The dimerization domain of LFB1/HNF1 related transcription factors: a hidden four helix bundle?

LFB1/HNF1 and LFB3/HNF1ß bind DNA as dimers and formheterodimers together in vivo and in vitro. The dimerizationdomain has been located in both proteins in the 32 N-terminalresidues. In previous papers we have described the conformationalstability as determined by CD and the secondary structure byNMR studies of a peptide with the amino acid sequence of thedimerization domain of LFB1/ HNF1. This study presents a morecomplete characterization of similar synthetic peptides spanningthe LFB3/HNF1ß dimerization domain and the /ßheterodimer. The HNF1 peptides represent an example of structureswhich cannot be determined by NOE data alone because they arenot sufficient to define one unique solution. An approach ispresented which combines NMR data, the protein structure databaseand structural analyses according to known principles of proteinstructure. On this basis we are able to determine possible solutionsand to identify a four helix bundle as the structure most consistentwith the experimental evidence.     

Structure-activity relationship study of 16 a-thiocamptothecins: an integrated in vitro and in silico approach

The instability of the hydroxylactone E ring represents a critical drawback of camptothecins, because the lactone ring is recognized to be essential for stabilization of topoisomerase I‐mediated DNA cleavage. In an attempt to investigate the effect of the thiopyridone pharmacophofore on the molecular and pharmacological features of the drug, we prepared a series of novel 16 a‐thiocamptothecin analogues. Due to the sulfur atom, a destabilization of the hydrogen bond between the hydroxy group in position 17 of the opened E ring and the carbonyl of the pyridone moiety is predicted, thus shifting the equilibrium toward the closed lactone form and increasing the lipophilic properties of the compounds. This feature was associated with superior antiproliferative potency, with reduced interaction with the human serum albumin and with substantial increase of the persistence of the topoisomerase I–DNA cleavable complex. These effects were prominent for thio‐SN38, the most active compound of the series. The favorable interactions at the molecular and cellular level of the reported thiocamptothecins confer promising features, and these compounds warrant preclinical development.     

Oxidation of 3,4-dihydroxybenzoic acid by means of hydrogen peroxide in aqueous goethite slurry

The oxidation by H2O2 of 3,4-dihydroxybenzoic acid (3,4-DHB) in aqueous/goethite slurry at varying operating conditions (catalyst load, temperature, pH, substrate and hydrogen peroxide starting concentration) is investigated. At adopted catalyst loads the observed kinetic developments are consistent with a non-radicalic oxidation mechanism involving the interaction between hydrogen peroxide and 3,4-DHB acid both adsorbed on the active sites of the catalyst. The temperature dependence of rate parameters for the proposed model is also assessed.     

Sustainability of steel structures: towards an integrated approach to life-time engineering design

Nowadays, the construction sector is more and more oriented toward the promotion of sustainability in all its activities. The goal to achieve is the optimization of performances, over the whole life-cycle, with respect to environmental, economic and social requirements. According to the latest advances, the concept of sustainability applied to constructions covers a number of branches such as life-cycle costing, ecology, durability and even structural design. Several procedures and design tools have been implemented in the framework of international research. Indeed the current trend in civil engineering research is moving towards life-time engineering, with the aim to implement integrated methodologies to consider as a whole all the sustainability requirements according to time-dependent multi-performance-based design approaches. Following a general introduction of the concept of sustainability applied to constructions, this paper presents an overview of life-time engineering methodologies according to the current state-of-the-art. In particular the methods currently received by International Standards are discussed. A special focus is devoted to the durability design of metal structures with respect to the degradation phenomena able to impair the structural capacity over time. Finally a proposal towards an integrated approach to life-time engineering design of steel structures and needs for further advances are presented.     

Kinematics of a new spherical parallel manipulator with three equal legs: The 3‐URC wrist

Parallel manipulators are constituted of two rigid bodies, one movable (platform) and the other fixed (base), connected by a number of kinematic chains (legs). Manipulators with all equal legs that have the actuators adjacent to the base allow the use of simplified design procedures and manufacturing processes. Moreover, they are able to reach high performances. Further manufacturing simplifications can be obtained if only revolute pairs and passive cylindrical pairs are used. This article presents a new spherical parallel manipulator, named the 3‐URC wrist. The 3‐URC wrist is not overconstrained. It has three equal legs having only passive cylindrical pairs and revolute pairs with the actuators adjacent to the base. The 3‐URC wrist mounting and manufacturing conditions making spherical motions of the platform possible are defined. Then the position analysis and the mobility analysis of the 3‐URC wrist are solved. Finally, the singularity conditions are written in explicit form and geometrically interpreted. © 2001 John Wiley & Sons, Inc.     

Measurement of intrinsic properties of amyloid fibrils by the peak force QNM method

We report the investigation of the mechanical properties of different types of amyloid fibrils by the peak force quantitative nanomechanical (PF-QNM) technique. We demonstrate that this technique correctly measures the Young's modulus independent of the polymorphic state and the cross-sectional structural details of the fibrils, and we show that values for amyloid fibrils assembled from heptapeptides, α-synuclein, Aβ(1-42), insulin, β-lactoglobulin, lysozyme, ovalbumin, Tau protein and bovine serum albumin all fall in the range of 2-4 GPa.     

Intercomparison campaign of spectroradiometers for a correct estimation of solar spectral irradiance: results and potential impact on photovoltaic devices calibration

This paper describes the results of an intercomparison of spectroradiometers for global and direct normal incidence irradiance in the visible and near‐infrared spectral regions together with an assessment of the impact these results may have on the estimation of the short‐circuit current (I_SC) calibration of photovoltaic devices and on the spectral mismatch calculation. The intercomparison was conducted in the framework of the European project Apollon with the additional participation of external partners from the Italian project for the long‐term monitoring of solar radiation for photovoltaics. Six institutions and six spectroradiometer systems, representing different technologies and manufacturers, were involved. Prior to the intercomparison, all participating partners calibrated their own instrument(s) according to their usual procedures in order to verify the entire measuring and traceability chain. The difference in measured spectra shape and amplitude showed to have an impact on I_SC calculation of less than 3% and less than 6% for single‐junction and multi‐junction devices, respectively. When only the shape of the spectra is considered, the spectral mismatch ranges from 1.7% to 4.7% depending on the spectral response of the device. Copyright © 2013 John Wiley & Sons, Ltd.