Radical cyclisation studies of β-nitroamines from the nitro-Mannich reaction

A range of novel β-nitroacetamides with an alkenyl- or alkynyl tether were synthesized using the deprotonative or conjugate addition nitro-Mannich reaction. They were subjected to radical denitration-cyclisation with a 10 equivalent excess of tributyltin hydride, catalytic AIBN in refluxing benzene to explore the structural and electronic requirements for efficient cyclisation. Cyclisations of the β-nitroacetamides were successful in most cases, undergoing 5-exo-trig cyclisation to give the desired cyclopentyl or indanyl structures. Radical 1,4-translocation of a phenyl group was observed in several cases. Diastereoselectivity was low, with 2 or 3 of 4 possible diastereoisomers observed in most cases. Further purification by crystallisation allowed the isolation of some as single diastereoisomers. It was found that higher yields were obtained by increasing the substitution or reducing the degrees of freedom of the tether between the nitro group and the radical acceptor

Discovery of > 200 RR Lyrae Variables in M62: An Oosterhoff I Globular Cluster with a Predominantly Blue HB

We report on the discovery of a large number of RR Lyrae variable stars in the moderately metal-rich Galactic globular cluster M62 (NGC 6266), which places it among the top three most RR Lyrae-rich globular clusters known. Likely members of the cluster in our studied field, from our preliminary number counts, include about 130 fundamental-mode (RRab) pulsators, with = 0.548 d, and about 75 first-overtone (RRc) pulsators, with = 0.300 d. The average periods and the position of the RRab variables with well-defined light curves in the Bailey diagram both suggest that the cluster is of Oosterhoff type I. However, the morphology of the cluster's horizontal branch (HB) is strikingly similar to that of the Oosterhoff type II globular cluster M15 (NGC 7078), with a dominant blue HB component and a very extended blue tail. Since M15 and M62 differ in metallicity by about one dex, we conclude that metallicity, at a fixed HB type, is a key parameter determining the Oosterhoff status of a globular cluster and the position of its variables in the Bailey diagram.Comment: 5 pages, 4 figures. ApJ Letters, in pres

A Bayesian Interrupted Time Series framework for evaluating policy change on mental well-being: An application to England's welfare reform

Factors contributing to social inequalities are associated with negative mental health outcomes and disparities in mental well-being. We propose a Bayesian hierarchical controlled interrupted time series to evaluate the impact of policies on population well-being whilst accounting for spatial and temporal patterns. Using data from the UKs Household Longitudinal Study, we apply this framework to evaluate the impact of the UKs welfare reform implemented in the 2010s on the mental health of the participants, measured using the GHQ-12 index. Our findings indicate that the reform led to a 2.36% (95% CrI: 0.57%–4.37%) increase in the national GHQ-12 index in the exposed group, after adjustment for the control group. Moreover, the geographical areas that experienced the largest increase in the GHQ-12 index are from more disadvantage backgrounds than affluent backgrounds

New period-luminosity and period-color relations of classical Cepheids: III. Cepheids in SMC

The photometric data for 460 classical, fundamental-mode Cepheids in the SMC with log P > 0.4 measured by Udalski et al. have been analyzed for their P-C and P-L relations, and for the variation of amplitude across the instability strip in a similar way that was done in Papers I and II of this series. The SMC Cepheids are bluer in (B-V) at a given period than for both the Galaxy and the LMC. Their P-C relation in (B-V) is best fit by two lines intersecting at P=10 d. Their break must necessarily exist also in the P-L relations in B and/or V, but remains hidden in the magnitude scatter. An additional pronounced break of the P-L relations in B, V, and I occurs at P=2.5 d. The observed slope of the lines of constant period in the HR diagram agrees with the theoretical expectation from the pulsation equation. The largest amplitude Cepheids for periods less than 13 days occur near the blue edge of the instability strip. The sense is reversed in the period interval from 13 to 20 days, as in the Galaxy and the LMC. The SMC P-L relation is significantly flatter than that for the Galaxy, NGC 3351, 4321, M31, all of which have nearly the same steep slope. The SMC P-L slope is intermediate between that of these steep slope cases and the very shallow slope of Cepheids in the lower metallicity galaxies of NGC 3109 and Sextans A/B, consistent with the premise that the Cepheid P-L relation varies from galaxy-to-galaxy as function of metallicity. Failure to take into account the slope differences in the P-L relation as a function of metallicity using Cepheids as distance indicators results in incorrect Cepheid distances. Part of the 15% difference between our long distance scale - now independently supported by TRGB distances - and that of the HST Key Project short scale is due to the effect of using an inappropriate P-L relation.Comment: 9 pages, 10 figures, accepted for publication in Astronomy & Astrophysic

