Understanding the mechanism of catalytic fast pyrolysis by unveiling reactive intermediates in heterogeneous catalysis

NASA Astrophysics Data System (ADS)

Hemberger, Patrick; Custodis, Victoria B. F.; Bodi, Andras; Gerber, Thomas; van Bokhoven, Jeroen A.

2017-06-01

Catalytic fast pyrolysis is a promising way to convert lignin into fine chemicals and fuels, but current approaches lack selectivity and yield unsatisfactory conversion. Understanding the pyrolysis reaction mechanism at the molecular level may help to make this sustainable process more economic. Reactive intermediates are responsible for product branching and hold the key to unveiling these mechanisms, but are notoriously difficult to detect isomer-selectively. Here, we investigate the catalytic pyrolysis of guaiacol, a lignin model compound, using photoelectron photoion coincidence spectroscopy with synchrotron radiation, which allows for isomer-selective detection of reactive intermediates. In combination with ambient pressure pyrolysis, we identify fulvenone as the central reactive intermediate, generated by catalytic demethylation to catechol and subsequent dehydration. The fulvenone ketene is responsible for the phenol formation. This technique may open unique opportunities for isomer-resolved probing in catalysis, and holds the potential for achieving a mechanistic understanding of complex, real-life catalytic processes.

Coincidence measurements following 2p photoionization in Mg

NASA Astrophysics Data System (ADS)

Sokell, E.; Bolognesi, P.; Safgren, S.; Avaldi, L.

2014-04-01

Triple Differential Cross-Section (TDCS) measurements have been made to investigate the 2p pho-toionization of Magnesium. In the experiment the photoelectron and the L3-M1M1 Auger electron have been detected in coincidence at four distinct photon energies from 7 to 40 eV above the 2p threshold. Auger decay is usually treated as a two-step process, where the intermediate single hole-state makes the link between the pho-toionization and decay processes. These measurements allow the investigation of the process as a function of excess energy, and specifically to test the validity of the two-step model as the ionization threshold is approached.

Regulation of EMMPRIN (CD147) on monocyte subsets in patients with symptomatic coronary artery disease.

PubMed

Sturhan, Henrik; Ungern-Sternberg, Saskia N I v; Langer, Harald; Gawaz, Meinrad; Geisler, Tobias; May, Andreas E; Seizer, Peter

2015-06-01

The role of individual monocyte subsets in inflammatory cardiovascular diseases is insufficiently understood. Although the Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) regulates important processes for inflammation such as MMP-release, its expression and regulation on monocyte subsets has not been characterized. In this clinical study, blood was obtained from 80 patients with stable coronary artery disease (CAD), 49 with acute myocardial infarction (AMI) and 34 healthy controls. Monocytes were divided into 3 subsets: CD14(++)CD16(-) (low), CD14(++)CD16(+) (intermediate), CD14(+)CD16(++) (high) according to phenotypic markers analyzed by flow cytometry. Surface expression of EMMPRIN was evaluated and compared with CD36 and CD47 expression. In all patients, EMMPRIN expression was significantly different among monocyte subsets with the highest expression on "classical" CD14(++)CD16(-) monocytes. EMMPRIN was upregulated on all monocyte subsets in patients with AMI as compared to patients with stable CAD. Notably, neither CD47 nor CD36 revealed a significant difference in patients with AMI compared to patients with stable CAD. EMMPRIN could serve as a marker for classical monocytes, which is upregulated in patients with acute myocardial infarction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Design of focused and restrained subsets from extremely large virtual libraries.

PubMed

Jamois, Eric A; Lin, Chien T; Waldman, Marvin

2003-11-01

With the current and ever-growing offering of reagents along with the vast palette of organic reactions, virtual libraries accessible to combinatorial chemists can reach sizes of billions of compounds or more. Extracting practical size subsets for experimentation has remained an essential step in the design of combinatorial libraries. A typical approach to computational library design involves enumeration of structures and properties for the entire virtual library, which may be unpractical for such large libraries. This study describes a new approach termed as on the fly optimization (OTFO) where descriptors are computed as needed within the subset optimization cycle and without intermediate enumeration of structures. Results reported herein highlight the advantages of coupling an ultra-fast descriptor calculation engine to subset optimization capabilities. We also show that enumeration of properties for the entire virtual library may not only be unpractical but also wasteful. Successful design of focused and restrained subsets can be achieved while sampling only a small fraction of the virtual library. We also investigate the stability of the method and compare results obtained from simulated annealing (SA) and genetic algorithms (GA).

Monocyte profile in peripheral blood of gestational diabetes mellitus patients.

PubMed

Angelo, Ana G S; Neves, Carla T C; Lobo, Thalita F; Godoy, Ramon V C; Ono, Érika; Mattar, Rosiane; Daher, Silvia

2018-07-01

Gestational diabetes Mellitus has been considered an inflammatory disease involving different cells and mediators in its development. The role of innate immune cells in GDM physiopathology remains unclear, therefore this study was conducted to assess monocyte profile in GDM patients. This was a case-control study including 20 glucose-tolerant pregnant women (controls) and 18 GDM patients. Flow cytometry was used to assess peripheral blood monocytes subsets (classical, intermediate, non-classical), the expression of TLR4 and CCR2 chemokine receptor (CD192) and cytokines (TNFA, IL6, IL10) secretion by monocytes subsets. In addition, sCD14 serum levels were evaluated by ELISA. We observed increased percentage of CD14 + cells, decreased frequency of intermediate monocytes (CD14 + CD16 + ), and lower percentage of circulating monocytes (classical, intermediate and non-classical) that express TLR4 in the diabetic group compared to controls. Soluble CD14 + serum levels were higher in GDM patients compared to controls. There were no differences in the expression of the CCR2 chemokine receptor and cytokines (TNFA, IL6 and IL10) secretion between the studied groups. Our results demonstrated that GDM patients present impaired monocyte profile in the peripheral blood, suggesting that these cells are involved in GDM physiopathology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Farnesol-Detecting Olfactory Neurons in Drosophila

PubMed Central

Ronderos, David S.; Lin, Chun-Chieh; Potter, Christopher J.

2014-01-01

We set out to deorphanize a subset of putative Drosophila odorant receptors expressed in trichoid sensilla using a transgenic in vivo misexpression approach. We identified farnesol as a potent and specific activator for the orphan odorant receptor Or83c. Farnesol is an intermediate in juvenile hormone biosynthesis, but is also produced by ripe citrus fruit peels. Here, we show that farnesol stimulates robust activation of Or83c-expressing olfactory neurons, even at high dilutions. The CD36 homolog Snmp1 is required for normal farnesol response kinetics. The neurons expressing Or83c are found in a subset of poorly characterized intermediate sensilla. We show that these neurons mediate attraction behavior to low concentrations of farnesol and that Or83c receptor mutants are defective for this behavior. Or83c neurons innervate the DC3 glomerulus in the antennal lobe and projection neurons relaying information from this glomerulus to higher brain centers target a region of the lateral horn previously implicated in pheromone perception. Our findings identify a sensitive, narrowly tuned receptor that mediates attraction behavior to farnesol and demonstrates an effective approach to deorphanizing odorant receptors expressed in neurons located in intermediate and trichoid sensilla that may not function in the classical “empty basiconic neuron” system. PMID:24623773

Tabletop Femtosecond VUV Photoionization and PEPICO Detection of Microreactor Pyrolysis Products.

PubMed

Couch, David E; Buckingham, Grant T; Baraban, Joshua H; Porterfield, Jessica P; Wooldridge, Laura A; Ellison, G Barney; Kapteyn, Henry C; Murnane, Margaret M; Peters, William K

2017-07-20

We report the combination of tabletop vacuum ultraviolet photoionization with photoion-photoelectron coincidence spectroscopy for sensitive, isomer-specific detection of nascent products from a pyrolysis microreactor. Results on several molecules demonstrate two essential capabilities that are very straightforward to implement: the ability to differentiate isomers and the ability to distinguish thermal products from dissociative ionization. Here, vacuum ultraviolet light is derived from a commercial tabletop femtosecond laser system, allowing data to be collected at 10 kHz; this high repetition rate is critical for coincidence techniques. The photoion-photoelectron coincidence spectrometer uses the momentum of the ion to identify dissociative ionization events and coincidence techniques to provide a photoelectron spectrum specific to each mass, which is used to distinguish different isomers. We have used this spectrometer to detect the pyrolysis products that result from the thermal cracking of acetaldehyde, cyclohexene, and 2-butanol. The photoion-photoelectron spectrometer can detect and identify organic radicals and reactive intermediates that result from pyrolysis. Direct comparison of laboratory and synchrotron data illustrates the advantages and potential of this approach.

Tabletop Femtosecond VUV Photoionization and PEPICO Detection of Microreactor Pyrolysis Products

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

Couch, David E.; Buckingham, Grant T.; Baraban, Joshua H.

Here, we report the combination of tabletop vacuum ultraviolet photoionization with photoion--photoelectron coincidence spectroscopy for sensitive, isomer-specific detection of nascent products from a pyrolysis microreactor. Results on several molecules demonstrate two essential capabilities that are very straightforward to implement: the ability to differentiate isomers, and to distinguish thermal products from dissociative ionization. We derive vacuum ultraviolet light is from a commercial tabletop femtosecond laser system, allowing data to be collected at 10 kHz; this high repetition rate is critical for coincidence techniques. The photoion—photoelectron coincidence spectrometer uses the momentum of the ion to identify dissociative ionization events, and coincidence techniquesmore » to provide a photoelectron spectrum specific to each mass, which is used to distinguish different isomers. We also have used this spectrometer to detect the pyrolysis products that result from the thermal cracking of acetaldehyde, cyclohexene, and 2-butanol. The photoion—photoelectron spectrometer can detect and identify organic radicals and reactive intermediates that result from pyrolysis. Direct comparison of laboratory and synchrotron data illustrate the advantages and potential of this approach.« less

Tabletop Femtosecond VUV Photoionization and PEPICO Detection of Microreactor Pyrolysis Products

DOE PAGES

Couch, David E.; Buckingham, Grant T.; Baraban, Joshua H.; ...

2017-06-29

Here, we report the combination of tabletop vacuum ultraviolet photoionization with photoion--photoelectron coincidence spectroscopy for sensitive, isomer-specific detection of nascent products from a pyrolysis microreactor. Results on several molecules demonstrate two essential capabilities that are very straightforward to implement: the ability to differentiate isomers, and to distinguish thermal products from dissociative ionization. We derive vacuum ultraviolet light is from a commercial tabletop femtosecond laser system, allowing data to be collected at 10 kHz; this high repetition rate is critical for coincidence techniques. The photoion—photoelectron coincidence spectrometer uses the momentum of the ion to identify dissociative ionization events, and coincidence techniquesmore » to provide a photoelectron spectrum specific to each mass, which is used to distinguish different isomers. We also have used this spectrometer to detect the pyrolysis products that result from the thermal cracking of acetaldehyde, cyclohexene, and 2-butanol. The photoion—photoelectron spectrometer can detect and identify organic radicals and reactive intermediates that result from pyrolysis. Direct comparison of laboratory and synchrotron data illustrate the advantages and potential of this approach.« less

The continuum of monocyte phenotypes: Experimental evidence and prognostic utility in assessing cardiovascular risk.

PubMed

Cignarella, Andrea; Tedesco, Serena; Cappellari, Roberta; Fadini, Gian Paolo

2018-03-30

The monocyte-macrophage cell lineage represents a major player in innate immunity, and is involved in many physiologic and pathologic conditions. Particularly, monocyte-macrophages play a very important role in atherosclerosis and cardiovascular disease. Monocyte heterogeneity is well recognized but the biologic and clinical meaning of the various monocyte subtypes is not entirely understood. Traditionally, monocytes can be divided in classical, intermediate, and nonclassical based on expression of the surface antigens CD14 and CD16. While macrophage diversity is now well recognized to organize as a continuum, monocyte subsets have long been considered as separated entities. However, mounting evidence obtained by tracking the ontology of human monocytes help clarifying that monocytes mature from classical to nonclassical ones, through an intermediate phenotype. This concept is therefore best depicted as a continuum, whereas the subdivision into discrete CD14/CD16 subsets appears an oversimplification. In this review, we discuss the evidence supporting the existence of a monocyte continuum along with the technical challenges of monocyte characterization. In particular, we describe the advantage of considering monocytes along a continuous distribution for the evaluation of cardiovascular risk. We make the point that small transition along the monocyte continuum better reflects cardiovascular risk than a simplified analysis of discrete monocyte subsets. Recognizing the monocyte continuum can be helpful to model other pathophysiologic conditions where these cells are involved. ©2018 Society for Leukocyte Biology.

Deformation quantizations with separation of variables on a Kähler manifold

NASA Astrophysics Data System (ADS)

Karabegov, Alexander V.

1996-10-01

We give a simple geometric description of all formal differentiable deformation quantizations on a Kähler manifold M such that for each open subset U⊂ M ⋆-multiplication from the left by a holomorphic function and from the right by an antiholomorphic function on U coincides with the pointwise multiplication by these functions. We show that these quantizations are in 1-1 correspondence with the formal deformations of the original Kähler metrics on M.

Man-portable Vector Time Domain EMI Sensor and Discrimination Processing

DTIC Science & Technology

2012-04-16

points of each winding are coincident. Each receiver coil is wound helically on a set of 10 grooves etched on the surface of the cube; 36- gauge wire...subset of the data, and inject various levels of noise into the position of the MPV in order to gauge the robustness of the discrimination results...as possible. The quantity φ also provides a metric to gauge goodness of fit, being essentially an average percent error: Benjamin Barrowes, Kevin

Understanding the mechanism of catalytic fast pyrolysis by unveiling reactive intermediates in heterogeneous catalysis

PubMed Central

Hemberger, Patrick; Custodis, Victoria B. F.; Bodi, Andras; Gerber, Thomas; van Bokhoven, Jeroen A.

2017-01-01

Catalytic fast pyrolysis is a promising way to convert lignin into fine chemicals and fuels, but current approaches lack selectivity and yield unsatisfactory conversion. Understanding the pyrolysis reaction mechanism at the molecular level may help to make this sustainable process more economic. Reactive intermediates are responsible for product branching and hold the key to unveiling these mechanisms, but are notoriously difficult to detect isomer-selectively. Here, we investigate the catalytic pyrolysis of guaiacol, a lignin model compound, using photoelectron photoion coincidence spectroscopy with synchrotron radiation, which allows for isomer-selective detection of reactive intermediates. In combination with ambient pressure pyrolysis, we identify fulvenone as the central reactive intermediate, generated by catalytic demethylation to catechol and subsequent dehydration. The fulvenone ketene is responsible for the phenol formation. This technique may open unique opportunities for isomer-resolved probing in catalysis, and holds the potential for achieving a mechanistic understanding of complex, real-life catalytic processes. PMID:28660882

Analysis of PD-1 expression in the monocyte subsets from non-septic and septic preterm neonates

PubMed Central

Lenart, Marzena; Rutkowska-Zapała, Magdalena; Stec, Małgorzata; Durlak, Wojciech; Grudzień, Andrzej; Krzeczkowska, Agnieszka; Mól, Nina; Pilch, Marta; Siedlar, Maciej; Kwinta, Przemko

2017-01-01

Programmed death-1 (PD-1) receptor system represents a part of recently reported immunoregulatory pathway. PD-1 is an immune checkpoint molecule, which plays an important role in downregulating the immune system proinflammatory activity. Until recently, PD-1 expression was not established on immune cells of the preterm infants. The study objectives were to confirm expression of the PD-1 receptors on the monocytes isolated from very low birth weight newborns (VLBW), and to analyze their expression during the first week of life and late-onset sepsis. Peripheral blood mononuclear cells were isolated from 76 VLBW patients without early-onset sepsis on their 5th day of life (DOL). PD-1 expression was determined on the monocyte subsets (classical, intermediate, non-classical) by flow cytometry. In case of late-onset sepsis (LOS), the same analysis was performed. Our results demonstrated that on the 5th DOL, PD-1 receptors were present in all the monocyte subsets. Children, whose mothers had received antenatal steroids, presented higher absolute numbers of non-classical monocytes with PD-1 expression. Infants born extremely preterm who later developed LOS, initially showed a lower percentage of PD-1 receptor-positive intermediate monocytes in comparison to neonates born very preterm. During LOS, we observed a rise in the percentage of classical monocytes with PD-1 expression. In case of septic shock or fatal outcome, there was a higher percentage and absolute count of intermediate monocytes with PD-1 expression in comparison to children without these complications. In conclusion, monocytes from VLBW children express PD-1 receptors. Antenatal steroid administration seems to induce PD-1 receptor expression in the non-classical monocytes. PD-1 might play a role in immunosuppressive phase of sepsis in the prematurely born children with septic shock and fatal outcome. PMID:29049359

Differential Interaction of Platelet-Derived Extracellular Vesicles with Leukocyte Subsets in Human Whole Blood.

PubMed

Weiss, René; Gröger, Marion; Rauscher, Sabine; Fendl, Birgit; Eichhorn, Tanja; Fischer, Michael B; Spittler, Andreas; Weber, Viktoria

2018-04-26

Secretion and exchange of biomolecules via extracellular vesicles (EVs) are crucial mechanisms in intercellular communication, and the roles of EVs in infection, inflammation, or thrombosis have been increasingly recognized. EVs have emerged as central players in immune regulation and can enhance or suppress the immune response, depending on the state of donor and recipient cells. We investigated the interaction of blood cell-derived EVs with leukocyte subpopulations (monocytes and their subsets, granulocytes, B cells, T cells, and NK cells) directly in whole blood using a combination of flow cytometry, imaging flow cytometry, cell sorting, and high resolution confocal microscopy. Platelet-derived EVs constituted the majority of circulating EVs and were preferentially associated with granulocytes and monocytes, while they scarcely interacted with lymphocytes. Further flow cytometric differentiation of monocyte subsets provided clear indications for a preferential association of platelet-derived EVs with intermediate (CD14 ++ CD16 + ) monocytes in whole blood.

Monocyte Phenotype and Polyfunctionality Are Associated With Elevated Soluble Inflammatory Markers, Cytomegalovirus Infection, and Functional and Cognitive Decline in Elderly Adults

PubMed Central

de Pablo-Bernal, Rebeca Sara; Cañizares, Julio; Rosado, Isaac; Galvá, María Isabel; Alvarez-Ríos, Ana Isabel; Carrillo-Vico, Antonio; Ferrando-Martínez, Sara; Muñoz-Fernández, María Ángeles; Rafii-El-Idrissi Benhnia, Mohammed; Pacheco, Yolanda María; Ramos, Raquel; Leal, Manuel; Ruiz-Mateos, Ezequiel

2016-01-01

Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (α), IL1-beta (β), IL-6, IL-8, TNF-α, and IL-10 of elderly adults (median 83 [67–90] years old; n = 20) compared with young controls (median 35 [27–40] years old; n = 20). Ex vivo, the elderly adults showed a higher percentage of classical monocytes that expressed intracellular IL1-α (p = .001), IL1-β (p = .001), IL-6 (p = .002), and IL-8 (p = .007). Similar results were obtained both for the intermediate and nonclassical subsets and in vitro. Polyfunctionality was higher in the elderly adults. The functionality ex vivo was strongly associated with soluble inflammatory markers. The activation phenotype was independently associated with the anti-cytomegalovirus IgG levels and with functional and cognitive decline. These data demonstrate that monocytes are key cell candidates for the source of the high soluble inflammatory levels. Our findings suggest that cytomegalovirus infection might be a driving force in the activation of monocytes and is associated with the functional and cognitive decline. PMID:26286603

Paleohydrologic regimes in the southwestern Great Basin, 0-3.2 my ago, compared with other long records of "gobal" climate

USGS Publications Warehouse

Smith, G.I.

1984-01-01

Nine distinct paleohydrologic regimes in the southwestern Great Basin over the last 3.2 my are recorded by the lacustrine deposits in KM-3, a 930-m core from Searles Lake, California. These are characterized as being "wet," "intermediate," or "dry" (like today). Excepting the present incomplete regime, each lasted 0.12 to 0.76 my. Major regime changes 0.01, 0.13, 0.6, and 2.5 my ago appear to coincide with recognized changes in global ice-sheet histories as represented by 18O and other records from marine sediments, but comparable changes 0.3, 1.0, 1.3, and 2.0 my ago do not appear to coincide closely with comparable perturbations in ice-sheet histories. However, all regime boundaries (during the last 1.75 my) coincide closely in time with changes in sea-surface temperatures in the tropical Atlantic, and many coincide with other deep-sea and continental paleoclimatic boundaries.The average duration of these paleohydrologic regimes was about 0.4 my (standard deviation, 0.2 my or less, depending on assumptions), and it is suggested that the regime boundaries reflect times of change in global(?) sea-surface temperatures, possibly controlled in part by the Earth's 413,000-yr orbital eccentricity cycle. During the wettest and driest regimes in the Searles Lake area, lake levels were not sufficiently affected by the 23,000-, to 42,000-, or 100,000-yr climate cycles related to high-latitude ice-sheet fluctuations to produce changes in the lacustrine sediment character. During intermediate regimes, however, when lacustrine sedimentation in this area was more sensitive to climate, the sediments, in KM-3, record lake fluctuations with average frequencies near those of the ice sheets. This seems to indicate that the high-latitude ice-sheet fluctuations caused local climatic perturbations but did not dominate the hydrologic component of climate in this area. Other lacustrine deposits in the southwestern Great Basin of California and Nevada have ages comparable in part to those of the wet to intermediate regimes indicated by KM-3, and they may all be products of finite periods when lake expansion, alluvial fan growth, increased spring discharge, and fluvial deposition were promoted in this area by widespread wet climates. Glacier expansion in the Sierra Nevada may also have been primarily an expression of, and in phase with, these wet regimes. ?? 1984.

Internal friction and mode relaxation in a simple chain model.

PubMed

Fugmann, S; Sokolov, I M

2009-12-21

We consider the equilibrium relaxation properties of the end-to-end distance and of the principal components in a one-dimensional polymer chain model with nonlinear interaction between the beads. While for the single-well potentials these properties are similar to the ones of a Rouse chain, for the double-well interaction potentials, modeling internal friction, they differ vastly from the ones of the harmonic chain at intermediate times and intermediate temperatures. This minimal description within a one-dimensional model mimics the relaxation properties found in much more complex polymer systems. Thus, the relaxation time of the end-to-end distance may grow by orders of magnitude at intermediate temperatures. The principal components (whose directions are shown to coincide with the normal modes of the harmonic chain, whatever interaction potential is assumed) not only display larger relaxation times but also subdiffusive scaling.

Reformulation of time-convolutionless mode-coupling theory near the glass transition

NASA Astrophysics Data System (ADS)

Tokuyama, Michio

2017-10-01

The time-convolutionless mode-coupling theory (TMCT) recently proposed is reformulated under the condition that one of two approximations, which have been used to formulate the original TMCT in addition to the MCT approximations done on a derivation of nonlinear memory function in terms of the intermediate-scattering function, is not employed because it causes unphysical results for intermediate times. The improved TMCT equation is then derived consistently under another approximation. It is first checked that the ergodic to non-ergodic transition obtained by a new equation is exactly the same as that obtained by an old one because the long-time dynamics of both equations coincides with each other. However, it is emphasized that a difference between them appears in the intermediate-time dynamics of physical quantities. Such a difference is explored numerically in the dynamics of a non-Gaussian parameter by employing the Percus-Yevick static structure factor to calculate the nonlinear memory function.

Electrochemical Detection of Transient Cobalt Hydride Intermediates of Electrocatalytic Hydrogen Production

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

Wiedner, Eric S.; Bullock, R. Morris

2016-07-06

We report the use of variable scan rate cyclic voltammetry to detect transient CoIIIH and CoIIH intermediates of electrocatalytic H2 production by CoII(dmgBF2)2(CH3CN)2 and [CoII(PtBu2NPh2)(CH3CN)3]2+. In both cases, reduction of the CoIIIH intermediate was observed to coincide with the CoII/I couple, and the resulting CoIIH intermediate is protonated by acid to afford H2. Our studies indicate that in electrocatalytic H2 production, protonation of CoIIH is rate-limiting for CoII(dmgBF2)2(CH3CN)2, and protonation of CoI is rate-limiting for [CoII(PtBu2NPh2)(CH3CN)3]2+. This research was supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the U.S. Department of Energy,more » Office of Science, Office of Basic Energy Sciences. Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy.« less

Increase in Peripheral Blood Intermediate Monocytes is Associated with the Development of Recent-Onset Type 1 Diabetes Mellitus in Children.

PubMed

Ren, Xiaoya; Mou, Wenjun; Su, Chang; Chen, Xi; Zhang, Hui; Cao, Bingyan; Li, Xiaoqiao; Wu, Di; Ni, Xin; Gui, Jingang; Gong, Chunxiu

2017-01-01

Monocytes play important roles in antigen presentation and cytokine production to achieve a proper immune response, and are therefore largely implicated in the development and progression of autoimmune diseases. The aim of this study was to analyze the change in the intermediate (CD14+CD16+) monocyte subset in children with recent-onset type 1 diabetes mellitus (T1DM) and its possible association with clinical parameters reflecting islet β-cell dysfunction. Compared with age- and sex-matched healthy controls, intermediate monocytes were expanded in children with T1DM, which was positively associated with hemoglobin A1C and negatively associated with serum insulin and C-peptide. Interestingly, the intermediate monocytes in T1DM patients expressed higher levels of human leukocyte antigen-DR and CD86, suggesting better antigen presentation capability. Further analysis revealed that the frequency of CD45RO+CD4+ memory T cells was increased in the T1DM patients, and the memory T cell content was well correlated with the increase in intermediate monocytes. These results suggest that expanded intermediate monocytes are a predictive factor for the poor residual islet β-cell function in children with recent-onset T1DM.

Echinostoma trivolvis (Digenea: Echinostomatidae) second intermediate host preference matches host suitability.

PubMed

Wojdak, Jeremy M; Clay, Letitia; Moore, Sadé; Williams, Taylore; Belden, Lisa K

2013-02-01

Many trematodes infect a single mollusk species as their first intermediate host, and then infect a variety of second intermediate host species. Determining the factors that shape host specificity is an important step towards understanding trematode infection dynamics. Toward this end, we studied two pond snails (Physa gyrina and Helisoma trivolvis) that can be infected as second intermediate hosts by the trematode Echinostoma trivolvis lineage a (ETa). We performed laboratory preference trials with ETa cercariae in the presence of both snail species and also characterized host suitability by quantifying encystment and excystment success for each host species alone. We tested the prediction that trematodes might preferentially infect species other than their obligate first intermediate host (in this case, H. trivolvis) as second intermediate hosts to avoid potentially greater host mortality associated with residing in first intermediate hosts. In our experiments, ETa had roughly equivalent encystment success in Helisoma and Physa snails, but greater excystment success in Physa, when offered each species in isolation. Also, the presence of the symbiotic oligochaete Chaetogaster limnaei in a subset of Helisoma snails reduced encystment success in those individuals. When both hosts were present, we found dramatically reduced infection prevalence and intensity in Helisoma-ETa cercariae strongly preferred Physa. Thus, the presence of either an alternative host, or a predator of free-living parasites, offered protection for Helisoma snails from E. trivolvis lineage a infection.

Somatic mutation load of estrogen receptor-positive breast tumors predicts overall survival: an analysis of genome sequence data.

PubMed

Haricharan, Svasti; Bainbridge, Matthew N; Scheet, Paul; Brown, Powel H

2014-07-01

Breast cancer is one of the most commonly diagnosed cancers in women. While there are several effective therapies for breast cancer and important single gene prognostic/predictive markers, more than 40,000 women die from this disease every year. The increasing availability of large-scale genomic datasets provides opportunities for identifying factors that influence breast cancer survival in smaller, well-defined subsets. The purpose of this study was to investigate the genomic landscape of various breast cancer subtypes and its potential associations with clinical outcomes. We used statistical analysis of sequence data generated by the Cancer Genome Atlas initiative including somatic mutation load (SML) analysis, Kaplan-Meier survival curves, gene mutational frequency, and mutational enrichment evaluation to study the genomic landscape of breast cancer. We show that ER(+), but not ER(-), tumors with high SML associate with poor overall survival (HR = 2.02). Further, these high mutation load tumors are enriched for coincident mutations in both DNA damage repair and ER signature genes. While it is known that somatic mutations in specific genes affect breast cancer survival, this study is the first to identify that SML may constitute an important global signature for a subset of ER(+) tumors prone to high mortality. Moreover, although somatic mutations in individual DNA damage genes affect clinical outcome, our results indicate that coincident mutations in DNA damage response and signature ER genes may prove more informative for ER(+) breast cancer survival. Next generation sequencing may prove an essential tool for identifying pathways underlying poor outcomes and for tailoring therapeutic strategies.

DNA Helicase HIM-6/BLM Both Promotes MutSγ-Dependent Crossovers and Antagonizes MutSγ-Independent Interhomolog Associations During Caenorhabditis elegans Meiosis

PubMed Central

Schvarzstein, Mara; Pattabiraman, Divya; Libuda, Diana E.; Ramadugu, Ajit; Tam, Angela; Martinez-Perez, Enrique; Roelens, Baptiste; Zawadzki, Karl A.; Yokoo, Rayka; Rosu, Simona; Severson, Aaron F.; Meyer, Barbara J.; Nabeshima, Kentaro; Villeneuve, Anne M.

2014-01-01

Meiotic recombination is initiated by the programmed induction of double-strand DNA breaks (DSBs), lesions that pose a potential threat to the genome. A subset of the DSBs induced during meiotic prophase become designated to be repaired by a pathway that specifically yields interhomolog crossovers (COs), which mature into chiasmata that temporarily connect the homologs to ensure their proper segregation at meiosis I. The remaining DSBs must be repaired by other mechanisms to restore genomic integrity prior to the meiotic divisions. Here we show that HIM-6, the Caenorhabditis elegans ortholog of the RecQ family DNA helicase BLM, functions in both of these processes. We show that him-6 mutants are competent to load the MutSγ complex at multiple potential CO sites, to generate intermediates that fulfill the requirements of monitoring mechanisms that enable meiotic progression, and to accomplish and robustly regulate CO designation. However, recombination events at a subset of CO-designated sites fail to mature into COs and chiasmata, indicating a pro-CO role for HIM-6/BLM that manifests itself late in the CO pathway. Moreover, we find that in addition to promoting COs, HIM-6 plays a role in eliminating and/or preventing the formation of persistent MutSγ-independent associations between homologous chromosomes. We propose that HIM-6/BLM enforces biased outcomes of recombination events to ensure that both (a) CO-designated recombination intermediates are reliably resolved as COs and (b) other recombination intermediates reliably mature into noncrossovers in a timely manner. PMID:25053665

M&A For Lithography Of Sparse Arrays Of Sub-Micrometer Features

DOEpatents

Brueck, Steven R.J.; Chen, Xiaolan; Zaidi, Saleem; Devine, Daniel J.

1998-06-02

Methods and apparatuses are disclosed for the exposure of sparse hole and/or mesa arrays with line:space ratios of 1:3 or greater and sub-micrometer hole and/or mesa diameters in a layer of photosensitive material atop a layered material. Methods disclosed include: double exposure interferometric lithography pairs in which only those areas near the overlapping maxima of each single-period exposure pair receive a clearing exposure dose; double interferometric lithography exposure pairs with additional processing steps to transfer the array from a first single-period interferometric lithography exposure pair into an intermediate mask layer and a second single-period interferometric lithography exposure to further select a subset of the first array of holes; a double exposure of a single period interferometric lithography exposure pair to define a dense array of sub-micrometer holes and an optical lithography exposure in which only those holes near maxima of both exposures receive a clearing exposure dose; combination of a single-period interferometric exposure pair, processing to transfer resulting dense array of sub-micrometer holes into an intermediate etch mask, and an optical lithography exposure to select a subset of initial array to form a sparse array; combination of an optical exposure, transfer of exposure pattern into an intermediate mask layer, and a single-period interferometric lithography exposure pair; three-beam interferometric exposure pairs to form sparse arrays of sub-micrometer holes; five- and four-beam interferometric exposures to form a sparse array of sub-micrometer holes in a single exposure. Apparatuses disclosed include arrangements for the three-beam, five-beam and four-beam interferometric exposures.

Screening the modern girl: intermediality in the adaptation of "Flaming Youth".

PubMed

Ross, Sara

2010-01-01

In the early 1920s, the film industry seized on the furor over the modern girls' demands for sexual liberty and fulfillment inside and outside of marriage to introduce not only new subject matter, but new modes of addressing its diverse audience. Social upheaval in this period coincided with the media industries' movement toward unprecedented speed of adaptation and cooperation, making possible a powerful new intermediality. The film industry used this to generate layered meanings beyond the confines of the film text, encouraging bold viewers to see through the camouflage with which it sought to appease more traditionalist audience members. With Flaming Youth, through a smokescreen of melodramatic conventions and moral lessons, it delivered a strikingly modern conception of sexuality and marriage to the big screen.

Prognosticators and risk grouping in patients with lung metastasis from nasopharyngeal carcinoma: a more accurate and appropriate assessment of prognosis.

PubMed

Cao, Xun; Luo, Rong-Zhen; He, Li-Ru; Li, Yong; Lin, Wen-Qian; Chen, You-Fang; Wen, Zhe-Sheng

2011-08-26

Lung metastases arising from nasopharyngeal carcinomas (NPC) have a relatively favourable prognosis. The purpose of this study was to identify the prognostic factors and to establish a risk grouping in patients with lung metastases from NPC. A total of 198 patients who developed lung metastases from NPC after primary therapy were retrospectively recruited from January 1982 to December 2000. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Actuarial survival rates were plotted against time using the Kaplan-Meier method, and log-rank testing was used to compare the differences between the curves. The median overall survival (OS) period and the lung metastasis survival (LMS) period were 51.5 and 20.9 months, respectively. After univariate and multivariate analyses of the clinical variables, age, T classification, N classification, site of metastases, secondary metastases and disease-free interval (DFI) correlated with OS, whereas age, VCA-IgA titre, number of metastases and secondary metastases were related to LMS. The prognoses of the low- (score 0-1), intermediate- (score 2-3) and high-risk (score 4-8) subsets based on these factors were significantly different. The 3-, 5- and 10-year survival rates of the low-, intermediate- and high-risk subsets, respectively (P < 0.001) were as follows: 77.3%, 60% and 59%; 52.3%, 30% and 27.8%; and 20.5%, 7% and 0%. In this study, clinical variables provided prognostic indicators of survival in NPC patients with lung metastases. Risk subsets would help in a more accurate assessment of a patient's prognosis in the clinical setting and could facilitate the establishment of patient-tailored medical strategies and supports.

Evidence of a Weakly Absorbing Intermediate Mode of Aerosols in AERONET Data from Saharan and Sahelian Sites

NASA Technical Reports Server (NTRS)

Gianelli, Scott M.; Lacis, Andrew A.; Carlson, Barbara E.; Hameed, Sultan

2013-01-01

Accurate retrievals of aerosol size distribution are necessary to estimate aerosols' impact on climate and human health. The inversions of the Aerosol Robotic Network (AERONET) usually retrieve bimodal distributions. However, when the inversion is applied to Saharan and Sahelian dust, an additional mode of intermediate size between the coarse and fine modes is sometimes seen. This mode explains peculiarities in the behavior of the Angstrom exponent, along with the fine mode fraction retrieved using the spectral deconvolution algorithm, observed in a March 2006 dust storm. For this study, 15 AERONET sites in northern Africa and on the Atlantic are examined to determine the frequency and properties of the intermediate mode. The mode is observed most frequently at Ilorin in Nigeria. It is also observed at Capo Verde and multiple sites located within the Sahel but much less frequently at sites in the northern Sahara and the Canary Islands. The presence of the intermediate mode coincides with increases in Angstrom exponent, fine mode fraction, single-scattering albedo, and to a lesser extent percent sphericity. The Angstrom exponent decreases with increasing optical depth at most sites when the intermediate mode is present, but the fine mode fraction does not. Single-scattering albedo does not steadily decrease with fine mode fraction when the intermediate mode is present, as it does in typical mixtures of dust and biomass-burning aerosols. Continued investigation is needed to further define the intermediate mode's properties, determine why it differs from most Saharan dust, and identify its climate and health effects.

Induction of intermediate mesoderm by retinoic acid receptor signaling from differentiating mouse embryonic stem cells.

PubMed

Oeda, Shiho; Hayashi, Yohei; Chan, Techuan; Takasato, Minoru; Aihara, Yuko; Okabayashi, Koji; Ohnuma, Kiyoshi; Asashima, Makoto

2013-01-01

Renal lineages including kidney are derived from intermediate mesoderm, which are differentiated from a subset of caudal undifferentiated mesoderm. The inductive mechanisms of mammalian intermediate mesoderm and renal lineages are still poorly understood. Mouse embryonic stem cells (mESCs) can be a good in vitro model to reconstitute the developmental pathway of renal lineages and to analyze the mechanisms of the sequential differentiation. We examined the effects of Activin A and retinoic acid (RA) on the induction of intermediate mesoderm from mESCs under defined, serum-free, adherent, monolayer culture conditions. We measured the expression level of intermediate mesodermal marker genes and examined the developmental potential of the differentiated cells into kidney using an ex vivo transplantation assay. Adding Activin A followed by RA to mESC cultures induced the expression of marker genes and proteins for intermediate mesoderm, odd-skipped related 1 (Osr1) and Wilm’s Tumor 1 (Wt1). These differentiated cells integrated into laminin-positive tubular cells and Pax2-positive renal cells in cultured embryonic kidney explants. We demonstrated that intermediate mesodermal marker expression was also induced by RA receptor (RAR) agonist, but not by retinoid X receptor (RXR) agonists. Furthermore, the expression of these markers was decreased by RAR antagonists. We directed the differentiation of mESCs into intermediate mesoderm using Activin A and RA and revealed the role of RAR signaling in this differentiation. These methods and findings will improve our understanding of renal lineage development and could contribute to the regenerative medicine of kidney.

DNA helicase HIM-6/BLM both promotes MutSγ-dependent crossovers and antagonizes MutSγ-independent interhomolog associations during caenorhabditis elegans meiosis.

PubMed

Schvarzstein, Mara; Pattabiraman, Divya; Libuda, Diana E; Ramadugu, Ajit; Tam, Angela; Martinez-Perez, Enrique; Roelens, Baptiste; Zawadzki, Karl A; Yokoo, Rayka; Rosu, Simona; Severson, Aaron F; Meyer, Barbara J; Nabeshima, Kentaro; Villeneuve, Anne M

2014-09-01

Meiotic recombination is initiated by the programmed induction of double-strand DNA breaks (DSBs), lesions that pose a potential threat to the genome. A subset of the DSBs induced during meiotic prophase become designated to be repaired by a pathway that specifically yields interhomolog crossovers (COs), which mature into chiasmata that temporarily connect the homologs to ensure their proper segregation at meiosis I. The remaining DSBs must be repaired by other mechanisms to restore genomic integrity prior to the meiotic divisions. Here we show that HIM-6, the Caenorhabditis elegans ortholog of the RecQ family DNA helicase BLM, functions in both of these processes. We show that him-6 mutants are competent to load the MutSγ complex at multiple potential CO sites, to generate intermediates that fulfill the requirements of monitoring mechanisms that enable meiotic progression, and to accomplish and robustly regulate CO designation. However, recombination events at a subset of CO-designated sites fail to mature into COs and chiasmata, indicating a pro-CO role for HIM-6/BLM that manifests itself late in the CO pathway. Moreover, we find that in addition to promoting COs, HIM-6 plays a role in eliminating and/or preventing the formation of persistent MutSγ-independent associations between homologous chromosomes. We propose that HIM-6/BLM enforces biased outcomes of recombination events to ensure that both (a) CO-designated recombination intermediates are reliably resolved as COs and (b) other recombination intermediates reliably mature into noncrossovers in a timely manner. Copyright © 2014 by the Genetics Society of America.

The Connection Between X-ray Binaries and Star Clusters in the Antennae

NASA Astrophysics Data System (ADS)

Rangelov, Blagoy; Chandar, R.; Prestwich, A.

2011-05-01

High Mass X-ray Binaries (HMXBs) are believed to form in massive, compact star clusters. However the correlation between these young binary star systems and properties of their parent clusters are still poorly known. We compare the locations of 82 X-ray binaries detected in the merging Antennae galaxies by Zezas et al. (2006) based on observations taken with the Chandra Space Telescope, with a catalog of optically selected star clusters presented recently by Whitmore et al. (2010) based on observations taken with the Hubble Space Telescope. We find 22 X-ray binaries coincident or nearly coincident with star clusters. The ages of the clusters were estimated by comparing their UBVIHα colors with predictions from stellar evolutionary models. We find that 14 of the 22 coincident sources (64%) are hosted by star clusters with ages of 6 Myr or less. At these very young ages, only stars initially more massive than M ≥ 30 Msun have evolved into compact remnants, almost certainly black holes. Therefore, these 14 sources are likely to be black hole binaries. Five of the XRBs are hosted by young clusters with ages τ 30-50 Myr, while three are hosted by intermediate age clusters with τ 100-300 Myr. We suggest that these older X-ray binaries likely have neutron stars as the compact object. We conclude that precision age-dating of star clusters, which are spatially coincident with XRBs in nearby star forming galaxies, is a powerful method of constraining the nature of the XRBs.

SU-G-IeP4-12: Performance of In-111 Coincident Gamma-Ray Counting: A Monte Carlo Simulation

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

Pahlka, R; Kappadath, S; Mawlawi, O

2016-06-15

Purpose: The decay of In-111 results in a non-isotropic gamma-ray cascade, which is normally imaged using a gamma camera. Creating images with a gamma camera using coincident gamma-rays from In-111 has not been previously studied. Our objective was to explore the feasibility of imaging this cascade as coincidence events and to determine the optimal timing resolution and source activity using Monte Carlo simulations. Methods: GEANT4 was used to simulate the decay of the In-111 nucleus and to model the gamma camera. Each photon emission was assigned a timestamp, and the time delay and angular separation for the second gamma-ray inmore » the cascade was consistent with the known intermediate state half-life of 85ns. The gamma-rays are transported through a model of a Siemens dual head Symbia “S” gamma camera with a 5/8-inch thick crystal and medium energy collimators. A true coincident event was defined as a single 171keV gamma-ray followed by a single 245keV gamma-ray within a specified time window (or vice versa). Several source activities (ranging from 10uCi to 5mCi) with and without incorporation of background counts were then simulated. Each simulation was analyzed using varying time windows to assess random events. The noise equivalent count rate (NECR) was computed based on the number of true and random counts for each combination of activity and time window. No scatter events were assumed since sources were simulated in air. Results: As expected, increasing the timing window increased the total number of observed coincidences albeit at the expense of true coincidences. A timing window range of 200–500ns maximizes the NECR at clinically-used source activities. The background rate did not significantly alter the maximum NECR. Conclusion: This work suggests coincident measurements of In-111 gamma-ray decay can be performed with commercial gamma cameras at clinically-relevant activities. Work is ongoing to assess useful clinical applications.« less

Reassessment of the risk factors for biochemical recurrence in D'Amico intermediate-risk prostate cancer treated using radical prostatectomy.

PubMed

Narita, Shintaro; Mitsuzuka, Koji; Tsuchiya, Norihiko; Koie, Takuya; Kawamura, Sadafumi; Ohyama, Chikara; Tochigi, Tatsuo; Yamaguchi, Takuhiro; Arai, Yoichi; Habuchi, Tomonori

2015-11-01

To assess the risk factors for biochemical recurrence in D'Amico intermediate-risk prostate cancer patients treated using radical prostatectomy. We retrospectively reviewed the medical records of 1268 men with prostate cancer treated using radical prostatectomy without neoadjuvant therapy. The association between various risk factors and biochemical recurrence was then statistically evaluated. The Kaplan-Meier method, log-rank tests and Cox proportional hazards models were used for statistical analysis. In the intermediate-risk group, 96 patients (14.5%) experienced biochemical recurrence during a median follow up of 41 months. In the intermediate-risk group, preoperative prostate-specific antigen level, prostate volume and prostate-specific antigen density were significant preoperative risk factors for biochemical recurrence, whereas other factors including age, primary Gleason 4, clinical stage >T2 and percentage of positive biopsies were not. In multivariate analysis, higher preoperative prostate-specific antigen level and density, and a smaller prostate volume were independent risk factors for biochemical recurrence in the intermediate-risk group. Biochemical recurrence-free survival of patients in the intermediate-risk group with a higher prostate-specific antigen level and density (≥15 ng/mL, ≥0.6 ng/mL/cm(3), respectively), and lower prostate volume (≤10 mL) was comparable with that of high-risk group individuals (P = 0.632, 0.494 and 0.961, respectively). Preoperative prostate-specific antigen, prostate volume and prostate-specific antigen density are significant risk factors for biochemical recurrence in D'Amico intermediate-risk prostate cancer patients treated using radical prostatectomy. Using these variables, a subset of the intermediate-risk patients can be identified as having equivalent outcomes to high-risk patients. © 2015 The Japanese Urological Association.

Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques.

PubMed

Chang, W L William; Gonzalez, Denise F; Kieu, Hung T; Castillo, Luis D; Messaoudi, Ilhem; Shen, Xiaoying; Tomaras, Georgia D; Shacklett, Barbara L; Barry, Peter A; Sparger, Ellen E

2017-01-01

Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV) infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease.

The influence of an arduous military training program on immune function and upper respiratory tract infection incidence.

PubMed

Whitham, Martin; Laing, Stewart J; Dorrington, Melanie; Walters, Robert; Dunklin, Steve; Bland, Duncan; Bilzon, James L J; Walsh, Neil P

2006-08-01

The effects of the first 19 weeks of U.K. Parachute Regiment (PARA) training on upper respiratory tract infection (URTI) incidence and immune function (circulating leukocyte counts, lymphocyte subsets, lipopolysaccharide-stimulated neutrophil degranulation, and salivary immunoglobulin A concentrations) were investigated for 14 PARA recruits and 12 control subjects. No significant differences were reported between groups for the number or duration of URTIs, lymphocyte subsets, or salivary immunoglobulin A concentrations during training. URTI incidence was greater in the PARA group at weeks 2 and 3 (p < 0.05), coinciding with a decrease in circulating leukocyte and lymphocyte counts (p < 0.05). Neutrophil degranulation was similar in the PARA and control groups at weeks 0 and 19. Decreases in saliva flow rate occurred in the PARA group at week 15 and weeks 18 to 20 (p < 0.05). These results show a limited effect of PARA training on URTI incidence and immune function. The progressive decrease in saliva flow rate during PARA training may indicate an ensuing state of hypohydration.

An intermediate level of CD161 expression defines a novel activated, inflammatory, and pathogenic subset of CD8+ T cells involved in multiple sclerosis.

PubMed

Nicol, Bryan; Salou, Marion; Vogel, Isabel; Garcia, Alexandra; Dugast, Emilie; Morille, Jeremy; Kilens, Stéphanie; Charpentier, Eric; Donnart, Audrey; Nedellec, Steven; Jacq-Foucher, Marylène; Le Frère, Fabienne; Wiertlewski, Sandrine; Bourreille, Arnaud; Brouard, Sophie; Michel, Laure; David, Laurent; Gourraud, Pierre-Antoine; Degauque, Nicolas; Nicot, Arnaud B; Berthelot, Laureline; Laplaud, David-Axel

2018-03-01

Several lines of evidence support a key role for CD8 + T cells in central nervous system tissue damage of patients with multiple sclerosis. However, the precise phenotype of the circulating CD8 + T cells that may be recruited from the peripheral blood to invade the CNS remains largely undefined to date. It has been suggested that IL-17 secreting CD8 (Tc17) T cells may be involved, and in humans these cells are characterized by the expression of CD161. We focused our study on a unique and recently described subset of CD8 T cells characterized by an intermediate expression of CD161 as its role in neuroinflammation has not been investigated to date. The frequency, phenotype, and function of CD8 + T cells with an intermediate CD161 expression level were characterized ex-vivo, in vitro, and in situ using RNAseq, RT-PCR, flow cytometry, TCR sequencing, and immunohistofluorescence of cells derived from healthy volunteers (n = 61), MS subjects (n = 90), as well as inflammatory (n = 15) and non-inflammatory controls (n = 6). We report here that CD8 + CD161 int T cells present characteristics of effector cells, up-regulate cell-adhesion molecules and have an increased ability to cross the blood-brain barrier and to secrete IL-17, IFNγ, GM-CSF, and IL-22. We further demonstrate that these cells are recruited and enriched in the CNS of MS subjects where they produce IL-17. In the peripheral blood, RNAseq, RT-PCR, high-throughput TCR repertoire analyses, and flow cytometry confirmed an increased effector and transmigration pattern of these cells in MS patients, with the presence of supernumerary clones compared to healthy controls. Our data demonstrate that intermediate levels of CD161 expression identifies activated and effector CD8 + T cells with pathogenic properties that are recruited to MS lesions. This suggests that CD161 may represent a biomarker and a valid target for the treatment of neuroinflammation. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multiple groups of orientation-selective visual mechanisms underlying rapid orientated-line detection.

PubMed Central

Foster, D H; Westland, S

1998-01-01

Visual search for an edge or line element differing in orientation from a background of other edge or line elements can be performed rapidly and effortlessly. In this study, based on psychophysical measurements with ten human observers, threshold values of the angle between a target and background line elements were obtained as functions of background-element orientation, in brief masked displays. A repeated-loess analysis of the threshold functions suggested the existence of several groups of orientation-selective mechanisms contributing to rapid orientated-line detection; specifically, coarse, intermediate and fine mechanisms with preferred orientations spaced at angles of approximately 90 degrees, 35 degrees, and 10 degrees-25 degrees, respectively. The preferred orientations of coarse and some intermediate mechanisms coincided with the vertical or horizontal of the frontoparallel plane, but the preferred orientations of fine mechanisms varied randomly from observer to observer, possibly reflecting individual variations in neuronal sampling characteristics. PMID:9753784

Expansion of Pathogen-Specific T-Helper 1 and T-Helper 17 Cells in Pulmonary Tuberculosis With Coincident Type 2 Diabetes Mellitus

PubMed Central

Kumar, Nathella Pavan; Sridhar, Rathinam; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.; Nutman, Thomas B.; Babu, Subash

2013-01-01

Background. Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis, although the immunological mechanisms underlying this interaction remain unexplored. The influence of poorly controlled diabetes on pathogen-specific T-helper 1 (Th1) and T-helper 17 (Th17) responses have not been examined. Methods. To identify the role of Th1 and Th17 cells in tuberculosis with coincident DM, we examined mycobacteria-specific immune responses in the whole blood of individuals who had tuberculosis with DM and compared them to those in individuals who had tuberculosis without DM. Results. Tuberculosis coincident with DM is characterized by elevated frequencies of monofunctional and dual-functional CD4+ Th1 cells following Mycobacterium tuberculosis antigen stimulation and elevated frequencies of Th17 subsets at both baseline and following antigen stimulation. This was associated with increased systemic (plasma) levels of both Th1 and Th17 cytokines and decreased baseline frequencies of natural regulatory T cells but not interleukin 10 or transforming growth factor β. Conclusions. Therefore, our data reveal that tuberculosis in persons with DM is characterized by elevated frequencies of Th1 and Th17 cells, indicating that DM is associated with an alteration in the immune response to tuberculosis, leading to a biased induction of Th1- and Th17-mediated cellular responses and likely contributing to increased immune pathology in M. tuberculosis infection. PMID:23715661

A beta-ray spectrometer based on a two-or three silicon detector coincidence telescope

NASA Astrophysics Data System (ADS)

Horowitz, Y. S.; Weizman, Y.; Hirning, C. R.

1996-02-01

This report describes the operation of a beta-ray energy spectrometer based on a silicon detector telescope using two or three elements. The front detector is a planar, totally-depleted, silicon surface barrier detector that is 97 μm thick, the back detector is a room-temperature, lithium compensated, silicon detector that is 5000 μm thick, and the intermediate detector is similar to the front detector but 72 μm thick and intended to be used only in intense photon fields. The three detectors are mounted in a light-tight aluminum housing. The capability of the spectrometer to reject photons is based upon the fact that the incident photon will have a small probability of simultaneously losing detectable energy in two detectors, and an even smaller probability of losing detectable energy in all three detectors. Electrons will, however, almost always record measurable events in either the front two or all three detectors. A coincidence requirement between the detectors thus rejects photon induced events. With a 97 μm thick detector the lower energy coincidence threshold is approximately 110 keV. With an ultra-thin 40 μm thick front detector, and operated at 15°C, the spectrometer is capable of detecting even 60-70 keV electrons with a coincidence efficiency of 60%. The spectrometer has been used to measure beta radiation fields in CANDU reactor working environments, and the spectral information is intended to support dose algorithms for the LiF TLD chips used in the Ontario Hydro dosimetry program.

Gravity and antigravity in a brane world with metastable gravitons

NASA Astrophysics Data System (ADS)

Gregory, R.; Rubakov, V. A.; Sibiryakov, S. M.

2000-09-01

In the framework of a five-dimensional three-brane model with quasi-localized gravitons we evaluate metric perturbations induced on the positive tension brane by matter residing thereon. We find that at intermediate distances, the effective four-dimensional theory coincides, up to small corrections, with General Relativity. This is in accord with Csaki, Erlich and Hollowood and in contrast to Dvali, Gabadadze and Porrati. We show, however, that at ultra-large distances this effective four-dimensional theory becomes dramatically different: conventional tensor gravity changes into scalar anti-gravity.

Wavelength dependent photoelectron circular dichroism of limonene studied by femtosecond multiphoton laser ionization and electron-ion coincidence imaging

NASA Astrophysics Data System (ADS)

Rafiee Fanood, Mohammad M.; Janssen, Maurice H. M.; Powis, Ivan

2016-09-01

Enantiomers of the monoterpene limonene have been investigated by (2 + 1) resonance enhanced multiphoton ionization and photoelectron circular dichroism employing tuneable, circularly polarized femtosecond laser pulses. Electron imaging detection provides 3D momentum measurement while electron-ion coincidence detection can be used to mass-tag individual electrons. Additional filtering, by accepting only parent ion tagged electrons, can be then used to provide discrimination against higher energy dissociative ionization mechanisms where more than three photons are absorbed to better delineate the two photon resonant, one photon ionization pathway. The promotion of different vibrational levels and, tentatively, different electronic ion core configurations in the intermediate Rydberg states can be achieved with different laser excitation wavelengths (420 nm, 412 nm, and 392 nm), in turn producing different state distributions in the resulting cations. Strong chiral asymmetries in the lab frame photoelectron angular distributions are quantified, and a comparison made with a single photon (synchrotron radiation) measurement at an equivalent photon energy.

Eolian sediment responses to late Quaternary climate changes: Temporal and spatial patterns in the Sahara

USGS Publications Warehouse

Swezey, C.

2001-01-01

This paper presents a compilation of eolian-based records of late Quaternary climate changes in the Sahara. Although the data are relatively sparse, when viewed as a whole, they reveal a general pattern of widespread eolian sediment mobilization prior to 11,000 cal. years BP, eolian sediment stabilization from 11,000 to 5000 cal. years BP, and a return to widespread eolian sediment mobilization after 5000 cal. years BP. Furthermore, an eolian-based record from southern Tunisia reveals the existence of millennial-scale changes in eolian sediment behavior. These millennial-scale variations provide examples of eolian sediment responses to climate changes at a scale intermediate between seasonal and orbital ('Milankovitch') changes, and they are also coincident with abrupt atmospheric and oceanic changes. The general synchroneity of the eolian stratigraphic records and their coincidence with various oceanic and atmospheric changes suggest that global forcing mechanisms have influenced late Quaternary eolian sediment behavior in the Sahara. ?? 2001 Elsevier Science B.V.

Smc5/6-Mms21 Prevents and Eliminates Inappropriate Recombination Intermediates in Meiosis

PubMed Central

Xaver, Martin; Huang, Lingzhi; Chen, Doris; Klein, Franz

2013-01-01

Repairing broken chromosomes via joint molecule (JM) intermediates is hazardous and therefore strictly controlled in most organisms. Also in budding yeast meiosis, where production of enough crossovers via JMs is imperative, only a subset of DNA breaks are repaired via JMs, closely regulated by the ZMM pathway. The other breaks are repaired to non-crossovers, avoiding JM formation, through pathways that require the BLM/Sgs1 helicase. “Rogue” JMs that escape the ZMM pathway and BLM/Sgs1 are eliminated before metaphase by resolvases like Mus81-Mms4 to prevent chromosome nondisjunction. Here, we report the requirement of Smc5/6-Mms21 for antagonizing rogue JMs via two mechanisms; destabilizing early intermediates and resolving JMs. Elimination of the Mms21 SUMO E3-ligase domain leads to transient JM accumulation, depending on Mus81-Mms4 for resolution. Absence of Smc6 leads to persistent rogue JMs accumulation, preventing chromatin separation. We propose that the Smc5/6-Mms21 complex antagonizes toxic JMs by coordinating helicases and resolvases at D-Loops and HJs, respectively. PMID:24385936

Investigation of the open-circuit voltage in wide-bandgap InGaP-host InP quantum dot intermediate-band solar cells

NASA Astrophysics Data System (ADS)

Aihara, Taketo; Tayagaki, Takeshi; Nagato, Yuki; Okano, Yoshinobu; Sugaya, Takeyoshi

2018-04-01

To analyze the open-circuit voltage (V oc) in intermediate-band solar cells, we investigated the current-voltage characteristics in wide-bandgap InGaP-based InP quantum dot (QD) solar cells. From the temperature dependence of the current-voltage curves, we show that the V oc in InP QD solar cells increases with decreasing temperature. We use a simple diode model to extract V oc at the zero-temperature limit, V 0, and the temperature coefficient C of the solar cells. Our results show that, while the C of InP QD solar cells is slightly larger than that of the reference InGaP solar cells, V 0 significantly decreases and coincides with the bandgap energy of the InP QDs rather than that of the InGaP host. This V 0 indicates that the V oc reduction in the InP QD solar cells is primarily caused by the breaking of the Fermi energy separation between the QDs and the host semiconductor in intermediate-band solar cells, rather than by enhanced carrier recombination.

Enantioselectivity in Candida antarctica lipase B: A molecular dynamics study

PubMed Central

Raza, Sami; Fransson, Linda; Hult, Karl

2001-01-01

A major problem in predicting the enantioselectivity of an enzyme toward substrate molecules is that even high selectivity toward one substrate enantiomer over the other corresponds to a very small difference in free energy. However, total free energies in enzyme-substrate systems are very large and fluctuate significantly because of general protein motion. Candida antarctica lipase B (CALB), a serine hydrolase, displays enantioselectivity toward secondary alcohols. Here, we present a modeling study where the aim has been to develop a molecular dynamics-based methodology for the prediction of enantioselectivity in CALB. The substrates modeled (seven in total) were 3-methyl-2-butanol with various aliphatic carboxylic acids and also 2-butanol, as well as 3,3-dimethyl-2-butanol with octanoic acid. The tetrahedral reaction intermediate was used as a model of the transition state. Investigative analyses were performed on ensembles of nonminimized structures and focused on the potential energies of a number of subsets within the modeled systems to determine which specific regions are important for the prediction of enantioselectivity. One category of subset was based on atoms that make up the core structural elements of the transition state. We considered that a more favorable energetic conformation of such a subset should relate to a greater likelihood for catalysis to occur, thus reflecting higher selectivity. The results of this study conveyed that the use of this type of subset was viable for the analysis of structural ensembles and yielded good predictions of enantioselectivity. PMID:11266619

Do high energy astrophysical neutrinos trace star formation?

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

Emig, Kimberly; Windhorst, Rogier; Lunardini, Cecilia, E-mail: Kimberly.Emig@asu.edu, E-mail: Cecilia.Lunardini@asu.edu, E-mail: Rogier.Windhorst@asu.edu

2015-12-01

The IceCube Neutrino Observatory has provided the first map of the high energy (∼ 0.01–1 PeV) sky in neutrinos. Since neutrinos propagate undeflected, their arrival direction is an important identifier for sources of high energy particle acceleration. Reconstructed arrival directions are consistent with an extragalactic origin, with possibly a galactic component, of the neutrino flux. We present a statistical analysis of positional coincidences of the IceCube neutrinos with known astrophysical objects from several catalogs. When considering starburst galaxies with the highest flux in gamma-rays and infrared radiation, up to n=8 coincidences are found, representing an excess over the ∼4 predicted formore » the randomized, or ''null'' distribution. The probability that this excess is realized in the null case, the p-value, is p=0.042. This value falls to p=0.003 for a partial subset of gamma-ray-detected starburst galaxies and superbubble regions in the galactic neighborhood. Therefore, it is possible that starburst galaxies, and the typically hundreds of superbubble regions within them, might account for a portion of IceCube neutrinos. The physical plausibility of such correlation is discussed briefly.« less

Quantitation of ten 30S ribosomal assembly intermediates using fluorescence triple correlation spectroscopy

PubMed Central

Ridgeway, William K.; Millar, David P.; Williamson, James R.

2012-01-01

The self-assembly of bacterial 30S ribosomes involves a large number of RNA folding and RNA-protein binding steps. The sequence of steps determines the overall assembly mechanism and the structure of the mechanism has ramifications for the robustness of biogenesis and resilience against kinetic traps. Thermodynamic interdependencies of protein binding inferred from omission-reconstitution experiments are thought to preclude certain assembly pathways and thus enforce ordered assembly, but this concept is at odds with kinetic data suggesting a more parallel assembly landscape. A major challenge is deconvolution of the statistical distribution of intermediates that are populated during assembly at high concentrations approaching in vivo assembly conditions. To specifically resolve the intermediates formed by binding of three ribosomal proteins to the full length 16S rRNA, we introduce Fluorescence Triple-Correlation Spectroscopy (F3CS). F3CS identifies specific ternary complexes by detecting coincident fluctuations in three-color fluorescence data. Triple correlation integrals quantify concentrations and diffusion kinetics of triply labeled species, and F3CS data can be fit alongside auto-correlation and cross-correlation data to quantify the populations of 10 specific ribosome assembly intermediates. The distribution of intermediates generated by binding three ribosomal proteins to the entire native 16S rRNA included significant populations of species that were not previously thought to be thermodynamically accessible, questioning the current interpretation of the classic omission-reconstitution experiments. F3CS is a general approach for analyzing assembly and function of macromolecular complexes, especially those too large for traditional biophysical methods. PMID:22869699

Prediction of serious complications in patients with seemingly stable febrile neutropenia: validation of the Clinical Index of Stable Febrile Neutropenia in a prospective cohort of patients from the FINITE study.

PubMed

Carmona-Bayonas, Alberto; Jiménez-Fonseca, Paula; Virizuela Echaburu, Juan; Antonio, Maite; Font, Carme; Biosca, Mercè; Ramchandani, Avinash; Martínez, Jerónimo; Hernando Cubero, Jorge; Espinosa, Javier; Martínez de Castro, Eva; Ghanem, Ismael; Beato, Carmen; Blasco, Ana; Garrido, Marcelo; Bonilla, Yaiza; Mondéjar, Rebeca; Arcusa Lanza, María Ángeles; Aragón Manrique, Isabel; Manzano, Aránzazu; Sevillano, Elena; Castañón, Eduardo; Cardona, Mercé; Gallardo Martín, Elena; Pérez Armillas, Quionia; Sánchez Lasheras, Fernando; Ayala de la Peña, Francisco

2015-02-10

To validate a prognostic score predicting major complications in patients with solid tumors and seemingly stable episodes of febrile neutropenia (FN). The definition of clinical stability implies the absence of organ dysfunction, abnormalities in vital signs, and major infections. We developed the Clinical Index of Stable Febrile Neutropenia (CISNE), with six explanatory variables associated with serious complications: Eastern Cooperative Oncology Group performance status ≥ 2 (2 points), chronic obstructive pulmonary disease (1 point), chronic cardiovascular disease (1 point), mucositis of grade ≥ 2 (National Cancer Institute Common Toxicity Criteria; 1 point), monocytes < 200 per μL (1 point), and stress-induced hyperglycemia (2 points). We integrated these factors into a score ranging from 0 to 8, which classifies patients into three prognostic classes: low (0 points), intermediate (1 to 2 points), and high risk (≥ 3 points). We present a multicenter validation of CISNE. We prospectively recruited 1,133 patients with seemingly stable FN from 25 hospitals. Complication rates in the training and validation subsets, respectively, were 1.1% and 1.1% in low-, 6.1% and 6.2% in intermediate-, and 32.5% and 36% in high-risk patients; mortality rates within each class were 0% in low-, 1.6% and 0% in intermediate-, and 4.3% and 3.1% in high-risk patients. Areas under the receiver operating characteristic curves in the validation subset were 0.652 (95% CI, 0.598 to 0.703) for Talcott, 0.721 (95% CI, 0.669 to 0.768) for Multinational Association for Supportive Care in Cancer (MASCC), and 0.868 (95% CI, 0.827 to 0.903) for CISNE (P = .002 for comparison between CISNE and MASCC). CISNE is a valid model for accurately classifying patients with cancer with seemingly stable FN episodes. © 2015 by American Society of Clinical Oncology.

X-Ray Binaries and Star Clusters in the Antennae: Optical Cluster Counterparts

NASA Astrophysics Data System (ADS)

Rangelov, Blagoy; Chandar, Rupali; Prestwich, Andrea; Whitmore, Bradley C.

2012-10-01

We compare the locations of 82 X-ray binaries (XRBs) detected in the merging Antennae galaxies by Zezas et al., based on observations taken with the Chandra X-Ray Observatory, with a catalog of optically selected star clusters presented by Whitmore et al., based on observations taken with the Hubble Space Telescope. Within the 2σ positional uncertainty of ≈0farcs8, we find 22 XRBs are coincident with star clusters, where only two to three chance coincidences are expected. The ages of the clusters were estimated by comparing their UBVI, Hα colors with predictions from stellar evolutionary models. We find that 14 of the 22 coincident XRBs (64%) are hosted by star clusters with ages of ≈6 Myr or less. All of the very young host clusters are fairly massive and have M >~ 3 × 104 M ⊙, with many having masses M ≈ 105 M ⊙. Five of the XRBs are hosted by young clusters with ages τ ≈ 10-100 Myr, while three are hosted by intermediate-age clusters with τ ≈ 100-300 Myr. Based on the results from recent N-body simulations, which suggest that black holes are far more likely to be retained within their parent clusters than neutron stars, we suggest that our sample consists primarily of black hole binaries with different ages.

URS DataBase: universe of RNA structures and their motifs.

PubMed

Baulin, Eugene; Yacovlev, Victor; Khachko, Denis; Spirin, Sergei; Roytberg, Mikhail

2016-01-01

The Universe of RNA Structures DataBase (URSDB) stores information obtained from all RNA-containing PDB entries (2935 entries in October 2015). The content of the database is updated regularly. The database consists of 51 tables containing indexed data on various elements of the RNA structures. The database provides a web interface allowing user to select a subset of structures with desired features and to obtain various statistical data for a selected subset of structures or for all structures. In particular, one can easily obtain statistics on geometric parameters of base pairs, on structural motifs (stems, loops, etc.) or on different types of pseudoknots. The user can also view and get information on an individual structure or its selected parts, e.g. RNA-protein hydrogen bonds. URSDB employs a new original definition of loops in RNA structures. That definition fits both pseudoknot-free and pseudoknotted secondary structures and coincides with the classical definition in case of pseudoknot-free structures. To our knowledge, URSDB is the first database supporting searches based on topological classification of pseudoknots and on extended loop classification.Database URL: http://server3.lpm.org.ru/urs/. © The Author(s) 2016. Published by Oxford University Press.

A Deficit in Older Adults' Effortful Selection of Cued Responses

PubMed Central

Proctor, Robert W.; Vu, Kim-Phuong L.; Pick, David F.

2007-01-01

J. J. Adam et al. (1998) provided evidence for an “age-related deficit in preparing 2 fingers on 2 hands, but not on 1 hand” (p. 870). Instead of having an anatomical basis, the deficit could result from the effortful processing required for individuals to select cued subsets of responses that do not coincide with left and right subgroups. The deficit also could involve either the ultimate benefit that can be attained or the time required to attain that benefit. The authors report 3 experiments (Ns = 40, 48, and 32 participants, respectively) in which they tested those distinctions by using an overlapped hand placement (participants alternated the index and middle fingers of the hands), a normal hand placement, and longer precuing intervals than were used in previous studies. The older adults were able to achieve the full precuing benefit shown by younger adults but required longer to achieve the maximal benefit for most pairs of responses. The deficit did not depend on whether the responses were from different hands, suggesting that it lies primarily in the effortful processing required for those subsets of cued responses that are not selected easily. PMID:16801319

URS DataBase: universe of RNA structures and their motifs

PubMed Central

Baulin, Eugene; Yacovlev, Victor; Khachko, Denis; Spirin, Sergei; Roytberg, Mikhail

2016-01-01

The Universe of RNA Structures DataBase (URSDB) stores information obtained from all RNA-containing PDB entries (2935 entries in October 2015). The content of the database is updated regularly. The database consists of 51 tables containing indexed data on various elements of the RNA structures. The database provides a web interface allowing user to select a subset of structures with desired features and to obtain various statistical data for a selected subset of structures or for all structures. In particular, one can easily obtain statistics on geometric parameters of base pairs, on structural motifs (stems, loops, etc.) or on different types of pseudoknots. The user can also view and get information on an individual structure or its selected parts, e.g. RNA–protein hydrogen bonds. URSDB employs a new original definition of loops in RNA structures. That definition fits both pseudoknot-free and pseudoknotted secondary structures and coincides with the classical definition in case of pseudoknot-free structures. To our knowledge, URSDB is the first database supporting searches based on topological classification of pseudoknots and on extended loop classification. Database URL: http://server3.lpm.org.ru/urs/ PMID:27242032

On optimal fuzzy best proximity coincidence points of fuzzy order preserving proximal Ψ(σ, α)-lower-bounding asymptotically contractive mappings in non-Archimedean fuzzy metric spaces.

PubMed

De la Sen, Manuel; Abbas, Mujahid; Saleem, Naeem

2016-01-01

This paper discusses some convergence properties in fuzzy ordered proximal approaches defined by [Formula: see text]-sequences of pairs, where [Formula: see text] is a surjective self-mapping and [Formula: see text] where Aand Bare nonempty subsets of and abstract nonempty set X and [Formula: see text] is a partially ordered non-Archimedean fuzzy metric space which is endowed with a fuzzy metric M, a triangular norm * and an ordering [Formula: see text] The fuzzy set M takes values in a sequence or set [Formula: see text] where the elements of the so-called switching rule [Formula: see text] are defined from [Formula: see text] to a subset of [Formula: see text] Such a switching rule selects a particular realization of M at the nth iteration and it is parameterized by a growth evolution sequence [Formula: see text] and a sequence or set [Formula: see text] which belongs to the so-called [Formula: see text]-lower-bounding mappings which are defined from [0, 1] to [0, 1]. Some application examples concerning discrete systems under switching rules and best approximation solvability of algebraic equations are discussed.

Effects of methyltestosterone on immunity against Salmonella Pullorum in dwarf chicks.

PubMed

Li, H; Zhang, Y; Zuo, S F; Lian, Z X; Li, N

2009-12-01

This study was conducted to determine effects of methyltestosterone on innate immunity and adaptive immunity against Salmonella Pullorum in dwarf chicks. In vivo experiment, comparisons of pathological sections, viable counts of bacteria, specific antibody levels, and subsets of T lymphocytes were set forth between chicks with or without 10(-7) M methyltestosterone treatment (2 d of age through 21 d of age) and challenged with 5 x 10(8) virulent Salmonella Pullorum (7 d of age), and in vitro experiment, phagocytic and killing abilities, reactive oxygen intermediate production, and reactive nitrogen intermediate production of monocytes-macrophages treated with high (10(-8) M/10(6) cell) or physiological (10(-14) M/10(6) cell) concentration of methyltestosterone were examined after Salmonella Pullorum infection. The results showed that (1) in vivo, administration of methyltestosterone enhanced susceptibility to Salmonella Pullorum infection and depressed cellular immunity against Salmonella Pullorum, whereas it had no effect on humoral immunity in dwarf chicks; (2) in vitro, at high concentration, methyltestosterone reduced (P < 0.05) monocytes-macrophages mediated reactive oxygen intermediate-dependent killing of Salmonella Pullorum, whereas low concentration of methyltestosterone enhanced (P < 0.05) reactive oxygen intermediate-dependent killing of Salmonella Pullorum in male dwarf chicks but not in females; and (3) although challenged with Salmonella Pullorum, phagocytic ability and monocytes-macrophages mediated reactive nitrogen intermediate-dependent killing were not affected by methyltestosterone in vitro. The results indicated that methyltestosterone affected the immune response to Salmonella Pullorum in dwarf chicks by changing monocytes-macrophages mediated reactive oxygen intermediate-dependent killing and cellular immunity, and the effects were dose-dependent; furthermore, the former 2 pathways played important roles in preventing Salmonella Pullorum infection in dwarf chicks, although the mechanism needs further study.

Flow cytometric analysis of extracellular vesicle subsets in plasma: impact of swarm by particles of non-interest.

PubMed

Libregts, S F W M; Arkesteijn, G J A; Németh, A; Nolte-'t Hoen, E N M; Wauben, M H M

2018-05-20

Essentials Extracellular vesicles (EVs) in biological fluids are promising biomarkers for disease. Fluorescence-based flow cytometric analysis is suitable to detect low abundant EV subsets. Particles of non-interest can induce false-positive light scatter and fluorescent signals. Interference of particles of non-interest can be monitored by analyzing serial dilutions. Background Extracellular vesicles (EVs) in plasma are increasingly being recognized as potential biomarkers. EV analysis for diagnostic purposes should be robust and should allow analysis of EV subsets with a wide range of abundance and in a large number of patient samples. Flow cytometry offers possibilities to meet these criteria, as it allows multiparameter analysis of individual EVs. However, analysis of plasma EVs is challenging, because of their size and heterogeneity, and the presence of other submicrometer-sized particles in plasma that could interfere with EV analysis. Objectives To explore whether fluorescence-based flow cytometric analysis of EV subsets is suitable when the EVs of interest are present in low abundance in a background of non-labeled or differently labeled EVs and particles. Methods Fluorescently labeled EVs of interest were spiked at different ratios in full plasma, purified plasma components, or (non-)fluorescent polystyrene beads, and subsequently analyzed by flow cytometry with fluorescence threshold triggering. Results We found that light scatter detection of low-abundance or rare EV subsets during fluorescence threshold triggering was severely affected by particles of non-interest, owing to coincidence and swarming. Importantly, we show that interfering particles labeled with different fluorophores induced false-positive fluorescent signals on the particles of interest. These unwanted effects could only be discerned and controlled by performing serial dilutions and analyzing light scatter and fluorescence parameters. Conclusions We demonstrate how particles of non-interest in plasma can impact on the light scatter and fluorescence detection of low-abundance EVs of interest during fluorescence-based flow cytometric analysis, and provide a means to prevent erroneous data interpretation. © 2018 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Wetland paleoecological study of southwest coastal Louisiana: sediment cores and diatom calibration dataset

USGS Publications Warehouse

Smith, Kathryn E. L.; Flocks, James G.; Steyer, Gregory D.; Piazza, Sarai C.

2015-01-01

Wetland sediment data were collected in 2009 and 2010 throughout the southwest Louisiana Chenier Plain as part of a pilot study to develop a diatom-based proxy for past wetland water chemistry and the identification of sediment deposits from tropical storms. The complete dataset includes forty-six surface sediment samples and nine sediment cores. The surface sediment samples were collected in fresh, intermediate, and brackish marsh and are located coincident with Coastwide Reference Monitoring System (CRMS) sites. The nine sediment cores were collected at the Rockefeller Wildlife Refuge (RWR) located in Grand Chenier, La.

Experimental observation of the asymmetric instability of intermediate-reduced-volume vesicles in extensional flow.

PubMed

Dahl, Joanna B; Narsimhan, Vivek; Gouveia, Bernardo; Kumar, Sanjay; Shaqfeh, Eric S G; Muller, Susan J

2016-04-20

Vesicles provide an attractive model system to understand the deformation of living cells in response to mechanical forces. These simple, enclosed lipid bilayer membranes are suitable for complementary theoretical, numerical, and experimental analysis. A recent study [Narsimhan, Spann, Shaqfeh, J. Fluid Mech., 2014, 750, 144] predicted that intermediate-aspect-ratio vesicles extend asymmetrically in extensional flow. Upon infinitesimal perturbation to the vesicle shape, the vesicle stretches into an asymmetric dumbbell with a cylindrical thread separating the two ends. While the symmetric stretching of high-aspect-ratio vesicles in extensional flow has been observed and characterized [Kantsler, Segre, Steinberg, Phys. Rev. Lett., 2008, 101, 048101] as well as recapitulated in numerical simulations by Narsimhan et al., experimental observation of the asymmetric stretching has not been reported. In this work, we present results from microfluidic cross-slot experiments observing this instability, along with careful characterization of the flow field, vesicle shape, and vesicle bending modulus. The onset of this shape transition depends on two non-dimensional parameters: reduced volume (a measure of vesicle asphericity) and capillary number (ratio of viscous to bending forces). We observed that every intermediate-reduced-volume vesicle that extends forms a dumbbell shape that is indeed asymmetric. For the subset of the intermediate-reduced-volume regime we could capture experimentally, we present an experimental phase diagram for asymmetric vesicle stretching that is consistent with the predictions of Narsimhan et al.

Speciation, Divergence, and the Origin of Gryllus rubens: Behavior, Morphology, and Molecules

PubMed Central

Gray, David A.

2011-01-01

The last 25 years or so has seen a huge resurgence of interest in speciation research. This has coincided with the development and widespread use of new tools in molecular genetics, especially DNA sequencing, to inform ecological and evolutionary questions. Here I review about a decade of work on the sister species of field crickets Gryllus texensis and G. rubens. This work has included analysis of morphology, behavior, and the mitochondrial DNA molecule. The molecular work in particular has dramatically re-shaped my interpretation of the speciational history of these taxa, suggesting that rather than ‘sister’ species we should consider these taxa as ‘mother-daughter’ species with G. rubens derived from within a subset of ancestral G. texensis. PMID:26467622

Observations of Dynamic Strain Aging in Polycrystalline NiAl

NASA Technical Reports Server (NTRS)

Weaver, M. L.; Noebe, R. D.; Kaufman, M. J.

1996-01-01

Dynamic strain aging has been investigated at temperatures between 77 and 1100 K in eight polycrystalline NiAl alloys. The 0.2% offset yield stress and work hardening rates for these alloys generally decreased with increasing temperature. However, local plateaus or maxima were observed in conventional purity and carbon doped alloys at intermediate temperatures (600-900 K). This anomalous behavior was not observed in low interstitial high-purity, nitrogen doped, or in titanium doped materials. Low or negative strain rate sensitivities (SRS) were also observed in all eight alloys in this intermediate temperature range. Coincident with the occurrence of negative SRS was the occurrence of serrated flow in conventional purity alloys containing high concentrations of Si in addition to C. These phenomena have been attributed to dynamic strain aging (DSA). Chemical analysis of the alloys used in this study suggests that the main species causing strain aging in polycrystalline NiAl is C but indicate that residual Si impurities can enhance the strain aging effect.

Short-range magentic correlations and dynamic orbital ordering in the thermally activated spin state of LaCoO3

NASA Astrophysics Data System (ADS)

Rosenkranz, S.; Phelan, D.; Louca, D.; Lee, S. H.; Chupas, P. J.; Osborn, R.; Zheng, H.; Mitchell, J. F.

2006-03-01

The cobalt perovskites La1-xSrxCoO3 show intriguing spin, lattice, and orbital properties similar to the ones observed in colossal magnetoresistive manganites. The x=0 parent compound is a non-magnetic insulator at low temperatures, but shows evidence of a spin-state transition of the cobalt ions above 50K from a low-spin to an intermediate or high-spin configuration. Using high resolution, inelastic neutron scattering, we observe a distinct low energy excitation at 0.6meV coincident with the thermally induced spin state transition observed in susceptibility measurements. The thermal activation of this excited spin state also leads to short-range, dynamic ferro- and antiferromagnetic correlations. These observations are consistent with the activation of a zero-field split intermediate spin state as well as the presence of dynamic orbital ordering of these excited states. Work supported by US DOE BES-DMS W-31-109-ENG-38 and NSF DMR-0454672

Estimation of the intrinsic absorption and scattering attenuation in Northeastern Venezuela (Southeastern Caribbean) using coda waves

USGS Publications Warehouse

Ugalde, A.; Pujades, L.G.; Canas, J.A.; Villasenor, A.

1998-01-01

Northeastern Venezuela has been studied in terms of coda wave attenuation using seismograms from local earthquakes recorded by a temporary short-period seismic network. The studied area has been separated into two subregions in order to investigate lateral variations in the attenuation parameters. Coda-Q-1 (Q(c)-1) has been obtained using the single-scattering theory. The contribution of the intrinsic absorption (Q(i)-1) and scattering (Q(s)-1) to total attenuation (Q(t)-1) has been estimated by means of a multiple lapse time window method, based on the hypothesis of multiple isotropic scattering with uniform distribution of scatterers. Results show significant spatial variations of attenuation: the estimates for intermediate depth events and for shallow events present major differences. This fact may be related to different tectonic characteristics that may be due to the presence of the Lesser Antilles subduction zone, because the intermediate depth seismic zone may be coincident with the southern continuation of the subducting slab under the arc.

Radio Sources Associated with Intermediate X-ray Luminosity Objects in Merging Galaxy Systems

NASA Technical Reports Server (NTRS)

Neff, S. G.; Ulvestad, J. S.; Oegerle, William R. (Technical Monitor)

2002-01-01

We present new, high-resolution 6, 3.6, and 2 cm radio images of a time-ordered sequence of merging galaxy systems. The new data have a resolution of less than 100pc and a sensitivity comparable to a few x Cas A. We detect compact radio sources in all systems, generally embedded in more diffuse radio emission at the longer wavelengths. Several of the compact radio sources are coincident with compact Intermediate-luminosity X-ray Objects (IXOs) in these systems, and many more are within the 3$/sigma$ Chandra position errors for other IXOs. The fraction of radio identifications and the nature of the radio sources changes as a function of merger stage. These data suggest that the IXOs are associated with complexes of supernova remnants, and therefore with star formation that has occurred within the last $/sim$10$circumflex7$ yr, but are not located in HII regions where copious star formation is occurring currently.

Whole-body γ-irradiation decelerates rat hepatocyte polyploidization.

PubMed

Ikhtiar, Adnan M

2015-07-01

To characterize hepatocyte polyploidization induced by intermediate dose of γ-ray. Male Wistar strain rats were whole-body irradiated (WBI) with 2 Gy of γ-ray at the age of 1 month, and 5-6 rats were sacrificed monthly at 0-25 months after irradiation. The nuclear DNA content of individual hepatocytes was measured by flow cytometry, then hepatocytes were classified into various ploidy classes. Survival percentage, after exposure up to the end of the study, did not indicate any differences between the irradiated groups and controls. The degree of polyploidization in hepatocytes of irradiated rats, was significantly lower than that for the control after 1 month of exposure, and it continued to be lower after up to 8 months. Thereafter, the degree of polyploidization in the irradiated group slowly returned to the control level when the irradiated rats reached the age of 10 months. Intermediate dose of ionizing radiation, in contrast to high doses, decelerate hepatocyte polyploidization, which may coincides with the hypothesis of the beneficial effects of low doses of ionizing radiation.

The rough energy landscape of superfolder GFP is linked to the chromophore

PubMed Central

Andrews, Benjamin T.; Schoenfish, Andrea R.; Roy, Melinda; Waldo, Geoffrey; Jennings, Patricia A.

2009-01-01

Many GFP variants have been developed for use as fluorescent tags, and recently a superfolder GFP (sfGFP) has been developed as a robust folding reporter. This new variant shows increased stability and improved folding kinetics, as well as 100% recovery of native protein after denaturation. Here, we characterize sfGFP, and find that this variant exhibits hysteresis as unfolding and refolding equilibrium titration curves are non-coincident even after equilibration for more than eight half-lives as estimated from kinetic unfolding and refolding studies. This hysteresis is attributed to trapping in a native-like intermediate state. Mutational studies directed towards inhibiting chromophore formation indicate that the novel backbone cyclization is responsible for the hysteresis observed in equilibrium titrations of sfGFP. Slow equilibration and the presence of intermediates imply a rough landscape. However, de novo folding in the absence of the chromophore is dominated by a smoother energy landscape than that sampled during unfolding and refolding of the post-translationally modified polypeptide. PMID:17822714

A non cool-core 4.6-keV cluster around the bright nearby radio galaxy PKS B1416-493

NASA Astrophysics Data System (ADS)

Worrall, D. M.; Birkinshaw, M.

2017-05-01

We present new X-ray (Chandra) and radio (ATCA) observations of the z = 0.09 radio galaxy PKS B1416-493, a member of the southern equivalent of the 3CRR sample. We find the source to be embedded in a previously unrecognized bright kT = 4.6-keV non cool-core cluster. The discovery of new clusters of such high temperature and luminosity within z = 0.1 is rare. The radio source was chosen for observation based on its intermediate FR I/II morphology. We identify a cavity coincident with the northeast lobe, and excess counts associated with the southwest lobe that we interpret as inverse-Compton X-ray emission. The jet power, at 5.3 × 1044 erg s-1, when weighted by radio source density, supports suggestions that radio sources of intermediate morphology and radio power may dominate radio-galaxy heating in the local Universe.

Paleoclimatic analyses of middle Eocene through Oligocene planktic foraminiferal faunas

USGS Publications Warehouse

Keller, G.

1983-01-01

Quantitative faunal analyses and oxygen isotope ranking of individual planktic foraminiferal species from deep sea sequences of three oceans are used to make paleoceanographic and paleoclimatic inferences. Species grouped into surface, intermediate and deep water categories based on ??18O values provide evidence of major changes in water-mass stratification, and individual species abundances indicate low frequency cool-warm oscillations. These data suggest that relatively stable climatic phases with minor cool-warm oscillations of ???0.5 m.y. frequency are separated by rapid cooling events during middle Eocene to early Oligocene time. Five major climatic phases are evident in the water-mass stratification between middle Eocene through Oligocene time. Phase changes occur at P14/P15, P15/P16, P20/P21 and P21/P22 Zone boundaries and are marked by major faunal turnovers, rapid cooling in the isotope record, hiatuses and changes in the eustatic sea level. A general cooling trend between middle Eocene to early late Oligocene is indicated by the successive replacement of warm middle Eocene surface water species by cooler late Eocene intermediate water species and still cooler Oligocene intermediate and deep water species. Increased water-mass stratification in the latest Eocene (P17), indicated by the coexistence of surface, intermediate and deep dwelling species groups, suggest that increased thermal gradients developed between the equator and poles nearly coincident with the development of the psychrosphere. This pattern may be related to significant ice accumulation between late Eocene and early late Oligocene time. ?? 1983.

Robust Likelihoods for Inflationary Gravitational Waves from Maps of Cosmic Microwave Background Polarization

NASA Technical Reports Server (NTRS)

Switzer, Eric Ryan; Watts, Duncan J.

2016-01-01

The B-mode polarization of the cosmic microwave background provides a unique window into tensor perturbations from inflationary gravitational waves. Survey effects complicate the estimation and description of the power spectrum on the largest angular scales. The pixel-space likelihood yields parameter distributions without the power spectrum as an intermediate step, but it does not have the large suite of tests available to power spectral methods. Searches for primordial B-modes must rigorously reject and rule out contamination. Many forms of contamination vary or are uncorrelated across epochs, frequencies, surveys, or other data treatment subsets. The cross power and the power spectrum of the difference of subset maps provide approaches to reject and isolate excess variance. We develop an analogous joint pixel-space likelihood. Contamination not modeled in the likelihood produces parameter-dependent bias and complicates the interpretation of the difference map. We describe a null test that consistently weights the difference map. Excess variance should either be explicitly modeled in the covariance or be removed through reprocessing the data.

A Coincidence Detection Mechanism Controls PX-BAR Domain-Mediated Endocytic Membrane Remodeling via an Allosteric Structural Switch.

