Transforming growth factor -beta signaling through Smad3 in allergy : Studies in the mechanisms of asthma, atopic dermatitis and allergic contact reactions

Transforming growth factor β signalling through Smad3 in allergy Allergic diseases, such as atopic dermatitis, asthma, and contact dermatitis are complex diseases influenced by both genetic and environmental factors. It is still unclear why allergy and subsequent allergic disease occur in some individuals but not in others. Transforming growth factor (TGF)-β is an important immunomodulatory and fibrogenic factor that regulates cellular processes in injured and inflamed skin. TGF-β has a significant role in the regulation of the allergen-induced immune response participating in the development of allergic and asthmatic inflammation. TGF-β is known to be an immunomodulatory factor in the progression of delayed type hypersensitivity reactions and allergic contact dermatitis. TGF-β is crucial in regulating the cellular responses involved in allergy, such as differentiation, proliferation and migration. TGF-β signals are delivered from the cytoplasm to the nucleus by TGF-β signal transducers called Smads. Smad3 is a major signal transducer in TGF-β -signalling that controls the expression of target genes in the nucleus in a cell-type specific manner. The role of TGF-β-Smad3 -signalling in the immunoregulation and pathophysiology of allergic disorders is still poorly understood. In this thesis, the role of TGF-β-Smad -signalling pathway using Smad3 -deficient knock out mice in the murine models of allergic diseases; atopic dermatitis, asthma and allergic contact reactions, was examined. Smad3-pathway regulates allergen induced skin inflammation and systemic IgE antibody production in a murine model atopic dermatitis. The defect in Smad3 -signalling decreased Th2 cytokine (IL-13 and IL-5) mRNA expression in the lung, modulated allergen induced specific IgG1 response, and affected mucus production in the lung in a murine model of asthma. TGF-β / Smad3 -signalling contributed to inflammatory hypersensitivity reactions and disease progression via modulation of chemokine and cytokine expression and inflammatory cell recruitment, cell proliferation and regulation of the specific antibody response in a murine model of contact hypersensitivity. TGF-β modulates inflammatory responses - at least partly through the Smad3 pathway - but also through other compensatory, non-Smad-dependent pathways. Understanding the effects of the TGF-β signalling pathway in the immune system and in disease models can help in elucidating the multilevel effects of TGF-β. Unravelling the mechanisms of Smad3 may open new possibilities for treating and preventing allergic responses, which may lead to severe illness and loss of work ability. In the future the Smad3 signalling pathway might be a potential target in the therapy of allergic diseases.

Dynamics of Barrierless and Activated Chemical Reactions in a Dispersive Medium within the Fractional Diffusion Equation Approach

Barrierless chemical reactions have often been modeled as a Brownian motion on a one-dimensional harmonic potential energy surface with a position-dependent reaction sink or window located near the minimum of the surface. This simple (but highly successful) description leads to a nonexponential survival probability only at small to intermediate times but exponential decay in the long-time limit. However, in several reactive events involving proteins and glasses, the reactions are found to exhibit a strongly nonexponential (power law) decay kinetics even in the long time. In order to address such reactions, here, we introduce a model of barrierless chemical reaction where the motion along the reaction coordinate sustains dispersive diffusion. A complete analytical solution of the model can be obtained only in the frequency domain, but an asymptotic solution is obtained in the limit of long time. In this case, the asymptotic long-time decay of the survival probability is a power law of the Mittag−Leffler functional form. When the barrier height is increased, the decay of the survival probability still remains nonexponential, in contrast to the ordinary Brownian motion case where the rate is given by the Smoluchowski limit of the well-known Kramers' expression. Interestingly, the reaction under dispersive diffusion is shown to exhibit strong dependence on the initial state of the system, thus predicting a strong dependence on the excitation wavelength for photoisomerization reactions in a dispersive medium. The theory also predicts a fractional viscosity dependence of the rate, which is often observed in the reactions occurring in complex environments.

