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Hintergrund: Den derzeitigen Therapiestandard in der Behandlung des lokal begrenzten Prostatakarzinoms stellen die radikale Prostatektomie und perkutane Radiotherapie dar. Aufgrund der besonderen Strahlenbiologie des PCa (α-/β-Wert 1,5 Gy) ist von einer höheren Sensitivität gegenüber einer Hypofraktionierung auszugehen. Die aktuellen Literaturdaten zeigen eine Nichtunterlegenheit der moderaten Hypofraktionierung gegenüber dem konventionellen Regime, jedoch sind Langzeitergebnisse hinsichtlich der Spättoxizität noch spärlich. In dieser Arbeit werden onkologische Ergebnisse sowie GI-/ und GU-Toxizität nach moderat hypofraktionierter, intensitätsmodulierter (IMRT/VMAT) und bildgeführter (IGRT) Radiotherapie mit simultan integriertem Boost (SIB) in einem universitären Tumorzentrum untersucht.
Patienten und Methoden: In den Jahren 2010 bis 2016 wurden an der Uniklinik Frankfurt 170 Patienten mit histologisch gesichertem lokal begrenzten bis fortgeschrittenen PCa (T1-4, N0-1, M0) mittels moderat hypofraktionierter EBRT in IG-IMRT- bzw. IG-VMAT- und SIB-Technik behandelt. Alle Patienten wurden nach D’Amico-Klassifikation stratifiziert und risikoadaptiert therapiert. Die GI- und GU-Toxizität wurde gemäß CTC v4.0 wöchentlich unter der Therapie und während der Nachbeobachtungszeit erfasst. Ein biochemisches Rezidiv wurde definiert als PSA-Nadir + 2 ng/ml. Die Nachbeobachtung erfolgte 6-8 Wochen, 2-3 Monate und 6 Monate nach Radiotherapie sowie anschließend mindestens einmal jährlich. Die Datenauswertung erfolgte retrospektiv. Für die statistischen Analysen wurden die Software-Programme Excel und SPSS verwendet. Die Kaplan-Meier-Überlebensanalysen wurden mittels Log-Rank-Test verglichen und bei signifikanten Unterschieden in eine Cox-Regression-Analyse aufgenommen. Ein möglicher Zusammenhang zwischen dosimetrischen/klinischen Parametern und GI-/GU-Toxizität wurde mittels Chi-Quadrat-Test nach Pearson geprüft. Für alle durchgeführten Analysen galt ein p-Wert von <0,05 als statistisch signifikant. Ergebnisse: Patienten der low-risk- (n = 15) sowie intermediate- und high-risk-Gruppe mit Z.n. TURP (n= 14) erhielten eine GRD von 73,6 Gy für das PTV1 bzw. 58,24 Gy (PTV2) mit einer Einzeldosis von 2,3 Gy (SIB) bzw. 1,82 Gy in 32 Fraktionen. Patienten der intermediate- (n = 70) und high-risk- (n = 71) Gruppe erhielten eine GRD von 75,9 Gy (PTV1) bzw. 60,06 Gy (PTV2) mit einer Einzeldosis von 2,3 Gy (SIB) bzw. 1,82 Gy in 33 Fraktionen. Eine zusätzliche Bestrahlung des LAG (PTV3) mit einer GRD von 46,0 Gy und 1,84 Gy Einzeldosis in 25 Fraktionen erhielten alle Patienten mit radiologischer cN1-Situation bzw. im Falle eines LK-Befallsrisikos von >20% nach Roach-Formel (n = 86). Eine (neo-) adjuvante AHT erhielten insg. 98 Patienten. Die mediane Nachbeobachtungszeit betrug 36 Monate (Range: 5-84 Monate). Die 24-, 36-, und 60-Monate-ÜLR lagen in der IR-Gruppe bei 98,4%, 96,1% bzw. 89,7% (OS), 98,6% bzw. 94,9% (BC), 97% bzw. 84,5% (DFS) und 98,6% (FFM), in der HR-Gruppe bei 93,1% bzw. 88,8% (OS), 89%, 84,7% bzw. 75,3% (BC), 82,5%, 74,2% bzw. 65,9% (DFS) und 98%, 95,7% bzw. 84,8% (FFM). Weder für die AHT noch die RT des LAG konnte eine Verbesserung des OS, DFS, FFM sowie der BC gezeigt werden. Eine Akuttoxizität Grad 2 trat bei 6,5% (GI) bzw. 16,5% (GU) und Grad 3 bei 0,6% (GI) bzw. 0% (GU) auf. Eine Spättoxizität Grad 2 trat bei 2,9% (GI) bzw. 12,4% (GU) und Grad 3 bei 0,6% (GI) bzw. 1,2% (GU) auf.
Schlussfolgerung: Mit Implementierung der moderat hypofraktionierten EBRT nach o.g. Schema (73,6 Gy (79,9 Gy nach EQD2 (αβ 1,5)) bzw. 75,9 Gy (82,4 Gy nach EQD2 (αβ 1,5)) konnten im Rahmen dieser retrospektiven Kohortenstudie sehr gute Ergebnisse für intermediate- und high risk-Patienten des lokal begrenzten bis fortgeschrittenen PCa hinsichtlich der onkologischen Endpunkte sowie der GI-/GU-Toxizität, vergleichbar mit den besten Ergebnissen aktueller Publikationen, erzielt werden. Diese Ergebnisse bekräftigen die zunehmende Anwendung dieser Bestrahlungstechnik. Die Kohorte sollte zur Validierung der Ergebnisse weiter expandiert und mit einer längeren Nachbeobachtungszeit erneut ausgewertet werden.
This Policy Letter outlines a pandemic insurance solution through a pandemic-related “Insurance Linked Bond”. It would be originated by governments, with a principal amount to cover significant costs resulting from a pandemic. These bonds, which would be traded on a secondary market, generate a risk-adequate return for private and institutional investors that is financed through the insurance premiums paid by the public domain. In case of a pre-defined pandemic trigger event, the principal of the bond becomes available for the originating governments to cover pandemic-related costs. Through this approach, governments can insure themselves against future pandemic-related risks, while funding comes primarily from private and institutional investors.
Traumdarstellungen in Büchern und Filmen mit ›ambiguem‹ Ende sind in der Populärkultur seit den 1990er-Jahren beliebt. (Kuhn 2009, S. 141 f.) Man kann die Popularität solcher plot-Strukturen durchaus plausibel als Reaktion der Kunst auf die zunehmende Komplexität der Gesellschaft (Berndt / Koepnick 2018, S. 7) deuten. Diese Komplexitätssteigerung ergibt sich beispielsweise durch die Möglichkeiten digitaler Technologien, neben der wirklichen Welt auch virtuelle Welten, eine virtual, mixed oder augmented reality, zu kreieren, in denen sich die Grenze zwischen Realität und Fiktion verschiebt.
Gstöttl, Claudia ; Stoldt, Marah ; Jongepier, Evelien ; Bornberg-Bauer, Erich ; Feldmeyer, Barbara ; Heinze, Jürgen ; Foitzik, Susanne
Social insects dominate arthropod communities worldwide due to cooperation and division of labor in their societies. This, however, makes them vulnerable to exploitation by social parasites, such as slave‐making ants. Slave‐making ant workers pillage brood from neighboring nests of related host ant species. After emergence, host workers take over all nonreproductive colony tasks, whereas slavemakers have lost the ability to care for themselves and their offspring. Here, we compared transcriptomes of different developmental stages (larvae, pupae, and adults), castes (queens and workers), and sexes of two related ant species, the slavemaker Temnothorax americanus and its host Temnothorax longispinosus. Our aim was to investigate commonalities and differences in group‐specific transcriptomes, whereupon across‐species differences possibly can be explained by their divergent lifestyles. Larvae and pupae showed the highest similarity between the two species and upregulated genes with enriched functions of translation and chitin metabolism, respectively. Workers commonly upregulated oxidation‐reduction genes, possibly indicative of their active lifestyle. Host workers, but not workers of the slavemaker, upregulated a “social behavior” gene. In slavemaker queens and workers, genes associated with the regulation of transposable elements were upregulated. Queens of both species showed transcriptomic signals of anti‐aging mechanisms, with hosts upregulating various DNA repair pathways and slavemaker queens investing in trehalose metabolism. The transcriptomes of males showed enriched functions for quite general terms realized in different genes and pathways in each species. In summary, the strong interspecific commonalities in larvae, pupae, and workers were reflected in the same enriched Gene Ontology (GO) terms. Less commonalities occurred in the transcriptomes of queens and males, which apparently utilize different pathways to achieve a long life and sperm production, respectively. We found that all analyzed groups in this study show characteristic GO terms, with similar patterns in both species.
