972 resultados para Atypical Mycobacteria


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The hydrodynamics, morphology and sedimentology of the Taperaçu estuary were investigated. This is one of several estuaries located within the largest mangrove fringe in the world, bordering the Amazon region, subject to a macrotidal regime and regionally atypical negligible fresh water supply. The results reveal widespread sand banks that occupy the central portion of the estuarine cross-section. Well-sorted very fine sandy sediments of marine origin prevail. Shorter flood phases, with substantially higher current velocities, were observed in the upper sector of Taperaçu, as expected for a shallow, friction-dominated estuary. However, ebb domination can be expected for estuaries with large associated mangrove areas and substantial estuarine infilling, both of which situations occur on the Taperaçu. The tidal asymmetry favoring flood currents could be the result of the absence of an effective fluvial discharge. Furthermore, it was observed that the Taperaçu is connected by tidal creeks to the neighboring Caeté estuary, allowing a stronger flux during the flood and intensifying the higher flood currents. As a whole, the results have shown a complex interaction of morphological aspects (friction, fluvial drainage, connections with neighbor estuaries, infilling and large storage area) in determining hydrodynamic patterns, thus improving the understanding of Amazon estuaries.

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Abstract: Background: The testis-specific isoform of angiotensin-converting enzyme (tACE) is exclusively expressed in germ cells during spermatogenesis. Although the exact role of tACE in male fertility is unknown, it clearly plays a critical function in spermatogenesis. The dipeptidase domain of tACE is identical to the C-terminal catalytic domain of somatic ACE (sACE). Bradykinin potentiating peptides (BPPs) from snake venoms are the first natural sACE inhibitors described and their structure–activity relationship studies were the basis for the development of antihypertensive drugs such as captopril. In recent years, it has been showed that a number of BPPs – including BPP-10c – are able to distinguish between the N- and C-active sites of sACE, what is not applicable to captopril. Considering the similarity between tACE and sACE (and since BPPs are able to distinguish between the two active sites of sACE), the effects of the BPP-10c and captopril on the structure and function of the seminiferous epithelium were characterized in the present study. BPP-10c and captopril were administered in male Swiss mice by intraperitoneal injection (4.7 μmol/kg for 15 days) and histological sections of testes were analyzed. Classification of seminiferous tubules and stage analysis were carried out for quantitative evaluation of germ cells of the seminiferous epithelium. The blood-testis barrier (BTB) permeability and distribution of claudin-1 in the seminiferous epithelium were analyzed by hypertonic fixative method and immunohistochemical analyses of testes, respectively. Results: The morphology of seminiferous tubules from animals treated with BPP-10c showed an intense disruption of the epithelium, presence of atypical multinucleated cells in the lumen and degenerated germ cells in the adluminal compartment. BPP-10c led to an increase in the number of round spermatids and total support capacity of Sertoli cell in stages I, V, VII/VIII of the seminiferous epithelium cycle, without affecting BTB permeability and the distribution of claudin-1 in the seminiferous epithelium. Interestingly, no morphological or morphometric alterations were observed in animals treated with captopril. Conclusions: The major finding of the present study was that BPP-10c, and not captopril, modifies spermatogenesis by causing hyperplasia of round spermatids in stages I, V, and VII/VIII of the spermatogenic cycle.

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Niemann-Pick disease type C (NP-C) is a rare, progressive, irreversible disease leading to disabling neurological manifestations and premature death. The estimated disease incidence is 1:120,000 live births, but this likely represents an underestimate, as the disease may be under-diagnosed due to its highly heterogeneous presentation. NP-C is characterised by visceral, neurological and psychiatric manifestations that are not specific to the disease and that can be found in other conditions. The aim of this review is to provide non-specialists with an expert-based, detailed description of NP-C signs and symptoms, including how they present in patients and how they can be assessed. Early disease detection should rely on seeking a combination of signs and symptoms, rather than isolated findings. Examples of combinations which are strongly suggestive of NP-C include: splenomegaly and vertical supranuclear gaze palsy (VSGP); splenomegaly and clumsiness; splenomegaly and schizophrenia-like psychosis; psychotic symptoms and cognitive decline; and ataxia with dystonia, dysarthria/dysphagia and cognitive decline. VSGP is a hallmark of NP-C and becomes highly specific of the disease when it occurs in combination with other manifestations (e.g. splenomegaly, ataxia). In young infants (<2 years), abnormal saccades may first manifest as slowing and shortening of upward saccades, long before gaze palsy onset. While visceral manifestations tend to predominate during the perinatal and infantile period (2 months–6 years of age), neurological and psychiatric involvement is more prominent during the juvenile/adult period (>6 years of age). Psychosis in NP-C is atypical and variably responsive to treatment. Progressive cognitive decline, which always occurs in patients with NP-C, manifests as memory and executive impairment in juvenile/adult patients. Disease prognosis mainly correlates with the age at onset of the neurological signs, with early-onset forms progressing faster. Therefore, a detailed and descriptive picture of NP-C signs and symptoms may help improve disease detection and early diagnosis, so that therapy with miglustat (Zavesca®), the only available treatment approved to date, can be started as soon as neurological symptoms appear, in order to slow disease progression.

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The control of gene expression by miRNAs has been widely investigated in different species and cell types. Following a probabilistic rather than a deterministic regimen, the action of these short nucleotide sequences on specific genes depends on intracellular concentration,which in turn reflects the balance between biosynthesis and degradation. Recent studies have described the involvement of XRN2, an exoribonuclease, in miRNA degradation and PAPD4, an atypical poly(A) polymerase, in miRNA stability. Herein, we examined the expression of XRN2 and PAPD4 in developing and adult rat hippocampi. Combining bioinformatics and real-time PCR,we demonstrated that XRN2 and PAPD4 expression is regulated by the uncorrelated action of transcription factors, resulting in distinct gene expression profiles during development. Analyses of nuclei position and nestin labeling revealed that both proteins progressively accumulated during neuronal differentiation, and that they are weakly expressed in immature neurons and absent in glial and endothelial cells. Despite the differences in subcellular localization, both genes were concurrently identified within identical neuronal subpopulations, including specific inhibitory interneurons. Thus, we cope with a singular circumstance in biology: an almost complete intersected expression of functional-opposed genes, reinforcing that their antagonistically driven actions on miRNAs “make sense” if simultaneously present at the same cells. Considering that the transcriptome in the nervous system is finely tuned to physiological processes, it was remarkable that miRNA stability-related genes were oncurrently identified in neurons that play essential roles in cognitive functions such as memory and learning. In summary, this study reveals a possible new mechanism for the control of miRNA expression.

