Psychoanalysis and the law beyond the Oedipus : a study in legal fictions.

PhDThe present thesis considers the function of law in the political from the perspective of psychoanalysis, a discipline which foregrounds the subject. Drawing from the Lacanian contributions to psychoanalytic theory, I begin by assessing the validity of the Oedipal hypothesis for the purposes of understanding the dynamics of collective life. My analysis of civilisation in psychoanalytic terms will expose the subject as the seat of 'certain key phenomena which, despite their deeply intimate character, play themselves out in the field of law, in the confines of the institution, or again in the political realm: essentially, culpability, belief and love. I will argue that, although these phenomena irretrievably obstruct the rational unfolding of discourse, they also impel the precipitation of the subject's attachment to the political, and permit the consolidation thereof through the medium of transference. Yet, and in contradistinction to other strands of psychoanalytic jurisprudence, in this work psychoanalysis will be used neither as an hermeneutic tool nor as an analogical model. Indeed, my purpose is to evidence the existence of a certain continuity between the unconscious as discourse and the political order. This continuity between the unconscious and the political will be presented in terms of the logic of exception, which structures the subject's relation to language, and which Lacan identified as the structural core of the Oedipus complex. I will then apply Lacan's hypothesis of the exceptional structure of discourse to the theories of three political thinkers, chosen for the distinctness of their approach: Legendre, Bentham and Foucault. Finally, I will argue for the dispensability of the function of the Ideal, parasitic occupier of what should remain the structurally `empty' place of exception

CA 15.3 measurements for separating FDG PET/CT positive from negative findings in breast carcinoma recurrence

In breast cancer CA 15.3 is considered the tumour marker of choice. CA 15.3 is directly related to the disease extent and to hormone status (estrogen receptor ER+/ ER-, progesterone receptor PR+/PR-). This study was designed to assess the impact of disease extent, hormone receptor and HER2-status, and circulating blood volume on the area-under the ROC-curve of CA 15.3 to separate FDG PET positive from negative findings. Patients, methods: We retrospectively evaluated 379 FDG PET/CT examinations performed in 80 patients with breast cancer. Blood volumes were derived using the formulas by Nadler and multiplied by their corresponding CA 15.3 measurement. Results: ROC-curve analysis revealed an AUC of 0.695 (p = 0.0001) for CA 15.3 to separate FDG PET positive from negative findings. AUC measurements to separate normal scan findings from loco-regional disease and metastatic disease were 0.527 (p = 0.587) and 0.732 (p = 0.0001), respectively. AUC measurements for CA 15.3 to separate positive from negative FDG PET findings, in ER+ and ER-patients, were respectively 0.772 (p = 0.0001) and 0.596 (p = 0.143). AUC measurements for CA 15.3 to separate positive from negative FDG PET findings, in PR+ and PR-patients, were respectively 0.675 (p = 0.0001) and 0.694 (p = 0.0001). In HER2-positive and -negative patients, the AUC measurements were respectively 0.594 (p = 0.178) and 0.701 (p = 0.0001) to separate positive from negative FDG PET findings. Conclusion: The AUC for CA 15.3 measurements to separate FDG PET positive from negative findings in breast cancer patients with suspected recurrence proved to be directly related to the extent of the recurrent disease and hormone receptor status and inversely related to HER2-status. Correcting CA 15.3 measurements for blood volumes did not impact the AUC

Efficient construction of free energy profiles of breathing metal–organic frameworks using advanced molecular dynamics simulations

In order to reliably predict and understand the breathing behavior of highly flexible metal–organic frameworks from thermodynamic considerations, an accurate estimation of the free energy difference between their different metastable states is a prerequisite. Herein, a variety of free energy estimation methods are thoroughly tested for their ability to construct the free energy profile as a function of the unit cell volume of MIL-53(Al). The methods comprise free energy perturbation, thermodynamic integration, umbrella sampling, metadynamics, and variationally enhanced sampling. A series of molecular dynamics simulations have been performed in the frame of each of the five methods to describe structural transformations in flexible materials with the volume as the collective variable, which offers a unique opportunity to assess their computational efficiency. Subsequently, the most efficient method, umbrella sampling, is used to construct an accurate free energy profile at different temperatures for MIL-53(Al) from first principles at the PBE+D3(BJ) level of theory. This study yields insight into the importance of the different aspects such as entropy contributions and anharmonic contributions on the resulting free energy profile. As such, this thorough study provides unparalleled insight in the thermodynamics of the large structural deformations of flexible materials

