An allosteric role for receptor activity-modifying proteins in defining GPCR pharmacology

G protein-coupled receptors are allosteric proteins that control transmission of external signals to regulate cellular response. Although agonist binding promotes canonical G protein signalling transmitted through conformational changes, G protein-coupled receptors also interact with other proteins. These include other G protein-coupled receptors, other receptors and channels, regulatory proteins and receptor-modifying proteins, notably receptor activity-modifying proteins (RAMPs). RAMPs have at least 11 G protein-coupled receptor partners, including many class B G protein-coupled receptors. Prototypic is the calcitonin receptor, with altered ligand specificity when co-expressed with RAMPs. To gain molecular insight into the consequences of this protein–protein interaction, we combined molecular modelling with mutagenesis of the calcitonin receptor extracellular domain, assessed in ligand binding and functional assays. Although some calcitonin receptor residues are universally important for peptide interactions (calcitonin, amylin and calcitonin gene-related peptide) in calcitonin receptor alone or with receptor activity-modifying protein, others have RAMP-dependent effects, whereby mutations decreased amylin/calcitonin gene-related peptide potency substantially only when RAMP was present. Remarkably, the key residues were completely conserved between calcitonin receptor and AMY receptors, and between subtypes of AMY receptor that have different ligand preferences. Mutations at the interface between calcitonin receptor and RAMP affected ligand pharmacology in a RAMP-dependent manner, suggesting that RAMP may allosterically influence the calcitonin receptor conformation. Supporting this, molecular dynamics simulations suggested that the calcitonin receptor extracellular N-terminal domain is more flexible in the presence of receptor activity-modifying protein 1. Thus, RAMPs may act in an allosteric manner to generate a spectrum of unique calcitonin receptor conformational states, explaining the pharmacological preferences of calcitonin receptor-RAMP complexes. This provides novel insight into our understanding of G protein-coupled receptor-protein interaction that is likely broadly applicable for this receptor class.

O Ofício das Rezadeiras: um estudo antropológico sobre as práticas terapêuticas e a comunhão de crenças em Cruzeta/RN

The present Master´s dissertation aims to study the practices of the rezadeiras, Brazilian women healers, through an anthropological perspective. Special attention will be given to the understanding of these practices as a dynamic process in relation to those women who heal in Cruzeta (Seridó, Rio Grande do Norte), where is located our ethnographic research. For this research, twenty four rezadeiras were contacted and colaborated with our work plan. Among them, two were pentecostal rezadeiras and another one was member of the Jurema cult, an afro-brazilian religious cult. Similarities among these women healers were perceived in the research process, mostly in terms of their learning process and the use of certain objects and ritual techniques. However, apparent differences among them gave us the chance for understanding and reflecting on the actual heterogeneity of this world of specialists. Furthermore, i tried to capture the relations between the rezadeiras and the therapeutic practices from health professionals or the religious practices of religious leaders (Catholic, pentecostal, etc). It is possible to ascertain about the complementarity between therapeutic practices from different cultural logics. This complementarity is also perceived through the religious interchanges and transits among different healers, including those who have different religious beliefs. In this work, rituals are also described and they are a crucial factor to the understanding of this particular religious and therapeutic practice conducted by women. Following these ideas, our basic aim is to understand how the rezadeiras make interpretations about health and illness, specially those ones which are particular associated with their practices, the so called "doenças de rezadeiras"

Angler Perception and Population Dynamics of the Northern Snakehead (Channa argus) in the Potomac River & Tributaries

