The MUSE view of the planetary nebula NGC 3132

ABRIDGED: 2D spectroscopic MUSE data for the whole extent of NGC3132 have been reduced and analised. The dust extinction, electron densities and temperatures of the ionised gas and abundances were determined. The nebula presents a complex reddening structure with high values (c(Hb)~0.4) at the rim. Density maps are compatible with an inner high-ionisation plasma at moderate high density (~1000cm^-3) while the low-ionisation plasma presents a structure in density peaking at the rim with values ~700 cm^-3. Median Te using different diagnostics decreases according to the sequence [NII],[SII]->[SIII]->[OI]->HeI->PJ. Likewise the range of Te covered by recombination lines is much larger than those obtained from CELs, with large spatial variations within the nebula. If these differences were due to the existence of high density clumps, these spatial variations suggest changes in the properties and/or distribution of the clumps within the nebula. We determined a median He/H=0.124. The range of measured ionic abundances for light elements are compatible with literature values. Our kinematic analysis nicely illustrates the power of 2D kinematic information in many emission lines to shed light on the intrinsic structure of the nebula. Our derived velocity maps support a geometry for the nebula similar to the previously propose diabolo model, but oriented with its major axis at P.A.~-22^o. We identified two low-surface brightness arc-like structures towards the northern and southern tips of the nebula, with high extinction, high helium abundance, and strong low-ionisation emission lines. They are spatially coincident with some extended low-surface brightness mid-IR emission. The characteristics of the features are compatible with being the consequence of precessing jets caused by the binary star system. This study illustrates the enormous potential of IFS for the study of Galactic PNe.Comment: 21 pages, 15 figures, 6 tables; accepted by A&

A one-year experimental Arctic reanalysis and comparisons with ERA-40 and NCEP/NCAR reanalyses.

[1] A one-year (1998) experimental Arctic reanalysis was produced using an experimental Arctic reanalysis system (EARS), which was based on the MM5 model and 3DVAR data assimilation, implemented in combination with an intermittent nudging scheme. TOVS retrieval data and conventional surface observations and upper-air sounding data are assimilated by EARS, which is driven by the ERA-40 reanalysis. The domain covers a pan-Arctic region at a horizontal resolution of 30 km. The EARS reanalysis results, as well as ERA-40 and NCEP/NCAR reanalyses (NNRP), are verified against station observations. Comparisons show that the ERA-40 analysis is significantly better than NNRP for the metrics of rootmean-square error and bias. The EARS performed significantly better than both ERA-40 and NNRP at lower levels; it produced especially good results for surface wind and upper-air humidity. For the surface temperature, dew point, relative humidity, sea level pressure, as well as upperair variables, the yearly average of the EARS results lie in between those of the ERA-40 and NNRP, closer to those of ERA-40. Citation: Fan, X., J. E. Walsh, and J. R. Kriege

Secreted metabolome of porcine blastocysts encapsulated with in \u3ci\u3ein vitro\u3c/i\u3e 3D alginate hydrogel culture systems under going morphological changes provides insights into specific mechanisms involved in the initiation of porcine conceptus elongation

Context. The exact mechanisms regulating the initiation of porcine conceptus elongation are not known due to the complexity of the uterine environment. Aims. To identify contributing factors for initiation of conceptus elongation in vitro, this study evaluated differential metabolite abundance within media following culture of blastocysts within unmodified alginate (ALG) or Arg-Gly-Asp (RGD)-modified alginate hydrogel culture systems. Methods. Blastocysts were harvested from pregnant gilts, encapsulated within ALG or RGD or as non-encapsulated control blastocysts (CONT), and cultured. At the termination of 96 h culture, media were separated into blastocyst media groups: non-encapsulated control blastocysts (CONT); ALG and RGD blastocysts with no morphological change (ALG− and RGD−); ALG and RGD blastocysts with morphological changes (ALG+ and RGD+) and evaluated for non-targeted metabolomic profiling by liquid chromatography (LC)–mass spectrometry (MS) techniques and gas chromatography– (GC–MS). Key results. Analysis of variance identified 280 (LC–MS) and 1 (GC–MS) compounds that differed (P \u3c 0.05), of which 134 (LC–MS) and 1 (GC–MS) were annotated. Metabolites abundance between ALG+ vs ALG−, RGD+ vs RGD−, and RGD+ vs ALG+ were further investigated to identify potential differences in metabolic processes during the initiation of elongation. Conclusions. This study identified changes in phospholipid, glycosphingolipid, lipid signalling, and amino acid metabolic processes as potential RGD-independent mechanisms of elongation and identified changes in lysophosphatidylcholine and sphingolipid secretions during RGD-mediated elongation. Implications. These results illustrate changes in phospholipid and sphingolipid metabolic processes and secretions may act as mediators of the RGD-integrin adhesion that promotes porcine conceptus elongation

