10,190 research outputs found

    Towards A Practical High-Assurance Systems Programming Language

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    Writing correct and performant low-level systems code is a notoriously demanding job, even for experienced developers. To make the matter worse, formally reasoning about their correctness properties introduces yet another level of complexity to the task. It requires considerable expertise in both systems programming and formal verification. The development can be extremely costly due to the sheer complexity of the systems and the nuances in them, if not assisted with appropriate tools that provide abstraction and automation. Cogent is designed to alleviate the burden on developers when writing and verifying systems code. It is a high-level functional language with a certifying compiler, which automatically proves the correctness of the compiled code and also provides a purely functional abstraction of the low-level program to the developer. Equational reasoning techniques can then be used to prove functional correctness properties of the program on top of this abstract semantics, which is notably less laborious than directly verifying the C code. To make Cogent a more approachable and effective tool for developing real-world systems, we further strengthen the framework by extending the core language and its ecosystem. Specifically, we enrich the language to allow users to control the memory representation of algebraic data types, while retaining the automatic proof with a data layout refinement calculus. We repurpose existing tools in a novel way and develop an intuitive foreign function interface, which provides users a seamless experience when using Cogent in conjunction with native C. We augment the Cogent ecosystem with a property-based testing framework, which helps developers better understand the impact formal verification has on their programs and enables a progressive approach to producing high-assurance systems. Finally we explore refinement type systems, which we plan to incorporate into Cogent for more expressiveness and better integration of systems programmers with the verification process

    Studying the interplay between ageing and Parkinson's disease using the zebrafish model

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    Parkinson’s disease (PD) is a neurodegenerative disorder characterised by the loss of dopaminergic neurons in the substantia nigra. Ageing is the major risk factor for developing PD but the interplay between ageing and PD remains elusive. To investigate the effect of ageing on PD-relevant pathological mechanisms, zebrafish mutant lines harbouring mutations in ageing-associated genes (klotho-/-, sirt1-/-, satb1a-/-, satb1b-/- and satb1a-/-;satb1b-/-) were generated, using CRISPR/Cas9 gene editing. Likewise, a chemical model for SIRT1 deficiency was utilised. klotho-/- zebrafish displayed an accelerated ageing phenotype at 3mpf and reduced survival to 6mpf. Dopaminergic neuron number, MPP+ susceptibility and microglial number were unaffected in klotho-/- larvae. NAD+ levels were decreased in 6mpf klotho-/- brains. However, ATP levels and DNA damage were unaffected. sirt1-/- zebrafish did not display a phenotype through adulthood. il-1β and il-6 were not upregulated in sirt1-/- larvae, and chemical inhibition of sirt1 did not increase microglial number. cdkn1a, il-1β and il-6 were not upregulated in satb1a-/- and satb1b-/- larvae. Dopaminergic neuron number and MPP+ susceptibility were unaffected in satb1a-/- larvae. However, satb1b-/- larvae demonstrated a moderate decrease in dopaminergic neuron number but equal susceptibility to MPP+ as satb1b+/+ larvae. Adult satb1a-/- but not adult satb1b-/- zebrafish were emaciated. satb1a-/-;satb1b-/- zebrafish did not display a phenotype through adulthood. Transgenic zebrafish expressing human wildtype α-Synuclein (Tg(eno2:hsa.SNCA-ires-EGFP)) were crossed with klotho-/- and sirt1-/- zebrafish, and treated with a sirt1-specific inhibitor. Neither genetic cross affected survival. The klotho mutation did not increase microglial number in Tg(eno2:hsa.SNCA-ires-EGFP) larvae. Likewise, sirt1 inhibition did not induce motor impairment or cell death in Tg(eno2:hsa.SNCA-ires-EGFP) larvae. In conclusion, the suitability of zebrafish for studying ageing remains elusive, as only 1 ageing-associated mutant line displayed accelerated ageing. However, zebrafish remain an effective model for studying PD-relevant pathological mechanisms due to the availability of CRISPR/Cas9 gene editing, neuropathological and neurobehavioral tools

