Die vorliegende Arbeit 'Naturrisiken und Vorsorge. Eine systemtheoretische Beobachtung von Hangrutschungsrisiken und staatlichen Vorsorgemaßnahmen' hat das Ziel die Gestaltung und Umsetzung staatlicher Vorsorge gegenüber ...

Die Genfamilie der Maus Ceramidsynthase besteht aus sechs Mitgliedern, CerS1-CerS6, die für gewebespezifische und Fettsäureacyl-CoA abhängige Ceramidsynthasen kodieren. Im Rahmen dieser Doktorarbeit sollte die Charakterisierung ...

Aim: The present study aimed at evaluating the integration of the pharmacist in multiprofessional cancer care. <br /> Methods: Part I: Two pharmaceutical care services for cancer patients were compared. One was provided ...

Die Helikase RIG-I spielt als zytosolischer Immunrezeptor eine zentrale Rolle bei der Abwehr der meisten hoch pathogenen RNA-Viren. RIG-I erkennt 5’triphosphorylierte doppelsträngige RNA (3P-dsRNA), wie sie bei der Replikation von Viren entsteht und initiiert durch Ausschüttung von Typ I Interferonen und Chemokinen eine antivirale Immunantwort. Bisherige Publikationen fokussierten lediglich die Struktur des RIG-I Liganden. Basierend auf kristallographischen Studien wurden mit 3P-dsRNA interagierende Aminosäuren der RIG-I–RNA-Bindedomäne (RD) identifiziert und deren biologische Relevanz in dieser Arbeit durch Mutationsanalysen evaluiert. Es konnte gezeigt werden, dass die Bindung von α- und β-Phosphat durch jeweils 2 basische Aminosäuren essentiell ist, wobei die Erkennung des γ-Phosphates lediglich für die RIG-I-Aktivierung bei niedrigen Ligandenkonzentrationen notwendig wird. Als zusätzlich obligatorische Kontakte für RIG-I-Aktivierung ergaben sich die Stacking-Interaktion einer aromatischen Aminosäure mit dem 5’ basengepaarten RNA-Terminus und die Bindung eines Internukleotidphosphates des RNA-Rückgrates.<br /> In der Kristallstudie konnte zusätzlich die hoch konservierte mit 3P-dsRNA interagierende Aminosäure His830 identifiziert werden. Ihr konnte eine immunregulatorische Rolle zugeordnet werden: endogene mRNA besitzt an ihrem 5’-Ende ein Triphosphat, das durch ein ^m7G-Cap modifiziert ist. Es konnte gezeigt werden, dass nicht, wie bisher angenommen, das ^m7G-Cap allein, sondern erst die für Vertebraten charakteristische 2’-OCH₃-Gruppe am ersten Ribonukleotid (N₁) endogene RNA immunologisch inert macht. Diese Immuntoleranz von endogener RNA mit 2’-OCH₃-Gruppe an N₁ wird durch His830 vermittelt, dessen sperrige Seitenkette die Interaktion 2’-modifizierter RNA mit RIG-I inhibiert. Untersuchungen an Gelbfieber-Virus ergaben, dass auch Viren diesen Mechanismus nutzen: verlieren sie die Kompetenz zur N₁-2’-O-Methylierung, so erschwert dies kaum die Virusreplikation sondern resultiert in einer verstärkten RIG-I-abhängigen Immunantwort.<br /> Insgesamt konnten in dieser Arbeit damit sowohl neue Erkenntnisse in der RIG-I-Liganden-Interaktion auf struktureller Ebene erlangt, als auch ein neuer Toleranzmechanismus von RIG-I für endogene RNAs aufgedeckt werden. Zudem konnte geklärt werden, dass eine RIG-I-Aktivierung auch ohne Triphosphorylierung möglich ist, dabei aber niedrig affin abläuft und eine Sequenzspezifität auftritt. Diese neuen Erkenntnisse zusammen können in Zukunft genutzt werden um ein Molekül zu entwickeln, das eine gezielte kurativ Immunantwort in verschiedenen Tumorentitäten initiiert....

