International Journal of Laboratory HematologyVolume 38, Issue 4 p. e86-e88 Letter to the Editor Results of a prepilot study of potential test material for the external quality assessment of reticulocyte haemoglobin content R. F. Hinchliffe, R. F. Hinchliffe UK NEQAS Haematology General Scientific Advisory Group, Watford, UKSearch for more papers by this authorA. Mahon, A. Mahon UK NEQAS Haematology, Watford, UKSearch for more papers by this authorW. Thomas, W. Thomas UK NEQAS Haematology General Scientific Advisory Group, Watford, UKSearch for more papers by this authorC. J. Doré, C. J. Doré orcid.org/0000-0001-9796-4970 UK NEQAS Haematology, Watford, UKSearch for more papers by this authorC. Briggs, C. Briggs UK NEQAS Haematology General Scientific Advisory Group, Watford, UKCarol Briggs died on 25th February 2015.Search for more papers by this authorB. De la Salle, B. De la Salle barbara.delasalle@whht.nhs.uk UK NEQAS Haematology, Watford, UKSearch for more papers by this authorK. Hyde, K. Hyde UK NEQAS Haematology, Watford, UKSearch for more papers by this author R. F. Hinchliffe, R. F. Hinchliffe UK NEQAS Haematology General Scientific Advisory Group, Watford, UKSearch for more papers by this authorA. Mahon, A. Mahon UK NEQAS Haematology, Watford, UKSearch for more papers by this authorW. Thomas, W. Thomas UK NEQAS Haematology General Scientific Advisory Group, Watford, UKSearch for more papers by this authorC. J. Doré, C. J. Doré orcid.org/0000-0001-9796-4970 UK NEQAS Haematology, Watford, UKSearch for more papers by this authorC. Briggs, C. Briggs UK NEQAS Haematology General Scientific Advisory Group, Watford, UKCarol Briggs died on 25th February 2015.Search for more papers by this authorB. De la Salle, B. De la Salle barbara.delasalle@whht.nhs.uk UK NEQAS Haematology, Watford, UKSearch for more papers by this authorK. Hyde, K. Hyde UK NEQAS Haematology, Watford, UKSearch for more papers by this author First published: 16 June 2016 https://doi.org/10.1111/ijlh.12514Citations: 1 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume38, Issue4August 2016Pages e86-e88 RelatedInformation
Less developed countries (LDC) often suffer from development malaise caused by discrepancies between export dreams and development structures. A major economic activity of LDC’s is in many cases concerned with raw material development for export. Infrastructure development, an internal economic activity, is often ignored even though such an economic goal could enhance export of raw goods. Without internal development, LDC’s remain dependent on activities requiring little capital support, i.e., subsistence agriculture. If such countries are to gain economic independence, both external and internal development objectives must be met to reduce dependence on subsistence agriculture and raise the capacity of the nation for self-generating economic growth. A major problem is the coordination of the internal and external development policies so as not to seriously limit each other. In this respect, governments often attempt to facilitate both of these activities by acting as an employer and an administrator for a substantial range of marketing and infrastructural development programs.
A series of N-formyl hydroxylamine peptide deformylase inhibitors containing a cyclic azaamino acid moiety between the P1' and P3' substituents are presented. Selected compounds display antibacterial activity against pathogens associated with respiratory tract infections with representative compounds showing excellent MICs against Haemophilus influenzae.
Today's sales managers face a tough challenge. They must be more productive than ever while relying more on partners and technology with reduced resources in the field. And with fewer, larger customers, every decision becomes more important -- and riskier. The Sales Manager's Success Manual provides the critical information sales managers need to succeed in this increasingly difficult job. Covering fundamental sales management topics including compensation, forecasting, and motivation, along with more advanced topics such as dealing with internal politics, understanding generational issues, managing up, and developing intuition, the book shows readers how to:* hire the best sales force * foresee potential surprises * help reps make better decisions * save time and resources * target accurately for better results * work with the CEO and the rest of the companyPacked with savvy advice, enlightening case studies, and no-nonsense know-how, The Sales Manager's Success Manual is a one-of-a-kind book no sales manager should be without.
