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  • Bäckström, Pia (Helsingin yliopisto, 2006)
    The characteristics of drug addiction include compulsive drug use despite negative consequences and re-occurring relapses, returns to drug use after a period of abstinence. Therefore, relapse prevention is one of the major challenges for the treatment of drug addiction. There are three main factors capable of inducing craving for drugs and triggering relapse long after cessation of drug use and dissipation of physical withdrawal signs: stress, re-exposure to the drug, and environmental stimuli (cues) that have been previously associated with drug use. The neurotransmitters dopamine and glutamate have been implicated in the modulation of drug-seeking behavior. The aim of this project was to examine the role of glutamatergic neurotransmission in relapse triggered by conditioned drug-associated stimuli. The focus was on clarifying whether relapse to drug seeking can be attenuated by blockade of glutamate receptors. In addition, as the nucleus accumbens has been proposed to participate in the modulation of drug-seeking behavior, the effects of glutamate receptor blockade in this brain structure on cue-induced relapse were investigated. The studies employed animals models in which rats were trained to press a lever in a test cage to obtain alcohol or intravenous cocaine. Drug availability was paired with distinct olfactory, auditory, or visual stimuli. This phase was followed by extinction training, during which lever presses did not result in the presentation of the drug or the drug-associated stimuli. Extinction training led to a gradual decrease in the number of lever presses during test sessions. Relapse was triggered by presenting the rats with the drug-associated stimuli in the absence of alcohol or cocaine. The drug-associated stimuli were alone capable of inducing resumption of lever pressing and maintaining this behavior during repeated testing. The number of lever presses during a session represented the intensity of drug-seeking and relapse behavior. The results suggest that glutamatergic neurotransmission is involved in the modulation of drug-seeking behavior. Both alcohol and cocaine relapse were attenuated by systemic pretreatment with glutamate receptor antagonists. However, differences were found in the ability of ionotropic AMPA/kainate and NMDA receptor antagonists to regulate drug-seeking behavior. The AMPA/kainate antagonists CNQX and NBQX, and L-701,324, an antagonist with affinity for the glycine site of the NMDA receptor, attenuated cue-induced drug seeking, whereas the competitive NMDA antagonist CGP39551 and the NMDA channel blocker MK-801 were without effect. MPEP, an antagonist at metabotropic mGlu5 glutamate receptors, also decreased drug seeking, but its administration was found to lead to conditioned suppression of behavior during subsequent treatment sessions, suggesting that MPEP may have undesirable side effects. The mGluR2/3 agonist LY379268 and the mGluR8 agonist (S)-3,4-DCPG decreased both cue-induced relapse to alcohol drinking and alcohol consumption. Control experiments showed however that administration of the agonists was accompanied by motor suppression limiting their usefulness. Administration of the AMPA/kainate antagonist CNQX, the NMDA antagonist D-AP5, and the mGluR5 antagonist MPEP into the nucleus accumbens resulted also in a decrease in drug-seeking behavior, suggesting that the nucleus accumbens is at least one of the anatomical sites regulating drug seeking and mediating the effects of glutamate receptor antagonists on this behavior.
  • Levonen, Anna-Liisa (Helsingin yliopisto, 2000)
  • Hirvonen, Tia (Helsingin yliopisto, 2014)
    Mesenchymal stem/stromal cells (MSCs) are multipotent adult stem cells that hold enormous therapeutic potential. They are currently in a focus of intense clinical and scientific investigation. MSCs are a promising cell type for various applications in the field of tissue engineering due to their multi-lineage differentiation capacity. Furthermore, one of their most interesting characteristics is that they possess immunomodulatory properties making these cells an attractive candidate for therapy of several immune-mediated disorders. MSCs are of nonembryonic origin and thus provide a less controversial and technically more feasible alternative for ESCs in future therapeutic applications. Due to their location on the cell surface, glycans are ideal molecules for identification, purification, and characterization of cells for therapeutic purposes. Methods to reliably and proficiently determine both the change in the presence of a specific glycan structures and the changes in the glycome profile of a cell, are needed. Glycan binding proteins in general serve as diagnostic tools in medical and scientific laboratories. High affinity and exquisite specificity are important factors for their successful use. The aim of this study was to characterize the glycans on the surface of MSCs in order to find novel MSC specific glycan markers. Further goal was to develop antibodies specific for MSC surface glycans, including the novel MSC marker. As described in the original publications of this study, we first characterized the glycome of MSCs and discovered that certain specific glycan epitopes are present only in MSCs, and not in cells differentiated from them. These epitopes include i antigen, which was further characterized to be a marker for umbilical cord blood derived MSCs. An antibody against the i antigen was generated using recombinant technology. Antibodies recognizing MSC surface glycans were also generated by utilizing hybridoma technology, using whole MSCs in the immunization. Taken together, these studies provide information of the changes in the glycome profile during MSC differentiation and describe a novel MSC marker. In these studies, we used two different methods to generate anti-glycan antibodies and emphasize the importance of thorough characterization of the binding properties of GBPs. The information of the characteristic glycosylation features of MSCs, and specific markers especially, can be used to isolate and characterize desired, therapeutically advantageous cell populations for distinct applications. Development of better glycan binding proteins will advance the field of cellular therapy and also the glycobiological research in general.
