Inheritance of downy mildew (Plasmopara viticola) and anthracnose (Sphaceloma ampelinum) resistance in grapevines.

PubMed

Poolsawat, O; Mahanil, S; Laosuwan, P; Wongkaew, S; Tharapreuksapong, A; Reisch, B I; Tantasawat, P A

2013-12-13

Downy mildew (Plasmopara viticola) and anthracnose (Sphaceloma ampelinum) are two of the major diseases of most grapevine (Vitis vinifera L.) cultivars grown in Thailand. Therefore, breeding grapevines for improved downy mildew and anthracnose resistance is crucial. Factorial crosses were made between three downy mildew and/or anthracnose resistant lines ('NY88.0517.01', 'NY65.0550.04', and 'NY65.0551.05'; male parents) and two or three susceptible cultivars of V. vinifera ('Black Queen', 'Carolina Black Rose', and/or 'Italia'; female parents). F1 hybrid seedlings were evaluated for downy mildew and anthracnose resistance using a detached/excised leaf assay. For both diseases, the general combining ability (GCA) variance among male parents was significant, while the variance of GCA among females and the specific combining ability (SCA) variance were not significant, indicating the prevalence of additive over non-additive gene actions. The estimated narrow sense heritabilities of downy mildew and anthracnose resistance were 55.6 and 79.2%, respectively, suggesting that downy mildew/anthracnose resistance gene(s) were highly heritable. The 'Carolina Black Rose x NY65.0550.04' cross combination is recommended for future use.

Combining ability for yield and fruit quality in the pepper Capsicum annuum.

PubMed

do Nascimento, N F F; do Rêgo, E R; Nascimento, M F; Bruckner, C H; Finger, F L; do Rêgo, M M

2014-04-29

The objective of this study was to determine the effects of the general and specific combining abilities (GCA and SCA, respectively) of 15 characteristics and to evaluate the most promising crosses and the reciprocal effect between the hybrids of six parents of the Capsicum annuum species. Six parents, belonging to the Horticultural Germplasm Bank of Centro de Ciências Agrárias of Universidade Federal da Paraíba, were crossed in complete diallel manner. The 30 hybrids generated and the parents were then analyzed in a completely randomized design with three replicates. The data were submitted to analysis of variance at 1% probability, and the means were grouped by the Scott-Knott test at 1% probability. The diallel analysis was performed according to the Griffing method, model I and fixed model. Both additive and non-additive effects influenced the hybrids' performance, as indicated by the GCA/SCA ratio. The non-additive effects, epistasis and/or dominance, played a more important role than the additive effects in pedicel length, pericarp thickness, fresh matter, dry matter content, seed yield per fruit, fruit yield per plant, days to fructification, and total soluble solids. The GCA effects were more important than the SCA effects in the fruit weight, fruit length and diameter, placenta length, yield, vitamin C, and titratable acidity characteristics. The results found here clearly show that ornamental pepper varieties can be developed through hybridization in breeding programs with C. annuum.

A Longitudinal Twin Study of General Cognitive Ability over Four Decades

ERIC Educational Resources Information Center

Lyons, Michael J.; Panizzon, Matthew S.; Liu, Weijian; McKenzie, Ruth; Bluestone, Noah J.; Grant, Michael D.; Franz, Carol E.; Vuoksimaa, Eero P.; Toomey, Rosemary; Jacobson, Kristen C.; Reynolds, Chandra A.; Kremen, William S.; Xian, Hong

2017-01-01

In this longitudinal study we examined the stability of general cognitive ability (GCA), as well as heterogeneity and genetic and environmental influences underlying individual differences in change. We investigated GCA from young adulthood through late midlife in 1,288 Vietnam Era Twin Study of Aging participants at ages ~20, ~56, and ~62 years.…

Combining-ability for cacao (Theobroma cacao L.) yield components under southern Bahia conditions.

PubMed

Dias, L A; Kageyama, P Y

1995-03-01

The objective of this study was to assess five cacao cultivars (selfs) and 20 hybrids with regard to their general-and specific-combining ability for yield components using method 1, model I, of the diallel analysis system. The selfings and the hybrids were obtained through controlled crossings, tested in the field in a random block design with four replications and plots containing 16 plants. The experiment was set up in the Centro de Pesquisas do Cacau, in Itabuna, Bahia, Brasil, in 1975. The characteristics studied were: the number of healthy and collected fruits per plant (NHFP and NCFP), the weight of humid seeds per plant and per fruit (WHSP and WHSF), and the percentage of diseased fruits per plant (PDFP), for 5 years (1986-1990). The F-test values, highly significant for general combining ability (GCA) and specific combining ability (SCA), demonstrated the existence of variability for both effects. However, the effects of SCA were greater than those of GCA, when compared in terms of the average squared effects. This condition held for the characteristics NHFP, NCFP and WHSP, which shows the relative importance of the non-additive genetic effects over the additive effects. The reciprocal effects did not show significance. Breeding methods which explore the additive portion of genetic variance should be employed for obtaining higher-yielding cacao and high seed weight. For this, the segregant populations should involve cultivars CEPEC 1, SIAL 169 and ICS 1. Combinations involving the cultivar ICS 1 presented the most favorable results for the characteristics WHSP and WHSF, where the hybrid SIAL 169 x ICS 1 and its reciprocal were outstanding.

Diallel analysis of provitamin A carotenoid and dry matter content in cassava (Manihot esculenta Crantz)

PubMed Central

Esuma, Williams; Kawuki, Robert S.; Herselman, Liezel; Labuschagne, Maryke Tine

2016-01-01

Global efforts are underway to biofortify cassava (Manihot esculenta Crantz) with provitamin A carotenoids to help combat dietary vitamin A deficiency afflicting the health of more than 500 million resource-poor people in Sub-Saharan Africa. To further the biofortification initiative in Uganda, a 6×6 diallel analysis was conducted to estimate combining ability of six provitamin A clones and gene actions controlling total carotenoid content (TCC), dry matter content (DMC) in cassava roots and other relevant traits. Fifteen F1 families generated from the diallel crosses were evaluated in two environments using a randomized complete block design. General combining ability (GCA) effects were significant for TCC and DMC, suggesting the relative importance of additive gene effects in controlling these traits in cassava. On the other hand, non-additive effects were predominant for root and shoot weight. MH02-073HS, with the highest level of TCC, was the best general combiner for TCC while NASE 3, a popular white-fleshed variety grown by farmers in Uganda, was the best general combiner for DMC. Such progenitors with superior GCA effects could form the genetic source for future programs targeting cassava breeding for TCC and DMC. A negative correlation was observed between TCC and DMC, which will require breeding strategies to combine both traits for increased adoption of provitamin A cassava varieties. PMID:27795688

Dopamine D1 receptor density in the mPFC responds to cognitive demands and receptor turnover contributes to general cognitive ability in mice.

PubMed

Wass, Christopher; Sauce, Bruno; Pizzo, Alessandro; Matzel, Louis D

2018-03-14

In both humans and mice, performance on tests of intelligence or general cognitive ability (GCA) is related to dopamine D1 receptor-mediated activity in the prelimbic cortex, and levels of DRD1 mRNA predict the GCA of mice. Here we assessed the turnover rate of D1 receptors as well as the expression level of the D1 chaperone protein (DRiP78) in the medial PPC (mPFC) of mice to determine whether rate of receptor turnover was associated with variations in the GCA of genetically heterogeneous mice. Following assessment of GCA (aggregate performance on four diverse learning tests) mice were administered an irreversible dopamine receptor antagonist (EEDQ), after which the density of new D1 receptors were quantified. GCA was positively correlated with both the rate of D1 receptor recovery and levels of DRiP78. Additionally, the density of D1 receptors was observed to increase within 60 min (or less) in response to intense demands on working memory, suggesting that a pool of immature receptors was available to accommodate high cognitive loads. These results provide evidence that innate general cognitive abilities are related to D1 receptor turnover rates in the prefrontal cortex, and that an intracellular pool of immature D1 receptors are available to accommodate cognitive demands.

Exploring genotypic variations for improved oil content and healthy fatty acids composition in rapeseed (Brassica napus L.).

PubMed

Ishaq, Muhammad; Razi, Raziuddin; Khan, Sabaz Ali

2017-04-01

Development of new genotypes having high oil content and desirable levels of fatty acid compositions is a major objective of rapeseed breeding programmes. In the current study combining ability was determined for oil, protein, glucosinolates and various fatty acids content using 8 × 8 full diallel in rapeseed (Brassica napus). Highly significant genotypic differences were observed for oil, protein, glucosinolates, oleic acid, linolenic acid and erucic acid content. Mean squares due to general combining ability (GCA), specific combining ability (SCA) and reciprocal combining ability (RCA) were highly significant (P ≤ 0.01) for biochemical traits. Parental line AUP-17 for high oil content and low glucosinolates, genotype AUP-2 for high protein and oleic acids, and AUP-18 for low lenolenic and erucic acid were best general combiners. Based on desirable SCA effects, F 1 hybrids AUP-17 × AUP-20; AUP-2 × AUP-8; AUP-7 × AUP-14; AUP-2 × AUP-9; AUP-7 × AUP-14 and AUP-2 × AUP-9 were found superior involving at least one best general combiner. F 1 hybrids AUP-17 × AUP-20 (for oil content); AUP-2 × AUP-8 (for protein content); AUP-7 × AUP-14 (for glucosinolates); AUP-2 × AUP-9 (for oleic acid); AUP-7 × AUP-14 (for linolenic acid) and AUP-2 × AUP-9 (for erucic acid) were found superior involving at least one best general combiner. As reciprocal crosses of AUP-14 with AUP-7 and AUP-8 were superior had low × low and low × high GCA effects for glucosinolates and oleic acid, respectively therefore, these could be exploited in future rapeseed breeding programmes to develop new lines with good quality. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Optimum allocation of test resources and comparison of breeding strategies for hybrid wheat.

PubMed

Longin, C Friedrich H; Mi, Xuefei; Melchinger, Albrecht E; Reif, Jochen C; Würschum, Tobias

2014-10-01

The use of a breeding strategy combining the evaluation of line per se with testcross performance maximizes annual selection gain for hybrid wheat breeding. Recent experimental studies confirmed a high commercial potential for hybrid wheat requiring the design of optimum breeding strategies. Our objectives were to (1) determine the optimum allocation of the type and number of testers, the number of test locations and the number of doubled haploid lines for different breeding strategies, (2) identify the best breeding strategy and (3) elaborate key parameters for an efficient hybrid wheat breeding program. We performed model calculations using the selection gain for grain yield as target variable to optimize the number of lines, testers and test locations in four different breeding strategies. A breeding strategy (BS2) combining the evaluation of line per se performance and general combining ability (GCA) had a far larger annual selection gain across all considered scenarios than a breeding strategy (BS1) focusing only on GCA. In the combined strategy, the production of testcross seed conducted in parallel with the first yield trial for line per se performance (BS2rapid) resulted in a further increase of the annual selection gain. For the current situation in hybrid wheat, this relative superiority of the strategy BS2rapid amounted to 67 % in annual selection gain compared to BS1. Varying a large number of parameters, we identified the high costs for hybrid seed production and the low variance of GCA in hybrid wheat breeding as key parameters limiting selection gain in BS2rapid.

Genetic Performance and General Combining Ability of Oil Palm Deli dura x AVROS pisifera Tested on Inland Soils

PubMed Central

Noh, A.; Rafii, M. Y.; Saleh, G.; Kushairi, A.; Latif, M. A.

2012-01-01

The performance of 11 oil palm AVROS (Algemene Vereniging van Rubberplanters ter Oostkust van Sumatra) pisiferas was evaluated based on their 40 dura x pisifera (DxP) progenies tested on inland soils, predominantly of Serdang Series. Fresh fruit bunch (FFB) yield of each pisiferas ranged from 121.93 to 143.9 kg palm−1 yr−1 with trial mean of 131.62 kg palm−1 yr−1. Analysis of variance (ANOVA) showed low genetic variability among pisifera parents for most of the characters indicating uniformity of the pisifera population. This was anticipated as the AVROS pisiferas were derived from small population and were inbred materials. However, some of the pisiferas have shown good general combining ability (GCA) for certain important economic traits. Three pisiferas (P1 (0.174/247), P3 (0.174/498), P11 (0.182/308)) were identified of having good GCA for FFB yield while pisiferas P1 (0.174/247), P10 (0.182/348), and P11 (0.182/308) were good combiners for oil-to-bunch ratio (O/B). The narrow genetic base of these materials was the main obstacle in breeding and population improvement. However, efforts have been made to introgress this material with the vast oil palm germplasm collections of MPOB for rectifying the problem. PMID:22701095

Gingival cyst of the adult: regenerative therapy of associated root exposure. A case report and literature review.

PubMed

Kelsey, W Patrick; Kalmar, John R; Tatakis, Dimitris N

2009-12-01

The gingival cyst of the adult (GCA) is an uncommon developmental cyst of odontogenic origin most frequently seen near mandibular canines and premolars and is routinely treated with excisional biopsy. This article presents a case of a GCA treated with a combined regenerative approach and reviews the GCA literature with an emphasis on the clinical aspects of this lesion. A 54 year-old man presented for treatment of generalized severe chronic periodontitis. Clinical examination revealed a cystic lesion in the gingiva of the mandibular canine-premolar area. Radiographs revealed a well-defined radiolucency in the coronal one-third of the tooth roots. Surgical enucleation of the lesion revealed root exposure of the second premolar. Because of the anatomy of the lesion-associated defect, regenerative treatment, using a combination of freeze-dried bone allograft and a collagen membrane, was considered the therapeutic approach of choice. The biopsy revealed histologic features consistent with a GCA. Clinical and radiographic examinations 1 year post-surgery indicated uneventful soft tissue healing and bone fill of the initial defect. The review of the literature revealed only one other case of root exposure associated with GCA and no previous report of regenerative therapy. In rare instances, a GCA lesion may result in tooth-root exposure. In such cases, a combined regenerative treatment approach may be used to achieve resolution.

Quantitative genetic analysis of agronomic and morphological traits in sorghum, Sorghum bicolor

PubMed Central

Mohammed, Riyazaddin; Are, Ashok K.; Bhavanasi, Ramaiah; Munghate, Rajendra S.; Kavi Kishor, Polavarapu B.; Sharma, Hari C.

2015-01-01

The productivity in sorghum is low, owing to various biotic and abiotic constraints. Combining insect resistance with desirable agronomic and morphological traits is important to increase sorghum productivity. Therefore, it is important to understand the variability for various agronomic traits, their heritabilities and nature of gene action to develop appropriate strategies for crop improvement. Therefore, a full diallel set of 10 parents and their 90 crosses including reciprocals were evaluated in replicated trials during the 2013–14 rainy and postrainy seasons. The crosses between the parents with early- and late-flowering flowered early, indicating dominance of earliness for anthesis in the test material used. Association between the shoot fly resistance, morphological, and agronomic traits suggested complex interactions between shoot fly resistance and morphological traits. Significance of the mean sum of squares for GCA (general combining ability) and SCA (specific combining ability) of all the studied traits suggested the importance of both additive and non-additive components in inheritance of these traits. The GCA/SCA, and the predictability ratios indicated predominance of additive gene effects for majority of the traits studied. High broad-sense and narrow-sense heritability estimates were observed for most of the morphological and agronomic traits. The significance of reciprocal combining ability effects for days to 50% flowering, plant height and 100 seed weight, suggested maternal effects for inheritance of these traits. Plant height and grain yield across seasons, days to 50% flowering, inflorescence exsertion, and panicle shape in the postrainy season showed greater specific combining ability variance, indicating the predominance of non-additive type of gene action/epistatic interactions in controlling the expression of these traits. Additive gene action in the rainy season, and dominance in the postrainy season for days to 50% flowering and plant height suggested G X E interactions for these traits. PMID:26579183

Two-stage selection in slash pine produces good gains in fusiform rust resistance

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

Sluder, E.R.

The best 6 of 21 progeny-tested first-generation slash pine selections were crossed in a half diallel to study inheritance patterns of their superior fusiform rust resistance (5 trees) and height (1 tree). Their six first-test progenies were duplicated and included in the study. These two groups of progenies, along with two commercial check lots, were planted on an Upper Coastal Plain and a Flatwoods site in Georgia. At age 10 yr, the 15 progenies in the half diallel averaged 23% rust-infected compared with 54% for the check lots. First-test progenies averaged 30% infected. For percentage infection, the six parents differedmore » in general combining ability (GCA) (0.01>P>0.001) on both test sites and in specific combining ability (0.05>P>0.01) on one site. GCA variation for height was significant (0.05>P>0.01) on one site. The parent selected for height had the highest breeding value for height at age 10 yr. These results show that resistance to the fusiform rust disease, a serious problem in management of the species, can be improved in slash pine. These 6 parents and their 15 progenies in the half-diallel cross are a good source of rust resistance genes for use in slash pine improvement programs.« less

Optimization of a GCaMP calcium indicator for neural activity imaging.

PubMed

Akerboom, Jasper; Chen, Tsai-Wen; Wardill, Trevor J; Tian, Lin; Marvin, Jonathan S; Mutlu, Sevinç; Calderón, Nicole Carreras; Esposti, Federico; Borghuis, Bart G; Sun, Xiaonan Richard; Gordus, Andrew; Orger, Michael B; Portugues, Ruben; Engert, Florian; Macklin, John J; Filosa, Alessandro; Aggarwal, Aman; Kerr, Rex A; Takagi, Ryousuke; Kracun, Sebastian; Shigetomi, Eiji; Khakh, Baljit S; Baier, Herwig; Lagnado, Leon; Wang, Samuel S-H; Bargmann, Cornelia I; Kimmel, Bruce E; Jayaraman, Vivek; Svoboda, Karel; Kim, Douglas S; Schreiter, Eric R; Looger, Loren L

2012-10-03

Genetically encoded calcium indicators (GECIs) are powerful tools for systems neuroscience. Recent efforts in protein engineering have significantly increased the performance of GECIs. The state-of-the art single-wavelength GECI, GCaMP3, has been deployed in a number of model organisms and can reliably detect three or more action potentials in short bursts in several systems in vivo. Through protein structure determination, targeted mutagenesis, high-throughput screening, and a battery of in vitro assays, we have increased the dynamic range of GCaMP3 by severalfold, creating a family of "GCaMP5" sensors. We tested GCaMP5s in several systems: cultured neurons and astrocytes, mouse retina, and in vivo in Caenorhabditis chemosensory neurons, Drosophila larval neuromuscular junction and adult antennal lobe, zebrafish retina and tectum, and mouse visual cortex. Signal-to-noise ratio was improved by at least 2- to 3-fold. In the visual cortex, two GCaMP5 variants detected twice as many visual stimulus-responsive cells as GCaMP3. By combining in vivo imaging with electrophysiology we show that GCaMP5 fluorescence provides a more reliable measure of neuronal activity than its predecessor GCaMP3. GCaMP5 allows more sensitive detection of neural activity in vivo and may find widespread applications for cellular imaging in general.

Optimization of a GCaMP calcium indicator for neural activity imaging

PubMed Central

Akerboom, Jasper; Chen, Tsai-Wen; Wardill, Trevor J.; Tian, Lin; Marvin, Jonathan S.; Mutlu, Sevinç; Calderón, Nicole Carreras; Esposti, Federico; Borghuis, Bart G.; Sun, Xiaonan Richard; Gordus, Andrew; Orger, Michael B.; Portugues, Ruben; Engert, Florian; Macklin, John J.; Filosa, Alessandro; Aggarwal, Aman; Kerr, Rex; Takagi, Ryousuke; Kracun, Sebastian; Shigetomi, Eiji; Khakh, Baljit S.; Baier, Herwig; Lagnado, Leon; Wang, Samuel S.-H.; Bargmann, Cornelia I.; Kimmel, Bruce E.; Jayaraman, Vivek; Svoboda, Karel; Kim, Douglas S.; Schreiter, Eric R.; Looger, Loren L.

2012-01-01

Genetically encoded calcium indicators (GECIs) are powerful tools for systems neuroscience. Recent efforts in protein engineering have significantly increased the performance of GECIs. The state-of-the art single-wavelength GECI, GCaMP3, has been deployed in a number of model organisms and can reliably detect three or more action potentials (APs) in short bursts in several systems in vivo. Through protein structure determination, targeted mutagenesis, high-throughput screening, and a battery of in vitro assays, we have increased the dynamic range of GCaMP3 by several-fold, creating a family of “GCaMP5” sensors. We tested GCaMP5s in several systems: cultured neurons and astrocytes, mouse retina, and in vivo in Caenorhabditis chemosensory neurons, Drosophila larval neuromuscular junction and adult antennal lobe, zebrafish retina and tectum, and mouse visual cortex. Signal-to-noise ratio was improved by at least 2–3-fold. In the visual cortex, two GCaMP5 variants detected twice as many visual stimulus-responsive cells as GCaMP3. By combining in vivo imaging with electrophysiology we show that GCaMP5 fluorescence provides a more reliable measure of neuronal activity than its predecessor GCaMP3. GCaMP5 allows more sensitive detection of neural activity in vivo and may find widespread applications for cellular imaging in general. PMID:23035093

Comparison of element-specific capillary chromotography detectors for the identification of heteroatomic species in coal liquids

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

Mitchell, S.C.; Bartle, K.D.; Holden, K.M.L.

1994-12-31

A series of heteroatom-rich coal and coal-derived liquids have been analysed using gas chromatography (GC) in combination with three different element-selective detectors. Selected chromatograms, including a supercritical extract (Mequinenza lignite) and aromatic fractions isolated from coal tar pitch samples are presented. In each case a series of sulphur- and/or nitrogen-containing compounds have been identified using either flame photometric detection (GC/FID/FPD) or nitrogen-phosphorous detection (GC/FID/NPD) and the information compared with that obtained from a GC coupled to an atomic emission detector (GC-AED). Preliminary results have demonstrated the relative response characteristics of each detector and their respective ability to acquire qualitative andmore » quantitative information in interfering background matrices. Further, due to the unique capabilities of GC-AED, a number of dual heteroatomic (sulphur-oxygen and nitrogen-oxygen) compounds have been identified.« less

Graph Metrics of Structural Brain Networks in Individuals with Schizophrenia and Healthy Controls: Group Differences, Relationships with Intelligence, and Genetics.

PubMed

Yeo, Ronald A; Ryman, Sephira G; van den Heuvel, Martijn P; de Reus, Marcel A; Jung, Rex E; Pommy, Jessica; Mayer, Andrew R; Ehrlich, Stefan; Schulz, S Charles; Morrow, Eric M; Manoach, Dara; Ho, Beng-Choon; Sponheim, Scott R; Calhoun, Vince D

2016-02-01

One of the most prominent features of schizophrenia is relatively lower general cognitive ability (GCA). An emerging approach to understanding the roots of variation in GCA relies on network properties of the brain. In this multi-center study, we determined global characteristics of brain networks using graph theory and related these to GCA in healthy controls and individuals with schizophrenia. Participants (N=116 controls, 80 patients with schizophrenia) were recruited from four sites. GCA was represented by the first principal component of a large battery of neurocognitive tests. Graph metrics were derived from diffusion-weighted imaging. The global metrics of longer characteristic path length and reduced overall connectivity predicted lower GCA across groups, and group differences were noted for both variables. Measures of clustering, efficiency, and modularity did not differ across groups or predict GCA. Follow-up analyses investigated three topological types of connectivity--connections among high degree "rich club" nodes, "feeder" connections to these rich club nodes, and "local" connections not involving the rich club. Rich club and local connectivity predicted performance across groups. In a subsample (N=101 controls, 56 patients), a genetic measure reflecting mutation load, based on rare copy number deletions, was associated with longer characteristic path length. Results highlight the importance of characteristic path lengths and rich club connectivity for GCA and provide no evidence for group differences in the relationships between graph metrics and GCA.

Combining ability of S3 progenies for key agronomic traits in popcorn: comparison of testers in top-crosses.

PubMed

de Lima, V J; do Amaral Junior, A T; Kamphorst, S H; Pena, G F; Leite, J T; Schmitt, K F M; Vittorazzi, C; de Almeida Filho, J E; Mora, F

2016-12-02

The successful development of hybrid cultivars depends on the reliability of estimated combining ability of the parent lines. The objectives of this study were to assess the combining ability of partially inbred S 3 families of popcorn derived from the open-pollinated variety UENF 14, via top-crosses with four testers, and to compare the testers for their ability to discriminate the S 3 progenies. The experiment was conducted in the 2015/2016 crop season, in an incomplete-block (Lattice) design with three replications. The following agronomic traits were evaluated: average plant height, grain yield (GY), popping expansion (PE), and expanded popcorn volume per hectare. The top-cross hybrid, originating from the BRS-Angela vs S 3 progeny 10 combination, was indicated as promising, showing high values for specific combining ability for GY and PE. For the S 3 progenies that showed high and positive GCA values for GY and PE, the continuity of the breeding program is recommended, with the advance of self-pollination generations. Fasoulas' differentiation index discriminated the BRS-Angela tester as the most suitable for identifying the superior progenies.

Evaluation of popcorn germplasm for resistance to Sesamia nonagrioides attack.

PubMed

Butrón, A; Sandoya, G; Revilla, P; Ordás, A; Malvar, R A

2005-10-01

Popcorn adapted to Spanish conditions could be an interesting and profitable alternative to field corn. However, little is known about breeding popcorn germplasm for adaptation to Spain. Sesamia nonagrioides Lefèvbre is the main insect pest affecting popcorn quality and yield under Spanish growing conditions. The objectives of the study were the search for sources of resistance to S. nonagrioides among popcorn germplasm and to study the genetics of the resistance to S. nonagrioides attack. Eight breeding populations along with a five-inbred line diallel and two popcorn commercial checks were evaluated under S. nonagrioides infestation in 2 yr. Significant differences were found among general combining ability (GCA) effects for days to silking, S. nonagrioides tunnel length, general appearance of the ear, kernel moisture, and yield. Specific combining ability (SCA) effects were found to be significant for yield and ear damage. Therefore, heterotic patterns among popcorn materials should be taken into account to generate new popcorn hybrids that are not only more productive but also have higher kernel quality. Breeding popcorn populations BSP4APC0 and PSPW1C1 could be base germplasms in a breeding program for obtaining parental inbreds of healthy kernel popcorn hybrids. New inbred lines could be generated from the cross BP1 x BP2 that would have improved GCA and SCA effects for S. nonagrioides resistance when crossed to South American inbreds.

Combining ability analysis for within-boll yield components in upland cotton (Gossypium hirsutum L.).

PubMed

Imran, M; Shakeel, A; Azhar, F M; Farooq, J; Saleem, M F; Saeed, A; Nazeer, W; Riaz, M; Naeem, M; Javaid, A

2012-08-24

Cotton is an important cash crop worldwide, accounting for a large percentage of world agricultural exports; however, yield per acre is still poor in many countries, including Pakistan. Diallel mating system was used to identify parents for improving within-boll yield and fiber quality parameters. Combining ability analysis was employed to obtain suitable parents for this purpose. The parental genotypes CP-15/2, NIAB Krishma, CIM-482, MS-39, and S-12 were crossed in complete diallel mating under green house conditions during 2009. The F₀ seed of 20 hybrids and five parents were planted in the field in randomized complete block design with three replications during 2010. There were highly significant differences among all F₁ hybrids and their parents. Specific combining ability (SCA) variance was greater than general combining ability (GCA) variance for bolls per plant (9.987), seeds per boll (0.635), seed density (5.672), lint per seed (4.174), boll size (3.69), seed cotton yield (0.315), and lint percentage (0.470), showing predominance of non-additive genes; while seed volume (3.84) was controlled by additive gene action based on maximum GCA variance. Cultivar MS-39 was found to be the best general combiner for seed volume (0.102), seeds per boll (0.448), and lint per seed (0.038) and its utilization produced valuable hybrids, including MS-39 x NIAB Krishma and MS-39 x S-12. The parental line CIM-482 had high GCA effects for boll size (0.33) and seeds per boll (0.90). It also showed good SCA with S-12 and NIAB Krishma for bolls per plant, with CP- 15/2 for boll size, and with MS-39 for seeds per boll. The hybrids, namely, CP-15/2 x NIAB Krishma, NIAB Krishma x S-12, NIAB Krishma x CIM-482, MS-39 x NIAB Krishma, MS-39 x CP-15/2, and S-12 x MS-39 showed promising results. Correlation analysis revealed that seed cotton yield showed significant positive correlation with bolls per plant, boll size and seeds per boll while it showed negative correlation with lint percentage and lint per seed. Seed volume showed significant negative correlation with seed density. Seeds per boll were positively correlated with boll size and negatively correlated with bolls per plant lint percentage and lint per seed. Similarly, lint per seed exhibited positive correlation with lint percentage and boll size showed significantly negative correlation with bolls per plant. Presence of non-additive genetic effects in traits like bolls per plant, seeds per boll, lint per seed, seed cotton yield, and lint percentage is indicative of later generation selection or heterosis breeding may be adopted. For boll size, seed volume and seed density early generation selection may be followed because of the presence of additive gene action. The parental material used in this study and cross combinations obtained from these parents may be exploited in future breeding endeavors.

Imaging Neural Activity Using Thy1-GCaMP Transgenic mice

PubMed Central

Chen, Qian; Cichon, Joseph; Wang, Wenting; Qiu, Li; Lee, Seok-Jin R.; Campbell, Nolan R.; DeStefino, Nicholas; Goard, Michael J.; Fu, Zhanyan; Yasuda, Ryohei; Looger, Loren L.; Arenkiel, Benjamin R.; Gan, Wen-Biao; Feng, Guoping

2014-01-01

Summary The ability to chronically monitor neuronal activity in the living brain is essential for understanding the organization and function of the nervous system. The genetically encoded green fluorescent protein based calcium sensor GCaMP provides a powerful tool for detecting calcium transients in neuronal somata, processes, and synapses that are triggered by neuronal activities. Here we report the generation and characterization of transgenic mice that express improved GCaMPs in various neuronal subpopulations under the control of the Thy1 promoter. In vitro and in vivo studies show that calcium transients induced by spontaneous and stimulus-evoked neuronal activities can be readily detected at the level of individual cells and synapses in acute brain slices, as well as chronically in awake behaving animals. These GCaMP transgenic mice allow investigation of activity patterns in defined neuronal populations in the living brain, and will greatly facilitate dissecting complex structural and functional relationships of neural networks. PMID:23083733

The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): a diagnostic accuracy and cost-effectiveness study.

PubMed

Luqmani, Raashid; Lee, Ellen; Singh, Surjeet; Gillett, Mike; Schmidt, Wolfgang A; Bradburn, Mike; Dasgupta, Bhaskar; Diamantopoulos, Andreas P; Forrester-Barker, Wulf; Hamilton, William; Masters, Shauna; McDonald, Brendan; McNally, Eugene; Pease, Colin; Piper, Jennifer; Salmon, John; Wailoo, Allan; Wolfe, Konrad; Hutchings, Andrew

2016-11-01

Giant cell arteritis (GCA) is a relatively common form of primary systemic vasculitis, which, if left untreated, can lead to permanent sight loss. We compared ultrasound as an alternative diagnostic test with temporal artery biopsy, which may be negative in 9-61% of true cases. To compare the clinical effectiveness and cost-effectiveness of ultrasound with biopsy in diagnosing patients with suspected GCA. Prospective multicentre cohort study. Secondary care. A total of 381 patients referred with newly suspected GCA. Sensitivity, specificity and cost-effectiveness of ultrasound compared with biopsy or ultrasound combined with biopsy for diagnosing GCA and interobserver reliability in interpreting scan or biopsy findings. We developed and implemented an ultrasound training programme for diagnosing suspected GCA. We recruited 430 patients with suspected GCA. We analysed 381 patients who underwent both ultrasound and biopsy within 10 days of starting treatment for suspected GCA and who attended a follow-up assessment (median age 71.1 years; 72% female). The sensitivity of biopsy was 39% [95% confidence interval (CI) 33% to 46%], which was significantly lower than previously reported and inferior to ultrasound (54%, 95% CI 48% to 60%); the specificity of biopsy (100%, 95% CI 97% to 100%) was superior to ultrasound (81%, 95% CI 73% to 88%). If we scanned all suspected patients and performed biopsies only on negative cases, sensitivity increased to 65% and specificity was maintained at 81%, reducing the need for biopsies by 43%. Strategies combining clinical judgement (clinician's assessment at 2 weeks) with the tests showed sensitivity and specificity of 91% and 81%, respectively, for biopsy and 93% and 77%, respectively, for ultrasound; cost-effectiveness (incremental net monetary benefit) was £485 per patient in favour of ultrasound with both cost savings and a small health gain. Inter-rater analysis revealed moderate agreement among sonographers (intraclass correlation coefficient 0.61, 95% CI 0.48 to 0.75), similar to pathologists (0.62, 95% CI 0.49 to 0.76). There is no independent gold standard diagnosis for GCA. The reference diagnosis used to determine accuracy was based on classification criteria for GCA that include clinical features at presentation and biopsy results. We have demonstrated the feasibility of providing training in ultrasound for the diagnosis of GCA. Our results indicate better sensitivity but poorer specificity of ultrasound compared with biopsy and suggest some scope for reducing the role of biopsy. The moderate interobserver agreement for both ultrasound and biopsy indicates scope for improving assessment and reporting of test results and challenges the assumption that a positive biopsy always represents GCA. Further research should address the issue of an independent reference diagnosis, standards for interpreting and reporting test results and the evaluation of ultrasound training, and should also explore the acceptability of these new diagnostic strategies in GCA. The National Institute for Health Research Health Technology Assessment programme.

