Complex-network analysis of combinatorial spaces: The NK landscape case

We propose a network characterization of combinatorial fitness landscapes by adapting the notion of inherent networks proposed for energy surfaces. We use the well-known family of NK landscapes as an example. In our case the inherent network is the graph whose vertices represent the local maxima in the landscape, and the edges account for the transition probabilities between their corresponding basins of attraction. We exhaustively extracted such networks on representative NK landscape instances, and performed a statistical characterization of their properties. We found that most of these network properties are related to the search difficulty on the underlying NK landscapes with varying values of K.Comment: arXiv admin note: substantial text overlap with arXiv:0810.3492, arXiv:0810.348

Optimierung der Isolierung von Oleocanthal

Der Konsum an Olivenöl in mediterranen Ländern gilt als bedeutsamer Beitrag für das deutlich geringere Auftreten von chronisch-degenerativen Erkrankungen des kardiovaskulären Systems in der Bevölkerung Griechenlands oder Italiens im Vergleich zu Nord- oder Mitteleuropa, das mit einer höheren Lebenserwartung verbunden ist. Olivenöl enthält neben ungesättigten Fettsäuren auch phenolische Secoiridoide, wie z.B. Oleuropein oder Ligstrosid, welche antiinflammatorische, antimikrobielle und antioxidative Wirkung besitzen. Oleocanthal (OLC) ist ein besonders aktives offenkettiges Derivat dieser Phenole, das aufgrund seines Ibuprofen-ähnlichen kratzenden Geschmacks wissenschaftliches Interesse erlangt hat. Da OLC kommerziell nicht erhältlich ist und synthetisch nur über eine aufwendige mehrstufige Synthese zugänglich ist, war es für geplante pharmakologische Versuche notwendig, Oleocanthal aus Olivenöl zu isolieren. In vorangegangenen Arbeiten wurde Oleocanthal aus einem methanolischen Extrakt mittels HPLC angereichert und in Form von zwei cis/trans-Isomeren erhalten. Das Ziel dieser Diplomarbeit war, zu ermitteln, ob die HPCCC für die Auftrennung einer Olivenölphenolfraktion (OPF) und somit zur Isolierung von OLC geeignet ist. Für die Auftrennung wurde ein Multi layer coil-System (Dynamic Extractions, UK) verwendet. Bei einer Injektionsmenge von 100 mg OPF konnte OLC mit Hilfe des Fließmittelsystems (FMS) Hexan-EtOAc-MeOH-H2O (5+6+5+6) auf der analytischen Säule (Volumen 32 ml) in einer Reinheit von bis zu 31% in den Sammelfraktionen angereichert werden. Diese Anreicherung wurde im Scale-up (Auftrennung von 200 bzw. 400 mg OLC in der analytischen Säule) nicht erreicht, woraus sich schließen lässt, dass die analytische Säule nicht mit zu hohen Extraktmengen beschickt werden sollte. Auf der präparativen Säule (Volumen 140 ml) wurden 1000 mg OPF aufgetrennt. Das chromatografische Muster der aufgetrennten Fraktionen war jenem des analytischen Laufs sehr ähnlich, was auf eine ähnlich gute Trennleistung schließen ließ. Unter diesen Bedingungen wurde ein Anteil von maximal 28% OLC in den Sammelfraktionen erreicht. Im Umkehrphasenmodus wurde OLC zu schnell eluiert und keine bessere Auftrennung erreicht. In allen Experimenten wurde – wie in der HPLC-Trennung – ein Gemisch von zwei cis/trans-Isomeren erhalten. Daraus kann geschlossen werden, dass es in Lösungen von OLC immer zur Bildung dieser Isomeren kommt. Das FMS Hexan-MeOH-H2O (10+9+1), das im Rahmen weiterer Versuche eingesetzt wurde und für die Auftrennung von polaren Fettsäuren beschrieben worden war, führte weder im Normal- noch im Umkehrphasenmodus zu erfolgreichen Auftrennungen. OLC konnte im Zuge dieser Diplomarbeit mittels HPCCC unter Verwendung des FMS Hexan-EtOAc-MeOH-H2O (5+6+5+6) in einem Arbeitsschritt in bis zu 31%iger Reinheit angereichert werden. Die Methode ist der analytischen bzw. semipräparativen HPLC deutlich überlegen, da größere Extraktmengen rasch getrennt werden können und Oxidationsprodukte besser abgetrennt bzw. ihre Bildung vermieden werden.The consumption of olive oil in Mediterranean countries is a significant factor for the less frequent occurence of cardiovascular diseases in the population of Greece or Italy in comparison to Northern or Central European countries which leads to a higher life expectancy. Besides unsaturated fatty acids olive oil contains phenolic secoiridoids, such as oleuropein or ligstrosid which show anti-inflammatory, anti-microbial and anti-oxidative activities. Oleocanthal (OLC) is a very potent derivative of these phenolics and came into the focus of interest due to its throat-irritating effect similar to the one known from the NSAID ibuprofen. As OLC is commercially not available and can only be provided by complex chemical synthesis the elaboration of a convenient method for the isolation of OLC from olive oil to investigate its pharmacological properties, was the aim of this thesis. In an earlier study OLC was obtained from a methanolic extract by HPLC and was enriched in the form of two cis/trans isomers. This thesis investigated the potential of HPCCC for the separation of an olive oil phenol fraction (OPF) and the isolation of OLC. For this purpose a multi layer coil-system (Dynamic Extractions, UK) was used. In the separation of 100 mg OPF under use of the solvent system hexane-EtOAc-MeOH-H2O (5+6+5+6) in the analytical coil (volume 32 ml) OLC was enriched up to about 31%. In scale-up (separation of 200 und 400mg in the analytical coil) a similar separation but lower enrichment was achieved. This result showed that the loading to the analytical column should be kept in a lower range. For the separation in the preparative coil (volume 140 ml) 1000 mg OPF were injected. The similar chromatographic fingerprint in comparison to the one after separation in the analytical coil shows a comparable quality of separation. OLC was enriched up to about 28%. In the reversed phase mode OLC was eluted very fast, and no separation was achieved. The solvent system hexane-MeOH-H2O (10+9+1), which had been used for the separation of polar fatty acids, did not lead to a successful separation, neither in the normal phase nor in the reversed phase mode. This study showed that OLC can be enriched from a methanolic extract of olive oil to a purity of about 31% in one single HPCCC run using the solvent system hexane-EtOAc-MeOH-H2O (5+6+5+6). The fractionation by HPCCC is superior to analytical and semipreparative HPLC as higher amounts of OPF can be separated in short time and oxidation/degradation products are removed more efficiently

