Habitual chocolate consumption and the risk of incident heart failure among healthy men and women

Acknowledgments The authors would like to thank the participants of the EPIC-Norfolk cohort. We thank the nutritionist team and data management team of the EPIC-Norfolk cohort. The EPIC-Norfolk study was supported by grants from the Medical Research Council and Cancer Research UK. Funders had no role in study design or interpretation of the findings.

Prior Antithrombotic Use is Associated with Favorable Mortality and Functional Outcomes in Acute Ischemic Stroke

Sources of Funding The GWTG-Stroke program is currently supported in part by a charitable contribution from Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership and the American Heart Association Pharmaceutical Roundtable. GWTG-Stroke has been funded in the past through support from Boehringer-Ingelheim and Merck. These funding agencies did not participate in design or analysis, manuscript preparation, or approval of this study.

Habitual chocolate consumption and the risk of incident heart failure among healthy men and women

Acknowledgments The authors would like to thank the participants of the EPIC-Norfolk cohort. We thank the nutritionist team and data management team of the EPIC-Norfolk cohort. The EPIC-Norfolk study was supported by grants from the Medical Research Council and Cancer Research UK. Funders had no role in study design or interpretation of the findings.

Contradições como força de mudança: o processo de formação continuada de professores do ensino médio enquanto potencializador da práxis transformadora à luz da teoria histórico-cultural

The intervention research proposed was based on the Cultural-Historical Theory based on the laws and logic of materialism historical-dialectical. Therefore, we tried to design a research process that involved all as responsible for the process. In the field of continuous teacher's training usually has been found dualistic relationship / paradoxical processes as a result of the adopted training models which are characterized by individualist human processes. The teacher training work sought to overcome this dualism, to promote the unveiling of the contradictions with regard to teaching models. As a hypothesis, we imagined that immersed in this process, teachers recognize such contradictions, and this recognition would make the contradictions become the driving force of change in teaching practice, realizing the teaching-learning-development triad as the basis of praxis. Aiming to develop a process of continuing education to bring results to the professional teachers development looking for answer the following research question: How and what the changes of teachers who participated in the Didactic-Formative Intervention process raised the quality of their teaching practices? In this context, the objective of the research was to develop a process of Didactic-Formative Intervention from the perspective of Cultural-Historical Theory with high school teachers in order to theorize about the changes in pedagogical practices of teachers and learn aspects that transform the essence teaching practice. The research involved two high school teachers of a public school in Uberlândia-MG. The training meetings took place at the school through a collective study group between the years 2013 and 2015. As procedures were used two interconnected aspects: classes observations, and a theoretical and methodological training, both for diagnosis and for the process evaluation, the second aspect has a formative dimension, and a didactic dimension (double meaning) to form didactically the teacher and to elaborate didactic procedures. The collected data were analyzed by observing the assumptions of the method, analysis by units and the processuality. As results teachers showed changes in their teaching practices regarding the organization of the pedagogical work and also centered their design educational actions based on learning and development of the students. The presence of continuous diagnosis during the classes, work with a systems of concepts and their conceptual links, problematization as a teaching method can be pointed as meaningful changes in their praxis. Regarding the training activities that emerged from the analysis of the compiled materials and analyzed throughout the process can be emphasized: forming a collective group of school teachers continuous training, diagnostics, development of practical activities, increase relationships among participants, the choice of scientific material used should have direct relation to the needs of the participants, promoting conditions that enable the emergence of contradictions between the pedagogical practice of teachers and teaching based on the perspective of the Cultural-Historical Theory. This research craved to develop and design a teachers' training processes that increase the quality of teachers life and ways of teaching in the Brazilian public school.

Structural and Biochemical Dissection of the Trehalose Biosynthetic Complex in Pathogenic Fungi

Trehalose is a non-reducing disaccharide essential for pathogenic fungal survival and virulence. The biosynthesis of trehalose requires the trehalose-6-phosphate synthase, Tps1, and trehalose-6-phosphate phosphatase, Tps2. More importantly, the trehalose biosynthetic pathway is absent in mammals, conferring this pathway as an ideal target for antifungal drug design. However, lack of germane biochemical and structural information hinders antifungal drug design against these targets.

