979 resultados para Conveying machinery


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A prototype presentation system base is described. It offers mechanisms, tools, and ready-made parts for building user interfaces. A general user interface model underlies the base, organized around the concept of a presentation: a visible text or graphic for conveying information. Te base and model emphasize domain independence and style independence, to apply to the widest possible range of interfaces. The primitive presentation system model treats the interface as a system of processes maintaining a semantic relation between an application data base and a presentation data base, the symbolic screen description containing presentations. A presenter continually updates the presentation data base from the application data base. The user manipulates presentations with a presentation editor. A recognizer translates the user's presentation manipulation into application data base commands. The primitive presentation system can be extended to model more complex systems by attaching additional presentation systems. In order to illustrate the model's generality and descriptive capabilities, extended model structures for several existing user interfaces are discussed. The base provides support for building the application and presentation data bases, linked together into a single, uniform network, including descriptions of classes of objects as we as the objects themselves. The base provides an initial presentation data base network graphics to continually display it, and editing functions. A variety of tools and mechanisms help create and control presenters and recognizers. To demonstrate the base's utility, three interfaces to an operating system were constructed, embodying different styles: icons, menu, and graphical annotation.

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The present work examines the beginnings of ancient hermeneutics. More specifically, it discusses the connection between the rise of the practice of allegoresis, on the one hand, and the emergence of the first theory of figurative language, on the other. Thus, this book investigates the specific historical and cultural circumstances that enabled the ancient Greeks not only to discover the possibility of allegorical interpretation, but also to treat figurative language as a philosophical problem. By posing difficulties in understanding the enigmatic sense of various esoteric doctrines, poems, oracles and riddles, figurative language created the context for theoretical reflection on the meaning of these “messages”. Hence, ancient interpreters began to ponder over the nature and functions of figurative (“enigmatic”) language as well as over the techniques of its proper use and interpretation. Although the practice of allegorical interpretation was closely linked to the development of the whole of ancient philosophy, the present work covers only the period from the 6th to the 4th century B.C. It concentrates, then, on the philosophical and cultural consequences of allegoresis in the classical age. The main thesis advocated here has it that the ancient Greeks were in-clined to regard allegory as a cognitive problem rather than merely as a stylistic or a literary one. When searching for the hidden meanings of various esoteric doc-trines, poems, oracles and riddles, ancient interpreters of these “messages” assumed allegory to be the only tool suitable for articulating certain matters. In other words, it was their belief that the use of figurative language resulted from the necessity of expressing things that were otherwise inexpressible. The present work has been organized in the following manner. The first part contains historical and philological discussions that provide the point of departure for more philosophical considerations. This part consists of two introductory chapters. Chapter one situates the practice of allegorical interpretation at the borderline of two different traditions: the rhetorical-grammatical and the hermeneutical. In order to clearly differentiate between the two, chapter one distinguishes between allegory and allegoresis, on the one hand, and allegoresis and exegesis, on the other. While pointing to the conventionality (and even arbitrariness) of such distinctions, the chapter argues, nevertheless, for their heuristic usefulness. The remaining part of chapter one focuses on a historical and philological reconstruction of the most important conceptual tools of ancient hermeneutics. Discussing the semantics of such terms as allēgoría, hypónoia, ainigma and symbolon proves important for at least two crucial reasons. Firstly, it reveals the mutual affinity between allegoresis and divination, i.e., practices that are inherently connected with the need to discover the latent meaning of the “message” in question (whether poem or oracle). Secondly, these philological analyses bring to light the specificity of the ancient understanding of such concepts as allegory or symbol. It goes without saying that antiquity employed these terms in a manner quite disparate from modernity. Chapter one concludes with a discussion of ancient views on the cognitive value of figurative (“enigmatic”) language. Chapter