82 resultados para Special resistance

em Helda - Digital Repository of University of Helsinki


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The range of consumer health and medicines information sources has diversified along with the increased use of the Internet. This has led to a drive to develop medicines information services and to better incorporate the Internet and e-mail into routine practice in health care and in community pharmacies. To support the development of such services more information is needed about the use of online information by consumers, particularly of those who may be the most likely to use and to benefit from the new sources and modes of medicines communication. This study explored the role and utilization of the Internet-based medicines information and information services in the context of a wider network of information sources accessible to the public in Finland. The overall aim was to gather information to develop better and more accessible sources of information for consumers and services to better meet the needs of consumers. Special focus was on the needs and information behavior among people with depression and using antidepressant medicines. This study applied both qualitative and quantitative methods. Consumer medicines information needs and sources were identified by analyzing the utilization of the University Pharmacy operated national drug information call center (Study I) and surveying Finnish adults (n=2348) use of the different medicines information sources (Study II). The utilization of the Internet as a source of antidepressant information among people with depression was explored by focus group discussions among people with depression and with current or past use of the antidepressant(s) (n=29, Studies III & IV). Pharmacy response to the needs of consumers in term of providing e-mail counseling was assessed by conducting a virtual pseudo customer study among the Finnish community pharmacies (n=161, Study V). Physicians and pharmacists were the primary sources of medicines information. People with mental disorders were more frequent users of telephone- and Internet-based medicines information sources and patient information leaflets than people without mental disorders. These sources were used to complement rather than replace information provided face-to-face by health professionals. People with depression used the Internet to seek facts about antidepressants, to share experiences with peers, and for the curiosity. They described that the access to online drug information was empowering. Some people reported lacking the skills necessary to assess the quality of online information. E-mail medication counseling services provided by community pharmacies were rare and varied in quality. Study results suggest that rather than discouraging the use of the Internet, health professionals should direct patients to use accurate and reliable sources of online medicines information. Health care providers, including community pharmacies should also seek to develop new ways of communicating information about medicines with consumers. This study determined that people with depression and using antidepressants need services enabling interactive communication not only with health care professionals, but also with peers. Further research should be focused on developing medicines information service facilitating communication among different patient and consumer groups.

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Finnish scholarship students in Russia during the autonomy (1812-1917) During the autonomy in Finland (1809-1917), an attempt to improve the knowledge of the Russian language was made through special language university scholarships. With these scholarships the students could go and study the Russian language and acquire cultural knowledge in Russia. Other member countries on the edges of the Russian Empire, like Poland and the Baltic provinces, did not have similar programs. The first two scholars started their journey in 1812. A system of travel allowances was introduced in 1841. Between the years 1812- 1917 a total of almost 400 students studied in Russia. The studies mainly took place in Moscow. These scholarship students were called the Master s of Moscow ". In this paper, Finnish-Russian relations are studied based on the attitude towards the Russian language and the people who studied it in Finland. Although the attitude towards them was neutral in the beginning, in 1844 there was a strong change. Students of Russian, and especially the scholars, received the stigma of being unreliable and unpatriotic, a stigma they were never able to get rid of. The study of the Russian language was voluntary in Finnish schools between 1863 and 1872. Starting from 1890, however, the study of the Russian language was enforced. In doing so, the Russians attempted to unify the Empire, while the Finns had the illusion that they had their own state. Thus, Russia saw the language as a way to unify the Empire and Finns as an attempt to make them Russians. The purpose of studying in Russia was to improve the student s practical language skills and overall knowledge of the customs and culture of the country. Besides knowing the language, knowledge of Russian culture and customs is essential in understanding Russia and Russians; therefore, the studies of literature, geography and history have been noted in this research. Without knowledge it is difficult to develop understanding. After their studies, almost all of the scholars returned to Finland and did not continue their careers in Russia. They worked mainly as teachers and civil servants, and managed to improve the Finnish people s weak knowledge of Russian and Russia through teaching, translations of literature and newspaper articles. Through these scholars, it is possible to see how the attitudes towards the language have been closely related to the political history between Finland and Russia. The language became the subject of resistance and these attitudes were transferred to its students. In 1917, the study of Russia and the Russian language ended and it was no longer possible to use the acquired knowledge of language and country in independent Finland.

