<p>Colorectal cancer is one of the most common malignant diseases in Sweden – more than 5000 new cases are diagnosed each year. The overall five-year survival is about 60% and in cases of recurrence the prognosis is poor.</p><p>In a phase III study in advanced colorectal cancer the response rate was doubled when 5-FU was given as a bolus injection versus as a short infusion. The toxicity was similar and time to progression was longer in the injection group. However, overall survival was not significantly different. Dose-effect relationships of 5-FU were studied in another phase III study recruiting 312 patients. A decrease from 500 mg/m² to 400 mg/m² worsened the treatment results. A low incidence of severe toxicity was seen in both groups. An increase to 600 mg/m² worsened the toxicity without any improvement of the results.</p><p>A cytotoxic drug sensitivity test in different tumour types, mainly gastrointestinal cancer, poorly predicted treatment outcome in a phase II study.</p><p>The conventional Nordic Flv regimen was split in a phase I/II trial. An escalation of dose was possible and the response rate was 20%.</p><p>Thymidylate synthase (TS) and the gene expression of p53 were investigated by immunohistochemical technique in the primary tumours of 132 patients. None of the markers predicted the later palliative chemotherapy result. However, TS significantly predicted time to recurrence.</p><p>Serum markers were analysed before and during FLv treatment to early predict outcomes among 87 patients. TPS is promising, both as a predictive marker before start of treatment and after a short period of treatment. In the same setting, CEA had lower predictive value. S-VEGF and S-bFGF did not yield any prognostic information of later outcome. In all studies B-haemoglobin values, performance status and subjective response were strong markers, both for prediction of objective response and for survival.</p>

Colorectal cancer is one of the most common malignant diseases in Sweden – more than 5000 new cases are diagnosed each year. The overall five-year survival is about 60% and in cases of recurrence the prognosis is poor. In a phase III study in advanced colorectal cancer the response rate was doubled when 5-FU was given as a bolus injection versus as a short infusion. The toxicity was similar and time to progression was longer in the injection group. However, overall survival was not significantly different. Dose-effect relationships of 5-FU were studied in another phase III study recruiting 312 patients. A decrease from 500 mg/m2 to 400 mg/m2 worsened the treatment results. A low incidence of severe toxicity was seen in both groups. An increase to 600 mg/m2 worsened the toxicity without any improvement of the results. A cytotoxic drug sensitivity test in different tumour types, mainly gastrointestinal cancer, poorly predicted treatment outcome in a phase II study. The conventional Nordic Flv regimen was split in a phase I/II trial. An escalation of dose was possible and the response rate was 20%. Thymidylate synthase (TS) and the gene expression of p53 were investigated by immunohistochemical technique in the primary tumours of 132 patients. None of the markers predicted the later palliative chemotherapy result. However, TS significantly predicted time to recurrence. Serum markers were analysed before and during FLv treatment to early predict outcomes among 87 patients. TPS is promising, both as a predictive marker before start of treatment and after a short period of treatment. In the same setting, CEA had lower predictive value. S-VEGF and S-bFGF did not yield any prognostic information of later outcome. In all studies B-haemoglobin values, performance status and subjective response were strong markers, both for prediction of objective response and for survival.

Tesis por compendio / La exposición crónica a sustancias de abuso lleva a cambios adaptativos en el cerebro que implican alteraciones en la expresión génica. Se ha propuesto que los factores de transcripción CREB y deltaFosB serían dianas moleculares para la regulación de la plasticidad, la cual lleva a la adicción.En este trabajo hemos estudiado los cambios en la activación de CREB, en PVN y NTS, y las quinasas que mediarían su activación durante la dependencia y síndrome de abstinencia a morfina, así como la respuesta del eje HHA durante dicho síndrome. También se investigó la posibilidad de que la activación de CREB y su coactivador transcripcional TORC1 dependan de la activación de receptores adrenérgicos. Además se evaluaron las posibles modificaciones en la expresión de FosB/deltaFosB en diferentes áreas cerebrales implicadas en la adicción, así como los cambios neuroendocrinos/neuroquímicos responsables de las alteraciones metabólicas observadas durante el tratamiento crónico con morfina. / Chronic exposure to opioids and other abused drugs results in adaptive changes in the brain involving alterations in gene expression. It is proposed that the transcription factors CREB and deltaFosB be molecular targets for the regulation of plasticity, which leads to addiction.In this work we studied changes in activation of the cAMP-response element binding protein (CREB) in PVN and NTS and the kinases that may mediate this activation during dependence and morphine withdrawal and the HPA axis response after naloxone-induced morphine withdrawal. We also investigated the possibility that the activation of CREB and the transcriptional coactivator of CREB, TORC1, arises from the activation of adrenergic receptors. We also evaluated the possible modifications in FosB/deltaFosB expression in several brain areas involved in addiction and neuroendocrine/neurochemical changes that are responsible for the metabolic alterations seen during chronic morphine treatment.

