The noncompetitive NMDA receptor antagonist ketamine produces rapid and sustained antidepressant effects in patients suffering from major depressive disorder. However, abuse liability is a concern. To further evaluate the relationship between antidepressant-like and abuse-related effects of NMDA receptor antagonists, this study evaluated the effects of ketamine, MK-801, and phencyclidine in male Sprague-Dawley rats responding under two procedures that have been used to assess antidepressant-like effects [differential-reinforcement-of-low-rate (DRL) 72 s schedule of food reinforcement] and abuse-related drug effects [intracranial self-stimulation (ICSS)]. Under DRL 72 s, ketamine produced an antidepressant-like effect by increasing reinforcers, decreasing responses, and producing a rightward shift in the peak location of the interresponse time (IRT) distributions. Phencyclidine produced a modest antidepressant-like effect by increasing reinforcers and decreasing responses, but did not shift the IRT distributions. In contrast, MK-801 produced a psychostimulant-like effect by decreasing reinforcers, increasing responses, and producing a leftward shift in the peak location of the IRT distributions. The antidepressant-like effects of ketamine on the DRL 72 s procedure do not appear to be mediated by inhibiting the reuptake of serotonin via serotonin transporters or antagonism of 5-HT2 receptors. Additionally, the dissociable effects of ketamine and MK-801 in the DRL 72 s procedure may be mediated by 5-HT2 receptors. Following acute administration, ketamine produced only dose- and time-dependent depression of ICSS and failed to produce an abuse-related facilitation of ICSS at any dose or pretreatment time. Repeated dosing with ketamine produced dose-dependent tolerance to the rate-decreasing effects of ketamine but failed to unmask expression of ICSS facilitation. Termination of ketamine treatment failed to produce withdrawal-associated decreases in ICSS. In contrast, MK-801 and phencyclidine effects produced dose- and time-dependent facilitation of ICSS by MK-801. Taken together, our findings provide further evidence that expression of these antidepressant-like and abuse-related effects of ketamine, phencyclidine, and MK-801 may be related to NMDA receptor affinity.

In the waning days of apartheid, an operative of Umkhonto we Sizwe, the armed wing of South Africa’s most powerful dissident organization the African National Congress, returned to his home community of N’wamitwa after over a decade in exile. His mission was to spark a people’s war, an imported form of revolutionary warfare developed by Mao Zedong and perfected by the North Vietnamese in their revolutionary struggles. In this thesis I examine the political context in which the ANC chose to adopt the strategy and how it was imported into South Africa. The later chapters of this thesis use N’wamitwa as a case study examining how a people’s war is successfully implemented on the ground. I argue that one can see the three phases of a people’s war as articulated by Mao play out in N’wamitwa between the years 1989 to 1994 This piece was largely written and researched using oral testimony from nine former members of the MK in N’wamitwa and thus can also be seen as a collection of personal histories of the South African Freedom Struggle. / Graduate

Student Number : 0216658A - PhD thesis - School of Social Sciences - Faculty of Humanities / This thesis is a study of underground organisation from the 1950s until 1976, though it also draws on material prior to and after these periods. It delves into an area of social activity that has been relatively invisible in scholarship on South Africa and resistance history. The study considers the concept of underground operations. It is taken to include not only the place where the ‘final’ activities may have taken place, but those countries where cadres were trained or housed, even if this would normally be characterised as located in ‘exile’. It is ‘outside’, but it such activities are also treated as part of the underground phenomenon considered as a whole. At the level of historiography the thesis is a re-reading of early ANC underground, partly giving a different interpretation to existing literature, but also relying on the insights of oral informants. The establishment of the SACP underground is fleshed out through interview material, but the thesis challenges the notion that the Party controlled the ANC, arguing in contrast that the conditions of the alliance demanded limitations on SACP’s autonomy. In the period after Rivonia the conventional historiography speaks of a lull and an absence of the ANC and its allies. The thesis provides evidence to contradict this showing that while there may have been silence, there was never absence. It also probes the relationship between ANC and Black Consciousness, where it shows far more overlap than much of the existing literature has disclosed. The study is at once a historical narrative and also an attempt to characterise the social character of this area of study, the special features that go to make up clandestine organisaton. Within this characterisation of underground activity, the thesis also probes the gendered nature of these activities, the definite impact of concepts of masculinity and femininity within a conventionally male terrain. Related to these questions the thesis probes the relationship between the personal and organisational, both at the level of individual decision-making and notions of love and realising emotions. The chapter on gender examines the denial of manhood to African men and considers ANC masculinities and assertion of the need to regain manhood in that context. The thesis also examines the entry of women into the male world of the army and underground, explaining many of the difficulties and the countervailing efforts of women as well as certain men to assert the rights of women to equal participation. The chapter on the impact of revolutionary activity on the personal examines the subordination of individual judgement to the collective and in the personal sphere, notions of revolutionary love, found not only in South Africa but in most revolutionary struggles, where ‘love for the people’ tends to displace inter-personal love. The final chapter –by way of an epilogue- examines the outcomes of struggles after 1976, initiated by various forces including the underground organisation. In this period ANC hegemony begins to consolidate and the character of that hegemony is broken down into various components.

