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Self-narratives of patients have received increasing interest in schizophrenia since they offer unique material to study patients’ subjective experience related to their illness, in particular the alteration of self that accompanies schizophrenia. In this study, we investigated the life narratives and the ability to integrate and bind memories of personal events into a coherent narrative in 27 patients with schizophrenia and 26 controls. Four aspects of life narratives were analyzed: coherence with cultural concept of biography, temporal coherence, causal-motivational coherence and thematic coherence. Results showed that in patients cultural biographical knowledge is preserved, whereas temporal coherence is partially impaired. Furthermore, causal-motivational and thematic coherence are significantly impaired: patients have difficulties explaining how events have modeled their identity, and integrating different events along thematic lines. Impairment of global causal-motivational and thematic coherence was significantly correlated with patients’ executive dysfunction, suggesting that cognitive impairment observed in patients could affect their ability to construct a coherent narrative of their life by binding important events to their self. This study provides new understanding of the cognitive deficits underlying self-disorders in patients with schizophrenia. Our findings suggest the potential usefulness of developing new therapeutic interventions to improve autobiographical reasoning skills.
Emerging evidence indicates that protein synthesis and degradation are necessary for the remodeling of synapses. These two processes govern cellular protein turnover, are tightly regulated, and are modulated by neuronal activity in time and space. The anisotropic anatomy of the neurons presents a challenge for the study of protein turnover, but the understanding of protein turnover in neurons and its modulation in response to activity can help us to unravel the fine-tuned changes that occur at synapses in response to activity. Here we review the key experimental evidence demonstrating the role of protein synthesis and degradation in synaptic plasticity, as well as the turnover rates of specific neuronal proteins.
Microstructural abnormalities in white matter (WM) are often reported in Alzheimer’s disease (AD) and may reflect primary or secondary circuitry degeneration (i.e., due to cortical atrophy). The interpretation of diffusion tensor imaging (DTI) eigenvectors, known as multiple indices, may provide new insights into the main pathological models supporting primary or secondary patterns of WM disruption in AD, the retrogenesis, and Wallerian degeneration models, respectively. The aim of this review is to analyze the current literature on the contribution of DTI multiple indices to the understanding of AD neuropathology, taking the retrogenesis model as a reference for discussion. A systematic review using MEDLINE, EMBASE, and PUBMED was performed. Evidence suggests that AD evolves through distinct patterns of WM disruption, in which retrogenesis or, alternatively, the Wallerian degeneration may prevail. Distinct patterns of WM atrophy may be influenced by complex interactions which comprise disease status and progression, fiber localization, concurrent risk factors (i.e., vascular disease, gender), and cognitive reserve. The use of DTI multiple indices in addition to other standard multimodal methods in dementia research may help to determine the contribution of retrogenesis hypothesis to the understanding of neuropathological hallmarks that lead to AD.
Microstructural abnormalities in white matter (WM) are often reported in Alzheimer's disease (AD) and may reflect primary or secondary circuitry degeneration (i.e., due to cortical atrophy). The interpretation of diffusion tensor imaging (DTI) eigenvectors, known as multiple indices, may provide new insights into the main pathological models supporting primary or secondary patterns of WM disruption in AD, the retrogenesis, and Wallerian degeneration models, respectively. The aim of this review is to analyze the current literature on the contribution of DTI multiple indices to the understanding of AD neuropathology, taking the retrogenesis model as a reference for discussion. A systematic review using MEDLINE, EMBASE, and PUBMED was performed. Evidence suggests that AD evolves through distinct patterns of WM disruption, in which retrogenesis or, alternatively, the Wallerian degeneration may prevail. Distinct patterns of WM atrophy may be influenced by complex interactions which comprise disease status and progression, fiber localization, concurrent risk factors (i.e., vascular disease, gender), and cognitive reserve. The use of DTI multiple indices in addition to other standard multimodal methods in dementia research may help to determine the contribution of retrogenesis hypothesis to the understanding of neuropathological hallmarks that lead to AD.
In this review, I argue that this textbook edited by BENNETT and CHECKEL is exceptionally valuable in at least four aspects. First, with regards to form, the editors provide a paragon of how an edited volume should look: well-connected articles "speak to" and build on each other. The contributors refer to and grapple with the theoretical framework of the editors who, in turn, give heed to the conclusions of the contributors. Second, the book is packed with examples from research practice. These are not only named but thoroughly discussed and evaluated for their methodological potential in all chapters. Third, the book aims at improving and popularizing process tracing, but does not shy away from systematically considering the potential weaknesses of the approach. Fourth, the book combines and bridges various approaches to (mostly) qualitative methods and still manages to provide abstract and easily accessible standards for making "good" process tracing. As such, it is a must-read for scholars working with qualitative methods. However, BENNETT and CHECKEL struggle with fulfilling their promise of bridging positivist and interpretive approaches, for while they do indeed take the latter into account, their general research framework remains largely unchanged by these considerations. On these grounds, I argue that, especially for scholars in the positivist camp, the book can function as a "how-to" guide for designing and implementing research. Although this may not apply equally to interpretive researchers, the book is still a treasure chest for them, providing countless conceptual clarifications and potential pitfalls of process tracing practice.
In the last few years, Myanmar has undergone a severe and unexpected change. The military-led country has been starting to open up its borders and economy, enhance citizens’ rights and, allegedly, democratize. While the EU and US were quick to celebrate the changes and lift sanctions in return, a number of questions remain: Will the changes be sustainable? Does the opening-up indicate a movement towards democracy? What were the reasons for the military to relinquish some of its power – and has it actually done so in the first place?
In eukaryotic cells, mitochondria host ancient essential bioenergetic and biosynthetic pathways. LYR (leucine/tyrosine/arginine) motif proteins (LYRMs) of the Complex1_LYR-like superfamily interact with protein complexes of bacterial origin. Many LYR proteins function as extra subunits (LYRM3 and LYRM6) or novel assembly factors (LYRM7, LYRM8, ACN9 and FMC1) of the oxidative phosphorylation (OXPHOS) core complexes. Structural insights into complex I accessory subunits LYRM6 and LYRM3 have been provided by analyses of EM and X-ray structures of complex I from bovine and the yeast Yarrowia lipolytica, respectively. Combined structural and biochemical studies revealed that LYRM6 resides at the matrix arm close to the ubiquinone reduction site. For LYRM3, a position at the distal proton-pumping membrane arm facing the matrix space is suggested. Both LYRMs are supposed to anchor an acyl-carrier protein (ACPM) independently to complex I. The function of this duplicated protein interaction of ACPM with respiratory complex I is still unknown. Analysis of protein-protein interaction screens, genetic analyses and predicted multi-domain LYRMs offer further clues on an interaction network and adaptor-like function of LYR proteins in mitochondria.
Ziel dieser Studie ist eine videobasierte Analyse von Aufgaben im Unterricht zur Erklärung von Variationen des Beteiligungsverhaltens der Schüler/innen im Unterrichtsprozess. In der empirischen Unterrichtsforschung kommt dem Beteiligungsverhalten der Schüler/innen im Unterricht die Rolle einer Schlüsselvariable für die Wirksamkeit von Unterrichtsprozessen zu. Obwohl in theoretischen Modellen effektiven Unterrichts sowie in einer Reihe empirischer Untersuchungen die Qualität des Aufgabenangebots im Unterrichtsprozess als ein wichtiger Einflussfaktor für das Beteiligungsverhalten genannt wird, liegen kaum prozess-sensible Analysen zum Zusammenhang zwischen diesen beiden Geschehenskomponenten des Unterrichts vor. Die vorliegende, primär explorativ ausgerichtete Arbeit nimmt diesen Zusammenhang mittels videobasierter, quantitativ orientierter Verfahren systematischer Beobachtung in den Blick. Dazu wurden in sechs Klassen der 6. Jahrgangsstufe unterschiedlicher Schulformen jeweils vier Unterrichtsstunden des Faches Englisch videographiert. Im Vorfeld wurde mit den Schüler(inne)n (n=145) ein schriftlicher Leistungstest im Unterrichtsfach inklusive Fragen zur Person (Geschlecht und familiärer Sprachhintergrund) durchgeführt, sodass eine Differenzierung der im Unterrichtsprozess untersuchten Effekte nach unterschiedlichen Untergruppen möglich ist. Das Schülerbeteiligungsverhalten, operationalisiert als time on task, wurde mit einem niedrig-inferenten Beobachtungssystem im Intervallkodierungsverfahren erhoben, welches ein zeitlich vollständiges, individualisiertes Verlaufsprofil des Unterrichtsverhaltens aller Schüler/innen in der Klasse erlaubt. Die mittels Ereigniskodierverfahren erfassten Aufgaben wurden mit einem mehrdimensionalen, auf bestehenden Analyseinstrumentarien basierenden Kategoriensystem beschrieben.
In den Ergebnissen zeigt das Geschlecht als einzige Hintergrundvariable der Schüler/innen einen Einfluss auf die individuelle durchschnittliche Verhaltenstendenz im Unterricht. Bezogen auf die Hauptfrage der Studie lassen sich mit Blick in den Unterrichtsverlauf, das heißt auf Ebene der Einzelaufgabe, kaum belastbare Effekte von Variationen der erfassten Aufgabenmerkmale auf das Beteiligungsverhalten der Schüler/innen identifizieren. Bei Betrachtung des Aufgabenangebots auf Stundenebene sind hingegen eine Reihe schwacher bis mittlerer Zusammenhängen zwischen der stundenspezifischen Variabilität der Aufgabenmerkmale und dem durchschnittlichen on task-Niveau in der Klasse feststellbar, wobei sich die meisten dieser Effekte bei Berücksichtung von Untergruppen in der Klasse ausdifferenzieren. Insgesamt ergibt sich aus den vorliegenden Ergebnissen kein eindeutiges Bild zum Zusammenhang zwischen Eigenschaften des Aufgabenangebots im Unterricht und dem Beteiligungsverhalten der Schüler/innen. Die Befunde deuten vielmehr auf die Notwendigkeit zur Fokussierung einzelner Teilaspekte unter Schärfung der Analyseinstrumentarien sowie in Teilen der fokussierten Konstrukte hin. Die vorgelegten Ergebnisse bieten dafür zahlreiche Anschlussstellen und zeigen gleichzeitig Perspektiven zur Weiterentwicklung untersuchungs- bzw. auswertungsmethodischer Vorgehensweisen auf.
Il presente lavoro ha come oggetto d'esame lo scontro del filosofo neo-idealista Giovanni Gentile (1875-1944) col Modernismo cattolico. Obiettivo del lavoro è offrire per la prima volta un esame completo della controversa, durata sei anni, dal 1903 al 1909, attraverso una constestualizzazione storico ecclesiastica e storico filosofica di essa. Il tutto basandosi sulla pubblicazione di inediti fonti d'archivio.
Dissecting the complexities of mammalian heart development and regenerative capacity require thorough understanding of the underlying molecular mechanisms through the expression pattern of proteins and post-translational modifications. To obtain insights intoactivated signaling pathways that control the cellular phenotype during postnatal heart development, we generated a comprehensive map of phosphorylation sites. In total we identified 21,261 phosphorylation sites and 8985 proteins in developing mouse hearts by mass spectrometry. The in-vivo SILAC (stable isotope labeling of amino acids in cell culture) approach allowed robust quantification of phosphorylation sites and proteins, which are regulated during heart development. We found several activated pathways involved in cell cycle regulation and detected numerous kinases and transcription factors to be regulated on protein and phosphopeptide level. Most strikingly, we identified a novel mitochondrial protein, known previously as Perm1, as a highly phosphorylated factor regulated during heart development. We renamed Perm1 as MICOS complex subunit Mic85 since it shows robust physical interaction with MICOS complex subunits, including Mitofilin (Mic60), Chchd3 (Mic19), Chchd6 (Mic25) and the outer membrane protein Samm50. Moreover, Mic85 is localized to the mitochondrial inner membrane facing the intermembrane space and the dynamics of Mic85 protein expression is regulated by the ubiquitin-proteasomal system through phosphorylation of casein kinase 2 on its PEST motif. Silencing of Mic85 in cultured neonatal cardiomyocytes impairs mitochondrial morphology and compromises oxidative capacity. Our findings support a clear role for Mic85 in the maintenance of mitochondrial architecture and in its contribution to enhanced energetics during developing and adult mouse cardiomyocytes. The transgenic Mic85 knockout mouse generated with a GFP knock-in will support future in vivo investigations on the integrity of mitochondria and the function of Mic85 in cardiac development.
