Opposition to capital market opening

We employ a neoclassical growth model to assess the impact of financial liberalization in a developing country on capital owners` and workers` consumption and welfare. We find in a baseline calibration for an average non-OECD country that capitalists suffer a 42 percent reduction in permanent consumption because capital inflows reduce their return to capital while workers gain 8 percent of permanent consumption because capital inflows increase wages. These huge gross impacts contrast with the small positive net effect found in a neoclassical represent agent model by Gourinchas and Jeanne (2006). We further show that the result for capitalists is insensitive to enhanced productivity catch-up processes induced by capital inflows. Our findings can help explain why poorer countries tend to be less financially open as capitalists` losses are largest for countries with the lowest capital stocks, inducing strong opposition to capital market opening. --Capital flows,international financial integration,growth,neoclassical model,heterogenous agents

Education policy networks in a comparative perspective: Germany, Switzerland, Great Britain and New Zealand

International initiatives in education, such as PISA and the Bologna Process, have distinctly changed conditions framing domestic policy-making. This paper sheds light on the territorial and modal dispersion of national education policy networks by means of a systematic network analytical description. The focus is on changing patterns of interactions and coalitions between international and national as well as private and public actors. Therefore, we analyse four countries, i.e. Germany, Switzerland, Great Britain and New Zealand, in a comparative perspective. The findings show that in most countries there is indeed an internationalization of education politics taking place in the sense of an increasing participation of international actors. These actors apply a more and more diversified portfolio of governance instruments. At the same time, however, domestic veto players develop a rich set of strategies to cope, compete or collaborate with international actors. -- Internationale Initiativen, wie z.B. der Bologna Prozess oder die PISA-Studien, haben die Rahmenbedingungen nationaler Bildungspolitik grundlegend verändert. In diesem Arbeitspapier wird die Internationalisierung von Bildungspolitik aus netzwerkanalytischer Perspektive beleuchtet. Ziel ist es, den Wandel von Formen politischer Interaktion und Koalitionen zwischen internationalen und nationalen sowie privaten und öffentlichen Akteuren zu beschreiben. Dazu werden Politiknetzwerke in vier Ländern - Deutschland, Schweiz, Großbritannien und Neuseeland - vergleichend analysiert. Anhand der Befunde lässt sich eine Internationalisierung des Politikfelds Bildung erkennen, d.h. internationale Akteure treten im Kontext nationaler politischer Interaktion zunehmend in Erscheinung. Gleichzeitig zeigt sich, dass auch nationale Vetospieler Strategien entwickeln, um dieser neuen Konstellation in der Bildungspolitik zu begegnen.

Simple Modifications of Branched PEI Lead to Highly Efficient siRNA Carriers with Low Toxicity

Polymer carriers like PEI which proved their efficiency in DNA delivery were found to be far less effective for the applications with siRNA. In the current study, we generated a number of nontoxic derivates of branched PEI through modification of amines by ethyl acrylate, acetylation of primary amines, or introduction of negatively charged propionic acid or succinic acid groups to the polymer structure. The resulting products showed high efficiency in siRNA-mediated knockdown of target gene. In particular, succinylation of branched PEI resulted in up to 10-fold lower polymer toxicity in comparison to unmodified PEI. Formulations of siRNA with succinylated PEI were able to induce remarkable knockdown (80% relative to untreated cells) of target luciferase gene at the lowest tested siRNA concentration of 50 nM in Neuro2ALuc cells. The polyplex stability assay revealed that the efficiency of formulations which are stable in physiological saline is independent of the affinity of siRNA to the polymer chain. The improved properties of modified PEI as siRNA carrier are largely a consequence of the lower polymer toxicity. In order to achieve significant knockdown of target gene, the PEI-based polymer has to be applied at higher concentrations, required most probably for sufficient accumulation and proton sponge effects in endosomes. Unmodified PEI is highly toxic at such polymer concentrations. In contrast, the far less toxic modified analogues can be applied in concentrations required for the knockdown of target genes without side effects

