387 research outputs found
DESORPTION YIELDS USING keV POLYATOMIC PROJECTILES
We have studied the negative secondary ion emission from solid organic targets bombarded by molecular ions and cluster ions. As an example we present here the results obtained with the compound phenylalanine. We have used organic projectiles of mass 73 [Si (CH3)+], 147[Si(CH3)3 OSi(CH3)2+], 300 [molecular ion of coronene C24H12]+, 598 [coronene dimer 2(M-H)]+, and atomic and polyatomic ions of mass 133 [Cs]+, 393 [Cs2I]+, 653 [Cs3I2]+. These primary ions have been produced in the bombardment of targets of coronene and CsI by fission fragment from a 252Cf source. They were accelerated and focussed on the sample target. Sophisticated time of flight measurements of the primary and secondary ions have been performed with a special data acquisition system. All the time of flight mass spectra were recorded at one. The secondary molecular ion yield of the phenilalanine (M-H)- = 164 has been studied as a function of the energy of impact and of the mass of the projectile. A large enhancement of the yield with the mass and the energy is observed
Groundwater fauna in an urban area: natural or affected?
In Germany, 70 % of the drinking water demand is met by groundwater, for which the quality is the product of multiple physical–chemical and biological processes. As healthy groundwater ecosystems help to provide clean drinking water, it is necessary to assess their ecological conditions. This is particularly true for densely populated urban areas, where faunistic groundwater investigations are still scarce. The aim of this study is, therefore, to provide a first assessment of the groundwater fauna in an urban area. Thus, we examine the ecological status of an anthropogenically influenced aquifer by analysing fauna in 39 groundwater monitoring wells in the city of Karlsruhe (Germany). For classification, we apply the groundwater ecosystem status index (GESI), in which a threshold of more than 70 % of crustaceans and less than 20 % of oligochaetes serves as an indication for very good and good ecological conditions. Our study reveals that only 35 % of the wells in the residential, commercial and industrial areas and 50 % of wells in the forested area fulfil these criteria. However, the study did not find clear spatial patterns with respect to land use and other anthropogenic impacts, in particular with respect to groundwater temperature. Nevertheless, there are noticeable differences in the spatial distribution of species in combination with abiotic groundwater characteristics in groundwater of the different areas of the city, which indicate that a more comprehensive assessment is required to evaluate the groundwater ecological status in more detail. In particular, more indicators, such as groundwater temperature, indicator species, delineation of site-specific characteristics and natural reference conditions should be considered
Transcript quantification with RNA-Seq data
Motivation Novel high-throughput sequencing technologies open exciting new approaches to transcriptome profiling. Sequencing transcript populations of interest, e.g. from different tissues or variable stress conditions, with RNA sequencing (RNA-Seq) [1] generates millions of short reads. Accurately aligned to a reference genome, they provide digital counts and thus facilitate transcript quantification. As the observed read counts only provide the summation of all expressed sequences at one locus, the inference of the underlying transcript abundances is crucial for further quantitative analyses. Methods To approach this problem, we have developed a new technique, called rQuant, based on quadratic programming. Given a gene annotation and position-wise exon/intron read coverage from read alignments, we determine the abundances for each annotated transcript by minimising a suitable loss function. It penalises the deviation of the observed from the expected read coverage given the transcript weights. The observed read coverage is typically non-uniformly distributed over the transcript due to several biases in the generation of the sequencing libraries and the sequencing. This leads to distortions of the transcript abundances, if not corrected properly. We therefore extended our approach to jointly optimise transcript profiles, modeling the coverage deviations depending on the position in the transcript. Our method can be applied without knowledge of the underlying transcript abundances and equally benefits from loci with and without alternative transcripts. Results To quantitatively evaluate the quality of our abundance predictions, we used a set of simulated reads from transcripts with known expression as a benchmark set. It was generated using the Flux Simulator [2] modeling biases in RNA-Seq as well as preparation experiments. Table 1 shows preliminary results with segment- and position-based loss as well as with and without the transcript profiles. Our results indicate that the position-based modeling together with transcript profiles allows us to accurately infer the underlying expression of single transcripts as well as of multiple isoforms of one gene locus
Reproducing Kernels of Generalized Sobolev Spaces via a Green Function Approach with Distributional Operators
In this paper we introduce a generalized Sobolev space by defining a
semi-inner product formulated in terms of a vector distributional operator
consisting of finitely or countably many distributional operators
, which are defined on the dual space of the Schwartz space. The types of
operators we consider include not only differential operators, but also more
general distributional operators such as pseudo-differential operators. We
deduce that a certain appropriate full-space Green function with respect to
now becomes a conditionally positive
definite function. In order to support this claim we ensure that the
distributional adjoint operator of is
well-defined in the distributional sense. Under sufficient conditions, the
native space (reproducing-kernel Hilbert space) associated with the Green
function can be isometrically embedded into or even be isometrically
equivalent to a generalized Sobolev space. As an application, we take linear
combinations of translates of the Green function with possibly added polynomial
terms and construct a multivariate minimum-norm interpolant to data
values sampled from an unknown generalized Sobolev function at data sites
located in some set . We provide several examples, such
as Mat\'ern kernels or Gaussian kernels, that illustrate how many
reproducing-kernel Hilbert spaces of well-known reproducing kernels are
isometrically equivalent to a generalized Sobolev space. These examples further
illustrate how we can rescale the Sobolev spaces by the vector distributional
operator . Introducing the notion of scale as part of the
definition of a generalized Sobolev space may help us to choose the "best"
kernel function for kernel-based approximation methods.Comment: Update version of the publish at Num. Math. closed to Qi Ye's Ph.D.
