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Adult muscle carnitine palmitoyltransferase (CPT) II deficiency is a rare autosomal recessive disorder of long-chain fatty acid metabolism. It is typically associated with recurrent episodes of exercise-induced rhabdomyolysis and myoglobinuria, in most cases caused by a c.338C > T mutation in the CPT2 gene. Here we present the pedigree of one of the largest family studies of CPT II deficiency caused by the c.338C > T mutation, documented so far. The pedigree comprises 24 blood relatives
of the index patient, a 32 year old female with genetically proven CPT II deficiency. In total, the mutation was detected in 20 family members, among them five homozygotes and 15 heterozygotes. Among all homozygotes, first symptoms of CPT II deficiency occurred during childhood. Additionally, two already deceased relatives of the index patient were carriers of at least one copy of the genetic variant, revealing a remarkably high prevalence of the c.338C > T mutation within the tested family. Beside the index patient, only one individual had been diagnosed with CPT II deficiency prior to this study and three cases of CPT II deficiency were newly detected by this family study, pointing
to a general underdiagnosis of the disease. Therefore, this study emphasizes the need to raise awareness of CPT II deficiency for correct diagnosis and accurate management of the disease.
Through mandatory ESG (environmental, social, governance) reporting large companies must disclose their ESG activities showing how sustainability risks are incorporated in their decision-making and production processes. This disclosure obligation, however, does not apply to small and medium-sized enterprises (SME), creating a gap in the ESG dataset. Banks are therefore required to collect sustainability data of their SME customers independently to ensure complete ESG integration in the risk analysis process for loans. In this paper, we examine ESG risk analysis through a smart science approach laying the focus on possible value outcomes of sustainable smart services for banks as well as for their (SME) customers. The paper describes ESG factors, how services can be derived from them, targeted metrics of ESG and an ESG Service Creation Framework (business ecosystem building, process model, and value creation). The description of an exemplary use case highlighting the necessary ecosystem for service creation as well as the created value concludes the paper.
Modeling the dynamic of breath methane concentration profiles during exercise on an ergometer
(2015)
Smart services disrupt business models and have the potential to stimulate the circular economy transition of regions, enabling an environmentally friendly atmosphere for sustainable and innovation-driven growth of regions. Although smart services are powerful means for deploying circular economy goals in industrial practices, there is little systematic guidance on how the adoption of smart services could improve resource efficiency and stimulate smart regional innovation-driven growth, enabled through circular design. Implemented in the scope of Vorarlberg’s smart specialization strategy, this paper contributes to the literature on the circular economy and regional innovation-driven growth by assessing critical factors of the value creation and value capture implemented within the scope of the quadruple helix system. By identifying the main challenges and opportunities of collaborative value creation and value capture in setting-up smart circular economy strategies and by assessing the role of innovation actors within the quadruple helix innovation system, the study provides recommendations and set of guidelines for managers and public authorities in managing circular transition. Finally, based on the analysis of the role of actors in creating shared value and scaling-up smart circular economy practices in the quadruple helix innovation systems, the paper investigates the role of banks as enablers of circular economy innovation-driven regional growth and smart value creation.
Complementarities and synergies of quadruple helix innovation design in smart city development
(2020)
Increased urbanization trends are stimulating regional needs to support transitions from urban environments to smart cities, using its holistic perspective as a source to innovation. Strong relations between smart cities, urban and regional development, are getting increased attention both at policy and implementation level, providing fertile ground for execution of the new European policy frameworks that supports quadruple helix approaches to innovation. Smart specialization strategies (RIS3) encompass such initiatives, placing ICT and collaboration between academia, industry, government, and citizen at the center of urban innovation. However, there is still lack of research on effects of such approaches to innovation, involving both quadruple helix clusters and ICT in utilizing innovation potentials for developing smart cities. This study aims to increase the understanding on how quadruple helix urban innovation strengthens competitiveness of regions by improving its local smart areas – RIS3. We identified smart specialization patterns and applied comparative benchmark between nine smallmedium sized urban regions in Central Europe. Building on these results, the study provides an overview of the effects of RIS3 strategies implemented through quadruple helix innovation clusters on competitiveness of regions and Smart City development.
A covariance matrix self-adaptation evolution strategy for optimization under linear constraints
(2018)
A multi-recombinative active matrix adaptation evolution strategy for constrained optimization
(2019)
Analysis of the (μ/μI,λ)-CSA-ES with repair by projection applied to a conically constrained problem
(2019)
A model is presented that allows for the calculation of the success probability by which a vanilla Evolution Strategy converges to the global optimizer of the Rastrigin test function. As a result a population size scaling formula will be derived that allows for an estimation of the population size needed to ensure a high convergence security depending on the search space dimensionality.
