Description: Cortney M. Bouldin, Alyssa J. Manning, Yu-Hsuan Peng, Gist H. Farr III, King L. Hung, Alice Dong, and David Kimelman Anterior to posterior growth of the vertebrate body is fueled by a posteriorly located population of bipotential neuro-mesodermal progenitor cells. These progenitors have a limited rate of proliferation and their maintenance is crucial for completion of the anterior-posterior axis. How they leave the progenitor state and commit to differentiation is largely unknown, in part because widespread modulation of factors essential for this process causes organism-wide effects. Using a novel assay, we show that zebrafish Tbx16 (Spadetail) is capable of advancing mesodermal differentiation cell-autonomously. Tbx16 locks cells into the mesodermal state by not only activating downstream mesodermal genes, but also by repressing bipotential progenitor genes, in part through a direct repression of sox2 . We demonstrate that tbx16 is activated as cells move from an intermediate Wnt environment to a high Wnt environment, and show that Wnt signaling activates the tbx16 promoter. Importantly, high-level Wnt signaling is able to accelerate mesodermal differentiation cell-autonomously, just as we observe with Tbx16. Finally, because our assay for mesodermal commitment is quantitative we are able to show that the acceleration of mesodermal differentiation is surprisingly incomplete, implicating a potential separation of cell movement and differentiation during this process. Together, our data suggest a model in which high levels of Wnt signaling induce a transition to mesoderm by directly activating tbx16 , which in turn acts to irreversibly flip a bistable switch, leading to maintenance of the mesodermal fate and repression of the bipotential progenitor state, even as cells leave the initial high-Wnt environment.

Description: We develop a theory of minors for alternating dimaps—orientably embedded digraphs where, at each vertex, the incident edges (taken in the order given by the embedding) are directed alternately into, and out of, the vertex. We show that they are related by the triality relation of Tutte. They do not commute in general, though do in many circumstances, and we characterize the situations where they do. We give a characterization of alternating dimaps of at most a given genus, using a finite set of excluded minors. We also use the minor operations to define simple Tutte invariants for alternating dimaps and characterize them. We establish a connection with the Tutte polynomial, and pose the problem of characterizing universal Tutte-like invariants for alternating dimaps based on these minor operations.

Description: Optically stimulated luminescence (OSL) has been employed successfully to determine the ages of palaeosols from earthen mounds in the southeastern USA, providing archaeologists with a means of dating monument construction in the absence of carbonaceous materials and geologists with a setting for understanding factors that can affect the luminescence intensity (i.e., burial dose) of soils. However, OSL dating has not been adequately tested on mounds whose principal component is sand, shell, or a combination of these two, despite the fact that monuments composed of such materials are common to the coasts and interior coastal plains of the region. Radiocarbon dating of bone collagen and soil-carbon and OSL dating of quartz grains extracted from the fill of mounds at the Crystal River and Roberts Island sites on the west-central coast of Florida, USA are used to determine the timing and history of mound construction at the sites. Comparison of OSL and radiocarbon ages on materials from the same or closely related contexts provides insight into factors influencing age determinations in mound fill deposits, particularly the type of construction material (sand or shell) and the manner in which these were deposited. The results contribute to the understanding of the temporal context of platform mound construction in southeastern USA.

Description: We examine the performance of a variety of different estimators for the mass of galaxy groups, based on their galaxy distribution alone. We draw galaxies from the Sloan Digital Sky Survey for a set of groups and clusters for which hydrostatic mass estimates based on high-quality Chandra X-ray data are available. These are used to calibrate the galaxy-based mass proxies, and to test their performance. Richness, luminosity, galaxy overdensity, rms radius and dynamical mass proxies are all explored. These different mass indicators all have their merits, and we argue that using them in combination can provide protection against being misled by the effects of dynamical disturbance or variations in star formation efficiency. Using them in this way leads us to infer the presence of significant non-statistical scatter in the X-ray based mass estimates we employ. We apply a similar analysis to a set of mock groups derived from applying a semi-analytic galaxy formation code to the Millennium dark matter simulation. The relations between halo mass and the mass proxies differ significantly in some cases from those seen in the observational groups, and we discuss possible reasons for this.

