Publikationer från Uppsala Universitet
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Climate Impacts on Conflict : The Role of Water
No full textChapter III examines how climate change and water scarcity drive conflict by increasing competition and vulnerability, particularly in fragile regions. It shows that armed conflict further damages water resources, worsening crisis for vulnerable groups. While water scarcity can fuel violence and unrest, strong governance and inclusive managment can reduce these risks. The chapter highlights the need for integrated water governance and peacebuidling to address the climate-water-conflict nexus
Structure-based discovery of positive allosteric modulators of the A1 adenosine receptor
No full textAllosteric modulation of G protein–coupled receptors (GPCRs) is an exciting strategy for developing new therapeutic agents, and it has several advantages over more commonly used orthosteric drugs. Recently determined GPCR structures have revealed allosteric pockets facing the lipid bilayer, enabling rational drug design. Here, we develop a virtual screening strategy to discover ligands of extrahelical binding pockets and apply this approach to the adenosine A1 receptor (A1R). The A1R is a high-value therapeutic target for ischemia–reperfusion injury and chronic neuropathic pain. Developing effective A1R therapeutics remains challenging due to high structural conservation across orthosteric binding sites and on-target unwanted effects stimulated by prototypical A1R agonists, such as bradycardia and atrioventricular block. However, A1R positive allosteric modulators (PAMs) acting through spatially distinct allosteric sites can fine-tune A1R activity with high subtype selectivity and spatiotemporal specificity, thereby overcoming current limitations. A chemical library of 160 million compounds was computationally docked to the allosteric pocket identified in a cryo-EM structure of the A1R, and a set of 26 top-ranked compounds were selected for experimental evaluation. Pharmacological evaluation of these, and structure-guided hit optimization, led to the discovery of subtype-selective A1R PAMs. These compounds demonstrated minimal allosteric agonism and negligible impact on A1R-mediated beat rate of an orthosteric agonist. The discovered PAMs pave the way for potential treatments for neuropathic pain and ischemia–reperfusion injury without accompanying side effects. Our results demonstrate the utility of a synergistic computational and experimental approach in GPCR drug discovery.De två första författarna delar förstaförfattarskapet</p
Spectroscopic and Photometric Analysis of Globular Clusters in nearby Dwarf Galaxies
No full textGlobular clusters (GCs) are typically observed in massive galaxies and, owing to their old ages (≥10 Gyr), are often regarded as relics of early galaxy formation. However, dwarf galaxies can also host GCs, including younger or intermediate-age populations. In this study, we investigate GCs in seven nearby star-forming dwarf galaxies (5–12 Mpc) using integral field spectroscopy from the Multi Unit Spectroscopic Explorer (MUSE) and archival imaging from the Hubble Space Telescope (HST). We identify a total of 47 GC candidates in five of the galaxies, and derive their velocities, ages, metallicities, photometric masses, and optical colours. The majority of our candidates show young ages (<12 Gyr) and low metallicities ([M/H] ≲ −0.5), consistent with the expected chemical evolution of low-mass galaxies. Their photometric masses span log10(M) = 4.6–7.0, with more massive clusters preferentially found in the more distant galaxies. Compared to M31 GCs, our candidates appear systematically bluer in V −I, which may reflect intrinsic differences in stellar populations or biases introduced by our conservative selection criteria. This work contributes to the still limited sample of young GC populations in star-forming dwarf galaxies, and highlights the importance of combining spectroscopy and space-based imaging to robustly identify and characterize such clusters. Our results support the idea that GCs can form in a variety of environments and at later cosmic times than traditionally assumed
Optimization of the goods reception at a production unit
No full textOsäkerheter i omvärlden sätter högre press på flexibilitet och redundans i försörjningskedjor.För att kunna säkerställa en fortsatt konkurrenskraft behöver företag anpassa sinlagerverksamhet för att kunna hantera oförutsägbara behov. Detta arbete kommer fokusera påatt optimera ett företags godsmottagningsprocess för att kunna hantera volymvariationer.Optimering av en godsmottagningsprocess kan uppnås genom en automatiseringslösning iform av AGV:er. För att kunna möta dagens och framtidens krav är det grundläggande attföretaget förstår de parametrar som är centrala för att på ett effektivt sätt automatiserahanteringen av inkommande gods. Frågeställningarna grundas utifrån identifiering ochimplementering av lösningar för att effektivisera godsmottagningen och därmed uppnå bättrevolym- och kapacitetshantering.För att besvara frågeställningarna används kvalitativa och kvantitativa metoder. Dessa bestårav