Inclusive values: Exploring the perspectives of pre-service teachers

Since the turn of the century there has been an increasing focus on inclusive education in Australian schools, and growing interest in understanding how the values of pre-service teachers impact on their willingness to implement inclusive principles in their future classrooms. The current qualitative study explored the values and views toward diversity and inclusion of pre-service teachers at one university in Queensland, Australia. Results showed that first and fourth year pre-service teachers held similar ideas about the values that teachers should have, and showed congruence between their own personal values and teacher values. Fourth year students who had undertaken an inclusive education minor placed greater emphasis on the importance of inclusion, and felt more confident about supporting this diversity in their future classrooms, than those fourth years who had not undertaken this minor. The findings from this study will inform future planning in preparing teachers for inclusive work in schools.

Organometallic chemistry of diphosphazanes. Part 26. Ruthenium hydride complexes of chiral and achiral diphosphazane ligands and asymmetric transfer hydrogenation reactions

The half-sandwhich ruthenium chloro complexes bearing chelated diphosphazane ligands, [(eta(5)-Cp)RuCl{kappa(2)-P,P-(RO)(2)PN(Me)P(OR)(2)}] [R = C6H3Me2-2,6] (1) and [(eta(5)-Cp*)RuCl{kappa(2)-P, P-X2PN(R)PYY'}] [R = Me, X = Y = Y' = OC6H5 (2); R = CHMe2, X-2 = C20H12O2, Y = Y' = OC6H5 (3) or OC6H4'Bu-4 (4)] have been prepared by the reaction of CpRu(PPh3)(2)Cl with (RO)(2)PN(Me)P(OR)(2) [R = C6H3Me2-2,6 (L-1)] or by the reaction of [Cp*RuCl2](n) with X2PN(R)PYY' in the presence of zinc dust. Among the four diastereomers (two enantiomeric pairs) possible for the "chiral at metal" complexes 3 and 4, only two diastereomers (one enantiomeric pair) are formed in these reactions. The complexes 1, 2, 4 and [(eta(5)-Cp)RuCl {kappa(2)-P,P-Ph2PN((S)-*CHMePh)PPhY)] [Y = Ph (5) or N2C3HMe2-3,5 (SCSPRRu)-(6)] react with NaOMe to give the corresponding hydride complexes [(eta(5) -Cp)RuH {kappa(2)-P,P-(RO)(2)PN(Me)P(OR)(2)}] (7), [(eta(5)-Cp*)RuH {kappa(2)-P,P'-X2PN(R)PY2)] [R = Me, X = Y = OC6H5 (8); R = CHMe2, X-2 = C20H12O2, Y = OC6H4'Bu-4 (9)] and [(eta(5) -Cp)RuH(kappa(2)-P, P-Ph2PN((S)-*CHMePh)PPhY)][Y =Ph (10) or N2C3HMe2-3,5 (SCSPRRu)(11a) and (SCSPSRu)-(11b)]. Only one enantiomeric pair of the hydride 9 is obtained from the chloro precursor 4 that bears sterically bulky substituents at the phosphorus centers. On the other hand, the optically pure trichiral complex 6 that bears sterically less bulky substituents at the phosphorus gives a mixture of two diastereomers (11a and 11b). Protonation of complex 7 using different acids (HX) gives a mixture of [(eta(5)- Cp)Ru(eta(2)-H-2){kappa(2)-P, P-(RO)(2)PN(Me)P(OR)(2))]X (12a) and [(eta(5)-Cp)Ru(H)(2){kappa(2)-P, P-(RO)(2)PN(Me)P(OR)(2)}]X (12b) of which 12a is the major product independent of the acid used; the dihydrogen nature of 12a is established by T, measurements and also by synthesizing the deuteride analogue 7-D followed by protonation to obtain the D-H isotopomer. Preliminary investigations on asymmetric transfer hydrogenation of 2-acetonaphthone in the presence of a series of chiral diphosphazane ligands show that diphosphazanes in which the phosphorus centers are strong pi-acceptor in character and bear sterically bulky substituents impart moderate levels of enantioselectivity. Attempts to identify the hydride intermediate involved in the asymmetric transfer hydrogenation by a model reaction suggests that a complex of the type, [Ru(H)(Cl){kappa(2)-P,P-X2PN(R)PY2)(solvent)(2)] could be the active species in this transformation. (c) 2007 Elsevier B.V. All rights reserved.

