12 resultados para and biological systems with sources of variability

em Helda - Digital Repository of University of Helsinki


Relevância:

100.00% 100.00%

Publicador:

Resumo:

The new paradigm of connectedness and empowerment brought by the interactivity feature of the Web 2.0 has been challenging the traditional centralized performance of mainstream media. The corporation has been able to survive the strong winds by transforming itself into a global multimedia business network embedded in the network society. By establishing networks, e.g. networks of production and distribution, the global multimedia business network has been able to sight potential solutions by opening the doors to innovation in a decentralized and flexible manner. Under this emerging context of re-organization, traditional practices like sourcing need to be re- explained and that is precisely what this thesis attempts to tackle. Based on ICT and on the network society, the study seeks to explain within the Finnish context the particular case of Helsingin Sanomat (HS) and its relations with the youth news agency, Youth Voice Editorial Board (NÄT). In that sense, the study can be regarded as an explanatory embedded single case study, where HS is the principal unit of analysis and NÄT its embedded unit of analysis. The thesis was able to reach explanations through interrelated steps. First, it determined the role of ICT in HS’s sourcing practices. Then it mapped an overview of the HS’s sourcing relations and provided a context in which NÄT was located. And finally, it established conceptualized institutional relational data between HS and NÄT for their posterior measurement through social network analysis. The data set was collected via qualitative interviews addressed to online and offline editors of HS as well as interviews addressed to NÄT’s personnel. The study concluded that ICT’s interactivity and User Generated Content (UGC) are not sourcing tools as such but mechanism used by HS for getting ideas that could turn into potential news stories. However, when it comes to visual communication, some exemptions were found. The lack of official sources amidst the immediacy leads HS to rely on ICT’s interaction and UGC. More than meets the eye, ICT’s input into the sourcing practice may be more noticeable if the interaction and UGC is well organized and coordinated into proper and innovative networks of alternative content collaboration. Currently, HS performs this sourcing practice via two projects that differ, precisely, by the mode they are coordinated. The first project found, Omakaupunki, is coordinated internally by Sanoma Group’s owned media houses HS, Vartti and Metro. The second project found is coordinated externally. The external alternative sourcing network, as it was labeled, consists of three actors, namely HS, NÄT (professionals in charge) and the youth. This network is a balanced and complete triad in which the actors connect themselves in relations of feedback, recognition, creativity and filtering. However, as innovation is approached very reluctantly, this content collaboration is a laboratory of experiments; a ‘COLLABORATORY’.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

The purpose of this thesis is to examine Somalis who live in Finland through their memories. These memories are interpreted as subjective experiences emphasizing the significance of the past and religion in these memories. On the other hand, these memories are understood as a part of collective social memory of Somalis. This study also constructs a comparative perspective for practising Islam in Somalia and Finland. The methodological framework is based on theories of social memory, oral history and narrative analysis. The empirical data is collected by interviewing Somalis living in Finland. The interviews were conducted by using the method of half-structured thematic interview. The data consists of seven interviews. The interviewees are in the focus of this study since their experiences are considered as the main sources of information for this study. The empirical data of the study reveals that Somalis have maintained strong relations to Somalia. The relationship to Somalia is mainly constructed on positive memories. Memories from Somalia have acquired a significant role in the lives of the interviewees. Those memories will define their relation to both past and the present. In the context of religious memories, Islam is described as a way of living which provides advice and defines the terms of everyday life. As a part of those religious memories, the transmitting of Islamic and Somali values plays a significant role in the lives of Somalis in Finland. In such transmitting process of the values, the social religious memory has acquired a significant role. In the context of Islam in Finland, the religious education of children is mentioned as one of the most important features of the Islamic faith by the interviewees. In general, the practice of Islam does not create any major problems for the interviewees in Finland. The interviewees describe their practice of Islam quite similar when compared to their religious life in Somalia. The empirical data also points out the fact that the meaning of Islam has not changed after moving to Finland. Keywords: Somalis, Somalia, Islam, oral history, narrative research

Relevância:

100.00% 100.00%

Publicador:

Resumo:

