The Endothelium and COVID-19: An Increasingly Clear Link Brief Title: Endotheliopathy in COVID-19

The endothelium has a fundamental role in the cardiovascular complications of coronavirus disease 2019 (COVID-19). Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) particularly affects endothelial cells. The virus binds to the angiotensin-converting enzyme 2 (ACE-2) receptor (present on type 2 alveolar cells, bronchial epithelial cells, and endothelial cells), and induces a cytokine storm. The cytokines tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 have particular effects on endothelial cells—leading to endothelial dysfunction, endothelial cell death, changes in tight junctions, and vascular hyperpermeability. Under normal conditions, apoptotic endothelial cells are removed into the bloodstream. During COVID-19, however, endothelial cells are detached more rapidly, and do not regenerate as effectively as usual. The loss of the endothelium on the luminal surface abolishes all of the vascular responses mediated by the endothelium and nitric oxide production in particular, which results in greater contractility. Moreover, circulating endothelial cells infected with SARS-CoV-2 act as vectors for viral dissemination by forming clusters that migrate into the circulation and reach distant organs. The cell clusters and the endothelial dysfunction might contribute to the various thromboembolic pathologies observed in COVID-19 by inducing the formation of intravascular microthrombi, as well as by triggering disseminated intravascular coagulation. Here, we review the contributions of endotheliopathy and endothelial-cell-derived extracellular vesicles to the pathogenesis of COVID-19, and discuss therapeutic strategies that target the endothelium in patients with COVID-19.     

Low Doses of PFOA Promote Prostate and Breast Cancer Cells Growth through Different Pathways

Endocrine Disrupting Compounds (EDCs) are found in everyday products. Widely distributed throughout the environment, persistent organic pollutants (POPs) are a specific class of EDCs that can accumulate in adipose tissue. Many of them induce adverse effects on human health—such as obesity, fertility disorders and cancers—by perturbing hormone effects. We previously identified many compounds with EDC activity in the circulation of obese patients who underwent bariatric surgery. Herein, we analyzed the effects of four of them (aldrin, BDE28, PFOA and PCB153) on two cancer cell lines of hormone-sensitive organs (prostate and breast). Each cell line was exposed to serial dilutions of EDCs from 10⁻⁶ M to 10⁻¹² M; cytotoxicity and proliferation were monitored using the IncuCyte^® technology. We showed that none of these EDCs induce cytotoxicity and that PFOA and PCB153, only at very low doses (10⁻¹² M), increase the proliferation of DU145 (prostate cancer) and MCF7 (breast cancer) cells, while the same effects are observed with high concentrations (10⁻⁶ M) for aldrin or BDE28. Regarding the mechanistic aspects, PFOA uses two different signaling pathways between the two lines (the Akt/mTORC1 and PlexinD1 in MCF7 and DU145, respectively). Thus, our study demonstrates that even at picomolar (10⁻¹² M) concentrations PFOA and PCB153 increase the proliferation of prostate and breast cancer cell lines and can be considered possible carcinogens.     

Characterization of a Cutibacterium acnes Camp Factor 1-Related Peptide as a New TLR-2 Modulator in In Vitro and Ex Vivo Models of Inflammation

Cutibacterium acnes (C. acnes) has been implicated in inflammatory acne where highly mutated Christie–Atkins–Munch–Petersen factor (CAMP)1 displays strong toll like receptor (TLR)-2 binding activity. Using specific antibodies, we showed that CAMP1 production was independent of C. acnes phylotype and involved in the induction of inflammation. We confirmed that TLR-2 bound both mutated and non-mutated recombinant CAMP1, and peptide array analysis showed that seven peptides (A14, A15, B1, B2, B3, C1 and C3) were involved in TLR-2 binding, located on the same side of the three-dimensional structure of CAMP1. Both mutated and non-mutated recombinant CAMP1 proteins induced the production of C-X-C motif chemokine ligand interleukin (CXCL)8/(IL)-8 in vitro in keratinocytes and that of granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor (TNF)-α, IL-1β and IL-10 in ex vivo human skin explants. Only A14, B1 and B2 inhibited the production of CXCL8/IL-8 by keratinocytes and that of (GM-CSF), TNF-α, IL-1β and IL-10 in human skin explants stimulated with rCAMP1 and C. acnes. Following pretreatment with B2, RNA sequencing on skin explants identified the 10 genes displaying the strongest differential expression as IL6, TNF, CXCL1, CXCL2, CXCL3, CXCL8, IL-1β, chemokine ligand (CCL)2, CCL4 and colony stimulating factor (CSF)2. We, thus, identified a new CAMP1-derived peptide as a TLR-2 modulator likely to be a good candidate for clinical evaluation.     

