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.     

Modified Fluoroquinolones as Antimicrobial Compounds Targeting Chlamydia trachomatis

Chlamydia trachomatis causes the most common sexually transmitted bacterial infection and trachoma, an eye infection. Untreated infections can lead to sequelae, such as infertility and ectopic pregnancy in women and blindness. We previously enhanced the antichlamydial activity of the fluoroquinolone ciprofloxacin by grafting a metal chelating moiety onto it. In the present study, we pursued this pharmacomodulation and obtained nanomolar active molecules (EC₅₀) against this pathogen. This gain in activity prompted us to evaluate the antibacterial activity of this family of molecules against other pathogenic bacteria, such as Neisseria gonorrhoeae and bacteria from the ESKAPE group. The results show that the novel molecules have selectively improved activity against C. trachomatis and demonstrate how the antichlamydial effect of fluoroquinolones can be enhanced.     

An integrated on chip organic optical source based on electrochemiluminescence

We report here on an original “glass-PDMS-glass” electrochemiluminescence optofluidic device that integrates 32 electrodes on a large surface. This organic electrically powered light source has been integrated on chip using an alternative process based on a photopatternable silicone resist. Under a continuous flow rate, this device allows electrogenerated chemiluminescence for several minutes which would be very useful for future μTAS systems.     

Energy Aware Signal Processing for Software Defined Radio Baseband Implementation

The fast pacing diversity and evolution of wireless communications require a wide variety of baseband implementations within a short time-to-market. Besides, the exponentially increased design complexity and design cost of deep sub-micron silicon highly desire the designs to be reused as much as possible. This yields an increasing demand for reconfigurable/ programmable baseband solutions. Implementing all baseband functionalities on programmable architectures, as foreseen in the tier-2 SDR, will become necessary in the future. However, the energy efficiency of SDR baseband platforms is a major concern. This brings a challenging gap that is continuously broadened by the exploding baseband complexity. We advocate a system level approach to bridge the gap. Specifically, we fully leverage the advantages (programmability) of SDR platforms to compensate its disadvantages (energy efficiency). Highly flexible and dynamic baseband signal processing algorithms are designed and implemented to exploit the abundant dynamics in the environment and the user requirement. Instead of always performing the best effort, the baseband can dynamically and autonomously adjust its work load to optimize the average energy consumption. In this paper, we will introduce such baseband signal processing techniques optimized for SDR implementations. The methodology and design steps will be presented together with 3 representative case studies in HSDPA, WiMAX and 3GPP LTE.     

High‐dose cefazolin on consecutive hemodialysis in anuric patients with Staphylococcal bacteremia

Methicillin‐sensitive Staphylococcus aureus (MSSA) bacteremia is a leading cause of infection in hemodialysis (HD) patients. Cloxacillin, cefazolin, and vancomycin are the mainstay antimicrobials. Cloxacillin administration leads to frequent drug dosing, longer length of stay (LOS), and higher cost, while resistance and poorer outcomes are associated with vancomycin use. Dosing cefazolin during HD allows for prolonged blood therapeutic levels. We assessed the outcomes and safety of a strategy of treating MSSA bacteremia with 2–3 g cefazolin on HD only. All HD patients with MSSA bacteremia admitted in June–December 2009 at our center and receiving this regime were compared with historical controls who received cloxacillin. Demographic characteristics and outcome measures like mortality, LOS, cost, recrudescence, and adverse drug reactions were assessed. Of 27 consecutive episodes reviewed, 14 and 13 patients received cefazolin and cloxacillin, respectively. Baseline demographics were comparable between the 2 treatment groups. More than one‐third of the bacteremia was related to tunneled catheter infection. The 30‐day mortality of cloxacillin‐ and cefazolin‐treated patients was 15% and 7%, respectively (P=0.14). Two of the 11 survivors treated with cloxacillin (18%) had recrudescent bacteremia while none was observed in cefazolin‐treated survivors. Cefazolin was associated with shorter LOS (10 vs. 20 days, P<0.05) and lower cost (US$8262.00 vs. US$15,367.00, P<0.05). Cefazolin use resulted in 3 idiosyncratic adverse drug reactions. Cefazolin dosed on each HD in MSSA bacteremia leads to earlier discharge and less cost. Larger prospective studies are, however, warranted to fully assess its safety and efficacy.     

Using Superconducting Magnet to Reproduce Quick Variations of Gravity in Liquid Oxygen

A ground based facility (OLGA), providing magnetic compensation of gravity in oxygen, has been developed. A 2-T superconducting magnetic solenoid is used to create the required magnetic field. A novel electrical supply permits to quickly vary the magnetic field, leading to rapid variation of the acceleration forces applied to oxygen. These variations can be made from overcompensation of gravity (−0.5g) to zero gravity or from zero gravity to reduced gravity (0.4g) with a time constant of 340 ms. This time is typical of the cutoff or reignition of spacecraft engines. Preliminary results on the transient flows induced by these acceleration variations in a reservoir filled with liquid and gaseous oxygen are presented.     

Geometrical analysis of thread milling—part 2: calculation of uncut chip thickness

Thread milling offers interesting possibilities for machining internal or external threads. This machining technique uses a mill with a triangular profile for metric threads and a helical interpolation strategy. Thus, the uncut chip thickness cannot be easily evaluated from a simplified approach. The present study deals with a model for calculating uncut chip thickness during internal thread milling. This step is needed to understand and model the cutting forces. The model developed uses the geometrical definitions of the mill and takes into account the milling mode and the cutting conditions. The link with the interferences between the tool and the thread is also established and corroborates a previous study. A full analytical formulation of the problem is proposed, and results from different milling settings are presented.     

Physical aging in polymers: Comparison of two ways of determining narayanaswamy's parameter

In this work, we have investigated by differential scanning calorimetry the enthalpy relaxation of two poly[methyl(α-n-alkyl)acrylates] in which it is possible to change the length of the two alkyl chains. In particular, we have evaluated the Narayanaswamy parameter, which controls relative contribution of temperature and of structure to the relaxation times, by two methods: Grenet's method (GM) and the peak-shift method (PSM). The data obtained show that both methods lead to equivalent results. Nevertheless, PSM requires fewer experiments than GM, and PSM appears to be more practical. The results obtained on the two acrylates show that the parameter x increases with the lateral chain length, that is to say, that the temperature effects increase as the length of the alkyl chain is increased.