Incomplete DJH rearrangements.

Analysis of Ig genes in B-cell malignancies has become an essential method in molecular diagnosis, and polymerase chain reaction (PCR) amplification of Ig heavy chain gene (IgH) rearrangements is now widely used for detection of clonality and minimal residual disease (MRD). Although several different sensitive protocols are now available for PCR analysis of IgH genes, they are frequently hampered owing to the high rate of somatic hypermutation present in multiple myeloma (MM). We recently described a new approach using incomplete DJH rearrangements as an alternative target. About 60% of MM samples contain an incomplete DJH rearrangement, 90% of them lacking on somatic mutations. This approach allows resolution of problems derived from primer mismatches, making DJH rearrangement a reliable and sensitive target for detection of clonality and MRD investigation in MM.

Quantitative mapping of aqueous microfluidic temperature with sub-degree resolution using fluorescence lifetime imaging microscopy

The use of a water-soluble, thermo-responsive polymer as a highly sensitive fluorescence-lifetime probe of microfluidic temperature is demonstrated. The fluorescence lifetime of poly(N-isopropylacrylamide) labelled with a benzofurazan fluorophore is shown to have a steep dependence on temperature around the polymer phase transition and the photophysical origin of this response is established. The use of this unusual fluorescent probe in conjunction with fluorescence lifetime imaging microscopy (FLIM) enables the spatial variation of temperature in a microfluidic device to be mapped, on the micron scale, with a resolution of less than 0.1 degrees C. This represents an increase in temperature resolution of an order of magnitude over that achieved previously by FLIM of temperature-sensitive dyes

Keratinocyte Growth-Factor Promotes Epithelial Survival and Resolution in a Human Model of Lung Injury

Rationale: Increasing epithelial repair and regeneration may hasten resolution of lung injury in patients with the Acute Respiratory Distress Syndrome (ARDS). In animal models of ARDS, Keratinocyte Growth Factor (KGF) reduces injury and increases epithelial proliferation and repair. The effect of KGF in the human alveolus is unknown.

Objectives: To test whether KGF can attenuate alveolar injury in a human model of ARDS.

Methods: Volunteers were randomized to intravenous KGF (60 μg/kg) or placebo for 3 days, before inhaling 50μg lipopolysaccharide. Six hours later, subjects underwent bronchoalveolar lavage (BAL) to quantify markers of alveolar inflammation and cell-specific injury.

Measurements and Main Results: KGF did not alter leukocyte infiltration or markers of permeability in response to LPS. KGF increased BAL concentrations of Surfactant Protein D (SP-D), MMP-9, IL-1Ra, GM-CSF and CRP. In vitro, BAL fluid from KGF-treated subjects (KGF BAL) inhibited pulmonary fibroblast proliferation, but increased alveolar epithelial proliferation. Active MMP-9 increased alveolar epithelial wound repair. Finally, BAL from the KGF pre-treated group enhanced macrophage phagocytic uptake of apoptotic epithelial cells and bacteria compared with BAL from the placebo-treated group. This effect was blocked by inhibiting activation of the GM-CSF receptor.

Conclusions: KGF treatment increases BAL SP-D, a marker of type II alveolar epithelial cell proliferation in a human model of ALI. Additionally KGF increases alveolar concentrations of the anti-inflammatory cytokine IL-1Ra, and mediators that drive epithelial repair (MMP-9) and enhance macrophage clearance of dead cells and bacteria (GM-CSF).

Secular Trends in Substance Use: The Conflict and Young People in Northern Ireland

The resolution of political conflict has led some to suggest that Northern Ireland will now face a range of social problems that have been ignored or suppressed by the Troubles. One such area is adolescent drug use. In this article, a review of a range of data sources shows that drug use, with few exceptions, has increased since the emergence of the ongoing peace process. Social and political changes and enhanced paramilitary involvement in the drugs trade appear to have somehow created an environment where drug use has flourished. In reviewing current drug policy and practice, the article highlights the lack of prevention, treatment, and harm reduction services established in Northern Ireland as a cause for concern.

Bismuth embrittlement of copper is an atomic size effect

Embrittlement by the segregation of impurity elements to grain boundaries is one of a small number of phenomena that can lead to metallurgical failure by fast fracture(1). Here we settle a question that has been debated for over a hundred years(2): how can minute traces of bismuth in copper cause this ductile metal to fail in a brittle manner? Three hypotheses for Bi embrittlement of Cu exist: two assign an electronic effect to either a strengthening(3) or weakening(4) of bonds, the third postulates a simple atomic size effect(5). Here we report first principles quantum mechanical calculations that allow us to reject the electronic hypotheses, while supporting a size effect. We show that upon segregation to the grain boundary, the large Bi atoms weaken the interatomic bonding by pushing apart the Cu atoms at the interface. The resolution of the mechanism underlying grain boundary weakening should be relevant for all cases of embrittlement by oversize impurities.

