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The human Interleukin-1 receptor-associated protein kinase IRAK-1 is a highly specific signaling molecule activated by the Toll/IL-1 receptor family. It is a multidomain protein consisting of an N-terminal death domain, a regulatory ProST (proline-, serine-, threonine-rich) region, a conventional serine/threonine protein kinase domain and a large C-terminal rest. IRAK-1 mediates between the active receptor complex and downstream signaling events such as activation of NFκB. This adapter function is guaranteed by protein interactions of the N-terminal death domain to MyD88 and of the C-terminus to TRAF6. The signaling function of IRAK-1 is independent of its enzymatic activity. The kinase domain and the ProST region serve as a self-activating kinetic switch module in IRAK-1. Two different phosphorylation events take place in a sequential fashion in IRAK-1. The first is an autophosphorylation of the kinase domain resulting in full enzymatic activity. This is followed by multiple phosphorylations in the ProST region. The introduction of negative charges adjacent to the death domain has two consequences: First hyperphosphorylated IRAK-1 dissociates from the upstream adapter MyD88 and thus leaves the active receptor complex allowing optimal interaction with the downstream adapter TRAF6. Second, hyperphosphorylated IRAK-1 is targeted to the proteasome where it is proteolytically degraded and thus removed out of the signaling chain. This self-limitation guarantees a transient IL-1 signal. This regulatory function is completely dispensable for IRAK-1's adapter function as a signaling molecule. In summary, IRAK-1 is a highly-sophisticated adapter molecule in the signaling pathway of the Toll/IL-1 receptor family which regulates its own availability as a signaling component by autophosphorylation and autoinduced proteolytical degradation (summarized in Fig. 1).

Two forms of soluble human type II interleukin (IL)-1 receptor (shIL-1RII) were generated, one consisting of the complete extracellular three immunoglobulin (Ig)-like domains and one containing only the first two N-terminal Ig-like domains. Both forms bound IL-1beta with a dissociation constant (K(d)) of 200 pM and neutralized IL-1beta in a bioassay. They did not bind or neutralize IL-1alpha. This demonstrates that the two Ig-like domains of shIL-1RII are sufficient to bind IL-1beta with an affinity comparable to full length shIL-1RII. This suggests that this short form of shIL-1RII contributes to the anti-inflammatory effect of soluble IL-1 receptors in vivo.

Isolated hyperthermic perfusion of the liver was performed for 45 min in 27 pigs via hepatic artery and portal vein at mean inflow temperatures between 40.7 and 41.2 degrees C. In two study groups B and C (n = 9 pigs each) 50 microg recombinant human tumor necrosis factor-alpha (rhTNFalpha) per kg body weight were added to the perfusate, whereas in a control group A liver perfusion was done without rhTNFalpha. Before reperfusion the livers were washed out with Ringer's solution in all groups followed by a protein solution in group C. At 30 and 60 min after reperfusion the maximum systemic rhTNFalpha concentrations were significantly higher in group B with 68 and 61 ng/ml compared to 14.5 and 14.9 ng/ml in group C (p0. 05). Mean systemic porcine TNFalpha concentration was significantly higher in group B (217 pg/ml) compared to group C (50 pg/ml) 30 min after reperfusion (p = 0.012). Survival was 7/9 in group A and C and only 2/9 in group B with 6/7 pigs dying due to severe cardiopulmonary failure within 12 h after operation. In surviving pigs of group A and C only mild and transient hepatotoxicity was registered. The presented study underlines the feasibility of high dose rhTNFalpha application in an isolated hyperthermic liver perfusion system. Washout of the liver with a protein solution before reperfusion reduces systemic TNFalpha levels as well as associated lethal cardiocirculatory and hepatotoxic side effects.

Interleukin-1 (IL-1) stimulates the association of the IL-1 receptor-associated protein kinase (IRAK) with the heterodimer of IL-1RI and IL-1RAcP via the adapter protein MyD88. In the receptor complex IRAK becomes heavily phosphorylated and concomitantly activated. Here we show that overexpression of a kinase-inactive mutant of IRAK (K239S) inhibits neither IL-1-stimulated activation of the transcription factor NF-κB, nor that of the c-Jun N-terminal kinase nor IL-2 production in murine EL-4 cells, but enhances these effects in a manner comparable to wild type IRAK. This strongly suggests that the intrinsic kinase activity is not required for downstream signaling via IRAK.

