Design,Synthesis, and in vitro Evaluation of P2X7 Antagonists

The P2X7 receptor is a promising target for the treatment of various diseases due to its significant role in inflammation and immune cell signaling. This work describes the design, synthesis, and in vitro evaluation of a series of novel derivatives bearing diverse scaffolds as potent P2X7 antagonists. Our approach was based on structural modifications of reported (adamantan-1-yl)methylbenzamides able to inhibit the receptor activation. The adamantane moieties and the amide bond were replaced, and the replacements were evaluated by a ligand-based pharmacophore model. The antagonistic potency of the synthesized analogues was assessed by two-electrode voltage clamp experiments, using Xenopus laevis oocytes that express the human P2X7 receptor. SAR studies suggested that the replacement of the adamantane ring by an aryl-cyclohexyl moiety afforded the most potent antagonists against the activation of the P2X7 cation channel, with analogue 2-chloro-N-[1-(3-(nitrooxymethyl)phenyl)cyclohexyl)methyl]benzamide ( 56 ) exhibiting the best potency with an IC₅₀ value of 0.39 μM.     

Multi-Scale Analysis of Fretting Fatigue in Heterogeneous Materials Using Computational Homogenization

This paper deals with modeling of the phenomenon of fretting fatigue in heterogeneous materials using the multi-scale computational homogenization technique and finite element analysis (FEA). The heterogeneous material for the specimens consists of a single hole model (25% void/cell, 16% void/cell and 10% void/cell) and a four-hole model (25% void/cell). Using a representative volume element (RVE), we try to produce the equivalent homogenized properties and work on a homogeneous specimen for the study of fretting fatigue. Next, the fretting fatigue contact problem is performed for 3 new cases of models that consist of a homogeneous and a heterogeneous part (single hole cell) in the contact area. The aim is to analyze the normal and shear stresses of these models and compare them with the results of the corresponding heterogeneous models based on the Direct Numerical Simulation (DNS) method. Finally, by comparing the computational time and % deviations, we draw conclusions about the reliability and effectiveness of the proposed method.     

The expansion of Google Scholar versus Web of Science: a longitudinal study

Web of Science (WoS) and Google Scholar (GS) are prominent citation services with distinct indexing mechanisms. Comprehensive knowledge about the growth patterns of these two citation services is lacking. We analyzed the development of citation counts in WoS and GS for two classic articles and 56 articles from diverse research fields, making a distinction between retroactive growth (i.e., the relative difference between citation counts up to mid-2005 measured in mid-2005 and citation counts up to mid-2005 measured in April 2013) and actual growth (i.e., the relative difference between citation counts up to mid-2005 measured in April 2013 and citation counts up to April 2013 measured in April 2013). One of the classic articles was used for a citation-by-citation analysis. Results showed that GS has substantially grown in a retroactive manner (median of 170 % across articles), especially for articles that initially had low citations counts in GS as compared to WoS. Retroactive growth of WoS was small, with a median of 2 % across articles. Actual growth percentages were moderately higher for GS than for WoS (medians of 54 vs. 41 %). The citation-by-citation analysis showed that the percentage of citations being unique in WoS was lower for more recent citations (6.8 % for citations from 1995 and later vs. 41 % for citations from before 1995), whereas the opposite was noted for GS (57 vs. 33 %). It is concluded that, since its inception, GS has shown substantial expansion, and that the majority of recent works indexed in WoS are now also retrievable via GS. A discussion is provided on quantity versus quality of citations, threats for WoS, weaknesses of GS, and implications for literature research and research evaluation.     

Selection of TBM and geotechnical assessment of a microtunnel in a difficult geological environment: a case of a natural gas pipeline beneath an active landslide (Albania)

Bulletin of Engineering Geology and the Environment - This present paper presents an adopted methodology for Micro Tunnel Boring Machine (TBM) selection, based on the results of a...     

On Supporting Secure Information Distribution in Heterogeneous Systems Using Standard Technologies

This paper presents an integrated security architecture for heterogeneous distributed systems. Based on the MPEG-21 standard data structures and the MPEG-M standard services, the proposed architecture provides a unified, fine-grained solution for protecting each information unit circulated in the system. In this context, a novel scheme for translating the access control rules, initially expressed by means of the standard MPEG-21 Rights Expression Language, into Ciphertext-Policy Attribute-Based Encryption access trees is introduced, thereby enabling offline authorization based on the users’ attributes, also encapsulated and certified using MPEG-21 licenses. The proposed framework provides a detailed approach in all the steps of the information protection process, from attribute acquisition to data encryption and decryption.     

Grip to the Colon by Means of Macroscopic Adhesion-Controlled Friction

Manipulating friction without applying high normal forces is important for an intestine inspection and intervention device in order to eliminate the risk of tissue damage. One possible solution is to generate friction by means of adhesive forces. The adhesive forces should be high to offer sufficient grip without needing high normal forces. The generated friction is then called adhesion-controlled and depends on the size of the area in contact. Adhesion-controlled friction is well known to be dominant at microscopic and molecular levels. According to this paper, adhesion-controlled friction can be applicable on the macroscopic scale as well and, more specifically, within a range of forces in which friction is usually considered to be load-controlled. The intestine inspection and intervention device manipulates the friction with the colonic wall by means of mucoadhesive films. In this way, grip with high static friction is achieved without the need to apply high normal forces and friction is altered by changing the size of the area of the mucoadhesive film. Friction theories on different scales are revisited and considered in order to understand the dominant phenomena and the principles associated with this macroscopic adhesion-controlled friction.     

Evaluating an intelligent diagnosis system of historical text comprehension

This work aims to present and evaluate a Fuzzy-Case Based Reasoning Diagnosis system of Historical Text Comprehension. The synergism of fuzzy logic and case based reasoning techniques handles the uncertainty in the acquisition of human expert's knowledge regarding learner's observable behaviour and integrates the right balance between expert's knowledge described in the form of fuzzy sets and previous experiences documented in the form of cases. The formative evaluation focused on the comparison of the system's performance to the performance of human experts concerning the diagnosis accuracy. The system was also evaluated for its behaviour when using two different historical texts. Empirical evaluation conducted with human experts and real students indicated the need for revision of the diagnosis model. The evaluation results are encouraging for the system's educational impact on learners and for future work concerning an intelligent educational system for individualized learning.     

Nitrate ion effect on the passive film breakdown and current oscillations at iron surfaces polarized in chloride-containing sulfuric acid solutions

Current oscillatory phenomena have been used to study the effect of nitrates on pitting corrosion of passive iron surfaces in chloride-containing sulfuric acid solutions. From the quasi steady-state current-potential and potentiostatic current-time curves of the Fe | 0.75 M H₂SO₄+10 mM Cl⁻ system it is deduced that at lower potentials nitrates stimulate pitting acting as activators of the oxide dissolution. At higher potentials nitrates act as passivators causing a sudden passivation of Fe during a mass-transport controlled process across a salt film. Current oscillations appear over a wide potential region. The oscillation period as well as the induction period of time occurring before the onset of oscillation, both decrease by increasing the nitrate concentration. The effect of nitrates at lower and higher potentials is discussed in terms of the electrochemical and redox reactions of nitrate ions.