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Background and Purpose. Leukocyte migration into alveolar space plays a critical role in pulmonary inflammation resulting in lung injury. Acute ethanol (EtOH) exposure exerts anti-inflammatory effects. The clinical use of EtOH is critical due to its side effects. Here, we compared effects of EtOH and ethyl pyruvate (EtP) on neutrophil adhesion and activation of cultured alveolar epithelial cells (A549). Experimental Approach. Time course and dose-dependent release of interleukin- (IL-) 6 and IL-8 from A549 were measured after pretreatment of A549 with EtP (2.5–10 mM), sodium pyruvate (NaP, 10 mM), or EtOH (85–170 mM), and subsequent lipopolysaccharide or IL-1beta stimulation. Neutrophil adhesion to pretreated and stimulated A549 monolayers and CD54 surface expression were determined. Key Results. Treating A549 with EtOH or EtP reduced substantially the cytokine-induced release of IL-8 and IL-6. EtOH and EtP (but not NaP) reduced the adhesion of neutrophils to monolayers in a dose- and time-dependent fashion. CD54 expression on A549 decreased after EtOH or EtP treatment before IL-1beta stimulation. Conclusions and Implications. EtP reduces secretory and adhesive potential of lung epithelial cells under inflammatory conditions. These findings suggest EtP as a potential treatment alternative that mimics the anti-inflammatory effects of EtOH in early inflammatory response in lungs.
The highly conserved eukaryotic process of macroautophagy (autophagy) is a non-specific bulk-degradation program critical for maintaining proper cellular homeostasis, and for clearing aged and damaged organelles. This decision is inextricably dependent upon prevailing metabolic demands and energy requirements of the cell. Soluble monomeric decorin functions as a natural tumor repressor that antagonizes a variety of receptor tyrosine kinases. Recently, we discovered that decorin induces endothelial cell autophagy, downstream of VEGFR2. This process was wholly dependent upon Peg3, a decorin-inducible genomically imprinted tumor suppressor gene. However, the signaling cascades responsible have remained elusive. In this report we discovered that Vps34, a class III phosphoinositide kinase, is an upstream kinase required for Peg3 induction. Moreover, decorin triggered differential formation of Vps34/Beclin 1 complexes with concomitant dissolution of inhibitive Bcl-2/Beclin 1 complexes. Further, decorin inhibited anti-autophagic signaling via suppression of Akt/mTOR/p70S6K activity with the concurrent activation of pro-autophagic AMPK-mediated signaling cascades. Mechanistically, AMPK is downstream of VEGFR2 and inhibition of AMPK signaling abrogated decorin-evoked autophagy. Collectively, these findings hint at the complexity of the underlying molecular relays necessary for decorin-evoked endothelial cell autophagy and reveal important therapeutic targets for augmenting autophagy and combatting tumor angiogenesis.
Sparse sensor networks for Lamb wave-based structural health monitoring (SHM) can detect defects in plate-like structures. However, the limited number of sensor positions provides little information to characterize the unknown scatterer. This can be achieved by full wavefield analysis e.g. using Laser Doppler vibrometry measurements.
This paper proposes deconvolution processing that enhances the acoustic wavefield interpretation by increasing the temporal resolution of the underlying ultrasound signals. Applying this preprocessor to the whole wavefield allows improved non-destructive assessment of the defect. This approach is verified experimentally through a case study on an isotropic aluminum plate with four cracks.
Decomposing coordination
(2014)
Natural languages display a surprising diversity of expression of elementary logical operations. The study of this variation is emerging as an important topic of cross-linguistic semantics. In this paper, we address the expression of coordination from this perspective, especially coordination of individual denoting expressions such as "John and Mary". We argue that there is an underlying universal structure for individual coordination, and that the cross-linguistic variation can be explained by assuming that languages pronounce different morphemes of this universal structure. In particular, we argue that there two main types of system for the expression of individual coordination: the J-type and the μ-type. In μ-type languages the morpheme used for individual coordination also has uses a quantificational or focus particle, while in the J-type languages it doesn't. Instead at least in many J-type languages the same morpheme is used for individual and propositional coordination. The evidence we present for our model comes from two sources: new data from specific data of the J-type and μ-type languages, and from a study of the historical development of the expression of individual coordination in Indo-European which switched from a μ-type to a J-type system.
We enlarge the so-called extended linear Sigma model (eLSM) by including the charm quark according to the global U(4)r × U(4)l chiral symmetry. In the eLSM, besides scalar and pseudoscalar mesons, also vector and axial-vector mesons are present. Almost all the parameters of the model were fixed in a previous study of mesons below 2 GeV. In the extension to the four-flavor case, only three additional parameters (all of them related to the bare mass of the charm quark) appear.We compute the (OZI dominant) strong decays of open charmed mesons. The results are compatible with the experimental data, although the theoretical uncertainties are still large.
The electric dipole strength distribution in 130Te has been investigated using the method of Nuclear Resonance Fluorescence. The experiments were performed at the Darmstadt High Intensity Photon Setup using bremsstrahlung as photon source and at the High Intensity -Ray Source, where quasi-monochromatic and polarized photon beams are provided. Average decay properties of 130Te below the neutron separation energy are determined. Comparing the experimental data to the predictions of the statistical model indicate, that nuclear structure effects play an important role even at sufficiently high excitation energies. Preliminary results will be presented.
