Pathogenic Mutations Shift the Equilibria of α‐Synuclein Single Molecules towards Structured Conformers

α‐synuclein (α‐Syn) is an abundant brain protein whose mutations have been linked to early‐onset Parkinson's disease (PD). We recently demonstrated, by means of a single‐molecule force spectroscopy (SMFS) methodology, that the conformational equilibrium of monomeric wild‐type (WT) α‐Syn shifts toward β‐containing structures in several unrelated conditions linked to PD pathogenicity. Herein, we follow the same methodology previously employed for WT α‐Syn to characterize the conformational heterogeneity of pathological α‐Syn mutants A30P, A53T, and E46K. Contrary to the bulk ensemble‐averaged spectroscopies so far employed to this end by different authors, our single‐molecule methodology monitored marked differences in the conformational behaviors of the mutants with respect to the WT sequence. We found that all the mutants have a much higher propensity than the WT to adopt a monomeric compact conformation that is compatible with the acquiring of β structure. Mutants A30P and A53T show a similar conformational equilibrium that is significantly different from that of E46K. Another class of conformations, stabilized by mechanically weak interactions (MWI), shows a higher variety in the mutants than in the WT protein. In the A30P mutant these interactions are relatively stronger, and therefore the corresponding conformations are possibly more structured. The more structured and globular conformations of the mutants can explain their higher propensity to aggregate with respect to the WT.     

Characterization and imaging of SAW grooved transducer acousticfield by SLAM

Quantitative characterization of the surface acoustic field radiated forward, backward, and in orthogonal directions by the grooved transducer, implemented onto a glass substrate, is accomplished by a scanning laser acoustic microscope (SLAM) operating at 31 MHz. The surface acoustic wave (SAW) amplitude is measured as a function of the number of grooves and the position of the bulk acoustic wave (BAW) transducer. The number of the operating grooves efficiently contributing to the SAW response is estimated. Remarkable reflection of the SAW beam between two identical gratings is observed     

Hepatic and Extrahepatic Sources and Manifestations in Endoplasmic Reticulum Storage Diseases

Alpha-1-antitrypsin (AAT) and fibrinogen are secretory acute phase reactant proteins. Circulating AAT and fibrinogen are synthesized exclusively in the liver. Mutations in the encoding genes result in conformational abnormalities of the two molecules that aggregate within the rough endoplasmic reticulum (RER) instead of being regularly exported. That results in AAT-deficiency (AATD) and in hereditary hypofibrinogenemia with hepatic storage (HHHS). The association of plasma deficiency and liver storage identifies a new group of pathologies: endoplasmic reticulum storage disease (ERSD).     

Polarity reversal induced by electrochemically generated thiazol-2-ylidenes: The Stetter reaction

The inversion of the normal reactivity (umpolung) of aldehydes has been induced via N-heterocyclic carbenes (NHCs) thiazol-2-ylidenes 2a or 3a, generated by simple electrolyses of solutions containing thiazolium salt 2 or 3. Accordingly, 1,4-dicarbonyl compounds have been obtained, in mild conditions and in moderate to very high yields, via 1,4-addition of the Breslow intermediates to the suitable Michael acceptor. The procedure has been performed in classical organic solvents (VOCs) as well as in room temperature ionic liquids (RTILs). The different reactivity of aliphatic aldehydes vs the one of aromatic and heteroaromatic aldehydes has been emphasized.     

New Blended Cement from Polishing and Glazing Ceramic Sludge

Waste generated in ceramic tiles manufacturing is not usually recycled inside the productive plant, but rather disposed to landfill. This paper deals with ceramic residues from polishing and glazing processes, as constituents for innovative blended cements. New binders made up of 75% CEM I 52.5 R and 25% residues were chemically, physically, and mechanically characterized with reference to EN 197-1 requirements and the results compared with ordinary Portland cement. Mechanical strength development and microstructure of the relevant mortar have been investigated up to 90 days of curing, and the behavior of polishing and glazing residues as cement constituents is reported.     

Analysis and design of digital predictive controller for PFC Cuk converter

A digital predictive control strategy for Power Factor Correction (PFC) is presented in this paper. The duty cycles required to achieve unity power factor in one half line period are calculated in advance by using a predictive algorithm and implemented using low cost PIC Microcontroller. A single stage PFC circuit controlled by these pre-calculated duty cycles can achieve sinusoidal current waveform. The output voltage of PFC circuit is regulated by an outer PI controller. A low frequency, small signal model of the rectifier is developed in order to design a PI voltage controller. A prototype of front end AC–DC converter followed by DC–DC Cuk converter controlled by a PIC Microcontroller is developed. Both the simulation and experimental results reveal that the proposed digital predictive strategy provides low THD, high power factor and better performance due to its lower calculation requirement and simple implementation.     

Electrogenerated N-heterocyclic carbene: N-acylation of chiral oxazolidin-2-ones in ionic liquids

An electrochemical procedure for the N-acylation of chiral oxazolidin-2-ones, in the absence of volatile molecular organic solvents, has been set up via electrolyses of ionic liquid [bmim]BF₄ containing oxazolidin-2-ones followed by addition of saturated or unsaturated anhydrides. N-acyloxazolidin-2-ones were isolated in good to elevated yields. The electrochemically induced N-acylation of chiral oxazolidin-2-ones occurs with total retention of the absolute configuration of all the chiral atoms. The electrogenerated carbene (1-butyl-3-methyl-1H-imidazol-2-ylidene) has been indicated as the base involved in the deprotonation of chiral oxazolidin-2-ones.     

ESD sensitivity of a GaAs MMIC microwave power amplifier

The EOS/ESD sensitivity of the main circuit blocks of a complete GaAs multi-stage power amplifier for microwave applications was investigated under HBM, MM and TLP regimes. Hard breakdown failure modes were identified due to passive components failure. The high current injection state of active components was also analyzed.     

Localization of the human phosphotyrosine phosphatase-related genes (h-PRL-1) to chromosome bands 1p35-p34, 17q12-q21, 11q24-q25 and 12q24

The h-PRL-1 gene codes for a new phosphotyrosine phosphatase that may play an important role in the control of basic cellular processes such as cell growth and proliferation. Using the cDNA of the h-PRL-1 gene as a probe, we examined a somatic mouse and hamster x human hybrid panel and found that chromosomes 1, 17 and 11 harbor sequences homologous to h-PRL-1. By in situ hybridization of metaphase spreads, subchromosomal localizations were determined at bands 1p35-p34, 17q12-q21 and 11q24-q25; in addition, a faint signal was detected at 12q24. The chromosomal assignment of the genes homologous to h-PRL-1 will help the investigation of its possible involvement in human diseases involving genetic alteration at these chromosomal regions.     

B-ISDN economical evaluation in metropolitan areas

The economical estimation of B-ISDN development in metropolitan areas, with particular reference to the application of the asynchronous transfer mode (ATM) techniques is addressed. The results achieved by applying models and methods developed in the framework of RACE 1044-EPF Case Study E (Evolution Prospects for Metropolitan Public Networks) to an urban area of 2 million inhabitants. Equipment volumes are estimated as a function of different demand scenarios, equipment evolution, and network performances. Economical figures that verify the cost-effectiveness of alternative developments and the viability of alternative introduction policies of B-ISDN are derived. The economical impact of fulfilling service integrity requirements of specific demand segments is evaluated. Usable planning guidelines and evolutionary strategies as regards network architecture, system introduction, and growth policies are defined