22455 research outputs found
Sort by
The potential of immunomodulatory kits to generate leukaemia-derived dendritic cells competent to (re)activate the immune system against leukaemic blasts in acute myeloid leukaemia
Get PDF
Aufklärung der Rolle von zirkulierenden und ortständigen CXCR4+ Zellen im ischämischen Herzen
Get PDFDie vorliegende Arbeit widmete sich der Identifizierung der CXCR4+-Population und ihrer Rolle im postischämischen Herzen. Basierend auf dem gegenwärtigen wissenschaftlichen Kenntnisstand über die SDF1-CXCR4-Achse hat unsere Arbeitsgruppe die Inhibition der Prolylhydroxylase als ein potentielles Therapieziel in Aussicht gestellt. Uns interessierte vor allem die Wirkung eines PHI auf die CXCR4+-Zellpopulation sowie auf die kardiale Pumpfunktion.
In unserer Arbeit konnten wir zeigen, dass unter normoxischen Bedingungen ein Großteil der CXCR4+-Zellen im Knochenmark nachgewiesen werden konnte, während ihre Präsenz im Herzen kaum vorhanden war. Postischämisch haben wir jedoch eine Erhöhung der CXCR4+- Zellen sowohl im Knochenmark als auch im Herzen festgestellt. Durch die Markierung der CXCR4+-Zellen mit dem Oberflächenmarker CD45 konnte ihr Ursprung am ehesten im blutbildenden System des Knochenmarks auf Leukozyten identifiziert werden. Weiterführende FACS-Analysen deuteten auf eine entscheidende Beteiligung der CD11b+Zellpopulation beim kardialen Reparaturprozess hin. Insbesondere konnten wir mit unseren Versuchen zeigen, dass die systemische Applikation des Prolylhydroxylase-Inhibitors DMOG zu einer verstärkten Rekrutierung der CXCR4+-Zellen führte. Diese verstärkte Rekrutierung der CXCR4+-Zellen wurde sowohl durch einen wahrscheinlich effektiveren Verlauf der Entzündungsreaktion als auch durch die parakrinen Effekte der rekrutierten Zellen begünstigt. Als Resultat beobachteten wir eine verbesserte Herzfunktion in der Gruppe der therapierten Tiere
Affect experience in natural language collected with smartphones
Get PDFRecent technological advancements in computerized text and speech analysis as well as machine learning methods have sparked a growing body of research investigating the algorithmic recognition of affect from the ubiquitous digital traces of natural language data and corresponding affect-linked language variations. Also, commercial interest to leverage these new data using AI for affect inferences is on the rise. However, due to the challenges associated with collecting data on subjective affect experience and corresponding language samples, previous research studies and commercial products have mostly relied on data sets from labelled text or enacted speech and, thereby, are focused on affect expression. This work leverages new smartphone-based data collection methods to collect self-reports on in-situ subjective affect experience and corresponding language samples in the wild to investigate between-person differences and within-person fluctuations in affect experience. The present dissertation aims to achieve three goals: (1) to investigate if between-person differences and within-person fluctuations in subjective affect experience are associated with and predictable from cues in spoken and written natural language, (2) to identify specific language characteristics, such as the use of specific word categories or voice parameters, that are associated with and predictive of affect experience, and (3) to analyze the influence of the context of language production on the associations and predictions of affect experience from natural language.
This work is comprised of two empirical studies that analyze self-reports on subjective affect experience and natural language data collected with smartphones. Study 1 investigates predictions of between-person differences and within-person fluctuations in subjective momentary affect experience in more than 23000 speech samples from over 1000 participants in two data sets from Germany and the United States. In contrast to voice acoustics, which contain limited predictive information for affective arousal, state-of-the-art word embeddings yield significant above-chance predictions for affective arousal and valence. Moreover, interpretable machine learning methods are used to identify those voice features (i.e., loudness and spectral features) that are most predictive of affect experience. Finally, the work suggests that affect predictions from voice cues from semi-structured free speech are superior to those from read-out predefined sentences and that the emotional sentiment of the spoken content has no effect on affect predictions from voice cues. Study 2 analyzes patterns in written language data logged through smartphones' keyboards to investigate how between-person differences and within-person fluctuations in affect experience manifest in and are predictable from logged text data across different time frames and communication contexts. From a data set of more than 10 million typed words, features regarding typing dynamics, word use based on word dictionaries, and emoji and emoticon use are computed. From the data, distinct affect-linked language variations across communication contexts (private messaging versus public posting) and time frames (trait, weekly, daily, momentary) are identified (e.g., the use 1st person singular). Predictions of affect experience from machine learning algorithms, however, are not significantly better than chance. Results of this study highlight the challenges of using occurrence-counts, such as word dictionaries, for the assessment of subjective affect experience.
