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Background: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients. Pre-selection of those patients using a registry could facilitate the process of eligibility testing and increase the number of identified patients. One aim with the PRAEGNANT registry (NCT02338167) is to identify patients for therapies based on clinical and molecular data. Here, we report eligibility testing for the SHERBOC trial using the German PRAEGNANT registry.
Methods:Heregulin (HRG) has been reported to identify patients with better responses to therapy with the anti-HER3 monoclonal antibody seribantumab (MM-121). The SHERBOC trial investigated adding seribantumab (MM-121) to standard therapy in patients with advanced HER2-negative, hormone receptor–positive (HR-positive) breast cancer and HRG overexpression. The PRAEGNANT registry was used for identification and tumor testing, helping to link potential HRG positive patients to the trial. Patients enrolled in PRAEGNANT have invasive and metastatic or locally advanced, inoperable breast cancer. Patients eligible for SHERBOC were identified by using the registry. Study aims were to describe the HRG positivity rate, screening procedures, and patient characteristics associated with inclusion and exclusion criteria.
Results: Among 2769 unselected advanced breast cancer patients, 650 were HER2-negative, HR-positive and currently receiving first- or second-line treatment, thus potentially eligible for SHERBOC at the end of current treatment; 125 patients also met further clinical eligibility criteria (e.g. menopausal status, ECOG). In the first/second treatment lines, patients selected for SHERBOC based on further eligibility criteria had a more favorable prognosis than those not selected. HRG status was tested in 38 patients, 14 of whom (36.8%) proved to be HRG-positive.
Conclusion: Using a real-world breast cancer registry allowed identification of potentially eligible patients for SHERBOC focusing on patients with HER3 overexpressing, HR-positive, HER2-negative metastatic breast cancer. This approach may provide insights into differences between patients eligible or non-eligible for clinical trials.
Trial registration: Clinicaltrials, NCT02338167, Registered 14 January 2015 - retrospectively registered.
Background: Meta-analysis of observational studies concluded that soft drinks may increase the risk of depression, while high consumption of coffee and tea may reduce the risk. Objectives were to explore the associations between the consumption of soft drinks, coffee or tea and: (1) a history of major depressive disorder (MDD) and (2) the severity of depressive symptoms clusters (mood, cognitive and somatic/vegetative symptoms). Methods: Cross-sectional and longitudinal analysis based on baseline and 12-month-follow-up data collected from four countries participating in the European MooDFOOD prevention trial. In total, 941 overweight adults with subsyndromal depressive symptoms aged 18 to 75 years were analyzed. History of MDD, depressive symptoms and beverages intake were assessed. Results: Sugar-sweetened soft drinks were positively related to MDD history rates whereas soft drinks with non-nutritive sweeteners were inversely related for the high vs. low categories of intake. Longitudinal analysis showed no significant associations between beverages and mood, cognitive and somatic/vegetative clusters. Conclusion: Our findings point toward a relationship between soft drinks and past MDD diagnoses depending on how they are sweetened while we found no association with coffee and tea. No significant effects were found between any studied beverages and the depressive symptoms clusters in a sample of overweight adults.
Trypanosoma cruzi, the causative agent of Chagas disease, colonizes the gut of triatomine insects, including Rhodnius prolixus. It is believed that this colonization upsets the microbiota that are normally present, presumably switching the environment to one more favorable for parasite survival. It was previously thought that one particular bacterium, Rhodococcus rhodnii, was essential for insect survival due to its ability to produce vital B-complex vitamins. However, these bacteria are not always identified in great abundance in studies on R. prolixus microbiota. Here we sequenced the microbiota of the insect anterior midgut using shotgun metagenomic sequencing in order to obtain a high-resolution snapshot of the microbes inside at two different time points and under two conditions; in the presence or absence of parasite and immediately following infection, or three days post-infection. We identify a total of 217 metagenomic bins, and recovered one metagenome-assembled genome, which we placed in the genus Dickeya. We show that, despite Rhodococcus being present, it is not the only microbe capable of synthesizing B-complex vitamins, with the genes required for biosynthesis present in a number of different microbes. This work helps to gain a new insight into the microbial ecology of R. prolixus.
Bioaerosols are considered to play a relevant role in atmospheric processes, but their sources, properties and spatiotemporal distribution in the atmosphere are not yet well characterized. In the Amazon Basin, primary biological aerosol particles (PBAP) account for a large fraction of coarse particulate matter, and fungal spores are among the most abundant PBAP there as well as in other vegetated continental regions. furthermore, PBAP could also be important ice nuclei in Amazonia. Measurement data on the release of fungal spores under natural conditions, however, are sparse. Here we present an experimental approach to analyze and quantify the spore release from fungi and other spore producing organisms under natural and laboratory conditions. For measurements under natural conditions, the samples were kept in their natural environment and a setup was developed to estimate the spore release numbers and sizes together with the microclimatic factors temperature and air humidity, as well as the mesoclimatic parameters net radiation, rain, and fog occurrence. For experiments in the laboratory, we developed a cuvette to assess the particle size and number of newly released fungal spores under controlled conditions, simultaneously measuring temperature and relative humidity inside the cuvette. Both approaches were combined with bioaerosol sampling techniques to characterize the released particles by microscopic methods. For fruiting bodies of the basidiomycetous species, Rigidoporus microporus, the model species for which these techniques were tested, the highest frequency of spore release occurred in the range of 62 and 96 % relative humidity. The results obtained for this model species reveal characteristic spore release patterns linked to environmental or experimental conditions, indicating that the moisture status of the sample may be a regulating factor, while temperature and light seem to play a minor role for this species. The presented approach enables systematic studies aimed at the quantification and validation of spore emission rates and inventories, which can be applied to a regional mapping of cryptogamic organisms under given environmental conditions.
Bioaerosols are considered to play a relevant role in atmospheric processes, but their sources, properties, and spatiotemporal distribution in the atmosphere are not yet well characterized. In the Amazon Basin, primary biological aerosol particles (PBAPs) account for a large fraction of coarse particulate matter, and fungal spores are among the most abundant PBAPs in this area as well as in other vegetated continental regions. Furthermore, PBAPs could also be important ice nuclei in Amazonia. Measurement data on the release of fungal spores under natural conditions, however, are sparse. Here we present an experimental approach to analyze and quantify the spore release from fungi and other spore-producing organisms under natural and laboratory conditions. For measurements under natural conditions, the samples were kept in their natural environment and a setup was developed to estimate the spore release numbers and sizes as well as the microclimatic factors temperature and air humidity in parallel to the mesoclimatic parameters net radiation, rain, and fog occurrence. For experiments in the laboratory, we developed a cuvette to assess the particle size and number of newly released fungal spores under controlled conditions, simultaneously measuring temperature and relative humidity inside the cuvette. Both approaches were combined with bioaerosol sampling techniques to characterize the released particles using microscopic methods. For fruiting bodies of the basidiomycetous species, Rigidoporus microporus, the model species for which these techniques were tested, the highest frequency of spore release occurred in the range from 62 % to 96 % relative humidity. The results obtained for this model species reveal characteristic spore release patterns linked to environmental or experimental conditions, indicating that the moisture status of the sample may be a regulating factor, whereas temperature and light seem to play a minor role for this species. The presented approach enables systematic studies aimed at the quantification and validation of spore emission rates and inventories, which can be applied to a regional mapping of cryptogamic organisms under given environmental conditions.
La risa es uno de los temas menos estudiados en la obra de Walter Benjamin; sin embargo, constituye una de las claves para la comprensión de lo que el crítico alemán consideró que podría ser una politización del arte. En este artículo tratamos de desgranar el lugar de la risa en la teoría estética y política de Benjamin a partir de su conferencia «El autor como productor». Desde ese punto nos proponemos introducir su lectura de Bertolt Brecht, así como su polémica con Theodor W. Adorno.
В статті проаналізовано основні ідеї представників Франкфуртської школи, а саме: Т. Адорно, М. Хоркхаймер, Г. Маркузе, Е. Фромм. Опираючись на основні дослідження та основоположні філософські праці представників Франкфуртської школи, зроблена спроба виокремити основні причини становлення неототалітаризму, та тоталітарних режимів у ХХ столітті. Встановлена взаємозалежність між Просвітницькою діяльністю та міфологізацією свідомості; визначена роль культури у цьому процесі. Окреслено роль ідеологічної системи, як однієї з форм соціальної міфології. Встановлена закономірність між «щасливою свідомістю» суспільства споживання і ефективним укоріненням міфів та ідеологічних систем у масову свідомість суспільства ХХ ст. Актуальність статті зумовлена тим, що необхідність критичного осмислення становлення культури тоталітарних країн сьогодні стає очевидною. Усвідомлення того, що суспільна свідомість пострадянських країн досі керується міфологемами, що були створені та впроваджені тоталітарною культурою, змушує нас серйозно вивчати проблематику міфологізації свідомості та ідеологічного впливу. Тому позбавлення від упереджень та перехід до нового витка демократичної свідомості неможливий, без вивчення основ становлення масового суспільства та функції культури в ньому. Більше того, без виявлення чинників, що зумовили конструювання західної цивілізації, неможливе не тільки рішення глобальних проблем сучасності, але й сам перехід на якісно інший виток соціально-культурного розвитку.
L’école de Frankfort abandonne progressivement les thèses de la philosophie de l’Histoire, dont l’acceptation fournissait une espèce de fondement pour la théorie critique, dans la mesure où l’on pouvait croire aux contenus émancipateurs de la raison inclus au sein même des idées de la société bourgeoise. Nous essayerons de montrer cequi est oublié dans les thèses de la philosophie de l’Histoire à partir de la dialectique du maître et de l’esclave de Hegel, et donc, pourquoi de telles thèses se sont montrées insuffisantes. Enfin, nous chercherons à démontrer que la figure théorique opposée aux thèses de la philosophie de l’Histoire se retrouve dans Über den Begriff der Geschichte de Benjamin. De plus, la récupération d’un tel fondement oublié dans les thèses de la philosophie de l’Histoire détermine, vraisemblablement, la considération morale de la théorie critique habermasienne.
O Objetivo deste artigo consiste em apresentar fundamentos da proposta epistemológica de Jürgen Habermas, identificados em obras precedentes à sua Teoria do agir comunicativo. A partir de Teoria analítica da ciência e dialética será explorada a proposta do autor, tendo percorrido antecipadamente pela querela entre Popper e Adorno; posteriormente busca-se analisar como Habermas, em debate com seus contemporâneos, retrata sua proposta em Técnica e ciência como ideologia, considerado um marco para a Escola de Frankfurt.
Nos Mandamentos, Deus proíbe aos homens tanto a feitura de imagens quanto a pronúncia em vão de Seu nome. Há, portanto, limites rígidos entre as esferas do sagrado e do humano. Este artigo examinará paralelos e divergências entre os pensamentos de dois autores que abordaram essa questão a partir de escolas de pensamento distintas: o filósofo neomarxista judeu Theodor Adorno e o teólogo luterano Eberhard Jüngel.
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.
Mannov román Doktor Faustus. Das Leben des deutschen Tonsetzers Adrian Leverkühn erzählt von seinem Freunde (Doktor Faustus. Život nemeckého skladateľa Adriana Leverkühna rozprávaný jeho priateľom, 1947) je jeden z najznámejších literárnych diel 20. storočia. Základom jeho vzniku bolo stretnutie T. Manna s filozofom a muzikológom T. W. Adornom v americkom exile počas 2. svetovej vojny. Mannov román je poetizáciou a narativizáciou, či literarizáciou a fikcionalizáciou Adornovej hudobnej teórie a estetiky ako ich nachádzame v rôznych Adornových prácach, najmä v knihe Philosophie der neuen Musik (1949).
