704 research outputs found

    An integrated approach to teaching Aegean archaeology and archaeological science

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    Outlined here is a course that would serve as an introduction to archaeological science, specifically within the context of Aegean Prehistory. The main objective of this course is to expose students early in their archaeological careers to a variety of methods and questions, and to depart from the culture-historical perspective that typifies introductory survey courses. The class structure is equal parts lecture and discussion, moving between learning how the methods work and evaluating case studies. All graded assignments build on one another, guiding the students through designing their own research project. The ultimate goals of the assignments are to build key writing and professional skills, develop a basic understanding of research design, and to instill confidence that the student can contribute to the production of knowledge, whatever field he or she decides to pursue

    The Specificity and Regulation of Human Histone Deacetylase 8.

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    Post-translational modifications (PTMs) of proteins increase the complexity of the proteome, alter protein function, and play important roles in cellular function. Lysine acetylation, catalyzed by lysine acetyltransferases, is an important post-translational modification of proteins, including histones, transcription factors, and cytoplasmic proteins. The modification is reversible; hydrolysis is catalyzed by histone deacetylases (HDACs). Lysine deacetylation is important for regulating cellular processes, and aberrant deacetylation is implicated in diseases including cancer. HDAC8 is a metal-dependent HDAC that is activated by Zn(II) and Fe(II) under in vitro conditions, and altering the metal ion identity affects activity. This enzyme is a therapeutic target for cancers, parasitic infection, and a developmental disorder; however, therapeutic research is impeded by the lack of knowledge regarding HDAC substrate recognition and regulation and by the challenge of identifying HDAC substrates and binding partners. My research has focused on the substrate specificity, metal dependence, and regulation by phosphorylation of HDAC8. I have shown that the sequence specificity of HDAC8 toward peptide substrates is dependent on the identity of the catalytic metal ion. Additionally, I have investigated regulation of HDAC8 by phosphorylation on residue Ser39, using the S39E mutant as a mimetic, demonstrating that this modification significantly alters metal binding properties of HDAC8, decreases HDAC8-catalyzed deacetylation of peptides, and alters substrate binding. I have shown that HDAC8 exhibits changes in substrate specificity for singly acetylated octamers and nucleosome in vitro, compared to peptide substrates representing the same sites. Elucidating the mechanisms that regulate HDAC8 substrate specificity is important for determining the role of this enzyme in normal and pathophysiological processes in the cell.PHDChemical BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/116782/1/pitcairn_1.pd

    Evaluation of uptake mechanisms of phosphate by Fe(III)(oxyhydr)oxides in Early Proterozoic oceanic conditions

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    Banded iron formations (BIF) are proxies of global dissolved inorganic phosphate (DIP) content in Precambrian marine waters. Estimates of Precambrian DIP rely on constraining the mechanisms by which Fe(III)(oxyhydr)oxides scavenge DIP in NaCl solutions mimicking elevated Precambrian marine Si and Fe(II) concentrations. The two DIP binding modes suggested for Early Proterozoic marine waters are 1) surface attachment on pre-formed Fe(III)(oxyhydr)oxides (adsorption), and 2) incorporation of P into actively growing Fe(III)(oxyhydr)oxides (coprecipitation) during the oxidation of Fe(II) to Fe(III)(oxyhydr)oxides in the presence of DIP. It has been suggested that elevated Si concentrations such as those suggested for Precambrian seawater, strongly inhibit adsorption of DIP in Fe(III)(oxyhydr)oxides, however recent coprecipitation experiments show that DIP is scavenged by Fe(III)(oxyhydr)oxides in the presence of Si, seawater cations and hydrothermal As. In this study we show that the DIP uptake onto Fe(III)(oxyhydr)oxides by adsorption is less than 5% of that by coprecipitation. Differences in surface attachment and the possibility of structural capture within the Fe(III)(oxyhydr)oxides are inferred from the robust influence Si has on DIP binding during adsorption, but inhibited for coprecipitation when As(III) and As(V) are present. The data imply that in the Early Proterozoic open oceans, Fe(III)(oxyhydr)oxides precipitated when deep anoxic Fe(II)-rich waters rose and mixed with the first permanently oxygenated ocean surface waters, caused DIP removal from surface waters through coprecipitation rather than adsorption. Local variations in DIP and perhaps even stratification of DIP in the oceans were likely created from the continuous removal of DIP from surface waters by Fe(III)(oxyhydr)oxides, and its partial release into the anoxic bottom waters and in buried sediments. In addition to a DIP famine, the selectivity for DIP over As(V) may have led to As enrichment in surface waters both of which would have most likely decreased the productivity of cyanobacteria and O2 production

    Christian v R (No 2) [2006] PNCA 1 (2 March 2006)

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    Judgement of the Court of Appeals, as posted on the Pacific Islands Legal Institute (PacLII) website

    Effects of nicotine on attention: role of orexin-1 receptors

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    The orexin (also called hypocretin) system projects to a wide array of brain regions and is activated by drugs of abuse. The orexin system is best known for its function in wakefulness and arousal, but recent research has suggested that orexins play a vital role in attentional processing. The orexin-1 receptor has been implicated in crucial mechanisms of attention, specifically the transmission of acetylcholine to the cortex. Nicotine is a commonly administered psychoactive drug that has been shown to have cognitive-enhancing effects. Nicotine appears to target the orexin system, suggesting a potential role of the orexin system in mediating the cognitive enhancing effects seen with nicotine. However, the role of orexinergic function in the attentional-promoting effects of nicotine has not been fully described. The present study was designed with two goals in mind: 1) to identify a nicotine dose that improves rat performance in a sustained-attention task and 2) to examine the effect of chronic nicotine administration in conjunction with a selective orexin-1 antagonist, SB-334867, in rats in a sustained-attention task. The results of these experiments suggest that acute nicotine administration impairs attentional functioning, and that chronic nicotine administration slightly improves performance in the sustained-attentional task. Administration of chronic nicotine with SB-334867 blocks the beneficial effect of chronic nicotine in the sustained-attention task. Although these data are preliminary, the findings of this study could provide a novel target that mimics nicotine-induced cognitive activation and give insight into the behavioral and attentional effects of nicotinic activation and orexin-1 antagonism

    A Critical Analysis of the Uniformity of International Maritime Law and Multimodal Transport Containing a Sea Leg.

