Decreases in arterial blood oxygen stimulate increases in minute ventilation via activation of peripheral and central respiratory structures. This study evaluates the role of endothelial nitric oxide ...synthase (eNOS) in the expression of the ventilatory responses during and following a hypoxic gas challenge (HXC, 10% O
, 90% N
) in freely moving male and female wild-type (WT) C57BL6 and eNOS knock-out (eNOS-/-) mice. Exposure to HXC caused an array of responses (of similar magnitude and duration) in both male and female WT mice such as, rapid increases in frequency of breathing, tidal volume, minute ventilation and peak inspiratory and expiratory flows, that were subject to pronounced roll-off. The responses to HXC in male eNOS-/- mice were similar to male WT mice. In contrast, several of the ventilatory responses in female eNOS-/- mice (e.g., frequency of breathing, and expiratory drive) were greater compared to female WT mice. Upon return to room-air, male and female WT mice showed similar excitatory ventilatory responses (i.e., short-term potentiation phase). These responses were markedly reduced in male eNOS-/- mice, whereas female eNOS-/- mice displayed robust post-HXC responses that were similar to those in female WT mice. Our data demonstrates that eNOS plays important roles in (1) ventilatory responses to HXC in female compared to male C57BL6 mice; and (2) expression of post-HXC responses in male, but not female C57BL6 mice. These data support existing evidence that sex, and the functional roles of specific proteins (e.g., eNOS) have profound influences on ventilatory processes, including the responses to HXC.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The roles of endothelial nitric oxide synthase (eNOS) in the ventilatory responses during and after a hypercapnic gas challenge (HCC, 5% CO
, 21% O
, 74% N
) were assessed in freely-moving female and ...male wild-type (WT) C57BL6 mice and eNOS knock-out (eNOS-/-) mice of C57BL6 background using whole body plethysmography. HCC elicited an array of ventilatory responses that were similar in male and female WT mice, such as increases in breathing frequency (with falls in inspiratory and expiratory times), and increases in tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives. eNOS-/- male mice had smaller increases in minute ventilation, peak inspiratory flow and inspiratory drive, and smaller decreases in inspiratory time than WT males. Ventilatory responses in female eNOS-/- mice were similar to those in female WT mice. The ventilatory excitatory phase upon return to room-air was similar in both male and female WT mice. However, the post-HCC increases in frequency of breathing (with decreases in inspiratory times), and increases in tidal volume, minute ventilation, inspiratory drive (i.e., tidal volume/inspiratory time) and expiratory drive (i.e., tidal volume/expiratory time), and peak inspiratory and expiratory flows in male eNOS-/- mice were smaller than in male WT mice. In contrast, the post-HCC responses in female eNOS-/- mice were equal to those of the female WT mice. These findings provide the first evidence that the loss of eNOS affects the ventilatory responses during and after HCC in male C57BL6 mice, whereas female C57BL6 mice can compensate for the loss of eNOS, at least in respect to triggering ventilatory responses to HCC.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Enduring sustainability challenges requires a new model of collective leadership that embraces critical reflection, inclusivity and care. Leadership collectives can support a move in academia from ...metrics to merits, from a focus on career to care, and enact a shift from disciplinary to inter- and trans-disciplinary research. Academic organisations need to reorient their training programs, work ethics and reward systems to encourage collective excellence and to allow space for future leaders to develop and enact a radically re-imagined vision of how to lead as a collective with care for people and the planet.
