VictorJuiz/thesis huggingface dataset:
Dengue diagnostics and therapeutic interventions in Viet Nam
Keywords: Viet Nam
clinical trial
point-of-care systems
antiviral agents
dengue
neglected tropical diseases
virology
diagnostic

Dengue is a major public health problem that affects tens of millions of people annually in tropical and sub-tropical countries. This acute viral infection happens to be severe and even life threatening but there is still no available drug or vaccine. Previous studies have noted early higher viral burden in patients who develop more severe symptoms suggesting that administration of a potent and safe antiviral may prevent progression to severe dengue. To verify this hypothesis, we have conducted the first RCT directed towards reducing the viral burden in vivo by administrating chloroquine (CQ), a cheap and well-tolerated drug that inhibits DENV in vitro with concentrations achievable in vivo, to 307 Vietnamese adults with suspected dengue (257 of them were laboratory-confirmed cases). Unfortunately, we did not see an effect of CQ on the duration of infection. However in patients treated with CQ, we observed a trend towards a lower incidence of severe forms. We did not find any differences in the immune response that can explain this trend. We also found more adverse events, primarily vomiting, with CQ. In addition, we have explored the relationships between clinical features, antibody responses and virological markers in these patients. We found that the early magnitude of viremia is positively associated with disease severity and there are serotype dependent differences in infection kinetics. We found as well that DENV was cleared faster and earlier in patients with secondary infections. To complete this study, we have also evaluated 2 rapid lateral flow tests for the diagnosis of dengue in a panel of plasma samples from 245 RT-PCR confirmed dengue patients and 47 with other febrile illnesses. Our data suggest that the NS1 test component of these tests are highly specific and have similar levels of sensitivity (~60%). Both NS1 assays were significantly more sensitive for primary than secondary dengue. The IgM parameter in the SD Duo test improved overall test sensitivity without compromising specificity. All these findings are of major importance for further anti-viral drug testing.
When scientists meet the public: an investigation into citizen cyberscience
Keywords: Science and Technology Studies
citizen science
climate science
virtual ethnography
astronomy

Citizen Cyberscience Projects (CCPs) are projects mediated through the Internet, in which teams of scientists recruit members of the public (volunteers) to assist in scientific research, typically through the processing of large quantities of data. This thesis presents qualitative ethnographic case studies of the communities that have formed around two such projects, climateprediction.net and Galaxy Zoo. By considering these social actors in the broader contexts in which they are situated (historical, institutional, social, scientific), I discuss the co-shaping of the interests of these actors, the nature of the relationships amongst these actors, and the infrastructure of the projects and the purposes and nature of the scientific work performed.
The thesis focusses on two relationships in particular. The first is that between scientists and volunteers, finding that, although scientists in both projects are concerned with treating volunteers with respect, there are nevertheless considerable differences between the projects. These are related to a number of interconnecting factors, including the particular contexts in which each project is embedded, the nature of the scientific work that volunteers are asked to undertake, the possibilities and challenges for the future development of the projects as perceived by the scientists, and the tools at the disposal of the respective teams of scientists for mediating relationships with volunteers. The second is amongst the volunteers themselves. This thesis argues that volunteers are heterogeneous, from disparate backgrounds, and that they sustain their involvement in CCPs for very different purposes. In particular, they seek to pursue these through the way they negotiate and construct their relationships with other volunteers, drawing on particular features of the project to do so.
This thesis contributes to two fields. The first is to Citizen Cyberscience itself, with a view to improving the running of such projects. Some social studies have already been conducted of CCPs to this end, and this thesis both extends the analysis of some of these pre-existing studies and also problematizes aspects of CCPs that these studies had not considered. I discuss the significance of my findings for those involved in setting up and running a CCP, and present some recommendations for practice. The second field is Science and Technology Studies, in particular studies of public engagement with scientific and technological decision- and knowledge-making processes. The modes of engagement found in CCPs differ in key ways from those that have already been documented in the existing literature (in particular, different power relationships) and thus offer new ways of understanding how the public might be engaged successfully in such processes.
Molecular Rydberg dynamics
Keywords: quantum defect theory
electronic spectroscopy
Rydberg molecule

