Castleman disease and lymphocytic interstitial pneumonia: a complex diagnostic and management challenge

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Efficient geocasting in opportunistic networks

With the proliferation of smartphones and their advanced connectivity capabilities, opportunistic networks have gained a lot of traction during the past years; they are suitable for increasing network capacity and sharing ephemeral, localised content. They can also offload traffic from cellular networks to device-to-device ones, when cellular networks are heavily stressed. Opportunistic networks can play a crucial role in communication scenarios where the network infrastructure is inaccessible due to natural disasters, large-scale terrorist attacks or government censorship. Geocasting, where messages are destined to specific locations (casts) instead of explicitly identified devices, has a large potential in real world opportunistic networks, however it has attracted little attention in the context of opportunistic networking. In this paper we propose Geocasting Spray And Flood (GSAF), a simple and efficient geocasting protocol for opportunistic networks. GSAF follows an elegant and flexible approach where messages take random walks towards the destination cast. Messages that are routed away from the destination cast are extinct when devices’ buffers get full, freeing space for new messages to be delivered. In GSAF, casts do not have to be pre-defined; instead users can route messages to arbitrarily defined casts. GSAF does that in a privacy-preserving fashion. We also present DA-GSAF, a Direction-Aware extension of GSAF in which messages are forwarded to encountered nodes based on whether a node is moving towards their destination cast. In DA-GSAF only the direction of a mobile node is revealed to other devices. We experimentally evaluate our protocols and compare their performance to prominent geocasting protocols in a very wide set of scenarios, including different maps, mobility models and user populations. Both GSAF and DA-GSAF perform significantly better compared to all other studied protocols, in terms of message delivery ratio, latency and network overhead. DA-GSAF is particularly efficient in sparse scenarios minimising network overhead compared to all other studied protocols. Both GSAF and DA-GSAF perform very well for a wide range of device/user populations indicating that our proposal is viable for crowded and sparse opportunistic networks

GSAF: efficient and flexible geocasting for opportunistic networks

With the proliferation of smartphones and their advanced connectivity capabilities, opportunistic networks have gained a lot of traction during the past years; they are suitable for increasing network capacity and sharing ephemeral, localised content. They can also offload traffic from cellular networks to device-to-device ones, when cellular networks are heavily stressed. Opportunistic networks can play a crucial role in communication scenarios where the network infrastructure is inaccessible due to natural disasters, large-scale terrorist attacks or government censorship. Geocasting, where messages are destined to specific locations (casts) instead of explicitly identified devices, has a large potential in real world opportunistic networks, however it has attracted little attention in the context of opportunistic networking. In this paper we propose Geocasting Spray And Flood (GSAF), a simple but efficient and flexible geocasting protocol for opportunistic, delay-tolerant networks. GSAF follows a simple but elegant and flexible approach where messages take random walks towards the destination cast. Messages that follow directions away from the cast are extinct when the device buffer gets full, freeing space for new messages to be delivered. In GSAF, casts do not have to be pre-defined; instead users can route messages to arbitrarily defined casts. Our extensive evaluation shows that GSAF is efficient, in terms of message delivery ratio and latency as well as network overhead

Endothelin-1 and the use of induced sputum to investigate its role in airway diseases

Endothelin (ET)-1 is a 21-amino acid peptide which has been the subject of intense interest since its discovery in 1988. It has a number of properties which may be important in physiology and pathophysiology, including potential relevance to airway diseases. A putative role for ET-1 in asthma has been proposed, and we sought to examine this further, as well as to extend our investigations to other respiratory diseases, including chronic obstructive pulmonary disease and cystic fibrosis. The technique of sputum induction has been developed recently as a non-invasive method of obtaining airway secretions for analysis, and we have applied this to the investigation of the role of ET-1 in diseases involving the airway. We have demonstrated for the first time that ET-1 is a highly potent bronchoconstrictor with a prolonged duration of action when administered by aerosol in asthma, and that asthmatics exhibit bronchial hyperreactivity to ET-1 compared with non-asthmatic subjects, but we found no evidence of an acute inflammatory airway response at 30 minutes or 4 hours following ET-l-induced bronchoconstriction in asthma, assessed by analysis of cell counts and soluble mediators in induced sputum. The bronchoconstrictor activity of ET-1 was not potentiated by an infusion of angiotensin II in stable asthmatics, despite animal evidence of potentiation, although the possibility of such interaction remains in acute severe asthma, where plasma angiotensin II levels are elevated. We did not find increased levels of ET-1 in induced sputum in mild asthmatics compared with non-asthmatic subjects, nor was there a fall in sputum ET-1 comparing samples obtained during acute severe asthma with those obtained in convalescence, although sputum and saliva levels of ET-1 are greater than plasma ET-1, suggesting local production within the respiratory tract. Examination of sputum ET-1 following allergen challenge in asthma showed a trend towards an increase in sputum ET-1 after allergen challenge, with a relationship between the increase in sputum ET-1 and the extent of sputum eosinophilia, suggesting a relationship between asthmatic airway inflammation and ET- 1 release. Sputum ET-1 is increased in smokers without lung disease, and in subjects with chronic obstructive pulmonary disease (COPD), with a trend towards a fall in sputum ET-1 comparing acute exacerbation with convalescence. Finally, we have demonstrated a marked increase in sputum ET-1 in patients with cystic fibrosis compared with healthy subjects. We conclude from this series of studies that there is continuing evidence for a role for ET-1 in a number of diseases affecting the airway, and speculate that drugs which oppose the action of ET-1 may have a role in the treatment of these conditions

