Factor V Leiden as risk factor for pregnancy complications : Epidemiological study of Finnish women

Factor V Leiden (FV Leiden) is the most common inherited thrombophilia in Caucasians increasing the risk for venous thrombosis. Its prevalence in Finland is 2-3%. FV Leiden has also been associated with several pregnancy complications. However, the importance of FV Leiden as their risk factor is unclear. The aim of the study was to assess FV Leiden as a risk factor for pregnancy complications in which prothrombotic mechanisms may play a part. Specifically, the study aimed to assess the magnitude of the risk, if any, associated with FV Leiden for pregnancy-associated venous thrombosis, pre-eclampsia, unexplained stillbirth, and preterm birth. The study was conducted as a nested case-control study within a fixed cohort of 100,000 consecutive pregnant women in Finland. The study was approved by the ethics committee of the Finnish Red Cross Blood Service and by the Ministry of Social Affairs and Health. All participants gave written informed consent. Cases and controls were identified by using national registers. The diagnoses of the 100,000 women identified from the National Register of Blood Group and Blood Group Antibodies of Pregnant Women were obtained from the National Hospital Discharge Register. Participants gave blood samples for DNA tests and filled in questionnaires. The medical records of the participants were reviewed in 49 maternity hospitals in Finland. Genotyping was performed in the Finnish Genome Center. When evaluating pregnancy-associated venous thrombosis (34 cases, 641 controls), FV Leiden was associated with 11-fold risk (OR 11.6, 95% CI 3.6-33.6). When only analyzing women with first venous thrombosis, the risk was 6-fold (OR 5.8, 95% CI 1.6-21.8). The risk was increased by common risk factors, the risk being highest in women with FV Leiden and pre-pregnancy BMI over 30 kg/m2 (75-fold), and in women with FV Leiden and age over 35 years (60-fold). When evaluating pre-eclampsia (248 cases, 679 controls), FV Leiden was associated with a trend of increased risk (OR 1.7, 95% CI 0.8-3.9), but the association was not statistically significant. When evaluating unexplained stillbirth (44 cases, 776 controls), FV Leiden was associated with over 3-fold risk (OR 3.8, 95% CI 1.2-11.6). When evaluating preterm birth (324 cases, 752 controls), FV Leiden was associated with over 2-fold risk (OR 2.4, 95% CI 1.3-4.6). FV Leiden was especially associated with late preterm birth (32-36 weeks of gestation), but not with early preterm birth (< 32 weeks of gestation). The results of this large population-based study can be generalized to Finnish women with pregnancies continuing beyond first trimester, and may be applied to Caucasian women in populations with similar prevalence of FV Leiden and high standard prenatal care.

Mammalian Mat1 subunit of Transcription Factor IIH in gene-specific and general transcription

All protein-encoding genes in eukaryotes are transcribed into messenger RNA (mRNA) by RNA Polymerase II (RNAP II), whose activity therefore needs to be tightly controlled. An important and only partially understood level of regulation is the multiple phosphorylations of RNAP II large subunit C-terminal domain (CTD). Sequential phosphorylations regulate transcription initiation and elongation, and recruit factors involved in co-transcriptional processing of mRNA. Based largely on studies in yeast models and in vitro, the kinase activity responsible for the phosphorylation of the serine-5 (Ser5) residues of RNAP II CTD has been attributed to the Mat1/Cdk7/CycH trimer as part of Transcription Factor IIH. However, due to the lack of good mammalian genetic models, the roles of both RNAP II Ser5 phosphorylation as well as TFIIH kinase in transcription have provided ambiguous results and the in vivo kinase of Ser5 has remained elusive. The primary objective of this study was to elucidate the role of mammalian TFIIH, and specifically the Mat1 subunit in CTD phosphorylation and general RNAP II-mediated transcription. The approach utilized the Cre-LoxP system to conditionally delete murine Mat1 in cardiomyocytes and hepatocytes in vivo and and in cell culture models. The results identify the TFIIH kinase as the major mammalian Ser5 kinase and demonstrate its requirement for general transcription, noted by the use of nascent mRNA labeling. Also a role for Mat1 in regulating general mRNA turnover was identified, providing a possible rationale for earlier negative findings. A secondary objective was to identify potential gene- and tissue-specific roles of Mat1 and the TFIIH kinase through the use of tissue-specific Mat1 deletion. Mat1 was found to be required for the transcriptional function of PGC-1 in cardiomyocytes. Transriptional activation of lipogenic SREBP1 target genes following Mat1 deletion in hepatocytes revealed a repressive role for Mat1apparently mediated via co-repressor DMAP1 and the DNA methyltransferase Dnmt1. Finally, Mat1 and Cdk7 were also identified as a negative regulators of adipocyte differentiation through the inhibitory phosphorylation of Peroxisome proliferator-activated receptor (PPAR) γ. Together, these results demonstrate gene- and tissue-specific roles for the Mat1 subunit of TFIIH and open up new therapeutic possibilities in the treatment of diseases such as type II diabetes, hepatosteatosis and obesity.

