Small‐Molecule Inhibitors of AF6 PDZ‐Mediated Protein–Protein Interactions

PDZ (PSD‐95, Dlg, ZO‐1) domains are ubiquitous interaction modules that are involved in many cellular signal transduction pathways. Interference with PDZ‐mediated protein–protein interactions has important implications in disease‐related signaling processes. For this reason, PDZ domains have gained attention as potential targets for inhibitor design and, in the long run, drug development. Herein we report the development of small molecules to probe the function of the PDZ domain from human AF6 (ALL1‐fused gene from chromosome 6), which is an essential component of cell–cell junctions. These compounds bind to AF6 PDZ with substantially higher affinity than the peptide (Ile‐Gln‐Ser‐Val‐Glu‐Val) derived from its natural ligand, EphB2. In intact cells, the compounds inhibit the AF6–Bcr interaction and interfere with epidermal growth factor (EGF)‐dependent signaling.     

Environmental Innovations,Local Networks and Internationalization

This paper investigates the forces correlated with environmental innovations (EIs) introduced by firms in local production systems (LPS). The role of inter-firm network relationships, agglomeration economies and internationalization strategies is jointly analysed for a sample of 555 firms in the Emilia–Romagna (ER) region (North-East Italy). Cooperating with a certain kind of local actors—i.e. suppliers and universities—is the most important EI driver for the investigated firms, along with their training coverage and their adoption of information and communication technologies. The role of agglomeration economies is instead less clear-cut. They spur EIs only in the presence of established LPS, with idiosyncratic sector specialization, while conversely they act as EI barriers. Networking effects and agglomeration economies are instead found to strongly promote the adoption of EIs by multinational firms, thus highlighting the importance of local–global interactions. Interesting specifications for these results are found for particular kinds of EIs, in such fields as CO₂ abatement and ISO labelling, generally extending the analysis of EI drivers by joining local and international factors. In addition, the role of regulatory sector factors confirms the induced innovation hypothesis and provides a robustness check to our results.     

Design of an integrated low-noise read-out system for DNA capacitive sensors

This paper presents an electronic system for a fast DNA label-less detection. The sensitivity of the capacitive sensor in use is improved by depositing an insulating self-assembled monolayer (SAM) over the golden electrodes. The capacitance shift due to the hybridization effect is monitored by means of a charge-sensitive amplifier and digitalized by means of a comparator and a counter. The read-out solution demonstrates the ability to identify a 0.01% variation on the capacitive value of the sensor. Results from measurements with the optimized sensor show the reliability of the electronics. The investigated solution is suitable for monolithic systems or for a micro-fabricated array of sensors. An example of the integrated front-end is described and performances and noise evaluation are reported here.     

Thermal analysis in coated cutting tools

This work studies the heat influence in cutting tools considering the variation of the coating thickness and the heat flux. K10 and diamond tools substrate with TiN and Al₂O₃ coatings were used. The numerical methodology utilizes the ANSYS^® CFX software. Boundary conditions and constant thermo physical properties of the solids involved in the numerical analysis are known. To validate the proposed methodology an experiment is used. The TiN and Al₂O₃ coatings did not show satisfying results during a continuous cutting process. It showed a slight reduction in the heat flux for the 10 (µm) TiN and Al₂O₃ coatings.     

Recursive partial realization for 2-D data arrays

In this paper an attempt is made to provide a proper formalization to the partial realization problem for discrete linear causal shift invariant 2-D systems. The approach falls into the class of 2-D Padé approximations; the results, however, are new, since the rational representation matches all the samples of a 2-D partial sequence. The realization algorithm, though characterized by a high complexity, exhibits a recursive structure and allows for a good computational economy.     