  • Suhonen , Lauri (Helsingin yliopisto, 2009)
    Background: Both maternal and fetal complications are increased in diabetic pregnancies. Although hypertensive complications are increased in pregnant women with pregestational diabetes, reports on hypertensive complications in women with gestational diabetes mellitus (GDM) have been contradictory. Congenital malformations and macrosomia are the main fetal complications in Type 1 diabetic pregnancies, whereas fetal macrosomia and birth trauma but not congenital malformations are increased in GDM pregnancies. Aims: To study the frequency of hypertensive disorders in gestational diabetes mellitus. To evaluate the risk of macrosomia and brachial plexus injury (Erb’s palsy) and the ability of the 2-hour glucose tolerance test (OGTT) combined with the 24-hour glucose profile to distinguish between low and high risks of fetal macrosomia among women with GDM. To evaluate the relationship between glycemic control and the risk of fetal malformations in pregnancies complicated by Type 1 diabetes mellitus. To assess the effect of glycemic control on the occurrence of preeclampsia and pregnancy-induced hypertension in Type 1 diabetic pregnancies. Subjects: A total of 986 women with GDM and 203 women with borderline glucose intolerance (one abnormal value in the OGTT) with a singleton pregancy, 488 pregnant women with Type 1 diabetes (691 pregnancies and 709 offspring), and 1154 pregnant non-diabetic women (1181 pregnancies and 1187 offspring) were investigated. Results: In a prospective study on 81 GDM patients the combined frequency of preeclampsia and PIH was higher than in 327 non-diabetic controls (19.8% vs 6.1%, p<0.001). On the other hand, in 203 women with only one abnormal value in the OGTT, the rate of hypertensive complications did not differ from that of the controls. Both GDM women and those with only one abnormal value in the OGTT had higher pre-pregnancy weights and BMIs than the controls. In a retrospective study involving 385 insulin-treated and 520 diet-treated GDM patients, and 805 non-diabetic control pregnant women, fetal macrosomia occurred more often in the insulin-treated GDM pregnancies (18.2%, p<0.001) than in the diet-treated GDM pregnancies (4.4%), or the control pregnancies (2.2%). The rate of Erb’s palsy in vaginally delivered infants was 2.7% in the insulin-treated group of women and 2.4% in the diet-treated women compared with 0.3% in the controls (p<0.001). The cesarean section rate was more than twice as high (42.3% vs 18.6%) in the insulin-treated GDM patients as in the controls. A major fetal malformation was observed in 30 (4.2%) of the 709 newborn infants in Type 1 diabetic pregnancies and in 10 (1.4%) of the 735 controls (RR 3.1, 95% CI 1.6–6.2). Even women whose levels of HbA1c (normal values less than 5.6%) were only slightly increased in early pregnancy (between 5.6 and 6.8%) had a relative risk of fetal malformation of 3.0 (95% CI 1.2–7.5). Only diabetic patients with a normal HbA1c level (<5.6%) in early pregnancy had the same low risk of fetal malformations as the controls. Preeclampsia was diagnosed in 12.8% and PIH in 11.4% of the 616 Type 1 diabetic women without diabetic nephropathy. The corresponding frequencies among the 854 control women were 2.7% (OR 5.2; 95% CI 3.3–8.4) for preeclampsia and 5.6% (OR 2.2, 95% CI 1.5–3.1) for PIH. Multiple logistic regression analysis indicated that glycemic control, nulliparity, diabetic retinopathy and duration of diabetes were statistically significant independent predictors of preeclampsia. The adjusted odds ratios for preeclampsia were 1.6 (95% CI 1.3–2.0) for each 1%-unit increment in the HbA1c value during the first trimester and 0.6 (95% CI 0.5–0.8) for each 1%-unit decrement during the first half of pregnancy. In contrast, changes in glycemic control during the second half of pregnancy did not alter the risk of preeclampsia. Conclusions: In type 1 diabetic pregnancies it is extremely important to achieve optimal glycemic control before pregnancy and maintain it throughout pregnancy in order to decrease the complication rates both in the mother and in her offspring. The rate of fetal macrosomia and birth trauma in GDM pregnancies, especially in the group of insulin-treated women, is still relatively high. New strategies for screening, diagnosing, and treatment of GDM must be developed in order to decrease fetal and neonatal complications.
