Time-resolved broadband Raman spectroscopies; A unified six-wave-mixing representation

Excited-state vibrational dynamics in molecules can be studied by an electronically off-resonant Raman process induced by a probe pulse with variable delay with respect to an actinic pulse. We establish the connection between several variants of the technique that involve either spontaneous or stimulated Raman detection and different pulse configurations. By using loop diagrams in the frequency domain we show that all signals can be described as six wave mixing which depend on the same four point molecular correlation functions involving two transition dipoles and two polarizabilities and accompanied by a different gating. Simulations for the stochastic two-state-jump model illustrate the origin of the absorptive and dispersive features observed experimentally

Broadband infrared and Raman probes of excited-state vibrational molecular dynamics; Simulation protocols based on loop diagram

Vibrational motions in electronically excited states can be observed by either time and frequency resolved infrared absorption or by off resonant stimulated Raman techniques. Multipoint correlation function expressions are derived for both signals. Three representations for the signal which suggest different simulation protocols are developed. These are based on the forward and the backward propagation of the wavefunction, sum over state expansion using an effective vibration Hamiltonian and a semiclassical treatment of a bath. We show that the effective temporal ($\Delta t$) and spectral ($\Delta\omega$) resolution of the techniques is not controlled solely by experimental knobs but also depends on the system dynamics being probed. The Fourier uncertainty $\Delta\omega\Delta t>1$ is never violated

Function and Regulation of the Y-Linked Axonemal Dynein Genes During Drosophila Spermatogenesis

The germline is considered to be immortal, meaning an organism’s germ cells have the potential to give rise to all subsequent generations. With so much at stake, the germline goes to great lengths to protect itself while also maintaining reproductive potential, resulting in fascinating and innovative biology. This thesis focuses on two aspects of germ cell development in Drosophila males that appear disadvantageous yet are prevalent across drosophilids. The first is the expression of the Y chromosome gigantic genes – these genes are essential for fertility yet they are riddled with megabases of repetitive DNA. The second is the assembly of the long cilia found within the sperm’s tail – Drosophila have some of the longest sperm in the animal kingdom, yet little is known about how these long cilia are assembled. This thesis will describe the innovations that have allowed germ cells to overcome these challenges and will go on to discuss how these burdens may benefit the fly. In Drosophila, the Y chromosome is largely heterochromatic, encoding only a handful of genes, which are essential for male fertility. Intriguingly, some of these genes are amongst the largest genes identified to date, spanning several megabases. For example, the gene kl-3, which encodes an axonemal dynein motor protein required for sperm motility, spans 4.3Mb with only 14kb of coding sequence. The introns of these genes contain megabases of simple satellite DNA repeats (e.g. (AATAT)n) that comprise over 99% of the locus. Although this “intron gigantism” has been observed in several genes across species, including the mammalian Dystrophin gene, its regulation and functional relevance remains elusive. The transcription/processing of such gigantic genes/RNA transcripts poses a significant challenge. I identified that the Y-linked gigantic genes require a unique gene expression program in order to overcome these challenges. By monitoring Y-linked gene expression over developmental time, I found that transcription of these loci takes 80-90 hours. I further identified two RNA-binding proteins that specifically bind to Y-linked gene transcripts. Loss of either RNA binding protein resulted in sterility due to the loss of Y-linked gene products. I found that this unique gene expression program functions on two fronts: it increases the ability of RNA polymerase to transcribe the repetitive introns, and it aids in processing the large transcripts. I speculate that this program may be utilized to modulate gene expression patterns during development. During Drosophila spermatogenesis, germ cells undergo drastic morphological changes to yield a 1.9mm sperm. The cilia found within the sperm tail are cytoplasmic cilia – a specialized type of cilia where the axoneme (the microtubule structural component) resides within the cytoplasm instead of within a specialized ciliary compartment. Cytoplasmic cilia likely allow for efficient assembly of longer cilia, however, the mechanism for their assembly remains unknown. I found that mRNAs encoding four axonemal dynein heavy chain genes (three of which are Y-linked gigantic genes) colocalize in a novel ribonucleoprotein (RNP) granule, which localizes near the site of axoneme assembly during sperm elongation. Precise localization of this RNP granule mediates incorporation of the axonemal dynein motor proteins into the axoneme. This work is the first to uncover how cytoplasmic cilia are efficiently assembled to allow for the production of 1.9mm sperm, and highlights that there are other cilia assembly mechanisms besides the ancient and conserved mechanism by which traditional cilia assemble.PHDCellular & Molecular BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163043/1/jaclynmf_1.pd

