Geoengineering to Avoid Overshoot: An Uncertainty Analysis

NASA Astrophysics Data System (ADS)

Tanaka, K.

2009-04-01

Geoengineering (or climate engineering) using stratospheric sulfur injections (Crutzen, 2006) has been called for research in case of an urgent need for stopping global warming when other mitigation efforts were exhausted. Although there are a number of concerns over this idea (e.g. Robock, 2008), it is still useful to consider geoengineering as a possible method to limit warming caused by overshoot. Overshoot is a feature accompanied by low stabilizations scenarios aiming for a stringent target (Rao et al., 2008) in which total radiative forcing temporarily exceeds the target before reaching there. Scenarios achieving a 50% emission reduction by 2050 produces overshoot. Overshoot could cause sustained warming for decades due to the inertia of the climate system. If stratospheric sulfur injections were to be used as a "last resort" to avoid overshoot, what would be the suitable start-year and injection profile of such an intervention? Wigley (2006) examined climate response to combined mitigation/geoengineering scenarios with the intent to avert overshoot. Wigley's analysis demonstrated a basic potential of such a combined mitigation/geoengineering approach to avoid temperature overshoot - however it considered only simplistic sulfur injection profiles (all started in 2010), just one mitigation scenario, and did not examine the sensitivity of the climate response to any underlying uncertainties. This study builds upon Wigley's premise of the combined mitigation/geoengineering approach and brings associated uncertainty into the analysis. First, this study addresses the question as to how much geoengineering intervention would be needed to avoid overshoot by considering associated uncertainty? Then, would a geoengineering intervention of such a magnitude including uncertainty be permissible in considering all the other side effects? This study begins from the supposition that geoengineering could be employed to cap warming at 2.0°C since preindustrial. A few mitigation scenarios having overshoot are formulated. Optimal injection profiles (start-year and magnitude) for capping temperature rise at 2.0°C are calculated for each mitigation scenario. The sensitivity of such results to the uncertain parameters (climate sensitivity, tropospheric aerosol forcing, and ocean diffusivity) is then examined - in particular, I account for the inter-dependency of the estimates of these parameters such that they are consistent with historical observations (e.g. temperature records) by using an inverse estimation approach. I use the simple climate model ACC2 (Tanaka and Kriegler et al., 2007; Tanaka, 2008) - which (unlike Wigley's MAGICC model (Wigley and Raper, 2001)) includes an inversion setup that allows for the exploration of parameter inter-dependency based on historical observational constraints. References Crutzen, P. J. (2006) Albedo enhancement by stratospheric sulfur injections: a contribution to resolve a policy dilemma? Climatic Change, 77, 211-219. Rao, S., K. Riahi, E. Stehfest, D. van Vuuren, C. Cho, M. den Elzen, M. Isaac, J. van Vliet (2008) IMAGE and MESSAGE scenarios limiting GHG concentration to low levels. Interim Report at International Institute for Applied Systems Analysis (IIASA) IR-08-020. 57 pp. http://www.iiasa.ac.at/Admin/PUB/Documents/IR-08-020.pdf Robock, A. (2008) 20 reasons why geoengineering may be a bad idea. Bulletin of the Atomic Scientists, 64, 14-18. Tanaka, K., E. Kriegler, T. Bruckner, G. Hooss, W. Knorr, T. Raddatz (2007) Aggregated Carbon Cycle, Atmospheric Chemistry, and Climate Model (ACC2): description of the forward and inverse modes. Reports on Earth System Science No. 40. Max Planck Institute for Meteorology, Hamburg, Germany. 188 pp. http://www.mpimet.mpg.de/wissenschaft/publikationen/erdsystemforschung.html Tanaka, K. (2008) Inverse estimation for the simple Earth system model ACC2 and its applications. Ph.D. dissertation. Hamburg, Germany: Hamburg Universität, International Max Planck Research School on Earth System Modelling, 296 pp. http://www.sub.uni-hamburg.de/opus/volltexte/2008/3654/ Wigley, T. M. L., S. C. B. Raper (2001) Interpretation of high projections for global-mean warming. Science, 293, 451-454. Wigley, T. M. L. (2006) A combined mitigation/geoengineering approach to climate stabilization. Science, 314, 452-454.

Geoengineering to Avoid Overshoot: An Analysis of Uncertainty

NASA Astrophysics Data System (ADS)

Tanaka, Katsumasa; Cho, Cheolhung; Krey, Volker; Patt, Anthony; Rafaj, Peter; Rao-Skirbekk, Shilpa; Wagner, Fabian

2010-05-01

Even if a drastic 50% CO2-equivalent emissions reduction is achieved by year 2050, the chances of exceeding a 2°C warming are still substantial due to the uncertainty in the climate system (Meinshausen et al., 2009). Moreover, a strong mitigation is accompanied by overshoot, in which the global-mean temperature temporarily exceeds the target before arriving there. We are motivated by the question as to how much geoengineering would be considered if it were to be used to avoid overshoot even combined with a strong mitigation? How serious would the side effects be expected? This study focuses on stratospheric sulfur injections among other geoengineering proposals, the idea of which has been put forward by Crutzen (2006) and reviewed by Rasch et al. (2008). There are a number of concerns over geoengineering (e.g. Robock, 2008). But the concept of geoengineering requires further research (AMS, 2009). Studying geoengineering may be instructive to revisit the importance of mainstream mitigation strategies. The motivations above led to the following two closely linked studies: 1) Mitigation and Geoengineering The first study investigates the magnitude and start year of geoengineering intervention with the intent to avoid overshoot. This study explores the sensitivity of geoengineering profile to associated uncertainties in the climate system (climate sensitivity, tropospheric aerosol forcing, and ocean diffusivity) and in mitigation scenarios (target uncertainty (450ppm CO2-eq and 400ppm CO2-eq) and baseline uncertainty (A2, B1, and B2)). This study builds on Wigley's premise that demonstrated a basic potential of such a combined mitigation/geoengineering approach (Wigley, 2006) - however it did not examine the sensitivity of the climate response to any underlying uncertainties. This study uses a set of GGI low mitigation scenarios generated from the MESSAGE model (Riahi et al., 2007). The reduced-complexity climate and carbon cycle model ACC2 (Tanaka, 2008; Tanaka et al., 2009) is employed to calculate climate responses including associated uncertainty and to estimate geoengineering profiles to cap the warming at 2°C since preindustrial. The inversion setup for the model ACC2 is used to estimate the uncertain parameters (e.g. climate sensitivity) against associated historical observations (e.g. global-mean surface air temperature). Our preliminary results show that under climate and scenario uncertainties, a geoengineering intervention to avoid an overshoot would be with medium intensity in the latter half of this century (≈ 1 Mt. Pinatubo eruption every 4 years in terms of stratospheric sulfur injections). The start year of geoengineering intervention does not significantly influence the long-term geoengineering profile. However, a geoengineering intervention of the medium intensity could bring about substantial environmental side effects such as the destruction of stratospheric ozone. Our results point to the necessity to pursue persistently mainstream mitigation efforts. 2) Pollution Abatement and Geoengineering The second study examines the potential of geoengineering combined with air clean policy. A drastic air pollution abatement might result in an abrupt warming because it would suddenly remove the tropospheric aerosols which partly offset the background global warming (e.g. Andreae et al, 2005, Raddatz and Tanaka, 2010). This study investigates the magnitude of unrealized warming under a range of policy assumptions and associated uncertainties. Then the profile of geoengineering is estimated to suppress the warming that would be accompanied by clean air policy. This study is the first attempt to explore uncertainty in the warming caused by clean air policy - Kloster et al. (2009), which assess regional changes in climate and hydrological cycle, has not however included associated uncertainties in the analysis. A variety of policy assumptions will be devised to represent various degrees of air pollution abatement. These assumptions are used in the GAINS model to generate pollutants emissions scenarios. Such scenarios are combined with a set of GGI low mitigation scenarios and prescribed to the climate and carbon cycle model ACC2. ACC2 is employed to quantify the warming due to air pollution abatement and the geoengineering profile to avoid such a warming. Furthermore, the implications of such geoengineering interventions (e.g. ecosystem impact and adaptation capacity) are examined. References AMS (Americal Meteorological Society) (2009) A Policy Statement on 20 July 2009. http://www.ametsoc.org/policy/2009geoengineeringclimate_amsstatement.pdf Andreae (2005) Nature, 435, 1187-1190, doi:10.1038/nature03671. Crutzen (2006) Climatic Change, 77, 211-219. Kloster et al. (2009) Climate Dynamics, 33, doi:10.1007/s00382-009-0573-0. Meinshausen et al. (2009) Nature, 458, 1158-1162, doi:10.1038/nature08017. Raddatz and Tanaka (2010) Prepared for a re-submission to Geophysical Research Letters. Rasch et al. (2008) Philosophical Transactions of The Royal Society A, 366, 4007-4037, doi:10.1098/rsta.2008.0131. Riahi et al. (2007) Technological Forecasting and Social Change, 74, 887-935, doi:10.1016/j.techfore.2006.05.026. Robock (2008) Bulletin of the Atomic Scientists, 64, 14-18, doi: 10.2968/064002006. Tanaka (2008) Ph.D. thesis. International Max Planck Research School on Earth System Modelling, Hamburg, Germany. http://www.sub.uni-hamburg.de/opus/volltexte/2008/3654/ Tanaka et al. (2009) Geophysical Research Letters, 36, L16709, doi:10.1029/2009GL039642. Wigley (2008) Science, 314, 452-454, doi:10.1126/science.1131728.

Off the Shelf and Fueling the Public Discourse on America's Climate Choices

NASA Astrophysics Data System (ADS)

Ekwurzel, B.; Sideris, J.; Frumhoff, P.; Chung, C.

2010-12-01

To help ensure that the America’s Climate Choices (ACC) panel reports received constructive attention, The Union of Concerned Scientists and the National Academy of Sciences collaborated on a series of webinars to bring the findings of the reports to ca. 400 climate researchers, educators at academic and K-12 institutions, and experts from related fields. Panel chairs, report authors, and National Research Council study directors presented the findings and answered questions from participants across the nation. Attendees used the findings from ACC in their classrooms, community speaking engagements, and contact with policy makers. This presentation will provide a perspective on the scientific, policy and outreach strengths and challenges of the ACC reports - with a particular focus on opportunities to strengthen the communication of scientific assessments to key public and policymaker audiences in the distracted and complicated communications environment in which efforts to link robust assessments to decision-making now reside.

Impact of Parameterized Lateral Mixing on the Circulation of the Southern Ocean

NASA Astrophysics Data System (ADS)

Ragen, S.; Gnanadesikan, A.

2016-02-01

The Antarctic Circumpolar Current (ACC) is the strongest ocean current in the world, transporting approximately 130 Sv Eastward around Antarctica. This current is often poorly simulated in climate models. It is not clear why this is the case as the Circumpolar Current is affected by both wind and buoyancy. Changes in wind and buoyancy are not independent of each other, however, so determining the effects of both separately has proved difficult. This study was undertaken in order to examine the impact of changing the lateral diffusion coefficient A­redi on ACC transport. A­redi is poorly known and its value ranges across an order of magnitude in the current generation of climate models. To explore these dynamics, a coarse resolution, fully coupled model suite was run with A­redi mixing coefficients of 400 m2/s, 800 m2/s, 1200 m2/s, and 2400 m2/s. Additionally, two models were run with two-dimensional representations of the mixing coefficient based on altimetry. Our initial results indicate that higher values of the lateral mixing coefficient result in the following changes. We see weaker winds over the Southern Ocean as a whole. The high mixing case results in an 8.7% decrease in peak wind stress. We see a 2% weaker transport in the Drake Passage in the highest mixing case compared to the lowest, but an 11% decrease in transport for a zonal average. The change of temperature and salinity with depth with different Redi parameters also shows a significant difference between the Southern Ocean as a whole and the Drake Passage. Our findings seem to suggest that the Drake Passage is not an adequate diagnostic for explaining the differences between different climate models, as processes distant from the passage may play an important role. Observed changes in overturning with an increase in lateral mixing include an increase in northward transport of Antarctic Bottom Water fed by a small diversion of northern deep water inflows. This diversion means that less of the deep water is converted into surface water, consistent with weaker wind stresses.

Plants and climate change: complexities and surprises.

PubMed

Parmesan, Camille; Hanley, Mick E

2015-11-01

Anthropogenic climate change (ACC) will influence all aspects of plant biology over coming decades. Many changes in wild species have already been well-documented as a result of increased atmospheric CO2 concentrations, warming climate and changing precipitation regimes. A wealth of available data has allowed the use of meta-analyses to examine plant-climate interactions on more sophisticated levels than before. These analyses have revealed major differences in plant response among groups, e.g. with respect to functional traits, taxonomy, life-history and provenance. Interestingly, these meta-analyses have also exposed unexpected mismatches between theory, experimental, and observational studies. We reviewed the literature on species' responses to ACC, finding ∼42 % of 4000 species studied globally are plants (primarily terrestrial). We review impacts on phenology, distributions, ecophysiology, regeneration biology, plant-plant and plant-herbivore interactions, and the roles of plasticity and evolution. We focused on apparent deviations from expectation, and highlighted cases where more sophisticated analyses revealed that unexpected changes were, in fact, responses to ACC. We found that conventionally expected responses are generally well-understood, and that it is the aberrant responses that are now yielding greater insight into current and possible future impacts of ACC. We argue that inconclusive, unexpected, or counter-intuitive results should be embraced in order to understand apparent disconnects between theory, prediction, and observation. We highlight prime examples from the collection of papers in this Special Issue, as well as general literature. We found use of plant functional groupings/traits had mixed success, but that some underutilized approaches, such as Grime's C/S/R strategies, when incorporated, have improved understanding of observed responses. Despite inherent difficulties, we highlight the need for ecologists to conduct community-level experiments in systems that replicate multiple aspects of ACC. Specifically, we call for development of coordinating experiments across networks of field sites, both natural and man-made. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Beyond the bipolar seesaw: Toward a process understanding of interhemispheric coupling

NASA Astrophysics Data System (ADS)

Pedro, Joel B.; Jochum, Markus; Buizert, Christo; He, Feng; Barker, Stephen; Rasmussen, Sune O.

2018-07-01

The thermal bipolar ocean seesaw hypothesis was advanced by Stocker and Johnsen (2003) as the 'simplest possible thermodynamic model' to explain the time relationship between Dansgaard-Oeschger (DO) and Antarctic Isotope Maxima (AIM) events. In this review we combine palaeoclimate observations, theory and general circulation model experiments to advance from the conceptual model toward a process understanding of interhemispheric coupling and the forcing of AIM events. We present four main results: (1) Changes in Atlantic heat transport invoked by the thermal seesaw are partially compensated by opposing changes in heat transport by the global atmosphere and Pacific Ocean. This compensation is an integral part of interhemispheric coupling, with a major influence on the global pattern of climate anomalies. (2) We support the role of a heat reservoir in interhemispheric coupling but argue that its location is the global interior ocean to the north of the Antarctic Circumpolar Current (ACC), not the commonly assumed Southern Ocean. (3) Energy budget analysis indicates that the process driving Antarctic warming during AIM events is an increase in poleward atmospheric heat and moisture transport following sea ice retreat and surface warming over the Southern Ocean. (4) The Antarctic sea ice retreat is itself driven by eddy-heat fluxes across the ACC, amplified by sea-ice-albedo feedbacks. The lag of Antarctic warming after AMOC collapse reflects the time required for heat to accumulate in the ocean interior north of the ACC (predominantly the upper 1500 m), before it can be mixed across this dynamic barrier by eddies.

HIF1α in Tumorigenesis of Adenoid Cystic Carcinoma.

PubMed

Lim, Yun-Sung; Cha, Wonjae; Park, Min-Woo; Jeong, Woo-Jin; Ahn, Soon-Hyun

2017-02-01

Tumor hypoxia induces hypoxia-inducible factor-1α (HIF1α), which can influence tumorigenesis and metastasis. We evaluated the expression of HIF1α and the effect of HIF1α inhibitors in adenoid cystic carcinoma (ACC). HIF1α expression was demonstrated in ACC cell lines (ACC2 and ACCM). The effect of HIF1α inhibitors was evaluated. A systemic metastasis model was developed. The number of metastatic pulmonary nodules were analyzed. The ACCM cell line demonstrated greater HIF1α expression and invasion than ACC2. The expression of HIF1α and invasion of ACC cells were blocked by HIF1α siRNA. HIF1α inhibitors 17-N-allylamino-17-demethoxygeldanamycin (17AAG) and echinomycin inhibited cell invasion. 17AAG inhibited metastasis in the animal model, although not statistically significantly. HIF1α siRNA and 17AAG and echinomycin blocked invasion by ACC2 and ACCM cells. 17AAG exhibited therapeutic potential for inhibition of metastasis. Our results provide positive evidence that HIF1α is a promising research pathway for therapy of ACC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Formation of amorphous calcium carbonate in caves and its implications for speleothem research.

PubMed

Demény, Attila; Németh, Péter; Czuppon, György; Leél-Őssy, Szabolcs; Szabó, Máté; Judik, Katalin; Németh, Tibor; Stieber, József

2016-12-22

Speleothem deposits are among the most valuable continental formations in paleoclimate research, as they can be dated using absolute dating methods, and they also provide valuable climate proxies. However, alteration processes such as post-depositional mineralogical transformations can significantly influence the paleoclimatic application of their geochemical data. An innovative sampling and measurement protocol combined with scanning and transmission electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy is presented, demonstrating that carbonate precipitating from drip water in caves at ~10 °C contains amorphous calcium carbonate (ACC) that later transforms to nanocrystalline calcite. Stable oxygen isotope fractionations among calcite, ACC and water were also determined, proving that ACC is 18 O-depleted (by >2.4 ± 0.8‰) relative to calcite. This, in turn, has serious consequences for speleothem-based fluid inclusion research as closed system transformation of ACC to calcite may induce a negative oxygen isotope shift in fluid inclusion water, resulting in deterioration of the original compositions. ACC formation increases the speleothems' sensitivity to alteration as its interaction with external solutions may result in the partial loss of original proxy signals. Mineralogical analysis of freshly precipitating carbonate at the studied speleothem site is suggested in order to determine the potential influence of ACC formation.

Targeting MDM2 for Treatment of Adenoid Cystic Carcinoma

PubMed Central

Warner, Kristy A.; Nör, Felipe; Acasigua, Gerson A.; Martins, Manoela D.; Zhang, Zhaocheng; McLean, Scott A.; Spector, Matthew E.; Chepeha, Douglas B.; Helman, Joseph; Wick, Michael J.; Moskaluk, Christopher A.; Castilho, Rogerio M.; Pearson, Alexander T.; Wang, Shaomeng; Nör, Jacques E.

2016-01-01

Purpose There are no effective treatment options for patients with advanced adenoid cystic carcinoma (ACC). Here, we evaluated the effect of a new small molecule inhibitor of the MDM2-p53 interaction (MI-773) in preclinical models of ACC. Experimental Design To evaluate the anti-tumor effect of MI-773, we administered it to mice harboring 3 different patient-derived xenograft (PDX) models of ACC expressing functional p53. The effect of MI-773 on MDM2, p53, phospho-p53 and p21 was examined by Western blots in 5 low passage primary human ACC cell lines and in MI-773-treated PDX tumors. Results Single agent MI-773 caused tumor regression in the 3 PDX models of ACC studied here. For example, we observed a tumor growth inhibition (TGI) index of 127% in UM-PDX-HACC-5 tumors that was associated with an increase in the fraction of apoptotic cells (p=0.015). The number of p53-positive cells was increased in MI-773-treated PDX tumors (p<0.001), with a correspondent shift in p53 localization from the nucleus to the cytoplasm. Western blots demonstrated that MI-773 potently induced expression of p53 and its downstream targets p21, MDM2 and induced phosphorylation of p53 (serine 392) in low passage primary human ACC cells. Notably, MI-773 induced a dose-dependent increase in the fraction of apoptotic ACC cells and in the fraction of cells in the G1 phase of cell cycle (p<0.05). Conclusions Collectively, these data demonstrate that therapeutic inhibition of the MDM2-p53 interaction with MI-773 activates downstream effectors of apoptosis and causes robust tumor regression in preclinical models of adenoid cystic carcinoma. PMID:26936915

Predicting mortality after congenital heart surgeries: evaluation of the Aristotle and Risk Adjustement in Congenital Heart Surgery-1 risk prediction scoring systems: a retrospective single center analysis of 1150 patients.

PubMed

Joshi, Shreedhar S; Anthony, G; Manasa, D; Ashwini, T; Jagadeesh, A M; Borde, Deepak P; Bhat, Seetharam; Manjunath, C N

2014-01-01

To validate Aristotle basic complexity and Aristotle comprehensive complexity (ABC and ACC) and risk adjustment in congenital heart surgery-1 (RACHS-1) prediction models for in hospital mortality after surgery for congenital heart disease in a single surgical unit. Patients younger than 18 years, who had undergone surgery for congenital heart diseases from July 2007 to July 2013 were enrolled. Scoring for ABC and ACC scoring and assigning to RACHS-1 categories were done retrospectively from retrieved case files. Discriminative power of scoring systems was assessed with area under curve (AUC) of receiver operating curves (ROC). Calibration (test for goodness of fit of the model) was measured with Hosmer-Lemeshow modification of χ2 test. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were applied to assess reclassification. A total of 1150 cases were assessed with an all-cause in-hospital mortality rate of 7.91%. When modeled for multivariate regression analysis, the ABC (χ2 = 8.24, P = 0.08), ACC (χ2 = 4.17 , P = 0.57) and RACHS-1 (χ2 = 2.13 , P = 0.14) scores showed good overall performance. The AUC was 0.677 with 95% confidence interval (CI) of 0.61-0.73 for ABC score, 0.704 (95% CI: 0.64-0.76) for ACC score and for RACHS-1 it was 0.607 (95%CI: 0.55-0.66). ACC had an improved predictability in comparison to RACHS-1 and ABC on analysis with NRI and IDI. ACC predicted mortality better than ABC and RCAHS-1 models. A national database will help in developing predictive models unique to our populations, till then, ACC scoring model can be used to analyze individual performances and compare with other institutes.

Progression to Adrenocortical Tumorigenesis in Mice and Humans through Insulin-Like Growth Factor 2 and β-Catenin

PubMed Central

Heaton, Joanne H.; Wood, Michelle A.; Kim, Alex C.; Lima, Lorena O.; Barlaskar, Ferdous M.; Almeida, Madson Q.; Fragoso, Maria C.B.V.; Kuick, Rork; Lerario, Antonio M.; Simon, Derek P.; Soares, Ibere C.; Starnes, Elisabeth; Thomas, Dafydd G.; Latronico, Ana C.; Giordano, Thomas J.; Hammer, Gary D.

2013-01-01

Dysregulation of the WNT and insulin-like growth factor 2 (IGF2) signaling pathways has been implicated in sporadic and syndromic forms of adrenocortical carcinoma (ACC). Abnormal β-catenin staining and CTNNB1 mutations are reported to be common in both adrenocortical adenoma and ACC, whereas elevated IGF2 expression is associated primarily with ACC. To better understand the contribution of these pathways in the tumorigenesis of ACC, we examined clinicopathological and molecular data and used mouse models. Evaluation of adrenal tumors from 118 adult patients demonstrated an increase in CTNNB1 mutations and abnormal β-catenin accumulation in both adrenocortical adenoma and ACC. In ACC, these features were adversely associated with survival. Mice with stabilized β-catenin exhibited a temporal progression of increased adrenocortical hyperplasia, with subsequent microscopic and macroscopic adenoma formation. Elevated Igf2 expression alone did not cause hyperplasia. With the combination of stabilized β-catenin and elevated Igf2 expression, adrenal glands were larger, displayed earlier onset of hyperplasia, and developed more frequent macroscopic adenomas (as well as one carcinoma). Our results are consistent with a model in which dysregulation of one pathway may result in adrenal hyperplasia, but accumulation of a second or multiple alterations is necessary for tumorigenesis. PMID:22800756

PIG2LIG-4FUTURE: a database

NASA Astrophysics Data System (ADS)

El Ouahabi, A.; Martrat, B.; Lopez, J. F.; Grimalt, J. O.

2012-04-01

The ability to simulate the rhythm of abrupt climate changes (ACCs) will depend on the availability of high quality palæoclimate databases with sufficient temporal resolution to make relevant inferences from a human perspective. This study presents the PIG2LIG-4FUTURE database (P2L-4F db). The philosophy behind is to facilitate access to data not only for the scientific community, but also for those outside this community and, in doing so, ensure that the data are as useful as possible to help in answering a challenging key question: What is the risk of ACCs in periods similar to the present one? The P2L-4F db identifies an intra- and inter-event stratigraphy. A breakdown of the events in the PIG (present interglacial, time period from which more information is available and it is reasonably well dated) is defined in order to (2) identify ACCs in the LIG (last interglacial, much less known and dated period) for (4) better evaluation of the likelihood of sudden shifts within warm climate behaviour (i.e. next centuries, FUTURE). For this db, both the PIG and the LIG include deglaciation and interglacial states and they are referred to by means of chronostratigraphy: (i) the PIG refers to the last 19 ka years, i.e. a precessional cycle should be complete within the next 5 ka years; (ii) the LIG is the time span between 133 ka and 109 ka years, i.e. a time slot of 24 ka years, roughly a precessional cycle. The db compiles comprehensive selected palæo-data retrieved from a variety of sources (http://www.ncdc.noaa.gov, http://www.pangaea.de and others) but also instrumental data, to validate reconstructions against observations (e.g. http://data.giss.nasa.gov, http://iridl.ldeo.columbia.edu, etc). The records included accomplish two simple criteria: they cover the time span of interest, specifically the PIG and the LIG periods, and have sufficient time resolution to distinguish between an ACC and a gradual event. The research has focussed on three main palæoarchives: (i) ice cores, because they have been the reference for ACCs for over half a century; (ii) stalagmites, because they are crucial for dating, particularly for the LIG; (iii) marine and continental sediments, because they have proven to be a powerful source of ACCs. The same response is not seen everywhere due to proxy and location effects (see-saws not only north-to-south between poles, but also tropics-to-poles and eastern-to-western gradients). However, by using global and regional stacks, PIG-like events have been located within the LIG period. The spatio-temporal pattern during several specific events will be discussed. For example, the results show that the PIG 8.2 ka-event was something akin to a dividing line, as it was a LIG event which occured at approximately 120 ka ago. Environment and climate were evidently very different before and after this type of events. Additionally, the 2.6 ka and 0.8 ka-events were more an exception than a rule, somewhat resembling a clear glacial inception initiated from 113 to 111 ka ago. However, ACCs within the PIG are not exactly the same as the ones for the LIG, either in intensity or rates of change. This fact is hardly surprising given that none of the triggers and sources of persistence were reproduced in an identical mode during both periods.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singer, Jared W.; Yazaydin, A. O.; Kirkpatrick, Robert J.

Amorphous calcium carbonate (ACC) is a metastable precursor to crystalline CaCO{sub 3} phases that precipitates by aggregation of ion pairs and prenucleation clusters. We use {sup 43}Ca solid-state NMR spectroscopy to probe the local structure and transformation of ACC synthesized from seawater-like solutions with and without Mg{sup 2+} and computational molecular dynamics (MD) simulations to provide more detailed molecular-scale understanding of the ACC structure. The {sup 43}Ca NMR spectra of ACC collected immediately after synthesis consist of broad, featureless resonances with Gaussian line shapes (FWHH = 27.6 {+-} 1 ppm) that do not depend on Mg{sup 2+} or H{sub 2}Omore » content. A correlation between {sup 43}Ca isotropic chemical shifts and mean Ca-O bond distances for crystalline hydrous and anhydrous calcium carbonate phases indicates indistinguishable maximum mean Ca-O bond lengths of {approx}2.45 {angstrom} for all our samples. This value is near the upper end of the published Ca-O bond distance range for biogenic and synthetic ACCs obtained by Ca-X-ray absorption spectroscopy. It is slightly smaller than the values from the structural model of Mgfree ACC by Goodwin et al. obtained from reverse Monte Carlo (RMC) modeling of X-ray scattering data and our own computational molecular dynamics (MD) simulation based on this model. An MD simulation starting with the atomic positions of the Goodwin et al. RMC model using the force field of Raiteri and Gale shows significant structural reorganization during the simulation and that the interconnected carbonate/water-rich channels in the Goodwin et al. model shrink in size over the 2 ns simulation time. The distribution of polyhedrally averaged Ca-O bond distances from the MD simulation is in good agreement with the {sup 43}Ca NMR peak shape, suggesting that local structural disorder dominates the experimental line width of ACC.« less

Antarctic Circumpolar Current Transport Variability during 2003-05 from GRACE

NASA Technical Reports Server (NTRS)

Zlotnicki, Victor; Wahr, John; Fukumori, Ichiro; Song, Yuhe T.

2006-01-01

Gravity Recovery and Climate Experiment (GRACE) gravity data spanning January 2003 - November 2005 are used as proxies for ocean bottom pressure (BP) averaged over 1 month, spherical Gaussian caps 500 km in radius, and along paths bracketing the Antarctic Circumpolar Current's various fronts. The GRACE BP signals are compared with those derived from the Estimating the Circulation and Climate of the Ocean (ECCO) ocean modeling-assimilation system, and to a non-Boussinesq version of the Regional Ocean Model System (ROMS). The discrepancy found between GRACE and the models is 1.7 cm(sub H2O) (1 cm(sub H2O) similar to 1 hPa), slightly lower than the 1.9 cm(sub H2O) estimated by the authors independently from propagation of GRACE errors. The northern signals are weak and uncorrelated among basins. The southern signals are strong, with a common seasonality. The seasonal cycle GRACE data observed in the Pacific and Indian Ocean sectors of the ACC are consistent, with annual and semiannual amplitudes of 3.6 and 0.6 cm(sub H2O) (1.1 and 0.6 cm(sub H2O) with ECCO), the average over the full southern path peaks (stronger ACC) in the southern winter, on days of year 197 and 97 for the annual and semiannual components, respectively; the Atlantic Ocean annual peak is 20 days earlier. An approximate conversion factor of 3.1 Sv ( Sv equivalent to 10(exp 6) m(exp 3) s(exp -1)) of barotropic transport variability per cm(sub H2O) of BP change is estimated. Wind stress data time series from the Quick Scatterometer (QuikSCAT), averaged monthly, zonally, and over the latitude band 40 de - 65 deg S, are also constructed and subsampled at the same months as with the GRACE data. The annual and semiannual harmonics of the wind stress peak on days 198 and 82, respectively. A decreasing trend over the 3 yr is observed in the three data types.

Antarctic Circumpolar Current Transport Variability during 2003-05 from GRACE

NASA Technical Reports Server (NTRS)

Zlotnicki, Victor; Wahr, John; Fukumori, Ichiro; Song, Yuhe T.

2007-01-01

Gravity Recovery and Climate Experiment (GRACE) gravity data spanning January 2003-November 2005 are used as proxies for ocean bottom pressure (BP) averaged over 1 month, spherical Gaussian caps 500 km in radius, and along paths bracketing the Antarctic Circumpolar Current's various fronts. The GRACE BP signals are compared with those derived from the Estimating the Circulation and Climate of the Ocean (ECCO) ocean modeling-assimilation system, and to a non-Boussinesq version of the Regional Ocean Model System (ROMS). The discrepancy found between GRACE and the models is 1.7 cmH2O (1 cmH2O approx. 1 hPa), slightly lower than the 1.9 cmH2O estimated by the authors independently from propagation of GRACE errors. The northern signals are weak and uncorrelated among basins. The southern signals are strong, with a common seasonality. The seasonal cycle GRACE data observed in the Pacific and Indian Ocean sectors of the ACC are consistent, with annual and semiannual amplitudes of 3.6 and 0.6 cmH2O (1.1 and 0.6 cmH2O with ECCO), the average over the full southern path peaks (stronger ACC) in the southern winter, on days of year 197 and 97 for the annual and semiannual components, respectively; the Atlantic Ocean annual peak is 20 days earlier. An approximate conversion factor of 3.1 Sv (Sv equiv 10(exp 6)cu m/s) of barotropic transport variability per cmH2O of BP change is estimated. Wind stress data time series from the Quick Scatterometer (QuikSCAT), averaged monthly, zonally, and over the latitude band 40(deg)- 65(deg)S, are also constructed and subsampled at the same months as with the GRACE data. The annual and semiannual harmonics of the wind stress peak on days 198 and 82, respectively. A decreasing trend over the 3 yr is observed in the three data types.

Evaluating Antarctic sea ice predictability at seasonal to interannual timescales in global climate models

NASA Astrophysics Data System (ADS)

Marchi, Sylvain; Fichefet, Thierry; Goosse, Hugues; Zunz, Violette; Tietsche, Steffen; Day, Jonny; Hawkins, Ed

2016-04-01

Unlike the rapid sea ice losses reported in the Arctic, satellite observations show an overall increase in Antarctic sea ice extent over recent decades. Although many processes have already been suggested to explain this positive trend, it remains the subject of current investigations. Understanding the evolution of the Antarctic sea ice turns out to be more complicated than for the Arctic for two reasons: the lack of observations and the well-known biases of climate models in the Southern Ocean. Irrespective of those issues, another one is to determine whether the positive trend in sea ice extent would have been predictable if adequate observations and models were available some decades ago. This study of Antarctic sea ice predictability is carried out using 6 global climate models (HadGEM1.2, MPI-ESM-LR, GFDL CM3, EC-Earth V2, MIROC 5.2 and ECHAM 6-FESOM) which are all part of the APPOSITE project. These models are used to perform hindcast simulations in a perfect model approach. The predictive skill is estimated thanks to the PPP (Potential Prognostic Predictability) and the ACC (Anomaly Correlation Coefficient). The former is a measure of the uncertainty of the ensemble while the latter assesses the accuracy of the prediction. These two indicators are applied to different variables related to sea ice, in particular the total sea ice extent and the ice edge location. This first model intercomparison study about sea ice predictability in the Southern Ocean aims at giving a general overview of Antarctic sea ice predictability in current global climate models.

Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening

PubMed Central

LING, SHIZHANG; RETTIG, ELENI M.; TAN, MARIETTA; CHANG, XIAOFEI; WANG, ZHIMING; BRAIT, MARIANA; BISHOP, JUSTIN A.; FERTIG, ELANA J.; CONSIDINE, MICHAEL; WICK, MICHAEL J.; HA, PATRICK K.

2016-01-01

Salivary gland adenoid cystic carcinoma (ACC) is a rare head and neck malignancy without molecular biomarkers that can be used to predict the chemotherapeutic response or prognosis of ACC. The regulation of gene expression of oncogenes and tumor suppressor genes (TSGs) through DNA promoter methylation may play a role in the carcinogenesis of ACC. To identify differentially methylated genes in ACC, a global demethylating agent, 5-aza-2′-deoxycytidine (5-AZA) was utilized to unmask putative TSG silencing in ACC xenograft models in mice. Fresh xenografts were passaged, implanted in triplicate in mice that were treated with 5-AZA daily for 28 days. These xenografts were then evaluated for genome-wide DNA methylation patterns using the Illumina Infinium HumanMethylation27 BeadChip array. Validation of the 32 candidate genes was performed by bisulfite sequencing (BS-seq) in a separate cohort of 6 ACC primary tumors and 6 normal control salivary gland tissues. Hypermethylation was identified in the HCN2 gene promoter in all 6 control tissues, but hypomethylation was found in all 6 ACC tumor tissues. Quantitative validation of HCN2 promoter methylation level in the region detected by BS-seq was performed in a larger cohort of primary tumors (n=32) confirming significant HCN2 hypomethylation in ACCs compared with normal samples (n=10; P=0.04). HCN2 immunohistochemical staining was performed on an ACC tissue microarray. HCN2 staining intensity and H-score, but not percentage of the positively stained cells, were significantly stronger in normal tissues than those of ACC tissues. With our novel screening and sequencing methods, we identified several gene candidates that were methylated. The most significant of these genes, HCN2, was actually hypomethylated in tumors. However, promoter methylation status does not appear to be a major determinant of HCN2 expression in normal and ACC tissues. HCN2 hypomethylation is a biomarker of ACC and may play an important role in the carcinogenesis of ACC. PMID:27212063

Models for Amorphous Calcium Carbonate

NASA Astrophysics Data System (ADS)

Sinha, Sourabh

Many species e.g. sea urchin form amorphous calcium carbonate (ACC) precursor phases that subsequently transform into crystalline CaCO3. It is certainly possible that the biogenic ACC might have more than 10 wt% Mg and ˜3 wt% of water. The structure of ACC and the mechanisms by which it transforms to crystalline phase are still poorly understood. In this dissertation our goal is to determine an atomic structure model that is consistent with diffraction and IR measurements of ACC. For this purpose a calcite supercell with 24 formula units, containing 120 atoms, was constructed. Various configurations with substitution of Ca by 6 Mg ions (6 wt.%) and insertion of 3-5 H 2O molecules (2.25-3.75 wt.%) in the interstitial positions of the supercell, were relaxed using a robust density function code VASP. The most noticeable effects were the tilts of CO3 groups and the distortion of Ca sub-lattice, especially in the hydrated case. The distributions of Ca-Ca nearest neighbor distance and CO3 tilts were extracted from various configurations. The same methods were also applied to aragonite. Sampling from the calculated distortion distributions, we built models for amorphous calcite/aragonite of size ˜ 1700 nm3 based on a multi-scale modeling scheme. We used these models to generate diffraction patterns and profiles with our diffraction code. We found that the induced distortions were not enough to generate a diffraction profile typical of an amorphous material. We then studied the diffraction profiles from several nano-crystallites as recent studies suggest that ACC might be a random array of nano-cryatallites. It was found that the generated diffraction profile from a nano-crystallite of size ˜ 2 nm3 is similar to that from the ACC.

The CEOS Atmospheric Composition Constellation (ACC), an Integrated Observing System

NASA Astrophysics Data System (ADS)

Hilsenrath, E.; Langen, J.; Zehner, C.

2008-05-01

The Atmospheric Composition (AC) Constellation is one of four pilot projects initiated by the Committee for Earth Observations Systems (CEOS) to bring about technical/scientific cooperation among space agencies that meet the goals of GEO and comply with the CEOS member agencies national programs. The Constellation concept has been endorsed in the GEO Work Plan, 2007-2009. The AC Constellation goal is to collect and deliver data to develop and improve monitoring, assessment and predictive capabilities for changes in the ozone layer, air quality and climate forcing associated with changes in the environment. These data will support five of the nine GEO SBAs: Health, Energy, Climate, Hazards, and Ecosystems. At the present time ESA, EC, CSA, CNES, JAXA, DLR, NIVR, NASA, NOAA and Eumetsat are participating in the Constellation study, and have major assets in orbit including 17 instruments on seven platforms. One goal of the Constellation study is to identify missing capabilities that will result when the present orbiting research satellites missions end and those not included in the next generation operational missions. Missing observations include very accurate and high spatial resolution measurements needed to be to track trends in atmospheric composition and understand their relationship to climate change. The following are the top level objectives for the AC Constellation Concept Study: • Develop a virtual constellation of existing and upcoming missions using synergies among the instruments and identify missing capabilities. • Study advanced architecture with new space assets and varying orbits with expectations that new technology could also be brought forward to best meet user requirements • Data system interoperability to insure that data are useful, properly targeted, and easily accessible. To demonstrate that the Constellation concept can provide value added data products, the ACC has initiated the three projects that are being supported by the participating space agencies. These include 1) Time of day changes in NO2 using Aura/OMI and Metop/GOME-2. 2) Near-real-time fire detection and smoke forecasts using multiple satellites (A-Train, GOES, GOME-2, MSG, etc) and trajectory model, and 3) Improved volcanic ash alerts for aviation hazard avoidance from satellite SO2 and ash data from SCIAMACHY, OMI, GOME-2, AIRS and SEVIRI. Each of the three projects will address the GEO SBAs with consideration to discovery and interoperability of their data products. The status of the ACC studies will be reviewed with a progress report on the above three projects.

Origin, signature and palaeoclimatic influence of the Antarctic Circumpolar Current

NASA Astrophysics Data System (ADS)

Barker, P. F.; Thomas, E.

2004-06-01

The Antarctic Circumpolar Current (ACC) is today the strongest current in the world's ocean, with a significant influence on global climate. Its assumed history and influence on palaeoclimate, while almost certainly equally profound, are here called into question. In this paper, we review 30 years of accumulated data, interpretation and speculation about the ACC, deriving mainly from DSDP and ODP drilling in the Southern Ocean. For most of this time, a conventional view of ACC development, signature and influence has held sway among palaeoceanographers and marine geologists. In this view, the ACC began at about 34 Ma, close to the Eocene-Oligocene boundary, the time of onset of significant Antarctic glaciation and the time of creation of a deep-water gap (Tasmanian Seaway) between Australia and Antarctica as the South Tasman Rise separated from North Victoria Land. This is the "smoking gun" of synchroneity. The Southern Ocean sediment record shows a latest Eocene development and subsequent geographic expansion of a siliceous biofacies, its northern limit taken to indicate the palaeo-position of the ACC axis. In addition, the ACC was considered to have caused Antarctic glaciation by isolating the continent within a cold-water annulus, reducing north-south heat transport. A different (and later) date for Antarctic-South American opening ("Drake Passage") was proposed, but the timing of ACC onset there was disputed, and the simple story survived. Recent developments, however, call it into question. Modern physical oceanography shows that all or most of present-day ACC transport is confined to narrow jets within deep-reaching circumpolar fronts, and numerical modelling has suggested that a steady reduction in greenhouse gas concentration through the Cenozoic could cause Antarctic glaciation, with or without a contribution from ocean circulation change. The rapidity of Antarctic glacial onset at the Eocene-Oligocene boundary and coeval creation of a deep-water gap south of Tasmania both survive but, in light of the new information, the presence of a siliceous biofacies cannot be claimed as evidence of the existence of a continuous, deep-reaching oceanic front and therefore of an ACC, and the possibility arises that cool and cold sea-surface temperatures were effects of Antarctic glaciation rather than evidence of a major contributor to its cause. In considering future work, we emphasise the importance of additional information from ancillary fields—better definition of the necessary and sufficient properties of oceanic fronts, additional determinations of Cenozoic atmospheric pCO 2 and further developments in models of Antarctic glaciation—but also suggest the way forward in marine geology. Our knowledge of the development and palaeoclimatic significance of the ACC will be best served by grain-size studies of bottom current strength at selected locations, and geochemical or mineralogical studies of clays and IRD as a way of examining provenance and therefore surface and bottom current directions and the existence of interocean connections. Studies of biogenic assemblages within the same sediments may be able to recover a value for the many such studies undertaken in the past and interpreted, probably erroneously, as evidence for an ACC. Mainly in view of the timing uncertainties, we propose the region south of South America as the best initial focus of future investigation.

A structural and functional model for the 1-aminocyclopropane-1-carboxylic acid oxidase.

PubMed

Sallmann, Madleen; Oldenburg, Fabio; Braun, Beatrice; Réglier, Marius; Simaan, A Jalila; Limberg, Christian

2015-10-12

The hitherto most realistic low-molecular-weight analogue for the 1-aminocyclopropane-1-carboxylic acid oxidase (ACCO) is reported. The ACCOs 2-His-1-carboxylate iron(II) active site was mimicked by a TpFe moiety, to which the natural substrate ACC could be bound. The resulting complex [Tp(Me,Ph) FeACC] (1), according to X-ray diffraction analysis performed for the nickel analogue, represents an excellent structural model, featuring ACC coordinated in a bidentate fashion-as proposed for the enzymatic substrate complex-as well as a vacant coordination site that forms the basis for the first successful replication also of the ACCO function: 1 is the first known ACC complex that reacts with O2 to produce ethylene. As a FeOOH species had been suggested as intermediate in the catalytic cycle, H2 O2 was tested as the oxidant, too, and indeed evolution of ethylene proceeded even more rapidly to give 65 % yield. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antarctic Circumpolar Current Dynamics and Their Relation to Antarctic Ice Sheet and Perennial Sea-Ice Variability in the Central Drake Passage During the Last Climate Cycle

NASA Astrophysics Data System (ADS)

Kuhn, G.; Wu, S.; Hass, H. C.; Klages, J. P.; Zheng, X.; Arz, H. W.; Esper, O.; Hillenbrand, C. D.; Lange, C.; Lamy, F.; Lohmann, G.; Müller, J.; McCave, I. N. N.; Nürnberg, D.; Roberts, J.; Tiedemann, R.; Timmermann, A.; Titschack, J.; Zhang, X.

2017-12-01

The evolution of the Antarctic Ice Sheet during the last climate cycle and the interrelation to global atmospheric and ocean circulation remains controversial and plays an important role for our understanding of ice sheet response to modern global warming. The timing and sequence of deglacial warming is relevant for understanding the variability and sensitivity of the Antarctic Ice Sheet to climatic changes, and the continuing rise of atmospheric greenhouse gas concentrations. The Antarctic Ice Sheet is a pivotal component of the global water budget. Freshwater fluxes from the ice sheet may affect the Antarctic Circumpolar Current (ACC), which is strongly impacted by the westerly wind belt in the Southern Hemisphere (SHWW) and constricted to its narrowest extent in the Drake Passage. The flow of ACC water masses through Drake Passage is, therefore, crucial for advancing our understanding of the Southern Ocean's role in global meridional overturning circulation and global climate change. In order to address orbital and millennial-scale variability of the Antarctic ice sheet and the ACC, we applied a multi-proxy approach on a sediment core from the central Drake Passage including grain size, iceberg-rafted debris, mineral dust, bulk chemical and mineralogical composition, and physical properties. In combination with already published and new sediment records from the Drake Passage and Scotia Sea, as well as high-resolution data from Antarctic ice cores (WDC, EDML), we now have evidence that during glacial times a more northerly extent of the perennial sea-ice zone decreased ACC current velocities in the central Drake Passage. During deglaciation the SHWW shifted southwards due to a decreasing temperature gradient between subtropical and polar latitudes caused by sea ice and ice sheet decline. This in turn caused Southern Hemisphere warming, a more vigorous ACC, stronger Southern Ocean ventilation, and warm Circumpolar Deep Water (CDW) upwelling on Antarctic shelves resulting in increased ice shelf melting. Stronger upwelling is associated with a rise in atmospheric carbon dioxide to reach a threshold at which full deglaciation could become inevitable.

Modelling galaxy clustering: halo occupation distribution versus subhalo matching.

PubMed

Guo, Hong; Zheng, Zheng; Behroozi, Peter S; Zehavi, Idit; Chuang, Chia-Hsun; Comparat, Johan; Favole, Ginevra; Gottloeber, Stefan; Klypin, Anatoly; Prada, Francisco; Rodríguez-Torres, Sergio A; Weinberg, David H; Yepes, Gustavo

2016-07-01

We model the luminosity-dependent projected and redshift-space two-point correlation functions (2PCFs) of the Sloan Digital Sky Survey (SDSS) Data Release 7 Main galaxy sample, using the halo occupation distribution (HOD) model and the subhalo abundance matching (SHAM) model and its extension. All the models are built on the same high-resolution N -body simulations. We find that the HOD model generally provides the best performance in reproducing the clustering measurements in both projected and redshift spaces. The SHAM model with the same halo-galaxy relation for central and satellite galaxies (or distinct haloes and subhaloes), when including scatters, has a best-fitting χ 2 /dof around 2-3. We therefore extend the SHAM model to the subhalo clustering and abundance matching (SCAM) by allowing the central and satellite galaxies to have different galaxy-halo relations. We infer the corresponding halo/subhalo parameters by jointly fitting the galaxy 2PCFs and abundances and consider subhaloes selected based on three properties, the mass M acc at the time of accretion, the maximum circular velocity V acc at the time of accretion, and the peak maximum circular velocity V peak over the history of the subhaloes. The three subhalo models work well for luminous galaxy samples (with luminosity above L * ). For low-luminosity samples, the V acc model stands out in reproducing the data, with the V peak model slightly worse, while the M acc model fails to fit the data. We discuss the implications of the modelling results.

Reducing the risk of rear-end collisions with infrastructure-to-vehicle (I2V) integration of variable speed limit control and adaptive cruise control system.

PubMed

Li, Ye; Wang, Hao; Wang, Wei; Liu, Shanwen; Xiang, Yun

2016-08-17

Adaptive cruise control (ACC) has been investigated recently to explore ways to increase traffic capacity, stabilize traffic flow, and improve traffic safety. However, researchers seldom have studied the integration of ACC and roadside control methods such as the variable speed limit (VSL) to improve safety. The primary objective of this study was to develop an infrastructure-to-vehicle (I2V) integrated system that incorporated both ACC and VSL to reduce rear-end collision risks on freeways. The intelligent driver model was firstly modified to simulate ACC behavior and then the VSL strategy used in this article was introduced. Next, the I2V system was proposed to integrate the 2 advanced techniques, ACC and VSL. Four scenarios of no control, VSL only, ACC only, and the I2V system were tested in simulation experiments. Time exposed time to collision (TET) and time integrated time to collision (TIT), 2 surrogate safety measures derived from time to collision (TTC), were used to evaluate safety issues associated with rear-end collisions. The total travel times of each scenario were also compared. The simulation results indicated that both the VSL-only and ACC-only methods had a positive impact on reducing the TET and TIT values (reduced by 53.0 and 58.6% and 59.0 and 65.3%, respectively). The I2V system combined the advantages of both ACC and VSL to achieve the most safety benefits (reduced by 71.5 and 77.3%, respectively). Sensitivity analysis of the TTC threshold also showed that the I2V system obtained the largest safety benefits with all of the TTC threshold values. The impact of different market penetration rates of ACC vehicles in I2V system indicated that safety benefits increase with an increase in ACC proportions. Compared to VSL-only and ACC-only scenarios, this integrated I2V system is more effective in reducing rear-end collision risks. The findings of this study provide useful information for traffic agencies to implement novel techniques to improve safety on freeways.

A Future Accelerated Cognitive Distributed Hybrid Testbed for Big Data Science Analytics

NASA Astrophysics Data System (ADS)

Halem, M.; Prathapan, S.; Golpayegani, N.; Huang, Y.; Blattner, T.; Dorband, J. E.

2016-12-01

As increased sensor spectral data volumes from current and future Earth Observing satellites are assimilated into high-resolution climate models, intensive cognitive machine learning technologies are needed to data mine, extract and intercompare model outputs. It is clear today that the next generation of computers and storage, beyond petascale cluster architectures, will be data centric. They will manage data movement and process data in place. Future cluster nodes have been announced that integrate multiple CPUs with high-speed links to GPUs and MICS on their backplanes with massive non-volatile RAM and access to active flash RAM disk storage. Active Ethernet connected key value store disk storage drives with 10Ge or higher are now available through the Kinetic Open Storage Alliance. At the UMBC Center for Hybrid Multicore Productivity Research, a future state-of-the-art Accelerated Cognitive Computer System (ACCS) for Big Data science is being integrated into the current IBM iDataplex computational system `bluewave'. Based on the next gen IBM 200 PF Sierra processor, an interim two node IBM Power S822 testbed is being integrated with dual Power 8 processors with 10 cores, 1TB Ram, a PCIe to a K80 GPU and an FPGA Coherent Accelerated Processor Interface card to 20TB Flash Ram. This system is to be updated to the Power 8+, an NVlink 1.0 with the Pascal GPU late in 2016. Moreover, the Seagate 96TB Kinetic Disk system with 24 Ethernet connected active disks is integrated into the ACCS storage system. A Lightweight Virtual File System developed at the NASA GSFC is installed on bluewave. Since remote access to publicly available quantum annealing computers is available at several govt labs, the ACCS will offer an in-line Restricted Boltzmann Machine optimization capability to the D-Wave 2X quantum annealing processor over the campus high speed 100 Gb network to Internet 2 for large files. As an evaluation test of the cognitive functionality of the architecture, the following studies utilizing all the system components will be presented; (i) a near real time climate change study generating CO2 fluxes and (ii) a deep dive capability into an 8000 x8000 pixel image pyramid display and (iii) Large dense and sparse eigenvalue decomposition.

Modeling the adsorption of metal ions (Cu 2+, Ni 2+, Pb 2+) onto ACCs using surface complexation models

NASA Astrophysics Data System (ADS)

Faur-Brasquet, Catherine; Reddad, Zacaria; Kadirvelu, Krishna; Le Cloirec, Pierre

2002-08-01

Activated carbon cloths (ACCs), whose efficiency has been demonstrated for microorganics adsorption from water, were here studied in the removal of metal ions from aqueous solution. Two ACCs are investigated, they are characterized in terms of porosity parameters (BET specific surface area, percentage of microporosity) and chemical characteristics (acidic surface groups, acidity constants, point of zero charge). A first part consists in the experimental study of three metal ions removal (Cu 2+, Ni 2+ and Pb 2+) in a batch reactor. Isotherms modeling by Freundlich and Brunauer-Emmett-Teller (BET) equations enables the following adsorption order: Cu 2+>Ni 2+>Pb 2+ to be determined for adsorption capacities on a molar basis. It may be related to adsorbates characteristics in terms of electronegativity and ionic radius. The influence of adsorbent's microporosity is also shown. Adsorption experiments carried out for pH values ranging from 2 to 10 demonstrate: (i) an adsorption occurring below the precipitation pH; (ii) the strong influence of pH, with a decrease of electrostatic repulsion due to the formation of less charged hydrolyzed species coupled with a decrease of activated carbon surface charge as pH increases. The second part focuses on the modeling of adsorption versus the pH experimental data by the diffuse layer model (DLM) using Fiteql software. The model is efficient to describe the system behavior in the pH range considered. Regarding complexation constants, they show the following affinity for ACC: Pb 2+>Cu 2+>Ni 2+. They are related to initial concentrations used for the three metal ions.

Application of a GCM Ensemble Seasonal Climate Forecasts to Crop Yield Prediction in East Africa

NASA Astrophysics Data System (ADS)

Ogutu, G.; Franssen, W.; Supit, I.; Hutjes, R. W. A.

2016-12-01

We evaluated the potential use of ECMWF System-4 seasonal climate forecasts (S4) for impacts analysis over East Africa. Using the 15 member, 7 months ensemble forecasts initiated every month for 1981-2010, we tested precipitation (tp), air temperature (tas) and surface shortwave radiation (rsds) forecast skill against the WATCH forcing Data ERA-Interim (WFDEI) re-analysis and other data. We used these forecasts as input in the WOFOST crop model to predict maize yields. Forecast skill is assessed using anomaly correlation (ACC), Ranked Probability Skill Score (RPSS) and the Relative Operating Curve Skill Score (ROCSS) for MAM, JJA and OND growing seasons. Predicted maize yields (S4-yields) are verified against historical observed FAO and nationally reported (NAT) yield statistics, and yields from the same crop model forced by WFDEI (WFDEI-yields). Predictability of the climate forecasts vary with season, location and lead-time. The OND tp forecasts show skill over a larger area up to three months lead-time compared to MAM and JJA. Upper- and lower-tercile tp forecasts are 20-80% better than climatology. Good tas forecast skill is apparent with three months lead-time. The rsds is less skillful than tp and tas in all seasons when verified against WFDEI but higher against others. S4-forecasts captures ENSO related anomalous years with region dependent skill. Anomalous ENSO influence is also seen in simulated yields. Focussing on the main sowing dates in the northern (July), equatorial (March-April) and southern (December) regions, WFDEI-yields are lower than FAO and NAT but anomalies are comparable. Yield anomalies are predictable 3-months before sowing in most of the regions. Differences in interannual variability in the range of ±40% may be related to sensitivity of WOFOST to drought stress while the ACCs are largely positive ranging from 0.3 to 0.6. Above and below-normal yields are predictable with 2-months lead time. We evidenced a potential use of seasonal climate forecasts with a crop simulation model to predict anomalous maize yields over East Africa. The findings open a window to better use of climate forecasts in food security early warning systems, and pre-season policy and farm management decisions.

ETHY. A theory of fruit climacteric ethylene emission.

PubMed

Génard, Michel; Gouble, Barbara

2005-09-01

A theory of fruit climacteric ethylene emission was developed and used as the basis of a simulation model called ETHY. According to the theory, the biosynthetic pathway of ethylene is supplied by ATP and is regulated by 1-aminocyclopropane-1-carboxylic acid (ACC) synthase and ACC oxidase. The conjugation of ACC with malonate to form MACC was taken into account as a way to decrease the availability of ACC. Because of the seasonal increase of fruit volume, the dilution of biochemical compounds used in ETHY was taken into account. Finally, the ethylene diffusion across the skin was considered. The theory took into account the effect of temperature and O(2) and CO(2) internal concentrations on ethylene. The model was applied to peach (Prunus persica) fruit over 3 years, several leaf:fruit ratios, and irrigation conditions. An adequate ethylene increase was predicted without considering any increase in respiration during the ripening period, which suggests that the respiratory climacteric may not be required for ripening. Another important result of this study is the high sensitivity of ETHY to the parameters involved in the calculation of ACC oxidase and ACC synthase activities, ATP production, and skin surface and permeability. ETHY was also highly sensitive to changes in fruit growth and temperature.

ETHY. A Theory of Fruit Climacteric Ethylene Emission1

PubMed Central

Génard, Michel; Gouble, Barbara

2005-01-01

A theory of fruit climacteric ethylene emission was developed and used as the basis of a simulation model called ETHY. According to the theory, the biosynthetic pathway of ethylene is supplied by ATP and is regulated by 1-aminocyclopropane-1-carboxylic acid (ACC) synthase and ACC oxidase. The conjugation of ACC with malonate to form MACC was taken into account as a way to decrease the availability of ACC. Because of the seasonal increase of fruit volume, the dilution of biochemical compounds used in ETHY was taken into account. Finally, the ethylene diffusion across the skin was considered. The theory took into account the effect of temperature and O2 and CO2 internal concentrations on ethylene. The model was applied to peach (Prunus persica) fruit over 3 years, several leaf:fruit ratios, and irrigation conditions. An adequate ethylene increase was predicted without considering any increase in respiration during the ripening period, which suggests that the respiratory climacteric may not be required for ripening. Another important result of this study is the high sensitivity of ETHY to the parameters involved in the calculation of ACC oxidase and ACC synthase activities, ATP production, and skin surface and permeability. ETHY was also highly sensitive to changes in fruit growth and temperature. PMID:16143642

Serotonin2C receptors in the nucleus accumbens are involved in enhanced alcohol-drinking behavior

PubMed Central

Yoshimoto, Kanji; Watanabe, Yoshihisa; Tanaka, Masaki; Kimura, Minoru

2012-01-01

Dopamine and serotonin (5-HT) in the nucleus accumbens (ACC) and ventral tegmental area of the mesoaccumbens reward pathways have been implicated in the mechanisms underlying development of alcohol dependence. We used a C57BL/6J mouse model with increased voluntary alcohol-drinking behavior by exposing the mice to alcohol vapor for 20 consecutive days. In the alcohol-exposed mice, the expression of 5-HT2C receptor mRNA increased in the ACC, caudate nucleus and putamen, dorsal raphe nucleus (DRN), hippocampus and lateral hypothalamus, while the protein level of 5-HT2C receptor significantly increased in the ACC. The expression of 5-HT7 receptor mRNA increased in the ACC and DRN. Contents of 5-HT decreased in the ACC shell (ACCS) and DRN of the alcohol-exposed mice. The basal extracellular releases of dopamine (DA) and 5-HT in the ACCS increased more in the alcohol-exposed mice than in alcohol-naïve mice. The magnitude of the alcohol-induced ACCS DA and 5-HT release in the alcohol-exposed mice was increased compared with the control mice. Intraperitoneal (i.p.) administration or local injection into ACCS of the 5-HT2C receptor antagonist, SB-242084, suppressed voluntary alcohol-drinking behavior in the alcohol-exposed mice. But the i.p. administration of the 5-HT7 receptor antagonist, SB-258719, did not have significant effects on alcohol-drinking behavior in the alcohol-exposed mice. The effects of the 5-HT2C receptor antagonist were not observed in the air-exposed control mice. These results suggest that adaptations of the 5-HT system, especially the upregulation of 5-HT2C receptors in the ACCS, are involved in the development of enhanced voluntary alcohol-drinking behavior. PMID:22512261

Exploitation of agro-climatic environment for selection of 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase producing salt tolerant indigenous plant growth promoting rhizobacteria.

PubMed

Misra, Sankalp; Dixit, Vijay Kant; Khan, Mohammad Haneef; Kumar Mishra, Shashank; Dviwedi, Gyanendra; Yadav, Sumit; Lehri, Alok; Singh Chauhan, Puneet

2017-12-01

A comprehensive survey for 09 agro-climatic zones of Uttar Pradesh, India was conducted to isolate and characterize salt tolerant 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase possessing plant growth promoting (PGP) rhizobacteria for salt stress amelioration in rice. Here, we have isolated 1125 bacteria having the ability to tolerate 1M NaCl and out of those, 560 were screened for utilizing ACC as sole nitrogen source. 560 isolates were subjected for bacteria coated seed germination assay under 100mM salt (NaCl) stress resulting to 77 isolates which were further evaluated for seed germination assay, PGP and abiotic stress tolerance ability in vitro. This evaluation revealed 15 potent rhizobacteria representing each agro-climatic zone and salt stress mitigation in vitro. In particular, the biomass obtained for bacteria coated rice seedlings were corroborated with the performance of isolates exhibiting maximum average indole acetic acid (IAA) production respective to the agro-climatic zone. Surprisingly based on 16S rRNA, much of the propitious isolates belonged to same specific epithet exhibited variedly in their characteristics. Overall, Bacillus spp. was explored as dominant genera in toto with highest distribution in Western Plain zone followed by Central zone. Therefore, this study provides a counter-intuitive perspective of selection of native microflora for their multifarious PGP and abiotic stress tolerance abilities based on the agro-climatic zones to empower the establishment and development of more suitable inoculants for their application in agriculture under local stress environments. Copyright © 2017 Elsevier GmbH. All rights reserved.