Gudbrandsen, Maria ; Daly, Eileen ; Murphy, Clodagh M. ; Blackmore, Charlotte ; Rogdaki, Maria ; Mann, Catrin ; Bletsch, Anke ; Kushan, Leila ; Bearden, Carrie E. ; Murphy, Declan G. M. ; Craig, Michael ; Ecker, Christine
22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion in humans, with a heterogenous clinical presentation including medical, behavioural and psychiatric conditions. Previous neuroimaging studies examining the neuroanatomical underpinnings of 22q11.2DS show alterations in cortical volume (CV), cortical thickness (CT) and surface area (SA). The aim of this study was to identify (1) the spatially distributed networks of differences in CT and SA in 22q11.2DS compared to controls, (2) their unique and spatial overlap, as well as (3) their relative contribution to observed differences in CV. Structural MRI scans were obtained from 62 individuals with 22q11.2DS and 57 age-and-gender-matched controls (aged 6–31). Using FreeSurfer, we examined differences in vertex-wise estimates of CV, CT and SA at each vertex, and compared the frequencies of vertices with a unique or overlapping difference for each morphometric feature. Our findings indicate that CT and SA make both common and unique contributions to volumetric differences in 22q11.2DS, and in some areas, their strong opposite effects mask differences in CV. By identifying the neuroanatomic variability in 22q11.2DS, and the separate contributions of CT and SA, we can start exploring the shared and distinct mechanisms that mediate neuropsychiatric symptoms across disorders, e.g. 22q11.2DS-related ASD and/or psychosis/schizophrenia.
Phenomenological sociology is one of the most recognized approaches for explaining the constitution of social behaviour and the construction of social reality. To this day, phenomenological sociology usually belongs to the tradition of Edmund Husserl's transcendental phenomenology and to Alfred Schütz's mundane phenomenology, thus generally presenting itself as sociology of lifeworld, sociology of everyday life, and sociology of knowledge. In contrast to this, this paper intends to outline an alternative kind of phenomenological sociology that finds its philosophical foundation in Hermann Schmitz's “New Phenomenology”. With regards especially to Schmitz's theory of the felt body (“Leib”) and his theory of situation, the basic principles of Neophenomenological Sociology (NPS) will be introduced. Their main components are (1) felt body and affective involvement as the pre‐personal apriori of sociality, (2) felt‐bodily communication as the basic unit of sociality, and (3) joint situations as the socio‐ontological foundation and empirical manifestation of sociality. With these specific key concepts, NPS proves itself to be a socio‐theoretical approach whose foremost strength is that it can identify and properly analyse the pathic dimensions of social behaviour and social situations that social sciences tend to overlook.
Impact parameter sensitive study of inner-shell atomic processes in Xe54+, Xe52+ → Xe collisions
(2020)
Gumberidze, Alexandre ; Kozhuharov, Christophor ; Zhang, Ruitian ; Trotsenko, Sergiy ; Kozhedub, Yury S. ; DuBois, Robert D. ; Beyer, Heinrich F. ; Blumenhagen, Karl-Heinz ; Brandau, Carsten ; Bräuning-Demian, Angela ; Chen, Weidong ; Forstner, Oliver ; Gao, Bingshui ; Gaßner, Tobias ; Grisenti, Robert Evaristo ; Hagmann, Siegbert ; Hillenbrand, Pierre-Michel ; Indelicato, Paul ; Kumar, Ajay ; Lestinsky, Michael ; Litvinov, Yuri A. ; Petridis, Nikolaos ; Schury, Daniel ; Spillmann, Uwe ; Trageser, Christian ; Trassinelli, Martino ; Tu, Xiaolin ; Stöhlker, Thomas
In this work, we present a pilot experiment in the experimental storage ring (ESR) at GSI devoted to impact parameter sensitive studies of inner shell atomic processes for bare and He-like xenon ions (Xe54+, Xe52+) colliding with neutral xenon gas atoms. The projectile and target x-rays have been measured at different observation angles for all impact parameters as well as for the impact parameter range of ∼35 - 70 fm.
Gunne, Sandra ; Heinicke, Ulrike ; Parnham, Michael J. ; Laux, Volker ; Zacharowski, Kai ; Knethen, Andreas von
The transcription factor NF-E2 p45-related factor 2 (Nrf2) is an established master regulator of the anti-oxidative and detoxifying cellular response. Thus, a role in inflammatory diseases associated with the generation of large amounts of reactive oxygen species (ROS) seems obvious. In line with this, data obtained in cell culture experiments and preclinical settings have shown that Nrf2 is important in regulating target genes that are necessary to ensure cellular redox balance. Additionally, Nrf2 is involved in the induction of phase II drug metabolizing enzymes, which are important both in degrading and converting drugs into active forms, and into putative carcinogens. Therefore, Nrf2 has also been implicated in tumorigenesis. This must be kept in mind when new therapy approaches are planned for the treatment of sepsis. Therefore, this review highlights the function of Nrf2 in sepsis with a special focus on the translation of rodent-based results into sepsis patients in the intensive care unit (ICU).
The Early Permian coal is of great value in the Tengxian Coalfield, Shandon Province, Eastern China. This work deals with the new data focusing on mineralogical characteristics in the Early Permian Shanxi Formation No. 3 coal from the Jinyuan Mine. The Jinyuan coal is a low ash and highly volatile A bituminous coal. Minerals in the No. 3 coal mainly comprise of kaolinite, ankerite, illite, calcite, siderite, and quartz, with varying compositions of trace amounts of pyrite, jarosite, bassanite, anatase, and rutile. According to mineral assemblage in the coal plies, three Types (A to C) can be identified in the No. 3 coal. The dominant minerals in Type A are poorly-ordered kaolinite, illite, quartz, pyrite, and jarosite. Type B is mainly composed of well-ordered kaolinite, illite, siderite, ankerite, and calcite. Type C, with just one sample (JY-3-7c), which contains high proportions of calcite (54%) and ankerite (34%). Terrigenous minerals are elevated in coal plies that typically have relatively high contents of ash yield. The formation of syngenetic pyrite was generally due to seawater, while the sulphate minerals (jarosite and coquimbite) were derived from the oxidation of pyrite. Epigenetic vein-like or fracture-fillings carbonate minerals (ankerite, calcite, and siderite), kaolinite, and pyrite, as well as authigenic quartz were derived from the influx of hydrothermal fluids during different periods, from the authigenic to epigenetic. The paragonite in the coal may have been formed by the precipitated from Na-rich hydrothermal fluids. No effects of magmatic intrusion on mineralogy were investigated in this research.
Diese Arbeit beschäftigt sich mit der theoriegeleiteten Entwicklung eines digitalen Werkzeugs namens MathCityMap (MCM) für das außerschulische Lehren und Lernen von Mathematik.
Den Ausgangspunkt des Projekts bilden die sogenannten Mathtrails. Dies sind Wanderpfade zum Entdecken mathematischer Sachverhalte an realen Objekten in der Umwelt. Eine didaktische, methodische sowie lernpsychologische Analyse konstatiert Mathtrails zahlreiche Potentiale für den Lernprozess wie beispielsweise die Möglichkeit, Primärerfahrungen zu sammeln, das Interesse am Fach Mathematik zu steigern sowie das Lernen aktiv und konstruktiv zu gestalten. Trotz der genannten Vorteile wird deutlich, dass die Vorbereitung und Umsetzung der mathematischen Wanderpfade mit einem immensen Aufwand verbunden sind. Eine weitere Herausforderung für Lernende liegt im offenen Charakter der Mathtrails, die in der Regel in autonomen Kleingruppen abgelaufen werden. Aus der Literatur ist bekannt, dass insbesondere für schwächere Lerner die Gefahr besteht, durch die Anforderungen einer selbstständigen Arbeitsweise überfordert zu werden.
Als Lösungsansatz für die zuvor genannten Probleme wird im Rahmen dieser Arbeit die Entwicklung eines digitalen Werkzeugs für Mathtrails erläutert. Die erste Forschungsfrage beschäftigt sich mit den theoretischen Anforderungen an solch ein Tool:
1. Welchen Anforderungen muss ein digitales Werkzeug genügen, um die Vorzüge der Mathtrails zu erhalten, deren Aufwand zu minimieren und die Gefahren zu kompensieren?
Unter Berücksichtigung der theoretischen Grundlagen digitaler Werkzeuge und des „Mobile Learnings“ werden zunächst Möglichkeiten identifiziert, den Vorbereitungsaufwand zu minimieren. Konkret erscheinen die automatische Datenverarbeitung, das digitale Zusammen-arbeiten sowie das Teilen und Wiederverwenden von digitalen Aufgaben und Trails als theoretisch zielführende Bestandteile von MCM. Weiterhin sollen zur Unterstützung der Lerner bei der eigenständigen Bearbeitung von Mathtrails didaktisch bewährte Konzepte – wie gestufte Hilfestellungen und Feedback – eingesetzt werden.
