Abstract: The Windber Research Institute is an integrated high-throughput research center employing clinical, genomic and proteomic platforms to produce terabyte levels of data. We use biomedical informatics technologies to integrate all of these operations. This report includes information on a multi-year, multi-phase hybrid data warehouse project currently under development in the Institute. The purpose of the warehouse is to host the terabyte-level of internal experimentally generated data as well as data from public sources. We have previously reported on the phase I development, which integrated limited internal data sources and selected public databases. Currently, we are completing phase II development, which integrates our internal automated data sources and develops visualization tools to query across these data types. This paper summarizes our clinical and experimental operations, the data warehouse development, and the challenges we have faced. In phase III we plan to federate additional manual internal and public data sources and then to develop and adapt more data analysis and mining tools. We expect that the final implementation of the data warehouse will greatly facilitate biomedical informatics research.

Abstract: The turnip fly, Delia floralis Fallén (Diptera: Anthomyiidae) is an important insect pest of brassica vegetable crops in the holarctic region. Different populations have strongly varying temperature requirements for fly emergence, a challenge for accurate prediction of activity. This study focused on diapause development in one early and one late emerging phenotype. The physiological state after various treatments was deduced from emergence data. Our results showed a slow diapause progression at chilling conditions for both populations and diapause ended about 7 months after pupae were formed for the early population. For the late population held at 4°C diapause did not end, no matter how long the duration of chilling. These pupae required a period with elevated temperatures above 6°C to continue development. At constant non‐chilling conditions (18°C) from the time pupae were formed both populations completed diapause most rapidly. These results indicate that chilling delayed, rather than accelerated development and was not a prerequisite for diapause development. For post‐diapause, results indicated a linear relationship between rate of development and temperature within the range of 6–18°C and a theoretical base temperature for development of about 2°C for both populations. In conclusion, D. floralis pupae are in diapause throughout a long winter period, and delayed emergence of the late population appears to be caused by prolonged diapause regulated by a developmental temperature threshold. The study has added information on the biology of turnip fly populations, a prerequisite for improved pest control.

Abstract: The environmental risk assessment of the herbicide tolerant genetically modified oilseed rape MON 88302 (Reference EFSA/GMO/BE/2011/101) has been performed by the Panel on Genetically Modified Organisms (GMO) of the Norwegian Scientific Committee for Food Safety (VKM). VKM has been requested by the Norwegian Directorate for Nature Management and the Norwegian Food Safety Authority to issue a preliminary scientific opinion on the safety of the genetically modified oilseed rape MON 88302 (Unique identifier MON-88Ø2-9) for food and feed uses, import and processing, and submit relevant scientific comments or questions to EFSA on the application EFSA/GMOBE/2011/101.  The environmental risk assessment of the MON 88302 is based on information provided by the applicant in the application EFSA/GMO/BE/2011/101, and scientific comments from EFSA and other member states made available on the EFSA website GMO Extranet. The risk assessment also considered peer-reviewed scientific literature as relevant.   The VKM GMO Panel has evaluated MON 88302 with reference to its intended uses in the European Economic Area (EEA), and according to the principles described in the Norwegian Food Act, the Norwegian Gene Technology Act and regulations relating to impact assessment pursuant to the Gene Technology Act, Directive 2001/18/EC on the deliberate release into the environment of genetically modified organisms, and Regulation (EC) No 1829/2003 on genetically modified food and feed. The Norwegian Scientific Committee for Food Safety has also decided to take account of the appropriate principles described in the EFSA guidelines for the risk assessment of GM plants and derived food and feed (EFSA 2006, 2011a), the environmental risk assessment of GM plants (EFSA 2010), the selection of comparators for the risk assessment of GM plants (EFSA 2011b), and for the post-market environmental monitoring of GM plants (EFSA 2006, 2011c).  