Observations of the interstellar medium in the Magellanic Bridge.

We present ultraviolet and optical spectra of DI 1388, a young star in the Magellanic Bridge, a region of gas between the Small and Large Magellanic Clouds. The data have signal-to-noise ratios of 20-45 and a spectral resolution of 6.5 km s-1. Interstellar absorption by the Magellanic Bridge at vLSR~200 km s-1 is visible in the lines of C I, C II, C II*, C IV, N I, O I, Al II, Si II, Si III, Si IV, S II, Ca II, Fe II, and Ni II. The relative gas-phase abundances of C II, N I, O I, Al II, Si II, Fe II, and Ni II with respect to S II are similar to those found in Galactic halo clouds, despite a significantly lower metallicity in the Magellanic Bridge. The higher ionization species in the cloud have a column density ratio N(C+3)/N(Si+3)~1.9, similar to that inferred for collisionally ionized Galactic cloud interfaces at temperatures ~105 K. We identify substructure in the stronger interstellar lines, with a broad component (FWHM~20 km s-1) at ~179 km s-1 and a sharp component (FWHM~11 km s-1) at 198 km s-1. The abundance analysis for these clouds indicates that the feature at 198 km s-1 consists of a low electron density, mainly neutral gas that may be associated with an interface responsible for the highly ionized gas. The 179 km s-1 cloud consists of warmer, lower density gas that is partially ionized.

HST/STIS observations of the high-velocity interstellar cloud HVC 291.2-41.2+80: a warm, mainly ionized high-velocity cloud

We present intermediate-resolution HST/STIS spectra of a high- velocity interstellar cloud ((LSR)-L-upsilon = + 80 kms(-1)) towards DI1388, a young star in the Magellanic Bridge located between the Small and Large Magellanic Clouds. The STIS data have a signal-to-noise ratio (S/N) of 20-45 and a spectral resolution of about 6.5 km s(-1) (FWHM), The high-velocity cloud absorption is observed in the lines of C II, O I, Si II, Si III, Si IV and S III. Limits can be placed on the amount of S II and Fe II absorption that is present. An analysis of the relative abundances derived from the observed species, particularly C II and O I, suggests that this high-velocity gas is warm (T-k similar to 10(3)-10(4) K) and predominantly ionized, This hypothesis is supported by the presence of absorption produced by highly ionized species, such as Si IV, This sightline also intercepts two other high-velocity clouds that produce weak absorption features at (LSR)-L-upsilon = + 113 and + 130kms(-1) in the STIS spectra.

Multiwavelength observations of the M15 intermediate-velocity cloud

We present Westerbork Synthesis Radio Telescope HI images, Lovell telescope multibeam H I wide-field mapping, William Herschel Telescope long-slit echelle Ca II observations, Wisconsin Halpha Mapper (WHAM) facility images, and IRAS ISSA 60- and 100-mum co-added images towards the intermediate- velocity cloud (IVC) at + 70 km s(-1), located in the general direction of the M15 globular cluster. When combined with previously published Arecibo data, the H I gas in the IVC is found to be clumpy, with a peak H I column density of similar to1.5 x 10(20) cm(-2), inferred volume density (assuming spherical symmetry) of similar to24 cm(-3)/D (kpc) and a maximum brightness temperature at a resolution of 81 x 14 arcsec(2) of 14 K. The major axis of this part of the IVC lies approximately parallel to the Galactic plane, as does the low- velocity H I gas and IRAS emission. The H I gas in the cloud is warm, with a minimum value of the full width at half-maximum velocity width of 5 km s(-1) corresponding to a kinetic temperature, in the absence of turbulence, of similar to540 K. From the H I data, there are indications of two-component velocity structure. Similarly, the Ca II spectra, of resolution 7 km s(-1), also show tentative evidence of velocity structure, perhaps indicative of cloudlets. Assuming that there are no unresolved narrow-velocity components, the mean values of log(10)[N(Ca II K) cm(2)] similar to 12.0 and Ca II/H I similar to2 5 x 10(-8) are typical of observations of high Galactic latitude clouds. This compares with a value of Ca II/H I>10(-6) for IVC absorption towards HD 203664, a halo star of distance 3 kpc, some 3.degrees1 from the main M15 IVC condensation. The main IVC condensation is detected by WHAM in Halpha with central local-standard-of-rest velocities of similar to60-70 km s(-1), and intensities uncorrected for Galactic extinction of up to 1.3 R, indicating that the gas is partially ionized. The FWHM values of the Halpha IVC component, at a resolution of 1degrees, exceed 30 km s(-1). This is some 10 km s(-1) larger than the corresponding H I value at a similar resolution, and indicates that the two components may not be mixed. However, the spatial and velocity coincidence of the Halpha and H I peaks in emission towards the main IVC component is qualitatively good. If the Halpha emission is caused solely by photoionization, the Lyman continuum flux towards the main IVC condensation is similar to2.7 x 10(6) photon cm(-2) s(-1). There is not a corresponding IVC Halpha detection towards the halo star HD 203664 at velocities exceeding similar to60 km s(- 1). Finally, both the 60- and 100-mum IRAS images show spatial coincidence, over a 0.675 x 0 625 deg(2) field, with both low- and intermediate-velocity H I gas (previously observed with the Arecibo telescope), indicating that the IVC may contain dust. Both the Halpha and tentative IRAS detections discriminate this IVC from high-velocity clouds, although the H I properties do not. When combined with the H I and optical results, these data point to a Galactic origin for at least parts of this IVC.

