The PDZ Domain as a Complex Adaptive System

Specific protein associations define the wiring of protein interaction networks and thus control the organization and functioning of the cell as a whole. Peptide recognition by PDZ and other protein interaction domains represents one of the best-studied classes of specific protein associations. However, a mechanistic understanding of the relationship between selectivity and promiscuity commonly observed in the interactions mediated by peptide recognition modules as well as its functional meaning remain elusive. To address these questions in a comprehensive manner, two large populations of artificial and natural peptide ligands of six archetypal PDZ domains from the synaptic proteins PSD95 and SAP97 were generated by target-assisted iterative screening (TAIS) of combinatorial peptide libraries and by synthesis of proteomic fragments, correspondingly. A comparative statistical analysis of affinity-ranked artificial and natural ligands yielded a comprehensive picture of known and novel PDZ ligand specificity determinants, revealing a hitherto unappreciated combination of specificity and adaptive plasticity inherent to PDZ domain recognition. We propose a reconceptualization of the PDZ domain in terms of a complex adaptive system representing a flexible compromise between the rigid order of exquisite specificity and the chaos of unselective promiscuity, which has evolved to mediate two mutually contradictory properties required of such higher order sub-cellular organizations as synapses, cell junctions, and others – organizational structure and organizational plasticity/adaptability. The generalization of this reconceptualization in regard to other protein interaction modules and specific protein associations is consistent with the image of the cell as a complex adaptive macromolecular system as opposed to clockwork

Dynamic redistribution of the electric field of the channel in AlGaN/GaN high electron mobility transistor with nanometer-scale gate length

Transport peculiarities and the physical origin of noise properties in AlGaN/GaN-based high electron mobility transistors (HEMTs) with a large ratio of channel length to gate length were investigated. Dependence of deviations of low-frequency noise spectra from the 1/f law on applied gate voltages was studied in an extended range of frequencies. The behavior is explained in terms of a model based on the dynamic redistribution of the electric field along the two-dimensional channel of the HEMT. The results show that the main contribution to the noise originates from the region under the gate and adjacent to the gate channel regions. (C) 2005 American Institute of Physics

Detection of several daemon populations in Earth-crossing orbits

Detection of negative daemons, DArk Electric Matter Objects, viz. Planckian supermassive (~2*10^-5 g) particles, whose population has been detected in March 2000 to populate near-Earth, almost circular, heliocentric orbits (NEACHOs), is being continued. The NEACHO objects hit the Earth with a velocity ~10-15 km/s. The results of these and new experiments (April-June, 2001) are now processed taking into account the scintillation shape depending on the magnitude and sign of the velocity of the daemons crossing our detector. The data accumulated during the time of the experiment and processed in this way reveal also the presence of (1) a high-velocity (~35-50 km/s) daemon population whose objects can be related to a population in the Galactic disk and/or that in strongly elongated, Earth-crossing heliocentric orbits (SEECHOs), as well as (2) a low-velocity (~3-10 km/s) population in geocentric Earth-surface-crossing orbits (GESCOs), whose objects traverse repeatedly the Earth to suffer a decrease in velocity by ~30-40% in a month in the process. An evolutionary relation between all these three (four?) populations is discussed. Assumptions concerning their manifestations in further observations are put forward. An analysis of possible interaction processes of daemons, which may have different velocities and directions of motion, with the detector components [ZnS(Ag) layers, 0.3-mm thick tinned-iron sheets etc.] on the atomic (emission of Auger electrons) and nuclear (nucleon evaporation from a nucleus excited in the capture and, subsequently, the decay of its protons) levels has permitted estimation of some characteristic times. In particular, the decay time of a daemon-containing proton is ~10^-6 s.Comment: 17 pages in PDF format. Ioffe Physical-Technical Institute preprint No.1753 (July 10, 2001). The work was presented at the All-Russian Astronomical Conference, August 6-12, 2001, St.Petersburg, Russi

Numerical Simulation of Vortex Crystals and Merging in N-Point Vortex Systems with Circular Boundary

