A quantitative indicator diagram for lytic polysaccharide monooxygenases reveals the role of aromatic surface residues in HjLPMO9A regioselectivity

Lytic polysaccharide monooxygenases ( LPMOs) have changed our understanding of lignocellulosic degradation dramatically over the last years. These metalloproteins catalyze oxidative cleavage of recalcitrant polysaccharides and can act on the C1 and/or C4 position of glycosidic bonds. Structural data have led to several hypotheses, but we are still a long way from reaching complete understanding of the factors that determine their divergent regioselectivity. Site-directed mutagenesis enables the investigation of structure-function relationship in enzymes and will be of major importance in unraveling this intriguing matter. In this context, it is crucial to have an enzyme assay or screening approach with a direct correlation with the desired functionality. LPMOs render this search extra challenging due to their insoluble substrates, complex pattern of reaction products and lack of synthetic standards of most oxidized products. Here, we describe a regioselectivity indicator diagram based on the time-course of only 2 HPAEC-PAD signals. The diagram was successfully used to confirm the hypothesis that aromatic surface residues influence the C1/C4 oxidation ratio in Hypocrea jecorina LPMO9A. Consequently, the diagram should become a valuable tool in the search towards better understanding and engineering of regioselectivity in LPMOs

Setting reference level in the human safety guidelines via nerve activation intercomparison at IF

International guidelines/standards have been published for human protection from electromagnetic field exposure. The research in the intermediate frequencies (IF: 300 Hz-10 MHz) is scattered unlike for other frequencies, and thus the limit prescribed in the guidelines/standards are different by a factor of 10. The IEEE International Committee on Electromagnetic Safety has published a research agenda for exploring the electrostimulation thresholds. However, the consistency of the excitation models for specific target tissue needs to be revised. For this purpose, we present the first intercomparison study using multiphysics modelling to investigate stimulation thresholds during transcranial magnetic stimulation (TMS). To define the stimulation threshold, a noninvasive technique for brain stimulation has been used. In this study, by incorporating individual neurons into electromagnetic computation in realistic head models, stimulation thresholds can be determined. The study case of one subject showed that the allowable external magnetic field strength in the current guidelines/standard is conservative

Exposure and neuronal excitation by wireless power transfer for auricular vagus nerve stimulation

Inductive wireless power transfer (WPT) can be used to power implanted as well as wearable medical devices, such as a percutaneous auricular vagus nerve stimulation device. This device is placed on the neck of the patient and is connected to needle electrodes in the auricle. With regard to WPT, limitations on exposure to electric and magnetic fields should not be exceeded. Furthermore, these fields should not interfere with the therapeutic goal of stimulation, i.e., with unintended peripheral nerve stimulation in the auricle. These effects are investigated by numerical simulation of induced internal fields in the head and neck and, for the first time, subsequent neuronal simulations, quantifying the potential of neuronal excitation by the fields in the auricle in particular. Internal electric field values were in the range of 1\%-5\% of the ICNIRP 2010 basic restrictions, and current densities were in the range of 30\%-45\% of the ICNIRP 1998 basic restrictions, indicating that all tested configurations are conform the guidelines. Basic restrictions on heating of tissue turned out not to be of relevance for this application. Thresholds for neuronal stimulation were two orders of magnitude higher than the induced fields, suggesting that there is almost no risk for unintended stimulation

Surrogate modeling based cognitive decision engine for optimization of WLAN performance

Due to the rapid growth of wireless networks and the dearth of the electromagnetic spectrum, more interference is imposed to the wireless terminals which constrains their performance. In order to mitigate such performance degradation, this paper proposes a novel experimentally verified surrogate model based cognitive decision engine which aims at performance optimization of IEEE 802.11 links. The surrogate model takes the current state and configuration of the network as input and makes a prediction of the QoS parameter that would assist the decision engine to steer the network towards the optimal configuration. The decision engine was applied in two realistic interference scenarios where in both cases, utilization of the cognitive decision engine significantly outperformed the case where the decision engine was not deployed

Assessment of nerve cathodal block for the percutaneous auricular vagus nerve stimulation

Nerve cathodal block mechanism for the percutaneous auricular vagus nerve stimulation is investigated. The response of individual axons to stimulation will be assessed in terms of excitation, blocking and propagation of action potentials in order to optimize stimulation patterns. It was seen that the response obeyed the activating function remarkably well. The found sensitivity indices of the blocking threshold for variations in diameter and temperature (61 % and 15 % respectively) are significantly higher than for the excitation threshold. Finally, the threshold needed for cathodal block (around -5 V) is far from the amplitudes used to stimulate the nerves (around -1 V). More investigations by performing an uncertainty analysis varying axonal trajectories and electrode placement can lead to the conclusion that cathodal block is less likely to occur when stimulating with clinically used amplitudes in pVNS

Linking users' subjective QoE evaluation to signal strength in an IEEE 802.11b/g wireless LAN environment

Although the literature on Quality of Experience (QoE) has boomed over the last few years, only a limited number of studies have focused on the relation between objective technical parameters and subjective user-centric indicators of QoE. Building on an overview of the related literature, this paper introduces the use of a software monitoring tool as part of an interdisciplinary approach to QoE measurement. In the presented study, a panel of test users evaluated a mobile web-browsing application (i.e., Wapedia) on a PDA in an IEEE 802.11b/g Wireless LAN environment by rating a number of key QoE dimensions on the device immediately after usage. This subjective evaluation was linked to the signal strength, monitored during PDA usage at four different locations in the test environment. The aim of this study is to assess and model the relation between the subjective evaluation of QoE and the (objective) signal strength in order to achieve future QoE optimization

