The Preemptive Paradox: The Rise of Great Powers & Management of the International System

Since the beginning of the modern state system only a few select nations have achieved great power status. But what can account for their rise? The presence of existing great powers would suggest that aspiring states should encounter formidable obstacles that would render their success implausible. In some cases extant great powers sought to counter the rise of a new peer, but the historical record also reveals that incumbents sometimes did not contest the rise of potential competitors. Thus, great powers have pursued two divergent strategies: contestation and nonintervention. How then do great powers decide on which policy to implement? This dissertation advances the argument that a great power’s military strategy is premised on its national interests. It argues that the reason incumbent powers rarely preempt the rise of aspiring powers is because of the low level of threat they pose to states. Incumbent great powers are far more concerned about contemporary rival powers since they possess the immediate capacity to undermine a state’s interests

Victory over Terrorism: Essential Services as Counterinsurgency Strategy

The preponderance of postsurge analysis is devoted to military operations and their subsequent efficacy in reducing levels of violence by concentrating on troop deployments, tactics, and intelligence. Such studies are valuable, but only to a certain extent. Any holistic appraisal must also consider noncombat counterinsurgency strategies that addressed social issues—in particular, essential services. Reminiscent of Lebanon’s Hizballah, militias in Baghdad sought ascendency over services as a means to solidify control and influence. Therefore, the most pragmatic remedy for long-term stability in Iraq was not necessarily countering militants with force, but securing the populace’s allegiance to their government through the provision of services and opportunities for employment... Emphasizing reconstruction projects not only improved the delivery of services, but also, more importantly, provided employment, reestablished the integrity of the Iraqi government, and created stakeholders in the overall process

WORK-FAMILY CONFLICT AND LIFE SATISFACTION IN FEMALE GRADUATE STUDENTS: TESTING MEDIATING AND MODERATING HYPOTHESES

Most of the research on work-family conflict has examined people working in the paid labor force while simultaneously juggling the roles of paid worker, partner, parent, and homemaker. There is limited research on female graduate students and their experiences of work-family conflict. The goals of the present study were to examine the relationship between work-family conflict (work-to-family conflict and family-to-work conflict) and global life satisfaction, the relationship between work-family conflict and domain-specific satisfactions (family satisfaction and work satisfaction), and the mediators and moderators of these relationships among a sample of female graduate students. Participants included 187 female graduate students. Both work-to-family conflict and family-to-work conflict were hypothesized to be negatively related to domain-specific and global life satisfactions. Work/family conflict self-efficacy and perceived social support were hypothesized to be positively related to domain-specific and global life satisfactions. Neuroticism was hypothesized to be negatively related to domain-specific and global life satisfactions, whereas extraversion was hypothesized to be positively related to domain-specific and global satisfactions. These hypothesized relationships were significant except the positive relationships of extraversion to family, work, and global life satisfactions. It was also predicted that domain-specific satisfactions would mediate the relationships between work-to-family conflict and global life satisfaction, and between family-to-work conflict and global life satisfaction. Work/family conflict self-efficacy and perceived social support were hypothesized to moderate the relationships between work-to-family conflict and domain-specific satisfactions, and between family-to-work conflict and domain-specific satisfactions. Results suggested family satisfaction and work satisfaction partially mediated the relationships between work-to-family conflict and global life satisfaction, and between family-to-work conflict and global life satisfaction. Work/family conflict self-efficacy moderated both the relationship between work-to-family conflict and work satisfaction, and between family-to-work conflict and work satisfaction. No other significant moderators were found. Implications for research and practice, and limitations of the present study are discussed

Ethanol directly modulates gating of a dihydropyridine-sensitive Ca2+ channel in neurohypophysial terminals

Ingestion of ethanol results in a decreased level of plasma vasopressin, which appears to be caused by inhibition of arginine vasopressin (AVP) release from the neurohypophysis. Activation of membrane voltage-gated Ca2+ channels plays an important role in triggering this neurohormone release. In this article, single-channel recordings are used to demonstrate that ethanol, at concentrations constituting legal intoxication, inhibits dihydropyridine-sensitive L-type Ca2+ channels in isolated nerve terminals of the rat neurohypophysis. Ethanol reduced the channel open probability in a concentration-dependent manner. To allow finer resolution of channel openings and to better characterize the mechanisms of ethanol action, Bay K 8644 was used to prolong the openings of L-type Ca2+ channels. In the presence of this dihydropyridine (DHP), the reduction of the channel open probability by concentrations of ethanol of 25 mM or higher could be determined to be due primarily, although not completely, to a shortening of the open duration of this L-channel. Channel conductance was unaffected by ethanol, even at high concentrations. These results are consistent with previous macroscopic data indicating that calcium channels in these peptidergic terminals are targets for ethanol action, and indicate that ethanol acts directly on the gating characteristics of the L-type channel. Furthermore, examination of open and closed state transitions, as well as Hill plot analysis, suggests that ethanol\u27s effects on gating are consistent with the interaction of a single drug molecule with a single target site, possibly the L-channel itself

