Publikationer från Uppsala Universitet
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Regulation of airway fumarate by host and pathogen promotes Staphylococcus aureus pneumonia
No full textStaphylococcus aureus is a leading cause of healthcare-associated pneumonia, contributing significantly to morbidity and mortality worldwide. As a ubiquitous colonizer of the upper respiratory tract, S. aureus must undergo substantial metabolic adaptation to achieve persistent infection in the distinctive microenvironment of the lung. We observed that fumC, which encodes the enzyme that converts fumarate to malate, is highly conserved with low mutation rates in S. aureus isolates from chronic lung infections. Fumarate, a pro-inflammatory metabolite produced by macrophages during infection, is regulated by the host fumarate hydratase (FH) to limit inflammation. Here, we demonstrate that fumarate, which accumulates in the chronically infected lung, is detrimental to S. aureus, blocking primary metabolic pathways such as glycolysis and oxidative phosphorylation (OXPHOS). This creates a metabolic bottleneck that drives staphylococcal FH (FumC) activity for airway adaptation. FumC not only degrades fumarate but also directs its utilization into critical pathways including the tricarboxylic acid (TCA) cycle, gluconeogenesis and hexosamine synthesis to maintain metabolic fitness and form a protective biofilm. Itaconate, another abundant immunometabolite in the infected airway enhances FumC activity, in synergy with fumarate. In a mouse model of pneumonia, a ΔfumC mutant displays significant attenuation compared to its parent and complemented strains, particularly in fumarate- and itaconate-replete conditions. Our findings underscore the pivotal role of immunometabolites in promoting S. aureus pulmonary adaptation
Measurement of W±-boson differential cross-sections in proton-proton collisions with low pile-up data at √\u88\u9as=5.02TeV and 13TeV with the ATLAS detector
No full textHigh precision single-differential W +/--boson production cross-sections as a function of electron or muon transverse momentum pT or their pseudorapity η, as well as double-differential cross-sections as functions of these variables, are measured in proton-proton collisions at centre-of-mass energies √ s = 5.02TeV and 13TeV. The W-boson charge asymmetry as a function of lepton. is also measured. The data, collected in dedicated runs at reduced instantaneous luminosity with the ATLAS detector at the Large Hadron Collider, correspond to integrated luminosities of 255 pb(-1) at 5.02TeV and 338 pb(-1) at 13TeV. The measurements are in agreement with Standard-Model predictions calculated at next-to-next-to-leading-order in the strong coupling constant as including transverse-momentum resummation at next-to-next-to-leading logarithmic accuracy using several parton distribution functions. The impact of the measured differential cross-sections as a function of lepton. on the determination of these functions is studied using a profiling technique.For complete list of authors see http://dx.doi.org/10.1140/epjc/s10052-025-14178-x</p
Inclusion and understanding of farmers' perspectives in policies and policymaking for greenhouse gas removal
No full textThe European Commission aims to facilitate a just transition towards climate neutrality in 2050 (no net greenhouse gas emissions) and acknowledges agriculture's potential to contribute to greenhouse gas removal (GGR). But the sector is currently struggling with economic profitability and a declining farmers' population. Farmers, moreover, often tend to be critical of sustainability and environmental policies, which negatively influences their willingness to engage with GGR. Based on insights from justice theory we assume that farmers' potential reservations towards GGR can be mitigated by ensuring that their perspectives are included and inform the design and execution of GGR policies. But to what extent do policymakers understand and consider the inclusion of farmers' perspectives on GGR? To explore this question we analyse key EU and Swedish GGR policy documents as well as interviews with policymakers against the procedural justice criteria of voice, transparency, impartiality and consistency. The analysis identifies the following challenges that influence the uptake of farmers' perspectives in GGR measures: (1) the legitimacy of farmers' perspectives are affected by the ways in which policymakers perceive the representativeness of intermediaries; (2) the timing of inclusion of different intermediaries affects meaningful inclusion of farmers' perspectives in GGR policies; and finally (3) intermediaries and other stakeholders have different experience and capacities for navigating the complex and opaque body of policies, policymaking processes and competing interests (together referred to as a policy maze). Based on these results we conclude that meeting these three challenges can help to overcome farmers' scepticism against environmental policy and, as such, strengthen the effectiveness of GGR measures
Estimating PSA Growth Rates After Prostate Cancer Treatment