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Primary lung lymphoma is a rare entity accounting for approximately 0.3% of all primary neoplasia of the lung and includes diffuse large B-cell lymphoma (DLBL) and lymphomatoid granulomatosis (LYG). Considering that clinical features may be similar, whereas epidemiology, morphology, and radiological features are different, the authors report a case of a middle-aged man who presented multiple pulmonary nodules in the lower lobes and groundglass opacities scattered bilaterally on computed tomography. Clinically, he presented a consumptive syndrome with respiratory failure and pleurisy, which progressed until death. The autopsy findings were consistent with lymphomatoid granulomatosis (LYG) grade 3/ diffuse large B-cell lymphoma (DLBL). The authors call attention to the difficulty of establishing an accurate diagnosis, mainly when the demonstration of EBV-infected atypical B-cells fails.

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In the present paper, we solve a twist symplectic map for the action of an ergodic magnetic limiter in a large aspect-ratio tokamak. In this model, we study the bifurcation scenarios that occur in the remnants regular islands that co-exist with chaotic magnetic surfaces. The onset of atypical local bifurcations created by secondary shearless tori are identified through numerical profiles of internal rotation number and we observe that their rupture can reduce the usual magnetic field line escape at the tokamak plasma edge.

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BACKGROUND: Aedes aegypti mosquitoes are the main vectors of dengue viruses. Despite global efforts to reduce the prevalence of dengue using integrated vector management strategies, innovative alternatives are necessary to help prevent virus transmission. Detailed characterizations of Ae. aegypti genes and their products provide information about the biology of mosquitoes and may serve as foundations for the design of new vector control methods. FINDINGS: We studied the Ae. aegypti gene, AAEL010714, that encodes a two-domain odorant-binding protein, AaegOBP45. The predicted gene structure and sequence were validated, although single nucleotide polymorphisms were observed. Transcriptional and translational products accumulate in the ovaries of blood fed females and are not detected or are at low abundance in other tissues. CONCLUSIONS: We validated the Ae. aegypti AAEL010714 gene sequence and characterized the expression profile of a two-domain OBP expressed in ovaries. We propose that AaegOBP45 function as a component of the mosquito eggshell.

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This thesis contains four different studies on the dynamics of gender in households and workplaces. The relationship between family life and work life is in focus, particularly in the paper on labour market outcomes after divorce. In the introductory chapter, the Swedish context is briefly described. The description focuses on gender differences in the labour market and in the home. Theories concerning the division of work in the household are discussed, as are two theories on labour market discrimination, viz. taste discrimination and statistical discrimination. The theory part is concluded with a discussion of social closure processes and gendered organizational structures. The Reproduction of Gender. Housework and Attitudes Towards Gender Equality in the Home Among Swedish Boys and Girls. The housework boys and girls age 10 to 18 do, and their attitudes towards gender equality in the home are studied. One aim is to see whether the work children do is gendered and if so, whether they follow their parents’, often gendered, pattern in housework. A second aim is to see whether parents’ division of work is related to the children’s attitude towards gender equality in the home. The data used are taken from the Swedish Child Level of Living Survey (Child-LNU) 2000. Results indicate that girls and boys in two-parent families are more prone to engage in gender-atypical work the more their parent of the same sex engages in this kind of work. The fact that girls still do more housework than boys indicates that housework is gendered work also among children. No relation between parents’ division of work and the child’s attitude towards gender equality in the home was found. Dependence within Families and the Household Division of Labor – A Comparison between Sweden and the United States. This paper assesses the relative explanatory value of the resource-bargaining perspective and the doing-gender approach in analysing the division of housework in the United States and Sweden from the mid-1970s to 2000. Data from the Swedish Level of Living Survey (LNU) and the Panel Study of Income Dynamics (PSID) were used. Overall results indicate that housework is truly gendered work in both countries during the entire period. Even so, the results also indicate that gender deviance neutralization is more pronounced in the United States than in Sweden. Unlike Swedish women, American women seem to increase their time spent in housework when their husbands are to some extent economically dependent on them, as if to neutralize the presumed gender deviance. Divorce and Labour Market Outcomes. Do Women Suffer or Gain? In this paper, the interconnected nature of work and family is studied by looking at labour market outcomes after divorce. The data used are retrospective work and family histories collected in LNU 1991. A hazard regression model with competing risks reveals that women’s chances of improving their occupational prestige appear to be better after divorce compared to before. Increased working hours and perhaps also increased energy invested in the job may pay off in better occupational opportunities. Worth noting, however, is that the outcome among women with a less firm labour market attachment is more often to a job of lower prestige than one of higher prestige. Hence, the labour market outcome for women after divorce is to some extent conditioned by their labour market attachment at the time of divorce. Men, on the other hand, in most cases seem to suffer occupationally from divorce. For separated men the risk of negative changes in occupational prestige is greater than for cohabiting men. Formal On-the-job Training. A Gender-Typed Experience and Wage- Related Advantage? Formal on-the-job training (FOJT) can have a positive impact on wages and on promotion opportunities. According to theory and earlier research, a two-step model of gender inequality in FOJT is predicted: First, women are less likely than men to take part in FOJT and, second, once women do get the more remunerative training, they are not rewarded for their new skills to the same extent as men are. Pooled cross-sectional data from the Swedish Survey of Living Conditions (ULF) in the mid-nineties were used. Results show that women are significantly less likely than men to take part in FOJT. Among those who do receive training, women are more likely to take part in industry-specific training, whereas men are more likely to participate in general training and training that increases promotion opportunities. The two latter forms of training significantly raise a man’s annual earnings but not a woman’s. Hence, the theoretical model is supported and it is argued that this gender inequality is partly due to employers’ discriminatory practices.