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The methodology of designing normative terminological products has been described in several guides and international standards. However, this methodology is not always applicable to designing translation-oriented terminological products which differ greatly from normative ones in terms of volume, function, and primary target group. This dissertation has three main goals. The first is to revise and enrich the stock of concepts and terms required in the process of designing an LSP dictionary for translators. The second is to detect, classify, and describe the factors which determine the characteristics of an LSP dictionary for translators and affect the process of its compilation. The third goal is to provide recommendations on different aspects of dictionary design. The study is based on an analysis of dictionaries, dictionary reviews, literature on translation-oriented lexicography, material from several dictionary projects, and the results of questionnaires. Thorough analysis of the concept of a dictionary helped us to compile a list of designable characteristics of a dictionary. These characteristics include target group, function, links to other resources, data carrier, list of lemmata, information about the lemmata, composition of other parts of the dictionary, compression of the data, structure of the data, and access structure. The factors which determine the characteristics of a dictionary have been divided into those derived from the needs of the intended users and those reflecting the restrictions of the real world (e.g. characteristics of the data carrier and organizational factors) and attitudes (e.g. traditions and scientific paradigms). The designer of a dictionary is recommended to take the intended users' needs as the starting point and aim at finding the best compromise between the conflicting factors. When designing an LSP dictionary, much depends on the level of knowledge of the intended users about the domain in question as well as their general linguistic competence, LSP competence, and lexicographic competence. This dissertation discusses the needs of LSP translators and the role of the dictionary in the process of translation of an LSP text. It also emphasizes the importance of planning lexicographic products and activities, and addresses many practical aspects of dictionary design.

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My dissertation is a corpus-based study of non-finite constructions in Old English (OE). It revisits the question of Latin influence on the OE syntax, offering a new evaluation of syntactic interference between Latin and OE, and, more generally, of the contact situation in the OE period, drawing on methods used in studying grammaticalization and language contact. I address three non-finite constructions: absolute participial construction, accusative-and-infinitive construction, and nominative-and-infinitive construction, exemplified respectively in present-day English as - She looked like a pixie sometimes, her eyes darting here and there, forever watchful (BNC CCM 98); - My first acquaintance with her was when I heard her sing (BNC CFY 2215); - Charles the Bald was said to resemble his grandfather physically (BNC HPT 175). This study compares data from translated texts against the background of original OE writings, establishing dependencies and differences between the two. Although the contrastive analysis of source and target texts is one of the major methods employed in the study, translation and translation strategies as such are only my secondary foci. The emphasis is rather on what source/target comparison can tell us about the OE non-finite syntax and the typological differences between Latin and OE in this domain, and on whether contact-induced change can originate in translation. In terms of theoretical framework, I have adopted functional-typological approach, which rests on the principles of iconicity and event integration, and to the best of my knowledge, has not been applied systematically to OE non-finite constructions. Therefore one more aim of the dissertation is to test this framework and to see how OE fits into the cross-linguistic picture of non-finites. My research corpus consists of two samples: 1) written OE closely dependent on the Latin originals, based on editions of two gloss texts, five translations, and Latin originals of these texts, representing four text types: hymns, religious regulations, homily/life narrative, and biblical narrative (180,622 words); and 2) written OE as far independent from Latin as possible, based on a selection from the York-Toronto-Helsinki Parsed Corpus of Old English Prose (YCOE) and representing five text types: laws, charters, correspondence, chronicle narrative, and homily/life narrative (274,757 words).

