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Early life adversity (ELA) is associated with a higher risk for diseases in adulthood. Changes in the immune system have been proposed to underlie this association. Although higher levels of inflammation and immunosenescence have been reported, data on cell-specific immune effects are largely absent. In addition, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the "ELA immune phenotype". In this thesis, we have investigated the ELA immune phenotype on a cellular level and whether this is an indirect consequence of changes in behavior or stress reactivity. To address these questions the EpiPath cohort was established, consisting of 115 young adults with or without ELA. ELA participants had experienced separation from their parents in early childhood and were subsequently adopted, which is a standard model for ELA, whereas control participants grew up with their biological parents. At a first visit, blood samples were taken for analysis of epigenetic markers and immune parameters. A selection of the cohort underwent a standardized laboratory stress test (SLST). Endocrine, immune, and cardiovascular parameters were assessed at several time points before and after stress. At a second visit, participants underwent structural clinical interviews and filled out psychological questionnaires. We observed a higher number of activated T cells in ELA, measured by HLA-DR and CD25 expression. Neither cortisol levels nor health-risk behaviors explained the observed group differences. Besides a trend towards higher numbers of CCR4+CXCR3-CCR6+ CD4 T cells in ELA, relative numbers of immune cell subsets in circulation were similar between groups. No difference was observed in telomere length or in methylation levels of age-related CpGs in whole blood. However, we found a higher expression of senescence markers (CD57) on T cells in ELA. In addition, these cells had an increased cytolytic potential. A mediation analysis demonstrated that cytomegalovirus infection " an important driving force of immunosenescence " largely accounted for elevated CD57 expression. The psychological investigations revealed that after adoption, family conditions appeared to have been similar to the controls. However, PhD thesis MMC Elwenspoek 18 ELA participants scored higher on a depression index, chronic stress, and lower on self-esteem. Psychological, endocrine, and cardiovascular parameters significantly responded to the SLST, but were largely similar between the two groups. Only in a smaller subset of groups matched for gender, BMI, and age, the cortisol response seemed to be blunted in ELA participants. Although we found small differences in the methylation level of the GR promoter, GR sensitivity and mRNA expression levels GR as well as expression of the GR target genes FKBP5 and GILZ were similar between groups. Taken together, our data suggest an elevated state of immune activation in ELA, in which particularly T cells are affected. Furthermore, we found higher levels of T cells immunosenescence in ELA. Our data suggest that ELA may increase the risk of cytomegalovirus infection in early childhood, thereby mediating the effect of ELA on T cell specific immunosenescence. Importantly, we found no evidence of HPA dysregulation in participants exposed to ELA in the EpiPath cohort. Thus, the observed immune phenotype does not seem to be secondary to alterations in the stress system or health-risk behaviors, but rather a primary effect of early life programming on immune cells. Longitudinal studies will be necessary to further dissect cause from effect in the development of the ELA immune phenotype.
This thesis is focused on improving the knowledge on a group of threatened species, the European cave salamanders (genus Hydromantes). There are three main sections gathering studies dealing with different topics: Ecology (first part), Life traits (second part) and Monitoring methodologies (third part). First part starts with the study of the response of Hydromantes to the variation of climatic conditions, analysing 15 different localities throughout a full year (CHAPTER I; published in PEERJ in August 2015). After that, the focus moves on identify which is the operative temperature that these salamander experience, including how their body respond to variation of environmental temperature. This study was conducted using one of the most advanced tool, an infrared thermocamera, which gave the opportunity to perform detailed observation on salamanders body (CHAPTER II; published in JOURNAL OF THERMAL BIOLOGY in June 2016). In the next chapter we use the previous results to analyse the ecological niche of all eight Hydromantes species. The study mostly underlines the mismatch between macro- and microscale analysis of ecological niche, showing a weak conservatism of ecological niches within the evolution of species (CHAPTER III; unpublished manuscript). We then focus only on hybrids, which occur within the natural distribution of mainland species. Here, we analyse if the ecological niche of hybrids shows divergences from those of parental species, thus evaluating the power of hybrids adaptation (CHAPTER IV; unpublished manuscript). Considering that hybrids may represent a potential threat for parental species (in terms of genetic erosion and competition), we produced the first ecological