An ecosystem-based job-creation engine fuelled by technology entrepreneurs

Job creation is at the centre of the rationale provided by governments and publicly funded organizations for investing in services purported to support entrepreneurs to launch and grow technology startups. However, little is known about how to design and build the engines that convert these publicly funded services into jobs in a region. In this article, we argue that the architecture of a job-creation engine fuelled by technology entrepreneurs is important and that it should be made visible to the stakeholders of a regional venture system. The manner in which the components of a job-creation engine are organized and integrated determines the effectiveness and efficiency of the conversion of public funds into jobs. Making visible the architecture of a job-creation engine enables individuals and organizations to: i) better understand the link between the investment made to service technology entrepreneurs and systematic job creation; ii) utilize the regional venture system more effectively; and iii) set the performance benchmark for capability improvement and rapid adjustment to environmental changes. The experience gained from operating Lead To Win since 2009 is used to describe the architecture of a job-creation engine fuelled by technology entrepreneurs that operate in Canada’s Capital Region. Lead To Win is an ecosystem designed to help a technology venture generate sufficient revenue to create six or more knowledge jobs in the region within three years of inception

Evaluation of polygenic determinants of non-alcoholic fatty liver disease (NAFLD) by a candidate genes resequencing strategy

NAFLD is a polygenic condition but the individual and cumulative contribution of identified genes remains to be established. To get additional insight into the genetic architecture of NAFLD, GWAS-identified GCKR, PPP1R3B, NCAN, LYPLAL1 and TM6SF2 genes were resequenced by next generation sequencing in a cohort of 218 NAFLD subjects and 227 controls, where PNPLA3 rs738409 and MBOAT7 rs641738 genotypes were also obtained. A total of 168 sequence variants were detected and 47 were annotated as functional. When all functional variants within each gene were considered, only those in TM6SF2 accumulate in NAFLD subjects compared to controls (P = 0.04). Among individual variants, rs1260326 in GCKR and rs641738 in MBOAT7 (recessive), rs58542926 in TM6SF2 and rs738409 in PNPLA3 (dominant) emerged as associated to NAFLD, with PNPLA3 rs738409 being the strongest predictor (OR 3.12, 95% CI, 1.8-5.5, P 0.28 was associated with a 3-fold increased risk of NAFLD. Interestingly, rs61756425 in PPP1R3B and rs641738 in MBOAT7 genes were predictors of NAFLD severity. Overall, TM6SF2, GCKR, PNPLA3 and MBOAT7 were confirmed to be associated with NAFLD and a score based on these genes was highly predictive of this condition. In addition, PPP1R3B and MBOAT7 might influence NAFLD severity

Designers' impressions of direct contact between product designers and champions of innovation

Suppliers of telecommunications and computer equipment, as well as other firms operating in rapidly changing environments, rely increasingly on their product designers for the formulation of opportunities for innovative new products-those that are more than simple refinements or extensions of established designs. This contrasts with the traditional use of designers to translate opportunities into products with specific properties and features only after they have been formulated by marketing and product managers. In this article, Antonio Bailetti and Paul Guild report on preliminary findings of a study undertaken by a leading world-wide supplier of telecommunications equipment to improve search methods leading to the formulation of opportunities for innovative new products. The implementation of a search method that relied upon direct contact between multidisciplinary teams with carefully selected sources of outside knowledge provided the setting for the study. Reported are 40 designers' impressions of the benefits derived from face-to-face exposure to external champions of innovation; the relationship between the characteristics of the sites that had been visited and the designers' perceptions of usefulness of the information acquired from the visits; and the differences in visiting and non-visiting designers' perceptions of the visits. The study is exploratory in nature and draws attention to the fact that more effort should be spent on examining how designers can best participate in the opportunity formulation process

A method for projects seeking to merge technical advancements with potential markets

Abstract The authors discuss a method for merging the results of technical advancements with potential markets during the formulation phase of innovative product development. The method emphasizes direct contact with end‐user organisations by multidisciplinary teams, the selection of champions of innovation as the source of useful and relevant insights, and a multi‐stage discipline to produce operational definitions of new product opportunities. For people responsible for managing technical activity, the paper offers guidelines for the planning and implementation of search methods, insight generation and specification of innovative products. Copyrigh

Metabolismo lipidico, stato degli antiossidanti e percezioni sensoriali nelle carni di suini alimentati con fitoderivati (Origanum vulgare L. e/o Rosmarinus officinalis)

