A 135° Gas-Filled Magnet at the Cologne 10 MV AMS FN-Tandem Accelerator Setup and the use of 41Ca as a Reference Nuclide for Nuclear Waste Management

This thesis is focused on the improvement of the measurement capabilities at the Cologne 10MV FN-Tandem accelerator as well as the Cologne 6MV Tandetron accelerator, with respect to accelerator mass spectrometry (AMS). It is separated into four different main topics. The developments and improvements concerning the experimental setups, the data acquisition and data processing on the one hand and on the other hand the measurements of 58Fe/58Ni at the 10MV Tandem accelerator as well as the investigations concerning 41Ca as a new reference nuclide for the topic of nuclear waste management, performed at the 6MV Tandetron accelerator. Both accelerator systems are equipped with a comparable MPA3 data acquisition system. According to the large number of files generated during the AMS measurements, especially during the batch mode measurements at the 6MV Tandetron accelerator, different Python tools were developed to extract and sort the data from these files. Special attention was payed to the generated list mode files, which enables an offline data analysis with respect to signal combinations, the used ROIs and further software conditions. For upcoming measurements of 60Fe, the dedicated AMS beamline at the 10MV Tandem accelerator in combination with a new 135° gas-filled magnet is well suited, since the isobar 60Ni should be suppressed by several orders of magnitude by the use of the new magnet. Within the scope of this thesis, the required tests with stable 58Fe, the tuning procedure and the measurements with the gas-filled magnet were conducted. Investigations at the low energy mass spectrometer revealed that FeO−, in comparison to elemental Fe− or FeO−2 , provide the largest beam output. The new 135° gas-filled magnet was set into operation at the 10MV Tandem accelerator, including a gas handling system for the N2 gas used at the magnet as well as the isobutane gas for the ionization chamber downstream the magnet. The magnetic field homogeneity was determined by a NMR probe to Bhom <1.64e−4 in a range of ±50mm around the optical axis, which is better than the manufacturers specifications of Bhom = 4e−4. Measurements were performed with 58Fe and 58Ni according to the charge state population after the entrance foil of the magnet, resulting in a transmission of 53% through the magnet without N2 gas. The beam width of a 100 MeV 58Fe ion beam passing the gas-filled magnet, with a pressure of 7 mbar N2 gas is d = 12.0mm in the dispersive plane. The separation from the 58Ni component, under these conditions, was measured to 81mm. The existing 10 anode ionization chamber was overhauled and set back into operation. The detector has a total active length of 509mm. First tests with 12C revealed a total energy resolution of Eres = 1.72%. The energy loss in matter was investigated by additional measurements with 40Ca, 39K and 48Ti as well as 58Fe and 58Ni beams. The achieved separation factor for 58Fe and 58Ni at 88 MeV is Sf = 3.9. In parallel, a new 5 anode ionization chamber was developed with an active length of 150mm. The new ionization chamber was tested during a 10Be AMS measurement at the 6MV Tandetron accelerator. The resulting isotopic ratios and the achieved mean correction factor of cf = 2.43 matches the values determined by the reference 4 anode ionization chamber from High Voltage Engineering Europa B.V., used as standard for 10Be measurements at the Cologne 6MV Tandetron accelerator, within the 2-sigma error limits. Measurements with these detectors revealed, that at comparable beam energies of 54 MeV for a 58Fe beam, the separation between 58Fe and 58Ni inside an ionization chamber is 36% larger after the gas-filled magnet than without. The best separation factor of Sf = 4.76 for 58Fe was measured with the 5 anode ionization chamber after the gas-filled magnet, with 7 mbar N2 gas pressure and 28 mbar isobutane gas pressure. Furthermore, stable and reproducible system settings were determined to measure the radionuclide 41Ca at the 6MV Tandetron accelerator. The lowest available standard with a nominal ratio of Rlit(41Ca/Ca) = 5.885e−13 could be measured to R(41Ca/Ca) = 4.70(79)e−13 which corresponds to a correction factor of cf = 1.25. The blank level is 6e−14. Furthermore, 41Ca in concrete material was investigated by irradiating heavy concrete samples with neutrons at the research reactor TRIGA Mark II at Mainz. By choosing different irradiation times, samples with isotopic ratios between e−9 and e−11 could be produced and measured. The expected radioactive activities and isotopic ratios were calculated by taking the full neutron energy spectrum emitted from the research reactor and the corresponding energy depending neutron capture cross sections into account, which results in a mean neutron capture cross section of sigma = 0.28 barn. The comparison of calculated and measured isotopic ratios showed the high precision of the performed AMS measurements and confirms the possibility of investigating concrete samples with AMS methods and obtain informations concerning their radioactive activity and the applied neutron flux. Samples from a biological shield of a research reactor were measured and provided isotopic ratios between 3.92e−9 and 1.21e−8

