2,189 research outputs found
Evaluating the cytotoxicity of innate immune effector cells using the GrB ELISPOT assay
BACKGROUND: This study assessed the Granzyme B (GrB) ELISPOT as a viable alternative to the (51)Cr-release assay for measuring cytotoxic activity of innate immune effector cells. We strategically selected the GrB ELISPOT assay because GrB is a hallmark effector molecule of cell-mediated destruction of target cells. METHODS: We optimized the GrB ELISPOT assay using the human-derived TALL-104 cytotoxic cell line as effectors against K562 target cells. Titration studies were performed to assess whether the ELISPOT assay could accurately enumerate the number of GrB-secreting effector cells. TALL-104 were treated with various secretion inhibitors and utilized in the GrB ELISPOT to determine if GrB measured in the ELISPOT was due to degranulation of effector cells. Additionally, CD107a expression on effector cells after effector-target interaction was utilized to further confirm the mechanism of GrB release by TALL-104 and lymphokine-activated killer (LAK) cells. Direct comparisons between the GrB ELISPOT, the IFN-γ ELISPOT and the standard (51)Cr-release assays were made using human LAK cells. RESULTS: Titration studies demonstrated a strong correlation between the number of TALL-104 and LAK effector cells and the number of GrB spots per well. GrB secretion was detectable within 10 min of effector-target contact with optimal secretion observed at 3–4 h; in contrast, optimal IFN-γ secretion was not observed until 24 h. The protein secretion inhibitor, brefeldin A, did not inhibit the release of GrB but did abrogate IFN-γ production by TALL-104 cells. GrB secretion was abrogated by BAPTA-AM (1,2-bis-(2-aminophenoxy)ethane-N,N,N', N'-tetraacetic acid tetra(acetoxymethyl) ester), which sequesters intracellular Ca(2+), thereby preventing degranulation. The number of effector cells expressing the degranulation associated glycoprotein CD107a increased after interaction with target cells and correlated with the stimulated release of GrB measured in the ELISPOT assay. CONCLUSIONS: Because of its high sensitivity and ability to estimate cytotoxic effector cell frequency, the GrB ELISPOT assay is a viable alternative to the (51)Cr-release assay to measure MHC non-restricted cytotoxic activity of innate immune cells. Compared to the IFN-γ ELISPOT assay, the GrB ELISPOT may be a more direct measure of cytotoxic cell activity. Because GrB is one of the primary effector molecules in natural killer (NK) cell-mediated killing, detection and enumeration of GrB secreting effector cells can provide valuable insight with regards to innate immunological responses
Nonlinear Dynamics in Ecosystem Response to Climatic Change: Case Studies and Policy Implications
Many biological, hydrological, and geological processes are interactively linked in ecosystems. These ecological phenomena normally vary within bounded ranges, but rapid, nonlinear changes to markedly different conditions can be triggered by even small differences if threshold values are exceeded. Intrinsic and extrinsic ecological thresholds can lead to effects that cascade among systems, precluding accurate modeling and prediction of system response to climate change. Ten case studies from North America illustrate how changes in climate can lead to rapid, threshold-type responses within ecological communities; the case studies also highlight the role of human activities that alter the rate or direction of system response to climate change. Understanding and anticipating nonlinear dynamics are important aspects of adaptation planning since responses of biological resources to changes in the physical climate system are not necessarily proportional and sometimes, as in the case of complex ecological systems, inherently nonlinear
Sectoral Impacts of Invasive Species in the United States and Approaches to Management
Invasive species have a major effect on many sectors of the U.S. economy and on the well-being of its citizens. Their presence impacts animal and human health, military readiness, urban vegetation and infrastructure, water, energy and transportations systems, and indigenous peoples in the United States (Table 9.1). They alter bio-physical systems and cultural practices and require significant public and private expenditure for control. This chapter provides examples of the impacts to human systems and explains mechanisms of invasive species’ establishment and spread within sectors of the U.S. economy. The chapter is not intended to be comprehensive but rather to provide insight into the range and severity of impacts. Examples provide context for ongoing Federal programs and initiatives and support State and private efforts to prevent the introduction and spread of invasive species and eradicate and control established invasive species
Accountability in the East Asian economic miracle, crisis and recovery
Despite claims that accountability enables 'good governance' proper, its specific origins, character and limitations are not yet fully clear. In order to explicate the nature of accountability better this paper will, therefore, formulate and apply its own comparative framework to the case of the East Asian economic miracle, crisis and recovery in particular. In so doing it finds that, even when accountability emerged as a mid-crisis issue that was dramatically reconfigured for any due recovery later, it was not itself then sufficiently explicated for all the implications and consequences to be realized fully. Once it is explicated more fully, however, the further implications and consequences of changing accountability for economic governance question precisely what is to be expected from accountability per se
Tracker Operation and Performance at the Magnet Test and Cosmic Challenge
During summer 2006 a fraction of the CMS silicon strip tracker was operated in a comprehensive slice test called the Magnet Test and Cosmic Challenge (MTCC). At the MTCC, cosmic rays detected in the muon chambers were used to trigger the readout of all CMS sub-detectors in the general data acquisition system and in the presence of the 4 T magnetic field produced by the CMS superconducting solenoid. This document describes the operation of the Tracker hardware and software prior, during and after data taking. The performance of the detector as resulting from the MTCC data analysis is also presented
Measurement-Induced State Transitions in a Superconducting Qubit: Within the Rotating Wave Approximation
Superconducting qubits typically use a dispersive readout scheme, where a
resonator is coupled to a qubit such that its frequency is qubit-state
dependent. Measurement is performed by driving the resonator, where the
transmitted resonator field yields information about the resonator frequency
and thus the qubit state. Ideally, we could use arbitrarily strong resonator
drives to achieve a target signal-to-noise ratio in the shortest possible time.
