366 research outputs found
The Geometry of Integrable and Superintegrable Systems
The group of automorphisms of the geometry of an integrable system is
considered. The geometrical structure used to obtain it is provided by a normal
form representation of integrable systems that do not depend on any additional
geometrical structure like symplectic, Poisson, etc. Such geometrical structure
provides a generalized toroidal bundle on the carrier space of the system.
Non--canonical diffeomorphisms of such structure generate alternative
Hamiltonian structures for complete integrable Hamiltonian systems. The
energy-period theorem provides the first non--trivial obstruction for the
equivalence of integrable systems
BACE1 activity regulates cell surface contactin-2 levels
Background: Although BACE1 is a major therapeutic target for Alzheimer’s disease (AD), potential side effects of BACE1 inhibition are not well characterized. BACE1 cleaves over 60 putative substrates, however the majority of these cleavages have not been characterized. Here we investigated BACE1-mediated cleavage of human contactin-2, a GPI-anchored cell adhesion molecule. Results: Our initial protein sequence analysis showed that contactin-2 harbors a strong putative BACE1 cleavage site close to its GPI membrane linker domain. When we overexpressed BACE1 in CHO cells stably transfected with human contactin-2, we found increased release of soluble contactin-2 in the conditioned media. Conversely, pharmacological inhibition of BACE1 in CHO cells expressing human contactin-2 and mouse primary neurons decreased soluble contactin-2 secretion. The BACE1 cleavage site mutation 1008MM/AA dramatically impaired soluble contactin-2 release. We then asked whether contactin-2 release induced by BACE1 expression would concomitantly decrease cell surface levels of contactin-2. Using immunofluorescence and surface-biotinylation assays, we showed that BACE1 activity tightly regulates contactin-2 surface levels in CHO cells as well as in mouse primary neurons. Finally, contactin-2 levels were decreased in Alzheimer’s disease brain samples correlating inversely with elevated BACE1 levels in the same samples. Conclusion: Our results clearly demonstrate that mouse and human contactin-2 are physiological substrates for BACE1. BACE1-mediated contactin-2 cleavage tightly regulates the surface expression of contactin-2 in neuronal cells. Given the role of contactin-2 in cell adhesion, neurite outgrowth and axon guidance, our data suggest that BACE1 may play an important role in these physiological processes by regulating contactin-2 surface levels
A search for the near-infrared counterpart of the eclipsing millisecond X-ray pulsar Swift J1749.4-2807
Swift J1749.4-2807 is a transient accreting millisecond X-ray pulsars, the
first that displayed X-ray eclipses. Therefore it holds a great potential for
accurate mass measurements in a low mass X-ray binary system. The determination
of the companion star radial velocity would make it possible to fully resolve
the system and to accurately measure the mass of the neutron star based on
dynamical measurements. Unfortunately, no optical/NIR counterpart has been
identified to date for this system, either in outburst or in quiescence. We
performed a photometric study of the field of Swift J1749.4-2807 during
quiescence in order to search for the presence of a variable counterpart. The
source direction lies on the Galactic plane, making any search for its
optical/NIR counterpart challenging. To minimize the effects of field crowding
and interstellar extinction, we carried out our observations using the adaptive
optics near-infrared imager NACO mounted at the ESO Very Large Telescope. From
the analysis of Swift X-ray data obtained during outburst, we derived the most
precise (1.6" radius) position for this source. Due to the extreme stellar
crowding of the field, 41 sources are detected in our VLT images within the
X-ray error circle, with some of them possibly showing variability consistent
with the expectations. We carried out the first deep imaging campaign devoted
to the search of the quiescent NIR counterpart of Swift J1749.4-2807. Our
results allow to provide constraints on the nature of the companion star of
this system. Furthermore, they suggest that future phase-resolved NIR
observations (performed with large aperture telescopes and adaptive optics)
covering the full orbital period of the system are likely to identify the
quiescent counterpart of Swift J1749.4-2807, through the measure of its orbital
variability, opening the possibility of dynamical studies of this unique
source.Comment: 5 pages, 3 figures, accepted for publication in Astronomy and
Astrophysic
A novel CRISPR/Cas9-based iduronate-2-sulfatase (IDS) knockout human neuronal cell line reveals earliest pathological changes
Multiple complex intracellular cascades contributing to Hunter syndrome (mucopolysaccharidosis type II) pathogenesis have been recognized and documented in the past years. However, the hierarchy of early cellular abnormalities leading to irreversible neuronal damage is far from being completely understood. To tackle this issue, we have generated two novel iduronate-2-sulfatase (IDS) loss of function human neuronal cell lines by means of genome editing. We show that both neuronal cell lines exhibit no enzymatic activity and increased GAG storage despite a completely different genotype. At a cellular level, they display reduced differentiation, significantly decreased LAMP1 and RAB7 protein levels, impaired lysosomal acidification and increased lipid storage. Moreover, one of the two clones is characterized by a marked decrease of the autophagic marker p62, while none of the two mutants exhibit marked oxidative stress and mitochondrial morphological changes. Based on our preliminary findings, we hypothesize that neuronal differentiation might be significantly affected by IDS functional impairment