study on an allochthonous mixed population of Hydromantes, analysing population structure, ecological requirements and diet. The interest on this particular population mostly comes by the fact that its members are coming from all three mainland Hydromantes species, and thus it may represent a potential source of new hybrids (CHAPTER V; accepted in AMPHIBIA-REPTILIA in October 2017). The focus than moves on how bioclimatic parameters affect species within their distributional range. Using as model species the microendemic H. flavus, we analyse the relationship between environmental suitability and local abundance of the species, also focusing on all intermediate dynamics which provide useful information on spatial variation of individual fitness (CHAPTER VI; submitted to SCIENTIFIC REPORTS in November 2017). The first part ends with an analysis of the interaction between Hydromantes and Batracobdella algira leeches, the only known ectoparasite for European cave salamanders. Considering that the effect of leeches on their hosts is potentially detrimental, we investigated if these ectoparasites may represent a further threat for Hydromantes (CHAPTER VII; submitted to INTERNATIONAL JOURNAL FOR PARASITOLOGY: PARASITES AND WILDLIFE in November 2017). The second part is related to the reproduction of Hydromantes. In the first study we perform analyses on the breeding behaviour of several females belonging to a single population, identifying differences and similarities occurring in cohorting females (CHAPTER VIII; published in NORTH-WESTERN JOURNAL OF ZOOLOGY in December 2015). In the second study we gather information from all Hydromantes species, analysing size and development of breeding females, and identifying a relationship between breeding time and climatic conditions (CHAPTER IX; submitted to SALAMANDRA in June 2017). In the last part of this thesis, we analyse two potential methods for monitoring Hydromantes populations. In the first study we evaluate the efficiency of the marking method involving Alpha tags (CHAPTER X; published in SALAMANDRA in October 2017). In the second study we focus on evaluating N-mixtures models as a methodology for estimating abundance in wild populations (CHAPTER XI; submitted to BIODIVERSITY & CONSERVATION in October 2017).
This thesis considers the general task of computing a partition of a set of given objects such that each set of the partition has a cardinality of at least a fixed number k. Among such kinds of partitions, which we call k-clusters, the objective is to find the k-cluster which minimises a certain cost derived from a given pairwise difference between objects which end up the same set. As a first step, this thesis introduces a general problem, denoted by (||.||,f)-k-cluster, which models the task to find a k-cluster of minimum cost given by an objective function computed with respect to specific choices for the cost functions f and ||.||. In particular this thesis considers three different choices for f and also three different choices for ||.|| which results in a total of nine different variants of the general problem. Especially with the idea to use the concept of parameterised approximation, we first investigate the role of the lower bound on the cluster cardinalities and find that k is not a suitable parameter, due to remaining NP-hardness even for the restriction to the constant 3. The reductions presented to show this hardness yield the even stronger result which states that polynomial time approximations with some constant performance ratio for any of the nine variants of (||.||,f)-k-cluster require a restriction to instances for which the pairwise distance on the objects satisfies the triangle inequality. For this restriction to what we informally refer to as metric instances, constant-factor approximation algorithms for eight of the nine variants of (||.||,f)-k-cluster are presented. While two of these algorithms yield the provably best approximation ratio (assuming P!=NP), others can only guarantee a performance which depends on the lower bound k. With the positive effect of the triangle inequality and applications to facility location in mind, we discuss the further restriction to the setting where the given objects are points in the Euclidean metric space. Considering the effect of computational hardness caused by high dimensionality of the input for other related problems (curse of dimensionality) we check if this is also the source of intractability for (||.||,f)-k-cluster. Remaining NP-hardness for restriction to small constant dimensionality however disproves this theory. We then use parameterisation to develop approximation algorithms for (||.||,f)-k-cluster without restriction to metric instances. In particular, we discuss structural parameters which reflect how much the given input differs from a metric. This idea results in parameterised approximation algorithms with parameters such as the number of conflicts (our name for pairs of objects for which the triangle inequality is violated) or the number of conflict vertices (objects involved in a conflict). The performance ratios of these parameterised approximations are in most cases identical to those of the approximations for metric instances. This shows that for most variants of (||.||,f)-k-cluster efficient and reasonable solutions are also possible for non-metric instances.