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The ideal approach for the long term treatment of intestinal disorders, such as inflammatory bowel disease (IBD), is represented by a safe and well tolerated therapy able to reduce mucosal inflammation and maintain homeostasis of the intestinal microbiota. A combined therapy with antimicrobial agents, to reduce antigenic load, and immunomodulators, to ameliorate the dysregulated responses, followed by probiotic supplementation has been proposed. Because of the complementary mechanisms of action of antibiotics and probiotics, a combined therapeutic approach would give advantages in terms of enlargement of the antimicrobial spectrum, due to the barrier effect of probiotic bacteria, and limitation of some side effects of traditional chemiotherapy (i.e. indiscriminate decrease of aggressive and protective intestinal bacteria, altered absorption of nutrient elements, allergic and inflammatory reactions). Rifaximin (4-deoxy-4’-methylpyrido[1’,2’-1,2]imidazo[5,4-c]rifamycin SV) is a product of synthesis experiments designed to modify the parent compound, rifamycin, in order to achieve low gastrointestinal absorption while retaining good antibacterial activity. Both experimental and clinical pharmacology clearly show that this compound is a non systemic antibiotic with a broad spectrum of antibacterial action, covering Gram-positive and Gram-negative organisms, both aerobes and anaerobes. Being virtually non absorbed, its bioavailability within the gastrointestinal tract is rather high with intraluminal and faecal drug concentrations that largely exceed the MIC values observed in vitro against a wide range of pathogenic microorganisms. The gastrointestinal tract represents therefore the primary therapeutic target and gastrointestinal infections the main indication. The little value of rifaximin outside the enteric area minimizes both antimicrobial resistance and systemic adverse events. Fermented dairy products enriched with probiotic bacteria have developed into one of the most successful categories of functional foods. Probiotics are defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host” (FAO/WHO, 2002), and mainly include Lactobacillus and Bifidobacterium species. Probiotic bacteria exert a direct effect on the intestinal microbiota of the host and contribute to organoleptic, rheological and nutritional properties of food. Administration of pharmaceutical probiotic formula has been associated with therapeutic effects in treatment of diarrhoea, constipation, flatulence, enteropathogens colonization, gastroenteritis, hypercholesterolemia, IBD, such as ulcerative colitis (UC), Crohn’s disease, pouchitis and irritable bowel syndrome. Prerequisites for probiotics are to be effective and safe. The characteristics of an effective probiotic for gastrointestinal tract disorders are tolerance to upper gastrointestinal environment (resistance to digestion by enteric or pancreatic enzymes, gastric acid and bile), adhesion on intestinal surface to lengthen the retention time, ability to prevent the adherence, establishment and/or replication of pathogens, production of antimicrobial substances, degradation of toxic catabolites by bacterial detoxifying enzymatic activities, and modulation of the host immune responses. This study was carried out using a validated three-stage fermentative continuous system and it is aimed to investigate the effect of rifaximin on the colonic microbial flora of a healthy individual, in terms of bacterial composition and production of fermentative metabolic end products. Moreover, this is the first study that investigates in vitro the impact of the simultaneous administration of the antibiotic rifaximin and the probiotic B. lactis BI07 on the intestinal microbiota. Bacterial groups of interest were evaluated using culture-based methods and molecular culture-independent techniques (FISH, PCR-DGGE). Metabolic outputs in terms of SCFA profiles were determined by HPLC analysis. Collected data demonstrated that rifaximin as well as antibiotic and probiotic treatment did not change drastically the intestinal microflora, whereas bacteria belonging to Bifidobacterium and Lactobacillus significantly increase over the course of the treatment, suggesting a spontaneous upsurge of rifaximin resistance. These results are in agreement with a previous study, in which it has been demonstrated that rifaximin administration in patients with UC, affects the host with minor variations of the intestinal microflora, and that the microbiota is restored over a wash-out period. In particular, several Bifidobacterium rifaximin resistant mutants could be isolated during the antibiotic treatment, but they disappeared after the antibiotic suspension. Furthermore, bacteria belonging to Atopobium spp. and E. rectale/Clostridium cluster XIVa increased significantly after rifaximin and probiotic treatment. Atopobium genus and E. rectale/Clostridium cluster XIVa are saccharolytic, butyrate-producing bacteria, and for these characteristics they are widely considered health-promoting microorganisms. The absence of major variations in the intestinal microflora of a healthy individual and the significant increase in probiotic and health-promoting bacteria concentrations support the rationale of the administration of rifaximin as efficacious and non-dysbiosis promoting therapy and suggest the efficacy of an antibiotic/probiotic combined treatment in several gut pathologies, such as IBD. To assess the use of an antibiotic/probiotic combination for clinical management of intestinal disorders, genetic, proteomic and physiologic approaches were employed to elucidate molecular mechanisms determining rifaximin resistance in Bifidobacterium, and the expected interactions occurring in the gut between these bacteria and the drug. The ability of an antimicrobial agent to select resistance is a relevant factor that affects its usefulness and may diminish its useful life. Rifaximin resistance phenotype was easily acquired by all bifidobacteria analyzed [type strains of the most representative intestinal bifidobacterial species (B. infantis, B. breve, B. longum, B. adolescentis and B. bifidum) and three bifidobacteria included in a pharmaceutical probiotic preparation (B. lactis BI07, B. breve BBSF and B. longum BL04)] and persisted for more than 400 bacterial generations in the absence of selective pressure. Exclusion of any reversion phenomenon suggested two hypotheses: (i) stable and immobile genetic elements encode resistance; (ii) the drug moiety does not act as an inducer of the resistance phenotype, but enables selection of resistant mutants. Since point mutations in rpoB have been indicated as representing the principal factor determining rifampicin resistance in E. coli and M. tuberculosis, whether a similar mechanism also occurs in Bifidobacterium was verified. The analysis of a 129 bp rpoB core region of several wild-type and resistant bifidobacteria revealed five different types of miss-sense mutations in codons 513, 516, 522 and 529. Position 529 was a novel mutation site, not previously described, and position 522 appeared interesting for both the double point substitutions and the heterogeneous profile of nucleotide changes. The sequence heterogeneity of codon 522 in Bifidobacterium leads to hypothesize an indirect role of its encoded amino acid in the binding with the rifaximin moiety. These results demonstrated the chromosomal nature of rifaximin resistance in Bifidobacterium, minimizing risk factors for horizontal transmission of resistance elements between intestinal microbial species. Further proteomic and physiologic investigations were carried out using B. lactis BI07, component of a pharmaceutical probiotic preparation, as a model strain. The choice of this strain was determined based on the following elements: (i) B. lactis BI07 is able to survive and persist in the gut; (ii) a proteomic overview of this strain has been recently reported. The involvement of metabolic changes associated with rifaximin resistance was investigated by proteomic analysis performed with two-dimensional electrophoresis and mass spectrometry. Comparative proteomic mapping of BI07-wt and BI07-res revealed that most differences in protein expression patterns were genetically encoded rather than induced by antibiotic exposure. In particular, rifaximin resistance phenotype was characterized by increased expression levels of stress proteins. Overexpression of stress proteins was expected, as they represent a common non specific response by bacteria when stimulated by different shock conditions, including exposure to toxic agents like heavy metals, oxidants, acids, bile salts and antibiotics. Also, positive transcription regulators were found to be overexpressed in BI07-res, suggesting that bacteria could activate compensatory mechanisms to assist the transcription process in the presence of RNA polymerase inhibitors. Other differences in expression profiles were related to proteins involved in central metabolism; these modifications suggest metabolic disadvantages of resistant mutants in comparison with sensitive bifidobacteria in the gut environment, without selective pressure, explaining their disappearance from faeces of patients with UC after interruption of antibiotic treatment. The differences observed between BI07-wt e BI07-res proteomic patterns, as well as the high frequency of silent mutations reported for resistant mutants of Bifidobacterium could be the consequences of an increased mutation rate, mechanism which may lead to persistence of resistant bacteria in the population. However, the in vivo disappearance of resistant mutants in absence of selective pressure, allows excluding the upsurge of compensatory mutations without loss of resistance. Furthermore, the proteomic characterization of the resistant phenotype suggests that rifaximin resistance is associated with a reduced bacterial fitness in B. lactis BI07-res, supporting the hypothesis of a biological cost of antibiotic resistance in Bifidobacterium. The hypothesis of rifaximin inactivation by bacterial enzymatic activities was verified by using liquid chromatography coupled with tandem mass spectrometry. Neither chemical modifications nor degradation derivatives of the rifaximin moiety were detected. The exclusion of a biodegradation pattern for the drug was further supported by the quantitative recovery in BI07-res culture fractions of the total rifaximin amount (100 μg/ml) added to the culture medium. To confirm the main role of the mutation on the β chain of RNA polymerase in rifaximin resistance acquisition, transcription activity of crude enzymatic extracts of BI07-res cells was evaluated. Although the inhibition effects of rifaximin on in vitro transcription were definitely higher for BI07-wt than for BI07-res, a partial resistance of the mutated RNA polymerase at rifaximin concentrations > 10 μg/ml was supposed, on the basis of the calculated differences in inhibition percentages between BI07-wt and BI07-res. By considering the resistance of entire BI07-res cells to rifaximin concentrations > 100 μg/ml, supplementary resistance mechanisms may take place in vivo. A barrier for the rifaximin uptake in BI07-res cells was suggested in this study, on the basis of the major portion of the antibiotic found to be bound to the cellular pellet respect to the portion recovered in the cellular lysate. Related to this finding, a resistance mechanism involving changes of membrane permeability was supposed. A previous study supports this hypothesis, demonstrating the involvement of surface properties and permeability in natural resistance to rifampicin in mycobacteria, isolated from cases of human infection, which possessed a rifampicin-susceptible RNA polymerase. To understand the mechanism of membrane barrier, variations in percentage of saturated and unsaturated FAs and their methylation products in BI07-wt and BI07-res membranes were investigated. While saturated FAs confer rigidity to membrane and resistance to stress agents, such as antibiotics, a high level of lipid unsaturation is associated with high fluidity and susceptibility to stresses. Thus, the higher percentage of saturated FAs during the stationary phase of BI07-res could represent a defence mechanism of mutant cells to prevent the antibiotic uptake. Furthermore, the increase of CFAs such as dihydrosterculic acid during the stationary phase of BI07-res suggests that this CFA could be more suitable than its isomer lactobacillic acid to interact with and prevent the penetration of exogenous molecules including rifaximin. Finally, the impact of rifaximin on immune regulatory functions of the gut was evaluated. It has been suggested a potential anti-inflammatory effect of rifaximin, with reduced secretion of IFN-γ in a rodent model of colitis. Analogously, it has been reported a significant decrease in IL-8, MCP-1, MCP-3 e IL-10 levels in patients affected by pouchitis, treated with a combined therapy of rifaximin and ciprofloxacin. Since rifaximin enables in vivo and in vitro selection of Bifidobacterium resistant mutants with high frequency, the immunomodulation activities of rifaximin associated with a B. lactis resistant mutant were also taken into account. Data obtained from PBMC stimulation experiments suggest the following conclusions: (i) rifaximin does not exert any effect on production of IL-1β, IL-6 and IL-10, whereas it weakly stimulates production of TNF-α; (ii) B. lactis appears as a good inducer of IL-1β, IL-6 and TNF-α; (iii) combination of BI07-res and rifaximin exhibits a lower stimulation effect than BI07-res alone, especially for IL-6. These results confirm the potential anti-inflammatory effect of rifaximin, and are in agreement with several studies that report a transient pro-inflammatory response associated with probiotic administration. The understanding of the molecular factors determining rifaximin resistance in the genus Bifidobacterium assumes an applicative significance at pharmaceutical and medical level, as it represents the scientific basis to justify the simultaneous use of the antibiotic rifaximin and probiotic bifidobacteria in the clinical treatment of intestinal disorders.

