Hydrogel microwell arrays allow the assessment of protease-associated enhancement of cancer cell aggregation and survival

Current routine cell culture techniques are only poorly suited to capture the physiological complexity of tumor microenvironments, wherein tumor cell function is affected by intricate three-dimensional (3D), integrin-dependent cell-cell and cell-extracellular matrix (ECM) interactions. 3D cell cultures allow the investigation of cancer-associated proteases like kallikreins as they degrade ECM proteins and alter integrin signaling, promoting malignant cell behaviors. Here, we employed a hydrogel microwell array platform to probe using a high-throughput mode how ovarian cancer cell aggregates of defined size form and survive in response to the expression of kallikreins and treatment with paclitaxel, by performing microscopic, quantitative image, gene and protein analyses dependent on the varying microwell and aggregate sizes. Paclitaxel treatment increased aggregate formation and survival of kallikrein-expressing cancer cells and levels of integrins and integrin-related factors. Cancer cell aggregate formation was improved with increasing aggregate size, thereby reducing cell death and enhancing integrin expression upon paclitaxel treatment. Therefore, hydrogel microwell arrays are a powerful tool to screen the viability of cancer cell aggregates upon modulation of protease expression, integrin engagement and anti-cancer treatment providing a micro-scaled yet high-throughput technique to assess malignant progression and drug-resistance.

Outdoor flight testing of a pole inspection UAV incorporating high-speed vision

We present a pole inspection system for outdoor environments comprising a high-speed camera on a vertical take-off and landing (VTOL) aerial platform. The pole inspection task requires a vehicle to fly close to a structure while maintaining a fixed stand-off distance from it. Typical GPS errors make GPS-based navigation unsuitable for this task however. When flying outdoors a vehicle is also affected by aerodynamics disturbances such as wind gusts, so the onboard controller must be robust to these disturbances in order to maintain the stand-off distance. Two problems must therefor be addressed: fast and accurate state estimation without GPS, and the design of a robust controller. We resolve these problems by a) performing visual + inertial relative state estimation and b) using a robust line tracker and a nested controller design. Our state estimation exploits high-speed camera images (100Hz) and 70Hz IMU data fused in an Extended Kalman Filter (EKF). We demonstrate results from outdoor experiments for pole-relative hovering, and pole circumnavigation where the operator provides only yaw commands. Lastly, we show results for image-based 3D reconstruction and texture mapping of a pole to demonstrate the usefulness for inspection tasks.

Is intent-aware expected reciprocal rank sufficient to evaluate diversity?

In this paper we define two models of users that require diversity in search results; these models are theoretically grounded in the notion of intrinsic and extrinsic diversity. We then examine Intent-Aware Expected Reciprocal Rank (ERR-IA), one of the official measures used to assess diversity in TREC 2011-12, with respect to the proposed user models. By analyzing ranking preferences as expressed by the user models and those estimated by ERR-IA, we investigate whether ERR-IA assesses document rankings according to the requirements of the diversity retrieval task expressed by the two models. Empirical results demonstrate that ERR-IA neglects query-intents coverage by attributing excessive importance to redundant relevant documents. ERR-IA behavior is contrary to the user models that require measures to first assess diversity through the coverage of intents, and then assess the redundancy of relevant intents. Furthermore, diversity should be considered separately from document relevance and the documents positions in the ranking.

Tethering for Selective Synthesis of 2,2′-Biphenols : the Acetal Method

2,2'-Biphenols are a large and diverse group of compounds with exceptional properties both as ligands and bioactive agents. Traditional methods for their synthesis by oxidative dimerisation are often problematic and lead to mixtures of ortho- and para-connected regioisomers. To compound these issues, an intermolecular dimerisation strategy is often inappropriate for the synthesis of heterodimers. The ‘acetal method’ provides a solution for these problems: stepwise tethering of two monomeric phenols enables heterodimer synthesis, enforces ortho regioselectivity and allows relatively facile and selective intramolecular reactions to take place. The resulting dibenzo[1,3]dioxepines have been analysed by quantum chemical calculations to obtain information about the activation barrier for ring flip between the enantiomers. Hydrolytic removal of the dioxepine acetal unit revealed the 2,2′-biphenol target.

Social Media Analytics : Ein interdisziplinärer Ansatz und seine Implikationen für die Wirtschaftsinformatik [Social Media Analytics - An Interdisciplinary Approach and Its Implications for Information Systems]

Social Media Analytics ist ein neuer Forschungsbereich, in dem interdisziplinäre Methoden kombiniert, erweitert und angepasst werden, um Social-Media-Daten auszuwerten. Neben der Beantwortung von Forschungsfragen ist es ebenfalls ein Ziel, Architekturentwürfe für die Entwicklung neuer Informationssysteme und Anwendungen bereitzustellen, die auf sozialen Medien basieren. Der Beitrag stellt die wichtigsten Aspekte des Bereichs Social Media Analytics vor und verweist auf die Notwendigkeit einer fächerübergreifenden Forschungsagenda, für deren Erstellung und Bearbeitung der Wirtschaftsinformatik eine wichtige Rolle zukommt.

Social media analytics: an interdisciplinary approach and its implications for information systems

Social Media Analytics is an emerging interdisciplinary research field that aims on combining, extending, and adapting methods for analysis of social media data. On the one hand it can support IS and other research disciplines to answer their research questions and on the other hand it helps to provide architectural designs as well as solution frameworks for new social media-based applications and information systems. The authors suggest that IS should contribute to this field and help to develop and process an interdisciplinary research agenda.