A simple theory relating the dynamics of electrons to the long-range properties of the molecular ionic core is developed for asymmetric top molecules in general and water in particular. It is combined with the molecular version of multichannel quantum defect theory developed by Fano and Jungen and applied to the resonance-enhanced multiphoton ionization spectra of Child and Glab (M. S. Child and W. G. Glab, J. Chem. Phys., 2001, 112, 3754-3765), the mass-analysed threshold ionization spectra of Dickinson et al. (H. Dickinson, S. R. Mackenzie and T. P. Softley, Phys. Chem. Chem. Phys., 2000, 2, 4669-4675) and the as-yet unpublished work of Glab on the photoelectron branching ratios of the nd and nf Rydberg lines of the water molecule. The effect of resonances between electronic and rotational motion in Rydberg molecules is investigated using multichannel quantum defect theory with special reference to the time-resolved wave packet experiments of Smith et al. (R. A. L. Smith, J. R. R. Verlet, E. D. Boleat, V. G. Stavros and H. H. Fielding, Faraday Discuss., 2000, 115, 63-70).
Static analyses over weak memory
Keywords: weak memory
concurrency
memory fence
static analysis

Writing concurrent programs with shared memory is often not trivial. Correctly synchronising the threads and handling the non-determinism of executions require a good understanding of the interleaving semantics. Yet, interleavings are not sufficient to model correctly the executions of modern, multicore processors. These executions follow rules that are weaker than those observed by the interleavings, often leading to reorderings in the sequence of updates and readings from memory; the executions are subject to a weaker memory consistency. Reorderings can produce executions that would not be observable with interleavings, and these possible executions also depend on the architecture that the processors implement. It is therefore necessary to locate and understand these reorderings in the context of a program running, or to prevent them in an automated way.
In this dissertation, we aim to automate the reasoning behind weak memory consistency and perform transformations over the code so that developers need not to consider all the specifics of the processors when writing concurrent programs. We claim that we can do automatic static analysis for axiomatically-defined weak memory models. The method that we designed also allows re-use of automated verification tools like model checkers or abstract interpreters that were not designed for weak memory consistency, by modification of the input programs.
We define an abstraction in detail that allows us to reason statically about weak memory models over programs. We locate the parts of the code where the semantics could be affected by the weak memory consistency. We then provide a method to explicitly reveal the resulting reorderings so that usual verification techniques can handle the program semantics under a weaker memory consistency. We finally provide a technique that synthesises synchronisations so that the program would behave as if only interleavings were allowed. We finally test these approaches on artificial and real software. We justify our choice of an axiomatic model with the scalability of the approach and the runtime performance of the programs modified by our method.
Intersection types and higer-order model checking
Keywords: software verification
intersection types
model checking

Higher-order recursion schemes are systems of equations that are used to define finite and infinite labelled trees. Since, as Ong has shown, the trees defined have a decidable monadic second order theory, recursion schemes have drawn the attention of research in program verification, where they sit naturally as a higher-order, functional analogue of Boolean programs. Driven by applications, fragments have been studied, algorithms developed and extensions proposed; the emerging theme is called higher-order model checking. Kobayashi has pioneered an approach to higher-order model checking using intersection types, from which many recent advances have followed. The key is a characterisation of model checking as a problem of intersection type assignment. This dissertation contributes to both the theory and practice of the intersection type approach.
A new, fixed-parameter polynomial-time decision procedure is described for the alternating trivial automaton fragment of higher-order model checking. The algorithm uses a novel, type-directed form of abstraction refinement, in which behaviours of the scheme are distinguished according to the intersection types that they inhabit. Furthermore, by using types to reason about acceptance and rejection simultaneously, the algorithm is able to converge on a solution from two sides. An implementation, Preface, and an extensive body of evidence demonstrate empirically that the algorithm scales well to schemes of several thousand rules. A comparison with other tools on benchmarks derived from current practice and the related literature puts it well beyond the state-of-the-art.
A generalisation of the intersection type approach is presented in which higher-order model checking is seen as an instance of exact abstract interpretation. Intersection type assignment is used to characterise a general class of safety checking problems, defined independently of any particular representation (such as automata) for a class of recursion schemes built over arbitrary constants. Decidability of any problem in the class is an immediate corollary. Moreover, the work looks beyond whole-program verification, the traditional territory of model checking, by giving a natural treatment of higher-type properties, which are sets of functions.
Gifts to the Gods: Aparchai, Dekatai and related offerings in Archaic and Classical Greece
Keywords: Greek Religion
aparchai
first-fruits
dekatai
tithes

