Functional Coupling of Slack Channels and P2X3 Receptors Contributes to Neuropathic Pain Processing

The sodium-activated potassium channel Slack (K_Na1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (I_KNa) and modulates neuronal activity. Previous studies suggest that Slack is involved in the processing of neuropathic pain. However, mechanisms underlying the regulation of Slack activity in this context are poorly understood. Using whole-cell patch-clamp recordings we found that Slack-mediated I_KNa in sensory neurons of mice is reduced after peripheral nerve injury, thereby contributing to neuropathic pain hypersensitivity. Interestingly, Slack is closely associated with ATP-sensitive P2X3 receptors in a population of sensory neurons. In vitro experiments revealed that Slack-mediated I_KNa may be bidirectionally modulated in response to P2X3 activation. Moreover, mice lacking Slack show altered nocifensive responses to P2X3 stimulation. Our study identifies P2X3/Slack signaling as a mechanism contributing to hypersensitivity after peripheral nerve injury and proposes a potential novel strategy for treatment of neuropathic pain.     

Numerical,wind-tunnel,and atmospheric evaluation of a turbulent ground-based inlet sampling system

The use of inlets for transferring aerosols from the environment to instrumentation can introduce uncertainty in the measurement of aerosol properties. Aerosol loss during this process is a non-negligible issue that may bias the subsequent measurements. These loss mechanisms include aspiration at the inlet head and deposition/evaporation/condensation during transport through the sampling lines. Coarse-mode aerosol is significantly impacted by the aspiration and inertial loss mechanisms within an inlet system. This work uses wind tunnel experiments to investigate aerosol losses through the Storm Peak Laboratory’s (SPL) new aerosol inlet system. The inlet is used extensively for both intensive field campaigns and long-term aerosol monitoring. The results of numerical simulations of the SPL aerosol inlet sampling efficiency are provided at several wind speeds, and experimental results demonstrate the system has a 50% cut off for the coarse-mode at an aerodynamic diameter of approximately 13?μm and wind speed of 0.5?m s^?1. This investigation will lead to improved accuracy of in situ aerosol measurements at SPL and this system can be replicated at other atmospheric stations.

Copyright © 2019 American Association for Aerosol Research     

A longitudinal observational study of the dynamics of Mycoplasma bovis antibodies in naturally exposed and diseased dairy cows

Mycoplasma bovis is an important pathogen causing disease and substantial economic losses in cattle. However, knowledge of the dynamics of antibody responses in individual cows in the face of an outbreak is currently extremely limited. The use of commercial antibody tests to support clinical decision-making and for surveillance purposes is therefore challenging. Our objective was to describe the dynamics of M. bovis antibody responses in 4 Danish dairy herds experiencing an acute outbreak of M. bovis-associated disease, and to compare the antibody dynamics between dairy cows with different disease manifestations. A total of 120 cows were examined using a standardized clinical protocol and categorized into 4 disease groups: “mastitis,” “systemic,” “nonspecific,” and “none.” Paired blood and milk samples were collected and tested using a commercial M. bovis antibody–detecting ELISA. Plots of raw data and generalized additive mixed models with cow and herd as random effects were used to describe serum and milk antibody dynamics relative to the estimated time of onset of clinical disease. Cows with mastitis had high optical density measurement (ODC%) of antibodies in both milk and serum at disease onset. The estimated mean ODC% in milk was below the manufacturer's cut-off for the other groups for the entire study period. The estimated mean serum ODC% in the “systemic” group was high at onset of disease and stayed above the cut-off until 65 d after disease onset. However, the lower 95% confidence interval (CI) for the mean ODC% was only above the manufacturer's cut-off between 7 and 17 d after onset of disease. The CI of the “systemic” and “none” groups did not overlap at any time between the day of disease onset and 65 d after disease onset, and the estimated mean ODC% for both the “nonspecific” and “none” groups were generally below the cut-off for the majority of the study period. In conclusion, the serum antibody responses were highly dynamic and showed a high level of variation between individual cows. This strongly suggests that serology is unlikely to be useful for individual diagnosis of M. bovis-associated disease in dairy cows. However, it might still be useful for herd- or group-level diagnosis. Antibodies in milk were only increased in cows with M. bovis mastitis, indicating that milk antibody measurements only have diagnostic utility for cows with mastitis.     

