Noncommutative Gravitation as a Gauge Theory of Twisted Poincaré Symmetry

Gravitaation kvanttiteorian muotoilu on ollut teoreettisten fyysikkojen tavoitteena kvanttimekaniikan synnystä lähtien. Kvanttimekaniikan soveltaminen korkean energian ilmiöihin yleisen suhteellisuusteorian viitekehyksessä johtaa aika-avaruuden koordinaattien operatiiviseen ei-kommutoivuuteen. Ei-kommutoivia aika-avaruuden geometrioita tavataan myös avointen säikeiden säieteorioiden tietyillä matalan energian rajoilla. Ei-kommutoivan aika-avaruuden gravitaatioteoria voisi olla yhteensopiva kvanttimekaniikan kanssa ja se voisi mahdollistaa erittäin lyhyiden etäisyyksien ja korkeiden energioiden prosessien ei-lokaaliksi uskotun fysiikan kuvauksen, sekä tuottaa yleisen suhteellisuusteorian kanssa yhtenevän teorian pitkillä etäisyyksillä. Tässä työssä tarkastelen gravitaatiota Poincarén symmetrian mittakenttäteoriana ja pyrin yleistämään tämän näkemyksen ei-kommutoiviin aika-avaruuksiin. Ensin esittelen Poincarén symmetrian keskeisen roolin relativistisessa fysiikassa ja sen kuinka klassinen gravitaatioteoria johdetaan Poincarén symmetrian mittakenttäteoriana kommutoivassa aika-avaruudessa. Jatkan esittelemällä ei-kommutoivan aika-avaruuden ja kvanttikenttäteorian muotoilun ei-kommutoivassa aika-avaruudessa. Mittasymmetrioiden lokaalin luonteen vuoksi tarkastelen huolellisesti mittakenttäteorioiden muotoilua ei-kommutoivassa aika-avaruudessa. Erityistä huomiota kiinnitetään näiden teorioiden vääristyneeseen Poincarén symmetriaan, joka on ei-kommutoivan aika-avaruuden omaama uudentyyppinen kvanttisymmetria. Seuraavaksi tarkastelen ei-kommutoivan gravitaatioteorian muotoilun ongelmia ja niihin kirjallisuudessa esitettyjä ratkaisuehdotuksia. Selitän kuinka kaikissa tähänastisissa lähestymistavoissa epäonnistutaan muotoilla kovarianssi yleisten koordinaattimunnosten suhteen, joka on yleisen suhteellisuusteorian kulmakivi. Lopuksi tutkin mahdollisuutta yleistää vääristynyt Poincarén symmetria lokaaliksi mittasymmetriaksi --- gravitaation ei-kommutoivan mittakenttäteorian saavuttamisen toivossa. Osoitan, että tällaista yleistystä ei voida saavuttaa vääristämällä Poincarén symmetriaa kovariantilla twist-elementillä. Näin ollen ei-kommutoivan gravitaation ja vääristyneen Poincarén symmetrian tutkimuksessa tulee jatkossa keskittyä muihin lähestymistapoihin.

Synthesis of neoglycoconjugates and oligosaccharides with potential anti-Helicobacter pylori activity

The significance of carbohydrate-protein interactions in many biological phenomena is now widely acknowledged and carbohydrate based pharmaceuticals are under intensive development. The interactions between monomeric carbohydrate ligands and their receptors are usually of low affinity. To overcome this limitation natural carbohydrate ligands are often organized as multivalent structures. Therefore, artificial carbohydrate pharmaceuticals should be constructed on the same concept, as multivalent carbohydrates or glycoclusters. Infections of specific host tissues by bacteria, viruses, and fungi are among the unfavorable disease processes for which suitably designed carbohydrate inhibitors represent worthy targets. The bacterium Helicobacter pylori colonizes more than half of all people worldwide, causing gastritis, gastric ulcer, and conferring a greater risk of stomach cancer. The present medication therapy for H. pylori includes the use of antibiotics, which is associated with increasing incidence of bacterial resistance to traditional antibiotics. Therefore, the need for an alternative treatment method is urgent. In this study, four novel synthesis procedures of multivalent glycoconjugates were created. Three different scaffolds representing linear (chondroitin oligomer), cyclic (γ-cyclodextrin), and globular (dendrimer) molecules were used. Multivalent conjugates were produced using the human milk type oligosaccharides LNDFH I (Lewis-b hexasaccharide), LNnT (Galβ1-4GlcNAcβ1-3Galβ1-4Glc), and GlcNAcβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glc all representing analogues of the tissue binding epitopes for H. pylori. The first synthetic method included the reductive amination of scaffold molecules modified to express primary amine groups, and in the case of dendrimer direct amination to scaffold molecule presenting 64 primary amine groups. The second method described a direct procedure for amidation of glycosylamine modified oligosaccharides to scaffold molecules presenting carboxyl groups. The final two methods that were created both included an oxime-linkage on linkers of different length. All the new synthetic procedures synthesized had the advantage of using unmodified reducing sugars as starting material making it easy to synthesize glycoconjugates of different specificity. In addition, the binding activity of an array of neoglycolipids to H. pylori was studied. Consequently, two new neolacto-based structures, Glcβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glcβ1-Cer and GlcAβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glcβ1-Cer, with binding activity toward H. pylori were discovered. Interestingly, N-methyl and N-ethyl amide modification of the GlcAβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4Glcβ1-Cer glucuronic acid residue resulted in more effective H. pylori binding epitopes than the parent molecule.

