Sammanfattning Examensarbete i företagsekonomi, Ekonomihögskolan vid Linnéuniversitetet i Växjö, logistikavdelningen, 4FE05E, VT2012. Författare: Philip Troedsson och Tobias Gill Handledare: Petra Andersson Examinator: Helena Forslund Titel: Kartläggning, kostnadsberäkningar och förbättringsåtgärder för kundorderprocessen för beställningsartiklar - En fallstudie på Fredells VVS-, El- & Kakelavdelning. Bakgrund: Fredells Logistikchef Cabevi, (2012) har uppmärksammat att kundorderprocessen för Fredells beställningsartiklar på VVS-, El- & Kakelavdelningen skulle behöva studeras med avseende på att beräkna kostnaderna och undersöka om processen kan effektiviseras. Syfte: Syftet med studien är att utifrån en ABC-kalkyl beräkna kostnaderna och vinsten för ett urval av fem beställningsartiklar på Fredells VVS-, El- & Kakelavdelning. Dessutom är syftet att genom en processkartläggning kartlägga kundorderprocessen för beställningsartiklar och vilka för personalen kända problem som förekommer i processen. Syftet är även att identifiera förbättringsåtgärder för dessa problem. Metod: I denna fallstudie har ett positivistiskt synsätt med en deduktiv forskningsansats tillämpats. För att samla in data har intervjuer genomförts med kvalitativ metod. Respondenterna har bestått av Fredells personal på flera olika avdelningar och den empiriska datainsamlingen har huvudsakligen baserats på intern kommunikation med företaget. Slutsats: De problemfrågor som besvaras i studien berör ämnena processkartläggning, ABC-kalkylering och processförbättring. Enligt analysen har sex aktiviteter kunnat detekteras i kundorderprocessen för beställningsartiklar på VVS-, El- & Kakelavdelningen och problem har upptäckts i fyra av dessa. Kostnaderna för de fem utvalda beställningsartiklarna har visat sig variera, dock inte i någon större utsträckning. Vinsten har å andra sidan varierat mer, där två artiklar har visat sig vara olönsamma. Flera förbättringsåtgärder har identifierats, vilka skulle kunna leda till att kundorderprocessen för beställningsartiklar effektiviserades.

Cancer remains the most cause death disease in Taiwan at least ten years. Liver cancer, which consists predominantly of hepatocellular carcinoma (HCC), is the most common cause of cancer mortality in men and the second most in women. Not only liver section and liver transplantation are used in HCC therapy but also local ablation therapy and transarterial therapy. Transarterial chemoembolization (TACE) is one of the local therapies that inject chemotherapeutic drugs directly into liver tumor. However, drug resistance is the mainly restriction in patient after chemotherapy. Moreover, it is known that drug resistance was associated to over-expression of certain ABC transporter genes, especially ABCB1, ABCG2, and ABCC family in cancer cell and those ABC transporters were also expressed in liver. Base on clinical study, they use 5-fluororuacil, cisplatin and mitomycin-C for liver cancer treatment. In this study, we hypothesized that cancer therapies may be augmented through blocked the drug efflux ABC channels with the ABC transporter inhibitors such as verapamil. The associations among drug treatments, inhibitor incorporation and the expression of ABC transporters were evaluated in HepG2 and Hep3B cells. MTT assay demonstrated that the cell viability was considerable decreased by treating triple drugs with verapamil. RT-PCR data showed that ABC transporters mRNA expression has no significantly change. However, membrane ABCB1 and ABCG2 were induced after drugs and inhibitors treatment either 1 or 24 hours by flow cytometry analysis. P-glycoprotein functional assay also showed p-glycoprotein was inhibited by verapamil, and hence Rhodamine 123 retention was increased. Taken together, there are different response of ABC transporters in HepG2 and Hep3B after drugs and inhibitors treatment. Membrane ABCB1 and ABCG2 were induced by drugs and inhibitors treatment. However, p-glycoprotein¡¦s function was restrained simultaneously by inhibitors treatment. Therefore, verapamil can enhance cell death by inhibiting ABC transporters and its cytotoxic effect rather than the increased expression of ABC transporters. This finding might provide a better way in liver cancer therapy.