At any given moment, our senses are assaulted with a flood of information from the environment around us. We need to pick our way through all this information in order to be able to effectively respond to that what is relevant to us. In most cases we are usually able to select information relevant to our intentions from what is not relevant. However, what happens to the information that is not relevant to us? Is this irrelevant information completely ignored so that it does not affect our actions? The literature suggests that even though we mayrnignore an irrelevant stimulus, it may still interfere with our actions. One of the ways in which irrelevant stimuli can affect actions is by retrieving a response with which it was associated. An irrelevant stimulus that is presented in close temporal contiguity with a relevant stimulus can be associated with the response made to the relevant stimulus " an observation termed distractor-response binding (Rothermund, Wentura, & De Houwer, 2005). The studies presented in this work take a closer look at such distractor-response bindings, and therncircumstances in which they occur. Specifically, the study reported in chapter 6 examined whether only an exact repetition of the distractor can retrieve the response with which it was associated, or whether even similar distractors may cause retrieval. The results suggested that even repeating a similar distractor caused retrieval, albeit less than an exact repetition. In chapter 7, the existence of bindings between a distractor and a response were tested beyond arnperceptual level, to see whether they exist at an (abstract) conceptual level. Similar to perceptual repetition, distractor-based retrieval of the response was observed for the repetition of concepts. The study reported in chapter 8 of this work examined the influence of attention on the feature-response binding of irrelevant features. The results pointed towards a stronger binding effects when attention was directed towards the irrelevant feature compared to whenrnit was not. The study in chapter 9 presented here looked at the processes underlying distractor-based retrieval and distractor inhibition. The data suggest that motor processes underlie distractor-based retrieval and cognitive process underlie distractor inhibition. Finally, the findings of all four studies are also discussed in the context of learning.
Water-deficit stress, usually shortened to water- or drought stress, is one of the most critical abiotic stressors limiting plant growth, crop yield and quality concerning food production. Today, agriculture consumes about 80-90% of the global freshwater used by humans and about two thirds are used for crop irrigation. An increasing world population and a predicted rise of 1.0-2.5-°C in the annual mean global temperature as a result of climate change will further increase the demand of water in agriculture. Therefore, one of the most challenging tasks of our generation is to reduce the amount water used per unit yield to satisfy the second UN Sustainable Development Goal and to ensure global food security. Precision agriculture offers new farming methods with the goal to improve the efficiency of crop production by a sustainable use of resources. Plant responses to water stress are complex and co-occur with other environmental stresses under natural conditions. In general, water stress causes plant physiological and biochemical changes that depend on the severity and the duration of the actual plant water deficit. Stomatal closure is one of the first responses to plant water stress causing a decrease in plant transpiration and thus an increase in plant temperature. Prolonged or severe water stress leads to irreversible damage to the photosynthetic machinery and is associated with decreasing chlorophyll content and leaf structural changes (e.g., leaf rolling). Since a crop can already be irreversibly damaged by only mild water deficit, a pre-visual detection of water stress symptoms is essential to avoid yield loss. Remote sensing offers a non-destructive and spatio-temporal method for measuring numerous physiological, biochemical and structural crop characteristics at different scales and thus is one of the key technologies used in precision agriculture. With respect to the detection of plant responses to water stress, the current state-of-the-art hyperspectral remote sensing imaging techniques are based on measurements of thermal infrared emission (TIR; 8-14 -µm), visible, near- and shortwave infrared reflectance (VNIR/SWIR; 0.4-2.5 -µm), and sun-induced fluorescence (SIF; 0.69 and 0.76 -µm). It is, however, still unclear how sensitive these techniques are with respect to water stress detection. Therefore, the overall aim of this dissertation was to provide a comparative assessment of remotely sensed measures from the TIR, SIF, and VNIR/SWIR domains for their ability to detect plant responses to water stress at ground- and airborne level. The main findings of this thesis are: (i) temperature-based indices (e.g., CWSI) were most sensitive for the detection of plant water stress in comparison to reflectance-based VNIR/SWIR indices (e.g., PRI) and SIF at both, ground- and airborne level, (ii) for the first time, spectral emissivity as measured by the new hyperspectral TIR instrument could be used to detect plant water stress at ground level. Based on these findings it can be stated that hyperspectral TIR remote sensing offers great potential for the detection of plant responses to water stress at ground- and airborne level based on both TIR key variables, surface temperature and spectral emissivity. However, the large-scale application of water stress detection based on hyperspectral TIR measures in precision agriculture will be challenged by several problems: (i) missing thresholds of temperature-based indices (e.g., CWSI) for the application in irrigation scheduling, (ii) lack of current TIR satellite missions with suitable spectral and spatial resolution, (iii) lack of appropriate data processing schemes (including atmosphere correction and temperature emissivity separation) for hyperspectral TIR remote sensing at airborne- and satellite level.