The Baltic Sea was studied with respect to selected organic contaminants and their ecotoxicology. The research consisted of analyses of total hydrocarbons, polycyclic aromatic hydrocarbons, bile metabolites, hepatic ethoxyresorufin-O-deethylase (EROD) activity, polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs). The contaminants were measured from various matrices, such as seawater, sediment and biota. The methods of analysis were evaluated and refined to comparability of the results. Polyaromatic hydrocarbons, originating from petroleum, are known to be among the most harmful substances to the marine environment. In Baltic subsurface water, seasonal dependence of the total hydrocarbon concentrations (THCs) was seen. Although concentrations of parent polycyclic aromatic hydrocarbons (PAHs) in sediment surface varied between 64 and 5161 ug kg-1 (dw), concentrations above 860 ug kg-1 (dw) were found in all the studied sub-basins of the Baltic Sea. Concentrations commonly considered to substantially increase the risk of liver disease and reproductive impairment in fish, as well as potential effects on growth (above 1000 ug kg-1 dw), were found in all the studied sub-basins of the Baltic Sea except Kattegat. Thus, considerable pollution in sediments was indicated. In bivalves, the sums of 12 PAHs varied on a wet weight basis between 44 and 298 ug kg-1 (ww). The predominant PAHs were high molecular weight and the PAH profiles of M. balthica differed from those found in sediment from the same area. The PAHs were both pyrolytic and petrogenic in origin, and a contribution from diesel engines was found, which indicates pollution of the Baltic Sea, most likely caused by the steadily increasing shipping in the area. The HPLC methods developed for hepatic EROD activity and bile metabolite measurements proved to be fast and suitable for the study of biological effects. A mixed function oxygenase enzyme system in Baltic Sea perch collected from the Gulf of Finland was induced slightly: EROD activity in perch varied from 0.30 14 pmol min-1 mg-1 protein. This range can be considered to be comparable to background values. Recent PAH exposure was also indicated by enhanced levels (213 and 1149 ug kg-1) of the bile metabolite 1-hydroxypyrene. No correlation was indicated between hepatic EROD activity and concentration of 1-hydroxypyrene in bile. PCBs and OCPs were observed in Baltic Sea sediment, bivalves and herring. Sums of seven CBs in surface sediment (0 5 cm) ranged from 0.04 to 6.2 ug kg-1 (dw) and sums of three DDTs from 0.13 to 5.0 ug kg-1 (dw). The highest levels of contaminants were found in the most eastern area of the Gulf of Finland where the highest total carbon and nitrogen content was found and where the lowest percentage proportion of p,p -DDT was found. The highest concentrations of CBs and the lowest concentration of DDTs were found in M. balthica from the Gulf of Finland. The highest levels of DDTs were found in M. balthica from the Hanö Bight, which is the outer part of the Bornholm Basin close to the Swedish mainland. In bivalves, the sums of seven CBs were 72 108 ug kg-1 (lw) and the sums of three DDTs were 66 139 ug kg-1 (lw). Results from temporal trend monitoring showed, that during the period 1985 2002, the concentrations of seven CBs in two-year-old female Baltic herring were clearly decreased, from 9 16 to 2 6 ug kg-1 (ww) in the northern Baltic Sea. At the same time, concentrations of three DDTs declined from 8 15 to 1 5 ug kg-1 (ww). The total concentration of the fat-soluble CBs and DDTs in Baltic herring muscle was shown to be age-dependent; the average concentrations in ten-year-old Baltic herring were three to five-fold higher than in two-year-old herring. In Baltic herring and bivalves, as well as in surface sediments, CB 138 and CB153 were predominant