Det här examensarbetet har genomförts för Runsven och har haft som syfte att studera de effekter som kan uppstå i butik om leveransfrekvensen från lager till butik ökar. Runsven AB är tillsammans med ÖoB helägda dotterbolag till Runsvengruppen AB, där Runsven svarar för varuförsörjning och logistik medan ÖoB svarar för marknadsarbete och försäljning. I dagsläget får ÖoB-butikerna två ordinarie leveranser i veckan från Runsvens centrallager. Runsven tror att en ökad leveransfrekvens kan ge positiva effekter i form av ett minskat butikslager samtidigt som fyllnadsgraden, det vill säga andelen tillgängliga produkter i butiken, ökar. Man tror också att förändringen kan ge förbättringar för butikspersonalen. Syftet i arbetet uppfylls genom en studie av tre olika frågeställningar: Hur påverkas butikslagret? Hur påverkas orderkvantiteterna? Hur påverkas personalen? Metoden i arbetet, som har använts för att besvara frågeställningarna, har varit en konstruktion av en modell som studerar lagerstorlek och lagerföringskostnader samt tidsåtgång för arbete i samband med leveranser. Baserat på modellens resultat utfördes sedan Activity-based costing-kalkyl (ABC-kalkyl), som visar olika produkters kostnad för de aktiviteter som krävs i samband med leverans. Arbetets resultat visar att butikerna idag har för mycket produkter i lager. Modellens resultat visar att en ökad leveransfrekvens kan ge en minskning av en butiks lagerföringskostnader med mellan 21 och 49 procent, beroende på hur leveransfrekvensen ökas. Rapportens resultat visar också att en ökad leveransfrekvens skulle ge förbättringar för butikspersonalen. Slutligen visar ABC-kalkylen att den aktivitet som förbrukar flest resurser och därmed kostar mest är aktiviteten upplockning. För aktiviteten mottagning är däremot kostnaderna genomgående låga, på grund av detta har mindre fokus lagts på denna aktivitet.

The main theme in this thesis is the ABC conjecture. We prove some partial results towards it and we find new applications of this conjecture, mainly in the context of B\"uchi's n squares problem (which has consequences in logic related to Hilbert's tenth problem) and squarefree values of polynomials. We also study related topics, such as arithmetic properties of additive subgroups of Hecke algebras, function field and meromorphic value distribution, and undecidability of the positive existential theories over languages of arithmetic interest. / Thesis (Ph.D, Mathematics & Statistics) -- Queen's University, 2014-04-28 10:47:54.064

The aim of this project was to study ATP binding cassette (ABC) transporters in the human placenta, in particular their regulation and role in trophoblast differentiation and survival. The presence and localisation of four major placental drug transporters, multidrug resistance gene product 1 and 3 (MDR1 and 3)/ABC subfamily B members 1 and 4 (ABCB1 and 4), multidrug resistance associated proteins 1 and 2 (MRP1 and 2)/ABCC1 and 2 and breast cancer resistance protein (BCRP)/ABCG2 was initially studied in term human placenta, cultured primary trophoblast and BeWo and Jar trophoblast-like cell lines. Jar cells were found to be more similar to nondifferentiated cytotrophoblast with respect to their ABC protein expression profile, whereas BeWo cells more closely reflected differentiated syncytiotrophoblast. Treatment of primary term trophoblasts in vitro with cytokines (TNF- or IL-1) decreased expression and activity of apical transporters ABCB1/MDR1 and ABCG2/BCRP. Growth factors, on the other hand, increased BCRP expression and activity, while estradiol stimulated BCRP, MDR1 and MDR3 expression MDR1/3 functional activity. The ability of BCRP/ABCG2 to abrogate the apoptotic effects of TNF- and ceramides was studied in primary trophoblast and BeWo cells using pharmacological and molecular (siRNA) approaches. The results suggest that BCRP/ABCG2 contributes to the resistance of trophoblast cells to cytokine-induced (extrinsic) apoptosis, whereas its effects on apoptosis activated via the intrinsic mitochondrial pathway is minimal. This altered resistance was associated with increased intracellular accumulation of ceramides and reduced ability to maintain phosphatidylserine in the inner leaflet of the plasma membrane. A role for BCRP/ABCG2 in cell protection from differentiation-induced stressors was also demonstrated during the process of cell fusion associated with transient loss of plasma membrane lipid asymmetry. Finally, expression of BCRP/ABCG2 (and 9 other genes) was studied in 50 placentas from normal pregnancy and pregnancies complicated with fetal growth restriction (FGR). A marked reduction of BCRP/ABCG2 and MDR1/ABCB1 expression was observed in FGR placentas, while other transporter genes were unaffected. Collectively these data suggest that BCRP/ABCG2 and probably other ABC transporters may play a hitherto unrecognised survival role in the placenta, conferring a “stress resistance” to trophoblast cells.