Mannov román Doktor Faustus. Das Leben des deutschen Tonsetzers Adrian Leverkühn erzählt von seinem Freunde (Doktor Faustus. Život nemeckého skladateľa Adriana Leverkühna rozprávaný jeho priateľom, 1947) vznikol v úzkej spolupráci spisovateľa Th. Manna a Th. W. Adorna. Adorno bol Mannovi nielen odborným konzultantom v otázkach dejín hudby, hudobnej estetiky a hudobnej teórie, ale bol do istej miery aj spoluautorom románu: hudobné analýzy a charakteristiky skladieb ktoré sa viažu na fiktívne románové postavy hudobníkov Kretzschmara a Leverkühna, ako aj na Mefista, pochádzajú od Adorna. Špecifickým problémom románu v tomto zmysle je „fiktívna hudba“. Adorno vytvoril fiktívne hudobné skladby fiktívneho skladateľa Leverkühna, podľa Mannových predstáv. Východiskom tejto literárnej fikcie boli skladby A. Schönberga, I. Stravinského a G. Mahlera. Mannove/Adornove fiktívne skladby sú predmetom pozornosti v analýzach Mannovho románu, a sú témou aj tejto štúdie.
Štúdia Fiktívne hudobné kompozície Th. W. Adorna v románe Thomasa Manna „Doktor Faustus“vychádza z autorovej staršej štúdie Theodor W. Adorno a román Th. Manna ´Doktor Faustus´. In: Slovenské pohľady, č. 7-8, 2013, roč. 129, s. 136-147.
Pokračujúc v zámere predchádzajúceho príspevku tento text otvára znova problém recepcie Kantovho vymedzenia kategórie vznešeného. Variácie, ktoré vykonávajú Schopenhauer, Nietzsche a Adorno predstavujú inovatívne prístupy. Premostenie dejín tejto estetickej kategórie do 20.storočia v myslení sledovaných autorov predstavuje funkčnosť vznešeného v premenách umeleckého a estetického diskurzu a nabáda k jeho aktualizovaniu v súčasnosti.
In the1960s, texts by the prominent German philosopher and musicologist Theodor W. Adorno were translated into the Czech and Slovak language. This was only possible due to the more relaxed social and political atmosphere of those years. The translated essays were published in professionally-oriented periodicals. This paper is aimed to map and evaluate the reception of Adorno’s translatedworks in Czechoslovakia. Although these texts embraced above all Adorno’s work in the sociology of philosophy, aesthetics of literature and musicology, this paper is mainly focused on Adorno’s musicological texts. Albeit mostly regarded as an original and extremely versatile author in Czechoslovakia, Adorno was also criticised on the background of Marxist-Leninist philosophy. In order to evaluate the reception of Adorno’s ideas in the Czech and Slovak environment, it is methodologically necessary to adopt a broader aesthetic-philosophical perspective that enables us to account for Adorno’s endorsement of the Marxist philosophy pursued at Frankfurt School of Philosophy.
Il saggio approfondisce l’opera di due artisti fondamentali degli ultimi decenni, ovvero Antoni Tàpies e Bill Viola. La loro produzione artistica riesce a sfuggire alla condanna che Th. W. Adorno fa di tutti quei movimenti che rimettono in questione il concetto di arte e la nozione di opera. Questi due artisti salvano lo statuto dell’arte nella società post-industriale, vale a dire in un momento in cui le trasformazioni profonde del sistema culturale rischiano di minacciare la sopravvivenza della creazione artistica, come se la razionalità estetica non potesse che abdicare davanti alla razionalità strumentale. Sono pochi i pittori che come Antoni Tàpies riescono a infondere alla materia inanimata un’irradiazione e una capacità di evocazione tanto intense, mentre per Bill Viola tutte le opere d’arte rappresentano cose invisibili e la stessa tecnologia digitale non è altro che una forma più pura per avvicinarsi a quelle realtà non fisiche e non visibili che stanno sotto alle cose visibili del mondo. La scommessa di Tàpies e Viola riguarda la sopravvivenza dell’arte nell’universo mercantile di una società sempre più amministrata e sottoposta agli imperativi economici; la loro produzione pare mirata a renderci consapevoli della nostra mortalità, offrendo immagini in grado di mettere in connessione la dimensione sensibile e quella spirituale, il visibile e l’invisibile, aprendo lo spazio a una trascendenza che sembrava completamente svanita.
The paper proposes a new understanding of the notion of “aura” as it emerges, including similarities and differences, in the aesthetic thought of Walter Benjamin and Theodor W. Adorno. In particular, the paper shows how, not only in Adorno but already in Benjamin, such a concept designates also the capacity of artwork to refers, by its own internal, to an irreducible otherness. In this perspective, in a world increasingly dominated by a tendency to homologation and mercification – with the resulting identification of art and cultural industry –, contemporary art looks like a continuous oscillation between the will to deny aura and, other times, the awareness of its necessary survival, closely related (in particular, according to Adorno) to the recognition of the need to “save” not only the appearance but also, by that very fact, the aesthetic autonomy.
In Paris, metropolis of xix century, Benjamin traces the new paradigm of modernity: the modern theatrical dimension corresponds to the artistic innovations and to the reproduction of aesthetical requests. Entfremdung and Neutralisierung are the main characters of the Ästhetisierung and they are one with the distraction as principle of reception and the conformism as principle of valuation. This is the context of the aura’s decline. The Adorno’s critical essay on the radio (1963) analyses the transformation of works of art in cultural gifts and, in particular, the loss of autonomy of the musical work of art in the radio listening. The Adorno’s remarks recognize the historical character of aura and a new possibility that it can re-emerge in a new historical dimension of the music.
Sublimity, negativity, and architecture. An essay on negative architecture through Kant to Adorno
(2015)
Architecture defines and consumes people. It exposes them to a multitude of varieties of different aesthetic engagements. Architecture becomes a lived experience. However, this lived experience is always caught in the inner workings of the social and more specifically within cultural ideology. In modern capitalism, culture pervades every aspect of our lives. It shows its presence everywhere from our own homes to the public streets. Culture is everywhere, and architecture is a tool used for both the benefit and detriment of the “culture industry”. Kant speaks of the sublime as a profound moment of reason realizing its ability to overcome its own limits. In this experience is it possible to be completely ravaged and descend into hades and melancholy? Is there a beauty in this descent? More specifically, can architecture become banal or pedestrian, uplifting or depressing? According to Theodor Adorno, our subjectivity is defined by the constant dialectical struggle between freedom and unfreedom (among other things). It is realizing our freedom in the face of our unfreedom that makes us truly able to attain some form of resistance. The sublime experience can be transformed into a spirit of revelation and beautifully allow us to in a way resist the one-dimensional tendencies of modern capitalism. Architecture, which is immersed in our societal being and contributes to many of our own subjective unfreedoms, comes to define our lives as inhabited space. When does architecture produce a sublime experience? Can architecture’s authentic “aura” stand out amongst the reproduced city and produce a sublime feeling that can be a form of resistance against the culture industry? Does Grand Central Terminal provide the key to an architecturally sublime experience? Using dialectical experience and examining the sublime feeling (in a critique of the Kantian sublime) as the key to breaking through the culture industry’s banal architectural hold on our subjectivity, this essay will examine the experience of the sublime as a key to unfolding resistance in the face of the banality of modern architecture in the city and opening our minds to the Great Refusal through the exploration of Grand Central Terminal.
Il saggio si propone di approfondire due tendenze tipiche della musica contemporanea: la prima è il Minimalismo, movimento rappresentato da musicisti come La Monte Young, Philip Glass and Steve Reich, la seconda è la rave music (come la techno), caratteristica della popular culture nell’era postmoderna. Attraverso il pensiero di Adorno, e a partire dalla sua analisi dialettica del dualismo Schönberg-Stravinskij, il saggio propone una comprensione filosofica di concetti come “ripetizione” e “trascendenza”; l’assenza dello “sviluppo” in gran parte della produzione musicale degli ultimi decenni, nella popular music quanto nella musica colta, dimostra una dispersione del soggetto e dell’individuo, smarrito all’interno di un “eterno ritorno” della struttura ritmica che può essere ricompreso nei termini di un “eterno ritorno dell’identico” e non nei termini di un “eterno ritorno della possibilità”; in quest’ottica, a venire sacrificata è anche la dimensione della trascendenza, che non a caso viene ricercata spesso nell’esotismo dei culti orientali o nel consumo di sostanze stupefacenti. L’insistenza nel Minimalismo della ripetizione come unica ed estrema categoria di riferimento e norma estetica, produrrà infatti nel corso degli ultimi anni una dicotomia apparentemente contraddittoria, ma che invece esprime la medesima matrice logica: da un lato l’invasamento edonistico del beat elettronico della musica dance elettronica, dall’altro la proposta commerciale della produzione industriale della musica pop. Non è un caso che proprio il Minimalismo sia sfociato in entrambe queste due tendenze, mostrandosi come la cifra comune originaria, traducendosi nella musica rave o nella musica rock.
An easy-to-use model to evaluate conductivities at high and middle latitudes in the height range 70–100 km is presented. It is based on electron density profiles obtained with the EISCAT VHF radar during 11 years and on the neutral atmospheric model MSIS95. The model uses solar zenith angle, geomagnetic activity and season as input parameters. It was mainly constructed to study the properties of Schumann resonances that depend on such conductivity profiles.
Theoretical accounts agree that German restrictive relative clauses (RCs) are integrated at the level of syntax as well as at the level of prosody (; , ; ; ; ) in both the default verb-final and the marked verb-second variant (referred to as iV2). Both variants are assumed to show the same prosodic pattern, i. e., prosodic integration into the main clause, and not unintegrated prosody, which would signal a sequence of two main clauses. To date strong empirical evidence for this close correspondence between prosody and syntax in RCs is missing. Findings regarding prosodic integration of verb-final RCs are not consistent, and research regarding the prosody of iV2 structures is very scarce. Using a delayed sentence-repetition task, our study investigated whether subordination is signaled by prosody in RCs in both the verb-final and the V2 variant in adults (n = 21). In addition, we asked whether young language learners (n = 23), who at the age of 3 have just started to produce embedded clauses, are already sensitive to this mapping. The adult responses showed significantly more patterns of prosodic integration than of prosodic non-integration in the V-final and the iV2 structures, with no difference between the two conditions. Notably, the child responses mirrored this adult behavior, showing significantly more patterns of prosodic integration than of prosodic non-integration in both V-final and iV2 structures. The findings regarding adults’ prosodic realizations provide novel empirical evidence for the claim that iV2 structures, just like verb-final RCs, show prosodic integration. Moreover, our study strongly suggests that subordination is signaled by prosody already by age 3 in both verb-final and V2 variants of RCs.
Three experiments investigated the interpretation and production of pronouns in German. The first two experiments probed the preferred interpretation of a pronoun in contexts containing two potential antecedents by having participants complete a sentence fragment starting either with a personal pronoun or a d-pronoun. We systematically varied three properties of the potential antecedents: syntactic function, linear position, and topicality. The results confirm a subject preference for personal pronouns. The preferred interpretation of d-pronouns cannot be captured by any of the three factors alone. Although a d-pronoun preferentially refers to the non-topic in many cases, this preference can be overridden by the other two factors, linear position and syntactic function. In order to test whether interpretive preferences follow from production biases as proposed by the Bayesian theory of Kehler et al. (2008), a third experiment had participants freely produce a continuation sentence for the contexts of the first two experiments. The results show that personal pronouns are used more often to refer to a subject than to an object, recapitulating the subject preference found for interpretation and thereby confirming the account of Kehler et al. (2008). The interpretation results for the d-pronoun likewise follow from the corresponding production data.
Este trabajo es el resultado de la investigación Capital Humano como factor de crecimiento Económico, en el cual se desarrolla una reflexión crítica sobre la teoría del Capital Humano, el abordaje se hace desde la teoría económica y el análisis tiene como referente los planteamientos de la Escuela de Frankfurt, especialmente en lo que tiene que ver con el uso desde la perspectiva de la racionalidad. Desde el punto de vista metodológico se trata de una investigación cualitativa, basada en un proceso de carácter interpretativo y comprensivo de tipo Histórico Hermenéutico, el método utilizado responde a una finalidad de descripción, interpretación, argumentación, que permitan avanzar hacia la comprensión de las temáticas estudiadas en un proceso dialéctico. Como resultado del proceso investigativo se hace un análisis de la instrumentalización de la educación, la formación, la capacidad de trabajo y el estado de salud del hombre, y aún de su propio ser, las cuales se consideran de la misma naturaleza que una maquina y quedan cosificadas al ser convertidas en mercancías comerciales que se venden en el mercado, lo que determina la posibilidad de colocarle un precio pagado en el mercado a la productividad de un tipo de trabajo determinado, a la acción del propio hombre y el desarrollo de sus capacidades superiores que deberían permitirle contribuir al logro de una sociedad mejor y una vida más digna.
