$\beta\sb2$-Adrenoceptor ($\beta\sb2$-AR) agonists, such as terbutaline, are used as tocolytic agents in the treatment of preterm labor. $\beta$-Adrenoceptor stimulation relaxes myometrium through specific receptors coupled through Gs to adenylyl cyclase (AC) that catalyzes the conversion of ATP to cAMP. The purpose of this study was to compare $\beta$-adrenoceptors and cAMP production in cultured human leukocytes and myometrial cells, and to determine the importance of $\beta$-adrenoceptors and cAMP production in isoproterenol-induced myometrial relaxation. $\sp{125}$I-iodopindolol was used to assess $\beta$-adrenoceptor affinity and number cAMP levels were analyzed before and after stimulation by isoproterenol, AlF$\sb4\sp-$, forskolin, and PGE$\sb1$. Isometric recording was used to examine myometrium contraction and relaxation. $\beta$-adrenoceptors in leukocytes and myometrial cells have similar $\sp{125}$I-iodopindolol binding affinity and B$\rm\sb{MAX}$. Both tissues can be stimulated by isoproterenol, but have reserve adenylyl cyclase activity not stimulated by $\beta$-ARs. Cultured human myometrial cells have higher basal AC activity and lower isoproterenol coupled cAMP production than leukocytes. The rank order of $\beta$-adrenoceptor agonist potencies in leukocytes is: isoproterenol $>$ terbutaline $>$ ritodrine. Myometrial cells could not be stimulated by terbutaline or ritodrine. This indicates that the intrinsic activity of $\beta$-adrenoceptor coupled cAMP production is different in these two tissues. Prolonged exposure to 200 nM terbutaline results in a decrease in both $\beta$-adrenoceptor number and isoproterenol-coupled cAMP production in cultured leukocytes and myometrial cells. Signal transduction factors, such as adenylyl cyclase and the PGE$\sb1$ pathway, are not affected by the down-regulation process. Isoproterenol relaxes term myometrium through $\beta\sb2$-ARs without a change in cAMP production. Cultured leukocytes do not completely reflect the activity of $\beta$-adrenoceptor coupled cAMP production to myometrial cultured cells. In myometrium, the presence of $\beta$-ARs does not guarantee stimulation of cAMP production, and cAMP is not an accurate index of myometrial relaxation at the end of pregnancy. While leukocytes may accurately reflect changes in myometrial $\beta$-adrenoceptors, postreceptor differences suggest that they are not a reasonable indicator of myometrial response to $\beta$-AR stimulation.

Although we give library instruction in graduate courses per request,we reach a small number of students this way. Others will see us oneon-one,but we’re still missing the majority. Nearly all Boot Campersare unknown to us, which means they’ve had no formal graduatelibrary instruction prior to writing the biggest project of their academiclives.To this end, we offered two new strategy-based workshops, whichwe propose to outline as one single-session presentation at USETDAunder the category of “Student Support and Training” (ImpactfulETD Processing).In Boot Camp, Session One covers data management: physical andvirtual workspace organization, file structure, online data storage andbackups. The emphasis here is on where to put data and how to saveit. Online programs covered include free word processing softwaresuch as Google Docs, Word Online, Shutterbug, and Zoho Docs andcloud storage services such as Google Drive, Microsoft’s OneDrive,Mac’s iCloud Storage, Amazon storage, Box and Dropbox.Session Two of Boot Camp addresses research and citation management.Revamped to include the Association of College and ResearchLibraries (ACRL) Information Literacy Framework’s concepts, wepresent systematic research as a transferable skill, not an isolated casetied to one course or problem. This workshop incorporates criticalthinking into showing students how to construct a search; how tokeep on top of research through folders, feeds, and alerts; and how tomanage citations via Mendeley.After the presentation and discussion, attendees should be able torecognize the significant function librarians perform in a targetedprogram such as Boot Camp convey the value of formal, timelyintervention for graduate students assess the benefits of linking ouroverall methodology to the ACRL Framework replicate our offeringsto support their students at the point of need, and beyond.