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Introduction 1.1 Occurrence of polycyclic aromatic hydrocarbons (PAH) in the environment Worldwide industrial and agricultural developments have released a large number of natural and synthetic hazardous compounds into the environment due to careless waste disposal, illegal waste dumping and accidental spills. As a result, there are numerous sites in the world that require cleanup of soils and groundwater. Polycyclic aromatic hydrocarbons (PAHs) are one of the major groups of these contaminants (Da Silva et al., 2003). PAHs constitute a diverse class of organic compounds consisting of two or more aromatic rings with various structural configurations (Prabhu and Phale, 2003). Being a derivative of benzene, PAHs are thermodynamically stable. In addition, these chemicals tend to adhere to particle surfaces, such as soils, because of their low water solubility and strong hydrophobicity, and this results in greater persistence under natural conditions. This persistence coupled with their potential carcinogenicity makes PAHs problematic environmental contaminants (Cerniglia, 1992; Sutherland, 1992). PAHs are widely found in high concentrations at many industrial sites, particularly those associated with petroleum, gas production and wood preserving industries (Wilson and Jones, 1993). 1.2 Remediation technologies Conventional techniques used for the remediation of soil polluted with organic contaminants include excavation of the contaminated soil and disposal to a landfill or capping - containment - of the contaminated areas of a site. These methods have some drawbacks. The first method simply moves the contamination elsewhere and may create significant risks in the excavation, handling and transport of hazardous material. Additionally, it is very difficult and increasingly expensive to find new landfill sites for the final disposal of the material. The cap and containment method is only an interim solution since the contamination remains on site, requiring monitoring and maintenance of the isolation barriers long into the future, with all the associated costs and potential liability. A better approach than these traditional methods is to completely destroy the pollutants, if possible, or transform them into harmless substances. Some technologies that have been used are high-temperature incineration and various types of chemical decomposition (for example, base-catalyzed dechlorination, UV oxidation). However, these methods have significant disadvantages, principally their technological complexity, high cost , and the lack of public acceptance. Bioremediation, on the contrast, is a promising option for the complete removal and destruction of contaminants. 1.3 Bioremediation of PAH contaminated soil & groundwater Bioremediation is the use of living organisms, primarily microorganisms, to degrade or detoxify hazardous wastes into harmless substances such as carbon dioxide, water and cell biomass Most PAHs are biodegradable unter natural conditions (Da Silva et al., 2003; Meysami and Baheri, 2003) and bioremediation for cleanup of PAH wastes has been extensively studied at both laboratory and commercial levels- It has been implemented at a number of contaminated sites, including the cleanup of the Exxon Valdez oil spill in Prince William Sound, Alaska in 1989, the Mega Borg spill off the Texas coast in 1990 and the Burgan Oil Field, Kuwait in 1994 (Purwaningsih, 2002). Different strategies for PAH bioremediation, such as in situ , ex situ or on site bioremediation were developed in recent years. In situ bioremediation is a technique that is applied to soil and groundwater at the site without removing the contaminated soil or groundwater, based on the provision of optimum conditions for microbiological contaminant breakdown.. Ex situ bioremediation of PAHs, on the other hand, is a technique applied to soil and groundwater which has been removed from the site via excavation (soil) or pumping (water). Hazardous contaminants are converted in controlled bioreactors into harmless compounds in an efficient manner. 1.4 Bioavailability of PAH in the subsurface Frequently, PAH contamination in the environment is occurs as contaminants that are sorbed onto soilparticles rather than in phase (NAPL, non aqueous phase liquids). It is known that the biodegradation rate of most PAHs sorbed onto soil is far lower than rates measured in solution cultures of microorganisms with pure solid pollutants (Alexander and Scow, 1989; Hamaker, 1972). It is generally believed that only that fraction of PAHs dissolved in the solution can be metabolized by microorganisms in soil. The amount of contaminant that can be readily taken up and degraded by microorganisms is defined as bioavailability (Bosma et al., 1997; Maier, 2000). Two phenomena have been suggested to cause the low bioavailability of PAHs in soil (Danielsson, 2000). The first one is strong adsorption of the contaminants to the soil constituents which then leads to very slow release rates of contaminants to the aqueous phase. Sorption is often well correlated with soil organic matter content (Means, 1980) and significantly reduces biodegradation (Manilal and Alexander, 1991). The second phenomenon is slow mass transfer of pollutants, such as pore diffusion in the soil aggregates or diffusion in the organic matter in the soil. The complex set of these physical, chemical and biological processes is schematically illustrated in Figure 1. As shown in Figure 1, biodegradation processes are taking place in the soil solution while diffusion processes occur in the narrow pores in and between soil aggregates (Danielsson, 2000). Seemingly contradictory studies can be found in the literature that indicate the rate and final extent of metabolism may be either lower or higher for sorbed PAHs by soil than those for pure PAHs (Van Loosdrecht et al., 1990). These contrasting results demonstrate that the bioavailability of organic contaminants sorbed onto soil is far from being well understood. Besides bioavailability, there are several other factors influencing the rate and extent of biodegradation of PAHs in soil including microbial population characteristics, physical and chemical properties of PAHs and environmental factors (temperature, moisture, pH, degree of contamination). Figure 1: Schematic diagram showing possible rate-limiting processes during bioremediation of hydrophobic organic contaminants in a contaminated soil-water system (not to scale) (Danielsson, 2000). 1.5 Increasing the bioavailability of PAH in soil Attempts to improve the biodegradation of PAHs in soil by increasing their bioavailability include the use of surfactants , solvents or solubility enhancers.. However, introduction of synthetic surfactant may result in the addition of one more pollutant. (Wang and Brusseau, 1993).A study conducted by Mulder et al. showed that the introduction of hydropropyl-ß-cyclodextrin (HPCD), a well-known PAH solubility enhancer, significantly increased the solubilization of PAHs although it did not improve the biodegradation rate of PAHs (Mulder et al., 1998), indicating that further research is required in order to develop a feasible and efficient remediation method. Enhancing the extent of PAHs mass transfer from the soil phase to the liquid might prove an efficient and environmentally low-risk alternative way of addressing the problem of slow PAH biodegradation in soil.

