Regulatory Noncoding and Predicted Pathogenic Coding Variants of CCR5 Predispose to Severe COVID-19

Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P ≤ 1 × 10⁻⁵) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5.     

Preliminary Investigation on the Involvement of Cytoskeleton-Related Proteins,DAAM1 and PREP,in Human Testicular Disorders

Herein, for the first time, the potential relationships between the cytoskeleton-associated proteins DAAM1 and PREP with different testicular disorders, such as classic seminoma (CS), Leydig cell tumor (LCT), and Sertoli cell-only syndrome (SOS), were evaluated. Six CS, two LCT, and two SOS tissue samples were obtained during inguinal exploration in patients with a suspect testis tumor based on clinical examination and ultrasonography. DAAM1 and PREP protein levels and immunofluorescent localization were analyzed. An increased DAAM1 protein level in CS and SOS as compared to non-pathological (NP) tissue was observed, while LCT showed no significant differences. Conversely, PREP protein level increased in LCT, while it decreased in CS and SOS compared to NP tissue. These results were strongly supported by the immunofluorescence staining, revealing an altered localization and signal intensity of DAAM1 and PREP in the analyzed samples, highlighting a perturbed cytoarchitecture. Interestingly, in LCT spermatogonia, a specific DAAM1 nuclear localization was found, probably due to an enhanced testosterone production, as confirmed by the increased protein levels of steroidogenic enzymes. Finally, although further studies are needed to verify the involvement of other formins and microtubule-associated proteins, this report raised the opportunity to indicate DAAM1 and PREP as new potential markers, supporting the cytoskeleton dynamics changes occurring during normal and/or pathological cell differentiation.     

Kuwanon‐L as a New Allosteric HIV‐1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation

HIV‐1 integrase (IN) active site inhibitors are the latest class of drugs approved for HIV treatment. The selection of IN strand‐transfer drug‐resistant HIV strains in patients supports the development of new agents that are active as allosteric IN inhibitors. Here, a docking‐based virtual screening has been applied to a small library of natural ligands to identify new allosteric IN inhibitors that target the sucrose binding pocket. From theoretical studies, kuwanon‐L emerged as the most promising binder and was thus selected for biological studies. Biochemical studies showed that kuwanon‐L is able to inhibit the HIV‐1 IN catalytic activity in the absence and in the presence of LEDGF/p75 protein, the IN dimerization, and the IN/LEDGF binding. Kuwanon‐L also inhibited HIV‐1 replication in cell cultures. Overall, docking and biochemical results suggest that kuwanon‐L binds to an allosteric binding pocket and can be considered an attractive lead for the development of new allosteric IN antiviral agents.     

Electroosmotic transport in porous construction materials and dehumidification of masonry

Techniques based on electroosmosis have been proposed as restoration methods to reduce the moisture content in masonry subjected to capillary suction. Although several applications have been reported in the literature and beneficial effects of electroosmosis are often claimed, very little technical information is available. Quite rarely quantitative measurements of humidity changes in the masonry following the application of the current are reported. This paper reports the results of a research work aimed at studying the electroosmotic transport through porous construction materials, in order to investigate the factors that influence electroosmosis and define its actual technological applicability for the rehabilitation of damp masonry. The experimental tests showed that, for several concomitant circumstances, the chances that the technique based on electroosmosis might be effective in drying damp masonry are extremely low.     

Radiant floors integrated with PCM for indoor temperature control

The control of indoor thermal comfort in buildings through thermal inertia during the summer season plays a fundamental role in the design of energy efficient buildings, especially in the Mediterranean climate. In fact, lightweight, highly insulated buildings cannot provide the necessary mass to buffer thermal gains. Phase change materials (PCM) have been used to provide lightweight building components with the required thermal inertia without increasing their overall mass. So far the integration of PCM into lightweight piped radiant floors for the control of thermal comfort during summer cooling regimes has not been investigated. This paper reports the development of a lightweight piped radiant floor prototype with an integrated PCM layer aimed at buffering internal gains at constant temperature during summer cooling regimes without affecting its winter warming capacity. Both the construction of the laboratory specimens and the development of the optimized finite element models are detailed and the assessment of the floor performance in a simulated room is discussed.     

