Simulated and observed horizontal inhomogeneities of optical thickness of Arctic stratus

Two-dimensional horizontal fields of cloud optical thickness τ derived from airborne measurements of solar spectral, cloud-reflected radiance are compared with semi-idealized large eddy simulations (LESs) of Arctic stratus performed with the Consortium for Small-scale Modeling (COSMO) atmospheric model. The measurements were collected during the Vertical Distribution of Ice in Arctic Clouds (VERDI) campaign carried out in Inuvik, Canada, in April/May 2012. The input for the LESs is obtained from collocated airborne dropsonde observations of a persistent Arctic stratus above the sea-ice-free Beaufort Sea. Simulations are performed for spatial resolutions of 50m (1.6km × 1.6km domain) and 100m (6.4km × 6.4km domain). Macrophysical cloud properties, such as cloud top altitude and vertical extent, are well captured by the COSMO simulations. However, COSMO produces rather homogeneous clouds compared to the measurements, in particular for the simulations with coarser spatial resolution. For both spatial resolutions, the directional structure of the cloud inhomogeneity is well represented by the model. Differences between the individual cases are mainly associated with the wind shear near cloud top and the vertical structure of the atmospheric boundary layer. A sensitivity study changing the wind velocity in COSMO by a vertically constant scaling factor shows that the directional, small-scale cloud inhomogeneity structures can range from 250 to 800m, depending on the mean wind speed, if the simulated domain is large enough to capture also large-scale structures, which then influence the small-scale structures. For those cases, a threshold wind velocity is identified, which determines when the cloud inhomogeneity stops increasing with increasing wind velocity

Steric exclusion chromatography for the purification of recombinant baculovirus

Steric exclusion chromatography (SXC) has already proven to be a valuable tool in the purification of proteins and virus particles. An important benefit of the method is the fast and simple procedure at mild chromatography conditions as no harsh binding and elution buffers are needed. The sample is initially mixed with a polyethylene glycol (PEG) containing buffer of choice. The steric exclusion of a macromolecule from the polyethylene glycol and the stationary phase allows a selective retention of the product, depending, among others, mainly on its size as well as on the molecular weight and concentration of the PEG. Here, SXC was set up in order that smaller process contaminants, i.e. host cell proteins and DNA, did not bind to the stationary phase, in contrast to the targeted larger virus particles. These were subsequently eluted reducing the PEG concentration in the mobile phase. Regenerated cellulose was used as stationary phase to purify VSV-G pseudotyped AcMNPV baculoviruses derived from Spodoptera frugiperda cells (Sf9 cells) by SXC. The purified virus particles are used as gene transfer tools for human mesenchymal stroma cells. For this purpose, the baculovirus was clarified prior to the SXC by sequential centrifugation (4700 gmax). The SXC conditions were optimized in terms of yield and purity by a design of experiment approach considering the PEG molecular weight, its concentration and the ionic strength of the elution buffer as critical process parameters. Within the design space virus recovery was ≥70%. Without further nuclease treatment the depletion of double-stranded DNA was \u3e90% and the amount of host cell proteins were reduced \u3e90% in the virus fraction. In conclusion, SXC can drastically reduce the process development in terms of time and equipment requirements for the purification of recombinant baculoviruses, as well as for the achieved purity which is superior over classical methods

Intercellular Friction and Motility Drive Orientational Order in Cell Monolayers

Spatiotemporal patterns in multicellular systems are important to understanding tissue dynamics, for instance, during embryonic development and disease. Here, we use a multiphase field model to study numerically the behavior of a near-confluent monolayer of deformable cells with intercellular friction. Varying friction and cell motility drives a solid-liquid transition, and near the transition boundary, we find the emergence of nematic order of cell deformation driven by shear-aligning cellular flows. Intercellular friction endows the monolayer with a finite viscosity, which significantly increases the spatial correlation in the flow and, concomitantly, the extent of nematic order. We also show that hexatic and nematic order are tightly coupled and propose a mechanical-geometric model for the colocalization of +1/2 nematic defects and 5-7 disclination pairs, which are the structural defects in the hexatic phase. Such topological defects coincide with regions of high cell-cell overlap, suggesting that they may mediate cellular extrusion from the monolayer, as found experimentally. Our results delineate a mechanical basis for the recent observation of nematic and hexatic order in multicellular collectives in experiments and simulations and pinpoint a generic pathway to couple topological and physical effects in these systems

