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Tumoren konnen durch abnormes Wachstum jedweder Zellart entstehen. Benigne Tumoren wachsen lokal, wahrend maligne Tumoren („Krebs“) invasiv in umliegendes Gewebe wachsen und im gesamten Organismus Metastasen bilden konnen.

Die quantitative Analyse der Geschwindigkeit biochemischer Reaktionen ist Gegenstand der Enzymkinetik. Die Geschwindigkeit einer Reaktion hangt von der Konzentration der Substrate ab; die Reaktionsgeschwindigkeitskonstante k ist dabei unabhangig von der Substratkonzentration.

DNA-Molekule haben die Struktur einer Doppelhelix aus antiparallelen Einzelstrangen. Das Ruckgrat jedes Einzelstrangs besteht aus 2’-Desoxyribose und Phosphatresten. Vier Basen, die uber N-glykosidische Bindungen am Ruckgrat befestigt sind, halten die Einzelstrange durch komplementare Basenpaarung (Adenin mit Thymin und Guanin mit Cytosin) zusammen. In der Sequenz der Basen ist die genetische Information verschlusselt.

BACKGROUND Hypocalcaemia (HC) is the most common complication after thyroid surgery in differentiated thyroid cancer and leads to a prolongation of the hospital stay. While risk factors for HC after total thyroidectomy (TE) are well investigated, only few studies have been published about HC risk factors after completion of thyroidectomy. Our aim was to identify potential risk factors for HC after completion of TE and to compare these incidences with figures from primary total TE. MATERIALS AND METHODS A retrospective cohort study was undertaken including patients undergoing completion of TE between 2002 and 2013 in our tertiary care centre. Patients with hypocalcaemia (group 1) after undergoing second surgery were compared to normocalcaemia patients (group 2) with respect to gender, age, type of thyroid cancer, time interval between surgeries, pre/postoperative calcium and parathyroid hormone (PTH) levels, clinical hypocalcaemia signs and calcium substitution (intravenous, oral). Hypocalcaemia was defined as

This chapter proposes a new institution to remedy the EU’s current democracy protection deficit, tentatively called the ‘Copenhagen Commission’. The idea is to create an EU-specific democracy and Rule of Law watchdog, an institution which in certain respects would be comparable to the Council of Europe’s Venice Commission. Before suggesting alternatives to existing approaches, the chapter first considers what it would take for democracy and Rule of Law protection to function properly. It then seeks to specify what it would take for the EU in particular to protect liberal democracy within Member States. After expanding on the institutional setup and powers of the Copenhagen Commission, the chapter concludes by addressing a number of common objections to this proposal, as well as discussing some necessarily speculative thoughts about the conditions under which the proposal might be implemented.

The divertor solutions obtained with the plasma edge modelling tool SOLPS5.0 are discussed. The code results are benchmarked against carefully analysed L-mode discharges at various density levels with and without impurity seeding in the full-metal tokamaks ASDEX Upgrade and JET. The role of the cross-field drifts and currents in the solutions is analysed in detail, and the improvements achieved by fully activating the drift and current terms in view of matching the experimental signals are addressed. The persisting discrepancies are also discussed.

Sickness responses to lipopolysaccharide (LPS) were examined in mice with deletion of the interleukin (IL)-1 type 1 receptor (IL-1R1). IL-1R1 knockout (1(0) mice displayed intact anorexia and HPA-axis activation to intraperitoneally injected LPS (anorexia: 10 or 120 mu g/kg; HPA-axis: 120 mu g/kg), but showed attenuated but not extinguished fever (120 g/kg). Brain PGE2 synthesis was attenuated, but Cox-2 induction remained intact. Neither the tumor necrosis factor-alpha (TNF alpha) inhibitor etanercept nor the IL -6 receptor antibody tocilizumab abolished the LPS induced fever in IL -1R1 KO mice. Deletion of IL -1R1 specifically in brain endothelial cells attenuated the LPS induced fever, but only during the late, 3rd phase of fever, whereas deletion of IL-1R1 on neural cells or on peripheral nerves had little or no effect on the febrile response. We conclude that while IL-1 signaling is not critical for LPS induced anorexia or stress hormone release, IL-1R1, expressed on brain endothelial cells, contributes to the febrile response to LPS. However, also in the absence of IL-1R1, LPS evokes a febrile response, although this is attenuated. This remaining fever seems not to be mediated by IL-6 receptors or TNFa, but by some yet unidentified pyrogenic factor. Funding Agencies|Japan Society for the Promotion of Science [15K18800]; Swedish Research Council [20725, 07879]; Knut and Alice Wallenberg foundation; Swedish Brain Foundation; Swedish Cancer Foundation [213/692]; County Council of Ostergotland; Sixth Research Framework Programme of the European Union, Project MUGEN [MUGEN LSHG-CT-2005-005203]; MRC research grant [G0801296]

