1,104 research outputs found
Depth-Resolved Composition and Electronic Structure of Buried Layers and Interfaces in a LaNiO/SrTiO Superlattice from Soft- and Hard- X-ray Standing-Wave Angle-Resolved Photoemission
LaNiO (LNO) is an intriguing member of the rare-earth nickelates in
exhibiting a metal-insulator transition for a critical film thickness of about
4 unit cells [Son et al., Appl. Phys. Lett. 96, 062114 (2010)]; however, such
thin films also show a transition to a metallic state in superlattices with
SrTiO (STO) [Son et al., Appl. Phys. Lett. 97, 202109 (2010)]. In order to
better understand this transition, we have studied a strained LNO/STO
superlattice with 10 repeats of [4 unit-cell LNO/3 unit-cell STO] grown on an
(LaAlO)(SrAlTaO) substrate using soft x-ray
standing-wave-excited angle-resolved photoemission (SWARPES), together with
soft- and hard- x-ray photoemission measurements of core levels and
densities-of-states valence spectra. The experimental results are compared with
state-of-the-art density functional theory (DFT) calculations of band
structures and densities of states. Using core-level rocking curves and x-ray
optical modeling to assess the position of the standing wave, SWARPES
measurements are carried out for various incidence angles and used to determine
interface-specific changes in momentum-resolved electronic structure. We
further show that the momentum-resolved behavior of the Ni 3d eg and t2g states
near the Fermi level, as well as those at the bottom of the valence bands, is
very similar to recently published SWARPES results for a related
LaSrMnO/SrTiO superlattice that was studied using the
same technique (Gray et al., Europhysics Letters 104, 17004 (2013)), which
further validates this experimental approach and our conclusions. Our
conclusions are also supported in several ways by comparison to DFT
calculations for the parent materials and the superlattice, including
layer-resolved density-of-states results
The Influence of Gestational Diabetes on Neurodevelopment of Children in the First Two Years of Life: A Prospective Study
10.1371/journal.pone.0162113PloS one119e0162113GUSTO (Growing up towards Healthy Outcomes
Solar thermal hybrids for combustion power plant: A growing opportunity
The development of technologies to hybridise concentrating solar thermal energy (CST) and combustion technologies, is driven by the potential to provide both cost-effective CO2 mitigation and firm supply. Hybridisation, which involves combining the two energy sources within a single plant, offers these benefits over the stand-alone counterparts through the use of shared infrastructure and increased efficiency. In the near-term, hybrids between solar and fossil fuelled systems without carbon capture offer potential to lower the use of fossil fuels, while in the longer term they offer potential for low-cost carbon-neutral or carbon-negative energy. The integration of CST into CO2 capture technologies such as oxy-fuel combustion and chemical looping combustion is potentially attractive because the same components can be used for both CO2 capture and the storage of solar energy, to reduce total infrastructure and cost. The use of these hybrids with biomass and/or renewable fuels, offers the additional potential for carbon-negative energy with relatively low cost. In addition to reviewing these technologies, we propose a methodology for classifying solar-combustion hybrid technologies and assess the progress and challenges of each. Particular attention is paid to "direct hybrids", which harness the two energy sources in a common solar receiver or reactor to reduce total infrastructure and losses.G.J.Nathan, M.Jafarian, B.B.Dally, W.L.Saw, P.J.Ashman, E.Hu, A.Steinfel
Maternal Dietary Patterns and Gestational Diabetes Mellitus in a Multi-Ethnic Asian Cohort: The GUSTO Study
10.3390/nu8090574Nutrients89article no. 574GUSTO (Growing up towards Healthy Outcomes
A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling.
