CSM-182 - Manchester Computer Architectures, 1948 - 1975

Because of changes in computer technology and terminology, it is often difficult for present-day observers to judge the significance of early digital computer projects. In this paper we follow some architectural themes of interest, as they evolved in the design of three innovative Manchester University computers: the Mark I, Atlas and MU5. Themes such as operand address-generation, instruction formats and memory-management are traced during the period 1948-75. These themes are illustrated by a set of normalised diagrams which may act as an aid to further study of original references

CSM-180 - An SQL Interface for the IFS/2 Knowledge-Baseserver: Release 2

A version of the IFS/2, known as the IFS/Q, has been designed to give direct support to SQL programs running on a host computer. This report gives detailed specifications of one external and two internal software and firmware interfaces which have been created for IFS/Q. Release 2 differs from Release 1 mainly in the Interface B details (see section 4). We have also tidied up the IFS/Q library procedures, which are described in a companion document - (see ref 9); for convenience this is included as Appendix B to this report

The oil-dispersion bath in anthroposophic medicine – an integrative review

<p>Abstract</p> <p>Background</p> <p>Anthroposophic medicine offers a variety of treatments, among others the oil-dispersion bath, developed in the 1930s by Werner Junge. Based on the phenomenon that oil and water do not mix and on recommendations of Rudolf Steiner, Junge developed a vortex mechanism which churns water and essential oils into a fine mist. The oil-covered droplets empty into a tub, where the patient immerses for 15–30 minutes. We review the current literature on oil-dispersion baths.</p> <p>Methods</p> <p>The following databases were searched: Medline, Pubmed, Embase, AMED and CAMbase. The search terms were 'oil-dispersion bath' and 'oil bath', and their translations in German and French. An Internet search was also performed using Google Scholar, adding the search terms 'study' and 'case report' to the search terms above. Finally, we asked several experts for gray literature not listed in the above-mentioned databases. We included only articles which met the criterion of a clinical study or case report, and excluded theoretical contributions.</p> <p>Results</p> <p>Among several articles found in books, journals and other publications, we identified 1 prospective clinical study, 3 experimental studies (enrolling healthy individuals), 5 case reports, and 3 field-reports. In almost all cases, the studies described beneficial effects – although the methodological quality of most studies was weak. Main indications were internal/metabolic diseases and psychiatric/neurological disorders.</p> <p>Conclusion</p> <p>Beyond the obvious beneficial effects of warm bathes on the subjective well-being, it remains to be clarified what the unique contribution of the distinct essential oils dispersed in the water can be. There is a lack of clinical studies exploring the efficacy of oil-dispersion baths. Such studies are recommended for the future.</p

The adaptive significance of chromosomal inversion polymorphisms in Drosophila melanogaster

Chromosomal inversions, structural mutations that reverse a segment of a chromosome, cause suppression of recombination in the heterozygous state. Several studies have shown that inversion polymorphisms can form clines or fluctuate predictably in frequency over seasonal time spans. These observations prompted the hypothesis that chromosomal rearrangements might be subject to spatially and/or temporally varying selection. Here, we review what has been learned about the adaptive significance of inversion polymorphisms in the vinegar fly Drosophila melanogaster, the species in which they were first discovered by Sturtevant in 1917. A large body of work provides compelling evidence that several inversions in this system are adaptive; however, the precise selective mechanisms that maintain them polymorphic in natural populations remain poorly understood. Recent advances in population genomics, modelling and functional genetics promise to greatly improve our understanding of this long‐standing and fundamental problem in the near future

Biophysical and functional studies of neurotensin receptor 1

G protein coupled receptors (GPCRs) are a large family of membrane proteins that facilitate diverse cellular signalling processes and represent significant drug targets. There has been considerable progress in understanding the molecular process of GPCR activation, but structural, biophysical & functional studies of GPCRs typically make use of a small number of well-studied receptors, sometimes with heavily modified sequences and often in the absence of the lipid environments in which GPCRs have evolved to be functional. In this thesis, the neurotensin receptor 1 (NTS1) is used as a model GPCR to explore aspects of receptor dynamics and function, with emphasis on the use of minimally modified receptor sequences. Firstly, using site-specific cysteine mutants and an E. coli expression system, the conformational dynamics of the proximal C-terminus of NTS1 were defined for the receptor in a native-like lipid environment, resolving a literature dispute concerning the structure of ‘helix 8’ for NTS1. Secondly, production of NTS1 and the heterotrimeric G proteins Gq and Gi1 was established using insect cell expression systems, and high-quality native mass spectra were obtained for NTS1 that demonstrate receptor palmitoylation, and pave the way for the study of post-translational modifications of GPCRs by native mass spectrometry. Thirdly, using a GTP turnover assay, lipids were identified which selectively enhanced NTS1-Gq over NTS1-Gi1 coupling, suggesting a role for membrane composition in selectivity of NTS1 signalling. Finally, the novel polymethacrylate (PMA) amphipathic polymer was used to establish detergent-free purification of NTS1, representing the first detergent-free purification of any membrane protein using PMA. The work presented here thus progresses the field, both in terms of our molecular understanding of GPCR signalling and in terms of technical advances that will facilitate further studies.</p