7,708 research outputs found
Drugs Affecting 5-HT Systems
No full textSeminar transcriptIt was in the very early hours of a February morning in 1977 that I first looked down the microscope and saw yellow fluorescence, characteristic of 5-hydroxytryptamine (5-HT) in frozen sections of Octopus brain. After struggling for two years with the capricious fluorescence histochemical technique to locate catecholamines and 5-HT, I finally had a successful result, and the PhD that had seemed a remote possibility for many months finally began to look feasible. Given the enormously important topic of this volume – the discovery and development of drugs affecting 5-HT systems – this small excursion into Octopus neurochemistry might seem irrelevant. However, cephalopod molluscs have played important roles in the history of 5-HT. More than 30000 pairs of posterior salivary glands of Octopus vulgaris were used by Vittorio Erspamer, for the first extraction and identification of enteramine, which was later shown to be identical to serotonin discovered by John Gaddum, and chemically characterized as 5-hydroxytryptamine. Other molluscs have provided some of the most sensitive bioassays for 5-HT, as Gaddum and Paasonen described in 1955, and several participants in this Witness Seminar recollected either using such bioassays or investigating invertebrate pharmacology at the beginning of their careers. Many reflected, however, that invertebrate receptors seemed to be very different from those found in mammals; they had, as David Wallis put it, ‘a parallel pharmacology’. One Witness, Merton Sandler, remembered attending a lecture by Vittorio Erspamer in London in the early 1950s, and being intrigued enough to start work on the degradative enzyme monoamine oxidase, a field which became highly significant for the development of a whole class of therapeutic drugs: the monoamine oxidase inhibitor
5-ht inhibition of rat insulin 2 promoter cre recombinase transgene and proopiomelanocortin neuron excitability in the mouse arcuate nucleus
No full textA number of anti-obesity agents have been developed that enhance hypothalamic 5-HT transmission. Various studies have demonstrated that arcuate neurons, which express proopiomelanocortin peptides (POMC neurons), and neuropeptide Y with agouti-related protein (NPY/AgRP) neurons, are components of the hypothalamic circuits responsible for energy homeostasis. An additional arcuate neuron population, rat insulin 2 promoter Cre recombinase transgene (RIPCre) neurons, has recently been implicated in hypothalamic melanocortin circuits involved in energy balance. It is currently unclear how 5-HT modifies neuron excitability in these local arcuate neuronal circuits. We show that 5-HT alters the excitability of the majority of mouse arcuate RIPCre neurons, by either hyperpolarization and inhibition or depolarization and excitation. RIPCre neurons sensitive to 5-HT, predominantly exhibit hyperpolarization and pharmacological studies indicate that inhibition of neuronal firing is likely to be through 5-HT1F receptors increasing current through a voltage-dependent potassium conductance. Indeed, 5-HT1F receptor immunoreactivity co-localizes with RIPCre green fluorescent protein expression. A minority population of POMC neurons also respond to 5-HT by hyperpolarization, and this appears to be mediated by the same receptor-channel mechanism. As neither POMC nor RIPCre neuronal populations display a common electrical response to 5-HT, this may indicate that sub-divisions of POMC and RIPCre neurons exist, perhaps serving different outputs. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.</p
Hamiltonian Truncation in Quantum Mechanics and Quantum Field Theory
No full textQuantum mechanics and quantum field theory are fundamental frameworks of modern theoretical physics. Since their development in the early 20th century, physicists have long taken endeavors to use those frameworks to better describe our known physical universe. Many theories have been proposed and are awaiting confirmation, but their complex mathematical structures have hindered quick comparison with experiments. Thus a new movement in theoretical physics was embarked on, to develop methods to study complicated theories more accurately and faster and to yield accurate theoretical predictions to be directly tested against experimental data. Hamiltonian truncation (HT) is a product of this crucial movement and a methodology developed to complement more traditional methods used in quantum mechanics and quantum field theory. This Thesis is an exploration of this relatively new method and an attempt to apply this method to the study of scattering processes, for which it has been rarely employed to this date. This Thesis focuses on implementing HT in quantum mechanics, specifically, in onedimensional quantum mechanics and two-dimensional supersymmetric quantum mechanics. Following the procedure developed by Balthazar et al. [1], we numerically compute Hamiltonian matrices and use their eigenvalues to approximate scattering phase functions. We then analyze the spectrum, decay width, and lifetime of metastable states (resonances) and assess the effectiveness of HT in terms of the parameter L, the IR cutoff. For supersymmetric quantum mechanics, we confirm that our implementation of HT successfully reproduces the results by Balthazar et al. [1]. This Thesis lays the groundwork for future projects on HT that aim to implement the method in various quantum systems and to study more sophisticated scattering processes such as large multiparticle production in scalar quantum field theory
Green citizenship and the social economy
No full textContemporary green political theory has paid little attention to the role that economic organisations can play in the cultivation and expression of green citizenship. This paper argues that the ethos and structure of organisations within the social economy – for example, cooperatives, mutuals and voluntary associations – appear particularly well suited for the development of relevant dispositions, skills and capacities. The associative reform of both the welfare state and the for-private-profit economy therefore offers a challenging and creative strategy for enhancing green citizenship
Survey article. Democratic innovations: bringing theory and practice into dialogue
No full textIn recent years there has been an ‘institutional turn’ in democratic theory. This survey article focuses on a broad family of institutions: democratic innovations which aim to increase and deepen citizen participation in the political decision-making process. Attention to the design of democratic innovations is of value to the development of both democratic theory and practice
Youthhood
No full textTESTING-GROUND issue 03, Youthhood, examines worlds through youthful eyes, makes evident young ambitions, and questions how we can better empower young people to design cities, landscapes, and a planet that works for them. The issue includes contributions from: Carmel Keren, Jude Daniel Smith, Claire Edwards, Kazeem Kuteyi, Emmanuel Adarkwah, Reza Nik, Dan Cui, Kristofer Cullum-Fernandez, Fida Sassi, Simeon Shtebunaev, Daze Aghaji, Averill Dimabuyu, Sarri Elfaitouri, Rebecca McDonald-Balfour, and Ed Wall.
