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.     

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.     

Ultra-High Energy Cosmic Particles studies from space: , a possible next-generation experiment

After the Pierre Auger Observatory, it is likely that space-based experiments might be required for next-generation studies of Ultra-High Energy Cosmic Particles. An overview of this challenging task is presented, emphasizing the main design issues, the criticalities and the intermediate steps required to make this challenging task a reality.     

Nonsimple isotropic incompressible linear fluids surrounding one-dimensional structures

We introduce a model of fluid which has four main features: it readily emerges by a general continuum mechanical framework; it is a generalization maintaining most of the physical features of incompressible Newtonian fluids; it can model adherence interactions with one-dimensional structures surrounded by the fluid; the associated initial boundary-value problem is well-posed on three-dimensional domains.     

Formalizing REST APIs for web-based communication and SIP interworking

This paper proposes an instantaneous recovery route design scheme using multiple coding-aware link protection scenarios to achieve higher link cost reduction in the network. In this scheme, two protection scenarios, namely, (i) traffic splitting (TS), and (ii) two sources and a common destination (2SD) are used to integrate multiple sources and a common destination. The proposed scheme consists of two phases. In the first phase, the proposed scheme determines routes for 2SD and TS scenarios of all possible source-destination pairs to minimize the total link cost. In this phase, the network coding is applied to the common path within each scenario, individually. In the second phase, network coding is applied to the common path between two scenarios (or a scenario pair) in order to enhance the resource saving. This phase develops conditions that select the most appropriate combination of scenario pairs, such as TS–TS, 2SD–2SD, and 2SD–TS for network coding, including their proofs. Using these conditions, a heuristic algorithm is introduced in order to select the most appropriate combination of scenario pairs for further enhancing of resource saving. Simulation results show that the proposed scheme outperforms the conventional 1 + 1 protection scheme, the TS scenario, and the 2SD scenario in terms of link cost reduction in the network.     

Exploiting capture and interference cancellation for uplink random multiple access in 5G millimeter-wave networks

The forthcoming 5G technology aims to provide massive device connectivity and ultra-high capacity with reduced latency and costs. These features will be enabled by increasing the density of the base stations, using millimeter-wave (mmWave) bands, massive multiple-input multiple-output systems, and non-orthogonal multiple access techniques. The ability to support a large number of terminals in a small area is in fact a great challenge to guarantee massive access. In this context, this paper proposes a new receiver model for the uplink of 5G mmWave cellular networks. The receiver, called Iterative Decoding and Interference Cancellation (IDIC), is based on the Slotted Aloha (SA) protocol and exploits the capture effect alongside the successive IC process to resolve packet collisions. A 5G propagation scenario, modeled according to recent mmWave channel measurements, is used to compare IDIC with the widely adopted Contention Resolution Diversity SA (CRDSA) scheme to show the performance gain of IDIC, when elements of practical relevance, like imperfect cancellation and receive power diversity, are considered. The impact of packet and power diversity is also investigated to derive the preferable uplink random access strategy that maximizes the system throughput according to the offered channel load.

     

Gyroid‐Structured 3D ZnO Networks Made by Atomic Layer Deposition

3D continuous ZnO morphologies with characteristic feature sizes on the 10 nm length scale are attractive for electronic device manufacture. However, their synthesis remains a challenge because of the low crystallization temperature of ZnO. Here, we report a method for the robust and reliable synthesis of fully crystalline 3D mesoporous ZnO networks by means of atomic layer deposition (ALD) of ZnO into a self‐assembled block copolymer template. By carefully optimizing the processing conditions we are able to synthesize several‐micrometer‐thick layers of mesoporous ZnO networks with a strut width of 30 nm. Two 3D mesoporous morphologies are manufactured: a periodic gyroid structure and a random worm‐like morphology. Exploiting the ALD property to conformally coat complex surfaces of high aspect ratio, the channel network of a 3D continuous channel network of a self‐assembled block copolymer is replicated into ZnO. X‐ray photoemission spectroscopy and x‐ray diffraction measurements reveal that the chemical composition of the mesoporous structures is uniform and consists of wurtzite‐ZnO throughout the film. Scanning electron microscopy reveals an average pore dimension of 30 nm. The potential of this material for a hybrid photovoltaic application is demonstrated by the manufacture of a poly(3‐hexylthiophene)/ZnO solar cell.     

A 5-GHz highly integrated receiver front-end

In this paper a radio front-end for a IEEE 802.11a and HIPERLAN2 sliding-IF receiver is presented. The circuit, implemented in a low-cost 46-GHz-f _T silicon bipolar process, includes a variable-gain low noise amplifier and a double-balanced mixer. Thanks to monolithic LC filters and on-chip single-ended-to-differential conversion of the RF signal, the proposed solution does not require the expensive image rejection filter and an external input balun. The receiver front-end exhibits a 4.3-dB noise figure and a power gain of 21 dB, providing an image rejection ratio higher than 50 dB. By using a 1-bit gain control, it achieves an input 1-dB compression point of −11 dBm, while drawing only 22 mA from a 3-V supply voltage.     

Hybrid Nanodielectrics for Low‐Voltage Organic Electronics

Nanoscale hybrid dielectrics composed of an ultra‐thin polymeric low‐κ bottom layer and an ultra‐thin high‐κ oxide top layer, with high dielectric strength and capacitances up to 0.25 μFcm^?2, compatible with low‐voltage, low‐power, organic electronic circuits are demonstrated. An efficient and reliable fabrication process, with 100% yield achieved on lab‐scale arrays, is demonstrated by means of pulsed laser deposition (PLD) for the fast growth of the oxide layer. With this strategy, high capacitance top gate (TG), n‐type and p‐type organic field effect transistors (OFETs) with high mobility, low leakage currents, and low subthreshold slopes are realized and employed in complementary‐like inverters, exhibiting ideal switching for supply voltages as low as 2 V. Importantly, the hybrid double‐layer allows for a neat decoupling between the need for a high capacitance, guaranteed by the nanoscale thickness of the double layer, and for an optimized semiconductor–dielectric interface, a crucial point in enabling high mobility OFETs, thanks to the low‐κ polymeric dielectric layer in direct contact with the polymer semiconductor. It is shown that such decoupling can be achieved already with a polymer dielectric as thin as 10 nm when the top oxide is deposited by PLD. This paves the way for a very versatile implementation of the proposed approach for the scaling of the operating voltages of TG OFETs with very low level of dielectric leakage currents to the fabrication of low‐voltage organic electronics with drastically reduced power consumption.