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Studies over the last decade have identified differences in cancer gene expression that cannot be explained by coding sequences or promoter variations. The effect of transcriptional enhancers, on the other hand, remains unclear due to the lack of an effective way to link enhancers with their controlled genes. Recently, we discovered a class of inter-tumor, inter-patient DNA methylation variations in putative enhancers that predict changes in gene expression levels with much greater power than promoter or sequence analyses. I will describe our efforts to determine if changes in enhancer methylation form part of the genomic basis of cancer.

Clouds play a major role for the hydrological cycle, the radiation budget and climate on Earth. They are also the largest factor of uncertainty in the scientific understanding and prediction of climate change. The CLOUD experiment at CERN allows to study aerosol and cloud formation under atmospheric conditions at a new level of precision. A focus of investigations are ion-induced aerosol formation processes using an elementary particle beam from CERN. Here, the potential role of galactic cosmic rays - and their modulation by the sun - for aerosols, clouds and climate is studied. The role of ionization for aerosol formation by different chemical systems of natural and anthropogenic origin is quantied. The experiments therefore yield a new understanding of pre-industrial and present-day aerosol sources and their influences on clouds and climate. Most recently, an important new mechanism based on purely biogenic precursor compounds was discovered and its role for climate was assessed. Furthermore, the results from many experiments performed over the past years were parameterized and combined in a global model to predict the role of different particle formation mechanisms in the different regions of the atmosphere. The talk presents an introduction on the role of aerosols and clouds for climate, an overview of the CLOUD chamber at CERN, and of the fi ndings and implications from recent experiments.

In this talk, I will discuss the planar behavior displayed by 4-dimensional Lagrangian N=2 SCFTs with simple gauge group and argue that in this limit most characteristics of the theories are governed by a universal equation with a single tunable parameter. Remarkably, the same parameter discriminates whether their holographic dual admits a conventional supergravity limit.

At GNF, we have been developing and implementing high throughput miniaturized assays and robotic systems to enable drug discovery for over 15 years. This presentation will review how our platform systems have adapted to and incorporated the latest scientific and technical advancements. Our flagship high throughput screening systems, capable of running hundreds of thousands of compounds per day against cellular or biochemical assays, continue to demonstrate their effectiveness. We have continued to expand the utility of GNF-built automation, as well as other commercially available technologies, to enable cost effective and rapid cell-based profiling of small molecules as well as biologics. In addition, this approach has allowed scientists to run primary cell assays on a scale not otherwise practical. Examples will include instruments and automation to greatly accelerate high-content phenotypic assays and flow cytometry. The latest advancements in reagent dispensing, detection and robotics will further the deployment of these technologies into areas such as highly multiplexed transcriptional readouts and Next Gen Sequencing.

Mammalian brains store and update quantitative internal variables. Primates and rodents, for example, have an internal sense of whether they are 1 or 10 meters away from a landmark and whether a ripe fruit is twice or four times as appetizing as a less ripe counterpart. Such quantitative internal signals are the basis of cognitive function, however, our understanding of how the brain stores and updates these variables remains fragmentary. In this talk, I will discuss imaging and perturbation experiments in tethered, walking Drosophila. The goal of these experiments is to determine how internal variables are calculated by the tiny Drosophila brain and how these variables influence behavior. Specifically, in the Drosophila central complex a set of heading neurons have been described, whose activity tracks the fly’s orientation, similar to head direction cells in rodents. However, the circuit architecture that gives rise to these orientation tracking properties remains largely unknown in any species. I will describe a set of clockwise- and counterclockwise-shifting neurons whose wiring and calcium dynamics provide a means to rotate the heading system’s angular estimate over time. Shifting neurons are required for the heading system to properly track the fly's movements in the dark, and, their stimulation induces a rotation of the heading signal in the expected direction and by the expected amount. The central features of this circuit are analogous to models proposed for head-direction cells in rodents and may thus inform how neural systems, in general, perform addition.