Overcoming Customer Dependency - A Case Study of Small Consumer Food Producers in Northern Ireland

Dependency on a small number of customer puts intense pressure on suppliers' profit margin and, in slow growing markets, limits their ability to grow. using stragtegic benchmarking information, a group of Northern Ireland consumer food producer are shown, depsite slow market growth and higher than averge customer dependency, to have increased market share while maintaining aboe vergate proitability. examination of the business strategic and develoment activites of the consumer food firms,and comparble information for other small food prodcuers in Ireland, suggests and emphasiss on cost-reduction and new prodcut development. A comparision of the productivity and prodcut range of the consuer food firms provides evidence of the success of these strategic. This suggests that even a relatively weak market situations, charactrised by dependency on a small number of customers, can be over come by effective and appropriate business strategy.

SGK1 activity in Na+ absorbing airway epithelial cells monitored by assaying NDRG1-Thr(346/356/366) phosphorylation

Studies of HeLa cells and serum- and glucocorticoid-regulated kinase 1 (SGK1) knockout mice identified threonine residues in the n-myc downstream-regulated gene 1 protein (NDRG1-Thr(346/356/366)) that are phosphorylated by SGK1 but not by related kinases (Murray et al., Biochem J 385:1-12, 2005). We have, therefore, monitored the phosphorylation of NDRG1-Thr(346/356/366) in order to explore the changes in SGK1 activity associated with the induction and regulation of the glucocorticoid-dependent Na+ conductance (G (Na)) in human airway epithelial cells. Transient expression of active (SGK1-S422D) and inactive (SGK1-K127A) SGK1 mutants confirmed that activating SGK1 stimulates NDRG1-Thr(346/356/366) phosphorylation. Although G (Na) is negligible in hormone-deprived cells, these cells displayed basal SGK1 activity that was sensitive to LY294002, an inhibitor of 3-phosphatidylinositol phosphate kinase (PI3K). Dexamethasone (0.2 mu M) acutely activated SGK1 and the peak of this response (2-3 h) coincided with the induction of G (Na), and both responses were PI3K-dependent. While these data suggest that SGK1 might mediate the rise in G (Na), transient expression of the inactive SGK1-K127A mutant did not affect the hormonal induction of G (Na) but did suppress the activation of SGK1. Dexamethasone-treated cells grown on permeable supports formed confluent epithelial sheets that generated short circuit current due to electrogenic Na+ absorption. Forskolin and insulin both stimulated this current and the response to insulin, but not forskolin, was LY294002-sensitive and associated with the activation of SGK1. While these data suggest that SGK1 is involved in the control of G (Na), its role may be minor, which could explain why sgk1 knockout has different effects upon different tissues.

The biology and ecology of the ocean sunfish Mola mola: a review of current knowledge and future research perspectives

Relatively little is known about the biology and ecology of the world's largest (heaviest) bony fish, the ocean sunfish Mola mola, despite its worldwide occurrence in temperate and tropical seas. Studies are now emerging that require many common perceptions about sunfish behaviour and ecology to be re-examined. Indeed, the long-held view that ocean sunfish are an inactive, passively drifting species seems to be entirely misplaced. Technological advances in marine telemetry are revealing distinct behavioural patterns and protracted seasonal movements. Extensive forays by ocean sunfish into the deep ocean have been documented and broad-scale surveys, together with molecular and laboratory based techniques, are addressing the connectivity and trophic role of these animals. These emerging molecular and movement studies suggest that local distinct populations may be prone to depletion through bycatch in commercial fisheries. Rising interest in ocean sunfish, highlighted by the increase in recent publications, warrants a thorough review of the biology and ecology of this species. Here we review the taxonomy, morphology, geography, diet, locomotion, vision, movements, foraging ecology, reproduction and species interactions of M. mola. We present a summary of current conservation issues and suggest methods for addressing fundamental gaps in our knowledge.

