Catalytic mechanism of l,l-diaminopimelic acid with diaminopimelate epimerase by molecular docking simulations

Peptidoglycan, a key constituent of bacterial cell walls, is currently the target of broad spectrum antibiotics and a new research field involves both design and synthesis of inhibitors of its biosynthesis. Most bacteria require either lysine, or its biosynthetic precursor, diaminopimelate (meso-DAP), as a component of the peptidoglycan layer of the cell wall. In this paper, molecular modelling studies were undertaken in order to shed light on the molecular basis of interaction between (2S,6S)-diaminopimelic acid (l,l-DAP) (1) with its target enzyme DAP-epimerase, since this is a key step in the lysine biosynthetic path leading to (2R,6S)-diaminopimelic acid (meso-DAP) (2). In particular, the docking of the ligand-enzyme complex was studied by means of MD simulations and DFT computations in order to ascertain the optimal structural requirements for the epimerization reaction. Molecular dynamics simulations clearly showed that the configuration of the distal carbon C6 of l,l-DAP is critical for complex formation since both amino and carboxylate groups are involved in Hbonding interactions with the active site residues. Furthermore, the interactions occurring between the functional groups bonded to the C2 and some residues of the binding cavity immobilize the ligand in a position appropriate for the epimerization reaction, i.e., exactly in the middle of the two catalytic residues Cys73 and Cys217 as confirmed by DFT quantum mechanical computation of the Michaelis complex. All this mechanistic information could be useful for the rational design of new potential antibiotic drugs effective as inhibitors of peptidoglycan biosynthesis.     

延展表面凝结液膜的动量积分方法

采用动量积分方法分析压水堆发生失水事故时在安全壳的内表面上的液膜凝结、再浸润和蒸发过程。由凝结液膜的质量和动量守恒方程导出了凝结液膜在延展表面的子午线方向平均速度的积分-微分方程。假设液膜以层流的方式流动，把导出的积分-微分方程变成容易进行数值积分的液膜速度的一阶常微分方程，由此求得液膜厚度分布。液膜能量守恒方程的解给出了安全壳内壁面的温度分布。     

Dynamic aspects of visual modelling languages

A large class of diagrammatic languages falls under the broad definition of “executable graphics”, meaning that some transformational semantics can be devised for them. On the other hand, the definition of static aspects of visual languages often relies on some form of parsing or constructive process. We propose here an approach to the definition of visual languages syntax and semantics based on a notion of transition as production/consumption of resources. Transitions can be represented in forms which are intrinsic to the diagrams or external to them. A collection of abstract metamodels is presented to discuss the approach.     

A methodology for verification of digital items in fair exchange protocols with active trustee

Fair exchange constitutes a fundamental mechanism for electronic commerce. Fair exchange assumes that it is possible to verify the correctness of the digital items to be exchanged. However, when an item is indescribable , i.e., it cannot be formally specified, its verification becomes difficult, if not impossible. This hinders a practical deployment of fair exchange. We propose a methodology for the verification of indescribable digital items. The methodology allows a participant in a fair exchange protocol to personally verify the indescribable item without giving him any practical advantage over the other participant, and therefore without violating the fairness imposed by the protocol.     

Complexity-preserving simulations among three variants of accepting networks of evolutionary processors

In this paper we consider three variants of accepting networks of evolutionary processors. It is known that two of them are equivalent to Turing machines. We propose here a direct simulation of one device by the other. Each computational step in one model is simulated in a constant number of computational steps in the other one while a translation via Turing machines squares the time complexity. We also discuss the possibility of constructing simulations that preserve not only complexity, but also the shape of the simulated network.     

Aroyl-pyrrolyl hydroxyamides: influence of pyrrole C4-phenylacetyl substitution on histone deacetylase inhibition

The novel aroyl-pyrrolyl hydroxyamides 4 a-a' are analogues of the lead compound 3-(1-methyl-4-phenylacetyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamide (2) and are active as HDAC inhibitors. The benzene ring of 2 was substituted with a wide range of electron-donating and electron-withdrawing groups, and the effect was evaluated on three HDACs from maize, namely HD2, HD1-B (a class I HDAC), and HD1-A (a class II HDAC). Inhibition studies show that the benzene 3' and, to a lesser extent, 4' positions of 2 were the most suitable for the introduction of substituents, with the 3'-chloro (in 4 b) and the 3'-methyl (in 4 k) derivatives being the most potent compounds, reaching the same activity as SAHA. Inhibition data for 4 b,k against mouse HDAC1 were consistent with those observed in the maize enzyme. The substituent insertion on the benzene ring of 2 (compounds 4 a-a') abated the slight (3-fold) selectivity for class II HDACs displayed by 2. Compound 4 b showed interesting, dose-dependent antiproliferative and cytodifferentiation properties against human acute promyelocytic leukemia HL-60 cells.     

Progression of permanent atrial fibrillation after atrioventricular junction ablation and dual-chamber pacemaker implantation in patients with paroxysmal atrial tachyarrhythmias

Control of the house dust mite allergen has received considerable attention owing to its importance in some allergic diseases. One aspect of dust mites and their allergen-carrying faecal particles that has not been reported on, which may have allergen control applications, is the electrostatic charge they carry in the natural environment. To promote tribo-electric charging, household dust containing dust mite allergen and live house dust mites are separately agitated while in contact with either polypropylene, nylon or earthed metal. The charged dust and mites are subsequently subjected to electrostatic separation and collection. Results for concentrations of the house dust mite allergen, Der p1, indicate that, when subjected to nylon, Der p1 carrier particles appear to be predominantly positively charged. Similarly, when subjected to polypropylene, Der p1 carrier particles also appear to be positively charged. Reduction of excess free charge by agitation against earthed metal does not appear to affect the observed charging characteristics, indicating that the positive charge may be bound or inherent in the Der p1 carrier particles. In contrast, house dust mites exposed to nylon appear to be generally charging negative, whereas mites exposed to polypropylene appear to be charging positive. The observed electrostatic characteristics of the mites and Der p1 carrying particles will be useful in the future development of electrostatic allergen control methods.     

On the behaviour of the rheological and magnetic parameters of densified γ-Fe2O3

Magnetic characteristics (coercivity, remanent coercivity, remanence/saturation ratio, coercivity factor) and rheological properties (tap density, apparent density and wettability) for a number of γ-Fe2O3samples are analyzed. The samples are the following: I. γ-Fe2O3produced from densified α-FeOOH at various densification times; II. Densified γ-Fe2O3withdrawn from the densifier at different densification times; III. Densified and non-densified materials available on the market. The magnetic data as a function of the densification degree (i.e. vs. apparent density) confirm the increase of interactions and the re-assembling of the loose particles in a distribution of single particles, sheaf and ring shaped clusters. The wettability of the I samples is largely different from that of II samples; an hypothesis is made: densification produces a rough cleaning of the particles surface thus bringing out the reactive sites of the surface that can therefore be easily wetted out. Samples III confirm this hypothesis.     

Stories and signs in an e-learning environment for deaf people

An important field for model-driven development of interfaces is the consideration of users with disabilities. Interface design for deaf people presents specific problems, since it needs to be based on visual communication, incorporating unusual forms of interaction, in particular gesture-based ones. Standard solutions for model-driven development of visual interfaces lack specific constructs for structuring these more sophisticated forms of interaction. This paper discusses such issues in the context of the development of a deaf-centered e-learning environment. Sign Languages enter this context as a suitable alternative communication code, both in video form and through one of their most successful written forms, namely SignWriting.