TGF-β is an anti-inflammatory cytokine whose signaling is negatively controlled by Smad7. Previously, we established a role for Smad7 in the generation of autoreactive T cells; however, the function of Smad7 in dendritic cells (DCs) remains elusive. Here, we demonstrate that DC-specific Smad7 deficiency resulted in elevated expression of the transcription factors Batf3 and IRF8, leading to increased frequencies of CD8(+)CD103(+) DCs in the spleen. Furthermore, Smad7-deficient DCs expressed higher levels of indoleamine 2,3-dioxygenase (IDO), an enzyme associated with tolerance induction. Mice devoid of Smad7 specifically in DCs are resistant to the development of experimental autoimmune encephalomyelitis (EAE) as a result of an increase of protective regulatory T cells (Tregs) and reduction of encephalitogenic effector T cells in the central nervous system. In agreement, inhibition of IDO activity or depletion of Tregs restored disease susceptibility. Intriguingly, when Smad7-deficient DCs also lacked the IFN-γ receptor, the mice regained susceptibility to EAE, demonstrating that IFN-γ signaling in DCs mediates their tolerogenic function. Our data indicate that Smad7 expression governs splenic DC subset differentiation and is critical for the promotion of their efficient function in immunity.

Despite different surgical patellar interventions, the decision how to treat the patella during TKA remains controversial. The purpose of this study was to quantify the effect of different reconstructive patellar interventions on patellar kinematics during TKA using optical computer navigation. We implanted ten navigated TKAs in full body specimens. During passive motion, the effect of different surgical patellar interventions on patellar kinematics was analysed. A contrarily tilt behaviour was observed in the TKA group without patellar intervention compared to the natural knee. Lateral release led to similar tilt values ( P P

Recent events in Hungary have exposed another ‘democratic deficit’ in the EU, writes Jan-Werner Muller. To defend liberal democracy throughout the Union, European institutions need more effective means of checking undemocratic behaviour among its member states than just the idle threat of suspension.

The effects of water-filtered infrared-A (wIRA) and of convective heat on viability, inflammation, inducible free radicals and antioxidative power were investigated in natural and viable skin using the ex vivo Bovine Udder System (BUS) model. Therefore, skin samples from differently treated parts of the udder of a healthy cow were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, by prostaglandin E2 (PGE2) measurement and by electron spin resonance (ESR) spectroscopy. Neither cell viability, the inflammation status, the radical status or the antioxidative defence systems of the skin were significantly affected by wIRA applied within 30 min by using an irradiance of 1900 W m(-2) which is of relevance for clinical use, but which exceeded the maximum solar IR-A irradiance at the Earth's surface more than 5 times and which resulted in a skin surface temperature of about 45 °C without cooling and of about 37 °C with convective cooling by air ventilation. No significant effects on viability and on inflammation were detected when convective heat was applied alone under equivalent conditions in terms of the resulting skin surface temperatures and exposure time. As compared with untreated skin, free radical formation was almost doubled, whereas the antioxidative power was reduced to about 50% after convective heating to about 45 °C.

