Water and the Biology of Prions and Plaques

This is an attempt to account for the insolubility and/or aggregation of prions and plaques in terms of a model of water consisting of an equilibrium between high 
density and low density microdomains. Hydrophobic molecules, including proteins, 
accumulate selectively into stable populations, enriched in high density water, at 
charged sites on biopolymers. In enriched high density water, proteins are probably 
partially unfolded and may precipitate out when released. All extracellular matrices 
contain such charged polymers. Prions, which have been shown to accumulate in soils 
and clays containing silicates and aluminates also probably accumulate in 
extracellular matrices. 
 
Release of proteins follows hydrolysis of the charged groups by highly reactive high 
density water. This is normally a slow process but is greatly accelerated by urea. 
Plaques may form with age and disease because of accumulation of urea and, perhaps, 
glucose in the blood. This favours precipitation of proteins emerging from matrices, 
rather than refolding and solution. Dialysis should, therefore, interfere with plaque 
formation and impede the development of some age-related diseases

Science is fundamentally a peer-to-peer process and online communities will shape the evolution of scholarly publishing

The transformation of publishing models and platforms remains a recurrent issue for the scholarly community to grapple with given new technologies. Graham Steel provides an overview of a recent conference on the role and evolution of scholarly publishing offering an expansive look at how digital technology will continue to support the advancement of science for the widest possible audience

Visualising First-Order Proof Search

This paper describes a method for visualising proof search in automatic resolution-style first-order theorem provers. The method has been implemented in a simple tool called viz, which takes advantage of the widely-supported scalar vector graphics format to produce graphs which can be viewed interactively. This allows the user to zoom in and out, pan, and get more information by clicking on particular parts of the graph. We demonstrate how the graphs can be used to suggest improvements to the strategy and heuristics used in the proof attempt

Ruthenium picolinates for photosensitisation of heterogeneous water oxidation

Catalytic photochemical water oxidation is one of the key problems in the development of both the generation of solar fuels and renewable chemical feed stocks. One of the leading proposals is to use heterogeneous semiconductors, which, when under irradiation, generate a large enough voltage to electrolyse water molecules in situ. To the effectiveness of this process, dye sensitisers are employed to harvest more of the high intensity visible spectrum. The purpose of this thesis is to gain a better understanding of how these dyes behave in combination with selected substrates, and to examine how, with minor alterations to existing dyes, their effectiveness could be improved. Chapter I consists of a survey of various different water oxidation methods found in both nature and in the lab, to build an understanding of both homogenous and heterogeneous water oxidation pathways and how they are connected. Chapter II details the synthesis, characterisation and catalytic testing of a series of ruthenium (IV)based dyes, deriving from ethylcarboxylate-substituted picolinic acid. The investigation determined that significant shifts in the redox couples could be achieved via the simple variation of the substitution pattern of the ethylcarboxylates. What was also discovered was the reduced form of the dyes and the subsequent exchange of charge-carrying ligands for neutral aqua groups. In chapter III, DFT and TDDFT calculations were performed in order to gain a more fundamental understanding of the behaviour of these dyes at a molecular level. The results show that the complexes are reducing upon contact with water, as the experimental UV-Vis spectra match those of the reduced species rather than the original ruthenium (IV) dyes. This reduction is attributed to the complexes acting as water-oxidation agents due to the high oxidation potential of their Ru III/IV couples in comparison with that of the water oxidation reaction. Attempts to develop similar ruthenium-amide based dyes are discussed in chapter IV. What was discovered was that, while the ligands could be synthesised easily, the complexes proved to be unstable and unsuitable for the water oxidation reaction. Overall these studies show that small changes in ligand design, such as variation in anchoring position, can have pronounced effects on the characteristics of those dyes and highlight the need for systematic exploration of ruthenium based dye sensitisers if improvements to the heterogeneous water oxidation reaction are going to occur.Catalytic photochemical water oxidation is one of the key problems in the development of both the generation of solar fuels and renewable chemical feed stocks. One of the leading proposals is to use heterogeneous semiconductors, which, when under irradiation, generate a large enough voltage to electrolyse water molecules in situ. To the effectiveness of this process, dye sensitisers are employed to harvest more of the high intensity visible spectrum. The purpose of this thesis is to gain a better understanding of how these dyes behave in combination with selected substrates, and to examine how, with minor alterations to existing dyes, their effectiveness could be improved. Chapter I consists of a survey of various different water oxidation methods found in both nature and in the lab, to build an understanding of both homogenous and heterogeneous water oxidation pathways and how they are connected. Chapter II details the synthesis, characterisation and catalytic testing of a series of ruthenium (IV)based dyes, deriving from ethylcarboxylate-substituted picolinic acid. The investigation determined that significant shifts in the redox couples could be achieved via the simple variation of the substitution pattern of the ethylcarboxylates. What was also discovered was the reduced form of the dyes and the subsequent exchange of charge-carrying ligands for neutral aqua groups. In chapter III, DFT and TDDFT calculations were performed in order to gain a more fundamental understanding of the behaviour of these dyes at a molecular level. The results show that the complexes are reducing upon contact with water, as the experimental UV-Vis spectra match those of the reduced species rather than the original ruthenium (IV) dyes. This reduction is attributed to the complexes acting as water-oxidation agents due to the high oxidation potential of their Ru III/IV couples in comparison with that of the water oxidation reaction. Attempts to develop similar ruthenium-amide based dyes are discussed in chapter IV. What was discovered was that, while the ligands could be synthesised easily, the complexes proved to be unstable and unsuitable for the water oxidation reaction. Overall these studies show that small changes in ligand design, such as variation in anchoring position, can have pronounced effects on the characteristics of those dyes and highlight the need for systematic exploration of ruthenium based dye sensitisers if improvements to the heterogeneous water oxidation reaction are going to occur