thesis (\url{http://mypages.iit.edu/~qye3/PhdThesis-2012-AMS-QiYe-IIT.pdf}
Smoking and health-related quality of life in English general population: Implications for economic evaluations
Copyright @ 2012 Vogl et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Little is known as to how health-related quality of life (HRQoL) when measured by generic instruments such as EQ-5D differ across smokers, ex-smokers and never-smokers in the general population; whether the overall pattern of this difference remain consistent in each domain of HRQoL; and what implications this variation, if any, would have for economic evaluations of tobacco control interventions. Methods: Using the 2006 round of Health Survey for England data (n = 13,241), this paper aims to examine the impact of smoking status on health-related quality of life in English population. Depending upon the nature of the EQ-5D data (i.e. tariff or domains), linear or logistic regression models were fitted to control for biology, clinical conditions, socio-economic background and lifestyle factors that an individual may have regardless of their smoking status. Age- and gender-specific predicted values according to smoking status are offered as the potential 'utility' values to be used in future economic evaluation models. Results: The observed difference of 0.1100 in EQ-5D scores between never-smokers (0.8839) and heavy-smokers (0.7739) reduced to 0.0516 after adjusting for biological, clinical, lifestyle and socioeconomic conditions. Heavy-smokers, when compared with never-smokers, were significantly more likely to report some/severe problems in all five domains - mobility (67%), self-care (70%), usual activity (42%), pain/discomfort (46%) and anxiety/depression (86%) -. 'Utility' values by age and gender for each category of smoking are provided to be used in the future economic evaluations. Conclusion: Smoking is significantly and negatively associated with health-related quality of life in English general population and the magnitude of this association is determined by the number of cigarettes smoked. The varying degree of this association, captured through instruments such as EQ-5D, may need to be fed into the design of future economic evaluations where the intervention being evaluated affects (e.g. tobacco control) or is affected (e.g. treatment for lung cancer) by individual's (or patients') smoking status
Androgen receptor abnormalities
The human androgen receptor is a member of the superfamily of steroid hormone receptors. Proper functioning of this protein is a prerequisite for normal male sexual differentiation and development. The cloning of the human androgen receptor cDNA and the elucidation of the genomic organization of the corresponding gene has enabled us to study androgen receptors in subjects with the clinical manifestation of androgen insensitivity and in a human prostate carcinoma cell line (LNCaP). Using PCR amplification, subcloning and sequencing of exons 2–8, we identified a G → T mutation in the androgen receptor gene of a subject with the complete form of androgen insensitivity, which inactivates the splice donor site at the exon 4/intron 4 boundary. This mutation causes the inactivation of a cryptic splice donor site in exon 4, which results in the deletion of 41 amino acids from the steroid binding domain. In two other independently arising cases we identified two different nucleotide alterations in codon 686 (GAC; aspartic acid) located in exon 4. One mutation (G → C) results in an aspartic acid → histidine substitution (with negligible androgen binding), whereas the other mutation (G → A) leads to an aspartic acid → asparagine substitution (normal androgen binding, but a rapidly dissociating androgen receptor complex). Sequence analysis of the androgen receptor in human LNCaP-cells (lymph node carcinoma of the prostate) revealed a point mutation (A → G) in codon 868 in exon 8 resulting in the substitution of threonine by alanine. This mutation is the cause of the altered steroid binding specificity of the LNCaP-cell androgen receptor. The functional consequences of the observed mutations with respect to protein expression, specific ligand binding and transcriptional activation, were established after transient expression of the mutant receptors in COS and HeLa cells. These findings illustrate that functional error
Adiposity has differing associations with incident coronary heart disease and mortality in the Scottish population: cross-sectional surveys with follow-up
Objective:
Investigation of the association of excess adiposity with three different outcomes: all-cause mortality, coronary heart disease (CHD) mortality and incident CHD.