Vor dem Hintergrund der soeben formulierten Anforderungen bilden der Entwicklungsprozess sowie die Beschreibung des aktuellen Ist-Zustandes des MCM-Systems zentrale Bestand-teile dieser Arbeit. Das System setzt sich aus zwei Komponenten für jeweils unterschiedliche Zielgruppen zusammen: das MCM-Webportal zum Erstellen von Mathtrails und die MCM-App zum Ablaufen selbiger. Die Hauptziele von MCM können in der Minimierung des Vorbereitungsaufwands sowie der Kompensation einer Überforderungsgefahr gesehen werden.
In ersten Feldversuchen konnte MCM bereits in einem frühen Stadium erfolgreich mit Lernenden der Sekundarstufe I getestet werden. Gleichzeitig fiel jedoch auf, dass das implementierte Feedback-System Schwächen aufwies und von Lernenden zum systematischen Erraten von Lösungen genutzt werden konnte. In der Folge wurden Spielelemente (Gamification), denen nicht nur eine motivationssteigernde Wirkung nachgesagt wird, sondern auch das Potential das Verhalten zu beeinflussen, Bestandteil der MCM-App. Die zweite Forschungs-frage dieser Arbeit zielt auf die Auswirkungen der Gamification-Integration ab und lautet:
2. Welchen Einfluss haben Gamification-Elemente auf die Motivation sowie auf das Nutzungs-verhalten des digitalen Werkzeugs von Neuntklässlern bei der Bearbeitung eines Mathtrails?
Zur Beantwortung der zweiten Forschungsfrage wurde eine empirische Studie mit 16 Schulklassen (304 Schülerinnen und Schüler) der neunten Jahrgangsstufe im Sommer 2017 durch-geführt. Die Ergebnisse können wie folgt zusammengefasst werden: Die Implementierung einer Rangliste (Leaderboard) in die MCM-App führte zwar nicht zu einer höheren Motivation, jedoch spornte der Wettbewerb die Teilnehmer an, viele Aufgaben zu bearbeiten. Im Ver-gleich zu der Kontrollgruppe ohne Gamification-Elemente löste die Experimentalgruppe signifikant mehr Aufgaben, legte die doppelte Strecke zurück und nutzte das Feedbacks-System seltener aus, um Lösungen zu erraten. Die Studie konnte empirisch den gewünschten Einfluss von Spielelementen auf die Benutzung eines digitalen Werkzeugs für das außerschulische Lernen von Mathematik aufzeigen.
Die Evaluation der Ziele von MCM erfolgt indirekt über die Analyse der Verbreitung der Mathtrail-Idee ohne MCM und mit MCM. Die dritte Forschungsfrage lautet dementsprechend:
3. Welchen Beitrag hat das digitale Werkzeug zur Verbreitung der Mathtrail-Idee nach 4 Jahren Projektlaufzeit geleistet?
Zur Beantwortung der dritten Forschungsfrage werden wissenschaftliche Publikationen zu Mathtrails analysiert. Es wird insbesondere in Publikationen mit und ohne Stichwort „MathCityMap“ unterschieden, um eine Aussage über den Einfluss des MCM-Projekts auf den wissenschaftlichen Diskurs treffen zu können. Stand August 2020 enthält bereits jede dritte Mathtrail-Publikation einen Bezug zu MCM. Weiterhin wird ein Vergleich zu vorherigen, ähnlichen Bemühungen – gemeint sind Online-Mitmach-Projekte für Mathtrails – gezogen. So existierten im Zeitraum 2000 bis 2010 im anglo-amerikanischen Raum erste Webseiten für mathematische Wanderpfade. Diese boten zusammengenommen 131 Mathtrails an. Im Vergleich hierzu existieren bereits über 2.500 MCM-Mathtrails in 57 Ländern.
Sowohl die Publikationen als auch die Anzahl der erstellten Trails stellen erste Indizien dafür dar, dass mit MCM die Realisation eines theoretischen Konzepts für ein digitales Mathtrail-Werkzeug gelungen ist und die Idee der Mathtrails verbreitet werden konnte.
Dental clinics were suspected to be a hotspot for nosocomial transmission of coronavirus disease 19 (COVID-19), yet there has been no clear recommendation about emergency dental care and appropriate personal protective equipment during pandemics. In this paper, we aim to summarize recommendations for (i) patient risk assessment, (ii) patient triage, and (iii) measures to prevent infection of health professionals and nosocomial transmission in dental clinics. The available evidence was collected by performing searches on PubMed, Embase, and Cochrane databases. We reviewed papers on COVID-19, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), influenza, and related respiratory viral diseases. Legal and ethical frameworks, as well as international (e.g., World Health Organization (WHO)) and national (e.g., public health institutes, dental associations) guidelines were screened to summarize recommendations related to dental emergency care. To assess the patient risk, a questionnaire was developed to classify patients at unknown, high, and very high risk. Patient triage recommendations were summarized in a flow chart that graded the emergency level of treatments (i.e., urgent, as soon as possible, and postpone). Measures to prevent disease transmission based on current evidence were grouped for dental health professionals, dental clinics, and patients. The present recommendations may support health professionals implement preventative measures during the pandemic.
Am Beispiel des politisch-planerischen Diskurses zu ehemaligen Planungen für ein großflächiges Einkaufszentrum in der Mainzer Innenstadt wird der potenzielle Mehrwert diskurs- und gouvernementalitätstheoretischer Zugänge zu raumbezogenen Fragestellungen erörtert. Insbesondere werden die diskursiven Mechanismen der Einschreibung einer unternehmerischen und depolitisierten Konzeption urbaner Räume in scheinbar neutrale und objektive Techniken raumbezogener Wirkungsanalysen herausgearbeitet. Die damit verbundene Sichtweise auf städtische Räume als Wettbewerbseinheiten, die durch raumwirtschaftliche Gesetzmäßigkeiten determiniert sind, wird jedoch gleichzeitig durch Gegendiskurse aufgebrochen, die das Bewahren ortsspezifisch gewachsener baulicher Strukturen zum Maßstab von Stadtentwicklungspolitik machen. Die Fallstudie verdeutlicht damit, wie mithilfe diskursanalytischer Zugänge die raumbezogenen Wissensordnungen freigelegt werden können, die die politischplanerische Steuerung gegenwärtiger Stadtentwicklungsprozesse anleiten.
Young neurons in the adult brain are key to some types of learning and memory. They integrate in the dentate gyrus (DG) of the hippocampus contributing to such cognitive processes following timely developmental events. While experimentally impairing GABAergic transmission through the blockade or elimination of the ionic cotransporter NKCC1 leads to alterations in the proper maturation of young neurons, it is still unknown if the in vivo administration of common use diuretic drugs that block the cotransporter, alters the development of young hippocampal neurons and affects DG-related functions. In this study, we delivered chronically and intracerebroventricularly the NKCC1 blocker bumetanide to young-adult rats. We analyzed doublecortin density and development parameters (apical dendrite length and angle and dendritic arbor length) in doublecortin positive neurons from different subregions in the DG and evaluated the performance of animals in contextual fear learning and memory. Our results show that in bumetanide-treated subjects, doublecortin density is diminished in the infra and suprapyramidal blades of the DG; the length of primary dendrites is shortened in the infrapyramidal blade and; the growth angle of primary dendrites in the infrapyramidal blade is different from control animals. Behaviorally, treated animals showed the typical learning curve in a contextual fear task, and freezing-time displayed during contextual fear memory was not different from controls. Thus, in vivo icv delivery of bumetanide negatively alters DCX density associated to young neurons and its proper development but not to the extent of affecting a DG dependent task as aversive context learning and memory.
