CYP154C5 Regioselectivity in Steroid Hydroxylation Explored by Substrate Modifications and Protein Engineering**

CYP154C5 from Nocardia farcinica is a P450 monooxygenase able to hydroxylate a range of steroids with high regio- and stereoselectivity at the 16α-position. Using protein engineering and substrate modifications based on the crystal structure of CYP154C5, an altered regioselectivity of the enzyme in steroid hydroxylation had been achieved. Thus, conversion of progesterone by mutant CYP154C5 F92A resulted in formation of the corresponding 21-hydroxylated product 11-deoxycorticosterone in addition to 16α-hydroxylation. Using MD simulation, this altered regioselectivity appeared to result from an alternative binding mode of the steroid in the active site of mutant F92A. MD simulation further suggested that the entrance of water to the active site caused higher uncoupling in this mutant. Moreover, exclusive 15α-hydroxylation was observed for wild-type CYP154C5 in the conversion of 5α-androstan-3-one, lacking an oxy-functional group at C17. Overall, our data give valuable insight into the structure–function relationship of this cytochrome P450 monooxygenase for steroid hydroxylation.     

Airwriting: a wearable handwriting recognition system

We present a wearable input system which enables interaction through 3D handwriting recognition. Users can write text in the air as if they were using an imaginary blackboard. The handwriting gestures are captured wirelessly by motion sensors applying accelerometers and gyroscopes which are attached to the back of the hand. We propose a two-stage approach for spotting and recognition of handwriting gestures. The spotting stage uses a support vector machine to identify those data segments which contain handwriting. The recognition stage uses hidden Markov models (HMMs) to generate a text representation from the motion sensor data. Individual characters are modeled by HMMs and concatenated to word models. Our system can continuously recognize arbitrary sentences, based on a freely definable vocabulary. A statistical language model is used to enhance recognition performance and to restrict the search space. We show that continuous gesture recognition with inertial sensors is feasible for gesture vocabularies that are several orders of magnitude larger than traditional vocabularies for known systems. In a first experiment, we evaluate the spotting algorithm on a realistic data set including everyday activities. In a second experiment, we report the results from a nine-user experiment on handwritten sentence recognition. Finally, we evaluate the end-to-end system on a small but realistic data set.     

Output feedback control for uncertain linear systems with faulty actuators based on a switching method

This paper investigates the problem of output feedback stabilization for a class of uncertain linear systems with faulty actuators via the synergy with a switching strategy. When actuators suffer a ‘destabilizing failure’ and the never‐faulty actuators cannot stabilize the given system, the closed‐loop exponential stability can still be achieved via the average dwell‐time scheme employing an arbitrary switching signal. The prerequisite condition found requires the ratio between the two lapse times, when the system is devoid of faulty actuators and when it is not so, to be less than a certain specified constant. Then the stabilizing output feedback controls are designed via the technique of linear matrix inequalities. The illustrative example and the respective simulation results demonstrate the feasibility and effectiveness of the proposed design synthesis. Copyright © 2008 John Wiley & Sons, Ltd.     

Tracking control for switched linear systems with time‐delay: a state‐dependent switching method

Tracking control for switched linear systems with time‐delay is investigated in this paper. Based on the state‐dependent switching method, sufficient conditions for the solvability of the tracking control problem are given. We use single Lyapunov function technique and a typical hysteresis switching law to design a tracking control law such that the H_∞ model reference tracking performance is satisfied. The controller design problem can be solved efficiently by using linear matrices inequalities. Since convex combination techniques are used to derive the delay independent criteria, some subsystems are allowed to be unstable. It is highly desirable that a non‐switched time‐delay system can not earn such property. Simulation example shows the feasibility and validity of the switching control law. Copyright © 2009 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society     

Decentralized adaptive synchronization of an uncertain complex delayed dynamical network

In this paper, we investigate the locally and globally adaptive synchronization problem for an uncertain complex dynamical network with time-varying coupling delays based on the decentralized control. The coupling terms here are bounded by high-order polynomials with known gains that are ubiquitous in a large class of complex dynamical networks. We generalize the usual technology of searching for an appropriate coordinates transformation to change the network dynamics into a series of decoupled lower-dimensional systems. Several adaptive synchronization criteria are derived by constructing the Lyapunov-Krasovskii functional and Barbalat lemma, and the proposed criteria are simple in form and convenient for the practical engineering design. Numerical simulations illustrated by a nearest-neighbor coupling network verify the effectiveness of the proposed synchronization scheme.     