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Titled "An Essay on Antimetaphoric Resistance", the dissertation investigates what is here being called "Counter-figures": a term which has in this context a certain variety of applications. Any other-than-image or other-than-figure, anything that cannot be exhausted by figuration (and that is, more or less, anything at all, except perhaps the reproducible images and figures themselves) can be considered "counter-figurative" with regard to the formation of images and figures, ideas and schemas, "any graven image, or any likeness of any thing". Singularity and radical alterity, as well as temporality and its peculiar mode of uniqueness are key issues here, and an ethical dimension is implied by, or intertwined with, the aesthetic. In terms borrowed from Paul Celan's "Meridian" speech, poetry may "allow the most idiosyncratic quality of the Other, its time, to participate in the dialogue". This connection between singularity, alterity and temporality is one of the reasons why Celan so strongly objects to the application of the traditional concept of metaphor to poetry. As Celan says, "carrying over [übertragen]" by metaphor may imply an unwillingness to "bear with [mittragen]" and to "endure [ertragen]" the poem. The thesis is divided into two main parts. The first consists of five distinct prolegomena which all address the mentioned variety of applications of the term "counter-figures", and especially the rejection or critique of either metaphor (by Aristotle, for instance) or the concept of metaphor (defined by Aristotle, and sometimes deemed "anti-poetic" by both theorists and poets). Even if we restrict ourselves to the traditional rhetorico-poetical terms, we may see how, for instance, metonymy can be a counter-figure for metaphor, allegory for symbol, and irony for any single trope or for any piece of discourse at all. The limits of figurality may indeed be located at these points of intersection between different types of tropes or figures, and even between figures or tropes and the "non-figurative trope" or "pseudo-figure" called catachresis. The second part, following on from the open-ended prolegomena, concentrates on Paul Celan's poetry and poetics. According to Celan, true poetry is "essentially anti-metaphoric". I argue that inasmuch as we are willing to pay attention to the "will" of the poetic images themselves (the tropes and metaphors in a poem) to be "carried ad absurdum", as Celan invites us to do, we may find alternative ways of reading poetry and approaching its "secret of the encounter", precisely when the traditional rhetorical instruments, and especially the notion of metaphor, become inapplicable or suspicious — and even where they still seem to impose themselves.

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Increased consumption of low-fat milk products is inversely associated with the risk of hypertension. The beneficial effect of milk on blood pressure is attributed to high calcium and potassium content but also to specific peptide sequences, which are cleaved from milk protein during gastrointestinal digestion, fermentation of milk with proteolytic starter cultures or enzymatic hydrolysis. Milk products fermented with Lactobacillus helveticus contain casein-derived tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro), which have been shown to possess antihypertensive effects in humans and in experimental animals. The aim of the present series of studies was to investigate the effects of tripeptides Ile-Pro-Pro and Val-Pro-Pro or fermented milk products containing them on vascular function and blood pressure and to elucidate the mechanisms behind them by using different experimental models of hypertension. Another aim was to characterize the acute effects of tripeptides on blood pressure and arterial stiffness in mildly hypertensive humans. Ile-Pro-Pro and Val-Pro-Pro or fermented milk products containing them attenuated the development of hypertension in two experimental models of hypertension, spontaneously hypertensive rat (SHR) and type 2 diabetic Goto-Kakizaki (GK) rat fed with high-salt diet. Significant differences in systolic blood pressure (SBP) were seen after 8 weeks treatment with tripeptide-containing products compared to control product. Plant sterols did not enhance this effect. Two differently produced tripeptide powders produced a similar attenuating effect on SBP in SHR. In mildly hypertensive subjects, a single administration of tripeptide- and plant sterol-containing fermented milk product decreased both SBP and diastolic blood pressure (DBP) over a period of 8 hours. Protective effect of tripeptides Ile-Pro-Pro and Val-Pro-Pro and fermented milk products containing them on vascular function was demonstrated in in vitro studies and long-term experimental studies. The effect was shown to be endothelium-dependent and possibly involving endothelium-derived hyperpolarizing factor (EDHF). In the clinical study, single administration of tripeptide-containing fermented milk product did not affect measures of arterial stiffness. Long-term treatment with fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro inhibited angiotensin-converting enzyme (ACE) and decreased aldosterone levels thus showing beneficial effects on the renin-angiotensin system (RAS) in SHR and GK. No changes in the components of RAS were observed by the single administration of the same product in mildly hypertensive subjects. Increased levels of cGMP, NOx and citrulline suggest increased nitric oxide (NO) production by the tripeptides. Taken together, Ile-Pro-Pro and Val-Pro-Pro -containing products attenuate the development of hypertension after long-term treatment in experimental models of hypertension and possess an acute antihypertensive effect in mildly hypertensive subjects. In addition, these tripeptides show endothelium-mediated beneficial effects on vascular function. Attenuation of blood pressure increase by the tripeptides in experimental animals involves RAS, but its role in the antihypertensive effect in humans remains to be elucidated.

