Computing the update of the repeated median regression line in linear time

The repeated median line estimator is a highly robust method for fitting a regression line to a set of n data points in the plane. In this paper, we consider the problem of updating the estimate after a point is removed from or added to the data set. This problem occurs, e.g., in statistical online monitoring, where the computational effort is often critical. We present a deterministic algorithm for the update working in O(n) time and O(n²) space.     

A Tractable Class of Maximal Hedging Policies in Multi-Part Manufacturing Systems

The flow control problem in multi-part failure prone manufacturing systems is considered. While computationnaly attractive, the near optimal controllers of Caramanis and Sharifnia, suffer from the drawback that the production capacity set must be approximated via a very restricted set of inscribed hypercubes, namely those for which a componentwise feasibility requirement is satisfied. Also, due to the completely decoupled nature of production along each component, utilization of the restricted capacity set is suboptimal. A class of capacity set incribed hypercube policies called simple maximal hedging (SMH) policies is introduced. In SMH policies production levels along the various components of the capacity set are coupled, the componentwise feasibility requirement is lifted, and there is no underutilization of production capacity if needed. In a p part types manufacturing system, for partwise additive cost functionals, it is shown that performance evaluation of a given SMH policy reduces to the analysis of p decoupled (fictitious) semi-Markovian machines. The machines are Markovianized via first passage-time analysis and a Padé approximants technique. Numerical optimization over the class of SMH policies in a sample manufacturing system indicates that their performance can come close to that of the optimal control.     

Microscopy under pressure--an optical chamber system for fluorescence microscopic analysis of living cells under high hydrostatic pressure

High hydrostatic pressure (HHP) becomes more and more interesting for life science research, since it can be employed to inactivate various cells. To directly monitor "cells under pressure," the development of an optical high-pressure chamber is required. Therefore, an optical pressure chamber that can be used for up to 300 MPa was constructed. This chamber has already been described as a tool for in situ observation of dynamic changes of microscopic structures in bright field as well as phase contrast. In combination with an inverted microscope, we obtained brilliant microscopic color pictures with an optical resolution more than 0.56 microm. Here, we demonstrate the capabilities of the HHP cell, in combination with epifluorescence microscopy. Using a nonadherent human B-cell line (Raji, ATCC CCL 86), stained with the fluorescent dyes propidium iodide, Hoechst 33342, or dihexyloxacarbocyanine iodide, we were able to show that the system is suitable to perform fluorescence microscopic analyses, with pressures up to 300 MPa, with viable mammalian cells.     

Information Theory and Neural Networks for Managing Uncertainty in Flood Routing

This paper presents an approach for handling uncertainties arising mainly from ignored or misrepresented processes in physically based models. The approach is based on the application of a parallel artificial neural network (ANN) model that uses state variables, input and output data, and previous model errors at specific time steps to predict the errors of a physically based model. Concepts from information theory are used to discover the relationships between the variables and the model errors, which also serves as a mechanism to detect the predictability of the errors. The resulting information is used to select the best related input data for the error prediction model. The error prediction model is then trained and applied to improve the forecasts made by the physically based model. This approach was applied to a routing model of a 70 km reach of the River Wye, United Kingdom. The results demonstrate that errors from the physically based model show a consistent trend governed by some dynamics of their own, which can be modeled with learning algorithms. Errors were forecasted at different lead times. In all cases the forecasts made by the combined application of both models were more accurate than those made by the physically based model alone. From this it was concluded that, along with proper information analysis techniques, the use of ANN models to predict the forecast errors of physically based models can help to improve significantly the prediction and therefore to reduce the associated uncertainty.     

Binding Properties of RNA Quadruplex of SARS-CoV-2 to Berberine Compared to Telomeric DNA Quadruplex

Previous studies suggest that berberine, an isoquinoline alkaloid, has antiviral potential and is a possible therapeutic candidate against SARS-CoV-2. The molecular underpinnings of its action are still unknown. Potential targets include quadruplexes (G4Q) in the viral genome as they play a key role in modulating the biological activity of viruses. While several DNA-G4Q structures and their binding properties have been elucidated, RNA-G4Qs such as RG-1 of the N-gene of SARS-CoV-2 are less explored. Using biophysical techniques, the berberine binding thermodynamics and the associated conformational and hydration changes of RG-1 could be characterized and compared with human telomeric DNA-G4Q 22AG. Berberine can interact with both quadruplexes. Substantial changes were observed in the interaction of berberine with 22AG and RG-1, which adopt different topologies that can also change upon ligand binding. The strength of interaction and the thermodynamic signatures were found to dependent not only on the initial conformation of the quadruplex, but also on the type of salt present in solution. Since berberine has shown promise as a G-quadruplex stabilizer that can modulate viral gene expression, this study may also contribute to the development of optimized ligands that can discriminate between binding to DNA and RNA G-quadruplexes.     

