Analysis of the 207Bi, 194Hg/Au and 173Lu distribution in the irradiated MEGAPIE target

Samples obtained from different locations within the prototype liquid metal spallation target MEGAPIE irradiated in 2006 at PSI were analysed using γ-spectrometry. A variety of radionuclides formed by reaction of the target material, lead–bismuth eutectic (LBE), with the proton beam and secondary particles were identified. While nuclides representing the target material itself (207Bi) and nuclides of noble metals were found in LBE samples throughout the target, nuclides of electropositive metals were found to be quantitatively deposited on free surfaces and material interfaces within the target system. This behaviour is analysed in more detail based on results obtained for three nuclides representing groups of elements with distinct chemical behaviour, namely 207Bi, 194Hg/Au and 173Lu. Quantitative analysis results are given and compared with predictions obtained using nuclear physics calculations for those nuclides showing rather homogeneous distribution within the target. Possible reasons for the separation of radionuclides from the liquid metal and their deposition on surfaces are given, and consequences arising for nuclear facilities utilizing liquid metals are discussed.

Responses of lung cells to realistic exposure of primary and aged carbonaceous aerosols

Diesel exhaust and wood burning are important sources of ambient atmospheric particles due to increasing numbers of diesel cars and the importance of wood as a source of renewable energy. Inhalation is the predominant route of entry and uptake for fine and ultrafine particles into the body. Health effects of atmospheric particles are still not completely understood. There is consistent evidence from epidemiology that particle exposure contributes to respiratory and cardiovascular diseases. This study aimed at examining acute responses of airway epithelial cells and luminal macrophages after exposure to freshly emitted and photochemically aged carbonaceous aerosols under realistic atmospheric conditions. In addition to a bronchial epithelial cell line advanced cell cultures namely fully differentiated respiratory epithelia and primary surface macrophages were used. Our results demonstrate that a single exposure of the cells to realistic particle doses of 0.3–3 ng diesel or 3–9 ng wood aerosol per cm2 cell surface induces small, particle-specific responses. The release of interleukin-6 and -8 was found to be decreased in differentiated airway epithelia but not in the other cell models studied. Aerosol exposure decreased macrophage phagocytic activity by 45–90%. Cell and tissue integrity remained unaffected. Overall, primary and aged particles from the same combustion induced similar responses in the cell models tested, whereby particles from diesel exhaust affected the cells more than those from wood combustion.

Prognostic significance of xCT polymorphisms and expression in patients with advanced pancreatic cancer treated with chemotherapy

The plasma membrane xc- cystine/glutamate transporter mediates cellular uptake of cystine in exchange for intracellular glutamate and is highly expressed by pancreatic cancer cells. The xCT gene, encoding the cystine-specific xCT protein subunit of xc-, is important in regulating intracellular glutathione (GSH) levels, critical for cancer cell protection against oxidative stress, tumor growth and resistance to chemotherapeutic agents including platinum. We examined 4 single nucleotide polymorphisms (SNPs) of the xCT gene in 269 advanced pancreatic cancer patients who received first line gemcitabine with or without cisplatin or oxaliplatin. Genotyping was performed using Taqman real-time PCR assays. A statistically significant correlation was noted between the 3' untranslated region (UTR) xCT SNP rs7674870 and overall survival (OS): Median survival time (MST) was 10.9 and 13.6 months, respectively, for the TT and TC/CC genotypes (p = 0.027). Stratified analysis showed the genotype effect was significant in patients receiving gemcitabine in combination with platinum therapy (n = 145): MST was 10.5 versus 14.1 months for the TT and TC/CC genotypes, respectively (p = 0.013). The 3' UTR xCT SNP rs7674870 may correlate with OS in pancreatic cancer patients receiving gemcitabine and platinum combination therapy. Paraffin-embedded core and surgical biopsy tumor specimens from 98 patients with metastatic pancreatic adenocarcinoma were analyzed by immunohistochemistry using an xCT specific antibody. xCT protein IHC expression scores were analyzed in relation to overall survival in 86 patients and genotype in 12 patients and no statistically significant association was found between the level of xCT IHC expression score and overall survival (p = 0.514). When xCT expression was analyzed in terms of treatment response, no statistically significant associations could be determined (p = 0.908). These data suggest that polymorphic variants of xCT may have predictive value, and that the xc- transporter may represent an important target for therapy in pancreatic cancer.

