Increased expression of bronchial epithelial transient receptor potential vanilloid 1 channels in severe asthma

BACKGROUND: The airway epithelium is exposed to a range of physical and chemical irritants in the environment that are known to trigger asthma. Transient receptor potential (TRP) cation channels play a central role in sensory responses to noxious physical and chemical stimuli. Recent genetic evidence suggests an involvement of transient receptor potential vanilloid 1 (TRPV1), one member of the vanilloid subfamily of TRP channels, in the pathophysiology of asthma. The functional expression of TRPV1 on airway epithelium has yet to be elucidated.

OBJECTIVE: In this study we examined the molecular, functional, and immunohistochemical expression of TRPV1 in asthmatic and healthy airways.

METHODS: Bronchial biopsy specimens and bronchial brushings were obtained from healthy volunteers (n = 18), patients with mild-to-moderate asthma (n = 24), and patients with refractory asthma (n = 22). Cultured primary bronchial epithelial cells from patients with mild asthma (n = 4), nonasthmatic coughers (n = 4), and healthy subjects (n = 4) were studied to investigate the functional role of TRPV1.

RESULTS: Quantitative immunohistochemistry revealed significantly more TRPV1 expression in asthmatic patients compared with healthy subjects, with the greatest expression in patients with refractory asthma (P = .001). PCR and Western blotting analysis confirmed gene and protein expression of TRPV1 in cultured primary bronchial epithelial cells. Patch-clamp electrophysiology directly confirmed functional TRPV1 expression in all 3 groups. In functional assays the TRPV1 agonist capsaicin induced dose-dependent IL-8 release, which could be blocked by the antagonist capsazepine. Reduction of external pH from 7.4 to 6.4 activated a capsazepine-sensitive outwardly rectifying membrane current.

CONCLUSIONS: Functional TRPV1 channels are present in the human airway epithelium and overexpressed in the airways of patients with refractory asthma. These channels might represent a novel therapeutic target for the treatment of uncontrolled asthma.

Tripping Control for Transient Stability in Coordinated Hydro and Wind Generation

Over-frequency generator tripping (OFGT) is used to cut off extra generation to balance power and loads in an isolated system. In this paper the impact of OGFT as a consequence of grid-connected wind farms and under-frequency load shedding (UFLS) is analysed. The paper uses a power system model to demonstrate that wind power fluctuations can readily render OFGT and UFLS maloperation. Using combined hydro and wind generation, the paper proposes a coordinated strategy which resolves problems associated with OFGT and UFLS and preserves system stability.

Optimization of FRT Active Power Performance of a DFIG during Transient Grid Faults

Optimal fault ride-through (FRT) conditions for a doubly-fed induction generator (DFIG) during a transient grid fault are analyzed with special emphasis on improving the active power generation profile. The transition states due to crowbar activation during transient faults are investigated to exploit the maximum power during the fault and post-fault period. It has been identified that operating slip, severity of fault and crowbar resistance have a direct impact on the power capability of a DFIG, and crowbar resistance can be chosen to optimize the power capability. It has been further shown that an extended crowbar period can deliver enhanced inertial response following the transient fault. The converter protection and drive train dynamics have also been analyzed while choosing the optimum crowbar resistance and delivering enhanced inertial support for an extended crowbar period.

Active use of DFIG based Wind Farms for Transient Stability Improvement during Grid Disturbances

The doubly-fed induction generator (DFIG) now represents the dominant technology in wind turbine design. One consequence of this is limited damping and inertial response during transient grid disturbances. A dasiadecoupledpsila strategy is therefore proposed to operate the DFIG grid-side converter (GSC) as a static synchronous compensator (STATCOM) during a fault, supporting the local voltage, while the DFIG operates as a fixed-speed induction generator (FSIG) providing an inertial response. The modeling aspects of the decoupled control strategy, the selection of protection control settings, the significance of the fault location and operation at sub- and super-synchronous speeds are analyzed in detail. In addition, a case study is developed to validate the proposed strategy under different wind penetrations levels. The simulations show that suitable configuration of the decoupled strategy can be deployed to improve system voltage stability and inertial response for a range of scenarios, especially at high wind penetration. The conclusions are placed in context of the practical limitations of the technology employed and the system conditions.

Impact of Wind Generation Mix on Transient Stability for an Interconnected Power System

The rapid growth of wind generation in many European countries is pushing power systems into
uncharted territory. As additional wind generators are installed, the changing generation mix may
impact on power system stability. This paper adopts the New England 39 bus system as a test
system for transient stability analysis. Thermal generator models are based on a likely future plant
mix for existing systems, while varying capacities of fixed-speed induction generators (FSIG) and
doubly-fed induction generators (DFIG) are considered. The main emphasis here has been placed
on the impact of wind technology mix on inter-area oscillations following transient grid
disturbances. In addition, both rotor angle stability and transient voltage stability are examined, and
results are compared with current grid code requirements and standards. Results have shown that
FSIGs can reduce tie-line oscillations and improve damping following a transient disturbance, but
they also cause voltage stability and rotor angle stability problems at high wind penetrations. In
contrast, DFIGs can improve both voltage and rotor angle stability, but their power output
noticeably oscillates during disturbances.

Transient Stability Analysis of a Power System with High Wind Penetration

This paper presents transient stability analysis for a power system with high wind penetration. The transient stability has been evaluated based on two stability criteria: rotor angle stability and voltage stability. A modified IEEE-14 bus system has been used as the main study network and simulations have been conducted at several wind power penetration levels, defined as a fraction of total system generation. A wide range of scenarios have been presented based on the wind farm voltage at the point of connection, i.e. low voltage (LV) distribution level and high voltage (HV) transmission level, and the type of wind generator technology, i.e. fixed speed induction generator (FSIG) and doubly-fed induction generator (DFIG).