OpenARC: Extensible OpenACC Compiler Framework for Directive-Based Accelerator Programming Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Seyong; Vetter, Jeffrey S

2014-01-01

Directive-based, accelerator programming models such as OpenACC have arisen as an alternative solution to program emerging Scalable Heterogeneous Computing (SHC) platforms. However, the increased complexity in the SHC systems incurs several challenges in terms of portability and productivity. This paper presents an open-sourced OpenACC compiler, called OpenARC, which serves as an extensible research framework to address those issues in the directive-based accelerator programming. This paper explains important design strategies and key compiler transformation techniques needed to implement the reference OpenACC compiler. Moreover, this paper demonstrates the efficacy of OpenARC as a research framework for directive-based programming study, by proposing andmore » implementing OpenACC extensions in the OpenARC framework to 1) support hybrid programming of the unified memory and separate memory and 2) exploit architecture-specific features in an abstract manner. Porting thirteen standard OpenACC programs and three extended OpenACC programs to CUDA GPUs shows that OpenARC performs similarly to a commercial OpenACC compiler, while it serves as a high-level research framework.« less

Skeletal muscle ACC2 S212 phosphorylation is not required for the control of fatty acid oxidation during exercise.

PubMed

O'Neill, Hayley M; Lally, James S; Galic, Sandra; Pulinilkunnil, Thomas; Ford, Rebecca J; Dyck, Jason R B; van Denderen, Bryce J; Kemp, Bruce E; Steinberg, Gregory R

2015-07-01

During submaximal exercise fatty acids are a predominant energy source for muscle contractions. An important regulator of fatty acid oxidation is acetyl-CoA carboxylase (ACC), which exists as two isoforms (ACC1 and ACC2) with ACC2 predominating in skeletal muscle. Both ACC isoforms regulate malonyl-CoA production, an allosteric inhibitor of carnitine palmitoyltransferase 1 (CPT-1); the primary enzyme controlling fatty acyl-CoA flux into mitochondria for oxidation. AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that is activated during exercise or by pharmacological agents such as metformin and AICAR. In resting muscle the activation of AMPK with AICAR leads to increased phosphorylation of ACC (S79 on ACC1 and S221 on ACC2), which reduces ACC activity and malonyl-CoA; effects associated with increased fatty acid oxidation. However, whether this pathway is vital for regulating skeletal muscle fatty acid oxidation during conditions of increased metabolic flux such as exercise/muscle contractions remains unknown. To examine this we characterized mice lacking AMPK phosphorylation sites on ACC2 (S212 in mice/S221 in humans-ACC2-knock-in [ACC2-KI]) or both ACC1 (S79) and ACC2 (S212) (ACC double knock-in [ACCD-KI]) during submaximal treadmill exercise and/or ex vivo muscle contractions. We find that surprisingly, ACC2-KI mice had normal exercise capacity and whole-body fatty acid oxidation during treadmill running despite elevated muscle ACC2 activity and malonyl-CoA. Similar results were observed in ACCD-KI mice. Fatty acid oxidation was also maintained in muscles from ACC2-KI mice contracted ex vivo. These findings indicate that pathways independent of ACC phosphorylation are important for regulating skeletal muscle fatty acid oxidation during exercise/muscle contractions. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Reward salience and risk aversion underlie differential ACC activity in substance dependence

PubMed Central

Alexander, William H.; Fukunaga, Rena; Finn, Peter; Brown, Joshua W.

2015-01-01

The medial prefrontal cortex, especially the dorsal anterior cingulate cortex (ACC), has long been implicated in cognitive control and error processing. Although the association between ACC and behavior has been established, it is less clear how ACC contributes to dysfunctional behavior such as substance dependence. Evidence from neuroimaging studies investigating ACC function in substance users is mixed, with some studies showing disengagement of ACC in substance dependent individuals (SDs), while others show increased ACC activity related to substance use. In this study, we investigate ACC function in SDs and healthy individuals performing a change signal task for monetary rewards. Using a priori predictions derived from a recent computational model of ACC, we find that ACC activity differs between SDs and controls in factors related to reward salience and risk aversion between SDs and healthy individuals. Quantitative fits of a computational model to fMRI data reveal significant differences in best fit parameters for reward salience and risk preferences. Specifically, the ACC in SDs shows greater risk aversion, defined as concavity in the utility function, and greater attention to rewards relative to reward omission. Furthermore, across participants risk aversion and reward salience are positively correlated. The results clarify the role that ACC plays in both the reduced sensitivity to omitted rewards and greater reward valuation in SDs. Clinical implications of applying computational modeling in psychiatry are also discussed. PMID:26106528

Reward salience and risk aversion underlie differential ACC activity in substance dependence.

PubMed

Alexander, William H; Fukunaga, Rena; Finn, Peter; Brown, Joshua W

2015-01-01

The medial prefrontal cortex, especially the dorsal anterior cingulate cortex (ACC), has long been implicated in cognitive control and error processing. Although the association between ACC and behavior has been established, it is less clear how ACC contributes to dysfunctional behavior such as substance dependence. Evidence from neuroimaging studies investigating ACC function in substance users is mixed, with some studies showing disengagement of ACC in substance dependent individuals (SDs), while others show increased ACC activity related to substance use. In this study, we investigate ACC function in SDs and healthy individuals performing a change signal task for monetary rewards. Using a priori predictions derived from a recent computational model of ACC, we find that ACC activity differs between SDs and controls in factors related to reward salience and risk aversion between SDs and healthy individuals. Quantitative fits of a computational model to fMRI data reveal significant differences in best fit parameters for reward salience and risk preferences. Specifically, the ACC in SDs shows greater risk aversion, defined as concavity in the utility function, and greater attention to rewards relative to reward omission. Furthermore, across participants risk aversion and reward salience are positively correlated. The results clarify the role that ACC plays in both the reduced sensitivity to omitted rewards and greater reward valuation in SDs. Clinical implications of applying computational modeling in psychiatry are also discussed.

Development of a Cloud Resolving Model for Heterogeneous Supercomputers

NASA Astrophysics Data System (ADS)

Sreepathi, S.; Norman, M. R.; Pal, A.; Hannah, W.; Ponder, C.

2017-12-01

A cloud resolving climate model is needed to reduce major systematic errors in climate simulations due to structural uncertainty in numerical treatments of convection - such as convective storm systems. This research describes the porting effort to enable SAM (System for Atmosphere Modeling) cloud resolving model on heterogeneous supercomputers using GPUs (Graphical Processing Units). We have isolated a standalone configuration of SAM that is targeted to be integrated into the DOE ACME (Accelerated Climate Modeling for Energy) Earth System model. We have identified key computational kernels from the model and offloaded them to a GPU using the OpenACC programming model. Furthermore, we are investigating various optimization strategies intended to enhance GPU utilization including loop fusion/fission, coalesced data access and loop refactoring to a higher abstraction level. We will present early performance results, lessons learned as well as optimization strategies. The computational platform used in this study is the Summitdev system, an early testbed that is one generation removed from Summit, the next leadership class supercomputer at Oak Ridge National Laboratory. The system contains 54 nodes wherein each node has 2 IBM POWER8 CPUs and 4 NVIDIA Tesla P100 GPUs. This work is part of a larger project, ACME-MMF component of the U.S. Department of Energy(DOE) Exascale Computing Project. The ACME-MMF approach addresses structural uncertainty in cloud processes by replacing traditional parameterizations with cloud resolving "superparameterization" within each grid cell of global climate model. Super-parameterization dramatically increases arithmetic intensity, making the MMF approach an ideal strategy to achieve good performance on emerging exascale computing architectures. The goal of the project is to integrate superparameterization into ACME, and explore its full potential to scientifically and computationally advance climate simulation and prediction.

Acetyl-CoA Carboxylase Inhibition Reverses NAFLD and Hepatic Insulin Resistance but Promotes Hypertriglyceridemia in Rodents.

PubMed

Goedeke, Leigh; Bates, Jamie; Vatner, Daniel F; Perry, Rachel J; Wang, Ting; Ramirez, Ricardo; Li, Li; Ellis, Matthew W; Zhang, Dongyan; Wong, Kari E; Beysen, Carine; Cline, Gary W; Ray, Adrian S; Shulman, Gerald I

2018-05-23

Pharmacologic inhibition of acetyl-CoA carboxylase (ACC) enzymes, ACC1 and ACC2, offers an attractive therapeutic strategy for non-alcoholic fatty liver disease (NAFLD) via simultaneous inhibition of fatty acid synthesis and stimulation of fatty acid oxidation. However, the effects of ACC inhibition on hepatic mitochondrial oxidation, anaplerosis, and ketogenesis in vivo are unknown. Here, we evaluated the impact of a novel liver-directed allosteric inhibitor of ACC1 and ACC2 (Compound 1) on these parameters, as well as glucose and lipid metabolism, in control and diet-induced rodent models of NAFLD. Oral administration of Compound 1 preferentially inhibited ACC enzymatic activity in the liver, reduced hepatic malonyl-CoA levels and enhanced hepatic ketogenesis by 50%. Furthermore, administration for 6 days to high-fructose fed rats resulted in a 20% reduction in hepatic de novo lipogenesis. Importantly, long-term treatment (21 days) significantly reduced high-fat sucrose diet (HFSD)-induced hepatic steatosis, PKCε activation and hepatic insulin resistance. ACCi treatment was associated with a significant increase in plasma triglycerides (∼30 to 130%, depending on length of fasting). ACCi-mediated hypertriglyceridemia could be attributed to a ∼15% increase in hepatic VLDL production and ∼20% reduction in triglyceride clearance by lipoprotein lipase (LPL) (P ≤ 0.05). At the molecular level, these changes were associated with increases in LXR/SREBP1 and decreases in PPARα target activation and could be reversed with fenofibrate co-treatment in a high-fat diet mouse model. Collectively, these studies warrant further investigation into the therapeutic utility of liver-directed ACC inhibition for the treatment of NAFLD and hepatic insulin resistance. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Understanding Portability of a High-Level Programming Model on Contemporary Heterogeneous Architectures

DOE PAGES

Sabne, Amit J.; Sakdhnagool, Putt; Lee, Seyong; ...

2015-07-13

Accelerator-based heterogeneous computing is gaining momentum in the high-performance computing arena. However, the increased complexity of heterogeneous architectures demands more generic, high-level programming models. OpenACC is one such attempt to tackle this problem. Although the abstraction provided by OpenACC offers productivity, it raises questions concerning both functional and performance portability. In this article, the authors propose HeteroIR, a high-level, architecture-independent intermediate representation, to map high-level programming models, such as OpenACC, to heterogeneous architectures. They present a compiler approach that translates OpenACC programs into HeteroIR and accelerator kernels to obtain OpenACC functional portability. They then evaluate the performance portability obtained bymore » OpenACC with their approach on 12 OpenACC programs on Nvidia CUDA, AMD GCN, and Intel Xeon Phi architectures. They study the effects of various compiler optimizations and OpenACC program settings on these architectures to provide insights into the achieved performance portability.« less

The Role of Ocean Eddies in the Southern Ocean Response to Observed Greenhouse Gas Forcing

NASA Astrophysics Data System (ADS)

Bilgen, S. I.; Kirtman, B. P.

2017-12-01

The Southern Ocean (SO) is crucial to understanding the possible future response to a changing climate. This is a principal region where energy is conveyed to the ocean by the westerly winds and it is here that mesoscale ocean eddies field dominate meridional heat and momentum transport. Compared to the Arctic, the Antarctic and the surrounding SO have a "delayed warming" anthropogenic greenhouse gas (GHG) response. Understanding the role of the ocean dynamics in modulating the mesoscale atmosphere-ocean interactions in the SO in a fully coupled regime is crucial to efforts aimed at predicting the consequences of the warming and variability to the climate system. The response of model run at multiple resolutions (eddy permitting, eddy resolving) to both GHG forcing and historical forcing are examined in NCAR CCSM4 with four experiments. The first simulation, 0.5° atmosphere coupled to ocean and sea ice components with 1° resolution (LR). The second simulation uses the identical atmospheric model but coupled to 0.1° ocean and sea ice component models (HR). For the third and fourth experiments, the global ocean is simulated for LR an HR models, and a climate change scenario are produced by applying a fixed (present-day) CO2 concentration. The analysis focuses on the last 55 years of two individual 155 year simulations. We discuss results from a set of state-of-art model experiments in comparison with observational estimates and explore mechanisms by examining sea surface temperature, westerly winds, surface heat flux, ocean heat transport. In LR simulations, the patterns and mechanisms of SO changes under GHG forcing are similar to those over the historical period: warming is damped southward of the ACC and enhanced to the north, however major changes between the HR simulations are explored. We find that in recent decades the Southern Annual Mode has shown a distinct upward trend, the result of an anthropogenic global warming. Also, HR simulations show that strengthening of the SAM and associated surface wind stress have been invoked to posit enhancement in the strength of the upwelling of the MOC, and increases eddy activity of the ACC. The results also indicate that eddy-permitting models are not able to capture the eddy-driven SST response since ocean dynamics is playing crucial role in the HR simulation but not in the LR models.

Lattice QCD simulations using the OpenACC platform

NASA Astrophysics Data System (ADS)

Majumdar, Pushan

2016-10-01

In this article we will explore the OpenACC platform for programming Graphics Processing Units (GPUs). The OpenACC platform offers a directive based programming model for GPUs which avoids the detailed data flow control and memory management necessary in a CUDA programming environment. In the OpenACC model, programs can be written in high level languages with OpenMP like directives. We present some examples of QCD simulation codes using OpenACC and discuss their performance on the Fermi and Kepler GPUs.

Modeling of Amorphous Calcium Carbonate

NASA Astrophysics Data System (ADS)

Sinha, Sourabh; Rez, Peter

2011-10-01

Many species (e.g. sea urchin) form amorphous calcium carbonate (ACC) precursor phases that subsequently transform into crystalline CaCO3. It is certainly possible that ACC might have up to 10 wt% Mg and ˜3 wt% of water. The structure of ACC and mechanisms by which it transforms to crystalline phase are still unknown. Our goal here is to determine an atomic structure model that is consistent with diffraction and IR measurements of ACC. For this purpose a calcite supercell with 24 formula units (120 atoms) was constructed. Various configurations with 6 Mg atoms substituting for Ca (6 wt%) and 3-5 H2O molecules (2.25- 3.75 wt%) inserted in the spaces between Ca atoms, were relaxed using VASP. Most noticeable effects were the tilts of CO3 groups and distortion of Ca sub-lattice, especially in the case of water. The distributions of nearest Ca-Ca distance and CO3 tilts were extracted from those configurations. We also performed the same analysis starting with aragonite. Sampling from above distributions we built models for amorphous calcite/aragonite of size ˜1700 nm^3. We found that the induced distortions were not enough to generate a diffraction pattern typical of an amorphous material. Next we studied diffraction pattern of several nano-crystallites as recent studies suggest that amorphous calcite might be composed of nano- crystallites. We could then generate a diffraction pattern that appeared similar to that from ACC, for a nano-crystallite of size ˜2 nm^3.

Oxygen control of ethylene biosynthesis during seed development in Arabidopsis thaliana (L.) Heynh

NASA Technical Reports Server (NTRS)

Ramonell, K. M.; McClure, G.; Musgrave, M. E.

2002-01-01

An unforeseen side-effect on plant growth in reduced oxygen is the loss of seed production at concentrations around 25% atmospheric (50 mmol mol-1 O2). In this study, the model plant Arabidopsis thaliana (L.) Heynh. cv. 'Columbia' was used to investigate the effect of low oxygen on ethylene biosynthesis during seed development. Plants were grown in a range of oxygen concentrations (210 [equal to ambient], 160, 100, 50 and 25 mmol mol-1) with 0.35 mmol mol-1 CO2 in N2. Ethylene in full-sized siliques was sampled using gas chromatography, and viable seed production was determined at maturity. Molecular analysis of ethylene biosynthesis was accomplished using cDNAs encoding 1-aminocyclopropane-1-carboxylic acid (ACC) synthase and ACC oxidase in ribonuclease protection assays and in situ hybridizations. No ethylene was detected in siliques from plants grown at 50 and 25 mmol mol-1 O2. At the same time, silique ACC oxidase mRNA increased three-fold comparing plants grown under the lowest oxygen with ambient controls, whereas ACC synthase mRNA was unaffected. As O2 decreased, tissue-specific patterning of ACC oxidase and ACC synthase gene expression shifted from the embryo to the silique wall. These data demonstrate how low O2 modulates the activity and expression of the ethylene biosynthetic pathway during seed development in Arabidopsis.

Three 1-Aminocyclopropane-1-Carboxylate Synthase Genes Regulated by Primary and Secondary Pollination Signals in Orchid Flowers1

PubMed Central

Bui, Anhthu Q.; Neill, Sharman D. O'

1998-01-01

The temporal and spatial expression patterns of three 1-aminocyclopropane-1-carboxylate (ACC) synthase genes were investigated in pollinated orchid (Phalaenopsis spp.) flowers. Pollination signals initiate a cascade of development events in multiple floral organs, including the induction of ethylene biosynthesis, which coordinates several postpollination developmental responses. The initiation and propagation of ethylene biosynthesis is regulated by the coordinated expression of three distinct ACC synthase genes in orchid flowers. One ACC synthase gene (Phal-ACS1) is regulated by ethylene and participates in amplification and interorgan transmission of the pollination signal, as we have previously described in a related orchid genus. Two additional ACC synthase genes (Phal-ACS2 and Phal-ACS3) are expressed primarily in the stigma and ovary of pollinated orchid flowers. Phal-ACS2 mRNA accumulated in the stigma within 1 h after pollination, whereas Phal-ACS1 mRNA was not detected until 6 h after pollination. Similar to the expression of Phal-ACS2, the Phal-ACS3 gene was expressed within 2 h after pollination in the ovary. Exogenous application of auxin, but not ACC, mimicked pollination by stimulating a rapid increase in ACC synthase activity in the stigma and ovary and inducing Phal-ACS2 and Phal-ACS3 mRNA accumulation in the stigma and ovary, respectively. These results provide the basis for an expanded model of interorgan regulation of three ACC synthase genes that respond to both primary (Phal-ACS2 and Phal-ACS3) and secondary (Phal-ACS1) pollination signals. PMID:9449850

A Computational Model of Major Depression: the Role of Glutamate Dysfunction on Cingulo-Frontal Network Dynamics

PubMed Central

Ramirez-Mahaluf, Juan P.; Roxin, Alexander; Mayberg, Helen S.; Compte, Albert

2017-01-01

Abstract Major depression disease (MDD) is associated with the dysfunction of multinode brain networks. However, converging evidence implicates the reciprocal interaction between midline limbic regions (typified by the ventral anterior cingulate cortex, vACC) and the dorso-lateral prefrontal cortex (dlPFC), reflecting interactions between emotions and cognition. Furthermore, growing evidence suggests a role for abnormal glutamate metabolism in the vACC, while serotonergic treatments (selective serotonin reuptake inhibitor, SSRI) effective for many patients implicate the serotonin system. Currently, no mechanistic framework describes how network dynamics, glutamate, and serotonin interact to explain MDD symptoms and treatments. Here, we built a biophysical computational model of 2 areas (vACC and dlPFC) that can switch between emotional and cognitive processing. MDD networks were simulated by slowing glutamate decay in vACC and demonstrated sustained vACC activation. This hyperactivity was not suppressed by concurrent dlPFC activation and interfered with expected dlPFC responses to cognitive signals, mimicking cognitive dysfunction seen in MDD. Simulation of clinical treatments (SSRI or deep brain stimulation) counteracted this aberrant vACC activity. Theta and beta/gamma oscillations correlated with network function, representing markers of switch-like operation in the network. The model shows how glutamate dysregulation can cause aberrant brain dynamics, respond to treatments, and be reflected in EEG rhythms as biomarkers of MDD. PMID:26514163

Identification of a copper(I) intermediate in the conversion of 1-aminocyclopropane carboxylic acid (ACC) into ethylene by Cu(II)-ACC complexes and hydrogen peroxide.

PubMed

Ghattas, Wadih; Giorgi, Michel; Mekmouche, Yasmina; Tanaka, Tsunehiro; Rockenbauer, Antal; Réglier, Marius; Hitomi, Yutaka; Simaan, A Jalila

2008-06-02

Several Cu(II) complexes with ACC (=1-aminocyclopropane carboxylic acid) or AIB (=aminoisobutyric acid) were prepared using 2,2'-bipyridine, 1,10-phenanthroline, and 2-picolylamine ligands: [Cu(2,2'-bipyridine)(ACC)(H2O)](ClO4) (1a), [Cu(1,10-phenanthroline)(ACC)](ClO4) (2a), [Cu(2-picolylamine)(ACC)](ClO4) (3a), and [Cu(2,2'-bipyridine)(AIB)(H2O)](ClO4) (1b). All of the complexes were characterized by X-ray diffraction analysis. The Cu(II)-ACC complexes are able to convert the bound ACC moiety into ethylene in the presence of hydrogen peroxide, in an "ACC-oxidase-like" activity. A few equivalents of base are necessary to deprotonate H2O2 for optimum activity. The presence of dioxygen lowers the yield of ACC conversion into ethylene by the copper(II) complexes. During the course of the reaction of Cu(II)-ACC complexes with H2O2, brown species (EPR silent and lambda max approximately 435 nm) were detected and characterized as being the Cu(I)-ACC complexes that are obtained upon reduction of the corresponding Cu(II) complexes by the deprotonated form of hydrogen peroxide. The geometry of the Cu(I) species was optimized by DFT calculations that reveal a change from square-planar to tetrahedral geometry upon reduction of the copper ion, in accordance with the observed nonreversibility of the redox process. In situ prepared Cu(I)-ACC complexes were also reacted with hydrogen peroxide, and a high level of ethylene formation was obtained. We propose Cu(I)-OOH as a possible active species for the conversion of ACC into ethylene, the structure of which was examined by DFT calculation.

Applicability of the 2013 ACC/AHA Risk Assessment and Cholesterol Treatment Guidelines in the real world: results from a multiethnic case-control study.

PubMed

Magnoni, Marco; Berteotti, Martina; Norata, Giuseppe Danilo; Limite, Luca Rosario; Peretto, Giovanni; Cristell, Nicole; Maseri, Attilio; Cianflone, Domenico

2016-01-01

The 2013 ACC/AHA cholesterol treatment guidelines have introduced a new cardiovascular risk assessment approach (PCE) and have revisited the threshold for prescribing statins. This study aims to compare the ex ante application of the ACC/AHA and the ATP-III guideline models by using a multiethnic case-control study. ATP-III-FRS and PCE were assessed in 739 patients with first STEMI and 739 age- and gender-matched controls; the proportion of cases and controls that would have been eligible for statin as primary prevention therapy and the discriminatory ability of both models were evaluated. The application of the ACC/AHA compared to the ATP-III model, resulted in an increase in sensitivity [94% (95%CI: 91%-95%) vs. 65% (61%-68%), p< 0.0001], a reduction in specificity [19% (15%-22%) vs. 55% (51%-59%), p< 0.0001] with similar global accuracy [0.56 (0.53-0.59) vs.0.59 (0.57-0.63), p ns]. When stratifying for ethnicity, the accuracy of the ACC/AHA model was higher in Europeans than in Chinese (p = 0.003) and to identified premature STEMI patients within Europeans much better compared to the ATP-III model (p = 0.0289). The application of the ACC/AHA model resulted in a significant reduction of first STEMI patients who would have escaped from preventive treatment. Age and ethnicity affected the accuracy of the ACC/AHA model improving the identification of premature STEMI among Europeans only. Key messages According to the ATP-III guideline model, about one-third of patients with STEMI would not be eligible for primary preventive treatment before STEMI. The application of the new ACC/AHA cholesterol treatment guideline model leads to a significant reduction of the percentage of patients with STEMI who would have been considered at lower risk before the STEMI. The global accuracy of the new ACC/AHA model is higher in the Europeans than in the Chinese and, moreover, among the Europeans, the application of the new ACC/AHA guideline model also improved identification of premature STEMI patients.

Fast Acceleration of 2D Wave Propagation Simulations Using Modern Computational Accelerators

PubMed Central

Wang, Wei; Xu, Lifan; Cavazos, John; Huang, Howie H.; Kay, Matthew

2014-01-01

Recent developments in modern computational accelerators like Graphics Processing Units (GPUs) and coprocessors provide great opportunities for making scientific applications run faster than ever before. However, efficient parallelization of scientific code using new programming tools like CUDA requires a high level of expertise that is not available to many scientists. This, plus the fact that parallelized code is usually not portable to different architectures, creates major challenges for exploiting the full capabilities of modern computational accelerators. In this work, we sought to overcome these challenges by studying how to achieve both automated parallelization using OpenACC and enhanced portability using OpenCL. We applied our parallelization schemes using GPUs as well as Intel Many Integrated Core (MIC) coprocessor to reduce the run time of wave propagation simulations. We used a well-established 2D cardiac action potential model as a specific case-study. To the best of our knowledge, we are the first to study auto-parallelization of 2D cardiac wave propagation simulations using OpenACC. Our results identify several approaches that provide substantial speedups. The OpenACC-generated GPU code achieved more than speedup above the sequential implementation and required the addition of only a few OpenACC pragmas to the code. An OpenCL implementation provided speedups on GPUs of at least faster than the sequential implementation and faster than a parallelized OpenMP implementation. An implementation of OpenMP on Intel MIC coprocessor provided speedups of with only a few code changes to the sequential implementation. We highlight that OpenACC provides an automatic, efficient, and portable approach to achieve parallelization of 2D cardiac wave simulations on GPUs. Our approach of using OpenACC, OpenCL, and OpenMP to parallelize this particular model on modern computational accelerators should be applicable to other computational models of wave propagation in multi-dimensional media. PMID:24497950

CFD study on the effects of boundary conditions on air flow through an air-cooled condenser

NASA Astrophysics Data System (ADS)

Sumara, Zdeněk; Šochman, Michal

2018-06-01

This study focuses on the effects of boundary conditions on effectiveness of an air-cooled condenser (ACC). Heat duty of ACC is very often calculated for ideal uniform velocity field which does not correspond to reality. Therefore, this study studies the effect of wind and different landscapes on air flow through ACC. For this study software OpenFOAM was used and the flow was simulated with the use of RANS equations. For verification of numerical setup a model of one ACC cell with dimensions of platform 1.5×1.5 [m] was used. In this experiment static pressures behind fan and air flows through a model of surface of condenser for different rpm of fan were measured. In OpenFOAM software a virtual clone of this experiment was built and different meshes, turbulent models and numerical schemes were tested. After tuning up numerical setup virtual model of real ACC system was built. Influence of wind, landscape and height of ACC on air flow through ACC has been investigated.

A modified acceleration-based monthly gravity field solution from GRACE data

NASA Astrophysics Data System (ADS)

Chen, Qiujie; Shen, Yunzhong; Chen, Wu; Zhang, Xingfu; Hsu, Houze; Ju, Xiaolei

2015-08-01

This paper describes an alternative acceleration approach for determining GRACE monthly gravity field models. The main differences compared to the traditional acceleration approach can be summarized as: (1) The position errors of GRACE orbits in the functional model are taken into account; (2) The range ambiguity is eliminated via the difference of the range measurements and (3) The mean acceleration equation is formed based on Cowell integration. Using this developed approach, a new time-series of GRACE monthly solution spanning the period January 2003 to December 2010, called Tongji_Acc RL01, has been derived. The annual signals from the Tongji_Acc RL01 time-series agree well with those from the GLDAS model. The performance of Tongji_Acc RL01 shows that this new model is comparable with the RL05 models released by CSR and JPL as well as with the RL05a model released by GFZ.

The Aristotle Comprehensive Complexity score predicts mortality and morbidity after congenital heart surgery.

PubMed

Bojan, Mirela; Gerelli, Sébastien; Gioanni, Simone; Pouard, Philippe; Vouhé, Pascal

2011-04-01

The Aristotle Comprehensive Complexity (ACC) score has been proposed for complexity adjustment in the analysis of outcome after congenital heart surgery. The score is the sum of the Aristotle Basic Complexity score, largely used but poorly related to mortality and morbidity, and of the Comprehensive Complexity items accounting for comorbidities and procedure-specific and anatomic variability. This study aims to demonstrate the ability of the ACC score to predict 30-day mortality and morbidity assessed by the length of the intensive care unit (ICU) stay. We retrospectively enrolled patients undergoing congenital heart surgery in our institution. We modeled the ACC score as a continuous variable, mortality as a binary variable, and length of ICU stay as a censored variable. For each mortality and morbidity model we performed internal validation by bootstrapping and assessed overall performance by R(2), calibration by the calibration slope, and discrimination by the c index. Among all 1,454 patients enrolled, 30-day mortality rate was 3.4% and median length of ICU stay was 3 days. The ACC score strongly related to mortality, but related to length of ICU stay only during the first postoperative week. For the mortality model, R(2) = 0.24, calibration slope = 0.98, c index = 0.86, and 95% confidence interval was 0.82 to 0.91. For the morbidity model, R(2) = 0.094, calibration slope = 0.94, c index = 0.64, and 95% confidence interval was 0.62 to 0.66. The ACC score predicts 30-day mortality and length of ICU stay during the first postoperative week. The score is an adequate tool for complexity adjustment in the analysis of outcome after congenital heart surgery. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Tone-Evoked Acoustic Change Complex (ACC) Recorded in a Sedated Animal Model.

PubMed

Presacco, Alessandro; Middlebrooks, John C

2018-05-10

The acoustic change complex (ACC) is a scalp-recorded cortical evoked potential complex generated in response to changes (e.g., frequency, amplitude) in an auditory stimulus. The ACC has been well studied in humans, but to our knowledge, no animal model has been evaluated. In particular, it was not known whether the ACC could be recorded under the conditions of sedation that likely would be necessary for recordings from animals. For that reason, we tested the feasibility of recording ACC from sedated cats in response to changes of frequency and amplitude of pure-tone stimuli. Cats were sedated with ketamine and acepromazine, and subdermal needle electrodes were used to record electroencephalographic (EEG) activity. Tones were presented from a small loudspeaker located near the right ear. Continuous tones alternated at 500-ms intervals between two frequencies or two levels. Neurometric functions were created by recording neural response amplitudes while systematically varying the magnitude of steps in frequency centered in octave frequency around 2, 4, 8, and 16 kHz, all at 75 dB SPL, or in decibel level around 75 dB SPL tested at 4 and 8 kHz. The ACC could be recorded readily under this ketamine/azepromazine sedation. In contrast, ACC could not be recorded reliably under any level of isoflurane anesthesia that was tested. The minimum frequency (expressed as Weber fractions (df/f)) or level steps (expressed in dB) needed to elicit ACC fell in the range of previous thresholds reported in animal psychophysical tests of discrimination. The success in recording ACC in sedated animals suggests that the ACC will be a useful tool for evaluation of other aspects of auditory acuity in normal hearing and, presumably, in electrical cochlear stimulation, especially for novel stimulation modes that are not yet feasible in humans.

Indian-Southern Ocean Latitudinal Transect (ISOLAT): A proposal for the recovery of high-resolution sedimentary records in the western Indian Ocean sector of the Southern Ocean

NASA Astrophysics Data System (ADS)

Mackensen, A.; Zahn, R.; Hall, I.; Kuhn, G.; Koc, N.; Francois, R.; Hemming, S.; Goldstein, S.; Rogers, J.; Ehrmann, W.

2003-04-01

Quantifying oceanic variability at timescales of oceanic, atmospheric, and cryospheric processes are the fundamental objectives of the international IMAGES program. In this context the Southern Ocean plays a leading role in that it is involved, through its influence on global ocean circulation and carbon budget, with the development and maintenance of the Earth's climate system. The seas surrounding Antarctica contain the world's only zonal circum-global current system that entrains water masses from the three main ocean basins, and maintains the thermal isolation of Antarctica from warmer surface waters to the north. Furthermore, the Southern Ocean is a major site of bottom and intermediate water formation and thus actively impacts the global thermohaline circulation (THC). This proposal is an outcome of the IMAGES Southern Ocean Working Group and constitutes one component of a suite of new IMAGES/IODP initiatives that aim at resolving past variability of the Antarctic Circumpolar Current (ACC) on orbital and sub-orbital timescales and its involvement with rapid global ocean variability and climate instability. The primary aim of this proposal is to determine millennial- to sub-centennial scale variability of the ACC and the ensuing Atlantic-Indian water transports, including surface transports and deep-water flow. We will focus on periods of rapid ocean and climate change and assess the role of the Southern Ocean in these changes, both in terms of its thermohaline circulation and biogeochemical inventories. We propose a suite of 11 sites that form a latitudinal transect across the ACC in the westernmost Indian Ocean sector of the Southern Ocean. The transect is designed to allow the reconstruction of ACC variability across a range of latitudes in conjunction with meridional shifts of the surface ocean fronts. The northernmost reaches of the transect extend into the Agulhas Current and its retroflection system which is a key component of the THC warm water return flow to the Atlantic. The principal topics are: (i) the response of the ACC to climate variability; (ii) the history of the Southern Ocean surface ocean fronts during periods of rapid climate change; (iii) the history of North Atlantic Deep Water (NADW) export to the deep South Indian Ocean; (iv) the variability of Southern Ocean biogeochemical fluxes and their influence on Circumpolar Deep Water (CDW) carbon inventories and atmospheric chemistry; and (v) the variability of surface ocean fronts and the Indian-Atlantic surface ocean density flux. To achieve these objectives we will generate fine-scale records of palaeoceanographic proxies that are linked to a variety of climatically relevant ocean parameters. Temporal resolution of the records, depending on sedimentation rates, will range from millennial to sub-centennial time scales. Highest sedimentation rates are expected at coring sites located on current-controlled sediment drifts, whereas dense sampling of cores with moderate sedimentation rates will enable at least millennial-scale events to be resolved.

[A novel gene (Aa-accA ) encoding acetyl-CoA carboxyltransferase alpha-subunit of Alkalimonas amylolytica N10 enhances salt and alkali tolerance of Escherichia coli and tobacco BY-2 cells].

PubMed

Xian, Mingjie; Zhai, Lei; Zhong, Naiqin; Ma, Yiwei; Xue, Yanfen; Ma, Yanhe

2013-08-04

Acetyl-CoA carboxylase (ACC) catalyzes the first step of fatty acid synthesis. In most bacteria, ACC is composed of four subunits encoded by accA, accB, accC, and accD. Of them, accA encodes acetyl-CoA carboxyltransferase alpha-subunit. Our prior work on proteomics of Alkalimonas amylolytica N10 showed that the expression of the Aa-accA has a remarkable response to salt and alkali stress. This research aimed to find out the Aa-accA gene contributing to salt and alkali tolerance. The Aa-accA was amplified by PCR from A. amylolytica N10 and expressed in E. coli K12 host. The effects of Aa-accA expression on the growth of transgenic strains were examined under different NaCl concentration and pH conditions. Transgenic tobacco BY-2 cells harboring Aa-accA were also generated via Agrobacterium-mediated transformation. The viability of BY-2 cells was determined with FDA staining method after salt and alkali shock. The Aa-accA gene product has 318 amino acids and is homologous to the carboxyl transferase domain of acyl-CoA carboxylases. It showed 76% identity with AccA (acetyl-CoA carboxylase carboxyltransferase subunit alpha) from E. coli. Compared to the wild-type strains, transgenic E. coli K12 strain containing Aa-accA showed remarkable growth superiority when grown in increased NaCl concentrations and pH levels. The final cell density of the transgenic strains was 2.6 and 3.5 times higher than that of the control type when they were cultivated in LB medium containing 6% (W/V) NaCl and at pH 9, respectively. Complementary expression of Aa-accA in an accA-depletion E. coli can recover the tolerance of K12 delta accA to salt and alkali stresses to some extent. Similar to the transgenic E. coli, transgenic tobacco BY-2 cells showed higher percentages of viability compared to the wild BY-2 cells under the salt or alkali stress condition. We found that Aa-accA from A. amylolytica N10 overexpression enhances the tolerance of both transgenic E. coli and tobacco BY-2 cells to NaCl and alkali stresses.

Sympathetic regulation and anterior cingulate cortex volume are altered in a rat model of chronic back pain.

PubMed

Touj, Sara; Houle, Sébastien; Ramla, Djamel; Jeffrey-Gauthier, Renaud; Hotta, Harumi; Bronchti, Gilles; Martinoli, Maria-Grazia; Piché, Mathieu

2017-06-03

Chronic pain is associated with autonomic disturbance. However, specific effects of chronic back pain on sympathetic regulation remain unknown. Chronic pain is also associated with structural changes in the anterior cingulate cortex (ACC), which may be linked to sympathetic dysregulation. The aim of this study was to determine whether sympathetic regulation and ACC surface and volume are affected in a rat model of chronic back pain, in which complete Freund Adjuvant (CFA) is injected in back muscles. Sympathetic regulation was assessed with renal blood flow (RBF) changes induced by electrical stimulation of a hind paw, while ACC structure was examined by measuring cortical surface and volume. RBF changes and ACC volume were compared between control rats and rats injected with CFA in back muscles segmental (T10) to renal sympathetic innervation or not (T2). In rats with CFA, chronic inflammation was observed in the affected muscles in addition to increased nuclear factor-kappa B (NF-kB) protein expression in corresponding spinal cord segments (p=0.01) as well as decreased ACC volume (p<0.05). In addition, intensity-dependent decreases in RBF during hind paw stimulation were attenuated by chronic pain at T2 (p's<0.05) and T10 (p's<0.05), but less so at T10 compared with T2 (p's<0.05). These results indicate that chronic back pain alters sympathetic functions through non-segmental mechanisms, possibly by altering descending regulatory pathways from ACC. Yet, segmental somato-sympathetic reflexes may compete with non-segmental processes depending on the back region affected by pain and according to the segmental organization of the sympathetic nervous system. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

VizieR Online Data Catalog: Radiative forces for stellar envelopes (Seaton, 1997)

NASA Astrophysics Data System (ADS)

Seaton, M. J.; Yan, Y.; Mihalas, D.; Pradhan, A. K.

2000-02-01

(1) Primary data files, stages.zz These files give data for the calculation of radiative accelerations, GRAD, for elements with nuclear charge zz. Data are available for zz=06, 07, 08, 10, 11, 12, 13, 14, 16, 18, 20, 24, 25, 26 and 28. Calculations are made using data from the Opacity Project (see papers SYMP and IXZ). The data are given for each ionisation stage, j. They are tabulated on a mesh of (T, Ne, CHI) where T is temperature, Ne electron density and CHI is abundance multiplier. The files include data for ionisation fractions, for each (T, Ne). The file contents are described in the paper ACC and as comments in the code add.f (2) Code add.f This reads a file stages.zz and creates a file acc.zz giving radiative accelerations averaged over ionisation stages. The code prompts for names of input and output files. The code, as provided, gives equal weights (as defined in the paper ACC) to all stages. Th weights are set in SUBROUTINE WEIGHTS, which could be changed to give any weights preferred by the user. The dependence of diffusion coefficients on ionisation stage is given by a function ZET, which is defined in SUBROUTINE ZETA. The expressions used for ZET are as given in the paper. The user can change that subroutine if other expressions are preferred. The output file contains values, ZETBAR, of ZET, averaged over ionisation stages. (3) Files acc.zz Radiative accelerations computed using add.f as provided. The user will need to run the code add.f only if it is required to change the subroutines WEIGHTS or ZETA. The contents of the files acc.zz are described in the paper ACC and in comments contained in the code add.f. (4) Code accfit.f This code gives gives radiative accelerations, and some related data, for a stellar model. Methods used to interpolate data to the values of (T, RHO) for the stellar model are based on those used in the code opfit.for (see the paper OPF). The executable file accfit.com runs accfit.f. It uses a list of files given in accfit.files (see that file for further description). The mesh used for the abundance-multiplier CHI on the output file will generally be finer than that used in the input files acc.zz. The mesh to be used is specified on a file chi.dat. For a test run, the stellar model used is given in the file 10000_4.2 (Teff=10000 K, LOG10(g)=4.2) The output file from that test run is acc100004.2. The contents of the output file are described in the paper ACC and as comments in the code accfit.f. (5) The code diff.f This code reads the output file (e.g. acc1000004.2) created by accfit.f. For any specified depth point in the model and value of CHI, it gives values of radiative accelerations, the quantity ZETBAR required for calculation of diffusion coefficients, and Rosseland-mean opacities. The code prompts for input data. It creates a file recording all data calculated. The code diff.f is intended for incorporation, as a set of subroutines, in codes for diffusion calculations. (1 data file).

Recombinant yeast screen for new inhibitors of human acetyl-CoA carboxylase 2 identifies potential drugs to treat obesity

PubMed Central

Marjanovic, Jasmina; Chalupska, Dominika; Patenode, Caroline; Coster, Adam; Arnold, Evan; Ye, Alice; Anesi, George; Lu, Ying; Okun, Ilya; Tkachenko, Sergey; Haselkorn, Robert; Gornicki, Piotr

2010-01-01

Acetyl-CoA carboxylase (ACC) is a key enzyme of fatty acid metabolism with multiple isozymes often expressed in different eukaryotic cellular compartments. ACC-made malonyl-CoA serves as a precursor for fatty acids; it also regulates fatty acid oxidation and feeding behavior in animals. ACC provides an important target for new drugs to treat human diseases. We have developed an inexpensive nonradioactive high-throughput screening system to identify new ACC inhibitors. The screen uses yeast gene-replacement strains depending for growth on cloned human ACC1 and ACC2. In “proof of concept” experiments, growth of such strains was inhibited by compounds known to target human ACCs. The screen is sensitive and robust. Medium-size chemical libraries yielded new specific inhibitors of human ACC2. The target of the best of these inhibitors was confirmed with in vitro enzymatic assays. This compound is a new drug chemotype inhibiting human ACC2 with 2.8 μM IC50 and having no effect on human ACC1 at 100 μM. PMID:20439761

NMDA and AMPA receptors in the anterior cingulate cortex mediates visceral pain in visceral hypersensitivity rats.

PubMed

Zhou, Lin; Huang, Junjing; Gao, Jun; Zhang, Guanpo; Jiang, Jinjin

2014-02-01

Several studies have shown that N-methyl-D-aspartate (NMDA)-receptor activation in anterior cingulate cortex (ACC) neurons plays critical roles in modulating visceral pain responses in visceral hypersensitivity (VH) rats. However, there are few reports about the expressions of NMDA and α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic-acid (AMPA) receptor subtypes in ACC of VH model rats at different time points. The current study was undertaken to investigate NR2A, NR2B and GluR2 expressions in ACC of VH rats that were induced by administration with 5% mustard oil. Our results indicated that NR2B, but not NR2A, was highly expressed in VH model group on day 15, 22, and 36 compared with normal group (p < 0.05). GluR2 expression was also higher in VH model group on day 15, 22, and 36 than that of normal group (p < 0.05). These findings suggested increased expression of NR2B and GluR2 might be key mechanisms for long-term synaptic plastic changes in VH rats. Copyright © 2014. Published by Elsevier Inc.

Effects of Low O2 Root Stress on Ethylene Biosynthesis in Tomato Plants (Lycopersicon esculentum Mill cv Heinz 1350) 1

PubMed Central

Wang, Tzann-Wei; Arteca, Richard N.

1992-01-01

Low O2 conditions were obtained by flowing N2 through the solution in which the tomato plants (Lycopersicon esculentum Mill cv Heinz 1350) were growing. Time course experiments revealed that low O2 treatments stimulated 1-aminocyclopropane-1-carboxylate (ACC) synthase production in the roots and leaves. After the initiation of low O2 conditions, ACC synthase activity and ACC content in the roots increased and reached a peak after 12 and 20 hours, respectively. The conversion of ACC to ethylene in the roots was inhibited by low levels of O2, and ACC was apparently transported to the leaves where it was converted to ethylene. ACC synthase activity in the leaves was also stimulated by low O2 treatment to the roots, reaching a peak after 24 hours. ACC synthase levels were enhanced by cobalt chloride and aminooxyacetic acid (AOA), although they inhibited ethylene production. Cobalt chloride enhanced ACC synthase only in combination with low O2 conditions in the roots. Under aeration, AOA stimulated ACC synthase activity in both the roots and leaves. However, in combination with low O2 conditions, AOA caused a stimulation in ACC synthase activity in the leaves and no effect in the roots. PMID:16668654

Role of an Essential Acyl Coenzyme A Carboxylase in the Primary and Secondary Metabolism of Streptomyces coelicolor A3(2)

PubMed Central

Rodríguez, E.; Banchio, C.; Diacovich, L.; Bibb, M. J.; Gramajo, H.

2001-01-01

Two genes, accB and accE, that form part of the same operon, were cloned from Streptomyces coelicolor A3(2). AccB is homologous to the carboxyl transferase domain of several propionyl coezyme A (CoA) carboxylases and acyl-CoA carboxylases (ACCases) of actinomycete origin, while AccE shows no significant homology to any known protein. Expression of accB and accE in Escherichia coli and subsequent in vitro reconstitution of enzyme activity in the presence of the biotinylated protein AccA1 or AccA2 confirmed that AccB was the carboxyl transferase subunit of an ACCase. The additional presence of AccE considerably enhanced the activity of the enzyme complex, suggesting that this small polypeptide is a functional component of the ACCase. The impossibility of obtaining an accB null mutant and the thiostrepton growth dependency of a tipAp accB conditional mutant confirmed that AccB is essential for S. coelicolor viability. Normal growth phenotype in the absence of the inducer was restored in the conditional mutant by the addition of exogenous long-chain fatty acids in the medium, indicating that the inducer-dependent phenotype was specifically related to a conditional block in fatty acid biosynthesis. Thus, AccB, together with AccA2, which is also an essential protein (E. Rodriguez and H. Gramajo, Microbiology 143:3109–3119, 1999), are the most likely components of an ACCase whose main physiological role is the synthesis of malonyl-CoA, the first committed step of fatty acid synthesis. Although normal growth of the conditional mutant was restored by fatty acids, the cultures did not produce actinorhodin or undecylprodigiosin, suggesting a direct participation of this enzyme complex in the supply of malonyl-CoA for the synthesis of these secondary metabolites. PMID:11526020

Accumulated Delivered Dose Response of Stereotactic Body Radiation Therapy for Liver Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaminath, Anand; Massey, Christine; Brierley, James D.

2015-11-01

Purpose: To determine whether the accumulated dose using image guided radiation therapy is a stronger predictor of clinical outcomes than the planned dose in stereotactic body radiation therapy (SBRT) for liver metastases. Methods and Materials: From 2003 to 2009, 81 patients with 142 metastases were treated in institutional review board–approved SBRT studies (5-10 fractions). Patients were treated during free breathing (with or without abdominal compression) or with controlled exhale breath-holding. SBRT was planned on a static exhale computed tomography (CT) scan, and the minimum planning target volume dose to 0.5 cm{sup 3} (minPTV) was recorded. The accumulated minimum dose to themore » 0.5 cm{sup 3} gross tumor volume (accGTV) was calculated after performing dose accumulation from exported image guided radiation therapy data sets registered to the planning CT using rigid (2-dimensional MV/kV orthogonal) or deformable (3-dimensional/4-dimensional cone beam CT) image registration. Univariate and multivariate Cox regression models assessed the factors influencing the time to local progression (TTLP). Hazard ratios for accGTV and minPTV were compared using model goodness-of-fit and bootstrapping. Results: Overall, the accGTV dose exceeded the minPTV dose in 98% of the lesions. For 5 to 6 fractions, accGTV doses of >45 Gy were associated with 1-year local control of 86%. On univariate analysis, the cancer subtype (breast), smaller tumor volume, and increased dose were significant predictors for improved TTLP. The dose and volume were uncorrelated; the accGTV dose and minPTV dose were correlated and were tested separately on multivariate models. Breast cancer subtype, accGTV dose (P<.001), and minPTV dose (P=.02) retained significance in the multivariate models. The univariate hazard ratio for TTLP for 5-Gy increases in accGTV versus minPTV was 0.67 versus 0.74 (all patients; 95% confidence interval of difference 0.03-0.14). Goodness-of-fit testing confirmed the accGTV dose as a stronger dose–response predictor than the minPTV dose. Conclusions: The accGTV dose is a better predictor of TTLP than the minPTV dose for liver metastasis SBRT. The use of modern image guided radiation therapy in future analyses of dose–response outcomes should increase the concordance between the planned and delivered doses.« less

Rostral anterior cingulate cortex activity and early symptom improvement during treatment for major depressive disorder

PubMed Central

Korb, Alexander S.; Hunter, Aimee M.; Cook, Ian A.; Leuchter, Andrew F.

2011-01-01

In treatment trials for Major Depressive Disorder (MDD), early symptom improvement is predictive of eventual clinical response. Clinical response may also be predicted by elevated pretreatment theta (4-7 Hz) current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC). We investigated the relationship between pretreatment EEG and early improvement in predicting clinical outcome in 72 MDD subjects across three placebo-controlled treatment trials. Subjects were randomized to receive fluoxetine, venlafaxine, or placebo. Theta current density in the rACC and mOFC was computed with Low-Resolution Brain Electromagnetic Tomography (LORETA). An ANCOVA, examining week 8 Hamilton Depression Rating Scale (HamD) percent change, showed a significant effect of week-2-HamD-percent-change, and a significant three-way interaction of week-2-HamD-percent-change × Treatment × rACC. Medication subjects with robust early improvement showed almost no relationship between rACC theta current density and final clinical outcome. However, in subjects with little early improvement, rACC activity showed a strong relationship with clinical outcome. The model examining mOFC showed a trend in the three-way interaction. A combination of pretreatment rACC activity and early symptom improvement may be useful for predicting treatment response. PMID:21546222

Mortality Risk After Transcatheter Aortic Valve Implantation: Analysis of the Predictive Accuracy of the Transcatheter Valve Therapy Registry Risk Assessment Model.

PubMed

Codner, Pablo; Malick, Waqas; Kouz, Remi; Patel, Amisha; Chen, Cheng-Han; Terre, Juan; Landes, Uri; Vahl, Torsten Peter; George, Isaac; Nazif, Tamim; Kirtane, Ajay J; Khalique, Omar K; Hahn, Rebecca T; Leon, Martin B; Kodali, Susheel

2018-05-08

Risk assessment tools currently used to predict mortality in transcatheter aortic valve implantation (TAVI) were designed for patients undergoing cardiac surgery. We aim to assess the accuracy of the TAVI dedicated American College of Cardiology / Transcatheter Valve Therapies (ACC/TVT) risk score in predicting mortality outcomes. Consecutive patients (n=1038) undergoing TAVI at a single institution from 2014 to 2016 were included. The ACC/TVT registry mortality risk score, the Society of Thoracic Surgeons - Patient Reported Outcomes (STS-PROM) score and the EuroSCORE II were calculated for all patients. In hospital and 30-day all-cause mortality rates were 1.3% and 2.9%, respectively. The ACC/TVT risk stratification tool scored higher for patients who died in-hospital than in those who survived the index hospitalization (6.4 ± 4.6 vs. 3.5 ± 1.6, p = 0.03; respectively). The ACC/TVT score showed a high level of discrimination, C-index for in-hospital mortality 0.74, 95% CI [0.59 - 0.88]. There were no significant differences between the performance of the ACC/TVT registry risk score, the EuroSCORE II and the STS-PROM for in hospital and 30-day mortality rates. The ACC/TVT registry risk model is a dedicated tool to aid in the prediction of in-hospital mortality risk after TAVI.

Genetic Profiling Reveals Cross-Contamination and Misidentification of 6 Adenoid Cystic Carcinoma Cell Lines: ACC2, ACC3, ACCM, ACCNS, ACCS and CAC2

PubMed Central

Phuchareon, Janyaporn; Ohta, Yoshihito; Woo, Jonathan M.; Eisele, David W.; Tetsu, Osamu

2009-01-01

Adenoid cystic carcinoma (ACC) is the second most common malignant neoplasm of the salivary glands. Most patients survive more than 5 years after surgery and postoperative radiation therapy. The 10 year survival rate, however, drops to 40%, due to locoregional recurrences and distant metastases. Improving long-term survival in ACC requires the development of more effective systemic therapies based on a better understanding of the biologic behavior of ACC. Much preclinical research in this field involves the use of cultured cells and, to date, several ACC cell lines have been established. Authentication of these cell lines, however, has not been reported. We performed DNA fingerprint analysis on six ACC cell lines using short tandem repeat (STR) examinations and found that all six cell lines had been contaminated with other cells. ACC2, ACC3, and ACCM were determined to be cervical cancer cells (HeLa cells), whereas the ACCS cell line was composed of T24 urinary bladder cancer cells. ACCNS and CAC2 cells were contaminated with cells derived from non-human mammalian species: the cells labeled ACCNS were mouse cells and the CAC2 cells were rat cells. These observations suggest that future studies using ACC cell lines should include cell line authentication to avoid the use of contaminated or non-human cells. PMID:19557180

An OpenACC-Based Unified Programming Model for Multi-accelerator Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Jungwon; Lee, Seyong; Vetter, Jeffrey S

2015-01-01

This paper proposes a novel SPMD programming model of OpenACC. Our model integrates the different granularities of parallelism from vector-level parallelism to node-level parallelism into a single, unified model based on OpenACC. It allows programmers to write programs for multiple accelerators using a uniform programming model whether they are in shared or distributed memory systems. We implement a prototype of our model and evaluate its performance with a GPU-based supercomputer using three benchmark applications.

Chemical and physical controls on the transformation of amorphous calcium carbonate into crystalline CaCO3 polymorphs

NASA Astrophysics Data System (ADS)

Blue, C. R.; Giuffre, A.; Mergelsberg, S.; Han, N.; De Yoreo, J. J.; Dove, P. M.

2017-01-01

Calcite and other crystalline polymorphs of CaCO3 can form by pathways involving amorphous calcium carbonate (ACC). Apparent inconsistencies in the literature indicate the relationships between ACC composition, local conditions, and the subsequent crystalline polymorphs are not yet established. This experimental study quantifies the control of solution composition on the transformation of ACC into crystalline polymorphs in the presence of magnesium. Using a mixed flow reactor to control solution chemistry, ACC was synthesized with variable Mg contents by tuning input pH, Mg/Ca, and total carbonate concentration. ACC products were allowed to transform within the output suspension under stirred or quiescent conditions while characterizing the evolving solutions and solids. As the ACC transforms into a crystalline phase, the solutions record a polymorph-specific evolution of pH and Mg/Ca. The data provide a quantitative framework for predicting the initial polymorph that forms from ACC based upon the solution aMg2+/aCa2+ and aCO32-/aCa2+ and stirring versus quiescent conditions. This model reconciles discrepancies among previous studies that report on the nature of the polymorphs produced from ACC and supports the previous claim that monohydrocalcite may be an important, but overlooked, transient phase on the way to forming some aragonite and calcite deposits. By this construct, organic additives and extreme pH are not required to tune the composition and nature of the polymorph that forms. Our measurements show that the Mg content of ACC is recorded in the resulting calcite with a ≈1:1 dependence. By correlating composition of these calcite products with the Mgtot/Catot of the initial solutions, we find a ≈3:1 dependence that is approximately linear and general to whether calcite is formed via an ACC pathway or by the classical step-propagation process. Comparisons to calcite grown in synthetic seawater show a ≈1:1 dependence. The relationships suggest that the local Mg2+/Ca2+ at the time of precipitation determines the calcite composition, independent of whether growth occurs via an amorphous intermediate or classical pathway for a range of supersaturations and pH conditions. The findings reiterate the need to revisit the traditional picture of chemical and physical controls on CaCO3 polymorph selection. Mineralization by pathways involving ACC can lead to the formation of crystalline phases whose polymorphs and compositions are out of equilibrium with local growth media. As such, classical thermodynamic equilibria may not provide a reliable predictor of observed compositions.

On the structure of amorphous calcium carbonate--a detailed study by solid-state NMR spectroscopy.

PubMed

Nebel, Holger; Neumann, Markus; Mayer, Christian; Epple, Matthias

2008-09-01

The calcium carbonate phases calcite, aragonite, vaterite, monohydrocalcite (calcium carbonate monohydrate), and ikaite (calcium carbonate hexahydrate) were studied by solid-state NMR spectroscopy ( (1)H and (13)C). Further model compounds were sodium hydrogencarbonate, potassium hydrogencarbonate, and calcium hydroxide. With the help of these data, the structure of synthetically prepared additive-free amorphous calcium carbonate (ACC) was analyzed. ACC contains molecular water (as H 2O), a small amount of mobile hydroxide, and no hydrogencarbonate. This supports the concept of ACC as a transient precursor in the formation of calcium carbonate biominerals.

Heat uptake in the Southern Ocean in a warmer, windier world: a process-based analysis using an AOGCM with an eddy-permitting ocean

NASA Astrophysics Data System (ADS)

Kuhlbrodt, T.; Gregory, J. M.

2016-02-01

About 90% of the anthropogenic increase in heat stored in the climate system is found the oceans. Therefore it is relevant to understand the details of ocean heat uptake. Here we present a detailed, process-based analysis of ocean heat uptake (OHU) processes in HiGEM1.2, an atmosphere-ocean general circulation model (AOGCM) with an eddy-permitting ocean component of 1/3° resolution. Similarly to various other models, HiGEM1.2 shows that the global heat budget is dominated by a downward advection of heat compensated by upward isopycnal diffusion. This upward isopycnal diffusion of heat is located mostly in the Southern Ocean (Fig. 1a).We compare the responses to a 4xCO2 forcing and an enhancement of the windstress forcing in the Southern Ocean. In line with the CMIP5 models, HiGEM1.2 shows a band of strong OHU in the mid-latitude Southern Ocean in the 4xCO2 run, which is mostly advective. By contrast, in the high-latitude Southern Ocean regions it is the suppression of convection that leads to OHU (Fig. 1b). In the enhanced windstress run, convection is strengthened at high Southern latitudes (Fig. 1c), leading to heat loss, while the magnitude of the OHU in the Southern mid-latitudes is very similar to the 4xCO2 results. Remarkably, there is only very small global OHU in the enhanced windstress run. The wind stress forcing just leads to a redistribution of heat. We relate the ocean changes at high southern latitudes to the effect of climate change on the Antarctic Circumpolar Current (ACC). It weakens in the 4xCO2 run and strengthens in the wind stress run. The weakening is due to a narrowing of the ACC, caused by an expansion of the Weddell Gyre, and a flattening of the isopycnals, which are explained by a combination of the wind stress forcing and increased precipitation. The presentation will also try to clarify the definitions of terms like "advective", "diffusive" and "eddy-induced" when used for observed and modelled (at various resolutions) ocean heat uptake processes. Fig. 1: Horizontally averaged temperature tendency diagnostics for the high-latitude Southern Ocean, for (a) the control run, (b) the 4xCO2 anomalies and (c) the windstress anomalies. Both axes are scaled according to a power law. "VM"- vertical mixing, which includes convection ("conv").

Minimal impact of age and housing temperature on the metabolic phenotype of Acc2-/- mice.

PubMed

Brandon, Amanda E; Stuart, Ella; Leslie, Simon J; Hoehn, Kyle L; James, David E; Kraegen, Edward W; Turner, Nigel; Cooney, Gregory J

2016-03-01

An important regulator of fatty acid oxidation (FAO) is the allosteric inhibition of CPT-1 by malonyl-CoA produced by the enzyme acetyl-CoA carboxylase 2 (ACC2). Initial studies suggested that deletion of Acc2 (Acacb) increased fat oxidation and reduced adipose tissue mass but in an independently generated strain of Acc2 knockout mice we observed increased whole-body and skeletal muscle FAO and a compensatory increase in muscle glycogen stores without changes in glucose tolerance, energy expenditure or fat mass in young mice (12-16 weeks). The aim of the present study was to determine whether there was any effect of age or housing at thermoneutrality (29 °C; which reduces total energy expenditure) on the phenotype of Acc2 knockout mice. At 42-54 weeks of age, male WT and Acc2(-/-) mice had similar body weight, fat mass, muscle triglyceride content and glucose tolerance. Consistent with younger Acc2(-/-) mice, aged Acc2(-/-) mice showed increased whole-body FAO (24 h average respiratory exchange ratio=0.95±0.02 and 0.92±0.02 for WT and Acc2(-/-) mice respectively, P<0.05) and skeletal muscle glycogen content (+60%, P<0.05) without any detectable change in whole-body energy expenditure. Hyperinsulinaemic-euglycaemic clamp studies revealed no difference in insulin action between groups with similar glucose infusion rates and tissue glucose uptake. Housing Acc2(-/-) mice at 29 °C did not alter body composition, glucose tolerance or the effects of fat feeding compared with WT mice. These results confirm that manipulation of Acc2 may alter FAO in mice, but this has little impact on body composition or insulin action. © 2016 Society for Endocrinology.

