406 research outputs found

    Mass Fractionation and Energy Distribution of Sputtered Monatomic Positive Ions

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    Secondary ion yields in sputtering depend significantly on the mass of the emitted species. Ionization as observed by secondary ion mass spectrometry is characterized by isotope fractionation; the yield of an isotope ion of mass Mi being proportional to M-, where a varies with the emitted species, its kinetic energy Ek, and the matrix. By means of SIMS, isotope ratios have been measured for ions at energies up to ca 120 eV in different metallic matrices. For singly charged positive monatomic ions, a has been found to range between O and ca 4. While a may drop steeply at low or moderate Ek, at higher energies the gradient decreases and usually becomes positive. To some extent the trends of a are complementary to those of the energy dependence of elemental ion yields. In the present work, the main tendencies are surveyed for pure element matrices as well as for several elements sputtered from a given metallic matrix. It is attempted to correlate a with the energy distributions of ionic yields. Isotope effects appear inherent in all three basic mechanisms of ion emission, i.e., in sputter yield, ionization, and charge survival

    Impulse oscillometry may be of value in detecting early manifestations of COPD

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    SummaryBackgroundSpirometry is used to diagnose chronic obstructive pulmonary disease (COPD). The Impulse oscillometry system (IOS) allows determination of respiratory impedance indices, which might be of potential value in early COPD, although previous experience is limited. We examined pulmonary resistance and reactance measured by IOS in subjects with or without self-reported chronic bronchitis or emphysema or COPD (Q+ or Q−) and subjects with or without COPD diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (G+ or G−).MethodsFrom a previous population-based study 450 subjects were examined with spirometry and IOS and answered a questionnaire on respiratory symptoms and diseases.ResultsSeventy-seven subjects were Q+, of whom 34 also were G+. Q+/G− subjects (n = 43) reported respiratory symptoms more frequently (35–40% vs 8–14%) but had higher FEV1 (100% vs 87%) than Q−/G+ subjects (n = 90), p < 0.05 for both comparisons. Q+ subjects had higher pulmonary resistance and lower pulmonary reactance than Q− subjects (p < 0.01 for all comparisons). The same pattern was seen both in G+ subjects ((Q+/Q−) R5 0.39/0.32, R5–R20 0.10/0.07, X5 0.13/0.09, AX 0.55/0.27, p < 0.05 for all) and G− subjects ((Q+/Q−) R5 0.35/0.29, R5–R20 0.08/0.06, X5 0.10/0.08, AX 0.31/0.19 p < 0.05 for all) except for R20 (adjusted for gender and age).ConclusionsSelf-reported chronic bronchitis or emphysema or COPD was associated with higher pulmonary resistance and lower pulmonary reactance measured by IOS, both among subjects with and without COPD according to GOLD criteria. IOS may have the potential to detect pathology associated with COPD earlier than spirometry

    Tautomers of N-acetyl-d-allosamine: an NMR and computational chemistry study

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    d-Allosamine is a rare sugar in Nature but its pyranoid form has been found alpha-linked in the core region of the lipopolysaccharide from the Gram-negative bacterium Porphyromonas gingivalis and in the chitanase inhibitor allosamidin, then beta-linked and N-acetylated. In water solution the monosaccharide N-acetyl-d-allosamine (d-AllNAc) shows a significant presence of four tautomers arising from pyranoid and furanoid ring forms and anomeric configurations. The furanoid ring forms both showed (3)J(H1,H2) approximate to 4.85 Hz and to differentiate the anomeric configurations a series of chemical shift anisotropy/dipole-dipole cross-correlated relaxation NMR experiments was performed in which the alpha-anomeric form showed notable different relaxation rates for its components of the H1 doublet, thereby making it possible to elucidate the anomeric configuration of each of the furanoses. The conformational preferences of the different forms of d-AllNAc were investigated by (3)J(HH), (2)J(CH) and (3)J(CH) coupling constants from NMR experiments, molecular dynamics simulations and density functional theory calculations. The pyranose form resides in the C-4(1) conformation and the furanose ring form has the majority of its conformers located on the South-East region of the pseudorotation wheel, with a small population in the Northern hemisphere. The tautomeric equilibrium was quite sensitive to changes in temperature, where the beta-anomer of the pyranoid ring form decreased upon a temperature increase while the other forms increased

    Differential expression analysis for sequence count data

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    *Motivation:* High-throughput nucleotide sequencing provides quantitative readouts in assays for RNA expression (RNA-Seq), protein-DNA binding (ChIP-Seq) or cell counting (barcode sequencing). Statistical inference of differential signal in such data requires estimation of their variability throughout the dynamic range. When the number of replicates is small, error modelling is needed to achieve statistical power.&#xd;&#xa;&#xd;&#xa;*Results:* We propose an error model that uses the negative binomial distribution, with variance and mean linked by local regression, to model the null distribution of the count data. The method controls type-I error and provides good detection power. &#xd;&#xa;&#xd;&#xa;*Availability:* A free open-source R software package, _DESeq_, is available from the Bioconductor project and from &#x22;http://www-huber.embl.de/users/anders/DESeq&#x22;:http://www-huber.embl.de/users/anders/DESeq

