The M17 leucine aminopeptidase of the malaria parasite Plasmodium falciparum:importance of active site metal ions in the binding of substrates and inhibitors

The M17 leucine aminopeptidase of the intraerythrocytic stages of the malaria parasite Plasmodium falciparum (PfLAP) plays a role in releasing amino acids from host hemoglobin that are used for parasite protein synthesis, growth, and development. This enzyme represents a target at which new antimalarials could be designed since metalloaminopeptidase inhibitors prevent the growth of the parasites in vitro and in vivo. A study on the metal ion binding characteristics of recombinant P. falciparum M17 leucine aminopeptidase (rPfLAP) shows that the active site of this exopeptidase contains two metal-binding sites, a readily exchangeable site (site 1) and a tight binding site (site 2). The enzyme retains activity when the metal ion is removed from site 1, while removal of metal ions from both sites results in an inactive apoenzyme that cannot be reactivated by the addition of divalent metal cations. The metal ion at site 1 is readily exchangeable with several divalent metal ions and displays a preference in the order of preference Zn(2+) > Mn(2+) > Co(2+) > Mg(2+). While it is likely that native PfLAP contains a Zn(2+) in site 2, the metal ion located in site 1 may be dependent on the type and concentration of metal ions in the cytosolic compartment of the parasite. Importantly, the type of metal ion present at site 1 influences not only the catalytic efficiency of the enzyme for peptide substrates but also the mode of binding by bestatin, a metal-chelating inhibitor of M17 aminopeptidases with antimalarial activity.

Ancient manuring practices pollute arable soils at the St Kilda World Heritage Site, Scottish North Atlantic

The impact of ancient fertilization practices on the biogeochemistry of arable soils on the remote Scottish island of Hirta, St Kilda was investigated. The island was relatively unusual in that the inhabitants exploited seabird colonies for food, enabling high population densities to be sustained on a limited, and naturally poor, soil resource. A few other Scottish islands, the Faeroes and some Icelandic Islands, had similar cultural dependence on seabirds. Fertilization with human and animal waste streams (mainly peat ash and bird carcases) on Hirta over millennia has led to over-deepened, nutrient-rich soils (plaggen). This project set out to examine if this high rate of fertilization had adversely impacted the soil, and if so, to determine which waste streams were responsible. Arable soils were considerably elevated in Pb and Zn compared to non-arable soils. Using Pb isotope signatures and analysis of the waste streams, it was determined that this pollution came from peat and turf ash (Pb and Zn) and from bird carcases (Zn). This was also confirmed by (13)C and (15)N analysis of the profiles which showed that soil organic matter was highly enriched in marine-derived C and N compared to non-arable soils. The pollution of such a remote island may be typical of other 'bird culture' islands, and peat ash contamination of marginal arable soils at high latitudes may be widespread in terms of geographical area, but less intense at specific locations due to lower population densities than on Hirta.

Strategies for Effective Management of Health and Safety in Confined Site Construction

The overall aim of this research is to identify and catalogue the numerous managerial strategies for effective management of health and safety on a confined, urban, construction site. A mixed methods methodology was adopted using interviews and focus group discussions on three selected case studies of confined construction sites. In addition to these, a questionnaire survey was used based on the findings from the interviews and the focus group discussions. The top five key strategies include (1) Employ safe system of work plans to mitigate personnel health and safety issues; (2) Inform personnel, before starting on-site, of the potential issues using site inductions; (3) Effective communication among site personnel; (4) Draft and implement an effective design site layout prior to starting on-site; and (5) Use of banksman (traffic co-ordinator) to segregate personnel from vehicular traffic. The construction sector is one of the leading industries in accident causation and with the continued development and regeneration of our urban centres, confined site construction is quickly becoming the norm - an environment which only fuels accident creation within the construction sector. This research aids on-site management that requires direction and assistance in the identification and implementation of key strategies for the management of health and safety, particularly in confined construction site environments.

Organization specific predictors of job satisfaction: findings from a Canadian multi-site quality of work life cross-sectional survey

Background: Organizational features can affect how staff view their quality of work life. Determining staff perceptions about quality of work life is an important consideration for employers interested in improving employee job satisfaction. The purpose of this study was to identify organization specific predictors of job satisfaction within a health care system that consisted of six independent health care organizations.

