Sphingosine Kinases in B-lineage Acute Lymphoblastic Leukaemia

The work presented in this thesis examines firstly, the effects of the sphingosine like immunomodulatory drug FTY720 on B-lineage acute lymphoblastic leukaemia (ALL) cells. Secondly, the research focuses on a related area, namely, the intra-cellular enzymes called sphingosine kinases (SphKs). FTY720 resulted in cytotoxic effects and the induction of autophagy, in vitro in ALL cells. However, disparate in vivo effects were seen in Ph+ and Ph- ALL with a reduction in disease burden seen only in the former, highlighting the importance of pharmacological testing in both in vitro and in vivo settings. Sphingosine kinase 1 (SphK1) and sphingosine kinase 2 (SphK2) are over-expressed in ALL with inhibition producing cytotoxic effects, autophagy and predominantly caspase-independent cell death. SphK1 and SphK2 gene deletion resulted in reduced leukaemia penetrance in a murine Ph+ ALL disease model and SphK2 inhibition reduced the growth of human ALL xenografts. SphK2 inhibition resulted in lower MYC gene and protein expression through reduced association of acetylated histone H3 with the MYC promoter. This establishes a completely novel insight into the interactions of SphK2 in ALL and signifies the importance of sphingolipid signalling in this aggressive malignancy

Development of the thermal denitration in-storage-can step in the CEUSP process

A thermal denitration in-the-storage-can process has been developed for use in the Consolidated Edison Uranium Solidification Program Facility. This process is being used to convert approx.1000 kg of highly fissile and radioactive uranium to a solid form for safe long-term storage. The material being solidified also contains approx.300 kg of cadmium and approx.40 kg of gadolinium which had been combined with the uranium to provide criticality safety. The unique thermal denitration process was found to be extremely susceptible to entrainment of solids by splattering, foaming, or expulsion actions. The process connection nozzle, through which the feed solution and purging air are supplied and the emerging off-gases are discharged, and the off-gas handling system were modified extensively to permit operation without development of nozzle or line pluggage due to accumulation of solid deposits. A process study was made to determine the effects of feed components and process variables on the tendency of the reacting mixture to splatter, foam, or be expelled. Because of the equipment modifications and the selection of appropriate processing conditions, the feed material is being denitrated without significant problems

Is eenvoudig beter? : Twee essays over natuur en landschap in het nieuwe omgevingsbeleid

This report includes two essays on the foundations of planning and environmental policy, focusing on natureand landscape. At a time when policy is changing, it is important to reflect on the foundations of thesepolicies, specifically on the question ‘What wisdom in caring for the environment?’ To reflect on this questionthe thinking of pioneers of regional planning, nature conservation and landscape management is linked withthat of a number of contemporary philosophers. The resulting proposal to consider environmental care as an‘anhropo-technique’, for which societal learning is crucial, implies a curbing of the standard thinking and aclear definition of the public interest, also at the national level. The second essay argues for a better use ofspatial planning policy to support objectives for nature and the landscape. Besides the Environment andPlanning Act, this should include the development and deployment of ‘policy arrangements’ that reflectvarious perspectives on nature and landscape---Dit rapport bevat twee essays over de grondslagen voor het omgevingsbeleid toegespitst op natuur enlandschap. In een periode waarin het beleid voor de omgeving sterk verandert, is het belangrijk om tereflecteren op de grondslagen van dit beleid. Wat is wijsheid in de zorg voor de omgeving? Daartoe wordt inhet eerste essay het denken van pioniers van de ruimtelijke ordening, het natuurbeheer en hetlandschapsonderhoud gerelateerd aan een aantal hedendaagse filosofen. Dit leidt tot het voorstel om deomgevingszorg te zien als een antropotechniek waarin maatschappelijke oefening centraal staat. Ditimpliceert onder meer een beperking van het norm-denken en een heldere definitie van het publieke belang,ook op nationaal niveau. Het tweede essay bepleit om het ruimtelijk beleid beter in te zetten voor natuur- enlandschapsopgaven. Het gaat daarbij naast de Omgevingswet om het ontwikkelen en benutten vanruimtelijke beleidsarrangementen die aansluiten bij verschillende kijkrichtingen naar natuur en landscha

The complex superstructure in Mg1-xAlxB2 at x~0.5

Electron diffraction and high resolution microscopy have been performed on Mg1-xAlxB2 with x~0.5. This composition displays a superstructure with a repeat period of exactly 2c along the c axis and about 10 nm in the a-b plane. The superstructure results in ring-shaped superreflections in the diffraction pattern. Irradiation by a strong electron beam results in a loss of the superstructure and a decrease of about 1% in the c lattice parameter. In-situ heating and cooling on the other hand showed that the superstructure is stable from 100 K to 700 K. Possible origins for the superstructure are proposed

Zeeman effects on the impurity-induced resonances in d-wave superconductors

It is shown how the resonant states induced by a single spinless impurity in a d-wave superconductor evolve under the effect of an applied Zeeman magnetic field. Moreover, it is demonstrated that the spin-orbit coupling to the impurity potential can have important and characteristic effects on the resonant states and their response to the Zeeman field, especially when the impurity is close to the unitary limit. For zero or very small spin-orbit interaction, the resonant states becomes Zeeman splitted by the magnetic field while when the spin-orbit coupling is important, new low-lying resonances arise which do not show any Zeeman splitting.Comment: 5 pages with 5 eps figures embedded. To appear on Phys. Rev.

