VictorJuiz/thesis huggingface dataset:
Contributions of COMT and DAT to regulation of phasic dopamine release and reward-guided behaviour
Keywords: Dopamine transporter
Nucleus accumbens
Reinforcement Learning
Decision making
Motivation
Catechol-O-methyltransferase
Dopamine
Prefrontal cortex

Fine temporal regulation of dopamine transmission is critical to its effects on behaviour. Dopamine can be cleared from the synapse either by recycling via the dopamine transporter (DAT) or by enzymatic degradation involving catechol-O-methyltransferase (COMT). DAT recycling predominates in striatum and contributes to dopaminergic regulation of reward-guided behaviour, while COMT degradation predominates in cortex and modulates executive functions. However, human functional imaging studies demonstrate interactive effects of DAT and COMT genotype, suggesting that the traditional division between DAT and COMT is not so clear-cut. Given the interdependence of mesolimbic and mesocortical circuitry and the presence of COMT in the striatum, it is possible that DAT and COMT interact to a greater extent than previously thought.
We investigated the contributions of DAT and COMT to regulation of dopamine transmission and reward-guided behaviour by combining in vivo electrochemical recording, pharmacology, and behavioural testing in mice. Using fast scan cyclic voltammetry to record evoked dopamine release in anaesthetised animals, we found that systemic DAT blockade increased the size of dopamine transients in the nucleus accumbens (NAc) but not in the medial frontal cortex (MFC), demonstrating that DAT regulates phasic striatal dopamine release and confirming that DAT makes little contribution to regulation of cortical dopamine transmission. Unexpectedly, COMT inhibition did not affect evoked dopamine transients in either the NAc or the MFC. In agreement with these findings, systemic administration of a DAT blocker, but not of a COMT inhibitor, increased motivation to work for reward in a progressive ratio paradigm. COMT inhibition also had little effect on reinforcement learning (RL) strategies during reward-guided decision making. Intriguingly, however, we found that DAT blockade both decreased the influence of model-free RL and increased the influence of model-based RL on behaviour.
Our study confirms that DAT regulates dopamine transmission in striatum but not in cortex and indicates that sub-second changes in dopamine transmission in both regions are largely insensitive to COMT. However, our behavioural data reveal the importance of striatal dopamine in multiple components of reward-guided behaviour, including both motivational aspects traditionally associated with striatum as well as cognitive aspects heretofore mainly associated with cortical function. Together, these findings emphasise that reward processing occurs across corticostriatal circuits and contribute to our understanding of how striatal dopamine transmission regulates reward-guided behaviours.
Network structure, brokerage, and framing: how the internet and social media facilitate high-risk collective action
Keywords: brokerage
political protests
collective action
social media
internet
Russia
social networks
framing

This thesis investigates the role of network structure, brokerage, and framing in high-risk collective action. I use the protest movement that emerged in Russia following falsified national elections in 2011 and 2012 as an empirical case study. I draw on a unique dataset of nearly 30,000 online documents and the linking structure of over 3,500 Russian Web sites. I employ a range of computational social science methods, including Exponential Random Graph Modeling, an advanced statistical model for social networks, social network analysis, machine learning, and latent semantic analysis.
I address three research questions in this thesis. The first asks if a protest network challenging a hybrid regime will have a polycentric or hierarchical structure, and if that structure changes over time. Polycentric networks are conducive to high-risk collective action and are robust to the targeted removal of key nodes, while hierarchical networks can more easily mobilize protesters and spread information. I find that the Russian protest network has a polycentric structure only at the beginning of the protests, and moves towards a less effective hierarchical structure as the movement loses popular support. The second research question seeks to understand if brokered text is actually novel, and if that text is more novel in polycentric networks than in hierarchical ones. Brokers are the individuals or nodes in a network that connect disparate groups through weak ties and close structural holes. Brokers are advantageous because they have access to and spread novel information. I find that the text among nodes in brokered relationships is indeed novel, but that information novelty decreases when networks have a hierarchical structure. The last research question asks if a protest movement in a high-risk political setting can be more successful than the government at spreading its preferred frames, and within such a movement, whether moderate or extremist framing is more prevalent. I find that the opposition is far more effective than the government in spreading its frames, even when the government organizes massive counter protests. Within the movement, moderates are more likely to have their framing adopted online than extremists, unless violence occurs at protests.
The findings suggest that movements should build flatter, more diffuse networks by ensuring that brokers tie together diverse protest constituencies. The findings also provide evidence against those who claim that authoritarian governments are more effective in shaping online discourse than oppositional movements, and also suggest that movements should advance moderate framing in order to attract a wider base of support among the general population.
J. S. Bach at the coffee house: music as edifying practice
Keywords: Performance History
Collegium Musicum
coffee-house culture
Music Analysis
JS Bach
18th-Century Leipzig

