Publikationer från Uppsala Universitet
Not a member yet
127603 research outputs found
Sort by
Chemogenomic Screening in a Patient-Derived 3D Fatty Liver Disease Model Reveals the CHRM1-TRPM8 Axis as a Novel Module for Targeted Intervention
No full textMetabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of chronic liver disease with few therapeutic options. To narrow the translational gap in the development of pharmacological MASH treatments, a 3D liver model from primary human hepatocytes and non-parenchymal cells derived from patients with histologically confirmed MASH was established. The model closely mirrors disease-relevant endpoints, such as steatosis, inflammation and fibrosis, and multi-omics analyses show excellent alignment with biopsy data from 306 MASH patients and 77 controls. By combining high-content imaging with scalable biochemical assays and chemogenomic screening, multiple novel targets with anti-steatotic, anti-inflammatory, and anti-fibrotic effects are identified. Among these, activation of the muscarinic M-1 receptor (CHRM1) and inhibition of the TRPM8 cation channel result in strong anti-fibrotic effects, which are confirmed using orthogonal genetic assays. Strikingly, using biosensors based on bioluminescence resonance energy transfer, a functional interaction along a novel MASH signaling axis in which CHRM1 inhibits TRPM8 via G(q/11) and phospholipase C-mediated depletion of phosphatidylinositol 4,5-bisphosphate can be demonstrated. Combined, this study presents the first patient-derived 3D MASH model, identifies a novel signaling module with anti-fibrotic effects, and highlights the potential of organotypic culture systems for phenotype-based chemogenomic drug target identification at scale
Design of Self-excited Synchronous Motor for Electric Vehicle Applications.
No full textDue to global concern regarding increasing CO2 emissions and noise pollution in the field of mobility, there is a need of finding new sustainable solutions for the future in the Automotive Industry. There is an increasing demand for sustainable and efficient electric propulsion system which has to explore the self-excited synchronous motors (SESMs) as a feasible alternative to permanent magnet synchronous motors (PMSMs). Self-Excited eliminates the need of the external exciter sources, instead relying on an integrated excitation system which enhances reliability and performance. This report discusses the fundamental design of self-excited Wound Rotor Synchronous Motor, which includes rotor excitation, optimization techniques for high torque density, Induced voltage and current in harvesting coils, and the torque and power at different load angles at different speeds. In this Design of self-excited Wound Rotor Sychronous Motor we are harvesting the Slot harmonic power by adding harvesting coils on rotor poles.This investigation is based on simulation, which is carried out using ANSYS Maxwell in order to get accurate results regarding the machine performance. Additionally, the study discusses the impact of Self-excited WRSM on improving energy utilization. Simulation results displays the feasibility of Self-excited WRSM with respect to PMSMs in real world EV applications, which is an alternative way towards advancements in electric mobility without Rare-earth materials.
PKSmart : an open-source computational model to predict intravenous pharmacokinetics of small molecules
No full textDrug exposure, a key determinant of drug safety and efficacy, is governed by pharmacokinetic (PK) parameters such as volume of distribution (VDss), clearance (CL), half-life (t½), fraction unbound in plasma (fu), and mean residence time (MRT). In this study, we developed machine learning models to predict human PK parameters for 1,283 unique compounds using molecular structure, physicochemical properties, and predicted animal PK data. Our approach involved a two-stage modeling pipeline. First, we trained models to predict rat, dog, and monkey PK parameters (VDss, CL, fu) from chemical structure and properties for 371 compounds. These models were used to predict animal PK values for 1,283 unique compounds with human PK data. These animal PK predictions were then integrated with molecular descriptors and fingerprints to build Random Forest models for human PK parameters. The models demonstrated consistent performance across nested cross-validation and external validation sets, with predictive accuracy for VDss comparable to proprietary models developed by AstraZeneca. Notably, human VDss and CL predictions achieved external R2 values of 0.39 and 0.46, respectively. To support broad accessibility and integration into early drug discovery workflows such as Design-Make-Test-Analyze (DMTA), we developed PKSmart (https://broad.io/PKSmart), a freely available web application. All code and models are also open source, enabling local deployment. To our knowledge, this represents the first public suite of PK prediction models with performance on par with industry standard models.Scientific contributionThis study introduces the first publicly available pharmacokinetic (PK) models that match industry-standard predictions, utilizing molecular structural fingerprints, physicochemical properties, and predicted animal PK data to model human pharmacokinetics. Our approach is validated through repeated nested cross-validation and an external test set, including comparing predictions to an industry standard model. The models are released via a web-hosted application (https://broad.io/PKSmart) for wider accessibility and utility in drug development processes
Search for the jet-induced diffusion wake in the quark-gluon plasma via measurements of jet-track correlations in photon-jet events in Pb + Pb collisions at √\u88\u9asNN=5.02 TeV with the ATLAS detector
No full textThis paper presents a measurement of jet-track correlations in photon-jet events, using 1.72 nb-1 of Pb+Pb data at √sNN = 5.02 TeV recorded with the ATLAS detector at the LHC. Events with energetic photon-jet pairs are selected, where the photon and jet are approximately back-to-back in azimuth. The angular correlation between jets and charged-particle tracks with transverse momentum (pT) in the range 0.5-2.0 GeV in the hemisphere opposite to the jet, |ΔΦ(jet,track)| > π/2, is measured as a function of their relative pseudorapidity difference, |Δη(jet,track)|. In central Pb+Pb collisions, these correlations are predicted to be sensitive to the diffusion wake in the quark-gluon plasma resulting from the lost energy of high-pT partons traversing the plasma, with a characteristic modification as a function of |Δη(jet,track)|. The correlations are examined with different selections on the jet-to-photon pT ratio to select events with different degrees of energy loss. No diffusion wake signal is observed within the current sensitivity and upper limits at 95% confidence level on the diffusion wake amplitude are reported.For complete list of authors see http://dx.doi.org/10.1103/PhysRevC.111.044909</p