Involvement of cytoskeletal structures in nerve-growth-factor-mediated induction of ornithine decarboxylase.

Induction of ornithine decarboxylase elicited in response to nerve-growth factor in target organs is greatly decreased by preincubation of these tissues with cytoskeletal poisons such as vinblastine, diamide, cytochalasin B and colchicine. These results are interpreted as evidence for the involvement of receptor-associated cytoskeletal structures in mediating the nerve-growth-factor-specific induction of ornithine decarboxylase.

Involvement of cytoskeletal structures in nerve-growth-factor-mediated induction of ornithine decarboxylase

Induction of ornithine decarboxylase elicited in response to nerve-growth factor in target organs is greatly decreased by preincubation of these tissues with cytoskeletal poisons such as vinblastine, diamide, cytochalasin B and colchicine. These results are interpreted as evidence for the involvement of receptor-associated cytoskeletal structures in mediating the nerve-growth-factor-specific induction of ornithine decarboxylase.

The German Military Entrepreneur Ernst von Mansfeld and His Conduct of Asymmetrical Warfare in the Thirty Years War

The dissertation examines aspects of asymmetrical warfare in the war-making of the German military entrepreneur Ernst von Mansfeld during his involvement in the Thirty Years War. Due to the nature of the inquiry, which combines history with military-political theory, the methodological approach of the dissertation is interdisciplinary. The theoretical framework used is that of asymmetrical warfare. The primary sources used in the dissertation are mostly political pamphlets and newsletters. Other sources include letters, documents, and contemporaneous chronicles. The secondary sources are divided into two categories, literature on the history of the Thirty Years War and textbooks covering the theory of asymmetrical warfare. The first category includes biographical works on Ernst von Mansfeld, as well as general histories of the Thirty Years War and seventeenth-century warfare. The second category combines military theory and political science. The structure of the dissertation consists of eight lead chapters, including an introduction and conclusion. The introduction covers the theoretical approach and aims of the dissertation, and provides a brief overlook of the sources and previous research on Ernst von Mansfeld and asymmetrical warfare in the Thirty Years War. The second chapter covers aspects of Mansfeld s asymmetrical warfare from the perspective of operational art. The third chapter investigates the illegal and immoral aspects of Mansfeld s war-making. The fourth chapter compares the differing methods by which Mansfeld and his enemies raised and financed their armies. The fifth chapter investigates Mansfeld s involvement in indirect warfare. The sixth chapter presents Mansfeld as an object and an agent of image and information war. The seventh chapter looks into the counter-reactions, which Mansfeld s asymmetrical warfare provoked from his enemies. The eighth chapter offers a conclusion of the findings. The dissertation argues that asymmetrical warfare presented itself in all the aforementioned areas of Mansfeld s conduct during the Thirty Years War. The operational asymmetry arose from the freedom of movement that Mansfeld enjoyed, while his enemies were constrained by the limits of positional warfare. As a non-state operator Mansfeld was also free to flout the rules of seventeenth-century warfare, which his enemies could not do with equal ease. The raising and financing of military forces was another source of asymmetry, because the nature of early seventeenth-century warfare favoured private military entrepreneurs rather than embryonic fiscal-military states. The dissertation also argues that other powers fought their own asymmetrical and indirect wars against the Habsburgs through Mansfeld s agency. Image and information were asymmetrical weapons, which were both aimed against Mansfeld and utilized by him. Finally, Mansfeld s asymmetrical threat forced the Habsburgs to adapt to his methods, which ultimately lead to the formation of a subcontracted Imperial Army under the management and leadership of Albrecht von Wallenstein. Therefore Mansfeld s asymmetrical warfare ultimately paved way for the kind of state-monopolized, organised, and symmetrical warfare that has prevailed from 1648 onwards. The conclusion is that Mansfeld s conduct in the Thirty Years War matched the criteria for asymmetrical warfare. While traditional historiography treated Mansfeld as an anomaly in the age of European state formation, his asymmetrical warfare has begun to bear resemblance to the contemporary conflicts, where nation states no longer hold the monopoly of violence.