    Deltagande Forskning – Lärdomar, resultat och erfarenheter från Växthusgruppens arbete 1999–2000

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    Centrum för uthålligt lantbruk (CUL) vid SLU har initierat ett pionjärarbete att få igång deltagande forskning inom lantbrukssektorn i Sverige. I denna rapport beskrivs den läro- och förändringsprocess, de framgångar och svårigheter, som en av de grupper som ingår i CUL:s satsning genomgått och mött under sitt arbete med deltagande forskning. De resultat gruppens försök och praktiska arbete lett fram till presenteras också. Rapporten är skriven av gruppens facilitator (Karin Eksvärd) efter att ha samtalat med gruppmedlemmarna enskilt och tillsammans om deltagarnas åsikter kring gruppens arbete och arbetsformer. Några av gruppdeltagarnas åsikter och uttalanden finns inlagda som citat i rapporten. Deltagarna har även haft möjlighet att kommentera rapporten under dess framtagande. Gruppens arbete har möjliggjorts genom att rådgivarna har arrangerat gruppens möten som kurser inom miljöstödsprogrammet. Det har varit ett givande och lärorikt arbete som fortsätter att öka vårt kunnande om ekologisk tomatodling, oss själva som grupp och sättet att arbeta. Vi hoppas att denna rapport skall inspirera fler lantbrukare, rådgivare och forskare att i högre grad samverka med varandra och att på detta sätt vidareutveckla svenskt lantbruk

    A high-content small molecule screen identifies sensitivity of glioblastoma stem cells to inhibition of polo-like kinase 1

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    Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults and there are few effective treatments. GBMs contain cells with molecular and cellular characteristics of neural stem cells that drive tumour growth. Here we compare responses of human glioblastoma-derived neural stem (GNS) cells and genetically normal neural stem (NS) cells to a panel of 160 small molecule kinase inhibitors. We used live-cell imaging and high content image analysis tools and identified JNJ-10198409 (J101) as an agent that induces mitotic arrest at prometaphase in GNS cells but not NS cells. Antibody microarrays and kinase profiling suggested that J101 responses are triggered by suppression of the active phosphorylated form of polo-like kinase 1 (Plk1) (phospho T210), with resultant spindle defects and arrest at prometaphase. We found that potent and specific Plk1 inhibitors already in clinical development (BI 2536, BI 6727 and GSK 461364) phenocopied J101 and were selective against GNS cells. Using a porcine brain endothelial cell blood-brain barrier model we also observed that these compounds exhibited greater blood-brain barrier permeability in vitro than J101. Our analysis of mouse mutant NS cells (INK4a/ARF(-/-), or p53(-/-)), as well as the acute genetic deletion of p53 from a conditional p53 floxed NS cell line, suggests that the sensitivity of GNS cells to BI 2536 or J101 may be explained by the lack of a p53-mediated compensatory pathway. Together these data indicate that GBM stem cells are acutely susceptible to proliferative disruption by Plk1 inhibitors and that such agents may have immediate therapeutic value

    Population-based study of diagnostic assays for Borrelia infection: comparison of purified flagella antigen assay (Ideia™, Dako Cytomation) and recombinant antigen assay (Liaison®, DiaSorin)

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    <p>Abstract</p> <p>Background</p> <p>Testing for <it>Borrelia</it>-specific IgM and IgG-antibodies are often performed on a variety of poorly defined symptoms, and isolated IgM results are a frequent finding, which results in diagnostic uncertainty and further testing. We wanted to test the hypothesis that Borrelia-specific assays using recombinant antigens perform differently from assays based on purified flagella antigen.</p> <p>Methods</p> <p>We compared the use of recombinant antigens (LIAISON<sup>® </sup>DiaSorin, Saluggia, Italy) and purified flagella antigen (IDEIA™ Borrelia, DakoCytomation, Glostrup, Denmark) in the assay for <it>Borrelia</it>-specific IgM and IgG-antibodies. The assays were tested on an unselected population of serum samples submitted from general practice. A total of 357 consecutive samples for analysis of <it>Borrelia </it>IgM and IgG antibodies. Furthermore, we analysed 540 samples for <it>Borrelia</it>-specific IgM or IgG antibodies first by the IDEIA™ and, if they were positive, the samples were further analysed using the LIAISON<sup>® </sup>assay. To verify the correctness of the patient's serological status, discrepant samples were analysed by line blots (EcoLine, Virotech).</p> <p>Results</p> <p>In the consecutive series of 357 samples, the IgM assays detected 308 negative and 3 positive samples with concordant results. Compared with the line blot, the IDEIA™ system produced 21 false-positive IgM results, whereas the LIAISON<sup>® </sup>system produced only one false-positive IgM result. The IgG assays showed 1 positive and 328 negative concordant results. The LIAISON<sup>® </sup>system produced 9 true IgG-positive samples that were not detected by the IDEIA™ system, but the former produced 4 positive IgG results that were negative by line blot.</p> <p>Conclusion</p> <p>Diagnostic assays based on flagella antigen seem to show more false-positive IgM and false-negative IgG results than assays based on recombinant antigens. The latter may reduce the number of presumably false-positive IgM results and identify more IgG-positive subjects, but this system also produces more false-positive IgG results.</p
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