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Elucidating the Singlet Fission Mechanism with Time-Resolved Multi-Dimensional Spectroscopies
No full textSinglet fission (SF) can enhance light-conversion efficiencies by splitting high-energy photons
into multiple low-energy triplet excitons, preserving otherwise lost energy due to thermalization.
This can potentially improve efficiencies by 30% relative to the Shockley-Queisser limit in
single-junction solar cells, driving extensive research into suitable sensitizer materials. A
bottleneck of research is that strong coupling promotes efficient SF but also hinders separation
of generated triplets. Striking just the right balance is challenging, due to the multitude of
factors that may affect the sensitizers’ SF capabilities. Moreover, the presence of multiple dark
states in the initial stages of SF complicates its experimental evaluation in regards to those
critical factors.
This thesis aims to address these challenges by studying the impact of targeted system
modifications on the SF mechanism under weak coupling conditions using time-resolved
spectroscopic methods, such as transient absorption (TA) and two-dimensional electronic
spectroscopy (2DES). For example, the feasibility of intermolecular SF is studied in a
pentacene derivate, where acene faces are shielded with additional phenylene functional
groups that restrict interaction between chromophores. While SF is not observed in solution,
thin films of the materials dispersed in polymer matrices show SF rates (kSF) that follow a
Förster resonance energy transfer (FRET) scaling with the average chromophore separation
(R): kSF ∝ R-6
. In turn, the excitation-energy transfer (EET) mechanism acts as the rate-limiting
step to SF and enhances it in a similar fashion to how natural light-harvesting networks improve
energy flow in proteins: Singlet excitons are funneled by FRET to SF-reaction sites where it
can proceed with near-unity quantum yields.
More attention is directed towards intramolecular SF (i-SF) in spiro-linked dimers, consisting
of two modifiable chromophores covalently bound to a spiro-carbon linker. Through spectral
reconstruction and semi-classical simulations of 2DES signal responses, it is shown that the
linker provides a framework of weak coupling that is still strong enough to enable efficient i-SF.
Dimerization of two dissimilar chromophores into heterodimers finely and predictively tunes
the energetic driving force of i-SF, which shown to have a great impact on its rate and
efficiency. Hetero-oligomerization proves especially effective in furnishing i-SF sensitizers that
show improved triplet yields (≈174% yield for separated triplets) compared to their homodimeric counterparts, facilitated also by downhill EET. Direct control over the excitonic coupling
responsible for i-SF is achieved by additionally linking the individual chromophores via
molecular bridges; by modulating the dihedral geometry of chromophores, the strength of their
intramolecular coupling is directly affected. How this chemical modification translates to
changes in the excitonic coupling, and in turn, the i-SF process, is evaluated experimentally
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using transient 2DES, which was implemented during this work. Through this advanced
spectroscopic method, a primarily direct i-SF mechanism is concluded for when chromophores
are in closer proximity. As the chromophores are further separated by insertion of molecular
bridges, direct i-SF becomes increasingly suppressed in favor of a super-exchange mediated
i-SF mechanism and the overall rate and efficiency of the excited-state process decreases.
Obtaining such high levels of mechanistic detail is usually reserved to theoretical studies, which
has been made possible by utilizing the extraordinaire selectivity of transient 2DES towards
excited state transitions, opening up the avenue to study SF or other excited-state phenomena
with unprecedented detail. Altogether, this thesis lays out the impact of excitonic coupling
(through dimer geometries), energetic driving force (through alterations of chemical
compositions), and excitation energy transfer on the outcome of singlet fission, understood
through the lens of multiple time-resolved spectroscopies. As demonstrated here, these
properties of nature act synergistically and can be utilized to improve the efficiency of (i-) SF,
providing insight into molecular design principles for organic materials intended for applications
in solar energy technologies
TIR-domain-containing protein C of uropathogenic E. coli CFT073 as a modulator of innate immune checkpoints
No full textUrinary tract infections are one of the most common community-acquired infections worldwide, affecting approximately 150 million people each year. Uropathogenic E. coli are responsible for the vast majority of UTIs. In order to infect the lower and upper urinary tract, they express a wide variety of virulence factors. One of these virulence factors is TcpC, a Toll/interleukin-1 receptor domain-containing protein produced by various E. coli strains of the phylogenetic group B2, including CFT073. Studies have shown that TcpC is able to inhibit TNFα and IL-1β release of mouse macrophages during an infection with E. coli CFT073. It is suggested that TcpC is able to inhibit cytokine release of these cells by binding to specific proteins of the TLR4 signaling cascade and the NLRP3 inflammasome.
