Control of the innate immune response by the mevalonate pathway.

Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-translational modification that is catalyzed by protein geranylgeranyl transferase I (GGTase I). Pyrin is an innate immune sensor that forms an active inflammasome in response to bacterial toxins. Mutations in MEFV (encoding human PYRIN) result in autoinflammatory familial Mediterranean fever syndrome. We found that protein geranylgeranylation enabled Toll-like receptor (TLR)-induced activation of phosphatidylinositol-3-OH kinase (PI(3)K) by promoting the interaction between the small GTPase Kras and the PI(3)K catalytic subunit p110δ. Macrophages that were deficient in GGTase I or p110δ exhibited constitutive release of interleukin 1β that was dependent on MEFV but independent of the NLRP3, AIM2 and NLRC4 inflammasomes. In the absence of protein geranylgeranylation, compromised PI(3)K activity allows an unchecked TLR-induced inflammatory responses and constitutive activation of the Pyrin inflammasome.

Moduli Space of (0,2) Conformal Field Theories

In this thesis we study aspects of (0,2) superconformal field theories (SCFTs), which are suitable for compactification of the heterotic string. In the first part, we study a class of (2,2) SCFTs obtained by fibering a Landau-Ginzburg (LG) orbifold CFT over a compact K\"ahler base manifold. While such models are naturally obtained as phases in a gauged linear sigma model (GLSM), our construction is independent of such an embedding. We discuss the general properties of such theories and present a technique to study the massless spectrum of the associated heterotic compactification. We test the validity of our method by applying it to hybrid phases of GLSMs and comparing spectra among the phases. In the second part, we turn to the study of the role of accidental symmetries in two-dimensional (0,2) SCFTs obtained by RG flow from (0,2) LG theories. These accidental symmetries are ubiquitous, and, unlike in the case of (2,2) theories, their identification is key to correctly identifying the IR fixed point and its properties. We develop a number of tools that help to identify such accidental symmetries in the context of (0,2) LG models and provide a conjecture for a toric structure of the SCFT moduli space in a large class of models. In the final part, we study the stability of heterotic compactifications described by (0,2) GLSMs with respect to worldsheet instanton corrections to the space-time superpotential following the work of Beasley and Witten. We show that generic models elude the vanishing theorem proved there, and may not determine supersymmetric heterotic vacua. We then construct a subclass of GLSMs for which a vanishing theorem holds.

(Table 1) Age control and temporal resolution of paleoceanographic records of the North Atlantic

Short-term changes in sea surface conditions controlling the thermohaline circulation in the northern North Atlantic are expected to be especially efficient in perturbing global climate stability. Here we assess past variability of sea surface temperature (SST) in the northeast Atlantic and Norwegian Sea during Marine Isotope Stage (MIS) 2 and, in particular, during the Last Glacial Maximum (LGM). Five high-resolution SST records were established on a meridional transect (53°N-72°N) to trace centennial-scale oscillations in SST and sea-ice cover. We used three independent computational techniques (SIMMAX modern analogue technique, Artificial Neural Networks (ANN), and Revised Analog Method (RAM)) to reconstruct SST from planktonic foraminifer census counts. SIMMAX and ANN reproduced short-term SST oscillations of similar magnitude and absolute levels, while RAM, owing to a restrictive analog selection, appears less suitable for reconstructing "cold end" SST. The SIMMAX and ANN SST reconstructions support the existence of a weak paleo-Norwegian Current during Dansgaard-Oeschger (DO) interstadials number 4, 3, 2, and 1. During the LGM, two warm incursions of 7°C water to occurred in the northern North Atlantic but ended north of the Iceland Faroe Ridge. A rough numerical estimate shows that the near-surface poleward heat transfer from 53° across the Iceland-Faroe Ridge up to to 72° N dropped to less than 60% of the modern value during DO interstadials and to almost zero during DO stadials. Summer sea ice was generally confined to the area north of 70°N and only rarely expanded southward along the margins of continental ice sheets. Internal LGM variability of North Atlantic (>40°N) SST in the GLAMAP 2000 compilation (Sarnthein et al., 2003, doi:10.1029/2002PA000771; Pflaumann et al., 2003, doi:10.1029/2002PA000774) indicates maximum instability in the glacial subpolar gyre and at the Iberian Margin, while in the Nordic Seas, SST was continuously low.

