Cyclization and annulation reactions of nitrogen-substituted cyclopropanes and cyclobutanes.

Cyclization and annulation reactions initiated by ring-opening of small rings, especially cyclopropanes and cyclobutanes are now well-established in synthetic chemistry. Nevertheless, the potential of aminocyclopropanes and cyclobutanes, an important subclass for the synthesis of nitrogen-rich building blocks, has remained unexploited for a long time, despite important pioneering results. In the last decade, the situation has changed dramatically and new catalytic methods have emerged both for cyclization and annulation reactions. The purpose of this feature article is to present recent progress in this area, including our own work using donor-acceptor cyclopropanes and cyclobutanes.

Lagrangian Coherent Structures for Design Analysis of Revolving Doors.

Room air flow and air exchange are important aspects for the design of energy-efficient buildings. As a result, simulations are increasingly used prior to construction to achieve an energy-efficient design. We present a visual analysis of air flow generated at building entrances, which uses a combination of revolving doors and air curtains. The resulting flow pattern is challenging because of two interacting flow patterns: On the one hand, the revolving door acts as a pump, on the other hand, the air curtain creates a layer of uniformly moving warm air between the interior of the building and the revolving door. Lagrangian coherent structures (LCS), which by definition are flow barriers, are the method of choice for visualizing the separation and recirculation behavior of warm and cold air flow. The extraction of LCS is based on the finite-time Lyapunov exponent (FTLE) and makes use of a ridge definition which is consistent with the concept of weak LCS. Both FTLE computation and ridge extraction are done in a robust and efficient way by making use of the fast Fourier transform for computing scale-space derivatives.

Sketching Uncertainty into Simulations.

In a variety of application areas, the use of simulation steering in decision making is limited at best. Research focusing on this problem suggests that most user interfaces are too complex for the end user. Our goal is to let users create and investigate multiple, alternative scenarios without the need for special simulation expertise. To simplify the specification of parameters, we move from a traditional manipulation of numbers to a sketch-based input approach. Users steer both numeric parameters and parameters with a spatial correspondence by sketching a change onto the rendering. Special visualizations provide immediate visual feedback on how the sketches are transformed into boundary conditions of the simulation models. Since uncertainty with respect to many intertwined parameters plays an important role in planning, we also allow the user to intuitively setup complete value ranges, which are then automatically transformed into ensemble simulations. The interface and the underlying system were developed in collaboration with experts in the field of flood management. The real-world data they have provided has allowed us to construct scenarios used to evaluate the system. These were presented to a variety of flood response personnel, and their feedback is discussed in detail in the paper. The interface was found to be intuitive and relevant, although a certain amount of training might be necessary.

On the origin of the genetic code.

A series of stages in the evolution of the genetic code is postulated, representing a chain of logical steps that leads to the present-day code. The stages described are based on translation machinery between the RNA world and that of amino acids, a model that consists of an RNA assembler strand along which RNA hairpin molecules are lined up, forming a picket-fence-like aggregate. Each hairpin carries an amino acid at the bottom of one of its legs, and the mutual proximity of amino acids achieved in this way facilitates their linkage into oligopeptides, in a sequence governed by the nucleotide sequence along the assembler strand, the code. The order in which amino acids are introduced into the code is in the approximate order of their availability, tempered by polarity and structural considerations.

Evolution of early mechanisms of translation of genetic information into polypeptides.

In devising models of the origin of life it is necessary to tackle the problems that the processes of genetic information transfer that are central to life depend on molecules that are themselves the products of such processes--enzymes. A proposed model must eventually yield a detailed chain of processes that can be checked experimentally. We have developed a model in which interactions between the helices of hairpin-loop 'adaptor' RNA molecules (amino acid carrying), lined up side-by-side by sequence complementarity to another 'messenger' RNA, promotes polypeptide synthesis.

DNA polymerase beta from brain neurons is a repair enzyme.

DNA polymerase beta was isolated from rat cortex neurons and characterised. Its properties were strikingly similar to those of other mammalian beta-polymerases. In adult rats, this was the major DNA polymerase occurring in neuronal nuclei, which contained no alpha-polymerase, 99.2% beta-polymerase and only 0.8% gamma-polymerase. Isolated neuronal nuclei of this developmental stage were shown to perform ultraviolet-induced repair DNA synthesis in vitro. Since beta-polymerase was virtually the exclusive DNA polymerase in these nuclei it was concluded that the beta enzyme was responsible for the observed DNA repair. This was further substantiated by demonstrating a virtually complete suppression of DNA repair in irradiated nuclei by 2',3'-dideoxyribosylthymine 5'-triphosphate (d2TTP), a potent beta-polymerase inhibitor. However, the presence of minute amounts of gamma-polymerase in neuronal nuclei and its susceptibility to d2TTP did not allow one to rule out an ancillary role of DNA polymerase gamma in DNA repair. In view of the similarity of the neuronal DNA polymerase beta with all other mammalian beta-polymerases it may be speculated that the ability to perform repair DNA synthesis is not unique to the neuronal enzyme but is a general function of all beta-polymerases.