Bladder endometriosis, a remarkable resemblance in a monozygotic twin

It is known for many years that heritability plays a role in the development of endometriosis in many patients. Deep endometriosis of the bladder is a rare presentation of the disease and bladder endometriosis was not reported in monozygotic twin studies so far. Since monozygotic twins share the same genes, concordance and differences in presentation of endometriosis may help to discriminate between genetic and environmental determinants. The remarkable resemblance in the presentation of bladder endometriosis in this monozygotic twin seems to indicate that genetic factors are of importance in the arising of deep endometriosis in the bladder too

Effect analysis of transient scenarios for successful water management strategies

Recent scenario studies on water management focus on one or two projection years and the effects on the water system and functions. The future is however more complex and dynamic. Therefore, we analyse transient scenarios in order to evaluate the performance of water management strategies. Current available simulation tools are not suitable for this purpose. Therefore, we have developed and used a tool to simulate 50-100 year long time series and that is good and fast enough to simulate the effects of these scenarios and strategies on the water system and the interaction with the human system. We present the first step by means of a case study

Majorana mediated non-local charge dynamics in topological superconductors

Topology has enjoyed great success as a paradigm for the classification and understanding of condensed matter outside the framework of spontaneously broken symmetry. This success is all the more remarkable considering that the impact of interactions, in particular the Coulomb interaction between electrons, has been neglected in most analyses. Experience in topologically trivial systems demonstrates that, beyond simply leading to quantitative modifications, interactions can give rise to qualitatively new physics in condensed matter. This thesis explores the interplay between interaction effects and topologically non-trivial states and demonstrates how this interplay can lead to novel physics which is fundamentally contingent upon both a system's topological character and interactions. The prototypical example of a topological state in condensed matter is the Majorana bound state (MBS). In the work presented here, MBSs are significant because they lead to non-local fermionic states in superconductors that are bound to near-zero energy, inside the superconducting gap. The new physics arising from the synergy of MBSs and electron-electron interactions is illustrated by two examples. A Majorana-based analogue of the Kondo system is found to exhibit signs of a delocalised many-body state consisting of electrons from both metallic leads and a superconducting condensate. The presence of MBSs in a current driven capacitive Josephson junction enables excitation of the system to a non-equilibrium state and profoundly affects the overall charge dynamics of the junction. This thesis offers compelling evidence for the importance of interactions in the context of topologically non-trivial systems, not only with regard to determining the topology of the system per se, but also as the means by which new physics is realised.Funded via " EPSRC Grant No. EP/I007002/1." -- Acknowledgement

Analyzing the Functional Properties of the Creatine Kinase System with Multiscale 'Sloppy' Modeling

In this study the function of the two isoforms of creatine kinase (CK; EC 2.7.3.2) in myocardium is investigated. The ‘phosphocreatine shuttle’ hypothesis states that mitochondrial and cytosolic CK plays a pivotal role in the transport of high-energy phosphate (HEP) groups from mitochondria to myofibrils in contracting muscle. Temporal buffering of changes in ATP and ADP is another potential role of CK. With a mathematical model, we analyzed energy transport and damping of high peaks of ATP hydrolysis during the cardiac cycle. The analysis was based on multiscale data measured at the level of isolated enzymes, isolated mitochondria and on dynamic response times of oxidative phosphorylation measured at the whole heart level. Using ‘sloppy modeling’ ensemble simulations, we derived confidence intervals for predictions of the contributions by phosphocreatine (PCr) and ATP to the transfer of HEP from mitochondria to sites of ATP hydrolysis. Our calculations indicate that only 15±8% (mean±SD) of transcytosolic energy transport is carried by PCr, contradicting the PCr shuttle hypothesis. We also predicted temporal buffering capabilities of the CK isoforms protecting against high peaks of ATP hydrolysis (3750 µM*s(−1)) in myofibrils. CK inhibition by 98% in silico leads to an increase in amplitude of mitochondrial ATP synthesis pulsation from 215±23 to 566±31 µM*s(−1), while amplitudes of oscillations in cytosolic ADP concentration double from 77±11 to 146±1 µM. Our findings indicate that CK acts as a large bandwidth high-capacity temporal energy buffer maintaining cellular ATP homeostasis and reducing oscillations in mitochondrial metabolism. However, the contribution of CK to the transport of high-energy phosphate groups appears limited. Mitochondrial CK activity lowers cytosolic inorganic phosphate levels while cytosolic CK has the opposite effect

Modelling survival and connectivity of Mnemiopsis leidyi in the south-western North Sea and Scheldt estuaries

Three different models were applied to study the reproduction, survival and dispersal of Mnemiopsis leidyi in the Scheldt estuaries and the southern North Sea: a high-resolution particle tracking model with passive particles, a low-resolution particle tracking model with a reproduction model coupled to a biogeochemical model, and a dynamic energy budget (DEB) model. The results of the models, each with its strengths and weaknesses, suggest the following conceptual situation: (i) the estuaries possess enough retention capability to keep an overwintering population, and enough exchange with coastal waters of the North Sea to seed offshore populations; (ii) M. leidyi can survive in the North Sea, and be transported over considerable distances, thus facilitating connectivity between coastal embayments; (iii) under current climatic conditions, M. leidyi may not be able to reproduce in large numbers in coastal and offshore waters of the North Sea, but this may change with global warming; however, this result is subject to substantial uncertainty. Further quantitative observational work is needed on the effects of temperature, salinity and food availability on reproduction and on mortality at different life stages to improve models such as used here