215 research outputs found
Fermionic Wigs for AdS-Schwarzschild Black Holes
We provide the metric, the gravitino fields and the gauge fields to all
orders in the fermionic zero modes for D=5 and D=4, N=2 gauged supergravity
solutions starting from non-extremal AdS--Schwarzschild black holes. We compute
the Brown-York stress--energy tensor on the boundary of AdS_5 / AdS_4 spaces
and we discuss some implications of the fermionic corrections to perfect fluid
interpretation of the boundary theory. The complete non-linear solution, which
we denote as fermionic wig, is achieved by acting with supersymmetry
transformations upon the supergravity fields and that expansion naturally
truncates at some order in the fermionic zero modes.Comment: 27 pages, Latex2e, no figures, 3 ancillary file
Microparticles from apoptotic platelets promote resident macrophage differentiation
Platelets shed microparticles not only upon activation, but also upon ageing by an apoptosis-like process (apoptosis-induced platelet microparticles, PMap). While the activation-induced microparticles have widely been studied, not much is known about the (patho)physiological consequences of PMap formation. Flow cytometry and scanning electron microscopy demonstrated that PMap display activated integrins and interact to form microparticle aggregates. PMap were chemotactic for monocytic cells, bound to these cells, an furthermore stimulated cell adhesion and spreading on a fibronectin surface. After prolonged incubation, PMap promoted cell differentiation, but inhibited proliferation. Monocyte membrane receptor analysis revealed increased expression levels of CD11b (integrin αMβ2), CD14 and CD31 (platelet endothelial cell adhesion molecule-1), and the chemokine receptors CCR5 and CXCR4, but not of CCR2. This indicated that PMap polarized the cells into resident M2 monocytes. Cells treated with PMap actively consumed oxidized low-density lipoprotein (oxLDL), and released matrix metalloproteinases and hydrogen peroxide. Further confirmation for the differentiation towards resident professional phagocytes came from the finding that PMap stimulated the expression of the (ox)LDL receptors, CD36 and CD68, and the production of proinflammatory and immunomodulating cytokines by monocytes. In conclusion, interaction of PMap with monocytic cells has an immunomodulating potential. The apoptotic microparticles polarize the cells into a resident M2 subset, and induce differentiation to resident professional phagocytes
Contribution of Recipient-Derived Cells in Allograft Neointima Formation and the Response to Stent Implantation
Allograft coronary disease is the dominant cause of increased risk of death after cardiac transplantation. While the percutaneous insertion of stents is the most efficacious revascularization strategy for allograft coronary disease there is a high incidence of stent renarrowing. We developed a novel rabbit model of sex-mismatched allograft vascular disease as well as the response to stent implantation. In situ hybridization for the Y-chromosome was employed to detect male cells in the neointima of stented allograft, and the population of recipient derived neointimal cells was measured by quantitative polymerase chain reaction and characterized by immunohistochemistry. To demonstrate the participation of circulatory derived cells in stent neointima formation we infused ex vivo labeled peripheral blood mononuclear cells into native rabbit carotid arteries immediately after stenting. Fourteen days after stenting the neointima area was 58% greater in the stented vs. non-stented allograft segments (p = 0.02). Male cells were detected in the neointima of stented female-to-male allografts. Recipient-derived cells constituted 72.1±5.7% and 81.5±4.2% of neointimal cell population in the non-stented and stented segments, respectively and the corresponding proliferation rates were only 2.7±0.5% and 2.3±0.2%. Some of the recipient-derived neointimal cells were of endothelial lineage. The ex vivo tagged cells constituted 9.0±0.4% of the cells per high power field in the stent neointima 14 days after stenting. These experiments provide important quantitative data regarding the degree to which host-derived blood-borne cells contribute to neointima formation in allograft vasculopathy and the early response to stent implantation
Suppression of Lung Adenocarcinoma Progression by Nkx2-1
Despite the high prevalence and poor outcome of patients with
metastatic lung cancer the mechanisms of tumour progression and
metastasis remain largely uncharacterized. Here we modelled
human lung adenocarcinoma, which frequently harbours activating
point mutations in KRAS and inactivation of the p53 pathway,
using conditional alleles in mice. Lentiviral-mediated somatic
activation of oncogenic Kras and deletion of p53 in the lung epithelial
cells of Kras[superscript LSL-G12D/+];p53[superscript flox/flox] mice initiates lung adenocarcinoma
development4. Although tumours are initiated synchronously
by defined genetic alterations, only a subset becomes malignant,
indicating that disease progression requires additional alterations.
