Chronic Graft versus Host Disease but not the Intensity of Conditioning has Impact on Survival after Allogeneic Hematopoietic Stem Cell Transplantation for Advanced Hematological Diseasess

Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is often performed in cases of advanced hematological diseases, but because of the associated mortality and a high risk of relapse it is life prolonging only in some patients. Patients and Methods: A retrospective multi-center analysis of 401 patients was conducted to analyze the variables associated with outcome after alloHSCT in advanced hematological diseases. The Cox proportional hazards model was used to assess the independence of overall survival (OS) and disease-free survival (DFS) from prognostic factors in a multivariate model. Results: The 5-year OS and DFS were 27.3 and 21.1% respectively. Multivariate analysis showed that the underlying malignancy had a significant influence on OS and DFS (p < 0.001 and p < 0.011, respectively), whereas development of severe acute graft versus host disease (GvHD) had a negative impact on OS (p < 0.001). Development of chronic GvHD showed a trend to a better OS (p = 0.085) and DFS (p = 0.199). No impact was seen for the intensity of conditioning. Conclusion: Development of chronic GvHD but not the conditioning regimen improved the outcome after alloHSCT for advanced malignancies, underlining the importance of immunological rather than cytotoxic effects

Double-plating of ovine critical sized defects of the tibia: a low morbidity model enabling continuous in vivo monitoring of bone healing

<p>Abstract</p> <p>Background</p> <p>Recent studies using sheep critical sized defect models to test tissue engineered products report high morbidity and complications rates. This study evaluates a large bone defect model in the sheep tibia, stabilized with two, a novel Carbon fibre Poly-ether-ether-ketone (CF-PEEK) and a locking compression plate (LCP) which could sustain duration for up to 6 month with an acceptable low complication rate.</p> <p>Methods</p> <p>A large bone defect of 3 cm was performed in the mid diaphysis of the right tibia in 33 sheep. The defect was stabilised with the CF - PEEK plate and an LCP. All sheep were supported with slings for 8 weeks after surgery. The study was carried out for 3 months in 6 and for 6 months in 27 animals.</p> <p>Results</p> <p>The surgical procedure could easily be performed in all sheep and continuous in vivo radiographic evaluation of the defect was possible. This long bone critical sized defect model shows with 6.1% a low rate of complications compared with numbers mentioned in the literature.</p> <p>Conclusions</p> <p>This experimental animal model could serve as a standard model in comparative research. A well defined standard model would reduce the number of experimental animals needed in future studies and would therefore add to ethical considerations.</p

Interleukin-6 receptor specific RNA aptamers for cargo delivery into target cells

Aptamers represent an emerging strategy to deliver cargo molecules, including dyes, drugs, proteins or even genes, into specific target cells. Upon binding to specific cell surface receptors aptamers can be internalized, for example by macropinocytosis or receptor mediated endocytosis. Here we report the in vitro selection and characterization of RNA aptamers with high affinity (Kd = 20 nM) and specificity for the human IL-6 receptor (IL-6R). Importantly, these aptamers trigger uptake without compromising the interaction of IL-6R with its natural ligands the cytokine IL-6 and glycoprotein 130 (gp130). We further optimized the aptamers to obtain a shortened, only 19-nt RNA oligonucleotide retaining all necessary characteristics for high affinity and selective recognition of IL-6R on cell surfaces. Upon incubation with IL-6R presenting cells this aptamer was rapidly internalized. Importantly, we could use our aptamer, to deliver bulky cargos, exemplified by fluorescently labeled streptavidin, into IL-6R presenting cells, thereby setting the stage for an aptamer-mediated escort of drug molecules to diseased cell populations or tissues