Dynamic Structure Factor of Sponge Phases

We predict the dynamic light scattering intensity S(q,t) for the L3 phase (anomalous isotropic phase) of dilute surfactant solutions. Our results are based on a Landau-Ginzburg approach, which was previously used to explain the observed static structure factor S(q, 0). In the extreme limit of small q, we find a monoexponential decay with marginal or irrelevant hydrodynamic interactions. In most other regimes the decay of S(q,t) is strongly nonexponential; in one case, it is purely algebraic at long times.

Cycloheximide enhances factor binding to the native 40S ribosomal subunit of Microsporum canis

Native and derived ribosomal particles from the mycelial cells of Microsporum canis grown in the presence and absence of cycloheximide were compared by CsCl equilibrium density gradient centrifugation. Since the buoyant densities of ribonucleoprotein complexes are dependent on the protein-RNA ratio, they reflect the composition of these particles. The native monosomes from cells grown in the presence and absence of cycloheximide had a buoyant density of 1.585 g/cc. The native 60S subunits showed a density of 1.540 g/cc from cells grown in both presence and absence of cycloheximide, while the derived subunits showed a density of 1.610 g/cc. The derived 40S subunits had a density of 1.550 g/cc while the native 40S showed a major species of density 1.535 g/cc with three other minor species ranging in densities from 1.450-1.390 g/cc. The mycelia grown in the presence of cycloheximide showed an increased proportion of native 40S subunits in the density range of 1.450-1.390 g/cc, indicating that the drug enhances factor binding to native ribosomal subunits in M. canis.

"Die Barbaren werden von Russen gespielt" : Etniset hahmot Wladimir Kaminerin kertomuskokoelmissa "Russendisko" ja "Mein deutsches Dschungelbuch"