The stockholm county proposed legislation in 2010 on the use of studded tires in the city. The aim of the policy was to reduce the use of studded tires by 50 percent. The research question investigates the authenticity of the policy where it was hypothesized that the net social benefits for the imposition of this charge was less than or equal to zero. Emperical literatures were chosen systematically and with the help of theories on welfare economics, a meta analysis was employed quantifying cost and benefits of all outcomes. The findings shows that the NSB is less than zero meaning that it was a wise decision to reject the proposal.

In the present study, we have approached the molecular characterization of the HCMV specific UL1. To this end a HCMV (AD169-derived HB5 background) recombinant with an HA-epitope tagged UL1 and a mutant with a full UL1 deletion in the endotheliotropic HCMV TB40/E strain were generated. Our data reveal that the UL1 is transcribed with late kinetics. pUL1 is glycosylated and localizes at the site of virus assembly and secondary envelopment in infected cells forming part of the envelope of HCMV virions. A HCMV mutant with a targeted deletion of UL1 exhibits a growth defect phenotype in retinal pigment epithelium cells but not in fibroblasts, indicating that this ORF encodes a cell-type specific tropism factor. / En aquest treball hem investigat la pauta oberta de lectura de UL1 del Cytomegalovirus humà (HCMV), el gen UL1 es específic del HCMV. Hem caracteritzat la proteïna UL1 modificada amb un epítop HA en la soca HB5, derivada de AD169. L'UL1 s’expressa com una glicoproteïna que es pot detectar a les 48 i 72h post-infecció. En fibroblasts humans infectats, UL1 co-localitza al citoplasma, al lloc d’assemblatge del virió, amb proteïnes estructurals del virus. A més a més, els anàlisis de virions AD169 purificats que contenen UL1-HA mostren que UL1 és un nou constituent de l’envolta del HCMV. La delecció de UL1 en el context de la soca TB40/E del HCMV disminueix el creixement viral de manera selectiva en determinats tipus cel•lulars, suggerint que UL1 podria estar involucrat en la regulació del tropisme cel•lular del HCMV.

This paper tries to answer the question related to the implementation of one of Europe's most influential EU-directives, the Water Framework Directive. The Directive requires Member States to achieve good ecological potential and good surface water chemical status for bodies of water until year 2015. If the states cannot achieve those objectives within this period, then there may be grounds for exemptions from the requirement to prevent further deterioration of to achieve good status under specific conditions. One of those conditions could be that, the completing the improvements within the timescale would be disproportionately expensive. Question which is examined in this paper is, what criteria would be most appropriate for determining the disproportionate costs. Based on the review of most WFD-related studies and EU legislation are selected criteria, which should be used for the assessment of the disproportionate costs.

