Kinematically Cold Populations at Large Radii in the Draco and Ursa Minor Dwarf Spheroidals

We present projected velocity dispersion profiles for the Draco and Ursa Minor (UMi) dwarf spheroidal galaxies based on 207 and 162 discrete stellar velocities, respectively. Both profiles show a sharp decline in the velocity dispersion outside ~30 arcmin (Draco) and ~40 arcmin (UMi). New, deep photometry of Draco reveals a break in the light profile at ~25 arcmin. These data imply the existence of a kinematically cold population in the outer parts of both galaxies. Possible explanations of both the photometric and kinematic data in terms of both equilibrium and non-equilibrium models are discussed in detail. We conclude that these data challenge the picture of dSphs as simple, isolated stellar systems.Comment: 5 pages, accepted for publication in ApJ Letter

Smoothed universal correlations in the two-dimensional Anderson model

We report on calculations of smoothed spectral correlations in the two-dimensional Anderson model for weak disorder. As pointed out in (M. Wilkinson, J. Phys. A: Math. Gen. 21, 1173 (1988)), an analysis of the smoothing dependence of the correlation functions provides a sensitive means of establishing consistency with random matrix theory. We use a semiclassical approach to describe these fluctuations and offer a detailed comparison between numerical and analytical calculations for an exhaustive set of two-point correlation functions. We consider parametric correlation functions with an external Aharonov-Bohm flux as a parameter and discuss two cases, namely broken time-reversal invariance and partial breaking of time-reversal invariance. Three types of correlation functions are considered: density-of-states, velocity and matrix element correlation functions. For the values of smoothing parameter close to the mean level spacing the semiclassical expressions and the numerical results agree quite well in the whole range of the magnetic flux.Comment: 12 pages, 14 figures submitted to Phys. Rev.

Effect of Finite Mass on Primordial Nucleosynthesis

We have calculated the small effect of finite nucleon mass on the weak-interaction rates that interconvert protons and neutrons in the early Universe. We have modified the standard code for primordial nucleosynthesis to include these corrections and find a small, systematic increase in the 4He yield, $\delta Y / Y \simeq (0.47 - 0.50)$, depending slightly on the baryon-to-photon ratio. The fractional changes in the abundances of the other light elements are a few percent or less for interesting values of the baryon-to-photon ratio.Comment: 15 pages, 8 figures, uses psfig.st

Ultra-low temperature structure determination of a Mn12 single-molecule magnet and the interplay between lattice solvent and structural disorder

We have determined the ultra-low temperature crystal structure of the archetypal single-molecule magnet (SMM) [Mn12O12(O2CMe)16(H2O)4]·4H2O·2MeCO2H (1) at 2 K, by using a combination of single-crystal X-ray and single-crystal neutron diffraction. This is the first structural study of any SMM in the same temperature regime where slow magnetic relaxation occurs. We reveal an additional hydrogen bonding interaction between the {Mn12} cluster and its solvent of crystallisation, which shows how the lattice solvent transmits disorder to the acetate ligands in the {Mn12} complex. Unusual quantum properties observed in 1 have long been attributed to disorder. Hence, we studied the desolvation products of 1, in order to understand precisely the influence of lattice solvent on the structure of the cluster. We present two new axially symmetric structures corresponding to different levels of desolvation of 1, [Mn12O12(O2CMe)16(H2O)4]·4H2O (2) and [Mn12O12(O2CMe)16(H2O)4] (3). In 2, removal of acetic acid of crystallisation largely resolves positional disorder in the affected acetate ligands, whereas removal of lattice water molecules further resolves the acetate ligand disorder in 3. Due to the absence of acetic acid of crystallisation, both 2 and 3 have true, unbroken S4 symmetry, showing for the first time that it is possible to prepare fully axial Mn12–acetate analogues from 1, via single-crystal to single-crystal transformations

A One-sided, Highly Relativistic Jet from Cygnus X-3

Very Long Baseline Array images of the X-ray binary, Cygnus X-3, were obtained 2, 4 and 7 days after the peak of a 10 Jy flare on 4 February 1997. The first two images show a curved one-sided jet, the third a scatter-broadened disc, presumably at the position of the core. The jet curvature changes from the first to the second epoch, which strongly suggests a precessing jet. The ratio of the flux density in the approaching to that in the (undetected) receding jet is > 330; if this asymmetry is due to Doppler boosting, the implied jet speed is > 0.81c. Precessing jet model fits, together with the assumptions that the jet is intrinsically symmetric and was ejected during or after the major flare, yield the following constraints: the jet inclination to the line of sight must be < 14 degrees; the cone opening angle must be < 12 degrees; and the precession period must be > 60 days.Comment: 12 pages 7 figures, accepted by Ap