The scientific risk assessment of oilseed rape MON 88302 include molecular characterisation of the inserted DNA and expression of target proteins, comparative assessment of agronomic and phenotypic characteristics, unintended effects on plant fitness, potential for horizontal and vertical gene transfer, and evaluations of the post-market environmental plan. In line with its mandate, VKM emphasized that assessments of sustainable development, societal utility and ethical considerations, according to the Norwegian Gene Technology Act and Regulations relating to impact assessment pursuant to the Gene Technology Act, shall not be carried out by the Panel on Genetically Modified Organisms. The GMO Panel has therefore not considered possible health and environmental effects of cultivation and processing of oilseed rape MON 88302 outside the EU/EEA area. The genetically modified oilseed rape MON 88302 was developed to provide tolerance to the herbical active substance glyphosate by the introduction of a gene coding for the enzyme 5enolpyruvylshikimate-3-phosphate synthase (EPSPS) from Agrobacterium tumefaciens, strain CP4 (CP4 EPSPS). Glyphosate is a non-selective herbicide and is normally phytotoxic to a broad range of plants. Its mode of action occurs by binding to and inactivating the EPSPS protein, which is a key enzyme in the shikimate pathway that leads to the biosynthesis of the aromatic amino acids tyrosine, tryptophan and phenylalanine. The disruption of this pathway and the resulting inability to produce key amino acids prevents growth and ultimately leads to plant death.  Molecular characterization: The VKM Panel on Genetically Modified Organisms find the conclusion that no major section of the T-DNA plasmid backbone is inserted in MON88302 oilseed rape justified. We also find it justified that there is only one major T-DNA insert in MON88302.  Comparative assessment: Based on results from comparative analyses of data from field trials located at representative sites and environments in the USA, Canada and Chile, it is concluded that oilseed rape MON 88302 is agronomically and phenotypically equivalent to the conventional counterpart and commercial available reference varieties, with the exception of the herbicide tolerance conferred by the CP4 EPSPS protein. The field evaluations support a conclusion of no phenotypic changes indicative of increased plant weed/pest potential of MON 88302 compared to conventional oilseed rape. Furthermore, the results demonstrate that in-crop applications of glyphosate herbicide do not alter the phenotypic and agronomic characteristics of MON 88302 compared to conventional oilseed rape. Evaluations of environmental interactions between genetically modified oilseed rape MON 88302 and the biotic and abiotic environment, and studies of seed dormancy, seed germination, pollen morphology and viability indicates no unintended effects of the introduced trait on these characteristics in MON 88302 oilseed rape.  Environmental risk: Considering the scope of the application EFSA/GMO/BE/2011/101, excluding cultivation purposes, the environmental risk assessment is limited to exposure through accidental spillage of viable seeds of MON 88302 into the environment during transportation, storage, handling, processing and use of derived products. Oilseed rape is mainly a self-pollinating species, but has entomophilous flowers capable of both self- and cross-pollinating. Normally the level of outcrossing is about 30 %, but outcrossing frequencies up to 55 % are reported.  Several plant species related to oilseed rape that are either cultivated, occurs as weeds of cultivated and disturbed lands, or grow outside cultivation areas to which gene introgression from oilseed rape could be of concern. These are found both in the Brassica species complex and in related genera. A series of controlled crosses between oilseed rape and related taxa have been reported in the scientific literature. Because of a mismatch in the chromosome numbers most hybrids have a severely reduced fertility. Exceptions are hybrids obtained from crosses between oilseed rape and wild turnip (B. rapa ssp. campestris) and to a lesser extent, mustard greens (B.juncea), where spontaneously hybridising and transgene introgression under field conditions have been confirmed. Wild turnip is native to Norway and a common weed in arable lowlands. There is no evidence that the herbicide tolerant trait results in enhanced fitness, persistence or invasiveness of oilseed rape MON 88302, or hybridizing wild relatives, compared to conventional oilseed rape varieties, unless the plants are exposed to glyphosate-containing herbicides. However, accidental spillage and loss of viable seeds of MON 88302 during transport, storage, handling in the environment and processing into derived products is likely to take place over time, and the establishment of small populations of oilseed rape MON 88302 on locations where glyphosate is frequently applied to control weeds e.g. on railway tracks, cannot be excluded. Feral oilseed rape MON 88302 arising from spilled seed could theoretically pollinate conventional crop plants if the escaped populations are immediately adjacent to field crops, and shed seeds from cross-pollinated crop plants could emerge as GM volunteers in subsequent crops. However, both the occurrence of feral oilseed rape resulting from seed import spills and the introgression of genetic material from feral oilseed rape populations to wild populations are likely to be low in an import scenario. Apart from the glyphosate tolerance trait, the resulting progeny will not possess a higher fitness and will not be different from progeny arising from cross-fertilisation with conventional oilseed rape varieties. The VKM GMO Panel concludes that this route of gene flow would not introduce significant numbers of transgenic plants into agricultural areas or result in any environmental consequences in Norway. The environmental risk assessment will be completed and finalized by the VKM Panel on Genetically Modified Organisms when requested additional information from the applicant is available.

