Evaluation of fast spectroscopic analysis techniques for freeze-dried live, attenuated virus vaccines

Freeze-drying is today the preferred method for stabilizing live, attenuated virus vaccines. Despite its wide use in the pharmaceutical industry, freeze-drying formulation and process development of live, attenuated virus vaccines are still performed by trial-and-error experimental work resulting in sub-optimal processes. The stabilization and destabilization mechanisms of the live, attenuated viruses during freeze-drying, are still not fully understood. The molecular complexity of live, attenuated viruses, the multiple destabilization pathways and the lack of analytical techniques allowing the measurement of physicochemical changes in the antigen’s structure during and after lyophilization partly explain this lack of knowledge. Therefore, the possibility to apply spectroscopic process analytical tools, in particular NIR and FTIR spectroscopy, to (i) evaluate live, attenuated viruses and their interactions with the stabilizer(s) in freeze-dried samples, (ii) understand virus destabilization mechanisms during storage and (iii) develop practical applications using chemometric models to predict critical end product quality parameters, has been evaluated in this thesis

Design behaviors : programming the material world for responsive architecture

The advances of material science, coupled with computation and digital technologies, and applied to the architectural discipline have brought to life unprecedented possibilities for the design and making of responsive, collectively created and intelligent environments. Over the last two decades, research and applications of novel active materials, together with digital technologies such as Ubiquitous Computing, Human-Computer Interaction, and Artificial Intelligence, have introduced a model of Materially Responsive Architecture that presents unique possibilities for designing novel performances and behaviors of the architectural Beyond the use of mechanical systems, sensors, actuators or wires, often plugged into traditional materials to animate space, this dissertation proves that matter itself, can be the agent to achieve monitoring, reaction or adaptation with no need of any additional mechanics, electrical or motorized systems. Materials, therefore, become bits and information uniting with the digital world, while computational processes, such as algorithmic control, circular feedback, input or output, both drive and are driven by the morphogenetic capacities of matter, uniting, therefore, with the material world. Through the applications and implications of Materially Responsive Architecture we are crossing a threshold in design where physicality follows and reveals information through time and through dynamic configurations. Design is not limited to a finalised form but rather associated to a performance, where the final formal outcome consists in a series of animated and organic topologies rather than static geometries and structures. This new paradigm, is referred to, in this thesis, as the Design Behaviors paradigm (in the double sense of "behaviors of design" and "designing behaviors"), and is characterized by unique exchanges and dialogues between users and the environment, facilitated by the conjunction of human, material and computational intelligence. Buildings, objects and spaces are able to reconfigure themselves, in both atomic and macro scale, to support environmental changes and users' needs, behavioral and occupational patterns. At the same time the Design Behaviors paradigm places not only matter and the environment at the center of design and morphogenesis, but also the users, that become active participants of their built environment and play the final creative role. This paradigm shift, boosts new relations among the human's perception and body and the inhabited space. The new design paradigm is also a new cultural one, in which statics, repetition and Cartesian grids, traditionally related with safety, orientation and comfort, give way to motion, unpredictability and organic principles of evolution. Materially Responsive Architecture and the Design Behaviors paradigm define uniquely enhanced "environments" and "ecologies" where human, nature, artifice and technology collectively and evolutionally co-exist within a framework of increased consciousness and awareness. This thesis argues that, while there is no doubt that our future cities will consist in an extensive layer of distributed sensors, actuators and digital interfaces, they will also consist in an additional layer of novel materials, that are dynamic and soft, rather than rigid and hard, able to sense as sensors, actuate