Temperature Differences in the Cepheid Instability Strip Require Differences in the Period-Luminosity Relation in Slope and Zero Point

A graphical and an algebraic demonstration is made to show why the slope and zero point of the Cepheid period-luminosity (P-L) relation is rigidly coupled with the slope and zero point of the Cepheid instability strip in the HR diagram. The graphical demonstration uses an arbitrary (toy) ridge line in the instability strip, while the algebraic demonstration uses the pulsation equation into which the observed P-L relations for the Galaxy and the LMC are put to predict the temperature zero points and slopes of the instability strips. Agreement between the predicted and measured instability strip slopes argue that the observed P-L differences between the Galaxy and LMC are real. In another proof, the direct evidence for different P-L slopes in different galaxies is shown by comparing the Cepheid data in the Galaxy, the combined data in NGC 3351 and NGC 4321, in M31, LMC, SMC, IC 1613, NGC 3109, and in Sextans A+B. The P-L slopes for the Galaxy, NGC 3351, NGC 4321, and M31 are nearly identical and are the steepest in the sample. The P-L slopes decrease monotonically with metallicity in the order listed, showing that the P-L relation is not the same in different galaxies, complicating their use in calibrating the extragalactic distance scale.Comment: 15 pages, 1 table, 4 figures, submitted to The Ap

Classical Cepheid Pulsation Models. III. The Predictable Scenario

Within the current uncertainties in the treatment of the coupling between pulsation and convection, limiting amplitude, nonlinear, convective models appear the only viable approach for providing theoretical predictions about the intrinsic properties of radial pulsators. In this paper we present the results of a comprehensive set of Cepheid models computed within such theoretical framework for selected assumptions on their original chemical composition.Comment: 24 pages, 1 latex file containing 6 tables, 10 postscript figures, accepted for publication on Ap

Structure of the Large Magellanic Cloud from 2MASS

We derive structural parameters and evidence for extended tidal debris from star count and preliminary standard candle analyses of the Large Magellanic Cloud based on Two Micron All Sky Survey (2MASS) data. The full-sky coverage and low extinction in K_s presents an ideal sample for structural analysis of the LMC. The star count surface densities and deprojected inclination for both young and older populations are consistent with previous work. We use the full areal coverage and large LMC diameter to Galactrocentric distance ratio to infer the same value for the disk inclination based on perspective. A standard candle analysis based on a sample of carbon long-period variables (LPV) in a narrow color range, 1.6<J-K_s<1.7 allows us to probe the three-dimensional structure of the LMC along the line of sight. The intrinsic brightness distribution of carbon LPVs in selected fields implies that \sigma_M\simlt 0.2^m for this color cut. The sample provides a {\it direct} determination of the LMC disk inclination: $42.3^\circ\pm 7.2^\circ$. Distinct features in the photometric distribution suggest several distinct populations. We interpret this as the presence of an extended stellar component of the LMC, which may be as thick as 14 kpc, and intervening tidal debris at roughly 15 kpc from the LMC.Comment: 24 pages, 9 figures. Submitted to Ap