A series of analogues of the peptide deformylase (PDF) inhibitor BB-3497 where the P3' amide bond was replaced with a ketone functionality is described. The in vitro antibacterial profiling of these compounds revealed that they demonstrate activity against pathogens associated with respiratory tract infections.
Structural modifications to the peptide deformylase inhibitor BB-3497 are described. In this paper, we describe the initial SAR around this lead for modifications to both the P2′ and P3′ side chains. Enzyme inhibition and antibacterial activity data revealed that a variety of substituents are tolerated at the P2′ and P3′ positions of the inhibitor backbone. The data from this study highlights the potential for modification at the P2′ and P3′ positions to optimise the physicochemical properties.
This article investigates the reasons underlying the high propensity of UK firms to directly invest in the United States via acquisition and merger. Using a binomial logit model, this study analyses data from 142 firms in five industrial sectors over the period 1984–1994. Together, these sectors account for more than 80% of UK foreign direct investment (FDI) in the sample period. The results highlight the role of diversification in explaining this behaviour. In contrast, the relative lack of evidence to support the role of exchange rates and leverage in influencing the decision to merge/acquire continues to fuel division as to the role of capital market imperfections in determining mode of entry.
Structural modifications to the peptide deformylase inhibitor BB-3497 are described. In this paper, we describe the initial SAR around this lead for modifications to the methylene spacer and the P1' side chain. Enzyme inhibition and antibacterial activity data revealed that the optimum distance between the N-formyl hydroxylamine metal binding group and the P1' side chain is one unsubstituted methylene unit. Additionally, lipophilic P1' side chains that closely mimic the methionine residue in the substrate provided compounds with the best microbiological profile.
A series of analogues of the potent peptide deformylase (PDF) inhibitor BB-3497 containing alternative metal binding groups was synthesised. Enzyme inhibition and antibacterial activity data for these compounds revealed that the bidentate hydroxamic acid and N-formyl hydroxylamine structural motifs represent the optimum chelating groups on the pseudopeptidic BB-3497 backbone.
The intention to continue on to post-compulsory education of students at the age of 16 is examined with particular focus on the contributory effects of peer groups and educational experience. Using random effects nominal logistic regression analysis and data from the Bradford Youth Cohort (1998 sweep), our results suggest that expected grades have a powerful influence on the decision to stay on. For boys, the impression of teachers, peer groups and undertaking work experience are all important in this decision making process; this is not the case for girls. These results could inform policy makers on which strategies to use to increase participation. * Corresponding author. Tel.: (+44/0) 117 344 2366. Fax: (+44/0) 117 344 2295. Email: Wayne.Thomas@uwe.ac.uk We would like to acknowledge Fiona Walton who organised and led the original study, Bradford Training Enterprise Council for funding and supporting the original study, all of the schools that participated and the young people who completed the questionnaires. Additional thanks to Rachel Chapman, Alex Upton and the Survey Research Centre at the Policy Research Institute, Leeds Metropolitan University. Any remaining errors are the authors’ responsibility.
Peptide deformylase (PDF) is an essential bacterial metalloenzyme which deformylates the N-formylmethionine of newly synthesized polypeptides and as such represents a novel target for antibacterial chemotherapy. To identify novel PDF inhibitors, we screened a metalloenzyme inhibitor library and identified an N-formyl-hydroxylamine derivative, BB-3497, and a related natural hydroxamic acid antibiotic, actinonin, as potent and selective inhibitors of PDF. To elucidate the interactions that contribute to the binding affinity of these inhibitors, we determined the crystal structures of BB-3497 and actinonin bound to Escherichia coli PDF at resolutions of 2.1 and 1.75 A, respectively. In both complexes, the active-site metal atom was pentacoordinated by the side chains of Cys 90, His 132, and His 136 and the two oxygen atoms of N-formyl-hydroxylamine or hydroxamate. BB-3497 had activity against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis, and activity against some gram-negative bacteria. Time-kill analysis showed that the mode of action of BB-3497 was primarily bacteriostatic. The mechanism of resistance was via mutations within the formyltransferase gene, as previously described for actinonin. While actinonin and its derivatives have not been used clinically because of their poor pharmacokinetic properties, BB-3497 was shown to be orally bioavailable. A single oral dose of BB-3497 given 1 h after intraperitoneal injection of S. aureus Smith or methicillin-resistant S. aureus protected mice from infection with median effective doses of 8 and 14 mg/kg of body weight, respectively. These data validate PDF as a novel target for the design of a new generation of antibacterial agents.
