Induced pluripotent stem cell-based disease modeling identifies ligand-induced decay of megalin as a cause of Donnai-Barrow syndrome

Donnai-Barrow syndrome (DBS) is an autosomal-recessive disorder characterized by multiple pathologies including malformation of forebrain and eyes, as well as resorption defects of the kidney proximal tubule. The underlying cause of DBS are mutations in LRP2, encoding the multifunctional endocytic receptor megalin. Here, we identified a unique missense mutation R3192Q of LRP2 in an affected family that may provide novel insights into the molecular causes of receptor dysfunction in the kidney proximal tubule and other tissues affected in DBS. Using patient-derived induced pluripotent stem cell lines we generated neuroepithelial and kidney cell types as models of the disease. Using these cell models, we documented the inability of megalinR3192Q to properly discharge ligand and ligand-induced receptor decay in lysosomes. Thus, mutant receptors are aberrantly targeted to lysosomes for catabolism, essentially depleting megalin in the presence of ligand in this affected family

Meixner class of non-commutative generalized stochastic processes with freely independent values I. A characterization

Let $T$ be an underlying space with a non-atomic measure $\sigma$ on it (e.g. $T=\mathbb R^d$ and $\sigma$ is the Lebesgue measure). We introduce and study a class of non-commutative generalized stochastic processes, indexed by points of $T$, with freely independent values. Such a process (field), $\omega=\omega(t)$, $t\in T$, is given a rigorous meaning through smearing out with test functions on $T$, with $\int_T \sigma(dt)f(t)\omega(t)$ being a (bounded) linear operator in a full Fock space. We define a set $\mathbf{CP}$ of all continuous polynomials of $\omega$, and then define a con-commutative $L^2$-space $L^2(\tau)$ by taking the closure of $\mathbf{CP}$ in the norm $\|P\|_{L^2(\tau)}:=\|P\Omega\|$, where $\Omega$ is the vacuum in the Fock space. Through procedure of orthogonalization of polynomials, we construct a unitary isomorphism between $L^2(\tau)$ and a (Fock-space-type) Hilbert space $\mathbb F=\mathbb R\oplus\bigoplus_{n=1}^\infty L^2(T^n,\gamma_n)$, with explicitly given measures $\gamma_n$. We identify the Meixner class as those processes for which the procedure of orthogonalization leaves the set $\mathbf {CP}$ invariant. (Note that, in the general case, the projection of a continuous monomial of oder $n$ onto the $n$-th chaos need not remain a continuous polynomial.) Each element of the Meixner class is characterized by two continuous functions $\lambda$ and $\eta\ge0$ on $T$, such that, in the $\mathbb F$ space, $\omega$ has representation \omega(t)=\di_t^\dag+\lambda(t)\di_t^\dag\di_t+\di_t+\eta(t)\di_t^\dag\di^2_t, where \di_t^\dag and \di_t are the usual creation and annihilation operators at point $t$

Classification of multipartite entangled states by multidimensional determinants

We find that multidimensional determinants "hyperdeterminants", related to entanglement measures (the so-called concurrence or 3-tangle for the 2 or 3 qubits, respectively), are derived from a duality between entangled states and separable states. By means of the hyperdeterminant and its singularities, the single copy of multipartite pure entangled states is classified into an onion structure of every closed subset, similar to that by the local rank in the bipartite case. This reveals how inequivalent multipartite entangled classes are partially ordered under local actions. In particular, the generic entangled class of the maximal dimension, distinguished as the nonzero hyperdeterminant, does not include the maximally entangled states in Bell's inequalities in general (e.g., in the $n \geq 4$ qubits), contrary to the widely known bipartite or 3-qubit cases. It suggests that not only are they never locally interconvertible with the majority of multipartite entangled states, but they would have no grounds for the canonical n-partite entangled states. Our classification is also useful for the mixed states.Comment: revtex4, 10 pages, 4 eps figures with psfrag; v2 title changed, 1 appendix added, to appear in Phys. Rev.

