Technische Universität Dresden: Qucosa
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Spatial patterning of mitochondrial metabolism during early vertebrate development
No full textLike all living systems, developing embryos use metabolic pathways to convert energy and to build cellular structure. Upon fertilization, embryos undergo a series of cleavage divisions followed by the maternal zygotic transition prior to gastrulation. During cleavage divisions, cells divide rapidly without growth in volume in most animal species.
Global metabolic measurements including oxygen consumption and heat dissipation rate measurements during cleavage development in different species have shown that the overall energy expenditure increases despite the absence of growth. This raises the question of how embryonic metabolism satisfies the increasing energy demands.
Mitochondrial metabolism is essential for providing ATP, the most fundamental energy currency of cells. A large pool of fragmented and immature mitochondria is maternally deposited into the oocyte, where they remain in a quiescent state until fertilization. During cleavage, mitochondrial content in terms of numbers remains constant and mitochondria are equally distributed between blastomeres to ensure proper development in most species. Thus, while the embryo’s energy demand increases, its mitochondrial content remains constant, leading to the central question of this thesis: How is mitochondrial activity regulated in time and space to meet the increase in energy demands of early cleavage development?
In this thesis, we address this question by analyzing mitochondrial activity, function and morphology in zebrafish cleavage stage embryos using live imaging, electron microscopy and a theoretical modeling approach, combined with heat dissipation and oxygen consumption measurements. We have established a live imaging approach and image analysis pipeline to visualize and quantify mitochondrial activity and NADH fluorescence lifetime in early zebrafish embryos We found a striking spatial pattern of mitochondrial activity with high activity at the cell periphery gradually decreasing towards the cell center, while mitochondrial distribution is rather homogenous. This suggests that mitochondria are activated from the cell surface. As the increase in energy expenditure increases proportional to the increase in surface area, mitochondrial activation from the plasma membrane might be the underlying mechanism to gradually increase ATP supply to meet the embryo’s energy demand.
By further characterizing the mitochondrial activity gradient we found that the fraction of active mitochondria lies in a range of ~ 20 ± 5 µm from the plasma membrane during early cleavage stages, independent of the stage and cell size. Using a theoretical model, we showed that the gradient fits a diffusion-degradation model, suggesting that a molecular reaction-diffusion mechanism may regulate mitochondrial activation. Analyzing mitochondrial activity in embryos of other species revealed that mitochondrial activation from the cell periphery occurs beyond zebrafish, except in mouse embryos, indicating species-specific and cell size-dependent differences. To further explore the relationship between mitochondrial activity and structure, we analyzed mitochondrial morphology using electron microscopy in zebrafish embryos. These data revealed that mitochondria remain round and fragmented throughout cleavage divisions and contain large cristae structures. We found that mitochondrial area is larger close to the plasma membrane where mitochondria display increased activity and the overall size increases over time suggesting that mitochondria undergo size maturation. Analyzing potential mechanisms upstream of mitochondrial activation, we found that Ca²⁺ waves are required to induce activity. Live imaging using genetically encoded Ca²⁺ sensors revealed that dynamic Ca²⁺ waves originating from the cleavage furrow precede mitochondrial activation. Pharmacological inhibition of Ca²⁺ release and uptake from the ER disrupted mitochondrial activation, indicating that Ca²⁺ signaling is necessary for initiating mitochondrial activity. In the last part, we explored potential non-energetic functions of mitochondria during cleavage-stage development, particularly their involvement in regulating zygotic genome activation (ZGA). We observed that active mitochondria begin to form transient contacts with the nucleus at later cleavage stages, just prior to the onset of ZGA. These findings suggest that mitochondrial-nuclear interactions may facilitate the transfer of metabolites, signaling molecules, or metabolic enzymes needed for transcriptional activation in zebrafish embryos.
Overall, this thesis reveals that mitochondrial metabolism in early embryos is spatially and temporally organized within the large embryonic cells. The gradual activation of mitochondria from the plasma membrane might serve as a mechanism to meet the increasing energetic demands of early development. More broadly, our results might help to further understand how mitochondrial metabolism transitions from a quiescent state to an activated state. This work contributes to a deeper understanding of how mitochondria organize and distribute bioenergetic and regulatory tasks within the subcellular environment and demonstrates their crucial role in early embryonic development
Binary and ternary metal alloys as diffusion barriers in advanced copper interconnects.
