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Open Source Simulation for Compression Analysis of Corrugated Boards
Get PDFIn the packaging industry, corrugated boards are widely used due to many factors like biodegradability, a high strength-to-weight ratio, and also ease of manufacturing. In this study, the finite element analysis of corrugated cardboards under the flat compression test was performed using the open source FEA software Salome-meca. A corrugated board consists of a flute sandwiched between a top and bottom liner. This study was performed with the help of Python scripting in order to iteratively perform many studies by varying the geometric shape of the flute. The pressure distribution along the top and the bottom liner was analyzed. The load–deflection curve for the corrugated cardboard was also analyzed as a part of this study. The boundary condition and the loading condition were chosen in such a way as to correctly represent the situation in real life using the flat crush test in the lab. The contact zone was identified a priori and defined during the preparation of the study. Finally, Code-Aster (the solver utilized by Salome-Meca) was used to solve the finite element solution to the problem
Combining microcosm biodegradation and reactive transport modeling to explore the feasibility of ATES-bioremediation approaches
Get PDFThis study presents a process-based model analysis of non-isothermal biodegradation of chlorinated ethenes in batch microcosm setups and field-scale remediation, combining Aquifer Thermal Energy Storage with in situ bioremediation (ATES-ISB). The features of the proposed modeling framework include: (i) kinetic multi-phase mass transfer and temperature-dependent biodegradation in batch systems, and (ii) multi-dimensional non-isothermal fluid flow, heat transport, and contaminant transport in a physically and chemically heterogeneous aquifer combined with temperature-dependent microbial kinetics. The model was used to analyze an experimental microcosm dataset of temperature-dependent reductive dehalogenation of chlorinated ethenes, from which maximum specific degradation rates were derived. A scenario modeling investigation is presented, considering an ATES-ISB intervention in an aquifer contaminated with trichloroethene, where heated groundwater is injected and lactate is delivered to stimulate in situ microbial activity and contaminant transformation. Four scenario parameters were varied to identify the optimal conditions for efficient bioremediation. High lactate concentrations and temperatures at 20°C and 30°C led to more complete transformation of chlorinated ethenes in the considered heterogeneous aquifer system. Furthermore, the pumping rate and the natural groundwater flow velocity were found to control the delivery of heated water and solutes, including lactate, in the aquifer. The outcomes of the scenario simulations performed in this study are useful for designing non-isothermal bioremediation interventions in groundwater systems polluted with organic contaminants
Rating-Meldungen europäischer Staaten und Werteffekte bei US-Banken: Eine Note zur Interdependenz globaler Kapitalmärkte
Get PDFIm Zuge der europäischen Schuldenkrise stellt sich die Frage, ob sich das Banken- und Finanzsystem der USA durch Ansteckungseffekte ebenso in Gefahr befindet. Vor dem Hintergrund zahlreicher Downgradings europäischer Staaten in den vergangenen Jahren werden im vorliegenden Beitrag Werteffekte von Rating-Meldungen auf US-Banken untersucht. Es zeigt sich, dass negative Meldungen signifikant abnormale Kursreaktionen hervorrufen, wovon besonders US-Großbanken mit hohem Risiko-Exposure gegenüber europäischen Krisenstaaten betroffen sind. Positive Meldungen ziehen dagegen keinerlei Effekte nach sich. Die Resultate belegen, dass die Konsequenzen der Schuldenkrise sich nicht allein auf Europa beschränken, sondern dass Hilfspakete für europäische Staaten auch die Finanzsysteme in Ländern anderer Kontinente stützen können
Cabanel, Patrick: L’école du peuple? Histoire d’une hypocrisie sociale, 128 S., PUR, Rennes 2023.
