Diastereoselective solution and multipin-based combinatorial array synthesis of a novel class of potent phosphinic metalloprotease inhibitors

The solution-phase synthesis and resolution of new phosphinopeptidic building blocks containing a triple bond was realized in high yields and optical purities (units 3 a-d). The absolute configuration of the target compounds was unambiguously established by NMR studies. A post-assembly diversification strategy of these blocks was developed through 1,3-dipolar cycloaddition of a variety of in situ prepared nitrile oxides. This strategy led to the rapid and efficient diastereoselective preparation of a novel class of isoxazole-containing phosphinic peptides (peptides 5 a-i). Solid-phase version of this strategy was efficiently achieved on multipin solid technology, by developing a new protocol for the coupling of P-unprotected dipeptidic blocks with solid supported amino acids in a quantitative and diastereoselective manner. Optimization of dipolar cycloadditions onto pin-embodied phosphinic peptides allowed the convenient preparation of this new class of pseudopeptides. The crude phosphinic peptides (9 a-k) were obtained in high yields and purity as determined by RP-HPLC. Inhibition assays of some of these peptides revealed that they behave as very potent inhibitors of MMPs, outmatching previously reported phosphinic peptides, in terms of potency (K(i) in the range of few nM).     

Dynamic thermoelastic effects for half-planes and half-spaces with nearly-planar surfaces

The effects of non-planarity on the dynamic surface temperature changes induced for plane-strain and 3D problems on the nearly-planar surfaces of, respectively, coupled thermoelastic half-planes and half-spaces by surface heat fluxes are treated. The nearly-planar nature of the surfaces allows the problem solutions to be written, following a standard perturbation scheme, as series expansions in a dimensionless surface contour amplitude parameter. The first, or zero-order, terms represent the ideal (planar) surface solutions, while the second, or first-order, terms represent corrections for non-planarity.Because the characteristic thermoelastic time is of O(10^–7)s, large-time asymptotic forms of the exact integral transform solutions can be used. These can be inverted exactly and used in Green's function operations to yield analytic, or integrals of analytic, expressions. Two types of thermal loading for the half-plane and yet a third type of thermal loading for the half-space are considered. Comparison of the zero- and first-order surface temperature changes for each case indicate that non-planarity gives rise for large times to changes in surface regions beyond those predicted by an ideal surface analysis. Moreover, the magnitudes of these changes can be more significant than the ideal surface results.     

Indoor measurements of microclimate variables and ozone in the church of San Vincenzo (Monastery of Bassano Romano — Italy): A pilot study

This experiment describes a way of operation in MMA-CH, Microclimate Multivariate Analysis for Cultural Heritage. It is realised by choosing appropriate meteorological and air composition parameters according to the environment to be investigated, measuring them by appropriate instruments and making acquisition of time series to find out all possible correlations. It is possible to understand how this branch of multivariate analysis could contribute to the “science of conservation” by applying an appropriate microclimatic and air composition monitoring and processing. Microclimate parameters such us air temperature, relative humidity, mixing ratio and air composition parameters such as tropospheric ozone content were monitored during a summer period to assess their impact on the cultural heritage of the Benedictine Monastery dedicated to San Vincenzo Martire (Diocletian's Christians persecution). This marvellous place is settled next to Bassano Romano village, in the Sabatini mountains rural area. The importance of the site is established by the presence of many art treasures, like 2 frescos of '700, 2 frescos of '600 (Caravaggio School) and by a marble statue of Jesus (“The Jesus cross carrying”) which is recently attributed to Michelangelo as the original one.     

An analytical model for the determination of the cup-burner minimum extinguishing concentration of inert fire suppression agents

An analytical model based on the perfectly stirred reactor (PSR) concept is developed and utilized in the prediction of the minimum extinguishing concentration (MEC) of inert fire suppression agents that is established in the standard cup-burner test. In the PSR-based approach, both thermal (heat absorption) and chemical mechanisms of fire suppression can be captured. The assumed perfect mixing, on the other hand, prevents the ability to capture transport related mechanisms. In past work, the PSR approach using detailed chemistry was demonstrated to be effective in reproducing the MEC albeit with the need of single point calibration. The closed form solution presented herein becomes possible when the detailed chemistry is simplified to a single step, mole preserving chemical reaction. At the core of the model is an analytical expression for the extinction temperature which is transcendental and thus requires a numerical iterative solution. The analytical model is first verified using a traditional computational PSR (CHEMKIN package) that employs the same reduced kinetics as the analytical model. Subsequently, results from the analytical model are contrasted to those from a traditional PSR with detailed chemistry, from a semi-analytical approach that assumes heat absorption by the agent is the primary extinguishing mechanism, and from experimental data of various research groups. Good agreement is achieved validating the analytical model as a simple and accurate approach to determine the MEC. The analytical model is also used in a parametric assessment of the impact of geographic altitude (i.e. effect of ambient pressure) on the MEC and results are in good agreement with those of a traditional PSR with detailed chemistry.     

Velocity measurements of flow through a step stenosis using Magnetic Resonance Imaging

 Magnetic resonance imaging (MRI) is a versatile noninvasive tool for achieving full-field quantitative visualization of complex fluid flows. The MRI signal results from the interaction of radio-frequency (RF) pulses with nuclear spins exposed to a strong static magnetic field. The two main techniques of MRI velocimetry are time-of-flight and phase contrast techniques. Time-of- flight techniques involve tagging and tracking a material volume of fluid, whereas phase contrast techniques use magnetic field gradients to encode velocity information into the phase of the MRI signal. In this study, both techniques are used to probe the pressure-driven steady flow of water in a pipe with a step stenosis. The velocity measurements were then compared with computational results obtained using the FIDAP software package. The experiments show that the phase contrast method gives more accurate results, with 90% of the measurements within 10% of the local computational fluid dynamics (CFD) velocity predictions at Re = 100 and 94% of the measurements within 10% of the local CFD predictions at Re = 258. Although the time-of-flight experiments were not as accurate, they provide a good qualitative image of the flow field. Sources of the discrepancies between the MRI data and the CFD results are also discussed, including acceleration and spin flow-through artifacts. Received: 7 April 1999/Accepted: 20 December 1999     

Chitin Isolation and Chitosan Production from House Crickets (Acheta domesticus) by Environmentally Friendly Methods

Alternative methods were evaluated for chitin isolation from Acheta domesticus. Chemical demineralization was compared to fermentation with Lactococcus lactis, citric acid treatment, and microwave treatment, leading to a degree of demineralization of 91.1 ± 0.3, 97.3 ± 0.8, 70.5 ± 3.5, and 85.8 ± 1.3%, respectively. Fermentation with Bacillus subtilis, a deep eutectic solvent, and enzymatic digestion were tested for chitin isolation, generating materials with less than half the chitin content when compared to alkaline deproteinization. Chitosan was produced on a large scale by deacetylation of the chitinous material obtained from two selected processes: the chemical treatment and an alternative process combining L. lactis fermentation with bromelain deproteinization. The chemical and alternative processes resulted in similar chitosan content (81.9 and 88.0%), antioxidant activity (59 and 49%), and degree of deacetylation (66.6 and 62.9%), respectively. The chitosan products had comparable physical properties. Therefore, the alternative process is appropriate to replace the chemical process of chitin isolation for industrial applications.