167 research outputs found
537Microparticles and exosomes differentially impact on endothelial cell function in coronary artery disease
Background and Purpose: Microparticles (MPs) and exosomes are released by cells using different mechanisms. Thus, quantitative as well as qualitative changes of both particle populations, MPs and exosomes, in patients with coronary artery disease (CAD) might reflect an altered activation status of the endothelium, platelets and leukocytes. Moreover, they might exert differential effects on the target organs, such as the endothelium. Yet, alterations in both populations have not been studied side-by-side so far. The aim of the study was to compare the impact of MPs and exosomes from healthy subjects and CAD patients on endothelial cell (EC) functional characteristics. Methods: MPs and exosomes were isolated by stepwise filtration and ultracentrifugation from citrate-plasma and verified by electron microscopy and dynamic light scattering. MP and exosome fractions, as well as the vehicle (PBS), were added to human arterial ECs and EC apoptosis, number, size, capacity for in vitro-reendothelialisation after scratching, expression of adhesion molecules ICAM-1 and VCAM-1 were assessed. In parallel, platelet-, endothelial- and leukocyte-derived MPs were quantified. In a separate sub-study, the same parameters were assessed in plasma of CAD patients undergoing standard medical rehabilitation or an exercise-based cardiac rehabilitation programme. Results: MPs of healthy, but not of CAD patients supported in vitro re-endothelialisation, while exosomes had no influence. Exercise, but not standard rehabilitation improved CAD MP capacity to support in vitro rehabilitation. This was negatively correlated to the number of leukocyte- and endothelial-derived MPs, but not total or platelet MPs. EC number was negatively affected by exposure to CAD MPs. ANCOVA analysis identified disease, but not the particle type as influencing factor. Instead, apoptotic cell death was influenced by particle type, but not by the disease, and was not altered in rehabilitation. Similarly, ICAM-1 and VCAM-1 expression were enhanced on ECs after incubation with exosomes, but not with MPs, with no effect of disease or rehabilitation. Conclusion: MPs and exosomes differentially affect endothelial cell function and underlie differential modulation in disease and rehabilitation. Those findings might in the future help to optimize and monitor cardiovascular therap
The Boundary Multiplet of N=4 SU(2)xU(1) Gauged Supergravity on Asymptotically-AdS_5
We consider N=4 SU(2)xU(1) gauged supergravity on asymptotically-AdS_5
backgrounds. By a near-boundary analysis we determine the boundary-dominant
components of the bulk fields from their partially gauge-fixed field equations.
Subdominant components are projected out in the boundary limit and we find a
reduced set of boundary fields, constituting the N=2 Weyl multiplet. The
residual bulk symmetries are found to act on the boundary fields as
four-dimensional diffeomorphisms, N=2 supersymmetry and (super-)Weyl
transformations. This shows that the on-shell N=4 supergravity multiplet yields
the N=2 Weyl multiplet on the boundary with the appropriate local N=2
superconformal transformations. Building on these results we use the AdS/CFT
conjecture to calculate the Weyl anomaly of the dual four-dimensional
superconformal field theories in a generic bosonic N=2 conformal supergravity
background.Comment: 23 pages; to appear in JHE
The Schrdinger-Poisson equations as the large-N limit of the Newtonian N-body system: applications to the large scale dark matter dynamics
In this paper it is argued how the dynamics of the classical Newtonian N-body
system can be described in terms of the Schrdinger-Poisson equations
in the large limit. This result is based on the stochastic quantization
introduced by Nelson, and on the Calogero conjecture. According to the Calogero
conjecture, the emerging effective Planck constant is computed in terms of the
parameters of the N-body system as , where is the gravitational constant, and are the
number and the mass of the bodies, and is their average density. The
relevance of this result in the context of large scale structure formation is
discussed. In particular, this finding gives a further argument in support of
the validity of the Schrdinger method as numerical double of the
N-body simulations of dark matter dynamics at large cosmological scales.Comment: Accepted for publication in the Euro. Phys. J.