Polymyalgia rheumatica and giant cell arteritis—three challenges—consequences of the vasculitis process, osteoporosis, and malignancy

PubMed Central

Emamifar, Amir; Hess, Søren; Gerke, Oke; Hermann, Anne Pernille; Laustrup, Helle; Hansen, Per Syrak; Thye-Rønn, Peter; Marcussen, Niels; Svendstrup, Frank; Gildberg-Mortensen, Rannveig; Bang, Jacob Christian; Farahani, Ziba Ahangarani; Chrysidis, Stavros; Toftegaard, Pia; Andreasen, Rikke Asmussen; le Greves, Sebastian; Andersen, Hanne Randi; Olsen, Rudolf Nezlo; Hansen, Inger Marie Jensen

2017-01-01

Abstract Introduction: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are common inflammatory conditions. The diagnosis of PMR/GCA poses many challenges since there are no specific diagnostic tests. Recent literature emphasizes the ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to assess global disease activity in inflammatory diseases. 18F-FDG PET/CT may lead to the diagnosis at an earlier stage than conventional imaging and may also assess response to therapy. With respect to the management of PMR/GCA, there are 3 significant areas of concern as follows: vasculitis process/vascular stiffness, malignancy, and osteoporosis. Methods and analysis: All patients with suspected PMR/GCR referred to the Rheumatology section of Medicine Department at Svendborg Hospital, Denmark. The 4 separate studies in the current protocol focus on: the association of clinical picture of PMR/GCA with PET findings; the validity of 18F-FDG PET/CT scan for diagnosis of PMR/GCA compared with temporal artery biopsy; the prevalence of newly diagnosed malignancies in patients with PMR/GCA, or PMR-like syndrome, with the focus on diagnostic accuracy of 18F-FDG PET/CT scan compared with conventional workup (ie, chest X-ray/abdominal ultrasound); and the impact of disease process, and also steroid treatment on bone mineral density, body composition, and vasculitis/vascular stiffness in PMR/GCA patients. Ethics and dissemination: The study has been approved by the Regional Ethics Committee of the Region of Southern Denmark (identification number: S-20160098) and Danish Data Protection Agency (J.nr 16/40522). Results of the study will be disseminated via publications in peer-reviewed journals, and presentation at national and international conferences. PMID:28658131

What is the impact of giant cell arteritis on patients’ lives? A UK qualitative study

PubMed Central

Liddle, Jennifer; Bartlam, Roisin; Mallen, Christian D; Mackie, Sarah L; Prior, James A; Helliwell, Toby; Richardson, Jane C

2017-01-01

Objectives Clinical management of giant cell arteritis (GCA) involves balancing the risks and burdens arising from the disease with those arising from treatment, but there is little research on the nature of those burdens. We aimed to explore the impact of giant cell arteritis (GCA) and its treatment on patients’ lives. Methods UK patients with GCA participated in semi-structured telephone interviews. Inductive thematic analysis was employed. Results 24 participants were recruited (age: 65–92 years, time since diagnosis: 2 months to >6 years). The overarching themes from analysis were: ongoing symptoms of the disease and its treatment; and ‘life-changing’ impacts. The overall impact of GCA on patients’ lives arose from a changing combination of symptoms, side effects, adaptations to everyday life and impacts on sense of normality. Important factors contributing to loss of normality were glucocorticoid-related treatment burdens and fear about possible future loss of vision. Conclusions The impact of GCA in patients’ everyday lives can be substantial, multifaceted and ongoing despite apparent control of disease activity. The findings of this study will help doctors better understand patient priorities, legitimise patients’ experiences of GCA and work with patients to set realistic treatment goals and plan adaptations to their everyday lives. PMID:28838902

Diallel analysis of corn for special use as corn grits: determining the main genetic effects for corn gritting ability.

PubMed

Conrado, T V; Scapim, C A; Bignotto, L S; Pinto, R J B; Freitas, I L J; Amaral, A T; Pinheiro, A C

2014-08-26

Corn grits are used for various purposes such as flakes, snacks, livestock feed, hominy, extruded products, beer, etc. The grit size proportion varies according to the hybrid, and thus, once the use of the grits is linked to the particle size, determining the genetic effects is essential to develop hybrids for any specific use. For this purpose a complete diallel series of crosses, involving eight parents, was performed near Maringá, PR, Brazil. The objective of this study was to evaluate the general (GCA) and specific (SCA) combining abilities of 28 progeny for selection of hybrids for breeding programs and extraction of inbred lines for hybrid development. The response variables, such as plant height, ear insertion height, crop stand, grain yield, and grits, small grits and bran production, were gauged and appraised for each of the 28 progeny. The trait effects and GCA were significant for all response variables, while for SCA, only grain yield and crop stand showed significance (P < 0.05), according to Griffing (1955) analysis. A significant weak negative partial correlation was found between grain yield and grits conversion. In relation to the hybrid selection for breeding programs, the parent IAC Nelore was highly recommended for recurrent selection and the hybrids IPR 119 x HT 392 and IAC Nelore x HD 332 for the extraction of pure lines for hybrid development.

Genetic visualization with an improved GCaMP calcium indicator reveals spatiotemporal activation of the spinal motor neurons in zebrafish

PubMed Central

Muto, Akira; Ohkura, Masamichi; Kotani, Tomoya; Higashijima, Shin-ichi; Nakai, Junichi; Kawakami, Koichi

2011-01-01

Animal behaviors are generated by well-coordinated activation of neural circuits. In zebrafish, embryos start to show spontaneous muscle contractions at 17 to 19 h postfertilization. To visualize how motor circuits in the spinal cord are activated during this behavior, we developed GCaMP-HS (GCaMP-hyper sensitive), an improved version of the genetically encoded calcium indicator GCaMP, and created transgenic zebrafish carrying the GCaMP-HS gene downstream of the Gal4-recognition sequence, UAS (upstream activation sequence). Then we performed a gene-trap screen and identified the SAIGFF213A transgenic fish that expressed Gal4FF, a modified version of Gal4, in a subset of spinal neurons including the caudal primary (CaP) motor neurons. We conducted calcium imaging using the SAIGFF213A; UAS:GCaMP-HS double transgenic embryos during the spontaneous contractions. We demonstrated periodic and synchronized activation of a set of ipsilateral motor neurons located on the right and left trunk in accordance with actual muscle movements. The synchronized activation of contralateral motor neurons occurred alternately with a regular interval. Furthermore, a detailed analysis revealed rostral-to-caudal propagation of activation of the ipsilateral motor neuron, which is similar to but much slower than the rostrocaudal delay observed during swimming in later stages. Our study thus demonstrated coordinated activities of the motor neurons during the first behavior in a vertebrate. We propose the GCaMP technology combined with the Gal4FF-UAS system is a powerful tool to study functional neural circuits in zebrafish. PMID:21383146

Breeding maize for resistance to ear rot caused by Fusarium moniliforme.

PubMed

Hefny, M; Attaa, S; Bayoumi, T; Ammar, S; El-Bramawy, M

2012-01-15

Maize ear rots are among the most important impediments to increased maize production in Egypt. The present research was conducted to estimate combining abilities, heterosis and correlation coefficients for resistance to ear rot disease in seven corn inbred lines and their 21 crosses under field conditions. Results demonstrated that both additive and non-additive gene actions were responsible for the genetic expression of all characters with the preponderance of non-additive actions for days to 50% silking. The parental line L51 was the best combiner for earliness, low infection severity %, high phenols content, short plants and reasonable grain yield, while L101 was good combiner for low ear rot infection only. The cross: L122 x L84, L122 x L101, L51 x L101, L76 x L36, L76 x L84, L36 x L84, L36 x L81 and L36 x L101 which involved one or both parents with good General Combining Ability (GCA) effects expressed useful significant heterosis and Specific Combining Ability (SCA) effects for low infection severity %, high phenol contents, early silking, tall plants and high grain yield. Phenotypic and genotypic correlation coefficients suggest that selection for resistance to ear rot should identify lines with high yielding ability, early silking, tall plants, high phenols content and chitinase activity.

Vasodilator therapy with hydralazine induces angiotensin AT2 receptor-mediated cardiomyocyte growth in mice lacking guanylyl cyclase-A

PubMed Central

Li, Y; Saito, Y; Kuwahara, K; Rong, X; Kishimoto, I; Harada, M; Horiuchi, M; Murray, M; Nakao, K

2010-01-01

Background and purpose: Recent clinical guidelines advocate the use of the isosorbide dinitrate/hydralazine combination in treatment for heart failure. However, clinical and laboratory evidence suggest that some vasodilators may induce cardiac hypertrophy under uncertain conditions. This study investigated the effects and underlying mechanism of action of the vasodilator hydralazine on cardiac growth. Experimental approach: Wild-type mice and animals deficient in guanylyl cyclase-A (GCA) and/or angiotensin receptors (AT1 and AT2 subtypes) were treated with hydralazine (≈24 mg·kg−1·day−1 in drinking water) for 5 weeks. Cardiac mass and/or cardiomyocyte cross-sectional area, fibrosis (van Giessen-staining) and cardiac gene expression (real-time RT-PCR) were measured. Key results: Hydralazine lowered blood pressure in mice of all genotypes. However, this treatment increased the heart and left ventricular to body weight ratios, as well as cardiomyocyte cross-sectional area, and cardiac expression of atrial natriuretic peptide mRNA in mice lacking GCA. Hydralazine did not affect cardiac hypertrophy in wild-type mice and mice lacking either AT1 or AT2 receptors alone. However, the pro-hypertrophic effect of hydralazine was prevented in mice lacking both GCA and AT2, but not GCA and AT1 receptors. However, hydralazine did decrease cardiac collagen deposition and collagen I mRNA (signs of cardiac fibrosis) in mice that were deficient in GCA, or both GCA and AT2 receptors. Conclusions and implications: The vasodilator hydralazine induced AT2 receptor-mediated cardiomyocyte growth under conditions of GCA deficiency. However, attenuation of cardiac fibrosis by hydralazine could be beneficial in the management of cardiac diseases. PMID:20136844

Fronto-Parietal gray matter and white matter efficiency differentially predict intelligence in males and females.

PubMed

Ryman, Sephira G; Yeo, Ronald A; Witkiewitz, Katie; Vakhtin, Andrei A; van den Heuvel, Martijn; de Reus, Marcel; Flores, Ranee A; Wertz, Christopher R; Jung, Rex E

2016-11-01

While there are minimal sex differences in overall intelligence, males, on average, have larger total brain volume and corresponding regional brain volumes compared to females, measures that are consistently related to intelligence. Limited research has examined which other brain characteristics may differentially contribute to intelligence in females to facilitate equal performance on intelligence measures. Recent reports of sex differences in the neural characteristics of the brain further highlight the need to differentiate how the structural neural characteristics relate to intellectual ability in males and females. The current study utilized a graph network approach in conjunction with structural equation modeling to examine potential sex differences in the relationship between white matter efficiency, fronto-parietal gray matter volume, and general cognitive ability (GCA). Participants were healthy adults (n = 244) who completed a battery of cognitive testing and underwent structural neuroimaging. Results indicated that in males, a latent factor of fronto-parietal gray matter was significantly related to GCA when controlling for total gray matter volume. In females, white matter efficiency and total gray matter volume were significantly related to GCA, with no specificity of the fronto-parietal gray matter factor over and above total gray matter volume. This work highlights that different neural characteristics across males and females may contribute to performance on intelligence measures. Hum Brain Mapp 37:4006-4016, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Efficiency of Lasers and a Desensitizer Agent on Dentin Hypersensitivity Treatment: A Clinical Study.

PubMed

Ozlem, K; Esad, G M; Ayse, A; Aslihan, U

2018-02-01

The aim of this clinical study was to determine and compare the efficiency of the glutaraldehyde-containing agent (GCA), Nd:YAG, Er,Cr:YSGG lasers, and the combination of them on the dentin hypersensitivity (DH) treatment. This study was performed with the participation of 17 healthy adult patients having 100 teeth with DH; the patients were randomly divided into five groups according to the treatment protocol: (1) application of GCA on sensitive teeth, (2) Nd:YAG laser (1 W/cm 2 , 10 Hz) irradiation on sensitive teeth, (3) application of GCA on sensitive teeth and then Nd:YAG laser irradiation, (4) Er,Cr:YSGG laser (0.25 W/cm 2 , 20 Hz) irradiation on sensitive teeth, (5) application of GCA on sensitive teeth and then Er,Cr:YSGG laser irradiation. Sensitivity levels were assessed by the Yeaple probe on the buccal surfaces of the teeth at a force setting of 10 g. Measurements were performed for 30 min, after 7, 90, and 180 days of the therapy to assess the effects of desensitization. The evaluations were analyzed using the one-way analysis of variance and repeated measurement test (P < 0.05). After sessions, DH was significantly reduced in all groups at each measurement point. The Er,Cr:YSGG laser with or without GCA application were the most effective ones in DH treatment (P < 0.05). Comparison of the treatment regimens demonstrated that the scores achieved with the Yeaple probe were not significantly higher for the Nd:YAG laser groups than the GCA alone group. This clinical study shows that the Er,Cr:YSGG laser have promising potential for the treatment of DH.

Polanyi Evaluation of Adsorptive Capacities of Commercial Activated Carbons

NASA Technical Reports Server (NTRS)

Monje, Oscar; Surma, Jan M.

2017-01-01

Commercial activated carbons from Calgon (207C and OVC) and Cabot Norit (RB2 and GCA 48) were evaluated for use in spacecraft trace contaminant control filters. The Polanyi potential plots of the activated carbons were compared using to those of Barnebey-Cheney Type BD, an untreated activated carbon with similar properties as the acid-treated Barnebey-Sutcliffe Type 3032 utilized in the TCCS. Their adsorptive capacities under dry conditions were measured in a closed loop system and the sorbents were ranked for their ability to remove common VOCs found in spacecraft cabin air. This comparison suggests that these sorbents can be ranked as GCA 48 207C, OVC RB2 for the compounds evaluated.

Association of vascular physical examination findings and arteriographic lesions in large vessel vasculitis.

PubMed

Grayson, Peter C; Tomasson, Gunnar; Cuthbertson, David; Carette, Simon; Hoffman, Gary S; Khalidi, Nader A; Langford, Carol A; McAlear, Carol A; Monach, Paul A; Seo, Philip; Warrington, Kenneth J; Ytterberg, Steven R; Merkel, Peter A

2012-02-01

To assess the utility of the vascular physical examination to detect arteriographic lesions in patients with established large vessel vasculitis (LVV), including Takayasu's arteritis (TAK) and giant cell arteritis (GCA). In total, 100 patients (TAK = 68, GCA = 32) underwent standardized physical examination and angiography of the carotid, subclavian, and axillary arteries. Sensitivity and specificity were calculated for the association between findings on physical examination focusing on the vascular system (absent pulse, bruit, and blood pressure difference) and arteriographic lesions defined as stenosis, occlusion, or aneurysm. We found 67% of patients had at least 1 abnormality on physical examination (74% TAK, 53% GCA). Arteriographic lesions were seen in 76% of patients (82% TAK, 63% GCA). Individual physical examination findings had poor sensitivity (range 14%-50%) and good-excellent specificity (range 71%-98%) to detect arteriographic lesions. Even when considering physical examination findings in combination, at least 30% of arteriographic lesions were missed. Specificity improved (range 88%-100%) if individual physical examination findings were compared to a broader region of vessels rather than specific anatomically correlated vessels and if ≥ 1 physical examination findings were combined. In patients with established LVV, physical examination alone is worthwhile to detect arterial disease but does not always localize or reveal the full extent of arteriographic lesions. Abnormal vascular system findings on physical examination are highly associated with the presence of arterial lesions, but normal findings on physical examination do not exclude the possibility of arterial disease. Serial angiographic assessment is advisable to monitor arterial disease in patients with established LVV.

Genome-wide association study of esophageal squamous cell carcinoma in Chinese subjects identifies susceptibility loci at PLCE1 and C20orf54.

PubMed

Wang, Li-Dong; Zhou, Fu-You; Li, Xue-Min; Sun, Liang-Dan; Song, Xin; Jin, Yan; Li, Jiang-Man; Kong, Guo-Qiang; Qi, Hong; Cui, Juan; Zhang, Lian-Qun; Yang, Jie-Zhi; Li, Ji-Lin; Li, Xing-Chuan; Ren, Jing-Li; Liu, Zhi-Cai; Gao, Wen-Jun; Yuan, Ling; Wei, Wu; Zhang, Yan-Rui; Wang, Wei-Peng; Sheyhidin, Ilyar; Li, Feng; Chen, Bao-Ping; Ren, Shu-Wei; Liu, Bin; Li, Dan; Ku, Jian-Wei; Fan, Zong-Min; Zhou, Sheng-Li; Guo, Zhi-Gang; Zhao, Xue-Ke; Liu, Na; Ai, Yong-Hong; Shen, Fang-Fang; Cui, Wen-Yan; Song, Shuang; Guo, Tao; Huang, Jing; Yuan, Chao; Huang, Jia; Wu, Yue; Yue, Wen-Bin; Feng, Chang-Wei; Li, Hong-Lei; Wang, Yan; Tian, Jin-Ya; Lu, Yue; Yuan, Yi; Zhu, Wen-Liang; Liu, Min; Fu, Wen-Jing; Yang, Xia; Wang, Han-Jing; Han, Suo-Li; Chen, Jie; Han, Min; Wang, Hai-Yan; Zhang, Peng; Li, Xiu-Min; Dong, Jin-Cheng; Xing, Guo-Lan; Wang, Ran; Guo, Ming; Chang, Zhi-Wei; Liu, Hai-Lin; Guo, Li; Yuan, Zhi-Qing; Liu, Hai; Lu, Qin; Yang, Liu-Qin; Zhu, Fu-Guo; Yang, Xiu-Feng; Feng, Xiao-Shan; Wang, Zhou; Li, Yin; Gao, She-Gan; Qige, Qirenwang; Bai, Long-Tang; Yang, Wen-Jun; Lei, Guang-Yan; Shen, Zhong-Ying; Chen, Long-Qi; Li, En-Min; Xu, Li-Yan; Wu, Zhi-Yong; Cao, Wei-Ke; Wang, Jian-Po; Bao, Zhi-Qin; Chen, Ji-Li; Ding, Guang-Cheng; Zhuang, Xiang; Zhou, Ying-Fa; Zheng, Hou-Feng; Zhang, Zheng; Zuo, Xian-Bo; Dong, Zi-Ming; Fan, Dong-Mei; He, Xin; Wang, Jin; Zhou, Qi; Zhang, Qin-Xian; Jiao, Xin-Ying; Lian, Shi-Yong; Ji, Ai-Fang; Lu, Xiao-Mei; Wang, Jin-Sheng; Chang, Fu-Bao; Lu, Chang-Dong; Chen, Zhi-Guo; Miao, Jian-Jun; Fan, Zeng-Lin; Lin, Ruo-Bai; Liu, Tai-Jiang; Wei, Jin-Chang; Kong, Qing-Peng; Lan, Yu; Fan, Yu-Jing; Gao, Fu-Sheng; Wang, Tian-Yun; Xie, Dong; Chen, Shu-Qing; Yang, Wan-Cai; Hong, Jun-Yan; Wang, Liang; Qiu, Song-Liang; Cai, Zhi-Ming; Zhang, Xue-Jun

2010-09-01

We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.

Association of Vascular Physical Examination Findings and Arteriographic Lesions in Large Vessel Vasculitis

PubMed Central

GRAYSON, PETER C.; TOMASSON, GUNNAR; CUTHBERTSON, DAVID; CARETTE, SIMON; HOFFMAN, GARY S.; KHALIDI, NADER A.; LANGFORD, CAROL A.; McALEAR, CAROL A.; MONACH, PAUL A.; SEO, PHILIP; WARRINGTON, KENNETH J.; YTTERBERG, STEVEN R.; MERKEL, PETER A.

2013-01-01

Objective To assess the utility of the vascular physical examination to detect arteriographic lesions in patients with established large vessel vasculitis (LVV), including Takayasu’s arteritis (TAK) and giant cell arteritis (GCA). Methods In total, 100 patients (TAK = 68, GCA = 32) underwent standardized physical examination and angiography of the carotid, subclavian, and axillary arteries. Sensitivity and specificity were calculated for the association between findings on physical examination focusing on the vascular system (absent pulse, bruit, and blood pressure difference) and arteriographic lesions defined as stenosis, occlusion, or aneurysm. Results We found 67% of patients had at least 1 abnormality on physical examination (74% TAK, 53% GCA). Arteriographic lesions were seen in 76% of patients (82% TAK, 63% GCA). Individual physical examination findings had poor sensitivity (range 14%–50%) and good-excellent specificity (range 71%–98%) to detect arteriographic lesions. Even when considering physical examination findings in combination, at least 30% of arteriographic lesions were missed. Specificity improved (range 88%–100%) if individual physical examination findings were compared to a broader region of vessels rather than specific anatomically correlated vessels and if ≥ 1 physical examination findings were combined. Conclusion In patients with established LVV, physical examination alone is worthwhile to detect arterial disease but does not always localize or reveal the full extent of arteriographic lesions. Abnormal vascular system findings on physical examination are highly associated with the presence of arterial lesions, but normal findings on physical examination do not exclude the possibility of arterial disease. Serial angiographic assessment is advisable to monitor arterial disease in patients with established LVV. PMID:22174204

Diallel crosses for resistance to Macrophomina phaseolina and Thanatephorus cucumeris on cowpea.

PubMed

Lima, L R L; Damasceno-Silva, K J; Noronha, M A; Schurt, D A; Rocha, M M

2017-09-27

This study aimed at identifying and selecting through partial diallel analysis, segregating populations of cowpea resistant to Macrophomina phaseolina and Thanatephorus cucumeris, based on the evaluation of general (GCA) and specific combining ability (SCA), involved in the genetic control of resistance. For this reason, 19 grouped cowpea genotypes, considering the resistance to these pathogens, were crossed in partial diallel scheme 14 x 5, during 2013 and 2014. The 70 F 2 populations and the 19 parents were evaluated in a greenhouse as the reaction to pathogens, separately. The diallel analysis was performed according to the model of partial diallel proposed by Geraldi and Miranda Filho (1988). The additive effects predominated in the genetic control of the traits severity of charcoal rot (SEV) and area under the disease progress curve (AUDPC) to web blight, enabling the achievement of genetic gain with selection of resistant strains. Analyzing the effects of GCA, the parents BR 14-Mulato, BRS Tumucumaque and BRS Guariba, have a higher concentration of favorable alleles, highlighting, according to the values of SCA, the combinations BR 14-Mulato x MNC02-675F-4-10, BRS Tumucumaque x IT98K-1092-1, BRS Tumucumaque x MNC02-675F-4-10, BRS Tumucumaque x MNC02-675F-9-2, BRS Guariba x IT98K-1092-1, BRS Guariba x MNC02-675F-4-9, and BRS Guariba x MNC02-675F-4-10, as the most promising and indicated to obtain lines resistant to M. phaseolina and T. cucumeris in cowpea, simultaneously.

Does herpes zoster predispose to giant cell arteritis: a geo-epidemiologic study.

PubMed

Ing, Edsel B; Ing, Royce; Liu, Xinyang; Zhang, Angela; Torun, Nurhan; Sey, Michael; Pagnoux, Christian

2018-01-01

Giant cell arteritis (GCA) is the most common systemic vasculitis in the elderly and can cause irreversible blindness and aortitis. Varicella zoster (VZ), which is potentially preventable by vaccination, has been proposed as a possible immune trigger for GCA, but this is controversial. The incidence of GCA varies widely by country. If VZ virus contributes to the immunopathogenesis of GCA we hypothesized that nations with increased incidence of GCA would also have increased incidence of herpes zoster (HZ). We conducted an ecologic analysis to determine the relationship between the incidence of HZ and GCA in different countries. A literature search for the incidence rates (IRs) of GCA and HZ from different countries was conducted. Correlation and linear regression was performed comparing the disease IR of each country for subjects 50 years of age or older. We found the IR for GCA and HZ from 14 countries. Comparing the IRs for GCA and HZ in 50-year-olds, the Pearson product-moment correlation ( r ) was -0.51, with linear regression coefficient (β) -2.92 (95% CI -5.41, -0.43; p =0.025) using robust standard errors. Comparing the IRs for GCA and HZ in 70-year-olds, r was -0.40, with β -1.78, which was not statistically significant (95% CI -4.10, 0.53; p =0.12). Although this geo-epidemiologic study has potential for aggregation and selection biases, there was no positive biologic gradient between the incidence of clinically evident HZ and GCA.

Trophic structure of mesopelagic fishes in the Gulf of Mexico revealed by gut content and stable isotope analyses

USGS Publications Warehouse

McClain-Counts, Jennifer P.; Demopoulos, Amanda W.J.; Ross, Steve W.

2017-01-01

Mesopelagic fishes represent an important component of the marine food web due to their global distributions, high abundances and ability to transport organic material throughout a large part of the water column. This study combined stable isotope (SIAs) and gut content analyses (GCAs) to characterize the trophic structure of mesopelagic fishes in the North-Central Gulf of Mexico. Additionally, this study examined whether mesopelagic fishes utilized chemosynthetic energy from cold seeps. Specimens were collected (9–25 August 2007) over three deep (>1,000 m) cold seeps at discrete depths (surface to 1,503 m) over the diurnal cycle. GCA classified 31 species (five families) of mesopelagic fishes into five feeding guilds: piscivores, large crustacean consumers, copepod consumers, generalists and mixed zooplanktivores. However, these guilds were less clearly defined based on stable isotope mixing model (MixSIAR) results, suggesting diets may be more mixed over longer time periods (weeks–months) and across co-occurring species. Copepods were likely important for the majority of mesopelagic fishes, consistent with GCA (this study) and previous literature. MixSIAR results also identified non-crustacean prey items, including salps and pteropods, as potentially important prey items for mesopelagic fishes, including those fishes not analysed in GCA (Sternoptyx spp. and Melamphaidae). Salps and other soft-bodied species are often missed in GCAs. Mesopelagic fishes had δ13C results consistent with particulate organic matter serving as the baseline organic carbon source, fueling up to three trophic levels. Fishes that undergo diel vertical migration were depleted in 15N relative to weak migrators, consistent with depth-specific isotope trends in sources and consumers, and assimilation of 15N-depleted organic matter in surface waters. Linear correlations between fish size and δ15N values suggested ontogenetic changes in fish diets for several species. While there was no direct measure of mesopelagic fishes assimilating chemosynthetic material, detection of infrequent consumption of this food resource may be hindered by the assimilation of isotopically enriched photosynthetic organic matter. By utilizing multiple dietary metrics (e.g. GCA, δ13C, δ15N, MixSIAR), this study better defined the trophic structure of mesopelagic fishes and allowed for insights on feeding, ultimately providing useful baseline information from which to track mesopelagic trophodynamics over time and space.

The CAA repeat polymorphism in the ZFHX3 gene is associated with risk of coronary heart disease in a Chinese population.

PubMed

Sun, Shunchang; Zhang, Wenwu; Chen, Xi; Song, Huiwen

2015-04-01

Coronary heart disease (CHD) is a disease resulting from the interaction between genetic variations and environmental factors. Zinc finger homeobox 3 (ZFHX3) is a transcription factor and contains a poly-glutamine tract in a compositionally biased region that is encoded by exon 9, containing a cluster of CAG and CAA triplets followed by the polymorphic CAA repeats: (CAG)2(CAA)2(CAG)3CAACAG(CAA)nGCA. Thus, nine successive glutamine residues precede the poly-glutamine tract, encoded by the polymorphic CAA repeats. The aim of this study was to investigate the association of the CAA repeat polymorphism in exon 9 of the ZFHX3 gene with the risk of CHD in a Chinese population. The CAA repeat polymorphism was determined by polymerase chain reaction followed by DNA sequencing in 321 CHD patients. Genotype frequencies were compared using the non-parametric mood median test. Four alleles of CAG(CAA)10GCA, CAG(CAA)8GCA, CAG(CAA)9GCA, and CAG(CAA)11GCA were found in Chinese CHD patients in exon 9 of the ZFHX3 gene. The CAG(CAA)10GCA was a major allele (95.95%), and the CAG(CAA)8GCA was a minor allele (3.58%). The CAG(CAA)9GCA and CAG(CAA)11GCA were rare alleles (0.31% and 0.16%). The CAG(CAA)10GCA allele encodes a poly-glutamine tract of 19 residues. Importantly, the CHD patients homozygous for the CAG(CAA)10GCA allele had a higher risk of CHD, compared to the heterozygous patients carrying a CAG(CAA)8GCA allele. Moreover, the CAG(CAA)10GCA allele was significantly associated with hypertension, diabetes mellitus, or dyslipidemia (P < 0.05). Thus, the CAA repeat polymorphism in exon 9 of the ZFHX3 gene contributes to the CHD susceptibility in the Chinese population.

Does herpes zoster predispose to giant cell arteritis: a geo-epidemiologic study

PubMed Central

Ing, Edsel B; Ing, Royce; Liu, Xinyang; Zhang, Angela; Torun, Nurhan; Sey, Michael; Pagnoux, Christian

2018-01-01

Purpose Giant cell arteritis (GCA) is the most common systemic vasculitis in the elderly and can cause irreversible blindness and aortitis. Varicella zoster (VZ), which is potentially preventable by vaccination, has been proposed as a possible immune trigger for GCA, but this is controversial. The incidence of GCA varies widely by country. If VZ virus contributes to the immunopathogenesis of GCA we hypothesized that nations with increased incidence of GCA would also have increased incidence of herpes zoster (HZ). We conducted an ecologic analysis to determine the relationship between the incidence of HZ and GCA in different countries. Methods A literature search for the incidence rates (IRs) of GCA and HZ from different countries was conducted. Correlation and linear regression was performed comparing the disease IR of each country for subjects 50 years of age or older. Results We found the IR for GCA and HZ from 14 countries. Comparing the IRs for GCA and HZ in 50-year-olds, the Pearson product-moment correlation (r) was −0.51, with linear regression coefficient (β) −2.92 (95% CI −5.41, −0.43; p=0.025) using robust standard errors. Comparing the IRs for GCA and HZ in 70-year-olds, r was −0.40, with β −1.78, which was not statistically significant (95% CI −4.10, 0.53; p=0.12). Conclusion Although this geo-epidemiologic study has potential for aggregation and selection biases, there was no positive biologic gradient between the incidence of clinically evident HZ and GCA. PMID:29391771

Varicella zoster virus in the temporal artery of a patient with giant cell arteritis.

PubMed

Nagel, Maria A; Khmeleva, Nelly; Boyer, Philip J; Choe, Alexander; Bert, Robert; Gilden, Don

2013-12-15

We recently detected varicella zoster virus (VZV) in the temporal arteries (TA) of 5/24 patients with clinically suspect giant cell arteritis (GCA) whose TAs were GCA-negative pathologically; in those GCA-negative, VZV+TAs, virus antigen predominated in the arterial adventitia, but without medial necrosis and multinucleated giant cells. During our continuing search for VZV antigen in GCA-negative TAs, in the TA of one subject, we found abundant VZV antigen, as well as VZV DNA, in multiple regions (skip areas) of the TA spanning 350 μm, as well as in skeletal muscle adjacent to the infected TA. Additional pathological analysis of sections adjacent to those containing viral antigen revealed inflammation involving the arterial media and abundant multinucleated giant cells characteristic of GCA. Detection of VZV in areas of the TA with pathological features of GCA warrants further correlative pathological-virological analysis of VZV in GCA. © 2013.

Unraveling Synaptic GCaMP Signals: Differential Excitability and Clearance Mechanisms Underlying Distinct Ca2+ Dynamics in Tonic and Phasic Excitatory, and Aminergic Modulatory Motor Terminals in Drosophila

PubMed Central

Xing, Xiaomin

2018-01-01

Abstract GCaMP is an optogenetic Ca2+ sensor widely used for monitoring neuronal activities but the precise physiological implications of GCaMP signals remain to be further delineated among functionally distinct synapses. The Drosophila neuromuscular junction (NMJ), a powerful genetic system for studying synaptic function and plasticity, consists of tonic and phasic glutamatergic and modulatory aminergic motor terminals of distinct properties. We report a first simultaneous imaging and electric recording study to directly contrast the frequency characteristics of GCaMP signals of the three synapses for physiological implications. Different GCaMP variants were applied in genetic and pharmacological perturbation experiments to examine the Ca2+ influx and clearance processes underlying the GCaMP signal. Distinct mutational and drug effects on GCaMP signals indicate differential roles of Na+ and K+ channels, encoded by genes including paralytic (para), Shaker (Sh), Shab, and ether-a-go-go (eag), in excitability control of different motor terminals. Moreover, the Ca2+ handling properties reflected by the characteristic frequency dependence of the synaptic GCaMP signals were determined to a large extent by differential capacity of mitochondria-powered Ca2+ clearance mechanisms. Simultaneous focal recordings of synaptic activities further revealed that GCaMPs were ineffective in tracking the rapid dynamics of Ca2+ influx that triggers transmitter release, especially during low-frequency activities, but more adequately reflected cytosolic residual Ca2+ accumulation, a major factor governing activity-dependent synaptic plasticity. These results highlight the vast range of GCaMP response patterns in functionally distinct synaptic types and provide relevant information for establishing basic guidelines for the physiological interpretations of presynaptic GCaMP signals from in situ imaging studies. PMID:29464198

Infections and the risk of incident giant cell arteritis: a population-based, case-control study.