PubMed

Lo, Wen-Ting; Vujičić Žagar, Andreja; Gerth, Fabian; Lehmann, Martin; Puchkov, Dymtro; Krylova, Oxana; Freund, Christian; Scapozza, Leonardo; Vadas, Oscar; Haucke, Volker

2017-11-20

Clathrin-mediated endocytosis occurs by bending and remodeling of the membrane underneath the coat. Bin-amphiphysin-rvs (BAR) domain proteins are crucial for endocytic membrane remodeling, but how their activity is spatiotemporally controlled is largely unknown. We demonstrate that the membrane remodeling activity of sorting nexin 9 (SNX9), a late-acting endocytic PX-BAR domain protein required for constriction of U-shaped endocytic intermediates, is controlled by an allosteric structural switch involving coincident detection of the clathrin adaptor AP2 and phosphatidylinositol-3,4-bisphosphate (PI(3,4)P 2 ) at endocytic sites. Structural, biochemical, and cell biological data show that SNX9 is autoinhibited in solution. Binding to PI(3,4)P 2 via its PX-BAR domain, and concomitant association with AP2 via sequences in the linker region, releases SNX9 autoinhibitory contacts to enable membrane constriction. Our results reveal a mechanism for restricting the latent membrane remodeling activity of BAR domain proteins to allow spatiotemporal coupling of membrane constriction to the progression of the endocytic pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

A Continuum-Atomistic Analysis of Transgranular Crack Propagation in Aluminum

NASA Technical Reports Server (NTRS)

Yamakov, V.; Saether, E.; Glaessgen, E.

2009-01-01

A concurrent multiscale modeling methodology that embeds a molecular dynamics (MD) region within a finite element (FEM) domain is used to study plastic processes at a crack tip in a single crystal of aluminum. The case of mode I loading is studied. A transition from deformation twinning to full dislocation emission from the crack tip is found when the crack plane is rotated around the [111] crystallographic axis. When the crack plane normal coincides with the [112] twinning direction, the crack propagates through a twinning mechanism. When the crack plane normal coincides with the [011] slip direction, the crack propagates through the emission of full dislocations. In intermediate orientations, a transition from full dislocation emission to twinning is found to occur with an increase in the stress intensity at the crack tip. This finding confirms the suggestion that the very high strain rates, inherently present in MD simulations, which produce higher stress intensities at the crack tip, over-predict the tendency for deformation twinning compared to experiments. The present study, therefore, aims to develop a more realistic and accurate predictive modeling of fracture processes.

Decipher the mechanisms of protein conformational changes induced by nucleotide binding through free-energy landscape analysis: ATP binding to Hsp70.

PubMed

Nicolaï, Adrien; Delarue, Patrice; Senet, Patrick

2013-01-01

ATP regulates the function of many proteins in the cell by transducing its binding and hydrolysis energies into protein conformational changes by mechanisms which are challenging to identify at the atomic scale. Based on molecular dynamics (MD) simulations, a method is proposed to analyze the structural changes induced by ATP binding to a protein by computing the effective free-energy landscape (FEL) of a subset of its coordinates along its amino-acid sequence. The method is applied to characterize the mechanism by which the binding of ATP to the nucleotide-binding domain (NBD) of Hsp70 propagates a signal to its substrate-binding domain (SBD). Unbiased MD simulations were performed for Hsp70-DnaK chaperone in nucleotide-free, ADP-bound and ATP-bound states. The simulations revealed that the SBD does not interact with the NBD for DnaK in its nucleotide-free and ADP-bound states whereas the docking of the SBD was found in the ATP-bound state. The docked state induced by ATP binding found in MD is an intermediate state between the initial nucleotide-free and final ATP-bound states of Hsp70. The analysis of the FEL projected along the amino-acid sequence permitted to identify a subset of 27 protein internal coordinates corresponding to a network of 91 key residues involved in the conformational change induced by ATP binding. Among the 91 residues, 26 are identified for the first time, whereas the others were shown relevant for the allosteric communication of Hsp70 s in several experiments and bioinformatics analysis. The FEL analysis revealed also the origin of the ATP-induced structural modifications of the SBD recently measured by Electron Paramagnetic Resonance. The pathway between the nucleotide-free and the intermediate state of DnaK was extracted by applying principal component analysis to the subset of internal coordinates describing the transition. The methodology proposed is general and could be applied to analyze allosteric communication in other proteins.

Decipher the Mechanisms of Protein Conformational Changes Induced by Nucleotide Binding through Free-Energy Landscape Analysis: ATP Binding to Hsp70

PubMed Central

Nicolaï, Adrien; Delarue, Patrice; Senet, Patrick

2013-01-01

ATP regulates the function of many proteins in the cell by transducing its binding and hydrolysis energies into protein conformational changes by mechanisms which are challenging to identify at the atomic scale. Based on molecular dynamics (MD) simulations, a method is proposed to analyze the structural changes induced by ATP binding to a protein by computing the effective free-energy landscape (FEL) of a subset of its coordinates along its amino-acid sequence. The method is applied to characterize the mechanism by which the binding of ATP to the nucleotide-binding domain (NBD) of Hsp70 propagates a signal to its substrate-binding domain (SBD). Unbiased MD simulations were performed for Hsp70-DnaK chaperone in nucleotide-free, ADP-bound and ATP-bound states. The simulations revealed that the SBD does not interact with the NBD for DnaK in its nucleotide-free and ADP-bound states whereas the docking of the SBD was found in the ATP-bound state. The docked state induced by ATP binding found in MD is an intermediate state between the initial nucleotide-free and final ATP-bound states of Hsp70. The analysis of the FEL projected along the amino-acid sequence permitted to identify a subset of 27 protein internal coordinates corresponding to a network of 91 key residues involved in the conformational change induced by ATP binding. Among the 91 residues, 26 are identified for the first time, whereas the others were shown relevant for the allosteric communication of Hsp70 s in several experiments and bioinformatics analysis. The FEL analysis revealed also the origin of the ATP-induced structural modifications of the SBD recently measured by Electron Paramagnetic Resonance. The pathway between the nucleotide-free and the intermediate state of DnaK was extracted by applying principal component analysis to the subset of internal coordinates describing the transition. The methodology proposed is general and could be applied to analyze allosteric communication in other proteins. PMID:24348227

X-RAY BINARIES AND STAR CLUSTERS IN THE ANTENNAE: OPTICAL CLUSTER COUNTERPARTS

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

Rangelov, Blagoy; Chandar, Rupali; Prestwich, Andrea

2012-10-20

We compare the locations of 82 X-ray binaries (XRBs) detected in the merging Antennae galaxies by Zezas et al., based on observations taken with the Chandra X-Ray Observatory, with a catalog of optically selected star clusters presented by Whitmore et al., based on observations taken with the Hubble Space Telescope. Within the 2{sigma} positional uncertainty of Almost-Equal-To 0.''8, we find 22 XRBs are coincident with star clusters, where only two to three chance coincidences are expected. The ages of the clusters were estimated by comparing their UBVI, H{alpha} colors with predictions from stellar evolutionary models. We find that 14 ofmore » the 22 coincident XRBs (64%) are hosted by star clusters with ages of Almost-Equal-To 6 Myr or less. All of the very young host clusters are fairly massive and have M {approx}> 3 Multiplication-Sign 10{sup 4} M {sub Sun }, with many having masses M Almost-Equal-To 10{sup 5} M {sub Sun }. Five of the XRBs are hosted by young clusters with ages {tau} Almost-Equal-To 10-100 Myr, while three are hosted by intermediate-age clusters with {tau} Almost-Equal-To 100-300 Myr. Based on the results from recent N-body simulations, which suggest that black holes are far more likely to be retained within their parent clusters than neutron stars, we suggest that our sample consists primarily of black hole binaries with different ages.« less

Is there another coincidence problem at the reionization epoch?

NASA Astrophysics Data System (ADS)

Lombriser, Lucas; Smer-Barreto, Vanessa

2017-12-01

The cosmological coincidences between the matter and radiation energy densities at recombination as well as between the densities of matter and the cosmological constant at the present time are well known. We point out that, moreover, the third intersection between the energy densities of radiation and the cosmological constant coincides with the reionization epoch. To quantify the statistical relevance of this concurrence, we compute the Bayes factor between the concordance cosmology with free Thomson scattering optical depth and a model for which this parameter is inferred from imposing a match between the time of density equality and the epoch of reionization. This is to characterize the potential explanatory gain if one were to find a parameter-free physical connection. We find a very strong preference for such a concurrence on the Jeffreys scale from current cosmological observations. We furthermore discuss the effect of the choice of priors, changes in reionization history, and free sum of neutrino masses. We also estimate the impact of adding intermediate polarization data from the Planck High Frequency Instrument and prospects for future 21 cm surveys. In the first case, the preference for the correlation remains substantial, whereas future data may give results more decisive in pro or substantial in contra of it. Finally, we provide a discussion on different interpretations of these findings. In particular, we show how a connection between the star-formation history and the cosmological background dynamics can give rise to this concurrence.

Molecular Analysis of Non-Small Cell Lung Cancer (NSCLC) Identifies Subsets with Different Sensitivity to Insulin like Growth Factor I Receptor (IGF-IR) Inhibition

PubMed Central

Gualberto, Antonio; Dolled-Filhart, Marisa; Gustavson, Mark; Christiansen, Jason; Wang, Yu-Fen; Hixon, Mary L.; Reynolds, Jennifer; McDonald, Sandra; Ang, Agnes; Rimm, David L.; Langer, Corey J.; Blakely, Johnetta; Garland, Linda; Paz-Ares, Luis G.; Karp, Daniel D.; Lee, Adrian V.

2010-01-01

Purpose Identify molecular determinants of sensitivity of NSCLC to anti-insulin like growth factor receptor (IGF-IR) therapy. Experimental Design 216 tumor samples were investigated. 165 consisted of retrospective analyses of banked tissue and an additional 51 were from patients enrolled in a phase 2 study of figitumumab (F), a monoclonal antibody against the IGF-IR, in stage IIIb/IV NSCLC. Biomarkers assessed included IGF-IR, EGFR, IGF-2, IGF-2R, IRS-1, IRS-2, vimentin and E-cadherin. Sub-cellular localization of IRS-1 and phosphorylation levels of MAPK and Akt1 were also analyzed. Results IGF-IR was differentially expressed across histological subtypes (P=0.04), with highest levels observed in squamous cell tumors. Elevated IGF-IR expression was also observed in a small number of squamous cell tumors responding to chemotherapy combined with F (p=0.008). Since no other biomarker/response interaction was observed using classical histological sub-typing, a molecular approach was undertaken to segment NSCLC into mechanism-based subpopulations. Principal component analysis and unsupervised Bayesian clustering identified 3 NSCLC subsets that resembled the steps of the epithelial-to-mesenchymal transition: E-cadherin high/IRS-1 low (Epithelial-like), E-cadherin intermediate/IRS-1 high (Transitional) and E-cadherin low/IRS-1 low (Mesenchymal-like). Several markers of the IGF-IR pathway were over-expressed in the Transitional subset. Furthermore, a higher response rate to the combination of chemotherapy and F was observed in Transitional tumors (71%) compared to those in the Mesenchymal-like subset (32%, p=0.03). Only one Epithelial-like tumor was identified in the phase 2 study, suggesting that advanced NSCLC has undergone significant de-differentiation at diagnosis. Conclusion NSCLC comprises molecular subsets with differential sensitivity to IGF-IR inhibition. PMID:20670944

Corridor of existence of thermodynamically consistent solution of the Ornstein-Zernike equation.

PubMed

Vorob'ev, V S; Martynov, G A

2007-07-14

We obtain the exact equation for a correction to the Ornstein-Zernike (OZ) equation based on the assumption of the uniqueness of thermodynamical functions. We show that this equation is reduced to a differential equation with one arbitrary parameter for the hard sphere model. The compressibility factor within narrow limits of this parameter variation can either coincide with one of the formulas obtained on the basis of analytical solutions of the OZ equation or assume all intermediate values lying in a corridor between these solutions. In particular, we find the value of this parameter when the thermodynamically consistent compressibility factor corresponds to the Carnahan-Stirling formula.

Synthesis of Resveratrol Tetramers via a Stereoconvergent Radical Equilibrium

PubMed Central

Keylor, Mitchell H.; Matsuura, Bryan S.; Griesser, Markus; Chauvin, Jean-Philippe R.; Harding, Ryan A.; Kirillova, Mariia S.; Zhu, Xu; Fischer, Oliver J.; Pratt, Derek A.; Stephenson, Corey R. J.

2017-01-01

Persistent free radicals have become indispensable in the synthesis of organic materials by living radical polymerization. However, examples of their use in the synthesis of small molecules are rare. Herein, we report the application of persistent radical and quinone methide intermediates to the synthesis of the resveratrol tetramers nepalensinol B and vateriaphenol C. The spontaneous cleavage and reconstitution of exceptionally weak carbon-carbon bonds has enabled a stereoconvergent oxidative dimerization of racemic materials in a transformation that likely coincides with the biogenesis of these natural products. The efficient synthesis of higher-order oligomers of resveratrol will facilitate the biological studies necessary to elucidate their mechanism(s) of action. PMID:27940867

Glyphidocythere, a new deep marine, paradoxostomatid (Ostracoda) from the Quaternary and recent of the Indo-Pacific

USGS Publications Warehouse

Ayress, M.A.; Correge, T.; Whatley, R.C.

1993-01-01

Chapman’s (1910) Pseudocythere funafutiensis from 1924m off Funafuti, western Pacific is redescribed and illustrated together with additional Pleistocene and Recent material from the Coral and Tasman seas. A new paradoxostomatid genus, Glyphidocythere, is described to accommodate it and two other species yet to be formally described from the Banda Sea, eastern Indonesia. The genus is apparently restricted to the marine slope environment of low (less than 20°) southern latitudes. In the Coral and Tasman seas G. funafutiensis occurs within a narrow bathyal depth range (955m to 1754m) coincident with the Antarctic Intermediate Water.

Biosynthesis of the phytoalexin pisatin. [Pisum sativum

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

Preisig, C.L.; Bell, J.N.; Matthews, D.E.

1990-11-01

NADPH-dependent reduction of 2{prime},7-dihydroxy-4{prime},5{prime}-methylenedioxyisoflavone to the isoflavanone sophorol, a proposed intermediate step in pisatin biosynthesis, was detected in extracts of Pisum sativum. This isoflavone reductase activity was inducible by treatment of pea seedlings with CuCl{sub 2}. The timing of induction coincided with that of the 6a-hydroxymaackiain 3-O-methyltransferase, which catalyzes the terminal biosynthetic step. Neither enzyme was light inducible. Further NADPH-dependent metabolism of sophorol by extracts of CuCl{sub 2}-treated seedlings was also observed; three products were radiolabeled when ({sup 3}H)sophorol was the substrate, one of which is tentatively identified as maackiain.

Boundary effects in a quasi-two-dimensional driven granular fluid.

PubMed

Smith, N D; Smith, M I

2017-12-01

The effect of a confining boundary on the spatial variations in granular temperature of a driven quasi-two-dimensional layer of particles is investigated experimentally. The radial drop in the relative granular temperature ΔT/T exhibits a maximum at intermediate particle numbers which coincides with a crossover from kinetic to collisional transport of energy. It is also found that at low particle numbers, the distributions of radial velocities are increasingly asymmetric as one approaches the boundary. The radial and tangential granular temperatures split, and in the tails of the radial velocity distribution there is a higher population of fast moving particles traveling away rather than towards the boundary.

Genomic Evidence that Methanotrophic Endosymbionts Likely Provide Deep-Sea Bathymodiolus Mussels with a Sterol Intermediate in Cholesterol Biosynthesis

PubMed Central

Takaki, Yoshihiro; Chikaraishi, Yoshito; Ikuta, Tetsuro; Ozawa, Genki; Yoshida, Takao; Ohkouchi, Naohiko; Fujikura, Katsunori

2017-01-01

Sterols are key cyclic triterpenoid lipid components of eukaryotic cellular membranes, which are synthesized through complex multi-enzyme pathways. Similar to most animals, Bathymodiolus mussels, which inhabit deep-sea chemosynthetic ecosystems and harbor methanotrophic and/or thiotrophic bacterial endosymbionts, possess cholesterol as their main sterol. Based on the stable carbon isotope analyses, it has been suggested that host Bathymodiolus mussels synthesize cholesterol using a sterol intermediate derived from the methanotrophic endosymbionts. To test this hypothesis, we sequenced the genome of the methanotrophic endosymbiont in Bathymodiolus platifrons. The genome sequence data demonstrated that the endosymbiont potentially generates up to 4,4-dimethyl-cholesta-8,14,24-trienol, a sterol intermediate in cholesterol biosynthesis, from methane. In addition, transcripts for a subset of the enzymes of the biosynthetic pathway to cholesterol downstream from a sterol intermediate derived from methanotroph endosymbionts were detected in our transcriptome data for B. platifrons. These findings suggest that this mussel can de novo synthesize cholesterol from methane in cooperation with the symbionts. By in situ hybridization analyses, we showed that genes associated with cholesterol biosynthesis from both host and endosymbionts were expressed exclusively in the gill epithelial bacteriocytes containing endosymbionts. Thus, cholesterol production is probably localized within these specialized cells of the gill. Considering that the host mussel cannot de novo synthesize cholesterol and depends largely on endosymbionts for nutrition, the capacity of endosymbionts to synthesize sterols may be important in establishing symbiont–host relationships in these chemosynthetic mussels. PMID:28453654

Towards Deciphering the Hidden Mechanisms That Contribute to the Antigenic Activation Process of Human Vγ9Vδ2 T Cells.

PubMed

Boutin, Lola; Scotet, Emmanuel

2018-01-01

Vγ9Vδ2 T cells represent a major unconventional γδ T cell subset located in the peripheral blood of adults in humans and several non-human primates. Lymphocytes that constitute this transitional subset can sense subtle level changes of intracellular phosphorylated intermediates of the isoprenoid biosynthesis pathway (phosphoantigens, pAg), such as isopentenyl pyrophosphate, during cell stress events. This unique antigenic activation process operates in a rigorous framework that requires the expression of butyrophilin 3A1 (BTN3A1/CD277) molecules, which are type I glycoproteins that belong to the B7 family. Several studies have further shown that pAg specifically bind to the intracellular B30.2 domain of BTN3A1 linked to the antigenic activation of Vγ9Vδ2 T cells. Here, we highlight the recent advances in BTN3A1 dynamics induced upon the binding of pAg and the contribution of the different subunits to this activation process. Recent reports support that conformational modifications of BTN3A1 might represent a key step in the detection of infection or tumorigenesis by Vγ9Vδ2 T cells. A better understanding of this mechanism will help optimize novel immunotherapeutical approaches that target defined functions of this unique γδ T cell subset.

Towards Deciphering the Hidden Mechanisms That Contribute to the Antigenic Activation Process of Human Vγ9Vδ2 T Cells

PubMed Central

Boutin, Lola; Scotet, Emmanuel

2018-01-01

Vγ9Vδ2 T cells represent a major unconventional γδ T cell subset located in the peripheral blood of adults in humans and several non-human primates. Lymphocytes that constitute this transitional subset can sense subtle level changes of intracellular phosphorylated intermediates of the isoprenoid biosynthesis pathway (phosphoantigens, pAg), such as isopentenyl pyrophosphate, during cell stress events. This unique antigenic activation process operates in a rigorous framework that requires the expression of butyrophilin 3A1 (BTN3A1/CD277) molecules, which are type I glycoproteins that belong to the B7 family. Several studies have further shown that pAg specifically bind to the intracellular B30.2 domain of BTN3A1 linked to the antigenic activation of Vγ9Vδ2 T cells. Here, we highlight the recent advances in BTN3A1 dynamics induced upon the binding of pAg and the contribution of the different subunits to this activation process. Recent reports support that conformational modifications of BTN3A1 might represent a key step in the detection of infection or tumorigenesis by Vγ9Vδ2 T cells. A better understanding of this mechanism will help optimize novel immunotherapeutical approaches that target defined functions of this unique γδ T cell subset. PMID:29731756

Effect of freezing of sputum samples on flow cytometric analysis of lymphocyte subsets.

PubMed

Jaksztat, E; Holz, O; Paasch, K; Kelly, M M; Hargreave, F E; Cox, G; Magnussen, H; Jörres, R A

2004-08-01

Sputum samples should be processed shortly after induction to prevent cell degradation. For intermediate storage, freezing of homogenised samples or immediate fixation have been shown to be suitable for cytospins. The aim of this study was to investigate whether freezing or immediate fixation of sputum affect the analysis of lymphocyte subsets by flow cytometry. Selected plugs from 24 sputum samples were homogenised. One aliquot was processed immediately and analysed by flow cytometry. A second aliquot was homogenised, frozen at -20 C after addition of dimethylsulfoxide and stored for a median time of 6 days. In six samples a third aliquot was fixed in formalin after induction and stored for up to 72 h before further processing. Compared to immediate processing, percentages of total lymphocytes and T-suppressor cells were elevated after being frozen, with a minor decrease in the T4/T8 ratio. Proportions of total lymphocytes, T-helper and T-suppressor cells correlated between native and frozen samples, intra-class correlation coefficients being 0.74, 0.85 and 0.70, respectively. The formalin-fixed aliquots could not be analysed with the antibodies used. In conclusion, freezing seems to be a suitable technique to store sputum samples for flow cytometry of CD3, CD4 and CD8 lymphocyte subsets. Its effects were minor compared to the variation between subjects.

Myelin-oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex

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

Pham-Dinh, D.; Dautigny, A.; Mattei, M.G.

1993-09-01

Myelin/oligodendrocyte glycoprotein (MOG) is found on the surface of myelinating oligodendrocytes and external lamellae of myelin sheaths in the central nervous system, and it is target antigen in experimental autoimmune encephalomyelitis and multiple sclerosis. The authors have isolated bovine, mouse, and rat MOG cDNA clones and shown that the developmental pattern of MOG expression in the rat central nervous system coincides with the late stages of myelination. The amino-terminal, extracellular domain of MOG has characteristics of an immunoglobulin variable domain and is 46% and 41% identical with the amino terminus of bovine butyrophilin (expressed in the lactating mammary gland) andmore » B-G antigens of the chicken major histocompatibility complex (MHC), respectively; these proteins thus form a subset of the immunoglobulin superfamily. The homology between MOG and B-G extends beyond their structure and genetic mapping to their ability to induce strong antibody responses and has implications for the role of MOG in pathological, autoimmune conditions. The authors colocalized the MOG and BT genes to the human MHC on chromosome 6p21.3-p22. The mouse MOG gene was mapped to the homologous band C of chromosome 17, within the M region of the mouse MHC. 38 refs., 6 figs.« less

On F-Algebras M p  (1 < p < ∞) of Holomorphic Functions

PubMed Central

Meštrović, Romeo

2014-01-01

We consider the classes M p (1 < p < ∞) of holomorphic functions on the open unit disk 𝔻 in the complex plane. These classes are in fact generalizations of the class M introduced by Kim (1986). The space M p equipped with the topology given by the metric ρ p defined by ρ p(f, g) = ||f − g||p = (∫ 0 2πlogp(1 + M(f − g)(θ))(dθ/2π))1/p, with f, g∈M p and Mf(θ) = sup0⩽r<1 ⁡|f(re iθ)|, becomes an F-space. By a result of Stoll (1977), the Privalov space N p (1 < p < ∞) with the topology given by the Stoll metric d p is an F-algebra. By using these two facts, we prove that the spaces M p and N p coincide and have the same topological structure. Consequently, we describe a general form of continuous linear functionals on M p (with respect to the metric ρ p). Furthermore, we give a characterization of bounded subsets of the spaces M p. Moreover, we give the examples of bounded subsets of M p that are not relatively compact. PMID:24672388

Modelling uncertainty with generalized credal sets: application to conjunction and decision

NASA Astrophysics Data System (ADS)

Bronevich, Andrey G.; Rozenberg, Igor N.

2018-01-01

To model conflict, non-specificity and contradiction in information, upper and lower generalized credal sets are introduced. Any upper generalized credal set is a convex subset of plausibility measures interpreted as lower probabilities whose bodies of evidence consist of singletons and a certain event. Analogously, contradiction is modelled in the theory of evidence by a belief function that is greater than zero at empty set. Based on generalized credal sets, we extend the conjunctive rule for contradictory sources of information, introduce constructions like natural extension in the theory of imprecise probabilities and show that the model of generalized credal sets coincides with the model of imprecise probabilities if the profile of a generalized credal set consists of probability measures. We give ways how the introduced model can be applied to decision problems.

The Discounted Method and Equivalence of Average Criteria for Risk-Sensitive Markov Decision Processes on Borel Spaces

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

Cavazos-Cadena, Rolando, E-mail: rcavazos@uaaan.m; Salem-Silva, Francisco, E-mail: frsalem@uv.m

2010-04-15

This note concerns discrete-time controlled Markov chains with Borel state and action spaces. Given a nonnegative cost function, the performance of a control policy is measured by the superior limit risk-sensitive average criterion associated with a constant and positive risk sensitivity coefficient. Within such a framework, the discounted approach is used (a) to establish the existence of solutions for the corresponding optimality inequality, and (b) to show that, under mild conditions on the cost function, the optimal value functions corresponding to the superior and inferior limit average criteria coincide on a certain subset of the state space. The approach ofmore » the paper relies on standard dynamic programming ideas and on a simple analytical derivation of a Tauberian relation.« less

Topological Ordering and Viscosity in the Glassy Ge-Se System: The Search for a Structural or Dynamical Signature of the Intermediate Phase

NASA Astrophysics Data System (ADS)

Zeidler, Anita; Salmon, Philip S.; Whittaker, Dean A. J.; Pizzey, Keiron J.; Hannon, Alex C.

2017-11-01

The topological ordering of the network structure in vitreous Ge_xSe_{1-x} was investigated across most of the glass-forming region (0 ≤ x ≤ 0.4) by using high-resolution neutron diffraction to measure the Bhatia-Thornton number-number partial structure factor. This approach gives access to the composition dependence of the mean coordination number \\bar{n} and correlation lengths associated with the network ordering. The thermal properties of the samples were also measured by using temperature-modulated differential scanning calorimetry. The results do not point to a structural origin of the so-called intermediate phase, which in our work is indicated for the composition range 0.175(8) ≤ x ≤ 0.235(8) by a vanishingly-small non-reversing enthalpy near the glass transition. The midpoint of this range coincides with the mean-field expectation of a floppy-to-rigid transition at x = 0.20. The composition dependence of the liquid viscosity, as taken from the literature, was also investigated to look for a dynamical origin of the intermediate phase, using the Mauro-Yue-Ellison-Gupta-Allan (MYEGA) model to estimate the viscosity at the liquidus temperature. The evidence points to a maximum in the viscosity at the liquidus temperature, and a minimum in the fragility index, for the range 0.20 ≤ x ≤ 0.22. The utility of the intermediate phase as a predictor of the material properties in network glass-forming systems is discussed.

High-Dose Radiotherapy With or Without Androgen Deprivation Therapy for Intermediate-Risk Prostate Cancer: Cancer Control and Toxicity Outcomes

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

Edelman, Scott; Liauw, Stanley L.; Rossi, Peter J.

2012-08-01

Purpose: To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). Methods and Materials: Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as {>=}T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: {>=}T3, prostate-specific antigen level >20 ng/mL, GS {>=}8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADTmore » and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. Results: For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. Conclusions: Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy-related GI or GU toxicity.« less

Calcium-Binding Proteins S100A8 and S100A9: Investigation of Their Immune Regulatory Effect in Myeloid Cells.

PubMed

Yang, Jianxin; Anholts, Jacqueline; Kolbe, Ulrike; Stegehuis-Kamp, Janine A; Claas, Frans H J; Eikmans, Michael

2018-06-21

High expression levels of the calcium-binding proteins S100A8 and S100A9 in myeloid cells in kidney transplant rejections are associated with a favorable outcome. Here we investigated the myeloid cell subset expressing these molecules, and their function in inflammatory reactions. Different monocyte subsets were sorted from buffy coats of healthy donors and investigated for S100A8 and S100A9 expression. To characterize S100A9high and S100A9low subsets within the CD14+ classical monocyte subset, intracellular S100A9 staining was combined with flow cytometry (FACS) and qPCR profiling. Furthermore, S100A8 and S100A9 were overexpressed by transfection in primary monocyte-derived macrophages and the THP-1 macrophage cell line to investigate the functional relevance. Expression of S100A8 and S100A9 was primarily found in classical monocytes and to a much lower extent in intermediate and non-classical monocytes. All S100A9+ cells expressed human leukocyte antigen—antigen D related (HLA-DR) on their surface. A small population (<3%) of CD14+ CD11b+ CD33+ HLA-DR− cells, characterized as myeloid derived suppressor cells (MDSCs), also expressed S100A9 to high extent. Overexpression of S100A8 and S00A9 in macrophages led to enhanced extracellular reactive oxygen species (ROS) production, as well as elevated mRNA expression of anti-inflammatory IL-10 . The results suggest that the calcium-binding proteins S100A8 and S100A9 in myeloid cells have an immune regulatory effect.

Functionally distinct roles for different miR-155 expression levels through contrasting effects on gene expression, in acute myeloid leukaemia.

PubMed

Narayan, N; Morenos, L; Phipson, B; Willis, S N; Brumatti, G; Eggers, S; Lalaoui, N; Brown, L M; Kosasih, H J; Bartolo, R C; Zhou, L; Catchpoole, D; Saffery, R; Oshlack, A; Goodall, G J; Ekert, P G

2017-04-01

Enforced expression of microRNA-155 (miR-155) in myeloid cells has been shown to have both oncogenic or tumour-suppressor functions in acute myeloid leukaemia (AML). We sought to resolve these contrasting effects of miR-155 overexpression using murine models of AML and human paediatric AML data sets. We show that the highest miR-155 expression levels inhibited proliferation in murine AML models. Over time, enforced miR-155 expression in AML in vitro and in vivo, however, favours selection of intermediate miR-155 expression levels that results in increased tumour burden in mice, without accelerating the onset of disease. Strikingly, we show that intermediate and high miR-155 expression also regulate very different subsets of miR-155 targets and have contrasting downstream effects on the transcriptional environments of AML cells, including genes involved in haematopoiesis and leukaemia. Furthermore, we show that elevated miR-155 expression detected in paediatric AML correlates with intermediate and not high miR-155 expression identified in our experimental models. These findings collectively describe a novel dose-dependent role for miR-155 in the regulation of AML, which may have important therapeutic implications.

Postinjection single photon transmission tomography with ordered-subset algorithms for whole-body PET imaging

NASA Astrophysics Data System (ADS)

Bai, Chuanyong; Kinahan, P. E.; Brasse, D.; Comtat, C.; Townsend, D. W.

2002-02-01

We have evaluated the penalized ordered-subset transmission reconstruction (OSTR) algorithm for postinjection single photon transmission scanning. The OSTR algorithm of Erdogan and Fessler (1999) uses a more accurate model for transmission tomography than ordered-subsets expectation-maximization (OSEM) when OSEM is applied to the logarithm of the transmission data. The OSTR algorithm is directly applicable to postinjection transmission scanning with a single photon source, as emission contamination from the patient mimics the effect, in the original derivation of OSTR, of random coincidence contamination in a positron source transmission scan. Multiple noise realizations of simulated postinjection transmission data were reconstructed using OSTR, filtered backprojection (FBP), and OSEM algorithms. Due to the nonspecific task performance, or multiple uses, of the transmission image, multiple figures of merit were evaluated, including image noise, contrast, uniformity, and root mean square (rms) error. We show that: 1) the use of a three-dimensional (3-D) regularizing image roughness penalty with OSTR improves the tradeoffs in noise, contrast, and rms error relative to the use of a two-dimensional penalty; 2) OSTR with a 3-D penalty has improved tradeoffs in noise, contrast, and rms error relative to FBP or OSEM; and 3) the use of image standard deviation from a single realization to estimate the true noise can be misleading in the case of OSEM. We conclude that using OSTR with a 3-D penalty potentially allows for shorter postinjection transmission scans in single photon transmission tomography in positron emission tomography (PET) relative to FBP or OSEM reconstructed images with the same noise properties. This combination of singles+OSTR is particularly suitable for whole-body PET oncology imaging.

Type III Cells in Anterior Taste Fields Are More Immunohistochemically Diverse Than Those of Posterior Taste Fields in Mice.

PubMed

Wilson, Courtney E; Finger, Thomas E; Kinnamon, Sue C

2017-10-31

Activation of Type III cells in mammalian taste buds is implicated in the transduction of acids (sour) and salty stimuli. Several lines of evidence suggest that function of Type III cells in the anterior taste fields may differ from that of Type III cells in posterior taste fields. Underlying anatomy to support this observation is, however, scant. Most existing immunohistochemical data characterizing this cell type focus on circumvallate taste buds in the posterior tongue. Equivalent data from anterior taste fields-fungiform papillae and soft palate-are lacking. Here, we compare Type III cells in four taste fields: fungiform, soft palate, circumvallate, and foliate in terms of reactivity to four canonical markers of Type III cells: polycystic kidney disease 2-like 1 (PKD2L1), synaptosomal associated protein 25 (SNAP25), serotonin (5-HT), and glutamate decarboxylase 67 (GAD67). Our findings indicate that while PKD2L1, 5-HT, and SNAP25 are highly coincident in posterior taste fields, they diverge in anterior taste fields. In particular, a subset of taste cells expresses PKD2L1 without the synaptic markers, and a subset of SNAP25 cells lacks expression of PKD2L1. In posterior taste fields, GAD67-positive cells are a subset of PKD2L1 expressing taste cells, but anterior taste fields also contain a significant population of GAD67-only expressing cells. These differences in expression patterns may underlie the observed functional differences between anterior and posterior taste fields. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Validation of American Thyroid Association Ultrasound Risk Assessment of Thyroid Nodules Selected for Ultrasound Fine-Needle Aspiration.

PubMed

Tang, Alice L; Falciglia, Mercedes; Yang, Huaitao; Mark, Jonathan R; Steward, David L

2017-08-01

The aim of this study was to validate the American Thyroid Association (ATA) sonographic risk assessment of thyroid nodules. The ATA sonographic risk assessment was prospectively applied to 206 thyroid nodules selected for ultrasound-guided fine-needle aspiration (US-FNA), and analyzed with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), as well as surgical pathology for the subset undergoing surgical excision. The analysis included 206 thyroid nodules averaging 2.4 cm (range 1-7 cm; standard error of the mean 0.07). Using the ATA US pattern risk assessment, nodules were classified as high (4%), intermediate (31%), low (38%), and very low (26%) risk of malignancy. Nodule size was inversely correlated with sonographic risk assessment, as lower risk nodules were larger on average (p < 0.0001). Malignancy rates determined by cytology/surgical pathology were high 100%, intermediate 11%, low 8%, and very low 2%, which were closely aligned with ATA malignancy risk estimates (high 70-90%, intermediate 10-20%, low 5-10%, and very low 3%). ATA US pattern risk assessment also appropriately predicted the proportion of nodules classified as malignant or suspicious for malignancy through TBSRTC classification-high (77%), intermediate (6%), low (1%), and very low 0%-as well as benign TBSRTC classification-high (0%), intermediate (47%), low (61%), and very low (70%) (p < 0.0001). Malignancy rates of surgically excised, cytologically indeterminate nodules followed ATA sonographic risk stratification (high 100%, intermediate 21%, low 17%, and very low 12%; p = 0.003). This prospective study supports the new ATA sonographic pattern risk assessment for selection of thyroid nodules for US-FNA based upon TBSRTC and surgical pathology results. In the setting of indeterminate cytopathology, nodules categorized as atypia of undetermined significance/follicular lesion of undetermined significance with ATA high-risk sonographic patterns have a high likelihood of being malignant.

Chemokine Receptor Expression on Normal Blood CD56+ NK-Cells Elucidates Cell Partners That Comigrate during the Innate and Adaptive Immune Responses and Identifies a Transitional NK-Cell Population

PubMed Central

Queirós, Maria Luís; Gonçalves, Marta; Fonseca, Sónia; Moura, João

2015-01-01

Studies of chemokine receptors (CKR) in natural killer- (NK-) cells have already been published, but only a few gave detailed information on its differential expression on blood NK-cell subsets. We report on the expression of the inflammatory and homeostatic CKR on normal blood CD56+low CD16+ and CD56+high  CD16−/+low NK-cells. Conventional CD56+low and CD56+high NK-cells present in the normal PB do express CKR for inflammatory cytokines, although with different patterns CD56+low NK-cells are mainly CXCR1/CXCR2+ and CXCR3/CCR5−/+, whereas mostly CD56+high NK-cells are CXCR1/CXCR2− and CXCR3/CCR5+. Both NK-cell subsets have variable CXCR4 expression and are CCR4− and CCR6−. The CKR repertoire of the CD56+low NK-cells approaches to that of neutrophils, whereas the CKR repertoire of the CD56+high NK-cells mimics that of Th1+ T cells, suggesting that these cells are prepared to migrate into inflamed tissues at different phases of the immune response. In addition, we describe a subpopulation of NK-cells with intermediate levels of CD56 expression, which we named CD56+int NK-cells. These NK-cells are CXCR3/CCR5+, they have intermediate levels of expression of CD16, CD62L, CD94, and CD122, and they are CD57− and CD158a−. In view of their phenotypic features, we hypothesize that they correspond to a transitional stage, between the well-known CD56+high and CD56+low NK-cells populations. PMID:26543875

Abnormal intermediate filament organization alters mitochondrial motility in giant axonal neuropathy fibroblasts

PubMed Central

Lowery, Jason; Jain, Nikhil; Kuczmarski, Edward R.; Mahammad, Saleemulla; Goldman, Anne; Gelfand, Vladimir I.; Opal, Puneet; Goldman, Robert D.

2016-01-01

Giant axonal neuropathy (GAN) is a rare disease caused by mutations in the GAN gene, which encodes gigaxonin, an E3 ligase adapter that targets intermediate filament (IF) proteins for degradation in numerous cell types, including neurons and fibroblasts. The cellular hallmark of GAN pathology is the formation of large aggregates and bundles of IFs. In this study, we show that both the distribution and motility of mitochondria are altered in GAN fibroblasts and this is attributable to their association with vimentin IF aggregates and bundles. Transient expression of wild-type gigaxonin in GAN fibroblasts reduces the number of IF aggregates and bundles, restoring mitochondrial motility. Conversely, silencing the expression of gigaxonin in control fibroblasts leads to changes in IF organization similar to that of GAN patient fibroblasts and a coincident loss of mitochondrial motility. The inhibition of mitochondrial motility in GAN fibroblasts is not due to a global inhibition of organelle translocation, as lysosome motility is normal. Our findings demonstrate that it is the pathological changes in IF organization that cause the loss of mitochondrial motility. PMID:26700320

Does Thioflavin-T Detect Oligomers Formed During Amyloid Fibril Assembly

NASA Astrophysics Data System (ADS)

Persichilli, Christopher; Hill, Shannon E.; Mast, Jason; Muschol, Martin

2011-03-01

Recent results have shown that oligomeric intermediates of amyloid fibril assembly represent the main toxic species in disorders such as Alzheimer's disease and type II diabetes. Thioflavin-T (ThT) is among the most commonly used indicator dyes for mature amyloid fibrils in vitro. We used ThT to monitor amyloid fibril formation of lysozyme (HEWL), and correlated ThT fluorescence to concurrent dynamic light scattering and atomic force microscopy measurements. Specifically, we tested the ability of ThT to discern among oligomer-free vs. oligomeric fibril assembly pathways. We found that ThT fluorescence did not detect oligomer growth; however, fluorescence increases did coincide with the formation of monomeric filaments in the oligomer-free assembly pathway. This implies that ThT fluorescence is not generally suitable for the detection of oligomeric intermediates. The results further suggest different internal structures for oligomeric vs. monomeric filaments. This research was supported, in part, by funding through the Byrd Alzheimer's Institute (ARG-2007-22) and the BITT-Florida Center of Excellence for M.M., an NSF-REU grant (DMR-1004873) for C. P. and an NSF-IGERT fellowship for S.H.

Studies of a Next-Generation Silicon-Photomultiplier-Based Time-of-Flight PET/CT System.

PubMed

Hsu, David F C; Ilan, Ezgi; Peterson, William T; Uribe, Jorge; Lubberink, Mark; Levin, Craig S

2017-09-01

This article presents system performance studies for the Discovery MI PET/CT system, a new time-of-flight system based on silicon photomultipliers. System performance and clinical imaging were compared between this next-generation system and other commercially available PET/CT and PET/MR systems, as well as between different reconstruction algorithms. Methods: Spatial resolution, sensitivity, noise-equivalent counting rate, scatter fraction, counting rate accuracy, and image quality were characterized with the National Electrical Manufacturers Association NU-2 2012 standards. Energy resolution and coincidence time resolution were measured. Tests were conducted independently on two Discovery MI scanners installed at Stanford University and Uppsala University, and the results were averaged. Back-to-back patient scans were also performed between the Discovery MI, Discovery 690 PET/CT, and SIGNA PET/MR systems. Clinical images were reconstructed using both ordered-subset expectation maximization and Q.Clear (block-sequential regularized expectation maximization with point-spread function modeling) and were examined qualitatively. Results: The averaged full widths at half maximum (FWHMs) of the radial/tangential/axial spatial resolution reconstructed with filtered backprojection at 1, 10, and 20 cm from the system center were, respectively, 4.10/4.19/4.48 mm, 5.47/4.49/6.01 mm, and 7.53/4.90/6.10 mm. The averaged sensitivity was 13.7 cps/kBq at the center of the field of view. The averaged peak noise-equivalent counting rate was 193.4 kcps at 21.9 kBq/mL, with a scatter fraction of 40.6%. The averaged contrast recovery coefficients for the image-quality phantom were 53.7, 64.0, 73.1, 82.7, 86.8, and 90.7 for the 10-, 13-, 17-, 22-, 28-, and 37-mm-diameter spheres, respectively. The average photopeak energy resolution was 9.40% FWHM, and the average coincidence time resolution was 375.4 ps FWHM. Clinical image comparisons between the PET/CT systems demonstrated the high quality of the Discovery MI. Comparisons between the Discovery MI and SIGNA showed a similar spatial resolution and overall imaging performance. Lastly, the results indicated significantly enhanced image quality and contrast-to-noise performance for Q.Clear, compared with ordered-subset expectation maximization. Conclusion: Excellent performance was achieved with the Discovery MI, including 375 ps FWHM coincidence time resolution and sensitivity of 14 cps/kBq. Comparisons between reconstruction algorithms and other multimodal silicon photomultiplier and non-silicon photomultiplier PET detector system designs indicated that performance can be substantially enhanced with this next-generation system. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Interactions between spontaneous instantiations to the basic level and post-event suggestions.

PubMed

Pansky, Ainat; Tenenboim, Einat

2011-11-01

Extensive research shows that post-event suggestions can distort the memory for a target event. In this study we examined the effect of such suggestions as they interact with the products of a spontaneous memory process: instantiation of abstract information to an intermediate level of abstractness, the basic level (Pansky & Koriat, 2004 ). Participants read a narrative containing items presented at the superordinate level (e.g., FRUIT), were exposed to suggestions that referred to these items at the basic level (e.g., APPLE), and were finally asked to recall the original items. We found that the tendency to instantiate spontaneously in the control (non-misleading) condition, particularly over time, increased following exposure to suggestions that were likely to coincide with those instantiations. Exposure to such suggestions, either immediately or following a 24-hour delay, reduced subsequent correct recall of the original items only if the suggested information coincided with the information one tends to instantiate spontaneously in a given context. Suggestibility, in this case, was particularly pronounced and phenomenologically compelling in terms of remember/know judgements. The findings are taken to imply that effects of post-event suggestions can be understood in terms of the constructive processes that set the stage for their occurrence.

H2 as a Possible Carrier of the DIBs?

NASA Astrophysics Data System (ADS)

Ubachs, W.

2014-02-01

In the 1990s the hydrogen molecule, by far the most abundant molecular species in the interstellar medium, has been proposed as a possible carrier of the diffuse interstellar bands. While some remarkable coincidences were found in the rich spectrum of inter-Rydberg transitions of this molecule with DIB-features, both in frequency position as in linewidth, some open issues remained on a required non-linear optical pumping scheme that should explain the population of certain intermediate levels and act as a selection mechanism. Recently a similar scheme has been proposed relating the occurrence of the UV-bump (the ubiquitous 2170 Å extinction feature) to the spectrum of H2, therewith reviving the H2 hypothesis.

Differential adipokine receptor expression on circulating leukocyte subsets in lean and obese children.

PubMed

Keustermans, Genoveva; van der Heijden, Laila B; Boer, Berlinda; Scholman, Rianne; Nuboer, Roos; Pasterkamp, Gerard; Prakken, Berent; de Jager, Wilco; Kalkhoven, Eric; Janse, Arieke J; Schipper, Henk S

2017-01-01

Childhood obesity prevalence has increased worldwide and is an important risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). The production of inflammatory adipokines by obese adipose tissue contributes to the development of T2D and CVD. While levels of circulating adipokines such as adiponectin and leptin have been established in obese children and adults, the expression of adiponectin and leptin receptors on circulating immune cells can modulate adipokine signalling, but has not been studied so far. Here, we aim to establish the expression of adiponectin and leptin receptors on circulating immune cells in obese children pre and post-lifestyle intervention compared to normal weight control children. 13 obese children before and after a 1-year lifestyle intervention were compared with an age and sex-matched normal weight control group of 15 children. Next to routine clinical and biochemical parameters, circulating adipokines were measured, and flow cytometric analysis of adiponectin receptor 1 and 2 (AdipoR1, AdipoR2) and leptin receptor expression on peripheral blood mononuclear cell subsets was performed. Obese children exhibited typical clinical and biochemical characteristics compared to controls, including a higher BMI-SD, blood pressure and circulating leptin levels, combined with a lower insulin sensitivity index (QUICKI). The 1-year lifestyle intervention resulted in stabilization of their BMI-SD. Overall, circulating leukocyte subsets showed distinct adipokine receptor expression profiles. While monocytes expressed high levels of all adipokine receptors, NK and iNKT cells predominantly expressed AdipoR2, and B-lymphocytes and CD4+ and CD8+ T-lymphocyte subsets expressed AdipoR2 as well as leptin receptor. Strikingly though, leukocyte subset numbers and adipokine receptor expression profiles were largely similar in obese children and controls. Obese children showed higher naïve B-cell numbers, and pre-intervention also higher numbers of immature transition B-cells and intermediate CD14++CD16+ monocytes combined with lower total monocyte numbers, compared to controls. Furthermore, adiponectin receptor 1 expression on nonclassical CD14+CD16++ monocytes was consistently upregulated in obese children pre-intervention, compared to controls. However, none of the differences in leukocyte subset numbers and adipokine receptor expression profiles between obese children and controls remained significant after multiple testing correction. First, the distinct adipokine receptor profiles of circulating leukocyte subsets may partly explain the differential impact of adipokines on leukocyte subsets. Second, the similarities in adipokine receptor expression profiles between obese children and normal weight controls suggest that adipokine signaling in childhood obesity is primarily modulated by circulating adipokine levels, instead of adipokine receptor expression.

Timing of Benthic Foraminiferal δ18O Change in Deep and Intermediate Waters of the Atlantic and Indo-Pacific for 0-45 ka

NASA Astrophysics Data System (ADS)

Stern, J.; Lisiecki, L. E.

2011-12-01

Isotopic and compositional studies of marine sediment cores provide a wealth of insight into past and present climate processes, but accurately dating these records remains problematic. Age models developed by correlation of marine isotope stages in benthic foraminiferal δ18O are limited by the degree to which similarity in the timing and character of the records can be assumed. Skinner and Shackleton (2005) demonstrated that the marine isotope stage (MIS) 2/1 boundary in benthic foraminiferal δ18O occurred ~4,000 yr later at a deep equatorial Pacific site compared to a deep North Atlantic site due to diachronous changes in deep water temperature and local hydrography during the deglaciation. To further investigate the extent of potential differences at both orbital and millennial timescales, we compare stacks of benthic foraminiferal δ18O for the intermediate Atlantic, deep Atlantic, intermediate Indo-Pacific, and deep Indo-Pacific. The four stacks were generated by averaging together 40, 153, 30, and 75 individual records, respectively. Unique age models for each of the four stacks from 0-45 ka are based on a total of >1,200 radiocarbon dates from planktonic foraminfera in a subset of the cores used for the stacks. We discuss the relative timing of major events during Termination I in the four stacks, including a prominent reversal ~13-15 ka in the intermediate Atlantic. We also compare the expression of millennial-scale climate change associated with Heinrich Event 4 in the four stacks.

Ebola Virus Disease Is Characterized by Poor Activation and Reduced Levels of Circulating CD16+ Monocytes.

PubMed

Lüdtke, Anja; Ruibal, Paula; Becker-Ziaja, Beate; Rottstegge, Monika; Wozniak, David M; Cabeza-Cabrerizo, Mar; Thorenz, Anja; Weller, Romy; Kerber, Romy; Idoyaga, Juliana; Magassouba, N'Faly; Gabriel, Martin; Günther, Stephan; Oestereich, Lisa; Muñoz-Fontela, César

2016-10-15

A number of previous studies have identified antigen-presenting cells (APCs) as key targets of Ebola virus (EBOV), but the role of APCs in human Ebola virus disease (EVD) is not known. We have evaluated the phenotype and kinetics of monocytes, neutrophils, and dendritic cells (DCs) in peripheral blood of patients for whom EVD was diagnosed by the European Mobile Laboratory in Guinea. Acute EVD was characterized by reduced levels of circulating nonclassical CD16 + monocytes with a poor activation profile. In survivors, CD16 + monocytes were activated during recovery, coincident with viral clearance, suggesting an important role of this cell subset in EVD pathophysiology. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Geochemical and sedimentological records of intermediate-depth circulation in the Labrador Sea since the Last Glacial Maximum

NASA Astrophysics Data System (ADS)

Hoffmann, S. S.; Dalsing, R.; McManus, J. F.

2016-12-01

Dynamical sedimentary proxies for deep ocean circulation, such as mean sortable silt size and 231Pa/230Th, allow the reconstruction of past changes in deep water circulation speed and ocean basin ventilation. This provides an important addition to traditional methods of deep water circulation reconstruction such as mapping water mass geometry through foraminiferal carbon isotopic records. We have produced records of mean sortable silt size from three intermediate-depth sediment core sites in the Labrador Sea, taken from the continental slope and Orphan Knoll east of Newfoundland, to reconstruct changes in intermediate depth water circulation including Glacial North Atlantic Intermediate Water and Labrador Sea Water. Radiocarbon dating indicates that the cores span the Holocene, deglaciation and LGM. Increases in mean sortable silt size appear to coincide with Heinrich Event 1, the Older Dryas, Younger Dryas, and mid-late Holocene, which could suggest increased bottom current speeds at these times. However, ice-rafted debris contributes to marine sediments in this region, and mean sortable silt size at times of major IRD input such as Heinrich Event 1 may therefore reflect multiple influences. We will use inverse modeling techniques to determine likely end members contributing to the sortable silt fraction and to correct for the effect of IRD on sortable silt size, allowing a better understanding of the influence of current speed on these samples. We combine these sortable silt measurements with the sedimentary geochemical proxy 231Pa/230Th, which has been used to reconstruct changes in North Atlantic meridional overturning circulation. New 231Pa/230Th data from cores KN158-4-27/28, which provided our best-resolved sortable silt record, will allow us to compare results from the two dynamical proxies to better understand both the behavior of these proxies in the Labrador Sea, and the history of intermediate-depth circulation and ventilation in the Labrador Sea during major abrupt climate events and transitions.

Calculated and perceived cardiovascular risk in asymptomatic subjects submitted to a routine medical evaluation: The perception gap.

PubMed

Katz, Marcelo; Laurinavicius, Antonio G; Franco, Fabio G M; Conceicao, Raquel D; Carvalho, Jose A M; Pesaro, Antonio E P; Wajngarten, Mauricio; Santos, Raul D

2015-08-01

Poor adherence to medical treatment represents a major health problem. A subject's misperception of his own cardiovascular risk has been indicated as a key driver for low compliance with preventive measures. This study analysed the relationship between objectively calculated short- and long-term cardiovascular risk and its subjective perception. Cross-sectional study in asymptomatic Brazilian subjects. Individuals (N = 6544, mean age 49.1 ± 7 years, 22.2% female) who underwent a routine mandatory health evaluation were studied. A questionnaire in which each individual rated his own cardiovascular risk as low, intermediate or high according to his own perception was used. The 10-year and lifetime cardiovascular risk were calculated respectively using the Framingham risk (FRS) and Lifetime risk (LRS) scores. Individuals were classified as hypo-perceivers (i.e. perceived risk lower than estimated risk), normo-perceivers (i.e. perceived risk coincident with estimated risk) and hyper-perceivers (i.e. perceived risk higher than estimated risk). Cardiovascular risk, using the FRS, was low in 77.9% (N = 5071), intermediate in 14.4% (N = 939) and high in 7.7% (N = 499) of subjects. Cardiovascular risk, using the LRS, was low in 7.6% (N = 492), intermediate in 43.1% (N = 2787) and high in 49.3% (N = 3184) of the study population. The prevalence of normo-perceivers was 57.6% using the FRS and only 20.6% using the LRS. Using the LRS, 72.3% of the intermediate and 91.2% of the high-risk subjects were hypo-perceivers. In a large sample of asymptomatic individuals, there was a gap between calculated and perceived cardiovascular risk. Using a long-term risk score, most of the intermediate- and high-risk subjects were hypo-perceivers. © The European Society of Cardiology 2014.

Direct observation of surface ethyl to ethane interconversion upon C2H4 hydrogenation over Pt/Al2O3 catalyst by time-resolved FT-IR spectroscopy.

PubMed

Wasylenko, Walter; Frei, Heinz

2005-09-08

Time-resolved FT-IR spectra of ethylene hydrogenation over alumina-supported Pt catalyst were recorded at 25 ms resolution in the temperature range of 323-473 K using various H2 concentrations (1 atm total gas pressure). Surface ethyl species (2870 and 1200 cm(-1)) were detected at all temperatures along with the gas-phase ethane product (2954 and 2893 cm(-1)). The CH3CH2Pt growth was instantaneous on the time scale of 25 ms under all experimental conditions. At 323 K, the decay time of surface ethyl (122 +/- 10 ms) coincides with the rise time of ethane (144 +/- 14 ms). This establishes direct kinetic evidence for surface ethyl as the relevant reaction intermediate. Such a direct link between the temporal behavior of an unstable surface intermediate and the final product in a heterogeneous catalytic system has not been demonstrated before. A fraction (25%) of the asymptotic ethane growth at 323 K is prompt, indicating that there are surface ethyl species that react much faster than the majority of the CH3CH2Pt intermediates. The dispersive kinetics is attributed to the varying strength of interaction of the ethyl species with the Pt surface caused by heterogeneity of the surface environment. At 473 K, the majority of ethyl intermediates are hydrogenated prior to the recording of the first time slice (24 ms), and a correspondingly large prompt growth of ethane is observed. The yield and kinetics of the surface ethylidyne are in agreement with the known spectator nature of this species.

Late Quaternary changes in intermediate water oxygenation and oxygen minimum zone, northern Japan: A benthic foraminiferal perspective

NASA Astrophysics Data System (ADS)

Shibahara, Akihiko; Ohkushi, Ken'ichi; Kennett, James P.; Ikehara, Ken

2007-09-01

A strong oxygen minimum zone (OMZ) currently exists at upper intermediate water depths on the northern Japanese margin, NW Pacific. The OMZ results largely from a combination of high surface water productivity and poor ventilation of upper intermediate waters. We investigated late Quaternary history (last 34 kyr) of ocean floor oxygenation and the OMZ using quantitative changes in benthic foraminiferal assemblages in three sediment cores taken from the continental slope off Shimokita Peninsula and Tokachi, northern Japan, at water depths between 975 and 1363 m. These cores are well located within the present-day OMZ, a region of high surface water productivity, and in close proximity to the source region of North Pacific Intermediate Water. Late Quaternary benthic foraminiferal assemblages experienced major changes in response to changes in dissolved oxygen concentration in ocean floor sediments. Foraminiferal assemblages are interpreted to represent three main groups representing oxic, suboxic, and dysoxic conditions. Assemblage changes in all three cores and hence in bottom water oxygenation coincided with late Quaternary climatic episodes, similar to that known for the southern California margin. These episodes, in turn, are correlated with orbital and millennial climate episodes in the Greenland ice core including the last glacial episode, Bølling-Ållerød (B/A), Younger Dryas, Preboreal (earliest Holocene), early Holocene, and late Holocene. The lowest oxygen conditions, marked by dysoxic taxa and laminated sediments in one core, occurred during the B/A and the Preboreal intervals. Suboxic taxa dominated mainly during the last glacial, the Younger Dryas, and most of the Holocene. Dysoxic conditions during the B/A and Preboreal intervals in this region were possibly caused by high surface water productivity at times of reduced intermediate ventilation in the northwestern Pacific. Remarkable similarities are evident in the late Quaternary sequence of benthic foraminiferal assemblage change between the two very distant continental margins of northern Japan and southern California. The oscillations in OMZ strength, reflected by these faunal changes, were widespread and apparently synchronous over wide areas of the North Pacific, reflecting broad changes in intermediate water ventilation and surface ocean productivity closely linked with late Quaternary climate change on millennial and orbital timescales.

A see-saw of pre-Columbian boom regions in southern Peru, determined by large-scale circulation changes

NASA Astrophysics Data System (ADS)

Mächtle, B.; Schittek, K.; Forbriger, M.; Schäbitz, F.; Eitel, B.

2012-04-01

Environmental changes and cultural transitions during several periods of Peruvian history show a strong coincidence between humid and dry climatic oscillations and the rise and decline of cultures. It is noteworthy, that alternating periods of geo-ecological fragility and stability occurred in time and space between the coastal Nasca region (14.5° S) and the high Andean northern Titicaca basin, just a few hundred kilometers to the east. Based on a multi-proxy palynological and sedimentological approach to reconstruct palaeoenvironmental changes, we found that the Nasca region received a maximum of precipitation during the archaeological boom times of the Early Horizon and the Early Intermediate Period (800 BC - 650 AD, Paracas and Nasca cultures) as well as during the late intermediate period (1150-1450 AD), whereas, in contrast, the Titicaca region further to the south-east experienced drought and cultural depression during that times. During the Middle Horizon (650 - 1150 AD), the Tiwanaku agronomy and culture boomed in the Titicaca region and expanded to the west, contemporaneous with a raised lake level and more humid conditions. In the Nasca region, runoff for irrigation purposes was reduced and less reliable due to drought. Considering a coincidence between environmental and cultural changes, we state that success and decline of civilizations were controlled by hydrological oscillations, triggering fertility as well as a critical loss of natural resources. In response to spatial changing resources, cultural foci were shifted. Therefore, the success of pre-Columbian civilizations was closely coupled to areas of geo-ecological favorability, which were directly controlled by distinct regional impacts of large-scale circulation mechanisms, including El Niño - Southern Oscillation (ENSO). Changes in the position of the intertropical convergence zone (ITCZ) and the Bolivian anticyclone determined meridional shifts in moisture transport across the Andes, which directly triggered human migration to the respective granaries.

Solid-Phase Fe Speciation along the Vertical Redox Gradients in Floodplains using XAS and Mössbauer Spectroscopies.

PubMed

Chen, Chunmei; Kukkadapu, Ravi K; Lazareva, Olesya; Sparks, Donald L

2017-07-18

Properties of Fe minerals are poorly understood in natural soils and sediments with variable redox conditions. In this study, we combined 57 Fe Mössbauer and Fe K-edge X-ray absorption spectroscopic (XAS) techniques to assess solid-phase Fe speciation along the vertical redox gradients of floodplains, which exhibited a succession of oxic, anoxic, and suboxic-oxic zones with increasing depth along the vertical profiles. The incised stream channel is bounded on the east by a narrow floodplain and a steep hillslope, and on the west by a broad floodplain. In the eastern floodplain, the anoxic conditions at the intermediate horizon (55-80 cm) coincided with lower Fe(III)-oxides (particularly ferrihydrite), in concurrence with a greater reduction of phyllosilicates(PS)-Fe(III) to PS-Fe(II), relative to the oxic near-surface and sandy gravel layers. In addition, the anoxic conditions in the eastern floodplain coincided with increased crystallinity of goethite, relative to the oxic layers. In the most reduced intermediate sediments at 80-120 cm of the western floodplain, no Fe(III)-oxides were detected, concurrent with the greatest PS-Fe(III) reduction (PS-Fe(II)/Fe(III) ratio ≈ 1.2 (Mössbauer) or 0.8 (XAS)). In both oxic near-surface horizon and oxic-suboxic gravel aquifers beneath the soil horizons, Fe(III)-oxides were mainly present as ferrihydrite with a much less amount of goethite, which preferentially occurred as nanogoethite or Al/Si-substituted goethite. Ferrihydrite with varying crystallinity or impurities such as organic matter, Al or Si, persisted under suboxic-oxic conditions in the floodplain. This study indicates that vertical redox gradients exert a major control on the quantity and speciation of Fe(III) oxides as well as the oxidation state of structural Fe in PS, which could significantly affect nutrient cycling and carbon (de)stabilization.

Crossover behavior of the thermal conductance and Kramers’ transition rate theory

DOE PAGES

Velizhanin, Kirill A.; Sahu, Subin; Chien, Chih -Chun; ...

2015-12-04

Kramers’ theory frames chemical reaction rates in solution as reactants overcoming a barrier in the presence of friction and noise. For weak coupling to the solution, the reaction rate is limited by the rate at which the solution can restore equilibrium after a subset of reactants have surmounted the barrier to become products. For strong coupling, there are always sufficiently energetic reactants. However, the solution returns many of the intermediate states back to the reactants before the product fully forms. Here, we demonstrate that the thermal conductance displays an analogous physical response to the friction and noise that drive themore » heat current through a material or structure. A crossover behavior emerges where the thermal reservoirs dominate the conductance at the extremes and only in the intermediate region are the intrinsic properties of the lattice manifest. Finally, not only does this shed new light on Kramers’ classic turnover problem, this result is significant for the design of devices for thermal management and other applications, as well as the proper simulation of transport at the nanoscale.« less

Daptomycin non-susceptibility in vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous-VISA (hVISA): implications for therapy after vancomycin treatment failure.

PubMed

Kelley, Peter G; Gao, Wei; Ward, Peter B; Howden, Benjamin P

2011-05-01

The aim of this study was to establish the relationship between reduced vancomycin and daptomycin susceptibility among Australasian vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous-VISA (hVISA) isolates from patients never exposed to daptomycin. Forty-seven stored clinical isolates of hVISA/VISA collected before November 2008 from around Australia and New Zealand were selected. Daptomycin and vancomycin MIC testing was performed using broth microdilution (BMD) and Etest methods. Daptomycin population analysis was performed on a subset of isolates. The percentage of daptomycin non-susceptible isolates was 0% for vancomycin-susceptible S. aureus (VSSA) (Etest and BMD), for hVISA it was 26% by Etest and 15% by BMD, and for VISA 62% by Etest and 38% by BMD. Population analysis profile testing demonstrated daptomycin heteroresistance among the hVISA and VISA strains tested. This is the highest rate of daptomycin non-susceptibility reported among hVISA isolates to date. Clinicians should exhibit caution when using daptomycin in situations where serious hVISA or VISA infection is a possibility.

Mitochondrial transcription terminator family members mTTF and mTerf5 have opposing roles in coordination of mtDNA synthesis.

PubMed

Jõers, Priit; Lewis, Samantha C; Fukuoh, Atsushi; Parhiala, Mikael; Ellilä, Simo; Holt, Ian J; Jacobs, Howard T

2013-01-01

All genomes require a system for avoidance or handling of collisions between the machineries of DNA replication and transcription. We have investigated the roles in this process of the mTERF (mitochondrial transcription termination factor) family members mTTF and mTerf5 in Drosophila melanogaster. The two mTTF binding sites in Drosophila mtDNA, which also bind mTerf5, were found to coincide with major sites of replication pausing. RNAi-mediated knockdown of either factor resulted in mtDNA depletion and developmental arrest. mTTF knockdown decreased site-specific replication pausing, but led to an increase in replication stalling and fork regression in broad zones around each mTTF binding site. Lagging-strand DNA synthesis was impaired, with extended RNA/DNA hybrid segments seen in replication intermediates. This was accompanied by the accumulation of recombination intermediates and nicked/broken mtDNA species. Conversely, mTerf5 knockdown led to enhanced replication pausing at mTTF binding sites, a decrease in fragile replication intermediates containing single-stranded segments, and the disappearance of species containing segments of RNA/DNA hybrid. These findings indicate an essential and previously undescribed role for proteins of the mTERF family in the integration of transcription and DNA replication, preventing unregulated collisions and facilitating productive interactions between the two machineries that are inferred to be essential for completion of lagging-strand DNA synthesis.

Mitochondrial Transcription Terminator Family Members mTTF and mTerf5 Have Opposing Roles in Coordination of mtDNA Synthesis

PubMed Central

Jõers, Priit; Lewis, Samantha C.; Fukuoh, Atsushi; Parhiala, Mikael; Ellilä, Simo; Holt, Ian J.; Jacobs, Howard T.

2013-01-01

All genomes require a system for avoidance or handling of collisions between the machineries of DNA replication and transcription. We have investigated the roles in this process of the mTERF (mitochondrial transcription termination factor) family members mTTF and mTerf5 in Drosophila melanogaster. The two mTTF binding sites in Drosophila mtDNA, which also bind mTerf5, were found to coincide with major sites of replication pausing. RNAi-mediated knockdown of either factor resulted in mtDNA depletion and developmental arrest. mTTF knockdown decreased site-specific replication pausing, but led to an increase in replication stalling and fork regression in broad zones around each mTTF binding site. Lagging-strand DNA synthesis was impaired, with extended RNA/DNA hybrid segments seen in replication intermediates. This was accompanied by the accumulation of recombination intermediates and nicked/broken mtDNA species. Conversely, mTerf5 knockdown led to enhanced replication pausing at mTTF binding sites, a decrease in fragile replication intermediates containing single-stranded segments, and the disappearance of species containing segments of RNA/DNA hybrid. These findings indicate an essential and previously undescribed role for proteins of the mTERF family in the integration of transcription and DNA replication, preventing unregulated collisions and facilitating productive interactions between the two machineries that are inferred to be essential for completion of lagging-strand DNA synthesis. PMID:24068965

Intermediate Pond Sizes Contain the Highest Density, Richness, and Diversity of Pond-Breeding Amphibians

PubMed Central

Semlitsch, Raymond D.; Peterman, William E.; Anderson, Thomas L.; Drake, Dana L.; Ousterhout, Brittany H.

2015-01-01

We present data on amphibian density, species richness, and diversity from a 7140-ha area consisting of 200 ponds in the Midwestern U.S. that represents most of the possible lentic aquatic breeding habitats common in this region. Our study includes all possible breeding sites with natural and anthropogenic disturbance processes that can be missing from studies where sampling intensity is low, sample area is small, or partial disturbance gradients are sampled. We tested whether pond area was a significant predictor of density, species richness, and diversity of amphibians and if values peaked at intermediate pond areas. We found that in all cases a quadratic model fit our data significantly better than a linear model. Because small ponds have a high probability of pond drying and large ponds have a high probability of fish colonization and accumulation of invertebrate predators, drying and predation may be two mechanisms driving the peak of density and diversity towards intermediate values of pond size. We also found that not all intermediate sized ponds produced many larvae; in fact, some had low amphibian density, richness, and diversity. Further analyses of the subset of ponds represented in the peak of the area distribution showed that fish, hydroperiod, invertebrate density, and canopy are additional factors that drive density, richness and diversity of ponds up or down, when extremely small or large ponds are eliminated. Our results indicate that fishless ponds at intermediate sizes are more diverse, produce more larvae, and have greater potential to recruit juveniles into adult populations of most species sampled. Further, hylid and chorus frogs are found predictably more often in ephemeral ponds whereas bullfrogs, green frogs, and cricket frogs are found most often in permanent ponds with fish. Our data increase understanding of what factors structure and maintain amphibian diversity across large landscapes. PMID:25906355

Nanomagnetic Droplets and Implications to Orbital Ordering in La1-xSrxCoO3

NASA Astrophysics Data System (ADS)

Phelan, D.; Louca, Despina; Rosenkranz, S.; Lee, S.-H.; Qiu, Y.; Chupas, P. J.; Osborn, R.; Zheng, H.; Mitchell, J. F.; Copley, J. R. D.; Sarrao, J. L.; Moritomo, Y.

2006-01-01

Inelastic cold-neutron scattering on LaCoO3 provided evidence for a distinct low energy excitation at 0.6 meV coincident with the thermally induced magnetic transition. Coexisting strong ferromagnetic (FM) and weaker antiferromagnetic correlations that are dynamic follow the activation to the excited state, identified as the intermediate S=1 spin triplet. This is indicative of dynamical orbital ordering favoring the observed magnetic interactions. With hole doping as in La1-xSrxCoO3, the FM correlations between Co spins become static and isotropically distributed due to the formation of FM droplets. The correlation length and condensation temperature of these droplets increase rapidly with metallicity due to the double exchange mechanism.

Delocalization via Sliding in Solid 4He: Is It Plausible?

NASA Astrophysics Data System (ADS)

Krainyukova, N. V.

2010-02-01

The modified Debye approach was used to calculate the Gibbs free energy for solid 4He and energetic profiles for different atomic displacements with respect to an equilibrium lattice. Atoms interact via the applied Aziz potential. We have found that individual atomic displacements may hardly give rise to any delocalization because of huge barriers but cooperative plane sliding is highly plausible especially in the intermediate phase, which was found to be more favorable than hcp for small cluster sizes. In the latter case the roughness of the potential profile is less than one kelvin. In some particular sliding cases the energy levels in the nearest wells nearly coincide that is a well-known precursor for the delocalization effect.

Low-lying structure and shape evolution in neutron-rich Se isotopes

NASA Astrophysics Data System (ADS)

Chen, S.; Doornenbal, P.; Obertelli, A.; Rodríguez, T. R.; Authelet, G.; Baba, H.; Calvet, D.; Château, F.; Corsi, A.; Delbart, A.; Gheller, J.-M.; Giganon, A.; Gillibert, A.; Lapoux, V.; Motobayashi, T.; Niikura, M.; Paul, N.; Roussé, J.-Y.; Sakurai, H.; Santamaria, C.; Steppenbeck, D.; Taniuchi, R.; Uesaka, T.; Ando, T.; Arici, T.; Blazhev, A.; Browne, F.; Bruce, A. M.; Caroll, R.; Chung, L. X.; Cortés, M. L.; Dewald, M.; Ding, B.; Flavigny, F.; Franchoo, S.; Górska, M.; Gottardo, A.; Jungclaus, A.; Lee, J.; Lettmann, M.; Linh, B. D.; Liu, J.; Liu, Z.; Lizarazo, C.; Momiyama, S.; Moschner, K.; Nagamine, S.; Nakatsuka, N.; Nita, C. R.; Nobs, C.; Olivier, L.; Orlandi, R.; Patel, Z.; Podolyak, Zs.; Rudigier, M.; Saito, T.; Shand, C.; Söderström, P.-A.; Stefan, I.; Vaquero, V.; Werner, V.; Wimmer, K.; Xu, Z.

2017-04-01

Neutron-rich 88,90,92,94Se isotopes were studied via in-beam γ -ray spectroscopy after nucleon removal reactions at intermediate energies at the Radioactive Isotope Beam Factory. Based on γ -γ coincidence analysis, low-lying excitation level schemes are proposed for these nuclei, including the 21+, 41+ states and 22+ states at remarkably low energies. The low-lying 22+ states, along with other features, indicate triaxiality in these nuclei. The experimental results are in good overall agreement with self-consistent beyond-mean-field calculations based on the Gogny D1S interaction, which suggests both triaxial degree of freedom and shape coexistence playing important roles in the description of intrinsic deformations in neutron-rich Se isotopes.

[Evolution of genomic imprinting in mammals: what a zoo!].

PubMed

Proudhon, Charlotte; Bourc'his, Déborah

2010-05-01

Genomic imprinting imposes an obligate mode of biparental reproduction in mammals. This phenomenon results from the monoparental expression of a subset of genes. This specific gene regulation mechanism affects viviparous mammals, especially eutherians, but also marsupials to a lesser extent. Oviparous mammals, or monotremes, do not seem to demonstrate monoparental allele expression. This phylogenic confinement suggests that the evolution of the placenta imposed a selective pressure for the emergence of genomic imprinting. This physiological argument is now complemented by recent genomic evidence facilitated by the sequencing of the platypus genome, a rare modern day case of a monotreme. Analysis of the platypus genome in comparison to eutherian genomes shows a chronological and functional coincidence between the appearance of genomic imprinting and transposable element accumulation. The systematic comparative analyses of genomic sequences in different species is essential for the further understanding of genomic imprinting emergence and divergent evolution along mammalian speciation.

Curvature and gravity actions for matrix models: II. The case of general Poisson structures

NASA Astrophysics Data System (ADS)

Blaschke, Daniel N.; Steinacker, Harold

2010-12-01

We study the geometrical meaning of higher order terms in matrix models of Yang-Mills type in the semi-classical limit, generalizing recent results (Blaschke and Steinacker 2010 Class. Quantum Grav. 27 165010 (arXiv:1003.4132)) to the case of four-dimensional spacetime geometries with general Poisson structure. Such terms are expected to arise e.g. upon quantization of the IKKT-type models. We identify terms which depend only on the intrinsic geometry and curvature, including modified versions of the Einstein-Hilbert action as well as terms which depend on the extrinsic curvature. Furthermore, a mechanism is found which implies that the effective metric G on the spacetime brane {\\cal M}\\subset \\mathds{R}^D 'almost' coincides with the induced metric g. Deviations from G = g are suppressed, and characterized by the would-be U(1) gauge field.

The Southern HII Region Discovery Survey: Preliminary Results

NASA Astrophysics Data System (ADS)

Shea, Jeanine; Wenger, Trey; Balser, Dana S.; Anderson, Loren D.; Armentrout, William P.; Bania, Thomas M.; Dawson, Joanne; Miller Dickey, John; Jordan, Christopher; McClure-Griffiths, Naomi M.

2017-01-01

HII regions are some of the brightest sources at radio frequencies in the Milky Way and are the sites of massive O and B-type star formation. They have relatively short (< 10 Myr) lifetimes compared to other Galactic objects and therefore reveal information about spiral structure and the chemical evolution of the Galaxy. The HII Region Discovery Surveys (HRDS) discovered about 800 new HII regions in the Galactic longitude range -20 degrees to 270 degrees using primarily the Green Bank Telescope. Candidate HII regions were selected from mid-infrared emission coincident with radio continuum emission, and confirmed as HII regions by the detection of radio recombination lines. Here we discuss the Southern HII Region Discovery Survey (SHRDS), a continuation of the HRDS using the Australia Telescope Compact Array over the Galactic longitude range 230 to 360 degrees. We have reduced and analyzed a small sub-set of the SHRDS sources and discuss preliminary results, including kinematic distances and metallicities.

Activation of cellular death programs associated with immunosenescence-like phenotype in TPPII knockout mice

PubMed Central

Huai, Jisen; Firat, Elke; Nil, Ahmed; Million, Daniele; Gaedicke, Simone; Kanzler, Benoit; Freudenberg, Marina; van Endert, Peter; Kohler, Gabriele; Pahl, Heike L.; Aichele, Peter; Eichmann, Klaus; Niedermann, Gabriele

2008-01-01

The giant cytosolic protease tripeptidyl peptidase II (TPPII) has been implicated in the regulation of proliferation and survival of malignant cells, particularly lymphoma cells. To address its functions in normal cellular and systemic physiology we have generated TPPII-deficient mice. TPPII deficiency activates cell type-specific death programs, including proliferative apoptosis in several T lineage subsets and premature cellular senescence in fibroblasts and CD8+ T cells. This coincides with up-regulation of p53 and dysregulation of NF-κB. Prominent degenerative alterations at the organismic level were a decreased lifespan and symptoms characteristic of immunohematopoietic senescence. These symptoms include accelerated thymic involution, lymphopenia, impaired proliferative T cell responses, extramedullary hematopoiesis, and inflammation. Thus, TPPII is important for maintaining normal cellular and systemic physiology, which may be relevant for potential therapeutic applications of TPPII inhibitors. PMID:18362329

La Freccia Rossa: an IR-dark cloud hosting the Milky Way intermediate-mass black hole candidate

NASA Astrophysics Data System (ADS)

Ravi, Vikram; Vedantham, Harish; Phinney, E. Sterl

2018-07-01

The dynamics of the high-velocity compact molecular cloud CO-0.40-0.22 have been interpreted as evidence for a ˜105 M⊙ black hole within 60 pc of Sgr A*. Recently, Oka et al. have identified a compact millimetre-continuum source, CO-0.40-0.22*, with this candidate black hole. Here we present a collation of radio and infrared data at this location. Australia Telescope Compact Array constraints on the radio spectrum, and the detection of a mid-infrared counterpart, are in tension with an Sgr A*-like model for CO-0.40-0.22* despite the comparable bolometric to the Eddington luminosity ratios under the intermediate-mass black hole interpretation. A protostellar-disc scenario is, however, tenable. CO-0.40-0.22(*) is positionally coincident with an arrowhead-shaped infrared-dark cloud (which we call the Freccia Rossa). If the VLSR ≈ 70 km s-1 systemic velocity of CO-0.40-0.22 is common to the entire Freccia Rossa system, we hypothesize that it is the remnant of a high-velocity cloud that has plunged into the Milky Way from the Galactic halo.

Nitration of naphthalene and remarks on the mechanism of electrophilic aromatic nitration.

PubMed

Olah, G A; Narang, S C; Olah, J A

1981-06-01

Naphthalene was nitrated with a variety of nitrating agents. Comparison of data with Perrin's electrochemical nitration [Perrin, C. L. (1977) J. Am. Chem. Soc. 99, 5516-5518] shows that nitration of naphthalene gives an alpha-nitronaphthalene to beta-nitronaphthalene ratio that varies between 9 and 29 and is thus not constant. Perrin's data, therefore, are considered to be inconclusive evidence for the proposed one-electron transfer mechanism for the nitration of naphthalene and other reactive aromatics. Moodie and Schoefield [Hoggett, J. G., Moodie, R. B., Penton, J. R. & Schoefield, K. (1971) Nitration and Aromatic Reactivity (Cambridge Univ. Press, London)], as well as Perrin, independently concluded that, in the general scheme of nitration of reactive aromatics, there is the necessity to introduce into the classical Ingold mechanism an additional step involving a distinct intermediate preceding the formation of the Wheland intermediate (sigma complexes). This view coincides with our two-step mechanistic picture [Kuhn, S. J. & Olah, G. A. (1961) J. Am. Chem. Soc. 83, 4564-4571] of the nitronium salt nitration of aromatic hydrocarbons (including benzene and toluene), in which low substrate selectivity but high positional selectivity was found, indicating the independence of substrate from positional selectivity.

Nitration of naphthalene and remarks on the mechanism of electrophilic aromatic nitration*

PubMed Central

Olah, George A.; Narang, Subhash C.; Olah, Judith A.

1981-01-01

Naphthalene was nitrated with a variety of nitrating agents. Comparison of data with Perrin's electrochemical nitration [Perrin, C. L. (1977) J. Am. Chem. Soc. 99, 5516-5518] shows that nitration of naphthalene gives an α-nitronaphthalene to β-nitronaphthalene ratio that varies between 9 and 29 and is thus not constant. Perrin's data, therefore, are considered to be inconclusive evidence for the proposed one-electron transfer mechanism for the nitration of naphthalene and other reactive aromatics. Moodie and Schoefield [Hoggett, J. G., Moodie, R. B., Penton, J. R. & Schoefield, K. (1971) Nitration and Aromatic Reactivity (Cambridge Univ. Press, London)], as well as Perrin, independently concluded that, in the general scheme of nitration of reactive aromatics, there is the necessity to introduce into the classical Ingold mechanism an additional step involving a distinct intermediate preceding the formation of the Wheland intermediate (σ complexes). This view coincides with our two-step mechanistic picture [Kuhn, S. J. & Olah, G. A. (1961) J. Am. Chem. Soc. 83, 4564-4571] of the nitronium salt nitration of aromatic hydrocarbons (including benzene and toluene), in which low substrate selectivity but high positional selectivity was found, indicating the independence of substrate from positional selectivity. PMID:16593026

Native Frames: Disentangling Sequential from Concerted Three-Body Fragmentation

NASA Astrophysics Data System (ADS)

Rajput, Jyoti; Severt, T.; Berry, Ben; Jochim, Bethany; Feizollah, Peyman; Kaderiya, Balram; Zohrabi, M.; Ablikim, U.; Ziaee, Farzaneh; Raju P., Kanaka; Rolles, D.; Rudenko, A.; Carnes, K. D.; Esry, B. D.; Ben-Itzhak, I.

2018-03-01

A key question concerning the three-body fragmentation of polyatomic molecules is the distinction of sequential and concerted mechanisms, i.e., the stepwise or simultaneous cleavage of bonds. Using laser-driven fragmentation of OCS into O++C++S+ and employing coincidence momentum imaging, we demonstrate a novel method that enables the clear separation of sequential and concerted breakup. The separation is accomplished by analyzing the three-body fragmentation in the native frame associated with each step and taking advantage of the rotation of the intermediate molecular fragment, CO2 + or CS2 + , before its unimolecular dissociation. This native-frame method works for any projectile (electrons, ions, or photons), provides details on each step of the sequential breakup, and enables the retrieval of the relevant spectra for sequential and concerted breakup separately. Specifically, this allows the determination of the branching ratio of all these processes in OCS3 + breakup. Moreover, we find that the first step of sequential breakup is tightly aligned along the laser polarization and identify the likely electronic states of the intermediate dication that undergo unimolecular dissociation in the second step. Finally, the separated concerted breakup spectra show clearly that the central carbon atom is preferentially ejected perpendicular to the laser field.

Conjugates of ubiquitin cross-reactive protein distribute in a cytoskeletal pattern.

PubMed Central

Loeb, K R; Haas, A L

1994-01-01

Ubiquitin cross-reactive protein (UCRP), a 15-kDa interferon-induced protein, is a sequence homolog of ubiquitin that is covalently ligated to intracellular proteins in a parallel enzymatic reaction and is found at low levels within cultured cell lines and human tissues not exposed to interferon. Ubiquitin and UCRP ligation reactions apparently target distinct subsets of intracellular proteins, as judged from differences in the distributions of the respective adducts revealed on immunoblots. In this study, successive passages of the human lung carcinoma line A549 in the presence of neutralizing antibodies against alpha and beta interferons had no effect on the levels of either free or conjugated UCRP, indicating that these UCRP pools are constitutively present within uninduced cells and are thus not a consequence of autoinduction by low levels of secreted alpha/beta interferon. In an effort to identify potential targets for UCRP conjugation, the immunocytochemical distribution of UCRP was examined by using affinity-purified polyclonal antibodies against recombinant polypeptide. UCRP distributes in a punctate cytoskeletal pattern that is resistant to extraction by nonionic detergents (e.g., Triton X-100) in both uninduced and interferon-treated A549 cells. The cytoskeletal pattern colocalizes with the intermediate filament network of epithelial and mesothelial cell lines. Immunoblots of parallel Triton X-100-insoluble cell extracts suggest that the cytoskeletal association largely results from the noncovalent association of UCRP conjugates with the intermediate filaments rather than direct ligation of the polypeptide to structural components of the filaments. A significant increase in the sequestration of UCRP adducts on intermediate filaments accompanies interferon induction. These results suggest that UCRP may serve as a trans-acting binding factor directing the association of ligated target proteins to intermediate filaments. Images PMID:7526157

Impacts of parturition and body condition score on glucose uptake capacity of bovine monocyte subsets.

PubMed

Eger, Melanie; Hussen, Jamal; Drong, Caroline; Meyer, Ulrich; von Soosten, Dirk; Frahm, Jana; Daenicke, Sven; Breves, Gerhard; Schuberth, Hans-Joachim

2015-07-15

The peripartal period of dairy cows is associated with a higher incidence of infectious diseases like mastitis or metritis, particularly in high-yielding animals. The onset of lactation induces a negative energy balance and a shift of glucose distribution toward the udder. Glucose is used as primary fuel by monocytes which give rise to macrophages, key cells in the defense against pathogens. The aim of this study was to analyze whether animals with high or low body condition score (BCS) differ in composition and glucose uptake capacities of bovine monocyte subsets. Blood samples were taken from 27 dairy cows starting 42 days before parturition until day 56 after parturition. The cows were allocated to two groups according to their BCS. A feeding regime was applied, in which the BCS high group received higher amounts of concentrate before parturition and concentrate feeding was more restricted in the BCS high group after parturition compared with the BCS low group, to promote postpartal lipolysis and enhance negative energy balance in the BCS high group. Blood cell counts of classical (cM), intermediate (intM) and nonclassical monocytes (ncM) were increased at day 7 after calving. In the BCS low group intM numbers were significantly higher compared to the BCS high group at day 7 after parturition. Within the BCS low group cows suffering from mastitis or metritis showed significantly higher numbers of cM, intM and ncM at day 7 after parturition. Classical monocytes and intM showed similar glucose uptake capacities while values for ncM were significantly lower. Compared with antepartal capacities and irrespective of BCS and postpartal mastitis or metritis, glucose uptake of all monocyte subsets decreased after parturition. In conclusion, whereas glucose uptake capacity of bovine monocyte subsets is altered by parturition, it is not linked to the energy supply of the animals or to postpartal infectious diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH17 cytokine interleukin-22

PubMed Central

Hughes, Tiffany; Becknell, Brian; McClory, Susan; Briercheck, Edward; Freud, Aharon G.; Zhang, Xiaoli; Mao, Hsiaoyin; Nuovo, Gerard; Yu, Jianhua

2009-01-01

Considerable functional heterogeneity within human natural killer (NK) cells has been revealed through the characterization of distinct NK-cell subsets. Accordingly, a small subset of CD56+NKp44+NK cells, termed NK-22 cells, was recently described within secondary lymphoid tissue (SLT) as IL-22− when resting, with a minor fraction of this population becoming IL-22+ when activated. Here we discover that the vast majority of stage 3 immature NK (iNK) cells in SLT constitutively and selectively express IL-22, a TH17 cytokine important for mucosal immunity, whereas earlier and later stages of NK developmental intermediates do not express IL-22. These iNK cells have a surface phenotype of CD34−CD117+CD161+CD94−, largely lack expression of NKp44 and CD56, and do not produce IFN-γ or possess cytolytic activity. In summary, stage 3 iNK cells are highly enriched for IL-22 and IL-26 messenger RNA, and IL-22 protein production, but do not express IL-17A or IL-17F. PMID:19244159

A distinct dendritic cell population arises in the thymus of IL-13Rα1-sufficient but not IL-13Rα1-deficient mice.

PubMed

Barik, Subhasis; Miller, Mindy; Cattin-Roy, Alexis; Ukah, Tobechukwu; Zaghouani, Habib

2018-06-18

IL-13 receptor alpha 1 (IL-13Rα1) associates with IL-4Rα to form a functional IL-4Rα/IL-13Rα1 heteroreceptor (HR) through which both IL-4 and IL-13 signal. Recently, HR expression was associated with the development of M2 type macrophages which function as antigen presenting cells (APCs). Herein, we show that a subset of thymic resident dendritic cells (DCs) expressing high CD11b (CD11b hi ) and intermediate CD11c (CD11c int ) arise in HR-sufficient but not HR-deficient mice. These DCs, which originate from the bone marrow are able to take up Ag from the peritoneum, traffic through the spleen and the lymph nodes and carry it to the thymus. In addition, since the DCs are able to present Ag to T cells, express high levels of the costimulatory molecule CD24, and comprise a CD8α + subset, it is likely that the cells contribute to T cell development and perhaps negative selection of self-reactive lymphocytes. Copyright © 2018 Elsevier Inc. All rights reserved.

