| 11. |
- Asami, Jinta, et al.
(författare)
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Structural basis of hepatitis B virus receptor binding
- 2024
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Ingår i: Nature Structural & Molecular Biology. - 1545-9993 .- 1545-9985. ; 31, s. 447-454
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis B virus (HBV), a leading cause of developing hepatocellular carcinoma affecting more than 290 million people worldwide, is an enveloped DNA virus specifically infecting hepatocytes. Myristoylated preS1 domain of the HBV large surface protein binds to the host receptor sodium-taurocholate cotransporting polypeptide (NTCP), a hepatocellular bile acid transporter, to initiate viral entry. Here, we report the cryogenic-electron microscopy structure of the myristoylated preS1 (residues 2–48) peptide bound to human NTCP. The unexpectedly folded N-terminal half of the peptide embeds deeply into the outward-facing tunnel of NTCP, whereas the C-terminal half formed extensive contacts on the extracellular surface. Our findings reveal an unprecedented induced-fit mechanism for establishing high-affinity virus–host attachment and provide a blueprint for the rational design of anti-HBV drugs targeting virus entry.
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| 12. |
- Choi, Nuri, et al.
(författare)
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Influence of Manufacturing Conditions on Inclusion Characteristics and Mechanical Properties of FeCrNiMnCo Alloy
- 2020
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Ingår i: Metals. - : MDPI. - 2075-4701. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Three CoCrFeMnNi high-entropy alloys (HEAs) were produced by vacuum induction melting, induction melting under inert gas atmosphere, and melting under inert gas atmosphere followed by air exposure, respectively. The different manufacturing conditions for the three investigated alloys resulted in different levels and types of inclusions. The alloys melted under vacuum or inert gas contained Al2O3 inclusions formed by impurity Al, due to its high oxidation tendency. The molten alloy exposed in air showed an excessive oxidation. During oxidation of the molten alloy in air, impurity Al was initially oxidized, and fine MnCr2O4 inclusions were formed rather than pure Al2O3 inclusions. This difference was analyzed based on thermodynamic calculations. Specifically, the influence of impurity content on the inclusion characteristics was investigated for the three HEAs. Moreover, the inclusion characteristics were found to have an influence on mechanical properties of the alloys also. In air-exposed HEA, smaller inclusions were formed, resulting in a higher dislocation density at the matrix/inclusion interface and thus strengthening of the HEA. Thus, it is proposed that atmospheric conditions could be an important factor to control the inclusion characteristics and to form fine inclusion particles, which could improve the mechanical properties of HEAs.
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| 13. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 14. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 15. |
- Kim, Bokyeong, et al.
(författare)
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Decoupled Address Translation for Heterogeneous Memory Systems
- 2020
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Ingår i: PACT '20. - New York, NY, USA : ASSOC COMPUTING MACHINERY. - 9781450380751 ; , s. 155-156
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Konferensbidrag (refereegranskat)abstract
- The support for the heterogeneous memory in the conventional virtual memory has an inherent problem. For the efficient translation in the critical translation lookaside buffers (TLBs), the page size has been growing. However, the heterogeneous memory management requires a nimble fine-grained migration mechanism to quickly move necessary memory portions to the precious fast memory. To address the challenges posed by the conflicting goals in the heterogeneous memory support, this paper proposes to decouple the address translation into a two-step process. The decoupling resolves the conflict as the critical core-side TLBs perform the translation to an intermediate address space, and the memory-side translation provides the actual physical location of the memory devices.
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| 16. |
- Kim, Bokyeong, et al.
