Spectroscopic Study of Globular Clusters in the Halo of M31 with Xinglong 2.16m Telescope II: Dynamics, Metallicity and Age

(Abridged) We performed the spectroscopic observations of 11 confirmed GCs in M31 with the Xinglong 2.16m telescope and we mainly focus on the fits method and the metallicity gradient for the M31 GC sample. We analyzed and discussed more about the dynamics, metallicity and age, and their distributions as well as the relationships between these parameters. Eight more confirmed GCs in the halo of M31 were observed, most of which lack the spectroscopic information before. These star clusters are located far from the galactic center at a projected radius of ~14 to ~117 kpc. The Lick absorption-line indices and the radial velocities have been measured and ages, metallicities [Fe/H] and alpha-element [alpha/Fe] have also been fitted by comparing the observed spectral feature indices and Thomas et al.SSP model. Our results show that most of the star clusters of our sample are older than 10 Gyr except B290 ~5.5 Gyr, and most of them are metal-poor with the metallicity [Fe/H]<-1, suggesting that these clusters were born at the early stage of the galaxy's formation. We find that the metallicity gradient for the outer halo clusters with r_p>25 kpc may not exist with a slope of -0.005+-0.005 dex kpc^-1. We also find that the metallicity is not a function of age for the GCs with age < 7 Gyr while for the old GCs with age >7 Gyr there seems to be a trend that the older ones have lower metallicity. Besides, We plot metallicity distributions with the largest sample of M31 GCs so far and it shows the bimodality is not significant and the number of the metal-poor and metal-rich groups becomes comparable. The spatial distributions shows that the metal-rich group is more centrally concentrated while the metal-poor group is occupy a more extended halo and the young population is centrally concentrated while the old population is more extended spatially to the outer halo.Comment: 17 pages, 10 figures and 6 tables. Accepted for publication in RA

Closed genome and comparative phylogenetic analysis of the clinical multidrug resistant Shigella sonnei strain 866

Shigella sonneiis responsible for the majority of shigellosis infections in the US with over 500,000 cases reported annually. Here, wepresent the complete genome of the clinical multidrug resistant (MDR) strain 866, which is highly susceptible to bacteriophageinfections. The strain has a circular chromosome of 4.85 Mb and carries a 113 kb MDR plasmid. This IncB/O/K/Z-type plasmid, termedp866, confers resistance to five different classes of antibiotics including ß-lactamase, sulfonamide, tetracycline, aminoglycoside, andtrimethoprim. Comparative analysis of the plasmid architecture and gene inventory revealed that p866 shares its plasmid backbonewith previously described IncB/O/K/Z-typeShigellaspp. andEscherichiacoliplasmids, but is differentiated by the insertion of antibioticresistance cassettes, which we found associated with mobile genetic elements such as Tn3, Tn7, and Tn10. A whole genome-derivedphylogenetic reconstruction showed the evolutionary relationships ofS. sonneistrain 866 and the four establishedShigellaspecies,highlighting the clonal nature ofS. sonnei

Cutting errors in total knee replacement: Assessment by computer assisted surgery

The observed errors in the position of the implanted prosthesis can be due to a number of potential causes. One of these is the potential error during execution of the bone cuts. However, there is only minimal information on this in the current literature. The amount of cutting errors in 40 consecutive total knee replacements was reported. All the operations were done by the same surgeon. The amount of cutting error was measured by the use of computer navigation system. It was hypothesized that there was no difference in the amount of error between bone cut through the cutting slot (slotted cutting) and bone cut done on the surface of the cutting guide (open cutting). It was found that the average absolute cutting error was 1° in the coronal plane and 1.4° in the sagittal plane. Significantly more outlier (more than 3°) was observed in the errors in the sagittal plane (P = 0.014, chi square test). Open cutting resulted in less error in the sagittal plane of the tibial cut when compared with slotted cutting (P = 0.031, Mann-Whitney U Test). This was attributed by the use of a thicker saw blade with higher stiffness in the open cutting method. © 2008 Springer-Verlag.postprin

A Wide Field Survey of Satellite Galaxies around the Spiral Galaxy M106

We present a wide field survey of satellite galaxies in M106 (NGC 4258) covering a 1.7\degr \times 2\degr field around M106 using Canada-France-Hawaii Telescope/MegaCam. We find 16 satellite galaxy candidates of M106. Eight of these galaxies are found to be dwarf galaxies that are much smaller and fainter than the remaining galaxies. Four of these galaxies are new findings. Surface brightness profiles of 15 out of 16 satellite galaxies can be represented well by an exponential disk profile with varying scale length. We derive the surface number density distribution of these satellite galaxies. The central number density profile (d $<100$ kpc) is well fitted by a power-law with a power index of $-2.1\pm0.5$, similar to the expected power index of isothermal distribution. The luminosity function of these satellites is represented well by the Schechter function with a faint end slope of $-1.19^{+0.03}_{-0.06}$. Integrated photometric properties (total luminosity, total colour, and disk scale length) and the spatial distribution of these satellite galaxies are found to be roughly similar to those of the Milky Way and M31.Comment: Accepted by MNRA

The formation of professional identity in medical students: considerations for educators