Identification of the lentiviral integration sites allowed us to distinguish
metastatic from non-metastatic tumours and determine the
gene expression alterations that distinguish these tumour types.
Cross-species analysis identified the NK2-related homeobox transcription
factor Nkx2-1 (also called Ttf-1 or Titf1) as a candidate
suppressor of malignant progression. In this mouse model, Nkx2-1
negativity is pathognomonic of high-grade poorly differentiated
tumours. Gain- and loss-of-function experiments in cells derived
from metastatic and non-metastatic tumours demonstrated that
Nkx2-1 controls tumour differentiation and limitsmetastatic potential
in vivo. Interrogation of Nkx2-1-regulated genes, analysis of
tumours at defined developmental stages, and functional complementation
experiments indicate that Nkx2-1 constrains tumours in
part by repressing the embryonically restricted chromatin regulator
Hmga2. Whereas focal amplification of NKX2-1 in a fraction of
human lung adenocarcinomas has focused attention on its oncogenic
function, our data specifically link Nkx2-1 downregulation
to loss of differentiation, enhanced tumour seeding ability and
increased metastatic proclivity. Thus, the oncogenic and suppressive
functions ofNkx2-1 in the sametumourNational Institutes of Health (U.S.) (grant U01-CA84306 )National Institutes of Health (U.S.) (grant K99-CA151968)Howard Hughes Medical InstituteLudwig Center for Molecular OncologyNational Cancer Institute (U.S.) (Cancer Center Support (core) grant P30-CA14051
Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles
Release of membrane vesicles, a process conserved in both prokaryotes and eukaryotes, represents an evolutionary link, and suggests essential functions of a dynamic extracellular vesicular compartment (including exosomes, microparticles or microvesicles and apoptotic bodies). Compelling evidence supports the significance of this compartment in a broad range of physiological and pathological processes. However, classification of membrane vesicles, protocols of their isolation and detection, molecular details of vesicular release, clearance and biological functions are still under intense investigation. Here, we give a comprehensive overview of extracellular vesicles. After discussing the technical pitfalls and potential artifacts of the rapidly emerging field, we compare results from meta-analyses of published proteomic studies on membrane vesicles. We also summarize clinical implications of membrane vesicles. Lessons from this compartment challenge current paradigms concerning the mechanisms of intercellular communication and immune regulation. Furthermore, its clinical implementation may open new perspectives in translational medicine both in diagnostics and therapy
Cosmological Fast Optical Transients with the Zwicky Transient Facility: A Search for Dirty Fireballs
Dirty fireballs are a hypothesized class of relativistic massive-star explosions with an initial Lorentz factor Γinit below the Γinit ∼ 100 required to produce a long-duration gamma-ray burst (LGRB), but which could still produce optical emission resembling LGRB afterglows. Here we present the results of a search for on-axis optical afterglows using the Zwicky Transient Facility (ZTF). Our search yielded seven optical transients that resemble on-axis LGRB afterglows in terms of their red colors (g − r > 0 mag), faint host galaxies (r > 23 mag), rapid fading (dr/dt > 1 mag day−1), and in some cases X-ray and radio emission. Spectroscopy of the transient emission within a few days of discovery established cosmological distances (redshift z = 0.876 to 2.9) for six of the seven events, tripling the number of afterglows with redshift measurements discovered by optical surveys without a γ-ray trigger. A likely associated LGRB (GRB 200524A, GRB 210204A, GRB 210212B, and GRB 210610B) was identified for four events (ZTF 20abbiixp/AT 2020kym, ZTF 21aagwbjr/AT 2021buv, ZTF 21aakruew/AT 2021cwd, and ZTF 21abfmpwn/AT 2021qbd) post facto, while three (ZTF 20aajnksq/AT 