| 1. |
- Allen-Philbey, Kimberley, et al.
(författare)
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Subcutaneous cladribine to treat multiple sclerosis : experience in 208 patients
- 2021
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Ingår i: Therapeutic Advances in Neurological Disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients. Methods: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3–4 days during week 1. Based on lymphocyte count at week 4, patients received another 0–3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. Results: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17–72) years and EDSS 0–8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data (n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data (n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. Conclusions: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.
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| 2. |
- Baker, Maggie, et al.
(författare)
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Early rearing history influences oxytocin receptor epigenetic regulation in rhesus macaques
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 114:44, s. 11769-11774
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Tidskriftsartikel (refereegranskat)abstract
- Adaptations to stress can occur through epigenetic processes and may be a conduit for informing offspring of environmental challenge. We employed ChIP-sequencing for H3K4me3 to examine effects of early maternal deprivation (peer-rearing, PR) in archived rhesus macaque hippocampal samples (male, n = 13). Focusing on genes with roles in stress response and behavior, we assessed the effects of rearing on H3K4me3 binding by ANOVA. We found decreased H3K4me3 binding at genes critical to behavioral stress response, the most robust being the oxytocin receptor gene OXTR, for which we observed a corresponding decrease in RNA expression. Based on this finding, we performed behavioral analyses to deter mine whether a gain-of-function nonsynonymous OXTR SNP inter acted with early stress to influence relevant behavioral stress reactivity phenotypes (n = 194), revealing that this SNP partially rescued the PR phenotype. PR infants exhibited higher levels of separation anxiety and arousal in response to social separation, but infants carrying the alternative OXTR allele did not exhibit as great a separation response. These data indicate that the oxytocin system is involved in social-separation response and suggest that epigenetic down-modulation of OXTR could contribute to behavior al differences observed in PR animals. Epigenetic changes at OXTR may represent predictive adaptive responses that could impart readiness to respond to environmental challenge or maintain proximity to a caregiver but also contribute to behavioral pathology. Our data also demonstrate that OXTR polymorphism can permit animals to partially overcome the detrimental effects of early maternal deprivation, which could have translational implications for human psychiatric disorders.
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| 3. |
- Barbier, Estelle, et al.
(författare)
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DNA Methylation in the Medial Prefrontal Cortex Regulates Alcohol-Induced Behavior and Plasticity
- 2015
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 35:15, s. 6153-6164
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have suggested an association between alcoholism and DNA methylation, a mechanism that can mediate long-lasting changes in gene transcription. Here, we examined the contribution of DNA methylation to the long-term behavioral and molecular changes induced by a history of alcohol dependence. In search of mechanisms underlying persistent rather than acute dependence-induced neuroadaptations, we studied the role of DNA methylation regulating medial prefrontal cortex (mPFC) gene expression and alcohol-related behaviors in rats 3 weeks into abstinence following alcohol dependence. Postdependent rats showed escalated alcohol intake, which was associated with increased DNA methylation as well as decreased expression of genes encoding synaptic proteins involved in neurotransmitter release in the mPFC. Infusion of the DNA methyltransferase inhibitor RG108 prevented both escalation of alcohol consumption and dependence-induced downregulation of 4 of the 7 transcripts modified in postdependent rats. Specifically, RG108 treatment directly reversed both downregulation of synaptotagmin 2 (Syt2) gene expression and hypermethylation on CpG#5 of its first exon. Lentiviral inhibition of Syt2 expression in the mPFC increased aversion-resistant alcohol drinking, supporting a mechanistic role of Syt2 in compulsive-like behavior. Our findings identified a functional role of DNA methylation in alcohol dependence-like behavioral phenotypes and a candidate gene network that may mediate its effects. Together, these data provide novel evidence for DNA methyltransferases as potential therapeutic targets in alcoholism.
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| 4. |
- Chen, Yujie, et al.
