Detection of sequential polyubiquitylation on a millisecond timescale

The pathway by which ubiquitin chains are generated on substrate through a cascade of enzymes consisting of an E1, E2 and E3 remains unclear. Multiple distinct models involving chain assembly on E2 or substrate have been proposed. However, the speed and complexity of the reaction have precluded direct experimental tests to distinguish between potential pathways. Here we introduce new theoretical and experimental methodologies to address both limitations. A quantitative framework based on product distribution predicts that the really interesting new gene (RING) E3 enzymes SCF^(Cdc4) and SCF^(β-TrCP) work with the E2 Cdc34 to build polyubiquitin chains on substrates by sequential transfers of single ubiquitins. Measurements with millisecond time resolution directly demonstrate that substrate polyubiquitylation proceeds sequentially. Our results present an unprecedented glimpse into the mechanism of RING ubiquitin ligases and illuminate the quantitative parameters that underlie the rate and pattern of ubiquitin chain assembly

SU(2)-in-SU(1,1) Nested Interferometer for Highly Sensitive, Loss-Tolerant Quantum Metrology

We present experimental and theoretical results on a new interferometer topology that nests a SU(2) interferometer, e.g., a Mach-Zehnder or Michelson interferometer, inside a SU(1,1) interferometer, i.e., a Mach-Zehnder interferometer with parametric amplifiers in place of beam splitters. This SU(2)-in-SU(1,1) nested interferometer (SISNI) simultaneously achieves high signal-to-noise ratio (SNR), sensitivity beyond the standard quantum limit (SQL) and tolerance to photon losses external to the interferometer, e.g., in detectors. We implement a SISNI using parametric amplification by four-wave mixing (FWM) in Rb vapor and a laser-fed Mach-Zehnder SU(2) interferometer. We observe path-length sensitivity with SNR 2.2 dB beyond the SQL at power levels (and thus SNR) 2 orders of magnitude beyond those of previous loss-tolerant interferometers. We find experimentally the optimal FWM gains and find agreement with a minimal quantum noise model for the FWM process. The results suggest ways to boost the in-practice sensitivity of high-power interferometers, e.g., gravitational wave interferometers, and may enable high-sensitivity, quantum-enhanced interferometry at wavelengths for which efficient detectors are not available.Comment: 6 pages + 4 of supplemental material, 5 figure

Make or buy – a new look for derivative action costs in Chinese law for a more enabling environment

Derivative actions in modern company law play a crucial role in protecting shareholders and promoting the soundness of corporate governance. However, since China's inauguration of derivative action there have been complications surrounding cost-related issues, especially for joint stock limited liability companies. This article focuses on a key element of the derivative action mechanism in China, namely the litigation fee. Despite the fact that fee related issues have been addressed in the recent Provisions of the Supreme People’s Court on Some Issues about the Application of the Company Law of the People's Republic of China (IV), the provisions failed to address some important aspects in detail, especially in relation to a more effective system for the filing and attorneys' fees. In order to maximize the effectiveness of derivative action and help the mechanism reach its full potential, it is crucial to make sure that litigation costs are tailored to a level that does not discourage shareholders from bringing these actions. This article aims to address the following related questions: are current fee-oriented stipulations in China hindering the effectiveness of derivative action? If so, could Chinese Company Law learn from legislative experiences from the UK, the US, and Japan to address the problem of insufficient incentives for shareholders to bring derivative actions? Through doctrinal and comparative analysis, we will explore the possibilities of establishing a more effective approach unique to China, considering its shareholding structure, corporate law, juridical system, culture, history, legal profession, and professional ethics. A fixed filing fee approach and a contingency fee arrangement supported by a common fund and substantial tests are proposed

Large deformation of spherical vesicle studied by perturbation theory and Surface evolver

With tangent angle perturbation approach the axial symmetry deformation of a spherical vesicle in large under the pressure changes is studied by the elasticity theory of Helfrich spontaneous curvature model.Three main results in axial symmetry shape: biconcave shape, peanut shape, and one type of myelin are obtained. These axial symmetry morphology deformations are in agreement with those observed in lipsome experiments by dark-field light microscopy [Hotani, J. Mol. Biol. 178, (1984) 113] and in the red blood cell with two thin filaments (myelin) observed in living state (see, Bessis, Living Blood Cells and Their Ultrastructure, Springer-Verlag, 1973). Furthermore, the biconcave shape and peanut shape can be simulated with the help of a powerful software, Surface Evolver [Brakke, Exp. Math. 1, 141 (1992) 141], in which the spontaneous curvature can be easy taken into account.Comment: 16 pages, 6 EPS figures and 2 PS figure

