A theory of structural model validity in simulation.

During the last decennia, the practice of simulation has become increasingly popular among many system analysts, model builders and general scientists for the purpose of studying complex systems that surpass the operability of analytical solution techniques. As a consequence of the pragmatic orientation of simulation, a vital stage for a successful application is the issue of validating a constructed simulation model. Employing the model as an effective instrument for assessing the benefit of structural changes or for predicting future observations makes validation an essential part of any productive simulation study. The diversity of the employment field of simulation however brings about that there exists an irrefutable level of ambiguity concerning the principal subject of this validation process. Further, the literature has come up with a plethora of ad hoc validation techniques that have mostly been inherited from standard statistical analysis. It lies within the aim of this paper to reflect on the issue of validation in simulation and to present the reader with a topological parallelism of the classical philosophical polarity of objectivism versus relativism. First, we will position validation in relation to verification and accreditation and elaborate on the prime actors in validation, i.e. a conceptual model, a formal model and behaviour. Next, we will formally derive a topological interpretation of structural validation for both objectivists and relativists. As will be seen, recent advances in the domain of fuzzy topology allow for a valuable metaphor of a relativistic attitude towards modelling and structural validation. Finally, we will discuss several general types of modelling errors that may occur and examine their repercussion on the natural topological spaces of objectivists and relativists. We end this paper with a formal, topological oriented definition of structural model validity for both objectivists and relativists. The paper is concluded with summarising the most important findings and giving a direction for future research.Model; Simulation; Theory; Scientists; Processes; Statistical analysis;

Putting the Semantics into Semantic Versioning

The long-standing aspiration for software reuse has made astonishing strides in the past few years. Many modern software development ecosystems now come with rich sets of publicly-available components contributed by the community. Downstream developers can leverage these upstream components, boosting their productivity. However, components evolve at their own pace. This imposes obligations on and yields benefits for downstream developers, especially since changes can be breaking, requiring additional downstream work to adapt to. Upgrading too late leaves downstream vulnerable to security issues and missing out on useful improvements; upgrading too early results in excess work. Semantic versioning has been proposed as an elegant mechanism to communicate levels of compatibility, enabling downstream developers to automate dependency upgrades. While it is questionable whether a version number can adequately characterize version compatibility in general, we argue that developers would greatly benefit from tools such as semantic version calculators to help them upgrade safely. The time is now for the research community to develop such tools: large component ecosystems exist and are accessible, component interactions have become observable through automated builds, and recent advances in program analysis make the development of relevant tools feasible. In particular, contracts (both traditional and lightweight) are a promising input to semantic versioning calculators, which can suggest whether an upgrade is likely to be safe.Comment: to be published as Onward! Essays 202

Streptococci in an Aboriginal Australian Community: Is there a link between dogs and humans?

Dogs are an important part of modern Aboriginal Australian life in their role as hunters, companions and spiritual protectors. People in Aboriginal communities want their dogs to be healthy and therefore dog health programs that treat dogs and assist people to care for their dogs are popular. In the Yarrabah Aboriginal community, dogs are known to carry a number of zoonotic micro-organisms with the potential to cause disease in humans. A combination of the unhealthy appearance of free roaming dogs and lack of veterinary services has resulted in community concerns about the transmission of zoonoses. The community needs accurate information relevant to their local situation in order to develop strategies to manage canine zoonoses. This thesis is a small attempt to provide evidence about one group of bacteria with zoonotic potential, streptococci. This study was conducted in the Yarrabah Aboriginal community of far north Queensland. In other Aboriginal Australian communities dogs have been previously found to carry streptococci. In Aboriginal populations, streptococcal disease causes significant morbidity and mortality associated with invasive infections, poststreptococcal glomerulonephritis and rheumatic fever, all of which are overrepresented in the Aboriginal population. The shared environment of dogs and people in many Aboriginal communities has led to the hypothesis that dogs in these communities are reservoirs for some species of streptococci capable of causing disease in humans. This thesis had four aims: (1) Isolate streptococci from dogs and characterise the strains; (2) Investigate associations between health and social parameters of dogs and isolation of streptococci; (3) Isolate streptococci from children with skin sores and determine if there was any indication of the strains being shared with dogs; (4) Translate scientific knowledge, including the new information from this study into community action to improve the health of dogs