Anti-diarrhoeal investigation from aqueous extract of Cuminum cyminum Linn. Seed in Albino rats

PubMed Central

Sahoo, Himanshu Bhusan; Sahoo, Saroj Kumar; Sarangi, Sarada Prasad; Sagar, Rakesh; Kori, Mohan Lal

2014-01-01

Background: Cuminum cyminum Linn. (Umbelliferae), commonly known as Jeera. It is native from mediterranean region, but today widely cultivated in Asian countries. It has been reported to possess various medicinal properties and an important food ingredient. The seed of the plant are claimed for treatment of diarrhoea by various traditional practitioners. Objectives: Hence, the present investigation was undertaken to evaluate aq. extract of C. cyminum seeds (ACCS) against diarrhoea on albino rats. Materials and Methods: The animals were divided into five groups and the control group was applied with 2% acacia suspension, the standard group with loperamide (3 mg/kg) or atropine sulphate (5mg/kg) and three test groups administered orally with 100, 250 and 500 mg/kg of ACCS. The antidiarrhoeal effect was investigated by castor oil induce diarrhoea model, prostaglandin E2 (PGE2) induced enteropooling model, intestinal transit by charcoal meal test. Results: The ACCS showed significant (P < 0.001) inhibition in frequency of diarrhoea, defecation time delaying, secretion of intestinal fluid as well as intestinal propulsion as compared to control and the graded doses of tested extract followed dose dependent protection against diarrhoea. Conclusions: The study reveals that the ACCS is a potent antidiarrhoeal drug which supports the traditional claim. PMID:25002800

Experimental study of condensate subcooling with the use of a model of an air-cooled condenser

NASA Astrophysics Data System (ADS)

Sukhanov, V. A.; Bezukhov, A. P.; Bogov, I. A.; Dontsov, N. Y.; Volkovitsky, I. D.; Tolmachev, V. V.

2016-01-01

Water-supply deficit is now felt in many regions of the world. This hampers the construction of new steam-turbine and combined steam-and-gas thermal power plants. The use of dry cooling systems and, specifically, steam-turbine air-cooled condensers (ACCs) expands the choice of sites for the construction of such power plants. The significance of condensate subcooling Δ t as a parameter that negatively affects the engineering and economic performance of steam-turbine plants is thereby increased. The operation and design factors that influence the condensate subcooling in ACCs are revealed, and the research objective is, thus, formulated properly. The indicated research was conducted through physical modeling with the use of the Steam-Turbine Air-Cooled Condenser Unit specialized, multipurpose, laboratory bench. The design and the combined schematic and measurement diagram of this test bench are discussed. The experimental results are presented in the form of graphic dependences of the condensate subcooling value on cooling ratio m and relative weight content ɛ' of air in steam at the ACC inlet at different temperatures of cooling air t ca ' . The typical ranges of condensate subcooling variation (4 ≤ Δ t ≤ 6°C, 2 ≤ Δ t ≤ 4°C, and 0 ≤ Δ t ≤ 2°C) are identified based on the results of analysis of the attained Δ t levels in the ACC and numerous Δ t reduction estimates. The corresponding ranges of cooling ratio variation at different temperatures of cooling air at the ACC inlet are specified. The guidelines for choosing the adjusted ranges of cooling ratio variation with account of the results of experimental studies of the dependences of the absolute pressure of the steam-air mixture in the top header of the ACC and the heat flux density on the cooling ratio at different temperatures of cooling air at the ACC inlet are given.

Autologous Cartilage Chip Transplantation Improves Repair Tissue Composition Compared With Marrow Stimulation.

PubMed

Christensen, Bjørn Borsøe; Olesen, Morten Lykke; Lind, Martin; Foldager, Casper Bindzus

2017-06-01

Repair of chondral injuries by use of cartilage chips has recently demonstrated clinical feasibility. To investigate in vivo cartilage repair outcome of autologous cartilage chips compared with marrow stimulation in full-thickness cartilage defects in a minipig model. Controlled laboratory study. Six Göttingen minipigs received two 6-mm chondral defects in the medial and lateral trochlea of each knee. The two treatment groups were (1) autologous cartilage chips embedded in fibrin glue (ACC) (n = 12) and (2) marrow stimulation (MST) (n = 12). The animals were euthanized after 6 months, and the composition of repair tissue was quantitatively determined using histomorphometry. Semiquantitative evaluation was performed by means of the International Cartilage Repair Society (ICRS) II score. Collagen type II staining was used to further evaluate the repair tissue composition. Significantly more hyaline cartilage was found in the ACC (17.1%) compared with MST (2.9%) group ( P < .01). Furthermore, the ACC group had significantly less fibrous tissue (23.8%) compared with the MST group (41.1%) ( P < .01). No significant difference in fibrocartilage content was found (54.7% for ACC vs 50.8% for MST). The ACC group had significantly higher ICRS II scores for tissue morphological characteristics, matrix staining, cell morphological characteristics, surface assessment, mid/deep assessment, and overall assessment ( P < .05). The ACC-treated defects had significantly more collagen type II staining (54.5%) compared with the MST-treated defects (28.1%) ( P < .05). ACC transplant resulted in improved quality of cartilage repair tissue compared with MST at 6 months postoperatively. Further studies are needed to investigate ACC as a possible alternative first-line treatment for focal cartilage injuries in the knee.

Variation of Antarctic circumpolar current and its intensification in relation to the southern annular mode detected in the time-variable gravity signals by GRACE satellite

NASA Astrophysics Data System (ADS)

Liau, Jen-Ru; Chao, Benjamin F.

2017-07-01

The southern annular mode (SAM) in the atmosphere and the Antarctic circumpolar current (ACC) in the ocean play decisive roles in the climatic system of the mid- to high-latitude southern hemisphere. Using the time-variable gravity data from the GRACE satellite mission, we find the link between the space-time variabilities of the ACC and the SAM. We calculate the empirical orthogonal functions (EOF) of the non-seasonal ocean bottom pressure (OBP) field in the circum-Antarctic seas from the GRACE data for the period from 2003 to 2015. We find that the leading EOF mode of the non-seasonal OBP represents a unison OBP oscillation around Antarctica with time history closely in pace with that of the SAM Index with a high correlation of 0.77. This OBP variation gives rise to a variation in the geostrophic flow field; the result for the same EOF mode shows heightened variations in the zonal velocity that resides primarily in the eastern hemispheric portion of the ACC and coincided geographically with the southernmost boundary of the ACC's main stream. Confirming previous oceanographic studies, these geodetic satellite results provide independent information toward better understanding of the ACC-SAM process.

Comparison of application of the ACC/AHA guidelines, Adult Treatment Panel III guidelines, and European Society of Cardiology guidelines for cardiovascular disease prevention in a European cohort.

PubMed

Kavousi, Maryam; Leening, Maarten J G; Nanchen, David; Greenland, Philip; Graham, Ian M; Steyerberg, Ewout W; Ikram, M Arfan; Stricker, Bruno H; Hofman, Albert; Franco, Oscar H

2014-04-09

The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines introduced a prediction model and lowered the threshold for treatment with statins to a 7.5% 10-year hard atherosclerotic cardiovascular disease (ASCVD) risk. Implications of the new guideline's threshold and model have not been addressed in non-US populations or compared with previous guidelines. To determine population-wide implications of the ACC/AHA, the Adult Treatment Panel III (ATP-III), and the European Society of Cardiology (ESC) guidelines using a cohort of Dutch individuals aged 55 years or older. We included 4854 Rotterdam Study participants recruited in 1997-2001. We calculated 10-year risks for "hard" ASCVD events (including fatal and nonfatal coronary heart disease [CHD] and stroke) (ACC/AHA), hard CHD events (fatal and nonfatal myocardial infarction, CHD mortality) (ATP-III), and atherosclerotic CVD mortality (ESC). Events were assessed until January 1, 2012. Per guideline, we calculated proportions of individuals for whom statins would be recommended and determined calibration and discrimination of risk models. The mean age was 65.5 (SD, 5.2) years. Statins would be recommended for 96.4% (95% CI, 95.4%-97.1%; n = 1825) of men and 65.8% (95% CI, 63.8%-67.7%; n = 1523) of women by the ACC/AHA, 52.0% (95% CI, 49.8%-54.3%; n = 985) of men and 35.5% (95% CI, 33.5%-37.5%; n = 821) of women by the ATP-III, and 66.1% (95% CI, 64.0%-68.3%; n = 1253) of men and 39.1% (95% CI, 37.1%-41.2%; n = 906) of women by ESC guidelines. With the ACC/AHA model, average predicted risk vs observed cumulative incidence of hard ASCVD events was 21.5% (95% CI, 20.9%-22.1%) vs 12.7% (95% CI, 11.1%-14.5%) for men (192 events) and 11.6% (95% CI, 11.2%-12.0%) vs 7.9% (95% CI, 6.7%-9.2%) for women (151 events). Similar overestimation occurred with the ATP-III model (98 events in men and 62 events in women) and ESC model (50 events in men and 37 events in women). The C statistic was 0.67 (95% CI, 0.63-0.71) in men and 0.68 (95% CI, 0.64-0.73) in women for hard ASCVD (ACC/AHA), 0.67 (95% CI, 0.62-0.72) in men and 0.69 (95% CI, 0.63-0.75) in women for hard CHD (ATP-III), and 0.76 (95% CI, 0.70-0.82) in men and 0.77 (95% CI, 0.71-0.83) in women for CVD mortality (ESC). In this European population aged 55 years or older, proportions of individuals eligible for statins differed substantially among the guidelines. The ACC/AHA guideline would recommend statins for nearly all men and two-thirds of women, proportions exceeding those with the ATP-III or ESC guidelines. All 3 risk models provided poor calibration and moderate to good discrimination. Improving risk predictions and setting appropriate population-wide thresholds are necessary to facilitate better clinical decision making.

The time course of activity in dorsolateral prefrontal cortex and anterior cingulate cortex during top-down attentional control.

PubMed

Silton, Rebecca Levin; Heller, Wendy; Towers, David N; Engels, Anna S; Spielberg, Jeffrey M; Edgar, J Christopher; Sass, Sarah M; Stewart, Jennifer L; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

2010-04-15

A network of brain regions has been implicated in top-down attentional control, including left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC). The present experiment evaluated predictions of the cascade-of-control model (Banich, 2009), which predicts that during attentionally-demanding tasks, LDLPFC imposes a top-down attentional set which precedes late-stage selection performed by dACC. Furthermore, the cascade-of-control model argues that dACC must increase its activity to compensate when top-down control by LDLPFC is poor. The present study tested these hypotheses using fMRI and dense-array ERP data collected from the same 80 participants in separate sessions. fMRI results guided ERP source modeling to characterize the time course of activity in LDLPFC and dACC. As predicted, dACC activity subsequent to LDLPFC activity distinguished congruent and incongruent conditions on the Stroop task. Furthermore, when LDLPFC activity was low, the level of dACC activity was related to performance outcome. These results demonstrate that dACC responds to attentional demand in a flexible manner that is dependent on the level of LDLPFC activity earlier in a trial. Overall, results were consistent with the temporal course of regional brain function proposed by the cascade-of-control model. Copyright 2009 Elsevier Inc. All rights reserved.

Enhanced intelligent driver model to access the impact of driving strategies on traffic capacity.

PubMed

Kesting, Arne; Treiber, Martin; Helbing, Dirk

2010-10-13

With an increasing number of vehicles equipped with adaptive cruise control (ACC), the impact of such vehicles on the collective dynamics of traffic flow becomes relevant. By means of simulation, we investigate the influence of variable percentages of ACC vehicles on traffic flow characteristics. For simulating the ACC vehicles, we propose a new car-following model that also serves as the basis of an ACC implementation in real cars. The model is based on the intelligent driver model (IDM) and inherits its intuitive behavioural parameters: desired velocity, acceleration, comfortable deceleration and desired minimum time headway. It eliminates, however, the sometimes unrealistic behaviour of the IDM in cut-in situations with ensuing small gaps that regularly are caused by lane changes of other vehicles in dense or congested traffic. We simulate the influence of different ACC strategies on the maximum capacity before breakdown and the (dynamic) bottleneck capacity after breakdown. With a suitable strategy, we find sensitivities of the order of 0.3, i.e. 1 per cent more ACC vehicles will lead to an increase in the capacities by about 0.3 per cent. This sensitivity multiplies when considering travel times at actual breakdowns.

Estimation of Free-Living Energy Expenditure by Heart Rate and Movement Sensing: A Doubly-Labelled Water Study.

PubMed

Brage, Søren; Westgate, Kate; Franks, Paul W; Stegle, Oliver; Wright, Antony; Ekelund, Ulf; Wareham, Nicholas J

2015-01-01

Accurate assessment of energy expenditure (EE) is important for the study of energy balance and metabolic disorders. Combined heart rate (HR) and acceleration (ACC) sensing may increase precision of physical activity EE (PAEE) which is the most variable component of total EE (TEE). To evaluate estimates of EE using ACC and HR data with or without individual calibration against doubly-labelled water (DLW) estimates of EE. 23 women and 23 men (22-55 yrs, 48-104 kg, 8-46%body fat) underwent 45-min resting EE (REE) measurement and completed a 20-min treadmill test, an 8-min step test, and a 3-min walk test for individual calibration. ACC and HR were monitored and TEE measured over 14 days using DLW. Diet-induced thermogenesis (DIT) was calculated from food-frequency questionnaire. PAEE (TEE ÷ REE ÷ DIT) and TEE were compared to estimates from ACC and HR using bias, root mean square error (RMSE), and correlation statistics. Mean(SD) measured PAEE and TEE were 66(25) kJ·day(-1)·kg(-1), and 12(2.6) MJ·day(-1), respectively. Estimated PAEE from ACC was 54(15) kJ·day(-1)·kg(-1) (p<0.001), with RMSE 24 kJ·day(-1)·kg(-1) and correlation r = 0.52. PAEE estimated from HR and ACC+HR with treadmill calibration were 67(42) and 69(25) kJ·day(-1)·kg(-1) (bias non-significant), with RMSE 34 and 20 kJ·day(-1)·kg(-1) and correlations r = 0.58 and r = 0.67, respectively. Similar results were obtained with step-calibrated and walk-calibrated models, whereas non-calibrated models were less precise (RMSE: 37 and 24 kJ·day(-1)·kg(-1), r = 0.40 and r = 0.55). TEE models also had high validity, with biases <5%, and correlations r = 0.71 (ACC), r = 0.66-0.76 (HR), and r = 0.76-0.83 (ACC+HR). Both accelerometry and heart rate may be used to estimate EE in adult European men and women, with improved precision if combined and if heart rate is individually calibrated.

Clarifying anti-reflexivity: conservative opposition to impact science and scientific evidence

NASA Astrophysics Data System (ADS)

Dunlap, Riley E.

2014-01-01

The recent study reported by McCright et al (2013 Environ. Res. Lett. 8 044029) extends current research on conservatives’ distrust of science by distinguishing between public trust in production versus impact scientists (i.e. those whose work yields new technologies and marketable products versus those assessing the health and environmental impacts of such technologies and products). As expected, they find that conservatives are significantly less trustful of impact scientists but somewhat more trustful of production scientists. In the process they provide support for the Anti-Reflexivity Thesis, a perspective that attributes conservatives’ (and Republicans’) denial of anthropogenic climate change (ACC) and other environmental problems and attacks on climate/environmental science to their staunch commitment to protecting the current system of economic production. McCright et al’s innovative study deserves replication, and their approach should prove useful in accounting for divergent views of ACC. It is also important to keep in mind that anti-reflexivity is an institutional and structural issue, becoming more consequential when it is employed by political elites such as the George W Bush Administration in the US. Institutional anti-reflexivity is further illustrated by the widespread denial of ACC and a range of other problems among current Republican members of the US Congress.

Adsorption/electrosorption of catechol and resorcinol onto high area activated carbon cloth.

PubMed

Bayram, Edip; Hoda, Numan; Ayranci, Erol

2009-09-15

Removal of catechol and resorcinol from aqueous solutions by adsorption and electrosorption onto high area activated carbon cloth (ACC) was investigated. Kinetics of both adsorption and electrosorption were followed by in-situ UV-spectroscopic method and the data were treated according to pseudo-first-order, pseudo-second-order and intraparticle diffusion models. It was found that the adsorption and electrosorption of these compounds onto ACC follows pseudo-second-order model. pH changes during adsorption and electrosorption were followed and discussed with regard to the interaction between ACC and adsorbate molecules, utilizing the pH(pzc) value of ACC. An electrodesorption experiment was conducted to explore the possibility of regeneration of ACC. Adsorption isotherms were derived at 25 degrees C on the basis of batch analysis. The fits of experimental isotherm data to the well-known Freundlich, Langmuir and Tempkin models were examined.

Racial Bias in Neural Response for Pain Is Modulated by Minimal Group

PubMed Central

Shen, Fengtao; Hu, Yang; Fan, Mingxia; Wang, Huimin; Wang, Zhaoxin

2018-01-01

Whether empathic racial bias could be modulated is a subject of intense interest. The present study was carried out to explore whether empathic racial bias for pain is modulated by minimal group. Chinese/Western faces with neutral expressions receiving painful (needle penetration) or non-painful (Q-tip touch) stimulation were presented. Participants were asked to rate the pain intensity felt by Chinese/Western models of ingroup/outgroup members. Their implicit racial bias were also measured. Two lines of evidence indicated that the anterior cingulate cortex (ACC) was modulated by racial bias: (1) Chinese models elicited stronger activity than Western did in the ACC, and (2) activity in the ACC was modulated by implicit racial bias. Whereas the right anterior insula (rAI) were modulated by ingroup bias, in which ingroup member elicited stronger activity than outgroup member did. Furthermore, activity in the ACC was modulated by activity of rAI (i.e., ingroup bias) in the pain condition, while activity in the rAI was modulated by activity of ACC (i.e., racial bias) in the nopain condition. Our results provide evidence that there are different neural correlates for racial bias and ingroup bias, and neural racial bias for pain can be modulated by minimal group. PMID:29379429

Racial Bias in Neural Response for Pain Is Modulated by Minimal Group.

PubMed

Shen, Fengtao; Hu, Yang; Fan, Mingxia; Wang, Huimin; Wang, Zhaoxin

2017-01-01

Whether empathic racial bias could be modulated is a subject of intense interest. The present study was carried out to explore whether empathic racial bias for pain is modulated by minimal group. Chinese/Western faces with neutral expressions receiving painful (needle penetration) or non-painful (Q-tip touch) stimulation were presented. Participants were asked to rate the pain intensity felt by Chinese/Western models of ingroup/outgroup members. Their implicit racial bias were also measured. Two lines of evidence indicated that the anterior cingulate cortex (ACC) was modulated by racial bias: (1) Chinese models elicited stronger activity than Western did in the ACC, and (2) activity in the ACC was modulated by implicit racial bias. Whereas the right anterior insula (rAI) were modulated by ingroup bias, in which ingroup member elicited stronger activity than outgroup member did. Furthermore, activity in the ACC was modulated by activity of rAI (i.e., ingroup bias) in the pain condition, while activity in the rAI was modulated by activity of ACC (i.e., racial bias) in the nopain condition. Our results provide evidence that there are different neural correlates for racial bias and ingroup bias, and neural racial bias for pain can be modulated by minimal group.

Steady-state kinetics of substrate binding and iron release in tomato ACC oxidase.

PubMed

Thrower, J S; Blalock, R; Klinman, J P

2001-08-14

1-Aminocyclopropane-1-carboxylate oxidase (ACC oxidase) catalyzes the last step in the biosynthetic pathway of the plant hormone, ethylene. This unusual reaction results in the oxidative ring cleavage of 1-aminocyclopropane carboxylate (ACC) into ethylene, cyanide, and CO2 and requires ferrous ion, ascorbate, and molecular oxygen for catalysis. A new purification procedure and assay method have been developed for tomato ACC oxidase that result in greatly increased enzymatic activity. This method allowed us to determine the rate of iron release from the enzyme and the effect of the activator, CO2, on this rate. Initial velocity studies support an ordered kinetic mechanism where ACC binds first followed by O2; ascorbate can bind after O2 or possibly before ACC. This kinetic mechanism differs from one recently proposed for the ACC oxidase from avocado.

BH3-mimetic small molecule inhibits the growth and recurrence of adenoid cystic carcinoma

PubMed Central

Acasigua, Gerson A.; Warner, Kristy A.; Nör, Felipe; Helman, Joseph; Pearson, Alexander T.; Fossati, Anna C.; Wang, Shaomeng; Nör, Jacques E.

2015-01-01

Objectives To evaluate the anti-tumor effect of BM-1197, a new potent and highly specific small molecule inhibitor of Bcl-2/Bcl-xL, in preclinical models of human adenoid cystic carcinoma (ACC). Methods Low passage primary human adenoid cystic carcinoma cells (UM-HACC-2A,-2B,-5,-6) and patient-derived xenograft (PDX) models (UM-PDX-HACC) were developed from surgical specimens obtained from 4 patients. The effect of BM-1197 on cell viability and cell cycle were evaluated in vitro using this panel of low passage ACC cells. The effect of BM-1197 on tumor growth, recurrence and tumor cell apoptosis in vivo was evaluated with the PDX model of ACC (UM-PDX-HACC-5). Results Exposure of low passage primary human ACC cells to BM-1197 mediated an IC50 of 0.92-2.82 μM. This correlated with an increase in the fraction of apoptotic cells (p<0.0001) and an increase in caspase-3 activity (p<0.0001), but no noticeable differences in cell cycle (p>0.05). In vivo, BM-1197 inhibited tumor growth (p=0.0256) and induced tumor cell apoptosis (p=0.0165) without causing significant systemic toxicities, as determined by mouse weight over time. Surprisingly, weekly BM-1197 decreased the incidence of tumor recurrence (p=0.0297), as determined by Kaplan-Meier analysis. Conclusion These data demonstrated that single agent BM-1197 induces apoptosis and inhibits tumor growth in preclinical models of adenoid cystic carcinoma. Notably, single agent BM-1197 inhibited tumor recurrence, which is considered a major clinical challenge in the clinical management of adenoid cystic carcinoma. Collectively, these results suggest that patients with adenoid cystic carcinoma might benefit from therapy with a BH3-mimetic small molecule. PMID:26121939

Inventory of File gfs.t06z.smartguam06.tm00.grib2

Science.gov Websites

(0=sea, 1=land) [Proportion] 009 surface APCP 3-6 hour acc Total Precipitation [kg/m^2] 010 surface ] 020 surface TMAX 3-6 hour acc Maximum Temperature [K] 021 surface TMIN 3-6 hour acc Minimum Temperature [K] 022 surface MAXRH 3-6 hour acc Maximum Relative Humidity [%] 023 surface MINRH 3-6 hour acc

Large Area Crop Inventory Experiment (LACIE). Evaluation of the LACIE transition year crop calendar model. [Wheat growth in the Great Plains Corridor, North America

NASA Technical Reports Server (NTRS)

Cheffin, R. E.; Woolley, S. K. (Principal Investigator)

1979-01-01

The author has identified the following significant results. The estimates of developmental stage dates from the LACIE adjustable crop calendar (ACC) winter wheat model was somewhat more accurate than the historical crop calendar after jointing. The ACC winter wheat model was not so accurate for the Texas Panhandle as it was for the other areas of the USPG-7 because dry soil conditions delayed fall planting in the Panhandle. Since the LACIE ACC winter wheat model does not contain a moisture term and it was started with historical planting dates, lengthy delays in planting mean that the ACC model will probably be started early and will estimate the developmental growth stages to occur too early in the season. The LACIE ACC spring wheat model was also started early in most areas because of late planting due to fields wet from melting snow and rain. The starter model used to estimate spring planting dates was not accurate under these wet soil conditions and tended to predict the developmental stages to occur earlier than the dates observed in the fields.

X-shooter spectroscopy of young stellar objects. IV. Accretion in low-mass stars and substellar objects in Lupus

NASA Astrophysics Data System (ADS)

Alcalá, J. M.; Natta, A.; Manara, C. F.; Spezzi, L.; Stelzer, B.; Frasca, A.; Biazzo, K.; Covino, E.; Randich, S.; Rigliaco, E.; Testi, L.; Comerón, F.; Cupani, G.; D'Elia, V.

2014-01-01

We present VLT/X-shooter observations of a sample of 36 accreting low-mass stellar and substellar objects (YSOs) in the Lupus star-forming region, spanning a range in mass from ~0.03 to ~1.2 M⊙, but mostly with 0.1 M⊙

Pathways of upwelling deep waters to the surface of the Southern Ocean

NASA Astrophysics Data System (ADS)

Tamsitt, Veronica; Drake, Henri; Morrison, Adele; Talley, Lynne; Dufour, Carolina; Gray, Alison; Griffies, Stephen; Mazloff, Matthew; Sarmiento, Jorge; Wang, Jinbo; Weijer, Wilbert

2017-04-01

Upwelling of Atlantic, Indian and Pacific deep waters to the sea surface in the Southern Ocean closes the global overturning circulation and is fundamentally important for oceanic uptake of anthropogenic carbon and heat, nutrient resupply for sustaining oceanic biological production, and the melt rate of ice shelves. Here we go beyond the two-dimensional view of Southern Ocean upwelling, to show detailed Southern Ocean upwelling pathways in three dimensions, using hydrographic observations and particle tracking in high-resolution ocean and climate models. The northern deep waters enter the Antarctic Circumpolar Current (ACC) via narrow southward currents along the boundaries of the three ocean basins, before spiraling southeastward and upward through the ACC. Upwelling is greatly enhanced at five major topographic features, associated with vigorous mesoscale eddy activity. Deep water reaches the upper ocean predominantly south of the southern ACC boundary, with a spatially nonuniform distribution, regionalizing warm water supply to Antarctic ice shelves and the delivery of nutrient and carbon-rich water to the sea surface. The timescale for half of the deep water to upwell from 30°S to the mixed layer is on the order of 60-90 years, which has important implications for the timescale for signals to propagate through the deep ocean. In addition, we quantify the diabatic transformation along particle trajectories, to identify where diabatic processes are important along the upwelling pathways.

Biotin augments acetyl CoA carboxylase 2 gene expression in the hypothalamus, leading to the suppression of food intake in mice.

PubMed

Sone, Hideyuki; Kamiyama, Shin; Higuchi, Mutsumi; Fujino, Kaho; Kubo, Shizuka; Miyazawa, Masami; Shirato, Saya; Hiroi, Yuka; Shiozawa, Kota

2016-07-29

It is known that biotin prevents the development of diabetes by increasing the functions of pancreatic beta-cells and improving insulin sensitivity in the periphery. However, its anti-obesity effects such as anorectic effects remain to be clarified. Acetyl CoA carboxylase (ACC), a biotin-dependent enzyme, has two isoforms (ACC1 and ACC2) and serves to catalyze the reaction of acetyl CoA to malonyl CoA. In the hypothalamus, ACC2 increases the production of malonyl CoA, which acts as a satiety signal. In this study, we investigated whether biotin increases the gene expression of ACC2 in the hypothalamus and suppresses food intake in mice administered excessive biotin. Food intake was significantly decreased by biotin, but plasma regulators of appetite, including glucose, ghrelin, and leptin, were not affected. On the other hand, biotin notably accumulated in the hypothalamus and enhanced ACC2 gene expression there, but it did not change the gene expression of ACC1, malonyl CoA decarboxylase (a malonyl CoA-degrading enzyme), and AMP-activated protein kinase α-2 (an ACC-inhibitory enzyme). These findings strongly suggest that biotin potentiates the suppression of appetite by upregulating ACC2 gene expression in the hypothalamus. This effect of biotin may contribute to the prevention of diabetes by biotin treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

The ACC/AHA 2013 pooled cohort equations compared to a Korean Risk Prediction Model for atherosclerotic cardiovascular disease.

PubMed

Jung, Keum Ji; Jang, Yangsoo; Oh, Dong Joo; Oh, Byung-Hee; Lee, Sang Hoon; Park, Seong-Wook; Seung, Ki-Bae; Kim, Hong-Kyu; Yun, Young Duk; Choi, Sung Hee; Sung, Jidong; Lee, Tae-Yong; Kim, Sung Hi; Koh, Sang Baek; Kim, Moon Chan; Chang Kim, Hyeon; Kimm, Heejin; Nam, Chungmo; Park, Sungha; Jee, Sun Ha

2015-09-01

To evaluate the performance of the American College of Cardiology/American Heart Association (ACC/AHA) 2013 Pooled Cohort Equations in the Korean Heart Study (KHS) population and to develop a Korean Risk Prediction Model (KRPM) for atherosclerotic cardiovascular disease (ASCVD) events. The KHS cohort included 200,010 Korean adults aged 40-79 years who were free from ASCVD at baseline. Discrimination, calibration, and recalibration of the ACC/AHA Equations in predicting 10-year ASCVD risk in the KHS cohort were evaluated. The KRPM was derived using Cox model coefficients, mean risk factor values, and mean incidences from the KHS cohort. In the discriminatory analysis, the ACC/AHA Equations' White and African-American (AA) models moderately distinguished cases from non-cases, and were similar to the KRPM: For men, the area under the receiver operating characteristic curve (AUROCs) were 0.727 (White model), 0.725 (AA model), and 0.741 (KRPM); for women, the corresponding AUROCs were 0.738, 0.739, and 0.745. Absolute 10-year ASCVD risk for men in the KHS cohort was overestimated by 56.5% (White model) and 74.1% (AA model), while the risk for women was underestimated by 27.9% (White model) and overestimated by 29.1% (AA model). Recalibration of the ACC/AHA Equations did not affect discriminatory ability but improved calibration substantially, especially in men in the White model. Of the three ASCVD risk prediction models, the KRPM showed best calibration. The ACC/AHA Equations should not be directly applied for ASCVD risk prediction in a Korean population. The KRPM showed best predictive ability for ASCVD risk. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Parotid adenoid cystic carcinoma: Retrospective single institute analysis.

PubMed

Mannelli, Giuditta; Cecconi, Lorenzo; Fasolati, Martina; Santoro, Roberto; Franchi, Alessandro; Gallo, Oreste

Adenoid cystic carcinoma (ACC) is a uncommon salivary malignant tumor. Our aim was to review our experience with parotid ACC, to identify clinical-pathological parameters predictive for outcome. We retrospectively reviewed 228 patients affected by parotid gland carcinomas surgically treated at our Institution. Forty-four ACC were included in this study. Multivariate analysis risk models were built to predict recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and disease free survival (DFS). Twenty-one patients (47.7%) died from ACC and 2.3% for other causes. The 41% presented local-regional recurrence, with a regional-RFP rate of 93%, and the 34% reported distant metastases (DM). The five and ten-year OS rates were 74% and 50%, respectively. Recurrences were mainly influenced by the presence of perineural invasion and nerve paralysis, whilst female gender and age<50 were predictors for good prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Developing an appropriate staff mix for anticoagulation clinics: functional job analysis approach

NASA Astrophysics Data System (ADS)

Hailemariam, Desta A.; Shan, Xiaojun; Chung, Sung H.; Khasawneh, Mohammad T.; Lukesh, William; Park, Angela; Rose, Adam

2018-05-01

Anticoagulation clinics (ACCs) are specialty clinics that manage patients with blood clotting problems. Since labor costs usually account for a substantial portion of a healthcare organization's budget, optimizing the number and types of staff required was often the focus, especially for ACCs, where labor-intensive staff-patient interactions occur. A significant portion of tasks performed by clinical pharmacists might be completed by clinical pharmacist technicians, which are less-expensive resources. While nurse staffing models for a hospital inpatient unit are well established, these models are not readily applicable to staffing ACCs. Therefore, the objective of this paper is to develop a framework for determining the right staff mix of clinical pharmacists and clinical pharmacy technicians that increases the efficiency of care delivery process and improves the productivity of ACC staff. A framework is developed and applied to build a semi-automated full-time equivalent (FTE) calculator and compare various staffing scenarios using a simulation model. The FTE calculator provides the right staff mix for a given staff utilization target. Data collected from the ACCs at VA Boston Healthcare System is used to illustrate the FTE calculator and the simulation model. The result of the simulation model can be used by ACC managers to easily determine the number of FTEs of clinical pharmacists and clinical pharmacy technicians required to reach the target utilization and the corresponding staffing cost.

Expression of the dopaminergic D1 and D2 receptors in the anterior cingulate cortex in a model of neuropathic pain

PubMed Central

2011-01-01

Background The anterior cingulate cortex (ACC) has been related to the affective component of pain. Dopaminergic mesocortical circuits, including the ACC, are able to inhibit neuropathic nociception measured as autotomy behaviour. We determined the changes in dopamine D1 and D2 (D1R and D2R) receptor expression in the ACC (cg1 and cg2) in an animal model of neuropathic pain. The neuropathic group had noxious heat applied in the right hind paw followed 30 min. later by right sciatic denervation. Autotomy score (AS) was recorded for eight days and subsequently classified in low, medium and high AS groups. The control consisted of naïve animals. A semiquantitative RT-PCR procedure was done to determine mRNA levels for D1R and D2R in cg1 and cg2, and protein levels were measured by Western Blot. Results The results of D1R mRNA in cg1 showed a decrease in all groups. D2R mRNA levels in cg1 decreased in low AS and increased in medium and high AS. Regarding D1R in cg2, there was an increase in all groups. D2R expression levels in cg2 decreased in all groups. In cg1, the D2R mRNA correlated positively with autotomy behaviour. Protein levels of D2R in cg1 increased in all groups but to a higher degree in low AS. In cg2 D2R protein only decreased discretely. D1R protein was not found in either ACC region. Conclusions This is the first evidence of an increase of inhibitory dopaminergic receptor (D2R) mRNA and protein in cg1 in correlation with nociceptive behaviour in a neuropathic model of pain in the rat. PMID:22171983

Computational Models of Anterior Cingulate Cortex: At the Crossroads between Prediction and Effort.

PubMed

Vassena, Eliana; Holroyd, Clay B; Alexander, William H

2017-01-01

In the last two decades the anterior cingulate cortex (ACC) has become one of the most investigated areas of the brain. Extensive neuroimaging evidence suggests countless functions for this region, ranging from conflict and error coding, to social cognition, pain and effortful control. In response to this burgeoning amount of data, a proliferation of computational models has tried to characterize the neurocognitive architecture of ACC. Early seminal models provided a computational explanation for a relatively circumscribed set of empirical findings, mainly accounting for EEG and fMRI evidence. More recent models have focused on ACC's contribution to effortful control. In parallel to these developments, several proposals attempted to explain within a single computational framework a wider variety of empirical findings that span different cognitive processes and experimental modalities. Here we critically evaluate these modeling attempts, highlighting the continued need to reconcile the array of disparate ACC observations within a coherent, unifying framework.

Effect of 1-aminocyclopropane-1-carboxylic acid on the production of ethylene in senescing flowers of Ipomoea tricolor Cav

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konze, J.R.; Jones, J.F.; Boller, T.

1980-10-01

Application of 1-aminocyclopropane-1-carboxylic acid (ACC) to rib segments excised from flowers of Ipomoea tricolor Cav. resulted in the formation of C/sub 2/H/sub 4/ in greater quantities than produced under natural conditions. The ability of ACC to enhance C/sub 2/H/sub 4/ production was independent of the physiological age of the tissue and its capacity to synthesize C/sub 2/H/sub 4/ without applied ACC. When ACC was fed to rib segments that had been treated with (/sup 14/C)methionine, incorporation of radioactivity into C/sub 2/H/sub 4/ was reduced by 80%. Aminoethoxyvinylglycine and aminooxyacetic acid inhibited C/sub 2/H/sub 4/ production in rib segments of I.more » tricolor but had no effect on ACC-enhanced C/sub 2/H/sub 4/ production. Protoplasts obtained from flower tissue of I. tricolor did not form C/sub 2/H/sub 4/, even when incubated with methionine or selenomethionine. They produced C/sub 2/H/sub 4/ upon incubation with ACC, however. ACC-dependent C/sub 2/H/sub 4/ production in protoplasts was inhibited by n-propyl gallate, AgCl, CoCl/sub 2/, KCN, Na/sub 2/S, and NaN/sub 3/. ACC-dependent C/sub 2/H/sub 4/ synthesis in rib segments and protoplasts was dependent on O/sub 2/, the K/sub m/ for O/sub 2/ being 1.0 to 1.4% (v/v). These results confirm the following pathway for C/sub 2/H/sub 4/ biosynthesis in I. tricolor: methionine (selenomethionine) ..-->..S-adenosylmethionine (selenoadenosylmethionine) ..-->.. ACC ..-->.. C/sub 2/H/sub 4/.« less

Sensitivity and specificity of univariate MRI analysis of experimentally degraded cartilage under clinical imaging conditions.

PubMed

Lukas, Vanessa A; Fishbein, Kenneth W; Reiter, David A; Lin, Ping-Chang; Schneider, Erika; Spencer, Richard G

2015-07-01

To evaluate the sensitivity and specificity of classification of pathomimetically degraded bovine nasal cartilage at 3 Tesla and 37°C using univariate MRI measurements of both pure parameter values and intensities of parameter-weighted images. Pre- and posttrypsin degradation values of T1 , T2 , T2 *, magnetization transfer ratio (MTR), and apparent diffusion coefficient (ADC), and corresponding weighted images, were analyzed. Classification based on the Euclidean distance was performed and the quality of classification was assessed through sensitivity, specificity and accuracy (ACC). The classifiers with the highest accuracy values were ADC (ACC = 0.82 ± 0.06), MTR (ACC = 0.78 ± 0.06), T1 (ACC = 0.99 ± 0.01), T2 derived from a three-dimensional (3D) spin-echo sequence (ACC = 0.74 ± 0.05), and T2 derived from a 2D spin-echo sequence (ACC = 0.77 ± 0.06), along with two of the diffusion-weighted signal intensities (b = 333 s/mm(2) : ACC = 0.80 ± 0.05; b = 666 s/mm(2) : ACC = 0.85 ± 0.04). In particular, T1 values differed substantially between the groups, resulting in atypically high classification accuracy. The second-best classifier, diffusion weighting with b = 666 s/mm(2) , as well as all other parameters evaluated, exhibited substantial overlap between pre- and postdegradation groups, resulting in decreased accuracies. Classification according to T1 values showed excellent test characteristics (ACC = 0.99), with several other parameters also showing reasonable performance (ACC > 0.70). Of these, diffusion weighting is particularly promising as a potentially practical clinical modality. As in previous work, we again find that highly statistically significant group mean differences do not necessarily translate into accurate clinical classification rules. © 2014 Wiley Periodicals, Inc.

Are general practice characteristics predictors of good glycaemic control in patients with diabetes? A cross-sectional study.

PubMed

Esterman, Adrian J; Fountaine, Tim; McDermott, Robyn

2016-01-18

To determine whether certain characteristics of general practices are associated with good glycaemic control in patients with diabetes and with completing an annual cycle of care (ACC). Our cross-sectional analysis used baseline data from the Australian Diabetes Care Project conducted between 2011 and 2014. Practice characteristics were self-reported. Characteristics of the patients that were assessed included glycaemic control (HbA1c level ≤ 53 mmol/mol), age, sex, duration of diabetes, socio-economic disadvantage (SEIFA) score, the complexity of the patient's condition, and whether the patient had completed an ACC for diabetes in the past 18 months. Clustered logistic regression was used to establish predictors of glycaemic control and a completed ACC. Data were available from 147 general practices and 5455 patients with established type 1 or type 2 diabetes in three Australian states. After adjustment for other patient characteristics, only the patient completing an ACC was statistically significant as a predictor of glycaemic control (P = 0.011). In a multivariate model, the practice having a chronic disease-focused practice nurse (P = 0.036) and running educational events for patients with diabetes (P = 0.004) were statistically significant predictors of the patient having complete an ACC. Patient characteristics are moderately good predictors of whether the patient is in glycaemic control, whereas practice characteristics appear to predict only the likelihood of patients completing an ACC. The ACC is an established indicator of good diabetes management. This is the first study to report a positive association between having completed an ACC and the patient being in glycaemic control.

Nitroimidazoles adsorption on activated carbon cloth from aqueous solution.

PubMed

Ocampo-Pérez, R; Orellana-Garcia, F; Sánchez-Polo, M; Rivera-Utrilla, J; Velo-Gala, I; López-Ramón, M V; Alvarez-Merino, M A

2013-07-01

The objective of this study was to analyze the equilibrium and adsorption kinetics of nitroimidazoles on activated carbon cloth (ACC), determining the main interactions responsible for the adsorption process and the diffusion mechanism of these compounds on this material. The influence of the different operational variables, such as ionic strength, pH, temperature, and type of water (ultrapure, surface, and waste), was also studied. The results obtained show that the ACC has a high capacity to adsorb nitroimidazoles in aqueous solution. Electrostatic interactions play an important role at pH<3, which favors the repulsive forces between dimetridazole or metronidazole and the ACC surface. The formation of hydrogen bonds and dispersive interactions play the predominant role at higher pH values. Modifications of the ACC with NH3, K2S2O8, and O3 demonstrated that its surface chemistry plays a predominant role in nitroimidazole adsorption on this material. The adsorption capacity of ACC is considerably high in surface waters and reduced in urban wastewater, due to the levels of alkalinity and dissolved organic matter present in the different types of water. Finally, the results of applying kinetic models revealed that the global adsorption rate of dimetridazole and metronidazole is controlled by intraparticle diffusion. Copyright © 2013 Elsevier Inc. All rights reserved.

Identification of acid-sensing ion channels in adenoid cystic carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ye Jinhai; Department of Oral and Maxillofacial Surgery, School of Stomatology, Nanjing Medical University, Research Institute of Stomatology, Nanjing 210029; Gao Jun

2007-04-20

Tissue acidosis is an important feature of tumor. The response of adenoid cystic carcinoma (ACC) cells to acidic solution was studied using whole-cell patch-clamp recording in the current study. An inward, amiloride-sensitive Na{sup +} current was identified in cultured ACC-2 cells while not in normal human salivary gland epithelial cells. Electrophysiological and pharmacological properties of the currents suggest that heteromeric acid-sensing ion channels (ASICs) containing 2a and 3 may be responsible for the proton-induced currents in the majority of ACC-2 cells. Consistent with it, analyses of RT-PCR and Western blotting demonstrated the presences of ASIC2a and 3 in ACC-2 cells.more » Furthermore, we observed the enhanced expression of ASIC2a and 3 in the sample of ACC tissues. These results indicate that the functional expression of ASICs is characteristic feature of ACC cells.« less

Analysis of Arabidopsis Accessions Hypersensitive to a Loss of Chloroplast Translation1[OPEN

PubMed Central

Parker, Nicole; Wang, Yixing; Meinke, David

2016-01-01

Natural accessions of Arabidopsis (Arabidopsis thaliana) differ in their ability to tolerate a loss of chloroplast translation. These differences can be attributed in part to variation in a duplicated nuclear gene (ACC2) that targets homomeric acetyl-coenzyme A carboxylase (ACCase) to plastids. This functional redundancy allows limited fatty acid biosynthesis to occur in the absence of heteromeric ACCase, which is encoded in part by the plastid genome. In the presence of functional ACC2, tolerant alleles of several nuclear genes, not yet identified, enhance the growth of seedlings and embryos disrupted in chloroplast translation. ACC2 knockout mutants, by contrast, are hypersensitive. Here we describe an expanded search for hypersensitive accessions of Arabidopsis, evaluate whether all of these accessions are defective in ACC2, and characterize genotype-to-phenotype relationships for homomeric ACCase variants identified among 855 accessions with sequenced genomes. Null alleles with ACC2 nonsense mutations, frameshift mutations, small deletions, genomic rearrangements, and defects in RNA splicing are included among the most sensitive accessions examined. By contrast, most missense mutations affecting highly conserved residues failed to eliminate ACC2 function. Several accessions were identified where sensitivity could not be attributed to a defect in either ACC2 or Tic20-IV, the chloroplast membrane channel required for ACC2 uptake. Overall, these results underscore the central role of ACC2 in mediating Arabidopsis response to a loss of chloroplast translation, highlight future applications of this system to analyzing chloroplast protein import, and provide valuable insights into the mutational landscape of an important metabolic enzyme that is highly conserved throughout eukaryotes. PMID:27707889

Observed Temporal and Spatial Variability in the Marine Environment at the Sub-Antarctic Prince Edward Islands - Evidence of a Changing Climate?

NASA Astrophysics Data System (ADS)

Asdar, S.; Deshayes, J.; Ansorge, I. J.

2016-02-01

The sub-Antarctic Prince Edward Islands (PEI) (47°S,38°E) are classified as isolated, hostile, impoverished regions, in which the terrestrial and marine ecosystems are relatively simple and extremely sensitive to perturbations. Their location between the Sub-Antarctic Front (SAF) and the Antarctic Polar Front (APF), bordering the Antarctic Circumpolar Current (ACC) provides an ideal natural laboratory for studying how organisms, ecological processes and ecosystems respond to a changing ocean climate in the Southern Ocean. Recent studies have proposed that climate changes reported at the PEI may correspond in time to a southward shift of the ACC and in particular of the SAF. This southward migration in the geographic position is likely to coincide with dramatic changes in the distribution of species and total productivity of this region. This study focuses on the inter-comparison of observations available at these islands. Using spectral analysis which is a study of the frequency domain characteristics of a process, we first determine the dominant characteristics of both the temporal and spatial variability of physical and biogeochemical properties. In doing so the authors are able to determine whether and how these indices of variability interact with one another in order to understand better the mechanisms underpinning this variability, i.e. the seasonal zonal migrations associated with the SAF. Additionally, we include in our analysis recent data from 2 ADCP moorings deployed between the islands from 2014 to 2015. These in-situ observations of circulation and hydrography in the vicinity of the islands provide a unique opportunity to establish a better understanding of how large scale climatic variability may impact local conditions, and more importantly its influence on the fragile ecosystem surrounding the PEI.

Improved Analysis of Earth System Models and Observations using Simple Climate Models

NASA Astrophysics Data System (ADS)

Nadiga, B. T.; Urban, N. M.

2016-12-01

Earth system models (ESM) are the most comprehensive tools we have to study climate change and develop climate projections. However, the computational infrastructure required and the cost incurred in running such ESMs precludes direct use of such models in conjunction with a wide variety of tools that can further our understanding of climate. Here we are referring to tools that range from dynamical systems tools that give insight into underlying flow structure and topology to tools that come from various applied mathematical and statistical techniques and are central to quantifying stability, sensitivity, uncertainty and predictability to machine learning tools that are now being rapidly developed or improved. Our approach to facilitate the use of such models is to analyze output of ESM experiments (cf. CMIP) using a range of simpler models that consider integral balances of important quantities such as mass and/or energy in a Bayesian framework.We highlight the use of this approach in the context of the uptake of heat by the world oceans in the ongoing global warming. Indeed, since in excess of 90% of the anomalous radiative forcing due greenhouse gas emissions is sequestered in the world oceans, the nature of ocean heat uptake crucially determines the surface warming that is realized (cf. climate sensitivity). Nevertheless, ESMs themselves are never run long enough to directly assess climate sensitivity. So, we consider a range of models based on integral balances--balances that have to be realized in all first-principles based models of the climate system including the most detailed state-of-the art climate simulations. The models range from simple models of energy balance to those that consider dynamically important ocean processes such as the conveyor-belt circulation (Meridional Overturning Circulation, MOC), North Atlantic Deep Water (NADW) formation, Antarctic Circumpolar Current (ACC) and eddy mixing. Results from Bayesian analysis of such models using both ESM experiments and actual observations are presented. One such result points to the importance of direct sequestration of heat below 700 m, a process that is not allowed for in the simple models that have been traditionally used to deduce climate sensitivity.

GAD65 Promoter Polymorphism rs2236418 Modulates Harm Avoidance in Women via Inhibition/Excitation Balance in the Rostral ACC.

PubMed

Colic, Lejla; Li, Meng; Demenescu, Liliana Ramona; Li, Shija; Müller, Iris; Richter, Anni; Behnisch, Gusalija; Seidenbecher, Constanze I; Speck, Oliver; Schott, Björn H; Stork, Oliver; Walter, Martin

2018-05-30

Anxiety disorders are common and debilitating conditions with higher prevalence in women. However, factors that predispose women to anxiety phenotypes are not clarified. Here we investigated potential contribution of the single nucleotide polymorphism rs2236418 in GAD2 gene to changes in regional inhibition/excitation balance, anxiety-like traits, and related neural activity in both sexes. One hundred and five healthy individuals were examined with high-field (7T) multimodal magnetic resonance imaging (MRI); including resting-state functional MRI in combination with assessment of GABA and glutamate (Glu) levels via MR spectroscopy. Regional GABA/Glu levels in anterior cingulate cortex (ACC) subregions were assessed as mediators of gene-personality interaction for the trait harm avoidance and moderation by sex was tested. In AA homozygotes, with putatively lower GAD2 promoter activity, we observed increased intrinsic neuronal activity and higher inhibition/excitation balance in pregenual ACC (pgACC) compared with G carriers. The pgACC drove a significant interaction of genotype, region, and sex, where inhibition/excitation balance was significantly reduced only in female AA carriers. This finding was specific for rs2236418 as other investigated single nucleotide polymorphisms of the GABA synthesis related enzymes ( GAD1 , GAD2 , and GLS ) were not significant. Furthermore, only in women there was a negative association of pgACC GABA/Glu ratios with harm avoidance. A moderated-mediation model revealed that pgACC GABA/Glu also mediated the association between the genotype variant and level of harm avoidance, dependent on sex. Our data thus provide new insights into the neurochemical mechanisms that control emotional endophenotypes in humans and constitute predisposing factors for the development of anxiety disorders in women. SIGNIFICANCE STATEMENT Anxiety disorders are among the most common and burdensome psychiatric disorders, with higher prevalence rates in women. The causal mechanisms are, however, poorly understood. In this study we propose a neurobiological basis that could help to explain female bias of anxiety endophenotypes. Using magnetic resonance brain imaging and personality questionnaires we show an interaction of the genetic variation rs2236418 in the GAD2 gene and sex on GABA/glutamate (Glu) balance in the pregenual anterior cingulate cortex (pgACC), a region previously connected to affect regulation and anxiety disorders. The GAD2 gene polymorphism further influenced baseline neuronal activity in the pgACC. Importantly, GABA/Glu was shown to mediate the relationship between the genetic variant and harm avoidance, however, only in women. Copyright © 2018 the authors 0270-6474/18/385068-11$15.00/0.

Dysfunctional insular connectivity during reward prediction in patients with first-episode psychosis

PubMed Central

Schmidt, André; Palaniyappan, Lena; Smieskova, Renata; Simon, Andor; Riecher-Rössler, Anita; Lang, Undine E.; Fusar-Poli, Paolo; McGuire, Philip; Borgwardt, Stefan J.

2016-01-01

Background Increasing evidence indicates that psychosis is associated with abnormal reward processing. Imaging studies in patients with first-episode psychosis (FEP) have revealed reduced activity in diverse brain regions, including the ventral striatum, insula and anterior cingulate cortex (ACC), during reward prediction. However, whether these reductions in local brain activity are due to altered connectivity has rarely been explored. Methods We applied dynamic causal modelling and Bayesian model selection to fMRI data during the Salience Attribution Task to investigate whether patients with FEP showed abnormal modulation of connectivity between the ventral striatum, insula and ACC induced by rewarding cues and whether these changes were related to positive psychotic symptoms and atypical antipsychotic medication. Results The model including reward-induced modulation of insula–ACC connectivity was the best fitting model in each group. Compared with healthy controls (n = 19), patients with FEP (n = 29) revealed reduced right insula–ACC connectivity. After subdividing patients according to current antipsychotic medication, we found that the reduced insula–ACC connectivity relative to healthy controls was observed only in untreated patients (n = 17), not in patients treated with antipsychotics (n = 12), and that it correlated negatively with unusual thought content in untreated patients with FEP. Limitations The modest sample size of untreated patients with FEP was a limitation of our study. Conclusion This study indicates that insula–ACC connectivity during reward prediction is reduced in untreated patients with FEP and related to the formation of positive psychotic symptoms. Our study further suggests that atypical antipsychotics may reverse connectivity between the insula and the ACC during reward prediction. PMID:26854756

Left ventricular outflow tract mean systolic acceleration as a surrogate for the slope of the left ventricular end-systolic pressure-volume relationship

NASA Technical Reports Server (NTRS)

Bauer, Fabrice; Jones, Michael; Shiota, Takahiro; Firstenberg, Michael S.; Qin, Jian Xin; Tsujino, Hiroyuki; Kim, Yong Jin; Sitges, Marta; Cardon, Lisa A.; Zetts, Arthur D.;

Estimation of Free-Living Energy Expenditure by Heart Rate and Movement Sensing: A Doubly-Labelled Water Study

PubMed Central

Brage, Søren; Westgate, Kate; Franks, Paul W.; Stegle, Oliver; Wright, Antony; Ekelund, Ulf; Wareham, Nicholas J.

2015-01-01

Background Accurate assessment of energy expenditure (EE) is important for the study of energy balance and metabolic disorders. Combined heart rate (HR) and acceleration (ACC) sensing may increase precision of physical activity EE (PAEE) which is the most variable component of total EE (TEE). Objective To evaluate estimates of EE using ACC and HR data with or without individual calibration against doubly-labelled water (DLW) estimates of EE. Design 23 women and 23 men (22–55 yrs, 48–104 kg, 8–46%body fat) underwent 45-min resting EE (REE) measurement and completed a 20-min treadmill test, an 8-min step test, and a 3-min walk test for individual calibration. ACC and HR were monitored and TEE measured over 14 days using DLW. Diet-induced thermogenesis (DIT) was calculated from food-frequency questionnaire. PAEE (TEE ÷ REE ÷ DIT) and TEE were compared to estimates from ACC and HR using bias, root mean square error (RMSE), and correlation statistics. Results Mean(SD) measured PAEE and TEE were 66(25) kJ·day-1·kg-1, and 12(2.6) MJ·day-1, respectively. Estimated PAEE from ACC was 54(15) kJ·day-1·kg-1 (p<0.001), with RMSE 24 kJ·day-1·kg-1 and correlation r = 0.52. PAEE estimated from HR and ACC+HR with treadmill calibration were 67(42) and 69(25) kJ·day-1·kg-1 (bias non-significant), with RMSE 34 and 20 kJ·day-1·kg-1 and correlations r = 0.58 and r = 0.67, respectively. Similar results were obtained with step-calibrated and walk-calibrated models, whereas non-calibrated models were less precise (RMSE: 37 and 24 kJ·day-1·kg-1, r = 0.40 and r = 0.55). TEE models also had high validity, with biases <5%, and correlations r = 0.71 (ACC), r = 0.66–0.76 (HR), and r = 0.76–0.83 (ACC+HR). Conclusions Both accelerometry and heart rate may be used to estimate EE in adult European men and women, with improved precision if combined and if heart rate is individually calibrated. PMID:26349056

Posttraumatic stress and alcohol use among veterans: Amygdala and anterior cingulate activation to emotional cues.

PubMed

Simons, Raluca M; Simons, Jeffrey S; Olson, Dawne; Baugh, Lee; Magnotta, Vincent; Forster, Gina

2016-11-01

This fMRI study tested a model of combat trauma, posttraumatic stress symptoms (PTSS), alcohol use, and behavioral and neural responses to emotional cues in 100 OIF/OEF/OND veterans. Multilevel structural equation models were tested for left and right dorsal ACC (dACC), rostral ACC (rACC), and amygdala blood-oxygen- level dependent responses during the emotional counting Stroop test and masked faces task. In the Stroop task, combat exposure moderated the effect of combat stimuli resulting in hyperactivation in the rACC and dACC. Activation in the left amygdala also increased in response to combat stimuli, but effects did not vary as a function of combat severity. In the masked faces task, activation patterns did not vary as a function of stimulus. However, at the between-person level, amygdala activation during the masked faces task was inversely associated with PTSS. In respect to behavioral outcomes, higher PTSS were associated with a stronger Stroop effect, suggesting greater interference associated with combat words. Results are consistent with the premise that combat trauma results in hyperactivation in the ACC in response to combat stimuli, and, via its effect on PTSS, is associated with deficits in cognitive performance in the presence of combat stimuli. Across tasks, predeployment drinking was inversely associated with activation in the dACC but not the rACC or amygdala. Drinking may be a buffering factor, or negatively reinforcing in part because of its effects on normalizing brain response following trauma exposure. Alternatively, drinking may undermine adaptive functioning of the dACC when responding to traumatic stress cues. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Withaferin A suppresses the up-regulation of acetyl-coA carboxylase 1 and skin tumor formation in a skin carcinogenesis mouse model.

PubMed

Li, Wenjuan; Zhang, Chunjing; Du, Hongyan; Huang, Vincent; Sun, Brandi; Harris, John P; Richardson, Quitin; Shen, Xinggui; Jin, Rong; Li, Guohong; Kevil, Christopher G; Gu, Xin; Shi, Runhua; Zhao, Yunfeng

2016-11-01

Withaferin A (WA), a natural product derived from Withania somnifera, has been used in traditional oriental medicines to treat neurological disorders. Recent studies have demonstrated that this compound may have a potential for cancer treatment and a clinical trial has been launched to test WA in treating melanoma. Herein, WA's chemopreventive potential was tested in a chemically-induced skin carcinogenesis mouse model. Pathological examinations revealed that WA significantly suppressed skin tumor formation. Morphological observations of the skin tissues suggest that WA suppressed cell proliferation rather than inducing apoptosis during skin carcinogenesis. Antibody Micro array analysis demonstrated that WA blocked carcinogen-induced up-regulation of acetyl-CoA carboxylase 1 (ACC1), which was further confirmed in a skin cell transformation model. Overexpression of ACC1 promoted whereas knockdown of ACC1 suppressed anchorage-independent growth and oncogene activation of transformable skin cells. Further studies demonstrated that WA inhibited tumor promotor-induced ACC1 gene transcription by suppressing the activation of activator protein 1. In melanoma cells, WA was also able to suppress the expression levels of ACC1. Finally, results using human skin cancer tissues confirmed the up-regulation of ACC1 in tumors than adjacent normal tissues. In summary, our results suggest that withaferin A may have a potential in chemoprevention and ACC1 may serve as a critical target of WA. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Can we bet on negative emissions to achieve the 2°C target even under strong carbon cycle feedbacks?

NASA Astrophysics Data System (ADS)

Tanaka, K.; Yamagata, Y.; Yokohata, T.; Emori, S.; Hanaoka, T.

2015-12-01

Negative emission technologies such as Bioenergy with Carbon dioxide Capture and Storage (BioCCS) play an ever more crucial role in meeting the 2°C stabilization target. However, such technologies are currently at their infancy and their future penetrations may fall short of the scale required to stabilize the warming. Furthermore, the overshoot in the mid-century prior to a full realization of negative emissions would give rise to a risk because such a temporal but excessive warming above 2°C might amplify itself by strengthening climate-carbon cycle feedbacks. It has not been extensively assessed yet how carbon cycle feedbacks might play out during the overshoot in the context of negative emissions. This study explores how 2°C stabilization pathways, in particular those which undergo overshoot, can be influenced by carbon cycle feedbacks and asks their climatic and economic consequences. We compute 2°C stabilization emissions scenarios under a cost-effectiveness principle, in which the total abatement costs are minimized such that the global warming is capped at 2°C. We employ a reduced-complexity model, the Aggregated Carbon Cycle, Atmospheric Chemistry, and Climate model (ACC2), which comprises a box model of the global carbon cycle, simple parameterizations of the atmospheric chemistry, and a land-ocean energy balance model. The total abatement costs are estimated from the marginal abatement cost functions for CO2, CH4, N2O, and BC.Our preliminary results show that, if carbon cycle feedbacks turn out to be stronger than what is known today, it would incur substantial abatement costs to keep up with the 2°C stabilization goal. Our results also suggest that it would be less expensive in the long run to plan for a 2°C stabilization pathway by considering strong carbon cycle feedbacks because it would cost more if we correct the emission pathway in the mid-century to adjust for unexpectedly large carbon cycle feedbacks during overshoot. Furthermore, our tentative results point to a key policy message: do not rely on negative emissions to achieve the 2°C target. It would make more sense to gear climate mitigation actions toward the stabilization target without betting on negative emissions because negative emissions might create large overshoot in case of strong feedbacks.

Therapeutic inhibition of the MDM2-p53 interaction prevents recurrence of adenoid cystic carcinomas

PubMed Central

Nör, Felipe; Warner, Kristy A.; Zhang, Zhaocheng; Acasigua, Gerson A.; Pearson, Alexander T.; Kerk, Samuel A.; Helman, Joseph; Filho, Manoel Sant’Ana; Wang, Shaomeng; Nör, Jacques E.