THE CALIBRATION AND IMPLEMENTATION OF CR-39 NUCLEAR TRACK DETECTOR MATERIAL AS A FAST NEUTRON MICRODOSIMETER

A detailed microdosimetric characterization of the M. D. Anderson 42 MeV (p,Be) fast neutron beam was performed using the techniques of microdosimetry and a 1/2 inch diameter Rossi proportional counter. These measurements were performed at 5, 15, and 30 cm depths on the central axis, 3 cm inside, and 3 cm outside the field edge for 10 $\times$ 10 and 20 $\times$ 20 cm field sizes. Spectra were also measured at 5 and 15 cm depth on central axis for a 6 $\times$ 6 cm field size. Continuous slowing down approximation calculations were performed to model the nuclear processes that occur in the fast neutron beam. Irradiation of the CR-39 was performed using a tandem electrostatic accelerator for protons of 10, 6, and 3 MeV and alpha particles of 15, 10, and 7 MeV incident energy on target at angles of incidence from 0 to 85 degrees. The critical angle as well as track etch rate and normal incidence diameter versus linear energy transfer (LET) were obtained from these measurements. The bulk etch rate was also calculated from these measurements. Dose response of the material was studied, and the angular distribution of charged particles created by the fast neutron beam was measured with CR-39. The efficiency of CR-39 was calculated versus that of the Rossi chamber, and an algorithm was devised for derivation of LET spectra from the major and minor axis dimensions of the observed tracks. The CR-39 was irradiated in the same positions as the Rossi chamber, and the derived spectra were compared directly. ^

Impact of solar versus volcanic activity variations on tropospheric temperatures and precipitation during the Dalton Minimum

The aim of this work is to elucidate the impact of changes in solar irradiance and energetic particles versus volcanic eruptions on tropospheric global climate during the Dalton Minimum (DM, AD 1780–1840). Separate variations in the (i) solar irradiance in the UV-C with wavelengths λ < 250 nm, (ii) irradiance at wavelengths λ > 250 nm, (iii) in energetic particle spectrum, and (iv) volcanic aerosol forcing were analyzed separately, and (v) in combination, by means of small ensemble calculations using a coupled atmosphere–ocean chemistry–climate model. Global and hemispheric mean surface temperatures show a significant dependence on solar irradiance at λ > 250 nm. Also, powerful volcanic eruptions in 1809, 1815, 1831 and 1835 significantly decreased global mean temperature by up to 0.5 K for 2–3 years after the eruption. However, while the volcanic effect is clearly discernible in the Southern Hemispheric mean temperature, it is less significant in the Northern Hemisphere, partly because the two largest volcanic eruptions occurred in the SH tropics and during seasons when the aerosols were mainly transported southward, partly because of the higher northern internal variability. In the simulation including all forcings, temperatures are in reasonable agreement with the tree ring-based temperature anomalies of the Northern Hemisphere. Interestingly, the model suggests that solar irradiance changes at λ < 250 nm and in energetic particle spectra have only an insignificant impact on the climate during the Dalton Minimum. This downscales the importance of top–down processes (stemming from changes at λ < 250 nm) relative to bottom–up processes (from λ > 250 nm). Reduction of irradiance at λ > 250 nm leads to a significant (up to 2%) decrease in the ocean heat content (OHC) between 0 and 300 m in depth, whereas the changes in irradiance at λ < 250 nm or in energetic particles have virtually no effect. Also, volcanic aerosol yields a very strong response, reducing the OHC of the upper ocean by up to 1.5%. In the simulation with all forcings, the OHC of the uppermost levels recovers after 8–15 years after volcanic eruption, while the solar signal and the different volcanic eruptions dominate the OHC changes in the deeper ocean and prevent its recovery during the DM. Finally, the simulations suggest that the volcanic eruptions during the DM had a significant impact on the precipitation patterns caused by a widening of the Hadley cell and a shift in the intertropical convergence zone.

