Metal-free restorations: esthetic considerations, treatment planning, preparation, manufacturing, luting, and followup

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Corticosterone Regulates Both Naturally Occurring and Cocaine‐Induced Dopamine Signaling by Selectively Decreasing Dopamine Uptake

Stressful and aversive events promote maladaptive reward‐seeking behaviors such as drug addiction by acting, in part, on the mesolimbic dopamine system. Using animal models, data from our laboratory and others show that stress and cocaine can interact to produce a synergistic effect on reward circuitry. This effect is also observed when the stress hormone corticosterone is administered directly into the nucleus accumbens (NAc), indicating that glucocorticoids act locally in dopamine terminal regions to enhance cocaine\u27s effects on dopamine signaling. However, prior studies in behaving animals have not provided mechanistic insight. Using fast‐scan cyclic voltammetry, we examined the effect of systemic corticosterone on spontaneous dopamine release events (transients) in the NAc core and shell in behaving rats. A physiologically relevant systemic injection of corticosterone (2 mg/kg i.p.) induced an increase in dopamine transient amplitude and duration (both voltammetric measures sensitive to decreases in dopamine clearance), but had no effect on the frequency of transient release events. This effect was compounded by cocaine (2.5 mg/kg i.p.). However, a second experiment indicated that the same injection of corticosterone had no detectable effect on the dopaminergic encoding of a palatable natural reward (saccharin). Taken together, these results suggest that corticosterone interferes with naturally occurring dopamine uptake locally, and this effect is a critical determinant of dopamine concentration specifically in situations in which the dopamine transporter is pharmacologically blocked by cocaine

Assessment of the State of the Art of Integrated Vehicle Health Management Technologies as Applicable to Damage Conditions

A survey of literature from academia, industry, and other Government agencies assessed the state of the art in current integrated vehicle health management (IVHM) aircraft technologies. These are the technologies that are used for assessing vehicle health at the system and subsystem level. This study reports on how these technologies are employed by major military and commercial platforms for detection, diagnosis, prognosis, and mitigation. Over 200 papers from five conferences from the time period of 2004 to 2009 were reviewed. Over 30 of these IVHM technologies are then mapped into the 17 different adverse event damage conditions identified in a previous study. This study illustrates existing gaps and opportunities for additional research by the NASA IVHM Project

Causal Factors and Adverse Events of Aviation Accidents and Incidents Related to Integrated Vehicle Health Management

Causal factors in aviation accidents and incidents related to system/component failure/malfunction (SCFM) were examined for Federal Aviation Regulation Parts 121 and 135 operations to establish future requirements for the NASA Aviation Safety Program s Integrated Vehicle Health Management (IVHM) Project. Data analyzed includes National Transportation Safety Board (NSTB) accident data (1988 to 2003), Federal Aviation Administration (FAA) incident data (1988 to 2003), and Aviation Safety Reporting System (ASRS) incident data (1993 to 2008). Failure modes and effects analyses were examined to identify possible modes of SCFM. A table of potential adverse conditions was developed to help evaluate IVHM research technologies. Tables present details of specific SCFM for the incidents and accidents. Of the 370 NTSB accidents affected by SCFM, 48 percent involved the engine or fuel system, and 31 percent involved landing gear or hydraulic failure and malfunctions. A total of 35 percent of all SCFM accidents were caused by improper maintenance. Of the 7732 FAA database incidents affected by SCFM, 33 percent involved landing gear or hydraulics, and 33 percent involved the engine and fuel system. The most frequent SCFM found in ASRS were turbine engine, pressurization system, hydraulic main system, flight management system/flight management computer, and engine. Because the IVHM Project does not address maintenance issues, and landing gear and hydraulic systems accidents are usually not fatal, the focus of research should be those SCFMs that occur in the engine/fuel and flight control/structures systems as well as power systems

Commercial Aircraft Integrated Vehicle Health Management Study

Statistical data and literature from academia, industry, and other government agencies were reviewed and analyzed to establish requirements for fixture work in detection, diagnosis, prognosis, and mitigation for IVHM related hardware and software. Around 15 to 20 percent of commercial aircraft accidents between 1988 and 2003 involved inalftfnctions or failures of some aircraft system or component. Engine and landing gear failures/malfunctions dominate both accidents and incidents. The IVI vl Project research technologies were found to map to the Joint Planning and Development Office's National Research and Development Plan (RDP) as well as the Safety Working Group's National Aviation Safety Strategic. Plan (NASSP). Future directions in Aviation Technology as related to IVHlvl were identified by reviewing papers from three conferences across a five year time span. A total of twenty-one trend groups in propulsion, aeronautics and aircraft categories were compiled. Current and ftiture directions of IVHM related technologies were gathered and classified according to eight categories: measurement and inspection, sensors, sensor management, detection, component and subsystem monitoring, diagnosis, prognosis, and mitigation

Corticosterone Potentiation of Cocaine-Induced Reinstatement of Conditioned Place Preference in Mice is Mediated by Blockade of the Organic Cation Transporter 3