Intelligent antennas offer the possibility of greatly increasing the capacity of cellular mobile radio systems. We give a comprehensive overview of the literature concerning model scenarios for applications of direction-selective intelligent antennas. Measurement campaigns and simplified models are described that have been derived from these measurements or from physical considerations. Furthermore, directional fading simulators are reviewed which are essential for testing of smart antenna systems.

We report on vertical-cavity surface-emitting lasers (VCSELs) and laser arrays providing high output powers in the 980-nm wavelength regime. Extensive investigations on size scaling behavior of single top- and bottom-emitting devices concerning fundamental electrooptical and thermal properties show limits of attainable output characteristics. Maximum experimentally achieved continuous-wave (CW) optical output powers at room temperature are 180 and 350 mW for top- and bottom-emitting VCSELs, respectively. Detailed analysis on the thermal interaction between closely spaced elements have been carried out to describe the thermally induced power limitations of two-dimensional arrays. Fabricated heat sunk bottom-emitting arrays of 23 elements and 40-/spl mu/m aperture size of individual elements show output powers of 0.56 W CW at room temperature and 0.8 W actively cooled, resulting in 0.33 kW/cm/sup 2/ and 0.47 kW/cm/sup 2/ maximum spatially averaged optical power density, respectively.

The association and activation of the IL-1 receptor-associated protein kinase (IRAK) to the IL-1 receptor complex is one of the earliest events detectable in IL-1 signal transduction. We generated permanent clones of the murine T cell line EL4 6.1 overexpressing human (h)IRAK to evaluate the role of this kinase in IL-1 signaling. Overexpression of hIRAK enhanced IL-1-stimulated activation of the transcription factor NFkappaB, whereas a truncated form (N-IRAK) specifically inhibited IL-1-dependent NFkappaB activity. In clones stably overexpressing hIRAK a weak constitutive activation of NFkappaB correlated with a low basal IL-2 production which was enhanced in an IL-1-dependent manner. Compared to the parental cell line the dose-response curve of IL-1-induced IL-2 production was shifted in both potency and efficacy. These results demonstrate that IRAK directly triggers NFkappaB-mediated gene expression in EL4 cells. Qualitatively different effects were observed for the IL-1-induced activation of stress-activated protein (SAP) kinases: permanent overexpression of IRAK did not affect the dose dependence but prolonged the kinetics of IL-1-induced activation of SAP kinases, suggesting that this signaling branch may be regulated by distinct mechanisms.

In der vorliegenden Arbeit wird die Entwicklung der Mikrostruktur, gekennzeichnet durch die Merkmale Versetzungsdichte, Partikelvolumenanteil und -abstand bei Hochtemperaturkriechbeanspruchung, der Eisenbasislegierung Incoloy Alloy 800HT (X10 NiCrAlTi 32 20 HT) untersucht. Zur Beschreibung der Evolution der Mikrostruktur in Abhangigkeit von Temperatur und Kriechverformung werden isotherme Warmebehandlungen und Kriechexperimente bei 800° / 800° und 70MPa sowie 900° / 900° und 45MPa durchgefuhrt. Die Untersuchung der sich durch die Beanspruchungen einstellenden Gefugeanderugen erfolgt mit Methoden der Elektronenmikroskopie, vornehmlich im Transmissionselektronenmikroskop. Eine detaillierte Auswertung der sich ergebenden Versetzungsdichten und Grosen der ausgeschiedenen Karbide wird mit den Zeitstandkenngrosen in Beziehung gesetzt, analysiert und diskutiert. Evolution of the Microstructure in Alloy 800HT under High Temperature Creep Load In the present work the microstructural evolution under isothermal and high temperature creep conditions is studied for the iron-base-alloy Incoloy Alloy 800HT (X10 NiCrAlTi 32 20 HT) at temperatures of 800° and 900° and stresses of 70 MPa and 45 MPa resp. To describe the microstructure changes under creep stress loading and constant test temperature the dislocation density, particle size and mean planer interparticle spacing where investigated using transmission electron microscopy. The results of the dislocation density and particle morphology measurements are compared and discussed in the context of creep deformation, heat treatment conditions and creep behaviour.

