Two-stage maximum likelihood estimation procedure for parallel constant-stress accelerated degradation tests.

[[abstract]]Abstract—The parallel constant-stress accelerated degradation test (PCSADT) is a popular method used to assess the reliability of highly reliable products in a timely manner. Although the maximum likelihood (ML) method is commonly utilized to estimate the PCSADT parameters, the explicit forms of the ML estimators, and their corresponding Fisher information matrix are usually difficult to obtain. In this article, we propose a two-stage ML (TSML) estimation procedure for a time-transformed model. In the proposed procedure, all the TSML estimators not only have explicit expressions but also possess consistency and asymptotic normality. Hence, this method is tractable for reliability engineers. Furthermore, the TSML estimators can provide constructive information about the unknown accelerated relationship law. The proposed method is also applied to analyze light-emitting diode data and compare the performance of our estimation procedures with the ML method via simulations.[[notice]]補正完

Maintaining the Integrity Over Wear Time of a Hydrocolloid-based Ostomy Adhesive Whilst Maintaining Skin Barrier Function

In this extensive body of work, a thorough exploration delves into hydrocolloid based adhesives, with a focus on addressing challenges faced by stoma patients, particularly the susceptibility of ostomy adhesives to breakdown upon exposure to liquids. Stoma patients, compelled to wear pouching systems continuously, encounter issues like the compromise of skin barrier integrity, leading to medical adhesive-related skin injuries. The primary objective of this thesis is to reinforce the structural integrity of ostomy adhesives while preserving the skin barrier during pouching system use, an aspect often overlooked in current literature due to the hydrophilic nature of hydrocolloid based adhesives. The study introduces novel aims, examining the potential link between handedness and the preferred direction of adhesive removal, and its impact on peristomal skin complications as well as a novel skin capacitive imagery stitching technique. Another goal involves developing hierarchical structures on adhesive surfaces to enhance integrity, initial tack, and minimize skin contact for optimal skin health. The introduction provides a detailed breakdown of hydrocolloid-based ostomy adhesives, stoma anatomy, and the purpose of pouching systems. A comprehensive literature review, utilizing the PICO approach, encompasses stoma anatomy, physiology, indications for stoma surgery, and methods for assessing skin health. The review explores various methodologies to improve the durability of hydrocolloid-based adhesives, incorporating hydrodynamics, crosslinking, and layering systems. The potential influence of handedness on adhesive removal techniques is examined, considering its impact on peristomal skin complications. Results reveal the consistent performance of Welland Medical Ltd.'s hydrocolloid based adhesive but highlight the need for improved integrity over wear time. Strategies include modifying sodium-carboxymethylcellulose degree of substitution and increasing pectin degree of esterification, resulting in enhanced fluid handling capabilities and reduced susceptibility to degradation. Residual testing indicates that residual particles on the skin can impair the barrier function, remedied by a silicone-based adhesive remover. Surveys show that a patient's dominant hand and following the skin's natural langer lines during adhesive removal may minimize skin trauma. The results also show that structured surface profiles on hydrocolloid-based adhesive surfaces impact the skin's functional barrier recovery time. The research goal of this project and its objectives have been reached, the approaches have been explained clearly and implementations have been assessed using experimental findings. This project's findings contribute to advancements in ostomy care by enhancing adhesive performance, understanding patient behaviour, and improving the overall user experience. It also facilitates the efficient detachment of the adhesive from the skin surface

Structure-functionality relationship of collagen scaffolds for tissue engineering

