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Background: Cancer heterogeneity poses a serious challenge concerning the toxicity and adverse effects of therapeutic inhibitors, especially when it comes to combinatorial therapies that involve multiple targeted inhibitors. In particular, in non-small cell lung cancer (NSCLC), a number of studies have reported synergistic effects of drug combinations in the preclinical models, while they were only partially successful in the clinical setup, suggesting those alternative clinical strategies (with genetic background and immune response) should be considered. Herein, we investigated the antitumor effect
of cytokine-induced killer (CIK) cells in combination with ALK and PD-1 inhibitors in vitro on genetically variable NSCLC cell lines.
Methods: We co-cultured the three genetically different NSCLC cell lines NCI-H2228 (EML4-ALK), A549 (KRAS mutation), and HCC-78 (ROS1 rearrangement) with and without nivolumab (PD-1 inhibitor) and crizotinib (ALK inhibitor). Additionally, we profiled the variability of surface expression multiple immune checkpoints, the concentration of absolute dead cells, intracellular granzyme B on CIK cells using flow cytometry as well as RT-qPCR. ELISA and Western blot were performed to verify the activation of CIK cells.
Results: Our analysis showed that (a) nivolumab significantly weakened PD-1 surface expression on CIK cells without impacting other immune checkpoints or PD-1 mRNA expression, (b) this combination strategy showed an effective response on cell viability, IFN-g production, and intracellular release of granzyme B in CD3+ CD56+ CIK cells, but solely in NCI-H2228, (c) the intrinsic expression of Fas ligand (FasL) as a T-cell activation marker in CIK cells was upregulated by this additive effect, and (d) nivolumab induced Foxp3 expression in CD4+CD25+ subpopulation of CIK cells significantly increased. Taken together, we could show that CIK cells in combination with crizotinib and nivolumab can enhance the anti-tumor immune response through FasL activation, leading to increased IFN-g and granzyme B, but only in NCI-H2228 cells with EML4-ALK rearrangement. Therefore, we hypothesize that CIK therapy may be a potential alternative in NSCLC patients harboring EML4-ALK rearrangement, in addition, we support the idea that combination therapies offer significant potential when they are optimized on a patient-by-patient basis.
With the increasing demand for ultrapure water in the pharmaceutical and semiconductor industry, the need for precise measuring instruments for those applications is also growing. One critical parameter of water quality is the amount of total organic carbon (TOC). This work presents a system that uses the advantage of the increased oxidation power achieved with UV/O3 advanced oxidation process (AOP) for TOC measurement in combination with a significant miniaturization compared to the state of the art. The miniaturization is achieved by using polymer-electrolyte membrane (PEM) electrolysis cells for ozone generation in combination with UV-LEDs for irradiation of the measuring solution, as both components are significantly smaller than standard equipment. Conductivity measurement after oxidation is the measuring principle and measurements were carried out in the TOC range between 10 and 1000 ppb TOC. The suitability of the system for TOC measurement is demonstrated using the oxidation by ozonation combined with UV irradiation of defined concentrations of isopropyl alcohol (IPA).
In this paper, a gas-to-power (GtoP) system for power outages is digitally modeled and experimentally developed. The design includes a solid-state hydrogen storage system composed of TiFeMn as a hydride forming alloy (6.7 kg of alloy in five tanks) and an air-cooled fuel cell (maximum power: 1.6 kW). The hydrogen storage system is charged under room temperature and 40 bar of hydrogen pressure, reaching about 110 g of hydrogen capacity. In an emergency use case of the system, hydrogen is supplied to the fuel cell, and the waste heat coming from the exhaust air of the fuel cell is used for the endothermic dehydrogenation reaction of the metal hydride. This GtoP system demonstrates fast, stable, and reliable responses, providing from 149 W to 596 W under different constant as well as dynamic conditions. A comprehensive and novel simulation approach based on a network model is also applied. The developed model is validated under static and dynamic power load scenarios, demonstrating excellent agreement with the experimental results.