Measurement of Particle Production and Inclusive Differential Cross Sections in pbar{p} Collisions at sqrt{s}=1.96 TeV

We report a set of measurements of particle production in inelastic pbar{p} collisions collected with a minimum-bias trigger at the Tevatron Collider with the CDF II experiment. The inclusive charged particle transverse momentum differential cross section is measured, with improved precision, over a range about ten times wider than in previous measurements. The former modeling of the spectrum appears to be incompatible with the high particle momenta observed. The dependence of the charged particle transverse momentum on the event particle multiplicity is analyzed to study the various components of hadron interactions. This is one of the observable variables most poorly reproduced by the available Monte Carlo generators. A first measurement of the event transverse energy sum differential cross section is also reported. A comparison with a Pythia prediction at the hadron level is performed. The inclusive charged particle differential production cross section is fairly well reproduced only in the transverse momentum range available from previous measurements. At higher momentum the agreement is poor. The transverse energy sum is poorly reproduced over the whole spectrum. The dependence of the charged particle transverse momentum on the particle multiplicity needs the introduction of more sophisticated particle production mechanisms, such as multiple parton interactions, in order to be better explained.

Measurement of particle production and inclusive differential cross sections in pp̅ collisions at √s=1.96 TeV

We report a set of measurements of particle production in inelastic pbar{p} collisions collected with a minimum-bias trigger at the Tevatron Collider with the CDF II experiment. The inclusive charged particle transverse momentum differential cross section is measured, with improved precision, over a range about ten times wider than in previous measurements. The former modeling of the spectrum appears to be incompatible with the high particle momenta observed. The dependence of the charged particle transverse momentum on the event particle multiplicity is analyzed to study the various components of hadron interactions. This is one of the observable variables most poorly reproduced by the available Monte Carlo generators. A first measurement of the event transverse energy sum differential cross section is also reported. A comparison with a Pythia prediction at the hadron level is performed. The inclusive charged particle differential production cross section is fairly well reproduced only in the transverse momentum range available from previous measurements. At higher momentum the agreement is poor. The transverse energy sum is poorly reproduced over the whole spectrum. The dependence of the charged particle transverse momentum on the particle multiplicity needs the introduction of more sophisticated particle production mechanisms, such as multiple parton interactions, in order to be better explained.

Humanitaarisuuden varjossa : Poliittiset tekijät lastensiirroissa Ruotsiin sotiemme aikana ja niiden jälkeen

