Globular Clusters in the dE,N galaxy NGC 3115 DW1: New Insights from Spectroscopy and HST Photometry

The properties of globular clusters in dwarf galaxies are key to understanding the formation of globular cluster systems, and in particular in verifying scenarios in which globular cluster systems of larger galaxies formed (at least partly) from the accretion of dwarf galaxies. Here, we revisit the globular cluster system of the dE,N galaxy NGC 3115 DW1 - a companion of the nearby S0 galaxy NGC 3115 - adding Keck/LRIS spectroscopy and HST/WFPC2 imaging to previous ground-based photometry. Spectra for seven globular clusters reveal normal abundance ratios with respect to the Milky Way and M31 clusters, as well as a relatively high mean metallicity ([Fe/H] = -1.0+/-0.1 dex). Crude kinematics indicate a high velocity dispersion within 10 kpc which could either be caused by dark matter dominated outer regions, or by the stripping of outer globular clusters by the nearby giant galaxy NGC 3115. The total galaxy mass out to 3 and 10 kpc lies between 10^10 and 10^11 solar masses and 2*10^10 and 4*10^11 solar masses, respectively, depending on the mass estimator used and the assumptions on cluster orbits and systemic velocity. The HST imaging allows measurement of sizes for two clusters, returning core radii around 2.0 pc, similar to the sizes observed in other galaxies. Spectroscopy allows an estimate of the degree of contamination by foreground stars or background galaxies for the previous ground-based photometry, but does not require a revision of previous results: NGC 3115 DW1 hosts around 60+/-20 clusters which corresponds to a specific frequency of 4.9+/-1.9, on the high end for massive dEs. Given its absolute magnitude (M_V=-17.7 mag) and the properties of its cluster system, NGC 3115 DW1 appears to be a transition between a luminous dE and low-luminosity E galaxy.Comment: 25 pages, 8 figures, accepted for publication in The Astronomical Journal, August 2000 issu

Star-Forming Galaxies at z~2 and the Formation of the Metal-Rich Globular Cluster Population

We examine whether the super star-forming clumps (R~1-3 kpc; M~10^8-10^9.5 Msun) now known to be a key component of star-forming galaxies at z~2 could be the formation sites of the locally observed old globular cluster population. We find that the stellar populations of these super star-forming clumps are excellent matches to those of local metal-rich globular clusters. Moreover, this globular cluster population is known to be associated with the bulges / thick disks of galaxies, and we show that its spatial distribution and kinematics are consistent with the current understanding of the assembly of bulges and thick disks from super star-forming clumps at high redshift. Finally, with the assumption that star formation in these clumps proceeds as a scaled-up version of local star formation in molecular clouds, this formation scenario reproduces the observed numbers and mass spectra of metal-rich globular clusters. The resulting link between the turbulent and clumpy disks observed in high-redshift galaxies and a local globular cluster population provides a plausible co-evolutionary scenario for several of the major components of a galaxy: the bulge, the thick disk, and one of the globular cluster populations.Comment: Accepted for publication in MNRAS Letters. 5 pages, 2 figure

Smooth-Muscle BMAL1 Participates in Blood Pressure Circadian Rhythm Regulation

As the central pacemaker, the suprachiasmatic nucleus (SCN) has long been considered the primary regulator of blood pressure circadian rhythm; however, this dogma has been challenged by the discovery that each of the clock genes present in the SCN is also expressed and functions in peripheral tissues. The involvement and contribution of these peripheral clock genes in the circadian rhythm of blood pressure remains uncertain. Here, we demonstrate that selective deletion of the circadian clock transcriptional activator aryl hydrocarbon receptor nuclear translocator-like (Bmal1) from smooth muscle, but not from cardiomyocytes, compromised blood pressure circadian rhythm and decreased blood pressure without affecting SCN-controlled locomotor activity in murine models. In mesenteric arteries, BMAL1 bound to the promoter of and activated the transcription of Rho-kinase 2 (Rock2), and Bmal1 deletion abolished the time-of-day variations in response to agonist-induced vasoconstriction, myosin phosphorylation, and ROCK2 activation. Together, these data indicate that peripheral inputs contribute to the daily control of vasoconstriction and blood pressure and suggest that clock gene expression outside of the SCN should be further evaluated to elucidate pathogenic mechanisms of diseases involving blood pressure circadian rhythm disruption

