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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Richards, Stephen, et al.
(författare)
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Genome Sequence of the Pea Aphid Acyrthosiphon pisum
- 2010
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
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Tidskriftsartikel (refereegranskat)abstract
- Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
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| 4. |
- Abbasi, Rasha, et al.
(författare)
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IceCube search for neutrinos from GRB 221009A
- 2023
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Ingår i: Proceedings of 38th International Cosmic Ray Conference (ICRC 2023). - : Sissa Medialab Srl.
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Konferensbidrag (refereegranskat)abstract
- GRB 221009A is the brightest Gamma Ray Burst (GRB) ever observed. The observed extremelyhigh flux of high and very-high-energy photons provide a unique opportunity to probe the predictedneutrino counterpart to the electromagnetic emission. We have used a variety of methods to searchfor neutrinos in coincidence with the GRB over several time windows during the precursor, promptand afterglow phases of the GRB. MeV scale neutrinos are studied using photo-multiplier ratescalers which are normally used to search for galactic core-collapse supernovae neutrinos. GeVneutrinos are searched starting with DeepCore triggers. These events don’t have directionallocalization, but instead can indicate an excess in the rate of events. 10 GeV - 1 TeV and >TeVneutrinos are searched using traditional neutrino point source methods which take into accountthe direction and time of events with DeepCore and the entire IceCube detector respectively. The>TeV results include both a fast-response analysis conducted by IceCube in real-time with timewindows of T0 − 1 to T0 + 2 hours and T0 ± 1 day around the time of GRB 221009A, as well asan offline analysis with 3 new time windows up to a time window of T0 − 1 to T0 + 14 days, thelongest time period we consider. The combination of observations by IceCube covers 9 ordersof magnitude in neutrino energy, from MeV to PeV, placing upper limits across the range forpredicted neutrino emission.
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| 5. |
- Baetz, Konstantin, et al.
(författare)
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Challenging the Status Quo : Predicting Violence with Sparse Decision-Making Data
- 2022
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Ingår i: International Interactions. - : Taylor & Francis. - 0305-0629 .- 1547-7444. ; 48:4, s. 697-713
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Tidskriftsartikel (refereegranskat)abstract
- This article addresses the discrepancy between the explanation and the prediction of political violence through the development of different models that approximate the decision-making on war and peace. Borrowing from the crisis bargaining literature, the prediction models particularly consider the situational attributes through which players can challenge the status quo. We distinguish between direct and indirect proxies of a weakening of the status quo and show that adding decision-making data can improve the accuracy of cross-sectional forecasting models. The study, which demonstrates the increased conflict risk due to the COVID-19 pandemic and thus another development upsetting the status quo, discusses the usefulness of decision-making forecasts through various case study illustrations.
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| 6. |
- Billker, Oliver, et al.
(författare)
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Distinct mechanisms of internalization of Neisseria gonorrhoeae by members of the CEACAM receptor family involving Rac1- and Cdc42-dependent and -independent pathways
- 2002
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Ingår i: EMBO Journal. - : European Molecular Biology Organization. - 0261-4189 .- 1460-2075. ; 21:4, s. 560-571
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Tidskriftsartikel (refereegranskat)abstract
- Opa adhesins of pathogenic Neisseria species target four members of the human carcinoembryonic antigen-related cellular adhesion molecule (CEACAM) family. CEACAM receptors mediate opsonization-independent phagocytosis of Neisseria gonorrhoeae by human granulocytes and each receptor individually can mediate gonococcal invasion of epithelial cells. We show here that gonococcal internalization occurs by distinct mechanisms depending on the CEACAM receptor expressed. For the invasion of epithelial cell lines via CEACAM1 and CEACAM6, a pathogen-directed reorganization of the actin cytoskeleton is not required. In marked contrast, ligation of CEACAM3 triggers a dramatic but localized reorganization of the host cell surface leading to highly efficient engulfment of bacteria in a process regulated by the small GTPases Rac1 and Cdc42, but not Rho. Two tyrosine residues of a cytoplasmic immune receptor tyrosine-based activating motif of CEACAM3 are essential for the induction of phagocytic actin structures and subsequent gonococcal internalization. The granulocyte-specific CEACAM3 receptor has properties of a single chain phagocytic receptor and may thus contribute to innate immunity by the elimination of Neisseria and other CEACAM-binding pathogens that colonize human mucosal surfaces.
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| 7. |
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| 8. |
- Hegre, Håvard, 1964-, et al.