among CBs, whereas among DDTs p,p'-DDD predominated in sediment and p,p'-DDE in bivalves and Baltic herring muscle. Baltic Sea sediments are potential sources of contaminants that may become available for bioaccumulation. Based on ecotoxicological assessment criteria, cause for concern regarding CBs in sediments was indicated for the Gulf of Finland and the northern Baltic Proper, and for the northern Baltic Sea regarding CBs in Baltic herring more than two years old. Statistical classification of selected organic contaminants indicated high-level contamination for p,p'-DDT, p,p'-DDD, p,p'-DDE, total DDTs, HCB, CB118 and CB153 in muscle of Baltic herring in age groups two to ten years; in contrast, concentrations of a-HCH and g-HCH were found to be moderate. The concentrations of DDTs and CBs in bivalves is sufficient to cause biological effects, and demonstrates that long-term biological effects are still possible in the case of DDTs in the Hanö Bight.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Breast cancer is the most common cancer in women in Western countries. In the early stages of development most breast cancers are hormone-dependent, and estrogens, especially estradiol, have a pivotal role in their development and progression. One approach to the treatment of hormone-dependent breast cancers is to block the formation of the active estrogens by inhibiting the action of the steroid metabolising enzymes. 17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is a key enzyme in the biosynthesis of estradiol, the most potent female sex hormone. The 17beta-HSD1 enzyme catalyses the final step and converts estrone into the biologically active estradiol. Blocking 17beta-HSD1 activity with a specific enzyme inhibitor could provide a means to reduce circulating and tumour estradiol levels and thus promote tumour regression. In recent years 17beta-HSD1 has been recognised as an important drug target. Some inhibitors of 17beta-HSD1 have been reported, however, there are no inhibitors on the market nor have clinical trials been announced. The majority of known 17beta-HSD1 inhibitors are based on steroidal structures, while relatively little has been reported on non-steroidal inhibitors. As compared with 17beta-HSD1 inhibitors based on steroidal structures, non-steroidal compounds could have advantages of synthetic accessibility, drug-likeness, selectivity and non-estrogenicity. This study describes the synthesis of large group of novel 17beta-HSD1 inhibitors based on a non-steroidal thieno[2,3-d]pyrimidin-4(3H)-one core. An efficient synthesis route was developed for the lead compound and subsequently employed in the synthesis of thieno[2,3-d]pyrimidin-4(3H)-one based molecule library. The biological activities and binding of these inhibitors to 17beta-HSD1 and, finally, the quantitative structure activity relationship (QSAR) model are also reported. In this study, several potent and selective 17beta-HSD1 inhibitors without estrogenic activity were identified. This establishment of a novel class of inhibitors is a progressive achievement in 17beta-HSD1 inhibitor development. Furthermore, the 3D-QSAR model, constructed on the basis of this study, offers a powerful tool for future 17beta-HSD1 inhibitor development. As part of the fundamental science underpinning this research, the chemical reactivity of fused (di)cycloalkeno thieno[2,3-d]pyrimidin-4(3H)-ones with electrophilic reagents, i.e. Vilsmeier reagent and dimethylformamide dimethylacetal, was investigated. These findings resulted in a revision of the reaction mechanism of Vilsmeier haloformylation and further contributed to understanding the chemical reactivity of this compound class. This study revealed that the reactivity is dependent upon a stereoelectronic effect arising from different ring conformations.