We present Hubble Space Telescope Wide Field Camera 3 photometric and grism observations of the candidate ultra-high-redshift ($z>7$) radio galaxy, GLEAM J0917–0012. This radio source was selected due to the curvature in its 70–230 MHz, low-frequency Murchison Widefield Array radio spectrum and its faintness in K-band. Follow-up spectroscopic observations of this source with the Jansky Very Large Array and Atacama Large Millimetre Array were inconclusive as to its redshift. Our F105W and F0986M imaging observations detect the host of GLEAM J0917–0012 and a companion galaxy, $\sim$ one arcsec away. The G102 grism observations reveal a single weak line in each of the spectra of the host and the companion. To help identify these lines we utilised several photometric redshift techniques including template fitting to the grism spectra, fitting the ultraviolet (UV)-to-radio photometry with galaxy templates plus a synchrotron model, fitting of the UV-to-near-infrared photometry with EAZY, and fitting the radio data alone with RAiSERed. For the host of GLEAM J0917–0012 we find a line at $1.12\,\mu$m and the UV-to-radio spectral energy distribution (SED) fitting favours solutions at $z\sim 2$ or $z\sim 8$. While this fitting shows a weak preference for the lower redshift solution, the models from the higher redshift solution are more consistent with the strength of the spectral line. The redshift constraint by RAiSERed of $>6.5$ also supports the interpretation that this line could be Lyman$-\alpha$ at $z=8.21$; however EAZY favours the $z\sim 2$ solution. We discuss the implications of both solutions. For the companion galaxy we find a line at $0.98\,\mu$m and the SED fitting favours solutions at $z<3$ implying that the line could be the [OII]$\lambda3727$ doublet at $z=1.63$ (although the EAZY solution is $z\sim 2.6\pm 0.5$). Further observations are still required to unambiguously determine the redshift of this intriguing candidate ultra-high-redshift radio galaxy.

We present an overview of the Middle Ages Galaxy Properties with Integral Field Spectroscopy (MAGPI) survey, a Large Program on the European Southern Observatory Very Large Telescope. MAGPI is designed to study the physical drivers of galaxy transformation at a lookback time of 3–4 Gyr, during which the dynamical, morphological, and chemical properties of galaxies are predicted to evolve significantly. The survey uses new medium-deep adaptive optics aided Multi-Unit Spectroscopic Explorer (MUSE) observations of fields selected from the Galaxy and Mass Assembly (GAMA) survey, providing a wealth of publicly available ancillary multi-wavelength data. With these data, MAGPI will map the kinematic and chemical properties of stars and ionised gas for a sample of 60 massive (${>}7 \times 10^{10} {\mathrm{M}}_\odot$) central galaxies at $0.25 < z <0.35$ in a representative range of environments (isolated, groups and clusters). The spatial resolution delivered by MUSE with Ground Layer Adaptive Optics ($0.6-0.8$ arcsec FWHM) will facilitate a direct comparison with Integral Field Spectroscopy surveys of the nearby Universe, such as SAMI and MaNGA, and at higher redshifts using adaptive optics, for example, SINS. In addition to the primary (central) galaxy sample, MAGPI will deliver resolved and unresolved spectra for as many as 150 satellite galaxies at $0.25 < z <0.35$, as well as hundreds of emission-line sources at $z < 6$. This paper outlines the science goals, survey design, and observing strategy of MAGPI. We also present a first look at the MAGPI data, and the theoretical framework to which MAGPI data will be compared using the current generation of cosmological hydrodynamical simulations including EAGLE, Magneticum, HORIZON-AGN, and Illustris-TNG. Our results show that cosmological hydrodynamical simulations make discrepant predictions in the spatially resolved properties of galaxies at $z\approx 0.3$. MAGPI observations will place new constraints and allow for tangible improvements in galaxy formation theory.

We present an analytical study of two-dimensional flow in a wedge driven by a time-dependent surface heat flux as a model problem to understand buoyancy-induced cross-shore flow. Besides the turbulent Prandtl number and the relevant Rayleigh number, both assumed to be of order unity, the solution is seen to depend on the geometry through a parameter $\beta$, representing the bottom slope. An analytic solution is sought in the asymptotic limit $\beta \ll 1$ for a water layer bounded by an adiabatic bottom surface subject to a harmonic heat flux on the upper surface. The analysis reveals that the motion at leading order can be expressed as the sum of a harmonic component and a steady component, the latter driven by nonlinear advection. This steady-streaming motion includes a near-shore vortex with associated recirculating motion that can affect cross-shore transport and dispersion in coastal environments. The analytical solution is compared with numerical solutions of the complete conservation equations for small values of $\beta$. Excellent quantitative agreement is found for values of the Rayleigh number below a critical value at which the periodic solution undergoes a period-doubling bifurcation, leading to the establishment of thermal-instability cells that dominate the offshore flow dynamics, while the near-shore dynamics remains well described by the analytical solution. The analysis illustrates that a periodic heat input that leads to a vertically inhomogeneous temperature distribution can result in residual motion, net heat fluxes and persistent temperature structure in the cross-shore direction.

