Glioblastoma-Specific Protein Interaction Network Identifies PP1A and CSK21 as Connecting Molecules between Cell Cycle-Associated Genes

Glioblastoma (GBM; grade IV astrocytoma) is a very aggressive form of brain cancer with a poor survival and few qualified predictive markers. This study integrates experimentally validated genes that showed specific upregulation in GBM along with their protein-protein interaction information. A system level analysis was used to construct GBM-specific network. Computation of topological parameters of networks showed scale-free pattern and hierarchical organization. From the large network involving 1,447 proteins, we synthesized subnetworks and annotated them with highly enriched biological processes. A careful dissection of the functional modules, important nodes, and their connections identified two novel intermediary molecules CSK21 and protein phosphatase 1 alpha (PP1A) connecting the two subnetworks CDC2-PTEN-TOP2A-CAV1-P53 and CDC2-CAV1-RB-P53-PTEN, respectively. Real-time quantitative reverse transcription-PCR analysis revealed CSK21 to be moderately upregulated and PP1A to be overexpressed by 20-fold in GBM tumor samples. Immunohistochemical staining revealed nuclear expression of PP1A only in GBM samples. Thus, CSK21 and PP1A, whose functions are intimately associated with cell cycle regulation, might play key role in gliomagenesis. Cancer Res; 70(16); 6437-47. (C)2010 AACR.

Partially conserved axial-vector current inS-matrix theory

Mandelstam�s argument that PCAC follows from assigning Lorentz quantum numberM=1 to the massless pion is examined in the context of multiparticle dual resonance model. We construct a factorisable dual model for pions which is formulated operatorially on the harmonic oscillator Fock space along the lines of Neveu-Schwarz model. The model has bothm ? andm ? as arbitrary parameters unconstrained by the duality requirement. Adler self-consistency condition is satisfied if and only if the conditionm?2?m?2=1/2 is imposed, in which case the model reduces to the chiral dual pion model of Neveu and Thorn, and Schwarz. The Lorentz quantum number of the pion in the dual model is shown to beM=0.

PeptideMine - A webserver for the design of peptides for protein-peptide binding studies derived from protein-protein interactomes

Background: Signal transduction events often involve transient, yet specific, interactions between structurally conserved protein domains and polypeptide sequences in target proteins. The identification and validation of these associating domains is crucial to understand signal transduction pathways that modulate different cellular or developmental processes. Bioinformatics strategies to extract and integrate information from diverse sources have been shown to facilitate the experimental design to understand complex biological events. These methods, primarily based on information from high-throughput experiments, have also led to the identification of new connections thus providing hypothetical models for cellular events. Such models, in turn, provide a framework for directing experimental efforts for validating the predicted molecular rationale for complex cellular processes. In this context, it is envisaged that the rational design of peptides for protein-peptide binding studies could substantially facilitate the experimental strategies to evaluate a predicted interaction. This rational design procedure involves the integration of protein-protein interaction data, gene ontology, physico-chemical calculations, domain-domain interaction data and information on functional sites or critical residues. Results: Here we describe an integrated approach called ``PeptideMine'' for the identification of peptides based on specific functional patterns present in the sequence of an interacting protein. This approach based on sequence searches in the interacting sequence space has been developed into a webserver, which can be used for the identification and analysis of peptides, peptide homologues or functional patterns from the interacting sequence space of a protein. To further facilitate experimental validation, the PeptideMine webserver also provides a list of physico-chemical parameters corresponding to the peptide to determine the feasibility of using the peptide for in vitro biochemical or biophysical studies. Conclusions: The strategy described here involves the integration of data and tools to identify potential interacting partners for a protein and design criteria for peptides based on desired biochemical properties. Alongside the search for interacting protein sequences using three different search programs, the server also provides the biochemical characteristics of candidate peptides to prune peptide sequences based on features that are most suited for a given experiment. The PeptideMine server is available at the URL: http://caps.ncbs.res.in/peptidemine