Large conductance voltage- and Ca2+-gated potassium (BK) channel beta4 subunit influences sensitivity and tolerance to alcohol by altering its response to kinases

Tolerance is a well described component of alcohol abuse and addiction. The large conductance voltage- and Ca(2+)-gated potassium channel (BK) has been very useful for studying molecular tolerance. The influence of association with the beta4 subunit can be observed at the level of individual channels, action potentials in brain slices, and finally, drinking behavior in the mouse. Previously, we showed that 50 mm alcohol increases both alpha and alphabeta4 BK channel open probability, but only alpha BK develops acute tolerance to this effect. Currently, we explore the possibility that the influence of the beta4 subunit on tolerance may result from a striking effect of beta4 on kinase modulation of the BK channel. We examine the influence of the beta4 subunit on PKA, CaMKII, and phosphatase modulation of channel activity, and on molecular tolerance to alcohol. We record from human BK channels heterologously expressed in HEK 293 cells composed of its core subunit, alpha alone (Insertless), or co-expressed with the beta4 BK auxiliary subunit, as well as, acutely dissociated nucleus accumbens neurons using the cell-attached patch clamp configuration. Our results indicate that BK channels are strongly modulated by activation of specific kinases (PKA and CaMKII) and phosphatases. The presence of the beta4 subunit greatly influences this modulation, allowing a variety of outcomes for BK channel activity in response to acute alcohol

Cholesterol Tuning of BK Ethanol Response Is Enantioselective, and Is a Function of Accompanying Lipids

In the search to uncover ethanol's molecular mechanisms, the calcium and voltage activated, large conductance potassium channel (BK) has emerged as an important molecule. We examine how cholesterol content in bilayers of 1,2-dioleoyl-3-phosphatidylethanolamine (DOPE)/sphingomyelin (SPM) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine (POPE)/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylserine (POPS) affect the function and ethanol sensitivity of BK. In addition, we examine how manipulation of cholesterol in biological membranes modulates ethanol's actions on BK. We report that cholesterol levels regulate the change in BK channel open probability elicited by 50 mM ethanol. Low levels of cholesterol (<20%, molar ratio) supports ethanol activation, while high levels of cholesterol leads to ethanol inhibition of BK. To determine if cholesterol affects BK and its sensitivity to ethanol through a direct cholesterol-protein interaction or via an indirect action on the lipid bilayer, we used the synthetic enantiomer of cholesterol (ent-CHS). We found that 20% and 40% ent-CHS had little effect on the ethanol sensitivity of BK, when compared with the same concentration of nat-CHS. We accessed the effects of ent-CHS and nat-CHS on the molecular organization of DOPE/SPM monolayers at the air/water interface. The isotherm data showed that ent-CHS condensed DOPE/SPM monolayer equivalently to nat-CHS at a 20% concentration, but slightly less at a 40% concentration. Atomic force microscopy (AFM) images of DOPE/SPM membranes in the presence of ent-CHS or nat-CHS prepared with LB technique or vesicle deposition showed no significant difference in topographies, supporting the interpretation that the differences in actions of nat-CHS and ent-CHS on BK channel are not likely from a generalized action on bilayers. We conclude that membrane cholesterol influences ethanol's modulation of BK in a complex manner, including an interaction with the channel protein. Finally, our results suggest that an understanding of membrane protein function and modulation is impossible unless protein and surrounding lipid are considered as a functional unit

Proposição de método de gestão para doenças crônicas: estudo de caso – Diabetes mellitus na Policlínica Naval Nossa Senhora da Glória

