5,156 research outputs found
The dynamics of public opinion under majority rules
This note explains the process of public opinion formation via a locally interactive, space-time analysis. The model we use is a special case of the general framework for modelling social interaction proposed in Blume and Durlauf (2001). In the reduced form of the model we study how each individual, when faced with the choice of one, out of two, opinions, tends to conform to the opinion held by the majority of her neighbours. We consider different, symmetric and asymmetric, majority rules. Depending on the specific behavioral rule, the aggregate process of opinion formation may display contagion on one specific opinion, or consensus among all individuals in the population, or co-existence of both opinions. Whenever consensus obtains, we observe the formation of homogeneous areas (clusters) that seem almost stationary along the dynamics
Cystic fibrosis transmembrane conductance regulator (CFTR): closed and open state channel models.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the ATP binding cassette (ABC) transporter superfamily. CFTR controls the flow of anions through the apical membrane of epithelia. Dysfunctional CFTR causes the common lethal genetic disease cystic fibrosis. Transitions between open and closed states of CFTR are regulated by ATP binding and hydrolysis on the cystosolic nucleotide binding domains (NBDs), which are coupled with the transmembrane domains (TMDs) forming the pathway for anion permeation. Lack of structural data hampers a global understanding of CFTR, and thus the development of rational approaches directly targeting defective CFTR. In this work, we explored possible conformational states of the CFTR gating cycle by means of homology modeling. As templates, we used structures of homologous ABC transporters, namely TM287- 288, ABC-B10, McjD and Sav1866. In the light of published experimental results, structural analysis of the transmembrane cavity suggests that the TM287-288-based CFTR model could correspond to a commonly occupied closed state, while the McjD-based model could represent an open state. The models capture the important role played by Phe337 as a filter/gating residue and provide structural information on the conformational transition from closed to open channel
Structure of Transmembrane Helix 8 and Possible Membrane Defects in CFTR
The cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel that regulates the flow of anions across epithelia. Mutations in CFTR cause cystic fibrosis. CFTR belongs to the ATP-binding cassette transporter superfamily, and gating is controlled by phosphorylation and ATP binding and hydrolysis. Recently obtained ATP-free and ATP-bound structures of zebrafish CFTR revealed an unwound segment of transmembrane helix (TM) 8, which appears to be a unique feature of CFTR not present in other ATP-binding cassette transporter structures. Here, using ÎŒs-long molecular dynamics simulations, we investigate the interactions formed by this TM8 segment with nearby helices in both ATP-free and ATP-bound states. We highlight ATP-dependent interactions as well as the structural role of TM8 in maintaining the functional architecture of the pore via interactions common to both the ATP-bound and ATP-free state. The results of the molecular dynamics simulations are discussed in the context of the gating mechanism of CFTR
Real-time prediction with U.K. monetary aggregates in the presence of model uncertainty
A popular account for the demise of the U.K.âs monetary targeting regime in the 1980s blames the fluctuating predictive relationships between broad money and inflation and real output growth. Yet ex post policy analysis based on heavily revised data suggests no fluctuations in the predictive content of money. In this paper, we investigate the predictive relationships for inflation and output growth using both real-time and heavily revised data. We consider a large set of recursively estimated vector autoregressive (VAR) and vector error correction models (VECM). These models differ in terms of lag length and the number of cointegrating relationships. We use Bayesian model averaging (BMA) to demonstrate that real-time monetary policymakers faced considerable model uncertainty. The in-sample predictive content of money fluctuated during the 1980s as a result of data revisions in the presence of model uncertainty. This feature is only apparent with real-time data as heavily revised data obscure these fluctuations. Out-of-sample predictive evaluations rarely suggest that money matters for either inflation or real output. We conclude that both data revisions and model uncertainty contributed to the demise of the U.K.âs monetary targeting regime
Can two wrongs make a right? F508del-CFTR ion channel rescue by second-site mutations in its transmembrane domains
Deletion of phenylalanine 508 (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel is the most common cause of cystic fibrosis (CF). The F508 residue is located on nucleotide-binding domain 1 (NBD1) in contact with the cytosolic extensions of the transmembrane helices, in particular intracellular loop 4 (ICL4). To investigate how absence of F508 at this interface impacts the CFTR protein, we carried out a mutagenesis scan of ICL4 by introducing second-site mutations at eleven positions in cis with F508del. Using an image-based fluorescence assay, we measured how each mutation affected membrane proximity and ion-channel function. The scan strongly validated the effectiveness of R1070W at rescuing F508del defects. Molecular dynamics simulations highlighted two features characterizing the ICL4/NBD1 interface of F508del/R1070W-CFTR: flexibility, with frequent transient formation of interdomain hydrogen bonds, and loosely stacked aromatic sidechains (F1068, R1070W, and F1074, mimicking F1068, F508 and F1074 in wild-type CFTR). F508del-CFTR displayed a distorted aromatic stack, with F1068 displaced towards the space vacated by F508, while, in F508del/R1070F-CFTR, which largely retained F508del defects, R1070F could not form hydrogen bonds and the interface was less flexible. Other ICL4 second-site mutations which partially rescued F508del-CFTR included F1068M and F1074M. Methionine side chains allow hydrophobic interactions without the steric rigidity of aromatic rings, possibly conferring flexibility to accommodate the absence of F508 and retain a dynamic interface. These studies highlight how both hydrophobic interactions and conformational flexibility might be important at the ICL4/NBD1 interface, suggesting possible structural underpinnings of F508del-induced dysfunction
CHANTI: a Fast and Efficient Charged Particle Veto Detector for the NA62 Experiment at CERN
The design, construction and test of a charged particle detector made of
scintillation counters read by Silicon Photomultipliers (SiPM) is described.
