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The effect of personality and gender on individuals' propensity for corruption and corrupt behavior
(2020)
Personalisierte A-Konstanten-Optimierung zur intraokularen Berechnung einer AcrySof SA60AT der Firma Alcon. Bei Kataraktoperationen werden künstliche Linsen implantiert. Die postoperative Brechkraft des Systems Brille-Auge wird mit verschiedenen IOL-Formeln berechnet. Jede Formel enthält eine A-Konstante, welche die Intraokularlinse repräsentiert. In dieser Arbeit geht es darum, die A-Konstante einer AcrySof SA60AT speziell auf den Operateur im Augenzentrum Maus zu optimieren. Dadurch erreicht man eine personalisierte Optimierung, die eine deutliche Verbesserung der postoperativen Refraktionsergebnisse bedeutet. Dies steht im Vergleich zur ULIB (User Group for Laser Interference Biometrie), die sich auch die Optimierung von A-Konstanten zur Aufgabe gemacht hat, jedoch allgemeine, optimierte Konstanten für alle Anwender der Gruppe anbietet. Diese allgemeinen Konstanten sind deutlich besser als die vom Hersteller angegeben, spiegeln jedoch nicht die individuellen Operationsmethoden wieder. In dieser Arbeit wird gezeigt, dass personalisierte, auf den Operateur abgestimmte, Konstanten die postoperativen Ergebnisse noch weiter verbessern. In dieser Studie wurde die A-Konstante bei 50 Patientenaugen optimiert und die Ergebnisse ohne und mit Optimierung ausgewertet. Verschieden lange Augen wurden selektiert, um festzustellen, bei welchen Augen die Optimierung den größten Vorteil bringt. Im Folgenden werden die Methode und die Ergebnisse dieser Untersuchung genauer dargestellt.
Tóth, Gergely ; Neumann, Thomas ; Berthet, Amandine ; Masliah, Eliezer ; Spencer, Brian ; Tao, Jiahui ; Jobling, Michael ; Gardai, Shyra ; Bertoncini, Carlos ; Cremades, Nunilo ; Bova, Michael ; Ballaron, Stephen ; Chen, Xiao-Hua ; Mao, Wenxian ; Nguyen, Phuong ; Tabios, Mariano ; Tambe, Mitali ; Rochet, Jean-Christophe ; Junker, Hans-Dieter ; Schwizer, Daniel ; Sekul, Renate ; Ott, Inge ; Anderson, John ; Szoke, Balazs ; Hoffman, Wherly ; Christodoulou, John ; Yednock, Ted ; Agard, David ; Schenk, Dale ; McConlogue, Lisa
The over-expression and aggregation of α-synuclein (αSyn) are linked to the onset and pathology of Parkinson's disease. Native monomeric αSyn exists in an intrinsically disordered ensemble of interconverting conformations, which has made its therapeutic targeting by small molecules highly challenging. Nonetheless, here we successfully target the monomeric structural ensemble of αSyn and thereby identify novel drug-like small molecules that impact multiple pathogenic processes. Using a surface plasmon resonance high-throughput screen, in which monomeric αSyn is incubated with microchips arrayed with tethered compounds, we identified novel αSyn interacting drug-like compounds. Because these small molecules could impact a variety of αSyn forms present in the ensemble, we tested representative hits for impact on multiple αSyn malfunctions in vitro and in cells including aggregation and perturbation of vesicular dynamics. We thereby identified a compound that inhibits αSyn misfolding and is neuroprotective, multiple compounds that restore phagocytosis impaired by αSyn overexpression, and a compound blocking cellular transmission of αSyn. Our studies demonstrate that drug-like small molecules that interact with native αSyn can impact a variety of its pathological processes. Thus, targeting the intrinsically disordered ensemble of αSyn offers a unique approach to the development of small molecule research tools and therapeutics for Parkinson's disease.