Mechanisms that integrate the metabolic state of a cell with regulatory pathways are necessary to maintain cellular homeostasis. Endogenous, intrinsically reactive metabolites can form functional, covalent modifications on proteins without the aid of enzymes1,2, and regulate cellular functions such as metabolism3-5 and transcription6. An important 'sensor' protein that captures specific metabolic information and transforms it into an appropriate response is KEAP1, which contains reactive cysteine residues that collectively act as an electrophile sensor tuned to respond to reactive species resulting from endogenous and xenobiotic molecules. Covalent modification of KEAP1 results in reduced ubiquitination and the accumulation of NRF27,8, which then initiates the transcription of cytoprotective genes at antioxidant-response element loci. Here we identify a small-molecule inhibitor of the glycolytic enzyme PGK1, and reveal a direct link between glycolysis and NRF2 signalling. Inhibition of PGK1 results in accumulation of the reactive metabolite methylglyoxal, which selectively modifies KEAP1 to form a methylimidazole crosslink between proximal cysteine and arginine residues (MICA). This posttranslational modification results in the dimerization of KEAP1, the accumulation of NRF2 and activation of the NRF2 transcriptional program. These results demonstrate the existence of direct inter-pathway communication between glycolysis and the KEAP1-NRF2 transcriptional axis, provide insight into the metabolic regulation of the cellular stress response, and suggest a therapeutic strategy for controlling the cytoprotective antioxidant response in several human diseases
Dense active matter model of motion patterns in confluent cell monolayers
Epithelial cell monolayers show remarkable displacement and velocity
correlations over distances of ten or more cell sizes that are reminiscent of
supercooled liquids and active nematics. We show that many observed features
can be described within the framework of dense active matter, and argue that
persistent uncoordinated cell motility coupled to the collective elastic modes
of the cell sheet is sufficient to produce swirl-like correlations. We obtain
this result using both continuum active linear elasticity and a normal modes
formalism, and validate analytical predictions with numerical simulations of
two agent-based cell models, soft elastic particles and the self-propelled
Voronoi model together with in-vitro experiments of confluent corneal
epithelial cell sheets. Simulations and normal mode analysis perfectly match
when tissue-level reorganisation occurs on times longer than the persistence
time of cell motility. Our analytical model quantitatively matches measured
velocity correlation functions over more than a decade with a single fitting
parameter.Comment: updated version accepted for publication in Nat. Com
Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells
Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins
Predictors of allergen sensitization in Singapore children from birth to 3 years
10.1186/s13223-016-0161-xAllergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology121Article number 56GUSTO (Growing up towards Healthy Outcomes
Protein crystals in adenovirus type 5-infected cells: requirements for intranuclear crystallogenesis, structural and functional analysis
Intranuclear crystalline inclusions have been observed in the nucleus of epithelial cells infected with Adenovirus serotype 5 (Ad5) at late steps of the virus life cycle. Using immuno-electron microscopy and confocal microscopy of cells infected with various Ad5 recombinants modified in their penton base or fiber domains, we found that these inclusions represented crystals of penton capsomers, the heteromeric capsid protein formed of penton base and fiber subunits. The occurrence of protein crystals within the nucleus of infected cells required the integrity of the fiber knob and part of the shaft domain. In the knob domain, the region overlapping residues 489–492 in the FG loop was found to be essential for crystal formation. In the shaft, a large deletion of repeats 4 to 16 had no detrimental effect on crystal inclusions, whereas deletion of repeats 8 to 21 abolished crystal formation without altering the level of fiber protein expression. This suggested a crucial role of the five penultimate repeats in the crystallisation process. Chimeric pentons made of Ad5 penton base and fiber domains from different serotypes were analyzed with respect to crystal formation. No crystal was found when fiber consisted of shaft (S) from Ad5 and knob (K) from Ad3 (heterotypic S5-K3 fiber), but occurred with homotypic S3K3 fiber. However, less regular crystals were observed with homotypic S35-K35 fiber. TB5, a monoclonal antibody directed against the Ad5 fiber knob was found by immunofluorescence microscopy to react with high efficiency with the intranuclear protein crystals in situ. Data obtained with Ad fiber mutants indicated that the absence of crystalline inclusions correlated with a lower infectivity and/or lower yields of virus progeny, suggesting that the protein crystals might be involved in virion assembly. Thus, we propose that TB5 staining of Ad-infected 293 cells can be used as a prognostic assay for the viability and productivity of fiber-modified Ad5 vectors
Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists
Aims Oral anticoagulation with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) is effective but has significant limitations. AZD0837, a new oral anticoagulant, is a prodrug converted to a selective and reversible direct thrombin inhibitor (AR-H067637). We report from a Phase II randomized, dose-guiding study (NCT00684307) to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of extended-release AZD0837 in patients with AF. Methods and results Atrial fibrillation patients (n = 955) with >= 1 additional risk factor for stroke were randomized to receive AZD0837 (150, 300, or 450 mg once daily or 200 mg twice daily) or VKA (international normalized ratio 2-3, target 2.5) for 3-9 months. Approximately 30% of patients were naive to VKA treatment. Total bleeding events were similar or lower in all AZD0837 groups (5.3-14.7%, mean exposure 138-145 days) vs. VKA (14.5%, mean exposure 161 days), with fewer clinically relevant bleeding events on AZD0837 150 and 300 mg once daily. Adverse events were similar between treatment groups; with AZD0837, the most common were gastrointestinal disorders (e.g. diarrhoea, flatulence, or nausea). D-Dimer, used as a biomarker of thrombogenesis, decreased in all groups in VKA-naive subjects with treatment, whereas in VKA pre-treated patients, D-dinner levels started tow and remained low in all groups. As expected, only a few strokes or systemic embolic events occurred. In the AZD0837 groups, mean S-creatinine increased by similar to 10% from baseline and returned to baseline following treatment cessation. The frequency of serum alanine aminotransferase >= 3 x upper limit of normal was similar for AZD0837 and VKA. Conclusion AZD0837 was generally well tolerated at all doses tested. AZD0837 treatment at an exposure corresponding to the 300 mg od dose in this study provides similar suppression of thrombogenesis at a potentially lower bleeding risk compared with dose-adjusted VKA
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