Reversible Optogenetic Control of Subcellular Protein Localization in a Live Vertebrate Embryo.

We demonstrate the utility of the phytochrome system to rapidly and reversibly recruit proteins to specific subcellular regions within specific cells in a living vertebrate embryo. Light-induced heterodimerization using the phytochrome system has previously been used as a powerful tool to dissect signaling pathways for single cells in culture but has not previously been used to reversibly manipulate the precise subcellular location of proteins in multicellular organisms. Here we report the experimental conditions necessary to use this system to manipulate proteins in vivo. As proof of principle, we demonstrate that we can manipulate the localization of the apical polarity protein Pard3 with high temporal and spatial precision in both the neural tube and the embryo's enveloping layer epithelium. Our optimizations of optogenetic component expression and chromophore purification and delivery should significantly lower the barrier for establishing this powerful optogenetic system in other multicellular organisms

Andromeda's Parachute: A Bright Quadruply Lensed Quasar at z=2.377

We present Keck Cosmic Web Imager spectroscopy of the four putative images of the lensed quasar candidate J014709+463037 recently discovered by Berghea et al. (2017). The data verify the source as a quadruply lensed, broad absorption-line quasar having z_S = 2.377 +/- 0.007. We detect intervening absorption in the FeII 2586, 2600, MgII 2796, 2803, and/or CIV 1548, 1550 transitions in eight foreground systems, three of which have redshifts consistent with the photometric-redshift estimate reported for the lensing galaxy (z_L ~ 0.57). By virtue of their positions on the sky, the source images probe these absorbers over transverse physical scales of ~0.3-21 kpc, permitting assessment of the variation in metal-line equivalent width W_r as a function of sight-line separation. We measure differences in W_r,2796 of <40% across all sight-line pairs subtending 7-21 kpc, suggestive of a high degree of spatial coherence for MgII-absorbing material. W_r,2600 is observed to vary by >50% over the same scales across the majority of sight-line pairs, while CIV absorption exhibits a wide range in W_r,1548 differences of ~5-80% within transverse distances less than ~3 kpc. J014709+463037 is one of only a handful of z > 2 quadruply lensed systems for which all four source images are very bright (r = 15.4-17.7 mag) and are easily separated in ground-based seeing conditions. As such, it is an ideal candidate for higher-resolution spectroscopy probing the spatial variation in the kinematic structure and physical state of intervening absorbers.Comment: Submitted to ApJL. 9 pages, 3 figures. Uses aastex61 forma

The infrared imaging spectrograph (IRIS) for TMT: the science case

The InfraRed Imaging Spectrograph (IRIS) is a first-light instrument being designed for the Thirty Meter Telescope (TMT). IRIS is a combination of an imager that will cover a 16.4" field of view at the diffraction limit of TMT (4 mas sampling), and an integral field unit spectrograph that will sample objects at 4-50 mas scales. IRIS will open up new areas of observational parameter space, allowing major progress in diverse fields of astronomy. We present the science case and resulting requirements for the performance of IRIS. Ultimately, the spectrograph will enable very well-resolved and sensitive studies of the kinematics and internal chemical abundances of high-redshift galaxies, shedding light on many scenarios for the evolution of galaxies at early times. With unprecedented imaging and spectroscopy of exoplanets, IRIS will allow detailed exploration of a range of planetary systems that are inaccessible with current technology. By revealing details about resolved stellar populations in nearby galaxies, it will directly probe the formation of systems like our own Milky Way. Because it will be possible to directly characterize the stellar initial mass function in many environments and in galaxies outside of the the Milky Way, IRIS will enable a greater understanding of whether stars form differently in diverse conditions. IRIS will reveal detailed kinematics in the centers of low-mass galaxies, allowing a test of black hole formation scenarios. Finally, it will revolutionize the characterization of reionization and the first galaxies to form in the universe.Comment: to appear in Proc. SPIE 773