A Framework for the Evaluation of Digital Musical Instruments

At the outset of a discussion of evaluating digital musical instruments, that is to say instruments whose sound generators are digital and separable though not necessarily separate from their control interfaces (Malloch, 2006), it is reasonable to ask what the term evaluation in this context really means. After all, there may be many perspectives from which to view the effectiveness or otherwise of the instruments we build. For most performers, performance on an instrument becomes a means of evaluating how well it functions in the context of live music making, and their measure of success is the response of the audience to their performance. Audiences evaluate performances on the basis of how engaged they feel they have been by what they have seen and heard. When questioned, they are likely to describe good performances as “exciting,” “skillful,” “musical.” Bad performances are “boring,” and those which are marred by technical malfunction are often dismissed out of hand. If performance is considered to be a valid means of evaluating a musical instrument, then it follows that, for the field of DMI design, a much broader definition of the term “evaluation” than that typically used in human-computer interaction (HCI) is required to reflect the fact that there are a number of stakeholders involved in the design and evaluation of DMIs. In addition to players and audiences, there are also composers, instrument builders, component manufacturers, and perhaps even customers, each of whom will have a different concept of what is meant by “evaluation.”

Contractile and vasorelaxant effects of hydrogen sulfide and its biosynthesis in the human internal mammary artery

This study aimed to test these hypotheses: cystathionine gamma-lyase (CSE) is expressed in a human artery, it generates hydrogen sulfide (H2S), and H2S relaxes a human artery. H2S is produced endogenously in rat arteries from cysteine by CSE. Endogenously produced H2S dilates rat resistance arteries. Although CSE is expressed in rat arteries, its presence in human blood vessels has not been described. In this study, we showed that both CSE mRNA, determined by reverse transcription-polymerase chain reaction, and CSE protein, determined by Western blotting, apparently occur in the human internal mammary artery (internal thoracic artery). Artery homogenates converted cysteine to H2S, and the H2S production was inhibited by DL-propargylglycine, an inhibitor of CSE. We also showed that H2S relaxes phenylephrine-precontracted human internal mammary artery at higher concentrations but produces contraction at low concentrations. The latter contractions are stronger in acetylcholine-prerelaxed arteries, suggesting inhibition of nitric oxide action. The relaxation is partially blocked by glibenclamide, an inhibitor of K-ATP channels. The present results indicate that CSE protein is expressed in human arteries, that human arteries synthesize H2S, and that higher concentrations of H2S relax human arteries, in part by opening K-ATP channels. Low concentrations of H2S contract the human internal mammary artery, possibly by reacting with nitric oxide to form an inactive nitrosothiol. The possibility that CSE, and the H2S it generates, together play a physiological role in regulating the diameter of arteries in humans, as has been demonstrated in rats, should be considered.

RUNX3, a novel tumor suppressor, is frequently inactivated in gastric cancer by protein mislocalization

Loss of RUNX3 expression is suggested to be causally related to gastric cancer as 45% to 60% of gastric cancers do not express RUNX3 mainly due to hypermethylation of the RUNX3 promoter. Here, we examined for other defects in the properties of RUNX3 in gastric cancers that express RUNX3. Ninety-seven gastric cancer tumor specimens and 21 gastric cancer cell lines were examined by immunohistochemistry using novel anti-RUNX3 monoclonal antibodies. In normal gastric mucosa, RUNX3 was expressed most strongly in the nuclei of chief cells as well as in surface epithelial cells. In chief cells, a significant portion of the protein was also found in the cytoplasm. RUNX3 was not detectable in 43 of 97 (44%) cases of gastric cancers tested and a further 38% showed exclusive cytoplasmic localization, whereas only 18% showed nuclear localization. Evidence is presented suggesting that transforming growth factor-beta is an inducer of nuclear translocation of RUNX3, and RUNX3 in the cytoplasm of cancer cells is inactive as a tumor suppressor. RUNX3 was found to be inactive in 82% of gastric cancers through either gene silencing or protein mislocalization to the cytoplasm. In addition to the deregulation of mechanisms controlling gene expression, there would also seem to be at least one other mechanism controlling nuclear translocation of RUNX3 that is impaired frequently in gastric cancer.

Use of synthetic peptides to locate novel integrin alpha(2)beta(1)-binding motifs in human collagen III

A set of 57 synthetic peptides encompassing the entire triple-helical domain of human collagen III was used to locate binding sites for the collagen-binding integrin alpha(2)beta(1). The capacity of the peptides to support Mg2+-dependent binding of several integrin preparations was examined. Wild-type integrins (recombinant alpha(2) I-domain, alpha(2)beta(1) purified from platelet membranes, and recombinant soluble alpha(2)beta(1) expressed as an alpha(2)-Fos/beta(1)-Jun heterodimer) bound well to only three peptides, two containing GXX'GER motifs (GROGER and GMOGER, where O is hydroxyproline) and one containing two adjacent GXX'GEN motifs (GLKGEN and GLOGEN). Two mutant alpha(2) I-domains were tested: the inactive T221A mutant, which recognized no peptides, and the constitutively active E318W mutant, which bound a larger subset of peptides. Adhesion of activated human platelets to GER-containing peptides was greater than that of resting platelets, and HT1080 cells bound well to more of the peptides compared with platelets. Binding of cells and recombinant proteins was abolished by anti-alpha(2) monoclonal antibody 6F1 and by chelation of Mg2+. We describe two novel high affinity integrin-binding motifs in human collagen III (GROGER and GLOGEN) and a third motif (GLKGEN) that displays intermediate activity. Each motif was verified using shorter synthetic peptides.