  • Similä, Minna (Helsingin yliopisto, 2012)
    Type 2 diabetes prevalence is on the rise. The carbohydrates inducing a rapid postprandial elevation in blood glucose have been suggested to increase risk of type 2 diabetes. Glycemic index (GI) classifies foods based on their postprandial blood glucose response compared with the response of reference food (glucose solution or white bread). Glycemic load (GL) is a measure of both quantity and GI of carbohydrates. The aim was to investigate the associations between dietary GI, GL, and intake of high-, medium-, and low-GI carbohydrates and the risk of type 2 diabetes and to evaluate the applicability of GI to epidemiologic studies. In a postprandial study (n=11), variations in glycemic responses and GI values of foods were examined and the effects of methodologic choices on variation compared (capillary and venous sampling, white wheat bread and glucose solution as reference foods, and repeating the reference measurement). Both within-subject and between-subject variation was considerable. The variation was smaller when capillary samples were used and when the reference food was tested at least twice. The GI database was compiled for dietary GI and GL calculation for the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study participants. The GI values were obtained from the GI measurement laboratory of the National Institute for Health and Welfare and from publications meeting the methodologic criteria. The ATBC Study cohort comprised 25 943 male smokers, aged 50-69 years, among whom 1098 diabetes cases were identified from the national drug reimbursement register during a 12-year follow-up. Diet was assessed by a validated food frequency questionnaire. The relative risks (RRs) and confidence intervals (CIs) for diabetes were analyzed using Cox proportional hazard modeling, and multivariate nutrient density models were applied to examine the substitutions of macronutrients. Dietary GI and GL were not associated with diabetes risk: RR (and 95% CI) for the highest versus the lowest quintile in the multivariate model was 0.87 (0.71, 1.07) for GI and 0.88 (0.65, 1.17) for GL. Substitution of low-GI (GI≤55) carbohydrates for an isoenergetic amount of high-GI (GI≥70) carbohydrates or low-GI carbohydrates for medium-GI (56-69) carbohydrates was not associated with diabetes risk. Substitution of medium-GI carbohydrates for high-GI carbohydrates was inversely associated with diabetes risk (RR 0.75 (0.59, 0.96)). Total carbohydrate substitutions for total fat and protein were inversely associated with diabetes risk, the multivariate RRs for 2 E% substitution were 0.96 (0.94, 0.99) and 0.85 (0.80, 0.90), respectively. Carbohydrate substitution for saturated plus trans fatty acids, but not unsaturated fatty acids, was inversely associated with diabetes risk. Carbohydrate substitution for total, meat, or milk protein was associated inversely with diabetes risk, independently from GI. Within-subject and between-subject variations in measured food GI were considerable. In addition, the same total dietary GI and GL result from several different food combinations, thus reflecting different properties of the diet, not only the carbohydrate quality. These factors limit the possibilities of epidemiologic studies to observe reliable associations between glycemic effects of diet and disease risk. In this study population, GI was not associated with diabetes risk. A higher percentage of carbohydrate intake was associated with decreased diabetes risk; the risk was lowered when fat or protein was replaced with carbohydrates.
