A SiGe BiCMOS Instrumentation Channel for Extreme Environment Applications

An instrumentation channel is designed, implemented, and tested in a 0.5-μm SiGe BiCMOS process. The circuit features a reconfigurable Wheatstone bridge network that interfaces an assortment of external sensors to signal processing circuits. Also, analog sampling is implemented in the channel using a flying capacitor configuration. The analog samples are digitized by a low-power multichannel A/D converter. Measurement results show that the instrumentation channel supports input signals up to 200 Hz and operates across a wide temperature range of -180°C to 125°C. This work demonstrates the use of a commercially available first generation SiGe BiCMOS process in designing circuits suitable for extreme environment applications

Rethinking Molecular Similarity: Comparing Compounds on the Basis of Biological Activity

Since the advent of high-throughput screening (HTS), there has been an urgent need for methods that facilitate the interrogation of large-scale chemical biology data to build a mode of action (MoA) hypothesis. This can be done either prior to the HTS by subset design of compounds with known MoA or post HTS by data annotation and mining. To enable this process, we developed a tool that compares compounds solely on the basis of their bioactivity: the chemical biological descriptor “high-throughput screening fingerprint” (HTS-FP). In the current embodiment, data are aggregated from 195 biochemical and cell-based assays developed at Novartis and can be used to identify bioactivity relationships among the in-house collection comprising ∼1.5 million compounds. We demonstrate the value of the HTS-FP for virtual screening and in particular scaffold hopping. HTS-FP outperforms state of the art methods in several aspects, retrieving bioactive compounds with remarkable chemical dissimilarity to a probe structure. We also apply HTS-FP for the design of screening subsets in HTS. Using retrospective data, we show that a biodiverse selection of plates performs significantly better than a chemically diverse selection of plates, both in terms of number of hits and diversity of chemotypes retrieved. This is also true in the case of hit expansion predictions using HTS-FP similarity. Sets of compounds clustered with HTS-FP are biologically meaningful, in the sense that these clusters enrich for genes and gene ontology (GO) terms, showing that compounds that are bioactively similar also tend to target proteins that operate together in the cell. HTS-FP are valuable not only because of their predictive power but mainly because they relate compounds solely on the basis of bioactivity, harnessing the accumulated knowledge of a high-throughput screening facility toward the understanding of how compounds interact with the proteome

Rethinking Molecular Similarity: Comparing Compounds on the Basis of Biological Activity

Since the advent of high-throughput screening (HTS), there has been an urgent need for methods that facilitate the interrogation of large-scale chemical biology data to build a mode of action (MoA) hypothesis. This can be done either prior to the HTS by subset design of compounds with known MoA or post HTS by data annotation and mining. To enable this process, we developed a tool that compares compounds solely on the basis of their bioactivity: the chemical biological descriptor “high-throughput screening fingerprint” (HTS-FP). In the current embodiment, data are aggregated from 195 biochemical and cell-based assays developed at Novartis and can be used to identify bioactivity relationships among the in-house collection comprising ∼1.5 million compounds. We demonstrate the value of the HTS-FP for virtual screening and in particular scaffold hopping. HTS-FP outperforms state of the art methods in several aspects, retrieving bioactive compounds with remarkable chemical dissimilarity to a probe structure. We also apply HTS-FP for the design of screening subsets in HTS. Using retrospective data, we show that a biodiverse selection of plates performs significantly better than a chemically diverse selection of plates, both in terms of number of hits and diversity of chemotypes retrieved. This is also true in the case of hit expansion predictions using HTS-FP similarity. Sets of compounds clustered with HTS-FP are biologically meaningful, in the sense that these clusters enrich for genes and gene ontology (GO) terms, showing that compounds that are bioactively similar also tend to target proteins that operate together in the cell. HTS-FP are valuable not only because of their predictive power but mainly because they relate compounds solely on the basis of bioactivity, harnessing the accumulated knowledge of a high-throughput screening facility toward the understanding of how compounds interact with the proteome

Shower development of particles with momenta from 1 to 10 GeV in the CALICE Scintillator-Tungsten HCAL

28 pages, 23 figures, 3 tablesLepton colliders are considered as options to complement and to extend the physics programme at the Large Hadron Collider. The Compact Linear Collider (CLIC) is an $e^+e^-$ collider under development aiming at centre-of-mass energies of up to 3 TeV. For experiments at CLIC, a hadron sampling calorimeter with tungsten absorber is proposed. Such a calorimeter provides sufficient depth to contain high-energy showers, while allowing a compact size for the surrounding solenoid. A fine-grained calorimeter prototype with tungsten absorber plates and scintillator tiles read out by silicon photomultipliers was built and exposed to particle beams at CERN. Results obtained with electrons, pions and protons of momenta up to 10 GeV are presented in terms of energy resolution and shower shape studies. The results are compared with several GEANT4 simulation models in order to assess the reliability of the Monte Carlo predictions relevant for a future experiment at CLIC