Description: Background Stromal cell-derived factor-1 (SDF-1) promotes tissue repair through mechanisms of cell survival, endogenous stem cell recruitment, and vasculogenesis. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure (STOP-HF) is a Phase II, double-blind, randomized, placebo-controlled trial to evaluate safety and efficacy of a single treatment of plasmid stromal cell-derived factor-1 (pSDF-1) delivered via endomyocardial injection to patients with ischaemic heart failure (IHF). Methods Ninety-three subjects with IHF on stable guideline-based medical therapy and left ventricular ejection fraction (LVEF) ≤40%, completed Minnesota Living with Heart Failure Questionnaire (MLWHFQ) and 6-min walk distance (6 MWD), were randomized 1 : 1 : 1 to receive a single treatment of either a 15 or 30 mg dose of pSDF-1 or placebo via endomyocardial injections. Safety and efficacy parameters were assessed at 4 and 12 months after injection. Left ventricular functional and structural measures were assessed by contrast echocardiography and quantified by a blinded independent core laboratory. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure was powered based on change in 6 MWD and MLWHFQ at 4 months. Results Subject profiles at baseline were (mean ± SD): age 65 ± 9 years, LVEF 28 ± 7%, left ventricular end-systolic volume (LVESV) 167 ± 66 mL, N-terminal pro brain natriuretic peptide (BNP) (NTproBNP) 1120 ± 1084 pg/mL, MLWHFQ 50 ± 20 points, and 6 MWD 289 ± 99 m. Patients were 11 ± 9 years post most recent myocardial infarction. Study injections were delivered without serious adverse events in all subjects. Sixty-two patients received drug with no unanticipated serious product-related adverse events. The primary endpoint was a composite of change in 6 MWD and MLWHFQ from baseline to 4 months follow-up. The primary endpoint was not met ( P = 0.89). For the patients treated with pSDF-1, there was a trend toward an improvement in LVEF at 12 months (placebo vs. 15 mg vs. 30 mg LVEF: –2 vs. –0.5 vs. 1.5%, P = 0.20). A pre-specified analysis of the effects of pSDF-1 based on tertiles of LVEF at entry revealed improvements in EF and LVESV from lowest-to-highest LVEF. Patients in the first tertile of EF (〈26%) that received 30 mg of pSDF-1 demonstrated a 7% increase in EF compared with a 4% decrease in placebo (LVEF = 11%, P = 0.01) at 12 months. There was also a trend towards improvement in LVESV, with treated patients demonstrating an 18.5 mL decrease compared with a 15 mL increase for placebo at 12 months (LVESV = 33.5 mL, P = 0.12). The change in end-diastolic and end-systolic volume equated to a 14 mL increase in stroke volume in the patients treated with 30 mg of pSDF-1 compared with a decrease of –11 mL in the placebo group (SV = 25 mL, P = 0.09). In addition, the 30 mg-treated cohort exhibited a trend towards improvement in NTproBNP compared with placebo at 12 months (–784 pg/mL, P = 0.23). Conclusions The blinded placebo-controlled STOP-HF trial demonstrated the safety of a single endocardial administration of pSDF-1 but failed to demonstrate its primary endpoint of improved composite score at 4 months after treatment. Through a pre-specified analysis the STOP-HF trial demonstrates the potential for attenuating LV remodelling and improving EF in high-risk ischaemic cardiomyopathy. The safety profile supports repeat dosing with pSDF-1 and the degree of left ventricular remodelling suggests the potential for improved outcomes in larger future trials.

Description: This work demonstrates strong coupling regime between an erbium ion spin ensemble and microwave hybrid cavity-whispering gallery modes in a yttrium aluminium garnet dielectric crystal. Coupling strengths of 220 MHz and mode quality factors in excess of 10 6 are demonstrated. Moreover, the magnetic response of high-Q modes demonstrates behaviour which is unusual for paramagnetic systems. This behaviour includes hysteresis and memory effects. Such qualitative change of the system's magnetic field response is interpreted as a phase transition of rare earth ion impurities. This phenomenon is similar to the phenomenon of dilute ferromagnetism in semiconductors. The clear temperature dependence of the phenomenon is demonstrated.