Why do some countries assign a major role to wind energy in decarbonizing their electricity systems, while others are much less committed to this technology? We argue that processes of (de-)legitimation, driven by discourse coalitions who strategically employ certain storylines in public debates, provide part of the answer. To illustrate our approach, we comparatively investigate public discourses surrounding wind energy in Austria and Switzerland, two countries that differ strongly in wind energy deployment. By combining a qualitative content analysis and a discourse network analysis of 808 newspaper articles published 2010–2020, we identify four distinct sets of storylines used to either delegitimize or legitimize the technology. Our study indicates that low deployment rates in Switzerland can be related to the prominence of delegitimizing storylines in the public discourse, which result in a rather low socio-political acceptance of wind energy. In Austria, by contrast, there is more consistent support for wind energy by discourse coalitions using a broad set of legitimizing storylines. By bridging the related but separate literatures of technology legitimacy and social acceptance, our study contributes to a better understanding of socio-political conflict and divergence in low-carbon technological pathways.
Im vorliegenden Paper wird ein Vergleich zwischen Produktions-und Simulationsdaten präsentiert welches im Rahmen einer größeren Initiative zur Verwendung von Shopfloor Daten bei einem Projektpartner in der Automobilindustrie umgesetzt wurde. In diesem Projekt wurden die Daten die während der Füllbildsimulation entstehen mit den Daten aus der finalen Werkzeugabnahme verglichen um zu analysieren, wie genau diese miteinander über einstimmen. Je besser die Simulation ist, desto schneller kann der gesamte Werkzeugentwicklungsprozess abgewickelt werden, welcher als Kernprozess massives Einsparungspotenzial und damit Wettbewerbsvorteil mit sich bringt.
The usage of data gathered for Industry 4.0 and smart factory scenarios continues to be a problem for companies of all sizes. This is often the case because they aim to start with complicated and time-intensive Machine Learning scenarios. This work evaluates the Process Capability Analysis (PCA) as a pragmatic, easy and quick way of leveraging the gathered machine data from the production process. The area of application considered is injection molding. After describing all the required domain knowledge, the paper presents an approach for a continuous analysis of all parts produced. Applying PCA results in multiple key performance indicators that allow for fast and comprehensible process monitoring. The corresponding visualizations provide the quality department with a tool to efficiently choose where and when quality checks need to be performed. The presented case study indicates the benefit of analyzing whole process data instead of considering only selected production samples. The use of machine data enables additional insights to be drawn about process stability and the associated product quality.
With Cloud Computing and multi-core CPUs parallel computing resources are becoming more and more affordable and commonly available. Parallel programming should as well be easily accessible for everyone. Unfortunately, existing frameworks and systems are powerful but often very complex to use for anyone who lacks the knowledge about underlying concepts. This paper introduces a software framework and execution environment whose objective is to provide a system which should be easily usable for everyone who could benefit from parallel computing. Some real-world examples are presented with an explanation of all the steps that are necessary for computing in a parallel and distributed manner.
Breath analysis holds great promise for real-time and non-invasive medical diagnosis. Thus, there is a considerable need for simple-in-use and portable analyzers for rapid detection of breath indicators for different diseases in their early stages. Sensor technology meets all of these demands. However, miniaturized breath analyzers require adequate breath sampling methods. In this context, we propose non-contact sampling; namely the collection of breath samples by exhalation from a distance into a miniaturized collector without bringing the mouth into direct contact with the analyzing device. To evaluate this approach different breathing maneuvers have been tested in a real-time regime on a cohort of 23 volunteers using proton transfer reaction mass spectrometry. The breathing maneuvers embraced distinct depths of respiration, exhalation manners, size of the mouth opening and different sampling distances. Two inhalation modes (normal, relaxed breathing and deep breathing) and two exhalation manners (via smaller and wider lips opening) forming four sampling scenarios were selected. A sampling distance of approximately 2 cm was found to be a reasonable trade-off between sample dilution and requirement of no physical contact of the subject with the analyzer. All four scenarios exhibited comparable measurement reproducibility spread of around 10%. For normal, relaxed inspiration both dead-space and end-tidal phases of exhalation lasted approximately 1.5 s for both expiration protocols. Deep inhalation prolongs the end-tidal phase to about 3 s in the case of blowing via a small lips opening, and by 50% when the air is exhaled via a wide one. In conclusion, non-contact breath sampling can be considered as a promising alternative to the existing breath sampling methods, being relatively close to natural spontaneous breathing.
