Pharmacological evaluation of NF279 as a P2 receptor antagonist : structure-activity relationship studies of analogues of the P2 receptor antagonists Suramin and NF023 at native P2 receptor subtypes and ecto-nucleotidases

Zu Beginn der 70er Jahre wurde für Adenosin-5'-triphosphat (ATP), das bereits lange als innerhalb der Zelle vorkommender Energieträger bekannt war, eine extrazelluläre Wirkung als Neurotransmitter postuliert. Es dauerte allerdings noch eine Reihe von Jahren, bis die von der Arbeitsgruppe um G. Burnstock aufgestellte Hypothese der "purinergen Nerven" und die damit verbundene Existenz von sogenannten P2-Rezeptoren (früher purinerge Rezeptoren) allgemein anerkannt wurde. Heute besteht kein Zweifel mehr, dass ATP alle der unten genannten Anforderungen an eine als endogener Überträgerstoff innerhalb des vegetativen und zentralen Nervensystems fungierende Substanz erfüllt: • Synthese und Speicherung des entsprechenden Überträgerstoffes, • Freisetzung einer definierten Menge an Transmitter bei einem einlaufenden Aktionspotential, • Rezeptoren für die Reaktion mit dem Transmitter sowie • die rasche Inaktivierung des freigesetzten Neurotransmitters. ...More than 70 years ago, the effects of extracellular adenosine 5'-triphosphate (ATP), a newly identified and purified biomolecule at that time (Fiske and Subbarow, 1925; Lohmann, 1929) were observed by Drury and Szent-Györgyi (1929). Since then, many pharmacological studies were carried out with extracellular adenine nucleotides in various intact organ systems, isolated tissues, and purified cell preparations. Yet it was not until 1972 that Burnstock introduced the concept of "purinergic nerves" and suggested that ATP might fulfil the criteria generally regarded as necessary for establishing a substance as a neurotransmitter, summarised by Eccles (1964): • synthesis and storage of transmitter in nerve terminals Strips of guinea-pig taenia coli (GPTC) were shown to take up large amounts of tritium-labelled adenosine when incubated with tritium-labelled adenosine, adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate (ADP) and ATP. The nucleoside was rapidly converted into and retained largely as [ 3 H]-ATP (Su et al., 1971). • release of transmitter during nerve stimulation Spontaneous relaxation of GPTC as well as relaxations induced by nerve stimulation or nicotine, respectively, in the presence of compounds which block adrenergic and cholinergic responses were accompanied by a remarkable increase in release of tritium-labelled material from taenia coli incubated in [ 3 H]-adenosine (Su et al., 1971). • postjunctional responses to exogenous transmitters that mimic responses to nerve stimulation Burnstock et al. (1966) characterised ATP and ADP as the most potent inhibitory purine compounds in the gut and observed that the effects of ATP mimic more closely the inhibitory response of the taenia to non-adrenergic nerve-stimulation than to adrenergic nerve stimulation (Burnstock et al., 1970). enzymes that inactivate the transmitter and/or uptake systems for the transmitter or its breakdown products When ATP was added to a perfusion fluid recycled through the vasculature of the stomach, very little ATP remained, but the perfusate contained substantially increased amounts of adenosine and inosine, as well as some ADP and AMP (Burnstock et al., 1970). • drugs that can produce parallel blocking of potentiating effects on the responses of both exogenous transmitter and nerve stimulation Tachyphylaxis to ATP produced in the rabbit ileum resulted in a consistent depression of responses to non-adrenergic inhibitory nerve stimulation, whereas responses to adrenergic nerve stimulation remained unaffected (Burnstock et al., 1970). Lower concentrations of quinidine reduced and finally abolished relaxation of GPTC induced by noradrenaline (NA) and by adrenergic nerve stimulation. Using higher concentrations of the compound, relaxant responses of GPTC to ATP as well as to non-adrenergic inhibitory nerve stimulation were abolished (Burnstock et al., 1970). ..