On the mark? Responses to a sting

A series of responses to John Bohannon's "sting" operation on OA journals

On a problem of Andersson and Perlman

We present a simple solution to a problem posed recently by Andersson and Perlman. This solution allows us to find the conditional independence assumptions necessary to permit maximum likelihood estimation of the parameters of a multivariate normal distribution, when certain observations are missing

Primary health care case management through the lens of complexity: an exploratory study of naturopathic practice using complexity science principles.

BACKGROUND: Advances in systems science creates an opportunity to bring a complexity perspective to health care practices and research. While medical knowledge has greatly progressed using a reductionist and mechanistic philosophy, this approach may be limited in its capacity to manage chronic and complex illness. With its holistic foundation, naturopathy is a primary health profession with a purported alignment with a complexity perspective. As such this pilot study aimed to investigate the application of complexity science principles, strategies, and tools to primary health care using naturopathy as a case study. METHODS: A network mapping and analysis of the naturopathic case management process was conducted. Mind maps were created by naturopathic practitioners to reflect their clinical conceptualisation of a common paper clinical case. These mind maps were inputed into Gephi, a network mapping, exploration, and analysis software. Various layouts of the data were produced, and these were analysed using exploratory data analysis and computational network analysis. RESULTS: Seven naturopathic practitioners participated in the study. In the combined network mapping, 133 unique elements and 399 links were identified. Obesity, the presenting issue in the case, was centrally located. Along with obesity, other keystone elements included: systemic inflammation, dysbiosis, diet, the liver, and mood. Each element was connected on average to 3.05 other elements, with a degree variation between one and 36. Six communities within the dataset were identified, comprising: the nervous system and mood, gastroinstetinal and dietary factors, systemic inflammation and obesity, the endocrine system and metabolism. CONCLUSIONS: This pilot study demonstrates that it is feasible to apply a complexity science perspective to investigating primary health care case management. This supports a shift to viewing the human organism as a complex adaptive system within primary health care settings, with implications for health care practices that are more cognisant with the treatment of chronic and complex conditions and research opportunities to capture the complex clinical reasoning processes of practitioners

The converging paradigms of holism and complexity: An exploration of naturopathic clinical case management using complexity science principles.

RATIONALE: Traditional whole systems of medicine, such as naturopathy, are founded upon holism; a philosophical paradigm consistent with contemporary complexity science. Naturopathic case management is predicated upon the understanding of an intimately interconnected internal physiological and external context of the human organism-potentially indicating a worldview aligned with a complexity perspective. In this study we investigate naturopathic clinical reasoning using a complexity lens with the aim of ascertaining the extent of correspondence between the two. METHOD: Mind maps depicting case presentations were sought from Australian degree qualified naturopaths. A network mapping was undertaken, which was then analysed in accordance with a complexity science framework using exploratory data analysis and network analysis processes and tools. RESULTS: Naturopathic case schematics, in the form of mind maps (n = 70), were collected, network mapped, and analysed. A total of 739 unique elements and 2724 links were identified across the network. Integral elements across the network were: stress, fatigue, general anxiety, systemic inflammation, gut dysbiosis, and diet. A modularity algorithm detected 11 communities, the primary ones of these representing the nervous system and mood; the gastrointestinal tract, liver, and nutrition; immune function and the immune system; and diet and nutrients. CONCLUSIONS: Naturopathic case management is holistic and based on a perspective of an integrated physiology and external context of the human organism. The traditional concept of holism, when subjected to a complexity lens, leads to the emergence of a contemporary holistic paradigm cognisant of the human organism being a complex system. The application of complexity science to investigate naturopathic case management as employed in this study, demonstrates that it is possible to investigate traditional philosophies and principles in a scientific and critical manner. A complexity science research approach may offer a suitable scientific paradigm to develop our understanding of traditional whole systems of medicine

Tetradentate Schiff base beryllium complexes

The structure of (BeSalen)2 is reported. The incompatibility of the geometry of the beryllium with the inflexibility of the Salen ligand gives rise to a rare dimeric bis-didentate motif