This thesis has been conducted in collaboration with JM AB, Region Öst, based at their office in Uppsala. Below follows a summary of the study. Problem For the major contractors in Sweden, the costs after the costumers access are high. According to Boverket the costs can be as high as 1.3 billion SEK annually. In addition of the costs of the work itself, the companies risks dissatisfied customers when the extra work often is considered as a disturbance. To investigate this matter, the purpose of this thesis is to answer the following questions: - What are the most common errors reported during the warranty period? - Can the errors be addressed at an earlier stage? - Is poor purchasing a contributing factor to the high costs during the warranty period? - Can a different ventilation system reduce the amount of errors? Method The purpose of the study is to identify the most common errors that occur during the warranty period, to summarize these and give concrete suggestions of measures to reduce the errors. The report is based on interviews, statistics of the errors from JM Region Öst during year 2015 and the analysis of the customers feedback during the warranty period of eight projects. In addition, the authors have chosen to compare two different ventilations systems to see if the change of system can reduce the number of error reports concerning ventilation. Conclusions The study shows an even distribution of errors from the different categories. The reports from JM Region Öst during year 2015 and the average from the selected projects have similar distribution. Of the total number of error reports from JM Region Öst during year 2015, 20.1 percent belonged to the category Plumbing. The same category had, in the authors compilation of the eight projects, 20.2 percent of the reports. From this result it can be concluded that the percentage of problems reported from each category is about the same, no matter the size of the project. In the interviews, the most common errors and what causes these, were discussed. Because of the many errors to the category Plumbing, this was the main subject. During the interviews it was discovered that different actors blames the problems on each other. However, dirt in the pipe system in combination with a low water pressure was considered to be the biggest cause of problems to the category. The study also shows that a complicated list of responsibilities generates costs for the after-sales department. The reason is that the process of appointing a responsible actor becomes hard. The consequence of this is that staff from the after-sales department is forced to make visits to the projects only to be able to redirect the matter to the responsible subcontractor.

Endometriosis is a gynecological disease defined as the growth of endometrium outside of the uterus. Although linked to 50% of female infertility cases, current medical treatments fail to maintain fecundity. Since the survival of endometriotic lesions is dependent on their early neovascularization, antiangiogenic therapies specifically targeting blood vessel growth could be a promising therapeutic option for the treatment of endometriosis. Angiogenesis, the branching of new blood vessels from existing vasculature, promotes robust vascularization of lesions. ABT-898 (Abbott Laboratories), a thrombospondin-1 analog, induces endothelial cell apoptosis while sequestering pro-angiogenic growth factors. We postulated that ABT-898 would reduce endometriotic lesion vascularization while physiological angiogenesis and pregnancy remained unaffected in a murine model of endometriosis. The antiangiogenic effect of ABT-898 was tested in a human umbilical vein endothelial cell line revealing disruption of endothelial tube branching. Two in vivo experiments were conducted in which endometriosis was induced in female alymphoid BALB/c-Rag2-/-Il2rg-/- mice by adhering sections of human endometrium to the abdominal wall. Lesions from ABT-898 treated mice contained a reduced number of CD31+ endothelial cells and a decrease in blood flow supplying the lesion compared to 5% dextrose controls. Reproductive status was evaluated through maintenance of pregnancies up to gestation day 12 revealing unaffected implantation site structure and physiological angiogenesis. In a trans-generational study, pregnant F0 generation mice received ABT-898 or 