(författare)
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Supporting Dynamic Translation Granularity for Hybrid Memory Systems
- 2022
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Ingår i: 2022 IEEE 40th International Conference on Computer Design (ICCD). - : Institute of Electrical and Electronics Engineers (IEEE). - 9781665461863 - 9781665461870 ; , s. 25-32
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Konferensbidrag (refereegranskat)abstract
- Hybrid memory has become a promising new solution for meeting ever growing memory capacity demands in a cost-effective way. In hybrid memory systems, the fast and high bandwidth memory is used to store performance-critical data, while the slow and low bandwidth memory provides capacity backup. In supporting such hybridization, virtual memory is the key mechanism, which can combine different memory components to a single memory view. For efficient translation for virtual memory, page size has been growing. However, the hybrid memory support requires fine-grained migration to quickly move only necessary memory portions to the precious fast memory. To address the challenges posed by the conflicting goals in the hybrid memory support based on virtual memory, this paper investigates decoupling of address translation into a two-step process. With the two-level translation, the critical core-side TLBs perform the translation to an intermediate address space, and the memory-side translation provides the actual physical location in memory devices. As the second-level translation handling page migration across different memory types, is decoupled from the first-level translation, it allows dynamic adjustment of its mapping granularity to improve the efficiency of translation and data reuse in the fast memory. This paper proposes a hardware architecture which identifies the memory access behavior of an application online and selects the best mapping granularity for the second-level translation.
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| 17. |
- Kim, D. H., et al.
(författare)
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Improving the production efficiency of high-titania slag in Ti extraction process : fluxing effect on formation of pseudobrookite
- 2020
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Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the carbothermic reduction process of ilmenite ore at 1873 K with flux addition. Without flux, the pseudobrookite phase with a high melting temperature was precipitated during ilmenite smelting. This could be the main reason for decreased reduction of iron in ilmenite. To accelerate reduction of ilmenite, two factors were considered. One is increasing the reduction driving force during smelting. Activity of FeO is the major factor to control reduction in driving force. The other factor is delay in formation of the pseudobrookite phase, a high-melting point precipitation phase. In this system, MgO in ilmenite could be used to form pseudobrookite. To control these factors, in this study, flux agent (i.e., Na2O or SiO2) addition was considered. The thermochemical simulation program, FactSageTM7.0 was used to calculate the viscosity of slag and the activity of components as fluxing agents were added. High-temperature experiments using an induction furnace were also conducted to confirm the computational results. To determine the composition of final products, i.e., titanium slag, X-ray fluorescence analysis was executed. As a result of Fe and Ti behaviours in slag, SiO2 addition showed no significant difference from the slag without flux. However, Fe reduction in ilmenite, i.e. TiO2-enrichment, was more accelerated when Na2O was added. X-ray diffraction, scanning electron microscopic and transmission electron microscopic analyses results also showed that even 1 wt% Na2O addition significantly influenced the titanium slag production compared to no flux addition.
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| 18. |
- 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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| 19. |
- Koo, Jun Mo, et al.
(författare)
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Nonstop Monomer-to-Aramid Nanofiber Synthesis with Remarkable Reinforcement Ability
- 2019
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Ingår i: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 52:3, s. 923-934
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Tidskriftsartikel (refereegranskat)abstract
- Aramid nanofibers (ANFs), typically produced by exfoliating aramid microfibers (Kevlar) in alkaline media, exhibit excellent mechanical properties and have therefore attracted increased attention as nanoscale building blocks. However, the preparation of aramid microfibers involves laborious and hazardous processes, which limits the industrial-scale use of ANFs. This work describes a facile and direct monomer-to-ANF synthesis via an as-synthesized intermediate low-molecular-weight poly(p-phenylene terephthalamide) (PPTA) without requiring the environmentally destructive acids and high-order shearing processes. Under the employed conditions, PPTA immediately dissociates and self-assembles into ANFs within a time period of 15 h, which is much shorter than the time of 180 h (not including the Kevlar preparation time) required for the Kevlar-to-ANF conversion. Interestingly, the fabricated ANFs exhibit nanoscale dimensions and thermoplastic polyurethane (TPU) reinforcing effects similar to those of Kevlar-derived ANFs; i.e., a 1.5-fold TPU toughness improvement and a maximum ultimate tensile strength of 84 MPa are achieved at an ANF content of only 0.04 wt %. Remarkable reinforcement ability investigated by comprehensive analytical data comes from ANFs, which disturb ordered hydrogen bonding in hard segments and induce strain hardening along the elongation pathway. Thus, the developed approach paves the way to industrial-scale production of ANFs and related nanocomposites.
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| 20. |
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