Get PDFDer französische Religionshistoriker Patrick Cabanel hat mit „L'Ecole du Peuple“ eine nur 128 Seiten starke Schrift vorgelegt, die es aber in sich hat. Der Untertitel des in der „Collection Épures“ bei PUR erschienenen Büchleins zeigt das bereits an: Cabanel möchte die „histoire d’une hypocrisie sociale“, also die Geschichte einer sozialen Heuchelei, schreiben
Targeting non-small cell lung cancer with chimeric antigen receptor-engineered natural killer cells
Get PDFImmunotherapy has emerged as a transformative approach in the treatment of cancer, recruiting the body's immune system to target and eliminate malignant cells. However, the heterogeneity of solid tumors presents a significant challenge to the efficacy of these therapies. Tumor heterogeneity refers to the genetic, phenotypic, and microenvironmental variations within and between tumors, which can affect responses to immunotherapeutic agents. This complexity necessitates a personalized approach, as the immune landscape of each tumor influences the effectiveness of immune checkpoint inhibitors, chimeric antigen receptor (CAR)-based cell therapies, and other immunomodulatory strategies. Addressing tumor heterogeneity is crucial for optimizing immunotherapy outcomes, requiring profiling of tumor characteristics. Tumors can also evolve under selective pressures imposed by the immune system and therapeutic interventions, leading to the emergence of resistant clones.
In previous work by our group, an ErbB2 (HER2)-specific CAR was generated and transduced into clinically usable NK-92 cells (NK-92/5.28.z). The NK-92 cells carrying this second-generation CAR with CD28 and CD3ζ signaling domains demonstrated increased anti-tumor activity against various malignancies in preclinical studies. In addition, it was shown in immunocompetent mouse models that ErbB2-specific NK-92 cells can induce an endogenous immune response against tumor cells. These results led to the initiation of a clinical trial (CAR2Brain) in which the safety and efficacy of this cellular immunotherapy in patients with recurrent ErbB2-positive glioblastoma are currently being investigated. Since ErbB2 also plays a significant role in other tumor entities, including non-small cell lung cancer (NSCLC), an important goal of this work was to investigate the antitumor activity of CAR-NK cells against ErbB2-positive lung cancer cells. These investigations are a prerequisite for the potential future clinical use of NK-92/5.28.z cells for the treatment of patients with lung cancer. In flow cytometry-based and luciferase-based assays, ErbB2-specific NK-92/5.28.z cells indeed displayed high and specific cytotoxicity against both, the human lung cancer cell lines A549 and Calu-3 that naturally express elevated ErbB2 levels, and the ErbB2-transduced murine lung cancer cell line LC6/ErbB2.
As tumor heterogeneity poses a barrier to antigen-based therapy, another important goal of this work was to examine the use of a dual-CAR approach for the treatment of solid malignancies. This was investigated using two different strategies. Firstly, PD-L1-specific CARs were designed and transduced into NKL, NK-92 and NK-92/5.28.z cells. PD-L1 was chosen as an appropriate target as it serves as an important mechanism in tumor immune evasion. Moreover, PD-L1 directed therapies, notably immune checkpoint inhibitors, have been shown to have a significant effect on the clinical outcome of numerous malignancies, including non-small cell lung cancer. In a second approach, an NKG2D-based CAR (NKAR), previously developed in our laboratory, was transduced as a second receptor into ErbB2-specific NK-92/5.28.z CAR-NK cells. NKG2D-ligands (NKG2D-L), encompassing the MIC and ULBP protein families, are upregulated on transformed cells and play an important role in tumor immune surveillance. Due to their almost complete absence from healthy cells, they are regarded as a potential universal target for antigen-based therapy. Dual-CAR NK cells co-expressing the ErbB2-specific CAR together with a PD-L1-specific (NK-92/5.28.z/PD-L1) or the NKG2D-L-specific NKAR molecule (NKAR-NK-92/5.28.z) had a similar viability and proliferation rate as NK-92/5.28.z cells. Likewise, the natural cytotoxicity of dual-CAR cells, as measured against K562 cells, was not different from that of single-CAR NK cells. This is important, since intrinsic natural cytotoxicity can contribute to the overall response of CAR-NK cells against malignant cells.