In this dissertation, macromolecular X-ray crystallography and biochemical assays were employed to understand the structures and functions of proteins involved in the trehalose biosynthetic pathway. I report here the first eukaryotic Tps1 structures from Candida albicans (C. albicans) and Aspergillus fumigatus (A. fumigatus) with substrates or substrate analogs. These structures reveal the key residues involved in substrate binding and catalysis. Subsequent enzymatic assays and cellular assays highlight the significance of these key Tps1 residues in enzyme function and fungal stress response. The Tps1 structure captured in its transition-state with a non-hydrolysable inhibitor demonstrates that Tps1 adopts an “internal return like” mechanism for catalysis. Furthermore, disruption of the trehalose biosynthetic complex formation through abolishing Tps1 dimerization reveals that complex formation has regulatory function in addition to trehalose production, providing additional targets for antifungal drug intervention.

I also present here the structure of the Tps2 N-terminal domain (Tps2NTD) from C. albicans, which may be involved in the proper formation of the trehalose biosynthetic complex. Deletion of the Tps2NTD results in a temperature sensitive phenotype. Further, I describe in this dissertation the structures of the Tps2 phosphatase domain (Tps2PD) from C. albicans, A. fumigatus and Cryptococcus neoformans (C. neoformans) in multiple conformational states. The structures of the C. albicans Tps2PD -BeF3-trehalose complex and C. neoformans Tps2PD(D24N)-T6P complex reveal extensive interactions between both glucose moieties of the trehalose involving all eight hydroxyl groups and multiple residues of both the cap and core domains of Tps2PD. These structures also reveal that steric hindrance is a key underlying factor for the exquisite substrate specificity of Tps2PD. In addition, the structures of Tps2PD in the open conformation provide direct visualization of the conformational changes of this domain that are effected by substrate binding and product release.

Last, I present the structure of the C. albicans trehalose synthase regulatory protein (Tps3) pseudo-phosphatase domain (Tps3PPD) structure. Tps3PPD adopts a haloacid dehydrogenase superfamily (HADSF) phosphatase fold with a core Rossmann-fold domain and a α/β fold cap domain. Despite lack of phosphatase activity, the cleft between the Tps3PPD core domain and cap domain presents a binding pocket for a yet uncharacterized ligand. Identification of this ligand could reveal the cellular function of Tps3 and any interconnection of the trehalose biosynthetic pathway with other cellular metabolic pathways.

Combined, these structures together with significant biochemical analyses advance our understanding of the proteins responsible for trehalose biosynthesis. These structures are ready to be exploited to rationally design or optimize inhibitors of the trehalose biosynthetic pathway enzymes. Hence, the work described in this thesis has laid the groundwork for the design of Tps1 and Tps2 specific inhibitors, which ultimately could lead to novel therapeutics to treat fungal infections.