Surveys are commonly tailored to produce estimates of aggregate statistics with a desired level of precision. This may lead to very small sample sizes for subpopulations of interest, defined geographically or by content, which are not incorporated into the survey design. We refer to subpopulations where the sample size is too small to provide direct estimates with adequate precision as small areas or small domains. Despite the small sample sizes, reliable small area estimates are needed for economic and political decision making. Hence, model-based estimation techniques are used which increase the effective sample size by borrowing strength from other areas to provide accurate information for small areas. The paragraph above introduced small area estimation as a field of survey statistics where two conflicting philosophies of statistical inference meet: the design-based and the model-based approach. While the first approach is well suited for the precise estimation of aggregate statistics, the latter approach furnishes reliable small area estimates. In most applications, estimates for both large and small domains based on the same sample are needed. This poses a challenge to the survey planner, as the sampling design has to reflect different and potentially conflicting requirements simultaneously. In order to enable efficient design-based estimates for large domains, the sampling design should incorporate information related to the variables of interest. This may be achieved using stratification or sampling with unequal probabilities. Many model-based small area techniques require an ignorable sampling design such that after conditioning on the covariates the variable of interest does not contain further information about the sample membership. If this condition is not fulfilled, biased model-based estimates may result, as the model which holds for the sample is different from the one valid for the population. Hence, an optimisation of the sampling design without investigating the implications for model-based approaches will not be sufficient. Analogously, disregarding the design altogether and focussing only on the model is prone to failure as well. Instead, a profound knowledge of the interplay between the sample design and statistical modelling is a prerequisite for implementing an effective small area estimation strategy. In this work, we concentrate on two approaches to address this conflict. Our first approach takes the sampling design as given and can be used after the sample has been collected. It amounts to incorporate the survey design into the small area model to avoid biases stemming from informative sampling. Thus, once a model is validated for the sample, we know that it holds for the population as well. We derive such a procedure under a lognormal mixed model, which is a popular choice when the support of the dependent variable is limited to positive values. Besides, we propose a three pillar strategy to select the additional variable accounting for the design, based on a graphical examination of the relationship, a comparison of the predictive accuracy of the choices and a check regarding the normality assumptions.rnrnOur second approach to deal with the conflict is based on the notion that the design should allow applying a wide variety of analyses using the sample data. Thus, if the use of model-based estimation strategies can be anticipated before the sample is drawn, this should be reflected in the design. The same applies for the estimation of national statistics using design-based approaches. Therefore, we propose to construct the design such that the sampling mechanism is non-informative but allows for precise design-based estimates at an aggregate level.
In this thesis, we present a new approach for estimating the effects of wind turbines for a local bat population. We build an individual based model (IBM) which simulates the movement behaviour of every single bat of the population with its own preferences, foraging behaviour and other species characteristics. This behaviour is normalized by a Monte-Carlo simulation which gives us the average behaviour of the population. The result is an occurrence map of the considered habitat which tells us how often the bat and therefore the considered bat population frequent every region of this habitat. Hence, it is possible to estimate the crossing rate of the position of an existing or potential wind turbine. We compare this individual based approach with a partial differential equation based method. This second approach produces a lower computational effort but, unfortunately, we lose information about the movement trajectories at the same time. Additionally, the PDE based model only gives us a density profile. Hence, we lose the information how often each bat crosses special points in the habitat in one night. In a next step we predict the average number of fatalities for each wind turbine in the habitat, depending on the type of the wind turbine and the behaviour of the considered bat species. This gives us the extra mortality caused by the wind turbines for the local population. This value is used for a population model and finally we can calculate whether the population still grows or if there already is a decline in population size which leads to the extinction of the population. Using the combination of all these models, we are able to evaluate the conflict of wind turbines and bats and to predict the result of this conflict. Furthermore, it is possible to find better positions for wind turbines such that the local bat population has a better chance to survive. Since bats tend to move in swarm formations under certain circumstances, we introduce swarm simulation using partial integro-differential equations. Thereby, we have a closer look at existence and uniqueness properties of solutions.