Publikationer från Uppsala Universitet
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High-strain-rate fracture behavior of rock-like materials : Insights from Split Hopkinson Pressure Bar testing and dynamic phase-field modeling
No full textThis study integrates a hydrostatic–spectral–deviatoric decomposition within a dynamic phase-field finite element framework to assess its effectiveness in simulating fracture patterns in brittle materials subjected to high strain-rate compressive loading. The investigation focuses on Split Hopkinson Pressure Bar (SHPB) experiments using gypsum plaster specimens with central holes, tested in a synchronously assembled setup. The hydrostatic–spectral–deviatoric decomposition enables a distinction between tensile and compressive strain energy components to accurately model dynamic fracture processes in quasi-brittle materials under compressive and mixed-mode loading, where traditional formulations often fall short. To maintain consistency, the numerical simulations were calibrated using material parameters previously identified through quasi-static tests on the same material and different geometries. The simulated results closely mirrored experimental observations, successfully reproducing key features such as crack paths, propagation sequence, timing, boundary motion, and crack tip velocity. This enhanced modeling approach offers valuable insight into dynamic fracture behavior in brittle systems and underscores its potential for improving predictive capabilities under high strain-rate loading scenarios
PMEL governs autosomal dominant inheritance of white-tail independent of yellow body plumage in chickens (Gallus gallus domesticus)
No full textRegion-specific feather pigmentation is widespread in birds, yet the genetic mechanisms enabling independent control of body and tail plumage remain poorly understood. The white-tailed (WT) phenotype in Wuhua yellow chickens, which exhibit yellow body plumage but pure white tail feathers, provides an ideal model for dissecting such modular genetic regulation. Genetic analysis of F1 and F2 populations (n = 137) derived from a cross with Huaixiang (black-tailed, BT) chickens revealed an autosomal dominant inheritance pattern for the WT trait, with a 3:1 segregation ratio (105 WT: 32 BT; chi 2 = 0.20, P = 0.66) in the F2 generation-independent of the yellow body plumage locus. Integrating genome-wide association study of 47 F2 roosters with population resequencing (n = 50), we identified a highly significant locus on chromosome 33 (P = 1.35E-8) harboring PMEL as the sole credible candidate. Tail follicle transcriptome profiling (4 WT vs. 4 BT) uncovered 1,712 differentially expressed genes, with coordinated downregulation of the entire melanogenesis pathway (normalized enrichment score = -1.914, FDR = 0.003). PMEL ranked among the most strongly suppressed genes (log2FC = -2.18, FDR = 5.58E-06). Furthermore, genome-wide alternative splicing analysis identified 2,764 significant events among 30,473 detected, indicating widespread post-transcriptional regulation. Consistent with this global pattern, the PMEL locus exhibited markedly reduced splicing complexity in WT chickens, characterized by a systematic shift toward simpler isoforms. Thus, four orthogonal lines of evidence-genomic association, transcriptional repression, pathway-level melanogenesis shutdown, and splicing simplification-converge on PMEL as the causal gene underlying this autosomal dominant, tail-specific depigmentation. Our findings establish PMEL as the primary regulator underlying this autosomal dominant trait, paving the way for understanding modular avian coloration and enabling its application in precision breeding programs
AI Data Governance : Overlaps Between the AI Act and the GDPR
No full textThis article examines the overlaps between the AI Act and the GDPR, analysing their overall relationship, conceptual similarities and differences, as well as specific provisions in the AI Act that explicitly overlap with the GDPR. The primary focus of this article lies on AI data governance, with a detailed analysis of the requirements set out in Article 10 AI Act. This provision establishes quality criteria for data and data governance in high-risk AI systems that rely on training AI models with data. The article introduces a novel approach to understanding, interpreting, and applying these criteria to facilitate GDPR compliance. As a result, we propose a principles-based framework for AI data governance, categorising the quality criteria in Article 10 into three overarching principles: data accuracy, data transparency, and data fairness. To ensure practical quality assurance, providers of high-risk AI systems should adopt specific methods outlined in the AI Act, such as data-preparation processing operations and the processing of personal data for bias detection and correction. Finally, we propose a cycle-approach to AI data governance, aligning the requirements of Article 10 AI Act with the limitations imposed by the GDPR
Cough plates as a non-invasive alternative for pathogen detection in paediatric community-acquired pneumonia
No full textAim: To evaluate diagnostic performance of cough plates compared to sputum samples in children with suspected pneumonia. Methods: Microbiological samples were collected after saline inhalation from 53 children. Results: Pathogens were recovered in similar rates with partial concordance. Conclusions: Cough plates may represent a promising alternative to sputum samples
Characterization of the anticancer effect of mebendazole and its interaction with standard cytotoxic drugs in patient tumor cells ex vivo and in an in vivo mouse model
No full textMebendazole (Mbz), a well‑known anthelminthic drug, has demonstrated anticancer properties in tumor models and patients, and is thus under consideration for repositioning into an anticancer drug. Mbz is directly cytotoxic in cell lines by various mechanisms and acts indirectly via immunomodulation. In the present study, the anticancer effects of Mbz, alone and in combination with cytotoxic drugs, were further characterized using primary cultures of patient tumor cells ex vivo and the murine colon cancer cell line, CT26, in vitro and in vivo. Patient‑derived tumor cells from acute myeloid leukemia (AML) and ovarian, colorectal and renal cancer were exposed to Mbz alone and, for solid tumors and the CT26 cell line, in combination with irinotecan, cisplatin or gemcitabine (patient cells only). Cytotoxicity was assessed using the fluorometric microculture cytotoxicity assay. In vivo, the antitumor effects of Mbz and irinotecan, alone and in combination, were evaluated in the BALB/c CT26 colon cancer mouse model by tumor growth measurements and flow cytometric analysis of tumor immune cell infiltration. In the patient cell samples, Mbz showed modest single‑agent cytotoxicity, with the AML samples being the most sensitive, and displayed enhanced effects when combined with cytotoxic drugs, particularly irinotecan. CT26 cells showed modest dose‑independent sensitivity to Mbz, which enhanced the effect of both cisplatin and irinotecan. In vivo, Mbz and irinotecan both inhibited tumor growth, but the combination did not significantly outperform Mbz alone. Flow cytometry of the resected mouse tumors indicated that Mbz promoted macrophage polarization from the M2 to M1 phenotype, suggesting that immune modulation may contribute to its anticancer effect. Mbz has features making it a candidate for repositioning into an anticancer drug and part of its effect may be mediated by macrophage modulation
Design of 3D spheroid models for drug-response studies of HER2-targeted radiopharmaceuticals.
