Deep learning and embeddings for problems of computational biology

The development of Next Generation Sequencing promotes Biology in the Big Data era. The ever-increasing gap between proteins with known sequences and those with a complete functional annotation requires computational methods for automatic structure and functional annotation. My research has been focusing on proteins and led so far to the development of three novel tools, DeepREx, E-SNPs&GO and ISPRED-SEQ, based on Machine and Deep Learning approaches. DeepREx computes the solvent exposure of residues in a protein chain. This problem is relevant for the definition of structural constraints regarding the possible folding of the protein. DeepREx exploits Long Short-Term Memory layers to capture residue-level interactions between positions distant in the sequence, achieving state-of-the-art performances. With DeepRex, I conducted a large-scale analysis investigating the relationship between solvent exposure of a residue and its probability to be pathogenic upon mutation. E-SNPs&GO predicts the pathogenicity of a Single Residue Variation. Variations occurring on a protein sequence can have different effects, possibly leading to the onset of diseases. E-SNPs&GO exploits protein embeddings generated by two novel Protein Language Models (PLMs), as well as a new way of representing functional information coming from the Gene Ontology. The method achieves state-of-the-art performances and is extremely time-efficient when compared to traditional approaches. ISPRED-SEQ predicts the presence of Protein-Protein Interaction sites in a protein sequence. Knowing how a protein interacts with other molecules is crucial for accurate functional characterization. ISPRED-SEQ exploits a convolutional layer to parse local context after embedding the protein sequence with two novel PLMs, greatly surpassing the current state-of-the-art. All methods are published in international journals and are available as user-friendly web servers. They have been developed keeping in mind standard guidelines for FAIRness (FAIR: Findable, Accessible, Interoperable, Reusable) and are integrated into the public collection of tools provided by ELIXIR, the European infrastructure for Bioinformatics

Quaterpyridine Ligands for Panchromatic Ru(II) Dye Sensitizers

A new general synthetic access to carboxylated quaterpyridines (qpy), of interest as ligands for panchromatic dyesensitized solar cell organometallic sensitizers, is presented. The strategic step is a Suzuki−Miyaura cross-coupling reaction, which has allowed the preparation of a number of representative unsubstituted and alkyl and (hetero)aromatic substituted qpys. To bypass the poor inherent stability of 2-pyridylboronic acid derivatives, we successfully applied N-methyliminodiacetic acid (MIDA) boronates as key reagents, obtaining the qpy ligands in good yields up to (quasi)gram quantities. The structural, spectroscopic (NMR and UV−vis), electrochemical, and electronic characteristics of the qpy have been experimentally and computationally (DFT) investigated. The easy access to the bis-thiocyanato Ru(II) complex of the parent species of the qpy series, through an efficient route which bypasses the use of Sephadex column chromatography, is shown. The bis-thiocyanato Ru(II) complex has been spectroscopically (NMR and UV−vis), electrochemically, and computationally investigated, relating its properties to those of previously reported Ru(II)−qpy complexes.“This document is the Accepted Manuscript version of a Published Work that appeared in final form in [The Journal of Organic Chemistry], copyright © American Chemical Society after peer review and technical editing by the publisher

3D printed lattice metal structures for enhanced heat transfer in latent heat storage systems

The low thermal conductivity of Phase Change Materials (PCMs), e.g., paraffin waxes, is one of the main drawbacks of latent heat storage, especially when fast charging and discharging cycles are required. The introduction of highly conductive fillers in the PCM matrix may be an effective solution; however, it is difficult to grant their stable and homogeneous dispersion, which therefore limits the resulting enhancement of the overall thermal conductivity. Metal 3D printing or additive manufacturing, instead, allows to manufacture complex geometries with precise patterns, therefore allowing the design of optimal paths for heat conduction within the PCM. In this work, a device-scale latent heat storage system operating at medium temperatures (∼ 90 °C) was manufactured and characterized. Its innovative design relies on a 3D Cartesian metal lattice, fabricated via laser powder bed fusion, to achieve higher specific power densities. Numerical and experimental tests demonstrated remarkable specific power (approximately 714 ± 17 W kg−1 and 1310 ± 48 W kg−1 during heat charge and discharge, respectively). Moreover, the device performance remained stable over multiple charging and discharging cycles. Finally, simulation results were used to infer general design guidelines to further enhance the device performance. This work aims at promoting the use of metal additive manufacturing to design efficient and responsive thermal energy storage units for medium-sized applications, such as in the automotive sector (e.g. speed up of the engine warm up or as an auxiliary for other enhanced thermal management strategies