Product ion distributions resulting from the primary reactions of H3O+ with nine D-labeled volatile organic compounds and the subsequent sequential reactions with H2O have been determined using a Proton Transfer Reaction Time of Flight Mass Spectrometer (PTR-TOF 8000 (IONICON Analytik GmbH)) at various reduced electric field (E/N) values ranging from 80 up to 150 Td and for two different absolute humidity levels of air sample < 0.1% and 5%. The specific D-labeled compounds used in this study are acetone-d6, toluene-d8, benzene-d6, ethanol-d (C2H5OD), ethanol-d2 (CH3CD2OH), ethanol-d6, 2-propanol-d8, 2-propanol-d3 (CD3CH(OH)CH3), and isoprene-d5 (CH2CHC(CD2)CD3). With the exception of the two 2-propanol compounds, non-dissociative proton transfer is the dominant primary reaction pathway. For 2-propanol-d8 and 2-propanol-d3 the major primary reaction channel involved is dissociative proton transfer. However, unlike their undeuterated counterparts, the primary product ions undergo subsequent deuterium/hydrogen isotope exchange reactions with the ever present water in the drift tube, the extent of which of course depends on the humidity within that tube. This exchange leads to the generation of various isotopologue product ions, the product ion branching percentages of which are also
dependent on the humidity in the drift tube. This results in complex mass spectra and the distribution of product ions leads to issues of reduced sensitivity and accuracy. However, the effect of D/H exchange considerably varies between the compounds under study. In the case of acetone-d6 it is very weak (<1%), because the exchange process is not facile when the deuterium is in the methyl functional group. In comparison, the H3O+/ benzene-d6 (C6D6) reaction and sequential reactions with water result in the production of the isotopologue ions C6Dn(H7-n)+ (where n = 0–6). Changing the value of E/N and/or the humidity in the drift tube considerably affects the amount of the isotope exchange reactions and hence the resulting sequential product ion distributions. An important conclusion of the findings from this work is that care must be taken in the choice of an exogenous deuterated compound for use in breath pharmacokinetic studies using proton transfer reaction mass spectrometry; otherwise the resulting D/H exchange processes impose interpretative problems.
© 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).
Stability of selected volatile breath constituents in Tedlar, Kynar and Flexfilm sampling bags
(2013)
Blood and breath profiles of volatile organic compounds in patients with end-stage renal disease
(2014)
Breath analysis offers a non-invasive and rapid diagnostic method for detecting various volatile organic compounds that could be indicators for different diseases, particularly metabolic disorders including type 2 diabetes mellitus. The development of type 2 diabetes mellitus is closely linked to metabolic dysfunction of adipose tissue and adipocytes. However, the VOC profile of human adipocytes has not yet been investigated. Gas chromatography with mass spectrometric detection and head-space needle trap extraction (two-bed Carbopack X/Carboxen 1000 needle traps) were applied to profile VOCs produced and metabolised by human Simpson Golabi Behmel Syndrome adipocytes. In total, sixteen compounds were identified to be related to the metabolism of the cells. Four sulphur compounds (carbon disulphide, dimethyl sulphide, ethyl methyl sulphide and dimethyl disulphide), three heterocyclic compounds (2-ethylfuran, 2-methyl-5-(methyl-thio)-furan, and 2-pentylfuran), two ketones (acetone and 2-pentanone), two hydrocarbons (isoprene and n-heptane) and one ester (ethyl acetate) were produced, and four aldehydes (2-methyl-propanal, butanal, pentanal and hexanal) were found to be consumed by the cells of interest. This study presents the first profile of VOCs formed by human adipocytes, which may reflect the activity of the adipose tissue enzymes and provide evidence of their active role in metabolic regulation. Our data also suggest that a previously reported increase of isoprene and sulphur compounds in diabetic patients may be explained by their production by adipocytes. Moreover, the unique features of this profile, including a high emission of dimethyl sulphide and the production of furan-containing VOCs, increase our knowledge about metabolism in adipose tissue and provide diagnostic potential for future applications.
Purpose: Although there is an apparent potential in using data for advanced services in manufacturing environments, SMEs are reluctant to share data with their ecosystem partners, which prevents them from leveraging this potential. Therefore, the purpose of this paper is to analyse the reasons behind these resistances. The argumentation paves the way for elaborating countermeasures that are adequate for the specific situation and the typical capabilities of SMEs.
Design/Methodology/Approach: The analysis is based on literature research and in-depth interviews with management representatives of 15 companies in manufacturing service ecosystems. Half of these are manufacturers and the other half technology or service providers for manufacturers. They are SMEs or partly larger companies operating in structures that are typical for SMEs.
Findings: Data sharing hurdles are investigated in the five dimensions, 1. quantifying the value of data, 2. willingness to share data and trust, 3. organizational culture and mindset, 4. legal aspects, and 5. security and privacy. The ability to quantify the value of data is a necessary but not sufficient precondition for data sharing, which must be enabled by adequate measures in the other four dimensions.
