CMOS Non‐tailed differential pair

A continuous‐time complementary metal–oxide–semiconductor differential pair that does not require the traditional tail current source as a way to control the direct current and common‐mode current is presented. Compared with a p‐channel long‐tailed pair, the proposed non‐tailed solution operates under a higher maximum input common‐mode voltage that includes (V_DD + V_SS)/2 even under low supply voltages. Experimental measurements on a prototype fabricated in a 0.35‐µm technology (with metal – oxide – semiconductor thresholds greater than 0.6 V) confirm this behavior for supply voltages as low as 1.2 V, whereas the long‐tailed pair with the same technology offers the same capability only for supplies higher than 1.6 V. Copyright © 2015 John Wiley & Sons, Ltd.     

Elastic Properties and Structure of Interpenetrating Boron Carbide/Aluminum Multiphase Composites

We study the elastic moduli and structure of boron carbide/aluminum (B₄C/Al) multiphase composites using rigorous bounding and experimental characterization techniques. We demonstrate that rigorous bounds on the effective moduli are useful in that they can accurately predict (i) the effective elastic moduli, given the phase moduli and volume fractions, or (ii) the phase moduli (volume fractions), given the effective moduli and phase volume fractions (moduli). Using the best available rigorous bounds on the effective elastic moduli of multiphase composites involving volume-fraction information, we are able to predict the bulk and shear moduli of the Al₄BC phase, a reaction product that forms during heat treatment. These theoretical predictions are in very good agreement with recent experimental measurements of the moduli of the Al₄BC phase. Moreover, we evaluate more-refined bounds involving three-point structural correlation functions by extracting such information from an image of a sample of the B₄C/Al composite. Although experimental data for the effective moduli are unavailable for this sample, our predictions of the effective moduli based on three-point bounds should be quite accurate.     

A Life Cycle Assessment of lithium battery and hydrogen-FC powered electric bicycles: Searching for cleaner solutions to urban mobility

Smart mobility is day by day becoming one of the crucial issues to address in order to reduce environmental impacts such as global warming, acidification, photochemical smog, among others. The growing concerns about urban air quality are the driving force for cleaner and more efficient transport systems. Several new transport technologies are being developed, in particular concerning electric vehicles, considered a suitable solution to urban air pollution problems. However, these vehicles require electric and electronic devices that might give rise to a new set of environmental problems in their production, operation and disposal phases. Are electric vehicles a really cleaner solution? This paper aims at answering this question, by comparing two kinds of vehicle, a lithium battery powered electric bike and a hydrogen-fuel cell operated one, using internal combustion engine vehicles as benchmark. The fuel cell bike uses a proton exchange membrane fuel cell (PEMFC) to convert hydrogen into electricity. In this study, Life Cycle Assessment is applied to evaluate the environmental burdens of the production of these two vehicles and compare their environmental performances per 100 km travelled. The study, not only includes vehicle road operation but also embraces production and distribution of bikes, electric battery, PEMFC and energy carriers (electricity and hydrogen) over the vehicle's entire lifetime. The LCA evaluation of the vehicle production phases shows that the construction of the H-bike results more impacting than the E-bike in all the considered categories due to the presence of more complex components technology. Instead, when the boundary is shifted to the operational phases of the vehicles including the energy carriers production, the situation is reversed and the environmental performance of the H-bike results better than the one of E-bike.     

Extracellular Vesicles in Osteosarcoma: Antagonists or Therapeutic Agents?

Osteosarcoma (OS) is a skeletal tumor affecting mainly children and adolescents. The presence of distance metastasis is frequent and it is localized preferentially to the lung, representing the main reason for death among patients. The therapeutic approaches are based on surgery and chemotherapeutics. However, the drug resistance and the side effects associated with the chemotherapy require the identification of new therapeutic approaches. The understanding of the complex biological scenario of the osteosarcoma will open the way for the identification of new targets for its treatment. Recently, a great interest of scientific community is for extracellular vesicles (EVs), that are released in the tumor microenvironment and are important regulators of tumor proliferation and the metastatic process. At the same time, circulating extracellular vesicles can be exploited as diagnostic and prognostic biomarkers, and they can be loaded with drugs as a new therapeutic approach for osteosarcoma patients. Thus, the characterization of OS-related EVs could represent a way to convert these vesicles from antagonists for human health into therapeutic and/or diagnostic agents.     

A 3-GHz microwave imaging system based on a modulated scattering technique and on a modified Born approximation

This article deals with short-range active microwave imaging. In particular, a 3-GHz imaging system based on a modulated scattering technique is described. By using a probe made of an array of (passive) dipoles rotating around a test area, it is possible to measure the field scattered by a long cylinder under approximately transverse-magnetic illumination conditions. Moreover, some considerations are made concerning the relationship for the modulated scattering techniques. Finally, some preliminary experimental results are presented. They were obtained by using a numerical approach to the electromagnetic inverse scattering problem which is developed in the spatial domain, and by making use of a modified Born approximation. © 1998 John Wiley & Sons, Inc. Int J Imaging Syst Technol, 9, 395–403, 1998     

VDACs Post-Translational Modifications Discovery by Mass Spectrometry: Impact on Their Hub Function