Strong spin-two interaction and general relativity

The concept of short range strong spin-two (f) field (mediated by massive f-mesons) and interacting directly with hadrons was introduced along with the infinite range (g) field in early seventies. In the present review of this growing area (often referred to as strong gravity) we give a general relativistic treatment in terms of Einstein-type (non-abelian gauge) field equations with a coupling constant Gf reverse similar, equals 1038 GN (GN being the Newtonian constant) and a cosmological term λf ƒ;μν (ƒ;μν is strong gravity metric and λf not, vert, similar 1028 cm− is related to the f-meson mass). The solutions of field equations linearized over de Sitter (uniformly curves) background are capable of having connections with internal symmetries of hadrons and yielding mass formulae of SU(3) or SU(6) type. The hadrons emerge as de Sitter “microuniverses” intensely curved within (radius of curvature not, vert, similar10−14 cm).The study of spinor fields in the context of strong gravity has led to Heisenberg's non-linear spinor equation with a fundamental length not, vert, similar2 × 10−14 cm. Furthermore, one finds repulsive spin-spin interaction when two identical spin-Image particles are in parallel configuration and a connection between weak interaction and strong gravity.Various other consequences of strong gravity embrace black hole (solitonic) solutions representing hadronic bags with possible quark confinement, Regge-like relations between spins and masses, connection with monopoles and dyons, quantum geons and friedmons, hadronic temperature, prevention of gravitational singularities, providing a physical basis for Dirac's two metric and large numbers hypothesis and projected unification with other basic interactions through extended supergravity.

Maturation of a transient outward potassium current in mouse fetal hypothalamic neurons in culture

The whole-cell voltage clamp technique was used to record potassium currents in mouse fetal hypothalamic neurons developing in culture medium from days 1 to 17. The neurons were derived from fetuses of IOPS/OF1 mice on the 14th day of gestation. The mature neurons (>six days in culture) showed both a transient potassium current and a non-inactivating delayed rectifier potassium current. These were identified pharmacologically by using the potassium channel blockers tetraethyl ammonium chloride and 4-aminopyridine, and on the basis of their kinetics and voltage sensitivities. The delayed rectifier potassium current had a threshold of −20 mV, a slow time-course of activation, and was sustained during the voltage pulse. The 4-aminopyridine-sensitive current was transient, and was activated from a holding potential more negative (−80 mV) than that required for evoking the delayed rectifier potassium current (−40 mV). The delayed rectifier potassium current was detectable from day 1 onwards, while the transient potassium current showed a distinct developmental trend. The time-constant of inactivation became faster with age in culture. The half steady-state inactivation potential showed a shift towards less negative membrane potentials with age, and the relationship was best described by a logarithmic regression equation.The developmental trend of the transient potassium current may relate functionally to the progressive morphological changes, and the appearance of synaptic connections during ontogenesis.

Uniformly accelerated observer in Moyal spacetime

In Minkowski space, an accelerated reference frame may be defined as one that is related to an inertial frame by a sequence of instantaneous Lorentz transformations. Such an accelerated observer sees a causal horizon, and the quantum vacuum of the inertial observer appears thermal to the accelerated observer, also known as the Unruh effect. We argue that an accelerating frame may be similarly defined (i.e. as a sequence of instantaneous Lorentz transformations) in noncommutative Moyal spacetime, and discuss the twisted quantum field theory appropriate for such an accelerated observer. Our analysis shows that there are several new features in the case of noncommutative spacetime: chiral massless fields in (1 + 1) dimensions have a qualitatively different behavior compared to massive fields. In addition, the vacuum of the inertial observer is no longer an equilibrium thermal state of the accelerating observer, and the Bose-Einstein distribution acquires.-dependent corrections.

