Impact of loading displacements on SLR-derived parameters and on the consistency between GNSS and SLR results

Displacements of the Earth’s surface caused by tidal and non-tidal loading forces are relevant in high-precision space geodesy. Some of the corrections are recommended by the international scientific community to be applied at the observation level, e.g., ocean tidal loading (OTL) and atmospheric tidal loading (ATL). Non-tidal displacement corrections are in general recommended not to be applied in the products of the International Earth Rotation and Reference Systems Service, in particular atmospheric non-tidal loading (ANTL), oceanic and hydrological non-tidal corrections. We assess and compare the impact of OTL, ATL and ANTL on SLR-derived parameters by reprocessing 12 years of SLR data considering and ignoring individual corrections. We show that loading displacements have an influence not only on station long-term stability, but also on geocenter coordinates, Earth Rotation Parameters, and satellite orbits. Applying the loading corrections reduces the amplitudes of annual signals in the time series of geocenter and station coordinates. The general improvement of the SLR station 3D coordinate repeatability when applying OTL, ATL and ANTL corrections are 19.5 %, 0.2 % and 3.3 % respectively, w.r.t. the solutions without loading corrections. ANTL corrections play a crucial role in the combination of optical (SLR) and microwave (GNSS, VLBI, DORIS) space geodetic observation techniques, because of the so-called Blue-Sky effect: SLR measurements can be carried out only under cloudless sky conditions—typically during high air pressure conditions, when the Earth’s crust is deformed, whereas microwave observations are weather-independent. Thus, applying the loading corrections at the observation level improves SLR-derived products as well as the consistency with microwave-based results. We assess the Blue-Sky effect on SLR stations and the consistency improvement between GNSS and SLR solutions when ANTL corrections are included. The omission of ANTL corrections may lead to inconsistencies between SLR and GNSS solutions of up to 2.5 mm for inland stations. As a result, the estimated GNSS–SLR coordinate differences correspond better to the local ties at the co-located stations when applying ANTL corrections.

Thoracic radiotherapy treatment planning with cine PET/CT

Purpose: Respiratory motion causes substantial uncertainty in radiotherapy treatment planning. Four-dimensional computed tomography (4D-CT) is a useful tool to image tumor motion during normal respiration. Treatment margins can be reduced by targeting the motion path of the tumor. The expense and complexity of 4D-CT, however, may be cost-prohibitive at some facilities. We developed an image processing technique to produce images from cine CT that contain significant motion information without 4D-CT. The purpose of this work was to compare cine CT and 4D-CT for the purposes of target delineation and dose calculation, and to explore the role of PET in target delineation of lung cancer. Methods: To determine whether cine CT could substitute 4D-CT for small mobile lung tumors, we compared target volumes delineated by a physician on cine CT and 4D-CT for 27 tumors with intrafractional motion greater than 1 cm. We assessed dose calculation by comparing dose distributions calculated on respiratory-averaged cine CT and respiratory-averaged 4D-CT using the gamma index. A threshold-based PET segmentation model of size, motion, and source-to-background was developed from phantom scans and validated with 24 lung tumors. Finally, feasibility of integrating cine CT and PET for contouring was assessed on a small group of larger tumors. Results: Cine CT to 4D-CT target volume ratios were (1.05±0.14) and (0.97±0.13) for high-contrast and low-contrast tumors respectively which was within intraobserver variation. Dose distributions on cine CT produced good agreement (< 2%/1 mm) with 4D-CT for 71 of 73 patients. The segmentation model fit the phantom data with R2 = 0.96 and produced PET target volumes that matched CT better than 6 published methods (-5.15%). Application of the model to more complex tumors produced mixed results and further research is necessary to adequately integrate PET and cine CT for delineation. Conclusions: Cine CT can be used for target delineation of small mobile lesions with minimal differences to 4D-CT. PET, utilizing the segmentation model, can provide additional contrast. Additional research is required to assess the efficacy of complex tumor delineation with cine CT and PET. Respiratory-averaged cine CT can substitute respiratory-averaged 4D-CT for dose calculation with negligible differences.