    Beam scanning by liquid-crystal biasing in a modified SIW structure

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    A fixed-frequency beam-scanning 1D antenna based on Liquid Crystals (LCs) is designed for application in 2D scanning with lateral alignment. The 2D array environment imposes full decoupling of adjacent 1D antennas, which often conflicts with the LC requirement of DC biasing: the proposed design accommodates both. The LC medium is placed inside a Substrate Integrated Waveguide (SIW) modified to work as a Groove Gap Waveguide, with radiating slots etched on the upper broad wall, that radiates as a Leaky-Wave Antenna (LWA). This allows effective application of the DC bias voltage needed for tuning the LCs. At the same time, the RF field remains laterally confined, enabling the possibility to lay several antennas in parallel and achieve 2D beam scanning. The design is validated by simulation employing the actual properties of a commercial LC medium

    China-US Competition

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    This open access edited book brings together a closer examination of European and Asian responses to the escalating rivalry between the US and China. As the new Cold War has surfaced as a perceivable reality in the post-COVID era, the topic itself is of great importance to policymakers, academic researchers, and the interested public. Furthermore, this manuscript makes a valuable contribution to an under-studied and increasingly important phenomenon in international relations: the impact of the growing strategic competition between the United States and China on third parties, such as small and middle powers in the two arguably most affected regions of the world: Europe and East Asia. The European side has been under-studied and explicitly comparative work on Europe and East Asia is extremely rare. Given that the manuscript focuses heavily on recent developments—and because many of these developments have been quite dramatic—there are very few publications that cover the same topics

    Relational Approach to the L-Fuzzy Concept Analysis

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    Modern industrial production systems benefit from the classification and processing of objects and their attributes. In general, the object classification procedure can coincide with vagueness. Vagueness is a common problem in object analysis that exists at various stages of classification, including ambiguity in input data, overlapping boundaries between classes or regions, and uncertainty in defining or extracting the properties and relationships of objects. To manage the ambiguity mentioned in the classification of objects, using a framework for L-fuzzy relations, and displaying such uncertainties by it can be a solution. Obtaining the least unreliable and uncertain output associated with the original data is the main concern of this thesis. Therefore, my general approach to this research can be categorized as follows: We developed an L-Fuzzy Concept Analysis as a generalization of a regular Concept Analysis. We start our work by providing the input data. Data is stored in a table (database). The next step is the creation of the contexts and concepts from the given original data using some structures. In the next stage, rules, or patterns (Attribute Implications) from the data will be generated. This includes all rules and a minimal base of rules. All of them are using L-fuzziness due to uncertainty. This requires L-fuzzy relations that will be implemented as L -valued matrices. In the end, everything is nicely packed in a convenient application and implemented in Java programming language. Generally, our approach is done in an algebraic framework that covers both regular and L -Fuzzy FCA, simultaneously. The tables we started with are already L-valued (not crisp) in our implementation. In other words, we work with the L-Fuzzy data directly. This is the idea here. We start with vague data. In simple terms, the data is shown using L -valued tables (vague data) trying to relate objects with their attributes at the start of the implementation. Generating attribute implications from many-valued contexts by a relational theory is the purpose of this thesis, i.e, a range of degrees is used to indicate the relationship between objects and their properties. The smallest degree corresponds to the classical no and the greatest degree corresponds to the classical yes in the table

