Pathogenicity of anti-ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura.

BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease in which anti-ADAMTS13 autoantibodies cause severe enzyme deficiency. ADAMTS13 deficiency causes the loss of regulation of von Willebrand factor multimeric size and platelet-tethering function, which results in the formation of disseminated microvascular platelet microthrombi. Precisely how anti-ADAMTS13 autoantibodies, or antibody subsets, cause ADAMTS13 deficiency (ADAMTS13 activity generally < 10%) has not been formally investigated. METHODS: We analysed 92 acquired TTP episodes at presentation, through treatment and remission/relapse using epitope mapping and functional analyses to understand the pathogenic mechanisms of anti-ADAMTS13 IgG. RESULTS: 89/92 of TTP episodes had IgG recognising the ADAMTS13 N-terminal domains. The central spacer domain was the only N-terminal antigenic target detected. 38/92 TTP episodes had autoantibodies recognising the N-terminal domains alone; 54/92 TTP episodes also had antibodies against the ADAMTS13 C-terminal domains (TSP2-8 and/or CUB domains). Changes in autoantibody specificity were detected in 9/16 patients at relapse, suggesting a continued development of the disease. Functional analyses on IgG from 43 patients revealed inhibitory IgG were limited to anti-spacer domain antibodies. However, 15/43 patients had autoantibodies with no detectable inhibitory action and as many as 32/43 patients had autoantibodies with inhibitory function that was insufficient to account for the severe deficiency state, suggesting that in many patients there is an alternative pathogenic mechanism. We therefore analysed plasma ADAMTS13 antigen levels in 91 acquired TTP presentation samples. We demonstrated markedly reduced ADAMTS13 antigen levels in all presentation samples, median 6% normal (range 0-47%), with 84/91 patients having < 25% ADAMTS13 antigen. ADAMTS13 antigen in the lowest quartile at first presentation was associated with increased mortality (odds ratio 5.7). CONCLUSIONS: Anti-spacer domain autoantibodies are the major inhibitory antibodies in acquired TTP. However, depletion of ADAMTS13 antigen (rather than enzyme inhibition) is a dominant pathogenic mechanism. ADAMTS13 antigen levels at presentation have prognostic significance. Taken together, our results provide new insights into the pathophysiology of acquired TTP

Current-oscillator correlation and Fano factor spectrum of quantum shuttle with finite bias voltage and temperature

A general master equation is derived to describe an electromechanical single-dot transistor in the Coulomb blockade regime. In the equation, Fermi distribution functions in the two leads are taken into account, which allows one to study the system as a function of bias voltage and temperature of the leads. Furthermore, we treat the coherent interaction mechanism between electron tunneling events and the dynamics of excited vibrational modes. Stationary solutions of the equation are numerically calculated. We show current through the oscillating island at low temperature appears step like characteristics as a function of the bias voltage and the steps depend on mean phonon number of the oscillator. At higher temperatures the current steps would disappear and this event is accompanied by the emergence of thermal noise of the charge transfer. When the system is mainly in the ground state, zero frequency Fano factor of current manifests sub-Poissonian noise and when the system is partially driven into its excited states it exhibits super-Poissonian noise. The difference in the current noise would almost be removed for the situation in which the dissipation rate of the oscillator is much larger than the bare tunneling rates of electrons.Comment: 14 pages, 8 figure

Entanglement and teleportation via chaotic system

The dynamics of entangled state interacting with a single cavity mode is investigated in the presence of a random parameter. We have shown that degree of entanglement decays with time and rate of decay is defined by features of random parameter. Quantum teleportation through dissipative channal and teleportation fidelity as a function of damping rates has been studied. The sensitivity of the fidelity with respect to random parameter is discussed. We have evaluated the time interval during which one can perform the quantum teleportation and send the information with reasonable fidelity, for a given values of correlation length of random parameter.Comment: Accepted in Physica

Probing the nanoscale phase separation in binary photovoltaic blends of poly(3-hexylthiophene) and methanofullerene by energy transfer

The generation of charge carriers in organic photovoltaic devices requires exciton diffusion to an interface of electron donor and acceptor materials, where charge separation occurs. We report a time resolved study of fluorescence quenching in films of poly(3-hexylthiophene) containing a range of fractions of the electron acceptor [6,6]-phenyl-C61-butyric acid methyl ester (PCBM). We show that energy transfer from P3HT to PCBM helps to bring excitons to the interface, where they dissociate into charge carriers. Fluorescence quenching in blends with ≤50 wt% of PCBM is controlled by exciton diffusion in P3HT. This allows us to estimate the average size of PCBM domains to be about 9 nm in the 1:1 blend. The implications for polymer solar cells are discussed

