A Theory of Interface Modeling of Component-Based Software

Abstract, rCOS Automata-based Model of Components, Trace-based Model of Components Coordination, Conclusion and Futur Wor

ANTIMONY SPECIATION BY CHROMATOGRAPHIC SAMPLE INTRODUCTION TO PLASMA SPECTROSCOPY

Antimony (Sb), an element in Group V of the Periodic Table, has an ancient and varied chemistry with many applications in industry and medicine. However, although sensitive analytical methods exist for the determination of Sb very tittle is known about the speciation of the element. It is widely known that the toxicity of Sb is not only dependent upon its oxidation state but also its molecular form. Thus this study has utilised chromatographic sample introduction directly coupled to plasma spectroscopic instruments to facilitate separations of Sb based upon molecular form coupled with sensitive detection methods. Fundamental studies, using NMR to investigate physical changes in ligands and ESI-MS to investigate molecular ions, have shown that complexes of Sb(V) can form with compounds that might exist in biological/environmental systems, such as a-hydroxyacids. These complexes have been separated using ion-exchange and reversed-phase chromatography for the first time. A fundamental investigation of the nebuliser/spray chamber assembly was carried out in terms of the effect on the quality of the chromatographic separations. It was found that the resolution was strongly dependent upon choice of nebuliser and spraychamber. Five nebulisers and two spray-chambers were studied with the Burgener nebuliser/cyclonic spray-chamber pairing being the most useful analytically. The methods developed from these fundamental studies were applied to environmental water, plant and sediment sample extracts as well as industrial polymer leachates. These studies have shown that Sb(V) was the favoured form in terrestrial water samples, agreeing with thermodynamic assumptions. However, more unidentified Sb species were detected in sediment and plant (liverwort, moss) extracts. Hydride generation (HG) apparatus placed in-line between the HPLC and the plasma instrument facilitated analysis of reducible species and it was found that for many samples not all the Sb was in a reducible form. This was confirmed by comparison with chromatograms for analysis without HG. Sample spiking experiments showed that dissolved complexing agents from the samples would produce striking differences in chromatograms, i.e. in one case all peaks would respond to the spike whereas in another sample only one peak would respond. This was a novel discovery in this field of speciation and has highlighted possible new chemistries for trace levels of environmental Sb. This indicated the need for further studies of the complex nature of Sb in trace and ultra-trace levels in the environment leading to the production of specific reference materials. Investigation of industrial samples showed that significant work is still required especially in the area of the chromatographic elution of Sb(IlI) species from columns packed with a high percentage of aromatic organic material.Engineering & Physical Sciences Research Council; and ICI Technology Wilton Middlesborough Teessid

Scaling Distributed Ledgers and Privacy-Preserving Applications

This thesis proposes techniques aiming to make blockchain technologies and smart contract platforms practical by improving their scalability, latency, and privacy. This thesis starts by presenting the design and implementation of Chainspace, a distributed ledger that supports user defined smart contracts and execute user-supplied transactions on their objects. The correct execution of smart contract transactions is publicly verifiable. Chainspace is scalable by sharding state; it is secure against subsets of nodes trying to compromise its integrity or availability properties through Byzantine Fault Tolerance (BFT). This thesis also introduces a family of replay attacks against sharded distributed ledgers targeting cross-shard consensus protocols; they allow an attacker, with network access only, to double-spend resources with minimal efforts. We then build Byzcuit, a new cross-shard consensus protocol that is immune to those attacks and that is tailored to run at the heart of Chainspace. Next, we propose FastPay, a high-integrity settlement system for pre-funded payments that can be used as a financial side-infrastructure for Chainspace to support low-latency retail payments. This settlement system is based on Byzantine Consistent Broadcast as its core primitive, foregoing the expenses of full atomic commit channels (consensus). The resulting system has extremely low-latency for both confirmation and payment finality. Finally, this thesis proposes Coconut, a selective disclosure credential scheme supporting distributed threshold issuance, public and private attributes, re-randomization, and multiple unlinkable selective attribute revelations. It ensures authenticity and availability even when a subset of credential issuing authorities are malicious or offline, and natively integrates with Chainspace to enable a number of scalable privacy-preserving applications