Intermediate-mass star models with different helium and metal contents

We present a comprehensive theoretical investigation of the evolutionary properties of intermediate-mass stars. The evolutionary sequences were computed from the Zero Age Main Sequence up to the central He exhaustion and often up to the phases which precede the carbon ignition or to the reignition of the H-shell which marks the beginning of the thermal pulse phase. The evolutionary tracks were constructed by adopting a wide range of stellar masses ($3\leq$\msun$\leq15$) and chemical compositions. In order to account for current uncertainties on the He to heavy elements enrichment ratio, the stellar models were computed by adopting at Z=0.02 two different He contents (Y=0.27, 0.289) and at Z=0.04 three different He contents (Y=0.29, 0.34, and 0.37). To supply a homogeneous evolutionary scenario which accounts for young Magellanic stellar systems the calculations were also extended toward lower metallicities (Z=0.004, Z=0.01), by adopting different initial He abundances. We evaluated for both solar (Z=0.02) and super-metal-rich (SMR, Z=0.04) models the transition mass $M^{up}$ between the stellar structures igniting carbon and those which develop a full electron degeneracy inside the CO core. This evolutionary scenario allows us to investigate in detail the properties of classical Cepheids. In particular, we find that the range of stellar masses which perform the blue loop during the central He-burning phase narrows when moving toward metal-rich and SMR structures.Comment: 25 pages, 10 figures (4 postscript + 6 gif files), 7 postscript tables. accepted for publication on ApJ (November 2000

Genomic positional conservation identifies topological anchor point (tap)RNAs linked to developmental loci

The mammalian genome is transcribed into large numbers of long noncoding RNAs (lncRNAs), but the definition of functional lncRNA groups has proven difficult, partly due to their low sequence conservation and lack of identified shared properties. Here we consider positional conservation across mammalian genomes as an indicator of functional commonality. We identify 665 conserved lncRNA promoters in mouse and human genomes that are preserved in genomic position relative to orthologous coding genes. The identified positionally conserved lncRNA genes are primarily associated with developmental transcription factor loci with which they are co-expressed in a tissue-specific manner. Strikingly, over half of all positionally conserved RNAs in this set are linked to distinct chromatin organization structures, overlapping the binding sites for the CTCF chromatin organizer and located at chromatin loop anchor points and borders of topologically associating domains (TADs). These topological anchor point (tap)RNAs possess conserved sequence domains that are enriched in potential recognition motifs for Zinc Finger proteins. Characterization of these non-coding RNAs and their associated coding genes shows that they are functionally connected: they regulate each other ′s expression and influence the metastatic phenotype of cancer cells in vitro in a similar fashion. Thus, interrogation of positionally conserved lncRNAs identifies a new subset of tapRNAs with shared functional properties. These results provide a large dataset of lncRNAs that conform to the ″extended gene″ model, in which conserved developmental genes are genomically and functionally linked to regulatory lncRNA loci across mammalian evolution

Targeting the Mitotic Checkpoint to Kill Tumor Cells

One of the most common hallmarks of cancer cells is aneuploidy or an abnormal number of chromosomes. This abnormal chromosome content is a consequence of chromosome missegregation during mitosis, a defect that is seen more frequently in tumor cell divisions as in normal cell divisions. In fact, a large fraction of human tumors display a chromosome instable phenotype, meaning that they very frequently missegregate chromosomes. This can cause variegated aneuploidy within the tumor tissue. It has been argued that this hallmark of cancer could be exploited in anti-cancer therapies. Here we test this hypothesis by inactivation of the mitotic checkpoint through RNAi-mediated depletion of an essential checkpoint component, Mps1. The mitotic checkpoint delays segregation of chromosomes during mitosis until all chromosomes are properly attached to the mitotic spindle. Its inactivation will therefore lead to increased segregation errors. Indeed, we show that this can lead to increased cell death in tumor cells. We demonstrate that increased cell death is associated with a dramatic increase in segregation errors. This suggests that inhibition of the mitotic checkpoint might represent a useful anti-cancer strategy