(författare)
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Unraveling dual phase transformations in a CrCoNi medium-entropy alloy
- 2021
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Ingår i: Acta Materialia. - : Elsevier BV. - 1359-6454 .- 1873-2453. ; 215
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Tidskriftsartikel (refereegranskat)abstract
- The emergence of multi-principal element alloys (MPEAs) holds great promise for the development of high performance metallic materials. However, it remains unclear whether MPEAs can provide previously unknown deformation mechanisms to drastically enhance their mechanical performance. Here we report a new deformation mechanism of mechanically-induced dual phase transformations from the face-centered cubic (FCC) to hexagonal close- packed (HCP) phase and then back to the FCC phase with nanotwins in a CrCoNi medium-entropy alloy (MEA). During the two sequential steps of phase transformation, continued shear occurs in the same < 110 >(FCC) parallel to < 11 (2) over bar0 >(HCP) direction along different {111}(FCC) parallel to (0001)(HCP) planes, producing a total shear transformation strain up to 70%. The dual phase transformations stem from a unique capability of facile slip in between the close-packed {111}(FCC) parallel to (0001)(HCP) atomic layers in both FCC and HCP phases, leading to flexible stacking sequences of those close-packed layers with low stacking fault energies. Our work demonstrates that MPEAs can offer unconventional deformation mechanisms such as dual phase transformations in the CrCoNi MEA, thereby opening opportunities for enhancing the mechanical properties of advanced alloys.
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| 5. |
- Huang, Zhifeng, et al.
(författare)
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Three-dimensional posture optimization for biped robot stepping over large ditch based on a ducted-fan propulsion system
- 2020
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Ingår i: IEEE International Conference on Intelligent Robots and Systems. - 2153-0858 .- 2153-0866. ; , s. 3591-3597
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Konferensbidrag (refereegranskat)abstract
- The recent progress of an ongoing project utilizing a ducted-fan propulsion system to improve a humanoid robot's ability to step over large ditches is reported. A novel method (GAS) based on the genetic algorithm with smoothness constraint can effectively minimize the thrust by optimizing the robot's posture during 3D stepping. The significant advantage of the method is that it can realize the continuity and smoothness of the thrust and pelvis trajectories. The method enables the landing point of the robot's swing foot to be not only in the forward but also in a side direction. The methods were evaluated by simulation and by being applied on a prototype robot, JetHR1. By keeping a quasistatic balance, the robot could step over a ditch with a span of 450 mm (as much as 97% of the length of the robot's leg) in 3D stepping.
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| 6. |
- Lederman, Judith, et al.
(författare)
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An international collaborative investigation of beginning seventh grade students' understandings of scientific inquiry : Establishing a baseline
- 2019
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Ingår i: Journal of Research in Science Teaching. - : Wiley. - 0022-4308 .- 1098-2736. ; 56:4, s. 486-515
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Tidskriftsartikel (refereegranskat)abstract
- Although understandings of scientific inquiry (as opposed to conducting inquiry) are included in science education reform documents around the world, little is known about what students have learned about inquiry during their elementary school years. This is partially due to the lack of any assessment instrument to measure understandings about scientific inquiry. However, a valid and reliable assessment has recently been developed and published, Views About Scientific Inquiry (VASI; Lederman et al. [2014], Journal of Research in Science Teaching, 51, 65-83). The purpose of this large-scale international project was to collect the first baseline data on what beginning middle school students have learned about scientific inquiry during their elementary school years. Eighteen countries/regions spanning six continents including 2,634 students participated in the study. The participating countries/regions were: Australia, Brazil, Chile, Egypt, England, Finland, France, Germany, Israel, Mainland China, New Zealand, Nigeria, South Africa, Spain, Sweden, Taiwan, Turkey, and the United States. In many countries, science is not formally taught until middle school, which is the rationale for choosing seventh grade students for this investigation. This baseline data will simultaneously provide information on what, if anything, students learn about inquiry in elementary school, as well as their beginning knowledge as they enter secondary school. It is important to note that collecting data from all of the approximately 200 countries globally was not humanly possible, and it was also not possible to collect data from every region of each country. The results overwhelmingly show that students around the world at the beginning of grade seven have very little understandings about scientific inquiry. Some countries do show reasonable understandings in certain aspects but the overall picture of understandings of scientific inquiry is not what is hoped for after completing 6 years of elementary education in any country.
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| 7. |
- Sun, Lian, et al.
(författare)
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Exploring the influence of reservoir impoundment on surrounding tree growth
- 2021
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Ingår i: Advances in Water Resources. - : Elsevier BV. - 0309-1708 .- 1872-9657. ; 153
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Tidskriftsartikel (refereegranskat)abstract
- At the local scale, artificial impounded reservoirs in dry regions exert influence on the surrounding local climate. Impounded reservoirs have been found to alter precipitation patterns and increase temperature, specific humidity and surface evaporation. The consequences of impoundment or its related climatic changes on the surrounding vegetation are still not well understood. We here examined the potential effect on surrounding tree growth of the impoundment of the Ertan Reservoir, China, in 1998. We measured Yunnan pine tree rings at three sites on a slope close to the reservoir and two control sites far away from the reservoir. We compared the annual radial growth of tree rings at all sites with air temperature, precipitation and air humidity in the region. We also used cumulative distribution functions to quantify the probability of attributing radial growth changes to background climate variability. We find an enhancement of tree growth from 2000 to 2002, right after the reservoir's impounding in experimental and control sites. Hence, the tree growth can initially be explained by favourable conditions benefiting tree growth. However, we cannot entirely attribute such enhancement to the background climate variability when studying the relationship between tree growth and climatic variables over the 36 years and their probability of occurrence. Tree growth in the three years following impoundment can only be attributed to the simultaneous effect of favourable regional climate conditions and the reservoir's impoundment in itself. These conditions decrease vegetation stress by decreasing air temperature and increasing air relative humidity. Although the findings of this study shed more light on the environmental and climatic changes induced by the impoundment of reservoirs, they also call for the need of monitoring climatic variables in the vicinity of reservoirs.
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| 8. |
- Zhang, Jibin, et al.
(författare)
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A Multifunctional "Halide-Equivalent" Anion Enabling Efficient CsPb(Br/I)(3) Nanocrystals Pure-Red Light-Emitting Diodes with External Quantum Efficiency Exceeding 23%
- 2023
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Ingår i: Advanced Materials. - : WILEY-V C H VERLAG GMBH. - 0935-9648 .- 1521-4095. ; 35:8
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Tidskriftsartikel (refereegranskat)abstract
- Pure-red perovskite LEDs (PeLEDs) based on CsPb(Br/I)(3) nanocrystals (NCs) usually suffer from a compromise in emission efficiency and spectral stability on account of the surface halide vacancies-induced nonradiative recombination loss, halide phase segregation, and self-doping effect. Herein, a "halide-equivalent" anion of benzenesulfonate (BS-) is introduced into CsPb(Br/I)(3) NCs as multifunctional additive to simultaneously address the above challenging issues. Joint experiment-theory characterizations reveal that the BS- can not only passivate the uncoordinated Pb2+-related defects at the surface of NCs, but also increase the formation energy of halide vacancies. Moreover, because of the strong electron-withdrawing property of sulfonate group, electrons are expected to transfer from the CsPb(Br/I)(3) NC to BS- for reducing the self-doping effect and altering the n-type behavior of CsPb(Br/I)(3) NCs to near ambipolarity. Eventually, synergistic boost in device performance is achieved for pure-red PeLEDs with CIE coordinates of (0.70, 0.30) and a champion external quantum efficiency of 23.5%, which is one of the best value among the ever-reported red PeLEDs approaching to the Rec. 2020 red primary color. Moreover, the BS--modified PeLED exhibits negligible wavelength shift under different operating voltages. This strategy paves an efficient way for improving the efficiency and stability of pure-red PeLEDs.
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| 9. |
- Zhang, Jibin, et al.
(författare)
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Ligand-Induced Cation-p Interactions Enable High-Efficiency, Bright, and Spectrally Stable Rec. 2020 Pure-Red Perovskite Light-Emitting Diodes
- 2023
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Ingår i: Advanced Materials. - : WILEY-V C H VERLAG GMBH. - 0935-9648 .- 1521-4095.
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Tidskriftsartikel (refereegranskat)abstract
- Achieving high-performance perovskite light-emitting diodes (PeLEDs) with pure-red electroluminescence for practical applications remains a critical challenge because of the problematic luminescence property and spectral instability of existing emitters. Herein, high-efficiency Rec. 2020 pure-red PeLEDs, simultaneously exhibiting exceptional brightness and spectral stability, based on CsPb(Br/I)(3) perovskite nanocrystals (NCs) capping with aromatic amino acid ligands featuring cation-pi interactions, are reported. It is proven that strong cation-pi interactions between the PbI6-octahedra of perovskite units and the electron-rich indole ring of tryptophan (TRP) molecules not only chemically polish the imperfect surface sites, but also markedly increase the binding affinity of the ligand molecules, leading to high photoluminescence quantum yields and greatly enhanced spectral stability of the CsPb(Br/I)(3) NCs. Moreover, the incorporation of small-size aromatic TRP ligands ensures superior charge-transport properties of the assembled emissive layers. The resultant devices emitting at around 635 nm demonstrate a champion external quantum efficiency of 22.8%, a max luminance of 12 910 cd m(-2), and outstanding spectral stability, representing one of the best-performing Rec. 2020 pure-red PeLEDs achieved so far.
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