<p>Today, wireless communications is used more then ever before. Wired systems are replaced with wireless versions. New methods and transmission standards are developed and tested. The purpose of this thesis is development of a flexible high-performance System Test Platformfor test of the SoCTRix Wireless LAN Transceiver. </p><p>The result is a Xilinx Virtex-II FPGA based System Test Platform board with CardBus PC Card interface to a computer. The hardware achieved has the following features:</p><p>- 8-layer PCB</p><p>- PCMCIA CardBus PC Card interface, enabling 133 MB/s data throughput</p><p>- 1M Gate Virtex-II FPGA with reprogrammable configuration memory</p><p>- Debugging via LEDs and Logic Analyzer connectors</p><p>- 2x SPI EEPROM</p><p>- 40 MHz system clock</p><p>- Easy connection of two daughter-boards</p><p>Specially designed for wireless transmitter development, can also be used for other computer related highperformance applications.</p>

<p>The report descripbs how a diplexer for a hybrid analog/digital filterbank has been constructed and tested. A diplexer divides the frequency band into two different bands that do not who doesn't overlapp each other. The sampling rate for the two ADC:s is 80 Msps, and therefore it is advantage to have zero at 80 MHz. The reason for this is that a proposed class of hybrid filterbanks with very good quality requires a zero at or close the sampling frequency to work well. </p><p>The diplexer was made in three versions. The first didn't work since the choosen inductance self resonance frequency was to low and by the same range as the filters bandwidth. The second version had to much losses, which resulted in attenuation at 80 MHz, which was to small. The third version was made in two differents layout. </p><p>To the diplexer it was also made a test tool in Labview, through that one gets the magnitude ande phase functions. </p><p>The results show that the magnitude function is good for version 3.0 and for version 3.1, and that the losses are low. It depends also on that the choosen components have a high self resonance frequency. There can't been shown any differences between these two, thus is is difficult to judge if one is better then an other.</p>

<p>Persistent environmental pollutants were examined for their interaction with the glucocorticoid hormone system. The focus was placed on interference with the glucocorticoid synthesis and the glucocorticoid-signalling pathway in various <i>in vitro</i> test systems.</p><p>Several aryl methyl sulphones competitively inhibited CYP11B1 activity in mouse adrenocortical Y1 cells. The DDT metabolite, 3-methylsulphonyl-2,2’-bis(4-chlorophenyl)-1,1’-dichloroethene (3-MeSO₂-DDE) had a higher affinity to the enzyme than the endogenous substrate, 11-deoxycorticosterone. In fact, 3-MeSO₂-DDE (K_i 1.6 μM) was almost as potent as the drug metyrapone (K_i 0.8 μM), a well-known inhibitor of the enzyme. 3-MeSO₂-DDE inhibited CYP11B1 activity in human adrenocortical H295R carcinoma cells, and at higher concentrations the CYP21 activity. The human H295R cell line seems to be a useful test system for studies of enzyme activities and could be used to screen endocrine disrupting chemicals interfering with the glucocorticoid hormone synthesis.</p><p>Several chiral PCB methyl sulphones and the fungicide tolylfluanid proved to be antagonists to the glucocorticoid receptor (GR) in rat hepatoma cells and/or Chinese hamster ovary cells stable transformed with a human GR and a responsive reporter vector. The 4-methylsulphonyl-2,3,6,2’,4’,5’-hexachlorobiphenyl (4-MeSO₂-CB149) enantiomers had similar antagonistic effect on the GR. Co-exposure of substances led to additive inhibitory effects on glucocorticoid-regulated protein synthesis in rat hepatoma cells. In general, 4-substituted but not 3-substituted methylsulphonyl-PCBs interacted with the glucocorticoid hormone system.</p><p>In the environment, humans and wildlife are constantly exposed to a wide range of chemicals. Considering the effects of these substances via mechanisms of actions described in this thesis, interference of xenobiotics with the glucocorticoid hormone system deserves further attention. In conclusion, environmental pollutants can interact with the glucocorticoid hormone system <i>in vitro</i>, yet the effects of the tested substances on this hormone system remain to be established <i>in vivo.</i></p>

