Excess reserves and implementation of monetary policy of the ECB

This paper explains to what extent excess reserves are and should be relevant today in the implementation of monetary policy, focusing on the speci?c case of the operational framework of the Eurosystem. In particular, this paper studies the impact that changes to the operational framework for monetary policy implementation have on the level and volatility of excess reserves. A ‘transaction costs’ model that replicates the rather speci?c intra-reserve maintenance period pattern of excess reserves in the euro area is developed. Simulation results presented not only show that excess reserves may increase considerably under some changes to the operational framework, but also that their volatility and hence unpredictability could. JEL Classification: E52, E58excess reserves, liquidity management, monetary policy implementation

The Heavy Quark Potential from Wilson's Exact Renormalization Group

We perform a calculation of the full momentum dependence of the gluon and ghost propagators in pure SU(3) Yang-Mills theory by integrating Wilson's exact renormalization group equations with respect to an infrared cutoff k. The heavy quark potential in the quenched approximation can be expressed in terms of these propagators. Our results strongly indicate a 1/p^4 behaviour of the heavy quark potential for $p^2 \to 0$. We show in general, that effective actions which satisfy Schwinger-Dyson equations, correspond to (quasi-) fixed points of Wilson's exact renormalization group equations.Comment: 33 pages, 9 figs, (Comments on the compatibility of the approximations with BRST invariance have been added

Substellar companions and the formation of hot subdwarf stars

"Copyright 2011 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics."We give a brief review over the observational evidence for close substellar companions to hot subdwarf stars. The formation of these core helium-burning objects requires huge mass loss of their red giant progenitors. It has been suggested that besides stellar companions substellar objects in close orbits may be able to trigger this mass loss. Such objects can be easily detected around hot subdwarf stars by medium or high resolution spectroscopy with an RV accuracy at the km s(-1)-level. Eclipsing systems of Vir type stick out of transit surveys because of their characteristic light curves. The best evidence that substellar objects in close orbits around sdBs exist and that they are able to trigger the required mass loss is provided by the eclipsing system SDSS J0820+0008, which was found in the course of the MUCHFUSS project. Furthermore, several candidate systems have been discovered.Final Accepted Versio

Targeting PI3Kδ and PI3Kγ signalling disrupts human AML survival and bone marrow stromal cell mediated protection

Phosphoinositide-3-kinase (PI3K) is an enzyme group, known to regulate key survival pathways in acute myeloid leukaemia (AML). It generates phosphatidylinositol-3,4,5-triphosphate, which provides a membrane docking site for protein kinaseB activation. PI3K catalytic p110 subunits are divided into 4 isoforms; α,β,δ and γ. The PI3Kδ isoform is always expressed in AML cells, whereas the frequency of PI3Kγ expression is highly variable. The functions of these individual catalytic enzymes have not been fully resolved in AML, therefore using the PI3K p110δ and p110γ-targeted inhibitor IPI-145 (duvelisib) and specific p110δ and p110γ shRNA, we analysed the role of these two p110 subunits in human AML blast survival. The results show that PI3Kδ and PI3Kγ inhibition with IPI-145 has anti-proliferative activity in primary AML cells by inhibiting the activity of AKT and MAPK. Pre-treatment of AML cells with IPI-145 inhibits both adhesion and migration of AML blasts to bone marrow stromal cells. Using shRNA targeted to the individual isoforms we demonstrated that p110δ-knockdown had a more significant anti-proliferative effect on AML cells, whereas targeting p110γ-knockdown significantly inhibited AML migration. The results demonstrate that targeting both PI3Kδ and PI3Kγ to inhibit AML-BMSC interactions provides a biologic rationale for the pre-clinical evaluation of IPI-145 in AML

Nucleofection: A New Method for Cutaneous Gene Transfer?