Integral Relaxation Time of Single-Domain Ferromagnetic Particles

The integral relaxation time \tau_{int} of thermoactivating noninteracting single-domain ferromagnetic particles is calculated analytically in the geometry with a magnetic field H applied parallel to the easy axis. It is shown that the drastic deviation of \tau_{int}^{-1} from the lowest eigenvalue of the Fokker-Planck equation \Lambda_1 at low temperatures, starting from some critical value of H, is the consequence of the depletion of the upper potential well. In these conditions the integral relaxation time consists of two competing contributions corresponding to the overbarrier and intrawell relaxation processes.Comment: 8 pages, 3 figure

Absorbing state phase transition with competing quantum and classical fluctuations

Stochastic processes with absorbing states feature examples of non-equilibrium universal phenomena. While the classical regime has been thoroughly investigated in the past, relatively little is known about the behavior of these non-equilibrium systems in the presence of quantum fluctuations. Here we theoretically address such a scenario in an open quantum spin model which in its classical limit undergoes a directed percolation phase transition. By mapping the problem to a non-equilibrium field theory, we show that the introduction of quantum fluctuations stemming from coherent, rather than statistical, spin-flips alters the nature of the transition such that it becomes first-order. In the intermediate regime, where classical and quantum dynamics compete on equal terms, we highlight the presence of a bicritical point with universal features different from the directed percolation class in low dimension. We finally propose how this physics could be explored within gases of interacting atoms excited to Rydberg states

Testing foundations of quantum mechanics with photons

The foundational ideas of quantum mechanics continue to give rise to counterintuitive theories and physical effects that are in conflict with a classical description of Nature. Experiments with light at the single photon level have historically been at the forefront of tests of fundamental quantum theory and new developments in photonics engineering continue to enable new experiments. Here we review recent photonic experiments to test two foundational themes in quantum mechanics: wave-particle duality, central to recent complementarity and delayed-choice experiments; and Bell nonlocality where recent theoretical and technological advances have allowed all controversial loopholes to be separately addressed in different photonics experiments.Comment: 10 pages, 5 figures, published as a Nature Physics Insight review articl

Multi-threshold second-order phase transition

We present a theory of the multi-threshold second-order phase transition, and experimentally demonstrate the multi-threshold second-order phase transition phenomenon. With carefully selected parameters, in an external cavity diode laser system, we observe second-order phase transition with multiple (three or four) thresholds in the measured power-current-temperature three dimensional phase diagram. Such controlled death and revival of second-order phase transition sheds new insight into the nature of ubiquitous second-order phase transition. Our theory and experiment show that the single threshold second-order phase transition is only a special case of the more general multi-threshold second-order phase transition, which is an even richer phenomenon.Comment: 5 pages, 3 figure

Testimonial Injustice and Vulnerability: A Qualitative Analysis of Participation in the Court of Protection

This article explores participation in Court of Protection (COP) proceedings by people considered vulnerable. The paper is based on original data obtained from observing COP proceedings and reviewing COP case files. It is argued that the observed absence of the subject of proceedings is a form of testimonial injustice, that is, a failure to value a person in their capacity as a giver of knowledge. The issue of competence to give evidence is considered but it is argued that it is not the formal evidential rules that prohibit a vulnerable adult from giving evidence. Instead, it is the result of a persistent assumption that they are inherently vulnerable and therefore lack credibility as a knowledge giver. This assumption results in the voices of vulnerable adults being routinely absent from legal proceedings. It is argued that having a voice in the courtroom is essential and has a number of intrinsic and instrumental benefits. The paper concludes with a discussion about the implications of the research, including the current trend towards the increased use of special measures, and recommends a presumption in favour of the subject of COP proceedings giving evidence

Nonequilibrium effective field theory for absorbing state phase transitions in driven open quantum spin systems

Phase transitions to absorbing states are among the simplest examples of critical phenomena out of equilibrium. The characteristic feature of these models is the presence of a fluctuationless configuration which the dynamics cannot leave, which has proved a rather stringent requirement in experiments. Recently, a proposal to seek such transitions in highly tuneable systems of cold atomic gases offers to probe this physics and, at the same time, to investigate the robustness of these transitions to quantum coherent effects. Here we specifically focus on the interplay between classical and quantum fluctuations in a simple driven open quantum model which, in the classical limit, reproduces a contact process, which is known to undergo a continuous transition in the "directed percolation" universality class. We derive an effective long-wavelength field theory for the present class of open spin systems and show that, due to quantum fluctuations, the nature of the transition changes from second to first order, passing through a bicritical point which appears to belong instead to the "tricritical directed percolation" class