Structure-based drug design to the discovery of new 2-aminothiazole CDK2 inhibitors

N-(5-Bromo-1,3-thiazol-2-yl)butanamide (compound 1) was found active (IC50=808 nM) in a high throughput screening (HTS) for CDK2 inhibitors. By exploiting crystal structures of several complexes between CDK2 and inhibitors and applying structure-based drug design (SBDD), we rapidly discovered a very potent and selective CDK2 inhibitor 4-[(5-isopropyl-1,3-thiazol-2-yl)amino] benzenesulfonamide (compound 4, IC50=20 nM). The syntheses, structure-based analog design, kinases inhibition data and X-ray crystallographic structures of CDK2/inhibitor complexes are reported.     

Virtual reality as a communication process

In this work, we consider immersive Virtual Reality (VR) as a communication process between humans, mediated by computer systems, which uses interaction, visualization, and other sensory stimuli to convey information. From this viewpoint, it is relevant to understand how VR can solve a given communication problem, what is therefore the expressive power of VR system, i.e., its ability in establishing the communication, what are the guidelines to design an effective system, and what are the more relevant models of VR applications. Firstly, we try to clarify the notion of reality in Virtual Reality systems and conclude that reality is not an intrinsic characteristic of VR, rather the result of a conventional way of coding information. The purpose of coding is to lead the observer to the conclusion that the VR set is what is called in italian as verisimile (from Latin veri similis), i.e., ??similar-to-the-real-thing??. So the creation of an effective VR application is an artifice or an illusion. But in order to avoid an over-reliance on the creativity of the VR designer, we intend to identify a solid ground on which different kinds of VR solutions can be considered in terms of their ability to solve the desired communication objective. To this aim, we will rely on methods derived from rhetoric to semiotics.     

Analysis of power saving and its impact on web traffic in cellular networks with continuous connectivity

In this work, we analyze the power saving and its impact on web traffic performance when customers adopt the continuous connectivity paradigm. To this end, we provide a model for packet transmission and cost. We model each mobile user’s traffic with a realistic web traffic profile, and study the aggregate behavior of the users attached to a base station by means of a processor-shared queueing system. In particular, we evaluate user access delay, download time and expected economy of energy in the cell. Our study shows that dramatic energy saving can be achieved by mobile devices and base stations, e.g., as much as 70%–90% of the energy cost in cells with realistic traffic load and the considered parameter settings.     

4-Sulfamoylphenylalkylamides as Inhibitors of Carbonic Anhydrases Expressed in Vibrio cholerae

A current issue of antimicrobial therapy is the resistance to treatment with worldwide consequences. Thus, the identification of innovative targets is an intriguing challenge in the drug and development process aimed at newer antimicrobial agents. The state-of-art of anticholera therapy might comprise the reduction of the expression of cholera toxin, which could be reached through the inhibition of carbonic anhydrases expressed in Vibrio cholerae (VchCAα, VchCAβ, and VchCAγ). Therefore, we focused our interest on the exploitation of sulfonamides as VchCA inhibitors. We planned to design and synthesize new benzenesulfonamides based on our knowledge of the VchCA catalytic site. The synthesized compounds were tested thus collecting useful SAR information. From our investigation, we identified new potent VchCA inhibitors, some of them displayed high affinity toward VchCAγ class, for which few inhibitors are currently reported in literature. The best interesting VchCAγ inhibitor (S)-N-(1-oxo-1-((4-sulfamoylbenzyl)amino)propan-2-yl)furan-2-carboxamide ( 40 ) resulted more active and selective inhibitor when compared with acetazolamide (AAZ) as well as previously reported VchCA inhibitors.     

Switched nonlinear systems with state-dependent dwell-time

The asymptotic convergence of a switched nonlinear system in the presence of disturbances is studied. The system switches among a family of integral input-to-state stable systems. The time between two consecutive switchings is not less than a value τ_D. This dwell-time τ_D is allowed to take different values according to a function whose argument is the state of the system at the switching times. We propose a dwell-time function which depends on the comparison functions which characterize the integral input-to-state stability property and guarantees the state of the switched system to converge to zero under the action of disturbances with “bounded energy”. The main feature of the analysis is that it does not rely on the property for the switching to stop in finite time. The two important cases of locally exponentially stable and feedforward systems are analyzed in detail.     

Multigram-scale production of aliphatic carboxylic acids by oxidation of alcohols with Acetobacter pasteurianus NCIMB 11664

Acetobacter pasteurianus NCIMB 11664 was selected for multigram-scale production of different aliphatic carboxylic acids through oxidation of the corresponding alcohols after screening different acetic acid bacteria. Continuous production was carried out using an air-lift reactor, with overall yields of 1-propionic, 1-butyric, 2-methyl-1-butyric and 3-methyl-1-butyric acids ranging from 45 to 61 g dm⁻³. ©1997 SCI     

Near-visible stereolithography of a low shrinkage cationic/free-radical photopolymer blend and its nanocomposite

In this work, a newly prepared cationic/free-radical photopolymer, which consists of two epoxies and a tetrafunctional acrylate, is presented for the first time for a visible light stereolithography (SL), showing the advantages of both cationic and free-radical resins. An onium salt, commonly used as a cationic UV initiator, and a photosensitizer make the blend suitable for a near-visible (405 nm) SL. An increase in the polymerization rate and a drop in the induction period are observed for the newly prepared cationic/free-radical blend, compared with either only cationic systems or free-radical resins. This suggests that the combination of cationic and free-radical polymerizations in a single resin has a positive synergistic effect. The addition of silica nanoparticles to the blend provides a reinforcing and toughening effect. Indeed, the resin loaded with silica shows a 31% increase in the elastic modulus, compared with the unfilled resin. Regarding the values of tensile strength and elongation at break, they, respectively, grow by 47 and 15%, when the nanocomposite resin is compared with the neat resin. A very low volumetric shrinkage of 0.7% and a remarkable printing quality of objects obtained with this new photopolymer will enable the 3D printing of microrobots, bioengineering microdevices, and sensors. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48333.     

A Customizable Instrument for Measuring the Mechanical Properties of Thin Biomedical Membranes

Summary: A customized instrument has been developed as part of multidisciplinary research work relating to the development of a biodegradable vascular scaffold. This instrument aims to measure the mechanical properties of elastic and viscoelastic thin membranes with tissue engineering applications. Uniform and omni‐directional pressure is applied on the whole membrane which is uniformly clamped and submerged into a liquid medium. The mechanical testing described in this study is focused on the stress‐strain curves of polycaprolactone (PCL) films after different treatments. The influence of Dulbecco's modified Eagle's culture medium, L929 fibroblast culture, NaOH treatment and film thickness on the mechanical properties of PCL films was evaluated after different times. These studies show that the PCL degradation process is influenced by immersion in the culture medium, inducing an increment in the slope of the pressure‐dilation curve which is indicative of an increase in the polymer stiffness. On the other hand, long NaOH treatments make PCL films have more flexible behavior.

A computerized version of the instrument: (1) Electrical compressor; (2) Filter; (3) Voltage‐pressure converter; (5) Pressure sensor; (6) Differential pressure sensor; (7–8) Main and auxiliary pipettes; (9) Printed circuit board; (10) Personal computer.