Detailed analysis of PD-L1 as a target antigen in this study showed that unlike the constitutive expression of ErbB2, the expression of PD-L1 is induced by NK-92 cells, and to a larger extent by activated NK-92 cells. As results of transwell assays show, this induction does not require physical contact between effector and target cells, but is mediated by cytokines such as IFN-γ. This underscores the importance of PD-L1 as a target for CAR therapy. As neighboring NK-92 cells induce its expression, cancer cells that initially do not express PD-L1 or are low expressors upregulate it on their cell surface, thus exposing themselves as targets of PD-L1-CAR expressing NK cells.
Cytotoxicity assays with lentivirally transduced NK cells demonstrated the activity of PD-L1-CARs when expressed as a single-CAR, and their contribution to the lysis of dual-target tumor cells when expressed concurrently with the ErbB2-specific CAR. Thereby, NKL, parental NK-92 and NK-92/5.28 cells expressing either a first-generation (PD-L1.z) or a second-generation (PD-L1.28.z) CAR specifically and efficiently lysed PD-L1-positive target cells. However, expression of a PD-L1.TM CAR, which lacks intracellular signaling domains, only activated NK-92 and NK-92/5.28.z cells against PD-L1-positive targets, but not NKL cells. Though the reason for this difference was not investigated further, it appears likely that the CD28 transmembrane domain still present in the PD-L1.TM CAR could mediate dimerization with endogenous CD28 that is only expressed in NK-92 cells but not in NKL cells, thereby acting as a target-specific costimulatory receptor. When dual-CAR NK-92 cells co-expressing ErbB2- and PD-L1-specific CARs were tested, each CAR was shown to work independently, thus serving as a possible solution to heterogeneous antigen presentation and to tumor immune evasion through antigen downregulation. Moreover, in the case of lung cancer cells, simultaneous targeting of PD-L1 and ErbB2 led to a higher specific lysis than achieved with NK-92/5.28.z cells that only recognize ErbB2. Accordingly, in degranulation assays dual-CAR NK-92 cells displayed a higher level of CD107a expression after incubation with ErbB2 and PD-L1 double-positive A549 cells compared to parental A549 cell expressing only ErbB2. When a mixed population of target cells, expressing one or both target antigens, was co-cultured with either dual-CAR NK-92 cells or a combination of two single-CAR (ErbB2- or PD-L1-specific) NK-92 variants, no difference in specific lysis was found, indicating that in this case both approaches for dual-targeting were effective.
NKAR-NK-92/5.28.z cells, generated in this work by lentiviral transduction of ErbB2-specific NK-92/5.28.z cells with a vector encoding an NKG2D-L-specific NKG2D.z CAR (NKAR), were tested in similar experiments. Unlike parental NK-92/5.28.z cells, the dual-CAR NK cells mediated effective lysis of MDA-MB468 cells, a human breast cancer cell line that is ErbB2-negative but NKG2D-L-positive. NKAR-expressing cells were further tested in combination with bispecific antibodies (NKAB molecules) that recognize NKG2D via a single-chain fragment variable (scFv) domain derived from NKG2D-specific antibody Kyk2.0. For tumor targeting, these NKAB molecules contain a second scFv domain either derived from the clinically used antibody cetuximab which recognizes the tumor-associated antigen EGFR (NKAB-EGFR), or atezolizumab which binds to PD-L1 (NKAB-PDL1). As a model, murine glioblastoma cells (GL261) were previously modified by our group to ectopically express either EGFR (GL261/EGFR), ErbB2 and EGFR (GL261/ErbB2/EGFR), or PD-L1 (GL261/PD-L1). As GL261 is a murine cell line, the human NKAR does not recognize murine NKG2D-Ls it might express, ensuring that any response is NKAB-induced. NKAB-EGFR successfully mediated the lysis of EGFR-positive GL261 cells by NKAR-expressing NK-92 cells, while not contributing significantly to the lysis of double-positive GL261/ErbB2/EGFR cells by NKAR-NK-92/5.28.z cells. However, when ErbB2-mediated activity was inhibited with a blocking antibody, imitating downregulation of ErbB2 on the target cells, NKAB-EGFR-mediated activation of the NKAR compensated in dual-CAR NK cells for the loss of ErbB2-CAR activity. Results from these assays also showed that as in the case of PD-L1-CARs, NKAR and ErbB2-CAR activities are independent of each other. Similar experiments conducted with A549 and Calu-3 lung cancer cells revealed that for these targets co-incubation with NKAR-NK-92/5.28.z cells and NKAB-EGFR did not lead to improved cytotoxicity. This may be attributed to the relatively low expression of EGFR by these cell lines, since NKAB-EGFR did also not restore cytotoxicity when ErbB2-mediated killing was blocked.