observationer och intervjuer, datainsamling från företagets interna databas samt litteratur-och tidsstudier. Datan analyserades till sist i ett simulationsprogram för att generera framtidalösningar.Resultatet visar att en AGV-baserad automationslösning leder till kostnadsreduceringar somhanterar högre volymvariationer. Resultatet presenterar även vad som krävs vidimplementeringen av en automationslösning. Dessa består av en standardiseradinlastningsprocess, minimering av kötid samt en minskning av manuella arbetare. Till sistpresenteras en framtida layout samt tre lösningsförslag som fokuserar på att minimeraväntetid för lastbil, ledtid för godset samt tiden manuella arbetare behöver vänta påkommande steg i processen.Det framgår att en buffert framför AGV:erna krävs för ett fungerande processflöde, vilketsäkerställs genom ett rullband. Det nya processflödet leder till reducering av ledtid ochlastbilsväntan. Lösningen som tas fram ses uppfylla arbetets syfte.Uncertainties in the society are placing higher demands on flexibility and redundancy in supplychains. To ensure continued competitiveness, companies need to adapt their inventory operationsto handle unpredictable demands. This work focuses on optimizing a company's goods receivingprocess to manage volume variations. Optimization of a goods receiving process can be achievedthrough an automation solution in the form of AGVs. To meet the demands, it is essential thatthe company understands the parameters that are central to effectively automate the handling ofincoming goods. The issues posed are based on the identification and implementation ofsolutions to streamline goods receiving and thus achieve better volume and capacitymanagement. To answer these questions, qualitative and quantitative methods are used. Theseconsist of observations and interviews, data collection from the company's internal database aswell as literature and time studies. The data was then analyzed in a simulation program in orderto develop future solutions. The results show that an AGV-based automation solution leads toreduced costs that can manage higher volume variations. The results also present what isrequired for the implementation of an automation solution. These consist of a standardizedloading process, minimization of waiting time, and a reduction of manual workers. Finally, afuture layout and three solution proposals are presented that focus on minimizing truck waitingtime, lead time for goods, and the time manual workers need to wait for the next steps in theprocess. It is evident that a buffer in front of the AGVs is required for a functioning processflow, which is ensured through a conveyor belt. The new process flow leads to a reduction inlead time and the waiting time for the freight trucks
Black hole singularities from holographic complexity
No full textUsing a second law of complexity, we prove a black hole singularity theorem. By introducing the notion of trapped extremal surfaces, we show that their existence implies null geodesic incompleteness inside globally hyperbolic black holes. We also demonstrate that the vanishing of the growth rate of the volume of extremal surfaces provides a sharp diagnostic of the black hole singularity. In static, uncharged, spherically symmetric spacetimes, this corresponds to the growth rate of spacelike extremal surfaces going to zero at the singularity. In charged or rotating spacetimes, such as the Reissner-Nordstr & ouml;m and Kerr black holes, we identify novel timelike extremal surfaces that exhibit the same behavior at the timelike singularity
En avbruten episod av keramikframställning? Studie av stenålderskeramik i Dalarna : Rapport över registrering och analyser av keramik från GRK-boplatser vid Korsnäset och Orsandbaden
No full textBeing literate in data or practices : how paradata functions in the context of literacy
No full textIntroduction. Datafication of information practices underlines the importance of better understanding of data literacy and documentation. Framing data literacy as a sociocultural information practice, we draw from its conceptual affinities with the notion paradata to advance the understanding what it takes to be(come) literate, and how paradata functions in the context of literacy. Method. Theoretical discussion draws from an interviews with (N=) 33 professionals working with archaeological data. Analysis. Interview transcripts were analysed using a method based on the constant comparative method and close reading. Results. Four facets of being literate with archaeological data were identified: information making literacy, syntactic literacy, information taking literacy and interpretative literacy. Becoming literate is influenced by the parallel (in)adequacy of individual facets. Literacies’ social being-in-making makes becoming literate hard. Finally, paradata potentially 1) contributes developing and enacting individual literacies, 2) catalysing and impeding convergence of literacies, and 3) enacting the contexts of literacies. Conclusions. Paradata, as a concept referring to practice-related meta-information, provides means to operationalise what can be known and communicated about practices as a contextual constituent of literacy. Paradata helps in becoming and staying literate. Finally, literacy can be a question of competent practice with paradata rather than mastering the data itself