This thesis proposes a new critical perspective on Bach's Collegium musicum and its performances at a Leipzig coffee house. Based on a range of fresh literary, architectural, and administrative sources, I argue that coffee houses in Bach’s time were highly prestigious, if often controversial performance-venues. As a cultural sphere, they were guided by a neo-humanist ideal, known as 'useful edification' (nützliche Erbauung), which has not been recognised by scholars so far. Yet, applied to musical practice, the notion of useful coffee-house edification can provide a fruitful paradigm for rethinking the reception of Bach's music in its secular performance-contexts. As the contents of several coffee-house periodicals from the early eighteenth century suggest, edifying thought (also described as pondering, or Nachsinnen) was widely understood as a combination of critical and associative thought, which closely resembled Bach's own preoccupation with exploring musical ideas as rhetorical inventiones. Seen this way, a rich reception context emerges that, as a historical web of anthropological meaning, can shed new light, for example, on the socio-cultural context of Bach's keyboard music that was published under the title of Clavier-Übung. In addition, it can reveal how Bach's musical inventions were often combined with further allegorical signs to result in rich music-dramatic, and arguably also emblematic tableaux in a range of secular cantatas. A newly-recovered document relating to Bach's cantata Blast Lermen ihr Feinde (BWV 205a) suggests, for example, that the dramma per musica was performed as part of a highly theatrical event that staged an emblematic representation of the coronation of August III as Polish King in 1734. But recognising Bach’s reliance on emblematic allegories can also yield new perspectives on, for example, Hercules at the Crossroads (BWV 213) and The Contest between Phoebus and Pan (BWV 201). Viewed as 'useful' and 'edifying' performances, I argue that their music-dramatic symbolism articulated a rich counterpoint of religious, secular and political meanings that can be linked to a corresponding variety of pragmatic, artistic and satirical agendas. .
Early perspectives on works of the law: a patristic study
Keywords: Justification
Patristics
Works of the law
New Perspective on Paul
Old Perspective on Paul

In Paul's epistles to the Romans and the Galatians, the Apostle famously opposes "works of the law" within disputes regarding Jews and the law. But what are these works, what do they signify, and why are they rejected? Such questions are widely contested in New Testament scholarship, with responses constituting an important fault line in contemporary debates between "old" and "new" perspectives on Paul. This study engages these debates by investigating the views of the earliest patristic sources on this issue, which carry distinct heuristic value due to their historical, cultural, and personal proximity to Paul. Part I of this thesis presents the theoretical basis for using early reception within a period of "living memory" to engage contested areas of interpretation. Part II outlines the "old" and "new" perspectives on works of the law, with Luther, Calvin, Bultmann and Moo presented for the "old" perspective, and the "new" represented by Sanders, Dunn and Wright. Part III presents a comprehensive investigation of early patristic writings, stretching from the Didache to Irenaeus, which evaluates each source's usage of the relevant Pauline texts and their understanding of the meaning, significance, and reasons for opposing works of the law. Part IV concludes with a synthesis of these early views, an assessment of how they relate to the "old" and "new" perspectives, and implications for what their testimony suggests about Paul's meaning in the biblical texts. While neither perspective aligns uniformly with the patristic sources, it is concluded that contrary to current nomenclature, the "new" perspective finds greater correspondence with Christian antiquity than the "old" on this issue, and given these sources’ proximity to Paul and the consistent and uncontroversial nature of their interpretations, the burden of proof in contemporary debates should be carried by those who would run counter to these early perspectives.
Investigation of interface behaviour on perovskite solar cells
Keywords: interface science
perovskite solar cells
condensed matter physcis

Historically, the interfaces and charge transportation layers dictate the performance in heterojunction solar cells. This thesis addresses the interface behaviours and the interfacial layers within perovskite solar cells (PSCs), and provides insights and practicable solutions to facilitate the realisation of efficient PSCs.
To achieve efficient charge collection with interlayer fabricated with low-temperature processes, a graphene-TiO2 nanocomposite is demonstrated; By investigating the carrier transport, we found the insertion of graphene improved the electron collection efficiency with its high surface area and ballistic carrier conduction properties, and in conjunction with pre-synthesised TiO2, we have successfully circumvented the need for high-temperature annealing, enabling the whole device to be fabricated at under 150 °C.
While the anomalous hysteresis behaviour which is widely observed in regular PSCs structure is a significant problem, the quest of stable PSCs seems to be answered by the use of inverted PSCs structures. We show a detailed development of inverted PSCs which are deconstructed layer by layer. Numerous approaches have been tailored to improve interfaces, and energy levels between layers, leading to an efficient and hysteresis-free perovskite solar cells.
Lastly, an in-depth study of impurity doping is investigated using Al3+. The doping with small metal ions in the perovskite precursor has been found to influenced the crystallisation and optoelectronic properties of the perovskite crystals. Here, for the first time, the correlation between reduced structural crystal defects is clearly linked to enhanced photovoltaic properties, with the best performance for the lowest electronic disorder in the CH3NH3PbI3 crystal.
Towards quantitative intra-nuclear dose mapping of auger emitting radionuclides used for targeted radiotherapy
Keywords: autoradiography
AFM
photoresist
Auger electron-emitters