two focuses on the role that allegoresis played in the process of transforming mythos into logos. It is suggested here that it was the practice of allegorical interpretation that made it possible to preserve the traditional myths as an important point of reference for the whole of ancient philosophy. Thus, chapter two argues that the existence of a clear opposition between mythos into logos in Preplatonic philosophy is highly questionable in light of the indisputable fact that the Presocratics, Sophists and Cynics were profoundly convinced about the cognitive value of mythos (this conviction was also shared by Plato and Aristotle, but their attitude towards myth was more complex). Consequently, chapter two argues that in Preplatonic philosophy, myth played a function analogous to the concepts discussed in chapter one (i.e., hidden meanings, enigmas and symbols), for in all these cases, ancient interpreters found tools for conveying issues that were otherwise difficult to convey. Chapter two concludes with a classification of various types of allegoresis. Whilst chapters one and two serve as a historical and philological introduction, the second part of this book concentrates on the close relationship between the development of allegoresis, on the one hand, and the flowering of philosophy, on the other. Thus, chapter three discusses the crucial role that allegorical interpretation came to play in Preplatonic philosophy, chapter four deals with Plato’s highly complex and ambivalent attitude to allegoresis, and chapter five has been devoted to Aristotle’s original approach to the practice of allegorical interpretation. It is evident that allegoresis was of paramount importance for the ancient thinkers, irrespective of whether they would value it positively (Preplatonic philosophers and Aristotle) or negatively (Plato). Beginning with the 6th century B.C., the ancient practice of allegorical interpretation is motivated by two distinct interests. On the one hand, the practice of allegorical interpretation reflects the more or less “conservative” attachment to the authority of the poet (whether Homer, Hesiod or Orpheus). The purpose of this apologetic allegoresis is to exonerate poetry from the charges leveled at it by the first philosophers and, though to a lesser degree, historians. Generally, these allegorists seek to save the traditional paideia that builds on the works of the poets. On the other hand, the practice of allegorical interpretation reflects also the more or less “progressive” desire to make original use of the authority of the poet (whether Homer, Hesiod or Orpheus) so as to promote a given philosophical doctrine. The objective of this instrumental allegoresis is to exculpate philosophy from the accusations brought against it by the more conservative circles. Needless to say, these allegorists significantly contribute to the process of the gradual replacing of the mythical view of the world with its more philosophical explanation. The present book suggests that it is the philosophy of Aristotle that should be regarded as a sort of acme in the development of ancient hermeneutics. The reasons for this are twofold. On the one hand, the Stagirite positively values the practice of allegoresis, rehabilitating, thus, the tradition of Preplatonic philosophy against Plato. And, on the other hand, Aristotle initiates the theoretical reflection on figurative (“enigmatic”) language. Hence, in Aristotle we encounter not only the practice of allegoresis, but also the theory of allegory (although the philosopher does not use the term allēgoría). With the situation being as it is, the significance of Aristotle’s work cannot be overestimated. First of all, the Stagirite introduces the concept of metaphor into the then philosophical considerations. From that moment onwards, the phenomenon of figurative language becomes an important philosophical issue. After Aristo-tle, the preponderance of thinkers would feel obliged to specify the rules for the appropriate use of figurative language and the techniques of its correct interpretation. Furthermore, Aristotle ascribes to metaphor (and to various other “excellent” sayings) the function of increasing and enhancing our knowledge. Thus, according to the Stagirite, figurative language is not only an ornamental device, but it can also have a significant explanatory power. Finally, Aristotle observes that figurative expressions cause words to become ambiguous. In this context, the philosopher notices that ambiguity can enrich the language of a poet, but it can also hinder a dialectical discussion. Accordingly, Aristotle is inclined to value polysemy either positively or negatively. Importantly, however, the Stagirite is perfectly aware of the fact that in natural languages ambiguity is unavoidable. This is why Aristotle initiates a syste-matic reflection on the phenomenon of ambiguity and distinguishes its various kinds. In Aristotle, ambiguity is, then, both a problem that needs to be identified and a tool that can help in elucidating intricate philosophical issues. This unique approach to ambiguity and figurative (“enigmatic”) language enabled Aristotle to formulate invaluable intuitions that still await appropriate recognition.