PubMed

Rhee, Rennie L; Grayson, Peter C; Merkel, Peter A; Tomasson, Gunnar

2017-06-01

Alterations in the immune system and infections are suspected to increase susceptibility to giant cell arteritis (GCA). Recently herpes zoster has been directly implicated in the pathogenesis of GCA. We examined the association between prior infections, in particular herpes zoster, and incident GCA in a population-based cohort. A nested case-control study was performed using an electronic database from the UK. Cases with newly diagnosed GCA were identified using a validated algorithm and compared with age-matched, sex-matched and practice-matched controls. Conditional logistic regression was used to examine the relationship between any infection or herpes zoster infection on the development of GCA after adjusting for potential confounders; results were expressed as incidence rate ratios (IRRs). There were 4559 cases of GCA and 22 795 controls. Any prior infection and herpes zoster were associated with incident GCA (IRR 1.26 (95% CI 1.16 to 1.36), p<0.01; and 1.17 (95% CI 1.04 to 1.32), p<0.01, respectively). A greater number of infections was associated with a higher risk of developing GCA (IRR for 1, 2-4 and ≥5 infections was 1.28, 1.60 and 2.18, respectively). Antecedent infections and, to a lesser extent, herpes zoster infections are modestly associated with incident GCA. These data provide population-level support for the hypothesis that long-standing alterations of the immune system are associated with susceptibility to GCA and suggest that herpes zoster is unlikely to play a major causal role in the pathogenesis of GCA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Retrospective, Multicenter Comparison of the Clinical Presentation of Patients Presenting With Diplopia From Giant Cell Arteritis vs Other Causes.

PubMed

Ross, Ahmara G; Jivraj, Imran; Rodriguez, Geoffrey; Pistilli, Maxwell; Chen, John J; Sergott, Robert C; Moster, Mark; Sheldon, Claire A; Liu, Grant T; Foroozan, Rod; Ko, Melissa W; Francis, Courtney E; Williams, Zoë R; Lee, Andrew G; McClelland, Collin M; Shindler, Kenneth S; Yalamanchili, Sushma; Osborne, Benjamin; Hedges, Thomas R; Van Stavern, Gregory P; Puckett, Ernest; Rigi, Mohammed; García-Basterra, Ignacia; Tamhankar, Madhura A

2018-04-24

Although giant cell arteritis (GCA) is a well-known cause of transient and permanent vision loss, diplopia as a presenting symptom of this condition is uncommon. We compared symptoms and signs of patients presenting with diplopia from GCA to those from other causes. This was a multicenter, retrospective study comparing the clinical characteristics of patients presenting with diplopia from GCA with age-matched controls. Demographic information, review of symptoms, ophthalmic examination, and laboratory data of biopsy-proven patients with GCA were compared with those of age-matched controls presenting with diplopia. A total of 27 patients presented with diplopia from GCA, 19 with constant diplopia, and 8 with transient diplopia. All patients with constant diplopia from GCA were matched with 67 control subjects who had diplopia from other etiologies. Patients with GCA were more likely to describe other accompanying visual symptoms (58% vs 25%, P = 0.008), a greater number of systemic GCA symptoms (3.5, GCA vs 0.6, controls, P < 0.001) such as headache (94% [17/18] vs 39% [23/67]; P < 0.001), jaw claudication (80% [12/15] vs 0% [0/36]; P < 0.001), and scalp tenderness (44% [7/16] vs 7% [3/43]; P < 0.001). Ocular ischemic lesions (26% vs 1%, P < 0.001) were also common in patients with diplopia from GCA. Inflammatory markers were elevated significantly in patients with GCA vs controls (erythrocyte sedimentation rate: 91% [10/11] vs 12% [3/25], P < 0.001; C-reactive protein: 89% [8/9] vs 11% [2/19], P < 0.001). GCA is a rare but serious cause of diplopia among older adults and must be differentiated from other more common benign etiologies. Our study suggests that most patients with diplopia from GCA have concerning systemic symptoms and/or elevated inflammatory markers that should trigger further work-up. Moreover, careful ophthalmoscopic examination should be performed to look for presence of ocular ischemic lesions in older patients presenting with acute diplopia.

Associations between polymyalgia rheumatica and giant cell arteritis and 12 cardiovascular diseases.

PubMed

Pujades-Rodriguez, Mar; Duyx, Bram; Thomas, Sara L; Stogiannis, Dimitris; Smeeth, Liam; Hemingway, Harry

2016-03-01

Evidence of the association of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) with the full range of cardiovascular diseases (CVDs) is limited. We examined their relationship with the first clinical presentation of the 12 most common CVDs in an unselected population-based cohort of men and women. We analysed CArdiovascular disease research using LInked Bespoke studies and Electronic health Records (CALIBER) data, which links primary care and hospital and mortality data in England, from 1997 to 2010. We assembled a cohort of men and women initially free from CVD at baseline and included all patients with PMR and/or GCA (PMR/GCA) diagnosis, matched by age, sex and general practice with up to 10 individuals without PMR/GCA. Random effects Poisson regression analysis was used to study the association between PMR/GCA and the initial presentation of 12 types of CVDs. The analysis included 9776 patients with PMR only, 1164 with GCA only, 627 with PMR and GCA and 105 504 without either condition. During a median of 3.14 years of follow-up 2787 (24.1%) individuals with PMR/GCA and 21 559 (20.4%) without PMR/GCA developed CVDs. Patients with PMR/GCA had lower rates of unheralded coronary death (3.18 vs 3.61/1000 person-years; adjusted incidence ratio 0.79, 95% CI 0.66 to 0.95), transient ischaemic attack (5.11 vs 5.61/1000 person-years; 0.67, 95% CI 0.54 to 0.84) and coronary and death composite (24.17 vs 25.80/1000 person-years; 0.90, 95% CI 0.82 to 0.98). No associations were observed for other CVDs or cerebrovascular diseases, and in patients with only PMR or GCA. No evidence of interaction by age or sex was found. Estimates decreased with longer PMR/GCA duration and findings were robust to multiple sensitivity analyses. In this large contemporary population-based cohort the presence of PMR and/or GCA was not associated with an increased risk of CVDs or cerebrovascular diseases regardless of PMR/GCA duration. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Diallel Analysis and Growth Parameters as Selection Tools for Drought Tolerance in Young Theobroma cacao Plants

PubMed Central

dos Santos, Emerson Alves; de Almeida, Alex-Alan Furtado; Ahnert, Dario; Branco, Marcia Christina da Silva; Valle, Raúl René; Baligar, Virupax C.

2016-01-01

This study aimed to estimate the combining ability, of T. cacao genotypes preselected for drought tolerance through diallel crosses. The experiment was conducted under greenhouse conditions at the Cacao Research Center (CEPEC), Ilhéus, Bahia, Brazil, in a completely randomized block design, in an experimental arrangement 21 x 2 [21 complete diallel crosses and two water regimes (control and stressed)]. In the control, soil moisture was kept close to field capacity, with predawn leaf water potential (ΨWL) ranging from -0.1 to -0.5 MPa. In the drought regime, the soil moisture was reduced gradually by decreasing the amount of water application until ΨWL reached -2.0 to -2.5 MPa. Significant differences (p < 0.05) were observed for most morphological attributes analyzed regarding progenies, water regime and their interactions. The results of the joint diallel analysis revealed significant effects between general combining ability (GCA) x water regimes and between specific combining ability (SCA) x water regimes. The SCA 6 genetic material showed high general combining ability for growth variables regardless of the water regime. In general, the water deficit influenced the production of biomass in most of the evaluated T. cacao crosses, except for SCA-6 x IMC-67, Catongo x SCA, MOC-01 x Catongo, Catongo x IMC-67 and RB-40 x Catongo. Multivariate analysis showed that stem diameter (CD), total leaf area (TLA), leaf dry biomass (LDB), stem dry biomass (SDB), root dry biomass (RDB), total dry biomass (TDB), root length (RL), root volume (RV), root diameter (RD) <1 mm and 1 <(RD) <2 mm were the most important growth parameters in the separation of T. cacao genotypes in to tolerant and intolerant to soil water deficit. PMID:27504627

Diallel Analysis and Growth Parameters as Selection Tools for Drought Tolerance in Young Theobroma cacao Plants.

PubMed

Dos Santos, Emerson Alves; Almeida, Alex-Alan Furtado de; Ahnert, Dario; Branco, Marcia Christina da Silva; Valle, Raúl René; Baligar, Virupax C

2016-01-01

This study aimed to estimate the combining ability, of T. cacao genotypes preselected for drought tolerance through diallel crosses. The experiment was conducted under greenhouse conditions at the Cacao Research Center (CEPEC), Ilhéus, Bahia, Brazil, in a completely randomized block design, in an experimental arrangement 21 x 2 [21 complete diallel crosses and two water regimes (control and stressed)]. In the control, soil moisture was kept close to field capacity, with predawn leaf water potential (ΨWL) ranging from -0.1 to -0.5 MPa. In the drought regime, the soil moisture was reduced gradually by decreasing the amount of water application until ΨWL reached -2.0 to -2.5 MPa. Significant differences (p < 0.05) were observed for most morphological attributes analyzed regarding progenies, water regime and their interactions. The results of the joint diallel analysis revealed significant effects between general combining ability (GCA) x water regimes and between specific combining ability (SCA) x water regimes. The SCA 6 genetic material showed high general combining ability for growth variables regardless of the water regime. In general, the water deficit influenced the production of biomass in most of the evaluated T. cacao crosses, except for SCA-6 x IMC-67, Catongo x SCA, MOC-01 x Catongo, Catongo x IMC-67 and RB-40 x Catongo. Multivariate analysis showed that stem diameter (CD), total leaf area (TLA), leaf dry biomass (LDB), stem dry biomass (SDB), root dry biomass (RDB), total dry biomass (TDB), root length (RL), root volume (RV), root diameter (RD) <1 mm and 1 <(RD) <2 mm were the most important growth parameters in the separation of T. cacao genotypes in to tolerant and intolerant to soil water deficit.

Venous Thromboembolism and Cerebrovascular Events in Patients with Giant Cell Arteritis: A Population-Based Retrospective Cohort Study

PubMed Central

Crowson, Cynthia S.; Makol, Ashima; Ytterberg, Steven R.; Saitta, Antonino; Salvarani, Carlo; Matteson, Eric L.; Warrington, Kenneth J.

2016-01-01

Objective To investigate the incidence of venous thromboembolism (VTE) and cerebrovascular events in a community-based incidence cohort of patients with giant cell arteritis (GCA) compared to the general population. Methods A population-based inception cohort of patients with incident GCA between January 1, 1950 and December 31, 2009 in Olmsted County, Minnesota and a cohort of non-GCA subjects from the same population were assembled and followed until December 31, 2013. Confirmed VTE and cerebrovascular events were identified through direct medical record review. Results The study population included 244 patients with GCA with a mean ± SD age at diagnosis of 76.2 ± 8.2 years (79% women) and an average length of follow-up of 10.2 ± 6.8 years. Compared to non-GCA subjects of similar age and sex, patients diagnosed with GCA had a higher incidence (%) of amaurosis fugax (cumulative incidence ± SE: 2.1 ± 0.9 versus 0, respectively; p = 0.014) but similar rates of stroke, transient ischemic attack (TIA), and VTE. Among patients with GCA, neither baseline characteristics nor laboratory parameters at diagnosis reliably predicted risk of VTE or cerebrovascular events. Conclusion In this population-based study, the incidence of VTE, stroke and TIA was similar in patients with GCA compared to non-GCA subjects. PMID:26901431

A Low Affinity GCaMP3 Variant (GCaMPer) for Imaging the Endoplasmic Reticulum Calcium Store.

PubMed

Henderson, Mark J; Baldwin, Heather A; Werley, Christopher A; Boccardo, Stefano; Whitaker, Leslie R; Yan, Xiaokang; Holt, Graham T; Schreiter, Eric R; Looger, Loren L; Cohen, Adam E; Kim, Douglas S; Harvey, Brandon K

2015-01-01

Endoplasmic reticulum calcium homeostasis is critical for cellular functions and is disrupted in diverse pathologies including neurodegeneration and cardiovascular disease. Owing to the high concentration of calcium within the ER, studying this subcellular compartment requires tools that are optimized for these conditions. To develop a single-fluorophore genetically encoded calcium indicator for this organelle, we targeted a low affinity variant of GCaMP3 to the ER lumen (GCaMPer (10.19)). A set of viral vectors was constructed to express GCaMPer in human neuroblastoma cells, rat primary cortical neurons, and human induced pluripotent stem cell-derived cardiomyocytes. We observed dynamic changes in GCaMPer (10.19) fluorescence in response to pharmacologic manipulations of the ER calcium store. Additionally, periodic calcium efflux from the ER was observed during spontaneous beating of cardiomyocytes. GCaMPer (10.19) has utility in imaging ER calcium in living cells and providing insight into luminal calcium dynamics under physiologic and pathologic states.

UCH-LI acts as a novel prognostic biomarker in gastric cardiac adenocarcinoma.

PubMed

Yang, Honghong; Zhang, Chunhong; Fang, Shan; Ou, Rongying; Li, Wenfeng; Xu, Yunsheng

2015-01-01

Gastric cardiac adenocarcinoma (GCA) accounts for a majority of gastric cancer population and harbors unfavorable outcome. Ubiquitin C-terminal hydrolase L1 (UCH-L1) belongs to the deubiquitinating enzyme family, which could regulate cell growth in human cancers. In the present study, expression of UCH-L1 was evaluated in 196 GCAs by immunohistochemistry using tissue microarray and its function on gastric cancer cells was measured. UCH-L1 expression was increased in GCA specimens, compared with their normal tissues and UCH-L1 overexpression is tightly correlated with tumor size and overall TNM stage. Log-rank analysis showed that UCH-L1 positive is reversely associated with cumulative survival (P<0.001). Multivariate Cox regression model showed that UCH-L1 overexpression is a remarkably negative predictor in GCA prognosis (Hazard Ratio=0.53, P<0.01), along with advanced TNM stage that is a known negative factor in gastric cancers (Hazard Ratio=0.33, P<0.05). Silencing of UCH-L1 reduced the ability of cell proliferation, colony formation, migration and invasion of gastric cancer cells. Our findings suggest that UCH-L1 is a promising prognostic biomarker for GCAs and might play an important role in the carcinogenesis of gastric cancer.

Simultaneous Presentation of Giant Cell Arteritis and Myelodysplastic Syndrome in an Elderly Japanese Man.

PubMed

Senjo, Hajime; Higuchi, Takakazu; Morimoto, Masaya; Koyamada, Ryosuke; Yanaoka, Chisun; Okada, Sadamu

2018-05-18

An 81-year-old Japanese man presented with constitutional symptoms and anemia and was diagnosed with giant cell arteritis (GCA) and myelodysplastic syndrome (MDS) simultaneously. His symptoms and anemia improved promptly with steroids; however, the MDS rapidly progressed to overt leukemia. While MDS patients are at an increased risk of autoimmune diseases, an association with GCA has rarely been reported. This case illustrates the importance of considering GCA as a cause of anemia in elderly patients if MDS is already diagnosed, even in countries where the prevalence of GCA is very low. The simultaneous development of GCA and MDS suggests a common pathogenetic link between these two diseases.

Total internal reflectance fluorescence imaging of genetically engineered ryanodine receptor-targeted Ca2+ probes in rat ventricular myocytes.

PubMed

Pahlavan, Sara; Morad, Marin

2017-09-01

The details of cardiac Ca 2+ signaling within the dyadic junction remain unclear because of limitations in rapid spatial imaging techniques, and availability of Ca 2+ probes localized to dyadic junctions. To critically monitor ryanodine receptors' (RyR2) Ca 2+ nano-domains, we combined the use of genetically engineered RyR2-targeted pericam probes, (FKBP-YCaMP, K d =150nM, or FKBP-GCaMP6, K d =240nM) with rapid total internal reflectance fluorescence (TIRF) microscopy (resolution, ∼80nm). The punctate z-line patterns of FKBP, 2 -targeted probes overlapped those of RyR2 antibodies and sharply contrasted to the images of probes targeted to sarcoplasmic reticulum (SERCA2a/PLB), or cytosolic Fluo-4 images. FKBP-YCaMP signals were too small (∼20%) and too slow (2-3s) to detect Ca 2+ sparks, but the probe was effective in marking where Fluo-4 Ca 2+ sparks developed. FKBP-GCaMP6, on the other hand, produced rapidly decaying Ca 2+ signals that: a) had faster kinetics and activated synchronous with I Ca 3 but were of variable size at different z-lines and b) were accompanied by spatially confined spontaneous Ca 2+ sparks, originating from a subset of eager sites. The frequency of spontaneously occurring sparks was lower in FKBP-GCaMP6 infected myocytes as compared to Fluo-4 dialyzed myocytes, but isoproterenol enhanced their frequency more effectively than in Fluo-4 dialyzed cells. Nevertheless, isoproterenol failed to dissociate FKBP-GCaMP6 from the z-lines. The data suggests that FKBP-GCaMP6 binds predominantly to junctional RyR2s and has sufficient on-rate efficiency as to monitor the released Ca 2+ in individual dyadic clefts, and supports the idea that β-adrenergic agonists may modulate the stabilizing effects of native FKBP on RyR2. Copyright © 2017 Elsevier Ltd. All rights reserved.

Which Patients with Giant Cell Arteritis Will Develop Cardiovascular or Cerebrovascular Disease? A Clinical Practice Research Datalink Study.

PubMed

Robson, Joanna C; Kiran, Amit; Maskell, Joe; Hutchings, Andrew; Arden, Nigel; Dasgupta, Bhaskar; Hamilton, William; Emin, Akan; Culliford, David; Luqmani, Raashid

2016-06-01

To evaluate the risk of cerebrovascular disease and cardiovascular disease (CVD) in patients with giant cell arteritis (GCA), and to identify predictors. The UK Clinical Practice Research Datalink 1991-2010 was used for a parallel cohort study of 5827 patients with GCA and 37,090 age-, sex-, and location-matched controls. A multivariable competing risk model (non-cerebrovascular/CV-related death as the competing risk) determined the relative risk [subhazard ratio (SHR)] between patients with GCA compared with background controls for cerebrovascular disease, CVD, or either. Each cohort (GCA and controls) was then analyzed individually using the same multivariable model, with age and sex now present, to identify predictors of CVD or cerebrovascular disease. Patients with GCA, compared with controls, had an increased risk SHR (95% CI) of cerebrovascular disease (1.45, 1.31-1.60), CVD (1.49, 1.37-1.62), or either (1.47, 1.37-1.57). In the GCA cohort, predictors of "cerebrovascular disease or CVD" included increasing age, > 80 years versus < 65 years (1.98, 1.62-2.42), male sex (1.20, 1.05-1.38), and socioeconomic status, most deprived quintile versus least deprived (1.34, 1.01-1.78). These predictors were also present within the non-GCA cohort. Patients with GCA are more likely to develop cerebrovascular disease or CVD than age-, sex-, and location-matched controls. In common with the non-GCA cohort, patients who are older, male, and from the most deprived compared with least deprived areas have a higher risk of cerebrovascular disease or CVD. Further work is needed to understand how this risk may be mediated by specific behavioral, social, and economic factors.

Associations Between Prediagnostic Concentrations of Circulating Sex Steroid Hormones and Esophageal/Gastric Cardia Adenocarcinoma Among Men.

PubMed

Petrick, Jessica L; Hyland, Paula L; Caron, Patrick; Falk, Roni T; Pfeiffer, Ruth M; Dawsey, Sanford M; Abnet, Christian C; Taylor, Philip R; Weinstein, Stephanie J; Albanes, Demetrius; Freedman, Neal D; Gapstur, Susan M; Bradwin, Gary; Guillemette, Chantal; Campbell, Peter T; Cook, Michael B

2018-05-17

Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are characterized by a strong male predominance. Concentrations of sex steroid hormones have been hypothesized to explain this sex disparity. However, no prospective population-based study has examined sex steroid hormones in relation to EA/GCA risk. Thus, we investigated whether prediagnostic circulating sex steroid hormone concentrations were associated with EA/GCA in a nested case-control study drawn from participants in three prospective cohort studies. Using gas chromatography-mass spectrometry (GC-MS) and electrochemiluminescence immunoassay, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in serum from 259 EA/GCA male case participants and 259 matched male control participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and Cancer Prevention Study II Nutrition Cohort. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA/GCA risk. All statistical tests were two-sided. Higher concentrations of dehydroepiandrosterone (DHEA) were associated with a 38% decreased risk of EA/GCA (OR per unit increase in log2 DHEA = 0.62, 95% CI = 0.47 to 0.82, Ptrend = .001). Higher estradiol concentrations were associated with a 34% reduced risk of EA/GCA (OR = 0.66, 95% CI = 0.45 to 0.98, Ptrend = .05), and the association with free estradiol was similar. No other associations between baseline hormone concentrations and future EA/GCA risk were observed. This study provides the first evidence that higher concentrations of circulating DHEA, estradiol, and free estradiol may be associated with lower risks of EA/GCA in men.

[Analysis of pesticides including chlorine in welsh onions and mushrooms using gas chromatograph with an atomic emission detector (GC-AED)].

PubMed

Tateishi, Yukinari; Takano, Ichiro; Kobayashi, Maki; Tamura, Yasuhiro; Tomizawa, Sanae; Sakai, Naoko; Kamijo, Kyoko; Nagayama, Toshihiro; Kamata, Kunihiro

2004-12-01

An analytical method for the determination of 32 kinds of pesticide residues in onions, Welsh onions and mushrooms using gas chromatograph with an atomic emission detector (GC-AED) was developed. The pesticides were extracted with acetone-n-hexane (2:3) mixture. The crude extract was partitioned between 5% sodium chloride and ethyl acetate-n-hexane (1:4) mixture. The extract was passed through a Florisil mini-column for cleanup with 10 mL of acetone-n-hexane (1:9) mixture. Although the sensitivity of GC-AED was inferior to that of GC-ECD, GC-AED has a superior element-selectivity. Therefore pesticide residues in foods could be analyzed more exactly by using GC-AED. Thirty-two pesticides including chlorine in onion, Welsh onion and shiitake mushroom were detected without interference. Recoveries of these pesticides from samples determined by GC-AED were 64-114%, except for a few pesticides.

Biological treatments in giant cell arteritis & Takayasu arteritis.

PubMed

Samson, Maxime; Espígol-Frigolé, Georgina; Terrades-García, Nekane; Prieto-González, Sergio; Corbera-Bellalta, Marc; Alba-Rovira, Roser; Hernández-Rodríguez, José; Audia, Sylvain; Bonnotte, Bernard; Cid, Maria C

2018-04-01

Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are the two main large vessel vasculitides. They share some similarities regarding their clinical, radiological and histological presentations but some pathogenic processes in GCA and TAK are activated differently, thus explaining their different sensitivity to biological therapies. The treatment of GCA and TAK essentially relies on glucocorticoids. However, thanks to major progress in our understanding of their pathogenesis, the role of biological therapies in the treatment of these two vasculitides is expanding, especially in relapsing or refractory diseases. In this review, the efficacy, the safety and the limits of the main biological therapies ever tested in GCA and TAK are discussed. Briefly, anti TNF-α agents appear to be effective in treating TAK but not GCA. Recent randomized placebo-controlled trials have reported on the efficacy and safety of abatacept and mostly tocilizumab in inducing and maintaining remission of GCA. Abatacept was not effective in TAK and robust data are still lacking to draw any conclusions concerning the use of tocilizumab in TAK. Furthermore, ustekinumab appears promising in relapsing/refractory GCA whereas rituximab has been reported to be effective in only a few cases of refractory TAK patients. If a biological therapy is indicated, and in light of the data discussed in this review, the first choice would be tocilizumab in GCA and anti-TNF-α agents (mainly infliximab) in TAK. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Environmental risk factors in the development of adenocarcinoma of the oesophagus or gastric cardia: a cross-sectional study in a Dutch cohort.

PubMed

DE Jonge, P J F; Wolters, L M M; Steyerberg, E W; VAN Dekken, H; Kusters, J G; Kuipers, E J; Siersema, P D

2007-07-01

Risk factors for adenocarcinoma of the oesophagus (OAC) and gastric cardia (GCA) are not yet established. To compare environmental risk factors between patients with OAC and GCA. One-hundred and twenty-six patients with OAC, 43 with GCA and 57 with squamous cell carcinoma filled out a questionnaire with information on demographic and lifestyle characteristics, physical activity levels, family history, gastro-oesophageal reflux disease symptoms and medication use. OAC and GCA patients were similar with regard to male predominance and age, alcohol intake and smoking, use of fruits and vegetables, body posture and occupational activities (P > 0.05). GCA patients less often had heartburn compared with OAC patients [odds ratio (OR) 0.5, 95% confidence interval (CI) 0.2-0.96] and had these symptoms less frequently and for a shorter period (OR 0.3, CI 0.1-1.0 and OR 0.1, CI 0.03-0.6, respectively). Former and current aspirin use was lower among GCA patients than OAC patients (OR 0.2, CI 0.05-0.7 and OR 0.4, CI 0.1-0.9, respectively), whereas no difference in non-steroidal anti-inflammatory drug use was detected. Although OAC and GCA share several environmental risk factors, OAC is more frequently associated with a history of gastro-oesophageal reflux disease, suggesting a more important role for gastro-oesophageal reflux in OAC compared with GCA.

[Correlations between serine hydroxymethyltransferase1 C1420T polymorphisms and susceptibilities to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma].

PubMed

Wang, Yi-Min; Guo, Wei; Zhang, Xiu-Feng; Li, Yan; Wang, Na; Ge, Hui; Wei, Li-Zhen; Wen, Deng-Gui; Zhang, Jian-Hui

2006-03-01

Serine hydroxymethyltransferase (SHMT), a key enzyme in the folate metabolism, affects gene methylation and DNA synthesis through providing one-carbon units for purine, thymidylate, and methionine. It is closely related to the development and progression of tumors. This study was to investigate the correlations between SHMT1 C1420T single nucleotide polymorphisms (SNP) and susceptibilities to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA). SHMT1 C1420T SNP was genotyped by polymerase chain reaction-confronting two-pair primers (PCR-CTPP) analysis in 584 ESCC patients, 467 GCA patients, and 540 healthy controls. The correlations between SHMT1 C1420T SNP polymorphisms and susceptibilities to ESCC and GCA were analyzed with Logistic regression model. Family history of upper gastrointestinal cancer (UGIC) significantly enhanced the risk of developing ESCC and GCA [the age, gender, smoking status, and family history of UGIC adjusted odds ratio (OR)=2.89, 95% confident interval (CI)=2.23-3.73; OR =1.68, 95% CI=1.28-2.23]. The frequency of 1420C/T genotype was significantly lower in ESCC and GCA patients than in healthy controls (12.0% vs. 16.5%, P<0.05; 10.9% vs. 16.5%, P<0.01). Compared with C/C genotype, C/T genotype significantly reduced susceptibilities to ESCC and GCA, with adjusted OR of 0.70 (95% CI=0.50-0.98) for ESCC and 0.55 (95% CI=0.38-0.81) for GCA. Stratification analysis showed that C/T genotype significantly reduced susceptibilities to ESCC and GCA among non-smokers, with adjusted OR of 0.54 (95% CI=0.33-0.90) for ESCC and 0.56 (95% CI=0.33-0.95) for GCA. In addition, C/T genotype significantly reduced susceptibility to GCA among individuals with or without UGIC history, with adjusted OR of 0.46 (95%CI=0.24-0.90) and 0.62 (95% CI=0.38-0.99) respectively, and reduced susceptibility to ESCC only among individuals with UGIC history, with adjusted OR of 0.51 (95% CI=0.29-0.89). SHMT1 1420C/T genotype could significantly reduce susceptibilities to ESCC and GCA among individuals from high risk areas in Hebei Province of China.

76 FR 65212 - Caterpillar, Inc., Large Power Systems Division, Including On-Site Leased Workers From Gray...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-20

..., River City, GCA, Lozier, Obrien Bros., HK, FCA and Clifton Gunderson, Mossville, IL; Amended..., Inc., ATS, URS, River City, GCA, Lozier, Obrien Bros., HK, FCA, and Clifton Gunderson were employed on... Interplant Systems, Inc., ATS, URS, River City, GCA, Lozier, Obrien Bros., HK, FCA, and Clifton Gunderson...

Do solar cycles influence giant cell arteritis and rheumatoid arthritis incidence?

DOE PAGES

Wing, Simon; Rider, Lisa G.; Johnson, Jay R.; ...

2015-05-15

Our objective was to examine the influence of solar cycle and geomagnetic effects on the incidence of giant cell arteritis (GCA) and rheumatoid arthritis (RA). Methods: We used data from patients with GCA (1950-2004) and RA (1955-2007) obtained from population-based cohorts. Yearly trends in age-adjusted and sex-adjusted incidence were correlated with the F10.7 index (solar radiation at 10.7 cm wavelength, a proxy for the solar extreme ultraviolet radiation) and AL index (a proxy for the westward auroral electrojet and a measure of geomagnetic activity). Fourier analysis was performed on AL, F10.7, and GCA and RA incidence rates. Results: The correlationmore » of GCA incidence with AL is highly significant: GCA incidence peaks 0-1 year after the AL reaches its minimum (ie, auroral electrojet reaches a maximum). The correlation of RA incidence with AL is also highly significant. RA incidence rates are lowest 5-7 years after AL reaches maximum. AL, GCA and RA incidence power spectra are similar: they have a main peak (periodicity) at about 10 years and a minor peak at 4-5 years. However, the RA incidence power spectrum main peak is broader (8-11 years), which partly explains the lower correlation between RA onset and AL. The auroral electrojets may be linked to the decline of RA incidence more strongly than the onset of RA. The incidences of RA and GCA are aligned in geomagnetic latitude. Conclusions: AL and the incidences of GCA and RA all have a major periodicity of about 10 years and a secondary periodicity at 4-5 years. Geomagnetic activity may explain the temporal and spatial variations, including east-west skewness in geographic coordinates, in GCA and RA incidence, although the mechanism is unknown. Lastly, the link with solar, geospace and atmospheric parameters need to be investigated. These novel findings warrant examination in other populations and with other autoimmune diseases.« less

The relative risk of aortic aneurysm in patients with giant cell arteritis compared with the general population of the UK.

PubMed

Robson, Joanna C; Kiran, Amit; Maskell, Joe; Hutchings, Andrew; Arden, Nigel; Dasgupta, Bhaskar; Hamilton, William; Emin, Akan; Culliford, David; Luqmani, Raashid A

2015-01-01

To evaluate the risk of aortic aneurysm in patients with giant cell arteritis (GCA) compared with age-, gender- and location-matched controls. A UK General Practice Research Database (GPRD) parallel cohort study of 6999 patients with GCA and 41 994 controls, matched on location, age and gender, was carried out. A competing risk model using aortic aneurysm as the primary outcome and non-aortic-aneurysm-related death as the competing risk was used to determine the relative risk (subhazard ratio) between non-GCA and GCA subjects, after adjustment for cardiovascular risk factors. Comparing the GCA cohort with the non-GCA cohort, the adjusted subhazard ratio (95% CI) for aortic aneurysm was 1.92 (1.52 to 2.41). Significant predictors of aortic aneurysm were being an ex-smoker (2.64 (2.03 to 3.43)) or a current smoker (3.37 (2.61 to 4.37)), previously taking antihypertensive drugs (1.57 (1.23 to 2.01)) and a history of diabetes (0.32 (0.19 to 0.56)) or cardiovascular disease (1.98 (1.50 to 2.63)). In a multivariate model of the GCA cohort, male gender (2.10 (1.38 to 3.19)), ex-smoker (2.20 (1.22 to 3.98)), current smoker (3.79 (2.20 to 6.53)), previous antihypertensive drugs (1.62 (1.00 to 2.61)) and diabetes (0.19 (0.05 to 0.77)) were significant predictors of aortic aneurysm. Patients with GCA have a twofold increased risk of aortic aneurysm, and this should be considered within the range of other risk factors including male gender, age and smoking. A separate screening programme is not indicated. The protective effect of diabetes in the development of aortic aneurysms in patients with GCA is also demonstrated. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Do solar cycles influence giant cell arteritis and rheumatoid arthritis incidence?

