Size, weight and position: ion mobility spectrometry and imaging MS combined

Size, weight and position are three of the most important parameters that describe a molecule in a biological system. Ion mobility spectrometry is capable of separating molecules on the basis of their size or shape, whereas imaging mass spectrometry is an effective tool to measure the molecular weight and spatial distribution of molecules. Recent developments in both fields enabled the combination of the two technologies. As a result, ion-mobility-based imaging mass spectrometry is gaining more and more popularity as a (bio-)analytical tool enabling the determination of the size, weight and position of several molecules simultaneously on biological surfaces. This paper reviews the evolution of ion-mobility-based imaging mass spectrometry and provides examples of its application in analytical studies of biological surfaces

Drosophila type IV collagen mutation associates with immune system activation and intestinal dysfunction

This thesis introduces and explores a new type of representation for low and medium level vision operations called channel representation. The channel representation is a more general way to represent information than e.g. as numerical values, since it allows incorporation of uncertainty, and simultaneous representation of several hypotheses. More importantly it also allows the representation of “no information” when no statement can be given. A channel representation of a scalar value is a vector of channel values, which are generated by passing the original scalar value through a set of kernel functions. The resultant representation is sparse and monopolar. The word sparse signifies that information is not necessarily present in all channels. On the contrary, most channel values will be zero. The word monopolar signifies that all channel values have the same sign, e.g. they are either positive or zero. A zero channel value denotes “no information”, and for non-zero values, the magnitude signifies the relevance. In the thesis, a framework for channel encoding and local decoding of scalar values is presented. Averaging in the channel representation is identified as a regularised sampling of a probability density function. A subsequent decoding is thus a mode estimation technique.' The mode estimation property of channel averaging is exploited in the channel smoothing technique for image noise removal. We introduce an improvement to channel smoothing, called alpha synthesis, which deals with the problem of jagged edges present in the original method. Channel smoothing with alpha synthesis is compared to mean-shift filtering, bilateral filtering, median filtering, and normalized averaging with favourable results. A fast and robust blob-feature extraction method for vector fields is developed. The method is also extended to cluster constant slopes instead of constant regions. The method is intended for view-based object recognition and wide baseline matching. It is demonstrated on a wide baseline matching problem. A sparse scale-space representation of lines and edges is implemented and described. The representation keeps line and edge statements separate, and ensures that they are localised by inhibition from coarser scales. The result is however still locally continuous, in contrast to non-max-suppression approaches, which introduce a binary threshold. The channel representation is well suited to learning, which is demonstrated by applying it in an associative network. An analysis of representational properties of associative networks using the channel representation is made. Finally, a reactive system design using the channel representation is proposed. The system is similar in idea to recursive Bayesian techniques using particle filters, but the present formulation allows learning using the associative networks

Microscope Mode Secondary Ion Mass Spectrometry Imaging with a Timepix Detector

In-vacuum active pixel detectors enable high sensitivity, highly parallel time- and space-resolved detection of ions from complex surfaces. For the first time, a Timepix detector assembly was combined with a Secondary Ion Mass Spectrometer for microscope mode SIMS imaging. Time resolved images from various benchmark samples demonstrate the imaging capabilities of the detector system. The main advantages of the active pixel detector are the higher signal-to-noise ratio and parallel acquisition of arrival time and position. Microscope mode SIMS imaging of biomolecules is demonstrated from tissue sections with the Timepix detector

Oscillating epidemics in a dynamic network model: stochastic and mean-field analysis

An adaptive network model using SIS epidemic propagation with link-type-dependent link activation and deletion is considered. Bifurcation analysis of the pairwise ODE approximation and the network-based stochastic simulation is carried out, showing that three typical behaviours may occur; namely, oscillations can be observed besides disease-free or endemic steady states. The oscillatory behaviour in the stochastic simulations is studied using Fourier analysis, as well as through analysing the exact master equations of the stochastic model. By going beyond simply comparing simulation results to mean-field models, our approach yields deeper insights into the observed phenomena and help better understand and map out the limitations of mean-field models

Effect of Apabetalone on Cardiovascular Events in Diabetes, CKD, and Recent Acute Coronary Syndrome: Results from the BETonMACE Randomized Controlled Trial

CKD and type 2 diabetes mellitus interact to increase the risk of major adverse cardiovascular events (i.e., cardiovascular death, nonfatal myocardial infarction, or stroke) and congestive heart failure. A maladaptive epigenetic response may be a cardiovascular risk driver and amenable to modification with apabetalone, a selective modulator of the bromodomain and extraterminal domain transcription system. We examined this question in a prespecified analysis of BETonMACE, a phase 3 trial.BETonMACE was an event-driven, randomized, double-blind, placebo-controlled trial comparing effects of apabetalone versus placebo on major adverse cardiovascular events and heart failure hospitalizations in 2425 participants with type 2 diabetes and a recent acute coronary syndrome, including 288 participants with CKD with eGFR <60 ml/min per 1.73 m2 at baseline. The primary end point in BETonMACE was the time to the first major adverse cardiovascular event, with a secondary end point of time to hospitalization for heart failure.Median follow-up was 27 months (interquartile range, 20-32 months). In participants with CKD, apabetalone compared with placebo was associated with fewer major adverse cardiovascular events (13 events in 124 patients [11%] versus 35 events in 164 patients [21%]; hazard ratio, 0.50; 95% confidence interval, 0.26 to 0.96) and fewer heart failure-related hospitalizations (three hospitalizations in 124 patients [3%] versus 14 hospitalizations in 164 patients [9%]; hazard ratio, 0.48; 95% confidence interval, 0.26 to 0.86). In the non-CKD group, the corresponding hazard ratio values were 0.96 (95% confidence interval, 0.74 to 1.24) for major adverse cardiovascular events, and 0.76 (95% confidence interval, 0.46 to 1.27) for heart failure-related hospitalization. Interaction of CKD on treatment effect was P=0.03 for major adverse cardiovascular events, and P=0.12 for heart failure-related hospitalization. Participants with CKD showed similar numbers of adverse events, regardless of randomization to apabetalone or placebo (119 [73%] versus 88 [71%] patients), and there were fewer serious adverse events (29% versus 43%; P=0.02) in the apabetalone group.Apabetalone may reduce the incidence of major adverse cardiovascular events in patients with CKD and type 2 diabetes who have a high burden of cardiovascular disease