2016-01-01

Purpose Conventional chemotherapy has modest efficacy in advanced adenoid cystic carcinomas (ACC). Tumor recurrence is a major challenge in the management of ACC patients. Here, we evaluated the anti-tumor effect of a novel small molecule inhibitor of the MDM2-p53 interaction (MI-773) combined with Cisplatin in patient-derived xenograft (PDX) ACC tumors. Experimental design Therapeutic strategies with MI-773 and/or Cisplatin were evaluated in SCID mice harboring PDX ACC tumors (UM-PDX-HACC-5) and in low passage primary human ACC cells (UM-HACC-2A, -2B, -5, -6) in vitro. The effect of therapy on the fraction of cancer stem cells was determined by flow cytometry for ALDH activity and CD44 expression. Results Combined therapy with MI-773 with Cisplatin caused p53 activation, induction of apoptosis, and regression of ACC PDX tumors. Western blots revealed induction of MDM2, p53 and downstream p21 expression, and regulation of apoptosis-related proteins PUMA, BAX, Bcl-2, Bcl-xL and active Caspase-9 upon MI-773 treatment. Both, single-agent MI-773, and MI-773 combined with Cisplatin, decreased the fraction of cancer stem cells in PDX ACC tumors. Notably, neoadjuvant MI-773 and surgery eliminated tumor recurrences during a post-surgical follow-up of more than 300 days. In contrast, 62.5% of mice that received vehicle control presented with palpable tumor recurrences within this time period (p=0.0097). Conclusions Collectively, these data demonstrate that therapeutic inhibition of MDM2-p53 interaction by MI-773 decreased the cancer stem cell fraction, sensitized ACC xenograft tumors to Cisplatin, and eliminated tumor recurrence. These results suggest that patients with ACC might benefit from the therapeutic inhibition of the MDM2-p53 interaction. PMID:27550999

Errors without Conflict: Implications for Performance Monitoring Theories of Anterior Cingulate Cortex

ERIC Educational Resources Information Center

van Veen, V.; Holroyd, C.B.; Cohen, J.D.; Stenger, V.A.; Carter, C.S.

2004-01-01

Recent theories of the neural basis of performance monitoring have emphasized a central role for the anterior cingulate cortex (ACC). Replicating an earlier event-related potential (ERP) study, which showed an error feedback negativity that was modeled as having an ACC generator, we used event-related fMRI to investigate whether the ACC would…

24 CFR 902.5 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-04-01

...(s) for which they assumed management responsibilities. (2) ACC. The ACC makes a PHA legally... the PHA and not the RMC or AME is ultimately responsible to HUD under the ACC, the PHAS score of a PHA will be based on all of the projects covered by the ACC, including those with management operations...

Eddy-Pump: Pelagic carbon pump processes along the eddying Antarctic Polar Front in the Atlantic Sector of the Southern Ocean

NASA Astrophysics Data System (ADS)

Strass, Volker H.; Wolf-Gladrow, Dieter; Pakhomov, Evgeny A.; Klaas, Christine

2017-04-01

The Southern Ocean influences earth's climate in many ways. It hosts the largest upwelling region of the world oceans where 80% of deep waters resurface (Morrison et al., 2015). A prominent feature is the broad ring of cold water, the Antarctic Circumpolar Current (ACC), which encircles the Antarctic continent and connects all other oceans. The ACC plays a major role in the global heat and freshwater transports and ocean-wide cycles of chemical and biogenic elements, and harbours a series of unique and distinct ecosystems. Due to the upwelling of deep-water masses in the Antarctic Divergence, there is high supply of natural CO2 as well as macronutrients, leading to the worldwide highest surface nutrient concentrations. Despite the ample macronutrients supply, phytoplankton concentration is generally low, limited either by low micronutrient (iron) availability, insufficient light due to deep wind-mixed layers or grazing by zooplankton, or by the combination of all, varying temporally and regionally.

Activity and structure of human acetyl-CoA carboxylase targeted by a specific inhibitor.

PubMed

Jang, SoRi; Gornicki, Piotr; Marjanovic, Jasmina; Bass, Ethan; Lurcotta, Toni; Rodriguez, Pedro; Austin, Jotham; Haselkorn, Robert

2018-05-17

We have studied a series of human acetyl CoA-carboxylase (ACC) 1 and ACC2 proteins with deletions and/or Ser to Ala substitutions of the known phosphorylation sites. In vitro dephosphorylation/phosphorylation experiments reveal a substantial level of phosphorylation of human ACCs produced in insect cells. Our results are consistent with AMPK phosphorylation of Ser 29, Ser 80 , Ser 1,201 and Ser 1,216 . Phosphorylation of the N-terminal regulatory domain decreases ACC1 activity, while phosphorylation of residues in the ACC central domain has no effect. Inhibition of the activity by phosphorylation is significantly more profound at citrate concentrations below 2 mM. Furthermore, deletion of the N-terminal domain facilitates structural changes induced by citrate, including conversion of ACC dimers to linear polymers. We have also identified ACC2 amino acid mutations affecting specific inhibition of the isozyme by compound CD-017-0191. They form two clusters separated by 60-90 Å: one located in the vicinity of the BC active site and the other one in the vicinity of the ACC1 phosphorylation sites in the central domain, suggesting a contribution of the interface of two ACC dimers in the polymer to the inhibitor binding site. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Rostral anterior cingulate cortex morphology predicts treatment response to internet-based CBT for depression

PubMed Central

Webb, Christian A.; Olson, Elizabeth A.; Killgore, William D.S.; Pizzagalli, Diego A.; Rauch, Scott L.; Rosso, Isabelle M.

2018-01-01

Background Rostral and subgenual anterior cingulate cortex (rACC and sgACC) activity and, to a lesser extent, volume have been shown to predict depressive symptom improvement across different antidepressant treatments. This study extends prior work by examining whether rACC and/or sgACC morphology predicts treatment response to internet-based cognitive behavioral therapy (iCBT) for major depressive disorder (MDD). This is the first study to examine neural predictors of response to iCBT. Methods Hierarchical linear modeling tested whether pre-treatment rACC and sgACC volumes predicted depressive symptom improvement during a 6-session (10-week) randomized clinical trial of iCBT (n = 35) vs. a monitored attention control (MAC; n = 38). Analyses also tested whether pre-treatment rACC and sgACC volumes differed between patients who achieved depression remission versus those who did not remit. Results Larger pre-treatment right rACC volume was a significant predictor of greater depressive symptom improvement in iCBT, even when controlling for demographic (age, gender, race) and clinical (baseline depression, anhedonia and anxiety) variables previously linked to treatment response. In addition, pre-treatment right rACC volume was larger among iCBT patients whose depression eventually remitted relative to those who did not remit. Corresponding analyses in the MAC group and for the sgACC were not significant. Conclusions rACC volume prior to iCBT demonstrated incremental predictive validity beyond clinical and demographic variables previously found to predict symptom improvement. Such findings may help inform our understanding of the mediating anatomy of iCBT and, if replicated, may suggest neural targets to augment treatment response (e.g., via modulation of rACC function). ClinicalTrials.gov Identifier NCT01598922 PMID:29486867

Similar outcomes between adenoid cystic carcinoma of the breast and invasive ductal carcinoma: a population-based study from the SEER 18 database.

PubMed

Chen, Qing-Xia; Li, Jun-Jing; Wang, Xiao-Xiao; Lin, Pei-Yang; Zhang, Jie; Song, Chuan-Gui; Shao, Zhi-Ming

2017-01-24

Adenoid cystic carcinoma of the breast (breast-ACC) is a rare and indolent tumor with a good prognosis despite its triple-negative status. However, we observed different outcomes in the present study. Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we enrolled a total of 89,937 eligible patients with an estimated 86 breast-ACC cases and 89,851 invasive ductal carcinoma (IDC) patients. In our study, breast-ACC among women presented with a higher proportion of triple-negative breast cancer (TNBC), which was more likely to feature well-differentiated tumors, rare regional lymph node involvement and greater application of breast-conserving surgery (BCS). Kaplan-Meier analysis revealed that patients with breast-ACC and breast-IDC patients had similar breast cancer-specific survival (BCSS) and overall survival (OS). Moreover, using the propensity score matching method, no significant difference in survival was observed in matched pairs of breast-ACC and breast-IDC patients. Additionally, BCSS and OS did not differ significantly between TNBC-ACC and TNBC-IDC after matching patients for age, tumor size, and nodal status. Further subgroup analysis of molecular subtype indicated improved survival in breast-ACC patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/Her2-) tumors compared to IDC patients with HR+/Her2- tumors. However, the survival of ACC-TNBC and IDC-TNBC patients was similar. In conclusion, ACCs have an indolent clinical course and result in similar outcomes compared to IDC. Understanding these clinical characteristics and outcomes will endow doctors with evidence to provide the same intensive treatment for ACC-TNBC as for IDC-TNBC and lead to more individualized and tailored therapies for breast-ACC patients.

Translational control of human acetyl-CoA carboxylase 1 mRNA is mediated by an internal ribosome entry site in response to ER stress, serum deprivation or hypoxia mimetic CoCl2.

PubMed

Damiano, Fabrizio; Testini, Mariangela; Tocci, Romina; Gnoni, Gabriele V; Siculella, Luisa

2018-04-01

Acetyl-CoA carboxylase 1 (ACC1) is a cytosolic enzyme catalyzing the rate limiting step in de novo fatty acid biosynthesis. There is mounting evidence showing that ACC1 is susceptible to dysregulation and that it is over-expressed in liver diseases associated with lipid accumulation and in several cancers. In the present study, ACC1 regulation at the translational level is reported. Using several experimental approaches, the presence of an internal ribosome entry site (IRES) has been established in the 5' untranslated region (5' UTR) of the ACC1 mRNA. Transfection experiments with the ACC1 5' UTR inserted in a dicistronic reporter vector show a remarkable increase in the downstream cistron translation, through a cap-independent mechanism. The endoplasmic reticulum (ER) stress condition and the related unfolded protein response (UPR), triggered by treatment with thapsigargin and tunicamycin, cause an increase of the cap-independent translation of ACC1 mRNA in HepG2 cells, despite the overall reduction in global protein synthesis. Other stress conditions, such as serum starvation and incubation with hypoxia mimetic agent CoCl 2 , up-regulate ACC1 expression in HepG2 cells at the translational level. Overall, these findings indicate that the presence of an IRES in the ACC1 5' UTR allows ACC1 mRNA translation in conditions that are inhibitory to cap-dependent translation. A potential involvement of the cap-independent translation of ACC1 in several pathologies, such as obesity and cancer, has been discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

Anticipatory activity in anterior cingulate cortex can be independent of conflict and error likelihood.

PubMed

Aarts, Esther; Roelofs, Ardi; van Turennout, Miranda

2008-04-30

Previous studies have found no agreement on whether anticipatory activity in the anterior cingulate cortex (ACC) reflects upcoming conflict, error likelihood, or actual control adjustments. Using event-related functional magnetic resonance imaging, we investigated the nature of preparatory activity in the ACC. Informative cues told the participants whether an upcoming target would or would not involve conflict in a Stroop-like task. Uninformative cues provided no such information. Behavioral responses were faster after informative than after uninformative cues, indicating cue-based adjustments in control. ACC activity was larger after informative than uninformative cues, as would be expected if the ACC is involved in anticipatory control. Importantly, this activation in the ACC was observed for informative cues even when the information conveyed by the cue was that the upcoming target evokes no response conflict and has low error likelihood. This finding demonstrates that the ACC is involved in anticipatory control processes independent of upcoming response conflict or error likelihood. Moreover, the response of the ACC to the target stimuli was critically dependent on whether the cue was informative or not. ACC activity differed among target conditions after uninformative cues only, indicating ACC involvement in actual control adjustments. Together, these findings argue strongly for a role of the ACC in anticipatory control independent of anticipated conflict and error likelihood, and also show that such control can eliminate conflict-related ACC activity during target processing. Models of frontal cortex conflict-detection and conflict-resolution mechanisms require modification to include consideration of these anticipatory control properties of the ACC.

Contraction-induced changes in acetyl-CoA carboxylase and 5'-AMP-activated kinase in skeletal muscle.

PubMed

Vavvas, D; Apazidis, A; Saha, A K; Gamble, J; Patel, A; Kemp, B E; Witters, L A; Ruderman, N B

1997-05-16

The concentration of malonyl-CoA, a negative regulator of fatty acid oxidation, diminishes acutely in contracting skeletal muscle. To determine how this occurs, the activity and properties of acetyl-CoA carboxylase beta (ACC-beta), the skeletal muscle isozyme that catalyzes malonyl-CoA formation, were examined in rat gastrocnemius-soleus muscles at rest and during contractions induced by electrical stimulation of the sciatic nerve. To avoid the problem of contamination of the muscle extract by mitochondrial carboxylases, an assay was developed in which ACC-beta was first purified by immunoprecipitation with a monoclonal antibody. ACC-beta was quantitatively recovered in the immunopellet and exhibited a high sensitivity to citrate (12-fold activation) and a Km for acetyl-CoA (120 microM) similar to that reported for ACC-beta purified by other means. After 5 min of contraction, ACC-beta activity was decreased by 90% despite an apparent increase in the cytosolic concentration of citrate, a positive regulator of ACC. SDS-polyacrylamide gel electrophoresis of both homogenates and immunopellets from these muscles showed a decrease in the electrophoretic mobility of ACC, suggesting that phosphorylation could account for the decrease in ACC activity. In keeping with this notion, citrate activation of ACC purified from contracting muscle was markedly depressed. In addition, homogenization of the muscles in a buffer free of phosphatase inhibitors and containing the phosphatase activators glutamate and MgCl2 or treatment of immunoprecipitated ACC-beta with purified protein phosphatase 2A abolished the decreases in both ACC-beta activity and electrophoretic mobility caused by contraction. The rapid decrease in ACC-beta activity after the onset of contractions (50% by 20 s) and its slow restoration to initial values during recovery (60-90 min) were paralleled temporally by reciprocal changes in the activity of the alpha2 but not the alpha1 isoform of 5'-AMP-activated protein kinase (AMPK). In conclusion, the results suggest that the decrease in ACC activity during muscle contraction is caused by an increase in its phosphorylation, most probably due, at least in part, to activation of the alpha2 isoform of AMPK. They also suggest a dual mechanism for ACC regulation in muscle in which inhibition by phosphorylation takes precedence over activation by citrate. These alterations in ACC and AMPK activity, by diminishing the concentration of malonyl-CoA, could be responsible for the increase in fatty acid oxidation observed in skeletal muscle during exercise.

Liver resection for metastases of tracheal adenoid cystic carcinoma: Report of two cases.

PubMed

Hashimoto, Shintaro; Sumida, Yorihisa; Tobinaga, Shuichi; Wada, Hideo; Wakata, Kouki; Nonaka, Takashi; Kunizaki, Masaki; Hidaka, Shigekazu; Kinoshita, Naoe; Sawai, Terumitsu; Nagayasu, Takeshi

2018-05-16

Tracheal adenoid cystic carcinoma (ACC) is rare and accounts for <1% of all lung cancers. Although ACC is classified as a low-grade tumor, metastases are frequently identified in the late period. Extrapulmonary metastases are rare, and their resection has rarely been reported. Case 1: A 77-year-old man underwent tracheal resection for ACC with postoperative radiation (60 Gy) 14 years before　(at the age of 63). He underwent two subsequent pulmonary resections for metastases. Fourteen years after the first operation, he underwent extended right posterior segmentectomy with resection of segment IV and radiofrequency ablation for metastases of ACC to the liver. He was diagnosed with metastases to the kidney with peritoneal dissemination 4 years after the liver resection and died of pneumonia 2 years later. Case 2: A 53-year-old woman underwent a two-stage operation involving tracheal resection for ACC and partial resection of liver segments II and V for metastases of ACC to the liver. The tracheal margin was histopathologically positive. Postoperative radiation was performed, and she was tumor-free for 10 months after the liver resection. Complete resection of tracheal ACC provides better survival. Radiotherapy is also recommended. However, the optimal treatment for metastases of ACC is unclear, especially because liver resection for metastases of tracheal ACC is rarely reported. Our two cases of metastases of tracheal ACC were surgically managed with good outcomes. Liver resection for metastases of tracheal ACC may contribute to long survival. Copyright © 2018. Published by Elsevier Ltd.

Comparison of the Surgical Outcomes of Dorsal Augmentation Using Expanded Polytetrafluoroethylene or Autologous Costal Cartilage.

PubMed

Joo, Yeon Hee; Jang, Yong Ju

2016-09-01

Dorsal augmentation material includes alloplastic implants and autologous tissues. However, there has been no comparison to date of dorsal augmentation using different materials performed by the same surgeon. To compare the aesthetic outcomes and complications of dorsal augmentation using expanded polytetrafluoroethylene (ePTFE) and autologous costal cartilage (ACC) in rhinoplasty. A retrospective review of the medical records of 244 patients who underwent dorsal augmentation performed by the same surgeon at the Asan Medical Center using ePTFE or ACC from March 1, 2003, through September 31, 2015. Patient demographics and surgical procedures were analyzed. The aesthetic outcomes were scored from 1 (worst) to 4 (best) by 3 otolaryngologists. Changes in dorsal height and radix height were measured by comparing preoperative and postoperative profile views. Postoperative complications were also evaluated. A total of 244 patients who underwent augmentation rhinoplasty were reviewed in this study, including 141 men (57.8%) and 103 women (42.2%). The ePTFE group included 176 patients, and the ACC group comprised 68 patients. In the ePTFE and ACC groups, 96 patients (54.5%) and 45 patients (66.2%) were male, respectively. The patient ages ranged from 11 to 69 years, with a mean (SD) age of 30.3 (11.49) years in the ePTFE group and 36.04 (12.65) years in the ACC group. The mean (SD) aesthetic outcome scores were comparable between the 2 groups: 2.99 (0.05) in the ePTFE group and 2.99 (0.06) in the ACC group (P = .93). The change of dorsal (2.64% in ePTFE group and 5.82% in ACC group) and radix (3.62% in ePTFE group and 3.77% in ACC group) heights were significantly increased after augmentation in both groups (P < .001) even though the dorsal height of the ACC group after augmentation showed a significantly greater increase compared to the ePTFE group (P < .001). However, the complication rate was significantly higher in the ACC group: 4.0% in ePTFE group and 11.8% in ACC group (P = .02). Dorsal augmentation with ACC produces similar aesthetic outcomes but a higher complication rate than dorsal augmentation with ePTFE. This higher complication rate may justify the use of ePTFE implants for dorsal augmentation in Asian patients undergoing rhinoplasty. 3.

Molecular cloning and characterization of two genes for the biotin carboxylase and carboxyltransferase subunits of acetyl coenzyme A carboxylase in Myxococcus xanthus.

PubMed

Kimura, Y; Miyake, R; Tokumasu, Y; Sato, M

2000-10-01

We have cloned a DNA fragment from a genomic library of Myxococcus xanthus using an oligonucleotide probe representing conserved regions of biotin carboxylase subunits of acetyl coenzyme A (acetyl-CoA) carboxylases. The fragment contained two open reading frames (ORF1 and ORF2), designated the accB and accA genes, capable of encoding a 538-amino-acid protein of 58.1 kDa and a 573-amino-acid protein of 61.5 kDa, respectively. The protein (AccA) encoded by the accA gene was strikingly similar to biotin carboxylase subunits of acetyl-CoA and propionyl-CoA carboxylases and of pyruvate carboxylase. The putative motifs for ATP binding, CO(2) fixation, and biotin binding were found in AccA. The accB gene was located upstream of the accA gene, and they formed a two-gene operon. The protein (AccB) encoded by the accB gene showed high degrees of sequence similarity with carboxyltransferase subunits of acetyl-CoA and propionyl-CoA carboxylases and of methylmalonyl-CoA decarboxylase. Carboxybiotin-binding and acyl-CoA-binding domains, which are conserved in several carboxyltransferase subunits of acyl-CoA carboxylases, were found in AccB. An accA disruption mutant showed a reduced growth rate and reduced acetyl-CoA carboxylase activity compared with the wild-type strain. Western blot analysis indicated that the product of the accA gene was a biotinylated protein that was expressed during the exponential growth phase. Based on these results, we propose that this M. xanthus acetyl-CoA carboxylase consists of two subunits, which are encoded by the accB and accA genes, and occupies a position between prokaryotic and eukaryotic acetyl-CoA carboxylases in terms of evolution.

Reduced heart size and increased myocardial fuel substrate oxidation in ACC2 mutant mice

PubMed Central

Essop, M. Faadiel; Camp, Heidi S.; Choi, Cheol Soo; Sharma, Saumya; Fryer, Ryan M.; Reinhart, Glenn A.; Guthrie, Patrick H.; Bentebibel, Assia; Gu, Zeiwei; Shulman, Gerald I.; Taegtmeyer, Heinrich; Wakil, Salih J.; Abu-Elheiga, Lutfi

2008-01-01

The cardiac-enriched isoform of acetyl-CoA carboxylase (ACC2) is a key regulator of mitochondrial fatty acid (FA) uptake via carnitine palmitoyltransferase 1 (CPT1). To test the hypothesis that oxidative metabolism is upregulated in hearts from animals lacking ACC2 (employing a transgenic Acc2-mutant mouse), we assessed cardiac function in vivo and determined rates of myocardial substrate oxidation ex vivo. When examined by echocardiography, there was no difference in systolic function, but left ventricular mass of the Acc2-mutant (MUT) mouse was significantly reduced (∼25%) compared with wild-types (WT). Reduced activation of the mammalian target of rapamycin (mTOR) and its downstream target p70S6K was found in MUT hearts. Exogenous oxidation rates of oleate were increased ∼22%, and, unexpectedly, exogenous glucose oxidation rates were also increased in MUT hearts. Using a hyperinsulinemic-euglycemic clamp, we found that glucose uptake in MUT hearts was increased by ∼83%. Myocardial triglyceride levels were significantly reduced in MUT vs. WT while glycogen content was the same. In parallel, transcript levels of PPARα and its target genes, pyruvate dehydrogenase kinase-4 (PDK-4), malonyl-CoA decarboxylase (MCD), and mCPT1, were downregulated in MUT mice. In summary, we report that 1) Acc2-mutant hearts exhibit a marked preference for the oxidation of both glucose and FAs coupled with greater utilization of endogenous fuel substrates (triglycerides), 2) attenuated mTOR signaling may result in reduced heart sizes observed in Acc2-mutant mice, and 3) Acc2-mutant hearts displayed normal functional parameters despite a significant decrease in size. PMID:18487439

High expression of Polycomb group protein EZH2 predicts poor survival in salivary gland adenoid cystic carcinoma.

PubMed

Vékony, H; Raaphorst, F M; Otte, A P; van Lohuizen, M; Leemans, C R; van der Waal, I; Bloemena, E

2008-06-01

The prognosis of adenoid cystic carcinoma (ACC), a malignant salivary gland tumour, depends on clinicopathological parameters. To decipher the biological behaviour of ACC, and to identify patients at risk of developing metastases, additional markers are needed. Expression of the cell cycle proteins p53, cyclin D1, p16(INK4a), E2F1 and Ki-67, together with the Polycomb group (PcG) proteins BMI-1, MEL-18, EZH2 and EED was investigated immunohistochemically 21 formalin-fixed, paraffin-embedded primary ACCs in relation to tumour characteristics. ACC revealed significantly increased expression of the cell cycle proteins compared to normal salivary tissue (n = 17). Members of the two PcG complexes displayed mutually exclusive expression in normal salivary gland tissue, with BMI-1 and MEL-18 being abundantly present. In ACC, this expression pattern was disturbed, with EZH2 and EED showing significantly increased expression levels. In univariate analysis, presence of recurrence, poor differentiation and high EZH2 levels (>25% immunopositivity) significantly correlated with unfavourable outcome. ACCs with high proliferative rate (>25% Ki-67 immunopositivity) significantly correlated with high levels of EZH2 and p16. Only the development of recurrence was an independent prognostic factor of survival in multivariate analysis. Expression of PcG complexes and of essential cell cycle proteins is highly deregulated in ACC. Also, EZH2 expression has prognostic relevance in this malignancy.

Neural correlates of appetitive extinction in humans

PubMed Central

Tapia León, Isabell; Stark, Rudolf; Klucken, Tim

2017-01-01

Abstract Appetitive extinction receives attention as an important model for the treatment of psychiatric disorders. However, in humans, its underlying neural correlates remain unknown. To close this gap, we investigated appetitive acquisition and extinction with fMRI in a 2-day monetary incentive delay paradigm. During appetitive conditioning, one stimulus (CS+) was paired with monetary reward, while another stimulus (CS−) was never rewarded. Twenty-four hours later, subjects underwent extinction, in which neither CS was reinforced. Appetitive conditioning elicited stronger skin conductance responses to the CS+ as compared with the CS−. Regarding subjective ratings, the CS+ was rated more pleasant and arousing than the CS− after conditioning. Furthermore, fMRI-results (CS+ − CS−) showed activation of the reward circuitry including amygdala, midbrain and striatal areas. During extinction, conditioned responses were successfully extinguished. In the early phase of extinction, we found a significant activation of the caudate, the hippocampus, the dorsal and ventral anterior cingulate cortex (dACC and vACC). In the late phase, we found significant activation of the nucleus accumbens (NAcc) and the amygdala. Correlational analyses with subjective ratings linked extinction success to the vACC and the NAcc, while associating the dACC with reduced extinction. The results reveal neural correlates of appetitive extinction in humans and extend assumptions from models for human extinction learning. PMID:27803289

A Public-Private Partnership Develops and Externally Validates a 30-Day Hospital Readmission Risk Prediction Model

PubMed Central

Choudhry, Shahid A.; Li, Jing; Davis, Darcy; Erdmann, Cole; Sikka, Rishi; Sutariya, Bharat

2013-01-01

Introduction: Preventing the occurrence of hospital readmissions is needed to improve quality of care and foster population health across the care continuum. Hospitals are being held accountable for improving transitions of care to avert unnecessary readmissions. Advocate Health Care in Chicago and Cerner (ACC) collaborated to develop all-cause, 30-day hospital readmission risk prediction models to identify patients that need interventional resources. Ideally, prediction models should encompass several qualities: they should have high predictive ability; use reliable and clinically relevant data; use vigorous performance metrics to assess the models; be validated in populations where they are applied; and be scalable in heterogeneous populations. However, a systematic review of prediction models for hospital readmission risk determined that most performed poorly (average C-statistic of 0.66) and efforts to improve their performance are needed for widespread usage. Methods: The ACC team incorporated electronic health record data, utilized a mixed-method approach to evaluate risk factors, and externally validated their prediction models for generalizability. Inclusion and exclusion criteria were applied on the patient cohort and then split for derivation and internal validation. Stepwise logistic regression was performed to develop two predictive models: one for admission and one for discharge. The prediction models were assessed for discrimination ability, calibration, overall performance, and then externally validated. Results: The ACC Admission and Discharge Models demonstrated modest discrimination ability during derivation, internal and external validation post-recalibration (C-statistic of 0.76 and 0.78, respectively), and reasonable model fit during external validation for utility in heterogeneous populations. Conclusions: The ACC Admission and Discharge Models embody the design qualities of ideal prediction models. The ACC plans to continue its partnership to further improve and develop valuable clinical models. PMID:24224068

Determination of 1-aminocyclopropane-1-carboxylic acid in apple extracts by capillary electrophoresis with laser-induced fluorescence detection.

PubMed

Liu, Xin; Li, Dian-Fan; Wang, Yun; Lu, Ying-Tang

2004-12-17

A rapid and sensitive method for the determination of 1-aminocyclopropane-1-carboxylic acid (ACC) in apple tissues has been described. This method is based on the derivatization of ACC with 3-(2-furoyl)quinoline-2-carboxaldehyde (FQ), and separation and quantification of the resulting FQ-ACC derivative by capillary electrophoresis coupled to laser-induced fluorescence detection (CE-LIF). Our results indicated that ACC derivatized with FQ could be well separated from other interfering amino acids using 20 mM borate buffer (pH 9.35) containing 40 mM sodium dodecyl sulfate and 10 mM Brij 35. The linearity of ACC was determined in the range from 0.05 to 5 microM with a correlation of 0.9967. The concentration detection limit for ACC was 10 nM (signal-to-noise = 3). The sensitivity and selectivity of this described method allows the analysis of ACC in crude apple extracts without extra purification and enrichment procedure.

Carbonate mineralization via an amorphous calcium carbonate (ACC) pathway: Tuning polymorph selection by Mg, pH, and mixing environment

NASA Astrophysics Data System (ADS)

Dove, P. M.; Blue, C.; Mergelsberg, S. T.; Giuffre, A. J.; Han, N.; De Yoreo, J. J.

2017-12-01

Mineral formation by nonclassical processes is widespread with many pathways that include aggregation of nanoparticles, oriented attachment of fully formed crystals, and sequential nucleation/transformation of amorphous phases (De Yoreo et al., 2015, Science). Field observations indicate amorphous calcium carbonate (ACC) can be the initial precipitate when local conditions promote high supersaturations for short time periods. Examples include microbial mats, marine porewaters that undergo pulses of increased alkalinity, closed basin lakes, and sabkhas. The crystalline products exhibit diverse morphologies and complex elemental and isotopic signatures. This study quantifies relationships between solution composition and the crystalline polymorphs that transform from ACC (Blue et al., GCA, 2017). Our experimental design synthesized ACC under controlled conditions for a suite of compositions by tuning input pH, Mg/Ca, and total carbonate concentration. ACC products were allowed to transform within output suspensions under stirred or quiescent mixing while characterizing the polymorph and composition of evolving solutions and solids. We find that ACC transforms to crystalline polymorphs with a systematic relationship to solution composition to give a quantitative framework based upon solution aMg2+/aCa2+ and aCO32-/aCa2+. We also measure a polymorph-specific evolution of pH and Mg/Ca during the transformation that indicates the initial polymorph to form. Pathway is further modulated by stirring versus quiescent conditions. The findings reconcile discrepancies among previous studies of ACC to crystalline products and supports claims that monohydrocalcite may be an overlooked, transient phase during formation of some aragonite and calcite deposits. Organic additives and extreme pH are not required to tune composition and polymorph. Insights from this study reiterate the need to revisit long-standing dogmas regarding controls on CaCO3 polymorph selection. Classical models assume thermodynamic equilibria but cannot provide a reliable predictor of compositions when kinetic factors are driving mineralization. Nonclassical pathways to mineralization may be the missing link to interpreting unusual CaCO3 polymorphs, compositions and textures in modern and ancient carbonates.

Dehydration-induced amorphous phases of calcium carbonate.

PubMed

Saharay, Moumita; Yazaydin, A Ozgur; Kirkpatrick, R James

2013-03-28

Amorphous calcium carbonate (ACC) is a critical transient phase in the inorganic precipitation of CaCO3 and in biomineralization. The calcium carbonate crystallization pathway is thought to involve dehydration of more hydrated ACC to less hydrated ACC followed by the formation of anhydrous ACC. We present here computational studies of the transition of a hydrated ACC with a H2O/CaCO3 ratio of 1.0 to anhydrous ACC. During dehydration, ACC undergoes reorganization to a more ordered structure with a significant increase in density. The computed density of anhydrous ACC is similar to that of calcite, the stable crystalline phase. Compared to the crystalline CaCO3 phases, calcite, vaterite, and aragonite, the computed local structure of anhydrous ACC is most-similar to those of calcite and vaterite, but the overall structure is not well described by either. The strong hydrogen bond interaction between the carbonate ions and water molecules plays a crucial role in stabilizing the less hydrated ACC compositions compared to the more hydrated ones, leading to a progressively increasing hydration energy with decreasing water content.

Transformation and crystallization energetics of synthetic and biogenic amorphous calcium carbonate.

PubMed

Radha, A V; Forbes, Tori Z; Killian, Christopher E; Gilbert, P U P A; Navrotsky, Alexandra

2010-09-21

Amorphous calcium carbonate (ACC) is a metastable phase often observed during low temperature inorganic synthesis and biomineralization. ACC transforms with aging or heating into a less hydrated form, and with time crystallizes to calcite or aragonite. The energetics of transformation and crystallization of synthetic and biogenic (extracted from California purple sea urchin larval spicules, Strongylocentrotus purpuratus) ACC were studied using isothermal acid solution calorimetry and differential scanning calorimetry. Transformation and crystallization of ACC can follow an energetically downhill sequence: more metastable hydrated ACC → less metastable hydrated ACC ⇒ anhydrous ACC ∼ biogenic anhydrous ACC ⇒ vaterite → aragonite → calcite. In a given reaction sequence, not all these phases need to occur. The transformations involve a series of ordering, dehydration, and crystallization processes, each lowering the enthalpy (and free energy) of the system, with crystallization of the dehydrated amorphous material lowering the enthalpy the most. ACC is much more metastable with respect to calcite than the crystalline polymorphs vaterite or aragonite. The anhydrous ACC is less metastable than the hydrated, implying that the structural reorganization during dehydration is exothermic and irreversible. Dehydrated synthetic and anhydrous biogenic ACC are similar in enthalpy. The transformation sequence observed in biomineralization could be mainly energetically driven; the first phase deposited is hydrated ACC, which then converts to anhydrous ACC, and finally crystallizes to calcite. The initial formation of ACC may be a first step in the precipitation of calcite under a wide variety of conditions, including geological CO(2) sequestration.

Elevated Glutamatergic Compounds in Pregenual Anterior Cingulate in Pediatric Autism Spectrum Disorder Demonstrated by 1H MRS and 1H MRSI

PubMed Central

Bejjani, Anthony; O'Neill, Joseph; Kim, John A.; Frew, Andrew J.; Yee, Victor W.; Ly, Ronald; Kitchen, Christina; Salamon, Noriko; McCracken, James T.; Toga, Arthur W.; Alger, Jeffry R.; Levitt, Jennifer G.

2012-01-01

Recent research in autism spectrum disorder (ASD) has aroused interest in anterior cingulate cortex and in the neurometabolite glutamate. We report two studies of pregenual anterior cingulate cortex (pACC) in pediatric ASD. First, we acquired in vivo single-voxel proton magnetic resonance spectroscopy (1H MRS) in 8 children with ASD and 10 typically developing controls who were well matched for age, but with fewer males and higher IQ. In the ASD group in midline pACC, we found mean 17.7% elevation of glutamate + glutamine (Glx) (p<0.05) and 21.2% (p<0.001) decrement in creatine + phosphocreatine (Cr). We then performed a larger (26 subjects with ASD, 16 controls) follow-up study in samples now matched for age, gender, and IQ using proton magnetic resonance spectroscopic imaging (1H MRSI). Higher spatial resolution enabled bilateral pACC acquisition. Significant effects were restricted to right pACC where Glx (9.5%, p<0.05), Cr (6.7%, p<0.05), and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (10.2%, p<0.01) in the ASD sample were elevated above control. These two independent studies suggest hyperglutamatergia and other neurometabolic abnormalities in pACC in ASD, with possible right-lateralization. The hyperglutamatergic state may reflect an imbalance of excitation over inhibition in the brain as proposed in recent neurodevelopmental models of ASD. PMID:22848344

Expression, purification, and characterization of human acetyl-CoA carboxylase 2.

PubMed

Kim, Ki Won; Yamane, Harvey; Zondlo, James; Busby, James; Wang, Minghan

2007-05-01

The full-length human acetyl-CoA carboxylase 1 (ACC1) was expressed and purified to homogeneity by two separate groups (Y.G. Gu, M. Weitzberg, R.F. Clark, X. Xu, Q. Li, T. Zhang, T.M. Hansen, G. Liu, Z. Xin, X. Wang, T. McNally, H. Camp, B.A. Beutel, H.I. Sham, Synthesis and structure-activity relationships of N-{3-[2-(4-alkoxyphenoxy)thiazol-5-yl]-1-methylprop-2-ynyl}carboxy derivatives as selective acetyl-CoA carboxylase 2 inhibitors, J. Med. Chem. 49 (2006) 3770-3773; D. Cheng, C.H. Chu, L. Chen, J.N. Feder, G.A. Mintier, Y. Wu, J.W. Cook, M.R. Harpel, G.A. Locke, Y. An, J.K. Tamura, Expression, purification, and characterization of human and rat acetyl coenzyme A carboxylase (ACC) isozymes, Protein Expr. Purif., in press). However, neither group was successful in expressing the full-length ACC2 due to issues of solubility and expression levels. The two versions of recombinant human ACC2 in these reports are either truncated (lacking 1-148 aa) or have the N-terminal 275 aa replaced with the corresponding ACC1 region (1-133 aa). Despite the fact that ACC activity was observed in both cases, these constructs are not ideal because the N-terminal region of ACC2 could be important for the correct folding of the catalytic domains. Here, we report the high level expression and purification of full-length human ACC2 that lacks only the N-terminal membrane attachment sequence (1-20 and 1-26 aa, respectively) in Trichoplusia ni cells. In addition, we developed a sensitive HPLC assay to analyze the kinetic parameters of the recombinant enzyme. The recombinant enzyme is a soluble protein and has a K(m) value of 2 microM for acetyl-CoA, almost 30-fold lower than that reported for the truncated human ACC2. Our recombinant enzyme also has a lower K(m) value for ATP (K(m)=52 microM). Although this difference could be ascribed to different assay conditions, our data suggest that the longer human ACC2 produced in our system may have higher affinities for the substrates and could be more similar to the native enzyme.

Activation of acetyl-coenzyme A carboxylase is involved in Taxol-induced ovarian cancer cell death

PubMed Central

WU, JIANG; JI, FANG; DI, WEN; CHEN, HONGDUO; WAN, YINSHENG

2011-01-01

Acetyl-coenzyme A carboxylase (ACC) is an attractive target for research into the treatment of a variety of human diseases, including diabetes, obesity and cancer. Mounting evidence suggests that the inhibition of ACC induced of cancer cell apoptosis. However, whether the inhibition of ACC regulates apoptosis in CaOV3 cancer cells has yet to be addressed. This study investigated the cytotoxic mechanism of action of ACC inhibition. Results showed that 5-(tetradecyloxy)-2-furoic acid (TOFA), an ACC inhibitor, enhanced Taxol-induced CaOV3 human ovarian cancer cell apoptosis. Notably, when TOFA was administered as a monotherapy, it induced CaOV3 cell apoptosis. Pre-treatment with the EGFR inhibitor PD153035 was found to markedly enhance ACC phosphorylation, whereas AMP-activated protein kinase (AMPK) activator AICAR was found to marginally enhance ACC phosphorylation. Taken together, the data showed ACC is a potential novel molecular target of Taxol. Additionally, ACC inhibition partially contributed to the cytotoxic effect of Taxol in ovarian cancer cells. PMID:22866118

Activation of acetyl-coenzyme A carboxylase is involved in Taxol-induced ovarian cancer cell death.

PubMed

Wu, Jiang; Ji, Fang; DI, Wen; Chen, Hongduo; Wan, Yinsheng

2011-05-01

Acetyl-coenzyme A carboxylase (ACC) is an attractive target for research into the treatment of a variety of human diseases, including diabetes, obesity and cancer. Mounting evidence suggests that the inhibition of ACC induced of cancer cell apoptosis. However, whether the inhibition of ACC regulates apoptosis in CaOV3 cancer cells has yet to be addressed. This study investigated the cytotoxic mechanism of action of ACC inhibition. Results showed that 5-(tetradecyloxy)-2-furoic acid (TOFA), an ACC inhibitor, enhanced Taxol-induced CaOV3 human ovarian cancer cell apoptosis. Notably, when TOFA was administered as a monotherapy, it induced CaOV3 cell apoptosis. Pre-treatment with the EGFR inhibitor PD153035 was found to markedly enhance ACC phosphorylation, whereas AMP-activated protein kinase (AMPK) activator AICAR was found to marginally enhance ACC phosphorylation. Taken together, the data showed ACC is a potential novel molecular target of Taxol. Additionally, ACC inhibition partially contributed to the cytotoxic effect of Taxol in ovarian cancer cells.

The ACC strategy in biomineralization: the case of earthworm's amorphous spherulites

NASA Astrophysics Data System (ADS)

Briones, Maria J. I.; Alvarez-Otero, Rosa; Méndez, Jesús; Gago Duport, Luis

2010-05-01

The occurrence of amorphous calcium carbonate (ACC), an hydrated and highly soluble form of solid CaCO3, seems to be a common feature in all carbonate forming organisms such as mollusks, corals, echinoderms and crustaceans. The ubiquity of ACC in these Ca-carbonate biomineralizing systems, as a precursor of further crystalline phases, has recently open the interesting question about if the formation of an amorphous phase is a necessary step in the calcification process of all organisms and consequently, whether it would be possible to define the "amorphous precursor estategy" as a general mechanism in biomineralization. Neverthelees, although ACC appears to be widespread in these organisms very little is known about its particular role in the biomineralization scheme of the different phyla. The formation of CaCO3 spherulites in the calciferous glands of earthworms is a particular case of calcareous biomineralization involving the presence of ACC as a transient precursor phase [2]. Interestingly, the formation of crystalline carbonates via ACC in these organisms is not connected with skeleton building so it must play another functional role. In addition, the transient transformation stages can be followed by in situ spectrometric techniques and therefore, earthworms provide and adequate model to analyse the mutual interactions between ACC-solvent-and crystalline phases. In this study, we have analysed the morphological and structural transformations from the initial ACC spherulites until the formation of the crystalline phases: vaterite (and/or aragonite) and finally calcite, is accomplished. The characterization of ACC was done by performing in situ FT-IR, together with and HREM and Debye scherrer -XRD. The structural results were interpreted in the light of the histological study of the gland. The geometry of the secretory epithelium of the calciferous gland, as evidenced by TEM [2], shows the presence of irregulary shaped cells with their apical surface consisting of dendritic indentations and club-shaped expansions extending to the inter-lamella spaces. The cell basal area is extremely folded and contains abundant mitochondria and membranous infoldings. This morphology could provide the explanatory mechanism by which the calcium present in the blood enters into the gland. Furthermore, the presence of spherulites in the interlamellar space and wrapped by an organic matrix suggest that the calcification process is under organic control. Further information of the intermediate transformation stages in the ACC spherultiths was provided by the FE-SEM analysis. That shown the collapse of the internal structure of spherulits into radially distributed regions associated with the organic matrix. As ACC is a highly soluble form of CaCO3 that includes a water molecule in the structure, its transformation to one of the crystalline polymorphs, would necessarily involve the release of H2O and the Ca+2 ion. As a result of this, a gradual decrease in volume at the inner part of the spherulites is observed. Taken these findings together, we conclude that the transformation of the initially stabilised ACC occurs via a ‘source-sink mechanism'. Accordingly, the uptake of Ca by the cells (sink) causes a decrease in the [Ca+2] of the extracellular fluid. This, in turn, will induce the dissolution of the spherulites (source), with the subsequent release of H2O and Ca+2 so that the Ca activity in the extracellular fluid is maintained. As result of this process, while the concentrations of ACC become unsaturated, both vaterite and calcite are still supersaturated and crystallization can be then initiated via an heterogeneous nucleation mechanism at the spherulite surfaces. This mechanism can be used by the orgnism as an efficient way to control the concentration of Ca+2 in the extracellular fluid within its physiological range. References [1] Gago-Duport, L., Briones, M.J.I., Rodriguez, J.B., Covelo, B. (2008) J. Struct Biol, 162: 422-35. [2] Mendez J., Rodriguez, J.B., Alvarez-Otero, R., Briones M.J.I., Gago-Duport, L. Microsc Microanal 15 (supp 3): 25-26 (2009) DOI 10.1017/S1431927609990584

Ketamine differentially restores diverse alterations of neuroligins in brain regions in a rat model of neuropathic pain-induced depression.

PubMed

Pan, Wei; Zhang, Guang-Fen; Li, Hui-Hui; Ji, Mu-Huo; Zhou, Zhi-Qiang; Li, Kuan-Yu; Yang, Jian-Jun

2018-07-04

Depression is present in a large proportion of patients suffering from chronic pain, and yet the underlying mechanisms remain to be elucidated. Neuroligins (NLs), as a family of cell-adhesion proteins, are involved in synaptic formation and have been linked to various neuropsychiatric disorders. Here, we studied the alterations in NL1 and NL2 in the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), and the hippocampus in a rat model of neuropathic pain-induced depression, and whether ketamine, a rapid and robust antidepressant, could restore these abnormalities. In the present study, we found that spared nerve injury induced significant mechanical allodynia and subsequent depressive-like symptoms, along with decreased NL1 and increased NL2 in the mPFC, decreased NL1 in the ACC, and decreased NL2 in the hippocampus. In addition, brain-derived neurotrophic factor (BDNF) was reduced in these brain regions. It is noteworthy that ketamine (10 mg/kg) relieved neuropathic pain-induced depressive behaviors and restored alterations of BDNF and NLs in the mPFC and the hippocampus at 24 h and 72 h after the administration of ketamine, but only restored BDNF in the ACC. In conclusion, NLs showed diverse changes in different brain regions in the rat model of neuropathic pain-induced depression, which could be reversed differentially by the administration of ketamine.

Evaluating the safety impact of adaptive cruise control in traffic oscillations on freeways.

PubMed

Li, Ye; Li, Zhibin; Wang, Hao; Wang, Wei; Xing, Lu

2017-07-01

Adaptive cruise control (ACC) has been considered one of the critical components of automated driving. ACC adjusts vehicle speeds automatically by measuring the status of the ego-vehicle and leading vehicle. Current commercial ACCs are designed to be comfortable and convenient driving systems. Little attention is paid to the safety impacts of ACC, especially in traffic oscillations when crash risks are the highest. The primary objective of this study was to evaluate the impacts of ACC parameter settings on rear-end collisions on freeways. First, the occurrence of a rear-end collision in a stop-and-go wave was analyzed. A car-following model in an integrated ACC was developed for a simulation analysis. The time-to-collision based factors were calculated as surrogate safety measures of the collision risk. We also evaluated different market penetration rates considering that the application of ACC will be a gradual process. The results showed that the safety impacts of ACC were largely affected by the parameters. Smaller time delays and larger time gaps improved safety performance, but inappropriate parameter settings increased the collision risks and caused traffic disturbances. A higher reduction of the collision risk was achieved as the ACC vehicle penetration rate increased, especially in the initial stage with penetration rates of less than 30%. This study also showed that in the initial stage, the combination of ACC and a variable speed limit achieved better safety improvements on congested freeways than each single technique. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antibody-containing cell response in lymph of sheep after intra-intestinal infusion of ovalbumin with and without DEAE-dextran.

PubMed Central

Beh, K J

1979-01-01

The output of antibody-containing cells (ACC) was monitored in efferent ileal lymph after continuous infusion of ovalbumin into the ileum of sheep with and without the adjuvant DEAE-dextran. When ovalbumin was infused at the slow rate of 5 ml/h, maximum outputs of 2.9 x 10(5) and 2.4 x 10(5 ACC/h were observed on days 9 and 16 respectively. When infused at the faster rate of 15 ml/h, peak levels of 6.9 x 10(5) and 11.7 x 10(5) ACC/h were recorded on days 10 and 16 respectively. The maximum response was substantially enhanced when ovalbumin was infused simultaneously with DEAE-dextran when a mean output of 51.7 x 10(5) ACC/h occurred on day 10. With all treatments the distribution of ACC amongst various immunoglobulin classes was similar. During the first few days of the response IgM-specific ACC predominated and later IgG1-specific ACC were most abundant. Throughout the response a substantial proportion (10-81%) of ACC in efferent ileal lymph were IgA-specific. PMID:572818

AtomicChargeCalculator: interactive web-based calculation of atomic charges in large biomolecular complexes and drug-like molecules.

PubMed

Ionescu, Crina-Maria; Sehnal, David; Falginella, Francesco L; Pant, Purbaj; Pravda, Lukáš; Bouchal, Tomáš; Svobodová Vařeková, Radka; Geidl, Stanislav; Koča, Jaroslav

2015-01-01

Partial atomic charges are a well-established concept, useful in understanding and modeling the chemical behavior of molecules, from simple compounds, to large biomolecular complexes with many reactive sites. This paper introduces AtomicChargeCalculator (ACC), a web-based application for the calculation and analysis of atomic charges which respond to changes in molecular conformation and chemical environment. ACC relies on an empirical method to rapidly compute atomic charges with accuracy comparable to quantum mechanical approaches. Due to its efficient implementation, ACC can handle any type of molecular system, regardless of size and chemical complexity, from drug-like molecules to biomacromolecular complexes with hundreds of thousands of atoms. ACC writes out atomic charges into common molecular structure files, and offers interactive facilities for statistical analysis and comparison of the results, in both tabular and graphical form. Due to high customizability and speed, easy streamlining and the unified platform for calculation and analysis, ACC caters to all fields of life sciences, from drug design to nanocarriers. ACC is freely available via the Internet at http://ncbr.muni.cz/ACC.

Driver's behavioral adaptation to adaptive cruise control (ACC): the case of speed and time headway.

PubMed

Bianchi Piccinini, Giulio Francesco; Rodrigues, Carlos Manuel; Leitão, Miguel; Simões, Anabela

2014-06-01

The Adaptive Cruise Control is an Advanced Driver Assistance System (ADAS) that allows maintaining given headway and speed, according to settings pre-defined by the users. Despite the potential benefits associated to the utilization of ACC, previous studies warned against negative behavioral adaptations that might occur while driving with the system activated. Unfortunately, up to now, there are no unanimous results about the effects induced by the usage of ACC on speed and time headway to the vehicle in front. Also, few studies were performed including actual users of ACC among the subjects. This research aimed to investigate the effect of the experience gained with ACC on speed and time headway for a group of users of the system. In addition, it explored the impact of ACC usage on speed and time headway for ACC users and regular drivers. A matched sample driving simulator study was planned as a two-way (2×2) repeated measures mixed design, with the experience with ACC as between-subjects factor and the driving condition (with ACC and manually) as within-subjects factor. The results show that the usage of ACC brought a small but not significant reduction of speed and, especially, the maintenance of safer time headways, being the latter result greater for ACC users, probably as a consequence of their experience in using the system. The usage of ACC did not cause any negative behavioral adaptations to the system regarding speed and time headway. Based on this research work, the Adaptive Cruise Control showed the potential to improve road safety for what concerns the speed and the time headway maintained by the drivers. The speed of the surrounding traffic and the minimum time headway settable through the ACC seem to have an important effect on the road safety improvement achievable with the system. Copyright © 2014 Elsevier Ltd. All rights reserved.

[The anaesthesia and critical care specialty and new hospital management in France: an inquiry in university and general hospitals].

PubMed

Fusciardi, J; Remérand, F; Landais, A; Brodeur, J; Journois, D; Laffon, M

2010-03-01

To know: (1) how French public services of anaesthesia and critical care (ACC) have applied the new principles of hospital management and (2) whether or not it has impacted the different components of ACC. National questionnaire at the end of 2008, i.e., after 2 years of new hospital management. Heads of ACC services in general (GH) and university hospitals (UH). Eighteen closed questions and open opinions analyzed. Comparisons of percentages (Chi(2) - Yates): linear correlation. Percentages of responses were 70% (n=51) for UH and 37% (n=146) for GH. The new management principles were mainly applied. The different clinical and academic components of the ACC specialty (ACC, emergency medicine, pain management) mainly remained associated in UH. In GH, the new management induced constant and various changes. They were mainly judged as defeating the object of the ACC speciality in GH, especially in those of lower and mild sizes. The general tendency is that the ACC specialty was able to maintain the family ties of its different components in the UH. However, this principle was not a cornerstone of the new management in the GH. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

24 CFR 982.355 - Portability: Administration by receiving PHA.

Code of Federal Regulations, 2011 CFR

2011-04-01

... by the receiving PHA. (1) If funding is available under the consolidated ACC for the receiving PHA... consolidated ACC for the receiving PHA tenant-based program. (2) HUD may require that the receiving PHA absorb... families to the receiving PHA from funds available under the initial PHA ACC. (2) HUD may provide...

24 CFR 982.355 - Portability: Administration by receiving PHA.

Code of Federal Regulations, 2010 CFR

2010-04-01

... by the receiving PHA. (1) If funding is available under the consolidated ACC for the receiving PHA... consolidated ACC for the receiving PHA tenant-based program. (2) HUD may require that the receiving PHA absorb... families to the receiving PHA from funds available under the initial PHA ACC. (2) HUD may provide...

Precipitation of ACC in liposomes-a model for biomineralization in confined volumes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tester, Chantel C; Wu, Ching-Hsuan; Weigand, Steven

2013-01-10

Biomineralizing organisms frequently precipitate minerals in small phospholipid bilayer-delineated compartments. We have established an in vitro model system to investigate the effect of confinement in attoliter to femtoliter volumes on the precipitation of calcium carbonate. In particular, we analyze the growth and stabilization of liposome-encapsulated amorphous calcium carbonate (ACC) nanoparticles using a combination of in situ techniques, cryo-transmission electron microscopy (Cryo-TEM), and small angle X-ray scattering (SAXS). Herein, we discuss ACC nanoparticle growth rate as a function of liposome size, carbon dioxide flux across the liposome membrane, pH, and osmotic pressure. Based on these experiments, we argue that the stabilizationmore » of ACC nanoparticles in liposomes is a consequence of a low nucleation rate (high activation barrier) of crystalline polymorphs of calcium carbonate.« less

Inactivation of 1-aminocyclopropane-1-carboxylate oxidase involves oxidative modifications.

PubMed

Barlow, J N; Zhang, Z; John, P; Baldwin, J E; Schofield, C J

1997-03-25

1-Aminocyclopropane-1-carboxylate (ACC) oxidase catalyzes the final step in the biosynthesis of the plant signaling molecule ethylene. It is a member of the ferrous iron dependent family of oxidases and dioxygenases and is unusual in that it displays a very short half-life under catalytic conditions, typically less than 20 min, and a requirement for CO2 as an activator. The rates of inactivation of purified, recombinant ACC oxidase from tomato under various combinations of substrates and cofactors were measured. Inactivation was relatively slow in the presence of buffer alone (t1/2 > 1 h), but fast in the presence of ferrous iron and ascorbate (t1/2 approximately 10 min). The rate of iron/ascorbate-mediated inactivation was increased by the addition of ACC, unaffected by the addition of CO2 at saturation (supplied as bicarbonate) but decreased by the addition of catalase or ACC + CO2 at saturation (supplied as bicarbonate). Iron/ascorbate-mediated inactivation was accompanied by partial proteolysis as observed by SDS-PAGE analysis. The fragmentation pattern was altered when ACC was also included, suggesting that ACC can bind to ACC oxidase in the absence of bicarbonate. N-terminal sequencing of fragments resulted in identification of an internal cleavage site which we propose is proximate to active-site bound iron. Thus, ACC oxidase inactivates via relatively slow partial unfolding of the catalytically active conformation, oxidative damage mediated via hydrogen peroxide which is catalase protectable and oxidative damage to the active site which results in partial proteolysis and is not catalase protectable.

Conflict effects without conflict in anterior cingulate cortex: multiple response effects and context specific representations

PubMed Central

Brown, Joshua W.

2009-01-01

The error likelihood computational model of anterior cingulate cortex (ACC) (Brown & Braver, 2005) has successfully predicted error likelihood effects, risk prediction effects, and how individual differences in conflict and error likelihood effects vary with trait differences in risk aversion. The same computational model now makes a further prediction that apparent conflict effects in ACC may result in part from an increasing number of simultaneously active responses, regardless of whether or not the cued responses are mutually incompatible. In Experiment 1, the model prediction was tested with a modification of the Eriksen flanker task, in which some task conditions require two otherwise mutually incompatible responses to be generated simultaneously. In that case, the two response processes are no longer in conflict with each other. The results showed small but significant medial PFC effects in the incongruent vs. congruent contrast, despite the absence of response conflict, consistent with model predictions. This is the multiple response effect. Nonetheless, actual response conflict led to greater ACC activation, suggesting that conflict effects are specific to particular task contexts. In Experiment 2, results from a change signal task suggested that the context dependence of conflict signals does not depend on error likelihood effects. Instead, inputs to ACC may reflect complex and task specific representations of motor acts, such as bimanual responses. Overall, the results suggest the existence of a richer set of motor signals monitored by medial PFC and are consistent with distinct effects of multiple responses, conflict, and error likelihood in medial PFC. PMID:19375509

24 CFR 884.122 - Separate project requirement.

Code of Federal Regulations, 2010 CFR

2010-04-01

... separate ACC List and ACC Part I and shall be assigned a separate project number. All new construction... construction projects where: (1) The units are placed under ACC on the same date; and (2) Such consolidation is...

24 CFR 884.122 - Separate project requirement.

Code of Federal Regulations, 2011 CFR

2011-04-01

... separate ACC List and ACC Part I and shall be assigned a separate project number. All new construction... construction projects where: (1) The units are placed under ACC on the same date; and (2) Such consolidation is...

Anterior cingulate cortex activity can be independent of response conflict in Stroop-like tasks.

PubMed

Roelofs, Ardi; van Turennout, Miranda; Coles, Michael G H

2006-09-12

Cognitive control includes the ability to formulate goals and plans of action and to follow these while facing distraction. Previous neuroimaging studies have shown that the presence of conflicting response alternatives in Stroop-like tasks increases activity in dorsal anterior cingulate cortex (ACC), suggesting that the ACC is involved in cognitive control. However, the exact nature of ACC function is still under debate. The prevailing conflict detection hypothesis maintains that the ACC is involved in performance monitoring. According to this view, ACC activity reflects the detection of response conflict and acts as a signal that engages regulative processes subserved by lateral prefrontal brain regions. Here, we provide evidence from functional MRI that challenges this view and favors an alternative view, according to which the ACC has a role in regulation itself. Using an arrow-word Stroop task, subjects responded to incongruent, congruent, and neutral stimuli. A critical prediction made by the conflict detection hypothesis is that ACC activity should be increased only when conflicting response alternatives are present. Our data show that ACC responses are larger for neutral than for congruent stimuli, in the absence of response conflict. This result demonstrates the engagement of the ACC in regulation itself. A computational model of Stroop-like performance instantiating a version of the regulative hypothesis is shown to account for our findings.

Phase transitions in biogenic amorphous calcium carbonate.

PubMed

Gong, Yutao U T; Killian, Christopher E; Olson, Ian C; Appathurai, Narayana P; Amasino, Audra L; Martin, Michael C; Holt, Liam J; Wilt, Fred H; Gilbert, P U P A

2012-04-17

Crystalline biominerals do not resemble faceted crystals. Current explanations for this property involve formation via amorphous phases. Using X-ray absorption near-edge structure (XANES) spectroscopy and photoelectron emission microscopy (PEEM), here we examine forming spicules in embryos of Strongylocentrotus purpuratus sea urchins, and observe a sequence of three mineral phases: hydrated amorphous calcium carbonate (ACC · H(2)O) → dehydrated amorphous calcium carbonate (ACC) → calcite. Unexpectedly, we find ACC · H(2)O-rich nanoparticles that persist after the surrounding mineral has dehydrated and crystallized. Protein matrix components occluded within the mineral must inhibit ACC · H(2)O dehydration. We devised an in vitro, also using XANES-PEEM, assay to identify spicule proteins that may play a role in stabilizing various mineral phases, and found that the most abundant occluded matrix protein in the sea urchin spicules, SM50, stabilizes ACC · H(2)O in vitro.

The political (and physiological) divide: Political orientation, performance monitoring, and the anterior cingulate response.

PubMed

Weissflog, Meghan; Choma, Becky L; Dywan, Jane; van Noordt, Stefon J R; Segalowitz, Sidney J

2013-01-01

Our goal was to test a model of sociopolitical attitudes that posits a relationship between individual differences in liberal versus conservative political orientation and differential levels of anterior cingulate cortex (ACC) responsivity. We recorded event-related potentials (ERPs) while participants who varied along a unidimensional liberal-conservative continuum engaged in a standard Go/NoGo task. We also measured component attitudes of political orientation in the form of traditionalism (degree of openness to social change) and egalitarianism (a preference for social equality). Generally, participants who reported a more liberal political orientation made fewer errors and produced larger ACC-generated ERPs (the error-related negativity, or ERN and the NoGo N2). This ACC activation, especially as indicated by a larger NoGo N2, was most strongly associated with greater preference for social equality. Performance accuracy, however, was most strongly associated with greater openness to social change. These data are consistent with a social neuroscience view that sociopolitical attitudes are related to aspects of neurophysiological responsivity. They also indicate that a bidimensional model of political orientation can enhance our interpretation of the nature of these associations.

Impact of the Agulhas Return Current on the glacial Subantarctic region in the South Indian Ocean

NASA Astrophysics Data System (ADS)

Ikehara, M.; Crosta, X.; Manoj, M. C.

2017-12-01

The Southern Ocean has played an important role in the evolution of the global climate system. The Southern Ocean circulation is dominated by the Antarctic Circumpolar Current (ACC), the world's longest and largest current system. Sea ice coverage on sea surface strongly affects the climate of the Southern Hemisphere through its impacts on the energy and gas budget, on the atmospheric circulation, on the hydrological cycle, and on the biological productivity. The Agulhas Return Current (ARC) originates from the Agulhas Current, the major western boundary current in the Indian Ocean, and transports heat from subtropical to subantarctic region. It's thought that the Agulhas leakage from the Indian Ocean to the Atlantic was reduced for the last glacial due to a northward shift of the westerlies and ACC, however, there are still unknown yet how the ARC was responded to the reduced Agulhas leakage. A piston core DCR-1PC was collected from the Del Caño Rise (46°S, 44°E, 2632m), Indian sector of the Southern Ocean. Core site located in the Subantarctic region between the Subtropical Front (STF) and Subantarctic Front (SAF). Age model of the core was established by radiocarbon dating of planktic foraminifer Globorotalia bulloides and oxygen isotope stratigraphy of benthic foraminifers Cibicidoides wuellerstorfi and Melonis bareelanus. Sediment of DCR-1PC show the cyclic changes of diatom/carbonate ooze sedimentation corresponding to Southern Ocean fronts' migrations on glacial-interglacial timescales. Records of ice-rafted debris (IRD) and oxygen isotope in planktic foraminfer G. bulloides suggest that the melting of sea ice was significantly increased during the last glacial maximum (LGM) in the Subantarctic surface water. Diatom assemblage based summer SST also shows the relative warmer condition in the Subantarctic during the LGM. These results might be explained by the strong influence of the Agulhas Return Current during the LGM in the Subantarctic. The reduced Agulhas leakage due to a northward shift of the westerlies and ACC impacted significantly on sea ice melting in the glacial Subantarctic region in the South Indian Ocean.