PubMed Central

Wing, Simon; Rider, Lisa G; Johnson, Jay R; Miller, Federick W; Matteson, Eric L; Gabriel, Sherine E

2015-01-01

Objective To examine the influence of solar cycle and geomagnetic effects on the incidence of giant cell arteritis (GCA) and rheumatoid arthritis (RA). Methods We used data from patients with GCA (1950–2004) and RA (1955–2007) obtained from population-based cohorts. Yearly trends in age-adjusted and sex-adjusted incidence were correlated with the F10.7 index (solar radiation at 10.7 cm wavelength, a proxy for the solar extreme ultraviolet radiation) and AL index (a proxy for the westward auroral electrojet and a measure of geomagnetic activity). Fourier analysis was performed on AL, F10.7, and GCA and RA incidence rates. Results The correlation of GCA incidence with AL is highly significant: GCA incidence peaks 0–1 year after the AL reaches its minimum (ie, auroral electrojet reaches a maximum). The correlation of RA incidence with AL is also highly significant. RA incidence rates are lowest 5–7 years after AL reaches maximum. AL, GCA and RA incidence power spectra are similar: they have a main peak (periodicity) at about 10 years and a minor peak at 4–5 years. However, the RA incidence power spectrum main peak is broader (8–11 years), which partly explains the lower correlation between RA onset and AL. The auroral electrojets may be linked to the decline of RA incidence more strongly than the onset of RA. The incidences of RA and GCA are aligned in geomagnetic latitude. Conclusions AL and the incidences of GCA and RA all have a major periodicity of about 10 years and a secondary periodicity at 4–5 years. Geomagnetic activity may explain the temporal and spatial variations, including east-west skewness in geographic coordinates, in GCA and RA incidence, although the mechanism is unknown. The link with solar, geospace and atmospheric parameters need to be investigated. These novel findings warrant examination in other populations and with other autoimmune diseases. PMID:25979866

Do solar cycles influence giant cell arteritis and rheumatoid arthritis incidence?

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

Wing, Simon; Rider, Lisa G.; Johnson, Jay R.

Our objective was to examine the influence of solar cycle and geomagnetic effects on the incidence of giant cell arteritis (GCA) and rheumatoid arthritis (RA). Methods: We used data from patients with GCA (1950-2004) and RA (1955-2007) obtained from population-based cohorts. Yearly trends in age-adjusted and sex-adjusted incidence were correlated with the F10.7 index (solar radiation at 10.7 cm wavelength, a proxy for the solar extreme ultraviolet radiation) and AL index (a proxy for the westward auroral electrojet and a measure of geomagnetic activity). Fourier analysis was performed on AL, F10.7, and GCA and RA incidence rates. Results: The correlationmore » of GCA incidence with AL is highly significant: GCA incidence peaks 0-1 year after the AL reaches its minimum (ie, auroral electrojet reaches a maximum). The correlation of RA incidence with AL is also highly significant. RA incidence rates are lowest 5-7 years after AL reaches maximum. AL, GCA and RA incidence power spectra are similar: they have a main peak (periodicity) at about 10 years and a minor peak at 4-5 years. However, the RA incidence power spectrum main peak is broader (8-11 years), which partly explains the lower correlation between RA onset and AL. The auroral electrojets may be linked to the decline of RA incidence more strongly than the onset of RA. The incidences of RA and GCA are aligned in geomagnetic latitude. Conclusions: AL and the incidences of GCA and RA all have a major periodicity of about 10 years and a secondary periodicity at 4-5 years. Geomagnetic activity may explain the temporal and spatial variations, including east-west skewness in geographic coordinates, in GCA and RA incidence, although the mechanism is unknown. Lastly, the link with solar, geospace and atmospheric parameters need to be investigated. These novel findings warrant examination in other populations and with other autoimmune diseases.« less

Ethnicity and H. pylori as risk factors for gastric cancer in Malaysia: A prospective case control study.

PubMed

Goh, Khean-Lee; Cheah, Phaik-Leng; Md, Noorfaridah; Quek, Kia-Fatt; Parasakthi, Navaratnam

2007-01-01

To determine the risk factors for gastric cancer (GCA), with particular emphasis on ethnicity in our multiracial population. A prospective case control study with ratio of cancer:controls of 1:2. Diagnosis of H. pylori was made by serology using the ELISA technique. Dietary intake was assessed by dietary recall over the preceding 6 months. Eighty-seven cases of GCA were enrolled. The cancers were predominantly distal in location and of the intestinal type. Risk factors identified following multiple logistic regression analysis were: Chinese race (OR 10.23 [2.87-36.47]), H. pylori (OR 2.54 [1.16-5.58]), low level of education (OR 9.81 [2.03-47.46]), smoking (OR 2.52 [1.23-5.15]), and high intake of salted fish and vegetables (OR 5.18 [1.35-20.00]) were identified as significant independent risk factors for GCA, while high intake of fresh fruits and vegetables was protective for GCA (OR 0.15 [0.04-0.64]). Chili intake was not a significant protective factor following multivariate analysis. Chinese race was a strong independent predictor of GCA. H. pylori was an important predictor of GCA with a 2.5-fold greater risk in our patients. Despite a high prevalence of H. pylori, the prevalence of GCA among Indians was low and this paradox can be appropriately called the "Indian enigma."

A new chicken genome assembly provides insight into avian genome structure

USDA-ARS?s Scientific Manuscript database

The importance of the Gallus gallus (chicken) as a model organism and agricultural animal merits a continuation of sequence assembly improvement efforts. We present a new version of the chicken genome assembly (Gallus_gallus-5.0; GCA_000002315.3) built from combined long single molecule sequencing t...

Comparison of idiopathic (isolated) aortitis and giant cell arteritis-related aortitis. A French retrospective multicenter study of 117 patients.

PubMed

Espitia, Olivier; Samson, Maxime; Le Gallou, Thomas; Connault, Jérôme; Landron, Cedric; Lavigne, Christian; Belizna, Cristina; Magnant, Julie; de Moreuil, Claire; Roblot, Pascal; Maillot, François; Diot, Elisabeth; Jégo, Patrick; Durant, Cécile; Masseau, A; Brisseau, Jean-Marie; Pottier, Pierre; Espitia-Thibault, Alexandra; Santos, Anabele Dos; Perrin, François; Artifoni, Mathieu; Néel, Antoine; Graveleau, Julie; Moreau, Philippe; Maisonneuve, Hervé; Fau, Georges; Serfaty, Jean-Michel; Hamidou, Mohamed; Agard, Christian

2016-06-01

The aim of the study was to compare clinical/imaging findings and outcome in patients with idiopathic (isolated aortitis, IA) and with giant cell arteritis (GCA)-related aortitis. Patients from 11 French internal medicine departments were retrospectively included. Aortitis was defined by aortic wall thickening >2mm and/or an aortic aneurysm on CT-scan, associated to inflammatory syndrome. Patients with GCA had at least 3 ACR criteria. Aortic events (aneurysm, dissection, aortic surgeries) were reported, and free of aortic events-survival were compared. Among 191 patients with non-infectious aortitis, 73 with GCA and 44 with IA were included. Patients with IA were younger (65 vs 70 years, p=0.003) and comprised more past/current smokers (43 vs 15%, p=0.0007). Aortic aneurisms were more frequent (38% vs 20%, p=0.03), and aortic wall thickening was more pronounced in IA. During follow-up (median=34 months), subsequent development of aortic aneurysm was significantly lower in GCA when compared to IA (p=0.009). GCA patients required significantly less aortic surgery during follow-up than IA patients (p=0.02). Mean age, sex ratio, inflammatory parameters, and free of aortic aneurism survival were equivalent in patients with IA ≥ 60 years when compared to patients with GCA-related aortitis. IA is more severe than aortitis related to GCA, with higher proportions of aortic aneurism at diagnosis and during follow-up. IA is a heterogeneous disease and its prognosis is worse in younger patients <60 years. Most patients with IA ≥ 60 years share many features with GCA-related aortitis. Copyright © 2016 Elsevier B.V. All rights reserved.

The Leganés cognitive test correlates poorly with MRI evidence of global cortical atrophy in an underserved community: A population-based and nested case-control study in rural Ecuador (The Atahualpa Project)

PubMed Central

Brutto, Oscar H. Del; Mera, Robertino M; Zambrano, Mauricio; Lama, Julio

2014-01-01

Objective We aimed to evaluate whether the Leganés cognitive test (LCT) correlates with global cortical atrophy (GCA) and can be used as a surrogate for structural brain damage. Methods Atahualpa residents aged > 60 years identified during a door-to-door survey underwent MRI for grading GCA. Using multivariate generalized linear models, we evaluated whether continuous LCT scores correlated with GCA, after adjusting for demographics, education, cardiovascular health (CVH) status, depression and edentulism. In a nested case-control study, GCA severity was assessed in subjects with LCT scores below the cutoff level for dementia (< 22 points) and in matched controls without dementia. Results Out of 311 eligible subjects, 241 (78%) were enrolled. Mean age was 69.2±7.5 years, 59% were women, 83% had primary school education, 73% had poor CVH status, 12% had symptoms of depression and 43% had edentulism. Average LCT score was 26.7±3, and 23 (9.5%) subjects scored < 22 points. GCA was mild in 108, moderate in 95, and severe in 26 individuals. On the multivariate model, mean LCT score was not associated with GCA severity (β=0.06, SE=0.34, p=0.853). Severe GCA was noted in 6 / 23 case-patients and in 8 / 23 controls (OR: 0.67, 95% CI: 0.14-2.81, p=0.752, McNemar's test). Conclusion The LCT does not correlate with severity of GCA after adjusting for potential confounding variables, and should not be used as a reliable estimate of structural brain damage. PMID:29213925

The Leganés cognitive test correlates poorly with MRI evidence of global cortical atrophy in an underserved community: A population-based and nested case-control study in rural Ecuador (The Atahualpa Project).

PubMed

Brutto, Oscar H Del; Mera, Robertino M; Zambrano, Mauricio; Lama, Julio

2014-01-01

We aimed to evaluate whether the Leganés cognitive test (LCT) correlates with global cortical atrophy (GCA) and can be used as a surrogate for structural brain damage. Atahualpa residents aged > 60 years identified during a door-to-door survey underwent MRI for grading GCA. Using multivariate generalized linear models, we evaluated whether continuous LCT scores correlated with GCA, after adjusting for demographics, education, cardiovascular health (CVH) status, depression and edentulism. In a nested case-control study, GCA severity was assessed in subjects with LCT scores below the cutoff level for dementia (< 22 points) and in matched controls without dementia. Out of 311 eligible subjects, 241 (78%) were enrolled. Mean age was 69.2±7.5 years, 59% were women, 83% had primary school education, 73% had poor CVH status, 12% had symptoms of depression and 43% had edentulism. Average LCT score was 26.7±3, and 23 (9.5%) subjects scored < 22 points. GCA was mild in 108, moderate in 95, and severe in 26 individuals. On the multivariate model, mean LCT score was not associated with GCA severity (β=0.06, SE=0.34, p=0.853). Severe GCA was noted in 6 / 23 case-patients and in 8 / 23 controls (OR: 0.67, 95% CI: 0.14-2.81, p=0.752, McNemar's test). The LCT does not correlate with severity of GCA after adjusting for potential confounding variables, and should not be used as a reliable estimate of structural brain damage.

Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation

PubMed Central

Liu, Shin-Yun; Shun, Chia-Tung; Hung, Kuan-Yu; Juan, Hsueh-Fen; Hsu, Chia-Lang; Huang, Min-Chuan; Lai, I-Rue

2016-01-01

Glycosylation affects malignancy in cancer. Here, we report that N- acetylgalactosaminyltransferase 2 (GALNT2), an enzyme that mediates the initial step of mucin type-O glycosylation, suppresses malignant phenotypes in gastric adenocarcinoma (GCA) by modifying MET (Hepatocyte growth factor receptor) activity. GALNT2 mRNA and protein were downregulated in GCAs, and this reduction was associated with more advanced disease stage and shorter recurrence-free survival. Suppressing GALNT2 expression in GCA cells increased cell growth, migration, and invasion in vitro, and tumor metastasis in vivo. GALNT2 knockdown enhanced phosphorylation of MET and decreased expression of the Tn antigen on MET. Inhibiting MET activity with PHA665752 decreased the malignant phenotypes caused by GALNT2 knockdown in GCA cells. Our results indicate that GALNT2 suppresses the malignant potential of GCA cells and provide novel insights into the significance of O-glycosylation in MET activity and GCA progression. PMID:26848976

In vivo optoacoustic monitoring of calcium activity in the brain (Conference Presentation)

NASA Astrophysics Data System (ADS)

Deán-Ben, Xose Luís.; Gottschalk, Sven; Sela, Gali; Lauri, Antonella; Kneipp, Moritz; Ntziachristos, Vasilis; Westmeyer, Gil G.; Shoham, Shy; Razansky, Daniel

2017-03-01

Non-invasive observation of spatio-temporal neural activity of large neural populations distributed over the entire brain of complex organisms is a longstanding goal of neuroscience [1,2]. Recently, genetically encoded calcium indicators (GECIs) have revolutionized neuroimaging by enabling mapping the activity of entire neuronal populations in vivo [3]. Visualization of these powerful sensors with fluorescence microscopy has however been limited to superficial regions while deep brain areas have so far remained unreachable [4]. We have developed a volumetric multispectral optoacoustic tomography platform for imaging neural activation deep in scattering brains [5]. The developed methodology can render 100 volumetric frames per second across scalable fields of view ranging between 50-1000 mm3 with respective spatial resolution of 35-150µm. Experiments performed in immobilized and freely swimming larvae and in adult zebrafish brains expressing the genetically-encoded calcium indicator GCaMP5G demonstrated, for the first time, the fundamental ability to directly track neural dynamics using optoacoustics while overcoming the depth barrier of optical imaging in scattering brains [6]. It was further possible to monitor calcium transients in a scattering brain of a living adult transgenic zebrafish expressing GCaMP5G calcium indicator [7]. Fast changes in optoacoustic traces associated to GCaMP5G activity were detectable in the presence of other strongly absorbing endogenous chromophores, such as hemoglobin. The results indicate that the optoacoustic signal traces generally follow the GCaMP5G fluorescence dynamics and further enable overcoming the longstanding optical-diffusion penetration barrier associated to scattering in biological tissues [6]. The new functional optoacoustic neuroimaging method can visualize neural activity at penetration depths and spatio-temporal resolution scales not covered with the existing neuroimaging techniques. Thus, in addition to the well-established capacity of optoacoustics to resolve vascular anatomy and multiple hemodynamic parameters deep in scattering tissues, the newly developed methodology offers unprecedented capabilities for functional whole brain observations of fast calcium dynamics.

Physico-functional and mechanical properties of chitosan and calcium salts incorporated fish gelatin scaffolds.

PubMed

Jeevithan, E; Jeya Shakila, R; Varatharajakumar, A; Jeyasekaran, G; Sukumar, D

2013-09-01

Four types of fish gelatin scaffolds viz. gelatin (G), gelatin-chitosan (GC), gelatin-calcium acetate (GCA) and gelatin-chitosan-calcium acetate (GCCA) prepared were investigated for their functional properties, biomechanical strength, microstructural changes in relation to biodegradation. GC scaffold was superior with pH 3.15 and viscosity 9.40 cP. Chitosan and calcium acetate improved tensile strength (TS) and Young's modulus (YM), but lowered elongation at break (EAB). GCCA scaffold possessed moderate TS of 19.6 MPa, EAB of 4.76% and YM of 185 MPa. Foaming ability ratio of GC scaffold was high (3.41). GCA and GCCA scaffolds remained for 4 days before complete in vitro biodegradation. GC scaffold had larger cavities (180-300 μm) that were responsible for low swelling ratios and shrinkage factor. GCCA scaffold with moderate swelling rates, mechanical, functional properties and lowered biodegradation rate were found more suitable for biomedical applications. Copyright © 2013 Elsevier B.V. All rights reserved.

6DOF Testing of the SLS Inertial Navigation Unit

NASA Technical Reports Server (NTRS)

Geohagan, Kevin W.; Bernard, William P.; Oliver, T. Emerson; Strickland, Dennis J.; Leggett, Jared O.

2018-01-01

The Navigation System on the NASA Space Launch System (SLS) Block 1 vehicle performs initial alignment of the Inertial Navigation System (INS) navigation frame through gyrocompass alignment (GCA). In lieu of direct testing of GCA accuracy in support of requirement verification, the SLS Navigation Team proposed and conducted an engineering test to, among other things, validate the GCA performance and overall behavior of the SLS INS model through comparison with test data. This paper will detail dynamic hardware testing of the SLS INS, conducted by the SLS Navigation Team at Marshall Space Flight Center's 6DOF Table Facility, in support of GCA performance characterization and INS model validation. A 6-DOF motion platform was used to produce 6DOF pad twist and sway dynamics while a simulated SLS flight computer communicated with the INS. Tests conducted include an evaluation of GCA algorithm robustness to increasingly dynamic pad environments, an examination of GCA algorithm stability and accuracy over long durations, and a long-duration static test to gather enough data for Allan Variance analysis. Test setup, execution, and data analysis will be discussed, including analysis performed in support of SLS INS model validation.

Natriuretic Peptide Receptor Guanylyl Cyclase-A in Podocytes is Renoprotective but Dispensable for Physiologic Renal Function

PubMed Central

Staffel, Janina; Valletta, Daniela; Federlein, Anna; Ehm, Katharina; Volkmann, Regine; Füchsl, Andrea M.; Witzgall, Ralph; Kuhn, Michaela

2017-01-01

The cardiac natriuretic peptides (NPs), atrial NP and B-type NP, regulate fluid homeostasis and arterial BP through renal actions involving increased GFR and vascular and tubular effects. Guanylyl cyclase-A (GC-A), the transmembrane cGMP-producing receptor shared by these peptides, is expressed in different renal cell types, including podocytes, where its function is unclear. To study the effects of NPs on podocytes, we generated mice with a podocyte-specific knockout of GC-A (Podo-GC-A KO). Despite the marked reduction of GC-A mRNA in GC-A KO podocytes to 1% of the control level, Podo-GC-A KO mice and control littermates did not differ in BP, GFR, or natriuresis under baseline conditions. Moreover, infusion of synthetic NPs similarly increased the GFR and renal perfusion in both genotypes. Administration of the mineralocorticoid deoxycorticosterone-acetate (DOCA) in combination with high salt intake induced arterial hypertension of similar magnitude in Podo-GC-A KO mice and controls. However, only Podo-GC-A KO mice developed massive albuminuria (controls: 35-fold; KO: 5400-fold versus baseline), hypoalbuminemia, reduced GFR, and marked glomerular damage. Furthermore, DOCA treatment led to decreased expression of the slit diaphragm-associated proteins podocin, nephrin, and synaptopodin and to enhanced transient receptor potential canonical 6 (TRPC6) channel expression and ATP-induced calcium influx in podocytes of Podo-GC-A KO mice. Concomitant treatment of Podo-GC-A KO mice with the TRPC channel blocker SKF96365 markedly ameliorated albuminuria and glomerular damage in response to DOCA. In conclusion, the physiologic effects of NPs on GFR and natriuresis do not involve podocytes. However, NP/GC-A/cGMP signaling protects podocyte integrity under pathologic conditions, most likely by suppression of TRPC channels. PMID:27153922

Seismic envelope-based detection and location of ground-coupled airwaves from volcanoes in Alaska

USGS Publications Warehouse

Fee, David; Haney, Matt; Matoza, Robin S.; Szuberla, Curt A.L.; Lyons, John; Waythomas, Christopher F.

2016-01-01

Volcanic explosions and other infrasonic sources frequently produce acoustic waves that are recorded by seismometers. Here we explore multiple techniques to detect, locate, and characterize ground‐coupled airwaves (GCA) on volcano seismic networks in Alaska. GCA waveforms are typically incoherent between stations, thus we use envelope‐based techniques in our analyses. For distant sources and planar waves, we use f‐k beamforming to estimate back azimuth and trace velocity parameters. For spherical waves originating within the network, we use two related time difference of arrival (TDOA) methods to detect and localize the source. We investigate a modified envelope function to enhance the signal‐to‐noise ratio and emphasize both high energies and energy contrasts within a spectrogram. We apply these methods to recent eruptions from Cleveland, Veniaminof, and Pavlof Volcanoes, Alaska. Array processing of GCA from Cleveland Volcano on 4 May 2013 produces robust detection and wave characterization. Our modified envelopes substantially improve the short‐term average/long‐term average ratios, enhancing explosion detection. We detect GCA within both the Veniaminof and Pavlof networks from the 2007 and 2013–2014 activity, indicating repeated volcanic explosions. Event clustering and forward modeling suggests that high‐resolution localization is possible for GCA on typical volcano seismic networks. These results indicate that GCA can be used to help detect, locate, characterize, and monitor volcanic eruptions, particularly in difficult‐to‐monitor regions. We have implemented these GCA detection algorithms into our operational volcano‐monitoring algorithms at the Alaska Volcano Observatory.

Topologically massive gravity and galilean conformal algebra: a study of correlation functions

NASA Astrophysics Data System (ADS)

Bagchi, Arjun

2011-02-01

The Galilean Conformal Algebra (GCA) arises from the conformal algebra in the non-relativistic limit. In two dimensions, one can view it as a limit of linear combinations of the two copies Virasoro algebra. Recently, it has been argued that Topologically Massive Gravity (TMG) realizes the quantum 2d GCA in a particular scaling limit of the gravitational Chern-Simons term. To add strength to this claim, we demonstrate a matching of correlation functions on both sides of this correspondence. A priori looking for spatially dependent correlators seems to force us to deal with high spin operators in the bulk. We get around this difficulty by constructing the non-relativistic Energy-Momentum tensor and considering its correlation functions. On the gravity side, our analysis makes heavy use of recent results of Holographic Renormalization in Topologically Massive Gravity.

An immunohistochemical analysis of folate receptor beta expression and distribution in giant cell arteritis - a pilot study

PubMed Central

Albano-Aluquin, Shirley; Malysz, Jozef; Aluquin, Vincent R; Ratnam, Manohar; Olsen, Nancy

2017-01-01

Background: Giant cell arteritis (GCA) is a chronic vasculitis of large and medium vessels in which no targetable biomarkers exist to allow selective treatment, predict disease activity and monitor therapeutic responses. The accessibility of the temporal artery (TA) for biopsy allows morphologic studies to characterize macrophages and T cells in the microenvironment of the arterial wall. We evaluated the expression of folate receptor beta (FRB), a candidate diagnostic/therapeutic biomarker, compared its expression with key macrophage markers and correlated it with GCA severity. Methods: Formalin-fixed paraffin-embedded tissue sections were examined from 6 patients with GCA and 2 controls. Immunohistochemistry was performed using FRB, ETB, CD68 and CD3 antibodies to evaluate for activated macrophages and T cells, assess FRB distribution along the intima, media and adventitial layers and composition of inflammatory infiltrates. We compared the expression of FRB, ETB and CD68 in GCA versus negative controls and in severe (with visual loss) versus mild (without visual loss) disease. Results: In GCA, moderate to severe inflammation was accompanied by >90% destruction of the internal elastic lamina. Macrophages comprised 36.3 ± 4.1% while CD3+ lymphocytes accounted for 61.7 ± 4.1% of total leukocytes. FRB was selectively expressed in macrophages and localized to the adventitia. GCA patients had marginally increased median FRB (9.8 cells/hpf vs. 0; p=0.095), ETB (20.5 vs. 0; p=0.095) and CD68 (38.8 vs. 5; p=0.071) expression versus controls. ETB was found in endothelial cells, smooth muscle cells and macrophages in intima/media. FRB positively correlated with ETB (r=0.90; p-0.037) and CD68 levels (r=0.90; p=0.037). ETB expression positively correlated with CD68 (r=1.0; p<0.0001). There was no difference in FRB between severe and mild GCA. Conclusion: FRB is a potential diagnostic and therapeutic biomarker with restricted expression in GCA macrophages. FRB+ macrophages localized to the adventitia and their expression correlated with ETB and CD68 macrophages, suggesting that they contribute to GCA pathogenesis. PMID:29348986

An Examination of the Demographic and Career Progression of Air Force Institute of Technology Cost Analysis Graduates.

DTIC Science & Technology

1997-09-01

program include the ACEIT software training and the combination of Department of Defense (DOD) application, regression, and statistics. The weaknesses...and Integrated Tools ( ACEIT ) software and training could not be praised enough. AFIT vs. Civilian Institutions. The GCA program provides a Department...very useful to the graduates and beneficial to their careers. The main strengths of the program include the ACEIT software training and the combination

Unusual intraconal localization of orbital giant cell angiofibroma.

PubMed

Ekin, Meryem Altin; Ugurlu, Seyda Karadeniz; Cakalagaoglu, Fulya

2018-01-01

Giant cell angiofibroma (GCA) is a recently reported rare soft-tissue tumor that can develop in various sites including orbit. Orbital GCAs were mainly located in the eyelid or extraconal regions such as lacrimal gland and conjunctiva. We report an atypical case of a GCA arising in the intraconal area of the orbit in a 65-year-old male patient. The tumor was excised in total by lateral orbitotomy. Histological and immunohistochemical features were consistent with the diagnosis of GCA. No recurrence was observed during the follow-up of over 2 years. GCA is a rare tumor that should be considered in the differential diagnosis of intraconal orbital tumors. Complete surgical removal is the current optimal treatment option.

Aortitis in giant cell arteritis: diagnosis with FDG PET/CT and agreement with CT angiography.

PubMed

Hommada, Mona; Mekinian, Arsène; Brillet, Pierre-Yves; Abad, Sébastien; Larroche, Claire; Dhôte, Robin; Fain, Olivier; Soussan, Michael

2017-11-01

To assess the detection rate of aortitis in giant cell arteritis (GCA) with fluorodeoxyglucose positron emission tomography/computed tomography (PET) and to compare the findings with CT angiography (CTA). Fifty-two GCA patients and 27 controls were included. GCA patients had a PET scan at diagnosis (35/52) or during relapse (17/52). Concomitant CTA was performed in 35/52 patients. Aortitis was defined as FDG uptake higher than the liver for PET and wall thickness≥3mm for CTA. Agreement between PET and CTA was evaluated by the kappa coefficient and Spearman correlation coefficient. Aortitis was diagnosed using PET in 40% (14/35) of patients at diagnosis and in 0% of controls (0/27). Agreement was perfect between PET and CT at a patient-based level, and very good at a vascular segment-based level (kappa: 0.72 to 1). PET was positive in 35% (6/17) of patients scanned during GCA relapse, showing aortitis (n=4) and/or articular uptake (n=4). Discrepancies between PET and CT were observed only in relapsing GCA (n=3). Correlation between the maximum standardized uptake value and wall thickness was moderate at diagnosis (r: 0.57 to 0.7) and not statistically significant during relapse. The detection rate of aortitis in GCA patients using PET is 40%, approximately in the range of CTA rates, suggesting that the two techniques have similar sensitivity. PET seems valuable in relapsing GCA, allowing the detection of vascular and articular activities. Copyright © 2017 Elsevier B.V. All rights reserved.

Ustekinumab for refractory giant cell arteritis: A prospective 52-week trial.

PubMed

Conway, Richard; O'Neill, Lorraine; Gallagher, Phil; McCarthy, Geraldine M; Murphy, Conor C; Veale, Douglas J; Fearon, Ursula; Molloy, Eamonn S

2018-04-22

Giant cell arteritis (GCA) is the most common form of systemic vasculitis. Glucocorticoids are an effective treatment but have significant adverse events and relapses are common. Interleukins 12 (IL-12) and 23 (IL-23) stimulate T H 1 and T H 17 responses and are implicated in the pathogenesis of GCA. The aim of this study was to evaluate the efficacy and safety of IL-12/23 blockade with ustekinumab in GCA. We performed a prospective open label study of ustekinumab in patients with refractory GCA. Ustekinumab 90mg was administered subcutaneously every 12 weeks. The primary outcome was the comparison of the median glucocorticoid dose prior to commencement of ustekinumab and at 52 weeks. Secondary outcomes included physician assessed relapse, acute phase reactants, and imaging assessment of large vessel vasculitis (LVV). Twenty-five GCA patients received ustekinumab. All patients had failed to taper glucocorticoids despite addition of a median of 1 other immunosuppressive agent. At week 52, median (IQR) daily prednisolone dose decreased from 20 (15, 25)mg to 5 (2.5, 5)mg (p < 0.001). Six patients (24%) stopped prednisolone completely. No patient experienced a relapse of GCA while receiving ustekinumab. Median (IQR) CRP decreased significantly from 12.9 (5.3, 42) to 6 (2.6, 12.5)mg/L (p = 0.006). CT angiography demonstrated improvement of LVV in all patients studied. No unexpected adverse events were observed with ustekinumab. Ustekinumab may be effective for the treatment of GCA and warrants further assessment in a randomized controlled trial. Copyright © 2018 Elsevier Inc. All rights reserved.

Unusual intraconal localization of orbital giant cell angiofibroma

PubMed Central

Ekin, Meryem Altin; Ugurlu, Seyda Karadeniz; Cakalagaoglu, Fulya

2018-01-01

Giant cell angiofibroma (GCA) is a recently reported rare soft-tissue tumor that can develop in various sites including orbit. Orbital GCAs were mainly located in the eyelid or extraconal regions such as lacrimal gland and conjunctiva. We report an atypical case of a GCA arising in the intraconal area of the orbit in a 65-year-old male patient. The tumor was excised in total by lateral orbitotomy. Histological and immunohistochemical features were consistent with the diagnosis of GCA. No recurrence was observed during the follow-up of over 2 years. GCA is a rare tumor that should be considered in the differential diagnosis of intraconal orbital tumors. Complete surgical removal is the current optimal treatment option. PMID:29283151

Yield performance and stability of CMS-based triticale hybrids.

PubMed

Mühleisen, Jonathan; Piepho, Hans-Peter; Maurer, Hans Peter; Reif, Jochen Christoph

2015-02-01

CMS-based triticale hybrids showed only marginal midparent heterosis for grain yield and lower dynamic yield stability compared to inbred lines. Hybrids of triticale (×Triticosecale Wittmack) are expected to possess outstanding yield performance and increased dynamic yield stability. The objectives of the present study were to (1) examine the optimum choice of the biometrical model to compare yield stability of hybrids versus lines, (2) investigate whether hybrids exhibit a more pronounced grain yield performance and yield stability, and (3) study optimal strategies to predict yield stability of hybrids. Thirteen female and seven male parental lines and their 91 factorial hybrids as well as 30 commercial lines were evaluated for grain yield in up to 20 environments. Hybrids were produced using a cytoplasmic male sterility (CMS)-inducing cytoplasm that originated from Triticumtimopheevii Zhuk. We found that the choice of the biometrical model can cause contrasting results and concluded that a group-by-environment interaction term should be added to the model when estimating stability variance of hybrids and lines. midparent heterosis for grain yield was on average 3 % with a range from -15.0 to 11.5 %. No hybrid outperformed the best inbred line. Hybrids had, on average, lower dynamic yield stability compared to the inbred lines. Grain yield performance of hybrids could be predicted based on midparent values and general combining ability (GCA)-predicted values. In contrast, stability variance of hybrids could be predicted only based on GCA-predicted values. We speculated that negative effects of the used CMS cytoplasm might be the reason for the low performance and yield stability of the hybrids. For this purpose a detailed study on the reasons for the drawback of the currently existing CMS system in triticale is urgently required comprising also the search of potentially alternative hybridization systems.

mTOR pathway is activated in endothelial cells from patients with Takayasu arteritis and is modulated by serum immunoglobulin G.

PubMed

Hadjadj, Jérôme; Canaud, Guillaume; Mirault, Tristan; Samson, Maxime; Bruneval, Patrick; Régent, Alexis; Goulvestre, Claire; Witko-Sarsat, Véronique; Costedoat-Chalumeau, Nathalie; Guillevin, Loïc; Mouthon, Luc; Terrier, Benjamin

2018-06-01

Takayasu arteritis (TA) and GCA are large-vessel vasculitides characterized by vascular remodelling involving endothelial cells (ECs) and vascular smooth muscle cells. Mammalian target of rapamycin (mTOR) pathway has been involved in vascular remodelling. We hypothesized that the mTOR pathway was involved in the pathogenesis of large-vessel vasculitis. We used IF analysis on aortic and temporal artery biopsies from patients with TA and GCA to assess the involvement of the mTOR pathway and searched for antibodies targeting ECs in serum by IIF and cellular ELISA. We evaluated in vitro the effect of purified IgG from patients on mTOR pathway activation and cell proliferation. IF analyses on tissues revealed that both mTORC1 and mTORC2 are activated specifically in ECs from TA patients but not in ECs from GCA patients and healthy controls (HCs). Using IIF and ELISA, we observed higher levels of antibodies binding to ECs in TA patients compared with GCA patients and HCs. Using western blot, we demonstrated that purified IgG from TA patients caused mTORC1 activation in ECs, whereas this effect was not observed with purified IgG from GCA patients or HCs. Purified IgG from TA patients induced a significant EC proliferation compared with to GCA and HC IgG, and this effect was decreased after EC exposure with sirolimus, a specific mTOR inhibitor and PI3K inhibitor. Our results suggest that antibodies targeting ECs drive endothelial remodelling in TA through activation of the mTOR pathway, but not in GCA. Inhibition of the mTOR pathway could represent a therapeutic option in TA.

Isolated aortitis versus giant cell arteritis: are they really two sides of the same coin?