I now report that TcpC is able to stimulate cytokine release of immune and bladder epithelial cells during infection. Human monocytes and human bladder epithelial cells release higher amounts of proinflammatory cytokines after infection with TcpC-producing CFT073 strains compared to a TcpC knockout. Differentiation of monocytes to macrophages abrogates this TcpC-dependent effect. Infection of T24/83ΔTLR4 cells suggests that exclusively TLR4 is responsible for a proinflammatory reaction. Furthermore, infection of T24/83ΔMyD88 bladder epithelial cells suggests that the TcpC-induced stimulation of proinflammatory cytokines is MyD88-independent. THP-1 cells treated with conditioned medium in which TcpC was overexpressed at different levels showed that TcpC inhibited cytokine release after stimulation with LPS plus ATP at low levels of induction. Deletion of the TIR-domain of TcpC leads to a loss of the inhibitory capabilities, showing that it is crucial for the function of the protein in this context.
Thus, during an infection of monocytes with CFT073, the proinflammatory response is increased compared to the TcpC knockout strain, whereas treatment with culture supernatants containing TcpC inhibits the proinflammatory response of LPS plus ATP stimulated monocytes. In summary, I conclude that the TcpC-induced inhibition versus stimulation of release of proinflammatory cytokines may depend on the direct contact between CFT073 and eukaryotic cells. Since TcpC is able to bind to TLR4 and MyD88, I think it affects myddosome formation after stimulation of cells with LPS, which may be further influenced by the direct contact of the bacterium with the immune cells
Nietzsches nihilistische Ontologie
No full textIm Frühjahr 1887 zeichnet Friedrich Nietzsche den folgenden Gedanken auf: „Dem Werden den Charakter des Seins aufzuprägen – das ist der höchste Wille zur Macht.“ Handelt es sich hierbei um eine, gar die grundlegende ontologische Einsicht des Philosophen, um die entscheidende Verhältnis-bestimmung zwischen Sein, Werden und Wille zur Macht? Welchen Status und Rang besitzt die Charakterlehre im Hinblick auf Sein und Werden, Denken und Realität, Wille zur Macht und Ewige Wiederkunft, Wert und Nihilismus? Es ist vielversprechend, den Aussagen der Notiz nachzugehen, ihrer Vorgeschichte, ihren Hintergründen, Voraussetzungen, Beziehungen und Konsequenzen, ihrem Gewicht und den Fragen, die sich aus ihnen ergeben
Spatial multi-omics profiling of host-microbiome interactions in primary colorectal tumors
No full textThe tumor microenvironment (TME) of colorectal cancer (CRC) represents a complex ecosystem, encompassing tumor, immune, stromal, and bacterial components. Prior research highlighted the significant impact of these interactions on CRC clinical manifestation
and treatment outcome. However, a substantial gap remains in omics datasets capable of capturing these interactive networks comprehensively, a challenge often attributed to the technical difficulties in achieving balanced recovery of all cellular entities
within CRC tissues.