Pro gradu -tutkielmassani tarkastelen hahmojen etnisyyttä Wladimir Kaminerin kahdessa kertomuskokoelmassa. Kaminerin, saksalaistuneen venäjänjuutalaisen, esikoisteos Russendisko kuvaa kertojan kotiutumista itäiseen Berliiniin sekä värikästä arkea monikulttuurisessa pääkaupungissa. Mein deutsches Dschungelbuchissa Kaminer matkustaa ympäri Saksaa esittämässä tekstejään ja kirjoittaa havainnoistaan kirjaa. Vitsikkään tyylin lisäksi kokoelmien kertomuksia yhdistävänä tekijänä toimii autobiografisia piirteitä omaava kertojahahmo, yleensä nimettyjä etnisyyksiä edustavien ja ohueksi jäävien sivuhenkilöiden tullessa ja mennessä. Näistä piirteistä nousevat tutkielmani kaksi näkökulmaa etnisyyteen: tutkin, miten etnisyys suhteutuu ensinnäkin kertojahahmoon ja toiseksi eri ihmisryhmien stereotyyppiseen esittämiseen. Tutkielmani lähtökohtana on käsitys etnisyydestä – kuulumisesta johonkin kansaan tai heimoon – luonnollisen sijasta kulttuurisesti konstruoituna ilmiönä. Kertojahahmon etnisyyden tutkimisessa hyödynnän hybridin käsitettä, jolla viitataan selvärajaisten etnisyyksien sijaan niiden sekoittumiseen. Kertojahahmon juutalaisuus paljastuu useiden diskurssien jännitteiseksi risteyspaikaksi: kertojahahmo vastustaa pyrkimyksiä kiinnittää itseään uskonnollisesti ja kulttuurisesti rajattuun etniseen kompleksiin, mutta yhdistyy kaupunkielämästä inspiraationsa löytävänä individualistisena intellektuellina urbaanin juutalaiskirjallisuuden traditioon. Kertojahahmon etnisyyden ulottuvuuksista korostuu teksteissä selkeimmin venäläisyys, joka osoittautuu tietoisen performatiiviseksi ja saksalaisille suunnatuksi. Kielellisesti assimiloituneen mutta venäläisenä esiintyvän kertojahahmon asema useampien etnisyyksien kartoittamattomassa välitilassa avaa mahdollisuuden pinttyneiden etnisten vastakkainasetteluiden kritiikille. Kertojahahmo sijoittaa itsensä intertekstuaaliseen tilaan tavalla, joka kyseenalaistaa korkeakulttuuristen kaanonien lisäksi ajatuksen puhtaista kansallisista kirjallisuuksista. Relevantiksi kehykseksi Kaminerin tekstien tulkinnassa osoittautuukin transeurooppalainen pikareski-genre, jonka veijarisankareita naiivin ulkopuolisuutensa satiirin palvelukseen valjastava kertojahahmo läheisesti muistuttaa. Kertojahahmon hybridi etnisyys on yhteydessä myös siihen, miten tekstien oletetaan esittävän ja edustavan erilaisia ihmisryhmiä: se mahdollistaa hankalienkin teemojen häpeilemättömän käsittelyn. Etnisiä stereotypioita – etnistä ryhmää koskevia pinttyneitä representaatioita, joihin ihmiset turvautuvat pyrkiessään selittämään tai hallitsemaan toisia – tarkastelen imagologian ja kriittisen kulttuurintutkimuksen välinein. Etniset stereotypiat ovatkin keskeisiä Kaminerin rakentaessa lukuisia sivuhenkilöitään, jotka pelkistyvät useimmiten litteiksi, jopa karikatyyrinomaisiksi etnisyyksiensä edustajiksi. Kaminerin tekstit kiertyvät kuitenkin myös samaisten etnisten stereotypioiden satiiriksi. Yhtäältä ironian kohteena on stereotyypittelyn prosessi, jossa toisen määrittely essentialistisin termein ja yleistyksien kautta johtaa absurdeihinkin virhetulkintoihin. Toisaalta kertojahahmon toteava kuvailutapa paljastaa etnisten stereotypioiden haitalliset yhteiskunnalliset vaikutukset. Kaminerin satiirin terä kohdistuu kantasaksalaisiin, jotka näkevät muut etnisyydet pitkälti omia tarpeitaan, pelkojaan ja fantasioitaan palvelevien stereotypioiden kautta. Tutkielmani kuitenkin osoittaa, että maahanmuuttajataustaiset henkilöhahmot kykenevät myös tuotteistamaan etnisiä stereotypioita – toki ahtaissa, yhteiskunnallisten valtarakenteiden määrittämissä rajoissa. Olennaista on etnisiin stereotypioihin sisältyvä kaksiteräisyys: sama ennakko-oletusten kimppu saatetaan yhteydestä riippuen esittää ja tulkita joko negatiiviseksi tai positiiviseksi. Kaminerin tekstit tarjoavat huumorin kautta luvallisen kanavan käsitellä ja purkaa etnisyyden akseleilla liikkuvia odotuksia, pelkoja ja aggressioita, jotka ovat pitkään olleet lähes tabuja saksalaisessa yhteiskunnassa. Samalla Kaminerin tekstit puhuvat sellaisen maailman puolesta, jossa etnisyys pikemminkin mahdollistaisi kuin sitoisi inhimillistä vuorovaikutusta.

Snapthrough instability of a stochastic a von Mises truss

A von Mises truss with stochastically varying material properties is investigated for snapthrough instability. The variability of the snap-through load is calculated analytically as a function of the material property variability represented as a stochastic process. The bounds are established which are independent of the knowledge of the complete description of correlation structure which is seldom possible using the experimental data. Two processes are considered to represent the material property variability and the results are presented graphically. Ein von Mises Fachwerk mit stochastisch verteilten Materialeigenschaften wird bezüglich der Durchschlagsinstabilität untersucht. Die Spannbreite der Durchschlagslast wird analytisch als Funktion der Spannbreite der Materialeigenschaften berechnet, die stochastisch verteilt angenommen werden. Eine explizite Gesamtbeschreibung der Struktur ist bei Benutzung experimenteller Daten selten möglich. Deshalb werden Grenzen für die Durchschlagskraft entwickelt, die von der Kenntnis dieser Gesamtbeschreibung unabhängig sind. Zwei Grenzfälle werden betrachtet, um die Spannbreite der Materialeigenschaften darzustellen. Die Ergebnisse werden grafisch dargestellt.