Inadequacy of zero-width approximation for a light Higgs boson signal
In the Higgs search at the LHC, a light Higgs boson (115 GeV <~ M_H <~ 130
GeV) is not excluded by experimental data. In this mass range, the width of the
Standard Model Higgs boson is more than four orders of magnitude smaller than
its mass. The zero-width approximation is hence expected to be an excellent
approximation. We show that this is not always the case. The inclusion of
off-shell contributions is essential to obtain an accurate Higgs signal
normalisation at the 1% precision level. For gg (-> H) -> VV, V= W,Z, O(10%)
corrections occur due to an enhanced Higgs signal in the region M_VV > 2 M_V,
where also sizable Higgs-continuum interference occurs. We discuss how
experimental selection cuts can be used to exclude this region in search
channels where the Higgs invariant mass cannot be reconstructed. We note that
the H -> VV decay modes in weak boson fusion are similarly affected.Comment: 26 pages, 18 figures, 6 tables; added references, expanded
introduction, version to appear in JHE
Euclid preparation. XXVIII. Forecasts for ten different higher-order weak lensing statistics
Recent cosmic shear studies have shown that higher-order statistics (HOS) developed by independent teams now outperform standard two-point estimators in terms of statistical precision thanks to their sensitivity to the non-Gaussian features of large-scale structure. The aim of the Higher-Order Weak Lensing Statistics (HOWLS) project is to assess, compare, and combine the constraining power of ten different HOS on a common set of Euclid-like mocks, derived from N-body simulations. In this first paper of the HOWLS series, we computed the nontomographic (Ω, σ) Fisher information for the one-point probability distribution function, peak counts, Minkowski functionals, Betti numbers, persistent homology Betti numbers and heatmap, and scattering transform coefficients, and we compare them to the shear and convergence two-point correlation functions in the absence of any systematic bias. We also include forecasts for three implementations of higher-order moments, but these cannot be robustly interpreted as the Gaussian likelihood assumption breaks down for these statistics. Taken individually, we find that each HOS outperforms the two-point statistics by a factor of around two in the precision of the forecasts with some variations across statistics and cosmological parameters. When combining all the HOS, this increases to a 4.5 times improvement, highlighting the immense potential of HOS for cosmic shear cosmological analyses with Euclid. The data used in this analysis are publicly released with the paper
Euclid Preparation. XXVIII. Forecasts for ten different higher-order weak lensing statistics
Recent cosmic shear studies have shown that higher-order statistics (HOS) developed by independent teams now outperform standard two-point estimators in terms of statistical precision thanks to their sensitivity to the non-Gaussian features of large-scale structure. The aim of the Higher-Order Weak Lensing Statistics (HOWLS) project is to assess, compare, and combine the constraining power of ten different HOS on a common set of -like mocks, derived from N-body simulations. In this first paper of the HOWLS series, we computed the nontomographic (, ) Fisher information for the one-point probability distribution function, peak counts, Minkowski functionals, Betti numbers, persistent homology Betti numbers and heatmap, and scattering transform coefficients, and we compare them to the shear and convergence two-point correlation functions in the absence of any systematic bias. We also include forecasts for three implementations of higher-order moments, but these cannot be robustly interpreted as the Gaussian likelihood assumption breaks down for these statistics. Taken individually, we find that each HOS outperforms the two-point statistics by a factor of around two in the precision of the forecasts with some variations across statistics and cosmological parameters. When combining all the HOS, this increases to a times improvement, highlighting the immense potential of HOS for cosmic shear cosmological analyses with . The data used in this analysis are publicly released with the paper
Biomarker-indicated extent of oxidation of plant-derived organic carbon (OC) in relation to geomorphology in an arsenic contaminated Holocene aquifer, Cambodia
The poisoning of rural populations in South and Southeast Asia due to high groundwater arsenic concentrations is one of the world’s largest ongoing natural disasters. It is important to consider environmental processes related to the release of geogenic arsenic, including geomorphological and organic geochemical processes. Arsenic is released from sediments when iron-oxide minerals, onto which arsenic is adsorbed or incorporated, react with organic carbon (OC) and the OC is oxidised. In this study we build a new geomorphological framework for Kandal Province, a highly studied arsenic affected region of Cambodia, and tie this into wider regional environmental change throughout the Holocene. Analyses shows that the concentration of OC in the sediments is strongly inversely correlated to grainsize. Furthermore, the type of OC is also related to grain size with the clay containing mostly (immature) plant derived OC and sand containing mostly thermally mature derived OC. Finally, analyses indicate that within the plant derived OC relative oxidation is strongly grouped by stratigraphy with the older bound OC more oxidised than younger OC