Effectiveness of emotionally focused family therapy (EFFT) in adults experiencing Anorexia Nervosa.

Anorexia nervosa (AN) is one of the most lethal and debilitating psychiatric disorders with a long recovery rate, underscoring the need for efficacious treatment. Although research has made significant advances in individual and systemic treatment options for AN, none have examined the use of family-based treatment options with adults experiencing AN. The following study aims to explore the efficacy of emotionally-focused family therapy (EFFT) in the treatment of AN

Optimale Photochemische Energiekonversion und Umgebungseffekte in Reaktiver Moleküldynamik

One of the main challenges in photochemical energy conversion is the design of charge separating units which are able to generate a long lived charge separated state, and to couple efficiently to an energy storage state. In part I of this work the energy conversion efficiency of a photochemical unit inspired by bacterial photosynthesis is investigated. The developed model is based on non-adiabatic multi step electron transfer to generate a trans-membrane potential gradient. Upon optimization with multi objective genetic algorithms, the biological strategies for high quantum efficiency in photosynthetic reaction centers are derived, which have to suppress loss channels such as charge recombination. The concepts of bacterial photosynthesis are extended to the design of artificial photochemical devices. The unified model consists of a charge separation unit and an energy storing system whereby the coupling between both units is assured by thermal repopulation according to the principle of detailed balance. The complete photosynthetic unit is characterized by the respective current-voltage relation and an upper limit for the overall energy efficiency is derived under AM1.5 global conditions. Such a realistic chemical solar energy conversion system can reach efficiencies, which are comparable to the limits of an ideal single-junction solar cell. In Part II of this work the reactive dynamics of two surrounding controlled photoreactions is investigated on a microscopic scale. In general the effect of the surrounding can be classied into intramolecular contributions, like steric or electronic effects, and intermolecular contributions like the solvent or the embedding in an enzyme. Both limiting cases are examined on the basis of two generic photoreactions. The Dewar DNA lesion follows quantitatively from the 6-4 lesion by UV-A/B irradiation and constitutes the stable end product of continuous solar irradiation. Here the detailed mechanism of the formally 4π-sigmatropic rearrangement is presented, which predicts that only in the (6-4) dinucleotide the Dewar is exclusively formed from an excited valence state, but not in the free base 5-methyl-2-pyrimidinone (5M2P) nor with a sliced backbone. The mechanism is elucidated by the analysis of conical intersections which show, that the photochemical deactivation of T(6-4)T is strongly in influenced by the confinement in the dinucleotide, leading to T(Dewar)T formation, whereas in 5M2P the photophysical protection is ensured by a conical intersection seam. The implementation of the ONIOM-method into the non-adiabatic mixed quantum classical dynamics allows to follow the formation of the T(Dewar)T lesion as well as the competing photophysical relaxation. C=O-vibrations are identied as unambiguous spectroscopic probe of the 4π-sigmatropic rearrangement for highly sensitive UV/VIS pump - IR probe experiments which were successful in following the reaction in real time. As a second photoreaction the ultrafast phototriggered reaction of benzhydryl cations with methanol is investigated. The mechanism of the laser induced generation of highly reactive benzhydryl cations from the precursor molecule diphenylmethyl chloride is derived by quantum chemical and quantum dynamical methods. For the competing reaction channels of ion pair and radical pair formation the interaction of different electronic states leads to ultrafast bond cleavage. The homolytic bond cleavage as a parallel reaction-channel is already accessible in the FC region by the participation of lone-pairs of the Cl-leaving group. Based on ab initio data a system Hamiltonian is derived which is suitable to describe the multidimensional dissociation process in a reduced reactive coordinate space. Quantum dynamical calculations show that bond cleavage induced by a Fourier limited femtosecond laser pulse provides the ion pair despite its higher potential energy and the existence of conical intersections. The subsequent bimolecular bond formation, which constitutes the second part of the SN1 reaction, is investigated by on-the-fly molecular dynamics simulations in a micro-solvation approach. The calculated solvation correlation function and time resolved UV/VIS spectra are compared to recent experimental findings. By the detailed microscopic description the assignment of the spectral features to different molecular events is possible. The results show that the rising spectral signature of the generated benzhydryl cations is not directly correlated with the bond cleavage, a fact that has to be considered in the interpretation of the signal for a complete understanding of the reaction mechanism