O objetivo deste ensaio é argumentar em favor da frankfurtianidade de Jürgen Habermas, isto é, estudar os pontos de convergência de sua obra em relação ao projeto teórico do Instituto de Pesquisa Social de Frankfurt e, a partir dessa ênfase, apontar novas possibilidades de pesquisa no campo de Estudos Organizacionais (EO). Para isso, refletimos sobre aspectos teóricos essenciais do ensaio “Teoria tradicional e teoria crítica” (HORKHEIMER, 1975) e elaboramos uma crítica aos intérpretes que utilizam a cronologia geracional como principal critério para a compreensão de diferenças no movimento intelectual da Escola de Frankfurt. Metodologicamente, inspiramo-nos na proposta de crítica à interpretação por meio da hermenêutica filosófica (RICOEUR, 1990) e na natureza propositiva de interpretação de um ensaio teórico (MENEGHETTI, 2011). Para sustentar a proposição expressa de forma provocativa no título deste artigo, dialogamos com comentadores (BOTTOMORE, 2001; FREITAG, 2004; NOBRE, 2004; MELO, 2013), a fim de propor uma caracterização não geracional de seus membros e a proximidade de Habermas em relação ao marco fundador da Teoria Crítica. Nesse sentido, acreditamos que (a) a releitura da intenção emancipadora (HABERMAS, 2002), (b) a desconstrução da isenção do conhecimento científico (HABERMAS, 1987) e (c) a incorporação da filosofia da linguagem à crítica social frankfurtiana (HABERMAS, 2012) são contribuições importantes de sua obra à Teoria Crítica de Frankfurt. Como proposição para a área de EO, em nossas considerações finais argumentamos que a recolocação do autor no posto de genuíno teórico crítico da Escola de Frankfurt pode constituir uma nova agenda de pesquisa para o campo. Acreditamos que nosso esforço pode auxiliar pesquisadores da área de EO a compreender a obra de Habermas a partir de uma via que os afasta da armadilha de considerá-lo um teórico não crítico e/ou utópico. Sob esse enfoque, torna-se evidente sua produção intelectual politicamente engajada nos problemas sociais contemporâneos – dimensão que vem sendo negligenciada pelos pesquisadores do campo de EO no Brasil.
This essay reflects on the convergence between Jürgen Habermas’ work and the theoretical framework put forward by the Institute of Social Research in Frankfurt, arguing in favor of the characteristics of the Frankfurt school in Habermas and pointing out research possibilities in the field of Organizational Studies (OS). We discuss the essential theoretical aspects of the work by Horkheimer (1975) “Traditional and Critical Theory,” and produce a critique on the use of generational chronology as the main criterion for understanding the intellectual movement of the Frankfurt School. The methodology is based on the critique of the interpretation using the philosophical hermeneutics (RICOEUR, 1990) and observes the propositional nature of an interpretation offered in theoretical essays (MENEGUETTI, 2011). To support the provocative proposition of this work, we establish a dialogue with authors such as Bottomore (2001), Freitag (2004), Nobre (2004), and Melo (2013)) discussing a non-generational characterization of the Frankfurt School’s members and the proximity of Habermas in relation to the pioneer works on the Critical Theory. We believe that (i) the re-reading of the emancipatory purpose (HABERMAS, 2002); (ii) the deconstruction of the impartiality of the scientific knowledge (HABERMAS, 1987); (iii) and the incorporation of the philosophy of language into the Frankfurtian social criticism (HABERMAS, 2012) are important contributions of Habermas to the Frankfurt’s critical theory. As for a proposal for the field of organizational studies, this esseay concludes that recognizing Habermas as a Critical Theory scholar of the Frankfurt School may constitute a new research agenda for the field. The contribution of this essay lies in helping researchers in the field of Organizational Studies to understand Habermas’ work differently and not as a non-critical or utopian production. In this perspective, it is clear that Habermas’ intellectual production is politically engaged in contemporary social problems, which is a dimension neglected by the researchers of the field of Organizational Studies in Brazil.
Nosso objetivo neste trabalho é tentar esclarecer o mal-estar causado por algumas leituras que muitas vezes despacham a influência e a presença constante de Hegel na obra de Adorno de forma muito breve e fácil, seja a partir da perspectiva antissistêmica da filosofia adorniana, ou então, desde a perspectiva negativa que a dialética assume em seu pensamento. Nesse sentido, pretendemos expor alguns pontos fundamentais da filosofia hegeliana, em relação aos quais Adorno se coloca claramente como herdeiro. Pretendemos mostrar que o filósofo de Frankfurt pensa não somente sobre estes pontos, mas também a partir deles, i.e., superando-os.
Ao tratar de diferentes aspectos do conceito de mimese na estética de Theodor Adorno, o artigo busca evidenciar a permanência do que Adorno designou como mimese primitiva ou originária na sociedade contemporânea. A análise do conceito de idiossincrasia servirá para mostrar esta permanência e, ao mesmo tempo, o seu reforço pela indústria cultural. Como contraponto a essa faceta do conceito de mimese, trataremos da mimese nos âmbitos científico, filosófico e no que Adorno considera obra de arte autêntica.
Adorno pensou a filosofia moral em diversos momentos de sua carreira filosófica, notadamente em Minima Moralia (1951), Dialética Negativa (1966) e em seu curso publicado postumamente Probleme der Moralphilosophie (1996). Uma avaliação conjunta desses textos permite indicar a centralidade do que Adorno chamou de “dialética da moral” – entre impulso somático e racionalidade – na constituição da experiência do prático. Além disso, as reflexões sobre a moral são um momento privilegiado das análises metafilosóficas de Adorno, que identificam em boa parte da tradição filosófica ocidental sobre a moral a presença da dominação da natureza interna – processo que caberia à dialética materialista da moral criticar e ajudar a transformar.
A concepção de filosofia formulada por Adorno foi impulsionada principalmente pela sua reação crítica a sistemas com pretensões totalitárias: nazismo, stalinismo e a sociedade produtora de mercadorias. A filosofia representa um refúgio para a liberdade diante dessas estruturas: ela dá voz ao não-idêntico. A capacidade de subverter os ordenamentos conceituais e sociais é implícita ao próprio pensamento, que se articula na forma de constelações em devir. A aproximação da dialética com o materialismo, concebido enquanto primazia do objeto, fortalece a filosofia na sua potencialidade crítica, na sua proximidade com a realidade e com a liberdade. Resulta daí uma filosofia renovada, simultaneamente aberta e comprometida com a verdade. A proposta deste artigo é apresentar a interdependência desses conceitos e apontar para a relevância da concepção de filosofia que deles emerge.
O artigo analisa a crítica social de Adorno, apontando os laços entre formação, sujeito e condições sociais e os efeitos para a educação (Bildung). A despeito da tradição neo-humanista e idealista e das certezas emancipatórias, a formação mostra sua face ilusória. É justamente em relação às questões educativas que o pensamento crítico de Adorno mais revela sua atualidade e potência para mostrar os paradoxos da própria educação. De tal crítica - apesar do paradoxo - decorrem determinadas exigências expressas numa dimensão ético-política e numa dimensão estética para a experiência formativa, cuja potência pode romper com o caráter meramente adaptativo da educação.
O trabalho pretende discutir o duplo caráter das obras de arte a partir da obra de Theodor W. Adorno. Pretende-se examinar os argumentos sustentados pelo autor sobre o caráter social das obras, principalmente, no caso da música, em que se pode percebercomo o desenvolvimento do próprio material musical expressa as aporias encontradas na sociedade. Por meio de uma crítica dialética, modo pelo qual as obras de arte respondem às contradições da sociedade, colocando-se, assim, como força de resistência à reificação, quanto a influência negativa que sofrem, porexemplo, no contexto da indústria cultural. Além disso, o artigo pretende se dedicar à reflexão sobre a autonomia das obras de arte, qualidade que as mantém fechadas, desenvolvendo-se apenas segundo leis formais internas, sem que atendam a uma função social. É nesse sentido quese coloca a exigência de uma determinada forma de recepção dasobras, orientada não pela fruição, mas pela possibilidade de interpretar seu teor de verdade. Assim, a dialética presente no modo como as obras se relacionam com a sociedade torna possível concebê-las como possibilidade de crítica à realidade e de resistência à reificação.
Este artigo analisa a crítica de Adorno à ontologia de Heidegger. Para tal, utiliza como leitmotiv a interpretação heideggeriana de Kant. Procuraremos mostrar que para Adorno a edificação da ontologia fundamental a partir da filosofia de Kant é uma interpretação indevida desta. Por fim, procura apontar uma possível saída na filosofia de Adorno para o problema da necessidade de fundamentação do discurso filosófico. Tal saída passa pela constatação da importância da arte para a construção da universalidade na filosofia.
A atualidade da crítica de Adorno para as pesquisas qualitativas com bases empíricas em educação
(2018)
Neste artigo, serão apresentados dados e argumentos sobre a atualidade da crítica de Theodor W. Adorno para as pesquisas qualitativas com bases empíricas em educação, com especial ênfase à hermenêutica objetiva, desenvolvida por Ulrich Oevermann e aplicada por Andreas Gruschka às pesquisas em educação. O tema será abordado da seguinte maneira: (a) serão apontados elementos históricos e teóricos do desenvolvimento de um método de pesquisa próprio pela Teoria Crítica; (b) serão apresentados elementos caracterizadores da hermenêutica objetiva; (c) para, por fim, apresentar algumas das contribuições de Gruschka na aplicabilidade do referido método às pesquisas educacionais na Alemanha, além de algumas experiências no Brasil a partir da referida abordagem de pesquisa.
Este artigo discute o sentido pretendido por Adorno com a expressão “derradeira chance do pensamento”. Para tal, busca-se uma aproximação entre alguns elementos presentes nas seções 1 e 41 de Minima moralia, em especial: o intelectual independente e o filósofo-escritor como porta-vozes da crítica à falta de originalidade na produção filosófica.
A Teoria Crítica propõe, com Theodor Adorno, uma íntima relação entre filosofia e desenvolvimento de experiências formativas, constituindo um referencial teórico indispensável para o entendimento acerca do que é pensar filosoficamente em uma perspectiva denominada negativa. Nessa relação, a experiência e racionalidade estética demarcam uma nova forma de conceber a razão e seu momento na relação com a objetividade. Esse momento da razão não indica apropriação, mas remete para uma aproximação e, a partir dessa, a construção de sentido. A problemática que orienta este texto indaga sobre como os conceitos de concreto, aproximação e construção se articulam no desenvolvimento das chamadas experiências formativas. Defendemos a hipótese de que a partir da articulação desses conceitos a riqueza constitutiva da realidade passa a ser manifestada e apreendida, possibilitando, mediante a ampliação das experiências, a manifestação do novo e a construção de sentido. Essa constelação conceitual indica o desafio de considerar a objetividade para além do imediatamente dado; indica, também, o sentido que deve assumir a tensão dialética geradora da aproximação e, por último, um caminho que nos auxilia na tarefa de compreensão do pensamento crítico de Theodor Adorno.
The purpose of the text is to present an interpretation of Theodor Adorno’s critical reading of authors considered revisionists of Sigmund Freud’s psychoanalytic theory, particularly Karen Horney. We discuss critically Adorno’s favorable positioning to the Freudian conception of the individual psychic nucleus in contrast to the hasty sociologization of psychoanalysis practiced by the revisionism of Karen Horney. In the final part we try to show how the Adornian perspective ends up by making, in his own way, the same mistake of a hasty sociologization of psychoanalysis he imputed to the revisionists and advocates an theoretical emphasis on the sociological realm that seems also problematic.
