Prime editing in zebrafish and Atlantic salmon : exploring a new CRISPR technique in non-mammalian species

The CRISPR-Cas system has enabled precise genome editing in a multitude of organisms, and gene knockout experiments can now be done with relative ease due to the simplicity of the system. However, unintended genomic side-effects of such editing have surfaced in the last couple of years. In this thesis, the CRISPR-based genome editing system prime editing was explored as an alternative gene knockout approach to avoid the unintended editing outcomes seen in the wake of regular CRISPR-Cas editing. Prime editing was applied to zebrafish (Danio rerio) by microinjection of RNP complexes and to Atlantic salmon (Salmo salar) cells by electroporation of plasmids and RNP complexes. No successful prime editing outcomes was observed in zebrafish. Low survival rate of both microinjected and uninjected embryos remained an obstacle throughout the project, and should be addressed before continuing zebrafish prime editing experiments. Prime editing of Atlantic salmon cells using plasmids did not produce any positive results. Prime editing with RNP complexes in Atlantic salmon cells showed signs of successful editing, but results remains inconclusive as further analysis is needed to properly validate the editing outcomes from this experiment.CRISPR-Cas har muliggjort presis redigering av genomer i en rekke organsimer, og kan brukes til å relativt enkelt slå ut gener for ulike formål. Til tross for at det er en presis og effektiv metode for genomredigering, har utilsiktede konsekvenser av bruk av CRISPRCas9 kommet til overflaten de siste årene. I denne oppgaven ble det CRISPR-baserte genomredigeringsverktøyet prime editing utforsket, for å se om det kan fungere som en alternativ metode for å slå ut gener og unngå de utilsiktede konsevensene som kan oppstå i kjølvannet av vanlig CRISPR-Casredigering. Prime editing ble brukt i zebrafisk (Danio rerio) ved mikroinjesering av RNP-komplekser og i lakseceller (Salmo salar), ved elektroporering av plasmider og RNP-komplekser. Bruk av prime editing i zebrafisk ga ingen positive resultater. Lav overlevelsesrate for både mikroinjesert fisk og uinjeserte kontroller var et vedvarende problem under prosjektet, og bør adresseres før videre forsøk med prime editing fortsetter. Prime editing-redigering av lakseceller ved elektroporering av plasmider ga ingen positive resultater. Resultatene fra prime editing-redigering med RNP-komplekser i lakseceller virker lovende, men det er for tidlig å kunne konkludere da videre analyser trengs for å kunne bekrefte resultatene.M-G

Rusmidler i Norge 2011

Rusmidler i Norge inneholder oppdaterte tabeller om forbruk, økonomi, kriminalitet, skadevirkninger og behandling knyttet både til alkohol-, narkotika-, legemiddel- og tobakksbruk. Nytt av året er blant annet tall fra sprøyterommet i Oslo. Utgitt i over 20 år Det er over 20 år siden den første utgaven av Rusmidler i Norge kom ut, og SIRUS har hvert år siden gitt ut et hefte med fersk rusmiddelstatistikk. Tallmaterialet er hentet fra offentlig statistikk og SIRUS´ egne undersøkelser. For å gjøre statistikken tilgjengelig i en internasjonal sammenheng, presenteres all tekst også på engelsk. RusStat - statistikk på nett Alle tabeller er også lagt ut i SIRUS´ nettbaserte statistikkdatabase - RusStat. Basen blir oppdatert etter hvert som nytt tallmateriale kommer inn. Her finnes også lengre tidsserier på mange områder, bl.a. omsetning av alkohol i Norge fra 1800-tallet til i dag

OpenIaC: open infrastructure as code - the network is my computer

Modern information systems are built fron a complex composition of networks, infrastructure, devices, services, and applications, interconnected by data flows that are often private and financially sensitive. The 5G networks, which can create hyperlocalized services, have highlighted many of the deficiencies of current practices in use today to create and operate information systems. Emerging cloud computing techniques, such as Infrastructure-as-Code (IaC) and elastic computing, offer a path for a future re-imagining of how we create, deploy, secure, operate, and retire information systems. In this paper, we articulate the position that a comprehensive new approach is needed for all OSI layers from layer 2 up to applications that are built on underlying principles that include reproducibility, continuous integration/continuous delivery, auditability, and versioning. There are obvious needs to redesign and optimize the protocols from the network layer to the application layer. Our vision seeks to augment existing Cloud Computing and Networking solutions with support for multiple cloud infrastructures and seamless integration of cloud-based microservices. To address these issues, we propose an approach named Open Infrastructure as Code (OpenIaC), which is an attempt to provide a common open forum to integrate and build on advances in cloud computing and blockchain to address the needs of modern information architectures. The main mission of our OpenIaC approach is to provide services based on the principles of Zero Trust Architecture (ZTA) among the federation of connected resources based on Decentralized Identity (DID). Our objectives include the creation of an open-source hub with fine-grained access control for an open and connected infrastructure of shared resources (sensing, storage, computing, 3D printing, etc.) managed by blockchains and federations. Our proposed approach has the potential to provide a path for developing new platforms, business models, and a modernized information ecosystem necessary for 5G networks.publishedVersio