The Decade of the Dendritic NMDA Spike

In the field of cortical cellular physiology, much effort has been invested in understanding thick apical drites of pyramidal neurons and the regenerative sodium and calcium spikes that take place in the apical trunk. Here we focus on thin dendrites of pyramidal cells (basal, oblique, and tuft dendrites), and we discuss one relatively novel form of an electrical signal (“NMDA spike”) that is specific for these branches. Basal, oblique, and apical tuft dendrites receive a high density of glutamatergic synaptic contacts. Synchronous activation of 10–50 neighboring glutamatergic synapses triggers a local dendritic regenerative potential, NMDA spike/plateau, which is characterized by significant local amplitude (40–50 mV) and an extraordinary duration (up to several hundred milliseconds). The NMDA plateau potential, when it is initiated in an apical tuft dendrite, is able to maintain a good portion of that tuft in a sustained depolarized state. However, if NMDA-dominated plateau potentials originate in proximal segments of basal dendrites, they regularly bring the neuronal cell body into a sustained depolarized state, which resembles a cortical up state. At each dendritic initiation site (basal, oblique, and tuft) an NMDA spike creates favorable conditions for causal interactions of active synaptic inputs, including the spatial or temporal binding of information, as well as processes of short-term and long-term synaptic modifications (e.g., long-term potentiation or long-term depression). Because of their strong amplitudes and durations, local dendritic NMDA spikes make up the cellular substrate for multisite independent subunit computations that enrich the computational power and repertoire of cortical pyramidal cells. We propose that NMDA spikes are likely to play significant roles in cortical information processing in awake animals (spatiotemporal binding, working memory) and during slow-wave sleep (neuronal up states, consolidation of memories

First-order flow equations for extremal black holes in very special geometry

We construct interpolating solutions describing single-center static extremal non-supersymmetric black holes in four-dimensional N=2 supergravity theories with cubic prepotentials. To this end, we derive and solve first-order flow equations for rotating electrically charged extremal black holes in a Taub-NUT geometry in five dimensions. We then use the connection between five- and four-dimensional extremal black holes to obtain four-dimensional flow equations and we give the corresponding solutions.Comment: 21 pages. v2: Summary section adde

Robust Ecosystem Demography (RED version 1.0): a parsimonious approach to modelling vegetation dynamics in Earth system models

A significant proportion of the uncertainty in climate projections arises from uncertainty in the representation of land carbon uptake. Dynamic global vegetation models (DGVMs) vary in their representations of regrowth and competition for resources, which results in differing responses to changes in atmospheric CO2 and climate. More advanced cohort-based patch models are now becoming established in the latest DGVMs. These models typically attempt to simulate the size distribution of trees as a function of both tree size (mass or trunk diameter) and age (time since disturbance). This approach can capture the overall impact of stochastic disturbance events on the forest structure and biomass – but at the cost of increasing the number of parameters and ambiguity when updating the probability density function (pdf) in two dimensions. Here we present the Robust Ecosystem Demography (RED), in which the pdf is collapsed onto the single dimension of tree mass. RED is designed to retain the ability of more complex cohort DGVMs to represent forest demography, while also being parameter sparse and analytically solvable for the steady state. The population of each plant functional type (PFT) is partitioned into mass classes with a fixed baseline mortality along with an assumed power-law scaling of growth rate with mass. The analytical equilibrium solutions of RED allow the model to be calibrated against observed forest cover using a single parameter – the ratio of mortality to growth for a tree of a reference mass (μ0). We show that RED can thus be calibrated to the ESA LC_CCI (European Space Agency Land Cover Climate Change Initiative) coverage dataset for nine PFTs. Using net primary productivity and litter outputs from the UK Earth System Model (UKESM), we are able to diagnose the spatially varying disturbance rates consistent with this observed vegetation map. The analytical form for RED circumnavigates the need to spin up the numerical model, making it attractive for application in Earth system models (ESMs). This is especially so given that the model is also highly parameter sparse

Investigating spillover of multidrug-resistant tuberculosis from a prison: a spatial and molecular epidemiological analysis.