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This study aims at analysing Brian O'Nolans literary production in the light of a reconsideration of the role played by his two most famous pseudonyms ,Flann Brien and Myles na Gopaleen, behind which he was active both as a novelist and as a journalist. We tried to establish a new kind of relationship between them and their empirical author following recent cultural and scientific surveys in the field of Humour Studies, Psychology, and Sociology: taking as a starting point the appreciation of the comic attitude in nature and in cultural history, we progressed through a short history of laughter and derision, followed by an overview on humour theories. After having established such a frame, we considered an integration of scientific studies in the field of laughter and humour as a base for our study scheme, in order to come to a definition of the comic author as a recognised, powerful and authoritative social figure who acts as a critic of conventions. The history of laughter and comic we briefly summarized, based on the one related by the French scholar Georges Minois in his work (Minois 2004), has been taken into account in the view that humorous attitude is one of man’s characteristic traits always present and witnessed throughout the ages, though subject in most cases to repression by cultural and political conservative power. This sort of Super-Ego notwithstanding, or perhaps because of that, comic impulse proved irreducible exactly in its influence on the current cultural debates. Basing mainly on Robert R. Provine’s (Provine 2001), Fabio Ceccarelli’s (Ceccarelli 1988), Arthur Koestler’s (Koestler 1975) and Peter L. Berger’s (Berger 1995) scientific essays on the actual occurrence of laughter and smile in complex social situations, we underlined the many evidences for how the use of comic, humour and wit (in a Freudian sense) could be best comprehended if seen as a common mind process designed for the improvement of knowledge, in which we traced a strict relation with the play-element the Dutch historian Huizinga highlighted in his famous essay, Homo Ludens (Huizinga 1955). We considered comic and humour/wit as different sides of the same coin, and showed how the demonstrations scientists provided on this particular subject are not conclusive, given that the mental processes could not still be irrefutably shown to be separated as regards graduations in comic expression and reception: in fact, different outputs in expressions might lead back to one and the same production process, following the general ‘Economy Rule’ of evolution; man is the only animal who lies, meaning with this that one feeling is not necessarily biuniquely associated with one and the same outward display, so human expressions are not validation proofs for feelings. Considering societies, we found that in nature they are all organized in more or less the same way, that is, in élites who govern over a community who, in turn, recognizes them as legitimate delegates for that task; we inferred from this the epistemological possibility for the existence of an added ruling figure alongside those political and religious: this figure being the comic, who is the person in charge of expressing true feelings towards given subjects of contention. Any community owns one, and his very peculiar status is validated by the fact that his place is within the community, living in it and speaking to it, but at the same time is outside it in the sense that his action focuses mainly on shedding light on ideas and objects placed out-side the boundaries of social convention: taboos, fears, sacred objects and finally culture are the favourite targets of the comic person’s arrow. This is the reason for the word a(rche)typical as applied to the comic figure in society: atypical in a sense, because unconventional and disrespectful of traditions, critical and never at ease with unblinkered respect of canons; archetypical, because the “village fool”, buffoon, jester or anyone in any kind of society who plays such roles, is an archetype in the Jungian sense, i.e. a personification of an irreducible side of human nature that everybody instinctively knows: a beginner of a tradition, the perfect type, what is most conventional of all and therefore the exact opposite of an atypical. There is an intrinsic necessity, we think, of such figures in societies, just like politicians and priests, who should play an elitist role in order to guide and rule not for their own benefit but for the good of the community. We are not naïve and do know that actual owners of power always tend to keep it indefinitely: the ‘social comic’ as a role of power has nonetheless the distinctive feature of being the only job whose tension is not towards stability. It has got in itself the rewarding permission of contradiction, for the very reason we exposed before that the comic must cast an eye both inside and outside society and his vision may be perforce not consistent, then it is satisfactory for the popularity that gives amongst readers and audience. Finally, the difference between governors, priests and comic figures is the seriousness of the first two (fundamentally monologic) and the merry contradiction of the third (essentially dialogic). MPs, mayors, bishops and pastors should always console, comfort and soothe popular mood in respect of the public convention; the comic has the opposite task of provoking, urging and irritating, accomplishing at the same time a sort of control of the soothing powers of society, keepers of the righteousness. In this view, the comic person assumes a paramount importance in the counterbalancing of power administration, whether in form of acting in public places or in written pieces which could circulate for private reading. At this point comes into question our Irish writer Brian O'Nolan(1911-1966), real name that stood behind the more famous masks of Flann O'Brien, novelist, author of At Swim-Two-Birds (1939), The Hard Life (1961), The Dalkey Archive (1964) and, posthumously, The Third Policeman (1967); and of Myles na Gopaleen, journalist, keeper for more than 25 years of the Cruiskeen Lawn column on The Irish Times (1940-1966), and author of the famous book-parody in Irish An Béal Bocht (1941), later translated in English as The Poor Mouth (1973). Brian O'Nolan, professional senior civil servant of the Republic, has never seen recognized his authorship in literary studies, since all of them concentrated on his alter egos Flann, Myles and some others he used for minor contributions. So far as we are concerned, we think this is the first study which places the real name in the title, this way acknowledging him an unity of intents that no-one before did. And this choice in titling is not a mere mark of distinction for the sake of it, but also a wilful sign of how his opus should now be reconsidered. In effect, the aim of this study is exactly that of demonstrating how the empirical author Brian O'Nolan was the real Deus in machina, the master of puppets who skilfully directed all of his identities in planned directions, so as to completely fulfil the role of the comic figure we explained before. Flann O'Brien and Myles na Gopaleen were personae and not persons, but the impression one gets from the critical studies on them is the exact opposite. Literary consideration, that came only after O'Nolans death, began with Anne Clissmann’s work, Flann O'Brien: A Critical Introduction to His Writings (Clissmann 1975), while the most recent book is Keith Donohue’s The Irish Anatomist: A Study of Flann O'Brien (Donohue 2002); passing through M.Keith Booker’s Flann O'Brien, Bakhtin and Menippean Satire (Booker 1995), Keith Hopper’s Flann O'Brien: A Portrait of the Artist as a Young Post-Modernist (Hopper 1995) and Monique Gallagher’s Flann O'Brien, Myles et les autres (Gallagher 1998). There have also been a couple of biographies, which incidentally somehow try to explain critical points his literary production, while many critical studies do the same on the opposite side, trying to found critical points of view on the author’s restless life and habits. At this stage, we attempted to merge into O'Nolan's corpus the journalistic articles he wrote, more than 4,200, for roughly two million words in the 26-year-old running of the column. To justify this, we appealed to several considerations about the figure O'Nolan used as writer: Myles na Gopaleen (later simplified in na Gopaleen), who was the equivalent of the street artist or storyteller, speaking to his imaginary public and trying to involve it in his stories, quarrels and debates of all kinds. First of all, he relied much on language for the reactions he would obtain, playing on, and with, words so as to ironically unmask untrue relationships between words and things. Secondly, he pushed to the limit the convention of addressing to spectators and listeners usually employed in live performing, stretching its role in the written discourse to come to a greater effect of involvement of readers. Lastly, he profited much from what we labelled his “specific weight”, i.e. the potential influence in society given by his recognised authority in determined matters, a position from which he could launch deeper attacks on conventional beliefs, so complying with the duty of a comic we hypothesised before: that of criticising society even in threat of losing the benefits the post guarantees. That seemingly masochistic tendency has its rationale. Every representative has many privileges on the assumption that he, or she, has great responsibilities in administrating. The higher those responsibilities are, the higher is the reward but also the severer is the punishment for the misfits done while in charge. But we all know that not everybody accepts the rules and many try to use their power for their personal benefit and do not want to undergo law’s penalties. The comic, showing in this case more civic sense than others, helped very much in this by the non-accessibility to the use of public force, finds in the role of the scapegoat the right accomplishment of his task, accepting the punishment when his breaking of the conventions is too stark to be forgiven. As Ceccarelli demonstrated, the role of the object of laughter (comic, ridicule) has its very own positive side: there is freedom of expression for the person, and at the same time integration in the society, even though at low levels. Then the banishment of a ‘social’ comic can never get to total extirpation from society, revealing how the scope of the comic lies on an entirely fictional layer, bearing no relation with facts, nor real consequences in terms of physical health. Myles na Gopaleen, mastering these three characteristics we postulated in the highest way, can be considered an author worth noting; and the oeuvre he wrote, the whole collection of Cruiskeen Lawn articles, is rightfully a novel because respects the canons of it especially regarding the authorial figure and his relationship with the readers. In addition, his work can be studied even if we cannot conduct our research on the whole of it, this proceeding being justified exactly because of the resemblances to the real figure of the storyteller: its ‘chapters’ —the daily articles— had a format that even the distracted reader could follow, even one who did not read each and every article before. So we can critically consider also a good part of them, as collected in the seven volumes published so far, with the addition of some others outside the collections, because completeness in this case is not at all a guarantee of a better precision in the assessment; on the contrary: examination of the totality of articles might let us consider him as a person and not a persona. Once cleared these points, we proceeded further in considering tout court the works of Brian O'Nolan as the works of a unique author, rather than complicating the references with many names which are none other than well-wrought sides of the same personality. By putting O'Nolan as the correct object of our research, empirical author of the works of the personae Flann O'Brien and Myles na Gopaleen, there comes out a clearer literary landscape: the comic author Brian O'Nolan, self-conscious of his paramount role in society as both a guide and a scourge, in a word as an a(rche)typical, intentionally chose to differentiate his personalities so as to create different perspectives in different fields of knowledge by using, in addition, different means of communication: novels and journalism. We finally compared the newly assessed author Brian O'Nolan with other great Irish comic writers in English, such as James Joyce (the one everybody named as the master in the field), Samuel Beckett, and Jonathan Swift. This comparison showed once more how O'Nolan is in no way inferior to these authors who, greatly celebrated by critics, have nonetheless failed to achieve that great public recognition O’Nolan received alias Myles, awarded by the daily audience he reached and influenced with his Cruiskeen Lawn column. For this reason, we believe him to be representative of the comic figure’s function as a social regulator and as a builder of solidarity, such as that Raymond Williams spoke of in his work (Williams 1982), with in mind the aim of building a ‘culture in common’. There is no way for a ‘culture in common’ to be acquired if we do not accept the fact that even the most functional society rests on conventions, and in a world more and more ‘connected’ we need someone to help everybody negotiate with different cultures and persons. The comic gives us a worldly perspective which is at the same time comfortable and distressing but in the end not harmful as the one furnished by politicians could be: he lets us peep into parallel worlds without moving too far from our armchair and, as a consequence, is the one who does his best for the improvement of our understanding of things.

