Inhibition of breathing after surfactant depletion is achieved at a higher arterial PCO(2 )during ventilation with liquid than with gas

BACKGROUND: Inhibition of phrenic nerve activity (PNA) can be achieved when alveolar ventilation is adequate and when stretching of lung tissue stimulates mechanoreceptors to inhibit inspiratory activity. During mechanical ventilation under different lung conditions, inhibition of PNA can provide a physiological setting at which ventilatory parameters can be compared and related to arterial blood gases and pH. OBJECTIVE: To study lung mechanics and gas exchange at inhibition of PNA during controlled gas ventilation (GV) and during partial liquid ventilation (PLV) before and after lung lavage. METHODS: Nine anaesthetised, mechanically ventilated young cats (age 3.8 ± 0.5 months, weight 2.3 ± 0.1 kg) (mean ± SD) were studied with stepwise increases in peak inspiratory pressure (PIP) until total inhibition of PNA was attained before lavage (with GV) and after lavage (GV and PLV). Tidal volume (V(t)), PIP, oesophageal pressure and arterial blood gases were measured at inhibition of PNA. One way repeated measures analysis of variance and Student Newman Keuls-tests were used for statistical analysis. RESULTS: During GV, inhibition of PNA occurred at lower PIP, transpulmonary pressure (Ptp) and Vt before than after lung lavage. After lavage, inhibition of inspiratory activity was achieved at the same PIP, Ptp and Vt during GV and PLV, but occurred at a higher PaCO(2 )during PLV. After lavage compliance at inhibition was almost the same during GV and PLV and resistance was lower during GV than during PLV. CONCLUSION: Inhibition of inspiratory activity occurs at a higher PaCO(2 )during PLV than during GV in cats with surfactant-depleted lungs. This could indicate that PLV induces better recruitment of mechanoreceptors than GV

The properties of V838 Mon in 2002 November

We present the results of modelling the 0.45--1 micron spectral energy distribution of V838 Mon for 2002 November. Synthetic spectra were calculated using the NextGen model atmospheres of Hauschildt et al. (1999), which incorporate line lists for H2O, TiO, CrH, FeH, CO, and MgH, as well as the VALD atomic line list. Fits to the observed spectra show that, in 2002 November, the effective temperature of V838 Mon was approximately 2000 +/-100 K. Our theoretical spectra show a comparatively weak dependence on log g. Preliminary analysis of the hot star observed together with V838 Mon shows it to be a normal B3V dwarf.Comment: 7 pages, 4 figs, accepted by A&

Quantitative analysis of WC stars: Constraints on neon abundances from ISO/SWS spectroscopy

Neon abundances are derived in four Galactic WC stars -- gamma Vel (WR11, WC8+O7.5III), HD156385 (WR90, WC7), HD192103 (WR135, WC8), and WR146 (WC5+O8) - using mid-infrared fine structure lines obtained with ISO/SWS. Stellar parameters for each star are derived using a non-LTE model atmospheric code (Hillier & Miller 1998) together with ultraviolet (IUE), optical (INT, AAT) and infrared (UKIRT, ISO) spectroscopy. In the case of gamma Vel, we adopt results from De Marco et al. (2000), who followed an identical approach. ISO/SWS datasets reveal the [NeIII] 15.5um line in each of our targets, while [NeII] 12.8um, [SIV] 10.5um and [SIII] 18.7um are observed solely in gamma Vel. Using a method updated from Barlow et al. (1988) to account for clumped winds, we derive Ne/He=3-4x10^-3 by number, plus S/He=6x10^-5 for gamma Vel. Neon is highly enriched, such that Ne/S in gamma Vel is eight times higher than cosmic values. However, observed Ne/He ratios are a factor of two times lower than predictions of current evolutionary models of massive stars. An imprecise mass-loss and distance were responsible for the much greater discrepancy in neon content identified by Barlow et al. Our sample of WC5--8 stars span a narrow range in T* (=55--71kK), with no trend towards higher temperature at earlier spectral type, supporting earlier results for a larger sample by Koesterke & Hamann (1995). Stellar luminosities range from 100,000 to 500,000 Lo, while 10^-5.1 < Mdot/(Mo/yr) < 10^-4.5, adopting clumped winds, in which volume filling factors are 10%. In all cases, wind performance numbers are less than 10, significantly lower than recent estimates. Carbon abundances span 0.08 < C/He < 0.25 by number, while oxygen abundances remain poorly constrained.Comment: 16 pages,7 figures accepted for MNRA

Facilitating Knowledge Visualisation as Communication and Knowledge Transfer Mechanism in Postgraduate Learning

Advances in technology and subsequent access to inexpensive software have made visualisation, as a method of knowledge creation and transfer, more accessible. Visualisations have been used to support knowledge representation and transfer in teaching but the focus has primarily been on creating visualisations for learner consumption. The idea of students becoming active participants in producing visualisations, as part of knowledge creation and learning, has largely been overlooked. The study reported here investigated the use of visualisation for summarising knowledge at postgraduate level. The student’s need to assimilate and organise knowledge is an important part of their learning. We suggest that it would be useful for students to learn how to produce knowledge visualisations as part of this activity. The production is an act of knowledge creation, which can improve their comprehension of the research literature. Producing visualisations is not necessarily straightforward and it is therefore advisable to scaffold the process. We propose a faded-struts learning process that gradually removes scaffolding as the learner masters the principles and becomes more adept. The contribution of this research is to present the idea of providing worked examples and faded examples to support postgraduate learning. This helps postgraduates to craft knowledge visualisations so that they can slowly become more proficient and independent. Due to the ubiquity of mobile devices we propose providing this support on these devices, incorporating their unique constraints and affordances in our learning process. This is essentially a proof of concept paper, suggesting how the idea could be realised. Further work is necessary to test the idea with students and to extend the repertoire of mobile learning (m-learning) visualisation tasks.College of Engineering, Science and Technolog