Solar cell process development in the european integrated project crystalclear

CrystalClear is a large integrated project funded by the European Commission that aims to drastically reduce the cost of crystalline Si PV modules, down to 1 Euro/Wp. Among the different subprojects, the one dealing with the development of advanced solar cells is relatively large (with 11 partners out of the 15 Crystal Clear partners taking part) and has a crucial role. The goal of the subproject is to develop cell design concepts and manufacturing processes that would enable a reduction in the order of 40% of the cell processing costs per Wp. In this paper, we give an overview of all the development work that has taken place in the CrystalClear solar cells subproject so far. World class results have been achieved, particularly on high efficiency cells on Si ribbons, and on industrial-type solar cells on very thin (120 (j.m thick) substrates

Green function techniques in the treatment of quantum transport at the molecular scale

The theoretical investigation of charge (and spin) transport at nanometer length scales requires the use of advanced and powerful techniques able to deal with the dynamical properties of the relevant physical systems, to explicitly include out-of-equilibrium situations typical for electrical/heat transport as well as to take into account interaction effects in a systematic way. Equilibrium Green function techniques and their extension to non-equilibrium situations via the Keldysh formalism build one of the pillars of current state-of-the-art approaches to quantum transport which have been implemented in both model Hamiltonian formulations and first-principle methodologies. We offer a tutorial overview of the applications of Green functions to deal with some fundamental aspects of charge transport at the nanoscale, mainly focusing on applications to model Hamiltonian formulations.Comment: Tutorial review, LaTeX, 129 pages, 41 figures, 300 references, submitted to Springer series "Lecture Notes in Physics

LRP1 Functions as an Atheroprotective Integrator of TGFβ and PDGF Signals in the Vascular Wall: Implications for Marfan Syndrome

BACKGROUND: The multifunctional receptor LRP1 controls expression, activity and trafficking of the PDGF receptor-β in vascular smooth muscle cells (VSMC). LRP1 is also a receptor for TGFβ1 and is required for TGFβ mediated inhibition of cell proliferation. METHODS AND PRINCIPAL FINDINGS: We show that loss of LRP1 in VSMC (smLRP(−)) in vivo results in a Marfan-like syndrome with nuclear accumulation of phosphorylated Smad2/3, disruption of elastic layers, tortuous aorta, and increased expression of the TGFβ target genes thrombospondin-1 (TSP1) and PDGFRβ in the vascular wall. Treatment of smLRP1(−) animals with the PPARγ agonist rosiglitazone abolished nuclear pSmad accumulation, reversed the Marfan-like phenotype, and markedly reduced smooth muscle proliferation, fibrosis and atherosclerosis independent of plasma cholesterol levels. CONCLUSIONS AND SIGNIFICANCE: Our findings are consistent with an activation of TGFβ signals in the LRP1-deficient vascular wall. LRP1 may function as an integrator of proliferative and anti-proliferative signals that control physiological mechanisms common to the pathogenesis of Marfan syndrome and atherosclerosis, and this is essential for maintaining vascular wall integrity

Identification and characterization of secreted and pathogenesis-related proteins in Ustilago maydis

Interactions between plants and fungal pathogens require a complex interplay at the plant–fungus interface. Extracellular effector proteins are thought to play a crucial role in establishing a successful infection. To identify pathogenesis-related proteins in Ustilago maydis we combined the isolation of secreted proteins using a signal sequence trap approach with bioinformatic analyses and the subsequent characterization of knock-out mutants. We identified 29 secreted proteins including hydrophobins and proteins with a repetitive structure similar to the repellent protein Rep1. Hum3, a protein containing both, a hydrophobin domain and a repetitive Rep1-like region, is shown to be processed during passage through the secretory pathway. While single knock-outs of hydrophobin or repellent-like genes did not affect pathogenicity, we found a strong effect of a double knock-out of hum3 and the repetitive rsp1. Yeast-like growth, mating, aerial hyphae formation and surface hydrophobicity were unaffected in this double mutant. However, pathogenic development in planta stops early after penetration leading to a complete loss of pathogenicity. This indicates that Hum3 and Rsp1 are pathogenicity proteins that share an essential function in early stages of the infection. Our results demonstrate that focusing on secreted proteins is a promising way to discover novel pathogenicity proteins that might be broadly applied to a variety of fungal pathogens