No full textThe development of targeted radionuclide- and chemotherapeutics-based drugs requires in vitro models that reflect the structural and molecular complexity of solid tumors. Here, we present a high-throughput 3D cell culture platform for targeted drug response studies. The platform was based on agarose micro-dishes that generate 81 tumor spheroids. The platform was validated across eight human and murine cancer cell lines that overexpress receptors of the HER family. The high spheroid yield supports robust quantitative analysis of binding of radiolabeled compounds, while spheroid trapping in microwells enables medium exchange for precise drug exposure. Therefore, we evaluated targeted radionuclide therapy of EMT-HER2 spheroids using the HER2-specific affibody PEP48937 labelled with terbium-161. We demonstrated both HER2-specific binding to spheroids and receptor-specific therapeutic effects, including reduced spheroid proliferation over time and impaired cell migration. These results highlight the platform potential to accelerate the development of targeted cancer therapeutics for biomedicine
Christoffel transform and multiple orthogonal polynomials
No full textWe investigate multiple orthogonal polynomials associated with the system of measures obtained by applying a Christoffel transform to each of the orthogonality measures. We present an algorithm for computing the transformed recurrence coefficients and determinantal formulas for the transformed multiple orthogonal polynomials of type I and type II. We apply these results to show that zeros of multiple orthogonal polynomials of an Angelesco or an AT system interlace with the zeros of the polynomials corresponding to its onestep Christoffel transform. This allows us to prove a number of interlacing properties satisfied by the multiple orthogonality analogues of classical orthogonal polynomials. For the discrete polynomials, this also produces an estimate on the smallest distance between consecutive zeros. We also identify a connection between the Christoffel transform of orthogonal polynomials and multiple orthogonality systems containing a finitely supported measure. In consequence, the compatibility relations for the nearest neighbour recurrence coefficients provide a new algorithm for the computation of the Jacobi coefficients of the one-step or multi-step Christoffel transforms
Boundedness of weak solutions to degenerate Kolmogorov equations of hypoelliptic type in bounded domains
No full textWe establish the boundedness of weak subsolutions for a class of degenerate Kolmogorov equations of the hypoelliptic type, compatible with a homogeneous Lie group structure, within bounded product domains using the De Giorgi iteration. We employ the renormalization formula to handle boundary values and provide energy estimates. An – type embedding estimate derived from the fundamental solution is utilized to incorporate lower-order divergence terms. This work naturally extends the boundedness theory for uniformly parabolic equations, with matching exponents for the coefficients
Structural determination of self-assembled aggregates formed by a therapeutic cyclical peptide and an ionic surfactant in aqueous solution
No full textAmphiphilic compounds, such as phospholipids or surface-active substances, are present in biological systems and can be part of pharmaceutical formulations. As a consequence, all pharmaceutically active ingredients will encounter amphiphilic compounds, either in the formulation or after administration. With the growing interest in peptide-based pharmaceuticals, there is a need to enhance the understanding of the interactions between peptides and amphiphilic compounds. In this particular study, we have chosen to study mixtures of the comparatively small cyclical octapeptide lanreotide and the conventional anionic surfactant sodium dodecylsulfate (SDS). This was done by examining the self-assembly structures formed in lanreotide-SDS mixtures using light scattering and small-angle X-ray scattering (SAXS). Above the critical micelle concentration (cmc) of SDS, the large excess of SDS could solubilize all lanreotide and form small micelles with lanreotide attached to the interface. Upon dilution to concentrations below the cmc of SDS, a suspension with dispersed solid nanoparticles is formed. The solid nanoparticles grow in size with decreasing concentration and, eventually, precipitate. The precipitated material is arranged in a liquid crystalline micellar phase, consisting of small close-packed SDS micelles with peptide adsorbed at the interface. We were able to conclude that lanreotide does not form mixed micelles with SDS, indicating that it lacks the amphiphilic properties required to integrate fully with SDS behaving as a cosurfactant. In contrast, lanreotide attaches to the interface of SDS micelles, resembling the interactions of polymers, proteins, and nucleic acids with surfactants
Svenska villkorskonstruktioner och axiologi
No full textThree types of previously unstudied axiological conditional constructions are investigated. The first type is the potential construction with Quantifiers of Factual Proximity (QPF): Om du säger ett ord tillQPF slår jag dig på käften ('If you say one more word, I will punch you in the face'). The second type is the counterfactual construction with QPF: Om han tagit ett steg till, hade han varit död ('If he had taken one more step, he would have been dead'). The third type is the norm-breaking potential construction with the Compound conditional and the Pluperfect: Det skulle ha betytt allt om jag hade fått dom ('It would mean [lit. would have meant] everything if I got [lit. had got] them'). The different speech acts that the constructions perform are also studied: the construction types carry out expressive speech acts and some other speech acts as "threats" and "promises". From a typological perspective, it will be contended that the first and the second construction types are universal, while the third is language-specific