Cytomegalovirus (CMV) establishes lifelong chronic infection in its host with mostly asymptomatic or only mild disease, but under immunosuppressive conditions the virus can reactivate and infection can cause life-threatening disease. CMV has evolved several mechanisms to escape from host's immunity, allowing persistence of the virus. Until now, it remains elusive whether regulatory T cells (Tregs) have an impact on insufficient host immune response against the virus in this context. In the present study, we provide evidence that CD4(+)Foxp3(+) naturally occurring Tregs (nTregs) as well as CD4(+)Foxp3(-)IL-10(+)-induced Tregs (iTregs) interfere with an effective anti-mouse CMV (mCMV) immune response. Depletion of Foxp3(+) Tregs by using DEREG mice resulted in enhanced T-cell activation as measured by the expression of CD62L, granzyme B and interferon (IFN)-γ and was associated with reduced viral titers in salivary glands, the organ where mCMV mainly persists. Moreover, we identified CD4(+)Foxp3(-) T cells to produce elevated levels of the immunosuppressive cytokine IL-10 at early time points during mCMV infection. Analysis of T-cell activation and viral replication in mCMV-infected IL-10(flox/flox) × CD4-cre mice and IL-10(flox/flox) × FIC mice revealed that T-cell-specific inactivation of IL-10, but not Foxp3(+) Treg-specific IL-10 ablation alone, resulted in elevated IFN-γ production by T cells associated with a significant decrease in viral loads in salivary glands. Thus, our data illustrate a crucial role for CD4(+)Foxp3(+) nTregs as well as IL-10-producing CD4(+)Foxp3(-) iTregs in the regulation of appropriate T-cell responses and viral clearance during mCMV infection.

We identified a suitable biomatrix that improved axon regeneration and functional outcome after partial (moderate) and complete (severe) chronic spinal cord injury (SCI) in rat. Five weeks after dorsal thoracic hemisection injury the lesion scar was resected via aspiration and the resulting cavity was filled with different biopolymers such as Matrigel™, alginate-hydrogel and polyethylene glycol 600 (PEG) all of which have not previously been used as sole graft-materials in chronic SCI. Immunohistological staining revealed marked differences between these compounds regarding axon regeneration, invasion/elongation of astrocytes, fibroblasts, endothelial and Schwann cells, revascularization, and collagen deposition. According to axon regeneration-supporting effects, the biopolymers could be ranked in the order PEG > > alginate-hydrogel > Matrigel™. Even after complete chronic transection, the PEG-bridge allowed long-distance axon regeneration through the grafted area and for, at least, 1 cm beyond the lesion/graft border. As revealed by electron microscopy, bundles of regenerating axons within the matrix area received myelin ensheathment from Schwann cells. The beneficial effects of PEG-implantation into the resection-cavity were accompanied by long-lasting significant locomotor improvement over a period of 8 months. Following complete spinal re-transection at the rostral border of the PEG-graft the locomotor recovery was aborted, suggesting a functional role of regenerated axons in the initial locomotor improvement. In conclusion, scar resection and subsequent implantation of PEG into the generated cavity leads to tissue recovery, axon regeneration, myelination and functional improvement that have not been achieved before in severe chronic SCI.

SummaryInterleukin-10 (IL-10) is a pleiotropic anti-inflammatory cytokine produced and sensed by most hematopoietic cells. Genome-wide association studies and experimental animal models point at a central role of the IL-10 axis in inflammatory bowel diseases. Here we investigated the importance of intestinal macrophage production of IL-10 and their IL-10 exposure, as well as the existence of an IL-10-based autocrine regulatory loop in the gut. Specifically, we generated mice harboring IL-10 or IL-10 receptor (IL-10Rα) mutations in intestinal lamina propria-resident chemokine receptor CX3CR1-expressing macrophages. We found macrophage-derived IL-10 dispensable for gut homeostasis and maintenance of colonic T regulatory cells. In contrast, loss of IL-10 receptor expression impaired the critical conditioning of these monocyte-derived macrophages and resulted in spontaneous development of severe colitis. Collectively, our results highlight IL-10 as a critical homeostatic macrophage-conditioning agent in the colon and define intestinal CX3CR1hi macrophages as a decisive factor that determines gut health or inflammation.