By leveraging novel smartphone-based experience sampling and on-device language data collection in everyday life, the present dissertation shows how characteristics of spoken and written language are associated with and predictive of subjective affect experience. Thereby, this work highlights the utility of smartphones for investigating subjective affect experience in natural language in the wild, overcoming the caveats of prior research methods. Prediction results, however, challenge the optimistic prediction performances reported in prior works on the recognition of affect expression experience. Using statistical methods from the areas of description, prediction, and explanation, the present dissertation also reveals specific affect-linked language characteristics. Finally, results underline the relevance of the context of language production on language characteristics and corresponding affect predictions. The promising applications and potential future directions of this technology come with multiple challenges with regard to the conceptualization of affect, interdisciplinarity, ethics, and data privacy and security. If these challenges can be overcome, natural language analysis based on data collected with smartphones represents a promising tool to monitor affective well-being and to advance the affective sciences
Phosphorylation of PFKL regulates glycolysis in macrophages following pattern recognition receptor activation
Get PDFTowards multifunctional device concepts utilizing light absorption and charge storage in carbon nitrides
Get PDFThis thesis comprises 5 parts. In Part 1, we start in Chapter 1 by giving a general introduction which includes a motivation (Section 1.1), an introduction into carbon nitrides as the main material class we utilize (Section 1.2), and an overview of important concepts from the field of energy conversion, energy storage, and new device concepts beyond energy storage (respective Section 1.3, Section 1.4, and Section 1.5). Since solar batteries are a multidisciplinary research endeavor that require input from very different research field directions, it is important to have a broad understanding of key concepts. We underline important messages in grey boxes and then proceed in Chapter 2 to underline the fundamental physical and electrochemical background ( Section 2.1 and Section 2.2) as well as electrochemical measurement techniques to characterize the devices (Section 2.3).
Part 2 consists of two perspective papers, which propose fundamental considerations and design guidelines for two emerging research fields: optoionic devices and solar batteries. In our perspective in Chapter 4, we explain the emerging concept of light-assisted ionic effects, which are generally termed optoionic. We start by giving a historical overview over the field and also over related light-ion interaction effects termed photoionic – a term which is used far more often, but only partially relates to optoionics as we understand it today. We then proceed to explain our current understanding of optoionic effects in layered compounds and propose an extension to the picture, that is, the impact of short- or long-range field effects via a case study in carbon nitrides.
Our perspective on solar batteries in Chapter 5 starts by explaining the fundamental Solar Battery Experiment and with this underline how light energy affects the energy and power density as well as operation modes of this new class of devices. We classify two main design routes for the devices: (1) Solar cell and battery can operate in parallel to the consumer and as such the light energy produces a photocurrent that increases the overall current output (IEC). (2) Solar cell and battery can operate in series to the consumer and the photopotential reduces the overall required charging voltage (VEC). We then continue to give an overview and classify all current solar battery designs in the respective category (two or one device designs, the latter with bifunctional electrodes or bifunctional materials) and explain how the respective electrochemical signature of the devices can be understood.
We proceed in Part 3 to discuss the main three research projects associated to this thesis, namely optical design and proof-of-concept device of a solar battery and a photomemristive sensing concept. We start in Chapter 6 with a theoretical study of how to design an integrated solar battery with KPHI acting as photoanode (i.e., light absorber and electron storage electrode) and all-organic polymer hole transport and hole storage materials, with the hole transporter acting as battery electrolyte as well as performing photogenerated hole transfer via a rectified redox ladder-type charge transfer mechanism. We first design an optical model of the device and calculate optimized respective layer thicknesses and illumination geometries (front or rear illumination; light absorption with a high internal quantum efficiency occurring only in a small collection layer at the junction of KPHI and hole transporter) by using charging time as a figure of merit. We conclude that rear illumination significantly reduces parasitic absorption of parts of KPHI not participating in light absorption and thus increases the photocurrent. We then propose several optimization strategies to enhance light absorption in the collection layer: via scattering of a random textured surface, diffraction by quasi-random binary gratings, diffraction of arrays of dielectric nanoparticles, or excitation of localized surface plasmons in metal nanoparticles. We then simulate how light absorption improves energy and power density in a Ragone plot – up to 60 % increase in energy output. The latter is based on a study of photochromic effects as well as the effect of a charging state dependent photocurrent (i.e., the more the battery is charged, the smaller the photocurrent gets) – the latter required an electrochemical study of the photoanode and cathode half cells.