Abstract: In preparation for a legal implementation of EU-regulation 1829/2003, the Norwegian Scientific Committee for Food Safety (VKM) has been requested by the Norwegian Directorate for Nature Management to conduct final environmental risk assessments for all genetically modified organisms (GMOs) and products containing or consisting of GMOs that are authorized in the European Union under Directive 2001/18/EC or Regulation 1829/2003/EC. The request covers scope(s) relevant to the Gene Technology Act. The request does not cover GMOs that VKM already has conducted its final risk assessments on. However, the Directorate requests VKM to consider whether updates or other changes to earlier submitted assessments are necessary. MON810 notification C/F/95/12-02 is approved under Directive 90/220/EEC for cultivation, seed production, import and processing into feeding stuffs and industrial purposes since 22 April 1998 (Commission Decision 98/294/EC). In December 1997, food and food ingredients derived from the progeny of maize line MON810 were notified under Article 5 of Regulation (EC) No 258/97 on novel foods and novel food ingredients. In addition, existing food and feed products containing, consisting of or produced from MON810 were notified according to Articles 8 and 20 of Regulation (EC) No 1829/2003 and were placed in the Community Register in 2005.  Three applications for renewal of the authorisation for continued marketing of (1) existing food and food ingredients produced from MON810; (2) feed consisting of and/or containing maize MON810, and MON810 for feed use (including cultivation); and (3) food and feed additives, and feed materials produced from maize MON810 within the framework of Regulation (EC) No 1829/2003 were submitted in 2007.  Maize MON810 has previously been assessed by the VKM GMO Panel commissioned by the Norwegian Directorate for Nature Management in connection with the national finalisation of the procedure of the notification C/F/95/12/02 (VKM 2007a,b). In addition, MON810 has been evaluated by the VKM GMO Panel as a component of several stacked GM maize events (VKM 2005a,b,c, VKM 2007c, VKM 2008, VKM 2009, VKM 2012). Due to the publication of updated guidelines for environmental risk assessments of genetically modified plants and new scientific literature, the VKM GMO Panel has decided to deliver an updated environmental risk assessment of MON810. The environmental risk assessment of the maize MON810 is based on information provided by the applicant in the notification C/F/95/12/02 and application EFSA/GMO/RX/MON810, and scientific comments from EFSA and other member states made available on the EFSA website GMO Extranet. The risk assessment also considered other peer-reviewed scientific literature as relevant.   The VKM GMO Panel has evaluated MON810 with reference to its intended uses in the European Economic Area (EEA), and according to the principles described in the Norwegian Food Act, the Norwegian Gene Technology Act and regulations relating to impact assessment pursuant to the Gene Technology Act, Directive 2001/18/EC on the deliberate release into the environment of genetically modified organisms, and Regulation (EC) No 1829/2003 on genetically modified food and feed. The Norwegian Scientific Committee for Food Safety has also decided to take account of the appropriate principles described in the EFSA guidelines for the risk assessment of GM plants and derived food and feed (EFSA 2006, 2011a), the environmental risk assessment of GM plants (EFSA 2010), the selection of comparators for the risk assessment of GM plants (EFSA 2011b), and for the post-market environmental monitoring of GM plants (EFSA 2006, 2011c).  The scientific risk assessment of maize MON810 include molecular characterisation of the inserted DNA and expression of the target protein, comparative assessment of agronomic and phenotypic characteristics, unintended effects on plant fitness, potential for gene transfer, interactions between the GM plant and target and non-target organisms, effects on biogeochemical processes and evaluations of the post-market environmental plan. In line with its mandate, VKM emphasised that assessments of sustainable development, societal utility and ethical considerations, according to the Norwegian Gene Technology Act and Regulations relating to impact assessment pursuant to the Gene Technology Act, shall not be carried out by the Panel on Genetically Modified Organisms.  The genetically modified maize MON810 was developed to provide protection against certain lepidopteran target pests, including European corn borer (Ostrinia nubilalis) and species belonging to the genus Sesamia. Protection is achieved through expression in the plant of the insecticidal Cry protein, Cry1Ab, derived from Bacillus thuringiensis ssp. kurstaki, a common soil bacterium.   