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This thesis is the result of my experience as a PhD student taking part in the Joint Doctoral Programme at the University of York and the University of Bologna. In my thesis I deal with topics that are of particular interest in Italy and in Great Britain. Chapter 2 focuses on the empirical test of the existence of the relationship between technological profiles and market structure claimed by Sutton’s theory (1991, 1998) in the specific economic framework of hospital care services provided by the Italian National Health Service (NHS). In order to test the empirical predictions by Sutton, we identify the relevant markets for hospital care services in Italy in terms of both product and geographic dimensions. In particular, the Elzinga and Hogarty (1978) approach has been applied to data on patients’ flows across Italian Provinces in order to derive the geographic dimension of each market. Our results provide evidence in favour of the empirical predictions of Sutton. Chapter 3 deals with the patient mobility in the Italian NHS. To analyse the determinants of patient mobility across Local Health Authorities, we estimate gravity equations in multiplicative form using a Poisson pseudo maximum likelihood method, as proposed by Santos-Silva and Tenreyro (2006). In particular, we focus on the scale effect played by the size of the pool of enrolees. In most of the cases our results are consistent with the predictions of the gravity model. Chapter 4 considers the effects of contractual and working conditions on selfassessed health and psychological well-being (derived from the General Health Questionnaire) using the British Household Panel Survey (BHPS). We consider two branches of the literature. One suggests that “atypical” contractual conditions have a significant impact on health while the other suggests that health is damaged by adverse working conditions. The main objective of our paper is to combine the two branches of the literature to assess the distinct effects of contractual and working conditions on health. The results suggest that both sets of conditions have some influence on health and psychological well-being of employees.