Spic'ing into Existence: Epitaph, Epithet, and the Ethnopoetic Imagination

Quién Es, Quién Somos? Spic’ing into Existence claims a four-fold close-reading: first, analysis of texts: from theoretical meditations to (prison) memoir and film. Second, a half dozen central figures appear, largely Latinx and black American. They cut across a score of registers, socio-economics, ideological reservations, but all are, as Carl Carlton sang, poetry in motion. Writers, poets, theologians, pathologists, artists, comedians, actors, students whose vocation is invocation, the inner surge of their calling. Third, the manuscript draws from a series of historical moments—from radical liberation of the late 60s, to contemporary student activism. Finally, this body of work is movement, in all its social, gestural, and kinesthetic viscera. From this last heading, we peel away layers of what I call the ethnopoet, the fascia undoing that reveals its bio-political anatomy, dressing its bare life with kinship speech. First, the social revolutions of the Civil Rights, Black Power, abolitionism, the Black Panthers and Young Lords, boycotts and jarring artistic performances. These events are superficial not in vain sense, but key epicenters of underground murmurings, the workings of a cunning assailant. She robs not lavish estates, but another day to breathe. Gesturally, as perhaps the interlocutor, lies this author, interspersing his own diatribes to conjure her presence. The final branch is admittedly the most intangible. Kinesthetically, we map the nimbleness, footwork lígera of what I call the ethnopoet. Ethnopoet is no mere aggregate of ethnicity and poetry, but like chemical reaction, the descriptor for its behavior under certain pressures, temperatures, and elements. Elusive and resisting confinement, and therefore definition, the ethnopoet is a shapeshifting figure of how racialized bodies [people of color] respond to hegemonic powers. She is, at bottom, however, a native translator, the plural-lensed subject whose loyalty is only to the imagination of a different world, one whose survival is not contingent upon her exploitation. The native translator’s constant re-calibrations of oppressive power apparatuses seem taxing at best, and near-impossible, at worst. To effectively navigate through these polarized loci, she must identify ideologies that in turn seek “affective liberatory sances” in relation to the dominant social order (43). In a kind of performative contradiction, she must marshall the knowledge necessary to “break with ideology” while speaking within it. Chicana Studies scholar, Chela Sandoval, describes this dual movement as “meta-ideologizing”: the appropriation of hegemonic ideological forms in order to transform them (82). Nuestros padres se subieron encima de La Bestia, y por eso somos pasageros a ese tren. Y ya, dentro su pansa, tenemos que ser vigilantes cuando plantamos las bombas. In Methodology of the Oppressed, Sandoval schematizes this oppositional consciousness around five principle categories: “equal rights,” “revolutionary,” “supremacist,” “separatist,” and “differential.” Taken by themselves, the first four modes appear mutually exclusive, incapable of occupying the same plane, until a fifth pillar emerges. Cinematographic in nature, differential consciousness, as Sandoval defines it, is “a kinetic motion that maneuvers, poetically transfigures, and orchestrates while demanding alienation, perversion, and reformation in both spectators and practitioners” (44). For Sandoval, then, differential consciousness is a methodology that privileges an incredible sense mobility, one reaching artistic sensibilities. Our fourth and final analytic of movement serves an apt example of this dual meaning. Lexically speaking, ‘movement’ may be regarded as a political mobilization of aggrieved populations (through sustained efforts), or the process of moving objects (people or otherwise) from one location to another. Praxis-wise, it is both action and ideal, content and form. Thus, an ethnic poetics must be regarded less as a series of stanzas, shortened lyric, or even arrangement of language, but as a lens through which peripheralized peoples kaleidecope ideological positions in an “original, eccentric, and queer sight” (43). Taking note of the advantages of postponing identifications, the thesis stands its ground on the term ethnopoet. Its abstraction is not dewey-eyed philosophy, but an anticipation of poetic justice, of what’s to come from callused hands. This thesis is divided into 7.5 chapters. The first maps out the ethnopoet’s cartographies of struggle. By revisiting that alleged Tío Tomas, Richard Rodriguez, we unearth the tensions that negatively, deny citizenship to one silo, but on the flipside, engender manifold ways of seeing, hearing, and moving . The second, through George Jackson’s prison memoirs, pans out from this ethnography of power, groping for an apparatus that feigns an impervious prestige: ‘the aesthetic regime of coercion.’ In half-way cut, the thesis sidesteps to spic into existence, formally announcing, through Aime Cesaire, myself, and Pedro Pietri, the poeticization of trauma. Such uplift denies New Age transcendence of self, but a rehearsal of our entrapment in these mortal envelopes. Thirdly, conscious of the bleeding ethnic body, we cut open the incipient corpse to observe her pathologist. Her native autopsies offer the ethnic body’s posthumous recognition, the ethnopoetics ability to speak for and through the dead. Chapter five examines prolific black artists—Beyonce and Kendrick Lamar—to elide the circumvention of their consumption via invoking radical black hi/her-stories, ones fragmenting the black body. Sixth, the paper compares the Black Power Salute of the 1968 Mexico City Olympics to Duke’s Mi Gente Boycott of their Latino Student Recruitment Weekend. Both wielded “silent gestures,” that shrewdly interfered with white noise of numbed negligence. Finally, ‘taking the mask off’ that are her functionalities, the CODA expounds on ethnopoet’s interiority, particularly after the rapid re-calibration of her politics. Through a rerun of El Chavo del Ocho, one of Mexican television’s most cherished shows, we tune into the heart-breaking indigence of barrio residents, only to marvel at the power of humor to, as Friday’s John Witherspoon put it, “fight another day.” This thesis is the tip of my tongue. Y por una vez, déjala que cante.

