Hierarchically-coupled hidden Markov models for learning kinetic rates from single-molecule data

We address the problem of analyzing sets of noisy time-varying signals that all report on the same process but confound straightforward analyses due to complex inter-signal heterogeneities and measurement artifacts. In particular we consider single-molecule experiments which indirectly measure the distinct steps in a biomolecular process via observations of noisy time-dependent signals such as a fluorescence intensity or bead position. Straightforward hidden Markov model (HMM) analyses attempt to characterize such processes in terms of a set of conformational states, the transitions that can occur between these states, and the associated rates at which those transitions occur; but require ad-hoc post-processing steps to combine multiple signals. Here we develop a hierarchically coupled HMM that allows experimentalists to deal with inter-signal variability in a principled and automatic way. Our approach is a generalized expectation maximization hyperparameter point estimation procedure with variational Bayes at the level of individual time series that learns an single interpretable representation of the overall data generating process.Comment: 9 pages, 5 figure

Musical Training Enhances Inhibitory Control in Adolescence

Music production is a complex activity that involves nearly every function in the brain. Whether skills transfer from musical training to other cognitive abilities is a growing area of research. There is evidence to suggest that musical training in children and adult musicians is associated with an improvement in a variety of executive functions (EFs). This study examined whether those associations are also present during adolescence, and whether there is a relationship between the time spent in musical training and EF. Adolescents between the ages of 14 and 18 completed three tests of EF: Tower of Hanoi to assess working memory, Wisconsin Card Sort Test to assess cognitive flexibility, and Stroop Color Word Task to assess inhibition. They also completed a musical experience questionnaire, including their lifetime musical practice hours. Adolescent musicians were found to have improved inhibitory control (as measured by the Stroop Task) relative to nonmusicians and inhibition correlated with musical practice time. No other elements of EF were found to be associated with musical training. These findings suggest that the impact of musical training may not be the same for all EFs, and that there may be unique associations between this type of training and inhibitory control

Tuning quantum non-local effects in graphene plasmonics

The response of an electron system to electromagnetic fields with sharp spatial variations is strongly dependent on quantum electronic properties, even in ambient conditions, but difficult to access experimentally. We use propagating graphene plasmons, together with an engineered dielectric-metallic environment, to probe the graphene electron liquid and unveil its detailed electronic response at short wavelengths.The near-field imaging experiments reveal a parameter-free match with the full theoretical quantum description of the massless Dirac electron gas, in which we identify three types of quantum effects as keys to understanding the experimental response of graphene to short-ranged terahertz electric fields. The first type is of single-particle nature and is related to shape deformations of the Fermi surface during a plasmon oscillations. The second and third types are a many-body effect controlled by the inertia and compressibility of the interacting electron liquid in graphene. We demonstrate how, in principle, our experimental approach can determine the full spatiotemporal response of an electron system.Comment: 8 pages, 4 figure

Numerical Modeling of Eta Carinae Bipolar Outflows

In this paper, we present two-dimensional gas dynamic simulations of the formation and evolution of the eta-Car bipolar outflows. Adopting the interacting nonspherical winds model, we have carried out high-resolution numerical simulations, which include explicitly computed time-dependent radiative cooling, for different possible scenarios of the colliding winds. In our simulations, we consider different degrees of non-spherical symmetry for the pre-outburst wind and the great eruption of the 1840s presented by the eta-Car wind. From these models, we obtain important differences in the shape and kinematical properties of the Homunculus structure. In particular, we find an appropriate combination of the wind parameters (that control the degree of non-spherical symmetry) and obtain numerical experiments that best match both the observed morphology and the expansion velocity of the eta-Car bipolar shell. In addition, our numerical simulations show the formation of a bipolar nebula embedded within the Homunculus (the little Homunculus) developed from a secondary eruptive event suffered by the star in the 1890s, and also the development of tenuous, high velocity ejections in the equatorial region that result from the impact of the eruptive wind of the 1840s with the pre-outburst wind and that could explain some of the high speed features observed in the equatorial ejecta. The models were, however, unable to produce equatorial ejections associated to the second eruptive event.Comment: 33 pages, 9 figures, accepted by the Astrophysical Journa

