Recognizing and optimizing flight opportunities with hardware and life sciences limitations

The availability of orbital space flight opportunities to conduct life sciences research has been limited. It is possible to use parabolic flight and sounding rocket programs to conduct some kinds of experiments during short episodes (seconds to minutes) of reduced gravity, but there are constraints and limitations to these programs. Orbital flight opportunities are major undertakings, and the potential science achievable is often a function of the flight hardware available. A variety of generic types of flight hardware have been developed and tested, and show great promise for use during NSTS flights. One such payload configuration is described which has already flown.     

Recognizing molecules with drug-like properties.

A variety of successful approaches to the problem of recognizing 'drug-like' molecules have been employed. These range from simple counting schemes such as the Lipinski 'rule of five' to the analysis of the multidimensional 'chemistry space' occupied by drugs, to neural network learning systems. With this variety of tools, it now appears possible to design libraries that are enriched in compounds which have desirable or 'drug-like' properties. Verifying the robustness of these methods, and extending them, will form the basis of research in this field during the next few years.     

Recognizing and reporting adverse drug reactions.

Although physicians in practice are most likely to see patients with adverse drug reactions, they may fail to recognize an adverse effect or to attribute it to a drug effect and, when recognized, they may fail to report serious reactions to the US Food and Drug Administration (FDA). To recognize and attribute an adverse event to a drug effect, physicians should review the patient''s clinical course, looking at patient risk factors, the known adverse reactions to the suspected drug, and the likelihood of a causal relationship between the drug and the adverse event-based on the temporal relationship, response to stopping or restarting the drug, and whether other factors could explain the reaction. Once an adverse drug reaction has been identified, the patient should be informed and appropriate documentation made in the patient''s medical record. Serious known reactions and all reactions to newly released drugs or those not previously known to occur (even if the certainty is low) should be reported to the FDA.     

Recognizing DNA

It has become clear that there is no simple 'code' for protein-DNA recognition and that selecting an optimal binding sequence along the DNA double helix corresponds to more than simply forming a set of specific hydrogen bonds or steric interactions. However, it has been difficult to characterize the so-called indirect components of recognition. While DNA deformation certainly underlies indirect recognition, it is not easy to determine how local fine structure and deformability depend on base sequence or exactly what percentage of recognition should be attributed to such factors. Molecular modelling can help to develop these ideas into a quantitative model, provided the calculations can be carried out fast enough to enable a comprehensive survey of base-sequence effects. I present here some recent results from our group and their consequences for improving our understanding of protein-DNA binding, and their potential for predicting, and eventually modulating, protein-DNA binding.     

Recognizing faces

Face recognition is an area where research has increased considerably in recent years, yet theoretical progress has been slow. Here it is argued that by considering the perception and recognition of familiar faces, as well as episodic memory for unfamiliar faces, a functional framework for face recognition can be developed. Experiments using faces, that include tasks analogous to 'visual search' and 'lexical decision' are described, and the processes in operation are compared with those occurring in word recognition. The results allow us to distinguish a number of possible subcomponents for a functional model of face recognition.     

Physico-chemical limitations in experimental investigations.

An element or compound in a natural water system is usually distributed between a variety of physico-chemical forms, both dissolved and particulate. The distribution is determined by the properties of the ion or molecule in question and by a number of major variables, including ionic strength, the nature and concentrations of major dissolved elements, particulate matter and organic complexing material, pH and the electron activity (pE); it may thus vary widely between different environments. The design of experiments to study sublethal effects of pollutants in sea water ideally requires that the test medium is closely matched to the environment for which information is needed, with respect to the ranges of concentration and activity, and the chemical speciation, of the pollutant and of any other constituents which may influence its effects. This in turn requires either that the pollutant can be added in the appropriate forms, implying a knowledge of the existing speciation, or that the added material rapidly exchanges with the forms already present. The implications of these requirements are most apparent for those pollutants that show complex chemical behaviour in sea water. This account concentrates on metals of toxicological significance. Consideration of particulate associations, redox speciation, and complex formation in the dissolved state with inorganic and organic ligands, suggests that physicochemical factors limit the usefulness, in terms of environmental predictions, of experimental studies of biological effects of metals, both inherently and through inadequate knowledge of environmental speciation and the mechanisms and rates of interconversion between species. Of particular importance are non-equilibrium features in speciation, such as the presence of thermodynamically unstable oxidation states and of kinetically non-labile associations. Interpretation of the nature of these associations is complicated by the presence of colloidal and organic macromolecular material in dissolved fractions as conventionally defined. While the chemical behaviour of some substances in sea water is considerably less complicated than that of the trace metals, there is a need with all types of pollutants for greater attention to physico-chemical factors in both the design and interpretation of experiments to investigate biological effects.