Background. Transfection efficacy after nonviral gene transfer in primary epithelial cells is limited. The aim of this study was to compare transfection efficacy of the recently available method of nucleofection with the established transfection reagent FuGENE6. Methods. Primary human keratinocytes (HKC), primary human fibroblasts (HFB), and a human keratinocyte cell line (HaCaT) were transfected with reporter gene construct by FuGENE6 or Amaxa Nucleofector device. At corresponding time points, β-galactosidase expression, cell proliferation (MTT-Test), transduction efficiency (X-gal staining), cell morphology, and cytotoxicity (CASY) were determined. Results. Transgene expression after nucleofection was significantly higher in HKC and HFB and detected earlier (3 h vs. 24 h) than in FuGENE6. After lipofection 80%–90% of the cells remained proliferative without any influence on cell morphology. In contrast, nucleofection led to a decrease in keratinocyte cell size, with only 20%–42% proliferative cells. Conclusion. Related to the method-dependent increase of cytotoxicity, transgene expression after nucleofection was earlier and higher than after lipofection

Resource-Bound Quantification for Graph Transformation

Graph transformation has been used to model concurrent systems in software engineering, as well as in biochemistry and life sciences. The application of a transformation rule can be characterised algebraically as construction of a double-pushout (DPO) diagram in the category of graphs. We show how intuitionistic linear logic can be extended with resource-bound quantification, allowing for an implicit handling of the DPO conditions, and how resource logic can be used to reason about graph transformation systems

Evaluation of signal transduction pathways after transient cutaneous adenoviral gene delivery

<p>Abstract</p> <p>Background</p> <p>Adenoviral vectors have provided effective methods for <it>in vivo </it>gene delivery in therapeutic applications. However, these vectors can induce immune responses that may severely affect the ability of vector re-application. There is limited information about the mechanisms and signal transduction pathways involved in adenoviral recognition. For optimization of cutaneous gene therapy it is necessary to investigate molecular mechanisms of virus recognition in epidermal cells. The aim of this study was to investigate the signal transduction of the innate immunity after adenoviral DNA internalization in keratinocytes.</p> <p>Methods</p> <p><it>In vitro</it>, keratinocytes were transfected with DNA, in the presence and absence of inhibitors for signalling molecules. <it>In vivo</it>, immunocompetent and athymic mice (n = 3 per group) were twice transduced with an Ad-vector.</p> <p>Results</p> <p>The results show an acute induction of type-I-interferon after <it>in vitro </it>transfection. Inhibition of PI3K, p38 MAPK, JNK and NFkappaB resulted in a decreased expression of type-I-interferon. In contrast to immunocompetent mice, athymic mice demonstrated a constant transgene expression and reduced inflammatory response <it>in vivo</it>.</p> <p>Conclusion</p> <p>The results suggest an induction of the innate immunity triggered by cytoplasm localised DNA which is mediated by PI3K-, p38 MAPK-, JNK-, NFkappaB-, JAK/STAT- and ERK1/2-dependent pathways. A stable transgene expression and a reduced inflammatory response in immunodeficient mice have been observed. These results provide potential for an effective adenoviral gene delivery into immunosupressed skin.</p

A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate–mediated egress

Recent observations using multiphoton intravital microscopy (MP-IVM) have uncovered an unexpectedly high lymphocyte motility within peripheral lymph nodes (PLNs). Lymphocyte-expressed intracellular signaling molecules governing interstitial movement remain largely unknown. Here, we used MP-IVM of murine PLNs to examine interstitial motility of lymphocytes lacking the Rac guanine exchange factor DOCK2 and phosphoinositide-3-kinase (PI3K)γ, signaling molecules that act downstream of G protein–coupled receptors, including chemokine receptors (CKRs). T and B cells lacking DOCK2 alone or DOCK2 and PI3Kγ displayed markedly reduced motility inside T cell area and B cell follicle, respectively. Lack of PI3Kγ alone had no effect on migration velocity but resulted in increased turning angles of T cells. As lymphocyte egress from PLNs requires the sphingosine-1-phosphate (S1P) receptor 1, a Gαi protein–coupled receptor similar to CKR, we further analyzed whether DOCK2 and PI3Kγ contributed to S1P-triggered signaling events. S1P-induced cell migration was significantly reduced in T and B cells lacking DOCK2, whereas T cell–expressed PI3Kγ contributed to F-actin polymerization and protein kinase B phosphorylation but not migration. These findings correlated with delayed lymphocyte egress from PLNs in the absence of DOCK2 but not PI3Kγ, and a markedly reduced cell motility of DOCK2-deficient T cells in close proximity to efferent lymphatic vessels. In summary, our data support a central role for DOCK2, and to a lesser extent T cell–expressed PI3Kγ, for signal transduction during interstitial lymphocyte migration and S1P-mediated egress