Thoracic target volume delineation using various maximum-intensity projection computed tomography image sets for stereotactic body radiation therapy

The motion of lung tumors during respiration makes the accurate delivery of radiation therapy to the thorax difficult because it increases the uncertainty of target position. The adoption of four-dimensional computed tomography (4D-CT) has allowed us to determine how a tumor moves with respiration for each individual patient. Using information acquired during a 4D-CT scan, we can define the target, visualize motion, and calculate dose during the planning phase of the radiotherapy process. One image data set that can be created from the 4D-CT acquisition is the maximum-intensity projection (MIP). The MIP can be used as a starting point to define the volume that encompasses the motion envelope of the moving gross target volume (GTV). Because of the close relationship that exists between the MIP and the final target volume, we investigated four MIP data sets created with different methodologies (3 using various 4D-CT sorting implementations, and one using all available cine CT images) to compare target delineation. It has been observed that changing the 4D-CT sorting method will lead to the selection of a different collection of images; however, the clinical implications of changing the constituent images on the resultant MIP data set are not clear. There has not been a comprehensive study that compares target delineation based on different 4D-CT sorting methodologies in a patient population. We selected a collection of patients who had previously undergone thoracic 4D-CT scans at our institution, and who had lung tumors that moved at least 1 cm. We then generated the four MIP data sets and automatically contoured the target volumes. In doing so, we identified cases in which the MIP generated from a 4D-CT sorting process under-represented the motion envelope of the target volume by more than 10% than when measured on the MIP generated from all of the cine CT images. The 4D-CT methods suffered from duplicate image selection and might not choose maximum extent images. Based on our results, we suggest utilization of a MIP generated from the full cine CT data set to ensure a representative inclusive tumor extent, and to avoid geometric miss.

Genetic Control of Plant Development by Overriding a Geometric Division Rule

Formative cell divisions are critical for multicellular patterning. In the early plant embryo, such divisions follow from orienting the division plane. A major unanswered question is how division plane orientation is genetically controlled, and in particular whether this relates to cell geometry. We have generated a complete 4D map of early Arabidopsis embryogenesis and used computational analysis to demonstrate that several divisions follow a rule that uses the smallest wall area going through the center of the cell. In other cases, however, cell division clearly deviates from this rule, which invariably leads to asymmetric cell division. By analyzing mutant embryos and through targeted genetic perturbation, we show that response to the hormone auxin triggers a deviation from the ``shortest wall'' rule. Our work demonstrates that a simple default rule couples division orientation to cell geometry in the embryo and that genetic regulation can create patterns by overriding the default rule.

Homogeneous reprocessing of GPS, GLONASS and SLR observations

The International GNSS Service (IGS) provides operational products for the GPS and GLONASS constellation. Homogeneously processed time series of parameters from the IGS are only available for GPS. Reprocessed GLONASS series are provided only by individual Analysis Centers (i. e. CODE and ESA), making it difficult to fully include the GLONASS system into a rigorous GNSS analysis. In view of the increasing number of active GLONASS satellites and a steadily growing number of GPS+GLONASS-tracking stations available over the past few years, Technische Universität Dresden, Technische Universität München, Universität Bern and Eidgenössische Technische Hochschule Zürich performed a combined reprocessing of GPS and GLONASS observations. Also, SLR observations to GPS and GLONASS are included in this reprocessing effort. Here, we show only SLR results from a GNSS orbit validation. In total, 18 years of data (1994–2011) have been processed from altogether 340 GNSS and 70 SLR stations. The use of GLONASS observations in addition to GPS has no impact on the estimated linear terrestrial reference frame parameters. However, daily station positions show an RMS reduction of 0.3 mm on average for the height component when additional GLONASS observations can be used for the time series determination. Analyzing satellite orbit overlaps, the rigorous combination of GPS and GLONASS neither improves nor degrades the GPS orbit precision. For GLONASS, however, the quality of the microwave-derived GLONASS orbits improves due to the combination. These findings are confirmed using independent SLR observations for a GNSS orbit validation. In comparison to previous studies, mean SLR biases for satellites GPS-35 and GPS-36 could be reduced in magnitude from −35 and −38 mm to −12 and −13 mm, respectively. Our results show that remaining SLR biases depend on the satellite type and the use of coated or uncoated retro-reflectors. For Earth rotation parameters, the increasing number of GLONASS satellites and tracking stations over the past few years leads to differences between GPS-only and GPS+GLONASS combined solutions which are most pronounced in the pole rate estimates with maximum 0.2 mas/day in magnitude. At the same time, the difference between GLONASS-only and combined solutions decreases. Derived GNSS orbits are used to estimate combined GPS+GLONASS satellite clocks, with first results presented in this paper. Phase observation residuals from a precise point positioning are at the level of 2 mm and particularly reveal poorly modeled yaw maneuver periods.

Contribution of Starlette, Stella, and AJISAI to the SLR-derived global reference frame

The contribution of Starlette, Stella, and AJI-SAI is currently neglected when defining the International Terrestrial Reference Frame, despite a long time series of precise SLR observations and a huge amount of available data. The inferior accuracy of the orbits of low orbiting geodetic satellites is the main reason for this neglect. The Analysis Centers of the International Laser Ranging Service (ILRS ACs) do, however, consider including low orbiting geodetic satellites for deriving the standard ILRS products based on LAGEOS and Etalon satellites, instead of the sparsely observed, and thus, virtually negligible Etalons. We process ten years of SLR observations to Starlette, Stella, AJISAI, and LAGEOS and we assess the impact of these Low Earth Orbiting (LEO) SLR satellites on the SLR-derived parameters. We study different orbit parameterizations, in particular different arc lengths and the impact of pseudo-stochastic pulses and dynamical orbit parameters on the quality of the solutions. We found that the repeatability of the East and North components of station coordinates, the quality of polar coordinates, and the scale estimates of the reference are improved when combining LAGEOS with low orbiting SLR satellites. In the multi-SLR solutions, the scale and the Z component of geocenter coordinates are less affected by deficiencies in solar radiation pressure modeling than in the LAGEOS-1/2 solutions, due to substantially reduced correlations between the Z geocenter coordinate and empirical orbit parameters. Eventually, we found that the standard values of Center-of-mass corrections (CoM) for geodetic LEO satellites are not valid for the currently operating SLR systems. The variations of station-dependent differential range biases reach 52 and 25 mm for AJISAI and Starlette/Stella, respectively, which is why estimating station dependent range biases or using station-dependent CoM, instead of one value for all SLR stations, is strongly recommended.This clearly indicates that the ILRS effort to produce CoM corrections for each satellite, which are site-specific and depend on the system characteristics at the time of tracking,is very important and needs to be implemented in the SLR data analysis.

Measurement of the neutrino velocity with the OPERA detector in the CNGS beam using the 2012 dedicated data

In spring 2012 CERN provided two weeks of a short bunch proton beam dedicated to the neutrino velocity measurement over a distance of 730 km. The OPERA neutrino experiment at the underground Gran Sasso Laboratory used an upgraded setup compared to the 2011 measurements, improving the measurement time accuracy. An independent timing system based on the Resistive Plate Chambers was exploited providing a time accuracy of ∼1 ns. Neutrino and anti-neutrino contributions were separated using the information provided by the OPERA magnetic spectrometers. The new analysis profited from the precision geodesy measurements of the neutrino baseline and of the CNGS/LNGS clock synchronization. The neutrino arrival time with respect to the one computed assuming the speed of light in vacuum is found to be δtν≡TOFc−TOFν=(0.6±0.4 (stat.)±3.0 (syst.)) ns and δtν¯≡TOFc−TOFν¯=(1.7±1.4 (stat.)±3.1 (syst.)) ns for νμ and ν¯μ, respectively. This corresponds to a limit on the muon neutrino velocity with respect to the speed of light of −1.8×10−6<(vν−c)/c<2.3×10−6 at 90% C.L. This new measurement confirms with higher accuracy the revised OPERA result.

