Post-training ethanol disrupts trace conditioned fear in rats: Effects of timing of ethanol, dose and trace interval duration

Ethanol has complex effects on memory performance, although hippocampus-dependent memory may be especially vulnerable to disruption by acute ethanol intoxication occurring during or shortly after a training episode. In the present experiments, the effects of post-training ethanol on delay and trace fear conditioning were examined in adolescent rats. In Experiment 1, 30-day-old Sprague-Dawley rats were given delay or trace conditioning trials in which a 10 s flashing light CS was paired with a 0.5 mA shock US. For trace groups, the trace interval was 10 s. On days 31-33, animals were administered ethanol once daily (0.0 or 2.5 g/kg via intragastric intubation), and on day 34 animals were tested for CS-elicited freezing. Results showed that post-training ethanol affected the expression of trace, but had no effect on delay conditioned fear. Experiment 2 revealed that this effect was dose-dependent; doses lower than 2.5 g/kg were without effect. Experiment 3 evaluated whether proximity of ethanol to the time of training or testing was critical. Results show that ethanol administration beginning 24 h after training was more detrimental to trace conditioned freezing than administration that was delayed by 48 h. Finally, in Experiment 4 animals were trained with one of three different trace intervals: 1, 3 or 10 s. Results indicate that post-training administration of 2.5 g/kg ethanol disrupted trace conditioned fear in subjects trained with a 10 s, but not with a I or 3 s, trace interval. Collectively the results suggest that ethanol administration impairs post-acquisition memory processing of hippocampus-dependent trace fear conditioning. (C) 2008 Elsevier Inc. All rights reserved

A Novel Peptide Enhances Therapeutic Efficacy of Liposomal Anti-Cancer Drugs in Mice Models of Human Lung Cancer

Lung cancer is the leading cause of cancer-related mortality worldwide. The lack of tumor specificity remains a major drawback for effective chemotherapies and results in dose-limiting toxicities. However, a ligand-mediated drug delivery system should be able to render chemotherapy more specific to tumor cells and less toxic to normal tissues. In this study, we isolated a novel peptide ligand from a phage-displayed peptide library that bound to non-small cell lung cancer (NSCLC) cell lines. The targeting phage bound to several NSCLC cell lines but not to normal cells. Both the targeting phage and the synthetic peptide recognized the surgical specimens of NSCLC with a positive rate of 75% (27 of 36 specimens). In severe combined immunodeficiency (SCID) mice bearing NSCLC xenografts, the targeting phage specifically bound to tumor masses. The tumor homing ability of the targeting phage was inhibited by the cognate synthetic peptide, but not by a control or a WTY-mutated peptide. When the targeting peptide was coupled to liposomes carrying doxorubicin or vinorelbine, the therapeutic index of the chemotherapeutic agents and the survival rates of mice with human lung cancer xenografts markedly increased. Furthermore, the targeting liposomes increased drug accumulation in tumor tissues by 5.7-fold compared with free drugs and enhanced cancer cell apoptosis resulting from a higher concentration of bioavailable doxorubicin. The current study suggests that this tumor-specific peptide may be used to create chemotherapies specifically targeting tumor cells in the treatment of NSCLC and to design targeted gene transfer vectors or it may be used one in the diagnosis of this malignancy