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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

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Dissertação apresentada à Universidade Fernando Pessoa como parte dos requisitos para a obtenção do grau de Mestre em Docência e Gestão da Educação, especialização em Administração Escolar e Administração Educacional

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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

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NetSketch is a tool that enables the specification of network-flow applications and the certification of desirable safety properties imposed thereon. NetSketch is conceived to assist system integrators in two types of activities: modeling and design. As a modeling tool, it enables the abstraction of an existing system so as to retain sufficient enough details to enable future analysis of safety properties. As a design tool, NetSketch enables the exploration of alternative safe designs as well as the identification of minimal requirements for outsourced subsystems. NetSketch embodies a lightweight formal verification philosophy, whereby the power (but not the heavy machinery) of a rigorous formalism is made accessible to users via a friendly interface. NetSketch does so by exposing tradeoffs between exactness of analysis and scalability, and by combining traditional whole-system analysis with a more flexible compositional analysis approach based on a strongly-typed, Domain-Specific Language (DSL) to specify network configurations at various levels of sketchiness along with invariants that need to be enforced thereupon. In this paper, we overview NetSketch, highlight its salient features, and illustrate how it could be used in applications, including the management/shaping of traffic flows in a vehicular network (as a proxy for CPS applications) and in a streaming media network (as a proxy for Internet applications). In a companion paper, we define the formal system underlying the operation of NetSketch, in particular the DSL behind NetSketch's user-interface when used in "sketch mode", and prove its soundness relative to appropriately-defined notions of validity.

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NetSketch is a tool for the specification of constrained-flow applications and the certification of desirable safety properties imposed thereon. NetSketch is conceived to assist system integrators in two types of activities: modeling and design. As a modeling tool, it enables the abstraction of an existing system while retaining sufficient information about it to carry out future analysis of safety properties. As a design tool, NetSketch enables the exploration of alternative safe designs as well as the identification of minimal requirements for outsourced subsystems. NetSketch embodies a lightweight formal verification philosophy, whereby the power (but not the heavy machinery) of a rigorous formalism is made accessible to users via a friendly interface. NetSketch does so by exposing tradeoffs between exactness of analysis and scalability, and by combining traditional whole-system analysis with a more flexible compositional analysis. The compositional analysis is based on a strongly-typed Domain-Specific Language (DSL) for describing and reasoning about constrained-flow networks at various levels of sketchiness along with invariants that need to be enforced thereupon. In this paper, we define the formal system underlying the operation of NetSketch, in particular the DSL behind NetSketch's user-interface when used in "sketch mode", and prove its soundness relative to appropriately-defined notions of validity. In a companion paper [6], we overview NetSketch, highlight its salient features, and illustrate how it could be used in two applications: the management/shaping of traffic flows in a vehicular network (as a proxy for CPS applications) and in a streaming media network (as a proxy for Internet applications).

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In this PhD study, mathematical modelling and optimisation of granola production has been carried out. Granola is an aggregated food product used in breakfast cereals and cereal bars. It is a baked crispy food product typically incorporating oats, other cereals and nuts bound together with a binder, such as honey, water and oil, to form a structured unit aggregate. In this work, the design and operation of two parallel processes to produce aggregate granola products were incorporated: i) a high shear mixing granulation stage (in a designated granulator) followed by drying/toasting in an oven. ii) a continuous fluidised bed followed by drying/toasting in an oven. In addition, the particle breakage of granola during pneumatic conveying produced by both a high shear granulator (HSG) and fluidised bed granulator (FBG) process were examined. Products were pneumatically conveyed in a purpose built conveying rig designed to mimic product conveying and packaging. Three different conveying rig configurations were employed; a straight pipe, a rig consisting two 45° bends and one with 90° bend. It was observed that the least amount of breakage occurred in the straight pipe while the most breakage occurred at 90° bend pipe. Moreover, lower levels of breakage were observed in two 45° bend pipe than the 90° bend vi pipe configuration. In general, increasing the impact angle increases the degree of breakage. Additionally for the granules produced in the HSG, those produced at 300 rpm have the lowest breakage rates while the granules produced at 150 rpm have the highest breakage rates. This effect clearly the importance of shear history (during granule production) on breakage rates during subsequent processing. In terms of the FBG there was no single operating parameter that was deemed to have a significant effect on breakage during subsequent conveying. A population balance model was developed to analyse the particle breakage occurring during pneumatic conveying. The population balance equations that govern this breakage process are solved using discretization. The Markov chain method was used for the solution of PBEs for this process. This study found that increasing the air velocity (by increasing the air pressure to the rig), results in increased breakage among granola aggregates. Furthermore, the analysis carried out in this work provides that a greater degree of breakage of granola aggregates occur in line with an increase in bend angle.