Interleukin-1 (IL-1) is a central mediator of the immune system involved in acute and chronic inflammatory responses. Although the sequences of two types of IL-1 receptors are known, the exact molecular events resulting in signal transduction and coupling to downstream signaling elements remain unclear. The recently cloned IL-1 receptor accessory protein (IL-1RAcP) has been suggested as a co-receptor molecule for IL-1RI, supported by the observation that its expression correlates to IL-1 responsiveness. We transfected the EL-4 subline D6/76 with IL-1RAcP cDNA. This cell line is an IL-1 non-responder expressing IL-1RI but lacking constitutive IL-1RAcP expression. The expression of IL-1RAcP in EL-4 D6/76 was sufficient to restore IL-1-induced activation of interleukin-1 receptor-associated kinase and of stress-activated protein kinases, translocation of the transcription factors NFkappaB and IL-1 NF to the nucleus, and induction of IL-2 mRNA synthesis. These results proved that IL-1RAcP is an indispensible molecule in the IL-1 receptor signal transduction complex, necessary to link events on the plasma membrane level to downstream signaling pathways, allowing IL-1-dependent activation of transcription factors and gene expression.

Background/Objective: The objective was to establish the characteristics of antenatal attendees in Faith Medical Centre, a private health facility in Benin City who have asymptomatic bacteriuria (ASB) as well as to determine the relationship between ASB and socioeconomic status. Methods: It was a descriptive, cross-sectional study involving 240 pregnant women who presented in the course of antenatal care from January to April 2009. With the aid of a questionnaire patients who were recruited for the study had their socio-demographic data and relevant gynecological and drug history recorded. A physical examination was done to document temperature, height, weight and symphysiofundal height. A clean-catch midstream urine sample was collected for microscopy and culture. White blood cell count of≥5/hpf and/or bacteria count of≥1/hpf of urine was considered significant for urine microscopy and a single colony count of ≥105/ml from two consecutive urine samples was considered significant for urine culture. Results: The prevalence of ASB was 13.8% by urine culture and 43.8% by urine microscopy among antenatal attendees in Faith Medical Centre, Benin City. There was no relationship between ASB and socio-economic factor (P value=0.1267). There was also no significant specific trend between ASB and age (P value=0.0578). Using urine culture as gold standard, the sensitivity of urine microscopy was 90.9%, the specificity was 49.3%, the positive predictive value was 22.2% and the negative predictive value was 97.1%. Conclusion: ASB in pregnancy is common in Faith Mediplex and has no statistically significant relationship with socioeconomic status. The current practice of diagnosing and treating ASB based on urine microscopy needs to be reviewed since the specificity of urine microscopy is very low. Also the practice of screening pregnant women only at the time of booking can lead to under-diagnosis of ASB. This is so because most women who develop this condition later in the course of antenatal care will be missed.

Background Coeliac disease is an autoimmune disorder that is considered to affect approximately one in 100 people. In the UK, gluten-free (GF) foods can be prescribed by general practitioners (GPs) to treat this condition and there are national guidelines on the quantities of GF food an individual should receive on prescription. Information on actual prescribing behaviour by GPs, and how this compares with guideline recommendations, is scarce. The present study aimed to describe GPs prescribing practice of GF foods, within one locality in the UK, comparing this with national guidelines. Methods A retrospective evaluation of GP electronic medical records for all patients with a gluten-sensitive enteropathy diagnosis and/or those prescribed GF food between April 2010 and March 2011 was carried out in 16 GP practices in the west of Scotland, serving a total of 85 667 patients. Results Of 175 (0.18% of the total practice population) patients, 152 were identified with coeliac disease, eight with dermatitis herpetiformis and six with both conditions. A further nine patients received GF foods on prescriptions with no recorded diagnosis. There was a positive association between adherence to the prescribing guidelines and female sex (P