Repeated-dose toxicity of common ragweed on rats

Ambrosia artemisiifolia L. is an invasive species with highly allergenic pollens. Ragweed originates from North America, but it also occurs and is spreading in Europe, causing seasonal allergic rhinitis for millions of people. Recently, the herb of A. artemisiifolia has gained popularity as medicinal plant and food. The effects of its long-term intake are unknown; there are no toxicological data to support the safe use of this plant. The aim of our study was to assess the repeated dose toxicity of A. artemisiifolia on animals. Ragweed puree was administered in low dose (500 mg/kg b. w.) and high dose (1000 mg/kg b. w.) to male Wistar rats according to 407 OECD Guidelines for the Testing of Chemicals. Clinical symptoms, various blood chemical parameters, body weight and organ weights of the rats were measured. Reduced liver function enzymes (AST, ALT), reduced triglyceride level in the low dose and increased carbamide level in the high dose group were observed. The weight of the liver relative to body weight was significantly reduced in both groups, while the brain weight relative to body weight was significantly elevated in both groups. According to our results, the repeated use of ragweed resulted in toxic effects in rats and these results question the safety of long-term human consumption of common ragweed

Functional Traits Drive Dispersal Interactions Between European Waterfowl and Seeds

Endozoochory by waterfowl is important for a broad range of angiosperms, most of which lack a fleshy fruit. This dispersal function contributes to the formation and maintenance of plant communities and may allow range shifts for plant species under global change. However, our current understanding of what seed or plant traits are important for this dispersal mechanism, and how they relate to variation in waterbird traits, is extremely limited. We addressed this question using a unique dataset identifying the plant species whose seeds are ingested by 31 different waterfowl species in Europe. We used RLQ and fourth-corner analyses to explore relationships between (1) bird morphological and foraging strategy traits, and (2) plant traits related to seed morphology, environmental preferences, and growth form. We then used Generalized Additive Models to identify relationships between plant/seed traits and the number of waterfowl species that disperse them. Although many waterfowl feed intentionally on seeds, available seed trait data provided little explanation for patterns compared to plant traits such as Ellenberg indicators of habitat preference and life form. Geese were associated with terrestrial plants, ingesting seeds as they graze on land. Diving ducks were associated with strictly aquatic plants, ingesting seeds as they feed at greater depths. Dabbling ducks ingest seeds from plants with high light and temperature requirements, especially shoreline and ruderal species growing in or around the dynamic and shallow microhabitats favored by these birds. Overall, the number of waterfowl vector species (up to 13 per plant species) increases for plants with greater soil moisture requirements and salinity tolerance, reflecting the inclination of most waterfowl species to feed in coastal wetlands. Our findings underline the importance of waterfowl dispersal for plants that are not strictly aquatic, as well as for plants associated with high salinities. Furthermore, our results reveal a soil moisture gradient that drives seed-bird interactions, in line with differences between waterfowl groups in their microhabitat preferences along the land-water continuum. This study provides an important advance in our understanding of the interactions that define plant dispersal in wetlands and their surroundings, and of what plants might be affected by ongoing changes in the distributions of waterfowl species

Design and Optimization of Nanostructured Lipid Carrier Containing Dexamethasone for Ophthalmic Use

The aim of this study was to perform a preformulation study of dexamethasone (DXM)-loaded nanostructured lipid carriers (NLCs) for ocular use. Lipid screening was applied to find the most suitable solid and liquid lipids and surfactant for the NLC formulation. The visual observation was proved with XRD measurements for the establishment of the soluble state of DXM. Thermoanalytical measurements indicated that the most relevant depression of the crystallinity index could be ensured when using a 7:3 solid lipid:oil ratio. In order to optimize the NLC composition, a 23 full factorial experimental design was used. It was established that each independent factor (lipid, DXM, and surfactant concentration) had a significant effect on the particle size while in the case of entrapment efficiency, the DXM and surfactant concentrations were significant. Lower surfactant and lipid concentrations could be beneficial because the stability and the entrapment efficacy of NLCs were more favorable. The toxicity tests on human cornea cells indicated good ophthalmic tolerability of NLCs. The in vitro drug release study predicted a higher concentration of the solute DXM on the eye surface while the Raman mapping penetration study on the porcine cornea showed a high concentration of nanocarriers in the hydrophylic stroma layer