Evaluating Arctic meteorology modelled with the Unified Model and Integrated Forecasting System

By synthesising remote-sensing measurements made in the central Arctic into a model-gridded Cloudnet cloud product, we evaluate how well the Met Office Unified Model (UM) and the European Centre for Medium-Range Weather Forecasting (ECMWF) Integrated Forecasting System (IFS) capture Arctic clouds and their associated interactions with the surface energy balance and the thermodynamic structure of the lower troposphere. This evaluation was conducted using a 4-week observation period from the Arctic Ocean 2018 expedition, where the transition from sea ice melting to freezing conditions was measured. Three different cloud schemes were tested within a nested limited-area model (LAM) configuration of the UM – two regionally operational single-moment schemes (UM_RA2M and UM_RA2T) and one novel double-moment scheme (UM_CASIM-100) – while one global simulation was conducted with the IFS, utilising its default cloud scheme (ECMWF_IFS). Consistent weaknesses were identified across both models, with both the UM and IFS overestimating cloud occurrence below 3 km. This overestimation was also consistent across the three cloud configurations used within the UM framework, with >90 % mean cloud occurrence simulated between 0.15 and 1 km in all the model simulations. However, the cloud microphysical structure, on average, was modelled reasonably well in each simulation, with the cloud liquid water content (LWC) and ice water content (IWC) comparing well with observations over much of the vertical profile. The key microphysical discrepancy between the models and observations was in the LWC between 1 and 3 km, where most simulations (all except UM_RA2T) overestimated the observed LWC. Despite this reasonable performance in cloud physical structure, both models failed to adequately capture cloud-free episodes: this consistency in cloud cover likely contributes to the ever-present near-surface temperature bias in every simulation. Both models also consistently exhibited temperature and moisture biases below 3 km, with particularly strong cold biases coinciding with the overabundant modelled cloud layers. These biases are likely due to too much cloud-top radiative cooling from these persistent modelled cloud layers and were consistent across the three UM configurations tested, despite differences in their parameterisations of cloud on a sub-grid scale. Alarmingly, our findings suggest that these biases in the regional model were inherited from the global model, driving a cause–effect relationship between the excessive low-altitude cloudiness and the coincident cold bias. Using representative cloud condensation nuclei concentrations in our double-moment UM configuration while improving cloud microphysical structure does little to alleviate these biases; therefore, no matter how comprehensive we make the cloud physics in the nested LAM configuration used here, its cloud and thermodynamic structure will continue to be overwhelmingly biased by the meteorological conditions of its driving model

Phenotype and Genetics of Progressive Sensorineural Hearing Loss (Snhl1) in the LXS Set of Recombinant Inbred Strains of Mice

Progressive sensorineural hearing loss is the most common form of acquired hearing impairment in the human population. It is also highly prevalent in inbred strains of mice, providing an experimental avenue to systematically map genetic risk factors and to dissect the molecular pathways that orchestrate hearing in peripheral sensory hair cells. Therefore, we ascertained hearing function in the inbred long sleep (ILS) and inbred short sleep (ISS) strains. Using auditory-evoked brain stem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements, we found that ISS mice developed a high-frequency hearing loss at twelve weeks of age that progressed to lower frequencies by 26 weeks of age in the presence of normal endocochlear potentials and unremarkable inner ear histology. ILS mice exhibited milder hearing loss, showing elevated thresholds and reduced DPOAEs at the higher frequencies by 26 weeks of age. To map the genetic variants that underlie this hearing loss we computed ABR thresholds of 63 recombinant inbred stains derived from the ISS and ILS founder strains. A single locus was linked to markers associated with ISS alleles on chromosome 10 with a highly significant logarithm of odds (LOD) score of 15.8. The 2-LOD confidence interval spans ∼4 Megabases located at position 54–60 Mb. This locus, termed sensorineural hearing loss 1 (Snhl1), accounts for approximately 82% of the phenotypic variation. In summary, this study identifies a novel hearing loss locus on chromosome 10 and attests to the prevalence and genetic heterogeneity of progressive hearing loss in common mouse strains

Localization of the Cochlear Amplifier in Living Sensitive Ears

BACKGROUND: To detect soft sounds, the mammalian cochlea increases its sensitivity by amplifying incoming sounds up to one thousand times. Although the cochlear amplifier is thought to be a local cellular process at an area basal to the response peak on the spiral basilar membrane, its location has not been demonstrated experimentally. METHODOLOGY AND PRINCIPAL FINDINGS: Using a sensitive laser interferometer to measure sub-nanometer vibrations at two locations along the basilar membrane in sensitive gerbil cochleae, here we show that the cochlea can boost soft sound-induced vibrations as much as 50 dB/mm at an area proximal to the response peak on the basilar membrane. The observed amplification works maximally at low sound levels and at frequencies immediately below the peak-response frequency of the measured apical location. The amplification decreases more than 65 dB/mm as sound levels increases. CONCLUSIONS AND SIGNIFICANCE: We conclude that the cochlea amplifier resides at a small longitudinal region basal to the response peak in the sensitive cochlea. These data provides critical information for advancing our knowledge on cochlear mechanisms responsible for the remarkable hearing sensitivity, frequency selectivity and dynamic range

Similarity of Traveling-Wave Delays in the Hearing Organs of Humans and Other Tetrapods