Jet engines of airplanes are designed such that in some components damage occurs and accumulates in service without being critical up to a certain level of damage. Since maintenance, repair, and component exchange are very cost-intensive, it is necessary to predict efficiently the component lifetime with high accuracy. A former developed lifetime model, based on interpolated results of aerodynamic and structural mechanics simulations, uses material parameters estimated from literature values of standard creep experiments. For improved accuracy, an experimental procedure is developed for the characterization of the short-time creep behavior, which is relevant for the operation of turbine blades of jet engines. To consider microstructural influences resulting from the manufacturing of thin-walled single crystal turbine blades, small-scale specimens from used turbine blades are extracted and tested in short- and medium-time creep experiments. Based on experimental results and literature values, a creep model, which describes the fracture behavior for a wide range of creep loads, is calibrated and is now used for the lifetime prediction of turbine blades under real loading conditions.
For research in audiovisual interview archives often it is not only of interest what is said but also how. Sentiment analysis and emotion recognition can help capture, categorize and make these different facets searchable. In particular, for oral history archives, such indexing technologies can be of great interest. These technologies can help understand the role of emotions in historical remembering. However, humans often perceive sentiments and emotions ambiguously and subjectively. Moreover, oral history interviews have multi-layered levels of complex, sometimes contradictory, sometimes very subtle facets of emotions. Therefore, the question arises of the chance machines and humans have capturing and assigning these into predefined categories. This paper investigates the ambiguity in human perception of emotions and sentiment in German oral history interviews and the impact on machine learning systems. Our experiments reveal substantial differences in human perception for different emotions. Furthermore, we report from ongoing machine learning experiments with different modalities. We show that the human perceptual ambiguity and other challenges, such as class imbalance and lack of training data, currently limit the opportunities of these technologies for oral history archives. Nonetheless, our work uncovers promising observations and possibilities for further research.
Während sich die unternehmerische Arbeitswelt immer mehr in Richtung Agilität verschiebt, verharrt das IT-Controlling noch in alten, klassischen Strukturen. Diese Arbeit untersucht die Fragestellung, ob und inwieweit agile Ansätze im IT-Controlling eingesetzt werden können. Dieser Beitrag ist eine modifizierte Version des in der Zeitschrift „HMD Praxis der Wirtschaftsinformatik“ (https://link.springer.com/article/10.1365/s40702-022-00837-0) erschienenen Artikels „Agiles IT-Controlling“.
Agiles IT-Controlling
(2022)
Während im IT-Projektmanagement agile Methoden seit vielen Jahren in der Praxis Zuspruch finden, werden im IT-Controlling überwiegend noch klassische Methoden eingesetzt. Der Beitrag untersucht die Fragestellung, ob und wie die im IT-Controlling eingesetzten Methoden auch agilen Paradigmen folgen und Methoden des agilen IT-Projektmanagements adaptiert werden können.
The following work presents algorithms for semi-automatic validation, feature extraction and ranking of time series measurements acquired from MOX gas sensors. Semi-automatic measurement validation is accomplished by extending established curve similarity algorithms with a slope-based signature calculation. Furthermore, a feature-based ranking metric is introduced. It allows for individual prioritization of each feature and can be used to find the best performing sensors regarding multiple research questions. Finally, the functionality of the algorithms, as well as the developed software suite, are demonstrated with an exemplary scenario, illustrating how to find the most power-efficient MOX gas sensor in a data set collected during an extensive screening consisting of 16,320 measurements, all taken with different sensors at various temperatures and analytes.
The design of a fully superconducting wind power generator is influenced by several factors. Among them, a low number of pole pairs is desirable to achieve low AC losses in the superconducting stator winding, which greatly influences the cooling system design and, consecutively, the efficiency of the entire wind power plant. However, it has been identified that a low number of pole pairs in a superconducting generator tends to greatly increase its output voltage, which in turn creates challenging conditions for the necessary power electronic converter. This study highlights the interdependencies between the design of a fully superconducting 10 MW wind power generator and the corresponding design of its power electronic converter.
