Biomathematische Modellierung von Chemo- und Immuntherapie bei aggressiven Non-Hodgkin-Lymphomen

Dosis- und Zeitintensivierungen von Chemotherapie verbesserten das ereignisfreie Überleben bei Patienten mit aggressiven Non-Hodgkin-Lymphomen. Klinische Studien zeigten jedoch, dass zu starke Therapien in schlechteren Überlebensraten resultieren können. Rituximab ist ein monoklonaler Antikörper, der zu einem Durchbruch der Immuntherapie bei CD20-positiven B-Zell-Lymphomen geführt hat. Unterschiede bei den Überlebensraten zwischen einzelnen Therapievarianten werden durch Rituximab allerdings abgeschwächt. In dieser Promotionsarbeit wurde ein Modell entwickelt, welches diese Phänomene aus klinischen Studien durch die Annahme eines Anti-Tumor-Effekts des Immunsystems erklärt. Ein Differentialgleichungsmodell beschreibt die Dynamiken und Interaktionen zwischen Tumor- und Immunzellen unter Immunchemotherapie. Spezielle Parameter des Modells wurden durch Überlebenskurven aus klinischen Studien geschätzt. Dazu wurde ein Algorithmus entwickelt, der die Heterogenität der Überlebens- und Rezidivraten innerhalb eines Patientenkollektivs auf die Variabilität einiger weniger Parameter zurückführt. Das Modell wurde so an verschiedene Patientenkollektive angepasst. Schlechtere Ergebnisse bei zu intensiven Therapien werden im Modell durch eine zu starke Schädigung des Immunsystems erklärt, welches nicht mehr in der Lage ist, den residualen Tumor nach Therapieende zu bekämpfen. Ein weiterer Bestandteil des Modells ist die Vorhersage neuer Chemo- sowie Immuntherapievarianten, um vielversprechende Therapieszenarien zu ermitteln, die in die Konzeption neuer klinischen Studien einfließen können. Prognosen in Abhängigkeit von bestimmten Risikogruppen der Patienten können gestellt werden, indem Modellparameter mit messbaren Risikofaktoren assoziiert werden. Die wesentlichen Ergebnisse dieser Arbeit werden in zwei Publikationen vorgestellt

Virtual screening for PPAR-gamma ligands using the ISOAK molecular graph kernel and gaussian processes

For a virtual screening study, we introduce a combination of machine learning techniques, employing a graph kernel, Gaussian process regression and clustered cross-validation. The aim was to find ligands of peroxisome-proliferator activated receptor gamma (PPAR-y). The receptors in the PPAR family belong to the steroid-thyroid-retinoid superfamily of nuclear receptors and act as transcription factors. They play a role in the regulation of lipid and glucose metabolism in vertebrates and are linked to various human processes and diseases. For this study, we used a dataset of 176 PPAR-y agonists published by Ruecker et al. ..

Aufbau und Evaluierung eines Herz-Lungen-Maschinen-Verfahrens anhand eines Ferkelmodells

Im Rahmen dieser Arbeit sollte die günstigste Kombination der Herz-Lungen-Maschinen-Einstellparameter Blutfluss und Temperatur in Bezug auf die Kreislaufsituation und vor allem das Gehirn als ischämieempfindlichstes Organ herausgefunden werden. Als aussagekräftigster Ischämieparameter wurde in der CA1-Region des Hippocampus immunhistologisch die Expression des Reparaturenzyms Hitzeschockprotein 70 (HSP70) bestimmt. Es konnte gezeigt werden, dass die Expression von HSP70 als Maß für die ischämischen Schädigungen herangezogen werden kann. Die Hämatoxylin-Eosin gefärbten Hippocampusschnitte zeigten innerhalb des gewählten Zeitfensters von einer Stunde Ischämie und vier Stunden Reperfusion geringgradige perizelluläre Ödeme in den flussreduzierten Normothermiegruppen. Weiterhin konnte aufgezeigt werden, dass der Hirngewebeoxygenierungsindex (TOI), die Sauerstoffsättigung und das Laktat zu den intraoperativ erfassbaren Parametern zählen, an denen ein ischämischer Schaden schon frühzeitig abgeschätzt werden kann

Öko-Lebensmittel - das komplexe Zusammenspiel von Einflussfaktoren und Auswirkungen

Vorteile des Konsums ökologisch erzeugter Lebensmittel werden oft auf gesundheitliche Effekte reduziert. Ziel der Arbeit ist es, das komplexe Zusammenspiel der zahlreichen Einflussfaktoren und Auswirkungen des Konsums ökologischer Lebensmittel a ufzuzeigen. Basierend auf aktueller Literatur wurden entsprechend dem Ansatz der Ernährungsökologie mit der Modellierungstechnik NutriMod Faktoren aus den Dimensionen Gesundheit, Umwelt, Wirtschaft und Gesellschaft erfasst und in ihrer Vernetztheit dargestellt. Im resultierenden Modell können zahlreiche direkte und indirekte Zusammenhänge aufgezeigt, sowie Wirkketten und Rückkopplungen identifiziert werden, innerhalb der Dimensionen und dimensionenübergreifend. Durch die Abbildung von Mehrdimensionalität und Vernetztheit von Einflussfaktoren und Auswirkungen liefert das Modell für das kontrovers diskutierte Thema Öko-Landbau Grundlagen für weitere Forschung und für politische Entscheidungen im Sinne einer nachhaltigen Entwicklung

Cold acclimation has a differential effect on leaf vascular bundle structure and carbon export rates in natural Arabidopsis accessions originating from southern and northern Europe