No full textDie fortschreitende Miniaturisierung und Verdichtung von Mikrochips stellt eine Herausforderung für die Halbleiterindustrie dar. Dies betrifft auch die Kupfer-(Cu)-Metallisierungsschichten, die den elektrischen Signaltransport zwischen den Transistoren ermöglichen. Die derzeit gebräuchliche Diffusionsbarriere, bestehend aus einer TaN/Ta-Doppelschicht, verhindert effektiv die Diffusion von Cu in die umliegenden Isolationsschichten, trägt jedoch signifikant zum Gesamtwiderstand schrumpfender Cu-Leitungen bei. Daher wird nach alternativen Lösungen gesucht.
In den letzten 20 Jahren wurden zahlreiche Materialklassen als mögliche Diffusionsbarrieren vorgeschlagen, doch keine davon konnte sich bisher in der Halbleiterindustrie etablieren. Eine dieser Materialklassen sind Metalllegierungen. Obwohl viele Studien binäre Metalllegierungen als Cu-Diffusionsbarrieren untersucht haben, fehlt bislang ein systematischer Ansatz, der sowohl einen direkten Vergleich mit TaN als auch zwischen den verschiedenen Metalllegierungen ermöglicht.
In dieser Arbeit wird eine umfassende Analyse durchgeführt, um die Diffusionsbarrierefähigkeit binärer und ternärer Metalllegierungen zu bewerten. Mithilfe des Miedema-Modells wird die Morphologie der Legierungen in Abhängigkeit von ihrer Zusammensetzung vorhergesagt. Es wird gezeigt, dass dieses Modell auch für ultradünne Metalllegierungen mit Dicken von nur 15nm zuverlässig angewendet werden kann. Basierend auf den kombinierten Modell und experimentellen Ergebnissen werden ausgewählte Metalllegierungen hinsichtlich ihrer
Diffusionsbarrierefähigkeit bewertet. Dabei kommt die Röntgenphotoelektronenspektroskopie-Tiefenprofilierung zum Einsatz. Diese Methode, die bisher kaum zur Bewertung von Diffusionsbarrieren in Interconnects verwendet wurde, liefert neue Erkenntnisse über die Diffusionsmechanismen von Cu in den Legierungen. Es zeigt sich, dass die Morphologie einen entscheidenden Einfluss auf die Barrierefähigkeit hat, wobei eine gut definierte Mikrostruktur
sowohl für die Barrierewirkung als auch für einen niedrigen elektrischen Widerstand von Vorteil ist. Die Quantifizierung der Cu-Diffusion in ausgewählten Metalllegierungen wird durch den Einsatz des Mixing-Roughness-Information-Depth-(MRI)-Modells demonstriert. Eine Erweiterung des Modells, die präferentielles Sputtern berücksichtigt, ermöglicht dessen Anwendung auf Legierung/Cu Diffusionsprofile. Mit dem in dieser Arbeit entwickelten Analyseansatz werden binäre und ternäre Metalllegierungen mit herausragender Cu-Diffusionsbarrierefähigkeit identifiziert. Zur Bewertung ihrer möglichen Integration in Interconnects werden Haftungstests mithilfe des Modified Edge Lift-Off Test (MELT) durchgeführt. Abschließend werden die bei der Legierungsherstellung verwendeten Metalle hinsichtlich ihrer Versorgungsrisiken und der Umweltauswirkungen durch Abbau und Raffinierung analysiert.The semiconductor industry faces significant challenges due to the ongoing miniaturization and densification of microchips. These advancements also impact the copper (Cu) metallization layers, which enable electrical signal transport between the transistors. The commonly used diffusion barrier bi-layer TaN/Ta, prevents Cu diffusion into the surrounding insulating layers, but increases the overall resistance of shrinking Cu lines. This necessitates the search for alternatives. Over the last 20 years, various material classes have been proposed as alternative diffusion barriers, but none have been adopted by the semiconductor industry. One such material class is metal alloys. While many publications have proposed binary metal alloys as Cu diffusion barriers, a systematic approach comparing their performance to TaN
and among the metal alloys themselves is still lacking.