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Ectomycorrhizal formation between the host tree, Pinus sylvestris and fungal symbiont, Suillus bovinus was investigated at the molecular level by isolating genes regulating the organization of the actin cytoskeleton in the fungal partner S. bovinus. An Agrobacterium tumefaciens mediated transformation (ATMT) system was developed for the ectomycorrhizal fungi in order to assign specific functions to the cloned molecules. The developed ATMT system was also used to transform a plant pathogenic fungus, Helminthosporium turcicum, to hygromycin B resistance. Small GTPases Cdc42 and Rac1, the regulators of actin cytoskeleton in eukaryotes were isolated from S. bovinus. Sbcdc42 and Sbrac1, are both expressed in vegetative and in the symbiotic hyphae of S. bovinus . Using IIF microscopy, Cdc42 and actin were co-localized at the tips of vegetative hyphae and were visualized in association with the plasma membrane in swollen cells typical to the symbiotic hyphae. These results suggest that the small GTPases Cdc42 may play a significant role in the polarized growth of S. bovinus hyphae and regulate fungal morphogenesis during ectomycorrhiza formation through reorganization of the actin cytoskeleton. The functional equality of Cdc42 was tested in yeast complementation experiments using a Saccharomyces cerevisiae temperature sensitive mutant, cdc42-1ts. The genomic clone of CDC42 was isolated from S. bovinus genomic DNA via specific primers for Cdc42. The analogous S. cerevisiae cdc42 mutations, dominant active G12V and dominant negative D118A, were generated in the Sbcdc42 gene by in-vitro mutagenesis. The ectomycorrhizal fungi, S. bovinus, P. involutus and H. cylindroporum were transformed using ATMT and phleomycin as a selectable marker. PCR screeing suggested that the T-DNA was inserted in all the three fungal genomes but the fate of integration could not be proved by Southern blot analysis. An alternative Agrobacterium strain, AGL-1 and selection marker, hygromycin was used to transform our model fungus S. bovinus. PCR and Southern analysis suggested an improved efficiency of transformation. All the transformed fungal colonies selected for hygromycin gave positives in PCR and the Southerns showed multiple or single copy T-DNA integrations into the S. bovinus genome. Using the same Agrobacterium strain and the selectable marker, a maize pathogen, H. turcicum was also subjected to ATMT. The H. turcicum transformation data suggested the single copy T-DNA integrations into the genome of the screened transformants that further confirms wider applicability of the ATMT. The plasmids carrying the wild-type (pHGCDC42) and the mutated Sbcdc42 alleles (pHGGV; pHGDA) under Agaricus bisporus gpd promoter were constructed in an A. tumefaciens vector. ATMT was used to transform S. bovinus with the plasmids carrying the wild-type and mutated Sbcdc42 alleles. The isolation of Sbcdc42 and Sbrac1 genes and some other functionally related genes from ectomycorrhizal fungus, S. bovinus will form the basis of future work to resolve the signalling pathway leading to ectomycorrhizal symbiosis. The development of ATMT system will be a valuable tool in analysing the exact function of signalling pathway components in ectomycorrhizal symbiosis or in plant pathogenic interactions. The transformation frequency and broad applicability along with the simplicity of T-DNA integration make Agrobacterium a valuable, new and a powerfull tool for targeted and insertional mutagenesis in these plant associated fungi. The developed ATMT systems should therefore make it possible to generate large number of transformants with tagged genes which could then be screened for their specific roles in symbiosis and pathogenecity, respectively.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