The aim of this project was to study ATP binding cassette (ABC) transporters in the human placenta, in particular their regulation and role in trophoblast differentiation and survival. The presence and localisation of four major placental drug transporters, multidrug resistance gene product 1 and 3 (MDR1 and 3)/ABC subfamily B members 1 and 4 (ABCB1 and 4), multidrug resistance associated proteins 1 and 2 (MRP1 and 2)/ABCC1 and 2 and breast cancer resistance protein (BCRP)/ABCG2 was initially studied in term human placenta, cultured primary trophoblast and BeWo and Jar trophoblast-like cell lines. Jar cells were found to be more similar to nondifferentiated cytotrophoblast with respect to their ABC protein expression profile, whereas BeWo cells more closely reflected differentiated syncytiotrophoblast. Treatment of primary term trophoblasts in vitro with cytokines (TNF- or IL-1) decreased expression and activity of apical transporters ABCB1/MDR1 and ABCG2/BCRP. Growth factors, on the other hand, increased BCRP expression and activity, while estradiol stimulated BCRP, MDR1 and MDR3 expression MDR1/3 functional activity. The ability of BCRP/ABCG2 to abrogate the apoptotic effects of TNF- and ceramides was studied in primary trophoblast and BeWo cells using pharmacological and molecular (siRNA) approaches. The results suggest that BCRP/ABCG2 contributes to the resistance of trophoblast cells to cytokine-induced (extrinsic) apoptosis, whereas its effects on apoptosis activated via the intrinsic mitochondrial pathway is minimal. This altered resistance was associated with increased intracellular accumulation of ceramides and reduced ability to maintain phosphatidylserine in the inner leaflet of the plasma membrane. A role for BCRP/ABCG2 in cell protection from differentiation-induced stressors was also demonstrated during the process of cell fusion associated with transient loss of plasma membrane lipid asymmetry. Finally, expression of BCRP/ABCG2 (and 9 other genes) was studied in 50 placentas from normal pregnancy and pregnancies complicated with fetal growth restriction (FGR). A marked reduction of BCRP/ABCG2 and MDR1/ABCB1 expression was observed in FGR placentas, while other transporter genes were unaffected. Collectively these data suggest that BCRP/ABCG2 and probably other ABC transporters may play a hitherto unrecognised survival role in the placenta, conferring a “stress resistance” to trophoblast cells.

