90 research outputs found
Anarchy and Neutrino Physics
The neutrino sector of a seesaw-extended Standard Model is investigated under
the anarchy hypothesis. The previously derived probability density functions
for neutrino masses and mixings, which characterize the type I-III seesaw
ensemble of complex random matrices, are used to extract
information on the relevant physical parameters. For and , the
distributions of the light neutrino masses, as well as the mixing angles and
phases, are obtained using numerical integration methods. A systematic
comparison with the much simpler type II seesaw ensemble is also performed to
point out the fundamental differences between the two ensembles. It is found
that the type I-III seesaw ensemble is better suited to accommodate
experimental data. Moreover, the results indicate a strong preference for the
mass splitting associated to normal hierarchy. However, since all permutations
of the singular values are found to be equally probable for a particular mass
splitting, predictions regarding the hierarchy of the mass spectrum remains out
of reach in the framework of anarchy.Comment: 1+22 pages, 8 figures, typos fixed, added referenc
Probability Density Functions for CP-Violating Rephasing Invariants
The implications of the anarchy principle on CP violation in the lepton
sector are investigated. A systematic method is introduced to compute the
probability density functions for the CP-violating rephasing invariants of the
PMNS matrix from the Haar measure relevant to the anarchy principle. Contrary
to the CKM matrix which is hierarchical, it is shown that the Haar measure, and
hence the anarchy principle, are very likely to lead to the observed PMNS
matrix. Predictions on the CP-violating Dirac rephasing invariant and
Majorana rephasing invariant are also obtained. They correspond to
and
respectively, in
agreement with the experimental hint from T2K of
(or ) for the
normal (or inverted) hierarchy.Comment: 1+15 pages, 2 figure
Extreme faint flux imaging with an EMCCD
An EMCCD camera, designed from the ground up for extreme faint flux imaging,
is presented. CCCP, the CCD Controller for Counting Photons, has been
integrated with a CCD97 EMCCD from e2v technologies into a scientific camera at
the Laboratoire d'Astrophysique Experimentale (LAE), Universite de Montreal.
This new camera achieves sub-electron read-out noise and very low Clock Induced
Charge (CIC) levels, which are mandatory for extreme faint flux imaging. It has
been characterized in laboratory and used on the Observatoire du Mont Megantic
1.6-m telescope. The performance of the camera is discussed and experimental
data with the first scientific data are presented.Comment: 33 pages, 17 figures, accepted for publication in PAS
Vascular smooth muscle contractility assays for inflammatory and immunological mediators
The blood vessels are one of the important target tissues for the mediators of inflammation and allergy; further cytokines affect them in a number of ways. We review the use of the isolated blood vessel mounted in organ baths as an important source of pharmacological information. While its use in the bioassay of vasoactive substances tends to be replaced with modern analytical techniques, contractility assays are effective to evaluate novel synthetic drugs, generating robust potency and selectivity data about agonists, partial agonists and competitive or insurmountable antagonists. For instance, the human umbilical vein has been used extensively to characterize ligands of the bradykinin B2 receptors. Isolated vascular segments are live tissues that are intensely reactive, notably with the regulated expression of gene products relevant for inflammation (e.g., the kinin B1 receptor and inducible nitric oxide synthase). Further, isolated vessels can be adapted as assays of unconventional proteins (cytokines such as interleukin-1, proteases of physiopathological importance, complement-derived anaphylatoxins and recombinant hemoglobin) and to the gene knockout technology. The well known cross-talks between different cell types, e.g., endothelium-muscle and nerve terminal-muscle, can be extended (smooth muscle cell interaction with resident or infiltrating leukocytes and tumor cells). Drug metabolism and distribution problems can be modeled in a useful manner using the organ bath technology, which, for all these reasons, opens a window on an intermediate level of complexity relative to cellular and molecular pharmacology on one hand, and in vivo studies on the other
Cancer risk factors in systemic lupus erythematosus: multivariate regression analysis in 16,409 patients
Fermi Large Area Telescope View of the Core of the Radio Galaxy Centaurus A
We present gamma-ray observations with the LAT on board the Fermi Gamma-Ray
Telescope of the nearby radio galaxy Centaurus~A. The previous EGRET detection
is confirmed, and the localization is improved using data from the first 10
months of Fermi science operation. In previous work, we presented the detection
of the lobes by the LAT; in this work, we concentrate on the gamma-ray core of
Cen~A. Flux levels as seen by the LAT are not significantly different from that
found by EGRET, nor is the extremely soft LAT spectrum
(\G=2.67\pm0.10_{stat}\pm0.08_{sys} where the photon flux is \Phi\propto
E^{-\G}). The LAT core spectrum, extrapolated to higher energies, is
marginally consistent with the non-simultaneous HESS spectrum of the source.