Maternal nutrition is critical in mammalian development, influencing the epigenetic reprogramming of gametes, embryos, and fetal programming. We evaluated the effects of different levels of sulfur (S) and cobalt (Co) in the maternal diet throughout the pre- and periconceptional periods on the biochemical and reproductive parameters of the donors and the DNA methylome of the progeny in Bos indicus cattle. The low-S/Co group differed from the control with respect to homocysteine, folic acid, B12, insulin growth factor 1, and glucose. The oocyte yield was lower in heifers from the low S/Co group than that in the control heifers. Embryos from the low-S/Co group exhibited 2320 differentially methylated regions (DMRs) across the genome compared with the control embryos. We also characterized candidate DMRs linked to the DNMT1 and DNMT3B genes in the blood and sperm cells of the adult progeny. A DMR located in DNMT1 that was identified in embryos remained differentially methylated in the sperm of the progeny from the low-S/Co group. Therefore, we associated changes in specific compounds in the maternal diet with DNA methylation modifications in the progeny. Our results help to elucidate the impact of maternal nutrition on epigenetic reprogramming in livestock, opening new avenues of research to study the effect of disturbed epigenetic patterns in early life on health and fertility in adulthood. Considering that cattle are physiologically similar to humans with respect to gestational length, our study may serve as a model for studies related to the developmental origin of health and disease in humans.

ABSTRACT IMPACT: Melanoma leptomeningeal disease (LMD) is a devastating subtype of central nervous system (CNS) metastatic disease that is associated with limited treatment options and an extremely poor prognosis, thus requiring the development of preclinical models of LMD for therapeutic development. OBJECTIVES/GOALS:

1. 1. Develop an immunocompetent murine model of melanoma LMD with tumors bearing genetic mutations commonly found in patients, specifically BRAF(V600E)/PTEN-/-

2. 2. Assess the safety of intrathecal (IT) immunotherapy, specifically anti-PD1 antibody (aPD1)

3. 3. Evaluate the therapeutic efficacy of IT aPD1 checkpoint blockade in murine melanoma LMD METHODS/STUDY POPULATION: To develop BRAF(V600E)/PTEN-/- LMD models, we acquired BP, D4M, and D4M-UV2 (irradiated) murine melanoma cell lines and luciferase-tagged them. 1.5x10^4 cells were suspended in 10 uL serum-free media and injected into the cisterna magna of female C57BL/6 mice. Brain and spinal cord were harvested for histologic assessment once mice were moribund. To assess safety of IT aPD1, we injected IT control IgG or IT aPD1 (13 ug, 26 ug, 39 ug) and monitored weights or harvested at days 7 or 14 for IHC staining of inflammation markers. To evaluate therapeutic efficacy of IT aPD1, BP cells were directly injected as above. After 3 days, mice underwent imaging to confirm tumor uptake and randomization to receive 13 ug IT control IgG or aPD1 once + 200 ug systemic (Sys) control IgG or aPD1 (days 0, 3, and 5), and then monitored for survival. RESULTS/ANTICIPATED RESULTS: For LMD development, all mice survived cisternal injection of BP, D4M, and D4M-UV2 cells and median survival was 17, 19, and 30 days, respectively. Presence of leptomeningeal deposits was confirmed for all tumor-bearing mice by IHC for MART1. For safety of IT aPD1, all mice survived the procedure and no mice displayed morbidity or >10% weight loss over 14 days of observation. IHC assessment of brain and spinal cord samples from mice treated with 13 ug aPD1 revealed focal ischemia related to injection site and no other signs of neurological damage or inflammation. IT aPD1 treatment of mice with BP leptomeningeal tumors demonstrated no significant survival advantage, although both IT aPD1 +/- Sys aPD1 had mice live up to days 29 and 26, respectively, compared to both IT control IgG +/- Sys aPD1, for which all mice died by day 22. DISCUSSION/SIGNIFICANCE OF FINDINGS: We demonstrate that cisternal injection of murine BRAF(V600E)/PTEN-/- melanoma cell lines yield LMD with reproducible survival and that treatment with IT aPD1 in this model is feasible and safe. Together these findings establish a new model to facilitate the development of more effective immunotherapy strategies for melanoma patients with LMD.