(författare)
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ViEWS : A political violence early-warning system
- 2019
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Ingår i: Journal of Peace Research. - : SAGE Publications. - 0022-3433 .- 1460-3578. ; 56:2, s. 155-174
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Tidskriftsartikel (refereegranskat)abstract
- This article presents ViEWS – a political violence early-warning system that seeks to be maximally transparent, publicly available, and have uniform coverage, and sketches the methodological innovations required to achieve these objectives. ViEWS produces monthly forecasts at the country and subnational level for 36 months into the future and all three UCDP types of organized violence: state-based conflict, non-state conflict, and one-sided violence in Africa. The article presents the methodology and data behind these forecasts, evaluates their predictive performance, provides selected forecasts for October 2018 through October 2021, and indicates future extensions. ViEWS is built as an ensemble of constituent models designed to optimize its predictions. Each of these represents a theme that the conflict research literature suggests is relevant, or implements a specific statistical/machine-learning approach. Current forecasts indicate a persistence of conflict in regions in Africa with a recent history of political violence but also alert to new conflicts such as in Southern Cameroon and Northern Mozambique. The subsequent evaluation additionally shows that ViEWS is able to accurately capture the long-term behavior of established political violence, as well as diffusion processes such as the spread of violence in Cameroon. The performance demonstrated here indicates that ViEWS can be a useful complement to non-public conflict-warning systems, and also serves as a reference against which future improvements can be evaluated.
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| 9. |
- Katsikas, Georgios P., 1987-
(författare)
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NFV Service Chains at the Speed of the Underlying Commodity Hardware
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Link speeds in networks will in the near-future reach and exceed 100 Gbps. While available specialized hardware can accommodate these speeds, modern networks have adopted a new networking paradigm, also known as Network Functions Virtualization (NFV), that replaces expensive specialized hardware with open-source software running on commodity hardware. However, achieving high performance using commodity hardware is a hard problem mainly because of the processor-memory gap. This gap suggests that only the fastest memories of today’s commodity servers can achieve the desirable access latencies for high speed networks. Existing NFV systems realize chained network functions (also known as service chains) mostly using slower memories; this implies a need for multiple additional CPU cores or even multiple servers to achieve high speed packet processing. In contrast, this thesis combines four contributions to realize NFV service chains with dramatically higher performance and better efficiency than the state of the art.The first contribution is a framework that profiles NFV service chains to uncover reasons for performance degradation, while the second contribution leverages the profiler’s data to accelerate these service chains by combining multiplexing of system calls with scheduling strategies. The third contribution synthesizes input/output and processing service chain operations to increase the spatial locality of network traffic with respect to a system’s caches. The fourth contribution combines the profiler’s insights from the first contribution and the synthesis approach of the third contribution to realize NFV service chains at the speed of the underlying commodity hardware. To do so, stateless traffic classification operations are offloaded into available hardware (i.e., programmable switches and/or network cards) and a tag is associated with each traffic class. At the server side, input traffic classes are classified by the hardware based upon the values of these tags, which indicate the CPU core that should undertake their stateful processing, while ensuring zero inter-core communication.With commodity hardware, this thesis realizes Internet Service Provider-level service chains and deep packet inspection at a line-rate 40 Gbps and stateful service chains at the speed of a 100 GbE network card on a 16 core single server. This results in up to (i) 4.7x lower latency, (ii) 8.5x higher throughput, and (iii) 6.5x better efficiency than the state of the art. The techniques described in this thesis are crucial for realizing future high speed NFV deployments.
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| 10. |
- Katsikas, Georgios P., 1987-
(författare)
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Realizing High Performance NFV Service Chains
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Network functions (NFs) hold a key role in networks, offering in-network services, such as enhanced performance, policy enforcement, and security. Traditionally, NFs have been implemented in specialized, thus expensive hardware. To lower the costs of deploying NFs, network operators have adopted network functions virtualization (NFV), by migrating NFs from hardware to software running in commodity servers. Several approaches to NFV have shown that commodity network stacks and drivers (e.g., Linux-based) struggle to keep up with increasing hardware speed. Despite this, popular networking services still rely on these commodity components. Moreover, chaining NFs (also known as service chaining) is challenging due to redundancy in the elements of the chain. This licentiate thesis addresses the performance problems of NFV service chains.The first contribution is a framework that (i) profiles NFV service chains to uncover performance degradation reasons and (ii) leverages the profiler’s data to accelerate these chains, by combining multiplexing of system calls with scheduling strategies. These accelerations improve the cache utilization and thereby the end-to-end latency of chained NFs is reduced by a factor of three. Moreover, the same chains experience a multi-fold latency variance reduction; this result improves the quality of highly-interactive services.The second contribution of this thesis substantially revises the way NFV service chains are realized. NFV service chains are synthesized while eliminating redundant input/output and repeated elements, providing consolidated stateful cross layer packet operations across the chain. This software-based synthesis achieves line-rate 40 Gbps throughput for stateful and long service chains. This performance is 8.5x higher than the performance achieved by the software-based state of the art FastClick framework. Experiments with three example Internet Service Provider-level service chains show that this synthesis approach operates at 40 Gbps, when the classification of these chains is offloaded to an OpenFlow switch.
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