Methods: 5,486 full, part and causal time (non-physician) staff on active payroll within six organizations (2 community hospitals, 1 community hospital/long-term care facility, 1 long-term care facility, 1 tertiary care/community health centre, and 1 visiting nursing agency) located in five communities in Central West Ontario, Canada were asked to complete a 65-item quality of work life survey. The self-administered questionnaires collected staff perceptions of: co-worker and supervisor support; teamwork and communication; job demands and decision authority; organization characteristics; patient/resident care; compensation and benefits; staff training and development; and impressions of the organization. Socio-demographic data were also collected.

Results: Depending on the organization, between 15 and 30 (of the 40 potential predictor) variables were found to be statistically associated with job satisfaction (univariate analyses). Logistic regression analyses identified the best predictors of job satisfaction and these are presented for each of the six organizations and for all organizations combined.

Conclusions: The findings indicate that job satisfaction is a multidimensional construct and although there appear to be some commonalities across organizations, some predictors of job satisfaction appear to be organization and context specific.

The Palisades is a key reference site for the middle Pleistocene of eastern Beringia: New evidence from paleomagnetics and regional tephrostratigraphy

The Palisades, in central Alaska, is one of the most prominent exposures of Quaternary sediments on the Yukon River. Perennially-frozen silt and sand at the Palisades are presently thought to preserve paleoenvironmental records from the Holocene to ~Marine Isotope Stage (MIS) 8 and, beneath a major unconformity, the earliest Pleistocene (~2 Ma). We present new paleomagnetic and tephrochronologic constraints that substantially revise the age of the sediments at the Palisades. We describe 15 new tephra beds, including five beds below the prominent PAL tephra that correlate to known tephra with independent age control from other sites in eastern Beringia. These five known tephra include Chester Bluff tephra, which is present in east-central Alaska and the Yukon, and the newly named Alyeska Pipeline and Taylor Highway tephra from central Alaska; all are constrained to the middle Pleistocene. Paleomagnetic transects from the base of the bluff to the MIS 5e forest bed yield normal polarity, with the exception of a brief reversal event between Old Crow tephra (124 ± 10 ka) and the MIS 5e forest bed that is likely the first documentation of the Blake paleomagnetic event in Alaskan loess. The detailed tephrostratigraphy and paleomagnetic data collectively suggest that most of the sedimentary record at the Palisades is middle Pleistocene in age. The Palisades thus preserves a rare record of late to middle Pleistocene paleoenvironments with multiple regionally distributed tephra beds. © 2013 Elsevier Ltd.

Life-Cycle Energy Analysis of a Modular/Off-Site Building School

This paper is concerned with assessing the building’s the energy efficiency and qualities of a modular design for the education industry, in order assess the long economic benefits. The research includes a life-cycle energy and cost analysis of the school building design, predicting the impact on the operational cost of the building as a result of the addition of photovoltaic panels. The paper also includes a comparative study between the ECO Modular Solutions building, and a current standard prefabricated school building, quantifying the savings in CO2 emissions and savings in cost.

The role of lipid peroxidation products and oxidative stress in activation of the canonical wingless-type MMTV integration site (WNT) pathway in a rat model of diabetic retinopathy

Our recent studies suggest that activation of the wingless-type MMTV integration site (WNT) pathway plays pathogenic roles in diabetic retinopathy and age-related macular degeneration. Here we investigated the causative role of oxidative stress in retinal WNT pathway activation in an experimental model of diabetes.

The Neolithic site of San Marco, Gubbio (Perugia) Umbria: survey and excavation. 1985-8.

Malone, C. and S. Stoddart, Papers of the British School at Rome, 1992. 60: p. 1-69.

