| 21. |
- Chen, Gang, et al.
(författare)
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On the kinematic algebra for BCJ numerators beyond the MHV sector
- 2019
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Ingår i: Journal of High Energy Physics (JHEP). - : Springer. - 1126-6708 .- 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The duality between color and kinematics present in scattering amplitudes of Yang-Mills theory strongly suggests the existence of a hidden kinematic Lie algebra that controls the gauge theory. While associated BCJ numerators are known on closed forms to any multiplicity at tree level, the kinematic algebra has only been partially explored for the simplest of four-dimensional amplitudes: up to the MHV sector. In this paper we introduce a framework that allows us to characterize the algebra beyond the MHV sector. This allows us to both constrain some of the ambiguities of the kinematic algebra, and better control the generalized gauge freedom that is associated with the BCJ numerators. Specifically, in this paper, we work in dimension-agnostic notation and determine the kinematic algebra valid up to certain ? ((epsilon i .epsilon j )(2)) terms that in four dimensions compute the next-to-MHV sector involving two scalars. The kinematic algebra in this sector is simple, given that we introduce tensor currents that generalize standard Yang-Mills vector currents. These tensor currents control the generalized gauge freedom, allowing us to generate multiple different versions of BCJ numerators from the same kinematic algebra. The framework should generalize to other sectors in Yang-Mills theory.
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| 22. |
- Chen, Gang, et al.
(författare)
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Utilization-Based Scheduling of Flexible Mixed-Criticality Real-Time Tasks
- 2018
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Ingår i: IEEE Transactions on Computers. - : IEEE COMPUTER SOC. - 0018-9340 .- 1557-9956. ; 67:4, s. 543-558
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Tidskriftsartikel (refereegranskat)abstract
- Mixed-criticality models are an emerging paradigm for the design of real-time systems because of their significantly improved resource efficiency. However, formal mixed-criticality models have traditionally been characterized by two impractical assumptions: once any high-criticality task overruns, all low-criticality tasks are suspended and all other high-criticality tasks are assumed to exhibit high-criticality behaviors at the same time. In this paper, we propose a more realistic mixed-criticality model, called the flexible mixed-criticality (FMC) model, in which these two issues are addressed in a combined manner. In this new model, only the overrun task itself is assumed to exhibit high-criticality behavior, while other high-criticality tasks remain in the same mode as before. The guaranteed service levels of low-criticality tasks are gracefully degraded with the overruns of high-criticality tasks. We derive a utilization-based technique to analyze the schedulability of this new mixed-criticality model under EDF-VD scheduling. During run time, the proposed test condition serves an important criterion for dynamic service level tuning, by means of which the maximum available execution budget for low-criticality tasks can be directly determined with minimal overhead while guaranteeing mixed-criticality schedulability. Experiments demonstrate the effectiveness of the FMC scheme compared with state-of-the-art techniques.
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| 23. |
- Davidsson, Marcus, et al.
(författare)
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A novel process of viral vector barcoding and library preparation enables high-diversity library generation and recombination-free paired-end sequencing
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Detailed characterization and mapping of oligonucleotide function in vivo is generally a very time consuming effort that only allows for hypothesis driven subsampling of the full sequence to be analysed. Recent advances in deep sequencing together with highly efficient parallel oligonucleotide synthesis and cloning techniques have, however, opened up for entirely new ways to map genetic function in vivo. Here we present a novel, optimized protocol for the generation of universally applicable, barcode labelled, plasmid libraries. The libraries are designed to enable the production of viral vector preparations assessing coding or non-coding RNA function in vivo. When generating high diversity libraries, it is a challenge to achieve efficient cloning, unambiguous barcoding and detailed characterization using low-cost sequencing technologies. With the presented protocol, diversity of above 3 million uniquely barcoded adeno-associated viral (AAV) plasmids can be achieved in a single reaction through a process achievable in any molecular biology laboratory. This approach opens up for a multitude of in vivo assessments from the evaluation of enhancer and promoter regions to the optimization of genome editing. The generated plasmid libraries are also useful for validation of sequencing clustering algorithms and we here validate the newly presented message passing clustering process named Starcode.
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| 24. |
- Davidsson, Marcus, et al.