Numerical Investigation on the Heat Transfer Enhancement Using Micro/Nano Phase-Change Particulate Flow

The introduction of phase change material fluid and nanofluid in micro-channel heat sink design can significantly increase the cooling capacity of the heat sink because of the unique features of these two kinds of fluids. To better assist the design of a high performance micro-channel heat sink using phase change fluid and nanofluid, the heat transfer enhancement mechanism behind the flow with such fluids must be completely understood. A detailed parametric study is conducted to further investigate the heat transfer enhancement of the phase change material particle suspension flow, by using the two-phase non-thermal-equilibrium model developed by Hao and Tao (2004). The parametric study is conducted under normal conditions with Reynolds numbers of Re=600-900 and phase change material particle concentrations ¡Ü0.25 , as well as extreme conditions of very low Reynolds numbers (Re < 50) and high phase change material particle concentration (0.5-0.7) slurry flow. By using the two newly-defined parameters, named effectiveness factor and performance index, respectively, it is found that there exists an optimal relation between the channel design parameters, particle volume fraction, Reynolds number, and the wall heat flux. The influence of the particle volume fraction, particle size, and the particle viscosity, to the phase change material suspension flow, are investigated and discussed. The model was validated by available experimental data. The conclusions will assist designers in making their decisions that relate to the design or selection of a micro-pump suitable for micro or mini scale heat transfer devices. To understand the heat transfer enhancement mechanism of the nanofluid flow from the particle level, the lattice Boltzmann method is used because of its mesoscopic feature and its many numerical advantages. By using a two-component lattice Boltzmann model, the heat transfer enhancement of the nanofluid is analyzed, through incorporating the different forces acting on the nanoparticles to the two-component lattice Boltzmann model. It is found that the nanofluid has better heat transfer enhancement at low Reynolds numbers, and the Brownian motion effect of the nanoparticles will be weakened by the increase of flow speed.

Designing Short Term Wave Traces to Assess Wave Power Devices

In recent years modern numerical methods have been employed in the design of Wave Energy Converters (WECs), however the high computational costs associated with their use makes it prohibitive to undertake simulations involving statistically relevant numbers of wave cycles. Experimental tests in wave tanks could also be performed more efficiently and economically if short time traces, consisting of only a few wave cycles, could be used to evaluate the hydrodynamic characteristics of a particular device or design modification. Ideally, accurate estimations of device performance could be made utilizing results obtained from investigations with a relatively small number of wave cycles. However the difficulty here is that many WECs, such as the Oscillating Wave Surge Converter (OWSC), exhibit significant non-linearity in their response. Thus it is challenging to make accurate predictions of annual energy yield for a given spectral sea state using short duration realisations of that sea. This is because the non-linear device response to particular phase couplings of sinusoidal components within those time traces might influence the estimate of mean power capture obtained. As a result it is generally accepted that the most appropriate estimate of mean power capture for a sea state be obtained over many hundreds (or thousands) of wave cycles. This ensures that the potential influence of phase locking is negligible in comparison to the predictions made. In this paper, potential methods of providing reasonable estimates of relative variations in device performance using short duration sea states are introduced. The aim of the work is to establish the shortness of sea state required to provide statistically significant estimations of the mean power capture of a particular type of Wave Energy Converter. The results show that carefully selected wave traces can be used to reliably assess variations in power output due to changes in the hydrodynamic design or wave climate. 

Shakedown Analysis Considering Limited Kinematic Hardening Materials

In design or safety assessment of mechanical structures, the use of the Design by Analysis (DBA) route is a modern trend. However, for making possible to apply DBA to structures under variable loads, two basic failure modes considered by ASME or European Standards must be precluded. Those modes are the alternate plasticity and incremental collapse (with instantaneous plastic collapse as a particular case). Shakedown theory is a tool that permit us to assure that those kinds of failures will be avoided. However, in practical applications, very large nonlinear optimization problems are generated. Due to this facts, only in recent years have been possible to obtain algorithms sufficiently accurate, robust and efficient, for dealing with this class of problems. In this paper, one of these shakedown algorithms, developed for dealing with elastic ideally-plastic structures, is enhanced to include limited kinematic hardening, a more realistic material behavior. This is done in the continuous model by using internal thermodynamic variables. A corresponding discrete model is obtained using an axisymmetric mixed finite element with an internal variable. A thick wall sphere, under variable thermal and pressure loads, is used in an example to show the importance of considering the limited kinematic hardening in the shakedown calculations