Originality/Value: The findings of this empirical study and the solution approach provide an SME-specific framework to analyze hurdles that must be overcome for sharing data in an ecosystem.
Manufacturing SMEs can apply the framework to overcome the hurdles by specific insights and solution approaches. Furthermore, the analysis illustrates the future research direction of the project towards a comprehensive solution approach for data sharing in a manufacturing ecosystem.
Towards a strategic management framework for engineering of organizational robustness and resilience
(2020)
Post-operative isoflurane has been observed to be present in the end-tidal breath of patients who have undergone major surgery, for several weeks after the surgical procedures. A major new noncontrolled, non-randomized, and open-label approved study will recruit patients undergoing various surgeries under different inhalation anaesthetics, with two key objectives, namely to record the washout characteristics following surgery, and to investigate the influence of a patient’s health and the duration and type of surgery on elimination. In preparation for this breath study using proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS), it is important to identify first the analytical product ions that need to be monitored and under what operating conditions. In this first paper of this new research programme, we present extensive PTR-TOF-MS studies of three major
anaesthetics used worldwide, desflurane (CF3CHFOCHF2), sevoflurane ((CF3)2CHOCH2F), and isoflurane (CF3CHClOCHF2) and a fourth one, which is used less extensively, enflurane (CHF2OCF2CHFCl), but is of interest because it is an isomer of isoflurane. Product ions are identified as a function of reduced electric field (E/N) over the range of approximately 80 Td to 210 Td, and the effects of operating the drift tube under ‘normal’ or ‘humid’ conditions on the intensities of the product ions are presented. To aid in the analyses, density functional theory (DFT) calculations of the proton affinities and the gas-phase basicities of the anaesthetics have been determined. Calculated energies for the ion-molecule reaction pathways leading to key product ions, identified as ideal for monitoring the inhalation anaesthetics in breath with a high sensitivity and selectivity, are also presented.
Towards a high productivity automatic analysis framework for classification. An initial study
(2013)
Blood flow and ventilatory flow strongly influence the concentrations of volatile organic compounds (VOCs) in exhaled breath. The physicochemical properties of a compound (e.g., water solubility) additionally determine if the concentration of the compound in breath reflects the alveolar concentration, the concentration in the upper airways, or a mixture of both. Mathematical modeling based on mass balance equations helps to understand how measured breath concentrations are related to their corresponding blood concentrations and physiological parameters, such as metabolic rates and endogenous production rates. In addition, the influence of inhaled compounds on their exhaled concentrations can be quantified and appropriate correction formulas can be derived. Isoprene and acetone, two endogenous VOCs with very different water solubility, have been modeled to explain the essential features of their behavior in breath. This chapter introduces the theory of physiological modeling of exhaled VOCs, with examples of isoprene and acetone.
Small and medium-sized enterprises often face resource deficits and there- fore depend on cooperating with other actors to stay innovative in a competitive environment. Establishing and maintaining actual co-creation and service inter- action strategies however is challenging. A reason for this is the complexity of finding methodologies and tools to create valuable outcome and the lack of knowledge of collaboration toolsets, also in virtual environments. This paper introduces an Innovation-Method-Framework consisting of innovation methods for increased service interaction and value co-creation among service stakeholders. Also, toolsets for the framework’s practical application are provided.
To create a map of an unknown area, autonomous robots must follow a strategy to explore the area without knowing the optimal paths to reduce the time needed to map the whole area. To reduce the time to accomplish this task, multiple robots can work together to create a map in a more efficient way. However, without proper coordination, the time a team of autonomous robots needs to explore the unknown area can exceed the time needed by a single robot. To counteract the challenges, a shared infrastructure is needed which extracts useful information for the individual robots out of the shared information of all robots so the exploration can be coordinated. These measures introduce new challenges to the system, concerning the load of the communication infrastructure as well as the overall task of exploring and mapping becoming dependent on the correct communication and robustness of the shared team infrastructure. Therefore, the amount of communication and dependency of each individual robot of the rest of the other robots of the team must be reduced to ensure that the robots can continue working even if the communication with the shared infrastructure fails.
Creating a schedule to perform certain actions in a realworld environment typically involves multiple types of uncertainties. To create a plan which is robust towards uncertainties, it must stay flexible while attempting to be reliable and as close to optimal as possible. A plan is reliable if an adjustment to accommodate for a new requirement causes only a few disruptions. The system needs to be able to adapt to the schedule if unforeseen circumstances make planned actions impossible, or if an unlikely event would enable the system to follow a better path. To handle uncertainties, the used methods need to be dynamic and adaptive. The planning algorithms must be able to re-schedule planned actions and need to adapt the previously created plan to accommodate new requirements without causing critical disruptions to other required actions.