Göbel, Kathrin ; Heil, Michael ; Bott, Lukas ; Brandenburg, Leonard ; Caesar, Christoph ; Deuter, Isabell ; Grein, Alexander ; Keliç-Heil, Aleksandra ; Körper, Daniel ; Löher, Bastian ; Reifarth, René ; Savran, Deniz ; Schulte, Hendrik ; Simon, Haik ; Törnqvist, Hans Toshihide ; Almusidi, Tahani ; Álvarez-Pol, Héctor ; Atkins, Liam ; Aumann, Thomas ; Bemmerer, Daniel ; Benlliure Anaya, Jose Fernando ; Boretzky, Konstanze ; Brückner, Benjamin ; Cabanelas Eiras, Pablo ; Casarejos Ruiz, Enrique ; Cederkäll, Joakim ; Chulkov, Leonid V. ; Cortina Gil, Dolores ; Danilov, Andrey ; Erbacher, Philipp ; Escribano Rodriguez, Sonia ; Fülöp, Zsolt ; Falduto, Ashton ; Fiebiger, Stefan ; Gašparić, Igor ; Garcia Borge, Maria José ; Gernhäuser, Roman ; Glorius, Jan ; Gonzales Caamaño, David ; Hartig, Anna-Lena ; Heftrich, Tanja ; Heggen, Henning ; Heine, Marcel ; Heinz, Andreas ; Hensel, Thomas ; Holl, Matthias ; Johansson, Håkan T. ; Jonson, Björn ; Kalantar-Nayestanaki, Nasser ; Kamenyero, Armel ; Khasawneh, Kafa al- ; Kiselev, Oleg A. ; Klenze, Philipp ; Kohls, Marvin ; Kröll, Thorsten ; Kresan, Dmytro ; Kurtulgil, Cem Deniz ; Kurz, Nikolaus ; Langer, Christoph ; Lehr, Christopher ; Litvinov, Yuri A. ; Lorenz, Enis ; Murillo Morales, Silvia ; Nácher González, Enrique ; Nilsson, Thomas ; Park, Joochun ; Paschalis, Stefanos ; Perea Martinez, Angel ; Petri, Marina ; Plag, Ralf ; Ponnath, Lukas ; Popočovski, Romana ; Reich, Markus ; Rhee, Han-Bum ; Rodriguez Sanchez, Jose Luis ; Rossi, Dominic M. ; Scheit, Heiko ; Schmidt, Konrad ; Slavkovská, Zuzana ; Starostin, Viktor ; Storck, Sonja ; Sürder, Christian ; Tanaka, Junki ; Tengblad, Olof ; Thomas, Benedikt ; Typel, Stefan ; Varga, László ; Volk, Klaus ; Volknandt, Meiko ; Wagner, Vadim ; Wamers, Felix ; Weigand, Mario ; Zanetti, Lorenzo
We measured the Coulomb dissociation of 16O into 4He and 12C at the R3B setup in a first campaign within FAIR Phase 0 at GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt. The goal was to improve the accuracy of the experimental data for the 12C(α,γ)16O fusion reaction and to reach lower center-ofmass energies than measured so far.
The experiment required beam intensities of 109 16O ions per second at an energy of 500 MeV/nucleon. The rare case of Coulomb breakup into 12C and 4He posed another challenge: The magnetic rigidities of the particles are so close because of the same mass-to-charge-number ratio A/Z = 2 for 16O, 12C and 4He. Hence, radical changes of the R3B setup were necessary. All detectors had slits to allow the passage of the unreacted 16O ions, while 4He and 12C would hit the detectors' active areas depending on the scattering angle and their relative energies. We developed and built detectors based on organic scintillators to track and identify the reaction products with sufficient precision.
Gökbuget, Nicola ; Zugmaier, Gerhard ; Dombret, Hervé ; Stein, Anthony ; Bonifacio, Massimiliano ; Graux, Carlos ; Faul, Christoph ; Brüggemann, Monika ; Taylor, Kate ; Mergen, Noemi ; Reichle, Albrecht ; Horst, Heinz August ; Havelange, Violaine ; Topp, Max S. ; Bargou, Ralf C.
Minimal residual disease (MRD) is the strongest predictor of relapse in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In BLAST study (NCT01207388), adults with BCP-ALL in remission with MRD after chemotherapy received blinatumomab, a CD19 BiTE® immuno-oncotherapy, 15 µg/m2/day for up to four 6-week cycles (4 weeks continuous infusion, 2 weeks off). Survival was evaluated for 110 patients, including 74 who received HSCT in continuous complete remission. With a median follow-up of 59·8 months, median survival (months) was 36·5 (95% CI: 22.0–not reached [NR]). Median survival was NR (29.5–NR) for complete MRD responders (n = 84) and 14.4 (3.8–32.3) for MRD non-responders (n = 23; p = 0.002); after blinatumomab and HSCT, median survival was NR (25.7–NR) (n = 61) and 16.5 (1.1–NR) (n = 10; p = 0.065), respectively. This final analysis suggests complete MRD response during blinatumomab treatment is curative. Post-hoc analysis of study data suggests while post blinatumomab HSCT may be beneficial in appropriate patients, long-term survival without HSCT is also possible.
Görlich, Nina ; Brand, Hannah Antonia ; Langhans, Valerie ; Tesch, Sebastian ; Schachtner, Thomas ; Koch, Benjamin Florian ; Paliege, Alexander ; Schneider, Wolfgang ; Grützkau, Andreas ; Reinke, Petra ; Enghard, Philipp
Creatinine and proteinuria are used to monitor kidney transplant patients. However, renal biopsies are needed to diagnose renal graft rejection. Here, we assessed whether the quantification of different urinary cells would allow non-invasive detection of rejection. Urinary cell numbers of CD4+ and CD8+ T cells, monocytes/macrophages, tubular epithelial cells (TEC), and podocalyxin(PDX)-positive cells were determined using flow cytometry and were compared to biopsy results. Urine samples of 63 renal transplant patients were analyzed. Patients with transplant rejection had higher amounts of urinary T cells than controls; however, patients who showed worsening graft function without rejection had similar numbers of T cells. T cells correlated with histological findings (interstitial inflammation p = 0.0005, r = 0.70; tubulitis p = 0.006, r = 0.58). Combining the amount of urinary T cells and TEC, or T cells and PDX+ cells, yielded a significant segregation of patients with rejection from patients without rejection (all p < 0.01, area under the curve 0.89–0.91). Urinary cell populations analyzed by flow cytometry have the potential to introduce new monitoring methods for kidney transplant patients. The combination of urinary T cells, TEC, and PDX-positive cells may allow non-invasive detection of transplant rejection.
Die wesentliche Glaubenslehre des Islam ist das Bekenntnis der Einheit Gottes (Tawḥīd). Jalāluddīn Rūmī (g. 1273) erzählt in einer der längsten Geschichten seiner Maṯnawī die geistige Entwicklung des Menschen, bis er von Zwiespalt, Zweifel und Sorge befreit wird und so Tawḥīd, d.h. Einheit und Frieden in sich erreicht. Die Geschichte des Wüstenarabers (A‛rābī) und seiner Frau, welche in diesem Artikel behandelt wird, legt die Stufen der geistigen Reise, das Voranschreiten der Seele zur Einheit und hierbei das Verhältnis von Vernunft und Seele des Menschen, die als ein Ehepaar versinnbildlicht werden, dar.
Die zunehmende Durchdringung nahezu aller Lebensbereiche der Gesellschaft mit neuen digitalen Technologien, insbesondere mit künstlicher Intelligenz, hat zur Entstehung von smarten Ordnungen geführt. Darunter werden Ordnungen verstanden, die darauf ausgerichtet sind, durch intelligentes Design und mit Hilfe algorithmischer Operationen Abweichungen von ihren Normen zu minimieren oder ganz unmöglich zu machen. Der Beitrag erläutert einige Beispiele smarter Ordnungen und zeigt auf, dass zumindest im Grundsatz zwischen einer algorithmisch optimierten, normadressatenorientierten Prävention und einer adressatensubstituierenden Präemption abweichenden Verhaltens durch digitale Technologien unterschieden werden kann. Den Schwerpunkt des Beitrags bildet sodann die Frage ob und, gegebenenfalls, in welchem Sinne, smarte Ordnungen überhaupt noch normative Ordnungen sind. Im Verlauf der Analyse zeigt sich, dass Rechtsordnungen und andere normative Ordnungen zwar das Ziel einer effektiven Durchsetzung ihrer Normen verfolgen, aber nicht das Ideal vollständiger Nicht-Abweichung. Es wird deutlich, dass es zu den wesentlichen Aspekten normativer Ordnungen gehört, dass sie an Personen adressiert sind, die sie sich als autonome und zugleich fehlbare Personen zu eigen machen müssen und dabei unvermeidlich über die faktische Freiheit zur Normabweichung verfügen. Smarte Ordnungen hingegen erfüllen diese Kriterien nicht oder nur in geringem Maße. Letztlich sind sie nur in einem schwachen Sinne normativ, soweit die in technischen Prozessen implementierte Normativität für die Betroffenen noch präsent ist. In dem Maße jedoch, wie Normativität und ihre technische Realisation sich vermischen, bis ihre erfahrbare Präsenz abnimmt, verlieren sie ihren normativen Charakter.
