The irradiated ISM of ULIRGs

The nuclei of ULIRGs harbor massive young stars, an accreting central black hole, or both. Results are presented for molecular gas that is exposed to X-rays (1-100 keV, XDRs) and far-ultraviolet radiation (6-13.6 eV, PDRs). Attention is paid to species like HCO+, HCN, HNC, OH, H2O and CO. Line ratios of HCN/HCO+ and HNC/HCN discriminate between PDRs and XDRs. Very high J (>10) CO lines, observable with HIFI/Herschel, discriminate very well between XDRs and PDRs. In XDRs, it is easy to produce large abundances of warm (T>100 K) H2O and OH. In PDRs, only OH is produced similarly well.Comment: 5 pages, 6 figures, to appear in: IAU Symposium 242 Astrophysical Masers and their Environment

Molecular properties of (U)LIRGs: CO, HCN, HNC and HCO+

The observed molecular properties of a sample of FIR-luminous and OH megamaser (OH-MM) galaxies have been investigated. The ratio of high and low-density tracer lines is found to be determined by the progression of the star formation in the system. The HCO+/HCN and HCO+/HNC line ratios are good proxies for the density of the gas, and PDR and XDR sources can be distinguished using the HNC/HCN line ratio. The properties of the OH-MM sources in the sample can be explained by PDR chemistry in gas with densities higher than 10^5.5 cm^-3, confirming the classical OH-MM model of IR pumped amplification with (variable) low gains.Comment: 5 pages, 2 figures, to appear in: IAU Symposium 242 Astrophysical Masers and their Environment

CO+ in M 82: A Consequence of Irradiation by X-rays

Based on its strong CO+ emission it is argued that the M 82 star-burst galaxy is exposed to a combination of FUV and X-ray radiation. The latter is likely to be the result of the star-burst superwind, which leads to diffuse thermal emission at ~0.7 keV, and a compact hard, 2-10 keV, source (but not an AGN). Although a photon-dominated region (FUV) component is clearly present in the nucleus of M 82, and capable of forming CO+, only X-ray irradiated gas of density 10^3-10^5 cm^-3 can reproduce the large, ~(1-4)x10^13 cm^-2, columns of CO+ that are observed toward the proto-typical star-burst M 82. The total X-ray luminosity produced by M 82 is weak, ~10^41 erg s^-1, but this is sufficient to drive the formation of CO+.Comment: added discussion on more recent X-ray observation

An IC-compatible polyimide pressure sensor with capacitive readout

A capacitive differential pressure sensor has been developed. The process used for the fabrication of the sensor is IC-compatible, meaning that the device potentially can be integrated on one chip with a suitable signal-conditioning circuit. A sensor for a differential pressure of ±1 bar has been fabricated and tested with a frequency-modulated detection circuit, and good agreement is found with the theoretical model of the sensor. A nominal sensitivity ¿C/C of 17% has been measured for a positive differential pressure of 1 bar. The resolution of the complete detection system is 2.5 mbar (250 Pa)

