Re-face stereospecificity of methylenetetrahydromethanopterin and methylenetetrahydrofolate dehydrogenases is predetermined by intrinsic properties of the substrate

Four different dehydrogenases are known that catalyse the reversible dehydrogenation of N5,N10-methylenetetrahydromethanopterin (methylene-H4MPT) or N5,N10-methylenetetrahydrofolate (methylene-H4F) to the respective N5,N10-methenyl compounds. Sequence comparison indicates that the four enzymes are phylogenetically unrelated. They all catalyse the Re-face-stereospecific removal of the pro-R hydrogen atom of the coenzyme's methylene group. The Re-face stereospecificity is in contrast to the finding that in solution the pro-S hydrogen atom of methylene-H4MPT and of methylene-H4F is more reactive to heterolytic cleavage. For a better understanding we determined the conformations of methylene-H4MPT in solution and when enzyme-bound by using NMR spectroscopy and semiempirical quantum mechanical calculations. For the conformation free in solution we find an envelope conformation for the imidazolidine ring, with the flap at N10. The methylene pro-S C-H bond is anticlinal and the methylene pro-R C-H bond is synclinal to the lone electron pair of N10. Semiempirical quantum mechanical calculations of heats of formation of methylene-H4MPT and methylene-H4F indicate that changing this conformation into an activated one in which the pro-S C-H bond is antiperiplanar, resulting in the preformation of the leaving hydride, would require a deltadeltaH(f) of +53 kJ mol-1 for methylene-H4MPT and of +51 kJ mol-1 for methylene-H4F. This is almost twice the energy required to force the imidazolidine ring in the enzyme-bound conformation of methylene-H4MPT (+29 kJ mol-1) or of methylene-H4F (+35 kJ mol-1) into an activated conformation in which the pro-R hydrogen atom is antiperiplanar to the lone electron pair of N10. The much lower energy for pro-R hydrogen activation thus probably predetermines the Re-face stereospecificity of the four dehydrogenases. Results are also presented explaining why the chemical reduction of methenyl-H4MPT+ and methenyl-H4F+ with NaBD4 proceeds Si-face-specific, in contrast to the enzyme-catalysed reaction.     

Numerical studies of Jökulhlaups

The aim of this paper is to investigate Jökulhlaups: outbursts of ice-dammed lakes. The governing equations of unsteady water flow through straight, circular conduits, as derived by the authors in a previous paper, are compared with the equations of Nye, and for the steady state situation with Röthlisberger's theory. The dynamic theory is treated numerically by a finite-difference technique. Run-off simulations are illustrated for a model of the Grimsvötn Jökulhlaup, a periodic outburst of a subglacial lake beneath the Vatnajökull in Iceland. We study how various parameters, such as the friction coefficient of the conduit, and constants in the flow law of ice, influence the evolution of the outburst. In particular, we compute discharge hydrographs both incorporating and neglecting the rate of change of internal energy. It is shown that this term is not negligible and that the lake temperature, as a boundary condition, strongly influences the time-discharge relation and might explain the abrupt end of the outburst well before the lake has been emptied.     

Complex genetic predisposition to cancer in an extended HNPCC family with an ancestral hMLH1 mutation

Hereditary non-polyposis colorectal cancer (HNPCC) is characterised by a genetic predisposition to develop colorectal cancer at an early age and, to a lesser degree, cancer of the endometrium, ovaries, urinary tract, and organs of the gastrointestinal tract other than the colon. In the majority of families the disease is linked to mutations in one of the two mismatch repair genes, hMSH2 or hMLH1. We have found a novel hMLH1 nonsense mutation in a Swiss family with Lynch syndrome, which has been transmitted through at least nine generations. A different tumour spectrum of neoplasms of the skin, soft palate, breast, duodenum, and pancreas was observed in three branches of this family, where there was a virtual absence of colonic tumours. The hMLH1 mutation could not be detected in members of these branches suggesting that at least a second genetic defect predisposing to cancer is segregating in part of the kindred.     

Wave propagation and attenuation in paramagnetic and soft ferromagnetic materials

Magneto-elastic wave propagation for para- and soft ferromagnetic materials is discussed, both analytically and numerically. The basic theory used is the one of Hutter and Pao[20]. While the analytic results are not essentially different from those derived by others, the numerical calculations allowed for the first time the calculation of wave attenuation as a function of the wave length, electrical conductivity, magnetizability and intensity and direction of the magnetic induction B. Furthermore some “unusual” behavior was numerically detected for very large B fields and the conditions are described under which this behavior should experimentally be tested.     