New Light on the Formation and Evolution of M31 and its Globular Cluster System

We present spectroscopic ages, metallicities, and [alpha/Fe] ratios for 70 globular clusters in M31 that were derived from Lick line-index measurements. In addition to a population of old (>10 Gyr) globular clusters with a wide range of metallicities, from about -2.0 dex to solar values, we find evidence for a population of intermediate-age globular clusters with ages between ~5 and 8 Gyr and a mean metallicity around [Z/H]=-0.6. We also confirm the presence of young M31 globular clusters that were recently identified by Beasley et al. (2004), which have ages <1 Gyr and relatively high metallicities around -0.4 dex. The M31 globular cluster system has a clearly super-solar mean [alpha/Fe]=0.14\pm0.04 dex. Intermediate-age and young objects show roughly solar abundance ratios. We find evidence for an age-[alpha/Fe] relation in the sense that younger clusters have smaller mean [alpha/Fe] ratios. From a comparison of indices, mostly sensitive to carbon and/or nitrogen abundance, with SSP model predictions for nitrogen-enhanced stellar populations, we find a dichotomy in nitrogen enhancement between young and old M31 globular clusters. The indices of objects older than 5 Gyr are consistent with a factor of three or higher in nitrogen enhancement compared to their younger counterparts. Using kinematical data from Morrison et al. (2004) we find that the globular cluster sub-population with halo kinematics is old (>9 Gyr), has a bimodal metallicity distribution, and super-solar [alpha/Fe]. Disk globular clusters have a wider range of ages, are on average more metal-rich, and have a slightly smaller mean [alpha/Fe] ratio. (abridged)Comment: 32 pages, 12 figures, accepted for publication in A&

PCR-free method detects high frequency of genomic instability in prostate cancer

Most studies of tumor instability are PCR-based. PCR-based methods may underestimate mutation frequencies of heterogeneous tumor genomes. Using a novel PCR-free random cloning/sequencing method, we analyzed 100 kb of total genomic DNA from blood lymphocytes, normal prostate and tumor prostate taken from six individuals. Variations were identified by comparison of the sequence of the cloned fragments with the nr-database in Genbank. After excluding known polymorphisms (by comparison to the NCBI dbSNP), we report a significant over-representation of variants in the tumors: 0.66 variations per kilobase of sequence, compared with the corresponding normal prostates (0.14 variations/kb) or blood (0.09 variations/kb). Extrapolating the observed difference between tumor and normal prostate DNA, we estimate 1.8 million somatic (de novo) alterations per tumor cell genome, a much higher frequency than previous measurements obtained by mostly PCR-based methods in other tumor types. Moreover, unlike the normal prostate and blood, most of the tumor variations occur in a specific motif (P = 0.046), suggesting common etiology. We further report high tumor cell-to-cell heterogeneity. These data have important implications for selecting appropriate technologies for cancer genome projects as well as for understanding prostate cancer progression

What we talk about when we talk about "global mindset": managerial cognition in multinational corporations

Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as “global mindset” that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p &lt; 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM &gt; 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM &gt; 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

Search for the Standard Model Higgs Boson with the OPAL Detector at LEP

This paper summarises the search for the Standard Model Higgs boson in e+e- collisions at centre-of-mass energies up to 209 GeV performed by the OPAL Collaboration at LEP. The consistency of the data with the background hypothesis and various Higgs boson mass hypotheses is examined. No indication of a signal is found in the data and a lower bound of 112.7GeV/C^2 is obtained on the mass of the Standard Model Higgs boson at the 95% CL.Comment: 51 pages, 21 figure