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RNA editing is a biological phenomena that alters nascent RNA transcripts by insertion, deletion and/or substitution of one or a few nucleotides. It is ubiquitous in all kingdoms of life and in viruses. The predominant editing event in organisms with a developed central nervous system is Adenosine to Inosine deamination. Inosine is recognized as Guanosine by the translational machinery and reverse-transcriptase. In primates, RNA editing occurs frequently in transcripts from repetitive regions of the genome. In humans, more than 500,000 editing instances have been identified, by applying computational pipelines on available ESTs and high-throughput sequencing data, and by using chemical methods. However, the functions of only a small number of cases have been studied thoroughly. RNA editing instances have been found to have roles in peptide variants synthesis by non-synonymous codon substitutions, transcript variants by alterations in splicing sites and gene silencing by miRNAs sequence modifications. We established the Database of RNA EDiting (DARNED) to accommo-date the reference genomic coordinates of substitution editing in human, mouse and fly transcripts from published literatures, with additional information on edited genomic coordinates collected from various databases e.g. UCSC, NCBI. DARNED contains mostly Adenosine to Inosine editing and allows searches based on genomic region, gene ID, and user provided sequence. The Database is accessible at http://darned.ucc.ie RNA editing instances in coding region are likely to result in recoding in protein synthesis. This encouraged me to focus my research on the occurrences of RNA editing specific CDS and non-Alu exonic regions. By applying various filters on discrepancies between available ESTs and their corresponding reference genomic sequences, putative RNA editing candidates were identified. High-throughput sequencing was used to validate these candidates. All predicted coordinates appeared to be either SNPs or unedited.

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Vascular smooth muscle cells (VSMC) are one of the key players in the pathogenesis of cardiovascular diseases. The origin of neointimal VSMC has thus become a prime focus of research. VSMC originate from multiple progenitors cell types. In embryo the well-defined sources of VSMC include; neural crest cells, proepicardial cells and EPC. In adults, though progenitor cells from bone marrow (BM), circulation and tissues giving rise to SMC have been identified, no progress has been made in terms of isolating highly proliferative clonal population of adult stem cells with potential to differentiate into SMC. Smooth muscle like stem progenitor cells (SMSPC) were isolated from cardiopulmonary bypass filters of adult patients undergoing CABG. Rat SMSPC have previously been isolated by our group from the bone marrow of Fischer rats and also from the peripheral blood of monocrotaline induced pulmonary hypertension (MCT-PHTN) animal model. Characterization of novel SMSPC exhibited stem cell characteristics and machinery for differentiation into SMC. The expression of Isl-1 on SMSPC provided unique molecular identity to these circulating stem progenitor cells. The functional potential of SMSPC was determined by monitoring adoptive transfer of GFP+ SMSPC in rodent models of vascular injury; carotid injury and MCT-PHTN. The participation of SMSPC in vascular pathology was confirmed by quantifying the peripheral blood, and engrafted levels of SMSPC using RT-PCR. In terms of translating into clinical practice, SMSPC could be a good tool for detecting the atherosclerotic plaque burden. The current study demonstrates the existence of novel adult stem progenitor cells in circulation, with the potential role in vascular pathology.