The Contribution of Housing Renovation to Children\u27s Blood Lead Levels: A Cohort Study

Background Routine renovation of older housing is a risk factor for childhood lead poisoning, but the contribution to children’s blood lead levels is poorly defined for children with lower exposure levels. Methods We examined a prospective cohort of 276 children followed from 6 to 24 months of age. We conducted surveys of renovation activities and residential lead hazards and obtained blood lead level (B-Pb) every six months. We analyzed B-Pb in a repeated measures design using a mixed effects linear model. Results Parent reported interior renovation ranged from 11 to 25% of housing units at the four, 6-month periods. In multivariable analysis, children whose housing underwent interior renovation had a 12% higher mean B-Pb by two years of age compared with children whose housing units were not renovated (p&thinsp;&lt;&thinsp;0.01). The time between renovation and the child blood lead sample was associated with higher B-Pb (p-value for trend &lt;0.01); compared to children in non-renovated housing, children whose housing units underwent renovation in the prior month had a 17% higher mean B-Pb at two years of age, whereas children whose housing renovation occurred in the prior 2–6 months had an 8% higher mean B-Pb. We also found an association between higher paint lead loading, measured using an X-ray fluorescence (XRF) based paint lead index, and child B-Pb (p&thinsp;=&thinsp;0.02); for every 10 mg/cm2 increase in paint lead loading index there was a 7.5% higher mean childhood B-Pb. Conclusions In an analysis of data collected before the recent changes to Environmental Protection Agency’s Lead, Renovation, Repair and Painting Rule, routine interior housing renovation was associated with a modest increase in children’s B-Pb. These results are important for the provision of clinical advice, for housing and public health professionals, and for policymakers

Prenatal Exposure to Bisphenol A and Child Wheeze from Birth to 3 Years of Age

Background: Bisphenol A (BPA), an endocrine-disrupting chemical that is routinely detected in > 90% of Americans, promotes experimental asthma in mice. The association of prenatal BPA exposure and wheeze has not been evaluated in humans

Visible Thermal Emission from Sub-Band-Gap Laser Excited Cerium Dioxide Particles

Cerium dioxide particles excited in air with sub-band-gap radiation emit very broad radiation in the visible spectrum above a threshold intensity that decreases with increasing ambient temperature. Concomitant with this emission is the near disappearance of the Stokes and anti-Stokes Raman scattering peaks. Both phenomena are reversible in air up to just above threshold, and are seen for nanoparticles and several-micron-diameter particles with particle diameter comparable to or smaller than the laser focus. Temperature estimates using the Stokes/anti-Stokes scattering intensity ratio suggest there is laser heating due to small intragap absorption and possible nonlinear processes, given the very slow thermal conduction. The broad emission in this loose powder may well be due to thermal emission, on the basis of spectral fitting of the high-energy part of the spectrum to a blackbody radiator at ϳ1200-1400°C, although luminescence from a new phase is a possibility. The sudden decrease in Raman scattering and increase in emission in air are consistent with a transition to a new, possibly luminescent, phase, as is the continued disappearance of the Raman peaks in forming gas when the laser power is reduced below the upstroke threshold. Oxygen point defects and their complexes may play an important role in many of these processes

A novel multiplex detection array revealed systemic complement activation in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is one of the most common tumors within the oral cavity. Early diagnosis and prognosis tools are urgently needed. This study aimed to investigate the activation of the complement system in OSCC patients as potential biomarker. Therefore, an innovative complement activation array was developed. Characterized antibodies detecting the complement activation specific epitopes C3a, C5a and sC5b-9 along with control antibodies were implemented into a suspension bead array. Human serum from a healthy (n = 46) and OSCC patient (n = 57) cohort were used to investigate the role of complement activation in oral tumor progression. The novel multiplex assay detected C3a, C5a and sC5b-9 from a minimal sample volume of human tears, aqueous humor and blood samples. Limits of detection were 0.04 ng/mL for C3a, 0.03 ng/mL for C5a and 18.9 ng/mL for sC5b-9, respectively. Biological cut-off levels guaranteed specific detections from serum. The mean serum concentration of a healthy control cohort was 680 ng/mL C3a, 70 ng/mL C5a and 2247 ng/mL sC5b-9, respectively. The assay showed an intra-assay precision of 2.9-6.4% and an inter-assay precision of 9.2-18.2%. Increased systemic C5a (p < 0.0001) and sC5b-9 (p = 0.01) concentrations in OSCC patients were determined using the validated multiplex complement assay. Higher C5a concentrations correlated with tumor differentiation and OSCC extension state. Systemic sC5b-9 determination provided a novel biomarker for infiltrating tumor growth and C3a levels were associated with local tumor spreading. Our study suggests that systemic complement activation levels in OSCC patients may be useful to assess disease progression