Precision Prediction for the Big-Bang Abundance of Primordial Helium

Within the standard models of particle physics and cosmology we have calculated the big-bang prediction for the primordial abundance of \he to a theoretical uncertainty of less than 0.1 \pct $(\delta Y_P < \pm 0.0002)$, improving the current theoretical precision by a factor of 10. At this accuracy the uncertainty in the abundance is dominated by the experimental uncertainty in the neutron mean lifetime, $\tau_n = 885.4 \pm 2.0 sec$. The following physical effects were included in the calculation: the zero and finite-temperature radiative, Coulomb and finite-nucleon-mass corrections to the weak rates; order-$\alpha$ quantum-electrodynamic correction to the plasma density, electron mass, and neutrino temperature; and incomplete neutrino decoupling. New results for the finite-temperature radiative correction and the QED plasma correction were used. In addition, we wrote a new and independent nucleosynthesis code designed to control numerical errors to be less than 0.1\pct. Our predictions for the \EL[4]{He} abundance are presented in the form of an accurate fitting formula. Summarizing our work in one number, $Y_P(\eta = 5\times 10^{-10}) = 0.2462 \pm 0.0004 (expt) \pm < 0.0002 (theory)$. Further, the baryon density inferred from the Burles-Tytler determination of the primordial D abundance, $\Omega_B h^2 = 0.019\pm 0.001$, leads to the prediction: $Y_P = 0.2464 \pm 0.0005 (D/H) \pm < 0.0002 (theory) \pm 0.0005 (expt)$. This ``prediction'' and an accurate measurement of the primeval \he abundance will allow an important consistency test of primordial nucleosynthesis.Comment: Replaced fitting formulas - new versions differ by small but significant amount. Other minor changes. 30 pages, 17 figures, 5 table

Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors

Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals (≥ 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG-I agonists compared to cells obtained from adults (≤ 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro-inflammatory and antiviral cytokines and chemokines including TNFα, IL-6, IL-1β, IFNα, IFNγ, CCL2, and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up-regulation of PD-L1 on monocytes and T cells, and increased expression of PD-L2 and B7-H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR-stimulated PBMCs (minus CD3 T cells) from old subjects elicited significantly lower levels of adult T-cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age-associated changes in cytokine, chemokine and interferon production, as well as co-stimulatory protein expression could contribute to the blunted memory B- and T-cell immune responses to vaccines and infections

Characteristics of outdoor falls among older people: A qualitative study

Background Falls are a major threat to older people’s health and wellbeing. Approximately half of falls occur in outdoor environments but little is known about the circumstances in which they occur. We conducted a qualitative study to explore older people’s experiences of outdoor falls to develop understanding of how they may be prevented. Methods We conducted nine focus groups across the UK (England, Wales, and Scotland). Our sample was from urban and rural settings and different environmental landscapes. Participants were aged 65+ and had at least one outdoor fall in the past year. We analysed the data using framework and content analyses. Results Forty-four adults aged 65 – 92 took part and reported their experience of 88 outdoor falls. Outdoor falls occurred in a variety of contexts, though reports suggested the following scenarios may have been more frequent: when crossing a road, in a familiar area, when bystanders were around, and with an unreported or unknown attribution. Most frequently, falls resulted in either minor or moderate injury, feeling embarrassed at the time of the fall, and anxiety about falling again. Ten falls resulted in fracture, but no strong pattern emerged in regard to the contexts of these falls. Anxiety about falling again appeared more prevalent among those that fell in urban settings and who made more visits into their neighbourhood in a typical week. Conclusions This exploratory study has highlighted several aspects of the outdoor environment that may represent risk factors for outdoor falls and associated fear of falling. Health professionals are recommended to consider outdoor environments as well as the home setting when working to prevent falls and increase mobility among older people

The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer

The contractile actin-myosin cytoskeleton provides much of the force required for numerous cellular activities such as motility, adhesion, cytokinesis and changes in morphology. Key elements that respond to various signal pathways are the myosin II regulatory light chains (MLC), which participate in actin-myosin contraction by modulating the ATPase activity and consequent contractile force generation mediated by myosin heavy chain heads. Considerable effort has focussed on the role of MLC kinases, and yet the contributions of the myotonic dystrophy-related Cdc42-binding kinases (MRCK) proteins in MLC phosphorylation and cytoskeleton regulation have not been well characterized. In contrast to the closely related ROCK1 and ROCK2 kinases that are regulated by the RhoA and RhoC GTPases, there is relatively little information about the CDC42-regulated MRCKα, MRCKβ and MRCKγ members of the AGC (PKA, PKG and PKC) kinase family. As well as differences in upstream activation pathways, MRCK and ROCK kinases apparently differ in the way that they spatially regulate MLC phosphorylation, which ultimately affects their influence on the organization and dynamics of the actin-myosin cytoskeleton. In this review, we will summarize the MRCK protein structures, expression patterns, small molecule inhibitors, biological functions and associations with human diseases such as cancer

A high-resolution map of human evolutionary constraint using 29 mammals.

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease