10,945 research outputs found
Micro-bias and macro-performance
We use agent-based modeling to investigate the effect of conservatism and
partisanship on the efficiency with which large populations solve the density
classification task--a paradigmatic problem for information aggregation and
consensus building. We find that conservative agents enhance the populations'
ability to efficiently solve the density classification task despite large
levels of noise in the system. In contrast, we find that the presence of even a
small fraction of partisans holding the minority position will result in
deadlock or a consensus on an incorrect answer. Our results provide a possible
explanation for the emergence of conservatism and suggest that even low levels
of partisanship can lead to significant social costs.Comment: 11 pages, 5 figure
Plasma membrane-specific interactome analysis reveals calpain 1 as a druggable modulator of rescued Phe508del-CFTR cell surface stability
Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding CF transmembrane conductance regulator (CFTR), a chloride channel normally expressed at the surface of epithelial cells. The most frequent mutation, resulting in Phe-508 deletion, causes CFTR misfolding and its premature degradation. Low temperature or pharmacological correctors can partly rescue the Phe508del-CFTR processing defect and enhance trafficking of this channel variant to the plasma membrane (PM). Nevertheless, the rescued channels have an increased endocytosis rate, being quickly removed from the PM by the peripheral protein quality-control pathway. We previously reported that rescued Phe508del-CFTR (rPhe508del) can be retained at the cell surface by stimulating signaling pathways that coax the adaptor molecule ezrin (EZR) to tether rPhe508delâNa+/H+-exchange regulatory factor-1 (NHERF1) complexes to the actin cytoskeleton, thereby averting the rapid internalization of this channel variant. However, the molecular basis for why rPhe508del fails to recruit active EZR to the PM remains elusive. Here, using a proteomics approach, we characterized and compared the core components of wt-CFTRâ or rPhe508delâcontaining macromolecular complexes at the surface of human bronchial epithelial cells. We identified calpain 1 (CAPN1) as an exclusive rPhe508del interactor that prevents active EZR recruitment, impairs rPhe508del anchoring to actin, and reduces its stability in the PM. We show that either CAPN1 downregulation or its chemical inhibition dramatically improves the functional rescue of Phe508del-CFTR in airway cells. These observations suggest that CAPN1 constitutes an attractive target for pharmacological intervention, as part of CF combination therapies restoring Phe508del-CFTR function.This work was supported by a center grant UID/MULTI/04046/2019
to BioISI and project PTDC/BIA-CEL/28408/2017 and IF2012 to PM,
both from FCT, Portugal. AMM was recipient of fellowship
SFRH/BD/52490/2014 from BioSYS PhD programme PD65-2012,
and PB of fellowship SFRH/BPD/94322/2013.N/
Orbital Characteristics of the Subdwarf-B and F V Star Binary EC~20117-4014(=V4640 Sgr)
Among the competing evolution theories for subdwarf-B (sdB) stars is the
binary evolution scenario. EC~20117-4014 (=V4640~Sgr) is a spectroscopic binary
system consisting of a pulsating sdB star and a late F main-sequence companion
(O'Donoghue et al. 1997), however the period and the orbit semi-major axes have
not been precisely determined. This paper presents orbital characteristics of
the EC 20117-4014 binary system using 20 years of photometric data. Periodic
Observed minus Calculated (O-C) variations were detected in the two highest
amplitude pulsations identified in the EC 20117-4014 power spectrum, indicating
the binary system's precise orbital period (P = 792.3 days) and the
light-travel time amplitude (A = 468.9 s). This binary shows no significant
orbital eccentricity and the upper limit of the eccentricity is 0.025 (using 3
as an upper limit). This upper limit of the eccentricity is the lowest
among all wide sdB binaries with known orbital parameters. This analysis
indicated that the sdB is likely to have lost its hydrogen envelope through
stable Roche lobe overflow, thus supporting hypotheses for the origin of sdB
stars. In addition to those results, the underlying pulsation period change
obtained from the photometric data was = 5.4 (0.7)
d d, which shows that the sdB is just before the end of the
core helium-burning phase
Ice Age Epochs and the Sun's Path Through the Galaxy
We present a calculation of the Sun's motion through the Milky Way Galaxy
over the last 500 million years. The integration is based upon estimates of the
Sun's current position and speed from measurements with Hipparcos and upon a
realistic model for the Galactic gravitational potential. We estimate the times
of the Sun's past spiral arm crossings for a range in assumed values of the
spiral pattern angular speed. We find that for a difference between the mean
solar and pattern speed of Omega_Sun - Omega_p = 11.9 +/- 0.7 km/s/kpc the Sun
has traversed four spiral arms at times that appear to correspond well with
long duration cold periods on Earth. This supports the idea that extended
exposure to the higher cosmic ray flux associated with spiral arms can lead to
increased cloud cover and long ice age epochs on Earth.Comment: 14 pages, 3 figures, accepted for publication in Ap
Hilbert Space of Isomorphic Representations of Bosonized Chiral
We analyse the Hilbert space structure of the isomorphic gauge non-invariant
and gauge invariant bosonized formulations of chiral for the particular
case of the Jackiw-Rajaraman parameter . The BRST subsidiary conditions
are found not to provide a sufficient criterium for defining physical states in
the Hilbert space and additional superselection rules must to be taken into
account. We examine the effect of the use of a redundant field algebra in
deriving basic properties of the model. We also discuss the constraint
structure of the gauge invariant formulation and show that the only primary
constraints are of first class.Comment: LaTeX, 19 page
On Universality in Human Correspondence Activity
Identifying and modeling patterns of human activity has important
ramifications in applications ranging from predicting disease spread to
optimizing resource allocation. Because of its relevance and availability,
written correspondence provides a powerful proxy for studying human activity.
One school of thought is that human correspondence is driven by responses to
received correspondence, a view that requires distinct response mechanism to
explain e-mail and letter correspondence observations. Here, we demonstrate
that, like e-mail correspondence, the letter correspondence patterns of 16
writers, performers, politicians, and scientists are well-described by the
circadian cycle, task repetition and changing communication needs. We confirm
the universality of these mechanisms by properly rescaling letter and e-mail
correspondence statistics to reveal their underlying similarity.Comment: 17 pages, 3 figures, 1 tabl
Dynamics of Rumor Spreading in Complex Networks
We derive the mean-field equations characterizing the dynamics of a rumor
process that takes place on top of complex heterogeneous networks. These
equations are solved numerically by means of a stochastic approach. First, we
present analytical and Monte Carlo calculations for homogeneous networks and
compare the results with those obtained by the numerical method. Then, we study
the spreading process in detail for random scale-free networks. The time
profiles for several quantities are numerically computed, which allow us to
distinguish among different variants of rumor spreading algorithms. Our
conclusions are directed to possible applications in replicated database
maintenance, peer to peer communication networks and social spreading
phenomena.Comment: Final version to appear in PR
A new picture on (3+1)D topological mass mechanism
We present a class of mappings between the fields of the Cremmer-Sherk and
pure BF models in 4D. These mappings are established by two distinct
procedures. First a mapping of their actions is produced iteratively resulting
in an expansion of the fields of one model in terms of progressively higher
derivatives of the other model fields. Secondly an exact mapping is introduced
by mapping their quantum correlation functions. The equivalence of both
procedures is shown by resorting to the invariance under field scale
transformations of the topological action. Related equivalences in 5D and 3D
are discussed. A cohomological argument is presented to provide consistency of
the iterative mapping.Comment: 13 page
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