as motors, and be programmed as a software. The new materiality of our cities relies on the advances of material science, coupled with the cybernetic and computational power, and can be actuated by the environment to change states (Re-Active Matter), can be controlled by the users to respond (Co-Active Matter), and eventually can be designed and programmed to learn and evolve as living organisms do (Self-Active Matter). The physical space of the city is, thus, the seamless intertwining of digital and material content, becoming an active agent in the dynamic relationship between the environment and humans.Los avances en la ciencia de los materiales, junto con la computación y las tecnologías digitales, y aplicados a la disciplina arquitectónica, han dado vida a posibilidades sin precedentes para el diseño y la realización de entornos responsivos, inteligentes y creados de forma colectiva. En las últimas dos décadas, la investigación y aplicación de nuevos materiales activos junto con tecnologías digitales como la Computación Ubicua, la Interacción Hombre-Ordenador y la Inteligencia Artificial, han introducido el modelo de Materially Responsive Architecture (Arquitectura Materialmente Responsiva), que presenta posibilidades únicas para el diseño de nuevas actuaciones y comportamientos del espacio arquitectónico. Más allá del uso de sistemas mecánicos, sensores, o motores, a menudo conectados a materiales tradicionales para activar el espacio, esta disertación demuestra que la materia en sí misma puede ser el agente que consiga monitoreo o reactividad sin necesidad de añadir ningún sistema mecánico o eléctrico. Los materiales, en este caso, se convierten en bits e información fundiéndose con el mundo digital, mientras que los procesos computacionales, como el feedback circular y el input o output, a la vez impulsan y son impulsados por la capacidad morfogenética de la materia, uniéndose, por lo tanto, con el mundo material. A través de las aplicaciones y las implicaciones de la Materially Responsive Architecture, estamos cruzando un umbral en el diseño donde el mundo físico sigue y revela información a través de configuraciones dinámicas en el tiempo. El diseño no se limita a una forma finalizada, sino se relaciona a una performance, donde el resultado formal final consiste en una serie de topologías orgánicas y animadas en lugar de estructuras y geometrías estáticas. En esta tesis doctoral, este nuevo paradigma se denomina paradigma de Design Behaviours (en el doble sentido de "comportamientos de diseño" y de "diseño de comportamientos") y se caracteriza por intercambios únicos entre el usuario y el entorno, facilitados por la conjunción de inteligencia humana, material y computacional. Los edificios, objetos y espacios pueden reconfigurarse a sí mismos, tanto a nivél atómico como a macro escala, para responder a los cambios ambientales y a las necesidades de los usuarios. Al mismo tiempo, el paradigma Design Behaviors coloca en el centro del diseño y la morfogénesis no solo la materia y el medio ambiente, sino también a los usuarios, que se convierten en participantes de su entorno construido y desempeñan el papel creativo final. El nuevo paradigma define "entornos" y "ecologías" aumentados de manera singular, donde el ser humano, la naturaleza, el artificio y la tecnología coexisten de manera colectiva y evolutiva dentro de un marco de mayor conciencia consciente. El nuevo paradigma de diseño es también un nuevo paradigma cultural, en el que las redes estáticas, repetitivas y cartesianas, tradicionalmente relacionadas con la seguridad, la orientación y el confort, dan paso al movimiento, la imprevisibilidad y la evolución orgánica. Esta tesis sostiene que, si bien no hay duda de que nuestras ciudades futuras consistirán en una capa extensa de sensores distribuidos e interfaces digitales, también contarán con una capa adicional de materiales dinámicos y suaves, en lugar de rígidos y duros, capaces de sentir como sensores, actuar como motores y ser programados como un software. La nueva materialidad de nuestras ciudades puede ser activada por el medio ambiente para cambiar su estado (Re-Active Matter), puede ser controlada por los usuarios para responderles (Co-Active Matter), y eventualmente puede diseñarse y programarse para aprender y evolucionar por sí misma así como lo hacen los organismos vivos (Self-Active Matter). El espacio físico de la ciudad es, por lo tanto, el entrelazado holístico entre contenido digital y material, convirtiéndose en un agente activo en la relación dinámica entre el medio ambiente y los humanos

Efficient Numerical Solution of Large Scale Algebraic Matrix Equations in PDE Control and Model Order Reduction