However, experiments have shown that when the average resonator photon number
exceeds a certain threshold, the qubit is excited out of its computational
subspace, which we refer to as a measurement-induced state transition. These
transitions degrade readout fidelity, and constitute leakage which precludes
further operation of the qubit in, for example, error correction. Here we study
these transitions using a transmon qubit by experimentally measuring their
dependence on qubit frequency, average photon number, and qubit state, in the
regime where the resonator frequency is lower than the qubit frequency. We
observe signatures of resonant transitions between levels in the coupled
qubit-resonator system that exhibit noisy behavior when measured repeatedly in
time. We provide a semi-classical model of these transitions based on the
rotating wave approximation and use it to predict the onset of state
transitions in our experiments. Our results suggest the transmon is excited to
levels near the top of its cosine potential following a state transition, where
the charge dispersion of higher transmon levels explains the observed noisy
behavior of state transitions. Moreover, occupation in these higher energy
levels poses a major challenge for fast qubit reset
Overcoming leakage in scalable quantum error correction
Leakage of quantum information out of computational states into higher energy
states represents a major challenge in the pursuit of quantum error correction
(QEC). In a QEC circuit, leakage builds over time and spreads through
multi-qubit interactions. This leads to correlated errors that degrade the
exponential suppression of logical error with scale, challenging the
feasibility of QEC as a path towards fault-tolerant quantum computation. Here,
we demonstrate the execution of a distance-3 surface code and distance-21
bit-flip code on a Sycamore quantum processor where leakage is removed from all
qubits in each cycle. This shortens the lifetime of leakage and curtails its
ability to spread and induce correlated errors. We report a ten-fold reduction
in steady-state leakage population on the data qubits encoding the logical
state and an average leakage population of less than
throughout the entire device. The leakage removal process itself efficiently
returns leakage population back to the computational basis, and adding it to a
code circuit prevents leakage from inducing correlated error across cycles,
restoring a fundamental assumption of QEC. With this demonstration that leakage
can be contained, we resolve a key challenge for practical QEC at scale.Comment: Main text: 7 pages, 5 figure
Combined Forward-Backward Asymmetry Measurements in Top-Antitop Quark Production at the Tevatron
The CDF and D0 experiments at the Fermilab Tevatron have measured the asymmetry between yields of forward- and backward-produced top and antitop quarks based on their rapidity difference and the asymmetry between their decay leptons. These measurements use the full data sets collected in proton-antiproton collisions at a center-of-mass energy of TeV. We report the results of combinations of the inclusive asymmetries and their differential dependencies on relevant kinematic quantities. The combined inclusive asymmetry is . The combined inclusive and differential asymmetries are consistent with recent standard model predictions
Measurement-induced entanglement and teleportation on a noisy quantum processor
Measurement has a special role in quantum theory: by collapsing the
wavefunction it can enable phenomena such as teleportation and thereby alter
the "arrow of time" that constrains unitary evolution. When integrated in
many-body dynamics, measurements can lead to emergent patterns of quantum
information in space-time that go beyond established paradigms for
characterizing phases, either in or out of equilibrium. On present-day NISQ
processors, the experimental realization of this physics is challenging due to
noise, hardware limitations, and the stochastic nature of quantum measurement.
Here we address each of these experimental challenges and investigate
measurement-induced quantum information phases on up to 70 superconducting
qubits. By leveraging the interchangeability of space and time, we use a
duality mapping, to avoid mid-circuit measurement and access different
manifestations of the underlying phases -- from entanglement scaling to
measurement-induced teleportation -- in a unified way. We obtain finite-size
signatures of a phase transition with a decoding protocol that correlates the
experimental measurement record with classical simulation data. The phases
display sharply different sensitivity to noise, which we exploit to turn an
inherent hardware limitation into a useful diagnostic. Our work demonstrates an
approach to realize measurement-induced physics at scales that are at the
limits of current NISQ processors
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