Single photon absorption by a single quantum emitter

We show that a three-level lambda quantum emitter with equal spontaneous emission rates on both optically active transitions can absorb an incident light field with a probability approaching unity, provided that the focused light profile matches that of the emitter dipole emission pattern. Even with realistic focusing geometries, our results could find applications in long-distance entanglement of spin qubits.Comment: 4 pages, 4 figure

Original Sins of Insurance systems: The case of the Greek Occupational Risk Insurance Scheme, IKA-ETAM

This paper aims to estimate the cost of pensions, compensations and foregone contributions due to occupational accidents for the main Greek social security institution IKA-ETAM. Through this process, conclusions transferable to other occupational risk insurance systems are drawn. Both prevalence and incidence approach are applied on analytical data for active and new occupational accident pensions and compensations of IKA-ETAM for 2007. Cost is estimated as the difference of all costs and benefits with and without the accident. Prevalence approach leads to an estimate of €148,539,548.40 against an estimate of €77,707,206.98 with incidence approach. In both approaches, cost of temporary disability is estimated at €18,464,021.61 and foregone contributions (opportunity cost) account for 27% of total cost. Although wages raised, contribution and compensation rates remained stable and accidents decreased for IKA-ETAM contribution payers during last decades, the viability of the system is threatened. The reasons identified are a) the increase of the average time off-work per accident and b) the backload, due to the large number of accidents and pensions in the past

Blind assessment of localisation microscope image resolution

Abstract Background This paper analyses the resolution achieved in localisation microscopy experiments. The resolution is an essential metric for the correct interpretation of super-resolution images, but it varies between specimens due to different localisation precisions and densities. Methods By analysing localisation microscopy as a statistical method of Density Estimation, we present a method that produces a blind estimate of the resolution in a super-resolved image. This estimate is derived directly from the raw image data without the need for comparisons with known calibration specimens. It is corroborated with simulated and experimental data. Results and discussion Localisation microscopy has a resolution limit equal to 2σ, where σ is the r.m.s. localisation precision, evaluated as an average Thompson precision, Cramer Rao bound, or otherwise. Further, for a limited-sampling case in which there is only one localisation per fluorophore, the expected resolution of an optimised super-resolution image is worsened to approximately 3σ, due to smoothing processes that are necessarily involved in visualising the specimen with limited data. This 2σ or 3σ resolution can be estimated for any localisation microscopy specimen, and this metric can corroborate or replace empirical estimates of resolution. Other quantifiable resolution losses arise from sparse labelling, fluorescent label size, and motion blur.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

A label-free, quantitative assay of amyloid fibril growth based on intrinsic fluorescence.

Kinetic assay of seeded growth: The graph shows the variation in intrinsic fluorescence intensity of amyloid fibrils. Fluorescence increases during the seeded aggregation of α-synuclein seeds with α-synuclein monomeric protein (blue curve) but not when α-synuclein seeds are incubated with β-synuclein monomeric protein (black curve), thus showing that no seeded growth occurred in this case

Advanced imaging of tau pathology in Alzheimer Disease: New perspectives from super resolution microscopy and label-free nanoscopy.

Alzheimer's disease (AD) is the main cause of dementia in the elderly population. Over 30 million people worldwide are living with dementia and AD prevalence is projected to increase dramatically in the next two decades. In terms of neuropathology, AD is characterized by two major cerebral hallmarks: extracellular β-amyloid (Aβ) plaques and intracellular Tau inclusions, which start accumulating in the brain 15-20 years before the onset of symptoms. Within this context, the scientific community worldwide is undertaking a wide research effort to detect AD pathology at its earliest, before symptoms appear. Neuroimaging of Aβ by positron emission tomography (PET) is clinically available and is a promising modality for early detection of Aβ pathology and AD diagnosis. Substantive efforts are ongoing to develop advanced imaging techniques for early detection of Tau pathology. Here, we will briefly describe the key features of Tau pathology and its heterogeneity across various neurodegenerative diseases bearing cerebral Tau inclusions (i.e., tauopathies). We will outline the current status of research on Tau-specific PET tracers and their clinical development. Finally, we will discuss the potential application of novel super-resolution and label-free techniques for investigating Tau pathology at the experimental level and their potential application for AD diagnosis. Microsc. Res. Tech. 79:677-683, 2016. © 2016 Wiley Periodicals, Inc.LG acknowledges funding from the European Community's Seventh Framework Program (FP7/2012-2015) under grant agreement n°280804. GSSK acknowledges funding from the U.K. Medical Research Council (MR/K015850/1 and MR/K02292X/1), Alzheimer's Research UK (ARUK-EG2012A-1), U.K. Engineering and Physical Sciences Research Council (EPSRC) (EP/H018301/1) and the Wellcome Trust (089703/Z/09/Z).This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/jemt.2269

Electrical control of nonlinear quantum optics in a nano-photonic waveguide

Quantum photonics is a rapidly developing platform for future quantum network applications. Waveguide-based architectures, in which embedded quantum emitters act as both nonlinear elements to mediate photon–photon interactions and as highly coherent single-photon sources, offer a highly promising route to realize such networks. A key requirement for the scale-up of the waveguide architecture is local control and tunability of individual quantum emitters. Here, we demonstrate electrical control, tuning, and switching of the nonlinear photon–photon interaction arising due to a quantum dot embedded in a single-mode nano-photonic waveguide. A power-dependent waveguide transmission extinction as large as 40±2% is observed on resonance. Photon statistics measurements show clear, voltage-controlled bunching of the transmitted light and antibunching of the reflected light, demonstrating the single-photon, quantum character of the nonlinearity. Importantly, the same architecture is also shown to act as a source of highly coherent, electrically tunable single photons. Overall, the platform presented addresses the essential requirements for the implementation of photonic gates for scalable nano-photonic-based quantum information processing

Proton Transfer and Structure-Specific Fluorescence in Hydrogen Bond-Rich Protein Structures.