Este escrito reconstruye la problematización que Wellmer hace del planteamiento adorniano sobre el hundimiento de la metafísica y su articulación con una eventual alternativa estética para, inmediatamente, explorar la propuesta integral de la tercera Escuela de Frankfurt en torno a la eticidad democrática, sustentable desde los planteamientos de Dubiel, Honneth y Wellmer, como alternativa para una superación de las aporías que Adorno y la primera Escuela de Frankfurt no logran superar, categoría que nos remite en Habermas a su noción del patriotismo constitucional donde adquiere toda su proyección política postconvencional la eticidad democrática y que concurre en la figura de una opinión pública contestataria, que tanto Habermas como Nancy Fraser han querido fundamentar, como opción contra hegemónica y potencialmente emancipatoria en las sociedades en conflicto, para finalmente articular lo anterior con el talante cosmopolita del republicanismo que enfatiza, desde Nussbaum, Bohman y de nuevo Fraser, la perspectiva transnacional que las aspiraciones emancipatorias pueden tener en un mundo global, cuyas sinergias confluyen y concretan no solo estrategias de convivencia democrática nacionales e internacionales sino además, a través de las mismas, la superación concreta —no meramente ética o estética— de fenómenos de autoritarismo político y alienación social, en tanto mediación idónea, aunque parcial, de reconciliación en las sociedades complejas.
Desde Dialéctica de la Ilustración hasta Dialéctica negativa, el materialismo filosófico llevado adelante por T. W. Adorno ha ubicado en un lugar central de sus reflexiones la problemática de lo corporal, poniéndolo en discusión directa tanto con el psicoanálisis y su teoría de las pulsiones, así como con las diferentes versiones del idealismo. La reflexión acerca de este ámbito, permitirá exponer tanto el carácter represivo de la sociedad; también, la posibilidad de una ética verdaderamente democrática.
Este artículo rastrea las categorías del proyecto moral de Adorno a partir de la barbarie experimentada en los campos de concentración nazi durante la Segunda Guerra mundial. Para ello, el autor utiliza la estrategia de pensar la filosofía a partir del modelo de la Teoría Crítica de la Escuela de Frankfort. Este novedoso proyecto orienta al hombre o cualquier idea de filosofía y ética con sentido, atendiendo nuevas categorías de la realidad fáctica. Concretamente, Adorno construye un proyecto moral que tiene como fundamento, primero, un nuevo marco para la metafísica y antropología a partir de Auschwitz y, segundo, direccionado a evitar que nuevas expresiones de barbarie como esta se repitan. Adorno expone las categorías éticas en Meditaciones sobre la metafísica en su obra Dialéctica Negativa.
The paper discusses the policy implications of the Wirecard scandal. The study finds that all lines of defense against corporate fraud, including internal control systems, external audits, the oversight bodies for financial reporting and auditing and the market supervisor, contributed to the scandal and are in need of reform. To ensure market integrity and investor protection in the future, the authors make eight suggestions for the market and institutional oversight architecture in Germany and in Europe.
Banks are not immune from COVID-19. The economic downturn may drive some banks to the point of non-viability (PONV). If so, is the resolution regime in the Euro-area ready to respond? No, for banks may not have the right amount of the right kind of liabilities to make bail-in work. That could lead to a banking crisis. The Euro area can avoid this risk, by arranging now for a recap later. This would plug the gap between what the failing bank has and what it would need to make bail-in work. To do so, banks would pay – possibly via the contributions they make to the Single Resolution Fund – a commitment fee to a European backstop authority for a mandatory, system-wide note issuance facility. This would compel each bank, as it approached or reached the PONV, to issue to the backstop, and the backstop to purchase from the bank, the obligations the failing bank needs in order to make bail-in work. Such obligations would take the form of “senior-most” non-preferred debt, and bail-in would stop with such debt. That would allow the SRB to use the bail-in tool to resolve the failed bank, reopen it and run it under a solvent wind-down strategy. That protects counterparties and customers and ensures the continuity of critical economic functions. It also keeps investors at risk and promotes market discipline. Above all, it preserves financial stability.
The turnover time of terrestrial carbon (τ) controls the global carbon cycle – climate feedback and, yet, is poorly simulated by the current Earth System Models (ESMs). In this study, by assessing apparent carbon turnover time as the ratio between carbon stocks and fluxes, we provide a new, updated ensemble of diagnostic terrestrial carbon turnover times and associated uncertainties on a global scale using multiple, state-of-the-art, observation-based datasets of soil organic carbon stock (Csoil), vegetation biomass (Cveg) and gross primary productivity (GPP). Using this new ensemble, we estimated the global average τ to be 42$% &' years when the full soil depth is considered, longer than the previous estimates of 23$) &* years. Only considering the top 1 m (assuming maximum active layer depth is up to 1 meter) of soil carbon in circumpolar regions yields a global τ of 35$) &' years. Csoil in circumpolar regions account for two thirds of the total uncertainty in global τ estimates, whereas Csoil in non-circumpolar contributes merely 9.38%. GPP (2.25%) and Cveg (0.05%) contribute even less to the total uncertainty. Therefore, the high uncertainty in Csoil is the main factor behind the uncertainty in global τ, as reflected in the larger range of full-depth Csoil (3152-4372 PgC). The uncertainty is especially high in circumpolar regions with a behaviour of ESMs which could contribute to uncertainty reductions in future projections of the carbon cycle - climate feedback. The dataset of the terrestrial turnover time ensemble (DOI: 10.17871/bgitau.201911) is openly available from the data portal: https://doi.org/10.17871/bgitau.201911 (Fan et al., 2019) uncertainty of 50% and the spatial correlations among different datasets are also low compared to other regions. Overall, we argue that current global datasets do not support robust estimates of τ globally, for which we need clarification on variations of Csoil with soil depth and stronger estimates of Csoil in circumpolar regions. Despite the large variation in both magnitude and spatial patterns of τ, we identified robust features in the spatial patterns of τ that emerge regardless of soil depth and differences in data sources of Csoil, Cveg and GPP. Our findings show that the latitudinal gradients of τ are consistent across different datasets and soil depth. Furthermore, there is a strong consensus on the negative correlation between τ and temperature along latitude that is stronger in temperate zones (30ºN-60ºN) than in subtropical and tropical zones (30ºS30ºN). The identified robust patterns can be used to infer the response of τ to climate and for constraining contemporaneous behaviour of ESMs which could contribute to uncertainty reductions in future projections of the carbon cycle - climate feedback. The dataset of the terrestrial turnover time ensemble (DOI:10.17871/bgitau.201911) is openly available from the data portal: https://doi.org/10.17871/bgitau.201911 (Fan et al., 2019).
The turnover time of terrestrial ecosystem carbon is an emergent ecosystem property that quantifies the strength of land surface on the global carbon cycle–climate feedback. However, observation- and modeling-based estimates of carbon turnover and its response to climate are still characterized by large uncertainties. In this study, by assessing the apparent whole ecosystem carbon turnover times (τ) as the ratio between carbon stocks and fluxes, we provide an update of this ecosystem level diagnostic and its associated uncertainties in high spatial resolution (0.083∘) using multiple, state-of-the-art, observation-based datasets of soil organic carbon stock (Csoil), vegetation biomass (Cveg) and gross primary productivity (GPP). Using this new ensemble of data, we estimated the global median τ to be 43+7−7 yr (median+difference to percentile 75−difference to percentile 25) when the full soil is considered, in contrast to limiting it to 1 m depth. Only considering the top 1 m of soil carbon in circumpolar regions (assuming maximum active layer depth is up to 1 m) yields a global median τ of 37+3−6 yr, which is longer than the previous estimates of 23+7−4 yr (Carvalhais et al., 2014). We show that the difference is mostly attributed to changes in global Csoil estimates. Csoil accounts for approximately 84 % of the total uncertainty in global τ estimates; GPP also contributes significantly (15 %), whereas Cveg contributes only marginally (less than 1 %) to the total uncertainty. The high uncertainty in Csoil is reflected in the large range across state-of-the-art data products, in which full-depth Csoil spans between 3362 and 4792 PgC. The uncertainty is especially high in circumpolar regions with an uncertainty of 50 % and a low spatial correlation between the different datasets (0.2<r<0.5) when compared to other regions (0.6<r<0.8). These uncertainties cast a shadow on current global estimates of τ in circumpolar regions, for which further geographical representativeness and clarification on variations in Csoil with soil depth are needed. Different GPP estimates contribute significantly to the uncertainties of τ mainly in semiarid and arid regions, whereas Cveg causes the uncertainties of τ in the subtropics and tropics. In spite of the large uncertainties, our findings reveal that the latitudinal gradients of τ are consistent across different datasets and soil depths. The current results show a strong ensemble agreement on the negative correlation between τ and temperature along latitude that is stronger in temperate zones (30–60∘ N) than in the subtropical and tropical zones (30∘ S–30∘ N). Additionally, while the strength of the τ–precipitation correlation was dependent on the Csoil data source, the latitudinal gradients also agree among different ensemble members. Overall, and despite the large variation in τ, we identified robust features in the spatial patterns of τ that emerge beyond the differences stemming from the data-driven estimates of Csoil, Cveg and GPP. These robust patterns, and associated uncertainties, can be used to infer τ–climate relationships and for constraining contemporaneous behavior of Earth system models (ESMs), which could contribute to uncertainty reductions in future projections of the carbon cycle–climate feedback. The dataset of τ is openly available at https://doi.org/10.17871/bgitau.201911 (Fan et al., 2019).
We construct a new equation of state for the baryonic matter under an intense magnetic field within the framework of covariant density functional theory. The composition of matter includes hyperons as well as Δ-resonances. The extension of the nucleonic functional to the hypernuclear sector is constrained by the experimental data on Λ and Ξ-hypernuclei. We find that the equation of state stiffens with the inclusion of the magnetic field, which increases the maximum mass of neutron star compared to the non-magnetic case. In addition, the strangeness fraction in the matter is enhanced. Several observables, like the Dirac effective mass, particle abundances, etc. show typical oscillatory behavior as a function of the magnetic field and/or density which is traced back to the occupation pattern of Landau levels.
Glia, the helper cells of the brain, are essential in maintaining neural resilience across time and varying challenges: By reacting to changes in neuronal health glia carefully balance repair or disposal of injured neurons. Malfunction of these interactions is implicated in many neurodegenerative diseases. We present a reductionist model that mimics repair-or-dispose decisions to generate a hypothesis for the cause of disease onset. The model assumes four tissue states: healthy and challenged tissue, primed tissue at risk of acute damage propagation, and chronic neurodegeneration. We discuss analogies to progression stages observed in the most common neurodegenerative conditions and to experimental observations of cellular signaling pathways of glia-neuron crosstalk. The model suggests that the onset of neurodegeneration can result as a compromise between two conflicting goals: short-term resilience to stressors versus long-term prevention of tissue damage.
The miRNA biogenesis is tightly regulated to avoid dysfunction and consequent disease development. Here, we describe modulation of miRNA processing as a novel noncanonical function of the 5-lipoxygenase (5-LO) enzyme in monocytic cells. In differentiated Mono Mac 6 (MM6) cells, we found an in situ interaction of 5-LO with Dicer, a key enzyme in miRNA biogenesis. RNA sequencing of small noncoding RNAs revealed a functional impact, knockout of 5-LO altered the expression profile of several miRNAs. Effects of 5-LO could be observed at two levels. qPCR analyses thus indicated that (a) 5-LO promotes the transcription of the evolutionarily conserved miR-99b/let-7e/miR-125a cluster and (b) the 5-LO-Dicer interaction downregulates the processing of pre-let-7e, resulting in an increase in miR-125a and miR-99b levels by 5-LO without concomitant changes in let-7e levels in differentiated MM6 cells. Our observations suggest that 5-LO regulates the miRNA profile by modulating the Dicer-mediated processing of distinct pre-miRNAs. 5-LO inhibits the formation of let-7e which is a well-known inducer of cell differentiation, but promotes the generation of miR-99b and miR-125a known to induce cell proliferation and the maintenance of leukemic stem cell functions.
Inflation ist ein Konstrukt. Sie wird von unterschiedlichen Akteur*innen unterschiedlich wahrgenommen. Zum Teil passiert dies, weil Warenkörbe differieren, zum Teil weil Erwartungen unterschiedlich gebildet werden. Dieser Beitrag diskutiert die Heterogenität der Infl ation und ihrer Wahrnehmung und was dies für die Zielgröße der Zentralbankpolitik bedeutet.