A theoretical and experimental spectroscopy study on methanol and ethanol conversion over H-SAPO-34

The elucidation of the structure-activity relation of zeolites or zeotype materials remains very challenging. Recent advances in both theoretical and experimental techniques provide new opportunities to study these complex materials and any catalytic reaction occurring inside. In order to establish new active reaction routes, the knowledge of formed intermediates is crucial. The characterization of such intermediates can be done using a variety of spectroscopic techniques. In this contribution, methanol and ethanol conversion over H-SAPO-34 is investigated using IR and UV-VIS measurements. Calculated adsorption enthalpies of methanol and ethanol in a large SAPO 44T finite cluster show the stronger adsorption of the larger alcohol by 14 kJ mol-1. Dispersion contributions are found to be crucial. IR spectra are calculated for the clusters containing the adsorbed alcohols and matched with experimental data. In addition, the cluster is also loaded with singly methylated cationic hydrocarbons as these are representative reaction intermediates. A detailed normal mode analysis is performed, enabling to separate the framework-guest contributions. Based on the computed data in situ DRIFT experimental peaks could be assigned. Finally, contemporary DFT functionals such as CAM-B3LYP seem promising to compute gas phase UV-VIS spectra

Minimal Basis Iterative Stockholder: Atoms in Molecules for Force-Field Development

Atomic partial charges appear in the Coulomb term of many force-field models and can be derived from electronic structure calculations with a myriad of atoms-in-molecules (AIM) methods. More advanced models have also been proposed, using the distributed nature of the electron cloud and atomic multipoles. In this work, an electrostatic force field is defined through a concise approximation of the electron density, for which the Coulomb interaction is trivially evaluated. This approximate "pro-density" is expanded in a minimal basis of atom-centered s-type Slater density functions, whose parameters are optimized by minimizing the Kullback-Leibler divergence of the pro-density from a reference electron density, e.g. obtained from an electronic structure calculation. The proposed method, Minimal Basis Iterative Stockholder (MBIS), is a variant of the Hirshfeld AIM method but it can also be used as a density-fitting technique. An iterative algorithm to refine the pro-density is easily implemented with a linear-scaling computational cost, enabling applications to supramolecular systems. The benefits of the MBIS method are demonstrated with systematic applications to molecular databases and extended models of condensed phases. A comparison to 14 other AIM methods shows its effectiveness when modeling electrostatic interactions. MBIS is also suitable for rescaling atomic polarizabilities in the Tkatchenko-Sheffler scheme for dispersion interactions.Comment: 61 pages, 12 figures, 2 table

Hydroponic isotope labeling of entire plants (HILEP) for quantitative plant proteomics

Quantitative analysis by mass spectrometry (MS) is a major challenge in proteomics as the correlation between analyte concentration and signal intensity is often poor due to varying ionisation efficiencies in the presence of molecular competitors. However, relative quantitation methods that utilise differential stable isotope labelling and mass spectrometric detection are available. Many drawbacks inherent to chemical labelling methods (ICAT, iTRAQ) can be overcome by metabolic labelling with amino acids containing stable isotopes (e.g. 13C and/or 15N) in methods such as Stable Isotope Labelling with Amino acids in Cell culture (SILAC). SILAC has also been used for labelling of proteins in plant cell cultures (1) but is not suitable for whole plant labelling. Plants are usually autotrophic (fixing carbon from atmospheric CO2) and, thus, labelling with carbon isotopes becomes impractical. In addition, SILAC is expensive. Recently, Arabidopsis cell cultures were labelled with 15N in a medium containing nitrate as sole nitrogen source. This was shown to be suitable for quantifying proteins and nitrogen-containing metabolites from this cell culture (2,3). Labelling whole plants, however, offers the advantage of studying quantitatively the response to stimulation or disease of a whole multicellular organism or multi-organism systems at the molecular level. Furthermore, plant metabolism enables the use of inexpensive labelling media without introducing additional stress to the organism. And finally, hydroponics is ideal to undertake metabolic labelling under extremely well-controlled conditions. We demonstrate the suitability of metabolic 15N hydroponic isotope labelling of entire plants (HILEP) for relative quantitative proteomic analysis by mass spectrometry. To evaluate this methodology, Arabidopsis plants were grown hydroponically in 14N and 15N media and subjected to oxidative stress

Integrated functions among multiple starch synthases determine both amylopectin chain length and branch linkage location in Arabidopsis leaf starch