Der vorliegende Beitrag gibt einen kurzen Überblick über die wichtigsten Wendepunkte in der zwölf-jährigen Geschichte der Gruppe „Islamischer Staat“ (IS) im Irak. Die andauernden Konflikte in Syrien und Irak haben, neben ihren unmittelbaren humanitären Folgen für die Zivilbevölkerung, auch Auswirkungen auf die globale Ideologie des Dschihadismus und beeinflussen somit indirekt auch andere regionale Konflikte.
Von 2003 bis 2014 war der IS eine von vielen regionalen Gruppen weltweit, die unter der nominellen Führung von al-Qaida am globalen Dschihad teilnahmen. Heute setzt der IS eigene Machtansprüche in Syrien und Irak in direkter Konfrontation mit dem syrischen Ableger der Al-Qaida(Jabhat An-Nusra) durch. Infolge dieser Auseinandersetzung gab Ayman az-Zawahiri im Februar 2014 öffentlich bekannt, dass al-Qaida den IS aus ihrer Organisation ausschließt.
Nicht zuletzt durch diesen Ausschluss war der IS unter der Führung von Abu Bakr al-Baghdadi genötigt den eigenen Führungsanspruch in der Region durch die Ausrufung eines Kalifates nachdrücklich geltend zu machen.
Dies war allerdings keine spontane Entscheidung, denn die Errichtung eines Kalifats war ein Plan, den Baghdadis Gruppe seit vielen Jahren mit großem Aufwand verfolgte.
Durch das Zerwürfnis zwischen dem IS und der afghanisch-pakistanischen al-Qaida teilt sich die globale dschihadistische Bewegung nun in zwei Einflussreiche Einheiten.
Part IV of our series on ISIS : "Blogforum 'Kalifat des Terrors: Interdisziplinäre Perspektiven auf den Islamischen Staat".
One element within US counter-terrorism strategies is “reducing terrorist group cohesion”, as the think tank RAND recommends in one of its reports. The Combating Terrorism Center at West Point (CTC) puts these recommendations into actions. Reports like ”Cracks in the Foundation” or ”Dysfunction and Decline” vividly depict the internal disagreement and disunity between al-Qaeda central (AQ) and its regional affiliates, most of all AQ in Iraq (AQI). Albeit these reports are drafted by pundits and certainly provide meaningful and often rare insights into the inner life of the global jihadi movement, they also serve another purpose: to deliberately amplify the very same trend they describe: disunity...
We consider the continuous-time portfolio optimization problem of an investor with constant relative risk aversion who maximizes expected utility of terminal wealth. The risky asset follows a jump-diffusion model with a diffusion state variable. We propose an approximation method that replaces the jumps by a diffusion and solve the resulting problem analytically. Furthermore, we provide explicit bounds on the true optimal strategy and the relative wealth equivalent loss that do not rely on quantities known only in the true model. We apply our method to a calibrated affine model. Our findings are threefold: Jumps matter more, i.e. our approximation is less accurate, if (i) the expected jump size or (ii) the jump intensity is large. Fixing the average impact of jumps, we find that (iii) rare, but severe jumps matter more than frequent, but small jumps.
Background & aim: Whether inosine triphosphatase (ITPA) gene polymorphisms predict anemia during interferon-free therapy in chronic hepatitis C virus (HCV)-infected patients is unknown. We examined the relationship between two ITPA polymorphisms, anemia, and sustained virological response 12 weeks post-treatment (SVR12) in patients receiving the NS3/4A protease inhibitor faldaprevir, the non-nucleoside polymerase inhibitor deleobuvir, and ribavirin.
Methods: HCV genotype 1-infected, treatment-naïve patients (N = 362) were randomized and treated in one of five treatment arms with faldaprevir and deleobuvir with or without ribavirin. Two ITPA polymorphisms (rs1127354 and rs6051702) were genotyped and defined as ITPA-deficient (rs1127354 AA or AC; rs6051702 CC or CA) or ITPA-non-deficient (rs1127354 CC; rs6051702 AA) according to their association with ITPA deficiency. Baseline and on-treatment variables associated with anemia and SVR12 were identified using logistic regression.
Results: In the pooled ribavirin-containing arms, 10.1% (32/316) of patients experienced on-treatment hemoglobin <10 g/dL, and 32.6% (103/316) experienced on-treatment hemoglobin <10 g/dL or a change from baseline ≥3.5 g/dL. Of the latter group, 99% (102/103) had the ITPA-non-deficient rs1127354 genotype. Other variables associated with on-treatment hemoglobin <10 g/dL or a decrease ≥3.5 g/dL were age, baseline hemoglobin, rs6051702 genotype, and plasma ribavirin concentration. In a multivariate analysis, high plasma ribavirin concentration, low baseline hemoglobin, HCV genotype 1b, and IL28B genotype CC were associated with higher SVR12.
Conclusions: The ITPA rs1127354 CC and rs6051702 AA genotypes may predict ribavirin-induced anemia during treatment with interferon-free, ribavirin-containing regimens. With this interferon-free regimen, SVR was associated with ribavirin levels, but not with anemia or ITPA genotypes.
La tradizione funeraria dell’isola di Cipro prevede fin da età Geometrica ed Arcaica l’utilizzo di sepolture di tipo rupestre, in modo particolare di camere ipogee ricavate solitamente al di sotto del banco roccioso, che possono essere viste come uno sviluppo delle tombe a camera dell'età del Bronzo. A partire dalla fase di transizione da età Classica ad età Ellenistica, con la presenza tolemaica nell'isola, vengono importati nuovi modelli e le camere vengono regolarizzate e dotate di elementi "monumentali" interni. In questa sede si analizzano le tipologie della loculus chamber e le attestazioni di utilizzo dell'arcosolium nell'area delle antiche città di Paphos e Kourion.
Im Zuge des Arabischen Frühlings 2011 konnte sich der sogenannte „Islamische Staat“ (IS) zu einer erfolgreichen und gefährlichen islamistischen Organisation im Nahen Osten entwickeln. Der IS nutze die politisch instabile Lage in den arabischen Ländern, um an Macht und Einfluss zu gewinnen und schaffte es, mehrere syrische Regionen unter seine Kontrolle zu bringen. Da die eroberten Regionen in Syrien und Irak direkt oder unmittelbar entlang der türkischen Grenze verlaufen, gerieten auch Abschnitte der türkisch-syrischen Grenze unter die Kontrolle des IS. Die Eroberungen unter anderem ar-Raqqas in Syrien bis einschließlich Falludschas, Kerküks und Diyales im Norden Iraks spiegeln den Erfolg des IS wider. Dieser Erfolg wirkt attraktiv für viele jihadistische Sympathisanten weltweit, weshalb die Gruppe in kurzer Zeit rasant wuchs und noch wächst. Dem International Centre for the Study of Radicalisation and Political Violence (ICSR) zufolge fanden im November 2014 allein aus Europa rund 4.300 Männer und Frauen den Weg zum IS.1 Die meisten von ihnen reisten über das Nachbarland Türkei ein. Jihadisten aus Deutschland nehmen beispielsweise den Bus, die Fähre oder das Flugzeug nach Istanbul. Auf Bus- und Fährfahrten werden die Fahrgäste in den Durchfahrtsländern des Schengener Abkommens nicht und außerhalb des Schengen-Raums kaum kontrolliert. In der 14-Millionen-Metropole Istanbul angekommen, fahren sie mit öffentlichen Verkehrsmitteln weiter quer durch die Türkei in den Südosten des Landes.
Die Reisenden werden an ausgewählte Grenzbereiche gebracht, die kaum kontrolliert werden können.2 Die 900 km lange Grenze ermöglicht ihnen eine problemlose Überquerung nach Syrien. Staatspräsident Recep Tayyip Erdoğan weist darauf hin, dass eine lückenlose Überwachung einer Grenze in dieser Länge nicht zu gewährleisten sei. Allerdings wurde von Repräsentanten europäischer Länder, der USA und aus den Reihen der türkischen Opposition wiederholt der Verdacht geäußert, dass die türkische Regierung mit dem IS kooperiere. Dies aufgreifend stehen im Fokus dieses Artikels folgenden Fragen: Worauf basieren diese Behauptungen und wie geht die türkische Regierung damit um?
The aim of this study was to identify sex-dependent expression of renal transporter mRNA in lean and obese Zucker spontaneously hypertensive fatty (ZSF1) rats and to investigate the interaction of the most altered transporter, organic anion transporter 2 (Oat2), with diabetes-relevant metabolites and drugs. Higher incidence of glomerulosclerosis, tubulointerstitial fibrosis, and protein casts in Bowman’s space and tubular lumen was detected by PAS staining in obese male compared to female ZSF1 rats. Real-time PCR on RNA isolated from kidney cortex revealed that Sglt1-2, Oat1-3, and Oct1 were higher expressed in kidneys of lean females. Oct2 and Mrp2 were higher expressed in obese males. Renal mRNA levels of transporters were reduced with diabetic nephropathy in females and the expression of transcription factors Hnf1β and Hnf4α in both sexes. The highest difference between lean and obese ZSF1 rats was found for Oat2. Therefore, we have tested the interaction of human OAT2 with various substances using tritium-labeled cGMP. Human OAT2 showed no interaction with diabetes-related metabolites, diabetic drugs, and ACE-inhibitors. However, OAT2-dependent uptake of cGMP was inhibited by furosemide. The strongly decreased expression of Oat2 and other transporters in female diabetic ZSF1 rats could possibly impair renal drug excretion, for example, of furosemide.
In an experimental setting in which investors can entrust their money to traders, we investigate how compensation schemes affect liquidity provision and asset prices. Investors face a trade-off between risk and return. At the benefit of a potentially higher return, they can entrust their money to a trader. However this investment is risky, as the trader might not be trustworthy. Alternatively, they can opt for a safe but low return. We study how subjects solve this trade-off when traders are either liable for losses or not, and when their bonuses are either capped or not. Limited liability introduces a conflict of interest because it makes traders value the asset more than investors. To limit losses, investors should thus restrict liquidity provision to force traders to trade at a lower price. By contrast, bonus caps make traders value the asset less than investors. This should encourage liquidity provision and decrease prices. In contrast to these predictions, we find that under limited liability investors contribute to asset price bubbles by increasing liquidity provision and that caps fail to tame bubbles. Overall, giving investors skin in the game fosters financial stability.
Do markets correct individual behavioral biases? In an experimental asset market, we compare the outcomes of a standard market economy to those of a an island economy that removed market interactions. We observe asset price bubbles in the market economy while prices are stable in the island economy. We also find that subjects took more risk following larger losses, resulting in larger prices and consistent with a gambling for resurrection motive. This motive can translate into bubbles in the market economy because higher prices increase average losses and thus reinforce the desire to resurrect. By contrast, the absence of such a strategic complementarity in island economies can explain the more stable outcome. These results suggest that markets do not correct behavioral biases, rather the contrary.
We investigate the relationship between anchoring and the emergence of bubbles in experimental asset markets. We show that setting a visual anchor at the fundamental value (FV) in the first period only is sufficient to eliminate or to significantly reduce bubbles in laboratory asset markets. If no FV-anchor is set, bubble-crash patterns emerge. Our results indicate that bubbles in laboratory environments are primarily sparked in the first period. If prices are initiated around the FV, they stay close to the FV over the entire trading horizon. Our insights can be related to initial public offerings and the interaction between prices set on pre-opening markets and subsequent intra-day price dynamics.
Mit der Optogenetik hat sich in der Neurowissenschaft eine Revolution vollzogen. Die Optogenetik erlaubt, Nervenzellen einfach mit Licht und mit bis dato nicht gekannter Genauigkeit zeitlich und räumlich elektrodenfrei an- und abzuschalten. Dies wird durch das Einbringen genetisch codierter Lichtschalter, sogenannter mikrobieller Rhodopsine, in den Nervenzellen erreicht. Die Methode, die in Frankfurt und in Regensburg ihren Ursprung genommen hat, wird heute in der Neurobiologie weltweit eingesetzt. Neben der Grundlagenforschung eröffnen sich dank der Optogenetik auch neue biomedizinische Perspektiven zur Gentherapie neurodegenerativer Krankheiten.
Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+), cytotoxic-T cells (CD8+), T-helper cells (CD4+), B cells (CD20+), macrophages (CD68+), mast cells (CD117+), mononuclear cells (CD11c+), plasma cells, activated-T cells (MUM1+), B cells, myeloid cells (PD1+) and neutrophilic granulocytes (myeloperoxidase+) compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells) in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.