In this study the effect of diets supplemented with extracts of oregano and/or rosemary (Origanum vulgare L. and/or Rosmarinus officinalis L.) on lipid metabolism, antioxidant status and sensory perceptions in meat was investigated in fattening pig. Eighty pigs were divided into five dietary groups (n.16/each identified as: control, C; 2: foil, F; 3: foil + 0.2% oregano, O; 4: foil + 0, 2% rosemary, R and 5: foil + 0.1% + 0.1% oregano, rosemary, OR). Blood samples were drawn from jugular vein after about 15 days of adaptation to the new diet and at the end of the finishing period (160 kg) Samples were used to determine the concentrations of cholesterol, triglycerides, b-hydroxy-butyrate, free fatty acids, the total antioxidant power and reactive metabolites oxygen. Sensory analysis was carried out on meat samples with the test ‘Duo-Trio Test’ and Ordering test on the basis of Preference (ISO 8587:2006). Integration with phyto derivates did not result in significant changes in the blood parameters investigated, while from the point of view of sensory analysis, the presence of oregano was somehow ‘felt’ so that the group of pigs supplemented with oregano have always been recognized as different from the control in terms of texture and flavor

Deep re-sequencing of 9 type 2 diabetes GWAS loci by comparison of extremes of dynamic indices of insulin secrection

Background and aims: The susceptibility genes for Type 2 Diabetes (T2D) identified so far are mainly involved in beta-cell function. To this point, Genome-Wide Association Studies (GWAS) have identified a large number of loci. Despite this large number, the major part of T2D inheritance is still uncovered.\ud This missing heritability might be explained by multiple, low-frequency variants that are not captured by GWAS. A powerful approach to highlight causal variants is to deep re-sequence candidate genes. To enhance the probability to highlight causal or protective variants together with the appropriate statistical power, we aimed to identify by Next Generation Sequencing (NGS) lowfrequency variants in GWAS loci for T2D, searching for primary defects in beta-cell insulin secretion. For this, we applied a two stage study design: Stage 1, deep re-sequencing of coding and flanking regions of 9 candidate genes that reach GWAS significance (p<10-8), in individuals selected from the extremes of insulin secretion, adjusted for insulin resistance, i.e. Disposition Index (DI); Stage 2, confirmation of the association by genotyping the variants differently distributed between the two extremes of insulin secretion in larger and independent groups of Italian adults and children (N=3130). Materials and methods: In a large population, very well characterized from OGTT, measures of insulin secretion and resistance have been calculated, including insulinogenic index (IGI30), ISI (insulin-sensitivity index), and DI (IGI30xISI). NGS was performed on MiSeq system (Illumina) with TruSeq Custom Amplicon approach. Variants are investigated by proper bioinformatics tools. Discovered variants will be genotyped by Real-Time PCR or by suitable methods such as SNP array and genotyping by sequencing. Results: We sequenced 383 subjects from the discovery sample. Preliminary results show more than 1500 variants in this sample. Bioinformatics tools predict that at least 122 of them may have a functional effect on protein, being missense or nonsense. A small but relevant part of passing-filter variants seems to be newly discovered (no rs) or to presumptively affect protein function. We then searched for a different distribution of all the infrequent variants within the two extremes of DI. Variants in one of the genes, ADAMTS9, were significantly associated with the higher extreme (>80%) of DI distribution (OR= 1.30 p=0.03). A similar trend was observed for four of the 9 candidate genes. Multivariate analyses showed that carriers of one o more variants have an OR= 9.06 (1.73-47.42) p=0.009 and OR= 8.52 (1.32-55.01) p=0.024 respectively, to be in the >80% extreme of DI. Conclusion: The next stage involves the in-depth analysis of all the variants discovered, evaluating distribution, frequency, and possible function, together with the replication studies in large cohorts to confirm the association with altered insulin secretion. We expect that this study will deliver several results: from confirmatory gene association to newer T2D associated polymorphisms, to possible new insights into potential biological mechanisms influencing T2D pathogenesis. Supported by: fellowship granted by the Italian Diabete Ricerca Foundation and MSD Italy Disclosure: D. Bailetti: Grants; fellowship granted by the Italian Diabete Ricerca Foundation and Merck Sharp & Dohme Ital

Deep re-sequencing of 9 type 2 diabetes GWAS loci by comparison of extremes of dynamic indices of insulin secrection

