| 1. |
- Wu, Q., et al.
(författare)
-
Freight train air brake models
- 2021
-
Ingår i: International Journal of Rail transportation. - : Informa UK Limited. - 2324-8378 .- 2324-8386.
-
Tidskriftsartikel (refereegranskat)abstract
- This paper is an outcome of an international collaborative research initiative. Researchers from 24 institutions across 12 countries were invited to discuss the state-of-the-art in railway train air brake modelling with an emphasis on freight rains. Discussed models are classified as empirical, fluid dynamics and fluid-empirical dynamics models. Empirical models are widely used, and advanced versions have been used for train dynamics simulations. Fluid dynamics models are better models to study brake system behaviour but are more complex and slower in computation. Fluid-empirical dynamics models combine fluid dynamics brake pipe models and empirical brake valve models. They are a balance of model fidelity and computational speeds. Depending on research objectives, detailed models of brake rigging, friction blocks and wheel-rail adhesion are also available. To spark new ideas and more research in this field, the challenges and research gaps in air brake modelling are discussed.
|
|
| 2. |
- Amare, Azmeraw T, et al.
(författare)
-
Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
-
Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
-
Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
|
|
| 3. |
- Amare, Azmeraw, et al.
(författare)
-
Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.
- 2023
-
Ingår i: Research square. - : Research Square Platform LLC.
-
Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.
|
|
| 4. |
- Facio, Jorge I., et al.
(författare)
-
Engineering a pure Dirac regime in ZrTe5
- 2023
-
Ingår i: SciPost Physics. - : Stichting SciPost. - 2542-4653. ; 14:4
-
Tidskriftsartikel (refereegranskat)abstract
- Real-world topological semimetals typically exhibit Dirac and Weyl nodes that coexist with trivial Fermi pockets. This tends to mask the physics of the relativistic quasiparti-cles. Using the example of ZrTe5, we show that strain provides a powerful tool for in-situ tuning of the band structure such that all trivial pockets are pushed far away from the Fermi energy, but only for a certain range of Van der Waals gaps. Our results naturally reconcile contradicting reports on the presence or absence of additional pockets in ZrTe5, and provide a clear map of where to find a pure three-dimensional Dirac semimetallic phase in the structural parameter space of the material.
|
|
| 5. |
- Flex, Elisabetta, et al.
(författare)
-
Activating mutations in RRAS underlie a phenotype within the RASopathy spectrum and contribute to leukaemogenesis
- 2014
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:16, s. 4315-4327
-
Tidskriftsartikel (refereegranskat)abstract
- RASopathies, a family of disorders characterized by cardiac defects, defective growth, facial dysmorphism, variable cognitive deficits and predisposition to certain malignancies, are caused by constitutional dysregulation of RAS signalling predominantly through the RAF/MEK/ERK (MAPK) cascade. We report on two germline mutations (p.Gly39dup and p.Val55Met) in RRAS, a gene encoding a small monomeric GTPase controlling cell adhesion, spreading and migration, underlying a rare (2 subjects among 504 individuals analysed) and variable phenotype with features partially overlapping Noonan syndrome, the most common RASopathy. We also identified somatic RRAS mutations (p.Gly39dup and p.Gln87Leu) in 2 of 110 cases of non-syndromic juvenile myelomonocytic leukaemia, a childhood myeloproliferative/myelodysplastic disease caused by upregulated RAS signalling, defining an atypical form of this haematological disorder rapidly progressing to acute myeloid leukaemia. Two of the three identified mutations affected known oncogenic hotspots of RAS genes and conferred variably enhanced RRAS function and stimulus-dependent MAPK activation. Expression of an RRAS mutant homolog in Caenorhabditis elegans enhanced RAS signalling and engendered protruding vulva, a phenotype previously linked to the RASopathy-causing SHOC2(S2G) mutant. Overall, these findings provide evidence of a functional link between RRAS and MAPK signalling and reveal an unpredicted role of enhanced RRAS function in human disease.
|
|
| 6. |
- Ion, John C., et al.