Dynamics of Collective Decoherence and Thermalization

We analyze the dynamics of N interacting spins (quantum register) collectively coupled to a thermal environment. Each spin experiences the same environment interaction, consisting of an energy conserving and an energy exchange part. We find the decay rates of the reduced density matrix elements in the energy basis. We show that if the spins do not interact among each other, then the fastest decay rates of off-diagonal matrix elements induced by the energy conserving interaction is of order N^2, while that one induced by the energy exchange interaction is of the order N only. Moreover, the diagonal matrix elements approach their limiting values at a rate independent of N. For a general spin system the decay rates depend in a rather complicated (but explicit) way on the size N and the interaction between the spins. Our method is based on a dynamical quantum resonance theory valid for small, fixed values of the couplings. We do not make Markov-, Born- or weak coupling (van Hove) approximations

Statistical distribution of quantum entanglement for a random bipartite state

We compute analytically the statistics of the Renyi and von Neumann entropies (standard measures of entanglement), for a random pure state in a large bipartite quantum system. The full probability distribution is computed by first mapping the problem to a random matrix model and then using a Coulomb gas method. We identify three different regimes in the entropy distribution, which correspond to two phase transitions in the associated Coulomb gas. The two critical points correspond to sudden changes in the shape of the Coulomb charge density: the appearance of an integrable singularity at the origin for the first critical point, and the detachement of the rightmost charge (largest eigenvalue) from the sea of the other charges at the second critical point. Analytical results are verified by Monte Carlo numerical simulations. A short account of some of these results appeared recently in Phys. Rev. Lett. {\bf 104}, 110501 (2010).Comment: 7 figure

How brains make decisions

This chapter, dedicated to the memory of Mino Freund, summarizes the Quantum Decision Theory (QDT) that we have developed in a series of publications since 2008. We formulate a general mathematical scheme of how decisions are taken, using the point of view of psychological and cognitive sciences, without touching physiological aspects. The basic principles of how intelligence acts are discussed. The human brain processes involved in decisions are argued to be principally different from straightforward computer operations. The difference lies in the conscious-subconscious duality of the decision making process and the role of emotions that compete with utility optimization. The most general approach for characterizing the process of decision making, taking into account the conscious-subconscious duality, uses the framework of functional analysis in Hilbert spaces, similarly to that used in the quantum theory of measurements. This does not imply that the brain is a quantum system, but just allows for the simplest and most general extension of classical decision theory. The resulting theory of quantum decision making, based on the rules of quantum measurements, solves all paradoxes of classical decision making, allowing for quantitative predictions that are in excellent agreement with experiments. Finally, we provide a novel application by comparing the predictions of QDT with experiments on the prisoner dilemma game. The developed theory can serve as a guide for creating artificial intelligence acting by quantum rules.Comment: Latex file, 20 pages, 3 figure

Quantum phase transitions from topology in momentum space

Many quantum condensed matter systems are strongly correlated and strongly interacting fermionic systems, which cannot be treated perturbatively. However, physics which emerges in the low-energy corner does not depend on the complicated details of the system and is relatively simple. It is determined by the nodes in the fermionic spectrum, which are protected by topology in momentum space (in some cases, in combination with the vacuum symmetry). Close to the nodes the behavior of the system becomes universal; and the universality classes are determined by the toplogical invariants in momentum space. When one changes the parameters of the system, the transitions are expected to occur between the vacua with the same symmetry but which belong to different universality classes. Different types of quantum phase transitions governed by topology in momentum space are discussed in this Chapter. They involve Fermi surfaces, Fermi points, Fermi lines, and also the topological transitions between the fully gapped states. The consideration based on the momentum space topology of the Green's function is general and is applicable to the vacua of relativistic quantum fields. This is illustrated by the possible quantum phase transition governed by topology of nodes in the spectrum of elementary particles of Standard Model.Comment: 45 pages, 17 figures, 83 references, Chapter for the book "Quantum Simulations via Analogues: From Phase Transitions to Black Holes", to appear in Springer lecture notes in physics (LNP

Recent Developments in Understanding Two-dimensional Turbulence and the Nastrom-Gage Spectrum

Two-dimensional turbulence appears to be a more formidable problem than three-dimensional turbulence despite the numerical advantage of working with one less dimension. In the present paper we review recent numerical investigations of the phenomenology of two-dimensional turbulence as well as recent theoretical breakthroughs by various leading researchers. We also review efforts to reconcile the observed energy spectrum of the atmosphere (the spectrum) with the predictions of two-dimensional turbulence and quasi-geostrophic turbulence.Comment: Invited review; accepted by J. Low Temp. Phys.; Proceedings for Warwick Turbulence Symposium Workshop on Universal features in turbulence: from quantum to cosmological scales, 200

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results