Challenges in Metabolomics-Based Tests,Biomarkers Revealed by Metabolomic Analysis,and the Promise of the Application of Metabolomics in Precision Medicine

Metabolomics helps identify metabolites to characterize/refine perturbations of biological pathways in living organisms. Pre-analytical, analytical, and post-analytical limitations that have hampered a wide implementation of metabolomics have been addressed. Several potential biomarkers originating from current targeted metabolomics-based approaches have been discovered. Precision medicine argues for algorithms to classify individuals based on susceptibility to disease, and/or by response to specific treatments. It also argues for a prevention-based health system. Because of its ability to explore gene–environment interactions, metabolomics is expected to be critical to personalize diagnosis and treatment. Stringent guidelines have been applied from the very beginning to design studies to acquire the information currently employed in precision medicine and precision prevention approaches. Large, prospective, expensive and time-consuming studies are now mandatory to validate old, and discover new, metabolomics-based biomarkers with high chances of translation into precision medicine. Metabolites from studies on saliva, sweat, breath, semen, feces, amniotic, cerebrospinal, and broncho-alveolar fluid are predicted to be needed to refine information from plasma and serum metabolome. In addition, a multi-omics data analysis system is predicted to be needed for omics-based precision medicine approaches. Omics-based approaches for the progress of precision medicine and prevention are expected to raise ethical issues.     

Pipeline of Successive Approximation Converters with Optimum Power Merit Factor

In this paper, we present a low power 12 bit 5 MSPS, successive approximation converter architecture using pipeline technique. The converter consumes 4 mW at the Nyquist rate input with 1.8 V power supply. By combination of pipeline and successive architecture, the entire circuit, simulated at the transistor level in a 0.18 μ CMOS process, achieves a FoM (Figure of Merit) of 0.19 pJ/conversion. Jinghua Li was born in 1973. He received the MSEE and BSEE Degree from College of Electronics and information, Shanghai Jiaotong University and Harbin Engineering University in 1997 and 1994 respectively. He is currently pursuing Ph.D degree in Department of Electrical Engineering, Texas A&M University, College Station, TX, USA. In 1997, he joined Bell Laboratory (China), Lucent Technologies as a member of technical staff. He worked on single-chip HDTV decoder IC and Sonet/SDH SoC for various projects in Murray Hill, NJ, USA and Shanghai China. He also finished projects on hardware implementation of Video conference/Phone based on H.263 standard as his master thesis. Since 2000, he has been a research assistant in Analog Mixed Signal center, TAMU. Most currently his research interests are focused on low power analog to digital conversion IC design, CMOS implementation of 10 G/2.5 G clock data recovery IC for high speed serial communications. Franco Maloberti received the Laurea Degree in Physics (Summa cum Laude) from the University of Parma, Parma Italy, in 1968 and the Dr. Honoris Causa degree in electronics from the Instituto Nacional de Astrofisica, Optica y Electronica (Inaoe), Puebla, Mexico in 1996. In 1993 he was a Visiting Professor at ETH-PEL, Zurich. He was Professor of Microelectronics and Head of the Micro Integrated Systems Group University of Pavia, Pavia, Italy and the TI/J.Kilby Analog Engineering Chair Professor at the Texas A&M University. He is currently the Distinguished Microelectronic Chair Professor at University of Texas at Dallas and part-time Professor at the University of Pavia, Italy. His professional expertise is in the design, analysis and characterization of integrated circuits and analogue digital applications, mainly in the areas of switched capacitor circuits, data converters, interfaces for telecommunication and sensor systems, and CAD for analogue and mixed A-D design. He has written more than 250 published papers, three books and holds 15 patents. He was in 1992 recipient of the XII Pedriali Prize for his technical and scientific contributions to national industrial production. He was co-recipient of the 1996 Institute of Electrical Engineers (U.K.) Fleming Premium for the paper “CMOS Triode Transistor Transconductor for high-frequency continuous time filters.” He has been responsible at both technical and management levels for many research programs including ten ESPRIT projects and has served the European Commission as ESPRIT Projects' Evaluator, Reviewer and as European Union expert in many European Initiatives. He served the Academy of Finland on the assessment of electronic research in Academic institutions and on the research programs' evaluations. Dr. Maloberti was Vice-President, Region 8, of the IEEE Circuit and Systems Society from 1995 to 1997 and an Associate Editor of IEEE-Transaction on Circuit and System-II. He received the 1999 IEEE CAS Society Meritorious Service Award, the 2000 CAS Society Golden Jubilee Medal, and the IEEE Millenium Medal. He is the President of the IEEE Sensor Council and member of the Board of Governors of the IEEE CAS Society. He is a member of the Italian Electrothecnical and Electronic Society (AEI), the Editorial Board of Analog Integrated Circuits and Signal Processing, and Fellow of IEEE.     