A systematic review on the functional testing of semantic web services

Semantic web services are gaining more attention as an important element of the emerging semantic web. Therefore, testing semantic web services is becoming a key concern as an essential quality assurance measure. The objective of this systematic literature review is to summarize the current state of the art of functional testing of semantic web services by providing answers to a set of research questions. The review follows a predefined procedure that involves automatically searching 5 well-known digital libraries. After applying the selection criteria to the results, a total of 34 studies were identified as relevant. Required information was extracted from the studies and summarized. Our systematic literature review identified some approaches available for deriving test cases from the specifications of semantic web services. However, many of the approaches are either not validated or the validation done lacks credibility. We believe that a substantial amount of work remains to be done to improve the current state of research in the area of testing semantic web services.     

Metabolites from the biodegradation of di-ester plasticizers by Rhodococcus rhodochrous

The plasticizers di-2-ethylhexyl phthalate (DEHP) and di-2-ethylhexyl adipate (DEHA) are ubiquitous in the environment and undergo partial biodegradation in the presence of soil micro-organisms. The validity of a proposed pathway for the degradation of these plasticizers by Rhodococcus rhodochrous has been confirmed by the identification of 2-ethylhexanal in gas phase emissions. Complete analyses of the aqueous and gas phases were able to account for more than 98% of the 2-ethylhexanol component of the DEHA added at the beginning of a growth study. Of this, 25% was either 2-ethylhexanol or 2-ethylhexanal that had been stripped into the gas phase and, at most, only 2% of the 2-ethylhexanol component could have been removed by mineralization. It is concluded that plasticizers are of significant environmental concern due to the resistance of the metabolites to biodegradation and their known health impacts. Two of the metabolites are of added concern due to their volatility and their potential impact on indoor air quality.     

Aramid pulp treated with imidazolium ionic liquids as a filler in rigid polyurethane bio-foams

This article reports an aramid pulp (AP) treated with two ionic liquids (IL), namely 1-n-butyl-3-methylimidazolium chloride (C₄.Cl) and 1-carboxymethyl-3-methylimidazolium chloride (HO₂C), and its use as a filler in reinforced rigid polyurethane foams (RPUF). The RPUF were incorporated with the treated AP at three weight fractions (c.a. 0.1, 0.5, and 1.0 wt%) and were produced by the free rising method. The results showed that the studied IL promoted a better interaction between the AP and the RPUF system, which increased the overall reactivity, imparting a higher cell anisotropy. This also yielded a positive effect in mechanical properties and thermal stability of the RPUF. Compared to the neat RPUF, outstanding increases of approximately 50 and 20% were achieved in compressive modulus and strength, respectively. In all, the use of IL promoted increased compatibility between matrix and reinforcement, especially that HO₂C IL.     

Removal of fulvic acid from aqueous media by adsorption onto modified vermiculite

Clay minerals are low cost materials that can be structurally modified and exploited for removal of natural organic matter from freshwaters. The present study shows that vermiculites modified by ion exchange with hexadecyltrimethylammonium or intercalation with poly(hydroxy iron) cations are potential adsorbents for removal of fulvic acid, whereas the adsorption on the raw clay mineral is negligible. The efficiency of the modified vermiculite was evaluated by measuring adsorption isotherms by the batch technique using initial fulvic acid concentrations between 2.5 and 50.0 mg L^− 1, with one hour of contact time. At least 94% of the fulvic acid initially present in a 20 mg L^− 1 solution was sorbed onto either the intercalated poly(hydroxy iron) cations or the organically modified vermiculite. Up to an initial concentration of 5.0 mg L^− 1 the adsorption is irreversible, and no quantifiable fulvic acid was measured in the desorption experiments. For initial fulvic acid concentrations between 10.0 and 50.0 mg L^− 1, desorption was between 2.3% and 4.9% for Fe(III) intercalated vermiculite, and between 1.4% and 9.2% for the organoclay. The adsorption percentages on intercalated poly(hydroxy iron) cations increased upon lowering pH and increasing the ionic strength, indicating the occurrence of strong binding mechanisms such as ligand exchange. Adsorption percentage of fulvic acid onto the organoclay also increased with lowering of pH, but in this case the adsorption percentages showed a small decrease at high ionic strength, suggesting that electrostatic attraction plays an important role in the adsorption process.