Rusmidler i Norge 2009

Rusmidler i Norge inneholder oppdaterte tabeller om forbruk, økonomi, kriminalitet, skadevirkninger og behandling knyttet både til alkohol-, narkotika-, legemiddel- og tobakksbruk. Årets utgave er første gang der også tobakkstall er med i statistikkoversikten

Evaluating the Cloud-RAN architecture: functional splitting and switched Ethernet Xhaul

The Cloud-RAN architecture is a key enabler to building future mobile networks in a flexible and cost-efficient way. For instance, switched Ethernet is a prime candidate for mobile transport networks (Xhaul), due to its flexibility, ubiquity, and cost-effectiveness. Understanding its performance under different network configurations would allow concluding about its appeal for Cloud-RAN. On the other hand, evaluating resource sharing mechanisms is relevant to put in place best solutions to host multiple virtual Base Band Units (vBBUs) into the same compute infrastructure. This paper assesses the feasibility of using a switched Ethernet Xhaul, by instantiating two BBUsusing different functional splits. Moreover, this paper evaluates two mec general purpose server (GPS) hosting vBBUs. Our results point to a marginal performance degradation caused by the switched Ethernet Xhaul and the NIC sharing mechanisms. Such deviations could be seen from the increase in average and maximum Jitter and RTT results

Assessing the Cloud-RAN in the Linux Kernel: Sharing Computing and Network Resources

Cloud-based Radio Access Network (Cloud-RAN) leverages virtualization to enable the coexistence of multiple virtual Base Band Units (vBBUs) with collocated workloads on a single edge computer, aiming for economic and operational efficiency. However, this coexistence can cause performance degradation in vBBUs due to resource contention. In this paper, we conduct an empirical analysis of vBBU performance on a Linux RT-Kernel, highlighting the impact of resource sharing with user-space tasks and Kernel threads. Furthermore, we evaluate CPU management strategies such as CPU affinity and CPU isolation as potential solutions to these performance challenges. Our results highlight that the implementation of CPU affinity can significantly reduce throughput variability by up to 40%, decrease vBBU’s NACK ratios, and reduce vBBU scheduling latency within the Linux RT-Kernel. Collectively, these findings underscore the potential of CPU management strategies to enhance vBBU performance in Cloud-RAN environments, enabling more efficient and stable network operations. The paper concludes with a discussion on the efficient realization of Cloud-RAN, elucidating the benefits of implementing proposed CPU affinity allocations. The demonstrated enhancements, including reduced scheduling latency and improved end-to-end throughput, affirm the practicality and efficacy of the proposed strategies for optimizing Cloud-RAN deployments

Opportunistic CPU Sharing in Mobile Edge Computing Deploying the Cloud-RAN

Leveraging virtualization technology, Cloud-RAN deploys multiple virtual Base Band Units (vBBUs) along with collocated applications on the same Mobile Edge Computing (MEC) server. However, the performance of real-time (RT) applications such as the vBBU could potentially be impacted by sharing computing resources with collocated workloads. To address this challenge, this paper presents a dynamic CPU sharing mechanism, specifically designed for containerized virtualization in MEC servers, that hosts both RT and non-RT general-purpose applications. Initially, the CPU sharing problem in MEC servers is formulated as a Mixed-Integer Programming (MIP). Then, we present an algorithmic solution that breaks down the MIP into simpler subproblems that are then solved using efficient, constant factor heuristics. We assessed the performance of this mechanism against instances of a commercial solver. Further, via a small-scale testbed, we assessed various CPU sharing mechanisms and their effectiveness in reducing the impact of CPU sharing indicate that our CPU sharing mechanism reduces the worstcase execution time by more than 150% compared to the default host RT-Kernel approach. This evidence is strengthened when evaluating this mechanism within Cloud-RAN, in which vBBUs share resources with collocated applications on a MEC server. Using our CPU sharing approach, the vBBU’s scheduling latency decreases by up to 21% in comparison with the host RT-Kernel

The great eclogite debate of the Western Gneiss Region, Norwegian Caledonides: The in situ crustal v. exotic mantle origin controversy