Improving security and efficiency of mix-based anonymous communication systems

The communication layer leaks important private information even in the presence of encryption, which makes anonymous communication a fundamental element of systems that protect the privacy of users. Traffic mixers have long been used to achieve communication anonymity, but the security challenges and the resulted inefficiencies hinder the path to a wide adoption of these systems. In this thesis, we take a step towards improving the security of traffic mixers and building a platform for efficient anonymous communication. We begin by revisiting Binomial Mix, which is one of the most effective designs for traffic mixing proposed to date, and the one that introduced randomness to the behaviour of traffic mixers. When thoroughly examined in different traffic conditions, Binomial Mix proved to be significantly more resilient against attacks than previously believed. We then build on the design of Binomial Mix and propose two new designs for traffic mixers. The first design, Multi-Binomial Shared-Pool Mix (MBSP Mix), employs multiple sources of randomness which results in a behaviour less predictable by the attacker and thus provides a higher degree of anonymity. The second design, Multi-Binomial Independent-Pool Mix (MBIP Mix), enables a single traffic mixer to anonymise multiple communication channels with potentially differing latencies. This additional property significantly improves the security and efficiency of the mix. Moving beyond the design of traffic mixers in isolation, we propose the architecture and details of a generic framework for anonymous communication. The proposed framework consists of various parts designed to enable the integration of various Anonymous Communication Systems as plug-in components into a shared and unified system. In addition to achieving a larger user-base and enjoying its associated security benefits, this approach enables the reusability of components across multiple communication systems. Finally, we also present techniques to make the circuit establishment facility of the framework resistant towards Denial-of-Service attacks. We believe that our work is one step towards building a fully developed generic framework for anonymous communication and our results can inspire and be used for the design of a robust generic framework

Advanced Systems for Skin Delivery of Cyanocobalamin: A Model Molecule for > 1 kDa Drugs