We have analyzed the induction of the receptor for the anaphylatoxic peptide C3a (C3aR) by the immunomodulator IFN-gamma, the phorbol ester PMA, and dibutyryl cAMP (Bt2cAMP) in comparison with the C5a receptor (C5aR, CD88). For U937 cells, IFN-gamma and Bt2cAMP up-regulated the C3aR to the same extent, whereas Bt2cAMP was 20-fold more effective in C5aR induction. PMA increased the expression of the C5aR, and acted synergistically with IFN-gamma. In contrast, PMA did not increase specific 125I-hC3a binding, and actually antagonized C3aR induction by IFN-gamma. Two related human cell lines of the myeloblastic/monocytic lineage, HL-60 and Mono Mac 6, showed inducibility of the C3aR similar to U937 cells. The two receptors showed subtle differences in signal transduction. Despite comparable numbers of both receptors, IFN-gamma potentiated activation of the C5aR but not the C3aR, as measured by an increase in free cytosolic Ca2+ upon ligand activation. Interestingly, Bt2cAMP-treatment led to a functional response to C3a in U937 cells. Such differences in receptor regulation and signaling might underlie the partly differing physiologic effects of C3a and C5a on, for example, chemotaxis, induction of oxidative burst, or immunoregulatory functions.

Normally, the alloy NiMo28 is used in the solution annealed and quenched condition in which it has a face centred cubic matrix structure. The matrix of the material is supersaturated with molybdenum and, at temperatures above 800 °C, has a tendency to form intermetallic precipitates such as the Ni4Mo-ordered phase leading to the embrittlement of the NiMo28 alloy during hot working. For this reason, the aim of these investigations was to optimise the alloy by reducing its tendency to embrittle. The TEM-analyses carried out served to investigate the precipitation of the material as a function of its iron content after ageing at 700 °C. The change in hardness and in the lattice constants of the NiMo28-specimens with iron content were also determined.

Correctly identifying associations of genes with diseases has long been a goal in biology. With the emergence of large-scale gene-phenotype association datasets in biology, we can leverage statistical and machine learning methods to help us achieve this goal. In this paper, we present two methods for predicting gene-disease associations based on functional gene associations and gene-phenotype associations in model organisms. The first method, the Katz measure, is motivated from its success in social network link prediction, and is very closely related to some of the recent methods proposed for gene-disease association inference. The second method, called Catapult (Combining dATa Across species using Positive-Unlabeled Learning Techniques), is a supervised machine learning method that uses a biased support vector machine where the features are derived from walks in a heterogeneous gene-trait network. We study the performance of the proposed methods and related state-of-the-art methods using two different evaluation strategies, on two distinct data sets, namely OMIM phenotypes and drug-target interactions. Finally, by measuring the performance of the methods using two different evaluation strategies, we show that even though both methods perform very well, the Katz measure is better at identifying associations between traits and poorly studied genes, whereas Catapult is better suited to correctly identifying gene-trait associations overall. The authors want to thank Jon Laurent and Kris McGary for some of the data used, and Li and Patra for making their code available. Most of Ambuj Tewari's contribution to this work happened while he was a postdoctoral fellow at the University of Texas at Austin.

The mouse CD5 positive pre-B cell line SPGM-1 can be induced to switch its lineage commitment towards macrophage differentiation by treatment with a combination of phorbol ester and a calcium ionophore. When cultured with these reagents the pre-B cells ceased to proliferate and rapidly became adherent to plastic surfaces. This morphological change was accompanied by the loss of pre-B cell-specific surface markers, such as PB76 and most prominently the mu heavy chain of the immunoglobulin receptor complex. In addition, the mRNA of the surrogate light chain lambda 5 disappeared while the induction of lysozyme mRNA could be detected. Differentiated SPGM-1 cells phagocytosed latex beads and showed nonspecific esterase activity. The high efficiency and speed of differentiation in this cellular system makes SPGM-1 a highly suitable model for studying the phenomenon of lineage switching during hemopoesis.