The ability of NKAB-PDL1 to activate NK-92 cell via the NKAR receptor was tested in a similar fashion, demonstrating its ability to mediate cytotoxicity against PD-L1-positive target cells. When co-cultured with MDA-MB468/PD-L1 cells, it further enhanced the cytotoxicity mediated by the NKAR alone through interaction with NKG2D-Ls. Importantly, the presence of NKAB-PDL1 did not inhibit lysis of NKG2D-L-positive but PD-L1-negative target cells by NKAR-expressing NK cells. As opposed to the results obtained with NKAB-EGFR, the addition of NKAB-PDL1 fully restored specific lysis of ErbB2 and PD-L1 double-positive A549 and Calu-3 cells when ErbB2-mediated killing was inhibited, which can be attributed to the much higher level of PD-L1 in the target cells when compared to EGFR.
Subsequently, both NKAB molecules were tested in combination using GL261/EGFR and GL261/PD-L1 cells as targets. Firstly, each target cell line was co-incubated with NKAR-NK-92/5.28.z cells with either NKAB-EGFR or NKAB-PDL1, or both molecules. Thereby, only the relevant NKAB molecule mediated specific lysis. When these assays were repeated with a mixed population of GL261/EGFR and GL261/PD-L1 cells, the use of both NKAB molecules significantly increased cell killing compared to the addition of either NKAB alone, but with each NKAB molecule only mediating lysis of the respective target cell population in the mixture.
The data obtained in this work contribute to our general understanding of the function of single-CAR and dual-CAR NK cells, and may support the development of novel cellular immunotherapies for lung cancer. As a next step, the specific activity of ErbB2-CAR NK cells against ErbB2-positive lung cancer cells shown in this study in in vitro models should be further investigated in a suitable mouse tumor model in vivo. Furthermore, as demonstrated in this work, dual-CAR NK cells either targeting ErbB2 and PD-L1, or ErbB2 and a second antigen through the NKAB-NKAR system, mediate enhanced cell lysis against double-positive target cells, but with either CAR also working independently against target cells that express only one antigen. This demonstrates a therapeutic benefit for dual-CAR use, which could be employed to address the clinical problem of tumor cell heterogeneity with rationally designed bi-functional CAR effector cells
Comparison of the Performance of State-of-the-Art Photoconductive Receivers for Terahertz Photonic Spectrum Analysers
Get PDFWith the increased interest in Terahertz applications and technologies there is a growing demand of new and improved transmitters. Spectrum analyzers are frequently used to characterise the spectral purity of transmitters. The Terahertz range state-of-the-art electronic spectrum analyzers are limited in terms of frequency coverage and are very expensive. In this article we present an alternative: photonic spectrum analysers based on the optical downconversion of continuous-wave lasers and photoconductive receivers. We compare the performance of two state-of-the-art photoconductive receivers in terms of their spectral roll-off and the displayed average noise level. We conclude with a comparison of the displayed average noise level of the photonic spectrum analyser to that of an electronic system employing extender modules
Die DNA-Doppelstrangbruch-Reparatur nach Exposition niedriger Dosen Röntgenstrahlung