Molecular characterisation Appropriate analysis of the integration site including flanking sequences and bioinformatics analyses have been performed to analyse the construct integrated in the GM plant. Updated bioinformatics analyses revealed that one ORF shared sequence similarity to a putative HECT-ubiquitin ligase protein.  The VKM GMO Panel found no safety implications from the interruption of this gene sequence. Analyses of leaf, grains, whole plant tissue and pollen from the maize MON 810 demonstrated that the Cry1Ab protein is expressed at very low levels in all tissues tested and constitutes less than 0.001% of the fresh weight in each tissue. The cry1Ab gene is the only transgene expressed in line MON 810 and was expressed highest in the leaves. The stability of the genetic modification has been demonstrated over several generations. Event MON810 and the physical, chemical and functional characteristics of the proteins have previously been evaluated by The VKM Panel on Genetically Modified Organisms, and considered satisfactory (VKM 2007a,b). Comparative assessment: Comparative analyses of data from field trials located at representative sites and environments in the USA and Europe indicate that maize MON810 is agronomically and phenotypically equivalent to the conventional counterpart and commercially available reference varieties, with the exception of the lepidopteran-protection trait, conferred by the expression of the Cry1Ab protein. The field evaluations support a conclusion of no phenotypic changes indicative of increased plant weed/pest potential of MON810 compared to conventional maize. Evaluations of ecological interactions between maize MON810 and the biotic and abiotic environment indicate no unintended effects of the introduced trait on agronomic and phenotypic characteristics. Environmental risk: There are no reports of the target lepidopteran species attaining pest status on maize in Norway. Since there are no Bt-based insecticides approved for use in Norway, and lepidopteran pests have not been registered in maize, issues related to resistance evolution in target pests are not relevant at present for Norwegian agriculture. Published scientific studies show no or negligible adverse effects of Cry1Ab protein on non-target arthropods that live on or in the vicinity of maize plants. Cultivation of maize MON810 is not considered to represent a threat to the prevalence of red-listed species in Norway. Few studies have been published examining potential effects of Cry1Ab toxin on ecosystems in soil, mineralization, nutrient turnover and soil communities. Some field studies have indicated that root exudates and decaying plant material containing Cry proteins may affect population size and activity of rhizosphere organisms (soil protozoa and microorganisms). Most studies conclude that effects on soil microorganisms and microbial communities are transient and minor compared to effects caused by agronomic and environmental factors. However, data are only available from short term experiments and predictions of potential long term effects are difficult to deduce. Few studies have assessed the impact of Cry proteins on non-target aquatic arthropods and the fate of these proteins in senescent and decaying maize detritus in aquatic environments. However, exposure of non-target organisms to Cry proteins in aquatic ecosystems is likely to be very low, and potential exposure of Bt toxins to non-target organisms in aquatic ecosystems in Norway is considered to be negligible.  Maize is the only representative of the genus Zea in Europe, and there are no cross-compatible wild or weedy relatives outside cultivation with which maize can hybridise and form backcross progeny. Vertical gene transfer in maize therefore depends on cross-pollination with other conventional or organic maize varieties. In addition, unintended admixture of genetically modified material in seeds represents a possible way for gene flow between different crop cultivations. The risk of pollen flow from maize volunteers is negligible under Norwegian growing conditions.  In addition to the data presented by the applicant, the VKM GMO Panel is not aware of any scientific report of increased establishment and spread of maize MON810 and any change in survival (including over-wintering), persistence and invasiveness capacity. Because the general characteristics of maize MON810 are unchanged, insect resistance are not likely to provide a selective advantage outside cultivation in Norway.  Since MON810 has no altered agronomic and phenotypic characteristics, except for the specific target pest resistance, the VKM GMO Panel is of the opinion that the likelihood of unintended environmental effects due to the establishment and survival of maize MON810 will be no different to that of conventional maize varieties in Norway. Overall conclusion: The VKM GMO Panel concludes that cultivation of maize MON810 is unlikely to have any adverse effect on the environment in Norway.