Rebecca McDonald-Balfour (Author), Jude Daniel Smith (Author), Daze Aghaji (Author), Carmel Keran (Author), Alexis Liu (Author), Dan Cui (Author), Kristofer Cullum-Fernandez (Author), Fida Sassi (Author), Averill Dimabuyu (Author), Ed
Dickens’s shorthand deciphered by identifying ‘Sydney Smith’ source text
No full textThis article describes how a Dickens shorthand text was deciphered and identified as a text by Sydney Smith which he used as a dictation exercise for one of the shorthand lessons he was giving to Arthur Stone in 1859-60
Power relations, industrial clusters and regional transformations: pan-European integration and outward processing in the Slovak clothing industry
No full textSince the late 1980s the East European clothing sector has witnessed a dramatic transformation. Driven by increasing costs in Western Europe, Western clothing retailers and buyers have increasingly outsourced production to lower-cost regions of postcommunist Eastern Europe. One consequence of these changes has been a dramatic growth of clothing producers in Eastern Europe, locked into supply relations with Western buyers while simultaneously involved in dense networks of relations between firms in regional clusters. This article focuses on the form that power relations take, which knit together pan-European supply linkages and regional clusters of clothing firms in Slovakia. In drawing on a weak form of actor-network theory and an understanding of capitalist commodity production, the article explores the uneven nature of these power relations, as well as their fluidity at three levels. First, attention is given to relations between Slovak firms and Western buyers that largely involve a tenuous form of price competitiveness, which is simultaneously under threat from lower-cost production zones elsewhere. Second, the variant power relations between producers in regional clusters of clothing firms in Slovakia are explored. Production flexibilities have been built through a network of locally agglomerated workshop production units and domestic home-based workers to whom work is outsourced when required. Third, the implications of these forms of outsourcing are explored in relation to workplace and wage-level pressures. The article therefore suggests the importance of understanding dynamic and fluid power relations in the economic geography of regional clusters and the globalization of outsourcing in the clothing sector
Democratic innovations: designing institutions for citizen participation
No full textCan we design institutions that increase and deepen citizen participation in the political decision making process? At a time when there is growing disillusionment with the institutions of advanced industrial democracies, there is also increasing interest in new ways of involving citizens in the political decisions that affect their lives. This book draws together evidence from a variety of democratic innovations from around the world, including participatory budgeting in Brazil, Citizens’ Assemblies on Electoral Reform in Canada, direct legislation in California and Switzerland and emerging experiments in e-democracy. The book offers a rare systematic analysis of this diverse range of democratic innovations, drawing lessons for the future development of both democratic theory and practice
Different effects of single and fractionated light delivery regimes in photodynamic therapy with hypericin on HT-29 cells in vitro
No full textPhotodynamic therapy (PDT) is an alternative cancer cure which involves the selective uptake and retention of a photosensitizer in a cancer tissue, followed by irradiation with light of a specific wavelength to kill tumour cells via the production of reactive oxygen species (ROS). Fractionation of the light administration is one of the protocol modifications in PDT based on the hypothesis of tissue reoxygenation during the one or more dark intervals between illuminations with a subsequent greater production of singlet oxygen and thus greater PDT effect. However we demonstrate in the present study that two-fold illumination scheme with equal light doses (3 or 6 J.cm-2) separated by a dark interval 1 or 6 h do not enhanced, even reduced hypericin-mediated photocytotoxic effect in HT-29 adenocarcinoma cells in vitro by illumination with unequal light doses (1 + 11 J.cm-2) separated with a longer dark pause (6 h). Fractionation with a longer dark pause increased cell number and cell survival in HT-29 cells when compared with such treatment but with a 1 h dark pause or with a single light delivery (12 J.cm-2). Even proportion of cells in G1 and G2 phase of cell cycle were near to control. Longer dark pause also repressed cell death and enhanced clonogenic potential of HT-29 cells. Since longer dark interval after the irradiation by first sub-lethal light dose (1 J.cm-2) makes cells resistant to the effect of the lethal light dose (11 J.cm-2), we studied the events proceeded during a dark pause after sub-lethal dose (1 J.cm-2) up to the second illumination. We show that pre-sensitization did not affect physiological elimination of hypericin however administration regime affected hypericin elimination after lethal dose. Inhibition of p38 MAPK did not improve photocytotoxic effect of light fractionation. Cell pre-sensitization induced ROS production, increased activity of redox-regulated nuclear transcription factor NF-κB and expression of proteins connected with a cell survival (NF-κB p50 and p65 subunits, IκB-α, Mcl-1, HSP70, GRP94, Clusterin-α). Although the role of heat shock proteins was generally established in response upon photo-induced stress, we uncovered that HSPs are not necessarily the “key” molecules in photo-resistance. Our findings indicate that timing of the second light dose before or after NF-κB activation could be crucial for the fate of cancer cell. We estimate successful application of hypericin in a high-dose multi-fraction PDT with dark intervals reduced bellow 1 h that might yield improved outcome
- …