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Regardless of the existence of antibiotics, infectious diseases are the leading causes of death in the world. Staphylococci cause many infections of varying severity, although they can also exist peacefully in many parts of the human body. Most often Staphylococcus aureus colonises the nose, and that colonisation is considered to be a risk factor for spread of this bacterium. S. aureus is considered to be the most important Staphylococcus species. It poses a challenge to the field of medicine, and one of the most problematic aspects is the drastic increase of the methicillin-resistant S. aureus (MRSA) strains in hospitals and community world-wide, including Finland. In addition, most of the clinical coagulase-negative staphylococcus (CNS) isolates express resistance to methicillin. Methicillin-resistance in S. aureus is caused by the mecA gene that encodes an extra penicillin-binding protein (PBP) 2a. The mecA gene is found in a mobile genomic island called staphylococcal chromosome cassette mec (SCCmec). The SCCmec consists of the mec gene and cassette chromosome recombinase (ccr)gene complexes. The areas of the SCCmec element outside the ccr and mec complex are known as the junkyard J regions. So far, eight types of SCCmec(SCCmec I- SCCmec VIII) and a number of variants have been described. The SCCmec island is an acquired element in S. aureus. Lately, it appears that CNS might be the storage place of the SCCmec that aid the S. aureus by providing it with the resistant elements. The SCCmec is known to exist only in the staphylococci. The aim of the present study was to investigate the horizontal transfer of SCCmec between the S. aureus and CNS. One specific aim was to study whether or not some methicillin-sensitive S. aureus (MSSA) strains are more inclined to receive the SCCmec than others. This was done by comparing the genetic background of clinical MSSA isolates in the health care facilities of the Helsinki and Uusimaa Hospital District in 2001 to the representatives of the epidemic MRSA (EMRSA) genotypes, which have been encountered in Finland during 1992-2004. Majority of the clinical MSSA strains were related to the EMRSA strains. This finding suggests that horizontal transfer of SCCmec from unknown donor(s) to several MSSA background genotypes has occurred in Finland. The molecular characteristics of representative clinical methicillin-resistant S. epidermidis (MRSE) isolates recovered in Finnish hospitals between 1990 and 1998 were also studied, examining their genetic relation to each other and to the internationally recognised MRSE clones as well, so as to ascertain the common traits between the SCCmec elements in MRSE and MRSA. The clinical MRSE strains were genetically related to each other; eleven PFGE types were associated with sequence type ST2 that has been identified world-wide. A single MRSE strain may possess two SCCmec types III and IV, which were recognised among the MRSA strains. Moreover, six months after the onset of an outbreak of MRSA possessing a SCCmec type V in a long-term care facility in Northern Finland (LTCF) in 2003, the SCCmec element of nasally carried methicillin-resistant staphylococci was studied. Among the residents of a LTCF, nasal carriage of MR-CNS was common with extreme diversity of SCCmec types. MRSE was the most prevalent CNS species. Horizontal transfer of SCCmec elements is speculated to be based on the sharing of SCCmec type V between MRSA and MRSE in the same person. Additionally, the SCCmec element of the clinical human S. sciuri isolates was studied. Some of the SCCmec regions were present in S. sciuri and the pls gene was common in it. This finding supports the hypothesis of genetic exchange happening between staphylococcal species. Evaluation of the epidemiology of methicillin-resistant staphylococcal colonisation is necessary in order to understand the apparent emergence of these strains and to develop appropriate control strategies. SCCmec typing is essential for understanding the emergence of MRSA strains from CNS, considering that the MR-CNS may represent the gene pool for the continuous creation of new SCCmec types from which MRSA might originate.

