Dynamical and radiative processes in the Upper Troposphere/Lower Stratosphere

The overall aim of this thesis is to gain a better understanding of certain key attributes and processes in the Upper Troposphere/Lower Stratosphere (UTLS). This work involves exploring the interactions between radiation and dynamics which ultimately affect the destination of chemical constituents. A recently identified feature of the extratropical upper troposphere and lower stratosphere is a region of stable air located just above the tropopause known as the tropopause inversion layer (TIL) which appears as a peak in the stratification. The first main chapter of the thesis focuses on elucidating the large scale dynamical mechanisms which lead to the formation of the TIL by exploring the downward influence of the stratosphere on the UTLS region. Model experiments illustrate that the TIL can arise as a result of the dynamics and the wave driving leads to an upwelling structure that results in a TIL. The maximum value and the shape of the TIL peak vary considerable depending on how the observational data is processed. A common method involves averaging with respect to the tropopause. The details of this averaging are found to affect the shape and strength of the TIL. There exist a double peak in the radiative heating (and correspondingly in the upwelling) in the tropical lower stratosphere and radiative calculations reveal that part of it can be considered as imposed. Radiative process are usually thought of as relaxational with waves being regarded as driving the circulation. Idealised model experiments show that imposing a heating leads to an upwelling and the structure of the latter depends on the aspect ratio of the imposed heating. In such experiments, the waves form part of the response. The last core chapter looks at the relatively large annual cycle in temperatures at around 70 hPa in the UTLS. The annual cycle has peak to peak amplitude of about 7 K in observational data. Using radiative experiments that take into account the time evolution of trace gases, the effect of ozone and water vapour on temperatures is quantified. Water vapour is found to play a significant role in this region, especially lower down in the region of the cold point, with important non local influences on temperature. A further set of experiments reveals how the temperatures are affected by the interactions between the dynamics and radiation

Proteolytic Cleavage and Activation of pro-Macrophage-Stimulating Protein and Upregulation of its Receptor in Tissue Injury

Macrophage stimulating protein (MSP) exists in blood as inactive pro-MSP. Cleavage yields active MSP, the ligand for a membrane receptor (RON) that is expressed on keratinocytes as well as macrophages. Because both cells have roles in tissue injury, we looked for active MSP and expressed RON in wounds. Concentration of pro-MSP + MSP in wound exudates was in the range for optimal activity. Western blot showed that MSP comprised about half the total, in contrast to less than 10% of the total in blood plasma. The presence of MSP was attributed to an exudate pro-MSP convertase that had an inhibitor profile consistent with a trypsin-like serine protease. Exudate evoked morphologic changes in macrophages in vitro like that of MSP. Removal of this activity by an anti-MSP column shows that exudate stimulation of macrophages is due to MSP. RON was infrequently detected in normal skin. RON protein was markedly upregulated in burn wound epidermis and accessory structures, in proliferating cells or differentiated cells, or both. RON was also detected on macrophages and capillaries. Tissue injury leads to cleavage of pro-MSP to MSP, which has potential to act on keratinocytes, macrophages, and capillaries, all components of the wound healing response

Vaccine potential and diversity of the putative cell binding factor (CBF, NMB0345/NEIS1825) protein of Neisseria meningitidis