In Africa various species of Combretum, Terminalia and Pteleopsis are used in traditional medicine. Despite of this, some species of these genera have still not been studied for their biological effects to validate their traditional uses. The aim of this work has been to document the ethnomedicinal uses of several species of Combretum and Terminalia in Mbeya region, south-western Tanzania, and to use this information for finding species with good antimicrobial and cytotoxic potential. During a five weeks expedition to Tanzania in spring 1999 sixteen different species of Combretum and Terminalia, as well as Pteleopsis myrtifolia were collected from various locations in the districts of Mbeya, Iringa and Dar-es-Salaam. Traditional healers in seven different villages in the Mbeya region were interviewed in Swahili and Nyakyusa on the medicinal uses of Combretum and Terminalia species shown to them. A questionnaire was used during the interviews. The results of the interviews correlated well between different villages, the same species being used in similar ways in different villages. Of the ten species shown to the healers six were frequently used for treatment of skin diseases, bacterial infections, diarrhea, oedema and wounds. The dried plants were most commonly prepared into hot water decoctions or mixed into maize porridge, Ugali. Infusions made from dried or fresh plant material were also common. Wounds and topical infections were treated with ointments made from the dried plant material mixed with sheep fat. Twenty-one extracts of six species of Combretum and four of Terminalia, collected from Tanzania, were screened for their antibacterial effects against two gram-negative and five gram-positive bacteria, as well as the yeast, Candida albicans, using an agar diffusion method. Most of the screened plants showed substantial antimicrobial activity. A methanolic root extract of T. sambesiaca showed the most potent antibacterial effects of all the plant species screened, and gave a MIC value of 0.9 mg/ml against Enterobacter aerogenes. Also root extracts of T. sericea and T. kaiserana gave excellent antimicrobial effects, and notably a hot water extract of T. sericea was as potent as extracts of this species made from EtOH and MeOH. Thus, the traditional way of preparing T. sericea into hot water decoctions seems to extract antimicrobial compounds. Thirty-five extracts of five species of Terminalia, ten of Combretum and Pteleopsis myrtifolia were screened for their antifungal effects against five species of yeast (Candida spp.) and Cryptococcus neoformans. The species differed from each other to their antifungal effects, some being very effective whereas others showed no antifungal effects. The most effective extracts showed antifungal effects comparable to the standard antibiotics itraconazol and amphotericin B. Species of Terminalia gave in general stronger antifungal effects than those of Combretum. The best effects were obtained with methanolic root extracts of T. sambesiaca, T. sericea and T. kaiserana, and this investigation indicates that decoctions of these species might be used for treatment of HIV-related fungal infections. Twenty-seven crude extracts of eight species of Combretum, five of Terminalia and Pteleopsis myrtifolia were evaluated for their cytotoxic effects against human cancer cell lines (HeLa, cervical carcinoma; MCF 7, breast carcinoma, T 24 bladder carcinoma) and one endothelial cell line (BBCE, bovine brain capillary endothelial cells). The most outstanding effects were obtained with a leaf extract of Combretum fragrans, which nearly totally inhibited the proliferation of T 24 and HeLa cells at a concentration of 25 ug/ml and inhibited 60 % of the growth of the HeLa cells at a concentration of 4.3 ug/ml. The species of Terminalia were less cytotoxically potent than the Combretum species, although T. sericea and T. sambesiaca gave good cytotoxic effects (< 30 % proliferation). In summary this study indicates that some of the species of Terminalia, Combretum and Pteleopsis, used in Tanzanian traditional medicine, are powerful inhibitors of both microbial and cancer cell growth. In depth studies would be needed to find the active compounds behind these biological activities.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Background: Alcohol consumption and smoking are the main causes of upper digestive tract cancers. These risk factors account for over 75% of all cases in developed countries. Epidemiological studies have shown that alcohol and tobacco interact in a multiplicative way to the cancer risk, but the pathogenetic mechanism behind this is poorly understood. Strong experimental and human genetic linkage data suggest that acetaldehyde is one of the major factors behind the carcinogenic effect. In the digestive tract, acetaldehyde is mainly formed by microbial metabolism of ethanol. Acetaldehyde is also a major constituent of tobacco smoke. Thus, acetaldehyde from both of these sources may have an interacting carcinogenic effect in the human upper digestive tract. Aims: The first aim of this thesis was to investigate acetaldehyde production and exposure in the human mouth resulting from alcohol ingestion and tobacco smoking in vivo. Secondly, specific L-cysteine products were prepared to examine their efficacy in the binding of salivary acetaldehyde in order to reduce the exposure of the upper digestive tract to acetaldehyde. Methods: Acetaldehyde levels in saliva were measured from human volunteers during alcohol metabolism, during tobacco smoking and during the combined use of alcohol and tobacco. The ability of L-cysteine to eliminate acetaldehyde during alcohol metabolism and tobacco smoking was also investigated with specifically developed tablets. Also the acetaldehyde production of Escherichia coli - an important member of the human microbiota - was measured in different conditions prevailing in the digestive tract. Results and conclusions: These studies established that smokers have significantly increased acetaldehyde exposure during ethanol consumption even when not actively smoking. Acetaldehyde exposure was dramatically further increased during active tobacco smoking. Thus, the elevated aerodigestive tract cancer risk observed in smokers and drinkers may be the result of the increased acetaldehyde exposure. Acetaldehyde produced in the oral cavity during ethanol challenge was significantly decreased by a buccal L-cysteine -releasing tablet. Also smoking-derived acetaldehyde could be totally removed by using a tablet containing L-cysteine. In conclusion, this thesis confirms the essential role of acetaldehyde in the pathogenesis of alcohol- and smoking-induced cancers. This thesis presents a novel experimental approach to decrease the local acetaldehyde exposure of the upper digestive tract with L-cysteine, with the eventual goal of reducting the prevalence of upper digestive tract cancers.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

