80 research outputs found
Final Report: 9-B English Service-learning Evaluation, Moorhead High School, Moorhead, Minnesota
Mark Jensen, English faculty at MHS offered his service-learning program for an evaluation. This evaluation was initiated by Jeanie Jacobs consequent to the conditions of a grant she received; the structure of this evaluation evolved over several team meetings between Jensen, Ann Larson (District 152 Director of Community Service-learning) and myself
Polyunsaturated fatty acids inhibit a pentameric ligand-gated ion channel through one of two binding sites
Polyunsaturated fatty acids (PUFAs) inhibit pentameric ligand-gated ion channels (pLGICs) but the mechanism of inhibition is not well understood. The PUFA, docosahexaenoic acid (DHA), inhibits agonist responses of the pLGIC, ELIC, more effectively than palmitic acid, similar to the effects observed in the GAB
Emergent Randomness and Benchmarking from Many-Body Quantum Chaos
Chaotic quantum many-body dynamics typically lead to relaxation of local
observables. In this process, known as quantum thermalization, a subregion
reaches a thermal state due to quantum correlations with the remainder of the
system, which acts as an intrinsic bath. While the bath is generally assumed to
be unobserved, modern quantum science experiments have the ability to track
both subsystem and bath at a microscopic level. Here, by utilizing this
ability, we discover that measurement results associated with small subsystems
exhibit universal random statistics following chaotic quantum many-body
dynamics, a phenomenon beyond the standard paradigm of quantum thermalization.
We explain these observations with an ensemble of pure states, defined via
correlations with the bath, that dynamically acquires a close to random
distribution. Such random ensembles play an important role in quantum
information science, associated with quantum supremacy tests and device
verification, but typically require highly-engineered, time-dependent control
for their preparation. In contrast, our approach uncovers random ensembles
naturally emerging from evolution with a time-independent Hamiltonian. As an
application of this emergent randomness, we develop a benchmarking protocol
which estimates the many-body fidelity during generic chaotic evolution and
demonstrate it using our Rydberg quantum simulator. Our work has wide ranging
implications for the understanding of quantum many-body chaos and
thermalization in terms of emergent randomness and at the same time paves the
way for applications of this concept in a much wider context.Comment: JC and ALS contributed equally to this wor
Two Rare Magnetic Cataclysmic Variables with Extreme Cyclotron Features Identified in the Sloan Digital Sky Survey
Two newly identified magnetic cataclysmic variables discovered in the Sloan
Digital Sky Survey (SDSS), SDSSJ155331.12+551614.5 and SDSSJ132411.57+032050.5,
have spectra showing highly prominent, narrow, strongly polarized cyclotron
humps with amplitudes that vary on orbital periods of 4.39 and 2.6 hrs,
respectively. In the former, the spacing of the humps indicates the 3rd and 4th
harmonics in a magnetic field of ~60 MG. The narrowness of the cyclotron
features and the lack of strong emission lines imply very low temperature
plasmas and very low accretion rates, so that the accreting area is heated by
particle collisions rather than accretion shocks. The detection of rare systems
like these exemplifies the ability of the SDSS to find the lowest accretion
rate close binaries.Comment: Accepted for publication in the Astrophysical Journal, vol. 583,
February 1, 2003; slight revisions and additions in response to referee's
comments; 17 pages, 6 figures, AASTeX v4.
LSST Science Book, Version 2.0
A survey that can cover the sky in optical bands over wide fields to faint
magnitudes with a fast cadence will enable many of the exciting science
opportunities of the next decade. The Large Synoptic Survey Telescope (LSST)
will have an effective aperture of 6.7 meters and an imaging camera with field
of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over
20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with
fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a
total point-source depth of r~27.5. The LSST Science Book describes the basic
parameters of the LSST hardware, software, and observing plans. The book
discusses educational and outreach opportunities, then goes on to describe a
broad range of science that LSST will revolutionize: mapping the inner and
outer Solar System, stellar populations in the Milky Way and nearby galaxies,
the structure of the Milky Way disk and halo and other objects in the Local
Volume, transient and variable objects both at low and high redshift, and the
properties of normal and active galaxies at low and high redshift. It then
turns to far-field cosmological topics, exploring properties of supernovae to
z~1, strong and weak lensing, the large-scale distribution of galaxies and
baryon oscillations, and how these different probes may be combined to
constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at
http://www.lsst.org/lsst/sciboo
The Baryon Oscillation Spectroscopic Survey of SDSS-III
The Baryon Oscillation Spectroscopic Survey (BOSS) is designed to measure the
scale of baryon acoustic oscillations (BAO) in the clustering of matter over a
larger volume than the combined efforts of all previous spectroscopic surveys
of large scale structure. BOSS uses 1.5 million luminous galaxies as faint as
i=19.9 over 10,000 square degrees to measure BAO to redshifts z<0.7.
Observations of neutral hydrogen in the Lyman alpha forest in more than 150,000
quasar spectra (g<22) will constrain BAO over the redshift range 2.15<z<3.5.