Xanthones from fungi, lichens, and bacteria : the natural products and their synthesis

Many fungi, lichens, and bacteria produce xanthones (derivatives of 9H-xanthen-9-one, “xanthone” from the Greek “xanthos”, for “yellow”) as secondary metabolites. Xanthones are typically polysubstituted and occur as either fully aromatized, dihydro-, tetrahydro-, or, more rarely, hexahydro-derivatives. This family of compounds appeals to medicinal chemists because of their pronounced biological activity within a notably broad spectrum of disease states, a result of their interaction with a correspondingly diverse range of target biomolecules. This has led to the description of xanthones as “privileged structures”.(1) Historically, the total synthesis of the natural products has mostly been limited to fully aromatized targets. Syntheses of the more challenging partially saturated xanthones have less frequently been reported, although the development in recent times of novel and reliable methods for the construction of the (polysubstituted) unsaturated xanthone core holds promise for future endeavors. In particular, the fascinating structural and biological properties of xanthone dimers and heterodimers may excite the synthetic or natural product chemist.

Rediscovering the double Friedel-Crafts acylation : an expedient entry to phenanthrene-9,10-diones

The double Friedel–Crafts acylation of readily accessible biaryls with oxalyl chloride delivers the respective phenanthrene-9,10-diones, providing an alternative to the traditional methods, which require harsh oxidizing conditions and multistep sequences. This simple method allows the synthesis of various symmetrical and non-symmetrical targets, and is even effective for the synthesis of the parent ring system from (unactivated) biphenyl.

The acetal concept : regioselective access toortho,ortho-diphenols via dibenzo-1,3-dioxepines

Traditional methods are ill-suited for the synthesis of ortho,ortho-biphenols, a structural motif found in many polyphenolic natural products, as well as synthetically useful compounds such as the chiral ligands binol, vapol, and vanol. The new route consists of a radical-based reaction of an acetal-tethered biphenyl ether substrate and subsequent hydrolytic cleavage of the dibenzo-1,3-dioxepine intermediate.

ortho-Bromo(propa-1,2-dien-1-yl)arenes : substrates for domino reactions

o-Bromo(propa-1,2-dien-1-yl)arenes exhibit novel and orthogonal reactivity under Pd catalysis in the presence of secondary amines to form enamines (concerted Pd insertion, intramolecular carbopalladation, and terminative Buchwald–Hartwig coupling) and of amides to form indoles (addition, Buchwald–Hartwig cyclization, and loss of the acetyl group). The substrates for these reactions can be accessed in a reliable and highly selective two-step process from 2-bromoaryl bromides.

Synthesis of novel inhibitors blocking Wnt signaling downstream of β-Catenin

Large scale screening of libraries consisting of natural and small molecules led to the identification of many small molecule inhibitors repressing Wnt/β-Catenin signaling. However, targeted synthesis of novel Wnt pathway inhibitors has been rarely described. We developed a modular and expedient way to create the aromatic ring system with an aliphatic ring in between. Our synthesis opens up the possibility, in principle, to substitute all positions at the ring system with any desired substituent. Here, we tested five different haloquinone analogs carrying methoxy- and hydroxy-groups at different positions. Bona fide Wnt activity assays in cell culture and in Xenopus embryos revealed that two of these compounds act as potent inhibitors of aberrant activated Wnt/β-Catenin signaling.

Double trouble — the art of synthesis of chiral dimeric natural products

Double or nothing! Recently the total ynthesis of secalonic acids A and D was reported. This work and other natural product syntheses with a dimerization step as a common feature are featured in this highlight. The significant biological activity of the secalonic acids and the fact that their synthesis has fascinated synthetic chemists for the past forty years make this work a milestone in natural product synthesis.

Solid-state structure of some substituted hexahydro-1,4:5,8-diepoxy­naphthalenes

The structure of several carboxy-substituted hexahydro-1,4:5,8-diepoxynaphthalenes have been solved with X-ray crystallography, in some cases confirming previously contentious structures. The compounds of interest are constructed in efficient one-step 2 × [4+2] cycloaddition reactions from furan and acetylene carboxylate derivatives.

The Chemistry of Mycotoxins

Mycotoxins – from the Greek μύκης (mykes, mukos) “fungus” and the Latin (toxicum) “poison” – are a large and growing family of secondary metabolites and hence natural products produced by fungi, in particular by molds (1). It is estimated that well over 1,000 mycotoxins have been isolated and characterized so far, but this number will increase over the next few decades due the availability of more specialized analytical tools and the increasing number of fungi being isolated. However, the most important classes of fungi responsible for these compounds are Alternaria, Aspergillus (multiple forms), Penicillium, and Stachybotrys. The biological activity of mycotoxins ranges from weak and/or sometimes positive effects such as antibacterial activity (e.g. penicillin derivatives derived from Penicillium strains) to strong mutagenic (e.g. aflatoxins, patulin), carcinogenic (e.g. aflatoxins), teratogenic, neurotoxic (e.g. ochratoxins), nephrotoxic (e.g. fumonisins, citrinin), hepatotoxic, and immunotoxic (e.g. ochratoxins, diketopiperazines) activities (1, 2), which are discussed in detail in this volume.