Loss of MMP-27 Predicts Mandibular Bone Invasion in Oral Squamous Cell Carcinoma

Invasion of the mandibular bone is frequent in oral squamous cell carcinoma (OSCC), which often results in extensive ablative and reconstructive procedures for the patient. The purpose of this single-center, retrospective study was to identify and evaluate potential biomarkers and risk factors for bone invasion in OSCC. Initially, in silico gene expression analysis was performed for different HNSCC tumor T-stages to find factors associated with invasive (T4a) tumor growth. Afterwards, the protein expression of bone-metabolizing MMP-27, TNFRSF11B (Osteoprotegerin, OPG), and TNFSF11 (RANKL) was investigated via Tissue Microarrays (TMAs) for their impact on mandibular bone invasion. TMAs were assembled from the bone–tumor interface of primary OSCCs of the floor of the mouth and gingiva from 119 patients. Sixty-four carcinomas with patho-histological jaw invasion (pT4a) were compared to 55 carcinomas growing along the mandible without invasion (pT2, pT3). Tissue samples were additionally evaluated for patterns of invasion using the WPOI grading system. Statistical analysis of in silico data revealed decreased MMP-27 mRNA expression to be strongly associated with the pT4a-stage in OSCC, indicating invasive tumor growth with infiltration of adjacent anatomical structures. Our own clinico-pathological data on OSCCs presented a significant decrease of MMP-27 in tumors invading the nearby mandible (pT4a), compared to pT2 and pT3 tumors without bone invasion. Loss of MMP27 evolved as the strongest predictor of mandibular bone invasion in binary logistic regression analysis. To our knowledge, this is the first study investigating the role of MMP-27 expression in OSCC and demonstrating the importance of the loss of MMP-27 in mandibular bone invasion

Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial)

Contains fulltext : 69534.pdf (publisher's version ) (Open Access)BACKGROUND: With the availability of infliximab, nowadays recurrent Crohn's disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction.The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohn's disease of the distal ileum with respect to quality of life and costs. METHODS/DESIGN: The study is designed as a multicenter randomized clinical trial including patients with Crohn's disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007. DISCUSSION: The LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohn's disease. TRIAL REGISTRATION: Nederlands Trial Register NTR1150

TGFβ + small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro‐angiogenic phenotype

Transforming growth factor β (TGFβ) is a major component of tumor-derived small extracellular vesicles (TEX) in cancer patients. Mechanisms utilized by TGFβ+ TEX to promote tumor growth and pro-tumor activities in the tumor microenvironment (TME) are largely unknown. TEX produced by head and neck squamous cell carcinoma (HNSCC) cell lines carried TGFβ and angiogenesis-promoting proteins. TGFβ+ TEX stimulated macrophage chemotaxis without a notable M1/M2 phenotype shift and reprogrammed primary human macrophages to a pro-angiogenic phenotype characterized by the upregulation of pro-angiogenic factors and functions. In a murine basement membrane extract plug model, TGFβ+ TEX promoted macrophage infiltration and vascularization (p < 0.001), which was blocked by using the TGFβ ligand trap mRER (p < 0.001). TGFβ+ TEX injected into mice undergoing the 4-nitroquinoline-1-oxide (4-NQO)-driven oral carcinogenesis promoted tumor angiogenesis (p < 0.05), infiltration of M2-like macrophages in the TME (p < 0.05) and ultimately tumor progression (p < 0.05). Inhibition of TGFβ signaling in TEX with mRER ameliorated these pro-tumor activities. Silencing of TGFβ emerges as a critical step in suppressing pro-angiogenic functions of TEX in HNSCC

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio