Magellanic Cloud Periphery Carbon Stars IV: The SMC

The kinematics of 150 carbon stars observed at moderate dispersion on the periphery of the Small Magellanic Cloud are compared with the motions of neutral hydrogen and early type stars in the Inter-Cloud region. The distribution of radial velocities implies a configuration of these stars as a sheet inclined at 73+/-4 degrees to the plane of the sky. The near side, to the South, is dominated by a stellar component; to the North, the far side contains fewer carbon stars, and is dominated by the neutral gas. The upper velocity envelope of the stars is closely the same as that of the gas. This configuration is shown to be consistent with the known extension of the SMC along the line of sight, and is attributed to a tidally induced disruption of the SMC that originated in a close encounter with the LMC some 0.3 to 0.4 Gyr ago. The dearth of gas on the near side of the sheet is attributed to ablation processes akin to those inferred by Weiner & Williams (1996) to collisional excitation of the leading edges of Magellanic Stream clouds. Comparison with pre LMC/SMC encounter kinematic data of Hardy, Suntzeff, & Azzopardi (1989) of carbon stars, with data of stars formed after the encounter, of Maurice et al. (1989), and Mathewson et al. (a986, 1988) leaves little doubt that forces other than gravity play a role in the dynamics of the H I.Comment: 30 pages; 7 figures, latex compiled, 1 table; to appear in AJ (June 2000

Functional analysis of the mismatch repair system in bladder cancer

In bladder cancer the observed microsatellite instability indicates that mismatch repair deficiency could be a frequently involved factor in bladder cancer progression. To investigate this hypothesis we analysed extracts of seven bladder cancer cell lines and, as a novel approach, five clinical cancer samples for mismatch repair activity. We found that one cell line (T24) and three of the clinical samples had a reduced repair capacity, measured to ~20% or less. The T24 cell extract was unable to repair a G-G mismatch and showed reduced repair of a 2-base loop, consistent with diminished function of the MSH2-MSH6 heterodimer. The functional assay was combined with measurement for mutation frequency, microsatellite analysis, sequencing, MTT assay, immunohistochemical analysis and RT-PCR analysis of the mismatch repair genes MSH2, MSH3, MSH6, PMS1, PMS2 and MLH1. A >7-fold relative increase in mutation frequency was observed for T24 compared to a bladder cancer cell line with a fully functional mismatch repair system. Neither microsatellite instability, loss of repair nor mismatch repair gene mutations were detected. However, RT-PCR analysis of mRNA levels did detect changes in the ratio of expression of the Mut S and Mut L homologues. The T24 cell line had the lowest MSH6 expression level of the cell lines tested. Identical RT-PCR analysis of seventeen clinical samples (normal urothelium, 7; pTa low stage, 5; and pT1-4 high stage, 5) indicated a significant change in the expression ratio between MSH3/MSH6 (P< 0.004), MSH2/MSH3 (P< 0.012) and PMS2/MLH1 P< 0.005, in high stage bladder tumours compared to normal urothelium and low stage tumours. Collectively, the data suggest that imbalanced expression of mismatch repair genes could lead to partial loss of mismatch repair activity that is associated with invasive bladder cancer. © 2001 Cancer Research Campaign http://www.bjcancer.co

Orbits of Globular Clusters in the Outer Galaxy: NGC 7006

We present a proper motion study of the distant globular cluster NGC 7006 based on the measurement of 25 photographic plates spanning a 40-year interval. The absolute proper motion determined with respect to extragalactic objects is (-0.96, -1.14) +- (0.35, 0.40) mas/yr. The total space velocity of NGC 7006 in a Galactocentric rest frame is 279 km/s, placing the cluster on one of the most energetic orbits (Ra =102 kpc) known to date for clusters within 40-kpc from the Galactic center. We compare the orbits of four clusters that have apocentric radii larger than 80 kpc (NGC 5466, NGC 6934, NGC 7006 and Pal 13) with those of Galactic satellites with well-measured proper motions. These clusters have orbits that are highly eccentric and of various inclinations with respect to the Galactic plane. In contrast, the orbits of the Galactic satellites are of low to moderate eccentricity and highly inclined. Based on orbit types, chemical abundances and cluster parameters, we discuss the properties of the hypothetical host systems of the remote globular clusters in the Searle-Zinn paradigm. It is apparent that clusters such as NGC 5466, NGC 6934 and NGC 7006 formed in systems that more likely resemble the Fornax dSph, rather than the Sagittarius dSph. We also discuss plausible causes for the difference found so far between the orbit type of outer halo clusters and that of Galactic satellites and for the tentative, yet suggestive phase-space scatter found among outer halo clusters.Comment: 27 pages, 5 figures, to be published in the Astronomical Journa