Synthesis and cellular characterization of novel isoxazolo- and thiazolohydrazinylidene-chroman-2,4-diones on cancer and non-cancer cell growth and death

Coumarins are extensively studied anticoagulants that exert additional effects such as anticancerogenic and even anti-inflammatory. In order to find new drugs with anticancer activities, we report here the synthesis and the structural analysis of new coumarin derivatives which combine the coumarin core and five member heterocycles in hydrazinylidene-chroman-2,4-diones. The derivatives were prepared by derivatization of the appropriate heterocyclic amines which were used as electrophiles to attack the coumarin ring. The structures were characterized by spectroscopic techniques including IR, NMR, 2D-NMR and MS. These derivatives were further characterized especially in terms of a potential cytotoxic and apoptogenic effect in several cancer cell lines including the breast and prostate cancer cell lines MCF-7, MDA-MB-231, PC-3, LNCaP, and the monocytic leukemia cell line U937. Cell viability was determined after 48 h and 72 h of treatment with the novel compounds by MTT assay and the 50% inhibitory concentrations (EC50 values) were determined. Out of the 8 novel compounds screened for reduced cell viability, 4c, 4d and 4e were found to be the most promising and effective ones having EC50 values that were several fold reduced when compared to the reference substance 4-hydroxycoumarin. However, the effects were cancer cell line dependent. The breast cancer MDA-MB-231 cells, the prostate cancer LNCaP cells, and U937 cells were most sensitive, MCF-7 cells were less sensitive, and PC-3 cells were more resistant. Reduced cell viability was accompanied by increased apoptosis as shown by PARP-1 cleavage and reduced activity of the survival protein kinase Akt. In summary, this study has identified three novel coumarin derivatives that in comparison to 4-hydroxycoumarin have a higher efficiency to reduce cancer cell viability and trigger apoptosis and therefore may represent interesting novel drug candidates

Peripartal progesterone and prolactin have little effect on the rapid transport of immunoglobulin G into colostrum of dairy cows

Colostrum formation and lactogenesis in the mammary gland and the timing of parturition are regulated by endocrine signals. Changes in progesterone (P4) and prolactin (PRL) are considered key events that inhibit colostrum formation, trigger parturition, and signal the onset of lactation. The goal of our study was to determine if colostrum yield and composition and immunoglobulin transfer are affected by prepartum milking relative to the decrease in P4, peak of PRL, or occurrence of parturition. Twenty-three multiparous cows were randomly assigned to 1 of 2 groups: (1) control with first milking at 4h postcalving (CON, n=11), and (2) treatment group with first milking approximately 1d before calving and second milking at 4h after parturition (APM, n=12). Colostrum yields were recorded and proportional samples were analyzed for immunoglobulin G (IgG) concentration. Blood plasma samples for the analyses of P4 and PRL were collected 3 times daily at 8-h intervals for 4d prepartum and again taken at 4h after parturition. Total colostrum mass of APM cows was higher than that of CON cows. Immunoglobulin G concentration and protein content did not differ between antepartum milking in APM cows and postpartum milking in CON cows. Colostrum IgG concentration and protein content in APM cows at the postpartum milking were lower compared with the IgG concentration established at the prepartum (APM) and postpartum milkings of CON cows. Immunoglobulin G mass did not differ in first and second colostrum collection in APM cows but was lower compared with that of CON cows. The sum of IgG mass in APM cows (prepartum + postpartum collections) did not differ from that of CON cows. Lactose and fat in milk (concentration and mass) increased from first to second milking in APM cows. Total mass of lactose and fat in APM cows (prepartum + postpartum collections) was greater compared with that of CON cows. The finding that the time of milking relative to parturition, P4 decrease, and PRL peak slightly affected yield and quality of colostrum emphasizes the complex interactions of numerous endocrine and morphological changes occurring during colostrogenesis and lactogenesis in dairy cows. The considerably rapid transfer of immunoglobulins into colostrum of prepartum-milked cows within a few hours leads to the hypothesis that the transfer of IgG can be very fast and-contrary to earlier findings-persist at least until parturition.