Environmental responses of the Northeast Antarctic Peninsula to the Holocene climate variability

NASA Astrophysics Data System (ADS)

Barbara, Loïc.; Crosta, Xavier; Leventer, Amy; Schmidt, Sabine; Etourneau, Johan; Domack, Eugene; Massé, Guillaume

2016-01-01

In this study, we present a unique high-resolution Holocene record of oceanographic and climatic change based on analyses of diatom assemblages combined with biomarker data from a sediment core collected from the Vega Drift, eastern Antarctic Peninsula (EAP). These data add to the climate framework already established by high-resolution marine sedimentary records from the Palmer Deep, western Antarctic Peninsula (WAP). Heavy sea ice conditions and reduced primary productivity were observed prior to 7.4 ka B.P. in relation with the proximity of the glacial ice melt and calving. Subsequent Holocene oceanographic conditions were controlled by the interactions between the Westerlies-Antarctic Circumpolar Current (ACC)-Weddell Gyre dynamics. A warm period characterized by short seasonal sea ice duration associated with a southern shift of both ACC and Westerlies field persisted until 5 ka B.P. This warm episode was then followed by climate deterioration during the middle-to-late Holocene (5 to 1.9 ka B.P.) with a gradual increase in annual sea ice duration triggered by the expansion of the Weddell Gyre and a strong oceanic connection from the EAP to the WAP. Increase of benthic diatom species during this period was indicative of more summer/autumn storms, which was consistent with changes in synoptic atmospheric circulation and the establishment of low- to high-latitude teleconnections. Finally, the multicentennial scale variability of the Weddell Gyre intensity and storm frequency during the late Holocene appeared to be associated with the increased El Niño-Southern Oscillation frequency.

Birth, life and death of an Anticyclonic eddy in the Southern Ocean

NASA Astrophysics Data System (ADS)

Torres, R.; Sallee, J. B.; Schwarz, J.; Hosegood, P. J.; Taylor, J. R.; Adams, K.; Bachman, S.; Stamper, M. A.

2016-02-01

The Antarctic Circumpolar Current (ACC) is a climatically relevant frontal structure of global importance, which regularly develops instabilities growing into meanders, and eventually evolving into long-lived anticyclonic eddies. These eddies exhibit sustained primary productivity that can last several months fuelled by local resupply of nutrients. During April-May 2015 we conducted an intensive field experiment in the Southern Ocean where we sampled and tracked an ACC meander as it developed into an eddy and later vanished some 90 days later. The physical characteristics of the meander and eddy were observed with a combination of high resolution hydrography, ADCP and turbulence observations, in addition to biogeochemical observations of nutrients and phytoplankton. The life and death of the eddy was subsequently tracked through Argo, BIO-Argo Lagrangian profilers and remote sensing. In this presentation we will use observations and ecosystem modelling to discuss the physical processes that sustain the observed high Chlorophyll levels in the eddy and explore how the eddy evolution impacts the rate of nutrient supply and how this translates into the observed changes in chlorophyll. We will discuss the relevance of eddy formation to Chlorophyll and productivity in the region.

Instability of cooperative adaptive cruise control traffic flow: A macroscopic approach

NASA Astrophysics Data System (ADS)

Ngoduy, D.

2013-10-01

This paper proposes a macroscopic model to describe the operations of cooperative adaptive cruise control (CACC) traffic flow, which is an extension of adaptive cruise control (ACC) traffic flow. In CACC traffic flow a vehicle can exchange information with many preceding vehicles through wireless communication. Due to such communication the CACC vehicle can follow its leader at a closer distance than the ACC vehicle. The stability diagrams are constructed from the developed model based on the linear and nonlinear stability method for a certain model parameter set. It is found analytically that CACC vehicles enhance the stabilization of traffic flow with respect to both small and large perturbations compared to ACC vehicles. Numerical simulation is carried out to support our analytical findings. Based on the nonlinear stability analysis, we will show analytically and numerically that the CACC system better improves the dynamic equilibrium capacity over the ACC system. We have argued that in parallel to microscopic models for CACC traffic flow, the newly developed macroscopic will provide a complete insight into the dynamics of intelligent traffic flow.

Premature Aging Phenotype in Mice Lacking High-Affinity Nicotinic Receptors: Region-Specific Changes in Layer V Pyramidal Cell Morphology.

PubMed

Konsolaki, Eleni; Skaliora, Irini

2015-08-01

The mechanisms by which aging leads to alterations in brain structure and cognitive deficits are unclear. Α deficient cholinergic system has been implicated as one of the main factors that could confer a heightened vulnerability to the aging process, and mice lacking high-affinity nicotinic receptors (β2(-/-)) have been proposed as an animal model of accelerated cognitive aging. To date, however, age-related changes in neuronal microanatomy have not been studied in these mice. In the present study, we examine the neuronal structure of yellow fluorescent protein (YFP(+)) layer V neurons in 2 cytoarchitectonically distinct cortical regions in wild-type (WT) and β2(-/-) animals. We find that (1) substantial morphological differences exist between YFP(+) cells of the anterior cingulate cortex (ACC) and primary visual cortex (V1), in both genotypes; (2) in WT animals, ACC cells are more susceptible to aging compared with cells in V1; and (3) β2 deletion is associated with a regionally and temporally specific increase in vulnerability to aging. ACC cells exhibit a prematurely aged phenotype already at 4-6 months, whereas V1 cells are spared in adulthood but strongly affected in old animals. Collectively, our data reveal region-specific synergistic effects of aging and genotype and suggest distinct vulnerabilities in V1 and ACC neurons. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Morphological heterogeneity of oral salivary gland carcinomas: A clinicopathologic study of 41 cases with long term follow-up emphasizing the overlapping spectrum of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma

PubMed Central

Schwarz, Stephan; Müller, Maximilian; Ettl, Tobias; Stockmann, Philipp; Zenk, Johannes; Agaimy, Abbas

2011-01-01

We analyzed 41 oral salivary gland carcinomas from consecutive 290 salivary gland carcinoma database (14%) with emphasis on the histological spectrum and clinical outcome of adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA). The cohort included 14 ACCs, 14 mucoepidermoid carcinomas (MECs), 8 PLGAs, 3 adenocarcinomas, not otherwise specified and 2 acinic cell carcinomas. Mean age was 48, 58 and 61 yrs for ACC, MEC and PLGA, respectively. Eight patients (19.5%) died of tumor at a mean interval of 66.5 months. ACC and PLGA showed similar mean age, gender distribution, predominant palatal localization, nodal metastasis, perineural invasion and MIB-1 index. However, ACC tended to show higher tumor stage and residual tumor (R1/R2) more frequently than PLGA, but this was statistically not significant. ACC and PLGA showed overlapping architectural patterns. However, ACCs displayed well organized basal-luminal differentiation, highlighted by CK5/CK7 immunostaining. In contrast, PLGA showed a disorganized histological and immunohistological pattern. C-Kit expression (CD117) was common in ACC, generally mirroring that of CK7 and virtually lacking in PLGA. Kaplan-Meier analysis demonstrated a similar clinical course for ACC and PLGA with 5 years survivals of 87% and 80%, respectively. Fluorescence in situ hybridization (FISH) performed on all 290 salivary carcinomas confirmed the specificity of the translocation t (11; 19) for MEC and its absence in all other carcinomas including ACC and PLGA. Our results emphasize the diversity of oral salivary gland carcinomas and the overlapping clinicopathological features of ACC and PLGA. PMID:21577319

The Repeat Sequences and Elevated Substitution Rates of the Chloroplast accD Gene in Cupressophytes

PubMed Central

Li, Jia; Su, Yingjuan; Wang, Ting

2018-01-01

The plastid accD gene encodes a subunit of the acetyl-CoA carboxylase (ACCase) enzyme. The length of accD gene has been supposed to expand in Cryptomeria japonica, Taiwania cryptomerioides, Cephalotaxus, Taxus chinensis, and Podocarpus lambertii, and the main reason for this phenomenon was the existence of tandemly repeated sequences. However, it is still unknown whether the accD gene length in other cupressophytes has expanded. Here, in order to investigate how widespread this phenomenon was, 18 accD sequences and its surrounding regions of cupressophyte were sequenced and analyzed. Together with 39 GenBank sequence data, our taxon sampling covered all the extant gymnosperm orders. The repetitive elements and substitution rates of accD among 57 gymnosperm species were analyzed, the results show: (1) Reading frame length of accD gene in 18 cupressophytes species has also expanded. (2) Many repetitive elements were identified in accD gene of cupressophyte lineages. (3) The synonymous and non-synonymous substitution rates of accD were accelerated in cupressophytes. (4) accD was located in rearrangement endpoints. These results suggested that repetitive elements may mediate the chloroplast genome rearrangement and accelerated the substitution rates. PMID:29731764

Efficient Plastid Transformation in Arabidopsis.

PubMed

Yu, Qiguo; Lutz, Kerry Ann; Maliga, Pal

2017-09-01

Plastid transformation is routine in tobacco ( Nicotiana tabacum ) but 100-fold less frequent in Arabidopsis ( Arabidopsis thaliana ), preventing its use in plastid biology. A recent study revealed that null mutations in ACC2 , encoding a plastid-targeted acetyl-coenzyme A carboxylase, cause hypersensitivity to spectinomycin. We hypothesized that plastid transformation efficiency should increase in the acc2 background, because when ACC2 is absent, fatty acid biosynthesis becomes dependent on translation of the plastid-encoded ACC β-carboxylase subunit. We bombarded ACC2 -defective Arabidopsis leaves with a vector carrying a selectable spectinomycin resistance ( aadA ) gene and gfp , encoding the green fluorescence protein GFP. Spectinomycin-resistant clones were identified as green cell clusters on a spectinomycin medium. Plastid transformation was confirmed by GFP accumulation from the second open reading frame of a polycistronic messenger RNA, which would not be translated in the cytoplasm. We obtained one to two plastid transformation events per bombarded sample in spectinomycin-hypersensitive Slavice and Columbia acc2 knockout backgrounds, an approximately 100-fold enhanced plastid transformation frequency. Slavice and Columbia are accessions in which plant regeneration is uncharacterized or difficult to obtain. A practical system for Arabidopsis plastid transformation will be obtained by creating an ACC2 null background in a regenerable Arabidopsis accession. The recognition that the duplicated ACCase in Arabidopsis is an impediment to plastid transformation provides a rational template to implement plastid transformation in related recalcitrant crops. © 2017 American Society of Plant Biologists. All Rights Reserved.

Soraphen A, an inhibitor of acetyl CoA carboxylase activity, interferes with fatty acid elongation

PubMed Central

Jump, Donald B.; Torres-Gonzalez, Moises; Olson, L. Karl

2010-01-01

Acetyl CoA carboxylase (ACC1 & ACC2) generates malonyl CoA, a substrate for de novo lipogenesis (DNL) and an inhibitor of mitochondrial fatty acid β-oxidation (FAO). Malonyl CoA is also a substrate for microsomal fatty acid elongation, an important pathway for saturated (SFA), mono- (MUFA) and polyunsaturated fatty acid (PUFA) synthesis. Despite the interest in ACC as a target for obesity and cancer therapy, little attention has been given to the role ACC plays in long chain fatty acid synthesis. This report examines the effect of pharmacological inhibition of ACC on DNL & palmitate (16:0) and linoleate (18:2,n-6) metabolism in HepG2 and LnCap cells. The ACC inhibitor, soraphen A, lowers cellular malonyl CoA, attenuates DNL and the formation of fatty acid elongation products derived from exogenous fatty acids, i.e., 16:0 & 18:2,n-6; IC50 ~ 5 nM. Elevated expression of fatty acid elongases (Elovl5, Elovl6) or desaturases (FADS1, FADS2) failed to override the soraphen A effect on SFA, MUFA or PUFA synthesis. Inhibition of fatty acid elongation leads to the accumulation of 16- and 18-carbon unsaturated fatty acids derived from 16:0 and 18:2,n-6, respectively. Pharmacological inhibition of ACC activity will not only attenuate DNL and induce FAO, but will also attenuate the synthesis of very long chain saturated, mono- and polyunsaturated fatty acids. PMID:21184748

Driver behaviour with adaptive cruise control.

PubMed

Stanton, Neville A; Young, Mark S

2005-08-15

This paper reports on the evaluation of adaptive cruise control (ACC) from a psychological perspective. It was anticipated that ACC would have an effect upon the psychology of driving, i.e. make the driver feel like they have less control, reduce the level of trust in the vehicle, make drivers less situationally aware, but workload might be reduced and driving might be less stressful. Drivers were asked to drive in a driving simulator under manual and ACC conditions. Analysis of variance techniques were used to determine the effects of workload (i.e. amount of traffic) and feedback (i.e. degree of information from the ACC system) on the psychological variables measured (i.e. locus of control, trust, workload, stress, mental models and situation awareness). The results showed that: locus of control and trust were unaffected by ACC, whereas situation awareness, workload and stress were reduced by ACC. Ways of improving situation awareness could include cues to help the driver predict vehicle trajectory and identify conflicts.

Reliability and Validity of 2 Self-Report Measures to Assess Sedentary Behavior in Older Adults.

PubMed

Gennuso, Keith P; Matthews, Charles E; Colbert, Lisa H

2015-05-01

The purpose of this study was to examine the reliability and validity of 2 currently available physical activity surveys for assessing time spent in sedentary behavior (SB) in older adults. Fifty-eight adults (≥65 years) completed the Yale Physical Activity Survey for Older Adults (YPAS) and Community Health Activities Model Program for Seniors (CHAMPS) before and after a 10-day period during which they wore an ActiGraph accelerometer (ACC). Intraclass correlation coefficients (ICC) examined test-retest reliability. Overall percent agreement and a kappa statistic examined YPAS validity. Lin's concordance correlation, Pearson correlation, and Bland-Altman analysis examined CHAMPS validity. Both surveys had moderate test-retest reliability (ICC: YPAS = 0.59 (P < .001), CHAMPS = 0.64 (P < .001)) and significantly underestimated SB time. Agreement between YPAS and ACC was low (κ = -0.0003); however, there was a linear increase (P < .01) in ACC-derived SB time across YPAS response categories. There was poor agreement between ACC-derived SB and CHAMPS (Lin's r = .005; 95% CI, -0.010 to 0.020), and no linear trend across CHAMPS quartiles (P = .53). Neither of the surveys should be used as the sole measure of SB in a study; though the YPAS has the ability to rank individuals, providing it with some merit for use in correlational SB research.

Inventory of File sref_em.t03z.pgrb212.p1.f06.grib2

Science.gov Websites

surface WEASD 6 hour fcst Water Equivalent of Accumulated Snow Depth [kg/m^2] 016 surface APCP 0-6 hour surface WEASD 0-6 hour acc Water Equivalent of Accumulated Snow Depth [kg/m^2] 019 surface CSNOW 6 hour -6 hour acc Large-Scale Precipitation (non-convective) [kg/m^2] 415 surface SNOM 0-6 hour acc Snow

ACC Effectiveness Review, 1999-2002.

ERIC Educational Resources Information Center

Wallace, Roslyn, Ed.

2002-01-01

These newsletters on Institutional Effectiveness (IE) at Austin Community College (ACC) in Texas include the following articles: (1) "The 'Fast Track'...Students Say It Works!" (2) "Are Students Successfully Completing Distance Learning Courses at ACC?" (3) "Tracking Transfers"; (4) "Math Pilot: Study Skills…

Inventory of File sref_nmm.t03z.pgrb221.p1.f00.grib2

Science.gov Websites

ground VGRD analysis V-Component of Wind [m/s] 015 surface WEASD analysis Water Equivalent of Accumulated day acc f Convective Precipitation [kg/m^2] 018 surface WEASD 0-0 day acc f Water Equivalent of Potential Temperature [K] 403 surface NCPCP 0-0 day acc f Large-Scale Precipitation (non-convective) [kg/m^2

Inventory of File sref_nmb.t03z.pgrb221.p1.f00.grib2

Science.gov Websites

ground VGRD analysis V-Component of Wind [m/s] 015 surface WEASD analysis Water Equivalent of Accumulated day acc f Convective Precipitation [kg/m^2] 018 surface WEASD 0-0 day acc f Water Equivalent of Potential Temperature [K] 403 surface NCPCP 0-0 day acc f Large-Scale Precipitation (non-convective) [kg/m^2

Neural correlates of appetitive extinction in humans.

PubMed

Kruse, Onno; Tapia León, Isabell; Stark, Rudolf; Klucken, Tim

2017-01-01

Appetitive extinction receives attention as an important model for the treatment of psychiatric disorders. However, in humans, its underlying neural correlates remain unknown. To close this gap, we investigated appetitive acquisition and extinction with fMRI in a 2-day monetary incentive delay paradigm. During appetitive conditioning, one stimulus (CS+) was paired with monetary reward, while another stimulus (CS-) was never rewarded. Twenty-four hours later, subjects underwent extinction, in which neither CS was reinforced. Appetitive conditioning elicited stronger skin conductance responses to the CS+ as compared with the CS-. Regarding subjective ratings, the CS+ was rated more pleasant and arousing than the CS- after conditioning. Furthermore, fMRI-results (CS+ - CS-) showed activation of the reward circuitry including amygdala, midbrain and striatal areas. During extinction, conditioned responses were successfully extinguished. In the early phase of extinction, we found a significant activation of the caudate, the hippocampus, the dorsal and ventral anterior cingulate cortex (dACC and vACC). In the late phase, we found significant activation of the nucleus accumbens (NAcc) and the amygdala. Correlational analyses with subjective ratings linked extinction success to the vACC and the NAcc, while associating the dACC with reduced extinction. The results reveal neural correlates of appetitive extinction in humans and extend assumptions from models for human extinction learning. © The Author (2016). Published by Oxford University Press.

Effect of thiosulfate on rapid start-up of sulfur-based reduction of high concentrated perchlorate: A study of kinetics, extracellular polymeric substances (EPS) and bacterial community structure.

PubMed

Guo, Jianbo; Zhang, Chao; Lian, Jing; Lu, Caicai; Chen, Zhi; Song, Yuanyuan; Guo, Yankai; Xing, Yajuan

2017-11-01

Perchlorate (ClO 4 - ) contamination is more and more concerned due to the hazards to humans. Based on the common primary bacterium (Helicobacteraceae) of both thiosulfate-acclimated sludge (T-Acc) and sulfur-acclimated sludge (S-Acc) for perchlorate reduction, the rapid start-up of sulfur-based perchlorate reduction reactor (SBPRR) was hypothesized by inoculating T-Acc. Furthermore, the performance of SBPRR, the SO 4 2- yield, kinetics of ClO 4 - reduction and the extracellular polymeric substances (EPS) of biofilm confirmed the hypothesis. The start-up time of R3 (reactor inoculating T-Acc) was 0.18 and 0.21 times that of R1 (control) and R2 (reactor with the influent containing thiosulfate), respectively. The SO 4 2- yield of R3 was lower than that of R2 and R1 with perchlorate removal rate 166.7mg/(Lh). The kinetic study and EPS demonstrated that inoculating T-Acc was beneficial for the development of biofilm. Consequently, the present study indicated that SBPRR can be rapidly and successfully started-up via inoculation of T-Acc. Copyright © 2017 Elsevier Ltd. All rights reserved.

OpenACC performance for simulating 2D radial dambreak using FVM HLLE flux

NASA Astrophysics Data System (ADS)

Gunawan, P. H.; Pahlevi, M. R.

2018-03-01

The aim of this paper is to investigate the performances of openACC platform for computing 2D radial dambreak. Here, the shallow water equation will be used to describe and simulate 2D radial dambreak with finite volume method (FVM) using HLLE flux. OpenACC is a parallel computing platform based on GPU cores. Indeed, from this research this platform is used to minimize computational time on the numerical scheme performance. The results show the using OpenACC, the computational time is reduced. For the dry and wet radial dambreak simulations using 2048 grids, the computational time of parallel is obtained 575.984 s and 584.830 s respectively for both simulations. These results show the successful of OpenACC when they are compared with the serial time of dry and wet radial dambreak simulations which are collected 28047.500 s and 29269.40 s respectively.

Impaired Voluntary Control in PTSD: Probing Self-Regulation of the ACC With Real-Time fMRI

PubMed Central

Zweerings, Jana; Pflieger, Eliza M.; Mathiak, Krystyna A.; Zvyagintsev, Mikhail; Kacela, Anastasia; Flatten, Guido; Mathiak, Klaus

2018-01-01

Background: Post-traumatic stress disorder (PTSD) is characterized by deficits in the self-regulation of cognitions and emotions. Neural networks of emotion regulation may exhibit reduced control mediated by the anterior cingulate cortex (ACC), contributing to aberrant limbic responses in PTSD. Methods: Real-time fMRI neurofeedback (rt-fMRI NF) assessed self-regulation of the ACC in nine patients with PTSD after single trauma exposure and nine matched healthy controls. All participants were instructed to train ACC upregulation on three training days. Results: Both groups achieved regulation, which was associated with wide-spread brain activation encompassing the ACC. Compared to the controls, regulation amplitude and learning rate was lower in patients, correlating with symptom severity. In addition, a frontopolar activation cluster was associated with self-regulation efforts in patients. Conclusions: For the first time, we tested self-regulation of the ACC in patients with PTSD. The observed impairment supports models of ACC-mediated regulation deficits that may contribute to the psychopathology of PTSD. Controlled trials in a larger sample are needed to confirm our findings and to directly investigate whether training of central regulation mechanisms improves emotion regulation in PTSD. PMID:29899712

Impaired Voluntary Control in PTSD: Probing Self-Regulation of the ACC With Real-Time fMRI.

PubMed

Zweerings, Jana; Pflieger, Eliza M; Mathiak, Krystyna A; Zvyagintsev, Mikhail; Kacela, Anastasia; Flatten, Guido; Mathiak, Klaus

2018-01-01

Background: Post-traumatic stress disorder (PTSD) is characterized by deficits in the self-regulation of cognitions and emotions. Neural networks of emotion regulation may exhibit reduced control mediated by the anterior cingulate cortex (ACC), contributing to aberrant limbic responses in PTSD. Methods: Real-time fMRI neurofeedback (rt-fMRI NF) assessed self-regulation of the ACC in nine patients with PTSD after single trauma exposure and nine matched healthy controls. All participants were instructed to train ACC upregulation on three training days. Results: Both groups achieved regulation, which was associated with wide-spread brain activation encompassing the ACC. Compared to the controls, regulation amplitude and learning rate was lower in patients, correlating with symptom severity. In addition, a frontopolar activation cluster was associated with self-regulation efforts in patients. Conclusions: For the first time, we tested self-regulation of the ACC in patients with PTSD. The observed impairment supports models of ACC-mediated regulation deficits that may contribute to the psychopathology of PTSD. Controlled trials in a larger sample are needed to confirm our findings and to directly investigate whether training of central regulation mechanisms improves emotion regulation in PTSD.

Right Anterior Cingulate Cortical Thickness and Bilateral Striatal Volume Correlate with CBCL Aggressive Behavior Scores in Healthy Children

PubMed Central

Ducharme, Simon; Hudziak, James J; Botteron, Kelly N; Ganjavi, Hooman; Lepage, Claude; Collins, D Louis; Albaugh, Matthew D.; Evans, Alan C; Karama, Sherif

2011-01-01

Background The anterior cingulate cortex (ACC), orbito-frontal cortex (OFC) and basal ganglia have been implicated in pathological aggression. This study aimed at identifying neuroanatomical correlates of impulsive aggression in healthy children. Methods Data from 193 representative 6–18 year-old healthy children were obtained from the NIH MRI Study of Normal Brain Development after a blinded quality control (1). Cortical thickness and subcortical volumes were obtained with automated software. Aggression levels were measured with the Aggressive Behavior scale (AGG) of the Child Behavior Checklist (CBCL). AGG scores were regressed against cortical thickness and basal ganglia volumes using first and second-order linear models while controlling for age, gender, scanner site and total brain volume. ‘Gender by AGG’ interactions were analyzed. Results There were positive associations between bilateral striatal volumes and AGG scores (right: r=0.238, p=0.001; left: r=0.188, p=0.01). A significant association was found with right ACC and subgenual ACC cortical thickness in a second-order linear model (p<0.05, corrected). High AGG scores were associated with a relatively thin right ACC cortex. An ‘AGG by gender’ interaction trend was found in bilateral OFC and ACC associations with AGG scores. Conclusion This study shows the existence of relationships between impulsive aggression in healthy children and the structure of the striatum and right ACC. It also suggests the existence of gender specific patterns of association in OFC/ACC grey matter. These results may guide research on oppositional-defiant and conduct disorders. PMID:21531391

Right anterior cingulate cortical thickness and bilateral striatal volume correlate with child behavior checklist aggressive behavior scores in healthy children.

PubMed

Ducharme, Simon; Hudziak, James J; Botteron, Kelly N; Ganjavi, Hooman; Lepage, Claude; Collins, D Louis; Albaugh, Matthew D; Evans, Alan C; Karama, Sherif

2011-08-01

The anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and basal ganglia have been implicated in pathological aggression. This study aimed at identifying neuroanatomical correlates of impulsive aggression in healthy children. Data from 193 representative 6- to 18-year-old healthy children were obtained from the National Institutes of Health Magnetic Resonance Imaging Study of Normal Brain Development after a blinded quality control. Cortical thickness and subcortical volumes were obtained with automated software. Aggression levels were measured with the Aggressive Behavior scale (AGG) of the Child Behavior Checklist. AGG scores were regressed against cortical thickness and basal ganglia volumes using first- and second-order linear models while controlling for age, gender, scanner site, and total brain volume. Gender by AGG interactions were analyzed. There were positive associations between bilateral striatal volumes and AGG scores (right: r = .238, p = .001; left: r = .188, p = .01). A significant association was found with right ACC and subgenual ACC cortical thickness in a second-order linear model (p < .05, corrected). High AGG scores were associated with a relatively thin right ACC cortex. An AGG by gender interaction trend was found in bilateral OFC and ACC associations with AGG scores. This study shows the existence of relationships between impulsive aggression in healthy children and the structure of the striatum and right ACC. It also suggests the existence of gender-specific patterns of association in OFC/ACC gray matter. These results may guide research on oppositional-defiant and conduct disorders. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

ITSG-Grace2016 data preprocessing methodologies revisited: impact of using Level-1A data products

NASA Astrophysics Data System (ADS)

Klinger, Beate; Mayer-Gürr, Torsten

2017-04-01

For the ITSG-Grace2016 release, the gravity field recovery is based on the use of official GRACE (Gravity Recovery and Climate Experiment) Level-1B data products, generated by the Jet Propulsion Laboratory (JPL). Before gravity field recovery, the Level-1B instrument data are preprocessed. This data preprocessing step includes the combination of Level-1B star camera (SCA1B) and angular acceleration (ACC1B) data for an improved attitude determination (sensor fusion), instrument data screening and ACC1B data calibration. Based on a Level-1A test dataset, provided for individual month throughout the GRACE period by the Center of Space Research at the University of Texas at Austin (UTCSR), the impact of using Level-1A instead of Level-1B data products within the ITSG-Grace2016 processing chain is analyzed. We discuss (1) the attitude determination through an optimal combination of SCA1A and ACC1A data using our sensor fusion approach, (2) the impact of the new attitude product on temporal gravity field solutions, and (3) possible benefits of using Level-1A data for instrument data screening and calibration. As the GRACE mission is currently reaching its end-of-life, the presented work aims not only at a better understanding of GRACE science data to reduce the impact of possible error sources on the gravity field recovery, but it also aims at preparing Level-1A data handling capabilities for the GRACE Follow-On mission.

Dynamics of the Antarctic Circumpolar Current. Evidence for Topographic Effects from Altimeter Data and Numerical Model Output

NASA Technical Reports Server (NTRS)

Gille, Sarah T.

1995-01-01

Geosat altimeter data and numerical model output are used to examine the circulation and dynamics of the Antarctic Circumpolar Current (ACC). The mean sea surface height across the ACC has been reconstructed from height variability measured by the altimeter, without assuming prior knowledge of the geoid. The results indicate locations for the Subantarctic and Polar Fronts which are consistent with in situ observations and indicate that the fronts are substantially steered by bathymetry. Detailed examination of spatial and temporal variability indicates a spatial decorrelation scale of 85 km and a temporal e-folding scale of 34 days. Empirical Orthogonal Function analysis suggests that the scales of motion are relatively short, occuring on 1000 km length-scales rather than basin or global scales. The momentum balance of the ACC has been investigated using output from the high resolution primitive equation model in combination with altimeter data. In the Semtner-Chervin quarter-degree general circulation model topographic form stress is the dominant process balancing the surface wind forcing. In stream coordinates, the dominant effect transporting momentum across the ACC is bibarmonic friction. Potential vorticity is considered on Montgomery streamlines in the model output and along surface streamlines in model and altimeter data. (AN)

Molecular dynamic simulations and structure-based pharmacophore development for farnesyltransferase inhibitors discovery.

PubMed

Moorthy, N S Hari Narayana; Sousa, Sergio F; Ramos, Maria J; Fernandes, Pedro A

2016-12-01

Farnesyltransferase is one of the enzyme targets for the development of drugs for diseases, including cancer, malaria, progeria, etc. In the present study, the structure-based pharmacophore models have been developed from five complex structures (1LD7, 1NI1, 2IEJ, 2ZIR and 2ZIS) obtained from the protein data bank. Initially, molecular dynamic (MD) simulations were performed for the complexes for 10 ns using AMBER 12 software. The conformers of the complexes (75) generated from the equilibrated protein were undergone protein-ligand interaction fingerprint (PLIF) analysis. The results showed that some important residues, such as LeuB96, TrpB102, TrpB106, ArgB202, TyrB300, AspB359 and TyrB361, are predominantly present in most of the complexes for interactions. These residues form side chain acceptor and surface (hydrophobic or π-π) kind of interactions with the ligands present in the complexes. The structure-based pharmacophore models were generated from the fingerprint bits obtained from PLIF analysis. The pharmacophore models have 3-4 pharmacophore contours consist of acceptor and metal ligation (Acc & ML), hydrophobic (HydA) and extended acceptor (Acc2) features with the radius ranging between 1-3 Å for Acc & ML and 1-2 Å for HydA. The excluded volumes of the pharmacophore contours radius are between 1-2 Å. Further, the distance between the interacting groups, root mean square deviation (RMSD), root mean square fluctuation (RMSF) and radial distribution function (RDF) analysis were performed for the MD-simulated proteins using PTRAJ module. The generated pharmacophore models were used to screen a set of natural compounds and database compounds to select significant HITs. We conclude that the developed pharmacophore model can be a significant model for the identification of HITs as FTase inhibitors.

Acetyl CoA Carboxylase Inhibition Reduces Hepatic Steatosis but Elevates Plasma Triglycerides in Mice and Humans: A Bedside to Bench Investigation.

PubMed

Kim, Chai-Wan; Addy, Carol; Kusunoki, Jun; Anderson, Norma N; Deja, Stanislaw; Fu, Xiaorong; Burgess, Shawn C; Li, Cai; Ruddy, Marcie; Chakravarthy, Manu; Previs, Steve; Milstein, Stuart; Fitzgerald, Kevin; Kelley, David E; Horton, Jay D

2017-08-01

Inhibiting lipogenesis prevents hepatic steatosis in rodents with insulin resistance. To determine if reducing lipogenesis functions similarly in humans, we developed MK-4074, a liver-specific inhibitor of acetyl-CoA carboxylase (ACC1) and (ACC2), enzymes that produce malonyl-CoA for fatty acid synthesis. MK-4074 administered to subjects with hepatic steatosis for 1 month lowered lipogenesis, increased ketones, and reduced liver triglycerides by 36%. Unexpectedly, MK-4074 increased plasma triglycerides by 200%. To further investigate, mice that lack ACC1 and ACC2 in hepatocytes (ACC dLKO) were generated. Deletion of ACCs decreased polyunsaturated fatty acid (PUFA) concentrations in liver due to reduced malonyl-CoA, which is required for elongation of essential fatty acids. PUFA deficiency induced SREBP-1c, which increased GPAT1 expression and VLDL secretion. PUFA supplementation or siRNA-mediated knockdown of GPAT1 normalized plasma triglycerides. Thus, inhibiting lipogenesis in humans reduced hepatic steatosis, but inhibiting ACC resulted in hypertriglyceridemia due to activation of SREBP-1c and increased VLDL secretion. Copyright © 2017 Elsevier Inc. All rights reserved.

Absence of cytotoxic antibody to human immunodeficiency virus-infected cells in humans and its induction in animals after infection or immunization with purified envelope glycoprotein gp120

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nara, P.L.; Robey, W.G.; Gonda, M.A.

1987-06-01

The presence of antibody-dependent complement-mediated cytotoxicity (ACC) was assessed in humans and chimpanzees, which are capable of infection with human immunodeficiency virus isolate HTLV-IIIb, and examined in the goat after immunization with the major viral glycoprotein (gp120) of HTLV-IIIb. In infected humans no antibody mediating ACC was observed regardless of the status of disease. Even healthy individuals with high-titer, broadly reactive, neutralizing antibodies has no ACC. In contrast, chimpanzees infected with HTLV-IIIb, from whom virus could be isolated, not only had neutralizing antibody but also antibodies broadly reactive in ACC, even against distantly related human immunodeficiency virus isolates, as wellmore » as against their own reisolated virus. In the goat, the gp120 of HTLV-IIIb induced a highly type-specific response as measured by both ACC and flow cytofluorometry of live infected H9 cells. Normal human cells were not subject to ACC by animal anti-HTLV-III gp120-specific sera. Induction of ACC and neutralizing antibody were closely correlated in the animal experimental models but not in humans. The presence of ACC in gp120-inoculated goats and HTLV-III-infected chimpanzees represent a qualitative difference that may be important in the quest for the elicitation of a protective immunity in humans.« less

Identification of vascular patients at very high risk for recurrent cardiovascular events: validation of the current ACC/AHA very high risk criteria.

PubMed

van den Berg, M Johanneke; Bhatt, Deepak L; Kappelle, L Jaap; de Borst, Gert J; Cramer, Maarten J; van der Graaf, Yolanda; Steg, Ph Gabriel; Visseren, Frank L J

2017-11-14

To validate and assess performance of the current ACC/AHA very high risk criteria in patients with clinically manifest arterial disease. Data were used from the SMART study (n = 7216) and REACH Registry (n = 48 322), two prospective cohorts of patients with manifest atherosclerotic arterial disease. Prevalence and incidence rates of recurrent major adverse cardiovascular events (MACE) were calculated, according to the ACC/AHA VHR criteria (cardiovascular disease combined with diabetes, smoking, dyslipidaemia, and/or recent recurrent coronary events). Performance of the ACC/AHA criteria was compared with single very high risk factors in terms of C-statistics and Net Reclassification Index. All patients were at VHR according to the ESC guidelines (incidence of recurrent MACE in SMART was 2.4/100PY, with 95% CI 2.3-2.5/100PY and in REACH 5.1/100PY with 95% CI 5.0-5.3/100PY). In SMART 57% of the patients were at VHR according to the ACC/AHA criteria (incidence of recurrent MACE 2.7/100PY, 95% CI 2.5-2.9/100PY) and in REACH this was 64% (5.9/100PY, 95% CI 5.7-6.1/100PY). The C-statistic for the ACC/AHA VHR criteria was 0.53 in REACH and 0.54 in SMART. Very high risk factors with comparable or slightly better performance were eGFR < 45, polyvascular disease and age >70 years. Around two third of the patients meeting the ACC/AHA VHR criteria had a predicted 10-year risk of recurrent MACE <30%. The ACC/AHA VHR criteria have limited discriminative power. Identifying patients with clinically manifest arterial disease at VHR for recurrent vascular events using eGFR <45, polyvascular disease, or age >70 years performs as well as the ACC/AHA VHR criteria. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Physiological responses of horses to a treadmill simulated speed and endurance test in high heat and humidity before and after humid heat acclimation.

PubMed

Marlin, D J; Scott, C M; Schroter, R C; Harris, R C; Harris, P A; Roberts, C A; Mills, P C

1999-01-01

To investigate whether horses were able to acclimate to conditions of high temperature and humidity, 5 horses of different breeds were trained for 80 min on 15 consecutive days on a treadmill at 30 degrees C and 80%RH. Training consisted of a combination of long duration low-intensity exercise, medium duration medium intensity exercise and short duration high intensity exercise. Between training sessions the horses were maintained at 11+/-3 degrees C and 74+/-2%RH. Before (PRE-ACC) and after acclimation (POST-ACC) the horses undertook a simulated Competition Exercise Test (CET), designed to represent the Speed and Endurance Test of a 3-day event, at 30 degrees C/80%RH. Maximal oxygen uptake (VO2PEAK) was not changed following acclimation (PRE-ACC 141+/-8 ml/min/kg bwt vs. POST-ACC 145+/-9 ml/min/kg bwt [STPD], P>0.05). Following acclimation, 4 of the 5 horses were able to complete a significantly greater amount of Phase D in the CET (PRE-ACC 6.3+/-0.3 min vs. POST-ACC 7.3+/-0.3 min, P<0.05; target time = 8 min). Resting body temperatures (pulmonary artery [TPA], rectal [TREC] and tail-skin [TTSK] temperatures) were all significantly lower following acclimation. During exercise, metabolic heat production (M) and heat dissipation (HD), for the same exercise duration, were both significantly lower following acclimation (P<0.05), although heat storage (HS) was significantly higher (P<0.05). The higher heat storage following acclimation was associated with a lower TTSK for a given TPA and a decreased total fluid loss (% bodyweight, P<0.05). Plasma volume was not changed following acclimation. The relationship of sweating rate (SR) to TPA or TTSK on either the neck or the gluteal region was not significantly altered by acclimation, although the onset of sweating occurred at a lower TPA or TTSK following acclimation (P<0.05). The horses in the present study showed a number of physiological adaptations to a period of 15 days of exposure to high heat and humidity consistent with a humid heat acclimation response. These changes were mostly similar to those reported to occur in man and other species and were consistent with thermal acclimation and an increased thermotolerance, leading to an improved exercise tolerance. It is concluded that a 15 day period of acclimation is beneficial for horses from cooler and or drier climates, that have to compete in hot humid conditions and that this may redress, to some extent, the decrement in exercise tolerance seen in nonacclimated horses and reduce the risk of heat related disorders, such as heat exhaustion.

Stevioside improves pancreatic beta-cell function during glucotoxicity via regulation of acetyl-CoA carboxylase.

PubMed

Chen, Jianguo; Jeppesen, Per Bendix; Nordentoft, Iver; Hermansen, Kjeld

2007-06-01

Chronic hyperglycemia is detrimental to pancreatic beta-cells, causing impaired insulin secretion and beta-cell turnover. The characteristic secretory defects are increased basal insulin secretion (BIS) and a selective loss of glucose-stimulated insulin secretion (GSIS). Several recent studies support the view that the acetyl-CoA carboxylase (ACC) plays a pivotal role for GSIS. We have shown that stevioside (SVS) enhances insulin secretion and ACC gene expression. Whether glucotoxicity influences ACC and whether this action can be counteracted by SVS are not known. To investigate this, we exposed isolated mouse islets as well as clonal INS-1E beta-cells for 48 h to 27 or 16.7 mM glucose, respectively. We found that 48-h exposure to high glucose impairs GSIS from mouse islets and INS-1E cells, an effect that is partly counteracted by SVS. The ACC dephosphorylation inhibitor okadaic acid (OKA, 10(-8) M), and 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR, 10(-4) M), an activator of 5'-AMP protein kinase that phosphorylates ACC, eliminated the beneficial effect of SVS. 5-Tetrade-cyloxy-2-furancarboxylic acid (TOFA), the specific ACC inhibitor, blocked the effect of SVS as well. During glucotoxity, ACC gene expression, ACC protein, and phosphorylated ACC protein were increased in INS-1E beta-cells. SVS pretreatment further increased ACC gene expression with strikingly elevated ACC activity and increased glucose uptake accompanied by enhanced GSIS. Our studies show that glucose is a potent stimulator of ACC and that SVS to some extent counteracts glucotoxicity via increased ACC activity. SVS possesses the potential to alleviate negative effects of glucotoxicity in beta-cells via a unique mechanism of action.

ACC/AHA guidelines superior to ESC/EAS guidelines for primary prevention with statins in non-diabetic Europeans: the Copenhagen General Population Study.

PubMed

Mortensen, Martin Bødtker; Nordestgaard, Børge G; Afzal, Shoaib; Falk, Erling

2017-02-21

We compared the 2013 American College of Cardiology/American Heart Association (ACC/AHA) and the 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines on prevention of atherosclerotic cardiovascular disease (ASCVD) using different risk prediction models [US Pooled Cohort Equations (US-PCE for any ASCVD) and European Systematic COronary Risk Evaluation system (European-SCORE for fatal ASCVD)] and different statin eligibility criteria. We examined 44 889 individuals aged 40-75 recruited in 2003-09 in the Copenhagen General Population Study, all free of ASCVD, diabetes, and statin use at baseline. We detected 2217 any ASCVD events and 199 fatal ASCVD events through 2014. The predicted-to-observed event ratio was 1.2 using US-PCE for any ASCVD and 5.0 using European-SCORE for fatal ASCVD. The US-PCE, but not the European-SCORE, was well-calibrated around decision thresholds for statin therapy. For a Class I recommendation, 42% of individuals qualified for statins using the ACC/AHA guidelines vs. 6% with the ESC/EAS guidelines. Using ACC/AHA- vs. ESC/EAS-defined statin eligibility led to a substantial gain in sensitivity (+62% for any ASCVD and +76% for fatal ASCVD) with a smaller loss in specificity (-35% for any ASCVD and -36% for fatal ASCVD). Similar differences between the ACC/AHA and ESC/EAS guidelines were found for men and women separately, and for Class IIa recommendations. The sensitivity and specificity of a US-PCE risk of 5% were similar to those of a European-SCORE risk of 1.4%, whereas a US-PCE risk of 7.5% was similar to a European-SCORE risk of 2.4%. The ACC/AHA guidelines were superior to the ESC/EAS guidelines for primary prevention of ASCVD, that is, for accurately assigning statin therapy to those who would benefit. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology

ACC/AHA guidelines superior to ESC/EAS guidelines for primary prevention with statins in non-diabetic Europeans: the Copenhagen General Population Study

PubMed Central

Mortensen, Martin Bødtker; Nordestgaard, Børge G.; Afzal, Shoaib; Falk, Erling

2017-01-01

Abstract Aim We compared the 2013 American College of Cardiology/American Heart Association (ACC/AHA) and the 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines on prevention of atherosclerotic cardiovascular disease (ASCVD) using different risk prediction models [US Pooled Cohort Equations (US-PCE for any ASCVD) and European Systematic COronary Risk Evaluation system (European-SCORE for fatal ASCVD)] and different statin eligibility criteria. Methods and results We examined 44 889 individuals aged 40–75 recruited in 2003–09 in the Copenhagen General Population Study, all free of ASCVD, diabetes, and statin use at baseline. We detected 2217 any ASCVD events and 199 fatal ASCVD events through 2014. The predicted-to-observed event ratio was 1.2 using US-PCE for any ASCVD and 5.0 using European-SCORE for fatal ASCVD. The US-PCE, but not the European-SCORE, was well-calibrated around decision thresholds for statin therapy. For a Class I recommendation, 42% of individuals qualified for statins using the ACC/AHA guidelines vs. 6% with the ESC/EAS guidelines. Using ACC/AHA- vs. ESC/EAS-defined statin eligibility led to a substantial gain in sensitivity (+62% for any ASCVD and +76% for fatal ASCVD) with a smaller loss in specificity (−35% for any ASCVD and −36% for fatal ASCVD). Similar differences between the ACC/AHA and ESC/EAS guidelines were found for men and women separately, and for Class IIa recommendations. The sensitivity and specificity of a US-PCE risk of 5% were similar to those of a European-SCORE risk of 1.4%, whereas a US-PCE risk of 7.5% was similar to a European-SCORE risk of 2.4%. Conclusions The ACC/AHA guidelines were superior to the ESC/EAS guidelines for primary prevention of ASCVD, that is, for accurately assigning statin therapy to those who would benefit. PMID:28363217

Risk prediction and aversion by anterior cingulate cortex.

PubMed

Brown, Joshua W; Braver, Todd S

2007-12-01

The recently proposed error-likelihood hypothesis suggests that anterior cingulate cortex (ACC) and surrounding areas will become active in proportion to the perceived likelihood of an error. The hypothesis was originally derived from a computational model prediction. The same computational model now makes a further prediction that ACC will be sensitive not only to predicted error likelihood, but also to the predicted magnitude of the consequences, should an error occur. The product of error likelihood and predicted error consequence magnitude collectively defines the general "expected risk" of a given behavior in a manner analogous but orthogonal to subjective expected utility theory. New fMRI results from an incentivechange signal task now replicate the error-likelihood effect, validate the further predictions of the computational model, and suggest why some segments of the population may fail to show an error-likelihood effect. In particular, error-likelihood effects and expected risk effects in general indicate greater sensitivity to earlier predictors of errors and are seen in risk-averse but not risk-tolerant individuals. Taken together, the results are consistent with an expected risk model of ACC and suggest that ACC may generally contribute to cognitive control by recruiting brain activity to avoid risk.

A randomized trial of assertive continuing care and contingency management for adolescents with substance use disorders.

PubMed

Godley, Mark D; Godley, Susan H; Dennis, Michael L; Funk, Rodney R; Passetti, Lora L; Petry, Nancy M

2014-02-01

Most adolescents relapse within 90 days of discharge from residential substance use treatment. We hypothesized that contingency management (CM), assertive continuing care (ACC), and their combination (CM + ACC) would each be more effective than usual continuing care (UCC). Following residential treatment, 337 adolescents were randomized to 4 continuing care conditions: UCC alone, CM, ACC, or CM + ACC. UCC was available across all conditions. Outcome measures over 12 months included percentage of days abstinent from alcohol, heavy alcohol, marijuana, and any alcohol or other drugs (AOD) using self-reports and toxicology testing and remission status at 12 months. CM had significantly higher rates of abstinence than UCC for heavy alcohol use, t(297) = 2.50, p < .01, d = 0.34; any alcohol use, t(297) = 2.58, p < .01, d = 0.36; or any AOD use, t(297) = 2.12, p = .01, d = 0.41; and had a higher rate in remission, odds ratio (OR) = 2.45, 90% confidence interval (CI) [1.18, 5.08], p = .02. ACC had significantly higher rates of abstinence than UCC from heavy alcohol use, t(297) = 2.66, p < .01, d = 0.31; any alcohol use, t(297) = 2.63, p < .01, d = 0.30; any marijuana use, t(297) = 1.95, p = .02, d = 0.28; or any AOD use, t(297) = 1.88, p = .02, d = 0.30; and had higher rates in remission, OR = 2.31, 90% CI [1.10, 4.85], p = .03. The ACC + CM condition was not significantly different from UCC on any outcomes. CM and ACC are promising continuing care approaches after residential treatment. Future research should seek to further improve their effectiveness. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Modelling brain activations and connectivity of pain modulated by having a loved one nearby

NASA Astrophysics Data System (ADS)

Tamam, Sofina; Ahmad, Asma Hayati; Kamil, Wan Ahmad

2018-06-01

This study is to model the connectivity between activated areas in the brain associated with pain responses in the presence and absence of a loved one. We used Th:YAG laser targeted onto the dorsum of the right hand of 17 Malay-female participants (mean age 20.59; SD 2.85 years) in two conditions: (1) in the absence of a loved one in the functional magnetic resonance imaging (fMRI) room (Alone condition), and (2) in the presence of a loved one (Support condition). The laser-induced pain stimuli were delivered according to an fMRI paradigm utilising blocked design comprising 15 blocks of activity and 15 blocks of rest. Brain activations and connectivity were analysed using statistical parametric mapping (SPM), dynamic causal modelling (DCM) and Bayesian model selection (BMS) analyses. Individual responses to pain were found to be divided into two categories: (1) Love Hurts (participants who reported more pain in the presence of a loved one) involved activations in thalamus (THA), parahippocampal gyrus (PHG) and hippocampus (HIP); and (2) Love Heals (participants who reported less pain in the presence of a loved one) involved activations in all parts of cingulate cortex. BMS showed that Love Heals could be represented by a cortical network involving the area of anterior cingulate cortex (ACC), middle cingulate cortex (MCC) and posterior cingulate cortex (PCC) in the intrinsic connectivity of ACC → PCC → MCC and ACC → MCC. There was no optimal model to explain the increase in pain threshold when accompanied by the loved one in Love Hurts. The present study reveals a new possible cortical network for the reduction of pain by having a loved one nearby.

Human Identification by Cross-Correlation and Pattern Matching of Personalized Heartbeat: Influence of ECG Leads and Reference Database Size.

PubMed

Jekova, Irena; Krasteva, Vessela; Schmid, Ramun

2018-01-27

Human identification (ID) is a biometric task, comparing single input sample to many stored templates to identify an individual in a reference database. This paper aims to present the perspectives of personalized heartbeat pattern for reliable ECG-based identification. The investigations are using a database with 460 pairs of 12-lead resting electrocardiograms (ECG) with 10-s durations recorded at time-instants T1 and T2 > T1 + 1 year. Intra-subject long-term ECG stability and inter-subject variability of personalized PQRST (500 ms) and QRS (100 ms) patterns is quantified via cross-correlation, amplitude ratio and pattern matching between T1 and T2 using 7 features × 12-leads. Single and multi-lead ID models are trained on the first 230 ECG pairs. Their validation on 10, 20, ... 230 reference subjects (RS) from the remaining 230 ECG pairs shows: (i) two best single-lead ID models using lead II for a small population RS = (10-140) with identification accuracy AccID = (89.4-67.2)% and aVF for a large population RS = (140-230) with AccID = (67.2-63.9)%; (ii) better performance of the 6-lead limb vs. the 6-lead chest ID model-(91.4-76.1)% vs. (90.9-70)% for RS = (10-230); (iii) best performance of the 12-lead ID model-(98.4-87.4)% for RS = (10-230). The tolerable reference database size, keeping AccID > 80%, is RS = 30 in the single-lead ID scenario (II); RS = 50 (6 chest leads); RS = 100 (6 limb leads), RS > 230-maximal population in this study (12-lead ECG).

Targeting the Oncogenic Transcriptional Regulator MYB in Adenoid Cystic Carcinoma by Inhibition of IGF1R/AKT Signaling.

PubMed

Andersson, Mattias K; Afshari, Maryam K; Andrén, Ywonne; Wick, Michael J; Stenman, Göran

2017-09-01

Adenoid cystic carcinoma (ACC) is an aggressive cancer with no curative treatment for patients with recurrent/metastatic disease. The MYB-NFIB gene fusion is the main genomic hallmark and a potential therapeutic target. Oncogenic signaling pathways were studied in cultured cells and/or tumors from 15 ACC patients. Phospho-receptor tyrosine kinase (RTK) arrays were used to study the activity of RTKs. Effects of RTK inhibition on cell proliferation were analyzed with AlamarBlue, sphere assays, and two ACC xenograft models (n = 4-9 mice per group). The molecular effects of MYB-NFIB knockdown and IGF1R inhibition were studied with quantitative polymerase chain reaction, immunoblot, and gene expression microarrays. All statistical tests were two-sided. The MYB-NFIB fusion drives proliferation of ACC cells and is crucial for spherogenesis. Intriguingly, the fusion is regulated through AKT-dependent signaling induced by IGF1R overexpression and is downregulated upon IGF1R-inhibition (% expression of control ± SD = 27.2 ± 1.3, P < .001). MYB-NFIB regulates genes involved in cell cycle control, DNA replication/repair, and RNA processing. The transcriptional program induced by MYB-NFIB affects critical oncogenic mediators normally controlled by MYC and is reversed by pharmacological inhibition of IGF1R. Co-activation of epidermal growth factor receptor (EGFR) and MET promoted proliferation of ACC cells, and combined targeting of IGFR1/EGFR/MET induced differentiation and synergistically inhibited the growth of patient-derived xenografted ACCs (ACCX5M1, % growth of control ± SD = 34.9 ± 20.3, P = .006; ACCX6, % growth of control ± SD = 24.1 ± 17.5, P = .04). MYB-NFIB is an oncogenic driver and a key therapeutic target in ACC that is regulated by AKT-dependent IGF1R signaling. Our studies uncover a new strategy to target an oncogenic transcriptional master regulator and provide new important insights into the biology and treatment of ACC. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Improved Mars Upper Atmosphere Climatology

NASA Technical Reports Server (NTRS)

Bougher, S. W.

2004-01-01

The detailed characterization of the Mars upper atmosphere is important for future Mars aerobraking activities. Solar cycle, seasonal, and dust trends (climate) as well as planetary wave activity (weather) are crucial to quantify in order to improve our ability to reasonably depict the state of the Mars upper atmosphere over time. To date, our best information is found in the Mars Global Surveyor (MGS) Accelerometer (ACC) database collected during Phase 1 (Ls = 184 - 300; F10.7 = 70 - 90) and Phase 2 (Ls = 30 - 90; F10.7 = 90 - 150) of aerobraking. This database (100 - 170 km) consists of thermospheric densities, temperatures, and scale heights, providing our best constraints for exercising the coupled Mars General Circulation Model (MGCM) and the Mars Thermospheric General Circulation Model (MTGCM). The Planetary Data System (PDS) contains level 0 and 2 MGS Accelerometer data, corresponding to atmospheric densities along the orbit track. Level 3 products (densities, temperatures, and scale heights at constant altitudes) are also available in the PDS. These datasets provide the primary model constraints for the new MGCM-MTGCM simulations summarized in this report. Our strategy for improving the characterization of the Mars upper atmospheres using these models has been three-fold : (a) to conduct data-model comparisons using the latest MGS data covering limited climatic and weather conditions at Mars, (b) to upgrade the 15-micron cooling and near-IR heating rates in the MGCM and MTGCM codes for ad- dressing climatic variations (solar cycle and seasonal) important in linking the lower and upper atmospheres (including migrating tides), and (c) to exercise the detailed coupled MGCM and MTGCM codes to capture and diagnose the planetary wave (migrating plus non-migrating tidal) features throughout the Mars year. Products from this new suite of MGCM-MTGCM coupled simulations are being used to improve our predictions of the structure of the Mars upper atmosphere for the upcoming MRO aerobraking exercises in 2006. A Michigan website, containing MTGCM output fields from previous climate simulations, is being expanded to include new MGCM-MTGCM simulations addressing planetary wave influences upon thermospheric aerobraking fields (densities and temperatures). In addition, similar MTGCM output fields have been supplied to the MSFC MARSGRAM - 200X empirical model, which will be used in mission operations for conducting aerobraking maneuvers.

Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intake

PubMed Central

Gao, Su; Kinzig, Kimberly P.; Aja, Susan; Scott, Karen A.; Keung, Wendy; Kelly, Sandra; Strynadka, Ken; Chohnan, Shigeru; Smith, Wanli W.; Tamashiro, Kellie L. K.; Ladenheim, Ellen E.; Ronnett, Gabriele V.; Tu, Yajun; Birnbaum, Morris J.; Lopaschuk, Gary D.; Moran, Timothy H.

2007-01-01

Hypothalamic fatty acid metabolism has recently been implicated in the controls of food intake and energy homeostasis. We report that intracerebroventricular (ICV) injection of leptin, concomitant with inhibiting AMP-activated kinase (AMPK), activates acetyl-CoA carboxylase (ACC), the key regulatory enzyme in fatty acid biosynthesis, in the arcuate nucleus (Arc) and paraventricular nucleus (PVN) in the hypothalamus. Arc overexpression of constitutively active AMPK prevents the Arc ACC activation in response to ICV leptin, supporting the hypothesis that AMPK lies upstream of ACC in leptin's Arc intracellular signaling pathway. Inhibiting hypothalamic ACC with 5-tetradecyloxy-2-furoic acid, a specific ACC inhibitor, blocks leptin-mediated decreases in food intake, body weight, and mRNA level of the orexigenic neuropeptide NPY. These results show that hypothalamic ACC activation makes an important contribution to leptin's anorectic effects. Furthermore, we find that ICV leptin up-regulates the level of malonyl-CoA (the intermediate of fatty acid biosynthesis) specifically in the Arc and increases the level of palmitoyl-CoA (a major product of fatty acid biosynthesis) specifically in the PVN. The rises of both levels are blocked by 5-tetradecyloxy-2-furoic acid along with the blockade of leptin-mediated hypophagia. These data suggest malonyl-CoA as a downstream mediator of ACC in leptin's signaling pathway in the Arc and imply that palmitoyl-CoA, instead of malonyl-CoA, could be an effector in relaying ACC signaling in the PVN. Together, these findings highlight site-specific impacts of hypothalamic ACC activation in leptin's anorectic signaling cascade. PMID:17956983

The Allende multicompound chondrule (ACC)—Chondrule formation in a local super-dense region of the early solar system

NASA Astrophysics Data System (ADS)

Bischoff, Addi; Wurm, Gerhard; Chaussidon, Marc; Horstmann, Marian; Metzler, Knut; Weyrauch, Mona; Weinauer, Julia

2017-05-01

In Allende, a very complex compound chondrule (Allende compound chondrule; ACC) was found consisting of at least 16 subchondrules (14 siblings and 2 independents). Its overall texture can roughly be described as a barred olivine object (BO). The BO texture is similar in all siblings, but does not exist in the two independents, which appear as relatively compact olivine-rich units. Because of secondary alteration of pristine Allende components and the ACC in particular, only limited predictions can be made concerning the original compositions of the colliding melt droplets. Based on textural and mineralogical characteristics, the siblings must have been formed on a very short time scale in a dense, local environment. This is also supported by oxygen isotope systematics showing similar compositions for all 16 subchondrules. Furthermore, the ACC subchondrules are isotopically distinct from typical Allende chondrules, indicating formation in or reaction with a more 16O-poor reservoir. We modeled constraints on the particle density required at the ACC formation location, using textural, mineral-chemical, and isotopic observations on this multicompound chondrule to define melt droplet collision conditions. In this context, we discuss the possible relationship between the formation of complex chondrules and the formation of macrochondrules and cluster chondrites. While macrochondrules may have formed under similar or related conditions as complex chondrules, cluster chondrites certainly require different formation conditions. Cluster chondrites represent a mixture of viscously deformed, seemingly young chondrules of different chemical and textural types and a population of older chondrules. Concerning the formation of ACC calculations suggest the existence of very local, kilometer-sized, and super-dense chondrule-forming regions with extremely high solid-to-gas mass ratios of 1000 or more.

Competition between learned reward and error outcome predictions in anterior cingulate cortex.

PubMed

Alexander, William H; Brown, Joshua W

2010-02-15

The anterior cingulate cortex (ACC) is implicated in performance monitoring and cognitive control. Non-human primate studies of ACC show prominent reward signals, but these are elusive in human studies, which instead show mainly conflict and error effects. Here we demonstrate distinct appetitive and aversive activity in human ACC. The error likelihood hypothesis suggests that ACC activity increases in proportion to the likelihood of an error, and ACC is also sensitive to the consequence magnitude of the predicted error. Previous work further showed that error likelihood effects reach a ceiling as the potential consequences of an error increase, possibly due to reductions in the average reward. We explored this issue by independently manipulating reward magnitude of task responses and error likelihood while controlling for potential error consequences in an Incentive Change Signal Task. The fMRI results ruled out a modulatory effect of expected reward on error likelihood effects in favor of a competition effect between expected reward and error likelihood. Dynamic causal modeling showed that error likelihood and expected reward signals are intrinsic to the ACC rather than received from elsewhere. These findings agree with interpretations of ACC activity as signaling both perceptions of risk and predicted reward. Copyright 2009 Elsevier Inc. All rights reserved.

Modelling the cost-effectiveness of pharmacist-managed anticoagulation service for older adults with atrial fibrillation in Singapore.