To address this gap, this work presents a detailed analysis evaluating the diffusion barrier performance of binary and also ternary metal alloys. Using the Miedema model, predictions of the morphology depending on the alloy compositions are provided. It is demonstrated that the model is an effective tool, even for ultra-thin metal alloys with thicknesses as small as 15 nm. Based on combined model predictions and experimental results, selected metal alloys are evaluated with regard to their diffusion barrier performance. X-ray photoelectron spectroscopy (XPS) depth profiling, a method rarely used for evaluating diffusion barriers in interconnects, is applied. This approach offers new insights into the diffusion mechanisms of Cu into the alloys. Morphology is shown to substantially affect barrier performance, with
a well-defined microstructure proving beneficial for both diffusion blocking and electrical resistivity. Quantification of Cu diffusion in selected metal alloys is achieved using the mixing-roughnessinformation depth (MRI) model. An extension of the model, which accounts for preferential sputtering, is introduced, enabling its application to alloy/Cu diffusion profiles. With this comprehensive analysis, binary and ternary metal alloys demonstrating excellent Cu diffusion barrier performance are identified. To evaluate their potential for integration into interconnects, adhesion tests are conducted using a modified edge lift-off test (MELT). Additionally, the metals used in alloy fabrication are assessed for supply risks and environmental impact, considering factors such as mining and refining
Physical Principles and Effects of Fluorescence Tracers in the Circular Economy of Plastics
No full textIn the context of the rising volume of plastic waste, the increasing requirements for recycling quotas and targets, and the ecological impact of the production and disposal of plastic products, there is a growing interest in the development of innovative identification and sorting technologies for polymers. One such technology is the incorporation of fluorescent tracer additives into the plastic during the manufacturing process, which acts as an independent sorting criterion in material identification. Furthermore, the tracers and the unique fluorescence pattern, which is randomly generated during the production process, can be detected and subsequently assigned to an individual product as a unique identifier. This doctoral thesis analyzes the physical effects of tracers in the polymer recycling for both applications, material and product identification. This thesis addresses five research questions to investigate and analyze these relationships.
Research question 1 (Which quality problems recycling compounders are encountered in practice, where they occur, and which mitigation options might be reasonable?) analyzes the occurrence of typical quality problems in compounding. Compounding is the final step in material recycling and the first step before the material is reprocessed into a new product. To this end, a comprehensive literature review and a survey of 20 compounding companies in Germany were carried out. The companies were asked by questionnaire about the processes and materials used, the quality problems, and the measures taken to reduce them. Quality problems were found to be primarily caused by impurities and contamination in the input material stream. The frequency of quality problems is independent of the type of input stream (pre-sorted vs. mixed, post-industrial vs. post-consumer) or if in-house sorting of the input is conducted. However, the participating companies indicated that knowledge of the detailed composition of the input material stream could contribute to reducing quality problems.
Research question 2 (What effects do fluorescent tracer additives have on the material properties of polymers in the compounding and recycling process?) investigates the influence of up-conversion fluorescence tracers on the material properties of polymers under multiple processing. For this purpose, multiple processing by extrusion of PET was simulated and the thermal, mechanical, chemical, rheological, and optical material properties were recorded. A total of up to six extrusion cycles were carried out with four different tracer concentrations, ranging from 0 ppm to 1000 ppm. The results of the study show that the tracer does not influence the degradation processes in PET. The results show the thermo-mechanical degradation processes characteristic of PET, such as chain shortening, a reduction in molecular weight, and the formation of new functional groups.
Research question 3 (To what extent does the fluorescence signal of tracer additives remain stable and measurable after multiple recycling cycles?) supplements the investigation scope of the PET samples regarding the detection capability of the fluorescence tracers after multiple processing. The measurements of the up-conversion photoluminescence showed that the fluorescence signal is still detectable and suitable for use in material identification. The tracers exhibit a high degree of stability when subjected to the thermal and mechanical influences associated with polymer processing. A slight change in the fluorescence intensity is attributable to the reduced optical properties in transparency and color (yellowing).
Research question 4 (How do the size and distribution of tracer particles influence their fluorescence within a polymer matrix?) focuses on the use case of product identification, which is based on the fluorescence pattern of the individual particles. This question investigates the influence of particle size and spatial arrangement on the fluorescence in the polymer. The literature shows that the particle shape, particle size, and chemical composition significantly influence the fluorescence intensity of the particle. In addition, the fluorescence intensity and area are experimentally investigated depending on the depth position of the particle in the polymer matrix. Therefore, highly transparent PMMA was used as the model material, into which five different particle size distributions were incorporated during processing. It was found that larger particles exhibit a stronger fluorescence than smaller ones and are also detectable when they are embedded deeper in the polymer matrix. If the particles are positioned too deeply in the polymer matrix, differentiation from the background fluorescence is no longer possible.