Transient Polymorphism in NaCl

We introduce a new, collective variable (CV) that can be used to increase the frequency with which nucleation events are observed in biased atomistic simulations. This CV forces the ions to aggregate into clusters but does not force the ions to order themselves in a particular pattern. We perform metadynamics simulations using this CV in order to examine nucleation in a solution of sodium chloride and find that for small cluster sizes the usual bulk rocksalt structure is less stable than a structure that resembles wurtzite.

Human dental pulp fibroblasts express the "cold-sensing" transient receptor potential channels TRPA1 and TRPM8.

Abstract
INTRODUCTION:
Transient receptor potential (TRP) channels comprise a group of nonselective calcium-permeable cationic channels, which are polymodal sensors of environmental stimuli such as thermal changes and chemicals. TRPM8 and TRPA1 are cold-sensing TRP channels activated by moderate cooling and noxious cold temperatures, respectively. Both receptors have been identified in trigeminal ganglion neurones, and their expression in nonneuronal cells is now the focus of much interest. The aim of this study was to investigate the molecular and functional expression of TRPA1 and TRPM8 in dental pulp fibroblasts.
METHODS:
Human dental pulp fibroblasts were derived from healthy molar teeth. Gene and protein expression was determined by polymerase chain reaction and Western blotting. Cellular localization was investigated by immunohistochemistry, and TRP functionality was determined by Ca(2+) microfluorimetry.
RESULTS:
Polymerase chain reaction and Western blotting showed gene and protein expression of both TRPA1 and TRPM8 in fibroblast cells in culture. Immunohistochemistry studies showed that TRPA1 and TRPM8 immunoreactivity co-localized with the human fibroblast surface protein. In Ca(2+) microfluorimetry studies designed to determine the functionality of TRPA1 and TRPM8 in pulp fibroblasts, we showed increased intracellular calcium ([Ca(2+)](i)) in response to the TRPM8 agonist menthol, the TRPA1 agonist cinnamaldehyde, and to cool and noxious cold stimuli, respectively. The responses to agonists and thermal stimuli were blocked in the presence of specific TRPA1 and TRPM8 antagonists.
CONCLUSIONS:
Human dental pulp fibroblasts express TRPA1 and TRPM8 at the molecular, protein, and functional levels, indicating a possible role for fibroblasts in mediating cold responses in human teeth.

The spotty donor star in the X-ray transient Cen X-4

We accurately determine the fundamental system parameters of the neutron star X-ray transient Cen X-4 solely using phase-resolved high-resolution UV-Visual Echelle Spectrograph spectroscopy. We first determine the radial-velocity curve of the secondary star and then model the shape of the phase-resolved absorption line profiles using an X-ray binary model. The model computes the exact rotationally broadened, phase-resolved spectrum and does not depend on assumptions about the rotation profile, limb-darkening coefficients and the effects of contamination from an accretion disc. We determine the secondary star-to-neutron star binary mass ratio to be 0.1755 ± 0.0025, which is an order of magnitude more accurate than previous estimates. We also constrain the inclination angle to be 32^{+8}_{-2} degrees. Combining these values with the results of the radial-velocity study gives a neutron star mass of 1.94^{+0.37}_{-0.85}M⊙ consistent with previous estimates. Finally, we perform the first Roche tomography reconstruction of the secondary star in an X-ray binary. The tomogram reveals surface inhomogeneities that are due to the presence of cool starspots. A large cool polar spot, similar to that seen in Doppler images of rapidly rotating isolated stars, is present on the Northern hemisphere of the K7 secondary star and we estimate that ~4 percent of the total surface area of the donor star is covered with spots.This evidence for starspots supports the idea that magnetic braking plays an important role in the evolution of low-mass X-ray binaries.

Linking watershed terrain and hydrology to soil chemical properties, microbial communities and impacts on soil organic C in a humid mid-latitude forested watershed

Understanding the response of humid mid-latitude forests to changes in precipitation, temperature, nutrient cycling, and disturbance is critical to improving our predictive understanding of changes in the surface-subsurface energy balance due to climate change. Mechanistic understanding of the effects of long-term and transient moisture conditions are needed to quantify
linkages between changing redox conditions, microbial activity, and soil mineral and nutrient interactions on C cycling and greenhouse gas releases. To illuminate relationships between the soil chemistry, microbial communities and organic C we established transects across hydraulic and topographic gradients in a small watershed with transient moisture conditions. Valley bottoms tend to be more frequently saturated than ridge tops and side slopes which generally are only saturated when shallow storm flow zones are active. Fifty shallow (~36”) soil cores were collected during timeframes representative of low CO2, soil winter conditions and high CO2, soil summer conditions. Cores were subdivided into 240 samples based on pedology and analyses of the geochemical (moisture content, metals, pH, Fe species, N, C, CEC, AEC) and microbial (16S rRNA gene
amplification with Illumina MiSeq sequencing) characteristics were conducted and correlated to watershed terrain and hydrology. To associate microbial metabolic activity with greenhouse gas emissions we installed 17 soil gas probes, collected gas samples for 16 months and analyzed them for CO2 and other fixed and greenhouse gasses. Parallel to the experimental efforts our data is being used to support hydrobiogeochemical process modeling by coupling the Community Land Model (CLM) with a subsurface process model (PFLOTRAN) to simulate processes and interactions from the molecular to watershed scales. Including above ground processes (biogeophysics, hydrology, and vegetation dynamics), CLM provides mechanistic water, energy, and organic matter inputs to the surface/subsurface models, in which coupled biogeochemical reaction
networks are used to improve the representation of below-ground processes. Preliminary results suggest that inclusion of above ground processes from CLM greatly improves the prediction of moisture response and water cycle at the watershed scale.