Death and the King's Grey Hair and Other Plays is a collection of three plays, 'Death and the King's Grey Hair, ' 'Truce with the Devil, ' and 'Fringe Benefits, ' which are all experimental plays from the early period of the writing career of Denja Abdullahi, who is presently renowned as a poet of populist expressions. 'Death and the King's Grey Hair' examines the use and misuse of absolute power based on an ancient Jukun myth of young kings and short reigns. 'Truce with the Devil' is a satire on the later abandonment of the creed of Marxism by its adherents, a kind of mockery of turncoat revolutionaries in the grip of practical social realities. 'Fringe Benefits', a radio play, is an expose of the happening in Nigeria's ivory towers, seen from the eyes of a participant-observer.
Has economic research been helpful in dealing with the financial crises of the early 2000s? On the whole, the answer is negative, although there are bright spots. Economists have largely failed to predict both crises, largely because most of them were not analytically equipped to understand them, in spite of their recurrence in the last 25 years. In the pre-crisis period, however, there have been important exceptions – theoretical and empirical strands of research that largely laid out the basis for our current thinking about financial crises. Since 2008, a flurry of new studies offered several different interpretations of the US crisis: to some extent, they point to potentially complementary factors, but disagree on their relative importance, and therefore on policy recommendations. Research on the euro debt crisis has so far been much more limited: even Europe-based researchers – including CEPR ones – have often directed their attention more to the US crisis than to that occurring on their doorstep. In terms of impact on policy and regulatory reform, the record is uneven. On the one hand, the swift and massive liquidity provision by central banks in the wake of both crises is, at least partly, to be credited to previous research on the role of central banks as lenders of last resort in crises and on the real effects of bank lending and monetary policy. On the other hand, economists have had limited impact on the reform of prudential and security market regulation. In part, this is due to their neglect of important regulatory choices, which policy-makers are therefore left to take without the guidance of academic research-based analysis.
Day and Night in Limbo
(2014)
With humour, insight and irony, Lonkog recounts the joys and contradictions of daily life in a Northern Cameroon village. Living in Carrefour Poli in Northern Cameroon was never easy. How far will one have to go for drinking water during the dry season? Will there be money for kerosene to fill the lamp tank? For batteries for the torch? For a bowl of corn to make 'fufu' for the family? Will there be a night encounter with the poison of a snake or scorpion? The man of Carrefour Poli imagines when he last had a bottle of beer and when he will next have another. Children sit in class staring at the teacher, while their work suffers. People sit under trees for shade only to cut them down for firewood. Ministers run up and down, working very hard and sweating, but little changes. Day and night people turn around on the same spot. It takes a long time to build a nation. Everything is in limbo.
Data structures and advanced models of computation on big data : report from Dagstuhl seminar 14091
(2014)
This report documents the program and the outcomes of Dagstuhl Seminar 14091 "Data Structures and Advanced Models of Computation on Big Data". In today's computing environment vast amounts of data are processed, exchanged and analyzed. The manner in which information is stored profoundly influences the efficiency of these operations over the data. In spite of the maturity of the field many data structuring problems are still open, while new ones arise due to technological advances.
The seminar covered both recent advances in the "classical" data structuring topics as well as new models of computation adapted to modern architectures, scientific studies that reveal the need for such models, applications where large data sets play a central role, modern computing platforms for very large data, and new data structures for large data in modern architectures.
The extended abstracts included in this report contain both recent state of the art advances and lay the foundation for new directions within data structures research.
Cytokine-regulated GADD45G induces differentiation and lineage selection in hematopoietic stem cells
(2014)
The balance of self-renewal and differentiation in long-term repopulating hematopoietic stem cells (LT-HSC) must be strictly controlled to maintain blood homeostasis and to prevent leukemogenesis. Hematopoietic cytokines can induce differentiation in LT-HSCs; however, the molecular mechanism orchestrating this delicate balance requires further elucidation. We identified the tumor suppressor GADD45G as an instructor of LT-HSC differentiation under the control of differentiation-promoting cytokine receptor signaling. GADD45G immediately induces and accelerates differentiation in LT-HSCs and overrides the self-renewal program by specifically activating MAP3K4-mediated MAPK p38. Conversely, the absence of GADD45G enhances the self-renewal potential of LT-HSCs. Videomicroscopy-based tracking of single LT-HSCs revealed that, once GADD45G is expressed, the development of LT-HSCs into lineage-committed progeny occurred within 36 hr and uncovered a selective lineage choice with a severe reduction in megakaryocytic-erythroid cells. Here, we report an unrecognized role of GADD45G as a central molecular linker of extrinsic cytokine differentiation and lineage choice control in hematopoiesis.
Over the past decade, Scandinavian and German scholars have been active in the redefinition of the terms “Vitalism” and “Vitalist” as descriptive categories for analytical purposes in the fields of literary and cultural history. In this context,“Vitalism”has primarily been used to describe an enthusiastic worshipping of life, one that holds youth, health, strength and beauty as its primary attributes, which was prevalent in all aspects of cultural life around 1900. But even the post war founders of the Vitalist re-conceptualisation of this era, Wolfdietrich Rasch and Gunter Martens, warned of taking such a unilateral view ofwhat constituted a Vitalist concept of life. It could lead to a misunderstanding of Vitalist way of thinking, Rasch said, if the focus wasonly set upon the enthusiastic surplus, the worshipping of youth and health. To Vitalists, life is more than that. It is a totality that also encompasses notions of destruction, decay and death. “All life symbols in literature around 1900 are at the same time symbols of death” (Rasch, 1967:24).Through the analyses of three poems, this article aims to show concrete examples of how cyclic Vitalist thinking is embedded in poetry of the era. The analyses include a further sub-categorisation to capture the different types of Life Force dealt with in the texts. By way of an introduction, Vitalism is discussed within the context of the scientific and social developments of the 19th Century.