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In complement activation, Factor H (FH) and C4b-binding protein (C4bp) are the key regulators that prevent the complement cascade from attacking host tissues. Some bacteria may bind and deposit these regulators on their own surfaces and thus provide themselves with an efficient means to avoid complement activation. In consequence, bacteria resist complement-mediated lysis and opsonin-dependent phagocytosis. This study has demonstrated that Y. enterocolitica, similar to many other pathogens, recruits both FH and C4bp to its surface to ensure protection against the complement-mediated killing. YadA and Ail, the most crucial serum resistance factors of Y.enterocolitica, mediate the binding of FH and C4bp. FH - YadA interaction involves multiple higher structural motifs on the YadA stalk and the short consensus repeats (SCRs) of the entire polypeptide chain of FH. The Ail binding site on FH has been located to SCRs 6 and 7. The binding site for FH on Ail, however, remains undetermined. Both YadA- and Ail-bound regulators display full cofactor activity for FI-mediated cleavage of C3b/C4b. FH/C4bp-binding characteristics do, however, differ between YadA and Ail. In addition, Ail captures the regulators only in the absence of blocking lipopolysaccharide O-antigen and outer core, whereas YadA binds FH/C4bp independent of the presence of other surface factors Independent of mode of binding, however, YadA and Ail provide Y. enterocolitica a means to avoid complement-mediated lysis, enhancing chances for the bacteria to survive in the host during various phases of infection.

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Rituximab, a monoclonal antibody against B-cell specific CD20 antigen, is used for the treatment of non-Hodgkin lymphomas (NHL) and chronic lymphatic leukemia. In combination with chemotherapeutics rituximab has remarkably improved the outcome of NHL patients, but a vast variation in the lengths of remissions remains and the outcome of individual patients is difficult to predict. This thesis has searched for an explanation for this by studying the effector mechanisms of rituximab and by comparing gene expression in lymphoma tissue samples of patients with long- and short-term survival. This work demonstrated that activation of complement (C) system is in vitro more efficient effector mechanism of rituximab than cellular mechanisms or apoptosis. Activation of the C system was also shown in vivo during rituximab treatment. However, intravenously administered rituximab could not enter the cerebrospinal fluid, and neither C activation nor removal of lymphoma cells was observed in central nervous system. In vitro cytotoxicity assays showed that rituximab-induced cell killing could be markedly improved with simultaneous neutralization of the C regulatory proteins CD46 (Membrane cofactor protein), CD55 (Decay-accelerating factor), and CD59 (protectin). In a retrospective study of follicular lymphoma (FL) patients, low lymphoma tissue mRNA expressions of CD59 and CD55 were associated with a good prognosis and in a progressive flow cytometry study high expression of CD20 relative to CD55 was correlated to a longer progression free survival. Gene expression profile analysis revealed that expression of certain often cell cycle, signal transduction or immune response related genes correlate with clinical outcome of FL patients. Emphasizing the role of tumor microenvironment the best differentiating genes Smad1 and EphA1 were demonstrated to be mainly expressed in the non-malignant cells of tumors. In conclusion, this thesis shows that activation of the C system is a clinically important effector mechanism of rituximab and that microenvironment factor in tumors and expression of C regulatory proteins affect markedly the efficacy of immunochemotherapy. This data can be used to identify more accurately the patients for whom immunochemotherapy is given. It may also be beneficial in development of rituximab-containing and other monoclonal antibody therapies against cancer.