5% dextrose injections on gestation days 7, 9, 11, 13, 15, 17, and 19. F1 generation mice were raised to reproductive age and bred resulting in litters (F2 generation) comparable in size to the F0 generation litters. Chronic exposure to ABT-898 did not affect angiogenic plasma cytokine levels in F0 generation mice. In addition, physiological angiogenesis was unaffected within the uteri of ABT-898 treated mice. Histological examination of the kidney, liver, ovary, and uterus revealed no structural abnormalities in F0 and F1 generations exposed to ABT-898. These results suggest that ABT-898 inhibits pathological angiogenesis within endometriotic lesions without affecting physiological angiogenesis involved in pregnancy and organ function across three generations of mice. Further research will establish the effects of ABT-898 on embryonic development, organ toxicity, and physiological angiogenesis in all organs. / Thesis (Master, Anatomy & Cell Biology) -- Queen's University, 2013-05-07 15:19:10.967

Head and neck cancer is the sixth leading cancer worldwide. Head and neck squamous cell carcinoma (HNSCC) accounts for more than 90% of incident cases. Despite intense, multimodality treatment regimens for HNSCC including surgery, chemotherapy, and radiation, little progress has been made over the past 30 years in improving overall survival rates. Tumor cell death induced by both conventional and targeted chemotherapy is often mediated by the BCL-2 family-dependent mitochondrial apoptotic pathway. However, initiators of this apoptotic pathway, such as p53, are more than 50% of the time mutated or deleted in HNSCC rendering the disease refractory to treatment. To counter such resistance, direct therapeutic targeting of the BCL-2 family is conceptually appealing. For this purpose, we use three clinically-available drugs: cisplatin, fenretinide, and ABT-263 (navitoclax). Both cisplatin and fenretinide are known to induce a BH3-only pro-apoptotic protein, Noxa, which binds to and inactivates multi-domain anti-apoptotic protein MCL-1 and release from its interaction with multi-domain pro-apoptotic protein BAK, followed by the phosphorylation via CDK2 for the proteasome-mediated degradation. Activated BAK can now go through conformational change for the oligomerization at the outer membrane of the mitochondria to release cytochrome c into the cytosol and induce caspase-dependent apoptotic cell death. ABT-263 directly binds to multi-domain anti-apoptotic proteins, such as BCL-2 and BCL-XL, to inhibit their activity and leads to the activation of multi-domain pro-apoptotic protein BAX to induce apoptosis. We hypothesize that combining the Noxa-inducing drugs (cisplatin or fenretinide) along with ABT-263 can efficiently induce BAX and BAK activation and significantly increase cell death in HNSCC cells by simultaneously inhibiting the activity of MCL-1, BCL-2, and BCL-XL. Combination-induced treatments in four cell lines (HN8, HN30, HN31, and UMSCC1) tested led to significant increase in apoptotic cell death. Cisplatin and ABT-263 combined treatment is inducing the expression of Noxa and leading to increase in apoptosis in HN30, HN31, UMSCC1, but not HN8. Similarly, fenretinide and ABT-263 combined treatment is inducing the expression of Noxa in all four cell lines tested and is largely relying on expression of Noxa.

Head and neck cancer accounts for approximately 3 percent of all cancers in the United States, and over 90% of them are head and neck squamous cell carcinoma (HNSCC). Chemotherapeutic drugs that treat HNSCC can activate BCL-2 family dependent apoptosis. Pro-apoptotic NOXA induced by adenovirus (Ad-NOXA) or fenretinide inactivates anti-apoptotic MCL-1, while ABT-263 can inactivate other anti-apoptotic BCL-2 family members such as BCL-2 and BCL-XL. We used p53 inactive HN8 and HN12, p53 wild-type UMSCC1, and HPV-positive UMSCC47 human HNSCC cell lines and five mouse HNSCC cell lines. Cells were treated with Ad-NOXA, ABT-263, and fenretinide alone or in combinations. Combinational treatment of ABT-263 with Ad-NOXA or fenretinide enhanced cell death among all cell lines we tested regardless of p53 status. These findings support the hypothesis that combinational treatment of Ad-NOXA or fenretinide with ABT-263 increases cell death by simultaneously inhibiting all anti-apoptotic BCL-2 family proteins in HNSCC cells.

