A role for TASK-1 (KCNK3) channels in the chemosensory control of breathing

Acid-sensitive K+ channels of the tandem P-domain K+-channel family (TASK-1 and TASK-3) have been implicated in peripheral and central respiratory chemosensitivity; however, because of the lack of decisive pharmacological agents, the final proof of the role of the TASK channel in the chemosensory control of breathing has been missing. In the mouse, TASK-1 and TASK-3 channels are dispensable for central respiratory chemosensitivity (Mulkey et al., 2007Go). Here, we have used knock-out animals to determine whether TASK-1 and TASK-3 channels play a role in the carotid body function and chemosensory control of breathing exerted by the carotid body chemoreceptors. Ventilatory responses to hypoxia (10% O2 in inspired air) and moderate normoxic hypercapnia (3–6% CO2 in inspired air) were significantly reduced in TASK-1 knock-out mice. In contrast, TASK-3-deficient mice showed responses to both stimuli that were similar to those developed by their wild-type counterparts. TASK-1 channel deficiency resulted in a marked reduction of the hypoxia (by 49%)- and CO2 (by 68%)-evoked increases in the carotid sinus nerve chemoafferent discharge recorded in the in vitro superfused carotid body/carotid sinus nerve preparations. Deficiency in both TASK-1 and TASK-3 channels increased baseline chemoafferent activity but did not cause a further reduction of the carotid body chemosensory responses. These observations provide direct evidence that TASK-1 channels contribute significantly to the increases in the carotid body chemoafferent discharge in response to a decrease in arterial PO2 or an increase in PCO2/[H+]. TASK-1 channels therefore play a key role in the control of ventilation by peripheral chemoreceptors

Design of a horizontal neutron reflectometer for the European Spallation Source

A design study of a horizontal neutron reflectometer adapted to the general baseline of the long pulse European Spallation Source (ESS) is presented. The instrument layout comprises solutions for the neutron guide, high-resolution pulse shaping and beam bending onto a sample surface being so far unique in the field of reflectometry. The length of this instrument is roughly 55 m, enabling $\delta \lambda / \lambda$ resolutions from 0.5% to 10%. The incident beam is focussed in horizontal plane to boost measurements of sample sizes of 1*1 cm{^2} and smaller with potential beam deflection in both downward and upward direction. The range of neutron wavelengths untilized by the instrument is 2 to 7.1 (12.2, ...) {\AA}, if every (second, ...) neutron source ulse is used. Angles of incidence can be set between 0{\deg} and 9{\deg} with a total accessible q-range from 4*10^{-3} {\AA}^{-1} up to 1 {\AA}^{-1}. The instrument operates both in {\theta}/{\theta} (free liquid surfaces) and {\theta}/2{\theta} (solid/liquid, air/solid interfaces) geometry. The experimental setup will in particular enable direct studies on ultrathin films (d ~ 10 {\AA}) and buried monolayers to multilayered structures of up to 3000 {\AA} total thickness. The horizontal reflectometer will further foster investigations of hierarchical systems from nanometer to micrometer length scale, as well as their kinetics and dynamical properties, in particular under load (shear, pressure, external fields). Polarization and polarization analysis as well as the GISANS option are designed as potential modules to be implemented separately in the generic instrument layout. The instrument is highly flexible and offers a variety of different measurement modes. With respect to its mechanical components the instrument is exclusively based on current technology. Risks of failure for the chosen setup are minimum.Comment: Matched to the version submitted to Nuclear Instruments and Methods

The clinical application of PET/CT: a contemporary review

The combination of positron emission tomography (PET) scanners and x-ray computed tomography (CT) scanners into a single PET/CT scanner has resulted in vast improvements in the diagnosis of disease, particularly in the field of oncology. A decade on from the publication of the details of the first PET/CT scanner, we review the technology and applications of the modality. We examine the design aspects of combining two different imaging types into a single scanner, and the artefacts produced such as attenuation correction, motion and CT truncation artefacts. The article also provides a discussion and literature review of the applications of PET/CT to date, covering detection of tumours, radiotherapy treatment planning, patient management, and applications external to the field of oncology

Quantitative evaluation of polymer gel dosimeters by broadband ultrasound attenuation

Ultrasound has been examined previously as an alternative readout method for irradiated polymer gel dosimeters, with authors reporting varying dose response to ultrasound transmission measurements. In this current work we extend previous work to measure the broadband ultrasound attenuation (BUA) response of irradiated PAGAT gel dosimeters, using a novel ultrasound computed tomography system

Parametric study of transport aircraft systems cost and weight

The results of a NASA study to develop production cost estimating relationships (CERs) and weight estimating relationships (WERs) for commercial and military transport aircraft at the system level are presented. The systems considered correspond to the standard weight groups defined in Military Standard 1374 and are listed. These systems make up a complete aircraft exclusive of engines. The CER for each system (or CERs in several cases) utilize weight as the key parameter. Weights may be determined from detailed weight statements, if available, or by using the WERs developed, which are based on technical and performance characteristics generally available during preliminary design. The CERs that were developed provide a very useful tool for making preliminary estimates of the production cost of an aircraft. Likewise, the WERs provide a very useful tool for making preliminary estimates of the weight of aircraft based on conceptual design information

MpTCP1 controls cell proliferation and redox processes in Marchantia polymorpha

TCP transcription factors are key regulators of angiosperm cell proliferation processes. It is unknown whether their regulatory growth capacities are conserved across land plants, which we examined in liverworts, one of the earliest diverging land plant lineages. We generated knockout mutants for MpTCP1, the single TCP‐P clade gene in Marchantia polymorpha, and characterized its function conducting cell proliferation and morphological analyses as well as mRNA expression, transcriptome, chemical and DNA binding studies. Mptcp1ge lines show a reduced vegetative thallus growth and extra tissue formation in female reproductive structures. Additionally, mutant plants reveal increased H2O2 levels and an enhanced pigmentation in the thallus caused by formation of secondary metabolites, such as aminochromes. MpTCP1 proteins interact redox‐dependently with DNA and regulate the expression of a comprehensive redox network, comprising enzymes involved in H2O2 metabolism. MpTCP1 regulates Marchantia growth context‐dependently. Redox sensitivity of the DNA binding capacity of MpTCP1 proteins provides a mechanism to respond to altered redox conditions. Our data suggest that MpTCP1 activity could thereby have contributed to diversification of land plant morphologies and to adaptations to abiotic and biotic challenges, experienced by liverworts during early land plant colonization