Our research sought to address the extent to which the northern snakehead (Channa argus), an invasive fish species, represents a threat to the Potomac River ecosystem. The first goal of our research was to survey the perceptions and opinions of recreational anglers on the effects of the snakehead population in the Potomac River ecosystem. To determine angler perceptions, we created and administered 113 surveys from June – September 2014 at recreational boat ramps along the Potomac River. Our surveys were designed to expand information collected during previous surveys conducted by the U.S. Fish and Wildlife Service. Our results indicated recreational anglers perceive that abundances and catch rates of target species, specifically largemouth bass, have declined since snakehead became established in the river. The second goal of our research was to determine the genetic diversity and potential of the snakehead population to expand in the Potomac River. We hypothesized that the effective genetic population size would be much less than the census size of the snakehead population in the Potomac River. We collected tissue samples (fin clippings) from 79 snakehead collected in a recreational tournament held between Fort Washington and Wilson’s Landing, MD on the Potomac River and from electrofishing sampling conducted by the Maryland Department of Natural Resources in Pomonkey Creek, a tributary of the Potomac River. DNA was extracted from the tissue samples and scored for 12 microsatellite markers, which had previously been identified for Potomac River snakehead. Microsatellite allele frequency data were recorded and analyzed in the software programs GenAlEx and NeEstimator to estimate heterozygosity and effective genetic population size. Resampling simulations indicated that the number of microsatellites and the number of fish analyzed provided sufficient precision. Simulations indicated that the effective population size estimate would expect to stabilize for samples > 70 individual snakehead. Based on a sample of 79 fish scored for 12 microsatellites, we calculated an Ne of 15.3 individuals. This is substantially smaller than both the sample size and estimated population size. We conclude that genetic diversity in the snakehead population in the Potomac River is low because the population has yet to recover from a genetic bottleneck associated with a founder effect due to their recent introduction into the system.

Large eddy simulation of shock boundary layer interaction control using micro-vortex generators

The performance of supersonic engine inlets and external aerodynamic surfaces can be critically affected by shock wave / boundary layer interactions (SBLIs), whose severe adverse pressure gradients can cause boundary layer separation. Currently such problems are avoided primarily through the use of boundary layer bleed/suction which can be a source of significant performance degradation. This study investigates a novel type of flow control device called micro-vortex generators (µVGs) which may offer similar control benefits without the bleed penalties. µVGs have the ability to alter the near-wall structure of compressible turbulent boundary layers to provide increased mixing of high speed fluid which improves the boundary layer health when subjected to flow disturbance. Due to their small size,µVGs are embedded in the boundary layer which provide reduced drag compared to the traditional vortex generators while they are cost-effective, physically robust and do not require a power source. To examine the potential of µVGs, a detailed experimental and computational study of micro-ramps in a supersonic boundary layer at Mach 3 subjected to an oblique shock was undertaken. The experiments employed a flat plate boundary layer with an impinging oblique shock with downstream total pressure measurements. The moderate Reynolds number of 3,800 based on displacement thickness allowed the computations to use Large Eddy Simulations without the subgrid stress model (LES-nSGS). The LES predictions indicated that the shock changes the structure of the turbulent eddies and the primary vortices generated from the micro-ramp. Furthermore, they generally reproduced the experimentally obtained mean velocity profiles, unlike similarly-resolved RANS computations. The experiments and the LES results indicate that the micro-ramps, whose height is h≈0.5δ, can significantly reduce boundary layer thickness and improve downstream boundary layer health as measured by the incompressible shape factor, H. Regions directly behind the ramp centerline tended to have increased boundary layer thickness indicating the significant three-dimensionality of the flow field. Compared to baseline sizes, smaller micro-ramps yielded improved total pressure recovery. Moving the smaller ramps closer to the shock interaction also reduced the displacement thickness and the separated area. This effect is attributed to decreased wave drag and the closer proximity of the vortex pairs to the wall. In the second part of the study, various types of µVGs are investigated including micro-ramps and micro-vanes. The results showed that vortices generated from µVGs can partially eliminate shock induced flow separation and can continue to entrain high momentum flux for boundary layer recovery downstream. The micro-ramps resulted in thinner downstream displacement thickness in comparison to the micro-vanes. However, the strength of the streamwise vorticity for the micro-ramps decayed faster due to dissipation especially after the shock interaction. In addition, the close spanwise distance between each vortex for the ramp geometry causes the vortex cores to move upwards from the wall due to induced upwash effects. Micro-vanes, on the other hand, yielded an increased spanwise spacing of the streamwise vortices at the point of formation. This resulted in streamwise vortices staying closer to the wall with less circulation decay, and the reduction in overall flow separation is attributed to these effects. Two hybrid concepts, named “thick-vane” and “split-ramp”, were also studied where the former is a vane with side supports and the latter has a uniform spacing along the centerline of the baseline ramp. These geometries behaved similar to the micro-vanes in terms of the streamwise vorticity and the ability to reduce flow separation, but are more physically robust than the thin vanes. Next, Mach number effect on flow past the micro-ramps (h~0.5δ) are examined in a supersonic boundary layer at M=1.4, 2.2 and 3.0, but with no shock waves present. The LES results indicate that micro-ramps have a greater impact at lower Mach number near the device but its influence decays faster than that for the higher Mach number cases. This may be due to the additional dissipation caused by the primary vortices with smaller effective diameter at the lower Mach number such that their coherency is easily lost causing the streamwise vorticity and the turbulent kinetic energy to decay quickly. The normal distance between the vortex core and the wall had similar growth indicating weak correlation with the Mach number; however, the spanwise distance between the two counter-rotating cores further increases with lower Mach number. Finally, various µVGs which include micro-ramp, split-ramp and a new hybrid concept “ramped-vane” are investigated under normal shock conditions at Mach number of 1.3. In particular, the ramped-vane was studied extensively by varying its size, interior spacing of the device and streamwise position respect to the shock. The ramped-vane provided increased vorticity compared to the micro-ramp and the split-ramp. This significantly reduced the separation length downstream of the device centerline where a larger ramped-vane with increased trailing edge gap yielded a fully attached flow at the centerline of separation region. The results from coarse-resolution LES studies show that the larger ramped-vane provided the most reductions in the turbulent kinetic energy and pressure fluctuation compared to other devices downstream of the shock. Additional benefits include negligible drag while the reductions in displacement thickness and shape factor were seen compared to other devices. Increased wall shear stress and pressure recovery were found with the larger ramped-vane in the baseline resolution LES studies which also gave decreased amplitudes of the pressure fluctuations downstream of the shock.