&lt;b&gt;Context&lt;/b&gt; Medical education is about more than acquiring an appropriate level of knowledge and developing relevant skills. To practice medicine students need to develop a professional identity – ways of being and relating in professional contexts.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Objectives&lt;/b&gt; This article conceptualises the processes underlying the formation and maintenance of medical students’ professional identity drawing on concepts from social psychology.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Implications&lt;/b&gt; A multi-dimensional model of identity and identity formation, along with the concepts of identity capital and multiple identities, are presented. The implications for educators are discussed.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; Identity formation is mainly social and relational in nature. Educators, and the wider medical society, need to utilise and maximise the opportunities that exist in the various relational settings students experience. Education in its broadest sense is about the transformation of the self into new ways of thinking and relating. Helping students form, and successfully integrate their professional selves into their multiple identities, is a fundamental of medical education

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

Many mammals are well adapted to surviving in extremely cold environments. These species have likely accumulated genetic changes that help them efficiently cope with low temperatures. It is not known whether the same genes related to cold adaptation in one species would be under selection in another species. The aims of this study therefore were: to create a compendium of mammalian genes related to adaptations to a low temperature environment; to identify genes related to cold tolerance that have been subjected to independent positive selection in several species; to determine promising candidate genes/pathways/organs for further empirical research on cold adaptation in mammals

Improving the outcome of patients with castration-resistant prostate cancer through rational drug development

Castration-resistant prostate cancer (CRPC) is now the second most common cause of male cancer-related mortality. Although docetaxel has recently been shown to extend the survival of patients with CRPC in two large randomised phase III studies, subsequent treatment options remain limited for these patients. A greater understanding of the molecular causes of castration resistance is allowing a more rational approach to the development of new drugs and many new agents are now in clinical development. Therapeutic targets include the adrenal steroid synthesis pathway, androgen receptor signalling, the epidermal growth factor receptor family, insulin growth factor-1 receptor, histone deacetylase, heat shock protein 90 and the tumour vasculature. Drugs against these targets are giving an insight into the molecular pathogenesis of this disease and promise to improve patient quality of life and survival. Finally, the recent discovery of chromosomal translocations resulting in the upregulation of one of at least 3 ETS genes (ERG, ETV1, ETV4) may lead to novel agents for the treatment of this disease

The RR Lyrae Distance Scale

We review seven methods of measuring the absolute magnitude M_V of RR Lyrae stars in light of the Hipparcos mission and other recent developments. We focus on identifying possible systematic errors and rank the methods by relative immunity to such errors. For the three most robust methods, statistical parallax, trigonometric parallax, and cluster kinematics, we find M_V (at [Fe/H] = -1.6) of 0.77 +/- 0.13, 0.71 +/- 0.15, 0.67 +/- 0.10. These methods cluster consistently around 0.71 +/- 0.07. We find that Baade-Wesselink and theoretical models both yield a broad range of possible values (0.45-0.70 and 0.45-0.65) due to systematic uncertainties in the temperature scale and input physics. Main-sequence fitting gives a much brighter M_V = 0.45 +/- 0.04 but this may be due to a difference in the metallicity scales of the cluster giants and the calibrating subdwarfs. White-dwarf cooling-sequence fitting gives 0.67 +/- 0.13 and is potentially very robust, but at present is too new to be fully tested for systematics. If the three most robust methods are combined with Walker's mean measurement for 6 LMC clusters, V_{0,LMC} = 18.98 +/- 0.03 at [Fe/H] = -1.9, then mu_{LMC} = 18.33 +/- 0.08.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles', A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in press. 21 pages including 1 table; uses Kluwer's crckapb.sty LaTeX style file, enclose

Systemic Blockade of Clever-1 Elicits Lymphocyte Activation Alongside Checkpoint Molecule Downregulation in Patients with Solid Tumors : Results from a Phase I/II Clinical Trial

Purpose: Macrophages are critical in driving an immunosuppressive tumor microenvironment that counteracts the efficacy of T-cell-targeting therapies. Thus, agents able to reprogram macrophages toward a proinflammatory state hold promise as novel immunotherapies for solid cancers. Inhibition of the macrophage scavenger receptor Clever-1 has shown benefit in inducing CD8 T-cell-mediated antitumor responses in mouse models of cancer, which supports the clinical development of Clever-1-targeting antibodies for cancer treatment. Patients and Methods: In this study, we analyzed the mode of action of a humanized IgG4 anti-Clever-1 antibody, FP-1305 (bexmarilimab), both in vitro and in patients with heavily pretreated metastatic cancer (n = 30) participating in part 1 (dose-finding) of a phase I/II open-label trial (NCT03733990). We studied the Clever-1 interactome in primary human macrophages in antibody pull-down assays and utilized mass cytometry, RNA sequencing, and cytokine profiling to evaluate FP-1305-induced systemic immune activation in patients with cancer. Results: Our pull-down assays and functional studies indicated that FP-1305 impaired multiprotein vacuolar ATPase-mediated endosomal acidification and improved the ability of macrophages to activate CD8(+)T-cells. In patients with cancer, FP-1305 administration led to suppression of nuclear lipid signaling pathways and a proinflammatory phenotypic switch in blood monocytes. These effects were accompanied by a significant increase and activation of peripheral T-cells with indications of antitumor responses in some patients. Conclusions: Our results reveal a nonredundant role played by the receptor Clever-1 in suppressing adaptive immune cells in humans. We provide evidence that targeting macrophage scavenging activity can promote an immune switch, potentially leading to intratumoral proinflammatory responses in patients with metastatic cancer.Peer reviewe