BACKGROUND: Congregate settings may serve as institutional amplifiers of tuberculosis (TB) and multidrug-resistant tuberculosis (MDR-TB). We analyze spatial, epidemiological, and pathogen genetic data prospectively collected from neighborhoods surrounding a prison in Lima, Peru, where inmates experience a high risk of MDR-TB, to investigate the risk of spillover into the surrounding community. METHODS: Using hierarchical Bayesian statistical modeling, we address three questions regarding the MDR-TB risk: (i) Does the excess risk observed among prisoners also extend outside the prison? (ii) If so, what is the magnitude, shape, and spatial range of this spillover effect? (iii) Is there evidence of additional transmission across the region? RESULTS: The region of spillover risk extends for 5.47 km outside of the prison (95% credible interval: 1.38, 9.63 km). Within this spillover region, we find that nine of the 467 non-inmate patients (35 with MDR-TB) have MDR-TB strains that are genetic matches to strains collected from current inmates with MDR-TB, compared to seven out of 1080 patients (89 with MDR-TB) outside the spillover region (p values: 0.022 and 0.008). We also identify eight spatially aggregated genetic clusters of MDR-TB, four within the spillover region, consistent with local transmission among individuals living close to the prison. CONCLUSIONS: We demonstrate a clear prison spillover effect in this population, which suggests that interventions in the prison may have benefits that extend to the surrounding community

Provider Counseling, Health Education, and Community Health Workers: The Arizona WISEWOMAN Project

Background: The Arizona Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) project used provider counseling, health education, and community health workers (CHWs) to target chronic disease risk factors in uninsured, primarily Hispanic women over age 50. Methods: Participants were recruited from two Tucson clinics participating in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Women were randomly assigned into one of three intervention groups: (1) provider counseling, (2) provider counseling and health education, or (3) provider counseling, health education, and CHW support. At baseline and 12 months (1998–2000), participants were measured for height, weight, waist and hip circumference, and blood pressure. Blood tests were conducted to check blood glucose, cholesterol, and triglyceride levels. At each time point, participants also completed 24-hour dietary recalls and questionnaires focusing on their physical activity levels. Results: A total of 217 women participated in baseline and 12-month follow-up. Three fourths were Hispanic. All three intervention groups showed an increase in self-reported weekly minutes of moderate-to-vigorous physical activity, with no significant differences between the groups. Significantly more women who received the comprehensive intervention of provider counseling, health education, and CHW support progressed to eating five fruits and vegetables per day, compared with participants who received only provider counseling or provider counseling plus health education. Conclusions: All three interventions increased moderate-to-vigorous physical activity but not fruit and vegetable consumption. The intervention group with provider counseling, health education, and CHW support significantly increased the number of women meeting national recommendations for fruit and vegetable consumption

A Close Companion Search Around L Dwarfs Using Aperture Masking Interferometry and Palomar Laser Guide Star Adaptive Optics

We present a close companion search around 16 known early L dwarfs using aperture masking interferometry with Palomar laser guide star adaptive optics (LGS AO). The use of aperture masking allows the detection of close binaries, corresponding to projected physical separations of 0.6-10.0 AU for the targets of our survey. This survey achieved median contrast limits of ΔK ~ 2.3 for separations between 1.2λ/D-4λ/D and ΔK ~ 1.4 at 2/3λ/D. We present four candidate binaries detected with moderate-to-high confidence (90%-98%). Two have projected physical separations less than 1.5 AU. This may indicate that tight-separation binaries contribute more significantly to the binary fraction than currently assumed, consistent with spectroscopic and photometric overluminosity studies. Ten targets of this survey have previously been observed with the Hubble Space Telescope as part of companion searches. We use the increased resolution of aperture masking to search for close or dim companions that would be obscured by full aperture imaging, finding two candidate binaries. This survey is the first application of aperture masking with LGS AO at Palomar. Several new techniques for the analysis of aperture masking data in the low signal-to-noise regime are explored