The evacuation of Finnish children to Sweden during WW II has often been called a small migration . Historical research on this subject is scarce, considering the great number of children involved. The present research has applied, apart from the traditional archive research, the framework of history-culture developed by Rüsen in order to have an all-inclusive approach to the impact of this historical event. The framework has three dimensions: political, aesthetic and cognitive. The collective memory of war children has also been discussed. The research looks for political factors involved in the evacuations during the Winter War and the Continuation War and the post-war period. The approach is wider than a purely humanitarian one. Political factors have had an impact in both Finland and Sweden, beginning from the decision-making process and ending with the discussion of the unexpected consequences of the evacuations in the Finnish Parliament in 1950. The Winter War (30.11.1939 13.3.1940) witnessed the first child transports. These were also the model for future decision making. The transports were begun on the initiative of Swedes Maja Sandler, the wife of the resigned minister of foreign affairs Rickard Sandler, and Hanna Rydh-Munck af Rosenschöld , but this activity was soon accepted by the Swedish government because the humanitarian help in the form of child transports lightened the political burden of Prime Minister Hansson, who was not willing to help Finland militarily. It was help that Finland never asked for and it was rejected at the beginning. The negative response of Minister Juho Koivisto was not taken very seriously. The political forces in Finland supporting child transports were stronger than those rejecting them. The major politicians in support belonged to Finland´s Swedish minority. In addition, close to 1 000 Finnish children remained in Sweden after the Winter War. No analysis was made of the reasons why these children did not return home. A committee set up to help Finland and Norway was established in Sweden in 1941. Its chairman was Torsten Nothin, an influential Swedish politician. In December 1941 he appealed to the Swedish government to provide help to Finnish children under the authority of The International Red Cross. This plea had no results. The delivery of great amounts of food to Finland, which was now at war with Great Britain, had automatically caused reactions among the allies against the Swedish imports through Gothenburg. This included the import of oil, which was essential for the Swedish navy and air force. Oil was later used successfully to force a reduction in commerce between Sweden and Finland. The contradiction between Sweden´s essential political interests and humanitarian help was solved in a way that did not harm the country´s vital political interests. Instead of delivering help to Finland, Finnish children were transported to Sweden through the organisations that had already been created. At the beginning of the Continuation War (25.6.1941 27.4.1945) negative opinion regarding child transports re-emerged in Finland. Karl-August Fagerholm implemented the transports in September 1941. In 1942, members of the conservative parties in the Finnish Parliament expressed their fear of losing the children to the Swedes. They suggested that Finland should withdraw from the inter-Nordic agreement, according to which the adoptions were approved by the court of the country where the child resided. This initiative failed. Paavo Virkkunen, an influential member of the conservative party Kokoomus in Finland, favoured the so-called good-father system, where help was delivered to Finland in the form of money and goods. Virkkunen was concerned about the consequences of a long stay in a Swedish family. The risk of losing the children was clear. The extreme conservative party (IKL, the Patriotic Movement of the Finnish People) wanted to alienate Finland from Sweden and bring Finland closer to Germany. Von Blücher, the German ambassador to Finland, had in his report to Berlin, mentioned the political consequences of the child transports. Among other things, they would bring Finland and Sweden closer to each other. He had also paid attention to the Nordic political orientation in Finland. He did not question or criticize the child transports. His main interest was to increase German political influence in Finland, and the Nordic political orientation was an obstacle. Fagerholm was politically ill-favoured by the Germans, because he had a strong Nordic political disposition and had criticised Germany´s activities in Norway. The criticism of child transports was at the same time criticism of Fagerholm. The official censorship organ of the Finnish government (VTL) denied the criticism of child transports in January 1942. The reasons were political. Statements made by members of the Finnish Parliament were also censored, because it was thought that they would offend the Swedes. In addition, the censorship organ used child transports as a means of active propaganda aimed at improving the relations between the two countries. The Finnish Parliament was informed in 1948 that about 15 000 Finnish children still remained in Sweden. These children would stay there permanently. In 1950 the members of the Agrarian Party in Finland stated that Finland should actively strive to get the children back. The party on the left (SKDL, the Democratic Movement of Finnish People) also focused on the unexpected consequences of the child transports. The Social Democrats, and largely Fagerholm, had been the main force in Finland behind the child transports. Members of the SKDL, controlled by Finland´s Communist Party, stated that the war time authorities were responsible for this war loss. Many of the Finnish parents could not get their children back despite repeated requests. The discussion of the problem became political, for example von Born, a member of the Swedish minority party RKP, related this problem to foreign policy by stating that the request to repatriate the Finnish children would have negative political consequences for the relations between Finland and Sweden. He emphasized expressing feelings of gratitude to the Swedes. After the war a new foreign policy was established by Prime