PubMed

Talarico, Rosaria; Boiardi, Luigi; Pipitone, Nicolo'; d'Ascanio, Anna; Stagnaro, Chiara; Ferrari, Claudia; Elefante, Elena; Salvarani, Carlo; Bombardieri, Stefano

2014-01-01

The aim of the study was to compare epidemiological data, clinical findings and results of investigations in patients with isolated aortitis and those with giant cell arteritis (GCA) to establish whether patients with isolated aortitis differ from those with GCA. We reviewed the medical notes of all patients consecutively seen in two Rheumatology centres in the last two decades with a suspicion of GCA, searching for cases characterised by abnormal [18F] fluorodeoxyglucose (FDG) PET uptake of the aorta. 'Isolated aortitis' was defined as increased FDG uptake in the aorta not explained by atherosclerosis in the absence of FDG uptake in other large vessels. Comparing the epidemiological and clinical data of patients with isolated arteritis with those with GCA, we observed many statistical significant differences. First of all, the male/female ratio was reversed, with a predominant male involvement in isolated arteritis. Moreover, the mean age of patients with isolated arteritis was significantly lower than that of GCA patients (62 vs. 78.4 yrs; p<0.0001). None of the patients with isolated aortitis presented at any time of the disease course the typical symptoms of GCA, while in a low percentage of cases constitutional symptoms represented the only clinical features. Beside the aortic arch, the sites more frequent involved were the thoracic and abdominal tracts, in all cases without an uptake of the aortic branches. It is not known whether our patients with isolated aortitis represent variants of GCA or TA, nor is it known how they will evolve, but we can certainly conclude that these patients have a different epidemiologic and clinical profile, and do not necessarily represent two sides of the same coin.

Fever of unknown origin as initial manifestation of large vessel giant cell arteritis: diagnosis by colour-coded sonography and 18-FDG-PET.

PubMed

Czihal, M; Tatò, F; Förster, S; Rademacher, A; Schulze-Koops, H; Hoffmann, U

2010-01-01

To evaluate the clinical characteristics and imaging results (CDS, 18-FDG-PET) of patients with large vessel giant cell arteritis (LV-GCA) presenting as fever of unknown origin (FUO). From a series of 82 patients with GCA we identified 8 patients with FUO as initial disease manifestation. Clinical characteristics and results of CDS and 18-FDG-PET were analysed. Patients with FUO and those with other clinical manifestations of GCA were compared. 18-FDG-PET-scans were available for 6/8 patients, revealing enhanced tracer uptake of the thoracic aorta and the aortic branches in all patients. CDS was performed in 8/8 patients, with detection of hypoechogenic wall thickening related to LV-GCA in 7/8 patients. Subjects with FUO were significantly younger (60.9 vs. 69.3 years, p<0.01) and had a stronger humoral inflammatory response (CRP 12.6 vs. 7.1 mg/dl, p<0.01; ESR 110 vs. 71 mm/hour, p<0.01), when compared to the other GCA-patients. LV-GCA should be considered as important differential diagnosis in patients with FUO. In addition to 18-FDG-PET, which is known to be a valuable method in the diagnostic work-up of FUO, we recommend CDS of the supraaortal and femoropopliteal arteries for the initial diagnostic work-up.

Genetically Encoded Calcium Indicators For Studying Long-Term Calcium Dynamics During Apoptosis

PubMed Central

Garcia, M. Iveth; Chen, Jessica J.; Boehning, Darren

2017-01-01

Intracellular calcium release is essential for regulating almost all cellular functions. Specific spatio-temporal patterns of cytosolic calcium elevations are critical determinants of cell fate in response to pro-apoptotic cellular stressors. As the apoptotic program can take hours or days, measurement of long-term calcium dynamics are essential for understanding the mechanistic role of calcium in apoptotic cell death. Due to the technical limitations of using calcium-sensitive dyes to measure cytosolic calcium little is known about long-term calcium dynamics in living cells after treatment with apoptosis-inducing drugs. Genetically encoded calcium indicators could potentially overcome some of the limitations of calcium-sensitive dyes. Here, we compared the performance of the genetically encoded calcium indicators GCaMP6s and GCaMP6f with the ratiometric dye Fura-2. GCaMP6s performed as well or better than Fura-2 in detecting agonist-induced calcium transients. We then examined the utility of GCaMP6s for continuously measuring apoptotic calcium release over the course of ten hours after treatment with staurosporine. We found that GCaMP6s was suitable for measuring apoptotic calcium release over long time courses and revealed significant heterogeneity in calcium release dynamics in individual cells challenged with staurosporine. Our results suggest GCaMP6s is an excellent indicator for monitoring long-term changes cytosolic calcium during apoptosis. PMID:28073595

Surface Pressure Dependencies in the GEOS-Chem-Adjoint System and the Impact of the GEOS-5 Surface Pressure on CO2 Model Forecast

NASA Technical Reports Server (NTRS)

Lee, Meemong; Weidner, Richard

2016-01-01

In the GEOS-Chem Adjoint (GCA) system, the total (wet) surface pressure of the GEOS meteorology is employed as dry surface pressure, ignoring the presence of water vapor. The Jet Propulsion Laboratory (JPL) Carbon Monitoring System (CMS) research team has been evaluating the impact of the above discrepancy on the CO2 model forecast and the CO2 flux inversion. The JPL CMS research utilizes a multi-mission assimilation framework developed by the Multi-Mission Observation Operator (M2O2) research team at JPL extending the GCA system. The GCA-M2O2 framework facilitates mission-generic 3D and 4D-variational assimilations streamlining the interfaces to the satellite data products and prior emission inventories. The GCA-M2O2 framework currently integrates the GCA system version 35h and provides a dry surface pressure setup to allow the CO2 model forecast to be performed with the GEOS-5 surface pressure directly or after converting it to dry surface pressure.

Surface Pressure Dependencies in the Geos-Chem-Adjoint System and the Impact of the GEOS-5 Surface Pressure on CO2 Model Forecast

NASA Technical Reports Server (NTRS)

Lee, Meemong; Weidner, Richard

2016-01-01

In the GEOS-Chem Adjoint (GCA) system, the total (wet) surface pressure of the GEOS meteorology is employed as dry surface pressure, ignoring the presence of water vapor. The Jet Propulsion Laboratory (JPL) Carbon Monitoring System (CMS) research team has been evaluating the impact of the above discrepancy on the CO2 model forecast and the CO2 flux inversion. The JPL CMS research utilizes a multi-mission assimilation framework developed by the Multi-Mission Observation Operator (M2O2) research team at JPL extending the GCA system. The GCA-M2O2 framework facilitates mission-generic 3D and 4D-variational assimilations streamlining the interfaces to the satellite data products and prior emission inventories. The GCA-M2O2 framework currently integrates the GCA system version 35h and provides a dry surface pressure setup to allow the CO2 model forecast to be performed with the GEOS-5 surface pressure directly or after converting it to dry surface pressure.

Giant cell arteritis and polymyalgia rheumatica: current challenges and opportunities.

PubMed

Dejaco, Christian; Brouwer, Elisabeth; Mason, Justin C; Buttgereit, Frank; Matteson, Eric L; Dasgupta, Bhaskar

2017-10-01

The fields of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) have advanced rapidly, resulting in a new understanding of these diseases. Fast-track strategies and improved awareness programmes that prevent irreversible sight loss through early diagnosis and treatment are a notable advance. Ultrasonography and other imaging techniques have been introduced into routine clinical practice and there have been promising reports on the efficacy of biologic agents, particularly IL-6 antagonists such as tocilizumab, in treating these conditions. Along with these developments, which should improve outcomes in patients with GCA and PMR, new questions and unmet needs have emerged; future research should address which pathogenetic mechanisms contribute to the different phases and clinical phenotypes of GCA, what role imaging has in the early diagnosis and monitoring of GCA and PMR, and in which patients and phases of these diseases novel biologic drugs should be used. This article discusses the implications of recent developments in our understanding of GCA and PMR, as well as the unmet needs concerning epidemiology, pathogenesis, imaging and treatment of these diseases.

Jasmine tea consumption and upper gastrointestinal cancer in China.

PubMed

Gao, Ying; Hu, Nan; Han, XiaoYou; Giffen, Carol; Ding, Ti; Goldstein, Alisa M; Taylor, Philip R

2009-12-01

Epidemiological data on green/jasmine tea and esophageal as well as gastric cancer are limited and inconclusive. In order to study the effect of jasmine tea in upper gastrointestinal (UGI) cancers, we evaluated 600 esophageal squamous cell carcinoma (ESCC), 598 gastric cardia cancer (GCA), and 316 gastric non-cardia cancer (GNCA) cases and 1,514 age-, gender-, and neighborhood-matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from logistic regression adjusted for matching factors and potential confounders. Among controls, 35% of males and 8% of females reported consumption of jasmine tea; other tea consumption was rare. Consumption of jasmine tea (ever vs. never) was not associated with risk of ESCC (OR = 1.15, 95% CI 0.92–1.44), GCA (OR = 1.14, 95% CI 0.88–1.37), or GNCA (OR = 0.85, 95% CI 0.64–1.15) in males and females combined. Among males, cumulative lifetime consumption showed a significant positive dose–response relation with ESCC risk, but not for GCA and GNCA. In exploratory analyses, occupation affected the relation between tea and ESCC such that consumption in males was associated with increased risk only in non-office workers. Overall, we found no evidence for a protective effect of tea in esophageal or gastric cancer. Further studies of the potential effects of thermal damage, tea quality, and water quality on UGI cancers are suggested.

Principal component analysis of dietary and lifestyle patterns in relation to risk of subtypes of esophageal and gastric cancer

PubMed Central

Silvera, Stephanie A. Navarro; Mayne, Susan T; Risch, Harvey A.; Gammon, Marilie D; Vaughan, Thomas; Chow, Wong-Ho; Dubin, Joel A; Dubrow, Robert; Schoenberg, Janet; Stanford, Janet L; West, A. Brian; Rotterdam, Heidrun; Blot, William J

2011-01-01

Purpose To perform pattern analyses of dietary and lifestyle factors in relation to risk of esophageal and gastric cancers. Methods We evaluated risk factors for esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and other gastric cancers (OGA) using data from a population-based case-control study conducted in Connecticut, New Jersey, and western Washington state. Dietary/lifestyle patterns were created using principal component analysis (PCA). Impact of the resultant scores on cancer risk was estimated through logistic regression. Results PCA identified six patterns: meat/nitrite, fruit/vegetable, smoking/alcohol, legume/meat alternate, GERD/BMI, and fish/vitamin C. Risk of each cancer under study increased with rising meat/nitrite score. Risk of EA increased with increasing GERD/BMI score, and risk of ESCC rose with increasing smoking/alcohol score and decreasing GERD/BMI score. Fruit/vegetable scores were inversely associated with EA, ESCC, and GCA. Conclusions PCA may provide a useful approach for summarizing extensive dietary/lifestyle data into fewer interpretable combinations that discriminate between cancer cases and controls. The analyses suggest that meat/nitrite intake is associated with elevated risk of each cancer under study, while fruit/vegetable intake reduces risk of EA, ESCC, and GCA. GERD/obesity were confirmed as risk factors for EA and smoking/alcohol as risk factors for ESCC. PMID:21435900

Neurodevelopmental origins of lifespan changes in brain and cognition

PubMed Central

Walhovd, Kristine B.; Krogsrud, Stine K.; Bartsch, Hauke; Bjørnerud, Atle; Due-Tønnessen, Paulina; Grydeland, Håkon; Hagler, Donald J.; Håberg, Asta K.; Kremen, William S.; Ferschmann, Lia; Nyberg, Lars; Panizzon, Matthew S.; Rohani, Darius A.; Skranes, Jon; Storsve, Andreas B.; Sølsnes, Anne Elisabeth; Tamnes, Christian K.; Thompson, Wesley K.; Reuter, Chase; Dale, Anders M.; Fjell, Anders M.

2016-01-01

Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4–88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother–Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain–cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course. PMID:27432992

Neurodevelopmental origins of lifespan changes in brain and cognition.

PubMed

Walhovd, Kristine B; Krogsrud, Stine K; Amlien, Inge K; Bartsch, Hauke; Bjørnerud, Atle; Due-Tønnessen, Paulina; Grydeland, Håkon; Hagler, Donald J; Håberg, Asta K; Kremen, William S; Ferschmann, Lia; Nyberg, Lars; Panizzon, Matthew S; Rohani, Darius A; Skranes, Jon; Storsve, Andreas B; Sølsnes, Anne Elisabeth; Tamnes, Christian K; Thompson, Wesley K; Reuter, Chase; Dale, Anders M; Fjell, Anders M

2016-08-16

Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4-88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother-Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain-cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course.

Giant-cell arteritis without cranial manifestations

PubMed Central

de Boysson, Hubert; Lambert, Marc; Liozon, Eric; Boutemy, Jonathan; Maigné, Gwénola; Ollivier, Yann; Ly, Kim; Manrique, Alain; Bienvenu, Boris; Aouba, Achille

2016-01-01

Abstract Diagnosis of giant-cell arteritis (GCA) is challenging in the absence of cardinal cranial symptoms/signs. We aimed to describe the clinical presentation, diagnostic process, and disease course of GCA patients without cranial symptoms, and to compare them to those of patients with typical cranial presentation. In this retrospective multicenter study, we enrolled patients with GCA who satisfied at least 3 of the 5 American College of Rheumatology criteria for GCA, or 2 criteria associated with contributory vascular biopsy other than temporal artery biopsy or with demonstration of large-vessel involvement; underwent iconographic evaluation of large arterial vessels (aortic CT scan or a positron emission tomography with 18F-fluorodeoxyglucose combined with computed tomography (FDG-PET/CT) scan or cardiac echography combined with a large-vessel Doppler) at diagnosis. We divided the cohort into 2 groups, distinguishing between patients without cranial symptoms/signs (i.e., headaches, clinical temporal artery anomaly, jaw claudication, ophthalmologic symptoms) and those with cranial symptoms/signs. In the entire cohort of 143 patients, all of whom underwent vascular biopsy and vascular imaging, we detected 31 (22%) patients with no cranial symptoms/signs. In the latter, diagnosis was biopsy proven in an arterial sample in 23 cases (74% of patients, on a temporal site in 20 cases and on an extratemporal site in 3). One-third of these 31 patients displayed extracranial symptoms/signs whereas the remaining two-thirds presented only with constitutional symptoms and/or inflammatory laboratory test results. Compared to the 112 patients with cardinal cranial clinical symptoms/signs, patients without cranial manifestations displayed lower levels of inflammatory laboratory parameters (C-reactive level: 68 [9–250] mg/L vs 120 [3–120] mg/L; P < 0.01), highest rate of aorta and aortic branch involvement identified (19/31 (61%) vs 42/112 (38%); P = 0.02) and also a lower rate of disease relapse (12/31 (39%) vs 67/112 (60%); P = 0.04). Our results suggest that patients without cranial symptoms/signs are prone to lower inflammatory laboratory parameters, fewer relapses, and more large-vessel involvement than those displaying cardinal cranial manifestations. Further studies are therefore required in order to determine whether these 2 subgroups of patients have a different prognosis, and therefore warrant different therapeutic and monitoring regimens. PMID:27367984

Old Receptors, New Treatment Strategies for Breast Cancer

DTIC Science & Technology

2012-04-01

48. Page DL, Gray R, Allred DC, Dressler LG, Hatfield AK, Martino S, et al. Prediction of node-negative breast cancer outcome by his- tologic grading...GCG GTC ACA GTG ACC TGC GAG GTC ACA GTG ACC TGC GAG GTC ACA GTG ACC TGC GA-30 and 50-AGC TTC GCA GGT CAC TGT GAC CTC GCA GGT CAC TGT GAC CTC GCA GGT...VS, Bobseine K, Gray Jr LE. Development and characterization of a cell line thatstablyexpresses anestrogen-responsive luciferase reporter

The Genetics Concept Assessment: a new concept inventory for gauging student understanding of genetics.

PubMed

Smith, Michelle K; Wood, William B; Knight, Jennifer K

2008-01-01

We have designed, developed, and validated a 25-question Genetics Concept Assessment (GCA) to test achievement of nine broad learning goals in majors and nonmajors undergraduate genetics courses. Written in everyday language with minimal jargon, the GCA is intended for use as a pre- and posttest to measure student learning gains. The assessment was reviewed by genetics experts, validated by student interviews, and taken by >600 students at three institutions. Normalized learning gains on the GCA were positively correlated with averaged exam scores, suggesting that the GCA measures understanding of topics relevant to instructors. Statistical analysis of our results shows that differences in the item difficulty and item discrimination index values between different questions on pre- and posttests can be used to distinguish between concepts that are well or poorly learned during a course.

The Genetics Concept Assessment: A New Concept Inventory for Gauging Student Understanding of Genetics

PubMed Central

Wood, William B.; Knight, Jennifer K.

2008-01-01

We have designed, developed, and validated a 25-question Genetics Concept Assessment (GCA) to test achievement of nine broad learning goals in majors and nonmajors undergraduate genetics courses. Written in everyday language with minimal jargon, the GCA is intended for use as a pre- and posttest to measure student learning gains. The assessment was reviewed by genetics experts, validated by student interviews, and taken by >600 students at three institutions. Normalized learning gains on the GCA were positively correlated with averaged exam scores, suggesting that the GCA measures understanding of topics relevant to instructors. Statistical analysis of our results shows that differences in the item difficulty and item discrimination index values between different questions on pre- and posttests can be used to distinguish between concepts that are well or poorly learned during a course. PMID:19047428

Genetically encoded calcium indicators for studying long-term calcium dynamics during apoptosis.

PubMed

Garcia, M Iveth; Chen, Jessica J; Boehning, Darren

2017-01-01

Intracellular calcium release is essential for regulating almost all cellular functions. Specific spatio-temporal patterns of cytosolic calcium elevations are critical determinants of cell fate in response to pro-apoptotic cellular stressors. As the apoptotic program can take hours or days, measurement of long-term calcium dynamics are essential for understanding the mechanistic role of calcium in apoptotic cell death. Due to the technical limitations of using calcium-sensitive dyes to measure cytosolic calcium little is known about long-term calcium dynamics in living cells after treatment with apoptosis-inducing drugs. Genetically encoded calcium indicators could potentially overcome some of the limitations of calcium-sensitive dyes. Here, we compared the performance of the genetically encoded calcium indicators GCaMP6s and GCaMP6f with the ratiometric dye Fura-2. GCaMP6s performed as well or better than Fura-2 in detecting agonist-induced calcium transients. We then examined the utility of GCaMP6s for continuously measuring apoptotic calcium release over the course of ten hours after treatment with staurosporine. We found that GCaMP6s was suitable for measuring apoptotic calcium release over long time courses and revealed significant heterogeneity in calcium release dynamics in individual cells challenged with staurosporine. Our results suggest GCaMP6s is an excellent indicator for monitoring long-term changes cytosolic calcium during apoptosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Natriuretic Peptide Receptor Guanylyl Cyclase-A in Podocytes is Renoprotective but Dispensable for Physiologic Renal Function.

PubMed

Staffel, Janina; Valletta, Daniela; Federlein, Anna; Ehm, Katharina; Volkmann, Regine; Füchsl, Andrea M; Witzgall, Ralph; Kuhn, Michaela; Schweda, Frank

2017-01-01

The cardiac natriuretic peptides (NPs), atrial NP and B-type NP, regulate fluid homeostasis and arterial BP through renal actions involving increased GFR and vascular and tubular effects. Guanylyl cyclase-A (GC-A), the transmembrane cGMP-producing receptor shared by these peptides, is expressed in different renal cell types, including podocytes, where its function is unclear. To study the effects of NPs on podocytes, we generated mice with a podocyte-specific knockout of GC-A (Podo-GC-A KO). Despite the marked reduction of GC-A mRNA in GC-A KO podocytes to 1% of the control level, Podo-GC-A KO mice and control littermates did not differ in BP, GFR, or natriuresis under baseline conditions. Moreover, infusion of synthetic NPs similarly increased the GFR and renal perfusion in both genotypes. Administration of the mineralocorticoid deoxycorticosterone-acetate (DOCA) in combination with high salt intake induced arterial hypertension of similar magnitude in Podo-GC-A KO mice and controls. However, only Podo-GC-A KO mice developed massive albuminuria (controls: 35-fold; KO: 5400-fold versus baseline), hypoalbuminemia, reduced GFR, and marked glomerular damage. Furthermore, DOCA treatment led to decreased expression of the slit diaphragm-associated proteins podocin, nephrin, and synaptopodin and to enhanced transient receptor potential canonical 6 (TRPC6) channel expression and ATP-induced calcium influx in podocytes of Podo-GC-A KO mice. Concomitant treatment of Podo-GC-A KO mice with the TRPC channel blocker SKF96365 markedly ameliorated albuminuria and glomerular damage in response to DOCA. In conclusion, the physiologic effects of NPs on GFR and natriuresis do not involve podocytes. However, NP/GC-A/cGMP signaling protects podocyte integrity under pathologic conditions, most likely by suppression of TRPC channels. Copyright © 2016 by the American Society of Nephrology.

Polymorphism of A133S and promoter hypermethylation in Ras association domain family 1A gene (RASSF1A) is associated with risk of esophageal and gastric cardia cancers in Chinese population from high incidence area in northern China.

PubMed

Zhou, Sheng Li; Cui, Juan; Fan, Zong Min; Li, Xue Min; Li, Ji Lin; Liu, Bao Chi; Zhang, Dong Yun; Liu, Hong Yan; Zhao, Xue Ke; Song, Xin; Wang, Ran; Yan, Ze Chen; Yi, Hui Xing; Wang, Li Dong

2013-05-25

The role of tumor suppressor gene RASSF1A in the esophageal and gastric cardia carcinogenesis is still inconclusive. In this study, the polymorphism, promoter methylation and gene expression of RASSF1A were characterized in esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA). We firstly analyzed the prevalence of RASSF1A A133S in a total of 228 cancer patients with ESCC (n=112) and GCA (n=116) and 235 normal controls by polymerase chain reaction (PCR) and restriction enzyme-digestion assay. Then, the promoter methylation status of the RASSF1A in ESCC (n=143), GCA (n=92) and corresponding adjacent normal tissues were further investigated using methylation-specific PCR (MSP) approach. Finally, the RASSF1A protein expression were determined in ESCC (n=27), GCA (n=24) and the matched adjacent normal tissues by immunohistochemical method. The frequency of 133Ala/Se and Ser/Ser genotype was significantly higher in GCA patients than in normal controls (19.0% vs. 10.2%, P=0.02). Compared with Ala/Ala genotype, Ala/Se and Ser/Ser genotype significantly increased susceptibility to GCA (OR=2.06, 95% CI=1.09-3.97). However, this polymorphism had no association with ESCC (P=0.69). The promoter methylation of RASSF1A gene was significantly increased the risk to both ESCC (OR=5.90, 95% CI=2.78-12.52) and GCA (OR=7.50, 95% CI= 2.78-20.23). Promoter methylation of RASSF1A gene in ESCC was also associated with age and cancer cell differentiation (for age: OR=3.11, 95% CI=1.10-8.73; for differentiation: OR=0.29, 95% CI=0.12-0.69). RASSF1A positive expression was significantly decreased the risk of GCA (OR=0.16, 95% CI=0.03-0.83). In contrast, there was no statistical significance between RASSF1A positive expression and ESCC. The expression of RASSF1A protein trend to be positively related with older GCA patients (OR=16.20, 95% CI=1.57-167.74). The present findings suggest that alterations of RASSF1A may play an important role in gastric cardia carcinogenesis in terms of polymorphism, promoter hypermethylation and protein expression. Whereas, RASSF1A hypermethylation may probably also be involved in esophageal squamous cell carcinogenesis.

Crystallization and preliminary X-ray characterization of the genetically encoded fluorescent calcium indicator protein GCaMP2

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

Rodríguez Guilbe, María M.; Protein Research and Development Center, University of Puerto Rico; Alfaro Malavé, Elisa C.

The genetically encoded fluorescent calcium-indicator protein GCaMP2 was crystallized in the calcium-saturated form. X-ray diffraction data were collected to 2.0 Å resolution and the structure was solved by molecular replacement. Fluorescent proteins and their engineered variants have played an important role in the study of biology. The genetically encoded calcium-indicator protein GCaMP2 comprises a circularly permuted fluorescent protein coupled to the calcium-binding protein calmodulin and a calmodulin target peptide, M13, derived from the intracellular calmodulin target myosin light-chain kinase and has been used to image calcium transients in vivo. To aid rational efforts to engineer improved variants of GCaMP2, thismore » protein was crystallized in the calcium-saturated form. X-ray diffraction data were collected to 2.0 Å resolution. The crystals belong to space group C2, with unit-cell parameters a = 126.1, b = 47.1, c = 68.8 Å, β = 100.5° and one GCaMP2 molecule in the asymmetric unit. The structure was phased by molecular replacement and refinement is currently under way.« less

Giant Cell Arteritis of the Female Genital Tract With Occult Temporal Arteritis and Marginal Zone Lymphoma Harboring Novel 20q Deletion: A Case Report and Literature Review.

PubMed

Pradhan, Dinesh; Amin, Rajnikant M; Jones, Miroslawa W; Surti, Urvashi; Parwani, Anil V

2016-02-01

Giant cell arteritis (GCA) is an immunologically mediated vasculitis of large and medium-sized vessels, typically affecting the cranial arteries and usually occurring in the elderly. GCA of the female genital tract is extremely rare with only 31 cases reported in the English literature. An 83-year-old white female with postmenopausal vaginal bleeding revealed an endometrial polyp on pelvic ultrasonography following which polypectomy and subsequently hysterectomy with bilateral salpingo-oophorectomy was done. Microscopy revealed a well-differentiated endometrioid adenocarcinoma. Interestingly, classic GCA involving numerous small to medium-sized arteries of the cervix, myometrium, bilateral fallopian tubes, and ovaries was also identified. Hematologic evaluation revealed marginal zone lymphoma with an exceptionally rare 20q deletion. Bilateral temporal artery biopsy was done subsequently, which exhibited GCA on microscopy. Corticosteroid was started that improved her polymyalgia rheumatica symptoms. The patient is on follow-up for 3 years and is doing well. To our knowledge, this is the first case of GCA of the female genital tract associated with a lymphoma and the second case of marginal zone lymphoma with the novel 20q deletion. © The Author(s) 2015.

Gene encoding γ-carbonic anhydrase is cotranscribed with argC and induced in response to stationary phase and high CO2 in Azospirillum brasilense Sp7

PubMed Central

2010-01-01

Background Carbonic anhydrase (CA) is a ubiquitous enzyme catalyzing the reversible hydration of CO2 to bicarbonate, a reaction underlying diverse biochemical and physiological processes. Gamma class carbonic anhydrases (γ-CAs) are widespread in prokaryotes but their physiological roles remain elusive. At present, only γ-CA of Methanosarcina thermophila (Cam) has been shown to have CA activity. Genome analysis of a rhizobacterium Azospirillum brasilense, revealed occurrence of ORFs encoding one β-CA and two γ-CAs. Results One of the putative γ-CA encoding genes of A. brasilense was cloned and overexpressed in E. coli. Electrometric assays for CA activity of the whole cell extracts overexpressing recombinant GCA1 did not show CO2 hydration activity. Reverse transcription-PCR analysis indicated that gca1 in A. brasilense is co-transcribed with its upstream gene annotated as argC, which encodes a putative N-acetyl-γ-glutamate-phosphate reductase. 5'-RACE also demonstrated that there was no transcription start site between argC and gca1, and the transcription start site located upstream of argC transcribed both the genes (argC-gca1). Using transcriptional fusions of argC-gca1 upstream region with promoterless lacZ, we further demonstrated that gca1 upstream region did not have any promoter and its transcription occurred from a promoter located in the argC upstream region. The transcription of argC-gca1 operon was upregulated in stationary phase and at elevated CO2 atmosphere. Conclusions This study shows lack of CO2 hydration activity in a recombinant protein expressed from a gene predicted to encode a γ-carbonic anhydrase in A. brasilense although it cross reacts with anti-Cam antibody raised against a well characterized γ-CA. The organization and regulation of this gene along with the putative argC gene suggests its involvement in arginine biosynthetic pathway instead of the predicted CO2 hydration. PMID:20598158

Gene encoding gamma-carbonic anhydrase is cotranscribed with argC and induced in response to stationary phase and high CO2 in Azospirillum brasilense Sp7.

PubMed

Kaur, Simarjot; Mishra, Mukti N; Tripathi, Anil K

2010-07-04

Carbonic anhydrase (CA) is a ubiquitous enzyme catalyzing the reversible hydration of CO2 to bicarbonate, a reaction underlying diverse biochemical and physiological processes. Gamma class carbonic anhydrases (gamma-CAs) are widespread in prokaryotes but their physiological roles remain elusive. At present, only gamma-CA of Methanosarcina thermophila (Cam) has been shown to have CA activity. Genome analysis of a rhizobacterium Azospirillum brasilense, revealed occurrence of ORFs encoding one beta-CA and two gamma-CAs. One of the putative gamma-CA encoding genes of A. brasilense was cloned and overexpressed in E. coli. Electrometric assays for CA activity of the whole cell extracts overexpressing recombinant GCA1 did not show CO2 hydration activity. Reverse transcription-PCR analysis indicated that gca1 in A. brasilense is co-transcribed with its upstream gene annotated as argC, which encodes a putative N-acetyl-gamma-glutamate-phosphate reductase. 5'-RACE also demonstrated that there was no transcription start site between argC and gca1, and the transcription start site located upstream of argC transcribed both the genes (argC-gca1). Using transcriptional fusions of argC-gca1 upstream region with promoterless lacZ, we further demonstrated that gca1 upstream region did not have any promoter and its transcription occurred from a promoter located in the argC upstream region. The transcription of argC-gca1 operon was upregulated in stationary phase and at elevated CO2 atmosphere. This study shows lack of CO2 hydration activity in a recombinant protein expressed from a gene predicted to encode a gamma-carbonic anhydrase in A. brasilense although it cross reacts with anti-Cam antibody raised against a well characterized gamma-CA. The organization and regulation of this gene along with the putative argC gene suggests its involvement in arginine biosynthetic pathway instead of the predicted CO2 hydration.

Recent advances in our understanding of giant cell arteritis pathogenesis.

PubMed

Samson, Maxime; Corbera-Bellalta, Marc; Audia, Sylvain; Planas-Rigol, Ester; Martin, Laurent; Cid, Maria Cinta; Bonnotte, Bernard

2017-08-01

Giant cell arteritis (GCA) is a granulomatous vasculitis affecting large arteries, especially the aorta and the extracranial branches of the external carotid artery. Its exact pathogenesis is not fully understood but major progress has been made in recent years, leading to new therapeutic targets like inhibition of the interleukin-6 pathway or the modulation of immune checkpoints. The cause of GCA has not been clearly identified but it is thought that GCA occurs on a genetic background and is triggered by unknown environmental factors that could activate and lead to the maturation of dendritic cells localized in the adventitia of normal arteries. These activated dendritic cells then produce chemokines which trigger the recruitment of CD4 + T cells, which in turn become activated, proliferate and polarize into Th1 and Th17 cells, which produce IFN-γ and IL-17, respectively. Exposed to IFN-γ, endothelial cells and vascular smooth muscle cells produce chemokines leading to the recruitment of further Th1 cells, CD8 + T cells and monocytes. The latter differentiate into macrophages, which, when persistently exposed to IFN-γ, form giant cells, the histological hallmark of GCA. With the contribution of vascular smooth muscle cells, immune cells then trigger the destruction and remodeling of the arterial wall, thus leading to the formation of a neo-intima resulting in progressive occlusion of the arterial lumen, which is responsible for the ischemic symptoms of GCA. In this paper, we review recent progress in our understanding of GCA pathogenesis in the fields of genetics, epigenetics, infections, immunology and vascular remodeling. Copyright © 2017 Elsevier B.V. All rights reserved.

Gastric atrophy and risk of oesophageal cancer and gastric cardia adenocarcinoma--a systematic review and meta-analysis.

