New Vocabulary for Bacterial Communication

Quorum sensing (QS) is widely accepted as a procedure that bacteria use to converse. However, prevailing thinking places acyl homoserine lactones (AHLs) at the forefront of this communication pathway in Gram-negative bacteria. With the advent of high-throughput genomics and the subsequent influx of bacterial genomes, bioinformatics analysis has determined that the genes encoding AHL biosynthesis, originally discovered to be indispensable for QS (LuxI-like proteins and homologues), are often absent in QS-capable bacteria. Instead, the sensing protein (LuxR-like proteins) is present with an apparent inability to produce any outgoing AHL signal. Recently, several signals for these LuxR solos have been identified. Herein, advances in the field of QS are discussed, with a particular focus on recent research in the field of bacterial cell–cell communication.     

Molecular Effects of Auto-Antibodies on Angiotensin II Type 1 Receptor Signaling and Cell Proliferation

The angiotensin II (Ang II) type 1 receptor (AT₁R) is involved in the regulation of blood pressure (through vasoconstriction) and water and ion homeostasis (mediated by interaction with the endogenous agonist). AT₁R can also be activated by auto-antibodies (AT₁R-Abs), which are associated with manifold diseases, such as obliterative vasculopathy, preeclampsia and systemic sclerosis. Knowledge of the molecular mechanisms related to AT₁R-Abs binding and associated signaling cascade (dys-)regulation remains fragmentary. The goal of this study was, therefore, to investigate details of the effects of AT₁R-Abs on G-protein signaling and subsequent cell proliferation, as well as the putative contribution of the three extracellular receptor loops (ELs) to Abs-AT₁R signaling. AT₁R-Abs induced nuclear factor of activated T-cells (NFAT) signaling, which reflects G_q/11 and G_i activation. The impact on cell proliferation was tested in different cell systems, as well as activation-triggered receptor internalization. Blockwise alanine substitutions were designed to potentially investigate the role of ELs in AT₁R-Abs-mediated effects. First, we demonstrate that Ang II-mediated internalization of AT₁R is impeded by binding of AT₁R-Abs. Secondly, exclusive AT₁R-Abs-induced G_q/11 activation is most significant for NFAT stimulation and mediates cell proliferation. Interestingly, our studies also reveal that ligand-independent, baseline AT₁R activation of G_i signaling has, in turn, a negative effect on cell proliferation. Indeed, inhibition of G_i basal activity potentiates proliferation triggered by AT₁R-Abs. Finally, although AT₁R containing EL1 and EL3 blockwise alanine mutations were not expressed on the human embryonic kidney293T (HEK293T) cell surface, we at least confirmed that parts of EL2 are involved in interactions between AT₁R and Abs. This current study thus provides extended insights into the molecular action of AT₁R-Abs and associated mechanisms of interrelated pathogenesis.     

Harmonically Weighted Processes

We discuss a model for long memory and persistence in time series that amounts to harmonically weighting short memory processes, . A non-standard rate of convergence is required to establish a Gaussian functional central limit theorem. Theoretically, the harmonically weighted (HW) process displays less persistence and weaker memory than the classical competitor, fractional integration (FI) of order d. Still, we establish that a test rejects the null hypothesis of d = 0 if the process is HW. Similarly, a bias approximation shows that estimators of d will fail to distinguish between HW and FI given realistic sample sizes. The difficulties to disentangle HW and FI are illustrated experimentally and with USA inflation data.     

Optimizing conditional value-at-risk in dynamic pricing

OR Spectrum - Many industries use dynamic pricing on an operational level to maximize revenue from selling a fixed capacity over a finite horizon. Classical risk-neutral approaches do not...     

Bioavailability of iron sensed by a phytoplanktonic Fe-bioreporter

This study describes a short-term (12 h) evaluation of iron (Fe) bioavailability to an Fe-dependent cyanobacterial bioreporter derived from Synechococcus PCC 7942. Several synthetic ligands with variable conditional stability constants for Fe(lll) (K* of 10(19.8) to 10(30.9)), in addition to several defined natural Fe-binding ligands and a fulvic acid of aquatic origin (Suwannee River), were used to elucidate the forms of Fe that are discerned by this phytoplanktonic microbe: Fe-HEBD (log conditional stability constant, K*, = 28.1, HEBD = N,N'-di(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid monohydrochloride hydrate), Fe-HDFB (K* = 30.9, DFB = desferroxamine B), Fe-ferrichrome (K* = 23.2), Fe-DTPA (K* = 21.1, DTPA = diethylenetrinitrilopentaacetic acid), Fe-(8HQS)2 (K* = 20.4, 8HQS = 8-hydroxyquinoline-5-sulfonic acid), Fe-CDTA (K* = 19.8, CDTA = trans-1,2-cyclohexylenedinitrilotetraacetic acid), and Fe-EDTA (K* = 19.2). Iron bioavailability sensed by the bioreporter was related to diffusion limitation and activity of high-affinity transporters rather than by siderophore secretion. Iron complexed with a K* < 23.2 contributes to the bioavailable pool; bioavailability could be explained by disjunctive ligand exchange considerations and fully, partially, and nonbioavailable complexes could be distinguished according to their conditional stability constant. The use of Fe-bioreporters provides a relevant measurement of bioavailability to an important group of primary producers in freshwaters (cyanobacteria) and is thus a promising technique for understanding Fe cycling in aquatic systems.     

