Continuous MLL-ENL expression is necessary to establish a "Hox Code" and maintain immortalization of hematopoietic progenitor cells

The t[(11;19)(p22;q23)] translocation, which gives rise to the MLL-ENL fusion protein, is commonly found in infant acute leukemias of both the myeloid and lymphoid lineage. To investigate the molecular mechanism of immortalization by MLL-ENL we established a Tet-regulatable system of MLL-ENL expression in primary hematopoietic progenitor cells. Immortalized myeloid cell lines were generated, which are dependent on continued MLL-ENL expression for their survival and proliferation. These cells either terminally differentiate or die when MLL-ENL expression is turned off with doxycycline. The expression profile of all 39 murine Hox genes was analyzed in these cells by real-time quantitative PCR. This analysis showed that loss of MLL-ENL was accompanied by a reduction in the expression of multiple Hoxa genes. By comparing these changes with Hox gene expression in cells induced to differentiate with granulocyte colony-stimulating factor, we show for the first time that reduced Hox gene expression is specific to loss of MLL-ENL and is not a consequence of differentiation. Our data also suggest that the Hox cofactor Meis-2 can substitute for Meis-1 function. Thus, MLL-ENL is required to initiate and maintain immortalization of myeloid progenitors and may contribute to leukemogenesis by aberrantly sustaining the expression of a "Hox code" consisting of Hoxa4 to Hoxa11.

Damping torque analysis for DC bus implemented damping control

Damping torque analysis is a well-developed technique for understanding and studying power system oscillations. This paper presents the applications of damping torque analysis for DC bus implemented damping control in power transmission networks in two examples. The first example is the investigation of damping effect of shunt VSC (Voltage Source Converter) based FACTS voltage control, i.e., STATCOM (Static Synchronous Compensator) voltage control. It is shown in the paper that STATCOM voltage control mainly contributes synchronous torque and hence has little effect on the damping of power system oscillations. The second example is the damping control implemented by a Battery Energy Storage System (BESS) installed in a power system. Damping torque analysis reveals that when BESS damping control is realized by regulating exchange of active and reactive power between the BESS and power system respectively, BESS damping control exhibits different properties. It is concluded by damping torque analysis that BESS damping control implemented by regulating active power is better with less interaction with BESS voltage control and more robust to variations of power system operating conditions. In the paper, all analytical conclusions obtained are demonstrated by simulation results of example power systems.

Probabilistic program analysis for parallelizing compilers

Parallelizing compilers have difficulty analysing and optimising complex code. To address this, some analysis may be delayed until run-time, and techniques such as speculative execution used. Furthermore, to enhance performance, a feedback loop may be setup between the compile time and run-time analysis systems, as in iterative compilation. To extend this, it is proposed that the run-time analysis collects information about the values of variables not already determined, and estimates a probability measure for the sampled values. These measures may be used to guide optimisations in further analyses of the program. To address the problem of variables with measures as values, this paper also presents an outline of a novel combination of previous probabilistic denotational semantics models, applied to a simple imperative language.

MISEP method for postnonlinear blind source separation

In this letter, a standard postnonlinear blind source separation algorithm is proposed, based on the MISEP method, which is widely used in linear and nonlinear independent component analysis. To best suit a wide class of postnonlinear mixtures, we adapt the MISEP method to incorporate a priori information of the mixtures. In particular, a group of three-layered perceptrons and a linear network are used as the unmixing system to separate sources in the postnonlinear mixtures, and another group of three-layered perceptron is used as the auxiliary network. The learning algorithm for the unmixing system is then obtained by maximizing the output entropy of the auxiliary network. The proposed method is applied to postnonlinear blind source separation of both simulation signals and real speech signals, and the experimental results demonstrate its effectiveness and efficiency in comparison with existing methods.

Testing the reliability of the JEOL FEGSEM 6500F electron microprobe for quantitative major element analysis of glass shards from rhyolitic tephra.

