Learning stable and predictive structures in kinetic systems: Benefits of a causal approach

Learning kinetic systems from data is one of the core challenges in many fields. Identifying stable models is essential for the generalization capabilities of data-driven inference. We introduce a computationally efficient framework, called CausalKinetiX, that identifies structure from discrete time, noisy observations, generated from heterogeneous experiments. The algorithm assumes the existence of an underlying, invariant kinetic model, a key criterion for reproducible research. Results on both simulated and real-world examples suggest that learning the structure of kinetic systems benefits from a causal perspective. The identified variables and models allow for a concise description of the dynamics across multiple experimental settings and can be used for prediction in unseen experiments. We observe significant improvements compared to well established approaches focusing solely on predictive performance, especially for out-of-sample generalization

The prevalence of orthorexia in exercising populations: a systematic review and meta-analysis

Aim Orthorexia Nervosa (ON) describes a pathological obsession with proper and high-quality nutrition that is necessary to research further in order to elucidate its prevalence and correlates which may bear implications for prevention and treatment. The aim of this study was to review studies that report the prevalence of ON in people who exercise, calculate an overall prevalence through a random-effects meta-analysis approach and investigate the association of ON prevalence using a random-effects meta-regression. In addition, a sub-group-analysis based on ON-instruments and a sensitivity analysis excluding students samples, were conducted. Method Systematic searches were conducted in the following online databases: PubMed, Embase, Web of Science, PsychInfo, CINAHL, Google Scholar and OpenNet. The following search terms were used: Orthore* AND (prevalenc* OR incidenc* OR frequen* OR cut-off OR epidem*). A total of 613 unique hits were reviewed by two blinded authors, and 24 studies were coded and assessed for risk of bias (Holy et.al). The meta-regression included three independent variables (sex, type of sport, and sample size). Results The overall prevalence of ON in the exercising population was 55.3% (95% CI 43.2–66.8). Cochran’s Q was 11,436.38 (df = 23, p < 0.0000), and the I2 was 98.4%, indicating high heterogeneity across studies. The sensitivity showed an overall prevalence of 51.3% (95% CI 51.3–70.0). There was a significant difference in prevalence estimates based on the instruments used (Qbet = 33.6, df = 2, p < 0.01). Discussion The overall prevalence of ON in exercising populations was very high. The between-study disparity was large and was partly explained by the ON-instrument administered. One fourth of the studies had a moderate risk of bias. The majority of the studies did not specify relevant demographic information about the sample, and information about the type of sport was frequently missing.publishedVersio

DNA origami nanorulers and emerging reference structures

The DNA origami technique itself is considered a milestone of DNA nanotechnology and DNA origami nanorulers represent the first widespread application of this technique. DNA origami nanorulers are used to demonstrate the capabilities of techniques and are valuable training samples. They have meanwhile been developed for a multitude of microscopy methods including optical microscopy, atomic force microscopy, and electron microscopy, and their unique properties are further exploited to develop point-light sources, brightness references, nanophotonic test structures, and alignment tools for correlative microscopy. In this perspective, we provide an overview of the basics of DNA origami nanorulers and their increasing applications in fields of optical and especially super-resolution fluorescence microscopy. In addition, emerging applications of reference structures based on DNA origami are discussed together with recent developments

PHASING OUT FOSSIL GAS STEAM GENERATORS: Demand-based generation of process steam from thermally stored renewable energy with the Rotating Drum Heat Exchanger

By utilizing the phase change enthalpy as well as the thermal energy that can be stored during a temperature change, the storage density of typically used nitrate salts can be raised up to 330 KWh*m-3, which is an increase of 60 % compared to state-of-the-art two-tank molten salt storages. The Rotating Drum Heat Exchanger recently developed by the authors is predestined for the evaporation of water while transferring thermal energy from a nitrate salt. Thereby, a horizontally mounted rotating drum is partially immersed in liquid nitrate salt. While water evaporates inside the drum, the liquid nitrate salt solidifies at the outer surface, transferring both sensible heat and latent heat of the nitrate salt. The solidified nitrate salt is removed from the surface of the drum by a stationary scraper, which enables the separation of the liquid and solid phase of the storage material. This results in a complete separation of the thermal power and thermal capacity of a storage system based on the Rotating Drum Heat Exchanger. Numerical simulations indicate a surface-specific heat transfer density of up to 200 KW*m-2 when sodium nitrate is used as storage material and saturated stream is generated at a pressure of 20 bar. While the technology of the Rotating Drum Heat Exchanger has been experimentally proved for low-temperature application, a high-temperature prototype for high-pressure steam generation is currently under development. In addition to the current progress on the prototype, the presentation will describe and discuss a freely scalable design of the Rotating Drum Heat Exchanger for steam generation in the megawatt range. The heat exchanger is thereby integrated into an entire thermal energy storage system, which also enables the cogeneration of electricity and the flexibilization of current steam supply systems. The use of a phase change material also allows the integration of high-temperature heat pumps

Demand orientated steam generation from phase change material by using a rotating drum heat exchanger