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of root s = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K-s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5 % for central isolated hadrons and 1-3 % for the final calorimeter jet energy scale.

Sheep macrophages express at least two distinct receptors for IgG which have similar affinity for homologous IgG1 and IgG2.

Ovine bone marrow-derived macrophages (BMM) may express several IgG receptor (Fc gamma receptor; FcR) subsets. To study this, model particles (opsonized erythrocytes; EA), which are selectively handled by certain FcR subsets of human macrophages were used in cross-inhibition studies and found to react in a similar manner with FcR subsets of sheep macrophages. In experiments with monoclonal antibodies against subsets of human FcR, human erythrocytes (E) treated with human anti-D-IgG (anti-D-EAhu) and sheep E treated with bovine IgG1 (Bo1-EAs) were handled selectively by human macrophage FcRI and FcRII, respectively. Rabbit-IgG-coated sheep E (Rb-EAs) were recognized by FcRI, FcRII and possibly also by FcRIII of human macrophages. Anti-D-EAhu, Bo1-EAs and Rb-EAs were also ingested by sheep BMM. Competitive inhibition tests, using various homologous and heterologous IgG isotypes as fluid phase inhibitors and the particles used as FcR-specific tools in man (anti-D-EAhu and Bo1-EAs), revealed a heterogeneity of FcR also in sheep BMM. Thus, ingestion of anti-D-EAhu by ovine BMM was inhibited by low concentrations of competitor IgG from rabbit or man in the fluid phase, but not at all by bovine IgG1, whereas ingestion of Bo1-EAs was inhibited by bovine IgG1. This suggested that anti-D-EAhu were recognized by a FcR subset distinct from that recognizing bovine-IgG1. It was concluded that sheep BMM express functional analogs of human macrophage FcRI and FcRII and that Bo1-EAs and anti-D-EAhu are handled by distinct subsets of BMM FcR. All EAhu tested (EAhu treated with anti-D, sheep IgG1 or sheep IgG2) were ingested to a lower degree than EAs. This inefficient phagocytosis could be enhanced by treatment of EAhu with antiglobulin from the rabbit, suggesting that it is caused by a low degree of activity of opsonizing antibodies rather than special properties of the erythrocytes themselves. Several lines of evidence suggested that both FcR subsets of ovine BMM recognize both ovine IgG1 and IgG2. In contrast, bovine IgG1 reacts with one FcR subset and bovine IgG2 interacts inefficiently with all FcR of ovine BMM.

Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids.

BACKGROUND Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. PATIENTS AND METHODS Bibliographical searches were carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review of the relevant literature was carried out, followed by expert review. RESULTS PCs are well-differentiated neuroendocrine tumors and include low- and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs, but pathology examination is mandatory for their correct classification. Somatostatin receptor imaging may visualize nearly 80% of the primary tumors and is most sensitive for metastatic disease. Plasma chromogranin A can be increased in PCs. Surgery is the treatment of choice for PCs with the aim of removing the tumor and preserving as much lung tissue as possible. Resection of metastases should be considered whenever possible with curative intent. Somatostatin analogs are the first-line treatment of carcinoid syndrome and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC. Locoregional or radiotargeted therapies should be considered for metastatic disease. Systemic chemotherapy is used for progressive PCs, although cytotoxic regimens have demonstrated limited effects with etoposide and platinum combination the most commonly used, however, temozolomide has shown most clinical benefit. CONCLUSIONS PCs are complex tumors which require a multidisciplinary approach and long-term follow-up.