Spheres and Prolate and Oblate Ellipsoids from an Analytical Solution of Spontaneous Curvature Fluid Membrane Model

An analytic solution for Helfrich spontaneous curvature membrane model (H. Naito, M.Okuda and Ou-Yang Zhong-Can, Phys. Rev. E {\bf 48}, 2304 (1993); {\bf 54}, 2816 (1996)), which has a conspicuous feature of representing the circular biconcave shape, is studied. Results show that the solution in fact describes a family of shapes, which can be classified as: i) the flat plane (trivial case), ii) the sphere, iii) the prolate ellipsoid, iv) the capped cylinder, v) the oblate ellipsoid, vi) the circular biconcave shape, vii) the self-intersecting inverted circular biconcave shape, and viii) the self-intersecting nodoidlike cylinder. Among the closed shapes (ii)-(vii), a circular biconcave shape is the one with the minimum of local curvature energy.Comment: 11 pages, 11 figures. Phys. Rev. E (to appear in Sept. 1999

Area-Constrained Planar Elastica

We determine the equilibria of a rigid loop in the plane, subject to the constraints of fixed length and fixed enclosed area. Rigidity is characterized by an energy functional quadratic in the curvature of the loop. We find that the area constraint gives rise to equilibria with remarkable geometrical properties: not only can the Euler-Lagrange equation be integrated to provide a quadrature for the curvature but, in addition, the embedding itself can be expressed as a local function of the curvature. The configuration space is shown to be essentially one-dimensional, with surprisingly rich structure. Distinct branches of integer-indexed equilibria exhibit self-intersections and bifurcations -- a gallery of plots is provided to highlight these findings. Perturbations connecting equilibria are shown to satisfy a first order ODE which is readily solved. We also obtain analytical expressions for the energy as a function of the area in some limiting regimes.Comment: 23 pages, several figures. Version 2: New title. Changes in the introduction, addition of a new section with conclusions. Figure 14 corrected and one reference added. Version to appear in PR

Online Adaboost-based parameterized methods for dynamic distributed network intrusion detection

Current network intrusion detection systems lack adaptability to the frequently changing network environments. Furthermore, intrusion detection in the new distributed archi- tectures is now a major requirement. In this paper, we propose two online Adaboost-based intrusion detection algorithms. In the first algorithm, a traditional online Adaboost process is used where decision stumps are used as weak classifiers. In the second algorithm, an improved online Adaboost process is proposed, and online Gaussian mixture models (GMMs) are used as weak classifiers. We further propose a distributed intrusion detection framework, in which a local parameterized detection model is constructed in each node using the online Adaboost algorithm. A global detection model is constructed in each node by combining the local parametric models using a small number of samples in the node. This combination is achieved using an algorithm based on particle swarm optimization (PSO) and support vector ma- chines. The global model in each node is used to detect intrusions. Experimental results show that the improved online Adaboost process with GMMs obtains a higher detection rate and a lower false alarm rate than the traditional online Adaboost process that uses decision stumps. Both the algorithms outperform existing intrusion detection algorithms. It is also shown that our PSO, and SVM-based algorithm effectively combines the local detection models into the global model in each node; the global model in a node can handle the intrusion types that are found in other nodes, without sharing the samples of these intrusion types

Dynamical description of vesicle growth and shape change

We systematize and extend the description of vesicle growth and shape change using linear nonequilibrium thermodynamics. By restricting the study to shape changes from spheres to axisymmetric ellipsoids, we are able to give a consistent formulation which includes the lateral tension of the vesicle membrane. This allows us to generalize and correct a previous calculation. Our present calculations suggest that, for small growing vesicles, a prolate ellipsoidal shape should be favored over oblate ellipsoids, whereas for large growing vesicles oblates should be favored over prolates. The validity of this prediction is examined in the light of the various assumptions made in its derivation.Comment: 6 page