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The aquamarine discharge exemplifies polymerization of acetylene in a DBD reactor. In total, over 20 precursors were classified for their “ease” of film deposition and growth at low energy ...input. Next to acetylene, pyrrole is the precursor of choice. In‐depth analysis of the polymer films offers insights in their physicochemical properties. The research was a combined effort of VITO and KULeuven. Further details can be found in the article by P. Heyse, R. Dams, S. Paulussen,
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K. Houthoofd, K. Janssen, P. A. Jacobs, and B. F. Sels on page 145.
Machine Learning and LHC Event Generation Butter, Anja; Plehn, Tilman; Schumann, Steffen ...
OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information),
12/2022
Paper, Journal Article
Odprti dostop
First-principle simulations are at the heart of the high-energy physics research program. They link the vast data output of multi-purpose detectors with fundamental theory predictions and ...interpretation. This review illustrates a wide range of applications of modern machine learning to event generation and simulation-based inference, including conceptional developments driven by the specific requirements of particle physics. New ideas and tools developed at the interface of particle physics and machine learning will improve the speed and precision of forward simulations, handle the complexity of collision data, and enhance inference as an inverse simulation problem.
In rat mesangial cells, exogenously added secreted phospholipases
A 2 (sPLA 2 s) potentiate the expression of
pro-inflammatory sPLA 2 -IIA first induced by cytokines like tumor
necrosis factor-α ...(TNFα) and interleukin-1β. The
transcriptional pathway mediating this effect is, however, unknown. Because
products of PLA 2 activity are endogenous activators of peroxisome
proliferator-activated receptor α (PPARα, we postulated that
sPLA 2 s mediate their effects on sPLA 2 -IIA expression via
sPLA 2 activity and subsequent PPARα activation. This study
shows that various sPLA 2 s, including venom enzymes, human
sPLA 2 -IIA, and wild-type and catalytically inactive H48Q mutant of
porcine pancreatic sPLA 2 -IB, enhance the TNFα-induced
sPLA 2 -IIA expression at the mRNA and protein levels. In cells
transfected with luciferase sPLA 2 -IIA promoter constructs,
sPLA 2 s are active only when the promoter contains a functional
PPRE-1 site. The effect of exogenous sPLA 2 s is also blocked by the
PPARα inhibitor MK886. Interestingly, the expression of
sPLA 2 -IIA induced by TNFα alone is also attenuated by MK886,
by the sPLA 2 -IIA inhibitor LY311727, by heparinase, which prevents
the binding of sPLA 2 -IIA to heparan sulfate proteoglycans, and by
the specific cPLA 2 -α inhibitor pyrrolidine-1. Together, these
data indicate that sPLA 2 -IIA released from mesangial cells by
TNFα stimulates its own expression via an autocrine loop involving
cPLA 2 and PPARα. This signaling pathway is also used by
exogenously added sPLA 2 s including pancreatic sPLA 2 -IB
and is distinct from that used by TNFα.
There are few treatments that slow neurodegeneration in Alzheimer's disease (AD), and while therapeutic antibodies are being investigated in clinical trials for AD treatment, their access to the ...central nervous system is restricted by the blood-brain barrier. This study investigates a bispecific modular fusion protein composed of gantenerumab, a fully human monoclonal anti- amyloid-beta (Aβ) antibody under investigation for AD treatment, with a human transferrin receptor 1-directed Brainshuttle™ module (trontinemab; RG6102, INN trontinemab). In vitro, trontinemab showed a similar binding affinity to fibrillar Aβ
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and Aβ plaques in human AD brain sections to gantenerumab. A single intravenous administration of trontinemab (10 mg/kg) or gantenerumab (20 mg/kg) to non-human primates (NHPs, Macaca fascicularis), was well tolerated in both groups. Immunohistochemistry indicated increased trontinemab uptake into the brain endothelial cell layer and parenchyma, and more homogeneous distribution, compared with gantenerumab. Brain and plasma pharmacokinetic (PK) parameters for trontinemab were estimated by nonlinear mixed-effects modeling with correction for tissue residual blood, indicating a 4-18-fold increase in brain exposure. A previously developed clinical PK/pharmacodynamic model of gantenerumab was adapted to include a brain compartment as a driver of plaque removal and linked to the allometrically scaled above model from NHP. The new brain exposure-based model was used to predict trontinemab dosing regimens for effective amyloid reduction. Simulations from these models were used to inform dosing of trontinemab in the first-in-human clinical trial.
An anaerobic bacterium was isolated from a polluted sediment, with succinate and yeast extract as carbon and energy sources. The new strain was Gram-positive, the cells were coccal shaped, the mol% ...G+G content of the genomic DNA was 29, and the peptidoglycan was of the L-ornithine-D-glutamic acid type. Comparative sequence analysis of the 16S rRNA gene showed the new strain to belong to the genus Peptostreptococcus. Succinate, fumarate, pyruvate, 3-hydroxybutyrate and lysine supported growth. Succinate was degraded to propionate and presumably CO2, with a stoichiometric cell yield. Key enzymes of the methylmalonyl-CoA decarboxylase pathway were present. The methylmalonyl-CoA decarboxylase activity was avidin-sensitive and sodium dependent, and about 5 mM Na+ was required for maximal activity. Whole cells, however, required at least 50 mM sodium for maximal succinate decarboxylation activity and to support the maximum growth rate. Sodium-dependent energy conservation coupled to succinate decarboxylation is shown for the first time to occur in a bacterium belonging to the group of Gram-positive bacteria containing the peptostreptococci and their relatives.
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