@article{5816, abstract = {Solid-state qubit manipulation and read-out fidelities are reaching fault-tolerance, but quantum error correction requires millions of physical qubits and therefore a scalable quantum computer architecture. To solve signal-line bandwidth and fan-out problems, microwave sources required for qubit manipulation might be embedded close to the qubit chip, typically operating at temperatures below 4 K. Here, we perform the first low temperature measurements of a 130 nm BiCMOS based SiGe voltage controlled oscillator at cryogenic temperature. We determined the frequency and output power dependence on temperature and magnetic field up to 5 T and measured the temperature influence on its noise performance. The device maintains its full functionality from 300 K to 4 K. The carrier frequency at 4 K increases by 3% with respect to the carrier frequency at 300 K, and the output power at 4 K increases by 10 dB relative to the output power at 300 K. The frequency tuning range of approximately 20% remains unchanged between 300 K and 4 K. In an in-plane magnetic field of 5 T, the carrier frequency shifts by only 0.02% compared to the frequency at zero magnetic field.}, author = {Hollmann, Arne and Jirovec, Daniel and Kucharski, Maciej and Kissinger, Dietmar and Fischer, Gunter and Schreiber, Lars R.}, issn = {00346748}, journal = {Review of Scientific Instruments}, number = {11}, publisher = {AIP Publishing}, title = {{30 GHz-voltage controlled oscillator operating at 4 K}}, doi = {10.1063/1.5038258}, volume = {89}, year = {2018}, } @phdthesis{6263, abstract = {Antibiotic resistance can emerge spontaneously through genomic mutation and render treatment ineffective. To counteract this process, in addition to the discovery and description of resistance mechanisms,a deeper understanding of resistanceevolvabilityand its determinantsis needed. To address this challenge, this thesisuncoversnew genetic determinants of resistance evolvability using a customized robotic setup, exploressystematic ways in which resistance evolution is perturbed due to dose-responsecharacteristics of drugs and mutation rate differences,and mathematically investigates the evolutionary fate of one specific type of evolvability modifier -a stress-induced mutagenesis allele.We find severalgenes which strongly inhibit or potentiate resistance evolution. In order to identify them, we first developedan automated high-throughput feedback-controlled protocol whichkeeps the population size and selection pressure approximately constant for hundreds of cultures by dynamically re-diluting the cultures and adjusting the antibiotic concentration. We implementedthis protocol on a customized liquid handling robot and propagated 100 different gene deletion strains of Escherichia coliin triplicate for over 100 generations in tetracycline and in chloramphenicol, and comparedtheir adaptation rates.We find a diminishing returns pattern, where initially sensitive strains adapted more compared to less sensitive ones. Our data uncover that deletions of certain genes which do not affect mutation rate,including efflux pump components, a chaperone and severalstructural and regulatory genes can strongly and reproducibly alterresistance evolution. Sequencing analysis of evolved populations indicates that epistasis with resistance mutations is the most likelyexplanation. This work could inspire treatment strategies in which targeted inhibitors of evolvability mechanisms will be given alongside antibiotics to slow down resistance evolution and extend theefficacy of antibiotics.We implemented astochasticpopulation genetics model, toverifyways in which general properties, namely, dose-response characteristics of drugs and mutation rates, influence evolutionary dynamics. In particular, under the exposure to antibiotics with shallow dose-response curves,bacteria have narrower distributions of fitness effects of new mutations. We show that in silicothis also leads to slower resistance evolution. We see and confirm with experiments that increased mutation rates, apart from speeding up evolution, also leadto high reproducibility of phenotypic adaptation in a context of continually strong selection pressure.Knowledge of these patterns can aid in predicting the dynamics of antibiotic resistance evolutionand adapting treatment schemes accordingly.Focusing on a previously described type of evolvability modifier –a stress-induced mutagenesis allele –we find conditions under which it can persist in a population under periodic selectionakin to clinical treatment. We set up a deterministic infinite populationcontinuous time model tracking the frequencies of a mutator and resistance allele and evaluate various treatment schemes in how well they maintain a stress-induced mutator allele. In particular,a high diversity of stresses is crucial for the persistence of the mutator allele. This leads to a general trade-off where exactly those diversifying treatment schemes which are likely to decrease levels of resistance could lead to stronger selection of highly evolvable genotypes.In the long run, this work will lead to a deeper understanding of the genetic and cellular mechanisms involved in antibiotic resistance evolution and could inspire new strategies for slowing down its rate. }, author = {Lukacisinova, Marta}, issn = {2663-337X}, pages = {91}, publisher = {Institute of Science and Technology Austria}, title = {{Genetic determinants of antibiotic resistance evolution}}, doi = {10.15479/AT:ISTA:th1072}, year = {2018}, } @article{544, abstract = {Drosophila melanogaster plasmatocytes, the phagocytic cells among hemocytes, are essential for immune responses, but also play key roles from early development to death through their interactions with other cell types. They regulate homeostasis and signaling during development, stem cell proliferation, metabolism, cancer, wound responses and aging, displaying