Dislocation theory as a physical field theory

Dislocations are the elementary carriers in many situations of plastic flow. Since they can be seen, counted and typified, e.g. in the electron microscope, and since their presence changes the state of the (elastoplastic) medium, the dislocations have the status of a physical state quantity. In spite of this a continuum theory of elastoplasticity can be built up which does not use the concept of dislocation. However, disregarding the dislocations implies approximation, and this approximation is not always good, in spite of the smallness of the dislocation diameter (order atomic distance). It is discussed how a field theory of dislocations can be developed which takes full account of the dislocational degrees of freedom.

---

Sommario In molte situazioni le dislocazioni sono i portatori puntiformi del flusso plastico. Poiché esse possono essere viste, contate e classificate, per esempio mediante il microscopio elettronico, e poiché la loro presenza cambia lo stato del mezzo (elastoplastico), le dislocazioni svolgono il ruolo di una variabile di stato. Nonostante ciò, si può formulare una teoria dell'elastoplasticità che non usa il concetto di dislocazione. Tuttavia, il trascurare le dislocazioni comporta un'approssimazione, e tale approssimazione non è sempre buona nonostante la piccolezza delle dislocazioni (dell'ordine della distanza interatomica). Si discute come si possasviluppare una teoria di campo delle dislocazione che tenga conto completo del loro grado di mobilità.

     

DNA recombination through assembly graphs

Motivated by DNA rearrangements and DNA homologous recombination modeled in [A. Angeleska, N. Jonoska, M. Saito, L.F. Landweber, RNA-guided DNA assembly, Journal of Theoretical Biology, 248(4) (2007), 706–720], we investigate smoothings on graphs that consist of only 4-valent and 1-valent rigid vertices, called assembly graphs. An assembly graph can be seen as a representation of the DNA during certain recombination processes in which 4-valent vertices correspond to the alignment of the recombination sites. A single gene is modeled by a polygonal path in an assembly graph. A polygonal path makes a “right-angle” turn at every vertex, defining smoothings at the 4-valent vertices and therefore modeling the recombination process. We investigate the minimal number of polygonal paths visiting all vertices of a given graph exactly once, and show that for every positive integer n there are graphs that require at least n such polygonal paths. We show that there is an embedding in three-dimensional space of each assembly graph such that smoothing of vertices according to a given set of polygonal paths results in an unlinked graph. As some recombination processes may happen simultaneously, we characterize the subsets of vertices whose simultaneous smoothings keep a given gene in tact and give a characterization of all sequences of sets of vertices defining successive simultaneous smoothings that can realize complete gene rearrangement.     

A marriage made in torsional space: using GALAHAD models to drive pharmacophore multiplet searches

Pharmacophore multiplets are useful tools for 3D database searching, with the queries used ordinarily being derived from ensembles of random conformations of active ligands. It seems reasonable to expect that their usefulness can be augmented by instead using queries derived from single ligand conformations obtained from aligned ligands. Comparisons of pharmacophore multiplet searching using random conformations with multiplet searching using single conformations derived from GALAHAD (a genetic algorithm with linear assignment for hypermolecular alignment of datasets) models do indeed show that, while query hypotheses based on random conformations are quite effective, hypotheses based on aligned conformations do a better job of discriminating between active and inactive compounds. In particular, the hypothesis created from a neuraminidase inhibitor model was more similar to half of 18 known actives than all but 0.2% of the compounds in a structurally diverse subset of the World Drug Index. Similarly, a model developed from five angiotensin II antagonists yielded hypotheses that placed 65 known antagonists within the top 0.1–1% of decoy databases. The differences in discriminating power ranged from 2 to 20-fold, depending on the protein target and the type of pharmacophore multiplet used.     

Development and application of hybrid structure based method for efficient screening of ligands binding to G-protein coupled receptors