Seit mehr als 200 Jahren gibt es durch die Wissenschaftler der Wetterstation auf dem Hohenpeißenberg systematische Wetterbeobachtungen, doch erst seit wenigen Jahren gibt es unter den Klimaforschern einen Konsens, dass sich das Klima durch anthropogene Einflüsse schon verändert hat – und weiter verändern wird. Die bisherigen Auswirkungen, wie zum Beispiel ein globaler Temperaturanstieg von 0,85°C seit Beginn der Industrialisierung, sind heute gut belegbar. Mögliche zukünftige Entwicklungen des Klimas werden heute ebenso erforscht wie die Auswirkungen des Klimawandels auf Mensch und Umwelt. Zu diesen Auswirkungen gehören unter anderem Folgen für die Landwirtschaft. Durch veränderte Niederschläge und den Temperaturanstieg werden sich die Lebensbedingungen von Bodenorganismen und Anbaubedingungen für Pflanzen ändern. Letztendlich ist aufgrund dieser Veränderungen auch ein verstärkter Einsatz von Pestiziden zu erwarten. Allerdings wurde bisher kaum untersucht, ob der Einsatz von Pestiziden in der Landwirtschaft unter den Bedingungen des Klimawandels (konkret durch die Interaktion von klimatischen und chemischen Faktoren) ein erhöhtes Umweltrisiko für Bodenorganismen darstellt. Bisher werden klimatische Faktoren bei den Tests für die Zulassung von Pestiziden nicht berücksichtigt.
Daher wurde diese Fragestellung in der hier vorliegenden Dissertation am Beispiel der Effekte von zwei zugelassenen Pestiziden auf Bodenorganismen unter verschiedenen klimatischen Bedingungen untersucht. Konkret wurden dazu mit Labor- und Halbfreilandversuchen die Wirkung eines Insektizids und eines Fungizids in Interaktion von Temperatur und Bodenfeuchte auf Vertreter zweier Invertebratengruppen (Collembola: zwei Arten; Enchytraeidae: eine Art) untersucht.
In einem modifizierten Standardtest mit Collembolen erhöhte sich die Toxizität des Insektizids Lambda-Cyhalothrin, wenn die Exposition der beiden Arten bei einer erhöhten Bodenfeuchte stattfindet. Die kühl adaptierte Art Folsomia candida reagierte bei erhöhter Testtemperatur am empfindlichsten auf diese Testsubstanz: Die EC50 aus diesem Experiment lag bei 2,84 mg (a.s.)/kg Boden Trockengewicht (dw). Unter Standardbedingungen, wie sie in Tests für die Zulassung von Pestiziden angewandt werden, lag die EC50 von F. candida dagegen bei 8,65 mg a.s./kg dw.
Unter den gleichen Versuchsbedingungen wurde auch das Fungizid Pyrimethanil an Collembolen getestet. Hier erwies sich die Testsubstanz für beide Arten bei
gleichzeitigem Trockenstress und / oder erhöhter Temperatur als toxischer im Vergleich zu den Standard-Testbedingungen. Dabei zeigte F. candida mit einer EC50 von 28,3 mg a.s./kg dw die höchste Empfindlichkeit. Ohne die veränderten klimatischen Faktoren, betrug die EC50 von F. candida 52,3 mg a.s./kg dw.
In Reproduktionstests mit der Enchytraeen-Art Enchytraeus bigeminus wurde die Bodenfeuchte als klimatischer Faktor in Kombination mit jeweils einer Testsubstanz untersucht. Bei beiden Chemikalien reagierte E. bigeminus in trockenem Boden empfindlicher. Die ermittelten EC50 betrugen 1,34 mg a.s./kg dw für Lambda-Cyhalothrin und 437 mg a.s./kg dw für Pyrimethanil. Getestet unter Standardbedingungen lagen die EC50-Werte bei 3,79 bzw. 499 mg a.s./kg dw.
Neben den Laborexperimenten wurden Tests in „Terrestrischen Modellökosystemen“ (TME) mit den gleichen Chemikalien in Kombination mit variierender Bodenfeuchte als klimatischer Faktor vorgenommen. Diese Experimente wurden in Deutschland und in Portugal durchgeführt, um die Reaktion einer zentraleuropäischen und einer mediterranen Artengemeinschaft zu untersuchen. Aus der terrestrischen Lebensgemeinschaft wurden verschiedene Organismengruppen untersucht. Die Effekte auf Enchytraeen aus dem Experiment mit Pyrimethanil waren als Veröffentlichung Teil dieser Dissertation. In der portugiesischen Halbfreilandstudie wurden keine Effekte auf die Enchytraeen durch Pyrimethanil bei umweltrelevanten Konzentrationen festgestellt, jedoch beeinflusste die Bodenfeuchte die Zusammensetzung der Artengemeinschaft. Im deutschen TME-Experiment wurde eine verstärkte Wirkung des Fungizids in trockenem Boden festgestellt, d.h. die jeweiligen Effektkonzentrationen (niedrigste EC50 3,48 mg a.s./kg dw für Fridericia connata in trockenem Boden) lagen deutlich unterhalb der aus den Labortests mit Enchytraeus bigeminus bekannten Werten (499 mg a.s./kg dw).
Zusammenfassend lässt sich feststellen, dass klimatische Faktoren die Effekte von Pflanzenschutzmittel auf Bodenorganismen beeinflussen können. Für Laborversuche ist eine generelle Berücksichtigung von klimatischen Faktoren im Zulassungsverfahren aus heutiger Sicht zu weit gegriffen. Die TME-Versuche zeigten sich als geeignetes Testverfahren, interaktive Effekte von Pestiziden und Klima bzw. multiplen Stressoren generell auf Artengemeinschaften zu untersuchen. Für TME-Experimente wäre unter Beachtung der Vielzahl möglicher Fragestellungen, Endpunkte und moderner statistischer Auswerteverfahren eine internationale Richtlinie wünschenswert.
We examine firms’ simultaneous choice of investment, debt financing and liquidity in a large sample of US corporates between 1980 and 2014. We partition the sample according to the firms’ financial constraints and their needs to hedge against future shortfalls in operating income. In contrast to earlier work, our joint estimation approach shows that cash flows affect the corporate decisions of unconstrained firms more strongly than those of constrained firms. Investment-cash flow sensitivities are particularly intense for unconstrained firms with high hedging needs. Investment opportunities (as proxied by Q), however, play a larger role for constrained firms with the effects being strongest in case of low hedging needs. Interestingly, constrained firms with low hedging needs are found to employ more debt to finance their investment opportunities and build up significant cash holdings at the same time. Our results hence indicate overinvestment behavior for unconstrained firms but no underinvestment for constrained firms if they have low hedging needs.
Despite multimodal regimens and diverse treatment options alleviating disease symptoms, morbidity and mortality associated with advanced ischemic heart failure remain high. Recently, technological innovation has led to the development of regenerative therapeutic interventions aimed at halting or reversing the vicious cycle of heart failure progression. Driven by the unmet patient need and fueled by encouraging experimental studies, stem cell-based clinical trials have been launched over the past decade. Collectively, these trials have enrolled several thousand patients and demonstrated the clinical feasibility and safety of cell-based interventions. However, the totality of evidence supporting their efficacy in ischemic heart failure remains limited. Experience from the early randomized stem cell clinical trials underscores the key points in trial design ranging from adequate hypothesis formulation to selection of the optimal patient population, cell type and delivery route. Importantly, to translate the unprecedented promise of regenerative biotherapies into clinical benefit, it is crucial to ensure the appropriate choice of endpoints along the regulatory path. Accordingly, we here provide considerations relevant to the choice of endpoints for regenerative clinical trials in the ischemic heart failure setting.
In the ‘age of transnationalization’, spatial mobility is highly valued as a resource and accordingly ‘sedentariness’ is often symbolically devalued. Migration between Poland and Germany (mainly from Poland to Germany) has a century-long tradition. Not only has it yielded the emergence of a dense transnational social space, but is also considered as a re-enactor of cultural traits and symbolic meanings. Spatial mobility is tied to notions of social mobility and to projects of life-making. Since legal restrictions for Polish migrants seeking to work and settle in Germany have vanished, the quest for ‘normalcy’ has enhanced and pressures towards even more migration have increased. I argue that symbolic meanings of mobility are decisive for hierarchies in transnational social spaces. I have put main emphasize on families’ practices of caring for and caring about each other: the first being more a physical or material activity, while the latter is a more symbolic and emotional one. The interviews reveal that people draw multiple differentiations between migrant populations in terms of their migration reasons as well as between the mobile and the immobile. Those differentiations are embedded in the distinct feature of the transnational social space between Poland and Germany with assumed differences in terms of ‘modernity’. At the end the symbolic meanings of mobility also help explain the puzzle of why the emigration rates from Poland are constantly high, although Poland is a comparatively wealthy country.
Dieser Beitrag ist ein Besprechungsaufsatz zu Beatrice Brunhöbers 2010 erschienener Dissertation Die Erfindung „demokratischer Repräsentation“ in den Federalist Papers (Mohr Siebeck, Tübingen: Grundlagen der Rechtswissenschaft, Bd. 14), in der Brunhöber die innovative – und auch die Verfassungsentwicklung andernorts prägende – Kraft der Verbindung von Demokratie, politischer Repräsentation und Föderalismusidee durch die amerikanischen Verfassungsväter herausarbeitet. Auf der Basis von Brunhöbers Untersuchung geht es insbesondere darum, wie sich das von Hamilton, Madison und Jay entworfene ‚alte‘ Konzept zur Gestaltung eines starken Gemeinwesens (eingeschlossen das vertrauensbildende Prinzip der Gewaltenteilung) für einen integrativen Umgang mit den ‚modernen‘ Gegebenheiten pluralistischer Gesellschaften nutzbar machen läßt, im Blick die Gesamtheit (und Vielfalt) des Staatsvolkes als Geltungsfundament legitimer Herrschaft. Im Hintergrund steht die Frage nach Möglichkeiten zur Nutzbarmachung historischer Vergewisserungen für heutige Debatten überhaupt.
Hepatitis B caused by infection with the hepatitis B virus (HBV) still ranks among the most challenging infectious diseases of our time. Despite the availability of an effective prophylactic vaccine, 240 million people worldwide are estimated to be chronically infected with HBV and are at risk of developing life-threatening liver diseases, including cirrhosis and liver cancer. The underlying pathogenic mechanisms of HBV-associated liver diseases are only incompletely understood. It is widely accepted that liver pathology results from long-term immune-mediated liver injury and inflammation as a consequence of inefficient viral elimination. This injury can be naturally compensated by liver regeneration. However, chronic liver damage and permanent inflammation debilitates the regenerative capacity of the liver and fosters fibrosis as well as accumulation of chromosomal aberrations, which both contribute to cirrhosis and liver cancer. Liver regeneration requires the presence of the redox-sensitive transcription factor Nrf2 and intact insulin receptor signaling. A lack of Nrf2 causes increased intracellular levels of reactive oxygen species (ROS) that inactivate insulin receptor signaling and induce insulin resistance. Interestingly, HBV was observed to activate Nrf2 and the expression of Nrf2-regulated genes. This argues against an inhibitory effect of HBV on insulin receptor signaling by increased ROS levels. However, chronic HBV infection is associated with dysregulation of hepatocyte proliferation and retardation of liver regeneration. Hence, the aim of this thesis was to investigate the influence of HBV on the process of liver regeneration with respect to the insulin receptor signaling pathway. After short-term carbon tetrachloride (CCl4)-induced liver damage, HBV transgenic mice present prolonged liver damage and impaired liver regeneration as reflected by reduced hepatocyte proliferation and increased apoptosis. Impaired hepatocyte proliferation in HBV transgenic mice correlates with diminished activation of the insulin receptor. It was further observed in vitro that the activation of Nrf2 by HBV induces increased levels of the insulin receptor mRNA and protein in HBV-expressing cells. Strikingly, stably HBV-expressing cells as well as primary mouse hepatocytes from HBV transgenic mice bind less insulin due to reduced amounts of insulin receptor on the cell surface. This is caused by intracellular retention of the insulin receptor in HBV-expressing cells as a consequence of increased amounts of the cellular trafficking factor α-taxilin. The reduced amounts of insulin receptor on the cell surface impair insulin sensitivity in HBV-expressing cells and inactivate downstream signaling cascades that initiate insulin-dependent gene expression and glucose uptake. As a consequence of impaired hepatocyte proliferation and liver regeneration, HBV transgenic mice exhibit increased development of fibrosis after long-term CCl4-induced liver damage. Taken together, in this thesis, a novel pathomechanism could be uncovered that includes inactivation of insulin receptor signaling by HBV via intracellular retention of the insulin receptor leading to impaired liver regeneration after liver damage and promotion of liver fibrosis. These findings significantly contribute to an enhanced understanding of HBV-associated liver pathogenesis.
The forest, savanna, and grassland biomes, and the transitions between them, are expected to undergo major changes in the future due to global climate change. Dynamic global vegetation models (DGVMs) are very useful for understanding vegetation dynamics under the present climate, and for predicting its changes under future conditions. However, several DGVMs display high uncertainty in predicting vegetation in tropical areas. Here we perform a comparative analysis of three different DGVMs (JSBACH, LPJ-GUESS-SPITFIRE and aDGVM) with regard to their representation of the ecological mechanisms and feedbacks that determine the forest, savanna, and grassland biomes, in an attempt to bridge the knowledge gap between ecology and global modeling. The outcomes of the models, which include different mechanisms, are compared to observed tree cover along a mean annual precipitation gradient in Africa. By drawing on the large number of recent studies that have delivered new insights into the ecology of tropical ecosystems in general, and of savannas in particular, we identify two main mechanisms that need improved representation in the examined DGVMs. The first mechanism includes water limitation to tree growth, and tree–grass competition for water, which are key factors in determining savanna presence in arid and semi-arid areas. The second is a grass–fire feedback, which maintains both forest and savanna presence in mesic areas. Grasses constitute the majority of the fuel load, and at the same time benefit from the openness of the landscape after fires, since they recover faster than trees. Additionally, these two mechanisms are better represented when the models also include tree life stages (adults and seedlings), and distinguish between fire-prone and shade-tolerant forest trees, and fire-resistant and shade-intolerant savanna trees. Including these basic elements could improve the predictive ability of the DGVMs, not only under current climate conditions but also and especially under future scenarios.
Some observers have conjectured that oil supply shocks in the United States and in other countries are behind the plunge in the price of oil since June 2014. Others have suggested that a major shock to oil price expectations occurred when in late November 2014 OPEC announced that it would maintain current production levels despite the steady increase in non-OPEC oil production. Both conjectures are perfectly reasonable ex ante, yet we provide quantitative evidence that neither explanation appears supported by the data. We show that more than half of the decline in the price of oil was predictable in real time as of June 2014 and therefore must have reflected the cumulative effects of earlier oil demand and supply shocks. Among the shocks that occurred after June 2014, the most influential shock resembles a negative shock to the demand for oil associated with a weakening economy in December 2014. In contrast, there is no evidence of any large positive oil supply shocks between June and December. We conclude that the difference in the evolution of the price of oil, which declined by 44% over this period, compared with other commodity prices, which on average only declined by about 5%-15%, reflects oil-market specific developments that took place prior to June 2014.
Although there is much interest in the future retail price of gasoline among consumers, industry analysts, and policymakers, it is widely believed that changes in the price of gasoline are essentially unforecastable given publicly available information. We explore a range of new forecasting approaches for the retail price of gasoline and compare their accuracy with the no-change forecast. Our key finding is that substantial reductions in the mean-squared prediction error (MSPE) of gasoline price forecasts are feasible in real time at horizons up to two years, as are substantial increases in directional accuracy. The most accurate individual model is a VAR(1) model for real retail gasoline and Brent crude oil prices. Even greater reductions in MSPEs are possible by constructing a pooled forecast that assigns equal weight to five of the most successful forecasting models. Pooled forecasts have lower MSPE than the EIA gasoline price forecasts and the gasoline price expectations in the Michigan Survey of Consumers. We also show that as much as 39% of the decline in gas prices between June and December 2014 was predictable.
Anleihen werden in der Regel in zahlreiche Teilschuldverschreibungen aufgespalten und diese an verschiedene Investoren verkauft. Dies begründet, der Zahl der umlaufenden Teilschuldverschreibungen entsprechend, jeweils unterschiedliche Schuldverhältnisse zwischen dem Emittenten und dem jeweiligen Investor. Hält ein Investor mehrere Teilschuldverschreibungen, so entstehen dementsprechend mehrere rechtlich voneinander zu unterscheidende Schuldverhältnisse mit gleichem Inhalt.1 Diese können jeweils ein unterschiedliches rechtliches Schicksal haben, z. B. getrennt voneinander übertragen werden. Sie können auch, von atypischen Gestaltungen abgesehen, je einzeln vom Gläubiger gekündigt werden, wenn die Anleihebedingungen insoweit keine Vorkehrungen treffen. Die folgenden Bemerkungen dazu befassen sich zunächst mit der umstrittenen Frage, ob auch eine Kündigung aus wichtigem Grund seitens eines Gläubigers gemäß §§ 490 Abs. 1, 314 BGB in Betracht kommt (im Folgenden I. - VII.)
O presente artigo explora os principais conceitos que compõe a teoria do reconhecimento de Axel Honneth, a fim de compreender os propósitos imbricados na idéia de luta por reconhecimento e suas contribuições à nova concepção de identidade surgida a partir da modernidade. No padrão pós-convencional, apresentado por Honneth, o indivíduo é reconhecido em sua individualidade. A identidade subjetiva é constituída de forma intersubjetiva e não mais determinada pelo grupo social. O reconhecimento recíproco é condição para a formação prática da identidade, permitindo ao sujeito participar efetivamente na esfera pública. Contudo, por possuir uma estrutura fundamentalmente intersubjetiva, a identidade individual e coletiva é afetada negativamente pelas diferentes situações de desrespeito presente nos processos de interação social. A negação do reconhecimento de modo injustificado, por meio da violação de expectativas normativas de comportamento, da origem a reações emocionais negativas. Por este motivo, as experiências de desrespeito integram a base motivacional da luta por reconhecimento, dando origem ao conflito social. O tema do conflito em Honneth está vinculado aos processos de formação da identidade prática do sujeito e aos progressos na vida social. O conflito social, traduzido na forma de luta por reconhecimento, caracteriza-se como uma expressão altamente positiva, por contribuir significativamente com a autorrealização individual e coletiva.
The global financial crisis (as well as the European sovereign debt crisis) has led to a substantial redesign of rules and institutions – aiming in particular at underwriting financial stability. At the same time, the crisis generated a renewed interest in properly appraising systemic financial vulnerabilities. Employing most recent data and applying a variety of largely only recently developed methods we provide an assessment of indicators of financial stability within the Euro Area. Taking a “functional” approach, we analyze comprehensively all financial intermediary activities, regardless of the institutional roof – banks or non-bank (shadow) banks – under which they are conducted. Our results reveal a declining role of banks (and a commensurate increase in non-bank banking). These structural shifts (between institutions) are coincident with regulatory and supervisory reforms (implemented or firmly anticipated) as well as a non-standard monetary policy environment. They might, unintendedly, actually imply a rise in systemic risk. Overall, however, our analyses suggest that financial imbalances have been reduced over the course of recent years. Hence, the financial intermediation sector has become more resilient. Nonetheless, existing (equity) buffers would probably not suffice to face substantial volatility shocks.
Heavy-ion collisions at ultra-relativistic energies allow access to the Quark-Gluon Plasma, the deconfined phase of the strong interaction, a state which is believed to have existed fractions of seconds after the big bang. Two-particle correlations at small relative momenta, and particularly their dependence on pair transverse mass, are distinctly sensitive to the reaction dynamics of the fireball created in heavy-ion collisions.
Being the heaviest system to extract a size of the particle emitting source, proton-lambda correlations extend the studied range in pair transverse mass and are therefore well suited to explore the dynamical behavior of the matter created in Pb-Pb collisions at the Large Hadron Collider. The centrality dependence of the extracted source radii affirms the expectations of a larger source for more central collisions. Source radii were attained over a span of more than 0.9 GeV/c2 in mean pair transverse mass with a source radius extracted for a mean transverse mass as high as 2.18 GeV/c2. The source radii decrease with increasing pair transverse mass, as expected in a hydrodynamical picture. The comparison with radii obtained from other particle species exhibits the clear breaking of an elsewhere proposed scaling behavior of source radii with mean pair transverse mass for all particle species.
Gamma-gamma correlations possibly allow to look past the barrier of kinetic freeze-out. Additionally, they bear the potential to solve the puzzling observation in heavy-ion collisions of an excess of photons with a large temperature-like inverse slope parameter on the one hand and an elliptic flow coefficient of photons comparable to the one of hadrons on the other hand. A striking signal in the two-photon correlation function is observed; however it seems likely to not be of quantum statistical origin. A path for further studies is laid out.
[Nachruf] Burkhardt Lindner
(2015)
Die vorliegende Arbeit untersuchte die Chancen und Restriktivitäten einer künstlerischen Ausbildung. Welche Möglichkeiten stehen einer künstlerischen Ausbildung zur Verfügung und welchen Grenzen steht sie unüberwindlich gegenüber? Diese waren konstitutionstheoretisch zu entfalten und wissenschaftspraktisch anhand von mir erhobenem Datenmaterial (vornehmlich Interviews mit Studenten und Professoren von Kunsthochschulen in Deutschland) zu belegen bzw. zu verdichten...
The transition to a future electricity system based primarily on wind and solar PV is examined for all regions in the contiguous US. We present optimized pathways for the build-up of wind and solar power for least backup energy needs as well as for least cost obtained with a simplified, lightweight model based on long-term high resolution weather-determined generation data. In the absence of storage, the pathway which achieves the best match of generation and load, thus resulting in the least backup energy requirements, generally favors a combination of both technologies, with a wind/solar PV (photovoltaics) energy mix of about 80/20 in a fully renewable scenario. The least cost development is seen to start with 100% of the technology with the lowest average generation costs first, but with increasing renewable installations, economically unfavorable excess generation pushes it toward the minimal backup pathway. Surplus generation and the entailed costs can be reduced significantly by combining wind and solar power, and/or absorbing excess generation, for example with storage or transmission, or by coupling the electricity system to other energy sectors.
Breast cancer is fast becoming the leading cause of oncologic morbidity and mortality among women worldwide. Demographic changes in Asia, Southeast Asia, and South America will further accelerate this trend. Different specialties are involved in the treatment of breast cancer patients: gynecology, surgery, pathology, hematology/oncology, radiology, radiation oncology, and nuclear medicine. Optimal results are seen in countries providing standardized breast cancer care in certified breast centers. The present article provides an overview of current state-of-the-art treatment strategies and explains the contributions of different specialties to optimal and individualized care for breast cancer patients. Breast cancer will be one of the most important health issues facing physicians involved with women’s health and a basic understanding of current treatment objectives will be essential medical knowledge for everyone taking care of female patients.
Objectives: The aim of our study was to find out how much energy is applicable in second-generation dual source high-pitch computed tomography (CT) in imaging of the abdomen.
Materials and methods: We examined an upper abdominal phantom using a Somatom Definition Flash CT-Scanner (Siemens, Forchheim, Germany). The study protocol consisted of a scan-series at 100 kV and 120 kV. In each scan series we started with a pitch of 3.2 and reduced it in steps of 0.2, until a pitch of 1.6 was reached. The current was adjusted to the maximum the scanner could achieve. Energy values, image noise, image quality, and radiation exposure were evaluated.
Results: For a pitch of 3.2 the maximum applicable current was 142 mAs at 120 kV and in 100 kV the maximum applicable current was 114 mAs. For conventional abdominal imaging, current levels of 200 to 260 mAs are generally used. To achieve similar current levels, we had to decrease the pitch to 1.8 at 100 kV - at this pitch we could perform our imaging at 204 mAs. At a pitch of 2.2 in 120 kV we could apply a current of 206 mAs.
Conclusion: We conclude our study by stating that if there is a need for a higher current, we have to reduce the pitch. In a high-pitch dual source CT, we always have to remember where our main focus is, so we can adjust the pitch to the energy we need in the area of the body that has to be imaged, to find answers to the clinical question being raised.
In this paper, we examine how the institutional design affects the outcome of bank bailout decisions. In the German savings bank sector, distress events can be resolved by local politicians or a state-level association. We show that decisions by local politicians with close links to the bank are distorted by personal considerations: While distress events per se are not related to the electoral cycle, the probability of local politicians injecting taxpayers’ money into a bank in distress is 30 percent lower in the year directly preceding an election. Using the electoral cycle as an instrument, we show that banks that are bailed out by local politicians experience less restructuring and perform considerably worse than banks that are supported by the savings bank association. Our findings illustrate that larger distance between banks and decision makers reduces distortions in the decision making process, which has implications for the design of bank regulation and supervision.
This Paper gives an overview of the German banking system and current challenges it is facing. It starts with an overview of the so-called ‘Three-Pillar-Banking-System’ and a detailed description of the current structure of the banking system in Germany. A brief comparison of the banking system in Germany with the ones in other European countries points out its uniqueness. The consequences of the financial crisis of 2007/2008 and further challenges for the German banking system are discussed, as well as the the ongoing debate around the question whether the strong government involvement should be sustained.