Low-Dose-Rate Brachytherapy Versus Cryotherapy in Low- and Intermediate-Risk Prostate Cancer

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

Gestaut, Matthew M., E-mail: Matthew.Gestaut@BSWHealth.org; Cai, Wendi; Vyas, Shilpa

Purpose: Cryotherapy and brachytherapy are definitive local treatment options for low- to intermediate-risk prostate cancer. There are both prospective and retrospective data for brachytherapy, but the use of cryotherapy has been limited primarily to single-institution retrospective studies. Currently, no published evidence has compared low-dose-rate brachytherapy versus cryotherapy. Methods and Materials: Institutional review board approval was obtained to conduct a retrospective chart review of consecutive patients treated at our institution from 1990 to 2012. For inclusion, patients must have received a prostate cancer diagnosis and have been considered to have low- to intermediate-risk disease according to the National Comprehensive Cancer Networkmore » criteria. All patients received brachytherapy or cryotherapy treatment. Disease specifics and failure details were collected for all patients. Failure was defined as prostate-specific antigen nadir +2 ng/mL. Results: A total of 359 patients were analyzed. The groups comprised 50 low-risk cryotherapy (LRC), 92 intermediate-risk cryotherapy (IRC), 133 low-risk brachytherapy (LRB), and 84 intermediate-risk brachytherapy (IRB) patients. The median prostate-specific antigen follow-up periods were 85.6 months (LRC), 59.2 months (IRC), 74.9 months (LRB), and 59.8 months (IRB). The 5-year biochemical progression–free survival (bPFS) rate was 57.9% in the cryotherapy group versus 89.6% in the brachytherapy group (P<.0001). The 5-year bPFS rate was 70.0% (LRC), 51.4% (IRC), 89.4% (LRB), and 89.7% (IRB). The bPFS rate was significantly different between brachytherapy and cryotherapy for low- and intermediate-risk groups (P<.05). The mean nadir temperature reached for cryotherapy patients was −35°C (range, −96°C to −6°C). Cryotherapy used a median of 2 freeze-thaw cycles (range, 2-4 freeze-thaw cycles). Conclusions: Results from this study suggest that cryotherapy is inferior to brachytherapy for patients with low- to intermediate-risk prostate cancer. Patient selection criteria for consideration of cryotherapy and brachytherapy are similar in terms of anesthesia candidacy. Therefore, cryotherapy would not be recommended as a first-line local therapy for this particular patient subset.« less

High EVI1 expression is associated with MLL rearrangements and predicts decreased survival in paediatric acute myeloid leukaemia: a report from the children's oncology group.

PubMed

Ho, Phoenix A; Alonzo, Todd A; Gerbing, Robert B; Pollard, Jessica A; Hirsch, Betsy; Raimondi, Susana C; Cooper, Todd; Gamis, Alan S; Meshinchi, Soheil

2013-09-01

Ectopic viral integration site-1 (EVI1) is highly expressed in certain cytogenetic subsets of adult acute myeloid leukaemia (AML), and has been associated with inferior survival. We sought to examine the clinical and biological associations of EVI1(high) , defined as expression in excess of normal controls, in paediatric AML. EVI1 mRNA expression was measured via quantitative real-time polymerase chain reaction in diagnostic specimens obtained from 206 patients. Expression levels were correlated with clinical features and outcome. EVI1(high) was present in 58/206 (28%) patients. MLL rearrangements occurred in 40% of EVI1(high) patients as opposed to 12% of the EVI1(low/absent) patients (P < 0·001). No abnormalities of 3q26 were found in EVI1(high) patients by conventional cytogenetic analysis, nor were cryptic 3q26 abnormalities detected in a subset of patients screened by next-generation sequencing. French-American-British class M7 was enriched in the EVI1(high) group, accounting for 24% of these patients. EVI1(high) patients had significantly lower 5-year overall survival from study entry (51% vs. 68%, P = 0·015). However, in multivariate analysis including other established prognostic markers, EVI1 expression did not retain independent prognostic significance. EVI1 expression is currently being studied in a larger cohort of patients enrolled on subsequent Children's Oncology Group trials, to determine if EVI1(high) has prognostic value in MLL-rearranged or intermediate-risk subsets. © 2013 John Wiley & Sons Ltd.

Memory Elicited by Courtship Conditioning Requires Mushroom Body Neuronal Subsets Similar to Those Utilized in Appetitive Memory.

PubMed

Montague, Shelby A; Baker, Bruce S

2016-01-01

An animal's ability to learn and to form memories is essential for its survival. The fruit fly has proven to be a valuable model system for studies of learning and memory. One learned behavior in fruit flies is courtship conditioning. In Drosophila courtship conditioning, male flies learn not to court females during training with an unreceptive female. He retains a memory of this training and for several hours decreases courtship when subsequently paired with any female. Courtship conditioning is a unique learning paradigm; it uses a positive-valence stimulus, a female fly, to teach a male to decrease an innate behavior, courtship of the female. As such, courtship conditioning is not clearly categorized as either appetitive or aversive conditioning. The mushroom body (MB) region in the fruit fly brain is important for several types of memory; however, the precise subsets of intrinsic and extrinsic MB neurons necessary for courtship conditioning are unknown. Here, we disrupted synaptic signaling by driving a shibirets effector in precise subsets of MB neurons, defined by a collection of split-GAL4 drivers. Out of 75 lines tested, 32 showed defects in courtship conditioning memory. Surprisingly, we did not have any hits in the γ lobe Kenyon cells, a region previously implicated in courtship conditioning memory. We did find that several γ lobe extrinsic neurons were necessary for courtship conditioning memory. Overall, our memory hits in the dopaminergic neurons (DANs) and the mushroom body output neurons were more consistent with results from appetitive memory assays than aversive memory assays. For example, protocerebral anterior medial DANs were necessary for courtship memory, similar to appetitive memory, while protocerebral posterior lateral 1 (PPL1) DANs, important for aversive memory, were not needed. Overall, our results indicate that the MB circuits necessary for courtship conditioning memory coincide with circuits necessary for appetitive memory.

Memory Elicited by Courtship Conditioning Requires Mushroom Body Neuronal Subsets Similar to Those Utilized in Appetitive Memory

PubMed Central

Montague, Shelby A.; Baker, Bruce S.

2016-01-01

An animal’s ability to learn and to form memories is essential for its survival. The fruit fly has proven to be a valuable model system for studies of learning and memory. One learned behavior in fruit flies is courtship conditioning. In Drosophila courtship conditioning, male flies learn not to court females during training with an unreceptive female. He retains a memory of this training and for several hours decreases courtship when subsequently paired with any female. Courtship conditioning is a unique learning paradigm; it uses a positive-valence stimulus, a female fly, to teach a male to decrease an innate behavior, courtship of the female. As such, courtship conditioning is not clearly categorized as either appetitive or aversive conditioning. The mushroom body (MB) region in the fruit fly brain is important for several types of memory; however, the precise subsets of intrinsic and extrinsic MB neurons necessary for courtship conditioning are unknown. Here, we disrupted synaptic signaling by driving a shibirets effector in precise subsets of MB neurons, defined by a collection of split-GAL4 drivers. Out of 75 lines tested, 32 showed defects in courtship conditioning memory. Surprisingly, we did not have any hits in the γ lobe Kenyon cells, a region previously implicated in courtship conditioning memory. We did find that several γ lobe extrinsic neurons were necessary for courtship conditioning memory. Overall, our memory hits in the dopaminergic neurons (DANs) and the mushroom body output neurons were more consistent with results from appetitive memory assays than aversive memory assays. For example, protocerebral anterior medial DANs were necessary for courtship memory, similar to appetitive memory, while protocerebral posterior lateral 1 (PPL1) DANs, important for aversive memory, were not needed. Overall, our results indicate that the MB circuits necessary for courtship conditioning memory coincide with circuits necessary for appetitive memory. PMID:27764141

Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases.

PubMed

Romano, Ryan C; Carter, Jodi M; Folpe, Andrew L

2015-08-01

Malignant melanomas are known to express vimentin, among other intermediate filaments. Though anomalous keratin expression by malignant melanoma has been reported, its frequency is not well-established and this phenomenon is not well-known. We have seen in consultation a number of malignant melanomas with anomalous expression of keratin, other intermediate filaments, or synaptophysin, and therefore studied a large group of primary and metastatic melanomas to determine the frequency of these events. About 73 cases of malignant melanoma (22 primaries and 51 metastases) from 71 patients (51 male, 20 female; mean 59 years, range 17-87 years) were retrieved from our archives. Prior diagnoses were confirmed by re-review of hematoxylin and eosin sections and relevant (e.g., S100 protein, HMB45, Melan-A, and tyrosinase) immunohistochemical studies. Available sections were immunostained for keratin (OSCAR and AE1/AE3 antibodies), desmin, neurofilament protein, glial fibrillary acidic protein, synaptophysin, and chromogranin A. Not all cases could be tested for all markers. Cases were predominantly epithelioid (48/73, 66%) or spindle cell/desmoplastic (25/73, 34%). S100 protein, Melan-A, HMB45, and tyrosinase were positive in 60/65 (92%), 34/64 (53%), 30/60 (50%), 25/48 (52%) of cases, respectively. All five S100-protein-negative cases expressed at least one of the other melanocytic markers: Melan-A (two of four, 50%), HMB45 (two of three, 67%), and tyrosinase (one of two, 50%). All cases expressed at least one melanocytic marker. Cases were positive for keratin (OSCAR, 17/61, 28%; AE1/AE3, 16/40, 40%), desmin (11/47, 24%), neurofilament protein (5/31, 16%), glial fibrillary acidic protein (3/32, 9%), and synaptophysin (10/34, 29%), typically only in a minority of cells. Chromogranin was negative (0/32, 0%). Altogether 9/73 cases (12%) showed expression of >1 intermediate filament. All S100-protein-negative melanomas showed anomalous intermediate filament expression (keratin--one case, desmin--three cases, neurofilament protein--one case). Anomalous intermediate filament or synaptophysin expression was more common in epithelioid (intermediate filament, 27/48, 56%; synaptophysin, 7/22, 32%) as compared with spindle cell/desmoplastic (intermediate filament, 8/25, 32%; synaptophysin, 3/12, 25%) melanomas. Overall, 48% (35/73) of cases showed anomalous expression of at least one intermediate filament. Anomalous expression of all intermediate filaments and synaptophysin was found in significant subsets of malignant melanoma, representing potentially serious diagnostic pitfalls. While the inclusion of consultation cases may inflate the frequency of these findings in this series, similar findings were also seen in institutional cases. Malignant melanoma showing anomalous intermediate filament and synaptophysin expression may easily be mistaken for carcinomas, rhabdomyosarcomas, and neuroendocrine tumors. Awareness of this phenomenon, careful histopathological evaluation, and an appropriate melanocytic immunohistochemical panel should facilitate the diagnosis of malignant melanoma with unusual immunophenotypes.

Predicting features of breast cancer with gene expression patterns.

PubMed

Lu, Xuesong; Lu, Xin; Wang, Zhigang C; Iglehart, J Dirk; Zhang, Xuegong; Richardson, Andrea L

2008-03-01

Data from gene expression arrays hold an enormous amount of biological information. We sought to determine if global gene expression in primary breast cancers contained information about biologic, histologic, and anatomic features of the disease in individual patients. Microarray data from the tumors of 129 patients were analyzed for the ability to predict biomarkers [estrogen receptor (ER) and HER2], histologic features [grade and lymphatic-vascular invasion (LVI)], and stage parameters (tumor size and lymph node metastasis). Multiple statistical predictors were used and the prediction accuracy was determined by cross-validation error rate; multidimensional scaling (MDS) allowed visualization of the predicted states under study. Models built from gene expression data accurately predict ER and HER2 status, and divide tumor grade into high-grade and low-grade clusters; intermediate-grade tumors are not a unique group. In contrast, gene expression data is inaccurate at predicting tumor size, lymph node status or LVI. The best model for prediction of nodal status included tumor size, LVI status and pathologically defined tumor subtype (based on combinations of ER, HER2, and grade); the addition of microarray-based prediction to this model failed to improve the prediction accuracy. Global gene expression supports a binary division of ER, HER2, and grade, clearly separating tumors into two categories; intermediate values for these bio-indicators do not define intermediate tumor subsets. Results are consistent with a model of regional metastasis that depends on inherent biologic differences in metastatic propensity between breast cancer subtypes, upon which time and chance then operate.

A cross-jurisdictional evaluation of insurance coverage among HIV care patients following the Affordable Care Act.

PubMed

Hood, Julia E; Buskin, Susan E; Anderson, Bridget J; Gagner, Alexandra; Kienzle, Jennifer; Maggio, David; Markey, Katie; Reuer, Jennifer; Benbow, Nanette; Wortley, Pascale

2017-04-01

The impact of the Affordable Care Act (ACA) on HIV care patients, aged 18-64, was evaluated in three jurisdictions with Medicaid expansion (Chicago, New York State, and Washington) and three jurisdictions without Medicaid expansion (Georgia, Texas, and Virginia) using data from the Medical Monitoring Project. Multivariate regression models were used to evaluate insurance status that was reported pre- and post-ACA; self-reported impact of ACA on HIV care was explored with descriptive statistics. The likelihood of having insurance was significantly greater post-ACA compared to pre-ACA in Chicago (aRR = 1.33, 95%CI = 1.20, 1.47), Washington (aRR = 1.15, 95%CI = 1.08, 1.22), and Virginia (aRR = 1.14, 95%CI = 1.00, 1.29). In Washington and Chicago, the likelihood of being Medicaid-insured was greater post-ACA compared to pre-ACA implementation (Chicago: aRR = 1.25, 95%CI = 1.03,1.53; Washington: aRR = 1.66 95% CI = 1.30, 2.13). No other significant differences were observed. Only a subset of HIV care patients (range: 15-35%) reported a change in insurance that would have coincided with the implementation of ACA; and within this subset, a change in medical care costs was the most commonly noted issue. In conclusion, the influence of ACA on insurance coverage and other factors affecting HIV care likely varies by jurisdiction.

Characterization of Gastric and Neuronal Histaminergic Populations Using a Transgenic Mouse Model

PubMed Central

Walker, Angela K.; Park, Won-Mee; Chuang, Jen-Chieh; Perello, Mario; Sakata, Ichiro; Osborne-Lawrence, Sherri; Zigman, Jeffrey M.

2013-01-01

Histamine is a potent biogenic amine that mediates numerous physiological processes throughout the body, including digestion, sleep, and immunity. It is synthesized by gastric enterochromaffin-like cells, a specific set of hypothalamic neurons, as well as a subset of white blood cells, including mast cells. Much remains to be learned about these varied histamine-producing cell populations. Here, we report the validation of a transgenic mouse line in which Cre recombinase expression has been targeted to cells expressing histidine decarboxylase (HDC), which catalyzes the rate-limiting step in the synthesis of histamine. This was achieved by crossing the HDC-Cre mouse line with Rosa26-tdTomato reporter mice, thus resulting in the expression of the fluorescent Tomato (Tmt) signal in cells containing Cre recombinase activity. As expected, the Tmt signal co-localized with HDC-immunoreactivity within the gastric mucosa and gastric submucosa and also within the tuberomamillary nucleus of the brain. HDC expression within Tmt-positive gastric cells was further confirmed by quantitative PCR analysis of mRNA isolated from highly purified populations of Tmt-positive cells obtained by fluorescent activated cell sorting (FACS). HDC expression within these FACS-separated cells was found to coincide with other markers of both ECL cells and mast cells. Gastrin expression was co-localized with HDC expression in a subset of histaminergic gastric mucosal cells. We suggest that these transgenic mice will facilitate future studies aimed at investigating the function of histamine-producing cells. PMID:23555941

Role of cytoskeleton in regulating fusion of nucleoli: a study using the activated mouse oocyte model.

PubMed

Lian, Hua-Yu; Jiao, Guang-Zhong; Wang, Hui-Li; Tan, Xiu-Wen; Wang, Tian-Yang; Zheng, Liang-Liang; Kong, Qiao-Qiao; Tan, Jing-He

2014-09-01

Although fusion of nucleoli was observed during pronuclear development of zygotes and the behavior of nucleoli in pronuclei has been suggested as an indicator of embryonic developmental potential, the mechanism for nucleolar fusion is unclear. Although both cytoskeleton and the nucleolus are important cellular entities, there are no special reports on the relationship between the two. Role of cytoskeleton in regulating fusion of nucleoli was studied using the activated mouse oocyte model. Mouse oocytes were cultured for 6 h in activating medium (Ca²⁺-free CZB medium containing 10 mM SrCl₂) supplemented with or without inhibitors for cytoskeleton or protein synthesis before pronuclear formation, nucleolar fusion, and the activity of maturation-promoting factor (MPF) were examined. Whereas treatment with microfilament inhibitor cytochalasin D or B or intermediate filament inhibitor acrylamide suppressed nucleolar fusion efficiently, treatment with microtubule inhibitor demecolcine or nocodazole or protein synthesis inhibitor cycloheximide had no effect. The cytochalasin D- or acrylamide-sensitive temporal window coincided well with the reported temporal window for nucleolar fusion in activated oocytes. Whereas a continuous incubation with demecolcine prevented pronuclear formation, pronuclei formed normally when demecolcine was excluded during the first hour of activation treatment when the MPF activity dropped dramatically. The results suggest that 1) microfilaments and intermediate filaments but not microtubules support nucleolar fusion, 2) proteins required for nucleolar fusion including microfilaments and intermediate filaments are not de novo synthesized, and 3) microtubule disruption prevents pronuclear formation by activating MPF. © 2014 by the Society for the Study of Reproduction, Inc.

Changes in northeast Atlantic hydrology during Termination 1: Insights from Celtic margin's benthic foraminifera

NASA Astrophysics Data System (ADS)

Mojtahid, M.; Toucanne, S.; Fentimen, R.; Barras, C.; Le Houedec, S.; Soulet, G.; Bourillet, J.-F.; Michel, E.

2017-11-01

Using benthic foraminiferal-based proxies in sediments from the Celtic margin, we provide a well-dated record across the last deglaciation of the Channel River dynamics and its potential impact on the hydrology of intermediate water masses along the European margin. Our results describe three main periods: 1) During the Last Glacial Maximum, and before ∼21 ka BP, the predominance of meso-oligotrophic species suggests well oxygenated water masses. After ∼21 ka BP, increasing proportions of eutrophic species related to enhanced riverine supply occurs concomitantly with early warming in Greenland air-temperatures; 2) A thick laminated deposit, occurring during a 1500-years long period of seasonal melting of the European Ice Sheet (EIS), is associated with early Heinrich Stadial 1 period (∼18.2-16.7 ka BP). The benthic proxies describe low salinity episodes, cold temperatures, severe dysoxia and eutrophic conditions on the sea floor, perhaps evidence for cascading of turbid meltwaters; 3) During late HS1 (∼16.7-14.7 ka BP), conditions on the Celtic margin's seafloor changed drastically and faunas indicate oligotrophic conditions as a result of the ceasing of EIS meltwater discharges. While surface waters were cold due to Laurentide Ice Sheet (LIS) icebergs releases, increasing benthic Mg/Ca ratios reveal a progressive warming of intermediate water masses whereas oxygen proxies indicate overall well oxygenated conditions. In addition to the well known effect of EIS meltwaters on surface waters in the Celtic margin, our benthic record documents a pronounced impact on intermediate water depths during HS1, which coincided with major AMOC disruptions.

Three-body dissociation of OCS3+: Separating sequential and concerted pathways

NASA Astrophysics Data System (ADS)

Kumar, Herendra; Bhatt, Pragya; Safvan, C. P.; Rajput, Jyoti

2018-02-01

Events from the sequential and concerted modes of the fragmentation of OCS3+ that result in coincident detection of fragments C+, O+, and S+ have been separated using a newly proposed representation. An ion beam of 1.8 MeV Xe9+ is used to make the triply charged molecular ion, with the fragments being detected by a recoil ion momentum spectrometer. By separating events belonging exclusively to the sequential mode of breakup, the electronic states of the intermediate molecular ion (CO2+ or CS2+) involved are determined, and from the kinetic energy release spectra, it is shown that the low lying excited states of the parent OCS3+ are responsible for this mechanism. An estimate of branching ratios of events coming from sequential versus concerted mode is presented.

Investigating the limits of PET/CT imaging at very low true count rates and high random fractions in ion-beam therapy monitoring.

PubMed

Kurz, Christopher; Bauer, Julia; Conti, Maurizio; Guérin, Laura; Eriksson, Lars; Parodi, Katia

2015-07-01

External beam radiotherapy with protons and heavier ions enables a tighter conformation of the applied dose to arbitrarily shaped tumor volumes with respect to photons, but is more sensitive to uncertainties in the radiotherapeutic treatment chain. Consequently, an independent verification of the applied treatment is highly desirable. For this purpose, the irradiation-induced β(+)-emitter distribution within the patient is detected shortly after irradiation by a commercial full-ring positron emission tomography/x-ray computed tomography (PET/CT) scanner installed next to the treatment rooms at the Heidelberg Ion-Beam Therapy Center (HIT). A major challenge to this approach is posed by the small number of detected coincidences. This contribution aims at characterizing the performance of the used PET/CT device and identifying the best-performing reconstruction algorithm under the particular statistical conditions of PET-based treatment monitoring. Moreover, this study addresses the impact of radiation background from the intrinsically radioactive lutetium-oxyorthosilicate (LSO)-based detectors at low counts. The authors have acquired 30 subsequent PET scans of a cylindrical phantom emulating a patientlike activity pattern and spanning the entire patient counting regime in terms of true coincidences and random fractions (RFs). Accuracy and precision of activity quantification, image noise, and geometrical fidelity of the scanner have been investigated for various reconstruction algorithms and settings in order to identify a practical, well-suited reconstruction scheme for PET-based treatment verification. Truncated listmode data have been utilized for separating the effects of small true count numbers and high RFs on the reconstructed images. A corresponding simulation study enabled extending the results to an even wider range of counting statistics and to additionally investigate the impact of scatter coincidences. Eventually, the recommended reconstruction scheme has been applied to exemplary postirradiation patient data-sets. Among the investigated reconstruction options, the overall best results in terms of image noise, activity quantification, and accurate geometrical recovery were achieved using the ordered subset expectation maximization reconstruction algorithm with time-of-flight (TOF) and point-spread function (PSF) information. For this algorithm, reasonably accurate (better than 5%) and precise (uncertainty of the mean activity below 10%) imaging can be provided down to 80,000 true coincidences at 96% RF. Image noise and geometrical fidelity are generally improved for fewer iterations. The main limitation for PET-based treatment monitoring has been identified in the small number of true coincidences, rather than the high intrinsic random background. Application of the optimized reconstruction scheme to patient data-sets results in a 25% - 50% reduced image noise at a comparable activity quantification accuracy and an improved geometrical performance with respect to the formerly used reconstruction scheme at HIT, adopted from nuclear medicine applications. Under the poor statistical conditions in PET-based treatment monitoring, improved results can be achieved by considering PSF and TOF information during image reconstruction and by applying less iterations than in conventional nuclear medicine imaging. Geometrical fidelity and image noise are mainly limited by the low number of true coincidences, not the high LSO-related random background. The retrieved results might also impact other emerging PET applications at low counting statistics.

Induction and Maintenance of CX3CR1-Intermediate Peripheral Memory CD8+ T Cells by Persistent Viruses and Vaccines.

PubMed

Gordon, Claire Louse; Lee, Lian Ni; Swadling, Leo; Hutchings, Claire; Zinser, Madeleine; Highton, Andrew John; Capone, Stefania; Folgori, Antonella; Barnes, Eleanor; Klenerman, Paul

2018-04-17

The induction and maintenance of T cell memory is critical to the success of vaccines. A recently described subset of memory CD8 + T cells defined by intermediate expression of the chemokine receptor CX3CR1 was shown to have self-renewal, proliferative, and tissue-surveillance properties relevant to vaccine-induced memory. We tracked these cells when memory is sustained at high levels: memory inflation induced by cytomegalovirus (CMV) and adenovirus-vectored vaccines. In mice, both CMV and vaccine-induced inflationary T cells showed sustained high levels of CX3R1 int cells exhibiting an effector-memory phenotype, characteristic of inflationary pools, in early memory. In humans, CX3CR1 int CD8 + T cells were strongly induced following adenovirus-vectored vaccination for hepatitis C virus (HCV) (ChAd3-NSmut) and during natural CMV infection and were associated with a memory phenotype similar to that in mice. These data indicate that CX3CR1 int cells form an important component of the memory pool in response to persistent viruses and vaccines in both mice and humans. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Copepod (Crustacea) emergence from soils from everglades marshes with different hydroperiods

USGS Publications Warehouse

Loftus, W.F.; Reid, J.W.

2000-01-01

During a severe drought period in the winter and spring of 1989, we made three collections of dried marsh soils from freshwater sloughs in Everglades National Park, Florida, at sites characterized by either long or intermediate annual periods of flooding (hydroperiod). After rehydrating the soils in aquaria, we documented the temporal patterns of copepod emergence over two-week periods. The species richness of copepods in the rehydrated soils was lower than in pre-drought samples from the same slough sites. Only six of the 16 species recorded from the Everglades emerged in the aquarium tests. The long hydroperiod site had a slightly different assemblage and higher numbers of most species than the intermediate-hydroperiod sites. More individuals and species emerged from the early dry-season samples compared with samples taken later in the dry season. The harpacticoid, Cletocamptus deitersi, and the cyclopoid, Microcyclops rubellus, were abundant at most sites. The cyclopoids - Ectocyclops phaleratus, Homocyclops ater, and Paracyclops chiltoni - are new records for the Everglades. We infer that 1) only a subset of Everglades copepod species can survive drought by resting in soils; and that 2) survival ability over time differs by species.

Simvastatin inhibits Staphylococcus aureus host cell invasion through modulation of isoprenoid intermediates

PubMed Central

Horn, Mary P.; Knecht, Sharmon M.; Rushing, Frances L.; Birdsong, Julie; Siddall, C. Parker; Johnson, Charron M.; Abraham, Terri N.; Brown, Amy; Volk, Catherine B.; Gammon, Kelly; Bishop, Derron L.; McKillip, John L.; McDowell, Susan A.

2015-01-01

Patients on a statin regimen are at a decreased risk of death due to bacterial sepsis. We have found that protection by simvastatin includes the inhibition of host cell invasion by Staphylococcus aureus, the most common etiologic agent of sepsis. Inhibition was due in part to depletion of isoprenoid intermediates within the cholesterol biosynthesis pathway and led to the cytosolic accumulation of the small-guanosine triphosphatases (GTPases) CDC42, Rac, and RhoB. Actin stress fiber disassembly required for host invasion was attenuated by simvastatin and by the inhibition of phosphoinositide 3-kinase (PI3K) activity. PI3K relies on coupling to prenylated proteins, such as this subset of small-GTPases, for access to membrane-bound phosphoinositide to mediate stress fiber disassembly. Therefore, we examined whether simvastatin restricts PI3K cellular localization. In response to simvastatin, the PI3K isoform p85, coupled to these small-GTPases, was sequestered within the cytosol. From these findings, we propose a mechanism whereby simvastatin restricts p85 localization, inhibiting actin dynamics required for bacterial endocytosis. This may provide the basis for protection at the level of the host in invasive infections by S. aureus. PMID:18388257

Manifestations of Dynamic Strain Aging in Soft-Oriented NiAl Single Crystals

NASA Technical Reports Server (NTRS)

Weaver, M. L.; Kaufman, M. J.; Noebe, R. D.

1996-01-01

The tensile and compressive properties of six NiAl-base single-crystal alloys have been investigated at temperatures between 77 and 1200 K. The normalized critical resolved shear stresses (CRSS/E) and work-hardening rates (Theta/E) for these alloys generally decreased with increasing temperature. However, anomalous peaks or plateaus for these properties were observed in conventional purity (CPNiAl), Si-doped (NiAl-Si), C-doped low Si (UF-NiAl1), and Mo-doped (NiAl-Mo) alloys at intermediate temperatures (600 to 1000 K). This anomalous behavior was not observed in high-purity, low interstitial material (HP-NiAl). Low or negative strain-rate sensitivities (SRS) also were observed in all six alloys in this intermediate temperature range. Coincident with the occurrence of negative strain-rate sensitivities was the observation of serrated stress-strain curves in the CPNiAl and NiAl-Si alloys. These phenomena have been attributed to dynamic strain aging (DSA). Chemical analysis of the alloys used in this study suggests that the main specie responsible for strain aging in NiAl is C but indicate that residual Si impurities can enhance the strain aging effects. The corresponding dislocation microstructures at low temperatures (300 to 600 K) were composed of well-defined cells. At intermediate temperatures (600 to 900 K), either poorly defined cells or coarse bands of localized slip, reminiscent of the vein structures observed in low-cycle fatigue specimens deformed in the DSA regime, were observed in conventional purity, Si-doped, and in Mo-doped alloys. In contrast, a well-defined cell structure persisted in the low interstitial, high-purity alloy. At elevated temperatures (greater than or equal to 1000 K), more uniformly distributed dislocations and sub-boundaries were observed in all alloys. These observations are consistent with the occurrence of DSA in NiAl single-crystal alloys at intermediate temperatures.

Surface reaction modification: The effect of structured overlayers of sulfur on the kinetics and mechanism of the decomposition of formic acid on Pt(111)

NASA Astrophysics Data System (ADS)

Abbas, N.; Madix, R. J.

The reaction of formic acid (DCOOH) on Pt(111), Pt(111)-(2×2)S and Pt(111)-(√3×√3)R30°S surfaces was examined by temperature programmed reaction spectroscopy. On the clean surface formic acid decomposed to yield primarily carbon dioxide and the hydrogenic species (H 2, HD and D 2) at low coverages. Although the formation of water and carbon monoxide via a dehydration reaction was observed at these coverages, the yield of these products was small when compared to the other products of reaction. The evolution of CO 2 at low temperature was ascribed to the decomposition of the formate intermediate. In the presence of sulfur the amount of molecularly adsorbed formic acid decreased up to a factor of three on the (√3×√3)R30°S surface, and a decline in the reactivity of over an order of magnitude was also observed. The only products formed were the hydrogenic species and carbon dioxide. The absence of carbon monoxide indicated that the dehydration pathway was blocked by sulfur. In addition to the low temperature CO 2 peak a high temperature CO 2-producing path was also evident. It was inferred from both the stoichiometry and the coincident evolution of D 2 and CO 2 in the high temperature states that these products also evolved due to the decomposition of the formate intermediate. On increasing the sulfur coverage to one-third monolayer this intermediate was further stabilized, and a predominance of the decomposition via the high temperature path was observed. Stability of the formate intermediate was attributed to inhibition of the decomposition reaction by sulfur atoms. The activation energy for formate decomposition increased from 15 kcal/gmole on the clean surface to 24.3 kcal/gmol on the (√3×√3)R30°S overlayer.

Evolution of a strategy for preparing bioactive small molecules by sequential multicomponent assembly processes, cyclizations, and diversification.

PubMed

Sahn, James J; Granger, Brett A; Martin, Stephen F

2014-10-21

A strategy for generating diverse collections of small molecules has been developed that features a multicomponent assembly process (MCAP) to efficiently construct a variety of intermediates possessing an aryl aminomethyl subunit. These key compounds are then transformed via selective ring-forming reactions into heterocyclic scaffolds, each of which possesses suitable functional handles for further derivatizations and palladium-catalyzed cross coupling reactions. The modular nature of this approach enables the facile construction of libraries of polycyclic compounds bearing a broad range of substituents and substitution patterns for biological evaluation. Screening of several compound libraries thus produced has revealed a large subset of compounds that exhibit a broad spectrum of medicinally-relevant activities.

From Verified Models to Verifiable Code

NASA Technical Reports Server (NTRS)

Lensink, Leonard; Munoz, Cesar A.; Goodloe, Alwyn E.

2009-01-01

Declarative specifications of digital systems often contain parts that can be automatically translated into executable code. Automated code generation may reduce or eliminate the kinds of errors typically introduced through manual code writing. For this approach to be effective, the generated code should be reasonably efficient and, more importantly, verifiable. This paper presents a prototype code generator for the Prototype Verification System (PVS) that translates a subset of PVS functional specifications into an intermediate language and subsequently to multiple target programming languages. Several case studies are presented to illustrate the tool's functionality. The generated code can be analyzed by software verification tools such as verification condition generators, static analyzers, and software model-checkers to increase the confidence that the generated code is correct.

Investigating the genetic variation underlying episodicity in major depressive disorder: suggestive evidence for a bipolar contribution.

PubMed

Ferentinos, Panagiotis; Rivera, Margarita; Ising, Marcus; Spain, Sarah L; Cohen-Woods, Sarah; Butler, Amy W; Craddock, Nicholas; Owen, Michael J; Korszun, Ania; Jones, Lisa; Jones, Ian; Gill, Michael; Rice, John P; Maier, Wolfgang; Mors, Ole; Rietschel, Marcella; Lucae, Susanne; Binder, Elisabeth B; Preisig, Martin; Tozzi, Federica; Muglia, Pierandrea; Breen, Gerome; Craig, Ian W; Farmer, Anne E; Müller-Myhsok, Bertram; McGuffin, Peter; Lewis, Cathryn M

2014-02-01

Highly recurrent major depressive disorder (MDD) has reportedly increased risk of shifting to bipolar disorder; high recurrence frequency has, therefore, featured as evidence of 'soft bipolarity'. We aimed to investigate the genetic underpinnings of total depressive episode count in recurrent MDD. Our primary sample included 1966 MDD cases with negative family history of bipolar disorder from the RADIANT studies. Total episode count was adjusted for gender, age, MDD duration, study and center before being tested for association with genotype in two separate genome-wide analyses (GWAS), in the full set and in a subset of 1364 cases with positive family history of MDD (FH+). We also calculated polygenic scores from the Psychiatric Genomics Consortium MDD and bipolar disorder studies. Episodicity (especially intermediate episode counts) was an independent index of MDD familial aggregation, replicating previous reports. The GWAS produced no genome-wide significant findings. The strongest signals were detected in the full set at MAGI1 (p=5.1×10(-7)), previously associated with bipolar disorder, and in the FH+ subset at STIM1 (p=3.9×10(-6) after imputation), a calcium channel signaling gene. However, these findings failed to replicate in an independent Munich cohort. In the full set polygenic profile analyses, MDD polygenes predicted episodicity better than bipolar polygenes; however, in the FH+ subset, both polygenic scores performed similarly. Episode count was self-reported and, therefore, subject to recall bias. Our findings lend preliminary support to the hypothesis that highly recurrent MDD with FH+ is part of a 'soft bipolar spectrum' but await replication in larger cohorts. © 2013 Published by Elsevier B.V.

A Simple Application of Compressed Sensing to Further Accelerate Partially Parallel Imaging

PubMed Central

Miao, Jun; Guo, Weihong; Narayan, Sreenath; Wilson, David L.

2012-01-01

Compressed Sensing (CS) and partially parallel imaging (PPI) enable fast MR imaging by reducing the amount of k-space data required for reconstruction. Past attempts to combine these two have been limited by the incoherent sampling requirement of CS, since PPI routines typically sample on a regular (coherent) grid. Here, we developed a new method, “CS+GRAPPA,” to overcome this limitation. We decomposed sets of equidistant samples into multiple random subsets. Then, we reconstructed each subset using CS, and averaging the results to get a final CS k-space reconstruction. We used both a standard CS, and an edge and joint-sparsity guided CS reconstruction. We tested these intermediate results on both synthetic and real MR phantom data, and performed a human observer experiment to determine the effectiveness of decomposition, and to optimize the number of subsets. We then used these CS reconstructions to calibrate the GRAPPA complex coil weights. In vivo parallel MR brain and heart data sets were used. An objective image quality evaluation metric, Case-PDM, was used to quantify image quality. Coherent aliasing and noise artifacts were significantly reduced using two decompositions. More decompositions further reduced coherent aliasing and noise artifacts but introduced blurring. However, the blurring was effectively minimized using our new edge and joint-sparsity guided CS using two decompositions. Numerical results on parallel data demonstrated that the combined method greatly improved image quality as compared to standard GRAPPA, on average halving Case-PDM scores across a range of sampling rates. The proposed technique allowed the same Case-PDM scores as standard GRAPPA, using about half the number of samples. We conclude that the new method augments GRAPPA by combining it with CS, allowing CS to work even when the k-space sampling pattern is equidistant. PMID:22902065

Paleoenvironmental events during the last 13,000 years in the central Red Sea as recorded by pteropoda

NASA Astrophysics Data System (ADS)

Almogi-Labin, Ahuva; Hemleben, Christoph; Meischner, Dieter; Erlenkeuser, Helmut

1991-02-01

A high-resolution record was obtained by investigating a sedimentary sequence from two cores taken in the central Red Sea (R/V Meteor cruise 5, leg 2). The numerical variations between nonmigratory and migratory pteropods and their stable isotopic record were studied together with variations in the carbonate and total organic carbon content in order to estimate changes in the structure of the water column during the last 13 kyr. The results indicate the existence of a highly stratified water column during deglaciation and early Holocene (13-8.5 ka). During this period the depth of the mixed layer varied between less than 50-100 m at most, and productivity was markedly reduced in comparison to the recent situation. The intermediate and deep water were constantly highly depleted in oxygen. A pronounced Younger Dryas event was recognized at 10.4 ka which coincides with an arid phase on the border land. The oxygenation of the intermediate water improved remarkably after 7.5 ka and peaked during the period between 4.6 and 2.0 ka. During this period the mixed layer reached its present depth and the productivity which was maximal during middle Holocene attained present level during the last 4.6 kyr.

IRAS 21391 + 5802 - A study in intermediate mass star formation

NASA Technical Reports Server (NTRS)

Wilking, Bruce; Mundy, Lee; Mcmullin, Joseph; Hezel, Thomas; Keene, Jocelyn

1993-01-01

We present infrared and millimeter wavelength observations of the cold IRAS source 21391 + 5802 and its associated molecular core. Infrared observations at lambda = 3.5 microns reveal a heavily obscured, central point source which is coincident with a compact lambda = 2.7 mm continuum and C18O emission region. The source radiates about 310 solar luminosities, primarily at FIR wavelengths, suggesting that it is a young stellar object of intermediate mass. The steeply rising spectral energy distribution and the large fraction of the system mass residing in circumstellar material imply that IRAS 21391 + 5802 is in an early stage of evolution. The inferred dust temperature indicates a temperature gradient in the core. A comprehensive model for the surrounding core of dust and gas is devised to match the observed dust continuum emission and multitransition CS emission from this and previous studies. We find a r exp -1.5 +/- 0.2 density gradient consistent with that of a gravitationally evolved core and a total core mass of 380 solar masses. The observed dust emission is most consistent with a lambda exp -1.5 - lambda exp -2 dust emissivity law; for a lambda exp -2 law, the data are best fit by a mass opacity coefficient of 3.6 x 10 exp -3 sq cm/g at lambda = 1.25 mm.

Trepanation in South-Central Peru during the early late intermediate period (ca. AD 1000-1250).

PubMed

Kurin, Danielle S

2013-12-01

This study evaluates trepanations from five well-contextualized prehistoric sites in the south-central highlands of Andahuaylas, Peru. The emergence of trepanation in this region coincides with the collapse of the Wari Empire, ca. ad 1000. Thirty-two individuals from Andahuaylas, AMS radiocarbon dated to the early Late Intermediate Period (ca. ad 1000-1250), were found to have 45 total trepanations. Various surgical techniques were being employed concurrently throughout the region. Scraping trepanations evinced the highest survival rate; circular grooving, drilling and boring, and linear cutting were far less successful. Evidence of perioperative procedures like hair shaving, poultice application, and possible cranioplasty use aimed to ensure the survival of a trepanation recipient. Postmortem trepanations, also present in Andahuaylas, were likely executed on corpses as a means of better understanding cranial anatomy and improving techniques. Similarities in trepanation patterns throughout the region attest to common motivations to engage in surgery. Although moderate physical head trauma seems to be the impetus for intervention in many cases of trepanation, other motivations included physiological and possibly psychosomatic factors. Nevertheless, treatment was not for everyone. In Andahuaylas, trepanations were withheld from subadults, females, and those individuals who practiced cranial modification. Copyright © 2013 Wiley Periodicals, Inc.

A Tidal Disruption Event in a Nearby Galaxy Hosting an Intermediate Mass Black Hole

NASA Technical Reports Server (NTRS)

Donato, D; Cenko, S. B.; Covino, S.; Troja, E.; Pursimo, T.; Cheung, C. C.; Fox, O.; Kutyrev, A.; Campana, S.; Fugazza, D.;

Effects of latitudinal changes in the oxygen minimum zone of the northeast Pacific on the distribution of bathyal benthic decapod crustaceans

NASA Astrophysics Data System (ADS)

Papiol, Vanesa; Hendrickx, Michel E.; Serrano, David

2017-03-01

The presence of an Oxygen Minimum Zone (OMZ) is one of the major characteristics of the eastern Pacific. The OMZ changes strongly adjacent to Mexico in its thickness and intensity. The ecological impacts of those changes were studied by examining the community structures of bathyal benthic and bentho-pelagic decapod crustaceans, and their oceanographic contexts, on the Mexican Pacific slope along a wide latitudinal range (16-32°N). Decapod crustaceans were collected with a benthic sledge from 48 stations between 865 and 2165 m in three main areas: offshore of northern Baja California (NBC), off southern Baja California (SBC) and in the southern Mexican Pacific (SMP). Physical-chemical parameters were measured in the water column, and sediment composition was analyzed for each station. The narrowing and weakening of the OMZ north of ca. 26°N was confirmed. Water with dissolved oxygen <0.5 ml l-1 occupied a stratum of 1231 m in the SMP vs. only 664 m off NBC. The strongest changes coincided with a region of surface, subsurface and intermediate water mass transitions, where less saline waters from the north extended to depths of ca. 1000 m. Sand proportions were higher in sediments to the south, whereas silt dominated offshore of NBC. A strong latitudinal shift in decapod community composition and bathymetric distribution occurred from off SBC to off NBC, coinciding with changes in oceanographic conditions. The dominant genera of decapod crustaceans at slope depths were cognate to those dominating slope areas in other tropical and subtropical regions of the world. In the SMP and off SBC, large aggregations of organisms were observed at 900-1300 m, with a sharp decrease in abundance at greater depth. Off NBC, the density of organisms was intermediate at all depths. The combined effects of dissolved oxygen concentration and characteristics of water masses affected the distribution of organisms. The faunal patterns were also related with sediment grain size.

Monocyte Phenotype and IFN-γ-Inducible Cytokine Responses Are Associated with Cryptococcal Immune Reconstitution Inflammatory Syndrome

PubMed Central

Meya, David B.; Okurut, Samuel; Zziwa, Godfrey; Cose, Stephen; Bohjanen, Paul R.; Mayanja-Kizza, Harriet; Joloba, Moses; Boulware, David R.; Yukari Manabe, Carol; Wahl, Sharon; Janoff, Edward N.

2017-01-01

A third of adults with AIDS and cryptococcal meningitis (CM) develop immune reconstitution inflammatory syndrome (IRIS) after initiating antiretroviral therapy (ART), which is thought to result from exaggerated inflammatory antigen-specific T cell responses. The contribution of monocytes to the immunopathogenesis of cryptococcal IRIS remains unclear. We compared monocyte subset frequencies and immune responses in HIV-infected Ugandans at time of CM diagnosis (IRIS-Baseline) for those who later developed CM-IRIS, controls who did not develop CM-IRIS (Control-Baseline) at CM-IRIS (IRIS-Event), and for controls at a time point matched for ART duration (Control-Event) to understand the association of monocyte distribution and immune responses with cryptococcal IRIS. At baseline, stimulation with IFN-γ ex vivo induced a higher frequency of TNF-α- and IL-6-producing monocytes among those who later developed IRIS. Among participants who developed IRIS, ex vivo IFN-γ stimulation induced higher frequencies of activated monocytes, IL-6+, TNF-α+ classical, and IL-6+ intermediate monocytes compared with controls. In conclusion, we have demonstrated that monocyte subset phenotype and cytokine responses prior to ART are associated with and may be predictive of CM-IRIS. Larger studies to further delineate innate immunological responses and the efficacy of immunomodulatory therapies during cryptococcal IRIS are warranted. PMID:29371546

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

Cuffey, R.J.; Pachut, J.F.

The Holocene reef-building coral Favia pallida was sampled at 4.5 m depth increments (to 40 m) from two reefs on Enewetak Atoll to examine intraspecific environmental effects. An exposed outer reef was massive and wall-like, whereas a sheltered lagoonal reef grew as a slender pinnacle. Corallite diameter and growth rate, two attributes retrievable in fossil corals, were measured with data partitioned into shallow (<20 m), intermediate (20 to 29 m), and deep-water (>29 m) subsets. Highly significant differences between depth zone populations were found for both corallite diameters and growth rates in analyses of individual and combined reef data sets.more » Canonical variates analyses (CVA) separated populations from depth zones along single, highly significant, functions. Centroids and 95% confidence intervals, calculated from CVA scores of colonies in each population, are widely separated for the lagoon reef and combined data sets. Conversely, populations from shallow and intermediate depths on the outer reef display overlapping confidence bars indicative of more gradational morphologic changes. When CV's were used to classify specimens to groups, misassignments of intermediate depth specimens to shallow or deep-water populations underscored the gradational nature of the environment. Completely intergrading populations of Favia pallida collected from different depths can be morphologically separated into statistically distinct groupings. A stratigraphic succession of such morphotypes might be interpreted as abruptly appearing separate species if sampling were not as uniform, systematic, and detailed as was possible on modern reefs. Analyses of evolutionary patterns must carefully assess potential effects of clinal variation if past evolutionary patterns are to be interpreted correctly.« less

Impact of Consuming Extra-Virgin Olive Oil or Nuts within a Mediterranean Diet on DNA Methylation in Peripheral White Blood Cells within the PREDIMED-Navarra Randomized Controlled Trial: A Role for Dietary Lipids.

PubMed

Arpón, Ana; Milagro, Fermín I; Razquin, Cristina; Corella, Dolores; Estruch, Ramón; Fitó, Montserrat; Marti, Amelia; Martínez-González, Miguel A; Ros, Emilio; Salas-Salvadó, Jordi; Riezu-Boj, José-Ignacio; Martínez, J Alfredo

2017-12-23

DNA methylation could be reversible and mouldable by environmental factors, such as dietary exposures. The objective was to analyse whether an intervention with two Mediterranean diets, one rich in extra-virgin olive oil (MedDiet + EVOO) and the other one in nuts (MedDiet + nuts), was influencing the methylation status of peripheral white blood cells (PWBCs) genes. A subset of 36 representative individuals were selected within the PREvención con DIeta MEDiterránea (PREDIMED-Navarra) trial, with three intervention groups in high cardiovascular risk volunteers: MedDiet + EVOO, MedDiet + nuts, and a low-fat control group. Methylation was assessed at baseline and at five-year follow-up. Ingenuity pathway analysis showed routes with differentially methylated CpG sites (CpGs) related to intermediate metabolism, diabetes, inflammation, and signal transduction. Two CpGs were specifically selected: cg01081346- CPT1B / CHKB-CPT1B and cg17071192- GNAS/GNASAS , being associated with intermediate metabolism. Furthermore, cg01081346 was associated with PUFAs intake, showing a role for specific fatty acids on epigenetic modulation. Specific components of MedDiet, particularly nuts and EVOO, were able to induce methylation changes in several PWBCs genes. These changes may have potential benefits in health; especially those changes in genes related to intermediate metabolism, diabetes, inflammation and signal transduction, which may contribute to explain the role of MedDiet and fat quality on health outcomes.

Impact of Consuming Extra-Virgin Olive Oil or Nuts within a Mediterranean Diet on DNA Methylation in Peripheral White Blood Cells within the PREDIMED-Navarra Randomized Controlled Trial: A Role for Dietary Lipids

PubMed Central

Razquin, Cristina; Estruch, Ramón; Fitó, Montserrat; Martínez-González, Miguel A.; Ros, Emilio

2017-01-01

DNA methylation could be reversible and mouldable by environmental factors, such as dietary exposures. The objective was to analyse whether an intervention with two Mediterranean diets, one rich in extra-virgin olive oil (MedDiet + EVOO) and the other one in nuts (MedDiet + nuts), was influencing the methylation status of peripheral white blood cells (PWBCs) genes. A subset of 36 representative individuals were selected within the PREvención con DIeta MEDiterránea (PREDIMED-Navarra) trial, with three intervention groups in high cardiovascular risk volunteers: MedDiet + EVOO, MedDiet + nuts, and a low-fat control group. Methylation was assessed at baseline and at five-year follow-up. Ingenuity pathway analysis showed routes with differentially methylated CpG sites (CpGs) related to intermediate metabolism, diabetes, inflammation, and signal transduction. Two CpGs were specifically selected: cg01081346–CPT1B/CHKB-CPT1B and cg17071192–GNAS/GNASAS, being associated with intermediate metabolism. Furthermore, cg01081346 was associated with PUFAs intake, showing a role for specific fatty acids on epigenetic modulation. Specific components of MedDiet, particularly nuts and EVOO, were able to induce methylation changes in several PWBCs genes. These changes may have potential benefits in health; especially those changes in genes related to intermediate metabolism, diabetes, inflammation and signal transduction, which may contribute to explain the role of MedDiet and fat quality on health outcomes. PMID:29295516

Hoxa2 Selectively Enhances Meis Binding to Change a Branchial Arch Ground State

PubMed Central

Amin, Shilu; Donaldson, Ian J.; Zannino, Denise A.; Hensman, James; Rattray, Magnus; Losa, Marta; Spitz, François; Ladam, Franck; Sagerström, Charles; Bobola, Nicoletta

2015-01-01

Summary Hox transcription factors (TFs) are essential for vertebrate development, but how these evolutionary conserved proteins function in vivo remains unclear. Because Hox proteins have notoriously low binding specificity, they are believed to bind with cofactors, mainly homeodomain TFs Pbx and Meis, to select their specific targets. We mapped binding of Meis, Pbx, and Hoxa2 in the branchial arches, a series of segments in the developing vertebrate head. Meis occupancy is largely similar in Hox-positive and -negative arches. Hoxa2, which specifies second arch (IIBA) identity, recognizes a subset of Meis prebound sites that contain Hox motifs. Importantly, at these sites Meis binding is strongly increased. This enhanced Meis binding coincides with active enhancers, which are linked to genes highly expressed in the IIBA and regulated by Hoxa2. These findings show that Hoxa2 operates as a tissue-specific cofactor, enhancing Meis binding to specific sites that provide the IIBA with its anatomical identity. PMID:25640223

Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability.

PubMed

Brooks, Marjory B; Turk, James R; Guerrero, Abraham; Narayanan, Padma K; Nolan, John P; Besteman, Elizabeth G; Wilson, Dennis W; Thomas, Roberta A; Fishman, Cindy E; Thompson, Karol L; Ellinger-Ziegelbauer, Heidrun; Pierson, Jennifer B; Paulman, April; Chiang, Alan Y; Schultze, Albert E

2017-01-01

Systemic inflammation co-activates coagulation, which unchecked culminates in a lethal syndrome of multi-organ microvascular thrombosis known as disseminated intravascular coagulation (DIC). We studied an endotoxin-induced inflammatory state in rats to identify biomarkers of hemostatic imbalance favoring hypercoagulability. Intraperitoneal injection of LPS at 15 mg/kg body weight resulted in peripheral leukopenia and widespread neutrophilic sequestration characteristic of an acute systemic inflammatory response. Early indicators of hemostatic pathway activation developed within 4 hours, including increased circulating concentrations of procoagulant extracellular vesicles (EVs), EVs expressing endothelial cell and platelet membrane markers, and high concentration of soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1), and D-dimers. Inflammation persisted throughout the 48-hour observation period; however, increases were found in a subset of serum microRNA (miRNA) that coincided with gradual resolution of hemostatic protein abnormalities and reduction in EV counts. Dose-adjusted LPS treatment in rats provides a time-course model to develop biomarker profiles reflecting procoagulant imbalance and rebalance under inflammatory conditions.

Sequences Associated with Centromere Competency in the Human Genome

PubMed Central

Hayden, Karen E.; Strome, Erin D.; Merrett, Stephanie L.; Lee, Hye-Ran; Rudd, M. Katharine

2013-01-01

Centromeres, the sites of spindle attachment during mitosis and meiosis, are located in specific positions in the human genome, normally coincident with diverse subsets of alpha satellite DNA. While there is strong evidence supporting the association of some subfamilies of alpha satellite with centromere function, the basis for establishing whether a given alpha satellite sequence is or is not designated a functional centromere is unknown, and attempts to understand the role of particular sequence features in establishing centromere identity have been limited by the near identity and repetitive nature of satellite sequences. Utilizing a broadly applicable experimental approach to test sequence competency for centromere specification, we have carried out a genomic and epigenetic functional analysis of endogenous human centromere sequences available in the current human genome assembly. The data support a model in which functionally competent sequences confer an opportunity for centromere specification, integrating genomic and epigenetic signals and promoting the concept of context-dependent centromere inheritance. PMID:23230266

The Southern HII Region Discovery Survey

NASA Astrophysics Data System (ADS)

Wenger, Trey; Miller Dickey, John; Jordan, Christopher; Bania, Thomas M.; Balser, Dana S.; Dawson, Joanne; Anderson, Loren D.; Armentrout, William P.; McClure-Griffiths, Naomi

2016-01-01

HII regions are zones of ionized gas surrounding recently formed high-mass (OB-type) stars. They are among the brightest objects in the sky at radio wavelengths. HII regions provide a useful tool in constraining the Galactic morphological structure, chemical structure, and star formation rate. We describe the Southern HII Region Discovery Survey (SHRDS), an Australia Telescope Compact Array (ATCA) survey that discovered ~80 new HII regions (so far) in the Galactic longitude range 230 degrees to 360 degrees. This project is an extension of the Green Bank Telescope HII Region Discovery Survey (GBT HRDS), Arecibo HRDS, and GBT Widefield Infrared Survey Explorer (WISE) HRDS, which together discovered ~800 new HII regions in the Galactic longitude range -20 degrees to 270 degrees. Similar to those surveys, candidate HII regions were chosen from 20 micron emission (from WISE) coincident with 10 micron (WISE) and 20 cm (SGPS) emission. By using the ATCA to detect radio continuum and radio recombination line emission from a subset of these candidates, we have added to the population of known Galactic HII regions.

Mannose Induces an Endonuclease Responsible for DNA Laddering in Plant Cells

PubMed Central

Stein, Joshua C.; Hansen, Geneviève

1999-01-01

The effect of d-mannose (Man) on plant cells was studied in two different systems: Arabidopsis roots and maize (Zea mays) suspension-cultured cells. In both systems, exposure to d-Man was associated with a subset of features characteristic of apoptosis, as assessed by oligonucleosomal fragmentation and microscopy analysis. Furthermore, d-Man induced the release of cytochrome c from mitochondria. The specificity of d-Man was evaluated by comparing the effects of diastereomers such as l-Man, d-glucose, and d-galactose. Of these treatments, only d-Man caused a reduction in final fresh weight with concomitant oligonucleosomal fragmentation. Man-induced DNA laddering coincided with the activation of a DNase in maize cytosolic extracts and with the appearance of single 35-kD band detected using an in-gel DNase assay. The DNase activity was further confirmed by using covalently closed circular plasmid DNA as a substrate. It appears that d-Man, a safe and readily accessible compound, offers remarkable features for the study of apoptosis in plant cells. PMID:10482662

Intermediate-term earthquake prediction

USGS Publications Warehouse

Knopoff, L.

1990-01-01

The problems in predicting earthquakes have been attacked by phenomenological methods from pre-historic times to the present. The associations of presumed precursors with large earthquakes often have been remarked upon. the difficulty in identifying whether such correlations are due to some chance coincidence or are real precursors is that usually one notes the associations only in the relatively short time intervals before the large events. Only rarely, if ever, is notice taken of whether the presumed precursor is to be found in the rather long intervals that follow large earthquakes, or in fact is absent in these post-earthquake intervals. If there are enough examples, the presumed correlation fails as a precursor in the former case, while in the latter case the precursor would be verified. Unfortunately, the observer is usually not concerned with the 'uniteresting' intervals that have no large earthquakes. 

Analytic model for the long-term evolution of circular Earth satellite orbits including lunar node regression

NASA Astrophysics Data System (ADS)

Zhu, Ting-Lei; Zhao, Chang-Yin; Zhang, Ming-Jiang

2017-04-01

This paper aims to obtain an analytic approximation to the evolution of circular orbits governed by the Earth's J2 and the luni-solar gravitational perturbations. Assuming that the lunar orbital plane coincides with the ecliptic plane, Allan and Cook (Proc. R. Soc. A, Math. Phys. Eng. Sci. 280(1380):97, 1964) derived an analytic solution to the orbital plane evolution of circular orbits. Using their result as an intermediate solution, we establish an approximate analytic model with lunar orbital inclination and its node regression be taken into account. Finally, an approximate analytic expression is derived, which is accurate compared to the numerical results except for the resonant cases when the period of the reference orbit approximately equals the integer multiples (especially 1 or 2 times) of lunar node regression period.

Analytical method for optimal source reduction with monitored natural attenuation in contaminated aquifers

USGS Publications Warehouse

Widdowson, M.A.; Chapelle, F.H.; Brauner, J.S.; ,

2003-01-01

A method is developed for optimizing monitored natural attenuation (MNA) and the reduction in the aqueous source zone concentration (??C) required to meet a site-specific regulatory target concentration. The mathematical model consists of two one-dimensional equations of mass balance for the aqueous phase contaminant, to coincide with up to two distinct zones of transformation, and appropriate boundary and intermediate conditions. The solution is written in terms of zone-dependent Peclet and Damko??hler numbers. The model is illustrated at a chlorinated solvent site where MNA was implemented following source treatment using in-situ chemical oxidation. The results demonstrate that by not taking into account a variable natural attenuation capacity (NAC), a lower target ??C is predicted, resulting in unnecessary source concentration reduction and cost with little benefit to achieving site-specific remediation goals.

Pressure-induced increase of exciton-LO-phonon coupling in a ZnCdSe/ZnSe quantum well

NASA Astrophysics Data System (ADS)

Guo, Z. Z.; Liang, X. X.; Ban, S. L.

2003-07-01

The possibility of pressure-induced increase of exciton-LO-phonon coupling in ZnCdSe/ZnSe quantum wells is studied. The ground state binding energies of the heavy hole excitons are calculated using a variational method with consideration of the electron-phonon interaction and the pressure dependence of the parameters. The results show that for quantum wells with intermediate well width, the exciton binding energy and the LO-phonon energy may coincide in the course of pressure increasing, resulting in the increase of exciton-LO-phonon coupling. It is also found that among the pressure-dependent parameters, the influence of the lattice constant is the most important one. The changes of both the effective masses and the dielectric constants have obvious effects on the exciton binding energy, but their influences are counterbalanced.

Vibrational spectroscopic studies and DFT calculations of 4-aminoantipyrine

NASA Astrophysics Data System (ADS)

Swaminathan, J.; Ramalingam, M.; Sethuraman, V.; Sundaraganesan, N.; Sebastian, S.

2009-08-01

The pyrazole derivative, 4-aminoantipyrine (4AAP), used as an intermediate for the synthesis of pharmaceuticals especially antipyretic and analgesic drugs has been analyzed experimentally and theoretically for its vibrational frequencies. The FTIR and FT Raman spectra of the title compound have been compared with the theoretically computed frequencies invoking the standard 6-311g(d,p) and cc-pVDZ basis sets at DFT level of theory (B3LYP). The harmonic vibrational frequencies at B3LYP/cc-pVDZ after appropriate scaling method seem to coincide satisfactorily with the experimental observations rather than B3LYP/6-311g(d,p) results. The theoretical spectrograms for FT-IR and FT-Raman spectra of 4AAP have been also constructed and compared with the experimental spectra. Additionally, thermodynamic data have also been calculated and discussed.

Inverted micellar intermediates and the transitions between lamellar, cubic, and inverted hexagonal lipid phases. II. Implications for membrane-membrane interactions and membrane fusion.

PubMed Central

Siegel, D P

1986-01-01

Results of a kinetic model of thermotropic L alpha----HII phase transitions are used to predict the types and order-of-magnitude rates of interactions between unilamellar vesicles that can occur by intermediates in the L alpha----HII phase transition. These interactions are: outer monolayer lipid exchange between vesicles; vesicle leakage subsequent to aggregation; and (only in systems with ratios of L alpha and HII phase structural dimensions in a certain range or with unusually large bilayer lateral compressibilities) vesicle fusion with retention of contents. It was previously proposed that inverted micellar structures mediate membrane fusion. These inverted micellar structures are thought to form in all systems with such transitions. However, I show that membrane fusion probably occurs via structures that form from these inverted micellar intermediates, and that fusion should occur in only a sub-set of lipid systems that can adopt the HII phase. For single-component phosphatidylethanolamine (PE) systems with thermotropic L alpha----HII transitions, lipid exchange should be observed starting at temperatures several degrees below TH and at all higher temperatures, where TH is the L alpha----HII transition temperature. At temperatures above TH, the HII phase forms between apposed vesicles, and eventually ruptures them (leakage). In most single-component PE systems, fusion via L alpha----HII transition intermediates should not occur. This is the behavior observed by Bentz, Ellens, Lai, Szoka, et al. in PE vesicle systems. Fusion is likely to occur under circumstances in which multilamellar samples of lipid form the so-called "inverted cubic" or "isotropic" phase. This is as observed in the mono-methyl DOPE system (Ellens, H., J. Bentz, and F. C. Szoka. 1986. Fusion of phosphatidylethanolamine containing liposomes and the mechanism of the L alpha-HII phase transition. Biochemistry. In press.) In lipid systems with L alpha----HII transitions driven by cation binding (e.g., Ca2+-cardiolipin), fusion should be more frequent than in thermotropic systems. PMID:3719075

Coordination of Rad1-Rad10 interactions with Msh2-Msh3, Saw1 and RPA is essential for functional 3' non-homologous tail removal.

PubMed

Eichmiller, Robin; Medina-Rivera, Melisa; DeSanto, Rachel; Minca, Eugen; Kim, Christopher; Holland, Cory; Seol, Ja-Hwan; Schmit, Megan; Oramus, Diane; Smith, Jessica; Gallardo, Ignacio F; Finkelstein, Ilya J; Lee, Sang Eun; Surtees, Jennifer A

2018-06-01

Double strand DNA break repair (DSBR) comprises multiple pathways. A subset of DSBR pathways, including single strand annealing, involve intermediates with 3' non-homologous tails that must be removed to complete repair. In Saccharomyces cerevisiae, Rad1-Rad10 is the structure-specific endonuclease that cleaves the tails in 3' non-homologous tail removal (3' NHTR). Rad1-Rad10 is also an essential component of the nucleotide excision repair (NER) pathway. In both cases, Rad1-Rad10 requires protein partners for recruitment to the relevant DNA intermediate. Msh2-Msh3 and Saw1 recruit Rad1-Rad10 in 3' NHTR; Rad14 recruits Rad1-Rad10 in NER. We created two rad1 separation-of-function alleles, rad1R203A,K205A and rad1R218A; both are defective in 3' NHTR but functional in NER. In vitro, rad1R203A,K205A was impaired at multiple steps in 3' NHTR. The rad1R218A in vivo phenotype resembles that of msh2- or msh3-deleted cells; recruitment of rad1R218A-Rad10 to recombination intermediates is defective. Interactions among rad1R218A-Rad10 and Msh2-Msh3 and Saw1 are altered and rad1R218A-Rad10 interactions with RPA are compromised. We propose a model in which Rad1-Rad10 is recruited and positioned at the recombination intermediate through interactions, between Saw1 and DNA, Rad1-Rad10 and Msh2-Msh3, Saw1 and Msh2-Msh3 and Rad1-Rad10 and RPA. When any of these interactions is altered, 3' NHTR is impaired.

Decreased glycolytic and tricarboxylic acid cycle intermediates coincide with peripheral nervous system oxidative stress in a murine model of type 2 diabetes.

PubMed

Hinder, Lucy M; Vivekanandan-Giri, Anuradha; McLean, Lisa L; Pennathur, Subramaniam; Feldman, Eva L

2013-01-01

Diabetic neuropathy (DN) is the most common complication of diabetes and is characterized by distal-to-proximal loss of peripheral nerve axons. The idea of tissue-specific pathological alterations in energy metabolism in diabetic complications-prone tissues is emerging. Altered nerve metabolism in type 1 diabetes models is observed; however, therapeutic strategies based on these models offer limited efficacy to type 2 diabetic patients with DN. Therefore, understanding how peripheral nerves metabolically adapt to the unique type 2 diabetic environment is critical to develop disease-modifying treatments. In the current study, we utilized targeted liquid chromatography-tandem mass spectrometry (LC/MS/MS) to characterize the glycolytic and tricarboxylic acid (TCA) cycle metabolomes in sural nerve, sciatic nerve, and dorsal root ganglia (DRG) from male type 2 diabetic mice (BKS.Cg-m+/+Lepr(db); db/db) and controls (db/+). We report depletion of glycolytic intermediates in diabetic sural nerve and sciatic nerve (glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate (sural nerve only), 3-phosphoglycerate, 2-phosphoglycerate, phosphoenolpyruvate, and lactate), with no significant changes in DRG. Citrate and isocitrate TCA cycle intermediates were decreased in sural nerve, sciatic nerve, and DRG from diabetic mice. Utilizing LC/electrospray ionization/MS/MS and HPLC methods, we also observed increased protein and lipid oxidation (nitrotyrosine; hydroxyoctadecadienoic acids) in db/db tissue, with a proximal-to-distal increase in oxidative stress, with associated decreased aconitase enzyme activity. We propose a preliminary model, whereby the greater change in metabolomic profile, increase in oxidative stress, and decrease in TCA cycle enzyme activity may cause distal peripheral nerves to rely on truncated TCA cycle metabolism in the type 2 diabetes environment.

Antarctic climate, Southern Ocean circulation patterns, and deep water formation during the Eocene

NASA Astrophysics Data System (ADS)

Huck, Claire E.; van de Flierdt, Tina; Bohaty, Steven M.; Hammond, Samantha J.

2017-07-01

We assess early-to-middle Eocene seawater neodymium (Nd) isotope records from seven Southern Ocean deep-sea drill sites to evaluate the role of Southern Ocean circulation in long-term Cenozoic climate change. Our study sites are strategically located on either side of the Tasman Gateway and are positioned at a range of shallow (<500 m) to intermediate/deep ( 1000-2500 m) paleowater depths. Unradiogenic seawater Nd isotopic compositions, reconstructed from fish teeth at intermediate/deep Indian Ocean pelagic sites (Ocean Drilling Program (ODP) Sites 738 and 757 and Deep Sea Drilling Project (DSDP) Site 264), indicate a dominant Southern Ocean-sourced contribution to regional deep waters (ɛNd(t) = -9.3 ± 1.5). IODP Site U1356 off the coast of Adélie Land, a locus of modern-day Antarctic Bottom Water production, is identified as a site of persistent deep water formation from the early Eocene to the Oligocene. East of the Tasman Gateway an additional local source of intermediate/deep water formation is inferred at ODP Site 277 in the SW Pacific Ocean (ɛNd(t) = -8.7 ± 1.5). Antarctic-proximal shelf sites (ODP Site 1171 and Site U1356) reveal a pronounced erosional event between 49 and 48 Ma, manifested by 2 ɛNd unit negative excursions in seawater chemistry toward the composition of bulk sediments at these sites. This erosional event coincides with the termination of peak global warmth following the Early Eocene Climatic Optimum and is associated with documented cooling across the study region and increased export of Antarctic deep waters, highlighting the complexity and importance of Southern Ocean circulation in the greenhouse climate of the Eocene.

Variation in bull beef quality due to ultimate muscle pH is correlated to endopeptidase and small heat shock protein levels.

PubMed

Pulford, D J; Dobbie, P; Fraga Vazquez, S; Fraser-Smith, E; Frost, D A; Morris, C A

2009-09-01

This study set out to determine if ultimate pH (pH(u)) affected the performance of intracellular small heat shock protein and endopeptidase dynamics in muscle during beef ageing. Longissimus dorsi muscles from 39 Angus or Limousin×Angus bulls were examined to see if pH(u) achieved at 22h post mortem (rigor) affected tenderness and water holding capacity of beef. Samples were segregated into three pH(u) groups termed high (pH>6.3), intermediate (5.73 days post mortem for intermediate pH(u) beef. High levels of alpha β-crystallin (aβC) at 22h post mortem coincided with delayed muscle protein degradation for low pH(u) beef. Our results support the hypothesis that aβC shields myofibrils and buffers against endopeptidase degradation of beef structure during ageing.

Fragment length analysis screening for detection of CEBPA mutations in intermediate-risk karyotype acute myeloid leukemia.

PubMed

Fuster, Oscar; Barragán, Eva; Bolufer, Pascual; Such, Esperanza; Valencia, Ana; Ibáñez, Mariam; Dolz, Sandra; de Juan, Inmaculada; Jiménez, Antonio; Gómez, Maria Teresa; Buño, Ismael; Martínez, Joaquín; Cervera, José; Montesinos, Pau; Moscardó, Federico; Sanz, Miguel Ángel

2012-01-01

During last years, molecular markers have been increased as prognostic factors routinely screened in acute myeloid leukemia (AML). Recently, an increasing interest has been reported in introducing to clinical practice screening for mutations in the CCAAT/enhancer-binding protein α (CEBPA) gene in AML, as it seems to be a good prognostic factor. However, there is no reliable established method for assessing CEBPA mutations during the diagnostic work-up of AMLs. We describe here a straightforward and reliable fragment analysis method based in PCR capillary electrophoresis (PCR-CE) for screening of CEBPA mutations; moreover, we present the results obtained in 151 intermediate-risk karyotype AML patients (aged 16-80 years). The method gave a specificity of 100% and sensitivity of 93% with a lower detection limit of 1-5% for CEBPA mutations. The series found 19 mutations and four polymorphisms in 12 patients, seven of whom (58%) presented two mutations. The overall frequency of CEBPA mutations in AML was 8% (n = 12). CEBPA mutations showed no coincidence with FLT3-ITD or NPM1 mutations. CEBPA mutation predicted better disease-free survival in the group of patients without FLT3-ITD, NPM, or both genes mutated (HR 3.6, IC 95%; 1.0-13.2, p = 0.05) and better overall survival in patients younger than 65 of this group without molecular markers (HR 4.0, IC 95%; 1.0-17.4, p = 0.05). In conclusion, the fragment analysis method based in PCR-CE is a rapid, specific, and sensitive method for CEBPA mutation screening and our results confirm that CEBPA mutations can identify a subgroup of patients with favorable prognosis in AML with intermediate-risk karyotype.

Cluster analysis on a sphere: Application to magnetizations from metasediments of the Jack Hills, Western Australia

NASA Astrophysics Data System (ADS)

Bono, Richard K.; Tarduno, John A.; Dare, Matthew S.; Mitra, Gautam; Cottrell, Rory D.

2018-02-01

Metasediments of the Jack Hills contain the oldest known terrestrial minerals in the form of zircons nearly 4.4 billion years old. Paleointensity data from these zircons provide evidence for a Hadean geodynamo as old as 4.2 billion years old. Given the importance of these zircons for constraining the earliest history of the core, it is vital to understand the fidelity of the zircon record. A fundamental aspect providing context for the preservation of primary magnetic signals is the nature of overprints predicted to have been imparted on rocks of the Jack Hills due to Archean to Proterozoic metamorphic events. To be viable magnetic records of a Hadean geodynamo, zircon magnetization directions should differ from these secondary magnetizations. To evaluate these secondary magnetizations, we report paleomagnetic analyses of a comprehensive sampling of 68 quartzite cobble-sized clasts from the Jack Hills metasediments ∼0.5 to 1.0 km from the Discovery Site (which has yielded the oldest zircons and paleofield estimates). While application of standard paleomagnetic tests suggests that the ensemble of cobble directions cannot be distinguished from those drawn from a random distribution, a new cluster analysis of directions on a sphere and non-parametric resampling approaches reveal significant directions amongst subsets of the data. One, isolated at the lowest temperature analyzed [200 to 300 °C, Declination (Dec.) = 316.8°, Inclination (Inc.) = - 51.1 °] appears to be dominated by the present day field. Another, isolated at higher (but still relatively low unblocking temperatures that we call "intermediate", of ∼350-500 °C, Dec. = 243.8°, Inc. = 9.5°) agrees with a magnetic overprint isolated from the secondary Cr-Fe mica fuchsite isolated from the Jack Hills Discovery site, passing a field test at the 80% confidence level. No evidence is found in our data, or in the data of others collected on similar Jack Hills lithologies, for a widespread 1 Ga remagnetization event. Instead, we interpret the most prevalent secondary magnetization of the quartzite (i.e., intermediate unblocking) and the fuchsite characteristic remanent magnetization to be ∼2.65 Ga in age, coincident with peak metamorphism (as high as ca. 475 °C) of the Jack Hills. The presence of this distinct secondary magnetization, its difference from that recorded by Jack Hills zircons at high unblocking temperatures, and the lack of a dominant remagnetization direction at high unblocking temperatures in the cobble data (the expected result for a primary magnetization), lends further support to the fidelity of the Hadean geomagnetic record. The presence of the secondary magnetization also lends support to the conclusion that most of the Jack Hills metasediments were deposited in the Archean, with only minor reworking and potential tectonic interleaving of Proterozoic components. Overall, the application of the new directional cluster analysis presented here has the potential to reveal magnetic directions in highly scattered data sets, typical of weakly magnetized coarse-grained sedimentary rocks

Global cosmological dynamics for the scalar field representation of the modified Chaplygin gas

NASA Astrophysics Data System (ADS)

Uggla, Claes

2013-09-01

In this paper we investigate the global dynamics for the minimally coupled scalar field representation of the modified Chaplygin gas in the context of flat Friedmann-Lemaître-Robertson Walker cosmology. The tool for doing this is a new set of bounded variables that lead to a regular dynamical system. It is shown that the exact modified Chaplygin gas perfect fluid solution appears as a straight line in the associated phase plane. It is also shown that no other solutions stay close to this solution during their entire temporal evolution, but that there exists an open subset of solutions that stay arbitrarily close during an intermediate time interval, and into the future in the case when the scalar field potential exhibits a global minimum.

Therapies for acute myeloid leukemia: vosaroxin

PubMed Central

Sayar, Hamid; Bashardoust, Parvaneh

2017-01-01

Vosaroxin, a quinolone-derivative chemotherapeutic agent, was considered a promising drug for the treatment of acute myeloid leukemia (AML). Early-stage clinical trials with this agent led to a large randomized double-blind placebo-controlled study of vosaroxin in combination with intermediate-dose cytarabine for the treatment of relapsed or refractory AML. The study demonstrated better complete remission rates with vosaroxin, but there was no statistically significant overall survival benefit in the whole cohort. A subset analysis censoring patients who had undergone allogeneic stem cell transplantation, however, revealed a modest but statistically significant improvement in overall survival particularly among older patients. This article reviews the data available on vosaroxin including clinical trials in AML and offers an analysis of findings of these studies as well as the current status of vosaroxin. PMID:28860803

Therapies for acute myeloid leukemia: vosaroxin.

PubMed

Sayar, Hamid; Bashardoust, Parvaneh

2017-01-01

Vosaroxin, a quinolone-derivative chemotherapeutic agent, was considered a promising drug for the treatment of acute myeloid leukemia (AML). Early-stage clinical trials with this agent led to a large randomized double-blind placebo-controlled study of vosaroxin in combination with intermediate-dose cytarabine for the treatment of relapsed or refractory AML. The study demonstrated better complete remission rates with vosaroxin, but there was no statistically significant overall survival benefit in the whole cohort. A subset analysis censoring patients who had undergone allogeneic stem cell transplantation, however, revealed a modest but statistically significant improvement in overall survival particularly among older patients. This article reviews the data available on vosaroxin including clinical trials in AML and offers an analysis of findings of these studies as well as the current status of vosaroxin.

Integrated Molecular Characterization of Uterine Carcinosarcoma.

PubMed

Cherniack, Andrew D; Shen, Hui; Walter, Vonn; Stewart, Chip; Murray, Bradley A; Bowlby, Reanne; Hu, Xin; Ling, Shiyun; Soslow, Robert A; Broaddus, Russell R; Zuna, Rosemary E; Robertson, Gordon; Laird, Peter W; Kucherlapati, Raju; Mills, Gordon B; Weinstein, John N; Zhang, Jiashan; Akbani, Rehan; Levine, Douglas A

2017-03-13

We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified. Copyright © 2017 Elsevier Inc. All rights reserved.

Interaction of angiogenically stimulated intermediate CD163+ monocytes/macrophages with soft hydrophobic poly(n-butyl acrylate) networks with elastic moduli matched to that of human arteries.

PubMed

Mayer, Anke; Kratz, Karl; Hiebl, Bernhard; Lendlein, Andreas; Jung, Friedrich

2012-03-01

The cell population of peripheral blood monocytes/macrophages (MO) is heterogeneous: The majority of the MO are CD14++ CD16- and named "classical" (= MO1). Furthermore, two other subpopulations were described: CD14++ CD16+ ("intermediate" = MO2) and CD14+ CD16++ ("non-classical" = MO3). It is reported that MO2 possess anti-inflammatory properties and express the MO lineage marker CD163. On a hydrophilic neutrally charged acrylamide-based hydrogel human intermediate (CD14++ CD16+ ), angiogenically stimulated CD163++ monocytes/macrophages (aMO2) maintained a proangiogenic and noninflammatory status for at least 14 days. Here, we explored whether this aMO2 subset adhered to hydrophobic poly(n-butyl acrylate) networks (cPnBA) and also remained in its proangiogenic and noninflammatory status. Because substrate elasticity can impact adherence, morphology, and function of cells, cPnBAs with different Young's modulus (250 and 1100 kPa) were investigated, whereby their elasticity was tailored by variation of the cross-linker content and matched to the elasticity of human arteries. The cPnBAs exhibited similar surface properties (e.g., surface roughness), which were maintained after ethylene oxide sterilization and exposure in serum-free cell culture medium for 18 h at 37°C. aMO2 were seeded on cPnBA samples (1.7 × 10(5) cells/1.33 cm(2) ) in Dulbecco's modified Eagle medium (DMEM high glucose) supplemented with vascular endothelial growth factor 165 (VEGF-A(165) , 10 ng/mL) and fetal calf serum (10 vol%) for 3 and 72 h. On both polymeric samples (n = 3 each), the numbers of adherent cells per unit area were significantly higher (P < 0.01; cPnBA0250: 3 h 13 ± 5 cells/mm(2) , 72 h 234 ± 106 cells/mm(2) ; cPnBA1100: 3 h 14 ± 3 cells/mm(2) , 72 h 198 ± 113 cells/mm(2) ) compared to control cultures (glass, 3 h: 6 ± 3 cells/mm(2) , 72 h: 130 ± 83 cells/mm(2) ) and showed a typically spread morphology. The mRNA expression profile of the aMO2 was not influenced by the substrate elasticity. In the supernatant of aMO2 on cPnBA0250, significantly less VEGF-A(165) product was found than expected based on the mRNA level measured (P < 0.01). Tests with recombinant VEGF-A(165) then demonstrated that significantly more VEGF-A(165) was adhered on cPnBA0250 than on cPnBA1100 (P < 0.01). Seeded on cPnBA, aMO2-unaffected by the elastic moduli of both substrates-seemed to remain in their subset status and secreted VEGF-A(165) without release of proinflammatory cytokines. These in vitro results might indicate that this MO subset can be used as cellular delivery system for proangiogenic and noninflammatory mediators to support the endothelialization of cPnBA. © 2012, Copyright the Authors. Artificial Organs © 2012, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Investigating the limits of PET/CT imaging at very low true count rates and high random fractions in ion-beam therapy monitoring

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

Kurz, Christopher, E-mail: Christopher.Kurz@physik.uni-muenchen.de; Bauer, Julia; Conti, Maurizio

Purpose: External beam radiotherapy with protons and heavier ions enables a tighter conformation of the applied dose to arbitrarily shaped tumor volumes with respect to photons, but is more sensitive to uncertainties in the radiotherapeutic treatment chain. Consequently, an independent verification of the applied treatment is highly desirable. For this purpose, the irradiation-induced β{sup +}-emitter distribution within the patient is detected shortly after irradiation by a commercial full-ring positron emission tomography/x-ray computed tomography (PET/CT) scanner installed next to the treatment rooms at the Heidelberg Ion-Beam Therapy Center (HIT). A major challenge to this approach is posed by the small numbermore » of detected coincidences. This contribution aims at characterizing the performance of the used PET/CT device and identifying the best-performing reconstruction algorithm under the particular statistical conditions of PET-based treatment monitoring. Moreover, this study addresses the impact of radiation background from the intrinsically radioactive lutetium-oxyorthosilicate (LSO)-based detectors at low counts. Methods: The authors have acquired 30 subsequent PET scans of a cylindrical phantom emulating a patientlike activity pattern and spanning the entire patient counting regime in terms of true coincidences and random fractions (RFs). Accuracy and precision of activity quantification, image noise, and geometrical fidelity of the scanner have been investigated for various reconstruction algorithms and settings in order to identify a practical, well-suited reconstruction scheme for PET-based treatment verification. Truncated listmode data have been utilized for separating the effects of small true count numbers and high RFs on the reconstructed images. A corresponding simulation study enabled extending the results to an even wider range of counting statistics and to additionally investigate the impact of scatter coincidences. Eventually, the recommended reconstruction scheme has been applied to exemplary postirradiation patient data-sets. Results: Among the investigated reconstruction options, the overall best results in terms of image noise, activity quantification, and accurate geometrical recovery were achieved using the ordered subset expectation maximization reconstruction algorithm with time-of-flight (TOF) and point-spread function (PSF) information. For this algorithm, reasonably accurate (better than 5%) and precise (uncertainty of the mean activity below 10%) imaging can be provided down to 80 000 true coincidences at 96% RF. Image noise and geometrical fidelity are generally improved for fewer iterations. The main limitation for PET-based treatment monitoring has been identified in the small number of true coincidences, rather than the high intrinsic random background. Application of the optimized reconstruction scheme to patient data-sets results in a 25% − 50% reduced image noise at a comparable activity quantification accuracy and an improved geometrical performance with respect to the formerly used reconstruction scheme at HIT, adopted from nuclear medicine applications. Conclusions: Under the poor statistical conditions in PET-based treatment monitoring, improved results can be achieved by considering PSF and TOF information during image reconstruction and by applying less iterations than in conventional nuclear medicine imaging. Geometrical fidelity and image noise are mainly limited by the low number of true coincidences, not the high LSO-related random background. The retrieved results might also impact other emerging PET applications at low counting statistics.« less

Accumulation of actin in subsets of pioneer growth cone filopodia in response to neural and epithelial guidance cues in situ

PubMed Central

1993-01-01

Directed outgrowth of neural processes must involve transmission of signals from the tips of filopodia to the central region of the growth cone. Here, we report on the distribution and dynamics of one possible element in this process, actin, in live growth cones which are reorienting in response to in situ guidance cues. In grasshopper embryonic limbs, pioneer growth cones respond to at least three types of guidance cues: a limb axis cue, intermediate target cells, and a circumferential band of epithelial cells. With time-lapse imaging of intracellularly injected rhodamine-phalloidin and rhodamine-actin, we monitored the distribution of actin during growth cone responses to these cues. In distal limb regions, accumulation of actin in filopodia and growth cone branches accompanies continued growth, while reduction of actin accompanies withdrawal. Where growth cones are reorienting to intermediate target cells, or along the circumferential epithelial band, actin selectively accumulates in the proximal regions of those filopodia that have contacted target cells or are extending along the band. Actin accumulations can be retrogradely transported along filopodia, and can extend into the central region of the growth cone. These results suggest that regulation and translocation of actin may be a significant element in growth cone steering. PMID:8227150

Transitive homology-guided structural studies lead to discovery of Cro proteins with 40% sequence identity but different folds

PubMed Central

Roessler, Christian G.; Hall, Branwen M.; Anderson, William J.; Ingram, Wendy M.; Roberts, Sue A.; Montfort, William R.; Cordes, Matthew H. J.

2008-01-01

Proteins that share common ancestry may differ in structure and function because of divergent evolution of their amino acid sequences. For a typical diverse protein superfamily, the properties of a few scattered members are known from experiment. A satisfying picture of functional and structural evolution in relation to sequence changes, however, may require characterization of a larger, well chosen subset. Here, we employ a “stepping-stone” method, based on transitive homology, to target sequences intermediate between two related proteins with known divergent properties. We apply the approach to the question of how new protein folds can evolve from preexisting folds and, in particular, to an evolutionary change in secondary structure and oligomeric state in the Cro family of bacteriophage transcription factors, initially identified by sequence-structure comparison of distant homologs from phages P22 and λ. We report crystal structures of two Cro proteins, Xfaso 1 and Pfl 6, with sequences intermediate between those of P22 and λ. The domains show 40% sequence identity but differ by switching of α-helix to β-sheet in a C-terminal region spanning ≈25 residues. Sedimentation analysis also suggests a correlation between helix-to-sheet conversion and strengthened dimerization. PMID:18227506

Spectroscopic and Computational Studies of (µ-Oxo)(µ-1,2-peroxo)diiron(III) Complexes of Relevance to Nonheme Diiron Oxygenase Intermediates

PubMed Central

Fiedler, Adam T.; Shan, Xiaopeng; Mehn, Mark P.; Kaizer, József; Torelli, Stéphane; Frisch, Jonathan R.; Kodera, Masahito; Que, Lawrence

2009-01-01

With the goal of gaining insight into the structures of peroxo intermediates observed for oxygen activating nonheme diiron enzymes, a series of metastable synthetic diiron(III)-peroxo complexes with [FeIII2(µ-O)(µ-1,2-O2)] cores has been characterized by X-ray absorption and resonance Raman spectroscopy. EXAFS analysis shows that this basic core structure gives rise to an Fe-Fe distance of ~3.15 Å; the distance is decreased by 0.1 Å upon introduction of an additional carboxylate bridge. In corresponding resonance Raman studies, vibrations arising from both the Fe-O-Fe and the Fe-O-O-Fe units can be observed. A change in the Fe-Fe distance affects the ν(O-O) mode, as well as the νsym(Fe-O-Fe) and the νasym(Fe-O-Fe) modes. Indeed a linear correlation can be discerned between the ν(O-O) frequency of a complex and its Fe-Fe distance among the subset of complexes with [FeIII2(µ-OR)(µ-1,2-O2)] cores (R = H, alkyl, aryl, or no substituent). These experimental studies are complemented by a normal coordinate analysis and DFT calculations. PMID:18811130

Prevalence of Fasciola in cattle and of its intermediate host Lymnaea snails in central Vietnam.

PubMed

Nguyen, Sam Thi; Nguyen, Duc Tan; Van Nguyen, Thoai; Huynh, Vu Vy; Le, Duc Quyet; Fukuda, Yasuhiro; Nakai, Yutaka

2012-12-01

The aims of this study were to investigate the prevalence of natural Fasciola infections in both the definitive hosts (cattle) and the intermediate hosts (Lymnaea snails) in central Vietnam. A total of 1,075 fecal samples, randomly collected from cattle in Binh Dinh, Khanh Hoa, and Phu Yen provinces, were examined for Fasciola eggs by a sedimentation method. The overall prevalence of Fasciola was 45.3 %. A subset of the animals (235) was also screened for antibodies against Fasciola by an enzyme-linked immunosorbent assay. Overall, 46.3 % of these animals were shedding Fasciola eggs while 87.2 % were Fasciola seropositive. A lower prevalence of Fasciola was observed in calves ≤ 2 years of age (37.6 %) compared to that in cattle >2 years of age (53.7 %) (p < 0.05). The prevalence in the rainy season (50.8 %) was significantly different to that in the dry season (38.1 %) (p < 0.05). Of the 3.269 Lymnaea viridis and 1.128 Lymnaea swinhoei examined, 31 (0.95 %) and seven (0.62 %), respectively, were found to be infected with Fasciola. This appears to be the first epidemiological survey of the prevalence of Fasciola in cattle and snails in these three provinces in central Vietnam.

Intramolecular cyclization of N-phenyl N'(2-chloroethyl)ureas leads to active N-phenyl-4,5-dihydrooxazol-2-amines alkylating β-tubulin Glu198 and prohibitin Asp40.