A voltage controlled CMOS current divider with linear characteristic

A compact voltage controlled CMOS current divider is presented. Differently from previous implementations, exploiting the MOSFET translinear characteristics in subthreshold region, the proposed circuit is based on devices operating from moderate to strong inversion. An input current linearity range of nearly a decade is obtained by compensating for the deviations from the ideal drain current square-law approximation through an original empirical approach. The circuit is suitable for use as a building block in analog multipliers and for transconductor continuous tuning. The effectiveness of the proposed configuration is demonstrated by means of electrical simulations, performed on a prototype designed with a commercial process. The robustness of the linearization algorithm with respect to temperature variations is proven.     

Corrosion assessment and restoration strategies of reinforced concrete buildings of the cultural heritage

Since the beginning of the 20th century, in Italy as in many other countries, reinforced concrete (RC) became one of the most popular construction materials and it was used for buildings, monuments, infrastructures, etc. Several of these structures, although of recent formation, have now been included in the cultural heritage, because of their architectural or social relevance. As a consequence of the typical urban or rural exposure conditions of these buildings, they often suffer damage due to carbonation‐induced corrosion of reinforcement, such as concrete spalling or cracking or rust stains that may affect the serviceability of structures. Furthermore, chloride‐induced corrosion of reinforcement, may also concern buildings exposed to de‐icing salts or marine environments. Due to strict requirements related to the preservation of the original materials and texture, the repair of structures that belong to the cultural heritage cannot rely on the conventional repair technique, based on the replacement of carbonated concrete. Therefore, the conservation of RC buildings of the cultural heritage is a challenge, since it requires the development of specific strategies aimed at finding the best compromise between, on one hand, the restoration of structural safety and the prevention of future damage and, on the other hand, the preservation of the original materials and surfaces. This paper analyses the results of inspections carried out on several buildings, built in Italy throughout the 20th century in different micro‐ and macro‐climates, with the aim of showing their peculiarities with regard to steel corrosion and the selection of restorations strategies.     

An Observational Theory for Mobile Ad Hoc Networks (full version)

We propose a process calculus to study the behavioural theory of Mobile Ad Hoc Networks. The operational semantics of our calculus is given both in terms of a Reduction Semantics and in terms of a Labelled Transition Semantics. We prove that the two semantics coincide. The labelled transition system is then used to derive the notions of (weak) simulation and bisimulation for ad hoc networks. The labelled bisimilarity completely characterises reduction barbed congruence, a standard branching-time and contextually-defined program equivalence. We then use our (bi)simulation proof method to formally prove a number of non-trivial properties of ad hoc networks.     

Design,estimation and experimental validation of optical Polarization Mode Dispersion Compensator in 40 Gbit/s NRZ and RZ optical systems

Polarization Mode Dispersion (PMD) compensation has been a matter of investigation of several papers in literature. The proposed solutions belong basically to two large families: electronic compensators and optical compensators. Both PMD compensator schemes have advantages and disadvantages: electronic PMD compensators are usually simple to include in line-terminal, potentially low-cost, very fast, and FEC compatible but their development is strongly dependent on IC technology capability that at this time allows device developments up to the 10 Gbit/s bit rates area. Furthermore, they are strongly dependent on modulation formats, and they can operate only on a single channel. Conversely, optical compensators are independent of bit rate and modulation format and potentially they can compensate more channels simultaneously; their major drawbacks are the longer response time and the complexity in the feedback signal process within the control algorithm. In this paper we consider an optical Polarization Mode Dispersion Compensator (PMDC) that is simple to realize and easy to include at limited costs in each EDFA module (distributed compensation) as well as a single-stage front-end compensator. Numerical analysis of the PMDC and experimental results confirm the utility of the PMDC proposed and its capability in compensating DGD larger than 20 ps in NRZ and RZ 40 Gbit/s optical systems.