PubMed

Chua, Wen Bing Brandon; Cheen, Hua Heng McVin; Kong, Ming Chai; Chen, Li Li; Wee, Hwee Lin

2016-10-01

Background Oral anticoagulation with warfarin is the cornerstone therapy in atrial fibrillation (AF) for stroke prevention. Multi-disciplinary anticoagulation management services have been shown to be cost-effective in the United States, Hong Kong and Thailand, but the findings are not readily generalizable to Singapore's healthcare system. Objective This study aimed to evaluate the cost-effectiveness of pharmacist-managed anticoagulation clinic (ACC) compared with usual care (UC) for the management of older adults with AF receiving oral anticoagulation with warfarin. Setting Pharmacist-managed ACC in an academic medical centre. Method A Markov model with 3-month cycle length and 30-year time horizon compared costs and quality-adjusted life-years (QALYs) of ACC and UC from the patient's and healthcare provider's perspectives. Four pathways based on time in therapeutic range (TTR) were: ACC TTR < 70 %, ACC TTR ≥ 70 %, UC TTR < 70 % and UC TTR ≥ 70 %. A hypothetical cohort of 70-year-old Singaporean AF patients receiving warfarin was utilised. Local data from national disease registries, patient surveys and hospital databases were used. When local data was not available, published studies on Asian populations were utilized when available. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to account for uncertainties. Costs and QALYs were discounted annually by 3 %. Main outcome measure Costs and QALYs of ACC and UC. Results Pharmacist-managed ACC was found to dominate UC in all comparisons. It improved effectiveness by 0.19 and 0.13 QALYs at TTR < 70 % and TTR ≥ 70 % respectively compared with UC. From the patient's perspective, ACC reduced costs by SG$1222.67 (€1110.24) for TTR < 70 % and SG$1008.16 (€915.46) for TTR ≥ 70 %. Similar trends were observed from the healthcare provider's perspective, with ACC reducing costs by SG$1444.79 (€1311.94) for TTR < 70 % and SG$1269.17 (€1152.46) for TTR ≥ 70 % compared with UC. The results were robust to variations of the parameters over their plausible ranges in one-way sensitivity analyses. Probabilistic sensitivity analyses demonstrated that ACC was cost-effective more than 79 % of the time from both perspectives at a willingness-to-pay threshold of SG$69,050 (€62,701) per QALY. Conclusion Pharmacist-managed ACC is more effective and less costly compared with UC regardless of the quality of anticoagulation therapy. The findings support the current body of evidence demonstrating the cost-effectiveness of ACC.

Glacial reduction and millennial-scale variations in Drake Passage throughflow.

PubMed

Lamy, Frank; Arz, Helge W; Kilian, Rolf; Lange, Carina B; Lembke-Jene, Lester; Wengler, Marc; Kaiser, Jérôme; Baeza-Urrea, Oscar; Hall, Ian R; Harada, Naomi; Tiedemann, Ralf

2015-11-03

The Drake Passage (DP) is the major geographic constriction for the Antarctic Circumpolar Current (ACC) and exerts a strong control on the exchange of physical, chemical, and biological properties between the Atlantic, Pacific, and Indian Ocean basins. Resolving changes in the flow of circumpolar water masses through this gateway is, therefore, crucial for advancing our understanding of the Southern Ocean's role in global ocean and climate variability. Here, we reconstruct changes in DP throughflow dynamics over the past 65,000 y based on grain size and geochemical properties of sediment records from the southernmost continental margin of South America. Combined with published sediment records from the Scotia Sea, we argue for a considerable total reduction of DP transport and reveal an up to ∼ 40% decrease in flow speed along the northernmost ACC pathway entering the DP during glacial times. Superimposed on this long-term decrease are high-amplitude, millennial-scale variations, which parallel Southern Ocean and Antarctic temperature patterns. The glacial intervals of strong weakening of the ACC entering the DP imply an enhanced export of northern ACC surface and intermediate waters into the South Pacific Gyre and reduced Pacific-Atlantic exchange through the DP ("cold water route"). We conclude that changes in DP throughflow play a critical role for the global meridional overturning circulation and interbasin exchange in the Southern Ocean, most likely regulated by variations in the westerly wind field and changes in Antarctic sea ice extent.

Glacial reduction and millennial-scale variations in Drake Passage throughflow

PubMed Central

Lamy, Frank; Arz, Helge W.; Kilian, Rolf; Lange, Carina B.; Lembke-Jene, Lester; Wengler, Marc; Kaiser, Jérôme; Baeza-Urrea, Oscar; Hall, Ian R.; Harada, Naomi; Tiedemann, Ralf

2015-01-01

The Drake Passage (DP) is the major geographic constriction for the Antarctic Circumpolar Current (ACC) and exerts a strong control on the exchange of physical, chemical, and biological properties between the Atlantic, Pacific, and Indian Ocean basins. Resolving changes in the flow of circumpolar water masses through this gateway is, therefore, crucial for advancing our understanding of the Southern Ocean’s role in global ocean and climate variability. Here, we reconstruct changes in DP throughflow dynamics over the past 65,000 y based on grain size and geochemical properties of sediment records from the southernmost continental margin of South America. Combined with published sediment records from the Scotia Sea, we argue for a considerable total reduction of DP transport and reveal an up to ∼40% decrease in flow speed along the northernmost ACC pathway entering the DP during glacial times. Superimposed on this long-term decrease are high-amplitude, millennial-scale variations, which parallel Southern Ocean and Antarctic temperature patterns. The glacial intervals of strong weakening of the ACC entering the DP imply an enhanced export of northern ACC surface and intermediate waters into the South Pacific Gyre and reduced Pacific–Atlantic exchange through the DP (“cold water route”). We conclude that changes in DP throughflow play a critical role for the global meridional overturning circulation and interbasin exchange in the Southern Ocean, most likely regulated by variations in the westerly wind field and changes in Antarctic sea ice extent. PMID:26417070

Baleen boom and bust: a synthesis of mysticete phylogeny, diversity and disparity

PubMed Central

Marx, Felix G.; Fordyce, R. Ewan

2015-01-01

A new, fully dated total-evidence phylogeny of baleen whales (Mysticeti) shows that evolutionary phases correlate strongly with Caenozoic modernization of the oceans and climates, implying a major role for bottom-up physical drivers. The phylogeny of 90 modern and dated fossil species suggests three major phases in baleen whale history: an early adaptive radiation (36–30 Ma), a shift towards bulk filter-feeding (30–23 Ma) and a climate-driven diversity loss around 3 Ma. Evolutionary rates and disparity were high following the origin of mysticetes around 38 Ma, coincident with global cooling, abrupt Southern Ocean eutrophication and the development of the Antarctic Circumpolar Current (ACC). Subsequently, evolutionary rates and disparity fell, becoming nearly constant after approximately 23 Ma as the ACC reached its full strength. By contrast, species diversity rose until 15 Ma and then remained stable, before dropping sharply with the onset of Northern Hemisphere glaciation. This decline coincided with the final establishment of modern mysticete gigantism and may be linked to glacially driven variability in the distribution of shallow habitats or an increased need for long-distance migration related to iron-mediated changes in glacial marine productivity. PMID:26064636

Baleen boom and bust: a synthesis of mysticete phylogeny, diversity and disparity.

PubMed

Marx, Felix G; Fordyce, R Ewan

2015-04-01

A new, fully dated total-evidence phylogeny of baleen whales (Mysticeti) shows that evolutionary phases correlate strongly with Caenozoic modernization of the oceans and climates, implying a major role for bottom-up physical drivers. The phylogeny of 90 modern and dated fossil species suggests three major phases in baleen whale history: an early adaptive radiation (36-30 Ma), a shift towards bulk filter-feeding (30-23 Ma) and a climate-driven diversity loss around 3 Ma. Evolutionary rates and disparity were high following the origin of mysticetes around 38 Ma, coincident with global cooling, abrupt Southern Ocean eutrophication and the development of the Antarctic Circumpolar Current (ACC). Subsequently, evolutionary rates and disparity fell, becoming nearly constant after approximately 23 Ma as the ACC reached its full strength. By contrast, species diversity rose until 15 Ma and then remained stable, before dropping sharply with the onset of Northern Hemisphere glaciation. This decline coincided with the final establishment of modern mysticete gigantism and may be linked to glacially driven variability in the distribution of shallow habitats or an increased need for long-distance migration related to iron-mediated changes in glacial marine productivity.

Portable LQCD Monte Carlo code using OpenACC

NASA Astrophysics Data System (ADS)

Bonati, Claudio; Calore, Enrico; Coscetti, Simone; D'Elia, Massimo; Mesiti, Michele; Negro, Francesco; Fabio Schifano, Sebastiano; Silvi, Giorgio; Tripiccione, Raffaele

2018-03-01

Varying from multi-core CPU processors to many-core GPUs, the present scenario of HPC architectures is extremely heterogeneous. In this context, code portability is increasingly important for easy maintainability of applications; this is relevant in scientific computing where code changes are numerous and frequent. In this talk we present the design and optimization of a state-of-the-art production level LQCD Monte Carlo application, using the OpenACC directives model. OpenACC aims to abstract parallel programming to a descriptive level, where programmers do not need to specify the mapping of the code on the target machine. We describe the OpenACC implementation and show that the same code is able to target different architectures, including state-of-the-art CPUs and GPUs.

Acetyl-CoA carboxylase rewires cancer metabolism to allow cancer cells to survive inhibition of the Warburg effect by cetuximab

PubMed Central

Luo, Jingtao; Hong, Yun; Lu, Yang; Qiu, Songbo; Chaganty, Bharat K. R.; Zhang, Lun; Wang, Xudong; Li, Qiang; Fan, Zhen

2016-01-01

Cetuximab inhibits HIF-1-regulated glycolysis in cancer cells, thereby reversing the Warburg effect and leading to inhibition of cancer cell metabolism. AMP-activated protein kinase (AMPK) is activated after cetuximab treatment, and a sustained AMPK activity is a mechanism contributing to cetuximab resistance. Here, we investigated how acetyl-CoA carboxylase (ACC), a downstream target of AMPK, rewires cancer metabolism in response to cetuximab treatment. We found that introduction of experimental ACC mutants lacking the AMPK phosphorylation sites (ACC1_S79A and ACC2_S212A) into head and neck squamous cell carcinoma (HNSCC) cells protected HNSCC cells from cetuximab-induced growth inhibition. HNSCC cells with acquired cetuximab resistance contained not only high levels of T172-phosphorylated AMPK and S79-phosphorylated ACC1 but also an increased level of total ACC. These findings were corroborated in tumor specimens of HNSCC patients treated with cetuximab. Cetuximab plus TOFA (an allosteric inhibitor of ACC) achieved remarkable growth inhibition of cetuximab-resistant HNSCC xenografts. Our data suggest a novel paradigm in which cetuximab-mediated activation of AMPK and subsequent phosphorylation and inhibition of ACC is followed by a compensatory increase in total ACC, which rewires cancer metabolism from glycolysis-dependent to lipogenesis-dependent. PMID:27693630

Performance, throughput, and cost of in-home training for the Army Reserve: Using asynchronous computer conferencing as an alternative to resident training

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hahn, H.A.; Ashworth, R.L. Jr.; Phelps, R.H.

1990-01-01

Asynchronous computer conferencing (ACC) was investigated as an alternative to resident training for the Army Reserve Component (RC). Specifically, the goals were to (1) evaluate the performance and throughput of ACC as compared with traditional Resident School instruction and (2) determine the cost-effectiveness of developing and implementing ACC. Fourteen RC students took a module of the Army Engineer Officer Advanced Course (EOAC) via ACC. Course topics included Army doctrine, technical engineering subjects, leadership, and presentation skills. Resident content was adapted for presentation via ACC. The programs of instruction for ACC and the equivalent resident course were identical; only the mediamore » used for presentation were changed. Performance on tests, homework, and practical exercises; self-assessments of learning; throughput; and cost data wee the measures of interest. Comparison data were collected on RC students taking the course in residence. Results indicated that there were no performance differences between the two groups. Students taking the course via ACC perceived greater learning benefit than did students taking the course in residence. Resident throughput was superior to ACC throughput, both in terms of numbers of students completing and time to complete the course. In spite of this fact, however, ACC was more cost-effective than resident training.« less

24 CFR 883.604 - Maximum annual commitment and project account.

Code of Federal Regulations, 2011 CFR

2011-04-01

... annual commitment. The maximum annual contribution that may be contracted for in the ACC is the total of... annual commitment exceeds the amount actually paid out under the ACC each year. Payments will be made... specifically approved by the Secretary. (2) Whenever a HUD-approved estimate of required payments under the ACC...

24 CFR 883.604 - Maximum annual commitment and project account.

Code of Federal Regulations, 2010 CFR

2010-04-01

... annual commitment. The maximum annual contribution that may be contracted for in the ACC is the total of... annual commitment exceeds the amount actually paid out under the ACC each year. Payments will be made... specifically approved by the Secretary. (2) Whenever a HUD-approved estimate of required payments under the ACC...

Variable responses of two VlMYBA gene promoters to ABA and ACC in Kyoho grape berries.

PubMed

Zhai, Xiawan; Zhang, Yushu; Kai, Wenbin; Liang, Bin; Jiang, Li; Du, Yangwei; Wang, Juan; Sun, Yufei; Leng, Ping

2017-04-01

The VlMYBA subfamily of transcription factors has been known to be the functional regulators in anthocyanin biosynthesis in red grapes. In this study, the expressions of the VlMYBA1-2 and VlMYBA 2 genes, and the responses of the VlMYBA1-2/2 promoters to ABA and ACC treatments in Kyoho grape berries are examined through quantitative real-time PCR analysis and the transient expression assay. The results show that the expressions of VlMYBA1-2/2 increase dramatically after véraison and reach their highest levels when the berries are nearly fully ripe. Exogenous ABA promotes the expressions of VlMYBA1-2/2, whereas the ACC treatment increases the expression of VlMYBA2, however, it has no effect on VlMYBA1-2. The ABA treatment has a faster and stronger effect on berry pigmentation than ACC does. The VlMYBA1-2 promoter sequence contains two ABA response elements (ABRE) but no ethylene response element (ERE), whereas the VlMYBA2 promoter sequence contains two ABRE and one ERE in the upstream region of the start codon. The VlMYBA2 promoter can be activated by both ABA (more effective) and ACC, whereas the VlMYBA1-2 promoter can be activated by ABA only. In sum, ABA can promote the coloring of Kyoho grape by the promotion of VlMYBA1-2/2 transcriptions via activating the response of their promoters to ABA, whereas ethylene only regulates VlMYBA2 through the response activation of its promoter to ACC which partially enhances the coloring. Copyright © 2017 Elsevier GmbH. All rights reserved.

Abundance and diversity of archaeal accA gene in hot springs in Yunnan Province, China.

PubMed

Song, Zhao-Qi; Wang, Li; Wang, Feng-Ping; Jiang, Hong-Chen; Chen, Jin-Quan; Zhou, En-Min; Liang, Feng; Xiao, Xiang; Li, Wen-Jun

2013-09-01

It has been suggested that archaea carrying the accA gene, encoding the alpha subunit of the acetyl CoA carboxylase, autotrophically fix CO2 using the 3-hydroxypropionate/4-hydroxybutyrate pathway in low-temperature environments (e.g., soils, oceans). However, little new information has come to light regarding the occurrence of archaeal accA genes in high-temperature ecosystems. In this study, we investigated the abundance and diversity of archaeal accA gene in hot springs in Yunnan Province, China, using DNA- and RNA-based phylogenetic analyses and quantitative polymerase chain reaction. The results showed that archaeal accA genes were present and expressed in the investigated Yunnan hot springs with a wide range of temperatures (66-96 °C) and pH (4.3-9.0). The majority of the amplified archaeal accA gene sequences were affiliated with the ThAOA/HWCG III [thermophilic ammonia-oxidizing archaea (AOA)/hot water crenarchaeotic group III]. The archaeal accA gene abundance was very close to that of AOA amoA gene, encoding the alpha subunit of ammonia monooxygenase. These data suggest that AOA in terrestrial hot springs might acquire energy from ammonia oxidation coupled with CO2 fixation using the 3-hydroxypropionate/4-hydroxybutyrate pathway.

Marked phylogeographic structure of Gentoo penguin reveals an ongoing diversification process along the Southern Ocean.

PubMed

Vianna, Juliana A; Noll, Daly; Dantas, Gisele P M; Petry, Maria Virginia; Barbosa, Andrés; González-Acuña, Daniel; Le Bohec, Céline; Bonadonna, Francesco; Poulin, Elie

2017-02-01

Two main hypotheses have been debated about the biogeography of the Southern Ocean: (1) the Antarctic Polar Front (APF), acting as a barrier between Antarctic and sub-Antarctic provinces, and (2) the Antarctic Circumpolar Current (ACC), promoting gene flow among sub-Antarctic areas. The Gentoo penguin is distributed throughout these two provinces, separated by the APF. We analyzed mtDNA (HVR1) and 12 microsatellite loci of 264 Gentoo penguins, Pygoscelis papua, from 12 colonies spanning from the Western Antarctic Peninsula and the South Shetland Islands (WAP) to the sub-Antarctic Islands (SAI). While low genetic structure was detected among WAP colonies (mtDNA Ф ST =0.037-0.133; microsatellite F ST =0.009-0.063), high differentiation was found between all SAI and WAP populations (mtDNA Ф ST =0.678-0.930; microsatellite F ST =0.110-0.290). These results suggest that contemporary dispersal around the Southern Ocean is very limited or absent. As predicted, the APF appears to be a significant biogeographical boundary for Gentoo penguin populations; however, the ACC does not promote connectivity in this species. Our data suggest demographic expansion in the WAP during the last glacial maximum (LGM, about 20kya), but stability in SAI. Phylogenetic analyses showed a deep divergence between populations from the WAP and those from the SAI. Therefore, taxonomy should be further revised. The Crozet Islands resulted as a basal clade (3.57Mya), followed by the Kerguelen Islands (2.32Mya) as well as a more recent divergence between the Falkland/Malvinas Islands and the WAP (1.27Mya). Historical isolation, local adaptation, and past climate scenarios of those Evolutionarily Significant Units may have led to different potentials to respond to climate changes. Copyright © 2016 Elsevier Inc. All rights reserved.

Further studies of auxin and ACC induced feminization in the cucumber plant using ethylene inhibitors

NASA Technical Reports Server (NTRS)

Takahashi, H.; Jaffe, M. J.

1984-01-01

The present study was designed to establish the role of an essential hormone controlling sex expression in cucumber. A potent anti-ethylene agent, AgNO3, completely inhibited pistillate flower formation caused by IAA, ACC or ethephon. Inhibitors of ethylene biosynthesis, AVG and CoCl2 also suppressed feminization due to exogenous IAA or ACC. Though AVG also suppressed ethephon-induced feminization, this may be due to the second effect of AVG rather than the effect on ACC biosynthesis. These results confirm that ethylene is a major factor regulating feminization and that exogenous auxin induces pistillate flower formation through its stimulation of ethylene production, rather than ACC production.

Deficient reinforcement learning in medial frontal cortex as a model of dopamine-related motivational deficits in ADHD.

PubMed

Silvetti, Massimo; Wiersema, Jan R; Sonuga-Barke, Edmund; Verguts, Tom

2013-10-01

Attention Deficit/Hyperactivity Disorder (ADHD) is a pathophysiologically complex and heterogeneous condition with both cognitive and motivational components. We propose a novel computational hypothesis of motivational deficits in ADHD, drawing together recent evidence on the role of anterior cingulate cortex (ACC) and associated mesolimbic dopamine circuits in both reinforcement learning and ADHD. Based on findings of dopamine dysregulation and ACC involvement in ADHD we simulated a lesion in a previously validated computational model of ACC (Reward Value and Prediction Model, RVPM). We explored the effects of the lesion on the processing of reinforcement signals. We tested specific behavioral predictions about the profile of reinforcement-related deficits in ADHD in three experimental contexts; probability tracking task, partial and continuous reward schedules, and immediate versus delayed rewards. In addition, predictions were made at the neurophysiological level. Behavioral and neurophysiological predictions from the RVPM-based lesion-model of motivational dysfunction in ADHD were confirmed by data from previously published studies. RVPM represents a promising model of ADHD reinforcement learning suggesting that ACC dysregulation might play a role in the pathogenesis of motivational deficits in ADHD. However, more behavioral and neurophysiological studies are required to test core predictions of the model. In addition, the interaction with different brain networks underpinning other aspects of ADHD neuropathology (i.e., executive function) needs to be better understood. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparative study of the Aristotle Comprehensive Complexity and the Risk Adjustment in Congenital Heart Surgery scores.

PubMed

Bojan, Mirela; Gerelli, Sébastien; Gioanni, Simone; Pouard, Philippe; Vouhé, Pascal

2011-09-01

The Aristotle Comprehensive Complexity (ACC) and the Risk Adjustment in Congenital Heart Surgery (RACHS-1) scores have been proposed for complexity adjustment in the analysis of outcome after congenital heart surgery. Previous studies found RACHS-1 to be a better predictor of outcome than the Aristotle Basic Complexity score. We compared the ability to predict operative mortality and morbidity between ACC, the latest update of the Aristotle method and RACHS-1. Morbidity was assessed by length of intensive care unit stay. We retrospectively enrolled patients undergoing congenital heart surgery. We modeled each score as a continuous variable, mortality as a binary variable, and length of stay as a censored variable. We compared performance between mortality and morbidity models using likelihood ratio tests for nested models and paired concordance statistics. Among all 1,384 patients enrolled, 30-day mortality rate was 3.5% and median length of intensive care unit stay was 3 days. Both scores strongly related to mortality, but ACC made better prediction than RACHS-1; c-indexes 0.87 (0.84, 0.91) vs 0.75 (0.65, 0.82). Both scores related to overall length of stay only during the first postoperative week, but ACC made better predictions than RACHS-1; U statistic=0.22, p<0.001. No significant difference was noted after adjusting RACHS-1 models on age, prematurity, and major extracardiac abnormalities. The ACC was a better predictor of operative mortality and length of intensive care unit stay than RACHS-1. In order to achieve similar performance, regression models including RACHS-1 need to be further adjusted on age, prematurity, and major extracardiac abnormalities. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Brain-derived neurotrophic factor (BDNF) in the rostral anterior cingulate cortex (rACC) contributes to neuropathic spontaneous pain-related aversion via NR2B receptors.

PubMed

Zhang, Le; Wang, Gongming; Ma, Jinben; Liu, Chengxiao; Liu, Xijiang; Zhan, Yufeng; Zhang, Mengyuan

2016-10-01

The rostral anterior cingulate cortex (rACC) plays an important role in pain affect. Previous investigations have reported that the rACC mediates the negative affective component of inflammatory pain and contributed to the aversive state of nerve injury-induced neuropathic pain. Brain-derived neurotrophic factor (BDNF), an activity-dependent neuromodulator in the adult brain, is believed to play a role in the development and maintenance of inflammatory and neuropathic pain in the spinal cord. However, whether and how BDNF in the rACC regulates pain-related aversion due to peripheral nerve injury is largely unknown. Behaviorally, using conditioned place preference (CPP) training in rats, which is thought to reveal spontaneous pain-related aversion, we found that CPP was acquired following spinal clonidine in rats with partial sciatic nerve transection. Importantly, BDNF was upregulated within the rACC in of rats with nerve injury and enhanced the CPP acquisition, while a local injection of a BDNF-tropomyosin receptor kinase B (TrkB) antagonist into the rACC completely blocked this process. Finally, we demonstrated that the BDNF/TrkB pathway exerted its function by activating the NR2B receptor, which is widely accepted to be a crucial factor contributing to pain affect. In conclusion, our results demonstrate that the BDNF/TrkB-mediated signaling pathway in the rACC is involved in the development of neuropathic spontaneous pain-related aversion and that this process is dependent upon activation of NR2B receptors. These findings suggest that suppression of the BDNF-related signaling pathway in the rACC may provide a novel strategy to overcome pain-related aversion. Copyright © 2016 Elsevier Inc. All rights reserved.

1-Aminocyclopropane-1-carboxylic acid oxidase reaction mechanism and putative post-translational activities of the ACCO protein

PubMed Central

Dilley, David R.; Wang, Zhenyong; Kadirjan-Kalbach, Deena K.; Ververidis, Fillipos; Beaudry, Randolph; Padmanabhan, Kallaithe

2013-01-01

1-Aminocyclopropane-1-carboxylic acid (ACC) oxidase (ACCO) catalyses the final step in ethylene biosynthesis converting ACC to ethylene, cyanide, CO2, dehydroascorbate and water with inputs of Fe(II), ascorbate, bicarbonate (as activators) and oxygen. Cyanide activates ACCO. A ‘nest’ comprising several positively charged amino acid residues from the C-terminal α-helix 11 along with Lys158 and Arg299 are proposed as binding sites for ascorbate and bicarbonate to coordinately activate the ACCO reaction. The binding sites for ACC, bicarbonate and ascorbic acid for Malus domestica ACCO1 include Arg175, Arg244, Ser246, Lys158, Lys292, Arg299 and Phe300. Glutamate 297, Phe300 and Glu301 in α-helix 11 are also important for the ACCO reaction. Our proposed reaction pathway incorporates cyanide as an ACCO/Fe(II) ligand after reaction turnover. The cyanide ligand is likely displaced upon binding of ACC and ascorbate to provide a binding site for oxygen. We propose that ACCO may be involved in the ethylene signal transduction pathway not directly linked to the ACCO reaction. ACC oxidase has significant homology with Lycopersicon esculentum cysteine protease LeCp, which functions as a protease and as a regulator of 1-aminocyclopropane-1-carboxylic acid synthase (Acs2) gene expression. ACC oxidase may play a similar role in signal transduction after post-translational processing. ACC oxidase becomes inactivated by fragmentation and apparently has intrinsic protease and transpeptidase activity. ACC oxidase contains several amino acid sequence motifs for putative protein–protein interactions, phosphokinases and cysteine protease. ACC oxidase is subject to autophosphorylaton in vitro and promotes phosphorylation of some apple fruit proteins in a ripening-dependent manner. PMID:24244837

Conflict-related anterior cingulate functional connectivity is associated with past suicidal ideation and behavior in recent-onset schizophrenia.

PubMed

Minzenberg, Michael J; Lesh, Tyler; Niendam, Tara; Yoon, Jong H; Cheng, Yaoan; Rhoades, Remy; Carter, Cameron S

2015-06-01

Suicide is highly prevalent in schizophrenia (SZ), yet it remains unclear how suicide risk factors such as past suicidal ideation or behavior relate to brain function. Circuits modulated by the prefrontal cortex (PFC) are altered in SZ, including in dorsal anterior cingulate cortex (dACC) during conflict-monitoring (an important component of cognitive control), and dACC changes are observed in post-mortem studies of heterogeneous suicide victims. We tested whether conflict-related dACC functional connectivity is associated with past suicidal ideation and behavior in SZ. 32 patients with recent-onset of DSM-IV-TR-defined SZ were evaluated with the Columbia Suicide Severity Rating Scale and functional MRI during cognitive control (AX-CPT) task performance. Group-level regression models relating past history of suicidal ideation or behavior to dACC-seeded functional connectivity during conflict-monitoring controlled for severity of depression, psychosis and impulsivity. Past suicidal ideation was associated with relatively higher functional connectivity of the dACC with the precuneus during conflict-monitoring. Intensity of worst-point past suicidal ideation was associated with relatively higher dACC functional connectivity in medial parietal lobe and striato-thalamic nuclei. In contrast, among those with past suicidal ideation (n = 17), past suicidal behavior was associated with lower conflict-related dACC connectivity with multiple lateral and medial PFC regions, parietal and temporal cortical regions. This study provides unique evidence that recent-onset schizophrenia patients with past suicidal ideation or behavior show altered dACC-based circuit function during conflict-monitoring. Suicidal ideation and suicidal behavior have divergent patterns of associated dACC functional connectivity, suggesting a differing pattern of conflict-related brain dysfunction with these two distinct features of suicide phenomenology. Published by Elsevier Ltd.

Chronic Suppression of Acetyl-CoA Carboxylase 1 in β-Cells Impairs Insulin Secretion via Inhibition of Glucose Rather Than Lipid Metabolism*

PubMed Central

Ronnebaum, Sarah M.; Joseph, Jamie W.; Ilkayeva, Olga; Burgess, Shawn C.; Lu, Danhong; Becker, Thomas C.; Sherry, A. Dean; Newgard, Christopher B.

2008-01-01

Acetyl-CoA carboxylase 1 (ACC1) currently is being investigated as a target for treatment of obesity-associated dyslipidemia and insulin resistance. To investigate the effects of ACC1 inhibition on insulin secretion, three small interfering RNA (siRNA) duplexes targeting ACC1 (siACC1) were transfected into the INS-1-derived cell line, 832/13; the most efficacious duplex was also cloned into an adenovirus and used to transduce isolated rat islets. Delivery of the siACC1 duplexes decreased ACC1 mRNA by 60–80% in 832/13 cells and islets and enzyme activity by 46% compared with cells treated with a non-targeted siRNA. Delivery of siACC1 decreased glucose-stimulated insulin secretion (GSIS) by 70% in 832/13 cells and by 33% in islets. Surprisingly, siACC1 treatment decreased glucose oxidation by 49%, and the ATP:ADP ratio by 52%, accompanied by clear decreases in pyruvate cycling activity and tricarboxylic acid cycle intermediates. Exposure of siACC1-treated cells to the pyruvate cycling substrate dimethylmalate restored GSIS to normal without recovery of the depressed ATP:ADP ratio. In siACC1-treated cells, glucokinase protein levels were decreased by 25%, which correlated with a 36% decrease in glycogen synthesis and a 33% decrease in glycolytic flux. Furthermore, acute addition of the ACC1 inhibitor 5-(tetradecyloxy)-2-furoic acid (TOFA) to β-cells suppressed [14C]glucose incorporation into lipids but had no effect on GSIS, whereas chronic TOFA administration suppressed GSIS and glucose metabolism. In sum, chronic, but not acute, suppression of ACC1 activity impairs GSIS via inhibition of glucose rather than lipid metabolism. These findings raise concerns about the use of ACC inhibitors for diabetes therapy. PMID:18381287

Chronic suppression of acetyl-CoA carboxylase 1 in beta-cells impairs insulin secretion via inhibition of glucose rather than lipid metabolism.

PubMed

Ronnebaum, Sarah M; Joseph, Jamie W; Ilkayeva, Olga; Burgess, Shawn C; Lu, Danhong; Becker, Thomas C; Sherry, A Dean; Newgard, Christopher B

2008-05-23

Acetyl-CoA carboxylase 1 (ACC1) currently is being investigated as a target for treatment of obesity-associated dyslipidemia and insulin resistance. To investigate the effects of ACC1 inhibition on insulin secretion, three small interfering RNA (siRNA) duplexes targeting ACC1 (siACC1) were transfected into the INS-1-derived cell line, 832/13; the most efficacious duplex was also cloned into an adenovirus and used to transduce isolated rat islets. Delivery of the siACC1 duplexes decreased ACC1 mRNA by 60-80% in 832/13 cells and islets and enzyme activity by 46% compared with cells treated with a non-targeted siRNA. Delivery of siACC1 decreased glucose-stimulated insulin secretion (GSIS) by 70% in 832/13 cells and by 33% in islets. Surprisingly, siACC1 treatment decreased glucose oxidation by 49%, and the ATP:ADP ratio by 52%, accompanied by clear decreases in pyruvate cycling activity and tricarboxylic acid cycle intermediates. Exposure of siACC1-treated cells to the pyruvate cycling substrate dimethylmalate restored GSIS to normal without recovery of the depressed ATP:ADP ratio. In siACC1-treated cells, glucokinase protein levels were decreased by 25%, which correlated with a 36% decrease in glycogen synthesis and a 33% decrease in glycolytic flux. Furthermore, acute addition of the ACC1 inhibitor 5-(tetradecyloxy)-2-furoic acid (TOFA) to beta-cells suppressed [(14)C]glucose incorporation into lipids but had no effect on GSIS, whereas chronic TOFA administration suppressed GSIS and glucose metabolism. In sum, chronic, but not acute, suppression of ACC1 activity impairs GSIS via inhibition of glucose rather than lipid metabolism. These findings raise concerns about the use of ACC inhibitors for diabetes therapy.

Dissociable contributions of anterior cingulate cortex and basolateral amygdala on a rodent cost/benefit decision-making task of cognitive effort.

PubMed

Hosking, Jay G; Cocker, Paul J; Winstanley, Catharine A

2014-06-01

Personal success often requires the choice to expend greater effort for larger rewards, and deficits in such effortful decision making accompany a number of illnesses including depression, schizophrenia, and attention-deficit/hyperactivity disorder. Animal models have implicated brain regions such as the basolateral amygdala (BLA) and anterior cingulate cortex (ACC) in physical effort-based choice, but disentangling the unique contributions of these two regions has proven difficult, and effort demands in industrialized society are predominantly cognitive in nature. Here we utilize the rodent cognitive effort task (rCET), a modification of the five-choice serial reaction-time task, wherein animals can choose to expend greater visuospatial attention to obtain larger sucrose rewards. Temporary inactivation (via baclofen-muscimol) of BLA and ACC showed dissociable effects: BLA inactivation caused hard-working rats to 'slack off' and 'slacker' rats to work harder, whereas ACC inactivation caused all animals to reduce willingness to expend mental effort. Furthermore, BLA inactivation increased the time needed to make choices, whereas ACC inactivation increased motor impulsivity. These data illuminate unique contributions of BLA and ACC to effort-based decision making, and imply overlapping yet distinct circuitry for cognitive vs physical effort. Our understanding of effortful decision making may therefore require expanding our models beyond purely physical costs.

Discordant correlation of breast adenoid cystic carcinoma on imaging and pathology: A case report and literature review on surgical management.

PubMed

Yan, Zhiyan; Leong, May Ying; Lim, Geok Hoon

2018-01-01

Adenoid cystic carcinomas (ACC) of the breast are extremely rare tumours, accounting for <0.1% of newly diagnosed breast cancer cases. Little data exist regarding the correlation of radiological findings with histology of this rare subtype. To our knowledge, gross size discrepancy between the 2 modalities has not been reported. We describe a case of ACC with appreciable size discordance between imaging and pathology report. A 71 years old lady presented with a painless right breast lump of a few months duration. Clinical examination revealed a 1.5 cm right breast upper outer quadrant mass. Axillary and systemic examinations were unremarkable. Mammogram showed an asymmetric density in the right upper outer quadrant which corresponded to a suspicious nodule measuring about 2 cm on the ultrasound. Ultrasound of the axilla showed an indeterminate right lymph node. Core needle biopsy of the right breast nodule showed ACC while the lymph node biopsy was non- metastatic. Staging scans did not reveal any definite distant metastasis. Her naso-endoscopy and MRI of the neck were normal. She underwent a right mastectomy and sentinel lymph node biopsy. Final histology returned as a grade II 55 mm ACC. Lympho-vascular invasion was absent. The tumour was triple negative for Estrogen receptor (ER), Progesterone receptor (PR) and Human epidermal receptor 2 (HER 2). Sentinel lymph node biopsy was negative for metastasis. She recovered well but declined adjuvant chemotherapy and radiation therapy. She is currently well 6 months post operation. ACC is an extremely rare subtype, therefore there are limited reports in literature on its imaging and pathological characteristics. Of this sparse data, there was no mention that there might be a big size discrepancy between the 2 modalities. This appreciable discrepancy has implications for pre-operative planning and the choice of breast surgery. It will be useful if the pathological extent of ACC could be determined more accurately radiologically. However, there are no distinctive imaging characteristics for ACC. ACC can appear as a smooth round mass similar to that of a benign mass or as an irregular mass on mammogram. On ultrasound, ACC often manifested as a hypo- echoic heterogeneous mass with minimal vascularity on Doppler imaging and may have an indistinct margin. MRI has a higher sensitivity than mammogram and ultrasound in determining the true extent of the tumour, but there remains little data on its usefulness in ACC. ACC can be extensively infiltrative and present much larger than its radiological size, as reported in our case. Use of better imaging modalities judiciously, in these cases, are needed to more accurately predict the true pathological size of ACC to prevent inadequate surgery. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Biomineralisation by earthworms - an investigation into the stability and distribution of amorphous calcium carbonate.

PubMed

Hodson, Mark E; Benning, Liane G; Demarchi, Bea; Penkman, Kirsty E H; Rodriguez-Blanco, Juan D; Schofield, Paul F; Versteegh, Emma A A

Many biominerals form from amorphous calcium carbonate (ACC), but this phase is highly unstable when synthesised in its pure form inorganically. Several species of earthworm secrete calcium carbonate granules which contain highly stable ACC. We analysed the milky fluid from which granules form and solid granules for amino acid (by liquid chromatography) and functional group (by Fourier transform infrared (FTIR) spectroscopy) compositions. Granule elemental composition was determined using inductively coupled plasma-optical emission spectroscopy (ICP-OES) and electron microprobe analysis (EMPA). Mass of ACC present in solid granules was quantified using FTIR and compared to granule elemental and amino acid compositions. Bulk analysis of granules was of powdered bulk material. Spatially resolved analysis was of thin sections of granules using synchrotron-based μ-FTIR and EMPA electron microprobe analysis. The milky fluid from which granules form is amino acid-rich (≤ 136 ± 3 nmol mg -1 (n = 3; ± std dev) per individual amino acid); the CaCO 3 phase present is ACC. Even four years after production, granules contain ACC. No correlation exists between mass of ACC present and granule elemental composition. Granule amino acid concentrations correlate well with ACC content (r ≥ 0.7, p ≤ 0.05) consistent with a role for amino acids (or the proteins they make up) in ACC stabilisation. Intra-granule variation in ACC (RSD = 16%) and amino acid concentration (RSD = 22-35%) was high for granules produced by the same earthworm. Maps of ACC distribution produced using synchrotron-based μ-FTIR mapping of granule thin sections and the relative intensity of the ν 2 : ν 4 peak ratio, cluster analysis and component regression using ACC and calcite standards showed similar spatial distributions of likely ACC-rich and calcite-rich areas. We could not identify organic peaks in the μ-FTIR spectra and thus could not determine whether ACC-rich domains also had relatively high amino acid concentrations. No correlation exists between ACC distribution and elemental concentrations determined by EMPA. ACC present in earthworm CaCO 3 granules is highly stable. Our results suggest a role for amino acids (or proteins) in this stability. We see no evidence for stabilisation of ACC by incorporation of inorganic components. Graphical abstractSynchrotron-based μ-FTIR mapping was used to determine the spatial distribution of amorphous calcium carbonate in earthworm-produced CaCO 3 granules.

24 CFR 990.150 - Limited vacancies.

Code of Federal Regulations, 2011 CFR

2011-04-01

... shall pay operating subsidy for a limited number of vacant units under an ACC if the annualized vacancy... percent of the unit months under an ACC) for the period July 1, 2004, to June 30, 2005, and (2) Three... to five vacant units not to exceed 100 percent of the unit months under an ACC. For example, a PHA...

24 CFR 990.150 - Limited vacancies.

Code of Federal Regulations, 2010 CFR

2010-04-01

... shall pay operating subsidy for a limited number of vacant units under an ACC if the annualized vacancy... percent of the unit months under an ACC) for the period July 1, 2004, to June 30, 2005, and (2) Three... to five vacant units not to exceed 100 percent of the unit months under an ACC. For example, a PHA...

Biomineral shell formation under ocean acidification: a shift from order to chaos.

PubMed

Fitzer, Susan C; Chung, Peter; Maccherozzi, Francesco; Dhesi, Sarnjeet S; Kamenos, Nicholas A; Phoenix, Vernon R; Cusack, Maggie

2016-02-15

Biomineral production in marine organisms employs transient phases of amorphous calcium carbonate (ACC) in the construction of crystalline shells. Increasing seawater pCO2 leads to ocean acidification (OA) with a reduction in oceanic carbonate concentration which could have a negative impact on shell formation and therefore survival. We demonstrate significant changes in the hydrated and dehydrated forms of ACC in the aragonite and calcite layers of Mytilus edulis shells cultured under acidification conditions (1000 μatm pCO2) compared to present day conditions (380 μatm pCO2). In OA conditions, Mytilus edulis has more ACC at crystalisation sites. Here, we use the high-spatial resolution of synchrotron X-ray Photo Emission Electron Microscopy (XPEEM) combined with X-ray Absorption Spectroscopy (XAS) to investigate the influence of OA on the ACC formation in the shells of adult Mytilus edulis. Electron Backscatter Diffraction (EBSD) confirms that OA reduces crystallographic control of shell formation. The results demonstrate that OA induces more ACC formation and less crystallographic control in mussels suggesting that ACC is used as a repair mechanism to combat shell damage under OA. However, the resultant reduced crystallographic control in mussels raises concerns for shell protective function under predation and changing environments.

Biomineral shell formation under ocean acidification: a shift from order to chaos

PubMed Central

Fitzer, Susan C.; Chung, Peter; Maccherozzi, Francesco; Dhesi, Sarnjeet S.; Kamenos, Nicholas A.; Phoenix, Vernon R.; Cusack, Maggie

2016-01-01

Biomineral production in marine organisms employs transient phases of amorphous calcium carbonate (ACC) in the construction of crystalline shells. Increasing seawater pCO2 leads to ocean acidification (OA) with a reduction in oceanic carbonate concentration which could have a negative impact on shell formation and therefore survival. We demonstrate significant changes in the hydrated and dehydrated forms of ACC in the aragonite and calcite layers of Mytilus edulis shells cultured under acidification conditions (1000 μatm pCO2) compared to present day conditions (380 μatm pCO2). In OA conditions, Mytilus edulis has more ACC at crystalisation sites. Here, we use the high-spatial resolution of synchrotron X-ray Photo Emission Electron Microscopy (XPEEM) combined with X-ray Absorption Spectroscopy (XAS) to investigate the influence of OA on the ACC formation in the shells of adult Mytilus edulis. Electron Backscatter Diffraction (EBSD) confirms that OA reduces crystallographic control of shell formation. The results demonstrate that OA induces more ACC formation and less crystallographic control in mussels suggesting that ACC is used as a repair mechanism to combat shell damage under OA. However, the resultant reduced crystallographic control in mussels raises concerns for shell protective function under predation and changing environments. PMID:26876022

Biomineral shell formation under ocean acidification: a shift from order to chaos

NASA Astrophysics Data System (ADS)

Fitzer, Susan C.; Chung, Peter; Maccherozzi, Francesco; Dhesi, Sarnjeet S.; Kamenos, Nicholas A.; Phoenix, Vernon R.; Cusack, Maggie

2016-02-01

Biomineral production in marine organisms employs transient phases of amorphous calcium carbonate (ACC) in the construction of crystalline shells. Increasing seawater pCO2 leads to ocean acidification (OA) with a reduction in oceanic carbonate concentration which could have a negative impact on shell formation and therefore survival. We demonstrate significant changes in the hydrated and dehydrated forms of ACC in the aragonite and calcite layers of Mytilus edulis shells cultured under acidification conditions (1000 μatm pCO2) compared to present day conditions (380 μatm pCO2). In OA conditions, Mytilus edulis has more ACC at crystalisation sites. Here, we use the high-spatial resolution of synchrotron X-ray Photo Emission Electron Microscopy (XPEEM) combined with X-ray Absorption Spectroscopy (XAS) to investigate the influence of OA on the ACC formation in the shells of adult Mytilus edulis. Electron Backscatter Diffraction (EBSD) confirms that OA reduces crystallographic control of shell formation. The results demonstrate that OA induces more ACC formation and less crystallographic control in mussels suggesting that ACC is used as a repair mechanism to combat shell damage under OA. However, the resultant reduced crystallographic control in mussels raises concerns for shell protective function under predation and changing environments.

Report of the Annual Scientific Session of the American College of Cardiology (ACC) 2018, Orlando.

PubMed

Hashimoto, Takuya; Ako, Junya

2018-04-28

The 67 th Annual Scientific Session and Expo of the American College of Cardiology (ACC) were held at the Orange County Convention Center, Orlando, from March 10-12, 2018. This meeting offered 2,700 accepted abstracts presented in oral and poster sessions by 2,100 experts and 37 Late-Breaking Clinical Trials and Featured Clinical Research presentations. This report introduces the key presentations and highlights from the ACC 2018 Scientific Session.

Down-regulation of NR2B receptors partially contributes to analgesic effects of Gentiopicroside in persistent inflammatory pain.

PubMed

Chen, Lei; Liu, Jin-cheng; Zhang, Xiao-nan; Guo, Yan-yan; Xu, Zhao-hui; Cao, Wei; Sun, Xiao-li; Sun, Wen-ji; Zhao, Ming-Gao

2008-06-01

Gentiopicroside is one of the secoiridoid compound isolated from Gentiana lutea. It exhibits analgesic activities in the mice. The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission and induce glutamate NMDA NR2B receptor expression in the ACC. But little is known about Gentiopicroside on the persistent inflammatory pain and chronic pain-induced synaptic transmission changes in the ACC. The present study was undertaken to investigate its analgesic activities and central synaptic modulation to the peripheral painful inflammation. Gentiopicroside produced significant analgesic effects against persistent inflammatory pain stimuli in mice. Systemic administration of Gentiopicroside significantly reversed NR2B over-expression during the chronic phases of persistent inflammation caused by hind-paw administration of complete Freunds adjuvant (CFA) in mice. Whole-cell patch clamp recordings revealed that Gentiopicroside significantly reduced NR2B receptors mediated postsynaptic currents in the ACC. Our findings provide strong evidence that analgesic effects of Gentiopicroside involve down-regulation of NR2B receptors in the ACC to persistent inflammatory pain.

Roles and Responsibilities--Single College Orientation.

ERIC Educational Resources Information Center

Fonte, Richard

Austin Community College (ACC) is undergoing reorganization in an attempt to create a "single college" organizational structure to replace its current "campus with five competing colleges" model. By doing so, ACC hopes to create an atmosphere in which short and long range planning efforts are aimed at the overall good of the…

Graphics Processing Unit Acceleration of Gyrokinetic Turbulence Simulations

NASA Astrophysics Data System (ADS)

Hause, Benjamin; Parker, Scott; Chen, Yang

2013-10-01

We find a substantial increase in on-node performance using Graphics Processing Unit (GPU) acceleration in gyrokinetic delta-f particle-in-cell simulation. Optimization is performed on a two-dimensional slab gyrokinetic particle simulation using the Portland Group Fortran compiler with the OpenACC compiler directives and Fortran CUDA. Mixed implementation of both Open-ACC and CUDA is demonstrated. CUDA is required for optimizing the particle deposition algorithm. We have implemented the GPU acceleration on a third generation Core I7 gaming PC with two NVIDIA GTX 680 GPUs. We find comparable, or better, acceleration relative to the NERSC DIRAC cluster with the NVIDIA Tesla C2050 computing processor. The Tesla C 2050 is about 2.6 times more expensive than the GTX 580 gaming GPU. We also see enormous speedups (10 or more) on the Titan supercomputer at Oak Ridge with Kepler K20 GPUs. Results show speed-ups comparable or better than that of OpenMP models utilizing multiple cores. The use of hybrid OpenACC, CUDA Fortran, and MPI models across many nodes will also be discussed. Optimization strategies will be presented. We will discuss progress on optimizing the comprehensive three dimensional general geometry GEM code.

Acetyl-CoA carboxylase rewires cancer metabolism to allow cancer cells to survive inhibition of the Warburg effect by cetuximab.

PubMed

Luo, Jingtao; Hong, Yun; Lu, Yang; Qiu, Songbo; Chaganty, Bharat K R; Zhang, Lun; Wang, Xudong; Li, Qiang; Fan, Zhen

2017-01-01

Cetuximab inhibits HIF-1-regulated glycolysis in cancer cells, thereby reversing the Warburg effect and leading to inhibition of cancer cell metabolism. AMP-activated protein kinase (AMPK) is activated after cetuximab treatment, and a sustained AMPK activity is a mechanism contributing to cetuximab resistance. Here, we investigated how acetyl-CoA carboxylase (ACC), a downstream target of AMPK, rewires cancer metabolism in response to cetuximab treatment. We found that introduction of experimental ACC mutants lacking the AMPK phosphorylation sites (ACC1_S79A and ACC2_S212A) into head and neck squamous cell carcinoma (HNSCC) cells protected HNSCC cells from cetuximab-induced growth inhibition. HNSCC cells with acquired cetuximab resistance contained not only high levels of T172-phosphorylated AMPK and S79-phosphorylated ACC1 but also an increased level of total ACC. These findings were corroborated in tumor specimens of HNSCC patients treated with cetuximab. Cetuximab plus TOFA (an allosteric inhibitor of ACC) achieved remarkable growth inhibition of cetuximab-resistant HNSCC xenografts. Our data suggest a novel paradigm in which cetuximab-mediated activation of AMPK and subsequent phosphorylation and inhibition of ACC is followed by a compensatory increase in total ACC, which rewires cancer metabolism from glycolysis-dependent to lipogenesis-dependent. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Agreement between activity-monitoring devices during home rehabilitation: a substudy of the AAA STOP trial.

PubMed

Myers, Jonathan; Dupain, Mandi; Vu, Andrew; Jaffe, Alyssa; Smith, Kimberly; Fonda, Holly; Dalman, Ronald

2014-01-01

As part of a home-based rehabilitation program, 24 older adult patients (71 ± 3 years) with abdominal aortic aneurysm (AAA) disease underwent 3 days (12 awake hr/day) of activity monitoring using an accelerometer (ACC), a pedometer, and a heart rate (HR) monitor, and recorded hourly activity logs. Subjects then underwent an interview to complete a 3-day activity recall questionnaire (3-DR). Mean energy expenditure (EE) in kcals/ day for HR, ACC, and 3-DR were 1,687 ± 458, 2,068 ± 529, and 1,974 ± 491, respectively. Differences in EE were not significant between 3-DR and ACC, but HR differed from both ACC (p < .001) and 3-DR (p < .01). ACC and 3-DR had the highest agreement, with a coefficient of variation of 7.9% and r = .86. Thus, ACC provided a reasonably accurate reflection of EE based the criterion measure, an activity recall questionnaire. ACC can be effectively used to monitor EE to achieve an appropriate training stimulus during home-based cardiac rehabilitation.

Molecular cloning, expression, and stress response of the estrogen-related receptor gene (AccERR) from Apis cerana cerana

NASA Astrophysics Data System (ADS)

Zhang, Weixing; Zhu, Ming; Zhang, Ge; Liu, Feng; Wang, Hongfang; Guo, Xingqi; Xu, Baohua

2016-04-01

Estrogen-related receptor (ERR), which belongs to the nuclear receptor superfamily, has been implicated in diverse physiological processes involving the estrogen signaling pathway. However, little information is available on ERR in Apis cerana cerana. In this report, we isolated the ERR gene and investigated its involvement in antioxidant defense. Quantitative real-time polymerase chain reaction (qPCR) revealed that the highest mRNA expression occurred in eggs during different developmental stages. The expression levels of AccERR were highest in the muscle, followed by the rectum. The predicted transcription factor binding sites in the promoter of AccERR suggested that AccERR potentially functions in early development and in environmental stress responses. The expression of AccERR was induced by cold (4 °C), heat (42 °C), ultraviolet light (UV), HgCl2, and various types of pesticides (phoxim, deltamethrin, triadimefon, and cyhalothrin). Western blot was used to measure the expression levels of AccERR protein. These data suggested that AccERR might play a vital role in abiotic stress responses.

Alleviating neuropathic pain mechanical allodynia by increasing Cdh1 in the anterior cingulate cortex.

PubMed

Tan, Wei; Yao, Wen-Long; Hu, Rong; Lv, You-You; Wan, Li; Zhang, Chuan-Han; Zhu, Chang

2015-09-12

Plastic changes in the anterior cingulate cortex (ACC) are critical in the pathogenesis of pain hypersensitivity caused by injury to peripheral nerves. Cdh1, a co-activator subunit of anaphase-promoting complex/cyclosome (APC/C) regulates synaptic differentiation and transmission. Based on this, we hypothesised that the APC/C-Cdh1 played an important role in long-term plastic changes induced by neuropathic pain in ACC. We employed spared nerve injury (SNI) model in rat and found Cdh1 protein level in the ACC was down-regulated 3, 7 and 14 days after SNI surgery. We detected increase in c-Fos expression, numerical increase of organelles, swollen myelinated fibre and axon collapse of neuronal cells in the ACC of SNI rat. Additionally, AMPA receptor GluR1 subunit protein level was up-regulated on the membrane through a pathway that involves EphA4 mediated by APC/C-Cdh1, 3 and 7 days after SNI surgery. To confirm the effect of Cdh1 in neuropathic pain, Cdh1-expressing lentivirus was injected into the ACC of SNI rat. Intra-ACC treatment with Cdh1-expressing lentivirus vectors elevated Cdh1 levels, erased synaptic strengthening, as well as alleviating established mechanical allodynia in SNI rats. We also found Cdh1-expressing lentivirus normalised SNI-induced redistribution of AMPA receptor GluR1 subunit in ACC by regulating AMPA receptor trafficking. These results provide evidence that Cdh1 in ACC synapses may offer a novel therapeutic strategy for treating chronic neuropathic pain.

Clinical and molecular insights into adenoid cystic carcinoma: Neural crest‐like stemness as a target

PubMed Central

Panaccione, Alexander; Chang, Michael T.; Ivanov, Sergey V.

2016-01-01

Objectives This review surveys trialed therapies and molecular defects in adenoid cystic carcinoma (ACC), with an emphasis on neural crest‐like stemness characteristics of newly discovered cancer stem cells (CSCs) and therapies that may target these CSCs. Data Sources Articles available on Pubmed or OVID MEDLINE databases and unpublished data. Review Methods Systematic review of articles pertaining to ACC and neural crest‐like stem cells. Results Adenoid cystic carcinoma of the salivary gland is a slowly growing but relentless cancer that is prone to nerve invasion and metastases. A lack of understanding of molecular etiology and absence of targetable drivers has limited therapy for patients with ACC to surgery and radiation. Currently, no curative treatments are available for patients with metastatic disease, which highlights the need for effective new therapies. Research in this area has been inhibited by the lack of validated cell lines and a paucity of clinically useful markers. The ACC research environment has recently improved, thanks to the introduction of novel tools, technologies, approaches, and models. Improved understanding of ACC suggests that neural crest‐like stemness is a major target in this rare tumor. New cell culture techniques and patient‐derived xenografts provide tools for preclinical testing. Conclusion Preclinical research has not identified effective targets in ACC, as confirmed by the large number of failed clinical trials. New molecular data suggest that drivers of neural crest‐like stemness may be required for maintenance of ACC; as such, CSCs are a target for therapy of ACC. PMID:28894804

High intensity interval training improves liver and adipose tissue insulin sensitivity.

PubMed

Marcinko, Katarina; Sikkema, Sarah R; Samaan, M Constantine; Kemp, Bruce E; Fullerton, Morgan D; Steinberg, Gregory R

2015-12-01

Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine-alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC.

24 CFR 943.115 - What programs are covered under this subpart?

Code of Federal Regulations, 2011 CFR

2011-04-01

... Annual Contributions Contract (ACC) with HUD; and (2) PHA administration of grants to the PHA in... to an ACC entered under the Request for Proposals (RFP) published May 19, 1999 (64 FR 27358); (2...

24 CFR 943.115 - What programs are covered under this subpart?

Code of Federal Regulations, 2010 CFR

2010-04-01

... Annual Contributions Contract (ACC) with HUD; and (2) PHA administration of grants to the PHA in... to an ACC entered under the Request for Proposals (RFP) published May 19, 1999 (64 FR 27358); (2...

Musicians Are Better than Non-musicians in Frequency Change Detection: Behavioral and Electrophysiological Evidence

PubMed Central

Liang, Chun; Earl, Brian; Thompson, Ivy; Whitaker, Kayla; Cahn, Steven; Xiang, Jing; Fu, Qian-Jie; Zhang, Fawen

2016-01-01

Objective: The objectives of this study were: (1) to determine if musicians have a better ability to detect frequency changes under quiet and noisy conditions; (2) to use the acoustic change complex (ACC), a type of electroencephalographic (EEG) response, to understand the neural substrates of musician vs. non-musician difference in frequency change detection abilities. Methods: Twenty-four young normal hearing listeners (12 musicians and 12 non-musicians) participated. All participants underwent psychoacoustic frequency detection tests with three types of stimuli: tones (base frequency at 160 Hz) containing frequency changes (Stim 1), tones containing frequency changes masked by low-level noise (Stim 2), and tones containing frequency changes masked by high-level noise (Stim 3). The EEG data were recorded using tones (base frequency at 160 and 1200 Hz, respectively) containing different magnitudes of frequency changes (0, 5, and 50% changes, respectively). The late-latency evoked potential evoked by the onset of the tones (onset LAEP or N1-P2 complex) and that evoked by the frequency change contained in the tone (the acoustic change complex or ACC or N1′-P2′ complex) were analyzed. Results: Musicians significantly outperformed non-musicians in all stimulus conditions. The ACC and onset LAEP showed similarities and differences. Increasing the magnitude of frequency change resulted in increased ACC amplitudes. ACC measures were found to be significantly different between musicians (larger P2′ amplitude) and non-musicians for the base frequency of 160 Hz but not 1200 Hz. Although the peak amplitude in the onset LAEP appeared to be larger and latency shorter in musicians than in non-musicians, the difference did not reach statistical significance. The amplitude of the onset LAEP is significantly correlated with that of the ACC for the base frequency of 160 Hz. Conclusion: The present study demonstrated that musicians do perform better than non-musicians in detecting frequency changes in quiet and noisy conditions. The ACC and onset LAEP may involve different but overlapping neural mechanisms. Significance: This is the first study using the ACC to examine music-training effects. The ACC measures provide an objective tool for documenting musical training effects on frequency detection. PMID:27826221

Human-Automation Interaction Design for Adaptive Cruise Control Systems of Ground Vehicles.

PubMed

Eom, Hwisoo; Lee, Sang Hun

2015-06-12

A majority of recently developed advanced vehicles have been equipped with various automated driver assistance systems, such as adaptive cruise control (ACC) and lane keeping assistance systems. ACC systems have several operational modes, and drivers can be unaware of the mode in which they are operating. Because mode confusion is a significant human error factor that contributes to traffic accidents, it is necessary to develop user interfaces for ACC systems that can reduce mode confusion. To meet this requirement, this paper presents a new human-automation interaction design methodology in which the compatibility of the machine and interface models is determined using the proposed criteria, and if the models are incompatible, one or both of the models is/are modified to make them compatible. To investigate the effectiveness of our methodology, we designed two new interfaces by separately modifying the machine model and the interface model and then performed driver-in-the-loop experiments. The results showed that modifying the machine model provides a more compact, acceptable, effective, and safe interface than modifying the interface model.

Human-Automation Interaction Design for Adaptive Cruise Control Systems of Ground Vehicles

PubMed Central

Eom, Hwisoo; Lee, Sang Hun

2015-01-01

A majority of recently developed advanced vehicles have been equipped with various automated driver assistance systems, such as adaptive cruise control (ACC) and lane keeping assistance systems. ACC systems have several operational modes, and drivers can be unaware of the mode in which they are operating. Because mode confusion is a significant human error factor that contributes to traffic accidents, it is necessary to develop user interfaces for ACC systems that can reduce mode confusion. To meet this requirement, this paper presents a new human-automation interaction design methodology in which the compatibility of the machine and interface models is determined using the proposed criteria, and if the models are incompatible, one or both of the models is/are modified to make them compatible. To investigate the effectiveness of our methodology, we designed two new interfaces by separately modifying the machine model and the interface model and then performed driver-in-the-loop experiments. The results showed that modifying the machine model provides a more compact, acceptable, effective, and safe interface than modifying the interface model. PMID:26076406

Acetyl-CoA carboxylase in Reuber hepatoma cells: variation in enzyme activity, insulin regulation, and cellular lipid content.

PubMed

Bianchi, A; Evans, J L; Nordlund, A C; Watts, T D; Witters, L A

1992-01-01

Reuber hepatoma cells are useful cultured lines for the study of insulin action, lipid and lipoprotein metabolism, and the regulation of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid biosynthesis. During investigations in different clonal lines of these cells, we have uncovered marked intercellular variability in the activity, enzyme content, and insulin regulation of ACC paralleled by differences in cellular neutral lipid (triglyceride) content. Two contrasting clonal lines, Fao and H356A-1, have been studied in detail. Several features distinguish these two lines, including differences in ACC activity and enzyme kinetics, the content of the two major hepatic ACC isozymes (Mr 280,000 and 265,000 Da) and their heteroisozymic complex, the extent of ACC phosphorylation, and the ability of ACC to be activated on stimulation by insulin and insulinomimetic agonists. As studied by Nile Red staining and fluorescence-activated cell sorting, these two lines also display marked differences in neutral lipid content, which correlates with both basal levels of ACC activity and inhibition of ACC by the fatty acid analog, 5-(tetradecyloxy)-2-furoic acid (TOFA). These results emphasize the importance of characterization of any particular clonal line of Reuber cells for studies of enzyme regulation, substrate metabolism, and hormone action. With respect to ACC, studies in contrasting clonal lines of Reuber cells could provide valuable clues to understanding both the complex mechanisms of intracellular ACC regulation in the absence and presence of hormones and its regulatory role(s) in overall hepatic lipid metabolism.

Advanced MR Imaging of the Human Nucleus Accumbens--Additional Guiding Tool for Deep Brain Stimulation.

PubMed

Lucas-Neto, Lia; Reimão, Sofia; Oliveira, Edson; Rainha-Campos, Alexandre; Sousa, João; Nunes, Rita G; Gonçalves-Ferreira, António; Campos, Jorge G

2015-07-01

The human nucleus accumbens (Acc) has become a target for deep brain stimulation (DBS) in some neuropsychiatric disorders. Nonetheless, even with the most recent advances in neuroimaging it remains difficult to accurately delineate the Acc and closely related subcortical structures, by conventional MRI sequences. It is our purpose to perform a MRI study of the human Acc and to determine whether there are reliable anatomical landmarks that enable the precise location and identification of the nucleus and its core/shell division. For the Acc identification and delineation, based on anatomical landmarks, T1WI, T1IR and STIR 3T-MR images were acquired in 10 healthy volunteers. Additionally, 32-direction DTI was obtained for Acc segmentation. Seed masks for the Acc were generated with FreeSurfer and probabilistic tractography was performed using FSL. The probability of connectivity between the seed voxels and distinct brain areas was determined and subjected to k-means clustering analysis, defining 2 different regions. With conventional T1WI, the Acc borders are better defined through its surrounding anatomical structures. The DTI color-coded vector maps and IR sequences add further detail in the Acc identification and delineation. Additionally, using probabilistic tractography it is possible to segment the Acc into a core and shell division and establish its structural connectivity with different brain areas. Advanced MRI techniques allow in vivo delineation and segmentation of the human Acc and represent an additional guiding tool in the precise and safe target definition for DBS. © 2015 International Neuromodulation Society.