Trajetos cênicos do grupo parafolclórico da UFRN:que dança é essa?

This paper aims at studying UFRN Parafolclórico Group, whose aesthetic formation is subjected to our analysis, specially at its two last performances, that is, Flor do Lírio (Lily Flower), 2004, and Debaixo do Barro do Chão (Under the Mud of the Ground), 2008. Three targets are envisaged here: to analyze the aesthetic ideas backing Parafolclórico Group exhibitions; to evaluate how their many folk elements interact with different artist languages in order to compose a certain choreography; and finally, to identify the aesthetic conformation placed behind the two different choreographs of the last performances, their trends and innermost features that differentiate them. In accordance with the Analysis of Contents (BARDIN, 2006), interviews have been made with the choreographers and the staff of the spectacles, resulting in elucidating answers to the understanding of their thematic axis. On the first chapter we called attention to motivating subjects as recollection, personal experiences, bibliography research, research in loco regarded as propelling forces of the creative works. Herein, folk culture is depicted as a dynamic process opening a frank dialogue with contemporary events and reinforcing their continuity. On the second chapter, we approached the aesthetic conformation and the scenic elements (costumes, light, scenario, make-up), integrating the studied spectacles and disseminating folk songs in various ways. As what concerns the subjects discourse, we have obtained support in authors like Robatto (1994); Lobo; Navas (2008); Burke (1989); Canclini (2006); Dufrenne (2005); Medeiros (2005); Pavis (2005); Silva (2005), among others. Those authors have provided us with an indispensable theoretic support which, added to the interviews, convinced us that the Parafolclórico Group s aesthetic conception tends to identify itself with the artist languages and other techniques of that Group. It also made sure that the Group s course aims at an aesthetic conception which is not limited to popular culture manifestations, like dance, but admits to play with other media in order to communicate its art. In view of this situation, we arrived to two conclusions: first: the group s interchanges emphasize the dynamic character of popular culture which, by establishing contacts with different realities, receives influences capable of extending its own continuity; second: the contemporary state of arts also improves multiple interchanges opening way, so, for many accomplishments in their field. Therefore, UFRN Parafolclórico Group inserts itself in the contemporary scenery by performing new evaluations of the popular dances as long as it puts them in contact with different technical, aesthetic, artist and culture combinations

