Potent,Metabolically Stable 2‐Alkyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐adenines as Adenosine A2A Receptor Ligands

Inhibition of adenosine A_2A receptors has been shown to elicit a therapeutic response in preclinical animal models of Parkinson’s disease (PD). We previously identified the triazolo‐9H‐purine, ST1535, as a potent A_2AR antagonist. Studies revealed that ST1535 is extensively hydroxylated at the ω‐1 position of the butyl side chain. Here, we describe the synthesis and evaluation of derivatives in which the ω‐1 position has been substituted (F, Me, OH) in order to block metabolism. The stability of the compounds was evaluated in human liver microsomes (HLM), and the affinity for A_2AR was determined. Two compounds, (2‐(3,3‐dimethylbutyl)‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐6‐amine ( 3 b ) and 4‐(6‐amino‐9‐methyl‐8‐(2H‐1,2,3‐triazol‐2‐yl)‐9H‐purin‐2‐yl)‐2‐methylbutan‐2‐ol ( 3 c ), exhibited good affinity against A_2AR (K_i=0.4 nM and 2 nM , respectively) and high in vitro metabolic stability (89.5 % and 95.3 % recovery, respectively, after incubation with HLM for two hours).     

Signalling chains with probe and adjust learning

Many models explain the evolution of signalling in repeated stage games on social networks, differently in this study each signalling game evolves a communication strategy to transmit information across the network. Specifically, I formalise signalling chain games as a generalisation of Lewis' signalling games, where a number of players are placed on a chain network and play a signalling game in which they have to propagate information across the network. I show that probe and adjust learning allows the system to develop communication conventions, but it may temporarily perturb the system out of conventions. Through simulations, I evaluate how long the system takes to evolve a signalling convention and the amount of time it stays in it. This discussion presents a mechanism in which simple players can evolve signalling across a social network without necessarily understanding the entire system.     

Italian multicentre study on microbial environmental contamination in dental clinics: a pilot study

The dental practice is associated with a high risk of infections, both for patients and healthcare operators, and the environment may play an important role in the transmission of infectious diseases. A microbiological environmental investigation was carried out in six dental clinics as a pilot study for a larger multicentre study that will be performed by the Italian SItI (Society of Hygiene, Preventive Medicine and Public Health) working group "Hygiene in Dentistry". Microbial contamination of water, air and surfaces was assessed in each clinic during the five working days of the week, before and during treatments. Air and surfaces were also examined at the end of the daily activity. A wide variation was found in microbial environmental contamination, both within the participating clinics and relative to the different sampling times. Microbial water contamination in Dental Unit Water Systems (DUWS) reached values of up to 26 × 10⁴ cfu/mL (colony forming units per millilitre). P. aeruginosa was found in 33% of the sampled DUWS and Legionella spp. in 50%. A significant decrease in the Total Viable Count (TVC) was recorded during the activity. Microbial air contamination showed the highest levels during dental treatments and tended to decrease at the end of the working activity (p < 0.05). Microbial buildup on surfaces increased significantly during the working hours. As these findings point out, research on microbial environmental contamination and the related risk factors in dental clinics should be expanded and should also be based on larger collections of data, in order to provide the essential knowledge aimed at targeted preventive interventions.     

A new sawing machine by diamond wire

Diamond wire is widely used for stone cutting; it is typically employed to extract a block in quarry and to square the block in a machining company. In particular, the frames to square or to cut the blocks present many technological limits, such as the high costs of the diamond wire, the frequent break of the diamond wire during cutting, the poor quality of cut surfaces, and the dangerous process and productivity lower than that of the same tool used in a quarry. The present work shows an innovative prototype machine to cut by a diamond wire which overcomes the aforementioned technological limits. The developed machine has a bridge frame among which two pulleys move the diamond wire as regards the stone block according with the feed speed. The diamond wire moves on the two pulleys with a cutting speed. A tensile force is applied to the wire that twists it during the contact with the stone, instead of keeping it along a straight direction parallel to the foundation of the machine. The twisting of the diamond wire makes the use of the wire itself more productive and safer, since the wear of each single bead during cutting is more uniform. Moreover, the resulting specific pressure acts on each bead along the arc of contact with the cut block and increases along the cutting direction from the entrance to the exit of the contact with the stone. The increasing of the specific pressure causes a bending of the diamond wire during the contact with the stone. The developed prototype was provided with a sensory system to measure both the cutting power and the tensile force of the diamond wire during experimental tests. In this way it was possible to verify the functionality of the prototype plant and, in the same time, to evaluate the productivity of the implemented cutting process.     