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Great strides have been made in the last few years in the pharmacological treatment of neuropsychiatric disorders, with the introduction into the therapy of several new and more efficient agents, which have improved the quality of life of many patients. Despite these advances, a large percentage of patients is still considered “non-responder” to the therapy, not drawing any benefits from it. Moreover, these patients have a peculiar therapeutic profile, due to the very frequent application of polypharmacy, attempting to obtain satisfactory remission of the multiple aspects of psychiatric syndromes. Therapy is heavily individualised and switching from one therapeutic agent to another is quite frequent. One of the main problems of this situation is the possibility of unwanted or unexpected pharmacological interactions, which can occur both during polypharmacy and during switching. Simultaneous administration of psychiatric drugs can easily lead to interactions if one of the administered compounds influences the metabolism of the others. Impaired CYP450 function due to inhibition of the enzyme is frequent. Other metabolic pathways, such as glucuronidation, can also be influenced. The Therapeutic Drug Monitoring (TDM) of psychotropic drugs is an important tool for treatment personalisation and optimisation. It deals with the determination of parent drugs and metabolites plasma levels, in order to monitor them over time and to compare these findings with clinical data. This allows establishing chemical-clinical correlations (such as those between administered dose and therapeutic and side effects), which are essential to obtain the maximum therapeutic efficacy, while minimising side and toxic effects. It is evident the importance of developing sensitive and selective analytical methods for the determination of the administered drugs and their main metabolites, in order to obtain reliable data that can correctly support clinical decisions. During the three years of Ph.D. program, some analytical methods based on HPLC have been developed, validated and successfully applied to the TDM of psychiatric patients undergoing treatment with drugs belonging to following classes: antipsychotics, antidepressants and anxiolytic-hypnotics. The biological matrices which have been processed were: blood, plasma, serum, saliva, urine, hair and rat brain. Among antipsychotics, both atypical and classical agents have been considered, such as haloperidol, chlorpromazine, clotiapine, loxapine, risperidone (and 9-hydroxyrisperidone), clozapine (as well as N-desmethylclozapine and clozapine N-oxide) and quetiapine. While the need for an accurate TDM of schizophrenic patients is being increasingly recognized by psychiatrists, only in the last few years the same attention is being paid to the TDM of depressed patients. This is leading to the acknowledgment that depression pharmacotherapy can greatly benefit from the accurate application of TDM. For this reason, the research activity has also been focused on first and second-generation antidepressant agents, like triciclic antidepressants, trazodone and m-chlorophenylpiperazine (m-cpp), paroxetine and its three main metabolites, venlafaxine and its active metabolite, and the most recent antidepressant introduced into the market, duloxetine. Among anxiolytics-hypnotics, benzodiazepines are very often involved in the pharmacotherapy of depression for the relief of anxious components; for this reason, it is useful to monitor these drugs, especially in cases of polypharmacy. The results obtained during these three years of Ph.D. program are reliable and the developed HPLC methods are suitable for the qualitative and quantitative determination of CNS drugs in biological fluids for TDM purposes.