Die Zukunft der Freiheit
(2020)
Im Zentrum des Beitrags steht die Frage, ob und wie sich Freiheit verändert, wenn wir uns in Echo-Räumen bewegen, also in digitalen sozialen Netzwerken und in digitalen Welten, die aus den Vorhersagedaten des eigenen Verhaltens zusammengesetzt sind. Beide Varianten digitaler Welten werden als Bestätigungswelten charakterisiert, in denen der Nutzer sich in relevanten Aspekten seines Selbst nicht nur spiegelt, sondern immer wieder bestätigt und anerkannt sieht und auch andere bestätigt und anerkennt. Der Aufsatz verdeutlicht, dass es für die Frage der Freiheit in solchen Bestätigungswelten nicht nur darauf ankommt, ob wir nach den jeweils eigenen Gründen handeln oder nach Regeln, die wir gemeinsam mit anderen akzeptieren können. Denn solche Ansätze beruhen auf der unausgesprochenen Prämisse eines statischen Selbst, eine so verstandene Freiheit wäre eine statische Freiheit. Dem wird ein Verständnis von Freiheit als dynamischer Prozess gegenübergestellt, zu dem es gehört, die eigenen Gründe zu ändern. Dazu muss sich das Selbst von diesen Gründen aber erst einmal distanzieren und sich zu sich selbst verhalten können, was die Erfahrung von Widerspruch und Widerstand voraussetzt. Komplementär zu diesem Widerspruch ist es zudem auf Vertrauen angewiesen, um die Herausforderungen der Freiheit anzunehmen. Es wird gezeigt, dass sich beide Aspekte, die Freiheit als Risiko des Widerspruchs und das für die Freiheit notwendige komplementäre Vertrauen, in den digitalen Bestätigungswelten verflüchtigen.
Leider geschlossen! Theater spielt sich normalerweise auf der Bühne und im besten Fall vor ausverkauftem Haus ab. Da gerade nichts normal ist und die Spielstätten geschlossen sind, versuchen viele Schauspielhäuser ihren kulturellen Beitrag online zu leisten. Ein kurzer Einblick in digitale Wege der Schauspielkunst zu Krisenzeiten.
Hurra die Welt geht unter! Zwar sitzen wir noch nicht im Atomschutzbunker, aber tausende Menschen sind auf der Flucht, es herrscht ein globaler Kampf um Ressourcen und die Welt ertrinkt im Müll. Die Ausstellung "Making Crisis Visible" wirft einen spektralen Blick auf das Potential, das Krisenzeiten innewohnt.
Central banks unexpectedly tightening policy rates often observe the exchange value of their currency depreciate, rather than appreciate as predicted by standard models. We document this for Fed and ECB policy days using event studies and ask whether an information effect, where the public attributes the policy surprise to an unobserved state of the economy that the central bank is signaling by its policy may explain the abnormality. It turns out that many informational assumptions make a standard two- country New Keynesian model match this behavior. To identify the particular mechanism, we condition on multiple asset prices in the event study and model implications for these. We find that there is heterogeneity in this dimension in the event study and no model with a single regime can match the evidence. Further, even after conditioning on possible information effects driving longer term interest rates, there appear to be other drivers of exchange rates. Our results show that existing models have a long way to go in reconciling event study analysis with model-based mechanisms of asset pricing.
Haas, Yvonne ; Naser, Antonia ; Haenel, Jasmin ; Fräulin, Laura ; Holzgreve, Fabian Christian ; Erbe, Christina ; Betz, Werner ; Wanke, Eileen M. ; Brüggmann, Dörthe ; Nienhaus, Albert ; Groneberg, Jan David Alexander ; Ohlendorf, Daniela Maren
Background: Dental professionals are subjected to higher risks for musculoskeletal disorders (MSDs) than other professional groups, especially the hand region. This study aims to investigate the prevalence of hand complaints among dentists (Ds) and dental assistants (DAs) and examines applied therapies. Methods: For this purpose, an online questionnaire analysed 389 Ds (240female/149male) and 406 DAs (401female/5male) working in Germany. The self-reported data of the two occupational groups were compared with regard to the topics examined. The questionnaire was based on the Nordic Questionnaire (self-reported lifetime, 12-month and 7-day MSDs prevalence of the hand, the conducted therapy and its success), additional occupational and sociodemographic questions as well as questions about specific medical conditions. Results: 30.8% of Ds affirmed MSDs in the hand at any time in their lives, 20.3% in the last twelve months and 9.5% in the last seven days. Among DAs, 42.6% reported a prevalence of MSDs in the hand at any time in their lives, 31.8% in the last 12 months and 15.3% in the last seven days. 37.5% of the Ds and 28.3% of the DAs stated that they had certain treatments. For both, Ds and DAs, physiotherapy was the most frequently chosen form of therapy. 89.7% of Ds and 63.3% of DAs who received therapy reported an improvement of MSDs. Conclusion: Although the prevalence of MSDs on the hand is higher among DAs than among Ds, the use of therapeutic options and the success of therapy is lower for DAs compared to Ds.
Current evidence indicates that acute aerobic exercise might increase domain-specific cognitive performance. However, only a small number of studies deduced the impact on lower and higher cognitive functions systematically or analyzed dose–response relationships and the underlying mechanisms. This study aimed to expose the dose–response relationships by investigating the influence of exercise duration on subjective and objective arousal, cognitive attention and visual recognition memory tasks. Nineteen participants (eight female; 25.69 ± 3.11 years) were included in a randomized, three-armed intervention study in a cross-over design. The participants completed three different interventions consisting of either 15, 30 or 45 min of cycling at 60–70% VO2max. Arousal and cognitive measurements were taken before and immediately after (<2 min) exercise. All three interventions led to significant but comparable effects on self-perceived arousal, heart rate (HR) and rating of perceived exertion (RPE) (p < 0.05). Analysis of variance (ANOVA) indicated significant effects of exercise duration on visual recognition memory accuracy. Reaction times for higher and lower cognitive tasks did not change after exercise. Fifteen minutes of aerobic exercise was feasible to induce beneficial changes in self-perceived arousal. Processing speed of visual recognition memory and attention remained unaltered. Exercise exceeding fifteen minutes seemed to negatively impact visual recognition memory accuracy.
Incentivized experiments in which individuals receive monetary rewards according to the outcomes of their decisions are regarded as the gold standard for preference elicitation in experimental economics. These task-related real payments are considered necessary to reveal subjects' "true preferences". Using a systematic, large-sample approach with three subject pools of private investors, professional investors, and students, we test the effect of task-related monetary incentives on risk preferences elicited in four standard experimental tasks. We find no systematic differences in behavior between subjects in the incentivized and non-incentivized regimes. We discuss implications for academic research and for applications in the field.
In diesem Beitrag wird ein Vorschlag vorgestellt, wie es trotz langfristiger Niedrigzinsen möglich ist, die vor 18 Jahren eingeführte Riester-Rente so umzugestalten, dass alle Beteiligten davon profitieren. Wird die Mindestauszahlung am Ende der Vertragslaufzeit nur für die Eigenbeiträge, nicht aber für die staatlichen Zulagen garantiert, können deutlich höhere Renditen erzielt werden. Unter dem Strich haben dann nicht nur Privatleute mehr Geld aus ihrer Altersvorsorge, sondern der Staat wird mehr Steuern einnehmen und die Anbieter haben mehr Spielraum für bedarfsgerechte Produktgestaltung.
Fiscal policies and household consumption during the COVID-19 pandemic: a review of early evidence
(2020)
We review early evidence on how household consumption behavior has evolved over the pandemic and how different groups of households have responded to fiscal stimulus programs. Due to the scarcity of evidence for Europe, our review focuses on evidence from the US. Notwithstanding the institutional and demographic differences, we highlight generalizable findings and challenges to the design of stimulus policies from the pandemic. In conclusion, we identify several open issues for dis cussion.
This systematic review investigated how successful children/adolescents with poor literacy skills learn a foreign language compared with their peers with typical literacy skills. Moreover, we explored whether specific characteristics related to participants, foreign language instruction, and assessment moderated scores on foreign language tests in this population. Overall, 16 studies with a total of 968 participants (poor reader/spellers: n = 404; control participants: n = 564) met eligibility criteria. Only studies focusing on English as a foreign language were available. Available data allowed for meta-analyses on 10 different measures of foreign language attainment. In addition to standard mean differences (SMDs), we computed natural logarithms of the ratio of coefficients of variation (CVRs) to capture individual variability between participant groups. Significant between-study heterogeneity, which could not be explained by moderator analyses, limited the interpretation of results. Although children/adolescents with poor literacy skills on average showed lower scores on foreign language phonological awareness, letter knowledge, and reading comprehension measures, their performance varied significantly more than that of control participants. Thus, it remains unclear to what extent group differences between the foreign language scores of children/adolescents with poor and typical literacy skills are representative of individual poor readers/spellers. Taken together, our results indicate that foreign language skills in children/adolescents with poor literacy skills are highly variable. We discuss the limitations of past research that can guide future steps toward a better understanding of individual differences in foreign language attainment of children/adolescents with poor literacy skills.