AMon: A domain-specific language and framework for adaptive monitoring of Cyber–Physical Systems

Cyber–Physical Systems (CPS) are increasingly used in safety–critical scenarios where ensuring their correct behavior at runtime becomes a crucial task. Therefore, the behavior of the CPS needs to be monitored at runtime so that violations of requirements can be detected. With the inception of edge devices that facilitate runtime analysis at the edge and the increasingly diverse environments that CPS operate in, flexible monitoring approaches are needed that consider the data that needs to be monitored and the analyses performed on that data. In this paper, we propose AMon, a flexible adaptive monitoring framework that supports the specification and validation of monitoring adaptation rules, using a domain-specific language. Based on these rules, AMon automatically generates code for direct deployment onto devices. We evaluated AMon by applying it to TurtleBot Robots and a fleet of Unmanned Aerial Vehicles. Furthermore, we conducted a user study assessing the understandability and ease of use of our language. Results show that creating multiple adaptation rules with our DSL is feasible with minimal effort, and that adaptive monitoring can reduce the amount of runtime data transmitted from the edge device according to the current state of the system and its monitoring needs

SMB Operation for Three-Fraction Separations: Purification of Plasmid DNA

The Simulated Moving Bed technology is extended to incorporate a cleaning in place step, and it is then applied by exploiting size exclusion chromatography to purify plasmid DNA. Experimental performances are discussed in the light of our theoretical understanding of the SMB behavio

Growth in a Circular Economy

We present a model of natural resources and growth that stresses the influence of an incomplete circularity of exhaustible natural resources. In particular, we analyze the recycling process and the material balance principle, two fundamental aspects of a circular economy. When market failures arise or complete recycling is not possible for technical reasons, then the equilibrium outcomes in terms of output, consumption, and prices for the material inputs are distorted compared to the socially optimal solution. However, the introduction of a market for waste and a system of subsidies/taxes on virgin and recycled resources enables an internalization of the externalities. The importance of technological progress in order to foster “circularity”, i.e. both to improve resource efficiency in the production process and to enhance the backflow of materials from waste to production, is highlighted

Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR Studies

[EN] The first semisynthesis and biological profiling of the new abietane diterpenoid (+)-liquiditerpenoic acid A (abietopinoic acid) (7) along with several analogues are reported. The compounds were obtained from readily available methyl dehydroabietate (8), which was derived from (-)-abietic acid (1). Biological comparison was conducted according to the different functional groups, leading to some basic structure-activity relationships (SAR). In particular, the ferruginol and sugiol analogues 7 and 10-16 were characterized by the presence of an acetylated phenolic moiety, an oxidized C-7 as a carbonyl, and a different functional group at C-18 (methoxycarbonyl, carboxylic acid, and hydroxymethyl). The biological properties of these compounds were investigated against a panel of six representative human tumor solid cells (A549, HBL-100, HeLa, SWI573, T-47D, and WiDr), five leukemia cellular models (NALM-06, KOPN-8, SUP-B15, UoCB1, and BCR-ABL), and four Leishmania species (L. infantum, L. donovani, L. amazonensis, and L. guyanensis). A molecular docking study pointed out some targets in these Leishmania species. In addition, the ability of the compounds to modulate GABA(A) receptors (alpha(1)beta(2)gamma(2s)) is also reported. The combined findings indicate that these abietane diterpenoids offer a source of novel bioactive molecules with promising pharmacological properties from cheap chiral-pool building blocks.Financial support by the Spanish Government [Consejo Superior de Investigaciones Cientificas (2016801008)] is gratefully acknowledged. M.S. thanks the support by the doctoral program "Molecular Drug Targets" (Austrian Science Fund FWF W 1232). F.R thanks the American Lebanese Syrian Associated Charities (ALSAC). M.A.D.-A. thanks the Santander Bank for the support for her project in consolidable groups of CEU-UCH.Hamulic, D.; Stadler, M.; Hering, S.; Padron, JM.; Bassett, R.; Rivas, F.; Loza-Mejia, M.... (2019). Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR Studies. Journal of Natural Products. 82(4):823-831. https://doi.org/10.1021/acs.jnatprod.8b00884S82383182

Nachhaltigkeitsanforderungen und -bewertung in Living Labs: Konzeption eines Bewertungsmodells : Arbeitspapier im Arbeitspaket 2 (AS 2.1) im INNOLAB Projekt "Living Labs in der Green Economy: realweltliche Innovationsräume für Nutzerintegration und Nachhaltigkeit"

Das Thema dieses Papieres ist die Integration von Nachhaltigkeitskriterien in den Innovationsprozess von Living Labs. Es wurde ein Bewertungsmodell entwickelt, welches den Innovationsprozess in Living Labs zu strukturieren hilft, indem die Anforderungen und Bewertungskriterien definiert werden, die den Innovationsprozess unter dem Nachhaltigkeitsvorzeichen leiten können. Das Modell "Bewertung von Nachhaltigkeitswirkungen im Living Lab Innovationsprozess" stellt den Innovationsprozesses in Living Labs dar und hilft dabei, konzeptionell Nachhaltigkeitskriterien auf Grundlage verschiedener Anforderungsgruppen abzuleiten. Dieses Papier ist ein Ergebnis aus dem Arbeitspaket 2 "Operationalisierung" im Rahmen des Projektes "Living Labs in der Green Economy: Realweltliche Innovationsräume für Nutzerintegration und Nachhaltigkeit" (INNOLAB), das im Rahmen der Sozial-ökologischen Forschung zum Themenschwerpunkt "Nachhaltiges Wirtschaften" vom Bundesforschungsministerium gefördert wird

Translation elongation can control translation initiation on eukaryotic mRNAs

Synonymous codons encode the same amino acid, but differ in other biophysical properties. The evolutionary selection of codons whose properties are optimal for a cell generates the phenomenon of codon bias. Although recent studies have shown strong effects of codon usage changes on protein expression levels and cellular physiology, no translational control mechanism is known that links codon usage to protein expression levels. Here, we demonstrate a novel translational control mechanism that responds to the speed of ribosome movement immediately after the start codon. High initiation rates are only possible if start codons are liberated sufficiently fast, thus accounting for the observation that fast codons are overrepresented in highly expressed proteins. In contrast, slow codons lead to slow liberation of the start codon by initiating ribosomes, thereby interfering with efficient translation initiation. Codon usage thus evolved as a means to optimise translation on individual mRNAs, as well as global optimisation of ribosome availability

Theory of double Cooper-pair tunneling and light emission mediated by a resonator

Photon emission by tunneling electrons can be encouraged by locating a resonator close to the tunnel junction and applying an appropriate voltage-bias. However, studies of normal metals show that the resonator also affects how the charges flow, facilitating processes in which correlated tunneling of two charges produces one photon. We develop a theory to analyze this kind of behavior in Josephson junctions by deriving an effective Hamiltonian describing processes where two Cooper-pairs generate a single photon. We determine the conditions under which the transport is dominated by incoherent tunneling of two Cooper-pairs, whilst also uncovering a regime of coherent double Cooper-pair tunneling. We show that the system can also display an unusual form of photon-blockade and hence could serve as a single-photon source