A multiple mechanism model for measuring extra- and intraparticle mass transport in ion exchange resins

A diffusion-based kinetic model for resin-based ion exchange is proposed that simultaneously describes extra- and intraparticle diffusion for the purpose of predicting batch transient adsorption rates during resin operation. The extraparticle diffusion is simulated through Newton's-law-of-cooling assuming a stagnant laminar layer, while the intraparticle simulation assumes a homogeneous internal pore environment and uses the Nernst–Planck equation to describe multi-ion diffusion. The key parameters of the model are the mass transfer coefficient, the intrinsic diffusivities of the adsorbing and desorbing ions and the equilibrium coefficient associated with the Mass-Action-Law, which is assumed to be applicable at the liquid/resin interface. A novel method is described to determine the critically important ion concentration at the interface from experiment. Kinetic tests are undertaken in a closed circuit system, adsorbing Na, Mg, and Ba ions separately onto gel type acid resin, and the simulation is fitted to the measured raw data using the Hook–Jeeves search algorithm. The intraparticle diffusivities of the three ions are hence measured and reported.     

Focussed Ion Beam

Focussed Ion Beam -“Cutting Edge” Technology of Material Analysis With the focussed ion beam technique it is possible to sputter almost any material with nanometer scale accuracy and directly image or chemically analyze structures below the surface. The major advantage towards conventional cross-section polishing is the high precision which allows to investigate even the smallest local defects. Applications of the focused ion beam even extend to the generation of complex nano structures. This article describes the operational modes, limits and constraints of the method and gives application examples from the field of material analytics.     

Characterization and variability of endotoxin and 3-hydroxy fatty acids in an office building during a particle intervention study

Air and dust samples were collected on two floors of an office building during a double-blind particle intervention study to examine spatial and temporal variability of airborne endotoxin over a period of weeks, and to characterize endotoxin activity and lipopolysaccharide (LPS) content in carpet and chair dust. Air samples were collected on multiple days within and across weeks. Dust samples were collected from carpets and chairs one day per week for three weeks. Endotoxin was measured using a Limulus assay. Dust samples were analyzed for LPS by determination of 3-hydroxy fatty acids (3-OHFAs) using gas chromatography-mass spectrometry. The geometric mean (geometric standard deviation) for 96 indoor air samples was 0.24 (1.6) EU/m3. Significant within-floor spatial variation of airborne endotoxin was found (P < 0.0001, n = 80). Temporal variability of airborne endotoxin was not significant across weeks. Mean (+/- SD) endotoxin levels in carpet dust (59 +/- 9.3 EU/mg dust, n = 12) and in chair dust (38 +/- 7.7 EU/mg dust, n = 10) were significantly different (P < 0.001). Carbon chain length-dependent differences in 3-OHFA levels by dust source and floor were found. Enhanced air filtration did not significantly affect airborne endotoxin (P = 0.62); however, total dust mass and total endotoxin in carpet dust samples increased significantly after enhanced surface cleaning (P < 0.01). These findings suggest that spatial variability, dust source, and surface cleaning may influence building occupant exposures to endotoxin.     

Capacity management under uncertainty with inter-process, intra-process and demand interdependencies in high-flexibility environments

In this paper, we develop models for capacity planning within the framework of stochastic processing times and stochastic demand for different process outcomes in high-flexibility environments. We particularly address stochastic interdependencies between processing times for different processes (inter-process correlation), interdependencies between the capacity consumption (task times) of different executions of the same task in a given production stage (intra-process correlation) as well as interdependencies between the demand for different process outcomes. After presenting the base model, we conduct extensive sensitivity analyses and analyze the main relationships between different model variables. We use process and demand data from the financial industry to demonstrate the applicability and relevance of our findings.