(författare)
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A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 116:52, s. 27053-27062
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Tidskriftsartikel (refereegranskat)abstract
- Adeno-associated virus (AAV) capsid modification enables the generation of recombinant vectors with tailored properties and tropism. Most approaches to date depend on random screening, enrichment, and serendipity. The approach explored here, called BRAVE (barcoded rational AAV vector evolution), enables efficient selection of engineered capsid structures on a large scale using only a single screening round in vivo. The approach stands in contrast to previous methods that require multiple generations of enrichment. With the BRAVE approach, each virus particle displays a peptide, derived from a protein, of known function on the AAV capsid surface, and a unique molecular barcode in the packaged genome. The sequencing of RNA-expressed barcodes from a single-generation in vivo screen allows the mapping of putative binding sequences from hundreds of proteins simultaneously. Using the BRAVE approach and hidden Markov model-based clustering, we present 25 synthetic capsid variants with refined properties, such as retrograde axonal transport in specific subtypes of neurons, as shown for both rodent and human dopaminergic neurons.
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| 25. |
- Davidsson, Marcus, et al.
(författare)
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Molecular barcoding of viral vectors enables mapping and optimization of mRNA trans-splicing
- 2018
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Ingår i: RNA. - : Cold Spring Harbor Laboratory. - 1355-8382 .- 1469-9001. ; 24:5, s. 673-687
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Tidskriftsartikel (refereegranskat)abstract
- Genome editing has proven to be highly potent in the generation of functional gene knockouts in dividing cells. In the CNS however, efficient technologies to repair sequences are yet to materialize. Reprogramming on the mRNA level is an attractive alternative as it provides means to perform in situ editing of coding sequences without nuclease dependency. Furthermore, de novo sequences can be inserted without the requirement of homologous recombination. Such reprogramming would enable efficient editing in quiescent cells (e.g., neurons) with an attractive safety profile for translational therapies. In this study, we applied a novel molecular-barcoded screening assay to investigate RNA trans-splicing in mammalian neurons. Through three alternative screening systems in cell culture and in vivo, we demonstrate that factors determining trans-splicing are reproducible regardless of the screening system. With this screening, we have located the most permissive trans-splicing sequences targeting an intron in the Synapsin I gene. Using viral vectors, we were able to splice full-length fluorophores into the mRNA while retaining very low off-target expression. Furthermore, this approach also showed evidence of functionality in the mouse striatum. However, in its current form, the trans-splicing events are stochastic and the overall activity lower than would be required for therapies targeting loss-of-function mutations. Nevertheless, the herein described barcode-based screening assay provides a unique possibility to screen and map large libraries in single animals or cell assays with very high precision.
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| 26. |
- Du, Yijun, et al.
(författare)
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Design of Sharp Roll-Off Band Notch with Fragment-Type Pattern Etched on UWB Antenna
- 2018
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Ingår i: IEEE Antennas and Wireless Propagation Letters. - 1536-1225 .- 1548-5757. ; 17:12, s. 2404-2408
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Tidskriftsartikel (refereegranskat)abstract
- Fragment-type etch patterns are proposed and designed on ultra-wideband planar antenna to acquire sharp roll-off band notch. Multi-objective evolutionary algorithm is applied to achieve the optimization searching of the best fragment-type etch pattern by setting multiple objectives to acquire the exact notched band and challenge the roll-off criterion (ROC) of band notch. Efficiency of the design can be improved by properly presetting slits on the patch radiator. For demonstration, designs with different slit presetting are implemented and tested. With single slit preset, band notch of ROC=0.72 at the WLAN band ranging from 5.15 GHz to 5.85GHz is acquired.
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| 27. |
- Faber, Zachary J, et al.
(författare)
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The genomic landscape of core-binding factor acute myeloid leukemias
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 48, s. 1551-1556
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Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes.
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| 28. |
- Fang, Du, et al.