Microneurovascular free muscle transfer with cross-over nerve grafts in facial reanimation

Microneurovascular free muscle transfer with cross-over nerve grafts in facial reanimation Loss of facial symmetry and mimetic function as seen in facial paralysis has an enormous impact on the psychosocial conditions of the patients. Patients with severe long-term facial paralysis are often reanimated with a two-stage procedure combining cross-facial nerve grafting, and 6 to 8 months later with microneurovascular (MNV) muscle transfer. In this thesis, we recorded the long-term results of MNV surgery in facial paralysis and observed the possible contributing factors to final functional and aesthetic outcome after this procedure. Twenty-seven out of forty patients operated on were interviewed, and the functional outcome was graded. Magnetic resonance imaging (MRI) of MNV muscle flaps was done, and nerve graft samples (n=37) were obtained in second stage of the operation and muscle biopsies (n=18) were taken during secondary operations.. The structure of MNV muscles and nerve grafts was evaluated using histological and immunohistochemical methods ( Ki-67, anti-myosin fast, S-100, NF-200, CD-31, p75NGFR, VEGF, Flt-1, Flk-1). Statistical analysis was performed. In our studies, we found that almost two-thirds of the patients achieved good result in facial reanimation. The longer the follow-up time after muscle transfer the weaker was the muscle function. A majority of the patients (78%) defined their quality of life improved after surgery. In MRI study, the free MNV flaps were significantly smaller than originally. A correlation was found between good functional outcome and normal muscle structure in MRI. In muscle biopsies, the mean muscle fiber diameter was diminished to 40% compared to control values. Proliferative activity of satellite cells was seen in 60% of the samples and it tended to decline with an increase of follow-up time. All samples showed intramuscular innervation. Severe muscle atrophy correlated with prolonged intraoperative ischaemia. The good long-term functional outcome correlated with dominance of fast fibers in muscle grafts. In nerve grafts, the mean number of viable axons amounted to 38% of that in control samples. The grafted nerves characterized by fibrosis and regenerated axons were thinner than in control samples although they were well vascularized. A longer time between cross facial nerve grafting and biopsy sampling correlated with a higher number of viable axons. P75Nerve Growth Factor Receptor (p75NGFR) was expressed in every nerve graft sample. The expression of p75NGFR was lower in older than in younger patients. A high expression of p75NGFR was often seen with better function of the transplanted muscle. In grafted nerve Vascular Endothelial Growth Factor (VEGF) and its receptors were expressed in nervous tissue. In conclusion, most of the patients achieved good result in facial reanimation and were satisfied with the functional outcome. The mimic function was poorer in patients with longer follow-up time. MRI can be used to evaluate the structure of the microneurovascular muscle flaps. Regeneration of the muscle flaps was still going on many years after the transplantation and reinnervation was seen in all muscle samples. Grafted nerves were characterized by fibrosis and fewer, thinner axons compared to control nerves although they were well vascularized. P75NGFR and VEGF were expressed in human nerve grafts with higher intensity than in control nerves which is described for the first time.