The LAT observations are complemented by simultaneous observations from Suzaku,
the Swift Burst Alert Telescope and X-ray Telescope, and radio observations
with the Tracking Active Galactic Nuclei with Austral Milliarcsecond
Interferometry (TANAMI) program, along with a variety of non-simultaneous
archival data from a variety of instruments and wavelengths to produce a
spectral energy distribution (SED). We fit this broadband data set with a
single-zone synchrotron/synchrotron self-Compton model, which describes the
radio through GeV emission well, but fails to account for the non-simultaneous
higher energy TeV emission observed by HESS from 2004-2008. The fit requires a
low Doppler factor, in contrast to BL Lacs which generally require larger
values to fit their broadband SEDs. This indicates the \g-ray emission
originates from a slower region than that from BL Lacs, consistent with
previous modeling results from Cen~A. This slower region could be a slower
moving layer around a fast spine, or a slower region farther out from the black
hole in a decelerating flow.Comment: Accepted by ApJ. 32 pages, 5 figures, 2 tables. J. Finke and Y.
Fukazawa corresponding author
Efficient Production of HIV-1 Virus-Like Particles from a Mammalian Expression Vector Requires the N-Terminal Capsid Domain
It is now well accepted that the structural protein Pr55Gag is sufficient by itself to produce HIV-1 virus-like particles (VLPs). This polyprotein precursor contains different domains including matrix, capsid, SP1, nucleocapsid, SP2 and p6. In the present study, we wanted to determine by mutagenesis which region(s) is essential to the production of VLPs when Pr55Gag is inserted in a mammalian expression vector, which allows studying the protein of interest in the absence of other viral proteins. To do so, we first studied a minimal Pr55Gag sequence called Gag min that was used previously. We found that Gag min fails to produce VLPs when expressed in an expression vector instead of within a molecular clone. This failure occurs early in the cell at the assembly of viral proteins. We then generated a series of deletion and substitution mutants, and examined their ability to produce VLPs by combining biochemical and microscopic approaches. We demonstrate that the matrix region is not necessary, but that the efficiency of VLP production depends strongly on the presence of its basic region. Moreover, the presence of the N-terminal domain of capsid is required for VLP production when Gag is expressed alone. These findings, combined with previous observations indicating that HIV-1 Pr55Gag-derived VLPs act as potent stimulators of innate and acquired immunity, make the use of this strategy worth considering for vaccine development
Induction of Selective Blood-Tumor Barrier Permeability and Macromolecular Transport by a Biostable Kinin B1 Receptor Agonist in a Glioma Rat Model
Treatment of malignant glioma with chemotherapy is limited mostly because of delivery impediment related to the blood-brain tumor barrier (BTB). B1 receptors (B1R), inducible prototypical G-protein coupled receptors (GPCR) can regulate permeability of vessels including possibly that of brain tumors. Here, we determine the extent of BTB permeability induced by the natural and synthetic peptide B1R agonists, LysdesArg9BK (LDBK) and SarLys[dPhe8]desArg9BK (NG29), in syngeneic F98 glioma-implanted Fischer rats. Ten days after tumor inoculation, we detected the presence of B1R on tumor cells and associated vasculature. NG29 infusion increased brain distribution volume and uptake profiles of paramagnetic probes (Magnevist and Gadomer) at tumoral sites (T1-weighted imaging). These effects were blocked by B1R antagonist and non-selective cyclooxygenase inhibitors, but not by B2R antagonist and non-selective nitric oxide synthase inhibitors. Consistent with MRI data, systemic co-administration of NG29 improved brain tumor delivery of Carboplatin chemotherapy (ICP-Mass spectrometry). We also detected elevated B1R expression in clinical samples of high-grade glioma. Our results documented a novel GPCR-signaling mechanism for promoting transient BTB disruption, involving activation of B1R and ensuing production of COX metabolites. They also underlined the potential value of synthetic biostable B1R agonists as selective BTB modulators for local delivery of different sized-therapeutics at (peri)tumoral sites
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