Withdrawing from the Istanbul Convention: de jure and de facto consequences

The thesis concerns the opportunity to withdraw from the Istanbul Convention, and the legal and factual consequences withdrawal entails.MasteroppgaveJUS399MAJUR-2MAJU

Characterization of bioactive natural products from edible, medicinal and toxic plants

Research performed during work on this thesis has focused on isolation, structure elucidation and biological activity of natural products. Seven plant species have been examined, namely Bromelia laciniosa Mart. ex Schult f., Encholirium spectabile Martius ex Schult. Schult. f., Metasequoia glyptostroboides Hu & Cheng, Narthecium ossifragum L. Huds., Neoglaziovia variegata Arruda da Camara Mez, Viscum album L. and Zamioculcas zamiifolia Lodd. Engl. Fifty-five compounds are reported throughout the thesis. Among them are twelve novel natural products. Artemia toxicity test, 1,1-diphenyl-2- picrylhydrazyl (DPPH) scavenging activity and 15-lipoxygenase inhibition test have been performed on pure compounds and in one case on crude extracts. Four novel natural products and four known compounds are reported from European white-berry mistletoe (V. album L.). Two novel aminoalkaloids 4,5,4’- trihydroxy-3,3’-iminodibenzoic acid and 4,5,4’,5’-tetrahydroxy-3,3’- iminodibenzoic acid were isolated and identified from the leaves of V. album. This is the first time alkaloids that appear to be specific to this medicinal plant used for millennia are reported in the scientific literature. The two novel natural products 3-(3’-carbomethoxypropyl) gallic acid and 3-(3’-carbomethoxypropyl)- 7→3’’-protocatechoyl galloate make up a novel group of natural products. They are derived of the methyl ester of γ-hydroxybutyric acid (GHB) coupled to aromatic hydroxybenzoic acids including gallic acid. Radical scavenging activity for 3-(3’-carbomethoxypropyl) gallic acid (IC50 value 222 μM) were twentyfold reduced by substitution of the 3-hydroxyl of gallic acid with the methyl ester of gamma-hydroxybutyric acid compared with that of gallic acid ((IC50 value 27.7 μM). From dawn redwood (M. glyptostroboides) altogether eight compounds are reported including the novel natural product 6-carboxydihydroresveratrol 3-O-β- glucopyranoside. This dihydrostilbenoid exhibited both radical scavenging activity (IC50 value 164±39μM) and inhibition of 15-Lipoxygenase (IC50 value 246±30μM). Apigenin-6-C-(6’’-O-(3-hydroxy-3-methylglutaroyl)-β-glucopyranoside, a novel acylated C-glycosylflavone, and six other known natural products are reported from Z. zamiifolia. This ancient African medicinal plant has recently seen widespread use as an indoor ornamental plant. Z. zamiifolia has gained a reputation for being toxic. Despite this no lethality was observed even at the highest concentrations (1 mg/ml) when crude extracts of both leaves and petioles were applied in initial toxicological tests with Artemia salina. From the three species of the Bromeliaceae family, B. laciniosa (nine compounds), N. variegata (thirteen compounds) and E. spectabile (sixteen compounds), a total of twenty non-polar natural products are reported. Prior to this investigation very little information was available about the chemical composition of these three Bromeliaceae spp. Very long chain alkanes, fatty acids, tocopherols and triterpenoids are among the reported compounds. Twelve aromatic compounds are reported from the fruits of bog asphodel (N. ossifragum). Six novel natural products namely, (E)-4-(3-R-hydroxy-2,2- dimethylChroman-6-yl)but-3-en-3-one, (E)-4-(4-(((E)-4-hydroxy-3-methylbut- 2-en-1-yl)oxy)Phenyl)but-3-en-2-one, (2R,3S)-Naringenin(3→6’’)luteolin, (2R,3S)-Naringenin(3→6’’)chrysoeriol, liovil 4-O-β-glucopyranoside and (E)- 2,6-dimethoxycinnamic acid were reported for the first time. Previous to this investigation the rare natural product 4-hydroxy-3-(3-methylbut-2-enyl) benzaldehyde was only known from the pathogenic fungus Heterobasidion occidentale. This fungal metabolite was shown to be cytotoxic towards both normal rat kidney (NRK) (IC50 value 430 μM) and MOLM13 acute myeloid leukemia (AML) cells (IC50 value 68 μM). Naringenin(3→6’’)luteolin was the main