PubMed

Islami, F; Sheikhattari, P; Ren, J S; Kamangar, F

2011-04-01

Several studies have reported an association between gastric atrophy and upper gastrointestinal cancers. Our aim was to summarise the available information and calculate the relative risks (RRs) associated with gastric atrophy for gastric cardia adenocarcinoma (GCA), oesophageal squamous cell carcinoma (OSCC), and oesophageal adenocarcinoma (OAC) by conducting a systematic review and meta-analysis. We searched the PubMed and ISI-Web of Science databases, as well as the reference lists of the relevant articles. Summary RRs and 95% confidence intervals (95% CI) were calculated using random-effects models for the association between gastric atrophy, defined histologically or by serum pepsinogen markers, and OSCC, OAC, and GCA. Eighteen articles were included in the meta-analysis; 13, 7, and 3 studies reported on GCA, OSCC, and OAC, respectively. The overall RRs (95% CI) for the three cancer types were: GCA, 2.89 (2.09-3.98); OSCC, 1.94 (1.48-2.55); OAC, 0.51 (0.19-1.37). Several subgroup analyses showed the robustness of the results. In the majority of the analyses, there was low to moderate heterogeneity. This study found two- to threefold increased risk of OSCC and GCA but a possible reduced risk of OAC in people with gastric atrophy. Further studies are needed to establish the association with OAC and causal association with OSCC, and mechanisms of the increased risk need to be investigated for GCA. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Development of Effective Connectivity during Own- and Other-Race Face Processing: A Granger Causality Analysis

PubMed Central

Zhou, Guifei; Liu, Jiangang; Ding, Xiao Pan; Fu, Genyue; Lee, Kang

2016-01-01

Numerous developmental studies have suggested that other-race effect (ORE) in face recognition emerges as early as in infancy and develops steadily throughout childhood. However, there is very limited research on the neural mechanisms underlying this developmental ORE. The present study used Granger causality analysis (GCA) to examine the development of children's cortical networks in processing own- and other-race faces. Children were between 3 and 13 years. An old-new paradigm was used to assess their own- and other-race face recognition with ETG-4000 (Hitachi Medical Co., Japan) acquiring functional near infrared spectroscopy (fNIRS) data. After preprocessing, for each participant and under each face condition, we obtained the causal map by calculating the weights of causal relations between the time courses of [oxy-Hb] of each pair of channels using GCA. To investigate further the differential causal connectivity for own-race faces and other-race faces at the group level, a repeated measure analysis of variance (ANOVA) was performed on the GCA weights for each pair of channels with the face race task (own-race face vs. other-race face) as the within-subject variable and the age as a between-subject factor (continuous variable). We found an age-related increase in functional connectivity, paralleling a similar age-related improvement in behavioral face processing ability. More importantly, we found that the significant differences in neural functional connectivity between the recognition of own-race faces and that of other-race faces were modulated by age. Thus, like the behavioral ORE, the neural ORE emerges early and undergoes a protracted developmental course. PMID:27713696

6DOF Testing of the SLS Inertial Navigation Unit

NASA Technical Reports Server (NTRS)

Geohagan, Kevin; Bernard, Bill; Oliver, T. Emerson; Leggett, Jared; Strickland, Dennis

2018-01-01

The Navigation System on the NASA Space Launch System (SLS) Block 1 vehicle performs initial alignment of the Inertial Navigation System (INS) navigation frame through gyrocompass alignment (GCA). Because the navigation architecture for the SLS Block 1 vehicle is a purely inertial system, the accuracy of the achieved orbit relative to mission requirements is very sensitive to initial alignment accuracy. The assessment of this sensitivity and many others via simulation is a part of the SLS Model-Based Design and Model-Based Requirements approach. As a part of the aforementioned, 6DOF Monte Carlo simulation is used in large part to develop and demonstrate verification of program requirements. To facilitate this and the GN&C flight software design process, an SLS-Program-controlled Design Math Model (DMM) of the SLS INS was developed by the SLS Navigation Team. The SLS INS model implements all of the key functions of the hardware-namely, GCA, inertial navigation, and FDIR (Fault Detection, Isolation, and Recovery)-in support of SLS GN&C design requirements verification. Despite the strong sensitivity to initial alignment, GCA accuracy requirements were not verified by test due to program cost and schedule constraints. Instead, the system relies upon assessments performed using the SLS INS model. In order to verify SLS program requirements by analysis, the SLS INS model is verified and validated against flight hardware. In lieu of direct testing of GCA accuracy in support of requirement verification, the SLS Navigation Team proposed and conducted an engineering test to, among other things, validate the GCA performance and overall behavior of the SLS INS model through comparison with test data. This paper will detail dynamic hardware testing of the SLS INS, conducted by the SLS Navigation Team at Marshall Space Flight Center's 6DOF Table Facility, in support of GCA performance characterization and INS model validation. A 6-DOF motion platform was used to produce 6DOF pad twist and sway dynamics while a simulated SLS flight computer communicated with the INS. Tests conducted include an evaluation of GCA algorithm robustness to increasingly dynamic pad environments, an examination of GCA algorithm stability and accuracy over long durations, and a long-duration static test to gather enough data for Allan Variance analysis. Test setup, execution, and data analysis will be discussed, including analysis performed in support of SLS INS model validation.

Altered effective connectivity of default model brain network underlying amnestic MCI

NASA Astrophysics Data System (ADS)

Yan, Hao; Wang, Yonghui; Tian, Jie

2012-02-01

Mild cognitive impairment (MCI) is the transitional, heterogeneous continuum from healthy elderly to Alzheimer's disease (AD). Previous studies have shown that brain functional activity in the default mode network (DMN) is impaired in MCI patients. However, the altered effective connectivity of the DMN in MCI patients remains largely unknown. The present study combined an independent component analysis (ICA) approach with Granger causality analysis (mGCA) to investigate the effective connectivity within the DMN in 12 amnestic MCI patients and 12 age-matched healthy elderly. Compared to the healthy control, the MCI exhibited decreased functional activity in the posterior DMN regions, as well as a trend towards activity increases in anterior DMN regions. Results from mGCA further supported this conclusion that the causal influence projecting to the precuneus/PCC became much weaker in MCI, while stronger interregional interactions emerged within the frontal-parietal cortices. These findings suggested that abnormal effective connectivity within the DMN may elucidate the dysfunctional and compensatory processes in MCI brain networks.

Studying the mechanism of neurostimulation by infrared laser light using GCaMP6s and Rhodamine B imaging

NASA Astrophysics Data System (ADS)

Moreau, David; Lefort, Claire; Bardet, Sylvia M.; O'Connor, Rodney P.

2016-03-01

Infrared laser light radiation can be used to depolarize neurons and to stimulate neural activity. The absorption of infrared radiation and heating of biological tissue is thought to be the underlying mechanism of this phenomenon whereby local temperature increases in the plasma membrane of cells either directly influence membrane properties or act via temperature sensitive ion channels. Action potentials are typically measured electrically in neurons with microelectrodes, but they can also be observed using fluorescence microscopy techniques that use synthetic or genetically encoded calcium indicators. In this work, we studied the impact of infrared laser light on neuronal calcium signals to address the mechanism of these thermal effects. Cultured primary mouse hippocampal neurons expressing the genetically encoded calcium indicator GCaMP6s were used in combination with the temperature sensitive fluorophore Rhodamine B to measure calcium signals and temperature changes at the cellular level. Here we present our all-optical strategy for studying the influence of infrared laser light on neuronal activity.

Optimism, community attachment and serostatus disclosure among HIV-positive men who have sex with men.

PubMed

Murphy, Patrick J; Hevey, David; O'Dea, Siobhán; Ní Rathaille, Neans; Mulcahy, Fiona

2015-01-01

This study investigated the relationship between HIV health optimism (HHO) (the belief that health will remain good after HIV infection due to treatment efficacy), HIV-positive community attachment (HCA), gay community attachment (GCA) and serostatus disclosure to casual sex partners by HIV-positive men who have sex with men (MSM). Cross-sectional questionnaire data were gathered from 97 HIV-positive MSM attending an HIV treatment clinic in Dublin, Ireland. Based on self-reported disclosure to casual partners, participants were classified according to their pattern of disclosure (consistent, inconsistent or non-disclosers). Multinomial logistic regression was used to assess HHO, HCA and GCA as predictors of participants' pattern of disclosure. Classification as a non-discloser (compared to a consistent discloser) was associated with higher HHO, less HCA and greater GCA. Classification as an inconsistent discloser (compared to a consistent discloser) was associated with higher GCA. The study provided novel quantitative evidence for associations between the constructs of interest. The results suggest that (1) HHO is associated with reduced disclosure, suggesting optimism may preclude individuals reaping the benefits of serostatus disclosure and (2) HCA and GCA represent competing attachments with conflicting effects on disclosure behaviour. Limitations and areas for future research are discussed.

Crystal structures of the GCaMP calcium sensor reveal the mechanism of fluorescence signal change and aid rational design.

PubMed

Akerboom, Jasper; Rivera, Jonathan D Vélez; Guilbe, María M Rodríguez; Malavé, Elisa C Alfaro; Hernandez, Hector H; Tian, Lin; Hires, S Andrew; Marvin, Jonathan S; Looger, Loren L; Schreiter, Eric R

2009-03-06

The genetically encoded calcium indicator GCaMP2 shows promise for neural network activity imaging, but is currently limited by low signal-to-noise ratio. We describe x-ray crystal structures as well as solution biophysical and spectroscopic characterization of GCaMP2 in the calcium-free dark state, and in two calcium-bound bright states: a monomeric form that dominates at intracellular concentrations observed during imaging experiments and an unexpected domain-swapped dimer with decreased fluorescence. This series of structures provides insight into the mechanism of Ca2+-induced fluorescence change. Upon calcium binding, the calmodulin (CaM) domain wraps around the M13 peptide, creating a new domain interface between CaM and the circularly permuted enhanced green fluorescent protein domain. Residues from CaM alter the chemical environment of the circularly permuted enhanced green fluorescent protein chromophore and, together with flexible inter-domain linkers, block solvent access to the chromophore. Guided by the crystal structures, we engineered a series of GCaMP2 point mutants to probe the mechanism of GCaMP2 function and characterized one mutant with significantly improved signal-to-noise. The mutation is located at a domain interface and its effect on sensor function could not have been predicted in the absence of structural data.

Differential Effects of the Putative GBF1 Inhibitors Golgicide A and AG1478 on Enterovirus Replication▿

PubMed Central

van der Linden, Lonneke; van der Schaar, Hilde M.; Lanke, Kjerstin H. W.; Neyts, Johan; van Kuppeveld, Frank J. M.

2010-01-01

The genus Enterovirus, belonging to the family Picornaviridae, includes well-known pathogens, such as poliovirus, coxsackievirus, and rhinovirus. Brefeldin A (BFA) impedes replication of several enteroviruses through inhibition of Golgi-specific BFA resistance factor 1 (GBF1), a regulator of secretory pathway integrity and transport. GBF1 mediates the GTP exchange of Arf1, which in activated form recruits coatomer protein complex I (COP-I) to Golgi vesicles, a process important in transport between the endoplasmic reticulum and Golgi vesicles. Recently, the drugs AG1478 and Golgicide A (GCA) were put forward as new inhibitors of GBF1. In this study, we investigated the effects of these putative GBF1 inhibitors on secretory pathway function and enterovirus replication. We show that both drugs induced fragmentation of the Golgi vesicles and caused dissociation of Arf1 and COP-I from Golgi membranes, yet they differed in their effect on GBF1 localization. The effects of AG1478, but not those of GCA, could be countered by overexpression of Arf1, indicating a difference in their molecular mechanism of action. Consistent with this idea, we observed that GCA drastically reduced replication of coxsackievirus B3 (CVB3) and other human enterovirus species, whereas AG1478 had no effect at all on enterovirus replication. Time-of-addition studies and analysis of RNA replication using a subgenomic replicon both showed that GCA suppresses RNA replication of CVB3, which could be countered by overexpression of GBF1. These results indicate that, in contrast to AG1478, GCA inhibits CVB3 RNA replication by targeting GBF1. AG1478 and GCA may be valuable tools to further dissect enterovirus replication. PMID:20504936

Helicobacter pylori dupA and gastric acid secretion are negatively associated with gastric cancer development.

PubMed

Imagawa, Shinobu; Ito, Masanori; Yoshihara, Masaharu; Eguchi, Hidetaka; Tanaka, Shinji; Chayama, Kazuaki

2010-12-01

Few reports have described the cancer prevalence of peptic ulcer patients with long-term follow-up studies. We have conducted a long-term retrospective cohort study of Japanese peptic ulcer patients and evaluated the risk factors for the occurrence of gastric cancer (GCa). A total of 136 patients diagnosed with peptic ulcers from 1975 to 1983 were enrolled. These 136 cases [102 males and 34 females; 69 gastric ulcer (GU) and 67 duodenal ulcer (DU) patients at the time of enrollment; mean follow-up period of 14.4 years (range 1-30 years)] after being matched with a tumour registry database in Hiroshima prefecture were surveyed for GCa. We investigated Helicobacter pylori duodenal ulcer promoter gene A (dupA) using paraffin-embedded gastric biopsy specimens in 56 cases. Gastric acid secretion and basal acid output (BAO) in 40 cases, and maximal acid output in 68 cases, had been measured at first diagnosis of peptic ulcers. GCa was detected in 24 patients (17 with GU, 7 with DU) during the follow-up. The prevalence of GCa was significantly higher in GU patients than in DU patients (log-rank test P<0.05). dupA-positive H. pylori was detected not only in DU patients (9/20) but also in GU patients (9/36). Gastric acid output was significantly larger in quantity in patients with dupA-positive H. pylori than in those with dupA-negative H. pylori (P<0.05). The occurrence of GCa was significantly lower in patients with dupA-positive H. pylori and a high BAO level (log-rank test P<0.05). DUs, higher acid output and dupA-positive H. pylori were negatively associated with GCa.

Functional connectivity structure of cortical calcium dynamics in anesthetized and awake mice.

PubMed

Wright, Patrick W; Brier, Lindsey M; Bauer, Adam Q; Baxter, Grant A; Kraft, Andrew W; Reisman, Matthew D; Bice, Annie R; Snyder, Abraham Z; Lee, Jin-Moo; Culver, Joseph P

2017-01-01

The interplay between hemodynamic-based markers of cortical activity (e.g. fMRI and optical intrinsic signal imaging), which are an indirect and relatively slow report of neural activity, and underlying synaptic electrical and metabolic activity through neurovascular coupling is a topic of ongoing research and debate. As application of resting state functional connectivity measures is extended further into topics such as brain development, aging and disease, the importance of understanding the fundamental physiological basis for functional connectivity will grow. Here we extend functional connectivity analysis from hemodynamic- to calcium-based imaging. Transgenic mice (n = 7) expressing a fluorescent calcium indicator (GCaMP6) driven by the Thy1 promoter in glutamatergic neurons were imaged transcranially in both anesthetized (using ketamine/xylazine) and awake states. Sequential LED illumination (λ = 454, 523, 595, 640nm) enabled concurrent imaging of both GCaMP6 fluorescence emission (corrected for hemoglobin absorption) and hemodynamics. Functional connectivity network maps were constructed for infraslow (0.009-0.08Hz), intermediate (0.08-0.4Hz), and high (0.4-4.0Hz) frequency bands. At infraslow and intermediate frequencies, commonly used in BOLD fMRI and fcOIS studies of functional connectivity and implicated in neurovascular coupling mechanisms, GCaMP6 and HbO2 functional connectivity structures were in high agreement, both qualitatively and also quantitatively through a measure of spatial similarity. The spontaneous dynamics of both contrasts had the highest correlation when the GCaMP6 signal was delayed with a ~0.6-1.5s temporal offset. Within the higher-frequency delta band, sensitive to slow wave sleep oscillations in non-REM sleep and anesthesia, we evaluate the speed with which the connectivity analysis stabilized and found that the functional connectivity maps captured putative network structure within time window lengths as short as 30 seconds. Homotopic GCaMP6 functional connectivity maps at 0.4-4.0Hz in the anesthetized states show a striking correlated and anti-correlated structure along the anterior to posterior axis. This structure is potentially explained in part by observed propagation of delta-band activity from frontal somatomotor regions to visuoparietal areas. During awake imaging, this spatio-temporal quality is altered, and a more complex and detailed functional connectivity structure is observed. The combined calcium/hemoglobin imaging technique described here will enable the dissociation of changes in ionic and hemodynamic functional structure and neurovascular coupling and provide a framework for subsequent studies of neurological disease such as stroke.

Functional connectivity structure of cortical calcium dynamics in anesthetized and awake mice

PubMed Central

Wright, Patrick W.; Brier, Lindsey M.; Bauer, Adam Q.; Baxter, Grant A.; Kraft, Andrew W.; Reisman, Matthew D.; Bice, Annie R.; Snyder, Abraham Z.; Lee, Jin-Moo; Culver, Joseph P.

2017-01-01

The interplay between hemodynamic-based markers of cortical activity (e.g. fMRI and optical intrinsic signal imaging), which are an indirect and relatively slow report of neural activity, and underlying synaptic electrical and metabolic activity through neurovascular coupling is a topic of ongoing research and debate. As application of resting state functional connectivity measures is extended further into topics such as brain development, aging and disease, the importance of understanding the fundamental physiological basis for functional connectivity will grow. Here we extend functional connectivity analysis from hemodynamic- to calcium-based imaging. Transgenic mice (n = 7) expressing a fluorescent calcium indicator (GCaMP6) driven by the Thy1 promoter in glutamatergic neurons were imaged transcranially in both anesthetized (using ketamine/xylazine) and awake states. Sequential LED illumination (λ = 454, 523, 595, 640nm) enabled concurrent imaging of both GCaMP6 fluorescence emission (corrected for hemoglobin absorption) and hemodynamics. Functional connectivity network maps were constructed for infraslow (0.009–0.08Hz), intermediate (0.08–0.4Hz), and high (0.4–4.0Hz) frequency bands. At infraslow and intermediate frequencies, commonly used in BOLD fMRI and fcOIS studies of functional connectivity and implicated in neurovascular coupling mechanisms, GCaMP6 and HbO2 functional connectivity structures were in high agreement, both qualitatively and also quantitatively through a measure of spatial similarity. The spontaneous dynamics of both contrasts had the highest correlation when the GCaMP6 signal was delayed with a ~0.6–1.5s temporal offset. Within the higher-frequency delta band, sensitive to slow wave sleep oscillations in non-REM sleep and anesthesia, we evaluate the speed with which the connectivity analysis stabilized and found that the functional connectivity maps captured putative network structure within time window lengths as short as 30 seconds. Homotopic GCaMP6 functional connectivity maps at 0.4–4.0Hz in the anesthetized states show a striking correlated and anti-correlated structure along the anterior to posterior axis. This structure is potentially explained in part by observed propagation of delta-band activity from frontal somatomotor regions to visuoparietal areas. During awake imaging, this spatio-temporal quality is altered, and a more complex and detailed functional connectivity structure is observed. The combined calcium/hemoglobin imaging technique described here will enable the dissociation of changes in ionic and hemodynamic functional structure and neurovascular coupling and provide a framework for subsequent studies of neurological disease such as stroke. PMID:29049297

Crystallization and preliminary X-ray characterization of the genetically encoded fluorescent calcium indicator protein GCaMP2

PubMed Central

Rodríguez Guilbe, María M.; Alfaro Malavé, Elisa C.; Akerboom, Jasper; Marvin, Jonathan S.; Looger, Loren L.; Schreiter, Eric R.

2008-01-01

Fluorescent proteins and their engineered variants have played an important role in the study of biology. The genetically encoded calcium-indicator protein GCaMP2 comprises a circularly permuted fluorescent protein coupled to the calcium-binding protein calmodulin and a calmodulin target peptide, M13, derived from the intracellular calmodulin target myosin light-chain kinase and has been used to image calcium transients in vivo. To aid rational efforts to engineer improved variants of GCaMP2, this protein was crystallized in the calcium-saturated form. X-ray diffraction data were collected to 2.0 Å resolution. The crystals belong to space group C2, with unit-cell parameters a = 126.1, b = 47.1, c = 68.8 Å, β = 100.5° and one GCaMP2 molecule in the asymmetric unit. The structure was phased by molecular replacement and refinement is currently under way. PMID:18607093

Glucocorticoids for Management of Polymyalgia Rheumatica and Giant Cell Arteritis.

PubMed

Matteson, Eric L; Buttgereit, Frank; Dejaco, Christian; Dasgupta, Bhaskar

2016-02-01

Diagnosis of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) is based on typical clinical, histologic, and laboratory features. Ultrasonographic imaging in PMR with assessment especially of subdeltoid bursitis can aid in diagnosis and in following response to treatment. In GCA, diagnosis and disease activity are supported with ultrasonographic, MRI, or [(18)F]fluorodeoxyglucose PET evaluation of large vessels. Glucocorticoids are the primary therapy for PMR and GCA. Methotrexate may be used in patients at high risk for glucocorticoid adverse effects and patients with frequent relapse or needing protracted therapy. Other therapeutic approaches including interleukin 6 antagonists are under evaluation. Copyright © 2016 Elsevier Inc. All rights reserved.

Geographical and genetic factors do not account for significant differences in the clinical spectrum of giant cell arteritis in southern europe.

PubMed

Gonzalez-Gay, Miguel A; Boiardi, Luigi; Garcia-Porrua, Carlos; Macchioni, Pierluigi; Amor-Dorado, Juan C; Salvarani, Carlo

2004-03-01

To investigate whether genetic and geographical differences may influence the clinical spectrum of giant cell arteritis (GCA), we compared the demographic and clinical features of patients with biopsy-proven GCA from Reggio Emilia (Northern Italy) and Lugo (Northwest Spain) during a 15-year period. We performed a retrospective review of the case records of all patients diagnosed with biopsy-proven GCA at Hospital Xeral-Calde (Lugo, Spain) and Hospital Santa Maria Nuova (Reggio Emilia, Italy) between 1 January 1986 and 31 December 2001. Both hospitals are the only referral centers for populations living in central Galicia and central Emilia Romagna, respectively. During the period of study, 194 Lugo residents and 126 Reggio Emilia residents were diagnosed with biopsy proven GCA. Reggio Emilia patients were more likely to be female (74% vs 54%; p = 0.0001). Although Lugo patients complained of headache (86%) more commonly than did those from Reggio Emilia (77%), the difference was only marginally significant (p = 0.05). The proportion of patients with visual manifestations or visual loss was remarkably similar (22% for visual manifestations and 17% for visual loss in Lugo and 29% and 21% for Reggio Emilia residents). The mean erythrocyte sedimentation rate prior to the onset of therapy was also similar. Apart from differences in sex, the clinical spectrum of GCA in these 2 Southern European regions was similar.

Crystal Structures of the GCaMP Calcium Sensor Reveal the Mechanism of Fluorescence Signal Change and Aid Rational Design

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

Akerboom, Jasper; Velez Rivera, Jonathan D.; Rodriguez Guilbe, María M.

The genetically encoded calcium indicator GCaMP2 shows promise for neural network activity imaging, but is currently limited by low signal-to-noise ratio. We describe x-ray crystal structures as well as solution biophysical and spectroscopic characterization of GCaMP2 in the calcium-free dark state, and in two calcium-bound bright states: a monomeric form that dominates at intracellular concentrations observed during imaging experiments and an unexpected domain-swapped dimer with decreased fluorescence. This series of structures provides insight into the mechanism of Ca{sup 2+}-induced fluorescence change. Upon calcium binding, the calmodulin (CaM) domain wraps around the M13 peptide, creating a new domain interface between CaMmore » and the circularly permuted enhanced green fluorescent protein domain. Residues from CaM alter the chemical environment of the circularly permuted enhanced green fluorescent protein chromophore and, together with flexible inter-domain linkers, block solvent access to the chromophore. Guided by the crystal structures, we engineered a series of GCaMP2 point mutants to probe the mechanism of GCaMP2 function and characterized one mutant with significantly improved signal-to-noise. The mutation is located at a domain interface and its effect on sensor function could not have been predicted in the absence of structural data.« less

Structural analysis of retinal photoreceptor ellipsoid zone and postreceptor retinal layer associated with visual acuity in patients with retinitis pigmentosa by ganglion cell analysis combined with OCT imaging

PubMed Central

Liu, Guodong; Li, Hui; Liu, Xiaoqiang; Xu, Ding; Wang, Fang

2016-01-01

Abstract The aim of this study was to examine changes in photoreceptor ellipsoid zone (EZ) and postreceptor retinal layer in retinitis pigmentosa (RP) patients by ganglion cell analysis (GCA) combined with optical coherence tomography (OCT) imaging to evaluate the structure–function relationships between retinal layer changes and best corrected visual acuity (BCVA). Sixty-eight eyes of 35 patients with RP and 65 eyes of 35 normal controls were analyzed in the study. The average length of EZ was 911.1 ± 208.8 μm in RP patients, which was shortened with the progression of the disease on the OCT images. The average ganglion cell–inner plexiform layer thickness (GCIPLT) was 54.7 ± 18.9 μm in RP patients, while in normal controls it was 85.6 ± 6.8 μm. The GCIPLT in all quarters became significantly thinner along with outer retinal thinning. There was a significantly positive correlation between BCVA and EZ (r = −0.7622, P < 0.001) and GCIPLT (r = −0.452, P < 0.001). Therefore, we assess the retinal layer changes from a new perspective in RP patients, which suggests that EZ and GCIPLT obtained by GCA combined with OCT imaging are the direct and valid indicators to diagnosis and predict the pathological process of RP. PMID:28033301

Molecular Mechanisms of Soft Tissue Regeneration and Bone Formation in Mice: Implication in Fracture Repair and Wound Healing in Humans

DTIC Science & Technology

2008-04-01

designed in this study: Mg4718-F: 5’-GCA TTT TGA TCC CTT ATA ATA CA-3’ Mg4718-R: 5’- GTG GAA GAC CCT TGA ATG G-3’ Mg4723-F: 5’-GCA TAG CCA ACA AAA...GAA ATC TAA TG-3’ Mg4723-R: 5’-GCA GTG TAG CTC AGT GGT AGA TCA C-3’ After each cross, the progenies were genotyped as described above. We have also...mutant F2 mice. PPD is a likelihood statistic that gives rise to the 95% confidence intervals, which is indicated by gray horizontal bars. cM

CORRESPONDENCE OF STABLE ISOTOPE AND GUT CONTENTS ANALYSES IN DETERMINING TROPHIC POSITION OF STREAM FISHES

EPA Science Inventory

It is generally accepted that both stable isotope analysis (SIA) and gut contents analysis (GCA) be used in food web studies; however, few researchers have analyzed these data in concert. We utilized SIA and GCA to determine if longitudinal and seasonal variation in diet affects...

Comparing trophic position of stream fishes using stable isotope and gut contents analyses

EPA Science Inventory

Stable isotope analysis (SIA) and gut content analysis (GCA) are commonly used in food web studies, but few studies analyze these data in concert. We used SIA and GCA to identify diets and trophic position (TP) of six stream fishes and to compare TP estimates between methods. Ord...

Children's Perspectives on Conceptual Games Teaching: A Value-Adding Experience

ERIC Educational Resources Information Center

Fry, Joan Marian; Tan, Clara Wee Keat; McNeill, Michael; Wright, Steven

2010-01-01

Background: Revisions of the Singaporean physical education (PE) syllabus in 1999 and 2006 included a conceptual approach to teaching games. The games concept approach (GCA), a form of constructivist pedagogy, was a distinct departure from the direct teaching methods traditionally used in the country. Following the GCA's introduction into a PE…

Polymyalgia rheumatica and giant cell arteritis: a 5-year epidemiologic and clinical study in Reggio Emilia, Italy.

PubMed

Salvarani, C; Macchioni, P L; Tartoni, P L; Rossi, F; Baricchi, R; Castri, C; Chiaravalloti, F; Portioli, I

1987-01-01

Among the population of Reggio Emilia, Italy, 56 patients with polymyalgia rheumatica (PR) and giant cell arteritis (GCA) were identified during the 5-year period 1981-85. The average annual incidence rates of PR and GCA were 12.8 and 8.8 respectively per 100,000 population aged 50 years or older. Forty-nine patients were followed up and the mean duration of follow-up was 32 months. All the patients received steroid therapy. We have evaluated the cumulative probability of requiring continued steroid therapy between patients with PR only, GCA only, and PR associated with GCA using life-table methods with permanent discontinuation of therapy as an end point. The different duration of steroid therapy between these 3 groups did not achieve statistical significance by the method of Lee and Desu. We identified a 5 variable discriminant function that correctly predicted whether the duration of therapy would be longer or shorter than 16 months (median duration of therapy) in 80% of our patients followed up for at least 24 months. The presence of synovitis in PR is also discussed.

Sensitive red protein calcium indicators for imaging neural activity

PubMed Central

Dana, Hod; Mohar, Boaz; Sun, Yi; Narayan, Sujatha; Gordus, Andrew; Hasseman, Jeremy P; Tsegaye, Getahun; Holt, Graham T; Hu, Amy; Walpita, Deepika; Patel, Ronak; Macklin, John J; Bargmann, Cornelia I; Ahrens, Misha B; Schreiter, Eric R; Jayaraman, Vivek; Looger, Loren L; Svoboda, Karel; Kim, Douglas S

2016-01-01

Genetically encoded calcium indicators (GECIs) allow measurement of activity in large populations of neurons and in small neuronal compartments, over times of milliseconds to months. Although GFP-based GECIs are widely used for in vivo neurophysiology, GECIs with red-shifted excitation and emission spectra have advantages for in vivo imaging because of reduced scattering and absorption in tissue, and a consequent reduction in phototoxicity. However, current red GECIs are inferior to the state-of-the-art GFP-based GCaMP6 indicators for detecting and quantifying neural activity. Here we present improved red GECIs based on mRuby (jRCaMP1a, b) and mApple (jRGECO1a), with sensitivity comparable to GCaMP6. We characterized the performance of the new red GECIs in cultured neurons and in mouse, Drosophila, zebrafish and C. elegans in vivo. Red GECIs facilitate deep-tissue imaging, dual-color imaging together with GFP-based reporters, and the use of optogenetics in combination with calcium imaging. DOI: http://dx.doi.org/10.7554/eLife.12727.001 PMID:27011354

The Genetics Concept Assessment: A New Concept Inventory for Gauging Student Understanding of Genetics

ERIC Educational Resources Information Center

Smith, Michelle K.; Wood, William B.; Knight, Jennifer K.

2008-01-01

We have designed, developed, and validated a 25-question Genetics Concept Assessment (GCA) to test achievement of nine broad learning goals in majors and nonmajors undergraduate genetics courses. Written in everyday language with minimal jargon, the GCA is intended for use as a pre- and posttest to measure student learning gains. The assessment…

Piper sarmentosum is comparable to glycyrrhizic acid in reducing visceral fat deposition in adrenalectomised rats given dexamethasone.

PubMed

Fairus, A; Ima Nirwana, S; Elvy Suhana, M R; Tan, M H; Santhana, R; Farihah, H S

2013-01-01

Visceral obesity may be due to the dysregulation of cortisol production or metabolism that lead to metabolic disease. In adipose tissue, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 regulates cortisol metabolism (11beta-HSD1). A previous study showed an increase in the visceral fat deposition in adrenalectomised rats given intramuscular dexamethasone. Glycyrrhizic acid (GCA) has been shown to reduce fat deposition because it is a known potent inhibitor of the 11beta-HSD1 enzyme. Piper sarmentosum (PS) is an edible medicinal plant commonly used in Asia as traditional medicine for treating diabetes, hypertension and joint pains. In this study, we determined the effects of PS extract on the disposition and morphology of perirenal adipocytes of adrenalectomised rats given intramuscular dexamethasone. A total of 21 male Spraque Dawley rats were adrenalectomised and given intramuscular dexamethasone, 120 μg/kg/day. These rats were further divided into three groups: adrenalectomised control (ADR+Dexa; n=7), GCA-treated (ADR+Dexa+GCA; dose=240 mg/kg/day; n=7) and PS-treated (ADR+Dexa+PS; dose=125 mg/kg/day; n=7) groups. The various treatments were given via gastric gavage following 2 weeks of adrenalectomy. Treatment with PS extract for 8 weeks showed decreased deposition of perirenal adipocytes which was similar to the GCA-treated group. However, PS-treated rats had thinner adipocyte membrane compared with that of the GCA-treated group. In conclusion, PS extract decreased perirenal fat deposition and reduced the diameter of the adipocyte membrane. However, the mechanisms of action needed further study.

Simultaneous GCaMP6-based fiber photometry and fMRI in rats.

PubMed

Liang, Zhifeng; Ma, Yuncong; Watson, Glenn D R; Zhang, Nanyin

2017-09-01

Understanding the relationship between neural and vascular signals is essential for interpretation of functional MRI (fMRI) results with respect to underlying neuronal activity. Simultaneously measuring neural activity using electrophysiology with fMRI has been highly valuable in elucidating the neural basis of the blood oxygenation-level dependent (BOLD) signal. However, this approach is also technically challenging due to the electromagnetic interference that is observed in electrophysiological recordings during MRI scanning. Recording optical correlates of neural activity, such as calcium signals, avoids this issue, and has opened a new avenue to simultaneously acquire neural and BOLD signals. The present study is the first to demonstrate the feasibility of simultaneously and repeatedly acquiring calcium and BOLD signals in animals using a genetically encoded calcium indicator, GCaMP6. This approach was validated with a visual stimulation experiment, during which robust increases of both calcium and BOLD signals in the superior colliculus were observed. In addition, repeated measurement in the same animal demonstrated reproducible calcium and BOLD responses to the same stimuli. Taken together, simultaneous GCaMP6-based fiber photometry and fMRI recording presents a novel, artifact-free approach to simultaneously measuring neural and fMRI signals. Furthermore, given the cell-type specificity of GCaMP6, this approach has the potential to mechanistically dissect the contributions of individual neuron populations to BOLD signal, and ultimately reveal its underlying neural mechanisms. The current study established the method for simultaneous GCaMP6-based fiber photometry and fMRI in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Multiple Cranial Nerve Palsies in Giant Cell Arteritis.

PubMed

Ross, Michael; Bursztyn, Lulu; Superstein, Rosanne; Gans, Mark

2017-12-01

Giant cell arteritis (GCA) is a systemic vasculitis of medium and large arteries often with ophthalmic involvement, including ischemic optic neuropathy, retinal artery occlusion, and ocular motor cranial nerve palsies. This last complication occurs in 2%-15% of patients, but typically involves only 1 cranial nerve. We present 2 patients with biopsy-proven GCA associated with multiple cranial nerve palsies.

Giant cell angiofibroma misdiagnosed as a vascular malformation and treated with absolute alcohol for one year: a case report and review of the literature.