Interaction Energy Based Protein Structure Networks

The three dimensional structure of a protein is formed and maintained by the noncovalent interactions among the amino acid residues of the polypeptide chain These interactions can be represented collectively in the form of a network So far such networks have been investigated by considering the connections based on distances between the amino acid residues Here we present a method of constructing the structure network based on interaction energies among the amino acid residues in the protein We have investigated the properties of such protein energy based networks (PENs) and have shown correlations to protein structural features such as the clusters of residues involved in stability formation of secondary and super secondary structural units Further we demonstrate that the analysis of PENs in terms of parameters such as hubs and shortest paths can provide a variety of biologically important information such as the residues crucial for stabilizing the folded units and the paths of communication between distal residues in the protein Finally the energy regimes for different levels of stabilization in the protein structure have clearly emerged from the PEN analysis

Euclideanization, topological theories, higher dimensions and all that

It is shown that the euclideanized Yukawa theory, with the Dirac fermion belonging to an irreducible representation of the Lorentz group, is not bounded from below. A one parameter family of supersymmetric actions is presented which continuously interpolates between the N = 2 SSYM and the N = 2 supersymmetric topological theory. In order to obtain a theory which is bounded from below and satisfies Osterwalder-Schrader positivity, the Dirac fermion should belong to a reducible representation of the Lorentz group and the scalar fields have to be reinterpreted as the extra components of a higher dimensional vector field.

Some experiments on human memory and a new neural model

An associative memory with parallel architecture is presented. The neurons are modelled by perceptrons having only binary, rather than continuous valued input. To store m elements each having n features, m neurons each with n connections are needed. The n features are coded as an n-bit binary vector. The weights of the n connections that store the n features of an element has only two values -1 and 1 corresponding to the absence or presence of a feature. This makes the learning very simple and straightforward. For an input corrupted by binary noise, the associative memory indicates the element that is closest (in terms of Hamming distance) to the noisy input. In the case where the noisy input is equidistant from two or more stored vectors, the associative memory indicates two or more elements simultaneously. From some simple experiments performed on the human memory and also on the associative memory, it can be concluded that the associative memory presented in this paper is in some respect more akin to a human memory than a Hopfield model.

Variable Elimination in Linear Constraints

Gauss and Fourier have together provided us with the essential techniques for symbolic computation with linear arithmetic constraints over the reals and the rationals. These variable elimination techniques for linear constraints have particular significance in the context of constraint logic programming languages that have been developed in recent years. Variable elimination in linear equations (Guassian Elimination) is a fundamental technique in computational linear algebra and is therefore quite familiar to most of us. Elimination in linear inequalities (Fourier Elimination), on the other hand, is intimately related to polyhedral theory and aspects of linear programming that are not quite as familiar. In addition, the high complexity of elimination in inequalities has forces the consideration of intricate specializations of Fourier's original method. The intent of this survey article is to acquaint the reader with these connections and developments. The latter part of the article dwells on the thesis that variable elimination in linear constraints over the reals extends quite naturally to constraints in certain discrete domains.

The effect of traffic shaping in efficiently providing end-to-end performance guarantees

This paper reports new results concerning the capabilities of a family of service disciplines aimed at providing per-connection end-to-end delay (and throughput) guarantees in high-speed networks. This family consists of the class of rate-controlled service disciplines, in which traffic from a connection is reshaped to conform to specific traffic characteristics, at every hop on its path. When used together with a scheduling policy at each node, this reshaping enables the network to provide end-to-end delay guarantees to individual connections. The main advantages of this family of service disciplines are their implementation simplicity and flexibility. On the other hand, because the delay guarantees provided are based on summing worst case delays at each node, it has also been argued that the resulting bounds are very conservative which may more than offset the benefits. In particular, other service disciplines such as those based on Fair Queueing or Generalized Processor Sharing (GPS), have been shown to provide much tighter delay bounds. As a result, these disciplines, although more complex from an implementation point-of-view, have been considered for the purpose of providing end-to-end guarantees in high-speed networks. In this paper, we show that through ''proper'' selection of the reshaping to which we subject the traffic of a connection, the penalty incurred by computing end-to-end delay bounds based on worst cases at each node can be alleviated. Specifically, we show how rate-controlled service disciplines can be designed to outperform the Rate Proportional Processor Sharing (RPPS) service discipline. Based on these findings, we believe that rate-controlled service disciplines provide a very powerful and practical solution to the problem of providing end-to-end guarantees in high-speed networks.