Get PDFNiedrige Dosen ionisierender Strahlung im Bereich von wenigen mGy bzw. mSv sind im Leben eines jeden Menschen allgegenwärtig. Im Schnitt ist ein Mensch in Deutschland jährlich einer Dosis von etwa 4 mSv ausgesetzt, welche sich aus der natürlichen Strahlenexposition, z.B. durch das Vorkommen von Radionukliden in Böden oder manchen Lebensmitteln, und der Strahlenexposition durch u.a. CT-Aufnahmen im Rahmen von medizinischen Untersuchungen oder anderen technischen Anwendungen von ionisierender Strahlung zusammensetzt. Selbst solche niedrigen Dosen können die Zelle schädigen. Dabei sind insbesondere DNA-Doppelstrangbrüche (DSBs) kritisch, da sie die genetische Integrität der Zellen gefährden können, was die Entstehung von Krebs begünstigen kann. Zellen haben daher eine Vielzahl an Mechanismen entwickelt, um auftretende DSBs zu reparieren. Dennoch werden DSBs, die durch niedrige, alltäglich relevante Dosen ionisierender Strahlung verursacht werden, in normalen humanen Fibroblasten überraschenderweise nur ineffizient repariert. Im Gegensatz dazu werden DSBs, die durch hohe Strahlendosen verursacht werden, deutlich effizienter repariert. Wie die Zellen dosisabhängig die Reparatur von DSBs regulieren, ist bislang kaum bekannt und Gegenstand der Untersuchungen dieser Arbeit.
Um die ineffiziente Reparatur nach niedrigen Dosen und den zugrundeliegenden Mechanismus zu charakterisieren, wurde in dieser Arbeit zunächst in experimentellen Studien in kultivierten, humanen Fibroblasten und Epithelzellen bestätigt, was aus früheren Untersuchungen mit Fibroblasten (Rothkamm & Löbrich, 2003 und Grudzenski et al., 2010) bekannt war. So wurde in dieser Arbeit erneut gezeigt, dass Zellen in der G0/G1-Phase entstandene DSBs nach einer Bestrahlung mit hohen Dosen Röntgenstrahlung (z.B. 1 Gy) effizient reparieren, während sie DSBs nach Bestrahlung mit niedrigen Dosen (z.B. 10 mGy) ineffizient reparieren, sodass selbst nach 24 h Reparaturzeit die meisten DSBs unrepariert verbleiben. Werden die Zellen zusätzlich zur Bestrahlung mit niedrigen Dosen mit geringen Mengen Wasserstoffperoxid behandelt, kann die Reparatureffizienz deutlich gesteigert werden. Das Wasserstoffperoxid erzeugt in der verwendeten Konzentration Radikale in der Zelle, ohne selbst DSBs zu verursachen. Darauf aufbauende neue Untersuchungen mit einer molekularen Sonde, deren Fluoreszenzintensität vom Radikallevel der Zelle abhängt, bestätigen, dass bei niedrigen Dosen Röntgenstrahlen tatsächlich kaum Radikale entstehen, während bei hohen Dosen bzw. der Kombination aus Wasserstoffperoxid-Behandlung und Bestrahlung mit niedrigen Dosen vergleichbare, deutlich höhere Radikallevel entstehen. Dieser Unterschied im Radikallevel könnte den Unterschied der Reparatureffizienz bei verschiedenen Dosen erklären. Die Relevanz von intrazellulären Radikalen bei der Regulation der DSB-Reparatureffizienz wurde in vergleichenden Studien der DSB-Reparatureffizienz nach Bestrahlung mit Röntgenstrahlen sowie Anwendung des Radiomimetikums Neocarzinostatin (NCS) bestätigt, das im Gegensatz zur Strahlung weniger und räumlich begrenzt Radikale generiert. DSBs, die durch NCS erzeugt wurden, wurden etwas schlechter repariert als DSBs, die durch eine vergleichbare Strahlendosis erzeugt wurden. Diese Ergebnisse zeigen, dass es ein kritisches Level von intrazellulären Radikalen gibt, welche für die Aktivierung der DSB-Reparatur nötig ist, was eine effiziente Reparatur der Brüche erlaubt.
