In vitro efficacy of artemisinin-based treatments against SARS-CoV-2

Effective and affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are needed. We report in vitro efficacy of Artemisia annua extracts as well as artemisinin, artesunate, and artemether against SARS-CoV-2. The latter two are approved active pharmaceutical ingredients of anti-malarial drugs. Concentration–response antiviral treatment assays, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that treatment with all studied extracts and compounds inhibited SARS-CoV-2 infection of VeroE6 cells, human hepatoma Huh7.5 cells and human lung cancer A549-hACE2 cells, without obvious influence of the cell type on antiviral efficacy. In treatment assays, artesunate proved most potent (range of 50% effective concentrations (EC50) in different cell types: 7–12 µg/mL), followed by artemether (53–98 µg/mL), A. annua extracts (83–260 µg/mL) and artemisinin (151 to at least 208 µg/mL). The selectivity indices (SI), calculated based on treatment and cell viability assays, were mostly below 10 (range 2 to 54), suggesting a small therapeutic window. Time-of-addition experiments in A549-hACE2 cells revealed that artesunate targeted SARS-CoV-2 at the post-entry level. Peak plasma concentrations of artesunate exceeding EC50 values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment

The problem of a metal impurity in an oxide: ab-initio study of electronic and structural properties of Cd in Rutile TiO2

In this work we undertake the problem of a transition metal impurity in an oxide. We present an ab-initio study of the relaxations introduced in TiO2 when a Cd impurity replaces substitutionally a Ti atom. Using the Full-Potential Linearized-Augmented-Plane-Wave method we obtain relaxed structures for different charge states of the impurity and computed the electric-field gradients (EFGs) at the Cd site. We find that EFGs, and also relaxations, are dependent on the charge state of the impurity. This dependence is very remarkable in the case of the EFG and is explained analyzing the electronic structure of the studied system. We predict fairly anisotropic relaxations for the nearest oxygen neighbors of the Cd impurity. The experimental confirmation of this prediction and a brief report of these calculations have recently been presented [P.R.L. 89, 55503 (2002)]. Our results for relaxations and EFGs are in clear contradiction with previous studies of this system that assumed isotropic relaxations and point out that no simple model is viable to describe relaxations and the EFG at Cd in TiO2 even approximately.Comment: 11 pages, 8 figures, Revtex 4, published in Physical Review

Mental fatigue after very severe closed head injury: Sustained performance, mental effort, and distress at two levels of work-load in a driving simulator

In patients with very severe closed head injury (CHI), returning to work is often problematic. The present study focuses on a persistent complaint of these patients, viz. mental fatigue. To study this, the effect of sustained workload is assessed in a continuous dynamic divided attention task. Three types of measures are employed: performance loss with time-on-task, and subjective reports and cardiovascular measures of mental effort and distress. Eight very severe CHI patients (mean post-traumatic amnesia duration 51 days, mean age 23 years, (SD 6.4) and eight hospital controls (mean age 29 years, (SD 5.9) were tested. No differences were found between the patients and controls in the effects of task load on performance and the amount of mental effort, even in very demanding simulated work conditions. This parallels previous findings in less demanding laboratory tasks of sustained attention. Effects of CHI were found on both subjective and physiological indicators of distress. Compared to the controls, patients showed stronger effects on systolic blood pressure and subjectively experienced load

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

High-Voltage Actuation System for Future Generation Lithography systems - Power Amplifier

Current motion systems in lithography machines operate at a bus voltage of 600V after a steady increase in the past decades. Increasing the voltage has the advantage of delivering more power without the cost of an increase in mass and volume of power cables. However, this requires a significant breakthrough in power amplifier technology since fast switching MOSFETs can only be used reliably up to 600 V and for higher voltages only slower switching devices are available

Hybrid multilevel converter based on flying capacitor and extended commutation cell

The extended commutation cell (ECC) is a promising\u3cbr/\u3eswitching cell that allows for bidirectional energy transport in\u3cbr/\u3etwo orthogonal directions throughout the cell. By combining the\u3cbr/\u3eECC with a flying capacitor (FC) converter topology, a multilevel converter with a high number of levels can be assembled. This paper presents the analysis of a hybrid converter composed of an arbitrary number of ECCs and a flying capacitor. A 3 kW inverter configuration consisting of two ECCs and a flying capacitor is designed and verified by simulation. The result is a 12-level hybrid converter with equidistant output levels and closed loop control of the capacitor voltages of the ECC and FC. The required number of switches decreases from 22 in a 12-level FC converter to 12 in the proposed hybrid configuration, with the addition of two inductors

Hybrid multilevel converter based on flying capacitor and extended commutation cell

A recently introduced multilevel multicell concept is the extended\u3cbr/\u3ecommutation cell (ECC). The ECC is an advanced power electronics\u3cbr/\u3eswitching structure that allows for more flexibility in power\u3cbr/\u3econverter design. Adding multiple cells in series results in a rapid\u3cbr/\u3e(exponential) increase in the number of levels. Combining multiple\u3cbr/\u3eECCs with a flying capacitor (FC) cell results in a relatively large\u3cbr/\u3enumber of output levels with relatively low control effort and low\u3cbr/\u3enumber of components

High-voltage actuation system for future generation lithography systems: power amplifier

Current motion systems in lithography machines operate at a bus voltage of 600 V after a steady increase in the past decades. Increasing the voltage has the advantage of delivering more power without the cost of an increase in mass and volume of power cables. However, this requires a significant breakthrough in power amplifier technology since fast switching MOSFETs can only be used reliably up to 600 V and for higher voltages only slower switching devices are available. Fast switching SiC MOSFETs with higher forward voltages are available but are not sufficient for the required voltage increase

Flying capacitor resonant pole inverter applying five voltage levels

Fast-moving high precision stages in lithographic equipment require power amplifiers with high output power and high precision output current generation capabilities. In the past, the increasing demand for more output power has been fulfilled mostly by increasing output current, which increases the thermal load on amplifiers, interconnections and actuators. In order to increase the output power when the available rms current is limited, the operating voltage of the system needs to be increased. This imposes a new set of challenges for the power amplifier, as reliable fast switching devices are not available with high blocking voltages

High-Voltage Actuation System for Future Generation Lithography systems - Power Amplifier

Current motion systems in lithography machines operate at a bus voltage of 600V after a steady increase in the past decades. Increasing the voltage has the advantage of delivering more power without the cost of an increase in mass and volume of power cables.\u3cbr/\u3eHowever, this requires a significant breakthrough in power amplifier technology since fast switching MOSFETs can only be used reliably up to 600 V and for higher voltages only slower switching devices are available