Transformation and crystallization energetics of synthetic and biogenic amorphous calcium carbonate

PubMed Central

Radha, A. V.; Forbes, Tori Z.; Killian, Christopher E.; Gilbert, P. U. P. A.; Navrotsky, Alexandra

2010-01-01

Amorphous calcium carbonate (ACC) is a metastable phase often observed during low temperature inorganic synthesis and biomineralization. ACC transforms with aging or heating into a less hydrated form, and with time crystallizes to calcite or aragonite. The energetics of transformation and crystallization of synthetic and biogenic (extracted from California purple sea urchin larval spicules, Strongylocentrotus purpuratus) ACC were studied using isothermal acid solution calorimetry and differential scanning calorimetry. Transformation and crystallization of ACC can follow an energetically downhill sequence: more metastable hydrated ACC → less metastable hydrated ACC⇒anhydrous ACC ∼ biogenic anhydrous ACC⇒vaterite → aragonite → calcite. In a given reaction sequence, not all these phases need to occur. The transformations involve a series of ordering, dehydration, and crystallization processes, each lowering the enthalpy (and free energy) of the system, with crystallization of the dehydrated amorphous material lowering the enthalpy the most. ACC is much more metastable with respect to calcite than the crystalline polymorphs vaterite or aragonite. The anhydrous ACC is less metastable than the hydrated, implying that the structural reorganization during dehydration is exothermic and irreversible. Dehydrated synthetic and anhydrous biogenic ACC are similar in enthalpy. The transformation sequence observed in biomineralization could be mainly energetically driven; the first phase deposited is hydrated ACC, which then converts to anhydrous ACC, and finally crystallizes to calcite. The initial formation of ACC may be a first step in the precipitation of calcite under a wide variety of conditions, including geological CO2 sequestration. PMID:20810918

Acute Radiation Hypotension in the Rabbit: a Model for the Human Radiation Shock Syndrome.

NASA Astrophysics Data System (ADS)

Makale, Milan Theodore

This study has shown that total body irradiation (TBI) of immature (40 to 100 day old) rabbits leads to an acute fall in mean arterial pressure (MAP) 30 to 90 minutes after exposure, which takes no more than about three minutes, and often results in pressures which are less than 50% of the lowest pre-exposure MAP. This is termed acute cardiovascular collapse (ACC). ACC is often accompanied by ECG T-wave elevation, a sharp rise in ear temperature, labored breathing, pupillary constriction, bladder emptying, and loss of abdominal muscle tone. About 73% of 40 to 100 day rabbits exhibit ACC; the others and most older rabbits display gradual pressure reductions (deliberate hypotension) which may be profound, and which may be accompanied by the same changes associated with ACC. ACC and deliberate hypotension occurred in rabbits cannulated in the dorsal aorta, and in non-operated animals. The decline in MAP for all 40 to 100 day cannulated rabbits (deliberate and ACC responders) is 55.4%. The experiments described below only involved 40 to 100 day cannulated TBI rabbits. Heart region irradiation resulted in an average MAP decline of 29.1%, with 1/15 rabbits showing ACC. Heart shielding during TBI reduced the decline in MAP to 19%, with 1/10 rabbits experiencing ACC. These results imply that the heart region, which includes the heart, part of the lungs, neural receptors, roots of the systemic vessels, and the blood, is a sensitive target. Bilateral vagotomy reduced the decline in MAP to 24.9%, and abolished ACC. Atropine (6 mg/kg) reduced the frequency of ACC to 26%, and the decline in MAP to 41.4%. In 11/13 rabbits the voltage generated by left vagal transmission rose after TBI. The vagi appear to participate in radiation hypotension. Heart shielding together with bilateral vagotomy reduced the decline in MAP to only 9.9%, with no ACC responders. The mean right ventricular pressure (MRVP) rose after TBI in 8/10 rabbits. In animals which displayed either ACC or steep deliberate hypotension, the MRVP rose sharply prior to the rapid decline in MAP. This suggests that the pulmonary blood flow was impeded, possibly causing right heart failure (cor pulmonale), and consequent cardiovascular collapse.

Attenuation of pCREB and Egr1 expression in the insular and anterior cingulate cortices associated with enhancement of CFA-evoked mechanical hypersensitivity after repeated forced swim stress.

PubMed

Imbe, Hiroki; Kimura, Akihisa

2017-09-01

The perception and response to pain are severely impacted by exposure to stressors. In some animal models, stress increases pain sensitivity, which is termed stress-induced hyperalgesia (SIH). The insular cortex (IC) and anterior cingulate cortex (ACC), which are typically activated by noxious stimuli, affect pain perception through the descending pain modulatory system. In the present study, we examined the expression of phospho-cAMP response element-binding protein (pCREB) and early growth response 1 (Egr1) in the IC and ACC at 3h (the acute phase of peripheral tissue inflammation) after complete Freund's adjuvant (CFA) injection in naïve rats and rats preconditioned with forced swim stress (FS) to clarify the effect of FS, a stressor, on cortical cell activities in the rats showing SIH induced by FS. The CFA injection into the hindpaw induced mechanical hypersensitivity and increased the expression of the pCREB and Egr1 in the IC and ACC at 3h after the injection. FS (day 1, 10min; days 2-3, 20min) prior to the CFA injection enhanced the CFA-induced mechanical hypersensitivity and attenuated the increase in the expression of pCREB and Egr1 in the IC and ACC. These findings suggested that FS modulates the CFA injection-induced neuroplasticity in the IC and ACC to enhance the mechanical hypersensitivity. These findings are thought to signify stressor-induced dysfunction of the descending pain modulatory system. Copyright © 2017 Elsevier Inc. All rights reserved.

Adjuvant radiation therapy and survival for adenoid cystic carcinoma of the breast.

PubMed

Sun, Jia-Yuan; Wu, San-Gang; Chen, Shan-Yu; Li, Feng-Yan; Lin, Huan-Xin; Chen, Yong-Xiong; He, Zhen-Yu

2017-02-01

The assess the clinical value of different types of surgical procedures and further analyze the effect of adjuvant radiation therapy (RT) for adenoid cystic carcinoma (ACC) of the breast. Patients with ACC of the breast were identified using a population-based national registration database (Surveillance, Epidemiology, and End Results, SEER). The Kaplan-Meier method and Cox regression models were performed to determine the impact of the surgical procedures and adjuvant RT associated with cause-specific survival (CSS) and overall survival (OS). A total of 478 patients with ACC of the breast were identified. The median follow-up was 59 months. The 10-year CSS and OS were 87.5% and 75.3%, respectively. For the Kaplan-Meier analysis, the 5-year CSS were 96.1%, 91.8%, 90.2%, and 94.1% in patients that received lumpectomy + adjuvant RT, lumpectomy alone, mastectomy alone, and mastectomy + adjuvant RT, respectively (p = 0.026). In the multivariate Cox analyses, lumpectomy + adjuvant RT was an independent prognostic factor for CSS and OS. Patients that received lumpectomy + adjuvant RT had better survival rates than patients that underwent lumpectomy only (CSS, p = 0.018; OS, p = 0.031) and mastectomy only (CSS, p = 0.010; OS, p = 0.004). ACC of the breast has an excellent prognosis. Breast-conserving surgery is a reasonable alternative for patients with ACC of the breast, and adjuvant RT after lumpectomy improved survival rates. Copyright © 2016 Elsevier Ltd. All rights reserved.

In-depth characterization of the salivary adenoid cystic carcinoma transcriptome with emphasis on dominant cell type.

PubMed

Bell, Diana; Bell, Achim H; Bondaruk, Jolanta; Hanna, Ehab Y; Weber, Randall S

2016-05-15

Adenoid cystic carcinoma (ACC), 1 of the most common salivary gland malignancies, arises from the intercalated ducts, which are composed of inner ductal epithelial cells and outer myoepithelial cells. The objective of this study was to determine the genomic subtypes of ACC with emphasis on dominant cell type to identify potential specific biomarkers for each subtype and to improve the understanding of this disease. A whole-genome expression study was performed based on 42 primary salivary ACCs and 5 normal salivary glands. RNA from these specimens was subjected to expression profiling with RNA sequencing, and results were analyzed to identify transcripts in epithelial-dominant ACC (E-ACC), myoepithelial-dominant ACC (M-ACC), and all ACC that were expressed differentially compared with the transcripts in normal salivary tissue. In total, the authors identified 430 differentially expressed transcripts that were unique to E-ACC, 392 that were unique to M-ACC, and 424 that were common to both M-ACC and E-ACC. The sets of E-ACC-specific and M-ACC-specific transcripts were sufficiently large to define and differentiate E-ACC from M-ACC. Ingenuity pathway analysis identified known cancer-related genes for 60% of the E-ACC transcripts, 69% of the M-ACC transcripts, and 68% of the transcripts that were common in both E-ACC and M-ACC. Three sets of highly expressed candidate genes-distal-less homeobox 6 (DLX6) for E-ACC; protein keratin 16 (KRT16), SRY box 11 (SOX11), and v-myb avian myeloblastosis viral oncogene homolog (MYB) for M-ACC; and engrailed 1 (EN1) and statherin (STATH), which are common to both E-ACC and M-ACC)-were further validated at the protein level. The current results enabled the authors to identify novel potential therapeutic targets and biomarkers in E-ACC and M-ACC individually, with the implication that EN1, DLX6, and OTX1 (orthodenticle homeobox 1) are potential drivers of these cancers. Cancer 2016;122:1513-22. © 2016 American Cancer Society. © 2016 American Cancer Society.

24 CFR 884.120 - Responsibility for contract administration and defaults (private-owner/PHA projects).

Code of Federal Regulations, 2010 CFR

2010-04-01

... the Contract, subject to review and audit by HUD. (b) Defaults by PHA and/or owner. (1) The ACC and... assure that the obligations of the PHA to the Owner are carried out. (2) The ACC shall contain a... accordance with the terms of the ACC and the Contract. (3) The Contract shall contain a provision to the...

24 CFR 884.120 - Responsibility for contract administration and defaults (private-owner/PHA projects).

Code of Federal Regulations, 2011 CFR

2011-04-01

... the Contract, subject to review and audit by HUD. (b) Defaults by PHA and/or owner. (1) The ACC and... assure that the obligations of the PHA to the Owner are carried out. (2) The ACC shall contain a... accordance with the terms of the ACC and the Contract. (3) The Contract shall contain a provision to the...

Dissociating response conflict and error likelihood in anterior cingulate cortex.

PubMed

Yeung, Nick; Nieuwenhuis, Sander

2009-11-18

Neuroimaging studies consistently report activity in anterior cingulate cortex (ACC) in conditions of high cognitive demand, leading to the view that ACC plays a crucial role in the control of cognitive processes. According to one prominent theory, the sensitivity of ACC to task difficulty reflects its role in monitoring for the occurrence of competition, or "conflict," between responses to signal the need for increased cognitive control. However, a contrasting theory proposes that ACC is the recipient rather than source of monitoring signals, and that ACC activity observed in relation to task demand reflects the role of this region in learning about the likelihood of errors. Response conflict and error likelihood are typically confounded, making the theories difficult to distinguish empirically. The present research therefore used detailed computational simulations to derive contrasting predictions regarding ACC activity and error rate as a function of response speed. The simulations demonstrated a clear dissociation between conflict and error likelihood: fast response trials are associated with low conflict but high error likelihood, whereas slow response trials show the opposite pattern. Using the N2 component as an index of ACC activity, an EEG study demonstrated that when conflict and error likelihood are dissociated in this way, ACC activity tracks conflict and is negatively correlated with error likelihood. These findings support the conflict-monitoring theory and suggest that, in speeded decision tasks, ACC activity reflects current task demands rather than the retrospective coding of past performance.

Insight into the molecular mechanism of yeast acetyl-coenzyme A carboxylase mutants F510I, N485G, I69E, E477R, and K73R resistant to soraphen A

NASA Astrophysics Data System (ADS)

Gao, Jian; Liang, Li; Chen, Qingqing; Zhang, Ling; Huang, Tonghui

2018-02-01

Acetyl-coenzyme A carboxylases (ACCs) is the first committed enzyme of fatty acid synthesis pathway. The inhibition of ACC is thought to be beneficial not only for diseases related to metabolism, such as type-2 diabetes, but also for infectious disease like bacterial infection disease. Soraphen A, a potent allosteric inhibitor of BC domain of yeast ACC, exhibit lower binding affinities to several yeast ACC mutants and the corresponding drug resistance mechanisms are still unknown. We report here a theoretical study of binding of soraphen A to wild type and yeast ACC mutants (including F510I, N485G, I69E, E477R, and K73R) via molecular dynamic simulation and molecular mechanics/generalized Born surface area free energy calculations methods. The calculated binding free energies of soraphen A to yeast ACC mutants are weaker than to wild type, which is highly consistent with the experimental results. The mutant F510I weakens the binding affinity of soraphen A to yeast ACC mainly by decreasing the van der Waals contributions, while the weaker binding affinities of Soraphen A to other yeast ACC mutants including N485G, I69E, E477R, and K73R are largely attributed to the decreased net electrostatic (ΔE ele + ΔG GB) interactions. Our simulation results could provide important insights for the development of more potent ACC inhibitors.

[Cloning, expression and transcriptional analysis of biotin carboxyl carrier protein gene (accA) from Amycolatopsis mediterranei U32 ].

PubMed

Lu, Jie; Yao, Yufeng; Jiang, Weihong; Jiao, Ruishen

2003-02-01

Acetyl CoA carboxylase (EC 6.4.1.2, ACC) catalyzes the ATP-dependent carboxylation of acetyl CoA to yield malonyl CoA, which is the first committed step in fatty acid synthesis. A pair of degenerate PCR primers were designed according to the conserved amino acid sequence of AccA from M. tuberculosis and S. coelicolor. The product of the PCR amplification, a DNA fragment of 250bp was used as a probe for screening the U32 genomic cosmid library and its gene, accA, coding the biotinylated protein subunit of acetyl CoA carboxylase, was successfully cloned from U32. The accA ORF encodes a 598-amino-acid protein with the calculated molecular mass of 63.7kD, with 70.1% of G + C content. A typical Streptomyces RBS sequence, AGGAGG, was found at the - 6 position upstream of the start codon GTG. Analysis of the deduced amino acid sequence showed the presence of biotin-binding site and putative ATP-bicarbonate interaction region, which suggested the U32 AccA may act as a biotin carboxylase as well as a biotin carrier protein. Gene accA was then cloned into the pET28 (b) vector and expressed solubly in E. coli BL21 (DE3) by 0.1 mmol/L IPTG induction. Western blot confirmed the covalent binding of biotin with AccA. Northern blot analyzed transcriptional regulation of accA by 5 different nitrogen sources.

5-Hydroxytryptamine (serotonin)2A receptors in rat anterior cingulate cortex mediate the discriminative stimulus properties of d-lysergic acid diethylamide.

PubMed

Gresch, Paul J; Barrett, Robert J; Sanders-Bush, Elaine; Smith, Randy L

2007-02-01

d-Lysergic acid diethylamide (LSD), an indoleamine hallucinogen, produces profound alterations in mood, thought, and perception in humans. The brain site(s) that mediates the effects of LSD is currently unknown. In this study, we combine the drug discrimination paradigm with intracerebral microinjections to investigate the anatomical localization of the discriminative stimulus of LSD in rats. Based on our previous findings, we targeted the anterior cingulate cortex (ACC) to test its involvement in mediating the discriminative stimulus properties of LSD. Rats were trained to discriminate systemically administered LSD (0.085 mg/kg s.c.) from saline. Following acquisition of the discrimination, bilateral cannulae were implanted into the ACC (AP, +1.2 mm; ML, +/-1.0 mm; DV, -2.0 mm relative to bregma). Rats were tested for their ability to discriminate varying doses of locally infused LSD (0.1875, 0.375, and 0.75 microg/side) or artificial cerebrospinal fluid (n = 3-7). LSD locally infused into ACC dose-dependently substituted for systemically administered LSD, with 0.75 microg/side LSD substituting completely (89% correct). Systemic administration of the selective 5-hydroxytryptamine (serotonin) (5-HT)(2A) receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol (M100907; 0.4 mg/kg) blocked the discriminative cue of LSD (0.375 microg/side) infused into ACC (from 68 to 16% drug lever responding). Furthermore, M100907 (0.5 microg/microl/side) locally infused into ACC completely blocked the stimulus effects of systemic LSD (0.04 mg/kg; from 80 to 12% on the LSD lever). Taken together, these data indicate that 5-HT(2A) receptors in the ACC are a primary target mediating the discriminative stimulus properties of LSD.

Sulcal Polymorphisms of the IFC and ACC Contribute to Inhibitory Control Variability in Children and Adults

PubMed Central

Linzarini, Adriano; Dollfus, Sonia; Etard, Olivier; Orliac, François; Houdé, Olivier

2018-01-01

Abstract Inhibitory control (IC) is a core executive function that enables humans to resist habits, temptations, or distractions. IC efficiency in childhood is a strong predictor of academic and professional success later in life. Based on analysis of the sulcal pattern, a qualitative feature of cortex anatomy determined during fetal life and stable during development, we searched for evidence that interindividual differences in IC partly trace back to prenatal processes. Using anatomical magnetic resonance imaging (MRI), we analyzed the sulcal pattern of two key regions of the IC neural network, the dorsal anterior cingulate cortex (ACC) and the inferior frontal cortex (IFC), which limits the inferior frontal gyrus. We found that the sulcal pattern asymmetry of both the ACC and IFC contributes to IC (Stroop score) in children and adults: participants with asymmetrical ACC or IFC sulcal patterns had better IC efficiency than participants with symmetrical ACC or IFC sulcal patterns. Such additive effects of IFC and ACC sulcal patterns on IC efficiency suggest that distinct early neurodevelopmental mechanisms targeting different brain regions likely contribute to IC efficiency. This view shares some analogies with the “common variant–small effect” model in genetics, which states that frequent genetic polymorphisms have small effects but collectively account for a large portion of the variance. Similarly, each sulcal polymorphism has a small but additive effect: IFC and ACC sulcal patterns, respectively, explained 3% and 14% of the variance of the Stroop interference scores. PMID:29527565

Sulcal Polymorphisms of the IFC and ACC Contribute to Inhibitory Control Variability in Children and Adults.

PubMed

Tissier, Cloélia; Linzarini, Adriano; Allaire-Duquette, Geneviève; Mevel, Katell; Poirel, Nicolas; Dollfus, Sonia; Etard, Olivier; Orliac, François; Peyrin, Carole; Charron, Sylvain; Raznahan, Armin; Houdé, Olivier; Borst, Grégoire; Cachia, Arnaud

2018-01-01

Inhibitory control (IC) is a core executive function that enables humans to resist habits, temptations, or distractions. IC efficiency in childhood is a strong predictor of academic and professional success later in life. Based on analysis of the sulcal pattern, a qualitative feature of cortex anatomy determined during fetal life and stable during development, we searched for evidence that interindividual differences in IC partly trace back to prenatal processes. Using anatomical magnetic resonance imaging (MRI), we analyzed the sulcal pattern of two key regions of the IC neural network, the dorsal anterior cingulate cortex (ACC) and the inferior frontal cortex (IFC), which limits the inferior frontal gyrus. We found that the sulcal pattern asymmetry of both the ACC and IFC contributes to IC (Stroop score) in children and adults: participants with asymmetrical ACC or IFC sulcal patterns had better IC efficiency than participants with symmetrical ACC or IFC sulcal patterns. Such additive effects of IFC and ACC sulcal patterns on IC efficiency suggest that distinct early neurodevelopmental mechanisms targeting different brain regions likely contribute to IC efficiency. This view shares some analogies with the "common variant-small effect" model in genetics, which states that frequent genetic polymorphisms have small effects but collectively account for a large portion of the variance. Similarly, each sulcal polymorphism has a small but additive effect: IFC and ACC sulcal patterns, respectively, explained 3% and 14% of the variance of the Stroop interference scores.

Molecular Characterization of Lactobacillus plantarum Genes for β-Ketoacyl-Acyl Carrier Protein Synthase III (fabH) and Acetyl Coenzyme A Carboxylase (accBCDA), Which Are Essential for Fatty Acid Biosynthesis

PubMed Central

Kiatpapan, Pornpimon; Kobayashi, Hajime; Sakaguchi, Maki; Ono, Hisayo; Yamashita, Mitsuo; Kaneko, Yoshinobu; Murooka, Yoshikatsu

2001-01-01

Genes for subunits of acetyl coenzyme A carboxylase (ACC), which is the enzyme that catalyzes the first step in the synthesis of fatty acids in Lactobacillus plantarum L137, were cloned and characterized. We identified six potential open reading frames, namely, manB, fabH, accB, accC, accD, and accA, in that order. Nucleotide sequence analysis suggested that fabH encoded β-ketoacyl-acyl carrier protein synthase III, that the accB, accC, accD, and accA genes encoded biotin carboxyl carrier protein, biotin carboxylase, and the β and α subunits of carboxyltransferase, respectively, and that these genes were clustered. The organization of acc genes was different from that reported for Escherichia coli, for Bacillus subtilis, and for Pseudomonas aeruginosa. E. coli accB and accD mutations were complemented by the L. plantarum accB and accD genes, respectively. The predicted products of all five genes were confirmed by using the T7 expression system in E. coli. The gene product of accB was biotinylated in E. coli. Northern and primer extension analyses demonstrated that the five genes in L. plantarum were regulated polycistronically in an acc operon. PMID:11133475

Genetic Profile of Adenoid Cystic Carcinomas (ACC) with High-Grade Transformation versus Solid Type

PubMed Central

Costa, Ana Flávia; Altemani, Albina; Vékony, Hedy; Bloemena, Elisabeth; Fresno, Florentino; Suárez, Carlos; Llorente, José Luis; Hermsen, Mario

2010-01-01

Background: ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features and to compare results to solid ACC. Methods: Genome-wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, 4 with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), 5 solid ACC. In addition, Ki-67 index and p53 immunopositivity was assessed. Results: ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component. Conclusion: ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC. PMID:20978318

Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type.

PubMed

Costa, Ana Flávia; Altemani, Albina; Vékony, Hedy; Bloemena, Elisabeth; Fresno, Florentino; Suárez, Carlos; Llorente, José Luis; Hermsen, Mario

2010-01-01

ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features and to compare results to solid ACC. genome-wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, 4 with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), 5 solid ACC. In addition, Ki-67 index and p53 immunopositivity was assessed. ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component. ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC.

Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type.

PubMed

Costa, Ana Flávia; Altemani, Albina; Vékony, Hedy; Bloemena, Elisabeth; Fresno, Florentino; Suárez, Carlos; Llorente, José Luis; Hermsen, Mario

2011-08-01

ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features, and to compare results to solid ACC. Genome wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, four with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), and five solid ACC. In addition, Ki67 index and p53 immunopositivity was assessed. ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component. ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC.

The ability of the 2013 ACC/AHA cardiovascular risk score to identify rheumatoid arthritis patients with high coronary artery calcification scores

PubMed Central

Kawai, Vivian K.; Chung, Cecilia P.; Solus, Joseph F.; Oeser, Annette; Raggi, Paolo; Stein, C. Michael

2014-01-01

Objective Patients with rheumatoid arthritis (RA) have increased risk of atherosclerotic cardiovascular disease (ASCVD) that is underestimated by the Framingham risk score (FRS). We hypothesized that the 2013 ACC/AHA 10-year risk score would perform better than the FRS and the Reynolds risk score (RRS) in identifying RA patients known to have elevated cardiovascular risk based on high coronary artery calcification (CAC) scores. Methods Among 98 RA patients eligible for risk stratification using the ACC/AHA score we identified 34 patients with high CAC (≥ 300 Agatston units or ≥75th percentile) and compared the ability of the 10-year FRS, RRS and the ACC/AHA risk scores to correctly assign these patients to an elevated risk category. Results All three risk scores were higher in patients with high CAC (P values <0.05). The percentage of patients with high CAC correctly assigned to the elevated risk category was similar among the three scores (FRS 32%, RRS 32%, ACC/AHA 41%) (P=0.233). The c-statistics for the FRS, RRS and ACC/AHA risk scores predicting the presence of high CAC were 0.65, 0.66, and 0.65, respectively. Conclusions The ACC/AHA 10-year risk score does not offer any advantage compared to the traditional FRS and RRS in the identification of RA patients with elevated risk as determined by high CAC. The ACC/AHA risk score assigned almost 60% of patients with high CAC into a low risk category. Risk scores and standard risk prediction models used in the general population do not adequately identify many RA patients with elevated cardiovascular risk. PMID:25371313

ESO-Hα 574 and Par-Lup 3-4 jets: Exploring the spectral, kinematical, and physical properties

NASA Astrophysics Data System (ADS)

Whelan, E. T.; Bonito, R.; Antoniucci, S.; Alcalá, J. M.; Giannini, T.; Nisini, B.; Bacciotti, F.; Podio, L.; Stelzer, B.; Comerón, F.

2014-05-01

In this paper a comprehensive analysis of VLT/X-Shooter observations of two jet systems, namely ESO-Hα 574 a K8 classical T Tauri star and Par-Lup 3-4 a very low mass (0.13 M⊙) M5 star, is presented. Both stars are known to have near-edge on accretion disks. A summary of these first X-shooter observations of jets was given in a 2011 letter. The new results outlined here include flux tables of identified emission lines, information on the morphology, kinematics and physical conditions of both jets and, updated estimates of Ṁout/Ṁacc. Asymmetries in the ESO-Hα 574 flow are investigated while the Par-Lup 3-4 jet is much more symmetric. The density, temperature, and therefore origin of the gas traced by the Balmer lines are investigated from the Balmer decrements and results suggest an origin in a jet for ESO-Hα 574 while for Par-Lup 3-4 the temperature and density are consistent with an accretion flow. Ṁacc is estimated from the luminosity of various accretion tracers. For both targets, new luminosity relationships and a re-evaluation of the effect of reddening and grey extinction (due to the edge-on disks) allows for substantial improvements on previous estimates of Ṁacc. It is found that log(Ṁacc) = -9.15 ± 0.45M⊙ yr-1 and -9.30 ± 0.27M⊙ yr-1 for ESO-Hα 574 and Par-Lup 3-4 respectively. Additionally, the physical conditions in the jets (electron density, electron temperature, and ionisation) are probed using various line ratios and compared with previous determinations from iron lines. The results are combined with the luminosity of the [SII]λ6731 line to derive Ṁout through a calculation of the gas emissivity based on a 5-level atom model. As this method for deriving Ṁout comes from an exact calculation based on the jet parameters (measured directly from the spectra) rather than as was done previously from an approximate formula based on the value of the critical density at an assumed unknown temperature, values of Ṁout are far more accurate. Overall the accuracy of earlier measurements of Ṁout/Ṁacc is refined and Ṁout/Ṁacc = 0.5 (+1.0)(- 0.2) and 0.3 (+0.6)(- 0.1) for the ESO-Hα 574 red and blue jets, respectively, and 0.05 (+0.10)(- 0.02) for both the Par-Lup 3-4 red and blue jets. While the value for the total (two-sided) Ṁout/Ṁacc in ESO-Hα 574 lies outside the range predicted by magneto-centrifugal jet launching models, the errors are large and the effects of veiling and scattering on extinction measurements, and therefore the estimate of Ṁacc, should also be considered. ESO-Hα 574 is an excellent case study for understanding the impact of an edge-on accretion disk on the observed stellar emission. The improvements in the derivation of Ṁout/Ṁacc means that this ratio for Par-Lup 3-4 now lies within the range predicted by leading models, as compared to earlier measurements for very low mass stars. Par-Lup 3-4 is one of a small number of brown dwarfs and very low mass stars which launch jets. Therefore, this result is important in the context of understanding how Ṁout/Ṁacc and, thus, jet launching mechanisms for the lowest mass jet drivingsources, compare to the case of the well-studied low mass stars. Based on Observations collected with X-Shooter and UVES at the Very Large Telescope on Cerro Paranal (Chile), operated by the European Southern Observatory (ESO). Program ID's: 085.C-0238(A) and 078.C-0429(A).Appendix A is available in electronic form at http://www.aanda.org

High intensity interval training improves liver and adipose tissue insulin sensitivity

PubMed Central

Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

2015-01-01

Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307

Enhanced processing of threat stimuli under limited attentional resources.

PubMed

De Martino, Benedetto; Kalisch, Raffael; Rees, Geraint; Dolan, Raymond J

2009-01-01

The ability to process stimuli that convey potential threat, under conditions of limited attentional resources, confers adaptive advantages. This study examined the neurobiology underpinnings of this capacity. Employing an attentional blink paradigm, in conjunction with functional magnetic resonance imaging, we manipulated the salience of the second of 2 face target stimuli (T2), by varying emotionality. Behaviorally, fearful T2 faces were identified significantly more than neutral faces. Activity in fusiform face area increased with correct identification of T2 faces. Enhanced activity in rostral anterior cingulate cortex (rACC) accounted for the benefit in detection of fearful stimuli reflected in a significant interaction between target valence and correct identification. Thus, under conditions of limited attention resources activation in rACC correlated with enhanced processing of emotional stimuli. We suggest that these data support a model in which a prefrontal "gate" mechanism controls conscious access of emotional information under conditions of limited attentional resources.

Acetyl-CoA carboxylase-a as a novel target for cancer therapy.

PubMed

Wang, Chun; Rajput, Sandeep; Watabe, Kounosuke; Liao, Duan-Fang; Cao, Deliang

2010-01-01

Acetyl-CoA carboxylases (ACC) are rate-limiting enzymes in de novo fatty acid synthesis, catalyzing ATP-dependent carboxylation of acetyl-CoA to form malonyl-CoA. Malonyl-CoA is a critical bi-functional molecule, i.e., a substrate of fatty acid synthase (FAS) for acyl chain elongation (fatty acid synthesis) and an inhibitor of carnitine palmitoyltransferase I (CPT-I) for fatty acid beta-oxidation. Two ACC isoforms have been identified in mammals, i.e. ACC-alpha (ACCA, also termed ACC1) and ACC-beta (ACCB, also designated ACC2). ACC has long been used as a target for the management of metabolic diseases, such as obesity and metabolic syndrome, and various inhibitors have been developed in clinical trials. Recently, ACCA up-regulation has been recognized in multiple human cancers, promoting lipogenesis to meet the need of cancer cells for rapid growth and proliferation. Therefore, ACCA might be effective as a potent target for cancer intervention, and the inhibitors developed for the treatment of metabolic diseases would be potential therapeutic agents for cancer therapy. This review summarizes our recent findings and updates the current understanding of the ACCA with focus on cancer research.

Depression and anxious apprehension distinguish frontocingulate cortical activity during top-down attentional control.

PubMed

Silton, Rebecca Levin; Heller, Wendy; Engels, Anna S; Towers, David N; Spielberg, Jeffrey M; Edgar, J Christopher; Sass, Sarah M; Stewart, Jennifer L; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

2011-05-01

A network consisting of left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC) has been implicated in top-down attentional control. Few studies have systematically investigated how this network is altered in psychopathology, despite evidence that depression and anxiety are associated with attentional control impairments. Functional MRI and dense-array event-related brain potential (ERP) data were collected in separate sessions from 100 participants during a color-word Stroop task. Functional MRI results guided ERP source modeling to characterize the time course of activity in LDLPFC (300-440 ms) and dACC (520-680 ms). At low levels of depression, LDLPFC activity was indirectly related to Stroop interference and only via dACC activity. In contrast, at high levels of depression, dACC did not play an intervening role, and increased LDLPFC activity was directly related to decreased Stroop interference. Specific to high levels of anxious apprehension, higher dACC activity was related to more Stroop interference. Results indicate that depression and anxious apprehension modulate temporally and functionally distinct aspects of the frontocingulate network involved in top-down attention control.

Anterior cingulate cortex-related connectivity in first-episode schizophrenia: a spectral dynamic causal modeling study with functional magnetic resonance imaging

PubMed Central

Cui, Long-Biao; Liu, Jian; Wang, Liu-Xian; Li, Chen; Xi, Yi-Bin; Guo, Fan; Wang, Hua-Ning; Zhang, Lin-Chuan; Liu, Wen-Ming; He, Hong; Tian, Ping; Yin, Hong; Lu, Hongbing

2015-01-01

Understanding the neural basis of schizophrenia (SZ) is important for shedding light on the neurobiological mechanisms underlying this mental disorder. Structural and functional alterations in the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, and medial prefrontal cortex (MPFC) have been implicated in the neurobiology of SZ. However, the effective connectivity among them in SZ remains unclear. The current study investigated how neuronal pathways involving these regions were affected in first-episode SZ using functional magnetic resonance imaging (fMRI). Forty-nine patients with a first-episode of psychosis and diagnosis of SZ—according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision—were studied. Fifty healthy controls (HCs) were included for comparison. All subjects underwent resting state fMRI. We used spectral dynamic causal modeling (DCM) to estimate directed connections among the bilateral ACC, DLPFC, hippocampus, and MPFC. We characterized the differences using Bayesian parameter averaging (BPA) in addition to classical inference (t-test). In addition to common effective connectivity in these two groups, HCs displayed widespread significant connections predominantly involved in ACC not detected in SZ patients, but SZ showed few connections. Based on BPA results, SZ patients exhibited anterior cingulate cortico-prefrontal-hippocampal hyperconnectivity, as well as ACC-related and hippocampal-dorsolateral prefrontal-medial prefrontal hypoconnectivity. In summary, spectral DCM revealed the pattern of effective connectivity involving ACC in patients with first-episode SZ. This study provides a potential link between SZ and dysfunction of ACC, creating an ideal situation to associate mechanisms behind SZ with aberrant connectivity among these cognition and emotion-related regions. PMID:26578933

A Chemogenomic Screen Reveals Novel Snf1p/AMPK Independent Regulators of Acetyl-CoA Carboxylase.

PubMed

Bozaquel-Morais, Bruno L; Madeira, Juliana B; Venâncio, Thiago M; Pacheco-Rosa, Thiago; Masuda, Claudio A; Montero-Lomeli, Monica

2017-01-01

Acetyl-CoA carboxylase (Acc1p) is a key enzyme in fatty acid biosynthesis and is essential for cell viability. To discover new regulators of its activity, we screened a Saccharomyces cerevisiae deletion library for increased sensitivity to soraphen A, a potent Acc1p inhibitor. The hits identified in the screen (118 hits) were filtered using a chemical-phenotype map to exclude those associated with pleiotropic drug resistance. This enabled the identification of 82 ORFs that are genetic interactors of Acc1p. The main functional clusters represented by these hits were "transcriptional regulation", "protein post-translational modifications" and "lipid metabolism". Further investigation of the "transcriptional regulation" cluster revealed that soraphen A sensitivity is poorly correlated with ACC1 transcript levels. We also studied the three top unknown ORFs that affected soraphen A sensitivity: SOR1 (YDL129W), SOR2 (YIL092W) and SOR3 (YJR039W). Since the C18/C16 ratio of lipid acyl lengths reflects Acc1p activity levels, we evaluated this ratio in the three mutants. Deletion of SOR2 and SOR3 led to reduced acyl lengths, suggesting that Acc1p is indeed down-regulated in these strains. Also, these mutants showed no differences in Snf1p/AMPK activation status and deletion of SNF1 in these backgrounds did not revert soraphen A sensitivity completely. Furthermore, plasmid maintenance was reduced in sor2Δ strain and this trait was shared with 18 other soraphen A sensitive hits. In summary, our screen uncovered novel Acc1p Snf1p/AMPK-independent regulators.

The roles of the anterior cingulate cortex and its dopamine receptors in self-paced cost-benefit decision making in rats.

PubMed

Wang, Shuai; Hu, Shan-Hu; Shi, Yi; Li, Bao-Ming

2017-03-01

It has been shown that the anterior cingulate cortex (ACC) and its dopamine system are crucial for decision making that requires physical/emotional effort, but not for all forms of cost-benefit decision making. Previous studies had mostly employed behavioral tasks with two competing cost-reward options that were preset by the experimenters. However, few studies have been conducted using scenarios in which the subjects have full control over the energy/time expenditure required to obtain a proportional reward. Here, we assessed the roles of the ACC and its dopamine system in cost-benefit decision making by utilizing a "do more get more" (DMGM) task and a time-reward trade-off (TRTO) task, wherein the animals were able to self-determine how much effort or time to expend at a nosepoke operandum for a proportional reward. Our results showed that (1) ACC inactivation severely impaired DMGM task performance, with a reduction in the rate of correct responses and a decrease in the effort expended, but did not affect the TRTO task; and (2) blocking ACC D2 receptors had no impact on DMGM task performance in the baseline cost-benefit scenario, but it significantly reduced the attempts to invest increased effort for a large reward when the benefit-cost ratio was reduced by half. In contrast, blocking ACC D1 receptors had no effect on DMGM task performance. These findings suggest that the ACC is required for self-paced effort-based but not for time-reward trade-off decision making. Furthermore, ACC dopamine D2 but not D1 receptors are involved in DMGM decision making.

A Pyranose-2-Phosphate Motif Is Responsible for Both Antibiotic Import and Quorum-Sensing Regulation in Agrobacterium tumefaciens

PubMed Central

El Sahili, Abbas; Li, Si-Zhe; Lang, Julien; Virus, Cornelia; Planamente, Sara; Ahmar, Mohammed; Guimaraes, Beatriz G.; Aumont-Nicaise, Magali; Vigouroux, Armelle; Soulère, Laurent; Reader, John; Queneau, Yves; Faure, Denis; Moréra, Solange

2015-01-01

Periplasmic binding proteins (PBPs) in association with ABC transporters select and import a wide variety of ligands into bacterial cytoplasm. They can also take up toxic molecules, as observed in the case of the phytopathogen Agrobacterium tumefaciens strain C58. This organism contains a PBP called AccA that mediates the import of the antibiotic agrocin 84, as well as the opine agrocinopine A that acts as both a nutrient and a signalling molecule for the dissemination of virulence genes through quorum-sensing. Here, we characterized the binding mode of AccA using purified agrocin 84 and synthetic agrocinopine A by X-ray crystallography at very high resolution and performed affinity measurements. Structural and affinity analyses revealed that AccA recognizes an uncommon and specific motif, a pyranose-2-phosphate moiety which is present in both imported molecules via the L-arabinopyranose moiety in agrocinopine A and the D-glucopyranose moiety in agrocin 84. We hypothesized that AccA is a gateway allowing the import of any compound possessing a pyranose-2-phosphate motif at one end. This was structurally and functionally confirmed by experiments using four synthetic compounds: agrocinopine 3’-O-benzoate, L-arabinose-2-isopropylphosphate, L-arabinose-2-phosphate and D-glucose-2-phosphate. By combining affinity measurements and in vivo assays, we demonstrated that both L-arabinose-2-phosphate and D-glucose-2-phosphate, which are the AccF mediated degradation products of agrocinopine A and agrocin 84 respectively, interact with the master transcriptional regulator AccR and activate the quorum-sensing signal synthesis and Ti plasmid transfer in A. tumefaciens C58. Our findings shed light on the role of agrocinopine and antibiotic agrocin 84 on quorum-sensing regulation in A. tumefaciens and reveal how the PBP AccA acts as vehicle for the importation of both molecules by means of a key-recognition motif. It also opens future possibilities for the rational design of antibiotic and anti-virulence compounds against A. tumefaciens or other pathogens possessing similar PBPs. PMID:26244338

A Pyranose-2-Phosphate Motif Is Responsible for Both Antibiotic Import and Quorum-Sensing Regulation in Agrobacterium tumefaciens.

PubMed

El Sahili, Abbas; Li, Si-Zhe; Lang, Julien; Virus, Cornelia; Planamente, Sara; Ahmar, Mohammed; Guimaraes, Beatriz G; Aumont-Nicaise, Magali; Vigouroux, Armelle; Soulère, Laurent; Reader, John; Queneau, Yves; Faure, Denis; Moréra, Solange

2015-08-01

Periplasmic binding proteins (PBPs) in association with ABC transporters select and import a wide variety of ligands into bacterial cytoplasm. They can also take up toxic molecules, as observed in the case of the phytopathogen Agrobacterium tumefaciens strain C58. This organism contains a PBP called AccA that mediates the import of the antibiotic agrocin 84, as well as the opine agrocinopine A that acts as both a nutrient and a signalling molecule for the dissemination of virulence genes through quorum-sensing. Here, we characterized the binding mode of AccA using purified agrocin 84 and synthetic agrocinopine A by X-ray crystallography at very high resolution and performed affinity measurements. Structural and affinity analyses revealed that AccA recognizes an uncommon and specific motif, a pyranose-2-phosphate moiety which is present in both imported molecules via the L-arabinopyranose moiety in agrocinopine A and the D-glucopyranose moiety in agrocin 84. We hypothesized that AccA is a gateway allowing the import of any compound possessing a pyranose-2-phosphate motif at one end. This was structurally and functionally confirmed by experiments using four synthetic compounds: agrocinopine 3'-O-benzoate, L-arabinose-2-isopropylphosphate, L-arabinose-2-phosphate and D-glucose-2-phosphate. By combining affinity measurements and in vivo assays, we demonstrated that both L-arabinose-2-phosphate and D-glucose-2-phosphate, which are the AccF mediated degradation products of agrocinopine A and agrocin 84 respectively, interact with the master transcriptional regulator AccR and activate the quorum-sensing signal synthesis and Ti plasmid transfer in A. tumefaciens C58. Our findings shed light on the role of agrocinopine and antibiotic agrocin 84 on quorum-sensing regulation in A. tumefaciens and reveal how the PBP AccA acts as vehicle for the importation of both molecules by means of a key-recognition motif. It also opens future possibilities for the rational design of antibiotic and anti-virulence compounds against A. tumefaciens or other pathogens possessing similar PBPs.

An improved understanding of the Alaska coastal current: The application of a bivalve growth-temperature model to reconstruct freshwater-influenced paleoenvironments

USGS Publications Warehouse

Hallmann, N.; Schone, B.R.; Irvine, G.V.; Burchell, M.; Cokelet, E.D.; Hilton, M.R.

2011-01-01

Shells of intertidal bivalve mollusks contain sub-seasonally to interannually resolved records of temperature and salinity variations in coastal settings. Such data are essential to understand changing land-sea interactions through time, specifically atmospheric (precipitation rate, glacial meltwater, river discharge) and oceanographic circulation patterns; however, independent temperature and salinity proxies are currently not available. We established a model for reconstructing daily water temperatures with an average standard error of ???1.3 ??C based on variations in the width of lunar daily growth increments of Saxidomus gigantea from southwestern Alaska, United States. Temperature explains 70% of the variability in shell growth. When used in conjunction with stable oxygen isotope data, this approach can also be used to identify changes in past seawater salinity. This study provides a better understanding of the hydrological changes related to the Alaska Coastal Current (ACC). In combination with ??18Oshell values, increment-derived temperatures were used to estimate salinity changes with an average error of 1.4 ?? 1.1 PSU. Our model was calibrated and tested with modern shells and then applied to archaeological specimens. As derived from the model, the time interval of 988-1447 cal yr BP was characterized by ???1-2 ??C colder and much drier (2-5 PSU) summers. During that time, the ACC was likely flowing much more slowly than at present. In contrast, between 599-1014 cal yr BP, the Aleutian low may have been stronger, which resulted in a 3 ??C temperature decrease during summers and 1-2 PSU fresher conditions than today; the ACC was probably flowing more quickly at that time. The shell growth-temperature model can be used to estimate seasonal to interannual salinity and temperature changes in freshwater-influenced environments through time. ?? 2011 SEPM (Society for Sedimentary Geology).

Global climate simulations at 3000-year intervals for the last 21 000 years with the GENMOM coupled atmosphere–ocean model

USGS Publications Warehouse

Alder, Jay R.; Hostetler, Steven W.

2015-01-01

We apply GENMOM, a coupled atmosphere–ocean climate model, to simulate eight equilibrium time slices at 3000-year intervals for the past 21 000 years forced by changes in Earth–Sun geometry, atmospheric greenhouse gases (GHGs), continental ice sheets, and sea level. Simulated global cooling during the Last Glacial Maximum (LGM) is 3.8 ◦C and the rate of post-glacial warming is in overall agreement with recently published temperature reconstructions. The greatest rate of warming occurs between 15 and 12 ka (2.4 ◦C over land, 0.7 ◦C over oceans, and 1.4 ◦C globally) in response to changes in radiative forcing from the diminished extent of the Northern Hemisphere (NH) ice sheets and increases in GHGs and NH summer insolation. The modeled LGM and 6 ka temperature and precipitation climatologies are generally consistent with proxy reconstructions, the PMIP2 and PMIP3 simulations, and other paleoclimate data–model analyses. The model does not capture the mid-Holocene “thermal maximum” and gradual cooling to preindustrial (PI) global temperature found in the data. Simulated monsoonal precipitation in North Africa peaks between 12 and 9 ka at values ∼ 50 % greater than those of the PI, and Indian monsoonal precipitation peaks at 12 and 9 ka at values ∼ 45 % greater than the PI. GENMOM captures the reconstructed LGM extent of NH and Southern Hemisphere (SH) sea ice. The simulated present-day Antarctica Circumpolar Current (ACC) is ∼ 48 % weaker than the observed (62 versus 119 Sv). The simulated present-day Atlantic Meridional Overturning Circulation (AMOC) of 19.3 ± 1.4 Sv on the Bermuda Rise (33◦ N) is comparable with observed value of 18.7 ± 4.8 Sv. AMOC at 33◦ N is reduced by ∼ 15 % during the LGM, and the largest post-glacial increase (∼ 11 %) occurs during the 15 ka time slice.

AMPK activation represses the human gene promoter of the cardiac isoform of acetyl-CoA carboxylase: Role of nuclear respiratory factor-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adam, Tasneem; Opie, Lionel H.; Essop, M. Faadiel, E-mail: mfessop@sun.ac.za

Research highlights: {yields} AMPK inhibits acetyl-CoA carboxylase beta gene promoter activity. {yields} Nuclear respiratory factor-1 inhibits acetyl-CoA carboxylase beta promoter activity. {yields} AMPK regulates acetyl-CoA carboxylase beta at transcriptional level. -- Abstract: The cardiac-enriched isoform of acetyl-CoA carboxylase (ACC{beta}) produces malonyl-CoA, a potent inhibitor of carnitine palmitoyltransferase-1. AMPK inhibits ACC{beta} activity, lowering malonyl-CoA levels and promoting mitochondrial fatty acid {beta}-oxidation. Previously, AMPK increased promoter binding of nuclear respiratory factor-1 (NRF-1), a pivotal transcriptional modulator controlling gene expression of mitochondrial proteins. We therefore hypothesized that NRF-1 inhibits myocardial ACC{beta} promoter activity via AMPK activation. A human ACC{beta} promoter-luciferase construct was transientlymore » transfected into neonatal cardiomyocytes {+-} a NRF-1 expression construct. NRF-1 overexpression decreased ACC{beta} gene promoter activity by 71 {+-} 4.6% (p < 0.001 vs. control). Transfections with 5'-end serial promoter deletions revealed that NRF-1-mediated repression of ACC{beta} was abolished with a pPII{beta}-18/+65-Luc deletion construct. AMPK activation dose-dependently reduced ACC{beta} promoter activity, while NRF-1 addition did not further decrease it. We also investigated NRF-1 inhibition in the presence of upstream stimulatory factor 1 (USF1), a known transactivator of the human ACC{beta} gene promoter. Here NRF-1 blunted USF1-dependent induction of ACC{beta} promoter activity by 58 {+-} 7.5% (p < 0.001 vs. control), reversed with a dominant negative NRF-1 construct. NRF-1 also suppressed endogenous USF1 transcriptional activity by 55 {+-} 6.2% (p < 0.001 vs. control). This study demonstrates that NRF-1 is a novel transcriptional inhibitor of the human ACC{beta} gene promoter in the mammalian heart. Our data extends AMPK regulation of ACC{beta} to the transcriptional level.« less

Test Rig for Evaluating Active Turbine Blade Tip Clearance Control Concepts

NASA Technical Reports Server (NTRS)

Lattime, Scott B.; Steinetz, Bruce M.; Robbie, Malcolm G.; Erker, Arthur H.

2004-01-01

The objectives of the research presented in this viewgraph presentation are to 1) Design a mechanical ACC system for HPT tip seal clearance management; 2) Design a test rig to evaluate ACC system concepts. We have focused our efforts on designing mechanical ACC systems that articulate the seal shroud via mechanical linkages connected to actuators that reside outside the extreme environment of the HPT. We opted for this style of design due to a lack of high temperature/low profile actuators that are presently available. We have also selected multiple hydraulic actuators for this first generation ACC system. Fuel-draulic actuators are already a well established technology.

GPACC program cost work breakdown structure-dictionary. General purpose aft cargo carrier study, volume 3

NASA Technical Reports Server (NTRS)

1985-01-01

The results of detailed cost estimates and economic analysis performed on the updated Model 101 configuration of the general purpose Aft Cargo Carrier (ACC) are given. The objective of this economic analysis is to provide the National Aeronautics and Space Administration (NASA) with information on the economics of using the ACC on the Space Transportation System (STS). The detailed cost estimates for the ACC are presented by a work breakdown structure (WBS) to ensure that all elements of cost are considered in the economic analysis and related subsystem trades. Costs reported by WBS provide NASA with a basis for comparing competing designs and provide detailed cost information that can be used to forecast phase C/D planning for new projects or programs derived from preliminary conceptual design studies. The scope covers all STS and STS/ACC launch vehicle cost impacts for delivering payloads to a 160 NM low Earth orbit (LEO).

Effect of the Age Cross-Link Breaker Alagebrium on Anterior Segment Physiology, Morphology, and Ocular Age and Rage

PubMed Central

Kiland, Julie A.; Gabelt, B’Ann T.; Tezel, Gülgün; Lütjen-Drecoll, Elke; Kaufman, Paul L.

2009-01-01

Purpose: To determine the effects of the advanced glycation end product (AGE) cross-link breaker alagebrium on intraocular pressure (IOP), accommodation (ACC), outflow facility (OF), anterior segment morphology, and ocular AGE and receptors for AGE (RAGE) in older rhesus monkeys. Methods: Six rhesus monkeys (aged 19 to 20 years) received 3 or 4 intracameral and intravitreal (final concentration, 1 mM) injections of alagebrium to one eye over 2.5 to 3 weeks and vehicle to the opposite eye. ACC and OF responses to intramuscular or intravenous pilocarpine were measured at baseline and at 1 to 2 weeks and 2, 4, and 6 months postinjection. IOP was measured prior to all injections, ACC, and OF measurements. Monkeys were euthanized 3 to 6 months after the last injection, the eyes were enucleated, and anterior and posterior segments were examined by electron microscopy or immunohistochemistry. Results: No significant differences were found in ACC or IOP at any time point after alagebrium treatment. Baseline OF was higher (37.0 ± 6.0%; P ≤ .005) in alagebrium-treated vs control eyes at 6 months postinjection. In 3 monkeys, alagebrium-treated eyes, compared to control eyes, showed greater focal plaque formation, similar to that seen in primary open-angle glaucoma, in the juxtacanalicular meshwork/inner wall of Schlemm’s canal. No changes in anterior segment AGE or RAGE were detectable. However, some areas of the retina and optic nerve head exhibited decreased AGE and increased RAGE immunostaining. Conclusions: Intraocular injection of AGE cross-link breakers is an unlikely approach for glaucoma therapy. However, it may generate a model for further study of glaucomatous-like plaque formation. Immunohistochemical changes in the posterior segment in response to alagebrium warrant further functional studies. PMID:20126491

Mentoring in 2 + 2 Programs: LISD/ACC 2 + 2 Articulation Project.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

The role of mentoring in the 2 + 2 Instrumentation and Control (I&C) articulation project between the Leander Independent School District (LISD) and Austin Community College (ACC) is discussed in this document. Following a brief history of the origin and function of the mentor, the paper explains the need for the mentoring system in the I&C…

Cellulose nanofibers isolated by TEMPO-oxidation and aqueous counter collision methods.

PubMed

Van Hai, Le; Zhai, Lindong; Kim, Hyun Chan; Kim, Jung Woong; Choi, Eun Sik; Kim, Jaehwan

2018-07-01

In this research, cellulose nanofiber (CNF) was isolated by the combination of chemical 2,2,6,6-tetramethylpiperidine-1-oxylradical (TEMPO)-oxidation and physical aqueous counter collision (ACC) methods The combination of TEMPO-oxidation and ACC is an efficient method to isolate CNFs by reducing chemical usage in TEMPO-oxidation and saving energy in ACC along with controlling the size of CNFs. Two cellulose sources, hardwood bleached kraft pulp (HW) and softwood bleached kraft pulp (SW), were used for the CNF isolation with different TEMPO oxidation time and a defined number of ACC pass. The CNF properties were investigated and compared in term of morphology, crystallinity index, transparency and birefringence. The width of the isolated CNFs from HW is in the range of 15.1 nm-17.5 nm, and that of the SW CNFs is between 18.4 nm and 22 nm depending on the TEMPO oxidation time. This difference is due to the fact that SW is less oxidized than HW under the same chemical dosage, which results in larger width of SW-CNFs than HW-CNFs. The HW-CNF treated with TEMPO for over 2 h and isolated using ACC with 5 pass offers almost 90% transparency. Birefringence of CNFs exhibits that HW-CNFs show better birefringence phenomenon than SW-CNFs. The combination of TEMPO-oxidation and ACC methods is useful for isolating CNFs with its size control. Copyright © 2018 Elsevier Ltd. All rights reserved.

The rhizobacterium Variovorax paradoxus 5C-2, containing ACC deaminase, promotes growth and development of Arabidopsis thaliana via an ethylene-dependent pathway

PubMed Central

Dodd, Ian C.

2013-01-01

Many plant-growth-promoting rhizobacteria (PGPR) associated with plant roots contain the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase and can metabolize ACC, the immediate precursor of the plant hormone ethylene, thereby decreasing plant ethylene production and increasing plant growth. However, relatively few studies have explicitly linked ethylene emission and/or action to growth promotion in these plant–microbe interactions. This study examined effects of the PGPR Variovorax paradoxus 5C-2 containing ACC deaminase on the growth and development of Arabidopsis thaliana using wild-type (WT) plants and several ethylene-related mutants (etr1-1, ein2-1, and eto1-1). Soil inoculation with V. paradoxus 5C-2 promoted growth (leaf area and shoot biomass) of WT plants and the ethylene-overproducing mutant eto1-1, and also enhanced floral initiation of WT plants by 2.5 days. However, these effects were not seen in ethylene-insensitive mutants (etr1-1 and ein2-1) even though bacterial colonization of the root system was similar. Furthermore, V. paradoxus 5C-2 decreased ACC concentrations of rosette leaves of WT plants by 59% and foliar ethylene emission of both WT plants and eto1-1 mutants by 42 and 37%, respectively. Taken together, these results demonstrate that a fully functional ethylene signal transduction pathway is required for V. paradoxus 5C-2 to stimulate leaf growth and flowering of A. thaliana. PMID:23404897

The rhizobacterium Variovorax paradoxus 5C-2, containing ACC deaminase, promotes growth and development of Arabidopsis thaliana via an ethylene-dependent pathway.

PubMed

Chen, Lin; Dodd, Ian C; Theobald, Julian C; Belimov, Andrey A; Davies, William J

2013-04-01

Many plant-growth-promoting rhizobacteria (PGPR) associated with plant roots contain the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase and can metabolize ACC, the immediate precursor of the plant hormone ethylene, thereby decreasing plant ethylene production and increasing plant growth. However, relatively few studies have explicitly linked ethylene emission and/or action to growth promotion in these plant-microbe interactions. This study examined effects of the PGPR Variovorax paradoxus 5C-2 containing ACC deaminase on the growth and development of Arabidopsis thaliana using wild-type (WT) plants and several ethylene-related mutants (etr1-1, ein2-1, and eto1-1). Soil inoculation with V. paradoxus 5C-2 promoted growth (leaf area and shoot biomass) of WT plants and the ethylene-overproducing mutant eto1-1, and also enhanced floral initiation of WT plants by 2.5 days. However, these effects were not seen in ethylene-insensitive mutants (etr1-1 and ein2-1) even though bacterial colonization of the root system was similar. Furthermore, V. paradoxus 5C-2 decreased ACC concentrations of rosette leaves of WT plants by 59% and foliar ethylene emission of both WT plants and eto1-1 mutants by 42 and 37%, respectively. Taken together, these results demonstrate that a fully functional ethylene signal transduction pathway is required for V. paradoxus 5C-2 to stimulate leaf growth and flowering of A. thaliana.

Glutamatergic and neurometabolic alterations in chronic cocaine users measured with (1) H-magnetic resonance spectroscopy.

PubMed

Hulka, Lea M; Scheidegger, Milan; Vonmoos, Matthias; Preller, Katrin H; Baumgartner, Markus R; Herdener, Marcus; Seifritz, Erich; Henning, Anke; Quednow, Boris B

2016-01-01

Cocaine addiction is a chronically relapsing disorder that is associated with harmful consequences. Relapses occur frequently and effective pharmacotherapies are currently sparse. Preclinical studies suggest that altered glutamatergic signaling is crucial for the maintenance of cocaine self-administration. However, the translational validity of these models is currently unknown. Therefore, we investigated potential differences of glutamate, glutamine and further metabolite levels in the pregenual anterior cingulate cortex (pgACC) and the right dorsolateral prefrontal cortex (rDLPFC) of chronic cocaine users and controls using the PRior knOwledge FITting 2.0 tool in combination with two-dimensional J-resolved single-voxel (1) H-magnetic resonance spectroscopy at 3T and voxel tissue composition and relaxation correction. Glutamate and glutamine levels did not differ between cocaine users and controls, but higher weekly cocaine use and higher cocaine hair concentrations were associated with lower glutamine/creatine ratios in the pgACC. Interestingly, cocaine users exhibited higher glucose/total creatine ratios than controls in the pgACC and higher choline/creatine ratios in the pgACC and rDLPFC. These results imply that cocaine use is associated with altered cortical glucose metabolism and membrane turnover. Finally, cocaine use over the past 6 months appears to decrease cortical glutamine levels indicating changes in glutamate cycling. © 2014 Society for the Study of Addiction.

A colorimetric assay of 1-aminocyclopropane-1-carboxylate (ACC) based on ninhydrin reaction for rapid screening of bacteria containing ACC deaminase.

PubMed

Li, Z; Chang, S; Lin, L; Li, Y; An, Q

2011-08-01

1-Aminocyclopropane-1-carboxylate (ACC) deaminase activity is an efficient marker for bacteria to promote plant growth by lowering ethylene levels in plants. We aim to develop a method for rapidly screening bacteria containing ACC deaminase, based on a colorimetric ninhydrin assay of ACC. A reliable colorimetric ninhydrin assay was developed to quantify ACC using heat-resistant polypropylene chimney-top 96-well PCR plates, having the wells evenly heated in boiling water, preventing accidental contamination from boiling water and limiting evaporation. With this method to measure bacterial consumption of ACC, 44 ACC-utilizing bacterial isolates were rapidly screened out from 311 bacterial isolates that were able to grow on minimal media containing ACC as the sole nitrogen source. The 44 ACC-utilizing bacterial isolates showed ACC deaminase activities and belonged to the genus Burkholderia, Pseudomonas or Herbaspirillum. Determination of bacterial ACC consumption by the PCR-plate ninhydrin-ACC assay is a rapid and efficient method for screening bacteria containing ACC deaminase from a large number of bacterial isolates. The PCR-plate ninhydrin-ACC assay extends the utility of the ninhydrin reaction and enables a rapid screening of bacteria containing ACC deaminase from large numbers of bacterial isolates. © 2011 The Authors. Letters in Applied Microbiology © 2011 The Society for Applied Microbiology.

2013 ACC/AHA Cholesterol Guideline Versus 2004 NCEP ATP III Guideline in the Prediction of Coronary Artery Calcification Progression in a Korean Population.

