Bistability in Apoptosis by Receptor Clustering

Apoptosis is a highly regulated cell death mechanism involved in many physiological processes. A key component of extrinsically activated apoptosis is the death receptor Fas, which, on binding to its cognate ligand FasL, oligomerize to form the death-inducing signaling complex. Motivated by recent experimental data, we propose a mathematical model of death ligand-receptor dynamics where FasL acts as a clustering agent for Fas, which form locally stable signaling platforms through proximity-induced receptor interactions. Significantly, the model exhibits hysteresis, providing an upstream mechanism for bistability and robustness. At low receptor concentrations, the bistability is contingent on the trimerism of FasL. Moreover, irreversible bistability, representing a committed cell death decision, emerges at high concentrations, which may be achieved through receptor pre-association or localization onto membrane lipid rafts. Thus, our model provides a novel theory for these observed biological phenomena within the unified context of bistability. Importantly, as Fas interactions initiate the extrinsic apoptotic pathway, our model also suggests a mechanism by which cells may function as bistable life/death switches independently of any such dynamics in their downstream components. Our results highlight the role of death receptors in deciding cell fate and add to the signal processing capabilities attributed to receptor clustering.Comment: Accepted by PLoS Comput Bio

Global Analysis of Dynamical Decision-Making Models through Local Computation around the Hidden Saddle

Bistable dynamical switches are frequently encountered in mathematical modeling of biological systems because binary decisions are at the core of many cellular processes. Bistable switches present two stable steady-states, each of them corresponding to a distinct decision. In response to a transient signal, the system can flip back and forth between these two stable steady-states, switching between both decisions. Understanding which parameters and states affect this switch between stable states may shed light on the mechanisms underlying the decision-making process. Yet, answering such a question involves analyzing the global dynamical (i.e., transient) behavior of a nonlinear, possibly high dimensional model. In this paper, we show how a local analysis at a particular equilibrium point of bistable systems is highly relevant to understand the global properties of the switching system. The local analysis is performed at the saddle point, an often disregarded equilibrium point of bistable models but which is shown to be a key ruler of the decision-making process. Results are illustrated on three previously published models of biological switches: two models of apoptosis, the programmed cell death and one model of long-term potentiation, a phenomenon underlying synaptic plasticity

Searching for Heavy Dark Matter near the Planck Mass with XENON1T

Multiple viable theoretical models predict heavy dark matter particles with a mass close to the Planck mass, a range relatively unexplored by current experimental measurements. We use 219.4 days of data collected with the XENON1T experiment to conduct a blind search for signals from multiply interacting massive particles (MIMPs). Their unique track signature allows a targeted analysis with only 0.05 expected background events from muons. Following unblinding, we observe no signal candidate events. This Letter places strong constraints on spin-independent interactions of dark matter particles with a mass between 1×10$^{12}$ and 2×10$^{17}$  GeV/c$^2$. In addition, we present the first exclusion limits on spin-dependent MIMP-neutron and MIMP-proton cross sections for dark matter particles with masses close to the Planck scale

Detector signal characterization with a Bayesian network in XENONnT

We developed a detector signal characterization model based on a Bayesian network trained on the waveform attributes generated by a dual-phase xenon time projection chamber. By performing inference on the model, we produced a quantitative metric of signal characterization and demonstrate that this metric can be used to determine whether a detector signal is sourced from a scintillation or an ionization process. We describe the method and its performance on electronic-recoil (ER) data taken during the first science run of the XENONnT dark matter experiment. We demonstrate the first use of a Bayesian network in a waveform-based analysis of detector signals. This method resulted in a 3% increase in ER event-selection efficiency with a simultaneously effective rejection of events outside of the region of interest. The findings of this analysis are consistent with the previous analysis from XENONnT, namely a background-only fit of the ER data

First Dark Matter Search with Nuclear Recoils from the XENONnT Experiment

We report on the first search for nuclear recoils from dark matter in the form of weakly interacting massive particles (WIMPs) with the XENONnT experiment, which is based on a two-phase time projection chamber with a sensitive liquid xenon mass of 5.9 ton. During the (1.09±0.03)  ton yr exposure used for this search, the intrinsic $^{85}$Kr and $^{222}$Rn concentrations in the liquid target are reduced to unprecedentedly low levels, giving an electronic recoil background rate of (15.8±1.3)  events/ton yr keV in the region of interest. A blind analysis of nuclear recoil events with energies between 3.3 and 60.5 keV finds no significant excess. This leads to a minimum upper limit on the spin-independent WIMP-nucleon cross section of 2.58×10$^{47}$  cm$^2$ for a WIMP mass of 28  GeV/c$^2$ at 90% confidence level. Limits for spin-dependent interactions are also provided. Both the limit and the sensitivity for the full range of WIMP masses analyzed here improve on previous results obtained with the XENON1T experiment for the same exposure

