Molecular cytogenetic analysis of formalin-fixed, paraffin-embedded solid tumors by comparative genomic hybridization after universal DNA-amplification

We present a technique which allows the detection and chromosomal localization of DNA sequence copy number changes in solid tumor genomes from frozen sections and paraffin embedded, formalin fixed specimens. Based on comparative genomic hybridization and on universal DNA amplification procedures this technique is possible even if only a few tumor cells are available. We demonstrate the feasibility of this method to visualize complete and partial chromosome gains and losses and gene amplifications In archived solid tumor samples

Image-derived input functions from dynamic O-15-water PET scans using penalised reconstruction

BACKGROUND: Quantitative positron emission tomography (PET) scans of the brain typically require arterial blood sampling but this is complicated and logistically challenging. One solution to remove the need for arterial blood sampling is the use of image-derived input functions (IDIFs). Obtaining accurate IDIFs, however, has proved to be challenging, mainly due to the limited resolution of PET. Here, we employ penalised reconstruction alongside iterative thresholding methods and simple partial volume correction methods to produce IDIFs from a single PET scan, and subsequently, compare these to blood-sampled input curves (BSIFs) as ground truth. Retrospectively we used data from sixteen subjects with two dynamic 15O-labelled water PET scans and continuous arterial blood sampling: one baseline scan and another post-administration of acetazolamide. RESULTS: IDIFs and BSIFs agreed well in terms of the area under the curve of input curves when comparing peaks, tails and peak-to-tail ratios with R2 values of 0.95, 0.70 and 0.76, respectively. Grey matter cerebral blood flow (CBF) values showed good agreement with an average difference between the BSIF and IDIF CBF values of 2% ± and a coefficient of variation (CoV) of 7.3%. CONCLUSION: Our results show promising results that a robust IDIF can be produced for dynamic 15O–water PET scans using only the dynamic PET scan images with no need for a corresponding MRI or complex analytical techniques and thereby making routine clinical use of quantitative CBF measurements with 15O–water feasible

Methane Clumped Isotopes: Progress and Potential for a New Isotopic Tracer

The isotopic composition of methane is of longstanding geochemical interest, with important implications for understanding petroleum systems, atmospheric greenhouse gas concentrations, the global carbon cycle, and life in extreme environments. Recent analytical developments focusing on multiply substituted isotopologues (‘clumped isotopes’) are opening a valuable new window into methane geochemistry. When methane forms in internal isotopic equilibrium, clumped isotopes can provide a direct record of formation temperature, making this property particularly valuable for identifying different methane origins. However, it has also become clear that in certain settings methane clumped isotope measurements record kinetic rather than equilibrium isotope effects. Here we present a substantially expanded dataset of methane clumped isotope analyses, and provide a synthesis of the current interpretive framework for this parameter. In general, clumped isotope measurements indicate plausible formation temperatures for abiotic, thermogenic, and microbial methane in many geological environments, which is encouraging for the further development of this measurement as a geothermometer, and as a tracer for the source of natural gas reservoirs and emissions. We also highlight, however, instances where clumped isotope derived temperatures are higher than expected, and discuss possible factors that could distort equilibrium formation temperature signals. In microbial methane from freshwater ecosystems, in particular, clumped isotope values appear to be controlled by kinetic effects, and may ultimately be useful to study methanogen metabolism

Range extension by use of a package-effective CNG-Tank in honeycomb design

The demand for fossil fuels has increased dramatically in recent years. Coupled with the swift rise in crude oil prices, ever greater emissions of greenhouse gases such as CO2 mean that the search for alternatives to fossile fuels based petrol and diesel is essential. The intensified use of natural gas represents an interesting medium-term alternative because, as well as offering a drastic reduction in fuel costs by more than 50%, it also allows a vehicle's CO2 emissions to be reduced by up to 20%, as compared to petrol. Within the scope of the project “Lightweight load-bearing components demonstrated in the form of a gas tank”, which is supported by the federal state of Baden-Württemberg, the german aerospace center’s institute of vehicle concepts, along with 9 partners from research and industry, is developing a CNG-honeycomb-tank intended for storage of CNG or biogas. The tank is made of short-fibre – reinforced thermoplastic with local reinforcements of continuous fibres. Since it is made of multiple interconnected chambers, its shape can be changed to best fit into an existing installation space within the vehicle, leading to an increase in storage capacity of up to 50%. This increase in storage efficiency is combined with a lower price and weight than conventional CNG-storage systems. As proof of the tank’s capabilities a burst test will be conducted in accordance with regulation R 110, using a demonstrator-tank with 9 chambers. This test will presumably be conducted in fall of 2010. The development of the new honeycomb-tank provides a technological advantage in the field of sustainable mobility, particularly because of the increase in storage capacity. The technologies developed during the course of this project can not only pave the way for future storage concepts for gaseous fuel but also make a contribution to extending the application of fibre-reinforced thermoplastic materials to load-bearing components in general

