Bringing the past to heel: History, identity and violence in Ian McEwan's Black Dogs

Ian McEwan's 1992 novel Black Dogs employs postmodern understandings of history while also critiquing these same perspectives. In particular, by depicting the efforts of its protagonist, Jeremy, to write a memoir of his parents-in-law, it draws attention to the subjectivity of historical writing. While this quality has led some critics to condemn the novel for its escapism and amorality, the authors of the essay argue that Black Dogs is a statement about the necessity of history rather than its futility. Indeed, they read the text as a dramatization of humanity-s ability to bear rather than escape the often troubling burden of the past and an endorsement of the writing of history despite the awareness that historiography, while serving deep-seated human needs, is always problematic

Multiple outcomes for PI3K/Akt/mTOR targeting in non-Hodgkin lymphoma

Wachstumsfaktor bedingte Aktivierung des PI3K/Akt/mTOR Signalweg wirkt positiv auf Vermehrung und Überleben. Konstitutive Aktivierung des Signalweges in NHL ist jedoch an Tumorprogression und Therapieresistenz beteiligt. Am Zelllinienmodell wurden zwei mögliche Therapiestrategien der PI3K/Akt/mTOR Inhibition erprobt, PI3K Inhibition mit BKM120 und horizontale Kombination von Zytostatika mit PI3K/Akt/mTOR Inhibitoren Erstens, BKM120 hat Antitumoraktivität in NHL und induziert Zelltod. Auf molekularer Ebene führt BKM120 vermittelte Dephosphorylierung von CDK1 an Y15 zur Aktivierung des M-Phase Komplex CDK1/Zyklin B und Eintritt in die Mitose. Parallel erlaubt die Degradation von Zyklin A und Hochregulation von Zyklin B Progression bis zur Metaphase, hemmt jedoch die Transition in die Anaphase. Anhaltender Metaphasearrest bewirkt programmierten Zelltod über den intrinsischen Signalweg der Apoptose durch Hochregulation der BH3-onlys Puma und Hrk, Aktivierung von Bax/Bak und proteolytische Spaltung von Caspase 9. Verlust von Bax/Bak oder Caspase Inhibition schützt vor BKM120 vermitteltem Zelltod. Bax/Bak defiziente Zellen, welche zusätzlich p53 Mutationen aufweisen, werden polyploid. Die Polyploidie ist ATM-MEK1/2 abhängig und kann mit Caffeine oder U0126blockiert werden. Zur Vermeidung von Polyploidie bedingter Tumorprogression, sollte BKM120 nur in Verbindung mit MAPK/ATM Inhibitoren verwendet werden. Zweitens. Horizontale Kombination PI3K/Akt/mTOR Inhibitoren mit cytotoxischen Substanzen schützt vor Apoptose. Der Schutzeffekt tritt auschließlich bei niedrigen Konzentration auf und ist unabhängig von der Art des Inhibitors bzw. Ebene der Inhibition. Das Onkogen und NFkB Target Pim-2 ist möglicherweise am Schutzmechanismus beteiligt. Durch die PI3K/Akt/mTOR vermittelte Pim-2 Regulation ergibt sich eine neue Rückkopplungsschleife. Im Fazit erschwert die Komplexizität des PI3K/Akt/mTOR Signalweges die Etablierung von Therapien.Growth factor mediated activation of the PI3K/Akt/mTOR pathway positively regulates proliferation and survival. Constitutive activation in NHL, however, is correlated with tumor progression and therapeutic resistance. Therefore, two possible strategies were tested in a cell line model system, Inhibition of PI3K with BKM120 and PI3K/Akt/mTOR Inhibition in addition to cytostatic drug administration. First, it is demonstrated that the pan PI3K inhibitor BKM120 has antitumor activity in NHL and induces cell death. On molecular level, BKM120 mediated dephosphorylation of CDK1 on Y15 causes activation of the M-phase complex CDK1/Cyclin B and entry into mitosis. In parallel, degradation of Cyclin A and Upregulation of Cyclin B enables progression into metaphase but inhibits transition into anaphase. Prolonged metaphase arrest induces programmed cell death via the intrinsic apoptosis pathway by upregulation of the BH3-onlys Puma and Hrk, activation of Bax/Bak and proteolytic cleavage of caspase-9. Loss of Bax/Bak or caspase inhibition protects from BKM120 induced apoptosis. Bax/Bak deficient cells with additional p53 mutation become polyploid. This polyploidy is ATM-MEK1/2 dependent and can be blocked with Caffeine or U0126. To prevent polyploidy related tumor progression, BKM120 should administered only in combination with ATM or MEK inhibitors. Second, combination of PI3K/Akt/mTOR inhibitors with cytotoxic agents protects from apoptosis. The protective effect is only detectable with low PI3K/Akt/mTOR inhibitor concentrations and independent of inhibitor type or cascade level. The oncogene and NFkB target is possibly involved in apoptosis protection and inhibition of NFkB neutralizes the protective effect. PI3K/Akt/mTOR mediated Pim-2 regulation reveals a new feedback loop within the pathway. In conclusion, the complexity of the PI3K/Akt/mTOR pathway impedes therapeutic targeting