The concluding research question 5 (How can the actual particle size distribution of tracer additives in polymers be determined from the fluorescence patterns?) uses the sample materials from research question 4 and investigates whether it is possible to determine the particle size distributions based on the optical measurement of the fluorescent area. Additionally, it is tested whether the particle size distributions can be distinguished from one another. For this purpose, images of the samples are taken and the fluorescence areas are computer-aided analyzed according to their size. The analysis of the four characteristics, particle number, fluorescence intensity, and D50 and D95 of the fluorescence area distribution, enables a significant differentiation of the five particle size distributions. Furthermore, it is possible to determine a transformation curve for each particle size distribution by smoothing the distribution function using a logistic curve and comparing it with the actual particle distribution function. The determined transformation curve enables an approximation of the particle size distribution to be determined based on the measured fluorescence area distribution. The transferability of this procedure was successfully evaluated on PET.
This thesis examines the material compatibility of tracers and polymers and describes the physical effects that are relevant for material and product identification. From a technical perspective, the investigations of tracers show promising results to improve sorting and consequently to obtain higher quality recyclates. In addition, the investigations should be extended to other material groups. The complex chemical structure of both the polymers and the tracers can cause other physical interaction effects to occur. It must be noted that the use of tracers entails the risk of tracer carry-over and consequently new contamination of the material flows. Other innovative identification technologies, such as digital watermarks or image recognition, do not face this issue. At present, tracer technology, digital watermarks, and image recognition are still under development. Therefore, those technologies lack field-proven circular economy figures on costs, throughput, and sorting purity. Nevertheless, these technologies can help to promote the provision of higher-quality recyclates and thus support the conservation of finite resources and environmental protection.:1 Introduction
1.1 Motivation and Scope
1.2 Research Questions
2 Quality Challenges in Compounding
3 Influence of Tracer Additives on Polymer Properties
4 Fluorescence Signal Stability during Recycling
5 Factors Affecting the Tracer Fluorescence
6 Deriving Particle Size Distribution from Fluorescence Patterns
7 Discussion and Outlook
7.1 Synthesis of Research Results
7.2 Limitations
7.3 Outlook and Future Research
8 References
9 Annex: Full-Text Articles
9.1 Quality Aspects in the Compounding of Plastic Recyclate
9.2 Effects of Fluorescent Tracer Additives on PET During Material Recycling
9.3 Particle Size Distribution and Fluorescence Patterns of Tracer Additives in PolymersIm Kontext des steigenden Kunststoffabfallaufkommens, der zunehmenden Anforderungen an Recyclingquoten und -ziele sowie der ökologischen Belastung durch die Produktion und Entsorgung von Kunststoffprodukten wird derzeit eine Vielzahl innovativer Identifikationstechnologien und Sortiertechnologien für Kunststoffe erforscht. Eine dieser Technologien ist die Tracer-Technologie, bei der ein fluoreszierendes Tracer-Additiv bereits während des Herstellungsprozesses in den Kunststoff eingearbeitet wird und in der Materialidentifikation als werkstoffunabhängiges Sortierkriterium dient. Darüber hinaus können die Tracer und das einzigartige Fluoreszenzmuster, welches zufällig bei der Produktion entsteht, erfasst und als eindeutige Identifikation einem einzelnen Produkt zugeordnet werden. In diesem Kontext analysiert die vorliegende Doktorarbeit die physikalischen Effekte von Tracern in der Kunststoff-Kreislaufführung für die beiden Anwendungsfälle Material- und Produktidentifikation. Die vorliegende Arbeit befasst sich mit fünf Forschungsfragen, welche darauf abzielen, diese Zusammenhänge zu untersuchen und zu analysieren.
