436 research outputs found
Maximal entanglement versus entropy for mixed quantum states
Get PDFMaximally entangled mixed states are those states that, for a given mixedness, achieve the greatest possible entanglement. For two-qubit systems and for various combinations of entanglement and mixedness measures, the form of the corresponding maximally entangled mixed states is determined primarily analytically. As measures of entanglement, we consider entanglement of formation, relative entropy of entanglement, and negativity; as measures of mixedness, we consider linear and von Neumann entropies. We show that the forms of the maximally entangled mixed states can vary with the combination of (entanglement and mixedness) measures chosen. Moreover, for certain combinations, the forms of the maximally entangled mixed states can change discontinuously at a specific value of the entropy. Along the way, we determine the states that, for a given value of entropy, achieve maximal violation of Bell's inequality
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Scaling laws and dynamics of bubble coalescence
Get PDFThe coalescence of bubbles and drops plays a central role in nature and industry. During coalescence, two bubbles or drops touch and merge into one as the neck connecting them grows from microscopic to macroscopic scales. The hydrodynamic singularity that arises when two bubbles or drops have just touched and the flows that ensue have been studied thoroughly when two drops coalesce in a dynamically passive outer fluid. In this paper, the coalescence of two identical and initially spherical bubbles, which are idealized as voids, that are surrounded by an incompressible Newtonian liquid is analyzed by numerical simulation. This problem has recently been studied (a) experimentally using high-speed imaging and (b) by asymptotic analysis in which the dynamics is analyzed by determining the growth of a hole in the thin liquid sheet separating the two bubbles. In the latter, advantage is taken of the fact that the flow in the thin sheet of non-constant thickness is governed by a set of one-dimensional, radial extensional flow equations. While these studies agree on the power law scaling of the variation of the minimum neck radius with time, they disagree with respect to the numerical value of the prefactors in the scaling laws. In order to reconcile these differences and also provide insights into the dynamics that are difficult to probe by either of the aforementioned approaches, simulations are used to access both earlier times than it has been possible in the experiments and also later times when asymptotic analysis is no longer applicable. Early times and extremely small length scales are attained in the new simulations through the use of a truncated domain approach. Furthermore, it is shown by direct numerical simulations in which the flow within the bubbles is also determined along with the flow exterior to them that idealizing the bubbles as passive voids has virtually no effect on the scaling laws relating minimum neck radius and time.This research was sponsored by the Petroleum Research Fund of the American Chemical Society, the Basic Energy Sciences Program of the United States Department of Energy, and the Engineering and Physical Sciences Research Council
WASp-dependent actin cytoskeleton stability at the dendritic cell immunological synapse is required for extensive, functional T cell contacts
Get PDFThe immunological synapse is a highly structured and molecularly dynamic interface between communicating immune cells. Although the immunological synapse promotes T cell activation by dendritic cells, the specific organization of the immunological synapse on the dendritic cell side in response to T cell engagement is largely unknown. In this study, confocal and electron microscopy techniques were used to investigate the role of dendritic cell actin regulation in immunological synapse formation, stabilization, and function. In the dendritic cell-restricted absence of the Wiskott-Aldrich syndrome protein, an important regulator of the actin cytoskeleton in hematopoietic cells, the immunological synapse contact with T cells occupied a significantly reduced surface area. At a molecular level, the actin network localized to the immunological synapse exhibited reduced stability, in particular, of the actin-related protein-2/3-dependent, short-filament network. This was associated with decreased polarization of dendritic cell-associated ICAM-1 and MHC class II, which was partially dependent on Wiskott-Aldrich syndrome protein phosphorylation. With the use of supported planar lipid bilayers incorporating anti-ICAM-1 and anti-MHC class II antibodies, the dendritic cell actin cytoskeleton organized into recognizable synaptic structures but interestingly, formed Wiskott-Aldrich syndrome protein-dependent podosomes within this area. These findings demonstrate that intrinsic dendritic cell cytoskeletal remodeling is a key regulatory component of normal immunological synapse formation, likely through consolidation of adhesive interaction and modulation of immunological synapse stability
The effect of distance on reaction time in aiming movements
Get PDFTarget distance affects movement duration in aiming tasks but its effect on reaction time (RT) is poorly documented. RT is a function of both preparation and initiation. Experiment 1 pre-cued movement (allowing advanced preparation) and found no influence of distance on RT. Thus, target distance does not affect initiation time. Experiment 2 removed pre-cue information and found that preparing a movement of increased distance lengthens RT. Experiment 3 explored movements to targets of cued size at non-cued distances and found size altered peak speed and movement duration but RT was influenced by distance alone. Thus, amplitude influences preparation time (for reasons other than altered duration) but not initiation time. We hypothesise that the RT distance effect might be due to the increased number of possible trajectories associated with further targets: a hypothesis that can be tested in future experiments
Regulation of cell protrusions by small GTPases during fusion of the neural folds.