  • Väänänen, Tiina (Helsingin yliopisto, 2007)
    When genome sections of wild Solanum species are bred into the cultivated potato (S. tuberosum L.) to obtain improved potato cultivars, the new cultivars must be evaluated for their beneficial and undesirable traits. Glycoalkaloids present in Solanum species are known for their toxic as well as for beneficial effects on mammals. On the other hand, glycoalkaloids in potato leaves provide natural protection against pests. Due to breeding, glycoalkaloid profile of the plant is affected. In addition, the starch properties in potato tubers can be affected as a result of breeding, because the crystalline properties are determined by the botanical source of the starch. Starch content and composition affect the texture of cooked and processed potatoes. In order to determine glycoalkaloid contents in Solanum species, simultaneous separation of glycoalkaloids and aglycones using reversed-phase high-performance liquid chromatography (HPLC) was developed. Clean-up of foliage samples was improved using a silica-based strong cation exchanger instead of octadecyl phases in solid-phase extraction. Glycoalkaloids alpha-solanine and alpha-chaconine were detected in potato tubers of cvs. Satu and Sini. The total glycoalkaloid concentration of non-peeled and immature tubers was at an acceptable level (under 20 mg/100 g of FW) in the cv. Satu, whereas concentration in cv. Sini was 23 mg/100 g FW. Solanum species (S. tuberosum, S. brevidens, S. acaule, and S. commersonii) and interspecific somatic hybrids (brd + tbr, acl + tbr, cmm + tbr) were analyzed for their glycoalkaloid contents using liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The concentrations in the tubers of the brd + tbr and acl + tbr hybrids remained under 20 mg/100 g FW. Glycoalkaloid concentration in the foliage of the Solanum species was between 110 mg and 890 mg/100 g FW. However, the concentration in the foliage of S. acaule was as low as 26 mg/100 g FW. The total concentrations of brd + tbr, acl + tbr, and cmm + tbr hybrid foliages were 88 mg, 180 mg, and 685 mg/100 g FW, respectively. Glycoalkaloids of both parental plants as well as new combinations of aglycones and saccharides were detected in somatic hybrids. The hybrids contained mainly spirosolanes, and glycoalkaloid structures having no 5,6-double bond in the aglycone. Based on these results, the glycoalkaloid profiles of the hybrids may represent a safer and more beneficial spectrum of glycoalkaloids than that found in currently cultivated varieties. Starch nanostructure of three different cultivars (Satu, Saturna, and Lady Rosetta), a wild species S. acaule, and interspecific somatic hybrids were examined by wide-angle and small-angle X-ray scattering (WAXS, SAXS). For the first time, the measurements were conducted on fresh potato tuber samples. Crystallinity of starch, average crystallite size, and lamellar distance were determined from the X-ray patterns. No differences in the starch nanostructure between the three different cultivars were detected. However, tuber immaturity was detected by X-ray scattering methods when large numbers of immature and mature samples were measured and the results were compared. The present study shows that no significant changes occurred in the nanostructures of starches resulting from hybridizations of potato cultivars.
  • Suila, Heli (Helsingin yliopisto, 2014)
    Stem cells have a unique ability to both self-renew and differentiate into diverse cell types and they harbor remarkable potential in therapeutic applications. Stem cells can be isolated from various sources of both embryonic and adult origin. During the past decade, research on stem cells has rapidly expanded, but many issues of stem cell biology and their clinical use remain unresolved. There is a need for methods to thoroughly characterize therapeutic cell populations, to better distinguish them from other cells, and to control variation within and between different cell preparations. The surface of stem cells, like all other human cell surfaces, is covered by a complex network of glycans. This is the outmost layer of cells, called the glycocalyx. The glycocalyx is characteristic to and different in every cell type and reflects even subtle changes in cell behaviour and for example cell differentiation. Cell surface glycans are the first cellular components encountered by approaching cells, pathogens, signalling molecules and other binders, making the terminal glycan units key players in cell interactions and signalling. Due to their prominent cell surface localization, glycan epitopes can be utilized for identifying and isolating specific cell types from heterogeneous populations. The aim of this study was to characterize relevant glycan structures on umbilical cord blood derived stem and progenitor cells, to study how they are regulated and to determine their influence on stem cell biology. As decribed in the original publications of this study, we were able to characterize two novel glycan determinants, O-GlcNAc and linear poly-LacNAc, on umbilical cord blood derived mesenchymal stromal cells (UCB-MSCs). We further discovered that galectins-1 and -3 secreted by these cells are bound on the cell surface and that the cell surface galectin-1 interacts with P-selectin. This interaction is likely to play a role in the immunomodulatory homing of UCB-MSCs to sites of injury or inflammation. In addition, we present the effects and potential use of metabolic glycoengineering of UCB-MSC. Taken together, these studies provide new insights into the glycobiology of UCB derived stem and progenitor cells. This information may help to distinguish better cell populations for distinct therapeutic applications and to design therapeutic cells with enhanced biological properties.
