655 research outputs found
Inferring hidden Markov models from noisy time sequences: a method to alleviate degeneracy in molecular dynamics
We present a new method for inferring hidden Markov models from noisy time
sequences without the necessity of assuming a model architecture, thus allowing
for the detection of degenerate states. This is based on the statistical
prediction techniques developed by Crutchfield et al., and generates so called
causal state models, equivalent to hidden Markov models. This method is
applicable to any continuous data which clusters around discrete values and
exhibits multiple transitions between these values such as tethered particle
motion data or Fluorescence Resonance Energy Transfer (FRET) spectra. The
algorithms developed have been shown to perform well on simulated data,
demonstrating the ability to recover the model used to generate the data under
high noise, sparse data conditions and the ability to infer the existence of
degenerate states. They have also been applied to new experimental FRET data of
Holliday Junction dynamics, extracting the expected two state model and
providing values for the transition rates in good agreement with previous
results and with results obtained using existing maximum likelihood based
methods.Comment: 19 pages, 9 figure
Energy Extraction from Spinning Black Holes via Relativistic Jets
It has for long been an article of faith among astrophysicists that black
hole spin energy is responsible for powering the relativistic jets seen in
accreting black holes. Two recent advances have strengthened the case. First,
numerical general relativistic magnetohydrodynamic simulations of accreting
spinning black holes show that relativistic jets form spontaneously. In at
least some cases, there is unambiguous evidence that much of the jet energy
comes from the black hole, not the disk. Second, spin parameters of a number of
accreting stellar-mass black holes have been measured. For ballistic jets from
these systems, it is found that the radio luminosity of the jet correlates with
the spin of the black hole. This suggests a causal relationship between black
hole spin and jet power, presumably due to a generalized Penrose process.Comment: 15 pages, 4 figures. To appear in the proceedings of the conference
"Relativity and Gravitation: 100 Years after Einstein in Prague" held in
Prague, June 25-29, 2012, Ji\v{r}\'i Bi\v{c}\'ak and Tom\'a\v{s} Ledvinka
editors, Max-Planck Research Library for the History and Development of
Knowledge, Open Access Edition, Berlin (2013
Molecular Valves for Controlling Gas Phase Transport Made from Discrete Angstrom-Sized Pores in Graphene
An ability to precisely regulate the quantity and location of molecular flux
is of value in applications such as nanoscale 3D printing, catalysis, and
sensor design. Barrier materials containing pores with molecular dimensions
have previously been used to manipulate molecular compositions in the gas
phase, but have so far been unable to offer controlled gas transport through
individual pores. Here, we show that gas flux through discrete angstrom-sized
pores in monolayer graphene can be detected and then controlled using
nanometer-sized gold clusters, which are formed on the surface of the graphene
and can migrate and partially block a pore. In samples without gold clusters,
we observe stochastic switching of the magnitude of the gas permeance, which we
attribute to molecular rearrangements of the pore. Our molecular valves could
be used, for example, to develop unique approaches to molecular synthesis that
are based on the controllable switching of a molecular gas flux, reminiscent of
ion channels in biological cell membranes and solid state nanopores.Comment: to appear in Nature Nanotechnolog
Transcriptional characterization of human megakaryocyte polyploidization and lineage commitment
BACKGROUND: Megakaryocytes (MKs) originate from cells immuno-phenotypically indistinguishable from hematopoietic stem cells (HSCs), bypassing intermediate progenitors. They mature within the adult bone marrow and release platelets into the circulation. Until now, there have been no transcriptional studies of primary human bone marrow MKs. OBJECTIVES: To characterize MKs and HSCs from human bone marrow using single-cell RNA sequencing, to investigate MK lineage commitment, maturation steps, and thrombopoiesis. RESULTS: We show that MKs at different levels of polyploidization exhibit distinct transcriptional states. Although high levels of platelet-specific gene expression occur in the lower ploidy classes, as polyploidization increases, gene expression is redirected toward translation and posttranslational processing transcriptional programs, in preparation for thrombopoiesis. Our findings are in keeping with studies of MK ultrastructure and supersede evidence generated using in vitro cultured MKs. Additionally, by analyzing transcriptional signatures of a single HSC, we identify two MK-biased HSC subpopulations exhibiting unique differentiation kinetics. We show that human bone marrow MKs originate from these HSC subpopulations, supporting the notion that they display priming for MK differentiation. Finally, to investigate transcriptional changes in MKs associated with stress thrombopoiesis, we analyzed bone marrow MKs from individuals with recent myocardial infarction and found a specific gene expression signature. Our data support the modulation of MK differentiation in this thrombotic state. CONCLUSIONS: Here, we use single-cell sequencing for the first time to characterize the human bone marrow MK transcriptome at different levels of polyploidization and investigate their differentiation from the HSC