The goals of this study were to analyze the forms of emotional tendencies that are likely to motivate moral behaviors, and to find correlates for these tendencies. In study 1, students narratives of their own guilt or shame experiences were analyzed. The results showed that pure shame was more likely to motivate avoidance than reparation, whereas guilt and combination of guilt and shame were likely to motivate reparation. However, all types of emotion could lead to chronic rumination if the person was not clearly responsible for the situation. In study 2, the relations of empathy with two measures of guilt were examined in a sample of 13- to 16-year-olds (N=113). Empathy was measured using Davis s IRI and guilt by Tangney s TOSCA and Hoffman s semi-projective story completion method that includes two different scenarios, guilt over cheating and guilt over inaction. Empathy correlated more strongly with both measures of guilt than the two measures correlated with each other. Hoffman s guilt over inaction was more strongly associated with empathy measures in girls than in boys, whereas for guilt over cheating the pattern was the opposite. Girls and boys who describe themselves as empathetic may emphasize different aspect of morality and feel guilty in different contexts. In study 3, cultural and gender differences in guilt and shame (TOSCA) and value priorities (the Schwartz Value Survey) were studied in samples of Finnish (N=156) and Peruvian (N=159) adolescents. Gender differences were found to be larger and more stereotypical among the Finns than among the Peruvians. Finnish girls were more prone to guilt and shame than boys were, whereas among the Peruvians there was no gender difference in guilt, and boys were more shame-prone than girls. The results support the view that psychological gender differences are largest individualistic societies. In study 4, the relations of value priorities to guilt, shame and empathy were examined in two samples, one of 15 19-year-old high school students (N = 207), and the other of military conscripts (N = 503). Guilt was, in both samples, positively related to valuing universalism, benevolence, tradition, and conformity, and negatively related to valuing power, hedonism, stimulation, and self-direction. The results for empathy were similar, but the relation to the openness conservation value dimension was weaker. Shame and personal distress were weakly related to values. In sum, shame without guilt and the TOSCA shame scale are tendencies that are unlikely to motivate moral behavior in Finnish cultural context. Guilt is likely to be connected to positive social behaviors, but excessive guilt can cause psychological problems. Moral emotional tendencies are related to culture, cultural conceptions of gender and to individual value priorities.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Ewing sarcoma is an aggressive and poorly differentiated malignancy of bone and soft tissue. It primarily affects children, adolescents, and young adults, with a slight male predominance. It is characterized by a translocation between chromosomes 11 and 22 resulting in the EWSR1-FLI1fusion transcription factor. The aim of this study is to identify putative Ewing sarcoma target genes through an integrative analysis of three microarray data sets. Array comparative genomic hybridization is used to measure changes in DNA copy number, and analyzed to detect common chromosomal aberrations. mRNA and miRNA microarrays are used to measure expression of protein-coding and miRNA genes, and these results integrated with the copy number data. Chromosomal aberrations typically contain also bystanders in addition to the driving tumor suppressor and oncogenes, and integration with expression helps to identify the true targets. Correlation between expression of miRNAs and their predicted target mRNAs is also evaluated to assess the results of post-transcriptional miRNA regulation on mRNA levels. The highest frequencies of copy number gains were identified in chromosome 8, 1q, and X. Losses were most frequent in 9p21.3, which also showed an enrichment of copy number breakpoints relative to the rest of the genome. Copy number losses in 9p21.3 were found have a statistically significant effect on the expression of MTAP, but not on CDKN2A, which is a known tumor-suppressor in the same locus. MTAP was also down-regulated in the Ewing sarcoma cell lines compared to mesenchymal stem cells. Genes exhibiting elevated expression in association with copy number gains and up-regulation compared to the reference samples included DCAF7, ENO2, MTCP1, andSTK40. Differentially expressed miRNAs were detected by comparing Ewing sarcoma cell lines against mesenchymal stem cells. 21 up-regulated and 32 down-regulated miRNAs were identified, includingmiR-145, which has been previously linked to Ewing sarcoma. The EWSR1-FLI1 fusion gene represses miR-145, which in turn targets FLI1 forming a mutually repressive feedback loop. In addition higher expression linked to copy number gains and compared to mesenchymal stem cells, STK40 was also found to be a target of four different miRNAs that were all down-regulated in Ewing sarcoma cell lines compared to the reference samples. SLCO5A1 was identified as the only up-regulated gene within a frequently gained region in chromosome 8. This region was gained in over 90 % of the cell lines, and also with a higher frequency than the neighboring regions. In addition, SLCO5A1 was found to be a target of three miRNAs that were down-regulated compared to the mesenchymal stem cells.