An entertaining debate arose in the latter half of the 20th century among scientists working on the spectacular eclogite facies rocks that occur within metamorphic rocks of the Western Gneiss Region (WGR) of the Norwegian Caledonides. It resulted in part from Eskola's influential publication “On the Eclogites of Norway” who concluded, incorrectly, that mafic eclogites within gneisses (external eclogites) and garnetiferous ultramafic rocks within peridotite lenses had a common origin. The debate featured two end‐member positions. One was that all these garnet‐bearing assemblages, regardless of association, had an exotic origin, where they recrystallized at extremely high pressures and temperatures (P–T) in the mantle and then were tectonically inserted upward into the crust. The other was the in situ origin where this recrystallization occurred within the enclosing gneisses during regional metamorphism. Garnet peridotites and pyroxenites have compositions identical to ultramafic xenoliths in kimberlites and define P–T conditions that are appropriate to the upper mantle. Therefore, peridotite lenses were generally (and correctly) interpreted to be mantle fragments. However, some extended this exotic origin to external eclogites, particularly coarse‐grained orthopyroxene‐ (and coesite‐) bearing eclogites, which also formed at extremely high P–T. They noted an apparent pressure and temperature disequilibrium between anhydrous eclogites and the surrounding amphibolite facies gneisses. It was generally accepted that eclogites could form only in “dry” environments (urn:x-wiley:02634929:media:jmg12314:jmg12314-math-0001 << Ptotal). Thus, eclogites had to form within the anhydrous mantle rather than the host hydrous crust. Finally, there was doubt as to whether the necessary P–T conditions could be generated in continental crust, even when tectonically thickened. The arguments for an in situ origin were based largely on external eclogites. Thin sections showed garnet cores with amphibolite facies inclusions and rims with eclogite facies minerals suggesting prograde metamorphism. Similarly, core to rim changes in mineral chemical composition were consistent with increasing P–T. Coesite and microdiamond were found in both eclogites and host gneisses. Finally, thermobarometry showed burial depths increased from SE to NW across the WGR. Breakthroughs occurred when old assumptions were discarded. Eclogite recrystallization actually can occur in the presence of water. Eclogites and garnet peridotite and pyroxenites had completely different histories. They give different ages, formed under different P–T conditions, and have different geochemical fingerprints. The debate was finally resolved when it became generally accepted that continental crust could subduct into the mantle. Thus, it could subduct to eclogite facies depths where, simultaneously, peridotites could be inserted from the overlying mantle wedge. Both sides of the debate were correct! However, eclogites recrystallized “in situ” only because the enclosing crust was deep in the mantle and garnet peridotites did invade continental crust as solids, but only because the crust was below a mantle wedge. The “Great Debate” was fierce at times, but it led to the modern understanding that continental subduction is a vital part of mountain building

PRINCIPIA: Opportunistic CPU and CPU-shares Allocation for Containerized Virtualization in Mobile Edge Computing

Leveraging virtualization technology, Mobile Edge Computing (MEC) deploys multiple services with different execution time requirements running as isolated processes. For instance, both real-time (RT) and non-RT applications may be (are) running on the same infrastructure using containerized virtualization. Nevertheless, sharing resources (e.g., CPU) with collocated workloads could impact the RT performance of RT applications. This paper presents PRINCIPIA, a dynamic CPU and CPU-shares allocation mechanism that opportunistically enables non-RT applications to run on underutilized CPUs while providing RT guarantees to RT applications. By monitoring MEC’s system metrics like processor’s CPU utilization and container’s CPU usage, PRINCIPIA dynamically allocates both CPU and CPU-shares to containers running non-RT applications aiming at opportunistically exploiting underutilized CPUs by containers running RT applications. We evaluate PRINCIPIA on a small-scale MEC server which uses containerized virtualization along with Linux RT Kernel to deploy both RT and non-RT applications. Our findings show that PRINCIPIA mitigates the impact on the RT performance of RT applications providing bounded processing latency in comparison with the default host Kernel scheduler

Recycling Argon through Metamorphic Reactions: the Record in Symplectites

The 40Ar/39Ar ages of metamorphic micas that crystallized at high temperatures are commonly interpreted as cooling ages, with grains considered to have lost 40Ar via thermally-driven diffusion into the grain boundary network. Recently reported laser-ablation data suggest that the spatial distribution of Ar in metamorphic micas does not always conform to the patterns predicted by diffusion theory and that despite high metamorphic temperatures, argon was not removed efficiently from the local system during metamorphic evolution. In the Western Gneiss Region (WGR), Norway, felsic gneisses preserve microtextural evidence for the breakdown of phengite to biotite and plagioclase symplectites during near isothermal decompression from c. 20–25 to c. 8–12 kbar at ~700°C. These samples provide an ideal natural laboratory to assess whether the complete replacement of one K-bearing mineral by another at high temperatures completely ‘resets’ the Ar clock, or whether there is some inheritance of 40Ar in the neo-crystallized phase. The timing of the high-temperature portion of the WGR metamorphic cycle has been well constrained in previous studies. However, the timing of cooling following the overprint is still much debated. In-situ laser ablation spot dating in phengite, biotite-plagioclase symplectites and coarser, texturally later biotite yielded 40Ar/39Ar ages that span much of the metamorphic cycle. Together these data show that despite residence at temperatures of ~700°C, Ar is not completely removed by diffusive loss or during metamorphic recrystallization. Instead, Ar released during phengite breakdown appears to be partially reincorporated into the newly crystallizing biotite and plagioclase (or is trapped in fluid inclusions in those phases) within a close system. Our data show that the microtextural and petrographic evolution of the sample being dated provides a critical framework in which local 40Ar recycling can be tracked, thus potentially allowing 40Ar/39Ar dates to be linked more accurately to metamorphic history