Chronic postoperative pain impacts millions of individuals worldwide that undergo a variety of surgical procedures. Opioids remain the mainstay analgesics of acute and perioperative pain; however, prolonged opioid therapy may lead to life-threating adverse effects, tolerance, dependence, and addiction. Therefore, unraveling the cellular mechanisms that drive persistent pain states and opposing endogenous analgesia provided by opioid receptor signaling, may lead to novel analgesics. Evidence suggests that tissue injury leads to increased sensitization of the spinal cord nociceptive neurons which increases susceptibility to chronic pain via an N-methyl-D-aspartate (NMDA) receptor activation of calcium-sensitive adenylyl cyclase isoform 1 (AC1). This phenomenon, named latent pain sensitization (LS), is mediated by a compensatory response of endogenous inhibitory systems. In this dissertation, we test the hypothesis that surgical insult promotes prolonged activation of kappa opioid receptors (KOR) which mask LS via attenuation of pro-nociceptive AC1 signaling pathways in both male and female animals. We employed a murine model of chronic postoperative pain that promotes LS in the spinal cord and closely resembles the phenotypic features of postoperative pain in human subjects. When behavioral signs of hyperalgesia resolved, we targeted spinal opioid receptor systems and pronociceptive modulators with intrathecal delivery of selective pharmacological antagonists and assessed behavioral signs of hyperalgesia and spinal nociceptive sensitization. We propose that LS is kept in remission by a long-lasting compensatory response of tonic endogenous KOR signaling that hinders a pronociceptive LS pathway that includes not only AC1 but also two downstream targets: protein kinase A (PKA) and exchange protein activated by cAMP (Epac1/2) - in a sex-dependent manner. Our results propose new therapeutic targets for the management of persistent postoperative pain and underscore the importance of tailoring sex-specific pain management strategies.

Hyperpolarization-activated, cyclic-nucleotide gated ion channels (HCN channels) are activated by membrane hyperpolarization and modulated by cyclic nucleotides. HCN channels are important to maintain the resting membrane potential and input resistance in neurons and have important physiological functions in the brain and heart. Four mammalian HCN isoforms, HCN1-4, and the isoform cloned from sea urchin, spHCN, have been extensively studied. Among these, only spHCN channel shows a voltage dependent inactivation. Previous studies have shown that the ligand binding in mHCN2 channel is activity dependent: cAMP binding increases along with channel opening or channels in the open state have higher binding affinity for cAMP. But to date, information pertaining to the ligand binding to an inactivated ion channel or desensitized receptor is lacking. To address this gap, we used fluorescently labelled cAMP analogues in conjunction with patch clamp fluorometry (PCF) to study the ligand binding to the spHCN channel in various conformational states. We show that inactivated spHCN channel shows reduced binding affinity for cAMP, compared to that of the closed or open channel. Parallelly, we noticed significant changes to channel function when a combination of laser and photosensitizer was used to study ligand binding. A reactive oxygen species called singlet oxygen has been confirmed to be the major player in this process. Both photo-dynamically generated and chemically generated singlet oxygen modifies spHCN channel by removing the inactivation. The effect of singlet oxygen on channel can be abolished by the mutation of a key histidine (H462) residue in the ion conducting pore. Taken together, these two projects expanded our understanding about the physicochemical nature of fluorophores from two aspects: (i) the release of photon as a valuable tool to study the conformational dynamics in proteins; (ii) the generation of singlet oxygen as an effective modulator of protein function.

