| 1. |
- Kim, Joon Tae, et al.
(författare)
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Dual antiplatelet Use for extended period taRgeted to AcuTe ischemic stroke with presumed atherosclerotic OrigiN (DURATION) trial : Rationale and design
- 2023
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 18:8, s. 1015-1020
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The optimal duration of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin for the large artery atherosclerotic (LAA) stroke subtype has been debated. Aims: To determine whether the 1-year risk of recurrent vascular events could be reduced by a longer duration of DAPT in patients with the LAA stroke subtype. Methods and study design: A total of 4806 participants will be recruited to detect a statistically significant relative risk reduction of 22% with 80% power and a two-sided alpha error of 0.05, including a 10% loss to follow-up. This is a registry-based, multicenter, prospective, randomized, open-label, blinded end point study designed to evaluate the efficacy and safety of a 12-month duration of DAPT compared with a 3-month duration of DAPT in the LAA stroke subtype. Patients will be randomized (1:1) to either DAPT for 12 months or DAPT for 3 months, followed by monotherapy (either aspirin or clopidogrel) for the remaining 9 months. Study outcomes: The primary efficacy outcome of the study is a composite of stroke (ischemic or hemorrhagic), myocardial infarction, and all-cause mortality for 1 year after the index stroke. The secondary efficacy outcomes are (1) stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, and (4) all-cause mortality. The primary safety outcome is major bleeding. Discussion: This study will help stroke physicians determine the appropriate duration of dual therapy with clopidogrel-aspirin for patients with the LAA stroke subtype. Trial registration: URL: https://cris.nih.go.kr/cris. CRIS Registration Number: KCT0004407.
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| 2. |
- Luo, Yifei, et al.
(författare)
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Technology Roadmap for Flexible Sensors
- 2023
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Ingår i: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 17:6, s. 5211-5295
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Forskningsöversikt (refereegranskat)abstract
- Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.
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| 3. |
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| 4. |
- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 5. |
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| 6. |
- Song, Byong-Sop, et al.
(författare)
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Mitoribosomal defects aggravate liver cancer via aberrant glycolytic flux and T cell exhaustion
- 2022
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Ingår i: Journal for ImmunoTherapy of Cancer. - : BMJ. - 2051-1426. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Background Mitochondria are involved in cancer energy metabolism, although the mechanisms underlying the involvement of mitoribosomal dysfunction in hepatocellular carcinoma (HCC) remain poorly understood. Here, we investigated the effects of mitoribosomal impairment-mediated alterations on the immunometabolic characteristics of liver cancer.Methods We used a mouse model of HCC, liver tissues from patients with HCC, and datasets from The Cancer Genome Atlas (TCGA) to elucidate the relationship between mitoribosomal proteins (MRPs) and HCC. In a mouse model, we selectively disrupted expression of the mitochondrial ribosomal protein CR6-interacting factor 1 (CRIF1) in hepatocytes to determine the impact of hepatocyte-specific impairment of mitoribosomal function on liver cancer progression. The metabolism and immunophenotype of liver cancer was assessed by glucose flux assays and flow cytometry, respectively.Results Single-cell RNA-seq analysis of tumor tissue and TCGA HCC transcriptome analysis identified mitochondrial defects associated with high-MRP expression and poor survival outcomes. In the mouse model, hepatocyte-specific disruption of the mitochondrial ribosomal protein CRIF1 revealed the impact of mitoribosomal dysfunction on liver cancer progression. Crif1 deficiency promoted programmed cell death protein 1 expression by immune cells in the hepatic tumor microenvironment. A [U-13C6]-glucose tracer demonstrated enhanced glucose entry into the tricarboxylic acid cycle and lactate production in mice with mitoribosomal defects during cancer progression. Mice with hepatic mitoribosomal defects also exhibited enhanced progression of liver cancer accompanied by highly exhausted tumor-infiltrating T cells. Crif1 deficiency induced an environment unfavorable to T cells, leading to exhaustion of T cells via elevation of reactive oxygen species and lactate production.Conclusions Hepatic mitoribosomal defects promote glucose partitioning toward glycolytic flux and lactate synthesis, leading to T cell exhaustion and cancer progression. Overall, the results suggest a distinct role for mitoribosomes in regulating the immunometabolic microenvironment during HCC progression.
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| 7. |
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| 8. |
- Kim, Tae Young, et al.
