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- Almqvist, Joachim E, 1980, et al.
(author)
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Modeling the Effect of Kv1.5 Block on the Canine Action Potential
- 2010
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In: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 99:9, s. 2726-2736
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Journal article (peer-reviewed)abstract
- A wide range of ion channels have been considered as potential targets for pharmacological treatment of atrial fibrillation. The Kv1.5 channel, carrying the IKur current, has received special attention because it contributes to repolarization in the atria but is absent or weakly expressed in ventricular tissue. The dog serves as an important animal model for electrophysiological studies of the heart and mathematical models of the canine atrial action potential (CAAP) have been developed to study the interplay between ionic currents. To enable more-realistic studies on the effects of Kv1.5 blockers on the CAAP in silico, two continuous-time Markov models of the guarded receptor type were formulated for Kv1.5 and subsequently inserted into the Ramirez-Nattel-Courtemanche model of the CAAP. The main findings were: 1), time- and state-dependent Markov models of open-channel Kv1.5 block gave significantly different results compared to a time- and state-independent model with a downscaled conductance; 2), the outcome of Kv1.5 block on the macroscopic system variable APD90 was dependent on the precise mechanism of block; and 3), open-channel block produced a reverse use-dependent prolongation of APD90. This study suggests that more-complex ion-channel models are a prerequisite for quantitative modeling of drug effects.
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- Brandt, Adam, 1993, et al.
(author)
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Quantitative High Speed Stability Assessment of a Sports Utility Vehicle and Classification of Wind Gust Profiles
- 2020
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In: SAE Technical Papers. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191 .- 2688-3627. ; 2020-April:April
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Journal article (peer-reviewed)abstract
- The automotive trends of vehicles with lower aerodynamic drag and more powerful drivetrains have caused increasing concern regarding stability issues at high speeds, since more streamlined bodies show greater sensitivity to crosswinds. This is especially pronounced for high vehicles, such as sports utility vehicles. Besides, the competitiveness in the automotive industry requires faster development times and, thus, a need to evaluate the high speed stability performance in an early design phase, preferable using simulation tools. The usefulness of these simulation tools partly relies on realistic boundary conditions for the wind and quantitative measures for assessing stability without the subjective evaluation of experienced drivers. This study employs an on-road experimental measurements setup to define relevant wind conditions and to find an objective methodology to evaluate high speed stability. The paper focuses on the events in proximity to the drivers’ subjective triggers of instability. Wind direction and magnitude, vehicle motion response, along with the subjective event triggering were measured at different conditions of the natural wind. A statistical approach was utilized to analyze the correlation between the vehicle response and subjective triggers together with the wind conditions. A correlation was established between the subjective triggers and a rapid change in lateral acceleration and yaw velocity response. The paper also proposes a set of four crosswind gust profiles of interest for driving stability, combining results from previous research and the experimental data of the natural wind obtained in this study. These findings can be used as objective measures for virtually assessing stability performance and as realistic boundary conditions for simulating wind gusts.
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| 7. |
- Jacobson, Bengt J H, 1962, et al.
(author)
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Compendium in Vehicle Motion Engineering
- 2021
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Reports (other academic/artistic)abstract
- This compendium is written for the course “MMF062 Vehicle Motion Engineering” at Chalmers University of Technology. The compendium covers more than included in that course; both in terms of subsystem designs and in terms of some teasers for more advanced studies of vehicle dynamics. Therefore, it is also useful for the more advanced course “TME102 Vehicle Modelling and Control”. The overall objective of the compendium is to educate vehicle dynamists, i.e., engineers that understand and can contribute to development of good motion and energy functionality of vehicles. The compendium focuses on road vehicles, primarily passenger cars and commercial vehicles. Smaller road vehicles, such as bicycles and single-person cars, are only very briefly addressed. It should be mentioned that there exist a lot of ground-vehicle types not covered at all, such as: off-road/construction vehicles, tracked vehicles, horse wagons, hovercrafts, or railway vehicles. Functions are needed for requirement setting, design and verification. The overall order within the compendium is that models/methods/tools needed to understand each function are placed before the functions. Chapters 3-5 describes (complete vehicle) “functions”, organised after vehicle motion directions: · Chapter 3: Longitudinal dynamics · Chapter 4: Lateral dynamics · Chapter 5: Vertical dynamics Chapter 1 introduces automotive industry and the overall way of working there and defines required pre-knowledge from “product-generic” engineering, e.g. modelling of dynamic systems. Chapter 2 also describes the subsystems relevant for vehicle dynamics: • Wheels and Tyre • Suspension • Propulsion • Braking System • Steering System • Environment Sensing System
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| 8. |
- Stigmar, Kjerstin, et al.
(author)
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Sick leave in Sweden before and after total joint replacement in hip and knee osteoarthritis patients
- 2017
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 88:2, s. 152-157
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Journal article (peer-reviewed)abstract
- Background and purpose - Little is know about patterns of sick leave in connection with total hip and knee joint replacement (THR and TKR) in patients with osteoarthritis (OA). Patients and methods - Using registers from southern Sweden, we identified hip and knee OA patients aged 40-59 years who had a THR or TKR in the period 2004-2012. Patients who died or started on disability pension were excluded. We included 1,307 patients with THR (46% women) and 996 patients with TKR (56% women). For the period 1 year before until 2 years after the surgery, we linked individual-level data on sick leave from the Swedish Social Insurance Agency. We created a matched reference cohort from the general population by age, birth year, and area of residence (THR: n = 4,604; TKR: n = 3,425). The mean number of days on sick leave and the proportion (%) on sick leave 12 and 24 months before and after surgery were calculated. Results - The month after surgery, about 90% of patients in both cohorts were on sick leave. At the two-year follow-up, sick leave was lower for both cohorts than 1 year before surgery, except for men with THR, but about 9% of the THR patients and 12-17% of the TKR patients were still sick-listed. In the matched reference cohorts, sick leave was constant at around 4-7% during the entire study period. Interpretation - A long period of sick leave is common after total joint replacement, especially after TKR. There is a need for better knowledge on how workplace adjustments and rehabilitation can facilitate the return to work and can postpone surgery.
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- Wallman, Mikael, 1979, et al.
(author)
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Assessment of cardiotoxic effects from ion channel assay data
- 2017
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In: Proceedings of Advances in Cell Based Screening 2017.
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Conference paper (other academic/artistic)abstract
- Drug-induced cardiotoxicity or torsades de pointes (TdP), a potentially lethal cardiac ventricular arrhythmia, is an adverse effect that has long been a leading cause of attrition during drug development.Minimizing the risk of this cardiotoxic effect is thus an important task during the drug development process and regulatory guidelines require new drugs to be evaluated for pro-arrhytmic risk before entering clinical testing. At present, block of the cardiac potassium channel hERG and human QT intervals are assessed as part of the current safety guidelines. Although a block of the cardiac potassium channel hERG and subsequent prolongation of the cardiac QT interval are common features of cardiotoxic drugs, there is no simple one-to-one correlation. TdP involves changes in cardiac cell repolarisation, which is dependent on the concerted activity of several ion channels including hERG, Na-, and Ca-channels. Too much emphasis on hERG as a marker has most likely hampered the development of new drugs by premature discontinuation from development.We aim to directly assess the primary clinical endpoint, namely ventricular proarrhythmia (i.e., cardiotoxicity). To achieve this, we use a data driven approach based on published data to train a neural network architecture.The technology is made easily accessible to potential users via a web based demonstrator.
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