Protein structures which form fibrils have recently been shown to absorb light at energies in the near UV range and to exhibit a structure-specific fluorescence in the visible range even in the absence of aromatic amino acids. However, the molecular origin of this phenomenon has so far remained elusive. Here, we combine ab initio molecular dynamics simulations and fluorescence spectroscopy to demonstrate that these intrinsically fluorescent protein fibrils are permissive to proton transfer across hydrogen bonds which can lower electron excitation energies and thereby decrease the likelihood of energy dissipation associated with conventional hydrogen bonds. The importance of proton transfer on the intrinsic fluorescence observed in protein fibrils is signified by large reductions in the fluorescence intensity upon either fully protonating, or deprotonating, the fibrils at pH = 0 or 14, respectively. Thus, our results point to the existence of a structure-specific fluorophore that does not require the presence of aromatic residues or multiple bond conjugation that characterize conventional fluorescent systems. The phenomenon may have a wide range of implications in biological systems and in the design of self-assembled functional materials.We thank Prof. M. Sauer for useful discussions. This work was funded by grants from the Medical Research Council UK (MR/K015850/1 and MR/K02292X/1), Alzheimer Research UK (ARUKEG2012A-1), U.K. EPSRC (EP/H018301/1) and the Wellcome Trust (089703/Z/09/Z). D.P. wishes to acknowledge support from the Swiss National Science Foundation and the Wellcome Trust through personal fellowships. We thank LMB Visual Aids for graphics support.This is the author accepted manuscript. The final version is available from the American Chemical Society via http://dx.doi.org/10.1021/jacs.5b1101

Direct observation of heterogeneous amyloid fibril growth kinetics via two-color super-resolution microscopy.

The self-assembly of normally soluble proteins into fibrillar amyloid structures is associated with a range of neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases. In the present study, we show that specific events in the kinetics of the complex, multistep aggregation process of one such protein, α-synuclein, whose aggregation is a characteristic hallmark of Parkinson's disease, can be followed at the molecular level using optical super-resolution microscopy. We have explored in particular the elongation of preformed α-synuclein fibrils; using two-color single-molecule localization microscopy we are able to provide conclusive evidence that the elongation proceeds from both ends of the fibril seeds. Furthermore, the technique reveals a large heterogeneity in the growth rates of individual fibrils; some fibrils exhibit no detectable growth, whereas others extend to more than ten times their original length within hours. These large variations in the growth kinetics can be attributed to fibril structural polymorphism. Our technique offers new capabilities in the study of amyloid growth dynamics at the molecular level and is readily translated to the study of the self-assembly of other nanostructures

A computational study on how structure influences the optical properties in model crystal structures of amyloid fibrils

Amyloid fibrils have been shown to have peculiar optical properties since they can exhibit fluorescence in the absence of aromatic residues. In a recent study, we have shown that proton transfer (PT) events along hydrogen bonds (HBs) are coupled to absorption in the near UV range. Here, we gain more insights into the different types of hydrogen bonding interactions that occur in our model systems and the molecular factors that control the susceptibility of the protons to undergo PT and how this couples to the optical properties. In the case of the strong N–C termini interactions, a nearby methionine residue stabilizes the non-zwitterionic NH$_{2}$–COOH pair, while zwitterionic NH$_{3}$+–COO– is stabilized by the proximity of nearby crystallographic water molecules. Proton motion along the hydrogen bonds in the fibril is intimately coupled to the compression of the heavier atoms, similar to what is observed in bulk water. Small changes in the compression of the hydrogen bonds in the protein can lead to significant changes in both the ground and excited state potential energy surfaces associated with PT. Finally, we also reinforce the importance of nuclear quantum fluctuations of protons in the HBs of the amyloid proteins

Nanoscopic insights into seeding mechanisms and toxicity of α-synuclein species in neurons.

New strategies for visualizing self-assembly processes at the nanoscale give deep insights into the molecular origins of disease. An example is the self-assembly of misfolded proteins into amyloid fibrils, which is related to a range of neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases. Here, we probe the links between the mechanism of α-synuclein (AS) aggregation and its associated toxicity by using optical nanoscopy directly in a neuronal cell culture model of Parkinson's disease. Using superresolution microscopy, we show that protein fibrils are taken up by neuronal cells and act as prion-like seeds for elongation reactions that both consume endogenous AS and suppress its de novo aggregation. When AS is internalized in its monomeric form, however, it nucleates and triggers the aggregation of endogenous AS, leading to apoptosis, although there are no detectable cross-reactions between externally added and endogenous protein species. Monomer-induced apoptosis can be reduced by pretreatment with seed fibrils, suggesting that partial consumption of the externally added or excess soluble AS can be significantly neuroprotective.We thank Dr Q. Jeng and Dr A. Stephens for technical assistance and Dr J. Skepper for TEM imaging. This work was funded by grants from the U.K. Medical Research Council (MR/K015850/1 and MR/K02292X/1), Alzheimer’s Research UK (ARUK-EG2012A-1), U.K. Engineering and Physical Sciences Research Council (EPSRC) (EP/H018301/1) and the Wellcome Trust (089703/Z/09/Z). D.P. wishes to acknowledge support from the Swiss National Science Foundation and the Wellcome Trust through personal fellowships. A.K.B thanks Magdalene College, Cambridge and the Leverhulme Trust for support.This is the author accepted manuscript. The final version is available from the National Academy of Sciences via http://dx.doi.org/10.1073/pnas.1516546113