35 research outputs found

    Diurnal variation of the potassium layer in the upper atmosphere

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    Measurements of the diurnal cycle of potassium (K) atoms between 80 and 110km have been made during October (for the years 2004–2011) using a Doppler lidar at Kühlungsborn, Germany (54.1°N,11.7°E). A pronounced diurnal variation is observed in the K number density, which is explored by using a detailed description of the neutral and ionized chemistry of K in a three-dimensional chemistry climate model. The model captures both the amplitude and phase of the diurnal and semidiurnal variability of the layer, although the peak diurnal amplitude around 90 kmis overestimated. Themodel shows that the total potassium density (≈K+K++KHCO3) exhibits little diurnal variation at each altitude, and the diurnal variations are largely driven by photochemical conversion between these reservoir species. In contrast, tidally driven vertical transport has a small effect at this midlatitude location, and diurnal fluctuations in temperature are of little significance because they are small and the chemistry of K is relatively temperature independent

    EpCAM expression varies significantly and is differentially associated with prognosis in the luminal B HER2+, basal-like, and HER2 intrinsic subtypes of breast cancer

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    BACKGROUND: Epithelial cell adhesion molecule (EpCAM) is frequently expressed in breast cancer, and its expression has been associated with poor prognosis. Breast cancer can be subdivided into intrinsic subtypes, differing in prognosis and response to therapy. METHODS: To investigate the association between EpCAM expression and prognosis in the intrinsic subtypes of breast cancer, we performed immunohistochemical studies on a tissue microarray encompassing a total of 1365 breast cancers with detailed clinicopathological annotation and outcomes data. RESULTS: We observed EpCAM expression in 660 out of 1365 (48%) cases. EpCAM expression varied significantly in the different intrinsic subtypes. In univariate analyses of all cases, EpCAM expression was associated with a significantly worse overall survival. In the intrinsic subtypes, EpCAM expression was associated with an unfavourable prognosis in the basal-like and luminal B HER2(+) subtypes but associated with a favourable prognosis in the HER2 subtype. Consistently, specific ablation of EpCAM resulted in increased cell viability in the breast cancer cell line SKBR3 (ER(−), PR(−), and HER2(+)) but decreased viability in the breast cancer cell line MDA-MB-231 (ER(−), PR(−), and HER2(−) ). CONCLUSION: The differential association of EpCAM expression with prognosis in intrinsic subtypes has important implications for the development of EpCAM-targeted therapies in breast cancer

    Generation of mammaglobin-A-specific CD4 T cells and identification of candidate CD4 epitopes for breast cancer vaccine strategies

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    BACKGROUND: Mammaglobin-A (MGB) is a breast cancer-associated antigen that is an attractive target for immune intervention. MGB has been shown to induce a specific CD8 T cell response in breast cancer patients, but little is known about a possible MGB-specific CD4 T cell response. METHODS: Peripheral blood-derived CD4(+)CD25(-) T cells were stimulated in vitro with MGB-pulsed antigen-presenting cells (APC). The MGB and human leukocyte antigen (HLA) class II specificity of the CD4 T cell lines was confirmed by cytokine release following restimulation with autologous and allogenic APC pulsed with MGB from different sources. Candidate HLA class II-restricted epitopes were identified by computer algorithm and validated in cytokine release assays. RESULTS: MGB-specific CD4 T cells were successfully generated in cultures from six of seven donors. Restimulation of MGB-specific CD4 T cells with MGB-pulsed APC induced significantly higher levels of interferon (IFN)-gamma release than APC pulsed with an irrelevant protein (P = 0.0004). Cultures from five of seven donors showed a pure Th1 type response as evidenced by the absence of interleukin (IL)-4. MGB-specific CD4 T cells recognized both recombinant and naturally processed MGB presented by APC. This recognition was HLA class II-restricted, as HLA-DR mismatched APC were not recognized. MGB-specific CD4 T cells from three of four donors recognized MGB-derived, HLA class II-restricted peptides pulsed onto APC. CONCLUSIONS: We have successfully generated MGB-specific CD4 T cell cultures and identified candidate MGB HLA class II epitopes. These studies should facilitate study of the CD4 T cell response to MGB, and the development and monitoring of vaccine strategies targeting this unique antigen

    Winter/summer mesopause temperature transition at Davis (69°S) in 2011/2012

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    We present quasi-continuous measurements of temperature profiles in the Southern Hemisphere mesopause region during the transition from winter to summer conditions in 2011/2012. In a period of 120 days around solstice, we have performed iron lidar observations at Davis (69°S), Antarctica, for a total of 736 h. The winter/summer transition is identified by a downward shift of the mesopause which occurs on 8 November 2011. Soon after transition, mesopause heights and temperatures are similar to the Northern Hemisphere (NH) colatitude summer (88 km, 130 K). Around solstice, the mesopause is elevated for several days by 4–5 km and is colder than typical NH temperatures by 10 K. In this period individual profiles show temperatures as low as 100 K. The occurrence of polar mesosphere summer echoes is closely connected to low temperatures. Below 88 to 90 km and in the main summer season of 2011/2012 temperatures at Davis are generally warmer compared to the NH by 5–15 K, whereas temperatures are generally colder above 90 km. The winter/summer transition and the first appearance of polar mesosphere summer echoes are strongly correlated to maximum zonal winds in the stratosphere which constrain gravity waves with eastward momentum reaching the mesosphere. At the breakdown of the stratospheric vortex around solstice, the mesopause is higher and, surprisingly, colder than normal