Lernen im fiktiven Strafprozess : Jura-Studierende der Goethe-Uni nehmen an »Moot Court« teil
(2015)
Unter der Leitung von Prof. Dr. Matthias Jahn (Goethe-Universität und im zweiten Hauptamt Richter am OLG Frankfurt) sowie des Rechtsanwalts und wissenschaftlichen Mitarbeiters des Lehrstuhls, Fabian Meinecke, hatten Frankfurter Studierende erstmals die Gelegenheit, selbst in die Robe eines Staatsanwalts oder Strafverteidigers zu schlüpfen – und das ist wörtlich zu verstehen. Marcel Behrendt und Bastian Schmack berichten von ihren Erfahrungen.
Background: Microarray analysis represents a powerful way to test scientific hypotheses on the functionality of cells. The measurements consider the whole genome, and the large number of generated data requires sophisticated analysis. To date, no gold-standard for the analysis of microarray images has been established. Due to the lack of a standard approach there is a strong need to identify new processing algorithms.
Methods: We propose a novel approach based on hyperbolic partial differential equations (PDEs) for unsupervised spot segmentation. Prior to segmentation, morphological operations were applied for the identification of co-localized groups of spots. A grid alignment was performed to determine the borderlines between rows and columns of spots. PDEs were applied to detect the inflection points within each column and row; vertical and horizontal luminance profiles were evolved respectively. The inflection points of the profiles determined borderlines that confined a spot within adapted rectangular areas. A subsequent k-means clustering determined the pixels of each individual spot and its local background.
Results: We evaluated the approach for a data set of microarray images taken from the Stanford Microarray Database (SMD). The data set is based on two studies on global gene expression profiles of Arabidopsis Thaliana. We computed values for spot intensity, regression ratio, and coefficient of determination. For spots with irregular contours and inner holes, we found intensity values that were significantly different from those determined by the GenePix Pro microarray analysis software. We determined the set of differentially expressed genes from our intensities and identified more activated genes than were predicted by the GenePix software.
Conclusions: Our method represents a worthwhile alternative and complement to standard approaches used in industry and academy. We highlight the importance of our spot segmentation approach, which identified supplementary important genes, to better explains the molecular mechanisms that are activated in a defense responses to virus and pathogen infection.
BACKGROUND AND PURPOSE: We evaluated cerebral white and gray matter changes in patients with iRLS in order to shed light on the pathophysiology of this disease.
METHODS: Twelve patients with iRLS were compared to 12 age- and sex-matched controls using whole-head diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) techniques. Evaluation of the DTI scans included the voxelwise analysis of the fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD).
RESULTS: Diffusion tensor imaging revealed areas of altered FA in subcortical white matter bilaterally, mainly in temporal regions as well as in the right internal capsule, the pons, and the right cerebellum. These changes overlapped with changes in RD. Voxel-based morphometry did not reveal any gray matter alterations.
CONCLUSIONS: We showed altered diffusion properties in several white matter regions in patients with iRLS. White matter changes could mainly be attributed to changes in RD, a parameter thought to reflect altered myelination. Areas with altered white matter microstructure included areas in the internal capsule which include the corticospinal tract to the lower limbs, thereby supporting studies that suggest changes in sensorimotor pathways associated with RLS.
Resistance in glucocorticoid-induced apoptosis is associated with poor prognosis for long term survival in childhood acute lymphoblastic leukemia (ALL). As Smac mimetics have been shown to reactivate apoptosis by antagonizing Inhibitor of Apoptosis (IAP) proteins, we investigate the potential of the Smac mimetic BV6 to overcome glucocorticoid-resistance in ALL. This study shows that BV6 synergistically cooperates with glucocorticoids to trigger apoptosis and to suppress clonogenic growth of pediatric ALL cells. Of note, the BV6/glucocorticoid combination treatment also induces cell death in cells having defects in the apoptotic signaling cascade by inducing a switch from apoptotic to necroptotic cell death. The clinical relevance of our novel combination treatment is underscored by parallel experiments in primary pediatric ALL samples, in which glucocorticoids and BV6 act together to induce cell death in a synergistic manner. Importantly, the addition of BV6 enhances the anti-leukemic effects of glucocorticoids in an in vivo mouse model of pediatric ALL without causing substantial side effects, highlighting the potency of a BV6/glucocorticoid combination treatment. In contrast, BV6 does not increase cytotoxicity of glucocorticoids against several non-malignant cell types of the lympho-hematopoietic system. Furthermore, we have identified the novel underlying mechanism of BV6/glucocorticoid-induced apoptosis by showing that BV6 and glucocorticoids synergistically act together to promote assembly of the ripoptosome, a RIP1/FADD/caspase-8-containing cell death complex. Ripoptosome assembly is critically required for BV6/Dexamethasone-induced cell death, since genetic silencing of its members, i.e. RIP1, reduces ROS production, caspase activation and most importantly cell death induction. BV6/glucocorticoid combination treatment promotes ripoptosome assembly by inhibition of both of its negative regulators, IAP proteins and cFLIP. Thus, we identify that BV6 and glucocorticoids cooperate together to reduce cIAP1, cIAP2 and XIAP protein levels and cFLIP expression. Ripoptosome formation occurs independently of autocrine/paracrine loops of death receptor ligands, since blocking antibodies for TNFα, TRAIL or CD95L or genetic silencing of their corresponding receptors fail to rescue BV6/glucocorticoid-induced cell death. In summary, this study shows that the Smac mimetic BV6 sensitizes for glucocorticoid-induced apoptosis by promoting ripoptosome assembly with important implications for the treatment of childhood ALL.
In Südtirol wurde 2014 erstmals ein landesweiter Fahrradwettbewerb organisiert, der die Südtiroler Bevölkerung auf spielerische Weise davon überzeugen sollte, für Alltagswege auf das Fahrrad umzusteigen. Die 1.219 Teilnehmenden am Wettbewerb sind insgesamt mehr als 850.000 Kilometer geradelt. Diese Evaluation soll zeigen, ob der Fahrradwettbewerb eine erfolgreiche Maßnahme war, um den Radverkehr in Südtirol zu fördern, also ob tatsächlich eine Verlagerung vom motorisierten Individualverkehr auf den Radverkehr erreicht wurde. Der Erfolg ähnlicher Wettbewerbe wurde bislang vor allem in den Teilnehmer- und Kilometerzahlen gemessen, eine wissenschaftliche Evaluation der durch die Kampagnen erreichten (Verlagerungs-)Effekte fand bislang kaum statt. Die Evaluation des Südtiroler Fahrradwettbewerbs orientiert sich am MaxSumo-Leitfaden zur Evaluation von Mobilitätsmanagementmaßnahmen. Zusätzlich wurden die Motive und Wünsche der Teilnehmenden und Veranstalter herausgearbeitet und der Südtiroler Fahrradwettbewerb mit anderen Fahrradwettbewerben verglichen.
We analysed our experimental recent findings of the dipole response of the odd-mass stable nucleus 205Tl within the quasi-particle phonon model. Using the phonon basis constructed for the neighbouring 204Hg and wave function configurations for 205Tl consisting of a mixture of quasiparticle ⊗ N-phonon configurations (N=0,1,2), only one group of fragmented dipole excited states has been reproduced at 5.5 MeV in comparison to the experimental distribution which shows a second group at about 5 MeV. The computed dipole transition strengths are mainly of E1 character which could be associated to the pygmy dipole resonance.
Die Zahl der Verfahren und der Sterilisationen nach dem Gesetz zur Verhütung erbkranken Nachwuchses
(2015)
In dem Buch wird die Zahl der Verfahren nach dem Gesetz zur Verhütung erbkranken Nachwuchses von 1934 bis 1945 (nach Hochrechnung) im "Altreich" auf ca. 436.000 geschätzt. Durchgeführt wurden laut Schätzung im "Altreich" ca. 294.000 Sterilisationen. Dazu kommen noch ca. 10.000 bis 20.000 Sterilisationen in den "angeschlossenen" oder annektierten Gebieten bis 1945.
Die diesjährige DVPW-Tagung Ende September sorgte für einige Unruhen in den Reihen der Vereinigung und darüber hinaus. Dabei geriet die eigentliche Tagung zum Thema „Vorsicht Sicherheit. Legitimationsprobleme der Ordnung von Sicherheit“ durch die Querelen auf der Mitgliederversammlung fast völlig aus dem Blick. Einen guten und umfassenden Tagungsbericht, um die inhaltliche Debatte nicht gänzlich in Vergessenheit geraten zu lassen, stellten die Kollegen des Theorieblogs zusammen (siehe hier ), live bloggten die Kollegen des Sicherheitsblogs (siehe hier)...
Persons traveling to participate in foreign conflicts by no means constitute a new phenomenon that is intrinsically tied to the ‘Islamic State’ (‘IS’). However, law enforcement agencies all over the world increasingly focus on foreign fighters travelling to Syria and Iraq due to a considerable rise in their number as well as the perceived threat they pose upon their return. Currently, around 650 German residents and citizens have travelled to the region to support jihadist groups such as the ‘IS’.
Low interest rates are becoming a threat to the stability of the life insurance industry, especially in countries such as Germany, where products with relatively high guaranteed returns sold in the past still represent a prominent share of the total portfolio. This contribution aims to assess and quantify the effects of the current low interest rate phase on the balance sheet of a representative German life insurer, given the current asset allocation and the outstanding liabilities. To do so, we generate a stochastic term structure of interest rates as well as stock market returns to simulate investment returns of a stylized life insurance business portfolio in a multi-period setting. Based on empirically calibrated parameters, we can observe the evolution of the life insurers’ balance sheet over time with a special focus on their solvency situation. To account for different scenarios and in order to check the robustness of our findings, we calibrate different capital market settings and different initial situations of capital endowment. Our results suggest that a prolonged period of low interest rates would markedly affect the solvency situation of life insurers, leading to a relatively high cumulative probability of default, especially for less capitalized companies. In addition, the new reform of the German life insurance regulation has a beneficial effect on the cumulative probability of default, as a direct consequence of the reduction of the payouts to policyholders.
This paper investigates systemic risk in the insurance industry. We first analyze the systemic contribution of the insurance industry vis-à-vis other industries by applying 3 measures, namely the linear Granger causality test, conditional value at risk and marginal expected shortfall, on 3 groups, namely banks, insurers and non-financial companies listed in Europe over the last 14 years. We then analyze the determinants of the systemic risk contribution within the insurance industry by using balance sheet level data in a broader sample. Our evidence suggests that i) the insurance industry shows a persistent systemic relevance over time and plays a subordinate role in causing systemic risk compared to banks, and that ii) within the industry, those insurers which engage more in non-insurance-related activities tend to pose more systemic risk. In addition, we are among the first to provide empirical evidence on the role of diversification as potential determinant of systemic risk in the insurance industry. Finally, we confirm that size is also a significant driver of systemic risk, whereas price-to-book ratio and leverage display counterintuitive results.
This paper investigates systemic risk in the insurance industry. We first analyze the systemic contribution of the insurance industry vis-à-vis other industries by applying 3 measures, namely the linear Granger causality test, conditional value at risk and marginal expected shortfall, on 3 groups, namely banks, insurers and non-financial companies listed in Europe over the last 14 years. We then analyze the determinants of the systemic risk contribution within the insurance industry by using balance sheet level data in a broader sample. Our evidence suggests that i) the insurance industry shows a persistent systemic relevance over time and plays a subordinate role in causing systemic risk compared to banks, and that ii) within the industry, those insurers which engage more in non-insurance-related activities tend to pose more systemic risk. In addition, we are among the first to provide empirical evidence on the role of diversification as potential determinant of systemic risk in the insurance industry. Finally, we confirm that size is also a significant driver of systemic risk, whereas price-to-book ratio and leverage display counterintuitive results.
This article intends to give an overview about developments in European Regulatory and Health Technology Assessment (HTA) of new cancer drugs. As background information, it will refer to an overview article by Bergmann et al. [1], which pointed out the status and the limitations of the current system. The authors discussed possible steps to improve the interface between regulators and HTA bodies but stated that this alone will not be sufficient to overcome heterogeneous HTA assessments between HTA agencies. Major issues and challenges for the foreseeable future will be to overcome the heterogeneity of patient access decisions of pharmaceutical payers across Europe which is due to (i) considerably different scientific approaches and methodology to the more or less formal evaluation of cost-effectiveness; (ii) differing health priorities across the countries that reflect historically developed cultural differences and values or different unmet medical needs and (iii) different economic strengths among nations, regions and locales that necessarily drive health care budgetary decisions. The authors consider that this needs a science-based common position on methodology, greater commitments by politicians and health care decision makers to ensure equal access for patients across the EU to anti-tumour medicines. ...