PubMed

Cho, Yun Kyung; Jung, Chang Hee; Kang, Yu Mi; Hwang, Jenie Yoonoo; Kim, Eun Hee; Yang, Dong Hyun; Kang, Joon-Won; Park, Joong-Yeol; Kim, Hong-Kyu; Lee, Woo Je

2016-08-19

Since the release of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, significant controversy has surrounded the applicability of the new cholesterol guidelines and the Pooled Cohort Equations. In this present study, we investigated whether eligibility for statin therapy determined by the 2013 ACC/AHA guidelines on the management of blood cholesterol is better aligned with the progression of coronary artery calcification (CAC) detected by coronary computed tomography angiography (CCTA) than the previously recommended 2004 National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines. We enrolled 1246 asymptomatic participants who underwent repeated CAC score measurement during routine health examinations. The CAC score progression was defined as either incident CAC in a population free of CAC at baseline or increase ≥2.5 units between the baseline and final square root of CAC scores participants who had detectable CAC at baseline examination. Application of the ACC/AHA guidelines to the study population increased the proportion of statin-eligible subjects from 20.5% (according to ATP III) to 54.7%. Statin-eligible subjects, as defined by ACC/AHA guidelines, showed a higher odds ratio for CAC score progression than those considered statin eligible according to ATP III guidelines (2.73 [95% CI, 2.07-3.61] vs 2.00 [95% CI, 1.49-2.68]). Compared with the ATP III guidelines, the new ACC/AHA guidelines result in better discrimination of subjects with cardiovascular risk detected by CAC score progression in an Asian population. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Study binding of Al-curcumin complex to ds-DNA, monitoring by multispectroscopic and voltammetric techniques

NASA Astrophysics Data System (ADS)

Ahmadi, F.; Alizadeh, A. A.; Shahabadi, N.; Rahimi-Nasrabadi, M.

2011-09-01

In this work a complex of Al 3+ with curcumin ([Al(curcumin) (EtOH) 2](NO 3) 2) was synthesized and characterized by UV-vis, FT-IR, elemental analysis and spectrophotometric titration techniques. The mole ratio plot revealed a 1:1 complex between Al 3+ and curcumin in solution. For binding studies of this complex to calf thymus-DNA various methods such as: UV-vis, fluorescence, circular dichroism (CD), FT-IR spectroscopy and cyclic voltammetry were used. The intrinsic binding constant of ACC with DNA at 25 °C was calculated by UV-vis and cyclic voltammetry as 2.1 × 10 4 and 2.6 × 10 4, respectively. The thermodynamic studies showed that the reaction is enthalpy and entropy favored. The CD results showed that only the Δ-ACC interacts with DNA and the Δ-ACC form has not any tendency to interact with DNA, also the pure curcumin has not any stereoselective interaction with CT-DNA. Fluorimetric studies showed that fluorescence enhancement was initiated by a static process in the ground state. The cyclic voltammetry showed that ACC interact with DNA with a binding site size of 2. From the FT-IR we concluded that the Δ-ACC interacts with DNA via partial electrostatic and minor groove binding. In comparison with previous works it was concluded that curcumin significantly reduced the affinity of Al 3+ to the DNA.

Meridional circulation across the Antarctic Circumpolar Current serves as a double 231Pa and 230Th trap

NASA Astrophysics Data System (ADS)

Rutgers van der Loeff, Michiel; Venchiarutti, Celia; Stimac, Ingrid; van Ooijen, Jan; Huhn, Oliver; Rohardt, Gerd; Strass, Volker

2016-12-01

Upwelling of Circumpolar Deep Water in the Weddell Gyre and low scavenging rates south of the Antarctic Circumpolar Current (ACC) cause an accumulation of particle reactive nuclides in the Weddell Gyre. A ventilation/reversible scavenging model that successfully described the accumulation of 230Th in this area was tested with other particle reactive nuclides and failed to adequately describe the depth-distributions of 231Pa and 210Pb. We present here a modified model that includes a nutrient-like accumulation south of the Antarctic Polar Front in an upper meridional circulation cell, as well as transport to a deep circulation cell in the Weddell Gyre by scavenging and subsequent release at depth. The model also explains depletion of 231Pa and 230Th in Weddell Sea Bottom Water (WSBW) by ventilation of newly formed deep water on a timescale of 10 years, but this water mass is too dense to leave the Weddell Gyre. In order to quantify the processes responsible for the 231Pa- and 230Th-composition of newly formed Antarctic Bottom Water (AABW) we present a mass balance of 231Pa and 230Th in the Atlantic sector of the Southern Ocean based on new data from the GEOTRACES program. The ACC receives 6.0 ± 1.5 ×106 dpms-1 of 230Th from the Weddell Sea, similar in magnitude to the net input of 4.2 ± 3.0 ×106 dpms-1 from the north. For 231Pa, the relative contribution from the Weddell Sea is much smaller, only 0.3 ± 0.1 ×106, compared to 2.7 ± 1.4 ×106 dpms-1 from the north. Weddell Sea Deep Water (WSDW) leaving the Weddell Gyre northward to form AABW is exposed in the ACC to resuspended opal-rich sediments that act as efficient scavengers with a Th/Pa fractionation factor F ≤ 1. Hydrothermal inputs may provide additional removal with low F. Scavenging in the full meridional circulation across the opal-rich ACC thus acts as a double 231Pa and 230Th trap that preconditions newly formed AABW.

Neurons in Dorsal Anterior Cingulate Cortex Signal Postdecisional Variables in a Foraging Task

PubMed Central

Hayden, Benjamin Y.

2014-01-01

The dorsal anterior cingulate cortex (dACC) is a key hub of the brain's executive control system. Although a great deal is known about its role in outcome monitoring and behavioral adjustment, whether and how it contributes to the decision process remain unclear. Some theories suggest that dACC neurons track decision variables (e.g., option values) that feed into choice processes and is thus “predecisional.” Other theories suggest that dACC activity patterns differ qualitatively depending on the choice that is made and is thus “postdecisional.” To compare these hypotheses, we examined responses of 124 dACC neurons in a simple foraging task in which monkeys accepted or rejected offers of delayed rewards. In this task, options that vary in benefit (reward size) and cost (delay) appear for 1 s; accepting the option provides the cued reward after the cued delay. To get at dACC neurons' contributions to decisions, we focused on responses around the time of choice, several seconds before the reward and the end of the trial. We found that dACC neurons signal the foregone value of the rejected option, a postdecisional variable. Neurons also signal the profitability (that is, the relative value) of the offer, but even these signals are qualitatively different on accept and reject decisions, meaning that they are also postdecisional. These results suggest that dACC can be placed late in the decision process and also support models that give it a regulatory role in decision, rather than serving as a site of comparison. PMID:24403162

Projective rectification of infrared images from air-cooled condenser temperature measurement by using projection profile features and cross-ratio invariability.

PubMed

Xu, Lijun; Chen, Lulu; Li, Xiaolu; He, Tao

2014-10-01

In this paper, we propose a projective rectification method for infrared images obtained from the measurement of temperature distribution on an air-cooled condenser (ACC) surface by using projection profile features and cross-ratio invariability. In the research, the infrared (IR) images acquired by the four IR cameras utilized are distorted to different degrees. To rectify the distorted IR images, the sizes of the acquired images are first enlarged by means of bicubic interpolation. Then, uniformly distributed control points are extracted in the enlarged images by constructing quadrangles with detected vertical lines and detected or constructed horizontal lines. The corresponding control points in the anticipated undistorted IR images are extracted by using projection profile features and cross-ratio invariability. Finally, a third-order polynomial rectification model is established and the coefficients of the model are computed with the mapping relationship between the control points in the distorted and anticipated undistorted images. Experimental results obtained from an industrial ACC unit show that the proposed method performs much better than any previous method we have adopted. Furthermore, all rectified images are stitched together to obtain a complete image of the whole ACC surface with a much higher spatial resolution than that obtained by using a single camera, which is not only useful but also necessary for more accurate and comprehensive analysis of ACC performance and more reliable optimization of ACC operations.

Assay Methods for ACS Activity and ACS Phosphorylation by MAP Kinases In Vitro and In Vivo.

PubMed

Han, Xiaomin; Li, Guojing; Zhang, Shuqun

2017-01-01

Ethylene, a gaseous phytohormone, has profound effects on plant growth, development, and adaptation to the environment. Ethylene-regulated processes begin with the induction of ethylene biosynthesis. There are two key steps in ethylene biosynthesis. The first is the biosynthesis of 1-aminocyclopropane-1-carboxylic acid (ACC) from S-Adenosyl-Methionine (SAM), a common precursor in many metabolic pathways, which is catalyzed by ACC synthase (ACS). The second is the oxidative cleavage of ACC to form ethylene under the action of ACC oxidase (ACO). ACC biosynthesis is the committing and generally the rate-limiting step in ethylene biosynthesis. As a result, characterizing the cellular ACS activity and understanding its regulation are important. In this chapter, we detail the methods used to measure, (1) the enzymatic activity of both recombinant and native ACS proteins, and (2) the phosphorylation of ACS protein by mitogen-activated protein kinases (MAPKs) in vivo and in vitro.

A functional dissociation of conflict processing within anterior cingulate cortex.

PubMed

Kim, Chobok; Kroger, James K; Kim, Jeounghoon

2011-02-01

Goal-directed behavior requires cognitive control to regulate the occurrence of conflict. The dorsal anterior cingulate cortex (dACC) has been suggested in detecting response conflict during various conflict tasks. Recent findings, however, have indicated not only that two distinct subregions of dACC are involved in conflict processing but also that the conflict occurs at both perceptual and response levels. In this study, we sought to examine whether perceptual and response conflicts are functionally dissociated in dACC. Thirteen healthy subjects performed a version of the Stroop task during functional magnetic resonance imaging (fMRI) scanning. We identified a functional dissociation of the caudal dACC (cdACC) and the rostral dACC (rdACC) in their responses to different sources of conflict. The cdACC was selectively engaged in perceptual conflict whereas the rdACC was more active in response conflict. Further, the dorsolateral prefrontal cortex (DLPFC) was coactivated not with cdACC but with rdACC. We suggest that cdACC plays an important role in regulative processing of perceptual conflict whereas rdACC is involved in detecting response conflict. Copyright © 2010 Wiley-Liss, Inc.

Surgical management and clinical prognosis of adrenocortical carcinoma.

PubMed

Dong, Dexin; Li, Hanzhong; Yan, Weigang; Ji, Zhigang; Mao, Quanzong

2012-01-01

To study the relationship between surgical management and prognosis of adrenocortical carcinoma (ACC) in order to guide the surgical management of ACC. Clinical data of 45 cases of ACC treated in our hospital were retrospectively analyzed. The 45 cases included 3 cases in stage I, 12 cases in stage II, 7 cases in stage III, and 23 cases in stage IV. 17 cases underwent complete excision, 14 cases underwent palliative excision, 8 cases had non-operative treatment and 6 cases gave up treatment. All patients were followed up from 2 to 141 months. The average survival time of 31 patients with surgery was 32.46 months, and the average survival time of 14 patients without surgery was 4.75 months. There were statistically significant differences between the two groups (p < 0.01). There were no statistically significant differences between the two groups in survival time in stage III and stage IV (p > 0.05). Surgery is considered to be the only method to cure ACC. For ACC in stage I and II, tumor resection is the most effective treatment, and second surgical operation is recommended for local recurrence. For ACC in stage III, extensive surgical operation is recommended, and for ACC in stage IV, surgical operation has no effect on the prognosis. Copyright © 2012 S. Karger AG, Basel.

Anti-tumorigenic effect of nano formulated peptide pACC1 by diminishing de novo lipogenisis in DMBA induced mammary carcinoma rat model.

PubMed

Kaliaperumal, Jagatheesh; Padarthi, Pavankumar; Elangovan, Namasivayam; Hari, Natarajan

2014-07-01

At present, the majority of established treatments for breast cancer are based on clinical manifestations, some fundamental of molecular and cellular biology of cancer. In recent times, the therapy is moving towards personalized medicines. Nevertheless, both the methodologies have own demerits. In the present study, we proposed a novel idea of targeted therapy with twin pharmacological potential by a peptide pACC1. The peptide was formulated with chitosan and evaluated with DMBA induced mammary carcinoma. Results suggest that the peptide holds great control on tumor cell multiplication, fatty acid synthesis and lactate levels. In addition, peptide also brings normal metabolic signs in glycolytic and glycogenic pathways. Histological studies confirm the dual pharmacological actions. Further, it is also proven that the peptide controls membrane receptor levels of HER2 and EGFR. In conclusion, that the peptide pACC1 could be employed as greater therapeutic adjuvant with currently established drugs without considering the stage of the cancer. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Ethylene biosynthesis by 1-aminocyclopropane-1-carboxylic acid oxidase: a DFT study.

PubMed

Bassan, Arianna; Borowski, Tomasz; Schofield, Christopher J; Siegbahn, Per E M

2006-11-24

The reaction catalyzed by the plant enzyme 1-aminocyclopropane-1-carboxylic acid oxidase (ACCO) was investigated by using hybrid density functional theory. ACCO belongs to the non-heme iron(II) enzyme superfamily and carries out the bicarbonate-dependent two-electron oxidation of its substrate ACC (1-aminocyclopropane-1-carboxylic acid) concomitant with the reduction of dioxygen and oxidation of a reducing agent probably ascorbate. The reaction gives ethylene, CO(2), cyanide and two water molecules. A model including the mononuclear iron complex with ACC in the first coordination sphere was used to study the details of O-O bond cleavage and cyclopropane ring opening. Calculations imply that this unusual and complex reaction is triggered by a hydrogen atom abstraction step generating a radical on the amino nitrogen of ACC. Subsequently, cyclopropane ring opening followed by O-O bond heterolysis leads to a very reactive iron(IV)-oxo intermediate, which decomposes to ethylene and cyanoformate with very low energy barriers. The reaction is assisted by bicarbonate located in the second coordination sphere of the metal.

Evaluation of the Aristotle complexity models in adult patients with congenital heart disease.

PubMed

Hörer, Jürgen; Vogt, Manfred; Wottke, Michael; Cleuziou, Julie; Kasnar-Samprec, Jelena; Lange, Rüdiger; Schreiber, Christian

2013-01-01

The adult congenital heart disease (CHD) population has surpassed the paediatric CHD population. Half of all mortality caused by CHD occurs in adulthood; in some patients, it occurs during surgery. We sought to assess the potential risk factors for adverse outcome after cardiac operations in adults with CHD, and to evaluate the predictive power of the Aristotle score models for hospital mortality. Procedure-dependent and independent factors, as well as the outcome factors of all consecutive patients aged 16 or more who underwent surgery for CHD between 2005 and 2008 at our institution were evaluated according to the European Association for Cardio-Thoracic Surgery Congenital Database nomenclature. An Aristotle basic complexity (ABC) and an Aristotle comprehensive complexity (ACC) score were assigned to each operation. The discriminatory power of the scores was assessed using the area under the receiver operating characteristics (AuROC) curve. During 542 operations, 773 procedures were performed. The early mortality rate was 2.4%, and the early complication rate was 53.7%. Tricuspid valve replacement (P = 0.009), mitral valve replacement (P < 0.001), elevated lung resistances (P = 0.002), hypothyroidism (P = 0.002) and redosternotomy (P = 0.003) emerged as risk factors for 30-day mortality. Tricuspid valve replacement (P < 0.001), tricuspid valvuloplasty (P = 0.006), mitral valve replacement (P = 0.003), shunt implantation (P = 0.009), surgical ablation (P = 0.024), myocardial dysfunction (P = 0.014), elevated lung resistances (P = 0.004), hypothyroidism (P = 0.002) and redosternotomy (P < 0.001) emerged as risk factors for complications. Mean ABC and ACC scores were 6.6 ± 2.3, and 9.0 ± 3.7, respectively. The AuROCs of the ABC and the ACC scores for 30-day mortality were 0.663 (P = 0.044), and 0.755 (P = 0.002), respectively. The AuROCs of the ABC and the ACC scores for complications were 0.634 (P < 0.001), and 0.670 (P < 0.001), respectively. Surgery for adults with CHD can be performed with low early mortality. However, complications are frequent, especially in patients who require repeat operations for atrioventricular valve incompetence. The ACC score may be helpful to estimate the risk of early mortality.

Comparative effectiveness of ACC-deaminase and/or nitrogen-fixing rhizobacteria in promotion of maize (Zea mays L.) growth under lead pollution.

PubMed

Hassan, Waseem; Bano, Rizwana; Bashir, Farhat; David, Julie

2014-09-01

Lead (Pb) pollution is appearing as an alarming threat nowadays. Excessive Pb concentrations in agricultural soils result in minimizing the soil fertility and health which affects the plant growth and leads to decrease in crop production. Plant growth promoting rhizobacteria (PGPR) are beneficial bacteria which can protect the plants against many abiotic stresses, and enhance the growth. The study aimed to identify important rhizobacterial strains by using the 1-aminocyclopropane-1-carboxylate (ACC) enrichment technique and examine their inoculation effects in the growth promotion of maize, under Pb pollution. A pot experiment was conducted and six rhizobacterial isolates were used. Pb was added to 2 kg soil in each pot (with 4 seeds/pot) using Pb(NO3)2 at the rate of 0, 100, 200, 300, and 400 mg kg(-1) Pb with three replications in completely randomized design. Rhizobacterial isolates performed significantly better under all Pb levels, i.e., 100 to 400 Pb mg kg(-1) soil, compared to control. Comparing the efficacy of the rhizobacterial isolates under different Pb levels, rhizobacterial isolates having both ACC-deaminase and nitrogen-fixing activities (AN8 and AN12) showed highest increase in terms of the physical, chemical and enzymatic growth parameters of maize, followed by the rhizobacterial isolates having ACC-deaminase activity only (ACC5 and ACC8), and then the nitrogen-fixing rhizobia (Azotobacter and RN5). However, the AN8 isolate showed maximum efficiency, and highest shoot and root length (14.2 and 6.1 cm), seedling fresh and dry weights (1.91 and 0.14 g), chlorophyll a, b, and carotenoids (24.1, 30.2 and 77.7 μg/l), protein (0.82 mg/g), proline (3.42 μmol/g), glutathione S-transferase, peroxidase and catalase (12.3, 4.2 and 7.2 units/mg protein), while the lowest Pb uptake in the shoot and root (0.83 and 0.48 mg/kg) were observed under this rhizobial isolate at the highest Pb level (i.e., 400 Pb mg kg(-1) soil). The results revealed that PGPR significantly decreases the deleterious effects of Pb pollution and increases the maize growth under all Pb concentrations, i.e., 100-400 Pb mg kg(-1) soil. PGPR chelate the Pb in the soil, and ultimately influence its bioavailability, release and uptake. The PGPR having both ACC-deaminase and nitrogen-fixing abilities are more effective and resistive against Pb pollution than PGPR having either ACC-deaminase or nitrogen-fixing activity alone. The ACC enrichment technique is an efficient approach to select promising PGPR.

High-molecular-weight fibronectin synthesized by adenoid cystic carcinoma cells of salivary gland origin.

PubMed

Toyoshima, K; Kimura, S; Cheng, J; Oda, Y; Mori, K J; Saku, T

1999-03-01

To understand the morphogenesis of characteristic cribriform structures and the frequent invasion of salivary adenoid cystic carcinomas (ACC) along such basement membrane-rich structures as peripheral nerves, we have isolated fibronectin (FN) from the culture media of ACC3 cells established from a parotid ACC and characterized its glycosylation and alternative splicing status. FN isolated from ACC3 cells (ACC-FN) showed a molecular mass of 315 kDa in SDS-PAGE and was less heterogeneous and larger than plasma FN (pFN) or FNs from other cell sources. Differential enzymatic treatments of immunoprecipitated ACC-FN with neuraminidase, peptide-N-glycosidase F and endo-alpha-N-acetylgalactosaminidase revealed that ACC-FN was composed of a polypeptide chain of 270 kDa, with 10 kDa each of N-linked and O-linked oligosaccharide chains. Reverse transcription polymerase chain reaction (RT-PCR), in-situ hybridization, and immunofluorescence studies showed that most ACC-FNs contained ED-A, ED-B and IIICS regions in the molecules. This alternative splicing status of ACC-FN seemed to contribute to its less heterogeneous and larger molecular form. Cell attachment assay demonstrated that ACC-FN was more potent than pFN in adhesion of ACC3 cells. The results indicated that ACC-FN may function as a substrate for attachment of ACC3 cells, or that ACC3 cells trap and retain ACC-FN in their pericellular space. This isoform of FN may play an important role in the mode of invasion of ACC and the formation of stromal pseudocysts in the characteristic cribriform structure of ACC.

Neural representation of cost-benefit selections in rat anterior cingulate cortex in self-paced decision making.

PubMed

Wang, Shuai; Shi, Yi; Li, Bao-Ming

2017-03-01

The anterior cingulate cortex (ACC) is crucial for decision making which involves the processing of cost-benefit information. Our previous study has shown that ACC is essential for self-paced decision making. However, it is unclear how ACC neurons represent cost-benefit selections during the decision-making process. In the present study, we trained rats on the same "Do More Get More" (DMGM) task as in our previous work. In each trial, the animals stand upright and perform a sustained nosepoke of their own will to earn a water reward, with the amount of reward positively correlated to the duration of the nosepoke (i.e., longer nosepokes earn larger rewards). We then recorded ACC neuronal activity on well-trained rats while they were performing the DMGM task. Our results show that (1) approximately 3/5 ACC neurons (296/496, 59.7%) exhibited changes in firing frequency that were temporally locked with the main events of the DMGM task; (2) about 1/5 ACC neurons (101/496, 20.4%) or 1/3 of the event-modulated neurons (101/296, 34.1%) showed differential firing rate changes for different cost-benefit selections; and (3) many ACC neurons exhibited linear encoding of the cost-benefit selections in the DMGM task events. These results suggest that ACC neurons are engaged in encoding cost-benefit information, thus represent the selections in self-paced decision making. Copyright © 2016 Elsevier Inc. All rights reserved.

Analytical performance issues: comparison of ATP bioluminescence and aerobic bacterial count for evaluating surface cleanliness in an Italian hospital.

PubMed

Amodio, Emanuele; Cannova, Lucia; Villafrate, Maria Rosaria; Merendino, Anna Maria; Aprea, Luigi; Calamusa, Giuseppe

2014-01-01

Contaminated hospital surfaces have been demonstrated to be an important environmental reservoir of microorganisms that can increase the risk of nosocomial infection in exposed patients. As a consequence, cleaning and disinfecting hospital environments play an important role among strategies for preventing healthcare-associated colonization and infections. The aim of the present study was to evaluate whether adenosine triphosphate (ATP) presence, measured by bioluminescence methods, can predict microbiological contamination of hospital surfaces. The study was carried out between September and December 2012 at the University Hospital "P. Giaccone" of Palermo. A total of 193 randomly selected surfaces (tables, lockers, furnishings) were sampled and analyzed in order to assess ATP levels (expressed as relative light units or RLU) and aerobic colony count (ACC) or presence of S. aureus. ACC had median values of 1.85 cfu/cm(2)(interquartile range = 4.16) whereas ATP median was 44.6 RLU/cm(2)(interquartile range = 92.3). Overall, 85 (44.0%) surfaces exceeded the established microbial benchmark: 73 (37.8%) exceeded the 2.5 cfu/cm(2)ACC standard, 5 (2.6%) surfaces were positive for S. aureus and 7 (3.6%) showed both the presence of S. aureus and an ACC of more than 2.5 cfu/cm(2). ACC and bioluminescence showed significant differences in the different surface sites (p < 0.001). A significant correlation was found between ACC and RLU values (p-value < 0.001; R(2)= 0.29) and increasing RLU values were significantly associated with a higher risk of failing the benchmark (p < 0.001). Our data suggest that bioluminescence could help in measuring hygienic quality of hospital surfaces using a quick and sensitive test that can be an useful proxy of microbial contamination; however, further analysis will be necessary to assess the cost-efficacy of this methodology before requiring incorporation in hospital procedures.

Deficiencies in acetyl-CoA carboxylase and fatty acid synthase 1 differentially affect eggshell formation and blood meal digestion in Aedes aegypti.

PubMed

Alabaster, Amy; Isoe, Jun; Zhou, Guoli; Lee, Ada; Murphy, Ashleigh; Day, W Anthony; Miesfeld, Roger L

2011-12-01

To better understand the mechanism of de novo lipid biosynthesis in blood fed Aedes aegypti mosquitoes, we quantitated acetyl-CoA carboxylase (ACC) and fatty acid synthase 1 (FAS1) transcript levels in blood fed mosquitoes, and used RNAi methods to generate ACC and FAS1 deficient mosquitoes. Using the ketogenic amino acid (14)C-leucine as a metabolic precursor of (14)C-acetyl-CoA, we found that (14)C-triacylglycerol and (14)C-phospholipid levels were significantly reduced in both ACC and FAS1 deficient mosquitoes, confirming that ACC and FAS1 are required for de novo lipid biosynthesis after blood feeding. Surprisingly however, we also found that ACC deficient mosquitoes, but not FAS1 deficient mosquitoes, produced defective oocytes, which lacked an intact eggshell and gave rise to inviable eggs. This severe phenotype was restricted to the 1st gonotrophic cycle, suggesting that the eggshell defect was due to ACC deficiencies in the follicular epithelial cells, which are replaced after each gonotrophic cycle. Consistent with lower amounts of de novo lipid biosynthesis, both ACC and FAS1 deficient mosquitoes produced significantly fewer eggs than control mosquitoes in both the 1st and 2nd gonotrophic cycles. Lastly, FAS1 deficient mosquitoes, but not ACC deficient mosquitoes, showed delayed blood meal digestion, suggesting that a feedback control mechanism may coordinate rates of fat body lipid biosynthesis and midgut digestion during feeding. We propose that decreased ACC and FAS1 enzyme levels lead to reduced lipid biosynthesis and lower fecundity, whereas altered levels of the regulatory metabolites acetyl-CoA and malonyl-CoA account for the observed defects in eggshell formation and blood meal digestion, respectively. Copyright © 2011 Elsevier Ltd. All rights reserved.

Deficiencies in acetyl-CoA carboxylase and fatty acid synthase 1 differentially affect eggshell formation and blood meal digestion in Aedes aegypti

PubMed Central

Alabaster, Amy; Isoe, Jun; Zhou, Guoli; Lee, Ada; Murphy, Ashleigh; Day, W. Anthony; Miesfeld, Roger L.

2011-01-01

To better understand the mechanism of de novo lipid biosynthesis in blood fed Ae. aegypti mosquitoes, we quantitated acetyl-CoA carboxylase (ACC) and fatty acid synthase 1 (FAS1) transcript levels in blood fed mosquitoes, and used RNAi methods to generate ACC and FAS1 deficient mosquitoes. Using the ketogenic amino acid 14C-leucine as a metabolic precursor of 14C-acetyl-CoA, we found that 14C-triacylglycerol and 14C-phospholipid levels were significantly reduced in both ACC and FAS1 deficient mosquitoes, confirming that ACC and FAS1 are required for de novo lipid biosynthesis after blood feeding. Surprisingly however, we also found that ACC deficient mosquitoes, but not FAS1 deficient mosquitoes, produced defective oocytes, which lacked an intact eggshell and gave rise to inviable eggs. This severe phenotype was restricted to the 1st gonotrophic cycle, suggesting that the eggshell defect was due to ACC deficiencies in the follicular epithelial cells, which are replaced after each gonotrophic cycle. Consistent with lower amounts of de novo lipid biosynthesis, both ACC and FAS1 deficient mosquitoes produced significantly fewer eggs than control mosquitoes in both the 1st and 2nd gonotrophic cycles. Lastly, FAS1 deficient mosquitoes, but not ACC deficient mosquitoes, showed delayed blood meal digestion, suggesting that a feedback control mechanism may coordinate rates of fat body lipid biosynthesis and midgut digestion during feeding. We propose that decreased ACC and FAS1 enzyme levels lead to reduced lipid biosynthesis and lower fecundity, whereas altered levels of the regulatory metabolites acetyl-CoA and malonyl-CoA account for the observed defects in eggshell formation and blood meal digestion, respectively. PMID:21971482

Diffuse Staining for Activated NOTCH1 Correlates With NOTCH1 Mutation Status and Is Associated With Worse Outcome in Adenoid Cystic Carcinoma.

PubMed

Sajed, Dipti P; Faquin, William C; Carey, Chris; Severson, Eric A; H Afrogheh, Amir; A Johnson, Carl; Blacklow, Stephen C; Chau, Nicole G; Lin, Derrick T; Krane, Jeffrey F; Jo, Vickie Y; Garcia, Joaquín J; Sholl, Lynette M; Aster, Jon C

2017-11-01

NOTCH1 is frequently mutated in adenoid cystic carcinoma (ACC). To test the idea that immunohistochemical (IHC) staining can identify ACCs with NOTCH1 mutations, we performed IHC for activated NOTCH1 (NICD1) in 197 cases diagnosed as ACC from 173 patients. NICD1 staining was positive in 194 cases (98%) in 2 major patterns: subset positivity, which correlated with tubular/cribriform histology; and diffuse positivity, which correlated with a solid histology. To determine the relationship between NICD1 staining and NOTCH1 mutational status, targeted exome sequencing data were obtained on 14 diffusely NICD1-positive ACC specimens from 11 patients and 15 subset NICD1-positive ACC specimens from 15 patients. This revealed NOTCH1 gain-of-function mutations in 11 of 14 diffusely NICD1-positive ACC specimens, whereas all subset-positive tumors had wild-type NOTCH1 alleles. Notably, tumors with diffuse NICD1 positivity were associated with significantly worse outcomes (P=0.003). To determine whether NOTCH1 activation is unique among tumors included in the differential diagnosis with ACC, we performed NICD1 IHC on a cohort of diverse salivary gland and head and neck tumors. High fractions of each of these tumor types were positive for NICD1 in a subset of cells, particularly in basaloid squamous cell carcinomas; however, sequencing of basaloid squamous cell carcinomas failed to identify NOTCH1 mutations. These findings indicate that diffuse NICD1 positivity in ACC correlates with solid growth pattern, the presence of NOTCH1 gain-of-function mutations, and unfavorable outcome, and suggest that staining for NICD1 can be helpful in distinguishing ACC with solid growth patterns from other salivary gland and head and neck tumors.

Objective measurement of subjective tinnitus using the acoustic change complex.

PubMed

Han, Ji-Hye; Won, Joong Yeon; Hong, Sung Kwang; Kim, Ja Hee; Kim, Eun Soo; Kim, Hyung-Jong; Lee, Hyo-Jeong

2017-01-01

At present, there is no objective method for diagnosing subjective sensorineural tinnitus. Recently, the acoustic change complex (ACC) has been used to evaluate neural detection of sounds. Thus, the present study aimed to examine whether the ACC can reflect cortical detection and discrimination of sounds matched with tinnitus frequencies. We hypothesized that the ACC to change stimuli matched with tinnitus frequencies would be decreased in tinnitus patients because the tinnitus interferes with the perception of acoustic changes. To test the hypothesis, 96 ears of normal-hearing (NH) tinnitus patients and controls were tested. Among the tinnitus patients, 33 ears with a tinnitus frequency of 8 kHz constituted the tinnitus group, and the remaining 63 ears with no experience of tinnitus were allocated to the control group. For the 4 kHz non-tinnitus matched frequency, a subset of tinnitus (n = 17) and NH (n = 47) subjects was tested. The acoustic stimuli were pure tones with a total duration of 500 ms consisting of a 1 kHz tone in the first 250 ms and a second tone of either 8 kHz or 4 kHz in the latter 250 ms. The normalized amplitude of the ACC (naACC) was calculated separately for the amplitude of the N1'-P2' complex evoked by an 8 kHz or 4 kHz change stimulus and for the amplitude of the N1-P2 complex elicited by the initial 1 kHz background stimulus. Our results showed that the naACC to an 8 kHz stimulus in the tinnitus group was significantly smaller than those to 4 kHz and 8 kHz in normal controls. Additionally, in the tinnitus group, the naACC to 4 kHz was greater compared to 8 kHz. The receiver operating characteristic (ROC) curve analysis conducted for naACC to 8 kHz at UCL revealed a fair degree of diagnostic efficacy. Overall, our results indicated that the ACC to a change stimulus matched with the tinnitus frequency can provide an objective measure of frequency-specific tinnitus.

Objective measurement of subjective tinnitus using the acoustic change complex

PubMed Central

Han, Ji-Hye; Won, Joong Yeon; Hong, Sung Kwang; Kim, Ja Hee; Kim, Eun Soo; Kim, Hyung-Jong

2017-01-01

At present, there is no objective method for diagnosing subjective sensorineural tinnitus. Recently, the acoustic change complex (ACC) has been used to evaluate neural detection of sounds. Thus, the present study aimed to examine whether the ACC can reflect cortical detection and discrimination of sounds matched with tinnitus frequencies. We hypothesized that the ACC to change stimuli matched with tinnitus frequencies would be decreased in tinnitus patients because the tinnitus interferes with the perception of acoustic changes. To test the hypothesis, 96 ears of normal-hearing (NH) tinnitus patients and controls were tested. Among the tinnitus patients, 33 ears with a tinnitus frequency of 8 kHz constituted the tinnitus group, and the remaining 63 ears with no experience of tinnitus were allocated to the control group. For the 4 kHz non-tinnitus matched frequency, a subset of tinnitus (n = 17) and NH (n = 47) subjects was tested. The acoustic stimuli were pure tones with a total duration of 500 ms consisting of a 1 kHz tone in the first 250 ms and a second tone of either 8 kHz or 4 kHz in the latter 250 ms. The normalized amplitude of the ACC (naACC) was calculated separately for the amplitude of the N1’-P2’ complex evoked by an 8 kHz or 4 kHz change stimulus and for the amplitude of the N1-P2 complex elicited by the initial 1 kHz background stimulus. Our results showed that the naACC to an 8 kHz stimulus in the tinnitus group was significantly smaller than those to 4 kHz and 8 kHz in normal controls. Additionally, in the tinnitus group, the naACC to 4 kHz was greater compared to 8 kHz. The receiver operating characteristic (ROC) curve analysis conducted for naACC to 8 kHz at UCL revealed a fair degree of diagnostic efficacy. Overall, our results indicated that the ACC to a change stimulus matched with the tinnitus frequency can provide an objective measure of frequency-specific tinnitus. PMID:29176873

The transformation of amorphous calcium carbonate, ACC, to crystalline phases as function of time and temperature.

NASA Astrophysics Data System (ADS)

Gies, Hermann; Happel, Marian; Niedermayr, Andrea; Immenhauser, Adrian

2017-04-01

We present results from a structural study of the transformation of freeze dried amorphous calcium carbonate, ACC, in crystalline material using pair distribution function analysis, PDF analysis, of X-ray powder diffraction data, XPD data. PDF analysis allows for the analysis of local order of structural subunit in the range between molecular unit (1. and 2. coordination sphere) and long range periodicity as in crystalline materials. ACC was precipitated from aqueous solutions at 298 K and 278 K using different amounts of Mg cations as stabilizer. The samples were immediately separated from the solution and freeze dried. For the transformation study, the samples were heated and analysed using XPD until they were crystallized. The radial distribution obtained from the XPD data were compared to simulated radial distributions of the calcium carbonate polymorphs and their hydrated phases. An ACC precipitated from a solution with Ca:Mg:CO3 = 1:5:4 at 298 K (ration in mmol, pH = 8.2) and freeze dried right after isolation from the solution revealed a close resemblance with ikaite in its local order. Another ACC with Ca:Mg:CO3 = 1:10:1.4 (T = 298, pH = 8.7) showed distinctly different local order resembling monohydrocalcite. Both ACC, however, still had considerable amounts of water dominating the Ca-coordination sphere. During the transformation to calcite, the structural changes in the sample concerned the hydrate water coordinating Ca which was removed and replaced by the carbonate oxygens. The study shows that ACC obtained from different starting solutions show specific local order. Freeze drying leads to solid ACC powder which still contain considerable amounts of hydrate water. Structural subunits are distinct in ACC and different from the crystalline phase. The study supplements recent reports presented by Konrad et al., Purgstaller et al., and Tobler et al.. F. Konrad et al., Cryst. Growth Des. 16, 6310-6317(2016) B. Purgstaller et al., Geochimica et Cosmochimica Acta 174, 180-195(2016) DJ. Tobler et al., Cryst. Growth Des. 16, 4500-4508(2016)

Biosynthesis of Ethylene from Methionine in Aminoethoxyvinylglycine-Resistant Avocado Tissue

PubMed Central

Baker, James E.; Anderson, James D.; Adams, Douglas O.; Apelbaum, Akiva; Lieberman, Morris

1982-01-01

This study was conducted to determine if aminoethoxyvinylglycine (AVG) insensitivity in avocado (Persea americana Mill., Lula, Haas, and Bacon) tissue was due to an alternate pathway of ethylene biosynthesis from methionine. AVG, at 0.1 millimolar, had little or no inhibitory effect on either total ethylene production or [14C] ethylene production from [14C]methionine in avocado tissue at various stages of ripening. However, aminoxyacetic acid (AOA), which inhibits 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (the AVG-sensitive enzyme of ethylene biosynthesis), inhibited ethylene production in avocado tissue. Total ethylene production was stimulated, and [14C]ethylene production from [14C]methionine was lowered by treating avocado tissue with 1 millimolar ACC. An inhibitor of methionine adenosyltransferase (EC 2.5.1.6), l-2-amino-4-hexynoic acid (AHA), at 1.5 millimolar, effectively inhibited [14C]ethylene production from [14C]methionine in avocado tissue but had no effect on total ethylene production during a 2-hour incubation. Rates of [14C]AVG uptake by avocado and apple (Malus domestica Borkh., Golden Delicious) tissues were similar, and [14C]AVG was the only radioactive compound in alcohol-soluble fractions of the tissues. Hence, AVG-insensitivity in avocado tissue does not appear to be due to lack of uptake or to metabolism of AVG by avocado tissue. ACC synthase activity in extracts of avocado tissue was strongly inhibited (about 60%) by 10 micromolar AVG. Insensitivity of ethylene production in avocado tissue to AVG may be due to inaccessibility of ACC synthase to AVG. AVG-resistance in the avocado system is, therefore, different from that of early climacteric apple tissue, in which AVG-insensitivity of total ethylene production appears to be due to a high level of endogenous ACC relative to its rate of conversion to ethylene. However, the sensitivity of the avocado system to AOA and AHA, dilution of labeled ethylene production by ACC, and stimulation of total ethylene production by ACC provide evidence for the methionine → SAM → ACC → ethylene pathway in avocado and do not suggest the operation of an alternate pathway. PMID:16662192

Is axillary surgery beneficial for patients with adenoid cystic carcinoma of the breast?

PubMed

Welsh, Jessemae L; Keeney, Michael G; Hoskin, Tanya L; Glazebrook, Katrina N; Boughey, Judy C; Shah, Sejal S; Hieken, Tina J

2017-11-01

Adenoid cystic carcinoma (ACC) is a rare, typically triple-negative, breast cancer reported to have a favorable prognosis and low rate of nodal metastasis. No consensus guidelines exist for axillary staging and treatment. We identified all patients with ACC evaluated at our institution from January 1994 to August 2016. Patient, tumor, and treatment variables were abstracted and analyzed. We identified 20 pure ACCs (0.13% of all invasive breast cancers) with size range 0.2-4.8 cm, in 19 women, median age 59 years. Preoperative axillary ultrasound was normal in 10/13 women and suspicious in 3/13 who had a subsequent negative lymph node fine needle aspiration (FNA). Fifteen patients (75%) had sentinel lymph node surgery and were pathologically node-negative, while the remaining five had no axillary surgery. With 3.6 years median follow-up (range 0.2-38.6 years), three patients experienced an in-breast recurrence at 2, 16, and 17 years, respectively, while none recurred in regional nodes. We observed no cases of nodal metastasis in 20 consecutive cases of ACC of the breast. Preoperative axillary ultrasound with FNA of suspicious nodes accurately predicted pathologic nodal stage. These data suggest axillary surgery might be omitted safely in patients with pure ACC and a clinically negative axilla. © 2017 Wiley Periodicals, Inc.

Accumulation and Transport of 1-Aminocyclopropane-1-Carboxylic Acid (ACC) in Plants: Current Status, Considerations for Future Research and Agronomic Applications

PubMed Central

Vanderstraeten, Lisa; Van Der Straeten, Dominique

2017-01-01

1-aminocyclopropane-1-carboxylic acid (ACC) is a non-protein amino acid acting as the direct precursor of ethylene, a plant hormone regulating a wide variety of vegetative and developmental processes. ACC is the central molecule of ethylene biosynthesis. The rate of ACC formation differs in response to developmental, hormonal and environmental cues. ACC can be conjugated to three derivatives, metabolized in planta or by rhizobacteria using ACC deaminase, and is transported throughout the plant over short and long distances, remotely leading to ethylene responses. This review highlights some recent advances related to ACC. These include the regulation of ACC synthesis, conjugation and deamination, evidence for a role of ACC as an ethylene-independent signal, short and long range ACC transport, and the identification of a first ACC transporter. Although unraveling the complex mechanism of ACC transport is in its infancy, new questions emerge together with the identification of a first transporter. In the light of the future quest for additional ACC transporters, this review presents perspectives of the novel findings and includes considerations for future research toward applications in agronomy. PMID:28174583

Accumulation and Transport of 1-Aminocyclopropane-1-Carboxylic Acid (ACC) in Plants: Current Status, Considerations for Future Research and Agronomic Applications.

PubMed

Vanderstraeten, Lisa; Van Der Straeten, Dominique

2017-01-01

1-aminocyclopropane-1-carboxylic acid (ACC) is a non-protein amino acid acting as the direct precursor of ethylene, a plant hormone regulating a wide variety of vegetative and developmental processes. ACC is the central molecule of ethylene biosynthesis. The rate of ACC formation differs in response to developmental, hormonal and environmental cues. ACC can be conjugated to three derivatives, metabolized in planta or by rhizobacteria using ACC deaminase, and is transported throughout the plant over short and long distances, remotely leading to ethylene responses. This review highlights some recent advances related to ACC. These include the regulation of ACC synthesis, conjugation and deamination, evidence for a role of ACC as an ethylene-independent signal, short and long range ACC transport, and the identification of a first ACC transporter. Although unraveling the complex mechanism of ACC transport is in its infancy, new questions emerge together with the identification of a first transporter. In the light of the future quest for additional ACC transporters, this review presents perspectives of the novel findings and includes considerations for future research toward applications in agronomy.

Adoption of the 2013 American College of Cardiology/American Heart Association Cholesterol Management Guideline in Cardiology Practices Nationwide

PubMed Central

Pokharel, Yashashwi; Tang, Fengming; Jones, Philip G.; Nambi, Vijay; Bittner, Vera A.; Hira, Ravi S.; Nasir, Khurram; Chan, Paul S.; Maddox, Thomas M.; Oetgen, William J.; Heidenreich, Paul A.; Borden, William B.; Spertus, John A.; Petersen, Laura A.; Ballantyne, Christie M.

2017-01-01

Importance The 2013 American College of Cardiology/American Heart Association (ACC/AHA) Cholesterol Management Guideline recommends moderate-intensity to high-intensity statin therapy in eligible patients. Objective To examine adoption of the 2013 ACC/AHA guideline in US cardiology practices. Design, Setting, and Participants Among 161 cardiology practices, trends in the use of moderate-intensity to high-intensity statin and nonstatin lipid-lowering therapy (LLT) were analyzed before (September 1, 2012, to November 1, 2013) and after (February 1, 2014, to April 1, 2015) publication of the 2013 ACC/AHA guideline among 4 mutually exclusive risk groups within the ACC Practice Innovation and Clinical Excellence Registry. Interrupted time series analysis was used to evaluate for differences in trend in use of moderate-intensity to high-intensity statin and nonstatin LLT use in hierarchical logistic regression models. Participants were a population-based sample of 1 105 356 preguideline patients (2 431 192 patient encounters) and 1 116 472 postguideline patients (2 377 219 patient encounters). Approximately 97% of patients had atherosclerotic cardiovascular disease (ASCVD). Exposures Moderate-intensity to high-intensity statin and nonstatin LLT use before and after publication of the 2013 ACC/AHA guideline. Main Outcomes and Measures Time trend in the use of moderate-intensity to high-intensity statin and nonstatin LLT. Results In the study cohort, the mean (SD) age was 69.6 (12.1) years among 1 105 356 patients (40.2% female) before publication of the guideline and 70.0 (11.9) years among 1 116 472 patients (39.8% female) after publication of the guideline. Although there was a trend toward increasing use of moderate-intensity to high-intensity statins overall and in the ASCVD cohort, such a trend was already present before publication of the guideline. No significant difference in trend in the use of moderate-intensity to high-intensity statins was observed in other groups. The use of moderate-intensity to high-intensity statin therapy was 62.1% (before publication of the guideline) and 66.6% (after publication of the guideline) in the overall cohort, 62.7% (before publication) and 67.0% (after publication) in the ASCVD cohort, 50.6% (before publication) and 52.3% (after publication) in the cohort with elevated low-density lipoprotein cholesterol levels (ie, ≥190 mg/dL), 52.4% (before publication) and 55.2% (after publication) in the diabetes cohort, and 41.9% (before publication) and 46.9% (after publication) in the remaining group with 10-year ASCVD risk of 7.5% or higher. In hierarchical logistic regression models, there was a significant increase in the use of moderate-intensity to high-intensity statins in the overall cohort (4.8%) and in the ASCVD cohort (4.3%) (P < .01 for slope for both). There was no significant change for other risk cohorts. Nonstatin LLT use remained unchanged in the preguideline and postguideline periods in the hierarchical logistic regression models for all of the risk groups. Conclusions and Relevance Adoption of the 2013 ACC/AHA Cholesterol Management Guideline in cardiology practices was modest. Timely interventions are needed to improve guideline-concordant practice to reduce the burden of ASCVD. PMID:28249067

Cadmium-induced ethylene production and responses in Arabidopsis thaliana rely on ACS2 and ACS6 gene expression

PubMed Central

2014-01-01

Background Anthropogenic activities cause metal pollution worldwide. Plants can absorb and accumulate these metals through their root system, inducing stress as a result of excess metal concentrations inside the plant. Ethylene is a regulator of multiple plant processes, and is affected by many biotic and abiotic stresses. Increased ethylene levels have been observed after exposure to excess metals but it remains unclear how the increased ethylene levels are achieved at the molecular level. In this study, the effects of cadmium (Cd) exposure on the production of ethylene and its precursor 1-aminocyclopropane-1-carboxylic acid (ACC), and on the expression of the ACC Synthase (ACS) and ACC Oxidase (ACO) multigene families were investigated in Arabidopsis thaliana. Results Increased ethylene release after Cd exposure was directly measurable in a system using rockwool-cultivated plants; enhanced levels of the ethylene precursor ACC together with higher mRNA levels of ethylene responsive genes: ACO2, ETR2 and ERF1 also indicated increased ethylene production in hydroponic culture. Regarding underlying mechanisms, it was found that the transcript levels of ACO2 and ACO4, the most abundantly expressed members of the ACO multigene family, were increased upon Cd exposure. ACC synthesis is the rate-limiting step in ethylene biosynthesis, and transcript levels of both ACS2 and ACS6 showed the highest increase and became the most abundant isoforms after Cd exposure, suggesting their importance in the Cd-induced increase of ethylene production. Conclusions Cadmium induced the biosynthesis of ACC and ethylene in Arabidopsis thaliana plants mainly via the increased expression of ACS2 and ACS6. This was confirmed in the acs2-1acs6-1 double knockout mutants, which showed a decreased ethylene production, positively affecting leaf biomass and resulting in a delayed induction of ethylene responsive gene expressions without significant differences in Cd contents between wild-type and mutant plants. PMID:25082369

Alterations in anterior cingulate cortex myoinositol and aggression in veterans with suicidal behavior: A proton magnetic resonance spectroscopy study.

PubMed

Sheth, Chandni; Prescot, Andrew; Bueler, Elliott; DiMuzio, Jennifer; Legarreta, Margaret; Renshaw, Perry F; Yurgelun-Todd, Deborah; McGlade, Erin

2018-06-30

Studies investigating the neurochemical changes that correspond with suicidal behavior (SB) have not yielded conclusive results. Suicide correlates such as aggression have been used to explore risk factors for SB. Yet the neurobiological basis for the association between aggression and SB is unclear. Aggression and SB are both prevalent in veterans relative to civilian populations. The current study evaluated the relationship between brain chemistry in the anterior (ACC) and the posterior cingulate cortex (POC), as well as the relationship between aggression and SB in a veteran population using proton magnetic resonance spectroscopy ( 1 H-MRS). Single-voxel MRS data at 3 Tesla (T) were acquired from the ACC and POC voxels using a 2-dimensional J-resolved point spectroscopy sequence and quantified using the ProFit algorithm. Participants also completed a structured diagnostic interview and a clinical battery. Our results showed that the myoinositol (mI)/H2O ratio in the ACC and POC was significantly higher in veterans who reported SB when compared to veterans who did not. The two groups did not differ significantly with regard to other metabolites. Second, verbal aggression and SB measures positively correlated with mI/H2O in the ACC. Finally, verbal aggression mediated the relationship between mI/H2O in the ACC and SB. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

PubMed

Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

2011-01-01

The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

Glutamate and GABA contributions to medial prefrontal cortical activity to emotion: implications for mood disorders.

PubMed

Stan, Ana D; Schirda, Claudiu V; Bertocci, Michele A; Bebko, Genna M; Kronhaus, Dina M; Aslam, Haris A; LaBarbara, Eduard J; Tanase, Costin; Lockovich, Jeanette C; Pollock, Myrna H; Stiffler, Richelle S; Phillips, Mary L

2014-09-30

The dorsomedial prefrontal cortex (MdPFC) and anterior cingulate cortices (ACC) play a critical role in implicit emotion regulation; however the understanding of the specific neurotransmitters that mediate such role is lacking. In this study, we examined relationships between MdPFC concentrations of two neurotransmitters, glutamate and γ-amino butyric acid (GABA), and BOLD activity in ACC during performance of an implicit facial emotion-processing task. Twenty healthy volunteers, aged 20-35 years, were scanned while performing an implicit facial emotion-processing task, whereby presented facial expressions changed from neutral to one of the four emotions: happy, anger, fear, or sad. Glutamate concentrations were measured before and after the emotion-processing task in right MdPFC using magnetic resonance spectroscopy (MRS). GABA concentrations were measured in bilateral MdPFC after the emotion-processing task. Multiple regression models were run to determine the relative contribution of glutamate and GABA concentration, age, and gender to BOLD signal in ACC to each of the four emotions. Multiple regression analyses revealed a significant negative correlation between MdPFC GABA concentration and BOLD signal in subgenual ACC (p<0.05, corrected) to sad versus shape contrast. For the anger versus shape contrast, there was a significant negative correlation between age and BOLD signal in pregenual ACC (p<0.05, corrected) and a positive correlation between MdPFC glutamate concentration (pre-task) and BOLD signal in pregenual ACC (p<0.05, corrected). Our findings are the first to provide insight into relationships between MdPFC neurotransmitter concentrations and ACC BOLD signal, and could further understanding of molecular mechanisms underlying emotion processing in healthy and mood-disordered individuals. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Growth rate regulation of Escherichia coli acetyl coenzyme A carboxylase, which catalyzes the first committed step of lipid biosynthesis.

PubMed Central

Li, S J; Cronan, J E

1993-01-01

Acetyl coenzyme A (CoA) carboxylase catalyzes the synthesis of malonyl-CoA, the first intermediate of fatty acid synthesis. The Escherichia coli enzyme is encoded by four subunits located at three different positions on the E. coli chromosome. The accBC genes lie in a small operon at min 72, whereas accA and accD are located at min 4.3 and 50, respectively. We examined the expression of the genes that encode the E. coli acetyl-CoA carboxylase subunits (accA, accBC, and accD) under a variety of growth conditions by quantitative Northern (RNA) blot analysis. We found a direct correlation between the levels of transcription of the acc genes and the rate of cellular growth. Consistent results were also obtained upon nutritional upshift and downshift experiments and upon dilution of stationary-phase cultures into fresh media. We also determined the 5' end of the accA and accD mRNAs by primer extension and did transcriptional fusion analysis of the previously reported accBC promoter. Several interesting features were found in the promoter regions of these genes, including a bent DNA sequence and an open reading frame within the unusually long leader mRNA of the accBC operon, potential stem-loop structures in the accA and accD mRNA leader regions, and a stretch of GC-rich sequences followed by AT-rich sequences common to all three promoters. In addition, both accA and accD are located in complex gene clusters. For example, the accA promoter was localized within the upstream polC gene (which encodes the DNA polymerase III catalytic subunit), suggesting that additional regulatory mechanisms exist. Images PMID:7678242

Role of Endocrine Gland-Derived Vascular Endothelial Growth Factor (EG-VEGF) and Its Receptors in Adrenocortical Tumors.

PubMed

Heck, Dorothee; Wortmann, Sebastian; Kraus, Luitgard; Ronchi, Cristina L; Sinnott, Richard O; Fassnacht, Martin; Sbiera, Silviu

2015-12-01

Angiogenesis is essential for tumor growth and metastasis. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor predominantly expressed in steroidogenic organs like the adrenal gland, ovary, testes, and placenta. EG-VEGF has antiapoptotic, mitogenic, and chemoattractive properties mediated via the two G protein-coupled receptors prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2). We investigated the expression of EG-VEGF and its receptors in a large number of normal adrenal glands (NAG), adrenocortical adenomas (ACA), and carcinomas (ACC) using real-time PCR (NAG, n = 12; ACA, n = 24; and ACC, n = 30) and immunohistochemistry (NAG, n = 9; ACA, n = 23; and ACC, n = 163) and evaluated its impact on patients' survival. EG-VEGF, PKR1, and PKR2 mRNA and protein are expressed in NAG and the vast majority of ACA and ACC samples. The mean EG-VEGF mRNA expression was significantly lower in ACC (606.5 ± 77.1 copies) compared to NAG (4,043 ± 1,111) and cortisol-producing adenomas (CPA) (4,433 ± 2,378) (p < 0.01 and p < 0.05, respectively). However, cytoplasmic and nuclear EG-VEGF protein expression was either significantly higher or similar in ACC (H score 2.4 ± 0.05, p < 0.05 and 1.7 ± 0.08, n.s., respectively) compared to NAG (1.8 ± 0.14 and 1.7 ± 0.2). Nuclear protein expression of either EG-VEGF or PKR1 or both is predictive for a higher mortality compared to patients without nuclear expression (hazard ratio (HR) = 5.15; 95% confidence interval (CI) = 1.24-21.36, n = 100, p = 0.02 independent of age, sex, and tumor stage). These findings suggest that EG-VEGF and its receptor PKR1 might play a role in the pathogenesis of adrenocortical tumors and could serve as prognostic markers for this rare malignant disease.

Management of adrenal cancer: a 2013 update.

PubMed

Terzolo, M; Daffara, F; Ardito, A; Zaggia, B; Basile, V; Ferrari, L; Berruti, A

2014-03-01

Adrenocortical carcinoma (ACC) is a devastating tumor for either patients or their families because of short life expectancy and severe impact on quality of life. Due to the rarity of ACC, with a reported annual incidence of 0.5-2 cases per million population, progress in the development of treatment options beyond surgery has been limited. Up to now, no personalized approach of ACC therapy has emerged, apart from plasma level-guided mitotane therapy, and no simple targetable molecular event has been identified from preclinical studies. Complete surgical removal of ACC is the only potentially curative approach and has the most important impact on patient’s prognosis. Despite the limits of the available evidence, adjuvant mitotane therapy is currently recommended in many expert centers whenever the patients present an elevated risk of recurrence. The management of patients with recurrent and metastatic disease is challenging and the prognosis is often poor. Mitotane monotherapy is indicated in the management of patients with a low tumor burden and/or more indolent disease while patients whose disease show an aggressive behavior need cytotoxic chemotherapy. The treatment of patients with advanced ACC may include loco-regional approaches such as surgery and radiofrequency ablation in addition to systemic therapies. The present review provides an updated overview of the management of ACC patients following surgery and of the management of ACC patients with advanced disease.

Rostral anterior cingulate cortex volume correlates with depressed mood in normal healthy children

PubMed Central

Boes, Aaron D.; McCormick, Laurie M.; Coryell, William H.; Nopoulos, Peg

2008-01-01

BACKGROUND The rostral anterior cingulate cortex (rACC) has been implicated as a structural neural correlate of familial major depressive disorder, raising the possibility that the structure of this region may act as a biologic marker of depression vulnerability. The aim of the current study was to determine whether children and adolescents with depressive symptoms have lower rACC volume relative to those without symptoms and examine how a positive family history of depression affects this relationship. METHODS 112 normal healthy children (59 boys, 53 girls), age 7–17, without a current diagnosis or history of depression or other psychiatric illness, were recruited from the community. Mood symptoms were collected using the Pediatric Behavior Scale, a parent- and teacher-reported questionnaire. Volumetric measures of the rACC were generated using structural MRI. The relationship of depressive symptoms and rACC volume was examined. RESULTS 1) The rACC volume was significantly lower in boys with subclinical depressive symptoms compared to boys with no depressive symptoms, particularly on the left side (14.6% reduction; F = 8.90, p = .005). 2) In comparing the correlation of depressive symptoms and rACC volume in boys with a positive family history of depression to those with no family history there was a more robust negative correlation in subjects with a positive family history. 3) In girls there was not a significant association of depressive symptoms and rACC volume. CONCLUSIONS These findings lend further support to the notion that rACC structure may act as a biologic marker of vulnerability or trait-marker of depression. PMID:17916329

Millennial-scale ocean current intensity changes off southernmost Chile and implications for Drake Passage throughflow

NASA Astrophysics Data System (ADS)

Lamy, F.; Arz, H. W.; Kilian, R.; Baeza Urrea, O.; Caniupan, M.; Kissel, C.; Lange, C.

2012-04-01

The Antarctic Circumpolar Current (ACC) plays an essential role in the thermohaline circulation and global climate. Today a large volume of ACC water passes through the Drake Passage, a major geographic constrain for the circumpolar flow. Satellite tracked surface drifters have shown that Subantarctic Surface water of the ACC is transported northeastward across the Southeast Pacific from ~53°S/100°W towards the Chilean coast at ~40°S/75°W where surface waters bifurcate and flow northward into the Peru Chile Current (PCC) finally reaching the Eastern Tropical Pacific, and southwards into the Cape Horn Current (CHC). The CHC thus transports a significant amount of northern ACC water towards the Drake Passage and reaches surface current velocities of up to 35 cm/s within a narrow belt of ~100-150 km width off the coast. Also at deeper water levels, an accelerated southward flow occurs along the continental slope off southernmost South America that likewise substantially contributes to the Drake Passage throughflow. Here we report on high resolution geochemical and grain-size records from core MD07-3128 (53°S; 1032 m water depth) which has been retrieved from the upper continental slope off the Pacific entrance of the Magellan Strait beneath the CHC. Magnetic grain-sizes and grain-size distributions of the terrigenous fraction reveal large amplitude changes between the Holocene and the last glacial, as well as millennial-scale variability (most pronounced during Marine Isotope Stage). Magnetic grain-sizes, silt/clay ratios, fine sand contents, sortable silt contents, and sortable silt mean grain-sizes are substantially higher during the Holocene suggesting strongly enhanced current activity. The high absolute values imply flow speeds larger than 25 cm/s as currently observed in the CHC surface current. Furthermore, winnowing processes through bottom current activity and changes in the availability of terrigenous material (ice-sheet extension and related supply of silt/clay, efficiency of the fjords in trapping sediment) might have contributed to the observed grain-size variations. Assuming that surface and bottom current strength changes are the major controlling factors, our data suggest a strongly enhanced CHC and deeper flow during the Holocene compared to the mean of the last glacial. During MIS 3, several phases of stronger current flow mostly correlate with warm sea surface temperatures at the site and, within age uncertainties, with millennial-scale warm phases in Antarctic ice cores. Taken together our data can be interpreted in terms of strongly reduced contributions of northern ACC water to the Drake Passage throughflow during the glacial in general and during millennial-scale cold phases in particular. At the same time, advection of northern ACC water into the PCC was probably enhanced. These results are consistent with model runs showing largely reduced volume transport through the Drake Passage during the last glacial maximum and an increasing throughflow during the last deglaciation that might have affected the strengthening of the Atlantic Meridional Overturning Circulation.

The onset of modern-like Atlantic meridional overturning circulation at the Eocene-Oligocene transition: Evidence, causes, and possible implications for global cooling

NASA Astrophysics Data System (ADS)

Abelson, Meir; Erez, Jonathan

2017-06-01

A compilation of benthic δ18O from the whole Atlantic and the Southern Ocean (Atlantic sector) shows two major jumps in the interbasinal gradient of δ18O (Δδ18O) during the Eocene and the Oligocene: one at ˜40 Ma and the second concomitant with the isotopic event of the Eocene-Oligocene transition (EOT), ˜33.7 Ma ago. From previously published circulation models and proxies, we show that the first Δδ18O jump reflects the thermal isolation of Antarctica associated with the proto-Antarctic circumpolar current (ACC). The second marks the onset of interhemispheric northern-sourced circulation cell, similar to the modern Atlantic meridional overturning circulation (AMOC). The onset of AMOC-like circulation slightly preceded (100-300 kyr) the EOT, as we show by the high-resolution profiles of δ18O and δ13C previously published from DSDP/ODP sites in the Southern Ocean and South Atlantic. These events coincide with the onset of antiestuarine circulation between the Nordic seas and the North Atlantic which started around the EOT and may be connected to the deepening of the Greenland-Scotland Ridge. We suggest that while the shallow proto-ACC supplied the energy for deep ocean convection in the Southern Hemisphere, the onset of the interhemispheric northern circulation cell was due to the significant EOT intensification of deepwater formation in the North Atlantic driven by the Nordic antiestuarine circulation. This onset of the interhemispheric northern-sourced circulation cell could have prompted the EOT global cooling.