Exploring selfish reinforcement learning in repeated games with stochastic rewards

In this paper we introduce a new multi-agent reinforcement learning algorithm, called exploring selfish reinforcement learning (ESRL). ESRL allows agents to reach optimal solutions in repeated non-zero sum games with stochastic rewards, by using coordinated exploration. First, two ESRL algorithms for respectively common interest and conflicting interest games are presented. Both ESRL algorithms are based on the same idea, i.e. an agent explores by temporarily excluding some of the local actions from its private action space, to give the team of agents the opportunity to look for better solutions in a reduced joint action space. In a latter stage these two algorithms are transformed into one generic algorithm which does not assume that the type of the game is known in advance. ESRL is able to find the Pareto optimal solution in common interest games without communication. In conflicting interest games ESRL only needs limited communication to learn a fair periodical policy, resulting in a good overall policy. Important to know is that ESRL agents are independent in the sense that they only use their own action choices and rewards to base their decisions on, that ESRL agents are flexible in learning different solution concepts and they can handle both stochastic, possible delayed rewards and asynchronous action selection. A real-life experiment, i.e. adaptive load-balancing of parallel applications is added.     

Universal Intelligence: A Definition of Machine Intelligence

A fundamental problem in artificial intelligence is that nobody really knows what intelligence is. The problem is especially acute when we need to consider artificial systems which are significantly different to humans. In this paper we approach this problem in the following way: we take a number of well known informal definitions of human intelligence that have been given by experts, and extract their essential features. These are then mathematically formalised to produce a general measure of intelligence for arbitrary machines. We believe that this equation formally captures the concept of machine intelligence in the broadest reasonable sense. We then show how this formal definition is related to the theory of universal optimal learning agents. Finally, we survey the many other tests and definitions of intelligence that have been proposed for machines.     

Application of a real-world university-course timetabling model solved by integer programming

In this case study, we describe an integer programming (IP) approach, which has been implemented at the School of Economics and Management at Hannover University, Germany, to create the complete timetable of all courses for a term. Approximately 150 different weekly lectures, tutorials and seminars ranging from 5 to 650 students are taught by about 100 teachers. The decision problem is to assign these teaching groups to time slots and rooms so that several soft and hard constraints are met. It is modeled as an assignment problem with numerous types of constraints and about 100,000 binary or integer variables. An open source mixed-integer solver can be used to solve the problem to optimality within minutes whereas the commercial CPLEX solver takes only seconds. We also describe the implementation process and report results from an anonymous satisfaction survey among the faculty with respect to the new planning approach.     

The MPEG-4 Multimedia Coding Standard: Algorithms, Architectures and Applications

The upcoming MPEG-4 standard provides new possibilities for the compression and presentation of multimedia contents. The main characteristics of MPEG-4 are the object-based coding and representation of an audio-visual scene and the ability to code objects of natural or synthetic origin. These features will enhance existing applications with new functionalities and enable standardised solutions for new applications. This paper provides an overview of the three major parts Systems, Visual and Audio of the new MPEG-4 standard, highlights implementation aspects for some envisaged types of MPEG-4 terminals and describes possible future multimedia application scenarios using MPEG-4 functionalities.     

Simulation and Experiment of the Homogeneously Catalyzed Production of Terpenyl Amine

Continuous terpenyl amine production via a homogeneously catalyzed hydroamination is presented. For the recycling of the catalyst a liquid‐liquid system combined with a subsequent acid complexation as capturing step for the terpenyl amine was used. The whole process was run in pilot plant scale. At first, batch experiments were conducted to determine reaction equilibria of the hydroamination and the acid complexation. On this, a process model was developed which is based on equilibrium stages. This process model was validated by running the continuous process and was able to predict the continuous process in good agreement with experimental data. So, it allows a reduction of the experimental effort.     

Poly(lauryl acrylate) and poly(stearyl acrylate) grafted multiwalled carbon nanotubes for polypropylene composites

Two new polymer grafts on an industrial grade multiwalled carbon nanotube (MWCNT) were prepared through a non-oxidative pathway employing controlled free radical polymerization for surface initiated polymer grafting. After photochemical introduction of an ATRP initiator onto the MWCNT, polymerizations of lauryl or stearyl acrylate were performed, resulting in two novel polymer modifications on the MWCNT (poly(lauryl acrylate) or poly(stearyl acrylate)). The method was found to give time dependent loading of polymers as a function of time (up to 38 wt% for both acrylates), and showed a plateau in loading after 12 h of polymerization. The modified nanomaterials were melt mixed into polypropylene composites with very low filler loading (0.3 wt%), whereafter both the thermal and electrical properties were investigated by DSC and dielectric resonance spectroscopy. The electrical properties were found to be substantially improved, where poly(lauryl acrylate) was found to be the superior surface modification, resulting in a conductive composite.