Electronprobe microanalysis is now widely adopted in tephra studies as a technique for determining the major element geochemistry of individual glass shards. Accurate geochemical characterization is crucial for enabling robust tephra-based correlations; such information may also be used to link the tephra to a specific source and often to a particular eruption. In this article, we present major element analyses for rhyolitic natural glass standards analysed on three different microprobes and the new JEOL FEGSEM 6500F microprobe at Queen’s University Belfast. Despite the scatter in some elements, good comparability is demonstrated among data yielded from this new system, the previous Belfast JEOL-733 Superprobe, the JEOL-8200 Superprobe (Copenhagen) and the existing long-established microprobe facility in Edinburgh. Importantly, our results show that major elements analysed using different microprobes and variable operating conditions allow two high-silica glasses to be discriminated accurately.

A three-position spectral line survey of sagittarius B2 between 218 and 263 GHz. II. Data analysis

We present an analysis of the data from our Swedish-ESO Submillimetre Telescope molecular line survey in the 1.3 mm band of the N, M, and NW positions in the Sgr B2 molecular cloud. The line emissions from 42 molecular species, and some of their isotopomers, were analyzed assuming a single temperature and a homogeneous source. In cases where a source size much smaller than the antenna beam (23

Comparative analysis of synovial fluid and plasma proteomes in juvenile arthritis - Proteomic patterns of joint inflammation in early stage disease

Synovial fluid is a potential source of novel biomarkers for many arthritic disorders involving joint inflammation, including juvenile idiopathic arthritis. We first compared the distinctive protein ‘fingerprints’ of local inflammation in synovial fluid with systemic profiles within matched plasma samples. The synovial fluid proteome at the time of joint inflammation was then evaluated across clinical subgroups to identify early disease associated proteins. We measured the synovial fluid and plasma proteomes using the two-dimensional fluorescence difference gel electrophoresis approach. Image analysis software was used to highlight the expression levels of joint and subgroup associated proteins across the study cohort (n = 32). A defined subset of 30 proteins had statistically significant differences (p < 0.05) between sample types such that synovial fluid could be differentiated from plasma. Furthermore distinctive synovial proteome expression patterns segregate patient subgroups. Protein expression patterns localized in the chronically inflamed joint therefore have the potential to identify patients more likely to suffer disease which will spread from a single joint to multiple joints. The proteins identified could act as criteria to prevent disease extension by more aggressive therapeutic intervention directed at an earlier stage than is currently possible.

Disparities in breast cancer mortality trends between 30 European countries: Retrospective trend analysis of WHO mortality database

Objective: To examine changes in temporal trends in breast cancer mortality in women living in 30 European countries.
Design: Retrospective trend analysis.
Data source: WHO mortality database on causes of deaths
Subjects reviewed: Female deaths from breast cancer from 1989 to 2006
Main outcome measures: Changes in breast cancer mortality for all women and by age group (<50, 50-69, and >= 70 years) calculated from linear regressions of log transformed, age adjusted death rates. Joinpoint analysis was used to identify the year when trends in all age mortality began to change.
Results: From 1989 to 2006, there was a median reduction in breast cancer mortality of 19%, ranging from a 45% reduction in Iceland to a 17% increase in Romania. Breast cancer mortality decreased by >= 20% in 15 countries, and the reduction tended to be greater in countries with higher mortality in 1987-9. England and Wales, Northern Ireland, and Scotland had the second, third, and fourth largest decreases of 35%, 29%, and 30%, respectively. In France, Finland, and Sweden, mortality decreased by 11%, 12%, and 16%, respectively. In central European countries mortality did not decline or even increased during the period. Downward mortality trends usually started between 1988 and 1996, and the persistent reduction from 1999 to 2006 indicates that these trends may continue. The median changes in the age groups were -37% (range -76% to -14%) in women aged <50, -21% (-40% to 14%) in 50-69 year olds, and -2% (-42% to 80%) in >= 70 year olds.
Conclusions: Changes in breast cancer mortality after 1988 varied widely between European countries, and the UK is among the countries with the largest reductions. Women aged <50 years showed the greatest reductions in mortality, also in countries where screening at that age is uncommon. The increasing mortality in some central European countries reflects avoidable mortality.

Use of weaning protocols for reducing duration of mechanical ventilation in critically ill adult patients: Cochrane systematic review and meta-analysis.

Objective To investigate the effects of weaning protocols on the total duration of mechanical ventilation, mortality, adverse events, quality of life, weaning duration, and length of stay in the intensive care unit and hospital.

Design Systematic review.

Data sources Cochrane Central Register of Controlled Trials, Medline, Embase, CINAHL, LILACS, ISI Web of Science, ISI Conference Proceedings, Cambridge Scientific Abstracts, and reference lists of articles. We did not apply language restrictions.