    Advances in performance and automation of a single ytterbium ion optical clock

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    While the SI second is currently defined in terms of a microwave transition frequency in caesium, atomic clocks based on an optical transition are currently outperforming caesium clocks by up to two orders of magnitude. In order to fully exploit the potential accuracy achievable by optical clocks, the SI second needs to be redefined in terms of an optical frequency standard. The ¹⁷¹Yb⁺ ion is an excellent candidate thanks to the extremely narrow linewidth of its electric octupole (E3) transition and its particular insensitivity to external perturbations. This thesis is focused on the ytterbium ion optical clock at the National Physical Laboratory (NPL), consisting of a single ¹⁷¹Yb⁺ ion trapped in a radio frequency (RF) Paul trap and probed by ultrastable 467-nm light to excite the E3 transition. Improved measurement methods were developed for the evaluation of several systematic frequency shifts. In particular, the electric quadrupole shift, which used to be the leading source of uncertainty, can now be directly measured with an accuracy in the low parts in 10¹⁸. A great focus was put on the automation of several aspects of the experiment. Because all optical clocks generally require a lot of maintenance and attention during their operation, many experimental routines were automated in order to minimise the requirement for human intervention. Furthermore, the analysis of almost all systematic shifts was automated, requiring minimal manual input so that shifts could be evaluated on the fly. Finally, a generalised framework was developed for the automatic evaluation of the absolute frequency of the optical clock via the International Atomic Time (TAI). In order to increase the confidence in the level of performance of the ytterbium ion optical clock, international clock comparison campaigns are regularly carried out. Between 2019 and 2022, several results were produced: two absolute frequency measurements via TAI with an uncertainty at the 1 × 10⁻¹⁵ level; two local frequency ratio measurements between ¹⁷¹Yb⁺ (E3) and ⁸⁷Sr with an uncertainty in the low parts in 10¹⁷; three uncertainty budgets at the parts in 10¹⁸ level; and one measurement of the ratio of the octupole and quadrupole optical clock transitions in ¹⁷¹Yb⁺ with an uncertainty of 1.5 × 10⁻¹⁶. All of these results are shown to be consistent with each other and in good agreement with the literature. Furthermore, a prototype optically-steered time scale was successfully demonstrated for the first time at NPL with the contribution of both the ¹⁷¹Yb⁺ and ⁸⁷Sr optical clocks.Open Acces

    Cryogenic silicon Fabry-Perot resonator with Al0.92Ga0.08As/GaAs mirror coatings

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    The sensitivity and stability of today's most precise optical interferometers, like gravitational wave detectors and ultra-stable lasers, are fundamentally limited by thermodynamically induced length fluctuations of high-reflectivity mirror coatings. Among them, Brownian thermal noise related to internal friction is the dominant contribution and can be reduced by using coating materials with lower mechanical loss. Owing to their low mechanical losses, AlGaAs/GaAs crystalline mirror coatings are expected to reduce this limit set by conventional dielectric coatings as demonstrated from a room temperature measurement. However, due to the high noise contributions from other resonator constituents in previous study, accurate characterization of the noise of crystalline coatings has yet been possible. In this work, the first detailed study on the spatial and temporal noise properties of crystalline coatings at an unprecedented level of precision is presented. This was achieved by using these novel coatings in a cryogenic silicon Fabry-Perot resonator operating at a temperature of 124 K and at a wavelength of 1.5 µm. To observe the expected low fractional frequency instability of mod σ_y=1x10^-17 imposed significant challenges in suppressing technical noise contributions. With methods and experimental setups described in this work, technical noise contributions were suppressed to a level well below the predicted coating noise. Nevertheless, the measured frequency was significantly higher than the predicted thermal and the total technical noise, which indicates the existence of excess noise in crystalline coatings. To disentangle the different excess noise sources, a sophisticated interrogation scheme, which investigates spatiotemporal correlations between different cavity eigenmodes by stabilizing two independent lasers simultaneously on the resonator, was developed. With this interrogation scheme, noise mechanisms related to the large birefringence mode splitting in these coatings were discovered. Upon a step change of optical power, anticorrelated frequency transient responses between the two birefringence-induced polarization eigenmodes of the silicon resonator were measured. The frequency noise induced by power fluctuations from this photo-birefringent effect was reduced to a neglectable level by active stabilization of optical power. However, anticorrelated spontaneous frequency fluctuations between the two polarization eigenmodes were still observed, indicating intrinsic birefringence fluctuations. To cancel this dominant excess noise - birefringent noise - in the crystalline coating, a dual-frequency locking technique was developed to stabilize the laser to the average of both polarization eigenmodes. With this technique, the expected low Brownian thermal noise was verified, but at the same time, this revealed another novel global excess noise with a correlation length larger than the mode diameter of 1 mm. This excess noise currently limits the frequency stability of the new cryogenic silicon resonator at a level comparable to dielectric coatings. Due to its large correlation length, increasing the beam size will only marginally reduce the noise level. In future ultra-sensitive interferometers using similar coatings based on semiconductor materials, these novel noise contributions discovered in this thesis must be carefully considered