Forschungsfrage 1 (Welche Qualitätsprobleme treten bei Recycling-Compoundern in der Praxis auf, wo entstehen sie und welche Maßnahmen könnten sinnvoll sein, um diese zu beheben?) analysiert das Auftreten typischer Qualitätsprobleme in der Compoundierung. Die Compoundierung stellt den finalen Schritt der Werkstoffwiederaufbereitung dar und den ersten, bevor das Material wieder zu einem neuen Produkt verarbeitet wird. Zu diesem Zweck wurde eine umfassende Literaturrecherche sowie eine Umfrage mit 20 Compoundier-Betrieben aus Deutschland durchgeführt. Die Unternehmen wurden mittels eines Fragebogens zu den von ihnen angewandten Verfahren, den verwendeten Materialien, den Qualitätsproblemen sowie den ergriffenen Maßnahmen zu deren Reduzierung befragt. Die Auswertung der Umfrageergebnisse ergab, dass Verunreinigungen und Kontaminationen im Eingangsstoffstrom als Hauptursache für Qualitätsprobleme identifiziert wurden. Die Häufigkeit von Qualitätsproblemen ist unabhängig von der Art der Inputströme (sortenrein/gemischt, post-industrial/post-consumer) sowie davon, ob eine weitere Inhouse-Sortierung stattfindet. Die teilnehmenden Unternehmen gaben jedoch an, dass das Wissen über die detaillierte Zusammensetzung des Eingangsstoffstroms einen Beitrag zur Reduzierung von Qualitätsproblemen leisten könnte.
Forschungsfrage 2 (Welche Auswirkungen haben fluoreszierende Tracer-Additive auf die Materialeigenschaften von Polymeren im Compounding- und Recyclingprozess?) untersucht den Einfluss von Up-Conversion-Fluoreszenz-Tracern auf die Materialeigenschaften von Kunststoffen unter mehrfacher Verarbeitung. Zu diesem Zweck wurde eine mehrfache Verarbeitung durch Extrusion bei PET simuliert und die thermischen, mechanischen, chemischen, rheologischen und optischen Materialeigenschaften untersucht. Insgesamt wurden bis zu sechs Extrusionsdurchläufe mit vier verschiedenen Tracerkonzentrationen durchgeführt, die von 0 ppm bis 1000 ppm reichten. Die Ergebnisse der Untersuchungen zeigen, dass der Tracer keinen Einfluss auf die Abbauprozesse in PET hat. Die vorliegenden Ergebnisse zeigen die für PET charakteristischen thermo-mechanischen Abbauprozesse, wie Kettenverkürzungen, eine Reduktion des Molekulargewichts sowie die Bildung neuer Funktioneller Gruppen.
Forschungsfrage 3 (Inwieweit bleibt das Fluoreszenzsignal von Tracer-Additiven nach mehreren Recyclingzyklen stabil und messbar?) dient der Ergänzung des Untersuchungsumfangs der PET-Proben um die Detektionsfähigkeit der Fluoreszenztracer nach mehrfacher Verarbeitung. Die Messungen der Up-Conversion-Photolumineszenz ergaben, dass das Fluoreszenzsignal weiterhin detektierbar ist und sich für den Einsatz zur Materialidentifikation eignet. Die Tracer zeichnen sich durch eine hohe Stabilität gegenüber den thermischen und mechanischen Einflüssen der Kunststoffaufbereitung aus. Eine leichte Veränderung der Fluoreszenzintensität ist auf die verschlechterten optischen Eigenschaften (Transparenz und Vergilbung) zurückzuführen.
Forschungsfrage 4 (Wie beeinflussen die Größe und Verteilung von Tracer-Partikeln deren Fluoreszenz innerhalb einer Polymermatrix?) fokussiert den Anwendungsfall der Produktidentifikation, der auf dem Muster einzelner Fluoreszenzpartikel basiert. Die vorliegende Untersuchung beschäftigt sich damit, wie Größe und räumliche Verteilung der Partikel die Fluoreszenz im Polymer beeinflusst. Die Literatur legt nahe, dass die Partikelform, die Partikelgröße sowie die chemische Zusammensetzung maßgeblich die Fluoreszenzintensität des Partikels beeinflussen. Darüber hinaus wurde die Tiefenposition des Partikels in der Polymermatrix in Abhängigkeit zur Größe und der Fluoreszenzintensität in dieser Forschungsfrage experimentell untersucht. Als Modellmaterial wurde hierfür hochtransparentes PMMA verwendet, in welches bereits im Herstellungsprozess fünf unterschiedliche Partikelgrößenverteilungen eingearbeitet wurden. Es konnte festgestellt werden, dass größere Partikel im Vergleich zu kleineren eine höhere Leuchtkraft aufweisen und dadurch, auch bei tieferer Einbettung in die Polymermatrix noch detektierbar sind. Bei einer zu tiefen Positionierung der Partikel in der Polymermatrix ist eine Differenzierung von der Hintergrundfluoreszenz nicht mehr möglich.