Customer equity reporting
(2014)
WHARTON SCHOOL OF BUSINESS AT UNIVERSITY OF PHILADELPHIA HAS JUSTLAUNCHED AN 8-WEEK ONLINE PROGRAM “STRATEGIC VALUE OF CUSTOMER RELATIONSHIPS – ONLINE” TAUGHT BY MARKETING PROFESSOR AND AUTHOR PETER FADER. HE INVITED PROFESSOR SKIERA, DIRECTOR OF THE E-FINANCE LAB, TO PHILADELPHIA TO LEARN ABOUT HIS THOUGHTS ON “CUSTOMER EQUITY REPORTING”. THIS ARTICLE SUMMARIZES SOME OF PROFESSOR FADER’S QUESTIONS AND PROFESSOR SKIERA’S REPLIES.
Customary Law Ascertained Volume 2 is the second of a three volume series in which traditional authorities in Namibia present the customary laws of their communities. It contains the laws of the Bakgalagari, the Batswana ba Namibia and the Damara communities. The recognised traditional authorities in Namibia are expected to ascertain the customary law applicable in their respective communities and to note the most important aspects of the laws in written form. The Ministry of Regional and Local Government, Housing and Rural Development, and the Council of Traditional Leaders therefore initiated the ascertainment of customary law. The ascertainment project is housed in the Human Rights and Documentation Centre of the University of Namibia. The former Dean of the Faculty of Law of the University of Namibia, Professor Manfred O. Hinz, has directed the project since its inception.
One of the motivations for establishing a European banking union was the desire to break the ties with between national regulators and domestic financial institutions in order to prevent regulatory capture. However, supervisory authority over the financial sector at the national level can also have valuable public benefits. The aim of this policy letter is to detail these public benefits in order to counter discussions that focus only on conflicts of interest. It is informed by an analysis of how financial institutions interacted with policy-makers in the design of national bank rescue schemes in response to the banking crisis of 2008. Using this information, it discusses the possible benefits of close cooperation between financial institutions and regulators and analyzes these in the wake of a European banking union.
This collection of essays on archaeology and heritage studies is authored by local and expatriate scholars who are either past or current practitioners in archaeological work in Ghana. They are from Ghana, UK, US and Canada. The subject matter covered includes the history and evolution of the discipline in Ghana; the method and theory or 'how to do it' in archaeology, field research reports, and syntheses on findings from past and recent investigations. The eclectic or multidisciplinary strategy has been the research vogue in Ghanaian archaeology recently, and this is reflected in the various chapters. The essays engage with current theoretical trends in global archaeology and also focus on the role and status of archaeology as a discipline in Ghanaian society today. Archaeology is a relatively 'novel' subject to many in Ghana. This Reader will, therefore, be a huge asset to local students and experts alike. Foreign scholars will also find it very useful.
Neoadjuvant systemic chemotherapy is a possible therapeutic approach for the treatment of locally advanced operable, primarily non-operable or inflammatory breast cancer. Neoadjuvant systemic chemotherapy is an option for breast cancer patients who would require adjuvant chemotherapy otherwise based on clinical and histological examination and imaging. The use of neoadjuvant systemic therapy in operable breast cancer is currently increasing because of its advantages that include higher rates of breast conserving surgery and the possibility of measuring early in-vivo response to systemic treatment. The timing of axillary sentinel lymph node diagnosis (i.e. before or after neoadjuvant chemotherapy) is critical in that it may influence the likelihood of axillary preservation. It is not yet clear if neoadjuvant therapy might improve outcomes in certain subgroups of breast cancer patients. Neoadjuvant treatment modalities require a close collaboration between oncology professionals, including surgeons, gynecologists, medical oncologists, radiation oncologists, radiologists and pathologists. The most important parameter for treatment success and improved overall survival is the achievement of a pathologic complete response (pCR), although the role of pCR in patients with luminal A like tumours might be less informative. Identification of patient subgroups with high pCR rates may allow less invasive surgical or radiological interventions. Patients not achieving a pCR may be candidates for postoperative clinical trials exploring novel systemic treatments.
Introduction: Curare is one of the best-examined neurotoxins of the world, which has empirically been used for centuries by American Indigenes. Research on curare has been performed much later, a global scientometric analysis on curare research or its derivates does not yet exist. This bibliometric analysis is part of the global NewQis-project and should illuminate both toxic and historic issues of research on curare.
Methods: The ISI Web of Science was searched for data covering 1900 to 2013 using a term which included as many original articles on curare as possible. 3,867 articles were found and analyzed for common bibliometric items such as the number of citations, language of the articles or the (modified) Hirsch-Index (h-index). Results are illustrated utilizing modern density equalizing map projections (DEMP) or beam diagrams.
Results: Most publications were located in North America and Europe. The USA has the highest number of publications as well as the highest h-index. The number of publications overall rose until the late 1990s and later decreased. Furthermore, sudden increases of research activity are ascribable to historic events, like the first use of curare as muscle relaxant during surgery.
Discussion: This scientometric analysis of curare research reflects several tendencies as previously seen in other bibliometric investigations, i.e. the scientific quality standard of North America and Europe. Research on curare decreased however, due to the declining attention towards this muscle relaxant. This work exemplifies also how scientometric methods can be used to illuminate historic circumstances immediately stimulating scientific research.
Cultural heritage reconstructed - Compact Memory and the Frankfurt Digital Judaica Collection
(2014)
Compact Memory, the internet archive of German Jewish periodicals, provides free global internet access to the vast majority of German-Jewish newspapers and periodicals of the 19th and 20th century.