O Ofício das Rezadeiras: um estudo antropológico sobre as práticas terapêuticas e a comunhão de crenças em Cruzeta/RN

The present Master´s dissertation aims to study the practices of the rezadeiras, Brazilian women healers, through an anthropological perspective. Special attention will be given to the understanding of these practices as a dynamic process in relation to those women who heal in Cruzeta (Seridó, Rio Grande do Norte), where is located our ethnographic research. For this research, twenty four rezadeiras were contacted and colaborated with our work plan. Among them, two were pentecostal rezadeiras and another one was member of the Jurema cult, an afro-brazilian religious cult. Similarities among these women healers were perceived in the research process, mostly in terms of their learning process and the use of certain objects and ritual techniques. However, apparent differences among them gave us the chance for understanding and reflecting on the actual heterogeneity of this world of specialists. Furthermore, i tried to capture the relations between the rezadeiras and the therapeutic practices from health professionals or the religious practices of religious leaders (Catholic, pentecostal, etc). It is possible to ascertain about the complementarity between therapeutic practices from different cultural logics. This complementarity is also perceived through the religious interchanges and transits among different healers, including those who have different religious beliefs. In this work, rituals are also described and they are a crucial factor to the understanding of this particular religious and therapeutic practice conducted by women. Following these ideas, our basic aim is to understand how the rezadeiras make interpretations about health and illness, specially those ones which are particular associated with their practices, the so called "doenças de rezadeiras"

Suupa uchinaanchu : a construção da rede transnacional okinawana

Tese (doutorado)—Universidade de Brasília, Instituto de Ciências Sociais, Departamento de Antropologia, Programa de Pós-graduação em Antropologia Social, 2016.

A review on the recent history of wind power ramp forecasting.

Forecasting large and fast variations of wind power (the so called ramps) helps achieve the integration of large amounts of wind energy. This paper presents a survey on wind power ramp forecasting, reflecting the increasing interest on this topic observed since 2007. Three main aspects were identified from the literature: wind power ramp definition, ramp underlying meteorological causes and experi-ences in predicting ramps. In this framework, we additionally outline a number of recommendations and potential lines of research.

Identifying wind power ramp causes from multivariate datasets: a methodological proposal and its application to reanalysis data.

Forecasting abrupt variations in wind power generation (the so-called ramps) helps achieve large scale wind power integration. One of the main issues to be confronted when addressing wind power ramp forecasting is the way in which relevant information is identified from large datasets to optimally feed forecasting models. To this end, an innovative methodology oriented to systematically relate multivariate datasets to ramp events is presented. The methodology comprises two stages: the identification of relevant features in the data and the assessment of the dependence between these features and ramp occurrence. As a test case, the proposed methodology was employed to explore the relationships between atmospheric dynamics at the global/synoptic scales and ramp events experienced in two wind farms located in Spain. The achieved results suggested different connection degrees between these atmospheric scales and ramp occurrence. For one of the wind farms, it was found that ramp events could be partly explained from regional circulations and zonal pressure gradients. To perform a comprehensive analysis of ramp underlying causes, the proposed methodology could be applied to datasets related to other stages of the wind-topower conversion chain.