  • Ylä-Ajos, Maria (Helsingin yliopisto, 2006)
    Muscle glycogen exists in two forms: low molecular weight pro-glycogen and high molecular weight macro-glycogen. The degradation of glycogen to glucose 1 phosphate and free glucose is catalysed by glycogen phosphorylase together with glycogen debranching enzyme (GDE). The process in which glycogen is broken down via anaerobic pathways to lactate, results in the acidification of the muscles and has a great influence on meat quality. Thus, the overall aim of this thesis was to characterise the post mortem action of GDE in muscles of meat production animals (pigs, cattle and chickens). Interest was focused on the differences in GDE activity between fast twitch glycolytic muscles and slow twitch oxidative muscles. The effects of pH, temperature, RN genotype (PRKAG3 gene), and of time post mortem on GDE activity were also investigated. This thesis showed that there are differences in GDE activity between animal species and between different muscles of an animal. It was shown that in pigs and cattle, higher GDE activity and phosphorylase activity exists in the fast twitch glycolytic muscles than in slow twitch oxidative muscles of the same animal. Thus, the high activity of these enzymes enables a faster rate of glycogenolysis in glycolytic M. longissimus dorsi compared to oxidative M. masseter. In chicken muscles, the GDE activity was low compared to pig or cattle muscles. Furthermore, the GDE activity in the glycolytic M. pectoralis superficialis was lower than in more oxidative M. quadriceps femoris despite the high phosphorylase activity in the former. The relative ratios between phosphorylase and GDE activity were higher in fast twitch glycolytic muscles than in slow twitch oxidative muscles of all studied animals. This suggests that the relatively low GDE activity compared to the phosphorylase activity in fast twitch glycolytic muscles may be a protection mechanism in living muscle against a very fast pH decrease. Chilling significantly decreased GDE activity and below 15 C porcine GDE was almost inactive. The effect of pH on GDE activity was only minor at the range normally found in post mortem muscles (pH 7.4 to 5.0). The GDE activity remained level for several hours after slaughter. During the first hours post mortem, GDE activity was similar in RN- carrier pigs and in wild type pigs. However, the GDE activity declined faster in M. longissimus dorsi from wild type pigs than in the RN carrier pigs, the difference between genotypes was significant after 24 h post mortem. Pro-glycogen and macro-glycogen contents were higher, pH decrease was faster and ultimate pH was lower in RN- carrier pigs than in wild type pigs. In the RN- carriers, the prolonged high GDE activity level may enable an extended pH decrease and lower ultimate pH in their muscles. In conclusion, GDE is not the main factor determining the rate or the extent of post mortem glycogenolysis, but under certain conditions, such as in very fast chilling, the inhibition of GDE activity in meat may reduce the rate of pH decrease and result in higher ultimate pH. The rate and extent of pH decrease affects several meat quality traits.
  • Hepojoki, Jussi (Helsingin yliopisto, 2011)
    Hantaviruses are one of the five genera of the vector-borne virus family Bunyaviridae. While other members of the family are transmitted via arthropods, hantaviruses are carried and transmitted by rodents and insectivores. Occasional transmission to humans occurs via inhalation of aerosolized rodent excreta. When transmitted to man hantaviruses cause hemorrhagic fever with renal syndrome (HFRS, in Eurasia, mortality ~10%) and hantavirus cardiopulmonary syndrome (HCPS, in the Americas, mortality ~40%). The single-stranded, negative-sense RNA genome of hantaviruses is in segments S, M and L that respectively encode for nucleocapsid (N), glycoproteins Gn and Gc, and RNA-dependent RNA-polymerase (RdRp or L protein). The genome segments, encapsidated by N protein to form ribonucleoprotein (RNP), are enclosed inside a lipid envelope decorated by spikes formed of Gn and Gc. The focus of this study was to understand the mechanisms and interactions through which the virion is formed and maintained. We observed that when extracted from virions both Gn and Gc favor homo- over hetero-oligomerization. The minimal glycoprotein complexes extracted from virion by detergent were observed, by using ultracentrifugation and gel filtration, to be tetrameric Gn and homodimeric Gc. These results led us to suggest a model where tetrameric Gn complexes are interconnected through homodimeric Gc units to form the grid-like surface architecture described for hantaviruses. This model was found to correlate with the three-dimensional (3D) reconstruction of virion surface created using cryo-electron tomography (cryo-ET). The 3D-density map showed the spike complex formed of Gn and Gc to be 10 nm high and to display a four-fold symmetry with dimensions of 15 nm times 15 nm. This unique square-shaped complex on a roughly round virion creates a hitch for the assembly, since a sphere cannot be broken into rectangles. Thus additional interactions are likely required for the virion assembly. In cryo-ET we observed that the RNP makes occasional contacts to the viral membrane, suggesting an interaction between the spike and RNP. We were able to demonstrate this interaction using various techniques, and showed that both Gn and Gc contribute to the interaction. This led us to suggest that in addition to the interactions between Gn and Gc, also the interaction between spike and RNP is required for assembly. We found galectin-3 binding protein (referred to as 90K) to co-purify with the virions and showed an interaction between 90K and the virion. Analysis of plasma samples taken from patients hospitalized for Puumala virus infection showed increased concentrations of 90K in the acute phase and the increased 90K level was found to correlate with several parameters that reflect the severity of acute HFRS. The results of these studies confirmed, but also challenged some of the dogmas on the structure and assembly of hantaviruses. We confirmed that Gn and RNP do interact, as long assumed. On the other hand we demonstrated that the glycoproteins Gn and Gc exist as homo-oligomers or appear in large hetero-oligomeric complexes, rather than form primarily heterodimers as was previously assumed. This work provided new insight into the structure and assembly of hantaviruses.