Jewish historical newspapers are the invaluable sources that supply direct and detailed information of the transformation process of Jewry and offer new insights into European Jewish history. The use of these historical sources however is extremely difficult, as complete sets of periodicals are very rarely to be found and they are scattered all over the world in different libraries and archives and in different physical formats (paper, microfilm).
Compact Memory contains the 110 most important Jewish German newspapers and periodicals in Central Europe in the period from 1806-1938, covering the complete range of religious, political, social, cultural and academic aspects of Jewish life. The texts are available partly as full-texts, processed by OCR, partly as graphic documents with corresponding index options. The database offers advanced search options, downloading and printing of articles. Thousands of essays of more than 10.000 individual contributors have been bibliographically indexed.
Compact Memory was established by the Judaica Division of the University Library Frankfurt am Main and in charge today in cooperation with the Aachen Chair of German-Jewish Literary History and the Cologne library Germania Judaica.
Compact Memory is one database within the Digital Collection Judaica which being part of Europeana and other digital portals offers resources for the reconstruction and representation of Jewish cultural heritage.
The title solvated salt, C29H41N2+·Br-·2CH2Cl2 was obtained from the reaction of the Arduengo-type carbene 1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-4,5-dimethyl-2H-imidazol-2-ylidene with Si2Br6 in dichloromethane. The complete cation is generated by a crystallographic mirror plane and the dihedral angle between the five-membered ring and the benzene ring is 89.8 (6)°; the dihedral angle between the benzene rings is 40.7 (2)°. The anion also lies on the mirror plane and both dichloromethane molecules are disordered across the mirror plane over two equally occupied orientations. In the crystal, the cations are linked to the anions via C-H...Br hydrogen bonds.
Colors and odors are associated; for instance, people typically match the smell of strawberries to the color pink or red. These associations are forms of crossmodal correspondences. Recently, there has been discussion about the extent to which these correspondences arise for structural reasons (i.e., an inherent mapping between color and odor), statistical reasons (i.e., covariance in experience), and/or semantically-mediated reasons (i.e., stemming from language). The present study probed this question by testing color-odor correspondences in 6 different cultural groups (Dutch, Netherlands-residing-Chinese, German, Malay, Malaysian-Chinese, and US residents), using the same set of 14 odors and asking participants to make congruent and incongruent color choices for each odor. We found consistent patterns in color choices for each odor within each culture, showing that participants were making non-random color-odor matches. We used representational dissimilarity analysis to probe for variations in the patterns of color-odor associations across cultures; we found that US and German participants had the most similar patterns of associations, followed by German and Malay participants. The largest group differences were between Malay and Netherlands-resident Chinese participants and between Dutch and Malaysian-Chinese participants. We conclude that culture plays a role in color-odor crossmodal associations, which likely arise, at least in part, through experience.
Molecular tumour targeting has significantly improved anti-cancer protocols. Still, the addition of molecular targeting to the treatment regime has not led to a curative breakthrough. Combined mammalian target of Rapamycin (mTOR) and histone deacetylase (HDAC) inhibition has been shown not only to enhance anti-tumour potential, but also to prevent resistance development seen under mono-drug therapy. This investigation was designed to evaluate whether cross-communication exists between mTOR signalling and epigenetic events regulated by HDAC. DU-145 prostate cancer cells were treated with insulin-like growth factor (IGF) to activate the Akt-mTOR cascade or with the HDAC-inhibitor valproic acid (VPA) to induce histone H3 and H4 acetylation (aH3, aH4). Subsequently, mTOR, Rictor, Raptor, p70s6k, Akt (all: total and phosphorylated), H3 and H4 (total and acetylated) were analysed by western blotting. Both techniques revealed a link between mTOR and the epigenetic machinery. IGF activated mTOR, Rictor, Raptor, p70s6k and Akt, but also enhanced aH3 and aH4. Inversely, IGFr blockade and knock-down blocked the Akt-mTOR axis, but simultaneously diminished aH3 and aH4. VPA treatment up-regulated histone acetylation, but also activated mTOR-Akt signalling. HDAC1 and 2 knock-down revealed that the interaction with the mTOR system is initiated by histone H3 acetylation. HDAC-mTOR communication, therefore, is apparent whereby tumour-promoting (Akt/mTORhigh, aH3/aH4low) and tumour-suppressing signals (Akt/mTORlow, aH3/aH4high) are activated in parallel. Combined use of an HDAC- and mTOR inhibitor might then diminish pro-tumour effects triggered by the HDAC- (Akt/mTORhigh) or mTOR inhibitor (aH3/aH4low) alone.
I analyze a critical illness insurance in a consumption-investment model over the life cycle. I solve a model with stochastic mortality risk and health shock risk numerically. These shocks are interpreted as critical illness and can negatively affect the expected remaining lifetime, the health expenses, and the income. In order to hedge the health expense effect of a shock, the agent has the possibility to contract a critical illness insurance. My results highlight that the critical illness insurance is strongly desired by the agents. With an insurance profit of 20%, nearly all agents contract the insurance in the working stage of the life cycle and more than 50% of the agents contract the insurance during retirement. With an insurance profit of 200%, still nearly all working agents contract the insurance, whereas there is little demand in the retirement stage.
This study presents a comprehensive and critical assessment of the meteorological conditions and atmospheric flow during the Lagrangian-type "Hill Cap Cloud Thuringia 2010" experiment (HCCT-2010). HCCT-2010 was performed in September and October 2010 at Mt. Schmücke in the Thuringian forest, Germany, applying three measurements sites (upwind, in-cloud, downwind) to study physical and chemical aerosol-cloud-interactions. A Lagrangian-type hill cap cloud experiment requires suitable cloud and particularly connected airflow conditions, i.e. representative air masses at the different measurement sites. Therefore, the present study aimed at the identification of time periods during the 6-weeks duration of the campaign, where such conditions were fulfilled and which can be used in further data examinations.