Direction of Arrival Method for L-Shaped Array with RF Switch : An Embedded Implementation Perspective

This paper addresses the challenge of implementing Direction of Arrival (DOA) methods for indoor localization using Internet of Things (IoT) devices, particularly with the recent direction- finding capability of Bluetooth. DOA methods are complex numerical methods that require significant computational resources and can quickly deplete the batteries of small embedded systems typically found in IoT networks. To address this challenge, the paper presents a novel Unitary R-D Root MUSIC for L-shaped arrays that is tailor-made for such devices utilizing a switching protocol defined by Bluetooth. The solution exploits the radio communication system design to speed up execution, and its root-finding method circumvents complex arithmetic despite being used for complex polynomials. The paper carries out experiments on energy consumption, memory footprint, accuracy, and execution time in a commercial constrained embedded IoT device series without operating systems and software layers to prove the viability of the implemented solution. The results demonstrate that the solution achieves good accuracy and attains an execution time of a few milliseconds, making it a viable solution for DOA implementation in IoT devices.Peer reviewe

Discovery of novel macrocyclic peptide inhibitors of CD59 through chemical biology

Immunotherapy has emerged as one of the most promising therapeutic strategies for various cancers, with several monoclonal antibodies (mAbs) having reached clinical trials or receiving FDA approval. mAbs function through several mechanisms of action, including complement dependent cytotoxicity (CdC). CdC activates the terminal pathway of the complement system to form membrane attack complex (MAC) pores on the tumour cell membrane, resulting in lysis. However, resistance or unresponsiveness to treatment remain serious barriers to full therapeutic benefit. One of the most prominent mechanisms of evasion is through overexpression of membrane bound complement regulatory proteins on the tumour cell surface, in particular CD59. Inhibitors of CD59 function therefore offer a promising therapeutic avenue to enhance the efficacy of mAb cancer therapies. Streptococcus intermedius intermedilysin (ILY) is a bacterial pore forming toxin which hijacks CD59 binding to promote pore formation on host cell membranes. The recombinant domain 4 of ILY, rILYd4, has been proposed as an inhibitor of CD59 function, however its therapeutic potential is limited by immunogenicity and poor metabolic stability. Using a co crystal structure of the ILY CD59 complex, cyclic peptides were developed based on the primary binding interface of these two proteins. Strategies to improve membrane anchoring and beta-hairpin characteristics were therefore developed with the aim of improving efficacy. Further, state of the art techniques to screen DNA encoded libraries of more than one trillion unique peptide sequences have emerged as highly powerful methodologies in ligand discovery. Two such screens, phage display and mRNA display, were therefore undertaken to identify novel cyclic peptide binders of CD59. Whilst the output of the phage display screen is yet to be fully determined, the mRNA display screen successfully identified a panel of high affinity cyclic peptide binders of CD59. One of the most promising peptides, mRNA 06, was identified with a KD of 11 nM and the co crystal structure was solved in complex with CD59. Structural studies provide unprecedented insight into the key binding residues and conformational characteristics of this peptide. In addition, functional studies show that mRNA 06 competes with ILY, and consequently rILYd4, for CD59 binding. Inhibition of CD59 represents an attractive and tractable strategy to reactivate the CdC effect of cancer therapeutic mAbs. The chemical tools and methodology developed here provides a major advance in targeting of CD59 with cyclic peptides, providing a road map for future studies. mRNA 06 represents the best performing CD59 binder identified thus far, displaying genuine promise for optimisation as an adjuvant for mAb therapy.Open Acces

Cambridge Analytica and the Public Sphere: An Investigation of Political Manipulation in the Digital Age

The Cambridge Analytica scandal, which unfolded in 2018, was a wake-up call for many and is a good illustration of political and civic consequences of big data in the digital age. In this thesis, I used theory-driven qualitative content analysis to explore political manipulation in the digital age, illustrated by the Cambridge Analytica scandal, and focus on how the democratic challenges, impugn the role of democratic citizens in the public sphere. For this matter I have used Habermas concepts of deliberative democracy, the public sphere, and citizen sovereignty extensively as a lens through which I analyse the events of 2018 and its aftermath. I was able to identify five challenges to the concept of the public sphere as it stands, and I relate my findings to how they may be consequential to the democratic system in general under a neoliberal capitalist order