Chemical compositions of solid particles present in the Greenland NEEM ice core over the last 110,000 years

This study reports the chemical composition of particles present along Greenland’s North Greenland Eemian Ice Drilling (NEEM) ice core, back to 110,000 years before present. Insoluble and soluble particles larger than 0.45 μm were extracted from the ice core by ice sublimation, and their chemical composition was analyzed using scanning electron microscope and energy dispersive X-ray spectroscopy and micro-Raman spectroscopy. We show that the dominant insoluble components are silicates, whereas NaCl, Na₂SO₄, CaSO ₄, and CaCO₃ represent major soluble salts. For the first time, particles of CaMg(CO₃)₂ and Ca(NO₃)₂ 4H₂O are identified in a Greenland ice core. The chemical speciation of salts varies with past climatic conditions. Whereas the fraction of Na salts (NaCl + Na₂SO₄) exceeds that of Ca salts (CaSO₄+ CaCO₃) during the Holocene (0.6–11.7 kyr B.P.), the two fractions are similar during the Bølling-Allerød period (12.9–14.6 kyr B.P.). During cold climate such as over the Younger Dryas (12.0–12.6 kyr B.P.) and the Last Glacial Maximum (15.0–26.9 kyr B.P.), the fraction of Ca salts exceeds that of Na salts, showing that the most abundant ion generally controls the salt budget in each period. High-resolution analyses reveal changing particle compositions: those in Holocene ice show seasonal changes, and those in LGM ice show a difference between cloudy bands and clear layers, which again can be largely explained by the availability of ionic components in the atmospheric aerosol body of air masses reaching Greenland.

The calculation of Afρ and mass loss rate for comets

Ab initio calculations of Afρ are presented using Mie scattering theory and a Direct Simulation Monte Carlo (DSMC) dust outflow model in support of the Rosetta mission and its target 67P/Churyumov-Gerasimenko (CG). These calculations are performed for particle sizes ranging from 0.010 μm to 1.0 cm. The present status of our knowledge of various differential particle size distributions is reviewed and a variety of particle size distributions is used to explore their effect on Afρ , and the dust mass production View the MathML sourcem˙. A new simple two parameter particle size distribution that curtails the effect of particles below 1 μm is developed. The contributions of all particle sizes are summed to get a resulting overall Afρ. The resultant Afρ could not easily be predicted a priori and turned out to be considerably more constraining regarding the mass loss rate than expected. It is found that a proper calculation of Afρ combined with a good Afρ measurement can constrain the dust/gas ratio in the coma of comets as well as other methods presently available. Phase curves of Afρ versus scattering angle are calculated and produce good agreement with observational data. The major conclusions of our calculations are: – The original definition of A in Afρ is problematical and Afρ should be: qsca(n,λ)×p(g)×f×ρqsca(n,λ)×p(g)×f×ρ. Nevertheless, we keep the present nomenclature of Afρ as a measured quantity for an ensemble of coma particles.– The ratio between Afρ and the dust mass loss rate View the MathML sourcem˙ is dominated by the particle size distribution. – For most particle size distributions presently in use, small particles in the range from 0.10 to 1.0 μm contribute a large fraction to Afρ. – Simplifying the calculation of Afρ by considering only large particles and approximating qsca does not represent a realistic model. Mie scattering theory or if necessary, more complex scattering calculations must be used. – For the commonly used particle size distribution, dn/da ∼ a−3.5 to a−4, there is a natural cut off in Afρ contribution for both small and large particles. – The scattering phase function must be taken into account for each particle size; otherwise the contribution of large particles can be over-estimated by a factor of 10. – Using an imaginary index of refraction of i = 0.10 does not produce sufficient backscattering to match observational data. – A mixture of dark particles with i ⩾ 0.10 and brighter silicate particles with i ⩽ 0.04 matches the observed phase curves quite well. – Using current observational constraints, we find the dust/gas mass-production ratio of CG at 1.3 AU is confined to a range of 0.03–0.5 with a reasonably likely value around 0.1.