Hériter d’un récit inédit d’expérience concentrationnaire revient à accepter le devoir moral de l’interpréter. Le comparer avec deux œuvres littérairement consacrées portant sur le même thème permet alors de réfléchir sur l’inéluctable transformation que subit un vécu traumatisant lorsque l’on tente de le verbaliser. Il s’agit en effet de dire et de transmettre une aporie. C’est pourquoi le recours réussi à la métaphore apparaît comme le moyen le plus efficace de doter ce morceau de vie par nature indicible d’une rhétorique convaincante. Par conséquent, il faut transposer le vécu pour parvenir à le dire, mais aussi donner à voir un passé qui ne remonte à la conscience qu’en images, tout en affirmant ses références à un réel inscrit dans l’Histoire. Pour faire aboutir une telle entreprise, il s’agit donc d’élaborer une fiction à partir d’une réalité vécue, de la doter d’un mode d’écriture au pouvoir visualisant, et enfin d’y introduire une dialectique interne susceptible de déclencher chez le lecteur une réflexion éthique. En effet, la vérité du témoignage reste tributaire d’une identité qui ne se construit qu’à l’occasion de la mise en récit. De plus, le texte est confectionné au présent et à partir de simples traces mémorielles. Enfin même si l’historiographie en valide les références, il en demeure une part obscure qui échappera toujours au langage articulé. Ce questionnement sur ce qui peut donner au témoignage concentrationnaire sa force d’impact conduit ainsi à suggérer que, le camp ayant été vécu comme expérience de la défiguration, seule son inscription dans une poétique de l’incarnation susceptible de rendre à la lettre morte sa puissance explosive aidera le rescapé à reconquérir un visage. / Inheriting the unpublished story of a concentration camp experience implies accepting the moral duty of its interpretation. Comparing it with two others literary works on the same topic allows to build a reflection about the inevitable transformation undergone by a traumatic experience when you attempt to verbalize it. In effect, that comes down to say and convey an aporia. That is why resorting successfully to metaphor seems to be the most efficient way to endow this piece of life, unspeakable by itself, with a convincing rhetoric. Therefore, it is necessary to transpose the experience in order to manage to tell it, but also to make visible a past that comes back to conscience only in the form of pictures, while asserting its references to a reality inscribed into History. To succeed in such an attempt, the method consists first in elaborating a fiction from a lived reality, then in giving its writing a power of visualisation, and eventually in introducing into it an internal dialectic capable of causing in the reader the uprising of an ethical reflection. In fact, the truth of any testimony remains tributary of an identity that is built only at the occasion of a storytelling. Moreover, the text is written in the present and from mere memorial marks. Finally, even when History gives validation to its references, a dark part remains, which will always escape the articulated language. This questionning about what may give the concentration camp experience its strenght of impact then leads to suggest that, since the camp has been lived as an experimentation of defiguration, it is only by inscribing it into a poetic of incarnation, capable of restituting to the dead letter its explosive power, that the survivor will be able to reconquer a human face.

Utilising a critical theoretical perspective, this work examines contemporary corporatised tourism and capitalist globalisation. This analysis suggests that marketisation limits the understanding of the purposes of tourism to its commercial and “industrial” features, thereby marginalising wider understandings of the social importance of tourism. Sklair’s conceptualisation of capitalist globalisation and its dynamics, as expressed in his “sociology of the global system” (2002), is employed to understand the corporatised tourism phenomenon. This thesis explains how a corporatised tourism sector has been created by transnational tourism and travel corporations, professionals in the travel and tourism sector, transnational practices such as the liberalisation being imposed through the General Agreement on Trade in Services negotiations and the culture-ideology of consumerism that tourists have adopted. This thesis argues that this reaps profits for industry and exclusive holidays for privileged tourists, but generates social and ecological costs which inspire vigorous challenge and resistance. This challenge is most clearly evident in the alternative tourism movement which seeks to provide the equity and environmental sustainability undermined by the dynamics of corporatised tourism. Alternative tourism niches with a capacity to foster an “eco-humanism” are examined by focusing on ecotourism, sustainable tourism, pro-poor tourism, fair trade in tourism, community-based tourism, peace through tourism, volunteer tourism and justice tourism. While each of these demonstrates certain transformative capacities, some prove to be mild reformist efforts and others promise more significant transformative capacity. In particular, the niches of volunteer tourism and justice tourism demonstrate capacities to mount a vigorous challenge to both corporatised tourism and capitalist globalisation. Since the formation of the Global Tourism Interventions Forum (GTIF) at the World Social Forum gathering in Mumbai in 2004, justice tourism has an agenda focused on overturning corporatised tourism and capitalist globalisation, and inaugurating a new alternative globalisation which is both “pro-people” and sustainable. Following the development of these original, macro-level conceptualisations of tourism and globalisation, this thesis presents a micro-level case study of an Indigenous Australian tourism enterprise which illustrates some of these dynamics in a local context. Camp Coorong Race Relations and Cultural Education Centre established and run by the Ngarrindjeri Aboriginal community of South Australia has utilised tourism to foster greater equity and sustainability by working towards reconciliation through tourism. The Ngarrindjeri have also experienced conflicts generated from the pressures of inappropriate tourism development which has necessitated an additional strategy of asserting their Indigenous rights in order to secure Ngarrindjeri lifeways. The case study analysis suggests that for alternative tourism to create the transformations that contemporary circumstances require, significant political change may be necessary. This includes fulfilment of economic, social and cultural rights to which a majority of nations have committed but have to date failed to implement. While this is a challenge for nation-states and is beyond the capacities of tourism alone, tourism nonetheless can be geared toward greater equity and sustainability if the perspective that corporatised tourism is the only option is resisted. This thesis demonstrates that another tourism is possible; one that is geared to public welfare, human fulfilment, solidarity and ecological living.