In two-dimensional (2D) inviscid incompressible flow, low background vorticity distribution accelerates intense vortices (clumps) to merge each other and to array in the symmetric pattern which is called ``vortex crystals''; they are observed in the experiments on pure electron plasma and the simulations of Euler fluid. Vortex merger is thought to be a result of negative ``temperature'' introduced by L. Onsager. Slight difference in the initial distribution from this leads to ``vortex crystals''. We study these phenomena by examining N-point vortex systems governed by the Hamilton equations of motion. First, we study a three-point vortex system without background distribution. It is known that a N-point vortex system with boundary exhibits chaotic behavior for N\geq 3. In order to investigate the properties of the phase space structure of this three-point vortex system with circular boundary, we examine the Poincar\'e plot of this system. Then we show that topology of the Poincar\'e plot of this system drastically changes when the parameters, which are concerned with the sign of ``temperature'', are varied. Next, we introduce a formula for energy spectrum of a N-point vortex system with circular boundary. Further, carrying out numerical computation, we reproduce a vortex crystal and a vortex merger in a few hundred point vortices system. We confirm that the energy of vortices is transferred from the clumps to the background in the course of vortex crystallization. In the vortex merging process, we numerically calculate the energy spectrum introduced above and confirm that it behaves as k^{-\alpha},(\alpha\approx 2.2-2.8) at the region 10^0<k<10^1 after the merging.Comment: 30 pages, 11 figures. to be published in Journal of Physical Society of Japan Vol.74 No.

QUANTUM-CHEMICAL MODELING OF F+ CENTER IN OXIDES OF Mg, Ca AND Li

Presented work is devoted to theoretical investigation of F+ centers in MgO, CaO, Li2O cubic crystals. We additionally focused on effect of hybrid functional exact exchange fraction on results reliability. Our study is based on ab-initio calculations performed in CRYSTAL09[1] package using Hartree-Fock (HF) approximation and density functional theory (B3LYP[2,3]). Results as to optical absorption of F+ center, surroundings relaxation and charge density distribution were obtained

Contemporary aspects of diagnostics and treatment of mitochondrial diseases

Mitochondrial diseases caused by disturbances of structure or function of mitochondria due to mtDNA or nDNA mutations. Phenotypically, its’ manifest themselves quite variable, thus makes it difficult to its’ diagnostics. Treatment of mitochondrial diseases is pathogenetic and symptomatic with energotropic medicines, diets, physical activity. There is no aetiotropic therapy of that group of diseases.Митохондриальные заболевания обусловлены нарушениями структуры или функции митохондрий вследствие мутаций мтДНК или яДНК. Фенотипически они проявляются достаточно вариабельно, что затрудняет их диагностику. Лечение митохондриальных заболеваний патогенетическое и симптоматическое с помощью энерготропных препаратов, диет, физических нагрузок. Этиотропной терапии данной группы заболеваний не существуе

Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems

A generic mechanism - networked buffering - is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which localized decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effects cause enhanced robustness of system traits. The conditions needed for networked buffering to occur are neither demanding nor rare, supporting the conjecture that degeneracy may fundamentally underpin distributed robustness within several biotic and abiotic systems. For instance, networked buffering offers new insights into systems engineering and planning activities that occur under high uncertainty. It may also help explain recent developments in understanding the origins of resilience within complex ecosystems. \ud \u

The self-organizing fractal theory as a universal discovery method: the phenomenon of life

A universal discovery method potentially applicable to all disciplines studying organizational phenomena has been developed. This method takes advantage of a new form of global symmetry, namely, scale-invariance of self-organizational dynamics of energy/matter at all levels of organizational hierarchy, from elementary particles through cells and organisms to the Universe as a whole. The method is based on an alternative conceptualization of physical reality postulating that the energy/matter comprising the Universe is far from equilibrium, that it exists as a flow, and that it develops via self-organization in accordance with the empirical laws of nonequilibrium thermodynamics. It is postulated that the energy/matter flowing through and comprising the Universe evolves as a multiscale, self-similar structure-process, i.e., as a self-organizing fractal. This means that certain organizational structures and processes are scale-invariant and are reproduced at all levels of the organizational hierarchy. Being a form of symmetry, scale-invariance naturally lends itself to a new discovery method that allows for the deduction of missing information by comparing scale-invariant organizational patterns across different levels of the organizational hierarchy