Get PDFEpithelial fusion is a crucial process in embryonic development, and its failure underlies several clinically important birth defects. For example, failure of neural fold fusion during neurulation leads to open neural tube defects including spina bifida. Using mouse embryos, we show that cell protrusions emanating from the apposed neural fold tips, at the interface between the neuroepithelium and the surface ectoderm, are required for completion of neural tube closure. By genetically ablating the cytoskeletal regulators Rac1 or Cdc42 in the dorsal neuroepithelium, or in the surface ectoderm, we show that these protrusions originate from surface ectodermal cells and that Rac1 is necessary for the formation of membrane ruffles which typify late closure stages, whereas Cdc42 is required for the predominance of filopodia in early neurulation. This study provides evidence for the essential role and molecular regulation of membrane protrusions prior to fusion of a key organ primordium in mammalian development
REEP6 Deficiency Leads to Retinal Degeneration through Disruption of ER Homeostasis and Protein Trafficking
Get PDFRetinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy. We recently identified mutations in REEP6, which encodes the receptor expression enhancing protein 6, in several families with autosomal recessive RP. REEP6 is related to the REEP and Yop1p family of ER shaping proteins and potential receptor accessory proteins, but the role of REEP6 in the retina is unknown. Here we characterise the disease mechanisms associated with loss of REEP6 function using a Reep6 knockout mouse generated by CRISPR/Cas9 gene editing. In control mice REEP6 was localised to the inner segment and outer plexiform layer of rod photoreceptors. The Reep6-/- mice exhibited progressive photoreceptor degeneration from P20 onwards. Ultrastructural analyses at P20 by transmission electron microscopy and 3View serial block face scanning EM revealed an expansion of the distal ER in the Reep6-/- rods and an increase in their number of mitochondria. Electroretinograms revealed photoreceptor dysfunction preceded degeneration, suggesting potential defects in phototransduction. There was no effect on the traffic of rhodopsin, Rom1 or peripherin/rds; however, the retinal guanylate cyclases GC1 and GC2 were severely affected in the Reep6 knockout animals, with almost undetectable expression. These changes correlated with an increase in C/EBP homologous protein (CHOP) expression and the activation of caspase 12, suggesting that ER stress contributes to cell death. Collectively, these data suggest that REEP6 plays an essential role in maintaining cGMP homeostasis though facilitating the stability and/or trafficking of guanylate cyclases and maintaining ER and mitochondrial homeostasis
Identification and Correction of Mechanisms Underlying Inherited Blindness in Human iPSC-Derived Optic Cups
Get PDFLeber congenital amaurosis (LCA) is an inherited retinal dystrophy that causes childhood blindness. Photoreceptors are especially sensitive to an intronic mutation in the cilia-related gene CEP290, which causes missplicing and premature termination, but the basis of this sensitivity is unclear. Here, we generated differentiated photoreceptors in three-dimensional optic cups and retinal pigment epithelium (RPE) from iPSCs with this common CEP290 mutation to investigate disease mechanisms and evaluate candidate therapies. iPSCs differentiated normally into RPE and optic cups, despite abnormal CEP290 splicing and cilia defects. The highest levels of aberrant splicing and cilia defects were observed in optic cups, explaining the retinal-specific manifestation of this CEP290 mutation. Treating optic cups with an antisense morpholino effectively blocked aberrant splicing and restored expression of full-length CEP290, restoring normal cilia-based protein trafficking. These results provide a mechanistic understanding of the retina-specific phenotypes in CEP290 LCA patients and potential strategies for therapeutic intervention
Rescue of mutant rhodopsin traffic by metformin-induced AMPK activation accelerates photoreceptor degeneration
