To combine or not to combine? issues of combining forecasts

This paper addresses issues such as: Does it always pay to combine individual forecasts of a variable? Should one combine an unbiased forecast with one that is heavily biased? Should one use optimal weights as suggested by Bates and Granger over twenty years ago? A simple model which accounts for the main features of individual forecasts is put forward. Bayesian analysis of the model using noninformative and informative prior probability densities is provided which extends and generalizes results obtained by Winkler (1981) and compared with non-Bayesian methods of combining forecasts relying explicitly on a statistical model for the individual forecasts. It is shown that in some instances it is sensible to use a simple average of individual forecasts instead of using Bates and Granger type weights. Finally, model uncertainty is considered and the issue of combining different models for individual forecasts is addressed.     

On the biomechanical function of the liver capsule

Summary We have carried out histomechanical studies on the human and bovine liver capsule under tension loading. Results: Nonlinear force-time curve under extension with constant speed, initial upper and lower summit decrease of the dynamic relaxation curve, amplitude diminution phenomenon of the dynamic relaxation in the lower nonlinear part of the extension-time curve, dynamic (cyclic) force recovery.Acknowledgments. We are grateful for helpful suggestions to Dr P. Freyer. The authors are indebted to Mrs C. Beckers and Mr W. Graulich — The experimental study was supported by the DFG (Deutsche Forschungsgemeinschaft).     

Guinea-pig adipose tissue responsiveness to catecholamines

Zusammenfassung Es wurde festgestellt, dass Meerschweinchen-Fettgewebe auf Catecholamine weniger reagierte als Rattengewebe. War die Inkubation zerkleinerten Gewebes mit Aminen langfristig, so zeigte das Meerschweinchen-Fettgewebe eine lipolytische Aktivität.     

A synthetic multicellular system for programmed pattern formation

Pattern formation is a hallmark of coordinated cell behaviour in both single and multicellular organisms. It typically involves cell-cell communication and intracellular signal processing. Here we show a synthetic multicellular system in which genetically engineered 'receiver' cells are programmed to form ring-like patterns of differentiation based on chemical gradients of an acyl-homoserine lactone (AHL) signal that is synthesized by 'sender' cells. In receiver cells, 'band-detect' gene networks respond to user-defined ranges of AHL concentrations. By fusing different fluorescent proteins as outputs of network variants, an initially undifferentiated 'lawn' of receivers is engineered to form a bullseye pattern around a sender colony. Other patterns, such as ellipses and clovers, are achieved by placing senders in different configurations. Experimental and theoretical analyses reveal which kinetic parameters most significantly affect ring development over time. Construction and study of such synthetic multicellular systems can improve our quantitative understanding of naturally occurring developmental processes and may foster applications in tissue engineering, biomaterial fabrication and biosensing.     

Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population

An RNA virus population does not consist of a single genotype; rather, it is an ensemble of related sequences, termed quasispecies. Quasispecies arise from rapid genomic evolution powered by the high mutation rate of RNA viral replication. Although a high mutation rate is dangerous for a virus because it results in nonviable individuals, it has been hypothesized that high mutation rates create a 'cloud' of potentially beneficial mutations at the population level, which afford the viral quasispecies a greater probability to evolve and adapt to new environments and challenges during infection. Mathematical models predict that viral quasispecies are not simply a collection of diverse mutants but a group of interactive variants, which together contribute to the characteristics of the population. According to this view, viral populations, rather than individual variants, are the target of evolutionary selection. Here we test this hypothesis by examining the consequences of limiting genomic diversity on viral populations. We find that poliovirus carrying a high-fidelity polymerase replicates at wild-type levels but generates less genomic diversity and is unable to adapt to adverse growth conditions. In infected animals, the reduced viral diversity leads to loss of neurotropism and an attenuated pathogenic phenotype. Notably, using chemical mutagenesis to expand quasispecies diversity of the high-fidelity virus before infection restores neurotropism and pathogenesis. Analysis of viruses isolated from brain provides direct evidence for complementation between members in the quasispecies, indicating that selection indeed occurs at the population level rather than on individual variants. Our study provides direct evidence for a fundamental prediction of the quasispecies theory and establishes a link between mutation rate, population dynamics and pathogenesis.     

Behavioural ecology: bees associate warmth with floral colour

Floral colour signals are used by pollinators as predictors of nutritional rewards, such as nectar. But as insect pollinators often need to invest energy to maintain their body temperature above the ambient temperature, floral heat might also be perceived as a reward. Here we show that bumblebees (Bombus terrestris) prefer to visit warmer flowers and that they can learn to use colour to predict floral temperature before landing. In what could be a widespread floral adaptation, plants may modulate their temperature to encourage pollinators to visit.     

SecA,a remarkable nanomachine

Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel SecYEG. SecA converts chemically stored energy in the form of ATP into a mechanical force to drive polypeptide transport through SecYEG and across the cytoplasmic membrane. In order to accommodate a translocating polypeptide chain and to release transmembrane segments of membrane proteins into the lipid bilayer, SecYEG needs to open its central channel and the lateral gate. Recent crystal structures provide a detailed insight into the rearrangements required for channel opening. Here, we review our current understanding of the mode of operation of the SecA motor protein in concert with the dynamic SecYEG channel. We conclude with a new model for SecA-mediated protein translocation that unifies previous conflicting data.