Computational fluid dynamicaccuracy in mimicking changes in blood hemodynamics in patients with acute type IIIb aortic dissection treated with TEVAR

Background: We aimed to verify the accuracy of the Computational Fluid Dynamics (CFD) algorithm for blood flow reconstruction for type IIIb aortic dissection (TBAD) before and after thoracic endovascular aortic repair (TEVAR). Methods: We made 3D models of the aorta and its branches using pre- and post-operative CT data from five patients treated for TBAD. The CFD technique was used to quantify the displacement forces acting on the aortic wall in the areas of endograft, mass flow rate/velocity and wall shear stress (WSS). Calculated results were verified with ultrasonography (USG-Doppler) data. Results: CFD results indicated that the TEVAR procedure caused a 7-fold improvement in overall blood flow through the aorta (p = 0.0001), which is in line with USG-Doppler data. A comparison of CFD results and USG-Doppler data indicated no significant change in blood flow through the analysed arteries. CFD also showed a significant increase in flow rate for thoracic trunk and renal arteries, which was in accordance with USG-Doppler data (accuracy 90% and 99.9%). Moreover, we observed a significant decrease in WSS values within the whole aorta after TEVAR compared to pre-TEVAR (1.34 ± 0.20 Pa vs. 3.80 ± 0.59 Pa, respectively, p = 0.0001). This decrease was shown by a significant reduction in WSS and WSS contours in the thoracic aorta (from 3.10 ± 0.27 Pa to 1.34 ± 0.11Pa, p = 0.043) and renal arteries (from 4.40 ± 0.25 Pa to 1.50 ± 0.22 Pa p = 0.043). Conclusions: Post-operative remodelling of the aorta after TEVAR for TBAD improved hemodynamic patterns reflected by flow, velocity and WSS with an accuracy of 99%

The GFZ GRACE RL06 Monthly Gravity Field Time Series: Processing Details and Quality Assessment

Time-variable gravity field models derived from observations of the Gravity Recovery and Climate Experiment (GRACE) mission, whose science operations phase ended in June 2017 after more than 15 years, enabled a multitude of studies of Earth’s surface mass transport processes and climate change. The German Research Centre for Geosciences (GFZ), routinely processing such monthly gravity fields as part of the GRACE Science Data System, has reprocessed the complete GRACE mission and released an improved GFZ GRACE RL06 monthly gravity field time series. This study provides an insight into the processing strategy of GFZ RL06 which has been considerably changed with respect to previous GFZ GRACE releases, and modifications relative to the precursor GFZ RL05a are described. The quality of the RL06 gravity field models is analyzed and discussed both in the spectral and spatial domain in comparison to the RL05a time series. All results indicate significant improvements of about 40% in terms of reduced noise. It is also shown that the GFZ RL06 time series is a step forward in terms of consistency, and that errors of the gravity field coefficients are more realistic. These findings are confirmed as well by independent validation of the monthly GRACE models, as done in this work by means of ocean bottom pressure in situ observations and orbit tests with the GOCE satellite. Thus, the GFZ GRACE RL06 time series allows for a better quantification of mass changes in the Earth system.DFG, FOR 2736, New Refined Observations of Climate Change from Spaceborne Gravity Missions (NEROGRAV)BMBF, 03F0654A, GRACE-FO - Projektmanagement, Aufbau eines wissenschaftlichen Auswertesystems und Aufbau eines GRACE-FO Projektbüro

Simvastatin attenuates abdominal aortic aneurysm formation favoured by lack of Nrf2 transcriptional activity

Surgical intervention is currently the only option for an abdominal aortic aneurysm (AAA), preventing its rupture and sudden death of a patient. Therefore, it is crucial to determine the pathogenic mechanisms of this disease for the development of effective pharmacological therapies. Oxidative stress is said to be one of the pivotal factors in the pathogenesis of AAAs. Thus, we aimed to evaluate the significance of nuclear factor erythroid 2-related factor 2 (Nrf2) transcriptional activity in the development of AAA and to verify if simvastatin, administered as pre- and cotreatment, may counteract this structural malformation. Experiments were performed on mice with inhibited transcriptional activity of Nrf2 (tKO) and wild-type (WT) counterparts. We used a model of angiotensin II- (AngII-) induced AAA, combined with a fat-enriched diet. Mice were administered with AngII or saline for up to 28 days via osmotic minipumps. Simvastatin administration was started 7 days before the osmotic pump placement and then continued until the end of the experiment. We found that Nrf2 inactivation increased the risk of development and rupture of AAA. Importantly, these effects were reversed by simvastatin in tKO mice, but not in WT. The abrupt blood pressure rise induced by AngII was mitigated in simvastatin-treated animals regardless of the genotype. Simvastatin-affected parameters that differed between the healthy structure of the aorta and aneurysmal tissue included immune cell infiltration of the aortic wall, VCAM1 mRNA and protein level, extracellular matrix degradation, TGF-β1 mRNA level, and ERK phosphorylation, but neither oxidative stress nor the level of Angiotensin II Type 1 Receptor (AT1R). Taken together, the inhibition of Nrf2 transcriptional activity facilitates AAA formation in mice, which can be prevented by simvastatin. It suggests that statin treatment of patients with hypercholesterolemia might have not only a beneficial effect in terms of controlling atherosclerosis but also potential AAA prevention

