ARISTOTELES: A European approach for an Earth gravity field recovery mission

Under contract of the European Space Agency a system study for a spaceborne gravity field recovery mission was performed, covering as a secondary mission objective geodetic point positioning in the cm range as well. It was demonstrated that under the given programmatic constraints including dual launch and a very tight development schedule, a six months gravity field mission in a 200 km near polar, dawn-dusk orbit is adequate to determine gravity anomalies to better than 5 mgal with a spatial resolution of 100 x 100 km half wavelength. This will enable scientists to determine improved spherical harmonic coefficients of the Earth gravity field equation to the order and degree of 180 or better

Stress and eating behavior

How stress, the stress response, and the adaptation of the stress response influence our eating behavior is a central question in brain research and medicine. In this report, we highlight recent advances showing the close links between eating behavior, the stress system, and neurometabolism

Longterm existence of solutions of a reaction diffusion system with non-local terms modeling an immune response

This paper shows the global existence and boundedness of solutions of a reaction diffusion system modeling liver infections. Non-local effects in the dynamics between the virus and the cells of the immune system lead to an integro-partial differential equation with homogeneous Neumann boundary conditions. Depending on the chosen model parameters, the system shows two types of solutions which are interpreted as different infection courses. Apart from solutions decaying to zero, there are solutions with a tendency towards a stationary and spatially inhomogeneous state. By proving the boundedness of the solution in the $L^1(\Omega)$- and the $L^2(\Omega)$-norms, it is possible to show the global boundedness of the solution. The proof uses the opposite mechanisms in the reaction terms. The gained rough estimates for showing the boundedness in the $L^1(\Omega)$- and the $L^2(\Omega)$-norms are compared numerically with the norms of the solutions.Comment: 19 pages, 7 figure

Total Syntheses of (+)-Ricinelaidic Acid Lactone and of (−)-Gloeosporone Based on Transition-Metal-Catalyzed C−C Bond Formations

Total syntheses of the macrolides (R)-(+)-ricinelaidic acid lactone (6) and (−)-gloeosporone (7), a fungal germination self-inhibitor, are presented, which are distinctly shorter and more efficient than any of the previous approaches to these targets reported in the literature. Both of them benefit from the remarkable ease of macrocyclization of 1,ω-dienes by means of ring-closing olefin metathesis (RCM) using the ruthenium carbene 1a as catalyst precursor. The diene substrates are readily formed via the enantioselective addition of dialkylzinc reagents to aldehydes in the presence of catalytic amounts of Ti(OiPr)4 and bis-triflamide 18 and/or the stereoselective allylation of aldehydes developed by Keck et al. using allyltributylstannane in combination with a catalyst formed from Ti(OiPr)4 and (S)-(−)-1,1‘-bi-2-naphthol. Comparative studies show this latter procedure to be more practical than the stoichiometric allylation reaction employing the allyltitanium−α,α,α‘,α‘-tetraaryl-1,3-dioxolane-4,5-dimethanol complex 3b. Finally, a method for the efficient ring closure of 4-pentenoic acid esters by RCM is presented that relies on the joint use of 1a and Ti(OiPr)4 as a binary catalyst system. These results not only expand the scope of RCM to previously unreactive substrates but also provide additional evidence for the important role of ligation of the evolving ruthenium carbene center to a polar relay substituent on the substrate which constitutes the necessary internal bias for the RCM-based macrocyclization process

Build-Ups in the Supply Chain of the Brain: on the Neuroenergetic Cause of Obesity and Type 2 Diabetes Mellitus

Obesity and type 2 diabetes have become the major health problems in many industrialized countries. A few theoretical frameworks have been set up to derive the possible determinative cause of obesity. One concept views that food availability determines food intake, i.e. that obesity is the result of an external energy “push” into the body. Another one views that the energy milieu within the human organism determines food intake, i.e. that obesity is due to an excessive “pull” from inside the organism. Here we present the unconventional concept that a healthy organism is maintained by a “competent brain-pull” which serves systemic homeostasis, and that the underlying cause of obesity is “incompetent brain-pull”, i.e. that the brain is unable to properly demand glucose from the body. We describe the energy fluxes from the environment, through the body, towards the brain with a mathematical “supply chain” model and test whether its predictions fit medical and experimental data sets from our and other research groups. In this way, we show data-based support of our hypothesis, which states that under conditions of food abundance incompetent brain-pull will lead to build-ups in the supply chain culminating in obesity and type 2 diabetes. In the same way, we demonstrate support of the related hypothesis, which states that under conditions of food deprivation a competent brain-pull mechanism is indispensable for the continuance of the brain´s high energy level. In conclusion, we took the viewpoint of integrative physiology and provided evidence for the necessity of brain-pull mechanisms for the benefit of health. Along these lines, our work supports recent molecular findings from the field of neuroenergetics and continues the work on the “Selfish Brain” theory dealing with the maintenance of the cerebral and peripheral energy homeostasis