The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case–control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014–February 2016. Case-patients were defined as children aged 1–5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18–17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.

The development of laser wakefield accelerators (LWFA) over the past several years has led to an interest in very compact sources of X-ray radiation – such as “table-top” free electron lasers. However, the use of conventional undulators using permanent magnets also implies system sizes which are large. In this work, we assess the possibilities for the use of novel mini-undulators in conjunction with a LWFA so that the dimensions of the undulator become comparable with the acceleration distances for LWFA experiments (i.e., centimeters). The use of a prototype undulator using laser machining of permanent magnets for this application is described and the emission characteristics and limitations of such a system are determined. Preliminary electron propagation and X-ray emission measurements are taken with a LWFA electron beam at the University of Michigan.

The type specimen of liskeardite, (Al, Fe)3AsO4(OH)6·5H2O, from the Marke Valley Mine, Liskeard District, Cornwall, has been reinvestigated. The revised composition from electron microprobe analyses and structure refinement is [Al29.2Fe2.8(AsO4)18(OH)42(H2O)22]·52H2O.The crystal structure was determined using synchrotron data collected on a 2 μm diameter fibre at 100 K. Liskeardite has monoclinic symmetry, space group I2, with the unit-cell parameters a = 24.576(5), b = 7.754(2) Å, c = 24.641(5) Å, and β= 90.19(1)º. The structure was refined to R = 0.059 for 9769 reflections with I > 3σ(I). It is of an open framework type in which intersecting polyhedral slabs parallel to (101) and (10) form 17.4 Å × 17.4 Å channels along [010], with watermolecules occupying the channels. Small amounts (<1 wt.%) of Na, K and Cu are probably adsorbed at the channel walls The framework comprises columns of pharmacoalumite-type, intergrown with chiral chains of six cis edge-shared octahedra. It can be described in terms of cubic closepacking, with vacancies at both the anion and cation sites. The compositional and structural relationships between liskeardite and pharmacoalumite are discussed and a possible mechanism for liskeardite formation is presented.

Yttrotungstite occurs at Kramat Pulai mine, and at Tapah, Kinta, Perak, Malaysia, as yellow earthy material and as monoclinic laths, elongated along [001], flattened, and always twinned, on {100} to pseudo-orthorhombic symmetry, and frequently bevelled by {110}; crystals are very rarely terminated by {101}. γ = [010], α:[001] = 26°, probably in β acute, and 2Vα ≃ 68°. A thermal weight loss curve and an infra-red absorption spectrum are given and discussed. Accessory minerals include raspite and stolzite.

The yttrotungstite unit cell has a 6·95, b 8·64, c 5·77, β 104° 56′, space group P21/m; cell contents are (Yt, Ln, Ca, Mg)2(W, Al, Si, Ti, Fe)4(O, OH)14(OH)2·2H2O. Indexed X-ray powder data are given. Microprobe studies show that Al and Si replace W and are concentrated in zones showing larger values of a sin β (6·75 Å instead of 6·72 Å) but with no other appreciable difference in cell dimensions. Crystal structure studies show that the structure consists of WO6 octahedra sharing non-opposite edges in zig-zag chains running parallel to [010]. Yttrium is in approximately trigonal prismatic coordination between the chains, with the water molecule as a seventh neighbour at one prism face. The water molecule is accommodated in the angle between zig-zags in the WO6 chains; it is probably hydrogen bonded to chain oxygen atoms, and becomes coordinated to the yttrium by a shear between chains away from strict close-packing of the oxygen atoms. The shear is related to the change in a sin β in (Al, Si)-rich zones; arguments based on this and on details of the chemical analysis suggest that SiO4 replaces WO6 with a local oxygen deficit.

Oxygen atom peaks on partial Fourier difference syntheses for our data for yttrotungstite are only slightly larger than the troughs in the syntheses due to experimental error. Methods of testing the significance of the positive peaks are described in an appendix.

The properties of the acoustic modes are sensitive to magnetic activity. The unprecedented long-term Kepler photometry, thus, allows stellar magnetic cycles to be studied through asteroseismology. We search for signatures of magnetic cycles in the seismic data of Kepler solar-type stars. We find evidence for periodic variations in the acoustic properties of about half of the 87 analysed stars. In these proceedings, we highlight the results obtained for two such stars, namely KIC 8006161 and KIC 5184732.