BIDIRECTIONAL AC-DC CONVERTERS USING ONE CYCLE CONTROL (OCC) FOR ELECTRIC VEHICLES

The electric vehicle (EV) market has seen a rapid growth in the recent past. With an increase in the number of electric vehicles on road, there is an increase in the number of high capacity battery banks interfacing the grid. The battery bank of an EV, besides being the fuel tank, is also a huge energy storage unit. Presently, it is used only when the vehicle is being driven and remains idle for rest of the time, rendering it underutilized. Whereas on the other hand, there is a need of large energy storage units in the grid to filter out the fluctuations of supply and demand during a day. EVs can help bridge this gap. The EV battery bank can be used to store the excess energy from the grid to vehicle (G2V) or supply stored energy from the vehicle to grid (V2G ), when required. To let power flow happen, in both directions, a bidirectional AC-DC converter is required. This thesis concentrates on the bidirectional AC-DC converters which have a control on power flow in all four quadrants for the application of EV battery interfacing with the grid. This thesis presents a bidirectional interleaved full bridge converter topology. This helps in increasing the power processing and current handling capability of the converter which makes it suitable for the purpose of EVs. Further, the benefit of using the interleaved topology is that it increases the power density of the converter. This ensures optimization of space usage with the same power handling capacity. The proposed interleaved converter consists of two full bridges. The corresponding gate pulses of each switch, in one cell, are phase shifted by 180 degrees from those of the other cell. The proposed converter control is based on the one-cycle controller. To meet the challenge of new requirements of reactive power handling capabilities for grid connected converters, posed by the utilities, the controller is modified to make it suitable to process the reactive power. A fictitious current derived from the grid voltage is introduced in the controller, which controls the converter performance. The current references are generated using the second order generalized integrators (SOGI) and phase locked loop (PLL). A digital implementation of the proposed control ii scheme is developed and implemented using DSP hardware. The simulated and experimental results, based on the converter topology and control technique discussed here, are presented to show the performance of the proposed theory.

International Sales of UK Television Content: Change and Continuity in ‘the space in between’ Production and Consumption

Focusing on the UK, this article addresses key issues facing the international distribution industry arising from over-the-top digital distribution and the fragmentation of audiences and revenues. Building on the identification of these issues, it investigates the extent to which UK distribution has altered over a ten-year period, pinpointing continuities in the destination and type of sales alongside changes in the role and structure of the industry as UK-based distributors adapt to a changing UK broadcasting landscape and global production environment. At one level increasing US ownership of UK-based distributors and the arrival of OTT players like Netflix, highlight the tensions between the national orientations of UK broadcasters and the global aspirations of independent producers and distributors. At another level VOD has boosted international sales of UK drama. Although the full impact of SVOD on content and rights has yet to materialise, significant changes in the industry predate the arrival of SVOD.

Colonialism, political unconscious and cognitive mapping in the space of the film "Captain Phillips"

The purpose of this article has been made through a Marxist analysis of the US film "Captain Phillips" (PaulGreengrass, 2013), based on a true story. I have found how the evolution of capitalism in the West continuesto consolidate the belief reified in a historical and geographical superiority of the political and socioeconomicwestern models regarding Africa and Asia lowers models. At the same time, through categories like dialecticalmaterialism, criticism of diffusionist theory and application of cognitive mapping to large geopoliticalspaces located in most poor areas of the world, I have realized a remark about currently being articulatingthe political unconscious of working class in rich countries and the poor in poor countries, establishing arelationship between the ideological representation that takes an individual from his historical reality (ona scale that moves from local to global), and how he has developed a mental ability to escape of the responsibilityto make a critical review of what's happening around him in all areas. Finally, through physicalspace captured in the film, I have realized a materialist critique of globalized business process that takesplace through the carriage of goods, outlining spatial and cognitively limits of the mentality of our time, bothamong "winners"as among the "losers", based on the spatial movement of capital.

La Ley de semillas en Argentina: la disputa por el control y el futuro de la agricultura

Desde la llegada de la revolución bioteconológica en la agricultura mundial, las corporaciones semilleras-agroquímicas han avanzado en el control del mercado internacional de alimentos, a partir de diversos mecanismos, entre ellos el de la legislación de derechos de propiedad intelectual. En América Latina, distintos gobiernos han procurado adecuar la legislación nacional a estas tendencias internacionales, con resultado dispar, ya que se ha generado una fuerte resistencia desde organizaciones populares. Argentina, un país de temprana inserción en el mercado internacional de alimentos y de rápida adopción de los derechos de obtentor, está atravesado hoy por una nueva fase de esta disputa, ante la posible sanción de una nueva Ley de Semillas, en la que empresa estadounidense Monsanto está involucrada. Este trabajo hace un repaso del panorama actual desde un punto de vista geográfico, prestando especial atención a las estrategias de las organizaciones que se oponen a la nueva legislación.