Middle Stone Age (MSA) site distributions in eastern Africa and their relationship to Quaternary environmental change, refugia and the evolution of Homo sapiens

This paper considers the evolution of Homo sapiens in eastern Africa in relation to refugia and bottlenecks around ~200 ka BP, at a macro scale. Middle Stone Age (MSA) lithics, site distributions and locations are analysed in relation to palaeovegetation maps of the last glacial/interglacial cycle, which are used as a proxy for earlier climate cycles. A ‘‘push and pull’’ model is then postulated for the spread of Homo sapiens out of refugia in eastern Africa, involving both volcanism (push) and habitat availability (pull). A date within OIS 5 is suggested for this expansion to other parts of the continent, and potentially further a?eld, contrary to a frequently proposed expansion within OIS 3. ©2008 Elsevier Ltd. All rights reserved.

Supply Chain Management in Confined Site Construction: Strategies to Reduce Delay in the Delivery of Materials to Site

With the increase in construction in dense urban environments, the delays associated with managing the material supply chain to site is called into question. Purpose: The aim of this investigation is to gain the perspective of construction contractors operating in a dense urban environment and the resulting strategies adopted to reduce delays in the delivery of materials to site. Methodology: This is achieved through incorporating a comprehensive literature review on the subject in conjunction with industry interviews with construction professionals in the identification of various management issues and corresponding strategies in the reduction of delays in the delivery of materials to site. Findings: The key issue which emerges is the lack of space for unloading bays while the corresponding key strategy is to schedule deliveries outside peak congestion times. Practical Implication: With confined site construction evident throughout the industry and the noted importance of an effective supply chain, the findings here in further assist on-site management in the daily task of ensuring the effective delivery and off-loading of materials in a complex and hazardous environment. Originality/Value: This research aids on-site management of confined site environments in the coordination of the material supply chain to site.

Confined Site Construction and its Impact on Personnel Productivity

Inner city, confined site construction is quickly becoming the norm within the construction sector. The aim of this paper is to identify and document the effect, if any, that a confined construction site environment has on the productivity of on-site personnel. In order to compile the relevant information and attain appropriate results on the matter in question, a qualitative analytical approach is adopted. This process incorporates multiple cases studies from Ireland, Northern Ireland and USA. From the resulting case studies, a minimum of three individual interviews and focus group seminars are conducted to aid in the collection of the data while also assisting in the confirmation of the factors identified from a critique of the relevant literature. From the resulting case studies and discussions, a list of the key issues pertaining to the on-site productivity of personnel emerged and is documented as follows; 1) Overcrowding of personnel at workstations, 2) Lack of space for the effective movement of personnel on-site, 3) Numerous trades working within the one space on-site. Through identifying the issues highlighted and proactively mitigating or eliminating the factors detailed, on-site management professionals can strive to ensure maximum productivity from the industry’s most important resource – people.

Material Management in Confined Site Construction

The objective of this paper is to identify various managerial issues encountered and resulting strategies adopted, with regards management of materials on confined construction site. This is achieved through classifying the various managerial burdens encountered with the numerous strategies adopted, for the successful management of such confined environments within the realm of materials management.


Through conducting an extensive literature review and detailed interviews, a comprehensive insight into the materials management concerns within a confined construction site environment is envisaged and portrayed. The following are the leading issues highlighted; (1)Lack of adequate storage space, (2)Work place becoming over-crowded, (3)Lack of adequate room for the effective handling of materials and (4)Difficult to transport materials around site. The leading managerial strategies to the management of materials on confined construction sites may be listed in order of importance, as follows; (1)Pre-fabrication and pre-assembly, (2)Providing adequate storage, (3)Space scheduling, (4)Just-In-Time delivery techniques, and (5)Effective design site layout.

Based on the research conducted, it can be concluded, that through effective management of the issues identified along with implementing the various strategies highlighted; successful materials management within a confined construction site environment is attainable.


Innovative Aspect of Paper: An empirical study of three different construction sites in three different countries (Ireland, England and USA) investigating the managerial issues and strategies relating to implementation of materials management in confined construction sites.

SWAT 1:what effects do site visits by the principal investigator have on recruitment in a multicentre randomized trial?

The SWAT (Study Within A Trial) programme has been established to develop a series of studies that would embed research within research, so as to resolve uncertainties about the effects of different ways of designing, conducting, analyzing and interpreting evaluations of health and social care. It was described in an Education piece in the Journal of Evidence-Based Medicine in 2012. We have now prepared the first example of the design summary for a SWAT, using the template that will be used for other SWAT. This is presented in this article.