Since their inception in the early 1960s, Australian content requirements for commercial television have been subjected to considerable scrutiny through a series of formal inquiries. Over the last ten years this process has intensified. In recent years there have been a number of academic criticisms regarding the state of debate about the regulation of Australian content on commercial television and the capacity of the debate to generate genuine criticism and embrace change. This thesis examines the dynamics of debate about Australian content. It focuses on the ABT's Inquiry into Australian Content on Commercial Television (ACI) which ran from 1983 to 1989. It takes as its basic point of reference Jurgen Habermas' concept of the 'public sphere'. This concept refers to a realm of social life, separate from the state and private spheres, in which 'public opinion' can be formed. Habermas has argued that, with the refeudalisation of the public sphere, the state and private interests have increasingly collaborated to close off the public sphere. The thesis concludes that in many respects Habermas' concept of a refeudalised 'public sphere' is a useful explanatory tool for understanding the dynamics of the ACI and the limited degree of criticism generated by it. However, Habermas' model is limited in so far as it fails to accord adequate recognition to the complexities and significance of the mediation of the 'public interest' by key participants in the inquiry and the strategic role of rhetoric for these participants. Habermas concludes that with the refeudalisation of the public sphere and the disappearance of the historical conditions which supported its operation, the public sphere must now be reconstructed on a case by case basis. Attempts to achieve this, have tended to focus on the facilitation of citizen participation in public policy debate. However, as this analysis of the ACI demonstrates, the dynamics of the debate itself appear to limit I the degree to which 'public opinion' can be elevated above 'private interest'. This thesis demonstrates that the mediation of the 'public interest' assumed a central role in the rhetoric and strategy of the ACI. Each of the key players represented distinct interests and were largely unaccountable to the 'public' they claimed to serve. This thesis concludes that in order to gain a more detailed understanding of how communication works in such a context, and in order to conceive of alternative participatory forms, we need to focus on those aspects of public discourse which Habermas neglects: the rhetoric and the strategic nature of public representation. It suggests that fruitful avenues for further study may lie with Bantz's notion of communicative structures or Luhmann's systems approach to communication.

La progression tumorale est la conséquence de multiples altérations génotypiques et phénotypiques; L’une d’entre elles, nécessaire à la formation de métastases, est l’acquisition d’une résistance à l’anoïkis, forme d’apoptose induite par la perte d’attachement à la matrice extra-cellulaire. Afin d’étudier l’anoïkis, nous avons utilisé deux lignées colorectales humaines isogéniques : la lignée SW480 dérivée de la tumeur primaire et sensible à l’anoïkis et la lignée SW620 dérivée d’une métastase ganglionnaire de cette même tumeur et résistante à l’anoïkis. Nous avons établi que dans les cellules SW480, l’anoïkis est une forme d’apoptose intrinsèque c'est-à-dire débutant à la mitochondrie et donc sous le contrôle des protéines de la famille Bcl-2. Parmi celles-ci, nous avons trouvé que seule la protéine proapoptotique à BH3-seul Bim était régulée différemment dans les deux lignées : tandis que son expression augmente de manière très significative dans les cellules SW480 cultivées en suspension, elle n’augmente que très peu dans les cellules SW620. De manière très intéressante, et malgré cette différence, les deux lignées se sont montrées être sensibles au BH3-mimétique ABT-737 mais seulement lorsqu’elles sont cultivées en suspension. Ces résultats indiquent que, qu’elles soient sensibles ou non à l’anoïkis, les cellules détachées sont « prédisposées à la mort » et que des composés semblables à l’ABT-737 tels que le Navitoclax ou l’ABT-199 pourraient avoir des propriétés anti-métastiques dans les tumeurs solides. Dans la seconde partie de ce travail, nous montrons que la protéine transmembranaire CDCP1 ( CUB Domain Containing Protein 1) semble nécessaire mais non suffisante pour protéger ces cellules contre l’anoïkis. CDCP1 est un substrat de Src mais sa phosphorylation sur tyrosine n’est pas impliquée dans cette protection. Finalement, nous avons identifié deux nouvelles protéines qui interagissent avec CDCP1 : l’ITGB4 et l’EphA2 / Tumour progression is the consequence of multiple genotypic and phenotypic alterations. One of these, necessary for the formation of metastasis, is acquisition of a resistance to anoïkis, a form of apoptosis triggered by loss of attachment to the extra-cellular matrix. In order to study anoïkis, we used two isogenic human colon cell lines : SW480 cells derived from the primary tumour and sensitive to anoïkis, and SW620 cells derived from a lymph node metastasis in the same patient which are resistant to anoikis. We found that anoikis signaling in SW480 cells is a form of intrinsic apoptosis thus starting at the mitochondria and under the control of Bcl-2 family proteins. Among the members of this family, the BH3-only proapoptotic protein Bim was the only one that we found to be differentially regulated between the two cell lines: whereas Bim expression augments strongly during the culture in suspension of SW480, it only slightly does so in SW620 cells. Most interestingly, despite this difference, both cell lines turned to be sensisitive to the BH3-mimetic ABT-737 but only when they are in suspension. This shows that, whether or not they a sensitive to anoikis, detached colon cancer cells are “primed for death” and thus that ABT-737 related compounds such as Navitoclax or ABT-199 might have anti-metastatic properties in solid tumours. In the second part of this work, we show that the transmembrane protein CDCP1 (CUB Domain Containing Protein 1) appears be necessary but not sufficient to protect these cells against anoïkis. CDCP1 is a Src substrate but its tyrosine phosphorylation is not involved in this protection. Finally, we have identified two new proteins interacting with CDCP1: ITGB4 and EphA2.