Imperative, subjunctive, and the desiderative-appellative space in Spanish

After defining the “enunciative scheme” (sentence type) as a communicative unit, the imperative is characterized as a morphologized modality of appellative kind used when the following conditions occur: appellative meaning, 2nd person, future tense and absence of negation. In Spanish, any variation of any of these requirements determines that the subjunctive is used. We reject the idea that the imperative is a variant of subjunctive specialized in appellative function and that both modes share a desiderative morpheme. Working in this way means attributing to a morphological category of the verb a property that actually corresponds to the enunciative schemes (sentence types). We propose to integrate the imperative and subjunctive in the framework of what we call the “desiderative-appellative space”. This “space” brings together various grammatical or grammaticalized means based on the imperative and the subjunctive. Semantically, it is organized around a component of desirability (action appears as desirable) that, by varying several factors, configures a route that goes from a center (the imperative) to a periphery (the expression of desire).

A Validation Study of Vascular Cognitive Impairment Genetics Meta-Analysis Findings in an Independent Collaborative Cohort

Vascular cognitive impairment (VCI), including its severe form, vascular dementia (VaD), is the second most common form of dementia. The genetic etiology of sporadic VCI remains largely unknown. We previously conducted a systematic review and meta-analysis of all published genetic association studies of sporadic VCI prior to 6 July 2012, which demonstrated that APOE (ɛ4, ɛ2) and MTHFR (rs1801133) variants were associated with susceptibility for VCI. De novo genotyping was conducted in a new independent relatively large collaborative European cohort of VaD (nmax = 549) and elderly non-demented samples (nmax = 552). Where available, genotype data derived from Illumina's 610-quad array for 1210 GERAD1 control samples were also included in analyses of genes examined. Associations were tested using the Cochran-Armitage trend test: MTHFR rs1801133 (OR = 1.36, 95% CI 1.16-1.58, p = <0.0001), APOE rs7412 (OR = 0.62, 95% CI 0.42-0.90, p = 0.01), and APOE rs429358 (OR = 1.59, 95% CI 1.17-2.16, p = 0.003). Association was also observed with APOE epsilon alleles; ɛ4 (OR = 1.85, 95% CI 1.35-2.52, p = <0.0001) and ɛ2 (OR = 0.67, 95% CI 0.46-0.98, p = 0.03). Logistic Regression and Bonferroni correction in a subgroup of the cohort adjusted for gender, age, and population maintained the association of APOE rs429358 and ɛ4 allele.

Gestengestützte Schema- und Datenexploration

Der Zugang zu Datenbanken über die universelle Abfragesprache SQL stellt für Nicht-Spezialisten eine große Herausforderung dar. Als eine benutzerfreundliche Alternative wurden daher seit den 1970er-Jahren unterschiedliche visuelle Abfragesprachen (Visual Query Languages, kurz VQLs) für klassische PCs erforscht. Ziel der vorliegenden Arbeit ist es, eine generische VQL zu entwickeln und zu erproben, die eine gestenbasierte Exploration von Datenbanken auf Schema- und Instanzdatenebene für mobile Endgeräte, insbesondere Tablets, ermöglicht. Dafür werden verschiedene Darstellungsformen, Abfragestrategien und visuelle Hints für Fremdschlüsselbeziehungen untersucht, die den Benutzer bei der Navigation durch die Daten unterstützen. Im Rahmen einer Anforderungsanalyse erwies sich die Visualisierung der Daten und Beziehungen mittels einer platzsparenden geschachtelten NF2-Darstellung als besonders vorteilhaft. Zur Steuerung der Datenbankexploration wird eine geeignete Gestensprache, bestehend aus Stroke-, Multitouch- und Mid-Air-Gesten, vorgestellt. Das Gesamtkonzept aus Darstellung und Gestensteuerung wurde anhand des im Rahmen dieser Arbeit entwickelten GBXT-Prototyps auf seine reale Umsetzbarkeit hin, als plattformunabhängige Single-Page-Application für verschiedene mobile Endgeräte mittels JavaScript und HTML5/CSS3 untersucht.