Cytokine-induced killer cells (CIK) in combination with dendritic cells (DCs) have shown favorable outcomes in renal cell carcinoma (RCC), yet some patients exhibit recurrence or no response to this therapy. In a broader perspective, enhancing the antitumor response of DC-CIK cells may help to address this issue. Considering this, herein, we investigated the effect of anti-CD40 and anti-CTLA-4 antibodies on the antitumor response of DC-CIK cells against RCC cell lines. Our analysis showed that, a) anti-CD40 antibody (G28.5) increased the CD3+CD56+ effector cells of CIK cells by promoting the maturation and activation of DCs, b) G28.5 also increased CTLA-4 expression in CIK cells via DCs, but the increase could be hindered by the CTLA-4 inhibitor (ipilimumab), c) adding ipilimumab was also able to significantly increase the proportion of CD3+CD56+ cells in DC-CIK cells, d) anti-CD40 antibodies predominated over anti-CTLA-4 antibodies for cytotoxicity, apoptotic effect and IFN-g secretion of DC-CIK cells against RCC cells, e) after ipilimumab treatment, the population of Tregs in CIK cells remained unaffected, but ipilimumab combined with G28.5 significantly reduced the expression of CD28 in CIK cells. Taken together, we suggest that the agonistic anti-CD40 antibody rather than CTLA-4 inhibitor may improve the antitumor response of DC-CIK cells, particularly in RCC. In addition, we pointed towards the yet to be known contribution of CD28 in the crosstalk between anti-CTLA-4 and CIK cells.
The white ground crater by the Phiale Painter (450–440 BC) exhibited in the “Pietro Griffo” Archaeological Museum in Agrigento (Italy) depicts two scenes from Perseus myth. The vase is of utmost importance to archaeologists because the figures are drawn on a white background with remarkable daintiness and attention to detail. Notwithstanding the white ground ceramics being well documented from an archaeological and historical point of view, doubts concerning the compositions of pigments and binders and the production technique are still unsolved. This kind of vase is a valuable rarity, the use of which is documented in elitist funeral rituals. The study aims to investigate the constituent materials and the execution technique of this magnificent crater. The investigation was carried out using non-destructive and non-invasive techniques in situ. Portable X-ray fluorescence and Fourier-transform total reflection infrared spectroscopy complemented the use of visible and ultraviolet light photography to get an overview and specific information on the vase. The XRF data were used to produce false colour maps showing the location of the various elements detected, using the program SmART_scan. The use of gypsum as the material for the white ground is an important result that deserves to be further investigated in similar vases.
Research has identified nudging as a promising and effective tool to improve healthy eating behavior in a cafeteria setting. However, it remains unclear who is and who is not “nudgeable” (susceptible to nudges). An important influencing factor at the individual level is nudge acceptance. While some progress has been made in determining influences on the acceptance of healthy eating nudges, research on how personal characteristics (such as the perception of social norms) affect nudge acceptance remains scarce. We conducted a survey on 1032 university students to assess the acceptance of nine different types of healthy eating nudges in a cafeteria setting with four influential factors (social norms, health-promoting collaboration, responsibility to promote healthy eating, and procrastination). These factors are likely to play a role within a university and a cafeteria setting. The present study showed that key influential factors of nudge acceptance were the perceived responsibility to promote healthy eating and health-promoting collaboration. We also identified three different student clusters with respect to nudge acceptance, demonstrating that not all nudges were accepted equally. In particular, default, salience, and priming nudges were at least moderately accepted regardless of the degree of nudgeability. Our findings provide useful policy implications for nudge development by university, cafeteria, and public health officials. Recommendations are formulated for strengthening the theoretical background of nudge acceptance and the susceptibility to nudges.
This paper explores the role of artificial intelligence (AI) in elite sports. We approach the topic from two perspectives. Firstly, we provide a literature based overview of AI success stories in areas other than sports. We identified multiple approaches in the area of Machine Perception, Machine Learning and Modeling, Planning and Optimization as well as Interaction and Intervention, holding a potential for improving training and competition. Secondly, we discover the present status of AI use in elite sports. Therefore, in addition to another literature review, we interviewed leading sports scientist, which are closely connected to the main national service institute for elite sports in their countries. The analysis of this literature review and the interviews show that the most activity is carried out in the methodical categories of signal and image processing. However, projects in the field of modeling & planning have become increasingly popular within the last years. Based on these two perspectives, we extract deficits, issues and opportunities and summarize them in six key challenges faced by the sports analytics community. These challenges include data collection, controllability of an AI by the practitioners and explainability of AI results.