The cbf gene from Neisseria meningitidis strain MC58 encoding the putative Cell Binding Factor (CBF, NMB0345/NEIS1825) protein was cloned into the pRSETA system and a ~36-kDa recombinant (r)CBF protein expressed in Escherichia coli and purified by metal affinity chromatography. High titres of rCBF antibodies were induced in mice following immunization with rCBF-saline, rCBF-Al(OH)3, rCBF-Liposomes or rCBF-Zwittergent (Zw) 3–14 micelles, both with and without incorporated monophosphoryl lipid A (MPLA) adjuvant. Anti-rCBF sera reacted in western blots of meningococcal lysates with a single protein band of molecular mass ~29.5 kDa, indicative of mature CBF protein, but did not react with a lysate of a ?nmb0345 mutant (CBF-), demonstrating specificity of the murine immune responses. CBF protein was produced by all strains of meningococci studied thus far and the protein was present on the surface of MC58 (CBF+) bacteria, but absent on ?nmb0345 mutant (CBF-) bacteria, as judged by FACS reactivity of anti-rCBF sera. Analysis of the NEIS1825 amino acid sequences from 6644 N. meningitidis isolates with defined Alleles in the pubmlst.org/Neisseria database showed that there were 141 ST types represented and there were 136 different allelic loci encoding 49 non-redundant protein sequences. Only 6/6644 (<0.1%) of N. meningitidis isolates lacked the nmb0345 gene. Amongst serogroup B isolates worldwide, ~68% and ~20% expressed CBF encoded by Allele 1 and 18 respectively, with the proteins sharing >99% amino acid identity. Murine antisera to rCBF in Zw 3–14 micelles + MPLA induced significant serum bactericidal activity (SBA) against homologous Allele 1 and heterologous Allele 18 strains, using both baby rabbit serum complement and human serum complement (h)SBA assays, but did not kill strains expressing heterologous protein encoded by Alelle 2 or 3. Furthermore, variable bactericidal activity was induced by murine antisera against different meningococcal strains in the hSBA assay, which may correlate with variable surface exposure of CBF. Regardless, the attributes of amino acid sequence conservation and protein expression amongst different strains and the ability to induce cross-strain bactericidal antibodies indicates that rCBF could be a potential meningococcal vaccine antigen and merits further testin

The strength of the meridional overturning circulation of the stratosphere.

The distribution of gases such as ozone and water vapour in the stratosphere - which affect surface climate - is influenced by the meridional overturning of mass in the stratosphere, the Brewer-Dobson circulation. However, observation-based estimates of its global strength are difficult to obtain. Here we present two calculations of the mean strength of the meridional overturning of the stratosphere. We analyze satellite data that document the global diabatic circulation between 2007- 2011, and compare these to three re-analysis data sets and to simulations with a state-of-the-art chemistry-climate model. Using measurements of sulfur hexafluoride (SF6) and nitrous oxide, we calculate the global mean diabatic overturning mass flux throughout the stratosphere. In the lower stratosphere, these two estimates agree, and at a potential temperature level of 460 K (about 20 km or 60 hPa in tropics), the global circulation strength is 6.3-7.6 × 109 kg/s. Higher in the atmosphere, only the SF6-based estimate is available, and it diverges from the re-analysis data and simulations. Interpretation of the SF6 data-based estimate is limited because of a mesospheric sink of SF6; however, the reanalyses also differ substantially from each other. We conclude that the uncertainty in the mean meridional overturning circulation strength at upper levels of the stratosphere amounts to at least 100 %

Polarized Secretion of Interleukin (IL)-6 and IL-8 by Human Airway Epithelia 16HBE14o- Cells in Response to Cationic Polypeptide Challenge

BACKGROUND: The airway epithelium participates in asthmatic inflammation in many ways. Target cells of the epithelium can respond to a variety of inflammatory mediators and cytokines. Damage to the surface epithelium occurs following the secretion of eosinophil-derived, highly toxic cationic proteins. Moreover, the surface epithelium itself is responsible for the synthesis and release of cytokines that cause the selective recruitment, retention, and accumulation of various inflammatory cells. To mimic the damage seen during asthmatic inflammation, the bronchial epithelium can be challenged with highly charged cationic polypeptides such as poly-L-arginine. METHODOLOGY/PRINCIPAL FINDINGS: In this study, human bronchial epithelial cells, 16HBE14o- cells, were "chemically injured" by exposing them to poly-l-arginine as a surrogate of the eosinophil cationic protein. Cytokine antibody array data showed that seven inflammatory mediators were elevated out of the 40 tested, including marked elevation in interleukin (IL)-6 and IL-8 secretion. IL-6 and IL-8 mRNA expression levels were elevated as measured with real-time PCR. Cell culture supernatants from apical and basolateral compartments were collected, and the IL-6 and IL-8 production was quantified with ELISA. IL-6 and IL-8 secretion by 16HBE14o- epithelia into the apical compartment was significantly higher than that from the basolateral compartment. Using specific inhibitors, the production of IL-6 and IL-8 was found to be dependent on p38 MAPK, ERK1/2 MAPK, and NF-kappaB pathways. CONCLUSIONS/SIGNIFICANCE: The results clearly demonstrate that damage to the bronchial epithelia by poly-L-arginine stimulates polarized IL-6 and IL-8 secretion. This apically directed secretion of cytokines may play an important role in orchestrating epithelial cell responses to inflammation