The aim of this project was to study ATP binding cassette (ABC) transporters in the human placenta, in particular their regulation and role in trophoblast differentiation and survival. The presence and localisation of four major placental drug transporters, multidrug resistance gene product 1 and 3 (MDR1 and 3)/ABC subfamily B members 1 and 4 (ABCB1 and 4), multidrug resistance associated proteins 1 and 2 (MRP1 and 2)/ABCC1 and 2 and breast cancer resistance protein (BCRP)/ABCG2 was initially studied in term human placenta, cultured primary trophoblast and BeWo and Jar trophoblast-like cell lines. Jar cells were found to be more similar to nondifferentiated cytotrophoblast with respect to their ABC protein expression profile, whereas BeWo cells more closely reflected differentiated syncytiotrophoblast. Treatment of primary term trophoblasts in vitro with cytokines (TNF- or IL-1) decreased expression and activity of apical transporters ABCB1/MDR1 and ABCG2/BCRP. Growth factors, on the other hand, increased BCRP expression and activity, while estradiol stimulated BCRP, MDR1 and MDR3 expression MDR1/3 functional activity. The ability of BCRP/ABCG2 to abrogate the apoptotic effects of TNF- and ceramides was studied in primary trophoblast and BeWo cells using pharmacological and molecular (siRNA) approaches. The results suggest that BCRP/ABCG2 contributes to the resistance of trophoblast cells to cytokine-induced (extrinsic) apoptosis, whereas its effects on apoptosis activated via the intrinsic mitochondrial pathway is minimal. This altered resistance was associated with increased intracellular accumulation of ceramides and reduced ability to maintain phosphatidylserine in the inner leaflet of the plasma membrane. A role for BCRP/ABCG2 in cell protection from differentiation-induced stressors was also demonstrated during the process of cell fusion associated with transient loss of plasma membrane lipid asymmetry. Finally, expression of BCRP/ABCG2 (and 9 other genes) was studied in 50 placentas from normal pregnancy and pregnancies complicated with fetal growth restriction (FGR). A marked reduction of BCRP/ABCG2 and MDR1/ABCB1 expression was observed in FGR placentas, while other transporter genes were unaffected. Collectively these data suggest that BCRP/ABCG2 and probably other ABC transporters may play a hitherto unrecognised survival role in the placenta, conferring a “stress resistance” to trophoblast cells.

The aim of this project was to study ATP binding cassette (ABC) transporters in the human placenta, in particular their regulation and role in trophoblast differentiation and survival. The presence and localisation of four major placental drug transporters, multidrug resistance gene product 1 and 3 (MDR1 and 3)/ABC subfamily B members 1 and 4 (ABCB1 and 4), multidrug resistance associated proteins 1 and 2 (MRP1 and 2)/ABCC1 and 2 and breast cancer resistance protein (BCRP)/ABCG2 was initially studied in term human placenta, cultured primary trophoblast and BeWo and Jar trophoblast-like cell lines. Jar cells were found to be more similar to nondifferentiated cytotrophoblast with respect to their ABC protein expression profile, whereas BeWo cells more closely reflected differentiated syncytiotrophoblast. Treatment of primary term trophoblasts in vitro with cytokines (TNF- or IL-1) decreased expression and activity of apical transporters ABCB1/MDR1 and ABCG2/BCRP. Growth factors, on the other hand, increased BCRP expression and activity, while estradiol stimulated BCRP, MDR1 and MDR3 expression MDR1/3 functional activity. The ability of BCRP/ABCG2 to abrogate the apoptotic effects of TNF- and ceramides was studied in primary trophoblast and BeWo cells using pharmacological and molecular (siRNA) approaches. The results suggest that BCRP/ABCG2 contributes to the resistance of trophoblast cells to cytokine-induced (extrinsic) apoptosis, whereas its effects on apoptosis activated via the intrinsic mitochondrial pathway is minimal. This altered resistance was associated with increased intracellular accumulation of ceramides and reduced ability to maintain phosphatidylserine in the inner leaflet of the plasma membrane. A role for BCRP/ABCG2 in cell protection from differentiation-induced stressors was also demonstrated during the process of cell fusion associated with transient loss of plasma membrane lipid asymmetry. Finally, expression of BCRP/ABCG2 (and 9 other genes) was studied in 50 placentas from normal pregnancy and pregnancies complicated with fetal growth restriction (FGR). A marked reduction of BCRP/ABCG2 and MDR1/ABCB1 expression was observed in FGR placentas, while other transporter genes were unaffected. Collectively these data suggest that BCRP/ABCG2 and probably other ABC transporters may play a hitherto unrecognised survival role in the placenta, conferring a “stress resistance” to trophoblast cells.

Proefschrift Universiteit van Amsterdam. / Met bibliogr., lit. opg.

University, Diss., 2006--Frankfurt (Main). / Zsfassung in engl. und dt. Sprache.