Metabolic compounds within the porcine uterine environment are unique to the type of conceptus present during the early stages of blastocyst elongation

The objective of this study was to identify metabolites within the porcine uterine milieu during the early stages of blastocyst elongation. At Days 9, 10, or 11 of gestation, reproductive tracts of White cross‐bred gilts (n = 38) were collected immediately following harvest and flushed with Roswell Park Memorial Institute‐1640 medium. Conceptus morphologies were assessed from each pregnancy and corresponding uterine flushings were assigned to one of five treatment groups based on these morphologies: (a) uniform spherical (n = 8); (b) heterogeneous spherical and ovoid (n = 8); (c) uniform ovoid (n = 8); (d) heterogeneous ovoid and tubular (n = 8); and (e) uniform tubular (n = 6). Uterine flushings from these pregnancies were submitted for nontargeted profiling by gas chromatography–mass spectrometry (GC–MS) and ultra performance liquid chromatography (UPLC)–MS techniques. Unsupervised multivariate principal component analysis (PCA) was performed using pcaMethods and univariate analysis of variance was performed in R with false discovery rate (FDR) adjustment. PCA analysis of the GC–MS and UPLC–MS data identified 153 and 104 metabolites, respectively. After FDR adjustment of the GC–MS and UPLC–MS data, 38 and 59 metabolites, respectively, differed (p \u3c .05) in uterine flushings from pregnancies across the five conceptus stages. Some metabolites were greater (p \u3c .05) in abundance for uterine flushings containing earlier stage conceptuses (i.e., spherical), such as uric acid, tryptophan, and tyrosine. In contrast, some metabolites were greater (

The Continuum Directed Random Polymer

Motivated by discrete directed polymers in one space and one time dimension, we construct a continuum directed random polymer that is modeled by a continuous path interacting with a space-time white noise. The strength of the interaction is determined by an inverse temperature parameter beta, and for a given beta and realization of the noise the path evolves in a Markovian way. The transition probabilities are determined by solutions to the one-dimensional stochastic heat equation. We show that for all beta > 0 and for almost all realizations of the white noise the path measure has the same Holder continuity and quadratic variation properties as Brownian motion, but that it is actually singular with respect to the standard Wiener measure on C([0,1]).Comment: 21 page

Total synthesis and biological evaluation of simplified aplyronine analogues as synthetically tractable anticancer agents.

The aplyronines are a family of highly cytotoxic marine natural products with potential application in targeted cancer chemotherapy. To address the severe supply issue, function-oriented molecular editing of their macrolactone scaffold led to the design of a series of simplified aplyronine analogues. Enabled by a highly convergent aldol-based route, the total synthesis of four analogues was achieved, with a significant improvement in step economy versus previous compounds, and their cancer cell growth inhibition in the HeLa cell line was determined. The modular strategy presented offers a means for significantly shortening their chemical synthesis to facilitate the continued development of this promising class of anticancer agent