Genetic variants in the mammalian target of rapamycin (mTOR) signaling pathway as predictors of survival and clinical response in women with ovarian cancer

Background. The mTOR pathway is commonly altered in human tumors and promotes cell survival and proliferation. Preliminary evidence suggests this pathway's involvement in chemoresistance to platinum and taxanes, first line therapy for epithelial ovarian cancer. A pathway-based approach was used to identify individual germline single nucleotide polymorphisms (SNPs) and cumulative effects of multiple genetic variants in mTOR pathway genes and their association with clinical outcome in women with ovarian cancer. ^ Methods. The case-series was restricted to 319 non-Hispanic white women with high grade ovarian cancer treated with surgery and platinum-based chemotherapy. 135 SNPs in 20 representative genes in the mTOR pathway were genotyped. Hazard ratios (HRs) for death and Odds ratios (ORs) for failure to respond to primary therapy were estimated for each SNP using the multivariate Cox proportional hazards model and multivariate logistic regression model, respectively, while adjusting for age, stage, histology and treatment sequence. A survival tree analysis of SNPs with a statistically significant association (p<0.05) was performed to identify higher order gene-gene interactions and their association with overall survival. ^ Results. There was no statistically significant difference in survival by tumor histology or treatment regimen. The median survival for the cohort was 48.3 months. Seven SNPs were significantly associated with decreased survival. Compared to those with no unfavorable genotypes, the HR for death increased significantly with the increasing number of unfavorable genotypes and women in the highest risk category had HR of 4.06 (95% CI 2.29–7.21). The survival tree analysis also identified patients with different survival patterns based on their genetic profiles. 13 SNPs on five different genes were found to be significantly associated with a treatment response, defined as no evidence of disease after completion of primary therapy. Rare homozygous genotype of SNP rs6973428 showed a 5.5-fold increased risk compared to the wild type carrying genotypes. In the cumulative effect analysis, the highest risk group (individuals with ≥8 unfavorable genotypes) was significantly less likely to respond to chemotherapy (OR=8.40, 95% CI 3.10–22.75) compared to the low risk group (≤4 unfavorable genotypes). ^ Conclusions. A pathway-based approach can demonstrate cumulative effects of multiple genetic variants on clinical response to chemotherapy and survival. Therapy targeting the mTOR pathway may modify outcome in select patients.^

Northwards and eastwards velocities extracted from a historical run (for the year 2000) of the UVic Earth System Climate Model of Weaver et al. (2001)

This study provides a theoretical assessment of the potential bias due to differential lateral transport on multi-proxy studies based on a range of marine microfossils. Microfossils preserved in marine sediments are at the centre of numerous proxies for paleoenvironmental reconstructions. The precision of proxies is based on the assumption that they accurately represent the overlying watercolumn properties and faunas. Here we assess the possibility of a syn-depositional bias in sediment assemblages caused by horizontal drift in the water column, due to differential settling velocities of sedimenting particles based on their shape, size and density, and due to differences in current velocities. Specifically we calculate the post-mortem lateral transport undergone by planktic foraminifera and a range of other biological proxy carriers (diatoms, radiolaria and fecal pellets transporting coccolithophores) in several regions with high current velocities. We find that lateral transport of different planktic foraminiferal species is minimal due to high settling velocities. No significant shape- or size-dependent sorting occurs before reaching the sediment, making planktic foraminiferal ideal proxy carriers. In contrast, diatoms, radiolaria and fecal pellets can be transported up to 500km in some areas. For example in the Agulhas current, transport can lead to differences of up to 2°C in temperature reconstructions between different proxies in response to settling velocities. Therefore, sediment samples are likely to contain different proportions of local and imported particles, decreasing the precision of proxies based on these groups and the accuracy of the temperature reconstruction.