<p>A gill filament-based assay for the cytochrome P450 1A (CYP1A)-catalysed activity ethoxyresorufin <i>O</i>-deethylase (EROD) was developed in rainbow trout (<i>Oncorhynchus mykiss</i>) and applied to Atlantic salmon (<i>Salmo salar</i>), Arctic charr (<i>Salvelinus alpinus</i>), Atlantic cod (<i>Gadus morhua</i>), saithe (<i>Pollachius virens</i>), and spotted wolffish (<i>Anarhichas minor</i>). Exposure to waterborne β-naphthoflavone (βNF; 10^-6 M) induced branchial EROD activity in all species but the spotted wolffish. In rainbow trout exposed to low concentrations of benzo[a]pyrene (BaP; 10^-9 M) and the textile dye indigo (10^-8 M) the gills responded more rapidly than the liver to BaP, and indigo induced branchial but not hepatic EROD activity.</p><p>A CYP1A-dependent BaP adduct formation was shown in gills of fish exposed to waterborne ³H-BaP, i.e. the adduct formation was enhanced by βNF and blocked by ellipticine (CYP1A inhibitor). The predominant location for BaP adducts was the secondary lamellae (most exposed part of the gill filament), whereas the CYP1A enzyme was also present in the primary lamellae of the gill filament. Hence, in addition to the cell-specific expression of CYP1A an important determinant for the localisation of adducts seemed to be the bioavailability of BaP. This idea is supported by the fact that the CYP1A enzyme was induced only in secondary lamellae by BaP (10^-7 M) and indigo (10^-6 M), whereas it was induced in both primary and secondary lamellae by 3,3´,4,4´,5-pentachlorobiphenyl (10^-8 M). Apparently, readily metabolised inducers (BaP and indigo) are biotransformed in the secondary lamellae.</p><p>My results show that gill filament EROD activity is a sensitive biomarker of exposure to waterborne dioxin-like pollutants, and that the assay has potential for use in monitoring. Furthermore, the results suggest that readily metabolised dioxin-like compounds absorbed via the gills may undergo first-pass metabolism in the gill cells and therefore remain undetected by monitoring of EROD activity in the liver.</p>

Les milieux aquatiques constituent des réservoirs ultimes pour de nombreux polluants organiques persistants,notamment les polychlorobiphényles (PCB, composés bioaccumulables) et les hydrocarbures aromatiques polycycliques (HAP, composés accumulés dans le sédiment et métabolisés par les vertébrés). Les poissons peuvent être exposés à ces polluants à plusieurs stades de vie, ce qui peut altérer leur intégrité fonctionnelle. Les objectifs de cette thèse étaient d'évaluer les altérations physiologiques entrainées par des expositions représentatives de situations environnementales. Ainsi, d'une part, des juvéniles et adultes de poissons zèbres ont été exposés par voie trophique à des mélanges de PCB représentatifs des estuaires européens. Les résultats montrent que la bioaccumulation varie en fonction des congénères de même que le transfert vers les oeufs, et pour ce dernier, le niveau de substitution par des chlores est déterminant. Une altération de la reproduction caractérisée par une réduction du taux de fécondation et l'apparition d'une atrésie folliculaire massive ont été montrées. Ces travaux pourraient être complétés 1) au niveau moléculaire pour mieux comprendre les mécanismes sous-jacents et notamment l'activité perturbateur endocrinien et 2) par l'évaluation des effets au niveau des populations par une approche de modélisation. D'autre part, des embryons ont été exposés pendant 96h à des sédiments enrobés par des HAP individuels. Les phénotypes obtenus sont conformes aux effets décrits pour ces HAP et ont permis de valider la procédure d'exposition. Cette procédure pourrait être utilisée pour évaluer la toxicité de sédiments naturels après extraction de la fraction aromatique, ainsi que pour évaluer la toxicité de molécules hydrophobes. Pour être fiable dans le cadre de tests, il reste indispensable d'identifier des marqueurs précoces d'effets tardifs pour éviter de sous-estimer la toxicité d'un composé.