    The thermal and dynamical state of the Antarctic mesopause region during winter/summer transition and the role of stratosphere/mesosphere coupling

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    The transition of stratospheric circulation at Antarctic latitudes from winter to summer conditions is highly variably from year to year. As has been realized recently, this also affects the winter/summer transition at mesopause altitudes. The Antarctic middle atmosphere therefore offers the unique possibility to study the physical processes involved in the vertical coupling between the stratosphere and the mesosphere during winter/summer transition, in particular the role of gravity waves. We present new results from the mobile scanning iron lidar of the Leibniz Institute of Atmospheric Physics in Kühlungsborn (IAP) which was in operation at Davis, Antarctica, from December 15, 2010, until December 31, 2012. It measured temperatures in the iron layer (~80-100 km). The lidar can operate under daylight conditions. At Davis, the lidar has achieved at total of 2900 hours of temperature measurements which is presumably the largest nearly continuous data set in Antarctica. In this presentation we concentrate on the winter/summer transition and compare with circulation changes in the stratosphere derived from MERRA. We also compare with the northern hemisphere (NH). The thermal structure around the mesopause at Davis is closely coupled to the general circulation in the stratosphere, more precisely to the transition from winter to summer conditions. In contrast to theoretical expectations we occasionally find the mesopause significantly higher and colder(!) compared to the NH. The mesopause altitude changes by several kilometers throughout the summer season, which is significantly different from the summer in the northern hemispheric. Depending on altitude, temperatures can be warmer or colder compared to the NH summer. We studied the seasonal variation of polar mesosphere summer echoes (PMSE). PMSE are strong radar echoes related to ice particles and therefore require very low atmospheric temperatures. The VHF radar frequently detected PMSE. We compare the seasonal variation of PMSE with stratospheric circulation, both at Davis and at ALOMAR (69°N). We also compare with winds in the upper mesosphere measured by a MF radar also located at Davis. Model calculations applying the Kühlungsborn Mechanistic Circulation Model (KMCM) are used to better understand the stratosphere/mesosphere coupling

    Accuracy of frozen section analysis versus specimen radiography during breast-conserving surgery for nonpalpable lesions

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    BACKGROUND: Whereas specimen radiography (SR) is an established strategy for intraoperative resection margin analysis during breast-conserving surgery for nonpalpable lesions, the use of frozen section analysis (FSA) is still a matter of debate. METHODS: A retrospective review was conducted of 115 consecutive operations in which the two objectives sought were the excision of nonpalpable malignant lesions and breast conservation. Breast surgery was performed in the Gynecology and the Surgery Departments at the Basel University Hospital Breast Center. Whereas one department preferably uses SR for intraoperative margin assessments of lesions involving ductal carcinoma in situ (DCIS) or atypical ductal hyperplasia, the other uses FSA to increase the rate of complete removal of these lesions with a single procedure. The respective accuracy and therapeutic impact of these two techniques are compared here. RESULTS: Intraoperative resection margin assessments were performed with FSA in 80 and SR in 35 of a total of 115 operations performed on 111 patients with pTis, pT1, or pT2 nonpalpable breast cancer. FSA diagnostic accuracy, sensitivity, and specificity were 83.8%, 80.0%, and 87.5%, respectively, compared to 60%, 60%, and 60%, respectively, for SR. FSA tended to have a stronger therapeutic impact than SR in terms of the number of patients in whom initially positive margins were rendered margin-negative thanks to intraoperative analysis and immediate reexcision or mastectomy (27.5% vs. 14.3%; p = 0.124). More importantly, significantly fewer secondary reexcisions were performed in the FSA series than in the SR series (12.5% vs. 37.1%; p = 0.002). Finally, the intraoperative detection of invasive cancer with FSA led to a significantly lower number of secondary procedures for axillary lymph node staging (5% vs. 25.7%; p = 0.001). CONCLUSIONS: The present results suggest that FSA may be more accurate than SR for analyzing intraoperative resection margins during breast-conserving surgery for nonpalpable lesions

    Radiation hard strip detectors for large-scale silicon trackers

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    Major challenges in building silicon strip detectors for future high luminosity experiments are the high radiation level and the huge number of sensors required for the construction of the precision layers of the complete tracking system. Single-sided p/sup +/n strip detectors for ATLAS SCT designed and fabricated at the MPI Semiconductor Laboratory have been exposed to 3*10/sup 14//cm/sup 2/ 24 GeV protons. The major features of the design, including the biasing technique using implanted resistors, are discussed and results are presented. The technology was transferred to CiS, Germany, a company capable of the desired large-scale production. Results of this industrially fabricated sensors look very promising and show the expected radiation hardness. (12 refs)
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