Acclimation to low but non‐freezing temperature represents an ecologically important process for Arabidopsis thaliana but also for many other plant species from temperate regions. Cold acclimation comprises and affects numerous molecular and physiological processes and the maintenance of sugar supply of sink tissue by photosynthetically active source tissue is essential for plant survival. Here, changes in vascular bundle (VB) structure at the leaf petiole were analysed together with sucrose exudation rates before and after cold acclimation. Six natural Arabidopsis accessions originating from southern and northern Europe were compared. Photosynthetic efficiency, that is, maximum and effective quantum yield of photosystem II, revealed a significant effect of environmental condition. Only for northern accessions was a highly significant negative correlation observed between leaf sucrose exudation rates, xylem, and petiole cross‐sectional areas. Furthermore, only for northern accessions was a significant increase of VB and leaf petiole cross‐sectional area observed during cold acclimation. In contrast, variance of cross‐sectional areas of cold acclimated southern accessions was strongly reduced compared to control plants, while mean areas remained similar under both conditions. In summary, these findings suggest that natural Arabidopsis accessions from northern Europe significantly adjust sink strength and leaf VB structure to maintain plant growth and photosynthesis under low temperature

Mapping Submerged Aquatic Vegetation Using RapidEye Satellite Data: The Example of Lake Kummerow (Germany)

Submersed aquatic vegetation (SAV) is sensitive to changes in environmental conditions and plays an important role as a long-term indictor for the trophic state of freshwater lakes. Variations in water level height, nutrient condition, light availability and water temperature affect the growth and species composition of SAV. Detailed information about seasonal variations in littoral bottom coverage are still unknown, although these effects are expected to mask climate change-related long-term changes, as derived by snapshots of standard monitoring methods included in the European Water Framework Directive. Remote sensing offers concepts to map SAV quickly, within large areas, and at short intervals. This study analyses the potential of a semi-empirical method to map littoral bottom coverage by a multi-seasonal approach. Depth-invariant indices were calculated for four Atmospheric & Topographic Correction (ATCOR2) atmospheric corrected RapidEye data sets acquired at Lake Kummerow, Germany, between June and August 2015. RapidEye data evaluation was supported by in situ measurements of the diffuse attenuation coefficient of the water column and bottom reflectance. The processing chain was able to differentiate between SAV and sandy sediment. The successive increase of SAV coverage from June to August was correctly monitored. Comparisons with in situ and Google Earth imagery revealed medium accuracies (kappa coefficient = 0.61, overall accuracy = 72.2%). The analysed time series further revealed how water constituents and temporary surface phenomena such as sun glint or algal blooms influence the identification success of lake bottom substrates. An abundant algal bloom biased the interpretability of shallow water substrate such that a differentiation of sediments and SAV patches failed completely. Despite the documented limitations, mapping of SAV using RapidEye seems possible, even in eutrophic lakes

Do bonobos say NO by shaking their head?

Head-shaking gestures are commonly used by African great apes to solicit activities such as play. Here, we report observations of head shaking in four bonobos apparently aimed at preventing the recipient from doing something. This may reflect a primitive precursor of the negatively connoted head-shaking behavior in humans. Further investigations are needed to clarify the preventive function of head shakes and their evolutionary role in the evolution of negation in humans

Onset and early use of gestural communication in nonhuman great apes

The early gesturing of six bonobos, eight chimpanzees, three gorillas, and eight orangutans was systematically documented using focal animal sampling. Apes' were observed during their first 20 months of life in an effort to investigate: (i) the onset of gesturing; (ii) the order in which signals of different sensory modalities appear; (iii) the extent to which infants make use of these modalities in their early signaling; and (iv) the behavioral contexts where signals are employed. Orangutans differed in important gestural characteristics to African ape species. Most notably, they showed the latest gestural onset and were more likely to use their early signals in food-related interactions. Tactile and visual signals appeared similarly early across all four species. In African apes, however, visual signaling gained prominence over time while tactile signaling decreased. These findings suggest that motor ability, which encourages independence from caregivers, is an important antecedent, among others, in gestural onset and development, a finding which warrants further investigation

What Role Do Mothers Play in the Gestural Acquisition of Bonobos (Pan paniscus) and Chimpanzees (Pan troglodytes)?

Contemporary research hypothesizes that biological inheritance and ontogenetic factors shape the development of gestural communication in nonhuman great apes. However, little is known about the specific role that mothers play in the acquisition of their infants’ gestures. We observed 6 bonobo (Pan paniscus) and 4 chimpanzee (Pan troglodytes) mother–infant dyads and recorded their gesture types and frequency. We analyzed all behavioral contexts in which gestures occurred as well as the play context alone. Infants of both species were unlikely to share gestures with their mother or unrelated adult females. However, gestural sharing was prevalent within age groups. Within and across species, infant–infant and mother–mother groups were homogeneous regarding the types of gestures they shared, although there was individual variation in the frequency of gesture use. Our findings provide limited evidence that infants learned their gestures by imitating their mothers. Phylogenetic influences seem to be vital in gestural acquisition but, we suggest, repertoire development cannot be disentangled from individual social encounters during life

Eating at school. Discourses and perspectives

An die Schulverpflegung werden vielfältige (Bildungs-)Ansprüche gestellt, gleichzeitig besteht der Auftrag, Ernährungsbildung flächendeckend curricular zu verankern. Nicht zuletzt aus strukturellen Gründen stehen beide Handlungsfelder bisher kaum in Verbindung. Dieser Beitrag zum Diskurs nimmt Essen in der Schule als Bildungsfeld in den Blick. (DIPF/Orig.)School catering has to meet a wide range of (educational) demands, and at the same time, it is necessary to establish nutritional education as part of the curriculum across the board. Not least for structural reasons, the two fields of action have so far hardly been connected. This contribution to the discourse focuses on eating at school as a field of education. (DIPF/Orig.