Humans are continuously exposed to complex mixtures of anthropogenic chemicals. This thesis focus on human exposure to persistent organic pollutants (POPs). POPs ability to bioaccumulate and biomagnify together with the extensive historical use of POPs in e.g. agriculture and industry have resulted in detection of these compounds in humans and animals from all over the world. Adverse health effects caused by POPs are of particular concern for newborns and young individuals. The objective of this thesis is to assess human exposure to a selected set of POPs and their metabolites. More specifically, one aim of my thesis is to determine the exposure to polychlorinated biphenyls (PCBs) and in particular their methylsulfonyl and hydroxylated metabolites in humans from a “hot-spot” area of PCB contamination in eastern Slovakia. The maternal transfer of these chemicals is studied. Further, another specific aim is to determine occurrence, levels and, when possible, temporal trends of POPs in children and adults from three developing countries, Nicaragua, Guinea-Bissau and Bangladesh. High concentrations of PCBs and their metabolites are shown in men and women from Michalovce in eastern Slovakia. Placental transfer of methylsulfonyl-metabolites of PCBs and 4,4’-DDE was observed for the first time. Decreasing temporal trends of the majority of POPs are shown in serum from a cohort of policemen from Guinea-Bissau. In contrast, the levels of polybrominated diphenyl ethers (PBDEs) show an increasing time trend. Within five years, decreasing levels of POPs were also shown in children working and living at a waste disposal site in Nicaragua. Children working and living at waste disposal sites in Bangladesh have considerably lower levels of POPs compared to the children from Nicaragua except for 4,4’-DDT and 4,4’-DDE that are present at very high concentrations, indicating ongoing use of technical DDT. There are many studies on levels and trends of environmental pollutants from the developed industrial countries in the world, whereas data from developing countries is still scarce. This thesis contributes to partly fill this data gap since it includes assessments of POPs in children and adults from four countries on four continents. / At the time of doctoral defense, the following papers were unpublished and had a status as follows: Paper 5: Manuscript. Paper 6: Manuscript.

Persistent environmental pollutants were examined for their interaction with the glucocorticoid hormone system. The focus was placed on interference with the glucocorticoid synthesis and the glucocorticoid-signalling pathway in various in vitro test systems. Several aryl methyl sulphones competitively inhibited CYP11B1 activity in mouse adrenocortical Y1 cells. The DDT metabolite, 3-methylsulphonyl-2,2’-bis(4-chlorophenyl)-1,1’-dichloroethene (3-MeSO2-DDE) had a higher affinity to the enzyme than the endogenous substrate, 11-deoxycorticosterone. In fact, 3-MeSO2-DDE (Ki 1.6 μM) was almost as potent as the drug metyrapone (Ki 0.8 μM), a well-known inhibitor of the enzyme. 3-MeSO2-DDE inhibited CYP11B1 activity in human adrenocortical H295R carcinoma cells, and at higher concentrations the CYP21 activity. The human H295R cell line seems to be a useful test system for studies of enzyme activities and could be used to screen endocrine disrupting chemicals interfering with the glucocorticoid hormone synthesis. Several chiral PCB methyl sulphones and the fungicide tolylfluanid proved to be antagonists to the glucocorticoid receptor (GR) in rat hepatoma cells and/or Chinese hamster ovary cells stable transformed with a human GR and a responsive reporter vector. The 4-methylsulphonyl-2,3,6,2’,4’,5’-hexachlorobiphenyl (4-MeSO2-CB149) enantiomers had similar antagonistic effect on the GR. Co-exposure of substances led to additive inhibitory effects on glucocorticoid-regulated protein synthesis in rat hepatoma cells. In general, 4-substituted but not 3-substituted methylsulphonyl-PCBs interacted with the glucocorticoid hormone system. In the environment, humans and wildlife are constantly exposed to a wide range of chemicals. Considering the effects of these substances via mechanisms of actions described in this thesis, interference of xenobiotics with the glucocorticoid hormone system deserves further attention. In conclusion, environmental pollutants can interact with the glucocorticoid hormone system in vitro, yet the effects of the tested substances on this hormone system remain to be established in vivo.

A gill filament-based assay for the cytochrome P450 1A (CYP1A)-catalysed activity ethoxyresorufin O-deethylase (EROD) was developed in rainbow trout (Oncorhynchus mykiss) and applied to Atlantic salmon (Salmo salar), Arctic charr (Salvelinus alpinus), Atlantic cod (Gadus morhua), saithe (Pollachius virens), and spotted wolffish (Anarhichas minor). Exposure to waterborne β-naphthoflavone (βNF; 10-6 M) induced branchial EROD activity in all species but the spotted wolffish. In rainbow trout exposed to low concentrations of benzo[a]pyrene (BaP; 10-9 M) and the textile dye indigo (10-8 M) the gills responded more rapidly than the liver to BaP, and indigo induced branchial but not hepatic EROD activity. A CYP1A-dependent BaP adduct formation was shown in gills of fish exposed to waterborne 3H-BaP, i.e. the adduct formation was enhanced by βNF and blocked by ellipticine (CYP1A inhibitor). The predominant location for BaP adducts was the secondary lamellae (most exposed part of the gill filament), whereas the CYP1A enzyme was also present in the primary lamellae of the gill filament. Hence, in addition to the cell-specific expression of CYP1A an important determinant for the localisation of adducts seemed to be the bioavailability of BaP. This idea is supported by the fact that the CYP1A enzyme was induced only in secondary lamellae by BaP (10-7 M) and indigo (10-6 M), whereas it was induced in both primary and secondary lamellae by 3,3´,4,4´,5-pentachlorobiphenyl (10-8 M). Apparently, readily metabolised inducers (BaP and indigo) are biotransformed in the secondary lamellae. My results show that gill filament EROD activity is a sensitive biomarker of exposure to waterborne dioxin-like pollutants, and that the assay has potential for use in monitoring. Furthermore, the results suggest that readily metabolised dioxin-like compounds absorbed via the gills may undergo first-pass metabolism in the gill cells and therefore remain undetected by monitoring of EROD activity in the liver.