Ambulance Treatment Space Ergonomic Layout

This is the first time a multidisciplinary team has employed an iterative co-design method to determine the ergonomic layout of an emergency ambulance treatment space. This process allowed the research team to understand how treatment protocols were performed and developed analytical tools to reach an optimum configuration towards ambulance design standardisation. Fusari conducted participatory observations during 12-hour shifts with front-line ambulance clinicians, hospital staff and patients to understand the details of their working environments whilst on response to urgent and emergency calls. A simple yet accurate 1:1 mock-up of the existing ambulance was built for detailed analysis of these procedures through simulations. Paramedics were called in to participate in interviews and role-playing inside the model to recreate tasks, how they are performed, the equipment used and to understand the limitations of the current ambulance. The use of Link Analysis distilled 5 modes of use. In parallel, an exhaustive audit of all equipment and consumables used in ambulances was performed (logging and photography) to define space use. These developed 12 layout options for refinement and CAD modelling and presented back to paramedics. The preferred options and features were then developed into a full size test rig and appearance model. Two key studies informed the process. The 2005 National Patient Safety Agency funded study “Future Ambulances” outlined 9 design challenges for future standardisation of emergency vehicles and equipment. Secondly, the 2007 EPSRC funded “Smart Pods” project investigated a new system of mobile urgent and emergency medicine to treat patients in the community. A full-size mobile demonstrator unit featuring the evidence-based ergonomic layout was built for clinical tests through simulated emergency scenarios. Results from clinical trials clearly show that the new layout improves infection control, speeds up treatment, and makes it easier for ambulance crews to follow correct clinical protocols.

The pathology of command and control: a formal synthesis

One of the most important theories in the study of environmental governance and policy is the pathology of command and control, which describes the negative consequences of top-down, technocratic governance of social and ecological systems. However, to date, this theory has been expressed somewhat inconsistently and informally in the literature, even by the seminal works that have established its importance and popularized it. This presents a problem for the sustainability science community if it cannot be sure of the precise details of one of its most important theories. Without such precision, applications and tests of various elements of the theory cannot be conducted reliably to advance the knowledge of environmental governance. I address this problem by synthesizing several seminal works to formalize this theory. The formalization involves the identification of the individual elements of the theory and a diagrammatic description of their relationships with each other that unfold in a series of semi-independent causal paths. Ideally, with such a formalization, scholars can use this theory more reliably and more meaningfully in their future work. I conclude by discussing the implications this theory has for the governance of natural resources.

Development of Effortful Control as a Moderator of the Longitudinal Relations of Negative Reactivity and Symptoms in Preschool

Thesis (Ph.D.)--University of Washington, 2016-08

Analysis of physical pore space characteristics of two pyrolytic biochars and potential as microhabitat

Studies on hacking have typically focused on motivational aspects and general personality traits of the individuals who engage in hacking; little systematic research has been conducted on predispositions that may be associated not only with the choice to pursue a hacking career but also with performance in either naïve or expert populations. Here, we test the hypotheses that two traits that are typically enhanced in autism spectrum disorders—attention to detail and systemizing—may be positively related to both the choice of pursuing a career in information security and skilled performance in a prototypical hacking task (i.e., crypto-analysis or code-breaking). A group of naïve participants and of ethical hackers completed the Autism Spectrum Quotient, including an attention to detail scale, and the Systemizing Quotient (Baron-Cohen et al., 2001, 2003). They were also tested with behavioral tasks involving code-breaking and a control task involving security X-ray image interpretation. Hackers reported significantly higher systemizing and attention to detail than non-hackers. We found a positive relation between self-reported systemizing (but not attention to detail) and code-breaking skills in both hackers and non-hackers, whereas attention to detail (but not systemizing) was related with performance in the X-ray screening task in both groups, as previously reported with naïve participants (Rusconi et al., 2015). We discuss the theoretical and translational implications of our findings.

Numerical analysis of the modal coupling at low resonances in a Colombian Andean Bandola in C using the finite element method

The work presented in this thesis is concerned with the dynamical behavior of a CBandola's acoustical box at low resonances -- Two models consisting of two and three coupled oscillators are proposed in order to analyse the response at the first two and three resonances, respectively -- These models describe the first resonances in a bandola as a combination of the lowest modes of vibration of enclosed air, top and back plates -- Physically, the coupling between these elements is caused by the fluid-structure interaction that gives rise to coupled modes of vibration for the assembled resonance box -- In this sense, the coupling in the models is expressed in terms of the ratio of effective areas and masses of the elements which is an useful parameter to control the coupling -- Numerical models are developed for the analysis of modal coupling which is performed using the Finite Element Method -- First, it is analysed the modal behavior of separate elements: enclosed air, top plate and back plate -- This step is important to identify participating modes in the coupling -- Then, a numerical model of the resonance box is used to compute the coupled modes -- The computation of normal modes of vibration was executed in the frequency range of 0-800Hz -- Although the introduced models of coupled oscillators only predict maximum the first three resonances, they also allow to study qualitatively the coupling between the rest of the computed modes in the range -- Considering that dynamic response of a structure can be described in terms of the modal parameters, this work represents, in a good approach, the basic behavior of a CBandola, although experimental measurements are suggested as further work to verify the obtained results and get more information about some characteristics of the coupled modes, for instance, the phase of vibration of the air mode and the radiation e ciency