On-line reverse isotope dilution analysis for spatial quantification of elemental labels used in immunohistochemical assisted imaging mass spectrometry: Via LA-ICP-MS

© 2019 The Royal Society of Chemistry. We present a novel on-line isotope dilution analysis (IDA) approach for the quantification of isotopically enriched metal labels used in immunohistochemical assisted imaging mass spectrometry. This technique advances recently reported on-line IDA for laser ablation-inductively coupled plasma mass spectrometry (LA-ICP-MS) by performing on-line reverse IDA of isotopically enriched elements commonly used as labels for antibodies. This approach allows relative quantification of biomolecules and is superior to other methods that have long acquisition times such as three-dimensional LA-ICP-MS, or when higher sample throughput is required. As a proof of concept, anti-tyrosine hydroxylase was labelled with Yb isotopes and incubated on two parallel cryocut sections of a mouse brain. IDA dependent parameters were determined by ablation of matrix-matched standards. Quantification by IDA was compared against external calibration and was a more robust method, unaffected by sensitivity changes originating from plasma drifts or spontaneous plasma fluctuations

LA-ICP-MS/MS improves limits of detection in elemental bioimaging of gadolinium deposition originating from MRI contrast agents in skin and brain tissues

© 2018 Elsevier GmbH A novel analytical method to detect the retention of gadolinium from contrast agents for magnetic resonance imaging (MRI) in tissue samples of patients is presented. It is based on laser ablation - inductively coupled plasma - triple quadrupole - mass spectrometry (LA-ICP-MS/MS). Both Gd and P were monitored with a mass shift of +16, corresponding to mono-oxygenated species, as well as Zn, Ca, and Fe on-mass. This method resulted in a significantly reduced background and improved limits of detection not only for phosphorus, but also for gadolinium. These improvements were essential to perform elemental bioimaging with improved resolution of 5 μm x 5 μm, allowing the detection of small Gd deposits in fibrotic skin and brain tumour tissue with diameters of approximately 50 μm. Detailed analyses of these regions revealed that most Gd was accompanied with P and Ca, indicating co-precipitation

Trace element geochemistry in the earliest terrestrial ecosystem, the Rhynie Chert

Acknowledgements JGTA is supported by the Natural Environment Research Council (grant NE/T003677/1). Samples were archived at the University of Aberdeen by N.H. Trewin, S.R. Fayers and C.M. Rice. Skilled technical support was provided by J. Johnston, J. Bowie, W. Ritchie and C. Taylor. We are grateful for the comments of two reviewers which improved the manuscript.Peer reviewedPublisher PD

Matching sensitivity to abundance: High resolution immuno-mass spectrometry imaging of lanthanide labels and endogenous elements in the murine brain

© 2020 The Royal Society of Chemistry. This work introduces a new method for immuno-mass spectrometry imaging via quadrupole-based laser ablation-inductively coupled plasma-mass spectrometry instruments that is matched to the abundance of elements in biological tissues. Manipulation of ion-optics and quadrupole mass filter parameters provided increased transmission of low level high-mass elements, which are typically used as labels for antibodies, at the expense of highly abundant endogenous low-mass elements. Transmission of mid-mass elements such as transition metals was only slightly affected. The implications for mass resolution and background signals are critically discussed and signal to noise ratios and imaging capabilities are compared to those obtained from a standard method. This novel approach resulted in a 6-fold improved signal to noise ratio for lanthanides that are routinely used as elemental labels for antibodies to target protein distributions in biological tissues. This increase in signal intensity, enhanced contrasts, lower limits of detection and the potential to improve spatial resolution contributed to enhanced imaging and trace analyses, as demonstrated by imaging murine brain sections of the hippocampal system and substantia nigra

Dietary zinc and the control of Streptococcus pneumoniae infection

© 2019 Eijkelkamp et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Human zinc deficiency increases susceptibility to bacterial infection. Although zinc supplementation therapies can reduce the impact of disease, the molecular basis for protection remains unclear. Streptococcus pneumoniae is a major cause of bacterial pneumonia, which is prevalent in regions of zinc deficiency. We report that dietary zinc levels dictate the outcome of S. pneumoniae infection in a murine model. Dietary zinc restriction impacts murine tissue zinc levels with distribution post-infection altered, and S. pneumoniae virulence and infection enhanced. Although the activation and infiltration of murine phagocytic cells was not affected by zinc restriction, their efficacy of bacterial control was compromised. S. pneumoniae was shown to be highly sensitive to zinc intoxication, with this process impaired in zinc restricted mice and isolated phagocytic cells. Collectively, these data show how dietary zinc deficiency increases sensitivity to S. pneumoniae infection while revealing a role for zinc as a component of host antimicrobial defences

