933 research outputs found
Immunosenescence, Inflammaging, and Frailty: Role of Myeloid Cells in Age-Related Diseases
The immune system is the central regulator of tissue homeostasis, ensuring tissue regeneration and protection against both pathogens and the neoformation of cancer cells. Its proper functioning requires homeostatic properties, which are maintained by an adequate balance of myeloid and lymphoid responses. Aging progressively undermines this ability and compromises the correct activation of immune responses, as well as the resolution of the inflammatory response. A subclinical syndrome of “homeostatic frailty” appears as a distinctive trait of the elderly, which predisposes to immune debilitation and chronic low-grade inflammation (inflammaging), causing the uncontrolled development of chronic and degenerative diseases. The innate immune compartment, in particular, undergoes to a sequela of age-dependent functional alterations, encompassing steps of myeloid progenitor differentiation and altered responses to endogenous and exogenous threats. Here, we will review the age-dependent evolution of myeloid populations, as well as their impact on frailty and diseases of the elderly
Myeloid-derived suppressor cells: Ductile targets in disease
Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells with major regulatory functions and rise during pathological conditions, including cancer, infections and autoimmune conditions. MDSC expansion is generally linked to inflammatory processes that emerge in response to stable immunological stress, which alter both magnitude and quality of the myelopoietic output. Inability to reinstate physiological myelopoiesis would fall in an "emergency state" that perpetually reprograms myeloid cells toward suppressive functions. While differentiation and reprogramming of myeloid cells toward an immunosuppressive phenotype can be considered the result of a multistep process that originates in the bone marrow and culminates in the tumor microenvironment, the identification of its driving events may offer potential therapeutic approaches in different pathologies. Indeed, whereas expansion of MDSCs, in both murine and human tumor bearers, results in reduced immune surveillance and antitumor cytotoxicity, placing an obstacle to the effectiveness of anticancer therapies, adoptive transfer of MDSCs has shown therapeutic benefits in autoimmune disorders. Here, we describe relevant mechanisms of myeloid cell reprogramming leading to generation of suppressive MDSCs and discuss their therapeutic ductility in disease
Effects of nuclear re-interactions in quasi-elastic neutrino-nucleus scattering
The effects of nuclear re-interactions in the quasi-elastic neutrino-nucleus
scattering are investigated with a phenomenological model. We found that the
nuclear responses are lowered and their maxima are shifted towards higher
excitation energies. This is reflected on the total neutrino-nucleus cross
section in a general reduction of about 15% for neutrino energies above 300
MeV.Comment: 15 pages, 5 figures. Submitted to AstroParticle Physic
Neutral-Current Atmospheric Neutrino Flux Measurement Using Neutrino-Proton Elastic Scattering in Super-Kamiokande
Recent results show that atmospheric oscillate with eV and , and that
conversion into is strongly disfavored. The Super-Kamiokande (SK)
collaboration, using a combination of three techniques, reports that their data
favor over . This distinction
is extremely important for both four-neutrino models and cosmology. We propose
that neutrino-proton elastic scattering () in water
\v{C}erenkov detectors can also distinguish between active and sterile
oscillations. This was not previously recognized as a useful channel since only
about 2% of struck protons are above the \v{C}erenkov threshold. Nevertheless,
in the present SK data there should be about 40 identifiable events. We show
that these events have unique particle identification characteristics, point in
the direction of the incoming neutrinos, and correspond to a narrow range of
neutrino energies (1-3 GeV, oscillating near the horizon). This channel will be
particularly important in Hyper-Kamiokande, with times higher rate.
Our results have other important applications. First, for a similarly small
fraction of atmospheric neutrino quasielastic events, the proton is
relativistic. This uniquely selects (not ) events,
useful for understanding matter effects, and allows determination of the
neutrino energy and direction, useful for the dependence of oscillations.