So far experimentally not ruled out, the stealthy Higgs scenario proposes a hidden scalar sector, to which only the Higgs has non-vanishing and possibly large couplings. Due to decays into the scalars the Higgs acquires a ...

Ziel der vorliegenden Arbeit war es, mit Schmelzextrusion und einem in der Pharmazie neuartigen Schmelzgranulationsverfahren kontinuierlich sphärische wirkstoffhaltige Pellets auf Polysaccharidbasis herzustellen.<br /> Die ...

In this thesis, the crystal chemistry of anhydrous transition metal phosphates have been extended by the syntheses of a large number of molybdenum and rhenium phosphates, (Mo^VO)₄(P₂O₇)₃, Phase X1 (a new polymorph of (Mo^VO)₄(P₂O₇)₃), <i> β</i>_I-Mo^VO(PO₄), Re^V₂O₃(P₂O₇), Re^VI₂O₃(PO₄)₂, Re^VIIO₂(PO₄), NaRe^IV₂(PO₄)₃, Re^IV₃[Si^t₂O(PO₄)₆], and (Re^VII₂O₅)Si^o₂[Si^t₂O(PO₄)₆].Crystal structures and the bonding phenomena of these new phosphates have been studied by X-ray single-crystal and spectroscopic investigations.<br /> (Mo^VO)₄(P₂O₇)₃, Phase X1 and <i> β</i>_I-Mo^VO(PO₄) were synthesized reducing Mo^VI₂P₂O₁₁ by red phosphorus followed by chemical vapour transport (CVT) using I₂ as transport agent. The formations of these molybdenyl(V) phosphates are rather sensitive to the choice of starting solids and other experimental conditions. The crystal structure of (Mo^VO)₄(P₂O₇)₃ can be derived from the SiP₂O₇ structure type according to the scheme (Mo^VO)₄(P₂O₇)₃ = 4<i>M</i>^IVP₂O₇ - “P₂O₃”. Pyrophosphates <i>M</i>P₂O₇ are structurally related to the rock salt type via the pyrite structure type. Thus, a very complicated structure can be derived from a rather simple one according to the relationship NaCl → FeS₂ → <i>M</i>^IVP₂O₇ (<i>Z</i> = 4, <i>a</i> ≈ 8 Å) → (Mo^VO)₄(P₂O₇)₃ (<i>Z</i> = 36, <i>a</i> ≈ 24, <i>b</i> ≈ 24, <i>c</i> ≈ 32 Å). As a consequence, the crystal structure of (MoO)₄(P₂O₇)₃ is considered as a hybrid of non-defect like <i>M</i>^IVP₂O₇ layer (A) and P₂O₃ deficient layer (B), built up by alternating stacking forming ABA΄B΄AB…. along the crystallographic <i>c</i>-axis. The crystal structure of <i> β</i>_I-Mo^VO(PO₄) is isotypic to β-V^VO(PO₄).<br /> α-(Mo^VIO₂)₂P₂O₇, one of the four polymorphs, was crystallized by CVT using H₂O as transport agent. Its structure has been solved from X-ray single-crystal data that showed improved precision in bond-lengths and -angles in compare to that of <b>Lister</b> <i>et al.</i> obtained from X-ray powder diffraction.<br /> The ternary phase diagram of Re / P / O has been developed at 800 and 500^oC. It shows that the redox behaviour of rhenium phosphates is considerably different from higher to lower temperatures. Our study shows that CVT are particularly suitable for the crystallization of rhenium phosphates. High volatility of Re₂O₇(g) and ReO₃<i>X</i>(g) (<i>X</i> = Cl, I, OH) allows crystallization of rhenium phosphates by CVT. Under perfectly dry conditions, dissociative sublimation of Re^VIIO₂(PO₄) in a temperature gradient 400 → 300°C is possible.<br /> In addition to the long known Re^IVP₂O₇, formation of the further tetravalent rhenium phosphates, NaRe^IV₂(PO₄)₃ and Re^IV₃[Si^t₂O(PO₄)₆] evidently show the significant thermal stability of this oxidation state of rhenium. NaRe^IV₂(PO₄)₃ is isotypic to <i>NASICON</i> NaZr₂^IV(PO₄)₃ and Re^IV₃[Si^t₂O(PO₄)₆] is isotypic to Si^oIV₃[Si^t₂O(PO₄)₆]. Single-crystal UV/Vis/NIR spectra for rhenium(IV) phosphates evidently show their similarity. The first spin allowed transition ⁴A_2g → ⁴T_2g is observed at <i>∆</i>_o ~ 25000 cm^-1. At about 8000-11000 cm^-1 and around 16500 cm^-1 spin-forbidden transitions ⁴A_2g → ²T_1g, ⁴A_2g → ²E_g, and ⁴A_2g → ²T_2g are observed. According to AOM, <i>B</i> ~ 550 cm^-1 and ξ~ 2500 cm^-1 are found. AOM calculations show that for rhenium(IV)-phosphates <i>d-p</i> π-interactions between the Re⁴⁺ and O^2- ions are present. The effective magnetic moment for Re^IVP₂O₇ is 3.22 μ<i>_B</i> which is close to the value 3.28 <i>μ_B</i> calculated within AOM.