We proceed in Chapter 7 to design a proof-of-concept device by using the knowledge gained from the previous chapter. We start by designing the multilayer configuration of the device, which required a thorough study of thick KPHI film preparation via dip coating and hole transport / hole storage film fabrication via spin coating, as well as an electrochemical study to underline the material's suitability for the desired charge transfer and charge storage dynamics at respective junctions and in the bulk of the layers. We have then performed a study of charging solely via illumination, either when operated as a planar heterojunction solar cell (OCP of 0.45 V, maximum power of 0.326 µW/cm, FF of \num{0.73), or when charged in open circuit conditions and subsequently discharged in the dark with an applied discharging current, i.e., solar battery operation. We analyzed the latter in regard to charge, energy, and power output as a function of illumination time (after illumination of 10000 s: extracted charge of 1.5 mAh/g and energy of 0.60 Wh/kg) and electric discharging current (most efficient operation at smallest current of 5.25 mA/g). We then proceeded to investigate further solar battery modes with an applied current during charging: (1) Both charging and discharging in the dark, (2) charging under illumination, or (3) charging and discharging under illumination. We concluded with looking at how light modifies charge output, electric coulombic efficiency, and Ragone plots. Illumination can yield an increase in extracted energy and charge by 94.1 % and 243 %, respectively.
In Chapter 8, we use knowledge gained throughout this thesis on light charging dynamics of KPHI (i.e., optoionic and optoelectronic properties) to modify the photogenerated hole extraction mechanism. Herein, we sacrificially oxidize organic electron donor molecules, which serve as the analyte in an electrolyte, and quantitatively relate the change in photophysical properties accompanying KPHI charging to the amount of analyte. Thus, this device can be understood as a sensor, which senses via charge storage, and thereby imparting a memory function to this electrochemical sensor. Different operations occur: (1) Charging of the sensor "writes" the concentration information onto the device. (2) Reading is performed via different electrochemical and optical techniques. (3) Resetting occurs by quenching the charging state with the sacrificial electron acceptor oxygen. We term this sensor a photomemristive sensor, since electrochemical properties such as resistance depend on the charging history. Note that KPHI acts simultaneously as receptor, transducer, and memristive amplifier. We start this work by underlining KPHI's photoelectrochemical amperometric sensing ability with manifold analytes (sugars, alcohols, ascorbic acid, dopamine), with glucose showing a LOD of 11.4 µM. We then proceed to investigate charging as a function of illumination time and use glucose as a case study analyte. Readout is performed by evaluating the change in OCP (Potentiometric sensing), resistance (Impedimetric sensing), charge (Coulometric sensing), radiative emission (Fluorometric sensing), and change in color (Colorimetric sensing) – all readout methods showing different levels of invasiveness, readout times (instant to <300 s), and sensing over a wide range of concentrations (up to 50 µM to 50 mM).
In Part 4 and Part 5, we conclude with a conclusion and outlook towards new research/application directions as well as appendices consisting of the supporting information of Chapter 6, Chapter 7, and Chapter 8
Understanding collective adaptation to climate change in socio-culturally diverse contexts
Get PDFThe intensifying and more frequent impacts of climate change, coupled with unequal urban development, require more dedicated and integrated approaches to adaptation. Recognizing climate change as a collective action problem necessitates a shift for researchers and policymakers, moving from focusing solely on individual needs and capacities to a more social perspective. This shift is most urgently needed in highly exposed and vulnerable coastal cities, where climate change already has severe impacts. To effectively address future adaptation needs, understanding local visions, needs, and capacities related to climate change adaptation is imperative. This entails considering another characteristic of these particular high-risk locations that has been rather neglected in the research on climate change adaptation so far. Socio-cultural diversity significantly influences risk perceptions, vulnerabilities, and behaviors, thereby shaping the formation of social groups and their behaviors in response to climate change. Despite some academic attention to the psychological influences on (collective) climate change adaptation, empirical evidence as well as theoretical and conceptual debates are lacking – especially for socio-culturally diverse contexts like cities.
With this study, I aim to address these gaps by conceptually and empirically examining the phenomenon of collective adaptation in socio-culturally diverse, high-risk contexts. Therefore, this study will answer several pertinent research questions: Is there evidence for collective adaptation? Which groups form to adapt collectively? What motivates them to become and stay actively engaged in collective adaptation? And if and how do differently adapting groups interact?