Klimaschutz- und Anpassungsmaßnahmen : Zielkonflikte und Synergien mit dem Biodiversitätsschutz
(2015)
Der Klimawandel ist eine der größten Herausforderungen der Gegenwart und seine Auswirkungen auf Natur, Gesellschaft und Wirtschaft werden vielfach untersucht. Minderungs- wie auch Anpassungsmaßnahmen sind somit ein wichtiges Handlungsfeld geworden. Während der Einfluss des Klimawandels auf die Biodiversität bereits seit Längerem Gegenstand wissenschaftlicher Untersuchungen ist, rücken nun auch mögliche Folgen von Klimaschutz- und Anpassungsmaßnahmen auf die biologische Vielfalt in den Fokus der Forschung: So ist eine generelle Treibhausgasreduktion zwar prinzipiell förderlich, jedoch kann die Umsetzung der hierfür notwendigen Maßnahmen zu Zielkonflikten mit dem Biodiversitätsschutz führen. Gleichwohl gibt es Herangehensweisen, die Synergien beider Bereiche erkennen lassen.
Das Papier bietet einen Überblick über Maßnahmen des Klimaschutzes und der Klimawandelanpassung in den Bereichen Wald- und Forstwirtschaft, Moore, Landwirtschaft, nachwachsende Rohstoffe, Fließgewässer, Küsten und Meere. Diese werden mit Blick auf ihre möglichen (sowohl förderlichen als auch abträglichen) Auswirkungen auf die Biodiversität vorgestellt. Mit dieser problemorientierten Diskursfeldanalyse soll ein Beitrag geleistet werden, potentielle Zielkonflikte von Klima- und Biodiversitätsschutz zu erkennen und Synergien zu fördern.
Aging of biological systems is accompanied by degeneration of mitochondrial functions. Different pathways are active to counteract the processes which lead to mitochondrial dysfunction. Mitochondrial dynamics, the fission and fusion of mitochondria, is one of these quality control pathways. Mitophagy, the controlled degradation of mitochondria, is another one. Here we show that these pathways are linked. A double deletion mutant of Saccharomyces cerevisiae in which two essential components of the fission and fusion machinery, Dnm1 and Mgm1, are simultaneously ablated, contain wild-type like filamentous mitochondria, but are characterized by impaired respiration, an increased sensitivity to different stressors, increased mitochondrial protein carbonylation, and a decrease in mitophagy and replicative lifespan. These data show that a balanced mitochondrial dynamics and not a filamentous mitochondrial morphotype per se is the key for a long lifespan and demonstrate a cross-talk between two different mitochondrial quality control pathways.
Orientation: Employees’ perceptions of their leaders’ behaviour play a role in creating empowering environments where employees are willing to do more than what is expected, with retention of employees as a result. Research purpose: The aim of this study was to theoretically conceptualise and empirically determine the relationships between employees’ perception of their leaders’ empowering behaviour, psychological empowerment, organisational citizenship behaviours and intention to leave within a manufacturing division of an organisation. Motivation for the study: In the ever-changing work environment, organisations must capitalise on their human capital in order to maintain competitiveness. It is therefore important to identify the role of employees’ perception of leadership in contributing to the establishment of an environment where employees feel empowered, are willing to do more than what is expected and want to stay in the organisation. Research design, approach and method: A non-experimental, cross-sectional survey design was used. The total population (N = 300) employed at the manufacturing division was targeted. Two hundred completed questionnaires were obtained. The Leader Empowering Behaviour Questionnaire, Measuring Empowerment Questionnaire, Organisational Citizenship Behaviour Questionnaire and Intention to Leave Scale were administered. Main findings: Employees’ perception of their leaders’ empowering behaviour (keeping employees accountable, self-directed decision-making and people development), psychological empowerment (attitude and influence) and organisational citizenship behaviours (loyalty, deviant behaviour and participation) predict intention to leave the organisation. Practical/managerial implications: Organisations should foster the elements of a positive organisation, in this case leader empowering behaviours, if they want to retain their employees. Contribution/value-add: The results of this research contribute to scientific knowledge about the positive effects of employees experiencing their leaders as empowering.
This is the first article in our series on refugees.Attempts to address the current crisis often seek to make distinctions between ‘refugees’ and ‘migrants’ and between refugees / migrants and citizens. But, I suggest, these distinctions are part of the problem. Part of the solution is to rethink our histories of ‘national states’ – and the rights and claims they enable – through a ‘connected sociologies’ approach that acknowledges the shared histories that bring states and colonies together....
Ataxia telangiectasia (A-T) is a rare, progressive, multisystem disease that has a large number of complex and diverse manifestations which vary with age. Patients with A-T die prematurely with the leading causes of death being respiratory diseases and cancer. Respiratory manifestations include immune dysfunction leading to recurrent upper and lower respiratory infections; aspiration resulting from dysfunctional swallowing due to neurodegenerative deficits; inefficient cough; and interstitial lung disease/pulmonary fibrosis. Malnutrition is a significant comorbidity. The increased radiosensitivity and increased risk of cancer should be borne in mind when requesting radiological investigations. Aggressive proactive monitoring and treatment of these various aspects of lung disease under multidisciplinary expertise in the experience of national multidisciplinary clinics internationally forms the basis of this statement on the management of lung disease in A-T. Neurological management is outwith the scope of this document.
The mammalian family of bears (Ursidae) comprises eight extant species, occurring on four different continents. Among them are the iconic and well-known brown and polar bears, both widely distributed across the Northern hemisphere. Their intraspecific genetic structuring has been extensively investigated, albeit with a focus on genetic markers from maternally inherited parts of their genomes (mitochondrial DNA). The evolutionary relationship and divergence time between brown and polar bears have recently triggered an extensive debate, while less focus has been put on to other parts of the ursid phylogeny, particularly to a clade of three Asian bear species. To date, whole genomes of more than 100 bear individuals from four different species have been sequenced. Yet, one fundamental part of the genome has been largely omitted from specific analyses, in bears as well as in most other mammals: the Y chromosome.
The mammalian Y chromosome provides a unique perspective on the evolutionary history of organisms due to its distinct features, and specifically reflects the patriline because of its male-specific inheritance. The characteristics of this chromosome make it well suited to complement and contrast evolutionary inferences based on other genetic markers, and to uncover processes like sex-biased gene flow and hybridization. The unique insights that can be gained from analyses of Y-linked genetic variation made me utilize this part of the genome to investigate the evolution of male lineages in bears. Studying the patriline is particularly promising in this taxonomic group because of male-biased dispersal and a complex and fast radiation of bears. The analysis of Y-chromosomal genetic markers is thus the common theme of this dissertation: I present the identification of large amounts of Y-chromosomal sequence, the development of male-specific markers from such sequences, and the application of these markers to trace the evolution of male lineages of different bear species.
Specifically, I developed a molecular sex determination system based on the detection of two Y-linked fragments that allows to reliably discriminate between females and males from seven different bear species (Bidon et al. 2013). The approach is highly sensitive, bear-specific, and can be applied in standard molecular laboratories. This makes it valuable in conservation genetics and forensic applications, e.g. to analyze non-invasively collected samples.
Furthermore, I used Y-linked markers in a comprehensive and range-wide sample of brown and polar bears, and show that male-biased gene flow plays an important role in distributing genetic material throughout the ranges of both species (Bidon et al. 2014). In brown bears, I detected a lack of paternal population structuring which is in strong contrast to the detailed structuring of the matriline.
Analyzing Y-chromosomal sequences from all eight bear species, I present a phylogeny of the patriline that largely resembles the topology from other nuclear markers but is different from the topology of the mitochondrial gene tree (Kutschera et al. 2014). This discordance among loci generates interesting hypotheses about inter-species gene flow, particularly among American and Asiatic black bears.
With the identification of almost two million basepairs of Y-chromosomal sequence and the analysis of an unprecedented large male-specific dataset in polar bears, a high-resolution view on the distribution of their intraspecific variation was obtained (Bidon et al. 2015). In particular, two clades that are divergent but do not show pronounced phylogeographic structure were detected, confirming the great dispersal capacity of males of this high arctic species.
This dissertation thus represents a comprehensive investigation of Y-linked genetic variation on the intra- and interspecific level in a non-model organism. With my research, I contribute to an increased understanding of the complex evolutionary history of bears. In particular, I show that male-biased gene flow strongly influences the distribution of nuclear genetic variation, and that the contrast between phylogenies of differentially inherited markers can help to understand interspecific hybridization between closely related species. Moreover, my findings demonstrate the potential of Y-chromosomal markers to uncover unknown evolutionary patterns and processes. This applies not only to bears but to many species, even such that are generally well known and well described.
Dies ist der vierte Artikel unseres Blogfokus „Salafismus in Deutschland“.
Worüber sprechen wir eigentlich, wenn wir über Salafismus sprechen? Obgleich oder gerade weil der Begriff in aller Munde ist, werden mitunter unterschiedliche Dinge als salafistisch (wahlweise auch als wahhabitisch, islamistisch, dschihadistisch) bezeichnet, spezifische Dimensionen des Phänomens als Wesen „des“ Salafismus behauptet oder gleich ganz auf eine begriffliche Bestimmung verzichtet. Dies ist problematisch, da es zu einem besseren Verständnis des Phänomens der Verständigung über dessen Bedeutung(en) bedarf. Sonst besteht die Gefahr des aneinander Vorbeiredens. Des Weiteren machen Worte Politik. Eine unscharfe Etikettierung kann fragwürdigen Politiken und einer Stigmatisierung Vorschub leisten und negative nicht-intendierte Konsequenzen haben....
Nach dem Ausfall der vergangenen Woche, gibt es diese Woche wieder eine Netzschau. Alles beim Alten, bin ich geneigt zu sagen. Aber das stimmt nicht ganz. Diese Ausgabe ist eine Übergangs-Netzschau und kommt deshalb sehr schlank daher. Wir überlegen, das Format drastisch zu verändern. Über das “wie” ist bisher allerdings noch keine Entscheidung gefallen. Wer uns Tipps geben mag, wie ihre/seine perfekte Netzschau aussehen würde oder was wir auf jeden Fall verändern sollten, kommentiere bitte diesen Beitrag. Danke!
Beste! Neues in der Blogroll
(2015)
Hin und wieder muss einfach mal ordentlich entrümpelt und aufgeräumt werden. Das gilt für das Leben im Allgemeinen und hin und wieder eben auch für das Bretterblog. Heute war es mal wieder soweit. Hoch motiviert von den verwegenen Plänen des letzten Redaktionstreffens habe ich mich unter anderem an unsere Blogroll gewagt: Einmal durchgeklickt, Blogleichen weggeräumt und gestaunt, was für starke Blogs es doch so da draußen gibt, die man hin und wieder mal aus dem Auge verliert!...
Das Ziel des heute startenden Blogforums ist es in den nächsten Wochen in gut verdaubaren Beiträgen blinde Flecken zu beleuchten, bereits bekannte Aspekte zu vertiefen, vermeintliche Gewissheiten aufzubrechen und so den Diskurs über „IS“ konstruktiv zu prägen. Dieser Aufgabe haben sich mehr als zwei Dutzend Expertinnen und Experten aus Wissenschaft, öffentlichen und privaten Sicherheitsinstitutionen, Journalismus, Entwicklungszusammenarbeit und De-Radikalisierungspraxis verschrieben...
Vorbemerkung des Autors: Dieser Artikel wurde bereits am 26. Januar im Sicherheitspolitik-Blog veröffentlicht. Es handelt sich um den Auftaktbeitrag eines Blogforums zum “Islamischen Staat”, das von dem Autor dieses Beitrags organisiert wurde (siehe bspw. ein Beitrag zu Belgien als Brutstätte von IS-Kämpfern: http://goo.gl/QWgEip). Das Bretterblog übernimmt ausgewählte Beiträge.
In der Netzschau dieser Woche geht es um afghanischen Aktivismus für Frauenrechte, Joseph Blatters opportunistische Thematisierung von Diskriminierung von Frauen im Iran, die Wirksamkeit von Mikrokrediten, den Islamischen Staat und die Probleme des Nahen und Mittleren Ostens und die Überwachung durch die NSA.
Dies ist der erste Artikel unseres Blogfokus „Salafismus in Deutschland“.
„Der Salafismus“ oder „die Salafisten“ sind seit wenigen Jahren in aller Munde. Obgleich oftmals nicht klar ist, was oder wer auf diese Weise bezeichnet wird, dient das Label zunehmend als Projektionsfläche für sicherheits- und gesellschaftspolitische Ängste vor „islamistischem Terrorismus“ und der Verbreitung von anti-demokratischem und anti-emanzipatorischen Gedankengut. Begrifflich löst „Salafismus“ im öffentlichen Diskurs den zuvor gebräuchlicheren (aber etwas anders gelagerten) Terminus des „Islamismus“ ab und rückt in die Nähe von Extremismus, Gewalt und Terrorismus. Obgleich die salafistische Ideologie und Bewegung in den genannten Hinsichten als problematisch angesehen werden können, ist diese Begriffsverwendung für die Analyse und den Umgang mit dem Phänomen umstritten: Sie kann sowohl das Verständnis des Phänomens als auch die Handlungsoptionen staatlicher und zivilgesellschaftlicher Akteure verengen....