Signature of consciousness in brain-wide synchronization patterns of monkey and human fMRI signals
(2020)
Hahn, Gerald ; Zamora-López, Gorka ; Uhrig, Lynn ; Tagliazucchi, Enzo ; Laufs, Helmut ; Mantini, Dante ; Kringelbach, Morten L. ; Jarraya, Bechir ; Deco, Gustavo
During the sleep-wake cycle, the brain undergoes profound dynamical changes, which manifest subjectively as transitions between conscious experience and unconsciousness. Yet, neurophysiological signatures that can objectively distinguish different consciousness states based are scarce. Here, we show that differences in the level of brain-wide signals can reliably distinguish different stages of sleep and anesthesia from the awake state in human and monkey fMRI resting state data. Moreover, a whole-brain computational model can faithfully reproduce changes in global synchronization and other metrics such as functional connectivity, structure-function relationship, integration and segregation across vigilance states. We demonstrate that the awake brain is close to a Hopf bifurcation, which naturally coincides with the emergence of globally correlated fMRI signals. Furthermore, simulating lesions of individual brain areas highlights the importance of connectivity hubs in the posterior brain and subcortical nuclei for maintaining the model in the awake state, as predicted by graph-theoretical analyses of structural data.
Die Aufdeckung krankheitsbedingter Unterschiede und die Identifizierung neuer Biomarker sind essenziell für Diagnose und Behandlung verschiedener Erkrankungen. Unterschiede zwischen Erkrankungen können u.a. durch Analyse des Lipidprofils aufgedeckt werden, da dieses eng mit dem Phänotyp verknüpft ist. Ein unvoreingenommenes Screening gewährt einen umfassenderen Einblick in den metabolischen Zustand als eine gezielte Untersuchung weniger Analyten und kann neue Hypothesen generieren. Deshalb wurde im Rahmen dieser Arbeit eine Screening-Methode zur untargeted Untersuchung des Lipidoms in biologischen Proben entwickelt. Durch die Kombination aus Umkehrphasenchromatographie und hochauflösender Massenspektrometrie mit datenabhängiger Aufnahme von MS/MS-Spektren konnten in Humanplasma 440 Lipide aus mehr als 15 Lipidklassen identifiziert werden. Die mehrstufige Identifizierung der Analyten, basierend auf der exakten Masse ±5 ppm, der Isotopenverteilung, der MS/MS-Fragmentierungsmuster in beiden Ionisationsmodi sowie der chromatographischen Auftrennung von Isomeren und Isobaren, erfolgte mit hoher Selektivität. Mit der vorgestellten Methode können sowohl Lipidklassen als auch einzelne Lipide relativ zu den internen Standards quantifiziert werden.
Der Probendurchsatz wurde erhöht, um den Einsatz der Methode im Rahmen größerer klinischer Studien zu ermöglichen und vorhandene Ressourcen effizient einzusetzen. Dabei wurden die Inkubationszeiten während der Flüssig-Flüssig-Extraktion mit MTBE:Methanol deutlich reduziert und die Handhabung vereinfacht bei gleichbleibend hoher Wiederfindung. Der hohe Probendurchsatz wird weiter unterstützt durch die kurze chromatographische Laufzeit von 17 min pro Ionisationsmodus. Die Auswertung der Ergebnisse ist der heikelste und zeitintensivste Schritt bei der Entwicklung und Anwendung von Screening-Methoden, deshalb wurde der Arbeitsablauf zur univariaten Analyse durch Entwicklung von R Skripten vereinfacht und beschleunigt.
Die Qualität und Reproduzierbarkeit der Ergebnisse sind essenziell. Aus diesem Grund wurde die Qualität der entwickelten Methode, angelehnt an den strikten Vorgaben der FDA und EMA zur Validierung von quantitativen Methoden, sichergestellt, obwohl eine Methodenüberprüfung im Bereich von untargeted Methoden nicht verbreitet ist. Die Reproduzierbarkeit der relativen Lipidkonzentrationen konnte z.B. durch die Messung von Kontrollplasmaproben über einen Zeitraum von 10 Monaten gezeigt werden. Außerdem wurde die Linearität der Verdünnung von Plasmaproben bestätigt und eine Verschleppung in darauffolgende Proben ausgeschlossen. Die Stabilität der Proben muss in jeder Messphase inklusive der Präanalytik durch geeignete Untersuchungen und Maßnahmen sichergestellt werden. Anhand einer Studie zur präanalytischen Stabilität humaner Blutproben konnte ein Protokoll zur Probennahme und -vorbereitung für weitere klinische Studien erarbeitet werden. Die Stabilität des Lipidoms in Vollblut und Plasma konnte durch den Einsatz von Natriumfluorid/Citrat als Antikoagulans verbessert werden. Auch die Stabilität der Proben während der Lipidextraktion und Messung konnte gezeigt werden. Es wurden 16 verschiedene Probenarten analysiert, darunter Plasmaproben, verschiedene Mausgewebe und Zellpellets.
Mit der entwickelten Methode wurden die Unterschiede im Lipidprofil im Plasma und Gewebe von Mäusen mit einer akuten Entzündung durch LPS bzw. Zymosan-Injektion aufgedeckt. Dabei wurden die Ether-Phosphatidylcholine als potenzielle Entzündungsmarker identifiziert. Die entwickelte Methode wurde außerdem erfolgreich im Rahmen anderer Arbeiten für die Untersuchung verschiedener Erkrankungen angewendet.
In der vorliegenden Arbeit wird demnach eine schnelle, reproduzierbare und vor allem selektive LC-MS-Screening-Methode vorgestellt, die Veränderungen des Lipidstoffwechsels aufdecken und potenzielle Biomarker identifizieren kann.
Hahnefeld, Lisa Katharina ; Gruber, Lisa ; Schömel, Nina ; Fischer, Caroline ; Mattjus, Peter ; Gurke, Robert ; Beretta, Martina ; Ferreirós Bouzas, Nerea ; Geisslinger, Gerd ; Wegner, Marthe-Susanna
Identifying co-expression of lipid species is challenging, but indispensable to identify novel therapeutic targets for breast cancer treatment. Lipid metabolism is often dysregulated in cancer cells, and changes in lipid metabolism affect cellular processes such as proliferation, autophagy, and tumor development. In addition to mRNA analysis of sphingolipid metabolizing enzymes, we performed liquid chromatography time-of-flight mass spectrometry analysis in three breast cancer cell lines. These breast cancer cell lines differ in estrogen receptor and G-protein coupled estrogen receptor 1 status. Our data show that sphingolipids and non-sphingolipids are strongly increased in SKBr3 cells. SKBr3 cells are estrogen receptor negative and G-protein coupled estrogen receptor 1 positive. Treatment with G15, a G-protein coupled estrogen receptor 1 antagonist, abolishes the effect of increased sphingolipid and non-sphingolipid levels in SKBr3 cells. In particular, ether lipids are expressed at much higher levels in cancer compared to normal cells and are strongly increased in SKBr3 cells. Our analysis reveals that this is accompanied by increased sphingolipid levels such as ceramide, sphingadiene-ceramide and sphingomyelin. This shows the importance of focusing on more than one lipid class when investigating molecular mechanisms in breast cancer cells. Our analysis allows unbiased screening for different lipid classes leading to identification of co-expression patterns of lipids in the context of breast cancer. Co-expression of different lipid classes could influence tumorigenic potential of breast cancer cells. Identification of co-regulated lipid species is important to achieve improved breast cancer treatment outcome.
Hailu, Teweldemedhn Gebretinsae ; D’Alvise, Paul ; Tofilski, Adam ; Fuchs, Stefan ; Greiling, Jürgen ; Rosenkranz, Peter ; Hasselmann, Martin
Traditional beekeeping has been playing important socio-economic roles in Ethiopia for millennia. The country is situated in northeast Africa, where ranges of major evolutionary lineages of Apis mellifera adjoin. However, studies on the classification and distribution of subspecies and lineages of honey bees in the country are partly inconsistent, either proposing multiple subspecies and lineages or a unique A. m. simensis. This study was conducted with the aim of elucidating Ethiopian honey bees in reference to African subspecies and major global lineages using wing geometric morphometrics and COI-COII mitochondrial DNA analyses. For this purpose, 660 worker bees were collected from 66 colonies representing highland, midland, and lowland zones in different locations. Both methods indicated that the samples from this study form a distinct cluster together with A. m. simensis reference. In addition, forewing venation patterns showed that most of the Ethiopian samples are separate from all reference subspecies, except A. m. simensis. Analysis of COI-COII sequences revealed five DraI haplotypes (Y2, Y1, A1, and O5’), of which one was new denoted as Y3. Moreover, centroid size strongly associated with elevation. In conclusion, the results supported that Ethiopian honey bees are distinct both at lineage and subspecies levels; however, there is an indication of lineage O in the north.
