Steven Kim

AIMS/HYPOTHESIS: Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes. METHODS: The study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. RESULTS: Exome sequencing identified 70,182 polymorphisms with MAF >1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 × 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 × 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 × 10(-10)). CONCLUSIONS/INTERPRETATION: We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.

Abstract Open quantum systems that interact with a Markovian environment can be described by a Lindblad master equation. The generator of time-translation is given by a Liouvillian superoperator acting on the density matrix of the system. As the Fock space for a single bosonic mode is already infinite-dimensional, the diagonalization of the Liouvillian has to be done on the creation- and annihilation-superoperators, a process called ‘third quantization’. We propose a method to solve the Liouvillian for quadratic systems using a single symplectic transformation. We show that the non-Hermitian effective Hamiltonian of the system, next to incorporating the dynamics of the system, is a tool to analyze its symmetries. As an example, we use the effective Hamiltonian to formulate a -‘symmetry’ of an open system. We describe how the inclusion of source terms allows us to obtain the cumulant generating function for observables such as the photon current.

A chaotic light source is characterized by the fact that many independent emitters radiate photons with a random optical phase. This is similar compared to a tunnel junction where many independent channels are able to emit photons due to a coupling to an electromagnetic environment. However, in a recent experiment it has been observed that a tunnel junction can deviate from the expectation of chaotic light and is able to emit strongly correlated, superbunched photons. Motivated by this, we study the correlation of the radiation and show that the superbunching originates from the emission of multiple photons which is possible due to the quantization of charge.

Abstract Binary expression systems like the LexA-LexAop system provide a powerful experimental tool kit to study gene and tissue function in developmental biology, neurobiology and physiology. However, the number of well-defined LexA enhancer trap insertions remains limited. In this study, we present the molecular characterization and initial tissue expression analysis of nearly 100 novel StanEx LexA enhancer traps, derived from the StonEx 1 index line. This includes 76 insertions into novel, distinct gene loci not previously associated with enhancer traps or targeted LexA constructs. Additionally, our studies revealed evidence for selective transposase-dependent replacement of a previously-undetected KP element on chromosome III within the StanEx 1 genetic background during hybrid dysgenesis, suggesting a molecular basis for the over-representation of LexA insertions at the NK7.1 locus in our screen. Production and characterization of novel fly lines were performed by students and teachers in experiment-based genetics classes within a geographically diverse network of public and independent high schools. Thus, unique partnerships between secondary schools and university-based programs have produced and characterized novel genetic and molecular resources in Drosophila for open-source distribution, and provide paradigms for development of science education through experience-based pedagogy.