Die abschließende Forschungsfrage 5 (Wie kann die tatsächliche Partikelgrößen-verteilung von Tracer-Additiven in Polymeren anhand der Fluoreszenzmuster bestimmt werden?) bedient sich der Probenmaterialien aus Forschungsfrage 4 und untersucht, ob die Ermittlung der Partikelgrößenverteilungen mittels optischer Messung der Fluoreszenzflächen möglich ist und ob die Partikelgrößenverteilungen voneinander zu unterscheiden sind. Zu diesem Zweck werden Bildaufnahmen der Proben angefertigt und die Fluoreszenzflächen computergestützt nach ihrer Größe ausgewertet. Die Analyse der vier Charakteristika Partikelanzahl, Fluoreszenzintensität und D50 und D95 der Fluoreszenzflächenverteilung ermöglicht eine signifikante Unterscheidung der fünf Partikelgrößenverteilungen. Des Weiteren besteht die Möglichkeit, mittels einer Glättung der Verteilungsfunktion durch eine logistische Kurve und der Vergleich mit der tatsächlichen Verteilungsfunktion eine Transformationskurve je Partikelgrößenverteilung zu bestimmen. Die ermittelte Transformationskurve ermöglicht es, basierend auf der gemessenen Fluoreszenzflächenverteilung, die Partikelgrößenverteilung zu approximieren. Die Übertragbarkeit dieses Vorgehens wurde an PET erfolgreich evaluiert.
Die vorliegende Arbeit behandelt die Materialkompatibilität von Tracern und Polymeren und erläutert die physikalischen Effekte, die für die Material- und Produktidentifikation relevant sind. Aus technischer Sicht zeigen die Untersuchungen vielversprechende Ergebnisse, um mittels Tracereinsatz die Sortierung zu verbessern und folglich höherwertige Rezyklate zu erhalten. Darüber hinaus sollten die Untersuchungen auf weitere Material- und Werkstoffgruppen ausgeweitet werden. Die komplexe chemische Struktur der Polymeren sowie der Tracer kann die Entstehung anderer physikalischer Wechselwirkungseffekte bedingen. Des Weiteren ist kritisch anzumerken, dass mit dem Einsatz von Tracern die Gefahr der Tracerverschleppung und folglich eine erneute Verunreinigung der Stoffströme einhergeht. Andere innovative Identifikationstechnologien, wie Digitale Wassermarken oder Bilderkennung, zeigen dieses Problem nicht. Gegenwärtig befinden sich die Tracer-Technologie sowie die beiden anderen Identifikationstechnologien noch in der Entwicklungsphase. Aus diesem Grund mangelt es an praxiserprobten kreislaufwirtschaftlichen Kennzahlen zu Kosten, Durchsatz und Sortierreinheiten. Dennoch können diese Technologien dazu beitragen, die Bereitstellung von höherwertigen Rezyklaten zu fördern und somit die Schonung endlicher Ressourcen und des Umweltschutzes zu unterstützen.:1 Introduction
1.1 Motivation and Scope
1.2 Research Questions
2 Quality Challenges in Compounding
3 Influence of Tracer Additives on Polymer Properties
4 Fluorescence Signal Stability during Recycling
5 Factors Affecting the Tracer Fluorescence
6 Deriving Particle Size Distribution from Fluorescence Patterns
7 Discussion and Outlook
7.1 Synthesis of Research Results
7.2 Limitations
7.3 Outlook and Future Research
8 References
9 Annex: Full-Text Articles
9.1 Quality Aspects in the Compounding of Plastic Recyclate
9.2 Effects of Fluorescent Tracer Additives on PET During Material Recycling
9.3 Particle Size Distribution and Fluorescence Patterns of Tracer Additives in Polymer
Bandwidths of vocal tract resonances in physical models compared to transmission-line simulations
Get PDFThis study investigated how the bandwidths of resonances simulated by transmission-line models of the vocal tract compare to bandwidths measured from physical three-dimensional printed vowel resonators. Three types of physical resonators were examined: models with realistic vocal tract shapes based on Magnetic Resonance Imaging (MRI) data, straight axisymmetric tubes with varying cross-sectional areas, and two-tube approximations of the vocal tract with notched lips. All physical models had hard walls and closed glottis so the main loss mechanisms contributing to the bandwidths were sound radiation, viscosity, and heat conduction. These losses were accordingly included in the simulations, in two variants: A coarse approximation of the losses with frequency-independent lumped elements, and a detailed, theoretically more precise loss model. Across the examined frequency range from 0 to 5 kHz, the resonance bandwidths increased systematically from the simulations with the coarse loss model to the simulations with the detailed loss model, to the tube-shaped physical resonators, and to the MRI-based resonators. This indicates that the simulated losses, especially the commonly used approximations, underestimate the real losses in physical resonators. Hence, more realistic acoustic simulations of the vocal tract require improved models for viscous and radiation losses