This study is about one of the most ubiquitous and yet little studied aspects of ancient Greek religion, the offering of so-called ‘first-fruits’ (aparchai) and tithes (dekatai) in Archaic and Classical Greece (c.700-300 B.C.). A widespread and traditional custom all over Greece and the Greek Mediterranean, the offering of ‘first-fruits’ and tithes entailed using a portion of the proceeds from a diversity of human activities (such as craft-work, fishing, trade, military expeditions) to present something to the gods. I look at the different kinds of aparchai and dekatai offered to the Greek gods by individuals and states under various circumstances, the various contexts in which the language and practice of making such offerings were used, the deployment of this religious custom in politics, and the transformation of a voluntary practice into a religious obligation. Ultimately, however, my major concern is with questions of religious psychology: why people should bring aparchai and dekatai to the gods, and what motivations and expectations they might have had. Because it was such a commonplace practice, the custom has been taken simply as a given in both ancient and modern scholarship; and no attempt has been made to explain its religious significance. By drawing on current anthropological studies of gift-giving, I argue that that aparchai and dekatai do not merely give to the gods, but give back to the gods some of the benefits granted by the divinities in the first place, reflecting first and foremost a sense of dependence on the divine. I suggest that the offering of aparchai and dekatai may be thought of as a means of settling men’s debts to, and thereby maintaining good relations with, the gods, who were considered the sources of both goods and evils. I challenge the emphasis, common in modern scholarship, on material returns as the central motive behind the act of bringing gifts to the gods. Instead I suggest that the study of gift-giving between humans and the divine should embrace the possibility that psychological feelings of dependence on and gratitude to the gods might also have been involved.
Centring on the Margins: Migration Control in Malta, Cyprus and the European Union
Keywords: migration control
borders
migrant agency
Cyprus
power
irregular immigration
Malta
European Union
small states

Why does the European Union focus on controlling irregular immigration at the external border? The emphasis presents a paradox as most irregular migrants in the EU arrive through legal channels and subsequently overstay or violate the conditions of their visa. In order to explore this paradox, the thesis examines two case studies, Malta and Cyprus. As small island states on the Union’s southern periphery, the two are ostensibly unable to resist the transfer of migration controls and asylum responsibility to the EU’s external borders. Yet, employing nonmaterial power, namely by highlighting the perceived migration pressures they are under, the two states have successfully attracted significant financial and practical support from other member states. In doing so, they have influenced policymaking within EU migration governance, but have ultimately reinforced the emphasis on controlling irregular immigration at the external border by portraying the phenomenon as a crisis.
This thesis not only sheds light on the interaction between the EU and the two states under investigation, but combines three levels of analysis – the regional, national, and local. The crisis narrative detrimentally affects the migrant and refugee populations as it encourages the adoption of restrictive and deterrent measures rather than ensuring access to rights and long-term integration. Nevertheless, this population is not without agency. It is their individual decisions to move across national borders without state authorisation that in the aggregate both compels states into dialogue about the issue and provides the basis for the dynamic between the EU and these two member states.
Analysis of the brainstem auditory evoked potentials in neurological disease
Keywords: multiple sclerosis
neuronal oscillations
evoked potentials
click polarity
brainstem
waveform analysis
auditory

Many phenomena in the BAEP are difficult to explain on the basis of the accepted hypothesis of its origin (after Jewett, 1970). The alternative mechanism of origin to which these phenomena point is summation of oscillations. Therefore, simulation of the BAEP by a mathematical model consisting of the addition of four sine waves was tested. The model did simulate a normal BAEP as well variations in the waveform produced by reversing click polarity. This simulation gives further clues to the origin of the BAEP. The four sine waves begin simultaneously; corresponding BAEP oscillations must, therefore, originate from a single structure. These oscillations begin in less than half a millisecond after the click. This suggests that the structure from which they arise is outside the brainstem. This alternative mechanism indicates that wave latencies do not reflect nervous conduction between discrete nuclei, and interpretation of BAEP abnormality need to be reconsidered. It also implies that mathematical frequency analysis is more appropriate, but this could be applied only when these methods have been perfected. Meanwhile, through visual analysis and recognition of oscillations, abnormality can be detected and described in terms that may have physiological significance.
Synthesis and elaboration of heterocycles via palladium-catalyzed C-H functionalization
Keywords: palladium-catalysis
organic synthesis
organic
chemistry
heterocycles

Chapter 1 is a brief literature review of the most recent progress in the area of C-H functionalization via palladium catalysis. This covers the functionalization of electron deficient arenes and heterocycles with alkenyl and alkyl halides both using inter- and intra-molecular reactions. The chapter also contains an overview of recent work from the Willis group.
Chapter 2 presents the functionalization of electron deficient arenes and alkenyl bromides using palladium catalysis, as well as the use of statistical analysis software for optimizing the cross-coupling reaction.
Chapter 3 describes the cross-coupling of substituted benzoxazoles, benzothiazole and benzimidazole with a range of alkenyl iodides using palladium catalysis. The reaction can tolerate both (E) and (Z) disubstituted alkenes and tri-substituted alkenyl iodides, with retention of the double bond geometry.
Chapter 4 details the synthesis of sultams via an intramolecular C-H functionalization using palladium catalysis. The chapter covers the optimization of the starting material synthesis as well as the cross-coupling reaction. We can access the sulfonamides from cyclohexenone and were able to incorporate a large range of substitution patterns (Scheme 3).
Finally, Chapter 5 contains all the experimental details, general considerations and compound data. All the NMR spectra of novel compounds can be found in the appendix.
The lectin pathway of complement activation
Keywords: ficolins
lectin pathway
coagulation system
MASPS
complement