Frei zirkulierende methylierte DNA als Tumormarker des kolorektalen Karzinoms

Ziel der Studien war die Untersuchung der prognostischen Aussagekraft der methylierten Gene HLTF, HPP1 und NEUROG1. Bislang wird eine Prognoseabschätzung hauptsächlich über radiologische und pathologische Kriterien erreicht. Im Blut bestimmte Marker haben den Vorteil einer relativ unaufwändigen, nichtinvasiven Gewinnung und könnten eine wertvolle Ergänzung der etablierten Faktoren darstellen. Als Vergleichsmarker wurde mit dem CEA der einzige für das KRK relevante Tumormarker, für den eine prognostische Wertigkeit beschrieben wurde, gewählt. Anhand der vorliegenden Daten konnte gezeigt werden, dass HLTF- und HPP1-Methylierung am häufigsten im Serum von Patienten mit fortgeschrittenen, insbesondere metastasierten, Erkrankungen zu finden sind und Marker für eine deutlich schlechtere Prognose sind. Dieser hochsignifikante Effekt zeigte sich insbesondere bei den Patienten mit Metastasen, bei denen jeweils eine Subgruppe mit einer deutlich schlechteren Prognose identifiziert werden konnte. Im Vergleich mit CEA zeigten HLTF und HPP1 eine mindestens gleichwertige prognostische Bedeutung im vorliegenden Kollektiv. Auch in der multivariaten Analyse blieben HLTF, HPP1 und CEA als voneinander unabhängige prognostische Faktoren im Stadium IV bestehen, wobei der Vorteil von HLTF und HPP1 darin liegt, dass diese weiter als binäre Parameter verwendet werden können, während für CEA erst ein passender Grenzwert innerhalb der Population definiert werden muss. Das Vorliegen von korrespondierenden Gewebeproben zu den untersuchten Blutproben ermöglichte die erstmalige Untersuchung der Korrelation von Methylierung von HLTF, HPP1 und NEUROG1 in Serum und Primärtumor. Alle positiven Serumproben zeigten bis auf eine Ausnahme auch Methylierung der entsprechenden Gene im Gewebe. Damit konnte diese Untersuchung die angenommene Herkunft der frei zirkulierenden methylierenden DNA aus dem Tumor bestätigen. Ein Zusammenhang mit dem Methylierungsphänotyp CIMP ergab sich im Kollektiv nicht. In einer weiteren Untersuchung wurde der Zusammenhang der drei Zielparameter mit LDH im Blut als Surrogatmarker für einen hohen Zellzerfall untersucht. Die hohe Korrelation von HLTF und HPP1 mit erhöhten LDH-Spiegeln legt den Zerfall der Tumorzellen als möglichen Mechanismus der Freisetzung der Tumor-DNA in die Blutbahn nahe. Auf der anderen Seite bestand kein Zusammenhang von LDH und Methylierung von NEUROG1. Somit müssen neben tumorassoziiertem Zelltod weitere Mechanismen bei der Freisetzung von methylierter Tumor-DNA eine Rolle spielen, die aktuell noch ungeklärt sind. Zusammenfassend wurde frei zirkulierende methylierte HLTF- und HPP1-DNA als unabhängiger prognostischer Marker des metastasierten kolorektalen Karzinoms untersucht und charakterisiert. Diese vielversprechenden Ergebnisse stellen wertvolle Ansatzpunkte für die weitere Erforschung der Marker in Folgestudien dar, um klinische Anwendungsgebiete zu evaluieren, beispielsweise in der prätherapeutischen Risikostratifizierung, im Therapiemonitoring oder auch zur Prädiktion des Ansprechens auf spezifische Tumortherapien.The aim of these studies was to evaluate the prognostic value of methylated genes HLTF, HPP1, and NEUROG1. To date, the assessment of prognosis was typically done via radiological or pathological criteria. The significant advantage of blood-based markers lies in the relatively easy, non-invasive retrieval and could therefore prove a useful addition to the established markers. CEA was chosen as a comparative tumor marker for being, until now, the only one with a proven prognostic relevance for colorectal carcinoma. The conducted measurements demonstrated that methylated DNA of HLTF and HPP1 genes was found more frequently in blood samples of patients with advanced, and specifically, metastasized colorectal cancer (CRC) and is a marker for worse prognosis. This highly significant effect appeared specifically among the group of patients with metastases, within which a subgroup with a notably worse prognosis could be identified. Compared with CEA, the prognostic relevance of HLTF and HPP1 was at least equal in the collective studied. Likewise, in multivariate analysis HLTF, HPP1 and CEA remained independent prognostic factors in stage IV, the advantage of HLTF and HPP1 being that these markers can continue to be used as binary parameters, whereas a suitable cutoff value for CEA within the population needs to be defined first. The availability of tissue samples corresponding to the examined blood samples allowed for the first study of the correlation between methylation of HLTF, HPP1 and NEUROG1 in serum and primary tumor. All positive serum samples, with one exception, also showed methylation of the respective genes in the tissue samples. Hence this study was able to confirm the hypothesized provenance of circulating cell-free methylated DNA from the tumor. An interrelation with methylation phenotype CIMP was not evident in the study population. In a subsequent study the correlation of the three target parameters with LDH in blood as a surrogate marker for cell disintegration was examined. The high correlation of HLTF and HPP1 with elevated LDH levels suggests the decomposition of tumor cells as a possible mechanism by which tumor DNA is released into the bloodstream. On the other hand, no correlation between LDH and methylation of NEUROG1 existed. Therefore mechanisms other than tumor associated cell death have to play a role in the release of methylated tumor DNA, which are unexplained yet. In summary, methylated circulating cell-free HLTF and HPP1 DNA was analyzed and characterized as an independent prognostic marker for metastasized CRC. The promising results provide valuable groundwork for further examination of these markers in subsequent studies in order to evaluate potential clinical use for example in pretherapeutic risk stratification, therapy monitoring or prediction of response to specific tumor therapies