intriguing molecular and functional conservation with vertebrate macrophages. Given the relative ease of genetics in Drosophila compared to vertebrates, tools permitting visualization and genetic manipulation of plasmatocytes and surrounding tissues independently at all stages would greatly aid in fully understanding these processes, but are lacking. Here we describe a comprehensive set of transgenic lines that allow this. These include extremely brightly fluorescing mCherry-based lines that allow GAL4-independent visualization of plasmatocyte nuclei, cytoplasm or actin cytoskeleton from embryonic Stage 8 through adulthood in both live and fixed samples even as heterozygotes, greatly facilitating screening. These lines allow live visualization and tracking of embryonic plasmatocytes, as well as larval plasmatocytes residing at the body wall or flowing with the surrounding hemolymph. With confocal imaging, interactions of plasmatocytes and inner tissues can be seen in live or fixed embryos, larvae and adults. They permit efficient GAL4-independent FACS analysis/sorting of plasmatocytes throughout life. To facilitate genetic analysis of reciprocal signaling, we have also made a plasmatocyte-expressing QF2 line that in combination with extant GAL4 drivers allows independent genetic manipulation of both plasmatocytes and surrounding tissues, and a GAL80 line that blocks GAL4 drivers from affecting plasmatocytes, both of which function from the early embryo to the adult.}, author = {György, Attila and Roblek, Marko and Ratheesh, Aparna and Valosková, Katarina and Belyaeva, Vera and Wachner, Stephanie and Matsubayashi, Yutaka and Sanchez Sanchez, Besaiz and Stramer, Brian and Siekhaus, Daria E}, journal = {G3: Genes, Genomes, Genetics}, number = {3}, pages = {845 -- 857}, publisher = {Genetics Society of America}, title = {{Tools allowing independent visualization and genetic manipulation of Drosophila melanogaster macrophages and surrounding tissues}}, doi = {10.1534/g3.117.300452}, volume = {8}, year = {2018}, } @article{612, abstract = {Metabotropic GABAB receptors mediate slow inhibitory effects presynaptically and postsynaptically through the modulation of different effector signalling pathways. Here, we analysed the distribution of GABAB receptors using highly sensitive SDS-digested freeze-fracture replica labelling in mouse cerebellar Purkinje cells. Immunoreactivity for GABAB1 was observed on presynaptic and, more abundantly, on postsynaptic compartments, showing both scattered and clustered distribution patterns. Quantitative analysis of immunoparticles revealed a somato-dendritic gradient, with the density of immunoparticles increasing 26-fold from somata to dendritic spines. To understand the spatial relationship of GABAB receptors with two key effector ion channels, the G protein-gated inwardly rectifying K+ (GIRK/Kir3) channel and the voltage-dependent Ca2+ channel, biochemical and immunohistochemical approaches were performed. Co-immunoprecipitation analysis demonstrated that GABAB receptors co-assembled with GIRK and CaV2.1 channels in the cerebellum. Using double-labelling immunoelectron microscopic techniques, co-clustering between GABAB1 and GIRK2 was detected in dendritic spines, whereas they were mainly segregated in the dendritic shafts. In contrast, co-clustering of GABAB1 and CaV2.1 was detected in dendritic shafts but not spines. Presynaptically, although no significant co-clustering of GABAB1 and GIRK2 or CaV2.1 channels was detected, inter-cluster distance for GABAB1 and GIRK2 was significantly smaller in the active zone than in the dendritic shafts, and that for GABAB1 and CaV2.1 was significantly smaller in the active zone than in the dendritic shafts and spines. Thus, GABAB receptors are associated with GIRK and CaV2.1 channels in different subcellular compartments. These data provide a better framework for understanding the different roles played by GABAB receptors and their effector ion channels in the cerebellar network.}, author = {Luján, Rafael and Aguado, Carolina and Ciruela, Francisco and Cózar, Javier and Kleindienst, David and De La Ossa, Luis and Bettler, Bernhard and Wickman, Kevin and Watanabe, Masahiko and Shigemoto, Ryuichi and Fukazawa, Yugo}, journal = {Brain Structure and Function}, number = {3}, pages = {1565 -- 1587}, publisher = {Springer}, title = {{Differential association of GABAB receptors with their effector ion channels in Purkinje cells}}, doi = {10.1007/s00429-017-1568-y}, volume = {223}, year = {2018}, } @article{21, abstract = {Parvalbumin-positive (PV+) GABAergic interneurons in hippocampal microcircuits are thought to play a key role in several higher network functions, such as feedforward and feedback inhibition, network oscillations, and pattern separation. Fast lateral inhibition mediated by GABAergic interneurons may implement a winner-takes-all mechanism in the hippocampal input layer. However, it is not clear whether the functional connectivity rules of granule cells (GCs) and interneurons in the dentate gyrus are consistent with such a mechanism. Using simultaneous patch-clamp recordings from up to seven GCs and up to four PV+ interneurons in the dentate gyrus, we find that connectivity is structured in space, synapse-specific, and enriched in specific disynaptic motifs. In contrast to the neocortex, lateral inhibition in the dentate gyrus (in which a GC inhibits neighboring GCs via a PV+ interneuron) is ~ 10-times more abundant than recurrent inhibition (in which a GC inhibits itself). Thus, unique connectivity rules may enable the dentate gyrus to perform specific higher-order computations}, author = {Espinoza Martinez, Claudia and Guzmán, José and Zhang, Xiaomin and Jonas, Peter M}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, title = {{Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus}}, doi = {10.1038/s41467-018-06899-3}, volume = {9}, year = {2018}, }