Synthesis and applications of 2,4-disubstituted thiazoles derivatives as small molecule modulators of cellular development

Understanding how the structure of molecules relates to their function and biological activity is essential in the development of new analogues with targeted activity. This is especially relevant in mediating developmental processes in mammalian cells and the regulation of stem cell differentiation. In this study, thiazole-containing small molecules were synthesised and investigated for their ability to induce the differentiation of human pluripotent stem cells and their derivatives. Analyses of cell morphology, cell viability, expression of cell surface markers and ability to induce cell differentiation and regulate neurite formation identified the analogue with the longest and most bulky hydrophobic side chain as possessing comparable or enhanced activity to all-trans-retinoic acid (ATRA). Interestingly, a shorter, less bulky, known thiazole compound reported to be isoform selective for the retinoic acid receptor β2 (RARβ2) agonist did not mediate differentiation under the conditions tested; however, activity could be restored by adjusting the structure to a longer, more bulky molecule. These data provide further insight into the complexity of compound design in terms of developing small molecules with specific biological activities to control the development and differentiation of mammalian cells

In re Arbitration between the Italian Republic and the Republic of India concerning the “Enrica Lexie” incident

On May 21, 2020, a Tribunal established under Annex VII of the United Nations Convention on the Law of the Sea (UNCLOS) rendered an Award regarding the 2012 Enrica Lexie incident, which involved the death of two Indian fishermen at the hands of Italian Marines. The Award is lengthy and wide-ranging, finding that: (1) Italy and India had concurrent jurisdiction over the incident; (2) the Tribunal had incidental jurisdiction to determine the immunity of the Italian Marines; (3) the Marines enjoyed immunity as state officials; but nevertheless that (4) India was entitled to compensation for the loss of life, physical harm, damage to property, and moral harm. The Award has been received more positively by Italy than India, but neither party has indicated that they intend to do anything other than comply with it

The Evolution of Early-type Field Galaxies Selected from a NICMOS Map of the Hubble Deep Field North

The redshift distribution of well-defined samples of distant early-type galaxies offers a means to test the predictions of monolithic and hierarchical galaxy formation scenarios. NICMOS maps of the entire Hubble Deep Field North in the F110W and F160W filters, when combined with the available WFPC2 data, allow us to calculate photometric redshifts and determine the morphological appearance of galaxies at rest-frame optical wavelengths out to z ~ 2.5. Here we report results for two subsamples of early-type galaxies, defined primarily by their morphologies in the F160W band, which were selected from the NICMOS data down to H160_{AB} < 24.0. The observed redshift distributions of our two early-type samples do not match that predicted by a monolithic collapse model, which shows an overabundance at z > 1.5. A hierarchical formation model better matches the redshift distribution of the HDF-N early-types at z > 1.5, but still does not adequately describe the observed early-types. The hierarchical model predicts significantly bluer colors on average than the observed early-type colors, and underpredicts the observed number of early-types at z < 1. [abridged]Comment: Accepted for publication in the Astronomical Journal; 54 pages, 21 figures. Figures 10 and 11 are included separately in JPEG forma

Community professionals' management of client care : a mixed-methods systematic review

This is the final draft, after peer-review, of a manuscript published in Journal of Health Services Research & Policy. The definitive version, detailed above, is available online at www.rsmjournals.com.Peer reviewedPostprin

Red and Reddened Quasars in the Sloan Digital Sky Survey

We investigate the continuum and emission line properties of 4576 SDSS quasars as a function of their optical/UV SEDs. The optical/UV color distribution of our sample is roughly Gaussian, but with a red tail; we distinguish between 1) intrinsically blue (optically flat) quasars, 2) intrinsically red (optically steep) quasars, and 3) the 273 (6%) of our quasars whose continua are inconsistent with a single power-law and appear redder due to SMC-like dust reddening rather than synchrotron emission. The color distribution suggests that the population of moderately dust reddened broad-line quasars is smaller than that of unobscured quasars, but we estimate that a further 10% of the luminous quasar population is missing from the SDSS sample because of dust extinction with E(B-V)<0.5. We also investigate the emission and absorption line properties of these quasars as a function of color with regard to Boroson & Green type eigenvectors. Intrinsically red (optically steep) quasars tend to have narrower Balmer lines and weaker CIV, CIII], HeII and 3000A bump emission as compared with bluer (optically flatter) quasars. The change in strength of the 3000A bump appears to be dominated by the Balmer continuum and not by FeII emission. The dust reddened quasars have even narrower Balmer lines and weaker 3000A bumps, in addition to having considerably larger equivalent widths of [OII] and [OIII] emission. The fraction of broad absorption line quasars (BALQSOs) increases from ~3.4% for the bluest quasars to perhaps as large as 20% for the dust reddened quasars, but the intrinsic color distribution is affected by dust reddening. (abridged)Comment: 37 pages, 10 figures (3 color), 2 tables, accepted by AJ. For a version with higher quality figures, see ftp://astro.princeton.edu/gtr/redqsos/RichardsGT_redqsos.revised3.preprint.p