The main purine analogues with activity against lymphoid malignancies are fludarabine, cladribine and pentostatin, all of which are active against slowly proliferating cells through their inhibition of DNA repair and therefore have significant synergistic activity with cytotoxic agents which cause DNA damage. Combinations of purine analogues and alkylating agents or platinum compounds result in markedly increased activity but at the expense of more severe haematological toxicity, while evidence of synergy with anthracyclines/anthracenediones is apparent in the treatment of malignant lymphoma. Interaction between fludarabine or cladribine with deoxycytidine kinase results in a significant enhancement of the activity of cytarabine. Unexpected evidence of clinical synergy is also apparent in combinations of purine analogues and anti-CD20 monoclonal antibodies.
Matrix metalloproteinase inhibitors of general formula (1) were synthesised by a route involving an Ireland-Claisen rearrangement which enables systematic modification of the substituent alpha to the hydroxamic acid. An analogue (12c) possessing an alpha-cyclopentyl group is a potent broad spectrum inhibitor that displays high and sustained blood levels following oral dosing in both the rat and marmoset ex-vivo bioassays. This compound and analogues are also potent inhibitors of TNF alpha release.
Tumor necrosis factor-alpha (TNF-alpha) is released from a cell membrane-anchored precursor by proteolytic cleavage. We have shown that broad spectrum synthetic inhibitors of matrix metalloproteinases (MMPs) prevent the processing of the TNF precursor but do not inhibit the release of other cytokines. Purified MMPs, stromelysin, matrilysin, collagenase, and the gelatinases can all cleave a recombinant pro-TNF substrate to yield mature TNF. MMP inhibitors prevent the rise in blood levels of TNF after endotoxin administration in rats and are effective in animal models of inflammatory disease such as adjuvant arthritis. Drugs that inhibit MMP action and TNF release show great promise for the treatment of autoimmune inflammatory diseases.
Examines the development of friction plunge welding, a new technique for joining dissimilar material combinations. Describes the principles of this welding method and gives its advantages over traditional rotary friction welding. Concludes that it provides an alternative method of manufacture for products such as engine valve seats, end connections and cappings and tube to plate transition joints. The new technique also has potential for joining thermoset to thermoplastic materials.
Currently most managers in the Alaska reindeer industry utilize an extensive management plan in operating their enterprises. This plan does not incorporate the use of a planned rotational grazing system. To investigate the possibility of enhancing economic returns, a simulated reindeer operation is modeled using a linear programming framework. Included within the model are three management plans, including the present plan and two more intensive management approaches.The two alternatives incorporate the use of rotational grazing. Model results suggest that both the economic performance of a reindeer enterprise and the economic productivity of reindeer range would be substantially improved by employing a more intensive management plan that utilizes a five‐year rotational grazing system. Shadow prices from the model's forage constraint are used to calculate annual rental values for different range types. The policy implications of these values are examined through a discussion of the possible implementation of grazing fees and the opportunity cost of allocating the rangeland for caribou use.De nos jours la plupart des régisseurs dans l'industrie des rennes en Alaska utilise un projet de régie extensif. Ce projet ne contient pas l'usage d'un projet de pâturage en rotation. Pour analyser la possibilité d'augmentation des profits, on utilise un modèle d'une operation des rennes, simulé avec un réseau de programmes linéaires. Compris dans le modèle sont trois projets de régie, le projet actuel et deux autres méthodes de régie intensives.Les deux alternatives contiennent l'usage d'un projet de pâturage en rotation. Les résultats des modèles proposent que le rendement économique d'un entreprise de rennes et la productivité du territoire des rennes seraient améliorés fondamentalement avec l'emploi d'un projet de régie plus intensif. Ce projet utilise un système de pâturage en rotation pendant cinq ans. On utilise des prix “shadow” (additionelles) du fourrage dans ce modèle pour calculer les loyers annuels pour les types différents de territoire. On examine aussi les consequences théoriques des méthodes en face des ces valeurs dans une discussion de la mise en vigueur possible des droits de pâturage et le côut de consacrer les territoires à l'usage des caribou.