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    The need for uniformity in international maritime law has been long recognised. Each international treaty is drafted and ratified with the intention of drawing the legal rules governing the carriage of goods by sea closer together. This is not always the end result, however, with varying decisions and a plethora of interpretations creating a system of rules and judgements that are as dynamic as the area of law itself. From determining when a certain treaty will apply, to when a carrier will be able to rely on a specific defence, the outcome is not always clear and can change with a simple decision of which legal jurisdiction to issue proceedings in. The effect this has on the protection of carriers can be substantial; circumstances where a carrier may have been able to rely on a certain defence in one jurisdiction may not be sufficient in another. This article will analyse the current rules and determine whether carriers have sufficient protection, whether there is sufficient uniformity in the law governing carriage of goods by sea and what can be done to increase uniformity. The idea of whether an international court of tribunal being created in an attempt to unify and standardise interpretations of the Hague-Visby Rules will also be discussed. Multimodal transport is also an issue; with the presence of treaties governing the individual legs of the journey as well as treaties purporting to govern the whole carriage. As to which treaty is the correct one, uncertainty prevails

    Carbonate alteration of ophiolitic rocks in the Arabian–Nubian Shield of Egypt: sources and compositions of the carbonating fluid and implications for the formation of Au deposits

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    Ultramafic portions of ophiolitic fragments in the Arabian–Nubian Shield (ANS) show pervasive carbonate alteration forming various degrees of carbonated serpentinites and listvenitic rocks. Notwithstanding the extent of the alteration, little is known about the processes that caused it, the source of the CO2 or the conditions of alteration. This study investigates the mineralogy, stable (O, C) and radiogenic (Sr) isotope composition, and geochemistry of suites of variably carbonate altered ultramafics from the Meatiq area of the Central Eastern Desert (CED) of Egypt. The samples investigated include least-altered lizardite (Lz) serpentinites, antigorite (Atg) serpentinites and listvenitic rocks with associated carbonate and quartz veins. The C, O and Sr isotopes of the vein samples cluster between −8.1‰ and −6.8‰ for ÎŽ13C, +6.4‰ and +10.5‰ for ÎŽ18O, and 87Sr/86Sr of 0.7028–0.70344, and plot within the depleted mantle compositional field. The serpentinites isotopic compositions plot on a mixing trend between the depleted-mantle and sedimentary carbonate fields. The carbonate veins contain abundant carbonic (CO2±CH4±N2) and aqueous-carbonic (H2O-NaCl-CO2±CH4±N2) low salinity fluid, with trapping conditions of 270–300°C and 0.7–1.1 kbar. The serpentinites are enriched in Au, As, S and other fluid-mobile elements relative to primitive and depleted mantle. The extensively carbonated Atg-serpentinites contain significantly lower concentrations of these elements than the Lz-serpentinites suggesting that they were depleted during carbonate alteration. Fluid inclusion and stable isotope compositions of Au deposits in the CED are similar to those from the carbonate veins investigated in the study and we suggest that carbonation of ANS ophiolitic rocks due to influx of mantle-derived CO2-bearing fluids caused break down of Au-bearing minerals such as pentlandite, releasing Au and S to the hydrothermal fluids that later formed the Au-deposits. This is the first time that gold has been observed to be remobilized from rocks during the lizardite–antigorite transition

    The redesign of the global financial architecture :forums, institutions, and state power

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    PhD ThesisThis research examines the internationally coordinated, state-led response to the 2007- 2008 economic and financial crisis. It addresses the construction of ‘alternative narratives’ which encompass a partial revision of the economic paradigm, with a particular emphasis on the role of international financial regulatory authority, its rules and institutionalization. The meta-theoretical theme at the centre of this thesis involves the manner in which severe crisis episodes provoke and also reveal the underlying tension and contestation between ‘market authority’ and ‘state authority’ in relation to the regulation of the world economy, financial system and firms, with the goal of ensuring maximization of long-term systemic stability and crisis prevention. The construction of alternative crisis-driven narratives is in part a reaction to the previous ideological hegemonic domination of laissez faire neo-liberal beliefs as applied to deregulation (i.e., of self-regulation by markets and private sector actors in the financial sector). The thesis identifies and examines a paradigm shift in response to the crisis: a move from the dominance of market authority to the reassertion of state authority over financial markets and actors. It addresses the way in which crisis narratives are constructed in response to such episodes and the policy implications of paradigm shifts when they occur. The thesis empirically examines the elite state-level crisis response and its policy consequences, with particular emphasis on the institutional reforms most important to the construction, post-crisis, of a ‘new global financial architecture’. A principal argument within the thesis is that the severity of the financial crisis precipitated a rapid shift in the policy narrative held to by the central banking epistemic community, which constitutes a paradigm shift, and which led to a series of institutional and policy reforms addressing the application of state power and regulatory authority over global financial markets and firms
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