<p>As the world population continues to grow, it will be challenging to manage resources, reduce environmental pollution and maintain growing demand for food production. Controlled environment agriculture (CEA) is a novel solution to reduce freshwater use in agriculture, minimize environmental pollution from agriculture sector, and meet the growing food demand. CEA allows for the year-round cultivation in inhospitable climatic conditions. Hydroponics is a common method of growing crops in CEA, where plants grow in a solution enriched with nutrients and oxygen. The technique significantly reduces water use and fertilizer run-off during production. In the United States, lettuce is one of the most important crops grown using hydroponics.</p> <p> Hydroponic production uses several methods to grow lettuce including nutrient film technique (NFT) and constant flood table (CFT). Moreover, several cultivars of lettuce are grown in the Midwest. There is a lack of knowledge on whether optimal fertilizer concentrations change depending on the cultivar or hydroponic production system. Little information is known about the suitability of a cultivar to a specific method of hydroponic production. For year-round lettuce production in hydroponics, supplemental lighting (SL) and heating are required in the Midwestern regions of the U.S. The energy requirements for SL and heating can be too costly in winter for some growers to produce crop year-round. In addition to light quantity, spectral composition of light can impact growth. Heating the root zone to produce a micro-climate may be more efficient than heating the entire greenhouse and possibly reduce overall heating costs. However, information on spectral composition of light and the efficacy of root zone heating is unclear, at best. Certain cultivars that can tolerate cold stress can be more suitable in the U.S. Midwest during winter. Lettuce cultivar screening for yield under cooler environments is limited. </p> <p> A completely customizable hydroponic production system that can aid in conducting research related to above-mentioned issues was built as a part of my Master of Science program. Using this system, 24 popular cultivars from four lettuce groups were evaluated for productivity during summer/fall under different concentrations of fertilizer solution, and in two production methods including NFT and CFT during spring. In addition, yield of all 24 cultivars were evaluated under 10, 15.5 and 21.1 °C in a growth chamber. The eight best performing cultivars from the summer/fall trial were evaluated during the winter in a greenhouse with the addition of SL and root zone heating with minimal ambient air heating. </p> <p> Results indicated that the lowest level of electrical conductivity (EC) of the fertilizer solution used (1.3 dS·m^-1) resulted in highest yield, regardless of cultivar or method of production. Among the 24 cultivars; Red Sails (Leaf), Salvius (Romaine), Cedar (Oakleaf), and Adriana (Butterhead) had the highest yields among each group during summer. Growth chamber study indicated that Dragoon, Adriana, New Fire Red and Red Sails cultivars had higher yields than other cultivars under cooler (10 and 15.5 °C) air temperature conditions. In the winter study, lettuce cultivars did not reach harvestable size even after 40 days of growth without SL and root zone heating. Supplemental light composition significantly affected lettuce growth with higher yield under Purple (with higher proportion of red) than White LED lighting. Commercially acceptable lettuce could be produced using root zone heating. In general, plants grown under CFT yielded higher than those grown under NFT in the winter trial. Among the cultivars, Salvius, Black Seeded Simpson, Cedar, and Red Sails performed better under SL and root zone heating during winter.</p>