No description available.

Inom byggindustrin genomförs besiktningar för att säkerställa att en entreprenad har levereratden beställda slutprodukten enligt de krav som beställaren angivit angående kvalitet ochfunktion. För att säkerhetsställa att besiktningsanmärkningar undviks i entreprenaden syftar denhär studien till att söka hjälpmedel som kan användas för att uppnå en förbättradbesiktningsprocess inom byggindustrin. För att undersöka hur och var en förbättring är möjligatt genomföra har en kartläggning över besiktningsanmärkningar utförts. Kartläggningenkompletterades med intervjuer för att få yrkesverksamma personer hos Skanska att ge sin synpå hur Skanska kan förbättra sin besiktningsprocess. Skanska har nyligen infört en nybesiktningsrutin i slutskedet av byggprocessen i syfte att minska antalet anmärkningar och fånöjdare kunder.I studien har effekten av den nya besiktningsrutinen undersökts och resultatet visar att de är pågod väg att nå sina mål men att det fortfarande finns förbättringspotential. Med den nya rutinenupptäcks anmärkningarna i ett tidigare skede än vad som gjordes tidigare, vilket skapar tid föratt avhjälpa dem innan slutbesiktningen. Det medför att anmärkningarna bli färre påslutbesiktningen även om det totala antalet fel fördelat över hela besiktningsprocessenfortfarande är detsamma.Resultatet från både kartläggningen och intervjuerna gav tydliga indikationer på var fokus börläggas för att uppnå en förbättrad besiktningsprocess. De bidragande faktorerna till det visaderesultatet diskuteras och förslag på förbättringsåtgärder presenteras.Förhoppningsvis kan rapporten bidra med en förståelse för hur besiktningsprocessen ibyggindustrin går till samt vilka de största felkällorna till att entreprenader får mångabesiktningsanmärkningar är och hur dessa skulle kunna undvikas. / Within the construction industry, inspections of the construction are made to secure that thequality and its functions are accurate according to the demands from the purchaser of theproject. This study examines different tools that can be helpful to use in order to secure a lowrange of inspection remarks to achieve an improved inspection process within the constructionindustry. To investigate how and where an improvement can be made, a survey of inspectionremarks were performed. The survey was supplemented by an interview to gain employersaspect on how Skanska could achieve an improved inspection process. Skanska has recentlyintroduced a new routine of the inspections, with the purpose of reducing the number of remarksand getting satisfied customer.The effect of the new routine has been studied and the result shows that Skanska is not far fromreaching the goal, however improvements can still be made. The new routine provides a betteropportunity to locate the remarks earlier in the construction process and there for more time torepair the remarks is gained. Thus there will be fewer remarks on the final inspection eventhough the overall numbers of remarks during the whole inspection process will remain thesame.Both the survey and interview manifested the areas where focus should be directed in order toimprove the inspection process. The contributing factors to the results are discussed andproposals for improvements are presented.This study will hopefully contribute to an understanding for the inspection process within theconstruction industry. Also bring understanding for the reasons why construction often gets alarge number of inspection remarks and how they could be avoided.