  • Saarinen, Petri (Helsingfors universitet, 2014)
    Enterococci is a group of gram positive bacteria part of human intestinal flora. While generally harmless, several species of the group are known to cause severe infections in humans, including bloodstream infections leading to sepsis. Since Enterococci are naturally resistant to many antibiotics, the use of glycopeptides, considered a”last resort” drugs, is common in treatment of enterococcal infections. In recent years, however, the emergence of glycopeptide resistant Enterococci (GRE) has been an increasing concern for clinics and microbiology laboratories around the world, creating a need for fast and accurate screening tests differentiating the glycopeptide resistant Enterococcus strains from the non-resistant ones. In this study, a combined PCR and microarray hybridization based method for identification of the clinically most prevalent GRE was established as a part of commercial sepsis diagnostic test called Prove-it™ Sepsis. Already identifying the most common Enterococcus species (E.faecium and E.faecalis), the detection of glycopeptide resistance causing ligase genes vanA and vanB and species level identification of intrinsically glycopeptide resistant E.gallinarum and E.casseliflavus were added as part of the the test. Primers were designed for sequencing vanA and vanB genes and multiple strains, provided by a Finnish clinical laboratory Huslab, were sequenced. Sequence regions unique to these genes were identified according to sequence alignment data containing the sequenced gene regions and other relevant sequences found in public sequence databases. Based on these data, primers were designed for the amplification of the selected gene regions. For identification of the amplified gene regions, a set of hybridization probes were designed and printed on microarray. In addition, probes for identifying E.casseliflavus and E.gallinarum were designed based on sequence aligment data gathered from Mobidiag Ltd. private biobank. The identification of these species was based on topoisomerase encoding gyrB gene amplified by the Prove-it™ Sepsis broad range PCR. Several primers for the amplification of vanA and vanB genes were designed and one primer pair for each was selected to be integrated to the Prove-it™ Sepsis multiplex-PCR. Similarily, multiple hybridization probes were designed for detecting vanA, vanB, E.casseliflavus and E. gallinarum. Four probes for each target gene region were selected to be integrated to the commercial test. With this modified test, 12 pure culture samples of clinical origin were tested and the results were compared to the ones provided by the laboratory of clinical microbiology of Hôspital de bicêtre (Paris, France). Results provided by the modified PCR and microarray test were identical to the reference results in 11 out of 12 cases.
  • Riikonen-Moilanen, Liisa (1983)
  • Nyström, Maria (2005)
    Gonadotropiineja vapauttava hormoni (gonadotropin-releasing hormone, GnRH) on yksi hypotalamuksen monista säätely¬hormoneista. GnRH aikaansaa luteinisoivan hormonin (LH) ja follikkeleita stimuloivan hormonin (FSH) vapautumisen adenohypofyysistä. Hypotalamus kontrolloi kiimakierron eri vaiheita GnRH-erityksen välityksellä. Ovulaatiota edeltää hypotalamuksesta erittyvä endogeeninen GnRH-aalto, joka stimuloi LH-erityksen hypofyysistä. LH-eritys aiheuttaa munasarjoissa olevien suurten follikkeleiden luteini¬saation tai ovulaation. Eksogeeninen GnRH tai sen agonistinen analogi aikaansaa endogeenisen LH- ja FSH-erityksen hypofyysistä. GnRH-injektion aiheuttamaa ovulaation induktiota on käytetty kiimakiertojen käynnistämiseen poikimisen jälkeen, kiiman-synkronointiohjelmissa ja siemennyksen yhteydessä tiinehtyvyyden parantamiseksi sekä terveillä lehmillä aloitussiemennyksen yhteydessä että oireettomilla uusijoilla. GnRH:ta käytetään myös munasarjarakkuloiden