La optimización de la biodisponibilidad de los fármacos brinda una segunda oportunidad a los fármacos que, por diversas razones, no pueden ejercer un efecto terapéutico óptimo. La piel se ha utilizado como plataforma para administrar medicamentos desde la antigüedad y, en la actualidad, se sigue considerando como una de las principales alternativas a la vía oral. Sin embargo, como interfaz entre el organismo y el medio ambiente externo, la capa más externa de la piel (estrato córneo) impide la entrada de sustancias. Esta oposición es de gran importancia para las moléculas de gran tamaño, considerando 500 Da como el tamaño máximo para que una molécula difunda de forma natural a través de la piel. La reformulación de medicamentos en forma de sistemas avanzados de administración de medicamentos (SAAM) suele ser necesaria para eludir la barrera del estrato córneo y producir un efecto terapéutico optimizado. El objetivo principal de esta tesis fue desarrollar diferentes SAAM que permitieran la difusión de moléculas grandes a través de la piel. Como molécula modelo se seleccionó la cianocobalamina (vitamina B12), que debido a su alto peso molecular (1355 Da) e hidrofobicidad, presenta una baja absorción transdérmica. Para mejorar dicha absorción y aumentar su permeabilidad a través de la piel, se utilizaron como recursos tecnológicos las vesículas lipídicas y microagujas poliméricas. De entre todos los tipos de vesículas, se eligieron concretamente los liposomas, transfersomas y etosomas convencionales y se caracterizaron haciendo especial énfasis en aquellas propiedades predictivas de una difusión y absorción mejoradas. Específicamente, los transfersomas y los etosomas mostraron las mejores características, ya que produjeron poblaciones de vesículas homogéneas de pequeño tamaño (< 200 nm) y estructuras flexibles. La liofilización se empleó para resolver los problemas de estabilidad a largo plazo que suelen afectar a este tipo de formulaciones y como un paso intermedio que permite su incorporación en un sistema de administración alternativo, concretamente las microagujas solubles. Los estudios in vitro y ex vivo confirmaron el aumento en la absorción del fármaco cuando se incorporó cianocobalamina en los SAAM en comparación con una disolución acuosa estándar. Como consecuencia de su diseño, las microagujas pudieron administrar el fármaco por vía transdérmica después de un período de latencia moderado, lo que sugiere su idoneidad para usarse como una alternativa a la administración parenteral. Alternativamente, las vesículas de lipídicas, que mostraron tiempos de latencia más prolongados para lograr concentraciones de fármaco cuantificables en la dermis, pudieron localizar la administración del fármaco en las capas externas de la piel mejorando significativamente la penetración de cianocobalamina en comparación con la solución estándar. El comportamiento neutralizador del óxido nítrico que presenta la cianocobalamina hace que sea posible tratar los trastornos inflamatorios de la piel como la dermatitis atópica o el eccema cuando se aplica tópicamente. La idoneidad y efectividad de las vesículas lipídicas para tratamientos tópicos se evaluó mediante un modelo de hipersensibilidad de tipo retardado in vivo. Los transfersomas cargados con cianocobalamina redujeron significativamente el aumento del grosor de la oreja habitual en procesos inflamatorios cutáneos, en comparación con el grupo no tratado, demostrando su eficacia. Además, los hallazgos histológicos como la reducción de la hiperplasia epidérmica, engrosamiento de la dermis y la infiltración de leucocitos confirmaron el efecto restaurador que las vesículas lipídicas de cianocobalamina pueden ejercer en la piel afectada por las patologías de carácter inmuno-inflamatorio.The bioavailability optimization of drugs provides a second opportunity to drugs, which for several reasons, cannot exert an optimal therapeutic effect. The skin has been used as a platform to deliver drugs since ancient times. Nowadays, it is still considered as one of the main alternatives to the oral route. However, as an interface between the body and the environments, the outer skin layer (stratum corneum) prevents the entrance of substances. This opposition is of major importance for large molecules, and 500 Da is consider de maximum size diffuse through the skin structure naturally. Re-formulation of drugs in advanced drug delivery systems (ADDS) is commonly needed to bypass the stratum corneum barrier and produce an optimised therapeutic effect. The main objective of this thesis was to develop different ADDS that allowed the diffusion of large molecules through the skin. As a model molecule, cyanocobalamin (vitamin B12) was selected, due to its high molecular weight (1355 Da) and hydrophobicity, what hinders its transdermal absorption. For this, lipid vesicles and polymeric microneedles were used to encapsulate and increase cyanocobalamin permeability though the skin. Among all the lipid vesicles developed over the years, conventional liposomes, transfersomes and ethosomes were chosen and characterised towards those properties predictive of an enhanced diffusion. Specifically, transfersomes and ethosomes showed the best features, as they were homogeneous populations of small size (< 200 nm) and flexible structures. Freeze-drying was used to solve the long-term stability issues that usually affect lipid vesicles, and as an intermediate step that allows their incorporation in an alternative delivery system, the dissolving microneedles. In vitro and ex vivo studies confirmed the increase in drug absorption when cyanocobalamin was incorporated in the ADDS when compared to a standard aqueous solution. As consequence of their conception, microneedles were able to deliver transdermally the drug after a moderate period, suggesting their suitability to be used as an alternative to parenteral administration. Lipid vesicles, which showed longer latency times to achieve quantifiable dermal concentrations of drug, were able to localize the drug delivery in the outer skin layers improving the penetration in comparison to the standard solution. Cyanocobalamin nitric oxide scavenger behaviour makes possible to ameliorate skin inflammatory disorders such as atopic dermatitis or eczema when applied topically. The feasibility of lipid vesicles for topical treatments was assessed by in vivo delayed-type hypersensitivity model. Cyanocobalamin-loaded transfersomes significantly reduced the increase in ear thickness in comparison to the untreated group, proving their effectiveness. In addition, histological findings such as reduced epidermal hyperplasia, dermis thicken, and leukocyte infiltration confirmed the skin restoring effect of transfersomes

Unblockable Compositions of Software Components

We present a new automata-based interface model describ-ing the interaction behavior of software components. Con-trary to earlier component- or interface-based approaches, the composition of components in our model guarantees that no behavior of one component can be blocked by the other component, independent of the actual implementation of the component as long as the interface description is respected. To this end, we develop an algorithm to compute the un-blockable interaction behavior, called the interface model of a component, from its execution model. Based on this model, we introduce composition and coordination opera-tors for the components, and we prove important composi-tionality results, showing the conditions under which com-position of interface models preserves unblockable sequences of provided services. 1