Making connections—strategies for single molecule fluorescence biophysics

Fluorescence spectroscopy and fluorescence microscopy carried out on the single molecule level are elegant methods to decipher complex biological systems; it can provide a wealth of information that frequently is obscured in the averaging of ensemble measurements. Fluorescence can be used to localise a molecule, study its binding with interaction partners and ligands, or to follow conformational changes in large multicomponent systems. Efficient labelling of proteins and nucleic acids is very important for any fluorescence method, and equally the development of novel fluorophores has been crucial in making biomolecules amenable to single molecule fluorescence methods. In this paper we review novel coupling strategies that permit site-specific and efficient labelling of proteins. Furthermore, we will discuss progressive single molecule approaches that allow the detection of individual molecules and biomolecular complexes even directly isolated from cellular extracts at much higher and much lower concentrations than has been possible so far

Same same but different: the evolution of TBP in archaea and their eukaryotic offspring

Transcription factors TBP and TF(II)B assemble with RNA polymerase and the promoter DNA forming the initiation complex. Despite a high degree of conservation, the molecular binding mechanisms of archaeal and eukaryotic TBP and TF(II)B differ significantly. Based on recent biophysical data, we speculate how the mechanisms co-evolved with transcription regulation and TBP multiplicity

History, background, concepts and current use of comedication and polypharmacy in psychiatry

Based on a careful literature search a review is presented of the history, background, concepts and current use of comedication and polypharmacy in psychiatry. The pros and cons of comedication and polypharmacy are presented, as well as their apparent increase in recent times. Possible reasons for the increase of comedication/polypharmacy are described. Both the potential advantages as well as the potential risks are discussed. The one sided view that all comedication/polypharmacy is nothing but problematic is questioned. Comedication/polypharmacy seems to be, among others, the current answer to the well-known limited efficacy and effectiveness of current monotherapy treatment strategies

Integrated Structure and Semantics for Reo Connectors and Petri Nets

In this paper, we present an integrated structural and behavioral model of Reo connectors and Petri nets, allowing a direct comparison of the two concurrency models. For this purpose, we introduce a notion of connectors which consist of a number of interconnected, user-defined primitives with fixed behavior. While the structure of connectors resembles hypergraphs, their semantics is given in terms of so-called port automata. We define both models in a categorical setting where composition operations can be elegantly defined and integrated. Specifically, we formalize structural gluings of connectors as pushouts, and joins of port automata as pullbacks. We then define a semantical functor from the connector to the port automata category which preserves this composition. We further show how to encode Reo connectors and Petri nets into this model and indicate applications to dynamic reconfigurations modeled using double pushout graph transformation

Opportunities for coppice management at the landscape level: the Italian experience

Coppice silviculture has a long tradition in Italy. Societal demands have led to the development of forest management techniques for integrating wood production with other kinds of forest uses and regulations have been issued to limit forest degradation. In Italy, 35% of the national forest cover is currently managed under coppice silvicultural systems that provide 66% of the annual wood production. Fuel-wood demand is increasing and a large amount of fuelwood is currently imported in Italy. Modern coppice practices differ from those adopted in the past and may have a reduced impact on ecosystem characteristics and processes. Nevertheless, coppice silviculture has a bad reputation mostly on grounds that are beyond economic, technical and ecological rationales. Neither cessation of use nor a generalized conversion from coppice to high forest are likely to respond simultaneously to the many demands deriving from complex and articulated political and economic perspectives operating at global, European, national, regional and forest stand-level scales. Different approaches of modern silviculture to coppice successfully tested in Italy for more than a decade are illustrated. We propose to combine different options at the stand and sub-stand level, including either development without human interference or conversion to high forest, and to apply these approaches within the framework of novel forest management plans and regionally consistent administrative procedures. This bottom-up approach represents a potential solution to the socio-economic and environmental challenges affecting coppicing as a silvicultural system