Data from four samples of commercially available PET geogrids (made either of yarns or bars), which were measured by BAM or other institute, are analyzed to discuss the procedure and problems of determining the chemical reduction factor RF CH associated with a certain service life. Estimates from Arrhenius extrapolation usually have very large statistical errors. The level of confidence must therefore be specified. A reliable estimate requires data from immersion tests below the glass transition temperature of PET. To extrapolate the time of reductions for each reduction factor at such low temperatures, one has to know the functional form of the mechanical degradation curve. It is shown how the degradation curve of the tensile strength may be obtained by determining the relation between increase in concentration of carboxyl end group (CEG) and decrease in tensile strength. Therefore, experimental studies to determine the chemical reduction factor should be accompanied by the measurements of the CEG concentration and the intrinsic viscosity. Furthermore, such measurements allow a non-ambiguous determination of the molecular mass. Hydrolytic molecular degradation will proceed continuously even at 20 °C with half-life of the inverse of the CEG concentration of 40–100 y. Nevertheless, small chemical reduction factors at a lifetime of 100 y are obtained with high level of confidence for materials with low initial CEG concentration and high molecular mass. This is shown by pooling data from samples with comparable CEG concentration, molecular mass and above all comparable intrinsic relation between increase in CEG concentration and decrease in strength. Therefore, the recommendation of ISO TR 20432, Table 2, for chemical reduction factors seems to be applicable to PET geogrids with index properties well below the one specified by the technical report. Whether these index properties are actually a sufficient condition to have small chemical reduction factors even at a very long service life is still an open question. The determination of chemical reduction factor should be based on aging experiments, at least for products with index properties close to the limiting values for the following reasons. (1) Even so standards are available, results of different laboratories on absolute values of CEG concentration and number averaged molecular mass differ to a certain extent. (2) Other factors, like crystallization, affect the mechanical degradation significantly. (3) There is no universally applicable form of the mechanical degradation curve.

Cytokines secreted at sites of inflammation impact the onset, progression, and resolution of inflammation. In this article, we investigated potential proresolving mechanisms of IFN-γ in models of inflammatory bowel disease. Guided by initial microarray analysis, in vitro studies revealed that IFN-γ selectively induced the expression of IL-10R1 on intestinal epithelia. Further analysis revealed that IL-10R1 was expressed predominantly on the apical membrane of polarized epithelial cells. Receptor activation functionally induced canonical IL-10 target gene expression in epithelia, concomitant with enhanced barrier restitution. Furthermore, knockdown of IL-10R1 in intestinal epithelial cells results in impaired barrier function in vitro. Colonic tissue isolated from murine colitis revealed that levels of IL-10R1 and suppressor of cytokine signaling 3 were increased in the epithelium and coincided with increased tissue IFN-γ and IL-10 cytokines. In parallel, studies showed that treatment of mice with rIFN-γ was sufficient to drive expression of IL-10R1 in the colonic epithelium. Studies of dextran sodium sulfate colitis in intestinal epithelial-specific IL-10R1–null mice revealed a remarkable increase in disease susceptibility associated with increased intestinal permeability. Together, these results provide novel insight into the crucial and underappreciated role of epithelial IL-10 signaling in the maintenance and restitution of epithelial barrier and of the temporal regulation of these pathways by IFN-γ.

Intact interleukin-10 receptor (IL-10R) signaling on effector and T regulatory (Treg) cells are each independently required to maintain immune tolerance. Here we show that IL-10 sensing by innate immune cells, independent of its effects on T cells, was critical for regulating mucosal homeostasis. Following wild-type (WT) CD4(+) T cell transfer, Rag2(-/-)Il10rb(-/-) mice developed severe colitis in association with profound defects in generation and function of Treg cells. Moreover, loss of IL-10R signaling impaired the generation and function of anti-inflammatory intestinal and bone-marrow-derived macrophages and their ability to secrete IL-10. Importantly, transfer of WT but not Il10rb(-/-) anti-inflammatory macrophages ameliorated colitis induction by WT CD4(+) T cells in Rag2(-/-)Il10rb(-/-) mice. Similar alterations in the generation and function of anti-inflammatory macrophages were observed in IL-10R-deficient patients with very early onset inflammatory bowel disease. Collectively, our studies define innate immune IL-10R signaling as a key factor regulating mucosal immune homeostasis in mice and humans.

This paper reports on classification methods applied and tested for land use classification in a semi-arid environment. Our study, conducted on two irrigated sites located in the Kairouan region, the largest irrigated region in Tunisia, compared Support Vector Machine (SVM) and Maximum Likelihood classification of SPOT-7 data. To produce a per-field classification a Mean-Shift Segmentation has been performed on the pansharpened SPOT-7 images. A field survey has been conducted. Accuracy assessment was done to evaluate the performance of the proposed using collect ground truth data on land use and extend of all the agricultural fields within the study areas obtained through filed survey.