Downstream signalling and specific inhibition of c-MET/HGF pathway in small cell lung cancer: implications for tumour invasion

The c-MET receptor can be overexpressed, amplified, or mutated in solid tumours including small cell lung cancer (SCLC). In c-MET-overexpressing SCLC cell line NCI-H69, hepatocyte growth factor (HGF) dramatically induced c-MET phosphorylation at phosphoepitopes pY1230/1234/1235 (catalytic tyrosine kinase), pY1003 (juxtamembrane), and also of paxillin at pY31 (CRKL-binding site). We utilised a global proteomics phosphoantibody array approach to identify further c-MET/HGF signal transduction intermediates in SCLC. Strong HGF induction of specific phosphorylation sites in phosphoproteins involved in c-MET/HGF signal transduction was detected, namely adducin-α [S724], adducin-γ [S662], CREB [S133], ERK1 [T185/Y187], ERK1/2 [T202/Y204], ERK2 [T185/Y187], MAPKK (MEK) 1/2 [S221/S225], MAPKK (MEK) 3/6 [S189/S207], RB [S612], RB1 [S780], JNK [T183/Y185], STAT3 [S727], focal adhesion kinase (FAK) [Y576/S722/S910], p38α-MAPK [T180/Y182], and AKT1[S473] and [T308]. Conversely, inhibition of phosphorylation by HGF in protein kinase C (PKC), protein kinase R (PKR), and also CDK1 was identified. Phosphoantibody-based immunohistochemical analysis of SCLC tumour tissue and microarray established the role of c-MET in SCLC biology. This supports a role of c-MET activation in tumour invasive front in the tumour progression and invasion involving FAK and AKT downstream. The c-MET serves as an attractive therapeutic target in SCLC, as shown through small interfering RNA (siRNA) and selective prototype c-MET inhibitor SU11274, inhibiting the phosphorylation of c-MET itself and its downstream molecules such as AKT, S6 kinase, and ERK1/2. Investigation of mechanisms of invasion and, ultimately, metastasis in SCLC would be very useful with these signal transduction molecules

First Human Model of In Vitro Candida albicans Persistence within Granuloma for the Reliable Study of Host-Fungi Interactions

BACKGROUND: The balance between human innate immune system and Candida albicans virulence signaling mechanisms ultimately dictates the outcome of fungal invasiveness and its pathology. To better understand the pathophysiology and to identify fungal virulence-associated factors in the context of persistence in humans, complex models are indispensable. Although fungal virulence factors have been extensively studied in vitro and in vivo using different immune cell subsets and cell lines, it is unclear how C. albicans survives inside complex tissue granulomas. METHODOLOGY/PRINCIPAL FINDING: We developed an original model of in vitro human granuloma, reproducing the natural granulomatous response to C. albicans. Persistent granulomas were obtained when the ratio of phagocytes to fungi was high. This in vitro fungal granuloma mimics natural granulomas, with infected macrophages surrounded by helper and cytotoxic T lymphocytes. A small proportion of granulomas exhibited C. albicans hyphae. Histological and time-lapse analysis showed that C. albicans blastoconidia were located within the granulomas before hyphae formation. Using staining techniques, fungal load calculations, as well as confocal and scanning electron microscopy, we describe the kinetics of fungal granuloma formation. We provide the first direct evidence that C. albicans are not eliminated by immunocompetent cells inside in vitro human granulomas. In fact, after an initial candicidal period, the remaining yeast proliferate and persist under very complex immune responses. CONCLUSIONS/SIGNIFICANCE: Using an original in vitro model of human fungal granuloma, we herein present the evidence that C. albicans persist and grow into immunocompetent granulomatous structures. These results will guide us towards a better understanding of fungal invasiveness and, henceforth, will also help in the development of better strategies for its control in human physiological conditions

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12- q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

Assessing Arboreal Adaptations of Bird Antecedents: Testing the Ecological Setting of the Origin of the Avian Flight Stroke

The origin of avian flight is a classic macroevolutionary transition with research spanning over a century. Two competing models explaining this locomotory transition have been discussed for decades: ground up versus trees down. Although it is impossible to directly test either of these theories, it is possible to test one of the requirements for the trees-down model, that of an arboreal paravian. We test for arboreality in non-avian theropods and early birds with comparisons to extant avian, mammalian, and reptilian scansors and climbers using a comprehensive set of morphological characters. Non-avian theropods, including the small, feathered deinonychosaurs, and Archaeopteryx, consistently and significantly cluster with fully terrestrial extant mammals and ground-based birds, such as ratites. Basal birds, more advanced than Archaeopteryx, cluster with extant perching ground-foraging birds. Evolutionary trends immediately prior to the origin of birds indicate skeletal adaptations opposite that expected for arboreal climbers. Results reject an arboreal capacity for the avian stem lineage, thus lending no support for the trees-down model. Support for a fully terrestrial ecology and origin of the avian flight stroke has broad implications for the origin of powered flight for this clade. A terrestrial origin for the avian flight stroke challenges the need for an intermediate gliding phase, presents the best resolved series of the evolution of vertebrate powered flight, and may differ fundamentally from the origin of bat and pterosaur flight, whose antecedents have been postulated to have been arboreal and gliding