Anti-TNF treatment in juvenile idiopathic arthritis and associated uveitis : Clinical perspectives on growth, uveitis, and drug survival

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of childhood chronic arthritides, associated with chronic uveitis in 20% of cases. For JIA patients responding inadequately to conventional disease-modifying anti-rheumatic drugs (DMARDs), biologic therapies, anti-tumor necrosis factor (anti-TNF) agents are available. In this retrospective multicenter study, 258 JIA-patients refractory to DMARDs and receiving biologic agents during 1999-2007 were included. Prior to initiation of anti-TNFs, growth velocity of 71 patients was delayed in 75% and normal in 25%. Those with delayed growth demonstrated a significant increase in growth velocity after initiation of anti-TNFs. Increase in growth rate was unrelated to pubertal growth spurt. No change was observed in skeletal maturation before and after anti-TNFs. The strongest predictor of change in growth velocity was growth rate prior to anti-TNFs. Change in inflammatory activity remained a significant predictor even after decrease in glucocorticoids was taken into account. In JIA-associated uveitis, impact of two first-line biologic agents, etanercept and infliximab, and second-line or third-line anti-TNF agent, adalimumab, was evaluated. In 108 refractory JIA patients receiving etanercept or infliximab, uveitis occurred in 45 (42%). Uveitis improved in 14 (31%), no change was observed in 14 (31%), and in 17 (38%) uveitis worsened. Uveitis improved more frequently (p=0.047) and frequency of annual uveitis flares was lower (p=0.015) in those on infliximab than in those on etanercept. In 20 patients taking adalimumab, 19 (95%) had previously failed etanercept and/or infliximab. In 7 patients (35%) uveitis improved, in one (5%) worsened, and in 12 (60%) no change occurred. Those with improved uveitis were younger and had shorter disease duration. Serious adverse events (AEs) or side-effects were not observed. Adalimumab was effective also in arthritis. Long-term drug survival (i.e. continuation rate on drug) with etanercept (n=105) vs. infliximab (n=104) was at 24 months 68% vs. 68%, and at 48 months 61% vs. 48% (p=0.194 in log-rank analysis). First-line anti-TNF agent was discontinued either due to inefficacy (etanercept 28% vs. infliximab 20%, p=0.445), AEs (7% vs. 22%, p=0.002), or inactive disease (10% vs. 16%, p=0.068). Females, patients with systemic JIA (sJIA), and those taking infliximab as the first therapy were at higher risk for treatment discontinuation. One-third switched to the second anti-TNF agent, which was discontinued less often than the first. In conclusion, in refractory JIA anti-TNFs induced enhanced growth velocity. Four-year treatment survival was comparable between etanercept and infliximab, and switching from first-line to second-line agent a reasonable therapeutic option. During anti-TNF treatment, one-third with JIA-associated anterior uveitis improved.

Asteroid identification using statistical orbital inversion methods

An efficient and statistically robust solution for the identification of asteroids among numerous sets of astrometry is presented. In particular, numerical methods have been developed for the short-term identification of asteroids at discovery, and for the long-term identification of scarcely observed asteroids over apparitions, a task which has been lacking a robust method until now. The methods are based on the solid foundation of statistical orbital inversion properly taking into account the observational uncertainties, which allows for the detection of practically all correct identifications. Through the use of dimensionality-reduction techniques and efficient data structures, the exact methods have a loglinear, that is, O(nlog(n)), computational complexity, where n is the number of included observation sets. The methods developed are thus suitable for future large-scale surveys which anticipate a substantial increase in the astrometric data rate. Due to the discontinuous nature of asteroid astrometry, separate sets of astrometry must be linked to a common asteroid from the very first discovery detections onwards. The reason for the discontinuity in the observed positions is the rotation of the observer with the Earth as well as the motion of the asteroid and the observer about the Sun. Therefore, the aim of identification is to find a set of orbital elements that reproduce the observed positions with residuals similar to the inevitable observational uncertainty. Unless the astrometric observation sets are linked, the corresponding asteroid is eventually lost as the uncertainty of the predicted positions grows too large to allow successful follow-up. Whereas the presented identification theory and the numerical comparison algorithm are generally applicable, that is, also in fields other than astronomy (e.g., in the identification of space debris), the numerical methods developed for asteroid identification can immediately be applied to all objects on heliocentric orbits with negligible effects due to non-gravitational forces in the time frame of the analysis. The methods developed have been successfully applied to various identification problems. Simulations have shown that the methods developed are able to find virtually all correct linkages despite challenges such as numerous scarce observation sets, astrometric uncertainty, numerous objects confined to a limited region on the celestial sphere, long linking intervals, and substantial parallaxes. Tens of previously unknown main-belt asteroids have been identified with the short-term method in a preliminary study to locate asteroids among numerous unidentified sets of single-night astrometry of moving objects, and scarce astrometry obtained nearly simultaneously with Earth-based and space-based telescopes has been successfully linked despite a substantial parallax. Using the long-term method, thousands of realistic 3-linkages typically spanning several apparitions have so far been found among designated observation sets each spanning less than 48 hours.

