A Mouse with a Loss-of-function Mutation in the c-Cbl TKB Domain Shows Perturbed Thymocyte Signaling without Enhancing the Activity of the ZAP-70 Tyrosine Kinase

The unique tyrosine kinase binding (TKB) domain of Cbl targets phosphorylated tyrosines on activated protein tyrosine kinases (PTKs); this targeting is considered essential for Cbl proteins to negatively regulate PTKs. Here, a loss-of-function mutation (G304E) in the c-Cbl TKB domain, first identified in Caenorhabditis elegans, was introduced into a mouse and its effects in thymocytes and T cells were studied. In marked contrast to the c-Cbl knockout mouse, we found no evidence of enhanced activity of the ZAP-70 PTK in thymocytes from the TKB domain mutant mouse. This finding contradicts the accepted mechanism of c-Cbl–mediated negative regulation, which requires TKB domain targeting of phosphotyrosine 292 in ZAP-70. However, the TKB domain mutant mouse does show aspects of enhanced signaling that parallel those of the c-Cbl knockout mouse, but these involve the constitutive activation of Rac and not enhanced PTK activity. Furthermore, the enhanced signaling in CD4+CD8+ double positive thymocytes appears to be compensated by the selective down-regulation of CD3 on mature thymocytes and peripheral T cells from both strains of mutant c-Cbl mice

Exhaustive enumeration unveils clustering and freezing in random 3-SAT

We study geometrical properties of the complete set of solutions of the random 3-satisfiability problem. We show that even for moderate system sizes the number of clusters corresponds surprisingly well with the theoretic asymptotic prediction. We locate the freezing transition in the space of solutions which has been conjectured to be relevant in explaining the onset of computational hardness in random constraint satisfaction problems.Comment: 4 pages, 3 figure

Exact half-BPS Type IIB interface solutions I: Local solution and supersymmetric Janus

The complete Type IIB supergravity solutions with 16 supersymmetries are obtained on the manifold $AdS_4 \times S^2 \times S^2 \times \Sigma$ with $SO(2,3) \times SO(3) \times SO(3)$ symmetry in terms of two holomorphic functions on a Riemann surface $\Sigma$, which generally has a boundary. This is achieved by reducing the BPS equations using the above symmetry requirements, proving that all solutions of the BPS equations solve the full Type IIB supergravity field equations, mapping the BPS equations onto a new integrable system akin to the Liouville and Sine-Gordon theories, and mapping this integrable system to a linear equation which can be solved exactly. Amongst the infinite class of solutions, a non-singular Janus solution is identified which provides the AdS/CFT dual of the maximally supersymmetric Yang-Mills interface theory discovered recently. The construction of general classes of globally non-singular solutions, including fully back-reacted $AdS_5 \times S^5$ and supersymmetric Janus doped with D5 and/or NS5 branes, is deferred to a companion paper.Comment: LaTeX, 69 pages, 3 figures, v2: references adde

Rescue of skeletal muscle α-actin–null mice by cardiac (fetal) α-actin

Skeletal muscle α-actin (ACTA1) is the major actin in postnatal skeletal muscle. Mutations of ACTA1 cause mostly fatal congenital myopathies. Cardiac α-actin (ACTC) is the major striated actin in adult heart and fetal skeletal muscle. It is unknown why ACTC and ACTA1 expression switch during development. We investigated whether ACTC can replace ACTA1 in postnatal skeletal muscle. Two ACTC transgenic mouse lines were crossed with Acta1 knockout mice (which all die by 9 d after birth). Offspring resulting from the cross with the high expressing line survive to old age, and their skeletal muscles show no gross pathological features. The mice are not impaired on grip strength, rotarod, or locomotor activity. These findings indicate that ACTC is sufficiently similar to ACTA1 to produce adequate function in postnatal skeletal muscle. This raises the prospect that ACTC reactivation might provide a therapy for ACTA1 diseases. In addition, the mouse model will allow analysis of the precise functional differences between ACTA1 and ACTC

Strongly Correlated Quantum Fluids: Ultracold Quantum Gases, Quantum Chromodynamic Plasmas, and Holographic Duality

Strongly correlated quantum fluids are phases of matter that are intrinsically quantum mechanical, and that do not have a simple description in terms of weakly interacting quasi-particles. Two systems that have recently attracted a great deal of interest are the quark-gluon plasma, a plasma of strongly interacting quarks and gluons produced in relativistic heavy ion collisions, and ultracold atomic Fermi gases, very dilute clouds of atomic gases confined in optical or magnetic traps. These systems differ by more than 20 orders of magnitude in temperature, but they were shown to exhibit very similar hydrodynamic flow. In particular, both fluids exhibit a robustly low shear viscosity to entropy density ratio which is characteristic of quantum fluids described by holographic duality, a mapping from strongly correlated quantum field theories to weakly curved higher dimensional classical gravity. This review explores the connection between these fields, and it also serves as an introduction to the Focus Issue of New Journal of Physics on Strongly Correlated Quantum Fluids: from Ultracold Quantum Gases to QCD Plasmas. The presentation is made accessible to the general physics reader and includes discussions of the latest research developments in all three areas.Comment: 138 pages, 25 figures, review associated with New Journal of Physics special issue "Focus on Strongly Correlated Quantum Fluids: from Ultracold Quantum Gases to QCD Plasmas" (http://iopscience.iop.org/1367-2630/focus/Focus%20on%20Strongly%20Correlated%20Quantum%20Fluids%20-%20from%20Ultracold%20Quantum%20Gases%20to%20QCD%20Plasmas

Janus solutions in M-theory

We present a one-parameter deformation of the AdS_{4} x S^{7} vacuum, which is a regular solution in M-theory, invariant under SO(2,2) x SO(4) x SO(4), and which preserves 16 supersymmetries. The solution corresponds to a holographic realization of a Janus-like interface/defect theory, despite the absence of a dilaton in M-theory. The 2+1-dimensional CFT dual results from the maximally symmetric CFT through the insertion of a dimension 2 operator which is localized along a 1+1-dimensional linear interface/defect, thereby partially breaking the superconformal symmetry. The solution admits a regular ABJM reduction to a quotient solution which is invariant under SO(2,2) x SO(4) x U(1)^2, preserves 12 supersymmetries, and provides a Janus-like interface/defect solution in ABJM theory.Comment: 20 pages, 2 figures, pdflate

Medical decision making for patients with Parkinson disease under Average Cost Criterion

Parkinson's disease (PD) is one of the most common disabling neurological disorders and results in substantial burden for patients, their families and the as a whole society in terms of increased health resource use and poor quality of life. For all stages of PD, medication therapy is the preferred medical treatment. The failure of medical regimes to prevent disease progression and to prevent long-term side effects has led to a resurgence of interest in surgical procedures. Partially observable Markov decision models (POMDPs) are a powerful and appropriate technique for decision making. In this paper we applied the model of POMDP's as a supportive tool to clinical decisions for the treatment of patients with Parkinson's disease. The aim of the model was to determine the critical threshold level to perform the surgery in order to minimize the total lifetime costs over a patient's lifetime (where the costs incorporate duration of life, quality of life, and monetary units). Under some reasonable conditions reflecting the practical meaning of the deterioration and based on the various diagnostic observations we find an optimal average cost policy for patients with PD with three deterioration levels