I apply a mixed-method approach combining deductive and inductive methods to develop a comprehensive framework that conceptualizes the emergence of collective adaptation in socio-culturally diverse contexts from a social psychology perspective. The framework covers the entire collective adaptation process encompassing the development of risk-based social identities, their materialization into groups, their activation, and potential types of adaptation in socio-culturally diverse settings.
I empirically tested and validated the framework through data from Jakarta, the highly exposed, urbanized, and socio-culturally diverse capital city of Indonesia. Through semi-structured interviews, expert elicitations, and a representative survey of kampung cooperatives – a collective phenomenon in high-risk neighborhoods in Jakarta – I examine the validity of the three sequences of the developed conceptual framework. The results provide evidence for the socio-cultural diversity among the most vulnerable. Furthermore, I am able to demonstrate that in the face of climate risk, only three out of many social identities become salient in highly exposed and diverse neighborhoods in Jakarta. Materialized into groups and networks, they largely differ in their collective adaptation capacities. The results also indicate that the materialization of identities into groups is insufficient for explaining their collective actions, given a high share of inactive group members. Against this background, the study identifies a set of temporally differentiated motivating factors. Initial triggers motivate group members to start becoming active; long-term motivators keep them engaged over time. A few identified general facilitators contribute to both, the initial activation as well as long-term engagement. Lastly, the developed conceptual framework illustrates that the interaction of differently adapting groups is mediated by multiple influencing factors which ultimately affect urban adaptation patterns.
While the empirical findings and their implications are mostly relevant for Jakarta or very similar cultural contexts in which social trust, reciprocity, and mutual support are strong societal values, the more abstract conceptual framework for collective adaptation is applicable more broadly. It is based on underlining socio-psychological factors that influence engagement in collective adaptation and is hence independent of varying context conditions.
Overall, this study expands the current knowledge on collective adaptation in multiple ways. The conceptual framework and its sequences address the lacking theoretical and conceptual discussions around the topic. It also represents a valuable analytical lens and can guide future scientific work on collective adaptation as its sequences can be well operationalized, informing data collection and analysis. At the same time, the empirical findings resulting from the application of the conceptual framework differentiate the current understanding of urban adaptation to climate change in Southeast Asian coastal cities, particularly in terms of soft adaptation options, heterogeneous collective capacities to adapt, and collective adaptation actions. It emphasizes the importance of considering socio-cultural differences and diversity in shaping adaptation behaviors and interactions. Both, the conceptual and the empirical insights are also valuable for policy development and the practical facilitation of socially just urban adaptation strategies
The Role of Raf-1 and B-Raf in B cell activation, differentiation, and tumorigenesis in mice
Get PDFB cells are part of the adaptive immune system and, as plasma cells, fight various path-ogens by producing antibodies. The development, homeostasis, and self-tolerance of B cells are regulated by several key cellular processes. These cellular key functions, as proliferation, differentiation, but also apoptosis and cell cycle arrest are controlled by different signaling pathways. One major regulator of these processes is the extracellular signal–regulated kinase (ERK), which is mainly activated by the mitogen-activated pro-tein kinase (MAPK) pathway Ras-Raf-MEK-ERK. In B cells, the contribution of the Ras-Raf-MEK-ERK signaling pathway to B cell development, activation, differentiation, and transformation was described by the analyses of the components Ras and ERK in different cell lines.
To investigate the role of the Raf-kinases on these processes specifically in primary murine B cells, Raf-1fl/fl//B-Raffl/fl//mb1-Cre+/- (DKO) mice were generated leading to the B cell specific deletion of the two kinases from the early B cell development onwards. This mouse model was used within this thesis to analyze Raf mediated functions during B cell development, activation, and differentiation. Within this dissertation, important roles of B-Raf and Raf-1 in the following processes was revealed: (I) B-Raf and Raf-1 were not required to mediate ERK phosphorylation in BCR, LPS and CD40 stimulated B cells but rather acted as negative regulators of PI3K or Rac/PAK mediated ERK phos-phorylation in resting and activated mature B cells. (II) Inactivation of B-Raf and Raf-1 in DKO mice resulted in an impaired T independent immune response. (III) B-Raf//Raf-1 inactivation caused a block in plasma cell differentiation at the transition of activated B cells to pre-plasmablasts and in their further differentiation into plasmablasts. We found that at this stages B-Raf and Raf-1 mediate a strong increase in ERK phosphorylation, which seemed to be essential for plasma cell differentiation.