Matrix Lyapunov and Riccati equations are an important tool in mathematical systems theory. They are the key ingredients in balancing based model order reduction techniques and linear quadratic regulator problems. For small and moderately sized problems these equations are solved by techniques with at least cubic complexity which prohibits their usage in large scale applications. Around the year 2000 solvers for large scale problems have been introduced. The basic idea there is to compute a low rank decomposition of the quadratic and dense solution matrix and in turn reduce the memory and computational complexity of the algorithms. In this thesis efficiency enhancing techniques for the low rank alternating directions implicit iteration based solution of large scale matrix equations are introduced and discussed. Also the applicability in the context of real world systems is demonstrated. The thesis is structured in seven central chapters. After the introduction chapter 2 introduces the basic concepts and notations needed as fundamental tools for the remainder of the thesis. The next chapter then introduces a collection of test examples spanning from easily scalable academic test systems to badly conditioned technical applications which are used to demonstrate the features of the solvers. Chapter four and five describe the basic solvers and the modifications taken to make them applicable to an even larger class of problems. The following two chapters treat the application of the solvers in the context of model order reduction and linear quadratic optimal control of PDEs. The final chapter then presents the extensive numerical testing undertaken with the solvers proposed in the prior chapters. Some conclusions and an appendix complete the thesis

Applications of aerospace technology in the electric power industry

An overview of the electric power industry, selected NASA contributions to progress in the industry, linkages affecting the transfer and diffusion of technology, and, finally, a perspective on technology transfer issues are presented

Exploring manycore architectures for next-generation HPC systems through the MANGO approach

[EN] The Horizon 2020 MANGO project aims at exploring deeply heterogeneous accelerators for use in High-Performance Computing systems running multiple applications with different Quality of Service (QoS) levels. The main goal of the project is to exploit customization to adapt computing resources to reach the desired QoS. For this purpose, it explores different but interrelated mechanisms across the architecture and system software. In particular, in this paper we focus on the runtime resource management, the thermal management, and support provided for parallel programming, as well as introducing three applications on which the project foreground will be validated.This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 671668.Flich Cardo, J.; Agosta, G.; Ampletzer, P.; Atienza-Alonso, D.; Brandolese, C.; Cappe, E.; Cilardo, A.... (2018). Exploring manycore architectures for next-generation HPC systems through the MANGO approach. Microprocessors and Microsystems. 61:154-170. https://doi.org/10.1016/j.micpro.2018.05.011S1541706

ONE FACTOR RESPONSE SURFACE METHODOLOGY (RSM) FOR THE OPTIMIZATION OF ORAL VENLAFAXINE HCL CONTROLLED RELEASE ORGANOGEL

Objective: The aim of this study was to develop the oral Venlafaxine HCl controlled-release organogel (organogel–CR) by using one-factor response surface methodology (RSM). Methods: In this study, Drug-excipient compatibility was evaluated by FT-IR. A total of 14 experimental runs were carried out employing the detailed conditions designed by a single factor completely randomized design based on the response surface methodology was used to check the concentration effect of 12-Hydroxy stearic acid (12-HSA) at different cooling rates on drug release at 10 h (Q10) and after 12 h (Q12). Multiple linear regression analysis, analysis of variance (ANOVA) and graphical representation of the influence factor were performed by using design expert 12. The developed organogel was also evaluated for viscosity, strength, transition temperature, diffusivity and Scanning electron microscopy (SEM). Prepared organogel was filled in the capsule and investigated for weight variation, drug content, erosion of organogel and In vitro drug release study. Results: FT-IR results showed that there was no chemical interaction between the drug and excipients. The SEM photograph indicates that the developed organogel was highly viscous with 3D network structure. The experimental confirmation tests showed a correlation between the predicted and experimental responses (R2 = 0.9937 and 0.9709). The results of ANOVA suggested that calculated F values of all dependent variables are greater than tabulated values. The optimal point obtained was located in the valid region and the optimum in vitro release of the predicted batch containing 7.9% concentration of 12-HSA with gradual cooling rate. To validate the evolved mathematical models, a checkpoint was selected and its desirability value was found to be 0.866. Conclusion: Oral controlled release Venlafaxine HCl organogel fix the problem of repeated dosing and patient noncompliance