Phenylalanine-544 plays a key role in substrate and inhibitor binding by providing a hydrophobic packing point at the active site of insulin-regulated aminopeptidase

Inhibitors of insulin-regulated aminopeptidase (IRAP) improve memory and are being developed as a novel treatment for memory loss. In this study, the binding of a class of these inhibitors to human IRAP was investigated using molecular docking and site-directed mutagenesis. Four benzopyran-based IRAP inhibitors with different affinities were docked into a homology model of the catalytic site of IRAP. Two 4-pyridinyl derivatives orient with the benzopyran oxygen interacting with the Zn2+ ion and a direct parallel ring-stack interaction between the benzopyran rings and Phe544. In contrast, the two 4-quinolinyl derivatives orient in a different manner, interacting with the Zn2+ ion via the quinoline nitrogen, and Phe544 contributes an edge-face hydrophobic stacking point with the benzopyran moiety. Mutagenic replacement of Phe544 with alanine, isoleucine, or valine resulted in either complete loss of catalytic activity or altered hydrolysis velocity that was substrate-dependent. Phe544 is also important for inhibitor binding, because these mutations altered the Ki in some cases, and docking of the inhibitors into the corresponding Phe544 mutant models revealed how the interaction might be disturbed. These findings demonstrate a key role of Phe544 in the binding of the benzopyran IRAP inhibitors and for optimal positioning of enzyme substrates during catalysis.

Heraclitus : a LFSR-based stream cipher with key dependent structure

We describe Heraclitus as an example of a stream cipher that uses a 128 bit index string to specify the structure of each instance in real time: each instance of Heraclitus will be a stream cipher based on mutually clocked shift registers. Ciphers with key-dependent structures have been investigated and are generally based on Feistel networks. Heraclitus, however, is based on mutually clocked shift registers. Ciphers of this type have been extensively analysed, and published attacks on them will be infeasible against any instance of Heraclitus. The speed and security of Heraclitus makes it suitable as a session cipher, that is, an instance is generated at key exchange and used for one session.

Key predistribution scheme using finite fields and reed muller codes

Resource constraint sensors of a Wireless Sensor Network (WSN) cannot afford the use of costly encryption techniques like public key while dealing with sensitive data. So symmetric key encryption techniques are preferred where it is essential to have the same cryptographic key between communicating parties. To this end, keys are preloaded into the nodes before deployment and are to be established once they get deployed in the target area. This entire process is called key predistribution. In this paper we propose one such scheme using unique factorization of polynomials over Finite Fields. To the best of our knowledge such an elegant use of Algebra is being done for the first time in WSN literature. The best part of the scheme is large number of node support with very small and uniform key ring per node. However the resiliency is not good. For this reason we use a special technique based on Reed Muller codes proposed recently by Sarkar, Saha and Chowdhury in 2010. The combined scheme has good resiliency with huge node support using very less keys per node.

A health restructure, but the treatment misses some key points

The reforms need more focus on indigenous care, funding transparency and preventative medicine, writes Jim Hyde.

The relationship between coronary heart disease (CHD) and major depressive disorder (MDD) : key mechanisms and the role of quality of life

Various trials have been conducted evaluating depression management programs for patients with Coronary Heart Disease (CHD). However, to date, the most effective way to manage this co-morbidity in the real world setting remains unclear. To better understand the past successes and failures of previous trials and subsequently develop suitable interventions that target key components of health related quality of life (HRQOL) such as mental, physical and vocational functioning, we first need to understand the mechanisms underpinning the relationship between the two conditions. This paper will draw on the key literature in this field as identified by psychiatric, medical and social sciences databases (Cochrane Central Register of Controlled Trials, PubMed, OVID, Medline) available up to January 2012, with the aim to conduct a narrative review which explores: the aetiological relationship between depression and CHD; its association with HRQOL; the relationship between CHD, depression and vocational functioning; and the impact of depression treatment on these outcomes. Key recommendations are made regarding the management of this prevalent co-morbidity in clinical settings.

Using social network analysis to identify key child care center staff for obesity prevention interventions: a pilot study

Introduction. Interest has grown in how systems thinking could be used in obesity prevention. Relationships between key actors, represented by social networks, are an important focus for considering intervention in systems. Method. Two long day care centers were selected in which previous obesity prevention programs had been implemented. Measures showed ways in which physical activity and dietary policy are conversations and actions transacted through social networks (interrelationships) within centers, via an eight item closed-ended social network questionnaire. Questionnaire data were collected from (17/20; response rate 85%) long day care center staff. Social network density and centrality statistics were calculated, using UCINET social network software, to examine the role of networks in obesity prevention. Results. “Degree” (influence) and “betweeness” (gatekeeper) centrality measures of staff inter-relationships about physical activity, dietary, and policy information identified key players in each center. Network density was similar and high on some relationship networks in both centers but markedly different in others, suggesting that the network tool identified unique center social dynamics. These differences could potentially be the focus of future team capacity building. Conclusion. Social network analysis is a feasible and useful method to identify existing obesity prevention networks and key personnel in long day care centers.