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The European Commission recently put forward a proposal for a regulation to amend and strengthen the 2009 version of the EU's rules on the regulation of credit rating agencies ("CRA3"). Among other things, Art. 35a of the draft proposal introduces strict liability for rating agencies. This liability proposal is at odds with the aim to strengthen competition in the rating sector and could have a chilling effect on capital markets. The paper analyses existing rules on civil liability of rating agencies under different legal systems. Subsequently, the provision under Art. 35a of the Draft Proposal is examinded more closely. Suggestions on possible improvemts of the proposal are made.
SAFE Newsletter : 2013, Q1
(2013)
Debt-induced crises, including the subprime, are usually attributed exclusively to supply-side factors. We uncover an additional factor contributing to debt culture, namely social influences emanating from the perceived average income of peers. Using unique information from a representative household survey of the Dutch population that circumvents the need to define the social circle, we consider collateralized, consumer, and informal loans. We find robust social effects on borrowing – especially among those who consider themselves poorer than their peers – and on indebtedness, suggesting a link to financial distress. We check the robustness of our results using several approaches to rule out spurious associations and handle correlated effects.
Planar cell polarity (PCP)–the coordinated polarisation of a whole field of cells within the plane of a tissue–relies on the interaction of three modules: a global module that couples individual cellular polarity to the tissue axis, a local module that aligns the axis of polarisation of neighbouring cells, and a readout module that directs the correct outgrowth of PCP-regulated structures such as hairs and bristles. While much is known about the molecular components that are required for PCP, the functional details of–and interactions between–the modules remain unclear. In this work, we perform a mathematical and computational analysis of two previously proposed computational models of the local module (Amonlirdviman et al., Science, 307, 2005; Le Garrec et al., Dev. Dyn., 235, 2006). Both models can reproduce wild-type and mutant phenotypes of PCP observed in the Drosophila wing under the assumption that a tissue-wide polarity cue from the global module persists throughout the development of PCP. We demonstrate that both models can also generate tissue-level PCP when provided with only a transient initial polarity cue. However, in these models such transient cues are not sufficient to ensure robustness of the resulting cellular polarisation.
Since the 1980s, advances in wastewater treatment technology have led to considerably improved surface water quality in the urban areas of many high income countries. However, trace concentrations of organic wastewater-associated contaminants may still pose a key environmental hazard impairing the ecological quality of surface waters. To identify key impact factors, we analyzed the effects of a wide range of anthropogenic and environmental variables on the aquatic macroinvertebrate community. We assessed ecological water quality at 26 sampling sites in four urban German lowland river systems with a 0–100% load of state-of-the-art biological activated sludge treated wastewater. The chemical analysis suite comprised 12 organic contaminants (five phosphor organic flame retardants, two musk fragrances, bisphenol A, nonylphenol, octylphenol, diethyltoluamide, terbutryn), 16 polycyclic aromatic hydrocarbons, and 12 heavy metals. Non-metric multidimensional scaling identified organic contaminants that are mainly wastewater-associated (i.e., phosphor organic flame retardants, musk fragrances, and diethyltoluamide) as a major impact variable on macroinvertebrate species composition. The structural degradation of streams was also identified as a significant factor. Multiple linear regression models revealed a significant impact of organic contaminants on invertebrate populations, in particular on Ephemeroptera, Plecoptera, and Trichoptera species. Spearman rank correlation analyses confirmed wastewater-associated organic contaminants as the most significant variable negatively impacting the biodiversity of sensitive macroinvertebrate species. In addition to increased aquatic pollution with organic contaminants, a greater wastewater fraction was accompanied by a slight decrease in oxygen concentration and an increase in salinity. This study highlights the importance of reducing the wastewater-associated impact on surface waters. For aquatic ecosystems in urban areas this would lead to: (i) improvement of the ecological integrity, (ii) reduction of biodiversity loss, and (iii) faster achievement of objectives of legislative requirements, e.g., the European Water Framework Directive.