Early results from BOSS include the first detection of the large-scale
three-dimensional clustering of the Lyman alpha forest and a strong detection
from the Data Release 9 data set of the BAO in the clustering of massive
galaxies at an effective redshift z = 0.57. We project that BOSS will yield
measurements of the angular diameter distance D_A to an accuracy of 1.0% at
redshifts z=0.3 and z=0.57 and measurements of H(z) to 1.8% and 1.7% at the
same redshifts. Forecasts for Lyman alpha forest constraints predict a
measurement of an overall dilation factor that scales the highly degenerate
D_A(z) and H^{-1}(z) parameters to an accuracy of 1.9% at z~2.5 when the survey
is complete. Here, we provide an overview of the selection of spectroscopic
targets, planning of observations, and analysis of data and data quality of
BOSS.Comment: 49 pages, 16 figures, accepted by A
Distinct Patterns of DNA Damage Response and Apoptosis Correlate with Jak/Stat and PI3Kinase Response Profiles in Human Acute Myelogenous Leukemia
BACKGROUND:Single cell network profiling (SCNP) utilizing flow cytometry measures alterations in intracellular signaling responses. Here SCNP was used to characterize Acute Myeloid Leukemia (AML) disease subtypes based on survival, DNA damage response and apoptosis pathways. METHODOLOGY AND PRINCIPAL FINDINGS:Thirty four diagnostic non-M3 AML samples from patients with known clinical outcome were treated with a panel of myeloid growth factors and cytokines, as well as with apoptosis-inducing agents. Analysis of induced Jak/Stat and PI3K pathway responses in blasts from individual patient samples identified subgroups with distinct signaling profiles that were not seen in the absence of a modulator. In vitro exposure of patient samples to etoposide, a DNA damaging agent, revealed three distinct "DNA damage response (DDR)/apoptosis" profiles: 1) AML blasts with a defective DDR and failure to undergo apoptosis; 2) AML blasts with proficient DDR and failure to undergo apoptosis; 3) AML blasts with proficiency in both DDR and apoptosis pathways. Notably, AML samples from clinical responders fell within the "DDR/apoptosis" proficient profile and, as well, had low PI3K and Jak/Stat signaling responses. In contrast, samples from clinical non responders had variable signaling profiles often with in vitro apoptotic failure and elevated PI3K pathway activity. Individual patient samples often harbored multiple, distinct, leukemia-associated cell populations identifiable by their surface marker expression, functional performance of signaling pathway in the face of cytokine or growth factor stimulation, as well as their response to apoptosis-inducing agents. CONCLUSIONS AND SIGNIFICANCE:Characterizing and tracking changes in intracellular pathway profiles in cell subpopulations both at baseline and under therapeutic pressure will likely have important clinical applications, potentially informing the selection of beneficial targeted agents, used either alone or in combination with chemotherapy
Set Pseudophasors to Stun for Flow Cytometry
Study of signal transduction in live cells benefits from the ability to visualize and quantify light emitted by fluorescent proteins (XFPs) fused to different signaling proteins. However, because cell signaling proteins are often present in small numbers, and because the XFPs themselves are poor fluorophores, the amount of emitted light, and the observable signal in these studies, is often small. An XFP's fluorescence lifetime contains additional information about the immediate environment of the fluorophore that can augment the information from its weak light signal. Here, we constructed and expressed in Saccharomyces cerevisiae variants of Teal Fluorescent Protein (TFP) and Citrine that were isospectral but had shorter fluorescence lifetimes, βΌ 1.5 ns vs βΌ 3 ns. We modified microscopic and flow cytometric instruments to measure fluorescence lifetimes in live cells. We developed digital hardware and a measure of lifetime called a "pseudophasor" that we could compute quickly enough to permit sorting by lifetime in flow. We used these abilities to sort mixtures of cells expressing TFP and the short-lifetime TFP variant into subpopulations that were respectively 97% and 94% pure. This work demonstrates the feasibility of using information about fluorescence lifetime to help quantify cell signaling in living cells at the high throughput provided by flow cytometry. Moreover, it demonstrates the feasibility of isolating and recovering subpopulations of cells with different XFP lifetimes for subsequent experimentation
Functional Characterization of FLT3 Receptor Signaling Deregulation in Acute Myeloid Leukemia by Single Cell Network Profiling (SCNP)
Molecular characterization of the FMS-like tyrosine kinase 3 receptor (FLT3) in cytogenetically normal acute myeloid leukemia (AML) has recently been incorporated into clinical guidelines based on correlations between FLT3 internal tandem duplications (FLT3-ITD) and decreased disease-free and overall survival. These mutations result in constitutive activation of FLT3, and FLT3 inhibitors are currently undergoing trials in AML patients selected on FLT3 molecular status. However, the transient and partial responses observed suggest that FLT3 mutational status alone does not provide complete information on FLT3 biological activity at the individual patient level. Examination of variation in cellular responsiveness to signaling modulation may be more informative.Using single cell network profiling (SCNP), cells were treated with extracellular modulators and their functional responses were quantified by multiparametric flow cytometry. Intracellular signaling responses were compared between healthy bone marrow myeloblasts (BMMb) and AML leukemic blasts characterized as FLT3 wild type (FLT3-WT) or FLT3-ITD. Compared to healthy BMMb, FLT3-WT leukemic blasts demonstrated a wide range of signaling responses to FLT3 ligand (FLT3L), including elevated and sustained PI3K and Ras/Raf/Erk signaling. Distinct signaling and apoptosis profiles were observed in FLT3-WT and FLT3-ITD AML samples, with more uniform signaling observed in FLT3-ITD AML samples. Specifically, increased basal p-Stat5 levels, decreased FLT3L induced activation of the PI3K and Ras/Raf/Erk pathways, decreased IL-27 induced activation of the Jak/Stat pathway, and heightened apoptotic responses to agents inducing DNA damage were observed in FLT3-ITD AML samples. Preliminary analysis correlating these findings with clinical outcomes suggests that classification of patient samples based on signaling profiles may more accurately reflect FLT3 signaling deregulation and provide additional information for disease characterization and management.These studies show the feasibility of SCNP to assess modulated intracellular signaling pathways and characterize the biology of individual AML samples in the context of genetic alterations
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