Optical spectroscopy of the M 15 intermediate velocity cloud

We present echelle spectrograph observations in the Na D lines, at resolutions of 6.2-8.5 km s(-1), for 11 stars located in the line-of-sight to the M15 intermediate velocity cloud (IVC), which has a radial velocity of similar to +70 km s(-1) in the Local Standard of Rest. This cloud is a part of IVC Complex gp. The targets range in magnitude from m(V) = 13.3-14.8. Seven of the observed stars are in the M15 globular cluster, the remaining four being field stars. Three of the observed cluster stars are located near a peak in intensity of the IVC Hi column density as observed at a resolution of similar to 1 arcmin. Intermediate velocity gas is detected in absorption towards 7 stars, with equivalent widths in NaD2 ranging from similar to0.09-0.20 Angstrom, corresponding to log(10)(N-Na cm(-2)) similar to 11.8-12.5, and Na I/H I column density ratios (neglecting the HII component) ranging from similar to(1-3) x 10(-8). Over scales ranging from 30 arcsec to 1 arcmin, the Na i column density and the Na i/H i ratio varies by upto 70 per cent and a factor of similar to 2, respectively. Combining the current sightlines with previously obtained Nai data from Kennedy et al. (1998b), the Na i/H i column density ratio over cluster sightlines varies by upto a factor of similar to 25, when using Hi data of resolution similar to 2 x 1 arcmin. One cluster star, M15 ZNG-1, was also observed in the Ca i (lambda(air) = 4226.728 Angstrom) and Ca ii (lambda(air) = 3933.663 Angstrom) lines. A column density ratio N(Ca i)/N(Ca ii) <0.03 was found, typical of values seen in the warm ionised interstellar medium. Towards this sightline, the IVC has a Nai/Ca ii column density ratio of &SIM; 0.25, similar to that observed in the local interstellar medium. Finally, we detect tentative evidence for IV absorption in Ki (?(air) = 7698:974 &ANGS) towards 3 cluster stars, which have N(K i)/N(H i) ratios of &SIM;0.5-3 x 10(-9).

Ca II K observations of QSOs in the line-of-sight to the Magellanic Bridge

We describe medium-resolution spectroscopic observations taken with the ESO Multi-Mode Instrument (EMMI) in the CaII K line (lambda air = 3933.661 angstrom) towards 7 QSOs located in the line-of-sight to the Magellanic Bridge. At a spectral resolution R =lambda/Delta lambda = 6000, five of the sightlines have a signal-to-noise ( S/N) ratio of similar to 20 or higher. Definite Ca absorption due to Bridge material is detected towards 3 objects, with probable detection towards two other sightlines. Gas-phase CaII K Bridge and Milky Way abundances or lower limits for the all sightlines are estimated by the use of Parkes 21-cm H. emission line data. These data only have a spatial resolution of 14 arcmin compared with the optical observations which have milli-arcsecond resolution. With this caveat, for the three objects with sound CaII K detections, we find that the ionic abundance of CaII K relative to HI, A = log( N( CaK)/ N( HI)) for low- velocity Galactic gas ranges from - 8.3 to - 8.8 dex, with HI column densities varying from 3- 6 x 10(20) cm(-2). For Magellanic Bridge gas, the values of A are similar to 0.5 dex higher, ranging from similar to- 7.8 to - 8.2 dex, with N( HI) = 1- 5 x 1020 cm(-2). Higher values of A correspond to lower values of N( HI), although numbers are small. For the sightline towards B 0251 - 675, the Bridge gas has two different velocities, and in only one of these is CaII tentatively detected, perhaps indicating gas of a different origin or present-day characteristics ( such as dust content), although this conclusion is uncertain and there is the possibility that one of the components could be related to the Magellanic Stream. Higher signal-to-noise CaII K data and higher resolution H. data are required to determine whether A changes with N( HI) over the Bridge and if the implied difference in the metalicity of the two Bridge components towards B 0251-675 is real.