Zooplankton abundance and size structure in the North Atlantic from MSM26_133-14

Data on zooplankton abundance and biovolume were collected in concert with data on the biophysical environment at 9 stations in the North Atlantic, from the Iceland Basin in the East to the Labrador Sea in the West. The data were sampled along vertical profiles by a Laser Optical Plankton Counter (LOPC, Rolls Royce Canada Ltd.) that was mounted on a carousel water sampler together with a Conductivity-Temperature-Depth sensor (CTD, SBE19plusV2, Seabird Electronics, Inc., USA) and a fluorescence sensor (F, ECO Puck chlorophyll a fluorometer, WET Labs Inc., USA). Based on the LOPC data, abundance (individuals/m**3) and biovolume (mm3/m**3) were calculated as described in the LOPC Software Operation Manual [(Anonymous, 2006), http://www.brooke-ocean.com/index.html]. LOPC data were regrouped into 49 size groups of equal log10(body volume) increments, see Edvardsen et al. (2002, doi:10.3354/meps227205). LOPC data quality was checked as described in Basedow et al. (2013, doi:10.1016/j.pocean.2012.10.005). Fluorescence was roughly converted into chlorophyll based on filtered chlorophyll values obtained from station 10 in the Labrador Sea. Due to the low number of filtered samples that was used for the conversion the resulting chlorophyll values should be considered with care. CTD data were screened for erroneous (out of range) values and then averaged to the same frequency as the LOPC data (2 Hz). All data were processed using especially developed scripts in the python programming language. The LOPC is an optical instrument designed to count and measure particles (0.1 to 30 mm equivalent spherical diameter) in the water column, see Herman et al., (2004, doi:10.1093/plankt/fbh095). The size of particles as equivalent spherical diameter (ESD) was computed as described in the manual (Anonymous, 2006), and in more detail in Checkley et al. (2008, doi:10.4319/lo.2008.53.5_part_2.2123) and Gaardsted et al. (2010, doi:10.1111/j.1365-2419.2010.00558.x).

Zooplankton abundance and size structure in the North Atlantic from MSM26_135-21

Data on zooplankton abundance and biovolume were collected in concert with data on the biophysical environment at 9 stations in the North Atlantic, from the Iceland Basin in the East to the Labrador Sea in the West. The data were sampled along vertical profiles by a Laser Optical Plankton Counter (LOPC, Rolls Royce Canada Ltd.) that was mounted on a carousel water sampler together with a Conductivity-Temperature-Depth sensor (CTD, SBE19plusV2, Seabird Electronics, Inc., USA) and a fluorescence sensor (F, ECO Puck chlorophyll a fluorometer, WET Labs Inc., USA). Based on the LOPC data, abundance (individuals/m**3) and biovolume (mm3/m**3) were calculated as described in the LOPC Software Operation Manual [(Anonymous, 2006), http://www.brooke-ocean.com/index.html]. LOPC data were regrouped into 49 size groups of equal log10(body volume) increments, see Edvardsen et al. (2002, doi:10.3354/meps227205). LOPC data quality was checked as described in Basedow et al. (2013, doi:10.1016/j.pocean.2012.10.005). Fluorescence was roughly converted into chlorophyll based on filtered chlorophyll values obtained from station 10 in the Labrador Sea. Due to the low number of filtered samples that was used for the conversion the resulting chlorophyll values should be considered with care. CTD data were screened for erroneous (out of range) values and then averaged to the same frequency as the LOPC data (2 Hz). All data were processed using especially developed scripts in the python programming language. The LOPC is an optical instrument designed to count and measure particles (0.1 to 30 mm equivalent spherical diameter) in the water column, see Herman et al., (2004, doi:10.1093/plankt/fbh095). The size of particles as equivalent spherical diameter (ESD) was computed as described in the manual (Anonymous, 2006), and in more detail in Checkley et al. (2008, doi:10.4319/lo.2008.53.5_part_2.2123) and Gaardsted et al. (2010, doi:10.1111/j.1365-2419.2010.00558.x).