We report the breeding success of four species of burrow-nesting petrels at sub-Antarctic Marion Island where house mice Mus musculus are the sole introduced mammal. Feral cats Felis catus were present on Marion for four decades from 1949, killing millions of seabirds and greatly reducing petrel populations. Cats were eradicated by 1991, but petrel populations have shown only marginal recoveries. We hypothesize that mice are suppressing their recovery through depredation of petrel eggs and chicks. Breeding success for winter breeders (grey petrels Procellaria cinerea (34±21%) and great-winged petrels Pterodroma macroptera (52±7%)) were lower than for summer breeders (blue petrels Halobaena caerulea (61±6%) and white-chinned petrels Procellaria aequinoctialis (59±6%)) and among winter breeders most chick fatalities were of small chicks up to 14 days old. We assessed the extent of mouse predation by monitoring the inside of 55 burrow chambers with video surveillance cameras (4024 film days from 2012–16) and recorded fatal attacks on grey (3/18 nests filmed, 17%) and great-winged petrel chicks (1/19, 5%). Our results show that burrow-nesting petrels are at risk from mouse predation, providing further motivation for the eradication of mice from Marion Island.

We studied the uptake and transport of 4-amino-3,5,6-trichloropicolinic acid (picloram) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) alone and in combination and in the presence of 1,1′-dimethyl-4,4′-bipyridinium salt (paraquat) by honey mesquite (Prosopis juliflora (Swartz) DC. var. glandulosa (Torr.) Cockerell), huisache (Acacia farnesiana L. Willd., yaupon (Ilex vomitoria Ait.), and bean (Phaseolus vulgaris L.). Paraquat reduced transport of picloram by mesquite, huisache, and bean. Paraquat increased uptake of picloram by yaupon but did not affect transport. The uptake and transport of 2,4,5-T by mesquite decreased in the presence of picloram, but the uptake and transport of picloram increased in the presence of 2,4,5-T. Increasing ratios of 2,4,5-T:picloram up to 16:1 continued to increased uptake and transport of picloram; the inverse effect occurred for 2,4,5-T when picloram:2,4,5-T ratios were increased.

In western North America, the Western Stemmed Tradition (WST) is contemporaneous with, but technologically different from, the Clovis Paleoindian Tradition as initially defined from the Great Plains and American Southwest. The foundational principles of WST lithic technology have not been as clearly delineated as those of their fluted and unfluted Paleoindian Tradition technological counterparts, largely due to the paucity of extensive WST lithic assemblages recovered from intact buried contexts. Recent excavations at the Cooper's Ferry site, located in western Idaho, revealed a stratified series of WST components spanning the late Pleistocene to early Holocene periods. The study of these components offers a unique opportunity to evaluate current expectations about WST lithic technology. Here, we describe the discovery, context, and contents of a new cache of 14 WST projectile points from the Cooper's Ferry site that provide clues about WST lithic reduction patterns and the design of early stemmed projectile points. We employ several novel methods of lithic analysis based on three-dimensional digital scanning technology and geometric morphometry and, in doing so, seek to demonstrate new ways of studying stone tools through the use of next-generation methods of lithic analysis applied to exploring the poorly known technological details of the WST.

We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38–17·40), prior MRSA infection (OR 3·59; 95% CI 1·05–12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7–159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08–0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.

A field study was conducted in 2014 and 2015 in Arkansas, Illinois, Indiana, Ohio, Tennessee, Wisconsin, and Missouri to determine the effects of tillage system and herbicide program on season-long emergence of Amaranthus species in glufosinate-resistant soybean. The tillage systems evaluated were deep tillage (fall moldboard plow followed by (fb) one pass with a field cultivator in the spring), conventional tillage (fall chisel plow fb one pass with a field cultivator in the spring), minimum tillage (one pass of a vertical tillage tool in the spring), and no-tillage (PRE application of paraquat). Each tillage system also received one of two herbicide programs; PRE application of flumioxazin (0.09 kg ai ha–1) fb a POST application of glufosinate (0.59 kg ai ha−1) plus S-metolachlor (1.39 kg ai ha–1), or POST-only applications of glufosinate (0.59 kg ha−1). The deep tillage system resulted in a 62, 67, and 73% reduction in Amaranthus emergence when compared to the conventional, minimum, and no-tillage systems, respectively. The residual herbicide program also resulted in an 87% reduction in Amaranthus species emergence compared to the POST-only program. The deep tillage system, combined with the residual program, resulted in a 97% reduction in Amaranthus species emergence when compared to the minimum tillage system combined with the POST-only program, which had the highest Amaranthus emergence. Soil cores taken prior to planting and herbicide application revealed that only 28% of the Amaranthus seed in the deep tillage system was placed within the top 5-cm of the soil profile compared to 79, 81, and 77% in the conventional, minimum, and no-tillage systems. Overall, the use of deep tillage with a residual herbicide program provided the greatest reduction in Amaranthus species emergence, thus providing a useful tool in managing herbicide-resistant Amaranthus species where appropriate.