On high-order pressure-robust space discretisations, their advantages for incompressible high Reynolds number generalised Beltrami flows and beyond

An improved understanding of the divergence-free constraint for the incompressible Navier--Stokes equations leads to the observation that a semi-norm and corresponding equivalence classes of forces are fundamental for their nonlinear dynamics. The recent concept of {\em pressure-robustness} allows to distinguish between space discretisations that discretise these equivalence classes appropriately or not. This contribution compares the accuracy of pressure-robust and non-pressure-robust space discretisations for transient high Reynolds number flows, starting from the observation that in generalised Beltrami flows the nonlinear convection term is balanced by a strong pressure gradient. Then, pressure-robust methods are shown to outperform comparable non-pressure-robust space discretisations. Indeed, pressure-robust methods of formal order $k$ are comparably accurate than non-pressure-robust methods of formal order $2k$ on coarse meshes. Investigating the material derivative of incompressible Euler flows, it is conjectured that strong pressure gradients are typical for non-trivial high Reynolds number flows. Connections to vortex-dominated flows are established. Thus, pressure-robustness appears to be a prerequisite for accurate incompressible flow solvers at high Reynolds numbers. The arguments are supported by numerical analysis and numerical experiments.Comment: 43 pages, 18 figures, 2 table

Breathing Life into Polycations

The lack of efficient delivery systems is still limiting the full therapeutic potential of siRNA. For the purpose of nucleic acid transfer, among other synthetic carrier systems, polycations have been applied. Favorable characteristics of suitable polymers include nucleic acid binding, compaction, protection, and biocompatibility. However the lack of nucleic acid transfer activity in transfection-based screening often abandons promising candidates. Here we present that functionalization may turn polycations with poor delivery activity into efficient carriers:  for example, polylysine, on its own lacking nucleic acid transfer activity, displayed high efficiency in siRNA delivery after modification with polyethylene glycol and a pH-responsive endosomolytic peptide. Hence these findings have implication for the selection process of polymeric carriers for siRNA