Copto-Arabic Universal Chronography. Between Antiquity, Judaism, Christianity and Islam The K. al-Tawārīkh of N. al-Khilāfa Abū Shākir Ibn al-Rāhib (655 Heg. / 973 Mart. / 1257 Chr. / 1569 Alex. / 6750 AM)

La obra histórica del erudito y enciclopedista de la edad de oro de la literatura árabe copta, de la cual el Dr. Samuel Moawad (Munster) está preparando una edición, representa en realidad una colección de tres tratados divididos artificialmente en 51 capítulos secuenciales. El núcleo cronológico es precedido por un largo tratado con 47 capítulos sobre cálculos astronómicos y eclesiásticos así como épocas históricas y calendarios de diferentes naciones. La parte histórica propia (ch. 48-50), de los cuales el llamado Chronicon orientale representa una deficiente revisión anónima, trata sucesivamente de historia universal, dinastías islámicas y patriarcas coptos. Un sumario histórico, así como dogmático, de los primeros siete/ocho concilios de la Iglesia cristiana (cap. 51) termina la compilación entera. El conocido historiador al-Makin Ibn al-.Amid hace un gran uso de la labor de su contemporáneo y, al parecer a través de él, los grandes historiadores musulmanes: Ibn Khaldun, Maqrizi o Qalqashandi hacen mención continua de Ibn al-Rahib. Más tarde en el siglo XVI, el K. al-Tawarikh fue traducido en etiópico y tuvo un gran impacto en la literatura histórica y computacional de los etíopes.

Trajetos cênicos do grupo parafolclórico da UFRN:que dança é essa?

This paper aims at studying UFRN Parafolclórico Group, whose aesthetic formation is subjected to our analysis, specially at its two last performances, that is, Flor do Lírio (Lily Flower), 2004, and Debaixo do Barro do Chão (Under the Mud of the Ground), 2008. Three targets are envisaged here: to analyze the aesthetic ideas backing Parafolclórico Group exhibitions; to evaluate how their many folk elements interact with different artist languages in order to compose a certain choreography; and finally, to identify the aesthetic conformation placed behind the two different choreographs of the last performances, their trends and innermost features that differentiate them. In accordance with the Analysis of Contents (BARDIN, 2006), interviews have been made with the choreographers and the staff of the spectacles, resulting in elucidating answers to the understanding of their thematic axis. On the first chapter we called attention to motivating subjects as recollection, personal experiences, bibliography research, research in loco regarded as propelling forces of the creative works. Herein, folk culture is depicted as a dynamic process opening a frank dialogue with contemporary events and reinforcing their continuity. On the second chapter, we approached the aesthetic conformation and the scenic elements (costumes, light, scenario, make-up), integrating the studied spectacles and disseminating folk songs in various ways. As what concerns the subjects discourse, we have obtained support in authors like Robatto (1994); Lobo; Navas (2008); Burke (1989); Canclini (2006); Dufrenne (2005); Medeiros (2005); Pavis (2005); Silva (2005), among others. Those authors have provided us with an indispensable theoretic support which, added to the interviews, convinced us that the Parafolclórico Group s aesthetic conception tends to identify itself with the artist languages and other techniques of that Group. It also made sure that the Group s course aims at an aesthetic conception which is not limited to popular culture manifestations, like dance, but admits to play with other media in order to communicate its art. In view of this situation, we arrived to two conclusions: first: the group s interchanges emphasize the dynamic character of popular culture which, by establishing contacts with different realities, receives influences capable of extending its own continuity; second: the contemporary state of arts also improves multiple interchanges opening way, so, for many accomplishments in their field. Therefore, UFRN Parafolclórico Group inserts itself in the contemporary scenery by performing new evaluations of the popular dances as long as it puts them in contact with different technical, aesthetic, artist and culture combinations

Relações entre o relevo e a organização espacial do uso e cobertura do solo no sudoeste do estado de Goiás

Dissertação (mestrado)—Universidade de Brasília, Instituto de Geociências, Pós-Graduação em Geologia, 2016.