From Classical Trajectories to Quantum Commutation Relations
In describing a dynamical system, the greatest part of the work for a
theoretician is to translate experimental data into differential equations. It
is desirable for such differential equations to admit a Lagrangian and/or an
Hamiltonian description because of the Noether theorem and because they are the
starting point for the quantization. As a matter of fact many ambiguities arise
in each step of such a reconstruction which must be solved by the ingenuity of
the theoretician. In the present work we describe geometric structures emerging
in Lagrangian, Hamiltonian and Quantum description of a dynamical system
underlining how many of them are not really fixed only by the trajectories
observed by the experimentalist.Comment: 25 pages. Comments are welcome
Simultaneous multiwavelength observations of the Low/Hard State of the X-ray transient source SWIFT J1753.5-0127
We report the results of simultaneous multiwavelength observations of the
X-ray transient source SWIFT J1753.5-0127 performed with INTEGRAL, RXTE, NTT,
REM and VLA on 2005 August 10-12. The source, which underwent an X-ray outburst
since 2005 May 30, was observed during the INTEGRAL Target of Opportunity
program dedicated to new X-ray novae located in the Galactic Halo. Broad-band
spectra and fast timing variability properties of SWIFT J1753.5-0127 are
analyzed together with the optical, near infra-red and radio data. We show that
the source was significantly detected up to 600 keV with Comptonization
parameters and timing properties typical of the so-called Low/Hard State of
black hole candidates. We build a spectral energy distribution and we show that
SWIFT J1753.5-0127 does not follow the usual radio/X-ray correlation of X-ray
binaries in the Low/Hard State. We give estimates of distance and mass. We
conclude that SWIFT J1753.5-0127 belongs to the X-ray nova class and that it is
likely a black hole candidate transient source of the Galactic Halo which
remained in the Low/Hard State during its main outburst. We discuss our results
within the context of Comptonization and jet models.Comment: Accepted for publication in ApJ, 25 pages, 4 tables, 11 figures (3 in
color
Stopping of Charged Particles in a Magnetized Classical Plasma
The analytical and numerical investigations of the energy loss rate of the
test particle in a magnetized electron plasma are developed on the basis of the
Vlasov-Poisson equations, and the main results are presented. The Larmor
rotation of a test particle in a magnetic field is taken into account. The
analysis is based on the assumption that the energy variation of the test
particle is much less than its kinetic energy. The obtained general expression
for stopping power is analyzed for three cases: (i) the particle moves through
a collisionless plasma in a strong homogeneous magnetic field; (ii) the fast
particle moves through a magnetized collisionless plasma along the magnetic
field; and (iii) the particle moves through a magnetized collisional plasma
across a magnetic field. Calculations are carried out for the arbitrary test
particle velocities in the first case, and for fast particles in the second and
third cases. It is shown that the rate at which a fast test particle loses
energy while moving across a magnetic field may be much higher than the loss in
the case of motion through plasma without magnetic field.Comment: 14 pages, 3 figures, LaTe
SN 2013dx associated with GRB 130702A: a detailed photometric and spectroscopic monitoring and a study of the environment
Long duration gamma-ray bursts (GRBs) and broad-line, type Ic supernovae (SNe) are strongly connected. We aim at characterizing SN 2013dx, associated with GRB\,130702A, through sensitive and extensive ground-based observational campaigns in the optical-IR band. We monitored the field of the Swift GRB 130702A (redshift z = 0.145) using the 8.2-m VLT, the 3.6-m TNG and the 0.6-m REM telescopes during the time interval between 4 and 40 days after the burst. Photometric and spectroscopic observations revealed the presence of the associated Type Ic SN 2013dx. Our multi-band photometry allowed the construction of a bolometric light curve.} The bolometric light curve of SN 2013dx resembles that of 2003dh (associated with GRB 030329), but is ~10% faster and ~25% dimmer. From this we infer a synthesized 56Ni mass of ~0.2 solar masses. The multi-epoch optical spectroscopy shows that the SN 2013dx behavior is best matched by SN 1998bw, among the other well-known low-redshift SNe associated with GRBs and XRFs, and by SN 2010ah, an energetic Type Ic SN not associated with any GRB. The photospheric velocity of the ejected material declines from ~2.7X10^4 km/s at 8 rest frame days from the explosion, to ~3.5X10^3 km/s at 40 days. These values are extremely close to those of SN1998bw and 2010ah. We deduce for SN 2013dx a kinetic energy of ~35X10^51 erg, and an ejected mass of ~7 solar masses. This suggests that the progenitor of SN2013dx had a mass of ~25 solar masses, i.e., 15-20% less massive than that of SN 1998bw. Finally, we performed a study of the SN 2013dx environment, through spectroscopy of the closeby galaxies. 9 out of the 14 inspected galaxies lie within 0.03 in redshift from z=0.145, indicating that the host of GRB 130702A/SN 2013dx belongs to a group of galaxies, an unprecedented finding for a GRB-associated SN and, to our knowledge, for long GRBs in general
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