aromatic compound, and was shown to be toxic to A. salina (LC50 value 130μM). This novel biflavonoid was cytotoxic for both NRK (IC50 value 230 μM) and MOLM13AML cells (IC50 value 115 μM).Forskningen utført i løpet av denne doktorgraden har fokusert på isolering, strukturoppklaring og biologisk aktivitet til naturprodukter. De syv planteartene Bromelia laciniosa Mart ex. Schult. f., Encholirium spectabile Martius ex Schult. Schult. f., Metasequoia glyptostroboides Hu & Cheng, Narthecium ossifragum (L.) Huds., Neoglaziovia variegata (Arruda da Camara) Mez, Viscum album L. and Zamioculcas zamiifolia (Lodd.) Engl har blitt undersøkt. Femtifem naturprodukter er rapportert i denne avhandlingen deriblant tolv hittil ukjente forbindelser. Rene forbindelser og i ett tilfelle et råekstrakt har blitt testet med Artemia toksistets test, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radikal sluk effekt og 15-lipoxygenase inhiberingstest. Fire nye og fire kjente forbindelser er rapportert fra europeisk hvitbæret misteltein (V. album L.). De to aminoalkaloidene 4,5,4’-trihydroksy-3,3’- iminodibenzosyre og 4,5,4’, 5’-tetraydroksy-3,3’-iminodibenzosyre er isolert og identifisert for første gang fra bladene til V. album. For første gang er det i den vitenskaplige litteraturen rapportert alkaloider som ser ut til å være spesifikke for denne medisinplanten som har vært brukt i årtusener. To nye naturstoffer basert på metyl esteren av gammahydroksysmørsyre (GHB) forbundet med aromatiske hydroksybenzosyrer inkludert gallussyre (3,4,5- trihydroksybenzosyre) er nå rapportert. De to nye forbindelsene 3-(3’- karbometoksypropyl) gallussyre og 3-(3’-karbometoksypropyl)- 7→3’’protocatechoyl galloat utgjør en ny gruppe av naturprodukter. Radikalslukeffekten av 3-(3’-carbometoksypropyl) gallussyre (IC50 verdi 222 μM) var redusert med en faktor på tjue i forhold til gallussyre uten substituering (IC50 verdi 27,7 μM). Totalt åtte forbindelser er rapportert fra urtreet M. glyptostroboides inkludert det nye naturproduktet 6-karboksydihydroresveratrol 3-O-β-glukopyranosid. Det ble påvist både radikal sluk effekt (IC50 verdi 164±39 μM) og inhibering av 15- lipoksygenase (IC50 verdi 246±30 μM) for denne nye dihydrostilbenoid forbindelsen. Apigenin-6-C-(6’’-O-(3-hydroksy-3-metylglutaroyl)-β-glukopyranosid, en ny acylert C-glykosylflavon, og seks andre naturprodukter er rapportert fra Z. zamiifolia. I det siste har denne gamle afrikanske medisinplanten fått ustrakt brukt som innendørs dekorasjonsplante. Z. zamiifolia har gjennom assosiasjon med andre planter i Araceae familien fått et rykte for å være giftig. Toksisitets test med Artemia salina viste imidlertid ingen dødelighet selv for de høyeste konsentrasjonene (1 mg/ml) for råekstrakt fra blader og stengel fra Z. zamiifolia. Totalt tjue upolare naturstoffer er rapportert fra de tre Bromeliaceae artene B. laciniosa (ni forbindelser), N. variegata (tretten forbindelser) og E. spectabile (seksten forbindelser). Svært lite informasjon var tilgjengelig om den kjemiske sammensetningen til disse tre artene før denne studien ble gjennomført. Fettsyrer, tokoferoler, svært langkjedede alkaner og triterpenoider er blant de rapporterte forbindelsene. Tolv aromatiske forbindelser er rapportert fra frukten til Rome (N. ossifragum) deriblant de seks nye naturproduktene (E)-4-(3-R-hydroksy-2,2-dimetylkroman- 6-yl)but-3-en-3-on, (E)-4-(4-(((E)-4-hydroksy-3-metylbut-2-en-1- yl)oksy)fenyl)but-3-en-2-on, (2R,3S)-Naringenin(3→6’’)luteolin, (2R,3S)- Naringenin(3→6’’)chrysoeriol, liovil 4-O-β-glukopyranosid og (E)-2,6- dimetoksykanelsyre. Før denne studien var det sjeldne naturproduktet 4- hydroksy-3-(3-metylbut-2-enyl) benzaldehyd kun kjent fra den patogene soppen Heterobasidion occidentale. Denne soppmetabolitten ble vist å være cytotoksisk for både normal rat kidney (NRK) (IC50 verdi 430 μM) og MOLM13 acute myeloid leukemia (AML) celler (IC50 verdi 68 μM). Naringenin(3→6’’)luteolin var den aromatiske hovedforbindelsen i fruktene av N. ossifragum og viste seg å være toksisk for A. salina (LC50 verdi 130 μM). Denne nye biflavonoiden var cytotoksisk for både NRK (IC50 verdi 230 μM) og MOLM13 AML (IC50 verdi 115 μM) celler