Quantized Skyrmion Fields in 2+1 Dimensions

A fully quantized field theory is developped for the skyrmion topological excitations of the O(3) symmetric CP$^1$-Nonlinear Sigma Model in 2+1D. The method allows for the obtainment of arbitrary correlation functions of quantum skyrmion fields. The two-point function is evaluated in three different situations: a) the pure theory; b) the case when it is coupled to fermions which are otherwise non-interacting and c) the case when an electromagnetic interaction among the fermions is introduced. The quantum skyrmion mass is explicitly obtained in each case from the large distance behavior of the two-point function and the skyrmion statistics is inferred from an analysis of the phase of this function. The ratio between the quantum and classical skyrmion masses is obtained, confirming the tendency, observed in semiclassical calculations, that quantum effects will decrease the skyrmion mass. A brief discussion of asymptotic skyrmion states, based on the short distance behavior of the two-point function, is also presented.Comment: Accepted for Physical Review

Evaluatie landinrichtingsinstrumentarium Wet inrichting landelijk gebied

Deze beleids- en wetsevaluatie van de landinrichtingsregels uit de Wet inrichting landelijk gebied toont dat inzet van het landinrichtingsinstrumentarium voor doorzettingsmacht zorgt bij de aanpak van meervoudige inrichtingsopgaven in het landelijk gebied. Doorzettingsmacht alleen is hiervoor echter niet voldoende. Om succes te hebben moeten gebiedspartijen ervan overtuigd zijn dat landinrichting nodig is en zich mede-eigenaar voelen van het proces. De meerwaarde van landinrichting ten opzichte van integrale vrijwillige gebiedsprocessen bestaat uit meer zekerheid over doelbereik voor de overheid, realisatie van een optimale verkaveling, meer rechtszekerheid voor belanghebbenden en de mogelijkheid om meerdere verwervingsinstrumenten in te zetten. Ondanks deze voordelen is het aantal landinrichtingsprojecten de afgelopen decennia gestaag afgenomen. Veel provincies associëren landinrichting met langdurige en ingewikkelde processen en/of vinden het instrumentarium niet passen bij de aard van de huidige opgaven. Verder schrikken zij vaak terug voor het dwingende karakter van landinrichting. Wijzigingen in de Wilg en recente procesvernieuwingen hebben aan deze beeldvorming weinig veranderd

Superconductivity from correlated hopping

We consider a chain described by a next-nearest-neighbor hopping combined with a nearest-neighbor spin flip. In two dimensions this three-body term arises from a mapping of the three-band Hubbard model for CuO$_2$ planes to a generalized $t-J$ model and for large O-O hopping favors resonance-valence-bond superconductivity of predominantly $d$-wave symmetry. Solving the ground state and low-energy excitations by analytical and numerical methods we find that the chain is a Luther-Emery liquid with correlation exponent $K_{\rho} = (2-n)^2/2$, where $n$ is the particle density.Comment: 10 pages, RevTeX 3.0 + 2 PostScript figs. Accepted for publication in Phys.Rev.

Influence of next-nearest-neighbor electron hopping on the static and dynamical properties of the 2D Hubbard model

Comparing experimental data for high temperature cuprate superconductors with numerical results for electronic models, it is becoming apparent that a hopping along the plaquette diagonals has to be included to obtain a quantitative agreement. According to recent estimations the value of the diagonal hopping $t'$ appears to be material dependent. However, the values for $t'$ discussed in the literature were obtained comparing theoretical results in the weak coupling limit with experimental photoemission data and band structure calculations. The goal of this paper is to study how $t'$ gets renormalized as the interaction between electrons, $U$, increases. For this purpose, the effect of adding a bare diagonal hopping $t'$ to the fully interacting two dimensional Hubbard model Hamiltonian is investigated using numerical techniques. Positive and negative values of $t'$ are analyzed. Spin-spin correlations, $n(\bf{k})$, $\langle n\rangle$ vs $\mu$, and local magnetic moments are studied for values of $U/t$ ranging from 0 to 6, and as a function of the electronic density. The influence of the diagonal hopping in the spectral function $A(\bf{k},\omega)$ is also discussed, and the changes in the gap present in the density of states at half-filling are studied. We introduce a new criterion to determine probable locations of Fermi surfaces at zero temperature from $n(\bf{k})$ data obtained at finite temperature. It appears that hole pockets at ${\bf{k}}=(\pi/2,\pi/2)$ may be induced for negative $t'$ while a positive $t'$ produces similar features at ${\bf{k}}=(\pi,0)$ and $(0,\pi)$. Comparisons with the standard 2D Hubbard ($t'=0$) model indicate that a negative $t'$ hopping amplitude appears to be dynamically generated. In general, we conclude that it is very dangerous to extract a bare parameter of the Hamiltonian $(t')$ from PES data whereComment: 9 pages (RevTex 3.0), 12 figures (postscript), files packed with uufile

Theory of c-axis Josephson tunneling in d-wave superconductors

The temperature and angular dependence of the c-axis Josephson current and the superfluid density in layered d-wave superconductors are studied within the framework of an extended Ambegaokar-Baratoff formalism. In particular, the effects of angle-dependent tunneling matrix elements and Andreev scattering at grain boundaries are taken into account. These lead to strong corrections of the low-temperature behavior of the plasma frequency and the Josephson current. Recent c-axis measurements on the cuprate high-temperature superconductors HgBa_2CaCu_{1+\delta} and Bi_2Sr_2CaCu_2O_{8+\delta} can therefore be interpreted to be consistent with a d-wave order parameter.Comment: Revtex, 4 pages with 4 eps figures, to appear in PRB R