Functional foods for added value

In this study innovation involves the development of a new product category; i.e. new products, new processes and new business. The development process is conveyed in narratives where a radically new product group, functional foods, is developed. These high-tech food products are associated with added value for the food business as well as for individuals and society at large. In the past decades Swedish food companies have faced an increasing competition. With increased competitive pressures, low prices and large volumes may not suffice as strategic advantage in a long-term perspective. One way of gaining competitive advantages requires finding new ways of creating added value based on technological development. It is a technological upgrading process that encompasses developing and making use of new knowledge. It may lead to the production of value added products, profits from licensing agreements and a boost for the company image. Businesses that want to succeed in this market need to develop new managerial methods, in particular in identifying critical technologies. This refers to building internal skills, employing innovative external sourcing, developing new markets with strong brands, establishing alliances, developing packaging, and finding venture capital for new developments. The strategic options also include strategies of communication. In the studied cases several factors have contributed to the successful innovation process. They are discussed in a creative management perspective, allowing for a creative perspective to be gradually complemented with a strategic planning perspective, as the innovation process proceeds. The early phases of the innovation process are characterized by an open-mindedness, flexibility and tolerance of ambiguity. The research procedures as well as the collaboration partners are changed several times during the innovation process. The later phases of the innovation process, however, are characterized by a more formal analysis seen through a strategic planning perspective. This part of the process appears more focused and communicable. In the cases this is conveyed as organizational arrangements, administrative routines for collaboration, and in different marketing strategies

Deposition and Characterization of Wide Band Gap P-Type Metal Oxides for Photovoltaic Applications

Daily, the population in the world is increasing, along with the quantity of needed energy. However, the fossils are running out and climate change is a global concern now, thus, the demand for alternative energies is growing. Solar energy comes free by the sun light and, if well harvested, it could be a valuable and readily available alternative source of energy for humanity. In this work, we perform deposition and characterization of thin films of copper oxides to be used in photovoltaic devices. Thin films of copper oxide were grown by radio frequency-magnetron sputtering in an oxygen-argon environment onto silicon and FTO-coated substrates at two different oxygen partial pressures (15% and 23%). Control over the oxygen flow during deposition is of paramount importance and quite difficult, making reproducible growth challenging. Post deposition annealing in vacuum environment was conducted on the films at different temperatures (between 250°C and 550°C), as an alternative pathway towards the creation of the desired phase and stoichiometry of copper oxide films in a reproducible manner. We investigated the surface morphology of the thin films by Scanning Electron Microscopy, Energy Dispersive X-ray, Atomic Force Microscopy and Kelvin Probe Force Microscopy. These studies show that the pristine films are made up of densely packed grains that are homogeneously distributed. In the annealed thin films, the size of the grains evolves greatly with the annealing temperature increase: besides the change in the morphology of the grains, which become bigger and less homogeneous, the films become nano porous in the annealed samples. The contact potential difference measurements show the presence of some islands in samples annealed at temperature higher than 450°C, only above this temperature, that the regions with higher and lower CPD values correlated with higher and lower work functions, respectively. Suspecting that these areas represent the co-existence of CuO and Cu2O crystals. The structural properties of the thin films were studied via spectroscopy and X-ray diffraction and Raman, which reveal that two oxide phases (i.e. CuO and Cu2O) co-exist in the films deposited with high oxygen ratio. In particular, high oxygen pressure during deposition favours CuO and annealing in vacuum converts CuO to Cu2O. Instead, low oxygen pressure II directly promotes the formation of Cu2O thin films. In the thin films deposited on glass, we also performed transmission measurements and found that the transmittance of films is higher in the near IR region while absorption is higher at the ultraviolet to visible region of the spectra. Finally, we uncovered a novel parasitic crystallite growth as a result of aging on the pristine and low-temperature annealed samples, and we found out that high temperature annealing prevents this kind of aging. This aging effect is completely absent in the thin films deposited onto the FTO substrates. Our results demonstrate the impact of the annealing mediation route in the reproducibility of Cu2O thin films, which should be explored towards the standardization of copper oxides formation technique. The produced thin films are good substrates for the deposition of Ga2O3 for dye sensitized solar cells