Description: Drought struck California during 7 of the 9 years from 2007 through 2015, reducing the state's available water resources. Pumping of Central Valley groundwater has produced spectacular land subsidence. Uplift of the adjacent Sierra Nevada mountains has been proposed to be either tectonic uplift or solid Earth's elastic response to unloading of Central Valley groundwater. We find that, of the 24 mm of uplift of the Sierra Nevada from October 2011 to October 2015, just 5 mm is produced by Central Valley groundwater loss, less than 2 mm is tectonic uplift, and 17 mm is solid Earth's elastic response to water loss in the Sierra Nevada. We invert GPS vertical displacements recording solid Earth's elastic response to infer changes in water storage across the western U.S. from January 2006 to October 2017. We find water changes to be sustained over periods of drought or heavy precipitation: the Sierra Nevada lost 15 ±19 km 3 of water during drought from October 2006 to October 2009, gained 18 ±14 km 3 of water during heavy precipitation from October 2009 to October 2011, and lost 45 ±21 km 3 of water during severe drought from October 2011 to October 2015 (95% confidence limits). Such large changes are not in hydrology models: snow accumulation in October is negligible and long-term soil moisture change is small. We infer there must be large loss of either deep soil moisture or groundwater in river alluvium and in crystalline basement in the Sierra Nevada. The results suggest there to be parching of water in the ground during the summer of years of drought and seeping of melting snow into the Sierra Nevada in the spring of years of heavy precipitation.

Description: ABSTRACT The evasion of greenhouse gases (including CO 2 , CH 4 and N 2 O) from streams and rivers to the atmosphere is an important process in global biogeochemical cycles, but our understanding of gas transfer in steep (〉 10%) streams, and under varying flows is limited. We investigated gas transfer using combined tracer injections of SF 6 and salt. We used a novel experimental design in which we compared four very steep (18.4-29.4%) and four moderately steep (3.7-7.6%) streams, and conducted tests in each stream under low flow conditions and during a high discharge event. Most dissolved gas evaded over short distances (~100 and ~200-400 m respectively), so accurate estimates of evasion fluxes will require sampling of dissolved gases at these scales to account for local sources. We calculated CO 2 gas transfer coefficients ( K CO2 ) and found statistically significant differences between larger K CO2 values for steeper (mean 0.465 min -1 ) streams compared to those with shallower slopes (mean 0.109 min -1 ). Variations in flow had an even greater influence. K CO2 was substantially larger under high (mean 0.497 min -1 ) compared to low flow conditions (mean 0.077 min -1 ). We developed a statistical model to predict K CO2 using values of stream bed slope x discharge which accounted for 94 % of the variation. We show that two models using slope and velocity developed by Raymond et al. [2012] for streams and rivers with shallower slopes, also provide reasonable estimates of our CO 2 gas transfer velocities ( k CO2; m d -1 ). We developed a robust field protocol which could be applied in future studies.

Description: Author(s): Daniel L. Creedon, Jean-Michel Le Floch, Maxim Goryachev, Warrick G. Farr, Stefania Castelletto, and Michael E. Tobar We report strong coupling between an ensemble of N impurity ( P 1 ) centers in diamond and microwave photons using a unique double-post reentrant cavity. The cavity is designed so that the magnetic component of the cavity field is spatially separated from the electric component and focused into the sma... [Phys. Rev. B 91, 140408] Published Fri Apr 24, 2015

Description: Interaction of Whispering Gallery Modes (WGMs) with dilute spin ensembles in solids is an interesting paradigm of Hybrid Quantum Systems potentially beneficial for Quantum Signal Processing applications. Unexpected ion transitions are measured in single crystal Y 2 SiO 5 using WGM spectroscopy with large Zero Field Splittings at 14.7 GHz, 18.4 GHz, and 25.4 GHz, which also feature considerable anisotropy of the g-tensors as well as two inequivalent lattice sites, indicating spins from Iron Group Ion (IGI) impurities. The comparison of undoped and Rare-Earth doped crystals reveal that the IGIs are introduced during co-doping of Eu 3+ or Er 3+ with concentration at much lower levels of order 100 ppb. The strong coupling regime between an ensemble of IGI spins and WGM photons have been demonstrated at 18.4 GHz and near zero field. This approach together with useful optical properties of these ions opens avenues for “spins-in-solids” Quantum Electrodynamics.