Ca2+ monitoring in Plasmodium falciparum using the yellow cameleon-Nano biosensor
Calcium (Ca2+)-mediated signaling is a conserved mechanism in eukaryotes, including the human malaria parasite, Plasmodium falciparum. Due to its small size (300?nM). We determined that the mammalian SERCA inhibitor thapsigargin and antimalarial dihydroartemisinin did not perturb SERCA activity. The change of the cytosolic Ca2+ level in P. falciparum was additionally detectable by flow cytometry. Thus, we propose that the developed YC-Nano-based system is useful to study Ca2+ signaling in P. falciparum and is applicable for drug screening.We are grateful to Japanese Red Cross Blood Society for providing human RBC and plasma. We also thank Tanaka R, Ogoshi (Sakura) M and Matsumoto N for technical assistance and Templeton TJ for critical reading. This study was conducted at the Joint Usage / Research Center on Tropical Disease, Institute of Tropical Medicine, Nagasaki University, Japan. KP was a Tokyo Biochemical Research Foundation (TBRF, http://www.tokyobrf.or.jp) post-doctoral fellow and PEF was a Japanese Society of Promotion Sciences (JSPS) post-doctoral fellow. This work was supported in part by the TBRF (K.P.), JSPS (P.E.F.), Takeda Science Foundation (K.Y.), Grants-in-Aids for Scientific Research 24590509 (K.Y.), 22390079 (O.K.), and for Scientific Research on Innovative Areas 23117008 (O.K.), MEXT, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Novel Polymorphisms in Plasmodium falciparum ABC Transporter Genes Are Associated with Major ACT Antimalarial Drug Resistance
Chemotherapy is a critical component of malaria control. However, the most deadly malaria pathogen, Plasmodium falciparum, has repeatedly mounted resistance against a series of antimalarial drugs used in the last decades. Southeast Asia is an epicenter of emerging antimalarial drug resistance, including recent resistance to the artemisinins, the core component of all recommended antimalarial combination therapies. Alterations in the parasitic membrane proteins Pgh-1, PfCRT and PfMRP1 are believed to be major contributors to resistance through decreasing intracellular drug accumulation. The pfcrt, pfmdr1 and pfmrp1 genes were sequenced from a set of P.falciparum field isolates from the Thai-Myanmar border. In vitro drug susceptibility to artemisinin, dihydroartemisinin, mefloquine and lumefantrine were assessed. Positive correlations were seen between the in vitro susceptibility responses to artemisinin and dihydroartemisinin and the responses to the arylamino-alcohol quinolines lumefantrine and mefloquine. The previously unstudied pfmdr1 F1226Y and pfmrp1 F1390I SNPs were associated significantly with artemisinin, mefloquine and lumefantrine in vitro susceptibility. A variation in pfmdr1 gene copy number was also associated with parasite drug susceptibility of artemisinin, mefloquine and lumefantrine. Our work unveils new candidate markers of P. falciparum multidrug resistance in vitro, while contributing to the understanding of subjacent genetic complexity, essential for future evidence-based drug policy decisions
Euclid Preparation. XXVIII. Forecasts for ten different higher-order weak lensing statistics
Recent cosmic shear studies have shown that higher-order statistics (HOS)
developed by independent teams now outperform standard two-point estimators in
terms of statistical precision thanks to their sensitivity to the non-Gaussian
features of large-scale structure. The aim of the Higher-Order Weak Lensing
Statistics (HOWLS) project is to assess, compare, and combine the constraining
power of ten different HOS on a common set of -like mocks, derived from
N-body simulations. In this first paper of the HOWLS series, we computed the
nontomographic (, ) Fisher information for the
one-point probability distribution function, peak counts, Minkowski
functionals, Betti numbers, persistent homology Betti numbers and heatmap, and
scattering transform coefficients, and we compare them to the shear and
convergence two-point correlation functions in the absence of any systematic
bias. We also include forecasts for three implementations of higher-order
moments, but these cannot be robustly interpreted as the Gaussian likelihood
assumption breaks down for these statistics. Taken individually, we find that
each HOS outperforms the two-point statistics by a factor of around two in the
precision of the forecasts with some variations across statistics and
cosmological parameters. When combining all the HOS, this increases to a
times improvement, highlighting the immense potential of HOS for cosmic shear
cosmological analyses with . The data used in this analysis are
publicly released with the paper.Comment: 33 pages, 24 figures, main results in Fig. 19 & Table 5, version
published in A&
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