The following topics were studied in detail: (i) the general synoptic weather situations including the mesoscale flow conditions by means of a classification of advected air masses and calculation of non-dimensional flow parameters (e.g. Froude number), (ii) local meteorological conditions, including synoptic front passages, the presence of orographic or frontal cloudiness, cloud base heights and vertical stratification, and (iii) local flow conditions by means of statistical analyses using the quasi-inert trace gas ozone and selected size bins of particle number size distributions as well as SF6 tracer experiments in the campaign area. A comprehensive analyses using statistical measures such as the COD (Coefficient Of Divergence) and cross-correlation have been carried out for the first time in the context of a Lagrangian-type hill cap cloud experiment. Suitable criteria for the aimed statistical analyses were thus developed and applied in the present study to characterise the local flow connectivity in detail.
The comprehensive examination resulted in a total of 14 so-called "Full Cloud Events" (FCE), which are shown to conform to the Lagrange-type experimental philosophy of HCCT-2010. In addition, 15 so-called "Non-Cloud Events" (NCEs) could be established, which can be used as reference cases as they provide similarly suitable flow conditions but no cloud at the summit site. Orographic cloudiness was identified for approx. one third of the FCE periods, while about two thirds were associated to synoptic fronts. The statistical flow analyses indicate the existence of a strong link between the sites during the events, particularly under constant south-westerly flow conditions, high wind speeds and slightly stable stratification. The COD analyses using continuously measured concentrations of ozone and the 49 nm diameter particle bin revealed particularly for COD values below 0.1 very consistent time series, i.e. closely linked air masses between the different sites. The cross-correlation analysis revealed under connected flow conditions typical overflow times of about 15 to 30 min between the two valley sites. Additionally, the performed SF6 tracer experiments during the campaign clearly demonstrate that under appropriate meteorological conditions a Lagrangian-type approach is valid and that the connected flow validation procedure developed in this work is suitable for identifying such conditions. Finally, an overall evaluation of the identified FCEs is presented, which provides the basis for subsequent investigations of the measured chemical and physical data during HCCT-2010.
Expressivist theories of punishment, according to which a penal sanction articulates or expresses a certain meaning to the offender, to the victim and to society, become more and more prominent among the traditional theories of punishment as retribution or deterrence. What these theories have in common is the idea that the conveyance of the meaning is in need of a communicative action, and that the penal sanction is such a communicative act. This article argues that pure communicative theories of punishment face great difficulties in generating any justification for hard treatment. One challenge is that certain types of sanctions – in particularly, hard treatment – restrict the communicative opportunities of the incarcerated individual; which generates a paradox, in that it turns punishment into a communicative action of non-communication. Beyond that, moreover, all practices of hard treatment potentially become unnecessary, if expressing the moral message of censure constitutes a kind of action in itself, and as such, itself a treatment of the offender, embedded in a communicative relationship between offender, victim and society; such that we may be able to think of the history of punishment as a development where hard treatment becomes more and more unnecessary for the conveyance of the message.
The recent financial crisis highlighted the limits of the "originate to distribute" model of banking, but its nexus with the macroeconomy remains unexplored. I build a business cycle model with banks engaging in credit risk transfer (CRT) under informational externalities. Markets for CRT provide liquidity insurance to banks, but the emergence of a pooling equilibrium can also impair the banks’ monitoring incentives. In normal times and in face of standard macro shocks the insurance benefits of CRT prevail and the business cycle is stabilized. In face of financial/liquidity shocks the extent of informational asymmetries is larger and the business cycle is amplified. The macro model with CRT can also reproduce well a number of macro and banking statistics over the period of rapid growth of this banks’ business model.
We examine the effects of credit default swaps (CDS), a major type of over-the-counter derivative, on the corporate liquidity management of the reference firms. CDS help firms to access the credit market since the lenders can hedge their credit risk more easily using these contracts. However, CDS-protected creditors can be tougher in debt renegotiations and less willing to support distressed borrowers, causing some firms to become more cautious. Consequently, we find that firms hold significantly more cash after the inception of CDS trading on their debt. The increase in cash holdings by CDS firms is more pronounced for financially constrained firms and firms facing higher refinancing risk. Moreover, bank relationships and outstanding credit facilities intensify the CDS effect on cash holding. Finally, firms with greater financial expertise hold more cash when their debt is referenced by CDS. These findings suggest that CDS, which are primarily a risk management tool for lenders, induce firms to adopt more conservative liquidity policies.
Seven years after the launch of the European Paediatric Medicine Regulation, limited progress in paediatric oncology drug development remains a major concern amongst stakeholders – academics, industry, regulatory authorities, parents, patients and caregivers. Restricted increases in early phase paediatric oncology trials, legal requirements and regulatory pressure to propose early Paediatric Investigation Plans (PIPs), missed opportunities to explore new drugs potentially relevant for paediatric malignancies, lack of innovative trial designs and no new incentives to develop drugs against specific paediatric targets are some unmet needs. Better access to new anti-cancer drugs for paediatric clinical studies and improved collaboration between stakeholders are essential. The Cancer Drug Development Forum (CDDF), previously Biotherapy Development Association (BDA), with Innovative Therapy for Children with Cancer Consortium (ITCC), European Society for Paediatric Oncology (SIOPE) and European Network for Cancer Research in Children and Adolescents (ENCCA) has created a unique Paediatric Oncology Platform, involving multiple stakeholders and the European Union (EU) Commission, with an urgent remit to improve paediatric oncology drug development. The Paediatric Oncology Platform proposes to recommend immediate changes in the implementation of the Regulation and set the framework for its 2017 revision; initiatives to incentivise drug development against specific paediatric oncology targets, and repositioning of drugs not developed in adults. Underpinning these changes is a strategy for mechanism of action and biology driven selection and prioritisation of potential paediatric indications rather than the current process based on adult cancer indications. Pre-competitive research and drug prioritisation, early portfolio evaluation, cross-industry cooperation and multi-compound/sponsor trials are being explored, from which guidance for innovative trial designs will be provided.