Coordination via Interaction Constraints I: Local Logic

Wegner describes coordination as constrained interaction. We take this approach literally and define a coordination model based on interaction constraints and partial, iterative and interactive constraint satisfaction. Our model captures behaviour described in terms of synchronisation and data flow constraints, plus various modes of interaction with the outside world provided by external constraint symbols, on-the-fly constraint generation, and coordination variables. Underlying our approach is an engine performing (partial) constraint satisfaction of the sets of constraints. Our model extends previous work on three counts: firstly, a more advanced notion of external interaction is offered; secondly, our approach enables local satisfaction of constraints with appropriate partial solutions, avoiding global synchronisation over the entire constraints set; and, as a consequence, constraint satisfaction can finally occur concurrently, and multiple parts of a set of constraints can be solved and interact with the outside world in an asynchronous manner, unless synchronisation is required by the constraints. This paper describes the underlying logic, which enables a notion of local solution, and relates this logic to the more global approach of our previous work based on classical logic

Experimental validation of a self-calibrating cryogenic mass flowmeter

The Karlsruhe Institute of Technology (KIT) and the WEKA AG jointly develop a commercial flowmeter for application in helium cryostats. The flowmeter functions according to a new thermal measurement principle that eliminates all systematic uncertainties and enables self-calibration during real operation. Ideally, the resulting uncertainty of the measured flow rate is only dependent on signal noises, which are typically very small with regard to the measured value. Under real operating conditions, cryoplant-dependent flow rate fluctuations induce an additional uncertainty, which follows from the sensitivity of the method. This paper presents experimental results with helium at temperatures between 30 and 70 K and flow rates in the range of 4 to 12 g/s. The experiments were carried out in a control cryostat of the 2 kW helium refrigerator of the TOSKA test facility at KIT. Inside the cryostat, the new flowmeter was installed in series with a Venturi tube that was used for reference measurements. The measurement results demonstrate the self-calibration capability during real cryoplant operation. The influences of temperature and flow rate fluctuations on the self-calibration uncertainty are discussed

History-sensitive versus future-sensitive approaches to security in distributed systems

We consider the use of aspect-oriented techniques as a flexible way to deal with security policies in distributed systems. Recent work suggests to use aspects for analysing the future behaviour of programs and to make access control decisions based on this; this gives the flavour of dealing with information flow rather than mere access control. We show in this paper that it is beneficial to augment this approach with history-based components as is the traditional approach in reference monitor-based approaches to mandatory access control. Our developments are performed in an aspect-oriented coordination language aiming to describe the Bell-LaPadula policy as elegantly as possible. Furthermore, the resulting language has the capability of combining both history- and future-sensitive policies, providing even more flexibility and power.Comment: In Proceedings ICE 2010, arXiv:1010.530

Choreographies with Secure Boxes and Compromised Principals

We equip choreography-level session descriptions with a simple abstraction of a security infrastructure. Message components may be enclosed within (possibly nested) "boxes" annotated with the intended source and destination of those components. The boxes are to be implemented with cryptography. Strand spaces provide a semantics for these choreographies, in which some roles may be played by compromised principals. A skeleton is a partially ordered structure containing local behaviors (strands) executed by regular (non-compromised) principals. A skeleton is realized if it contains enough regular strands so that it could actually occur, in combination with any possible activity of compromised principals. It is delivery guaranteed (DG) realized if, in addition, every message transmitted to a regular participant is also delivered. We define a novel transition system on skeletons, in which the steps add regular strands. These steps solve tests, i.e. parts of the skeleton that could not occur without additional regular behavior. We prove three main results about the transition system. First, each minimal DG realized skeleton is reachable, using the transition system, from any skeleton it embeds. Second, if no step is possible from a skeleton A, then A is DG realized. Finally, if a DG realized B is accessible from A, then B is minimal. Thus, the transition system provides a systematic way to construct the possible behaviors of the choreography, in the presence of compromised principals