This study indicates that embryonic stem cells [ESCs] cultured with retinoic acid and activin A significantly upregulate the miRNA let-7e. This specific miRNA modulates the Wnt pathway and the expression of early nephrogenic markers under these differentiation conditions. The differentiation markers WT1, Pax2 and Wnt4 were downregulated when miRNA let-7e was silenced, thus indicating the role of miRNA let-7e in the differentiation process. PKCβ, GSK3β phosphorylation (GSK3βP) and β-catenin expression was reduced in differentiated cells and reversed by miRNA let-7e silencing. Addition of a PKCβ inhibitor to the miRNA let-7e silenced cells abolished let-7e-derived effects in differentiation markers, and reversed the increase in GSK3βP and β-catenin, thus indicating that miRNA let-7e is involved in differentiation via the modulation of GSK3β phosphorylation and β-catenin production.
Die Dissertation stellt das Machtgeflecht in der Islamischen Stadt Marawi City (Mindanao, Philippinen) dar, in die die dortigen Gender-Debatten involviert sind. In einer Umgebung, die als Konsequenz des Mindanao Konfliktes als “no war, no peace”-Umgebung definiert werden kann, gibt es drei Hauptdarsteller: die nationale Regierung des mehrheitlich christlichen Staates der Philippinen (GRP), die Autonome Regierung im Muslimischen Mindanao (ARMM), zu der auch Marawi City zählt, und die islamische Rebellengruppe Moro Islamic Liberation Front (MILF), die einen islamischen (unter-)Staat fordert. Die GRP unterstützt Re-Islamisierungs- und Re-Traditionalisierungsbewegungen in der ARMM, um die Opposition zur MILF zu stärken. Die Konsequenz ist jedoch keine Kollaboration zwischen der GRP und der ARMM. Stattdessen nutzen Politiker ihre Privilegien aus, um ihren eigenen Absichten zu folgen. Sei dies, um politische Gegner auszuspielen oder das traditionelle Sultanatssystem zu fördern. Für Gender-Debatten gibt es in diesem Kontext der ungelösten nationalen Frage kaum Spielraum außerhalb einer Islamischen Narrative; dies bedeutet jedoch nicht, dass Gender nicht debattiert wird, sondern, dass die Debatten inner-Islamisch sind, hauptsächlich zwischen Repräsentanten des traditionell synkretistischen Islam und Vertretern Islamischer Revitalisierungsbewegungen. Speziell erstere erscheinen sehr einflussreich bezüglich Gender Strategien in der Region. Dies ist nur teilweise auf die Unterstützung der nationalen Regierung zurückzuführen, sondern ist vor allem eine Frage von Identität. Diese wiederum wird nicht vorranging über Religion, sondern nach ethnischen Maßstäben und im Speziellen im Rahmen von Clanstrukturen definiert.
Orthotopic bladder cancer xenografts are essential for testing novel therapies and molecular manipulations of cell lines in vivo. Current xenografts rely on tumor cell inoculation by intravesical instillation or direct injection into the bladder wall. Instillation is limited by the lack of cell lines that are tumorigenic when delivered in this manner. The invasive model inflicts morbidity on the mice by the need for laparotomy and mobilization of the bladder. Furthermore this procedure is complex and time-consuming. Three bladder cancer cell lines (UM-UC1, UM-UC3, UM-UC13) were inoculated into 50 athymic nude mice by percutaneous injection under ultrasound guidance. PBS was first injected between the muscle wall and the mucosa to separate these layers, and tumor cells were subsequently injected into this space. Bioluminescence and ultrasound were used to monitor tumor growth. Contrast-enhanced ultrasound was used to study changes in tumor perfusion after systemic gemcitabine/cisplatin treatment. To demonstrate proof of principle that therapeutic agents can be injected into established xenografts under ultrasound guidance, oncolytic virus (VSV) was injected into UM-UC3 tumors. Xenograft tissue was harvested for immunohistochemistry after 23–37 days. Percutaneous injection of tumor cells into the bladder wall was performed efficiently (mean time: 5.7 min) and without complications in all 50 animals. Ultrasound and bioluminescence confirmed presence of tumor in the anterior bladder wall in all animals 3 days later. The average tumor volumes increased steadily over the study period. UM-UC13 tumors showed a marked decrease in volume and perfusion after chemotherapy. Immunohistochemical staining for VSV-G demonstrated virus uptake in all UM-UC3 tumors after intratumoral injection. We have developed a novel method for creating orthotopic bladder cancer xenograft in a minimally invasive fashion. In our hands this has replaced the traditional model requiring laparotomy, because this model is more time efficient, more precise and associated with less morbidity for the mice.
