Design of variable acceptance sampling plan for exponential distribution under uncertainty

In an acceptance monitoring system, acceptance sampling techniques are used to increase production, enhance control, and deliver higher-quality products at a lesser cost. It might not always be possible to define the acceptance sampling plan parameters as exact values, especially, when data has uncertainty. In this work, acceptance sampling plans for a large number of identical units with exponential lifetimes are obtained by treating acceptable quality life, rejectable quality life, consumer's risk, and producer's risk as fuzzy parameters. To obtain plan parameters of sequential sampling plans and repetitive group sampling plans, fuzzy hypothesis test is considered. To validate the sampling plans obtained in this work, some examples are presented. Our results are compared with existing results in the literature. Finally, to demonstrate the application of the resulting sampling plans, a real-life case study is presented.Comment: This work is submitted to Journal of the Applied Mathematics, Statistics and Informatics (JAMSI) for revie

Holistic process development to mitigate proteolysis of a subunit rotavirus vaccine candidate produced in Pichia pastoris by means of an acid pH pulse during fed-batch fermentation.

To meet the challenges of global health, vaccine design and development must be reconsidered to achieve cost of goods as low as 15¢ per dose. A new recombinant protein-based rotavirus vaccine candidate derived from non-replicative viral subunits fused to a P2 tetanus toxoid CD4(+) T cell epitope is currently under clinical development. We have sought to simplify the existing manufacturing process to meet these aims. To this end, we have taken a holistic process development approach to reduce process complexity and costs while producing a product with the required characteristics. We have changed expression system from Escherichia coli to Pichia pastoris, to produce a secreted product, thereby reducing the number of purification steps. However, the presence of proteases poses challenges to product quality. To understand the effect of fermentation parameters on product quality small-scale fermentations were carried out. Media pH and fermentation duration had the greatest impact on the proportion of full-length product. A novel acidic pH pulse strategy was used to minimize proteolysis, and this combined with an early harvest time significantly increased the proportion of full-length material (60-75%). An improved downstream process using a combination of CIEX and AIEX to further reduce proteases, resulted in maintaining product quality (95% yield)

Holistic process development to mitigate proteolysis of a subunit rotavirus vaccine candidate produced in Pichia pastoris by means of an acid pH pulse during fed‐batch fermentation

To meet the challenges of global health, vaccine design and development must be reconsidered to achieve cost of goods as low as 15¢ per dose. A new recombinant protein‐based rotavirus vaccine candidate derived from non‐replicative viral subunits fused to a P2 tetanus toxoid CD4(+) T cell epitope is currently under clinical development. We have sought to simplify the existing manufacturing process to meet these aims. To this end, we have taken a holistic process development approach to reduce process complexity and costs while producing a product with the required characteristics. We have changed expression system from Escherichia coli to Pichia pastoris, to produce a secreted product, thereby reducing the number of purification steps. However, the presence of proteases poses challenges to product quality. To understand the effect of fermentation parameters on product quality small‐scale fermentations were carried out. Media pH and fermentation duration had the greatest impact on the proportion of full‐length product. A novel acidic pH pulse strategy was used to minimize proteolysis, and this combined with an early harvest time significantly increased the proportion of full‐length material (60–75%). An improved downstream process using a combination of CIEX and AIEX to further reduce proteases, resulted in maintaining product quality (95% yield)

Innovations in ex vivo light sheet fluorescence microscopy

Light Sheet Fluorescence Microscopy (LSFM) has revolutionized how optical imaging of biological specimens can be performed as this technique allows to produce 3D fluorescence images of entire samples with a high spatiotemporal resolution. In this manuscript, we aim to provide readers with an overview of the field of LSFM on ex vivo samples. Recent advances in LSFM architectures have made the technique widely accessible and have improved its acquisition speed and resolution, among other features. These developments are strongly supported by quantitative analysis of the huge image volumes produced thanks to the boost in computational capacities, the advent of Deep Learning techniques, and by the combination of LSFM with other imaging modalities. Namely, LSFM allows for the characterization of biological structures, disease manifestations and drug effectivity studies. This information can ultimately serve to develop novel diagnostic procedures, treatments and even to model the organs physiology in healthy and pathological conditions.This work was produced with the support of the Spanish Ministry of Science, Innovation and Universities (TEC2016-78052-R, RTC-2017-6600-1, PID2019-109820RB-100, FPU19/02854)

Can a Significance Test Be Genuinely Bayesian?

