J.H. van den Berg

Anytime path planning and replanning in dynamic environments

We present an efficient, anytime method for path planning in dynamic environments. Current approaches to planning in such domains either assume that the environment is static and replan when changes are observed, or assume that the dynamics of the environment are perfectly known a priori. Our approach takes into account all prior information about both the static and dynamic elements of the environment, and efficiently updates the solution when changes to either are observed. As a result, it is well suited to robotic path planning in known or unknown environments in which there are mobile objects, agents or adversaries

Sediment Supply-Limited Bedforms in Sand-Gravel Bed Rivers

The stability of bedforms in mixtures of gravel and sand is not well understood. Two bedform types are characteristic: flow- parallel sand ribbons and flow-transverse barchans. Flume experi- ments and field data presented here show that gradual transitions exist from sand ribbons to barchans, and from barchans to fully de- veloped dunes. Barchans and sand ribbons occur when not enough transportable sediment is available for the formation of fully devel- oped ripples or dunes. The reason is that a part of the bed sediment is immobile, e.g., with an armor layer, which limits the sediment sup- ply and thus the volume of sediment available for the formation of bedforms. Bedform stability diagrams are shown to be extendable to sedi- ment supply-limited bedforms in sand-gravel sediment, if the par- ticle parameters of the diagrams are derived from the transported sediment instead of the bed sediment. Barchans and forms transi- tional to fully developed dunes plot in the dune stability fields. Sand ribbons, on the other hand, plot in the ripple, lower plane bed, and dune fields. In the case of sediment supply limitation, bedforms are partly or completely related to the characteristics of the sediment supply from upstream. The sediment underlying the bedforms may be a stable armor and the exchange of sediment between this armor and the bedforms may be small or non-existent. Consequently, bedform char- acteristics in sand-gravel mixtures in supply-limited conditions often are not predictable from the local hydraulics and sediment charac- teristics.

GMP production of pDERMATT for vaccination against melanoma in a phase I clinical trial

For the treatment of melanoma DNA vaccines are a promising therapeutic approach. In our institute a plasmid encoding a melanoma-associated epitope (MART-1) and an immunostimulatory sequence (tetanus toxin fragment-c) termed pDERMATT was developed. In a phase I study the plasmid will be administered intradermally using a newly developed tattoo strategy to assess the toxicity and efficacy of inducing tumor-specific T-cell immunity. To facilitate this study a Good Manufacturing Practice (GMP)-compliant plasmid manufacturing process was set up and a pharmaceutical dosage form was developed. Each batch resulted in approximately 200mg plasmid DNA of a high purity >90% supercoiled DNA, an A260/280 ratio 1.80-1.95, undetectable or extremely low residual endotoxins, Escherichia coli host cell protein, RNA, and DNA. In the manufacturing process no animal derived enzymes like RNase or potentially harmful organic solvents are used. After sterile filtration the concentration of the plasmid solution is approximately 1.1mg/mL. For the scheduled phase I study a concentration of 5mg/mL is desired, and further concentration of the solution is achieved by lyophilisation. The formulation solution is composed of 1mg/mL pDERMATT and 20mg/mL sucrose in Water for Injections. Upon reconstitution with a five times smaller volume an isotonic sucrose solution containing 5mg/mL pDERMATT is obtained. Lyophilised pDERMATT is sterile with >90% supercoiled DNA, an A260-280 ratio 1.80-1.95, content 90-110% of labeled, and residual water content <2% (w/w). The product yields the predicted profile upon restriction-enzyme digestion, is highly immunogenic as confirmed in an in vivo mouse model, and stable for at least six months at 5 degrees C. We have not only developed a reproducible process to manufacture pharmaceutical grade plasmid DNA but also a stable dosage form for the use in clinical trials.