Cooperative Model Production in Systems Design to Support Knowledge Management

The computer support of cooperation and knowledge production across socially distributed activity systems has become an important topic in the context of the discourse on „knowledge management“. The present article will draw on concepts of cultural-historical activity theory to discuss the problem of how the notion of „knowledge “ is conceptualized and implicitly implemented in computer systems to support knowledge management, often neglecting the social embeddedness of knowledge production in everyday work practices. From the point of view of cultural-historical activity theory we would propose to look upon the generation of knowledge as a process embedded in socially distributed activities that are constantly being reproduced and transformed in and between specific communities of practice. The concept of cooperative model production is highlighted as a means to mediate, not to eliminate, differences of perspectives involved in the course of systems design. Empirical results of a case study will be presented in which the Repertory-Grid has been used to visualize similarities and differences of potential users’ viewpoints and requirements in early stages of systems design

Entwicklung eines organisationsspezifischen E-Learning-Leitfadens für Dozierende – die Roadmap to E-Learning@ETH Zurich

Zunehmend stehen Dozierende bei der Planung geeigneter Lehr-Lern-Szenarien für das E-Learning vor einem unübersichtlichen Angebot an technischen und didaktischen Möglichkeiten. Zudem sind insbesondere E-Learning-Novizen unzureichend mit den institutionellen und informellen Möglichkeiten des E-Learning-Support-Netzwerks ihrer Hochschule vertraut. Dadurch können gewichtige Hindernisse für die kreative und effektive Einbindung innovativer Elemente in den Unterricht entstehen. In diesem Beitrag wird mit der „Roadmap to E-Learning@ETH Zurich“ ein handliches Werkzeug für Dozierende beschrieben, welches die Einbindung von Elementen des E-Learning in die Lehre unterstützt. Um der Gefahr einer, aus praktischer Sicht wertlosen allgemeinen Rezeptsammlung aus dem Weg zu gehen, orientiert sich die Roadmap an den lokalen Gegebenheiten der ETH. Neben Handlungsempfehlungen, praktischen Checklisten und Literaturtipps werden lokal verfügbare Ressourcen aufgezeigt: Ansprechpartner, Finanzierungsmöglichkeiten und – in Form von „lessons learned“ – gebündelte Erfahrungen Dozierender der ETH Zürich sind Beispiele für die Organisationsspezifität der Roadmap. Hierfür werden mit Methoden des Wissensmanagements bestehende Dokumente sowie Erfahrungen und Expertise innerhalb der ETH Zürich sowie von externen Kooperationspartnern systematisch aufbereitet und in einem handlichen Buch von maximal fünfzig Seiten Umfang bereit gestellt. (DIPF/Orig.

Sulzer Innotec AG: Sustainable anchoring of knowledge management in the company

Der Fall Sulzer Innotec AG veranschaulicht Meilensteine und Fallstricke auf dem Weg zu einer konkreten betrieblichen Verankerung von Wissensmanagement. Aus dem Fall lassen sich folgende Erkenntnisse für die Initiierung von Wissensmanagement gewinnen: Eine angemessene Konkretisierung von Wissensmanagement führt über den Weg einer mehrfachen Re-Definition des Themas. Verschiedene Zugänge müssen von allen relevanten Akteuren überprüft und in ihrem wechselseitigen Zusammenhang verstanden und kommuniziert werden. Dabei ist eine längerfristige Perspektive auf Wissensmanagement anzustreben, um einen nachhaltigen Veränderungsprozess zu initiieren. Es bedarf einer breit abgestützten Sensibilisierung von Beteiligten und Betroffenen. Die Zusammenarbeit mit exter¬nen wissenschaftlichen Partnern, die im Rahmen einer Begleitforschung einen interventionsorientierten Ansatz verfolgen, hat sich als prozessunterstützend erwiesen, wobei der methodischen Unterstützung von Sensibilisierungsprozessen für das Thema Wissen eine besondere Bedeutung zukam. Die Institutionalisierung eines Kernteams ermöglichte es, Akteure aus verschiedenen Unternehmensbereichen in den Prozess zu integrieren. Eine zusätzliche, strategische Verankerung des Themas über ein Steering-Committee signalisierte das Commitment des Top-Managements

Taking Actors' Perspectives Seriously: Whose Knowledge and What is Managed? Knowledge Management in a Transdisciplinary Perspective

Knowledge is often considered to be the most important intangible asset of the future. The management of knowledge is generally understood as management of data and information Consequently, most approaches see knowledge management primarily as a matter of sophisticated information technologies. In this contribution, knowledge is understood as something that is generated, transferred and reproduced in interaction processes. Hence, knowledge is an irreducible part of the interaction process itself. To assess, exchange, and eventually, manage knowledge all actors participating in a knowledge interaction process and their specific perspectives have to be taken into account. To be able to do so, a transdisciplinary perspective in indispensable in theory, method, and the implementation of knowledge management strategies and tools. A promising way to study the different actor’s perspectives is by analysing the use and role of language in knowledge management processes as proposed here