A discrete state perspective of manipulator workspaces Vorstellungen von diskreten zuständen von manipulator-arbeitsräumen

The finite resolution of joint drives or sensors imparts a discrete nature to the joints of a manipulator. Because of this an arbitrary point in the workspace cannot be reached without error even in ideal mechanical environment. This paper investigates the effect of this discrete nature of the joints on the accuracy of performance of a manipulator and develops a method to select the joint states to reach a point with least error. It is shown that the configuration leading to least error cannot, in general, be found from configuration space, especially when there is large variation in the link lengths or joint resolutions or both. The anomaly becomes severe when the gross motion of the end-effector approaches the local resolution of the workspace. The paper also shows how to distinguish two workspaces which may be identical so far as the boundary points are concerned, taking the joint resolutions into account. Finally, the concepts have been extended to define continuous space global and local performance indices for general multi degree of freedom manipulators.

Higher twist and higher order contributions to the pion electromagnetic form factor

The O(m(pi)4/(m(u) + (d))2Q2) and O(alpha(S)2) corrections to the leading term of the perturbative QCD calculation of the pion electromagnetic form factor are examined numerically. Both sets of terms provide significant corrections for values of Q2 between 1 and 15 GeV2/c2.

Implications of the recent high statistics determination of the pion electromagnetic form factor in the timelike region

The recently evaluated two-pion contribution to the muon g - 2 and the phase of the pion electromagnetic form factor in the elastic region, known from pi pi scattering by Fermi-Watson theorem, are exploited by analytic techniques for finding correlations between the coefficients of the Taylor expansion at t = 0 and the values of the form factor at several points in the spacelike region. We do not use specific parametrizations, and the results are fully independent of the unknown phase in the inelastic region. Using for instance, from recent determinations, < r(pi)(2)> = (0.435 +/- 0.005) fm(2) and F(-1.6 GeV2) = 0.243(-0.014)(+0.022), we obtain the allowed ranges 3.75 GeV-4 less than or similar to c less than or similar to 3.98 GeV-4 and 9.91 GeV-6 less than or similar to d less than or similar to 10.46 GeV-6 for the curvature and the next Taylor coefficient, with a strong correlation between them. We also predict a large region in the complex plane where the form factor cannot have zeros.

Molecular organization of the gene encoding Xenopus laevis transforming growth factor-beta 5

Transforming growth factor-beta s (TGF-beta 5) are multifunctional polypeptides, known to influence proliferation and differentiation of many cell types. TGF-beta 5 cDNA was cloned from Xenopus laevis and this isoform is unique to the amphibians. Here, we report the isolation and characterization of the TGF-beta 5 genomic clones to determine the structure of TGF-beta 5 gene. The gene consists of seven exons and all intron-exon boundaries follow the GT-AG consensus. The organization of TGF-beta 5 gene was identical to that of the mammalian TGF-beta isoforms, with the exception of position of the first splice junction. We determined the size of TGF-beta 5 gene to be approximately 20 kb.

Isolation of transforming growth factor-beta 2 cDNA from a fish, Cyprinus carpio by RT-PCR

Transforming Growth Factors-beta (TGF-beta s) have been described in many vertebrate species of amphibians, aves and mammals. In this report we demonstrate the presence of TGF-beta 2 in pisces. TGF-beta 2 has been cloned from a fish, Cyrinus carpio, by RT-PCR using degenerate oligonucleotide primers. Sequence analysis of the amplified product and alignment of the deduced amino acid sequence with the human TGF-beta 2 amino acid sequence revealed 81% and 93% identity in the precursor and the mature regions, respectively. The northern blot analysis of fish heart RNA shows a major messenger RNA species of about 8.0 kb and two messages of very low abundance of about 5.0 kb and 4.0 kb. The identification of TGF-beta 2 isoform in Pisces and it's high degree of homology with the mammalian isoform suggests that among all TGF-beta isoforms, TGF-beta 2 is the most conserved during evolution. (C) 1997 Elsevier Science B.V.