Building a Department of Adult Education at the University of British Columbia, 1957-1977

The diversification of universities into different departments and programs of study have various explanations. The degree program in adult education at the University of British Columbia "the first of its kind in Canada " for example, began with influential administrators who proposed and authorized it in anticipation of student demand. They then hired a professor of adult education, Coolie Verner, who used his considerable institutional status to create a curriculum, attract students, conduct research, and hire additional staff through the 1960s. Although changing circumstances in the following decade lessened Verner's influence, he had created an enduring institutional structure. Verner's activities illustrate the role of individuals and internal politics in determining administrative units at a university and, as a consequence, in legitimizing the research and teaching that occurs within those structures

Cognitive modeling of social behaviors

To understand both individual cognition and collective activity, perhaps the greatest opportunity today is to integrate the cognitive modeling approach (which stresses how beliefs are formed and drive behavior) with social studies (which stress how relationships and informal practices drive behavior). The crucial insight is that norms are conceptualized in the individual mind as ways of carrying out activities. This requires for the psychologist a shift from only modeling goals and tasks —why people do what they do—to modeling behavioral patterns—what people do—as they are engaged in purposeful activities. Instead of a model that exclusively deduces actions from goals, behaviors are also, if not primarily, driven by broader patterns of chronological and located activities (akin to scripts). To illustrate these ideas, this article presents an extract from a Brahms simulation of the Flashline Mars Arctic Research Station (FMARS), in which a crew of six people are living and working for a week, physically simulating a Mars surface mission. The example focuses on the simulation of a planning meeting, showing how physiological constraints (e.g., hunger, fatigue), facilities (e.g., the habitat’s layout) and group decision making interact. Methods are described for constructing such a model of practice, from video and first-hand observation, and how this modeling approach changes how one relates goals, knowledge, and cognitive architecture. The resulting simulation model is a powerful complement to task analysis and knowledge-based simulations of reasoning, with many practical applications for work system design, operations management, and training

Iambic Metapoetics in Horace, Epodes 8 and 12

When in Book 1 of his Epistles Horace reflects back upon the beginning of his career in lyric poetry, he celebrates his adaptation of Archilochean iambos to the Latin language. He further states that while he followed the meter and spirit of Archilochus, his own iambi did not follow the matter and attacking words that drove the daughters of Lycambes to commit suicide (Epist. 1.19.23–5, 31).1 The paired erotic invectives, Epodes 8 and 12, however, thematize the poet’s sexual impotence and his disgust during encounters with a repulsive sexual partner. The tone of these Epodes is unmistakably that of harsh invective, and the virulent targeting of the mulieres’ revolting bodies is precisely in line with an Archilochean poetics that uses sexually-explicit, graphic obscenities as well as animal comparisons for the sake of a poetic attack. Epodes 8 and 12 may, in fact, offer Roman culture’s most overtly misogynistic tone.

Gender Reversals and Intertextuality in Tibullus

This paper argues that Tibullus’ practice of altering the gender of his intertextual references destabilizes gender as a biological, social, and even grammatical category in his elegies. In 1.8, Tibullus draws on images of women’s adornment from Callimachus, Philitas, and Propertius to create the opening image of the puer Marathus. In 2.6, Tibullus draws from Catullus’ lament for his brother in carmen 101 as he describes Nemesis’ dead young sister and demonstrates his technical skill in manipulating the flexibility of grammatical gender in Latin

Interface for Physics Simulation Engines

DSS-Prototyper is an open-source, realtime 3D virtual environment software that supports design simulation for the new Vision for Space Exploration (VSE). This is a simulation of NASA's proposed Robotic Lunar Exploration Program, second mission (RLEP2). It simulates the Lunar Surface Access Module (LSAM), which is designed to carry up to four astronauts to the lunar surface for durations of a week or longer. This simulation shows the virtual vehicle making approaches and landings on a variety of lunar terrains. The physics of the descent engine thrust vector, production of dust, and the dynamics of the suspension are all modeled in this set of simulations. The RLEP2 simulations are drivable (by keyboard or joystick) virtual rovers with controls for speed and motor torque, and can be articulated into higher or lower centers of gravity (depending on driving hazards) to enable drill placement. Gravity also can be set to lunar, terrestrial, or zero-g. This software has been used to support NASA's Marshall Space Flight Center in simulations of proposed vehicles for robotically exploring the lunar surface for water ice, and could be used to model all other aspects of the VSE from the Ares launch vehicles and Crew Exploration Vehicle (CEV) to the International Space Station (ISS). This simulator may be installed and operated on any Windows PC with an installed 3D graphics card