Natural killer (NK) cells are highly specialized effectors of the innate immune system that hold promise for adoptive cancer immunotherapy. Their cell killing activity is primarily mediated by the pro-apoptotic serine protease granzyme B (GrB), which enters targets cells with the help of the pore-forming protein perforin. We investigated expression of a chimeric GrB fusion protein in NK cells as a means to augment their antitumoral activity. For selective targeting to tumor cells, we fused the epidermal growth factor receptor (EGFR) peptide ligand transforming growth factor α (TGFα) to human pre-pro-GrB. Established human NKL natural killer cells transduced with a lentiviral vector expressed this GrB-TGFα (GrB-T) molecule in amounts comparable to endogenous wildtype GrB. Activation of the genetically modified NK cells by cognate target cells resulted in the release of GrB-T together with endogenous granzymes and perforin, which augmented the effector cells' natural cytotoxicity against NK-sensitive tumor cells. Likewise, GrB-T was released into the extracellular space upon induction of degranulation with PMA and ionomycin. Secreted GrB-T fusion protein displayed specific binding to EGFR-overexpressing tumor cells, enzymatic activity, and selective target cell killing in the presence of an endosomolytic activity. Our data demonstrate that ectopic expression of a targeted GrB fusion protein in NK cells is feasible and can enhance antitumoral activity of the effector cells.
Despite numerous large-scale phylogenomic studies, certain parts of the mammalian tree are extraordinarily difficult to resolve. We used the coding regions from 19 completely sequenced genomes to study the relationships within the super-clade Euarchontoglires (Primates, Rodentia, Lagomorpha, Dermoptera and Scandentia) because the placement of Scandentia within this clade is controversial. The difficulty in resolving this issue is due to the short time spans between the early divergences of Euarchontoglires, which may cause incongruent gene trees. The conflict in the data can be depicted by network analyses and the contentious relationships are best reconstructed by coalescent-based analyses. This method is expected to be superior to analyses of concatenated data in reconstructing a species tree from numerous gene trees. The total concatenated dataset used to study the relationships in this group comprises 5,875 protein-coding genes (9,799,170 nucleotides) from all orders except Dermoptera (flying lemurs). Reconstruction of the species tree from 1,006 gene trees using coalescent models placed Scandentia as sister group to the primates, which is in agreement with maximum likelihood analyses of concatenated nucleotide sequence data. Additionally, both analytical approaches favoured the Tarsier to be sister taxon to Anthropoidea, thus belonging to the Haplorrhine clade. When divergence times are short such as in radiations over periods of a few million years, even genome scale analyses struggle to resolve phylogenetic relationships. On these short branches processes such as incomplete lineage sorting and possibly hybridization occur and make it preferable to base phylogenomic analyses on coalescent methods.
Neuronal activity differs between wakefulness and sleep states. In contrast, an attractor state, called self-organized critical (SOC), was proposed to govern brain dynamics because it allows for optimal information coding. But is the human brain SOC for each vigilance state despite the variations in neuronal dynamics? We characterized neuronal avalanches – spatiotemporal waves of enhanced activity - from dense intracranial depth recordings in humans. We showed that avalanche distributions closely follow a power law – the hallmark feature of SOC - for each vigilance state. However, avalanches clearly differ with vigilance states: slow wave sleep (SWS) shows large avalanches, wakefulness intermediate, and rapid eye movement (REM) sleep small ones. Our SOC model, together with the data, suggested first that the differences are mediated by global but tiny changes in synaptic strength, and second, that the changes with vigilance states reflect small deviations from criticality to the subcritical regime, implying that the human brain does not operate at criticality proper but close to SOC. Independent of criticality, the analysis confirms that SWS shows increased correlations between cortical areas, and reveals that REM sleep shows more fragmented cortical dynamics.