Homoplasy corrected estimation of genetic similarity from AFLP bands, and the effect of the number of bands on the precision of estimation

AFLP is a DNA fingerprinting technique, resulting in binary band presence–absence patterns, called profiles, with known or unknown band positions. We model AFLP as a sampling procedure of fragments, with lengths sampled from a distribution. Bands represent fragments of specific lengths. We focus on estimation of pairwise genetic similarity, defined as average fraction of common fragments, by AFLP. Usual estimators are Dice (D) or Jaccard coefficients. D overestimates genetic similarity, since identical bands in profile pairs may correspond to different fragments (homoplasy). Another complicating factor is the occurrence of different fragments of equal length within a profile, appearing as a single band, which we call collision. The bias of D increases with larger numbers of bands, and lower genetic similarity. We propose two homoplasy- and collision-corrected estimators of genetic similarity. The first is a modification of D, replacing band counts by estimated fragment counts. The second is a maximum likelihood estimator, only applicable if band positions are available. Properties of the estimators are studied by simulation. Standard errors and confidence intervals for the first are obtained by bootstrapping, and for the second by likelihood theory. The estimators are nearly unbiased, and have for most practical cases smaller standard error than D. The likelihood-based estimator generally gives the highest precision. The relationship between fragment counts and precision is studied using simulation. The usual range of band counts (50–100) appears nearly optimal. The methodology is illustrated using data from a phylogenetic study on lettuce

New Method to Calculate the Sign and Relative Strength of Magnetic Interactions in Low-Dimensional Systems on the Basis of Structural Data

The connection of strength of magnetic interactions and type ordering the magnetic moments with crystal chemical characteristics in low-dimensional magnets is investigated. The new method to calculate the sign and relative strength of magnetic interactions in low-dimensional systems on the basis of the structural data is proposed. This method allows to estimate magnetic interactions not only inside low-dimensional fragments but also between them, and also to predict the possibility of the occurrence of magnetic phase transitions and anomalies of the magnetic interactions. Moreover, it can be used for search of low-dimensional magnets among the compounds whose crystal structures are known. The possibilities of the method are illustrated in an example of research of magnetic interactions in familiar low-dimensional magnets SrCu2(BO3)2, CaCuGe2O6, CaV4O9, Cu2Te2O5Cl2, Cu2Te2O5Br2, BaCu2Si2O7, BaCu2Ge2O7, BaCuSi2O6, LiCu2O2, and NaCu2O2.Comment: 18 pages, 8 figures, 2 tables, published versio

Detection of segregation distortion loci in triticale (x Triticosecale Wittmack) based on a high-density DArT marker consensus genetic linkage map

<p>Abstract</p> <p>Background</p> <p>Triticale is adapted to a wide range of abiotic stress conditions, is an important high-quality feed stock and produces similar grain yield but more biomass compared to other crops. Modern genomic approaches aimed at enhancing breeding progress in cereals require high-quality genetic linkage maps. Consensus maps are genetic maps that are created by a joint analysis of the data from several segregating populations and different approaches are available for their construction. The phenomenon that alleles at a locus deviate from the Mendelian expectation has been defined as segregation distortion. The study of segregation distortion is of particular interest in doubled haploid (DH) populations due to the selection pressure exerted on the plants during the process of their establishment.</p> <p>Results</p> <p>The final consensus map, constructed out of six segregating populations derived from nine parental lines, incorporated 2555 DArT markers mapped to 2602 loci (1929 unique). The map spanned 2309.9 cM with an average number of 123.9 loci per chromosome and an average marker density of one unique locus every 1.2 cM. The R genome showed the highest marker coverage followed by the B genome and the A genome. In general, locus order was well maintained between the consensus linkage map and the component maps. However, we observed several groups of loci for which the colinearity was slightly uneven. Among the 2602 loci mapped on the consensus map, 886 showed distorted segregation in at least one of the individual mapping populations. In several DH populations derived by androgenesis, we found chromosomes (2B, 3B, 1R, 2R, 4R and 7R) containing regions where markers exhibited a distorted segregation pattern. In addition, we observed evidence for segregation distortion between pairs of loci caused either by a predominance of parental or recombinant genotypes.</p> <p>Conclusions</p> <p>We have constructed a reliable, high-density DArT marker consensus genetic linkage map as a basis for genomic approaches in triticale research and breeding, for example for multiple-line cross QTL mapping experiments. The results of our study exemplify the tremendous impact of different DH production techniques on allele frequencies and segregation distortion covering whole chromosomes.</p