Furthermore, Raf-1fl/fl//B-Raffl/fl//LMP1/CD40flSTOP+/-//CD19-Cre+/- (RafDKO/LC40) mice were compared with LMP1/CD40flSTOP+/-//CD19-Cre+/- (LC40) and control mice to ex-amine the effect of the genetic inactivation of B-Raf and Raf-1 on B cells with a consti-tutively active CD40 signal and the resulting LC40 driven B cell transformation. Inactiva-tion of B-Raf and Raf-1 in RafDKO/LC40 mice decreased the LC40 mediated pheno-type of B and T cell expansion and B cell transformation. As revealed by an RNA-Seq analysis, this appeared to be predominantly caused by decreased LC40 mediated Myc expression, and reduced Notch2 and non-canonical NFκB activation. These data, sug-gest that Raf-kinases modulate the activation of these two signaling pathways down-stream of CD40.B-Zellen sind Teil des adaptiven Immunsystems und bekämpfen als Plasmazellen durch Antikörperproduktion verschiedene Krankheitserreger. Die Entwicklung, Homöo-stase und Selbsttoleranz von B-Zellen werden durch mehrere zelluläre Schlüsselpro-zesse reguliert. Diese umfassen Proliferation, Differenzierung, aber auch Apoptose und Zellzyklusarrest und werden durch verschiedene Signalwege gesteuert. Ein wichtiger Regulator dieser Prozesse ist die extrazelluläre signalregulierte Kinase (ERK), die hauptsächlich durch den Mitogen-aktivierten Proteinkinase (MAPK)-Signalweg Ras-Raf-MEK-ERK aktiviert wird. In B-Zellen wurde der Beitrag des Ras-Raf-MEK-ERK-Signalwegs zur Entwicklung, Aktivierung, Differenzierung und Transformation von B-Zellen durch die Analyse der Komponenten Ras und ERK in verschiedenen Zelllinien beschrieben.
Um die Rolle der Raf-Kinasen auf diese Prozesse speziell in primären murinen B-Zellen zu untersuchen, wurden Raf-1fl/fl//B-Raffl/fl//mb1-Cre+/- (DKO)-Mäuse erzeugt. Diese weisen eine B-Zell-spezifischen Deletion der beiden Kinasen ab der frühen B-Zell-Entwicklung auf. Dieses Mausmodell wurde in dieser Arbeit verwendet, um die Raf-vermittelten Funktionen während der B-Zellentwicklung, -aktivierung und -differenzierung zu analysieren. Im Rahmen dieser Dissertation wurden wichtige Rollen von B-Raf und Raf-1 in den folgenden Prozessen aufgedeckt: (I) B-Raf und Raf-1 wa-ren nicht erforderlich, um die ERK-Phosphorylierung in BCR-, LPS- und CD40-stimulierten B-Zellen zu vermitteln, sondern fungierten vielmehr als negative Regulato-ren der PI3K- oder Rac/PAK-vermittelten ERK-Phosphorylierung in ruhenden und akti-vierten reifen B-Zellen. (II) Die Inaktivierung von B-Raf und Raf-1 in DKO-Mäusen führ-te zu einer beeinträchtigten T-Zell unabhängigen Immunantwort. (III) Die B-Raf//Raf-1-Defizienz verursachte eine Blockade der Plasmazell-Differenzierung beim Übergang von aktivierten B-Zellen zu Prä-Plasmablasten und bei ihrer weiteren Differenzierung zu Plasmablasten. Wir fanden heraus, dass B-Raf und Raf-1 in diesen Stadien einen star-ken Anstieg der ERK-Phosphorylierung bewirken, der für die Plasmazell-Differenzierung wesentlich zu sein scheint.
Darüber hinaus wurden Raf-1fl/fl//B-Raffl/fl//LMP1/CD40flSTOP+/-//CD19-Cre+/- (RafD-KO/LC40)-Mäuse mit LMP1/CD40flSTOP+/-//CD19-Cre+/- (LC40)- und Kontrollmäusen verglichen, um die Auswirkungen einer genetischen Inaktivierung von B-Raf und Raf-1 auf B-Zellen mit einem konstitutiv aktiven CD40-Signal und die daraus resultierende LC40-getriebene B-Zelltransformation zu untersuchen. Die Inaktivierung von B-Raf und Raf-1 in RafDKO/LC40-Mäusen verringerte den LC40-vermittelten Phänotyp der B- und T-Zell-Expansion sowie der B-Zelltransformation. Wie eine RNA-Seq-Analyse ergab, scheint dies in erster Linie auf eine verringerte LC40-vermittelte Myc-Expression und eine reduzierte Notch2- und nichtkanonische NFκB-Aktivierung zurückzuführen zu sein. Diese Daten deuten darauf hin, dass Raf-Kinasen die Aktivierung dieser beiden Signalwege stromabwärts von CD40 modulieren