<p>The governor collections at the Colorado State Archives are a rich source for research and information about social science and the history of the state, but they are not always easy to research due to their differences in taxonomy through different eras. In my work with creating an archival research handbook for a governor collection I chose governor Ralph Carr to both illustrate the challenges as well as the thrills with historical research in a collection from the office of the governor.</p><p>Ralph Carr's collection takes patience to research. Some series will have inconsistent taxonomy and other series lack sub-series, and if a researcher is not familiar with the terminology of state affairs, many documents can pose a challenge. It is my hope that this handbook will be of use for both amateur researchers as well as provide a few short-cuts for more seasoned scholars. Governor Carr's collection covers some of the most dramatic years in Colorado history, the first part of WWII, and it is frequently requested for research, but many researchers get stuck between the vast amount of documents only sorted by dates, for instance in the series marked "Council of Defense", which contains many interesting documents about the Japanese-Americans who were to be deported to the Granada Relocation camp, or Camp Amache, as it was popularly called. It is my hope that the guide will not only provide such researchers some relief, but also to get the reader a sense for Colorado History, The Colorado State Archives and for the Governor collections in general.</p>

Flüssigkeitssekretion und Proteinsekretion werden in Speicheldrüsen von Insekten über Hormone und Neurotransmitter gesteuert. Diese entfalten ihre physiologische Wirkung in den sekretorischen Drüsenzellen hauptsächlich über den zyklischen Adenosinmonophosphat (cAMP)-Signalweg und den Inositoltrisphosphat (IP<SUB>3</SUB>) / Ca²⁺-Signalweg. Die Mechanismen möglicher Wechselwirkungen zwischen diesen Signalwegen und ihre physiologischen Auswirkungen sind unzureichend bekannt.<p> Im Mittelpunkt dieser Arbeit stand die Frage, ob und wie sich der Ca²⁺-Signalweg und der cAMP-Signalweg in der Speicheldrüse der Diptere <I>Calliphora vicina</I> beeinflussen. Substanzen wie 5-Fluoro-α-Methyltryptamin und Histamin wurden in früheren Arbei-ten als Agonisten genutzt, um in den Speicheldrüsen von <I>C. vicina</I> selektiv den cAMP-Signalweg (getrennt vom IP<SUB>3</SUB>/Ca²⁺-Signalweg) zu aktivieren. Es zeigte sich in transepithelialen Potentialmessungen und mikrofluorometrischen Ca²⁺-Untersuchungen, dass beide Substanzen sowohl den cAMP-Weg als auch den Ca²⁺-Signalweg aktivierten. Die physiologischen Ursachen der Histamin-induzierten Ca²⁺-Erhöhung wurden genauer untersucht. <p> Zusammengefasst zeigten diese Untersuchungen, dass Histamin wie 5-HT den cAMP-Weg und die Phosphoinositidkaskade aktivierte. Im Gegensatz zu den 5-HT-induzierten Ca²⁺-Oszillationen, welche durch interzelluläre Ca²⁺-Wellen synchronisiert werden, verursachte Histamin bei niedrigen Konzentrationen lokale Ca²⁺-Oszillationen in einzelnen Zellen (keine Wellen). Bei höheren Histamin-Konzentrationen war eine anhaltende Ca²⁺-Erhöhung oder ein synchrones <quote>Ca²⁺-beating</quote> in der gesamten Drüse zu beobachten. <p> Des Weiteren wurde die Frage untersucht, ob eine Erhöhung der intrazellulären cAMP-Konzentration den IP<SUB>3</SUB> Ca²⁺-Signalweg in den Epithelzellen der Speicheldrüse beeinflussen kann. Es zeigte sich, dass cAMP den durch schwellennahe 5-HT-Konzentrationen induzierten Ca²⁺-Anstieg verstärkte. Diese Verstärkung wurde durch eine PKA-vermittelte Sensitivierung des IP<SUB>3</SUB>-Rezeptor/Ca²⁺-Kanals für IP<SUB>3</SUB> verursacht. Immunzytochemische Untersuchungen