<p>This thesis aims to evaluate a Modular Manufacturing (MM) technical approach to Controlled Environment Agriculture (CEA) for cultivating plant food crops in a repurposed urban space. The specific approach was to fit a modular hydroponic CEA system into an insulated cooler box with environmental control to act as a micro plant factory. The feasibility of the approach was evaluated and a benchmark comparison between repurposed urban space and controlled lab environments was produced.</p><p>Possessing accessibility and affordability to desired quantitatively and nutritious food is a pillar for a healthy lifestyle, yet food insecurity is a growing problem worldwide, in industrial as well as industrializing nations. Food insecurity is defined as “lacking the ability to meet nutritional needs at one or multiple times during the year.” [1] Though Developing countries tend to score poorly on the Food Security Index [2], the issue is common in developed countries as well, where countries like the U.S. Possess a household food insecurity rate of above 10% [1]. Especially, subgroups of the urban population and university students in developed countries are represented at a higher rate concerning food insecurity [3], due to food insecurity’s dependence on socioeconomic factors such as purchasing power and local accessibility.</p><p>Bringing production close to the consumers or to the Point-of-Need (PoN) would be a valuable tool for supplementing traditional food crop production and increasing access to high-quality food for groups exposed to food insecurity. This is especially attractive in densely populated areas and college campuses, where real estate is prime. Bringing production to the PoN does however carry certain challenges, such as severe resource restrictions, which are not present in traditional agricultural production in rural areas where there is vast access to land, water, and plenty of sunlight. Pushing the boundaries of CEA research, technology, and application areas will be crucial for the utilization of nontraditional agricultural land, agricultural resource optimization, and food security improvements in difficult-to-farm environments to facilitate delivery to PoN.</p><p><br></p><p><b>Salient outcomes:</b> The salient outcomes of this research were that a MM platform was proven to be feasible for CEA cultivation of food crops in a repurposed urban space as well as a controlled location. Specimens cultivated in a repurposed urban space were shown to have a lower growth rate compared to a controlled location, but the important comparison is to the currently nonexistent productivity in such spaces.</p><p><b>Intellectual merit:</b> The MM CEA platform was designed, prototyped, and tested using components-of-the-shelf (COTS) as recommended by frugal engineering methodology [4]. This manufacturing platform was engineered for a case study for repurposing unused “garage space” on the college campus at Purdue University. The platform was further used for a set of studies to evaluate the feasibility of the MM platform and the production efficiency of the platform not only in a repurposed urban space but also across harsh environments across winter-spring seasons. Romaine lettuce cultivars were used as a sample plant for winter and spring studies due to their property as a popular consumable, nutritious, and relatively short growth time for better productivity. The following research issues were addressed by this research: (1) design of a modular manufacturing module; (2) testing of the module in the indoor controlled lab environment; (3) advancing design based on findings in no.2; (4) CEA testing of the integration of multiple modules (two and water supply) in the Purdue University garage (living lab) and the indoor lab environment.</p><p><b>Broader Impact:</b> The results from this research could serve as a proof-of-concept to validate the feasibility of functional modules and their integration in scaled-up urban food crop production using repurposed space. This case study especially could open opportunities for college campuses across the US (and the world), to repurpose multi-storied garage spaces for healthy food production at PoN, for example, accessible to students’ dorms and cafeterias. This MM model could further be extended to other forms of urban areas for food security and production in communities in the vicinity of garages and similar spaces in form. Utilizing unrecognized space resources in an otherwise resource-restricted environment could be the supplemental production needed to fight food desertification and insecurity in urban locations. Bringing food production to the PoN would increase the accessibility of high-quality and nutritious fresh produce, improving conditions for localized food insecurity problems.</p>

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<p dir="ltr">Controlled environment agriculture (CEA) is a practice of food production under optimized conditions to intensify production yield, and thus has potential for addressing food security for a growing population. Aquaculture and aquaponics are two types of CEA that can produce aquatic animals along with plants using non-arable lands and lower inputs of water and nutrients. However, their operations have high energy consumption and generate considerable nutrient-rich sludge and wastewater, making their environmental performance an emerging research focus. This thesis quantitively analyzed the environmental sustainability of aquaponics and aquaculture production using life cycle assessment (LCA).</p><p dir="ltr">The LCA on aquaponics evaluated a marine aquaponics production system that grew shrimp, red orache, minutina and okahajiki, and analyzed the effect of salinity, C/N ratio, and shrimp-to-plant stocking density. The grow-out stage accounted for over 90% of total environmental impacts with electricity use as the predominant contributor. The marine aquaponic production exhibited best environmental performance when operated at low salinity (10 ppt), and high C/N ratio (15) and stocking density (5:1), which can be further improved by 95–99% via the use of wind power as electricity source. Additionally, variation in the prices of aquaponic products was found to improve the system’s environmental impacts by up to 8%.</p><p dir="ltr">The aquaculture LCA focused on shrimp recirculating aquaculture systems (RAS) and evaluated the environmental feasibility of microalgae-based wastewater treatment. Microalgae treatment effectively removed 74% of phosphate in RAS wastewater and thus reduced the freshwater eutrophication potential by 55%. However, its remediation performance was inferior to activated sludge treatment due to different operation scales. Electricity was the principal hotspot of microalgae treatment and made up over 99% of all the environmental impacts, which can be considerably decreased by reducing coal use in the electricity supply. Three utilization pathways for algal biomass (feed ingredient, biodiesel and biogas) were investigated; however, only biogas production was found to show environmental benefits to marine eutrophication remediation owing to the low biomass quantity produced.</p><p dir="ltr">While <a href="" target="_blank">aquaculture and aquaponics</a> play important roles in meeting the globally growing demand for seafood, this thesis provides valuable life cycle inventory data for these fields. Moreover, the LCA models developed in this thesis are useful decision-making tools for aquaculture and aquaponic producers to adapt farming practices with lower environmental footprint.</p>