Targeted radiotherapy (TRT) is a technique which allows for individual cancer cells to be targeted by radiation. However, there is variation in uptake at the whole body, organ, cellular and subcellular levels. This distribution affects the biological efficacy of the TRT agents. To address this problem, novel techniques have been developed and demonstrated. These aim to provide quantitative information about the spatial distribution of Auger electron (AE) emitting radiopharmaceuticals at the subcellular level.
Two methods have been developed. The first, photoresist autoradiography (PAR), uses photoresists as an autoradiography substrate, and the second uses microautoradiography (MAR) and a transmission electron microscope (TEM). The techniques have been demonstrated using the AE emitter indium-111.
Firstly, PAR is demonstrated using poly (methyl methacrylate) (PMMA). Photoresists were exposed to indium-111 which had been internalised into cells, and the photoresists were analysed using atomic force microscopy (AFM). The technique has a theoretical resolution in the nanometre range and was able to demonstrate cellular patterns on the micron scale. To gain quantitative information, the photoresist response (depth of pattern) was calibrated as a function of electron fluence and a model of the patterns was created. Combining the calibration data with the point source model allowed the position and intensity of the internalised source terms to be estimated using the PAR method.
Secondly, a technique for electron microscope-microautoradiography (EM-MAR) was developed. The processing conditions of the MAR technique were determined and staining techniques developed, to produce high quality TEM micrographs. A time course experiment showed the distribution and variation in the uptake of the radiopharmaceutical at the cellular level.
Both techniques are able to provide information about the subcellular distribution of the radioactivity at a higher resolution than current techniques. Both enable the collection of information which can be used in microdosimetric calculations.
Structural and functional studies of the transcriptional regulator Seb1 in fission yeast
Keywords: CTD-interacting domain

RNA polymerase II (Pol II) is responsible for the transcription of all protein-coding and some non-coding genes in eukaryotes. Its largest subunit, Rpb1, contains a unique C-terminal domain (CTD) which consists of repeats of the heptad YSPTSPS. It acts as a binding platform for proteins that control the different stages of transcription and their recruitment is regulated mainly by differential phosphorylation of residues contained within the CTD. Previous studies could unveil proteins containing a CTD-interacting domain (CID) as important players that specifically bind to certain phosphorylation types of the CTD. More precisely, they were shown to be important for the last step of transcription, termination. Despite extensive research over the past 30 years, the exact mechanism of how these proteins facilitate the dislodgement of Pol II from the DNA template, still remains unknown. The work presented here contains detailed studies of the CID-containing protein Seb1 from the fission yeast Schizosaccharomyces pombe, revealing an unexpectedly broad role of this protein in transcription termination.
In addition to a CID, Seb1 also contains an RNA recognition motif (RRM) which allows direct binding to RNA. Here, I present high-resolution crystal structures of both domains of Seb1. While the CID has a very conserved fold, the RNA binding regions contains an unusual arrangement of a canonical RRM intertwined with a second domain that are both important for RNA binding. Structure-based mutations were introduced and a combination of in vitro and genome-wide in vivo studies uncover Seb1 as an essential player in transcription termination. Importantly, both domains are required to promote the full function of Seb1. Despite its homology to the well-studied budding yeast protein Nrd1, the role of Seb1 in fission yeast is quite different. This thesis therefore provides important insight into the mechanisms that underlie eukaryotic transcription termination.
A comparative study of reliance in the unilateral breaking-off of contractual negotiations
Keywords: comparative law
negotiations
reliance

This thesis explores the theoretical basis of precontractual liability for the unilateral breaking-off of negotiations, by undertaking a comparative study between three selected jurisdictions (Germany, France and Chile). It defines a 'paradigm case' and focuses on it in order to find the theoretical basis of this liability. Traditionally, precontractual liability for breaking off negotiations has been founded upon or at least linked with the notion of good faith. This thesis, however, argues that in the selected jurisdictions the true basis of this liability is the notion of 'reliance' and distinguishes two dimensions of reliance (referring to them as 'trust-based' and 'expectation-based'). It analyses the relationship between these dimensions arguing that in the selected jurisdictions the trust-dimension merges with the general principle of good faith and that the expectation-dimension emanates from the trust-dimension. This thesis argues that this innovative approach to the theoretical analysis of the foundation of this liability could have important practical consequences in jurisdictions which do not embrace a general principle of good faith. It focuses on English law, as a contrasting jurisdiction to the selected jurisdictions, in that it rejects a general principle of good faith and, especially, the notion of a duty to negotiate in good faith, which is generally considered to lead necessarily to the rejection of a general principle of precontractual liability. This thesis demonstrates that while English law can provide protection for certain cases of precontractual liability, it currently does not protect the paradigm case. It argues that if the analysis is shifted from good faith to the notion of reliance, English law could develop one or more of its particular solutions in order to protect the paradigm case, if it desired to do so, and explores how such a development could be implemented without establishing a general principle of precontractual liability.
Electronic delocalisation in linear and cyclic porphyrin oligomers
Keywords: torsion
nanoring
density functional theory
dft
aromaticity
porphyrin
coherence
ring current
butadiyne
physical organic
nmr
quantum interference
antiaromaticity