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In bacteria resistance to heavy metals is mainly achieved through active efflux, but also sequestration with proteins or as insoluble compounds is used. Although numerous studies have dealt with zinc, cadmium and lead resistance mechanisms in bacteria, it has still remained unclear how different transporters are integrated into an effective homeostasis/resistance network and whether specific mechanisms for lead sequestration exist. Furthermore, since metals are toxic not only to bacteria but to higher organisms as well, it is important to be able to estimate possible biological effects of heavy metals in the environment. This could be done by determining the bioavailable amount of the metals in the environment with bacterial bioreporters. That is, one can employ bacteria that respond to metal contamination by a measurable signal to assess the property of metals to cross biological membranes and to cause harmful effects in a possibly polluted environment. In this thesis a new lead resistance mechanism is described, interplay between CBA transporters and P-type ATPases in zinc and cadmium resistance is presented and finally the acquired knowledge is used to construct bacterial bioreporters for heavy metals with increased sensitivity and specificity. The new lead resistance model employs a P-type ATPase that removes Pb2+ ions from the cytoplasm and a phosphatase that produces inorganic phosphate for lead sequestration in the periplasm. This was the first study where the molecular mechanism of lead sequestration has been described. Characterization of two P-type ATPases and two CBA transporters showed that resistance mechanisms for Zn2+ and Cd2+ are somewhat different than for Pb2+ as these metals cannot be sequestered as insoluble compounds as easily. Resistance to Zn2+ was conferred merely by the CBA transporter that could export both cytoplasmic and periplasmic ions; whereas, full resistance to Cd2+ required interplay of a P-type ATPase that exported cytoplasmic ions to periplasm and a CBA transporter that further exported periplasmic ions to the outside. The knowledge on functionality of the transporters and metal-inducible promoters was exploited in bioreporter technology. A transporter-deficient bioreporter strain that lacked exporters for Zn2+/Cd2+/Pb2+ could detect up to 45-fold lower metal concentrations than its wild type counterpart due to the accumulation of metals in the cell. The broad specificity issue of bioreporters was overcome by using Zn-specific promoter as a sensor element, thus achieving Zn-specific bioreporter.

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In Finland, barley, Hordeum vulgare L., covers 50 % of the total acreage devoted to cereal cultivation. The most common disease of barley in Finland is net blotch, a foliar disease caused by the ascomycete Pyrenophora teres Drechsler. Disease resistance based on plant genes is an environmentally friendly and economical way to manage plant diseases caused by biotic stresses. Development of a disease resistance breeding programme is dependent on knowledge of the pathogen. In addition to information on the epidemiology and virulence of a pathogen, knowledge on how the pathogen evolves and the nature of the risks that might arise in the future are essential issues that need to be taken into account to achieve the final breeding aims. The main objectives of this study were to establish reliable and efficient testing methods for Pyrenophora teres f. teres virulence screening, and to understand the role of virulence of P. teres f. teres in Finland from a disease resistance breeding point of view. The virulence of P. teres was studied by testing 239 Finnish P. teres f. teres isolates collected between 1994 2007 originating from 19 locations, and 200 P. teres progeny isolates originating from artificially produced P. teres matings. According to the results of this study, screening for P. teres f. teres isolates on barley seedlings under greenhouse conditions is a feasible and cost efficient method to describe the virulence spectrum of the pathogen. Inoculum concentration and the seedling leaf used to gauge virulence had significant effects. Barley grain size, morphological traits of P. teres isolates, spore production and growth rate on agar did not affect the expression of virulence. A common barley differential set to characterize the P. teres virulence was developed and is recommended to be used globally. The virulence spectrum of Finnish P. teres f. teres isolates collected in 1994-2007 was constant both within and between the years. The results indicated differences in the pathogen s aggressiveness and in barley genotypes resistance. However, differences in virulence were rarely significant. Unlike in laboratory conditions, no indications of changes in virulence caused by the sexual reproduction have been observed in Finnish barley fields. In Finland, durable net blotch resistance has been achieved by introducing resistance from other barley varieties using traditional crossing methods, including wide crossing, and testing the breeding material at early generations at several sites under natural infection pressure. Novel resistance is available, which is recommended to minimize the risk of selection of virulent isolates and breakdown of currently deployed resistance.