Noncovalent Interactions Of Hydrated Dna And Rna Mapped By 2d-ir Spectroscopy

Biomolecules couple to their aqueous environment through a variety of noncovalent interactions. Local hydration structures at the surface of DNA and RNA are frequently determined by directed hydrogen bonds with water molecules, complemented by non-specific electrostatic and many-body interactions. I will present recent results from 2D-IR spectroscopy of sugar-phosphate backbone vibrations of native and artificial DNA and RNA, together with theoretical calculations of molecular couplings and molecular dynamics simulations. The results reveal the femtosecond fluctuation dynamics of the water shell, a short-range character of Coulomb interactions, and the strength and fluctuation amplitudes of interfacial electric fields [1,2]. Recent applications of phosphate vibrations [3,4,5] as probes for local hydration patterns and contact ion pair configurations hold strong potential for quantifying folding-induced changes of the ion distribution around DNA and RNA on a multitude of time scales. \vspace{0.5cm} References: 1. T. Siebert, B. Guchhait, Y. Liu, B. P. Fingerhut, T. Elsaesser, J. Phys. Chem. Lett. 7, 3131 (2016). 2. E. M. Bruening, J. Schauss, T. Siebert, B. P. Fingerhut, T. Elsaesser, J. Phys. Chem. Lett. 9, 583 (2018). 3. J. Schauss, F. Dahms, B. P. Fingerhut, T. Elsaesser, J. Phys. Chem. Lett. 10, 238 (2019). 4. A. Kundu, J. Schauss, B. P. Fingerhut, T. Elsaesser, J. Phys. Chem. B, 124, 2132 (2020). 5. J. Schauss, A. Kundu, B. P. Fingerhut, T. Elsaesser, J. Phys. Chem. B, 125, 740 (2021)

Algorithms for Designing Nonblockings Communication Networks with General Topologies

A framework is given for specifying nonblocking traffic requirements in a connection-oriented communications network. In this framework, connections may be form one point to one other point, or they may involve multiple points. Different connections may have different data rates. The communication networks are constructed from switches (or nodes) and trunks, which connect pairs of switches. This framework is intended to model Asynchronous Transfer Mode (ATM) networks and traffic. Several computational problems are formulated, each intended to find a minimum cost configuration of switches and trunks which satisfy given traffic requirements. Efficient algorithms have been found for some problems, and computational hardness results for others

Stereotype threat among black and white women in health care settings

The first of its kind, the present experiment applied stereotype threat-the threat of being judged by or confirming negative group-based stereotypes-to the health sciences. Black and White women (N = 162) engaged in a virtual health care situation. In the experimental condition, one\u27s ethnic identity and negative stereotypes of Black women specifically were made salient. As predicted, Black women in the stereotype threat condition who were strongly identified as Black (in terms of having explored what their ethnic identity means to them and the role it plays in their lives) reported significantly greater anxiety while waiting to see the doctor in the virtual health care setting than all other women. It is hypothesized that stereotype threat experienced in health care settings is one overlooked social barrier contributing to disparities in health care utilization and broader health disparities among Black women