Fifty years ago, Zajonc, Heingartner, and Herman (1969) conducted a famous experiment on social enhancement and inhibition of performance in cockroaches. A moderating effect of task difficulty on the effect of the presence of an audience, as revealed by impaired performance in complex tasks and enhanced performance in simple tasks, was presented as the major conclusion of this research. However, the researchers did not test this interaction statistically. We conducted a preregistered direct replication using a 2 (audience: present vs. absent) × 2 (task difficulty: runway vs. maze) between-subjects design. Results revealed main effects for task difficulty, with faster running times in the runway than the maze, and for audience, with slower running times when the audience was present than when it was absent. There was no interaction between the presence of an audience and task difficulty. Although we replicated the social-inhibition effect, there was no evidence for a social-facilitation effect.
This paper studies a household’s optimal demand for a reverse mortgage. These contracts allow homeowners to tap their home equity to finance consumption needs. In stylized frameworks, we show that the decision to enter a reverse mortgage is mainly driven by the dierential between the aggregate appreciation of the house price and principal limiting factor on the one hand and the funding costs of a household on the other hand. We also study a rich life-cycle model that can explain the low demand for reverse mortgages as observed in US data. In this model, we analyze the optimal response of a household that is confronted with a health shock or financial disaster. If an agent suers from an unexpected health shock, she reduces the risky portfolio share and is more likely to enter a reverse mortgage. On the other hand, if there is a large drop in the stock market, she keeps the risky portfolio share almost constant by buying additional shares of stock. Besides, the probability to take out a reverse mortgage is hardly aected.
In welchen Situationen steht ein Tier unter Stress und wie beeinflusst Stress dessen Wohlbefinden? Dies sind die Kernfragen, mit denen Zoos konfrontiert sind, wenn es darum geht, den Bedürfnissen ihrer Tiere gerecht zu werden. Die Beantwortung dieser Fragen ist jedoch angesichts der großen individuellen Variabilität des Inputs, der Stress hervorrufen kann,und des Outputs, der das Wohlbefinden bestimmt, eine Herausforderung. Um diese Herausforderung zu meistern, brauchen Zoos Kenntnisse darüber, welche Haltungsbedingungen und Managementsituationen Verhaltens-, physiologische oder emotionale Veränderungen hervorrufen, sowohl positive als auch negative. Dies trifft insbesondere auf Arten zu, die aufgrund ihrer Biologie und des großen öffentlichen Interesses große Anforderungen an das Management in Menschenobhut stellen, wie den Afrikanischen Elefanten. Die vorliegende Arbeit hatte daher das Ziel, unter Berücksichtigung der individuellen Variation die Auswirkungen bestimmter Managementsituationen auf physiologischen Stress und das Wohlbefinden der Tiere zu evaluieren.
Für diese Arbeit wurden zehn Afrikanische Elefanten aus drei Zoos im Rahmen eines Experiments in 2016 und 2017 mehrmals untersucht. Dieses Experiment umfasste zum einen die Messung von physiologischem Stress auf der Basis der Konzentration des „Stresshormons“ Cortisol im Speichel der Elefanten. Zu diesem Zweck wurden an bestimmten Tagen und zu folgenden Zeitpunkten Speichelproben entnommen: morgens, nachmittags vor und mehrmals nach einer von zwei Managementsituationen (positives Verstärkungstraining [PRT] und neuartiges Enrichmentobjekt [NOV]). Zum anderen diente die Exposition gegenüber dem neuartigen Enrichmentobjekt als sogenannter Novel Object Test. Dieser Standardtest der Persönlichkeitsforschung bei Tieren deckte bei anderen Arten konsistente Verhaltensunterschiede zwischen Individuen auf. Um zu untersuchen, ob dies auch auf Afrikanische Elefanten zutrifft, wurden die individuellen Verhaltensreaktionen auf das neuartige Objekt aufgezeichnet. Darüber hinaus wurden unabhängig von dem Experiment vor und nach einem Transport jeweils morgens und nachmittags Speichelproben von dem transferierten Tier und von zwei Tieren im Bestimmungszoo gesammelt, um den Effekt dieses potenziellen Stressors auf die individuellen Cortisolspiegel zu untersuchen.
Publikation A zeigt, dass die Elefanten unter den Bedingungen des Routinemanagements (das heißt dem routinemäßigen Tagesablauf der Tierpflege) am Morgen signifikant höhere Cortisolwerte im Speichel aufwiesen als am Nachmittag. Diese diurnale Variation der Cortisolsekretion ist typisch für tagaktive Arten und wurde daher auch für die untersuchten Elefanten erwartet. Unter Stressbedingungen wurde weder ein signifikanter Unterschied zwischen den Cortisolspiegeln vor und nach dem Transport noch zwischen den Cortisolwerten am Morgen und am Nachmittag festgestellt. Der prozentuale Unterschied zwischen dem morgendlichen und nachmittäglichen Cortisolspiegel war jedoch beim transferierten Tier nach dem Transport wesentlich geringer als vor dem Transport, was möglicherweise auf eine Stressreaktion auf den Transport und die Eingewöhnung im neuen Zoo hindeutet. Darüber hinaus zeigten sich deutliche Cortisolanstiege unmittelbar nach der ersten Zusammenführung des transferierten Tiers mit dem Bullen im neuen Zoo. Dieses Ergebnis demonstriert zum einen, dass Cortisol physiologischen Stress widerspiegelt. Zum anderen zeigt es die Notwendigkeit, zeitnah nach einem Stressor Speichelproben zu entnehmen, was nach dem Transport nicht möglich war.
Die Studie in Manuskript B zeigt unterschiedliche durchschnittliche Zeitverläufe der Cortisolantworten im Speichel auf die Managementsituationen PRT und NOV. PRT könnte aufgrund des beobachteten cortisolsenkenden und damit potenziell stresspuffernden Effekts förderlich für das Wohlbefinden sein. NOV induzierte im Mittel eine moderate, kurzfristige Cortisolantwort. Dies deutet darauf hin, dass die Tiere geringem physiologischem Stress ausgesetzt waren, mit dem sie jedoch erfolgreich umgehen konnten. Außerdem bestand eine bemerkenswerte individuelle Variation in den Cortisolverläufen in derselben Situation. Die Unterschiede im Cortisolspiegel zwischen den Tieren hingen mit dem Alter (bei NOV) und dem Zoo (bei PRT) zusammen. Der Effekt des Geschlechts und des Haltungssystems auf den Cortisolspiegel war hingegen variabel. Die Ergebnisse der Studie zeigen, dass die individuelle Variation der Cortisolsekretion unbedingt berücksichtigt werden muss, um physiologischen Stress zuverlässig zu erkennen.
Die Studie in Manuskript C ergab, dass sich die untersuchten Tiere im Novel Object Test konsistent in ihrem Verhalten gegenüber einem neuartigen Objekt unterschieden. Dieses Ergebnis zeigt, dass der Novel Object Test auch bei Elefanten genutzt werden kann, um die Persönlichkeit der Tiere zu untersuchen...
The present study assessed the diurnal variation in salivary cortisol in captive African elephants during routine management (baseline) and in relation to a potential stressor (translocation) to evaluate to what extent acute stress may affect diurnal cortisol patterns. Under baseline conditions, we collected morning and afternoon saliva samples of 10 animals (three zoos) on different days in two study periods (n = 3–10 per animal, daytime and period). Under stress conditions, we sampled the transported cow (newcomer) and the two cows of the destination zoo before and after the transport in the morning and afternoon (n = 3–9 per animal, daytime and transport phase), as well as after the first introduction of the newcomer to the bull (n = 1 per animal). Cortisol was measured in unextracted samples by enzyme immunoassay. Under baseline conditions, we observed the expected diurnal variation with higher cortisol levels in the morning than in the afternoon. Under stress conditions, neither a significant difference between pre‐ and posttransport, nor between morning and afternoon levels was found. The percentage difference between morning and afternoon cortisol after the transport, however, was remarkably lower than before the transport in the newcomer potentially indicating a stress response to familiarization. Saliva samples taken immediately after the introduction of the newcomer to the bull revealed a marked cortisol increase. Our findings indicate that stressors may disturb the diurnal cortisol rhythm. Furthermore, provided that samples can be collected promptly, salivary cortisol is a useful minimally invasive measure of physiological stress in the African elephant.
