Expansion Trees with Cut

Herbrand's theorem is one of the most fundamental insights in logic. From the syntactic point of view it suggests a compact representation of proofs in classical first- and higher-order logic by recording the information which instances have been chosen for which quantifiers, known in the literature as expansion trees. Such a representation is inherently analytic and hence corresponds to a cut-free sequent calculus proof. Recently several extensions of such proof representations to proofs with cut have been proposed. These extensions are based on graphical formalisms similar to proof nets and are limited to prenex formulas. In this paper we present a new approach that directly extends expansion trees by cuts and covers also non-prenex formulas. We describe a cut-elimination procedure for our expansion trees with cut that is based on the natural reduction steps. We prove that it is weakly normalizing using methods from the epsilon-calculus

Exploring Maintainability Assurance Research for Service- and Microservice-Based Systems: Directions and Differences

To ensure sustainable software maintenance and evolution, a diverse set of activities and concepts like metrics, change impact analysis, or antipattern detection can be used. Special maintainability assurance techniques have been proposed for service- and microservice-based systems, but it is difficult to get a comprehensive overview of this publication landscape. We therefore conducted a systematic literature review (SLR) to collect and categorize maintainability assurance approaches for service-oriented architecture (SOA) and microservices. Our search strategy led to the selection of 223 primary studies from 2007 to 2018 which we categorized with a threefold taxonomy: a) architectural (SOA, microservices, both), b) methodical (method or contribution of the study), and c) thematic (maintainability assurance subfield). We discuss the distribution among these categories and present different research directions as well as exemplary studies per thematic category. The primary finding of our SLR is that, while very few approaches have been suggested for microservices so far (24 of 223, ?11%), we identified several thematic categories where existing SOA techniques could be adapted for the maintainability assurance of microservices

Introducing Quantified Cuts in Logic with Equality

Cut-introduction is a technique for structuring and compressing formal proofs. In this paper we generalize our cut-introduction method for the introduction of quantified lemmas of the form $\forall x.A$ (for quantifier-free $A$) to a method generating lemmas of the form $\forall x_1\ldots\forall x_n.A$. Moreover, we extend the original method to predicate logic with equality. The new method was implemented and applied to the TSTP proof database. It is shown that the extension of the method to handle equality and quantifier-blocks leads to a substantial improvement of the old algorithm

A P-Functionalized [3]Ferrocenophane with a Dynamic SPS-Bridge

Ferrocene-1,1 '-dithiol reacts with PCl3 and P(NMe2)(3) to give [3]ferrocenophanes with SPS-ansa-bridges comprising potentially reactive P-Cl and P-N bonds at the central bridge atom. The products were characterized by NMR data and single-crystal XRD studies. The P-chloro-derivative exists both in the solid state and in solution as a mixture of two energetically nearly degenerate conformers with different stereochemical disposition of the ansa-bridge. Activation parameters for the dynamic equilibration between both isomers in solution were determined by dynamic NMR spectroscopy. Computational studies suggest that the isomerization proceeds via a torsional motion of the bridging SPS-unit rather than via configuration inversion at the phosphorus atom.Peer reviewe

Mechanism of angiotensin converting enzyme inhibitor-related anemia in renal transplant recipients

Mechanism of angiotensin converting enzyme inhibitor-related anemia in renal transplant recipients. To delineate the pathogenesis of the reduction in hemoglobin occurring in renal transplant patients treated with angiotensin converting enzyme inhibitors (ACEI) and azathioprine (AZA) a controlled, prospective trial of ACEI withdrawal was conducted. The ACEI was replaced by nifedipine or clonidine in 15 kidney transplant patients immunosuppressed with AZA and prednisone (enalapril in 14 and captopril in 1). Before and during 10 to 12 weeks after withdrawal of the ACEI, AZA metabolites, renal function parameters and hematological parameters including erythropoietin and reticulocytes were evaluated. Enalaprilat levels were measured and compared with 15 similar patients matched for transplant function and enalapril dosage immunosuppressed with cyclosporine and prednisone. AZA metabolites did not differ significantly in the presence or absence of the ACEI. Enalaprilat levels also showed no significant difference between the two patient groups treated with AZA or cyclosporine. Hematocrit and hemoglobin increased significantly from 37.5 ± 6.4 to 39.7 ± 3.6% (mean ± SD, P = 0.02) and 12.8 ± 2.2 to 13.5 ± 1.2 g/dl, P = 0.04, respectively, 10 to 12 weeks after ACEI treatment had been discontinued. Simultaneously numbers of reticulocytes and erythropoietin concentrations rose significantly after 2, 4 and 10 weeks, with a peak at two weeks (from 14.1 ± 3.8 to 20.6 ± 8.0%, P < 0.05 and from 14.3 ± 12.4 to 29.3 ± 54.5 mU/ml, P < 0.05, respectively). In conclusion, ACEI-related anemia in renal transplant recipients seems to be due to the erythropoietin-lowering effect of this group of drugs. A pharmacokinetic interaction between AZA and enalapril is not likely since plasma enalaprilat levels were independent of the immunosuppressive regimen and AZA metabolite levels were unchanged in the presence and absence of the ACEI. Several mechanisms by which angiotensin converting enzyme blockade may cause a decrease in circulating erythropoietin are discussed