Today’s Runaway Slaves: Unauthorized Immigrants in a Federalist Framework

"Today’s Runaway Slaves" engages in long-standing debates about American federalism, slavery and immigration law, civil and immigrant rights, and racial politics. The central puzzle it addresses is how American federalism and social movements shape the development of state and local sanctuary laws that protect classes of people, who federal law considers unlawfully present inside the United States. I employ an innovative research design of documenting and comparing laws protecting runaway slaves from 1780-1860 with contemporary laws on Central American asylum seekers from 1980-1997 and undocumented immigrants from 2000-2017. From this original research, I offer analysis of what I term a "federalism conflict" between federal and state/local laws on free movement and presence, and develop the term "free presence" to make sense of how sanctuary laws accumulate to decouple states from enforcing federal law in ways that benefit the life chances of runaway slaves and undocumented immigrants.The dissertation makes two contributions: a long-run institutional account of sanctuary policies rooted in the U.S. Constitution and federalism; a general theory accounting for the proliferation of sanctuary policies and variation in each historical period. On the long-run question, I argue that the courts institutionalize states’ semi-sovereignty and what I term a federalism conflict that has always allowed for sanctuary laws to emerge and proliferate, which I reveal through court decisions on slavery, alienage, and immigration. On the empirical question, I advance a theory of coalition building in a federalism framework to explain variation in sanctuary policies in antebellum and contemporary periods. Sanctuary policies emerge out similar fights for federal abolition and federal immigration reform. I posit that federalism’s structure shapes the timing of where and when sanctuary policies emerge: national activists commit to a federal reform strategy, and sanctuary policies gain clout only after numerous failures at the national level occur. National activists respond to repeated national failure by revising their reform strategy to include subfederal sanctuary polices; after this shift, my theory posits that state and local coalition building contexts explain the differences in the timing and scope of sanctuary policies across jurisdictions.Sanctuary policies animate long-standing debates in American politics. Without comprehensive reform at the national level, states and localities play a critical protective role over runaway slaves and undocumented immigrants, who live in fear of re-enslavement and deportation. My dissertation explains how federalism empowers advocacy coalitions within states and localities to contest national policy, connects America’s abolitionist heritage to salient questions shaping today’s immigration debates, develops a timely framework and concepts to understand why classes of people lacking federal legal status are welcomed by states and localities, and why sanctuary policies contribute to the ongoing project of American democracy and civil rights

Today’s Runaway Slaves: Unauthorized Immigrants in a Federalist Framework

"Today’s Runaway Slaves" engages in long-standing debates about American federalism, slavery and immigration law, civil and immigrant rights, and racial politics. The central puzzle it addresses is how American federalism and social movements shape the development of state and local sanctuary laws that protect classes of people, who federal law considers unlawfully present inside the United States. I employ an innovative research design of documenting and comparing laws protecting runaway slaves from 1780-1860 with contemporary laws on Central American asylum seekers from 1980-1997 and undocumented immigrants from 2000-2017. From this original research, I offer analysis of what I term a "federalism conflict" between federal and state/local laws on free movement and presence, and develop the term "free presence" to make sense of how sanctuary laws accumulate to decouple states from enforcing federal law in ways that benefit the life chances of runaway slaves and undocumented immigrants.The dissertation makes two contributions: a long-run institutional account of sanctuary policies rooted in the U.S. Constitution and federalism; a general theory accounting for the proliferation of sanctuary policies and variation in each historical period. On the long-run question, I argue that the courts institutionalize states’ semi-sovereignty and what I term a federalism conflict that has always allowed for sanctuary laws to emerge and proliferate, which I reveal through court decisions on slavery, alienage, and immigration. On the empirical question, I advance a theory of coalition building in a federalism framework to explain variation in sanctuary policies in antebellum and contemporary periods. Sanctuary policies emerge out similar fights for federal abolition and federal immigration reform. I posit that federalism’s structure shapes the timing of where and when sanctuary policies emerge: national activists commit to a federal reform strategy, and sanctuary policies gain clout only after numerous failures at the national level occur. National activists respond to repeated national failure by revising their reform strategy to include subfederal sanctuary polices; after this shift, my theory posits that state and local coalition building contexts explain the differences in the timing and scope of sanctuary policies across jurisdictions.Sanctuary policies animate long-standing debates in American politics. Without comprehensive reform at the national level, states and localities play a critical protective role over runaway slaves and undocumented immigrants, who live in fear of re-enslavement and deportation. My dissertation explains how federalism empowers advocacy coalitions within states and localities to contest national policy, connects America’s abolitionist heritage to salient questions shaping today’s immigration debates, develops a timely framework and concepts to understand why classes of people lacking federal legal status are welcomed by states and localities, and why sanctuary policies contribute to the ongoing project of American democracy and civil rights

A multichannel, synchronous laser signal processing system

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