy, non-obese early-middle-aged LBW men, including five men with screen-detected and previously unrecognized non-alcoholic fatty liver disease (NAFLD), compared with 22 age- and BMI-matched NBW men (controls). While four metabolites (out of 65) and fifteen lipids (out of 279) differentiated the 26 LBW men from the 22 NBW controls (p ≤ 0.05), subgroup analyses of the LBW men with and without NAFLD revealed more pronounced differences, with 11 metabolites and 56 lipids differentiating (p ≤ 0.05) the groups. The differences in the LBW men with NAFLD included increased levels of ornithine and tyrosine (PFDR ≤ 0.1), as well as of triglycerides and phosphatidylcholines with shorter carbon-chain lengths and fewer double bonds. Pathway and network analyses demonstrated downregulation of transfer RNA (tRNA) charging, altered urea cycling, insulin resistance, and an increased risk of T2D in the LBW men with NAFLD. Our findings highlight the importance of increased liver fat in the pathogenesis of T2D in LBW individuals.
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| 15. |
- Elmroth, Erik, 1964-, et al.
(författare)
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Self-management challenges for multi-cloud architectures
- 2011
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Ingår i: Towards a Service-Based Internet. - Berlin, Heidelberg : Springer Berlin/Heidelberg. - 9783642247545 - 9783642247552 ; , s. 38-49
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Konferensbidrag (refereegranskat)abstract
- Addressing the management challenges for a multitude of distributed cloud architectures, we focus on the three complementary cloud management problems of predictive elasticity, admission control, and placement (or scheduling) of virtual machines. As these problems are intrinsically intertwined we also propose an approach to optimize the overall system behavior by policy-tuning for the tools handling each of them. Moreover, in order to facilitate the execution of some of the management decisions, we also propose new algorithms for live migration of virtual machines with very high workload and/or over low-bandwidth networks, using techniques such as caching, compression, and prioritization of memory pages.
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| 16. |
- Frigyesi, Ildiko, et al.
(författare)
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Robust isolation of malignant plasma cells in multiple myeloma.
- 2014
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 123:9, s. 1336-1340
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Tidskriftsartikel (refereegranskat)abstract
- Molecular characterization of malignant plasma cells is increasingly important for diagnostic and therapeutic stratification in multiple myeloma (MM). However, the malignant plasma cells represent a relatively small subset of bone marrow cells, and need to be enriched prior to analysis. Currently, the cell surface marker CD138 (SDC1) is used for this enrichment, but has an important limitation in that its expression decreases rapidly after sampling. Seeking alternatives to CD138, we performed a computational screen for myeloma plasma cell markers and evaluated seven candidates systematically. Our results conclusively show that the markers CD319 (SLAMF7/CS1) and CD269 (TNFRSF17/BCMA) are considerably more robust than CD138, and enable isolation of myeloma plasma cells under more diverse conditions, including in samples that have been delayed or frozen. Our results form the basis of improved procedures for characterizing cases of multiple myeloma in clinical practice.
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| 17. |
- Ghanbarikarekani, Mina, et al.
(författare)
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Minimizing the stop time of private vehicles at intersections with LRT signal priority systems
- 2020
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Ingår i: Transportation Research Procedia. - : Elsevier BV. - 2352-1465 .- 2352-1457. ; 48:2020, s. 939-945
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Konferensbidrag (refereegranskat)abstract
- There are some strategies suggested to improve the performance of intersections and increase the demand for public vehicles by prioritizing them. To this end, several methods have been used such as Transit Signal Priority (TSP) system for Light Rail transit (LRT). LRT signal priority is a timing strategy that gives priority to LRTs at signalized intersections through changing the sequence of phases, extending green time and reducing red time at LRT's phase. In this paper, we propose a model to improve LRT signal priority systems. The developed model minimizes the green extension and red reduction of LRT's phase by estimating an optimal speed for LRTs reaching the stop line. Consequently, the priority of LRTs would be maintained while the performance of private vehicles would be improved by decreasing their stop time.