hoidossa, ja sitä käytetään yhdistettynä prostaglandiiniin, progesteroniin ja / tai estradioliin poikimisen jälkeisen kiimattomuuden hoidossa. Normaalia lyhyempiä kiimakiertoja saattaa esiintyä ensimmäisen ovulaation yhteydessä hiehoilla puberteetissa ja lehmillä poiki¬misen jälkeen. GnRH-injektio annettuna samanaikaisesti prostaglandiini-injektion kanssa tai 24 tuntia prostaglandiini-injektion jälkeen voi aikaansaada lyhyitä kiimakiertoja normaalisti sykloivilla hiehoilla ja lehmillä. Nämä lyhyet kiimakierrot poikkeavat puberteetissa ja poikimisen jälkeen esiintyvistä lyhyistä kiimakierroista siten, että näitä GnRH- ja PGF2a-hoidolla aikaan saatuja lyhyitä kiimakiertoja edeltää normaali progesteronivaihe, jonka pitäisi estää lyhyiden kiimakiertojen esiintyminen. Kokeellisen tutkimuksen tavoitteena oli selvittää, vaikuttaako GnRH-annos (gonadoreliini 100 µg vs. 500 µg), ja siten LH-aallon suuruus, indusoitujen lyhyiden kiimakiertojen esiintymiseen sykloivilla hiehoilla (n=19). Hiehot jaettiin satunnaisesti kahteen hoitoryhmään. Toiselle ryhmälle (n=10) annettiin 24 tuntia prostaglandiini-injektiosta 100 µg gonadoreliiniä ja toiselle ryhmälle (n=15) 500 µg gonadoreliiniä. Koe suoritettiin kahteen kertaan. Lisäksi määritettiin myös progesteroni- ja LH-pitoisuudet hiehojen verestä. GnRH-annoksen suuruus ei vaikuttanut lyhyiden kiimakiertojen esiintyvyyteen. Ei ollut tilastollisesti merkitseviä eroja 100 µg ja 500 µg GnRH-annoksen jälkeen esiintyvien lyhyiden kiimakiertojen insidenssissä. Hiehoilla, joilla oli normaalia lyhyempi kiimakierto, progesteronipitoisuus saavutti korkeimman arvonsa 3 - 6 päivää ovulaatiosta. Hiehoilla, joilla oli normaalin pituinen kiimakierto, suurin progesteronipitoisuus saavutettiin keskimäärin 14 päivää ovulaatiosta. GnRH-annos (100 vs. 500 µg) ei tilastollisesti merkitsevästi vaikuttanut LH-pitoisuuksiin tai LH-käyrän muotoon. Tämä oli yllättävää, koska ennakkokäsityksenä oli, että GnRH-annoksen kasvattaminen olisi ollut lisännyt LH-eritystä.
  • Lindberg, Mats (2008)
    Denna avhandling ar en studie av verksamheten hos en organisation, Sydspetsens Nyforetagarcentral r.f. i Vastra Nyland. Foreningens verksamhetside ar att tillhandahalla jamlikt och objektivt radgivningstjanster for personer som onskar utvardera sin affarside och verksamhetsforutsattningar i syfte att eventuelit inleda foretagsverksamhet. Avhandlingens syfte ar att forklara varfor foretag grundade efter konsultering hos Nyforetagarcentralen overlever i hogre grad an foretag i allmanhet. Ur samhallssynvinkel ar sunda foretag en forutsattning for uppratthallandet av valfarden. Forskningsansatsen begransas till att ur anvandarperspektiv utvardera verksamheten. Teori om utvardering, narmast utvarderingsteori om organisationer, bildar avhandlingens teoretiska referensram. Som stud for den konkreta utvarderingen tillampas brukarmodellen. Utskick av enkater eller insamlande av motsvarande undersokningsmaterial har omojliggjorts pa grund av sekretess, behovliga kontaktuppgifter har inte lamnats ut. Behovligt forskningsmaterial har tillhandahallits av foreningen i form av tidigare gjord kundundersokning. Undersokningen har utforts 2007. Den aktuella avhandlingen har fardigstallts under varen 2008. Resultatet for forskningen visar att kompetens, tjansternas tillganglighet och verksamhetssatt forklarar effektiviteten. Emellertid beaktar forskningen inte faktorer sasom radande konjunkturlage eller eventuella forandringar i den lokala foretagskulturen som forklaringsfaktorer. Den gjorda utvarderingsforskningen bor darfor ses som eft forsok att lyfta fram den bedrivna verksamheten hos Sydspetsens Nyforetagarcentral r.f som en delforklaring till varfor overlevnadsgraden bland de foretag som konsulterat organisationen tenderar att vara hogre an vad allmant ar. Resultatet av forskningen forklarar inte alit utan ska ses som en del av en storre forklaringsproblematik.