Design:
Cross-sectional surveys linked to hospital admissions and death records.
Subjects:
19 329 adults (aged 18–86 years) from a representative sample of the Scottish population.
Measurements:
Gender-stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality, CHD mortality and incident CHD. Separate models incorporating the anthropometric measurements body mass index (BMI), waist circumference (WC) or waist–hip ratio (WHR) were created adjusted for age, year of survey, smoking status and alcohol consumption.
Results:
For both genders, BMI-defined obesity (greater than or equal to30 kg m−2) was not associated with either an increased risk of all-cause mortality or CHD mortality. However, there was an increased risk of incident CHD among the obese men (hazard ratio (HR)=1.78; 95% confidence interval=1.37–2.31) and obese women (HR=1.93; 95% confidence interval=1.44–2.59). There was a similar pattern for WC with regard to the three outcomes; for incident CHD, the HR=1.70 (1.35–2.14) for men and 1.71 (1.28–2.29) for women in the highest WC category (men greater than or equal to102 cm, women greater than or equal to88 cm), synonymous with abdominal obesity. For men, the highest category of WHR (greater than or equal to1.0) was associated with an increased risk of all-cause mortality (1.29; 1.04–1.60) and incident CHD (1.55; 1.19–2.01). Among women with a high WHR (greater than or equal to0.85) there was an increased risk of all outcomes: all-cause mortality (1.56; 1.26–1.94), CHD mortality (2.49; 1.36–4.56) and incident CHD (1.76; 1.31–2.38).
Conclusions:
In this study excess adiposity was associated with an increased risk of incident CHD but not necessarily death. One possibility is that modern medical intervention has contributed to improved survival of first CHD events. The future health burden of increased obesity levels may manifest as an increase in the prevalence of individuals living with CHD and its consequences
Variation of health-related quality of life assessed by caregivers and patients affected by severe childhood infections.
BACKGROUND: The agreement between self-reported and proxy measures of health status in ill children is not well established. This study aimed to quantify the variation in health-related quality of life (HRQOL) derived from young patients and their carers using different instruments. METHODS: A hospital-based cross-sectional survey was conducted between August 2010 and March 2011. Children with meningitis, bacteremia, pneumonia, acute otitis media, hearing loss, chronic lung disease, epilepsy, mild mental retardation, severe mental retardation, and mental retardation combined with epilepsy, aged between five to 14 years in seven tertiary hospitals were selected for participation in this study. The Health Utilities Index Mark 2 (HUI2), and Mark 3 (HUI3), and the EuroQoL Descriptive System (EQ-5D) and Visual Analogue Scale (EQ-VAS) were applied to both paediatric patients (self-assessment) and caregivers (proxy-assessment). RESULTS: The EQ-5D scores were lowest for acute conditions such as meningitis, bacteremia, and pneumonia, whereas the HUI3 scores were lowest for most chronic conditions such as hearing loss and severe mental retardation. Comparing patient and proxy scores (n = 74), the EQ-5D exhibited high correlation (r = 0.77) while in the HUI2 and HUI3 patient and caregiver scores were moderately correlated (r = 0.58 and 0.67 respectively). The mean difference between self and proxy-assessment using the HUI2, HUI3, EQ-5D and EQ-VAS scores were 0.03, 0.05, -0.03 and -0.02, respectively. In hearing-impaired and chronic lung patients the self-rated HRQOL differed significantly from their caregivers. CONCLUSIONS: The use of caregivers as proxies for measuring HRQOL in young patients affected by pneumococcal infection and its sequelae should be employed with caution. Given the high correlation between instruments, each of the HRQOL instruments appears acceptable apart from the EQ-VAS which exhibited low correlation with the others
Requirement of DNMT1 to orchestrate epigenomic reprogramming for NPM-ALK-driven lymphomagenesis
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