2020blt, ZTF 21aaeyldq/AT 2021any, and ZTF 21aayokph/AT 2021lfa) had no detected LGRB counterpart. The simplest explanation for the three “orphan” events is that they were regular LGRBs missed by high-energy satellites owing to detector sensitivity and duty cycle, although it is possible that they were intrinsically subluminous in γ-rays or viewed slightly off-axis. We rule out a scenario in which dirty fireballs have a similar energy per solid angle to LGRBs and are an order of magnitude more common. In addition, we set the first direct constraint on the ratio of the opening angles of the material producing γ-rays and the material producing early optical afterglow emission, finding that they must be comparable
First measurement of the |t|-dependence of coherent J/ψ photonuclear production
The first measurement of the cross section for coherent J/ψ photoproduction as a function of |t|, the square of the momentum transferred between the incoming and outgoing target nucleus, is presented. The data were measured with the ALICE detector in ultra-peripheral Pb–Pb collisions at a centre-of-mass energy per nucleon pair sNN=5.02TeV with the J/ψ produced in the central rapidity region |y|<0.8, which corresponds to the small Bjorken-x range (0.3−1.4)×10−3.
The measured |t|-dependence is not described by computations based only on the Pb nuclear form factor, while the photonuclear cross section is better reproduced by models including shadowing according to the leading-twist approximation, or gluon-saturation effects from the impact-parameter dependent Balitsky–Kovchegov equation. These new results are therefore a valid tool to constrain the relevant model parameters and to investigate the transverse gluonic structure at very low Bjorken-x.publishedVersio
First measurement of coherent ρ0 photoproduction in ultra-peripheral Xe–Xe collisions at √sNN = 5.44 TeV
The first measurement of the coherent photoproduction of ρ0 vector mesons in ultra-peripheral Xe–Xe collisions at sNN=5.44 TeV is presented. This result, together with previous HERA γp data and γ–Pb measurements from ALICE, describes the atomic number (A) dependence of this process, which is particularly sensitive to nuclear shadowing effects and to the approach to the black-disc limit of QCD at a semi-hard scale. The cross section of the Xe+Xe→ρ0+Xe+Xe process, measured at midrapidity through the decay channel ρ0→π+π−, is found to be dσ/dy=131.5±5.6(stat.)−16.9+17.5(syst.) mb. The ratio of the continuum to resonant contributions for the production of pion pairs is also measured. In addition, the fraction of events accompanied by electromagnetic dissociation of either one or both colliding nuclei is reported. The dependence on A of cross section for the coherent ρ0 photoproduction at a centre-of-mass energy per nucleon of the γA system of WγA,n=65 GeV is found to be consistent with a power-law behaviour σ(γA→ρ0A)∝Aα with a slope α=0.96±0.02(syst.). This slope signals important shadowing effects, but it is still far from the behaviour expected in the black-disc limit.publishedVersio
Higher harmonic anisotropic flow measurements of charged particles in Pb-Pb collisions at 2.76 TeV
We report on the first measurement of the triangular , quadrangular
, and pentagonal charged particle flow in Pb-Pb collisions at 2.76
TeV measured with the ALICE detector at the CERN Large Hadron Collider. We show
that the triangular flow can be described in terms of the initial spatial
anisotropy and its fluctuations, which provides strong constraints on its
origin. In the most central events, where the elliptic flow and
have similar magnitude, a double peaked structure in the two-particle azimuthal
correlations is observed, which is often interpreted as a Mach cone response to
fast partons. We show that this structure can be naturally explained from the
measured anisotropic flow Fourier coefficients.Comment: 10 pages, 4 figures, published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/387
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