Baskartan innehåller högdetaljerad geografisk information som ligger till grund för olika verksamhets-delar i en kommun. Ajourhållning av baskartan innebär en noggrann och krävande process för att säkerställa dess innehåll. Kvalitetskraven på innehållet varierar utifrån syfte och ändamål samt styrs av olika standarder och riktlinjer. Ett avtal som kommunerna tillsammans med Lantmäteriet kan ingå är, Ajourhållningen av adress- och byggnadsinformation samt information om övrig topografi (ABT-avtal). Avtalet innehåller dataspecifikationer som beskriver bl.a. riktlinjer kring insamling av specifika geodata, dataformat och datakvalitet. I avtalet ingår att leverans av kvalitetssäkrade byggnadsgeometrier ska ske. Avtalets syfte är att kommunerna tillsammans med Lantmäteriet uppnår en hållbar och kvalitativ process kring geografiska data. Syftet med studien var att utveckla, testa och utvärdera en metod i Topocad för att kvalitetssäkra byggnadsgeometrier med avseende på logisk konsistens, enligt ramen för ABT-avtal. Detta för att skapa ett underlag som kan användas för arbetsrutiner vid handhavande av byggnadsgeometrier. Studieområde är Hagfors, en mindre tätort i norra Värmland.  I studien presenteras en specifik metod för kvalitetsprocessen i programvaran Topocad med stöd av den kvalitetskontroll som utförs av Lantmäteriets i programvaran FME. Kvalitetsprocessen omfattar kontroll av logisk konsistens och skapande av byggnadsytor. Målet med arbetet är att testa och utvärdera Topocads kapacitet att klassificera och korrigera topologiska fel i polylinjer samt skapande av polygoner. Därför i arbetet har klassificering och korrigering testats och utvärderats för ett urval av felaktiga byggnadsgeometrier genom inbyggda funktioner i Topocad. Därtill har även skapande av polygoner utförts genom en automatiserad funktion utifrån de korrigerade byggnadsgeometrierna. I resultatet framgår att klassificeringen av topologiska fel i Topocad är till viss del icke tillförlitlig. Detta eftersom en specifik typ av polylinjer med lösa noder inte kan klassificeras. Därtill framgår även att det är möjligt att korrigera och kvalitetssäkra de övriga polylinjerna med lösa noder som Topocad klarar att klassificera med hjälp av lämpliga toleransparametrar. Dessutom visar resultatet att det är genomförbart att skapa polygoner av de klassificerade och korrigerade polylinjerna. Samtidigt är polygonernas tillförligtighet och kvalitet helt beroende av de tillämpade toleransparametrarna samt de uppställda kvalitetskraven.     Slutsatsen är att det inte är möjligt att utveckla en metod för hela kvalitetsprocessen som kvalitetssäkrar byggnadsgeometrier i Topocad enligt ABT-avtalet. Detta eftersom vissa delar av kvalitetsprocessen är otillförlitliga eller ej genomförbara. / The basemap contains highly detailed geographical information that is the foundation for several functions in the municipalities in Sweden. The upkeep of the basemap involves a specific and ever-evolving process to ensure the quality of its content. The quality requirements for the basemap content vary according to the purpose and are moderated by different standards and guidelines. The Maintenance of Address and Building Information and Information of Other Topography, ABT-agreement (ABT-avtal). This voluntary agreement presents guidelines and encloses data specifications on the gathering of specific geodata, data formats, and the logical consistency of the delivery. One specific part of the agreement includes the delivery of quality-assured building geometries. The agreement offers municipalities and The Department of Land Surveying (Lantmäteriet) in Sweden to enter collectively to construct a sustainable and qualitative process around the geographical information. The purpose of this study was, therefore, to develop and evaluate a quality process for the quality assurance of the building geometries regarding their logical consistency, according to the ABT agreement. This quality process can lead to creating a foundation for correctly handling the building geometries. Therefore, The Department of Land Surveying has contributed with its own quality control process to help the municipalities achieve a higher data quality. The quality control process was created in Feature Manipulation Engine (FME) program. The study area was a small urban area in the