Induction of the cytochrome P450(CYP)1A protein and the connected increase in 7-ethoxyresorufin O-deethylase (EROD) activity are common biomarkers in fish. Enhanced activity of this protein signals exposure to Ah-receptor agonists such as chlorinated dioxins, co-planar polychlorinated biphenyls (PCBs) and certain polycyclic aromatic hydrocarbons (PAHs). The EROD biomarker is commonly analyzed in liver microsomes. However, the gill is directly exposed to waterborne pollutants, and in this thesis the gill filament EROD assay was therefore evaluated as a monitoring tool for waterborne CYP1A inducers in fish. Originally developed in rainbow trout (Oncorhynchus mykiss), the assay was here applied in various limnic and marine species. Following exposure to low waterborne concentrations of the readily metabolized CYP1A inducers benzo(a)pyrene (BaP) and indigo, a strong EROD induction was observed in the gill but not in the liver. This likely reflected metabolic clearance of the inducers in gill and other extrahepatic tissues. The high sensitivity of the gill was confirmed in studies of fish caged in waters in urban and rural areas in Sweden where the gill consistently showed a more pronounced EROD induction compared with the liver and the kidney. Fish caged in the reference waters showed surprisingly strong gill EROD induction and CYP1A immunostaining. Consequently, there may be CYP1A inducers present in the aquatic environment that are not yet identified. The assay was further applied in Atlantic cod (Gadus morhua) as a biomarker of exposure to crude oil and produced water (PW) from oil fields in the North Sea. The assay was finally adapted to detect inhibiting compounds, and an imidazole, a triazole and a plant flavonoid turned out to be potent gill EROD inhibitors. The overall conclusion from the studies of this thesis is that the gill filament EROD assay is a practical and sensitive biomarker of exposure to waterborne CYP1A inducers in various fish species. The induction of gill EROD activity in fish also at the reference sites in the field studies calls for further studies on background contamination in Swedish waters.

This thesis investigates the neurotoxic effects in mice neonatally co-exposed to different toxic environmental agents during a defined critical period of the brains's rapid growth and development. Environmental toxic agents are incorporated in our environment. The agents investigated in this thesis are ortho-substituted polychlorinated biphenyls (PCBs 52, and 153), co-planar PCB (PCB 126), polybrominated diphenyl ether (PBDE 99), methyl mercury (MeHg), and γ-radiation. Several epidemiological studies show that human exposure to environmental agents during early development can affect childhood cognitive development. The brain growth spurt (BGS) is defined by rapid growth and development of the immature brain. For rodents (rats and mice) the BGS is postnatal spanning the first 3-4 weeks after birth. For humans this period begins during the third trimester of pregnancy and continues throughout the first two years of life. Several studies have shown that the BGS period of the brain's development renders the brain vunerable and susceptible to insults caused by environmental agents. The combinations of environmental agents used in this thesis were: PCB 52 + PBDE 99, PCB 153 + MeHg, PCB 126 + MeHg, PBDE 99 + MeHg, and γ-radiation + MeHg. The studies presented in this thesis show that co-exposure to low doses of environmental agents lead to interaction effects. These effects of interaction include defective spontaneous behavior, diminished habituation capabilities and hyperactive condition, decreased learning and memory abilities, and reduction in the nicotinic cholinergic receptor densities. Traditionally environmental agents are evaluated one at a time to investigate their effects of toxicity. This thesis indicates that the effects of interaction caused by co-exposure were often seen at doses where exposure to the individual environmental agent alone did not cause any effect. The observed effect of co-exposure were often as pronounced as a dose up to ten times the individual environmental agent alone.