Methadone as Social Control: Institutionalized Stigma and the Prospect of Recovery

Methadone maintenance treatment (MMT) is an intervention used to treat opioid (heroin) dependence. Several investigators have found that MMT is effective in reducing heroin use and other behaviors; however, a disproportionate number of MMT clients leave treatment prematurely. Moreover, MMT outcome variables are often limited in terms of their measurement. Utilizing an integrated theoretical framework of social control and stigma, we focused on the experiences of methadone maintenance from the perspective of clients. We pooled interview data from four qualitative studies in two jurisdictions and found linkages between social control and institutional stigma that serve to reinforce "addict" identities, expose undeserving customers to the public gaze, and encourage clients to be passive recipients of treatment. We discuss the implications for recovery and suggest recommendations for change.

Effect of target slaughter weight on production efficiency, carcass traits and behaviour of restrictively-fed gilts and intact male finisher pigs

The effect of 3 slaughter weights (85.95 or 105 kg) on performance and carcass traits of 481 pigs in single-gender groups of 13 (18 groups of gilts and 19 groups of intact males) was evaluated. Pigs (39.5 +/- 3.3 kg) were fed a liquid diet 3 times daily in a long trough. The behaviour of pigs slaughtered at 105 kg was recorded at 50, 60 and 70 days after the start of the experiment (5 groups of gilts and 4 groups of intact males). Behaviour (active, inactive, feeding) and posture (standing, lying, dog-sitting) of all pigs was recorded at 5-min intervals for 30 min prior to and 1 h after each feeding event. Slaughtering pigs at 95 kg and 105 kg delayed production by 7 and 16 days, respectively, compared to slaughtering at 85 kg (P0.05). Muscle depth increased with increasing slaughter weight (P

Profiling of the BRCA1 transcriptome through microarray and ChIP-chip analysis

A role for BRCA1 in the direct and indirect regulation of transcription is well established. However, a comprehensive view of the degree to which BRCA1 impacts transcriptional regulation on a genome-wide level has not been defined. We performed genome-wide expression profiling and ChIP-chip analysis, comparison of which revealed that although BRCA1 depletion results in transcriptional changes in 1294 genes, only 44 of these are promoter bound by BRCA1. However, 27 of these transcripts were linked to transcriptional regulation possibly explaining the large number of indirect transcriptional changes observed by microarray analysis. We show that no specific consensus sequence exists for BRCA1 DNA binding but rather demonstrate the presence of a number of known and novel transcription factor (TF)- binding sites commonly found on BRCA1 bound promoters. Co-immunoprecipitations confirmed that BRCA1 interacts with a number of these TFs including AP2-a, PAX2 and ZF5. Finally, we show that BRCA1 is bound to a subset of promoters of genes that are not altered by BRCA1 loss, but are transcriptionally regulated in a BRCA1-dependent manner upon DNA damage. These data suggest a model, whereby BRCA1 is present on defined promoters as part of an inactive complex poised to respond to various genotoxic stimuli. © The Author(s) 2011. Published by Oxford University Press.

The effect of increasing dietary fibre and the provision of straw racks on the welfare of sows housed in small static groups