<br /> Re^V₂O₃(P₂O₇) is isostructural to W^V₂O₃(P₂O₇). Its crystal structure consists of octahedra [ReO_3/1O_3/2] which are linked via three oxygen atoms to form chain-ladder type ribbons undulating along the crystallographic <i>c</i>-axis. In another approach to the crystal structure these ribbons might be considered as sections from a ReO₃-type lattice which are linked via pyrophosphate groups to give rather wide octagonal tunnels. <br /> The crystal structure of Re^VI₂O₃(PO₄)₂ consists of [Re^VI₂O₁₁] groups with two terminal (Re=O) bonds as building units besides phosphate tetrahedra. Despite the same space group and very similar lattice parameters the orthorhombic modification of W^VI₂O₃(PO₄)₂ is not immediately structurally related to Re^VI₂O₃(PO₄)₂. In contrast to molybdenyl(V) phosphates, rather low magnetic moment for Re⁶⁺ in Re^VI₂O₃(PO₄)₂(0.07 ≤ µ_exp/<i>µ</i>_B≤ 0.38; 1.4 K ≤ <i>T</i> ≤ 300 K) and its strong temperature dependence are indicative for a very strong spin-orbit interaction. The electronic absorption spectra of <i>d</i>¹ systems in molybdenyl(V)- and rhenyl(VI)- phosphates are similar. <br /> Re^VIIO₂(PO₄) and (Re^VII₂O₅)Si^o₂[Si^t₂O(PO₄)₆] are the first anhydrous phosphates containing a heptavalent metal. These phosphates are stable up to 400°C. The crystal structure of Re^VIIO₂(PO₄) might be regarded as superstructure of the ReO₃ structure type, however, phosphorus is in tetragonal environment. The crystal structure of the silicophosphate, (Re^VII₂O₅)Si^o₂[Si^t₂O(PO₄)₆] consists of distorted [Re₂O₁₁] dioctahedra, [Si^IVO₆] octahedra and [Si^t₂O(PO₄)₆]^12- heteropolyanions. It is quite remarkable that the observed range of distances 1.66 ≤ <i>d</i>(Re^VII-O) ≤ 2.10 Å in the phosphates is very similar to that found in many other oxide compounds containing rhenium in oxidation states 4+, 5+, 6+ and 7+. Therefore, assignment of oxidation states for rhenium on the basis of distances <i>d</i>(Re-O) has to be treated with great care. As in several coordination compounds of Re⁷⁺ the formation of the perrhenyl cations (ReO₂)³⁺ and (Re₂O₅)⁴⁺ are observed in the phosphate and the silico-phosphate, respectively. The presence of two distinctly different types of oxygen atoms (terminal in the perrhenyl-groups and bridging between Re and P) is comparable to oxides and in particular phosphates of V⁴⁺, V⁵⁺, and Mo⁶⁺, which are all active catalysts for selective oxidation of hydrocarbons. These observations might emphasize the catalytic activity of rhenium phosphates. Chemically and crystal chemically Re^VIIO₂(PO₄) is very similar to oxide compounds of V⁴⁺, V⁵⁺ and Mo⁶⁺, thus providing support for the diagonal relation among V⁵⁺, Mo⁶⁺, and Re⁷⁺. This relation is further expressed by the closely related crystal structures of Re^VIIO₂(PO₄) and Mo^VIO₂(SO₄). There is even evidence for polymorphism in Re^VIIO₂(PO₄) as it was observed for Mo^VIO₂(SO₄). Phosphates of rhenium in the lower oxidation states +IV, +V, and +VI (Re^IVP₂O₇, Re^V₂O₃(P₂O₇), Re^VI₂O₃(PO₄)₂) are closely related to the corresponding tungsten compounds W^IVP₂O₇, W^V₂O₃(P₂O₇), and W^VI₂O₃(PO₄)₂. <br /> Finally, it might be concluded that with the syntheses of anhydrous rhenium phosphates at +IV, +V, +VI, and +VII oxidation states of rhenium, the crystal chemistry of anhydrous transition metal phosphates have been considerably extended. Our study shows that the redox behaviour of rhenium is comparable to that of its neighbour elements; i. e. molybdenum, vanadium. In addition to formation of a large number of ternary phosphates of these elements, up to now a plethora of quaternary phosphates have been synthesized and characterized. The main reason for the formation of such a large number of phosphates is the existence of various oxidation states and their stability in a phosphate matrix. Therefore, it is evident that an enormous research field for polynary rhenium phosphates have been opened by the present work....