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| 18. |
- Hertzman, S., et al.
(författare)
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Nitrogen Solubility in Alloy Systems Relevant to Stainless Steels
- 2021
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Ingår i: Metallurgical and Materials Transactions. A. - : Springer Nature. - 1073-5623 .- 1543-1940. ; 52:9, s. 3811-3820
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Tidskriftsartikel (refereegranskat)abstract
- High-performance stainless steels are alloyed with nitrogen for several different reasons. For the austenitic grades, the kinetics of deleterious phase transformations are delayed, the strength is increased, and the corrosion resistance is improved. For duplex steels, the weldability and corrosion resistance depend directly on their nitrogen contents. Reliable databases are crucial for the development of new stainless steels and their processing. In order to calibrate the existing thermodynamic data, a series of experiments was undertaken. Several laboratory alloys in Fe–Cr–X systems, where X = Ni, Mn, Cu, were reacted with nitrogen gas at nitrogen activities 0.5 and 1 in the temperature range from 1050 °C to 1350 °C and subsequently analyzed for nitrogen solubility and phase constitution. A novel, simplified experimental technique was used, providing a dew point that is low enough to allow for fast nitrogen transport through the specimen surface, ensuring equilibrium conditions. The results are compared to thermodynamic equilibrium calculations.
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| 19. |
- Imani, Ali, et al.
(författare)
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Key Indicators Affecting Hospital Efficiency : A Systematic Review
- 2022
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Ingår i: Frontiers In Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 10
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Forskningsöversikt (refereegranskat)abstract
- Background: Measuring hospital efficiency is a systematic process to optimizing performance and resource allocation. The current review study has investigated the key input, process, and output indicators that are commonly used in measuring the technical efficiency of the hospital to promote the accuracy of the results. Methods: To conduct this systematic review, the electronic resources and databases MEDLINE (via PubMed), Scopus, Ovid, Proquest, Google Scholar, and reference lists of the selected articles were used for searching articles between 2010 and 2019. After in-depth reviews based on the inclusion and exclusion criteria, among 1,537 studies, 144 articles were selected for the final assessment. Critical Appraisal Skills Programme (CASP) Checklist was used for evaluating the quality of the articles. The main findings of studies have been extracted using content analysis. Results: After the final analysis, the Context/Input indicators that were commonly considered by studies in analyzing hospital technical efficiency include different variables related to Hospital Capacity, Structure, Characteristics, Market concentration, and Costs. The Process/Throughput indicators include different variables related to Hospital Activity or services-oriented process Indicators, Hospital Quality-oriented process indicators, and Hospital Educational processes. Finally, the Output/Outcome indicators include different variables related to Hospital Activity-related output variables and Quality-related output/outcomes variables. Conclusion: This study has identified that it is necessary to mix and assess a set of input, process, and output indicators of the hospital with both quantitative and qualitative indicators for measuring the technical efficiency of hospitals comprehensively.
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| 20. |
- Jonsson, Stefan, et al.
(författare)
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Identification of sequence variants influencing immunoglobulin levels
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49:8, s. 1182-1191
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulins are the effector molecules of the adaptive humoral immune system. In a genome-wide association study of 19,219 individuals, we found 38 new variants and replicated 5 known variants associating with IgA, IgG or IgM levels or with composite immunoglobulin traits, accounted for by 32 loci. Variants at these loci also affect the risk of autoimmune diseases and blood malignancies and influence blood cell development. Notable associations include a rare variant at RUNX3 decreasing IgA levels by shifting isoform proportions (rs188468174[C>T]: P = 8.3 × 10(-55), β = -0.90 s.d.), a rare in-frame deletion in FCGR2B abolishing IgG binding to the encoded receptor (p.Asn106del: P = 4.2 × 10(-8), β = 1.03 s.d.), four IGH locus variants influencing class switching, and ten new associations with the HLA region. Our results provide new insight into the regulation of humoral immunity.
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