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The Myc oncoproteins belong to a family of transcription factors composed by Myc, N-Myc and L-Myc. The most studied components of this family are Myc and N-Myc because their expressions are frequently deregulated in a wide range of cancers. These oncoproteins can act both as activators or repressors of gene transcription. As activators, they heterodimerize with Max (Myc associated X-factor) and the heterodimer recognizes and binds a specific sequence elements (E-Box) onto gene promoters recruiting histone acetylase and inducing transcriptional activation. Myc-mediated transcriptional repression is a quite debated issue. One of the first mechanisms defined for the Myc-mediated transcriptional repression consisted in the interaction of Myc-Max complex Sp1 and/or Miz1 transcription factors already bound to gene promoters. This interaction may interfere with their activation functions by recruiting co-repressors such as Dnmt3 or HDACs. Moreover, in the absence of , Myc may interfere with the Sp1 activation function by direct interaction and subsequent recruitment of HDACs. More recently the Myc/Max complex was also shown to mediate transcriptional repression by direct binding to peculiar E-box. In this study we analyzed the role of Myc overexpression in Osteosarcoma and Neuroblastoma oncogenesis and the mechanisms underling to Myc function. Myc overexpression is known to correlate with chemoresistance in Osteosarcoma cells. We extended this study by demonstrating that c-Myc induces transcription of a panel of ABC drug transporter genes. ABCs are a large family trans-membrane transporter deeply involved in multi drug resistance. Furthermore expression levels of Myc, ABCC1, ABCC4 and ABCF1 were proved to be important prognostic tool to predict conventional therapy failure. N-Myc amplification/overexpression is the most important prognostic factor for Neuroblastoma. Cyclin G2 and Clusterin are two genes often down regulated in neuroblastoma cells. Cyclin G2 is an atypical member of Cyclin family and its expression is associated with terminal differentiation and apoptosis. Moreover it blocks cell cycle progression and induces cell growth arrest. Instead, CLU is a multifunctional protein involved in many physiological and pathological processes. Several lines of evidences support the view that CLU may act as a tumour suppressor in Neuroblastoma. In this thesis I showed that N-Myc represses CCNG2 and CLU transcription by different mechanisms. • N-Myc represses CCNG2 transcription by directly interacting with Sp1 bound in CCNG2 promoter and recruiting HDAC2. Importantly, reactivation of CCNG2 expression through epigenetic drugs partially reduces N-Myc and HDAC2 mediated cell proliferation. • N-Myc/Max complex represses CLU expression by direct binding to a peculiar E-box element on CLU promoter and by recruitment of HDACs and Polycomb Complexes, to the CLU promoter. Overall our findings strongly support the model in which Myc overexpression/amplification may contribute to some aspects of oncogenesis by a dual action: i) transcription activation of genes that confer a multidrug resistant phenotype to cancer cells; ii), transcription repression of genes involved in cell cycle inhibition and cellular differentiation.

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Im Rahmen der Projekte CARIBIC ('Civil Aircraft for the Regular Investigation of the atmosphere Based on an Instrument Container') und INDOEX ('Indian Ocean Experi-ment') wurde ein Gaschromatograph mit Massenspektrometer zur Analyse von Luftproben auf Nicht-Methan-Kohlenwasserstoffe (NMKW) im ppb- und ppt-Bereich entwickelt. Während INDOEX erfolgte die Probennahme auf dem Forschungsschiff Ronald Brown, während CARIBIC mit einem automatischen Probensammler an Bord eines Passagierflugzeuges (Boeing 767-ER, LTU). Die NMKW-Meßergebnisse wurden zusammen mit Ergebnissen von Mes-sungen von Kohlenmonoxid (CO, einschließlich Isotopenzusam-mensetzung), Ozon (O3), Methan (CH4), Kohlendioxid (CO2), Distickstoffmonoxid (N2O), Schwefelhexafluorid (SF6) und Aerosoleigenschaften sowie meteorologischen Daten inter-pretiert. Während INDOEX (Februar / März 1999) wurde in der maritimen Grenzschicht (MBL) des Indischen Ozeans (IO) eine starke Variabilität diverser Spurengase beobachtet, die teilweise durch regionale Emissionen hervorgerufen wurde, die stärkste Variabilität war jedoch durch Langstrecken-transport aus mittleren Breiten der Nordhemisphäre bedingt. Aufgrund der Abweichungen vom klimatologischen Mittel, sollten regionale Quellen die MBL des IO im allgemeinen stärker beeinflussen. Die Einteilung des IO in meteorologi-sche Luftmassenregime wurde bestätigt. Starke Spurengasgra-dienten an der innertropischen Konvergenzzone (ITCZ) zeigen, daß die ITCZ in erster Linie den Austausch von Luftmassen zwischen den Hemisphären behindert. Bei CARIBIC werden Messungen von Spurengasen (ein-(schließlich NMKW) und Aerosoleigenschaften auf Flügen in der oberen Troposphäre / unteren Stratosphäre durchgeführt. Während eines Flug über Afrika wurden der Einfluß von durch Konvektion in die obere Troposphäre eingebrachten, frischen Abgasen aus Biomassenverbrennung nachgewiesen. Andere Luft-massen wurden durch Emissionen von Erdgas bzw. durch die Stratosphäre beeinflußt.