PubMed

Trzeciakiewicz, Anna; Fortin, Sébastien; Moreau, Emmanuel; C-Gaudreault, René; Lacroix, Jacques; Chambon, Christophe; Communal, Yves; Chezal, Jean-Michel; Miot-Noirault, Elisabeth; Bouchon, Bernadette; Degoul, Françoise

2011-05-01

The cyclization of anticancer drugs into active intermediates has been reported mainly for DNA alkylating molecules including nitrosoureas. We previously defined the original cytotoxic mechanism of anticancerous N-phenyl-N'-(2-chloroethyl)ureas (CEUs) that involves their reactivity towards cellular proteins and not against DNA; two CEU subsets have been shown to alkylate β-tubulin and prohibitin leading to inhibition of cell proliferation by G₂/M or G₁/S cell cycle arrest. In this study, we demonstrated that cyclic derivatives of CEUs, N-phenyl-4,5-dihydrooxazol-2-amines (Oxas) are two- to threefold more active than CEUs and share the same cytotoxic properties in B16F0 melanoma cells. Moreover, the CEU original covalent binding by an ester linkage on β-tubulin Glu198 and prohibitin Asp40 was maintained with Oxas. Surprisingly, we observed that Oxas were spontaneously formed from CEUs in the cell culture medium and were also detected within the cells. Our results suggest that the intramolecular cyclization of CEUs leads to active Oxas that should then be considered as the key intermediates for protein alkylation. These results will be useful for the design of new prodrugs for cancer chemotherapy. Copyright © 2011 Elsevier Inc. All rights reserved.

Sensitivity analysis of simulated SOA loadings using a variance-based statistical approach: SENSITIVITY ANALYSIS OF SOA

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

Shrivastava, Manish; Zhao, Chun; Easter, Richard C.

We investigate the sensitivity of secondary organic aerosol (SOA) loadings simulated by a regional chemical transport model to 7 selected tunable model parameters: 4 involving emissions of anthropogenic and biogenic volatile organic compounds, anthropogenic semi-volatile and intermediate volatility organics (SIVOCs), and NOx, 2 involving dry deposition of SOA precursor gases, and one involving particle-phase transformation of SOA to low volatility. We adopt a quasi-Monte Carlo sampling approach to effectively sample the high-dimensional parameter space, and perform a 250 member ensemble of simulations using a regional model, accounting for some of the latest advances in SOA treatments based on our recentmore » work. We then conduct a variance-based sensitivity analysis using the generalized linear model method to study the responses of simulated SOA loadings to the tunable parameters. Analysis of SOA variance from all 250 simulations shows that the volatility transformation parameter, which controls whether particle-phase transformation of SOA from semi-volatile SOA to non-volatile is on or off, is the dominant contributor to variance of simulated surface-level daytime SOA (65% domain average contribution). We also split the simulations into 2 subsets of 125 each, depending on whether the volatility transformation is turned on/off. For each subset, the SOA variances are dominated by the parameters involving biogenic VOC and anthropogenic SIVOC emissions. Furthermore, biogenic VOC emissions have a larger contribution to SOA variance when the SOA transformation to non-volatile is on, while anthropogenic SIVOC emissions have a larger contribution when the transformation is off. NOx contributes less than 4.3% to SOA variance, and this low contribution is mainly attributed to dominance of intermediate to high NOx conditions throughout the simulated domain. The two parameters related to dry deposition of SOA precursor gases also have very low contributions to SOA variance. This study highlights the large sensitivity of SOA loadings to the particle-phase transformation of SOA volatility, which is neglected in most previous models.« less

Phenotypic and Functional Heterogeneity of Bovine Blood Monocytes

PubMed Central

Hussen, Jamal; Düvel, Anna; Sandra, Olivier; Smith, David; Sheldon, Iain Martin; Zieger, Peter; Schuberth, Hans-Joachim

2013-01-01

Murine and human peripheral blood monocytes are heterogeneous in size, granularity, nuclear morphology, phenotype and function. Whether and how bovine blood monocytes follow this pattern was analyzed in this study. Flow cytometrically, classical monocytes (cM) CD14+ CD16−, intermediate monocytes (intM) CD14+ CD16+ and nonclassical monocytes (ncM) CD14+ CD16+ were identified, with cM being the predominant subset (89%). cM showed a significant lower expression of CD172a, intM expressed the highest level of MHC class II molecules, and ncM were low positive for CD163. Compared to cM and intM, ncM showed a significantly reduced phagocytosis capacity, a significantly reduced generation of reactive oxygen species, and reduced mRNA expression of CXCL8, CXCL1 and IL-1β after LPS stimulation. Based on IL-1β secretion after LPS/ATP stimulation, the inflammasome could be activated in cM and intM, but not in ncM. IFNγ increased the expression of CD16 selectively on cM and induced a shift from cM into intM in vitro. In summary, bovine CD172a-positive mononuclear cells define three monocyte subsets with distinct phenotypic and functional differences. Bovine cM and intM share homologies with their human counterparts, whereas bovine ncM are not inflammatory monocytes. PMID:23967219

A unique proteomic profile on surface IgM ligation in unmutated chronic lymphocytic leukemia

PubMed Central

Perrot, Aurore; Pionneau, Cédric; Nadaud, Sophie; Davi, Frédéric; Leblond, Véronique; Jacob, Frédéric; Merle-Béral, Hélène; Herbrecht, Raoul; Béné, Marie-Christine; Gribben, John G.; Vallat, Laurent

2011-01-01

Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course with 2 extreme subsets: indolent, ZAP70− and mutated immunoglobulin heavy chain gene (M-CLL); and aggressive, ZAP70+ and unmutated immunoglobulin heavy chain (UM-CLL). Given the long-term suspicion of antigenic stimulation as a primum movens in the disease, the role of the B-cell receptor has been extensively studied in various experimental settings; albeit scarcely in a comparative dynamic proteomic approach. Here we use a quantitative 2-dimensional fluorescence difference gel electrophoresis technology to compare 48 proteomic profiles of the 2 CLL subsets before and after anti-IgM ligation. Differentially expressed proteins were subsequently identified by mass spectrometry. We show that unstimulated M- and UM-CLL cells display distinct proteomic profiles. Furthermore, anti-IgM stimulation induces a specific proteomic response, more pronounced in the more aggressive CLL. Statistical analyses demonstrate several significant protein variations according to stimulation conditions. Finally, we identify an intermediate form of M-CLL cells, with an indolent profile (ZAP70−) but sharing aggressive proteomic profiles alike UM-CLL cells. Collectively, this first quantitative and dynamic proteome analysis of CLL further dissects the complex molecular pathway after B-cell receptor stimulation and depicts distinct proteomic profiles, which could lead to novel molecular stratification of the disease. PMID:21602524

Subcomplexes of Ancestral Respiratory Complex I Subunits Rapidly Turn Over in Vivo as Productive Assembly Intermediates in Arabidopsis*

PubMed Central

Li, Lei; Nelson, Clark J.; Carrie, Chris; Gawryluk, Ryan M. R.; Solheim, Cory; Gray, Michael W.; Whelan, James; Millar, A. Harvey

2013-01-01

Subcomplexes of mitochondrial respiratory complex I (CI; EC 1.6.5.3) are shown to turn over in vivo, and we propose a role in an ancestral assembly pathway. By progressively labeling Arabidopsis cell cultures with 15N and isolating mitochondria, we have identified CI subcomplexes through differences in 15N incorporation into their protein subunits. The 200-kDa subcomplex, containing the ancestral γ-carbonic anhydrase (γ-CA), γ-carbonic anhydrase-like, and 20.9-kDa subunits, had a significantly higher turnover rate than intact CI or CI+CIII2. In vitro import of precursors for these CI subunits demonstrated rapid generation of subcomplexes and revealed that their specific abundance varied when different ancestral subunits were imported. Time course studies of precursor import showed the further assembly of these subcomplexes into CI and CI+CIII2, indicating that the subcomplexes are productive intermediates of assembly. The strong transient incorporation of new subunits into the 200-kDa subcomplex in a γ-CA mutant is consistent with this subcomplex being a key initiator of CI assembly in plants. This evidence alongside the pattern of coincident occurrence of genes encoding these particular proteins broadly in eukaryotes, except for opisthokonts, provides a framework for the evolutionary conservation of these accessory subunits and evidence of their function in ancestral CI assembly. PMID:23271729

E2/M1 mixing ratios in transitions from the gamma vibrational bands to the ground state rotational bands of 102, 104, 106, 108Mo, 108, 110, 112Ru, and 112, 114, 116Pd

NASA Astrophysics Data System (ADS)

Eldridge, J. M.; Fenker, B.; Hamilton, J. H.; Goodin, C.; Zachary, C. J.; Wang, E.; Ramayya, A. V.; Daniel, A. V.; Ter-Akopian, G. M.; Oganessian, Yu. Ts.; Luo, Y. X.; Rasmussen, J. O.; Zhu, S. J.

2018-02-01

E2/ M1 mixing ratios have been measured for transitions from states in the γ vibrational bands ( I+_{γ}) to states in the ground state bands (I+ or [I-1]+) of the neutron rich, even-even, deformed isotopes, 102, 104, 106, 108Mo, 108, 110, 112Ru, and 112, 114, 116Pd, including from states as high as 9+_{γ}. These measurements were done using the GAMMASPHERE detector array, which, at the time of the experiment, had 101 working HPGe detectors, arranged at 64 different angles. A 62 μCi source of 252Cf was placed inside GAMMASPHERE yielding 5.7× 10^{11} γ-γ-γ and higher coincidence events. The angular correlations between the transitions from the γ-bands to the ground bands, and the pure E2 transitions within the ground band were then measured. These angular correlations yielded the mixing ratios, demonstrating that these transitions are pure or nearly pure E2, in agreement with theory. In order to correct for possible attenuation due to the lifetime of the intermediate state in these correlations, the g-factors of the intermediate states needed to be known. Therefore, the g-factors of the 2+ states in the ground state band have been measured.

Electron and donor-impurity-related Raman scattering and Raman gain in triangular quantum dots under an applied electric field

NASA Astrophysics Data System (ADS)

Tiutiunnyk, Anton; Akimov, Volodymyr; Tulupenko, Viktor; Mora-Ramos, Miguel E.; Kasapoglu, Esin; Morales, Alvaro L.; Duque, Carlos Alberto

2016-04-01

The differential cross-section of electron Raman scattering and the Raman gain are calculated and analysed in the case of prismatic quantum dots with equilateral triangle base shape. The study takes into account their dependencies on the size of the triangle, the influence of externally applied electric field as well as the presence of an ionized donor center located at the triangle's orthocenter. The calculations are made within the effective mass and parabolic band approximations, with a diagonalization scheme being applied to obtain the eigenfunctions and eigenvalues of the x- y Hamiltonian. The incident and secondary (scattered) radiation have been considered linearly-polarized along the y-direction, coinciding with the direction of the applied electric field. For the case with an impurity center, Raman scattering with the intermediate state energy below the initial state one has been found to show maximum differential cross-section more than by an order of magnitude bigger than that resulting from the scheme with lower intermediate state energy. The Raman gain has maximum magnitude around 35 nm dot size and electric field of 40 kV/cm for the case without impurity and at maximum considered values of the input parameters for the case with impurity. Values of Raman gain of the order of up to 104cm-1 are predicted in both cases.

Examining shifts in zooplankton community as a response of environmental change in Lakes

NASA Astrophysics Data System (ADS)

Ghadouani, Anas; Mines, Conor; Legendre, Pierre; Yan, Norman

2014-05-01

We examined 20 years of zooplankton samples from Harp Lake for shifts in zooplankton variability following invasion by zooplankton predator Bythotrephes longimanus, using organism body size—as measured at high resolution by Laser Optical Plankton Counter (LOPC)—as the primary metric of investigation. A period of transitory high variability in the 2yr post-invasion was observed for both body size compositional variability and aggregate variability metrics, with both measures of variability shifting from low or intermediate to high variability immediately following invasion, before shifting again to intermediate variability, 2 yr post-invasion. Aggregate and compositional variability dynamics were also considered in combination over the study period, revealing that the period of transitory high variability coincided with a shift from a community-wide stasis variability pattern to one of asynchrony, before a shift back to stasis 2 yr post-invasion. These dynamics were related to changes in the significant zooplankton species within the Harp Lake community over the pre- and post- invasion periods, and are likely to be indicative of changes in the stability in the zooplankton community following invasion by Bythotrephes. The dual consideration of aggregate and compositional variability as measured by LOPC was found to provide a valuable means to assess the ecological effects of biological invasion on zooplankton communities as a whole, extending our knowledge of the effects of invasion beyond that already revealed through more traditional taxonomic investigation.

Urinary Schistosomiasis in Urban and Semi-Urban Communities in South-Eastern Nigeria

PubMed Central

OKEKE, Ogochukwu Caroline; UBACHUKWU, Patience Obiageli

2013-01-01

Background In view of the massive rural-to-urban migration in Nigeria, investigations on transmission of urinary schistosomiasis were carried out in urban and semi-urban communities in Nike Lake area of Enugu State, Nigeria. Methods Urine samples of school children were tested for micro-haematuria using reagent strips followed by microscopic examination for Schistosoma haematobium eggs. Water contact sites were also identified and sampled for snails. Results The overall prevalence of S. haematobium eggs in school children was 4.64%. The mean intensity of infection was 1.14 ± 0.41 eggs/10ml urine. Males had insignificantly higher prevalence and intensity of S. haematobium infection than females. The youngest age group (4-7 years) had no infection. The prevalence of micro-haematuria (6.2%) was higher than that of microscopy, and this correlated positively with prevalence (r = 0.65, P < 0.01) and intensity (r = 0.50, P < 0.01) of the infection. Potential intermediate host of human shistosome collected were: Bulinus globosus, B. senegalensis and Biomphalaria pfeifferi. However, only B. globosus shed cercariae of S. haematobium, with a snail infection rate of 0.73%. Transmission was in the dry season coinciding with the drying of wells. Conclusion The results revealed that urinary schistosomiasis is prevalent, and that B. globosus and not B. truncatus as previously reported is the main intermediate host of urinary schistosomiasis in this part of Enugu State. PMID:24454442

Urinary schistosomiasis in urban and semi-urban communities in South-eastern Nigeria.

PubMed

Okeke, Ogochukwu Caroline; Ubachukwu, Patience Obiageli

2013-07-01

In view of the massive rural-to-urban migration in Nigeria, investigations on transmission of urinary schistosomiasis were carried out in urban and semi-urban communities in Nike Lake area of Enugu State, Nigeria. Urine samples of school children were tested for micro-haematuria using reagent strips followed by microscopic examination for Schistosoma haematobium eggs. Water contact sites were also identified and sampled for snails. The overall prevalence of S. haematobium eggs in school children was 4.64%. The mean intensity of infection was 1.14 ± 0.41 eggs/10ml urine. Males had insignificantly higher prevalence and intensity of S. haematobium infection than females. The youngest age group (4-7 years) had no infection. The prevalence of micro-haematuria (6.2%) was higher than that of microscopy, and this correlated positively with prevalence (r = 0.65, P < 0.01) and intensity (r = 0.50, P < 0.01) of the infection. Potential intermediate host of human shistosome collected were: Bulinus globosus, B. senegalensis and Biomphalaria pfeifferi. However, only B. globosus shed cercariae of S. haematobium, with a snail infection rate of 0.73%. Transmission was in the dry season coinciding with the drying of wells. The results revealed that urinary schistosomiasis is prevalent, and that B. globosus and not B. truncatus as previously reported is the main intermediate host of urinary schistosomiasis in this part of Enugu State.

Intermediate-energy inverse-kinematics one-proton pickup reactions on neutron-deficient fp-shell nuclei

NASA Astrophysics Data System (ADS)

McDaniel, S.; Gade, A.; Tostevin, J. A.; Baugher, T.; Bazin, D.; Brown, B. A.; Cook, J. M.; Glasmacher, T.; Grinyer, G. F.; Ratkiewicz, A.; Weisshaar, D.

2012-01-01

Background: Thick-target-induced nucleon-adding transfer reactions onto energetic rare-isotope beams are an emerging spectroscopic tool. Their sensitivity to single-particle structure complements one-nucleon removal reaction capabilities in the quest to reveal the evolution of nuclear shell structure in very exotic nuclei. Purpose: Our purpose is to add intermediate-energy, carbon-target-induced one-proton pickup reactions to the arsenal of γ-ray-tagged direct reactions applicable in the regime of low beam intensities and to apply these for the first time to fp-shell nuclei. Methods: Inclusive and partial cross sections were measured for the 12C(48Cr,49Mn+γ)X and 12C(50Fe,51Co+γ)X proton pickup reactions at 56.7 and 61.2 MeV/nucleon, respectively, using coincident particle-γ spectroscopy at the National Superconducting Cyclotron Laboratory. The results are compared to reaction theory calculations using fp-shell-model nuclear structure input. For comparison with our previous work, the same reactions were measured on 9Be targets. Results: The measured partial cross sections confirm the specific population pattern predicted by theory, with pickup into high-ℓ orbitals being strongly favored, driven by linear and angular momentum matching. Conclusion: Carbon-target-induced pickup reactions are well suited, in the regime of modest beam intensity, to study the evolution of nuclear structure, with specific sensitivities that are well described by theory.

Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

PubMed Central

Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.; Svoboda, Kurt R.

2015-01-01

Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMN). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30µM). Previous work showed that the paralytic mutant zebrafish known as sofa potato, exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. PMID:25668718

Effects of streptozotocin-induced diabetes on bladder and erectile (dys)function in the same rat in vivo.

PubMed

Christ, George J; Hsieh, Yi; Zhao, Weixin; Schenk, Gregory; Venkateswarlu, Karicheti; Wang, Hong-Zhan; Tar, Moses T; Melman, Arnold

2006-05-01

To establish the methods, feasibility and utility of evaluating the impact of diabetes on bladder and erectile function in the same rat, as more than half of diabetic patients have bladder dysfunction, and half of diabetic men have erectile dysfunction, but the severity of coincident disease has not been rigorously assessed. In all, 16 F-344 rats had diabetes induced by streptozotocin (STZ), and were divided into insulin-treated (five) and untreated (11), and compared with age-matched controls (10), all assessed in parallel. All STZ rats were diabetic for 8-11 weeks. Cystometric studies were conducted on all rats, with cavernosometric studies conducted on a subset of rats. There were insulin-reversible increases in the following cystometric variables; bladder weight, bladder capacity, micturition volume, residual volume, micturition pressure and spontaneous activity (P < 0.05, in all, one-way analysis of variance, anova). Cavernosometry showed a diabetes-related, insulin-reversible decline in the cavernosal nerve-stimulated intracavernosal pressure (ICP) response at all levels of current stimulation (P < 0.05, in all one-way anova). Plotting erectile capacity (i.e. ICP) against bladder capacity showed no correlation between the extent of the decline in erectile capacity and the magnitude of the increase in bladder capacity. These studies extend previous work to indicate that the extent of diabetes-related bladder and erectile dysfunction can vary in the same rat. As such, these findings highlight the importance of evaluating the impact of diabetes on multiple organ systems in the lower urinary tract. Future studies using this model system should lead to a better understanding of the initiation, development, progression and coincidence of these common diabetic complications.

Cellular Trafficking of Phospholamban and Formation of Functional Sarcoplasmic Reticulum During Myocyte DIfferentiation

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

Stenoien, David L.; Knyushko, Tatyana V.; Londono, Monica P.

2007-06-01

The sarco/endoplasmic reticulum Ca-ATPase (SERCA) family members are transmembrane proteins that play an essential role in regulating intracellular calcium levels. Phospholamban (PLB), a 52 amino acid phosphoprotein, regulates SERCA activity in adult heart and skeletal muscle. Using the C2C12 myocyte cell line, we find endogenous PLB constitutively expressed in both myoblasts and myotubes, whereas SERCA expression coincides with activation of the differentiation program. PLB has a punctuate distribution in myoblasts changing to a reticular distribution in myotubes where it colocalizes with SERCAs. To examine the distribution and dynamics of PLB and SERCA, we expressed fluorescent fusion proteins (GFP, CFP, andmore » YFP) of PLB and SERCA in myoblasts. Coexpressed PLB and SERCA localize to distinct cellular compartments in myoblasts but begin to colocalize as cells differentiate. Fluorescence Recovery After Photobleaching (FRAP) studies show different recovery patterns for each protein in myoblasts confirming their localization to distinct compartments. To extend these studies, we created stable cell lines expressing O6-alkylguanine-DNA alkyltransferase (AGT) fusions with PLB or SERCA to track their localization as myocytes differentiate. These experiments demonstrate that PLB localizes to punctate vesicles in myoblasts and adopts a reticular distribution that coincides with SERCA distribution after differentiation. Colocalization experiments indicate that a subset of PLB in myoblasts colocalizes with endosomes, Golgi, and the plasma membrane however PLB also localizes to other, as yet unidentified vesicles. Our results indicate that differentiation plays a critical role in regulating PLB distribution to ensure its colocalization within the same cellular compartment as SERCA in differentiated cells. The presence and altered distribution of PLB in undifferentiated myoblasts raises the possibility that this protein has additional functions distinct from SERCA regulation.« less

Diversity of olfactomedin proteins in the sea urchin.

PubMed

Hillier, Brian J; Moy, Gary W; Vacquier, Victor D

2007-06-01

Olfactomedin (OLF) domain proteins maintain extracellular protein-protein interactions in diverse phyla. Only one OLF family member, amassin-1, has been described from the sea urchin Strongylocentrotus purpuratus, a basal invertebrate deuterostome. Amassin-1 mediates intercellular adhesion of coelomocytes (immunocytes). Here we describe the protein structural features of four additional OLF proteins, the total for the genome being five. Phylogenetically, four of these proteins (the amassins) form a subgroup among previously identified OLF proteins. The fifth OLF protein is within the colmedin subfamily and contains a type II transmembrane domain, collagen repeats, and an OLF domain. Sea urchin OLF proteins represent an intermediate diversification between protostomes and vertebrates. Transcripts of all five OLF family members are in coelomocytes and adult radial nerve tissue. Transcripts for some OLF proteins increase during late larval stages. Transcript levels for amassin-1 increase 1,000,000-fold, coinciding with formation of the adult urchin rudiment within the larval body.

[Age structure and dynamics of Quercus wutaishanica population in Lingkong Mountain of Shanxi Province, China].

PubMed

Zhang, Jie; Shangguan, Tie-Liang; Duan, Yi-Hao; Guo, Wei; Liu, Wei-Hua; Guo, Dong-Gang

2014-11-01

Using the plant survivorship theory, the age structure, and the relationship between tree height and diameter (DBH) of Quercus wutaishanica population in Lingkong Mountain were analyzed, and the static life table was compiled and the survival curve plotted. The shuttle shape in age structure of Q. wutaishanica population suggested its temporal stability. The linear regression significantly fitted the positive correlation between tree height and DBH. The maximal life expectancy was observed among the trees beyond the age of the highest mortality and coincided with the lowest point of mortality density, suggesting the strong vitality of the seedlings and young trees that survived in the natural selection and intraspecific competition. The population stability of the Q. wutaishanica population was characterized by the Deevey-II of the survival curve. The dynamic pattern was characterized by the recession in the early phase, growth in the intermediate phase, and stability in the latter phase.

Dark energy in the dark ages

NASA Astrophysics Data System (ADS)

Linder, Eric V.

2006-08-01

Non-negligible dark energy density at high redshifts would indicate dark energy physics distinct from a cosmological constant or "reasonable" canonical scalar fields. Such dark energy can be constrained tightly through investigation of the growth of structure, with limits of ≲2% of total energy density at z ≫ 1 for many models. Intermediate dark energy can have effects distinct from its energy density; the dark ages acceleration can be constrained to last less than 5% of a Hubble e-fold time, exacerbating the coincidence problem. Both the total linear growth, or equivalently σ8, and the shape and evolution of the nonlinear mass power spectrum for z < 2 (using the Linder-White nonlinear mapping prescription) provide important windows. Probes of growth, such as weak gravitational lensing, can interact with supernovae and CMB distance measurements to scan dark energy behavior over the entire range z = 0-1100.

Radial transport of radiation belt electrons in kinetic field-line resonances

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

Chaston, Christopher C.; Bonnell, J. W.; Wygant, J. R.

A representative case study from the Van Allen Probes during a geomagnetic storm recovery phase reveals enhanced electron fluxes at intermediate pitch angles over energies from ~100 keV to 5 MeV coincident with broadband low-frequency electromagnetic waves. The statistical properties of these waves are used to build a model for radial diffusion via drift-bounce resonances in kinetic Alfvén eigenmodes/kinetic field-line resonances. Estimated diffusion coefficients indicate timescales for radial transport on the order of hours in storm time events at energies from <100 keV to MeVs over equatorial pitch angles from the edge of the loss cone to nearly perpendicular tomore » the geomagnetic field. In conclusion, the correlation of kinetic resonances with electron depletions and enhancements during storm main phase and recovery, and the rapid diffusion these waves drive, suggests that they may modulate the outer radiation belt.« less

Localizing the Position of an Ultraluminous X-ray Flare in an Extragalactic Globular Cluster

NASA Astrophysics Data System (ADS)

Irwin, Jimmy

2017-09-01

X-ray timing analysis has revealed two extragalactic sources that flare well above L_Edd for a stellar-mass BH by factors of >100 on time scales of less than a minute, joining only SGRs/AXPs in this category. One of these flares is coincident with the massive globular cluster/ultracompact dwarf galaxy of the elliptical galaxy NGC5128 known as HGHH-C21, which has a resolvable half-light radius of 0.4". Previous observations of the flare were far off-axis where the Chandra PSF was quite large, precluding an accurate position determination of the flare source within HHGH-C21. We propose an 80 ksec ACIS-S on-axis observation of the flare to determine the flare's position within HHGH-C21 to <0.2" uncertainty to distinguish between intermediate-mass BH and exotic accretion mechanism scenarios.

Radial transport of radiation belt electrons in kinetic field-line resonances

DOE PAGES

Chaston, Christopher C.; Bonnell, J. W.; Wygant, J. R.; ...

2017-07-25

A representative case study from the Van Allen Probes during a geomagnetic storm recovery phase reveals enhanced electron fluxes at intermediate pitch angles over energies from ~100 keV to 5 MeV coincident with broadband low-frequency electromagnetic waves. The statistical properties of these waves are used to build a model for radial diffusion via drift-bounce resonances in kinetic Alfvén eigenmodes/kinetic field-line resonances. Estimated diffusion coefficients indicate timescales for radial transport on the order of hours in storm time events at energies from <100 keV to MeVs over equatorial pitch angles from the edge of the loss cone to nearly perpendicular tomore » the geomagnetic field. In conclusion, the correlation of kinetic resonances with electron depletions and enhancements during storm main phase and recovery, and the rapid diffusion these waves drive, suggests that they may modulate the outer radiation belt.« less

Dynamical behavior in f (T, TG) cosmology

NASA Astrophysics Data System (ADS)

Kofinas, Georgios; Leon, Genly; Saridakis, Emmanuel N.

2014-09-01

The f(T,{{T}_{G}}) class of gravitational modification, based on the quadratic torsion scalar T as well as on the new quartic torsion scalar TG, which is the teleparallel equivalent of the Gauss-Bonnet term, is a novel theory, different from both f (T) and f(R,G) ones. We perform a detailed dynamical analysis of a spatially flat universe governed by the simplest non-trivial model of f(T,{{T}_{G}}) gravity which does not introduce a new mass scale. We find that the universe can result in dark-energy dominated, quintessence-like, cosmological-constant-like, or phantom-like solutions, according to the parameter choices. Additionally, it may result in a dark energy-dark matter scaling solution; thus it can alleviate the coincidence problem. Finally, the analysis ‘at infinity’ reveals that the universe may exhibit future, past, or intermediate singularities, depending on the parameters.

Spatial Extent of Charge Repulsion Regulates Assembly Pathways for Lysozyme Amyloid Fibrils

PubMed Central

Hill, Shannon E.; Miti, Tatiana; Richmond, Tyson; Muschol, Martin

2011-01-01

Formation of large protein fibrils with a characteristic cross β-sheet architecture is the key indicator for a wide variety of systemic and neurodegenerative amyloid diseases. Recent experiments have strongly implicated oligomeric intermediates, transiently formed during fibril assembly, as critical contributors to cellular toxicity in amyloid diseases. At the same time, amyloid fibril assembly can proceed along different assembly pathways that might or might not involve such oligomeric intermediates. Elucidating the mechanisms that determine whether fibril formation proceeds along non-oligomeric or oligomeric pathways, therefore, is important not just for understanding amyloid fibril assembly at the molecular level but also for developing new targets for intervening with fibril formation. We have investigated fibril formation by hen egg white lysozyme, an enzyme for which human variants underlie non-neuropathic amyloidosis. Using a combination of static and dynamic light scattering, atomic force microscopy and circular dichroism, we find that amyloidogenic lysozyme monomers switch between three different assembly pathways: from monomeric to oligomeric fibril assembly and, eventually, disordered precipitation as the ionic strength of the solution increases. Fibril assembly only occurred under conditions of net repulsion among the amyloidogenic monomers while net attraction caused precipitation. The transition from monomeric to oligomeric fibril assembly, in turn, occurred as salt-mediated charge screening reduced repulsion among individual charged residues on the same monomer. We suggest a model of amyloid fibril formation in which repulsive charge interactions are a prerequisite for ordered fibril assembly. Furthermore, the spatial extent of non-specific charge screening selects between monomeric and oligomeric assembly pathways by affecting which subset of denatured states can form suitable intermolecular bonds and by altering the energetic and entropic requirements for the initial intermediates emerging along the monomeric vs. oligomeric assembly path. PMID:21483680

Combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) prospective study. Rationale and design.

PubMed

Kennedy, Mark W; Fabris, Enrico; Ijsselmuiden, Alexander J; Nef, Holger; Reith, Sebastian; Escaned, Javier; Alfonso, Fernando; van Royen, Niels; Wojakowski, Wojtek; Witkowski, Adam; Indolfi, Ciro; Ottervanger, Jan Paul; Suryapranata, Harry; Kedhi, Elvin

2016-10-10

Fractional flow reserve (FFR) is a widely used tool for the identification of ischaemia-generating stenoses and to guide decisions on coronary revascularisation. However, the safety of FFR-based decisions in high-risk subsets, such as patients with Diabetes Mellitus (DM) or vulnerable stenoses presenting thin-cap fibro-atheroma (TCFA), is unknown. This study will examine the impact of optical coherence tomography (OCT) plaque morphological assessment and the identification of TCFA, in combination with FFR to better predict clinical outcomes in DM patients. COMBINE (OCT-FFR) is a prospective, multi-centre study investigating the natural history of DM patients with ≥1 angiographically intermediate target lesion in three subgroups of patients; patients with FFR negative lesions without TCFA (group A) and patients with FFR negative lesions with TCFA (group B) as detected by OCT and to compare these two groups with each other, as well as to a third group with FFR-positive, PCI-treated intermediate lesions (group C). The study hypothesis is that DM patients with TCFA (group B) have a worse outcome than those without TCFA (group A) and also when compared to those patients with lesions FFR ≤0.80 who underwent complete revascularisation. The primary endpoint is the incidence of target lesion major adverse cardiac events (MACE); a composite of cardiac death, myocardial infarction or rehospitalisation for unstable/progressive angina in group B vs. group A. COMBINE (OCT-FFR) is the first prospective study to examine whether the addition of OCT plaque morphological evaluation to FFR haemodynamic assessment of intermediate lesions in DM patients will better predict MACE and possibly lead to new revascularisation strategies. Trial Registration Netherlands Trial Register: NTR5376.

Childhood Hodgkin International Prognostic Score (CHIPS) Predicts event-free survival in Hodgkin Lymphoma: A Report from the Children’s Oncology Group

PubMed Central

Schwartz, Cindy L.; Chen, Lu; McCarten, Kathleen; Wolden, Suzanne; Constine, Louis S.; Hutchison, Robert E.; de Alarcon, Pedro A.; Keller, Frank G.; Kelly, Kara M.; Trippet, Tanya A.; Voss, Stephan D.; Friedman, Debra L.

2017-01-01

Background Early response to initial chemotherapy in Hodgkin lymphoma (HL) measured by computed tomography (CT) and/or positron emission tomography (PET) after two to three cycles of chemotherapy may inform therapeutic decisions. Risk stratification at diagnosis could, however, allow earlier and potentially more efficacious treatment modifications. Patients and Methods We developed a predictive model for event-free survival (EFS) in pediatric/adolescent HL using clinical data known at diagnosis from 1103 intermediate-risk HL patients treated on Children’s Oncology Group protocol AHOD0031 with doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC) chemotherapy and radiation. Independent predictors of EFS were identified and used to develop and validate a prognostic score (Childhood Hodgkin International Prognostic Score [CHIPS]). A training cohort was randomly selected to include approximately half of the overall cohort, with the remainder forming the validation cohort. Results Stage 4 disease, large mediastinal mass, albumin (<3.5), and fever were independent predictors of EFS that were each assigned one point in the CHIPS. Four-year EFS was 93.1% for patients with CHIPS = 0, 88.5% for patients with CHIPS = 1, 77.6% for patients with CHIPS = 2, and 69.2% for patients with CHIPS = 3. Conclusions CHIPS was highly predictive of EFS, identifying a subset (with CHIPS 2 or 3) that comprises 27% of intermediate-risk patients who have a 4-year EFS of <80% and who may benefit from early therapeutic augmentation. Furthermore, CHIPS identified higher risk patients who were not identified by early PET or CT response. CHIPS is a robust and inexpensive approach to predicting risk in patients with intermediate-risk HL that may improve ability to tailor therapy to risk factors known at diagnosis. PMID:27786406

Childhood Hodgkin International Prognostic Score (CHIPS) Predicts event-free survival in Hodgkin Lymphoma: A Report from the Children's Oncology Group.

PubMed

Schwartz, Cindy L; Chen, Lu; McCarten, Kathleen; Wolden, Suzanne; Constine, Louis S; Hutchison, Robert E; de Alarcon, Pedro A; Keller, Frank G; Kelly, Kara M; Trippet, Tanya A; Voss, Stephan D; Friedman, Debra L

2017-04-01

Early response to initial chemotherapy in Hodgkin lymphoma (HL) measured by computed tomography (CT) and/or positron emission tomography (PET) after two to three cycles of chemotherapy may inform therapeutic decisions. Risk stratification at diagnosis could, however, allow earlier and potentially more efficacious treatment modifications. We developed a predictive model for event-free survival (EFS) in pediatric/adolescent HL using clinical data known at diagnosis from 1103 intermediate-risk HL patients treated on Children's Oncology Group protocol AHOD0031 with doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC) chemotherapy and radiation. Independent predictors of EFS were identified and used to develop and validate a prognostic score (Childhood Hodgkin International Prognostic Score [CHIPS]). A training cohort was randomly selected to include approximately half of the overall cohort, with the remainder forming the validation cohort. Stage 4 disease, large mediastinal mass, albumin (<3.5), and fever were independent predictors of EFS that were each assigned one point in the CHIPS.  Four-year EFS was 93.1% for patients with CHIPS = 0, 88.5% for patients with CHIPS = 1, 77.6% for patients with CHIPS = 2, and 69.2% for patients with CHIPS = 3. CHIPS was highly predictive of EFS, identifying a subset (with CHIPS 2 or 3) that comprises 27% of intermediate-risk patients who have a 4-year EFS of <80% and who may benefit from early therapeutic augmentation.  Furthermore, CHIPS identified higher risk patients who were not identified by early PET or CT response. CHIPS is a robust and inexpensive approach to predicting risk in patients with intermediate-risk HL that may improve ability to tailor therapy to risk factors known at diagnosis. © 2016 Wiley Periodicals, Inc.

Ground-water resources of Flagler County, Florida

USGS Publications Warehouse

Navoy, A.S.; Bradner, L.A.

1987-01-01

Groundwater is the only significant source of potable water in Flagler County. Usable water occurs in the Upper Floridan aquifer, the intermediate population is expected to place stresses on the water resources of the county. Although rainfall averages almost 50 in/yr, most of the water leaves as evapotranspiration and streamflow. Less than 1 in/yr recharge may be occurring to the Upper Floridan aquifer, the highest yielding aquifer. The Upper Floridan aquifer consists of the Avon Park Formation, the Ocala Limestone, and the basal dolomitic limestone of the Hawthorne. Use of the Upper Floridan aquifer for public water supply is limited in most of the county because it contains marginally potable or brackish water. It is used extensively for agricultural irrigation. The intermediate aquifer system consists of thin, discontinues lenses of sand, shell, and limestone between clays overlying the Floridan aquifer system. The intermediate aquifer system is an important part of the public water supply of the county because of the good quality of the water. The intermediate aquifer system has variable yields because of the discontinuous lenses. The surficial aquifer system is composed of sand and shell with varying fractions of finer materials. Well yields are small in the west and central parts of Flagler County, but the surficial aquifer system is an adequate source of domestic supply on the barrier island. A zone of freshwater in the surficial aquifer system is very important in the Hammock area, being the local source of most domestic supply in the area. Changes in hydrologic conditions from the 1950 's include a long-term decline in water levels in the Upper Floridan aquifer coincident with lower-than-average rainfall and a greater seasonal fluctuation of water levels. Chloride concentrations of water in the Upper Floridan aquifer do not appear to have changed significantly, presently ranging from 7 to 3,700 mg/L. Development will place stress on the aquifers and may result in upconing of brackish water in pumping centers and in lateral saltwater intrusion in coastal areas. (Author 's abstract)

Adjoint-Based Design of Rotors Using the Navier-Stokes Equations in a Noninertial Reference Frame

NASA Technical Reports Server (NTRS)

Nielsen, Eric J.; Lee-Rausch, Elizabeth M.; Jones, William T.

2010-01-01

Optimization of rotorcraft flowfields using an adjoint method generally requires a time-dependent implementation of the equations. The current study examines an intermediate approach in which a subset of rotor flowfields are cast as steady problems in a noninertial reference frame. This technique permits the use of an existing steady-state adjoint formulation with minor modifications to perform sensitivity analyses. The formulation is valid for isolated rigid rotors in hover or where the freestream velocity is aligned with the axis of rotation. Discrete consistency of the implementation is demonstrated by using comparisons with a complex-variable technique, and a number of single- and multipoint optimizations for the rotorcraft figure of merit function are shown for varying blade collective angles. Design trends are shown to remain consistent as the grid is refined.

Adjoint-Based Design of Rotors using the Navier-Stokes Equations in a Noninertial Reference Frame

NASA Technical Reports Server (NTRS)

Nielsen, Eric J.; Lee-Rausch, Elizabeth M.; Jones, William T.

2009-01-01

Optimization of rotorcraft flowfields using an adjoint method generally requires a time-dependent implementation of the equations. The current study examines an intermediate approach in which a subset of rotor flowfields are cast as steady problems in a noninertial reference frame. This technique permits the use of an existing steady-state adjoint formulation with minor modifications to perform sensitivity analyses. The formulation is valid for isolated rigid rotors in hover or where the freestream velocity is aligned with the axis of rotation. Discrete consistency of the implementation is demonstrated using comparisons with a complex-variable technique, and a number of single- and multi-point optimizations for the rotorcraft figure of merit function are shown for varying blade collective angles. Design trends are shown to remain consistent as the grid is refined.

Nestin-expressing cells in the pancreatic islets of Langerhans.

PubMed

Hunziker, E; Stein, M

2000-04-29

The pancreatic islets of Langerhans produce several peptide hormones, predominantly the metabolically active hormones insulin and glucagon, which are critical for maintaining normal fuel homeostasis. Some evidence exists that pancreatic endocrine cells turn over at a slow rate and can regenerate in certain conditions. This could be due to the presence of pluripotent cells residing in the pancreas. Recently the intermediate filament protein nestin has been identified to be a marker for a multipotent stem cell in the central nervous system. Given the similarity between the pancreatic islets and neuronal cells, we hypothesized that stem cells expressing nestin might be present in the pancreas. Here we present evidence that a subset of cells in the pancreatic islets express the stem cell marker nestin. These cells might serve as precursors of differentiated pancreatic endocrine cells. Copyright 2000 Academic Press.

A core phylogeny of Dictyostelia inferred from genomes representative of the eight major and minor taxonomic divisions of the group.

PubMed

Singh, Reema; Schilde, Christina; Schaap, Pauline

2016-11-17

Dictyostelia are a well-studied group of organisms with colonial multicellularity, which are members of the mostly unicellular Amoebozoa. A phylogeny based on SSU rDNA data subdivided all Dictyostelia into four major groups, but left the position of the root and of six group-intermediate taxa unresolved. Recent phylogenies inferred from 30 or 213 proteins from sequenced genomes, positioned the root between two branches, each containing two major groups, but lacked data to position the group-intermediate taxa. Since the positions of these early diverging taxa are crucial for understanding the evolution of phenotypic complexity in Dictyostelia, we sequenced six representative genomes of early diverging taxa. We retrieved orthologs of 47 housekeeping proteins with an average size of 890 amino acids from six newly sequenced and eight published genomes of Dictyostelia and unicellular Amoebozoa and inferred phylogenies from single and concatenated protein sequence alignments. Concatenated alignments of all 47 proteins, and four out of five subsets of nine concatenated proteins all produced the same consensus phylogeny with 100% statistical support. Trees inferred from just two out of the 47 proteins, individually reproduced the consensus phylogeny, highlighting that single gene phylogenies will rarely reflect correct species relationships. However, sets of two or three concatenated proteins again reproduced the consensus phylogeny, indicating that a small selection of genes suffices for low cost classification of as yet unincorporated or newly discovered dictyostelid and amoebozoan taxa by gene amplification. The multi-locus consensus phylogeny shows that groups 1 and 2 are sister clades in branch I, with the group-intermediate taxon D. polycarpum positioned as outgroup to group 2. Branch II consists of groups 3 and 4, with the group-intermediate taxon Polysphondylium violaceum positioned as sister to group 4, and the group-intermediate taxon Dictyostelium polycephalum branching at the base of that whole clade. Given the data, the approximately unbiased test rejects all alternative topologies favoured by SSU rDNA and individual proteins with high statistical support. The test also rejects monophyletic origins for the genera Acytostelium, Polysphondylium and Dictyostelium. The current position of Acytostelium ellipticum in the consensus phylogeny indicates that somatic cells were lost twice in Dictyostelia.

Interleukin-10 Is Produced by a Specific Subset of Taste Receptor Cells and Critical for Maintaining Structural Integrity of Mouse Taste Buds

PubMed Central

Chai, Jinghua; Zhou, Minliang; Simon, Nirvine; Huang, Liquan

2014-01-01

Although inflammatory responses are a critical component in defense against pathogens, too much inflammation is harmful. Mechanisms have evolved to regulate inflammation, including modulation by the anti-inflammatory cytokine interleukin-10 (IL-10). Previously we have shown that taste buds express various molecules involved in innate immune responses, including the proinflammatory cytokine tumor necrosis factor (TNF). Here, using a reporter mouse strain, we show that taste cells also express the anti-inflammatory cytokine IL-10. Remarkably, IL-10 is produced by only a specific subset of taste cells, which are different from the TNF-producing cells in mouse circumvallate and foliate taste buds: IL-10 expression was found exclusively in the G-protein gustducin-expressing bitter receptor cells, while TNF was found in sweet and umami receptor cells as reported previously. In contrast, IL-10R1, the ligand-binding subunit of the IL-10 receptor, is predominantly expressed by TNF-producing cells, suggesting a novel cellular hierarchy for regulating TNF production and effects in taste buds. In response to inflammatory challenges, taste cells can increase IL-10 expression both in vivo and in vitro. These findings suggest that taste buds use separate populations of taste receptor cells that coincide with sweet/umami and bitter taste reception to modulate local inflammatory responses, a phenomenon that has not been previously reported. Furthermore, IL-10 deficiency in mice leads to significant reductions in the number and size of taste buds, as well as in the number of taste receptor cells per taste bud, suggesting that IL-10 plays critical roles in maintaining structural integrity of the peripheral gustatory system. PMID:24523558

Early Short-Term Antiretroviral Therapy Is Associated with a Reduced Prevalence of CD8+FoxP3+ T Cells in Simian Immunodeficiency Virus-Infected Controller Rhesus Macaques

PubMed Central

George, Jeffy; Cofano, Egidio Brocca; Lybarger, Elizabeth; Louder, Mark; Lafont, Bernard A.P.; Mascola, John R.; Robert-Guroff, Marjorie

2011-01-01

Abstract Regulatory T cells contain a mix of CD4 and CD8 T cell subsets that can suppress immune activation and at the same time suppress immune responses, thereby contributing to disease progression. Recent studies have shown that an increased prevalence of CD8+FoxP3+ T regulatory cells was associated with immune suppression and diminished viral control in simian immunodeficiency virus (SIV)-infected rhesus macaques. Preventing an increase in the prevalence of CD8 T regulatory subsets is likely to lead to a better long-term outcome. Here we show that short-term antiretroviral therapy initiated within 1 week after SIV infection was associated with lower viral set point and immune activation after withdrawal of therapy as compared to untreated animals. Early short-term treated controller animals were found to have better SIV-specific immune responses and a significantly lower prevalence of immunosuppressive CD8+FoxP3+ T cells. Lower levels of CD8+FoxP3+ T cells coincided with preservation of CD4+FoxP3+ T cells at homeostatic levels, and significantly correlated with lower immune activation, suggesting a role for viral infection-driven immune activation in the expansion of CD8+FoxP3+ T cells. Interestingly, initiation of continuous therapy later in infection did not reduce the increased prevalence of CD8+FoxP3+ T cells to homeostatic levels. Taken together, our results suggest that early antiretroviral therapy preserves the integrity of the immune system leading to a lower viral set point in controller animals, and prevents alterations in the homeostatic balance between CD4+ and CD8+ T regulatory cells that could aid in better long-term outcome. PMID:21142402

Interleukin-10 is produced by a specific subset of taste receptor cells and critical for maintaining structural integrity of mouse taste buds.

PubMed

Feng, Pu; Chai, Jinghua; Zhou, Minliang; Simon, Nirvine; Huang, Liquan; Wang, Hong

2014-02-12

Although inflammatory responses are a critical component in defense against pathogens, too much inflammation is harmful. Mechanisms have evolved to regulate inflammation, including modulation by the anti-inflammatory cytokine interleukin-10 (IL-10). Previously we have shown that taste buds express various molecules involved in innate immune responses, including the proinflammatory cytokine tumor necrosis factor (TNF). Here, using a reporter mouse strain, we show that taste cells also express the anti-inflammatory cytokine IL-10. Remarkably, IL-10 is produced by only a specific subset of taste cells, which are different from the TNF-producing cells in mouse circumvallate and foliate taste buds: IL-10 expression was found exclusively in the G-protein gustducin-expressing bitter receptor cells, while TNF was found in sweet and umami receptor cells as reported previously. In contrast, IL-10R1, the ligand-binding subunit of the IL-10 receptor, is predominantly expressed by TNF-producing cells, suggesting a novel cellular hierarchy for regulating TNF production and effects in taste buds. In response to inflammatory challenges, taste cells can increase IL-10 expression both in vivo and in vitro. These findings suggest that taste buds use separate populations of taste receptor cells that coincide with sweet/umami and bitter taste reception to modulate local inflammatory responses, a phenomenon that has not been previously reported. Furthermore, IL-10 deficiency in mice leads to significant reductions in the number and size of taste buds, as well as in the number of taste receptor cells per taste bud, suggesting that IL-10 plays critical roles in maintaining structural integrity of the peripheral gustatory system.

Accumulation of M1-like macrophages in type 2 diabetic islets is followed by a systemic shift in macrophage polarization.

PubMed

Cucak, Helena; Grunnet, Lars Groth; Rosendahl, Alexander

2014-01-01

Human T2D is characterized by a low-grade systemic inflammation, loss of β-cells, and diminished insulin production. Local islet immunity is still poorly understood, and hence, we evaluated macrophage subpopulations in pancreatic islets in the well-established murine model of T2D, the db/db mouse. Already at 8 weeks of disease, on average, 12 macrophages were observed in the diabetic islets, whereas only two were recorded in the nondiabetic littermates. On a detailed level, the islet resident macrophages increased fourfold compared with nondiabetic littermates, whereas a pronounced recruitment (eightfold) of a novel subset of macrophages (CD68+F4/80-) was observed. The majority of the CD68+F4/80+ but only 40% of the CD68+F4/80- islet macrophages expressed CD11b. Both islet-derived macrophage subsets expressed moderate MHC-II, high galectin-3, and low CD80/CD86 levels, suggesting the cells to be macrophages rather than DCs. On a functional level, the vast majority of the macrophages in the diabetic islets was of the proinflammatory, M1-like phenotype. The systemic immunity in diabetic animals was characterized by a low-grade inflammation with elevated cytokine levels and increase of splenic cytokine, producing CD68+F4/80- macrophages. In late-stage diabetes, the cytokine signature changed toward a TGF-β-dominated profile, coinciding with a significant increase of galectin-3-positive macrophages in the spleen. In summary, our results show that proinflammatory M1-like galectin-3+ CD80/CD86(low) macrophages invade diabetic islets. Moreover, the innate immunity matures in a diabetes-dependent manner from an initial proinflammatory toward a profibrotic phenotype, supporting the concept that T2D is an inflammatory disease.

Improved classical and quantum random access codes

NASA Astrophysics Data System (ADS)

Liabøtrø, O.

2017-05-01

A (quantum) random access code ((Q)RAC) is a scheme that encodes n bits into m (qu)bits such that any of the n bits can be recovered with a worst case probability p >1/2 . We generalize (Q)RACs to a scheme encoding n d -levels into m (quantum) d -levels such that any d -level can be recovered with the probability for every wrong outcome value being less than 1/d . We construct explicit solutions for all n ≤d/2m-1 d -1 . For d =2 , the constructions coincide with those previously known. We show that the (Q)RACs are d -parity oblivious, generalizing ordinary parity obliviousness. We further investigate optimization of the success probabilities. For d =2 , we use the measure operators of the previously best-known solutions, but improve the encoding states to give a higher success probability. We conjecture that for maximal (n =4m-1 ,m ,p ) QRACs, p =1/2 {1 +[(√{3}+1)m-1 ] -1} is possible, and show that it is an upper bound for the measure operators that we use. We then compare (n ,m ,pq) QRACs with classical (n ,2 m ,pc) RACs. We can always find pq≥pc , but the classical code gives information about every input bit simultaneously, while the QRAC only gives information about a subset. For several different (n ,2 ,p ) QRACs, we see the same trade-off, as the best p values are obtained when the number of bits that can be obtained simultaneously is as small as possible. The trade-off is connected to parity obliviousness, since high certainty information about several bits can be used to calculate probabilities for parities of subsets.

African American men with low-grade prostate cancer have increased disease recurrence after prostatectomy compared with Caucasian men.

PubMed

Yamoah, Kosj; Deville, Curtiland; Vapiwala, Neha; Spangler, Elaine; Zeigler-Johnson, Charnita M; Malkowicz, Bruce; Lee, David I; Kattan, Michael; Dicker, Adam P; Rebbeck, Timothy R

2015-02-01

To explore whether disparities in outcomes exist between African American (AA) and Caucasian (CS) men with low-grade prostate cancer and similar cancer of the prostate risk assessment-postsurgery (CAPRA-S) features following prostatectomy (RP). The overall cohort consisted of 1,265 men (234 AA and 1,031 CS) who met the National comprehensive cancer network criteria for low- to intermediate-risk prostate cancer and underwent RP between 1990 and 2012. We first evaluated whether clinical factors were associated with adverse pathologic outcomes and freedom from biochemical failure (FFbF) using the entire cohort. Next, we studied a subset of 705 men (112 AA and 593 CS) who had pathologic Gleason score≤6 (low-grade disease). Using this cohort, we determined whether race affected FFbF in men with RP-proven low-grade disease and similar CAPRA-S scores. With a median follow-up time of 27 months, the overall 7-year FFbF rate was 86% vs. 79% in CS and AA men, respectively (P = 0.035). There was no significant difference in one or more adverse pathologic features between CS vs. AA men (27% vs. 31%; P = 0.35) or CAPRA-S score (P = 0.28). In the subset analysis of patients with low-grade disease, AA race was associated with worse FFbF outcomes (P = 0.002). Furthermore, AA race was a significant predictor of FFbF in men with low-grade disease (hazard ratio = 2.01, 95% CI: 1.08-3.72; P = 0.029). AA race is a predictor of worse FFbF outcomes in men with low-grade disease after RP. These results suggest that a subset of AA men with low-grade disease may benefit from more aggressive treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Predicting degree of benefit from adjuvant trastuzumab in NSABP trial B-31.

PubMed

Pogue-Geile, Katherine L; Kim, Chungyeul; Jeong, Jong-Hyeon; Tanaka, Noriko; Bandos, Hanna; Gavin, Patrick G; Fumagalli, Debora; Goldstein, Lynn C; Sneige, Nour; Burandt, Eike; Taniyama, Yusuke; Bohn, Olga L; Lee, Ahwon; Kim, Seung-Il; Reilly, Megan L; Remillard, Matthew Y; Blackmon, Nicole L; Kim, Seong-Rim; Horne, Zachary D; Rastogi, Priya; Fehrenbacher, Louis; Romond, Edward H; Swain, Sandra M; Mamounas, Eleftherios P; Wickerham, D Lawrence; Geyer, Charles E; Costantino, Joseph P; Wolmark, Norman; Paik, Soonmyung

2013-12-04

National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31 suggested the efficacy of adjuvant trastuzumab, even in HER2-negative breast cancer. This finding prompted us to develop a predictive model for degree of benefit from trastuzumab using archived tumor blocks from B-31. Case subjects with tumor blocks were randomly divided into discovery (n = 588) and confirmation cohorts (n = 991). A predictive model was built from the discovery cohort through gene expression profiling of 462 genes with nCounter assay. A predefined cut point for the predictive model was tested in the confirmation cohort. Gene-by-treatment interaction was tested with Cox models, and correlations between variables were assessed with Spearman correlation. Principal component analysis was performed on the final set of selected genes. All statistical tests were two-sided. Eight predictive genes associated with HER2 (ERBB2, c17orf37, GRB7) or ER (ESR1, NAT1, GATA3, CA12, IGF1R) were selected for model building. Three-dimensional subset treatment effect pattern plot using two principal components of these genes was used to identify a subset with no benefit from trastuzumab, characterized by intermediate-level ERBB2 and high-level ESR1 mRNA expression. In the confirmation set, the predefined cut points for this model classified patients into three subsets with differential benefit from trastuzumab with hazard ratios of 1.58 (95% confidence interval [CI] = 0.67 to 3.69; P = .29; n = 100), 0.60 (95% CI = 0.41 to 0.89; P = .01; n = 449), and 0.28 (95% CI = 0.20 to 0.41; P < .001; n = 442; P(interaction) between the model and trastuzumab < .001). We developed a gene expression-based predictive model for degree of benefit from trastuzumab and demonstrated that HER2-negative tumors belong to the moderate benefit group, thus providing justification for testing trastuzumab in HER2-negative patients (NSABP B-47).

Predicting Degree of Benefit From Adjuvant Trastuzumab in NSABP Trial B-31

PubMed Central

Pogue-Geile, Katherine L.; Kim, Chungyeul; Jeong, Jong-Hyeon; Tanaka, Noriko; Bandos, Hanna; Gavin, Patrick G.; Fumagalli, Debora; Goldstein, Lynn C.; Sneige, Nour; Burandt, Eike; Taniyama, Yusuke; Bohn, Olga L.; Lee, Ahwon; Kim, Seung-Il; Reilly, Megan L.; Remillard, Matthew Y.; Blackmon, Nicole L.; Kim, Seong-Rim; Horne, Zachary D.; Rastogi, Priya; Fehrenbacher, Louis; Romond, Edward H.; Swain, Sandra M.; Mamounas, Eleftherios P.; Wickerham, D. Lawrence; Geyer, Charles E.; Costantino, Joseph P.; Wolmark, Norman

2013-01-01

Background National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31 suggested the efficacy of adjuvant trastuzumab, even in HER2-negative breast cancer. This finding prompted us to develop a predictive model for degree of benefit from trastuzumab using archived tumor blocks from B-31. Methods Case subjects with tumor blocks were randomly divided into discovery (n = 588) and confirmation cohorts (n = 991). A predictive model was built from the discovery cohort through gene expression profiling of 462 genes with nCounter assay. A predefined cut point for the predictive model was tested in the confirmation cohort. Gene-by-treatment interaction was tested with Cox models, and correlations between variables were assessed with Spearman correlation. Principal component analysis was performed on the final set of selected genes. All statistical tests were two-sided. Results Eight predictive genes associated with HER2 (ERBB2, c17orf37, GRB7) or ER (ESR1, NAT1, GATA3, CA12, IGF1R) were selected for model building. Three-dimensional subset treatment effect pattern plot using two principal components of these genes was used to identify a subset with no benefit from trastuzumab, characterized by intermediate-level ERBB2 and high-level ESR1 mRNA expression. In the confirmation set, the predefined cut points for this model classified patients into three subsets with differential benefit from trastuzumab with hazard ratios of 1.58 (95% confidence interval [CI] = 0.67 to 3.69; P = .29; n = 100), 0.60 (95% CI = 0.41 to 0.89; P = .01; n = 449), and 0.28 (95% CI = 0.20 to 0.41; P < .001; n = 442; P interaction between the model and trastuzumab < .001). Conclusions We developed a gene expression–based predictive model for degree of benefit from trastuzumab and demonstrated that HER2-negative tumors belong to the moderate benefit group, thus providing justification for testing trastuzumab in HER2-negative patients (NSABP B-47). PMID:24262440

Altered expression of regulatory T and Th17 cells in murine bronchial asthma

PubMed Central

Zhu, Jianbo; Liu, Xiaoying; Wang, Wenxia; Ouyang, Xiuhe; Zheng, Wentao; Wang, Qingyuan

2017-01-01

Alteration of the careful balance of the ratio of Th1/Th2 cell subsets impacts immune function and plays an important role in the pathogenesis of asthma. There is little research on the impact of changes on the balance of the regulatory T (Treg)/Th17 subset ratio and its possible repercussions for asthma. This investigation used a murine model of asthma to measure the expression levels of Treg and Th17 cells and the levels of their transcription factors Foxp3 and retinoic acid receptor-related orphan nuclear receptor (ROR)γt in bronchial asthma while assessing indexes of airway inflammation. Thirty female SPF BALB/c mice were divided into three equally numbered groups: a normal control, an asthma and a dexamethasone treatment group. All the airway inflammation indexes measured were more prominent in the asthma group and less so in the control group. The percentage of the lymphocyte subset CD4+CD25+Foxp3+ cells in the CD4+ cells in the asthma group was significantly lower than that in the normal control group (P<0.01). The percentage of the lymphocyte subset CD4+IL-17+ cells in the CD4+ cells in the asthma group was significantly higher than that in the normal control group (P<0.01). The ratio of CD4+CD25+Foxp3+ cells/CD4+IL-17+ cells in the asthma group decreased compared with that in the normal control group (P<0.01). The expression level of Foxp3 of the mice in the asthma group was significantly lower than that in the control group (P<0.01). The expression intensity of RORγt in the asthma group was higher than that in the normal control group (P<0.01). Finally, the Foxp3/RORγt protein expression ratio in the asthma group was significantly lower than that in the normal control group (P<0.01). The Foxp3/RORγt protein expression ratio and the airway responsiveness were negatively correlated. The average levels of inflammation markers in the dexamethasone group were intermediate between the other groups. During the course of bronchial asthma the unbalanced expression of Treg and Th17 affects mostly the expression of Foxp3/RORγt, leading to inflammation of the airways. Dexamethasone may inhibit airway inflammation by regulating the balance between Treg and Th17. PMID:28672989

Refining multi-model projections of temperature extremes by evaluation against land-atmosphere coupling diagnostics

NASA Astrophysics Data System (ADS)

Sippel, Sebastian; Zscheischler, Jakob; Mahecha, Miguel D.; Orth, Rene; Reichstein, Markus; Vogel, Martha; Seneviratne, Sonia I.

2017-05-01

The Earth's land surface and the atmosphere are strongly interlinked through the exchange of energy and matter. This coupled behaviour causes various land-atmosphere feedbacks, and an insufficient understanding of these feedbacks contributes to uncertain global climate model projections. For example, a crucial role of the land surface in exacerbating summer heat waves in midlatitude regions has been identified empirically for high-impact heat waves, but individual climate models differ widely in their respective representation of land-atmosphere coupling. Here, we compile an ensemble of 54 combinations of observations-based temperature (T) and evapotranspiration (ET) benchmarking datasets and investigate coincidences of T anomalies with ET anomalies as a proxy for land-atmosphere interactions during periods of anomalously warm temperatures. First, we demonstrate that a large fraction of state-of-the-art climate models from the Coupled Model Intercomparison Project (CMIP5) archive produces systematically too frequent coincidences of high T anomalies with negative ET anomalies in midlatitude regions during the warm season and in several tropical regions year-round. These coincidences (high T, low ET) are closely related to the representation of temperature variability and extremes across the multi-model ensemble. Second, we derive a land-coupling constraint based on the spread of the T-ET datasets and consequently retain only a subset of CMIP5 models that produce a land-coupling behaviour that is compatible with these benchmark estimates. The constrained multi-model simulations exhibit more realistic temperature extremes of reduced magnitude in present climate in regions where models show substantial spread in T-ET coupling, i.e. biases in the model ensemble are consistently reduced. Also the multi-model simulations for the coming decades display decreased absolute temperature extremes in the constrained ensemble. On the other hand, the differences between projected and present-day climate extremes are affected to a lesser extent by the applied constraint, i.e. projected changes are reduced locally by around 0.5 to 1 °C - but this remains a local effect in regions that are highly sensitive to land-atmosphere coupling. In summary, our approach offers a physically consistent, diagnostic-based avenue to evaluate multi-model ensembles and subsequently reduce model biases in simulated and projected extreme temperatures.

A light- and calcium-gated transcription factor for imaging and manipulating activated neurons

PubMed Central

Wang, W.; Wildes, C. P.; Pattarabanjird, T.; Sanchez, M. I.; Glober, G.F.; Matthews, G. A.; Tye, K. M.; Ting, A. Y

2017-01-01

Activity remodels neurons, altering their molecular, structural, and electrical characteristics. To enable the selective characterization and manipulation of these neurons, we present FLARE, an engineered transcription factor that drives expression of fluorescent proteins, opsins, and other genetically-encoded tools only in the subset of neurons that experienced activity during a user-defined time window. FLARE senses the coincidence of elevated cytosolic calcium and externally-applied blue light, which together produce translocation of a membrane-anchored transcription factor to the nucleus to drive expression of any transgene. In cultured rat neurons, FLARE gives a light-to-dark signal ratio of 120 and a high-to-low calcium signal ratio of 10 after 10 minutes of stimulation. Channelrhodopsin expression permitted functional manipulation of FLARE-marked neurons. In adult mice, FLARE also gave light- and motor activity-dependent transcription in the cortex. Due to its modular design, minute-scale temporal resolution, and minimal dark-state leak, FLARE should be useful for the study of activity-dependent processes in neurons and other cells that signal with calcium. PMID:28650461

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

Bernal, José Luis; Cuesta, Antonio J.; Verde, Licia, E-mail: joseluis.bernal@icc.ub.edu, E-mail: liciaverde@icc.ub.edu, E-mail: ajcuesta@icc.ub.edu

We perform an empirical consistency test of General Relativity/dark energy by disentangling expansion history and growth of structure constraints. We replace each late-universe parameter that describes the behavior of dark energy with two meta-parameters: one describing geometrical information in cosmological probes, and the other controlling the growth of structure. If the underlying model (a standard wCDM cosmology with General Relativity) is correct, that is under the null hypothesis, the two meta-parameters coincide. If they do not, it could indicate a failure of the model or systematics in the data. We present a global analysis using state-of-the-art cosmological data sets whichmore » points in the direction that cosmic structures prefer a weaker growth than that inferred by background probes. This result could signify inconsistencies of the model, the necessity of extensions to it or the presence of systematic errors in the data. We examine all these possibilities. The fact that the result is mostly driven by a specific sub-set of galaxy clusters abundance data, points to the need of a better understanding of this probe.« less

ADP-ribosylation Factor 6 (ARF6) Bidirectionally Regulates Dendritic Spine Formation Depending on Neuronal Maturation and Activity*

PubMed Central

Kim, Yoonju; Lee, Sang-Eun; Park, Joohyun; Kim, Minhyung; Lee, Boyoon; Hwang, Daehee; Chang, Sunghoe

2015-01-01

Recent studies have reported conflicting results regarding the role of ARF6 in dendritic spine development, but no clear answer for the controversy has been suggested. We found that ADP-ribosylation factor 6 (ARF6) either positively or negatively regulates dendritic spine formation depending on neuronal maturation and activity. ARF6 activation increased the spine formation in developing neurons, whereas it decreased spine density in mature neurons. Genome-wide microarray analysis revealed that ARF6 activation in each stage leads to opposite patterns of expression of a subset of genes that are involved in neuronal morphology. ARF6-mediated Rac1 activation via the phospholipase D pathway is the coincident factor in both stages, but the antagonistic RhoA pathway becomes involved in the mature stage. Furthermore, blocking neuronal activity in developing neurons using tetrodotoxin or enhancing the activity in mature neurons using picrotoxin or chemical long term potentiation reversed the effect of ARF6 on each stage. Thus, activity-dependent dynamic changes in ARF6-mediated spine structures may play a role in structural plasticity of mature neurons. PMID:25605715

A light- and calcium-gated transcription factor for imaging and manipulating activated neurons.

PubMed

Wang, Wenjing; Wildes, Craig P; Pattarabanjird, Tanyaporn; Sanchez, Mateo I; Glober, Gordon F; Matthews, Gillian A; Tye, Kay M; Ting, Alice Y

2017-09-01

Activity remodels neurons, altering their molecular, structural, and electrical characteristics. To enable the selective characterization and manipulation of these neurons, we present FLARE, an engineered transcription factor that drives expression of fluorescent proteins, opsins, and other genetically encoded tools only in the subset of neurons that experienced activity during a user-defined time window. FLARE senses the coincidence of elevated cytosolic calcium and externally applied blue light, which together produce translocation of a membrane-anchored transcription factor to the nucleus to drive expression of any transgene. In cultured rat neurons, FLARE gives a light-to-dark signal ratio of 120 and a high- to low-calcium signal ratio of 10 after 10 min of stimulation. Opsin expression permitted functional manipulation of FLARE-marked neurons. In adult mice, FLARE also gave light- and motor-activity-dependent transcription in the cortex. Due to its modular design, minute-scale temporal resolution, and minimal dark-state leak, FLARE should be useful for the study of activity-dependent processes in neurons and other cells that signal with calcium.

Tips and tricks for flow cytometry-based analysis and counting of microparticles.

PubMed

Poncelet, Philippe; Robert, Stéphane; Bailly, Nicolas; Garnache-Ottou, Francine; Bouriche, Tarik; Devalet, Bérangère; Segatchian, Jerard H; Saas, Philippe; Mullier, François

2015-10-01

Submicron-sized extra-cellular vesicles generated by budding from the external cell membranes, microparticles (MPs) are important actors in transfusion as well as in other medical specialties. After briefly positioning their role in the characterization of labile blood products, this technically oriented chapter aims to review practical points that need to be considered when trying to use flow cytometry for the analysis, characterization and absolute counting of MP subsets. Subjects of active discussions relative to instrumentation will include the choice of the trigger parameter, possible standardization approaches requiring instrument quality-control, origin and control of non-specific background and of coincidence artifacts, choice of the type of electronic signals, optimal sheath fluid and sample speed. Questions related to reagents will cover target antigens and receptors, multi-color reagents, negative controls, enumeration of MPs and limiting artifacts due to unexpected (micro-) coagulation of plasma samples. Newly detected problems are generating innovative solutions and flow cytometry will continue to remain the technology of choice for the analysis of MPs, in the domain of transfusion as well as in many diverse specialties. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neonatal microbial colonization in mice promotes prolonged dominance of CD11b(+)Gr-1(+) cells and accelerated establishment of the CD4(+) T cell population in the spleen.

PubMed

Kristensen, Matilde B; Metzdorff, Stine B; Bergström, Anders; Damlund, Dina S M; Fink, Lisbeth N; Licht, Tine R; Frøkiær, Hanne

2015-09-01

To assess the microbial influence on postnatal hematopoiesis, we examined the role of early life microbial colonization on the composition of leukocyte subsets in the neonatal spleen. A high number of CD11b(+)Gr-1(+) splenocytes present perinatally was sustained for a longer period in conventionally colonized (CONV) mice than in mono-colonized (MC) and germfree (GF) mice, and the CD4(+) T cell population established faster in CONV mice. At the day of birth, compared to GF mice, the expression of Cxcl2 was up-regulated and Arg1 down-regulated in livers of CONV mice. This coincided with lower abundance of polylobed cells in the liver of CONV mice. An earlier peak in the expression of the genes Tjp1, Cdh1, and JamA in intestinal epithelial cells of CONV mice indicated an accelerated closure of the epithelial barrier. In conclusion, we have identified an important microbiota-dependent neonatal hematopoietic event, which we suggest impacts the subsequent development of the T cell population in the murine spleen.

FORTE Compact Intra-cloud Discharge Detection parameterized by Peak Current

NASA Astrophysics Data System (ADS)

Heavner, M. J.; Suszcynsky, D. M.; Jacobson, A. R.; Heavner, B. D.; Smith, D. A.

2002-12-01

The Los Alamos Sferic Array (EDOT) has recorded over 3.7 million lightning-related fast electric field change data records during April 1 - August 31, 2001 and 2002. The events were detected by three or more stations, allowing for differential-time-of-arrival location determination. The waveforms are characterized with estimated peak currents as well as by event type. Narrow Bipolar Events (NBEs), the VLF/LF signature of Compact Intra-cloud Discharges (CIDs), are generally isolated pulses with identifiable ionospheric reflections, permitting determination of event source altitudes. We briefly review the EDOT characterization of events. The FORTE satellite observes Trans-Ionospheric Pulse Pairs (TIPPs, the VHF satellite signature of CIDs). The subset of coincident EDOT and FORTE CID observations are compared with the total EDOT CID database to characterize the VHF detection efficiency of CIDs. The NBE polarity and altitude are also examined in the context of FORTE TIPP detection. The parameter-dependent detection efficiencies are extrapolated from FORTE orbit to GPS orbit in support of the V-GLASS effort (GPS based global detection of lightning).

Stealth configurations in vector-tensor theories of gravity

NASA Astrophysics Data System (ADS)

Chagoya, Javier; Tasinato, Gianmassimo

2018-01-01

Studying the physics of compact objects in modified theories of gravity is important for understanding how future observations can test alternatives to General Relativity. We consider a subset of vector-tensor Galileon theories of gravity characterized by new symmetries, which can prevent the propagation of the vector longitudinal polarization, even in absence of Abelian gauge invariance. We investigate new spherically symmetric and slowly rotating solutions for these systems, including an arbitrary matter Lagrangian. We show that, under certain conditions, there always exist stealth configurations whose geometry coincides with solutions of Einstein gravity coupled with the additional matter. Such solutions have a non-trivial profile for the vector field, characterized by independent integration constants, which extends to asymptotic infinity. We interpret our findings in terms of the symmetries and features of the original vector-tensor action, and on the number of degrees of freedom that it propagates. These results are important to eventually describe gravitationally bound configurations in modified theories of gravity, such as black holes and neutron stars, including realistic matter fields forming or surrounding the object.

Loss of Olfactory Receptor Genes Coincides with the Acquisition of Full Trichromatic Vision in Primates

PubMed Central

Wiebe, Victor; Przeworski, Molly; Lancet, Doron; Pääbo, Svante

2004-01-01

Olfactory receptor (OR) genes constitute the molecular basis for the sense of smell and are encoded by the largest gene family in mammalian genomes. Previous studies suggested that the proportion of pseudogenes in the OR gene family is significantly larger in humans than in other apes and significantly larger in apes than in the mouse. To investigate the process of degeneration of the olfactory repertoire in primates, we estimated the proportion of OR pseudogenes in 19 primate species by surveying randomly chosen subsets of 100 OR genes from each species. We find that apes, Old World monkeys and one New World monkey, the howler monkey, have a significantly higher proportion of OR pseudogenes than do other New World monkeys or the lemur (a prosimian). Strikingly, the howler monkey is also the only New World monkey to possess full trichromatic vision, along with Old World monkeys and apes. Our findings suggest that the deterioration of the olfactory repertoire occurred concomitant with the acquisition of full trichromatic color vision in primates. PMID:14737185

The noncoding RNA IPW regulates the imprinted DLK1-DIO3 locus in an induced pluripotent stem cell model of Prader-Willi syndrome.

PubMed

Stelzer, Yonatan; Sagi, Ido; Yanuka, Ofra; Eiges, Rachel; Benvenisty, Nissim

2014-06-01

Parental imprinting is a form of epigenetic regulation that results in parent-of-origin differential gene expression. To study Prader-Willi syndrome (PWS), a developmental imprinting disorder, we generated case-derived induced pluripotent stem cells (iPSCs) harboring distinct aberrations in the affected region on chromosome 15. In studying PWS-iPSCs and human parthenogenetic iPSCs, we unexpectedly found substantial upregulation of virtually all maternally expressed genes (MEGs) in the imprinted DLK1-DIO3 locus on chromosome 14. Subsequently, we determined that IPW, a long noncoding RNA in the critical region of the PWS locus, is a regulator of the DLK1-DIO3 region, as its overexpression in PWS and parthenogenetic iPSCs resulted in downregulation of MEGs in this locus. We further show that gene expression changes in the DLK1-DIO3 region coincide with chromatin modifications rather than DNA methylation levels. Our results suggest that a subset of PWS phenotypes may arise from dysregulation of an imprinted locus distinct from the PWS region.

Isolation of an Asymmetric RNA Uncoating Intermediate for a Single-Stranded RNA Plant Virus

PubMed Central

Bakker, Saskia E.; Ford, Robert J.; Barker, Amy M.; Robottom, Janice; Saunders, Keith; Pearson, Arwen R.; Ranson, Neil A.; Stockley, Peter G.

2012-01-01

We have determined the three-dimensional structures of both native and expanded forms of turnip crinkle virus (TCV), using cryo-electron microscopy, which allows direct visualization of the encapsidated single-stranded RNA and coat protein (CP) N-terminal regions not seen in the high-resolution X-ray structure of the virion. The expanded form, which is a putative disassembly intermediate during infection, arises from a separation of the capsid-forming domains of the CP subunits. Capsid expansion leads to the formation of pores that could allow exit of the viral RNA. A subset of the CP N-terminal regions becomes proteolytically accessible in the expanded form, although the RNA remains inaccessible to nuclease. Sedimentation velocity assays suggest that the expanded state is metastable and that expansion is not fully reversible. Proteolytically cleaved CP subunits dissociate from the capsid, presumably leading to increased electrostatic repulsion within the viral RNA. Consistent with this idea, electron microscopy images show that proteolysis introduces asymmetry into the TCV capsid and allows initial extrusion of the genome from a defined site. The apparent formation of polysomes in wheat germ extracts suggests that subsequent uncoating is linked to translation. The implication is that the viral RNA and its capsid play multiple roles during primary infections, consistent with ribosome-mediated genome uncoating to avoid host antiviral activity. PMID:22306464

The Number Density of Quiescent Compact Galaxies at Intermediate Redshift

NASA Astrophysics Data System (ADS)

Damjanov, Ivana; Hwang, Ho Seong; Geller, Margaret J.; Chilingarian, Igor

2014-09-01

Massive compact systems at 0.2 < z < 0.6 are the missing link between the predominantly compact population of massive quiescent galaxies at high redshift and their analogs and relics in the local volume. The evolution in number density of these extreme objects over cosmic time is the crucial constraining factor for the models of massive galaxy assembly. We select a large sample of ~200 intermediate-redshift massive compacts from the Baryon Oscillation Spectroscopic Survey (BOSS) spectroscopy by identifying point-like Sloan Digital Sky Survey photometric sources with spectroscopic signatures of evolved redshifted galaxies. A subset of our targets have publicly available high-resolution ground-based images that we use to augment the dynamical and stellar population properties of these systems by their structural parameters. We confirm that all BOSS compact candidates are as compact as their high-redshift massive counterparts and less than half the size of similarly massive systems at z ~ 0. We use the completeness-corrected numbers of BOSS compacts to compute lower limits on their number densities in narrow redshift bins spanning the range of our sample. The abundance of extremely dense quiescent galaxies at 0.2 < z < 0.6 is in excellent agreement with the number densities of these systems at high redshift. Our lower limits support the models of massive galaxy assembly through a series of minor mergers over the redshift range 0 < z < 2.

The role of the dynein light intermediate chain in retrograde IFT and flagellar function in Chlamydomonas

PubMed Central

Reck, Jaimee; Schauer, Alexandria M.; VanderWaal Mills, Kristyn; Bower, Raqual; Tritschler, Douglas; Perrone, Catherine A.; Porter, Mary E.

2016-01-01

The assembly of cilia and flagella depends on the activity of two microtubule motor complexes, kinesin-2 and dynein-2/1b, but the specific functions of the different subunits are poorly defined. Here we analyze Chlamydomonas strains expressing different amounts of the dynein 1b light intermediate chain (D1bLIC). Disruption of D1bLIC alters the stability of the dynein 1b complex and reduces both the frequency and velocity of retrograde intraflagellar transport (IFT), but it does not eliminate retrograde IFT. Flagellar assembly, motility, gliding, and mating are altered in a dose-dependent manner. iTRAQ-based proteomics identifies a small subset of proteins that are significantly reduced or elevated in d1blic flagella. Transformation with D1bLIC-GFP rescues the mutant phenotypes, and D1bLIC-GFP assembles into the dynein 1b complex at wild-type levels. D1bLIC-GFP is transported with anterograde IFT particles to the flagellar tip, dissociates into smaller particles, and begins processive retrograde IFT in <2 s. These studies demonstrate the role of D1bLIC in facilitating the recycling of IFT subunits and other proteins, identify new components potentially involved in the regulation of IFT, flagellar assembly, and flagellar signaling, and provide insight into the role of D1bLIC and retrograde IFT in other organisms. PMID:27251063

Inhibition of elastase-pulmonary emphysema in dominant-negative MafB transgenic mice.

PubMed

Aida, Yasuko; Shibata, Yoko; Abe, Shuichi; Inoue, Sumito; Kimura, Tomomi; Igarashi, Akira; Yamauchi, Keiko; Nunomiya, Keiko; Kishi, Hiroyuki; Nemoto, Takako; Sato, Masamichi; Sato-Nishiwaki, Michiko; Nakano, Hiroshi; Sato, Kento; Kubota, Isao

2014-01-01

Alveolar macrophages (AMs) play important roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously demonstrated upregulation of the transcription factor MafB in AMs of mice exposed to cigarette smoke. The aim of this study was to elucidate the roles of MafB in the development of pulmonary emphysema. Porcine pancreatic elastase was administered to wild-type (WT) and dominant-negative (DN)-MafB transgenic (Tg) mice in which MafB activity was suppressed only in macrophages. We measured the mean linear intercept and conducted cell differential analysis of bronchoalveolar lavage (BAL) cells, surface marker analysis using flow cytometry, and immunohistochemical staining using antibodies to matrix metalloproteinase (MMP)-9 and MMP-12. Airspace enlargement of the lungs was suppressed significantly in elastase-treated DN-MafB Tg mice compared with treated WT mice. AMs with projected pseudopods were decreased in DN-MafB Tg mice. The number of cells intermediately positive for F4/80 and weakly or intermediately positive for CD11b, which are considered cell subsets of matured AMs, decreased in the BAL of DN-MafB Tg mice. Furthermore, MMP-9 and -12 were significantly downregulated in BAL cells of DN-MafB Tg mice. Because MMPs exacerbate emphysema, MafB may be involved in pulmonary emphysema development through altered maturation of macrophages and MMP expression.

Exploring graphene superlattices: Magneto-optical properties

NASA Astrophysics Data System (ADS)

Duque, C. A.; Hernández-Bertrán, M. A.; Morales, A. L.; de Dios-Leyva, M.

2017-02-01

We present a detailed study of magnetic subbands, wave functions, and transition strengths for graphene superlattices (SLs) subject to a perpendicular magnetic field. It is shown that, for a weak magnetic field, the flat subbands of a SL exhibiting extra Dirac points are grouped into subsets, each of which consists of a singlet subband and a nearly degenerate doublet subband, and one nearly degenerate triplet subband. It was found that the wave functions corresponding to a singlet or to a doublet are always located around the image in real space of the central or extra Dirac points in k-space. The latter properties were explained by assuming that the electron motion is quasi-classical. Our study revealed that, for an intermediate field, the general characteristics of the wave functions are very similar to those of the pristine graphene, while for weak field, their behavior is drastically different. The latter is characterized by rapid oscillations which were understood using the solutions provided by the formalism of Luttinger-Kohn. The study on transition strengths allows us to obtain, for SLs with extra Dirac points in a weak magnetic field and different polarizations, the conditions under which transitions between multiplets are approximately allowed. It was shown that these conditions correspond to an unusual selection rule that is broken when the magnetic field intensity increases from weak to an intermediate value.

MicroRNA expression at diagnosis adds relevant prognostic information to molecular categorization in patients with intermediate-risk cytogenetic acute myeloid leukemia.

PubMed

Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Tejero, R; Díaz, T; Pratcorona, M; Tormo, M; Ribera, J M; Escoda, L; Duarte, R; Gallardo, D; Heras, I; Queipo de Llano, M P; Bargay, J; Monzo, M; Sierra, J; Navarro, A; Esteve, J

2014-04-01

Acute myeloid leukemia (AML) is a heterogeneous disease, and optimal treatment varies according to cytogenetic risk factors and molecular markers. Several studies have demonstrated the prognostic importance of microRNAs (miRNAs) in AML. Here we report a potential association between miRNA expression and clinical outcome in 238 intermediate-risk cytogenetic AML (IR-AML) patients from 16 institutions in the CETLAM cooperative group. We first profiled 670 miRNAs in a subset of 85 IR-AML patients from a single institution and identified 10 outcome-related miRNAs. We then validated these 10 miRNAs by individual assays in the total cohort and confirmed the prognostic impact of 4 miRNAs. High levels of miR-196b and miR-644 were independently associated with shorter overall survival, and low levels of miR-135a and miR-409-3p with a higher risk of relapse. Interestingly, miR-135a and miR-409-3p maintained their independent prognostic value within the unfavorable molecular subcategory (wild-type NPM1 and CEBPA and/or FLT3-ITD), and miR-644 retained its value within the favorable molecular subcategory. miR-409-3p, miR-135a, miR-196b and mir-644 arose as prognostic markers for IR-AML, both overall and within specific molecular subgroups.

Combination of Markov state models and kinetic networks for the analysis of molecular dynamics simulations of peptide folding.

PubMed

Radford, Isolde H; Fersht, Alan R; Settanni, Giovanni

2011-06-09

Atomistic molecular dynamics simulations of the TZ1 beta-hairpin peptide have been carried out using an implicit model for the solvent. The trajectories have been analyzed using a Markov state model defined on the projections along two significant observables and a kinetic network approach. The Markov state model allowed for an unbiased identification of the metastable states of the system, and provided the basis for commitment probability calculations performed on the kinetic network. The kinetic network analysis served to extract the main transition state for folding of the peptide and to validate the results from the Markov state analysis. The combination of the two techniques allowed for a consistent and concise characterization of the dynamics of the peptide. The slowest relaxation process identified is the exchange between variably folded and denatured species, and the second slowest process is the exchange between two different subsets of the denatured state which could not be otherwise identified by simple inspection of the projected trajectory. The third slowest process is the exchange between a fully native and a partially folded intermediate state characterized by a native turn with a proximal backbone H-bond, and frayed side-chain packing and termini. The transition state for the main folding reaction is similar to the intermediate state, although a more native like side-chain packing is observed.

Dickkopf 3 Promotes the Differentiation of a Rostrolateral Midbrain Dopaminergic Neuronal Subset In Vivo and from Pluripotent Stem Cells In Vitro in the Mouse.

PubMed

Fukusumi, Yoshiyasu; Meier, Florian; Götz, Sebastian; Matheus, Friederike; Irmler, Martin; Beckervordersandforth, Ruth; Faus-Kessler, Theresa; Minina, Eleonora; Rauser, Benedict; Zhang, Jingzhong; Arenas, Ernest; Andersson, Elisabet; Niehrs, Christof; Beckers, Johannes; Simeone, Antonio; Wurst, Wolfgang; Prakash, Nilima

2015-09-30

Wingless-related MMTV integration site 1 (WNT1)/β-catenin signaling plays a crucial role in the generation of mesodiencephalic dopaminergic (mdDA) neurons, including the substantia nigra pars compacta (SNc) subpopulation that preferentially degenerates in Parkinson's disease (PD). However, the precise functions of WNT1/β-catenin signaling in this context remain unknown. Stem cell-based regenerative (transplantation) therapies for PD have not been implemented widely in the clinical context, among other reasons because of the heterogeneity and incomplete differentiation of the transplanted cells. This might result in tumor formation and poor integration of the transplanted cells into the dopaminergic circuitry of the brain. Dickkopf 3 (DKK3) is a secreted glycoprotein implicated in the modulation of WNT/β-catenin signaling. Using mutant mice, primary ventral midbrain cells, and pluripotent stem cells, we show that DKK3 is necessary and sufficient for the correct differentiation of a rostrolateral mdDA neuron subset. Dkk3 transcription in the murine ventral midbrain coincides with the onset of mdDA neurogenesis and is required for the activation and/or maintenance of LMX1A (LIM homeobox transcription factor 1α) and PITX3 (paired-like homeodomain transcription factor 3) expression in the corresponding mdDA precursor subset, without affecting the proliferation or specification of their progenitors. Notably, the treatment of differentiating pluripotent stem cells with recombinant DKK3 and WNT1 proteins also increases the proportion of mdDA neurons with molecular SNc DA cell characteristics in these cultures. The specific effects of DKK3 on the differentiation of rostrolateral mdDA neurons in the murine ventral midbrain, together with its known prosurvival and anti-tumorigenic properties, make it a good candidate for the improvement of regenerative and neuroprotective strategies in the treatment of PD. Significance statement: We show here that Dickkopf 3 (DKK3), a secreted modulator of WNT (Wingless-related MMTV integration site)/β-catenin signaling, is both necessary and sufficient for the proper differentiation and survival of a rostrolateral (parabrachial pigmented nucleus and dorsomedial substantia nigra pars compacta) mesodiencephalic dopaminergic neuron subset, using Dkk3 mutant mice and murine primary ventral midbrain and pluripotent stem cells. The progressive loss of these dopamine-producing mesodiencephalic neurons is a hallmark of human Parkinson's disease, which can up to now not be halted by clinical treatments of this disease. Thus, the soluble DKK3 protein might be a promising new agent for the improvement of current protocols for the directed differentiation of pluripotent and multipotent stem cells into mesodiencephalic dopaminergic neurons and for the promotion of their survival in situ. Copyright © 2015 the authors 0270-6474/15/3513386-17$15.00/0.

Memory and long-range correlations in chess games

NASA Astrophysics Data System (ADS)

Schaigorodsky, Ana L.; Perotti, Juan I.; Billoni, Orlando V.

2014-01-01

In this paper we report the existence of long-range memory in the opening moves of a chronologically ordered set of chess games using an extensive chess database. We used two mapping rules to build discrete time series and analyzed them using two methods for detecting long-range correlations; rescaled range analysis and detrended fluctuation analysis. We found that long-range memory is related to the level of the players. When the database is filtered according to player levels we found differences in the persistence of the different subsets. For high level players, correlations are stronger at long time scales; whereas in intermediate and low level players they reach the maximum value at shorter time scales. This can be interpreted as a signature of the different strategies used by players with different levels of expertise. These results are robust against the assignation rules and the method employed in the analysis of the time series.

Color distributions in E-S0 galaxies. I. Frequency and importance of dust patterns for various brands of E classified galaxies

NASA Astrophysics Data System (ADS)

Michard, R.

1998-06-01

From the consideration of a sample of color distributions in 67 E classified objects of the Local Supercluster, it is found that local dust features are much more frequent and important in disky E's than boxy E's. The subclass of undeterminate objects, those which cannot be assigned to the diE or boE groups, is intermediate. Subsets of objects of common properties are considered from the point of view of local dust features occurrence: giant boxy E's; minor boxy E's with rotational support; compact dwarfs; SB0-like E's. It is noted that the detection of dust features is more than twice less frequent in Virgo cluster ellipticals than in the full sample, but the significance of this result is not clear. Based on observations collected at the Canada-France-Hawaii Telescope and at the Observatoire du Pic du Midi

The Broad Spectrum of Human Natural Killer Cell Diversity.