Exploring Multiway Dataflow Constraint Systems for programming Robotic Autonomous Systems

Denne avhandlingen utforsker programmering av robot-systemer ved hjelp av en programmeringsmodell som heter Multiway Dataflow Constraint Systems.Masteroppgave i informatikkINF399MAMN-INFMAMN-PRO

Parcel Delivery with Automated Parcel Lockers in Bergen: A Study on Potential Collaboration in the Parcel Delivery Industry in Bergen Using Mixed-Integer Linear Programming

Automated parcel lockers (APLs) have in the past year become a common sight in Bergen and have quickly become one of the preferred methods for picking up parcels in the business-to-customer market. As the largest postal companies keep increasing their number of APLs, and an increasing number of companies are implementing or exploring the possibilities to implement APLs in their operations, new problems and solutions arise. This thesis focuses on postal companies’ incentives to partake in collaborative efforts regarding APLs by sharing APLs, terminals, or both. We use mixed-integer linear programming to create different network design models to minimize the cost of delivering parcels with APLs for different scenarios. We then assess and compare the incentives to collaborate in the different scenarios by looking at the relative savings for each scenario. The main findings show that the total cost decreases as collaboration and consolidation increase. We found that when companies share APLs and terminals, collaboration results in significantly higher savings when the cost of APLs is low relative to travel cost. However, we did not find that this was the case when companies only share APLs. In scenarios with several smaller companies, there is a higher incentive to collaborate, as collaboration can be valuable for smaller companies as they are less likely to use the full capacity of APLs when operating individually. This was the case when companies shared only APLs and when sharing both APLs and terminals. The further away the terminals are from each other, the larger the benefit of collaboration becomes when sharing terminals and APLs, but not when only sharing APLs. However, the total cost becomes higher when the terminals are placed further away from the city centre. Lastly, we found that it is possible to find several stable cost allocations when the companies share both terminals and APLs.nhhma

Localization of Crowdfunding Platforms : The Influencing Role of Culture, Institutions and Geography

Master's thesis Business Administration BE501 - University of Agder 2019This master thesis examines the role played by culture, geography and institutions onEuropean crowdfunding platform’s decision to localize their content towards international markets. The authors conducted a binary logistic regression analysis is based on 470 observations of platform-country dyads collected from 269 European crowdfunding platforms and supplemented by additional sources of macro level indicators. Of the eleven hypotheses, social trust, geographical distance, high-context culture, rule of law and the investment orientation on platform have an effect on the decision to localize the platforms. IT infrastructure and the cultural dimensions of individualism, uncertainty avoidance, as well as a compounded variable of cultural distance, did not impact the same decision. The study’s findings are limited contextually to European crowdfunding platforms offering lending, equity, donation and reward-based models. Other micro-factors or countries of operation may exhibit different patterns than what is presented in this thesis. The study is one of the first in the field of localization andcrowdfunding, opening up for new discussions and insights. The results constitute and challenge the pre-existing theory on website localization. This thesis’ findings suggest that the context of this research is of significant impact as cultural adaptation has been highlighted to be one of the key factors to succeed in foreign markets in other industries

Targeted Metabolomic and Transcriptomic Analyses of “Red Russian” Kale (Brassicae napus var. pabularia) Following Methyl Jasmonate Treatment and Larval Infestation by the Cabbage Looper (Trichoplusia ni Hübner)