Abstract: In preparation for a legal implementation of EU-regulation 1829/2003, the Norwegian Scientific Committee for Food Safety (VKM) has been requested by the Norwegian Environment Agency (former Norwegian Directorate for Nature Management) and the Norwegian Food Safety Authority (NFSA) to conduct final food/feed and environmental risk assessments for all genetically modified organisms (GMOs) and products containing or consisting of GMOs that are authorized in the European Union under Directive 2001/18/EC or Regulation 1829/2003/EC. The request covers scope(s) relevant to the Gene Technology Act. The request does not cover GMOs that VKM already has conducted its final risk assessments on. However, the Agency and NFSA requests VKM to consider whether updates or other changes to earlier submitted assessments are necessary.  The herbicide-tolerant and insect-resistant genetically modified maize 59122 from Pioneer HiBred/Mycogen Seeds (Unique Identifier DAS-59122-7) is approved under EU Regulation 1829/2003/EC for food and feed uses, import and processing since 24 October 2007 (Application EFSA/GMO/NL/2005/12, Commission Decision 2007/702/EC). An application for granting   consent to all uses of 59122 maize, including cultivation, was submitted by Pioneer in               accordance with articles 5 and 17 of the Regulation (EC) No. 1829/2003 21 October, 2005 (EFSA/GMO/NL/2005/23).   VKM participated in the 90 days public consultation of the application for placing on the market of maize 59122 for food and feed uses, import and processing (EFSA/GMO/NL/2005/12) in 2005, and submitted a preliminary opinion in December 2005 (VKM 2005a). Maize 59122 has also been assessed as food and feed by the VKM GMO Panel, commissioned by the Norwegian Environment Agency and the Norwegian Food Safety Authority in connection with the national finalisation of the application in 2008 (VKM 2008a). Maize 59122 has also been evaluated by the VKM GMO Panel as a component of several stacked GM maize events under Regulation (EC) 1829/2003 (VKM 2007a,b,c, VKM 2008b, VKM 2009, VKM 2012a,b, VKM 2013a,b,c,d). Due to the publication of new scientific literature and updated guidelines for risk assessment of genetically modified plants, the VKM GMO Panel has decided to deliver an updated food/feed and environmental risk assessment of event 59122.  The updated  food/feed and environmental risk assessment of the maize 59122 is based on information provided by the applicant in the applications EFSA/GMO/NL/2005/12 and EFSA/GMO/NL/2005/23 and scientific comments from EFSA and other member states made available on the EFSA website GMO Extranet. The risk assessment also considered other peer-reviewed scientific literature as relevant.    The VKM GMO Panel has evaluated 59122 with reference to its intended uses in the European Economic Area (EEA), and according to the principles described in the Norwegian Food Act, the Norwegian Gene Technology Act and regulations relating to impact assessment pursuant to the Gene Technology Act, Directive 2001/18/EC on the deliberate release into the environment of genetically modified organisms, and Regulation (EC) No 1829/2003 on genetically modified food and feed. The Norwegian Scientific Committee for Food Safety has also decided to take account of the appropriate principles described in the EFSA guidelines for the risk assessment of GM plants and derived food and feed (EFSA 2011a), the environmental risk assessment of GM plants (EFSA 2010a), selection of comparators for the risk assessment of GM plants (EFSA 2011b) and for the post-market environmental monitoring of GM plants (EFSA 2011c).   The scientific risk assessment of maize 59122 include molecular characterisation of the inserted DNA and expression of novel proteins, comparative assessment of agronomic and phenotypic characteristics, nutritional assessments, toxicology and allergenicity, unintended effects on plant fitness, potential for gene transfer, interactions between the GM plant, target and non-target organisms, and effects on biogeochemical processes.   It is emphasised that the VKM mandate does not include assessments of contribution to sustainable development, societal utility and ethical considerations, according to the Norwegian Gene Technology Act and Regulations relating to impact assessment pursuant to the Gene Technology Act. These considerations are therefore not part of the risk assessment provided by the VKM Panel on Genetically Modified Organisms.   