PubMed

Freud, Aharon G; Mundy-Bosse, Bethany L; Yu, Jianhua; Caligiuri, Michael A

2017-11-21

Natural killer (NK) cells provide protection against infectious pathogens and cancer. For decades it has been appreciated that two major NK cell subsets (CD56 bright and CD56 dim ) exist in humans and have distinct anatomical localization patterns, phenotypes, and functions in immunity. In light of this traditional NK cell dichotomy, it is now clear that the spectrum of human NK cell diversity is much broader than originally appreciated as a result of variegated surface receptor, intracellular signaling molecule, and transcription factor expression; tissue-specific imprinting; and foreign antigen exposure. The recent discoveries of tissue-resident NK cell developmental intermediates, non-NK innate lymphoid cells, and the capacity for NK cells to adapt and differentiate into long-lived memory cells has added further complexity to this field. Here we review our current understanding of the breadth and generation of human NK cell diversity. Copyright © 2017 Elsevier Inc. All rights reserved.

Timing and searching millisecond pulsars in globular clusters

NASA Astrophysics Data System (ADS)

D'Amico, Nichi; Possenti, Andrea; Manchester, Dick; Johnston, Simon; Kramer, Michael; Sarkissian, John; Lyne, Andrew; Burgay, Marta; Corongiu, Alessandro; Camilo, Fernando; Bailes, Matthew; van Straten, Willem

2010-04-01

Timing the dozen pulsars discovered in P303 is ensuring high quality results: (a) the peculiarities (in position or projected acceleration) of all the 5 millisecond pulsars in NGC6752 suggested the presence of non thermal dynamics in the core, perhaps due to black-holes of intermediate mass; (b) the eclipsing pulsar in NGC6397 is a stereotype for studying the late evolution of exotic binaries. We propose to continue our timing project focusing mostly on NGC6752 at 20cm (in order to measure additional parameters useful to constrain the existence of a black-hole) and NGC6397 at 10cm (for studying the eclipse region and the orbital secular evolution). We also request time for performing observations for a new deeper than ever search for millisecond pulsars in a subset of suitable clusters. This revamped search (as well as the requested timing observations) will exploit the new back-ends (APSR and DFB4) now available at Parkes.

Analysis of cystic fibrosis gener product (CFTR) function in patients with pancreas divisum and recurrent acute pancreatitis.

PubMed

Gelrud, Andres; Sheth, Sunil; Banerjee, Subhas; Weed, Deborah; Shea, Julie; Chuttani, Ram; Howell, Douglas A; Telford, Jennifer J; Carr-Locke, David L; Regan, Meredith M; Ellis, Lynda; Durie, Peter R; Freedman, Steven D

2004-08-01

The mechanism by which pancreas divisum may lead to recurrent episodes of acute pancreatitis in a subset of individuals is unknown. Abnormalities of the cystic fibrosis gene product (CFTR) have been implicated in the genesis of idiopathic chronic pancreatitis. The aim of this study was to determine if CFTR function is abnormal in patients with pancreas divisum and recurrent acute pancreatitis (PD/RAP). A total of 69 healthy control subjects, 12 patients with PD/RAP, 16 obligate heterozygotes with a single CFTR mutation, and 95 patients with cystic fibrosis were enrolled. CFTR function was analyzed by nasal transepithelial potential difference testing in vivo. The outcomes of the PD/RAP patients following endoscopic and surgical treatments were concomitantly analyzed. Direct measurement of CFTR function in nasal epithelium in response to isoproterenol demonstrated that the values for PD/RAP were intermediate between those observed for healthy controls and cystic fibrosis patients. The median value was 13 mV for PD/RAP subjects, which was statistically different from healthy controls (22 mV, p= 0.001) and cystic fibrosis pancreatic sufficient (-1 mV, p < 0.0001) and pancreatic insufficient (-3 mV, p < 0.0001) patients. These results suggest a link between CFTR dysfunction and recurrent acute pancreatitis in patients with pancreas divisum and may explain why a subset of patients with pancreas divisum develops recurrent acute pancreatitis. Copyright 2004 American College of Gastroenterology

Allelic imbalance on chromosome 17p13 in borderline (low malignant potential) epithelial ovarian tumors.

PubMed

Zanotti, K M; Hart, W R; Kennedy, A W; Belinson, J L; Casey, G

1999-07-01

Borderline epithelial ovarian tumors (BEOTs) possess clinical and pathologic features intermediate between cystadenomas and cystadenocarcinomas. Although the clinical and pathologic characteristics of BEOTs are well described, the molecular aspects are poorly understood. Three regions of loss of heterozygosity (often referred to as allelic imbalance [AI] when identified by polymerase chain reaction) on chromosome 17p13, one of which includes the p53 gene, have been implicated in the development of ovarian and breast cancers. To provide evidence that genes in these regions also may be involved in the development of BEOTs, we undertook a detailed analysis of AI at all three loci in BEOTs from 21 patients. Seventeen of the BEOTs were serous and four were mucinous. Five of 21 tumors (24%) had AI at one or more loci. Four tumors had AI using the D17S695 marker, two of which showed AI only at this locus. In addition, three tumors exhibited AI at the D17S654 locus, one of which showed AI only at this locus. These data suggest that there may be two tumor suppressor genes distal to p53 involved in the development of at least a subset of BEOTs. Peritoneal implants from a subset of serous BEOTs also were evaluated for AI and were found to be concordant with the primary tumor in all cases. Their genetic similarity is consistent with the implantation theory of peritoneal spread of serous BEOTs in these cases.

Regulation of RNA polymerase III transcription during transformation of human IMR90 fibroblasts with defined genetic elements.

PubMed

Durrieu-Gaillard, Stéphanie; Dumay-Odelot, Hélène; Boldina, Galina; Tourasse, Nicolas J; Allard, Delphine; André, Fabrice; Macari, Françoise; Choquet, Armelle; Lagarde, Pauline; Drutel, Guillaume; Leste-Lasserre, Thierry; Petitet, Marion; Lesluyes, Tom; Lartigue-Faustin, Lydia; Dupuy, Jean-William; Chibon, Frédéric; Roeder, Robert G; Joubert, Dominique; Vagner, Stéphan; Teichmann, Martin

2018-01-01

RNA polymerase (Pol) III transcribes small untranslated RNAs that are essential for cellular homeostasis and growth. Its activity is regulated by inactivation of tumor suppressor proteins and overexpression of the oncogene c-MYC, but the concerted action of these tumor-promoting factors on Pol III transcription has not yet been assessed. In order to comprehensively analyse the regulation of Pol III transcription during tumorigenesis we employ a model system that relies on the expression of five genetic elements to achieve cellular transformation. Expression of these elements in six distinct transformation intermediate cell lines leads to the inactivation of TP53, RB1, and protein phosphatase 2A, as well as the activation of RAS and the protection of telomeres by TERT, thereby conducting to full tumoral transformation of IMR90 fibroblasts. Transformation is accompanied by moderately enhanced levels of a subset of Pol III-transcribed RNAs (7SK; MRP; H1). In addition, mRNA and/or protein levels of several Pol III subunits and transcription factors are upregulated, including increased protein levels of TFIIIB and TFIIIC subunits, of SNAPC1 and of Pol III subunits. Strikingly, the expression of POLR3G and of SNAPC1 is strongly enhanced during transformation in this cellular transformation model. Collectively, our data indicate that increased expression of several components of the Pol III transcription system accompanied by a 2-fold increase in steady state levels of a subset of Pol III RNAs is sufficient for sustaining tumor formation.

Dynamics and stoichiometry of nutrients and phytoplankton in waters influenced by the oxygen minimum zone in the eastern tropical Pacific

NASA Astrophysics Data System (ADS)

Franz, Jasmin; Krahmann, Gerd; Lavik, Gaute; Grasse, Patricia; Dittmar, Thorsten; Riebesell, Ulf

2012-04-01

The tropical South East Pacific is characterized by strong coastal upwelling on the narrow continental shelf and an intense oxygen minimum zone (OMZ) in the intermediate water layer. These hydrographic properties are responsible for a permanent supply of intermediate water masses to the surface rich in nutrients and with a remarkably low inorganic N:P stoichiometry. To investigate the impact of OMZ-influenced upwelling waters on phytoplankton growth, elemental and taxonomical composition we measured hydrographic and biogeochemical parameters along an east-west transect at 10°S in the tropical South East Pacific, stretching from the upwelling region above the narrow continental shelf to the well-stratified oceanic section of the eastern boundary regime. New production in the area of coastal upwelling was driven by large-sized phytoplankton (e.g. diatoms) with generally low N:P ratios (<16:1). While nitrate and phosphate concentrations were at levels not limiting phytoplankton growth along the entire transect, silicate depletion prohibited diatom growth further off-shore. A deep chlorophyll a maximum consisting of pico-/nano- (Synechococcus, flagellates) and microphytoplankton occurred within a pronounced thermocline in subsurface waters above the shelf break and showed intermediate N:P ratios close to Redfield proportions. High PON:POP (>20:1) ratios were observed in the stratified open ocean section of the transect, coinciding with the abundance of two strains of the pico-cyanobacterium Prochlorococcus; a high-light adapted strain in the surface layer and a low-light adapted strain occurring along the oxic-anoxic transition zone below the thermocline. Excess phosphate present along the entire transect did not appear to stimulate growth of nitrogen-fixing phytoplankton, as pigment fingerprinting did not indicate the presence of diazotrophic cyanobacteria at any of our sampling stations. Instead, a large fraction of the excess phosphate generated within the oxygen minimum zone was consumed by non-Redfield production of large phytoplankton in shelf surface waters.

Patterns of parasite transmission in polar seas: Daily rhythms of cercarial emergence from intertidal snails

NASA Astrophysics Data System (ADS)

Prokofiev, Vladimir V.; Galaktionov, Kirill V.; Levakin, Ivan A.

2016-07-01

Trematodes are common parasites in intertidal ecosystems. Cercariae, their dispersive larvae, ensure transmission of infection from the first intermediate molluscan host to the second intermediate (invertebrates and fishes) or the final (fishes, marine birds and mammals) host. Trematode transmission in polar seas, while interesting in many respects, is poorly studied. This study aimed to elucidate the patterns of cercarial emergence from intertidal snails at the White Sea and Barents Sea. The study, involving cercariae of 12 species, has provided the most extensive material obtained so far in high latitude seas (66-69° N). The experiments were conducted in situ. Multichannel singular spectral analysis (MSSA) used for processing primary data made it possible to estimate the relative contribution of different oscillations into the analysed time series and to separate the daily component from the other oscillatory components and the noise. Cercarial emergence had pronounced daily rhythms, which did not depend on the daily tidal schedule but were regulated by thermo- and photoperiod. Daily emergence maximums coincided with periods favourable for infecting the second intermediate hosts. Cercarial daily emergence rhythms differed in species using the same molluscan hosts which can be explained by cercarial host searching behaviour. Daily cercarial output (DCO) correlated negatively with larval volume and positively with that of the molluscan host except in cercariae using ambuscade behaviour. In the Barents Sea cercariae emerged from their molluscan hosts at lower temperatures than in the warmer White Sea but the daily emergence period was prolonged. Thus, DCO of related species were similar in these two seas and comparable with DCO values reported for boreal seas. Local temperature adaptations in cercarial emergence suggests that in case of Arctic climate warming trematode transmission in coastal ecosystems is likely to be intensified not because of the increased summer temperature but because of the prolongation of the warm season favouring cercarial emergence (transmission window).

Water mass modification at the Agulhas retroflection: chlorofluoromethane studies

NASA Astrophysics Data System (ADS)

Fine, Rana A.; Warner, Mark J.; Weiss, Ray F.

1988-03-01

Chlorofluoromethane (CFM) and hydrographic data from the 1983 Agulhas Retroflection cruise are used to show the importance of the region in ventilating thermocline and Intermediate Waters of the southwest Indian ocean gyre. Generally South Atlantic waters are more recently ventilated by at least two years than those of the South Indian Ocean, probably because the latter are farther downstream from the source regions near the South Atlantic subantarctic sector. A two-component mixing model shows that the outflow from the Agulhas Retroflection (14-4°C) was composed of South Indian water and at least 23% South Atlantic water. However, at the density of Indian sector Subantarctic Mode Water the inflow into the Agulhas Retroflection was well preserved in the outflow, and the South Atlantic and Indian waters appear to be ventilated by different water masses. In addition, strong interleaving was found throughout the survey area (between 14 and 4°C), characterized by correlations of negative salinity anomalies with high CFM concentrations. At the density of Antarctic Intermediate Water (AAIW) there was interleaving of both low salinity water and higher salinity Red Sea Water. Using estimates of past atmospheric ratios of two CFMs, we calculate that AAIW within the retroflection was 50-75% diluted by mixing with CFM-free water since leaving the source region. Results from the two-component mixing model, which show substantial contributions of South Atlantic water in the outflow, suggest that the return flow for the 10 Sv leakage of Indian Ocean water via the Agulhas Current into the South Atlantic [ GORDON (1985) Science, 227, 1030-1033; GORDONet al. (1987) Deep-Sea Research, 34, 565-600] is occurring at thermocline and intermediate depths. A combination of active mixing in this region and similarity in the ventilation processes may be the reason that the South Atlantic and Indian thermoclines are coincident in temperature and salinity space (between 15 and 7°C) as noted by Gordon.

Insights Into Intermediate Ocean Barium Cycling From Deep-Sea Bamboo Coral Records on the California Margin

NASA Astrophysics Data System (ADS)

LaVigne, M.; Serrato Marks, G.; Freiberger, M. M.; Miller, H. R.; Hill, T. M.; McNichol, A. P.; Lardie Gaylord, M.

2016-02-01

Dissolved barium (BaSW) has been linked to several biogeochemical processes such as the cycling and export of nutrients, organic carbon (Corg), and barite in surface and intermediate oceans. The dynamic nature of barium cycling in the water column has been demonstrated on short timescales (days-weeks) while sedimentary records have documented geologic-scale changes in barite preservation driven by export production. Our understanding of how inter-annual-decadal scale climate variability impacts these biogeochemical processes currently lacks robust instrumental and paleoceanographic records. Recent work has calibrated and demonstrated the reproducibility of a new BaSW proxy in California Current System (CCS) bamboo corals (Ba/Ca) using a coral depth transect spanning the CCS oxygen minimum zone (792-2055m water depth). New `reconnaissance' radiocarbon data identifying the bomb 14C spike in coral proteinaceous nodes and sclerochronological analyses of calcitic internodes are used to assign chronologies to the CCS coral records. Century-long coral records from 900-1500m record 4-7 year long increases in Ba/Ca ( 10-70 nmol/kg BaSW) at depths where rapid barite cycling occurs on day-weekly timescales. The BaSW peaks punctuate the coral records at different time periods and depths and do not coincide with inter-annual/decadal climate transitions (e.g. ENSO/PDO). Stable surface productivity and coral δ15N records indicate that Corg export from CCS surface waters has been relatively constant over the past century. Thus, the inter-annual scale BaSW peaks recorded by the 900-1500m corals more likely reflect periods of decreased barite formation (and/or increased dissolution) via reduced bacterial Corg respiration or barite saturation state. Paleoceanographic BaSW records and continued research on barium cycling in the modern ocean have the potential to elucidate the mechanisms linking intermediate water carbon and barium cycling, climate, and ocean oxygenation in the past.

Orbital effects in cobaltites by neutron scattering

NASA Astrophysics Data System (ADS)

Louca, Despina

2005-03-01

The orbital degree of freedom can play a central role in the physics of transition metal perovskite oxides because of its intricate coupling with other degrees of freedom such as spin, charge and lattice. In this talk the case of La1-xSrxCoO3 will be presented. Using elastic and inelastic neutron scattering, we investigated the thermal evolution of the local atomic structure and lattice dynamics in the pure sample and with the addition of charge carriers as the system crosses over from a paramagnetic insulator to a ferromagnetic metal. In LaCoO3, the thermal activation of the Co ions from a nonmagnetic ground state to an intermediate spin state gives rise to orbital degeneracy. This leads to Jahn-Teller distortions that are dynamical in nature. Doping stabilizes the intermediate spin configuration of the Co ions in the paramagnetic insulating phase. Evidence for local static Jahn-Teller distortions is observed but without long-range ordering. The size of the JT lattice is proportional to the amount of charge. However, with cooling to the metallic phase, static JT distortions disappear for x <= 30 %, the percolation limit. This coincides with narrowing of two modes at φ=22,nd,4,eV in the phonon spectrum in which we argue is due to localized dynamical JT fluctuations^1. The implications of the orbital effects to the structural and magnetic properties will be discussed. ^1D. Louca and J. L. Sarrao, Phys. Rev. Lett. 91, 155501 (2003).

Detection of two intervening Ne viii absorbers probing warm gas at z ˜ 0.6

NASA Astrophysics Data System (ADS)

Pachat, Sachin; Narayanan, Anand; Khaire, Vikram; Savage, Blair D.; Muzahid, Sowgat; Wakker, Bart P.

2017-10-01

We report on the detection of two Ne viii absorbers, at z = 0.619 07 and 0.570 52 in the Hubble Space Telescope/Cosmic Origins Spectrograph spectrum of background quasars SDSS J080908.13 + 461925.6 and SBS 1122 + 594, respectively. The Ne viii 770 line is at ˜3σ significance. In both instances, the Ne viii is found to be tracing gas with T ≳ 105 K, predominantly collisionally ionized, with moderate densities of n_{H} ≲ 10^{-4} cm-3, sub-solar metallicities and total hydrogen column densities of N(H) ≳ 1019 cm-2. In the z = 0.619 07 absorber, the low, intermediate ions and O VI are consistent with origin in photoionized gas, with the O VI potentially having some contribution from the warm collisional phase traced by Ne viii. The z = 0.570 52 system has H I absorption in at least three kinematically distinct components, with one of them having b({H I}) = 49 {± } 11 km s-1. The intermediate-ionization lines, O VI and Ne viii, are coincident in velocity with this component. Their different line widths suggest warm temperatures of T = (0.5-1.5) × 105 K. Both absorbers are residing in regions where there are several luminous (≳L★) galaxies. The absorber at z = 0.570 52 is within the virial radius of a 2.6L★ galaxy, possibly associated with shock-heated circumgalactic material.

Opposite behavior of two isozymes when refolding in the presence of non-ionic detergents.

PubMed Central

Doñate, F.; Artigues, A.; Iriarte, A.; Martinez-Carrion, M.

1998-01-01

GroEL has a greater affinity for the mitochondrial isozyme (mAAT) of aspartate aminotransferase than for its cytosolic counterpart (cAAT) (Mattingly JR Jr, Iriarte A, Martinez-Carrion M, 1995, J Biol Chem 270:1138-1148), two proteins that share a high degree of sequence similarity and an almost identical spatial structure. The effect of detergents on the refolding of these large, dimeric isozymes parallels this difference in behavior. The presence of non-ionic detergents such as Triton X-100 or lubrol at concentrations above their critical micelle concentration (CMC) interferes with reactivation of mAAT unfolded in guanidinium chloride but increases the yield of cAAT refolding at low temperatures. The inhibitory effect of detergents on the reactivation of mAAT decreases progressively as the addition of detergents is delayed after starting the refolding reaction. The rate of disappearance of the species with affinity for binding detergents coincides with the slowest of the two rate-limiting steps detected in the refolding pathway of mAAT. Limited proteolysis studies indicate that the overall structure of the detergent-bound mAAT resembles that of the protein in a complex with GroEL. The mAAT folding intermediates trapped in the presence of detergents can resume reactivation either upon dilution of the detergent below its CMC or by adding beta-cyclodextrin. Thus, isolation of otherwise transient productive folding intermediates for further characterization is possible through the use of detergents. PMID:10082379

Opposite behavior of two isozymes when refolding in the presence of non-ionic detergents.

PubMed

Doñate, F; Artigues, A; Iriarte, A; Martinez-Carrion, M

1998-08-01

GroEL has a greater affinity for the mitochondrial isozyme (mAAT) of aspartate aminotransferase than for its cytosolic counterpart (cAAT) (Mattingly JR Jr, Iriarte A, Martinez-Carrion M, 1995, J Biol Chem 270:1138-1148), two proteins that share a high degree of sequence similarity and an almost identical spatial structure. The effect of detergents on the refolding of these large, dimeric isozymes parallels this difference in behavior. The presence of non-ionic detergents such as Triton X-100 or lubrol at concentrations above their critical micelle concentration (CMC) interferes with reactivation of mAAT unfolded in guanidinium chloride but increases the yield of cAAT refolding at low temperatures. The inhibitory effect of detergents on the reactivation of mAAT decreases progressively as the addition of detergents is delayed after starting the refolding reaction. The rate of disappearance of the species with affinity for binding detergents coincides with the slowest of the two rate-limiting steps detected in the refolding pathway of mAAT. Limited proteolysis studies indicate that the overall structure of the detergent-bound mAAT resembles that of the protein in a complex with GroEL. The mAAT folding intermediates trapped in the presence of detergents can resume reactivation either upon dilution of the detergent below its CMC or by adding beta-cyclodextrin. Thus, isolation of otherwise transient productive folding intermediates for further characterization is possible through the use of detergents.

Protein Kinase G facilitates EGFR-mediated cell death in MDA-MB-468 cells

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

Jackson, Nicole M.; Ceresa, Brian P., E-mail: brian.ceresa@louisville.edu

The Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor tyrosine kinase with critical implications in cell proliferation, migration, wound healing and the regulation of apoptosis. However, the EGFR has been shown to be hyper-expressed in a number of human malignancies. The MDA-MB-468 metastatic breast cell line is one example of this. This particular cell line hyper-expresses the EGFR and undergoes EGFR-mediated apoptosis in response to EGF ligand. The goal of this study was to identify the kinases that could be potential intermediates for the EGFR-mediated induction of apoptosis intracellularly. After identifying Cyclic GMP-dependent Protein Kinase G (PKG) as amore » plausible intermediate, we wanted to determine the temporal relationship of these two proteins in the induction of apoptosis. We observed a dose-dependent decrease in MDA-MB-468 cell viability, which was co-incident with increased PKG activity as measured by VASPSer239 phosphorylation. In addition, we observed a dose dependent decrease in cell viability, as well as an increase in apoptosis, in response to two different PKG agonists, 8-Bromo-cGMP and 8-pCPT-cGMP. MDA-MB-468 cells with reduced PKG activity had attenuated EGFR-mediated apoptosis. These findings indicate that PKG does not induce cell death via transphosphorylation of the EGFR. Instead, PKG activity occurs following EGFR activation. Together, these data indicate PKG as an intermediary in EGFR-mediated cell death, likely via apoptotic pathway.« less

E 2 / M 1 Mixing Ratios in Transitions From the Gamma-Vibrational-Bands to the Ground-State-Rotational-Bands of 102 , 104 , 106 , 108Mo, 108 , 110 , 112Ru, and 112 , 114 , 116Pd

NASA Astrophysics Data System (ADS)

Eldridge, Jonathan M.; Fenker, B.; Goodin, C.; Hamilton, J. H.; Wang, E. H.; Ramayya, A. V.; Daniel, A. V.; Ter-Akopian, G. M.; Luo, Y. X.; Rasmussen, J. O.; Oganesson, Yu. Ts.; Zhu, S. J.

2017-09-01

E 2 / M 1 mixing ratios have been measured for transitions from states in the γ-vibrational-bands (Iγ+) to states in the ground-state-bands (Ig+ or [I- 1 ] g +) of the neutron rich, deformed isotopes, 102 , 104 , 106 , 108Mo, 108 , 110 , 112Ru, and 112 , 114 , 116Pd, including from states as high as 9γ+. These measurements were done using the GAMMASPHERE detector array, which, at the time of the experiment, had 101 working HPGe detectors, arranged at 64 different angles. A 62 μCi source of 252Cf was placed inside GAMMASPHERE yielding 5.7 ×1011 γ - γ - γ and higher coincidence events. The angular correlation between the transitions from the γ-band to the ground band, and the pure E2 transitions within the ground band were then measured. These angular correlations yielded the mixing ratios, demonstrating that these transitions are all pure or nearly pure E2, in agreement with theory. In order to correct for possible attenuation due to the lifetime of the intermediate state in these correlations, the g-factors of the intermediate states needed to be known. Therefore, the g-factors of the 2g+ states in the ground state band have been measured. Supported by the US Department of Energy; Grant No. DE-FG0588ER40407, Contract No. DE-AC03-76SF00098.

Crustal structure across the Three Gorges area of the Yangtze platform, central China, from seismic refraction/wide-angle reflection data

USGS Publications Warehouse

Zhang, Z.; Bai, Z.; Mooney, W.; Wang, C.; Chen, X.; Wang, E.; Teng, J.; Okaya, N.

2009-01-01

We present active-source seismic data recorded along a 300??km-long profile across the Three Gorges area of the western Yangtze platform, central China. From west to east, the profile crosses the Zigui basin, Huangling dome and Jianghan basin. The derived crustal P-wave velocity structure changes significantly across the Tongchenghe fault that lies at the transition from the Huangling dome to the Jianghan basin. West of the Tongchenghe fault, beneath the Zigui basin and the Huangling dome, we observe a ~ 42??km thick crust of relatively low average velocity (6.3-6.4??km/s). In contrast, east of the Tongchenghe fault, beneath the Jianghan basin, the crust is only 30??km thick and has a high average velocity (6.6-6.7??km/s). A west-east variation in crustal composition along the Tongchenghe fault is also inferred. West of the fault, P-wave velocities suggest a felsic composition with an intermediate layer at the base of the crust, whilst, east of the fault, felsic, intermediate, and mafic crustal layers are apparent. Our results suggest that the crust beneath the Jianghan basin has been thinned by rifting, accompanied by intrusion of the lower crust by mafic dikes and sills. The west-to-east division of the crust in the Three Gorges area coincides with first-order geophysical contrasts in gravity, topography, crustal and lithospheric thickness. ?? 2009 Elsevier B.V.

The merger remnant NGC 3610 and its globular cluster system: a large-scale study

NASA Astrophysics Data System (ADS)

Bassino, Lilia P.; Caso, Juan P.

2017-04-01

We present a photometric study of the prototype merger remnant NGC 3610 and its globular cluster (GC) system, based on new Gemini/GMOS and Advanced Camera for Surveys/Hubble Space Telescope archival images. Thanks to the large field of view of our GMOS data, larger than previous studies, we are able to detect a 'classical' bimodal GC colour distribution, corresponding to metal-poor and metal-rich GCs, at intermediate radii and a small subsample of likely young clusters of intermediate colours, mainly located in the outskirts. The extent of the whole GC system is settled as about 40 kpc. The GC population is quite poor, about 500 ± 110 members that corresponds to a low total specific frequency SN ˜ 0.8. The effective radii of a cluster sample are determined, including those of two spectroscopically confirmed young and metal-rich clusters, that are in the limit between GC and UCD sizes and brightness. The large-scale galaxy surface-brightness profile can be decomposed as an inner embedded disc and an outer spheroid, determining for both larger extents than earlier research (10 and 30 kpc, respectively). We detect boxy isophotes, expected in merger remnants, and show a wealth of fine-structure in the surface-brightness distribution with unprecedented detail, coincident with the outer spheroid. The lack of symmetry in the galaxy colour map adds a new piece of evidence to the recent merger scenario of NGC 3610.

Design of a multi-center immunophenotyping analysis of peripheral blood, sputum and bronchoalveolar lavage fluid in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS).

PubMed

Freeman, Christine M; Crudgington, Sean; Stolberg, Valerie R; Brown, Jeanette P; Sonstein, Joanne; Alexis, Neil E; Doerschuk, Claire M; Basta, Patricia V; Carretta, Elizabeth E; Couper, David J; Hastie, Annette T; Kaner, Robert J; O'Neal, Wanda K; Paine, Robert; Rennard, Stephen I; Shimbo, Daichi; Woodruff, Prescott G; Zeidler, Michelle; Curtis, Jeffrey L

2015-01-27

Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) is a multi-center longitudinal, observational study to identify novel phenotypes and biomarkers of chronic obstructive pulmonary disease (COPD). In a subset of 300 subjects enrolled at six clinical centers, we are performing flow cytometric analyses of leukocytes from induced sputum, bronchoalveolar lavage (BAL) and peripheral blood. To minimize several sources of variability, we use a "just-in-time" design that permits immediate staining without pre-fixation of samples, followed by centralized analysis on a single instrument. The Immunophenotyping Core prepares 12-color antibody panels, which are shipped to the six Clinical Centers shortly before study visits. Sputum induction occurs at least two weeks before a bronchoscopy visit, at which time peripheral blood and bronchoalveolar lavage are collected. Immunostaining is performed at each clinical site on the day that the samples are collected. Samples are fixed and express shipped to the Immunophenotyping Core for data acquisition on a single modified LSR II flow cytometer. Results are analyzed using FACS Diva and FloJo software and cross-checked by Core scientists who are blinded to subject data. Thus far, a total of 152 sputum samples and 117 samples of blood and BAL have been returned to the Immunophenotyping Core. Initial quality checks indicate useable data from 126 sputum samples (83%), 106 blood samples (91%) and 91 BAL samples (78%). In all three sample types, we are able to identify and characterize the activation state or subset of multiple leukocyte cell populations (including CD4+ and CD8+ T cells, B cells, monocytes, macrophages, neutrophils and eosinophils), thereby demonstrating the validity of the antibody panel. Our study design, which relies on bi-directional communication between clinical centers and the Core according to a pre-specified protocol, appears to reduce several sources of variability often seen in flow cytometric studies involving multiple clinical sites. Because leukocytes contribute to lung pathology in COPD, these analyses will help achieve SPIROMICS aims of identifying subgroups of patients with specific COPD phenotypes. Future analyses will correlate cell-surface markers on a given cell type with smoking history, spirometry, airway measurements, and other parameters. This study was registered with ClinicalTrials.gov as NCT01969344 .

Characterization of kidney CD45intCD11bintF4/80+MHCII+CX3CR1+Ly6C- "intermediate mononuclear phagocytic cells".

PubMed

Lee, Sul A; Noel, Sanjeev; Sadasivam, Mohanraj; Allaf, Mohamad E; Pierorazio, Phillip M; Hamad, Abdel R A; Rabb, Hamid

2018-01-01

Kidney immune cells play important roles in pathogenesis of many diseases, including ischemia-reperfusion injury (IRI) and transplant rejection. While studying murine kidney T cells, we serendipitously identified a kidney mononuclear phagocytic cell (MPC) subset characterized by intermediate surface expression of CD45 and CD11b. These CD45intCD11bint MPCs were further identified as F4/80+MHCII+CX3CR1+Ly6C- cells, comprising ~17% of total CD45+ cells in normal mouse kidney (P < 0.01) and virtually absent from all other organs examined except the heart. Systemic clodronate treatment had more significant depletive effect on the CD45intCD11bint population (77.3%±5.9%, P = 0.03) than on CD45highCD11b+ population (14.8%±16.6%, P = 0.49). In addition, CD45intCD11bint MPCs had higher phagocytic function in the normal kidney (35.6%±3.3% vs. 24.1%±2.2%, P = 0.04), but lower phagocytic capacity in post-ischemic kidney (54.9%±1.0% vs. 67.8%±1.9%, P < 0.01) compared to the CD45highCD11b+ population. Moreover, the CD45intCD11bint population had higher intracellular production of the pro-inflammatory tumor necrosis factor (TNF)-α (58.4%±5.2% vs. 27.3%±0.9%, P < 0.001) after lipopolysaccharide (LPS) stimulation and lower production of the anti-inflammatory interleukin (IL)-10 (7.2%±1.3% vs. 14.9%±2.2%, P = 0.02) following kidney IRI, suggesting a functional role under inflammatory conditions. The CD45intCD11bint cells increased early after IRI, and then abruptly decreased 48h later, whereas CD45highCD11b+ cells steadily increased after IRI before declining at 72h (P = 0.03). We also identified the CD45intCD11bint MPC subtype in human kidney. We conclude that CD45intCD11bint F4/80+MHCII+CX3CR1+Ly6C-population represent a unique subset of MPCs found in both mouse and human kidneys. Future studies will further characterize their role in kidney health and disease.

Diagenesis of Upper Carboniferous rocks in the Ouachita foreland shelf in mid-continent USA: an overview of widespread effects of a Variscan-equivalent orogeny

USGS Publications Warehouse

Walton, A.W.; Wojcik, K.M.; Goldstein, R.H.; Barker, C.E.

1995-01-01

Diagenesis of Upper Carboniferous foreland shelf rocks in southeastern Kansas took place at temperatures as high as 100-150?? C at a depth of less than 2 km. High temperatures are the result of the long distance (hundreds of kilometers) advection of groundwater related to collisional orogeny in the Ouachita tectonic belt to the south. Orogenic activity in the Ouachita area was broadly Late Carboniferous, equivalent to the Variscan activity of Europe. Mississippi Valley-type Pb-Zn deposits and oil and gas fields in the US midcontinent and elsewhere are commonly attributed to regional groundwater flow resulting from such collisional events. This paper describes the diagenesis and thermal effects in sandstone and limestone of Upper Carboniferous siliciclastic and limestone-shale cyclothems, the purported confining layer of a supposed regional aquifer. Diagenesis took place in early, intermediate, and late stages. Many intermediate and late stage events in the sandstones have equivalents in the limestones, suggesting that the causes were regional. The sandstone paragenesis includes siderite cement (early stage), quartz overgrowths (intermediate stage), dissolution of feldspar and carbonates, followed by minor Fe calcite, pore-filling kaolinite and sub-poikilotopic Ca ankerite (late stage). The limestone paragenesis includes calcite cement (early stage); megaquartz, chalcedony, and Fe calcite spar (intermediate stage); and dissolution, Ca-Fe dolomite and kaolinite (late stage). The Rm value of vitrinite shows a regional average of 0.6-0.7%; Rock-Eval TmaX suggests a comparable degree of organic maturity. The Th of aqueous fluid inclusions in late stage Ca-Fe-Mg carbonates ranges from 90 to 160?? and Tmice indicates very saline water (>200000 ppm NaCl equivalent); ??18O suggests that the water is of basinal origin. Local warm spots have higher Rm, Tmax, and Th. The results constrain numerical models of regional fluid migration, which is widely viewed as an artesian flow from recharge areas in the Ouachita belt across the foreland basin onto the foreland shelf area. Such models must account for heating effects that extend at least 500 km from the orogenic front and affect both supposed aquifer beds and the overlying supposed confining layer. Warm spots indicate either more rapid or more prolonged flow locally. Th and Tmice data show the highest temperatures coincided with high salinity fluids. ?? 1995 Springer-Verlag.

Analysis of stem cell apheresis products using intermediate-dose filgrastim plus large volume apheresis for allogeneic transplantation.

PubMed

Engelhardt, M; Bertz, H; Wäsch, R; Finke, J

2001-04-01

Previously, a dose-dependent influence of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on CD34+ mobilization was demonstrated. In this single-center prospective analysis, 52 healthy donors were investigated to determine the efficacy of intermediate-dose rhG-CSF 2x8 microg/kg donor body weight (bw) and intermediate large volume apheresis (LVA, median 12 l) to mobilize peripheral blood progenitor cells (PBPC) for allogeneic transplantation. The median number of CD34+ cells in apheresis products was 0.45% and 2.2x10(6)/kg recipient bw per single apheresis. A total of 5.4x10(6)/kg CD34+ cells were collected with two (range: one to three) LVA. In the analysis of donor subgroups, higher peripheral blood (PB) and apheresis results were obtained in male vs female donors; however, donor weight significantly differed in both groups. Heavier donors displayed higher PB and apheresis CD34+ counts; however, when CD34+ cells/kg were adjusted to a constant bw, similar harvest results were calculated in males and females, demonstrating that gender per se does not, whereas bw does affect apheresis results. Younger donors had significantly higher PB CD34+ counts, higher CD34+ numbers per single apheresis, increased CFU, more T, B, and CD61+, comparable NK, and less CD14+ cells. A correlation analysis of donor age and apheresis results displayed an age-related decline of 0.46x10(6)/kg CD34 cells per decade of donor aging. Cell subsets in apheresis products were CD14 (49%), CD3 (22%), CD4 (13%), CD8 (7%), CD61 (20%), CD19 (5%), and CD16/56+ (3%) cells, with increasing CD14+ cells and decreasing CD3, CD4, CD8, CD61, CD19, and CD16/56+ cells on subsequent days of apheresis. Compared to our previous analysis using high- (2x12 microg) and low-dose (1x10 microg) rhG-CSF for allogeneic PBPC mobilization, the intermediate-dose showed a similar CD34+ mobilization potential to 1x10 microg rhG-CSF; however, with use of LVA, two instead of three (p<0.05) aphereses were sufficient to mobilize > or =4x10(6)/kg bw CD34+ cells in most donors. Taken together, our results demonstrate that intermediate-dose rhG-CSF sufficiently mobilizes > or =4x10(6)/kg x bw CD34+ cells with use of LVA and that especially younger donors display increased CD34+ cell numbers.

High-performance reconfigurable coincidence counting unit based on a field programmable gate array.

PubMed

Park, Byung Kwon; Kim, Yong-Su; Kwon, Osung; Han, Sang-Wook; Moon, Sung

2015-05-20

We present a high-performance reconfigurable coincidence counting unit (CCU) using a low-end field programmable gate array (FPGA) and peripheral circuits. Because of the flexibility guaranteed by the FPGA program, we can easily change system parameters, such as internal input delays, coincidence configurations, and the coincidence time window. In spite of a low-cost implementation, the proposed CCU architecture outperforms previous ones in many aspects: it has 8 logic inputs and 4 coincidence outputs that can measure up to eight-fold coincidences. The minimum coincidence time window and the maximum input frequency are 0.47 ns and 163 MHz, respectively. The CCU will be useful in various experimental research areas, including the field of quantum optics and quantum information.

In-beam spectroscopy of the k π=0- bands in230 236U

NASA Astrophysics Data System (ADS)

Zeyen, P.; Ackermann, B.; Dämmrich, U.; Euler, K.; Grafen, V.; Günther, C.; Herzog, P.; Marten-Tölle, M.; Prillwitz, B.; Tölle, R.; Lauterbach, Ch.; Maier, H. J.

1987-12-01

The K π=0- bands in even uranium nuclei were studied in the compound reactions231Pa( p, 2 n)230U,230, 232Th( α,2 n)232, 234U and236U( d, pn)236U. In-beam γ-rays were measured in coincidence with conversion-electrons, which were detected with an iron-free orange spectrometer. The negative-parity levels are observed up to intermediate spins ( I<13-). In addition, the 1- and 3- levels in230U were confirmed by a decay study with an isotope separated230Pa source. For the heavier isotopes ( A≥232) the properties of the K π=0- bands (energies and γ-branchings) are consistent with a vibrational character of these bands. For230U the K π=0- band lies at rather low energy ( E(1-)=367 keV), and the level spacings within this band are very similar to those of the isotones228Th and226Ra, which might indicate the onset of a stable octupole deformation.

Fast and controlled fabrication of porous graphene oxide: application of AFM tapping for mechano-chemistry

NASA Astrophysics Data System (ADS)

Chu, Liangyong; Korobko, Alexander V.; Bus, Marcel; Boshuizen, Bart; Sudhölter, Ernst J. R.; Besseling, Nicolaas A. M.

2018-05-01

This paper describes a novel method to fabricate porous graphene oxide (PGO) from GO by exposure to oxygen plasma. Compared to other methods to fabricate PGO described so far, e.g. the thermal and steam etching methods, oxygen plasma etching method is much faster. We studied the development of the porosity with exposure time using atomic force microscopy (AFM). It was found that the development of PGO upon oxygen-plasma exposure can be controlled by tapping mode AFM scanning using a Si tip. AFM tapping stalls the growth of pores upon further plasma exposure at a level that coincides with the fraction of sp2 carbons in the GO starting material. We suggest that AFM tapping procedure changes the bond structure of the intermediate PGO structure, and these stabilized PGO structures cannot be further etched by oxygen plasma. This constitutes the first report of tapping AFM as a tool for local mechano-chemistry.

Low-oxygen waters limited habitable space for early animals.

PubMed

Tostevin, R; Wood, R A; Shields, G A; Poulton, S W; Guilbaud, R; Bowyer, F; Penny, A M; He, T; Curtis, A; Hoffmann, K H; Clarkson, M O

2016-09-23

The oceans at the start of the Neoproterozoic Era (1,000-541 million years ago, Ma) were dominantly anoxic, but may have become progressively oxygenated, coincident with the rise of animal life. However, the control that oxygen exerted on the development of early animal ecosystems remains unclear, as previous research has focussed on the identification of fully anoxic or oxic conditions, rather than intermediate redox levels. Here we report anomalous cerium enrichments preserved in carbonate rocks across bathymetric basin transects from nine localities of the Nama Group, Namibia (∼550-541 Ma). In combination with Fe-based redox proxies, these data suggest that low-oxygen conditions occurred in a narrow zone between well-oxygenated surface waters and fully anoxic deep waters. Although abundant in well-oxygenated environments, early skeletal animals did not occupy oxygen impoverished regions of the shelf, demonstrating that oxygen availability (probably >10 μM) was a key requirement for the development of early animal-based ecosystems.

Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance.

PubMed

Koves, Timothy R; Ussher, John R; Noland, Robert C; Slentz, Dorothy; Mosedale, Merrie; Ilkayeva, Olga; Bain, James; Stevens, Robert; Dyck, Jason R B; Newgard, Christopher B; Lopaschuk, Gary D; Muoio, Deborah M

2008-01-01

Previous studies have suggested that insulin resistance develops secondary to diminished fat oxidation and resultant accumulation of cytosolic lipid molecules that impair insulin signaling. Contrary to this model, the present study used targeted metabolomics to find that obesity-related insulin resistance in skeletal muscle is characterized by excessive beta-oxidation, impaired switching to carbohydrate substrate during the fasted-to-fed transition, and coincident depletion of organic acid intermediates of the tricarboxylic acid cycle. In cultured myotubes, lipid-induced insulin resistance was prevented by manipulations that restrict fatty acid uptake into mitochondria. These results were recapitulated in mice lacking malonyl-CoA decarboxylase (MCD), an enzyme that promotes mitochondrial beta-oxidation by relieving malonyl-CoA-mediated inhibition of carnitine palmitoyltransferase 1. Thus, mcd(-/-) mice exhibit reduced rates of fat catabolism and resist diet-induced glucose intolerance despite high intramuscular levels of long-chain acyl-CoAs. These findings reveal a strong connection between skeletal muscle insulin resistance and lipid-induced mitochondrial stress.

Analog-to-digital conversion as a source of drifts in displacements derived from digital recordings of ground acceleration

USGS Publications Warehouse

Boore, D.M.

2003-01-01

Displacements obtained from double integration of digitally recorded ground accelerations often show drifts much larger than those expected for the true ground displacements. These drifts might be due to many things, including dynamic elastic ground tilt, inelastic ground deformation, hysteresis in the instruments, and cross feed due to misalignment of nominally orthogonal sensors. This article shows that even if those effects were not present, the analog-to-digital conversion (ADC) process can produce apparent "pulses" and offsets in the acceleration baseline if the ground motion is slowly varying compared with the quantization level of the digitization. Such slowly varying signals can be produced by constant offsets that do not coincide with a quantization level and by near- and intermediate-field terms in the wave field radiated from earthquakes. Double integration of these apparent pulses and offsets leads to drifts in the displacements similar to those found in processing real recordings. These effects decrease in importance as the resolution of the ADC process increases.

Neuropharmacology of brain-stimulation-evoked aggression.

PubMed

Siegel, A; Roeling, T A; Gregg, T R; Kruk, M R

1999-01-01

Evidence is reviewed concerning the brain areas and neurotransmitters involved in aggressive behavior in the cat and rodent. In the cat, two distinct neural circuits involving the hypothalamus and PAG subserve two different kinds of aggression: defensive rage and predatory (quiet-biting) attack. The roles played by the neurotransmitters serotonin, GABA, glutamate, opioids, cholecystokinin, substance P, norepinephrine, dopamine, and acetylcholine in the modulation and expression of aggression are discussed. For the rat, a single area, largely coincident with the intermediate hypothalamic area, is crucial for the expression of attack; variations in the rat attack response in natural settings are due largely to environmental variables. Experimental evidence emphasizing the roles of serotonin and GABA in modulating hypothalamically evoked attack in the rat is discussed. It is concluded that significant progress has been made concerning our knowledge of the circuitry underlying the neural basis of aggression. Although new and important insights have been made concerning neurotransmitter regulation of aggressive behavior, wide gaps in our knowledge remain.

Rag Deletion in Peripheral T Cells Blocks TCR Revision

PubMed Central

Hale, J. Scott; Ames, Kristina T.; Boursalian, Tamar E.; Fink, Pamela J.

2010-01-01

Mature CD4+Vβ5+ T cells that recognize a peripherally expressed endogenous superantigen are tolerized either by deletion or T cell receptor (TCR) revision. In Vβ5 transgenic mice, this latter tolerance pathway results in the appearance of CD4+Vβ5−TCRβ+ T cells, coinciding with Rag1, Rag2, and TdT expression and the accumulation of Vβ-DJβ recombination intermediates in peripheral CD4+ T cells. Because post-thymic RAG-dependent TCR rearrangement has remained controversial, we sought to definitively determine whether TCR revision is an extrathymic process that occurs in mature peripheral T cells. We now show that Rag deletion in post-positive selection T cells in Vβ5 transgenic mice blocks TCR revision in vivo, and that mature peripheral T cells sorted to remove cells bearing endogenous TCRβ chains can express newly generated TCRβ molecules in adoptive hosts. These findings unambiguously demonstrate post-thymic, RAG-dependent TCR rearrangement and define TCR revision as a tolerance pathway that targets mature peripheral CD4+ T cells. PMID:20435935

Cutting Edge: Rag deletion in peripheral T cells blocks TCR revision.

PubMed

Hale, J Scott; Ames, Kristina T; Boursalian, Tamar E; Fink, Pamela J

2010-06-01

Mature CD4(+)Vbeta5(+) T cells that recognize a peripherally expressed endogenous superantigen are tolerized either by deletion or TCR revision. In Vbeta5 transgenic mice, this latter tolerance pathway results in the appearance of CD4(+)Vbeta5(-)TCRbeta(+) T cells, coinciding with Rag1, Rag2, and TdT expression and the accumulation of V(beta)-DJ(beta) recombination intermediates in peripheral CD4(+) T cells. Because postthymic RAG-dependent TCR rearrangement has remained controversial, we sought to definitively determine whether TCR revision is an extrathymic process that occurs in mature peripheral T cells. We show in this study that Rag deletion in post-positive selection T cells in Vbeta5 transgenic mice blocks TCR revision in vivo and that mature peripheral T cells sorted to remove cells bearing endogenous TCRbeta-chains can express newly generated TCRbeta molecules in adoptive hosts. These findings unambiguously demonstrate postthymic, RAG-dependent TCR rearrangement and define TCR revision as a tolerance pathway that targets mature peripheral CD4(+) T cells.

Direct evidence of an incommensurate phase in NaNbO{sub 3} and its implication in NaNbO{sub 3}-based lead-free antiferroelectrics

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

Guo, Hanzheng; Randall, Clive A., E-mail: car4@psu.edu; Shimizu, Hiroyuki

2015-09-14

Hot-stage in situ transmission electron microscopy was employed to investigate the temperature-induced complex sequence of phase transitions in NaNbO{sub 3} polycrystalline. In addition to the commonly recognized P (Pbma) → R (Pmnm) → S (Pnmm) phase transitions, incommensurate phases were observed to exist in P and R phase regions. The former (in the P → R transition region) is coincident with a diffused dielectric peak appearing at ∼170 °C, and the latter (in the R → S transition region) serves as an intermediate structure to bridge the two sub-phases in the R phase region. The incommensurate phase in the P phasemore » region can be inferred from the polarization current density and differential dielectric permittivity anomalies, and it provides the bridge structure during the electric field-induced polarization reversal and antiferroelectric-to-ferroelectric transition in NaNbO{sub 3} solid solutions.« less

Fast and controlled fabrication of porous graphene oxide: application of AFM tapping for mechano-chemistry.

PubMed

Chu, Liangyong; Korobko, Alexander V; Bus, Marcel; Boshuizen, Bart; Sudhölter, Ernst J R; Besseling, Nicolaas A M

2018-05-04

This paper describes a novel method to fabricate porous graphene oxide (PGO) from GO by exposure to oxygen plasma. Compared to other methods to fabricate PGO described so far, e.g. the thermal and steam etching methods, oxygen plasma etching method is much faster. We studied the development of the porosity with exposure time using atomic force microscopy (AFM). It was found that the development of PGO upon oxygen-plasma exposure can be controlled by tapping mode AFM scanning using a Si tip. AFM tapping stalls the growth of pores upon further plasma exposure at a level that coincides with the fraction of sp 2 carbons in the GO starting material. We suggest that AFM tapping procedure changes the bond structure of the intermediate PGO structure, and these stabilized PGO structures cannot be further etched by oxygen plasma. This constitutes the first report of tapping AFM as a tool for local mechano-chemistry.

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

Saquet, N.; Holland, D. M. P.; Pratt, S. T.

We present photoelectron energy and angular distributions for resonant two-photon ionization via several low-lying Rydberg states of atomic Kr. The experiments were performed by using synchrotron radiation to pump the Rydberg states and a continuous-wave laser to probe them. Photoelectron images, recorded with both linear and circular polarized pump and probe light, were obtained in coincidence with mass-analyzed Kr ions. The photoelectron angular distributions and branching ratios for direct ionization into the Kr+ P-2(3/2) and P-2(1/2) spin-orbit continua show considerable dependence on the intermediate level, as well as on the polarizations of the pump and probe light. Photoelectron images weremore » also recorded with several polarization combinations following two-color excitation of the (P-2(1/2))5f[5/2](2) autoionizing resonance. These results are compared with the results of recent work on the corresponding autoionizing resonance in atomic Xe [E. V. Gryzlova et al., New J. Phys. 17, 043054 (2015)].« less

Vacuum Ultraviolet Photoionization of Complex Chemical Systems

DOE PAGES

Kostko, Oleg; Bandyopadhyay, Biswajit; Ahmed, Musahid

2016-02-24

Tunable vacuum ultraviolet (VUV) radiation coupled to mass spectrometry is applied to the study of complex chemical systems in this paper. The identification of novel reactive intermediates and radicals is revealed in flame, pulsed photolysis, and pyrolysis reactors, leading to the elucidation of spectroscopy, reaction mechanisms, and kinetics. Mass-resolved threshold photoelectron photoion coincidence measurements provide unprecedented access to vibrationally resolved spectra of free radicals present in high-temperature reactors. Photoionization measurements in water clusters, nucleic acid base dimers, and their complexes with water provide signatures of proton transfer in hydrogen-bonded and π-stacked systems. Experimental and theoretical methods to track ion–molecule reactionsmore » and fragmentation pathways in intermolecular and intramolecular hydrogen-bonded systems in sugars and alcohols are described. Photoionization of laser-ablated molecules, clusters, and their reaction products inform thermodynamics and spectroscopy that are relevant to astrochemistry and catalysis. Finally, new directions in coupling VUV radiation to interrogate complex chemical systems are discussed.« less

Primary Standardization of 152Eu by 4πβ(LS) – γ (Nal) coincidence counting and CIEMAT-NIST method

NASA Astrophysics Data System (ADS)

Ruzzarin, A.; da Cruz, P. A. L.; Ferreira Filho, A. L.; Iwahara, A.

2018-03-01

The 4πβ-γ coincidence counting and CIEMAT/NIST liquid scintillation method were used in the standardization of a solution of 152Eu. In CIEMAT/NIST method, measurements were performed in a Liquid Scintillation Counter model Wallac 1414. In the 4πβ-γ coincidence counting, the solution was standardized using a coincidence method with ‘‘beta-efficiency extrapolation”. A simple 4πβ-γ coincidence system was used, with acrylic scintillation cell coupled to two coincident photomultipliers at 180° each other and NaI(Tl) detector. The activity concentrations obtained were 156.934 ± 0.722 and 157.403 ± 0.113 kBq/g, respectively, for CIEMAT/NIST and 4πβ-γ coincidence counting measurement methods.

Protein Topology Determines Cysteine Oxidation Fate: The Case of Sulfenyl Amide Formation among Protein Families

PubMed Central

Defelipe, Lucas A.; Lanzarotti, Esteban; Gauto, Diego; Marti, Marcelo A.; Turjanski, Adrián G.

2015-01-01

Cysteine residues have a rich chemistry and play a critical role in the catalytic activity of a plethora of enzymes. However, cysteines are susceptible to oxidation by Reactive Oxygen and Nitrogen Species, leading to a loss of their catalytic function. Therefore, cysteine oxidation is emerging as a relevant physiological regulatory mechanism. Formation of a cyclic sulfenyl amide residue at the active site of redox-regulated proteins has been proposed as a protection mechanism against irreversible oxidation as the sulfenyl amide intermediate has been identified in several proteins. However, how and why only some specific cysteine residues in particular proteins react to form this intermediate is still unknown. In the present work using in-silico based tools, we have identified a constrained conformation that accelerates sulfenyl amide formation. By means of combined MD and QM/MM calculation we show that this conformation positions the NH backbone towards the sulfenic acid and promotes the reaction to yield the sulfenyl amide intermediate, in one step with the concomitant release of a water molecule. Moreover, in a large subset of the proteins we found a conserved beta sheet-loop-helix motif, which is present across different protein folds, that is key for sulfenyl amide production as it promotes the previous formation of sulfenic acid. For catalytic activity, in several cases, proteins need the Cysteine to be in the cysteinate form, i.e. a low pKa Cys. We found that the conserved motif stabilizes the cysteinate by hydrogen bonding to several NH backbone moieties. As cysteinate is also more reactive toward ROS we propose that the sheet-loop-helix motif and the constraint conformation have been selected by evolution for proteins that need a reactive Cys protected from irreversible oxidation. Our results also highlight how fold conservation can be correlated to redox chemistry regulation of protein function. PMID:25741692

Long-chain fatty acid combustion rate is associated with unique metabolite profiles in skeletal muscle mitochondria.

PubMed

Seifert, Erin L; Fiehn, Oliver; Bezaire, Véronic; Bickel, David R; Wohlgemuth, Gert; Adams, Sean H; Harper, Mary-Ellen

2010-03-24

Incomplete or limited long-chain fatty acid (LCFA) combustion in skeletal muscle has been associated with insulin resistance. Signals that are responsive to shifts in LCFA beta-oxidation rate or degree of intramitochondrial catabolism are hypothesized to regulate second messenger systems downstream of the insulin receptor. Recent evidence supports a causal link between mitochondrial LCFA combustion in skeletal muscle and insulin resistance. We have used unbiased metabolite profiling of mouse muscle mitochondria with the aim of identifying candidate metabolites within or effluxed from mitochondria and that are shifted with LCFA combustion rate. Large-scale unbiased metabolomics analysis was performed using GC/TOF-MS on buffer and mitochondrial matrix fractions obtained prior to and after 20 min of palmitate catabolism (n = 7 mice/condition). Three palmitate concentrations (2, 9 and 19 microM; corresponding to low, intermediate and high oxidation rates) and 9 microM palmitate plus tricarboxylic acid (TCA) cycle and electron transport chain inhibitors were each tested and compared to zero palmitate control incubations. Paired comparisons of the 0 and 20 min samples were made by Student's t-test. False discovery rate were estimated and Type I error rates assigned. Major metabolite groups were organic acids, amines and amino acids, free fatty acids and sugar phosphates. Palmitate oxidation was associated with unique profiles of metabolites, a subset of which correlated to palmitate oxidation rate. In particular, palmitate oxidation rate was associated with distinct changes in the levels of TCA cycle intermediates within and effluxed from mitochondria. This proof-of-principle study establishes that large-scale metabolomics methods can be applied to organelle-level models to discover metabolite patterns reflective of LCFA combustion, which may lead to identification of molecules linking muscle fat metabolism and insulin signaling. Our results suggest that future studies should focus on the fate of effluxed TCA cycle intermediates and on mechanisms ensuring their replenishment during LCFA metabolism in skeletal muscle.

Long-Chain Fatty Acid Combustion Rate Is Associated with Unique Metabolite Profiles in Skeletal Muscle Mitochondria

PubMed Central

Seifert, Erin L.; Fiehn, Oliver; Bezaire, Véronic; Bickel, David R.; Wohlgemuth, Gert; Adams, Sean H.; Harper, Mary-Ellen

2010-01-01

Background/Aim Incomplete or limited long-chain fatty acid (LCFA) combustion in skeletal muscle has been associated with insulin resistance. Signals that are responsive to shifts in LCFA β-oxidation rate or degree of intramitochondrial catabolism are hypothesized to regulate second messenger systems downstream of the insulin receptor. Recent evidence supports a causal link between mitochondrial LCFA combustion in skeletal muscle and insulin resistance. We have used unbiased metabolite profiling of mouse muscle mitochondria with the aim of identifying candidate metabolites within or effluxed from mitochondria and that are shifted with LCFA combustion rate. Methodology/Principal Findings Large-scale unbiased metabolomics analysis was performed using GC/TOF-MS on buffer and mitochondrial matrix fractions obtained prior to and after 20 min of palmitate catabolism (n = 7 mice/condition). Three palmitate concentrations (2, 9 and 19 µM; corresponding to low, intermediate and high oxidation rates) and 9 µM palmitate plus tricarboxylic acid (TCA) cycle and electron transport chain inhibitors were each tested and compared to zero palmitate control incubations. Paired comparisons of the 0 and 20 min samples were made by Student's t-test. False discovery rate were estimated and Type I error rates assigned. Major metabolite groups were organic acids, amines and amino acids, free fatty acids and sugar phosphates. Palmitate oxidation was associated with unique profiles of metabolites, a subset of which correlated to palmitate oxidation rate. In particular, palmitate oxidation rate was associated with distinct changes in the levels of TCA cycle intermediates within and effluxed from mitochondria. Conclusions/Significance This proof-of-principle study establishes that large-scale metabolomics methods can be applied to organelle-level models to discover metabolite patterns reflective of LCFA combustion, which may lead to identification of molecules linking muscle fat metabolism and insulin signaling. Our results suggest that future studies should focus on the fate of effluxed TCA cycle intermediates and on mechanisms ensuring their replenishment during LCFA metabolism in skeletal muscle. PMID:20352092

Factors associated with emergency medical services scope of practice for acute cardiovascular events.

PubMed

Williams, Ishmael; Valderrama, Amy L; Bolton, Patricia; Greek, April; Greer, Sophia; Patterson, Davis G; Zhang, Zefeng

2012-01-01

To examine prehospital emergency medical services (EMS) scope of practice for acute cardiovascular events and characteristics that may affect scope of practice; and to describe variations in EMS scope of practice for these events and the characteristics associated with that variability. In 2008, we conducted a telephone survey of 1,939 eligible EMS providers in nine states to measure EMS agency characteristics, medical director involvement, and 18 interventions authorized for prehospital care of acute cardiovascular events by three levels of emergency medical technician (EMT) personnel. A total of 1,292 providers responded to the survey, for a response rate of 67%. EMS scope of practice interventions varied by EMT personnel level, with the proportion of authorized interventions increasing as expected from EMT-Basic to EMT-Paramedic. Seven of eight statistically significant associations indicated that EMS agencies in urban settings were less likely to authorize interventions (odds ratios <0.7) for any level of EMS personnel. Based on the subset of six statistically significant associations, fire department-based EMS agencies were two to three times more likely to authorize interventions for EMT-Intermediate personnel. Volunteer EMS agencies were more than twice as likely as nonvolunteer agencies to authorize interventions for EMT-Basic and EMT-Intermediate personnel but were less likely to authorize any one of the 11 interventions for EMT-Paramedics. Greater medical director involvement was associated with greater likelihood of authorization of seven of the 18 interventions for EMT-Basic and EMT-Paramedic personnel but had no association with EMT-Intermediate personnel. We noted statistically significant variations in scope of practice by rural vs. urban setting, medical director involvement, and type of EMS service (fire department-based/non-fire department-based; volunteer/paid). These variations highlight local differences in the composition and capacity of EMS providers and offer important information for the transition towards the implementation of a national scope of practice model.

Trifocal intraocular lenses: a comparison of the visual performance and quality of vision provided by two different lens designs.

PubMed

Gundersen, Kjell G; Potvin, Rick

2017-01-01

To compare two different diffractive trifocal intraocular lens (IOL) designs, evaluating longer-term refractive outcomes, visual acuity (VA) at various distances, low contrast VA and quality of vision. Patients with binocularly implanted trifocal IOLs of two different designs (FineVision [FV] and Panoptix [PX]) were evaluated 6 months to 2 years after surgery. Best distance-corrected and uncorrected VA were tested at distance (4 m), intermediate (80 and 60 cm) and near (40 cm). A binocular defocus curve was collected with the subject's best distance correction in place. The preferred reading distance was determined along with the VA at that distance. Low contrast VA at distance was also measured. Quality of vision was measured with the National Eye Institute Visual Function Questionnaire near subset and the Quality of Vision questionnaire. Thirty subjects in each group were successfully recruited. The binocular defocus curves differed only at vergences of -1.0 D (FV better, P =0.02), -1.5 and -2.00 D (PX better, P <0.01 for both). Best distance-corrected and uncorrected binocular vision were significantly better for the PX lens at 60 cm ( P <0.01) with no significant differences at other distances. The preferred reading distance was between 42 and 43 cm for both lenses, with the VA at the preferred reading distance slightly better with the PX lens ( P =0.04). There were no statistically significant differences by lens for low contrast VA ( P =0.1) or for quality of vision measures ( P >0.3). Both trifocal lenses provided excellent distance, intermediate and near vision, but several measures indicated that the PX lens provided better intermediate vision at 60 cm. This may be important to users of tablets and other handheld devices. Quality of vision appeared similar between the two lens designs.

A Maximum NEC Criterion for Compton Collimation to Accurately Identify True Coincidences in PET

PubMed Central

Chinn, Garry; Levin, Craig S.

2013-01-01

In this work, we propose a new method to increase the accuracy of identifying true coincidence events for positron emission tomography (PET). This approach requires 3-D detectors with the ability to position each photon interaction in multi-interaction photon events. When multiple interactions occur in the detector, the incident direction of the photon can be estimated using the Compton scatter kinematics (Compton Collimation). If the difference between the estimated incident direction of the photon relative to a second, coincident photon lies within a certain angular range around colinearity, the line of response between the two photons is identified as a true coincidence and used for image reconstruction. We present an algorithm for choosing the incident photon direction window threshold that maximizes the noise equivalent counts of the PET system. For simulated data, the direction window removed 56%–67% of random coincidences while retaining > 94% of true coincidences from image reconstruction as well as accurately extracted 70% of true coincidences from multiple coincidences. PMID:21317079

Morphometric Identification of Queens, Workers and Intermediates in In Vitro Reared Honey Bees (Apis mellifera).

PubMed

De Souza, Daiana A; Wang, Ying; Kaftanoglu, Osman; De Jong, David; Amdam, Gro V; Gonçalves, Lionel S; Francoy, Tiago M

2015-01-01

In vitro rearing is an important and useful tool for honey bee (Apis mellifera L.) studies. However, it often results in intercastes between queens and workers, which are normally are not seen in hive-reared bees, except when larvae older than three days are grafted for queen rearing. Morphological classification (queen versus worker or intercastes) of bees produced by this method can be subjective and generally depends on size differences. Here, we propose an alternative method for caste classification of female honey bees reared in vitro, based on weight at emergence, ovariole number, spermatheca size and size and shape, and features of the head, mandible and basitarsus. Morphological measurements were made with both traditional morphometric and geometric morphometrics techniques. The classifications were performed by principal component analysis, using naturally developed queens and workers as controls. First, the analysis included all the characters. Subsequently, a new analysis was made without the information about ovariole number and spermatheca size. Geometric morphometrics was less dependent on ovariole number and spermatheca information for caste and intercaste identification. This is useful, since acquiring information concerning these reproductive structures requires time-consuming dissection and they are not accessible when abdomens have been removed for molecular assays or in dried specimens. Additionally, geometric morphometrics divided intercastes into more discrete phenotype subsets. We conclude that morphometric geometrics are superior to traditional morphometrics techniques for identification and classification of honey bee castes and intermediates.

Paradigm of pretest risk stratification before coronary computed tomography.

PubMed

Jensen, Jesper Møller; Ovrehus, Kristian A; Nielsen, Lene H; Jensen, Jesper K; Larsen, Henrik M; Nørgaard, Bjarne L

2009-01-01

The optimal method of determining the pretest risk of coronary artery disease as a patient selection tool before coronary multidetector computed tomography (MDCT) is unknown. We investigated the ability of 3 different clinical risk scores to predict the outcome of coronary MDCT. This was a retrospective study of 551 patients consecutively referred for coronary MDCT on a suspicion of coronary artery disease. Diamond-Forrester, Duke, and Morise risk models were used to predict coronary artery stenosis (>50%) as assessed by coronary MDCT. The models were compared by receiver operating characteristic analysis. The distribution of low-, intermediate-, and high-risk persons, respectively, was established and compared for each of the 3 risk models. Overall, all risk prediction models performed equally well. However, the Duke risk model classified the low-risk patients more correctly than did the other models (P < 0.01). In patients without coronary artery calcification (CAC), the predictive value of the Duke risk model was superior to the other risk models (P < 0.05). Currently available risk prediction models seem to perform better in patients without CAC. Between the risk prediction models, there was a significant discrepancy in the distribution of patients at low, intermediate, or high risk (P < 0.01). The 3 risk prediction models perform equally well, although the Duke risk score may have advantages in subsets of patients. The choice of risk prediction model affects the referral pattern to MDCT. Copyright (c) 2009 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Parp inhibition prevents ten-eleven translocase enzyme activation and hyperglycemia-induced DNA demethylation.

PubMed

Dhliwayo, Nyembezi; Sarras, Michael P; Luczkowski, Ernest; Mason, Samantha M; Intine, Robert V

2014-09-01

Studies from human cells, rats, and zebrafish have documented that hyperglycemia (HG) induces the demethylation of specific cytosines throughout the genome. We previously documented that a subset of these changes become permanent and may provide, in part, a mechanism for the persistence of complications referred to as the metabolic memory phenomenon. In this report, we present studies aimed at elucidating the molecular machinery that is responsible for the HG-induced DNA demethylation observed. To this end, RNA expression and enzymatic activity assays indicate that the ten-eleven translocation (Tet) family of enzymes are activated by HG. Furthermore, through the detection of intermediates generated via conversion of 5-methyl-cytosine back to the unmethylated form, the data were consistent with the use of the Tet-dependent iterative oxidation pathway. In addition, evidence is provided that the activity of the poly(ADP-ribose) polymerase (Parp) enzyme is required for activation of Tet activity because the use of a Parp inhibitor prevented demethylation of specific loci and the accumulation of Tet-induced intermediates. Remarkably, this inhibition was accompanied by a complete restoration of the tissue regeneration deficit that is also induced by HG. The ultimate goal of this work is to provide potential new avenues for therapeutic discovery. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Morphometric Identification of Queens, Workers and Intermediates in In Vitro Reared Honey Bees (Apis mellifera)

PubMed Central

A. De Souza, Daiana; Wang, Ying; Kaftanoglu, Osman; De Jong, David; V. Amdam, Gro; S. Gonçalves, Lionel; M. Francoy, Tiago

2015-01-01

In vitro rearing is an important and useful tool for honey bee (Apis mellifera L.) studies. However, it often results in intercastes between queens and workers, which are normally are not seen in hive-reared bees, except when larvae older than three days are grafted for queen rearing. Morphological classification (queen versus worker or intercastes) of bees produced by this method can be subjective and generally depends on size differences. Here, we propose an alternative method for caste classification of female honey bees reared in vitro, based on weight at emergence, ovariole number, spermatheca size and size and shape, and features of the head, mandible and basitarsus. Morphological measurements were made with both traditional morphometric and geometric morphometrics techniques. The classifications were performed by principal component analysis, using naturally developed queens and workers as controls. First, the analysis included all the characters. Subsequently, a new analysis was made without the information about ovariole number and spermatheca size. Geometric morphometrics was less dependent on ovariole number and spermatheca information for caste and intercaste identification. This is useful, since acquiring information concerning these reproductive structures requires time-consuming dissection and they are not accessible when abdomens have been removed for molecular assays or in dried specimens. Additionally, geometric morphometrics divided intercastes into more discrete phenotype subsets. We conclude that morphometric geometrics are superior to traditional morphometrics techniques for identification and classification of honey bee castes and intermediates. PMID:25894528

Asian Zika virus strains target CD14+ blood monocytes and induce M2-skewed immunosuppression during pregnancy

PubMed Central

Foo, Suan-Sin; Chen, Weiqiang; Chan, Yen; Bowman, James W.; Chang, Lin-Chun; Choi, Younho; Yoo, Ji Seung; Ge, Jianning; Cheng, Genhong; Bonnin, Alexandre; Nielsen-Saines, Karin; Brasil, Patrícia; Jung, Jae U.

2017-01-01

Blood CD14+ monocytes are the frontline immunomodulators categorized into classical, intermediate or non-classical subsets, subsequently differentiating into M1 pro- or M2 anti-inflammatory macrophages upon stimulation. While Zika virus (ZIKV) rapidly establishes viremia, the target cells and immune responses, particularly during pregnancy, remain elusive. Furthermore, it is unknown whether African- and Asian-lineage ZIKV have different phenotypic impacts on host immune responses. Using human blood infection, we identified CD14+ monocytes as the primary target for African- or Asian-lineage ZIKV infection. When immunoprofiles of human blood infected with ZIKV were compared, a classical/intermediate monocyte-mediated M1-skewed inflammation by African-lineage ZIKV infection was observed, in contrast to a non-classical monocyte-mediated M2-skewed immunosuppression by Asian-lineage ZIKV infection. Importantly, infection of pregnant women’s blood revealed enhanced susceptibility to ZIKV infection. Specifically, Asian-lineage ZIKV infection of pregnant women’s blood led to an exacerbated M2-skewed immunosuppression of non-classical monocytes in conjunction with global suppression of type I interferon-signaling pathway and an aberrant expression of host genes associated with pregnancy complications. 30 ZIKV+ sera from symptomatic pregnant patients also showed elevated levels of M2-skewed immunosuppressive cytokines and pregnancy complication-associated fibronectin-1. This study demonstrates the differential immunomodulatory responses of blood monocytes, particularly during pregnancy, upon infection with different lineages of ZIKV. PMID:28827581

Synergistic control of protein kinase Cgamma activity by ionotropic and metabotropic glutamate receptor inputs in hippocampal neurons.

PubMed

Codazzi, Franca; Di Cesare, Alessandra; Chiulli, Nino; Albanese, Alberto; Meyer, Tobias; Zacchetti, Daniele; Grohovaz, Fabio

2006-03-29

Conventional protein kinase C (PKC) isoforms are abundant neuronal signaling proteins with important roles in regulating synaptic plasticity and other neuronal processes. Here, we investigate the role of ionotropic and metabotropic glutamate receptor (iGluR and mGluR, respectively) activation on the generation of Ca2+ and diacylglycerol (DAG) signals and the subsequent activation of the neuron-specific PKCgamma isoform in hippocampal neurons. By combining Ca2+ imaging with total internal reflection microscopy analysis of specific biosensors, we show that elevation of both Ca2+ and DAG is necessary for sustained translocation and activation of EGFP (enhanced green fluorescent protein)-PKCgamma. Both DAG production and PKCgamma translocation were localized processes, typically observed within discrete microdomains along the dendritic branches. Markedly, intermediate-strength NMDA receptor (NMDAR) activation or moderate electrical stimulation generated Ca2+ but no DAG signals, whereas mGluR activation generated DAG but no Ca2+ signals. Both receptors were needed for PKCgamma activation. This suggests that a coincidence detection process exists between iGluRs and mGluRs that relies on a molecular coincidence detection process based on the corequirement of Ca2+ and DAG for PKCgamma activation. Nevertheless, the requirement for costimulation with mGluRs could be overcome for maximal NMDAR stimulation through a direct production of DAG via activation of the Ca2+-sensitive PLCdelta (phospholipase Cdelta) isoform. In a second important exception, mGluRs were sufficient for PKCgamma activation in neurons in which Ca2+ stores were loaded by previous electrical activity. Together, the dual activation requirement for PKCgamma provides a plausible molecular interpretation for different synergistic contributions of mGluRs to long-term potentiation and other synaptic plasticity processes.

Determining hydroclimatic extreme events over the south-central Andes

NASA Astrophysics Data System (ADS)

RamezaniZiarani, Maryam; Bookhagen, Bodo; Schmidt, Torsten; Wickert, Jens; de la Torre, Alejandro; Volkholz, Jan

2017-04-01

The south-central Andes in NW Argentina are characterized by a strong rainfall asymmetry. In the east-west direction exists one of the steepest rainfall gradients on Earth, resulting from the large topographic differences in this region. In addition, in the north-south direction the rainfall intensity varies as the climatic regime shifts from the tropical central Andes to the subtropical south-central Andes. In this study, we investigate hydroclimatic extreme events over the south-central Andes using ERA-Interim reanalysis data of the ECMWF (European Centre for Medium-Range Weather Forecasts), the high resolution regional climate model (COSMO-CLM) data and TRMM (Tropical Rainfall Measuring Mission) data. We divide the area in three different study regions based on elevation: The high-elevation Altiplano-Puna plateau, an intermediate area characterized by intramontane basins, and the foreland area. We analyze the correlations between climatic variables, such as specific humidity, zonal wind component, meridional wind component and extreme rainfall events in all three domains. The results show that there is a high positive temporal correlation between extreme rainfall events (90th and 99th percentile rainfall) and extreme specific humidity events (90th and 99th percentile specific humidity). In addition, the temporal variations analysis represents a trend of increasing specific humidity with time during time period (1994-2013) over the Altiplano-Puna plateau which is in agreement with rainfall trend. Regarding zonal winds, our results indicate that 99th percentile rainfall events over the Altiplano-Puna plateau coincide temporally with strong easterly winds from intermountain and foreland regions in the east. In addition, the results regarding the meridional wind component represent strong northerly winds in the foreland region coincide temporally with 99th percentile rainfall over the Altiplano-Puna plateau.

Dueling Deglacial Depth Transects: A Synthesis of Isotope Records from the South Atlantic and Pacific Oceans Provides Insight into Deglacial Ocean Circulation

NASA Astrophysics Data System (ADS)

Sikes, E. L.; Allen, K. A.; Lund, D. C.

2016-12-01

The end of the last ice age was marked by rapid increases in atmospheric CO2 and changes in ocean circulation and seawater δ13C and Δ14C, suggesting that enhanced ventilation of the deep ocean may have released sequestered CO2 to the atmosphere. Here we compare depth transects of Δ14C and high-resolution Cibicidoides sp. δ13C and δ18O records from the Southwest Pacific and the Southwest Atlantic to gain insight into the changing extent and composition of water masses in the Southern Hemisphere. Our vertical transects document that during the Last Glacial Maximum (LGM), water mass properties and boundaries in the Southwest Atlantic and Pacific were very different from one another and from their respective modern profiles. The shallow to deep δ13C difference (Δδ13C, 660- 2500 m) in the Pacific was 1.7‰, more than double the Holocene value ( 0.7‰) and a deep watermass boundary was situated above 1600m. LGM Δδ13C in the Atlantic was similar to the Pacific, but the deep geochemical front was situated at 2500 m (as observed previously; e.g. Hoffman and Lund, 2012). At the onset of Heinrich Stadial 1 (HS1; 18 - 14.5 ka), changes in the shallow isotope records (< 1500 m) from the two basins differed, indicating independent controls on intermediate water composition/formation in these two ocean basins. During HS1 in the Pacific, rapid δ13C and Δ14C enrichment above 1600 m coincided with δ13C depletion in Atlantic waters between 1500 m and 2500 m. Benthic δ13C below 2500 m in both basins and D14C in the Pacific remained depleted until the Antarctic Cold Reversal (ACR; 14.7 to 12.7 ka). During the ACR, Pacific Δ14C below 1600 m increased while both the Atlantic and Pacific experienced a rapid increase in δ13C and decrease in δ18O below 2500 m. These simultaneous isotopic shifts in the Pacific and Atlantic support the idea of a widespread pulse of deep-water ventilation driven by the resumption of North Atlantic Deep Water formation during the ACR. Overall, early shallow to intermediate ventilation differed between the two basins and simultaneous deep ventilation occurred later in the deglaciation, coincident with the reinitiation of deep overturning circulation during the Bølling-Allerød.

Influence of the post-Miocene tectonic activity on the geomorphology between Andes and Pampa Deprimida in the area of Provincia de La Pampa, Argentina

NASA Astrophysics Data System (ADS)

Vogt, Henri; Vogt, Thea; Calmels, Augusto P.

2010-09-01

The genesis of the relief between the Andes and the Pampa Deprimida plain between 36° and 39°S has never been considered. The region is intermediate between two contrasting geomorphic styles, the meridian-oriented highs and depressions of the Sierras Pampeanas to the north and the eastwards sloping northern Patagonian mesetas to the south. From geophysical data, it coincides with an intermediate zone between a flat-slab subduction zone to the north and a normal subduction zone to the south. From west to east (68° to 64°W), four units follow each other: the easternmost portion of the Sub-Andean piedmont, the depression of the Río Chadileuvú, a Plateau, and a high scarp separating it from the Pampa Deprimida lowland. The Plateau is the southernmost portion of the Brazilian shield. Geomorphological and sedimentological analyses led us to the following conclusions: 1. the Andes uplift created a large piedmont reaching the Pampa Deprimida and including the Plateau which between the Pliocene and the Middle Pleistocene was shaped in a series of stepped levels covered by Andean fluvial sediments; 2. the meridian-oriented Rio Chadileuvú depression is of tectonic origin, younger than the Middle Pleistocene, and breaks the continuity between the piedmont and the Plateau: this depression could be an incipient foreland basin; 3. the eastern scarp is a fault scarp, probably Upper Pleistocene in age, due to a faster activity of the fault zone between the craton and the Macachín Trough. This young morphotectonic activity coincides with the change from a west-east Patagonian pattern to a north-south orientation of the relief typical of the Sierras Pampeanas, but younger than them. The river network was affected by this evolution. During the Upper Miocene, a palaeo-Río Negro flowed to the north-east, then shifted southwards. The Río Colorado entered the Pampa region during the Upper Pliocene creating a set of stepped fluvial accumulation terraces, while the piedmont was drained by eastward streams. Following the formation of the Chadileuvú depression, a north-south drainage, largely endoreic, replaced the Sub-Andean flows. A capture of the Río Chadileuvú by the Río Colorado is going on due to the incision of the Río Colorado in the south. The regional landscape is therefore directly related to Late Pleistocene tectonic activity, whereas climate changes explain the different sedimentary characteristics of the surficial deposits.

Breaking through the false coincidence barrier in electron–ion coincidence experiments

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

Osborn, David L.; Hayden, Carl C.; Hemberger, Patrick

Photoelectron Photoion Coincidence (PEPICO) spectroscopy holds the promise of a universal, isomer-selective, and sensitive analytical technique for time-resolved quantitative analysis of bimolecular chemical reactions. Unfortunately, its low dynamic range of ~10 3 has largely precluded its use for this purpose, where a dynamic range of at least 10 5 is generally required. This limitation is due to the false coincidence background common to all coincidence experiments, especially at high count rates. Electron/ion pairs emanating from separate ionization events but arriving within the ion time of flight (TOF) range of interest constitute the false coincidence background. Although this background has uniformmore » intensity at every m/z value, the Poisson scatter in the false coincidence background obscures small signals. In this paper, temporal ion deflection coupled with a position-sensitive ion detector enables suppression of the false coincidence background, increasing the dynamic range in the PEPICO TOF mass spectrum by 2–3 orders of magnitude. The ions experience a time-dependent electric deflection field at a well-defined fraction of their time of flight. This deflection defines an m/z- and ionization-time dependent ion impact position for true coincidences, whereas false coincidences appear randomly outside this region and can be efficiently suppressed. When cold argon clusters are ionized, false coincidence suppression allows us to observe species up to Ar 9 +, whereas Ar 4 + is the largest observable cluster under traditional operation. As a result, this advance provides mass-selected photoelectron spectra for fast, high sensitivity quantitative analysis of reacting systems.« less

Breaking through the false coincidence barrier in electron–ion coincidence experiments

DOE PAGES

Osborn, David L.; Hayden, Carl C.; Hemberger, Patrick; ...

2016-10-31

Photoelectron Photoion Coincidence (PEPICO) spectroscopy holds the promise of a universal, isomer-selective, and sensitive analytical technique for time-resolved quantitative analysis of bimolecular chemical reactions. Unfortunately, its low dynamic range of ~10 3 has largely precluded its use for this purpose, where a dynamic range of at least 10 5 is generally required. This limitation is due to the false coincidence background common to all coincidence experiments, especially at high count rates. Electron/ion pairs emanating from separate ionization events but arriving within the ion time of flight (TOF) range of interest constitute the false coincidence background. Although this background has uniformmore » intensity at every m/z value, the Poisson scatter in the false coincidence background obscures small signals. In this paper, temporal ion deflection coupled with a position-sensitive ion detector enables suppression of the false coincidence background, increasing the dynamic range in the PEPICO TOF mass spectrum by 2–3 orders of magnitude. The ions experience a time-dependent electric deflection field at a well-defined fraction of their time of flight. This deflection defines an m/z- and ionization-time dependent ion impact position for true coincidences, whereas false coincidences appear randomly outside this region and can be efficiently suppressed. When cold argon clusters are ionized, false coincidence suppression allows us to observe species up to Ar 9 +, whereas Ar 4 + is the largest observable cluster under traditional operation. As a result, this advance provides mass-selected photoelectron spectra for fast, high sensitivity quantitative analysis of reacting systems.« less

Systemic immune response and virus persistence after foot-and-mouth disease virus infection of naïve cattle and cattle vaccinated with a homologous adenovirus-vectored vaccine

DOE PAGES

Eschbaumer, Michael; Stenfeldt, Carolina; Rekant, Steven I.; ...

2016-09-15

In order to investigate host factors associated with the establishment of persistent foot-and-mouth disease virus (FMDV) infection, the systemic response to vaccination and challenge was studied in 47 steers. Eighteen steers that had received a recombinant FMDV A vaccine 2 weeks earlier and 29 non-vaccinated steers were challenged by intra-nasopharyngeal deposition of FMDV A24. For up to 35 days after challenge, host factors including complete blood counts with T lymphocyte subsets, type I/III interferon (IFN) activity, neutralizing and total FMDV-specific antibody titers in serum, as well as antibody-secreting cells (in 6 non-vaccinated animals) were characterized in the context of viralmore » infection dynamics. As a result, vaccination generally induced a strong antibody response. There was a transient peak of FMDV-specific serum IgM in non-vaccinated animals after challenge, while IgM levels in vaccinated animals did not increase further. Both groups had a lasting increase of specific IgG and neutralizing antibody after challenge. Substantial systemic IFN activity in non-vaccinated animals coincided with viremia, and no IFN or viremia was detected in vaccinated animals. After challenge, circulating lymphocytes decreased in non-vaccinated animals, coincident with viremia, IFN activity, and clinical disease, whereas lymphocyte and monocyte counts in vaccinated animals were unaffected by vaccination but transiently increased after challenge. The CD4 +/CD8 + T cell ratio in non-vaccinated animals increased during acute infection, driven by an absolute decrease of CD8 + cells. In conclusion, the incidence of FMDV persistence was 61.5 % in non-vaccinated and 54.5 % in vaccinated animals. Overall, the systemic factors examined were not associated with the FMDV carrier/non-carrier divergence; however, significant differences were identified between responses of non-vaccinated and vaccinated cattle.« less

Bubble nasal CPAP, early surfactant treatment, and rapid extubation are associated with decreased incidence of bronchopulmonary dysplasia in very-low-birth-weight newborns: efficacy and safety considerations.

PubMed

Friedman, Charles A; Menchaca, Robert C; Baker, Mary C; Rivas, Clarissa K; Laberge, Raymond N; Rios, Enrique H; Haider, Syed H; Romero, Edgar J; Eason, Elizabeth B; Fraley, J Kennard; Woldesenbet, Mesfin

2013-07-01

Current literature has been inconsistent in demonstrating that minimizing the duration of mechanical ventilation in very-low-birth-weight (VLBW) newborns reduces lung damage. To determine if introduction of bubble nasal CPAP (bnCPAP), early surfactant treatment, and rapid extubation (combined bnCPAP strategy) in our community-based neonatal ICU reduced bronchopulmonary dysplasia (BPD). This was a 7-year retrospective,single-institution review of respiratory outcomes in 633 VLBW babies before and after introduction of the combined bnCPAP strategy. Coincident changes in newborn care were taken into account with a logistic regression model. The average percentage of VLBW newborns with BPD decreased to 25.8% from 35.4% (P = .02), reaching a minimum in the last post-bnCPAP year of22.1% (P = .02). When other coincident changes in newborn care during the study years were taken into account, VLBW babies in the post-bnCPAP years had a 43% lower chance of developing BPD(P = .003, odds ratio 0.43, 95% CI 0.25– 0.75). Decreases occurred in mechanical ventilation and the percentage of infants discharged on diuretics and on supplemental oxygen. Among the subset of extremely-low-birth-weight newborns, improved respiratory outcomes in the post-bnCPAP years,as compared to outcomes in the pre-bnCPAP years, included an increase in the percentage alive and off mechanical ventilation at 1 week postnatal age (P < .001), a more rapid extubation rate(P < .03), a decrease in the median days on mechanical ventilation (P = .002), and a decrease in the percentage with BPD plus died (P = .01). Post-bnCPAP extremely-low-birth-weight babies had a statistically significant decrease in retinopathy of prematurity, an increase in low-grade intraventricular hemorrhage, and a decrease in ductal ligations. A combined BnCPAP strategy may contribute to a reduction of BPD, after adjusting for concurrent treatments.

Systemic immune response and virus persistence after foot-and-mouth disease virus infection of naïve cattle and cattle vaccinated with a homologous adenovirus-vectored vaccine

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

Eschbaumer, Michael; Stenfeldt, Carolina; Rekant, Steven I.

In order to investigate host factors associated with the establishment of persistent foot-and-mouth disease virus (FMDV) infection, the systemic response to vaccination and challenge was studied in 47 steers. Eighteen steers that had received a recombinant FMDV A vaccine 2 weeks earlier and 29 non-vaccinated steers were challenged by intra-nasopharyngeal deposition of FMDV A24. For up to 35 days after challenge, host factors including complete blood counts with T lymphocyte subsets, type I/III interferon (IFN) activity, neutralizing and total FMDV-specific antibody titers in serum, as well as antibody-secreting cells (in 6 non-vaccinated animals) were characterized in the context of viralmore » infection dynamics. As a result, vaccination generally induced a strong antibody response. There was a transient peak of FMDV-specific serum IgM in non-vaccinated animals after challenge, while IgM levels in vaccinated animals did not increase further. Both groups had a lasting increase of specific IgG and neutralizing antibody after challenge. Substantial systemic IFN activity in non-vaccinated animals coincided with viremia, and no IFN or viremia was detected in vaccinated animals. After challenge, circulating lymphocytes decreased in non-vaccinated animals, coincident with viremia, IFN activity, and clinical disease, whereas lymphocyte and monocyte counts in vaccinated animals were unaffected by vaccination but transiently increased after challenge. The CD4 +/CD8 + T cell ratio in non-vaccinated animals increased during acute infection, driven by an absolute decrease of CD8 + cells. In conclusion, the incidence of FMDV persistence was 61.5 % in non-vaccinated and 54.5 % in vaccinated animals. Overall, the systemic factors examined were not associated with the FMDV carrier/non-carrier divergence; however, significant differences were identified between responses of non-vaccinated and vaccinated cattle.« less

A morphing-based scheme for large deformation analysis with stereo-DIC

NASA Astrophysics Data System (ADS)

Genovese, Katia; Sorgente, Donato

2018-05-01

A key step in the DIC-based image registration process is the definition of the initial guess for the non-linear optimization routine aimed at finding the parameters describing the pixel subset transformation. This initialization may result very challenging and possibly fail when dealing with pairs of largely deformed images such those obtained from two angled-views of not-flat objects or from the temporal undersampling of rapidly evolving phenomena. To address this problem, we developed a procedure that generates a sequence of intermediate synthetic images for gradually tracking the pixel subset transformation between the two extreme configurations. To this scope, a proper image warping function is defined over the entire image domain through the adoption of a robust feature-based algorithm followed by a NURBS-based interpolation scheme. This allows a fast and reliable estimation of the initial guess of the deformation parameters for the subsequent refinement stage of the DIC analysis. The proposed method is described step-by-step by illustrating the measurement of the large and heterogeneous deformation of a circular silicone membrane undergoing axisymmetric indentation. A comparative analysis of the results is carried out by taking as a benchmark a standard reference-updating approach. Finally, the morphing scheme is extended to the most general case of the correspondence search between two largely deformed textured 3D geometries. The feasibility of this latter approach is demonstrated on a very challenging case: the full-surface measurement of the severe deformation (> 150% strain) suffered by an aluminum sheet blank subjected to a pneumatic bulge test.

Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein

PubMed Central

Kakalacheva, Kristina; Regenass, Stephan; Wiesmayr, Silke; Azzi, Tarik; Berger, Christoph; Dale, Russell C.; Brilot, Fabienne; Münz, Christian; Rostasy, Kevin; Nadal, David; Lünemann, Jan D.

2016-01-01

A history of infectious mononucleosis (IM), symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses. Antibody responses towards cellular antigens using a HEp-2 based indirect immunofluorescence assay and native myelin oligodendrocyte glycoprotein (MOG) using a flow cytometry-based assay were determined in 35 patients with IM and in 23 control subjects. We detected frequent immunoglobulin M (IgM) reactivity to vimentin, a major constituent of the intermediate filament family of proteins, in IM patients (27/35; 77%) but rarely in control subjects (2/23; 9%). IgG autoantibodies binding to HEp-2 cells were absent in both groups. In contrast, IgG responses to native MOG, present in up to 40% of children with inflammatory demyelinating diseases of the central nervous system (CNS), were detectable in 7/35 (20%) patients with IM but not in control subjects. Normalization of anti-vimentin IgM levels to increased total IgM concentrations during IM resulted in loss of significant differences for anti-vimentin IgM titers. Anti-MOG specific IgG responses were still detectable in a subset of three out of 35 patients with IM (9%), even after normalization to increased total IgG levels. Vimentin-specific IgM and MOG-specific IgG responses decreased following clinical resolution of acute IM symptoms. We conclude from our data that MOG-specific memory B cells are activated in subset of patients with IM. PMID:26907324

Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein.

PubMed

Kakalacheva, Kristina; Regenass, Stephan; Wiesmayr, Silke; Azzi, Tarik; Berger, Christoph; Dale, Russell C; Brilot, Fabienne; Münz, Christian; Rostasy, Kevin; Nadal, David; Lünemann, Jan D

2016-02-12

A history of infectious mononucleosis (IM), symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses. Antibody responses towards cellular antigens using a HEp-2 based indirect immunofluorescence assay and native myelin oligodendrocyte glycoprotein (MOG) using a flow cytometry-based assay were determined in 35 patients with IM and in 23 control subjects. We detected frequent immunoglobulin M (IgM) reactivity to vimentin, a major constituent of the intermediate filament family of proteins, in IM patients (27/35; 77%) but rarely in control subjects (2/23; 9%). IgG autoantibodies binding to HEp-2 cells were absent in both groups. In contrast, IgG responses to native MOG, present in up to 40% of children with inflammatory demyelinating diseases of the central nervous system (CNS), were detectable in 7/35 (20%) patients with IM but not in control subjects. Normalization of anti-vimentin IgM levels to increased total IgM concentrations during IM resulted in loss of significant differences for anti-vimentin IgM titers. Anti-MOG specific IgG responses were still detectable in a subset of three out of 35 patients with IM (9%), even after normalization to increased total IgG levels. Vimentin-specific IgM and MOG-specific IgG responses decreased following clinical resolution of acute IM symptoms. We conclude from our data that MOG-specific memory B cells are activated in subset of patients with IM.

Phenylbutyrate therapy for maple syrup urine disease

PubMed Central

Brunetti-Pierri, Nicola; Lanpher, Brendan; Erez, Ayelet; Ananieva, Elitsa A.; Islam, Mohammad; Marini, Juan C.; Sun, Qin; Yu, Chunli; Hegde, Madhuri; Li, Jun; Wynn, R. Max; Chuang, David T.; Hutson, Susan; Lee, Brendan

2011-01-01

Therapy with sodium phenylacetate/benzoate or sodium phenylbutyrate in urea cycle disorder patients has been associated with a selective reduction in branched-chain amino acids (BCAA) in spite of adequate dietary protein intake. Based on this clinical observation, we investigated the potential of phenylbutyrate treatment to lower BCAA and their corresponding α-keto acids (BCKA) in patients with classic and variant late-onset forms of maple syrup urine disease (MSUD). We also performed in vitro and in vivo experiments to elucidate the mechanism for this effect. We found that BCAA and BCKA are both significantly reduced following phenylbutyrate therapy in control subjects and in patients with late-onset, intermediate MSUD. In vitro treatment with phenylbutyrate of control fibroblasts and lymphoblasts resulted in an increase in the residual enzyme activity, while treatment of MSUD cells resulted in the variable response which did not simply predict the biochemical response in the patients. In vivo phenylbutyrate increases the proportion of active hepatic enzyme and unphosphorylated form over the inactive phosphorylated form of the E1α subunit of the branched-chain α-keto acid dehydrogenase complex (BCKDC). Using recombinant enzymes, we show that phenylbutyrate prevents phosphorylation of E1α by inhibition of the BCKDC kinase to activate BCKDC overall activity, providing a molecular explanation for the effect of phenylbutyrate in a subset of MSUD patients. Phenylbutyrate treatment may be a valuable treatment for reducing the plasma levels of neurotoxic BCAA and their corresponding BCKA in a subset of MSUD patients and studies of its long-term efficacy are indicated. PMID:21098507

Phenylbutyrate therapy for maple syrup urine disease.

PubMed

Brunetti-Pierri, Nicola; Lanpher, Brendan; Erez, Ayelet; Ananieva, Elitsa A; Islam, Mohammad; Marini, Juan C; Sun, Qin; Yu, Chunli; Hegde, Madhuri; Li, Jun; Wynn, R Max; Chuang, David T; Hutson, Susan; Lee, Brendan

2011-02-15

Therapy with sodium phenylacetate/benzoate or sodium phenylbutyrate in urea cycle disorder patients has been associated with a selective reduction in branched-chain amino acids (BCAA) in spite of adequate dietary protein intake. Based on this clinical observation, we investigated the potential of phenylbutyrate treatment to lower BCAA and their corresponding α-keto acids (BCKA) in patients with classic and variant late-onset forms of maple syrup urine disease (MSUD). We also performed in vitro and in vivo experiments to elucidate the mechanism for this effect. We found that BCAA and BCKA are both significantly reduced following phenylbutyrate therapy in control subjects and in patients with late-onset, intermediate MSUD. In vitro treatment with phenylbutyrate of control fibroblasts and lymphoblasts resulted in an increase in the residual enzyme activity, while treatment of MSUD cells resulted in the variable response which did not simply predict the biochemical response in the patients. In vivo phenylbutyrate increases the proportion of active hepatic enzyme and unphosphorylated form over the inactive phosphorylated form of the E1α subunit of the branched-chain α-keto acid dehydrogenase complex (BCKDC). Using recombinant enzymes, we show that phenylbutyrate prevents phosphorylation of E1α by inhibition of the BCKDC kinase to activate BCKDC overall activity, providing a molecular explanation for the effect of phenylbutyrate in a subset of MSUD patients. Phenylbutyrate treatment may be a valuable treatment for reducing the plasma levels of neurotoxic BCAA and their corresponding BCKA in a subset of MSUD patients and studies of its long-term efficacy are indicated.

Prediction of Response to Preoperative Chemoradiotherapy in Rectal Cancer by Multiplex Kinase Activity Profiling

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

Folkvord, Sigurd; Flatmark, Kjersti; Department of Cancer and Surgery, Norwegian Radium Hospital, Oslo University Hospital

2010-10-01

Purpose: Tumor response of rectal cancer to preoperative chemoradiotherapy (CRT) varies considerably. In experimental tumor models and clinical radiotherapy, activity of particular subsets of kinase signaling pathways seems to predict radiation response. This study aimed to determine whether tumor kinase activity profiles might predict tumor response to preoperative CRT in locally advanced rectal cancer (LARC). Methods and Materials: Sixty-seven LARC patients were treated with a CRT regimen consisting of radiotherapy, fluorouracil, and, where possible, oxaliplatin. Pretreatment tumor biopsy specimens were analyzed using microarrays with kinase substrates, and the resulting substrate phosphorylation patterns were correlated with tumor response to preoperative treatmentmore » as assessed by histomorphologic tumor regression grade (TRG). A predictive model for TRG scores from phosphosubstrate signatures was obtained by partial-least-squares discriminant analysis. Prediction performance was evaluated by leave-one-out cross-validation and use of an independent test set. Results: In the patient population, 73% and 15% were scored as good responders (TRG 1-2) or intermediate responders (TRG 3), whereas 12% were assessed as poor responders (TRG 4-5). In a subset of 7 poor responders and 12 good responders, treatment outcome was correctly predicted for 95%. Application of the prediction model on the remaining patient samples resulted in correct prediction for 85%. Phosphosubstrate signatures generated by poor-responding tumors indicated high kinase activity, which was inhibited by the kinase inhibitor sunitinib, and several discriminating phosphosubstrates represented proteins derived from signaling pathways implicated in radioresistance. Conclusions: Multiplex kinase activity profiling may identify functional biomarkers predictive of tumor response to preoperative CRT in LARC.« less

Intermediate filament protein evolution and protists.

PubMed

Preisner, Harald; Habicht, Jörn; Garg, Sriram G; Gould, Sven B

2018-03-23

Metazoans evolved from a single protist lineage. While all eukaryotes share a conserved actin and tubulin-based cytoskeleton, it is commonly perceived that intermediate filaments (IFs), including lamin, vimentin or keratin among many others, are restricted to metazoans. Actin and tubulin proteins are conserved enough to be detectable across all eukaryotic genomes using standard phylogenetic methods, but IF proteins, in contrast, are notoriously difficult to identify by such means. Since the 1950s, dozens of cytoskeletal proteins in protists have been identified that seemingly do not belong to any of the IF families described for metazoans, yet, from a structural and functional perspective fit criteria that define metazoan IF proteins. Here, we briefly review IF protein discovery in metazoans and the implications this had for the definition of this protein family. We argue that the many cytoskeletal and filament-forming proteins of protists should be incorporated into a more comprehensive picture of IF evolution by aligning it with the recent identification of lamins across the phylogenetic diversity of eukaryotic supergroups. This then brings forth the question of how the diversity of IF proteins has unfolded. The evolution of IF proteins likely represents an example of convergent evolution, which, in combination with the speed with which these cytoskeletal proteins are evolving, generated their current diversity. IF proteins did not first emerge in metazoa, but in protists. Only the emergence of cytosolic IF proteins that appear to stem from a nuclear lamin is unique to animals and coincided with the emergence of true animal multicellularity. © 2018 Wiley Periodicals, Inc.

The intermediate-depth Tonga double-seismic zone and relationship to slab thermal structure

NASA Astrophysics Data System (ADS)

Wei, S. S.; Wiens, D.; Van Keken, P. E.; Adams, A. N.; Cai, C.

2015-12-01

We used data from the ocean bottom seismographs and island-based stations deployed in the Tonga-Fiji area from 2009 to 2010 to investigate the seismicity of the Tonga subducting slab. We relocated 785 events from the Reviewed ISC Bulletin with local array data, 379 newly detected intermediate-depth events, as well as 1976-2012 events with Global Centroid-Moment-Tensor (CMT) solutions. The events were relocated with both local and teleseismic P, pP, and S arrivals using a hypocentroidal decomposition relative location algorithm. The results show a double-seismic zone (DSZ) with a separation of about 30 km along the Tonga slab within a depth range of about 70 - 300 km. The upper plane is more seismically active and characterized by downdip compressional stress whereas the lower plane is characterized by downdip tensional stress, consistent with the slab unbending model. Accordingly, focal mechanisms of the earthquakes along the surface of the slab show downdip extension above the depth of 80 km, but turn to compression below it, coinciding with the change of the slab dip angle from 30˚ to 60˚ at the same depth. The lower limit of the DSZ beneath Tonga is significantly deeper than that in Japan and Mariana (about 200 km), implying the importance of thermal variations in controlling the DSZ. Since the Tonga slab, with the fastest subduction rate, is cooler than other slabs, thermally controlled processes such as dehydration embrittlement can occur at greater depths, resulting in a deeper depth extent of the DSZ.

Ascorbic Acid Metabolism in Pea Seedlings. A Comparison of d-Glucosone, l-Sorbosone, and l-Galactono-1,4-Lactone as Ascorbate Precursors1

PubMed Central

Pallanca, Jane E.; Smirnoff, Nicholas

1999-01-01

l-Ascorbic acid (AsA) accumulates in pea (Pisum sativum L.) seedlings during germination, with the most rapid phase of accumulation coinciding with radicle emergence. Monodehydroascorbate reductase and dehydroascorbic acid reductase were active in the embryonic axes before AsA accumulation started, whereas AsA oxidase and AsA peroxidase activities increased in parallel with AsA. Excised embryonic axes were used to investigate the osone pathway of AsA biosynthesis, in which d-glucosone and l-sorbosone are the proposed intermediates. [U-14C]Glucosone was incorporated into AsA and inhibited the incorporation of [U-14C]glucose (Glc) into AsA. A higher d-glucosone concentration (5 mm) inhibited AsA accumulation. l-Sorbosone did not affect AsA pool size but caused a small inhibition in the incorporation of [U-14C]Glc into AsA. Oxidase and dehydrogenase activities capable of converting Glc or Glc-6-phosphate to glucosone were not detected in embryonic axis extracts. The osones are therefore unlikely to be physiological intermediates of AsA biosynthesis. l-Galactono-1,4-lactone, recently proposed as the AsA precursor (G.L. Wheeler, M.A. Jones, N. Smirnoff [1998] Nature 393: 365–369), was readily converted to AsA by pea embryonic axes. Although l-galactono-1,4-lactone did not inhibit [14C]Glc incorporation into AsA, this does not mean that it is not a precursor, because competition between endogenous and exogenous pools was minimized by its very small pool size and rapid metabolism. PMID:10364396

Anaerobic oxidation of toluene, phenol, and p-cresol by the dissimilatory iron-reducing organism, GS-15

USGS Publications Warehouse

Lovley, D.R.; Lonergan, D.J.

1990-01-01

The dissimilatory Fe(III) reducer, GS-15, is the first microorganism known to couple the oxidation of aromatic compounds to the reduction of Fe(III) and the first example of a pure culture of any kind known to anaerobically oxidize an aromatic hydrocarbon, toluene. In this study, the metabolism of toluene, phenol, and p-cresol by GS-15 was investigated in more detail. GS-15 grew in an anaerobic medium with toluene as the sole electron donor and Fe(III) oxide as the electron acceptor. Growth coincided with Fe(III) reduction. [ring-14C]toluene was oxidized to 14CO2, and the stoichiometry of 14CO2 production and Fe(III) reduction indicated that GS-15 completely oxidized toluene to carbon dioxide with Fe(III) as the electron acceptor. Magnetite was the primary iron end product during toluene oxidation. Phenol and p-cresol were also completely oxidized to carbon dioxide with Fe(III) as the sole electron acceptor, and GS-15 could obtain energy to support growth by oxidizing either of these compounds as the sole electron donor. p-Hydroxybenzoate was a transitory extracellular intermediate of phenol and p-cresol metabolism but not of toluene metabolism. GS-15 oxidized potential aromatic intermediates in the oxidation of toluene (benzylalcohol and benzaldehyde) and p-cresol (p-hydroxybenzylalcohol and p-hydroxybenzaldehyde). The metabolism described here provides a model for how aromatic hydrocarbons and phenols may be oxidized with the reduction of Fe(III) in contaminated aquifers and petroleum-containing sediments.

Non-statistical 13C Fractionation Distinguishes Co-incident and Divergent Steps in the Biosynthesis of the Alkaloids Nicotine and Tropine.

PubMed

Romek, Katarzyna M; Remaud, Gérald S; Silvestre, Virginie; Paneth, Piotr; Robins, Richard J

2016-08-05

During the biosynthesis of natural products, isotopic fractionation occurs due to the selectivity of enzymes for the heavier or lighter isotopomers. As only some of the positions in the molecule are implicated in a given reaction mechanism, position-specific fractionation occurs, leading to a non-statistical distribution of isotopes. This can be accessed by isotope ratio monitoring (13)C NMR spectrometry. The solanaceous alkaloids S-(-)-nicotine and hyoscyamine (atropine) are related in having a common intermediate, but downstream enzymatic steps diverge, providing a relevant test case to: (a) elucidate the isotopic affiliation between carbon atoms in the alkaloids and those in the precursors; (b) obtain information about the kinetic isotope effects of as yet undescribed enzymes, thus to make predictions as to their possible mechanism(s). We show that the position-specific (13)C/(12)C ratios in the different moieties of these compounds can satisfactorily be related to their known precursors and to the known kinetic isotope effects of enzymes involved in their biosynthesis, or to similar reaction mechanisms. Thus, the pathway to the common intermediate, N-methyl-Δ(1)-pyrrolinium, is seen to introduce similar isotope distribution patterns in the two alkaloids independent of plant species, whereas the remaining atoms of each target compound, which are of different origins, reflect their specific metabolic ancestry. We further demonstrate that the measured (13)C distribution pattern can be used to deduce aspects of the reaction mechanism of enzymes still to be identified. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Non-statistical 13C Fractionation Distinguishes Co-incident and Divergent Steps in the Biosynthesis of the Alkaloids Nicotine and Tropine*

PubMed Central

Romek, Katarzyna M.; Remaud, Gérald S.; Silvestre, Virginie; Paneth, Piotr; Robins, Richard J.

2016-01-01

During the biosynthesis of natural products, isotopic fractionation occurs due to the selectivity of enzymes for the heavier or lighter isotopomers. As only some of the positions in the molecule are implicated in a given reaction mechanism, position-specific fractionation occurs, leading to a non-statistical distribution of isotopes. This can be accessed by isotope ratio monitoring 13C NMR spectrometry. The solanaceous alkaloids S-(−)-nicotine and hyoscyamine (atropine) are related in having a common intermediate, but downstream enzymatic steps diverge, providing a relevant test case to: (a) elucidate the isotopic affiliation between carbon atoms in the alkaloids and those in the precursors; (b) obtain information about the kinetic isotope effects of as yet undescribed enzymes, thus to make predictions as to their possible mechanism(s). We show that the position-specific 13C/12C ratios in the different moieties of these compounds can satisfactorily be related to their known precursors and to the known kinetic isotope effects of enzymes involved in their biosynthesis, or to similar reaction mechanisms. Thus, the pathway to the common intermediate, N-methyl-Δ1-pyrrolinium, is seen to introduce similar isotope distribution patterns in the two alkaloids independent of plant species, whereas the remaining atoms of each target compound, which are of different origins, reflect their specific metabolic ancestry. We further demonstrate that the measured 13C distribution pattern can be used to deduce aspects of the reaction mechanism of enzymes still to be identified. PMID:27288405

Division of the intermediate compartment at the onset of mitosis provides a mechanism for Golgi inheritance.

PubMed

Marie, Michaël; Dale, Hege A; Kouprina, Nina; Saraste, Jaakko

2012-11-15

As mammalian cells prepare for mitosis, the Golgi ribbon is first unlinked into its constituent stacks and then transformed into spindle-associated, pleiomorphic membrane clusters in a process that remains enigmatic. Also, it remains unclear whether Golgi inheritance involves the incorporation of Golgi enzymes into a pool of coat protein I (COPI) vesicles, or their COPI-independent transfer to the endoplasmic reticulum (ER). Based on the observation that the intermediate compartment (IC) at the ER-Golgi boundary is connected to the centrosome, we examined its mitotic fate and possible role in Golgi breakdown. The use of multiple imaging techniques and markers revealed that the IC elements persist during the M phase, maintain their compositional and structural properties and remain associated with the mitotic spindle, forming circular arrays at the spindle poles. At G2/M transition, the movement of the pericentrosomal domain of the IC (pcIC) to the cell centre and its expansion coincide with the unlinking of the Golgi ribbon. At prophase, coupled to centrosome separation, the pcIC divides together with recycling endosomes, providing novel landmarks for mitotic entry. We provide evidence that the permanent IC elements function as way stations during the COPI-dependent dispersal of Golgi components at prometa- and metaphase, indicating that they correspond to the previously described Golgi clusters. In addition, they continue to communicate with the vesicular 'Golgi haze' and thus are likely to provide templates for Golgi reassembly. These results implicate the IC in mitotic Golgi inheritance, resulting in a model that integrates key features of the two previously proposed pathways.

Comparisons of Rain Estimates from Ground Radar and Satellite Over Mountainous Regions

NASA Technical Reports Server (NTRS)

Lin, Xin; Kidd, Chris; Tao, Jing; Barros, Ana

2016-01-01

A high-resolution rainfall product merging surface radar and an enhanced gauge network is used as a reference to examine two operational surface radar rainfall products over mountain areas. The two operational rainfall products include radar-only and conventional-gauge-corrected radar rainfall products. Statistics of rain occurrence and rain amount including their geographical, seasonal, and diurnal variations are examined using 3-year data. It is found that the three surface radar rainfall products in general agree well with one another over mountainous regions in terms of horizontal mean distributions of rain occurrence and rain amount. Frequency of rain occurrence and fraction of rain amount also indicate similar distribution patterns as a function of rain intensity. The diurnal signals of precipitation over mountain ridges are well captured and joint distributions of coincident raining samples indicate reasonable correlations during both summer and winter. Factors including undetected low-level precipitation, limited availability of gauges for correcting the Z-R relationship over the mountains, and radar beam blocking by mountains are clearly noticed in the two conventional radar rainfall products. Both radar-only and conventional-gauge-corrected radar rainfall products underestimate the rain occurrence and fraction of rain amount at intermediate and heavy rain intensities. Comparison of PR and TMI against a surface radar-only rainfall product indicates that the PR performs equally well with the high-resolution radar-only rainfall product over complex terrains at intermediate and heavy rain intensities during the summer and winter. TMI, on the other hand, requires improvement to retrieve wintertime precipitation over mountain areas.

The Adenovirus E1A C Terminus Suppresses a Delayed Antiviral Response and Modulates RAS Signaling.

PubMed

Zemke, Nathan R; Berk, Arnold J

2017-12-13

The N-terminal half of adenovirus e1a assembles multimeric complexes with host proteins that repress innate immune responses and force host cells into S-phase. In contrast, the functions of e1a's C-terminal interactions with FOXK, DCAF7, and CtBP are unknown. We found that these interactions modulate RAS signaling, and that a single e1a molecule must bind all three of these host proteins to suppress activation of a subset of IFN-stimulated genes (ISGs). These ISGs were otherwise induced in primary respiratory epithelial cells at 12 hr p.i. This delayed activation of ISGs required IRF3 and coincided with an ∼10-fold increase in IRF3 from protein stabilization. The induced IRF3 bound to chromatin and localized to the promoters of activated ISGs. While IRF3, STAT1/2, and IRF9 all greatly increased in concentration, there were no corresponding mRNA increases, suggesting that e1a regulates the stabilities of these key activators of innate immune responses, as shown directly for IRF3. Copyright © 2017 Elsevier Inc. All rights reserved.

Role of Biomass Burning in the Formation of Tropospheric Ozone Laminae

NASA Astrophysics Data System (ADS)

Nair, U. S.; Wu, Y.; Kuang, S.; Newchurch, M.

2016-12-01

Laminar structure in free-tropospheric ozone profiles is a feature that is frequently observed in ozonesonde and lidar observations. Origins of these features are not well understood and have been linked to tropopause folding, stratospheric warming events and biomass burning emissions. Ozone laminae events with maximum ozone exceeding 80 ppb have been observed by the DIfferential Absorption Lidar (DIAL) instrument in Huntsville, Alabama. While many of the events are linked to tropopause folding, a subset of events located in the mid troposphere (2-6km) coincided with a smoke layer are associated with biomass burning. Satellite observations show the smoke originated from northwestern US wildfire events. Several of these ozone laminae associated with smoke have ozone excess of 20 ppb above the background values and have the potential to impact surface air quality if they enter the boundary layer. This presentation will report on process studies of ozone laminae associated with biomass burning plumes using A-Train satellite, ground based DIAL and ozonesonde observations. Fate and transport of the feature is also examined using WRFChem simulations, in specific transport into the boundary layer and impact on air quality at the surface.

Continental-Scale Validation of Modis-Based and LEDAPS Landsat ETM + Atmospheric Correction Methods

NASA Technical Reports Server (NTRS)

Ju, Junchang; Roy, David P.; Vermote, Eric; Masek, Jeffrey; Kovalskyy, Valeriy

2012-01-01

The potential of Landsat data processing to provide systematic continental scale products has been demonstratedby several projects including the NASA Web-enabled Landsat Data (WELD) project. The recent freeavailability of Landsat data increases the need for robust and efficient atmospheric correction algorithms applicableto large volume Landsat data sets. This paper compares the accuracy of two Landsat atmospheric correctionmethods: a MODIS-based method and the Landsat Ecosystem Disturbance Adaptive ProcessingSystem (LEDAPS) method. Both methods are based on the 6SV radiative transfer code but have different atmosphericcharacterization approaches. The MODIS-based method uses the MODIS Terra derived dynamicaerosol type, aerosol optical thickness, and water vapor to atmospherically correct ETM+ acquisitions ineach coincident orbit. The LEDAPS method uses aerosol characterizations derived independently from eachLandsat acquisition and assumes a fixed continental aerosol type and uses ancillary water vapor. Validationresults are presented comparing ETM+ atmospherically corrected data generated using these two methodswith AERONET corrected ETM+ data for 95 10 km10 km 30 m subsets, a total of nearly 8 million 30 mpixels, located across the conterminous United States. The results indicate that the MODIS-based methodhas better accuracy than the LEDAPS method for the ETM+ red and longer wavelength bands.

QTL mapping for benzoxazinoid content, preharvest sprouting, α-amylase activity, and leaf rust resistance in rye (Secale cereale L.)

PubMed Central

Masojć, Piotr; Krajewski, Paweł; Stochmal, Anna; Kowalczyk, Mariusz; Angelov, Mihail; Ivanova, Valentina; Schollenberger, Małgorzata; Wakuliński, Wojciech; Banaszak, Zofia; Banaszak, Katarzyna; Rakoczy-Trojanowska, Monika

2017-01-01

Mapping population of recombinant inbred lines (RILs) representing 541 × Ot1-3 cross exhibited wide variations of benzoxazinoid (BX) content in leaves and roots, brown rust resistance, α-amylase activity in the grain, and resistance to preharvest sprouting. QTL mapping of major BX species using a DArT-based map revealed a complex genetic architecture underlying the production of these main secondary metabolites engaged in stress and allelopathy responses. The synthesis of BX in leaves and roots was found to be regulated by different QTL. The QTL for the BX content, rust resistance, α-amylase activity, and preharvest sprouting partially overlapped; this points to their common genetic regulation by a definite subset of genes. Only one QTL for BX located on chromosome 7R coincided with the loci of the ScBx genes, which were mapped as two clusters on chromosomes 5RS (Bx3-Bx5) and 7R (Bx1-Bx2). The QTL common for several BX species, rust resistance, preharvest sprouting, and α-amylase activity are interesting objects for further exploration aimed at developing common markers for these important agronomic traits. PMID:29267335

Cytokinetic Failure-induced Tetraploidy Develops into Aneuploidy, Triggering Skin Aging in Phosphovimentin-deficient Mice.

PubMed

Tanaka, Hiroki; Goto, Hidemasa; Inoko, Akihito; Makihara, Hiroyuki; Enomoto, Atsushi; Horimoto, Katsuhisa; Matsuyama, Makoto; Kurita, Kenichi; Izawa, Ichiro; Inagaki, Masaki

2015-05-22

Tetraploidy, a state in which cells have doubled chromosomal sets, is observed in ∼20% of solid tumors and is considered to frequently precede aneuploidy in carcinogenesis. Tetraploidy is also detected during terminal differentiation and represents a hallmark of aging. Most tetraploid cultured cells are arrested by p53 stabilization. However, the fate of tetraploid cells in vivo remains largely unknown. Here, we analyze the ability to repair wounds in the skin of phosphovimentin-deficient (VIM(SA/SA)) mice. Early into wound healing, subcutaneous fibroblasts failed to undergo cytokinesis, resulting in binucleate tetraploidy. Accordingly, the mRNA level of p21 (a p53-responsive gene) was elevated in a VIM(SA/SA)-specific manner. Disappearance of tetraploidy coincided with an increase in aneuploidy. Thereafter, senescence-related markers were significantly elevated in VIM(SA/SA) mice. Because our tetraploidy-prone mouse model also exhibited subcutaneous fat loss at the age of 14 months, another premature aging phenotype, our data suggest that following cytokinetic failure, a subset of tetraploid cells enters a new cell cycle and develops into aneuploid cells in vivo, which promote premature aging. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Short- and long-term memory in Drosophila require cAMP signaling in distinct neuron types.

PubMed

Blum, Allison L; Li, Wanhe; Cressy, Mike; Dubnau, Josh

2009-08-25

A common feature of memory and its underlying synaptic plasticity is that each can be dissected into short-lived forms involving modification or trafficking of existing proteins and long-term forms that require new gene expression. An underlying assumption of this cellular view of memory consolidation is that these different mechanisms occur within a single neuron. At the neuroanatomical level, however, different temporal stages of memory can engage distinct neural circuits, a notion that has not been conceptually integrated with the cellular view. Here, we investigated this issue in the context of aversive Pavlovian olfactory memory in Drosophila. Previous studies have demonstrated a central role for cAMP signaling in the mushroom body (MB). The Ca(2+)-responsive adenylyl cyclase RUTABAGA is believed to be a coincidence detector in gamma neurons, one of the three principle classes of MB Kenyon cells. We were able to separately restore short-term or long-term memory to a rutabaga mutant with expression of rutabaga in different subsets of MB neurons. Our findings suggest a model in which the learning experience initiates two parallel associations: a short-lived trace in MB gamma neurons, and a long-lived trace in alpha/beta neurons.

The arsenic exposure hypothesis for Alzheimer disease.

PubMed

Gong, Gordon; OʼBryant, Sid E

2010-01-01

Prior research has shown that arsenic exposure induces changes that coincide with most of the developmental, biochemical, pathologic, and clinical features of Alzheimer disease (AD) and associated disorders. On the basis of this literature, we propose the Arsenic Exposure Hypothesis for AD that is inclusive of and cooperative with the existing hypotheses. Arsenic toxicity induces hyperphosphorylation of protein tau and overtranscription of the amyloid precursor protein, which are involved in the formation of neurofibrillary tangles and brain amyloid plaques, consistent with the amyloid hypothesis of AD. Arsenic exposure has been associated with cardiovascular diseases and associated risk factors, which is in agreement with the vascular hypothesis of AD. Arsenic exposure invokes brain inflammatory responses, which resonates with the inflammatory hypotheses of AD. Arsenic exposure has been linked to reduced memory and intellectual abilities in children and adolescents, which provides a biologic basis for the developmental origin of health and disease hypothesis for AD. Arsenic and its metabolites generate free radicals causing oxidative stress and neuronal death, which fits the existing oxidative stress hypothesis. Taken together, the arsenic exposure hypothesis for AD provides a parsimonious testable hypothesis for the development and progression of this devastating disease at least for some subsets of individuals.

Measurement of the low energy spectral contribution in coincidence with valence band (VB) energy levels of Ag(100) using VB-VB coincidence spectroscopy

NASA Astrophysics Data System (ADS)

Gladen, R. W.; Joglekar, P. V.; Lim, Z. H.; Shastry, K.; Hulbert, S. L.; Weiss, A. H.

A set of coincidence measurements were obtained for the study and measurement of the electron contribution arising from the inter-valence band (VB) transitions along with the inelastically scattered VB electron contribution. These Auger-unrelated contributions arise in the Auger spectrum (Ag 4p NVV) obtained using Auger Photoelectron Coincidence Spectroscopy (APECS). The measured Auger-unrelated contribution can be eliminated from Auger spectrum to obtain the spectrum related to Auger. In our VB-VB coincidence measurement, a photon beam of energy 180eV was used to probe the Ag(100) sample. The coincidence spectrum was obtained using two Cylindrical Mirror Analyzers (CMA's). The scan CMA measured the low energy electron contribution in the energy range 0-70eV in coincidence with VB electrons measured by the fixed CMA. In this talk, we present the data obtained for VB-VB coincidence at the valence band energy of 171eV along with the coincidence measurements in the energy range of 4p core and valence band. NSF DMR 0907679, NSF Award Number: 1213727. Use of the National Synchrotron Light Source, Brookhaven National Laboratory, was supported by the U.S. DOE, Office of Science, Office of Basic Energy Sciences, under Contract No. DEAC02-98CH10886.

Measurement of the low energy spectral contribution in coincidence with valence band (VB) energy levels of Ag(100) using VB-VB coincidence spectroscopy

NASA Astrophysics Data System (ADS)

Joglekar, P. V.; Gladen, R.; Lim, Z. H.; Shastry, K.; Hulbert, S. L.; Weiss, A. H.

2015-03-01

A set of coincidence measurements were obtained for the study and measurement of the electron contribution arising from the inter-valence band (VB) transitions along with the inelastically scattered VB electron contribution. These Auger-unrelated contributions arise in the Auger spectrum (Ag 4p NVV) obtained using Auger Photoelectron Coincidence Spectroscopy (APECS). The measured Auger-unrelated contribution can be eliminated from Auger spectrum to obtain the spectrum related to Auger. In our VB-VB coincidence measurement, a photon beam of energy 180eV was used to probe the Ag(100) sample. The coincidence spectrum was obtained using two Cylindrical Mirror Analyzers (CMA's). The scan CMA measured the low energy electron contribution in the energy range 0-70eV in coincidence with VB electrons measured by the fixed CMA. In this talk, we present the data obtained for VB-VB coincidence at the valence band energy of 171eV along with the coincidence measurements in the energy range of 4p core and valence band. NSF DMR 0907679, NSF Award Number: 1213727. Use of the National Synchrotron Light Source, Brookhaven National Laboratory, was supported by the U.S. DOE, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-98CH10886.

Visualization and Sequencing of Membrane Remodeling Leading to Influenza Virus Fusion

PubMed Central

Gui, Long; Ebner, Jamie L.; Mileant, Alexander; Williams, James A.

2016-01-01

ABSTRACT Protein-mediated membrane fusion is an essential step in many fundamental biological events, including enveloped virus infection. The nature of protein and membrane intermediates and the sequence of membrane remodeling during these essential processes remain poorly understood. Here we used cryo-electron tomography (cryo-ET) to image the interplay between influenza virus and vesicles with a range of lipid compositions. By following the population kinetics of membrane fusion intermediates imaged by cryo-ET, we found that membrane remodeling commenced with the hemagglutinin fusion protein spikes grappling onto the target membrane, followed by localized target membrane dimpling as local clusters of hemagglutinin started to undergo conformational refolding. The local dimples then transitioned to extended, tightly apposed contact zones where the two proximal membrane leaflets were in most cases indistinguishable from each other, suggesting significant dehydration and possible intermingling of the lipid head groups. Increasing the content of fusion-enhancing cholesterol or bis-monoacylglycerophosphate in the target membrane led to an increase in extended contact zone formation. Interestingly, hemifused intermediates were found to be extremely rare in the influenza virus fusion system studied here, most likely reflecting the instability of this state and its rapid conversion to postfusion complexes, which increased in population over time. By tracking the populations of fusion complexes over time, the architecture and sequence of membrane reorganization leading to efficient enveloped virus fusion were thus resolved. IMPORTANCE Enveloped viruses employ specialized surface proteins to mediate fusion of cellular and viral membranes that results in the formation of pores through which the viral genetic material is delivered to the cell. For influenza virus, the trimeric hemagglutinin (HA) glycoprotein spike mediates host cell attachment and membrane fusion. While structures of a subset of conformations and parts of the fusion machinery have been characterized, the nature and sequence of membrane deformations during fusion have largely eluded characterization. Building upon studies that focused on early stages of HA-mediated membrane remodeling, here cryo-electron tomography (cryo-ET) was used to image the three-dimensional organization of intact influenza virions at different stages of fusion with liposomes, leading all the way to completion of the fusion reaction. By monitoring the evolution of fusion intermediate populations over the course of acid-induced fusion, we identified the progression of membrane reorganization that leads to efficient fusion by an enveloped virus. PMID:27226364

Recovery and normalization of triple coincidences in PET.

PubMed

Lage, Eduardo; Parot, Vicente; Moore, Stephen C; Sitek, Arkadiusz; Udías, Jose M; Dave, Shivang R; Park, Mi-Ae; Vaquero, Juan J; Herraiz, Joaquin L

2015-03-01

Triple coincidences in positron emission tomography (PET) are events in which three γ-rays are detected simultaneously. These events, though potentially useful for enhancing the sensitivity of PET scanners, are discarded or processed without special consideration in current systems, because there is not a clear criterion for assigning them to a unique line-of-response (LOR). Methods proposed for recovering such events usually rely on the use of highly specialized detection systems, hampering general adoption, and/or are based on Compton-scatter kinematics and, consequently, are limited in accuracy by the energy resolution of standard PET detectors. In this work, the authors propose a simple and general solution for recovering triple coincidences, which does not require specialized detectors or additional energy resolution requirements. To recover triple coincidences, the authors' method distributes such events among their possible LORs using the relative proportions of double coincidences in these LORs. The authors show analytically that this assignment scheme represents the maximum-likelihood solution for the triple-coincidence distribution problem. The PET component of a preclinical PET/CT scanner was adapted to enable the acquisition and processing of triple coincidences. Since the efficiencies for detecting double and triple events were found to be different throughout the scanner field-of-view, a normalization procedure specific for triple coincidences was also developed. The effect of including triple coincidences using their method was compared against the cases of equally weighting the triples among their possible LORs and discarding all the triple events. The authors used as figures of merit for this comparison sensitivity, noise-equivalent count (NEC) rates and image quality calculated as described in the NEMA NU-4 protocol for the assessment of preclinical PET scanners. The addition of triple-coincidence events with the authors' method increased peak NEC rates of the scanner by 26.6% and 32% for mouse- and rat-sized objects, respectively. This increase in NEC-rate performance was also reflected in the image-quality metrics. Images reconstructed using double and triple coincidences recovered using their method had better signal-to-noise ratio than those obtained using only double coincidences, while preserving spatial resolution and contrast. Distribution of triple coincidences using an equal-weighting scheme increased apparent system sensitivity but degraded image quality. The performance boost provided by the inclusion of triple coincidences using their method allowed to reduce the acquisition time of standard imaging procedures by up to ∼25%. Recovering triple coincidences with the proposed method can effectively increase the sensitivity of current clinical and preclinical PET systems without compromising other parameters like spatial resolution or contrast.

Top-of-the-Atmosphere Shortwave Flux Estimation from UV Observations: An Empirical Approach

NASA Technical Reports Server (NTRS)

Gupta, P.; Joiner, Joanna; Vasilkov, A.; Bhartia, P. K.; da Silva, Arlindo

2012-01-01

Measurements of top of the atmosphere (TOA) radiation are essential to the understanding of Earth's climate. Clouds, aerosols, and ozone (0,) are among the most important agents impacting the Earth's short-wave (SW) radiation budget. There are several sensors in orbit that provide independent information related to the Earth's SW radiation budget. Having coincident information from these sensors is important for understanding their potential contributions. The A-train constellation of satellites provides a unique opportunity to analyze near-simultaneous data from several of these sensors. They include the Ozone Monitoring Instrument (OMI), on the NASA Aura satellite, that makes TOA hyper-spectral measurements from ultraviolet (UV) to visible wavelengths, and Clouds and the Earth's Radiant Energy System (CERES) instrument, on the NASA Aqua satellite, that makes broadband measurements in both the long- and short-wave. OMI measurements have been successfully utilized to derive the information on trace gases (e.g., 0 1, NO" and SO,), clouds, and absorbing aerosols. TOA SW fluxes are estimated using a combination of data from CERES and the Aqua MODerate-resolution Imaging Spectroradiometer (MODIS). In this paper, OMI retrievals of cloud/aerosol parameters and 0 1 have been collocated with CERES TOA SW flux retrievals. We use this collocated data to develop a neural network that estimates TOA shortwave flux globally over ocean using data from OMI and meteorological analyses. This input data include the effective cloud fraction, cloud optical centroid pressure (OCP), total-column 0" and sun-satellite viewing geometry from OMI as well as wind speed and water vapor from the Goddard Earth Observing System 5 Modern Era Retrospective-analysis for Research and Applications (GEOS-5 MERRA) along with a climatology of chlorophyll content. We train the neural network using a subset of CERES retrievals of TOA SW flux as the target output (truth) and withhold a different subset of the CERES data to be used for validation.

The ancient Egyptian civilization: maximum and minimum in coincidence with solar activity

NASA Astrophysics Data System (ADS)

Shaltout, M.

It is proved from the last 22 years observations of the total solar irradiance (TSI) from space by artificial satellites, that TSI shows negative correlation with the solar activity (sunspots, flares, and 10.7cm Radio emissions) from day to day, but shows positive correlations with the same activity from year to year (on the base of the annual average for each of them). Also, the solar constant, which estimated fromth ground stations for beam solar radiations observations during the 20 century indicate coincidence with the phases of the 11- year cycles. It is known from sunspot observations (250 years) , and from C14 analysis, that there are another long-term cycles for the solar activity larger than 11-year cycle. The variability of the total solar irradiance affecting on the climate, and the Nile flooding, where there is a periodicities in the Nile flooding similar to that of solar activity, from the analysis of about 1300 years of the Nile level observations atth Cairo. The secular variations of the Nile levels, regularly measured from the 7 toth 15 century A.D., clearly correlate with the solar variations, which suggests evidence for solar influence on the climatic changes in the East African tropics The civilization of the ancient Egyptian was highly correlated with the Nile flooding , where the river Nile was and still yet, the source of the life in the Valley and Delta inside high dry desert area. The study depends on long -time historical data for Carbon 14 (more than five thousands years), and chronical scanning for all the elements of the ancient Egyptian civilization starting from the firs t dynasty to the twenty six dynasty. The result shows coincidence between the ancient Egyptian civilization and solar activity. For example, the period of pyramids building, which is one of the Brilliant periods, is corresponding to maximum solar activity, where the periods of occupation of Egypt by Foreign Peoples corresponding to minimum solar activity. The decline of the Kingdoms in ancient Egypt and occurrence of the intermediate periods are generally explained by very low Nile floods and prolonged droughts followed by severe famines and the destruction of the political structure. The study declear the role of solar activity on the climatic change, and the humankind history.

A Chandra observation of the interacting pair of galaxies NGC 4485/4490

NASA Astrophysics Data System (ADS)

Roberts, T. P.; Warwick, R. S.; Ward, M. J.; Murray, S. S.

2002-12-01

We report the results of a 20-ks Chandra ACIS-S observation of the galaxy pair NGC 4485/4490. This is an interacting system containing a late-type spiral with an enhanced star formation rate (NGC 4490), and an irregular companion that possesses a disturbed morphology. A total of 29 discrete X-ray sources are found coincident with NGC 4490, but only one is found within NGC 4485. The sources range in observed X-ray luminosity from ~2 × 1037 to 4 × 1039 erg s-1. The more luminous sources appear, on average, to be spectrally harder than the fainter sources, an effect that is attributable to increased absorption in their spectra. Extensive diffuse X-ray emission is detected coincident with the disc of NGC 4490, and in the tidal tail of NGC 4485, which appears to be thermal in nature and hence the signature of a hot interstellar medium in both galaxies. However, the diffuse component accounts for only ~10 per cent of the total X-ray luminosity of the system (2 × 1040 erg s-1, 0.5-8 keV), which arises predominantly in a handful of the brightest discrete sources. This diffuse emission fraction is unusually low for a galaxy pair which has many characteristics that would lead it to be classified as a starburst system, possibly as a consequence of the small gravitational potential well of the system. The discrete source population, on the other hand, is similar to that observed in other starburst systems, possessing a flat luminosity function slope of ~-0.6 and a total of six ultraluminous X-ray sources (ULX). Five of the ULX are identified as probable black hole X-ray binary systems, and the sixth (which is coincident with a radio continuum source) is identified as an X-ray luminous supernova remnant. The ULX all lie in star formation regions, providing further evidence of the link between the ULX phenomenon and active star formation. Importantly, this shows that even in star-forming regions, the ULX population is dominated by accreting systems. We discuss the implications of this work for physical models of the nature of ULX, and in particular how it argues against the intermediate-mass black hole hypothesis.

Hydrology of Polk County, Florida

USGS Publications Warehouse

Spechler, Rick M.; Kroening, Sharon E.

2007-01-01

Local water managers usually rely on information produced at the State and regional scale to make water-resource management decisions. Current assessments of hydrologic and water-quality conditions in Polk County, Florida, commonly end at the boundaries of two water management districts (South Florida Water Management District and the Southwest Florida Water Management District), which makes it difficult for managers to determine conditions throughout the county. The last comprehensive water-resources assessment of Polk County was published almost 40 years ago. To address the need for current countywide information, the U.S. Geological Survey began a 3?-year study in 2002 to update information about hydrologic and water-quality conditions in Polk County and identify changes that have occurred. Ground-water use in Polk County has decreased substantially since 1965. In 1965, total ground-water withdrawals in the county were about 350 million gallons per day. In 2002, withdrawals totaled about 285 million gallons per day, of which nearly 95 percent was from the Floridan aquifer system. Water-conservation practices mainly related to the phosphate-mining industry as well as the decrease in the number of mines in operation in Polk County have reduced total water use by about 65 million gallons per day since 1965. Polk County is underlain by three principal hydrogeologic units. The uppermost water-bearing unit is the surficial aquifer system, which is unconfined and composed primarily of clastic deposits. The surficial aquifer system is underlain by the intermediate confining unit, which grades into the intermediate aquifer system and consists of up to two water-bearing zones composed of interbedded clastic and carbonate rocks. The lowermost hydrogeologic unit is the Floridan aquifer system. The Floridan aquifer system, a thick sequence of permeable limestone and dolostone, consists of the Upper Floridan aquifer, a middle semiconfining unit, a middle confining unit, and the Lower Floridan aquifer. The Upper Floridan aquifer provides most of the water required to meet demand in Polk County. Data from about 300 geophysical and geologic logs were used to construct hydrogeologic maps showing the tops and thicknesses of the aquifers and confining units within Polk County. Thickness of the surficial aquifer system ranges from several feet thick or less in the extreme northwestern part of the county and along parts of the Peace River south of Bartow to more than 200 feet along the southern part of the Lake Wales Ridge in eastern Polk County. Thickness of the intermediate aquifer system/intermediate confining unit is highly variable throughout the county because of past erosional processes and sinkhole formation. Thickness of the unit ranges from less than 25 feet in the extreme northwestern part of the county to more than 300 feet in southwestern Polk County. The altitude of the top of the Upper Floridan aquifer in the county ranges from about 50 feet above National Geodetic Vertical Datum of 1929 (NGVD 29) in the northwestern part to more than 250 feet below NGVD 29 in the southern part. Water levels in the Upper Floridan aquifer fluctuate seasonally, increasing during the wet season (June through September) and decreasing during the rest of the year. Water levels in the Upper Floridan aquifer also can change from year to year, depending on such factors as pumpage and climatic variations. In the southwestern part of the county, fluctuations in water use related to phosphate mining have had a major impact on ground-water levels. Hydrographs of selected wells in southwestern Polk County show a general decline in water levels that ended in the mid-1970s. This water-level decline coincides with an increase in water use associated with phosphate mining. A substantial increase in water levels that began in the mid-1970s coincides with a period of decreasing water use in the county. Despite reductions in water use since 1970, howev

Towards component-based validation of GATE: aspects of the coincidence processor

PubMed Central

Moraes, Eder R.; Poon, Jonathan K.; Balakrishnan, Karthikayan; Wang, Wenli; Badawi, Ramsey D.

2014-01-01

GATE is public domain software widely used for Monte Carlo simulation in emission tomography. Validations of GATE have primarily been performed on a whole-system basis, leaving the possibility that errors in one sub-system may be offset by errors in others. We assess the accuracy of the GATE PET coincidence generation sub-system in isolation, focusing on the options most closely modeling the majority of commercially available scanners. Independent coincidence generators were coded by teams at Toshiba Medical Research Unit (TMRU) and UC Davis. A model similar to the Siemens mCT scanner was created in GATE. Annihilation photons interacting with the detectors were recorded. Coincidences were generated using GATE, TMRU and UC Davis code and results compared to “ground truth” obtained from the history of the photon interactions. GATE was tested twice, once with every qualified single event opening a time window and initiating a coincidence check (the “multiple window method”), and once where a time window is opened and a coincidence check initiated only by the first single event to occur after the end of the prior time window (the “single window method”). True, scattered and random coincidences were compared. Noise equivalent count rates were also computed and compared. The TMRU and UC Davis coincidence generators agree well with ground truth. With GATE, reasonable accuracy can be obtained if the single window method option is chosen and random coincidences are estimated without use of the delayed coincidence option. However in this GATE version, other parameter combinations can result in significant errors. PMID:25240897

Coincidence and covariance data acquisition in photoelectron and -ion spectroscopy. II. Analysis and applications

NASA Astrophysics Data System (ADS)

Mikosch, Jochen; Patchkovskii, Serguei

2013-10-01

We use an analytical theory of noisy Poisson processes, developed in the preceding companion publication, to compare coincidence and covariance measurement approaches in photoelectron and -ion spectroscopy. For non-unit detection efficiencies, coincidence data acquisition (DAQ) suffers from false coincidences. The rate of false coincidences grows quadratically with the rate of elementary ionization events. To minimize false coincidences for rare event outcomes, very low event rates may hence be required. Coincidence measurements exhibit high tolerance to noise introduced by unstable experimental conditions. Covariance DAQ on the other hand is free of systematic errors as long as stable experimental conditions are maintained. In the presence of noise, all channels in a covariance measurement become correlated. Under favourable conditions, covariance DAQ may allow orders of magnitude reduction in measurement times. Finally, we use experimental data for strong-field ionization of 1,3-butadiene to illustrate how fluctuations in experimental conditions can contaminate a covariance measurement, and how such contamination can be detected.

The Selective Use of Radiation Therapy in Rectal Cancer Patients.

PubMed

Martella, Andrew; Willett, Christopher; Palta, Manisha; Czito, Brian

2018-04-11

Colorectal cancer has a high global incidence, and standard treatment employs a multimodality approach. In addition to cure, minimizing treatment-related toxicity and improving the therapeutic ratio is a common goal. The following article addresses the potential of omitting radiotherapy in select rectal cancer patients. Omission of radiotherapy in rectal cancer is analyzed in the context of historical findings, as well as more recent data describing risk stratification of stage II-III disease, surgical optimization, imaging limitations, improvement in systemic chemotherapeutic agents, and contemporary studies evaluating selective omission of radiotherapy. A subset of rectal cancer patients exists that may be considered low to intermediate risk for locoregional recurrence. With appropriate staging, surgical technique, and possibly improved systemic therapy, it may be feasible to selectively omit radiotherapy in these patients. Current imaging limitations as well as evidence of increased locoregional recurrence following radiotherapy omission lend us to continue supporting the standard treatment of approach of neoadjuvant chemoradiation therapy followed by surgical resection until additional improvements and prospective evidence can support otherwise.

Modest genetic differentiation among North American populations of Sarcocystis neurona may reflect expansion in its geographic range.

PubMed

Sundar, N; Asmundsson, I M; Thomas, N J; Samuel, M D; Dubey, J P; Rosenthal, B M

2008-03-25

Sarcocystis neurona is an important cause of neurological disease in horses (equine protozoal myeloencephalitis, EPM) and sea otters in the United States. In addition, EPM-like disease has been diagnosed in several other land and marine mammals. Opossums are its only definitive hosts. Little genetic diversity among isolates of S. neurona from different hosts has been reported. Here, we used 11 microsatellites to characterize S. neurona DNA isolated from natural infections in 22 sea otters (Enhydra lutris) from California and Washington and in 11 raccoons (Procyon lotor) and 1 striped skunk (Mephitis mephitis) from Wisconsin. By jointly analyzing these 34 isolates with 26 isolates previously reported, we determined that geographic barriers may limit S. neurona dispersal and that only a limited subset of possible parasite genotypes may have been introduced to recently established opossum populations. Moreover, our study confirms that diverse intermediate hosts share a common infection source, the opossum (Didelphis virginiana).

Radial and latitudinal gradients in the solar internal angular velocity

NASA Technical Reports Server (NTRS)

Rhodes, Edward J., Jr.; Cacciani, Alessandro; Korzennik, Sylvain G.; Tomczyk, Steven; Ulrich, Roger K.; Woodard, Martin F.

1988-01-01

The frequency splittings of intermediate-degree (3 to 170 deg) p-mode oscillations obtained from a 16-day subset of observations were analyzed. Results show evidence for both radial and latitudinal gradients in the solar internal angular velocity. From 0.6 to 0.95 solar radii, the solar internal angular velocity increases systematically from 440 to 463 nHz, corresponding to a positive radial gradient of 66 nHz/solar radius for that portion of the solar interior. Analysis also indicates that the latitudinal differential rotation gradient which is seen at the solar surface persists throughout the convection zone, although there are indications that the differential rotation might disappear entirely below the base of the convection zone. The analysis was extended to include comparisons with additional observational studies and between earlier results and the results of additional inversions of several of the observational datasets. All the comparisons reinforce conclusions regarding the existence of radial and latitudinal gradients in the internal angular velocity.

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

Lieou, Charles Ka Cheong; Daub, Eric G.; Ecke, Robert E.

Rock materials often display long-time relaxation, commonly termed aging or “slow dynamics”, after the cessation of acoustic perturbations. In this paper, we focus on unconsolidated rock materials and propose to explain such nonlinear relaxation through the Shear-Transformation-Zone (STZ) theory of granular media, adapted for small stresses and strains. The theory attributes the observed relaxation to the slow, irreversible change of positions of constituent grains, and posits that the aging process can be described in three stages: fast recovery before some characteristic time associated with the subset of local plastic events or grain rearrangements with a short time scale, log-linear recoverymore » of the elastic modulus at intermediate times, and gradual turnover to equilibrium steady-state behavior at long times. Here we demonstrate good agreement with experiments on aging in granular materials such as simulated fault gouge after an external disturbance. These results may provide insights into observed modulus recovery after strong shaking in the near surface region of earthquake zones.« less

Timing and searching millisecond pulsars in globular clusters

NASA Astrophysics Data System (ADS)

D'Amico, Nichi; Possenti, Andrea; Manchester, Dick; Johnston, Simon; Kramer, Michael; Sarkissian, John; Lyne, Andrew; Burgay, Marta; Corongiu, Alessandro; Camilo, Fernando; Bailes, Matthew

2009-10-01

Timing the dozen pulsars discovered in P303 is ensuring high quality results: (a) the peculiarities (in position or projected acceleration) of all the 5 millisecond pulsars in NGC6752 suggested the presence of non thermal dynamics in the core, perhaps due to black-holes of intermediate mass; (b) the eclipsing pulsar in NGC6397 is a stereotype for studying the late evolution of exotic binaries. We propose to continue our timing project focusing mostly on NGC6752 at 20cm (in order to measure additional parameters useful to constrain the existence of a black-hole) and NGC6397 at 10cm (for studying the eclipse region and the orbital secular evolution). We also request time for performing pilot observations for a new deeper than ever search for millisecond pulsars in a subset of suitable clusters. This revamped search (as well as the requested timing observations) will exploit the new back-ends (APSR and DFB4) now available at Parkes.

The NOTCH1-autophagy interaction: Regulating self-eating for survival.

PubMed

Sarin, Apurva; Marcel, Nimi

2017-02-01

T-cell subsets in the mammalian immune system use varied mechanisms for survival, a demand imposed by the diverse and dynamic niches that they function in. In a recent study, we showed that survival of natural T-regulatory cells (Tregs) was determined by spatially regulated NOTCH1 activity signaling leading to the activation of macroautophagy/autophagy. While this interaction was revealed in experimental conditions of limited nutrient availability in vitro, the consequences of this interaction were confirmed in the context of immune physiology. Consistently, disrupting NOTCH signaling or the autophagy cascade was deleterious to Tregs. At the molecular level, ligand-activated NOTCH1, which is enriched outside the nucleus in Tregs, was detected in complexes that included specific molecular intermediates controlling the progression of autophagy. Mitochondria were a prominent cellular target, with organelle remodeling and function dependent on NOTCH1 signaling to autophagy. It is tempting to speculate that the link between autophagy and the developmental regulator NOTCH1 identified in this work may be conserved in other biological contexts.

Discovery of a regioselectivity switch in nitrating P450s guided by molecular dynamics simulations and Markov models

NASA Astrophysics Data System (ADS)

Dodani, Sheel C.; Kiss, Gert; Cahn, Jackson K. B.; Su, Ye; Pande, Vijay S.; Arnold, Frances H.

2016-05-01

The dynamic motions of protein structural elements, particularly flexible loops, are intimately linked with diverse aspects of enzyme catalysis. Engineering of these loop regions can alter protein stability, substrate binding and even dramatically impact enzyme function. When these flexible regions are unresolvable structurally, computational reconstruction in combination with large-scale molecular dynamics simulations can be used to guide the engineering strategy. Here we present a collaborative approach that consists of both experiment and computation and led to the discovery of a single mutation in the F/G loop of the nitrating cytochrome P450 TxtE that simultaneously controls loop dynamics and completely shifts the enzyme's regioselectivity from the C4 to the C5 position of L-tryptophan. Furthermore, we find that this loop mutation is naturally present in a subset of homologous nitrating P450s and confirm that these uncharacterized enzymes exclusively produce 5-nitro-L-tryptophan, a previously unknown biosynthetic intermediate.

Slow dynamics and strength recovery in unconsolidated granular earth materials: a mechanistic theory

DOE PAGES

Lieou, Charles Ka Cheong; Daub, Eric G.; Ecke, Robert E.; ...

2017-09-08

Rock materials often display long-time relaxation, commonly termed aging or “slow dynamics”, after the cessation of acoustic perturbations. In this paper, we focus on unconsolidated rock materials and propose to explain such nonlinear relaxation through the Shear-Transformation-Zone (STZ) theory of granular media, adapted for small stresses and strains. The theory attributes the observed relaxation to the slow, irreversible change of positions of constituent grains, and posits that the aging process can be described in three stages: fast recovery before some characteristic time associated with the subset of local plastic events or grain rearrangements with a short time scale, log-linear recoverymore » of the elastic modulus at intermediate times, and gradual turnover to equilibrium steady-state behavior at long times. Here we demonstrate good agreement with experiments on aging in granular materials such as simulated fault gouge after an external disturbance. These results may provide insights into observed modulus recovery after strong shaking in the near surface region of earthquake zones.« less

Modest genetic differentiation among North American populations of Sarcocystic neurona may reflect expansion in its geographic range

USGS Publications Warehouse

Sundar, N.; Asmundsson, I.M.; Thomas, N.J.; Samuel, M.D.; Dubey, J.P.; Rosenthal, B.M.

2008-01-01

Sarcocystis neurona is an important cause of neurological disease in horses (equine protozoal myeloencephalitis, EPM) and sea otters in the United States. In addition, EPM-like disease has been diagnosed in several other land and marine mammals. Opossums are its only definitive hosts. Little genetic diversity among isolates of S. neurona from different hosts has been reported. Here, we used 11 microsatellites to characterize S. neurona DNA isolated from natural infections in 22 sea otters (Enhydra lutris) from California and Washington and in 11 raccoons (Procyon lotor) and 1 striped skunk (Mephitis mephitis) from Wisconsin. By jointly analyzing these 34 isolates with 26 isolates previously reported, we determined that geographic barriers may limit S. neurona dispersal and that only a limited subset of possible parasite genotypes may have been introduced to recently established opossum populations. Moreover, our study confirms that diverse intermediate hosts share a common infection source, the opossum (Didelphis virginiana).

Slow Dynamics and Strength Recovery in Unconsolidated Granular Earth Materials: A Mechanistic Theory

NASA Astrophysics Data System (ADS)

Lieou, Charles K. C.; Daub, Eric G.; Ecke, Robert E.; Johnson, Paul A.

2017-10-01

Rock materials often display long-time relaxation, commonly termed aging or "slow dynamics," after the cessation of acoustic perturbations. In this paper, we focus on unconsolidated rock materials and propose to explain such nonlinear relaxation through the shear-transformation-zone theory of granular media, adapted for small stresses and strains. The theory attributes the observed relaxation to the slow, irreversible change of positions of constituent grains and posits that the aging process can be described in three stages: fast recovery before some characteristic time associated with the subset of local plastic events or grain rearrangements with a short time scale, log linear recovery of the elastic modulus at intermediate times, and gradual turnover to equilibrium steady state behavior at long times. We demonstrate good agreement with experiments on aging in granular materials such as simulated fault gouge after an external disturbance. These results may provide insights into observed modulus recovery after strong shaking in the near surface region of earthquake zones.

CD27 natural killer cell subsets play different roles during the pre-onset stage of experimental autoimmune encephalomyelitis.

PubMed

Gao, Ming; Yang, Yan; Li, Daling; Ming, Bingxia; Chen, Huoying; Sun, Yan; Xiao, Yifan; Lai, Lin; Zou, Huijuan; Xu, Yong; Xiong, Ping; Tan, Zheng; Gong, Feili; Zheng, Fang

2016-08-01

NK cells participate in the development of human multiple sclerosis (MS) and mouse experimental autoimmune encephalomyelitis (EAE), but the roles of different NK cell subsets in disease onset remain poorly understood. In this study, murine NK cells were divided into CD27(high) and CD27(low/-) subsets. The CD27(high) subset was decreased and the CD27(low/-) subset was increased in lymphoid organs during the pre-onset stage of EAE. Compared with the counterpart in naïve mice, the CD27(high) subset showed lower expression of Ly49D, Ly49H and NKG2D, and less production of IFN-γ, whereas the CD27(low/-) subset showed similar expression of the above mentioned surface receptors but higher cytotoxic activity in EAE mice. Compared with the CD27(high) subset, the CD27(low/-) subset exhibited increased promotion of DC maturation and no significant inhibition of T cells proliferation and Th17 cells differentiation in vitro Additionally, adoptive transfer of the CD27(low/-) subset, but not the CD27(high) subset, exacerbated the severity of EAE. Collectively, our data suggest the CD27 NK cell subsets play different roles in controlling EAE onset, which provide a new understanding for the regulation of NK cell subsets in early autoimmune disease. © The Author(s) 2016.

Recovery and normalization of triple coincidences in PET

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

Lage, Eduardo, E-mail: elage@mit.edu; Parot, Vicente; Dave, Shivang R.

2015-03-15

Purpose: Triple coincidences in positron emission tomography (PET) are events in which three γ-rays are detected simultaneously. These events, though potentially useful for enhancing the sensitivity of PET scanners, are discarded or processed without special consideration in current systems, because there is not a clear criterion for assigning them to a unique line-of-response (LOR). Methods proposed for recovering such events usually rely on the use of highly specialized detection systems, hampering general adoption, and/or are based on Compton-scatter kinematics and, consequently, are limited in accuracy by the energy resolution of standard PET detectors. In this work, the authors propose amore » simple and general solution for recovering triple coincidences, which does not require specialized detectors or additional energy resolution requirements. Methods: To recover triple coincidences, the authors’ method distributes such events among their possible LORs using the relative proportions of double coincidences in these LORs. The authors show analytically that this assignment scheme represents the maximum-likelihood solution for the triple-coincidence distribution problem. The PET component of a preclinical PET/CT scanner was adapted to enable the acquisition and processing of triple coincidences. Since the efficiencies for detecting double and triple events were found to be different throughout the scanner field-of-view, a normalization procedure specific for triple coincidences was also developed. The effect of including triple coincidences using their method was compared against the cases of equally weighting the triples among their possible LORs and discarding all the triple events. The authors used as figures of merit for this comparison sensitivity, noise-equivalent count (NEC) rates and image quality calculated as described in the NEMA NU-4 protocol for the assessment of preclinical PET scanners. Results: The addition of triple-coincidence events with the authors’ method increased peak NEC rates of the scanner by 26.6% and 32% for mouse- and rat-sized objects, respectively. This increase in NEC-rate performance was also reflected in the image-quality metrics. Images reconstructed using double and triple coincidences recovered using their method had better signal-to-noise ratio than those obtained using only double coincidences, while preserving spatial resolution and contrast. Distribution of triple coincidences using an equal-weighting scheme increased apparent system sensitivity but degraded image quality. The performance boost provided by the inclusion of triple coincidences using their method allowed to reduce the acquisition time of standard imaging procedures by up to ∼25%. Conclusions: Recovering triple coincidences with the proposed method can effectively increase the sensitivity of current clinical and preclinical PET systems without compromising other parameters like spatial resolution or contrast.« less

A systems biology approach to the analysis of subset-specific responses to lipopolysaccharide in dendritic cells.

PubMed

Hancock, David G; Shklovskaya, Elena; Guy, Thomas V; Falsafi, Reza; Fjell, Chris D; Ritchie, William; Hancock, Robert E W; Fazekas de St Groth, Barbara

2014-01-01

Dendritic cells (DCs) are critical for regulating CD4 and CD8 T cell immunity, controlling Th1, Th2, and Th17 commitment, generating inducible Tregs, and mediating tolerance. It is believed that distinct DC subsets have evolved to control these different immune outcomes. However, how DC subsets mount different responses to inflammatory and/or tolerogenic signals in order to accomplish their divergent functions remains unclear. Lipopolysaccharide (LPS) provides an excellent model for investigating responses in closely related splenic DC subsets, as all subsets express the LPS receptor TLR4 and respond to LPS in vitro. However, previous studies of the LPS-induced DC transcriptome have been performed only on mixed DC populations. Moreover, comparisons of the in vivo response of two closely related DC subsets to LPS stimulation have not been reported in the literature to date. We compared the transcriptomes of murine splenic CD8 and CD11b DC subsets after in vivo LPS stimulation, using RNA-Seq and systems biology approaches. We identified subset-specific gene signatures, which included multiple functional immune mediators unique to each subset. To explain the observed subset-specific differences, we used a network analysis approach. While both DC subsets used a conserved set of transcription factors and major signalling pathways, the subsets showed differential regulation of sets of genes that 'fine-tune' the network Hubs expressed in common. We propose a model in which signalling through common pathway components is 'fine-tuned' by transcriptional control of subset-specific modulators, thus allowing for distinct functional outcomes in closely related DC subsets. We extend this analysis to comparable datasets from the literature and confirm that our model can account for cell subset-specific responses to LPS stimulation in multiple subpopulations in mouse and man.

Response of Submerged Macrophyte Communities to External and Internal Restoration Measures in North Temperate Shallow Lakes.

PubMed

Hilt, Sabine; Alirangues Nuñez, Marta M; Bakker, Elisabeth S; Blindow, Irmgard; Davidson, Thomas A; Gillefalk, Mikael; Hansson, Lars-Anders; Janse, Jan H; Janssen, Annette B G; Jeppesen, Erik; Kabus, Timm; Kelly, Andrea; Köhler, Jan; Lauridsen, Torben L; Mooij, Wolf M; Noordhuis, Ruurd; Phillips, Geoff; Rücker, Jacqueline; Schuster, Hans-Heinrich; Søndergaard, Martin; Teurlincx, Sven; van de Weyer, Klaus; van Donk, Ellen; Waterstraat, Arno; Willby, Nigel; Sayer, Carl D

2018-01-01

Submerged macrophytes play a key role in north temperate shallow lakes by stabilizing clear-water conditions. Eutrophication has resulted in macrophyte loss and shifts to turbid conditions in many lakes. Considerable efforts have been devoted to shallow lake restoration in many countries, but long-term success depends on a stable recovery of submerged macrophytes. However, recovery patterns vary widely and remain to be fully understood. We hypothesize that reduced external nutrient loading leads to an intermediate recovery state with clear spring and turbid summer conditions similar to the pattern described for eutrophication. In contrast, lake internal restoration measures can result in transient clear-water conditions both in spring and summer and reversals to turbid conditions. Furthermore, we hypothesize that these contrasting restoration measures result in different macrophyte species composition, with added implications for seasonal dynamics due to differences in plant traits. To test these hypotheses, we analyzed data on water quality and submerged macrophytes from 49 north temperate shallow lakes that were in a turbid state and subjected to restoration measures. To study the dynamics of macrophytes during nutrient load reduction, we adapted the ecosystem model PCLake. Our survey and model simulations revealed the existence of an intermediate recovery state upon reduced external nutrient loading, characterized by spring clear-water phases and turbid summers, whereas internal lake restoration measures often resulted in clear-water conditions in spring and summer with returns to turbid conditions after some years. External and internal lake restoration measures resulted in different macrophyte communities. The intermediate recovery state following reduced nutrient loading is characterized by a few macrophyte species (mainly pondweeds) that can resist wave action allowing survival in shallow areas, germinate early in spring, have energy-rich vegetative propagules facilitating rapid initial growth and that can complete their life cycle by early summer. Later in the growing season these plants are, according to our simulations, outcompeted by periphyton, leading to late-summer phytoplankton blooms. Internal lake restoration measures often coincide with a rapid but transient colonization by hornworts, waterweeds or charophytes. Stable clear-water conditions and a diverse macrophyte flora only occurred decades after external nutrient load reduction or when measures were combined.

State dynamics of a double sandbar system

NASA Astrophysics Data System (ADS)

Price, T. D.; Ruessink, B. G.

2011-04-01

A 9.3-year dataset of low-tide time-exposure images from Surfers Paradise, Northern Gold Coast, Australia was used to characterise the state dynamics of a double sandbar system. The morphology of the nearshore sandbars was described by means of the sequential bar state classification scheme of Wright and Short [1984. Morphodynamic variability of surf zones and beaches: a synthesis. Marine Geology 56, 93-118]. Besides the two end members (the dissipative (D) and the reflective (R) states) and the four intermediate states (longshore bar and trough (LBT), rhythmic bar and beach (RBB), transverse bar and rip (TBR) and low tide terrace (LTT)), we identified two additional intermediate bar states. The erosive transverse bar and rip (eTBR) state related to the dominant oblique angle of wave incidence at the study site and the rhythmic low tide terrace (rLTT) related to the multiple bar setting. Using the alongshore barline variability and alongshore trough continuity as morphological indicators enabled the objective classification of the inner and outer bar states from the images. The outer bar was mostly in the TBR state and generally advanced sequentially through the states LBT-RBB-TBR-eTBR-LBT, with occasional transitions to the D state. Wave events led to abrupt state transitions of the outer bar, but, in contrast to expectations, did not necessarily correspond to upstate transitions. Instead, upstate (downstate) transitions coincided with angles of wave incidence θ larger (smaller) than 30°. The upstate TBR-eTBR-LBT sequence during high-angle events highlights the role of alongshore currents in bar straightening. The outer bar was found to govern the state of the inner bar to a large extent. Two types of inner bar behaviour were distinguished, based on the outer bar state. For intermediate outer bar states, the alongshore variability of the dominant inner rLTT state (52% in time) mainly related to that of the outer bar, implying some sort of morphological coupling. For dissipative outer bar states, however, the more upstate inner bar frequently separated from the shoreline and persistently developed rip channels as TBR became the most frequent state (60% in time).

Thermal and Denaturation Studies of the Time-Resolved Fluorescence Decay of Human Superoxide Dismutase

NASA Astrophysics Data System (ADS)

Silva, Norberto De Jesus

Previous studies have shown that time-resolved fluorescence decay of various single tryptophan proteins is best described by a distribution of fluorescence lifetimes rather than one or two lifetimes. The thermal dependence of the lifetime distributions is consistent with the hypothesis that proteins fluctuate between a hierarchy of many conformational substates. With this scenario as a theoretical framework, the correlations between protein dynamic and structure are investigated by studying the time-resolved fluorescence and anisotropy decay of the single tryptophan (Trp) residue of human superoxide dismutase (HSOD) over a wide range of temperatures and at different denaturant concentrations. First, it is demonstrated that the center of the lifetime distribution can characterize the average deactivation environment of the excited Trp-protein system. A qualitative model is introduced to explain the time-resolved fluorescence decay of HSOD in 80% glycerol over a wide range of temperatures. The dynamical model features isoenergetic conformational substates separated by a hierarchy of energy barriers. The HSOD system is also investigated as a function of denaturant concentration in aqueous solution. As a function of guanidine hydrochloride (GdHCl), the width of the fluorescence lifetime distribution of HSOD displays a maximum which is not coincident with the fully denatured form of HSOD at 6.5M GdHCl. Furthermore, the width for the fully denatured form of HSOD is greater than that of the native form. This is consistent with the scenario that more conformational substates are being created upon denaturation of HSOD. HSOD is a dimeric protein and it was observed that the width of the lifetime distribution of HSOD at intermediate GdHCl concentrations increased with decreasing protein concentration. In addition, the secondary structure of HSOD at intermediate GdHCl concentration does not change with protein concentration. These results suggest that HSOD display structural microheterogeneity which is consistent with the hypothesis of conformational substates. Further analysis show that, during denaturation, the monomeric form of HSOD is an intermediate which displays native-like secondary structure and fluctuating tertiary structure; i.e., the monomeric form of HSOD is a molten globule.

CO2 and circulation in the deglacial North Pacific

NASA Astrophysics Data System (ADS)

Taylor, B.; Rae, J. W. B.; Gray, W. R.; Rees-Owen, R. L.; Burke, A.

2017-12-01

The North Pacific is the largest carbon reservoir in the global ocean, but has not typically been thought to play an active role in deglacial CO2 rise based on its modern stratified state. Recent studies (Okazaki et al., 2010; Rae et al., 2014; Max et al., 2017), however, have suggested that a more dynamic circulation regime operated in the glacial and deglacial North Pacific and, as such, the role of the North Pacific in deglacial CO2 rise may have been underestimated. We present two new high-resolution boron isotope records of surface water pCO2 from the North West and North East Pacific spanning the last 22 kyrs. The two records show remarkable coherence over key intervals during the last deglaciation and highlight major changes over a number of abrupt climate events. At both sites, following the LGM, pCO2(sw) rises, coincident with a younging of North Pacific intermediate and deep waters. This suggests that increased local overturning mixed CO2-rich deep waters throughout the water column, likely contributing to CO2 outgassing during Heinrich Stadial 1 (HS1). Both records exhibit decreases in pCO2(sw) during the latter stages of HS1, which are immediately followed by a rapid increase in pCO2(sw) at the onset of the Bølling-Allerød (B/A). Radiocarbon and δ13C data indicate a collapse in North Pacific Intermediate Water formation at the onset of the B/A, which, combined with enhanced wind stress curl, would have allowed CO2-rich waters to mix into the surface ocean from intermediate-depths. The combination of high nutrient availability and a seasonally well-stratified mixed layer likely led to the abrupt increase in export productivity across the region; the excess surface water CO2 shows that alleviation of iron or light limitation could not have been its primary cause. Our new records highlight the importance of overturning circulation in the North Pacific in controlling productivity and CO2 release on glacial/interglacial timescales.

Roles for Coincidence Detection in Coding Amplitude-Modulated Sounds

PubMed Central

Ashida, Go; Kretzberg, Jutta; Tollin, Daniel J.

2016-01-01

Many sensory neurons encode temporal information by detecting coincident arrivals of synaptic inputs. In the mammalian auditory brainstem, binaural neurons of the medial superior olive (MSO) are known to act as coincidence detectors, whereas in the lateral superior olive (LSO) roles of coincidence detection have remained unclear. LSO neurons receive excitatory and inhibitory inputs driven by ipsilateral and contralateral acoustic stimuli, respectively, and vary their output spike rates according to interaural level differences. In addition, LSO neurons are also sensitive to binaural phase differences of low-frequency tones and envelopes of amplitude-modulated (AM) sounds. Previous physiological recordings in vivo found considerable variations in monaural AM-tuning across neurons. To investigate the underlying mechanisms of the observed temporal tuning properties of LSO and their sources of variability, we used a simple coincidence counting model and examined how specific parameters of coincidence detection affect monaural and binaural AM coding. Spike rates and phase-locking of evoked excitatory and spontaneous inhibitory inputs had only minor effects on LSO output to monaural AM inputs. In contrast, the coincidence threshold of the model neuron affected both the overall spike rates and the half-peak positions of the AM-tuning curve, whereas the width of the coincidence window merely influenced the output spike rates. The duration of the refractory period affected only the low-frequency portion of the monaural AM-tuning curve. Unlike monaural AM coding, temporal factors, such as the coincidence window and the effective duration of inhibition, played a major role in determining the trough positions of simulated binaural phase-response curves. In addition, empirically-observed level-dependence of binaural phase-coding was reproduced in the framework of our minimalistic coincidence counting model. These modeling results suggest that coincidence detection of excitatory and inhibitory synaptic inputs is essential for LSO neurons to encode both monaural and binaural AM sounds. PMID:27322612

Coincidence detection in the medial superior olive: mechanistic implications of an analysis of input spiking patterns

PubMed Central

Franken, Tom P.; Bremen, Peter; Joris, Philip X.

2014-01-01

Coincidence detection by binaural neurons in the medial superior olive underlies sensitivity to interaural time difference (ITD) and interaural correlation (ρ). It is unclear whether this process is akin to a counting of individual coinciding spikes, or rather to a correlation of membrane potential waveforms resulting from converging inputs from each side. We analyzed spike trains of axons of the cat trapezoid body (TB) and auditory nerve (AN) in a binaural coincidence scheme. ITD was studied by delaying “ipsi-” vs. “contralateral” inputs; ρ was studied by using responses to different noises. We varied the number of inputs; the monaural and binaural threshold and the coincidence window duration. We examined physiological plausibility of output “spike trains” by comparing their rate and tuning to ITD and ρ to those of binaural cells. We found that multiple inputs are required to obtain a plausible output spike rate. In contrast to previous suggestions, monaural threshold almost invariably needed to exceed binaural threshold. Elevation of the binaural threshold to values larger than 2 spikes caused a drastic decrease in rate for a short coincidence window. Longer coincidence windows allowed a lower number of inputs and higher binaural thresholds, but decreased the depth of modulation. Compared to AN fibers, TB fibers allowed higher output spike rates for a low number of inputs, but also generated more monaural coincidences. We conclude that, within the parameter space explored, the temporal patterns of monaural fibers require convergence of multiple inputs to achieve physiological binaural spike rates; that monaural coincidences have to be suppressed relative to binaural ones; and that the neuron has to be sensitive to single binaural coincidences of spikes, for a number of excitatory inputs per side of 10 or less. These findings suggest that the fundamental operation in the mammalian binaural circuit is coincidence counting of single binaural input spikes. PMID:24822037

What do correlations tell us about anthropogenic-biogenic interactions and SOA formation in the Sacramento Plume during CARES?

NASA Astrophysics Data System (ADS)

Kleinman, L.; Kuang, C.; Sedlacek, A.; Senum, G.; Springston, S.; Wang, J.; Zhang, Q.; Jayne, J.; Fast, J.; Hubbe, J.; Shilling, J.; Zaveri, R.

2015-09-01

During the Carbonaceous Aerosols and Radiative Effects Study (CARES) the DOE G-1 aircraft was used to sample aerosol and gas phase compounds in the Sacramento, CA plume and surrounding region. We present data from 66 plume transects obtained during 13 flights in which southwesterly winds transported the plume towards the foothills of the Sierra Nevada Mountains. Plume transport occurred partly over land with high isoprene emission rates. Our objective is to empirically determine whether organic aerosol (OA) can be attributed to anthropogenic or biogenic sources, and to determine whether there is a synergistic effect whereby OA concentrations are enhanced by the simultaneous presence of high concentrations of CO and either isoprene, MVK+MACR (sum of methyl vinyl ketone and methacrolein) or methanol, which are taken as tracers of anthropogenic and biogenic emissions, respectively. Linear and bilinear correlations between OA, CO, and each of three biogenic tracers, "Bio", for individual plume transects indicate that most of the variance in OA over short time and distance scales can be explained by CO. For each transect and species a plume perturbation, (i.e., ΔOA, defined as the difference between 90th and 10th percentiles) was defined and regressions done amongst Δ values in order to probe day to day and location dependent variability. Species that predicted the largest fraction of the variance in ΔOA were ΔO3 and ΔCO. Background OA was highly correlated with background methanol and poorly correlated with other tracers. Because background OA was ~ 60 % of peak OA in the urban plume, peak OA should be primarily biogenic and therefore non-fossil. Transects were split into subsets according to the percentile rankings of ΔCO and ΔBio, similar to an approach used by Setyan et al. (2012) and Shilling et al. (2013) to determine if anthropogenic-biogenic interactions enhance OA production. As found earlier, ΔOA in the data subset having high ΔCO and high ΔBio was several-fold greater than in other subsets. Part of this difference is consistent with a synergistic interaction between anthropogenic and biogenic precursors and part to an independent linear dependence of ΔOA on precursors. Highest values of ΔO3 also occur in the high ΔCO-high ΔBio data set, raising the possibility that the coincidence of high concentrations of anthropogenic and biogenic tracers as well as OA and O3 may be associated with high temperatures, clear skies, and poor ventilation in addition to specific interaction between anthropogenic and biogenic compounds.

Towards component-based validation of GATE: aspects of the coincidence processor.

PubMed

Moraes, Eder R; Poon, Jonathan K; Balakrishnan, Karthikayan; Wang, Wenli; Badawi, Ramsey D

2015-02-01

GATE is public domain software widely used for Monte Carlo simulation in emission tomography. Validations of GATE have primarily been performed on a whole-system basis, leaving the possibility that errors in one sub-system may be offset by errors in others. We assess the accuracy of the GATE PET coincidence generation sub-system in isolation, focusing on the options most closely modeling the majority of commercially available scanners. Independent coincidence generators were coded by teams at Toshiba Medical Research Unit (TMRU) and UC Davis. A model similar to the Siemens mCT scanner was created in GATE. Annihilation photons interacting with the detectors were recorded. Coincidences were generated using GATE, TMRU and UC Davis code and results compared to "ground truth" obtained from the history of the photon interactions. GATE was tested twice, once with every qualified single event opening a time window and initiating a coincidence check (the "multiple window method"), and once where a time window is opened and a coincidence check initiated only by the first single event to occur after the end of the prior time window (the "single window method"). True, scattered and random coincidences were compared. Noise equivalent count rates were also computed and compared. The TMRU and UC Davis coincidence generators agree well with ground truth. With GATE, reasonable accuracy can be obtained if the single window method option is chosen and random coincidences are estimated without use of the delayed coincidence option. However in this GATE version, other parameter combinations can result in significant errors. Copyright © 2014 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Sensitivity to coincidences and paranormal belief.

PubMed

Hadlaczky, Gergö; Westerlund, Joakim

2011-12-01

Often it is difficult to find a natural explanation as to why a surprising coincidence occurs. In attempting to find one, people may be inclined to accept paranormal explanations. The objective of this study was to investigate whether people with a lower threshold for being surprised by coincidences have a greater propensity to become believers compared to those with a higher threshold. Participants were exposed to artificial coincidences, which were formally defined as less or more probable, and were asked to provide remarkability ratings. Paranormal belief was measured by the Australian Sheep-Goat Scale. An analysis of the remarkability ratings revealed a significant interaction effect between Sheep-Goat score and type of coincidence, suggesting that people with lower thresholds of surprise, when experiencing coincidences, harbor higher paranormal belief than those with a higher threshold. The theoretical aspects of these findings were discussed.

It takes two-coincidence coding within the dual olfactory pathway of the honeybee.

PubMed

Brill, Martin F; Meyer, Anneke; Rössler, Wolfgang

2015-01-01

To rapidly process biologically relevant stimuli, sensory systems have developed a broad variety of coding mechanisms like parallel processing and coincidence detection. Parallel processing (e.g., in the visual system), increases both computational capacity and processing speed by simultaneously coding different aspects of the same stimulus. Coincidence detection is an efficient way to integrate information from different sources. Coincidence has been shown to promote associative learning and memory or stimulus feature detection (e.g., in auditory delay lines). Within the dual olfactory pathway of the honeybee both of these mechanisms might be implemented by uniglomerular projection neurons (PNs) that transfer information from the primary olfactory centers, the antennal lobe (AL), to a multimodal integration center, the mushroom body (MB). PNs from anatomically distinct tracts respond to the same stimulus space, but have different physiological properties, characteristics that are prerequisites for parallel processing of different stimulus aspects. However, the PN pathways also display mirror-imaged like anatomical trajectories that resemble neuronal coincidence detectors as known from auditory delay lines. To investigate temporal processing of olfactory information, we recorded PN odor responses simultaneously from both tracts and measured coincident activity of PNs within and between tracts. Our results show that coincidence levels are different within each of the two tracts. Coincidence also occurs between tracts, but to a minor extent compared to coincidence within tracts. Taken together our findings support the relevance of spike timing in coding of olfactory information (temporal code).

Functional heterogeneity of human effector CD8+ T cells.

PubMed

Takata, Hiroshi; Naruto, Takuya; Takiguchi, Masafumi

2012-02-09

Effector CD8(+) T cells are believed to be terminally differentiated cells having cytotoxic activity and the ability to produce effector cytokines such as INF-γ and TNF-α. We investigated the difference between CXCR1(+) and CXCR1(-) subsets of human effector CD27(-)CD28(-)CD8(+) T cells. The subsets expressed cytolytic molecules similarly and exerted substantial cytolytic activity, whereas only the CXCR1(-) subset had IL-2 productivity and self-proliferative activity and was more resistant to cell death than the CXCR1(+) subset. These differences were explained by the specific up-regulation of CAMK4, SPRY2, and IL-7R in the CXCR1(-) subset and that of pro-apoptotic death-associated protein kinase 1 (DAPK1) in the CXCR1(+) subset. The IL-2 producers were more frequently found in the IL-7R(+) subset of the CXCR1(-) effector CD8(+) T cells than in the IL-7R(-) subset. IL-7/IL-7R signaling promoted cell survival only in the CXCR1(-) subset. The present study has highlighted a novel subset of effector CD8(+) T cells producing IL-2 and suggests the importance of this subset in the homeostasis of effector CD8(+) T cells.

Quantifying radionuclide signatures from a γ-γ coincidence system.

PubMed

Britton, Richard; Jackson, Mark J; Davies, Ashley V

2015-11-01

A method for quantifying gamma coincidence signatures has been developed, and tested in conjunction with a high-efficiency multi-detector system to quickly identify trace amounts of radioactive material. The γ-γ system utilises fully digital electronics and list-mode acquisition to time-stamp each event, allowing coincidence matrices to be easily produced alongside typical 'singles' spectra. To quantify the coincidence signatures a software package has been developed to calculate efficiency and cascade summing corrected branching ratios. This utilises ENSDF records as an input, and can be fully automated, allowing the user to quickly and easily create/update a coincidence library that contains all possible γ and conversion electron cascades, associated cascade emission probabilities, and true-coincidence summing corrected γ cascade detection probabilities. It is also fully searchable by energy, nuclide, coincidence pair, γ multiplicity, cascade probability and half-life of the cascade. The probabilities calculated were tested using measurements performed on the γ-γ system, and found to provide accurate results for the nuclides investigated. Given the flexibility of the method, (it only relies on evaluated nuclear data, and accurate efficiency characterisations), the software can now be utilised for a variety of systems, quickly and easily calculating coincidence signature probabilities. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Anthropic Reasoning about Fine-Tuning, and Neoclassical Cosmology: Providence, Omnipresence, and Observation Selection Theory

NASA Astrophysics Data System (ADS)

Walker, Theodore, Jr.