Utfall av icke-kirurgisk behandling med eller utan halskrage vid stabila subaxiala nackfrakturer: En nationell registerstudie
No full text
Skapa skulptur i samverkan : Elli Hembergs självrepresentation som skulptör under 1900-talets senare hälft
No full textThis study examines how the artist Elli Hemberg (1896 - 1994) represents herself as a sculptor during the latter half of the 20th century in Swedish cultural life and art world. The study´s research questions are:1) How does Elli Hemberg represent herself as a sculptor to contemporary society? 2) What is Elli Hemberg´s view on sculpture and the role of the sculptor in society? 3) How is Elli Hemberg´s self-representation as a sculptor influenced by different ideals and influences in contemporary cultural life and art climate? The theoretical framework of the study is based on cultural sociology, art history and historical theory. Thematic analysis (TA) was used as analytical method to analyze patterns of meaning within textual data, i. e. the artist´s diaries, letters and other documents, as well as a film interview. Through TA, three main themes emerged, which were analyzed and interpreted in the form of a three-part narrative under the headings: The creation of monumental sculpture requires collaborators and self-confidence, Sculpture is living architecture and Art has nothing to do with social policy. The results showed Elli Hemberg´s ambition to represent herself in a trustworthy role as a sculptor in contemporary society in a social network of supportive and loyal colleagues. Furthermore, the results showed how Hemberg represents herself through the creation of abstract sculptures with rhythm and movement inspired by the theory of dynamic symmetry and that the goal of Hemberg´s sculpture creation is to achieve unity and wholeness without representational and narrative content. The results also show that Hemberg's self-representation is influenced by the Swedish society's investments in public art, as well as the many artistic trends and movements of the 20th century and the post-war period
Den nylatinska poesin och Samuel Älf : Uppsatser om en förbisedd litteratur och en samlare i dess mitt
No full textOf Lattices and Lines : Building A Highly Efficient Wind Farm Flow Solver With The Lattice Boltzmann Method
No full textHigh-fidelity Large Eddy Simulation (LES) is the most common method for researchers to understand the highly complex interactions of wind farms and the atmospheric boundary layer (ABL), but is extremely expensive in terms of computational cost. The lattice Boltzmann method (LBM) can reduce computational cost of wind farm simulations by several orders of magnitude by efficiently leveraging graphics processing units (GPUs). This thesis develops a software framework to simulate wind farms in the ABL using an GPU-resident LBM solver that is both accurate and computationally efficient. First, theoretical and runtime requirements for such a framework are established. It is found that most of the required methodology is available and runtime requirements for many industry applications can be met with available methodology and hardware. Then, a framework consisting of the GPU-resident LBM solver VirtualFluids and the turbine modelling tool WiFI is developed. The framework is validated against benchmark measurements and other LES solvers. Furthermore, the effect of resolution on accuracy and correction methods for rotor modelling at coarse resolution are studied. Finally, the model is extended to simulate thermally stratified boundary layers. The framework exhibits excellent computational efficiency and is as accurate as other LES solvers. By enabling simulations at coarse resolutions, computational performance can be increased even further. A predecessor of the developed framework is used to demonstrate how the LBM enables novel and accelerates traditional research approaches. The ability to quickly generate large amounts of training data enables the use of data-driven methods, for example, a convolutional neural network to predict average flow quantities. Furthermore, larger parameter spaces can be examined, here, for example, of the helix approach for wind-farm flow control. This thesis matures the LBM for wind energy from academic cases towards real-world applicability, enabling industrial use of LES and demonstrating its benefits for research. Further expansion of modelling capabilities to include complex terrain and forested conditions is needed as well as more extensive validation
Evaluation of Randox Daytona+ Assay for Quantifying Creatinine in Plasma Samples
No full textTotal laboratory automation enhances efficiency, reduces costs, and improves quality by automating tasks. It minimizes errors and turnaround time but has downsides, including high initial costs, risk of undetected errors, and the need for staff retraining due to changing technological demands. As for students, their exposure to automated methods is often limited. As laboratory automation is increasing, this lack of familiarity with automation poses a challenge. This study aimed to implement more automation to the program for biomedical scientists at Technological University Dublin by evaluate the use of creatinine reagent for quantifying creatinine in plasma on the Randox Daytona+ analyser. To validate the instrument the following tests were made: accuracy, precision, linearity, limit of quantification, carryover, interference and stability. Plasma samples were collected from Mater Hospital and blood was drawn from a donor to use as a sample to pursue this study. Moreover, quality controls were used to evaluate the instrument for quantifying creatinine. The study showed relevant results for implementing the instrument to educational laboratories. Accuracy showed a standard deviation to 9,740 µmol/L with a standard variation of 9.738 µmol/L. Measurements from the precision gave accurate coefficient of variation when compared to the creatinine threshold which was 5%. From the linearity study a R-square value was calculated to 0.995. Moreover, the results from the interference study were accurate to previous studies. Therefore, the Randox Daytona+ analyser was ready to be implemented into the education of biomedical scientists at Technological University Dublin to prepare students for work