The art and politics of micronational language planning
No full textThis article discusses the language politics of micronations. It argues that micronational language planning offers a three-pronged satirical rejoinder to mainstream language politics. First, micronational language politics pushes back at attempts to frame nation-states and national languages as irrelevant in a globalized world. Second, it rebuffs neo-romantic sociolinguistic critiques of globalization. Third, it troubles technocratic approaches to language policy and planning (LPP). This argument is grounded in a close analysis of two micronational art projects: Elgaland-Vargaland and Ladonia. These micronations simultaneously appropriate and debase traditional LPP, creating both a defamiliarization of well-worn language ideologies and a destabilization of technocratic linguistic expertise. This is a promising starting point for reimagining research into the politics of language
Bioinformatic analysis of knocking down the Gaucher and Fabry disease causing genes in a well validated primary cell model
No full textLysosomal storage disorders (LSDs) are a type of inherited metabolic diseases (IMDs) that are caused mostly by deficiencies in the lysosomal enzymes leading to the accumulation of their substrates in cells and organs. Gaucher and Fabry diseases are two types of LSDs that affect the handling of lipid substances (sphingolipids). It is well known that Gaucher disease has a bone phenotype, and recently, studies have found that Fabry disease also affects bone, but this is less well studied. In addition, there are studies focusing on how LSDs affect energy metabolism. This hypothesis generating study aims to identify similarities and differences that may point to common and unique cellular mechanisms of these diseases on bone and identify potential pathways, upstream regulators, and cellular functions that can explain the effect of the diseases on bone and give an insight into any alternative metabolic energy pathways used. The Ingenuity Pathway Analysis (IPA®, QIAGEN Redwood City) software package was used to analyse RNA sequencing data of bone cells where the disease-causing genes for Gaucher and Fabry disease had been knocked down using siRNAs. Key findings reveal the most enriched pathways in Gaucher to be (a) Expression and translocation of olfactory receptors, (b) Keratinization and (c) Hepatic fibrosis. While the most enriched pathways in Fabry are (a) Interferon alpha/beta signalling, (b) Role of hypercytokinemia in the pathogenesis of influenza and (c) OAS antiviral response. The upstream analysis and toxicity list indicate that there are distinct and opposing regulatory pathways between the datasets. Fabry disease is an X-linked disease, with males being more affected. Gender comparisons in Fabry revealed the following pathways, (a) IL-15 production, (b) Colorectal cancer metastasis signalling, (c) Interferon alpha/beta signalling, and (d) Role of hypercytokinemia in the pathogenesis of influenza differing between males and females. The toxicity list which is a prediction of the toxic effects that may result from changes in the gene expression, revealed cardiac hypertrophy as highly significant in the female. Novel upstream regulators that may be involved in influencing disease mechanisms, not previously linked to Fabry or Gaucher disease were identified. In summary, the findings indicate that distinct and overlapping molecular mechanisms and metabolic energy pathways may be involved in Fabry and Gaucher disease, offering a foundation for future studies aimed at understanding the broader implications of lysosomal storage disorders across different cell types and tissues
Bridging Migrants' Social Protection Gap : Understanding the Incomplete Revolution of International Social Security Coordination
No full textRecent decades have seen a sharp but regionally imbalanced expansion of bilateral and multilateral social security agreements (SSAs), which serve to bridge gaps in migrant workers' social protection by facilitating international portability of social rights and benefits. However, our knowledge about the factors shaping this remarkable, yet puzzling, development remains scarce. This study integrates literatures on international cooperation and the migration-welfare state nexus to formulate theoretical expectations about how migration patterns interact with democracy, economic development, and social security design to shape countries' SSA trajectories. The authors analyze a new global dyadic data set that covers almost 1,300 SSA adoptions throughout the post-World War II period. They find that a country-pair's level of development and similarity with regard to these three factors help to account for the countries' likelihood of establishing an SSA, with migration working as a demand driver. These findings help to explain gaps in social protection between migrants and native residents worldwide and suggest how those gaps may be bridged