Full text
Available for:
CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The recent rise of neogeography and citizen sensing has increased the opportunities for the use of crowdsourcing as a means to acquire data to support geographical research. The value of the ...resulting volunteered geographic information is, however, often limited by concerns associated with its quality and the degree to which the contributing data sources may be trusted. Here, information on the quality of sources of volunteered geographic information was derived using a latent class analysis. The volunteered information was on land cover interpreted visually from satellite sensor images and the main focus was on the labeling of 299 sites by seven of the 65 volunteers who contributed to an Internet‐based collaborative project. Using the information on land cover acquired by the multiple volunteers it was shown that the relative, but not absolute, quality of the data from different volunteers could be characterized accurately. Additionally, class‐specific variations in the quality of the information provided by a single volunteer could be characterized by the analysis. The latent class analysis, therefore, was able to provide information on the quality of information provided on an inter‐ and intra‐volunteer basis.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Crowdsourcing is a popular means of acquiring data, but the use of such data is limited by concerns with its quality. This is evident within cartography and geographical sciences more generally, with ...the quality of volunteered geographic information (VGI) recognized as a major challenge to address if the full potential of citizen sensing in mapping applications is to be realized. Here, a means to characterize the quality of volunteers, based only on the data they contribute, was used to explore issues connected with the quantity and quality of volunteers for attribute mapping. The focus was on data in the form of annotations or class labels provided by volunteers who visually interpreted an attribute, land cover, from a series of satellite sensor images. A latent class model was found to be able to provide accurate characterisations of the quality of volunteers in terms of the accuracy of their labelling, irrespective of the number of cases that they labelled. The accuracy with which a volunteer could be characterized tended to increase with the number of volunteers contributing but was typically good at all but small numbers of volunteers. Moreover, the ability to characterize volunteers in terms of the quality of their labelling could be used constructively. For example, volunteers could be ranked in terms of quality which could then be used to select a sub-set as input to a subsequent mapping task. This was particularly important as an identified subset of volunteers could undertake a task more accurately than when part of a larger group of volunteers. The results highlight that both the quantity and quality of volunteers need consideration and that the use of VGI may be enhanced through information on the quality of the volunteers derived entirely from the data provided without any additional information.
Full text
Available for:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
THGEM-based photon detectors for the upgrade of COMPASS RICH-1 Alexeev, M.; Birsa, R.; Bradamante, F. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
12/2013, Volume:
732
Journal Article
Peer reviewed
Open access
New Cherenkov photon detectors are being developed for the upgrade of COMPASS RICH-1. The detectors are based on THGEMs, arranged in a three layer architecture, with a CsI film on the first layer ...acting as a reflective photocathode. The response of THGEMs with various geometries under different conditions has been studied and photon detector prototypes have been built, tested in laboratory and operated during test beam runs providing a typical gain of 105 and a time resolution of better than 10ns. A photon detector prototype with 300×300mm2 active area, operated at the CERN PS T10 test beam in November 2012, has confirmed the validity of this novel technology and has allowed further studies of the detector response.
•The COMPASS THGEM R&D team has performed systematic studies and parameter optimization for THGEMs to be used in RICH applications.•A triple-THGEM photon detector with 300×300mm2 active area has been successfully tested at the CERN PS T10 test-beam.•A photon detector prototype based on coupling THGEM and Micromegas has provided encouraging results in laboratory tests.•For the upgrade of COMPASS RICH-1 a set of THGEM-based photon detectors will be produced.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
THGEM based photon detector for Cherenkov imaging applications Alexeev, M.; Birsa, R.; Bradamante, F. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
05/2010, Volume:
617, Issue:
1
Journal Article
Peer reviewed
We are developing a single photon detector for Cherenkov imaging counters. This detector is based on the use of THGEM electron multipliers in a multilayer design. The major goals of our project are ...ion feedback suppression down to a few per cent, large gain, fast response, insensitivity to magnetic fields, and a large detector size.
We report about the project status and perspectives. In particular, we present a systematic study of the THGEM response as a function of geometrical parameters, production techniques and the gas mixture composition. The first figures obtained from measuring the response of a CsI coated THGEM to single photons are presented.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Evidence from mouse chronic viral infection models suggests that CD8
T cell subsets characterized by distinct expression levels of the receptor PD-1 diverge in their state of exhaustion and potential ...for reinvigoration by PD-1 blockade. However, it remains unknown whether T cells in human cancer adopt a similar spectrum of exhausted states based on PD-1 expression levels. We compared transcriptional, metabolic and functional signatures of intratumoral CD8
T lymphocyte populations with high (PD-1
), intermediate (PD-1
) and no PD-1 expression (PD-1
) from non-small-cell lung cancer patients. PD-1
T cells showed a markedly different transcriptional and metabolic profile from PD-1
and PD-1
lymphocytes, as well as an intrinsically high capacity for tumor recognition. Furthermore, while PD-1
lymphocytes were impaired in classical effector cytokine production, they produced CXCL13, which mediates immune cell recruitment to tertiary lymphoid structures. Strikingly, the presence of PD-1
cells was strongly predictive for both response and survival in a small cohort of non-small-cell lung cancer patients treated with PD-1 blockade. The characterization of a distinct state of tumor-reactive, PD-1-bright lymphocytes in human cancer, which only partially resembles that seen in chronic infection, provides potential avenues for therapeutic intervention.
PDF