Submitted by PPG Biologia Celular e Molecular (bcm@pucrs.br) on 2018-04-24T12:44:41Z No. of bitstreams: 1 KARINA_VIDARTE_GASPARY_DIS.pdf: 1111674 bytes, checksum: e2b2dc4b1b1eea8b10007b7c07f592ec (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-05-11T17:57:10Z (GMT) No. of bitstreams: 1 KARINA_VIDARTE_GASPARY_DIS.pdf: 1111674 bytes, checksum: e2b2dc4b1b1eea8b10007b7c07f592ec (MD5) / Made available in DSpace on 2018-05-11T18:03:07Z (GMT). No. of bitstreams: 1 KARINA_VIDARTE_GASPARY_DIS.pdf: 1111674 bytes, checksum: e2b2dc4b1b1eea8b10007b7c07f592ec (MD5) Previous issue date: 2018-02-08 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Memory and learning allow animals to adapt and modify their behavior towards new experiences. Some factors may result in memory deficits such as: neurodegenerative diseases, changes due to intoxication and the use of drugs. Zebrafish can be used to model complex human behavioral traits such as learning and memory. This study aims to establish a protocol for evaluating the object recognition memory or object location tasks in zebrafish. We evaluated novel object recognition memory and analyzed the exploration time of novel and familiar objects in the training and test sessions. There was a preference of the animal to explore the new object in comparison to the familiar object (61% of exploration time). We also evaluated the object location task and measured the exploration time of each object in the familiar and novel object locations. There was a preference of the animal to explore the object in the novel location in comparison to the object in the familiar location (63% of exploration time). We also evaluated the effect of the non-competitive NMDA receptor antagonist MK-801 on the object recognition and object location memory in zebrafish. In this regimen treatment, control (water only) and treated animals (5 ?M MK-801) presented a significant preference in exploring the familiar object in comparison to the new object (66 and 68% of exploration time, respectively); however, 10 ?M MK-801-treated animals did not show differences in the exploration time of the objects. In the object location task, the animals treated with the 5 or 10 ?M MK-801 did not show a significant preference for the familiar or novel location whereas the control group had a higher preference in exploring the object in the familiar location (64% of exploration time). Therefore, it is possible to suggest that 5 ?M MK-801 impaired the memory formation in an object location task, which is in agreement with previous studies demonstrating the cognitive deficit induced by MK-801 treatment in aversive and spatial memory. Considering the different responses of the control group between original task and in the regimen treatment, we evaluated the impact of habituation on cortisol levels of animals in three different protocols: 1) habituated at the experiment apparatus for 3 days (Condition 1 ? C1), 2) habituated at the experiment apparatus for 3 days plus treatment tank exposure at fourth day (Condition 2 - C2), 3) habituated at the treatment tank exposure and experiment apparatus for 3 days and exposed to treatment tank again at fourth day (Condition 3 ? C3). The results showed higher levels of cortisol in animals submitted to C2 and C3 conditions compared to animals submitted to C1. These results demonstrated that the animals submitted to treatment tank exposure have a different performance in object recognition and object location memory due to