deuten dar-auf hin, dass die Proteinkinase A eng mit dem IP<SUB>3</SUB>-Rezeptor/Ca²⁺-Kanal assoziiert ist. Diese Messungen zeigen erstmals, dass auch bei Invertebraten der Botenstoff cAMP, PKA-vermittelt, den IP<SUB>3</SUB>-Rezeptor/Ca²⁺-Kanal des ER für IP<SUB>3</SUB> sensitiviert. / Fluid- and protein-secretion in the salivary glands of insects are controlled by hormones or neurotransmitters. These agonists activate two signalling cascades: the cAMP-pathway and the IP>sub>3</sub>/Ca-pathway. The functional crosstalk between these two signalling pathways is poorly understood. <p> Functional crosstalk between cAMP-pathway and IP₃/Ca²⁺-pathway was investigated in the salivary glands of the blowfly, <I>Calliphora vicina</I>. Histamine and 5-alpha-methyltryptamine were used in an attempt to activate the cAMP-pathway selectively, as suggested previously. By using transepithelial potential-measurements and microfluorometric Ca²⁺-imaging it was demonstrated that both substances activate the cAMP- and the IP₃/Ca²⁺-pathway. The physiological effects of histamine were investigated in detail. These experiments show that histamine causes an intracellular Ca²⁺-elevation that, in some preparations exhibits oscillations with concentration-dependent frequencies. In contrast to 5-HT induced intracellular Ca²⁺-oscillations and propagating intercellular Ca²⁺-waves histamine produces local Ca²⁺-oscillations in single cells or synchronous <quote>Ca²⁺-beating</quote> in the whole gland.<p> In addition the effects of increasing cAMP on the IP₃/Ca²⁺-pathway in the salivary glands of the blowfly were studied. It could be demonstrated that cAMP augments the 5-HT-induced Ca²⁺-increase in glands stimulated with low doses of 5-HT. This potentiation is the result of a PKA-mediated sensitisation of the IP₃-receptor/Ca²⁺-channel for IP₃. Results of immunocytochemical analyses show that the PKA is spatially associated with the ER.<p> These results show for the first time that in invertebrates as well as in vertebrates the second messenger cAMP sensitises the IP₃-receptor/Ca²⁺-channel for IP₃ by the action of a PKA.

The governor collections at the Colorado State Archives are a rich source for research and information about social science and the history of the state, but they are not always easy to research due to their differences in taxonomy through different eras. In my work with creating an archival research handbook for a governor collection I chose governor Ralph Carr to both illustrate the challenges as well as the thrills with historical research in a collection from the office of the governor. Ralph Carr's collection takes patience to research. Some series will have inconsistent taxonomy and other series lack sub-series, and if a researcher is not familiar with the terminology of state affairs, many documents can pose a challenge. It is my hope that this handbook will be of use for both amateur researchers as well as provide a few short-cuts for more seasoned scholars. Governor Carr's collection covers some of the most dramatic years in Colorado history, the first part of WWII, and it is frequently requested for research, but many researchers get stuck between the vast amount of documents only sorted by dates, for instance in the series marked "Council of Defense", which contains many interesting documents about the Japanese-Americans who were to be deported to the Granada Relocation camp, or Camp Amache, as it was popularly called. It is my hope that the guide will not only provide such researchers some relief, but also to get the reader a sense for Colorado History, The Colorado State Archives and for the Governor collections in general.

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