(författare)
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Increased neuronal PreP activity reduces A beta accumulation, attenuates neuroinflammation and improves mitochondrial and synaptic function in Alzheimer disease's mouse model
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:18, s. 5198-5210
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Tidskriftsartikel (refereegranskat)abstract
- Accumulation of amyloid-beta (A beta) in synaptic mitochondria is associated with mitochondrial and synaptic injury. The underlying mechanisms and strategies to eliminate A beta and rescue mitochondrial and synaptic defects remain elusive. Presequence protease (PreP), a mitochondrial peptidasome, is a novel mitochondrial A beta degrading enzyme. Here, we demonstrate for the first time that increased expression of active human PreP in cortical neurons attenuates Alzheimer disease's (AD)-like mitochondrial amyloid pathology and synaptic mitochondrial dysfunction, and suppresses mitochondrial oxidative stress. Notably, PreP-overexpressed AD mice show significant reduction in the production of proinflammatory mediators. Accordingly, increased neuronal PreP expression improves learning and memory and synaptic function in vivo AD mice, and alleviates A beta-mediated reduction of long-term potentiation (LTP). Our results provide in vivo evidence that PreP may play an important role in maintaining mitochondrial integrity and function by clearance and degradation of mitochondrial A beta along with the improvement in synaptic and behavioral function in AD mouse model. Thus, enhancing PreP activity/expression may be a new therapeutic avenue for treatment of AD.
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| 29. |
- Gong, Wenwen, et al.
(författare)
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Emission factors of unintentional HCB and PeCBz and their correlation with PCDD/PCDF
- 2017
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Ingår i: Environmental Pollution. - : Elsevier. - 0269-7491 .- 1873-6424. ; 230, s. 516-522
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Tidskriftsartikel (refereegranskat)abstract
- Hexachlorobenzene (HCB) and pentachlorobenzene (PeCBz) have been listed as unintentional POPs in the annex of the Stockholm Convention and thus, attracted attention by government and researchers. Since the intentional production and use has ceased in most countries, the unintentional releases to the environment have increased. This study gathered 206 and 78 emission factors (EFs) of unintentional HCB and PeCBz from scientific publications and governmental reports, respectively. Most of the EFs referred to the release vector "air" (EFAir) and to a less extent to "product" (EFProduct). EFs were proposed for different source categories/classes used in the Toolkit according to the technologies that released the HCB or PeCBz. Overall, lowest and highest EFAir for HCB were found in the metallurgical industry range from 1 μg/t in well controlled plants (coke, iron and steel) up to 40,000 μg/t (secondary zinc). EFs for PeCBz were in similar order of magnitude. Due to lack of data, EFs to water, land or residue cannot be proposed. Using linear regression and statistical analysis such as Pearson correlation, we found strongest correlation of EFAir between HCB and PeCBz (R(2) = 0.79, P < 0.01) and weaker, but still significant, correlations for EFAir between PCDD/PCDFTEQ and HCB (R(2) = 0.56; P < 0.01) or PeCBz (R(2) = 0.31 P < 0.01) for various thermal processes.
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| 30. |
- Gong, Wenwen, et al.
(författare)
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Reassessment and update of emission factors for unintentional dioxin-like polychlorinated biphenyls
- 2017
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 605, s. 498-506
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Tidskriftsartikel (refereegranskat)abstract
- One of the major goals of the Stockholm Convention on Persistent Organic Pollutants is to continuously reduce the releases of unintentional persistent organic pollutants (POPs) such as polychlorinated dibenzo-paradioxins and dibenzofurans (PCDD/PCDF) or polychlorinated biphenyls (PCB) from anthropogenic sources. Until now, most efforts have focused on the releases of PCDD/PCDF and to a lesser extent on unintentionally generated PCB, and therefore, release inventories reported as toxic equivalents (TEQ) do not include the twelve dioxin-like PCB (dl-PCB). In order to facilitate the development of national release inventories for the total TEQ - consisting of PCDD, PCDF and PCB - this study collected and summarized published emission factors (EFs) of unintentional dl-PCB or calculated them from measured data for the sources listed in the UNEP Toolkit. In total, 286 EFs for dl-PCB were found (or could be calculated) whereby 233 described release to air, 23 EFs addressed to residue, 25 EFs to product; and only 5 EFs addressed releases to land. Taking into account performance criteria such as the facility type and scale or abatement technologies, the EFs were grouped and assigned to the source categories and/or classes used in the UNEP Toolkit. With these newly added data and EFs of dl-PCB, the already existing EFs in the Toolkit can be improved and amended. In addition, a statistically significant correlation between the EFAir of dl-PCB proposed in this study and EFAir of PCDD/PCDF recommended in the Toolkit was observed.
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