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In this work we introduce a new mathematical tool for optimization of routes, topology design, and energy efficiency in wireless sensor networks. We introduce a vector field formulation that models communication in the network, and routing is performed in the direction of this vector field at every location of the network. The magnitude of the vector field at every location represents the density of amount of data that is being transited through that location. We define the total communication cost in the network as the integral of a quadratic form of the vector field over the network area. With the above formulation, we introduce a mathematical machinery based on partial differential equations very similar to the Maxwell's equations in electrostatic theory. We show that in order to minimize the cost, the routes should be found based on the solution of these partial differential equations. In our formulation, the sensors are sources of information, and they are similar to the positive charges in electrostatics, the destinations are sinks of information and they are similar to negative charges, and the network is similar to a non-homogeneous dielectric media with variable dielectric constant (or permittivity coefficient). In one of the applications of our mathematical model based on the vector fields, we offer a scheme for energy efficient routing. Our routing scheme is based on changing the permittivity coefficient to a higher value in the places of the network where nodes have high residual energy, and setting it to a low value in the places of the network where the nodes do not have much energy left. Our simulations show that our method gives a significant increase in the network life compared to the shortest path and weighted shortest path schemes. Our initial focus is on the case where there is only one destination in the network, and later we extend our approach to the case where there are multiple destinations in the network. In the case of having multiple destinations, we need to partition the network into several areas known as regions of attraction of the destinations. Each destination is responsible for collecting all messages being generated in its region of attraction. The complexity of the optimization problem in this case is how to define regions of attraction for the destinations and how much communication load to assign to each destination to optimize the performance of the network. We use our vector field model to solve the optimization problem for this case. We define a vector field, which is conservative, and hence it can be written as the gradient of a scalar field (also known as a potential field). Then we show that in the optimal assignment of the communication load of the network to the destinations, the value of that potential field should be equal at the locations of all the destinations. Another application of our vector field model is to find the optimal locations of the destinations in the network. We show that the vector field gives the gradient of the cost function with respect to the locations of the destinations. Based on this fact, we suggest an algorithm to be applied during the design phase of a network to relocate the destinations for reducing the communication cost function. The performance of our proposed schemes is confirmed by several examples and simulation experiments. In another part of this work we focus on the notions of responsiveness and conformance of TCP traffic in communication networks. We introduce the notion of responsiveness for TCP aggregates and define it as the degree to which a TCP aggregate reduces its sending rate to the network as a response to packet drops. We define metrics that describe the responsiveness of TCP aggregates, and suggest two methods for determining the values of these quantities. The first method is based on a test in which we drop a few packets from the aggregate intentionally and measure the resulting rate decrease of that aggregate. This kind of test is not robust to multiple simultaneous tests performed at different routers. We make the test robust to multiple simultaneous tests by using ideas from the CDMA approach to multiple access channels in communication theory. Based on this approach, we introduce tests of responsiveness for aggregates, and call it CDMA based Aggregate Perturbation Method (CAPM). We use CAPM to perform congestion control. A distinguishing feature of our congestion control scheme is that it maintains a degree of fairness among different aggregates. In the next step we modify CAPM to offer methods for estimating the proportion of an aggregate of TCP traffic that does not conform to protocol specifications, and hence may belong to a DDoS attack. Our methods work by intentionally perturbing the aggregate by dropping a very small number of packets from it and observing the response of the aggregate. We offer two methods for conformance testing. In the first method, we apply the perturbation tests to SYN packets being sent at the start of the TCP 3-way handshake, and we use the fact that the rate of ACK packets being exchanged in the handshake should follow the rate of perturbations. In the second method, we apply the perturbation tests to the TCP data packets and use the fact that the rate of retransmitted data packets should follow the rate of perturbations. In both methods, we use signature based perturbations, which means packet drops are performed with a rate given by a function of time. We use analogy of our problem with multiple access communication to find signatures. Specifically, we assign orthogonal CDMA based signatures to different routers in a distributed implementation of our methods. As a result of orthogonality, the performance does not degrade because of cross interference made by simultaneously testing routers. We have shown efficacy of our methods through mathematical analysis and extensive simulation experiments.