A partir de pesquisa bibliográfica e pesquisa em campo, uma metodologia foi construída para dar a organização estudada a competência de questionar e propor melhorias para seu fluxo de atividades. Foi feito desenvolvimento de um painel de indicadores de desempenho específicos para o Diabetes Mellitus, visualização agregada dos processos de negócios e proposições de melhoria a partir da análise dos processos.A partir do conhecimento adquirido durante entrevistas e atividades participativas com a gestão da organização estudada, o método foi extrapolado para um manual do processo de desenvolvimento deste mesmo projeto para outras condições de saúde

Acute alcohol tolerance is intrinsic to the BKCa protein, but is modulated by the lipid environment

Ethanol tolerance, in which exposure leads to reduced sensitivity, is an important component of alcohol abuse and addiction. The molecular mechanisms underlying this process remain poorly understood. The BKCa channel plays a central role in the behavioral response to ethanol in Caenorhabditis elegans (Davies, A. G., Pierce-Shimomura, J. T., Kim, H., VanHoven, M. K., Thiele, T. R., Bonci, A., Bargmann, C. I., and McIntire, S. L. (2003) Cell 115, 655-666) and Drosophila (Cowmeadow, R. B., Krishnan, H. R., and Atkinson, N. S. (2005) Alcohol. Clin. Exp. Res. 29, 1777-1786) . In neurons, ethanol tolerance in BKCa channels has two components: a reduced number of membrane channels and decreased potentiation of the remaining channels (Pietrzykowski, A. Z., Martin, G. E., Puig, S. I., Knott, T. K., Lemos, J. R., and Treistman, S. N. (2004) J. Neurosci. 24, 8322-8332) . Here, heterologous expression coupled with planar bilayer techniques examines two additional aspects of tolerance in human BKCa channels. 1) Is acute tolerance observed in a single channel protein complex within a lipid environment reduced to only two lipids? 2) Does lipid bilayer composition affect the appearance of acute tolerance? We found that tolerance was observable in BKCa channels in membrane patches pulled from HEK cells and when they are placed into reconstituted 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine/1-palmitoyl-2-o leoyl-sn-glycero-3-phosphatidylserine membranes. Furthermore, altering bilayer thickness by incorporating the channel into lipid mixtures of 1,2-dioleoyl-3-phosphatidylethanolamine with phosphatidylcholines of increasing chain length, or with sphingomyelin, strongly affected the sensitivity of the channel, as well as the time course of the acute response. Ethanol sensitivity changed from a strong potentiation in thin bilayers to inhibition in thick sphingomyelin/1,2-dioleoyl-3-phosphatidylethanolamine bilayers. Thus, tolerance can be an intrinsic property of the channel protein-lipid complex, and bilayer thickness plays an important role in shaping the pattern of response to ethanol. As a consequence of these findings the protein-lipid complex should be treated as a unit when studying ethanol action

The relationship between duration of initial alcohol exposure and persistence of molecular tolerance is markedly nonlinear

The neuronal calcium- and voltage-activated BK potassium channel is modulated by ethanol, and plays a role in behavioral tolerance in vertebrates and invertebrates. We examine the influence of temporal parameters of alcohol exposure on the characteristics of BK molecular tolerance in the ventral striatum, an important component of brain reward circuitry. BK channels in striatal neurons of C57BL/6J mice exhibited molecular tolerance whose duration was a function of exposure time. After 6 h exposure to 20 mm (0.09 mg%) ethanol, alcohol sensitivity was suppressed beyond 24 h after withdrawal, while after a 1 or 3 h exposure, sensitivity had significantly recovered after 4 h. This temporally controlled transition to persistent molecular tolerance parallels changes in BK channel isoform profile. After withdrawal from 6 h, but not 3 h alcohol exposure, mRNA levels of the alcohol-insensitive STREX (stress axis-regulated exon) splice variant were increased. Moreover, the biophysical properties of BK channels during withdrawal from 6 h exposure were altered, and match the properties of STREX channels exogenously expressed in HEK 293 cells. Our results suggest a temporally triggered shift in BK isoform identity. Once activated, the transition does not require the continued presence of alcohol. We next determined whether the results obtained using cultured striatal neurons could be observed in acutely dissociated striatal neurons, after alcohol administration in the living mouse. The results were in remarkable agreement with the striatal culture data, showing persistent molecular tolerance after injections producing 6 h of intoxication, but not after injections producing only 3 h of intoxication

Effects of Toxins on Ca 2+ Currents and Peptide Release from Nerve Terminals a

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72911/1/j.1749-6632.1994.tb26610.x.pd