Jirds (genus Meriones) are a diverse group of rodents, with a wide distribution range in Iran. Sundevall’s jird (Meriones crassus Sundevall, 1842) is one such species that shows a disjunct distribution, found on the Iranian Plateau and Western Zagros Mountains. Morphological differences observed between these two populations, however, lack quantitative support. Morphological differences between geographical populations of Meriones crassus were analysed and compared with those of the sympatric M. libycus. Similarities in the cranial morphology of these species were found, e.g. in a relatively large and inflated bulla. A two-dimensional geometric morphometric analysis was done on the skull of 275 M. crassus and 220 M. libycus from more than 70 different localities in their distribution range. Results confirm cranial differences between specimens of M. crassus from the Western Zagros and those from Africa and Arabia, mainly at the level of the relative size of the tympanic bulla, that were significantly correlated with the annual rainfall and elevation. Moreover, the study supports the hypothesis that the Western Zagros specimens are both a geographically and phenotypically distinct group compared to the other Iranian M. crassus specimens, suggesting that the former might be a distinct species.
Irene Heim in unpublished work proposed a new syntax-semantics interface for propositional attitude reports based on an ontology without transworld individuals, but counterpart functions instead. We show that the approach can capture the 'de re'/'de dicto' distinction, but makes different predictions from accounts with transworld individuals. Specifically, the account uses a non-invertible counterpart functions: a single individual in an alternative world can be the counterpart of many individuals of the real world. The directionality of counterpart functions predicts that a 'de dicto' interpreted DP cannot be an argument of a 'de re' interpreted predicate. We show that the predicted restriction is corroborated by existing work on restrictions on 'de re' interpretation. The derivation of constraints on 'de re' interpretation argues empirically for the counterpart ontology and Heim’s implementation thereof.
This volume charts the widening frontiers of black literary aesthetics using the prose and dramatic fictions of writers from Africa and the African diaspora. The chapters come in two interactive phases of current critical discourses involving rejoinders from past-present concerns and issues of cultural and contemporary modernity. These studies stress the argument that African literature is hardly discussed outside contemporary history and that the reason for the apparent disconnection among groups in Africa and the diaspora can be traced to the disparate elements within the continent and diaspora.
Coscinodon humilis was described by Milde from mica schist in the Passeiertal NE Merano (formerly southern Tyrolia in Austria, hence cited as Austria by Greven 1995. now Alto Adige in Italy). Limpricht (1890) regarded it as “verkümmerte Form von C. cribrosus”, and although Mönkemeyer (1927) still cited it, the species got forgotten by the time. Thus the species was no more mentioned by Corley et al (1981) in the European checklist and therefore no more included by Frey et al. (1995) in the German edition of the “Moos- und Farnpflanzen Europas”. Greven (1995) re-established the species in his treatment of Grimmia (and related genera) in Europe. Therefore Frey et al. (2006) included the species, which was, however, not keyed out. Finally Hill et al. (2006) listed it again in the new European checklist as a good species.
Correlative microscopy incorporates the specificity of fluorescent protein labeling into high-resolution electron micrographs. Several approaches exist for correlative microscopy, most of which have used the green fluorescent protein (GFP) as the label for light microscopy. Here we use chemical tagging and synthetic fluorophores instead, in order to achieve protein-specific labeling, and to perform multicolor imaging. We show that synthetic fluorophores preserve their post-embedding fluorescence in the presence of uranyl acetate. Post-embedding fluorescence is of such quality that the specimen can be prepared with identical protocols for scanning electron microscopy (SEM) and transmission electron microscopy (TEM); this is particularly valuable when singular or otherwise difficult samples are examined. We show that synthetic fluorophores give bright, well-resolved signals in super-resolution light microscopy, enabling us to superimpose light microscopic images with a precision of up to 25 nm in the x-y plane on electron micrographs. To exemplify the preservation quality of our new method we visualize the molecular arrangement of cadherins in adherens junctions of mouse epithelial cells.
Multiple sources of confusion surround the identity of Ochodaeus grandiceps Fairmaire, 1897, from Sichuan, China (Coleoptera: Ochodaeidae). Herein the type specimen is illustrated to solve these taxonomic issues. Examination of the holotype indicates that the species must be transferred to the genus Nothochodaeus Nikolajev, 2005, resulting in a new combination. The genus Mimochodaeus Nikolajev, 2009, based on a misidentifi cation of O. grandiceps as its purported type species, is discussed. Finally, Cuban specimens had been treated erroneously as belonging to O. grandiceps, and so the species had remained undescribed. A new species, Parochodaeus perdidus, is described to accommodate them.
This paper contrasts the recent European initiatives on regulating corporate groups with alternative approaches to the phenomenon. In doing so it pays particular regard to the German codified law on corporate groups as the polar opposite to the piecemeal approach favored by E.U. legislation.