On human mature monocytes the immunomodulator IFN-gamma has been shown to down-regulate the receptor for the anaphylatoxic peptide C5a (CD88, C5aR). In this study, we show that in immature myelo-/monoblastic U937, HL60, and MonoMac6 cells, IFN-gamma induces C5aR-ligand binding activity. In U937 cells, this induction cannot be blocked by the protein kinase C inhibitor staurosporine. An increase in free cytosolic Ca2+ upon ligand binding indicates functional coupling of this receptor in U937 and HL-60 cells. G-Proteins involved in this C5a responsiveness after IFN-gamma induction are completely pertussis toxin sensitive. Our data suggest that an additional pertussis toxin-resistant pathway exists in U937 cells after induction by dibutyryl cAMP. However, this is not due to changes in the mRNA level of the pertussis toxin-insensitive G-protein subunit G alpha 16. Induction by dibutyryl cAMP, but not that by IFN-gamma, resulted in C5a-dependent release of N-acetyl-beta-D-glucosaminidase, further highlighting functional differences in the effects of the inducers. Our data show an IFN-gamma-dependent increase in C5aR expression and suggest a maturation-related change in signaling of the C5aR, presumably at the level of receptor coupling.

There are still some ambiguities on the surface-enhanced Raman scattering (SERS) of Al surfaces. In this work, some experimental results for normal Raman scattering and resonance Raman scattering from p -nitrobenzoic acid (PNBA), Rhodamine 6G and dye 1555 adsorbed on substrates of metal Al and aluminum oxide are reported. We used the techniques of dipping, immersing and spinning to deposit molecules on substrates which were produced by lithography or mechanical polishing. All the results show that there is no enhancement for the molecules on these surfaces. The observed Raman bands from PNBA adsorbed on a substrate of lithographically produced Al were from bulk molecules of PNBA. The results are well explained by the antenna resonator model of SERS.

Any system to compensate countries for reduced emissions from deforestation and forest degradation (REDD+) requires a historical reference level against which future performance can be measured. Here we examine the possibilities Sri Lanka, a small forest country with limited data on forest carbon stocks, has to get ready for REDD+. We construct a historical reference level using available forest inventory data combined with updated 2008 and 2009 in situ carbon density data for Sri Lankan forests. Furthermore, we use a combination of qualitative and quantitative data to attribute the clearing of Sri Lankan forests in the latest years for which national forest inventory data are available, 1992-1996, to various proximate drivers and to estimate the opportunity cost of forest conservation. We estimate that baseline deforestation emissions in Sri Lanka amounted to 17 MtCO(2) yr(-1) in the 1992-1996 period, but conclude that it is challenging for Sri Lanka to produce a robust and accurate reference level due to the lack of nationally based inventories. We find that the majority of forest clearing (87%) is due to small-scale, rainfed farming, with the two other major drivers being rice and tea cultivation. Further, Sri Lankan revenues from REDD+ participation could be substantial, but they are sensitive to REDD+ policy transaction cost, highly uncertain timber revenues, and particularly the carbon price paid for emission reductions. The latter needs to be higher than $5-10/tCO(2) if there are to be substantial incentives for Sri Lanka to participate in REDD+. There is, however, a large gap in the knowledge of deforestation drivers that needs to be filled if Sri Lanka is to formulate an effective policy response to forest degradation in REDD+. For successful REDD+ implementation in Sri Lanka to happen, technological assistance, readiness assistance, and continued political momentum are crucial. Funding Agencies|Swedish Energy Agency||Swedish International Development and Cooperation Agency||Goteborg Energi