Lightcurve inversion for asteroid spins and shapes

Knowledge of the physical properties of asteroids is crucial in many branches of solar-system research. Knowledge of the spin states and shapes is needed, e.g., for accurate orbit determination and to study the history and evolution of the asteroids. In my thesis, I present new methods for using photometric lightcurves of asteroids in the determination of their spin states and shapes. The convex inversion method makes use of a general polyhedron shape model and provides us at best with an unambiguous spin solution and a convex shape solution that reproduces the main features of the original shape. Deriving information about the non-convex shape features is, in principle, also possible, but usually requires a priori information about the object. Alternatively, a distribution of non-convex solutions, describing the scale of the non-convexities, is also possible to be obtained. Due to insufficient number of absolute observations and inaccurately defined asteroid phase curves, the $c/b$-ratio, i.e., the flatness of the shape model is often somewhat ill-defined. However, especially in the case of elongated objects, the flatness seems to be quite well constrained, even in the case when only relative lightcurves are available. The results prove that it is, contrary to the earlier misbelief, possible to derive shape information from the lightcurve data if a sufficiently wide range of observing geometries is covered by the observations. Along with the more accurate shape models, also the rotational states, i.e., spin vectors and rotation periods, are defined with improved accuracy. The shape solutions obtained so far reveal a population of irregular objects whose most descriptive shape characteristics, however, can be expressed with only a few parameters. Preliminary statistical analyses for the shapes suggests that there are correlations between shape and other physical properties, such as the size, rotation period and taxonomic type of the asteroids. More shape data of, especially, the smallest and largest asteroids, as well as the fast and slow rotators is called for in order to be able to study the statistics more thoroughly.

Kansalaisvaikuttamista? Habermasilaisen julkisuusteorian anti suomalaiselle ympäristöliikkeelle

Tässä pro gradu -tutkielmassa analysoidaan suomalaista ympäristöliikettä Jürgen Habermasin julkisuuden käsitteen näkökulmasta. Työn tutkimusongelmana on tarkastella julkisuutta ympäristövaikuttamisen keinona. Ponnahduslautana tutkimuksessa käytetään 2000-luvun Lapin metsien käyttöä koskevia kiistoja, joiden ratkomisyrityksiin moni Suomessa toimiva ympäristöjärjestö on osallistunut. Pitkään ratkaisemattomina olleet kiistat ovat johtaneet tilanteeseen, jossa on perusteltua kysyä, mikä ongelmien selvittämisessä on mennyt pieleen. Olisiko ennen kaikkea ammattimaiseen ja institutionalisoituneeseen vaikuttamiseen nojanneet ympäristöjärjestöt voineet toimia kiistojen yhteydessä jollakin vaihtoehtoisella tavalla? Vaihtoehdoksi esitetään Jürgen Habermasin tarjoamaa julkisuuden mallia, jonka on nähty olevan keskeinen modernin yhteiskunnan mahdollisuuksia ja rajoitteita arvioitaessa. Käsitys julkisuudesta sisältää ajatuksen kriittiseen keskusteluun pohjautuvasta, kaikille avoimesta kansalaisvaikuttamisesta. Näin muodostuneesta yleisestä mielipiteestä tulee poliittisen päätöksenteon ohjenuora. Julkisuuden ihanteen rinnalla Habermasin teoria sisältää kuvauksen julkisuuden rakennemuutoksesta – kriittisen julkisuuden alennustilasta myöhäiskapitalistisessa kulutusyhteiskunnassa. Tässä tutkimuksessa käytän näitä kahta teoreettista näkökulmaa arvioidessani nykyaikaista ympäristövaikuttamista. Keskeisin lähdeteos on Habermasin Julkisuuden rakennemuutos ja sen teoreettista perinnettä jatkaneet tutkimukset. Aineistoni koostuu kuudesta teemahaastattelusta, jotka toteutettiin keväällä 2009 Greenpeacessa, Suomen luonnonsuojeluliitossa ja WWF:ssä. Tutkimusmenetelmänä käytän teemoittelua. Sen tuloksena esiin nousevista teemoista keskeisin kertoo ympäristöjärjestöjen ammattimaistumisesta. Tulosteni mukaan ympäristövaikuttamista leimaa institutionalisoituneisuus ja hallinnollisuus, jolloin julkisuusperiaatteen toimintaedellytykset ovat heikentyneet. Julkisuuden käsitteelle löytyy kuitenkin myös varovaista tilausta suomalaisten ympäristöjärjestöjen keskuudessa.