  • Lepojärvi, Jason (Helsingin yliopisto, 2015)
    C. S. Lewis (1898-1963) was one of the most influential Christian thinkers of the twentieth century with continuing relevance into the twenty-first. Despite growing academic interest in Lewis, many fields of inquiry remain largely unmapped in Lewis scholarship today. This compilation dissertation, consisting of an introductory overview together with four stand-alone but connected essays, extends critical understanding of Lewis's contribution to the theology of love. In three of the four essays, Lewis's theology of love is compared to and contrasted with that of Anders Nygren (1890-1978); and in one, that of Augustine of Hippo. Using systematic textual analysis, the essays evaluate Lewis's key concepts, argumentation, and presuppositions. Nygren, the Swedish Lutheran theologian and bishop of Lund, has virtually dominated modern theological discussion of love. His antithesis between selfless and gratuitous Christian love and self-seeking and needful Pagan love, or agape and eros respectively, became enormously influential in twentieth century theology. Lewis was initially shaken up by Nygren's work, and it took him decades to formulate his own model, above all in Surprised by Joy (1955) and The Four Loves (1960). It is shown that Lewis constructed not only his theology of love, but also his theology of spiritual desire as a form of love, in conscious opposition to Nygren. Lewis's theology of love challenges the denigration of eros and its separation from agape. Nygren's predestinarianism is also rejected. Lewis devises his own vocabulary, avoids the use of eros and agape in Nygren's sense, and hardly ever mentions Nygren by name. All this suggests a deliberate apologetic strategy to bypass certain defences of his readers and to avoid Nygren-dependency. Despite their incommensurate love-taxonomies, Lewis's need-love/gift-love and Nygren's eros/agape have often been treated as parallels. This longstanding assumption is shown to be in need of greater nuance. The study demonstrates that Lewis's concept of spiritual longing, which he calls Joy, is relevant to the Nygren debate and serves as a potent variant for Nygren's eros. However, no one thing in Lewis's mental repertoire can serve as a perfect translation of Nygren's eros, because for Lewis it is an abstract caricature cut off from real life. In Lewis's theological vision, contra Nygren, spiritual longing, far from obfuscating the Gospel, is a God-given desire that prepares the way for it. Lewis is not free from the occasional hyperbole or blind spot. For instance, his argument that romantic love is not eudaimonistic is shown to be somewhat convoluted, and his famous disagreement with Augustine is possibly based on a misunderstanding. A perennial feature in Lewis's understanding of love, reflected in all four essays, is the ambiguity of love. Love is not something pejorative, but neither is it an infallible moral compass. God is love, but love is not God.
  • Karhu, Helena (1955)
  • Koskinen, Kalervo (1931)
  • Soininen, Ilmari (2012)
    The economies of East Asia, notably China, South Korea and Vietnam, have undergone significant industrial transformations over the last several decades. The rapid transition from largely low-productivity, agriculture-based to high-productivity, modern economies was built on a foundation of manufactured exports to the developed world. In contrast, the economies of Sub-Saharan Africa are still largely resource-based, with little manufacturing export activity. This thesis examines the potential role of exchange rate policy in promoting the manufactured export sector in Africa. Both empirical and theoretical work suggests undervalued domestic currencies played a key role in promoting the growth of manufactured exports in East Asia. The thesis begins by looking at why manufactured exports are important for economic development, looking at both empirical findings and the theoretical underpinnings. The role of exchange rates in the industrialization process is examined, with presentation of both empirical work and an in-depth look at two theoretical models. These findings are then used to assess the potential for a successful strategy of currency undervaluation in Africa. The main finding of the thesis is that such a strategy seems difficult both in terms of economic fundamentals and political reality and could present significant issues going forward.
  • Lindroos, Linda (2013)
    III-V nanowires (NWs) are emerging as a new class of interesting nanostructures that hold promising potential for future generation electronic and optoelectronic devices. NWs are most often grown epitaxially via the vapor-liquid-solid (VLS) mechanism, which allows, in ideal case, an accurate control of diameter, length, crystal phase, doping concentration and junction formation. The biggest challenge in the field of NWs is, however, the controlled growth and understanding of the underlying mechanism. The aim of the experimental part in this work was to optimize the growth parameters and to improve the optical properties of Au assisted growth of InP NWs on silicon and glass substrates using atmospheric pressure metal-organic vapor phase epitaxy (MOVPE). The growth parameters of InP NWs on Si (111) substrate were optimized in terms of substrate pre-treatments, growth temperature, V/III ratio, and Zn doping. Consistent with the earlier results, all the growth parameters were found to affect the morphological and optical quality of the NWs. In addition, the NWs exhibited a strong quantum confinement for diameters below 20 nm. To improve the optical properties, surface passivation of InP NWs was investigated. Core-shell structures were formed both in situ with MOVPE and ex situ with atomic layer deposition (ALD). Growth of InP NWs on low-cost glass substrates was also studied and encouraging results were achieved. The results in this work can be used as a basis for further studies of more complex InP-based NWs.