Queuing strategies for qos management of traffic between lans interconnected by low-speed wan links

We provide a comparative performance evaluation of packet queuing and link admission strategies for low-speed wide area network Links (e.g. 9600 bps, 64 kbps) that interconnect relatively highspeed, connectionless local area networks (e.g. 10 Mbps). In particular, we are concerned with the problem of providing differential quality of service to interLAN remote terminal and file transfer sessions, and throughput fairness between interLAN file transfer sessions. We use analytical and simulation models to study a variety of strategies. Our work also serves to address the performance comparison of connectionless vs. connection-oriented interconnection of CLNS LANS. When provision of priority at the physical transmission level is not feasible, we show, for low-speed WAN links (e.g. 9600 bps), the superiority of connection-oriented interconnection of connectionless LANs, with segregation of traffic streams with different QoS requirements into different window flow controlled connections. Such an implementation can easily be obtained by transporting IP packets over an X.25 WAN. For 64 kbps WAN links, there is a drop in file transfer throughputs, owing to connection overheads, but the other advantages are retained, The same solution also helps to provide throughput fairness between interLAN file transfer sessions. We also provide a corroboration of some of our modelling results with results from an experimental test-bed.

On the problem of spurious patterns in neural associative memory models

The problem of spurious patterns in neural associative memory models is discussed, Some suggestions to solve this problem from the literature are reviewed and their inadequacies are pointed out, A solution based on the notion of neural self-interaction with a suitably chosen magnitude is presented for the Hebb learning rule. For an optimal learning rule based on linear programming, asymmetric dilution of synaptic connections is presented as another solution to the problem of spurious patterns, With varying percentages of asymmetric dilution it is demonstrated numerically that this optimal learning rule leads to near total suppression of spurious patterns. For practical usage of neural associative memory networks a combination of the two solutions with the optimal learning rule is recommended to be the best proposition.

The 2D Coulomb gas on a 1D lattice

The statistical mechanics of a two-dimensional Coulomb gas confined to one dimension is studied, wherein hard core particles move on a ring. Exact self-duality is shown for a version of the sine-Gordon model arising in this context, thereby locating the transition temperature exactly. We present asymptotically exact results for the correlations in the model and characterize the low- and high-temperature phases. Numerical simulations provide support to these renormalization group calculations. Connections with other interesting problems, such as the quantum Brownian motion of a panicle in a periodic potential and impurity problems, are pointed out.

Topological phases, Majorana modes and quench dynamics in a spin ladder system

We explore the salient features of the `Kitaev ladder', a two-legged ladder version of the spin-1/2 Kitaev model on a honeycomb lattice, by mapping it to a one-dimensional fermionic p-wave superconducting system. We examine the connections between spin phases and topologically non-trivial phases of non-interacting fermionic systems, demonstrating the equivalence between the spontaneous breaking of global Z(2) symmetry in spin systems and the existence of isolated Majorana modes. In the Kitaev ladder, we investigate topological properties of the system in different sectors characterized by the presence or absence of a vortex in each plaquette of the ladder. We show that vortex patterns can yield a rich parameter space for tuning into topologically non-trivial phases. We introduce and employ a new topological invariant for explicitly determining the presence of zero energy Majorana modes at the boundaries of such phases. Finally, we discuss dynamic quenching between topologically non-trivial phases in the Kitaev ladder and, in particular, the post-quench dynamics governed by tuning through a quantum critical point.