The presence of sugar receptors on human myeloid leukemia cells was comparatively assessed by a highly sensitive binding assay, employing a panel of 14 types of neoglycoenzymes (chemically glycosylated Escherichia coli beta-galactosidase). The selected carbohydrate ligands mainly encompass common components of natural glycoconjugates as mono- or disaccharides. The monocytoid cells of the THP-1 line, the very young myeloblasts and the myeloblasts of the lines KG-1a and KG-1, the promyelocytes of the HL-60 line, and the early myeloblasts/erythroblasts of the K-562 line displayed a nonuniform pattern of specific binding with quantitative differences at a fixed, nonsaturating concentration of the probes. Scatchard analysis in four cases corroborated the indication of cell-type-related differences between the various cell lines. To test whether the detectable cellular sugar-binding sites can mediate adhesion to glycoligands, a rather simple model matrix of nitrocellulose-immobilized neoglycoproteins was first used. In comparison to the carbohydrate-free carrier protein significant cell adhesion was observed primarily with neoglycoproteins that exposed galactose, N-acetylgalactosamine, N-acetylglucosamine, mannose, and fucose moieties among the 11 tested types of carbohydrate residue. Subsequently, human bone marrow stromal cell layers were tested as a model matrix with increased levels of physiological relevance and complexity. Mixtures of carbohydrate and neoglycoprotein were employed as inhibitors of an interaction via lectins between the stromal and the tumor cells. The carbohydrate-dependent alterations of this parameter revealed cell-type-associated properties. Tumor cell binding was significantly decreased for not more than two lines with the effective sugars, namely N-acetylgalactosamine, mannose, fucose, and sialic acid.

Despite the recent popularity of conditional cash transfers (CCT) and payments for environmental services (PES) programs, what determines their success is not well understood. We developed a conceptual framework to give insight into some of the main determinants of CCT and PES program efficiency that hope to increase investments in human and environmental capital. We used a simple agent-based model and validated the results with empirical data from existing programs. We show that 1) the share of participants who meet the program’s conditions at baseline is a powerful predictor of program efficiency, (2) and selection bias erodes program efficiency to a large extent. (Selection bias stems from agents who already meet program criteria and who self-select into programs at higher rates than those who do not meet the conditions.) Based on these results, we discuss possibilities for improving efficiency—mainly by targeting applicants or increasing payments—and criteria for evaluating and choosing CCT, PES, or other policy instruments.

New German legislative ordinances prescribe hygiene control in nursing homes and homes for the aged, e. g. the Law for Protection against Infectious Diseases and in North-Rhine Westphalia the Public Health Law. However, there are as yet no clearly defined standards of hygiene because the special features of nursing homes must be considered when applying the "Guidelines for Hospital Hygiene and Prevention of Infections" issued by the Robert Koch Institute. Hence, specific recommendations are given for hygiene of the hands, disinfection, hygienic treatment care, protective and professional clothing, washing of textiles, central kitchen, disposal of waste, house cleaning and handling of drugs and medicines.

Die Immunpharmakologie hat sich zu einer Leitwissenschaft für innovative Arzneimittel entwickelt. Das Buch stellt das Grenzgebiet zwischen Immunologie und Pharmakologie umfassend dar. Aus dem Inhalt: - Eine kurze Einführung in das Immunsystem - Die therapeutische Nutzung des Immunsystems - Impfung, Immunstimulanzien, Antikörper, Zytokine und Immunzellen - Wiederherstellung eines gestörten Immunsystems - Primäre Immunschwächeerkrankungen, AIDS und Tumorimmunologie - Pharmakologische Immunsuppression – Entzündung, Autoimmunerkrankungen, Allergie und Transplantation Bevor Arzneistoffe, Krankheiten und Therapie beschrieben werden, führt jedes Kapitel zunächst in das Thema ein. Daher sind keine speziellen Kenntnisse vorausgesetzt. Das Buch richtet sich an Studierende höherer Semester in Medizin, Pharmazie und Biologie, sowie an Ärzte und Apotheker.

IL-1alpha, like IL-1beta, possesses multiple inflammatory and immune properties. However, unlike IL-1beta, the cytokine is present intracellularly in healthy tissues and is not actively secreted. Rather, IL-1alpha translocates to the nucleus and participates in transcription. Here we show that intracellular IL-1alpha is a chromatin-associated cytokine and highly dynamic in the nucleus of living cells. During apoptosis, IL-1alpha concentrates in dense nuclear foci, which markedly reduces its mobile nature. In apoptotic cells, IL-1alpha is retained within the chromatin fraction and is not released along with the cytoplasmic contents. To simulate the in vivo inflammatory response to cells undergoing different mechanisms of death, lysates of cells were embedded in Matrigel plugs and implanted into mice. Lysates from cells undergoing necrosis recruited cells of the myeloid lineage into the Matrigel, whereas lysates of necrotic cells lacking IL-1alpha failed to recruit an infiltrate. In contrast, lysates of cells undergoing apoptotic death were inactive. Cells infiltrating the Matrigel were due to low concentrations (20-50 pg) of the IL-1alpha precursor containing the receptor interacting C-terminal, whereas the N-terminal propiece containing the nuclear localization site failed to do so. When normal keratinocytes were subjected to hypoxia, the constitutive IL-1alpha precursor was released into the supernatant. Thus, after an ischemic event, the IL-1alpha precursor is released by hypoxic cells and incites an inflammatory response by recruiting myeloid cells into the area. Tissues surrounding the necrotic site also sustain damage from the myeloid cells. Nuclear trafficking and differential release during necrosis vs. apoptosis demonstrate that inflammation by IL-1alpha is tightly controlled.