It finds that the European Commission’s proposal to submit (significant) related party transactions to enhanced transparency, outside fairness review, and ex ante shareholder approval is both flawed in its design and based on contestable assumptions on informed voting of institutional investors. In particular, the contemplated exemption for transactions with wholly owned subsidiaries allows controlling shareholders to circumvent the rule extensively. Moreover, vesting voting rights with (institutional) investors will not lead to the informed assessment that is hoped for, because these investors will rationally abstain from active monitoring and rely on proxy advisory firms instead whose competency to analyze non-routine significant related party transactions is questionable.
The paper further delineates that the proposed recognition of an overriding interest of the group requires strong counterbalances to adequately protect minority shareholders and creditors. Hence, if the Commission choses to go down this route it might end up with a comprehensive regulation that is akin to the unpopular Ninth Company Law Directive in spirit, though not in content. The latter prediction is corroborated by the pertinent parts of the proposal for a European Model Company Act.
It has become increasingly apparent over the last decades that cooking pottery played a considerable role as a trade commodity in ancient times, yet relatively little research has yet been done on this topic for its own sake. By taking a closer look at the cooking pottery found in Priene, a small city in southern Ionia re-founded in the middle of the 4th century BCE, we want to trace some of the broader developments within the cooking wares that were used over a period of roughly 300 years. The aim is not only to outline the general shapes that were in use over this period of time, but also to register if and how these shapes correlate with the different fabrics observed in Priene so far.
Conviviality in Bellville: An Ethnography of Space, Place, Mobility and Being in Urban South Africa
(2014)
This book provides insight into the experiences of mobility and migration in contemporary South Africa, contributing to a field of literature about multiculturalism and urban public space in globalizing cities. It takes into consideration the greater international political and local socio-economic factors that drive migration, relationships and conviviality, and how they are intertwined in the everyday narrative of 'insiders' and 'outsiders'. The Bellville central business district demonstrates the realities of interconnected local and global hierarchies of citizenship and belonging and how they emerge in a world of accelerated mobility. The book further demonstrates how the emergence of conviviality in everyday public life represents a critical field for contemplating contemporary notions of human rights, citizenship and belonging.
Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
Myocardial infarction (MI) induces a complex inflammatory immune response, followed by the remodelling of the heart muscle and scar formation. The rapid regeneration of the blood vessel network system by the attraction of hematopoietic stem cells is beneficial for heart function. Despite the important role of chemokines in these processes, their use in clinical practice has so far been limited by their limited availability over a long time-span in vivo. Here, a method is presented to increase physiological availability of chemokines at the site of injury over a defined time-span and simultaneously control their release using biodegradable hydrogels. Two different biodegradable hydrogels were implemented, a fast degradable hydrogel (FDH) for delivering Met-CCL5 over 24 hrs and a slow degradable hydrogel (SDH) for a gradual release of protease-resistant CXCL12 (S4V) over 4 weeks. We demonstrate that the time-controlled release using Met-CCL5-FDH and CXCL12 (S4V)-SDH suppressed initial neutrophil infiltration, promoted neovascularization and reduced apoptosis in the infarcted myocardium. Thus, we were able to significantly preserve the cardiac function after MI. This study demonstrates that time-controlled, biopolymer-mediated delivery of chemokines represents a novel and feasible strategy to support the endogenous reparatory mechanisms after MI and may compliment cell-based therapies.
We examine the relationship between household wealth and self-control. Although self-control has been linked to consumption and financial behavior, its measurement remains an open issue. We employ a definition of self-control failure that follows literature in psychology, suggesting that three factors can render self-control defective: lack of planning, lack of monitoring, and lack of commitment to pre-set plans. Our measure combines those three ingredients and can be computed using a standard representative survey. We find that self-control failure is strongly associated with different household net wealth measures and with self-assessed financial distress.
Heterogenous subtypes of breast cancer need to be analyzed separately. Pooling of datasets can provide reasonable sample sizes but dataset bias is an important concern. We assembled a combined dataset of 579 Affymetrix microarrays from triple negative breast cancer (TNBC) in Gene Expression Omnibus (GEO) series GSE31519. We developed a method for selecting comparable datasets and to control for the amount of dataset bias of individual probesets.
Mechanics has an important role during morphogenesis, both in the generation of forces driving cell shape changes and in determining the effective material properties of cells and tissues. Drosophila dorsal closure has emerged as a reference model system for investigating the interplay between tissue mechanics and cellular activity. During dorsal closure, the amnioserosa generates one of the major forces that drive closure through the apical contraction of its constituent cells. We combined quantitation of live data, genetic and mechanical perturbation and cell biology, to investigate how mechanical properties and contraction rate emerge from cytoskeletal activity. We found that a decrease in Myosin phosphorylation induces a fluidization of amnioserosa cells which become more compliant. Conversely, an increase in Myosin phosphorylation and an increase in actin linear polymerization induce a solidification of cells. Contrary to expectation, these two perturbations have an opposite effect on the strain rate of cells during DC. While an increase in actin polymerization increases the contraction rate of amnioserosa cells, an increase in Myosin phosphorylation gives rise to cells that contract very slowly. The quantification of how the perturbation induced by laser ablation decays throughout the tissue revealed that the tissue in these two mutant backgrounds reacts very differently. We suggest that the differences in the strain rate of cells in situations where Myosin activity or actin polymerization is increased arise from changes in how the contractile forces are transmitted and coordinated across the tissue through ECadherin-mediated adhesion. Altogether, our results show that there is an optimal level of Myosin activity to generate efficient contraction and suggest that the architecture of the actin cytoskeleton and the dynamics of adhesion complexes are important parameters for the emergence of coordinated activity throughout the tissue.