No full textThis essay studied methods for estimating the rate of growth of prostate-specificantigen (PSA) levels in the blood following prostate cancer treatment, particularlyin cases where only limited data are available. Monitoring the rate of PSA increaseis clinically important, as it can indicate cancer recurrence or progression and ahigh growth rate is associated with higher risk of death from prostate cancer. Thegrowth rate after surgery is particularly problematic to estimate since PSA valuesare typically below the detection limit (0.1 ng/ml) for a short or long period. To estimate the growth rate of PSA at the time when it has become measurable(two consecutive values above 0.1 ng/ml), we aimed to test and compare differentestimation techniques by simulating a dataset that imitated PSA behavior overtime in patients. The estimation methods evaluated included maximum likelihoodestimation (MLE), complete case analysis (CCA) with lookback and deterministicimputation (DI). A simulation study was conducted on the generated dataset toassess how accurately each method could estimate the growth rate under varyingchoices of parameters. These results were then compared to analyses on a real-lifedataset. In the simulated datasets, MLE performed the best in estimating the PSA growthrate, followed by CCA using all available information. DI showed somewhat loweraccuracy but still performed reasonably well, whereas CCA with limited informationgenerally produced the least accurate estimates. In the real-world dataset, the relativeperformance of the methods differed from the theoretical results; it was unclearwhich method performed best. These findings suggest that while MLE is generally the most effective for estimatingthe rate of growth of PSA, simpler methods like DI may be preferable when thenumber of available measurements is very limited
Infinite series and products
No full textDetermining wether or not a series converges or not always trivial, therefore itis useful to have convergence tests that can be applied in different situations todetermine convergence. This thesis will mainly encompass some properties of series,convergence tests with applications, and and a little about convergence of productsand how they relate to series. The main result of the thesis being a classification ofwhich real values a specified hypergeometric series converges for, using Gauss’s test
Advancing transdisciplinary research on Madagascar's grassy biomes to support resilience in ecosystems and livelihoods
No full textGrassy biomes (savanna and grasslands) are globally extensive and host a unique biodiversity that is of central importance to human livelihoods. We focus here on the island of Madagascar-a microcosm of the global tropics, covered in 80% grassy biomes-to illustrate how transdisciplinary approaches to research can clarify ecosystem dynamics, from evolutionary history to human land use. Research on Madagascar's human-environment interactions has sparked debates about the role of past and current land use in shaping grassy biomes (e.g., pastoralism, cultivation, fire use). These debates echo those in other regions globally, and highlight obstacles to understanding and supporting both ecosystem and livelihood resilience. Like many tropical biodiversity hotspots, Madagascar faces converging challenges that can be aided by transdisciplinary research, including food and health insecurity, economic inequities, biodiversity loss, climate change, land conversion, and limited resource access. We present a framework to guide transdisciplinary research centered on improved understanding and management of grassy biomes on Madagascar by: (1) establishing a globally common terminology; (2) summarizing data contributions and scientific knowledge gaps relating to Madagascar's grassy biomes; (3) identifying priority research questions for Madagascar with applicability in other regions; and (4) highlighting transdisciplinary, inclusive approaches to research that can co-benefit people and the ecosystems with which they interact
Setting stakeholder-led research priorities for advancing Sexual and Reproductive Health and Rights in Bangladesh using CHNRI method : an icddr,b initiative
No full textBackground Sexual and reproductive health and rights (SRHR) are essential for individuals' health, well-being, survival, and economic development. A stakeholder-led approach to research prioritisation was essential to guide SRHR-related research in Bangladesh. Accordingly, we conducted a research prioritisation exercise to identify health research priorities related to SRHR in Bangladesh. Methods We adopted the Child Health and Nutrition Research Initiative (CHNRI) method for this study. Five themes-adolescent Health (AH), fertility, gynaecological issues (GI), maternal and neonatal health (MNH), and SRH of key populations (SRHKP)-were selected from the broader field of SRHR. Seventy-six experts submitted 454 research questions (RQs), which were then condensed into 197 unique RQs and distributed to all experts for scoring based on five pre-selected criteria. Weighted and unweighted research priority scores (RPS) and average expert agreement (AEA) were