2011-10-01

Anthropic reasoning about observation selection effects upon the appearance of cosmic providential fine-tuning (fine-tuning that provides for life) is often motivated by a desire to avoid theological implications (implications favoring the idea of a divine cosmic provider) without appealing to sheer lucky-for-us-cosmic-jackpot happenstance and coincidence. Cosmic coincidence can be rendered less incredible by appealing to a multiverse context. Cosmic providence can be rendered non-theological by appealing to an agent-less providential purpose, or by appealing to less-than-omnipresent/local providers, such as alien intelligences creating life- providing baby universes. Instead of choosing either cosmic coincidence or cosmic providence, as though they were mutually exclusive; it is better to accept both. Neoclassical thought accepts coincidence and providence, plus many local providers and one omnipresent provider. Moreover, fundamental observation selection theory should distinguish the many local observers of some events from the one omnipresent observer of all events. Accepting both coincidence and providence avoids classical theology (providence without coincidence) and classical atheism (coincidence without providence), but not neoclassical theology (providence with coincidence). Cosmology cannot avoid the idea of an all-inclusive omnipresent providential dice-throwing living-creative whole of reality, an idea essential to neoclassical theology, and to neoclassical cosmology.

Tight bounds for the Pearle-Braunstein-Caves chained inequality without the fair-coincidence assumption

NASA Astrophysics Data System (ADS)

Jogenfors, Jonathan; Larsson, Jan-Åke

2017-08-01

In any Bell test, loopholes can cause issues in the interpretation of the results, since an apparent violation of the inequality may not correspond to a violation of local realism. An important example is the coincidence-time loophole that arises when detector settings might influence the time when detection will occur. This effect can be observed in many experiments where measurement outcomes are to be compared between remote stations because the interpretation of an ostensible Bell violation strongly depends on the method used to decide coincidence. The coincidence-time loophole has previously been studied for the Clauser-Horne-Shimony-Holt and Clauser-Horne inequalities, but recent experiments have shown the need for a generalization. Here, we study the generalized "chained" inequality by Pearle, Braunstein, and Caves (PBC) with N ≥2 settings per observer. This inequality has applications in, for instance, quantum key distribution where it has been used to reestablish security. In this paper we give the minimum coincidence probability for the PBC inequality for all N ≥2 and show that this bound is tight for a violation free of the fair-coincidence assumption. Thus, if an experiment has a coincidence probability exceeding the critical value derived here, the coincidence-time loophole is eliminated.

The hydrography of the Mozambique Channel from six years of continuous temperature, salinity, and velocity observations

NASA Astrophysics Data System (ADS)

Ullgren, J. E.; van Aken, H. M.; Ridderinkhof, H.; de Ruijter, W. P. M.

2012-11-01

Temperature, salinity and velocity data are presented, along with the estimated volume transport, from seven full-length deep sea moorings placed across the narrowest part of the Mozambique Channel, southwest Indian Ocean, during the period November 2003 to December 2009. The dominant water mass in the upper layer is Sub-Tropical Surface Water (STSW) which overlies South Indian Central Water (SICW), and is normally capped by fresher Tropical Surface Water (TSW). Upper ocean salinity increased through 2005 as a result of saline STSW taking up a relatively larger part of the upper layer, at the expense of TSW. Upper waters are on average warmer and lighter in the central Channel than on the sides. Throughout the upper 1.5 km of the water column there is large hydrographic variability, short-term as well as interannual, and in particular at frequencies (four to seven cycles per year) associated with the southward passage of anticyclonic Mozambique Channel eddies. The eddies have a strong T-S signal, in the upper and central waters as well as on the intermediate level, as the eddies usually carry saline Red Sea Water (RSW) in their core. While the interannual frequency band displays an east-west gradient with higher temperature variance on the western side, the eddy frequency band shows highest variance in the centre of the Channel, where the eddy band contains about 40% of the total isopycnal hydrographic variability. Throughout the >6 years of measurements, the frequency and characteristics of eddies vary between periods, both in terms of strength and vertical structure of eddy T-S signals. These changes contribute to the interannual variability of water mass properties: an increase in central water salinity to a maximum in late 2007 coincided with a period of unusually frequent eddies with strong salinity signals. The warmest and most saline deep water is found within the northward flowing Mozambique Undercurrent, on the western side of the Channel. The Undercurrent has two cores: an intermediate one mainly containing diluted Antarctic Intermediate Water (AAIW), and a deep one consisting of North Atlantic Deep Water (NADW). In the intermediate core, T-S properties are strongly correlated with current velocity, probably because of the strong salinity gradient at the interface between Red Sea Water (RSW) and AAIW. In the deep core, velocity and hydrographic time series do not correlate on a daily basis, but they do at longer time scales.

Towards understanding the role of the Bering Strait in the Plio-Pleistocene climate change

NASA Astrophysics Data System (ADS)

Okazaki, Y.; Onodera, J.; Teraishi, A.; Suto, I.

2011-12-01

The Bering Strait is the gateway between Pacific and Arctic, plays an important role in global freshwater cycle and eventually influences on climate change. The glacial Pacific Ocean had well-ventilated and nutrient-depleted glacial North Pacific Intermediate Water (GNPIW) above ~2000 m. GNPIW is a thicker and more deeply penetrating water mass than today's North Pacific Intermediate Water (NPIW). The source of GNPIW was likely in the Bering Sea based on neodymium isotope evidence. During Heinrich Event 1 in the early deglacial period, deep water extending to a depth of ~2500 m formed in the North Pacific. Modeling simulations suggest that a closed Bering Strait is essentially required for salinity built-up in the North Pacific to form the deep water. First opening of the Bering Strait was suggested to be in the latest Miocene and have repeated opening and closure by eustatic sea-level change associated with climate changes. However, our knowledge on the history about the opening/closure is limited due to lack of appropriate samples. During the IODP Expedition 323, Pliocene to Pleistocene marine sediment was continuously recovered from the Bering Sea. At the northern Bering continental slope sites (U1343 and U1344), the period with high abundance of diatom species Neodenticula seminae is terminated around 0.8-0.9 Ma, which appears to coincide with the Mid-Pleistocene Transition (MPT). While Neodenticula seminae is an endemic and predominant diatom in the modern subarctic Pacific and the Aleutian basin of the Bering Sea, the occurrence of this species is reported from the sediments between 0.84 and 1.25 Ma in the northern North Atlantic. This suggests a significantly intensified Arctic Throughflow and adaptive environment for N. seminae production from the Bering Strait to the Greenland Sea during the MPT. The observations of hydrography and the modern re-appearance of this taxon since 1999 in the Labrador Sea due to the melting of the Arctic Sea ice also suggests the specific requirements by this species: low salinity and high dissolved silicon concentrations. During the glacial cycles of the last 800 kyr, a limited input of Pacific water into the Arctic Ocean or disconnection was suggested by decreased abundances of N. seminae. Furthermore, repeated abundance peaks of radiolarian species Cycladophora davisiana, indicating cold and well ventilated intermediate water, suggest enhancement of intermediate to deep water formation in the Bering Sea during glacial periods, when the Bering Strait was closed. This research used samples and data provided by the IODP. We acknowledge the IODP Expedition 323 Shipboard Scientists.

Target Detection Routine (TADER). User’s Guide.

DTIC Science & Technology

1987-09-01

o System range capability subset (one record - omitted for standoff SLAR and penetrating system) o System inherent detection probability subset ( IELT ...records, i.e., one per element type) * System capability modifier subset/A=1, E=1 ( IELT records) o System capability modifier subset/A=1, E=2 ( IELT ...records) s System capability modifier subset/A=2, E=1 ( IELT records) o System capability modifier subset/A=2, E=2 ( IELT records) Unit Data Set (one set

CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900

PubMed Central

Gönen, Mithat; Sun, Zhuoxin; Figueroa, Maria E.; Patel, Jay P.; Abdel-Wahab, Omar; Racevskis, Janis; Ketterling, Rhett P.; Fernandez, Hugo; Rowe, Jacob M.; Tallman, Martin S.; Melnick, Ari; Levine, Ross L.

2012-01-01

We determined the prognostic relevance of CD25 (IL-2 receptor-α) expression in 657 patients (≤ 60 years) with de novo acute myeloid leukemia (AML) treated in the Eastern Cooperative Oncology Group trial, E1900. We identified CD25POS myeloblasts in 87 patients (13%), of whom 92% had intermediate-risk cytogenetics. CD25 expression correlated with expression of stem cell antigen CD123. In multivariate analysis, controlled for prognostic baseline characteristics and daunorubicin dose, CD25POS patients had inferior complete remission rates (P = .0005) and overall survival (P < .0001) compared with CD25NEG cases. In a subset of 396 patients, we integrated CD25 expression with somatic mutation status to determine whether CD25 impacted outcome independent of prognostic mutations. CD25 was positively correlated with internal tandem duplications in FLT3 (FLT3-ITD), DNMT3A, and NPM1 mutations. The adverse prognostic impact of FLT3-ITDPOS AML was restricted to CD25POS patients. CD25 expression improved AML prognostication independent of integrated, cytogenetic and mutational data, such that it reallocated 11% of patients with intermediate-risk disease to the unfavorable-risk group. Gene expression analysis revealed that CD25POS status correlated with the expression of previously reported leukemia stem cell signatures. We conclude that CD25POS status provides prognostic relevance in AML independent of known biomarkers and is correlated with stem cell gene-expression signatures associated with adverse outcome in AML. PMID:22855599

Twenty-four-hour endocrine and metabolic profiles following consumption of high-fructose corn syrup-, sucrose-, fructose-, and glucose-sweetened beverages with meals.

PubMed

Stanhope, Kimber L; Griffen, Steven C; Bair, Brandi R; Swarbrick, Michael M; Keim, Nancy L; Havel, Peter J

2008-05-01

We have reported that, compared with glucose-sweetened beverages, consuming fructose-sweetened beverages with meals results in lower 24-h circulating glucose, insulin, and leptin concentrations and elevated triacylglycerol (TG). However, pure fructose and glucose are not commonly used as sweeteners. High-fructose corn syrup (HFCS) has replaced sucrose as the predominant sweetener in beverages in the United States. We compared the metabolic/endocrine effects of HFCS with sucrose and, in a subset of subjects, with pure fructose and glucose. Thirty-four men and women consumed 3 isocaloric meals with either sucrose- or HFCS-sweetened beverages, and blood samples were collected over 24 h. Eight of the male subjects were also studied when fructose- or glucose-sweetened beverages were consumed. In 34 subjects, 24-h glucose, insulin, leptin, ghrelin, and TG profiles were similar between days that sucrose or HFCS was consumed. Postprandial TG excursions after HFCS or sucrose were larger in men than in women. In the men in whom the effects of 4 sweeteners were compared, the 24-h glucose and insulin responses induced by HFCS and sucrose were intermediate between the lower responses during consumption of fructose and the higher responses during glucose. Unexpectedly, postprandial TG profiles after HFCS or sucrose were not intermediate but comparably high as after pure fructose. Sucrose and HFCS do not have substantially different short-term endocrine/metabolic effects. In male subjects, short-term consumption of sucrose and HFCS resulted in postprandial TG responses comparable to those induced by fructose.

Twenty-four Hour Endocrine and Metabolic Profiles Following Consumption of High Fructose Corn Syrup-, Sucrose- Fructose-, and Glucose-Sweetened Beverages with Meals

PubMed Central

Stanhope, Kimber L.; Griffen, Steven C.; Bair, Brandi R.; Swarbrick, Michael M.; Keim, Nancy L.; Havel, Peter J.

2011-01-01

Background We have reported that compared with glucose-sweetened beverages, consuming fructose-sweetened beverages with meals results in lower 24-h circulating glucose, insulin and leptin concentrations, and elevated triacylglycerol (TG). However, pure fructose and glucose are not commonly used as sweeteners. High fructose corn syrup (HFCS) has replaced sucrose as the predominant sweetener in beverages in the U.S. Objective We compared the metabolic/endocrine effects of HFCS with sucrose, and in a subset of subjects with pure fructose and glucose. Design 34 men and women consumed 3 isocaloric meals with either sucrose- or HFCS-sweetened beverages, and blood samples were collected over 24 hours. Eight of the male subjects were also studied when fructose- or glucose-sweetened beverages were consumed. Results In 34 subjects, 24-h glucose, insulin, leptin, ghrelin and TG profiles were similar between days that sucrose or HFCS were consumed. Postprandial TG excursions after HFCS or sucrose were larger in men than women. In the men in whom the effects of 4 sweeteners were compared, the 24-h glucose and insulin responses induced by HFCS and sucrose were intermediate between the lower responses during consumption of fructose and the higher responses during glucose. Unexpectedly, postprandial TG profiles after HFCS or sucrose were not intermediate, but comparably high as after pure fructose. Conclusions Sucrose and HFCS do not have substantially different short-term endocrine/metabolic effects. In male subjects, short-term consumption of sucrose and HFCS resulted in postprandial TG responses comparable to those induced by fructose. PMID:18469239

An Invasive Fish and the Time-Lagged Spread of Its Parasite across the Hawaiian Archipelago

PubMed Central

Gaither, Michelle R.; Aeby, Greta; Vignon, Matthias; Meguro, Yu-ichiro; Rigby, Mark; Runyon, Christina; Toonen, Robert J.; Wood, Chelsea L.; Bowen, Brian W.

2013-01-01

Efforts to limit the impact of invasive species are frustrated by the cryptogenic status of a large proportion of those species. Half a century ago, the state of Hawai'i introduced the Bluestripe Snapper, Lutjanus kasmira, to O'ahu for fisheries enhancement. Today, this species shares an intestinal nematode parasite, Spirocamallanus istiblenni, with native Hawaiian fishes, raising the possibility that the introduced fish carried a parasite that has since spread to naïve local hosts. Here, we employ a multidisciplinary approach, combining molecular, historical, and ecological data to confirm the alien status of S. istiblenni in Hawai'i. Using molecular sequence data we show that S. istiblenni from Hawai'i are genetically affiliated with source populations in French Polynesia, and not parasites at a geographically intermediate location in the Line Islands. S. istiblenni from Hawai'i are a genetic subset of the more diverse source populations, indicating a bottleneck at introduction. Ecological surveys indicate that the parasite has found suitable intermediate hosts in Hawai'i, which are required for the completion of its life cycle, and that the parasite is twice as prevalent in Hawaiian Bluestripe Snappers as in source populations. While the introduced snapper has spread across the entire 2600 km archipelago to Kure Atoll, the introduced parasite has spread only half that distance. However, the parasite faces no apparent impediments to invading the entire archipelago, with unknown implications for naïve indigenous Hawaiian fishes and the protected Papahānaumokuākea Marine National Monument. PMID:23468894

Role of toll-like receptor 4 Asp299Gly polymorphism in the development of cardiovascular diseases in HIV-infected patients.

PubMed

Tarancon-Diez, Laura; De Pablo-Bernal, Rebeca S; Jiménez, José L; Álvarez-Ríos, Ana I; Genebat, Miguel; Rosado-Sánchez, Isaac; Muñoz-Fernández, María-Ángeles; Ruiz-Mateos, Ezequiel; Leal, Manuel

2018-05-15

Cardiovascular diseases (CVDs) are one of the main causes of morbimortality in HIV-infected patients on suppressive antiretroviral therapy. The objective of this work was to evaluate the role of single nucleotide polymorphisms (SNPs) in lipopolysaccharide (LPS) Toll-like receptor 4 (TLR4) and CVDs occurrence in HIV-infected patients. Additionally, the functional consequences of carrying these SNPs were analyzed. The association of TLR4 SNPs, Asp299Gly/Thr399Ile with CVDs occurrence was analyzed using multivariate logistic regression models. Clinical, immunological, and traditional cardiovascular risk factors were used as covariates. The monocyte phenotype and response were assessed by multiparametric flow cytometry comparing carriers with noncarriers of this SNP. Asp299Gly SNP, assayed in 253 HIV-infected patients, was independently associated with the occurrence of CVDs after adjusting for CD4 T-cell nadir, HCV-coinfection, bacterial pneumonia, diabetes mellitus, and traditional cardiovascular risk factors [odds ratio (confidence interval 95%) = 3.672 (1.061-12.712), P = 0.04). Carriers of Asp299Gly SNP showed higher percentage of patrolling and intermediate monocytes producing a proinflammatory combination of cytokines compared with noncarriers (P = 0.037 and P = 0.046, respectively). Intermediate monocyte subset levels correlated with soluble interleukin-6 levels only in carriers (r = 0.89; P = 0.01). TLR4 Asp299Gly polymorphism is independently associated with the occurrence of CVDs in HIV-infected patients. The proinflammatory profile associated to this variant could be involved in the development of atherosclerotic pathologies.

Spectro-Timing Study of GX 339-4 in a Hard Intermediate State

NASA Technical Reports Server (NTRS)

Furst, F.; Grinberg, V.; Tomsick, J. A.; Bachetti, M.; Boggs, S. E.; Brightman, M.; Christensen, F. E.; Craig, W. W.; Ghandi, P.; Zhang, William W.

2016-01-01

We present an analysis of Nuclear Spectroscopic Telescope Array observations of a hard intermediate state of the transient black hole GX 339-4 taken in 2015 January. With the source softening significantly over the course of the 1.3 day long observation we split the data into 21 sub-sets and find that the spectrum of all of them can be well described by a power-law continuum with an additional relativistically blurred reflection component. The photon index increases from approx. 1.69 to approx. 1.77 over the course of the observation. The accretion disk is truncated at around nine gravitational radii in all spectra. We also perform timing analysis on the same 21 individual data sets, and find a strong type-C quasi-periodic oscillation (QPO), which increases in frequency from approx. 0.68 to approx. 1.05 Hz with time. The frequency change is well correlated with the softening of the spectrum. We discuss possible scenarios for the production of the QPO and calculate predicted inner radii in the relativistic precession model as well as the global disk mode oscillations model. We find discrepancies with respect to the observed values in both models unless we allow for a black hole mass of approx. 100 Mass compared to the Sun, which is highly unlikely. We discuss possible systematic uncertainties, in particular with the measurement of the inner accretion disk radius in the relativistic reflection model. We conclude that the combination of observed QPO frequencies and inner accretion disk radii, as obtained from spectral fitting, is difficult to reconcile with current models.

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: A review of human brain oscillations as effective endophenotypes

PubMed Central

Rangaswamy, Madhavi; Porjesz, Bernice

2010-01-01

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders. PMID:18634760

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: a review of human brain oscillations as effective endophenotypes.

PubMed

Rangaswamy, Madhavi; Porjesz, Bernice

2008-10-15

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders.

Gene expression profile in cerebrum in the filial imprinting of domestic chicks (Gallus gallus domesticus).

PubMed

Yamaguchi, Shinji; Fujii-Taira, Ikuko; Katagiri, Sachiko; Izawa, Ei-Ichi; Fujimoto, Yasuyuki; Takeuchi, Hideaki; Takano, Tatsuya; Matsushima, Toshiya; Homma, Koichi J

2008-06-15

In newly hatched chicks, gene expression in the brain has previously been shown to be up-regulated following filial imprinting. By applying cDNA microarrays containing 13,007 expressed sequence tags, we examined the comprehensive gene expression profiling of the intermediate medial mesopallium in the chick cerebrum, which has been shown to play a key role in filial imprinting. We found 52 up-regulated genes and 6 down-regulated genes of at least 2.0-fold changes 3h after the training of filial imprinting, compared to the gene expression of the dark-reared chick brain. The up-regulated genes are known to be involved in a variety of pathways, including signal transduction, cytoskeletal organization, nuclear function, cell metabolism, RNA binding, endoplasmic reticulum or Golgi function, synaptic function, ion channel, and transporter. In contrast, fewer genes were down-regulated in the imprinting, coinciding with the previous data that the total RNA synthesis increased associated with filial imprinting. Our data suggests that the filial imprinting involves the modulation of multiple signaling pathways.

The ultraviolet flux distribution of Alpha-2 Canum Venaticorum

NASA Technical Reports Server (NTRS)

Leckrone, D. S.; Snijders, M. A. J.

1979-01-01

Intermediate- and narrow-band UV spectrophotometry from Copernicus, OAO 2, the S2-68 experiment on TD 1, and a sounding-rocket experiment are combined with ground-based observations to define the absolute flux distribution of the bright magnetic Ap star Alpha-2 CVn over the wavelength range from 1030 to 7580 A. Two flux distributions are presented which coincide more or less with the rare-earth maximum and minimum in the star's cycle. The results are compared with those for two normal stars, the UV variability of Alpha-2 CVn is characterized as a function of wavelength, and non-LTE effects on the UV continua of C I and Si I are analyzed. Some physical properties of Alpha-2 CVn are estimated, and the evolutionary age of the star is estimated to be between 220 million and 300 million years. It is concluded that Alpha-2 CVn is old enough to have been magnetically braked to its current rotational velocity by either the centrifugal-wind or the accretion mechanism and to have developed its chemical peculiarities by either mechanism.

Chromatic Dimensions Earthy, Watery, Airy, and Fiery.

PubMed

Albertazzi, Liliana; Koenderink, Jan J; van Doorn, Andrea

2015-01-01

In our study, for a small number of antonyms, we investigate whether they are cross-modally or ideaesthetically related to the space of colors. We analyze the affinities of seven antonyms (cold-hot, dull-radiant, dead-vivid, soft-hard, transparent-chalky, dry-wet, and acid-treacly) and their intermediate connotations (cool-warm, matt-shiny, numb-lively, mellow-firm, semi-transparent-opaque, semi-dry-moist, and sour-sweet) as a function of color. We find that some antonyms relate to chromatic dimensions, others to achromatic ones. The cold-hot antonym proves to be the most salient dimension. The dry-wet dimension coincides with the cold-hot dimension, with dry corresponding to hot and wet to cold. The acid-treacly dimension proves to be transversal to the cold-hot dimension; hence, the pairs mutually span the chromatic domain. The cold-hot and acid-treacly antonyms perhaps recall Hering's opponent color system. The dull-radiant, transparent-chalky, and dead-vivid pairs depend little upon chromaticity. Of all seven antonyms, only the soft-hard one turns out to be independent of the chromatic structure. © The Author(s) 2015.

Reconciling Scratch Space Consumption, Exposure, and Volatility to Achieve Timely Staging of Job Input Data

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

Monti, Henri; Butt, Ali R; Vazhkudai, Sudharshan S

2010-04-01

Innovative scientific applications and emerging dense data sources are creating a data deluge for high-end computing systems. Processing such large input data typically involves copying (or staging) onto the supercomputer's specialized high-speed storage, scratch space, for sustained high I/O throughput. The current practice of conservatively staging data as early as possible makes the data vulnerable to storage failures, which may entail re-staging and consequently reduced job throughput. To address this, we present a timely staging framework that uses a combination of job startup time predictions, user-specified intermediate nodes, and decentralized data delivery to coincide input data staging with job start-up.more » By delaying staging to when it is necessary, the exposure to failures and its effects can be reduced. Evaluation using both PlanetLab and simulations based on three years of Jaguar (No. 1 in Top500) job logs show as much as 85.9% reduction in staging times compared to direct transfers, 75.2% reduction in wait time on scratch, and 2.4% reduction in usage/hour.« less

Theoretical constraints on masses of heavy particles in Left-Right symmetric models

NASA Astrophysics Data System (ADS)

Chakrabortty, J.; Gluza, J.; Jeliński, T.; Srivastava, T.

2016-08-01

Left-Right symmetric models with general gL ≠gR gauge couplings which include bidoublet and triplet scalar multiplets are studied. Possible scalar mass spectra are outlined by imposing Tree-Unitarity, and Vacuum Stability criteria and also using the bounds on neutral scalar masses MHFCNC which assure the absence of Flavour Changing Neutral Currents (FCNC). We are focusing on mass spectra relevant for the LHC analysis, i.e., the scalar masses are around TeV scale. As all non-standard heavy particle masses are related to the vacuum expectation value (VEV) of the right-handed triplet (vR), the combined effects of relevant Higgs potential parameters and MHFCNC regulate the lower limits of heavy gauge boson masses. The complete set of Renormalization Group Evolutions for all couplings are provided at the 1-loop level, including the mixing effects in the Yukawa sector. Most of the scalar couplings suffer from the Landau poles at the intermediate scale Q ∼106.5 GeV, which in general coincides with violation of the Tree-Unitarity bounds.

La Freccia Rossa: An IR-dark cloud hosting the Milky Way intermediate-mass black hole candidate

NASA Astrophysics Data System (ADS)

Ravi, Vikram; Vedantham, Harish; Phinney, E. Sterl

2018-05-01

The dynamics of the high-velocity compact molecular cloud CO-0.40-0.22 have been interpreted as evidence for a ˜105M⊙ black hole within 60 pc of Sgr A*. Recently, Oka et al. have identified a compact millimetre-continuum source, CO-0.40-0.22*, with this candidate black hole. Here we present a collation of radio and infrared data at this location. ATCA constraints on the radio spectrum, and the detection of a mid-infrared counterpart, are in tension with an Sgr A*-like model for CO-0.40-0.22* despite the comparable bolometric to Eddington luminosity ratios under the IMBH interpretation. A protostellar-disk scenario is, however, tenable. CO-0.40-0.22(*) is positionally coincident with an arrowhead-shaped infrared-dark cloud (which we call the Freccia Rossa). If the VLSR ≈ 70 km s-1 systemic velocity of CO-0.40-0.22 is common to the entire Freccia Rossa system, we hypothesise that it is the remnant of a high-velocity cloud that has plunged into the Milky Way from the Galactic halo.

The spectrum of wind speed fluctuations encountered by a rotating blade of a wind energy conversion system

NASA Astrophysics Data System (ADS)

Connell, J. R.

1982-01-01

The results of anemometer, hot-wire anemometer, and laser anemometer array and crosswind sampling of wind speed and turbulence in an area swept by intermediate-to-large wind turbine blades are presented, with comparisons made with a theoretical model for the wind fluctuations. A rotating frame of reference was simulated by timing the anemometric readings at different points of the actuator disk area to coincide with the moment a turbine blade would pass through the point. The hot-wire sensors were mounted on an actual rotating boom, while the laser scanned the wind velocity field in a vertical crosswind circle. The midfrequency region of the turbulence spectrum was found to be depleted, with energy shifted to the high end of the spectrum, with an additional peak at the rotation frequency of the rotor. A model is developed, assuming homogeneous, isotropic turbulence, to reproduce the observed spectra and verify and extend scaling relations using turbine and atmospheric length and time scales. The model is regarded as useful for selecting wind turbine hub heights and rotor rotation rates.

Cross-shell excitations in Si 31

DOE PAGES

Tai, P. -L.; Tabor, S. L.; Lubna, R. S.; ...

2017-07-28

The Si-31 nucleus was produced through the O-18(18O, an) fusion-evaporation reaction at E-lab = 24 MeV. Evaporated a particles from the reaction were detected and identified in the Microball detector array for channel selection. Multiple gamma-ray coincidence events were detected in Gammasphere. The energy and angle information for the alpha particles was used to determine the Si-31 recoil kinematics on an event-by-event basis for a more accurate Doppler correction. A total of 22 new states and 52 new gamma transitions were observed, including 14 from states above the neutron separation energy. The positive-parity states predicted by the shell-model calculations inmore » the sd model space agree well with experiment. The negative-parity states were compared with shell-model calculations in the psdpf model space with some variations in the N = 20 shell gap. The best agreement was found with a shell gap intermediate between that originally used for A approximate to 20 nuclei and that previously adapted for P-32,P-34. This variation suggests the need for a more universal cross-shell interaction.« less

Economy, Movement Dynamics, and Muscle Activity of Human Walking at Different Speeds.

PubMed

Raffalt, P C; Guul, M K; Nielsen, A N; Puthusserypady, S; Alkjær, T

2017-03-08

The complex behaviour of human walking with respect to movement variability, economy and muscle activity is speed dependent. It is well known that a U-shaped relationship between walking speed and economy exists. However, it is an open question if the movement dynamics of joint angles and centre of mass and muscle activation strategy also exhibit a U-shaped relationship with walking speed. We investigated the dynamics of joint angle trajectories and the centre of mass accelerations at five different speeds ranging from 20 to 180% of the predicted preferred speed (based on Froude speed) in twelve healthy males. The muscle activation strategy and walking economy were also assessed. The movement dynamics was investigated using a combination of the largest Lyapunov exponent and correlation dimension. We observed an intermediate stage of the movement dynamics of the knee joint angle and the anterior-posterior and mediolateral centre of mass accelerations which coincided with the most energy-efficient walking speed. Furthermore, the dynamics of the joint angle trajectories and the muscle activation strategy was closely linked to the functional role and biomechanical constraints of the joints.

Mechanical control of mitotic progression in single animal cells

PubMed Central

Cattin, Cedric J.; Düggelin, Marcel; Martinez-Martin, David; Gerber, Christoph; Müller, Daniel J.; Stewart, Martin P.

2015-01-01

Despite the importance of mitotic cell rounding in tissue development and cell proliferation, there remains a paucity of approaches to investigate the mechanical robustness of cell rounding. Here we introduce ion beam-sculpted microcantilevers that enable precise force-feedback–controlled confinement of single cells while characterizing their progression through mitosis. We identify three force regimes according to the cell response: small forces (∼5 nN) that accelerate mitotic progression, intermediate forces where cells resist confinement (50–100 nN), and yield forces (>100 nN) where a significant decline in cell height impinges on microtubule spindle function, thereby inhibiting mitotic progression. Yield forces are coincident with a nonlinear drop in cell height potentiated by persistent blebbing and loss of cortical F-actin homogeneity. Our results suggest that a buildup of actomyosin-dependent cortical tension and intracellular pressure precedes mechanical failure, or herniation, of the cell cortex at the yield force. Thus, we reveal how the mechanical properties of mitotic cells and their response to external forces are linked to mitotic progression under conditions of mechanical confinement. PMID:26305930

Charged Particle Identification for Prefragmentation Studies

NASA Astrophysics Data System (ADS)

Hu, Jonathan; MoNA Collaboration

2017-09-01

Projectile fragmentation refers to high energy (>50 MeV/u) heavy ion beams on production targets to generate intermediate mass and target fragments at facilities like the NSCL, FRIB, GSI, GANIL and RIKEN. The resulting secondary beams can then be isolated by fragment separators like the NCSL's A1900 and that secondary beam then used on reaction targets for a variety of experiments. Predictions of beam intensities for experiment planning depend on models and data. The MoNA Collaboration performed an experiment at the NSCL in which a 48Ca primary beam was used with a 9Be target to produce a 32Mg secondary beam with energy 86 MeV/u that was incident on a second target of 9Be. By characterizing the energy distributions of final fragments of neon, sodium, and fluorine in coincidence with neutrons created both by prefragmentation processes and reaction mechanisms, we are able to extract information about prefragmentation dynamics. The identification of charged fragments is a multi-step process crucial to this analysis. This work is supported by the National Science Foundation under Grant No. PHY-1613429.

Analysis of the yeast short-term Crabtree effect and its origin

PubMed Central

Hagman, Arne; Säll, Torbjörn; Piškur, Jure

2014-01-01

The short-term Crabtree effect is defined as the immediate occurrence of aerobic alcoholic fermentation in response to provision of a pulse of excess sugar to sugar-limited yeast cultures. Here we have characterized ten yeast species with a clearly defined phylogenetic relationship. Yeast species were cultivated under glucose-limited conditions, and we studied their general carbon metabolism in response to a glucose pulse. We generated an extensive collection of data on glucose and oxygen consumption, and ethanol and carbon dioxide generation. We conclude that the Pichia,Debaryomyces,Eremothecium and Kluyveromyces marxianus yeasts do not exhibit any significant ethanol formation, while Kluyveromyces lactis behaves as an intermediate yeast, and Lachancea,Torulaspora,Vanderwaltozyma and Saccharomyces yeasts exhibit rapid ethanol accumulation. Based on the present data and our previous data relating to the presence of the long-term Crabtree effect in over 40 yeast species, we speculate that the origin of the short-term effect may coincide with the origin of the long-term Crabtree effect in the Saccharomycetales lineage, occurring ∼ 150 million years ago. PMID:25161062

Apoptotic cell death in the central nervous system of Bufo arenarum tadpoles induced by cypermethrin.

PubMed

Casco, V H; Izaguirre, M F; Marín, L; Vergara, M N; Lajmanovich, R C; Peltzer, P; Soler, A Peralta

2006-05-01

Tadpoles of the toad Bufo arenarum treated with cypermethrin (CY) at concentrations above 39 mug CY/L showed dose-dependent apoptotic cell death in immature cells of the central nervous system as demonstrated by morphometric analysis, the TUNEL method, and DNA fragmentation assay. Light-and electron-microscopic studies showed structural alterations in the intermediate and marginal layers of the brain. Immature cerebral tissue showed cellular shrinkage, nuclear fragmentation and increase of intercellular spaces. In this study we demonstrated high toxicity of CY to larval stages of Bufo arenarum. Our results show that doses lower than those used in routine insecticide applications can cause massive apoptosis in the immature cells of the central nervous system. These results coincide with our previous studies in Physalaemus biligonigerus, confirming the severe toxic effects of CY to the central nervous system of anuran species from Argentina. This may increase the mortality index in wild animals and contribute to the loss of biodiversity in our agroecosystems. We postulate that CY induces apoptosis in central nervous system cells of Bufo arenarum tadpoles by specific neurotoxic mechanisms.

Oligocene sivaladapid primate from the Bugti Hills (Balochistan, Pakistan) bridges the gap between Eocene and Miocene adapiform communities in Southern Asia.

PubMed

Marivaux, Laurent; Welcomme, Jean-Loup; Ducrocq, Stéphane; Jaeger, Jean-Jacques

2002-04-01

A new species of Guangxilemur (Sivaladapidae, Adapiformes) is described from the early Oligocene Chitarwata Formation (Bugti Member) of the Bugti Hills, Sulaiman geological Province, Balochistan, Pakistan. Guangxilemur singsilai n. sp. provides further diagnostic morphological characters from its newly described upper and lower dentitions, confirming its intermediate phylogenetic position between Eocene and Miocene Asian sivaladapid adapiforms. G. singsilai possesses moderately developed shearing and puncturing molar features and maintains lingual cusps on upper molars as in Eocene hoanghoniines; in contrast, it possesses a typical molariform P(4) as in Miocene sivaladapines. The important paleogeographic changes that have affected South Asia during the Tertiary (related to the collision between the Indian and Eurasian Plates) have played a critical role in reforming circulation and climatic differentiation. The presence in Pakistan of an unique and well-diversified Oligocene primate fauna, clearly demonstrates that South Asia maintained favourable environmental conditions during the middle Caenozoic global climatic deterioration that coincides with drastic changes in faunal structure on the whole Holarctic Province, including the extinction of adapiform primates. Copyright 2002 Elsevier Science Ltd.

Many-Body Localization and Quantum Nonergodicity in a Model with a Single-Particle Mobility Edge.

PubMed

Li, Xiaopeng; Ganeshan, Sriram; Pixley, J H; Das Sarma, S

2015-10-30

We investigate many-body localization in the presence of a single-particle mobility edge. By considering an interacting deterministic model with an incommensurate potential in one dimension we find that the single-particle mobility edge in the noninteracting system leads to a many-body mobility edge in the corresponding interacting system for certain parameter regimes. Using exact diagonalization, we probe the mobility edge via energy resolved entanglement entropy (EE) and study the energy resolved applicability (or failure) of the eigenstate thermalization hypothesis (ETH). Our numerical results indicate that the transition separating area and volume law scaling of the EE does not coincide with the nonthermal to thermal transition. Consequently, there exists an extended nonergodic phase for an intermediate energy window where the many-body eigenstates violate the ETH while manifesting volume law EE scaling. We also establish that the model possesses an infinite temperature many-body localization transition despite the existence of a single-particle mobility edge. We propose a practical scheme to test our predictions in atomic optical lattice experiments which can directly probe the effects of the mobility edge.

Stress-gradient hypothesis explains susceptibility to Bromus tectorum invasion and community stability in North America's semi-arid Artemisia tridentata wyomingensis ecosystems

USGS Publications Warehouse

Reisner, Michael D.; Doescher, Paul S.; Pyke, David A.

2015-01-01

Results/Conclusions: Cattle herbivory, a novel disturbance and selective force, was a significant component of two overlapping stress gradients most strongly associated with observed shifts in interactions. Facilitation and competition were strongest and most frequent at the highest and lowest stress levels along both gradients, respectively. Contrasting ecological optima among native and non-native beneficiaries led to strikingly different patterns of interactions. The four native bunchgrasses with the strongest competitive response abilities exhibited the strongest facilitation at their upper limits of stress tolerance, while the two non-natives exhibited the strongest competition at the highest stress levels, which coincided with their maximum abundance. Artemisia facilitation enhanced stability at intermediate stress levels by providing a refuge for native bunchgrasses, which in turn reduced the magnitude of B. tectorum invasion. However, facilitation was a destabilizing force at the highest stress levels when native bunchgrasses became obligate beneficiaries dependent on facilitation for their persistence. B. tectorum dominated these communities, and the next fire may convert them to annual grasslands.

Spontaneous and natural cytotoxicity receptor-mediated cytotoxicity are effector functions of distinct natural killer subsets in hepatitis C virus-infected chimpanzees.

PubMed

Verstrepen, B E; Nieuwenhuis, I G; Mooij, P; Bogers, W M; Boonstra, A; Koopman, G

2016-07-01

In humans, CD16 and CD56 are used to identify functionally distinct natural killer (NK) subsets. Due to ubiquitous CD56 expression, this marker cannot be used to distinguish between NK cell subsets in chimpanzees. Therefore, functional analysis of distinct NK subsets during hepatitis C virus (HCV) infection has never been performed in these animals. In the present study an alternative strategy was used to identify four distinct NK subsets on the basis of the expression of CD16 and CD94. The expression of activating and inhibiting surface receptors showed that these subsets resemble human NK subsets. CD107 expression was used to determine degranulation of the different subsets in naive and HCV-infected chimpanzees. In HCV-infected chimpanzees increased spontaneous cytotoxicity was observed in CD94(high/dim) CD16(pos) and CD94(low) CD16(pos) subsets. By contrast, increased natural cytotoxicity receptor (NCR)- mediated degranulation after NKp30 and NKp44 triggering was demonstrated in the CD94(dim) CD16(neg) subset. Our findings suggest that spontaneous and NCR-mediated cytotoxicity are effector functions of distinct NK subsets in HCV-infected chimpanzees. © 2016 British Society for Immunology.

Aggregation of carbon dioxide sequestration storage assessment units

USGS Publications Warehouse

Blondes, Madalyn S.; Schuenemeyer, John H.; Olea, Ricardo A.; Drew, Lawrence J.

2013-01-01

The U.S. Geological Survey is currently conducting a national assessment of carbon dioxide (CO2) storage resources, mandated by the Energy Independence and Security Act of 2007. Pre-emission capture and storage of CO2 in subsurface saline formations is one potential method to reduce greenhouse gas emissions and the negative impact of global climate change. Like many large-scale resource assessments, the area under investigation is split into smaller, more manageable storage assessment units (SAUs), which must be aggregated with correctly propagated uncertainty to the basin, regional, and national scales. The aggregation methodology requires two types of data: marginal probability distributions of storage resource for each SAU, and a correlation matrix obtained by expert elicitation describing interdependencies between pairs of SAUs. Dependencies arise because geologic analogs, assessment methods, and assessors often overlap. The correlation matrix is used to induce rank correlation, using a Cholesky decomposition, among the empirical marginal distributions representing individually assessed SAUs. This manuscript presents a probabilistic aggregation method tailored to the correlations and dependencies inherent to a CO2 storage assessment. Aggregation results must be presented at the basin, regional, and national scales. A single stage approach, in which one large correlation matrix is defined and subsets are used for different scales, is compared to a multiple stage approach, in which new correlation matrices are created to aggregate intermediate results. Although the single-stage approach requires determination of significantly more correlation coefficients, it captures geologic dependencies among similar units in different basins and it is less sensitive to fluctuations in low correlation coefficients than the multiple stage approach. Thus, subsets of one single-stage correlation matrix are used to aggregate to basin, regional, and national scales.

Cessation of tyrosine kinase inhibitors in patients with chronic-phase chronic myelogenous leukemia following durable complete molecular response: a single center facing the dilemma.

PubMed

Iliakis, Theodoros; Papadopoulou, Vasiliki; Diamantopoulos, Panagiotis T; Panayiotidis, Panayiotis; Zervakis, Konstantinos; Giannakopoulou, Nefeli; Tilimidos, Gerassimos; Angelopoulou, Maria; Siakantaris, Marina P; Pangalis, Gerassimos; Mantzourani, Marina; Variami, Eleni; Viniou, Nora Athina

2013-08-01

Tyrosine kinase inhibitors (TKIs), namely imatinib mesylate (IM) and recently approved second-generation TKIs dasatinib and nilotinib, are currently considered the treatment of choice for newly-diagnosed chronic phase chronic myelogenous leukemia (CP-CML). Although treatment with TKIs has not yet been proven curative, it certainly accomplishes a sustained control of the disease in the vast majority of patients. More than a decade after the successful launching of IM in first-line treatment of CP-CML and the subsequent introduction of second-generation TKIs in this setting, the question of the possibility of TKI cessation in a specific subset of patients has emerged. Side-effects of TKIs, along with some patients' wish to abandon the drugs and the rising financial burden upon healthcare systems, have led to the dilemma whether IM can be safely withdrawn after achieving deep molecular remissions and which patients are suitable for this discontinuation. We examined the data of our patients with CML in search of potential canditates for cessation of TKI therapy and identified their characteristics. We also performed a thorough review of the relevant literature. Eight out of fifty patients were discriminated on grounds of sustained complete molecular response (CMR) exceeding 12 months, most of them with a low or intermediate Sokal score at diagnosis. The median interval from IM initiation to CMR was almost 2 years and the median duration of detected CMR reached 6.5 years. Based on the promising results of prospective clinical trials reporting successful cessation of treatment with TKIs on selected subgroups of patients, we decided to proceed to interruption of therapy in the specific subset of our patients and closely monitor their response.

Contribution to the Solar Mean Magnetic Field from Different Solar Regions

NASA Astrophysics Data System (ADS)

Kutsenko, A. S.; Abramenko, V. I.; Yurchyshyn, V. B.

2017-09-01

Seven-year-long seeing-free observations of solar magnetic fields with the Helioseismic and Magnetic Imager (HMI) on board the Solar Dynamics Observatory (SDO) were used to study the sources of the solar mean magnetic field, SMMF, defined as the net line-of-sight magnetic flux divided over the solar disk area. To evaluate the contribution of different regions to the SMMF, we separated all the pixels of each SDO/HMI magnetogram into three subsets: weak (BW), intermediate (BI), and strong (BS) fields. The BW component represents areas with magnetic flux densities below the chosen threshold; the BI component is mainly represented by network fields, remains of decayed active regions (ARs), and ephemeral regions. The BS component consists of magnetic elements in ARs. To derive the contribution of a subset to the total SMMF, the linear regression coefficients between the corresponding component and the SMMF were calculated. We found that i) when the threshold level of 30 Mx cm-2 is applied, the BI and BS components together contribute from 65% to 95% of the SMMF, while the fraction of the occupied area varies in a range of 2 - 6% of the disk area; ii) as the threshold magnitude is lowered to 6 Mx cm-2, the contribution from BI+BS grows to 98%, and the fraction of the occupied area reaches a value of about 40% of the solar disk. In summary, we found that regardless of the threshold level, only a small part of the solar disk area contributes to the SMMF. This means that the photospheric magnetic structure is an intermittent inherently porous medium, resembling a percolation cluster. These findings suggest that the long-standing concept that continuous vast unipolar areas on the solar surface are the source of the SMMF may need to be reconsidered.

Genetic hotels for the standard genetic code: evolutionary analysis based upon novel three-dimensional algebraic models.

PubMed

José, Marco V; Morgado, Eberto R; Govezensky, Tzipe

2011-07-01

Herein, we rigorously develop novel 3-dimensional algebraic models called Genetic Hotels of the Standard Genetic Code (SGC). We start by considering the primeval RNA genetic code which consists of the 16 codons of type RNY (purine-any base-pyrimidine). Using simple algebraic operations, we show how the RNA code could have evolved toward the current SGC via two different intermediate evolutionary stages called Extended RNA code type I and II. By rotations or translations of the subset RNY, we arrive at the SGC via the former (type I) or via the latter (type II), respectively. Biologically, the Extended RNA code type I, consists of all codons of the type RNY plus codons obtained by considering the RNA code but in the second (NYR type) and third (YRN type) reading frames. The Extended RNA code type II, comprises all codons of the type RNY plus codons that arise from transversions of the RNA code in the first (YNY type) and third (RNR) nucleotide bases. Since the dimensions of remarkable subsets of the Genetic Hotels are not necessarily integer numbers, we also introduce the concept of algebraic fractal dimension. A general decoding function which maps each codon to its corresponding amino acid or the stop signals is also derived. The Phenotypic Hotel of amino acids is also illustrated. The proposed evolutionary paths are discussed in terms of the existing theories of the evolution of the SGC. The adoption of 3-dimensional models of the Genetic and Phenotypic Hotels will facilitate the understanding of the biological properties of the SGC.

Evidence for a stepwise program of extrathymic T cell development within the human tonsil

PubMed Central

McClory, Susan; Hughes, Tiffany; Freud, Aharon G.; Briercheck, Edward L.; Martin, Chelsea; Trimboli, Anthony J.; Yu, Jianhua; Zhang, Xiaoli; Leone, Gustavo; Nuovo, Gerard; Caligiuri, Michael A.

2012-01-01

The development of a broad repertoire of T cells, which is essential for effective immune function, occurs in the thymus. Although some data suggest that T cell development can occur extrathymically, many researchers remain skeptical that extrathymic T cell development has an important role in generating the T cell repertoire in healthy individuals. However, it may be important in the setting of poor thymic function or congenital deficit and in the context of autoimmunity, cancer, or regenerative medicine. Here, we report evidence that a stepwise program of T cell development occurs within the human tonsil. We identified 5 tonsillar T cell developmental intermediates: (a) CD34+CD38dimLin– cells, which resemble multipotent progenitors in the bone marrow and thymus; (b) more mature CD34+CD38brightLin– cells; (c) CD34+CD1a+CD11c– cells, which resemble committed T cell lineage precursors in the thymus; (d) CD34–CD1a+CD3–CD11c– cells, which resemble CD4+CD8+ double-positive T cells in the thymus; and (e) CD34–CD1a+CD3+CD11c– cells. The phenotype of each subset closely resembled that of its thymic counterpart. The last 4 populations expressed RAG1 and PTCRA, genes required for TCR rearrangement, and all 5 subsets were capable of ex vivo T cell differentiation. TdT+ cells found within the tonsillar fibrous scaffold expressed CD34 and/or CD1a, indicating that this distinct anatomic region contributes to pre–T cell development, as does the subcapsular region of the thymus. Thus, we provide evidence of a role for the human tonsil in a comprehensive program of extrathymic T cell development. PMID:22378041

Postprandial Monocyte Activation in Individuals With Metabolic Syndrome

PubMed Central

Khan, Ilvira M.; Pokharel, Yashashwi; Dadu, Razvan T.; Lewis, Dorothy E.; Hoogeveen, Ron C.; Wu, Huaizhu

2016-01-01

Context: Postprandial hyperlipidemia has been suggested to contribute to atherogenesis by inducing proinflammatory changes in monocytes. Individuals with metabolic syndrome (MS), shown to have higher blood triglyceride concentration and delayed triglyceride clearance, may thus have increased risk for development of atherosclerosis. Objective: Our objective was to examine fasting levels and effects of a high-fat meal on phenotypes of monocyte subsets in individuals with obesity and MS and in healthy controls. Design, Setting, Participants, Intervention: Individuals with obesity and MS and gender- and age-matched healthy controls were recruited. Blood was collected from participants after an overnight fast (baseline) and at 3 and 5 hours after ingestion of a high-fat meal. At each time point, monocyte phenotypes were examined by multiparameter flow cytometry. Main Outcome Measures: Baseline levels of activation markers and postprandial inflammatory response in each of the three monocyte subsets were measured. Results: At baseline, individuals with obesity and MS had higher proportions of circulating lipid-laden foamy monocytes than controls, which were positively correlated with fasting triglyceride levels. Additionally, the MS group had increased counts of nonclassical monocytes, higher CD11c, CX3CR1, and human leukocyte antigen-DR levels on intermediate monocytes, and higher CCR5 and tumor necrosis factor-α levels on classical monocytes in the circulation. Postprandial triglyceride increases in both groups were paralleled by upregulation of lipid-laden foamy monocytes. MS, but not control, subjects had significant postprandial increases of CD11c and percentages of IL-1β+ and tumor necrosis factor-α+ cells in nonclassical monocytes. Conclusions: Compared to controls, individuals with obesity and MS had increased fasting and postprandial monocyte lipid accumulation and activation. PMID:27575945

QCD constituent counting rules for neutral vector mesons

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

Brodsky, Stanley J.; Lebed, Richard F.; Lyubovitskij, Valery E.

QCD constituent counting rules define the scaling behavior of exclusive hadronic scattering and electromagnetic scattering amplitudes at high momentum transfer in terms of the total number of fundamental constituents in the initial and final states participating in the hard subprocess. The scaling laws reflect the twist of the leading Fock state for each hadron and hence the leading operator that creates the composite state from the vacuum. Thus, the constituent counting scaling laws can be used to identify the twist of exotic hadronic candidates such as tetraquarks and pentaquarks. Effective field theories must consistently implement the scaling rules in ordermore » to be consistent with the fundamental theory. Here in this paper, we examine how one can apply constituent counting rules for the exclusive production of one or two neutral vector mesons V 0 in e + e - annihilation, processes in which the V 0 can couple via intermediate photons. In the case of a (narrow) real V 0, the photon virtuality is fixed to a precise value s 1 = m2V 0, thus treating the V 0 as a single fundamental particle. Each real V 0 thus contributes to the constituent counting rules with NV0 = 1 . In effect, the leading operator underlying the V 0 has twist 1. Thus, in the specific physical case of single or double on-shell V 0 production via intermediate photons, the predicted scaling from counting rules coincides with vector-meson dominance (VMD), an effective theory that treats V 0 as an elementary field. However, the VMD prediction fails in the general case where the V 0 is not coupled through an elementary photon field, and then the leading-twist interpolating operator has twist NV 0 = 2 . Analogous effects appear in pp scattering processes.« less

Sub-4 nm PtZn Intermetallic Nanoparticles for Enhanced Mass and Specific Activities in Catalytic Electrooxidation Reaction

DOE PAGES

Qi, Zhiyuan; Xiao, Chaoxian; Liu, Cong; ...

2017-03-08

Atomically ordered intermetallic nanoparticles (iNPs) have sparked considerable interest in fuel cell applications by virtue of their exceptional electronic and structural properties. However, the synthesis of small iNPs in a controllable manner remains a formidable challenge because of the high temperature generally required in the formation of intermetallic phases. Here in this paper we report a general method for the synthesis of PtZn iNPs (3.2 ± 0.4 nm) on multiwalled carbon nanotubes (MWNT) via a facile and capping agent free strategy using a sacrificial mesoporous silica (mSiO 2) shell. The as-prepared PtZn iNPs exhibited ca. 10 times higher mass activitymore » in both acidic and basic solution toward the methanol oxidation reaction (MOR) compared to larger PtZn iNPs synthesized on MWNT without the mSiO 2 shell. Density functional theory (DFT) calculations predict that PtZn systems go through a “non-CO” pathway for MOR because of the stabilization of the OH* intermediate by Zn atoms, while a pure Pt system forms highly stable COH* and CO* intermediates, leading to catalyst deactivation. Experimental studies on the origin of the backward oxidation peak of MOR coincide well with DFT predictions. Moreover, the calculations demonstrate that MOR on smaller PtZn iNPs is energetically more favorable than larger iNPs, due to their high density of corner sites and lower-lying energetic pathway. Therefore, smaller PtZn iNPs not only increase the number but also enhance the activity of the active sites in MOR compared with larger ones. This work opens a new avenue for the synthesis of small iNPs with more undercoordinated and enhanced active sites for fuel cell applications.« less

600 kyr of Hydrothermal Activity on the Cleft Segment of the Juan de Fuca Ridge

NASA Astrophysics Data System (ADS)

Middleton, J. L.; Mukhopadhyay, S.; Langmuir, C. H.; Costa, K.; McManus, J. F.; Katz, R. F.; Huybers, P. J.; Winckler, G.; Li, Y.

2017-12-01

Pressure fluctuations caused by glacially driven variations in sea level may modulate magmatic and hydrothermal output at submarine volcanic centers, with falling sea level driving increased volcanic activity. In turn, glacially paced changes in submarine volcanism could induce globally synchronous variations in the delivery of bioavailable iron and CO2 from mid-ocean ridges and thus provide solid-Earth feedbacks into the climate system. While evaluation of submarine volcanic output on orbital-timescales is technically challenging, near-ridge sediment cores hosting hydrothermal plume precipitates provide continuous, spatially integrated, and datable records to investigate the long-term behavior of hydrothermal systems. We will present new sedimentary records of hydrothermal variability spanning the past 600 kyr on the Cleft Segment of the Juan de Fuca Ridge in the Northeast Pacific. As an intermediate spreading-rate ridge, the Juan de Fuca Ridge is hypothesized to be particularly sensitive to sea level forcing at the Milankovitch frequencies of Pleistocene glacial cycles. Thus, the new records can be used to examine the connection between sea level and hydrothermal activity over multiple glacial cycles. Hydrothermal input is determined from iron and copper, with a titanium-based correction for lithogenic contributions. Sedimentary fluxes are then constrained using excess thorium-230 and extraterrestrial helium-3 as constant flux proxies. Preliminary results indicate 10-fold changes in hydrothermal iron and copper fluxes over the past 600 kyr and suggest a quasiperiodic variability in hydrothermal deposition on 100 to 120 kyr cycles. Comparison of the Juan de Fuca record with model predictions for an intermediate spreading ridge forced by Pleistocene glacial cycles finds frequent coincidence between predicted positive anomalies in magmatic output and observed peaks in hydrothermal deposition. This work encourages the continued exploration of the relationship between glacial cycles and submarine volcanic activity.

QCD constituent counting rules for neutral vector mesons

NASA Astrophysics Data System (ADS)

Brodsky, Stanley J.; Lebed, Richard F.; Lyubovitskij, Valery E.

2018-02-01

QCD constituent counting rules define the scaling behavior of exclusive hadronic scattering and electromagnetic scattering amplitudes at high momentum transfer in terms of the total number of fundamental constituents in the initial and final states participating in the hard subprocess. The scaling laws reflect the twist of the leading Fock state for each hadron and hence the leading operator that creates the composite state from the vacuum. Thus, the constituent counting scaling laws can be used to identify the twist of exotic hadronic candidates such as tetraquarks and pentaquarks. Effective field theories must consistently implement the scaling rules in order to be consistent with the fundamental theory. Here, we examine how one can apply constituent counting rules for the exclusive production of one or two neutral vector mesons V0 in e+e- annihilation, processes in which the V0 can couple via intermediate photons. In the case of a (narrow) real V0, the photon virtuality is fixed to a precise value s1=mV02, thus treating the V0 as a single fundamental particle. Each real V0 thus contributes to the constituent counting rules with NV0=1. In effect, the leading operator underlying the V0 has twist 1. Thus, in the specific physical case of single or double on-shell V0 production via intermediate photons, the predicted scaling from counting rules coincides with vector-meson dominance (VMD), an effective theory that treats V0 as an elementary field. However, the VMD prediction fails in the general case where the V0 is not coupled through an elementary photon field, and then the leading-twist interpolating operator has twist NV 0=2 . Analogous effects appear in p p scattering processes.

Spatial patterns of distribution, abundance, and species diversity of small odontocetes estimated using density surface modeling with line transect sampling

NASA Astrophysics Data System (ADS)

Kanaji, Yu; Okazaki, Makoto; Miyashita, Tomio

2017-06-01

Spatial patterns of distribution, abundance, and species diversity of small odontocetes including species in the Delphinidae and Phocoenidae families were investigated using long-term dedicated sighting survey data collected between 1983 and 2006 in the North Pacific. Species diversity indices were calculated from abundance estimated using density surface modeling of line-transect data. The estimated abundance ranged from 19,521 individuals in killer whale to 1,886,022 in pantropical spotted dolphin. The predicted density maps showed that the habitats of small odontocetes corresponded well with distinct oceanic domains. Species richness was estimated to be highest between 30 and 40°N where warm- and cold-water currents converge. Simpson's Diversity Index showed latitudinal diversity gradients of decreasing species numbers toward the poles. Higher diversity was also estimated in the coastal areas and the zonal areas around 35-42°N. Coastal-offshore gradients and latitudinal gradients are known for many taxa. The zonal areas around 35°N and 40°N coincide with the Kuroshio Current and its extension and the subarctic boundary, respectively. These results suggest that the species diversity of small odontocetes primarily follows general patterns of latitudinal and longitudinal gradients, while the confluence of faunas originating in distinct water masses increases species diversify in frontal waters around 30-40°N. Population densities tended to be higher for the species inhabiting higher latitudes, but were highest for intermediate latitudes at approximately 35-40°N. According to latitudinal gradients in water temperature and biological productivity, the costs for thermoregulation will decrease in warmer low latitudes, while feeding efficiency will increase in colder high latitudes. These trade-offs could optimize population density in intermediate latitudes.

QCD constituent counting rules for neutral vector mesons

DOE PAGES

Brodsky, Stanley J.; Lebed, Richard F.; Lyubovitskij, Valery E.

2018-02-08

QCD constituent counting rules define the scaling behavior of exclusive hadronic scattering and electromagnetic scattering amplitudes at high momentum transfer in terms of the total number of fundamental constituents in the initial and final states participating in the hard subprocess. The scaling laws reflect the twist of the leading Fock state for each hadron and hence the leading operator that creates the composite state from the vacuum. Thus, the constituent counting scaling laws can be used to identify the twist of exotic hadronic candidates such as tetraquarks and pentaquarks. Effective field theories must consistently implement the scaling rules in ordermore » to be consistent with the fundamental theory. Here in this paper, we examine how one can apply constituent counting rules for the exclusive production of one or two neutral vector mesons V 0 in e + e - annihilation, processes in which the V 0 can couple via intermediate photons. In the case of a (narrow) real V 0, the photon virtuality is fixed to a precise value s 1 = m2V 0, thus treating the V 0 as a single fundamental particle. Each real V 0 thus contributes to the constituent counting rules with NV0 = 1 . In effect, the leading operator underlying the V 0 has twist 1. Thus, in the specific physical case of single or double on-shell V 0 production via intermediate photons, the predicted scaling from counting rules coincides with vector-meson dominance (VMD), an effective theory that treats V 0 as an elementary field. However, the VMD prediction fails in the general case where the V 0 is not coupled through an elementary photon field, and then the leading-twist interpolating operator has twist NV 0 = 2 . Analogous effects appear in pp scattering processes.« less

Influence on Visual Quality of Intraoperative Orientation of Asymmetric Intraocular Lenses.

PubMed

Bonaque-González, Sergio; Ríos, Susana; Amigó, Alfredo; López-Gil, Norberto

2015-10-01

To evaluate visual quality when changing the intraocular orientation of the Lentis Mplus LS-312MF nonrotational symmetric +3.00 diopters aspheric multifocal intraocular lens ([IOL] Oculentis GmbH, Berlin, Germany) in normal eyes. An artificial eye was used to measure the in vitro wavefront of the IOL. The corneal topography of 20 healthy patients was obtained. For each eye, a computational analysis simulated the implantation of the IOL. The modulation transfer function (MTF) and an image quality parameter (visually modulated transfer function [VSMTF] metric) were calculated for a 5.0-mm pupil and for three conditions: distance, intermediate, and near vision. The procedure was repeated for each eye after a rotation of the IOL with respect to the cornea from 0° to 360° in 1° steps. Statistical analysis showed significant differences in mean VSMTF values between orientations for distance vision. Optimal orientation of the IOL (different for each eye) showed a mean improvement of 58% ± 19% (range: 20% to 121%) in VSMTF values with respect to the worst possible orientation. For these orientations, intermediate and near vision quality were statistically indistinguishable. The MTFs were different between orientations, showing a mean difference of approximately 5 cycles per degree in the maximum spatial frequencies that can be transferred between the best and the worst orientations for distance vision. The results suggest that implantation of this nonrotational symmetric IOL should improve visual outcomes if it is oriented to coincide with a customized meridian. A simple, practical method is proposed to find an approximation to the angle that an Mplus IOL should be inserted. Copyright 2015, SLACK Incorporated.

Cardiac computed tomography in patients with symptomatic new-onset atrial fibrillation, rule-out acute coronary syndrome, but with intermediate pretest probability for coronary artery disease admitted to a chest pain unit.

PubMed

Koopmann, Matthias; Hinrichs, Liane; Olligs, Jan; Lichtenberg, Michael; Eckardt, Lars; Böse, Dirk; Möhlenkamp, Stefan; Waltenberger, Johannes; Breuckmann, Frank

2018-01-24

Atrial fibrillation (AF) and coronary artery disease (CAD) may be encountered coincidently in a large portion of patients. However, data on coronary artery calcium burden in such patients are lacking. Thus, we sought to determine the value of cardiac computed tomography (CCT) in patients presenting with new-onset AF associated with an intermediate pretest probability for CAD admitted to a chest pain unit (CPU). Calcium scores (CS) of 73 new-onset, symptomatic AF subjects without typical clinical, electrocardiographic, or laboratory signs of acute coronary syndrome (ACS) admitted to our CPU were analyzed. In addition, results from computed tomography angiography (CTA) were related to coronary angiography findings whenever available. Calcium scores of zero were found in 25%. Median Agatston score was 77 (interquartile range: 1-270) with gender- and territory-specific dispersal. CS scores above average were present in about 50%, high (> 400)-to-very high (> 1000) CS scores were found in 22%. Overall percentile ranking showed a relative accordance to the reference percentile distribution. Additional CTA was performed in 47%, revealing stenoses in 12%. Coronary angiography was performed in 22% and resulted in coronary intervention or surgical revascularization in 7%. On univariate analysis, CS > 50th percentile failed to serve as an independent determinant of significant stenosis during catheterization. Within a CPU setting, relevant CAD was excluded or confirmed in almost 50%, the latter with a high proportion of coronary angiographies and subsequent coronary interventions, underlining the diagnostic value of CCT in symptomatic, non-ACS, new-onset AF patients when admitted to a CPU.

Neural correlates of visualizations of concrete and abstract words in preschool children: a developmental embodied approach

PubMed Central

D’Angiulli, Amedeo; Griffiths, Gordon; Marmolejo-Ramos, Fernando

2015-01-01

The neural correlates of visualization underlying word comprehension were examined in preschool children. On each trial, a concrete or abstract word was delivered binaurally (part 1: post-auditory visualization), followed by a four-picture array (a target plus three distractors; part 2: matching visualization). Children were to select the picture matching the word they heard in part 1. Event-related potentials (ERPs) locked to each stimulus presentation and task interval were averaged over sets of trials of increasing word abstractness. ERP time-course during both parts of the task showed that early activity (i.e., <300 ms) was predominant in response to concrete words, while activity in response to abstract words became evident only at intermediate (i.e., 300–699 ms) and late (i.e., 700–1000 ms) ERP intervals. Specifically, ERP topography showed that while early activity during post-auditory visualization was linked to left temporo-parietal areas for concrete words, early activity during matching visualization occurred mostly in occipito-parietal areas for concrete words, but more anteriorly in centro-parietal areas for abstract words. In intermediate ERPs, post-auditory visualization coincided with parieto-occipital and parieto-frontal activity in response to both concrete and abstract words, while in matching visualization a parieto-central activity was common to both types of words. In the late ERPs for both types of words, the post-auditory visualization involved right-hemispheric activity following a “post-anterior” pathway sequence: occipital, parietal, and temporal areas; conversely, matching visualization involved left-hemispheric activity following an “ant-posterior” pathway sequence: frontal, temporal, parietal, and occipital areas. These results suggest that, similarly, for concrete and abstract words, meaning in young children depends on variably complex visualization processes integrating visuo-auditory experiences and supramodal embodying representations. PMID:26175697

Sub-4 nm PtZn Intermetallic Nanoparticles for Enhanced Mass and Specific Activities in Catalytic Electrooxidation Reaction

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

Qi, Zhiyuan; Xiao, Chaoxian; Liu, Cong

2017-03-22

Atomically ordered intermetallic nanoparticles (iNPs) have sparked considerable interest in fuel cell applications by virtue of their exceptional electronic and structural properties. However, the synthesis of small iNPs in a controllable manner remains a formidable challenge because of the high temperature generally required in the formation of intermetallic phases. Here we report a general method for the synthesis of PtZn. iNPs (3.2 +/- 0.4 nm) on multiwalled carbon nanotubes (MWNT) via a facile and capping agent free strategy using a sacrificial mesoporous silica (mSiO(2)) shell. The as-prepared PtZn iNPs exhibited ca. 10 times higher mass activity in both acidic andmore » basic solution toward the methanol oxidation reaction (MOR) compared to larger PtZn iNPs synthesized on MWNT without the mSiO2 shell. Density functional theory (DFT) calculations predict that PtZn systems go through a "non-CO" pathway for MOR because of the stabilization of the OH* intermediate by Zn atoms, while a pure Pt system forms highly stable COH* and CO* intermediates, leading to catalyst deactivation. Experimental studies on the origin of the backward oxidation peak of MOR coincide well with DFT predictions. Moreover, the calculations demonstrate that MOR on smaller PtZn iNPs is energetically more favorable than larger iNPs, due to their high density of corner sites and lower-lying energetic pathway. Therefore, smaller PtZn iNPs not only increase the number but also enhance the activity of the active sites in MOR compared with larger ones. This work opens a new avenue for the synthesis of small iNPs with more undercoordinated and enhanced active sites for fuel cell applications.« less

Biology of Thelazia callipaeda (Spirurida, Thelaziidae) eyeworms in naturally infected definitive hosts.

PubMed

Otranto, D; Lia, R P; Buono, V; Traversa, D; Giangaspero, A

2004-11-01

Thelazia callipaeda (Spirurida, Thelaziidae) eyeworm causes ocular infection in carnivores and humans in the Far East; this infection has been recently reported also in Europe--northern and southern Italy--in dogs, cats and foxes. The natural vector/s of T. callipaeda is/are unknown and the development of the nematode in its definitive hosts is limited to an experimental trial on dogs. To contribute new insights into the development of T. callipaeda in the definitive host in field conditions, eyeworms were collected from naturally infected dogs from an area with a high prevalence of infection (up to 60.14%) in the Basilicata region of southern Italy, from January 2002 to December 2003. Conjunctival secretions were also collected and examined for the presence of immature stages. The presence of blastomerized eggs throughout the period--except for the months from May to November--indicates a seasonality in the reproductive activity of T. callipaeda, coinciding with the presence/absence of the vector. In fact, 1st-stage larvae were found in the lachrymal secretions of dogs in summer (June--July 2002 and 2003), ready to be ingested by flies feeding about the eyes. The evidence of 4th-stage larvae in March 2002 and April, July and October 2003 may be accounted for by the presence of flies that act as intermediate hosts of T. callipaeda from early spring to early autumn. The presence of immature stages in October indicates an overlapping generation of nematodes and a 2nd cycle of vector infection. This basic knowledge of the development of T. callipaeda will hopefully help future epidemiological studies to identify the intermediate hosts and define the likely risk for vectors in field conditions.

Measuring Transmission Efficiencies Of Mass Spectrometers

NASA Technical Reports Server (NTRS)

Srivastava, Santosh K.

1989-01-01

Coincidence counts yield absolute efficiencies. System measures mass-dependent transmission efficiencies of mass spectrometers, using coincidence-counting techniques reminiscent of those used for many years in calibration of detectors for subatomic particles. Coincidences between detected ions and electrons producing them counted during operation of mass spectrometer. Under certain assumptions regarding inelastic scattering of electrons, electron/ion-coincidence count is direct measure of transmission efficiency of spectrometer. When fully developed, system compact, portable, and used routinely to calibrate mass spectrometers.

Enhanced Product Generation at NASA Data Centers Through Grid Technology

NASA Technical Reports Server (NTRS)

Barkstrom, Bruce R.; Hinke, Thomas H.; Gavali, Shradha; Seufzer, William J.

2003-01-01

This paper describes how grid technology can support the ability of NASA data centers to provide customized data products. A combination of grid technology and commodity processors are proposed to provide the bandwidth necessary to perform customized processing of data, with customized data subsetting providing the initial example. This customized subsetting engine can be used to support a new type of subsetting, called phenomena-based subsetting, where data is subsetted based on its association with some phenomena, such as mesoscale convective systems or hurricanes. This concept is expanded to allow the phenomena to be detected in one type of data, with the subsetting requirements transmitted to the subsetting engine to subset a different type of data. The subsetting requirements are generated by a data mining system and transmitted to the subsetter in the form of an XML feature index that describes the spatial and temporal extent of the phenomena. For this work, a grid-based mining system called the Grid Miner is used to identify the phenomena and generate the feature index. This paper discusses the value of grid technology in facilitating the development of a high performance customized product processing and the coupling of a grid mining system to support phenomena-based subsetting.

Low level radioactivity measurements with phoswich detectors using coincident techniques and digital pulse processing analysis.

PubMed

de la Fuente, R; de Celis, B; del Canto, V; Lumbreras, J M; de Celis Alonso, B; Martín-Martín, A; Gutierrez-Villanueva, J L

2008-10-01

A new system has been developed for the detection of low radioactivity levels of fission products and actinides using coincidence techniques. The device combines a phoswich detector for alpha/beta/gamma-ray recognition with a fast digital card for electronic pulse analysis. The phoswich can be used in a coincident mode by identifying the composed signal produced by the simultaneous detection of alpha/beta particles and X-rays/gamma particles. The technique of coincidences with phoswich detectors was proposed recently to verify the Nuclear Test Ban Treaty (NTBT) which established the necessity of monitoring low levels of gaseous fission products produced by underground nuclear explosions. With the device proposed here it is possible to identify the coincidence events and determine the energy and type of coincident particles. The sensitivity of the system has been improved by employing liquid scintillators and a high resolution low energy germanium detector. In this case it is possible to identify simultaneously by alpha/gamma coincidence transuranic nuclides present in environmental samples without necessity of performing radiochemical separation. The minimum detectable activity was estimated to be 0.01 Bq kg(-1) for 0.1 kg of soil and 1000 min counting.

Digital gamma-gamma coincidence HPGe system for environmental analysis.

PubMed

Marković, Nikola; Roos, Per; Nielsen, Sven Poul

2017-08-01

The performance of a new gamma-gamma coincidence spectrometer system for environmental samples analysis at the Center for Nuclear Technologies of the Technical University of Denmark (DTU) is reported. Nutech Coincidence Low Energy Germanium Sandwich (NUCLeGeS) system consists of two HPGe detectors in a surface laboratory with a digital acquisition system used to collect the data in time-stamped list mode with 10ns time resolution. The spectrometer is used in both anticoincidence and coincidence modes. Copyright © 2017 Elsevier Ltd. All rights reserved.

A tandem time–of–flight spectrometer for negative–ion/positive–ion coincidence measurements with soft x-ray excitation

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

Stråhlman, Christian, E-mail: Christian.Strahlman@maxlab.lu.se; Sankari, Rami; Nyholm, Ralf

2016-01-15

We present a newly constructed spectrometer for negative–ion/positive–ion coincidence spectroscopy of gaseous samples. The instrument consists of two time–of–flight ion spectrometers and a magnetic momentum filter for deflection of electrons. The instrument can measure double and triple coincidences between mass–resolved negative and positive ions with high detection efficiency. First results include identification of several negative–ion/positive–ion coincidence channels following inner-shell photoexcitation of sulfur hexafluoride (SF{sub 6})

Stable isotope stratigraphy of Latest Miocene sequences in northwest Morocco: The Bou Regreg section

NASA Astrophysics Data System (ADS)

Hodell, David A.; Benson, Richard H.; Kennett, James P.; Rakic-El Bied, Kruna

1989-08-01

Oxygen and carbon isotopic ratios of foraminifers were measured from outcrop and drill core sequences from the Bou Regreg Section, northwest Morocco. This composite section was located at the western end of the Rifian Corridor during the late Miocene and thus potentially contains a record of water exchange between the Atlantic and Mediterranean during the late Tortonian and Messinian stages. Here we correlate isotopic and sedimentologic events in the Bou Regreg Section with Mediterranean and deep-sea sequences during the time leading up to and including the deposition of the Messinian evaporites. The late Miocene chron 6 carbon shift was identified in two Moroccan sequences, providing a valuable 6.3-Ma datum level. In both sections, the carbon shift coincides with the first occurrence of Globorotalia conomiozea and the Tortonian/Messinian boundary. Near this boundary, a major faunal turnover occurred in ostracod, planktonic foraminiferal, and nannofossil assemblages that indicates a cooling of surface and deep water in the Rifian Corridor. At 6.1 Ma, just above the Tortonian/Messinian boundary, mean ∂18O values of benthic foraminifers increased by 0.4-0.5‰ suggesting decreased temperature and/or increased continental ice volume. The faunal and isotopic changes are interpreted as reflecting a reversal in the direction of deep water flow through the Rifian Corridor that occurred between 6.3 and 6.1 Ma. At this time, cold, nutrient-rich waters filled the Mediterranean basins from intermediate depths of the Atlantic, and the production of Mediterranean Outflow Water ceased. The upwelling of nutrient-rich Atlantic intermediate water stimulated productivity in the Mediterranean, which led to the deposition of organic-rich strata such as those found in the Tripoli Formation. At ˜5.5 Ma, coincident with a coiling shift in Neogloboquadrina acostaensis, the variability of the benthic ∂18O signal increased markedly, and strong color variations appeared in the sediments (alternating between red and blue marls). These isotopic and sedimentologic changes at Bou Regreg represented markedly fluctuating oceanographic conditions in the Rifian Corridor between 5.5 and 4.8 Ma. We speculate that these cycles were related to sea level variations that controlled the periodic influx of marine water into the Mediterranean during the time of evaporite deposition. The onset of these cycles occurred at 5.5 Ma and is correlated to a eustatic fall in sea level at the base of the Caliza Tosca Formation in Carmona, Spain, and to the base of the lowermost evaporite unit in the Mediterranean (e.g., Calcare di Base in Sicily). In this proposed scenario, the duration of the Messinian salinity crisis was 700,000 years and lasted between 5.5 and 4.8 Ma.

Averaging processes in granular flows driven by gravity

NASA Astrophysics Data System (ADS)

Rossi, Giulia; Armanini, Aronne

2016-04-01

One of the more promising theoretical frames to analyse the two-phase granular flows is offered by the similarity of their rheology with the kinetic theory of gases [1]. Granular flows can be considered a macroscopic equivalent of the molecular case: the collisions among molecules are compared to the collisions among grains at a macroscopic scale [2,3]. However there are important statistical differences in dealing with the two applications. In the two-phase fluid mechanics, there are two main types of average: the phasic average and the mass weighed average [4]. The kinetic theories assume that the size of atoms is so small, that the number of molecules in a control volume is infinite. With this assumption, the concentration (number of particles n) doesn't change during the averaging process and the two definitions of average coincide. This hypothesis is no more true in granular flows: contrary to gases, the dimension of a single particle becomes comparable to that of the control volume. For this reason, in a single realization the number of grain is constant and the two averages coincide; on the contrary, for more than one realization, n is no more constant and the two types of average lead to different results. Therefore, the ensamble average used in the standard kinetic theory (which usually is the phasic average) is suitable for the single realization, but not for several realization, as already pointed out in [5,6]. In the literature, three main length scales have been identified [7]: the smallest is the particles size, the intermediate consists in the local averaging (in order to describe some instability phenomena or secondary circulation) and the largest arises from phenomena such as large eddies in turbulence. Our aim is to solve the intermediate scale, by applying the mass weighted average, when dealing with more than one realizations. This statistical approach leads to additional diffusive terms in the continuity equation: starting from experimental results, we aim to define the scales governing the diffusive phenomenon, introducing the diffusive terms following the Boussinesq model. The diffusive coefficient will be experimentally defined; it will be probably proportional to the square root of the granular temperature θ and the diameter of the particles d or, alternatively, the flow height h. REFERENCES 1 Chapman S., Cowling T.G., 1971. Cambridge University Press, Cambridge, England. 2 Jenkins J.T., Savage S.B., 1983 J. Fluid.Mech., 130: 187-202 3 Savage S.B.,1984. J. Fluid.Mech., 24: 289-366 4 D.A.Drew, 1983. Annu. Rev. Fluid Mech. 15:261-291 5 I. Goldhirsch, 2003. Annu. Rev. Fluid Mech., 35:267-293. 6 I. Goldhirsch, 2008. Powder Technology, 182: 130-136. 7 T.J. Hsu, J.T. Jenkins, P.L. Liu 2004. Proc. Royal Soc.

γγ coincidence spectrometer for instrumental neutron-activation analysis

NASA Astrophysics Data System (ADS)

Tomlin, B. E.; Zeisler, R.; Lindstrom, R. M.

2008-05-01

Neutron-activation analysis (NAA) is an important technique for the accurate and precise determination of trace and ultra-trace elemental compositions. The application of γγ coincidence counting to NAA in order to enhance specificity was first explored over 40 years ago but has not evolved into a regularly used technique. A γγ coincidence spectrometer has been constructed at the National Institute of Standards and Technology, using two HPGe γ-ray detectors and an all-digital data-acquisition system, for the purpose of exploring coincidence NAA and its value in characterizing reference materials. This paper describes the initial evaluation of the quantitative precision of coincidence counting versus singles spectrometry, based upon a sample of neutron-irradiated bovine liver material.

';Best' Practices for Aggregating Subset Results from Archived Datasets

NASA Astrophysics Data System (ADS)

Baskin, W. E.; Perez, J.

2013-12-01

In response to the exponential growth in science data analysis and visualization capabilities Data Centers have been developing new delivery mechanisms to package and deliver large volumes of aggregated subsets of archived data. New standards are evolving to help data providers and application programmers deal with growing needs of the science community. These standards evolve from the best practices gleaned from new products and capabilities. The NASA Atmospheric Sciences Data Center (ASDC) has developed and deployed production provider-specific search and subset web applications for the CALIPSO, CERES, TES, and MOPITT missions. This presentation explores several use cases that leverage aggregated subset results and examines the standards and formats ASDC developers applied to the delivered files as well as the implementation strategies for subsetting and processing the aggregated products. The following topics will be addressed: - Applications of NetCDF CF conventions to aggregated level 2 satellite subsets - Data-Provider-Specific format requirements vs. generalized standards - Organization of the file structure of aggregated NetCDF subset output - Global Attributes of individual subsetted files vs. aggregated results - Specific applications and framework used for subsetting and delivering derivative data files

Characteristics of CD8+ T cell subsets in Chinese patients with chronic HIV infection during initial ART.

PubMed

Jiao, Yanmei; Hua, Wei; Zhang, Tong; Zhang, Yonghong; Ji, Yunxia; Zhang, Hongwei; Wu, Hao

2011-03-25

CD8+ T cells may play an important role in protecting against HIV. However, the changes of CD8+ T cell subsets during early period of ART have not been fully studied. Twenty-one asymptomatic treatment-naive HIV-infected patients with CD4 T+ cells less than 350 cells/μl were enrolled in the study. Naïve, central memory(CM), effective memory(EM) and terminally differentiated effector (EMRA) CD8+ cell subsets and their activation and proliferation subsets were evaluated in blood samples collected at base line, and week 2, 4, 8 and 12 of ART. The total CD8+ T cells declined and the Naïve and CM subsets had a tendency of increase. Activation levels of all CD8+ T cell subsets except EMRA subset decreased after ART. However, proliferation levels of total CD8+ T cells, EMRA, EM and CM subsets increased at the first 4 weeks of ART, then decreased. Proliferation level of the naïve cells decreased after ART. The changes of CD8+ T cell subsets during initial ART are complex. Our results display a complete phenotypical picture of CD8+ cell subsets during initial ART and provide insights for understanding of immune status during ART.

Characteristics of CD8+ T cell subsets in Chinese patients with chronic HIV infection during initial ART

PubMed Central

2011-01-01

Background CD8+ T cells may play an important role in protecting against HIV. However, the changes of CD8+ T cell subsets during early period of ART have not been fully studied. Methods Twenty-one asymptomatic treatment-naive HIV-infected patients with CD4 T+ cells less than 350 cells/μl were enrolled in the study. Naïve, central memory(CM), effective memory(EM) and terminally differentiated effector (EMRA) CD8+ cell subsets and their activation and proliferation subsets were evaluated in blood samples collected at base line, and week 2, 4, 8 and 12 of ART. Results The total CD8+ T cells declined and the Naïve and CM subsets had a tendency of increase. Activation levels of all CD8+ T cell subsets except EMRA subset decreased after ART. However, proliferation levels of total CD8+ T cells, EMRA, EM and CM subsets increased at the first 4 weeks of ART, then decreased. Proliferation level of the naïve cells decreased after ART. Conclusion The changes of CD8+ T cell subsets during initial ART are complex. Our results display a complete phenotypical picture of CD8+ cell subsets during initial ART and provide insights for understanding of immune status during ART. PMID:21435275

Earth-Moon Impacts at 300 Ma and 500 Ma Ago

NASA Technical Reports Server (NTRS)

Zellner, N. E. B.; Delano, J. W.; Swindle, T. D.; Barra, F.; Whittet, D. C. B.; Spudis, P. D.

2005-01-01

Impact events have played an important role in the evolution of planets and small bodies in the Solar System. Meteorites, lunar melt rocks, and lunar impact glasses provide important information about the geology of the parent body and the age of the impacting episodes. Over 2400 impact glasses from 4 Apollo regolith samples have been geochemically analyzed and a subset has been dated by the (40)Ar/(39)Ar method. New results, consistent with 2 break-ups in the Asteroid Belt, are presented here. Our previous study reported that (40)Ar/(39)Ar ages from 9 impact glasses showed that the Moon experienced significant impacts at approx. 800 Ma and at approx. 3800 Ma ago, somewhere in the vicinity of the Apollo 16 landing site. Additionally, reported on Apollo 12 samples with ages around 800 Ma, together implying global bombardment events. New data on 7 glasses from regolith sample 66041,127 show that the Moon also experienced impact events at approx. 300 Ma and > 500 Ma ago, which may coincide with the break-ups in the Asteroid Belt of the L- and H-chrondrite parent bodies. Since meteoritic evidence for these breakups has been found on Earth, it follows that evidence should be found in lunar samples as well. Additional information is included in the original extended abstract.

Continental-scale Validation of MODIS-based and LEDAPS Landsat ETM+ Atmospheric Correction Methods

NASA Technical Reports Server (NTRS)

Ju, Junchang; Roy, David P.; Vermote, Eric; Masek, Jeffrey; Kovalskyy, Valeriy

2012-01-01

The potential of Landsat data processing to provide systematic continental scale products has been demonstrated by several projects including the NASA Web-enabled Landsat Data (WELD) project. The recent free availability of Landsat data increases the need for robust and efficient atmospheric correction algorithms applicable to large volume Landsat data sets. This paper compares the accuracy of two Landsat atmospheric correction methods: a MODIS-based method and the Landsat Ecosystem Disturbance Adaptive Processing System (LEDAPS) method. Both methods are based on the 6SV radiative transfer code but have different atmospheric characterization approaches. The MODIS-based method uses the MODIS Terra derived dynamic aerosol type, aerosol optical thickness, and water vapor to atmospherically correct ETM+ acquisitions in each coincident orbit. The LEDAPS method uses aerosol characterizations derived independently from each Landsat acquisition and assumes a fixed continental aerosol type and uses ancillary water vapor. Validation results are presented comparing ETM+ atmospherically corrected data generated using these two methods with AERONET corrected ETM+ data for 95 10 km×10 km 30 m subsets, a total of nearly 8 million 30 m pixels, located across the conterminous United States. The results indicate that the MODIS-based method has better accuracy than the LEDAPS method for the ETM+ red and longer wavelength bands.

The role of trigeminal nasal TRPM8-expressing afferent neurons in the antitussive effects of menthol.

PubMed

Plevkova, J; Kollarik, M; Poliacek, I; Brozmanova, M; Surdenikova, L; Tatar, M; Mori, N; Canning, B J

2013-07-15

The cold-sensitive cation channel TRPM8 is a target for menthol, which is used routinely as a cough suppressant and as an additive to tobacco and food products. Given that cold temperatures and menthol activate neurons through gating of TRPM8, it is unclear how menthol actively suppresses cough. In this study we describe the antitussive effects of (-)-menthol in conscious and anesthetized guinea pigs. In anesthetized guinea pigs, cough evoked by citric acid applied topically to the tracheal mucosa was suppressed by menthol only when it was selectively administered as vapors to the upper airways. Menthol applied topically to the tracheal mucosa prior to and during citric acid application or administered continuously as vapors or as an aerosol to the lower airways was without effect on cough. These actions of upper airway menthol treatment were mimicked by cold air delivered to the upper airways but not by (+)-menthol, the inactive isomer of menthol, or by the TRPM8/TRPA1 agonist icilin administered directly to the trachea. Subsequent molecular analyses confirmed the expression of TRPM8 in a subset of nasal trigeminal afferent neurons that do not coincidently express TRPA1 or TRPV1. We conclude that menthol suppresses cough evoked in the lower airways primarily through a reflex initiated from the nose.

Particle acceleration areas in two radio galaxies.

NASA Astrophysics Data System (ADS)

Andernach, H.

1989-04-01

Two edge-darkened, tailed radio galaxies (PKS 0123-01 and PKS 2247+11) were mapped with the VLA at 1.4 and 5 GHz at sub-arcmin resolution as well as with the Effelsberg 100-m telescope at 2.7, 5 and 10.7 GHz at arcmin resolution. With additional use of existing low-frequency maps the shape of the radio spectrum is analyzed point by point across the source extent. The shape is found to be concave (i.e. having high-frequency excess) over major parts of the source extent, in the case of 2247+11 even for a region in the far radio tail. Possible mechanisms causing this feature are proposed. Using a subset of maps at higher angular resolution most of the regions with spectral flattening turn out to coincide with bends and wiggles of the radio jets and/or tails. Polarization data are available at four frequencies and some problems in their interpretation are discussed. The following one consists of a 1-page "extended abstract" including two small figures. I attach to this message the processed postscript file which I would be happy to offer in ADS as a "scanned" paper. I include here the full extended abstract text which you could also offer as HTML code. I converted the four references to bibcodes.

Climate change and body size shift in Mediterranean bivalve assemblages: unexpected role of biological invasions.

PubMed

Nawrot, Rafał; Albano, Paolo G; Chattopadhyay, Devapriya; Zuschin, Martin

2017-08-16

Body size is a synthetic functional trait determining many key ecosystem properties. Reduction in average body size has been suggested as one of the universal responses to global warming in aquatic ecosystems. Climate change, however, coincides with human-enhanced dispersal of alien species and can facilitate their establishment. We address effects of species introductions on the size structure of recipient communities using data on Red Sea bivalves entering the Mediterranean Sea through the Suez Canal. We show that the invasion leads to increase in median body size of the Mediterranean assemblage. Alien species are significantly larger than native Mediterranean bivalves, even though they represent a random subset of the Red Sea species with respect to body size. The observed patterns result primarily from the differences in the taxonomic composition and body-size distributions of the source and recipient species pools. In contrast to the expectations based on the general temperature-size relationships in marine ectotherms, continued warming of the Mediterranean Sea indirectly leads to an increase in the proportion of large-bodied species in bivalve assemblages by accelerating the entry and spread of tropical aliens. These results underscore complex interactions between changing climate and species invasions in driving functional shifts in marine ecosystems. © 2017 The Author(s).

Massive plasmablast response elicited in the acute phase of hantavirus pulmonary syndrome.