Demand for low carbon food products

The emissions associated with food consumption make up approximately 20-30 percent of Scotland’s total greenhouse gas emissions (GHG). Reducing demand for high carbon footprint food products may provide an effective instrument for reducing GHG emissions. However, there is concern that using consumption based taxes may also have negative consequences on nutrition. Therefore, this thesis investigates the likely effect of carbon consumption taxes on GHG emissions and the resulting impact on nutrient consumption. The data used for the analysis are the Scottish part of Kantar Worldpanel data for the UK for the period 2006-2013 along with various sources of carbon footprint and nutrient data. This thesis models a carbon consumption tax which is based on the carbon footprint of the products of interest. The impact of the taxes on demand for food products were measured through the use of demand systems. Two forms of demand systems were used: Almost Ideal Demand System (AIDS) and an Exact Affine Stone Index (EASI) which allow for the estimation of price elasticities based on time series data. These Marshallian price elasticities were then used for estimating carbon footprint and nutrient elasticities which allow for the estimated change in GHG emissions (represented as carbon emissions) and nutrients. The price elasticities were particularly important for identifying the substitutes and complements of the different food products. This is useful as some food products such as poultry have a lower carbon footprint relative to beef products. The results suggest that applying carbon consumption taxes would likely reduce carbon emissions though the reduction is relatively small. The net effect of taxing all major food products would likely reduce emissions by 543,208.75 tCO2e/y which represents approximately five percent of the total emissions in Scotland attributed to food consumption (no land use change considered). However, taxing only meat and milk food products could reduce emissions by approximately 1.6 million tCO2e/y. While this reduction is much larger than when all food products are taxed, it is considered that modelling all the major food products offers a more realistic understanding of how households will change their demand for the different food products. The effect on nutrient consumption with regards to taxing all food products suggests that households with lower socioeconomic status would likely experience some favourable changes in terms of a reduction in sugar and energy. Though a negative distributional effect is likely to occur when considering the decreased consumption of vitamin D and the increased consumption of salt. Therefore, a carbon consumption tax is estimated to reduce food based GHG emissions by a relatively small amount. Despite the mainly positive effect on nutrient intake, policy makers are still likely to be cautious when considering this instrument because of the relatively small (compared to other studies) reduction in GHG emissions

Transposase subunit architecture and its relationship to genome size and the rate of transposition in prokaryotes and eukaryotes

Cut-and-paste transposons are important tools for mutagenesis, gene-delivery and DNA sequencing applications. At the molecular level, the most thoroughly understood are Tn5 and Tn10 in bacteria, and mariner and hAT elements in eukaryotes. All bacterial cut-and-paste transposases characterized to date are monomeric prior to interacting with the transposon end, while all eukaryotic transposases are multimers. Although there is a limited sample size, we proposed that this defines two pathways for transpososome assembly which distinguishes the mechanism of the bacterial and eukaryotic transposons. We predicted that the respective pathways would dictate how the rate of transposition is related to transposase concentration and genome size. Here, we have tested these predictions by creating a single-chain dimer version of the bacterial Tn5 transposase. We show that artificial dimerization switches the transpososome assembly pathway from the bacterial-style to the eukaryotic-style. Although this had no effect in vitro, where the transposase does not have to search far to locate the transposon ends, it increased the rate of transposition in bacterial and HeLa cell assays. However, in contrast to the mariner elements, the Tn5 single-chain dimer remained unaffected by over-production inhibition, which is an emergent property of the transposase subunit structure in the mariner elements

Cytotoxicity and radiosensitizing activity of the fatty acid synthase inhibitor C75 is enhanced by blocking fatty acid uptake in prostate cancer cells

Prostate cancers, like many other types of cancer, express elevated levels of fatty acid synthase (FASN) to make more fatty acids, which are required for energy, signaling, and proliferation. Because inhibition of FASN has been shown to sensitize tumors to chemotherapy and radiation, we studied the effect of C75, a radiosensitizing FASN inhibitor, and compared its single agent and radiosensitizing activities in 2 prostate cancer cell lines, PC3 and LNCaP, with alternative FASN inhibitors that have progressed into clinical trials. We also investigated the effect of serum and fatty acid supplementation on responses to FASN inhibitors, probing expression of key proteins related to fatty acid uptake in response to FASN inhibition, irradiation, and serum lipid concentration and how this may be modulated to increase the potency of C75. We demonstrated that C75 was the only FASN inhibitor to sensitize cells to ionizing radiation; no sensitization was apparent with FASN inhibitors TVB-3166 or Orlistat. The prostate cancer cell lines were able to take up fatty acids from the culture medium, and the availability of fatty acids affected sensitivity of these cells to C75 but not the other FASN inhibitors tested. C75 also increased expression of fatty acid transporter proteins FATP1 and CD36. Furthermore, blocking CD36 with antibody increased the sensitivity of cells to C75. We suggest that the potency of C75 is affected by fatty acid availability and that the effectiveness of FASN inhibitors in combination with ionizing radiation can be further enhanced by regulating fatty acid uptake