Early Survival Prediction Framework in CD19-Specific CAR-T Cell Immunotherapy Using a Quantitative Systems Pharmacology Model

Chimeric antigen receptor (CAR)-T cell therapy has revolutionized treatment of relapsed/refractory non-Hodgkin lymphoma (NHL). However, since 36–60% of patients relapse, early response prediction is crucial. We present a novel population quantitative systems pharmacology model, integrating literature knowledge on physiology, immunology, and adoptive cell therapy together with 133 CAR-T cell phenotype, 1943 cytokine, and 48 metabolic tumor measurements. The model well described post-infusion concentrations of four CAR-T cell phenotypes and CD19+ metabolic tumor volume over 3 months after CAR-T cell infusion. Leveraging the model, we identified a low expansion subpopulation with significantly lower CAR-T cell expansion capacities amongst 19 NHL patients. Together with two patient-/therapy-related factors (autologous stem cell transplantation, CD4+/CD8+ T cells), the low expansion subpopulation explained 2/3 of the interindividual variability in the CAR-T cell expansion capacities. Moreover, the low expansion subpopulation had poor prognosis as only 1/4 of the low expansion subpopulation compared to 2/3 of the reference population were still alive after 24 months. We translated the expansion capacities into a clinical composite score (CCS) of ‘Maximum naïve CAR-T cell concentrations/Baseline tumor burden’ ratio and propose a CCSTN-value > 0.00136 (cells·µL−1·mL−1 as predictor for survival. Once validated in a larger cohort, the model will foster refining survival prediction and solutions to enhance NHL CAR-T cell therapy response

Anti-ulcer treatment during pregnancy induces food allergy in mouse mothers and a Th2-bias in their offspring

The treatment of dyspeptic disorders with anti-acids leads to an increased risk of sensitization against food allergens. As these drugs are taken by 30-50% of pregnant women due to reflux and heartburn, we aimed here to investigate the impact of maternal therapy with anti-acids on the immune response in the offspring in a murine model. Codfish extract as model allergen was fed with or without sucralfate, an anti-acid drug, to pregnant BALB/c mice during pregnancy and lactation. These mothers developed a codfish-specific allergic response shown as high IgG1 and IgE antibody levels and positive skin tests. In the next step we analyzed whether this maternal sensitization impacts a subsequent sensitization in the offspring. Indeed, in stimulated splenocytes of these offspring we found a relative Th2-dominance, because the Th1- and T-regulatory cytokines were significantly suppressed. Our data provide evidence that the anti-acid drug sucralfate supports sensitization against food in pregnant mice and favors a Th2-milieu in their offspring. From these results we propose that anti-acid treatment during pregnancy could be responsible for the increasing number of sensitizations against food allergens in young infants

Platinum Nanoparticles on Gallium Nitride Surfaces: Effect of Semiconductor Doping on Nanoparticle Reactivity

Platinum nanoparticles supported on n- and p-type gallium nitride (GaN) are investigated as novel hybrid systems for the electronic control of catalytic activity via electronic interactions with the semiconductor support. <i>In situ</i> oxidation and reduction were studied with high pressure photoemission spectroscopy. The experiments revealed that the underlying wide-band-gap semiconductor has a large influence on the chemical composition and oxygen affinity of supported nanoparticles under X-ray irradiation. For as-deposited Pt cuboctahedra supported on n-type GaN, a higher fraction of oxidized surface atoms was observed compared to cuboctahedral particles supported on p-type GaN. Under an oxygen atmosphere, immediate oxidation was recorded for nanoparticles on n-type GaN, whereas little oxidation was observed for nanoparticles on p-type GaN. Together, these results indicate that changes in the Pt chemical state under X-ray irradiation depend on the type of GaN doping. The strong interaction between the nanoparticles and the support is consistent with charge transfer of X-ray photogenerated free carriers at the semiconductor–nanoparticle interface and suggests that GaN is a promising wide-band-gap support material for photocatalysis and electronic control of catalysis