Vaginal microbicides for the prevention of HIV transmission

The human immunodeficiency virus (HIV) kills more people worldwide than any other infectious disease. Approximately 42 million people, mostly in Africa and Asia, are currently infected with HIV (Figure 3.1), and 5 million new infections occur every year (AIDS Epidemic Update, 2002). It is estimated that 22 milIion people have died since the first clinical evidence of AIDS (acquired immunodeficiency syndrome) emerged in 1981 ('Mobilization for Microbicides' ~ The Rockfeller Foundation). HIV is generally transmitted in one of three ways: through unprotected sexual intercourse, blood-to-blood contact, and mother-to-child transmission. Once the virus has entered the body, it invades the cells of the immune system and initiates the production of new virus particles with concomitant destruction of the immune cells. As the number of immune cells in the body slowly declines, weight loss, debilitation, and eventually death occur due to opportunistic infections or cancers. Although AIDS is presently incurable, highly active antiretroviral therapy (HAART), where a cocktail of potent antiretroviral drugs are administered daily to HIV-positive patients to control the viral load, has resulted in dramatic reductions in HIV-related morbidity and mortality in the developed world

Validation of protein carbonyl measurement:a multi-centre study

Protein carbonyls are widely analysed as a measure of protein oxidation. Several different methods exist for their determination. A previous study had described orders of magnitude variance that existed when protein carbonyls were analysed in a single laboratory by ELISA using different commercial kits. We have further explored the potential causes of variance in carbonyl analysis in a ring study. A soluble protein fraction was prepared from rat liver and exposed to 0, 5 and 15 min of UV irradiation. Lyophilised preparations were distributed to six different laboratories that routinely undertook protein carbonyl analysis across Europe. ELISA and Western blotting techniques detected an increase in protein carbonyl formation between 0 and 5 min of UV irradiation irrespective of method used. After irradiation for 15 min, less oxidation was detected by half of the laboratories than after 5 min irradiation. Three of the four ELISA carbonyl results fell within 95% confidence intervals. Likely errors in calculating absolute carbonyl values may be attributed to differences in standardisation. Out of up to 88 proteins identified as containing carbonyl groups after tryptic cleavage of irradiated and control liver proteins, only seven were common in all three liver preparations. Lysine and arginine residues modified by carbonyls are likely to be resistant to tryptic proteolysis. Use of a cocktail of proteases may increase the recovery of oxidised peptides. In conclusion, standardisation is critical for carbonyl analysis and heavily oxidised proteins may not be effectively analysed by any existing technique.

Lean viewed as a philosophy

Purpose - The purpose of this paper is to act as a meticulous conceptual paper probing the contemporary view towards lean and illustrate that, despite its discernible benefits, the implementation record suffers as the prevailing opinion fails to encapsulate that an aspiring lean enterprise shall only succeed if it views lean as a philosophy rather than another strategy. Design/methodology/approach - The paper is based on a thorough literature search concerning the success and failure of lean implementations and acts as a precursor for one of the authors utilising a combination of methodologies; namely, interviewing, survey questionnaire and participant observation in attempting to prove his PhD hypothesis. Findings - Evidently, a cocktail of factors are needed for lean success; not only is it necessary to implement most of the technical tools but an organisation's culture needs transforming too. Furthermore, the alterations need to be implemented throughout an organisation's value chain. Lean has a major strategic significance, though its implementation procedure, HRM implications, general approach to the supplier base coupled with the overall universal conviction of viewing lean as a set of tactics rather than embracing it as a philosophy advocates that this contributes to the relatively low number of successful lean initiatives. Originality/value - The paper would prove invaluable to lean practitioners through its summation of the intricacies towards lean enterprise success and academic researchers by focusing their attention towards the necessary cultural implications. © Emerald Group Publishing Limited.

Mixing the grant cocktail:towards an understanding of the outcomes of financial support to small firms

One of the key policy objectives of government at national and regional level, is to overcome the constraints preventing local industry achieving greater competitiveness in the international market-place. This paper examines the impact of grant assistance to Northern Ireland small firms delivered over the period 1994 ^ 97 by the former Local Enterprise Development Unit through its Growth Business Support Programme (GBSP). Previous work by the authors showed that there was some tentative evidence to suggest a link between employment growth and grant aid provided to very small firms (fewer than 10 employees) assisted under the GBSP. The central objective of the empirical work reported in this paper is to extend the previous analysis by understanding the extent to which the value of financial assistance influences growth (employment, turnover, and productivity measures) and if differential impacts arise depending on the nature and timing (lag structures) of the grant assistance.

Forced retroevolution of an RNA bacteriophage

The operator hairpin ahead of the replicase gene in RNA bacteriophage MS2 contains overlapping signals for binding the coat protein and ribosomes. Coat protein binding inhibits further translation of the gene and forms the first step in capsid formation. The hairpin sequence was partially randomized to assess the importance of this structure element for the bacteriophage and to monitor alternative solutions that would evolve on the passaging of mutant phages. The evolutionary reconstruction of the operator failed in the majority of mutants. Instead, a poor imitation developed containing only some of the recognition signals for the coat protein. Three mutants were of particular interest in that they contained double nonsense codons in the lysis reading frame that runs through the operator hairpin. The simultaneous reversion of two stop codons into sense codons has a very low probability of occurring. Therefore the phage solved the problem by deleting the nonsense signals and, in fact, the complete operator, except for the initiation codon of the replicase gene. Several revertants were isolated with activities ranging from 1% to 20% of wild type. The operator, long thought to be a critical regulator, now appears to be a dispensable element. In addition, the results indicate how RNA viruses can be forced to step back to an attenuated form.