The Full Bayesian Significance Test, FBST, is extensively reviewed. Its test statistic, a genuine Bayesian measure of evidence, is discussed in detail. Its behavior in some problems of statistical inference like testing for independence in contingency tables is discussed

A Review of Modern Multiple Hypothesis Testing, with particular attention to the false discovery proportion

In the last decade a growing amount of statistical research has been devoted to multiple testing, motivated by a variety of applications in medicine, bioinformatics, genomics, brain imaging, etc. Research in this area is focused on developing powerful procedures even when the number of tests is very large. This paper attempts to review research in modern multiple hypothesis testing with particular attention to the false discovery proportion, loosely defined as the number of false rejections divided by the number of rejections. We review the main ideas, stepwise and augmentation procedures; and resampling based testing. We also discuss the problem of dependence among the test statistics. Simulations make a comparison between the procedures and with Bayesian methods. We illustrate the procedures in applications in DNA microarray data analysis. Finally, few possibilities for further research are highlighted

Efficiency Improvement of Organic Light-Emitting Diodes: Development of Novel Fabrication and Optical Evaluation Concepts

Organic Light-Emitting Diodes (OLEDs) currently advance in the display market due to their unique image quality. Innovations profit from further extraordinary properties such as mechanical flexibility, optical transparency and large area coverage. Despite considerable progress in development, high costs and moderate efficiencies hamper the entry into the lighting market. However, there still is enormous potential for efficiency improvement. Current problems are the work-intensive search for best material combinations and large amounts of trapped light in the flat OLED geometry. This thesis develops novel concepts for improving the efficiency of OLEDs: An optimized fabrication, a systematic evaluation of light outcoupling structures by proposing a new metric, and an examination of efficiency limitations with optical simulations to identify options for action. The optimization of OLEDs is closely related to the properties of the individual molecules, while the fabrication process is often neglected. However, literature has shown that vapor deposited organic glasses can exhibit extraordinary high stabilities when fabricated at the right conditions. The substrate temperature is therefore set to 85 % of the materials conventional glass transition temperature Tg while the deposition rates are kept below < 0.1 nm/s. This concept is adapted and the glass forming molecule TPBi is fabricated as stable host and electron transporter in a simple OLED. Efficiency and lifetime improvement could be achieved with four different phosphorescent emitters. For Ir(ppy)2(acac) the External Quantum Efficiency (EQE) at 100 cd/m² is enhanced from 19.4 to 24.0 % and the lifetime LT 70 at 1,000 cd/m² from 14.8 to 74.2 h, i.e. the time in which the initial luminance drops to 70 % is five times higher. The origin is found in improved radiative and electrical efficiency. This fabrication concept enables an additional optimization path besides material development. Next, the high refractive index of organic materials lead to light confinement through total internal reflection. Many light outcoupling strategies have been developed, but their direct comparison is difficult through the diversity of used structures and OLEDs. This thesis proposes a new efficiency metric, the Efficiency of Light Outcoupling Structures (ELOS), that states the effectiveness of a light outcoupling structure. It weights experimental efficiency enhancement to theoretically maximal gain that is simulated. It was found that a glass half-sphere extracts about 80 % photons from the OLED substrate, while a combination of a diffraction grating with the half-sphere extracts at best 43 % from the whole OLED. The corresponding EQEs are 32.5 % and 36.5 %. The ELOS promotes a systematic search for a universally efficient light outcoupling structures, because it removes misinterpretation through the specifically used OLED. Lastly, optical investigations have found the following statements for bottom-emitting OLEDs: Highest EQEs with external light outcoupling structures are reached for 3/4 λ cavities. EQEs of more than 90 % could be reached with a low refractive index electron transport layer in combination with a high refractive index substrate and ideal external light outcoupling. For