(författare)
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Dna polymerase alpha subunit b is a binding protein for erlotinib resistance in non-small cell lung cancer
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:9, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Erlotinib inhibits epithelial growth factor receptor (EGFR) kinase activity and is used to treat non-small cell lung cancer (NSCLC). Despite its high efficacy, recurrence can occur in patients who become resistant to the drug. To address the underlying mechanism of Erlotinib resistance, we investigated additional mechanisms related to mode-of-drug-action, by multiple protein-binding interactions, besides EGFR by using drug affinity responsive target stability (DARTS) and liquid chromatography-mass spectrometry (LC-MS/MS) methods with non-labeled Erlotinib. DNA polymerase alpha subunit B (POLA2) was identified as a new Erlotinib binding protein that was validated by the DARTS platform, complemented with cellular thermal shift assays. Genetic knock-down of POLA2 promoted the anti-proliferative effect of the drug in the Erlotinib-resistant cell line H1299 with high POLA2 expression, whereas the overexpression of POLA2 restored anti-proliferative effects in the Erlotinib-sensitive cell line HCC827 with low POLA2 expression. Importantly, POLA2 expression levels in four NSCLC cell lines were positively correlated with anti-proliferative Erlotinib efficacy (Pearson correlation coefficient, R = 0.9886). These results suggest that POLA2 is a novel complementary target protein of Erlotinib, and could clinically provide validity as a surrogate marker for drug resistance in patients with NSCLC.
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| 9. |
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| 10. |
- Kim, Yonghyo, et al.
(författare)
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Identification and validation of VEGFR2 kinase as a target of voacangine by a systematic combination of DARTS and MSI
- 2020
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Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Although natural products are an important source of drugs and drug leads, identification and validation of their target proteins have proven difficult. Here, we report the development of a systematic strategy for target identification and validation employing drug affinity responsive target stability (DARTS) and mass spectrometry imaging (MSI) without modifying or labeling natural compounds. Through a validation step using curcumin, which targets aminopeptidase N (APN), we successfully standardized the systematic strategy. Using label-free voacangine, an antiangiogenic alkaloid molecule as the model natural compound, DARTS analysis revealed vascular endothelial growth factor receptor 2 (VEGFR2) as a target protein. Voacangine inhibits VEGFR2 kinase activity and its downstream signaling by binding to the kinase domain of VEGFR2, as was revealed by docking simulation. Through cell culture assays, voacangine was found to inhibit the growth of glioblastoma cells expressing high levels of VEGFR2. Specific localization of voacangine to tumor compartments in a glioblastoma xenograft mouse was revealed by MSI analysis. The overlap of histological images with the MSI signals for voacangine was intense in the tumor regions and showed colocalization of voacangine and VEGFR2 in the tumor tissues by immunofluorescence analysis of VEGFR2. The strategy employing DARTS and MSI to identify and validate the targets of a natural compound as demonstrated for voacangine in this study is expected to streamline the general approach of drug discovery and validation using other biomolecules including natural products.
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| 11. |
- Koenig, Julian, et al.
(författare)
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Cortical thickness and resting-state cardiac function across the lifespan : A cross-sectional pooled mega-analysis
- 2021
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Ingår i: Psychophysiology. - : Wiley. - 0048-5772 .- 1469-8986 .- 1540-5958. ; 58:7
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12–87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS—or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
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| 12. |
- Lee, Da Hye, et al.
(författare)
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Phase formation behavior and hydrogen sorption characteristics of TiFe0.8Mn0.2 powders prepared by gas atomization
- 2023
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Ingår i: International journal of hydrogen energy. - : Elsevier BV. - 0360-3199 .- 1879-3487. ; 48:71, s. 27697-27709
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Tidskriftsartikel (refereegranskat)abstract
- In this article we have investigated the phase formation behavior and hydrogen storage characteristics of TiFe0.8Mn0.2 samples produced by electrode induction melting gas at-omization (EIGA) as well as conventional vacuum arc-melting (VAM). TiFe (46Ti-46Fe-8Mn (wt%) with cubic, CsCl-type structure) and C14 Laves (37Ti-51Fe-12Mn (wt%) with hex-agonal, MgZn2-type structure) phases were detected in both atomized powders and crushed ingots, the latter possessing a lower fraction of Laves phase. Microstructural characterization included electron probe micro-analysis (EPMA) and transmission electron microscopy (TEM), which evidenced the existence of a non-equilibrium Ti2Fe phase in the atomized powders. The formation of this additional secondary phase was attributed to the rapid cooling rate during powder manufacturing, based on earlier findings and phase formation thermodynamic calculations combined with Scheil solidification simulations. In addition, kinetics and pressure-composition isotherms (PCIs) were acquired to determine both absorption and desorption enthalpy/entropy, as well as to study the influence of the synthesis route (and hence the resulting microstructure) on kinetics, thermodynamics and reaction mechanisms of the TiFe0.8Mn0.2 alloy. & COPY; 2023 Hydrogen Energy Publications LLC. Published by Elsevier Ltd. All rights reserved.
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