calculated to compile a list of top-ranked RQs. Results The weighted RPSs for the 197 RQs ranged from 0.944 to 0.623, with a median of 0.848. Among the top 20 list, six RQs belonged to AH, one to Fertility, two to GI, six to MNH, and five to SRHKP. For AH, top ranked RQs included adolescent pregnancy, sexual health education, and mental health. Promoting proper birth spacing among newlywed and under-aged married women were top RQs for fertility. GI priorities emphasised early detection of gynaecological cancers, including HPV testing for cervical cancer screening. The MNH research focused on Newborn Stabilizing Units at sub-district hospitals, PPH bundle approaches, and counselling on danger signs to prevent adverse birth outcomes. The top-ranked RQs in SRHKP addressed stigma and discrimination towards key populations (KPs) and their impact on SRH behaviours. There was significant overlap between the top 20 RQs ranked by RPS and AEA. Conclusions The study emphasises the need for intervention research to address barriers, assess effectiveness, and enhance the uptake of evidence-based and innovative interventions for SRHR in Bangladesh
Measurements of WH and ZH production with Higgs boson decays into bottom quarks and direct constraints on the charm Yukawa coupling in 13 TeV pp collisions with the ATLAS detector
No full textA study of the Higgs boson decaying into bottom quarks (H → b¯b) and charmquarks (H → c¯c) is performed, in the associated production channel of the Higgs boson with aW or Z boson, using 140 fb−1 of proton-proton collision data at √s = 13 TeV collected by theATLAS detector. The individual production of W H and ZH with H → b¯b is established withobserved (expected) significances of 5.3 (5.5) and 4.9 (5.6) standard deviations, respectively.Differential cross-section measurements of the gauge boson transverse momentum withinthe simplified template cross-section framework are performed in a total of 13 kinematicalfiducial regions.The search for the H → c¯c decay yields an observed (expected) upper limit at 95%confidence level of 11.5 (10.6) times the Standard Model prediction. The results are also usedto set constraints on the charm coupling modifier, resulting in |κc| < 4.2 at 95% confidencelevel. Combining the H → b¯b and H → c¯c measurements constrains the absolute valueof the ratio of Higgs-charm and Higgs-bottom coupling modifiers (|κc/κb|) to be less than3.6 at 95% confidence levelFor complete list of authors see http://dx.doi.org/10.1007/JHEP04(2025)075</p
High-resolution seismic reflection surveying to delineate shallow subsurface geological structures in the karst area of Shenzhen, China
No full textNear-surface seismic reflection surveys can produce high-resolution geological structural images for engineering and hydrological investigations. To help delineate shallow subsurface complex geological structures in a karst area and to better understand limestone cave formation, a high-resolution 2D seismic reflection profile was acquired and processed in the urban area of Shenzhen, China. The stacked images detail subsurface structures down to depths of 80-90 m, including a concave shaped reflection that curves upwards, two thrusts and one normal fault, as well as a hard rock basement reflection at the southern end of the profile which could not be mapped by borehole investigations due to the limited drilling depth. Our interpretations correlate well with borehole data and were supported by synthetic seismic modelling. Limestone caves are mainly found along faults and near rivers in this area. The results provide new insight on the formation mechanism and distribution of the karst caves. Movement along faults and erosion generated fractures and fissures in the limestone that provide channels for rainwater and groundwater to circulate. These waters, rich in carbonic acid, dissolve minerals in the limestone, resulting in the formation of underground cavities
MII-polyphosphate-based wax-like material with osteogenesis and blood occlusion
No full textThere is a constant need for materials that combine hemostasis and osteogenesis in orthopedic surgery. Current hemostatic materials lack biodegradability, osteogenic properties, and hemostatic efficacy. In this study, we developed a wax-like co-doped polyphosphate (CoPPW) by chelating sodium polyphosphate with cationic ions (Ca2+, Mg2+, and Sr2+). Our results demonstrate that CoPPW was malleable and degraded optimally, releasing Mg2+ and Sr2+ ions initially and losing weight over 4 weeks. In vitro, CoPPW promoted better cell proliferation and osteogenic differentiation than beeswax, likely due to ion release. RT-PCR and transcriptome sequencing revealed that CoPPW significantly upregulated osteogenesis-related genes and bone-related protein expression. The activation of the PI3K/AKT signalling pathway confirmed osteogenesis, while the coagulation cascade pathway indicated effective hemostasis. In vivo, CoPPW was more effective in promoting bone regeneration and hemostasis compared to bone wax. Overall, CoPPW exhibits excellent hemostatic and osteogenic effects, making it a promising candidate for bone repair applications