Screening of a Drug Library Identifies Inhibitors of Cell Intoxication by CNF1

Cytotoxic necrotizing factor 1 (CNF1) is a toxin produced by pathogenic strains of Escherichia coli responsible for extra‐intestinal infections. CNF1 deamidates Rac1, thereby triggering its permanent activation and worsening inflammatory reactions. Activated Rac1 is prone to proteasomal degradation. There is no targeted therapy against CNF1, despite its clinical relevance. In this work we developed a fluorescent cell‐based immunoassay to screen for inhibitors of CNF1‐induced Rac1 degradation among 1120 mostly approved drugs. Eleven compounds were found to prevent CNF1‐induced Rac1 degradation, and five also showed a protective effect against CNF1‐induced multinucleation. Finally, lasalocid, monensin, bepridil, and amodiaquine protected cells from both diphtheria toxin and CNF1 challenges. These data highlight the potential for drug repurposing to fight several bacterial infections and Rac1‐based diseases.     

Transonic,thermodilution, or ionic dialysance to manage vascular access: Which method is best?

Regularly monitoring blood flow through a vascular access (Qa) can predict a dysfunction and dramatically reduce the number of thromboses. The aim of our study was to compare two integrated access flow devices, thermodilution (Qa‐BTM: BTM®, Fresenius Medical Care, Bad Homburg, Germany) and ionic dialysance (Qa‐ID: OCM®, Fresenius Medical Care, Bad Homburg, Germany), with the “gold standard” saline dilution (Qa‐T: Transonic®, Systems Inc., Ithaca, NY, USA). Measurements were performed sequentially and were repeated in the first 90 minutes of a single dialysis session in 24 long‐term hemodialysis patients with a vascular access. Bland–Altman, linear regression (r²), and intraclass correlation coefficients (ICC) assessed reproducibility, correlations, and concordance between the techniques. Average access flow for Qa‐T was 1549 (± 844) mL/minute, Qa‐BTM was 1530 (± 856) mL/minute (P = NS), and Qa‐ID was 1619 (± 1085) mL/minute (P = NS). Respectively, ICC, (r²), and bias were 0.99, (0.98), and ?19 mL/minute for Qa‐BTM, and 0.75, (0.65), and +69 mL/minute for Qa‐ID. The limits of agreement were ?287 to +250 mL/minute for Qa‐BTM and ?1647 to +1785 mL/minute for Qa‐ID. Reproducibility of thermodilution and ionic dialysance, expressed as relative differences, was not significantly different from saline dilution. Recirculation, measured by saline dilution, was 0% (0–4%), the same as the 0% measured by thermodilution, with correct placement of bloodlines and corrected for cardiopulmonary recirculation. The integrated access flow measurement devices, thermodilution and ionic dialysance, are reasonable alternatives to using saline dilution to measure Qa: Thermodilution showed better precision and correlation. They are reliable, make monitoring of vascular access easier, incur no extra costs, and use no additional consumables.     

Analytical Analysis of Applying Packet Fragmentation Mechanism on Both Basic and RTS/CTS Access Methods of the IEEE 802.11b DCF Network Under Imperfect Channel and Finite Load Conditions

The mathematical modeling and performance evaluation of the IEEE 802.11 network in all its various extensions (802.11b, 802.11a, 802.11g, 802.11e, 802.11n, etc.) have already been widely explored over the past years. However, the Packet Fragmentation Mechanism (PFM), which is proposed by the IEEE work group to enhance the MAC sub-layer of the IEEE 802.11 standard in an error-prone channel, has been missed in the available literature. Yet, the PFM is the only existing solution to reduce the influence of bit error rate and the length of data packets on the packet error rate, and consequently on the performances of IEEE 802.11 networks. In this paper, we propose a new three-dimensional Markov chain in order to model, for the first time in the literature, the PFM in both Basic and RTS/CTS access methods of the IEEE 802.11b DCF network under imperfect channel and finite load conditions. Then, we develop mathematical models to derive a variety of performance metrics, such as: the overall throughput, the average packet delay successfully transmitted, the average packet drop time, the delay jitter and the packet delay distribution. Performance analysis of applying PFM on both Basic and RTS/CTS access methods of the IEEE 802.11b DCF network under imperfect channel and finite load conditions shows original results and leads to new conclusions that could not be intuitively expected.     

Case Study: Color Control in the Automotive Industry

Numerous manufacturers are concerned with ensuring the homogeneity in the colors of different parts that compose their products. This quality objective of primary importance is especially challenging when the parts are sourced by different suppliers. The technical difficulties are accentuated when metallic or pearly paints are used since the presence of metallic chips in the paint causes a variation in the color according to the angle of observation. Also, the development of metametric colors increases these difficulties even more, as these colors are sensitive to different illumination sources. The present study relates to the production of colored car bumpers. By using a spectrocolorimeter and color samples, the process is improved to better respect the customer specifications. To achieve this, critical colors and significant parameters affecting colors are identified, design of experiments is used to optimize the process settings, and a correlation study allows further process improvement. The results achieved are impressive: the quality index used has been improved by 67% in only 6 months. This case study therefore illustrates how simple quality tools can be used in a rigorous search for process improvement toward total color mastering with zero defect objective.     