VDAC (voltage-dependent anion selective channel) proteins, also known as mitochondrial porins, are the most abundant proteins of the outer mitochondrial membrane (OMM), where they play a vital role in various cellular processes, in the regulation of metabolism, and in survival pathways. There is increasing consensus about their function as a cellular hub, connecting bioenergetics functions to the rest of the cell. The structural characterization of VDACs presents challenging issues due to their very high hydrophobicity, low solubility, the difficulty to separate them from other mitochondrial proteins of similar hydrophobicity and the practical impossibility to isolate each single isoform. Consequently, it is necessary to analyze them as components of a relatively complex mixture. Due to the experimental difficulties in their structural characterization, post-translational modifications (PTMs) of VDAC proteins represent a little explored field. Only in recent years, the increasing number of tools aimed at identifying and quantifying PTMs has allowed to increase our knowledge in this field and in the mechanisms that regulate functions and interactions of mitochondrial porins. In particular, the development of nano-reversed phase ultra-high performance liquid chromatography (nanoRP-UHPLC) and ultra-sensitive high-resolution mass spectrometry (HRMS) methods has played a key role in this field. The findings obtained on VDAC PTMs using such methodologies, which permitted an in-depth characterization of these very hydrophobic trans-membrane pore proteins, are summarized in this review.     

Ncx3-Induced Mitochondrial Dysfunction in Midbrain Leads to Neuroinflammation in Striatum of A53t-α-Synuclein Transgenic Old Mice

The exact mechanism underlying selective dopaminergic neurodegeneration is not completely understood. The complex interplay among toxic alpha-synuclein aggregates, oxidative stress, altered intracellular Ca²⁺-homeostasis, mitochondrial dysfunction and disruption of mitochondrial integrity is considered among the pathogenic mechanisms leading to dopaminergic neuronal loss. We herein investigated the molecular mechanisms leading to mitochondrial dysfunction and its relationship with activation of the neuroinflammatory process occurring in Parkinson’s disease. To address these issues, experiments were performed in vitro and in vivo in mice carrying the human mutation of α-synuclein A53T under the prion murine promoter. In these models, the expression and activity of NCX isoforms, a family of important transporters regulating ionic homeostasis in mammalian cells working in a bidirectional way, were evaluated in neurons and glial cells. Mitochondrial function was monitored with confocal microscopy and fluorescent dyes to measure mitochondrial calcium content and mitochondrial membrane potential. Parallel experiments were performed in 4 and 16-month-old A53T-α-synuclein Tg mice to correlate the functional data obtained in vitro with mitochondrial dysfunction and neuroinflammation through biochemical analysis. The results obtained demonstrated: 1. in A53T mice mitochondrial dysfunction occurs early in midbrain and later in striatum; 2. mitochondrial dysfunction occurring in the midbrain is mediated by the impairment of NCX3 protein expression in neurons and astrocytes; 3. mitochondrial dysfunction occurring early in midbrain triggers neuroinflammation later into the striatum, thus contributing to PD progression during mice aging.     

High Glucose Exposure Impairs L-Cell Differentiation in Intestinal Organoids: Molecular Mechanisms and Clinical Implications

Intestinal organoids are used to analyze the differentiation of enteroendocrine cells (EECs) and to manipulate their density for treating type 2 diabetes. EEC differentiation is a continuous process tightly regulated in the gut by a complex regulatory network. However, the effect of chronic hyperglycemia, in the modulation of regulatory networks controlling identity and differentiation of EECs, has not been analyzed. This study aimed to investigate the effect of glucotoxicity on EEC differentiation in small intestinal organoid platforms. Mouse intestinal organoids were cultured in the presence/absence of high glucose concentrations (35 mM) for 48 h to mimic glucotoxicity. Chronic hyperglycemia impaired the expression of markers related to the differentiation of EEC progenitors (Ngn3) and L-cells (NeuroD1), and it also reduced the expression of Gcg and GLP-1 positive cell number. In addition, the expression of intestinal stem cell markers was reduced in organoids exposed to high glucose concentrations. Our data indicate that glucotoxicity impairs L-cell differentiation, which could be associated with decreased intestinal stem cell proliferative capacity. This study provides the identification of new targets involved in new molecular signaling mechanisms impaired by glucotoxicity that could be a useful tool for the treatment of type 2 diabetes.     

Analytical comparison of reversed nested Miller frequency compensation techniques

In this paper, novel and previously proposed reversed nested Miller compensation (RNMC) networks are analyzed and compared, and their design equations are also presented. Hence, this paper is the natural extension of a previous paper by the authors (Int. J. Circ. Theor. Appl. 2008; 36 (1):53–80), where only the nested Miller compensation topologies were treated. In particular, a coherent and comprehensive analytical comparison of the RNMC topologies, including two new networks presented for the first time, is performed by means of the figure of merit that expresses a trade‐off among gain‐bandwidth product, load capacitance and total transconductance, for equal values of phase margin (Int. J. Circ. Theor. Appl. 2008; 36 (1):53–80). The analysis shows that there is no unique optimal solution among the RNMC topologies, as this depends on the load condition as well as on the relative transconductance magnitude of each amplifier stage. From this point of view, the proposed comparison also outlines useful design guidelines for the optimization of large‐signal and small‐signal performance. Simulations confirming the effectiveness of the proposed design methodology and analytical comparison are also included. Copyright © 2009 John Wiley & Sons, Ltd.