The implementation of the Sustainable Development Goals (SDGs) and the conservation and protection of nature are among the greatest challenges facing urban regions. There are few approaches so far that link the SDGs to natural diversity and related ecosystem services at the local level and track them in terms of increasing sustainable development at the local level. We want to close this gap by developing a set of indicators that capture ecosystem services in the sense of the SDGs and which are based on data that are freely available throughout Germany and Europe. Based on 10 SDGs and 35 SDG indicators, we are developing an ecosystem service and biodiversity-related indicator set for the evaluation of sustainable development in urban areas. We further show that it is possible to close many of the data gaps between SDGs and locally collected data mentioned in the literature and to translate the universal SDGs to the local level. Our example develops this set of indicators for the Bonn/Rhein-Sieg metropolitan area in North Rhine-Westphalia, Germany, which comprises both rural and densely populated settlements. This set of indicators can also help improve communication and plan sustainable development by increasing transparency in local sustainability, implementing a visible sustainability monitoring system, and strengthening the collaboration between local stakeholders.
Due to the COVID-19 pandemic, health education programs and workplace health promotion (WHP) could only be offered under difficult conditions, if at all. In Germany for example, mandatory lockdowns, working from home, and physical distancing have led to a sharp decline in expenditure on prevention and health promotion from 2019 to 2020. At the same time, the pandemic has negatively affected many people’s mental health. Therefore, our goal was to examine audiovisual stimulation as a possible measure in the context of WHP, because its usage is contact-free, time flexible, and offers, additionally, voice-guided health education programs. In an online survey following a cross-sectional single case study design with 393 study participants, we examined the associations between audiovisual stimulation and mental health, work engagement, and burnout. Using multiple regression analyses, we could identify positive associations between audiovisual stimulation and mental health, burnout, and work engagement. However, longitudinal data are needed to further investigate causal mechanisms between mental health and the use of audiovisual stimulation. Nevertheless, especially with regard to the pandemic, audiovisual stimulation may represent a promising measure for improving mental health at the workplace.
Ausrangierte Nachrichten
(2022)
Wichtige Nachrichten finden nicht ihre Bestimmung, nämlich das politisch interessierte und gesellschaftlich aufgeschlossene Publikum. Man kann diesen Vorgang als Agenda Cutting bezeichnen. Der Beitrag stellt die wichtigsten theoretischen Positionen zu diesem bislang noch wenig erforschten Phänomen dar, präsentiert wichtige Studienergebnisse und auch eigene empirische Ergebnisse zu innerredaktionellen Entscheidungsfindungsprozessen, bei denen Themen von der Agenda gestrichen werden. Zuletzt wird auch die Rolle des Publikums als Akteur beim Vorgang des Agenda Cuttings kritisch beleuchtet, die man als »news ignorance« beschreiben könnte.[1]
Die schleichende Abschaffung der Lernmittelfreiheit in den deutschen Bundesländern steht im Jahr 2022 auf Platz 1 der Top Ten der ›Vergessenen Nachrichten‹, die die Initiative Nachrichtenaufklärung (INA) e.V. jedes Jahr in die Öffentlichkeit lanciert. Der Chef des Fernsehnachrichtenmagazins Tagesthemen und stellvertretender Chefredakteur von ARD-Aktuell, Helge Fuhst, konzedierte in der Mediensendung eines öffentlich-rechtlichen Radiosenders, dass er dieses Thema für hochrelevant halte und es tatsächlich in seiner TV-Nachrichtensendung nicht behandelt worden sei. »Was das Schwierigste ist, ist tatsächlich Themen wegzulassen«, so Fuhst. »Es schmerzt uns jeden Tag, wenn wir Themen weglassen müssen. Es gibt wenige Tage im Laufe des Jahres, wo wir absolut keine Idee haben, was wir in die Sendung nehmen sollen« (WDR 2022).
Der Vorgang der Nachrichtenselektion ist redaktionelle Routine, und zu dieser Routine zählt auch, Themen wegzulassen, auszusortieren, fortzuschmeißen. Wenn dieser negative Prozess intentional erfolgt, kann man auch von Agenda Cutting sprechen. Dieser kommunikationswissenschaftliche Begriff beschreibt eine eigene Form redaktioneller Routine, die bislang nur wenig untersucht worden ist und deren Mechanismen mit ihrem erheblichen Einfluss auf die öffentliche Meinungsbildung dringend unter das Seziermesser der Medienforschung gehören.