Stability of Oscillating Gaseous Masses in Massive Brans-Dicke Gravity

This paper explores the instability of gaseous masses for the radial oscillations in post-Newtonian correction of massive Brans-Dicke gravity. For this purpose, we derive linearized perturbed equation of motion through Lagrangian radial perturbation which leads to the condition of marginal stability. We discuss radius of instability of different polytropic structures in terms of the Schwarzschild radius. It is concluded that our results provide a wide range of difference with those in general relativity and Brans-Dicke gravity.Comment: 31 pages, 11 figures, to appear in IJMP

Laparoscopic Nephron-Sparing Calycectomy for Treating Fraley's Syndrome

Background/Aims/Objectives: Various nephron-sparing approaches were described as part of surgical management for Fraley's syndrome, a rare anatomic variant of the renal vascular anatomy that compresses the upper pole infundibulum resulting in an upper calyceal obstruction and dilatation, with symptoms of flank pain and hematuria. To date, descriptions of minimally invasive correction techniques are anecdotal. METHODS: A retroperitoneal pure laparoscopic approach using the nephron-sparing technique was chosen in the presented case. RESULTS: In this report, we demonstrated that if laparoscopic calycectomy is performed without clamping of renal branches, parenchymal ischemia can be completely avoided. Additionally, the preservation of renal tissue surrounding the calyx enables the preservation of the intrasinusal segmental arteries flow, thereby avoiding their accidental closure by hemostatic sutures. CONCLUSIONS: In conclusion, Laparoscopic Nephron-Sparing Calycectomy is a safe and effective surgical procedure for the treatment of Fraley's syndrome. Consistent laparoscopic experience is required before embarking on this kind of surgery

A 5-year retrospective longitudinal study on the incidence and the risk factors of osteonecrosis of the jaws in patients treated with zoledronic acid for bone metastases from solid tumors

Background: The aim of this study was to evaluate the incidence and the risk factors of osteonecrosis of the jaw (ONJ) in a group of patients treated with zoledronic acid (ZA) for bone metastases from solid tumors and enrolled in a preventive dental program. Material and Methods: This 5-year retrospective longitudinal study included all consecutive oncological patients who underwent at least one infusion with ZA between 2004 and 2011 for bone metastases due to solid neoplasms. Results: Of the 156 patients enrolled in the study, 17 developed ONJ (10.89%). At the multivariate analysis, severe periodontal disease (P=0.025), tooth extraction (P<0.0001) and starting the preventive dental program after the beginning of ZA therapy (P=0.02) were the only factors which showed a significant association with the occurrence of ONJ. Conclusions: This study demonstrated the importance of beginning dental prevention before zoledronic acid exposure in reducing ONJ occurrence, especially in the long term. The results of this research show that control of periodontal disease and an increase in the time between tooth extraction and the first ZA administration are recommended in order to reduce the risk of ONJ developmen

Short Heat Treatments for the F357 Aluminum Alloy Processed by Laser Powder Bed Fusion

Conventionally processed precipitation hardening aluminum alloys are generally treated with T6 heat treatments which are time-consuming and generally optimized for conventionally processed microstructures. Alternatively, parts produced by laser powder bed fusion (L-PBF) are characterized by unique microstructures made of very fine and metastable phases. These peculiar features require specifically optimized heat treatments. This work evaluates the effects of a short T6 heat treatment on L-PBF AlSi7Mg samples. The samples underwent a solution step of 15 min at 540 °C followed by water quenching and subsequently by an artificial aging at 170 °C for 2-8 h. The heat treated samples were characterized from a microstructural and mechanical point of view and compared with both as-built and direct aging (DA) treated samples. The results show that a 15 min solution treatment at 540 °C allows the dissolution of the very fine phases obtained during the L-PBF process; the subsequent heat treatment at 170 °C for 6 h makes it possible to obtain slightly lower tensile properties compared to those of the standard T6. With respect to the DA samples, higher elongation was achieved. These results show that this heat treatment can be of great benefit for the industry