stress responses. Therefore, these tasks are prone to evaluate memory in physiological and pathological conditions, but its use is limited to perform pharmacological studies due to sensitivity to stress caused by manipulation. / A mem?ria permite que os animais possam adaptar e modificar seu comportamento diante de novas experi?ncias. Uma s?rie de fatores pode resultar num d?ficit de mem?ria como: doen?as neurodegenerativas, altera??es decorrentes de intoxica??es e uso de f?rmacos. O peixe-zebra vem sendo usado para modelar caracter?sticas comportamentais humanas complexas, como o aprendizado e mem?ria. Este estudo tem como objetivo estabelecer um protocolo para avaliar tarefas de mem?ria de reconhecimento de objetos ou de localiza??o de objetos no peixe-zebra. N?s avaliamos a mem?ria de reconhecimento de objeto novo e analisamos o tempo de explora??o de objetos novos e familiares nas sess?es de treino e teste. Houve uma prefer?ncia do animal em explorar o novo objeto em compara??o com o objeto familiar (61% do tempo de explora??o). Tamb?m avaliamos a tarefa de localiza??o de objeto e medimos o tempo de explora??o de cada objeto nos locais familiares e novos. Houve uma prefer?ncia do animal para explorar o objeto na localiza??o nova em compara??o com o objeto na localiza??o familiar (63% do tempo de explora??o). Tamb?m avaliamos o efeito do antagonista n?o competitivo do receptor NMDA MK-801 na mem?ria de reconhecimento de objeto novo e na localiza??o de objeto em peixe-zebra. Neste tratamento, o controle (somente ?gua) e os animais tratados (MK-801 5 ?M) apresentaram uma prefer?ncia significativa na explora??o do objeto familiar em compara??o com o novo objeto (66 e 68% do tempo de explora??o, respectivamente); no entanto, animais tratados com MK-801 10 ?M n?o mostraram diferen?as no tempo de explora??o dos objetos. Na tarefa de localiza??o de objeto, os animais tratados com MK-801 5 ou 10 ?M n?o mostraram prefer?ncia significativa pelo objeto na localiza??o familiar ou nova, enquanto que o grupo controle teve uma prefer?ncia maior em explorar o objeto na localiza??o familiar (64% de tempo de explora??o). Portanto, sugere-se que o MK-801 5 ?M prejudicou a forma??o da mem?ria em uma tarefa de localiza??o de objeto, o que est? de acordo com estudos pr?vios, demonstrando o d?ficit cognitivo induzido pelo MK-801 em mem?rias aversivas ou espaciais. Considerando as diferentes respostas do grupo controle entre a tarefa original e no tratamento, avaliamos o impacto da habitua??o nos n?veis de cortisol dos animais em tr?s protocolos diferentes: 1) habituado ao aparato experimental por 3 dias (Condi??o 1 - C1) 2) habituado ao aparato experimental por 3 dias mais a exposi??o ao aqu?rio de tratamento no quarto dia (Condi??o 2 - C2), 3) habituado na exposi??o ao aqu?rio de tratamento e no aparato experimental por 3 dias e exposto ao aqu?rio de tratamento novamente no quarto dia (Condi??o 3 - C3). Os resultados mostraram n?veis mais elevados de cortisol em animais submetidos a condi??es C2 e C3 em compara??o com animais submetidos a C1. Esses resultados demonstraram que os animais submetidos ? exposi??o ao aqu?rio de tratamento apresentam desempenho diferente nas tarefas de mem?ria de reconhecimento de objetos e de localiza??o do objeto devido ao estresse. Portanto, essas tarefas s?o adequadas para avaliar a mem?ria em condi??es fisiol?gicas e patol?gicas, mas seu uso ? limitado em estudos farmacol?gicos devido ? sensibilidade ao estresse causado pela manipula??o.