    Metal-Organic Frameworks and Covalent Organic Frameworks as single site catalysts for organic transformations

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    Els Metal-Organic frameworks (MOFs) i Covalent Organic Frameworks (COFs) són nous tipus de materials porosos que han atret una gran atenció a causa de la seva combinació única de propietats: alta porositat, bona estabilitat química, estructures ben ordenades i gran capacitat d'ajustament estructural. Entre les seves aplicacions possibles, la catàlisi és una de les més prometedores a causa del potencial dels MOFs i COFs per formar catalitzadors de centre únic que estan ben definits i romanen accessibles en estat sòlid. En aquesta línia de recerca, aquesta tesi té com a objectiu desenvolupar i estudiar nous catalitzadors basats en MOFs i COFs per a transformacions orgàniques. El treball presentat en aquesta tesi mostra un mètode simple per immobilitzar lligands de perilè fotocatalíticament actius dins de MOF-520, cosa que permet estudiar els lligands com a unitats aïllades i emprar els MOF com a fotocatalitzadors heterogenis per a l'acoblament reductiu d'enllaços C=O i C =N. Aquesta tesi també descriu la síntesi i caracterització d'una sèrie de COFs que porten lligands donadors de N a la seva estructura. La incorporació de Co a aquestes estructures va donar com a resultat MCOFs, que es van emprar com a catalitzadors d'hidroboració i borilació. Finalment, es van fer estudis per explorar la naturalesa de centre únic dels centres catalítics. Aquest treball mostra el potencial de MOF i COF com a catalitzadors heterogenis eficients i reciclables per a transformacions orgàniques i aplana el camí per al desenvolupament de nous sistemes catalítics de centre únic.Los Metal-Organic frameworks (MOFs) y Covalent Organic Frameworks (COFs) son nuevos tipos de materiales porosos que han atraído una gran atención debido a su combinación única de propiedades: alta porosidad, buena estabilidad química, estructuras bien ordenadas y gran capacidad de ajuste estructural. Entre sus muchas aplicaciones posibles, la catálisis es una de las más prometedoras debido al potencial de MOFs y COFs para formar catalizadores de centro único que estén bien definidos y permanezcan accesibles en estado sólido. En esta línea de investigación, la presente tesis tiene como objetivo desarrollar y estudiar nuevos catalizadores basados en MOFs y COFs para transformaciones orgánicas. El trabajo presentado en esta tesis muestra un método simple para inmovilizar ligandos de perileno fotocatalíticamente activos dentro de MOF-520, lo que permite estudiar los ligandos como unidades aisladas y emplear los MOF como fotocatalizadores heterogéneos para el acoplamiento reductivo de enlaces C=O y C=N. Esta tesis también describe la síntesis y caracterización de una serie de COFs que portan ligandos donantes de N en su estructura. La incorporación de Co en estas estructuras dio como resultado MCOFs, que se emplearon como catalizadores de hidroboración y borilación. Finalmente, se realizaron estudios para explorar la naturaleza de centro único de los centros catalíticos. Este trabajo muestra el potencial de MOF y COF como catalizadores heterogéneos eficientes y reciclables para transformaciones orgánicas y allana el camino para el desarrollo de nuevos sistemas catalíticos de centro único.Metal-organic frameworks (MOFs) and Covalent Organic Frameworks (COFs) are new types of porous materials that have attracted great attention due to their unique combination of properties: high porosity, good chemical stability, well-ordered structures and great structural tuneability. Among their many possible applications, catalysis is one of the most promising due to the potential of MOFs and COFs to form single-site catalysts that are well defined and remain accessible in the solid state. In this line of research, the current thesis aims to develop and study new MOF and COF-based catalysts for organic transformations. The work presented in this thesis shows a simple method to immobilize photocatalytically active perylene ligands inside MOF-520, allowing this way to study the ligands as isolated units, and to employ the MOFs as heterogeneous photocatalysts for the reductive coupling of C=O and C=N bonds. This thesis also describes the synthesis and characterization of a series of COFs bearing N-donor ligands in their structure. Incorporation of Co into these structures resulted in MCOFs, which were employed as hydroboration and borylation catalysts. Finally, studies were performed to explore the single-site nature of the catalytic centers. This work showcases the potential of MOFs and COFs as efficient and recyclable heterogeneous catalysts for organic transformations, and paves the way for the development of new single-site catalytic systems