Background and aims: The susceptibility genes for Type 2 Diabetes (T2D) identified so far are mainly involved in beta-cell function. To this point, Genome-Wide Association Studies (GWAS) have identified a large number of loci. Despite this large number, the major part of T2D inheritance is still uncovered.\ud This missing heritability might be explained by multiple, low-frequency variants that are not captured by GWAS. A powerful approach to highlight causal variants is to deep re-sequence candidate genes. To enhance the probability to highlight causal or protective variants together with the appropriate statistical power, we aimed to identify by Next Generation Sequencing (NGS) lowfrequency variants in GWAS loci for T2D, searching for primary defects in beta-cell insulin secretion. For this, we applied a two stage study design: Stage 1, deep re-sequencing of coding and flanking regions of 9 candidate genes that reach GWAS significance (p<10-8), in individuals selected from the extremes of insulin secretion, adjusted for insulin resistance, i.e. Disposition Index (DI); Stage 2, confirmation of the association by genotyping the variants differently distributed between the two extremes of insulin secretion in larger and independent groups of Italian adults and children (N=3130). Materials and methods: In a large population, very well characterized from OGTT, measures of insulin secretion and resistance have been calculated, including insulinogenic index (IGI30), ISI (insulin-sensitivity index), and DI (IGI30xISI). NGS was performed on MiSeq system (Illumina) with TruSeq Custom Amplicon approach. Variants are investigated by proper bioinformatics tools. Discovered variants will be genotyped by Real-Time PCR or by suitable methods such as SNP array and genotyping by sequencing. Results: We sequenced 383 subjects from the discovery sample. Preliminary results show more than 1500 variants in this sample. Bioinformatics tools predict that at least 122 of them may have a functional effect on protein, being missense or nonsense. A small but relevant part of passing-filter variants seems to be newly discovered (no rs) or to presumptively affect protein function. We then searched for a different distribution of all the infrequent variants within the two extremes of DI. Variants in one of the genes, ADAMTS9, were significantly associated with the higher extreme (>80%) of DI distribution (OR= 1.30 p=0.03). A similar trend was observed for four of the 9 candidate genes. Multivariate analyses showed that carriers of one o more variants have an OR= 9.06 (1.73-47.42) p=0.009 and OR= 8.52 (1.32-55.01) p=0.024 respectively, to be in the >80% extreme of DI. Conclusion: The next stage involves the in-depth analysis of all the variants discovered, evaluating distribution, frequency, and possible function, together with the replication studies in large cohorts to confirm the association with altered insulin secretion. We expect that this study will deliver several results: from confirmatory gene association to newer T2D associated polymorphisms, to possible new insights into potential biological mechanisms influencing T2D pathogenesis. Supported by: fellowship granted by the Italian Diabete Ricerca Foundation and MSD Italy Disclosure: D. Bailetti: Grants; fellowship granted by the Italian Diabete Ricerca Foundation and Merck Sharp & Dohme Ital

The rs45454496 (E1813K) variant in the adiposity gene ANK2 doesn't associate with obesity in Southern European subjects

Recently ANK2, encoding ankyrin-B (AnkB), has been proposed as an obesity susceptibility gene. AnKB negatively regulates the expression of glucose transporter 4 (GLUT4) in adipocytes, and it has been hypothesized that functional alterations of AnkB may determine the persistence of GLUT4 on the cell surface, increasing glucose transport in adipocytes. Adipose tissue-specific AnkB-KO mice develop obesity and progressive pancreatic islet dysfunction with age or high-fat diet. AnkB-deficient adipocytes exhibit increased lipid accumulation associated with increased glucose uptake and impaired endocytosis of GLUT4. Functional alterations have been observed in ANK2 gene in European Americans and African Americans and have been proposed as candidates to contribute to obesity susceptibility in humans. Considering that variants of ANK2 gene were previously observed in subjects of American and African American ethnicity, and that these variants were never studied in association with obesity, we performed a genetic association analysis with obesity in a cohort of Southern European subjects. For this study 1900 Italian subjects with body mass index (BMI) between 16 and 91 were selected. All subjects underwent clinical examination, anthropometric measurements and routine laboratory tests. The SNPs rs45454496 (E1813K) and rs35530544 (L1622I) have been studied in DNAs by Eco TM Real-Time PCR System by Illumina. Among the 1900 subjects we identified 15 (frequency 0.7%) heterozygous subjects for the rs45454496 variant and no homozygous subject. The observed frequency in our population is more than double that observed in other populations of European origin (0.7% vs 0.3%, p = 0.3). We then analysed the association between this polymorphism and clinical and biochemical characteristics. Carriers of the mutation showed no significantly differences compared to wild-type subjects in any of the parameters examined. Population stratification by BMI showed a random distribution of the rs45454496 variant according to weight. Also, population stratification based on glycaemic alterations showed no association of the rs45454496 variant with categories of glucose metabolism. Finally, we analysed the study cohort for the rs35530544, but we did not observe any subject carrying the variant in an initial sample of 840 patients. In conclusion, we observed that the rs45454496 (E1813K) variant of ANK2 gene, although showing a higher frequency in our Southern European population (0.7%) than the frequencies reported in other populations of European origin, in the analysed sample does not seem to have effects on clinical and metabolic alterations