The Naval Postgraduate School is currently developing their first CubeSat, the Solar Cell Array Tester CubeSat, or NPS-SCAT. Launching a CubeSat, such as NPS-SCAT, requires environmental testing to ensure not only the success of the mission, but also the safety of other CubeSats housed in the same deployer. This thesis will address the development of CubeSat vibration testing methodology at NPS, including subsystem testing, engineering unit qualification, and flight unit testing. In addition, the new Cal Poly CubeSat Test POD Mk III will be introduced and evaluated based upon comparison with the Poly Picosatellite Orbital Deployer (P-POD). Using examples from the development of NPS-SCAT and test data from Cal Poly’s Test POD Mk III and P-POD, the current CubeSat testing methodology will be verified and an improved method for NPS CubeSat subsystem testing will be presented.

Previous research has shown that cannabidiol (CBD), a non-psychoactive compound in the hemp plant Cannabis sativa, may be useful in treating drug craving, one of the hallmarks of drug addiction. However, the neural mechanism by which CBD attenuates craving is poorly understood. Studies from other laboratories have shown that neuroplastic changes associated with brain NMDA glutamate systems may at least partially serve as a neural mechanism for craving. In the current study, the noncompetitive NMDA receptor antagonist MK-801 maleate was used to induce locomotor sensitization, a form of NMDA glutamate-mediated neuroplasticity, in mice to test the sensitization-attenuating potential of CBD. Separate groups of mice (N=8) received either CBD (1.0 mg/kg, i.p.) or saline thirty minutes prior to an intraperitoneal injection of MK-801 (0.5 mg/kg, i.p.) or saline and tested for locomotor performance in an open field (Induction Trial). Seventy-two hours later all mice, regardless of drug pretreatment, were tested for locomotor activity following a second administration (0.5 mg/kg, i.p.) of MK-801 (Sensitization Trial). Results revealed a significant difference across groups for the Induction Trial, with groups receiving SAL-MK801 and CBD-MK801 significantly more active than SAL-SAL and CBD-SAL groups. Pretreatment with CBD had no effect on the locomotor activating effects of MK-801 during the Sensitization Trial with similar levels of locomotor performance across drug groups. Possibilities for the lack of CBD effects are discussed, as well as implications and future research directions.

This paper tests for the Euro zone the hypothesis put forward by Sapir and Sekkat (1999) that synchronizing elections might improve welfare. After identifying a political budget cycle in the Euro zone we build a politico-macroeconomic model and simulate the effects of adopting a common election day in the 12 Euro zone member states. The results support most of the theoretical predictions by Sapir-Sekkat: (i) Synchronizing the elections could enhance GDP growth, reduce unemployment, but leads to increased inflation and in some countries to a deterioration of the budget; higher inflation forces ECB to monetary restrictions. (ii) If the synchronization happens asymmetrically - either only in the large or only in the small Euro zone countries - the result depends on the size of the spillovers. (iii) As anticipated in Sapir -Sekkat a common election day is a further step towards the desired "European business cycle", however, at the cost of increasing its amplitude. Harmonizing elections is another method of policy coordination. Whether this leads to higher welfare is a matter of weighting the different macroeconomic outcomes and it also depends on the model applied. (author's abstract) / Series: EI Working Papers / Europainstitut

A new paradigm has evolved in which multiple regulatory interactions between the skeletal and hematopoietic systems have been identified. Previous studies have demonstrated that megakaryocytes (MK) play a dual role in skeletal homeostasis by stimulating osteoblast proliferation and simultaneously inhibiting osteoclast (OC) development. Here we identify a novel regulatory pathway in which the main MK growth factor, thrombopoietin (TPO), directly regulates osteoclastogenesis. To study the role of TPO in OC development, spleen or bone marrow (BM) cells (2x10[exponent]6 cells/ml) or BM macrophages (BMM, 1x10[exponent]5 cells/ml) from C57BL/6 mice , as a source of OC precursors, were cultured with M-CSF (30 ng/ml) and RANKL (50 ng/ml) to induce OC formation. TPO (0.1-1000 ng/ml) and/or primary MK (0-0.5%), derived from C57BL/6 fetal livers, were titrated into these cultures and OC were identified as tartrate resistant acid phosphatase positive (TRAP+) giant cells with >3 nuclei. There was a significant, up to 15-fold reduction in OC formed when MK were added to all OC generating cultures, p < 0.001. Moreover, if OC generating cultures did not contain MK or MK progenitors, TPO treatment significantly enhanced OC formation up to six-fold, p < 0.01. This data demonstrates that MK are responsible for the inhibition of OC formation and that in cultures containing MK or MK progenitors such as BM or spleen cells, that TPO acts indirectly to inhibit OC formation by stimulating megakaryopoiesis, whereas in the absence of MK or MK progenitors TPO directly enhances OC formation. This conclusion is further supported by Real-Time PCR data which demonstrates that OC progenitors express c-mpl, the TPO receptor, albeit at low levels when compared to expression of c-mpl on MK. Finally, we have begun to dissect the c-mpl signaling pathway in OC progenitors. We have found that TPO induces tyrosine phosphorylation of several specific cellular proteins in the JAK/STAT pathway. Thus, TPO acts in a somewhat paradoxical manner by inhibiting OC formation through the stimulation of MK, while simultaneously playing a direct role in enhancing osteoclastogenesis.

(no abstract available)

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