Production planning, pricing and market coordination for news vendor problem with price dependent demand

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

Förbättring av tillgänglighet i tillgänglighetsanpassade naturreservat

More than half a million people in Sweden are affected by some sort of disability. During recreational activities in nature areas, these people might encounter difficulties such as inadequate accessibility. The Swedish society requires that all citizens should have the same possibilities. The purpose of this thesis is to improve the accessibility for people with disabilities. The aim is to examine occurring flaws in accessible nature reserves and suggest possible improvements.The questions that will be answered are as follows:• What flaws do accessible nature reserves have, and how do they affect the visitors?• What improvements can be made in nature reserves to increase accessibility?To answer the questions, a case study was done, where five different nature areas were visited. During the case study, various flaws in the accessibility were observed and analysed. Prior to the case study, requirements and scientific research regarding accessibility was studied. Using this, suggestions for improving the accessibility were made. . Most of the improvements that could be made in the studied nature reserves were presumed to be applicable in other nature reserves in Sweden.With the case study in mind, the accessibility was considered in need of various improvements. The accessibility was studied from three out of four of the Swedish disability association’s categories; physical, communicative, and informative accessibility. The flaws that were encountered in the studied areas were due to incorrect design, or insufficient maintenance. Most of the flaws could be corrected in simple ways, but the flaws that were due to incorrect design or planning would require more work. After the case study it was discovered that supposedly “accessible” trails, according to different websites, had varying levels of accessibility. An accessible recreational area will benefit all types of visitors, not only people with disabilities. It will be more convenient and enables visits with strollers. An area cannot be made accessible for all types of visitors, but can be made accessible for as many visitors as possible.

Avaliação da interação entre aflatoxina M1 e B1 com a fração proteica do leite

Dissertação composta por 02 artigos.

Evaluation and FMEA of Fabrication Techniques for Metallic Grating Couplers on Polymer Substrates with Low Glass Transition Temperatures

The main task is to analyze the state of the art of grating couplers production and low-cost polymer substrates. Then to provide a recommendation of a new or adapted process for the production of metallic gratings on polymer sheets, based on a Failure Mode and Effect Analysis (FMEA). In order to achieve that, this thesis is divided into four chapters. After the first introductory chapter, the second section provides details about the state-of-the-art in optical technology platforms with focus on polymers and their main features for the aimed application, such as flexibility, low cost and roll to roll compatibility. It defines then the diffraction gratings and their specifications and closes with the explanation of adhesion mechanisms of inorganic materials on polymer substrates. The third chapter discusses processing of grating couplers. It introduces the basic fabrication methods and details a selection of current fabrication schemes found in literature with an assessment of their potential use for the desired application. The last chapter is a FMEA analysis of the retained fabrication process, called Flip and Fuse, in order to check its capability to realize the grating structure.

NIR-spectroscopy for bioprocess monitoring & control

The Ingold port adaption of a free beam NIR spectrometer is tailored for optimal bioprocess monitoring and control. The device shows an excellent signal to noise ratio dedicated to a large free aperture and therefore a large sample volume. This can be seen particularly in the batch trajectories which show a high reproducibility. The robust and compact design withstands rough process environments as well as SIP/CIP cycles. Robust free beam NIR process analyzers are indispensable tools within the PAT/QbD framework for realtime process monitoring and control. They enable multiparametric, non-invasive measurements of analyte concentrations and process trajectories. Free beam NIR spectrometers are an ideal tool to define golden batches and process borders in the sense of QbD. Moreover, sophisticated data analysis both quantitative and MSPC yields directly to a far better process understanding. Information can be provided online in easy to interpret graphs which allow the operator to make fast and knowledge-based decisions. This finally leads to higher stability in process operation, better performance and less failed batches.