This dissertation introduces innovative experimental methodologies and frameworks designed to generate detailed data from primary CRC resections, encompassing both host tissue and its local bacterial populations. By developing and implementing Host-Microbe RNA-sequencing (HMR-seq) technique in a newly established cohort of 47 CRC patients, I identified transcriptional alterations within CRC tissues, mirrored by compositional shifts in tumor-resident bacteria. Joint host-microbiome analyses identified significant associations between intratumoral bacteria and oncogenic and immune-related gene expression signatures, with distinct configuration in MSI and MSS tumor subtypes.
Furthermore, spatial and single-cell transcriptomics analyses uncovered distinct gene expression landscapes across CRC tissues, especially within immune cell populations. These spatial gene expression variances were shaped by genetic backgrounds and were further delineated by regional differences between patient-matched tumor core and invading front sections. This emphasizes spatial organization as a key factor in intratumoral heterogeneity. Additionally, spatial assessments utilizing m-HybISS for microbiome in
situ profiling revealed that intratumoral bacteria also displayed varied localization patterns and densities, influenced by the histopathological characteristics of assayed MSI and MSS tumor sections.
Overall, the methodologies and multi-omics dataset presented in this work offer valuable toolkits for dissecting host-microbe interactions within primary CRC resections. The insights reported herein hold promise for broadening our understanding of host-microbe interactions in CRC and may inform therapeutic strategies for this and potentially other solid tumors influenced by microbiome interactions
Modeling Malaria Parasite Motility: From Chiral Active Particles to Complex Shapes with Surface Flow
No full textActive matter taps local energy sources to generate forces and motion. A key example is the locomotion of microorganisms, which can be modeled as active Brownian particles. A particularly intriguing case involves chiral active particles that follow a preferred sense of rotation. Working across relevant scales, I show theoretically that malaria parasites, owing to their high speeds and curved shape, provide an excellent model system for this class.
First, I built an automated image-processing pipeline to analyze experimentally measured trajectories in a three-dimensional hydrogel.
This established proof of uniformly right-handed chirality, which also controls transitions between two- and three-dimensional environments.
I then formulated a stochastic theory for chiral active particles based on an Ornstein–Uhlenbeck process for rotational dynamics, demonstrating that helical motion is more robust to fluctuations and can, statistically, yield larger net displacements—so that a helix can be ``straighter than a straight line”.
Finally, I developed a theory for the self-organized surface flow of adhesins, driving the motion. This suggested that the parasites’ curved shape is an evolutionary adaptation to avoid on-the-spot rotations. An extension of the theory that incorporates mechanical deformations attributes the observed right-handedness to an asymmetric release of adhesion molecules; this prediction was corroborated experimentally
Der datenschutzrechtliche Auskunftsanspruch im Anstellungsverhältnis: Inhalt – Grenzen – Durchsetzung – Sanktionen
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Nuclear quantum dynamics driven by X-ray free-electron lasers
No full textMössbauer spectroscopy is well established across the natural sciences. The exceptionally narrow linewidths of Mössbauer nuclei also make them a promising platform for x-ray quantum optics. Several fundamental quantum-optical phenomena, including electromagnetically induced transparency and superradiance, have already been demonstrated. Yet for decades, the same narrow linewidth restricted experiments at synchrotrons to the low-excitation regime, with on average less than one resonant photon per pulse. This limitation changed with the advent of X-ray free-electron lasers (XFELs), which deliver orders of magnitude more photons than synchrotrons. As a result, pulses containing multiple resonant photons occur frequently, enabling experiments previously not possible. In this thesis, we present several first-of-their-kind XFEL-experiments conducted within our collaborations. We demonstrate the x-ray excitation of the 45 Sc nuclear clock transition, introduce and apply a single-shot analysis to Mössbauer time-domain data, and investigate unexpected signals observed in nuclear resonant scattering with XFELs. Additionally, we simulate the de-excitation dynamics of a
nuclear ensemble. Besides establishing a suitable simulation scheme, we focus on non-linear effects arising from dipole-dipole couplings and non-linear modifications of propagation effects. Together, these results show how the unprecedented intensities of XFELs open a new era for Mössbauer science,
advancing both experiment and theory