Recent Work on Tibullus

This introduction provides an overview of Tibullus’ life, his poetry, and his style, and offers a bibliographical survey of emerging critical trends in interpreting this relatively neglected Roman elegist

[Introduction to] In the Flesh: Embodied Identities in Roman Elegy

In the Flesh deeply engages postmodern and new materialist feminist thought in close readings of three significant poets—Propertius, Tibullus, and Ovid—writing in the early years of Rome\u27s Augustan Principate. In their poems, they represent the flesh-and-blood body in both its integrity and vulnerability, as an index of social position along intersecting axes of sex, gender, status, and class. Erika Zimmermann Damer underscores the fluid, dynamic, and contingent nature of identities in Roman elegy, in response to a period of rapid legal, political, and social change.Recognizing this power of material flesh to shape elegiac poetry, she asserts, grants figures at the margins of this poetic discourse—mistresses, rivals, enslaved characters, overlooked members of households—their own identities, even when they do not speak. She demonstrates how the three poets create a prominent aesthetic of corporeal abjection and imperfection, associating the body as much with blood, wounds, and corporeal disintegration as with elegance, refinement, and sensuality.https://scholarship.richmond.edu/bookshelf/1341/thumbnail.jp

SynthASpoof: Developing Face Presentation Attack Detection Based on Privacy-friendly Synthetic Data

Recently, significant progress has been made in face presentation attack detection (PAD), which aims to secure face recognition systems against presentation attacks, owing to the availability of several face PAD datasets. However, all available datasets are based on privacy and legally-sensitive authentic biometric data with a limited number of subjects. To target these legal and technical challenges, this work presents the first synthetic-based face PAD dataset, named SynthASpoof, as a large-scale PAD development dataset. The bona fide samples in SynthASpoof are synthetically generated and the attack samples are collected by presenting such synthetic data to capture systems in a real attack scenario. The experimental results demonstrate the feasibility of using SynthASpoof for the development of face PAD. Moreover, we boost the performance of such a solution by incorporating the domain generalization tool MixStyle into the PAD solutions. Additionally, we showed the viability of using synthetic data as a supplement to enrich the diversity of limited authentic training data and consistently enhance PAD performances. The SynthASpoof dataset, containing 25,000 bona fide and 78,800 attack samples, the implementation, and the pre-trained weights are made publicly available.Comment: Accepted at CVPR workshop 202

Optimization-Based Improvement of Face Image Quality Assessment Techniques

Contemporary face recognition (FR) models achieve near-ideal recognition performance in constrained settings, yet do not fully translate the performance to unconstrained (realworld) scenarios. To help improve the performance and stability of FR systems in such unconstrained settings, face image quality assessment (FIQA) techniques try to infer sample-quality information from the input face images that can aid with the recognition process. While existing FIQA techniques are able to efficiently capture the differences between high and low quality images, they typically cannot fully distinguish between images of similar quality, leading to lower performance in many scenarios. To address this issue, we present in this paper a supervised quality-label optimization approach, aimed at improving the performance of existing FIQA techniques. The developed optimization procedure infuses additional information (computed with a selected FR model) into the initial quality scores generated with a given FIQA technique to produce better estimates of the "actual" image quality. We evaluate the proposed approach in comprehensive experiments with six state-of-the-art FIQA approaches (CR-FIQA, FaceQAN, SER-FIQ, PCNet, MagFace, SDD-FIQA) on five commonly used benchmarks (LFW, CFPFP, CPLFW, CALFW, XQLFW) using three targeted FR models (ArcFace, ElasticFace, CurricularFace) with highly encouraging results.Comment: In proceedings of the International Workshop on Biometrics and Forensics (IWBF) 202