Focused Design of Novel Cyclic Peptides Endowed with GABARAP-Inhibiting Activity

(1) Background: Disfunctions in autophagy machinery have been identified in various conditions, including neurodegenerative diseases, cancer, and inflammation. Among mammalian autophagy proteins, the Atg8 family member GABARAP has been shown to be greatly involved in the autophagy process of prostate cancer cells, supporting the idea that GABARAP inhibitors could be valuable tools to fight the progression of tumors. (2) Methods: In this paper, starting from the X-ray crystal structure of GABARAP in a complex with an AnkirinB-LIR domain, we identify two new peptides by applying in silico drug design techniques. The two ligands are synthesized, biophysically assayed, and biologically evaluated to ascertain their potential anticancer profile. (3) Results: Two cyclic peptides (WC8 and WC10) displayed promising biological activity, high conformational stability (due to the presence of disulfide bridges), and K_d values in the low micromolar range. The anticancer assays, performed on PC-3 cells, proved that both peptides exhibit antiproliferative effects comparable to those of peptide K1, a known GABARAP inhibitor. (4) Conclusions: WC8 and WC10 can be considered new GABARAP inhibitors to be employed as pharmacological tools or even templates for the rational design of new small molecules.     

Identification of unbalance forces by metaheuristic search algorithms

This paper discusses the identification of parameters in rotary systems, namely, the unbalance magnitude, phase and position in the rotor system. These parameters can be identified using the measured orbits in the hydrodynamic bearings. The oil film forces are evaluated in the different positions of the orbit of the journal and are applied to the model of the shaft. The model, integrated in time domain, allows with an assumed unbalance, to simulate the orbits. The objective function is basically the difference between measured and simulated orbits, and its minimum corresponds to the identified unbalance amount, phase and position along the shaft. With respect to traditional model based identification procedures, this approach using oil film forces instead of oil film linearized stiffness and damping coefficients, and unfiltered orbits instead of 1X vibration components is suitable to deal with non-linear behaviour of the system.     

Simulation of retronasal aroma of white and red wine in a model mouth system. Investigating the influence of saliva on volatile compound concentrations

The influence of saliva on aroma release from white and red wines was studied in a model mouth system. Aroma compounds were analysed in the dynamic headspace of wines by solid phase micro extraction/gas chromatography with flame ionization detection. Volatile compounds were identified by solid phase micro extraction/gas chromatography-mass spectrometry, resulting in a total of 43 compounds in white wine and 41 in red wine. The results showed a greater influence of saliva on aroma release in white wine than red wine. In white wine treated with human saliva, esters and fusel alcohols, responsible for fruity and fusel oil odours, were reduced of 32–80%; by contrast, the concentration of 2-phenylethanol and furfural, responsible for rose and toasted almond notes, increased by 27% and by 155%, respectively. In red wine, treated with human saliva, only a few esters decrease, with a reduction of 22–51% due to protein-binding ability of polyphenols that are able to inhibit the activity of the saliva. C-13 norisoprenoids, vitispirane (eucalyptol) and TDN (kerosene), decreased both in white and red wine, showing a comparable variation while, for β-damascenone, the variation was insignificant.     

High‐tuning‐range CMOS band‐pass IF filter based on a low‐Q cascaded biquad optimization technique

A design procedure for high‐order continuous‐time intermediate‐frequency band‐pass filters based on the cascade of low‐Q biquadratic cells is presented. The approach is well suited for integrated‐circuit fabrication, as it takes into account the maximum capacitance spread dictated by the available technology and maximum acceptable sensitivity to component variations. A trade‐off between noise and maximum linear range is also met. A novel, wide‐tuning‐range transconductor topology is also described. Based on these results, a 10‐pole band‐pass filter for a code division multiple‐access satellite receiver has been designed and tested. The filter provides tunable center frequency (f₀) from 10 to 70 MHz and exhibits a 28‐MHz bandwidth around f₀ = 70 MHz with more than 39‐dB attenuation at f₀/2 and 2f₀. Third‐order harmonic rejection is higher than 60 dB for a 1‐Vpp 70‐MHz input, and equivalent output noise is lower than 1 mV_rms. The circuit is fabricated in a 0.25‐µm complementary metal oxide semiconductor process, and the core consumes 12 mA from a 2.5‐V supply, offering the best current/pole ratio figure. The die area resulted to be 0.9 × 1.1 mm². Copyright © 2014 John Wiley & Sons, Ltd.     

Digital light processing stereolithography of hydroxyapatite scaffolds with bone-like architecture,permeability, and mechanical properties

This work deals with the additive manufacturing and characterization of hydroxyapatite scaffolds mimicking the trabecular architecture of cancellous bone. A novel approach was proposed relying on stereolithographic technology, which builds foam-like ceramic scaffolds by using three-dimensional (3D) micro-tomographic reconstructions of polymeric sponges as virtual templates for the manufacturing process. The layer-by-layer fabrication process involves the selective polymerization of a photocurable resin in which hydroxyapatite particles are homogeneously dispersed. Irradiation is performed by a dynamic mask that projects blue light onto the slurry. After sintering, highly-porous hydroxyapatite scaffolds (total porosity ~0.80, pore size 100-800 µm) replicating the 3D open-cell architecture of the polymeric template as well as spongy bone were obtained. Intrinsic permeability of scaffolds was determined by measuring laminar airflow alternating pressure wave drops and was found to be within 0.75-1.74 × 10⁻⁹ m², which is comparable to the range of human cancellous bone. Compressive tests were also carried out in order to determine the strength (~1.60 MPa), elastic modulus (~513 MPa) and Weibull modulus (m = 2.2) of the scaffolds. Overall, the fabrication strategy used to print hydroxyapatite scaffolds (tomographic imaging combined with digital mirror device [DMD]-based stereolithography) shows great promise for the development of porous bioceramics with bone-like architecture and mass transport properties.