Characterization of the Basal and mTOR-Dependent Acute Pulmonary and Systemic Immune Response in a Murine Model of Combined Burn and Inhalation Injury

Severe burn injury leads to a cascade of local and systemic immune responses that trigger an extreme state of immune dysfunction, leaving the patient highly susceptible to acute and chronic infection. When combined with inhalation injury, burn patients have higher mortality and a greater chance of developing secondary respiratory complications including infection. No animal model of combined burn and inhalation injury (B+I) exists that accurately mirrors the human clinical picture, nor are there any effective immunotherapies or predictive models of the risk of immune dysfunction. Our earlier work showed that the mechanistic/mammalian target of rapamycin (mTOR) pathway is activated early after burn injury, and its chemical blockade at injury reduced subsequent chronic bacterial susceptibility. It is unclear if mTOR plays a role in the exacerbated immune dysfunction seen after B+I injury. We aimed to: (1) characterize a novel murine model of B+I injury, and (2) investigate the role of mTOR in the immune response after B+I injury. Pulmonary and systemic immune responses to B+I were characterized in the absence or presence of mTOR inhibition at the time of injury. Data describe a murine model of B+I with inhalation-specific immune phenotypes and implicate mTOR in the acute immune dysfunction observed.     

Automatic image annotation using visual content and folksonomies

Automatic image annotation is an important and challenging task, and becomes increasingly necessary when managing large image collections. This paper describes techniques for automatic image annotation that take advantage of collaboratively annotated image databases, so called visual folksonomies. Our approach applies two techniques based on image analysis: First, classification annotates images with a controlled vocabulary and second tag propagation along visually similar images. The latter propagates user generated, folksonomic annotations and is therefore capable of dealing with an unlimited vocabulary. Experiments with a pool of Flickr images demonstrate the high accuracy and efficiency of the proposed methods in the task of automatic image annotation. Both techniques were applied in the prototypical tag recommender “tagr”.     

Zur Kenntnis des thermoplastischen Verhaltens von Holz

Ohne Zusammenfassung Mitteilung aus der Bundesanstalt für Forst- und Holzwirtschaft, Reinbek bei Hamburg.     

Sphk1 and Sphk2 Differentially Regulate Erythropoietin Synthesis in Mouse Renal Interstitial Fibroblast-like Cells

Erythropoietin (Epo) is a crucial hormone regulating red blood cell number and consequently the hematocrit. Epo is mainly produced in the kidney by interstitial fibroblast-like cells. Previously, we have shown that in cultures of the immortalized mouse renal fibroblast-like cell line FAIK F3-5, sphingosine 1-phosphate (S1P), by activating S1P₁ and S1P₃ receptors, can stabilize hypoxia-inducible factor (HIF)-2α and upregulate Epo mRNA and protein synthesis. In this study, we have addressed the role of intracellular iS1P derived from sphingosine kinases (Sphk) 1 and 2 on Epo synthesis in F3-5 cells and in mouse primary cultures of renal fibroblasts. We show that stable knockdown of Sphk2 in F3-5 cells increases HIF-2α protein and Epo mRNA and protein levels, while Sphk1 knockdown leads to a reduction of hypoxia-stimulated HIF-2α and Epo protein. A similar effect was obtained using primary cultures of renal fibroblasts isolated from wildtype mice, Sphk1−/−, or Sphk2−/− mice. Furthermore, selective Sphk2 inhibitors mimicked the effect of genetic Sphk2 depletion and also upregulated HIF-2α and Epo protein levels. The combined blockade of Sphk1 and Sphk2, using Sphk2−/− renal fibroblasts treated with the Sphk1 inhibitor PF543, resulted in reduced HIF-2α and Epo compared to the untreated Sphk2−/− cells. Exogenous sphingosine (Sph) enhanced HIF-2α and Epo, and this was abolished by the combined treatment with the selective S1P₁ and S1P₃ antagonists NIBR-0213 and TY52156, suggesting that Sph was taken up by cells and converted to iS1P and exported to then act in an autocrine manner through S1P₁ and S1P₃. The upregulation of HIF-2α and Epo synthesis by Sphk2 knockdown was confirmed in the human hepatoma cell line Hep3B, which is well-established to upregulate Epo production under hypoxia. In summary, these data show that sphingolipids have diverse effects on Epo synthesis. While accumulation of intracellular Sph reduces Epo synthesis, iS1P will be exported to act through S1P₁₊₃ to enhance Epo synthesis. Furthermore, these data suggest that selective inhibition of Sphk2 is an attractive new option to enhance Epo synthesis and thereby to reduce anemia development in chronic kidney disease.