Review methods We included randomised and quasi-randomised controlled trials of weaning from mechanical ventilation with and without protocols in critically ill adults.

Data selection Three authors independently assessed trial quality and extracted data. A priori subgroup and sensitivity analyses were performed. We contacted study authors for additional information.

Results Eleven trials that included 1971 patients met the inclusion criteria. Compared with usual care, the geometric mean duration of mechanical ventilation in the weaning protocol group was reduced by 25% (95% confidence interval 9% to 39%, P=0.006; 10 trials); the duration of weaning was reduced by 78% (31% to 93%, P=0.009; six trials); and stay in the intensive care unit length by 10% (2% to 19%, P=0.02; eight trials). There was significant heterogeneity among studies for total duration of mechanical ventilation (I(2)=76%, P

Conclusion There is evidence of a reduction in the duration of mechanical ventilation, weaning, and stay in the intensive care unit when standardised weaning protocols are used, but there is significant heterogeneity among studies and an insufficient number of studies to investigate the source of this heterogeneity. Some studies suggest that organisational context could influence outcomes, but this could not be evaluated as it was outside the scope of this review.

Exploring the adoption and implementation of discrete and integrated IT systems: A Framework for analysis

Despite the substantial organisational benefits of integrated IT, the implementation of such systems – and particularly Enterprise Resource Planning (ERP) systems – has tended to be problematic, stimulating an extensive body of research into ERP implementation. This research has remained largely separate from the main IT implementation literature. At the same time, studies of IT implementation have generally adopted either a factor or process approach; both have major limitations. To address these imitations, factor and process perspectives are combined here in a unique model of IT implementation. We argue that • the organisational factors which determine successful implementation differ for integrated and traditional, discrete IT • failure to manage these differences is a major source of integrated IT failure. The factor/process model is used as a framework for proposing differences between discrete and integrated IT.

Framework for Establishing Limits of Tabular Aerodynamic Models for Flight Dynamics Analysis

This paper describes the use of the Euler equations for the generation and testing of tabular aerodynamic models for flight dynamics analysis. Maneuvers for the AGARD Standard Dynamics Model sharp leading-edge wind-tunnel geometry are considered as a test case. Wind-tunnel data is first used to validate the prediction of static and dynamic coefficients at both low and high angles, featuring complex vortical flow, with good agreement obtained at low to moderate angles of attack. Then the generation of aerodynamic tables is described based on a data fusion approach. Time-optimal maneuvers are generated based on these tables, including level flight trim, pull-ups at constant and varying incidence, and level and 90 degrees turns. The maneuver definition includes the aircraft states and also the control deflections to achieve the motion. The main point of the paper is then to assess the validity of the aerodynamic tables which were used to define the maneuvers. This is done by replaying them, including the control surface motions, through the time accurate computational fluid dynamics code. The resulting forces and moments are compared with the tabular values to assess the presence of inadequately modeled dynamic or unsteady effects. The agreement between the tables and the replay is demonstrated for slow maneuvers. Increasing rate maneuvers show discrepancies which are ascribed to vortical flow hysteresis at the higher rate motions. The framework is suitable for application to more complex viscous flow models, and is powerful for the assessment of the validity of aerodynamics models of the type currently used for studies of flight dynamics.

Analysis of luminescent samples using subtracted shifted Raman spectroscopy

A novel method of obtaining high-quality Raman spectra of luminescent samples was tested using cyclohexane solutions which had been treated with a fluorescent dye. The method involves removing the fixed pattern irregularity found in the spectra taken with CCD detectors by subtracting spectra taken at several different, closely spaced spectrometer positions. It is conceptually similar to SERDS (shifted excitation Raman difference spectroscopy) but has the distinct experimental advantage that it does not require a tunable laser source. The subtracted spectra obtained as the raw data are converted into a more recognisable and conventional form by iterative fitting of appropriate double Lorentzian functions whose peak parameters are then used to 'reconstruct' a conventional representation of the spectrum. Importantly, it is shown that the degree of uncertainty in the resultant 'reconstructed' spectra can be gauged reliably by comparing reconstructed spectra obtained at two different spectrometer shifts (delta and 2 delta), The method was illustrated and validated using a solvent (cyclohexane) the spectrum of which is well known and which contains both regions with complex overlapping bands and regions with isolated bands, Possible sources of error are discussed and it is shown that, provided the degree of uncertainty in the data is correctly characterised, it is completely valid to draw conclusions about the spectra of the sample on the basis of the reconstructed data. The acronym SSRS (subtracted shifted Raman spectroscopy; pronounced scissors) is proposed for this method, to distinguish it from the SERDS technique.