The influence of socioeconomic aspects and hospital case volume on survival in colorectal cancer in Saxony, Germany
Get PDFBackground: Colorectal cancer (CRC) is one of the most common types of cancer in Western civilization and responsible for a high number of yearly deaths. Long-term outcome is influenced by many factors, potentially including socioeconomic aspects like income, education, and employment. Furthermore, annual surgical case volume plays a major role in achieving good oncological results. In our retrospective study, we evaluated the effect of socioeconomic deprivation and hospital volume on overall survival (OS) in the federal state of Saxony, Germany.
Methods: All patients with CRC who underwent surgery in Saxony, Germany between 2010 and 2020 and were living in Saxony at the time of diagnosis were included in our retrospective analysis. Uni- and multivariate analyses were conducted considering age, sex, tumor localization, UICC tumor stage, surgical approach (open/laparoscopic), number of resected lymph nodes, adjuvant chemotherapy, year of surgery, and hospital case volume. In addition, our model was adjusted for social disparity using the German Index of Socioeconomic Deprivation (GISD).
Results: A total of 24,085 patients were analyzed (15,883 with colon cancer and 8,202 with rectal cancer). Age, sex, UICC tumor stage and tumor localization were distributed as expected for CRC. Median overall survival time was 87.9 months for colon cancer and 110.0 months for rectal cancer. Univariate analysis revealed laparoscopic surgery (colon and rectum P < 0.001), high case volume (rectum: P = 0.002) and low levels of socioeconomic deprivation (colon and rectum P < 0.001) to be significantly associated with better survival. In multivariate analyses, the associations of laparoscopic surgery (colon: HR = 0.76, P < 0.001; rectum: HR = 0.87, P < 0.01), and mid-low to mid-high socioeconomic deprivation (colon: HR = 1.18–1.22, P < 0.001; rectum: HR = 1.18–1.36, P < 0.001–0.01) remained statistically significant. Higher hospital case volume was associated with better survival only in rectal cancer (HR = 0.89; P < 0.01).
Conclusion: In Saxony, Germany, better long-term survival after CRC surgery was associated with low socioeconomic deprivation, laparoscopic surgery and partly with high hospital case volume. Thus, there is a need to reduce social differences in access to high-quality treatment and prevention and increase hospital patient volume
Vibrational spectroscopy and multiphoton microscopy for label‑free visualization of nervous system degeneration and regeneration
Get PDFNeurological disorders, including spinal cord injury, peripheral nerve injury, traumatic brain injury, and neurodegenerative diseases, pose significant challenges in terms of diagnosis, treatment, and understanding the underlying pathophysiological processes. Label-free multiphoton microscopy techniques, such as coherent Raman scattering, two-photon excited autofluorescence, and second and third harmonic generation microscopy, have emerged as powerful tools for visualizing nervous tissue with high resolution and without the need for exogenous labels. Coherent Raman scattering processes as well as third harmonic generation enable label-free visualization of myelin sheaths, while their combination with two-photon excited autofluorescence and second harmonic generation allows for a more comprehensive tissue visualization. They have shown promise in assessing the efficacy of therapeutic interventions and may have future applications in clinical diagnostics. In addition to multiphoton microscopy, vibrational spectroscopy methods such as infrared and Raman spectroscopy offer insights into the molecular signatures of injured nervous tissues and hold potential as diagnostic markers. This review summarizes the application of these label-free optical techniques in preclinical models and illustrates their potential in the diagnosis and treatment of neurological disorders with a special focus on injury, degeneration, and regeneration. Furthermore, it addresses current advancements and challenges for bridging the gap between research findings and their practical applications in a clinical setting
Multimodal additive manufacturing of biomimetic tympanic membrane replacements with near tissue-like acousto-mechanical and biological properties