Informing antimicrobial management in the context of COVID-19:Understanding the longitudinal dynamics of C-reactive protein and procalcitonin

Background: To characterise the longitudinal dynamics of C-reactive protein (CRP) and Procalcitonin (PCT) in a cohort of hospitalised patients with COVID-19 and support antimicrobial decision-making. Methods: Longitudinal CRP and PCT concentrations and trajectories of 237 hospitalised patients with COVID-19 were modelled. The dataset comprised of 2,021 data points for CRP and 284 points for PCT. Pairwise comparisons were performed between: (i) those with or without significant bacterial growth from cultures, and (ii) those who survived or died in hospital. Results: CRP concentrations were higher over time in COVID-19 patients with positive microbiology (day 9: 236 vs 123 mg/L, p < 0.0001) and in those who died (day 8: 226 vs 152 mg/L, p < 0.0001) but only after day 7 of COVID-related symptom onset. Failure for CRP to reduce in the first week of hospital admission was associated with significantly higher odds of death. PCT concentrations were higher in patients with COVID-19 and positive microbiology or in those who died, although these differences were not statistically significant. Conclusions: Both the absolute CRP concentration and the trajectory during the first week of hospital admission are important factors predicting microbiology culture positivity and outcome in patients hospitalised with COVID-19. Further work is needed to describe the role of PCT for co-infection. Understanding relationships of these biomarkers can support development of risk models and inform optimal antimicrobial strategies

Convergent evolution of hetero‐oligomeric cellulose synthesis complexes in mosses and seed plants

In seed plants, cellulose is synthesized by rosette‐shaped cellulose synthesis complexes (CSCs) that are obligate hetero‐oligomeric, comprising three non‐interchangeable cellulose synthase (CESA) isoforms. The moss Physcomitrella patens has rosette CSCs and seven CESAs, but its common ancestor with seed plants had rosette CSCs and a single CESA gene. Therefore, if P. patens CSCs are hetero‐oligomeric, then CSCs of this type evolved convergently in mosses and seed plants. Previous gene knockout and promoter swap experiments showed that PpCESAs from class A (PpCESA3 and PpCESA8) and class B (PpCESA6 and PpCESA7) have non‐redundant functions in secondary cell wall cellulose deposition in leaf midribs, whereas the two members of each class are redundant. Based on these observations, we proposed the hypothesis that the secondary class A and class B PpCESAs associate to form hetero‐oligomeric CSCs. Here we show that transcription of secondary class A PpCESAs is reduced when secondary class B PpCESAs are knocked out and vice versa, as expected for genes encoding isoforms that occupy distinct positions within the same CSC. The class A and class B isoforms co‐accumulate in developing gametophores and co‐immunoprecipitate, suggesting that they interact to form a complex in planta. Finally, secondary PpCESAs interact with each other, whereas three of four fail to self‐interact when expressed in two different heterologous systems. These results are consistent with the hypothesis that obligate hetero‐oligomeric CSCs evolved independently in mosses and seed plants and we propose the constructive neutral evolution hypothesis as a plausible explanation for convergent evolution of hetero‐oligomeric CSCs

How temporal patterns in rainfall determine the geomorphology and carbon fluxes of tropical peatlands