The complement system is an important immune system mechanism involved in both the recognition and elimination of invading pathogens. It is activated by three different pathways: The classical pathway, which relies on binding of C1, and results in the cleavage of C4 and C2 through activation of C1r and C1s; the alternative pathway that relies on the spontaneous hydrolysis of C3 and the lectin pathway. The lectin pathway is activated by binding of Mannan-binding lectin (MBL) or the ficolins (L-ficolin, H-ficolin and M-ficolin) to microbial binding motifs, and the subsequent activation of the MBL-associated serine proteases (MASP) 1/ 2/ 3. Of these MASP2 has been identified as the enzyme responsible for the activation of complement by C4 and C2 cleavage. The work presented here will focus on four different aspects of the lectin pathway: specificity and stoichiometry of the L-ficolin protein complex, expression of H-ficolin, substrate characterization for MASP1 and investigation of the prothrombin activation potential of MASP2. L-ficolin binding specificity was investigated using glycan array technology, and it was found that L-ficolin, instead of recognizing single monosaccharides like MBL, instead binds to extended oligosaccharide structures. The binding to these was dependent not only on the presence of acetyl groups, but also on their orientation in space. It was also found that L-ficolin in serum is found as a multimeric protein complex composed of 18 polypeptide chains and associated with one MASP dimer. The expression of H-ficolin resulted in the generation of a stable mammalian cell line producing oligomerized and biologically functional H-ficolin. MASP1 substrate specificity was investigated by two different procedures. Firstly fractionated plasma was subjected to MASP1 treatment in an attempt to identify a plasma protein substrate. This did not yield any substrate candidates, since only cleavage of the protease inhibitor α-2-macroglobulin could be detected. Additionally the thrombin-like activity of MASP1 was investigated through cleavage experiments done with factor XIII and fibrinogen. These experiments showed that the factor XIII cleavage site for MASP1 and thrombin is identical. This was also found for the fibrinogen β-chain but not for the α-chain showing that MASP1 interaction with fibrinogen is distinct from that of thrombin. An earlier observation that MASP2 was capable of activating prothrombin and generating thrombin was further characterized. Here it was shown that the activation of prothrombin by MASP2 is identical to that by factor Xa, which is the enzyme undertaking this role in the coagulation system, and that the activation can result in deposition of fibrin on the surface upon which MASP2 is bound. The prothrombin activation potential of MASP2 was also utilized to develop a new MASP2 activity assay, which was shown to be capable of measuring MASP2 activity, when MASP2 is bound, via MBL (or L-ficolin) to appropriate surfaces.
Investigating the viability of motoric task performance as a clinical biomarker in Huntington’s and Parkinson’s disease
Keywords: Parkinson's disease
clinical neurology
Huntington's disease
technology in medicine
hand tapping
Android
neuroscience

Evaluating hand tapping as a clinical biomarker in Parkinson and Huntington’s diseases, using an Android device was the objective of the study. A novel hand -tapping tool using an Android OS was developed over a year, which included 5 tapping tasks. The application was meant for installation on Samsung Galaxy 7” tablet devices. The tasks included finger tapping; metronome based tapping, simple and choice reaction time and was used to study a cross section of 45 controls of three different age groups, from 20-30 years, 35 -45 years and 65-80 years. Age and gender matched controls to Parkinson’s subjects (n=21) and Huntington’s disease patients (n=17) were assessed using the same tapping tasks. Baseline values for various tapping measures such as tapping rate, inter-tap interval, force, pro-tap (simple) reaction time, anti-tap(choice) reaction time were obtained. The study reported a significant difference between 20-30 year olds and 65-80 year olds in tapping rates and inter-tap-interval of the double target tapping task. Displacement, pro-tap time and anti-tap times were lower in 20-30s and 35-45 year olds compared to the 65-80s group. PD patients showed markedly lower values and were significantly different from controls in tapping rates, displacement of single target tapping, tapping rates and inter-tap-interval of double target tapping, pro-tap and anti-tap times and their standard deviation. HD patients had significantly lower values in inter-tap-intervals, displacement of single finger tapping, tapping rates, inter-tap interval and displacement of double target tapping, pro-tap and anti-tap reaction times. In conclusion, the study enabled us to identify tapping parameters and reaction time tests which have the potential to differentiate between Parkinson’s and Huntington’s patients with controls, therefore making motoric task performance a potentially viable clinical biomarker in HD and PD.