Tissue engineering is a promising technology that enables scientists to create artificial organs or replace damaged tissues using animal cells and other components. For successful tissue regeneration, many factors should be taken into account, however, three components are most crucial: cell, scaffold, and soluble factor(s). In order to check the functionality after regeneration of desired tissues, various approaches have been attempted, depending on the physical, biological, and chemical properties of the tissues. Recently, the importance of the extracellular matrix (ECM) microstructure is being considered to be important in this regard. The ECM is closely associated with various functional properties of the tissues including mechanical properties, diffusivity, and hydraulic conductivity or permeability. Besides providing structural support and determining the physical and functional properties, the ECM plays various roles in tissue physiology by regulating cell morphology, growth and intercellular signaling. The ECM can also be reconfigured by cells during tissue remodeling and wound healing. In this thesis, in order to investigate the structure-functionality relationship of engineered tissues (ETs), computational modeling and experimental studies were performed based on the following three topics: (1) the effect of different ECM structures on the tissue transport property, (2) the effect of the different ECM structures on the cell functionality and subsequent tissue mechanical property, and (3) the evaluation of functionality of new vessel networks formed by modulation of ECM structures. ^ The first study developed computational models (i.e., parameter- and image-based models) using experimental data to predict transport properties (i.e.,permeability and diffusivity) of two different microstructural matrices (i.e., monomer and oligomer) for tissue functionality. The developed computational models underestimated the permeability result compared to what was obtained experimentally. The image- and parameter-based models developed in the present study were able to predict values closest to the experiment data, when compared with previously reported models of permeability. For diffusivity, the computational results showed a similar trend and magnitude to the experimental ones. ^ During cryopreservation of tissues, freezing-induced structural deformation of the tissues and cells occurs due to formation of ice within the intracellular and extracellular spaces. Several studies focused on developing optimal combinations of cryoprotective agent (CPA) and freeze/thaw (F/T) protocols for functional tissue and cell preservation. In the second study, a hypothesis was tested that the modulation of the cytoskeletal structure can mitigate the freezing-induced changes of the functionality, therefore, may reduce the amount of CPA necessary to preserve the tissue\u27s functionality during cryopreservation. In order to test the above hypothesis, the engineered tissues (ETs) were exposed to various F/T conditions with or without CPAs, and the freezing-induced cell-fluid-matrix interactions and subsequent functional properties of the ETs were assessed. Our result showed that, the use of only a small concentration of CPA was very successful in completely preserving the elastic modulus and the viscous friction to the state of the unfrozen 3D stressed structure (STR). This result underscores the importance of CPA in preserving the cytoskeleton structure and how that impacts functional properties of the tissue after freeze-thaw cycles. ^ The third study performed the parametric study to estimate endothelium hydraulic conductivity for vessel functionality. Currently, it is known that formation of vasculatures within the tissues is the most difficult aspect of tissue engineering. Moreover, a method to evaluate new vessel functionality has not been well-established to date. Therefore, a new method with the osmotic pressure-driven vessel deformation and the poroelastic theory was developed using new vessel networks formed by vasculogenesis for hydraulic conductivity estimation. Results showed that the hydraulic conductivity was more sensitive to the elastic modulus compared to other parameters. When the elastic modulus with 10 - 100 Pa and Possions\u27s ratio with 0.3 were applied, the hydraulic conductivity was well-matched with the previously reported hydraulic conductivity

Nanoengineered Biomaterials for Cell and Therapeutic Delivery

Direct-write extrusion bioprinting, a form of additive manufacturing, is a useful technique to recapitulate anatomical complexity for tissue engineering applications. However, bioprinting has hit a bottleneck in progress due to the lack of available bioinks with high printability, mechanical strength, and biocompatibility. Here, we report a family of hydrogel-based bioinks for extrusion bioprinting from poly (ethylene glycol) (PEG) and two-dimensional (2D) nanoparticles. PEG, a non-fouling easily modifiable polymer, combined with biocompatible Laponite XLG nanoparticles (2D nanosilicates) to obtain shear-thinning hydrogel bioinks. Electrostatic interactions between nanoparticles and hydrogen-bonding between polymer and nanoparticles govern the flow behavior and printability of bioink. The evaluation of hydrogel bioink using flow sweeps, peak holds, and dynamic oscillatory rheology, suggest that minimum shear-thinning index of ~0.3, solution viscosities >1000 Pa·s, and 80% recovery within 30s are necessary for printing high fidelity constructs. Mechanically stiff 3D printed structures are obtained by covalently crosslinking polymeric chains using ultraviolet (UV) light. Modifications to the PEG system through inclusion of dithiothreitol linkage or combining with gelatin methacrylate are used to control matrix degradation, cell adhesion properties, and therapeutic release. We envision that PEG bioinks can be used to print complex, large-scale, cell-laden tissue constructs with high structural fidelity and mechanical stiffness for applications in custom bioprinted scaffolds and tissue engineered implants