town Hagfors, situated in the north eastern part of the county of Värmland, Sweden. The study presents a specific method for the quality process in the software Topocad with the support of The Department of Land Surveying own quality control process. The method content is divided into two different parts that manage with the logical consistency in the polylines and the creation of polygons from the building geometries. The method was to test and evaluate Topocads capacity to classify and correct topological errors in the polylines, but also the creation of polygons. Classification and correction were performed for a selection of incorrect building geometries through program-built functions. In addition, the creation of polygons was also performed for the corrected building geometries through an automated function in Topocad. The result shows that the classification of topological errors in Topocad is, to a certain degree, unreliable. This because Topocad cannot classify a specific type of polylines with loose nodes. Furthermore, it also appears that it is possible to correct the other polylines with loose nodes that Topocad can manage to classify and thereby assure their quality. Moreover, the result shows that it is achievable to create polygons of the classified and corrected polylines in Topocad. At the same time, the reliability of the polygons is entirely dependent on the cluster tolerance applied in the method and the quality requirements established for the results. The study concludes that it is not possible to develop a method for the whole quality process that assure the quality of the building geometries in Topocad, according to the ABT-agreement. This because some parts of the quality process are unreliable or unachievable.

Byggavtalet AB 04 återfinns inom entreprenadrättens område, ett område vars särdrag bland annat utgörs av bristen på lagregleringar. Istället bildar avtalen i den så kallade AB-familjen en systematik som fungerar såsom reglering som används och accepteras av de flesta parter på området. Ryggraden, och stommen, i denna systematik utgörs av avtalet AB 04 för generalentreprenader och delade entreprenader, och ABT 06 för totalentreprenader. De övriga avtalen (bland andra AB-U 07, ABT-U 07, ABM 07 och ABK 09) innehåller liknande typer av regler och är utformade för att fungera tillsammans i en kontraktskedja. Under entreprenadarbeten används som regel byggavtalet AB 04 mellan såväl byggherre och entreprenör, som entreprenör och dennes underentreprenörer. Ansvarsfördelningen för en skada på tredje man regleras genom 5:13 i AB 04, och skada på sådana som inte är tredje man i 5:11. Definitionen av vem som utgör tredje man och vem som inte gör det är således central för förståelsen av ansvarsfördelningen mellan beställare och entreprenör. 5:11 och 5:13 skiljer sig åt vad gäller ansvarsform (presumtionsansvar i 5:13, och culpaansvar eller felansvar i 5:11) och placeringen av bevisbördan. Dessutom innehåller 5:11 ansvarsbegränsningar vad gäller beloppet (15 % av kontraktssumman, eller det belopp som ansvarsförsäkring utgör) och industriell produktion eller annan kommersiell verksamhet. Genom den vida skrivningen i 5:13 och genom att ingen praxis finns i frågan finns osäkerhet kring frågan om ansvarsfördelningen. Med tredje man i den betydelse som åsyftas i 5:13 måste, enligt uppsatsens resultat, förstås alla som inte är part i avtalet, undantaget underentreprenörer, underleverantörer och övriga som står i avtalsförhållande med någon av parterna avseende entreprenaden. Det vill säga såväl sådana skadelidande som är helt frikopplade från avtalsparterna, som skadelidande som står i avtalsförhållande med någon av parterna, men inte rörande entreprenaden. Med detta som grund blir effekten att de skadetyper som räknas in under första stycket i 5:13 är alla skador som kan träffa dessa personer som kan vara tredje man. Det finns inget gehör för begränsningar av vad paragrafen är ”åsyftad” att innebära, likt de Byggandets kontraktskommitté (BKK) ger uttryck för i sina yttranden. En osäkerhet av den typ som finns i AB 04 är olämplig, med tanke på de stora skillnader som finns i 5:11 och 5:13. Genom ett förtydligande av paragraf 5:13 vid exempelvis nästa revidering av AB 04, och en anpassad standardiserad försäkringslösning, skulle problematiken enkelt kunna undvikas.