Transduction of sound in mammalian ears is mediated by basilar-membrane waves exhibiting delays that increase systematically with distance from the cochlear base. Most contemporary accounts of such “traveling-wave” delays in humans have ignored postmortem basilar-membrane measurements in favor of indirect in vivo estimates derived from brainstem-evoked responses, compound action potentials, and otoacoustic emissions. Here, we show that those indirect delay estimates are either flawed or inadequately calibrated. In particular, we argue against assertions based on indirect estimates that basilar-membrane delays are much longer in humans than in experimental animals. We also estimate in vivo basilar-membrane delays in humans by correcting postmortem measurements in humans according to the effects of death on basilar-membrane vibrations in other mammalian species. The estimated in vivo basilar-membrane delays in humans are similar to delays in the hearing organs of other tetrapods, including those in which basilar membranes do not sustain traveling waves or that lack basilar membranes altogether

A critical experimental study of the classical tactile threshold theory

<p>Abstract</p> <p>Background</p> <p>The tactile sense is being used in a variety of applications involving tactile human-machine interfaces. In a significant number of publications the classical threshold concept plays a central role in modelling and explaining psychophysical experimental results such as in stochastic resonance (SR) phenomena. In SR, noise enhances detection of sub-threshold stimuli and the phenomenon is explained stating that the required amplitude to exceed the sensory threshold barrier can be reached by adding noise to a sub-threshold stimulus. We designed an experiment to test the validity of the classical vibrotactile threshold. Using a second choice experiment, we show that individuals can order sensorial events below the level known as the classical threshold. If the observer's sensorial system is not activated by stimuli below the threshold, then a second choice could not be above the chance level. Nevertheless, our experimental results are above that chance level contradicting the definition of the classical tactile threshold.</p> <p>Results</p> <p>We performed a three alternative forced choice detection experiment on 6 subjects asking them first and second choices. In each trial, only one of the intervals contained a stimulus and the others contained only noise. According to the classical threshold assumptions, a correct second choice response corresponds to a guess attempt with a statistical frequency of 50%. Results show an average of 67.35% (STD = 1.41%) for the second choice response that is not explained by the classical threshold definition. Additionally, for low stimulus amplitudes, second choice correct detection is above chance level for any detectability level.</p> <p>Conclusions</p> <p>Using a second choice experiment, we show that individuals can order sensorial events below the level known as a classical threshold. If the observer's sensorial system is not activated by stimuli below the threshold, then a second choice could not be above the chance level. Nevertheless, our experimental results are above that chance level. Therefore, if detection exists below the classical threshold level, then the model to explain the SR phenomenon or any other tactile perception phenomena based on the psychophysical classical threshold is not valid. We conclude that a more suitable model of the tactile sensory system is needed.</p

PI3Kγ Protects from Myocardial Ischemia and Reperfusion Injury through a Kinase-Independent Pathway

BACKGROUND: PI3Kgamma functions in the immune compartment to promote inflammation in response to G-protein-coupled receptor (GPCR) agonists and PI3Kgamma also acts within the heart itself both as a negative regulator of cardiac contractility and as a pro-survival factor. Thus, PI3Kgamma has the potential to both promote and limit M I/R injury. METHODOLOGY/PRINCIPAL FINDINGS: Complete PI3Kgamma-/- mutant mice, catalytically inactive PI3KgammaKD/KD (KD) knock-in mice, and control wild type (WT) mice were subjected to in vivo myocardial ischemia and reperfusion (M I/R) injury. Additionally, bone-marrow chimeric mice were constructed to elucidate the contribution of the inflammatory response to cardiac damage. PI3Kgamma-/- mice exhibited a significantly increased infarction size following reperfusion. Mechanistically, PI3Kgamma is required for activation of the Reperfusion Injury Salvage Kinase (RISK) pathway (AKT/ERK1/2) and regulates phospholamban phosphorylation in the acute injury response. Using bone marrow chimeras, the cardioprotective role of PI3Kgamma was mapped to non-haematopoietic cells. Importantly, this massive increase in M I/R injury in PI3Kgamma-/- mice was rescued in PI3Kgamma kinase-dead (PI3KgammaKD/KD) knock-in mice. However, PI3KgammaKD/KD mice exhibited a cardiac injury similar to wild type animals, suggesting that specific blockade of PI3Kgamma catalytic activity has no beneficial effects. CONCLUSIONS/SIGNIFICANCE: Our data show that PI3Kgamma is cardioprotective during M I/R injury independent of its catalytic kinase activity and that loss of PI3Kgamma function in the hematopoietic compartment does not affect disease outcome. Thus, clinical development of specific PI3Kgamma blockers should proceed with caution

An intergenerational study of perceptions of changes in active free play among families from rural areas of Western Canada

Background: Children's engagement in active free play has declined across recent generations. Therefore, the purpose of this study was to examine perceptions of intergenerational changes in active free play among families from rural areas. We addressed two research questions: (1) How has active free play changed across three generations? (2) What suggestions do participants have for reviving active free play? Methods: Data were collected via 49 individual interviews with members of 16 families (15 grandparents, 16 parents, and 18 children) residing in rural areas/small towns in the Province of Alberta (Canada). Interview recordings were transcribed verbatim and subjected to thematic analysis guided by an ecological framework of active free play. Results: Factors that depicted the changing nature of active free play were coded in the themes of less imagination/more technology, safety concerns, surveillance, other children to play with, purposeful physical activity, play spaces/organized activities, and the good parenting ideal. Suggestions for reviving active free play were coded in the themes of enhance facilities to keep kids entertained, provide more opportunities for supervised play, create more community events, and decrease use of technology. Conclusions: These results reinforce the need to consider multiple levels of social ecology in the study of active free play, and highlight the importance of community-based initiatives to revive active free play in ways that are consistent with contemporary notions of good parentin