Methyl jasmonate (MeJA), synthesized in the jasmonic acid (JA) pathway, has been found to upregulate glucosinolate (GS) biosynthesis in plant species of the Brassicaceae family. Exogenous application of MeJA has shown to increase tissue GS concentrations and the formation of myrosinase-mediated GS hydrolysis products (GSHPs). In vitro and in vivo assays have demonstrated the potential health-promoting effects of certain GSHPs. MeJA is also known to elicit and induce genes associated with defense mechanisms to insect herbivory in Brassica species. To investigate the relationship between MeJA-induced GS biosynthesis and insect defense, three treatments were applied to “Red Russian” kale (Brassicae napus var. pabularia) seedlings: (1) a 250 μM MeJA leaf spray treatment; (2) leaf infestation with larvae of the cabbage looper (Trichoplusia ni (Hübner)); (3) control treatment (neither larval infestation nor MeJA application). Samples of leaf tissue from the three treatments were then assayed for changes in GS and GSHP concentrations, GS gene biosynthesis expression, and myrosinase activity. Major differences were observed between the three treatments in the levels of GS accumulation and GS gene expression. The insect-damaged samples showed significantly lower aliphatic GS accumulation, while both MeJA and T. ni infestation treatments induced greater accumulation of indolyl GS. The gene expression levels of CYP81F4,MYB34, and MYB122 were significantly upregulated in samples treated with MeJA and insects compared to the control group, which explained the increased indolyl GS concentration. The results suggest that the metabolic changes promoted by MeJA application and the insect herbivory response share common mechanisms of induction. This work provides potentially useful information for kale pest control and nutritional quality

Transcriptome and Metabolome Analyses of Glucosinolates in Two Broccoli Cultivars Following Jasmonate Treatment for the Induction of Glucosinolate Defense to Trichoplusia ni (Hübner)

Lepidopteran larvae growth is influenced by host plant glucosinolate (GS) concentrations, which are, in turn, influenced by the phytohormone jasmonate (JA). In order to elucidate insect resistance biomarkers to lepidopteran pests, transcriptome and metabolome analyses following JA treatments were conducted with two broccoli cultivars, Green Magic and VI-158, which have differentially induced indole GSs, neoglucobrassicin and glucobrassicin, respectively. To test these two inducible GSs on growth of cabbage looper (Trichoplusia ni), eight neonate cabbage looper larvae were placed onto each of three plants per JA treatments (0, 100, 200, 400 M) three days after treatment. After five days of feeding, weight of larvae and their survival rate was found to decrease with increasing JA concentrations in both broccoli cultivars. JA-inducible GSs were measured by high performance liquid chromatography. Neoglucobrassicin in Green Magic and glucobrassicin in VI-158 leaves were increased in a dose-dependent manner. One or both of these glucosinolates and/or their hydrolysis products showed significant inverse correlations with larval weight and survival (five days after treatment) while being positively correlated with the number of days to pupation. This implies that these two JA-inducible glucosinolates can influence the growth and survival of cabbage looper larvae. Transcriptome profiling supported the observed changes in glucosinolate and their hydrolysis product concentrations following JA treatments. Several genes related to GS metabolism differentiate the two broccoli cultivars in their pattern of transcriptional response to JA treatments. Indicative of the corresponding change in indole GS concentrations, transcripts of the transcription factor MYB122, core structure biosynthesis genes (CYP79B2, UGT74B1, SUR1, SOT16, SOT17, and SOT18), an indole glucosinolate side chain modification gene (IGMT1), and several glucosinolate hydrolysis genes (TGG1, TGG2, and ESM1) were significantly increased in Green Magic (statistically significant in most cases at 400 M) while UGT74B1 and MYB122 were significantly increased in VI-158. Therefore, these metabolite and transcript biomarker results indicate that transcriptome profiling can identify genes associated with the formation of two different indole GS and their hydrolysis products. Therefore, these metabolite and transcript biomarkers could be useful in an effective marker-assisted breeding strategy for resistance to generalist lepidopteran pests in broccoli and potentially other Brassica vegetables

Novel GHB-derived natural products from European mistletoe (Viscum album)

Context: The European white-berry mistletoe [Viscum album L. (Loranthaceae)] is among the oldest known medicinal plants. At present the most important application of mistletoe extracts is in the treatment of cancer. However, natural products specific to mistletoe have rarely been encountered in the current literature. Objective: To discover novel natural products specific to European mistletoe. Materials and methods: European mistletoe was extracted with methanol, purified to partition against diethyl ether and further purified with XAD-7 column chromatography. Pure compounds were separated by Sephadex column chromatography and preparative HPLC. The structures of the novel compounds were established using a combination of several 2D NMR spectroscopic techniques and mass spectrometry. Results: A new type of natural product derived from the methyl ester of g-hydroxybutyric acid (GHB) coupled to hydroxybenzoic acids, namely 3-(3'-carbomethoxypropyl) gallic acid and 3-(3'-carbomethoxypropyl)-7→3''-protocatechoyl galloate were characterized from European white-berry mistletoe. Condensation of the 3-hydroxyl of gallic acid with the 4-hydroxyl of GHB significantly reduced the radical scavenging properties of the former compound. Discussion and conclusion: The characterized compounds define a novel group of natural products that may be of particular interest because it appears that the two new compounds are not closely related to any known natural product.acceptedVersio