In diesem Beitrag werden die Angaben aus der Beschäftigtenbefragung der GDA-Dachevaluation zum Thema Belastungen am Arbeitsplatz unter verschiedenen Aspekten ausgewertet. Insbesondere erfolgt eine Betrachtung der hessischen Daten, die den Ergebnissen der Gesamtstichprobe gegenübergestellt werden; weiterhin wird eine nach Branchen und Betriebsgrößen differenzierte Betrachtung dargestellt. Außerdem wird in bi- und multivariaten Modellen untersucht, welche Faktoren einen Einfluss auf die Belastungswahrnehmung haben.
In einem weiteren Schritt werden die Einschätzungen der Beschäftigten den Ergebnissen der Betriebsbefragung gegenübergestellt, um Unterschiede bzw. Ähnlichkeiten dieser beiden Gruppen hinsichtlich der Wahrnehmung der betrieblichen Situation zu betrachten.
Als wichtiges Ergebnis hat sich gezeigt, dass für die Beschäftigten die „Arbeit unter Zeitdruck“ den wesentlichen Belastungsfaktor darstellt. Neben diesem psychischen Belastungsfaktor spielen aber auch physisch-technische Belastungsfaktoren, d.h. schwere körperliche Arbeit und Umgebungsfaktoren, nach wie vor eine große Rolle. Erwartungsgemäß gibt es große Unterschiede hinsichtlich der wahrgenommenen Belastungen zwischen den Wirtschaftssektoren. In Hessen spielen Belastungen durch bewegungsarme Tätigkeiten eine deutlich größere Rolle als im Schnitt aller Länder.
Die Ergebnisse aus einer bi- beziehungsweise multivariaten Auswertung der Daten zeigen, dass neben der Branche auch die betrieblichen Arbeitsschutzaktivitäten einen nachweisbaren Einfluss auf die Belastungswahrnehmung der Beschäftigten haben. Weiterhin wird deutlich, dass die Beschäftigten in der Wahrnehmung der Belastung eine klare Unterscheidung zwischen physisch-technischen Belastungen und psychischen Faktoren treffen. Belastungen aus bewegungsarmen Tätigkeiten spielen insgesamt eine große Rolle, lassen sich aber eindeutig keinem dieser Belastungskomplexe zuordnen.
Aus der Gegenüberstellung der Befunde der Beschäftigtenbefragung mit den Ergebnissen der Befragung der Betriebe ergibt sich, dass Führungskräfte bzw. Expert/innen die betrieblichen Belastungskonstellationen anders wahrnehmen als die Beschäftigten: die Beschäftigten nehmen psychische Belastungen an einem deutlich höheren Anteil der Arbeitsplätze wahr, wohingegen die betrieblichen Vertreter/innen Belastungen nach wie vor eher im technischen Bereich sehen.
During the last decade, Bayesian probability theory has emerged as a framework in cognitive science and neuroscience for describing perception, reasoning and learning of mammals. However, our understanding of how probabilistic computations could be organized in the brain, and how the observed connectivity structure of cortical microcircuits supports these calculations, is rudimentary at best. In this study, we investigate statistical inference and self-organized learning in a spatially extended spiking network model, that accommodates both local competitive and large-scale associative aspects of neural information processing, under a unified Bayesian account. Specifically, we show how the spiking dynamics of a recurrent network with lateral excitation and local inhibition in response to distributed spiking input, can be understood as sampling from a variational posterior distribution of a well-defined implicit probabilistic model. This interpretation further permits a rigorous analytical treatment of experience-dependent plasticity on the network level. Using machine learning theory, we derive update rules for neuron and synapse parameters which equate with Hebbian synaptic and homeostatic intrinsic plasticity rules in a neural implementation. In computer simulations, we demonstrate that the interplay of these plasticity rules leads to the emergence of probabilistic local experts that form distributed assemblies of similarly tuned cells communicating through lateral excitatory connections. The resulting sparse distributed spike code of a well-adapted network carries compressed information on salient input features combined with prior experience on correlations among them. Our theory predicts that the emergence of such efficient representations benefits from network architectures in which the range of local inhibition matches the spatial extent of pyramidal cells that share common afferent input.
In the aftermath of the global financial crisis, both resolution planning, i.e. contingency planning by both regulated institutions and public authorities in order to prepare their actions in financial crisis, and concepts for structural bank reform have been identified as possible solutions to ending “Too Big To Fail” and foster market discipline among bank owners, bank managers and investors in bank debt. Both concepts thus complement the global quest for reliable procedures and tools for bank resolution that would minimise systemic implications once large and complex financial institutions have reached the stage of insolvency. Given the complex task of orchestrating swift and effective resolution actions, especially with regard to cross-border banking groups and financial conglomerates, planning ahead in good times has since been widely recognised as crucial for enhancing resolvability. At least part of the impediments to resolution will be found in organisational, financial and legal complexity that has evolved in banks and groups over time. To remove these impediments, interference with existing corporate and group structures is all but inevitable. However, in both international standard setting and at the European Union level, issues related to resolution planning (within the context of bank resolution reform) and structural banking reforms to date have been discussed rather separately. This lack of consistency is questionable, given the obvious need to reconcile both approaches in order to facilitate effective implementation and enforcement especially with regard to large, complex banking groups. Based on an analysis both of the Bank Recovery and Resolution Directive and the SRM Regulation, this paper explores how these problems could be dealt with within the context of the European Banking Union.
The creation of the Banking Union is likely to come with substantial implications for the governance of Eurozone banks. The European Central Bank, in its capacity as supervisory authority for systemically important banks, as well as the Single Resolution Board, under the EU Regulations establishing the Single Supervisory Mechanism and the Single Resolution Mechanism, have been provided with a broad mandate and corresponding powers that allow for far-reaching interference with the relevant institutions’ organisational and business decisions. Starting with an overview of the relevant powers, the present paper explores how these could – and should – be exercised against the backdrop of the fundamental policy objectives of the Banking Union. The relevant aspects directly relate to a fundamental question associated with the reallocation of the supervisory landscape, namely: Will the centralisation of supervisory powers, over time, also lead to the streamlining of business models, corporate and group structures of banks across the Eurozone?
Introduction: Organ dysfunction or failure after the first days of ICU treatment and subsequent mortality with respect to the type of intensive care unit (ICU) admission is poorly elucidated. Therefore we analyzed the association of ICU mortality and admission for medical (M), scheduled surgery (ScS) or unscheduled surgery (US) patients mirrored by the occurrence of organ dysfunction/failure (OD/OF) after the first 72h of ICU stay.
Methods: For this retrospective cohort study (23,795 patients; DIVI registry; German Interdisciplinary Association for Intensive Care Medicine (DIVI)) organ dysfunction or failure were derived from the Sequential Organ Failure Assessment (SOFA) score (excluding the Glasgow Coma Scale). SOFA scores were collected on admission to ICU and 72h later. For patients with a length of stay of at least five days, a multivariate analysis was performed for individual OD/OF on day three.
Results: M patients had the lowest prevalence of cardiovascular failure (M 31%; ScS 35%; US 38%), and the highest prevalence of respiratory (M 24%; ScS 13%; US 17%) and renal failure (M 10%; ScS 6%; US 7%). Risk of death was highest for M- and ScS-patients in those with respiratory failure (OR; M 2.4; ScS 2.4; US 1.4) and for surgical patients with renal failure (OR; M 1.7; ScS 2.7; US 2.4).
Conclusion: The dynamic evolution of OD/OF within 72h after ICU admission and mortality differed between patients depending on their types of admission. This has to be considered to exclude a systematic bias during multi-center trials.
Die vorliegende Arbeit verfolgt den Anspruch, die von Paul Natorp (1907) gestellte Frage, was die Gemeinschaft für die Erziehung und umgekehrt die Erziehung für die Gemeinschaft bedeute, empirisch auszuloten. Im Mittelpunkt des Forschungsinteresses steht dabei das Verhältnis von Schule und Gemeinschaft in der ‚postnationalen Konstellation‘ (Habermas 1998), dem sich die Arbeit über die Untersuchung von Unterrichtskommunikation zu den Themen ‚Nationalsozialismus/Holocaust‘ und ‚Multikulturalismus/Rassismus‘ anzunähern versucht.
Zur Vorbereitung der empirischen Studie wird im Rahmen einer Semantikstudie zunächst der pädagogische Diskurs zum Thema Gemeinschaft von den ersten Vorläufern gemeinschaftspä-dagogischen Denkens bis hin zu aktuellen konzeptionellen Entwürfen nachgezeichnet. Funktion und Bedeutung der Gemeinschaftsfigur als Bezugskategorie von Erziehungsreflexion in der Moderne werden herausgearbeitet. Weiterhin werden die rekonstruierten gemeinschaftspädagogischen Konzepte in Hinblick auf ihr Spannungspotential zu Leitprinzipien demokratischer Erziehung beleuchtet.
Mithilfe sequenzanalytischer Interpretationen wird anschließend der Frage nachgegangen, welche Rolle Gemeinschaftsbezügen als Fluchtpunkt pädagogischer Einwirkungsbemühungen im Unterricht zukommt. Gleichzeitig wird gefragt, ob und in welcher Weise Unterricht Gemeinschaft als Ermöglichungsform zur Umsetzung seiner pädagogischen Absichten in Anspruch nimmt. Nicht zuletzt richtet die Analyse das Augenmerk auf den Umgang mit den potentiellen Herausforderungen, die unter Migrationsbedingungen mit dem Rekurrieren auf Gemeinschaft am Lernort (Geschichts-)Unterricht verbunden sind.
Die Interpretationen zeigen, wie Unterricht Gemeinschaft in Anspruch nimmt, um die Bedingungen seines Prozessierens zu sichern. Weiterhin decken sie zwei kontrastierende Typen des Rekurrierens auf Gemeinschaft als Fluchtpunkt pädagogischer Kommunikation zum Thema NS auf. Als Lösungsoption im Umgang mit den migrationsbedingten Herausforderungen von Geschichtsunterricht zum Thema NS deutet sich indes die Tendenz an, verstärkt auf eine universalistische Erinnerungs- und Verantwortungskultur Bezug zu nehmen.
Das Gefahrenpotential, das dem Gemeinschaftsgedanken in der aktuellen erziehungswissenschaftlichen Diskussion zugeschrieben wird, erweist sich in den betrachteten Unterrichtsse-quenzen als beschränkt. Die Beobachtungen legen vielmehr die These einer eingehegten Form von Gemeinschaftserziehung in der gegenwärtigen Unterrichtspraxis nahe. Darin erfährt das Risiko, das gemeinschaftspädagogischen Ansätzen ihrer Kritik nach eingeschrieben ist, über normative Selbstverpflichtungen der pädagogischen Praxis eine Eindämmung.
BANK INSTABILITY SEEMINGLY COULD PUSH BORROWERS TO USE CROWDFUNDING AS A SOURCE OF EXTERNAL FINANCE. WE CONSTRUCT A NOVEL, HAND-COLLECTED DATA SET OF VENTURES' USES OF EQUITY CROWDFUNDING IN GERMANY, THEIR RELATIONSHIPS WITH BANKS, AND VARIOUS VENTURE TRAITS SINCE 2011. BY OBSERVING VENTUREBANK RELATIONSHIPS, WE CAN IDENTIFY IF VENTURES CONNECTED TO SHOCKED BANKS ARE MORE LIKELY TO USE CROWDFUNDING IN AN ATTEMPT TO SUBSTITUTE FOR CONTRACTING BANK CREDIT SUPPLY. OUR RESULTS SHOW THAT CROWDFUNDING IS SIGNIFICANTLY MORE LIKELY FOR NEW VENTURES THAT INTERACT WITH STRESSED BANKS. INNOVATIVE FUNDING SOURCES ARE THUS PARTICULARLY RELEVANT IN TIMES OF STRESS AMONG CONVENTIONAL FINANCIERS. BUT CROWDFUNDED VENTURES ARE GENERALLY ALSO MORE OPAQUE AND RISKY THAN NEW VENTURES THAT DO NOT USE CROWDFUNDING.