Effects of spatial discretization in ice-sheet modelling using the shallow-ice approximation

This paper assesses a two-dimensional, vertically integrated ice model for its numerical properties in the calculation of ice-sheet evolution on a sloping bed using the shallow-ice approxi- mation. We discuss the influence of initial conditions and individual model parameters on the models numerical behaviour, with emphasis on varying spatial discretizations. The modelling results suffer badly from numerical problems. They show a strong dependence on gridcell size and we conclude that the widely used gridcell spacing of 20 km is too coarse. The numerical errors are small in each single time- step, but increase non-linearly over time and with volume change, as a result of feedback of the mass balance with height. We propose a new method for the calculation of the surface gradient near the margin, which improves the results significantly. Furthermore, we show that we may use dimension analysis as a tool to explain in which situations numerical problems are to be expected.

DNA tattoo vaccination: Effect on plasmid purity and transfection efficiency of different topoisoforms

Recently, DNA tattooing was introduced as novel intradermal administration technique for plasmid DNA (pDNA) vaccines. The aim of this study was to determine if tattooing affects the integrity of pDNA (reduction in supercoiled (SC) content) and whether a change in pDNA topology would affect antigen expression and immune response. We show that 1.) in vitro tattooing of pDNA solutions results in minor damage to pDNA (<or=3% SC pDNA reduction) and only open circular (OC) pDNA formation, 2.) antigen expression and T-cell responses upon tattoo administration of SC and OC pDNA are equal in a murine model, 3.) SC pDNA gives a significantly higher antigen expression than OC and linear pDNA in ex vivo human skin, 4.) pDNA topology does not influence antigen expression when formulated as PEGylated polyplexes. We conclude that a 3% reduction in SC purity most likely will have little or no effect on clinical antigen expression and T-cell responses. For intradermal tattoo administration the ex vivo skin model might be more suitable than the standard murine model for distinguishing subtle alterations in antigen expression of clinical pDNA formulations. The results from this study enable justification of release and shelf-life specifications of pDNA products applied by this specific route of administration, as requested by the regulatory authorities (>or=80% SC).

THE ROTATION OF ITALY: PRELIMINARY PALAEOMAGNETIC DATA FROM THE UMBRIAN SEQUENCE, NORTHERN APENNINES

A preliminary collection of 43 palaeomagnetic samples (10 sites) from the miogeosynclinal and supposedly autochthonous Umbrian sequence in the Northern Apennines, Italy, was analysed by means of alternating magnetic fields and thermal demagnetization studies. The older group of samples, taken from the upper part of the Calcari Diasprini (Maim), the Fucoid Marls (Albian/Cenomanian) and from the basal part of the Scaglia Bianca (Early Late Cretaceous), all showed normal polarity directions and resulted in a mean site direction: D = 290.5 ° , I = +51.5 ° , a9s = ll°,k = 74, N= 4. The younger group of samples, taken throughout the Scaglia Rossa sequence (Latest Cretaceous/Middle Eocene) showed normal and reversed polarity directions. In contrast to the older group, the magnetic analysis of these samples resulted in a considerably less dense grouping of site mean directions. This presumably is due to inaccuracies introduced with the very large bedding tilt corrections that had to be applied to the samples of some sites. A tentative mean site direction for these Scaglia Rossa samples was computed as: D = 351 ° , I = +52.5 ° , ags = 23.5 ° , k = 11.5, N=5. Despite the low precision of the Scaglia Rossa result, the significant deviation between this Latest Cretaceous/ Early Tertiary direction and the Late Jurassic/Early Late Cretaceous direction indicates a counterclockwise rotation of more than forty degrees. This rotation can be dated as Late Cretaceous. How far these data from the Northern Apennines apply to other parts of the Italian Peninsula has yet to be established. The timing of this rotation is not at variance with the data from other parts of Mediterranean Europe (Southern Alps, Iberian Peninsula) and from Africa. However, taking into account the preliminary nature of the results, the amount of rotation of the Northern Apennines seems to surpass the rotation angle which is deduced from the palaeomagnetic data for Africa.