Genetically modified maize 59122 expresses the cry34Ab1 and cry35Ab1 genes from Bacillus thuringiensis, conferring resistance to certain coleopteran target pests belonging to the genus Diabrotica, such as the larvae of western corn rootworm (D. virgifera virgifera), northern corn rootworm (D. barberi) and the southern corn rootworm (D. undecimpunctata howardi). None of the target pests for maize 59122 are present in the Norwegian agriculture. Maize 59122 also expresses the phosphinothricin-N-acetyltransferase (pat) gene, from the soil bacterium Streptomyces viridochromogenes. The encoded PAT protein confers tolerance to the herbicidal active substance glufosinate-ammonium. The PAT protein produced by maize 59122 has been used as a selectable marker to facilitate the selection process of transformed plant cells and is not intended for weed management purposes.  Molecular Characterization:  Appropriate analyses of the transgenic DNA insert, its integration site, number of inserts and flanking sequences in the maize genome, have been performed. The results show that only one copy of the insert is present in maize 59122. Homology searches with databases of known toxins and allergens have not indicated any potential production of harmful proteins or polypeptides caused by the genetic modification in maize 59122. Southern blot analyses and segregation studies show that the introduced genes cry34Ab1, cry35Ab1 and pat are stably inherited and expressed over several generations along with the phenotypic characteristics of maize 59122. The VKM GMO Panel considers the molecular characterisation of maize 59122 satisfactory.  Comparative assessment Comparative analyses of maize 59122 to its non-GM conventional counterpart have been performed during multiple field trials in representative areas for maize cultivation in Chile (2002/2003), North America (2003, 2004) and Europe (2003, 2004). With the exception of small intermittent variations, no biologically significant differences were found between maize 59122 and the conventional non-GM control. Based on the assessment of available data, the VKM GMO Panel concludes that maize 59122 is compositionally, agronomical and phenotypically equivalent to its conventional counterpart, except for the introduced characteristics.   Food and Feed Risk Assessment:  A 90-day subchronic feeding study in rats, as well as whole food feeding studies on broilers, laying hens, lactating dairy cows, feedlot steers, and growing-finishing pigs, have not indicated any adverse effects of maize 59122, and shows that maize 59122 is nutritionally equivalent to conventional maize. The PAT, Cry34Ab1 and Cry35Ab1 proteins do not show sequence resemblance to other known toxins or IgE allergens, nor have they been reported to cause IgE-mediated allergic reactions. Some studies have however indicated a potential role of Cry-proteins as adjuvants in allergic reactions.  Based on current knowledge, the VKM GMO Panel concludes that maize 59122 is nutritionally equivalent to conventional maize varieties. It is unlikely that the PAT, Cry34Ab1 and Cry35Ab1 proteins will introduce a toxic or allergenic potential in food or feed based on maize 59122 compared to conventional maize.  Environmental Risk Assessment:  Considering the intended uses of maize 59122, excluding cultivation, the environmental risk assessment is concerned with accidental release into the environment of viable grains during transportation and processing, and indirect exposure, mainly through manure and faeces from animals fed grains from maize 59122.   Maize 59122 has no altered survival, multiplication or dissemination characteristics, and there are no indications of an increased likelihood of spread and establishment of feral maize plants in the case of accidental release into the environment of seeds from maize 59122. Maize is the only representative of the genus Zea in Europe, and there are no cross-compatible wild or weedy relatives outside cultivation. The risk of gene flow from occasional feral GM maize plants to conventional maize varieties is negligible. Considering the intended use as food and feed, interactions with the biotic and abiotic environment are not considered to be an issue.  Overall Conclusion:  Based on current knowledge, the VKM GMO Panel concludes that maize 59122 is nutritionally equivalent to conventional maize varieties. It is unlikely that the PAT, Cry34Ab1 and Cry35Ab1 proteins will introduce a toxic or allergenic potential in food or feed based on maize 59122 compared to conventional maize. The VKM GMO Panel likewise concludes that maize 59122, based on current knowledge, is comparable to conventional maize varieties concerning environmental risk in Norway with the intended usage.