Determination of the actual morphology of core-shell nanoparticles by advanced X-ray analytical techniques: A necessity for targeted and safe nanotechnology

Obwohl wir sie oft nicht bewusst wahrnehmen, sind Nanopartikel heutzutage in den meisten Bereichen unseres Alltags präsent, unter anderem in Lebensmitteln und ihren Verpackungen, Medizin, Medikamenten, Kosmetik, Pigmenten und in elektronischen Geräten wie Computermonitoren. Ein Großteil dieser Partikel weist, beabsichtigt oder unbeabsichtigt, eine Kern-Schale Morphologie auf. Einfachheitshalber wird diese Morphologie eines Kern-Schale-Nanopartikels (CSNP) oft als ideal angenommen, d.h. als ein sphärischer Kern, der komplett von einer Schale homogener Dicke bedeckt ist, mit einer scharfen Grenzfläche zwischen Kern- und Schalenmaterial. Außerdem wird vielfach auch davon ausgegangen, alle Partikel der Probe hätten gleiche Schalendicken. Tatsächlich weichen die meisten realen CSNPs in verschiedenster Weise von diesem Idealmodell ab, mit oft drastischen Auswirkungen darauf, wie gut sie ihre Aufgabe in einer bestimmten Anwendung erfüllen. Das Thema dieser kumulativen Doktorarbeit ist die exakte Charakterisierung der wirklichen Morphologie von CSNPs mit modernen Röntgen-basierten Methoden, konkret Röntgen-Photoelektronen-Spektroskopie (XPS) und Raster-Transmissions-Röntgen-Mikroskopie (STXM). Der Fokus liegt insbesondere auf CSNPs, die von einer idealen Kern-Schale-Morphologie abweichen. Aufgrund der enormen Vielfalt an CSNPs, die sich in Material, Zusammensetzung und Form unterscheiden, kann eine Messmethode nicht völlig unverändert von einer Probe auf eine andere übertragen werden. Nichtsdestotrotz, da die als Teil dieser Doktorarbeit präsentierten Artikel eine deutlich ausführlichere Beschreibung der Experimente enthalten als vergleichbare Publikationen, stellen sie eine wichtige Anleitung für andere Wissenschaftler dafür dar, wie aussagekräftige Informationen über CSNPs durch Oberflächenanalytik erhalten werden können.Even though we often do not knowingly recognize them, nanoparticles are present these days in most areas of our daily life, including food and its packaging, medicine, pharmaceuticals, cosmetics, pigments as well as electronic products, such as computer screens. The majority of these particles exhibits a core-shell morphology either intendedly or unintendedly. For the purpose of practicability, this core-shell nanoparticle (CSNP) morphology is often assumed to be ideal, namely a spherical core fully encapsulated by a shell of homogeneous thickness with a sharp interface between core and shell material. It is furthermore widely presumed that all nanoparticles in the sample possess the same shell thickness. As a matter of fact, most real CSNPs deviate in several ways from this ideal model with quite often severe impact on how efficiently they perform in a specific application. The topic of this cumulative PhD thesis is the accurate characterization of the actual morphology of CSNPs by advanced X-ray analytical techniques, namely X-ray photoelectron spectroscopy (XPS) and scanning transmission X-ray microscopy (STXM). A special focus is on CSNPs which deviate from an ideal core-shell morphology. Due to the vast diversity of nanoparticles differing in material, composition and shape, a measurement procedure cannot unalteredly be transferred from one sample to another. Nevertheless, because the articles in this thesis present a greater depth of reporting on the experiments than comparable publications, they constitute an important guidance for other scientists on how to obtain meaningful information about CSNPs from surface analysis

The recognition of the prosodic focus position in German-learning infants from 4 to 14 months

The aim of the present study was to elucidate in a study with 4-, 6-, 8-, and 14-month-old German-learning children, when and how they may acquire the regularities which underlie Focus-to-Stress Alignment (FSA) in the target language, that is, how prosody is associated with specific communicative functions. Our findings suggest, that 14-month-olds have already found out that German allows for variable focus positions, after having gone through a development which goes from a predominantly prosodically driven processing of the input to a processing where prosody interacts more and more with the growing lexical and syntactic knowledge of the child

Development of a panel dataset from the IAB Establishment Panel cross-sectional data

"The IAB Establishment Panel now consists of 12 waves from 1993-2004, which are available for research use in the Research Data Centre of the Federal Employment Agency at the Institute for Employment Research. Due to repeated surveys of the same establishments, individual processes within the establishments can be studied in both cross-sectional and longitudinal terms. Cross-sectional evaluations of various waves and the production of a longitudinal or panel dataset require different tasks to be solved. Researchers must check across the individual survey years whether the variable values have remained identical or whether values are absent or new ones have been added. In addition, the measurement levels of the variables must be checked and any differences must be harmonised. Further, the time period in question can alter (e.g. financial year or first half-year). The purpose of such checks is to guarantee the comparability of the variables beyond the analysis period. The above examples illustrate that producing a panel dataset involves time-consuming processing of the individual datasets. This report has been written as a tool to support users in producing a panel dataset on the basis of data from the IAB Establishment Panel. The Datenreport consists of the development of a panel dataset containing variables that tend to be frequently used, in our experience. The panel dataset is available in the Research Data Centre and can be used both via remote data access and during research visits. The STATA and SPSS program code used to produce the dataset is available as a download, enabling users to integrate additional variables into the program code used with relative ease. The program codes can also be modified with the aid of the test data. This Datenreport is structured as follows: following a brief description of the IAB Establishment Panel, the structure of the panel dataset is presented. Next, Chapter 4 presents the variables for the dataset in the form of tables and details the use of the program codes. Appendix 1 describes each of the variables in the panel dataset, also detailing the values and any restrictions or problems occurring. Appendix 2 presents frequency counts1 of the variables used. The program codes in SPSS and STATA are contained in a separate document." (Author's abstract, IAB-Doku) ((en)) Additional Information Supplementary volume of FDZ-Datenreport 02/2006, including wave 2005 Appendix 1: SPSS program code Appendix 2: STATA program code Here you can find the German version.IAB-Betriebspanel, Datenorganisation, angewandte Statistik, IAB, Forschungsdatenzentrum, Längsschnittuntersuchung, Querschnittuntersuchung, Panel

Urban Cycling and Automated Vehicles

Connected and automated vebicles (CA Vs) will shape traffic patterns in the future and greatly influence urban mobility. A particular challenge for CAVs is to anticipate the movements of other road users. This applies especially to micromobility vehicles (bicycles, smaU electric vehicles), whose traffic behaviour is difficult to predict and shaped from individual behaviour. The increasing coexistence of CAVs and other, conventionally driven modes of transport thus has a growing impact as well as multiple consequences for urban structures and public space. The following fundamental trends will shape the way people live together in cities in the coming years: 1. increasing share of CAVs and micromobility, 2. renaissance ofthe mixed and liveable city, 3. changes in mobility behaviour and the appreciation of public space ( especially due to climate change and the Covid 19-pandemic), as weil as 4. technical upgrading of infrastructure. These parallel developments will lead to both conflicts and opportunities for cities.[from Introduction

Radiological and laboratory prognostic parameters for gastric dilation in rabbits (Oryctolagus cuniculus)

Background The aim of this study was to evaluate the radiographical and laboratory findings in pet rabbits with gastric dilation (GD) and identify prognostic parameters. Methods One hundred and fifty-five rabbits with GD were included for the radiographical analyses and 75 for the laboratory analyses. A vertebral stomach score (VSS) was established to determine the extension of the stomach on lateral radiographs. In addition, the caudal limit of gastric distention and the extension and position of gas accumulation in the stomach were recorded. Results The VSS was significantly higher in rabbits with GD than in healthy rabbits (p = 0.001). Extensive amounts of gas accumulation in the stomach (p = 0.001) and a ventral or central location of gas accumulation (p = 0.023) were associated with significantly increased mortality. Azotemia (51%), hyperglycaemia (44%) and hyponatraemia (37%) were the most frequent biochemical alterations in rabbits with GD. Limitations Due to the retrospective nature of the data, the cause of GD could not be determined in all animals. Conclusion Rabbits with GD and severe alterations in glucose, creatinine and sodium concentrations, ventral or central gas accumulations and a large amount of gas in the stomach had a poor prognosis