This study assessed the effects of increasing dietary fibre levels in concentrate rations and providing access to straw in racks on the welfare of pregnant sows housed in small static groups. In a 2 x 2 factorial design experiment, 128 Large White x Landrace pregnant sows were offered one of two diets: (i) High fibre diet with 9% crude fibre, or (ii) Control diet with 4.5% CF, and one of two levels of access to a foraging substrate: (i) access to straw in racks or (ii) no straw. The study was replicated eight times using groups of four sows, and treatment periods lasted four weeks. Sows were housed in pens with voluntary cubicles and a slatted exercise area and were offered a wet diet twice a day. Back-fat levels were measured before sows were mixed into groups at 28 days post partum, and four weeks later. Aggressive interactions were recorded on the day of mixing, and injury scores were recorded one week post mixing. Scan sampling was used to collect data on general activity, posture and location of the sows, and on sham-chewing and bar-biting behaviours across the treatment period. In addition, detailed focal observations were carried out on all sows across the treatment period. Straw usage was also recorded. There were no treatment effects on changes in back-fat levels over the treatment period. Treatments had no effect on post-mixing aggression or on injury scores. However, focal observations showed that sows with access to straw were involved in fewer bouts of head-thrusting over the treatment period. Control diet sows spent more time inactive than sows on the high fibre diet, however high fibre diet sows spent more time lying with eyes closed than sows on the control diet. Sows on the high fibre diet with access to straw showed less sham-chewing and bar-biting behaviour than sows in other treatments. These results show that although a diet containing 9% crude fibre promoted resting behaviour, it was necessary to combine it with access to straw to reduce stereotypic behaviour of sows in small static groups.

The synthesis, characterisation and reactivity of 2-phosphanylethylcyclopentadienyl complexes of cobalt, rhodium and iridium

2-Phosphanylethylcyclopentadienyl lithium compounds, Li[C5R'(4)(CH2)(2)PR2] (R = Et, R' = H or Me, R = Ph, R' = Me), have been prepared from the reaction of spirohydrocarbons C5R'(4)(C2H4) with LiPR2. C5Et4HSiMe2CH2PMe2, was prepared from reaction of Li[C5Et4] with Me2SiCl2 followed by Me2PCH2Li. The lithium salts were reacted with [RhCl(CO)2]2,[IrCl(CO)3] or [Co-2(CO)(8)] to give [M(C5R'(4)(CH2) 2PR2)(CO)] (M = Rh, R = Et, R' = H or Me, R= Ph, R' = Me; M = Ir or Co, R = Et, R' = Me), which have been fully characterised, in many cases crystallographically as monomers with coordination of the phosphorus atom and the cyclopentadienyl ring. The values of nu(CO) for these complexes are usually lower than those for the analogous complexes without the bridge between the cyclopentadienyl ring and the phosphine, the exception being [Rh(Cp'(CH2)(2)PEt2)(CO)] (Cp' = C5Me4), the most electron rich of the complexes. [Rh(C5Et4SiMe2CH2PMe2)(CO)] may be a dimer. [Co-2(CO)(8)] reacts with C5H5(CH2)(2)PEt2 or C5Et4HSiMe2CH2PMe2 (L) to give binuclear complexes of the form [Co-2(CO)(6)L-2] with almost linear PCoCoP skeletons. [Rh(Cp'(CH2)(2)PEt2)(CO)] and [Rh(Cp'(CH2)(2)PPh2)(CO)] are active for methanol carbonylation at 150 degrees C and 27 bar CO, with the rate using [Rh(Cp'(CH2)(2)PPh2)(CO)] (0.81 mol dm(-3) h(-1)) being higher than that for [RhI2(CO)(2)](-) (0.64 mol dm(-3) h(-1)). The most electron rich complex, [Rh(Cp'(CH2)(2)PEt2)(CO)] (0.38 mol dm(-3) h(-1)) gave a comparable rate to [Cp*Rh(PEt3)(CO)] (0.30 mol dm(-3) h(-1)), which was unstable towards oxidation of the phosphine. [Rh(Cp'(CH2)(2)PEt2)I-2], which is inactive for methanol carbonylation, was isolated after the methanol carbonylation reaction using [Rh(Cp'(CH2)(2)PEt2)(CO)].

Secreted cysteine proteases of the carcinogenic liver fluke, Opisthorchis viverrini: Regulation of cathepsin F activation by autocatalysis and trans-processing by cathepsin B