    Assessing the therapeutic potential of mitochondrial uncoupler BAM15

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    Our health rests on the condition of our mitochondria. One class of drugs shown to improve mitochondrial function by targeting bioenergetics are mitochondrial uncouplers. These drugs decrease the efficiency of adenosine triphosphate (ATP) production and concurrently decrease the production of reactive oxygen species (ROS). Therefore, mitochondrial uncoupling may have efficacy in treating conditions of nutrient excess such as obesity and metabolic disease, as well as conditions associated with oxidative damage such as ageing. The objective of this thesis was to assess the therapeutic potential of small molecule mitochondrial uncoupler BAM15. BAM15 was found to increase energy expenditure in a dose dependent manner, without evidence of toxicity or hyperthermia. BAM15 was subsequently tested in C57BL/6J mouse models of obesity, non-alcoholic fatty liver disease (NASH) and healthy ageing. In a western diet-induced model of obesity BAM15 was found to prevent and reverse fat accumulation and insulin resistance without altering food intake or decreasing lean body mass. Beneficial effects were observed on liver fat accumulation, inflammation, and oxidative damage. Hyperinsulinemic-euglycemic clamp studies showed that BAM15 improved insulin sensitivity in multiple tissue types. In a biopsy-confirmed Amylin diet-induced model of non-alcoholic steatohepatitis (NASH), BAM15 led to improvements in liver enzymes, steatosis, and inflammation. Finally, BAM15 was found to prevent age-related fat gain, without loss of lean mass. It was also protective against age-related loss of insulin sensitivity and loss of circadian fluctuation in respiratory exchange ratio (RER). This thesis has validated the therapeutic potential of BAM15 and laid the foundation for continued research into how targeting mitochondrial bioenergetics can improve health

    The energy security of five EU countries between 2000 and 2020 : France, Germany, Hungary, Poland, and Portugal

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    Mestrado Bolonha em Economia Internacional e Estudos EuropeusEnergy security has become a key issue for the EU, whose legislative production in the area is constantly growing. How are Member States responding to energy security challenges? This study examines the energy security evolution of five Member States between 2000 and 2020: France, Germany, Hungary, Poland and Portugal. The literature covered by the study describes a recent field that is characterized by its multidimensional aspect. The choice was made to study energy security through four dimensions (energy efficiency, affordability, availability, and environmental stewardship) which were the base of the eight indicators’ index that was developed in this work. The latter, constructed using the z-score normalization method, revealed progress for the EU as a whole but different dynamics within the five countries studied. The EU energy security trend is characterized by an improvement in the Energy Efficiency and Environmental Stewardship dimensions, but also by a deterioration in the Affordability dimension. As for the Availability dimension, the European average improved in one indicator but deteriorated in the other. On the other hand, the index showed a greater improvement in France and Portugal’s energy security compared to the EU evolution. In contrast, the energy security of Hungary, Poland and Germany improved, but to a smaller extent than the EU average. Additionally, the examination of performance in the selected indicators enabled us to identify points of weakness as well as European or national policies that have aimed to mitigate these weaknesses.info:eu-repo/semantics/publishedVersio
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