9.01 This chapter outlines the development of Contingent Convertible Securities (CoCos) for financial institutions from their theoretical origins to their current form under the European Union’s Fourth Capital Requirements Directive framework and its Bank Recovery and Resolution Directive and examines the effect the framework and the directive have had on their design and ability to fulfill the ends for which they were initially conceived. It examines this from two viewpoints: the policy goals CoCos are meant to achieve and the corporate law issues raised by the requirements of CRD IV. On the policy side we conclude that CRD IV and the RRD have significantly limited the amount of CoCos a financial institution is likely to issue, but expanded their possible forms by including write-down as well as convertible structures and narrowed the differences between them and pure regulatory bail-in structures, thus calling into question whether they are truly ‘going concern’ rather than ‘gone concern’ capital. On the company law side we conclude that a number of issues, in particular the limits on an authorization of management to issue CoCos and shares, the scope of the shareholders’ right of pre-emption, the concept of dilution and the distinction between contributions in cash and in kind merit closer attention than they appear to have received in the current discussion on CoCos.
Der diesjährige 9. Trockenrasen-Sonderteil von Tuexenia beginnt mit einem Bericht über die aktuellen Aktivitäten der European Dry Grassland Group (EDGG). Zunächst geben wir einen Überblick über die Entwicklung der Mitgliederzahl. Dann berichten wir vom letzten European Dry Grassland Meeting in Zamość (Polen, 2013) und vom letzten European Dry Grassland Field Workshop in Chakassien (Russland, 2013) und informieren über künftige Veranstaltungen der EDGG. Anschließend erläutern wir die Publikationsaktivitäten der EDGG. Im zweiten Teil des Editorials geben wir eine Einführung zu den fünf Artikeln des diesjährigen Trockenrasen-Sonderteils: Zwei davon beschäftigen sich mit der Syntaxonomie von Trockenrasen in Osteuropa: Der eine Artikel präsentiert erstmalig eine nach internationalen Nomenklaturregeln gültige Liste der Trockenrasengesellschaften Serbiens während der andere die Ergebnisse des zweiten EDGG-Field Workshop 2010 nach Podolien (Ukraine) vorstellt. Im dritten Artikel werden kryophytische Steppen in Südsibirien (Russland) analysiert. Der vierte Artikel analysiert in Böhmen (Tschechien) die bestimmenden Kräfte für Artenreichtum und Artenzusammensetzung der Trockenrasen. Der fünfte Artikel befasst sich mit der Auswahl von Wiederansiedlungsarten am Beispiel der Steppenrasen in Thüringen (Deutschland).
The pi-calculus is a well-analyzed model for mobile processes and mobile computations.
While a lot of other process and lambda calculi that are core languages of higher-order concurrent and/or functional programming languages use a contextual semantics observing the termination behavior of programs in all program contexts, traditional program equivalences in the pi-calculus are bisimulations and barbed testing equivalences, which observe the communication capabilities of processes under reduction and in contexts.
There is a distance between these two approaches to program equivalence which makes it hard to compare the pi-calculus with other languages. In this paper we contribute to bridging this gap by investigating a contextual semantics of the synchronous pi-calculus with replication and without sums.
To transfer contextual equivalence to the pi-calculus we add a process Stop as constant which indicates success and is used as the base to define and analyze the contextual equivalence which observes may- and should-convergence of processes.
We show as a main result that contextual equivalence in the pi-calculus with Stop conservatively extends barbed testing equivalence in the (Stop-free) pi-calculus. This implies that results on contextual equivalence can be directly transferred to the (Stop-free) pi-calculus with barbed testing equivalence.
We analyze the contextual ordering, prove some nontrivial process equivalences, and provide proof tools for showing contextual equivalences. Among them are a context lemma, and new notions of sound applicative similarities for may- and should-convergence.
I numerically solve realistically calibrated life cycle consumption-investment problems in continuous time featuring stochastic mortality risk driven by jumps, unspanned labor income as well as short-sale and liquidity constraints and a simple insurance. I compare models with deterministic and stochastic hazard rate of death to a model without mortality risk. Mortality risk has only minor effects on the optimal controls early in the life cycle but it becomes crucial in later years. A diffusive component in the hazard rate of death has no significant impact, whereas a jump component is desired by the agent and influences optimal controls and wealth evolution. The insurance is used to ensure optimal bequest such that there is no accidental bequest. In the absence of the insurance, the biggest part of bequest is accidental.
Consumption-based asset pricing with rare disaster risk : a simulated method of moments approach
(2014)
The rare disaster hypothesis suggests that the extraordinarily high postwar U.S. equity premium resulted because investors ex ante demanded compensation for unlikely but calamitous risks that they happened not to incur. Although convincing in theory, empirical tests of the rare disaster explanation are scarce. We estimate a disaster-including consumption-based asset pricing model (CBM) using a combination of the simulated method of moments and bootstrapping. We consider several methodological alternatives that differ in the moment matches and the way to account for disasters in the simulated consumption growth and return series. Whichever specification is used, the estimated preference parameters are of an economically plausible size, and the estimation precision is much higher than in previous studies that use the canonical CBM. Our results thus provide empirical support for the rare disaster hypothesis, and help reconcile the nexus between real economy and financial markets implied by the consumption-based asset pricing paradigm.
he observed hump-shaped life-cycle pattern in individuals' consumption cannot be explained by the classical consumption-savings model. We explicitly solve a model with utility of both consumption and leisure and with educational decisions affecting future wages. We show optimal consumption is hump shaped and determine the peak age. The hump results from consumption and leisure being substitutes and from the implicit price of leisure being decreasing over time; more leisure means less education, which lowers future wages, and the present value of foregone wages decreases with age. Consumption is hump shaped whether the wage is hump shaped or increasing over life.