Minister (1944 1946) and later President (1946 1956) Juho Kusti Paasikivi. The main cornerstone of this policy was to establish good relations with the Soviet Union. The other, often forgotten, cornerstone was to simultaneously establish good relations with other Nordic countries, especially Sweden, as a counterbalance. The unexpected results of the child evacuation, a Swedish initiative, had violated the good relations with Sweden. The motives of the Democratic Movement of Finnish People were much the same as those of the Patriotic Movement of Finnish People. Only the ideology was different. The Nordic political orientation was an obstacle to both parties. The position of the Democratic Movement of Finnish People was much better than that of the Patriotic Movement of Finnish People, because now one could clearly see the unexpected results, which included human tragedy for the many families who could not be re-united with their children despite their repeated requests. The Swedes questioned the figure given to the Finnish Parliament regarding the number of children permanently remaining in Sweden. This research agrees with the Swedes. In a calculation based on Swedish population registers, the number of these children is about 7 100. The reliability of this figure is increased by the fact that the child allowance programme began in Sweden in 1948. The prerequisite to have this allowance was that the child be in the Swedish population register. It was not necessary for the child to have Swedish nationality. The Finnish Parliament had false information about the number of Finnish children who remained in Sweden in 1942 and in 1950. There was no parliamentary control in Finland regarding child transports, because the decision was made by one cabinet member and speeches by MPs in the Finnish Parliament were censored, like all criticism regarding child transports to Sweden. In Great Britain parliamentary control worked better throughout the whole war, because the speeches regarding evacuation were not censored. At the beginning of the war certain members of the British Labour Party and the Welsh Nationalists were particularly outspoken about the scheme. Fagerholm does not discuss to any great extent the child transports in his memoirs. He does not evaluate the process and results as a whole. This research provides some possibilities for an evaluation of this sort. The Swedish medical reports give a clear picture of the physical condition of the Finnish children when arriving in Sweden. The transports actually revealed how bad the situation of the poorest children was. According to Titmuss, similar observations were made in Great Britain during the British evacuations. The child transports saved the lives of approximately 2 900 children. Most of these children were removed to Sweden to receive treatment for illnesses, but many among the healthy children were undernourished and some suffered from the effects of tuberculosis. The medical inspection in Finland was not thorough. If you compare the figure of 2 900 children saved and returned with the figure of about 7 100 children who remained permanently in Sweden, you may draw the conclusion that Finland as a country failed to benefit from the child transports, and that the whole operation was a political mistake with far-reaching consequenses. The basic goal of the operation was to save lives and have all the children return to Finland after the war. The difficulties with the repatriation of the children were mainly psychological. The level of child psychology in Finland at that time was low. One may question the report by Professor Martti Kaila regarding the adaptation of children to their families back in Finland. Anna Freud´s warnings concerning the difficulties that arise when child evacuees return are also valid in Finland. Freud viewed the emotional life of children in a way different from Kaila: the physical survival of a small child forces her to create strong emotional ties to the person who is looking after her. This, a characteristic of all small children, occurred with the Finnish children too, and it was something the political decision makers in Finland could not see during and after the war. It is a characteristic of all little children. Yet, such experiences were already evident during the Winter War. The best possible solution had been to limit the child transports only to children in need of medical treatment. Children from large and poor families had been helped by organising meals and by buying food from Denmark with Swedish money. Assisting Finland by all possible means should have been the basic goal of Fagerholm in September 1941, when the offer of child transports came from Sweden. Fagerholm felt gratitude towards the Swedes. The risks became clear to him only in 1943. The war children are today a rather scattered and diffuse group of people. Emotionally, part of these children remained in Sweden after the war. There is no clear collective memory, only individual memories; the collective memory of the war children has partly been shaped later through the activities of the war child associations. The main difference between the children evacuated in Finland (for example from Karelia to safer areas with their families) and the war children, who were sent abroad, is that the war children lack a shared story and experience with their families. They were outsiders . The whole matter is sensitive to many of such mothers and discussing the subject has often been avoided in families. The war-time censorship has continued in families through silence and avoidance and Finnish politicians and Finnish families had to face each other on this issue after the war. The lack of all-inclusive historical research has also prevented the formation of a collective awareness among war children returned to Finland or those remaining permanently abroad.. Knowledge of historical facts will help war-children by providing an opportunity to create an all-inclusive approach to the past. Personal experiences should be regarded as part of a large historical entity shadowed by war and where many political factors were at work in both Finland and Sweden. This means strengthening of the cognitive dimension discussed in Rüsen´s all-inclusive historical approach.