Application of Polymeric Hollow-Fiber Membranes in Air Filtration

Membrány z dutých vláken jsou široce využívány v aplikacích týkajících se úpravy kapalin jako např. při čištění odpadních vod, v membránových kontaktorech a bioreaktorech, membránové destilaci apod. I když jsou často využívány při separacích směsí plynů, je jejich použití pro mechanickou filtraci aerosolů velmi vzácné. Tato práce se zabývá filtrací vzduchu pomocí polypropylenových membrán z dutých vláken včetně jejich filtrační účinnosti, tlakových ztrát a také zanášením při dlouhodobé filtraci. Filtrační účinnost byla proměřena za použití různých aerosolů jako TiO2 a síran amonný. Tlakové ztráty byly měřeny při různých konfiguracích, tj. různé filtrační ploše a průměru vlákna membrány. Zanášení membrán bylo testováno použitím normovaného prachu definovaného normou ANSI/ASHRAE 52.2. Predikční modely pro filtrační účinnost a permeabilitu/tlakovou ztrátu membrány byly aplikovány na parametry membrán z dutých vláken a porovnány. Tyto membrány mají velikost pórů kolem 90 nm a poměrně nízkou porositu a tím vysoký potenciál pro separaci nanočástic ze vzduchu. Dále byla provedena analýza filtračního koláče a vyhodnocení energetických nároků a porovnány s teoretickými modely. V závěru práce je nastíněn odhad ceny životního cyklu při filtraci pomocí těchto membrán.Hollow-fiber membranes (HFMs) have widely been applied to many liquid treatment applications such as wastewater treatment, membrane contactors/bioreactors, membrane distillation etc. Despite the fact that HFMs are widely used for gas separation from gas mixtures, their use for mechanical filtration of aerosols is very scarce. This work studied filtration performance of polypropylene HFMs including filtration efficiency, pressure drop and pressure drop evolution with long-term dust loading. Filtration efficiency was measured using different challenging aerosols including micronized titanium dioxide powder and aerosolized ammonium sulfate. Pressure drop was measured in various configurations, including different HFM area and fiber diameter. Pressure drop evolution with long-term particle loading was carried out using a challenge dust as defined in ANSI/ASHRAE 52.2 standard. Mathematical models developed for prediction of air filtration efficiency and membrane permeability/pressure drop were compared applying them on the structural parameters of the HFMs. These membranes are characteristic of pore diameters of about 90 nm and relatively low porosity, thus high potential for nanoparticle removal from air. Furthermore, analysis on cake pressure drop and evaluation of energy demands for fun operation were done and compared with theoretically predicted values. Finally, an attempt to estimate life-cycle cost of air filtration using HFMs was outlined.

IMPACT OF HEMODYNAMIC VORTEX SPATIAL AND TEMPORAL CHARACTERISTICS ON ANALYSIS OF INTRACRANIAL ANEURYSMS

Subarachnoid hemorrhage is a potentially devastating pathological condition in which bleeding occurs into the space surrounding the brain. One of the prominent sources of subarachnoid hemorrhage are intracranial aneurysms (IA): degenerative, irregular expansions of area(s) of the cerebral vasculature. In the event of IA rupture, the resultant subarachnoid hemorrhage ends in patient mortality occurring in ~50% of cases, with survivors enduring significant neurological damage with physical or cognitive impairment. The seriousness of IA rupture drives a degree of clinical interest in understanding these conditions that promote both the development and possible rupture of the vascular malformations. Current metrics for the assessment of this pathology rely on measuring the geometric characteristics of a patient\u27s vessel and/or IA, as well as the hemodynamic stressors existing along the vessel wall. Comparatively less focus has been granted toward understanding the characteristics of much of the bulk-flow within the vasculature and how it may play a role in IAs. Specifically, swirling hemodynamic flow (vortices) have been suggested as a condition which exacerbates vascular changes leading to IAs, yet quantified measurements of the spatial and temporal characteristics of vortices remain overlooked. This dissertation studies the role of the spatial and temporal characteristics of vortex flow and how it plays a role on IA pathology. Its chapters are a collection of five (5) works into this matter. First, established methods for the identification of vortices was investigated, and a novel method for vortex identification and quantification of their characteristics was developed to overcome the limitations of previous methods. Second, the developed method for vortex identification/quantification was then applied to a simulation study to improve predictive models aimed at predicting areas of IA development from those unlikely to suffer this pathology. Third, assessing how the simulated repair of one IA impacts changes to hemodynamic conditions within other nearby un-repaired IAs in a multiple IA system. Fourth, it was determined if vortex identification/quantification improved predictive models aimed at differentiation ruptured from unruptured IAs. Fifth, impart vortical flow of differing characteristics onto cultured vascular cells to determine if vortex stability imparts varied levels of cellular changes

Statistical mechanics of non equilibrium matter: from minimal models to morphogen gradients

Living systems are by definition far from thermodynamic equilibrium, a condition that can be maintained only at the cost of a continuous injection of energy at the microscale, e.g. via cellular metabolic processes, and dissipation into the surrounding environment. The absence of thermodynamic equilibrium, formalised in the breaking of the global detailed balance condition, allows for a wealth of exotic and often counterintuitive phenomena. Our understanding of the capabilities and limitations of living matter has been greatly informed by thermodynamic approaches, which have to be generalised with respect to their traditional counterparts in order to deal with systems subject to strong random fluctuations. The resulting toolkit of stochastic thermodynamics, in particular the concept of entropy production, gives us a quantitative handle on the degree of "non-equilibriumness" of such stochastic processes. Recently, stochastic thermodynamics has benefitted from cross-contamination with the field-theoretic literature and the techniques developed in the latter for the study of collective behaviour have opened the doors to the thermodynamic characterisation of increasingly complex systems. Starting from minimal mathematical models of single active particles and moving up across scales to the level of morphogenetic processes in real organisms (in particular, the formation of morphogen gradients), this thesis contributes to laying the foundations for a bridge between physical understanding and biological insight. While the focus is here on generic mechanisms and on the development of theoretical tools, the applicability to specific experimental scenarios will be pointed out where relevant.Open Acces