This thesis presents a combined experimental and computational evaluation of the physical-organic properties of butadiyne-linked porphyrin oligomers. The principal result from the thesis is the synthesis and characterisation of the largest aromatic and antiaromatic systems to date, in the form of an oxidised [6]-porphyrin nanoring, with diameter 2.4 nm. This large electronically coherent system provides insight into the connection between aromatic ring currents and persistent currents in metal and semiconductor mesoscopic rings.
Chapter 1 briefly reviews the concepts used in the remainder of the thesis, with a particular focus on aromaticity.
In Chapter 2, the barrier to inter-porphyrin torsional rotation in a butadiyne-linked porphyrin dimer is determined computationally and experimentally to be 3 kJ mol−1. The barrier height is closely related to the resonance delocalisation energy between the porphyrin subunits.
In Chapter 3 we show that by oxidising a butadiyne-linked [6]-porphyrin nanoring to its 4+ and 6+ oxidation states, the nanoring becomes antiaromatic and aromatic respectively. In contrast, the neutral oxidation state exhibits only local aromaticity for the six porphyrin units. The 12+ cation can also be generated, and exhibits local antiaromaticity for each porphyrin unit. The characterisation of (anti)aromaticity employs NMR and computational techniques.
In Chapter 4, the properties of cation radicals of linear and cyclic porphyrin oligomers are explored. Cations generated by spectroelectrochemistry are measured by optical spectroscopies, and chemically generated radical monocations are examined by cw/pulsed EPR spectroscopies. EPR and optical spectroscopies agree that the dimer monocation radical is fully delocalised, in Robin-Day Class III, whereas the monocations of longer oligomers are localised over 2–3 porphyrin units (Class II).
In Chapter 5, photophysical and computational investigations into excited state aromaticity in porphyrin nanorings are presented. The computational results suggest the presence of aromaticity in the triplet excited states, but experiment fails to convincingly demonstrate the effect.
Computational results in Chapter 6 show that a butadiyne linked [6]-porphyrin nanoring in which one butadiyne (C&#
Complexity in Rhodobacter sphaeroides chemotaxis
Keywords: PALM
rhodobacter sphaeroides
bacterial two-hybrid
free swimming
bacterial chemotaxis
complex chemotaxis
BACTH
chemotaxis
tethered cell

Perceiving and responding to the environment is key to survival. Using the prokaryotic equivalent of a nervous system – the chemotaxis system – bacteria sense chemical stimuli and respond by adjusting their movement accordingly.
In chemotactic bacteria, such as the well-studied E. coli, environmental nutrient sensing is achieved through a membrane embedded protein array that specifically clusters at the cell poles. Signalling to the motor is performed by activation of the CheA kinase, which phosphorylates CheY and CheB. CheY–P tunes the activity of the flagellar motor while CheB–P, together with CheR is involved in adaptation to the stimulus. In E. coli, a dedicated phosphatase terminates the signal.
Most bacterial species however, have a much more complex chemotaxis network. Rhodobacter sphaeroides, a model organism for complex chemotaxis systems, has one membrane-embedded chemosensory array and one cytoplasmic chemosensory array, plus several homologs of the E. coli chemotaxis proteins. Signals from both arrays are integrated to control the rotation of a single start-stop flagellar motor.
The phosphorelay network has been studied extensively through in vitro phosphotransfer while in vivo studies have established the components of each array and the requirements for formation. Mathematical modelling has also contributed towards inferring connectivities within the signalling network.
Starting by constructing a two-hybrid-based interaction network focused on the components of the cytoplasmic chemosensory array, this thesis further addresses its associated adaptation network through a series of in vivo techniques.
The swimming behaviour of series of deletion mutants involving the adaptation network of R. sphaeroides is characterised under steady state conditions as well as upon chemotactic stimulation. New connectivities within the R. sphaeroides chemotaxis network are inferred from analysing these data together with results from in vivo photoactivation localisation microscopy of CheB2.
The experimental results are used to propose a new model for chemotaxis in R. sphaeroides.