Complete transection of the spinal cord leaves a gap of several mm which fills with fibrous scar tissue. Several approaches in rodent models have used tubes, foams, matrices or tissue implants to bridge this gap. Here, we describe a mechanical microconnector system (mMS) to re-adjust the retracted spinal cord stumps. The mMS is a multi-channel system of polymethylmethacrylate (PMMA), designed to fit into the spinal cord tissue gap after transection, with an outlet tubing system to apply negative pressure to the mMS thus sucking the spinal cord stumps into the honeycomb-structured holes. The stumps adhere to the microstructure of the mMS walls and remain in the mMS after removal of the vacuum. We show that the mMS preserves tissue integrity and allows axonal regrowth at 2, 5 and 19 weeks post lesion with no adverse tissue effects like in-bleeding or cyst formation. Preliminary assessment of locomotor function in the open field suggested beneficial effects of the mMS. Additional inner micro-channels enable local substance delivery into the lesion center via an attached osmotic minipump. We suggest that the mMS is a suitable device to adapt and stabilize the injured spinal cord after surgical resection of scar tissue (e.g., for chronic patients) or traumatic injuries with large tissue and bone damages.

The capacity of IL-10 and Tregs in the inflammatory tumor microenvironment to impair anticancer Th1 immunity makes them attractive targets for cancer immunotherapy. IL-10 and Tregs also suppress Th17 activity, which is associated with poor prognosis in several cancers. However, previous studies have overlooked their potential contribution to the regulation of pathogenic cancer-associated inflammation. In this study, we investigated the origin and function of IL-10–producing cells in the tumor microenvironment using transplantable tumor models in mice. The majority of tumor-associated IL-10 was produced by an activated Treg population. IL-10 production by Tregs was required to restrain Th17-type inflammation. Accumulation of activated IL-10+ Tregs in the tumor required type I IFN signaling but not inflammatory signaling pathways that depend on TLR adapter protein MyD88 or IL-12 family cytokines. IL-10 production limited Th17 cell numbers in both spleen and tumor. However, type I IFN was required to limit Th17 cells specifically in the tumor microenvironment, reflecting selective control of tumor-associated Tregs by type I IFN. Thus, the interplay of type I IFN, Tregs, and IL-10 is required to negatively regulate Th17 inflammation in the tumor microenvironment. Therapeutic interference of this network could therefore have the undesirable consequence of promoting Th17 inflammation and cancer growth.

IFN-γ produced by CD8+ cytotoxic T cells acts on neurons to induce Stat1-associated loss of dendrites and synapses in a mouse model of viral encephalitis., Neurons are postmitotic and thus irreplaceable cells of the central nervous system (CNS). Accordingly, CNS inflammation with resulting neuronal damage can have devastating consequences. We investigated molecular mediators and structural consequences of CD8+ T lymphocyte (CTL) attack on neurons in vivo. In a viral encephalitis model in mice, disease depended on CTL-derived interferon-γ (IFN-γ) and neuronal IFN-γ signaling. Downstream STAT1 phosphorylation and nuclear translocation in neurons were associated with dendrite and synapse loss (deafferentation). Analogous molecular and structural alterations were also found in human Rasmussen encephalitis, a CTL-mediated human autoimmune disorder of the CNS. Importantly, therapeutic intervention by IFN-γ blocking antibody prevented neuronal deafferentation and clinical disease without reducing CTL responses or CNS infiltration. These findings identify neuronal IFN-γ signaling as a novel target for neuroprotective interventions in CTL-mediated CNS disease.

Political thought grouped under the rubric ‘Christian Democracy’ is often considered as profoundly unoriginal and as the product of politicians and party activists (rather than political philosophers). This note puts forward the argument that there is an important—and in parts original—body of thought responding to the challenge of how to reconcile Christianity and modern democracy in nineteenth and twentieth century Europe. In rather schematic fashion it then traces three strategies for finding a place for Christianity—and Catholicism in particular—in the modern democratic order: the idea of creating or re-creating a Christian demos; the notion of constraining the demos through recognizably Christian institutions; and, lastly, Christian Democratic party politics. Apart from a research agenda, the article then suggests some lessons from this history, especially for thinking about the relationship between Islam and democracy.