HI observations of the high-velocity cloud in the direction of M 92

We present wide-field neutral hydrogen (H I) Lovell telescope multibeam, and Dominion Radio Astrophysical Observatory Hi synthesis observations, of the high velocity cloud (HVC) located in the general direction of the globular cluster M92. This cloud is part of the larger Complex C and lies at velocities between similar to -80 and -130 km s(-1) in the Local Standard of Rest. The Lovell telescope observations, of resolution 12 arcmin spatially and 3.0 km s(-1) in velocity, fully sampling a 3.1 degrees x 12.6 degrees RA-Dec grid, have found that this part of HVC Complex C comprises two main condensations, lying approximately north-south in declination, separated by similar to2 degrees and being parallel to the Galactic plane. At this resolution, peak values of the brightness temperature and Hi column density of similar to1.4 K and similar to5 x 10(19) cm(-2) are determined, with relatively high values of the full width half maximum velocity (FWHM) of similar to 22 km s(-1) being observed, equivalent to a gas kinetic temperature, in the absence of turbulence and geometric effects of similar to 10 000 K. Each of these properties, as well as the sizes of the clouds, are similar in the two components. The DRAO observations, towards the Northern HVC condensation, are the first high-resolution Hi spectra of Complex C. When smoothed to a resolution of 3 arcmin, they identify several Hi intensity peaks with column densities in the range 4-7 x 10(19) cm(-2). Further smoothing of these data to 6 arcmin resolution tentatively indicates that parts of the HVC consist of two velocity components, of similar brightness temperature, separated by similar to7 km s(-1) in velocity, and with FWHM velocity widths of similar to5-7 km s(-1). No IRAS 60 or 100 micron flux is associated with the M92 HVC. Cloud properties are briefly discussed and compared to previous observations of HVCs.

An investigation of Fe XV emission lines in solar flare spectra

Previously, large discrepancies have been found between theory and observation for Fe XV emission line ratios in solar flare spectra covering the 224-327 angstrom wavelength range, obtained by the Naval Research Laboratory's S082A instrument on board Skylab. These discrepancies have been attributed to either errors in the adopted atomic data or the presence of additional atomic processes not included in the modelling, such as fluorescence. However our analysis of these plus other S082A flare observations (the latter containing Fe XV transitions between 321-482 angstrom), performed using the most recent Fe XV atomic physics calculations in conjunction with a chianti synthetic flare spectrum, indicate that blending of the lines is primarily responsible for the discrepancies. As a result, most Fe XV lines cannot be employed as electron density diagnostics for solar flares, at least at the spectral resolution of S082A and similar instruments (i.e.similar to 0.1 angstrom). An exception is the intensity ratio I(3s3p P-3(2)-3p(2) P-3(1))/I(3s3p P-3(2)-3p(2) D-1(2))=I(321.8 angstrom)/I(327.0 angstrom), which appears to provide good estimates of the electron density at this spectral resolution.

X-ray emission from charge exchange of highly-charged ions in atoms and molecules

Charge exchange followed by radiative stabilization are the main processes responsible for the recent observations of X-ray emission from comets in their approach to the Sun. A new apparatus was constructed at JPL to measure, in collisions of HCIs with atoms and molecules, (a) absolute cross sections for single and multiple charge exchange, and (b) normalized X-ray emission cross sections. The ions are produced by the JPL HCI Facility and passed through a neutral-gas target cell. The product charge states are analyzed by a retarding potential difference technique. Results are made absolute by measuring target pressure, and incident and product ion currents. X-rays emitted from the product ions are detected with a Ge solid-state detector having a resolution of approximately 100 eV. X-ray astronomy has taken major steps forward with the recent launch of the high-resolution satellites Chandra and Newton. The cross sections reported herein are essential for the development of the solar wind comet interaction models inspired by these observations.

The fall of kinship - towards an epidemiological explanation

Kinship used to be described as what anthropologists do. Today, many might well say that it is what anthropologists do not do. One possible explanation is that the notion of kinship fell off anthropology's radar due to the criticisms raised by Needham and Schneider among others, which supposedly demonstrated that kinship is not a sound theoretical concept. Drawing inspiration from epidemiological approaches to cultural phenomena, this article aims to enrich this explanation. Kinship became an unattractive theoretical concept in the subculture of anthropology not simply because of problems with kinship theory per se, but also on account of fundamental changes in the very conception of anthropological knowledge and the impact of these changes on the personal identity of anthropologists.