Progressive multifocal leukoencephalopathy in a multiple Sclerosis patient diagnosed after switching from natalizumab to fingolimod

Background: Natalizumab- (NTZ-) associated progressive multifocal leukoencephalopathy (PML) is a severe and often disabling infectious central nervous system disease that can become evident in multiple sclerosis (MS) patients after NTZ discontinuation. Recently, novel diagnostic biomarkers for the assessment of PML risk in NTZ treated MS patients such as the anti-JC virus antibody index have been reported, and the clinical relevance of milky-way lesions detectable by MRI has been discussed. Case Presentation and Conclusion: We report a MS patient in whom PML was highly suspected solely based on MRI findings after switching from NTZ to fingolimod despite repeatedly negative (ultrasensitive) polymerase chain reaction (PCR) testing for JC virus DNA in cerebrospinal fluid. The PML diagnosis was histopathologically confirmed by brain biopsy. The occurrence of an immune reconstitution inflammatory syndrome (IRIS) during fingolimod therapy, elevated measures of JCV antibody indices, and the relevance of milky-way-like lesions detectable by (7 T) MRI are discussed

Detection of mutations in the dystrophin gene via automated DHPLC screening and direct sequencing

BACKGROUND: Currently molecular diagnostic laboratories focus only on the identification of large deletion and duplication mutations (spanning one exon or more) for Duchenne Muscular Dystrophy (DMD) yielding 65% of causative mutations. These mutations are detected by an existing set of multiplexed polymerase chain reaction (PCR) primer pairs. Due to the large size of the dystrophin gene (79 exons), finding point mutations (substitutions, deletions or insertions of one or several nucleotides) has been prohibitively expensive and laborious. The aim of this project was to develop an effective and convenient method of finding all, or most, mutations in the dystrophin gene with only a moderate increase in cost. RESULTS: Using denaturing high performance liquid chromatography (DHPLC) screening and direct sequencing, 86 PCR amplicons of genomic DNA from the dystrophin gene were screened for mutations in eight patients diagnosed with DMD who had tested negative for large DNA rearragements. Mutations likely to be disease-causative were found in six of the eight patients. All 86 amplicons from the two patients in whom no likely disease-causative mutations were found were completely sequenced and only polymorphisms were found. CONCLUSIONS: We have shown that it is now feasible for clinical laboratories to begin testing for both point mutations and large deletions/duplications in the dystrophin gene. The detection rate will rise from 65% to greater than 92% with only a moderate increase in cost

Sex chromosome positions in human interphase nuclei as studied by in situ hybridization with chromosome specific DNA probes

Two cloned repetitive DNA probes, pXBR and CY1, which bind preferentially to specific regions of the human X and Y chromosome, respectively, were used to study the distribution of the sex chromosomes in human lymphocyte nuclei by in situ hybridization experiments. Our data indicate a large variability of the distances between the sex chromosomes in male and female interphase nuclei. However, the mean distance observed between the X and Y chromosome was significantly smaller than the mean distance observed between the two X-chromosomes. The distribution of distances determined experimentally is compared with three model distributions of distances, and the question of a non-random distribution of sex chromosomes is discussed. Mathematical details of these model distributions are provided in an Appendix to this paper. In the case of a human translocation chromosome (XqterXp22.2::Yq11Y qter) contained in the Chinese hamster x human hybrid cell line 445 x 393, the binding sites of pXBR and CY1 were found close to each other in most interphase nuclei. These data demonstrate the potential use of chromosome-specific repetitive DNA probes to study the problem of interphase chromosome topography

Exploring Halo Substructure with Giant Stars. VI. Extended Distributions of Giant Stars Around the Carina Dwarf Spheroidal Galaxy -- How Reliable Are They?