Durch die hydrolytische Alterung andert sich die Zugfestigkeit eines Polyester-Bewehrungsgitters im Laufe der Zeit. Nach den Empfehlungen fur den Entwurf und die Berechnung von Erdkorpern mit Bewehrung aus Geokunststoffen (EBGEO) der DGGT wird dieser Effekt durch einen Abminderungsfaktor bei der Bemessung berucksichtigt. Es ist zwar im Prinzip festgelegt, wie man bei der Bestimmung eines solchen Faktors fur eine chemisch bedingte Materialveranderung vorgehen soll (ISO/TR 20432), es bleiben jedoch grose Freiheiten bei der Umsetzung. Die Fragen, die sich daraus bei Bewehrungsgittern aus Polyester ergeben, werden diskutiert. Es werden Bausteine eines einheitlichen Verfahrens vorgeschlagen, das sich nicht nur auf den Festigkeitsverlust, sondern auch auf die molekulare Veranderung konzentriert. Aging of PET geodrids Due to hydrolytic aging of the polyester material the tensile strength of PET-geogrids will change with time. According to the design recommendations (EBGEO) of the German Geotechnical Society DGGT this effect has to be taken into account by a factor of reduction. In principle the determination of the factor for chemical degradation is described in ISO/TR 20432. However, there is a considerable discretionary leeway in realizing the procedure for a special type of product. The questions, which occur from this for PET-geogrids, will be discussed in detail. Against this background building stones of a well-defined procedure are suggested, which considers not only mechanical degradation but also degradation in molecular weight.

IL-10, a cytokine with pleiotropic functions is produced by many different cells. Although IL-10 may be crucial for initiating protective Th2 responses to helminth infection, it may also function as a suppressive cytokine preventing immune pathology or even contributing to helminth-induced immune evasion. Here, we show that B cells and T cells produce IL-10 during murine Litomosoides sigmodontis infection. IL-10-deficient mice produced increased amounts of L. sigmodontis-specific IFN-γ and IL-13 suggesting a suppressive role for IL-10 in the initiation of the T-cell response to infection. Using cell type-specific IL-10-deficient mice, we dissected different functions of T-cell- and B-cell-derived IL-10. Litomosoides sigmodontis-specific IFN-γ, IL-5, and IL-13 production increased in the absence of T-cell-derived IL-10 at early and late time points of infection. In contrast, B-cell-specific IL-10 deficiency did not lead to significant changes in L. sigmodontis-specific cytokine production compared to WT mice. Our results suggest that the initiation of Ag-specific cellular responses during L. sigmodontis infection is suppressed by T-cell-derived IL-10 and not by B-cell-derived IL-10.

Recent illiberal turns in Hungary and Romania have prompted the question what, if anything, the EU could and should do to protect liberal democracy within Member States. The article discusses four principled concerns about democracy-saving EU interventions in Member States: that an institution which is itself largely undemocratic cannot credibly protect democracy; that there are in fact no common European standards which could be used to determine whether a Member State is departing from a shared European understanding of democracy; that interventions are per se illiberal; and, finally, that only small States will be subject to intervention, a form of EU hypocrisy which delegitimizes Brussels both in the States concerned and possibly across the EU as a whole. The article counters all these concerns and argues that the problem with intervention is not to be found at a theoretical level, but on a practical plane: as of now, the EU lacks a tool kit to intervene effectively in Member States; whatever it has recently used by way of sticks and carrots seems arbitrary or opportunistic. The article concludes by proposing a number of remedies for this situation.

Kunststoff-Dranelemente werden auch in Boschungen eingebaut. Da sie in der Regel aus mehreren Komponenten, namlich mindestens aus einem Drankern und einem Filtervliesstoff bestehen, hangt die Standsicherheit u. a. von der inneren Scherfestigkeit der Produkte ab. Diese kann entweder durch die reine Reibung der Komponenten untereinander oder durch die mechanische Festigkeit von Fugestellen zwischen den Komponenten bedingt sein, die schon bei der Produktion hergestellt werden. Im letzteren Fall ist nicht klar, wie Ergebnisse von Reibungsversuchen im Rahmenschergerat zu interpretieren sind. Vor diesem Hintergrund wird gezeigt, wie die Druck- und Scherkrafte, die ein Produkt langfristig aushalten kann, aus einem Reibungsversuch im Zusammenhang mit Kriechversuchen abgeleitet werden konnen. Dieses Vorgehen wird bei der Zulassung nach der Deponieverordnung fur den Einsatz in Deponieabdichtungen angewendet. On the internal shear strength of geocomposite drains. Geocomposite drains (GCD) are used on long and steep slopes. Since they are usually composed of different components, at least a drain core in connection with a nonwoven filter geotextile, the internal shear strength is of significant relevance for the slope stability. The internal shear strength may be due to pure friction forces between the different components or due to the mechanical strength of the bonding between the components achieved in a special production process. In the latter case the interpretation of the results of friction shear box tests is quite unclear. Against this background it is shown how the pressure and shear forces, which are acceptable for a product in the long run, may be derived from such a shear box test in combination with long-term creep tests. The procedure is used within the framework of the certification of the products for landfill cover systems according to the German landfill ordinance.