Darauf aufbauend stellte sich die zentrale Frage dieser Arbeit, welche der involvierten DSB-Reparaturproteine radikalabhängig reguliert werden. Die DNA-abhängige Proteinkinase - catalytic subunit (DNA-PKcs) wurde als möglicher Kandidat identifiziert. Zum einen spielt DNA-PKcs eine zentrale Rolle in der DSB-Reparatur in Zellen der G0/G1-Phase, spezifisch im DSB-Reparaturweg Non-homologous end joining (NHEJ), sodass es plausibel erscheint, dass ein inaktives NHEJ für eine eingeschränkte DSB-Reparatur verantwortlich ist. Tatsächlich gab es im Rahmen dieser Arbeit experimentelle Hinweise darauf, dass NHEJ nach niedrigen Strahlendosen nicht aktiv sein könnte, aber durch Wasserstoffperoxid stimuliert wird. Zum anderen ist für die mit DNA-PKcs eng verwandte Kinase Ataxia Telangiectasia Mutated (ATM) eine radikalvermittelte Aktivierung beschrieben (Guo et al., 2010). Um zu analysieren, wie hoch die jeweilige Aktivität von DNA-PKcs und ATM bei verschiedenen Strahlendosen ist, wurde ihre Fähigkeit, die Histonvariante H2AX schadensspezifisch zu phosphorylieren, ausgenutzt. So wurde gezeigt, dass DNA-PKcs durch eine niedrige Strahlendosis – im Gegensatz zu einer hohen Dosis – nicht aktiviert wird, ATM dagegen dosisunabhängig aktiviert wird. Damit liefert diese Arbeit erste Hinweise auf einen radikalvermittelten Aktivierungsweg von DNA-PKcs, der bei niedrigen Radikalleveln nicht ausreichend stimuliert wird.
Daraufhin wurde die radikalvermittelte Aktivierung von DNA-PKcs näher untersucht. Es wurde die Hypothese untersucht, dass die Aktivität von DNA-PKcs durch Proteine gesteuert wird, die wiederum selbst auf das zelluläre Radikallevel reagieren. Peroxiredoxine wurden in den letzten Jahren als redoxabhängige Regulatoren der zellulären Schadensantwort beschrieben und wurden daher auch in dieser Arbeit hinsichtlich ihrer Rolle in der DSB-Reparatur untersucht. Durch den Inhibitor Adenanthin, welcher thiolhaltige Proteine und hier insbesondere die Peroxiredoxine PRDX2 und PRDX1 inhibiert, sowie durch die Depletion von PRDX2 und PRDX1 mittels siRNA, wird die Reparatureffizienz und DNA-PKcs-Aktivität bei niedrigen Dosen gesteigert, ohne dass das Radikallevel erhöht wird. Dies deutet auf eine kritische Rolle von Peroxiredoxinen in der Regulation der DNA-PKcs-Aktivität und damit der DSB-Reparatureffizienz hin. Co-Immunopräzipitationsstudien mit Flag-getaggtem PRDX2 in HEK293T-Zellen legen nahe, dass DNA-PKcs und PRDX2 bzw. möglicherweise auch andere Peroxiredoxine, wie PRDX1, bei niedrigen Dosen miteinander interagieren, bei höheren Dosen bzw. Radikalleveln dagegen nicht. Somit konnten in dieser Arbeit erste Hinweise erlangt werden, dass es eine radikalabhängige Interaktion zwischen PRDX2 bzw. PRDX1 und dem NHEJ-Faktor DNA-PKcs gibt. Diese Ergebnisse geben Anlass zur Vermutung, dass durch diese Interaktion die Aktivität von DNA-PKcs bei niedrigen Dosen gehemmt wird, was für die verminderte DNA-PKcs-Aktivität und die ineffiziente Reparatur nach niedrigen Dosen mitverantwortlich ist.