DNA Vaccines and Intradermal Vaccination by DNA Tattooing

Over the past two decades, DNA vaccination has been developed as a method for the induction of immune responses. However, in spite of high expectations based on their efficacy in preclinical models, immunogenicity of first generation DNA vaccines in clinical trials was shown to be poor, and no DNA vaccines have yet been licensed for human use. In recent years significant progress has been made in the development of second generation DNA vaccines and DNA vaccine delivery methods. Here we review the key characteristics of DNA vaccines as compared to other vaccine platforms, and recent insights into the prerequisites for induction of immune responses by DNA vaccines will be discussed. We illustrate the development of second generation DNA vaccines with the description of DNA tattooing as a novel DNA delivery method. This technique has shown great promise both in a small animal model and in non-human primates and is currently under clinical evaluation.

Fluvial to tidal transition zone facies in the McMurray Formation (Christina River, Alberta, Canada), with emphasis on the reflection of flow intensity in bottomset architecture

An outcrop of the McMurray Formation along the Christina River (Alberta, Canada) has been investigated to better understand depositional processes and setting. The succession is formed by large-scale tabular sets of unidirectional trough cross-stratification. Many of these sets are characterized by profusely ripple-laminated and thick, laterally persistent bottomset intervals at their base. Additionally, reactivation surfaces and infrequent set climbers occur in the foresets. The bottomsets almost entirely consist of backflow cross-lamination. Available knowledge indicates that this points to a rather strong vortex circulation and related strong and persistent main flow velocity. The observed bottomset succession is discussed within the range of variation in bottomset architecture that results from the structure and strength of the flow in the wake behind dunes and related strength of the main flow. Sets descend along a gentle slope, suggesting that dunes filled a preexisting depression, thus representing conditions of a vertically expanding and decelerating flow. This means that aggradation rate was high, which is in accordance with the thickness of the preserved sets. Systematic changes in flow strength are documented by downstream cyclic variations in organic debris, bottomset thickness, and foreset dip. The periodic increase of flow velocity is interpreted as being produced by the increased strength of the river flow during the ebbing tide on the days around spring tide. Apart from these subtle variations, the area experienced large changes in flow strength due to seasonal differences in fluvial discharge. The turbidity maximum zone was located downstream of the study site since thick slackwater mud drapes that characterize the seaward part of the fluvial to tidal transition zone are not present; only a few thin mud drapes are found at the study locality. Therefore, it is concluded that deposition took place in the most landward part of this zone. This new interpretation of this facies in the Christina River area is in line with the inferred depositional setting of the transition to the overlying thick point bar units formed by inclined heterolithic stratification.

A note on percolation theory

In percolation theory the critical probability Pc(G) of an infinite connected graph G is defined as the supremum of those values of the occupation probability for which only finite clusters occur. An interesting question is the following: is each number between 0 and 1 the critical probability of some graph? It is shown that the answer is positive. A remarkable intermediate result is that for an important class of graphs the following holds: for each p>or=Pc(G) there exists a subgraph of G with critical probability equal to p.

Percolation theory on pairs of matching lattices

An important magnitude in percolation theory is the critical probability, which is defined as the supremum of those values of the occupation‐probability p, for which only finite clusters occur. In 1964 Sykes and Essam obtained the relation P(s)c(L) +P(s)c(L*) =1, where L and L* are a pair of matching lattices and P(s)c denotes the critical probability (site‐case). The proof was not complete, but based on certain assumptions about the mean number of clusters. Though Sykes and Essam suggested that the above relation holds for all mosaics (i.e., multiply‐connected planar graphs) and decorated mosaics, we have constructed a counterexample. Subsequently, for a more restricted class of graphs, an alternative derivation of the Sykes–Essam relation is given, this time based on the usual assumption that below the critical probability the mean cluster size is finite. The latter assumption is also used to prove for some nontrivial subgraphs of the simple quadratic lattice S, that their critical probability is equal ...