Inflation ist ein Konstrukt. Sie wird von unterschiedlichen Akteuren unterschiedlich wahrgenommen. Zum Teil passiert dies, weil Warenkörbe differieren, zum Teil weil Erwartungen unterschiedlich gebildet werden. Dieser Beitrag diskutiert die Heterogenität der Inflation und ihrer Wahrnehmung und was dies für die Zielgröße der Zentralbankpolitik bedeutet.
The paper compares provision of public infrastructure via public-private partnerships (PPPs) with provision under government management. Due to soft budget constraints of government management, PPPs exert more effort and therefore have a cost advantage in building infrastructure. At the same time, hard budget constraints for PPPs introduce a bankruptcy risk and bankruptcy costs. Consequently, if bankruptcy costs are high, PPPs may be less efficient than public management, although this does not result from PPPs’ higher interest costs.
We develop a novel empirical approach to identify the effectiveness of policies against a pandemic. The essence of our approach is the insight that epidemic dynamics are best tracked over stages, rather than over time. We use a normalization procedure that makes the pre-policy paths of the epidemic identical across regions. The procedure uncovers regional variation in the stage of the epidemic at the time of policy implementation. This variation delivers clean identification of the policy effect based on the epidemic path of a leading region that serves as a counterfactual for other regions. We apply our method to evaluate the effectiveness of the nationwide stay-home policy enacted in Spain against the Covid-19 pandemic. We find that the policy saved 15.9% of lives relative to the number of deaths that would have occurred had it not been for the policy intervention. Its effectiveness evolves with the epidemic and is larger when implemented at earlier stages.
This essay argues for the philosophical standing of Walter Benjamin’s early work and posits a deeper continuity between this early work as a philosopher and the subsequent development of his work as a writer. When these fragments are read in proper relation to each other, they reveal for the first time many of the key innovations of Benjamin as a philosopher, as well as his points of influence on Horkheimer and Adorno. His early ‘Program’ critiques the Enlightenment conception of experience as a means for gaining empirical knowledge, and announces the need for a new concept of experience. Benjamin follows through on this program with a method of philosophical enquiry that is by turns fragmentary and constellational, developing a series of provisional notions of experience, which form a constellation with one another: perception, mimesis, language as a medium of experience, observation and memory.
This article is an inquiry into the concept of metaphysical experience through a joint discussion of two authors and philosophers with different approaches that nevertheless converge in the reclamation of the concept and rely both on the experience of death as an example. In both cases, the authors are guided by the central problem of how not to relinquish metaphysical experience to unscrutinized immediacy or a powerful conversion which enjoins subjection, putting it in contact with aesthetics and ethics at once. Theodor Adorno situates metaphysical experience as a problem of philosophy of history and devotes attention to the contemporary possibility of experiences that evoke transcendence. The transformations he identifies in the concept also lead him to propose art as a domain where metaphysical experience is alive. The implicit personal investment Adorno makes is much more clear in Lacoue-Labarthe who, in a dialogue with Maurice Blanchot, shows the experience as deeply bound up with literature and its links to subjectivity. The article argues that the main difference between the two approaches is modal and temporal from the side of the object, aside from the different modes of interrogation recognized with the labels deconstruction and critical theory.
La sfida del nominalismo alla realtà degli universali (sia in filosofia che in teologia) è stata un motore del pensiero moderno. Tradotta in termini estetici, ha favorito la resistenza alle generiche convenzioni e ha contribuito a minare le nozioni essenzialiste della forma estetica. Theodor W. Adorno ebbe una risposta tipicamente dialettica al nominalismo, plaudendo alla sua sovversione delle reificazioni categoriche, ma allarmato dal suo livellamento indiscriminato della distinzione tra concetto e oggetto, che poteva anche cancellare la distinzione tra opere d'arte e oggetti di uso quotidiano. In termini musicali, ha apprezzato l'enfasi nominalista sui singoli lavori rispetto alle generiche categorie formali e ha elogiato la rivoluzione atonale di Arnold Schoenberg. Ma era anche consapevole del fatto che, portato all'estremo, il nominalismo poteva condurre al dominio soggettivo di una natura considerata priva di proprie caratteristiche essenziali. Nella sua tardiva riflessione sulla musique informelle, ammirò una musica che evitava sia le categorie reificate che il dominio soggettivo dell'apparente contingenza del mondo materiale, una musica che esprimeva un nominalismo che avrebbe potuto essere meglio chiamato "magico" piuttosto che "convenzionale".
Two main types of methods are used in gene therapy: integrating vectors and nuclease-based genome engineering. Nucleases are site-specific and are efficient for knock-outs, but inefficient at inserting long DNA sequences. Integrating vectors perform this task with high efficiency, but their insertion occurs at random genomic positions. This can result in transformation of target cells, which leads to severe adverse events in a gene therapy context. Thus, it is of great interest to develop novel genome engineering tools that combine the advantages of both technologies. The main focus of this thesis is on generating such a targetable integrating vector.
The integrating vector used in this project is the Sleeping Beauty (SB) transposon, a DNA transposon characterized by high activity across a wide range of cells. The SB transposase was combined with an RNA-guided Cas9 nuclease domain. This nuclease component was meant to direct transposase integration to specific targets defined by RNAs. The SB transposase was fused to cleavage-inactivated Cas9 (dCas9) to tether it to the target sites. In addition, adapter proteins consisting of dCas9 and domains non-covalently interacting with SB transposase or the SB transposon were generated. All constituent domains of these fusion proteins were tested in enzymatic assays and almost all enzymatic activities could be verified.
Combining the fusion protein dCas9-SB100X with a gRNA binding a sequence from the AluY repetitive element resulted in a weak, but statistically significant enrichment around sites bound by the gRNA. This enrichment was ca. 2-fold and occurred within a 300 bp window downstream of target sites, or within the AluY element.
Targeting with adapter proteins and targeting of other targets (L1 elements or single-copy targets) did not result in statistically significant effects. Single-copy targets tested included the HPRT gene and three specifically selected GSH targets that were known to be receptive to SB insertions. The combination with a more sequence-specific transposase mutant also failed to increase specificity to a level allowing targeting of single-copy loci. Genome-wide analysis of insertions however demonstrated, that dCas9-SB100X has a different insertion profile than SB100X, regardless of the gRNA used.
As low efficiency of retargeting is likely a consequence of the high background activity of the SB100X transposase in the fusion constructs, a SB mutant with reduced DNA affinity, SB(C42), was generated. For this mutant, transposition activity was partly dependent on a dCas9 domain being supplied with a multi-copy target gRNA, specifically a 2-fold increase in the presence of a AluY-directed gRNA. Whether using this mutant results in improved targeting remains to be determined.
In a side project, an attempt was made to direct SB insertions to ribosomal DNA by fusing the transposase to a nucleolar protein. This fusion transposase partially localized to nucleoli and insertions catalyzed by this transposase were found to be enriched in nucleolus organizer regions (NORs) and nucleolus-associated domains (NADs).
The aim of a second side project was increasing the ratio between homology-directed repair (HDR) and non-homologous end-joining (NHEJ) at Cas9-mediated double-strand breaks (DSBs). To achieve this, Cas9 was fused to DNA-interacting domains and corresponding binding sequences were fused to the homology donors. While an increased HDR/NHEJ ration could be observed for the fusion proteins, it was not dependent on the presence on the binding sequences in the donor molecules.
This essay focuses on the relationship between solipsism and aesthetic subjectivity, as outlined in Adorno’s Aesthetic Theory. As he mentions, according to dialectical materialism, solipsism gained actuality within (radical) modernism as general “standpoint”, realized in atomistic society through “reified division of labor”. This also applies to artistic production. At the same time, solipsism constitutes a long standing philosophical hypothesis, which concerns the truth value of perception, thus imitating the “subjective point of reference in art”. Therefore, Adorno’s brief statements on the relationship between epistemological solipsism and immanent artistic subjectivity designate different phenomena under the same heading; these concern sociological, cognitive and existential aspects of artistic creation and aesthetic experience, sedimented in the artwork’s content. However, he often undertakes abrupt conceptual transitions within them. In this essay, I mainly focus on the cognitive aspect, especially on the relationship between solipsism and art’s “subjective point of reference”. For this purpose, I reconstruct Adorno’s relevant ideas on the role of subjectivity within art and relate them to his elaborated analysis of the process of aesthetic experience. Finally, I scrutinize the value of this non-apodictic truth and its relationship to particular aspects of “truth-content” and to Adorno’s redemption of the artwork’s fragile ontological status, its semblance character.
Negatività, trascendenza, utopia. La dialettica dell'opera d'arte nella Teoria estetica di Adorno
(2018)
Il seguente saggio, tenta di mettere a fuoco la relazione tra negatività e trascendenza così come emerge all'interno della riflessione estetica di Theodor Wiesengrund Adorno. La trascendenza, la relazione con l'eterogeneneo e l'alterità, e la dimensione riflessiva che, secondo Adorno, caratterizzano l'opera d'arte moderna, riguardano, in primo luogo, la ineliminabile tensione dell'opera d'arte verso il senso e, nello stesso tempo, l'impossibilità che esso possa totalmente compiersi all'interno dell'esperienza. In questa prospettiva, in un mondo dominato dal rischio della totale coincidenza tra opera e merce, fino alla identificazione tra arte e industria culturale, per Adorno, l'opera d'arte non si costituisce come tale per ciò che attraverso di essa si realizza, quanto, e forse soprattutto, per ciò che in essa rimane allo stato della potenza, per le possibilità intraviste che si conservano al suo interno che, coincidendo con la sua dimensione utopica, impediscono la piena identificazione tra opera d'arte e merce di consumo. Ciò che conta, da questo punto di vista, non è solo il passaggio da un senso potenziale a un significato determinato, né quello dal possibile al reale, quanto piuttosto - attraverso la continua e dialettica relazione tra essenza e apparenza, linguaggio e realtà, pensiero e sensibilità -, la contingenza stessa del significare e, di qui, la sua possibilità di non-essere o di essere-altrimenti.
A Large Ion Collider Experiment (ALICE) is one of the four large experiments at the Large Hadron Collider (LHC) at the European Organization for Particle Physics (CERN). ALICE focuses on the physics of the strong interaction and in particular on the Quark-Gluon Plasma. This is a state of matter in which quarks are de-confined. It is believed that it existed in the earliest moments of the evolution of the universe. The ALICE detector studies the products of the collisions between heavy-nuclei, between protons, and between protons and heavy-nuclei. The sub-detector closest to the interaction point is the Inner Tracking System (ITS), which is used to measure the momentum and trajectory of the particles generated by the collisions and allows reconstructing primary and secondary interaction vertices. The ITS needs to have an accurate spatial resolution, together with a low material budget to limit the effect of multiple scattering on low-energetic particles to precisely reconstruct their trajectory. During the Long Shutdown 2 (2019-2020) of the LHC, the current ITS will be replaced by a completely redesigned sub-detector, which will improve readout rate and particle tracking performance especially at low-momentum.
The ALice PIxel DEtector (ALPIDE) chip was designed to meet the requirements of the upgraded ITS in terms of resolution, material budget, radiation hardness, and readout rate. The ALPIDE chip is a Monolithic Active Pixel Sensor (MAPS) realised in Complementary Metal-Oxide Semiconductor (CMOS) technology. Sensing element, analogue front-end, and its digital readout are integrated into the same silicon die. The readout architecture of the new ITS foresees that data is transmitted via a high-speed serial link directly from the ALPIDE to the off-detector electronics. The data is transmitted off-chip by a so-called Data Transmission Unit (DTU) which needs to be tolerant to Single-Event Effects induced by radiation, in order to guarantee reliable operation. The ALPIDE chip will operate in a radiation field with a High-Energy Hadron peak flux of 7.7·10^5 cm^-2s^-1.
