Novel Glass‐Ceramic Composition as Sealant for SOFCs

This work deals with the design, the characterization, and testing of a novel glass‐ceramic to be used as sealant for planar solid oxide fuel cells and its compatibility with Mn_1.5Co_1.5O₄‐coated Crofer22APU. Thermal, sintering, and crystallization behavior and thermo mechanical properties of the sealant are reviewed and discussed, indicating therefore that these compositions can be deposited at 850°C and provide an excellent compatibility with both the Mn_1.5Co_1.5O₄‐coated Crofer22APU and the anode‐supported electrolyte. In particular, Mn_1.5Co_1.5O₄‐coated Crofer22APU/sealant/anode‐supported‐electrolyte joined samples have been submitted to thermal tests (in air atmosphere) from RT to 800°C (SOFC operating temperature) up to 500 h. No interactions, cracks formation, or failure were observed at the Mn_1.5Co_1.5O₄‐coated Crofer22APU/sealant interface and between the glass‐ceramic and the anode‐supported‐electrolyte after 500 h of thermal tests in air atmosphere.     

Design and technical status of the EU contribution to ITER

Europe is involved in the procurement of most of the high-technology items for the ITER device (e.g. parts of the superconducting Toroidal (TF) and Poloidal Field (PF) coils, the vacuum vessel (VV), the in-vessel components, the remote handling, the additional heating systems, the tritium plant and cryoplant and finally parts of the diagnostics). In many cases the technologies required to manufacture these components are well established, in others there is still ongoing design and R&D work to select and optimise the final design solutions and to consolidate the underlying technologies as, for example, in the areas of heating and current drive, plasma diagnostics, shield blanket and first wall, remote handling, etc. A design review has recently been conducted by the ITER Organisation, with the support of the Domestic Agencies (DAs) established by the countries participating to ITER, to address the remaining outstanding technical issues and understand the associated implications for design, machine performance, schedule and cost.This paper provides an update of the design and technical status of EU contributions to ITER.     

A compact instrumentation amplifier for MEMS thermal sensor interfacing

A compact CMOS instrumentation amplifier, based on a properly modified second order G _m?CC low pass filter (LPF), is proposed as a possible readout channel for integrated thermal sensors. Low noise and low offset characteristics are obtained by applying chopper modulation to the input transconductor. The high input thermal noise density, typical of low frequency G _m?CC filters, has been significantly reduced by adopting a two-stage topology for the first transconductor. Using this approach, an input noise density adequate for thermal sensor interfacing was obtained with no need of off-chip capacitors. The intrinsic filtering property of the amplifier effectively rejects the modulated offset ripple, allowing direct connection of the amplifier output to a low sampling rate AD converter. An original switching strategy involving swapping of the input and feedback ports is used to improve the gain precision. The effectiveness of the technique is proven by means of analytical arguments and electrical simulations performed on a prototype, designed with the STMicroelectronics BCD6s process.     

Specific Cerebrospinal Fluid SerpinA1 Isoform Pattern in Alzheimer’s Disease

SerpinA1 (α1-antitrypsin) is a soluble glycoprotein, the cerebrospinal fluid (CSF) isoforms of which showed disease-specific changes in neurodegenerative disorders that are still unexplored in Alz-heimer’s disease (AD). By means of capillary isoelectric focusing immunoassay, we investigated six serpinA1 isoforms in CSF samples of controls (n = 29), AD-MCI (n = 29), AD-dem (n = 26) and Lewy body disease (LBD, n = 59) patients and correlated the findings with CSF AD core biomarkers (Aβ42/40 ratio, p-tau, t-tau). Four CSF serpinA1 isoforms were differently expressed in AD patients compared to controls and LBD patients, especially isoforms 2 and 4. AD-specific changes were found since the MCI stage and significantly correlated with decreased Aβ42/40 (p < 0.05) and in-creased p-tau and t-tau levels in CSF (p < 0.001). Analysis of serpinA1 isoform provided good di-agnostic accuracy in discriminating AD patients versus controls (AUC = 0.80) and versus LBD patients (AUC = 0.92), with best results in patients in the dementia stage (AUC = 0.97). SerpinA1 isoform expression is altered in AD patients, suggesting a common, albeit disease-specific, in-volvement of serpinA1 in most neurodegenerative disorders.     

Glycaemic Control in Patients Undergoing Percutaneous Coronary Intervention: What Is the Role for the Novel Antidiabetic Agents? A Comprehensive Review of Basic Science and Clinical Data

Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and revascularization through percutaneous coronary interventions (PCI) significantly improves survival. In this setting, poor glycaemic control, regardless of diabetes, has been associated with increased incidence of peri-procedural and long-term complications and worse prognosis. Novel antidiabetic agents have represented a paradigm shift in managing patients with diabetes and cardiovascular diseases. However, limited data are reported so far in patients undergoing coronary stenting. This review intends to provide an overview of the biological mechanisms underlying hyperglycaemia-induced vascular damage and the contrasting actions of new antidiabetic drugs. We summarize existing evidence on the effects of these drugs in the setting of PCI, addressing pre-clinical and clinical studies and drug-drug interactions with antiplatelet agents, thus highlighting new opportunities for optimal long-term management of these patients.     