PubMed

García, Marina; Iglesias, Ayelén; Landoni, Verónica I; Bellomo, Carla; Bruno, Agostina; Córdoba, María Teresa; Balboa, Luciana; Fernández, Gabriela C; Sasiain, María Del Carmen; Martínez, Valeria P; Schierloh, Pablo

2017-05-01

Beside its key diagnostic value, the humoral immune response is thought to play a protective role in hantavirus pulmonary syndrome. However, little is known about the cell source of these antibodies during ongoing human infection. Herein we characterized B-cell subsets circulating in Andes-virus-infected patients. A notable potent plasmablast (PB) response that increased 100-fold over the baseline levels was observed around 1 week after the onset of symptoms. These PB present a CD3 neg CD19 low CD20 neg CD38 hi CD27 hi CD138 +/- IgA +/- surface phenotype together with the presence of cytoplasmic functional immunoglobulins. They are large lymphocytes (lymphoblasts) morphologically coincident with the 'immunoblast-like' cells that have been previously described during blood cytology examinations of hantavirus-infected patients. Immunoreactivity analysis of white blood cell lysates suggests that some circulating PB are virus-specific but we also observed a significant increase of reactivity against virus-unrelated antigens, which suggests a possible bystander effect by polyclonal B-cell activation. The presence of this large and transient PB response raises the question as to whether these cells might have a protective or pathological role during the ongoing hantavirus pulmonary syndrome and suggest their practical application as a diagnostic/prognostic biomarker. © 2017 John Wiley & Sons Ltd.

The Epoxyeicosatrienoic Acid Pathway Enhances Hepatic Insulin Signaling and is Repressed in Insulin-Resistant Mouse Liver*

PubMed Central

Schäfer, Alexander; Neschen, Susanne; Kahle, Melanie; Sarioglu, Hakan; Gaisbauer, Tobias; Imhof, Axel; Adamski, Jerzy; Hauck, Stefanie M.; Ueffing, Marius

2015-01-01

Although it is widely accepted that ectopic lipid accumulation in the liver is associated with hepatic insulin resistance, the underlying molecular mechanisms have not been well characterized. Here we employed time resolved quantitative proteomic profiling of mice fed a high fat diet to determine which pathways were affected during the transition of the liver to an insulin-resistant state. We identified several metabolic pathways underlying altered protein expression. In order to test the functional impact of a critical subset of these alterations, we focused on the epoxyeicosatrienoic acid (EET) eicosanoid pathway, whose deregulation coincided with the onset of hepatic insulin resistance. These results suggested that EETs may be positive modulators of hepatic insulin signaling. Analyzing EET activity in primary hepatocytes, we found that EETs enhance insulin signaling on the level of Akt. In contrast, EETs did not influence insulin receptor or insulin receptor substrate-1 phosphorylation. This effect was mediated through the eicosanoids, as overexpression of the deregulated enzymes in absence of arachidonic acid had no impact on insulin signaling. The stimulation of insulin signaling by EETs and depression of the pathway in insulin resistant liver suggest a likely role in hepatic insulin resistance. Our findings support therapeutic potential for inhibiting EET degradation. PMID:26070664

Integrating Genomic Analysis with the Genetic Basis of Gene Expression: Preliminary Evidence of the Identification of Causal Genes for Cardiovascular and Metabolic Traits Related to Nutrition in Mexicans123

PubMed Central

Bastarrachea, Raúl A.; Gallegos-Cabriales, Esther C.; Nava-González, Edna J.; Haack, Karin; Voruganti, V. Saroja; Charlesworth, Jac; Laviada-Molina, Hugo A.; Veloz-Garza, Rosa A.; Cardenas-Villarreal, Velia Margarita; Valdovinos-Chavez, Salvador B.; Gomez-Aguilar, Patricia; Meléndez, Guillermo; López-Alvarenga, Juan Carlos; Göring, Harald H. H.; Cole, Shelley A.; Blangero, John; Comuzzie, Anthony G.; Kent, Jack W.

2012-01-01

Whole-transcriptome expression profiling provides novel phenotypes for analysis of complex traits. Gene expression measurements reflect quantitative variation in transcript-specific messenger RNA levels and represent phenotypes lying close to the action of genes. Understanding the genetic basis of gene expression will provide insight into the processes that connect genotype to clinically significant traits representing a central tenet of system biology. Synchronous in vivo expression profiles of lymphocytes, muscle, and subcutaneous fat were obtained from healthy Mexican men. Most genes were expressed at detectable levels in multiple tissues, and RNA levels were correlated between tissue types. A subset of transcripts with high reliability of expression across tissues (estimated by intraclass correlation coefficients) was enriched for cis-regulated genes, suggesting that proximal sequence variants may influence expression similarly in different cellular environments. This integrative global gene expression profiling approach is proving extremely useful for identifying genes and pathways that contribute to complex clinical traits. Clearly, the coincidence of clinical trait quantitative trait loci and expression quantitative trait loci can help in the prioritization of positional candidate genes. Such data will be crucial for the formal integration of positional and transcriptomic information characterized as genetical genomics. PMID:22797999

Hypothesis on supine sleep, sudden infant death syndrome reduction and association with increasing autism incidence

PubMed Central

Bergman, Nils J

2016-01-01

AIM To identify a hypothesis on: Supine sleep, sudden infant death syndrome (SIDS) reduction and association with increasing autism incidence. METHODS Literature was searched for autism spectrum disorder incidence time trends, with correlation of change-points matching supine sleep campaigns. A mechanistic model expanding the hypothesis was constructed based on further review of epidemiological and other literature on autism. RESULTS In five countries (Denmark, United Kingdom, Australia, Israel, United States) with published time trends of autism, change-points coinciding with supine sleep campaigns were identified. The model proposes that supine sleep does not directly cause autism, but increases the likelihood of expression of a subset of autistic criteria in individuals with genetic susceptibility, thereby specifically increasing the incidence of autism without intellectual disability. CONCLUSION Supine sleep is likely a physiological stressor, that does reduce SIDS, but at the cost of impact on emotional and social development in the population, a portion of which will be susceptible to, and consequently express autism. A re-evaluation of all benefits and harms of supine sleep is warranted. If the SIDS mechanism proposed and autism model presented can be verified, the research agenda may be better directed, in order to further decrease SIDS, and reduce autism incidence. PMID:27610351

PI(4,5)P2-binding effector proteins for vesicle exocytosis

PubMed Central

Martin, Thomas F. J.

2014-01-01

PI(4,5)P2 participates directly in priming and possibly fusion steps of Ca2+-triggered vesicle exocytosis. High concentration nanodomains of PI(4,5)P2 reside on the plasma membrane of neuroendocrine cells. A subset of vesicles that co-localize with PI(4,5)P2 domains appear to undergo preferential exocytosis in stimulated cells. PI(4,5)P2 directly regulates vesicle exocytosis by recruiting and activating PI(4,5)P2-binding proteins that regulate SNARE protein function including CAPS, Munc13-1/2, synaptotagmin-1, and other C2 domain-containing proteins. These PI(4,5)P2 effector proteins are coincidence detectors that engage in multiple interactions at vesicle exocytic sites. The SNARE protein syntaxin-1 also binds to PI(4,5)P2, which promotes clustering, but an activating role for PI(4,5)P2 in syntaxin-1 function remains to be fully characterized. Similar principles underlie polarized constitutive vesicle fusion mediated in part by the PI(4,5)P2-binding subunits of the exocyst complex (Sec3, Exo70). Overall, focal vesicle exocytosis occurs at sites landmarked by PI(4,5)P2, which serves to recruit and/or activate multifunctional PI(4,5)P2-binding proteins. PMID:25280637

Are the World's Oceans Optically Different?

NASA Technical Reports Server (NTRS)

Szeto, M.; Werdell, P. J.; Moore, T. S.; Campbell, J. W.

2011-01-01

Regional differences in the Sea-viewing Wide Field-of-view Sensor chlorophyll algorithm uncertainty were observed in a large global data set containing coincident in situ measurements of chlorophyll a concentration (Chla) and spectral radiometry. The uncertainty was found to be systematic when the data were sorted by ocean: Atlantic, Pacific, Southern, and Indian Oceans. Artifacts associated with different instrumentation and analytical methods had been previously ruled out. Given these oceanic biases in the chlorophyll algorithm, we hypothesized that the oceans may be optically different, and their optical differences may be intrinsically related to regional differences in phytoplankton community structure or biogeochemical processes. The oceanic biases, originally observed using radiometric measurements, were independently verified using total absorption measurements in a subset of the data. Moreover, they were explained through oceanic differences in the absorption of colored detrital matter (CDM) and phytoplankton. Both effects were considered together in explaining the ocean biases through a stepwise linear regression analysis. Significant oceanic differences in the amount of CDM and in phytoplankton cell sizes and pigmentation would give rise to optical differences, but we raise a concern for the spatial coverage of the data. We do not suggest the application of ocean-based algorithms but rather emphasize the importance of consolidating regional data sets before reaching this conclusion.

Mid-sagittal plane and mid-sagittal surface optimization in brain MRI using a local symmetry measure

NASA Astrophysics Data System (ADS)

Stegmann, Mikkel B.; Skoglund, Karl; Ryberg, Charlotte

2005-04-01

This paper describes methods for automatic localization of the mid-sagittal plane (MSP) and mid-sagittal surface (MSS). The data used is a subset of the Leukoaraiosis And DISability (LADIS) study consisting of three-dimensional magnetic resonance brain data from 62 elderly subjects (age 66 to 84 years). Traditionally, the mid-sagittal plane is localized by global measures. However, this approach fails when the partitioning plane between the brain hemispheres does not coincide with the symmetry plane of the head. We instead propose to use a sparse set of profiles in the plane normal direction and maximize the local symmetry around these using a general-purpose optimizer. The plane is parameterized by azimuth and elevation angles along with the distance to the origin in the normal direction. This approach leads to solutions confirmed as the optimal MSP in 98 percent of the subjects. Despite the name, the mid-sagittal plane is not always planar, but a curved surface resulting in poor partitioning of the brain hemispheres. To account for this, this paper also investigates an optimization strategy which fits a thin-plate spline surface to the brain data using a robust least median of squares estimator. Albeit computationally more expensive, mid-sagittal surface fitting demonstrated convincingly better partitioning of curved brains into cerebral hemispheres.

Hierarchical clusters in families with type 2 diabetes.

PubMed

García-Solano, Beatriz; Gallegos-Cabriales, Esther C; Gómez-Meza, Marco V; García-Madrid, Guillermina; Flores-Merlo, Marcela; García-Solano, Mauro

2015-01-01

Families represent more than a set of individuals; family is more than a sum of its individual members. With this classification, nurses can identify the family health-illness beliefs obey family as a unit concept, and plan family inclusion into the type 2 diabetes treatment, whom is not considered in public policy, despite families share diet, exercise, and self-monitoring with a member who suffers type 2 diabetes. The aim of this study was to determine whether the characteristics, functionality, routines, and family and individual health in type 2 diabetes describes the differences and similarities between families to consider them as a unit. We performed an exploratory, descriptive hierarchical cluster analysis of 61 families using three instruments and a questionnaire, in addition to weight, height, body fat percentage, hemoglobin A1c, total cholesterol, triglycerides, low-density lipoprotein and high-density lipoprotein. The analysis produced three groups of families. Wilk's lambda demonstrated statistically significant differences provided by age (Λ = 0.778, F = 2.098, p = 0.010) and family health (Λ = 0.813, F = 2.650, p = 0.023). A post hoc Tukey test coincided with the three subsets. Families with type 2 diabetes have common elements that make them similar, while sharing differences that make them unique.

Moments of the Particle Phase-Space Density at Freeze-out and Coincidence Probabilities

NASA Astrophysics Data System (ADS)

Bialas, A.; Czyż, W.; Zalewski, K.

2005-10-01

It is pointed out that the moments of phase-space particle density at freeze-out can be determined from the coincidence probabilities of the events observed in multiparticle production. A method to measure the coincidence probabilities is described and its validity examined.

Three-dimensional ordered-subset expectation maximization iterative protocol for evaluation of left ventricular volumes and function by quantitative gated SPECT: a dynamic phantom study.

PubMed

Ceriani, Luca; Ruberto, Teresa; Delaloye, Angelika Bischof; Prior, John O; Giovanella, Luca

2010-03-01

The purposes of this study were to characterize the performance of a 3-dimensional (3D) ordered-subset expectation maximization (OSEM) algorithm in the quantification of left ventricular (LV) function with (99m)Tc-labeled agent gated SPECT (G-SPECT), the QGS program, and a beating-heart phantom and to optimize the reconstruction parameters for clinical applications. A G-SPECT image of a dynamic heart phantom simulating the beating left ventricle was acquired. The exact volumes of the phantom were known and were as follows: end-diastolic volume (EDV) of 112 mL, end-systolic volume (ESV) of 37 mL, and stroke volume (SV) of 75 mL; these volumes produced an LV ejection fraction (LVEF) of 67%. Tomographic reconstructions were obtained after 10-20 iterations (I) with 4, 8, and 16 subsets (S) at full width at half maximum (FWHM) gaussian postprocessing filter cutoff values of 8-15 mm. The QGS program was used for quantitative measurements. Measured values ranged from 72 to 92 mL for EDV, from 18 to 32 mL for ESV, and from 54 to 63 mL for SV, and the calculated LVEF ranged from 65% to 76%. Overall, the combination of 10 I, 8 S, and a cutoff filter value of 10 mm produced the most accurate results. The plot of the measures with respect to the expectation maximization-equivalent iterations (I x S product) revealed a bell-shaped curve for the LV volumes and a reverse distribution for the LVEF, with the best results in the intermediate range. In particular, FWHM cutoff values exceeding 10 mm affected the estimation of the LV volumes. The QGS program is able to correctly calculate the LVEF when used in association with an optimized 3D OSEM algorithm (8 S, 10 I, and FWHM of 10 mm) but underestimates the LV volumes. However, various combinations of technical parameters, including a limited range of I and S (80-160 expectation maximization-equivalent iterations) and low cutoff values (< or =10 mm) for the gaussian postprocessing filter, produced results with similar accuracies and without clinically relevant differences in the LV volumes and the estimated LVEF.

Redefining Myeloid Cell Subsets in Murine Spleen

PubMed Central

Hey, Ying-Ying; Tan, Jonathan K. H.; O’Neill, Helen C.

2016-01-01

Spleen is known to contain multiple dendritic and myeloid cell subsets, distinguishable on the basis of phenotype, function and anatomical location. As a result of recent intensive flow cytometric analyses, splenic dendritic cell (DC) subsets are now better characterized than other myeloid subsets. In order to identify and fully characterize a novel splenic subset termed “L-DC” in relation to other myeloid cells, it was necessary to investigate myeloid subsets in more detail. In terms of cell surface phenotype, L-DC were initially characterized as a CD11bhiCD11cloMHCII−Ly6C−Ly6G− subset in murine spleen. Their expression of CD43, lack of MHCII, and a low level of CD11c was shown to best differentiate L-DC by phenotype from conventional DC subsets. A complete analysis of all subsets in spleen led to the classification of CD11bhiCD11cloMHCII−Ly6CloLy6G− cells as monocytes expressing CX3CR1, CD43 and CD115. Siglec-F expression was used to identify a specific eosinophil population, distinguishable from both Ly6Clo and Ly6Chi monocytes, and other DC subsets. L-DC were characterized as a clear subset of CD11bhiCD11cloMHCII−Ly6C−Ly6G− cells, which are CD43+, Siglec-F− and CD115−. Changes in the prevalence of L-DC compared to other subsets in spleens of mutant mice confirmed the phenotypic distinction between L-DC, cDC and monocyte subsets. L-DC development in vivo was shown to occur independently of the BATF3 transcription factor that regulates cDC development, and also independently of the FLT3L and GM-CSF growth factors which drive cDC and monocyte development, so distinguishing L-DC from these commonly defined cell types. PMID:26793192

From Mere Coincidences to Meaningful Discoveries

ERIC Educational Resources Information Center

Griffiths, Thomas L.; Tenenbaum, Joshua B.

2007-01-01

People's reactions to coincidences are often cited as an illustration of the irrationality of human reasoning about chance. We argue that coincidences may be better understood in terms of rational statistical inference, based on their functional role in processes of causal discovery and theory revision. We present a formal definition of…

A data acquisition system for coincidence imaging using a conventional dual head gamma camera

NASA Astrophysics Data System (ADS)

Lewellen, T. K.; Miyaoka, R. S.; Jansen, F.; Kaplan, M. S.

1997-06-01

A low cost data acquisition system (DAS) was developed to acquire coincidence data from an unmodified General Electric Maxxus dual head scintillation camera. A high impedance pick-off circuit provides position and energy signals to the DAS without interfering with normal camera operation. The signals are pulse-clipped to reduce pileup effects. Coincidence is determined with fast timing signals derived from constant fraction discriminators. A charge-integrating FERA 16 channel ADC feeds position and energy data to two CAMAC FERA memories operated as ping-pong buffers. A Macintosh PowerPC running Labview controls the system and reads the CAMAC memories. A CAMAC 12-channel scaler records singles and coincidence rate data. The system dead-time is approximately 10% at a coincidence rate of 4.0 kHz.

Monocyte Subset Dynamics in Human Atherosclerosis Can Be Profiled with Magnetic Nano-Sensors

PubMed Central

Wildgruber, Moritz; Lee, Hakho; Chudnovskiy, Aleksey; Yoon, Tae-Jong; Etzrodt, Martin; Pittet, Mikael J.; Nahrendorf, Matthias; Croce, Kevin; Libby, Peter; Weissleder, Ralph; Swirski, Filip K.

2009-01-01

Monocytes are circulating macrophage and dendritic cell precursors that populate healthy and diseased tissue. In humans, monocytes consist of at least two subsets whose proportions in the blood fluctuate in response to coronary artery disease, sepsis, and viral infection. Animal studies have shown that specific shifts in the monocyte subset repertoire either exacerbate or attenuate disease, suggesting a role for monocyte subsets as biomarkers and therapeutic targets. Assays are therefore needed that can selectively and rapidly enumerate monocytes and their subsets. This study shows that two major human monocyte subsets express similar levels of the receptor for macrophage colony stimulating factor (MCSFR) but differ in their phagocytic capacity. We exploit these properties and custom-engineer magnetic nanoparticles for ex vivo sensing of monocytes and their subsets. We present a two-dimensional enumerative mathematical model that simultaneously reports number and proportion of monocyte subsets in a small volume of human blood. Using a recently described diagnostic magnetic resonance (DMR) chip with 1 µl sample size and high throughput capabilities, we then show that application of the model accurately quantifies subset fluctuations that occur in patients with atherosclerosis. PMID:19461894

Dynamic equilibrium of heterogeneous and interconvertible multipotent hematopoietic cell subsets

PubMed Central

Weston, Wendy; Zayas, Jennifer; Perez, Ruben; George, John; Jurecic, Roland

2014-01-01

Populations of hematopoietic stem cells and progenitors are quite heterogeneous and consist of multiple cell subsets with distinct phenotypic and functional characteristics. Some of these subsets also appear to be interconvertible and oscillate between functionally distinct states. The multipotent hematopoietic cell line EML has emerged as a unique model to study the heterogeneity and interconvertibility of multipotent hematopoietic cells. Here we describe extensive phenotypic and functional heterogeneity of EML cells which stems from the coexistence of multiple cell subsets. Each of these subsets is phenotypically and functionally heterogeneous, and displays distinct multilineage differentiation potential, cell cycle profile, proliferation kinetics, and expression pattern of HSC markers and some of the key lineage-associated transcription factors. Analysis of their maintenance revealed that on a population level all EML cell subsets exhibit cell-autonomous interconvertible properties, with the capacity to generate all other subsets and re-establish complete parental EML cell population. Moreover, all EML cell subsets generated during multiple cell generations maintain their distinct phenotypic and functional signatures and interconvertible properties. The model of EML cell line suggests that interconvertible multipotent hematopoietic cell subsets coexist in a homeostatically maintained dynamic equilibrium which is regulated by currently unknown cell-intrinsic mechanisms. PMID:24903657

Dynamic equilibrium of heterogeneous and interconvertible multipotent hematopoietic cell subsets.

PubMed

Weston, Wendy; Zayas, Jennifer; Perez, Ruben; George, John; Jurecic, Roland

2014-06-06

Populations of hematopoietic stem cells and progenitors are quite heterogeneous and consist of multiple cell subsets with distinct phenotypic and functional characteristics. Some of these subsets also appear to be interconvertible and oscillate between functionally distinct states. The multipotent hematopoietic cell line EML has emerged as a unique model to study the heterogeneity and interconvertibility of multipotent hematopoietic cells. Here we describe extensive phenotypic and functional heterogeneity of EML cells which stems from the coexistence of multiple cell subsets. Each of these subsets is phenotypically and functionally heterogeneous, and displays distinct multilineage differentiation potential, cell cycle profile, proliferation kinetics, and expression pattern of HSC markers and some of the key lineage-associated transcription factors. Analysis of their maintenance revealed that on a population level all EML cell subsets exhibit cell-autonomous interconvertible properties, with the capacity to generate all other subsets and re-establish complete parental EML cell population. Moreover, all EML cell subsets generated during multiple cell generations maintain their distinct phenotypic and functional signatures and interconvertible properties. The model of EML cell line suggests that interconvertible multipotent hematopoietic cell subsets coexist in a homeostatically maintained dynamic equilibrium which is regulated by currently unknown cell-intrinsic mechanisms.

Data-driven confounder selection via Markov and Bayesian networks.

PubMed

Häggström, Jenny

2018-06-01

To unbiasedly estimate a causal effect on an outcome unconfoundedness is often assumed. If there is sufficient knowledge on the underlying causal structure then existing confounder selection criteria can be used to select subsets of the observed pretreatment covariates, X, sufficient for unconfoundedness, if such subsets exist. Here, estimation of these target subsets is considered when the underlying causal structure is unknown. The proposed method is to model the causal structure by a probabilistic graphical model, for example, a Markov or Bayesian network, estimate this graph from observed data and select the target subsets given the estimated graph. The approach is evaluated by simulation both in a high-dimensional setting where unconfoundedness holds given X and in a setting where unconfoundedness only holds given subsets of X. Several common target subsets are investigated and the selected subsets are compared with respect to accuracy in estimating the average causal effect. The proposed method is implemented with existing software that can easily handle high-dimensional data, in terms of large samples and large number of covariates. The results from the simulation study show that, if unconfoundedness holds given X, this approach is very successful in selecting the target subsets, outperforming alternative approaches based on random forests and LASSO, and that the subset estimating the target subset containing all causes of outcome yields smallest MSE in the average causal effect estimation. © 2017, The International Biometric Society.

Capturing the systemic immune signature of a norovirus infection: an n-of-1 case study within a clinical trial

PubMed Central

Cutler, Antony J.; Oliveira, Joao; Ferreira, Ricardo C.; Challis, Ben; Walker, Neil M.; Caddy, Sarah; Lu, Jia; Stevens, Helen E.; Smyth, Deborah J.; Pekalski, Marcin L.; Kennet, Jane; Hunter, Kara M.D.; Goodfellow, Ian; Wicker, Linda S.; Todd, John A.; Waldron-Lynch, Frank

2017-01-01

Background: The infection of a participant with norovirus during the adaptive study of interleukin-2 dose on regulatory T cells in type 1 diabetes (DILT1D) allowed a detailed insight into the cellular and cytokine immune responses to this prevalent gastrointestinal pathogen. Methods:  Serial blood, serum and peripheral blood mononuclear cell (PBMC) samples were collected pre-, and post-development of the infection. To differentiate between the immune response to norovirus and to control for the administration of a single dose of aldesleukin (recombinant interleukin-2, rIL-2) alone, samples from five non-infected participants administered similar doses were analysed in parallel. Results: Norovirus infection was self-limited and resolved within 24 hours, with the subsequent development of anti-norovirus antibodies. Serum pro- and anti-inflammatory cytokine levels, including IL-10, peaked during the symptomatic period of infection, coincident with increased frequencies of monocytes and neutrophils. At the same time, the frequency of regulatory CD4 + T cell (Treg), effector T cell (Teff) CD4 + and CD8 + subsets were dynamically reduced, rebounding to baseline levels or above at the next sampling point 24 hours later.  NK cells and NKT cells transiently increased CD69 expression and classical monocytes expressed increased levels of CD40, HLA-DR and SIGLEC-1, biomarkers of an interferon response. We also observed activation and mobilisation of Teffs, where increased frequencies of CD69 + and Ki-67 + effector memory Teffs were followed by the emergence of memory CD8 + Teff expressing the mucosal tissue homing markers CD103 and β7 integrin. Treg responses were coincident with the innate cell, Teff and cytokine response. Key Treg molecules FOXP3, CTLA-4, and CD25 were upregulated following infection, alongside an increase in frequency of Tregs with the capacity to home to tissues. Conclusions:  The results illustrate the innate, adaptive and counter-regulatory immune responses to norovirus infection. Low-dose IL-2 administration induces many of the Treg responses observed during infection. PMID:28815218

Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

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

Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.

Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at differentmore » developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner. • The nicotine-induced secondary motoneuron axonal pathfinding errors can occur independent of any muscle fiber alterations. • Nicotine exposure primarily affects dorsal projecting secondary motoneurons axons. • Nicotine-induced primary motoneuron axon pathfinding errors can influence secondary motoneuron axon morphology.« less

On the performance of tests for the detection of signatures of selection: a case study with the Spanish autochthonous beef cattle populations.

PubMed

González-Rodríguez, Aldemar; Munilla, Sebastián; Mouresan, Elena F; Cañas-Álvarez, Jhon J; Díaz, Clara; Piedrafita, Jesús; Altarriba, Juan; Baro, Jesús Á; Molina, Antonio; Varona, Luis

2016-10-28

Procedures for the detection of signatures of selection can be classified according to the source of information they use to reject the null hypothesis of absence of selection. Three main groups of tests can be identified that are based on: (1) the analysis of the site frequency spectrum, (2) the study of the extension of the linkage disequilibrium across the length of the haplotypes that surround the polymorphism, and (3) the differentiation among populations. The aim of this study was to compare the performance of a subset of these procedures by using a dataset on seven Spanish autochthonous beef cattle populations. Analysis of the correlations between the logarithms of the statistics that were obtained by 11 tests for detecting signatures of selection at each single nucleotide polymorphism confirmed that they can be clustered into the three main groups mentioned above. A factor analysis summarized the results of the 11 tests into three canonical axes that were each associated with one of the three groups. Moreover, the signatures of selection identified with the first and second groups of tests were shared across populations, whereas those with the third group were more breed-specific. Nevertheless, an enrichment analysis identified the metabolic pathways that were associated with each group; they coincided with canonical axes and were related to immune response, muscle development, protein biosynthesis, skin and pigmentation, glucose metabolism, fat metabolism, embryogenesis and morphology, heart and uterine metabolism, regulation of the hypothalamic-pituitary-thyroid axis, hormonal, cellular cycle, cell signaling and extracellular receptors. We show that the results of the procedures used to identify signals of selection differed substantially between the three groups of tests. However, they can be classified using a factor analysis. Moreover, each canonical factor that coincided with a group of tests identified different signals of selection, which could be attributed to processes of selection that occurred at different evolutionary times. Nevertheless, the metabolic pathways that were associated with each group of tests were similar, which suggests that the selection events that occurred during the evolutionary history of the populations probably affected the same group of traits.

Gamma-gamma coincidence performance of LaBr 3:Ce scintillation detectors vs HPGe detectors in high count-rate scenarios

DOE PAGES

Drescher, A.; Yoho, M.; Landsberger, S.; ...

2017-01-15

In this study, a radiation detection system consisting of two cerium doped lanthanum bromide (LaBr 3:Ce) scintillation detectors in a gamma-gamma coincidence configuration has been used to demonstrate the advantages that coincident detection provides relative to a single detector, and the advantages that LaBr 3:Ce detectors provide relative to high purity germanium (HPGe) detectors. Signal to noise ratios of select photopeak pairs for these detectors have been compared to high-purity germanium (HPGe) detectors in both single and coincident detector configurations in order to quantify the performance of each detector configuration. The efficiency and energy resolution of LaBr 3:Ce detectors havemore » been determined and compared to HPGe detectors. Coincident gamma-ray pairs from the radionuclides 152Eu and 133Ba have been identified in a sample that is dominated by 137Cs. Gamma-gamma coincidence successfully reduced the Compton continuum from the large 137Cs peak, revealed several coincident gamma energies characteristic of these nuclides, and improved the signal-to-noise ratio relative to single detector measurements. LaBr 3:Ce detectors performed at count rates multiple times higher than can be achieved with HPGe detectors. The standard background spectrum consisting of peaks associated with transitions within the LaBr 3:Ce crystal has also been significantly reduced. Finally, it is shown that LaBr 3:Ce detectors have the unique capability to perform gamma-gamma coincidence measurements in very high count rate scenarios, which can potentially benefit nuclear safeguards in situ measurements of spent nuclear fuel.« less

Gamma-gamma coincidence performance of LaBr 3:Ce scintillation detectors vs HPGe detectors in high count-rate scenarios

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

Drescher, A.; Yoho, M.; Landsberger, S.

In this study, a radiation detection system consisting of two cerium doped lanthanum bromide (LaBr 3:Ce) scintillation detectors in a gamma-gamma coincidence configuration has been used to demonstrate the advantages that coincident detection provides relative to a single detector, and the advantages that LaBr 3:Ce detectors provide relative to high purity germanium (HPGe) detectors. Signal to noise ratios of select photopeak pairs for these detectors have been compared to high-purity germanium (HPGe) detectors in both single and coincident detector configurations in order to quantify the performance of each detector configuration. The efficiency and energy resolution of LaBr 3:Ce detectors havemore » been determined and compared to HPGe detectors. Coincident gamma-ray pairs from the radionuclides 152Eu and 133Ba have been identified in a sample that is dominated by 137Cs. Gamma-gamma coincidence successfully reduced the Compton continuum from the large 137Cs peak, revealed several coincident gamma energies characteristic of these nuclides, and improved the signal-to-noise ratio relative to single detector measurements. LaBr 3:Ce detectors performed at count rates multiple times higher than can be achieved with HPGe detectors. The standard background spectrum consisting of peaks associated with transitions within the LaBr 3:Ce crystal has also been significantly reduced. Finally, it is shown that LaBr 3:Ce detectors have the unique capability to perform gamma-gamma coincidence measurements in very high count rate scenarios, which can potentially benefit nuclear safeguards in situ measurements of spent nuclear fuel.« less

Coincidence measurements in α/β/γ spectrometry with phoswich detectors using digital pulse shape discrimination analysis

NASA Astrophysics Data System (ADS)

de Celis, B.; de la Fuente, R.; Williart, A.; de Celis Alonso, B.

2007-09-01

A novel system has been developed for the detection of low radioactivity levels using coincidence techniques. The device combines a phoswich detector for α/β/γ ray recognition with a fast digital card for electronic pulse analysis. The detector is able to discriminate different types of radiation in a mixed α/β/γ field and can be used in a coincidence mode by identifying the composite signal produced by the simultaneous detection of β particles in a plastic scintillator and γ rays in an NaI(Tl) scintillator. Use of a coincidence technique with phoswich detectors was proposed recently to verify the Nuclear Test Ban Treaty, which made it necessary to monitor the low levels of xenon radioisotopes produced by underground nuclear explosions. Previous studies have shown that combining CaF 2(Eu) for β ray detection and NaI(Tl) for γ ray detection makes it difficult to identify the coincidence signals because of the similar fluorescence decay times of the two scintillators. With the device proposed here, it is possible to identify the coincidence events owing to the short fluorescence decay time of the plastic scintillator. The sensitivity of the detector may be improved by employing liquid scintillators, which allow low radioactivity levels from actinides to be measured when present in environmental samples. The device developed is simpler to use than conventional coincidence equipment because it uses a single detector and electronic circuit, and it offers fast and precise analysis of the coincidence signals by employing digital pulse shape analysis.

The Tree-Ring Mercury Record of Gold Mining in the Klondike, Central Yukon Territory

NASA Astrophysics Data System (ADS)

Clackett, S.; Porter, T. J.; Lehnherr, I.

2016-12-01

Mercury (Hg) is an atmospherically mixed pollutant of global concern with the potential to become toxic methyl-Hg (MeHg) is some environments. Accurate projections of future health impacts caused by Hg pollution will partly depend on changes in the atmospheric Hg pool, but knowledge of natural Hg variability is limited by a lack of long term monitoring data, which precludes a robust analysis of how it may evolve in the future. Natural archives such as lake sediments, ice cores and tree-rings have the potential to fill this knowledge gap. Tree-rings may be ideally suited for this purpose since they are annually resolved, they span multiple centuries in some areas, and cover large portions of the Earth's surface. Few studies have evaluated tree-ring Hg, and generally agree tree-rings are a passive archive for local Hg emissions. However, further studies are needed to validate this hypothesis. An ideal site to test this proxy is Bear Creek in the Klondike where the Hg amalgamation method was used during the period 1918-1966 to recover fine gold from placer ore. Gaseous Hg was lost to the local environment during operations, as is confirmed by high soil Hg concentrations at the site today. Local trees would have been exposed to the elevated Hg emissions. We measured tree-ring Hg at Bear Creek to determine if historical Hg trends are preserved. Our preliminary results from a single tree reveal that: (1) peak tree-ring Hg coincides with Bear Creek operations; (2) the lowest tree-ring Hg is observed during the pre-industrial control period (1870-1880); and (3) post-Bear Creek operations (1970-2010) coincides with intermediate tree-ring Hg levels, presumably due to higher Hg global backgrounds in recent decades. Additional trees are being analysed to determine if this result is robust, and will provide important insights on the reliability of this proxy for reconstructing long-term atmospheric Hg at local and potentially broader spatial scales.

Evolution of the PEBP gene family in plants: functional diversification in seed plant evolution.

PubMed

Karlgren, Anna; Gyllenstrand, Niclas; Källman, Thomas; Sundström, Jens F; Moore, David; Lascoux, Martin; Lagercrantz, Ulf

2011-08-01

The phosphatidyl ethanolamine-binding protein (PEBP) gene family is present in all eukaryote kingdoms, with three subfamilies identified in angiosperms (FLOWERING LOCUS T [FT], MOTHER OF FT AND TFL1 [MFT], and TERMINAL FLOWER1 [TFL1] like). In angiosperms, PEBP genes have been shown to function both as promoters and suppressors of flowering and to control plant architecture. In this study, we focus on previously uncharacterized PEBP genes from gymnosperms. Extensive database searches suggest that gymnosperms possess only two types of PEBP genes, MFT-like and a group that occupies an intermediate phylogenetic position between the FT-like and TFL1-like (FT/TFL1-like). Overexpression of Picea abies PEBP genes in Arabidopsis (Arabidopsis thaliana) suggests that the FT/TFL1-like genes (PaFTL1 and PaFTL2) code for proteins with a TFL1-like function. However, PaFTL1 and PaFTL2 also show highly divergent expression patterns. While the expression of PaFTL2 is correlated with annual growth rhythm and mainly confined to needles and vegetative and reproductive buds, the expression of PaFTL1 is largely restricted to microsporophylls of male cones. The P. abies MFT-like genes (PaMFT1 and PaMFT2) show a predominant expression during embryo development, a pattern that is also found for many MFT-like genes from angiosperms. P. abies PEBP gene expression is primarily detected in tissues undergoing physiological changes related to growth arrest and dormancy. A first duplication event resulting in two families of plant PEBP genes (MFT-like and FT/TFL1-like) seems to coincide with the evolution of seed plants, in which independent control of bud and seed dormancy was required, and the second duplication resulting in the FT-like and TFL1-like clades probably coincided with the evolution of angiosperms.

Population dynamics and habitat sharing of natural populations of Caenorhabditis elegans and C. briggsae

PubMed Central

2012-01-01

Background The nematode Caenorhabditis elegans is a major model organism in laboratory biology. Very little is known, however, about its ecology, including where it proliferates. In the past, C. elegans was mainly isolated from human-made compost heaps, where it was overwhelmingly found in the non-feeding dauer diapause stage. Results C. elegans and C. briggsae were found in large, proliferating populations in rotting plant material (fruits and stems) in several locations in mainland France. Both species were found to co-occur in samples isolated from a given plant species. Population counts spanned a range from one to more than 10,000 Caenorhabditis individuals on a single fruit or stem. Some populations with an intermediate census size (10 to 1,000) contained no dauer larvae at all, whereas larger populations always included some larvae in the pre-dauer or dauer stages. We report on associated micro-organisms, including pathogens. We systematically sampled a spatio-temporally structured set of rotting apples in an apple orchard in Orsay over four years. C. elegans and C. briggsae were abundantly found every year, but their temporal distributions did not coincide. C. briggsae was found alone in summer, whereas both species co-occurred in early fall and C. elegans was found alone in late fall. Competition experiments in the laboratory at different temperatures show that C. briggsae out-competes C. elegans at high temperatures, whereas C. elegans out-competes C. briggsae at lower temperatures. Conclusions C. elegans and C. briggsae proliferate in the same rotting vegetal substrates. In contrast to previous surveys of populations in compost heaps, we found fully proliferating populations with no dauer larvae. The temporal sharing of the habitat by the two species coincides with their temperature preference in the laboratory, with C. briggsae populations growing faster than C. elegans at higher temperatures, and vice at lower temperatures. PMID:22731941

CRF-PEPICO: Double velocity map imaging photoelectron photoion coincidence spectroscopy for reaction kinetics studies

NASA Astrophysics Data System (ADS)

Sztáray, Bálint; Voronova, Krisztina; Torma, Krisztián G.; Covert, Kyle J.; Bodi, Andras; Hemberger, Patrick; Gerber, Thomas; Osborn, David L.

2017-07-01

Photoelectron photoion coincidence (PEPICO) spectroscopy could become a powerful tool for the time-resolved study of multi-channel gas phase chemical reactions. Toward this goal, we have designed and tested electron and ion optics that form the core of a new PEPICO spectrometer, utilizing simultaneous velocity map imaging for both cations and electrons, while also achieving good cation mass resolution through space focusing. These optics are combined with a side-sampled, slow-flow chemical reactor for photolytic initiation of gas-phase chemical reactions. Together with a recent advance that dramatically increases the dynamic range in PEPICO spectroscopy [D. L. Osborn et al., J. Chem. Phys. 145, 164202 (2016)], the design described here demonstrates a complete prototype spectrometer and reactor interface to carry out time-resolved experiments. Combining dual velocity map imaging with cation space focusing yields tightly focused photoion images for translationally cold neutrals, while offering good mass resolution for thermal samples as well. The flexible optics design incorporates linear electric fields in the ionization region, surrounded by dual curved electric fields for velocity map imaging of ions and electrons. Furthermore, the design allows for a long extraction stage, which makes this the first PEPICO experiment to combine ion imaging with the unimolecular dissociation rate constant measurements of cations to detect and account for kinetic shifts. Four examples are shown to illustrate some capabilities of this new design. We recorded the threshold photoelectron spectrum of the propargyl and the iodomethyl radicals. While the former agrees well with a literature threshold photoelectron spectrum, we have succeeded in resolving the previously unobserved vibrational structure in the latter. We have also measured the bimolecular rate constant of the CH2I + O2 reaction and observed its product, the smallest Criegee intermediate, CH2OO. Finally, the second dissociative photoionization step of iodocyclohexane ions, the loss of ethylene from the cyclohexyl cation, is slow at threshold, as illustrated by the asymmetric threshold photoionization time-of-flight distributions.

Extensive theoretical/numerical comparative studies on H2 and generalised H2 norms in sampled-data systems

NASA Astrophysics Data System (ADS)

Kim, Jung Hoon; Hagiwara, Tomomichi

2017-11-01

This paper is concerned with linear time-invariant (LTI) sampled-data systems (by which we mean sampled-data systems with LTI generalised plants and LTI controllers) and studies their H2 norms from the viewpoint of impulse responses and generalised H2 norms from the viewpoint of the induced norms from L2 to L∞. A new definition of the H2 norm of LTI sampled-data systems is first introduced through a sort of intermediate standpoint of those for the existing two definitions. We then establish unified treatment of the three definitions of the H2 norm through a matrix function G(τ) defined on the sampling interval [0, h). This paper next considers the generalised H2 norms, in which two types of the L∞ norm of the output are considered as the temporal supremum magnitude under the spatial 2-norm and ∞-norm of a vector-valued function. We further give unified treatment of the generalised H2 norms through another matrix function F(θ) which is also defined on [0, h). Through a close connection between G(τ) and F(θ), some theoretical relationships between the H2 and generalised H2 norms are provided. Furthermore, appropriate extensions associated with the treatment of G(τ) and F(θ) to the closed interval [0, h] are discussed to facilitate numerical computations and comparisons of the H2 and generalised H2 norms. Through theoretical and numerical studies, it is shown that the two generalised H2 norms coincide with neither of the three H2 norms of LTI sampled-data systems even though all the five definitions coincide with each other when single-output continuous-time LTI systems are considered as a special class of LTI sampled-data systems. To summarise, this paper clarifies that the five control performance measures are mutually related with each other but they are also intrinsically different from each other.

Development of an Apparatus for High-Resolution Auger Photoelectron Coincidence Spectroscopy (APECS) and Electron Ion Coincidence (EICO) Spectroscopy

NASA Astrophysics Data System (ADS)

Kakiuchi, Takuhiro; Hashimoto, Shogo; Fujita, Narihiko; Mase, Kazuhiko; Tanaka, Masatoshi; Okusawa, Makoto

We have developed an electron electron ion coincidence (EEICO) apparatus for high-resolution Auger photoelectron coincidence spectroscopy (APECS) and electron ion coincidence (EICO) spectroscopy. It consists of a coaxially symmetric mirror electron energy analyzer (ASMA), a miniature double-pass cylindrical mirror electron energy analyzer (DP-CMA), a miniature time-of-flight ion mass spectrometer (TOF-MS), a magnetic shield, an xyz stage, a tilt-adjustment mechanism, and a conflat flange with an outer diameter of 203 mm. A sample surface was irradiated by synchrotron radiation, and emitted electrons were energy-analyzed and detected by the ASMA and the DP-CMA, while desorbed ions were mass-analyzed and detected by the TOF-MS. The performance of the new EEICO analyzer was evaluated by measuring Si 2p photoelectron spectra of clean Si(001)-2×1 and Si(111)-7×7, and by measuring Si-L23VV-Si-2p Auger photoelectron coincidence spectra (Si-L23VV-Si-2p APECS) of clean Si(001)-2×1.

A scalable multi-photon coincidence detector based on superconducting nanowires.

PubMed

Zhu, Di; Zhao, Qing-Yuan; Choi, Hyeongrak; Lu, Tsung-Ju; Dane, Andrew E; Englund, Dirk; Berggren, Karl K

2018-06-04

Coincidence detection of single photons is crucial in numerous quantum technologies and usually requires multiple time-resolved single-photon detectors. However, the electronic readout becomes a major challenge when the measurement basis scales to large numbers of spatial modes. Here, we address this problem by introducing a two-terminal coincidence detector that enables scalable readout of an array of detector segments based on superconducting nanowire microstrip transmission line. Exploiting timing logic, we demonstrate a sixteen-element detector that resolves all 136 possible single-photon and two-photon coincidence events. We further explore the pulse shapes of the detector output and resolve up to four-photon events in a four-element device, giving the detector photon-number-resolving capability. This new detector architecture and operating scheme will be particularly useful for multi-photon coincidence detection in large-scale photonic integrated circuits.

Outcome Analysis of Patients With Oral Cavity Cancer and Extracapsular Spread in Neck Lymph Nodes

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

Liao, Chun-Ta, E-mail: liaoct@adm.cgmh.org.tw; Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Lee, Li-Yu

Purpose: Extracapsular spread (ECS) in neck lymph nodes is a major adverse prognostic factor in patients with oral cavity squamous cell carcinoma (OSCC). We conducted a retrospective analysis of prognostic factors in this patient group and tried to identify a subset of patients with a worse prognosis suitable for more aggressive therapeutic interventions. Methods and Materials: Enrolled in the study were 255 OSCC patients with ECS in neck nodes and without evidence of distant metastasis. All participants were followed-up for at least 2 years or censored at last follow-up. The 5-year rates of control, distant metastasis, and survival were themore » main outcome measures. Results: Level IV/V lymph node metastases and tumor depth {>=}12 mm were independent predictors of 5-year survival and identified three prognostic groups. In the low-risk group (no level IV/V metastases and tumor depth <12 mm), the 5-year disease-free, disease-specific, and overall survival rates were 60%, 66%, and 50%, respectively. In the intermediate-risk group (no level IV/V metastases and tumor depth {>=}12 mm), the 5-year disease-free, disease-specific, and overall survival rates were 39%, 41%, and 28%, respectively. In the high-risk group (evidence of level IV/V metastases), the 5-year disease-free, disease-specific, and overall survival rates were 14%, 12%, and 10%, respectively. Conclusions: Among OSCC patients with ECS, those with level IV/V metastases appear to have the worst prognosis followed by without level IV/V metastases and tumor depth {>=}12 mm. An aggressive therapeutic approach may be suitable for intermediate- and high-risk patients.« less

Tumor development in murine ulcerative colitis depends on MyD88 signaling of colonic F4/80+CD11bhighGr1low macrophages

PubMed Central

Schiechl, Gabriela; Bauer, Bernhard; Fuss, Ivan; Lang, Sven A.; Moser, Christian; Ruemmele, Petra; Rose-John, Stefan; Neurath, Markus F.; Geissler, Edward K.; Schlitt, Hans-Jürgen; Strober, Warren; Fichtner-Feigl, Stefan

2011-01-01

Patients with prolonged ulcerative colitis (UC) frequently develop colorectal adenocarcinoma for reasons that are not fully clear. To analyze inflammation-associated colonic tumorigenesis, we developed a chronic form of oxazolone-induced colitis in mice that, similar to UC, was distinguished by the presence of IL-13–producing NKT cells. In this model, the induction of tumors using azoxymethane was accompanied by the coappearance of F4/80+CD11bhighGr1low M2 macrophages, cells that undergo polarization by IL-13 and are absent in tumors that lack high level IL-13 production. Importantly, this subset of macrophages was a source of tumor-promoting factors, including IL-6. Similar to dextran sodium sulfate–induced colitis, F4/80+CD11bhighGr1intermediate macrophages were present in the mouse model of chronic oxazolone-induced colitis and may influence tumor development through production of TGF-β1, a cytokine that inhibits tumor immunosurveillance. Finally, while robust chronic oxazolone-induced colitis developed in myeloid differentiation primary response gene 88–deficient (Myd88–/–) mice, these mice did not support tumor development. The inhibition of tumor development in Myd88–/– mice correlated with cessation of IL-6 and TGF-β1 production by M2 and F4/80+CD11bhighGr1intermediate macrophages, respectively, and was reversed by exogenous IL-6. These data show that an UC-like inflammation may facilitate tumor development by providing a milieu favoring development of MyD88-dependent tumor-supporting macrophages. PMID:21519141

Homogeneity of Severe Posttraumatic Stress Disorder Symptom Profiles in Children and Adolescents Across Gender, Age, and Traumatic Experiences Related to 9/11.

PubMed

Guffanti, Guia; Geronazzo-Alman, Lupo; Fan, Bin; Duarte, Cristiane S; Musa, George J; Hoven, Christina W

2016-10-01

Patients with a posttraumatic stress disorder (PTSD) diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV; American Psychiatric Association, 1994) will very likely not share all of the same symptoms, a consequence of the polythetic approach used in the DSM. We examined heterogeneity in the latent structure of PTSD symptoms using data from a previously published sample of 8,236 youth a subset of which had been exposed to the September 11, 2001 attacks (N = 6,670; Hoven et al., 2005). Latent class analysis was applied (a) to PTSD symptoms alone, (b) to symptoms in combination with impairment indicators, and (c) to PTSD symptoms when stratified by age and gender, as well as by empirically defined classes of exposure. We identified 4 symptom classes: no disturbance (49.4%), intermediate disturbance (2 classes; 21.5% and 18.6%, respectively), and severe disturbance (10.5%). These classes varied not only in the severity of symptoms, but also in the configuration of symptoms. We observed a high probability of endorsing both PTSD symptoms and indicators of impairment only in the severe disturbance class. A similar 4-class structure was found when the data were stratified by age, gender, and exposure classes. There were no significant differences as a function of age, gender, or exposure in the presence of severe PTSD. Heterogeneity was observed at intermediate levels of PTSD symptom severity. The specific PTSD symptoms that defined the severe PTSD profile could constitute the pathogenic aspects of a largely invariant and clinically meaningful PTSD syndrome. Copyright © 2016 International Society for Traumatic Stress Studies.

Contribution of classical and emerging risk factors to coronary artery disease in Asian Indians.

PubMed

Shanker, Jayashree; Kakkar, Vijay V

2016-07-01

The merits and demerits of classical risk factors in coronary artery disease (CAD) are widely debated. We analyzed the role of conventional (age, gender, diabetes, hypertension, smoking) and non-conventional risk factors (anthropometrics, fasting blood sugar, atherogenic index of plasma - AIP, family history) in Asian Indians with CAD. Out of 11,164 subjects (4855 affected, 6309 unaffected) enrolled in the Indian Atherosclerosis Research Study (IARS), 269 unaffected individuals with abnormal electrocardiogram and seven underage were excluded. Around 10,888 subjects along with two subsets, including 9888 individuals having family history information and 1616 individuals with intermediate Framingham risk score (FRS), were statistically analyzed using SPSS version 17.0 and R software. A combination of classical risk factors showed good discrimination between affected and unaffected individuals (C>0.85). Hypertension (OR 3.79) or male gender (OR 5.31) showed significant association with CAD when lipids were included or excluded from the predictive model, followed by age, diabetes and smoking. Hypertension and diabetes frequencies were higher in older patients (>55years) while smoking was more prevalent in younger patients (<55years). Family history and AIP provided a modest increase in C index over the classical factors (0.864 to 0.873), with 7.1% net reclassification in the intermediate FRS group. In CAD patients, 4% were classified as high risk by FRS, 52% were classified as having metabolic syndrome with revised criteria and over 90% had a high AIP score. Addition of AIP and family history to conventional risk factors improved risk discrimination in Asian Indians with CAD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Maintenance of Genome Integrity by Mi2 Homologs CHD-3 and LET-418 in Caenorhabditis elegans.

PubMed

Turcotte, Carolyn A; Sloat, Solomon A; Rigothi, Julia A; Rosenkranse, Erika; Northrup, Alexandra L; Andrews, Nicolas P; Checchi, Paula M

2018-03-01

Meiotic recombination depends upon the tightly coordinated regulation of chromosome dynamics and is essential for the production of haploid gametes. Central to this process is the formation and repair of meiotic double-stranded breaks (DSBs), which must take place within the constraints of a specialized chromatin architecture. Here, we demonstrate a role for the nucleosome remodeling and deacetylase (NuRD) complex in orchestrating meiotic chromosome dynamics in Caenorhabditis elegans Our data reveal that the conserved Mi2 homologs Chromodomain helicase DNA-binding protein (CHD-3) and its paralog LET-418 facilitate meiotic progression by ensuring faithful repair of DSBs through homologous recombination. We discovered that loss of either CHD-3 or LET-418 results in elevated p53-dependent germ line apoptosis, which relies on the activation of the conserved checkpoint kinase CHK-1 Consistent with these findings, chd-3 and let-418 mutants produce a reduced number of offspring, indicating a role for Mi2 in forming viable gametes. When Mi2 function is compromised, persisting recombination intermediates are detected in late pachytene nuclei, indicating a failure in the timely repair of DSBs. Intriguingly, our data indicate that in Mi2 mutant germ lines, a subset of DSBs are repaired by nonhomologous end joining, which manifests as chromosomal fusions. We find that meiotic defects are exacerbated in Mi2 mutants lacking CKU-80, as evidenced by increased recombination intermediates, corpses, and defects in chromosomal integrity. Taken together, our findings support a model wherein the C. elegans Mi2 complex maintains genomic integrity through reinforcement of a chromatin landscape suitable for homology-driven repair mechanisms. Copyright © 2018 by the Genetics Society of America.

Genetic and phenotypic differentiation of an Andean intermediate altitude population

PubMed Central

Eichstaedt, Christina A; Antão, Tiago; Cardona, Alexia; Pagani, Luca; Kivisild, Toomas; Mormina, Maru

2015-01-01

Highland populations living permanently under hypobaric hypoxia have been subject of extensive research because of the relevance of their physiological adaptations for the understanding of human health and disease. In this context, what is considered high altitude is a matter of interpretation and while the adaptive processes at high altitude (above 3000 m) are well documented, the effects of moderate altitude (below 3000 m) on the phenotype are less well established. In this study, we compare physiological and anthropometric characteristics as well as genetic variations in two Andean populations: the Calchaquíes (2300 m) and neighboring Collas (3500 m). We compare their phenotype and genotype to the sea-level Wichí population. We measured physiological (heart rate, oxygen saturation, respiration rate, and lung function) as well as anthropometric traits (height, sitting height, weight, forearm, and tibia length). We conducted genome-wide genotyping on a subset of the sample (n = 74) and performed various scans for positive selection. At the phenotypic level (n = 179), increased lung capacity stood out in both Andean groups, whereas a growth reduction in distal limbs was only observed at high altitude. At the genome level, Calchaquíes revealed strong signals around PRKG1, suggesting that the nitric oxide pathway may be a target of selection. PRKG1 was highlighted by one of four selection tests among the top five genes using the population branch statistic. Selection tests results of Collas were reported previously. Overall, our study shows that some phenotypic and genetic differentiation occurs at intermediate altitude in response to moderate lifelong selection pressures. PMID:25948820

The Discriminatory Value of CYP2D6 Genotyping in Predicting the Dextromethorphan/Dextrorphan Phenotype in Women with Breast Cancer

PubMed Central

Trojan, Andreas; Vergopoulos, Athanasios; Breitenstein, Urs; Seifert, Burkhardt; Rageth, Christoph; Joechle, Wolfgang

2012-01-01

Background The growth inhibitory effect of tamoxifen is used for the treatment of breast cancer. Tamoxifen efficacy is mediated by its biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoenzyme, to the active metabolite endoxifen. We investigated the relationship of CYP2D6 genotypes to the metabolism of dextromethorphan (DM), which is frequently used as a surrogate marker for the formation of endoxifen. Methods The CYP2D6 genotype was determined by polymerase chain reaction (PCR) in previously untreated patients with hormone receptor-positive invasive breast cancer considered to receive antihormonal therapy. The DM/dextrorphan (DX) urinary excretion ratios were obtained in a subset of patients by high-pressure liquid chromatography (HPLC)-mediated urine analysis after intake of 25 mg DM. The relationships of genotype and corresponding phenotype were statistically analyzed for association. Results From 151 patients predicted based on their genotype data for the ‘traditional’ CYP2D6 phenotype classes poor, intermediate, extensive and ultrarapid, 83 patients were examined for their DM/DX urinary ratios. The genotype-based poor metabolizer status correlated with the DM/DX ratios, whereas the intermediate, extensive and ultrarapid genotypes could not be distinguished based on their phenotype. Citalopram intake did not significantly influence the phenotype. Conclusions The DM metabolism can be reliably used to assess the CYP2D6 enzyme activity. The correlation with the genotype can be incomplete and the metabolic ratios do not seem to be compromised by citalopram. DM phenotyping may provide a standardized tool to better assess the CYP2D6 metabolic capacity. PMID:22553469

Synthesis and accumulation of aromatic aldehydes in an engineered strain of Escherichia coli.

PubMed

Kunjapur, Aditya M; Tarasova, Yekaterina; Prather, Kristala L J

2014-08-20

Aromatic aldehydes are useful in numerous applications, especially as flavors, fragrances, and pharmaceutical precursors. However, microbial synthesis of aldehydes is hindered by rapid, endogenous, and redundant conversion of aldehydes to their corresponding alcohols. We report the construction of an Escherichia coli K-12 MG1655 strain with reduced aromatic aldehyde reduction (RARE) that serves as a platform for aromatic aldehyde biosynthesis. Six genes with reported activity on the model substrate benzaldehyde were rationally targeted for deletion: three genes that encode aldo-keto reductases and three genes that encode alcohol dehydrogenases. Upon expression of a recombinant carboxylic acid reductase in the RARE strain and addition of benzoate during growth, benzaldehyde remained in the culture after 24 h, with less than 12% conversion of benzaldehyde to benzyl alcohol. Although individual overexpression results demonstrated that all six genes could contribute to benzaldehyde reduction in vivo, additional experiments featuring subset deletion strains revealed that two of the gene deletions were dispensable under the conditions tested. The engineered strain was next investigated for the production of vanillin from vanillate and succeeded in preventing formation of the byproduct vanillyl alcohol. A pathway for the biosynthesis of vanillin directly from glucose was introduced and resulted in a 55-fold improvement in vanillin titer when using the RARE strain versus the wild-type strain. Finally, synthesis of the chiral pharmaceutical intermediate L-phenylacetylcarbinol (L-PAC) was demonstrated from benzaldehyde and glucose upon expression of a recombinant mutant pyruvate decarboxylase in the RARE strain. Beyond allowing accumulation of aromatic aldehydes as end products in E. coli, the RARE strain expands the classes of chemicals that can be produced microbially via aldehyde intermediates.

Analysis of femtosecond pump-probe photoelectron-photoion coincidence measurements applying Bayesian probability theory

NASA Astrophysics Data System (ADS)

Rumetshofer, M.; Heim, P.; Thaler, B.; Ernst, W. E.; Koch, M.; von der Linden, W.

2018-06-01

Ultrafast dynamical processes in photoexcited molecules can be observed with pump-probe measurements, in which information about the dynamics is obtained from the transient signal associated with the excited state. Background signals provoked by pump and/or probe pulses alone often obscure these excited-state signals. Simple subtraction of pump-only and/or probe-only measurements from the pump-probe measurement, as commonly applied, results in a degradation of the signal-to-noise ratio and, in the case of coincidence detection, the danger of overrated background subtraction. Coincidence measurements additionally suffer from false coincidences, requiring long data-acquisition times to keep erroneous signals at an acceptable level. Here we present a probabilistic approach based on Bayesian probability theory that overcomes these problems. For a pump-probe experiment with photoelectron-photoion coincidence detection, we reconstruct the interesting excited-state spectrum from pump-probe and pump-only measurements. This approach allows us to treat background and false coincidences consistently and on the same footing. We demonstrate that the Bayesian formalism has the following advantages over simple signal subtraction: (i) the signal-to-noise ratio is significantly increased, (ii) the pump-only contribution is not overestimated, (iii) false coincidences are excluded, (iv) prior knowledge, such as positivity, is consistently incorporated, (v) confidence intervals are provided for the reconstructed spectrum, and (vi) it is applicable to any experimental situation and noise statistics. Most importantly, by accounting for false coincidences, the Bayesian approach allows us to run experiments at higher ionization rates, resulting in a significant reduction of data acquisition times. The probabilistic approach is thoroughly scrutinized by challenging mock data. The application to pump-probe coincidence measurements on acetone molecules enables quantitative interpretations about the molecular decay dynamics and fragmentation behavior. All results underline the superiority of a consistent probabilistic approach over ad hoc estimations.

State-resolved three-dimensional electron-momentum correlation in nonsequential double ionization of benzene

NASA Astrophysics Data System (ADS)

Winney, Alexander H.; Lin, Yun Fei; Lee, Suk Kyoung; Adhikari, Pradip; Li, Wen

2016-03-01

We report state-resolved electron-momentum correlation measurement of strong-field nonsequential double ionization in benzene. With a novel coincidence detection apparatus, highly efficient triple coincidence (electron-electron dication) and quadruple coincidence (electron-electron-cation-cation) are used to resolve the final ionic states and to characterize three-dimensional (3D) electron-momentum correlation. The primary states associated with dissociative and nondissociative dications are assigned. A 3D momentum anticorrelation is observed for the electrons in coincidence with dissociative benzene dication states whereas such a correlation is absent for nondissociative dication states.

Molecular Rotors for Universal Quantitation of Nanoscale Hydrophobic Interfaces in Microplate Format.

PubMed

Bisso, Paul W; Tai, Michelle; Katepalli, Hari; Bertrand, Nicolas; Blankschtein, Daniel; Langer, Robert

2018-01-10

Hydrophobic self-assembly pairs diverse chemical precursors and simple formulation processes to access a vast array of functional colloids. Exploration of this design space, however, is stymied by lack of broadly general, high-throughput colloid characterization tools. Here, we show that a narrow structural subset of fluorescent, zwitterionic molecular rotors, dialkylaminostilbazolium sulfonates [DASS] with intermediate-length alkyl tails, fills this major analytical void by quantitatively sensing hydrophobic interfaces in microplate format. DASS dyes supersede existing interfacial probes by avoiding off-target fluorogenic interactions and dye aggregation while preserving hydrophobic partitioning strength. To illustrate the generality of this approach, we demonstrate (i) a microplate-based technique for measuring mass concentration of small (20-200 nm), dilute (submicrogram sensitivity) drug delivery nanoparticles; (ii) elimination of particle size, surfactant chemistry, and throughput constraints on quantifying the complex surfactant/metal oxide adsorption isotherms critical for environmental remediation and enhanced oil recovery; and (iii) more reliable self-assembly onset quantitation for chemically and structurally distinct amphiphiles. These methods could streamline the development of nanotechnologies for a broad range of applications.

Physical activity and lung cancer among non-smokers: A pilot molecular epidemiologic study within EPIC

PubMed Central

RUNDLE, ANDREW; RICHIE, JOHN; STEINDORF, KAREN; PELUSO, MARCO; OVERVAD, KIM; RAASCHOU-NIELSEN, OLE; CLAVEL-CHAPELON, FRANCOISE; LINSEISEN, JACOB P.; BOEING, HEINER; TRICHOPOULOU, ANTONIA; PALLI, DOMENICO; KROGH, VITTORIO; TUMINO, ROSARIO; PANICO, SALVATORE; BUENO-DE-MESQUITA, HENDRIK B.; PEETERS, PETRA H.; LUND, EILIV; GONZALEZ, CARLOS A.; MARTINEZ, CARMEN; DORRONSORO, MIREN; BARRICARTE, AURELIO; TORMO, M. JOSE; QUIROS, JOSÈ R.; AGUDO, ANTONIO; BERGLUND, GORAN; JARVHOLM, BENGT; BINGHAM, SHEILA; KEY, TIMOTHY J.; GORMALLY, EMMANUELLE; SARACCI, RODOLFO; KAAKS, RUDOLF; RIBOLI, ELIO; VINEIS, PAOLO

2013-01-01

The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by 32P-postlabeling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared to the first quartile, the fourth quartile of recreational physical activity was associated with lower lung cancer risk [odds ratio=0.56 (0.35–0.90)], higher GSH levels [+1.87 micro mole GSH/gram haemoglobin, p=0.04] but not with the presence of high levels of adducts [odds ratio=1.05 (0.38–2.86)]. Despite being associated with recreational physical activity, in these small scale pilot analyses GSH levels were not associated with lung cancer risk, [odds ratio=0.95 (0.84 – 1.07) per unit increase in glutathione levels]. Household and occupational activity was not associated with lung cancer risk or biomarker levels. PMID:20050820

Personalising e-learning modules: targeting Rasmussen levels using XML.

PubMed

Renard, J M; Leroy, S; Camus, H; Picavet, M; Beuscart, R

2003-01-01

The development of Internet technologies has made it possible to increase the number and the diversity of on-line resources for teachers and students. Initiatives like the French-speaking Virtual Medical University Project (UMVF) try to organise the access to these resources. But both teachers and students are working on a partly redundant subset of knowledge. From the analysis of some French courses we propose a model for knowledge organisation derived from Rasmussen's stepladder. In the context of decision-making Rasmussen has identified skill-based, rule-based and knowledge-based levels for the mental process. In the medical context of problem-solving, we apply these three levels to the definition of three students levels: beginners, intermediate-level learners, experts. Based on our model, we build a representation of the hierarchical structure of data using XML language. We use XSLT Transformation Language in order to filter relevant data according to student level and to propose an appropriate display on students' terminal. The model and the XML implementation we define help to design tools for building personalised e-learning modules.

Seasonal plasticity of auditory hair cell frequency sensitivity correlates with plasma steroid levels in vocal fish

PubMed Central

Rohmann, Kevin N.; Bass, Andrew H.

2011-01-01

SUMMARY Vertebrates displaying seasonal shifts in reproductive behavior provide the opportunity to investigate bidirectional plasticity in sensory function. The midshipman teleost fish exhibits steroid-dependent plasticity in frequency encoding by eighth nerve auditory afferents. In this study, evoked potentials were recorded in vivo from the saccule, the main auditory division of the inner ear of most teleosts, to test the hypothesis that males and females exhibit seasonal changes in hair cell physiology in relation to seasonal changes in plasma levels of steroids. Thresholds across the predominant frequency range of natural vocalizations were significantly less in both sexes in reproductive compared with non-reproductive conditions, with differences greatest at frequencies corresponding to call upper harmonics. A subset of non-reproductive males exhibiting an intermediate saccular phenotype had elevated testosterone levels, supporting the hypothesis that rising steroid levels induce non-reproductive to reproductive transitions in saccular physiology. We propose that elevated levels of steroids act via long-term (days to weeks) signaling pathways to upregulate ion channel expression generating higher resonant frequencies characteristic of non-mammalian auditory hair cells, thereby lowering acoustic thresholds. PMID:21562181

The impact of natural products upon modern drug discovery.

PubMed

Ganesan, A

2008-06-01

In the period 1970-2006, a total of 24 unique natural products were discovered that led to an approved drug. We analyze these successful leads in terms of drug-like properties, and show that they can be divided into two equal subsets. The first falls in the 'Lipinski universe' and complies with the Rule of Five. The second is a 'parallel universe' that violates the rules. Nevertheless, the latter compounds remain largely compliant in terms of logP and H-bond donors, highlighting the importance of these two metrics in predicting bioavailability. Natural products are often cited as an exception to Lipinski's rules. We believe this is because nature has learned to maintain low hydrophobicity and intermolecular H-bond donating potential when it needs to make biologically active compounds with high molecular weight and large numbers of rotatable bonds. In addition, natural products are more likely than purely synthetic compounds to resemble biosynthetic intermediates or endogenous metabolites, and hence take advantage of active transport mechanisms. Interestingly, the natural product leads in the Lipinski and parallel universe had an identical success rate (50%) in delivering an oral drug.

Risk assessment of nonylphenol and its ethoxylates in U.S. river water and sediment

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

Weeks, J.A.; Adams, W.J.; Guiney, P.D.

1994-12-31

A comprehensive program addressing the risks of nonylphenol (NP) and its ethoxylates (NPE) in aquatic environments of the United States has been undertaken by the Alkyl Phenol Ethoxylates Panel of the Chemical Manufacturers Association cooperating with EPA. Several hundred million pounds of NPE surfactants are used in the US each year. Nonylphenol can be an intermediate product of degradation of nonylphenol ethoxylates. A survey of those river reaches most likely to contain NPE and NP residues was conducted based on a random sample of a subset of the EPA River Reach File defined by certain selection criteria. Applying enhanced analyticalmore » techniques, little or no NP and NPE were found in river water at most locations, while low levels were usually detected in sediment. Acute and chronic toxicity tests using a variety of organisms have also been completed. New results are presented for shrimp, fish, tadpoles, midges, and algae. The risk of NP to the aquatic environment is examined by comparison of observed levels with toxicity benchmarks, and by application of equilibrium partitioning theory to calculate sediment interstitial chemical concentrations.« less

Confirming LBV Candidates Through Variability: A Photometric and Spectroscopic Monitoring Study

NASA Astrophysics Data System (ADS)

Stringfellow, Guy; Gvaramadze, Vasilii

2012-02-01

Luminous Blue Variable (LBV) stars represent an extremely rare class of very luminous, massive stars. About a dozen confirmed Galactic LBV stars are known, which precludes determining a solid evolutionary connection between LBV and other intermediate (e.g. Ofpe/WN9, WNL) phases in the life of very massive stars. Several catalogues of nebulae - rings and shells typical of LBVs - derived from the GLIMPSE and MIPSGAL surveys have recently been published. We conducted a near-IR spectral survey of a large subset of central stars residing within these nebulae and have identified nearly two dozen new candidate LBVs (cLBVs) based on spectral similarity alone; they remain cLBVs until 1-3 mag variability is demonstrated, securing their LBV nature. This marks a significant advancement in the study of massive stars, far outweighing the return from many studies searching for LBVs and WRs the past several decades. Using SMARTS 16 new cLBVs, 3 confirmed LBVs, and 2 previously known cLBVs will undergo photometric IR-monitoring, with 6 new cLBVs monitored spectroscopically (already being photometrically monitored elsewhere).

Confirming LBV Candidates Through Variability: A Photometric and Spectroscopic Monitoring Study

NASA Astrophysics Data System (ADS)

Stringfellow, Guy; Gvaramadze, Vasilii

2011-08-01

Luminous Blue Variable (LBV) stars represent an extremely rare class of very luminous, massive stars. About a dozen confirmed Galactic LBV stars are known, which precludes determining a solid evolutionary connection between LBV and other intermediate (e.g. Ofpe/WN9, WNL) phases in the life of very massive stars. Several catalogues of nebulae - rings and shells typical of LBVs - derived from the GLIMPSE and MIPSGAL surveys have recently been published. We conducted a near-IR spectral survey of a large subset of central stars residing within these nebulae and have identified nearly two dozen new candidate LBVs (cLBVs) based on spectral similarity alone; they remain cLBVs until 1-3 mag variability is demonstrated, securing their LBV nature. This marks a significant advancement in the study of massive stars, far outweighing the return from many studies searching for LBVs and WRs the past several decades. Using SMARTS 16 new cLBVs, 3 confirmed LBVs, and 2 previously known cLBVs will undergo photometric IR-monitoring, with 6 new cLBVs monitored spectroscopically (already being photometrically monitored elsewhere).

Ebf2 is required for development of dopamine neurons in the midbrain periaqueductal gray matter of mouse.

PubMed

Yang, Qiaoqiao; Liu, Shuxi; Yin, Min; Yin, Yanqing; Zhou, Guomin; Zhou, Jiawei

2015-11-01

Dopaminergic (DA) neurons in the midbrain ventral periaqueductal gray matter (PAG) play critical roles in various physiological and pathophysiological processes including sleep-wake rhyme, antinociception, and drug addiction. However, the molecular mechanisms underlying their development are poorly understood. Here, we showed that PAG DA neurons arose as early as E15.5 in mouse embryos. During the prenatal period, the majority of PAG DA neurons was distributed in the intermediate and caudal regions of the PAG. In the postnatal brain, ∼50% of PAG DA neurons were preferentially located in the caudal portion of the PAG. Moreover, transcription factor early B-cell factor 2 (Ebf2) was transiently expressed in a subset of DA neurons in embryonic ventral mesencephalon. Functional analysis revealed that loss of Ebf2 in vivo caused a marked reduction in the number of DA neurons in the midbrain PAG but not in the substantia nigra and ventral tegmental area. Thus, Ebf2 is identified as a novel and important regulator selectively required for midbrain PAG DA neuron development. © 2015 Wiley Periodicals, Inc.

Usability-driven pruning of large ontologies: the case of SNOMED CT.

PubMed

López-García, Pablo; Boeker, Martin; Illarramendi, Arantza; Schulz, Stefan

2012-06-01

To study ontology modularization techniques when applied to SNOMED CT in a scenario in which no previous corpus of information exists and to examine if frequency-based filtering using MEDLINE can reduce subset size without discarding relevant concepts. Subsets were first extracted using four graph-traversal heuristics and one logic-based technique, and were subsequently filtered with frequency information from MEDLINE. Twenty manually coded discharge summaries from cardiology patients were used as signatures and test sets. The coverage, size, and precision of extracted subsets were measured. Graph-traversal heuristics provided high coverage (71-96% of terms in the test sets of discharge summaries) at the expense of subset size (17-51% of the size of SNOMED CT). Pre-computed subsets and logic-based techniques extracted small subsets (1%), but coverage was limited (24-55%). Filtering reduced the size of large subsets to 10% while still providing 80% coverage. Extracting subsets to annotate discharge summaries is challenging when no previous corpus exists. Ontology modularization provides valuable techniques, but the resulting modules grow as signatures spread across subhierarchies, yielding a very low precision. Graph-traversal strategies and frequency data from an authoritative source can prune large biomedical ontologies and produce useful subsets that still exhibit acceptable coverage. However, a clinical corpus closer to the specific use case is preferred when available.

Ovarian phagocyte subsets and their distinct tissue distribution patterns.

PubMed

Carlock, Colin; Wu, Jean; Zhou, Cindy; Ross, April; Adams, Henry; Lou, Yahuan

2013-01-01

Ovarian macrophages, which play critical roles in various ovarian events, are probably derived from multiple lineages. Thus, a systemic classification of their subsets is a necessary first step for determination of their functions. Utilizing antibodies to five phagocyte markers, i.e. IA/IE (major histocompatibility complex class II), F4/80, CD11b (Mac-1), CD11c, and CD68, this study investigated subsets of ovarian phagocytes in mice. Three-color immunofluorescence and flow cytometry, together with morphological observation on isolated ovarian cells, demonstrated complicated phenotypes of ovarian phagocytes. Four macrophage and one dendritic cell subset, in addition to many minor phagocyte subsets, were identified. A dendritic cell-like population with a unique phenotype of CD11c(high)IA/IE⁻F4/80⁻ was also frequently observed. A preliminary age-dependent study showed dramatic increases in IA/IE⁺ macrophages and IA/IE⁺ dendritic cells after puberty. Furthermore, immunofluorescences on ovarian sections showed that each subset displayed a distinct tissue distribution pattern. The pattern for each subset may hint to their role in an ovarian function. In addition, partial isolation of ovarian macrophage subset using CD11b antibodies was attempted. Establishment of this isolation method may have provided us a tool for more precise investigation of each subset's functions at the cellular and molecular levels.

Comparison of satellite reflectance algorithms for estimating chlorophyll-a in a temperate reservoir using coincident hyperspectral aircraft imagery and dense coincident surface observations

EPA Science Inventory

We analyzed 10 established and 4 new satellite reflectance algorithms for estimating chlorophyll-a (Chl-a) in a temperate reservoir in southwest Ohio using coincident hyperspectral aircraft imagery and dense water truth collected within one hour of image acquisition to develop si...

Using OPeNDAP's Data-Services Framework to Lift Mash-Ups above Blind Dates

NASA Astrophysics Data System (ADS)

Gallagher, J. H. R.; Fulker, D. W.

2015-12-01

OPeNDAP's data-as-service framework (Hyrax) matches diverse sources with many end-user tools and contexts. Keys to its flexibility include: A data model embracing tabular data alongside n-dim arrays and other structures useful in geoinformatics. A REST-like protocol that supports—via suffix notation—a growing set of output forms (netCDF, XML, etc.) plus a query syntax for subsetting. Subsetting applies (via constraints on column values) to tabular data or (via constraints on indices or coordinates) to array-style data . A handler-style architecture that admits a growing set of input types. Community members may contribute handlers, making Hyrax effective as middleware, where N sources are mapped to M outputs with order N+M effort (not NxM). Hyrax offers virtual aggregations of source data, enabling granularity aimed at users, not data-collectors. OPeNDAP-access libraries exist in multiple languages, including Python, Java, and C++. Recent enhancements are increasing this framework's interoperability (i.e., its mash-up) potential. Extensions implemented as servlets—running adjacent to Hyrax—are enriching the forms of aggregation and enabling new protocols: User-specified aggregations, namely, applying a query to (huge) lists of source granules, and receiving one (large) table or zipped netCDF file. OGC (Open Geospatial Consortium) protocols, WMS and WCS. A Webification (W10n) protocol that returns JavaScript Object Notation (JSON). Extensions to OPeNDAP's query language are reducing transfer volumes and enabling new forms of inspection. Advances underway include: Functions that, for triangular-mesh sources, return sub-meshes spec'd via geospatial bounding boxes. Functions that, for data from multiple, satellite-borne sensors (with differing orbits), select observations based on coincidence. Calculations of means, histograms, etc. that greatly reduce output volumes.. Paths for communities to contribute new server functions (in Python, e.g.) that data providers may incorporate into Hyrax via installation parameters. One could say Hyrax itself is a mash-up, but we suggest it as an instrument for a mash-up artist's toolbox. This instrument can support mash-ups built on netCDF files, OGC protocols, JavaScript Web pages, and/or programs written in Python, Java, C or C++.

Anomalies of the CD8+ T cell pool in haemochromatosis: HLA-A3-linked expansions of CD8+CD28- T cells.

PubMed

Arosa, F A; Oliveira, L; Porto, G; da Silva, B M; Kruijer, W; Veltman, J; de Sousa, M

1997-03-01

The present study consists of a phenotypic and functional characterization of peripheral blood T lymphocytes in a group of 21 patients with hereditary haemochromatosis (HH), an MHC class I-linked genetic disease resulting in iron overload, and a group of 30 healthy individuals, both HLA-phenotyped. The HH patients studied showed an increased percentage of CD8+ CD28- T cells with a corresponding reduction in the percentage of CD8+ CD28+ T cells in peripheral blood relative to healthy blood donors. No anomalies of CD28 expression were found in the CD4+ subset. The presence of the HLA-A3 antigen but not age accounted for these imbalances. Thus, an apparent failure of the CD8+ CD28+ T cell population 'to expand', coinciding with an 'expansion' of CD8+ CD28- T cells in peripheral blood of HLA-A3+ but not HLA-A3- HH patients was observed when compared with the respective HLA-A3-matched control group. A significantly higher percentage of HLA-DR+ but not CD45RO+ cells was also found within the peripheral CD8+ T cell subset in HH patients relative to controls. Phytohaemagglutinin (PHA) stimulation of peripheral blood mononuclear cells (PBMC) for 5 days showed: (i) that CD8+ CD28+ T cells both in controls and HH were able to expand in vitro; (ii) that CD8+ CD28- T cells decreased markedly after activation in controls but not in HH patients. Moreover, functional studies showed that CD8+ cytotoxic T lymphocytes (CTL) from HH patients exhibited a diminished cytotoxic activity (approx. two-fold) in standard 51Cr-release assays when compared with CD8+ CTL from healthy controls. The present results provide additional evidence for the existence of phenotypic and functional anomalies of the peripheral CD8+ T cell pool that may underlie the clinical heterogeneity of this iron overload disease. They are of particular relevance given the recent discovery of a novel mutated MHC class I-like gene in HH.

Anomalies of the CD8+ T cell pool in haemochromatosis: HLA-A3-linked expansions of CD8+CD28− T cells

PubMed Central

AROSA, F A; OLIVEIRA, L; PORTO, G; DA SILVA, B M; KRUIJER, W; VELTMAN, J; DE SOUSA, M

1997-01-01

The present study consists of a phenotypic and functional characterization of peripheral blood T lymphocytes in a group of 21 patients with hereditary haemochromatosis (HH), an MHC class I-linked genetic disease resulting in iron overload, and a group of 30 healthy individuals, both HLA-phenotyped. The HH patients studied showed an increased percentage of CD8+ CD28− T cells with a corresponding reduction in the percentage of CD8+ CD28+ T cells in peripheral blood relative to healthy blood donors. No anomalies of CD28 expression were found in the CD4+ subset. The presence of the HLA-A3 antigen but not age accounted for these imbalances. Thus, an apparent failure of the CD8+ CD28+ T cell population ‘to expand’, coinciding with an ‘expansion’ of CD8+ CD28− T cells in peripheral blood of HLA-A3+ but not HLA-A3− HH patients was observed when compared with the respective HLA-A3-matched control group. A significantly higher percentage of HLA-DR+ but not CD45RO+ cells was also found within the peripheral CD8+ T cell subset in HH patients relative to controls. Phytohaemagglutinin (PHA) stimulation of peripheral blood mononuclear cells (PBMC) for 5 days showed: (i) that CD8+ CD28+ T cells both in controls and HH were able to expand in vitro; (ii) that CD8+ CD28− T cells decreased markedly after activation in controls but not in HH patients. Moreover, functional studies showed that CD8+ cytotoxic T lymphocytes (CTL) from HH patients exhibited a diminished cytotoxic activity (approx. two-fold) in standard 51Cr-release assays when compared with CD8+ CTL from healthy controls. The present results provide additional evidence for the existence of phenotypic and functional anomalies of the peripheral CD8+ T cell pool that may underlie the clinical heterogeneity of this iron overload disease. They are of particular relevance given the recent discovery of a novel mutated MHC class I-like gene in HH. PMID:9067531

Glycinergic inhibition tunes coincidence detection in the auditory brainstem

PubMed Central

Myoga, Michael H.; Lehnert, Simon; Leibold, Christian; Felmy, Felix; Grothe, Benedikt

2014-01-01

Neurons in the medial superior olive (MSO) detect microsecond differences in the arrival time of sounds between the ears (interaural time differences or ITDs), a crucial binaural cue for sound localization. Synaptic inhibition has been implicated in tuning ITD sensitivity, but the cellular mechanisms underlying its influence on coincidence detection are debated. Here we determine the impact of inhibition on coincidence detection in adult Mongolian gerbil MSO brain slices by testing precise temporal integration of measured synaptic responses using conductance-clamp. We find that inhibition dynamically shifts the peak timing of excitation, depending on its relative arrival time, which in turn modulates the timing of best coincidence detection. Inhibitory control of coincidence detection timing is consistent with the diversity of ITD functions observed in vivo and is robust under physiologically relevant conditions. Our results provide strong evidence that temporal interactions between excitation and inhibition on microsecond timescales are critical for binaural processing. PMID:24804642

Evidence for Coincident Fusion Products Using Silicon Surface-barrier Detectors

NASA Astrophysics Data System (ADS)

Jones, Steven; Scott, Mark; Keeney, Frank

2002-10-01

We report experimental results showing coincident proton and triton production from the reaction: d + d --> t (1.01 MeV) + p (3.02 MeV). Partially-deuterided thin titanium foils were positioned between two silicon surface-barrier detectors which were mounted in a small cylindrical vacuum chamber which also served as a Faraday cage. We performed Monte Carlo studies using the SRIM code to determine the expected energies of arriving particles after they exit the host foil. The dual-coincidence requirement reduces background to very low levels so that low yields from very thin TiD foils can be readily detected. In one sequence of experiments, we observed 74 foreground coincidences in the regions of interest compared with 24 background counts; the statistical significance is approximately ten standard deviations. A striking advance is that the repeatability from the dual-coincidence experiments is currently greater than 70%.

Permutational symmetries for coincidence rates in multimode multiphotonic interferometry

NASA Astrophysics Data System (ADS)

Khalid, Abdullah; Spivak, Dylan; Sanders, Barry C.; de Guise, Hubert

2018-06-01

We obtain coincidence rates for passive optical interferometry by exploiting the permutational symmetries of partially distinguishable input photons, and our approach elucidates qualitative features of multiphoton coincidence landscapes. We treat the interferometer input as a product state of any number of photons in each input mode with photons distinguished by their arrival time. Detectors at the output of the interferometer count photons from each output mode over a long integration time. We generalize and prove the claim of Tillmann et al. [Phys. Rev. X 5, 041015 (2015), 10.1103/PhysRevX.5.041015] that coincidence rates can be elegantly expressed in terms of immanants. Immanants are functions of matrices that exhibit permutational symmetries and the immanants appearing in our coincidence-rate expressions share permutational symmetries with the input state. Our results are obtained by employing representation theory of the symmetric group to analyze systems of an arbitrary number of photons in arbitrarily sized interferometers.

Transmissivity and water quality of water-producing zones in the intermediate aquifer system, Sarasota County, Florida

USGS Publications Warehouse

Knochenmus, L.A.; Bowman, Geronia

1998-01-01

The intermediate aquifer system is an important water source in Sarasota County, Florida, because the quality of water in it is usually better than that in the underlying Upper Floridan aquifer. The intermediate aquifer system consists of a group of up to three water-producing zones separated by less-permeable units that restrict the vertical movement of ground water between zones. The diverse lithology, that makes up the intermediate aquifer system, reflects the variety of depositional environments that occurred during the late Oligocene and Miocene epochs. Slight changes in the depositional environment resulted in aquifer heterogeneity, creating both localized connection between water-producing zones and abrupt culmination of water-producing zones that are not well documented. Aquifer heterogeneity results in vertical and areal variability in hydraulic and water-quality properties. The uppermost water-producing zone is designated producing zone 1 but is not extensively used because of its limited production capability and limited areal extent. The second water-producing zone is designated producing zone 2, and most of the domestic- and irrigation-supply wells in the area are open to this zone. Additionally, producing zone 2 is utilized for public supply in southern coastal areas of Sarasota County. Producing zone 3 is the lowermost and most productive water-producing zone in the intermediate aquifer system. Public-supply well fields serving the cities of Sarasota and Venice, as well as the Plantation and Mabry Carlton Reserve well fields, utilize producing zone 3. Heads within the intermediate aquifer system generally increase with aquifer depth. However, localized head-gradient reversals occur in the study area, coinciding with sites of intense ground-water withdrawals. Heads in producing zones 1, 2, and 3 range from 1 to 23, 0.2 to 34, and 7 to 42 feet above sea level, respectively. Generally, an upward head gradient exists between producing zones 3 and 2. However, an upward head gradient between producing zones 2 and 1 does not consistently occur throughout Sarasota County, probably the result of greater ground-water withdrawals from producing zone 2 than from producing zone 1. The transmissivity of the intermediate aquifer system is spatially variable. Specific-capacity data from selected wells penetrating producing zones 2 and 3, were used to estimate transmissivity. Estimated transmissivity values for producing zones 2 and 3 range from about 100 to 26,000 feet squared per day and from about 1,300 to 6,200 feet squared per day, respectively. Because the capacity of specific water-producing zones is highly variable from site to site, estimating the performance of a specific water-producing zone as a water resource is difficult. Water samples collected during the study were analyzed for major-ion concentrations. Generally, bicarbonate type water from rock interaction occurs in northern Sarasota County; enriched calcium-magnesium-sulfate type water from deeper aquifers occurs in central Sarasota County; and sodium-chloride type water from saltwater mixing occurs in southern Sarasota County. In some areas of northern Sarasota County, the major-ion concentrations in water are lower in producing zone 2 than in producing zone 1. Major-ion concentrations in water are higher in producing zone 3 throughout the study area. A major objective of the study was to evaluate hydraulic and water-quality data to determine distinctions that could be used to characterize a particular producing zone. However, data indicate that both hydraulic and water-quality properties are highly variable within and between zones, and are more related to the degree of connection between and areal extent of water-producing zones than to aquifer depth and distance from the coast.

A Change in Igneous Activity of the Jack Hills Zircon Sources ca. 3.9 Ga

NASA Astrophysics Data System (ADS)

Bell, E. A.; Harrison, T. M.

2010-12-01

New Ti-in-zircon crystallization temperature (Txlln) data for <4 Ga Jack Hills zircons reveal that the tight clustering of Hadean grains around a Txlln of 680°C, possibly indicative of felsic-to-intermediate minimum melting conditions, continues to ~3.92 Ga. Between 3.92-3.82 Ga the 680°C clustering ceases and most concordant grains cluster around an apparent Txlln of 610°C. A small group of zircons with higher Txlln (~750°C), present during the Hadean, is also observed during this period. After 3.82 Ga a Hadean-like distribution resumes for ~100 Ma. This large, concordant, low-Ti group at ~3.9 Ga is statistically distinct from the Hadean distribution and appears to be unique in the Jack Hills zircon record. The existence of coeval high- and low-Ti groups suggests that two distinct zircon-forming processes are distinguishable ~3.9 Ga, unlike during the Hadean. The significant numbers of zircons with apparent Txlln below 600°C may be suggestive of subsolidus formation, since igneous units with solidii below 600°C are relatively rare. The higher-Ti group is more consistent with an intermediate to mafic igneous origin but metamorphic overprinting or subsolidus formation at granulite grade cannot be ruled out by Txlln alone. A substantial proportion of the high-Ti group display oscillatory and disrupted oscillatory zoning in cathodoluminescence images, usually indicative of igneous origins and later metamorphism, respectively; most low-Ti grains are homogeneous. Several of each group display patchy zonation indicative of metamorphic overprinting. Although several grains with apparent Txlln >600°C display oscillatory zonation, the majority of the low-Ti group do not show textural evidence for igneous origins. We interpret these results to indicate the transition from a mechanism(s) that produced dominantly 680°C apparent zircon temperatures at ca. 3.9 Ga to include a new zircon-forming process in the sediment source(s), likely a protracted period of metamorphism (possibly with minor crustal anatexis). ~750°C magmatism (probably intermediate to mafic) also occurs during this time period. This change in geologic conditions coincides in time with the Late Heavy Bombardment, and an exogenic origin for the event is not necessary but cannot be ruled out at the present time.