Get PDFThe three additive manufacturing techniques fused deposition modeling, gel plotting and melt electrowriting were combined to develop a mimicry of the tympanic membrane (TM) to tackle large TM perforations caused by chronic otitis media. The mimicry of the collagen fiber orientation of the TM was accompanied by a study of multiple funnel-shaped mimics of the TM morphology, resulting in mechanical and acoustic properties similar to those of the eardrum. For the different 3D printing techniques used, the process parameters were optimized to allow reasonable microfiber arrangements within the melt electrowriting setup. Interestingly, the fiber pattern was less important for the acousto-mechanical properties than the overall morphology. Furthermore, the behavior of keratinocytes and fibroblasts is crucial for the repair of the TM, and an in vitro study showed a high biocompatibility of both primary cell types while mimicking the respective cell layers of the TM. A simulation of the in vivo ingrowth of both cell types resulted in a cell growth orientation similar to the original collagen fiber orientation of the TM. Overall, the combined approach showed all the necessary parameters to support the growth of a neo-epithelial layer with a similar structure and morphology to the original membrane. It therefore offers a suitable alternative to autologous materials for the treatment of chronic otitis media
Insights on poster preparation practices in life sciences
Get PDFPosters are intended to spark scientific dialogue and are omnipresent at biological conferences. Guides and how-to articles help life scientists in preparing informative visualizations in poster format. However, posters shown at conferences are at present often overloaded with data and text and lack visual structure. Here, I surveyed life scientists themselves to understand how they are currently preparing posters and which parts they struggle with. Biologist spend on average two entire days preparing one poster, with half of the time devoted to visual design aspects. Most receive no design or software training and also receive little to no feedback when preparing their visualizations. In conclusion, training in visualization principles and tools for poster preparation would likely improve the quality of conference posters. This would also benefit other common visuals such as figures and slides, and improve the science communication of researchers overall
Numerical 3D-bifurcation analysis of star-shaped crack patterns using the energy method
Get PDFThe present research deals with a three-dimensional (3D) Finite Element Method (FEM) bifurcation analysis based on the global mechanical potential that can be used to find the parameters at which a crack pattern changes. In our case we want to analyze at which point the star-shaped shrinkage cracks in an aqueous colloidal suspension filled in a glass cylinder change from four to three or two cracks growing. The driving force for the crack growth is shrinkage caused by diffusion controlled drying. The 3D crack front geometry is described efficiently by using a Fourier series approach. Based on steady-state crack growth, the Fourier coefficients are determined in a first step using an optimization algorithm. As a result, the time dependent crack growth can be determined. In a second step, the bifurcation point is determined by an eigenvalue analysis of the second order derivatives of the potential energy of the system. If the lowest eigenvalue reaches zero the fundamental solution becomes unstable and a transition will occur. Our analysis shows that the transition from four to two cracks is preferred over the transition from four to three cracks
On different classes of constitutive descriptions in finite electro-mechanics: Computational modelling of isotropic and anisotropic electro-active materials
Get PDFVarious constitutive formulations can be employed to simulate the coupled behaviour of electro-active polymers (EAP). Those distinct mathematical descriptions vary with respect to the manner in which the electric field is coupled to the deformation. However, in principle, they are all capable of emulating the finite coupled response of EAP. The underlying coupling mechanism of largely deformable materials can be identified through experimental characterization. This contribution addresses the constitutive and finite element modelling of the actuation response of both isotropic and anisotropic EAP, where different material formulations are considered and implemented within a finite element framework. Those various material formulations are mathematically treated and employed to simulate electro-mechanical experiments of dielectric materials. Existing coupled electro-mechanical tests of active materials are referred to, where it is sought to employ different constitutive models to fit the experimental observations. Within the undertaken study, the capability of different descriptions to predict electro-mechanical instabilities is evaluated. Regarding the numerical implementation of the model, it is referred to an electro-mechanical Q1P0 finite element formulation. After performing the study and fitting experimental results associated to isotropic materials, the actuation response of several anisotropic EAP-based structures is emulated