Trehalose Treatment in Zebrafish Model of Lafora Disease

Mutations in the EPM2A gene encoding laforin cause Lafora disease (LD), a progressive myoclonic epilepsy characterized by drug-resistant seizures and progressive neurological impairment. To date, rodents are the only available models for studying LD; however, their use for drug screening is limited by regulatory restrictions and high breeding costs. To investigate the role of laforin loss of function in early neurodevelopment, and to screen for possible new compounds for treating the disorder, we developed a zebrafish model of LD. Our results showed the epm2a^−/− zebrafish to be a faithful model of LD, exhibiting the main disease features, namely motor impairment and neuronal hyperexcitability with spontaneous seizures. The model also showed increased inflammatory response and apoptotic death, as well as an altered autophagy pathway that occurs early in development and likely contributes to the disease progression. Early administration of trehalose was found to be effective for rescuing motor impairment and neuronal hyperexcitability associated with seizures. Our study adds a new tool for investigating LD and might help to identify new treatment opportunities.     

Solvent Vibrations as a Proxy of the Telomere G-Quadruplex Rearrangements across Thermal Unfolding

G-quadruplexes (G4s) are noncanonical forms of DNA involved in many key genome functions. Here, we exploited UV Resonance Raman scattering to simultaneously explore the vibrational behavior of a human telomeric G4 (Tel22) and its aqueous solvent as the biomolecule underwent thermal melting. We found that the OH stretching band, related to the local hydrogen-bonded network of a water molecule, was in strict relation with the vibrational features of the G4 structure as a function of temperature. In particular, the modifications to the tetrahedral ordering of the water network were strongly coupled to the DNA rearrangements, showing changes in temperature that mirrored the multi-step melting process of Tel22. The comparison between circular dichroism and Raman results supported this view. The present findings provide novel insights into the impact of the molecular environment on G4 conformation. Improving current knowledge on the solvent structural properties will also contribute to a better understanding of the role played by water arrangement in the complexation of G4s with ligands.     

Atrial Fibrillation and Aortic Ectasia as Complications of Primary Aldosteronism: Focus on Pathophysiological Aspects

Primary aldosteronism (PA) is the most common cause of secondary hypertension. A growing body of evidence has suggested that, beyond its well-known effects on blood pressure and electrolyte balance, aldosterone excess can exert pro-inflammatory, pro-oxidant and pro-fibrotic effects on the kidney, blood vessels and heart, leading to potentially harmful pathophysiological consequences. In clinical studies, PA has been associated with an increased risk of cardiovascular, cerebrovascular, renal and metabolic complication compared to essential hypertension, including atrial fibrillation (AF) and aortic ectasia. An increased prevalence of AF in patients with PA has been demonstrated in several clinical studies. Aldosterone excess seems to be involved in the pathogenesis of AF by inducing cardiac structural and electrical remodeling that in turn predisposes to arrhythmogenicity. The association between PA and aortic ectasia is less established, but several studies have demonstrated an effect of aldosterone on aortic stiffness, vascular smooth muscle cells and media composition that, in turn, might lead to an increased risk of aortic dilation and dissection. In this review, we focus on the current evidence regarding the potential role of aldosterone excess in the pathogenesis of AF and aortic ectasia.     

Detection of VAMP Proteolysis by Tetanus and Botulinum Neurotoxin Type B In Vivo with a Cleavage-Specific Antibody

Tetanus and Botulinum type B neurotoxins are bacterial metalloproteases that specifically cleave the vesicle-associated membrane protein VAMP at an identical peptide bond, resulting in inhibition of neuroexocytosis. The minute amounts of these neurotoxins commonly used in experimental animals are not detectable, nor is detection of their VAMP substrate sensitive enough. The immune detection of the cleaved substrate is much more sensitive, as we have previously shown for botulinum neurotoxin type A. Here, we describe the production in rabbit of a polyclonal antibody raised versus a peptide encompassing the 13 residues C-terminal with respect to the neurotoxin cleavage site. The antibody was affinity purified and found to recognize, with high specificity and selectivity, the novel N-terminus of VAMP that becomes exposed after cleavage by tetanus toxin and botulinum toxin type B. This antibody recognizes the neoepitope not only in native and denatured VAMP but also in cultured neurons and in neurons in vivo in neurotoxin-treated mice or rats, suggesting the great potential of this novel tool to elucidate tetanus and botulinum B toxin activity in vivo.