Electric Vehicles - a well to wheel analysis

The European Union has set a target for 10% renewable energy in transport by 2020, which will be met using both biofuels and electric vehicles. In the case of biofuels, for the purposes of meeting the target, the biofuel must achieve greenhouse gas savings of 35% relative to the fossil fuel replaced. For biofuels, greenhouse gas savings can be calculated using life cycle analysis, or the European Union default values. In contrast, all electricity used in transport is considered to be the same, regardless of the source or the type of electric vehicle. However, the choice of the electric vehicle and electricity source will have a major impact on the greenhouse gas savings. This paper examines different electric-vehicle scenarios in terms of greenhouse gas savings, using a well-to-wheel life cycle analysis.

Dosimetry and spectral analysis of a radiobiological experiment using laser-driven proton beams

Laser-driven proton and ion acceleration is an area of increasing research interest given the recent development of short pulse-high intensity lasers. Several groups have reported experiments to understand whether a laser-driven beam can be applied for radiobiological purposes and in each of these, the method to obtain dose and spectral analysis was slightly different. The difficulty with these studies is that the very large instantaneous dose rate is a challenge for commonly used dosimetry techniques, so that other more sophisticated procedures need to be explored. This paper aims to explain a method for obtaining the energetic spectrum and the dose of a laser-driven proton beam irradiating a cell dish used for radiobiology studies. The procedure includes the use of a magnet to have charge and energy separation of the laser-driven beam, Gafchromic films to have information on dose and partially on energy, and a Monte Carlo code to expand the measured data in order to obtain specific details of the proton spectrum on the cells. Two specific correction factors have to be calculated: one to take into account the variation of the dose response of the films as a function of the proton energy and the other to obtain the dose to the cell layer starting from the dose measured on the films. This method, particularly suited to irradiation delivered in a single laser shot, can be applied in any other radiobiological experiment performed with laser-driven proton beams, with the only condition that the initial proton spectrum has to be at least roughly known. The method was tested in an experiment conducted at Queen's University of Belfast using the TARANIS laser, where the mean energy of the protons crossing the cells was between 0.9 and 5 MeV, the instantaneous dose rate was estimated to be close to 10(9) Gy s(-1) and doses between 0.8 and 5 Gy were delivered to the cells in a single laser shot. The combination of the applied corrections modified the initial estimate of dose by up to 40%.

Blue luminous stars in nearby galaxies: Quantitative spectral analysis of M33 B-type supergiant stars

We present the detailed spectral analysis of a sample of M33 B-type supergiant stars, aimed at the determination of their fundamental parameters and chemical composition. The analysis is based on a grid of non-LTE metal line-blanketed model atmospheres including the effects of stellar winds and spherical extension computed with the code FASTWIND. Surface abundance ratios of C, N, and O are used to discuss the chemical evolutionary status of each individual star. The comparison of observed stellar properties with theoretical predictions of massive star evolutionary models shows good agreement within the uncertainties of the analysis. The spatial distribution of the sample allows us to investigate the existence of radial abundance gradients in the disk of M33. The comparison of stellar and H II region O abundances ( based on direct determinations of the electron temperature of the nebulae) shows good agreement. Using a simple linear radial representation, the stellar oxygen abundances result in a gradient of -0.0145 +/- 0.005 dex arcmin(-1) (or -0.06 +/- 0.02 dex kpc(-1)) up to a distance equal to similar to 1.1 times the isophotal radius of the galaxy. A more complex representation cannot be completely discarded by our stellar sample. The stellar Mg and Si abundances follow the trend displayed by O abundances, although with shallower gradients. These differences in gradient slope cannot be explained at this point. The derived abundances of the three alpha-elements yield solar metallicity in the central regions of the disk of M33. A comparison with recent planetary nebula data from Magrini and coworkers indicates that the disk of M33 has not suffered from a significant O enrichment in the last 3 Gyr.