Optical Monitoring of the Broad-Line Radio Galaxy 3C390.3

We have undertaken a new ground-based monitoring campaign on the BLRG 3C390.3 to improve the measurement of the size of the BLR and to estimate the black hole mass. Optical spectra and g-band images were observed in 2005 using the 2.4m telescope at MDM Observatory. Integrated emission-line flux variations were measured for Ha, Hb, Hg, and for HeII4686, as well as g-band fluxes and the optical AGN continuum at 5100A. The g-band fluxes and the AGN continuum vary simultaneously within the uncertainties, tau=(0.2+-1.1)days. We find that the emission-line variations are delayed with respect to the variable g-band continuum by tau(Ha)=56.3(+2.4-6.6)days, tau(Hb)=44.3(+3.0_-3.3)days, tau(Hg)=58.1(+4.3-6.1)days, and tau(HeII4686)=22.3(+6.5-3.8)days. The blue and red peak in the double peaked line profiles, as well as the blue and red outer profile wings, vary simultaneously within +-3 days. This provides strong support for gravitationally bound orbital motion of the dominant part of the line emitting gas. Combining the time delay of Ha and Hb and the separation of the blue and red peak in the broad double-peaked profiles in their rms spectra, we determine Mbh_vir=1.77(+0.29-0.31)x10^8Msol and using sigma_line of the rms spectra Mbh_vir=2.60(+0.23-0.31)x10^8Msol for the central black hole of 3C390.3, respectively. Using the inclination angle of the line emitting region the mass of the black hole amounts to Mbh=0.86(+0.19-0.18)x10^9 Msol (peak-separation) and Mbh=1.26(+0.21-0.16)x10^9 Msol (sigma_line), respectively. This result is consistent with the black hole masses indicated by simple accretion disk models to describe the observed double-peaked profiles, derived from the stellar dynamics of 3C390.3, and with the AGN radius-luminosity relation. Thus, 3C390.3 as a radio-loud AGN with a low Eddington ratio, Ledd/Lbol=0.02, follows the same AGN radius-luminosity relation as radio-quiet AGN.Comment: accepted, scheduled for September 20, 2012, ApJ 75

Development and clinical performance of high throughput loop-mediated isothermal amplification for detection of malaria.

BACKGROUND: Accurate and efficient detection of sub-microscopic malaria infections is crucial for enabling rapid treatment and interruption of transmission. Commercially available malaria LAMP kits have excellent diagnostic performance, though throughput is limited by the need to prepare samples individually. Here, we evaluate the clinical performance of a newly developed high throughput (HTP) sample processing system for use in conjunction with the Eiken malaria LAMP kit. METHODS: The HTP system utilised dried blood spots (DBS) and liquid whole blood (WB), with parallel sample processing of 94 samples per run. The system was evaluated using 699 samples of known infection status pre-determined by gold standard nested PCR. RESULTS: The sensitivity and specificity of WB-HTP-LAMP was 98.6% (95% CI, 95.7-100), and 99.7% (95% CI, 99.2-100); sensitivity of DBS-HTP-LAMP was 97.1% (95% CI, 93.1-100), and specificity 100% against PCR. At parasite densities greater or equal to 2 parasites/μL, WB and DBS HTP-LAMP showed 100% sensitivity and specificity against PCR. At densities less than 2 p/μL, WB-HTP-LAMP sensitivity was 88.9% (95% CI, 77.1-100) and specificity was 99.7% (95% CI, 99.2-100); sensitivity and specificity of DBS-HTP-LAMP was 77.8% (95% CI, 54.3-99.5) and 100% respectively. CONCLUSIONS: The HTP-LAMP system is a highly sensitive diagnostic test, with the potential to allow large scale population screening in malaria elimination campaigns