Reference classes: a tool for benchmarking universities’ research

Based on new comparison principles that take into account both the volume of scientific production and its impact, this paper proposes a method for defining reference classes of universities. Several tools are developed in order to enable university managers to define the value system according to which their university shall be compared to others. We apply this methodology to French universities and illustrate it using the reference classes of the best ranked universities according to several value systems.     

A linear 60 GHz 65 nm-CMOS power amplifier realization and characterization for OFDM signal

A millimeter-wave Power Amplifier (PA) based on a 65nm CMOS technology from STMicroelectronics has been designed. The targeted feature is the unlicensed band around 60 GHz suitable for wireless personal area network application (WPAN). To optimize the linearity, the PA is designed under class A biasing to have an output compression point (OCP₁) close to its saturated Power (P _sat). S-parameters and large signal measurement results are demonstrated and compared with electromagnetic simulations. The PA offers a P _sat of 8.3 dBm, an OCP₁ of 6 dBm and a gain of 6.7 dB. The die area is 0.29 mm² with pads. Considering those results, one-tone simulations are not sufficient to characterize the linearity performances of the PA in its real conditions of use. Consequently, two-tone simulations are firstly performed. After, linearity figures of merit (FoM) are discussed applying an orthogonal frequency-division multiplexing (OFDM) modulated signal. The PA offers an adjacent channel power ratio (ACPR) of 15 dB and an error vector magnitude (EVM) of 20% at PA compression operating mode.     

Analysis of the musculoskeletal system of the hand and forearm during a cylinder grasping task

Musculoskeletal disorders of the hand are mostly due to repeated or awkward manual tasks in the work environment and are considered a public health issue. To prevent their development, it is necessary to understand and investigate the biomechanical behavior of the musculoskeletal system during the movement. In this study a biomechanical analysis of the upper extremity during a cylinder grasping task is conducted by using a parameterized musculoskeletal model of the hand and forearm. The proposed model is composed of 21 segments, 28 musculotendon units, and 20 joints providing 24 degrees of freedom. Boundary conditions of the model are defined by the three-dimensional coordinates of 43 external markers fixed to bony landmarks of the hand and forearm and tracked with an optoelectronic motion capture system. External marker positions from five healthy participants were used to test the model. A task consisting of closing and opening fingers around a cylinder 25 mm in diameter was investigated. Based on experimental kinematic data, an inverse dynamics process was performed to calculate output data of the model (joint angles, musculotendon unit shortening and lengthening patterns). Finally, based on an optimization procedure, joint loads and musculotendon forces were computed in a forward dynamics simulation. Results of this study assessed reproducibility and consistency of the biomechanical behavior of the musculoskeletal hand system.     

A comparative study of hardware architectures for lightweight block ciphers

A hardware-based performance comparison of lightweight block ciphers is conducted in this paper. The DESL, DESXL, CURUPIRA-1, CURUPIRA-2, HIGHT, PUFFIN, PRESENT and XTEA block ciphers have been employed in this comparison. Our objective is to survey what ciphers are suitable for security in Radio Frequency Identification (RFID) and other security applications with demanding area restrictions. A general architecture option has been followed for the implementation of all ciphers. Specifically, a loop architecture has been used, where one basic round is used iteratively. The basic performance metrics are the area, power consumption and hardware resource cost associated with the implementation resulting throughput of each cipher. The most compact cipher is the 80-bit PRESENT block cipher with a count of 1704 GEs and 206.4 Kbps, while the largest in area cipher is the CURUPIRA-1. The CURUPIRA-1 cipher consumes the highest power of 118.1 μW, while the PRESENT cipher consumes the lowest power of 20 μW. All measurements have been taken at a 100 kHz clock frequency.     

Motorcyclists’ speed and “looked-but-failed-to-see” accidents

Previous research on motorcycle crashes has shown the frequency and severity of accidents in which a non-priority road user failed to give way to an approaching motorcyclist without seeing him/her, even though the road user had looked in the approaching motorcycle's direction and the motorcycle was visible. These accidents are usually called “looked-but-failed-to-see” (LBFS) accidents. This article deals with the effects that the motorcyclist's speed has in these accidents. It is based on the in-depth study and precise kinematic reconstruction of 44 accident cases involving a motorcyclist and another road user, all occurring in intersections. The results show that, in urban environments, the initial speeds of motorcyclists involved in “looked-but-failed-to-see” accidents are significantly higher than in other accidents at intersections. In rural environments, the difference in speed between LBFS accidents and other accidents is not significant, but further investigations would be necessary to draw any conclusions. These results suggest that speed management, through road design or by other means, could contribute to preventing “looked-but-failed-to-see” motorcycle accidents, at least in urban environments.