PubMed

He, Yue; Zhang, Chenping; Liu, Guanglong; Tian, Zhuowei; Wang, Lizhen; Kalfarentzos, Evagelos

2014-04-24

To present the clinical, imaging, pathological and immunohistochemical features of giant cell angiofibroma (GCA). In this paper we report an atypical case of a GCA extending from the parotid to the parapharyngeal space. The lesion was being treated as a vascular malformation for one year prior to surgical removal. We summarize the clinical manifestations, imaging, pathological and molecular features of this rare disease.After complete surgical removal of the tumor, immunohistochemical analysis revealed strong positivity for the mesenchymal markers vimentin, CD34, CD31 and CD99 in neoplastic cells. Tumor proliferation antigen marker Ki67 was partly positive (<5% of cells). Tumor cells were negative for muscle-specific actin, epithelial membrane antigen, smooth muscle actin, cytokeratin pan, S100, desmin, glial fibrillary acidic protein, myogenin, MyoD1 and F8. The morphological and immunohistochemical profile was consistent with the diagnosis of GCA. GCA is a rare soft tissue tumor that can easily be misdiagnosed in the clinical preoperative setting. In view of the clinical, pathological and molecular features of the tumor, complete surgical removal is the current optimal treatment option, providing accurate diagnosis and low to minimal recurrence rate.

Evaluation results for the positive deep-UV resist AZ DX 46

NASA Astrophysics Data System (ADS)

Spiess, Walter; Lynch, Thomas J.; Le Cornec, Charles; Escher, Gary C.; Kinoshita, Yoshiaki; Kochan, John; Kudo, Takanori; Masuda, Seiya; Mourier, Thierry; Nozaki, Yuko; Olson, Setha G.; Okazaki, Hiroshi; Padmanaban, Munirathna; Pawlowski, Georg; Przybilla, Klaus J.; Roeschert, Horst; Suehiro, Natusmi; Vinet, Francoise; Wengenroth, Horst

1994-05-01

This contribution emphasizes resist application site by communicating lithographic results for AZ DX 46, obtained using the GCA XLS 7800/31 stepper, NA equals 0.53, equipped with krypton fluoride excimer laser ((lambda) equals 248 nm), model 4500 D, as exposure source, delivered by Cymer Laser Technologies. As far as delay time experiments are concerned ASM-L PAS 5500/70 stepper, NA equals 0.42, was used in combination with Lambda Physik excimer laser, model 248 L.

How Do You Do What You Do? Examining the Development of Quality Teaching in Using GCA in PETE Teachers

ERIC Educational Resources Information Center

Forrest, Gregory John; Wright, Jan; Pearson, Phil

2012-01-01

Background: The move for educational reform to improve student outcomes and learning has been the subject of ongoing debate over the last 15 years in Australia and internationally. In Australia, Game Centred Approaches (GCA) such as Game Sense have been positioned by advocates as having the capacity to achieve these characteristics in physical…

Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons.

PubMed

Ma, Ying; Shaik, Mohammed A; Kozberg, Mariel G; Kim, Sharon H; Portes, Jacob P; Timerman, Dmitriy; Hillman, Elizabeth M C

2016-12-27

Brain hemodynamics serve as a proxy for neural activity in a range of noninvasive neuroimaging techniques including functional magnetic resonance imaging (fMRI). In resting-state fMRI, hemodynamic fluctuations have been found to exhibit patterns of bilateral synchrony, with correlated regions inferred to have functional connectivity. However, the relationship between resting-state hemodynamics and underlying neural activity has not been well established, making the neural underpinnings of functional connectivity networks unclear. In this study, neural activity and hemodynamics were recorded simultaneously over the bilateral cortex of awake and anesthetized Thy1-GCaMP mice using wide-field optical mapping. Neural activity was visualized via selective expression of the calcium-sensitive fluorophore GCaMP in layer 2/3 and 5 excitatory neurons. Characteristic patterns of resting-state hemodynamics were accompanied by more rapidly changing bilateral patterns of resting-state neural activity. Spatiotemporal hemodynamics could be modeled by convolving this neural activity with hemodynamic response functions derived through both deconvolution and gamma-variate fitting. Simultaneous imaging and electrophysiology confirmed that Thy1-GCaMP signals are well-predicted by multiunit activity. Neurovascular coupling between resting-state neural activity and hemodynamics was robust and fast in awake animals, whereas coupling in urethane-anesthetized animals was slower, and in some cases included lower-frequency (<0.04 Hz) hemodynamic fluctuations that were not well-predicted by local Thy1-GCaMP recordings. These results support that resting-state hemodynamics in the awake and anesthetized brain are coupled to underlying patterns of excitatory neural activity. The patterns of bilaterally-symmetric spontaneous neural activity revealed by wide-field Thy1-GCaMP imaging may depict the neural foundation of functional connectivity networks detected in resting-state fMRI.

Resting-state hemodynamics are spatiotemporally coupled to synchronized and symmetric neural activity in excitatory neurons

PubMed Central

Ma, Ying; Shaik, Mohammed A.; Kozberg, Mariel G.; Portes, Jacob P.; Timerman, Dmitriy

2016-01-01

Brain hemodynamics serve as a proxy for neural activity in a range of noninvasive neuroimaging techniques including functional magnetic resonance imaging (fMRI). In resting-state fMRI, hemodynamic fluctuations have been found to exhibit patterns of bilateral synchrony, with correlated regions inferred to have functional connectivity. However, the relationship between resting-state hemodynamics and underlying neural activity has not been well established, making the neural underpinnings of functional connectivity networks unclear. In this study, neural activity and hemodynamics were recorded simultaneously over the bilateral cortex of awake and anesthetized Thy1-GCaMP mice using wide-field optical mapping. Neural activity was visualized via selective expression of the calcium-sensitive fluorophore GCaMP in layer 2/3 and 5 excitatory neurons. Characteristic patterns of resting-state hemodynamics were accompanied by more rapidly changing bilateral patterns of resting-state neural activity. Spatiotemporal hemodynamics could be modeled by convolving this neural activity with hemodynamic response functions derived through both deconvolution and gamma-variate fitting. Simultaneous imaging and electrophysiology confirmed that Thy1-GCaMP signals are well-predicted by multiunit activity. Neurovascular coupling between resting-state neural activity and hemodynamics was robust and fast in awake animals, whereas coupling in urethane-anesthetized animals was slower, and in some cases included lower-frequency (<0.04 Hz) hemodynamic fluctuations that were not well-predicted by local Thy1-GCaMP recordings. These results support that resting-state hemodynamics in the awake and anesthetized brain are coupled to underlying patterns of excitatory neural activity. The patterns of bilaterally-symmetric spontaneous neural activity revealed by wide-field Thy1-GCaMP imaging may depict the neural foundation of functional connectivity networks detected in resting-state fMRI. PMID:27974609

Optical dissection of odor information processing in vivo using GCaMPs expressed in specified cell types of the olfactory bulb

PubMed Central

Wachowiak, Matt; Economo, Michael N.; Díaz-Quesada, Marta; Brunert, Daniela; Wesson, Daniel W.; White, John. A.; Rothermel, Markus

2013-01-01

Understanding central processing requires precise monitoring of neural activity across populations of identified neurons in the intact brain. Here we used recently-optimized variants of the genetically-encoded calcium sensor GCaMP (GCaMP3 and GCaMPG5G) to image activity among genetically- and anatomically-defined neuronal populations in the olfactory bulb (OB), including two types of GABA-ergic interneurons (periglomerular (PG) and short axon (SA) cells) and OB output neurons (mitral/tufted (MT) cells) projecting to piriform cortex. We first established that changes in neuronal spiking can be accurately related to GCaMP fluorescence changes via a simple quantitative relationship over a large dynamic range. We next used in vivo two-photon imaging from individual neurons and epifluorescence signals reflecting population-level activity to investigate the spatiotemporal representation of odorants across these neuron types in anesthetized and awake mice. Under anesthesia, individual PG and SA cells showed temporally simple responses and little spontaneous activity, while MT cells were spontaneously active and showed diverse temporal responses. At the population level, response patterns of PG, SA and MT cells were surprisingly similar to those imaged from sensory inputs, with shared odorant-specific topography across the dorsal OB and inhalation-coupled temporal dynamics. During wakefulness, PG and SA cell responses increased in magnitude but remained temporally simple while those of MT cells changed to complex spatiotemporal patterns reflecting restricted excitation and widespread inhibition. These results point to multiple circuit elements with distinct roles in transforming odor representations in the OB and provide a framework for further dissecting early olfactory processing using optical and genetic tools. PMID:23516293

Vascular endothelial growth factor levels and rheumatic diseases of the elderly.

PubMed

Smets, Perrine; Devauchelle-Pensec, Valérie; Rouzaire, Paul-Olivier; Pereira, Bruno; Andre, Marc; Soubrier, Martin

2016-12-01

Increasing vascular endothelial growth factor (VEGF) has been reported in remitting symmetrical seronegative synovitis with pitting edema (RS3PE) syndrome, rheumatoid arthritis (RA), polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). The aim of this study was to compare VEGF levels in patients over 60 years of age who have RS3PE, RA, PMR or GCA so as to determine whether elevated VEGF is specific for a rheumatic disease, the inflammation or edema that occurs with these pathological conditions. In this retrospective, multicentric study we assessed serum and plasma levels of VEGF in patients over 60 years of age with rheumatic diseases that were either de novo or of recent onset according to the initial clinical presentation, and we compared these patients with a control group. Serum and plasma VEGF levels were determined in 80 patients (5 with RS3PE, 13 with RA, 44 with PMR, and 18 with GCA) and 37 controls. Edema occurred in five patients with RS3PE, four with RA, and one with PMR, but not patients with GCA. Serum VEGF levels were significantly higher in individuals with rheumatic diseases (849 (405.5-1235.5) pg/ml) relative to the controls (484 (302-555) pg/ml) (p < 0.001). There were no significant differences between patients with RS3PE, RA, PMR, or GCA in terms of the VEGF serum levels (p = 0.60) or plasma levels (p = 0.57). Similarly, the occurrence of edema did not correlate with VEGF levels. VEGF increases in rheumatic diseases compared to a control group. This was not associated with specific rheumatic diseases or with edematous rheumatic diseases.

Pilot Production of Large Area Microchannel Plates and Picosecond Photodetectors

NASA Astrophysics Data System (ADS)

Minot, M.; Adams, B.; Abiles, M.; Bond, J.; Craven, C.; Cremer, T.; Foley, M.; Lyashenko, A.; Popecki, M.; Stochaj, M.; Worstell, W.; Elam, J.; Mane, A.; Siegmund, O.; Ertley, C.

2016-09-01

Pilot production performance is reported for large area atomic layer deposition (ALD) coated microchannel plates (ALD-GCA-MCPs) and for Large Area Picosecond Photodetectors (LAPPD™) which incorporate them. "Hollowcore" glass capillary array (GCA) substrates are coated with ALD resistive and emissive layers to form the ALDGCA- MCPs, an approach that facilitates independent selection of glass substrates that are mechanically stronger and that have lower levels of radioactive alkali elements compared to conventional MCP lead glass, reducing background noise[1,2,3,4]. ALD-GCA-MCPs have competitive gain ( 104 each or 107 for a chevron pair ), enhanced lifetime and gain stability (7 C cm-2 of charge extraction), reduced background levels (0.028 events cm-2 sec-1) and low gamma-ray detection efficiency. They can be fabricated in large area (20cm X 20 cm) planar and curved formats suitable for use in high radiation environment applications, including astronomy, space instrumentation, and remote night time sensing. The LAPPD™ photodetector incorporates these ALD-GCA-MCPs in an all-glass hermetic package with top and bottom plates and sidewalls made of borosilicate float glass. Signals are generated by a bi-alkali Na2KSb photocathode, amplified with a stacked chevron pair of ALD-GCA-MCPs. Signals are collected on RF strip-line anodes integrated into to the bottom plates which exit the detector via pin-free hermetic seals under the side walls [5]. Tests show that LAPPDTMs have electron gains greater than 107, submillimeter spatial resolution for large (multiphoton) pulses and several mm for single photons, time resolution less than 50 picoseconds for single photons, predicted resolution less than 5 picoseconds for large pulses, high stability versus charge extraction[6], and good uniformity for applications including astrophysics, neutron detection, high energy physics Cherenkov light detection, and quantum-optical photon-correlation experiments.

Extensive Karyotype Reorganization in the Fish Gymnotus arapaima (Gymnotiformes, Gymnotidae) Highlighted by Zoo-FISH Analysis.

PubMed

Machado, Milla de Andrade; Pieczarka, Julio C; Silva, Fernando H R; O'Brien, Patricia C M; Ferguson-Smith, Malcolm A; Nagamachi, Cleusa Y

2018-01-01

The genus Gymnotus (Gymnotiformes) contains over 40 species of freshwater electric fishes exhibiting a wide distribution throughout Central and South America, and being particularly prevalent in the Amazon basin. Cytogenetics has been an important tool in the cytotaxonomy and elucidation of evolutionary processes in this genus, including the unraveling the variety of diploid chromosome number (2 n = from 34 to 54), the high karyotype diversity among species with a shared diploid number, different sex chromosome systems, and variation in the distribution of several Repetitive DNAs and colocation and association between those sequences. Recently whole chromosome painting (WCP) has been used for tracking the chromosomal evolution of the genus, showing highly reorganized karyotypes and the conserved synteny of the NOR bearing par within the clade G. carapo . In this study, painting probes derived from the chromosomes of G. carapo (GCA, 2 n = 42, 30 m/sm + 12 st/a) were hybridized to the mitotic metaphases of G. arapaima (GAR, 2 n = 44, 24 m/sm + 20 st/a). Our results uncovered chromosomal rearrangements and a high number of repetitive DNA regions. From the 12 chromosome pairs of G. carapo that can be individually differentiated (GCA1-3, 6, 7, 9, 14, 16, and 18-21), six pairs (GCA 1, 9, 14, 18, 20, 21) show conserved homology with GAR, five pairs (GCA 1, 9, 14, 20, 21) are also shared with cryptic species G. carapo 2 n = 40 (34 m/sm + 6 st/a) and only the NOR bearing pair (GCA 20) is shared with G. capanema (GCP 2 n = 34, 20 m/sm + 14 st/a). The remaining chromosomes are reorganized in the karyotype of GAR. Despite the close phylogenetic relationships of these species, our chromosome painting studies demonstrate an extensive reorganization of their karyotypes.

Natriuretic peptides buffer renin-dependent hypertension.

PubMed

Demerath, Theo; Staffel, Janina; Schreiber, Andrea; Valletta, Daniela; Schweda, Frank

2014-06-15

The renin-angiotensin-aldosterone system and cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are opposing control mechanisms for arterial blood pressure. Accordingly, an inverse relationship between plasma renin concentration (PRC) and ANP exists in most circumstances. However, PRC and ANP levels are both elevated in renovascular hypertension. Because ANP can directly suppress renin release, we used ANP knockout (ANP(-/-)) mice to investigate whether high ANP levels attenuate the increase in PRC in response to renal hypoperfusion, thus buffering renovascular hypertension. ANP(-/-) mice were hypertensive and had reduced PRC compared with that in wild-type ANP(+/+) mice under control conditions. Unilateral renal artery stenosis (2-kidney, 1-clip) for 1 wk induced similar increases in blood pressure and PRC in both genotypes. Unexpectedly, plasma BNP concentrations in ANP(-/-) mice significantly increased in response to two-kidney, one-clip treatment, potentially compensating for the lack of ANP. In fact, in mice lacking guanylyl cyclase A (GC-A(-/-) mice), which is the common receptor for both ANP and BNP, renovascular hypertension was markedly augmented compared with that in wild-type GC-A(+/+) mice. However, the higher blood pressure in GC-A(-/-) mice was not caused by disinhibition of the renin system because PRC and renal renin synthesis were significantly lower in GC-A(-/-) mice than in GC-A(+/+) mice. Thus, natriuretic peptides buffer renal vascular hypertension via renin-independent effects, such as vasorelaxation. The latter possibility is supported by experiments in isolated perfused mouse kidneys, in which physiological concentrations of ANP and BNP elicited renal vasodilatation and attenuated renal vasoconstriction in response to angiotensin II. Copyright © 2014 the American Physiological Society.

Genetic effects and genotype × environment interactions govern seed oil content in Brassica napus L.

PubMed

Guo, Yanli; Si, Ping; Wang, Nan; Wen, Jing; Yi, Bin; Ma, Chaozhi; Tu, Jinxing; Zou, Jitao; Fu, Tingdong; Shen, Jinxiong

2017-01-05

As seed oil content (OC) is a key measure of rapeseed quality, better understanding the genetic basis of OC would greatly facilitate the breeding of high-oil cultivars. Here, we investigated the components of genetic effects and genotype × environment interactions (GE) that govern OC using a full diallel set of nine parents, which represented a wide range of the Chinese rapeseed cultivars and pure lines with various OCs. Our results from an embryo-cytoplasm-maternal (GoCGm) model for diploid seeds showed that OC was primarily determined by genetic effects (V G ) and GE (V GE ), which together accounted for 86.19% of the phenotypic variance (V P ). GE (V GE ) alone accounted for 51.68% of the total genetic variance, indicating the importance of GE interaction for OC. Furthermore, maternal variance explained 75.03% of the total genetic variance, embryo and cytoplasmic effects accounted for 21.02% and 3.95%, respectively. We also found that the OC of F 1 seeds was mainly determined by maternal effect and slightly affected by xenia. Thus, the OC of rapeseed was simultaneously affected by various genetic components, including maternal, embryo, cytoplasm, xenia and GE effects. In addition, general combining ability (GCA), specific combining ability (SCA), and maternal variance had significant influence on OC. The lines H2 and H1 were good general combiners, suggesting that they would be the best parental candidates for OC improvement. Crosses H3 × M2 and H1 × M3 exhibited significant SCA, suggesting their potentials in hybrid development. Our study thoroughly investigated and reliably quantified various genetic factors associated with OC of rapeseed by using a full diallel and backcross and reciprocal backcross. This findings lay a foundation for future genetic studies of OC and provide guidance for breeding of high-oil rapeseed cultivars.

Giant cell angiofibroma misdiagnosed as a vascular malformation and treated with absolute alcohol for one year: a case report and review of the literature

PubMed Central

2014-01-01

Purpose To present the clinical, imaging, pathological and immunohistochemical features of giant cell angiofibroma (GCA). Case presentation In this paper we report an atypical case of a GCA extending from the parotid to the parapharyngeal space. The lesion was being treated as a vascular malformation for one year prior to surgical removal. We summarize the clinical manifestations, imaging, pathological and molecular features of this rare disease. After complete surgical removal of the tumor, immunohistochemical analysis revealed strong positivity for the mesenchymal markers vimentin, CD34, CD31 and CD99 in neoplastic cells. Tumor proliferation antigen marker Ki67 was partly positive (<5% of cells). Tumor cells were negative for muscle-specific actin, epithelial membrane antigen, smooth muscle actin, cytokeratin pan, S100, desmin, glial fibrillary acidic protein, myogenin, MyoD1 and F8. The morphological and immunohistochemical profile was consistent with the diagnosis of GCA. Conclusion GCA is a rare soft tissue tumor that can easily be misdiagnosed in the clinical preoperative setting. In view of the clinical, pathological and molecular features of the tumor, complete surgical removal is the current optimal treatment option, providing accurate diagnosis and low to minimal recurrence rate. PMID:24758544

Electrical Neural Stimulation and Simultaneous in Vivo Monitoring with Transparent Graphene Electrode Arrays Implanted in GCaMP6f Mice.

PubMed

Park, Dong-Wook; Ness, Jared P; Brodnick, Sarah K; Esquibel, Corinne; Novello, Joseph; Atry, Farid; Baek, Dong-Hyun; Kim, Hyungsoo; Bong, Jihye; Swanson, Kyle I; Suminski, Aaron J; Otto, Kevin J; Pashaie, Ramin; Williams, Justin C; Ma, Zhenqiang

2018-01-23

Electrical stimulation using implantable electrodes is widely used to treat various neuronal disorders such as Parkinson's disease and epilepsy and is a widely used research tool in neuroscience studies. However, to date, devices that help better understand the mechanisms of electrical stimulation in neural tissues have been limited to opaque neural electrodes. Imaging spatiotemporal neural responses to electrical stimulation with minimal artifact could allow for various studies that are impossible with existing opaque electrodes. Here, we demonstrate electrical brain stimulation and simultaneous optical monitoring of the underlying neural tissues using carbon-based, fully transparent graphene electrodes implanted in GCaMP6f mice. Fluorescence imaging of neural activity for varying electrical stimulation parameters was conducted with minimal image artifact through transparent graphene electrodes. In addition, full-field imaging of electrical stimulation verified more efficient neural activation with cathode leading stimulation compared to anode leading stimulation. We have characterized the charge density limitation of capacitive four-layer graphene electrodes as 116.07-174.10 μC/cm 2 based on electrochemical impedance spectroscopy, cyclic voltammetry, failure bench testing, and in vivo testing. This study demonstrates the transparent ability of graphene neural electrodes and provides a method to further increase understanding and potentially improve therapeutic electrical stimulation in the central and peripheral nervous systems.

Socioeconomic status, child enrichment factors, and cognitive performance among preschool-age children: results from the Follow-Up of Growth and Development Experiences study.

PubMed

Christensen, Deborah L; Schieve, Laura A; Devine, Owen; Drews-Botsch, Carolyn

2014-07-01

Lower cognitive performance is associated with poorer health and functioning throughout the lifespan and disproportionately affects children from lower socioeconomic status (SES) populations. Previous studies reporting positive associations between child home enrichment and cognitive performance generally had a limited distribution of SES. We evaluated the associations of SES and child enrichment with cognitive performance in a population with a wide range of SES, particularly whether enrichment attenuates associations with SES. Children were sampled from a case-control study of small-for-gestational-age (SGA) conducted in a public hospital serving a low SES population (final n=198) and a private hospital serving a middle-to-high SES population (final n=253). SES (maternal education and income) and perinatal factors (SGA, maternal smoking and drinking) were obtained from maternal birth interview. Five child home enrichment factors (e.g. books in home) and preschool attendance were obtained from follow-up interview at age 4.5 years. Cognitive performance was assessed with the Differential Ability Scales (DAS), a standardized psychometric test administered at follow-up. SES and enrichment scores were created by combining individual factors. Analyses were adjusted for perinatal factors. Children from the public birth hospital had a significantly lower mean DAS general cognitive ability (GCA) score than children born at the private birth hospital (adjusted mean difference -21.4, 95% CI: -24.0, -18.7); this was substantially attenuated by adjustment for individual SES, child enrichment factors, and preschool attendance (adjusted mean difference -5.1, 95% CI: -9.5, -0.7). Individual-level SES score was associated with DAS score, beyond the general SES effect associated with hospital of birth. Adjustment for preschool attendance and home enrichment score attenuated the association between individual SES score and adjusted mean DAS-GCA among children born at both of the hospitals. The effect of being in the lower compared to the middle tertile of SES score was reduced by approximately a quarter; the effect of being in the upper compared to the middle tertile of SES score was reduced by nearly half, but this comparison was possible only for children born at the private hospital. A child's individual SES was associated with cognitive performance within advantaged and disadvantaged populations. Child enrichment was associated with better cognitive performance and attenuated the SES influence. Health care providers should reinforce guidelines for home enrichment and refer children with delays to early intervention and education, particularly children from disadvantaged populations. Copyright © 2014. Published by Elsevier Ltd.

The Effects of System and Environmental Factors Upon Experienced Pilot Performance in the Advanced Simulator for Pilot Training

DTIC Science & Technology

1977-04-01

System by System Variable Interactions Across All Maneuvers ... .......... 23 11 Field of View by Motion Interaction Cell Means for Takeoff...23 12 Motion by Field :f View Interaction Cell Means for GCA ..... ................. 24 13 Motion by FOV Interaction Mc--n Ratings for the...GCA and Takeoff Maneuvers ... ....... 24 14 Motion by G.Seat Interaction Cell Means for Takeoff ...... ................... 25 15 Motion by G.Seat

Stem Cell-Based Therapies for Epidermolysis Bullosa

DTIC Science & Technology

2015-12-01

GTG  GCT  CAG   GTG  GCC  AGT...ATC  CGA  GCA  GTT  CTC  AGC  AGT  CCT  GCA   GTG  ACA  GAG  CAG  GAG   GTG  GCT  CAG   GTG  GCC  AGT  GCC... GTG  (still  valine)   12   Cell  Sorting   Representative  example  shown.  Note  significant  transfection

Diagnostic classification of macular ganglion cell and retinal nerve fiber layer analysis: differentiation of false-positives from glaucoma.

PubMed

Kim, Ko Eun; Jeoung, Jin Wook; Park, Ki Ho; Kim, Dong Myung; Kim, Seok Hwan

2015-03-01

To investigate the rate and associated factors of false-positive diagnostic classification of ganglion cell analysis (GCA) and retinal nerve fiber layer (RNFL) maps, and characteristic false-positive patterns on optical coherence tomography (OCT) deviation maps. Prospective, cross-sectional study. A total of 104 healthy eyes of 104 normal participants. All participants underwent peripapillary and macular spectral-domain (Cirrus-HD, Carl Zeiss Meditec Inc, Dublin, CA) OCT scans. False-positive diagnostic classification was defined as yellow or red color-coded areas for GCA and RNFL maps. Univariate and multivariate logistic regression analyses were used to determine associated factors. Eyes with abnormal OCT deviation maps were categorized on the basis of the shape and location of abnormal color-coded area. Differences in clinical characteristics among the subgroups were compared. (1) The rate and associated factors of false-positive OCT maps; (2) patterns of false-positive, color-coded areas on the GCA deviation map and associated clinical characteristics. Of the 104 healthy eyes, 42 (40.4%) and 32 (30.8%) showed abnormal diagnostic classifications on any of the GCA and RNFL maps, respectively. Multivariate analysis revealed that false-positive GCA diagnostic classification was associated with longer axial length and larger fovea-disc angle, whereas longer axial length and smaller disc area were associated with abnormal RNFL maps. Eyes with abnormal GCA deviation map were categorized as group A (donut-shaped round area around the inner annulus), group B (island-like isolated area), and group C (diffuse, circular area with an irregular inner margin in either). The axial length showed a significant increasing trend from group A to C (P=0.001), and likewise, the refractive error was more myopic in group C than in groups A (P=0.015) and B (P=0.014). Group C had thinner average ganglion cell-inner plexiform layer thickness compared with other groups (group A=B>C, P=0.004). Abnormal OCT diagnostic classification should be interpreted with caution, especially in eyes with long axial lengths, large fovea-disc angles, and small optic discs. Our findings suggest that the characteristic patterns of OCT deviation map can provide useful clues to distinguish glaucomatous changes from false-positive findings. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Giant cell arteritis: diagnostic accuracy of MR imaging of superficial cranial arteries in initial diagnosis-results from a multicenter trial.

PubMed

Klink, Thorsten; Geiger, Julia; Both, Marcus; Ness, Thomas; Heinzelmann, Sonja; Reinhard, Matthias; Holl-Ulrich, Konstanze; Duwendag, Dirk; Vaith, Peter; Bley, Thorsten Alexander

2014-12-01

To assess the diagnostic accuracy of contrast material-enhanced magnetic resonance (MR) imaging of superficial cranial arteries in the initial diagnosis of giant cell arteritis ( GCA giant cell arteritis ). Following institutional review board approval and informed consent, 185 patients suspected of having GCA giant cell arteritis were included in a prospective three-university medical center trial. GCA giant cell arteritis was diagnosed or excluded clinically in all patients (reference standard [final clinical diagnosis]). In 53.0% of patients (98 of 185), temporal artery biopsy ( TAB temporal artery biopsy ) was performed (diagnostic standard [ TAB temporal artery biopsy ]). Two observers independently evaluated contrast-enhanced T1-weighted MR images of superficial cranial arteries by using a four-point scale. Diagnostic accuracy, involvement pattern, and systemic corticosteroid ( sCS systemic corticosteroid ) therapy effects were assessed in comparison with the reference standard (total study cohort) and separately in comparison with the diagnostic standard TAB temporal artery biopsy ( TAB temporal artery biopsy subcohort). Statistical analysis included diagnostic accuracy parameters, interobserver agreement, and receiver operating characteristic analysis. Sensitivity of MR imaging was 78.4% and specificity was 90.4% for the total study cohort, and sensitivity was 88.7% and specificity was 75.0% for the TAB temporal artery biopsy subcohort (first observer). Diagnostic accuracy was comparable for both observers, with good interobserver agreement ( TAB temporal artery biopsy subcohort, κ = 0.718; total study cohort, κ = 0.676). MR imaging scores were significantly higher in patients with GCA giant cell arteritis -positive results than in patients with GCA giant cell arteritis -negative results ( TAB temporal artery biopsy subcohort and total study cohort, P < .001). Diagnostic accuracy of MR imaging was high in patients without and with sCS systemic corticosteroid therapy for 5 days or fewer (area under the curve, ≥0.9) and was decreased in patients receiving sCS systemic corticosteroid therapy for 6-14 days. In 56.5% of patients with TAB temporal artery biopsy -positive results (35 of 62), MR imaging displayed symmetrical and simultaneous inflammation of arterial segments. MR imaging of superficial cranial arteries is accurate in the initial diagnosis of GCA giant cell arteritis . Sensitivity probably decreases after more than 5 days of sCS systemic corticosteroid therapy; thus, imaging should not be delayed. Clinical trial registration no. DRKS00000594 . © RSNA, 2014.

A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis.

PubMed

Carmona, F David; Vaglio, Augusto; Mackie, Sarah L; Hernández-Rodríguez, José; Monach, Paul A; Castañeda, Santos; Solans, Roser; Morado, Inmaculada C; Narváez, Javier; Ramentol-Sintas, Marc; Pease, Colin T; Dasgupta, Bhaskar; Watts, Richard; Khalidi, Nader; Langford, Carol A; Ytterberg, Steven; Boiardi, Luigi; Beretta, Lorenzo; Govoni, Marcello; Emmi, Giacomo; Bonatti, Francesco; Cimmino, Marco A; Witte, Torsten; Neumann, Thomas; Holle, Julia; Schönau, Verena; Sailler, Laurent; Papo, Thomas; Haroche, Julien; Mahr, Alfred; Mouthon, Luc; Molberg, Øyvind; Diamantopoulos, Andreas P; Voskuyl, Alexandre; Brouwer, Elisabeth; Daikeler, Thomas; Berger, Christoph T; Molloy, Eamonn S; O'Neill, Lorraine; Blockmans, Daniel; Lie, Benedicte A; Mclaren, Paul; Vyse, Timothy J; Wijmenga, Cisca; Allanore, Yannick; Koeleman, Bobby P C; Barrett, Jennifer H; Cid, María C; Salvarani, Carlo; Merkel, Peter A; Morgan, Ann W; González-Gay, Miguel A; Martín, Javier

2017-01-05

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 × 10 -54 , per-allele OR = 1.79; and rs9275592, p = 1.14 × 10 -40 , OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, p = 1.23 × 10 -10 , OR = 1.28; and rs128738, p = 4.60 × 10 -9 , OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Fast track pathway reduces sight loss in giant cell arteritis: results of a longitudinal observational cohort study.

PubMed

Patil, P; Williams, M; Maw, W W; Achilleos, K; Elsideeg, S; Dejaco, C; Borg, F; Gupta, S; Dasgupta, B

2015-01-01

To investigate the effectiveness of a fast track pathway (FTP) on sight loss in patients with suspected giant cell arteritis (GCA). A longitudinal observational cohort study was conducted in the secondary care rheumatology department. One hundred and thirty-five newly referred suspected GCA patients seen via the FTP (Jan. 2012-Dec. 2013) were compared to 81 patients seen through the conventional referral and review system (Jan. 2009-Dec. 2011). The FTP resulted in significant reduction in irreversible sight loss from 37.0% (as seen in the historical cohort 2009-2011) to 9.0 % (2012-2013, OR 0.17, p=0.001). Adjustment for clinical and demographic parameters including known risk factors for GCA associated blindness did not significantly change the primary result (OR 0.08, p=0.001). FTP resulted in a reduction of time from symptom onset to diagnosis, particularly by reduction of time from general practitioner's (GP) referral to the rheumatology review (79% of FTP patients were seen within one working day compared to 64.6 % in the conventional pathway, p=0.023). The FTP has seen a reduction in number of GP appointments. There was a significant reduction of permanent sight loss with a fast track GCA pathway. The effect may be due to multiple factors including better GP education and reduction in delayed diagnosis. These results need verification at other sites.