This study assessed the impact on starch metabolism in Arabidopsis leaves of simultaneously eliminating multiple soluble starch synthases (SS) from among SS1, SS2, and SS3. Double mutant ss1- ss2- or ss1- ss3- lines were generated using confirmed null mutations. These were compared to the wild type, each single mutant, and ss1- ss2- ss3- triple mutant lines grown in standardized environments. Double mutant plants developed similarly to the wild type, although they accumulated less leaf starch in both short-day and long-day diurnal cycles. Despite the reduced levels in the double mutants, lines containing only SS2 and SS4, or SS3 and SS4, are able to produce substantial amounts of starch granules. In both double mutants the residual starch was structurally modified including higher ratios of amylose:amylopectin, altered glucan chain length distribution within amylopectin, abnormal granule morphology, and altered placement of α(1→6) branch linkages relative to the reducing end of each linear chain. The data demonstrate that SS activity affects not only chain elongation but also the net result of branch placement accomplished by the balanced activities of starch branching enzymes and starch debranching enzymes. SS3 was shown partially to overlap in function with SS1 for the generation of short glucan chains within amylopectin. Compensatory functions that, in some instances, allow continued residual starch production in the absence of specific SS classes were identified, probaby accomplished by the granule bound starch synthase GBSS1.ANR Génoplante GPLA0611GEuropean Union-FEDER, Région Nord Pas de Calais ARCir PlantTEQ5National Science Foundation DBI-0209789Comisión Interministerial de Ciencia y Tecnología BIO2009-07040Junta de Andalucía P09-CVI-470

A role for human N-alpha acetyltransferase 30 (Naa30) in maintaining mitochondrial integrity

N-terminal acetylation (Nt-acetylation) by N-terminal acetyltransferases (NATs) is one of the most common protein modifications in eukaryotes. The NatC complex represents one of three major NATs of which the substrate profile remains largely unexplored. Here, we defined the in vivo human NatC Nt-acetylome on a proteome-wide scale by combining knockdown of its catalytic subunit Naa30 with positional proteomics. We identified 46 human NatC substrates, expanding our current knowledge on the substrate repertoire of NatC which now includes proteins harboring Met-Leu, Met-Ile, Met-Phe, Met-Trp, Met-Val, Met-Met, Met-His and Met-Lys N termini. Upon Naa30 depletion the expression levels of several organellar proteins were found reduced, in particular mitochondrial proteins, some of which were found to be NatC substrates. Interestingly, knockdown of Naa30 induced the loss of mitochondrial membrane potential and fragmentation of mitochondria. In conclusion, NatC N-tacetylates a large variety of proteins and is essential for mitochondrial integrity and function

⁹⁹ᵐTc SPECT imaging agent based on cFLFLFK for the detection of FPR1 in inflammation

Non-invasive imaging of the inflammatory process can provide a great deal of insight into a wide variety of diseases states, aiding diagnosis, evaluation and effective targeted treatment. During inflammation, blood borne leukocytes are recruited, through a series of activation and adhesion steps, to the site of injury or infection where they migrate across the blood vessel wall into the tissue. Thus, tracking leukocyte recruitment and accumulation provides a dynamic and localised read out of inflammatory events. Current leukocyte imaging techniques require ex vivo labelling of patient blood, involving laborious processing and potential risks to both patient and laboratory staff. Utilising high affinity ligands for leukocyte specific receptors may allow for injectable tracers that label leukocytes in situ, omitting potentially hazardous ex vivo handling. Formyl peptide receptors (FPRs) are a group of G-protein coupled receptors involved in the chemotaxis and inflammatory functioning of leukocytes. Highly expressed on leukocytes, and up regulated during inflammation, these receptors provide a potential target for imaging inflammatory events. Herein we present the synthesis and initial in vitro testing of a potential Single Photon Emission Computed Tomography (SPECT) leukocyte tracer. The FPR1 antagonist cFLFLFK-NH₂, which displays high affinity with little physiological effect, has been linked via a PEG motif to a ⁹⁹ᵐTc chelate. This tracer shows in vitro binding to human embryonic kidney cells expressing the FPR1 receptor, and functional in vitro tests reveal cFLFLFK-NH₂ compounds to have no effect on inflammatory cell functioning. Overall, these data show that ⁹⁹ᵐTc.cFLFLFK-NH₂ may be a useful tool for non-invasive imaging of leukocyte accumulation in inflammatory disease states