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Autophagy has been predominantly studied as a nonselective self-digestion process that recycles macromolecules and produces energy in response to starvation. However, autophagy independent of nutrient status has long been known to exist. Recent evidence suggests that this form of autophagy enforces intracellular quality control by selectively disposing of aberrant protein aggregates and damaged organelles--common denominators in various forms of neurodegenerative diseases. By definition, this form of autophagy, termed quality-control (QC) autophagy, must be different from nutrient-regulated autophagy in substrate selectivity, regulation and function. We have recently identified the ubiquitin-binding deacetylase, HDAC6, as a key component that establishes QC. HDAC6 is not required for autophagy activation per se; rather, it is recruited to ubiquitinated autophagic substrates where it stimulates autophagosome-lysosome fusion by promoting F-actin remodeling in a cortactin-dependent manner. Remarkably, HDAC6 and cortactin are dispensable for starvation-induced autophagy. These findings reveal that autophagosomes associated with QC are molecularly and biochemically distinct from those associated with starvation autophagy, thereby providing a new molecular framework to understand the emerging complexity of autophagy and therapeutic potential of this unique machinery.

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Rising antibiotic resistance among Escherichia coli, the leading cause of urinary tract infections (UTIs), has placed a new focus on molecular pathogenesis studies, aiming to identify new therapeutic targets. Anti-virulence agents are attractive as chemotherapeutics to attenuate an organism during disease but not necessarily during benign commensalism, thus decreasing the stress on beneficial microbial communities and lessening the emergence of resistance. We and others have demonstrated that the K antigen capsule of E. coli is a preeminent virulence determinant during UTI and more invasive diseases. Components of assembly and export are highly conserved among the major K antigen capsular types associated with UTI-causing E. coli and are distinct from the capsule biogenesis machinery of many commensal E. coli, making these attractive therapeutic targets. We conducted a screen for anti-capsular small molecules and identified an agent designated "C7" that blocks the production of K1 and K5 capsules, unrelated polysaccharide types among the Group 2-3 capsules. Herein lies proof-of-concept that this screen may be implemented with larger chemical libraries to identify second-generation small-molecule inhibitors of capsule biogenesis. These inhibitors will lead to a better understanding of capsule biogenesis and may represent a new class of therapeutics.

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G protein-coupled receptors (GPCRs) play an integral role in the signal transduction of an enormous array of biological phenomena, thereby serving to modulate at a molecular level almost all components of human biology. This role is nowhere more evident than in cardiovascular biology, where GPCRs regulate such core measures of cardiovascular function as heart rate, contractility, and vascular tone. GPCR/ligand interaction initiates signal transduction cascades, and requires the presence of the receptor at the plasma membrane. Plasma membrane localization is in turn a function of the delivery of a receptor to and removal from the cell surface, a concept defined most broadly as receptor trafficking. This review illuminates our current view of GPCR trafficking, particularly within the cardiovascular system, as well as highlights the recent and provocative finding that components of the GPCR trafficking machinery can facilitate GPCR signaling independent of G protein activation.

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The beta 2-adrenergic receptor (beta 2AR) can be constitutively activated by mutations in the third intracellular loop. Whereas the wild-type receptor exists predominantly in an inactive conformation (R) in the absence of agonist, the mutant receptor appears to spontaneously adopt an active conformation (R*). We now demonstrate that not only is the mutant beta 2AR constitutively active, it is also constitutively desensitized and down-regulated. To assess whether the mutant receptor can constitutively engage a known element of the cellular desensitization machinery, the receptor was purified and reconstituted into phospholipid vesicles. These preparations retained the essential properties of the constitutively active mutant receptor: agonist-independent activity [to stimulate guanine nucleotide-binding protein (Gs)-GTPase] and agonist-specific increase in binding affinity. Moreover, the purified mutant receptor, in the absence of agonist, was phosphorylated by recombinant beta AR-specific kinase (beta ARK) in a fashion comparable to the agonist-occupied wild-type receptor. Thus, the conformation of the mutated receptor is equivalent to the active conformation (R*), which stimulates Gs protein and is identical to the beta ARK substrate.