INTRODUCTION: During the discharge process of a latent heat storage, phase change material solidifies at the heat transfer surface, which decreases the heat transfer. In the presented rotating drum heat exchanger for latent heat storage a rotating drum is partially immersed in liquid phase change material. While water evaporates as it passes through the drum, the liquid phase change material solidifies at the outer surface of the drum. The solidified layer is removed by a fixed scraper at each rotation and the solid phase change material is stored in a separate tank. This leads to a high surface specific heat transfer and a separation of power and capacity. In the presentation, a complete heat storage system based on a rotating drum heat exchanger and sodium nitrate as phase change material for the demand-oriented generation of steam for industrial processes as well as for electrical power generation is discussed based on theoretical and experimental research conducted with a laboratory pilot of the rotating drum heat exchanger. METHODS: Three different designs of the drum are discussed: a drum completely filled with water, a drum with concentric annular gap and a drum with several individual tubes drilled into the drum wall. The concepts are examined analytically and numerically with respect to heat transfer capacity, maximum operating parameters and technical feasibility. RESULTS: While a drum completely filled with water is predestined for the generation of low-pressure saturated steam for industrial processes, superheated steam can be reached with a concentric gap. High�pressure steam can be generated by using several individual tubes within the drum wall. The achievable heat transfer during the discharging process is exceeding 0.5 MW per meter of drum length at a drum diameter of 1 m. The storage system can be charged directly either by electric heaters or by using suitable heat pumps. CONCLUSION: With the rotating drum heat exchanger for latent heat storage, steam can be generated with constant power and high heat flux densities of above 200 kW/m2 based on the drums outer surface. The design can be realized on an industrial scale in the MW range

Activin and TGFβ use diverging mitogenic signaling in advanced colon cancer.

BackgroundUnderstanding cell signaling pathways that contribute to metastatic colon cancer is critical to risk stratification in the era of personalized therapeutics. Here, we dissect the unique involvement of mitogenic pathways in a TGFβ or activin-induced metastatic phenotype of colon cancer.MethodMitogenic signaling/growth factor receptor status and p21 localization were correlated in primary colon cancers and intestinal tumors from either AOM/DSS treated ACVR2A (activin receptor 2) -/- or wild type mice. Colon cancer cell lines (+/- SMAD4) were interrogated for ligand-induced PI3K and MEK/ERK pathway activation and downstream protein/phospho-isoform expression/association after knockdown and pharmacologic inhibition of pathway members. EMT was assessed using epithelial/mesenchymal markers and migration assays.ResultsIn primary colon cancers, loss of nuclear p21 correlated with upstream activation of activin/PI3K while nuclear p21 expression was associated with TGFβ/MEK/ERK pathway activation. Activin, but not TGFβ, led to PI3K activation via interaction of ACVR1B and p85 independent of SMAD4, resulting in p21 downregulation. In contrast, TGFβ increased p21 via MEK/ERK pathway through a SMAD4-dependent mechanism. While activin induced EMT via PI3K, TGFβ induced EMT via MEK/ERK activation. In vivo, loss of ACVR2A resulted in loss of pAkt, consistent with activin-dependent PI3K signaling.ConclusionAlthough activin and TGFβ share growth suppressive SMAD signaling in colon cancer, they diverge in their SMAD4-independent pro-migratory signaling utilizing distinct mitogenic signaling pathways that affect EMT. p21 localization in colon cancer may determine a dominant activin versus TGFβ ligand signaling phenotype warranting further validation as a therapeutic biomarker prior to targeting TGFβ family receptors

When Interactions Between Bile Salts and Cyclodextrin Cause a Negative Food Effect: Dynamic Dissolution/Permeation Studies with Itraconazole (Sporanox®) and Biomimetic Media

The marketed oral solution of itraconazole (Sporanox®) contains 40% (259.2&nbsp;mM) of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). The obvious role of HP-β-CD is to solubilize itraconazole and to overcome its poor aqueous solubility that restricts its absorption. In this study, we investigated the biorelevance of in vitro experiments by the influence of biomimetic media (containing bile salts and phospholipids) on the predicted itraconazole absorption from the commercial HP-β-CD-based Sporanox® solution. We performed phase-solubility studies of itraconazole and dynamic 2-step-dissolution/permeation studies using a biomimetic artificial barrier, Sporanox® solution, and fasted state simulated intestinal fluid (FaSSIF_V1). Both FaSSIF_V1 and HP-β-CD increased the apparent solubility of itraconazole when used individually. In combination, their solubility-enhancing effects were not additive probably due to the competition of bile salts with itraconazole for the hydrophobic cavity of HP-β-CD. Our combined dissolution/permeation experiments indicated the occurrence of a transient supersaturation from Sporanox® upon two-step dissolution. Through systematic variation of bile salt concentrations in the biomimetic media, it was observed that the extent and the duration of supersaturation depend on the concentrations of bile salts: supersaturation was rather stable in the absence of bile salts and phospholipids. The higher the bile salt concentration, the faster the collapse of the transient supersaturation occurred, an effect which is nicely mirrored by reduced in vitro permeation across the barrier. This is an indication of a negative food effect, which in fact correlates well with what earlier had been observed in clinical studies for Sporanox® solution. In essence, we could demonstrate that in vitro two-stage dissolution/permeation experiments using an artificial barrier and selected biomimetic media may predict the negative effects of the latter on cyclodextrin-based drug formulations like Sporanox® Oral Solution and, at the same time, provide a deeper mechanistic insight

The additional heat flux due to adhesion at a partially immersed rotating drum heat exchanger for latent heat storage

Latent heat storages can be used to store thermal energy at a constant temperature. By actively removing the solidified phase change material from the heat exchanger surface during the discharge process, the heat flux can be kept constant and a separation of power and capacity is possible. In the presented rotating drum concept, a cooled drum is partially immersed in a tub of liquid phase change material and rotates in it. Phase change material solidifies at the submerged part of the drum. In addition, adhering liquid phase change material solidifies after the surface has left the tub. In this paper, the additional heat transfer due to adhesion is examined by determining the solidified layer thickness as well as the heat transfer by comparing measurements with adhesion and while eliminating the adhesion with a rubber lip. The measured adhering layer thickness differs by 33% from a presented analytical approach. The transferred heat is increased up to 26 % due to the adhesion