The data are sent by the ALPIDE on copper cables to the readout system, which aggregates them and re-transmits them via optical fibres to the counting room. The position where the readout electronics will be placed is constrained by the maximum transmission distance reasonably achievable by the ALPIDE Data Transmission Unit and mechanical constraints of the ALICE experiment. The radiation field at that location is not negligible for its effects on electronics: the high-energy hadrons flux can reach 10^3 cm^-2s^-1. Static RAM (SRAM)-based Field Programmable Gate Arrays (FPGAs) are favoured over Application Specific Integrated Circuits (ASICs) or Radiation Hard by Design (RHBD) commercial devices because of cost effectiveness. Moreover, SRAM-based FPGAs are re-configurable and provide the data throughput required by the ITS. The main issue with SRAM-based FPGAs, for the intended application, is the susceptibility of their Configuration RAM (CRAM) to Single-Event Upsets: the number of CRAM bits is indeed much higher than the logic they configure. Total Ionizing Dose (TID) at the readout designed position is indeed still acceptable for Component Off The Shelf (COTS), provided that proper verification is carried out.
This dissertation focuses on two parts of the design of the readout system: the Data Transmission Unit of the ALPIDE chip and the design of fundamental modules for the SRAM-based FPGA of the readout electronics. In the first part, a module of the Data Transmission Unit is designed, optimising the trade-off between power consumption, radiation tolerance, and jitter performance. The design was tested and thoroughly characterised, including tests while under irradiation with a 30 MeV protons. Furthermore the Data Transmission Unit performance was validated after the integration into the first prototypes of ITS modules. In the second part, the problem of developing a radiation-tolerant SRAM-based FPGA design is investigated and a solution is provided. First, a general methodology for designing radiation-tolerant Finite State Machines in SRAM-based FPGAs is analysed, implemented, and verified. Later, the radiation-tolerant FPGA design for the ITS readout is described together with the radiation effects mitigation techniques that were selectively applied to the different modules. The design was tested with multiple irradiation tests and the results are stated below.
Proteine sind die Maschinen der Zellen. Um die Funktionalität von zahlreichen zellulären Prozessen zu gewährleisten, müssen Kommunikationssignale innerhalb von Proteinen weitergeleitet werden. Die Weiterleitung einer Störung an einem Ort im Protein zu einer entfernten Stelle, an welcher sie strukturelle und/oder dynamische Änderungen auslöst, wird Allosterie genannt. Zunächst wurde Allosterie hauptsächlich mit großräumigen Konformationsänderungen in Verbindung gebracht, aber später entwickelte sich ein dynamischerer Blickwinkel auf Allosterie in Abwesenheit dieser großräumigen Konformationsänderungen. Die Idee eines allosterischen Pfades bestehend aus konservierten und energetisch gekoppelten Aminosäuren, welche die Signalweiterleitung zwischen entfernten Stellen im Protein vermitteln, entstand. Diese allosterischen Pfade wurden durch zahlreiche theoretische Studien in Zusammenhang mit Pfaden effizienten anisotropen Energieflusses gebracht. Der Energiefluss entlang dieser Netzwerke verknüpft allosterische Signalübertragung mit Schwingungsenergietransfer (VET - vibrational energy transfer). Die Großzahl der Forschungsarbeiten über dynamische Allosterie basiert auf theoretischen Methoden, weil nur wenige geeignete experimentelle Verfahren existieren. Um diesen essentiellen biologischen Prozess der Informationsübertragung besser verstehen zu können, ist die Entwicklung neuer und leistungsstarker experimenteller Instrumente und Techniken daher dringend erforderlich. Die vorliegende Dissertation setzt sich dies zum Ziel.
VET in Proteinen ist aufgrund der Proteingeometrie inhärent anisotrop. Alle globulären Proteine besitzen Kanäle effizienten Energieflusses, von denen vermutet wird, dass sie wichtig für Proteinfunktionen, wie die schnelle Ableitung von überschüssiger Wärme, Ligandenbindung und allosterische Signalweiterleitung, sind. VET kann mit zeitaufgelöster Infrarot (IR) Spektroskopie untersucht werden, bei welcher ein Femtosekunden Anregepuls eines Lasers Schwingungsenergie in ein molekulares System an einer bestimmten Stelle injiziert und ein, nach einem veränderbarem Zeitintervall folgender, IR Abfragepuls die Ausbreitung dieser Schwingungsenergie detektiert. Ein protein-kompatibler und universell einsetzbarer Chromophor, der die Energie eines sichtbaren Photons in Schwingungsenergie konvertiert, wird als Heizelement benötigt um langreichweitige VET Pfade in Proteinen kartieren zu können. Der Azulen (Azu) Chromophor eignet sich dafür, weil er nach Photoanregung des ersten elektronischen Zustandes durch ultraschnelle interne Konversion fast die gesamte injizierte Energie innerhalb von einer Picosekunde in Schwingungsenergie umwandelt. Eingebettet in die nicht-kanonische Aminosäure (ncAA - non-canonical amino acid) ß-(1-Azulenyl)-L-Alanine (AzAla), kann der Azu Rest in Proteine eingebaut werden. Die Ankunft der injizierten Schwingungsenergie an einer bestimmten Stelle im Protein kann mithilfe eines IR Sensors detektiert werden. Die Kombination aus Azu als VET Heizelement und Azidohomoalanine (Aha) als VET Sensor mit transienter IR (TRIR) Spektroskopie wurde schon erfolgreich an kleinen Peptiden in der Dissertation von H. M. Müller-Werkmeister getestet, die der vorliegenden Dissertation in den Laboren der Bredenbeck Gruppe vorausging.
Die Schwingungsfrequenz chemischer Bindungen ist hochempfindlich auf selbst kleine Änderungen der Konformation und Dynamik in der unmittelbaren Umgebung und kann mit IR Spektroskopie gemessen werden, z. B. mit Fourier Transform IR (FTIR) Spektroskopie. IR Spektroskopie bietet eine außergewöhnlich gute Zeitauflösung, die es ermöglicht, dynamische Prozesse in Molekülen auf einer Zeitskala von wenigen Picosekunden zu beobachten, wie z. B. die ultraschnelle Weiterleitung von Schwingungsenergie. Mit zweidimensionaler (2D)-IR Spektroskopie können die Relaxation von schwingungsangeregten Zuständen und strukturelle Fluktuationen um die schwingende Bindung untersucht werden. Allerdings geht die herausragende Zeitauflösung mit limitierter spektraler Auflösung einher. In größeren Molekülen mit zahlreichen Bindungen überlagern sich die Schwingungsbanden und die Ortsauflösung geht verloren. Um diese Limitierung zu überwinden, können IR Marker benutzt werden, chemische Gruppen, die in einer spektral durchsichtigen Region des Protein/Wasser Spektrums (1800 bis 2500 cm-1) absorbieren. Als ncAA können sie kotranslational in Proteine an einer gewünschten Stelle eingebaut werden und so ortsspezifische Informationen aus dem Proteininneren liefern. Aufgrund ihrer geringen Größe, eines relativ großen Extinktionskoeffizientens (350-400 M-1cm-1) und einer hohen Empfindlichkeit auf Änderungen in der lokalen Umgebung sind organische Azide (N3) wie zum Beispiel Aha besonders geeignete IR Marker. Aha kann als Methionin Analogon ins Protein eingebaut werden.
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The role of radiation therapy in the treatment of (colo)-rectal cancer has changed dramatically over the past decades. Introduced with the aim of reducing the high rates of local recurrences after conventional surgery, major developments in imaging, surgical technique, systemic therapy and radiation delivery have now created a much more complex environment leading to a more personalized approach. Functional aspects including reduction of acute or late treatment-related side effects, sphincter or even organ-preservation and the unsolved problem of still high distant failure rates have become more important while local recurrence rates can be kept low in the vast majority of patients. This review summarizes the actual role of radiation therapy in different subgroups of patients with rectal cancer, including the current standard approach in different subgroups as well as recent developments focusing on neoadjuvant treatment intensification and/or non-operative treatment approaches aiming at organ-preservation.
The novel coronavirus infection (COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as adult respiratory syndrome, sepsis, coagulopathy, and death in a proportion of patients. Among other factors and direct viral effects, the increase in the vasoconstrictor angiotensin II, the decrease in the vasodilator angiotensin, and the sepsis-induced release of cytokines can trigger a coagulopathy in COVID-19. A coagulopathy has been reported in up to 50% of patients with severe COVID-19 manifestations. An increase in d-dimer is the most significant change in coagulation parameters in severe COVID-19 patients, and progressively increasing values can be used as a prognostic parameter indicating a worse outcome. Limited data suggest a high incidence of deep vein thrombosis and pulmonary embolism in up to 40% of patients, despite the use of a standard dose of low-molecular-weight heparin (LMWH) in most cases. In addition, pulmonary microvascular thrombosis has been reported and may play a role in progressive lung failure. Prophylactic LMWH has been recommended by the International Society on Thrombosis and Haemostasis (ISTH) and the American Society of Hematology (ASH), but the best effective dosage is uncertain. Adapted to the individual risk of thrombosis and the d-dimer value, higher doses can be considered, especially since bleeding events in COVID-19 are rare. Besides the anticoagulant effect of LMWH, nonanticoagulant properties such as the reduction in interleukin 6 release have been shown to improve the complex picture of coagulopathy in patients with COVID-19.
Neutron total cross sections are an important source of experimental data in the evaluation of neutron-induced cross sections. The sum of all neutron-induced reaction cross sections can be determined with a precision of a few per cent in a relative measurement. The neutron spectrum of the photoneutron source nELBE extends in the fast region from about 100 keV to 10 MeV and has favourable conditions for transmission measurements due to the low instantaneous flux of neutrons and low gamma-flash background. Several materials of interest (in part included in the CIELO evaluation or on the HPRL of OECD/NEA) have been investigated: 197Au [1, 2], natFe [2], natW [2], 238U, natPt, 4He, natO, natNe, natXe. For gaseous targets high pressure gas cells with flat end-caps have been built that hold up to 200 bar pressure. The experimental setup will be presented including results from several transmission experiments and the data analysis leading to the total cross sections will be discussed.
Activations with neutrons in the keV energy range were routinely performed at the Karlsruhe Institute of Technology (KIT) in Germany in order to simulate stellar conditions for neutron-capture cross sections. A quasi-Maxwell-Boltzmann neutron spectrum of kT = 25 keV, being of interest for the astrophysical s-process, was produced by the 7Li(p,n) reaction utilizing a 1912 keV proton beam at the Karlsruhe Van de Graaff accelerator. Activated samples resulting in long-lived nuclear reaction products with half-lives in the order of yr 100 Myr were analyzed by Accelerator Mass Spectrometry (AMS). Comparison of the obtained reaction cross sections to literature data from previous Time-of-Flight (ToF) measurements showed that the selected AMS data are systematically lower than the ToF data. To investigate this discrepancy, 54Fe(n,γ)55Fe and 35Cl(n,γ)36Cl reaction cross sections were newly measured at the Frankfurt Neutron Source (FRANZ) in Germany. To complement the existing data, an additional neutron activation of 54Fe and 35Cl at a proton energy of 2 MeV was performed. The results will give implications for the stellar environment at kT = 90 keV, reaching the not yet experimentally explored high-energy s-process range. AMS measurements of the activated samples are scheduled.
Signaling pathways, depending on the second messenger molecule cAMP, modulate hippocampal cell signaling via influencing transcription factors like cAMP-regulated element-binding protein (CREB) or early growth response 1 EGR1/Krox24/zif268/ZENK (EGR1). Here, we investigated two reporter cell lines derived from an immortalized hippocampal neuronal cell line stably expressing a CRE- or EGR1-luciferase reporter gene (HT22CREluc and HT22EGR1luc, respectively). The cells were subjected to phosphodiesterase inhibitors and other cAMP-modulating agents to investigate dose- and time-dependent phosphodiesterase (PDE)-mediated fine-tuning of cAMP-dependent transcriptional signaling. The non-isoform-specific cyclic nucleotide phosphodiesterase (PDE) inhibitor isobutyl-methyl-xanthine (IBMX), as well as selective inhibitors of PDE3 (milrinone) and PDE4 (rolipram), were tested for their ability to elevate CRE- and EGR1-luciferase activity. Pharmacological parameters like onset of activity, maximum activity, and offset of activity were determined. In summary, phosphodiesterase inhibition appeared similarly potent in comparison to adenylate cyclase stimulation or direct activation of protein kinase A (PKA) via specific cAMP agonists and was at least partly mediated by PKA as shown by the selective PKA inhibitor <i>Rp</i>-8-Br-cAMPS. Moreover, transcriptional activation by PDE inhibition was also influenced by organic anion-exchanger action and interacted with fibroblast growth factor (FGF) receptor-mediated pathways.