Get PDFProtein misfolding caused by inherited mutations leads to loss of protein function and potentially toxic 'gain of function', such as the dominant P23H rhodopsin mutation that causes retinitis pigmentosa (RP). Here, we tested whether the AMPK activator metformin could affect the P23H rhodopsin synthesis and folding. In cell models, metformin treatment improved P23H rhodopsin folding and traffic. In animal models of P23H RP, metformin treatment successfully enhanced P23H traffic to the rod outer segment, but this led to reduced photoreceptor function and increased photoreceptor cell death. The metformin-rescued P23H rhodopsin was still intrinsically unstable and led to increased structural instability of the rod outer segments. These data suggest that improving the traffic of misfolding rhodopsin mutants is unlikely to be a practical therapy, because of their intrinsic instability and long half-life in the outer segment, but also highlights the potential of altering translation through AMPK to improve protein function in other protein misfolding diseases
Rapid global fitting of large fluorescence lifetime imaging microscopy datasets
Get PDFFluorescence lifetime imaging (FLIM) is widely applied to obtain quantitative information from fluorescence signals, particularly using Förster Resonant Energy Transfer (FRET) measurements to map, for example, protein-protein interactions. Extracting FRET efficiencies or population fractions typically entails fitting data to complex fluorescence decay models but such experiments are frequently photon constrained, particularly for live cell or in vivo imaging, and this leads to unacceptable errors when analysing data on a pixel-wise basis. Lifetimes and population fractions may, however, be more robustly extracted using global analysis to simultaneously fit the fluorescence decay data of all pixels in an image or dataset to a multi-exponential model under the assumption that the lifetime components are invariant across the image (dataset). This approach is often considered to be prohibitively slow and/or computationally expensive but we present here a computationally efficient global analysis algorithm for the analysis of time-correlated single photon counting (TCSPC) or time-gated FLIM data based on variable projection. It makes efficient use of both computer processor and memory resources, requiring less than a minute to analyse time series and multiwell plate datasets with hundreds of FLIM images on standard personal computers. This lifetime analysis takes account of repetitive excitation, including fluorescence photons excited by earlier pulses contributing to the fit, and is able to accommodate time-varying backgrounds and instrument response functions. We demonstrate that this global approach allows us to readily fit time-resolved fluorescence data to complex models including a four-exponential model of a FRET system, for which the FRET efficiencies of the two species of a bi-exponential donor are linked, and polarisation-resolved lifetime data, where a fluorescence intensity and bi-exponential anisotropy decay model is applied to the analysis of live cell homo-FRET data. A software package implementing this algorithm, FLIMfit, is available under an open source licence through the Open Microscopy Environment
Efficient quantum computing using coherent photon conversion
Full text linkSingle photons provide excellent quantum information carriers, but current
schemes for preparing, processing and measuring them are inefficient. For
example, down-conversion provides heralded, but randomly timed single photons,
while linear-optics gates are inherently probabilistic. Here, we introduce a
deterministic scheme for photonic quantum information. Our single, versatile
process---coherent photon conversion---provides a full suite of photonic
quantum processing tools, from creating high-quality heralded single- and
multiphoton states free of higher-order imperfections to implementing
deterministic multiqubit entanglement gates and high-efficiency detection. It
fulfils all requirements for a scalable photonic quantum computing
architecture. Using photonic crystal fibres, we experimentally demonstrate a
four-colour nonlinear process usable for coherent photon conversion and show
that current technology provides a feasible path towards deterministic
operation. Our scheme, based on interacting bosonic fields, is not restricted
to optical systems, but could also be implemented in optomechanical,
electromechanical and superconducting systems which exhibit extremely strong
intrinsic nonlinearities.Comment: 12 pages, 9 figure
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