Acute type A aortic dissection and pregnancy: a population-based study

Objective: Pregnancy has been reported to be an independent risk factor for 50% of acute aortic dissections recorded in women younger than 45 years of age. The present epidemiologic study aimed to identify whether this putative association of pregnancy and acute type A dissection could be an artifact of selective reporting. Methods: This population-based study was conducted in the City of Vienna, Austria, Europe, in an average female population of 341381 women in the age range of 15-45 years who were followed up between 1994 and 2004 (total of 3755.195 person-years of observation). During this study, the incidence, management, and outcome of acute type A dissection were determined. Results: Fifteen patients (mean age: 38.8 years, SD: 4.8) with acute aortic dissection were identified, and an overall incidence of 0.4 case per 100000 person-years was estimated. The prehospital mortality rate was recorded to be 53%. Six patients, including two women in late pregnancy (incidence: 0.05 cases per 100000 person-years), were treated successfully by surgical repair during deep hypothermic circulatory arrest (in-hospital mortality rate: 6.6%). Pregnancy and aortic dissection were identified as events that were not related (RR: 3.27; 95% confidence interval (CI): 0.82-12.95; P=0.14). Observation during long-term follow-up was uneventful. Conclusions: Acute aortic dissection represents a rare pathology in women younger than 45 years of age; however, it is associated with a high rate of sudden death. Pregnancy may not be a risk factor for this life-threatening vascular emergency. Immediate referral to surgery, even during pregnancy, will result in a prognosis of favorable outcom

Granulation of snow: From tumbler experiments to discrete element simulations

It is well known that snow avalanches exhibit granulation phenomena, i.e., the formation of large and apparently stable snow granules during the flow. The size distribution of the granules has an influence on flow behavior which, in turn, affects runout distances and avalanche velocities. The underlying mechanisms of granule formation are notoriously difficult to investigate within large-scale field experiments, due to limitations in the scope for measuring temperatures, velocities, and size distributions. To address this issue we present experiments with a concrete tumbler, which provide an appropriate means to investigate granule formation of snow. In a set of experiments at constant rotation velocity with varying temperatures and water content, we demonstrate that temperature has a major impact on the formation of granules. The experiments showed that granules only formed when the snow temperature exceeded -1(degrees)C. No evolution in the granule size was observed at colder temperatures. Depending on the conditions, different granulation regimes are obtained, which are qualitatively classified according to their persistence and size distribution. The potential of granulation of snow in a tumbler is further demonstrated by showing that generic features of the experiments can be reproduced by cohesive discrete element simulations. The proposed discrete element model mimics the competition between cohesive forces, which promote aggregation, and impact forces, which induce fragmentation, and supports the interpretation of the granule regime classification obtained from the tumbler experiments. Generalizations, implications for flow dynamics, and experimental and model limitations as well as suggestions for future work are discussed

In Silico TRials guide optimal stratification of ATrIal FIbrillation patients to Catheter Ablation and pharmacological medicaTION: the i-STRATIFICATION study

Aims: Patients with persistent atrial fibrillation (AF) experience 50% recurrence despite pulmonary vein isolation (PVI), and no consensus is established for secondary treatments. The aim of our i-STRATIFICATION study is to provide evidence for stratifying patients with AF recurrence after PVI to optimal pharmacological and ablation therapies, through in silico trials. Methods and results: A cohort of 800 virtual patients, with variability in atrial anatomy, electrophysiology, and tissue structure (low-voltage areas, LVAs), was developed and validated against clinical data from ionic currents to electrocardiogram. Virtual patients presenting AF post-PVI underwent 12 secondary treatments. Sustained AF developed in 522 virtual patients after PVI. Second ablation procedures involving left atrial ablation alone showed 55% efficacy, only succeeding in the small right atria (<60 mL). When additional cavo-tricuspid isthmus ablation was considered, Marshall-PLAN sufficed (66% efficacy) for the small left atria (<90 mL). For the bigger left atria, a more aggressive ablation approach was required, such as anterior mitral line (75% efficacy) or posterior wall isolation plus mitral isthmus ablation (77% efficacy). Virtual patients with LVAs greatly benefited from LVA ablation in the left and right atria (100% efficacy). Conversely, in the absence of LVAs, synergistic ablation and pharmacotherapy could terminate AF. In the absence of ablation, the patient’s ionic current substrate modulated the response to antiarrhythmic drugs, being the inward currents critical for optimal stratification to amiodarone or vernakalant. Conclusion: In silico trials identify optimal strategies for AF treatment based on virtual patient characteristics, evidencing the power of human modelling and simulation as a clinical assisting tool

