164 research outputs found

    Dynamics of Simple Balancing Models with State Dependent Switching Control

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    Time-delayed control in a balancing problem may be a nonsmooth function for a variety of reasons. In this paper we study a simple model of the control of an inverted pendulum by either a connected movable cart or an applied torque for which the control is turned off when the pendulum is located within certain regions of phase space. Without applying a small angle approximation for deviations about the vertical position, we see structurally stable periodic orbits which may be attracting or repelling. Due to the nonsmooth nature of the control, these periodic orbits are born in various discontinuity-induced bifurcations. Also we show that a coincidence of switching events can produce complicated periodic and aperiodic solutions.Comment: 36 pages, 12 figure

    A chemical probe unravels the reactive proteome of health-associated catechols

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    Catechol-containing natural products are common constituents of foods, drinks, and drugs. Natural products carrying this motif are often associated with beneficial biological effects such as anticancer activity and neuroprotection. However, the molecular mode of action behind these properties is poorly understood. Here, we apply a mass spectrometry-based competitive chemical proteomics approach to elucidate the target scope of catechol-containing bioactive molecules from diverse foods and drugs. Inspired by the protein reactivity of catecholamine neurotransmitters, we designed and synthesised a broadly reactive minimalist catechol chemical probe based on dopamine. Initial labelling experiments in live human cells demonstrated broad protein binding by the probe, which was largely outcompeted by its parent compound dopamine. Next, we investigated the competition profile of a selection of biologically relevant catechol-containing substances. With this approach, we characterised the protein reactivity and the target scope of dopamine and ten biologically relevant catechols. Strikingly, proteins associated with the endoplasmic reticulum (ER) were among the main targets. ER stress assays in the presence of reactive catechols revealed an activation of the unfolded protein response (UPR). The UPR is highly relevant in oncology and cellular resilience, which may provide an explanation of the health-promoting effects attributed to many catechol-containing natural products.Molecular Physiolog

    A chemical proteomic strategy reveals inhibitors of lipoate salvage in bacteria and parasites

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    The development of novel anti-infectives requires unprecedented strategies targeting pathways which are solely present in pathogens but absent in humans. Following this principle, we developed inhibitors of lipoic acid (LA) salvage, a crucial pathway for the survival of LA auxotrophic bacteria and parasites but non-essential in human cells. An LA-based probe was selectively transferred onto substrate proteins via lipoate protein ligase (LPL) in intact cells, and their binding sites were determined by mass spectrometry. Probe labeling served as a proxy of LPL activity, enabling in situ screenings for cell-permeable LPL inhibitors. Profiling a focused compound library revealed two substrate analogs (LAMe and C3) as inhibitors, which were further validated by binding studies and co-crystallography. Importantly, LAMe exhibited low toxicity in human cells and achieved killing of Plasmodium falciparum in erythrocytes with an EC50 value of 15 μM, making it the most effective LPL inhibitor reported to date.Molecular Physiolog

    Mechanical stability of the CMS strip tracker measured with a laser alignment system

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    Search for massive resonances decaying in to WW,WZ or ZZ bosons in proton-proton collisions at root s=13 TeV

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    Search for R-parity violating supersymmetry with displaced vertices in proton-proton collisions at root s=8 TeV

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    Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

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    Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

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    Search for direct production of supersymmetric partners of the top quark in the all-jets final state in proton-proton collisions at root s=13 TeV

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    Measurement of the inclusive 3-jet production differential cross section in proton-proton collisions at 7 TeV and determination of the strong coupling constant in the TeV range

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    This paper presents a measurement of the inclusive 3-jet production differential cross section at a proton–proton centre-of-mass energy of 7 TeV using data corresponding to an integrated luminosity of 5 fb-1 collected with the CMS detector. The analysis is based on the three jets with the highest transverse momenta. The cross section is measured as a function of the invariant mass of the three jets in a range of 445–3270 GeV and in two bins of the maximum rapidity of the jets up to a value of 2. A comparison between the measurement and the prediction from perturbative QCD at next-to-leading order is performed. Within uncertainties, data and theory are in agreement. The sensitivity of the observable to the strong coupling constant αS is studied. A fit to all data points with 3-jet masses larger than 664 GeV gives a value of the strong coupling constant of αS(MZ)=0.1171±0.0013(exp)-0.0047+0.0073(theo)
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