Understanding the hadron spectrum is one of the primary goals of non-perturbative QCD. Many predictions have experimentally been confirmed, others still remain under experimental investigation. Of particular interest is how gluonic excitations give rise to states with constituent glue. One class of such states are hybrid mesons that are predicted by theoretical models and Lattice QCD calculations. Searching for and understanding the nature of these states is a primary physics goal of the GlueX experiment at the CEBAF accelerator at Jefferson Lab. A search for a JPC = 1−− hybrid meson candidate, the Y(2175), in φ(1020)π+π+ and φ(1020)f0(980) channels in photoproduction on a proton target has been conducted. A first measurement of non-resonant φ(1020)π+π+ and φ(1020)f0(980) total cross sections in photoproduction has been performed. An upper limit on the resonance production cross section for the Y (2175) → φ(1020)π+π+ and Y (2175) → φ(1020)f0(980) channels are estimated. Since the analysis essentially depends on the quality of the charged kaon identification, also an optimization of particle identification through an improvement of the energy loss estimation in the central drift chamber by a truncated mean method has been investigated.
This thesis presents research which spans three conference papers and one manuscript which has not yet been submitted for peer review.
The topic of 1 is the inherent complexity of maintaining perfect height in B-trees. We consider the setting in which a B-tree of optimal height contains n = (1−ϵ)N elements where N is the number of elements in full B-tree of the same height (the capacity of the tree). We show that the rebalancing cost when updating the tree—while maintaining optimal height—depends on ϵ. Specifically, our analysis gives a lower bound for the rebalancing cost of Ω(1/(ϵB)). We then describe a rebalancing algorithm which has an amortized rebalancing cost with an almost matching upper bound of O(1/(ϵB)⋅log²(min{1/ϵ,B})). We additionally describe a scheme utilizing this algorithm which, given a rebalancing budget f(n), maintains optimal height for decreasing ϵ until the cost exceeds the
budget at which time it maintains optimal height plus one. Given a rebalancing budget of Θ(logn), this scheme maintains optimal height for all but a vanishing fraction of sizes in the intervals between tree capacities.
Manuscript 2 presents empirical analysis of practical randomized external-memory algorithms for computing the connected components of graphs. The best known theoretical results for this problem are essentially all derived from results for minimum spanning tree algorithms. In the realm of randomized external-memory MST algorithms, the best asymptotic result has I/O-complexity O(sort(|E|)) in expectation while an empirically studied practical algorithm has a bound of O(sort(|E|)⋅log(|V|/M)). We implement and evaluate an algorithm for connected components with expected I/O-complexity O(sort(|E|))—a simplification of the MST
algorithm with this asymptotic cost, we show that this approach may also yield good results in practice.
In paper 3, we present a novel approach to simulating large-scale population protocol models. Naive simulation of N interactions of a population protocol with n agents and m states requires Θ(nlogm) bits of memory and Θ(N) time. For
very large n, this is prohibitive both in memory consumption and time, as interesting protocols will typically require N > n interactions for convergence. We describe a histogram-based simulation framework which requires Θ(mlogn) bits of memory instead—an improvement as it is typically the case that
n ≫ m. We analyze, implement, and compare a number of different data structures to perform correct agent sampling in this regime. For this purpose, we develop dynamic alias tables which allow sampling an interaction in expected amortized
constant time. We then show how to use sampling techniques to process agent interactions in batches, giving a simulation approach which uses subconstant time per interaction under reasonable assumptions.
With paper 4, we introduce the new model of fragile complexity for comparison-based algorithms. Within this model, we analyze classical comparison-based problems such as finding the minimum value of a set, selection (or finding the median), and sorting. We prove a number of lower and upper bounds and in particular, we give a number of randomized results which describe trade-offs not achievable by deterministic algorithms.
Sprachpotenziale stärken : das Projekt Herkunftssprachen im Sprachenzentrum der Goethe-Universität
(2020)
Computational estimation is an important skill in everyday life as well as in educational contexts. In the last decades, research has found that children use several strategies in computational estimation and that children’s strategy use depends on different parameters. Still, little is known about the underlying cognitive processes. In the present work, we addressed this issue by investigating (1) the influence of individual differences in children’s executive functions on their strategy use and (2) the influence of varying specific task and problem characteristics that are discussed to involve different cognitive processes.
In four studies, we asked third and fourth graders to solve computational estimation tasks by rounding the summands. Study 1 addressed the influence of working memory updating. The study found that efficient updating contributed to children’s strategy use and moderated relations with problem characteristics. A deliberate feature of Study 1 was to restrict participants’ strategy choice to the rounding-down and rounding-up strategies. Study 2 in turn investigated children’s strategy use when mixed-rounding was allowed. Results indicated that children did not consider unit digits of both operands jointly. Also, no influence of executive functions could be found. Consequently, in Study 3, children’s strategy selection when they could choose between three versus only two strategies was contrasted and the role of working memory updating was investigated. Indeed, children chose the best available strategy more often when three strategies were available. Importantly, relative strategy selection performance differed with children’s updating capacities.
Finally, Study 4 addressed another task variation that is important in everyday life and educational contexts. That is, presentation duration and modality were varied. Data showed that a permanent, written format was most beneficial for children’s strategy use and that children’s updating moderated presentation effects.
In sum, the results of the present work could shed some light onto cognitive processes in children’s strategy use in computational estimation. Specifically working memory updating
seems to contribute to third and fourth graders strategy use. Interpreting interactions with different task variations, updating most likely influences associative processes, long term memory consolidation and retrieval as well as encoding and calculation processes.
Though the range of invariance in recognition of novel objects is a basic aspect of human vision, its characterization has remained surprisingly elusive. Here we report tolerance to scale and position changes in one-shot learning by measuring recognition accuracy of Korean letters presented in a flash to non-Korean subjects who had no previous experience with Korean letters. We found that humans have significant scale-invariance after only a single exposure to a novel object. The range of translation-invariance is limited, depending on the size and position of presented objects. To understand the underlying brain computation associated with the invariance properties, we compared experimental data with computational modeling results. Our results suggest that to explain invariant recognition of objects by humans, neural network models should explicitly incorporate built-in scale-invariance, by encoding different scale channels as well as eccentricity-dependent representations captured by neurons’ receptive field sizes and sampling density that change with eccentricity. Our psychophysical experiments and related simulations strongly suggest that the human visual system uses a computational strategy that differs in some key aspects from current deep learning architectures, being more data efficient and relying more critically on eye-movements.
High-quality single crystals of the unconventional superconductor NdFeAsO1 − xFx were grown. We developed a new optimized flux technique to overcome the difficulties in single-crystal growth and the sample quality limitations of NdFeAsO1 − xFx. The normal state of the F-doped samples exhibits simple metallic behavior upon cooling down from room temperature, followed by a sharp superconducting transition. The values of residual resistivity ratio (RRR) is 3.2, 6.4, and 10.3 for x = 0.1, 0.15, and 0.2, respectively. Both the large RRR and the narrow superconducting transition signpost the high quality of the crystals. We have examined the in- and out-of-plane lower critical fields, and the field at which vortices penetrate the sample of NdFeAsO1 − xFx (x = 0.1). The anisotropy ratio [γHc1 (0)] increased slightly with increasing temperature from 0.8 Tc to Tc. The temperature dependence of the first vortex penetration field was obtained under the static magnetic field, H, parallel to the c- and ab- axis, and pronounced changes in the Hc1(T) curvature were observed, which are attributed to the multi-band superconductivity.
Hannig, Jennifer ; Schäfer, Hendrik ; Ackermann, Jörg ; Hebel, Marie ; Schäfer, Tim ; Döring, Claudia ; Hartmann, Sylvia ; Hansmann, Martin-Leo ; Koch, Ina
In pathology, tissue images are evaluated using a light microscope, relying on the expertise and experience of pathologists. There is a great need for computational methods to quantify and standardize histological observations. Computational quantification methods become more and more essential to evaluate tissue images. In particular, the distribution of tumor cells and their microenvironment are of special interest. Here, we systematically investigated tumor cell properties and their spatial neighborhood relations by a new application of statistical analysis to whole slide images of Hodgkin lymphoma, a tumor arising in lymph nodes, and inflammation of lymph nodes called lymphadenitis. We considered properties of more than 400, 000 immunohistochemically stained, CD30-positive cells in 35 whole slide images of tissue sections from subtypes of the classical Hodgkin lymphoma, nodular sclerosis and mixed cellularity, as well as from lymphadenitis. We found that cells of specific morphology exhibited significant favored and unfavored spatial neighborhood relations of cells in dependence of their morphology. This information is important to evaluate differences between Hodgkin lymph nodes infiltrated by tumor cells (Hodgkin lymphoma) and inflamed lymph nodes, concerning the neighborhood relations of cells and the sizes of cells. The quantification of neighborhood relations revealed new insights of relations of CD30-positive cells in different diagnosis cases. The approach is general and can easily be applied to whole slide image analysis of other tumor types.