G-protein coupled receptors (GPCRs) comprise a large superfamily of proteins that are targets for nearly 50% of drugs in clinical use today. In the past, the use of structure-based drug design strategies to develop better drug candidates has been severely hampered due to the absence of the receptor’s three-dimensional structure. However, with recent advances in molecular modeling techniques and better computing power, atomic level details of these receptors can be derived from computationally derived molecular models. Using information from these models coupled with experimental evidence, it has become feasible to build receptor pharmacophores. In this study, we demonstrate the use of the Hybrid Structure Based (HSB) method that can be used effectively to screen and identify prospective ligands that bind to GPCRs. Essentially; this multi-step method combines ligand-based methods for building enriched libraries of small molecules and structure-based methods for screening molecules against the GPCR target. The HSB method was validated to identify retinal and its analogues from a random dataset of ∼300,000 molecules. The results from this study showed that the 9 top-ranking molecules are indeed analogues of retinal. The method was also tested to identify analogues of dopamine binding to the dopamine D2 receptor. Six of the ten top-ranking molecules are known analogues of dopamine including a prodrug, while the other thirty-four molecules are currently being tested for their activity against all dopamine receptors. The results from both these test cases have proved that the HSB method provides a realistic solution to bridge the gap between the ever-increasing demand for new drugs to treat psychiatric disorders and the lack of efficient screening methods for GPCRs. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

The polynomial invariants of twisted links

A twisted link is a generalization of a virtual link, which is related to a link diagram on a closed, possibly non-orientable surface. In this paper we generalize the Miyazawa polynomial invariant of a virtual link to an invariant of a twisted link in two formulae one of which is introduced by A. Ishii and the other by the author.     

TE11模式增强型高效率同轴虚阴极振荡器

 在阴阳极严格同轴的条件下，理论分析表明同轴虚阴极振荡器中TE₁₁模式与TM₀₁模式与径向入射电子束的谐振耦合具有近似的作用效率。3维PIC数值模拟结果显示，即使在圆对称结构下，输出波导中非角向均匀模式在输出功率中也占有较大成分。因此，同轴虚阴极振荡器中TE11模式与电子束之间的谐振作用对器件效率的影响不可忽略。通过引入结构的不对称性以及TE11模式反射器可以抑制电子束与TM₀₁模式之间的谐振作用，从而起到抑制同轴虚阴极振荡器系统中模式竞争的作用，因此可以提高电子束到微波的功率转换效率。实验结果表明，采用阴阳极非均匀对称结构的TE₁₁模式增强型同轴虚阴极振荡器可以大幅度提高效率，在优化参数条件下获得功率转换效率约7％，输出功率大于1.0 GW的实验结果，该功率约为近似严格同轴结构的2.5倍。该研究结果可以为高效率同轴虚阴极振荡器装置设计与实验结果分析提供基本理论依据以及参数确定基础。     

轴向提取矩形波导TE10模虚阴极振荡器

 轴向提取矩形波导TE₁₀模虚阴极振荡器可以不需要模式转换器或弯曲过渡波导而直接通过天线轴向辐射微波，从而使微波源及其辐射系统更加紧凑。粒子模拟结果表明，在400 keV，8.9 kA的束流条件下，轴向提取矩形波导TE₁₀模虚阴极振荡器在2.12 GHz处可以获得功率为500 MW的高功率微波输出，功率效率为14%，频率、模式纯净。这些结果为相同波段同类装置的小型化提供了一条可能的技术途径。     

Voltammetry as a Virtual Potentiometric Sensor in Modeling of a Metal‐Ligand System and Refinement of Stability Constants. Part 1. Polarographic and Glass Electrode Potentiometric Study of a Dynamic Cd‐Glycine System

A mathematical conversion of data coming from nonequilibrium and dynamic voltammetric techniques (a direct current sampled (DC) and differential pulse (DP) polarography) into potentiometric sensor type of data is described and tested on a dynamic metal‐ligand system. A combined experiment involving DCP, DPP and glass electrode potentiometry (GEP) was performed on a single solution sample containing a fixed [L_T] : [M_T] ratio (acid‐base titration). Dedicated potentiometric software ESTA was successfully employed in the refinement operations performed on virtual potentiometric (VP) data obtained from DC and DP polarography. It was possible to refine stability constants either separately, from VP‐DC or VP‐DP, or simultaneously from any combination of VP‐DC, VP‐DP and GEP. The concept of VP‐DC or VP‐DP is reported for the first time and numerous documented and possible advantages are discussed. The proposed procedure can be easily utilized also by nonelectrochemists who are interested in, e.g., the ligand design strategies.     

Virtual Screening and Structure Generation Applied to Drug Design

The methods of computer-aided drug design can be divided into two categories according to whether or not the structures of receptors are known1, corresponding to two principal strategies: (1) searching the bio-active ligands against virtual combinatorial libraries and calculating the affinity energy between ligand and receptor by docking ; (2) QSAR and 3D-structure data-mining. 3D-QSAR method is now applied widely to drug discovery, but this method is generally limited to refine the structu…