Auswirkungen einer anhaltenden, inflationären Geldpolitik in der Eurozone auf den privaten Sparer
(2022)
Die vorliegende Bachelorarbeit setzt sich kritisch mit den Auswirkungen einer anhaltenden, inflationären Geldpolitik in der Eurozone auf den privaten Sparer auseinander. Im Rahmen dieser Arbeit wird aufgezeigt, wie die starke Erhöhung der Geldmenge Einfluss auf die Möglichkeiten und Entscheidungen des Sparers hat und wie weit eine solche Geldpolitik mit den Interessen des Sparers vereinbar ist.
In March 2020, the world was hit by the coronavirus disease (COVID‐19) pandemic which led to all‐embracing measures to contain its spread. Most employees were forced to work from home and take care of their children because schools and daycares were closed. We present data from a research project in a large multinational organisation in the Netherlands with monthly quantitative measurements from January to May 2020 (N = 253–516), enriched with qualitative data from participants' comments before and after telework had started. Growth curve modelling showed major changes in employees' work‐related well‐being reflected in decreasing work engagement and increasing job satisfaction. For work‐non‐work balance, workload and autonomy, cubic trends over time were found, reflecting initial declines during crisis onset (March/April) and recovery in May. Participants' additional remarks exemplify that employees struggled with fulfilling different roles simultaneously, developing new routines and managing boundaries between life domains. Moderation analyses demonstrated that demographic variables shaped time trends. The diverging trends in well‐being indicators raise intriguing questions and show that close monitoring and fine‐grained analyses are needed to arrive at a better understanding of the impact of the crisis across time and among different groups of employees.
The backdated research dedicated to digital entrepreneurship education is immense, which makes it difficult to create an overview. Conversely, forward-thinking bibliometric visualization mapping and clustering can assist in visualizing and structuring difficult research literature. Hence, the goal of this mapping visualization study is to thoroughly discover and create clusters of EE to convey a taxonomic structure that can oblige as a basis for upcoming research. The analyzed data, which is drawn from Google Scholar through Publish or Perish tool, contain 1000 documents published between 2007 and 2022. This taxonomy should generate stronger bonds with digital entrepreneurial education research; on the other, it should stand in international research association to boost both interdisciplinary digital entrepreneurial education and its influence on a universal basis. This work strengthens student’s understanding of current digital entrepreneurial education research by classifying and decontaminating the most powerful knowledgeable relationship among its contributions and contributors. The bibliographic analysis includes ‘citation network’, ‘author’s research area’ and ‘paper content’ regarding the desired topic. In this paper, the above three mentioned terms are integrated which produces a bibliographic model of authors, titles of their papers, keywords and abstract by using Harzing’s Publish or Perish tool for extracting data from Google Scholar and further using VOSViewer to visualize networking map of co-authorship and term co-occurrence to administer the data for an instinctive and appropriate understanding of university students concerning ‘digital entrepreneurial intention’ research. This paper uses bibliometric analysis to analyze the keyword co-occurrence and co-authorship and VOSViewer is used for visualization.
There is an unmet need for the development and validation of biomarkers and surrogate endpoints for clinical trials in propionic acidemia (PA) and methylmalonic acidemia (MMA). This review examines the pathophysiology and clinical consequences of PA and MMA that could form the basis for potential biomarkers and surrogate endpoints. Changes in primary metabolites such as methylcitric acid (MCA), MCA:citric acid ratio, oxidation of 13C-propionate (exhaled 13CO2), and propionylcarnitine (C3) have demonstrated clinical relevance in patients with PA or MMA. Methylmalonic acid, another primary metabolite, is a potential biomarker, but only in patients with MMA. Other potential biomarkers in patients with either PA and MMA include secondary metabolites, such as ammonium, or the mitochondrial disease marker, fibroblast growth factor 21. Additional research is needed to validate these biomarkers as surrogate endpoints, and to determine whether other metabolites or markers of organ damage could also be useful biomarkers for clinical trials of investigational drug treatments in patients with PA or MMA. This review examines the evidence supporting a variety of possible biomarkers for drug development in propionic and methylmalonic acidemias.