SuLMaSS - Sustainable Lifecycle Management for Scientific Software

The SuLMaSS project [1] will advance, develop, build, evaluate, and test infrastructure for sustainable lifecycle management of scientific software. The infrastructure is tested and evaluated by an existing cardiac electrophysiology simulation software project, which is currently in the prototype state and will be advanced towards optimal usability and a large and active user community. Thus, SuLMaSS is focused on designing and implementing application-oriented e-research technologies and the impact is three-fold: - Provision of a high quality, user-friendly cardiac electrophysiology simulation software package that accommodates attestable needs of the scientific community. - Delivery of infrastructure components for testing, safe-keeping, referencing, and versioning of all phases of the lifecycle of scientific software. - Serve as a best practice example for sustainable scientific software management. Scientific software development in Germany and beyond shall benefit through both the aforementioned best practice role model and the advanced infrastructure that will, in part, be available for external projects as well. With adding value for the wider scientific cardiac electrophysiology community, the software will be available under an open source license and be provided for a large share of people and research groups that can potentially leverage computational cardiac modeling methods. Institutional infrastructure will be extended to explore, evaluate and establish the basis for research software development regarding testing, usage, maintenance and support. The cardiac electrophysiology simulator will drive and showcase the infrastructure formation, thus serving as a lighthouse project. The developed infrastructure can be used by other scientific software projects in future and aims to support the full research lifecycle from exploration through conclusive analysis and publication, to archival, and sharing of data and source code, thus increasing the quality of research results. Moreover it will foster a community-based collaborative development and improve sustainability of research software. References: [1]­‌‌‌‌‌‌‌‌‌ http://www.dfg.de/dfg_magazin/aus_der_wissenschaft/impulse_fuer_das_digitale_lis_jb17/02_aus_der_foerderung/index.htm

Prognostic value of baseline imaging and clinical features in patients with advanced hepatocellular carcinoma

AIMS To investigate the prognostic value of baseline imaging features for overall survival (OS) and liver decompensation (LD) in patients with hepatocellular carcinoma (HCC). DESIGN Patients with advanced HCC from the SORAMIC trial were evaluated in this post hoc analysis. Several radiological imaging features were collected from baseline computed tomography (CT) and magnetic resonance imaging (MRI) imaging, besides clinical values. The prognostic value of these features for OS and LD (grade 2 bilirubin increase) was quantified with univariate Cox proportional hazard models and multivariate Least Absolute Shrinkage and Selection Operator (LASSO) regression. RESULTS Three hundred and seventy-six patients were included in this study. The treatment arm was not correlated with OS. LASSO showed satellite lesions, atypical HCC, peritumoral arterial enhancement, larger tumour size, higher albumin-bilirubin (ALBI) score, liver-spleen ratio <1.5, ascites, pleural effusion and higher bilirubin values were predictors of worse OS, and higher relative liver enhancement, smooth margin and capsule were associated with better OS. LASSO analysis for LD showed satellite lesions, peritumoral hypointensity in hepatobiliary phase, high ALBI score, higher bilirubin values and ascites were predictors of LD, while randomisation to sorafenib arm was associated with lower LD. CONCLUSIONS Imaging features showing aggressive tumour biology and poor liver function, in addition to clinical parameters, can serve as imaging biomarkers for OS and LD in patients receiving sorafenib and selective internal radiation therapy for HCC

Thyroid-Hormone–Disrupting Chemicals: Evidence for Dose-Dependent Additivity or Synergism

Endocrine disruption from environmental contaminants has been linked to a broad spectrum of adverse outcomes. One concern about endocrine-disrupting xenobiotics is the potential for additive or synergistic (i.e., greater-than-additive) effects of mixtures. A short-term dosing model to examine the effects of environmental mixtures on thyroid homeostasis has been developed. Prototypic thyroid-disrupting chemicals (TDCs) such as dioxins, polychlorinated biphenyls (PCBs), and poly-brominated diphenyl ethers have been shown to alter thyroid hormone homeostasis in this model primarily by up-regulating hepatic catabolism of thyroid hormones via at least two mechanisms. Our present effort tested the hypothesis that a mixture of TDCs will affect serum total thyroxine (T(4)) concentrations in a dose-additive manner. Young female Long-Evans rats were dosed via gavage with 18 different polyyhalogenated aromatic hydrocarbons [2 dioxins, 4 dibenzofurans, and 12 PCBs, including dioxin-like and non-dioxin-like PCBs] for 4 consecutive days. Serum total T(4) was measured via radioimmunoassay in samples collected 24 hr after the last dose. Extensive dose–response functions (based on seven to nine doses per chemical) were determined for individual chemicals. A mixture was custom synthesized with the ratio of chemicals based on environmental concentrations. Serial dilutions of this mixture ranged from approximately background levels to 100-fold greater than background human daily intakes. Six serial dilutions of the mixture were tested in the same 4-day assay. Doses of individual chemicals that were associated with a 30% TH decrease from control (ED(30)), as well as predicted mixture outcomes were calculated using a flexible single-chemical-required method applicable to chemicals with differing dose thresholds and maximum-effect asymptotes. The single-chemical data were modeled without and with the mixture data to determine, respectively, the expected mixture response (the additivity model) and the experimentally observed mixture response (the empirical model). A likelihood-ratio test revealed statistically significant departure from dose additivity. There was no deviation from additivity at the lowest doses of the mixture, but there was a greater-than-additive effect at the three highest mixtures doses. At high doses the additivity model underpredicted the empirical effects by 2- to 3-fold. These are the first results to suggest dose-dependent additivity and synergism in TDCs that may act via different mechanisms in a complex mixture. The results imply that cumulative risk approaches be considered when assessing the risk of exposure to chemical mixtures that contain TDCs