The question of the existence of active tidal disruption around various dSph galaxies remains controversial. That debate often centers on the nature (bound vs. unbound) of extended populations of stars. However, the more fundamental issue of the very existence of the extended populations is still contentious. We present an evaluation of the debate centering on one particular dSph, Carina, for which claims both for and against the existence of stars beyond the King radius have been made. Our review includes an examination of all previous studies bearing on the Carina radial profile and shows that the survey method which achieves the highest detected dSph signal-to-background in the outer parts of the galaxy is the Washington M, T2 + DDO51 (MTD) filter approach from Paper II in this series. We then address statistical methods used to evaluate the reliability of MTD surveys in the presence of photometric errors and for which a new, a posteriori statistical analysis methodology is provided. Finally, these statistical methods are tested by new spectroscopy of stars in the MTD-selected Carina candidate sample. Of 74 candidate giants with follow-up spectroscopy, the MTD technique identified 61 new Carina members, including 8 stars outside the King radius. From a sample of 29 stars not initially identified as candidate Carina giants but that lie just outside of our selection criteria, 12 have radial velocities consistent with membership, including 5 extratidal stars. Carina is shown to have an extended population of giant stars extending to a major axis radius of 40' (1.44x the nominal King radius).Comment: 56 pages, 10 figures. Submitted to the Astronomical Journal, 2004 Sep 2

Chromosome assignment of two cloned DNA probes hybridizing predominantly to human sex chromosomes

In situ hybridization experiments were carried out with two clones, YACG 35 and 2.8, which had been selected from two genomic libraries strongly enriched for the human Y chromosome. Besides the human Y chromosome, both sequences strongly hybridized to the human X chromosome, with few minor binding sites on autosomes. In particular, on the X chromosome DNA from clone YACG 35 hybridized to the centromeric region and the distal part of the short arm (Xp2.2). On the Y chromosome, the sequence was assigned to one site situated in the border region between Yq1.1 and Yq1.2. DNA from clone 2.8 also hybridized to the centromeric region of the X and the distal part of the short arm (Xq2.2). On the Y, however, two binding sites were observed (Yp1.1 and Yq1.2). The findings indicate that sex chromosomal sequences may be localized in homologous regions (as suggested from meiotic pairing) but also at ectopic sites

Chapter 8: Droughts, Floods, and Wildfires

Recent droughts and associated heat waves have reached record intensity in some regions of the United States; however, by geographical scale and duration, the Dust Bowl era of the 1930s remains the benchmark drought and extreme heat event in the historical record (very high confidence). While by some measures drought has decreased over much of the continental United States in association with long-term increases in precipitation, neither the precipitation increases nor inferred drought decreases have been confidently attributed to anthropogenic forcing. The human effect on recent major U.S. droughts is complicated. Little evidence is found for a human influence on observed precipitation deficits, but much evidence is found for a human influence on surface soil moisture deficits due to increased evapotranspiration caused by higher temperatures. Future decreases in surface (top 10 cm) soil moisture from anthropogenic forcing over most of the United States are likely as the climate warms under higher scenarios. Substantial reductions in western U.S. winter and spring snowpack are projected as the climate warms. Earlier spring melt and reduced snow water equivalent have been formally attributed to human-induced warming (high confidence) and will very likely be exacerbated as the climate continues to warm (very high confidence). Under higher scenarios, and assuming no change to current water resources management, chronic, long-duration hydrological drought is increasingly possible by the end of this century. Detectable changes in some classes of flood frequency have occurred in parts of the United States and are a mix of increases and decreases. Extreme precipitation, one of the controlling factors in flood statistics, is observed to have generally increased and is projected to continue to do so across the United States in a warming atmosphere. However, formal attribution approaches have not established a significant connection of increased riverine flooding to human-induced climate change, and the timing of any emergence of a future detectable anthropogenic change in flooding is unclear. The incidence of large forest fires in the western United States and Alaska has increased since the early 1980s and is projected to further increase in those regions as the climate warms, with profound changes to certain ecosystems