New Radioligands for Describing the Molecular Pharmacology of MT1 and MT2 Melatonin Receptors

Melatonin receptors have been studied for several decades. The low expression of the receptors in tissues led the scientific community to find a substitute for the natural hormone melatonin, the agonist 2-[¹²⁵I]-iodomelatonin. Using the agonist, several hundreds of studies were conducted, including the discovery of agonists and antagonists for the receptors and minute details about their molecular behavior. Recently, we attempted to expand the panel of radioligands available for studying the melatonin receptors by using the newly discovered compounds SD6, DIV880, and {"type":"entrez-nucleotide","attrs":{"text":"S70254","term_id":"546525","term_text":"S70254"}}S70254. These compounds were characterized for their affinities to the hMT₁ and hMT₂ recombinant receptors and their functionality in the classical GTPγS system. SD6 is a full agonist, equilibrated between the receptor isoforms, whereas {"type":"entrez-nucleotide","attrs":{"text":"S70254","term_id":"546525","term_text":"S70254"}}S70254 and DIV880 are only partial MT₂ agonists, with K_i in the low nanomolar range while they have no affinity to MT₁ receptors. These new tools will hopefully allow for additions to the current body of information on the native localization of the receptor isoforms in tissues.     

Sell or store? An ADP approach to marketing renewable energy

In deregulated markets, electricity is usually traded in advance, and the advance commitments have a time lag of several periods. For example, in the German intraday market, the seller commits to providing electricity 45 min before the 15-min interval in which delivery has to be made. We consider the problem of a producer that generates energy from stochastic, renewable sources, such as solar or wind and uses a storage device with conversion losses. We model the problem as a Markov Decision Process and consider lagged commitments for the first time in the literature. The problem is solved using an innovative approximate dynamic programming approach. Its key elements are the analytical derivation of the optimal action based on the value function approximation and a new combination of approximate policy iteration with classical backward induction. The new approach is quite general with regard to the stochastic processes describing the energy production and price evolution. We demonstrate the application of our approach by considering a wind farm/storage combination. A numerical study using real-world data shows the applicability and performance of the new approach and investigates how the storage device’s parameters influence profit.     

Mortality analysis of an urban building stock

Research is presented on the estimation of the lifespan of cohorts of buildings and building stocks. This is based on the analysis of extensive longitudinal data of the 55?000 buildings in the City of Zurich from 1832 and 2010. The survival probability from different perspectives considers age, construction periods, and demolition periods for both existing and demolished buildings. Survival probability is established using a Kaplan–Meier estimator. A more in-depth approach to the mortality of buildings is then determined by differentiating building age, use, size and geographical situation (district). The use of a common geographical information system (GIS) allows longitudinal building data to be linked to a geographical hierarchy of three levels of analysis (city, district and building) accounting for the different granularity on each level (neighbourhoods, quarters, building parts). A comparison of the two methods indicates that the choice of the observed time periods can lead to very different results. The analysis of the three levels shows the possibilities and limits of combined statistical and historical approaches. Mortality analysis is a promising approach to inform policy and practice; it could become a new link between long-term scenario planning, construction policies and institutional regimes.     

Creating a reference database of cargo inspection X-ray images using high energy radiographs of cargo mock-ups

Customs continue to use a wide range of technology in protecting against terrorism and the movement of illicit trade and prohibited imports. The throughput of scanned vehicles and cargo increases and just keeps on growing. Therefore, the need of automated algorithms to help screening officers in inspection, examination or surveillance of vehicles and containers is crucial. In this context, the successful collaboration between manufacturers and customs offices is of key importance. Facing this topic, within the seventh framework program of the European Commission, the project ACXIS “Automated Comparison of X-ray Images for cargo Scanning” arose. The main objective of this project is to develop a manufacturer independent reference database for X-ray images of illicit and licit cargo. Historic images of real detections, images of illegal cargo mock-ups as well as images of legitimate cargo will be integrated into the reference database. For this, procedures and algorithms to uniform X-ray images of different cargo scanners was developed, as well as an automated identification method of potentially illicit cargo. Finally, these developments were incorporated in creating a training simulator and a toolbox for inspection officers enhanced X-ray screening competence.