Water is vital for live as such including a wide range of livelihood activities including domestic and productive needs. Access to adequate water supply would significantly contribute to poverty alleviation, whereas lack ...

Die Freisetzung von Überträgerstoffen (Transmittern) kann durch Rezeptoren gehemmt werden, die häufig direkt an den entsprechenden Nervenendigungen, also präsynaptisch lokalisiert sind. Prominentes Beispiel ist der ...

We identified the four-and-a-half LIM domain protein 2 (FHL2) as a novel regulator of CCL19-induced dendritic cell (DC) migration. Initiation of migration is a hallmark of DC function and plays a central role in the induction and regulation of immune responses. In vivo, DCs continuously acquire Ag in the periphery and migrate to draining LNs, under the influence of local environmental chemotactic factors like CCL19/21 or sphingosine 1-phosphate (S1P). We investigated the role of S1P- and RhoA regulated FHL2 in this process.<br /> We found reduced nuclear localization of FHL2 in mature bone marrow-derived DCs (BMDCs), compared with immature BMDCs, following stimulation with CCL19. Furthermore, in vitro-generated murine FHL2-/- BMDCs displayed a significantly increased migratory speed, directionality, and migratory persistence toward the chemokine CCL19 compared with wild-type BMDCs. Moreover, in vivo, FHL2-/- BMDCs showed increased migration toward lymphoid organs. FHL2-/- BMDCs increased the expression of S1P receptor 1, which was associated with greater Rac activation. An S1PR1 antagonist and knock-down of S1PR1 abrogated the increased migratory speed of FHL2-/- BMDCs. Our results identify FHL2 as an important novel regulator of DC migration via regulation of their sensitivity toward environmental migratory cues like S1P and CCL19....