VEGF-dependent induction of CD62E on endothelial cells mediates glioma tropism of adult haematopoietic progenitor cells

Haematopoietic progenitor cells (HPC) are attracted by experimental gliomas in vivo. This attraction is further enhanced by irradiation or hypoxic preconditioning of the glioma cells. Adhesive interactions might be critical to the preferential accumulation of HPC within the glioma tissue. Here, we studied the interactions of HPC with endothelial cells. Exposure of human cerebral endothelial cells (SV-HCEC), human microvascular endothelial cells (HMEC) and brain tumour endothelial cells derived from human glioblastomas (BTEC) to supernatants of glioma cells and primary glioma cells (SN-G) induced the expression of E-selectin (CD62E). CD62E expression was further enhanced when the glioma cells had been exposed to irradiation or hypoxia prior to the collection of supernatants, as well as by irradiation or exposure to hypoxia of the endothelial cells. Vascular cell adhesion molecule 1 (VCAM-1) was constitutively expressed on SV-HCEC, HMEC and BTEC, but was not modulated by SN-G, irradiation or hypoxia. Transendothelial HPC migration was enhanced after CD62E induction in vitro. Neutralizing antibodies to CD62E strongly reduced the homing of lin-Sca-1+c-kit+ cells to orthotopic SMA-560 gliomas in vivo. Tissue microarray sampling normal brain tissue and astrocytomas of WHO grades II-IV revealed a selective expression of CD62E on endothelial cells of tumour vessels. SN-G-induced CD62E expression on endothelial cells in vitro required transforming growth factor (TGF)-β signalling in glioma cells and vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGF-R2) signalling in endothelial cells. Further, we observed a nuclear factor kappa B-dependent activation of the CD62E promoter peaking at 12 h after VEGF-R2 activation by glioma-derived VEGF. Taken together, we identify glioma cell-induced CD62E expression on endothelial cells as one mediator of the glioma tropism of HP

Separate Universes Do Not Constrain Primordial Black Hole Formation

Carr and Hawking showed that the proper size of a spherical overdense region surrounded by a flat FRW universe cannot be arbitrarily large as otherwise the region would close up on itself and become a separate universe. From this result they derived a condition connecting size and density of the overdense region ensuring that it is part of our universe. Carr used this condition to obtain an upper bound for the density fluctuation amplitude with the property that for smaller amplitudes the formation of a primordial black hole is possible, while larger ones indicate a separate universe. In contrast, we find that the appearance of a maximum is not a consequence of avoiding separate universes but arises naturally from the geometry of the chosen slicing. Using instead of density a volume fluctuation variable reveals that a fluctuation is a separate universe iff this variable diverges on superhorizon scales. Hence Carr's and Hawking's condition does not pose a physical constraint on density fluctuations. The dynamics of primordial black hole formation with an initial curvature fluctuation amplitude larger than the one corresponding to the maximum density fluctuation amplitude was previously not considered in detail and so we compare it to the well-known case where the amplitude is smaller by presenting embedding and conformal diagrams of both types in dust spacetimes.Comment: Updated version corresponds to the published version 10.1103/PhysRevD.83.124025, 22 pages, 22 figure

Antagonism of the mammalian target of rapamycin selectively mediates metabolic effects of epidermal growth factor receptor inhibition and protects human malignant glioma cells from hypoxia-induced cell death

Although inhibition of the epidermal growth factor receptor is a plausible therapy for malignant gliomas that, in vitro, enhances apoptosis, the results of clinical trials have been disappointing. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that integrates starvation signals and generates adaptive responses that aim at the maintenance of energy homeostasis. Antagonism of mTOR has been suggested as a strategy to augment the efficacy of epidermal growth factor receptor inhibition by interfering with deregulated signalling cascades downstream of Akt. Here we compared effects of antagonism of mTOR utilizing rapamycin or a small hairpin RNA-mediated gene silencing to those of epidermal growth factor receptor inhibition or combined inhibition of epidermal growth factor receptor and mTOR in human malignant glioma cells. In contrast to epidermal growth factor receptor inhibition, mTOR antagonism neither induced cell death nor enhanced apoptosis induced by CD95 ligand or chemotherapeutic drugs. However, mTOR inhibition mimicked the hypoxia-protective effects of epidermal growth factor receptor inhibition by maintaining adenosine triphosphate levels. These in vitro experiments thus challenge the current view of mTOR as a downstream target of Akt that mediates antiapoptotic stimuli. Under the conditions of the tumour microenvironment, metabolic effects of inhibition of epidermal growth factor receptor, Akt and mTOR may adversely affect outcome by protecting the hypoxic tumour cell fractio