Transformation reactions of α-pinene—I : Reactions of ethyl (−)-2,2-dimethyl-3-ketocyclobutyl acetate

Some transformation reactions of α-pinene to give 4- and 3-membered ring compounds, not hitherto obtained from this source, are described. The study furnished a convenient method of preparation of the optically active cyclobutanone IVa, the title compound which served as the key substrate for all the transformations reported.

Inclusive Search for Standard Model Higgs Boson Production in the WW Decay Channel using the CDF II Detector

We present a search for standard model (SM) Higgs boson production using ppbar collision data at sqrt(s) = 1.96 TeV, collected with the CDF II detector and corresponding to an integrated luminosity of 4.8 fb-1. We search for Higgs bosons produced in all processes with a significant production rate and decaying to two W bosons. We find no evidence for SM Higgs boson production and place upper limits at the 95% confidence level on the SM production cross section (sigma(H)) for values of the Higgs boson mass (m_H) in the range from 110 to 200 GeV. These limits are the most stringent for m_H > 130 GeV and are 1.29 above the predicted value of sigma(H) for mH = 165 GeV.

Reactions with disulphur monoxide solutions obtained by the reduction of cupric oxide by elemental sulphur

When the products of reaction between elemental sulphur and copper oxide at elevated temperature in vacuum are bubbled through chilled inert organic solvents like carbontetrachloride, orange-yellow solutions were obtained indicating the presence of lower oxide of sulphur. This lower oxide has been found to be disulphur monoxide as shown by three different types of reactions; (1) Mercury decomposition, (2) Reaction with hydrogen iodide and hydrolytic reaction in an alkaline homogeneous medium.

Reactions of tetrahalogeno-1,2-benzoquinones. Part III. Reaction of tetrachloro-1,2-benzoquinone with tetralones and naphthols: Pathway to the condensates

With a view to understanding the mechanism of the formation of 6-methoxy-2,2-(tetrachloro--phenylenedioxy)-naphthalen-1 (2H)-one (IIIa) in the reaction of 6-methoxy-1-tetralone (Ia) with tetrachloro-1,2-benzoquinone (II), the reaction of (II) with various tetralones and naphthols has been studied. Reaction with either α-tetralone or α-naphthol gives 2,2-(tetrachloro-o-phenylenedioxy)naphthalen-1 (2H)-one (IIIb), whereas reaction with either β-tetralone or β-naphthol gives a mixture of (IIIb) and ,1-(tetrachloro-o-phenylenedioxy)-naphthalen-2 (1H)-one (IX), with the former predominating. Further, reactions of (II) with 7-methoxy-3,4-dihydrophenanthren- 1 (2H)-one and m-methoxyphenol gave respectively 7-methoxy- ,2-(tetrachloro-o- phenylenedioxy)phenanthren-1 (2H)-one (VII) and 3-methoxy-6,6-(tetrachloro-o- phenylenedioxy)cyclohexa-2,4-dien-1-one (VIII). Structures of all these compounds have been proved on the basis of i.r. and n.m.r. data. The pathway to the formation of the condensates (III) is discussed.

Hydrolytic reactions of tetrasulphur tetranitride in a homogeneous medium

The hydrolytic reactions of tetrasulphur tetranitride are studied in a homogeneous medium. Alkaline hydrolysis gives sulphite, thiosulphate, sulphate and sulphide whereas the products in acid hydrolysis are mainly sulphur dioxide, elemental sulphur and hydrogen sulphide, with traces of polythionates. Under optimum conditions, tetrasulphur tetranitride reacts with sulphite consuming 2 moles of sulphite per mole of sulphur nitride to give 2 moles of trithionate. The reaction of sulphur nitride with thiosulphuric acid gives pentathionate and tetrathionate.

Searching the inclusive ℓγE̸T+b-quark signature for radiative top quark decay and non-standard-model processes

In a search for new phenomena in a signature suppressed in the standard model of elementary particles (SM), we compare the inclusive production of events containing a lepton, a photon, significant transverse momentum imbalance (MET), and a jet identified as containing a b-quark, to SM predictions. The search uses data produced in proton-antiproton collisions at 1.96 TeV corresponding to 1.9 fb-1 of integrated luminosity taken with the CDF detector at the Fermilab Tevatron. We find 28 lepton+photon+MET+b events versus an expectation of 31.0+4.1/-3.5 events. If we further require events to contain at least three jets and large total transverse energy, simulations predict that the largest SM source is top-quark pair production with an additional radiated photon, ttbar+photon. In the data we observe 16 ttbar+photon candidate events versus an expectation from SM sources of 11.2+2.3/-2.1. Assuming the difference between the observed number and the predicted non-top-quark total is due to SM top quark production, we estimate the ttg cross section to be 0.15 +- 0.08 pb.

Aspects of tautomerism. Part II. Reactions of the pseudo-acid chloride of o-benzoylbenzoic acid with nucleophiles

Reactions of fourteen nucleophiles with the pseudo-acid chloride of o-benzoylbenzoic acid in two solvents have been studied. The nucleophiles that react primarily at the tetrahedral carbon atom to give pseudo derivatives, are weaker than those that react at the carbonyl carbon atom causing opening of the lactone ring. An explanation for this phenomenon is advanced.