Monitoring is an indispensable tool for the operation of any large installation of grid or cluster computing, be it high energy physics or elsewhere. Usually, monitoring is configured to collect a small amount of data, just enough to enable detection of abnormal conditions. Once detected, the abnormal condition is handled by gathering all information from the affected components. This data is processed by querying it in a manner similar to a database.
This contribution shows how the metaphor of a debugger (for software applications) can be transferred to a compute cluster. The concepts of variables, assertions and breakpoints that are used in debugging can be applied to monitoring by defining variables as the quantities recorded by monitoring and breakpoints as invariants formulated via these variables. It is found that embedding fragments of a data extracting and reporting tool such as the UNIX tool awk facilitates concise notations for commonly used variables since tools like awk are designed to process large event streams (in textual representations) with bounded memory. A functional notation similar to both the pipe notation used in the UNIX shell and the point-free style used in functional programming simplify the combination of variables that commonly occur when formulating breakpoints.
A concepção de indivíduo na sociedade administrada é analisada por Horkheimer e Adorno (1973), no ensaio Indivíduo no livro Temas Básicos da Sociologia, cujo método de exposição instiga à reflexão sobre a concepção de indivíduo e as possibilidades de formação e educação na sociedade administrada, demonstrando que a concepção de indivíduo na Filosofia ora tendia para uma ênfase na subjetividade em detrimento das condições objetivas sociais, ora tendia à totalidade social, negligenciando a singularidade do indivíduo. Em seguida, estabelecem articulações entre as diferentes esferas complementares (indivíduo e sociedade) e as consequências sobre a formação do indivíduo e a educação na contemporaneidade, problematizadas por Adorno (2000), em sua obra Educação e Emancipação, quanto às suas possibilidades e limites na sociedade administrada.
Neste artigo trataremos de entender quais foram as principais propostas de Theodor W. Adorno, filósofo alemão e membro da Escola de Frankfurt, para a educação de seu tempo. A partir de uma análise, mesmo que marginal, de parte do conjunto substancial de seus escritos, palestras, entrevistas e debates, sobretudo da obra em conjunto com Horkheimer, “Dialética do Esclarecimento” e dos ensaios de “Educação e Emancipação”, este texto evidencia os pressupostos do pensamento adorniano, pautado na teoria crítica da sociedade, e elucida suas reflexões na tentativa de propor que a educação fosse mais política e baseada no esclarecimento e na emancipação. Modicamente, buscamos pensar a atualidade e a urgência de suas reflexões para o campo educacional contemporâneo.
O presente artigo visa a fazer algumas anotações sobre educação, emancipação e crítica social no pensamento de Theodor W. Adorno. Esses temas se relacionam direta e indiretamente nos escritos de Adorno e assinalam a coerência epistemológica da sua teoria crítica em relação a ambos. Desse modo, a questão que colocamos é a seguinte: como compreender a tensão presente entre as necessidades de uma educação para a emancipação e as condições para efetivá-la? Essa questão nos encaminha para outra: é possível relacionar, nos textos adornianos, uma perspectiva de se pensar a educação para a emancipação, articulada a uma crítica social no contexto atual? Primeiramente, fazemos uma breve incursão no que consiste o pensamento contra a barbárie em Adorno, sobretudo, a partir do sentido de Auschwitz como símbolo da relação entre civilização e barbárie que o autor faz. Num segundo momento, nos confrontamos com a questão da formação cultural na Teoria da Semiformação, cujo escopo do texto é apontar os limites da formação cultural e consequentemente os limites da educação no âmbito do capitalismo avançado. Por fim, pretendemos discutir a ideia de "crítica social" em Adorno, articulada aos temas anteriores, isto é, apontar algumas ponderações para uma educação contra a barbárie e a semiformação frentes aos desafios impostos pela sociedade atual.
The necessity of over-interpretation: Adorno, the essay, and the gesture of aesthetic experience
(2013)
This article is a discussion of Theodor W. Adorno’s comment, in the beginning of ‘The Essay as Form’, that interpretations of essays are over-interpretations. I argue that this statement is programmatic, and should be understood in the light of Adorno’s essayistic ideal of configuration, his notion of truth, and his idea of the enigmatic character of art. In order to reveal how this over-interpreting appears in practice, I turn to Adorno’s essay on Kafka. According to Adorno, the reader of Kafka is caught in an aporia: Kafka’s work cannot be interpreted, yet every single sentence calls for interpretation. This paradox is related to the gestures and images in Kafka’s work: like Walter Benjamin, Adorno means that they contain sedimented, forgotten experiences. Instead of interpreting these images, Adorno visualizes the experiences indirectly by presenting images of his own. His own essay becomes gestural.
‘Being with oneself in the other’ is a well-known formula that Hegel uses to characterize the basic relation of subjective freedom. This phrase points to the fact that subjects can only come to themselves if they remain capable of going beyond themselves. This motif also plays a significant role in Hegel’s philosophy of art. The article further develops this motif by exploring the extent to which this polarity of selfhood and otherhood is also characteristic of states of aesthetic freedom. It does not offer an exegesis of Hegel’s writings, but attempts to remain as close as possible to the spirit of Hegel’s philosophy – with some help from Kant and Adorno. The argument begins with some key terms on the general state of subjective freedom in order to distinguish it from the particular role of aesthetic freedom and then, finally, drawing again on Hegel, works out the sense in which aesthetic freedom represents an important variant of freedom.
Theodor W. Adorno’s criticism of human beings’ domination of nature is a familiar topic to Adorno scholars. Its connection to the central relationship between art and nature in his aesthetics has, however, been less analysed. In the following paper, I claim that Adorno’s discussion of art’s truth content (Wahrheitsgehalt) is to be understood as art’s ability to give voice to nature (both human and non-human) since it has been subjugated by the growth of civilization. I focus on repressed non-human nature and examine Adorno’s interpretation of Eduard Mörike’s poem ‘Mausfallen-Sprüchlein’ (Mousetrap rhyme). By giving voice to the repressed animal, Mörike’s poem manages to point towards the possibility of a changed relationship between mice and men, between nature and humanity, which is necessary in order to achieve reconciliation amongst humans as well.
Comprehensive analysis of tumour sub-volumes for radiomic risk modelling in locally advanced HNSCC
(2020)
Simple Summary: Radiomic risk models are usually based on imaging features, which are extracted from the entire gross tumour volume (GTV entire ). This approach does not explicitly consider the complex biological structure of the tumours. Therefore, in this retrospective study, we investigated the prognostic value of radiomic analyses based on different tumour sub-volumes using computed tomography imaging of patients with locally advanced head and neck squamous cell carcinoma who were treated with primary radio-chemotherapy. The GTV entire was cropped by different margins to define the rim and corresponding core sub-volumes of the tumour. Furthermore, the best performing tumour rim sub-volume was extended into surrounding tissue with different margins. As a result, the models based on the 5 mm tumour rim and on the 3 mm extended rim sub-volume showed an improved performance compared to models based on the corresponding tumour core. This indicates that the consideration of tumour sub-volumes may help to improve radiomic risk models.
Abstract: Imaging features for radiomic analyses are commonly calculated from the entire gross tumour volume (GTVentire). However, tumours are biologically complex and the consideration of different tumour regions in radiomic models may lead to an improved outcome prediction. Therefore, we investigated the prognostic value of radiomic analyses based on different tumour sub-volumes using computed tomography imaging of patients with locally advanced head and neck squamous cell carcinoma. The GTVentire was cropped by different margins to define the rim and the corresponding core sub-volumes of the tumour. Subsequently, the best performing tumour rim sub-volume was extended into surrounding tissue with different margins. Radiomic risk models were developed and validated using a retrospective cohort consisting of 291 patients in one of the six Partner Sites of the German Cancer Consortium Radiation Oncology Group treated between 2005 and 2013. The validation concordance index (C-index) averaged over all applied learning algorithms and feature selection methods using the GTVentire achieved a moderate prognostic performance for loco-regional tumour control (C-index: 0.61 ± 0.04 (mean ± std)). The models based on the 5 mm tumour rim and on the 3 mm extended rim sub-volume showed higher median performances (C-index: 0.65 ± 0.02 and 0.64 ± 0.05, respectively), while models based on the corresponding tumour core volumes performed less (C-index: 0.59 ± 0.01). The difference in C-index between the 5 mm tumour rim and the corresponding core volume showed a statistical trend (p = 0.10). After additional prospective validation, the consideration of tumour sub-volumes may be a promising way to improve prognostic radiomic risk models.
Frente al positivismo racionalista, que sólo cree en el poder de la razón filosófica y que considera que el mundo es esencialmente racional y justo, y frente al tragicismo, que sostiene que la realidad carece de sentido y orden, y que por tanto sólo la poesía puede comprenderla, la actitud postrágica de Ortega, Heidegger y Adorno, afirma que sólo en la tensión entre filosofía y poesía puede salvarse el ser humano, porque sólo esa colaboración y diálogo le permite acceder al ser.
Quando se acompanha o discurso filosófico acerca da sensibilidade artística, salta aos olhos que nele impera uma dupla tendência no que se refere aos recursos expressivos. Por um lado, nota-se que os meios de expressão acabam resistindo uns em relação aos outros; por outro, percebe-se que tal resistência também se revela bastante fraca, descerrando novas fronteiras e ocasionando ulteriores transições. Tendo isso em vista, o propósito geral do presente artigo consiste em pôr à prova a hipótese de que é no âmbito da música que a moderna ponderação estética descobre o sentido e o alcance do vínculo entre as artes, forjado, em geral, nos termos da auto-compreensão das vanguardas artísticas. Trata-se, em suma, de refazer os passos por meio dos quais a música terminou por se converter, no século XIX, num dos mais importantes veículos de ideias para, a partir do ponto de inflexão representado pela filosofia nietzschiana da maturidade, trazer à plena luz a concepção de "emaranhamento" [Verfransung] das artes, a qual ganha relevo, em especial, na derradeira etapa do itinerário intelectual de Th. W. Adorno.
O objetivo do texto é propor uma interpretação do conceito de sublime na Teoria estética de Theodor Adorno, partindo do confronto com leituras significativas de outros comentadores, de modo a fornecer uma concepção que associe o movimento de transcendência e alteridade da forma estética à dinâmica histórico-processual das obras.
O objetivo do texto é fazer uma análise da dimensão crítica do conceito de indústria cultural proposto por Adorno e Horkheimer a partir da noção psicanalítica de narcisismo, tal como Adorno a interpretou. A cultura de massa será vista como propiciando o prazer substancialmente ilusório de satisfazer a ânsia de engrandecimento do ego, no mesmo instante em que mantém o indivíduo atado às tendências inerciais de unificação social.
Em defesa de Adorno: a propósito das críticas endereçadas por Giorgio Agamben à dialética adorniana
(2007)
Pensador dos mais instigantes da atualidade, Giorgio Agamben explora, em boa parte de seus ensaios filosóficos, a significação excepcional que apresenta Auschwitz para a compreensão de nossa modernidade esclarecida, significação esta que Adorno foi um dos primeiros a acusar. Sob o pano de fundo dessa convergência temática existente entre os dois pensadores, empreende-se aqui uma apreciação das críticas que Agamben endereça à filosofia de Adorno. Seria justo recriminar a dialética negativa adorniana por não ter sido capaz de se libertar do pendor idealista da dialética hegeliana? Seria justo censurá-la por ter sucumbido a uma espécie de estetização do messianismo, como sentencia Agamben? Essas questões são respondidas em defesa de Adorno.