Interactions of lactobacilli with the host immune system

The aim of this thesis was to better understand the molecular mechanism of host res-ponses to probiotics. Probiotics can be used to stimulate or regulate immune responses in epithelial and immune cells of the intestinal mucosa and generate beneficial effects on the immune system. Carefully selected probiotics are able to steer the activity of the immune response in a predetermined manner by increasing or decreasing the activity of different aspects of the immune system (e.g. development and activity of T helper subsets). Beneficial effects of strains of probiotics have been established in the treatment and prevention of various intestinal disorders, including allergic diseases and diarrhea. However the precise molecular mechanisms and the strain dependent factors involved are poorly understood. Here in vitro molecular studies and in vivo mechanistic studies were combined in different mouse models to generate new insights into the beneficial mechanisms of selected lactobacilli and identify novel bacterial genes influencing the immune response. A further aim was to investigate the predictive value of in vitro immune assays for the effects of probiotics in vivo. Chapter 1and chapter 2 describe the current knowledge and understanding of the immunomodulatory effects of different probiotic species and strains on mucosal immune system, dendritic cells (DCs) and the adaptive immune system. The relevance and the implications of in vitro studies for clinical trials or mechanistic research in animal mo-dels are discussed. Chapter 3and chapter 4 present new insights gained from research on the strain-dependent factors involved in probiotic immune modulation. Extensive variation was observed in the immune responses to 42 L. plantarum strains. These results were used to identify genetic loci that correlated with levels of induced cytokines (such as IL-10 or IL-12) following co-culture with DCs (chapter 3) or peripheral blood mononuclear cells (PBMCs) (chapter 4). This in silico “gene-trait matching” approach led to the identification of several candidate genes in the L. plantarum genome that might modulate the immune cytokine response to L. plantarum. Selective gene deletions mutants were constructed for the candidate genes in L. plantarum WCFS1 and compared to the wild-type strain in immune assays with PBMCs and DCs. The predicted phenotype of the genetic knock-out was confirmed for most of the candidate loci including genes encoding an N-acetyl-glucosamine/galactosamine phosphotransferase system, the LamBDCA quorum sensing system, a predicted transcriptional regulator gene (lp_2991) and components of the plantaricin (bacteriocin) biosynthesis and transport pathway. Transcriptome analysis and qPCR data showed that transcript level of gtcA3, which is predicted to be involved in the glycosylation of cell wall teichoic acids, was substantially increased in the lp_2991 deletion mutant (44- and 29-fold respectively). In vitroassays for pre-screening of candidate probiotics would benefit from standar-dized methods and cryopreservation techniques for immature DCs (iDCs) or precursor monocytes. Literature on the effects of cryopreservation and thawing of monocytes or monocyte-derived iDCs suggested that this strategy might be useful although bacteria had not been previously used as a stimulus. Thus in chapter 5 we investigated the effects of cryopreservation and thawing of precursor monocytes and iDCs on the maturation and immune response of DCs to potential probiotic strains and bacterial TLR agonists. Surface markers CD83 and CD86 were expressed at similar levels on iDCs generated from cryopreserved or freshly isolated monocytes. Cryopreservation of iDCs led to slightly decreased expression of CD86 and CD83 compared to freshly generated iDCs prepared from unfrozen cells but this did not affect the capacity of DCs to acquire fully mature characteristics after stimulation. In contrast the cytokine response to lipoteichoic acid and bacterial stimulation was altered by cryopreservation of monocytes or iDCs, particularly for IL-12 which was decreased up to 250 fold or even not detected at all. Cryopreservation also decreased TNF-α and IL-1β production in stimulated iDCs but to a lesser extent than for IL-12, depending on the maturation factors used. The amounts of IL-10 produced by stimulated iDCs were increased up to 3.6 fold when iDCs were cryopreserved, but decreased up to 90 fold when generated from cryopreserved monocytes. Immature DCs are often used to investigate the immunomodulatory properties of probiotics and here we showed for the first time that cryopreserved monocytes and cryopreserved iDCs have a skewed cytokine response to microbial stimulation. Therefore we consider that standardization of probiotic screening assays by the use of cryopreservation methods is currently not applicable. The detailed method for generating human monocyte derived DC described in chapter 5 may however be useful for developing standardized immune assays. In chapter 6 we screened the immunomodulatory properties of 28 commercially available bacterial strains in vitro using human PBMCs and investigated selected strains for their in vivo immunomodulatory potential in an established mouse peanut allergy model. The 28 probiotic strains induced highly variable cytokine profiles in PBMCs. L. salivarius HMI001 (HMI001), L. casei Shirota (LCS) and L. plantarum WCFS1 (WCFS1) were selected for further investigation due to their distinct patterns of IL-10, IL-12 and IFN-γ induction. Prophylactic treatment with both HMI001 and LCS attenuated the Th2 phenotype in the mouse model (reduced mast cell responses and ex vivo IL-4 and/or IL-5 production). In contrast, WCFS1 augmented the Th2 phenotype (increased mast cell and antibody responses and ex vivo IL-4 production). In vitro PBMC screening was useful in selecting strains with anti-inflammatory and Th1 skewing properties. In the case of HMI001 (inducing a high IL-10/IL-12 ratio) and LCS (inducing high amounts of IFN-γ and IL-12) partial protection was seen in a mouse peanut allergy model. However, certain strains may worsen the allergic reaction as shown in the case of WCFS1. This approach indicated that pre-selection of candidate probiotics using in vitro immune assays is useful for selecting strains for translational research in humans. Probiotics have been shown to increase the efficacy of different vaccines and can be easily consumed in food, and therefore probiotics might be useful in the improvement of current mucosal vaccines. In chapter 7 we have investigated the mechanisms behind the effect of lactobacilli on humoral responses to an intranasal vaccine. In addition to L. rhamnosus GG we selected 6 strains of Lactobacillus plantarum which have strikingly different immunomodulatory properties in vitro and TLR-2/6 activating properties. This selection was based on the approach outlined in chapter 3 and chapter 4 examining the in vitro immune responses of human monocyte derived DCs and PBMCs to 42 different L. plantarum strains. First we established an influenza vaccination model in Balb/c mice that would be sensitive to immunomodulation by lactobacilli, which allowed potential up- and down-regulation by the lactobacilli of the immune response. Strain WCFS1, that induced the lowest IL-10 to IL-12 cytokine ratio in DC co-culture significantly increased vaccine-specific antibody responses to the intranasal vaccine compared to the vaccine control group. Several Lactobacillus strains appeared to increase delayed-type hypersensitivity responses after vaccination compared to the vaccine control group indicating increased Th1-mediated vaccine responses. For strain LMG18021 this was also reflected in the significantly higher vaccine-specific IgG2a to IgG1 antibody ratio. LMG18021, CIP104448 and CIP104450 which have the highest IL-10 to IL-12 ratios of the strains tested, significantly enhanced the ex vivo vaccine-specific induction of IL-10, IL-17A, IL-6 and IL-4 in MLN cells. B1839 which was included as negative control, as it was a low cytokine inducer, did not enhance the vaccine-specific antibody or immune response indicating that the immune-stimulatory properties are important in mediating effects on the vaccine response. Further research is needed to demonstrate that these effects on the vaccine response impact on protection from influenza challenge and to validate the immunomodulatory mechanisms involved. Nevertheless, the in vivo studies described in this thesis support other publications proposing that in vitro immune assays can be useful for predicting which candidate probiotic strains will be most effective in vivo. Chapter 8 completes this thesis with an overview of the most important findings of this thesis and discusses possible research limitations and future research perspectives. We stress the importance of proper strain selection using in vitro assays, and the use of strategies to identify novel immunomodulatory factors. The results described in this thesis support the rationale of using in vitro co-culture assays for selection of candidate probiotics for in vivo animal experiments or human trials. </p

