The Synthesis of Modified Peptide Isosteres As Potential Anti-Parasite Drugs

Protease enzymes are responsible for the catalytic hydrolysis of peptides and therefore play vital roles in the biochemistry of organisms. Serine proteases, which achieve proteolytic cleavage by a mechanism involving an activated serine residue, are numerous in mammalian systems while only a limited number of the analogous cysteine proteases are to be found. Cysteine protease enzymes are however, widespread in parasitic species and often essential to the functioning of the organism. Thus the use of inhibitors for the treatment of parasitic infestation may be possible if the subtle differences between these two enzyme families can be exploited

Bridging the gap between the economic evaluation literature and daily practice in occupational health: a qualitative study among decision-makers in the healthcare sector

Background: Continued improvements in occupational health can only be ensured if decisions regarding the implementation and continuation of occupational health and safety interventions (OHS interventions) are based on the best available evidence. To ensure that this is the case, scientific evidence should meet the needs of decision-makers. As a first step in bridging the gap between the economic evaluation literature and daily practice in occupational health, this study aimed to provide insight into the occupational health decision-making process and information needs of decision-makers.Methods: An exploratory qualitative study was conducted with a purposeful sample of occupational health decision-makers in the Ontario healthcare sector. Eighteen in-depth interviews were conducted to explore the process by which occupational health decisions are made and the importance given to the financial implications of OHS interventions. Twenty-five structured telephone interviews were conducted to explore the sources of information used during the decision-making process, and decision-makers' knowledge on economic evaluation methods. In-depth interview data were analyzed according to the constant comparative method. For the structured telephone interviews, summary statistics were prepared.Results: The occupational health decision-making process generally consists of three stages: initiation stage, establishing the need for an intervention; pre-implementation stage, developing an intervention and its business case in order to receive senior management approval; and implementation and evaluation stage, implementing and evaluating an intervention. During this process, information on the financial implications of OHS interventions was found to be of great importance, especially the employer's costs and benefits. However, scientific evidence was rarely consulted, sound ex-post program evaluations were hardly ever performed, and there seemed to be a need to advance the economic evaluation skill set of decision-makers.Conclusions: Financial information is particularly important at the front end of implementation decisions, and can be a key deciding factor of whether to go forward with a new OHS intervention. In addition, it appears that current practice in occupational health in the healthcare sector is not solidly grounded in evidence-based decision-making and strategies should be developed to improve this. © 2013 van Dongen et al.; licensee BioMed Central Ltd

Under the Skin of a Lion: Unique Evidence of Upper Paleolithic Exploitation and Use of Cave Lion (Panthera spelaea) from the Lower Gallery of La Garma (Spain)

ABSTRACT: Pleistocene skinning and exploitation of carnivore furs have been previously inferred from archaeological evidence. Nevertheless, the evidence of skinning and fur processing tends to be weak and the interpretations are not strongly sustained by the archaeological record. In the present paper, we analyze unique evidence of patterned anthropic modification and skeletal representation of fossil remains of cave lion (Panthera spelaea) from the Lower Gallery of La Garma (Cantabria, Spain). This site is one of the few that provides Pleistocene examples of lion exploitation by humans. Our archaeozoological study suggests that lion-specialized pelt exploitation and use might have been related to ritual activities during the Middle Magdalenian period (ca. 14800 cal BC). Moreover, the specimens also represent the southernmost European and the latest evidence of cave lion exploitation in Iberia. Therefore, the study seeks to provide alternative explanations for lion extinction in Eurasia and argues for a role of hunting as a factor to take into account

Revisiting the Gaia Hypothesis: Maximum Entropy, Kauffman’s ‘Fourth Law’ and Physiosemeiosis

Recently, Kleidon suggested to analyze Gaia as a non-equilibrium thermodynamic system that continuously moves away from equilibrium, driven by maximum entropy production which materializes in hierarchically coupled mechanisms of energetic flows via dissipation and physical work. I relate this view with Kauffman's 'Fourth Law of Thermodynamics', which I interprete as a proposition about the accumulation of information in evolutionary processes. The concept of physical work is expanded to including work directed at the capacity to work: I offer a twofold specification of Kauffman's concept of an 'autonomous agent', one as a 'self-referential heat engine', and the other in terms of physiosemeiosis, which is a naturalized application of Peirce's theory of signs. The conjunction of these three theoretical sources, Maximum Entropy, Kauffman's Fourth Law, and physiosemeiosis, shows that the Kleidon restatement of the Gaia hypothesis is equivalent to the proposition that the biosphere is generating, processing and storing information, thus directly treating information as a physical phenomenon. There is a fundamental ontological continuity between the biological processes and the human economy, as both are seen as information processing and entropy producing systems. Knowledge and energy are not substitutes, with energy and information being two aspects of the same underlying physical process

Colliding Worlds: Asteroid research and the legitimization of war in space

Accepted versio