Opisthorchis viverrini is an important helminth pathogen of humans that is endemic in Thailand and Laos. Adult flukes reside within host bile ducts and feed on epithelial tissue and blood cells. Chronic opisthorchiasis is associated with severe hepatobiliary diseases such as cholangiocarcinoma. Here we report that adult O. viverrini secrete two major cysteine proteases: cathepsin F (Ov-CF-1) and cathepsin B1 (Ov-CB-1). Ov-CF-1 is secreted as an inactive zymogen that autocatalytically processes and activates to a mature enzyme at pH 4.5 via an intermolecular cleavage at the prosegment-mature domain junction. Ov-CB-1 is also secreted as a zymogen but, in contrast to Ov-CF-1, is fully active against peptide and macromolecular substrates despite retaining the N-terminal prosegment. The active Ov-CB-1 zymogen was capable of trans-activating Ov-CF-1 by proteolytic removal of its prosegment at pH 5.5, a pH at which the Ov-CF-1 zymogen cannot autocatalytically activate. Both cathepsins hydrolyse human haemoglobin but their combined action more efficiently degrades haemoglobin to smaller peptides than each enzyme alone. Ov-CF-1 degraded extracellular matrix proteins more effectively than Ov-CB-1 at physiological pH. We propose that Ov-CB-1 regulates Ov-CF-1 activity and that both enzymes work together to degrade host tissue contributing to the development of liver fluke-associated cholangiocarcinoma.

THE EFFECT OF THE SULFOXIDE METABOLITE OF TRICLABENDAZOLE (FASINEX) ON THE TEGUMENT OF MATURE AND IMMATURE STAGES OF THE LIVER FLUKE, FASCIOLA-HEPATICA

The effects of the novel benzimidazole, triclabendazole (TCBZ) ('Fasinex', Ciba-Geigy), in its active sulphoxide metabolite form (TCBZ-SX), on the tegumental ultrastructure of Fasciola hepatica were determined in vitro by transmission electron microscopy (TEM), using both intact flukes and tissue-slice material. At a concentration of 15 mu g/ml, the tegument of the whole adult fluke showed ultrastructural changes only after prolonged time-periods, with vacuolation at the base of the syncytium and accumulation of T2 secretory bodies in the tegumental cells. At a concentration of 50 mu g/ml, with both whole flukes and tissue-slices, the tegument appeared extremely abnormal with accumulation of secretory bodies towards the base of the syncytium. With longer incubation times, the tegument was completely sloughed away and the tegumental cells became synthetically inactive. The tegument of the 3-week-old juvenile became progressively convoluted at the apex, while in the basal regions there was severe vacuolation. In the tegumental cells, there were accumulations of T1 secretory bodies. These results confirm TCBZ as a potent fasciolicide, being very effective in disrupting the fluke tegument. They may go some way to explain the mode of action of this important fasciolicide.

Structure-activity relationships of FMRFamide-related peptides contracting Schistosoma mansoni muscle

This study reports the potent myoactivity of flatworm FMRFamide-related peptides (FaRPs) on isolated muscle fibers of the human blood fluke, Schistosoma mansoni. The turbellarian peptides YIRFamide (EC50 4 eta M), GYIRFamide (EC50 1 eta M). and RYIRFamide (EC50 7 eta M), all induced muscle contraction more potently than the cestode FaRP GNFFRFamide (EC50 500 eta M). Using a series of synthetic analogs of the flatworm peptides YIRFamide, GYIRFamide and RYIRFamide, the structure-activity relationships of the muscle FaRP receptor were examined. With a few exceptions, each residue in YIRFamide is important in the maintenance of its myoactivity. Alanine scans resulted in peptides that were inactive (Ala(1), Ala(2), Ala(3) and Ala(4) YIRFamide; Ala(4) and Ala(5) RYIRFamide) or had much reduced potencies (Ala(1), Ala(2) and Ala(3) RYIRFamide). Substitution of the N-terminal (Tyr(1)) residue of YIRFamide with the non-aromatic residues Thr or Arg produced analogs with greatly reduced potency. Replacement of the N-terminal Tyr with aromatic amino acids resulted in myoactive peptides (FIRFamide, EC50 100 eta M; WIRFamide, EC50 0.5 eta M). The activity of YIRFamide analogs which possessed a Leu(2), Phe(2) or Met(2) residue (EC50's 10, 1 and 3 eta M, respectively) instead of Ile(2) was not significantly altered, whereas, YVRFamide had a greatly reduced (EC50 200 eta M) activity. Replacement of the Phe(4) with a Tyr(4) (YIRYamide) also greatly lowered potency. Truncated analogs were either inactive (FRFamide, YRFamide, HRFamide, RFamide, Famide) or had very low potency (IRFamide and MRFamide), with the exception of nLRFamide (EC50 20 eta M). YIRF free acid was inactive. In summary, these data show the general structural requirements of this schistosome muscle FaRP receptor to be similar, but not identical, to those of previously characterized molluscan FaRP receptors. (C) 1997 Elsevier Science Inc.