top-emitting OLEDs, the thin film interference can be exploited to shift the emission color of sky-blue emitter towards blue. Commission Internationale de l’Éclairage (CIE) color coordinates of (0.127/0.168) could experimentally be achieved with an emitter that has (0.213/0.374). The color tuning reduces EQE, but therefore exploits higher lifetimes of sky-blue emitters. This opens an alternative to reach deep blue emission besides material development, which is a current challenge for displays.Organische Leuchtdioden (OLEDs) etablieren sich derzeit im Display-Markt aufgrund ihrer einzigartigen Bildqualität. Innovationen profitieren zudem von weiteren außergewöhnlichen Eigenschaften wie z.B. mechanische Flexibilität, optische Transparenz und Großflächigkeit. Obwohl es bereits beträchtliche Weiterentwicklungen gab, erschweren hohe Kosten und moderate Effizienzen den Markteintritt in den Beleuchtungssektor. Dabei gibt es noch enormes Potential für Effizienzsteigerungen. Derzeitige Probleme sind die aufwändige Suche nach den besten Material(-kombinationen) und große Verluste durch Licht, welches im flachen Bauteil verbleibt. In dieser Dissertation werden deshalb neuartige Konzepte entwickelt, um die Effizienzsteigerung voranzutreiben: Eine optimierte Herstellung, eine systematische Untersuchung von Lichtauskoppelstrukturen mittels einer neuen Metrik und die Untersuchung von Effizienzlimitierungen mithilfe von optischen Simulationen, um weitere Möglichkeiten zur Verbesserung zu identifizieren. Die Optimierung von OLEDs ist eng verbunden mit der Materialsuche, wobei der Herstellungsprozess oft vernachlässigt wird. Allerdings konnte in der Literatur gezeigt werden, dass aufgedampfte organische Gläser außergewöhnlich stabil sein können, wenn die Herstellungsbedingungen optimiert werden. Dafür muss die Substrattemperatur auf etwa 85 % der gewöhnlichen Glasübergangstemperatur Tg gesetzt werden, während das Material mit niedrigen Raten von < 0,1 nm/s aufgetragen wird. Dieses Konzept wird übernommen für das Glasformer Molekül TPBi, welches als stabile Matrix und Elektronentransporter in einer einfachen OLED realisiert wird. Damit wird eine Effizienz- und Lebensdauerverbessung für vier phosphoreszente Emittermoleküle erreicht. Für Ir(ppy)2(acac) wird die externe Quanteneffizienz (EQE) bei 100 cd/m² von 19,4 auf 24,0 % erhöht und die Lebensdauer LT 70 bei 1000 cd/m² von 14,8 auf 74,2 h, d.h. die Zeit, bis die ursprüngliche Helligkeit auf 70 % fällt, wird verfünffacht. Ursache dafür ist eine verbesserte elektrische Effizienz und Strahlungseffizienz. Diese Herstellungsoptimierung eröffnet neben der Materialsuche eine weitere Möglichkeit für OLED Verbesserungen. Weiterhin führt der hohe Brechungsindex organischer Materialien zu Lichteinschluss im Bauteil durch totale interne Reflexion. Um zusätzliches Licht zu extrahieren, wurden viele Lichtauskoppelstrukturen entwickelt, welche sich jedoch aufgrund der Vielfalt der Strukturen und OLEDs nur schwer vergleichen lassen. Diese Arbeit schlägt eine neue Effizienzgröße vor, die sogenannte Effizienz von Lichtauskoppelstrukturen (ELOS), welche die Effektivität von den Strukturen angibt. Sie vergleicht die experimentell bestimmte mit der maximal erwartbaren Verbesserung, welche mit optischen Simulationen berechnet wird. Damit konnte gezeigt werden, dass eine Glashalbkugel etwa 80 % aller Photonen vom OLED Substrat extrahiert, während eine Kombination von Streugittern mit Glashalbkugel bestenfalls 43 % der verbleibenden Photonen in der gesamten OLED extrahiert. Die jeweiligen EQEs sind 32,5 % und 36,5 %. Die ELOS fördert eine systematische Suche nach den universell am besten funktionierenden Lichtauskoppelstrukturen, weil Missinterpretationen durch die jeweilig verwendeten OLEDs verringert werden. Letztendlich haben die optischen Untersuchungen folgende Aussagen für bottom emittierenden OLEDs gefunden: Die höchste EQE mit externen Lichtauskoppelstrukturen werden mit 3/4 λ Kavitäten erreicht. EQEs von mehr als 90 % könnten erreicht werden durch Kombination von niedrigbrechenden Elektronentransportschichten, hochbrechenden Substraten und idealen Lichtauskoppelstrukturen. Für top emittierende OLEDs kann Dünnschichtinterferenz ausgenutzt werden, um die Farbe von himmelblauen Emittern zu tiefblau zu verschieben. CIE Farbkoordinaten von (0.127/0.168) konnten experimentell erreicht werden mit einem Emitter von (0.213/0.374). Die Farbverschiebung verringert zwar die EQE, allerdings kann so die höhere Lebensdauer von himmelblauen Emittern ausgenutzt werden. Damit wird eine Alternative zur Materialsuche geschaffen, um tiefblaue Farbe zu erreichen, was eine derzeitige Herausforderung für Displays ist