Climate policy will create both disincentives and incentives for tropical deforestation. Disincentives if the carbon emissions from forest clearing are priced, as is currently being discussed within the United Nations Framework Convention on Climate Change (UNFCCC); incentives as a price on carbon will increase the demand for carbon-neutral energy sources, including bioenergy, making deforestation for biomass cultivation increasingly profitable. The question is whether the increased cost for forest clearing, through the price on carbon emissions, will be enough to counter-balance the increased profitability of deforestation through the escalating value of agricultural land. In an attempt to answer this question we analyze the profitability of tropical deforestation and subsequent bioenergy production, taking oil palm plantations as an illustrative example. We estimate that deforesting for palm oil bioenergy production is likely to remain highly profitable, even in the face of a price on the carbon emissions from forest clearing. Current efforts to include carbon emissions from tropical deforestation in a future international climate regime, while a step in the right direction, may therefore not suffice as protection for the world’s tropical forests. Additional, and stronger, protection measures for the world’s tropical forests will still be needed.

Das Buch gibt eine knappe Einführung in die Grundlagen der Immunologie. Die zellulären Träger der Immunreaktionen werden beschrieben und darauf aufbauend die zentralen Abwehr-Mechanismen am Beispiel der Infektabwehr. Dabei wird deutlich, dass das Immunsystem an wichtigen biologischen Vorgängen wie Schwangerschaft und Tumor-abwehr beteiligt ist. Die Kenntnis dieser biologischen Prozesse ist auch die Grundlage, um viele Krankheiten zu verstehen.

Ligand binding in the TLR/IL-1R family results in the transient formation of an intracellular signaling complex, which contains, amongst others, the serine/threonine-specific kinase IL-1R-associated kinase 1 (IRAK-1). Concomitantly, the kinase function of IRAK-1 becomes activated, resulting in massive autophosphorylation and finally in the dissociation of the initially constituted signaling complex. The death domain (DD) of IRAK-1 mediates the interaction with other molecules of the signaling complex, e.g., the adaptor MyD88, the silencer Tollip, and the activator kinase IRAK-4. The conserved threonine at position 66 (T66), located within the DD, is a putative autophosphorylation target site. Here, we provide evidence that T66 critically impacts the secondary structure of the IRAK-1 DD. Thereby, it ensures the transient manner of interactions between IRAK-1 and the other signaling molecules. This essential role, however, is not regulated by phosphorylation of T66 itself.

Lack of the IL-1 receptor accessory protein (IL-1RAcP) abrogates responses to IL-33 and IL-1 in the mouse thymoma clone EL-4 D6/76 cells. Reconstitution with full-length IL-1RAcP is sufficient to restore responsiveness to IL-33 and IL-1. IL-33 activates IL-1 receptor-associated kinase-1, cJun-N-terminal kinase, and the NF-κB pathway in an IL-1RAcP-dependent manner and results in IL-2 release. IL-33 is able to induce the release of proinflammatory cytokines in bone marrow-derived (BMD) mast cells, indicating that IL-33 may have a proinflammatory potential like its relatives IL-1 and IL-18, in addition to its Th2-skewing properties in the adaptive response described previously. Blocking of murine IL-1RAcP with the neutralizing antibody 4C5 inhibits response of mouse thymoma cells and BMD mast cells to IL-33. The interaction of either membrane-bound or soluble forms of IL-1RAcP and IL-33Rα-chain depends on the presence of IL-33, as demonstrated by coimmunoprecipitation assays. These data demonstrate that IL-1RAcP is indispensable for IL-33 signaling. Furthermore, they suggest that IL-1RAcP is used by more than one α-chain of the IL-1 receptor family and thus may resemble a common β-chain of that family.