Viele Städte in Deutschland stehen aktuell vor komplexen ökonomischen, ökologischen und sozialen Herausforderungen, die mit klassischen ressortbezogenen Planungskonzepten nicht zu bewältigen sind. Integrierte Stadtentwicklungskonzepte erleben deshalb vielerorts eine Renaissance in der städtischen Planungspraxis. Die in diesem Zusammenhang diskutierten Planungsleitbilder geben jedoch nur selten direkt umsetzbare Handlungskonzepte vor. In diesem Beitrag werden deshalb am Beispiel der Stadt Leipzig konkrete Handlungsoptionen für eine an nachhaltiger Mobilität orientierte Stadtentwicklung vorgestellt. Aufbauend auf bisherigen Erkenntnissen zu integrierten Stadtentwicklungskonzepten werden zunächst infrastrukturbezogene Konzepte zur Förderung des Wohnens im Innenbereich, zur Stärkung städtischer Zentren sowie zur Förderung der Nahmobilität dargestellt. Darüber hinaus werden auch politische, organisatorische und kommunikative Handlungsoptionen aufgezeigt. Diese umfassen Maßnahmen zur Verbesserung der übergeordneten Rahmenbedingungen, Konzepte zur Stärkung der inter- und intrakommunalen Kooperation sowie integrierte städtische Mobilitätskonzepte. Das Beispiel Leipzig macht dabei deutlich, dass infrastrukturelle Ansätze für eine an nachhaltiger Mobilitätsgestaltung orientierte Stadtentwicklung nicht ausreichend sind. Vielmehr ist eine bessere Abstimmung der Stadt- und Verkehrsplanung auf die Bedürfnisse der Bevölkerung erforderlich; dazu gehört auch die Integration von Mobilitätsmanagementmaßnahmen in städtische Verkehrskonzepte. Für eine wirksame Umsetzung integrierter Stadtentwicklungskonzepte erscheinen außerdem eine an Nachhaltigkeitszielen orientierte Gestaltung der rechtlichen und politischen Rahmenbedingungen sowie eine stärkere Berücksichtigung regionaler Verknüpfungen in städtischen Planungen notwendig.
Elementar für eine zukunftsfähige Verkehrsplanung ist eine möglichst detaillierte Kenntnis des Mobilitätsverhaltens der Bevölkerung in der Region. Zur Analyse des Mobilitätsverhaltens der Bevölkerung in Deutschland wurden in der Vergangenheit auf verschiedenen räumlichen Ebenen mehrere größtenteils voneinander unabhängige Datenerhebungen durchgeführt. Für die Region Frankfurt Rhein-Main besonders relevant sind dabei zum einen die Längsschnitt- bzw. Panelerhebungen des „Rhein-Main-Panels“ (RMP) und des „Deutschen Mobilitätspanels“ (MOP), zum anderen die Querschnittserhebungen der Befragung „Mobilität in Deutschland“ (MiD) und speziell für Frankfurt auch „Mobilität in Städten – SrV“ (SrV).
Ziel dieser Publikation ist es, diese vier unterschiedlichen Erhebungen in einem kurzen Vergleich vorzustellen. Dabei sollen die jeweiligen spezifischen Potentiale, aber auch Einschränkungen aufgezeigt werden, die diese Mobilitätsdatensätze bezüglich der Auswertung und weiteren Nutzung aufweisen. Danach werden in knapper Form mögliche Kombinationsmöglichkeiten dieser Datensätze untereinander, aber auch mit ergänzenden Datenbeständen dargestellt. Anschließend werden die aus den verschiedenen Mobilitätsdatensätzen ermittelten zentralen regionalen Mobilitätskennziffern in einem Vergleich veranschaulicht. Als Abschluss soll schließlich ein kurzer Blick auf mögliche Anwendungsfelder der Mobilitätsdaten in Politik und Planung geworfen werden.
Salt bridges in lipid bilayers play a decisive role in the dynamic assembly and downstream signaling of the natural killer and T-cell receptors. Here, we describe the identification of an inter-subunit salt bridge in the membrane within yet another key component of the immune system, the peptide-loading complex (PLC). The PLC regulates cell surface presentation of self-antigens and antigenic peptides via molecules of the major histocompatibility complex class I. We demonstrate that a single salt bridge in the membrane between the transporter associated with antigen processing TAP and the MHC I-specific chaperone tapasin is essential for the assembly of the PLC and for efficient MHC I antigen presentation. Molecular modeling and all-atom molecular dynamics simulations suggest an ionic lock-switch mechanism for the binding of TAP to tapasin, in which an unfavorable uncompensated charge in the ER-membrane is prevented through complex formation. Our findings not only deepen the understanding of the interaction network within the PLC, but also provide evidence for a general interaction principle of dynamic multiprotein membrane complexes in immunity.
The interbank market is important for the efficient functioning of the financial system, transmission of monetary policy and therefore ultimately the real economy. In particular, it facilitates banks' liquidity management. This paper aims at extending the literature which views interbank markets as mutual liquidity insurance mechanism by taking into account persistence of liquidity shocks. Following a theory of long-term interbank funding a financial system which is modeled as a micro-founded agent based complex network interacting with a real economic sector is developed. The model features interbank funding as an over-the-counter phenomenon and realistically replicates financial system phenomena of network formation, monetary policy transmission and endogenous money creation. The framework is used to carry out an optimal policy analysis in which the policymaker maximizes real activity via choosing the optimal interest rate in a trade-off between loan supply and financial fragility. It is shown that the interbank market renders the financial system more efficient relative to a setting without mutual insurance against persistent liquidity shocks and therefore plays a crucial role for welfare.
In einer vorangegangenen Studie konnten bereits duale sEH / PPAR-Modulatoren identifiziert werden, welche allerdings nicht in vivo applizierbar waren 73. Der Vorteil des Multi-Target-Liganden Ansatzes konnte demnach nicht evaluiert werden. Das Ziel der folgende Arbeit beschreibt demnach Design, Synthese und Charakterisierung in vivo applizierbarer sEH / PPAR-Modulatoren. Dieser Prozess sollte in drei Phasen gliederte werden:
o Identifizieren einer geeigneten Strukturklasse
o Etablieren einer Struktur-Aktivitäts-Beziehung zu beiden Targets
o Leitstrukturoptimierung
Die gesuchte Zielverbindung sollte nach oraler in vivo Applikation eine ausreichend hohe Plasmakonzentration in vivo erreichen, um konzentrationsabhängig die Targets sEH und PPAR zu modulieren. Mit dieser Modellverbindung wäre es möglich eine vergleichbare Studie zur sEH / PPAR-Kombinationstherapie von Imig et al. 72, durchzuführen. Letztendlich könnte mit dem Vergleich dieser zwei Studien gezeigt werden, ob die simultane Modulation dieser zwei Targets das Potenzial besitzt mehrere Risikofaktoren zu therapieren.
The Asian bush mosquito (Aedes japonicus japonicus, Theobald 1901) is an invasive culicid species which originates in Asia but is nowadays present in northern America and Europe. It is a competent vector for several human disease pathogens. In addition to the public health threat, this invasive species may also be an ecological threat for native container-breeding mosquitoes which share a similar larval habitat. Therefore, it is of importance to gain knowledge on ecological and eco-toxicological features of the Asian bush mosquito. However, optimal laboratory feeding conditions have not yet been established. Standardized feeding methods will be needed in assessing the impact of insecticides or competitional strength of this species. To fill this gap, we performed experiments on food quality and quantity for Ae. j. japonicus larvae. We found out that the commercial fish food TetraMin (Tetra, Melle, Germany) in a dose of 10 mg per larva is the most suitable food tested. We also suggest a protocol with a feeding sequence of seven portions for all larval stages of this species.
Disorder-relevant but task-unrelated stimuli impair cognitive performance in social anxiety disorder (SAD); however, time course and neural correlates of emotional interference are unknown. The present study investigated time course and neural basis of emotional interference in SAD using event-related functional magnetic resonance imaging (fMRI). Patients with SAD and healthy controls performed an emotional stroop task which allowed examining interference effects on the current and the succeeding trial. Reaction time data showed an emotional interference effect in the current trial, but not the succeeding trial, specifically in SAD. FMRI data showed greater activation in the left amygdala, bilateral insula, medial prefrontal cortex (mPFC), dorsal anterior cingulate cortex (ACC), and left opercular part of the inferior frontal gyrus during emotional interference of the current trial in SAD patients. Furthermore, we found a positive correlation between patients’ interference scores and activation in the mPFC, dorsal ACC and left angular/supramarginal gyrus. Taken together, results indicate a network of brain regions comprising amygdala, insula, mPFC, ACC, and areas strongly involved in language processing during the processing of task-unrelated threat in SAD. However, specifically the activation in mPFC, dorsal ACC, and left angular/supramarginal gyrus is associated with the strength of the interference effect, suggesting a cognitive network model of attentional bias in SAD. This probably comprises exceeded allocation of attentional resources to disorder-related information of the presented stimuli and increased self-referential and semantic processing of threat words in SAD.
Dies ist der 13. Artikel unseres Blogfokus zu Flucht und Migration. Kritik an der restriktiven europäischen Migrations- und Flüchtlingspolitik äußert sich nicht nur in Form von rein politischen Initiativen, sondern auch durch zahlreiche Kunstprojekte. Der Beitrag setzt sich anhand des Berliner Zentrums für Politische Schönheit (ZPS) mit kritischer Kunst und Kritik an derselben auseinander. Er plädiert dafür, die Potenziale politischer Kunst dafür anzuerkennen, in der aktuellen Situation politisches Bewusstsein zu stärken und Widerstand sichtbar zu machen.
Stellen wir uns vor, SozialwissenschaftlerInnen würden öfter ihre Komfortzone verlassen und sich in Feldexperimente begeben, anstatt vor Rechnern zu hocken und über ferne Wirklichkeiten zu rätseln und zu urteilen. Der G7-Gipfel im oberbayerischen Elmau bot Leuten, die sich mit (innerer) Sicherheit, Macht und Protest auseinandersetzen dazu eine hervorragende Möglichkeit. Die hier interviewte Politikwissenschaftlerin nahm an den Protesten teil. Da sie aufgrund eines eventuell drohenden Strafverfahrens um ihre eigene Sicherheit fürchtet – die ihres Rufs und ihrer zukünftigen Arbeitsverträge – möchte sie anonym bleiben...
Vielen hängt das Thema „Grexit“ schon zum Hals heraus. Seit dem ersten Hilfspaket 2010 kehrt es wellenartig in der Berichterstattung wieder, seit Wochen ist es das Top-Thema in den deutschen Medien. Ein Abstumpfen gegenüber dem politischen Gerangel sollte aber nicht dazu führen, dass unser kritischer Blick dafür schwindet, wie „Deutschland“ auf die Krise reagiert – sowohl außen- und finanzpolitisch als auch medial...
In-depth analyses of cancer cell proteomes are needed to elucidate oncogenic pathomechanisms, as well as to identify potential drug targets and diagnostic biomarkers. However, methods for quantitative proteomic characterization of patient-derived tumors and in particular their cellular subpopulations are largely lacking. Here we describe an experimental set-up that allows quantitative analysis of proteomes of cancer cell subpopulations derived from either liquid or solid tumors. This is achieved by combining cellular enrichment strategies with quantitative Super-SILAC-based mass spectrometry followed by bioinformatic data analysis. To enrich specific cellular subsets, liquid tumors are first immunophenotyped by flow cytometry followed by FACS-sorting; for solid tumors, laser-capture microdissection is used to purify specific cellular subpopulations. In a second step, proteins are extracted from the purified cells and subsequently combined with a tumor-specific, SILAC-labeled spike-in standard that enables protein quantification. The resulting protein mixture is subjected to either gel electrophoresis or Filter Aided Sample Preparation (FASP) followed by tryptic digestion. Finally, tryptic peptides are analyzed using a hybrid quadrupole-orbitrap mass spectrometer, and the data obtained are processed with bioinformatic software suites including MaxQuant. By means of the workflow presented here, up to 8,000 proteins can be identified and quantified in patient-derived samples, and the resulting protein expression profiles can be compared among patients to identify diagnostic proteomic signatures or potential drug targets.
Das anzuzeigende Buch ist eine Aufsatzsammlung basierend auf einer internationalen Konferenz, die 2011 an der Keio Universität Tokio stattgefunden hat. Von den insgesamt elf Konferenzbeiträgen sind neun in dieser Sammlung vorgelegt. In seiner Einleitung gibt David Sugimoto die Beweggründe für die Wahl des Themas an und erklärt, weshalb die drei Göttinnen im Buchtitel als eine Göttin dargestellt werden, auch wenn er sogleich einräumt, dass noch weitere Göttinnen – Inanna, Isis, Hathor, Tanit und Venus sowie eine nicht näher bestimmte Himmelsgöttin – hätten mit aufgenommen werden können, da auch sie, ebenso wie zahllose lokale Göttinnen der antiken Welt, Aspekte der Ištar, Astarte und Aphrodite besäßen...