Diese Arbeit trägt dazu bei, die ablaufenden zellulären Prozesse nach einer Exposition mit niedrigen, alltäglichen Strahlendosen mechanistisch besser zu charakterisieren. So konnte einerseits eine neuartige radikalabhängige Aktivierung von DNA-PKcs, sowie andererseits die Rolle der Peroxiredoxine in der DSB-Reparatur nach niedrigen Strahlendosen identifiziert werden. Dies hilft beim Verständnis, wie in Zellen radikal- bzw. dosisabhängig die Effizienz von DSB-Reparaturprozessen gesteuert werden. Diese Erkenntnisse zu den molekularen Mechanismen, die nach der Exposition mit niedrigen, alltäglichen Strahlendosen ablaufen, können langfristig helfen, die Wirkung und assoziieren Risiken solcher Expositionen zukünftig besser abschätzen zu können
Influence of reinforcement and its omission on trial‐by‐trial changes of response bias in perceptual decision making
Get PDFDiscrimination performance in perceptual choice tasks is known to reflect both sensory discriminability and nonsensory response bias. In the framework of signal detection theory, these aspects of discrimination performance are quantified through separate measures, sensitivity ( d′ ) for sensory discriminability and decision criterion ( c ) for response bias. However, it is unknown how response bias (i.e., criterion) changes at the single‐trial level as a consequence of reinforcement history. We subjected rats to a two‐stimulus two‐response conditional discrimination task with auditory stimuli and induced response bias through unequal reinforcement probabilities for the two responses. We compared three signal‐detection‐theory‐based criterion learning models with respect to their ability to fit experimentally observed fluctuations of response bias on a trial‐by‐trial level. These models shift the criterion by a fixed step (1) after each reinforced response or (2) after each nonreinforced response or (3) after both. We find that all three models fail to capture essential aspects of the data. Prompted by the observation that steady‐state criterion values conformed well to a behavioral model of signal detection based on the generalized matching law, we constructed a trial‐based version of this model and find that it provides a superior account of response bias fluctuations under changing reinforcement contingencies
RenalViz: Visual analysis of cohorts with chronic kidney disease
Get PDFChronic Kidney Disease (CKD) is a prominent health problem. Progressive CKD leads to impaired kidney function with decreased ability to filter the patients’ blood, concluding in multiple complications, like heart disease and ultimately death from the disease. In previous work, we developed a prototype to support nephrologists in gaining an overview of their CKD patients. The prototype visualizes the patients in cohorts according to their pairwise similarity. The user can interactively modify the similarity by changing the underlying weights of the included features. The work in this paper expands upon this previous work by the enlargement of the data set and the user interface of the application. With a focus on the distinction between individual CKD classes we introduce a color scheme used throughout all visualization. Furthermore, the visualizations were adopted to display the data of several patients at once. This also involved the option to align the visualizations to sentinel points, such as the onset of a particular CKD stage, in order to quantify the progression of all selected patients in relation to this event. The prototype was developed in response to the identified potential for improvement of the earlier application. An additional user study concerning the intuitiveness and usability confirms good results for the prototype and leads to the assessment of an easy-to-use approach
The Development of Ecological Identities in Children’s Books: A Linguistic Approach to Character Positioning as Eco-Rebels
Get PDFEco-rebels can provide readers a role model that encourages sustainable thinking and action in everyday life. The protagonists in ecological children’s and young adult literature (CYL) are mostly ignorant at the beginning. They learn as the story progresses and develop into environmentally conscious individuals who are taken seriously and actively committed to protecting their environment. This article would like to present a linguistic method for analyzing how readers are guided in ecological CYL, allowing them to follow and understand the protagonist’s change towards becoming an eco-rebel. This study hypothesizes that the development of an ecological identity, although an individual evolution in the story, is a pattern of ecological CYL. The possibilities for identification that a text offers its reader must be considered as crucial for the experiences gained within the fiction framework to influence real consciousness and development processes. In this context, Bamberg’s identity dilemmatic spaces are used for the analysis, allowing the construction of identity in storytelling to be made tangible. These identity dilemmatic spaces have been expanded to include linguistic categories. The construction of the figure of the eco-rebel can thus be analyzed according to different linguistically based or narrative-based aspects like speech markings or the development of an agenda