Bright ligand-activatable fluorescent protein for high-quality multicolor live-cell super-resolution microscopy
We introduce UnaG as a green-to-dark photoswitching fluorescent protein capable of high-quality super-resolution imaging with photon numbers equivalent to the brightest photoswitchable red protein. UnaG only fluoresces upon binding of a fluorogenic metabolite, bilirubin, enabling UV-free reversible photoswitching with easily controllable kinetics and low background under Epi illumination. The on- and off-switching rates are controlled by the concentration of the ligand and the excitation light intensity, respectively, where the dissolved oxygen also promotes the off-switching. The photo-oxidation reaction mechanism of bilirubin in UnaG suggests that the lack of ligand-protein covalent bond allows the oxidized ligand to detach from the protein, emptying the binding cavity for rebinding to a fresh ligand molecule. We demonstrate super-resolution single-molecule localization imaging of various subcellular structures genetically encoded with UnaG, which enables facile labeling and simultaneous multicolor imaging of live cells. UnaG has the promise of becoming a default protein for high-performance super-resolution imaging. Photoconvertible proteins occupy two color channels thereby limiting multicolour localisation microscopy applications. Here the authors present UnaG, a new green-to-dark photoswitching fluorescent protein for super-resolution imaging, whose activation is based on a noncovalent binding with bilirubin
Foundations of Black Hole Accretion Disk Theory
This review covers the main aspects of black hole accretion disk theory. We
begin with the view that one of the main goals of the theory is to better
understand the nature of black holes themselves. In this light we discuss how
accretion disks might reveal some of the unique signatures of strong gravity:
the event horizon, the innermost stable circular orbit, and the ergosphere. We
then review, from a first-principles perspective, the physical processes at
play in accretion disks. This leads us to the four primary accretion disk
models that we review: Polish doughnuts (thick disks), Shakura-Sunyaev (thin)
disks, slim disks, and advection-dominated accretion flows (ADAFs). After
presenting the models we discuss issues of stability, oscillations, and jets.
Following our review of the analytic work, we take a parallel approach in
reviewing numerical studies of black hole accretion disks. We finish with a few
select applications that highlight particular astrophysical applications:
measurements of black hole mass and spin, black hole vs. neutron star accretion
disks, black hole accretion disk spectral states, and quasi-periodic
oscillations (QPOs).Comment: 91 pages, 23 figures, final published version available at
http://www.livingreviews.org/lrr-2013-
Association of early life factors and acute lymphoblastic leukaemia in childhood: historical cohort study
In a historical cohort study of all singleton live births in Northern Ireland from 1971–86 (n=434 933) associations between early life factors and childhood acute lymphoblastic leukaemia were investigated. Multivariable analyses showed a positive association between high paternal age (⩾35 years) and acute lymphoblastic leukaemia (relative risk=1.49; 95% confidence interval (CI)=0.96–2.31) but no association with maternal age. High birth weight (⩾3500 g) was positively associated with acute lymphoblastic leukaemia (relative risk=1.66; 95% CI=1.18–2.33). Children of mothers with a previous miscarriage or increased gestation (⩾40 weeks) had reduced risks of ALL (respective relative risks=0.49; 95% CI=0.29–0.80, and 0.67; 95% CI=0.48–0.94). Children born into more crowded households (⩾1 person per room) had substantially lower risks than children born into less crowded homes with also some evidence of a lower risk for children born into homes with three adults (relative risks=0.56; 95% CI=0.35–0.91 and 0.58; 95% CI=0.21–1.61 respectively). These findings indicate that several early life factors, including living conditions in childhood and maternal miscarriage history, influence risk of acute lymphoblastic leukaemia in childhood
The Eyes Have It: Sex and Sexual Orientation Differences in Pupil Dilation Patterns
Recent research suggests profound sex and sexual orientation differences in sexual response. These results, however, are based on measures of genital arousal, which have potential limitations such as volunteer bias and differential measures for the sexes. The present study introduces a measure less affected by these limitations. We assessed the pupil dilation of 325 men and women of various sexual orientations to male and female erotic stimuli. Results supported hypotheses. In general, self-reported sexual orientation corresponded with pupil dilation to men and women. Among men, substantial dilation to both sexes was most common in bisexual-identified men. In contrast, among women, substantial dilation to both sexes was most common in heterosexual-identified women. Possible reasons for these differences are discussed. Because the measure of pupil dilation is less invasive than previous measures of sexual response, it allows for studying diverse age and cultural populations, usually not included in sexuality research
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