Star Formation in Extreme Environments: The Effects of Cosmic Rays and Mechanical Heating

Context: Molecular data of extreme environments, such as Arp 220, but also NGC 253, show evidence for extremely high cosmic ray (CR) rates (10^3-10^4 * Milky Way) and mechanical heating from supernova driven turbulence. Aims: The consequences of high CR rates and mechanical heating on the chemistry in clouds are explored. Methods: PDR model predictions are made for low, n=10^3, and high, n=10^5.5 cm^-3, density clouds using well-tested chemistry and radiation transfer codes. Column densities of relevant species are discussed, and special attention is given to water related species. Fluxes are shown for fine-structure lines of O, C+, C, and N+, and molecular lines of CO, HCN, HNC, and HCO+. A comparison is made to an X-ray dominated region model. Results: Fine-structure lines of [CII], [CI], and [OI] are remarkably similar for different mechanical heating and CR rates, when already exposed to large amounts of UV. HCN and H2O abundances are boosted for very high mechanical heating rates, while ionized species are relatively unaffected. OH+ and H2O+ are enhanced for very high CR rates zeta > 5 * 10^-14 s^-1. A combination of OH+, OH, H2O+, H2O, and H3O+ trace the CR rates, and are able to distinguish between enhanced cosmic rays and X-rays.Comment: 13 pages, 8 figures, A&A accepte

Diagnostics of the molecular component of PDRs with mechanical heating. II: line intensities and ratios