Model for metabolic resistance against ALS inhibitors

Due to herbicide selection pressure metabolic resistance has evolved in many weed species. In this paper we analyse the interaction between the branched chain amino acid (BBC) pathway and detoxifying pathways for herbicide breakdown. The four phase detoxification pathway of herbicides comprising the action of P450, GST, glycosyltransferase and ABC transporter is modelled by a system of coupled enzyme kinetic reactions represented by nonlinear differential equations. The herbicide under consideration inhibits the enzyme ALS, which is the key enzyme for the biosynthesis of branched amino acids. For the kinetics of ALS a Monod approach is employed with a binding site for the inhibitor. Synthetic and detoxification pathways are coupled. The model is used to study the production of branched amino acids under the action of ALS inhibitors for different structures and modes of action of the detoxification pathway. The model is capable of generating typical dose response curves and their shift in dependence of the activity pattern of the enzymes of the detoxification pathway of the inhibitor.Keywords: ALS inhibitor, branched chain amino acid biosynthesis, enzyme kinetics, metabolic resistance, metabolic networkEin Modell für die metabolische Resistenz gegen ALS InhibitorenZusammenfassung Metabolische Resistenz beinhaltet die Fähigkeit eines Organismus, toxische Substanzen abzubauen, was zu einer Verschiebung von Dosis-Wirkungskurven führt. In diesem Beitrag wird die Dynamik des Zusammenspiels der Biosynthese der verzweigtkettigen Aminosäuren mit dem Abbauweg für einen ALS Inhibitor anhand eines mathematischen Modelles untersucht. Dieses besteht aus einem System von gekoppelten enzymatischen Reaktionen, dargestellt durch nichtlineare Differentialgleichungen. Die ALS Kinetik wird durch einen Monod Ansatz beschrieben mit Pyruvat als Substrat und einer Bindungsstelle für einen nichtkompetitiven Inhibitor. Das Modell liefert typische Dosis Wirkungskurven und die Verschiebung des ED50-Wertes zu höheren Dosen in Abhängigkeit vom Aktivitätsmuster des Abbauweges für den Inhibitor. Stichwörter: ALS Inhibitor, Biosynthese von Aminosäuren, Enzymkinetik, metabolische Netzwerke, metabolische Resisten

A discrete evolutionary genetic model for the emergence of metabolic resistance

Metabolic resistance refers to the biochemical processes within the plant that degrade herbicides to less toxic compounds, resulting in a shift of the dose-response curve. A multi allelic fitness model is used to simulate the emergence of metabolic resistance. A diploid population with a single resistance locus is considered with K number of alleles. The joint evolutionary dynamics model as described by HUILLET and MARTINEZ (2011) is applied to the dynamics of metabolic resistance. This is achieved by relating the fitness parameters to the form of the dose response curve which is characterized by a steepness and a threshold parameter (ED50 value). It is assumed that the threshold parameter of individuals in a population is log-normally distributed as the result of normal genetic variation. This means that there are only very few individuals with a high degree of metabolic resistance (high threshold parameter) in a weed population if no herbicides are applied. Under the long term application of only herbicide with one mode of action, the model produces the gradual shift of the mean dose response curve of the model weed population as frequently observed in the field. The model is used to understand the dynamics of the development of metabolic resistance under field conditions.Keywords: Evolution, genetic model, metabolic resistance, multi-allelic fitness modelEin zeitdiskretes genetisches Modell für die Entwicklung metabolischer ResistenzMetabolische Resistenz ist die Fähigkeit eines Organismus, toxische Substanzen abzubauen, was zu einer Verschiebung von Dosis-Wirkungskurven (ED50-Werte) führt. Ein generelles genetisches Modell (HUILLET und MARTINEZ, 2011) für eine diploide Population mit einem einzelnen Resistsnz-Lokus und K Allelen wurde auf das Auftreten von metabolischer Resistenz angewendet. Dazu wurden die Fitnesskoeffizienten mit einer Dosiswirkungskurve verknüpft. Die Form der Kurve ist durch einen Schwellenwert (ED50-Wert) und einen Formparameter für die Steigung bestimmt. Jedes Allel Ai trägt zur Expression von einem bestimmen Schwellenwert innerhalb des Individuums bei. Es wird angenommen, dass der Schwellenwert in einer unbehandelten Population logarithmisch normalverteilt ist, d.h. die Frequenz von Individuen mit hohen ED50-Werten ist äußerst gering. Das Modell liefert die Verschiebung der Dosiswirkungskurve einer Population unter der kontinuierlichen Anwendung von Herbiziden mit dem gleichen Wirkungsmechanismus und wird dazu verwendet, Managementverfahren zur Verzögerung des Auftretens der metabolischen Resistenz zu bewerten.Stichwörter: Evolution, genetisches Modell, metabolische Resistenz, Resistenzmanagemen

The Selfish Brain: Stress and Eating Behavior

The brain occupies a special hierarchical position in human energy metabolism. If cerebral homeostasis is threatened, the brain behaves in a “selfish” manner by competing for energy resources with the body. Here we present a logistic approach, which is based on the principles of supply and demand known from economics. In this “cerebral supply chain” model, the brain constitutes the final consumer. In order to illustrate the operating mode of the cerebral supply chain, we take experimental data which allow assessing the supply, demand and need of the brain under conditions of psychosocial stress. The experimental results show that the brain under conditions of psychosocial stress actively demands energy from the body, in order to cover its increased energy needs. The data demonstrate that the stressed brain uses a mechanism referred to as “cerebral insulin suppression” to limit glucose fluxes into peripheral tissue (muscle, fat) and to enhance cerebral glucose supply. Furthermore psychosocial stress elicits a marked increase in eating behavior in the post-stress phase. Subjects ingested more carbohydrates without any preference for sweet ingredients. These experimentally observed changes of cerebral demand, supply and need are integrated into a logistic framework describing the supply chain of the selfish brain

Total Ponderomotive Force on an Extended Test Body

Droplets on insulating material suffer a nonvanishing total ponderomotive force because of the inhomogeneity of the surrounding electric field. A series expansion of this total force is proven in a two-dimensional setting by determining the line charge density at the boundary of the test body via a Fredholm integral equation, which is solved by Fourier techniques. The influence of electric charges in the neighborhood of the test body can be estimated as well as the convergence speed of the series expansion. In all realistic applications the series converges very fast. The numerical effort in the simulation of the motion of rainwater droplets on outdoor insulators reduces considerably