The detector, which operates in vacuum and is used as a veto counter in the
NA62 experiment at CERN, has a single channel time resolution of 1.14 ns, a
spatial resolution of ~2.5 mm and an efficiency very close to 1 for penetrating
charged particles
Mobile Cloud Support for Semantic-Enriched Speech Recognition in Social Care
Nowadays, most users carry high computing power mobile devices where speech recognition is certainly one of the main technologies available in every modern smartphone, although battery draining and application performance (resource shortage) have a big impact on the experienced quality. Shifting applications and services to the cloud may help to improve mobile user satisfaction as demonstrated by several ongoing efforts in the mobile cloud area. However, the quality of speech recognition is still not sufficient in many complex cases to replace the common hand written text, especially when prompt reaction to short-term provisioning requests is required. To address the new scenario, this paper proposes a mobile cloud infrastructure to support the extraction of semantics information from speech recognition in the Social Care domain, where carers have to speak about their patients conditions in order to have reliable notes used afterward to plan the best support. We present not only an architecture proposal, but also a real prototype that we have deployed and thoroughly assessed with different queries, accents, and in presence of load peaks, in our experimental mobile cloud Platform as a Service (PaaS) testbed based on Cloud Foundry
MHD Stellar and Disk Winds: Application to Planetary Nebulae
MHD winds can emanate from both stars and surrounding accretion disks. It is
of interest to know how much wind power is available and which (if either) of
the two rotators dominates that power. We investigate this in the context of
multi-polar planetary nebulae (PNe) and proto-planetary nebulae (PPNe), for
which recent observations have revealed the need for a wind power source in
excess of that available from radiation driving, and a possible need for
magnetic shaping. We calculate the MHD wind power from a coupled disk and star,
where the former results from binary disruption. The resulting wind powers
depend only on the accretion rate and stellar properties. We find that if the
stellar envelope were initially slowly rotating, the disk wind would dominate
throughout the evolution. If the envelope of the star were rapidly rotating,
the stellar wind could initially be of comparable power to the disk wind until
the stellar wind carries away the star's angular momentum. Since an initially
rapidly rotating star can have its spin and magnetic axes misaligned to the
disk, multi-polar outflows can result from this disk wind system. For times
greater than a spin-down time, the post-AGB stellar wind is slaved to the disk
for both slow and rapid initial spin cases and the disk wind luminosity
dominates. We find a reasonably large parameter space where a hybrid star+disk
MHD driven wind is plausible and where both or either can account for PPNe and
PNe powers. We also speculate on the morphologies which may emerge from the
coupled system. The coupled winds might help explain the shapes of a number of
remarkable multi-shell or multi-polar nebulae. Magnetic activity such as X-ray
flares may be associated with the both central star and the disk and would be a
valuable diagnostic for the dynamical role of MHD processes in PNe.Comment: ApJ accepted version, incorporating some important revisions. 25
Pages, LaTex, + 5 fig
VITRUV - Science Cases
VITRUV is a second generation spectro-imager for the PRIMA enabled Very Large
Telescope Interferometer. By combining simultaneously up to 8 telescopes VITRUV
makes the VLTI up to 6 times more efficient. This operational gain allows two
novel scientific methodologies: 1) massive surveys of sizes; 2) routine
interferometric imaging. The science cases presented concentrate on the
qualitatively new routine interferometric imaging methodology. The science
cases are not exhaustive but complementary to the PRIMA reference mission. The
focus is on: a) the close environment of young stars probing for the initial
conditions of planet formation and disk evolution; b) the surfaces of stars
tackling dynamos, activity, pulsation, mass-loss and evolution; c) revealing
the origin of the extraordinary morphologies of Planetary Nebulae and related
stars; d) studying the accretion-ejection structures of stellar black-holes
(microquasars) in our galaxy; e) unveiling the different interacting components
(torus, jets, BLRs) of Active Galactic Nuclei; and f) probing the environment
of nearby supermassive black-holes and relativistic effects in the Galactic
Center black-hole.Comment: 15 pages. The Power of Optical/IR Interferometry: Recent Scientific
Results and 2nd Generation VLTI Instrumentation, Allemagne (2005) in pres
Energy and time resolution for a LYSO matrix prototype of the Mu2e experiment
We have measured the performances of a LYSO crystal matrix prototype tested
with electron and photon beams in the energy range 60450 MeV. This study has
been carried out to determine the achievable energy and time resolutions for
the calorimeter of the Mu2e experiment.Comment: 2 pages, 3 figures, 13th Pisa Meeting on Advanced Detector
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