(författare)
-
A comparison of gas tungsten arc and CO2 laser beam welding of AA2024
- 2001
-
Ingår i: Journal of laser applications. - : Laser Institute of America. - 1042-346X .- 1938-1387. ; 13:2, s. 79-83
-
Tidskriftsartikel (refereegranskat)abstract
- Mechanical fastening methods are used extensively to join aluminum alloys, particularly in the aerospace industries. Laser welding provides the possibility of a high productivity single-step process, with the added benefit of potential weight savings of about 10% in comparison with riveting. However, the weldability of many aluminum aerospace alloys is generally considered to be low, and little data are currently available. A procedure for CO2 laser welding of the alloy AA2024 is developed, with the use of 2319 filler wire. Weld property data are shown to achieve the requirements for the most stringent quality level of the current European workmanship standard for laser-welded joints in aluminum. Hardness and tensile strength properties are shown to be similar to those of gas tungsten arc (GTA) welds. The fatigue strength of GTA welds is superior to that of laser welds in the as-welded condition, but when the weld bead is machined flush with the plate surface the difference is reduced. The laser welds achieved the requirements of recommendations produced by the International Institute of Welding for single-sided welding of aluminum alloys. The quality of the weld toe is shown to have the greatest effect on fatigue strength.
|
|
| 7. |
- Ion, John C., et al.
(författare)
-
A second report on diagrams of microstructure and hardness for heat-affected zones in welds
- 1984
-
Ingår i: Acta Metallurgica. - : Elsevier BV. - 0001-6160. ; 32:11, s. 1949-1962
-
Tidskriftsartikel (refereegranskat)abstract
- The paper improves and extends kinetic models to include: precipitate coarsening; the use of semi-empirical equations including carbon-equivalence to predict microstructure and hardness; a comparison between the theory and data obtained from different types of real welds; and an alternative, more easily used diagram.
|
|
| 8. |
- Ion, John C., et al.
(författare)
-
Computer modelling of weld-implant testing
- 1985
-
Ingår i: Materials Science and Technology. - 0267-0836 .- 1743-2847. ; 1:5, s. 405-411
-
Tidskriftsartikel (refereegranskat)abstract
- A theoretical model is developed for determining the optimum notch position in an implant test used for predicting the susceptibility to hydrogen cracking during welding. Using a microcomputer for processing the equations for weld-bead geometry and heat flow during welding, a microstructural cross-section, with the notch positioned at the center of the grain-growth zone, and an implant testing diagram, showing the notch position and microstructure as a function of welding parameters, can be generated. A single bead-on-plate weld is used to determine the unknown kinetic and geometrical constants in the equations. It is shown that notch position is very sensitive to the type of welding process employed and that implant diagrams thus can be used to position the notch with greater reliability and hence reduce the scatter in the fracture loads measured in this test.
|
|
| 9. |
- Ion, John, et al.
(författare)
-
Laser surface modification of a 13.5% Cr, 0.6% C steel
- 1991
-
Ingår i: Journal of Materials Science. - 0022-2461 .- 1573-4803. ; 26:1, s. 43-48
-
Tidskriftsartikel (refereegranskat)abstract
- A 13.5% Cr, 0.6% C steel, with an initial microstructure of chromium carbides in a ferrite matrix, was heat-treated by scanning a high-power laser beam over the surface. The aim was to compare the physical and chemical properties produced by this type of selective surface treatment with those resulting from a conventional furnace desensitization and quench-hardening heat treatment. Surface heating homogenized the carbon originally bound in the carbides sufficiently to produce martensite, giving hardening to levels comparable with a conventional heat treatment. Chromium-rich zones, carbides and retained austenite were also detected in the heated microstructure. Surface melting produced complete homogenization of both carbon and chromium, which resulted in the retention of large amounts of austenite in the microstructure on cooling to room temperature. Subsequent refrigeration at - 196 °C transformed some of the austenite to martensite. Pitting corrosion and local reductions in hardness were observed adjacent to treated areas under certain conditions, due to precipitation of secondary carbides and elevated tempering, respectively.
|
|
| 10. |
- Kalman, Janos L, et al.
(författare)
-
Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
-
Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
-
Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
|
|