Gestures of judgement and welcome in public spaces: hypervisible migrant newcomers in Darwin, Australia

This paper draws on ethnographic research to show how pigmentation intensities of skin and facial characteristics make bodies of colour recognisable in public spaces of Darwin, a small multiethnic and multiracial north Australian city. This paper shows that the visibility of newcomers, in particular, humanitarian migrants from countries in Africa, the Middle East and Asia, circulates negative sentiments of fear, anxiety and discomfort in public spaces when instantaneous judgements are made. These judgements of misrecognition made by residents of diverse ethnic and racial backgrounds lead to simmering tensions that unfold as visceral events of vulnerability in public spaces such as bus interchanges, neighbourhood streets, shopping centres and car parks. These events that have the potential to wound and numb bodies contribute to the “urban unconscious” of Darwin as a city where public spaces are safe with heightened surveillance. This paper argues, however, that events of hypervisibility, judgement and interracial tensions can unfold quite differently in public spaces if humanitarian migrants sense gestures of welcome, particularly from Aboriginals. Such fleeting moments of welcome in Darwin have the potential to bring together bodies with different histories and geographies of racialisation, so that multiple publics emerge through everyday habits of living with difference.

The training load of aerial skiing

This study quantified the training load experienced by elite aerial skiers. Nine elite female aerial skiers were monitored during 16 training sessions over a 13 day period. Time-motion, landing impact and heart rate (HR) data were measured from 688 jumps using integrated GPS, accelerometer and HR transmitters while rating of perceived exertion (RPE) was taken using Borg's scale. Each jump was delineated into five components from the GPS time-motion data to determine the work to rest ratios. Participants completed 16 ± 3 jumps per session with a work to rest ratio of 1.9:1 Heart rates averaged 65 ± 3.1% HRmax and peaked at 85 ± 4.4% HRmax while and an RPE score of 12 ± 1 was evoked. Landing impacts were significantly higher (p ≤ 0.001) when participants jumped off ramps with a larger take-off angle or when they completed jumps with a mid-air rotation. The training load experienced by elite aerial skiers may be causative of the high incidence of injuries reported. Significantly differing levels of impact load during the study suggest training load for these athletes can be easily modified and periodised allowing optimised performance and minimised injury.

Development of Safety Performance Functions for SafetyAnalyst Applications in Florida

In 2010, the American Association of State Highway and Transportation Officials (AASHTO) released a safety analysis software system known as SafetyAnalyst. SafetyAnalyst implements the empirical Bayes (EB) method, which requires the use of Safety Performance Functions (SPFs). The system is equipped with a set of national default SPFs, and the software calibrates the default SPFs to represent the agency’s safety performance. However, it is recommended that agencies generate agency-specific SPFs whenever possible. Many investigators support the view that the agency-specific SPFs represent the agency data better than the national default SPFs calibrated to agency data. Furthermore, it is believed that the crash trends in Florida are different from the states whose data were used to develop the national default SPFs. In this dissertation, Florida-specific SPFs were developed using the 2008 Roadway Characteristics Inventory (RCI) data and crash and traffic data from 2007-2010 for both total and fatal and injury (FI) crashes. The data were randomly divided into two sets, one for calibration (70% of the data) and another for validation (30% of the data). The negative binomial (NB) model was used to develop the Florida-specific SPFs for each of the subtypes of roadway segments, intersections and ramps, using the calibration data. Statistical goodness-of-fit tests were performed on the calibrated models, which were then validated using the validation data set. The results were compared in order to assess the transferability of the Florida-specific SPF models. The default SafetyAnalyst SPFs were calibrated to Florida data by adjusting the national default SPFs with local calibration factors. The performance of the Florida-specific SPFs and SafetyAnalyst default SPFs calibrated to Florida data were then compared using a number of methods, including visual plots and statistical goodness-of-fit tests. The plots of SPFs against the observed crash data were used to compare the prediction performance of the two models. Three goodness-of-fit tests, represented by the mean absolute deviance (MAD), the mean square prediction error (MSPE), and Freeman-Tukey R2 (R2FT), were also used for comparison in order to identify the better-fitting model. The results showed that Florida-specific SPFs yielded better prediction performance than the national default SPFs calibrated to Florida data. The performance of Florida-specific SPFs was further compared with that of the full SPFs, which include both traffic and geometric variables, in two major applications of SPFs, i.e., crash prediction and identification of high crash locations. The results showed that both SPF models yielded very similar performance in both applications. These empirical results support the use of the flow-only SPF models adopted in SafetyAnalyst, which require much less effort to develop compared to full SPFs.