The Stern Review has had a major influence on the policy discussion on climate change. One reason is that the report has raised the estimated cost of unmitigated climate damages by an order of magnitude compared to most earlier estimates, leading to a call for strong and urgent action on climate change. Not surprisingly, severe criticism has been levied against the report by authors who think that these results hinge mainly on the use of a discount rate that is too low. Here we discuss the Ramsey rule for the discount rates and its implications for the economics of climate change. While we find no strong objections to the discounting assumptions adopted in the Stern Review, our main point is that the conclusions reached in the review can be justified on other grounds than by using a low discount rate. We argue that nonmarket damages from climate change are probably underestimated and that future scarcities that will be induced by the changing composition of the economy and climate change should lead to rising relative prices for certain goods and services, raising the estimated damage of climate change and counteracting the effect of discounting. We build our analysis on earlier research (Hoel and Sterner 2007) that has shown that the Ramsey discounting formula is somewhat modified in a two-sector economy with differential growth rates. Most importantly, such a model is characterized by changing relative prices, something that has major implications for a correct valuation of future climate damages. We introduce these results into a slightly modified version of the DICE model (Nordhaus 1994) and find that taking relative prices into account can have as large an effect on economically warranted abatement levels as can a low discount rate.

Myocardial transplantation of myocytes and bone marrow derived cells is currently under clinical evaluation as an alternative therapy of heart failure. One of the main problems of all clinical studies performed so far is the inability to track the fate of the transplanted cells. The aim of our study was the development of a potentially clinically applicable approach, which allows for detection of the transplanted cells without need for collection of tissue samples. Fetal canine cardiomyocytes were labelled with the non-toxic fluorescent membrane dye Vybrant CM-DiI and delivered into the free wall of the left ventricle of adult mongrel dogs. For subsequent tracking of the cellular graft, the dogs underwent a second operation in which an intra-vital microscope was mounted above the exposed heart within the thorax. A special computer software eliminated artefacts caused by myocardial contraction. Two months after transplantation, the fluorescent graft was macroscopically visible by intra-vital microscopy using a 10x magnification. Histological studies served as microscopic control and confirmed the existence of DiI-labelled cells at the site of injection. Connexin 43 immunoreactivity was visible at junctional complexes between donor and recipient cells, suggesting morphologic and functional coupling as a result of gap junction formation. Our results demonstrate that in vivo detection of transplanted cells in the heart is feasible. Further technical adjustments should allow for thoracoscopic/endoscopic application of this method, making it appropriate for use in other organs and in clinical studies.

Purpose of Study: This phase I study assessed tolerability and local effect of a liposome dispersion with povidone-iodine (polyvinylpyrrolidone-iodine, PVP-I) as nasal spray. Procedures: Three groups received liposomal dispersion with PVP-I (2.2, 4.4 and 0% as control) in single and repeated use (3 days, three times a day). A set of functional and cytological tests as well as safety assessments were performed. Results: No safety-relevant finding or serious adverse events were reported, no evidence for cyto- nor genotoxicity obtained. No clinically relevant changes in mucosa appearance, nor in olfactory sense, nor in ciliary activity (sensitive indicator of local tolerance) occurred and no complaints about nasal airflow obstruction were observed. All liposomal formulations had a positive effect on the nasal mucosa, challenged by allergy in some volunteers. Conclusions and Message: Application of liposomal PVP-I spray to the nasal mucosa does not result in any demonstrable limitation of the nasal function nor in detectable damage to the multilayer ciliated epithelium of the nose. Improvement of various parameters of nasal function under liposomal PVP-I suggest improved mucociliary clearance. Explanation could be humidification, improved surfactant (phospholipid) level and/or sufficient mucolytic activity of iodide due to local application of the constituents.