Implementation of virtual manufacturing by a technology licensing company

NoThe paper considers the implementation of a virtual manufacturing system as an alternative to outward technology licensing in a high technology industrial sector. Brief theoretical definition and description of the two strategy options is provided to give background and context. This is followed by empirical material from a longitudinal case study of a company that has developed a virtual manufacturing system in addition to its pre-existing outward technology licensing business stream. A summary account of the company history and development is followed by description of the virtual manufacturing proposal. Analysis of this identified a number of competencies that would be required in order to succeed. The final part of the paper describes the company's response to this analysis and discusses early implementation of the virtual system. It is shown that implementation of the proposal has represented a positive response to the business challenges facing the company

Design, Synthesis and Delivery of Peptide-Based Systems

Peptide-based therapeutics have been an active area of research for a number of years. They have been found applications as drug-delivery agents, anticancer therapies and as antibiotics, the latter of which is particularly notable when set against a present-day backdrop of the increasing problem of antibiotic resistance. However, the use of peptides is still limited as they suffer from poor bioavailability as a result of their vulnerability to proteolytic degradation. Peptoids are a class of peptidomimetics which represent a potential proteolytically stable alternative to peptides. Chapter 1 introduces peptoids, common methods of their synthesis and their potential therapeutic applications. The challenges associated with controlling peptoid secondary structure are also discussed, along with commonly seen methods of imposing conformational rigidity. Chapter 2 details our attempts to address this problem by synthesising a library of biaryl-containing cyclic peptoids which represent novel peptoid scaffolds. In Chapter 3, we synthesise the active domain (p15) of the known anticancer peptide CIGB-300 along with three stapled analogues on which binding assays can be carried out. In Chapter 4, we synthesise six cell-penetrating peptoids (CPPos) which have previously been reported to localise in mitochondria. Onto these peptoids we conjugated the known anticancer peptide D-KLA and show the ability of these peptoids to increase proapoptotic activity. Flow cytometry and confocal microscopy is then used to demonstrate mitochondrial localisation of the most active peptide-peptoid hybrid, KLA-CPPo6. Having shown the ability of CPPos to transport biologically active cargo, we then conjugate the p15 peptide, previously introduced in Chapter 3, to the six CPPos in preparation for the evaluation of their anticancer activity

Floral morphogenesis in Primula : inheritance of mutant phenotypes, heteromorphy, and linkage analysis

Interest in Primula flowers from both a horticultural and scientific perspective dates back over 400 years. Floral mutations were first used for ornamental value in the latter part of the 16th Century but had attracted little scientific attention. The phenomenon of floral heteromorphy as a mechanism to promote out-breeding was immortalised by the work of Darwin in the mid 19th Century. Subsequent analysis of this breeding system has attracted much attention, including the genetic definition of the S locus as a cluster of tightly linked genes that control pin and thrum flower development and mediate self-incompatibility. Mutant phenotypes of British Primula have been collected by the author for over twenty years. Classical genetic analysis of some of these mutants is included and provides the first detailed analysis of existing and new mutant phenotypes. Genetic analysis of these mutants is presented in the context of the ABC model of flower development. Detailed analysis of the early ontogeny of wild type and mutant flowers by scanning electron microscopy provides new insights into the control of Primula flower development. As Primula flowers were found to be homomorphic during early ontogeny development of pin and thrum heteromorphic features of Primula were investigated to maturity. A new heteromorphic feature was discovered; thrum flowers have a wider corolla tube mouth than pin flowers due to the corolla tube cells above the anthers being wider in thrum flowers than in pin flowers. Three of the mutant phenotypes Hose in Hose, Staminoid Carpels and sepaloid are predicted to arise through misexpression of a B function gene. The first two are dominant mutant phenotypes and all are linked to the S locus. A fourth recently discovered dominant mutant phenotype, Oakleaf, affects both leaf and flower development, and is also linked to 1he S locus. As 1he dominant nature of the Hose in Hose mutation precludes complementation tests three point crosses were used both as segregation tests and for mapping genes linked to the Primula S locus. Gene order was found to be Oak Leaf, S locus, Hose in Hose, with sepaloid either allelic to Hose in Hose or very tightly linked. In combination, these analyses have enabled 1he assembly of the first genetic map of genes around the S locus including flanking markers on either side

Public-private delivery of insecticide-treated nets: a voucher scheme in Volta Region, Ghana.

BACKGROUND: Coverage of vulnerable groups with insecticide-treated nets (ITNs) in Ghana, as in the majority of countries of sub-Saharan Africa is currently low. A voucher scheme was introduced in Volta Region as a possible sustainable delivery system for increasing this coverage through scale-up to other regions. Successful scale-up of public health interventions depends upon optimal delivery processes but operational research for delivery processes in large-scale implementation has been inadequate. METHODS: A simple tool was developed to monitor numbers of vouchers given to each health facility, numbers issued to pregnant women by the health staff, and numbers redeemed by the distributors back to the management agent. Three rounds of interviews were undertaken with health facility staff, retailers and pregnant women who had attended antenatal clinic (ANC). RESULTS: During the one year pilot 25,926 vouchers were issued to eligible women from clinics, which equates to 50.7% of the 51,658 ANC registrants during this time period. Of the vouchers issued 66.7% were redeemed by distributors back to the management agent. Initially, non-issuing of vouchers to pregnant women was mainly due to eligibility criteria imposed by the midwives; later in the year it was due to decisions of the pregnant women, and supply constraints. These in turn were heavily influenced by factors external to the programme: current household ownership of nets, competing ITN delivery strategies, and competition for the limited number of ITNs available in the country from major urban areas of other regions. CONCLUSION: Both issuing and redemption of vouchers should be monitored as factors assumed to influence voucher redemption had an influence on issuing, and vice versa. More evidence is needed on how specific contextual factors influence the success of voucher schemes and other models of delivery of ITNs. Such an evidence base will facilitate optimal strategic decision making so that the delivery model with the best probability of success within a given context is implemented. Rigorous monitoring has an important role to play in the successful scaling-up of delivery of effective public health interventions