Second, using accelerator neutrinos, both elastic and quasielastic events with
relativistic protons can be seen in the K2K 1-kton near detector and MiniBooNE.Comment: 10 pages RevTeX, 8 figure
Heme catabolism by tumor-associated macrophages controls metastasis formation
Although the pathological significance of tumor-associated macrophage (TAM) heterogeneity is still poorly understood, TAM reprogramming is viewed as a promising anticancer therapy. Here we show that a distinct subset of TAMs (F4/80hiCD115hiC3aRhiCD88hi), endowed with high rates of heme catabolism by the stress-responsive enzyme heme oxygenase-1 (HO-1), plays a critical role in shaping a prometastatic tumor microenvironment favoring immunosuppression, angiogenesis and epithelial-to-mesenchymal transition. This population originates from F4/80+HO-1+ bone marrow (BM) precursors, accumulates in the blood of tumor bearers and preferentially localizes at the invasive margin through a mechanism dependent on the activation of Nrf2 and coordinated by the NF-κB1–CSF1R–C3aR axis. Inhibition of F4/80+HO-1+ TAM recruitment or myeloid-specific deletion of HO-1 blocks metastasis formation and improves anticancer immunotherapy. Relative expression of HO-1 in peripheral monocyte subsets, as well as in tumor lesions, discriminates survival among metastatic melanoma patients. Overall, these results identify a distinct cancer-induced HO-1+ myeloid subgroup as a new antimetastatic target and prognostic blood marker
Calibration of the Logarithmic-Periodic Dipole Antenna (LPDA) Radio Stations at the Pierre Auger Observatory using an Octocopter
An in-situ calibration of a logarithmic periodic dipole antenna with a
frequency coverage of 30 MHz to 80 MHz is performed. Such antennas are part of
a radio station system used for detection of cosmic ray induced air showers at
the Engineering Radio Array of the Pierre Auger Observatory, the so-called
Auger Engineering Radio Array (AERA). The directional and frequency
characteristics of the broadband antenna are investigated using a remotely
piloted aircraft (RPA) carrying a small transmitting antenna. The antenna
sensitivity is described by the vector effective length relating the measured
voltage with the electric-field components perpendicular to the incoming signal
direction. The horizontal and meridional components are determined with an
overall uncertainty of 7.4^{+0.9}_{-0.3} % and 10.3^{+2.8}_{-1.7} %
respectively. The measurement is used to correct a simulated response of the
frequency and directional response of the antenna. In addition, the influence
of the ground conductivity and permittivity on the antenna response is
simulated. Both have a negligible influence given the ground conditions
measured at the detector site. The overall uncertainties of the vector
effective length components result in an uncertainty of 8.8^{+2.1}_{-1.3} % in
the square root of the energy fluence for incoming signal directions with
zenith angles smaller than 60{\deg}.Comment: Published version. Updated online abstract only. Manuscript is
unchanged with respect to v2. 39 pages, 15 figures, 2 table
Azimuthal asymmetry in the risetime of the surface detector signals of the Pierre Auger Observatory
The azimuthal asymmetry in the risetime of signals in Auger surface detector
stations is a source of information on shower development. The azimuthal
asymmetry is due to a combination of the longitudinal evolution of the shower
and geometrical effects related to the angles of incidence of the particles
into the detectors. The magnitude of the effect depends upon the zenith angle
and state of development of the shower and thus provides a novel observable,
, sensitive to the mass composition of cosmic rays
above eV. By comparing measurements with predictions from
shower simulations, we find for both of our adopted models of hadronic physics
(QGSJETII-04 and EPOS-LHC) an indication that the mean cosmic-ray mass
increases slowly with energy, as has been inferred from other studies. However,
the mass estimates are dependent on the shower model and on the range of
distance from the shower core selected. Thus the method has uncovered further
deficiencies in our understanding of shower modelling that must be resolved
before the mass composition can be inferred from .Comment: Replaced with published version. Added journal reference and DO
Multi-resolution anisotropy studies of ultrahigh-energy cosmic rays detected at the Pierre Auger Observatory
We report a multi-resolution search for anisotropies in the arrival
directions of cosmic rays detected at the Pierre Auger Observatory with local
zenith angles up to and energies in excess of 4 EeV ( eV). This search is conducted by measuring the angular power spectrum
and performing a needlet wavelet analysis in two independent energy ranges.
Both analyses are complementary since the angular power spectrum achieves a
better performance in identifying large-scale patterns while the needlet
wavelet analysis, considering the parameters used in this work, presents a
higher efficiency in detecting smaller-scale anisotropies, potentially
providing directional information on any observed anisotropies. No deviation
from isotropy is observed on any angular scale in the energy range between 4
and 8 EeV. Above 8 EeV, an indication for a dipole moment is captured; while no
other deviation from isotropy is observed for moments beyond the dipole one.
The corresponding -values obtained after accounting for searches blindly
performed at several angular scales, are in the case of
the angular power spectrum, and in the case of the needlet
analysis. While these results are consistent with previous reports making use
of the same data set, they provide extensions of the previous works through the
thorough scans of the angular scales.Comment: Published version. Added journal reference and DOI. Added Report
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Ultrahigh-energy neutrino follow-up of Gravitational Wave events GW150914 and GW151226 with the Pierre Auger Observatory
On September 14, 2015 the Advanced LIGO detectors observed their first
gravitational-wave (GW) transient GW150914. This was followed by a second GW
event observed on December 26, 2015. Both events were inferred to have arisen
from the merger of black holes in binary systems. Such a system may emit
neutrinos if there are magnetic fields and disk debris remaining from the
formation of the two black holes. With the surface detector array of the Pierre
Auger Observatory we can search for neutrinos with energy above 100 PeV from
point-like sources across the sky with equatorial declination from about -65
deg. to +60 deg., and in particular from a fraction of the 90% confidence-level
(CL) inferred positions in the sky of GW150914 and GW151226. A targeted search
for highly-inclined extensive air showers, produced either by interactions of
downward-going neutrinos of all flavors in the atmosphere or by the decays of
tau leptons originating from tau-neutrino interactions in the Earth's crust
(Earth-skimming neutrinos), yielded no candidates in the Auger data collected
within s around or 1 day after the coordinated universal time (UTC)
of GW150914 and GW151226, as well as in the same search periods relative to the
UTC time of the GW candidate event LVT151012. From the non-observation we
constrain the amount of energy radiated in ultrahigh-energy neutrinos from such
remarkable events.Comment: Published version. Added journal reference and DOI. Added Report
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