The role of international agencies, governments, and the private sector in the diffusion of modern contraception

This paper views diffusion as encompassing three processes: the acceptance of the idea and practice of contraception by consumers; the establishment of the institutions or programs to provide services; and the development of technical capability in research and development and in the production of contraceptives. The historical development of the family planning movement is described, and the contribution of international agencies, governments, and private sectors is discussed in the context of changing development approaches. Substantial achievements have been made, but, in view of future needs and the uncertainty of political and financial commitment to family planning on the part of donors, the future presents a continuing challenge.     

MRx design and criticism: the confluence of media studies,performance and social interaction

Abstract

In this article, we bring together the lenses of media studies, performance studies and social interaction offered in the other essays in this special issue and discuss their collective contribution towards a more nuanced understanding of MR^x. We illustrate this capacity by a brief critical review of a recent MR^x environment: Mégaphone. We suggest how the lenses can also contribute to a design vocabulary for future MR^x experiences.     

CONTRIBUTION TO HEAT TRANSFER IN AIR-LIFT AND BUBBLE COLUMN FERMENTORS WITH NEWTONIAN AND NON-NEWTONIAN SOLUTIONS

Heat transfer in five air-lift and bubble column bioreactors has been investigated. Water (Newtonian) and xanthan solutions (non-Newtonian) were used. The effects of superficial gas velocity, liquid-phase viscosity and riser-to-downcomer cross-section area ratio have been studied. In air-lift slightly higher heat transfer coefficients were observed than in bubble column reactors. The superficial gas velocity and the effective liquid-phase viscosity influence strongly the heat transfer performance in all systems studied. Following the surface renewal concept, general correlations for heat transfer in Newtonian and non-Newtonian fermentation broth were developed. They describe precisely heat transfer coefficients in a wide range of operating and geometrical conditions.     

Combination of model-based observer and support vector machines for fault detection of wind turbines

Support vector machines and a Kalman-like observer are used for fault detection and isolation in a variable speed horizontalaxis wind turbine composed of three blades and a full converter. The support vector approach is data-based and is therefore robust to process knowledge. It is based on structural risk minimization which enhances generalization even with small training data set and it allows for process nonlinearity by using flexible kernels. In this work, a radial basis function is used as the kernel. Different parts of the process are investigated including actuators and sensors faults. With duplicated sensors, sensor faults in blade pitch positions,generator and rotor speeds can be detected. Faults of type stuck measurements can be detected in 2 sampling periods. The detection time of offset/scaled measurements depends on the severity of the fault and on the process dynamics when the fault occurs. The converter torque actuator fault can be detected within 2 sampling periods. Faults in the actuators of the pitch systems represents a higher difficulty for fault detection which is due to the fact that such faults only affect the transitory state(which is very fast) but not the final stationary state. Therefore, two methods are considered and compared for fault detection and isolation of this fault: support vector machines and a Kalman-like observer. Advantages and disadvantages of each method are discussed. On one hand, support vector machines training of transitory states would require a big amount of data in different situations, but the fault detection and isolation results are robust to variations in the input/operating point. On the other hand, the observer is model-based, and therefore does not require training, and it allows identification of the fault level, which is interesting for fault reconfiguration. But the observability of the system is ensured under specific conditions, related to the dynamics of the inputs and outputs. The whole fault detection and isolation scheme is evaluated using a wind     

Flow characterization in T-shaped and cross-shaped micromixers

The understanding of physical phenomena such as flow behaviour and mass transfer performance is needed in order to develop appropriate micromixers for industrial or biomedical applications. In this article, the flow behaviour of the T-shaped and the cross-shaped micromixers with square cross-section are studied through numerical and experimental investigations. The comparisons are based on identical treated fluxes. From the particle image velocimetry (PIV) measurements, the flow topologies in the T-shaped and cross-shaped micromixers are very different. After liquid impact, it is observed that the vortex structures cover a longer part of the outlet channel in the case of the cross geometry. This result indicates that the cross-shaped micromixer could improve the mixing process in comparison with the micromixers having T geometry. A second experimental technique has been used, the electrochemical one, involving microelectrodes placed at several wall positions of the cross-shaped micromixer. The electrochemical method can locally characterize the formation of swirling flows. The high values of wall shear rate, in the impact zone, confirm the near wall disturbance created by the impingement of the flow and also the appearance of vortices that could enhance fluid mixing.