Phase separation drives X-chromosome inactivation: a hypothesis

The long non-coding RNA Xist induces heterochromatinization of the X chromosome by recruiting repressive protein complexes to chromatin. Here we gather evidence, from the literature and from computational analyses, showing that Xist assemblies are similar in size, shape and composition to phase-separated condensates, such as paraspeckles and stress granules. Given the progressive sequestration of Xist’s binding partners during X-chromosome inactivation, we formulate the hypothesis that Xist uses phase separation to perform its function

Signal-in-Space Range Error Analysis of the Simulated Broadcast Ephemerides for the Kepler System.

Kepler navigation system is a DLR’s proposal for the next generation of GNSS. It comprises a constellation of Galileo-like satellites augmented by Low Earth Orbit (LEO) satellites and exploits optical inter-satellite links (OISLs) for constellation-wide clock synchronization, communication and precise ranging. In our previous works we analyzed extensively precise orbit determination (POD) performance of this system. We simulated various Kepler scenarios, and the POD results were compared to the baseline Galileo scenario. We demonstrated, that Kepler precise orbits can achieve sub-cm Signal in Space Range Errors (SiSREs) compared to few cm for Galileo. However, precise orbits – based on measurement data, are only available with substantial delay and cannot be used for real-time navigation directly. Operational GNSS provides predicted orbits and clock offsets which are distributed in the navigation message for user positioning. Thus, we extended our POD system with prediction and generation of navigation messages. In this contribution, we focus on the analysis of orbit, clock and Earth rotation parameter (ERP) prediction errors for Galileo and selected Kepler scenarios. The Galileo clocks were simulated using a model for Passive Hydrogen Masers with a stability and drift consistent with the precise clocks estimated by the Center for Orbit Determination in Europe (CODE). For the Kepler system, the clocks are assumed to be synchronized and were simulated as null value with a Gaussian noise of 3-10 ps (1-3 mm). The Galileo F/NAV broadcast ephemeris model, which consists of 15 orbital parameters, is used for our analysis. The parameters were fitted to the predicted orbits with a least-squares adjustment and truncated in the navigation message according to the number of bits allocated to each parameter. The clock prediction model consists of a constant and a drift term obtained from linear fit to the clocks estimated in POD. The accuracy of the predicted orbits and clocks found depends on the constellation, POD modelling errors and the propagation interval. In our analysis, we considered scenarios with perfect models and, for more realistic results, with a number of modeling errors introduced in the POD. For all analyzed cases we report global average Signal in Space Range Error (SiSRE) which accounts for orbit and clock errors and is a key performance indicator of a navigation system. Our simulations show, that the Galileo system is capable of providing broadcast data with SiSRE at a dm level, consistent with 1-2 dm SiSRE for the actual broadcast data. For the Kepler system the clocks are synchronized with 1-3 mm precision and there are no additional clock prediction errors. The orbit prediction errors can be well below 1 cm due the exploitation of precise intersatellite ranges. However, the accuracy of predicted Earth rotation parameters (ERPs), which are used in transformation of the orbits from the Earth-Center-Inertial (ECI) to Earth-Centered Earth-Fixed frame (ECEF), have a significant impact on the accuracy of the predicted orbits in ECEF. Currently, we have implemented in our prediction system a simple linear extrapolation of ERPs based on values estimated in POD. We found, that this introduces significant errors in the orbit cross- and along-track direction, increasing the SiSRE by up to a decimeter after 24 h. Therefore, precise modelling and prediction of ERPs is an important factor for achieving sub-cm SiSRE for the Kepler system. We identified two other parameters, GNSS ionosphere-free pseudo-range hardware delays (HDs) and antenna radial phase center offsets (PCOs), that are relevant for SiSRE. For Galileo, they are not critical since HDs and most of the PCO error are absorbed by the estimated satellite clocks and, if assumed stable, do not degrade the accuracy of the clock prediction. For Kepler, where clocks are synchronized in the optical domain and are not estimated in POD, errors of these parameters directly affect SiSRE and must be precisely calibrated. We analyzed also in details the impact of broadcast parameter fit interval length, varying from 10 minutes to 4 h, and parameter truncation on the accuracy of reconstructed orbits and SiSRE. We found, that the maximum orbit fit error for intervals up to 2 h contributes to SiSRE at few mm level, while the fit interval of 4 h can increase SiSRE by a decimeter. The parameter truncation errors are not dependent on the fitting interval and increase SiSRE by an average of 1 cm and maximum of 3 cm. Such errors can be seen as a SiSRE limiting factor for highly accurate Kepler orbits (below 1 cm) and need to be mitigated, e.g. by allocation of more bits to most relevant parameters. Finally, we concluded that SiSRE below 1 cm can be continuously achieved for the Kepler system, which is at least an order of magnitude smaller than for Galileo. However, this requires precisely calibrated GNSS hardware delays and antenna phase center offsets

Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment

Abstract Background Neutrophil gelatinase-associated lipocalin (NGAL), an acute phase protein released by neutrophils, has been described as biomarker of inflammatory states. Type 2 diabetes mellitus (T2DM) is characterized by increased inflammation and an elevated risk for embolization of carotid artery stenosis (CAS). We aimed to explore the role of NGAL systemically and in plaques of diabetics undergoing carotid endarterectomy. Moreover, the potential anti-inflammatory effect of metformin on NGAL was addressed in diabetics. Methods Serum NGAL and matrix metalloproteinase (MMP)-9/NGAL levels were measured in 136 patients (67 with T2DM vs. 69 non-diabetics) by specific ELISA. Endarterectomy samples were graded histologically according to the American Heart Association´s classification. NGAL mRNA expression was detected using RealTime-PCR in carotid endarterectomy specimens. Results Serum NGAL [median 107.4 ng/ml (quartiles: 75.2–145.0) vs. 64.4 (50.4 –81.3), p < 0.0001] and MMP-9/NGAL [41.5 ng/ml (20.8–63.9) vs. 27.6 (16.0–42.4), p = 0.017] were significantly elevated in diabetics compared to non-diabetics, as were leukocytes, neutrophils, C-reactive protein and fibrinogen (all p < 0.05). In patients with symptomatic and asymptomatic CAS diabetics had higher NGAL levels compared to non-diabetics [128.8 ng/ml (100.8–195.6) vs. 64.8 (48.9–82.2] and [101.6 ng/ml (70.1–125.3) vs. 63.8 (51.0–81.3), respectively, both p < 0.0001]. Presence of T2DM and type VI plaques (with surface defect, hemorrhage or thrombus) had a profound impact on NGAL levels (both p < 0.01) in multiple linear regression analysis. NGAL mRNA was detectable in 95% of analyzed carotid artery lesions of diabetics compared to 5% of non-diabetics (p < 0.0001). Accordingly, cerebral embolization was more frequent in diabetics (52.2% vs. 29%, p = 0.006). Metformin treatment was associated with decreased NGAL [60.7 ng/ml (51.9–69.2) vs. 121.7 (103.7–169.9), p < 0.0001] and MMP-9/NGAL [20.8 ng/ml (12.1–26.5) vs. 53.7 (27.4–73.4), p = 0.007] in diabetics and reduced leukocyte infiltration in carotid lesions of diabetics. Conclusions Higher NGAL levels in serum and plaques are associated with T2DM in patients with CAS. Metformin significantly reduced the inflammatory burden including NGAL in diabetics. Early treatment of these patients may be recommended, as elevated NGAL levels were linked with vulnerable plaques prone for embolization

Lower levels of Caveolin-1 and higher levels of endothelial nitric oxide synthase are observed in abdominal aortic aneurysm patients treated with simvastatin

This study was undertaken to verify whether simvastatin modulates Cav-1/eNOS expression, and if this modulation is associated with changes in pro- and anti-inflammatory cytokine and Toll-like receptor 4 (TLR4) level in abdominal aortic aneurysm (AAA). It is a 1:2 case-control study of non-statin (n=12) and simvastatin-treated patients (n=24) who underwent open AAA repair. Simvastatin treatment decreased Cav-1 (p0.05) and increased IL-10 concentration (p=0.055); however, TLR4 expression was unaffected, suggesting that simvastatin influences Cav-1 and eNOS in the AAA wall by other mechanisms. Simvastatin may modulate Cav-1 and eNOS expression in the aneurysmal wall, indicating a potentially beneficial role for statins in AAA patients

Separation of Recollision Mechanisms in Nonsequential Strong Field Double Ionization of Ar: The Role of Excitation Tunneling

Vector momentum distributions of two electrons created in double ionization of Ar by 25 fs, 0.25PW/cm2 laser pulses at 795 nm have been measured using a “reaction microscope.” At this intensity, where nonsequential ionization dominates, distinct correlation patterns are observed in the two-electron momentum distributions. A kinematical analysis of these spectra within the classical “recollision model” revealed an (e,2e)-like process and excitation with subsequent tunneling of the second electron as two different ionization mechanisms. This allows a qualitative separation of the two mechanisms demonstrating that excitation-tunneling is the dominant contribution to the total double ionization yield

Non-Sequential Double Ionization of Ne in Intense Laser Pulses: A Coincidence Experiment

The dynamics of Neon double ionization by 25 fs, 1.0 PW/cm2 laser pulses at 795 nm has been studied in a many particle coincidence experiment. The momentum vectors of all ejected atomic fragments (electrons and ions) have been measured using combined electron and recoil-ion momentum spectroscopy. Electron emission spectra for double and single ionization will be discussed. In both processes the mean electron energies differ considerably and high energetic electrons with energies of more than 120 eV have been observed for double ionization. The experimental results are in qualitative agreement with the rescattering model