Bücher und Zeitschriften, aber auch weitere Materialien wie Zeitungen, Notendrucke, Autographen und anderes gehören seit Jahrhunderten zum Bestand wissenschaftlicher Bibliotheken und sind gleichzeitig Objekte für Lehre und Forschung. Sie zu sammeln, zu erschließen und den Interessierten zugänglich zu machen, war und ist die Aufgabe von Bibliotheken. Nun befinden wir uns heute jedoch in einer Zeit des fundamentalen Wandels. Von Vielen wird er als Paradigma beschrieben, welches dadurch gekennzeichnet ist, dass die Welt der gedruckten Texte und Bilder (Gutenberg-Galaxis) abgelöst wird von einer digitalen Welt (Turing-Galaxis), in der Information nicht mehr an einen und schon gar nicht analogen Träger gebunden ist. In der Folge der Entwicklung des Internets sind in den letzten zwei Jahrzehnten mit Suchmaschinen und "Discovery Systemen", mit elektronischen Zeitschriften und ebensolchen Büchern, mit Hypertexten und dem "Semantic Web" Strukturen entstanden, denen eines gemeinsam ist. Ihre informationellen Inhalte sind nicht mehr an ein physisches Objekt gebunden, sie sind nicht mehr lokalisierbar und von daher im Prinzip von überall her und zu jeder Zeit nutzbar. ...
Paging is one of the prominent problems in the field of on-line algorithms. While in the deterministic setting there exist simple and efficient strongly competitive algorithms, in the randomized setting a tradeoff between competitiveness and memory is still not settled. Bein et al. [4] conjectured that there exist strongly competitive randomized paging algorithms, using o(k) bookmarks, i.e. pages not in cache that the algorithm keeps track of. Also in [4] the first algorithm using O(k) bookmarks (2k more precisely), Equitable2, was introduced, proving in the affirmative a conjecture in [7].
We prove tighter bounds for Equitable2, showing that it requires less than k bookmarks, more precisely ≈ 0.62k. We then give a lower bound for Equitable2 showing that it cannot both be strongly competitive and use o(k) bookmarks. Nonetheless, we show that it can trade competitiveness for space. More precisely, if its competitive ratio is allowed to be (Hk + t), then it requires k/(1 + t) bookmarks.
Our main result proves the conjecture that there exist strongly competitive paging algorithms using o(k) bookmarks. We propose an algorithm, denoted Partition2, which is a variant of the Partition algorithm byMcGeoch and Sleator [13]. While classical Partition is unbounded in its space requirements, Partition2 uses θ(k/ log k) bookmarks. Furthermore, we show that this result is asymptotically tight when the forgiveness steps are deterministic.
Recht und die Vorstellung von dem, was Recht ist, sind nicht allein an Territorien oder Herrschaften gebunden, sondern wandern mit den Menschen mit. Treffen mehrere möglicherweise anwendbare Rechte aufeinander, steht für heutige Gerichte ein Kollisionsrecht wie das Internationale Privatrecht bereit, dass über den Umgang mit diesem Konflikt entscheidet , indem es den Fall einer bestimmten nationalstaatlichen Regelung unterstellt. Andere Lösungen sind jedoch ebenfalls denkbar und wurden in der Vergangenheit auch praktiziert, was heute schwer nachzuvollziehen ist. Um die Denkstruktur und Grenzen der modernen Herangehensweise deutlich werden zu lassen, sollen in diesem Beitrag die Schwierigkeiten erläutert werden, das Konzept des Internationalen Privatrechts auf das Neben- und Miteinander verschiedener rechtlicher Traditionen im hellenistischen Ägypten zu übertragen. Ziel ist es, auch Nichtjuristen damit einen Einstieg und eine Übersicht über die Diskussion innerhalb der antiken Rechtsgeschichte zu ermöglichen.
This thesis presents various algorithms which have been developed for on-line event reconstruction in the CBM experiment at GSI, Darmstadt and the ALICE experiment at CERN, Geneve. Despite the fact that the experiments are different — CBM is a fixed target experiment with forward geometry, while ALICE has a typical collider geometry — they share common aspects when reconstruction is concerned.
The thesis describes:
— general modifications to the Kalman filter method, which allows one to accelerate, to improve, and to simplify existing fit algorithms;
— developed algorithms for track fit in CBM and ALICE experiment, including a new method for track extrapolation in non-homogeneous magnetic field.
— developed algorithms for primary and secondary vertex fit in the both experiments. In particular, a new method of reconstruction of decayed particles is presented.
— developed parallel algorithm for the on-line tracking in the CBM experiment.
— developed parallel algorithm for the on-line tracking in High Level Trigger of the ALICE experiment.
— the realisation of the track finders on modern hardware, such as SIMD CPU registers and GPU accelerators.
All the presented methods have been developed by or with the direct participation of the author.