The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using a dose that reproduced stress-level plasma concentrations) potentiated cocaine-primed reinstatement of extinguished cocaine-induced conditioned place preference. Corticosterone failed to re-establish extinguished preference alone but produced a leftward shift in the dose–response curve for cocaine-primed reinstatement. A similar potentiating effect was observed upon pretreatment of mice with the non-glucocorticoid OCT3 blocker, normetanephrine. To determine the role of OCT3 blockade in these effects, we examined the abilities of corticosterone and normetanephrine to potentiate cocaine-primed reinstatement in OCT3-deficient and wild-type mice. Conditioned place preference, extinction and reinstatement of extinguished preference in response to low-dose cocaine administration did not differ between genotypes. However, corticosterone and normetanephrine failed to potentiate cocaine-primed reinstatement in OCT3-deficient mice. Together, these data provide the first direct evidence that the interaction of corticosterone with OCT3 mediates corticosterone effects on drug-seeking behavior and establish OCT3 function as an important determinant of susceptibility to cocaine use

Thermal error modelling for real-time error compensation

A modelling strategy for the prediction of both the scalar and the position-dependent thermal error components is presented. Two types of empirical modelling method based on the multiple regression analysis (MRA) and the artificial neural network (ANN) have been proposed for the real-time prediction of thermal errors with multiple temperature measurements. Both approaches have a systematic and computerised algorithm to search automatically for the nonlinear and interaction terms between different temperature variables. The experimental results on a machining centre show that both the MRA and the ANN can accurately predict the time-variant thermal error components under different spindle speeds and temperature fields. The accuracy of a horizontal machining centre can be improved through experiment by a factor of ten and the errors of a cut aluminium workpiece owing to thermal distortion have been reduced from 92.4 µm to 7.2 µm in the lateral direction. The depth difference due to the spindle thermal growth has been reduced from 196 µm to 8 µm.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45884/1/170_2005_Article_BF01239613.pd

Unique and conserved MicroRNAs in wheat chromosome 5D revealed by next-generation sequencing

MicroRNAs are a class of short, non-coding, single-stranded RNAs that act as post-transcriptional regulators in gene expression. miRNA analysis of Triticum aestivum chromosome 5D was performed on 454 GS FLX Titanium sequences of flow sorted chromosome 5D with a total of 3,208,630 good quality reads representing 1.34x and 1.61x coverage of the short (5DS) and long (5DL) arms of the chromosome respectively. In silico and structural analyses revealed a total of 55 miRNAs; 48 and 42 miRNAs were found to be present on 5DL and 5DS respectively, of which 35 were common to both chromosome arms, while 13 miRNAs were specific to 5DL and 7 miRNAs were specific to 5DS. In total, 14 of the predicted miRNAs were identified in wheat for the first time. Representation (the copy number of each miRNA) was also found to be higher in 5DL (1,949) compared to 5DS (1,191). Targets were predicted for each miRNA, while expression analysis gave evidence of expression for 6 out of 55 miRNAs. Occurrences of the same miRNAs were also found in Brachypodium distachyon and Oryza sativa genome sequences to identify syntenic miRNA coding sequences. Based on this analysis, two other miRNAs: miR1133 and miR167 were detected in B. distachyon syntenic region of wheat 5DS. Five of the predicted miRNA coding regions (miR6220, miR5070, miR169, miR5085, miR2118) were experimentally verified to be located to the 5D chromosome and three of them : miR2118, miR169 and miR5085, were shown to be 5D specific. Furthermore miR2118 was shown to be expressed in Chinese Spring adult leaves. miRNA genes identified in this study will expand our understanding of gene regulation in bread wheat

Antiangiogenic Activity of 2-Deoxy-D-Glucose

During tumor angiogenesis, endothelial cells (ECs) are engaged in a number of energy consuming biological processes, such as proliferation, migration, and capillary formation. Since glucose uptake and metabolism are increased to meet this energy need, the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on in vitro and in vivo angiogenesis were investigated.In cell culture, 2-DG inhibited EC growth, induced cytotoxicity, blocked migration, and inhibited actively forming but not established endothelial capillaries. Surprisingly, 2-DG was a better inhibitor of these EC properties than two more efficacious glycolytic inhibitors, 2-fluorodeoxy-D-glucose and oxamate. As an alternative to a glycolytic inhibitory mechanism, we considered 2-DG's ability to interfere with endothelial N-linked glycosylation. 2-DG's effects were reversed by mannose, an N-linked glycosylation precursor, and at relevant concentrations 2-DG also inhibited synthesis of the lipid linked oligosaccharide (LLO) N-glycosylation donor in a mannose-reversible manner. Inhibition of LLO synthesis activated the unfolded protein response (UPR), which resulted in induction of GADD153/CHOP and EC apoptosis (TUNEL assay). Thus, 2-DG's effects on ECs appeared primarily due to inhibition of LLOs synthesis, not glycolysis. 2-DG was then evaluated in two mouse models, inhibiting angiogenesis in both the matrigel plug assay and the LH(BETA)T(AG) transgenic retinoblastoma model.In conclusion, 2-DG inhibits endothelial cell angiogenesis in vitro and in vivo, at concentrations below those affecting tumor cells directly, most likely by interfering with N-linked glycosylation rather than glycolysis. Our data underscore the importance of glucose metabolism on neovascularization, and demonstrate a novel approach for anti-angiogenic strategies