CO observations in active galactic nuclei and star-bursts reveal high kinetic temperatures. Those environments are thought to be very turbulent due to dynamic phenomena such as outflows and high supernova rates. We investigate the effect of mechanical heating (MH) on atomic fine-structure and molecular lines, and their ratios. We use those ratios as a diagnostic to constrain the amount of MH in an object and also study its significance on estimating the H2 mass. Equilibrium PDRs models were used to compute the thermal and chemical balance for the clouds. The equilibria were solved for numerically using the optimized version of the Leiden PDR-XDR code. Large velocity gradient calculations were done as post-processing on the output of the PDR models using RADEX. High-J CO line ratios are very sensitive to MH. Emission becomes at least one order of magnitude brighter in clouds with n~10^5~cm^-3 and a star formation rate of 1 Solar Mass per year (corresponding to a MH rate of 2 * 10^-19 erg cm^-3 s^-1). Emission of low-J CO lines is not as sensitive to MH, but they do become brighter in response to MH. Generally, for all of the lines we considered, MH increases excitation temperatures and decreases the optical depth at the line centre. Hence line ratios are also affected, strongly in some cases. Ratios involving HCN are a good diagnostic for MH, such as HCN(1-0)/CO(1-0) and HCN(1-0)/HCO^+(1-0). Both ratios increase by a factor 3 or more for a MH equivalent to > 5 percent of the surface heating, as opposed to pure PDRs. The first major conclusion is that low-J to high-J intensity ratios will yield a good estimate of the MH rate (as opposed to only low-J ratios). The second one is that the MH rate should be taken into account when determining A_V or equivalently N_H, and consequently the cloud mass. Ignoring MH will also lead to large errors in density and radiation field estimates.Comment: 38 pages, to appear in A&

Diagnostics of the Molecular Component of PDRs with Mechanical Heating

Context. Multitransition CO observations of galaxy centers have revealed that significant fractions of the dense circumnuclear gas have high kinetic temperatures, which are hard to explain by pure photon excitation, but may be caused by dissipation of turbulent energy. Aims. We aim to determine to what extent mechanical heating should be taken into account while modelling PDRs. To this end, the effect of dissipated turbulence on the thermal and chemical properties of PDRs is explored. Methods. Clouds are modelled as 1D semi-infinite slabs whose thermal and chemical equilibrium is solved for using the Leiden PDR-XDR code. Results. In a steady-state treatment, mechanical heating seems to play an important role in determining the kinetic temperature of the gas in molecular clouds. Particularly in high-energy environments such as starburst galaxies and galaxy centers, model gas temperatures are underestimated by at least a factor of two if mechanical heating is ignored. The models also show that CO, HCN and H2 O column densities increase as a function of mechanical heating. The HNC/HCN integrated column density ratio shows a decrease by a factor of at least two in high density regions with n \sim 105 cm-3, whereas that of HCN/HCO+ shows a strong dependence on mechanical heating for this same density range, with boosts of up to three orders of magnitude. Conclusions. The effects of mechanical heating cannot be ignored in studies of the molecular gas excitation whenever the ratio of the star formation rate to the gas density is close to, or exceeds, 7 \times 10-6 M yr-1 cm4.5 . If mechanical heating is not included, predicted column densities are underestimated, sometimes even by a few orders of magnitude. As a lower bound to its importance, we determined that it has non-negligible effects already when mechanical heating is as little as 1% of the UV heating in a PDR.Comment: 26 pages, 14 figures in the text and 13 figures as supplementary material. Accepted for publication in A&

Sit down at the ball game: how trade barriers make the world less food secure

This paper analyses the impacts of trade policy responses to rising world food prices by carrying out a series of stylised experiments in the wheat market using a world trade model, GTAP. The sequence of events that is modelled comprises a negative wheat supply shock and subsequent implementation of an export tax by a major net exporter and a reduction in import tariffs by a small importer. The effects of trade policy responses are contrasted with those of full liberalisation of the wheat market. At the core are the (opposite) effects on producers and consumers, as well as the terms-of-trade and trade tax revenue effects. Food security is shown to depend crucially on changes in prices but also in incomes that are associated with changes in factor returns. The results reveal that major net exporters are generally better off when implementing export taxes for food security purposes. Large exporting countries export price instability causing world food prices to rise further. Net importing countries lose out and have limited leeway to reduce tariffs or subsidise imports. Liberalising wheat trade mitigates rising prices and contributes to food security, but to the detriment of production in Africa and Asia, making them more dependent on and vulnerable to changes in the world market. Concerted action at the WTO forum is required, notably clarifying and sharpening the rules regarding export measures.food security; world food crisis; international grain trade; trade measures; trade liberalisation; CGE modelling