Exposure to fine and ultrafine particles from secondhand smoke in public places before and after the smoking ban, Italy 2005

Background

A smoking ban in all indoor public places was enforced in Italy on 10 January 2005.

Methods

We compared indoor air quality before and after the smoking ban by monitoring the indoor concentrations of fine (<2.5 μm diameter, PM_2.5) and ultrafine particulate matter (<0.1 μm diameter, UFP). PM_2.5 and ultrafine particles were measured in 40 public places (14 bars, six fast food restaurants, eight restaurants, six game rooms, six pubs) in Rome, before and after the introduction of the law banning smoking (after 3 and 12 months). Measurements were taken using real time particle monitors (DustTRAK Mod. 8520 TSI; Ultra‐fine Particles Counter‐TRAK Model 8525 TSI). The PM_2.5 data were scaled using a correction equation derived from a comparison with the reference method (gravimetric measurement). The study was completed by measuring urinary cotinine, and pre‐law and post‐law enforcement among non‐smoking employees at these establishments

Results

In the post‐law period, PM_2.5 decreased significantly from a mean concentration of 119.3 μg/m³ to 38.2 μg/m³ after 3 months (p<0.005), and then to 43.3 μg/m³ a year later (p<0.01). The UFP concentrations also decreased significantly from 76 956 particles/cm³ to 38 079 particles/cm³ (p<0.0001) and then to 51 692 particles/cm³ (p<0.01). Similarly, the concentration of urinary cotinine among non‐smoking workers decreased from 17.8 ng/ml to 5.5 ng/ml (p<0.0001) and then to 3.7 ng/ml (p<0.0001).

Conclusion

The application of the smoking ban led to a considerable reduction in the exposure to indoor fine and ultrafine particles in hospitality venues, confirmed by a contemporaneous reduction of urinary cotinine.     

Analysis of the gate current as a suitable indicator for FET degradation under nonlinear dynamic regime

Electron device degradation, although not directly accounted for, represents a key issue in microwave circuit design. This is especially true when the particular applications involved (e.g., satellite, military, consumer) do not allow or strongly discourage any kind of maintenance. As a matter of fact, in order to account for device degradation in circuit design, a suitable electron device model is needed which is able to predict the performance degradation as a function of the actual electrical regime involved in the device operation. Such a kind of model is not available in literature. In this paper, quantitative results are provided for device degradation indicators which correlate DC and RF stress experiments. These results can be considered an important step toward the definition of a nonlinear model accounting for device degradation.     

Searching for the center: Spatial cognition in the domestic chick (Gallus gallus).

Chicks learned to find food hidden under sawdust by ground-scratching in the central position of the floor of a closed arena. When tested in an arena of identical shape but a larger area, chicks searched at 2 different locations, one corresponding to the correct distance (i.e., center) in the smaller (training) arena and the other to the actual center of the test arena. When tested in an arena of the same shape but a smaller area, chicks searched in the center of it. These results suggest that chicks are able to encode information on the absolute and relative distance of the food from the walls of the arena. After training in the presence of a landmark located at the center of the arena, animals searched at the center even after the removal of the landmark. Marked changes in the height of the walls of the arena produced some displacement in searching behavior, suggesting that chicks used the angular size of the walls to estimate distances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fluidized state gelation of ceramic microspheres: Feasibility study of a continuous process and analysis of the chemical dehydration phenomena

A continuous gelation process for producing aluminum and zirconium hydroxide microparticles was conceived and tested in a lab‐scale apparatus. Fluidized state was devised as an appropriate hydrodynamic configuration to maintain the reacting sol microdrops suspended: stable non‐coalescing spherical gel particles in a size range quite below 100 μm were produced via gelation. The microspheres produced by a subsequent calcination step showed a diameter ranging between 2 μm and 20 μm. This powder, without further size classification, was an optimal product to manufacture test specimens by sintering. Measurements on the mechanical properties, such as toughness, flexural strength and hardness, classified the test bars as a very promising ceramic material. In order to enlighten the chemical drying phenomenon and devise the main governing mechanisms acting in the gelation reaction, an extremely simplified experimental system was set. A single drop of sol was deposited into a given amount of the dehydrating liquid medium and observed by an optical microscope; image analysis permitted us to identify the gel formation, the size reduction kinetics, as well as secondary phenomena.     

Reliability of RF MEMS switches due to charging effects and their circuital modelling

The reliability of RF MEMS switches is typically reduced by charging effects occurring in the dielectrics. The aim of this paper is to discuss these effects, and to propose analytical and equivalent circuit models which account for most of the physical contributions present in the structure.