Cosmogenic background simulations for neutrinoless double beta decay with the DARWIN observatory at various underground sites

Xenon dual-phase time projections chambers (TPCs) have proven to be a successful technology in studying physical phenomena that require low-background conditions. With 40t of liquid xenon (LXe) in the TPC baseline design, DARWIN will have a high sensitivity for the detection of particle dark matter, neutrinoless double beta decay (0 ν β β), and axion-like particles (ALPs). Although cosmic muons are a source of background that cannot be entirely eliminated, they may be greatly diminished by placing the detector deep underground. In this study, we used Monte Carlo simulations to model the cosmogenic background expected for the DARWIN observatory at four underground laboratories: Laboratori Nazionali del Gran Sasso (LNGS), Sanford Underground Research Facility (SURF), Laboratoire Souterrain de Modane (LSM) and SNOLAB. We present here the results of simulations performed to determine the production rate of 137 Xe, the most crucial isotope in the search for 0 ν β β of 136 Xe. Additionally, we explore the contribution that other muon-induced spallation products, such as other unstable xenon isotopes and tritium, may have on the cosmogenic background

Searching for Heavy Dark Matter near the Planck Mass with XENON1T

Multiple viable theoretical models predict heavy dark matter particles with a mass close to the Planck mass, a range relatively unexplored by current experimental measurements. We use 219.4 days of data collected with the XENON1T experiment to conduct a blind search for signals from Multiply-Interacting Massive Particles (MIMPs). Their unique track signature allows a targeted analysis with only 0.05 expected background events from muons. Following unblinding, we observe no signal candidate events. This work places strong constraints on spin-independent interactions of dark matter particles with a mass between 1$\times$10$^{12}\,$GeV/c$^2$ and 2$\times$10$^{17}\,$GeV/c$^2$. In addition, we present the first exclusion limits on spin-dependent MIMP-neutron and MIMP-proton cross-sections for dark matter particles with masses close to the Planck scale.Comment: 7 pages, 6 figure

Cosmogenic background simulations for the DARWIN observatory at different underground locations

Xenon dual-phase time projections chambers (TPCs) have proven to be a successful technology in studying physical phenomena that require low-background conditions. With 40t of liquid xenon (LXe) in the TPC baseline design, DARWIN will have a high sensitivity for the detection of particle dark matter, neutrinoless double beta decay ($0\nu\beta\beta$), and axion-like particles (ALPs). Although cosmic muons are a source of background that cannot be entirely eliminated, they may be greatly diminished by placing the detector deep underground. In this study, we used Monte Carlo simulations to model the cosmogenic background expected for the DARWIN observatory at four underground laboratories: Laboratori Nazionali del Gran Sasso (LNGS), Sanford Underground Research Facility (SURF), Laboratoire Souterrain de Modane (LSM) and SNOLAB. We determine the production rates of unstable xenon isotopes and tritium due to muon-included neutron fluxes and muon-induced spallation. These are expected to represent the dominant contributions to cosmogenic backgrounds and thus the most relevant for site selection

Search for events in XENON1T associated with Gravitational Waves

We perform a blind search for particle signals in the XENON1T dark matter detector that occur close in time to gravitational wave signals in the LIGO and Virgo observatories. No particle signal is observed in the nuclear recoil, electronic recoil, CE$\nu$NS, and S2-only channels within $\pm$ 500 seconds of observations of the gravitational wave signals GW170104, GW170729, GW170817, GW170818, and GW170823. We use this null result to constrain mono-energetic neutrinos and Beyond Standard Model particles emitted in the closest coalescence GW170817, a binary neutron star merger. We set new upper limits on the fluence (time-integrated flux) of coincident neutrinos down to 17 keV at 90% confidence level. Furthermore, we constrain the product of coincident fluence and cross section of Beyond Standard Model particles to be less than $10^{-29}$ cm$^2$/cm$^2$ in the [5.5-210] keV energy range at 90% confidence level

Design and performance of the field cage for the XENONnT experiment

The precision in reconstructing events detected in a dual-phase time projection chamber depends on an homogeneous and well understood electric field within the liquid target. In the XENONnT TPC the field homogeneity is achieved through a double-array field cage, consisting of two nested arrays of field shaping rings connected by an easily accessible resistor chain. Rather than being connected to the gate electrode, the topmost field shaping ring is independently biased, adding a degree of freedom to tune the electric field during operation. Two-dimensional finite element simulations were used to optimize the field cage, as well as its operation. Simulation results were compared to $^{83m} Kr$ calibration data. This comparison indicates an accumulation of charge on the panels of the TPC which is constant over time, as no evolution of the reconstructed position distribution of events is observed. The simulated electric field was then used to correct the charge signal for the field dependence of the charge yield. This correction resolves the inconsistent measurement of the drift electron lifetime when using different calibrations sources and different field cage tuning voltages