Spectroscopy of the spatially-extended Lya emission around a QSO at z=6.4

We have taken a deep, moderate-resolution Keck/Deimos spectra of QSO, CFHQS2329, at z=6.4. At the wavelength of Lya, the spectrum shows a spatially-extended component, which is significantly more extended than a stellar spectrum, and also a continuum part of the spectrum. The restframe line width of the extended component is 21+-7 A, and thus smaller than that of QSO (52+-4 A), where they should be identical if the light is incomplete subtraction of the QSO component. Therefore, these comparisons argue for the detection of a spatially extended Lya nebulae around this QSO. This is the first z>6 QSO that an extended Lya halo has been observed around. Careful subtraction of the central QSO spectrum reveals a lower limit to the Lya luminosity of (1.7+-0.1)x 10^43 erg s^-1. This emission may be from the theoretically predicted infalling gas in the process of forming a primordial galaxy that is ionized by a central QSO. On the other hand, if it is photoionized by the host galaxy, an estimated star-formation rate of >3.0 Msun yr^-1 is required. If we assume the gas is virialized, we obtain dynamical mass estimate of Mdyn=1.2x10^12 Msun. The derived MBH/Mhost is 2.1x10^-4, which is two orders smaller than those from more massive z~6 QSOs, and places this galaxy in accordance with the local M-sigma relation, in contrast to a previous claim on the evolution of M-sigma relation at z~6. We do not claim evolution or non-evolution of the M-sigma relation based on a single object, but our result highlights the importance of investigating fainter QSOs at z~6.Comment: 5 pages, 5 figures. Accepted for publication in MNRAS. A minor computational error fixe

A general approach for the site-selective modification of native proteins, enabling the generation of stable and functional antibody-drug conjugates.

Antibody-drug conjugates (ADCs) are a class of targeted therapeutics that utilize the specificity of antibodies to selectively deliver highly potent cytotoxins to target cells. Although recent years have witnessed significant interest in ADCs, problems remain with the standard linkage chemistries used for cytotoxin-antibody bioconjugation. These typically (1) generate unstable constructs, which may lead to premature cytotoxin release, (2) often give a wide variance in drug-antibody ratios (DAR) and (3) have poor control of attachment location on the antibody, resulting in a variable pharmacokinetic profile. Herein, we report a novel divinylpyrimidine (DVP) linker platform for selective bioconjugation via covalent re-bridging of reduced disulfide bonds on native antibodies. Model studies using the non-engineered trastuzumab antibody validate the utility of this linker platform for the generic generation of highly plasma-stable and functional antibody constructs that incorporate variable biologically relevant payloads (including cytotoxins) in an efficient and site-selective manner with precise control over DAR. DVP linkers were also used to efficiently re-bridge both monomeric and dimeric protein systems, demonstrating their potential utility for general protein modification, protein stabilisation or the development of other protein-conjugate therapeutics.AstraZeneca, Cambridge Trusts, EPSRC, BBSRC, Royal Society, MR

Global analysis of differential gene expression within the porcine conceptus transcriptome as it transitions through spherical, ovoid, and tubular morphologies during the initiation of elongation

This study aimed to identify transcriptome differences between distinct or transitional stage spherical, ovoid, and tubular porcine blastocysts throughout the initiation of elongation. We performed a global transcriptome analysis of differential gene expression using RNA‐Seq with high temporal resolution between spherical, ovoid, and tubular stage blastocysts at specific sequential stages of development from litters containing conceptus populations of distinct or transitional blastocysts. After RNA‐Seq analysis, significant differentially expressed genes (DEGs) and pathways were identified between distinct morphologies or sequential development stages. Overall, 1898 significant DEGs were identified between distinct spherical and ovoid morphologies, with 311 total DEGs between developmental stages throughout this first morphological transition, while 15 were identified between distinct ovoid and tubular, with eight total throughout these second morphological transition developmental stages. The high quantity of DEGs and pathways between conceptus stages throughout the spherical to ovoid transition suggests the importance of gene regulation during this first morphological transition for initiating elongation. Further, extensive DEG coverage of known elongation signaling pathways was illustrated from spherical to ovoid, and regulation of lipid signaling and membrane/ECM remodeling across these early conceptus stages were implicated as essential to this process, providing novel insights into potential mechanisms governing this rapid morphological change