Pre-eclampsia : The role of soluble VEGF receptor-1 and related anti-angiogenic factors beyond

Pre-eclampsia is a pregnancy complication that affects about 5% of all pregnancies. It is known to be associated with alterations in angiogenesis -related factors, such as vascular endothelial growth factor (VEGF). An excess of antiangiogenic substances, especially the soluble receptor-1 of VEGF (sVEGFR-1), has been observed in maternal circulation after the onset of the disease, probably reflecting their increased placental production. Smoking reduces circulating concentrations of sVEGFR-1 in non-pregnant women, and in pregnant women it reduces the risk of pre-eclampsia. Soluble VEGFR-1 acts as a natural antagonist of VEGF and placental growth factor (PlGF) in human circulation, holding a promise for potential therapeutic use. In fact, it has been used as a model to generate a fusion protein, VEGF Trap , which has been found effective in anti-angiogenic treatment of certain tumors and ocular diseases. In the present study, we evaluated the potential use of maternal serum sVEGFR-1, Angiopoietin-2 (Ang-2) and endostatin, three central anti-angiogenic markers, in early prediction of subsequent pre-eclampsia. We also studied whether smoking affects circulating sVEGFR-1 concentrations in pregnant women or their first trimester placental secretion and expression in vitro. Last, in order to allow future discussion on the potential therapy based on sVEGFR-1, we determined the biological half-life of endogenous sVEGFR-1 in human circulation, and measured the concomitant changes in free VEGF concentrations. Blood or placental samples were collected from a total of 268 pregnant women between the years 2001 2007 in Helsinki University Central Hospital for the purposes above. The biomarkers were measured using commercially available enzyme-linked immunosorbent assays (ELISA). For the analyses of sVEGFR-1, Ang-2 and endostatin, a total of 3 240 pregnant women in the Helsinki area were admitted to blood sample collection during two routine ultrasoundscreening visits at 13.7 ± 0.5 (mean ± SD) and 19.2 ± 0.6 weeks of gestation. Of them, 49 women later developing pre-eclampsia were included in the study. Their disease was further classified as mild in 29 and severe in 20 patients. Isolated early-onset intrauterine growth retardation (IUGR) was diagnosed in 16 women with otherwise normal medical histories and uncomplicated pregnancies. Fifty-nine women remaining normotensive, non-proteinuric and finally giving birth to normal-weight infants were picked to serve as the control population of the study. Maternal serum concentrations of Ang-2, endostatin and sVEGFR-1, were increased already at 16 20 weeks of pregnancy, about 13 weeks before the clinical manifestation of preeclampsia. In addition, these biomarkers could be used to identify women at risk with a moderate precision. However, larger patient series are needed to determine whether these markers could be applied for clinical use to predict preeclampsia. Intrauterine growth retardation (IUGR), especially if noted at early stages of pregnancy and not secondary to any other pregnancy complication, has been suggested to be a form of preeclampsia compromising only the placental sufficiency and the fetus, but not affecting the maternal endothelium. In fact, IUGR and preeclampsia have been proposed to share a common vascular etiology in which factors regulating early placental angiogenesis are likely to play a central role. Thus, these factors have been suggested to be involved in the pathogenesis of IUGR. However, circulating sVEGFR-1, Ang-2 and endostatin concentrations were unaffected by subsequent IUGR at early second trimester. Furthermore, smoking was not associated with alterations in maternal circulating sVEGFR-1 or its placental production. The elimination of endogenous sVEGFR-1 after pregnancy was calculated from serial samples of eight pregnant women undergoing elective Caesarean section. As typical for proteins in human compartments, the elimination of sVEGFR-1 was biphasic, containing a rapid halflife of 3.4 h and a slow one of 29 h. The decline in sVEGFR-1 concentrations after mid-trimester legal termination of pregnancy was accompanied with a simultaneous increase in the serum levels of free VEGF so that within a few days after pregnancy VEGF dominated in the maternal circulation. Our study provides novel information on the kinetics of endogenous sVEGFR-1, which serves as a potential tool in the development of new strategies against diseases associated with angiogenic imbalance and alterations in VEGF signaling.