Tropical peatlands now emit hundreds of megatons of carbon dioxide per year because of human disruption of the feedbacks that link peat accumulation and groundwater hydrology. However, no quantitative theory has existed for how patterns of carbon storage and release accompanying growth and subsidence of tropical peatlands are affected by climate and disturbance. Using comprehensive data from a pristine peatland in Brunei Darussalam, we show how rainfall and groundwater flow determine a shape parameter (the Laplacian of the peat surface elevation) that specifies, under a given rainfall regime, the ultimate, stable morphology, and hence carbon storage, of a tropical peatland within a network of rivers or canals. We find that peatlands reach their ultimate shape first at the edges of peat domes where they are bounded by rivers, so that the rate of carbon uptake accompanying their growth is proportional to the area of the still-growing dome interior. We use this model to study how tropical peatland carbon storage and fluxes are controlled by changes in climate, sea level, and drainage networks. We find that fluctuations in net precipitation on timescales from hours to years can reduce long-term peat accumulation. Our mathematical and numerical models can be used to predict long-term effects of changes in temporal rainfall patterns and drainage networks on tropical peatland geomorphology and carbon storage

Role of the Adiponectin Binding Protein, T-Cadherin (Cdh13), in Allergic Airways Responses in Mice

Adiponectin is an adipose derived hormone that declines in obesity. We have previously shown that exogenous administration of adiponectin reduces allergic airways responses in mice. T-cadherin (T-cad; Cdh13) is a binding protein for the high molecular weight isoforms of adiponectin. To determine whether the beneficial effects of adiponectin on allergic airways responses require T-cad, we sensitized wildtype (WT), T-cadherin deficient (T-cad−/−) and adiponectin and T-cad bideficient mice to ovalbumin (OVA) and challenged the mice with aerosolized OVA or PBS. Compared to WT, T-cad−/− mice were protected against OVA-induced airway hyperresponsiveness, increases in BAL inflammatory cells, and induction of IL-13, IL-17, and eotaxin expression. Histological analysis of the lungs of OVA-challenged T-cad−/− versus WT mice indicated reduced inflammation around the airways, and reduced mucous cell hyperplasia. Combined adiponectin and T-cad deficiency reversed the effects of T-cad deficiency alone, indicating that the observed effects of T-cad deficiency require adiponectin. Compared to WT, serum adiponectin was markedly increased in T-cad−/− mice, likely because adiponectin that is normally sequestered by endothelial T-cad remains free in the circulation. In conclusion, T-cad does not mediate the protective effects of adiponectin. Instead, mice lacking T-cad have reduced allergic airways disease, likely because elevated serum adiponectin levels act on other adiponectin signaling pathways

An Unbiased Survey of 500 Nearby Stars for Debris Disks: A JCMT Legacy Program

We present the scientific motivation and observing plan for an upcoming detection survey for debris disks using the James Clerk Maxwell Telescope. The SCUBA-2 Unbiased Nearby Stars (SUNS) Survey will observe 500 nearby main sequence and sub-giant stars (100 of each of the A, F, G, K and M spectral classes) to the 850 micron extragalactic confusion limit to search for evidence of submillimeter excess, an indication of circumstellar material. The survey distance boundaries are 8.6, 16.5, 22, 25 and 45 pc for M, K, G, F and A stars, respectively, and all targets lie between the declinations of -40 deg to 80 deg. In this survey, no star will be rejected based on its inherent properties: binarity, presence of planetary companions, spectral type or age. This will be the first unbiased survey for debris disks since IRAS. We expect to detect ~125 debris disks, including ~50 cold disks not detectable in current shorter wavelength surveys. A substantial amount of complementary data will be required to constrain the temperatures and masses of discovered disks. High resolution studies will likely be required to resolve many of the disks. Therefore, these systems will be the focus of future observational studies using a variety of observatories to characterize their physical properties. For non-detected systems, this survey will set constraints (upper limits) on the amount of circumstellar dust, of typically 200 times the Kuiper Belt mass, but as low as 10 times the Kuiper Belt mass for the nearest stars in the sample (approximately 2 pc).Comment: 11 pages, 7 figures (3 color), accepted by the Publications of the Astronomical Society of the Pacifi