Mit Dichtungskontrollsystemen (DKS) werden Konvektionssperren in Oberflachenabdichtungssystemen von Deponien kontrolliert. Die Funktionsfahigkeit eines eingebauten DKS muss in jedem Projekt zuvor uberpruft werden. Diese projektspezifische Funktionsprufung des DKS selbst wird am Beispiel der Verwendung mit einer Kunststoffdichtungsbahn (KDB) diskutiert. Der grundsatzliche Aufbau, die zugrunde liegenden Messprinzipien und das Ziel der Prufung werden vorgestellt. Die Anforderungen an die nach der Deponieverordnung (DepV) zugelassenen Systeme hinsichtlich Betrieb, Leitungsfahigkeit und Konstruktion werden beschrieben. Dabei wird auf die Vorgaben der Richtlinie, die einer Zulassung zugrunde liegt, eingegangen. Das mogliche Vorgehen bei der projektspezifischen Kontrollprufung im Hinblick auf Aspekte wie Vorgehensweise, Zeitpunkt und Randbedingungen sowie ausere Einflussfaktoren werden diskutiert. Performance test of leak detection systems for tight barriers in landfill covers Leak detection systems (LDS) are used to control tight barriers in landfill cover systems. However, the efficiency of the installed LDS itself has to be verified in every landfill construction project. As an example the efficiency test for LDS used in connection with geomembranes is discussed in detail. The basic principles, the measuring techniques and objectives of the efficiency testing are described. The requirements for a certification of LDS under the terms of the new German landfill ordinance with regard to operation, capability and design are listed. The conditions necessary for a certification of LDS are introduced. Possible project related efficiency testing procedures with respect to the scope, time of convenience, general conditions as well as external influencing factors are discussed.

Rotation of the knee is a complex function with a considerable number of different active and passive structures involved. Specific injuries to one or more of the involved structures may cause rotatory laxity. These rotatory laxities can be classified with regard to the injured structures and the type of rotatory laxity.

Testing of the oxidative resistance of polyolefin based geosynthetics in autoclaves at high oxygen pressure has been suggested as an alternative method to conventional forced-air oven aging. The intention is to shorten considerably the testing time and to ensure that aging is performed under the condition of rate-controlled and not diffusion-limited oxidation. We compare data from high pressure autoclave tests (HPAT) with data from oven aging and water immersion tests at 80 °C. For this, the stabilization of the samples has to be taken into account. Polyolefin based geosynthetics are usually stabilized by two types of “packages” of antioxidants (AO), designated here as P1 and P2. P1 consists of phenols and phosphites, P2 of hindered amine stabilizers (HAS) in addition to a marginal stabilization P1 of the resin for the manufacturing process. Phenolic and phosphite AO are quickly consumed in the HPAT. Failure time is tremendously reduced compared to forced-air oven aging or water immersion. The results are discussed within the framework of a basic autoxidation scheme (Wise et al., 1997). The reduction is much greater than expected from theoretical considerations. Therefore, a direct and degrading reaction of oxygen with the AO has to be assumed. In case of HAS, the time dependence of the degradation of tensile properties in the HPAT is significantly different from the dependence observed in conventional forced-air oven aging and their effectiveness is likewise strongly reduced. A conclusive interpretation of HPAT results needs a better understanding of what happens to the AO at high oxygen pressure.