Exploring N-acyl-4-azatetracyclo[5.3.2.0.0]dodec-11-enes as 11β-HSD1 Inhibitors

We recently found that a cyclohexanecarboxamide derived from 4-azatetracyclo[5.3.2.02,6.08,10]dodec-11-ene displayed low nanomolar inhibition of 11β-HSD1. In continuation of our efforts to discover potent and selective 11β-HSD1 inhibitors, herein we explored several replacements for the cyclohexane ring. Some derivatives exhibited potent inhibitory activity against human 11β-HSD1, although with low selectivity over the isoenzyme 11β-HSD2, and poor microsomal stability

Options for the Delivery of Intermittent Preventive Treatment for Malaria to Children: A Community Randomised Trial

Intermittent preventive treatment for malaria in children (IPTc) is a promising new intervention for the prevention of malaria but its delivery is a challenge. We have evaluated the coverage of IPTc that can be achieved by two different delivery systems in Ghana.IPTc was delivered by volunteers in six villages (community-based arm) and by health workers at health centres or at Expanded Programme on Immunisation outreach clinics (facility based) in another six communities. The villages were selected randomly and drugs were administered in May, June, September and October 2006. The first dose of a three-dose regimen of amodiaquine plus sulphadoxine-pyrimethamine was administered under supervision to 3-59 month-old children (n = 964) in the 12 study villages; doses for days 2 and 3 were given to parents/guardians to administer at home.The proportion of children who received at least the first dose of 3 or more courses of IPTc was slightly higher in the community based arm (90.5% vs 86.6%; p = 0.059). Completion of the three dose regimen was high and similar with both delivery systems (91.6% and 91.7% respectively).Seasonal IPTc delivered through community-based or facility-based systems can achieve a high coverage rate with the support and supervision of the district health management team. However, in order to maximise the impact of IPTc, both delivery systems may be needed in some settings.ClinicalTrials.gov NCT00119132

Oakleaf: an S locus-linked mutation of Primula vulgaris that affects leaf and flower development

•In Primula vulgaris outcrossing is promoted through reciprocal herkogamy with insect-mediated cross-pollination between pin and thrum form flowers. Development of heteromorphic flowers is coordinated by genes at the S locus. To underpin construction of a genetic map facilitating isolation of these S locus genes, we have characterised Oakleaf, a novel S locus-linked mutant phenotype. •We combine phenotypic observation of flower and leaf development, with classical genetic analysis and next-generation sequencing to address the molecular basis of Oakleaf. •Oakleaf is a dominant mutation that affects both leaf and flower development; plants produce distinctive lobed leaves, with occasional ectopic meristems on the veins. This phenotype is reminiscent of overexpression of Class I KNOX-homeodomain transcription factors. We describe the structure and expression of all eight P. vulgaris PvKNOX genes in both wild-type and Oakleaf plants, and present comparative transcriptome analysis of leaves and flowers from Oakleaf and wild-type plants. •Oakleaf provides a new phenotypic marker for genetic analysis of the Primula S locus. We show that none of the Class I PvKNOX genes are strongly upregulated in Oakleaf leaves and flowers, and identify cohorts of 507 upregulated and 314 downregulated genes in the Oakleaf mutant

ARLIS/NA Oral History for Distinguished Service Award Winners, Margaret Webster and Ted Goodman

Distinguished Service Award winners Margaret Webster (2010) and Ted Goodman (2012) interviewed by Janis Ekdahl on January 20, 2017. Both are former board members. The two discuss their careers in librarianship, talking about the rise of MARC and the relationship between ARLIS/NA and the Visual Resources Association (VRA), the creation of VRA Core and Getty AAT, and dancing with Sherman Clarke at annual conferences

Integration of genetic and physical maps of the Primula vulgaris S locus and localization by chromosome in situ hybridization

•Heteromorphic flower development in Primula is controlled by the S locus. The S locus genes, which control anther position, pistil length and pollen size in pin and thrum flowers, have not yet been characterized. We have integrated S-linked genes, marker sequences and mutant phenotypes to create a map of the P. vulgaris S locus region that will facilitate the identification of key S locus genes. We have generated, sequenced and annotated BAC sequences spanning the S locus, and identified its chromosomal location. •We have employed a combination of classical genetics and three-point crosses with molecular genetic analysis of recombinants to generate the map. We have characterized this region by Illumina sequencing and bioinformatic analysis, together with chromosome in situ hybridization. •We present an integrated genetic and physical map across the P. vulgaris S locus flanked by phenotypic and DNA sequence markers. BAC contigs encompass a 1.5-Mb genomic region with 1 Mb of sequence containing 82 S-linked genes anchored to overlapping BACs. The S locus is located close to the centromere of the largest metacentric chromosome pair. •These data will facilitate the identification of the genes that orchestrate heterostyly in Primula and enable evolutionary analyses of the S locus

The Valley Library Reference Collection : a white paper exploring future options

The Valley Library Reference Collection is under-utilized, occupies valuable physical space, and represents a significant investment in collection funds. As reference resources are available electronically, we have not effectively shaped our print or digital reference collection. The physical collection ages as we cancel reference continuations without replacing them with electronic sources. We are at a point where an objective conversation on the identify and use of the current reference collection is needed.Keywords: collection, reference, electronic reference sources, assessment, print reference source