Feedback passivation of switched nonlinear systems using storage-like functions

This paper addresses the issues of passivity and feedback passivation of switched nonlinear systems via multiple storage functions. The concept of storage-like functions for switched systems is presented. A sufficient condition for passivity of switched nonlinear systems is given via multiple storage functions under some switching signal. Then, the result is extended to find conditions under which a switched system is feedback equivalent to a passive switched system. Furthermore, passivity of switched cascade systems is investigated.     

A formulation for near-wall RANS/LES coupling

A near-wall eddy-viscosity formulation for LES is presented. A RANS-like eddy-viscosity corrected with the resolved turbulent stress is imposed in the near-wall region. The RANS eddy-viscosity is obtained from a resolved LES of channel flow at Re_τ = 395 and stored in a look-up table. When used with a wall stress model, this technique enables LES to be performed on coarse grids. Results are presented for channel flow at several Reynolds numbers up to Re_τ = 10,000. Various issues concerning the numerical behavior of the method are discussed.     

The impact of the composition of structural steels on their corrosion stability in liquid Pb-Bi at 500 and 400 °C with different oxygen concentrations

In recent years, heavy liquid metals have found exercise as possible coolants and targets in the conversion of radioactive elements in accelerator driven systems (ADS). Liquid lead-bismuth eutectic alloy is one of candidates for this using tanks to its suitable nuclear and physical properties. Performed examination was aimed at research of compatibility choice materials for parts of ADS with liquid Pb-Bi eutectic alloy, influence of composition choice materials on their corrosion resistance, influence of temperature and oxygen content. We performed corrosion tests of 1000 h each on approximately 20 types of structural steels (austenitic, ferritic and martensitic) in convection loops with flowing Pb-Bi at 500 and 400 °C and using different oxygen concentrations. The impact of Fe, Cr, Ni, Mn, Si, Al and Mo content on the corrosion stability of these steels was measured without and after preliminary passivation through creating thin spinel or oxide layers on their surface.     

Myo-Inositol Limits Kainic Acid-Induced Epileptogenesis in Rats

Epilepsy is a severe neurological disease characterized by spontaneous recurrent seizures (SRS). A complex pathophysiological process referred to as epileptogenesis transforms a normal brain into an epileptic one. Prevention of epileptogenesis is a subject of intensive research. Currently, there are no clinically approved drugs that can act as preventive medication. Our previous studies have revealed highly promising antiepileptogenic properties of a compound–myo-inositol (MI) and the present research broadens previous results and demonstrates the long-term disease-modifying effect of this drug, as well as the amelioration of cognitive comorbidities. For the first time, we show that long-term treatment with MI: (i) decreases the frequency and duration of electrographic SRS in the hippocampus; (ii) has an ameliorating effect on spatial learning and memory deficit associated with epileptogenesis, and (iii) attenuates cell loss in the hippocampus. MI treatment also alters the expression of the glial fibrillary acidic protein, LRRC8A subunit of volume-regulated anion channels, and protein tyrosine phosphatase receptor type R, all expected to counteract the epileptogenesis. All these effects are still present even 4 weeks after MI treatment ceased. This suggests that MI may exert multiple actions on various epileptogenesis-associated changes in the brain and, therefore, could be considered as a candidate target for prevention of epileptogenesis.     

Syndecan-4 Is a Key Facilitator of the SARS-CoV-2 Delta Variant’s Superior Transmission

Emerging SARS-CoV-2 variants pose threats to vaccination campaigns against COVID-19. Being more transmissible than the original virus, the SARS-CoV-2 B.1.617 lineage, named the Delta variant, swept through the world in 2021. The mutations in the Delta’s spike protein shift the protein towards a net positive electrostatic potential. To understand the key molecular drivers of the Delta infection, we investigate the cellular uptake of the Delta spike protein and Delta spike-bearing SARS-CoV-2 pseudoviruses. Specific in vitro modification of ACE2 and syndecan expression enabled us to demonstrate that syndecan-4, the syndecan isoform abundant in the lung, enhances the transmission of the Delta variant by attaching its mutated spike glycoprotein and facilitating its cellular entry. Compared to the wild-type spike, the Delta one shows a higher affinity towards heparan sulfate proteoglycans than towards ACE2. In addition to attachment to the polyanionic heparan sulfate chains, the Delta spike’s molecular interactions with syndecan-4 also involve syndecan-4’s cell-binding domain that mediates cell-to-cell adhesion. Regardless of the complexity of these interactions, exogenously added heparin blocks Delta’s cellular entry as efficiently as syndecan-4 knockdown. Therefore, a profound understanding of the molecular mechanisms underlying Delta infections enables the development of molecularly targeted yet simple strategies to reduce the Delta variant’s spread.