Prevalence of potential retrograde embolization pathways in the proximal descending aorta in stroke patients and controls.

BACKGROUND Retrograde diastolic blood flow in the proximal descending aorta (DAo) connecting complex plaques (≥4 mm thick) with brain-supplying supra-aortic arteries may constitute a source of stroke. Yet, data only from high-risk populations (cryptogenic stroke patients with aortic atheroma≥3 mm) regarding the prevalence of this potential stroke mechanism are available. We aimed to quantify the frequency of this mechanism in unselected patients with cryptogenic stroke after routine diagnostics and controls without a history of stroke. METHODS 88 patients (67 stroke patients, 21 cardiac controls) were prospectively included. 3D T1-weighted bright blood MRI of the aorta was applied for the detection of complex DAo atheroma. ECG-triggered and navigator-gated 4D flow MRI allowed measuring time-resolved 3D blood flow in vivo. Potential retrograde embolization pathways were defined as the co-occurrence of complex plaques and retrograde blood flow in the DAo reaching the outlet of (a) the left subclavian artery, (b) the left common carotid artery, or/and (c) the brachiocephalic trunk. The frequency of these pathways was analyzed by importing 2D plaque images into 3D blood flow visualization software. RESULTS Complex DAo plaques were more frequent in stroke patients (44 in 31/67 patients (46.3%) vs. 5 in 4/21 controls (19.1%); p=0.039), especially in older patients (29/46 (63.04%) patients≥60 years of age with 41 plaques vs. 2/21 (9.14%) patients<60 years of age with 3 plaques; p<0.001). Contrary to our assumption, retrograde diastolic blood flow at the DAo occurred in every patient irrespective of the existence of plaques with a similar extent in both groups (26±14 vs. 32±18 mm; p=0.114). Therefore, only the higher prevalence of complex DAo plaques in stroke patients resulted in a three times higher frequency of potential retrograde embolization pathways compared to controls (22/67 (32.8%) vs. 2/21 (9.5%) controls; p=0.048). CONCLUSIONS This study revealed that retrograde flow in the descending aorta is a common phenomenon not only in stroke patients. The existence of potential retrograde embolization pathways depends mainly on the occurrence of complex plaques in the area 0 to ∼30 mm behind the outlet of the left subclavian artery, which is exposed to flow reversal. In conclusion, we have shown that the frequency of potential retrograde embolization pathways was significantly higher in stroke patients suggesting that this mechanism may play a role in retrograde brain embolism.

Comparison of GOCE-GPS gravity fields derived by different approaches

Several techniques have been proposed to exploit GNSS-derived kinematic orbit information for the determination of long-wavelength gravity field features. These methods include the (i) celestial mechanics approach, (ii) short-arc approach, (iii) point-wise acceleration approach, (iv) averaged acceleration approach, and (v) energy balance approach. Although there is a general consensus that—except for energy balance—these methods theoretically provide equivalent results, real data gravity field solutions from kinematic orbit analysis have never been evaluated against each other within a consistent data processing environment. This contribution strives to close this gap. Target consistency criteria for our study are the input data sets, period of investigation, spherical harmonic resolution, a priori gravity field information, etc. We compare GOCE gravity field estimates based on the aforementioned approaches as computed at the Graz University of Technology, the University of Bern, the University of Stuttgart/Austrian Academy of Sciences, and by RHEA Systems for the European Space Agency. The involved research groups complied with most of the consistency criterions. Deviations only occur where technical unfeasibility exists. Performance measures include formal errors, differences with respect to a state-of-the-art GRACE gravity field, (cumulative) geoid height differences, and SLR residuals from precise orbit determination of geodetic satellites. We found that for the approaches (i) to (iv), the cumulative geoid height differences at spherical harmonic degree 100 differ by only ≈10 % ; in the absence of the polar data gap, SLR residuals agree by ≈96 % . From our investigations, we conclude that real data analysis results are in agreement with the theoretical considerations concerning the (relative) performance of the different approaches.