CGC aktuell 01/2020
(2020)
Simple Summary: Therapeutic antibodies are an integral part of treatment regimens for metastasized colorectal cancer. In KRAS wildtype tumors both bevacizumab and cetuximab are active. While bevacizumab has previously been shown to induce tumor hypoxia, we here report that EGFR inhibition by cetuximab protects colon cancer cells from hypoxia-induced cell death. This effect appears to be responsible for the inferior efficacy of a treatment sequence of bevacizumab followed by cetuximab versus an inverse sequence that we observed in a colorectal cancer mouse model. It also offers a mechanistic explanation for effects observed in clinical trials such as underadditive or even detrimental effects when combining bevacizumab and cetuximab (CAIRO2 trial) and the superior efficacy of first line cetuximab (FIRE-3 trial) under chemotherapy backbones in colorectal cancer.
Abstract: Monoclonal antibodies like cetuximab, targeting the epidermal growth factor receptor (EGFR), and bevacizumab, targeting the vascular endothelial growth factor (VEGF), are an integral part of treatment regimens for metastasized colorectal cancer. However, inhibition of the EGFR has been shown to protect human glioma cells from cell death under hypoxic conditions. In colon carcinoma cells, the consequences of EGFR blockade in hypoxia (e.g., induced by bevacizumab) have not been evaluated yet. LIM1215 and SW948 colon carcinoma and LNT-229 glioblastoma cells were treated with cetuximab, PD153035, and erlotinib and analyzed for cell density and viability. The sequential administration of either cetuximab followed by bevacizumab (CET->BEV) or bevacizumab followed by cetuximab (BEV->CET) was investigated in a LIM1215 (KRAS wildtype) and SW948 (KRAS mutant) xenograft mouse model. In vitro, cetuximab protected from hypoxia. In the LIM1215 model, a survival benefit with cetuximab and bevacizumab monotherapy was observed, but only the sequence CET->BEV showed an additional benefit. This effect was confirmed in the SW948 model. Our observations support the hypothesis that bevacizumab modulates the tumor microenvironment (e.g., by inducing hypoxia) where cetuximab could trigger protective effects when administered later on. The sequence CET->BEV therefore seems to be superior as possible mutual adverse effects are bypassed.
Background: Hyperhomocysteinemia is considered a possible contributor to the complex pathology of Alzheimer’s disease (AD). For years, researchers in this field have discussed the apparent detrimental effects of the endogenous amino acid homocysteine in the brain. In this study, the roles of hyperhomocysteinemia driven by vitamin B deficiency, as well as potentially beneficial dietary interventions, were investigated in the novel AppNL-G-F knock-in mouse model for AD, simulating an early stage of the disease. Methods: Urine and serum samples were analyzed using a validated LC-MS/MS method and the impact of different experimental diets on cognitive performance was studied in a comprehensive behavioral test battery. Finally, we analyzed brain samples immunohistochemically in order to assess amyloid-β (Aβ) plaque deposition. Results: Behavioral testing data indicated subtle cognitive deficits in AppNL-G-F compared to C57BL/6J wild type mice. Elevation of homocysteine and homocysteic acid, as well as counteracting dietary interventions, mostly did not result in significant effects on learning and memory performance, nor in a modified Aβ plaque deposition in 35-week-old AppNL-G-F mice. Conclusion: Despite prominent Aβ plaque deposition, the AppNL-G-F model merely displays a very mild AD-like phenotype at the investigated age. Older AppNL-G-F mice should be tested in order to further investigate potential effects of hyperhomocysteinemia and dietary interventions.
Pathogenic variants in PRRT2, encoding the proline-rich transmembrane protein 2, have been associated with an evolving spectrum of paroxysmal neurologic disorders. Based on a cohort of children with PRRT2-related infantile epilepsy, this study aimed at delineating the broad clinical spectrum of PRRT2-associated phenotypes in these children and their relatives. Only a few recent larger cohort studies are on record and findings from single reports were not confirmed so far. We collected detailed genetic and phenotypic data of 40 previously unreported patients from 36 families. All patients had benign infantile epilepsy and harbored pathogenic variants in PRRT2 (core cohort). Clinical data of 62 family members were included, comprising a cohort of 102 individuals (extended cohort) with PRRT2-associated neurological disease. Additional phenotypes in the cohort of patients with benign sporadic and familial infantile epilepsy consist of movement disorders with paroxysmal kinesigenic dyskinesia in six patients, infantile-onset movement disorders in 2 of 40 individuals, and episodic ataxia after mild head trauma in one girl with bi-allelic variants in PRRT2. The same girl displayed a focal cortical dysplasia upon brain imaging. Familial hemiplegic migraine and migraine with aura were reported in nine families. A single individual developed epilepsy with continuous spikes and waves during sleep. In addition to known variants, we report the novel variant c.843G>T, p.(Trp281Cys) that co-segregated with benign infantile epilepsy and migraine in one family. Our study highlights the variability of clinical presentations of patients harboring pathogenic PRRT2 variants and expands the associated phenotypic spectrum.
Iron deprivation activates mitophagy and extends lifespan in nematodes. In patients suffering from Parkinson’s disease (PD), PINK1-PRKN mutations via deficient mitophagy trigger iron accumulation and reduce lifespan. To evaluate molecular effects of iron chelator drugs as a potential PD therapy, we assessed fibroblasts by global proteome profiles and targeted transcript analyses. In mouse cells, iron shortage decreased protein abundance for iron-binding nucleotide metabolism enzymes (prominently XDH and ferritin homolog RRM2). It also decreased the expression of factors with a role for nucleotide surveillance, which associate with iron-sulfur-clusters (ISC), and are important for growth and survival. This widespread effect included prominently Nthl1-Ppat-Bdh2, but also mitochondrial Glrx5-Nfu1-Bola1, cytosolic Aco1-Abce1-Tyw5, and nuclear Dna2-Elp3-Pold1-Prim2. Incidentally, upregulated Pink1-Prkn levels explained mitophagy induction, the downregulated expression of Slc25a28 suggested it to function in iron export. The impact of PINK1 mutations in mouse and patient cells was pronounced only after iron overload, causing hyperreactive expression of ribosomal surveillance factor Abce1 and of ferritin, despite ferritin translation being repressed by IRP1. This misregulation might be explained by the deficiency of the ISC-biogenesis factor GLRX5. Our systematic survey suggests mitochondrial ISC-biogenesis and post-transcriptional iron regulation to be important in the decision, whether organisms undergo PD pathogenesis or healthy aging.
Теорія напівосвіти Адорно була вперше представлена як доповідь на З’їзді німецьких соціологів (1959). В ній розглядаються тенденції, що відбуваються у сучасній освіті і обумовлюють її кризу, яка загострюється у соціокультурних контекстах пізнього капіталізму. Теорія напівосвіти переосмислює і актуалізує концептуалізації освіти та культури у німецькій класичній філософії, марксизмі і фройдизмі, розкриваючи діалектику просвітництва через діагностику спотворень і деформацій освіти в опціях відчуженого духа, що криє у собі небезпеку ліквідації культури, яка перетворюється на масову, і руйнації людського буття через інструменталізацію свідомості та примусову адаптацію. Напівосвіта паразитує на ідеї освіти, яка є внутрішньо суперечливою через поєднання настанов на автономію та адаптацію. Подолання цієї суперечності можливе через негативну діалектику, яка комплементарно поєднує критику суспільства і критику освіти, відкриваючи для них нові горизонти
Mobile genetic elements (MGEs), especially multidrug-resistance plasmids, are major vehicles for the dissemination of antimicrobial resistance determinants. Herein, we analyse the MGEs in three extensively drug-resistant (XDR) Klebsiella pneumoniae isolates from Germany. Whole genome sequencing (WGS) is performed using Illumina and MinION platforms followed by core-genome multi-locus sequence typing (MLST). The plasmid content is analysed by conjugation, S1-pulsed-field gel electrophoresis (S1-PFGE) and Southern blot experiments. The K. pneumoniae isolates belong to the international high-risk clone ST147 and form a cluster of closely related isolates. They harbour the blaOXA-181 carbapenemase on a ColKP3 plasmid, and 12 antibiotic resistance determinants on an multidrug-resistant (MDR) IncR plasmid with a recombinogenic nature and encoding a large number of insertion elements. The IncR plasmids within the three isolates share a high degree of homology, but present also genetic variations, such as inversion or deletion of genetic regions in close proximity to MGEs. In addition, six plasmids not harbouring any antibiotic resistance determinants are present in each isolate. Our study indicates that genetic variations can be observed within a cluster of closely related isolates, due to the dynamic nature of MGEs. The mobilome of the K. pneumoniae isolates combined with the emergence of the XDR ST147 high-risk clone have the potential to become a major challenge for global healthcare.
Photorhabdus and Xenorhabdus bacteria live in a highly specific symbiosis with nematodes that belong to the genus of Heterorhabditis and Steinernema, respectively. These cruiser type nematodes actively search for soil-dwelling insects and infect them via natural openings. Inside of the insect, the bacteria are released into the hemocoel where they start producing an array of secondary metabolites to bypass the insect immune system and kill the prey within 48 hours. Many of those natural products possess bioactivities against other bacteria, fungi, protozoa or insects, which makes them interesting candidates for pharmaceutical applications. Even though advanced molecular biological methods in combination with bioinformatics tools can now be used to predict biosynthetic gene clusters (BGCs) and their products, there are still many BGCs with unknown products. Even for the plethora of natural products that were successfully identified in the last couple of years, the exact ecological function often remains elusive, as laboratory conditions can vary considerably from the natural environment of the bacteria. Knowledge about the natural conditions that stimulate, or repress production of certain natural products and their underlying regulatory mechanisms yield new approaches for natural product research and enables possibilities for selective manipulations of the regulatory cascades.
The overarching goal of this work was to examine the regulatory networks in Photorhabdus and Xenorhabdus strains. The first part of this work focused on the Hfq-dependent regulation of specialized metabolite production. In those genera, the RNA chaperone, Hfq, represses expression of hexA, which encodes for a global transcriptional regulator that acts as the master repressor for SM production. Multiple global approaches were used to identify the sRNA ArcZ, which targets a specific region in the 5’-untranslated region of the hexA mRNA and ultimately guides Hfq in order to repress its expression. It was shown that a deletion of arcZ led to a drastic reduction of SM production in Photorhabdus and Xenorhabdus, consistent with the phenotype of their respective hfq deletion mutants. Transcriptomic profiling revealed far-reaching effects on the transcriptome, with up to 735 coding sequences significantly affected in the arcZ deletion strain. Finally, it was shown that the resulting chemical background, devoid of SMs, in combination with targeted promotor exchange can be used to exclusively overproduce a desired natural product, representing an alternative route of genetic manipulation.
The second part of this work focused on the influence and identification of insect related compounds that affect SM production in P. laumondii, X. szentirmaii and X. nematophila. Insect homogenate was generated from G. mellonella larvae, a model host for these bacteria. Supplementation of the cultivation medium with homogenate induced considerable shifts in the SM profiles of those bacteria. A global effect on the transcriptional output was determined by transcriptomic profiling. The core response to the simulation of an insect environment consisted of ten CDS, eight of which are involved in the degradation of fatty acids or the import of maltose and maltodextrin into the cells. Two abundant components in the insect homogenate, trehalose and putrescin, were added to the cultivation medium of those strains and subsequent HPLC-MS analysis revealed a direct correlation of their concentration in the medium and the production titres of certain SMs. These results indicated that the bacteria sense the insect environment via different insect specific components in order to initiate a metabolic adjustment, which is probably required for adaptation to the insect host.
The last part of this work examined the influence of other, so far not directly related genes on SM production, based on the isolation of P. laumondii transposon-insertion mutants with clear phenotypic alterations. Re-sequencing and SM profiling of the mutant strains revealed that a transposon-insertion in the gene encoding for a putative DNA-adenine methyltransferase affected SM production. The phenotype was confirmed by deleting this gene. Based on Single-Molecule Real-Time sequencing, the complete methylome of the WT, deletion- and complementation mutant were analysed (experimental work performed by Sacha J. Pidot, Melbourne, Australia). No obvious alterations were detected in the methylation patterns of the strains, indicating that the dam gene product does not methylate the adenine in GATC-motifs, as it was described in literature for E. coli. This data raises the question what the function of the putative DNA-adenine methyltransferase is in P. laumondii and how it can influence the secondary metabolism. Even though there is currently no clear evidence, the potential role of epigenetic gene regulation mechanisms should be considered in further work.
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.