Sensitivity study of neuronal excitation and cathodal blocking thresholds of myelinated axons for percutaneous auricular vagus nerve stimulation

Objective: Excitation of myelinated nerve fibers is investigated by means of numerical simulations, for the application of percutaneous auricular vagus nerve stimulation (pVNS). High sensitivity to axon diameter is of interest regarding the goal of targeting thicker fibers. Methods: Excitation and blocking thresholds for different pulse types, phase durations, axon depths, axon-electrode distances, temperatures and axon diameters are investigated. The used model consists of a 50 mm long axon and a centrally located needle electrode in a layered medium representing the auricle. Neuronal excitation is simulated using the Frankenhaeuser-Huxley equations for all combinations of parameter values. Results and conclusion: Multiple modes and locations of excitation along the axon were observed, depending on the pulse type and amplitude. When increasing the axon-electrode distance from 1 mm to 2 mm, sensitivity of thresholds to axon depth decreased with ca. 50%, while sensitivity to axon-electrode distance, axon diameter and phase duration each increased with ca. 15% to 20%, except from monophasic anodal pulses, showing a 45% decrease for axon-electrode distance. These trends for axon diameter and axon-electrode distance allow for more selective stimulation of thicker target fibers using monophasic anodal pulses at higher axon-electrode distances. Cathodal monophasic pulses did not perform well due to blocking of the thicker fibers, which was only rarely seen for other pulse types. Significance: Sensitivities of stimulation thresholds to these parameters by numerical simulation reveal how the stimulation parameters can be changed in order to increase therapeutic effect and comfort during pVNS by enabling more selective stimulation

Brain cortical stimulation thresholds to different magnetic field sources exposures at intermediate frequencies

Permissible field strengths in the international guidelines/standard for human protection are derived from peripheral nerve system stimulation at the intermediate frequencies where electrostimulation (attributable to axon activation) is more dominant than thermal effect. Recently, multiscale computation has been used to investigate neuron stimulation thresholds by incorporating individual neurons into realistic head models. However, the consistency of excitation models and permissible levels to specific target tissues (central nervous system) needs to be clarified. This article aims to investigate brain cortical stimulation thresholds using a multiscale computational approach for different scenarios of magnetic field exposures. The magnetic exposures include transcranial magnetic stimulation, uniform exposure, and wireless power transfer systems. Our results confirmed the consistency of the multiscale computations of the cortical thresholds between two independent groups for electromagnetic exposure of transcranial magnetic stimulation (thresholds in the range of motor cortex activation). We also quantified the conservativeness of permissible field strengths of international guidelines/standards at intermediate frequencies. Finally, with the multiscale approach, we confirmed that 10 000 kW of transmitting power of wireless power transfer (WPT) in an electric vehicle charging system may not induce an adverse effect for cortical activation

A cognitive QoS management framework for WLANs

Due to the precipitous growth of wireless networks and the paucity of spectrum, more interference is imposed to the wireless terminals which constraints their performance. In order to preserve such performance degradation, this paper proposes a framework which uses cognitive radio techniques for quality of service (QoS) management of wireless local area networks (LANs). The framework incorporates radio environment maps as input to a cognitive decision engine that steers the network to optimize its QoS parameters such as throughput. A novel experimentally verified heuristic physical model is developed to predict and optimize the throughput of wireless terminals. The framework was applied to realistic stationary and time-variant interference scenarios where an average throughput gain of 344% was achieved in the stationary interference scenario and 70% to 183% was gained in the time-variant interference scenario

T-cell and serological responses to Erp, an exported Mycobacterium tuberculosis protein, in tuberculosis patients and healthy individuals

<p>Abstract</p> <p>Background</p> <p>The identification of antigens able to differentiate tuberculosis (TB) disease from TB infection would be valuable. Cellular and humoral immune responses to Erp (Exported repetitive protein) – a recently identified <it>M. tuberculosis </it>protein – have not yet been investigated in humans and may contribute to this aim.</p> <p>Methods</p> <p>We analyzed the cellular and humoral immune responses to Erp, ESAT-6, Ag85B and PPD in TB patients, in BCG⁺individuals without infection, BCG⁺individuals with latent TB infection (LTBI) and BCG^-controls. We used lymphoproliferation, ELISpot IFN-γ, cytokine production assays and detection of specific human antibodies against recombinant <it>M. tuberculosis </it>proteins.</p> <p>Results</p> <p>We included 22 TB patients, 9 BCG⁺individuals without TB infection, 7 LTBI and 7 BCG^-controls. Erp-specific T cell counts were higher in LTBI than in the other groups. Erp-specific T cell counts were higher in LTBI subjects than TB patients (median positive frequency of 211 SFC/10⁶PBMC (range 118–2000) for LTBI subjects compared to 80 SFC/10⁶PBMC (range 50–191), p = 0.019); responses to PPD and ESAT-6 antigens did not differ between these groups. IFN-γ secretion after Erp stimulation differed between TB patients and LTBI subjects (p = 0.02). Moreover, LTBI subjects but not TB patients or healthy subjects produced IgG3 against Erp.</p> <p>Conclusion</p> <p>The frequencies of IFN-γ-producing specific T cells, the IFN-γ secretion and the production of IgG3 after Erp stimulation are higher in LTBI subjects than in TB patients, whereas PPD and ESAT-6 are not.</p