Asymptomatic thyroid nodules are very common and detected with increasing frequency by radiological investigations of the neck as so-called “incidentalomas”. If a thyroid nodule is found, the question arises how to proceed with this case. The goal is to recognize the very rare malignant nodules and to perform an adequate therapy. Every work-up of a thyroid nodule includes functional evaluation by determination of thyroid stimulating hormone (TSH). Is the level of the hormone suppressed, a scintigraphy is indicated to rule out a hot thyroid nodule implying a benign finding. Ultrasound is the imaging of choice for the thyroid gland and provides information with respect to size, number and configuration of the nodes. Depending on sonographic evaluation and other possible risk factors, a fine-needle aspiration biopsy of the node is performed. Based on the cytologic findings further therapeutic procedures are determined.

Defects of the intracellular enzyme 3′ repair exonuclease 1 (Trex1) cause the rare autoimmune condition Aicardi–Goutières syndrome and are associated with systemic lupus erythematosus. Trex1−/− mice develop type I IFN–driven autoimmunity, resulting from activation of the cytoplasmic DNA sensor cyclic GMP–AMP synthase by a nucleic acid substrate of Trex1 that remains unknown. To identify cell types responsible for initiation of autoimmunity, we generated conditional Trex1 knockout mice. Loss of Trex1 in dendritic cells was sufficient to cause IFN release and autoimmunity, whereas Trex1-deficient keratinocytes and microglia produced IFN but did not induce inflammation. In contrast, B cells, cardiomyocytes, neurons, and astrocytes did not show any detectable response to the inactivation of Trex1. Thus, individual cell types differentially respond to the loss of Trex1, and Trex1 expression in dendritic cells is essential to prevent breakdown of self-tolerance ensuing from aberrant detection of endogenous DNA.

After a spinal cord injury (SCI) a scar forms in the lesion core which hinders axonal regeneration. Bridging the site of injury after an insult to the spinal cord, tumor resections, or tissue defects resulting from traumatic accidents can aid in facilitating general tissue repair as well as regenerative growth of nerve fibers into and beyond the affected area. Two experimental treatment strategies are presented: (1) implantation of a novel microconnector device into an acutely and completely transected thoracic rat spinal cord to readapt severed spinal cord tissue stumps, and (2) polyethylene glycol filling of the SCI site in chronically lesioned rats after scar resection. The chronic spinal cord lesion in this model is a complete spinal cord transection which was inflicted 5 weeks before treatment. Both methods have recently achieved very promising outcomes and promoted axonal regrowth, beneficial cellular invasion and functional improvements in rodent models of spinal cord injury. The mechanical microconnector system (mMS) is a multi-channel system composed of polymethylmethacrylate (PMMA) with an outlet tubing system to apply negative pressure to the mMS lumen thus pulling the spinal cord stumps into the honeycomb-structured holes. After its implantation into the 1 mm tissue gap the tissue is sucked into the device. Furthermore, the inner walls of the mMS are microstructured for better tissue adhesion. In the case of the chronic spinal cord injury approach, spinal cord tissue - including the scar-filled lesion area - is resected over an area of 4 mm in length. After the microsurgical scar resection the resulting cavity is filled with polyethylene glycol (PEG 600) which was found to provide an excellent substratum for cellular invasion, revascularization, axonal regeneration and even compact remyelination in vivo.

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and, in most cases, is of pro- or pre-B cell origin (B-ALL). The receptor tyrosine kinase KIT is expressed by hematopoietic stem and precursor cells. Gain-of-function mutations of KIT cause systemic mastocytosis, which is characterized by abnormal accumulations of mast cells. We previously reported a mouse model of mastocytosis based on conditional expression of a constitutively active Kit protein. Half of these animals developed leukemic disease of B-lineage origin. Herein, we report that this condition bears striking similarities to human B-ALL. The immuno-phenotype of the leukemic cells was compatible with a pro-B-cell origin, as was the finding of immunoglobulin heavy-chain gene rearrangements in all cases, whereas light-chain loci were mostly not rearranged. Leukemogenesis was independent of pre-B-cell receptor expression. Primary leukemic cells and permanent cell lines derived from these were serially transplantable and rapidly killed the recipients. In a few animals, the leukemia was of T-cell origin with abnormal CD4/8 double-positive T-cell precursors dominating in the circulation. In summary, we report a novel ALL mouse model that may prove useful for in vivo drug testing and identification of novel oncogenic mutations and principles.