Concentration Addition, Independent Action and Generalized Concentration Addition Models for Mixture Effect Prediction of Sex Hormone Synthesis In Vitro

PubMed Central

Hadrup, Niels; Taxvig, Camilla; Pedersen, Mikael; Nellemann, Christine; Hass, Ulla; Vinggaard, Anne Marie

2013-01-01

Humans are concomitantly exposed to numerous chemicals. An infinite number of combinations and doses thereof can be imagined. For toxicological risk assessment the mathematical prediction of mixture effects, using knowledge on single chemicals, is therefore desirable. We investigated pros and cons of the concentration addition (CA), independent action (IA) and generalized concentration addition (GCA) models. First we measured effects of single chemicals and mixtures thereof on steroid synthesis in H295R cells. Then single chemical data were applied to the models; predictions of mixture effects were calculated and compared to the experimental mixture data. Mixture 1 contained environmental chemicals adjusted in ratio according to human exposure levels. Mixture 2 was a potency adjusted mixture containing five pesticides. Prediction of testosterone effects coincided with the experimental Mixture 1 data. In contrast, antagonism was observed for effects of Mixture 2 on this hormone. The mixtures contained chemicals exerting only limited maximal effects. This hampered prediction by the CA and IA models, whereas the GCA model could be used to predict a full dose response curve. Regarding effects on progesterone and estradiol, some chemicals were having stimulatory effects whereas others had inhibitory effects. The three models were not applicable in this situation and no predictions could be performed. Finally, the expected contributions of single chemicals to the mixture effects were calculated. Prochloraz was the predominant but not sole driver of the mixtures, suggesting that one chemical alone was not responsible for the mixture effects. In conclusion, the GCA model seemed to be superior to the CA and IA models for the prediction of testosterone effects. A situation with chemicals exerting opposing effects, for which the models could not be applied, was identified. In addition, the data indicate that in non-potency adjusted mixtures the effects cannot always be accounted for by single chemicals. PMID:23990906

A large-scale genetic analysis reveals a strong contribution of the HLA class II region to giant cell arteritis susceptibility.

PubMed

Carmona, F David; Mackie, Sarah L; Martín, Jose-Ezequiel; Taylor, John C; Vaglio, Augusto; Eyre, Stephen; Bossini-Castillo, Lara; Castañeda, Santos; Cid, Maria C; Hernández-Rodríguez, José; Prieto-González, Sergio; Solans, Roser; Ramentol-Sintas, Marc; González-Escribano, M Francisca; Ortiz-Fernández, Lourdes; Morado, Inmaculada C; Narváez, Javier; Miranda-Filloy, José A; Beretta, Lorenzo; Lunardi, Claudio; Cimmino, Marco A; Gianfreda, Davide; Santilli, Daniele; Ramirez, Giuseppe A; Soriano, Alessandra; Muratore, Francesco; Pazzola, Giulia; Addimanda, Olga; Wijmenga, Cisca; Witte, Torsten; Schirmer, Jan H; Moosig, Frank; Schönau, Verena; Franke, Andre; Palm, Øyvind; Molberg, Øyvind; Diamantopoulos, Andreas P; Carette, Simon; Cuthbertson, David; Forbess, Lindsy J; Hoffman, Gary S; Khalidi, Nader A; Koening, Curry L; Langford, Carol A; McAlear, Carol A; Moreland, Larry; Monach, Paul A; Pagnoux, Christian; Seo, Philip; Spiera, Robert; Sreih, Antoine G; Warrington, Kenneth J; Ytterberg, Steven R; Gregersen, Peter K; Pease, Colin T; Gough, Andrew; Green, Michael; Hordon, Lesley; Jarrett, Stephen; Watts, Richard; Levy, Sarah; Patel, Yusuf; Kamath, Sanjeet; Dasgupta, Bhaskar; Worthington, Jane; Koeleman, Bobby P C; de Bakker, Paul I W; Barrett, Jennifer H; Salvarani, Carlo; Merkel, Peter A; González-Gay, Miguel A; Morgan, Ann W; Martín, Javier

2015-04-02

We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10(-40), OR = 1.73). A multivariate model including class II amino acids of HLA-DRβ1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1(∗)04. An omnibus test on polymorphic amino acid positions highlighted DRβ1 13 (p = 4.08 × 10(-43)) and HLA-DQα1 47 (p = 4.02 × 10(-46)), 56, and 76 (both p = 1.84 × 10(-45)) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10(-6), OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10(-6), OR = 1.20), and REL (rs115674477, p = 1.10 × 10(-5), OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

A Large-Scale Genetic Analysis Reveals a Strong Contribution of the HLA Class II Region to Giant Cell Arteritis Susceptibility

PubMed Central

Carmona, F. David; Mackie, Sarah L.; Martín, Jose-Ezequiel; Taylor, John C.; Vaglio, Augusto; Eyre, Stephen; Bossini-Castillo, Lara; Castañeda, Santos; Cid, Maria C.; Hernández-Rodríguez, José; Prieto-González, Sergio; Solans, Roser; Ramentol-Sintas, Marc; González-Escribano, M. Francisca; Ortiz-Fernández, Lourdes; Morado, Inmaculada C.; Narváez, Javier; Miranda-Filloy, José A.; Martínez-Berriochoa, Agustín; Unzurrunzaga, Ainhoa; Hidalgo-Conde, Ana; Madroñero-Vuelta, Ana B.; Fernández-Nebro, Antonio; Ordóñez-Cañizares, M. Carmen; Escalante, Begoña; Marí-Alfonso, Begoña; Sopeña, Bernardo; Magro, César; Raya, Enrique; Grau, Elena; Román, José A.; de Miguel, Eugenio; López-Longo, F. Javier; Martínez, Lina; Gómez-Vaquero, Carmen; Fernández-Gutiérrez, Benjamín; Rodríguez-Rodríguez, Luis; Díaz-López, J. Bernardino; Caminal-Montero, Luis; Martínez-Zapico, Aleida; Monfort, Jordi; Tío, Laura; Sánchez-Martín, Julio; Alegre-Sancho, Juan J.; Sáez-Comet, Luis; Pérez-Conesa, Mercedes; Corbera-Bellalta, Marc; García-Villanueva, M. Jesús; Fernández-Contreras, M. Encarnación; Sanchez-Pernaute, Olga; Blanco, Ricardo; Ortego-Centeno, Norberto; Ríos-Fernández, Raquel; Callejas, José L.; Fanlo-Mateo, Patricia; Martínez-Taboada, Víctor M.; Beretta, Lorenzo; Lunardi, Claudio; Cimmino, Marco A.; Gianfreda, Davide; Santilli, Daniele; Ramirez, Giuseppe A.; Soriano, Alessandra; Muratore, Francesco; Pazzola, Giulia; Addimanda, Olga; Wijmenga, Cisca; Witte, Torsten; Schirmer, Jan H.; Moosig, Frank; Schönau, Verena; Franke, Andre; Palm, Øyvind; Molberg, Øyvind; Diamantopoulos, Andreas P.; Carette, Simon; Cuthbertson, David; Forbess, Lindsy J.; Hoffman, Gary S.; Khalidi, Nader A.; Koening, Curry L.; Langford, Carol A.; McAlear, Carol A.; Moreland, Larry; Monach, Paul A.; Pagnoux, Christian; Seo, Philip; Spiera, Robert; Sreih, Antoine G.; Warrington, Kenneth J.; Ytterberg, Steven R.; Gregersen, Peter K.; Pease, Colin T.; Gough, Andrew; Green, Michael; Hordon, Lesley; Jarrett, Stephen; Watts, Richard; Levy, Sarah; Patel, Yusuf; Kamath, Sanjeet; Dasgupta, Bhaskar; Worthington, Jane; Koeleman, Bobby P.C.; de Bakker, Paul I.W.; Barrett, Jennifer H.; Salvarani, Carlo; Merkel, Peter A.; González-Gay, Miguel A.; Morgan, Ann W.; Martín, Javier

2015-01-01

We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10−40, OR = 1.73). A multivariate model including class II amino acids of HLA-DRβ1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1∗04. An omnibus test on polymorphic amino acid positions highlighted DRβ1 13 (p = 4.08 × 10−43) and HLA-DQα1 47 (p = 4.02 × 10−46), 56, and 76 (both p = 1.84 × 10−45) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10−6, OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10−6, OR = 1.20), and REL (rs115674477, p = 1.10 × 10−5, OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function. PMID:25817017

Involvement and prognosis value of CD8(+) T cells in giant cell arteritis.

PubMed

Samson, Maxime; Ly, Kim Heang; Tournier, Benjamin; Janikashvili, Nona; Trad, Malika; Ciudad, Marion; Gautheron, Alexandrine; Devilliers, Hervé; Quipourt, Valérie; Maurier, François; Meaux-Ruault, Nadine; Magy-Bertrand, Nadine; Manckoundia, Patrick; Ornetti, Paul; Maillefert, Jean-Francis; Besancenot, Jean-François; Ferrand, Christophe; Mesturoux, Laura; Labrousse, François; Fauchais, Anne-Laure; Saas, Philippe; Martin, Laurent; Audia, Sylvain; Bonnotte, Bernard

2016-08-01

CD8(+) T cells participate in the pathogenesis of some vasculitides. However, little is known about their role in Giant Cell Arteritis (GCA). This study was conducted to investigate CD8(+) T cell involvement in the pathogenesis of GCA. Analyses were performed at diagnosis and after 3 months of glucocorticoid treatment in 34 GCA patients and 26 age-matched healthy volunteers. Percentages of CD8(+) T-cell subsets, spectratype analysis of the TCR Vβ families of CD8(+) T cells, levels of cytokines and chemokines and immunohistochemistry of temporal artery biopsies (TAB) were assessed. Among total CD8(+) T cells, percentages of circulating cytotoxic CD8 T lymphocytes (CTL, CD3(+)CD8(+)perforin(+)granzymeB(+)), Tc17 (CD3(+)CD8(+)IL-17(+)), CD63(+)CD8(+) T cells and levels of soluble granzymes A and B were higher in patients than in controls, whereas the percentage of Tc1 cells (CD3(+)CD8(+)IFN-γ(+)) was similar. Moreover, CD8(+) T cells displayed a restricted TCR repertoire in GCA patients. Percentages of circulating CTL, Tc17 and soluble levels of granzymes A and B decreased after treatment. CXCR3 expression on CD8(+) T cells and its serum ligands (CXCL9, -10, -11) were higher in patients. Analyses of TAB revealed high expression of CXCL9 and -10 associated with infiltration by CXCR3(+)CD8(+) T cells expressing granzyme B and TiA1. The intensity of the CD8 T-cell infiltrate in TAB was predictive of the severity of the disease. This study demonstrates the implication and the prognostic value of CD8(+) T-cells in GCA and suggests that CD8(+) T-cells are recruited within the vascular wall through an interaction between CXCR3 and its ligands. Copyright © 2016 Elsevier Ltd. All rights reserved.

Extensive Karyotype Reorganization in the Fish Gymnotus arapaima (Gymnotiformes, Gymnotidae) Highlighted by Zoo-FISH Analysis

PubMed Central

Machado, Milla de Andrade; Pieczarka, Julio C.; Silva, Fernando H. R.; O'Brien, Patricia C. M.; Ferguson-Smith, Malcolm A.; Nagamachi, Cleusa Y.

2018-01-01

The genus Gymnotus (Gymnotiformes) contains over 40 species of freshwater electric fishes exhibiting a wide distribution throughout Central and South America, and being particularly prevalent in the Amazon basin. Cytogenetics has been an important tool in the cytotaxonomy and elucidation of evolutionary processes in this genus, including the unraveling the variety of diploid chromosome number (2n = from 34 to 54), the high karyotype diversity among species with a shared diploid number, different sex chromosome systems, and variation in the distribution of several Repetitive DNAs and colocation and association between those sequences. Recently whole chromosome painting (WCP) has been used for tracking the chromosomal evolution of the genus, showing highly reorganized karyotypes and the conserved synteny of the NOR bearing par within the clade G. carapo. In this study, painting probes derived from the chromosomes of G. carapo (GCA, 2n = 42, 30 m/sm + 12 st/a) were hybridized to the mitotic metaphases of G. arapaima (GAR, 2n = 44, 24 m/sm + 20 st/a). Our results uncovered chromosomal rearrangements and a high number of repetitive DNA regions. From the 12 chromosome pairs of G. carapo that can be individually differentiated (GCA1–3, 6, 7, 9, 14, 16, and 18–21), six pairs (GCA 1, 9, 14, 18, 20, 21) show conserved homology with GAR, five pairs (GCA 1, 9, 14, 20, 21) are also shared with cryptic species G. carapo 2n = 40 (34 m/sm + 6 st/a) and only the NOR bearing pair (GCA 20) is shared with G. capanema (GCP 2n = 34, 20 m/sm + 14 st/a). The remaining chromosomes are reorganized in the karyotype of GAR. Despite the close phylogenetic relationships of these species, our chromosome painting studies demonstrate an extensive reorganization of their karyotypes. PMID:29434621

Monograph on the use of the multivariate Gram Charlier series Type A

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

Hatayodom, T.; Heydt, G.

1978-01-01

The Gram-Charlier series in an infinite series expansion for a probability density function (pdf) in which terms of the series are Hermite polynomials. There are several Gram-Charlier series - the best known is Type A. The Gram-Charlier series, Type A (GCA) exists for both univariate and multivariate random variables. This monograph introduces the multivariate GCA and illustrates its use through several examples. A brief bibliography and discussion of Hermite polynomials is also included. 9 figures, 2 tables.

Cognitive outcome in childhood of birth weight discordant monochorionic twins: the long-term effects of fetal growth restriction.

PubMed

Swamy, Ravi Shankar; McConachie, Helen; Ng, Jane; Rankin, Judith; Korada, Murthy; Sturgiss, Stephen; Embleton, Nicholas D

2018-03-02

Intrauterine growth restriction (IUGR) is associated with poorer outcomes in later life. We used a monochorionic twin model with IUGR in one twin to determine its impact on growth and neurocognitive outcomes. Monochorionic twins with ≥20% birth weight discordance born in the north of England were eligible. Cognitive function was assessed using the British Ability Scales. The Strength and Difficulties Questionnaire was used to identify behavioural problems. Auxological measurements were collected. Generalised estimating equations were used to determine the effects of birth weight on cognition. Fifty-one monochorionic twin pairs were assessed at a mean age of 6.3 years. Mean birth weight difference was 664 g at a mean gestation of 34.7 weeks. The lighter twin had a General Conceptual Ability (GCA) score that was three points lower (Twin L -105.4 vs Twin H -108.4, 95% CI -0.9 to -5.0), and there was a significant positive association (B 0.59) of within-pair birth weight differences and GCA scores. Mathematics and memory skills showed the largest differences. The lighter twin at school age was shorter (mean difference 2.1 cm±0.7) and lighter (mean difference 1.9 kg±0.6). Equal numbers of lighter and heavier twins were reported to have behavioural issues. In a monochorionic twin cohort, fetal growth restriction results in lower neurocognitive scores in early childhood, and there remain significant differences in size. Longer term follow-up will be required to determine whether growth or cognitive differences persist in later child or adulthood, and whether there are any associated longer term metabolic sequelae. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Conjugated bile acids in gallbladder bile and serum as potential biomarkers for cholesterol polyps and adenomatous polyps.

PubMed

Zhao, Mei-Fen; Huang, Peng; Ge, Chun-Lin; Sun, Tao; Ma, Zhi-Gang; Ye, Fei-Fei

2016-02-28

To identify conjugated bile acids in gallbladder bile and serum as possible biomarkers for cholesterol polyps (CPs) and adenomatous polyps (APs). Gallbladder bile samples and serum samples were collected from 18 patients with CPs (CP group), 9 patients with APs (AP group), and 20 patients with gallstones (control group) from March to November, 2013. High performance liquid chromatography (HPLC) assay with ultraviolent detection was used to detect the concentration of 8 conjugated bile acids (glycocholic acid, GCA; taurocholic acid, TCA; glycochenodeoxycholic acid, GCDCA; taurochenodeoxycholic acid, TCDCA; glycodeoxycholic acid, GDCA; taurodeoxycholic acid, TDCA; taurolithocholic acid, TLCA; tauroursodeoxycholic acid, TUDCA) in bile samples and serum samples. The diagnostic efficacy of serum GCA, GCDCA and TCDCA was evaluated. These 8 conjugated bile acids in gallbladder bile and serum were completely identified within 10 minutes with good linearity (correlation coefficient: R>0.9900; linearity range: 3.91-500 µg/mL). Among these conjugated bile acids, the levels of gallbladder bile GCDCA and TCDCA in the CP group were significantly higher than those in the AP group (p<0.05). Furthermore, serum GCDCA and TCDCA as well as GCA were significantly higher in the AP group than the CP group (p<0.05). Serum GCDCA alone (≤12 µg/mL) had relatively better diagnostic efficacy than the other conjugated bile acids. The levels of serum GCA, GCDCA and TCDCA may be valuable for differentiation of APs and CPs.

Development of outcome measures for large-vessel vasculitis for use in clinical trials: opportunities, challenges, and research agenda.

PubMed

Direskeneli, Haner; Aydin, Sibel Z; Kermani, Tanaz A; Matteson, Eric L; Boers, Maarten; Herlyn, Karen; Luqmani, Raashid A; Neogi, Tuhina; Seo, Philip; Suppiah, Ravi; Tomasson, Gunnar; Merkel, Peter A

2011-07-01

Giant cell (GCA) and Takayasu's arteritis (TAK) are 2 forms of large-vessel vasculitis (LVV) that involve the aorta and its major branches. GCA has a predilection for the cranial branches, while TAK tends to affect the extracranial branches. Both disorders may also cause nonspecific constitutional symptoms. Although some clinical features are more common in one or the other disorder and the ages of initial presentation differ substantially, there is enough clinical and histopathologic overlap between these disorders that some investigators suggest GCA and TAK may be 2 processes within the spectrum of a single disease. There have been few randomized therapeutic trials completed in GCA, and none in TAK. The lack of therapeutic trials in LVV is only partially explained by the rarity of these diseases. It is likely that the lack of well validated outcome measures for LVV and uncertainties regarding trial design contribute to the paucity of trials for these diseases. An initiative to develop a core set of outcome measures for use in clinical trials of LVV was launched by the international OMERACT Vasculitis Working Group in 2009 and subsequently endorsed by the OMERACT community at the OMERACT 10 meeting. Aims of this initiative include: (1) to review the literature and existing data related to outcome assessments in LVV; (2) to obtain the opinion of experts and patients on disease content; and (3) to formulate a research agenda to facilitate a more data-based approach to outcomes development.

Development of Outcome Measures for Large-vessel Vasculitis for Use in Clinical Trials: Opportunities, Challenges, and Research Agenda

PubMed Central

DIRESKENELI, HANER; AYDIN, SIBEL Z.; KERMANI, TANAZ A.; MATTESON, ERIC L.; BOERS, MAARTEN; HERLYN, KAREN; LUQMANI, RAASHID A.; NEOGI, TUHINA; SEO, PHILIP; SUPPIAH, RAVI; TOMASSON, GUNNAR; MERKEL, PETER A.

2013-01-01

Giant cell (GCA) and Takayasu’s arteritis (TAK) are 2 forms of large-vessel vasculitis (LVV) that involve the aorta and its major branches. GCA has a predilection for the cranial branches, while TAK tends to affect the extracranial branches. Both disorders may also cause nonspecific constitutional symptoms. Although some clinical features are more common in one or the other disorder and the ages of initial presentation differ substantially, there is enough clinical and histopathologic overlap between these disorders that some investigators suggest GCA and TAK may be 2 processes within the spectrum of a single disease. There have been few randomized therapeutic trials completed in GCA, and none in TAK. The lack of therapeutic trials in LVV is only partially explained by the rarity of these diseases. It is likely that the lack of well validated outcome measures for LVV and uncertainties regarding trial design contribute to the paucity of trials for these diseases. An initiative to develop a core set of outcome measures for use in clinical trials of LVV was launched by the international OMERACT Vasculitis Working Group in 2009 and subsequently endorsed by the OMERACT community at the OMERACT 10 meeting. Aims of this initiative include: (1) to review the literature and existing data related to outcome assessments in LVV; (2) to obtain the opinion of experts and patients on disease content; and (3) to formulate a research agenda to facilitate a more data-based approach to outcomes development. PMID:21724719

Management of Large-Vessel Vasculitis With FDG-PET

PubMed Central

Soussan, Michael; Nicolas, Patrick; Schramm, Catherine; Katsahian, Sandrine; Pop, Gabriel; Fain, Olivier; Mekinian, Arsene

2015-01-01

Abstract We aimed to clarify the role of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the management of large-vessel vasculitis (LVV), focusing on 3 issues which are as follows: describe and determine the different FDG-PET criteria for the diagnosis of vascular inflammation, the performance of FDG-PET for the diagnosis of large-vessel inflammation in giant cell arteritis (GCA) patients, and the performance of FDG-PET to evaluate the disease inflammatory activity in Takayasu arteritis (TA) patients. MEDLINE, Cochrane Library, and EMBASE database were searched for articles that evaluated the value of FDG-PET in LVV, from January 2000 to December 2013. Inclusion criteria were American College of Rheumatology criteria for GCA or TA, definition PET positivity threshold, and >4 cases included. Sensitivity (Se) and specificity (Sp) of FDG-PET for the diagnosis of large-vessel inflammation were calculated from each included individual study, and then pooled for meta-analysis with a random-effects model. Twenty-one studies (413 patients, 299 controls) were included in the systematic review. FDG-PET showed FDG vascular uptake in 70% (288/413) of patients and 7% (22/299) of controls. Only vascular uptake equal to or higher than the liver uptake was significantly different between GCA/TA patients and controls (P < 0.001). The meta-analysis of GCA patients (4 studies, 57 patients) shows that FDG-PET has high Se and Sp for the diagnosis of large-vessel inflammation in GCA patients in comparison to controls, with a pooled Se at 90% (95% confidence interval [CI], 79%–93%) and a pooled Sp at 98% (95% CI, 94%–99%). The meta-analysis of TA patients (7 studies, 191 patients) shows that FDG-PET has a pooled Se at 87% (95% CI, 78%–93%) and Sp at 73% (95% CI, 63%–81%) for the assessment of disease activity in TA, with up to 84% Sp, with studies using National Institutes of Health criteria as the disease activity assessment scale. FDG-PET showed good performances in the diagnosis of large-vessel inflammation, with higher accuracy in GCA patients than in TA patients. Although a vascular uptake equal to or higher than the liver uptake appears to be a good criterion for the diagnosis of vascular inflammation, further studies are needed to define the threshold of significance as well as the clinical significance of the vascular uptake. PMID:25860208

Stable Isotopes, Multidisciplinary Studies, and the Leadership of J.G. Liou in UHP Metamorphism

NASA Astrophysics Data System (ADS)

Rumble, D.

2005-12-01

J.G. Liou has played a crucial role in improving knowledge of UHP metamorphism by leading multi-disciplinary, multi-institutional teams of researchers and by encouraging new investigators and providing them access to samples. Stable isotope geochemistry has made important contributions to understanding UHP metamorphism including: (1) The discovery of O- and H-isotope signatures of meteoric water in UHP rocks from China and Kazakhstan demonstrates that their protoliths originated at or near Earth's surface in a cold climate(a); (2) The mapping of contiguous tracts of outcrops extending over distances of 100 km where both eclogites and their wall rocks retain unusually low d18O and dD is consistent with the subduction and exhumation of UHP slabs as coherent structural units(b); (3) Analysis of samples from the Chinese Continental Scientific Drilling project reveals not only that UHP metamorphic rocks have not exchanged O-isotopes with mantle rocks while they were buried in the upper mantle but also that garnet peridotite slabs from the mantle have not exchanged with crustal wall rocks(c). Recent advances have resulted from multidisciplinary geochemical investigations. The analysis of zircons for both d18O and U-Pb established the age of cold climate, meteoric water alteration of protoliths to be Neoproterozoic for UHP rocks from Dabie and Sulu, China(d). Thus, O-isotopes plus age dating raises the possibility that evidence of snowball Earth conditions has been preserved in an unlikely host: UHP metamorphic rocks. A comparison of U-Pb, Sm-Nd, and Rb-Sr isotope data with analyses for d18O in coexisting minerals shows that discordant age dates correlate with mineral pairs that are not in O-isotope exchange equilibrium(e). It may be seen that multidisciplinary geochemical investigations provide mutually reinforcing data that greatly strengthens interpretations. New discoveries of de novo microdiamonds accompanied by multiphase mineral inclusions in UHP metamorphosed crustal rocks raise exciting possibilities for future stable isotope research on their origin(f). Micron-scale analytical techniques including ion microprobe, "Nano-SIMS", and UV-laser ablation, should be applied to the mineral assemblages to determine whether parent fluids were super-critical C-O-H fluids or carbonate-rich melts. (a) Geochim.Cosmochim.Acta (GCA) 59, 2859; Euro.J.Mineral 8, 317; GCA 61, 1658.(b) GCA 62, 3307.(c) Amer.Mineral. 90, 857.(d) GCA 66, 2299; GCA 68, 4145.(e) GCA 66, 625.(f) J.Metamorph.Geol. 21, 425.

Staging Options for the Air Force’s Electronic Combat Test Capability: a Cost Analysis

DTIC Science & Technology

1990-09-01

strategic in nature and completely different than daily operating decisions (20:6). Horngren , in his book Cost Accounting : A Managerial Emphasis...AFIT/GCA/LSY/90S-3 DTTC S E-191 J) C, STAGING OPTIONS FOR THE AIR FORCE’S ELECTRONIC COMBAT TEST CAPABILITY: A COST ANALYSIS THESIS Joseph J. Landino...Alternative Costs ......... 56 v AFIT/GCA/LSY/90S-3 Abstract This study’s purpose was to identify the lowest cost aircraft staging base( s ) for the Air

Experimental Tracking of Aerial Targets Using the Microflown Sensor

DTIC Science & Technology

2012-03-01

Classification ( MUSIC ) is widely known to be able to do that. Given n vector sensors, the theory hypothesizes the detection of 4n-2 uncorrelated sources...8217,’none’); %nxm 3D plot at freq of interest set(gca,’ZDir’,’reverse’) camup([0 1 0]); campos ([20 15 20]) title(figtitle) xlabel...gca,’ZDir’,’reverse’) camup([0 1 0]); 66 campos ([20 15 20]) title(figtitle) xlabel(’y axis’) ylabel(’x axis’) %phi - n

The use of the color Doppler ultrasonography in the diagnosis and monitoring of an atypical case of giant-cell arteritis.

PubMed

Martins, N; Polido-Pereira, J; Rodrigues, A M; Soares, F; Batista, P; Pereira da Silva, J A

2016-01-01

Giant Cell Arteritis (GCA) is a large vessels vasculitis that is typically characterised by headache, scalp tenderness, jaw claudication and visual disturbances. Temporal arteries color Doppler ultrasonography (CDUS) is a sensitive and non-invasive image technique used in the diagnosis of this disease. This work highlights the importance of CDUS in the diagnostic workup of GCA and also demonstrates it´s usefullness in the evaluation and documentation of the response to corticosteroids therapy in an atypical case of ACG.

Ground Controlled Approach Controller Training System (GCA-CTS) System Documentation.

DTIC Science & Technology

1980-06-01

064010 OVER 72 Al NAVTRAEQUIPCEN 77-C-0162-3 TABLE 8. GCA-CTS PHRASES (CONT) Number Phrase of Identi- Number Repeats fier Phrase 90) 4 170040 THIS WILL...radians/second)( Becomes 0.0 degrees/second. 121 F-. 0 .,- NAVTRAEQUIPCE.: 77-C-nfi2-3 ?.1-t Ac7uires Vi5: al Contac- "’ith Runwav. If the current...variables: ITMP : temporary for source of speech output Files created/changed: None Files referenced: None Notes: None 388 I I4; r I’, Al ൐a7 190

Circulating soluble adhesion molecules in patients with giant cell arteritis. Correlation between soluble intercellular adhesion molecule-1 (sICAM-1) concentrations and disease activity

PubMed Central

Coll-Vinent, B.; Vilardell, C.; Font, C.; Oristrell, J.; Hernandez-Rodrigu..., J.; Yague, J.; Urbano-Marquez, A.; Grau, J.; Cid, M.

1999-01-01

OBJECTIVE—To evaluate whether changes in concentrations of circulating adhesion molecules are related to disease activity in patients with giant cell arteritis (GCA).
METHODS—A sandwich ELISA was used to measure soluble intercellular adhesion molecule-1 (sICAM-1), sICAM-3, vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), and L-selectin (sL-selectin) in serum and plasma samples from patients with GCA. A cross sectional study was performed on 64 GCA patients at different activity stages and on 35 age and sex matched healthy donors. Thirteen of these patients were evaluated at the time of diagnosis and serially during follow up.
RESULTS—At the time of diagnosis, sICAM-1 concentrations were significantly higher in active GCA patients than in controls (mean (SD) 360.55 (129.78) ng/ml versus 243.25 (47.43) ng/ml, p<0.001). In contrast, sICAM-3, sVCAM-1, sE-selectin, and sL-selectin values did not differ from those obtained in normal donors. With corticosteroid administration, a decrease in sICAM-1 concentrations was observed, reaching normal values when clinical remission was achieved (263.18 (92.7) ng/ml globally, 293.59 (108.39) ng/ml in the group of patients in recent remission, and 236.83 (70.02) ng/ml in those in long term remission). In the 13 patients followed up longitudinally, sICAM-1 values also normalised with clinical remission (225.87 (64.25) ng/ml in patients in recent remission, and 256.29 (75.15) ng/ml in those in long term remission).
CONCLUSIONS—Circulating sICAM-1 concentrations clearly correlate with clinically apparent disease activity in GCA patients. Differences with results previously found in patients with other vasculitides may indicate that different pathogenic mechanisms contribute to vascular inflammation in different disorders.

 Keywords: adhesion molecules; giant cell arteritis; inflammation PMID:10364919

Regulation and therapeutic targeting of peptide-activated receptor guanylyl cyclases

PubMed Central

Potter, Lincoln R.

2016-01-01

Cyclic GMP is a ubiquitous second messenger that regulates a wide array of physiologic processes such as blood pressure, long bone growth, intestinal fluid secretion, phototransduction and lipolysis. Soluble and single-membrane-spanning enzymes called guanylyl cyclases (GC) synthesize cGMP. In humans, the latter group consists of GC-A, GC-B, GC-C, GC-E and GC-F, which are also known as NPR-A, NPR-B, StaR, Ret1-GC and Ret2-GC, respectively. Membrane GCs are activated by peptide ligands such as atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), C-type natriuretic peptide (CNP), guanylin, uroguanylin, heat stable enterotoxin and GC-activating proteins. Nesiritide and carperitide are clinically approved peptide-based drugs that activate GC-A. CD-NP is an experimental heart failure drug that primarily activates GC-B but also activates GC-A at high concentrations and is resistant to degradation. Inactivating mutations in GC-B cause acromesomelic dysplasia type Maroteaux dwarfism and chromosomal mutations that increase CNP concentrations are associated with Marfanoid-like skeletal overgrowth. Pump-based CNP infusions increase skeletal growth in a mouse model of the most common type of human dwarfism, which supports CNP/GC-B-based therapies for short stature diseases. Linaclotide is a peptide activator of GC-C that stimulates intestinal motility and is in late-stage clinical trials for the treatment of chronic constipation. This review discusses the discovery of cGMP, guanylyl cyclases, the general characteristics and therapeutic applications of GC-A, GC-B and GC-C, and emphasizes the regulation of transmembrane guanylyl cyclases by phosphorylation and ATP. PMID:21185863

A cardiac pathway of cyclic GMP-independent signaling of guanylyl cyclase A, the receptor for atrial natriuretic peptide

PubMed Central

Klaiber, Michael; Dankworth, Beatrice; Kruse, Martin; Hartmann, Michael; Nikolaev, Viacheslav O.; Yang, Ruey-Bing; Völker, Katharina; Gaßner, Birgit; Oberwinkler, Heike; Feil, Robert; Freichel, Marc; Groschner, Klaus; Skryabin, Boris V.; Frantz, Stefan; Birnbaumer, Lutz; Pongs, Olaf; Kuhn, Michaela

2011-01-01

Cardiac atrial natriuretic peptide (ANP) regulates arterial blood pressure, moderates cardiomyocyte growth, and stimulates angiogenesis and metabolism. ANP binds to the transmembrane guanylyl cyclase (GC) receptor, GC-A, to exert its diverse functions. This process involves a cGMP-dependent signaling pathway preventing pathological [Ca2+]i increases in myocytes. In chronic cardiac hypertrophy, however, ANP levels are markedly increased and GC-A/cGMP responses to ANP are blunted due to receptor desensitization. Here we show that, in this situation, ANP binding to GC-A stimulates a unique cGMP-independent signaling pathway in cardiac myocytes, resulting in pathologically elevated intracellular Ca2+ levels. This pathway involves the activation of Ca2+‐permeable transient receptor potential canonical 3/6 (TRPC3/C6) cation channels by GC-A, which forms a stable complex with TRPC3/C6 channels. Our results indicate that the resulting cation influx activates voltage-dependent L-type Ca2+ channels and ultimately increases myocyte Ca2+i levels. These observations reveal a dual role of the ANP/GC-A–signaling pathway in the regulation of cardiac myocyte Ca2+i homeostasis. Under physiological conditions, activation of a cGMP-dependent pathway moderates the Ca2+i-enhancing action of hypertrophic factors such as angiotensin II. By contrast, a cGMP-independent pathway predominates under pathophysiological conditions when GC-A is desensitized by high ANP levels. The concomitant rise in [Ca2+]i might increase the propensity to cardiac hypertrophy and arrhythmias. PMID:22027011

Visualisation of an nsPEF induced calcium wave using the genetically encoded calcium indicator GCaMP in U87 human glioblastoma cells.

PubMed

Carr, Lynn; Bardet, Sylvia M; Arnaud-Cormos, Delia; Leveque, Philippe; O'Connor, Rodney P

2018-02-01

Cytosolic, synthetic chemical calcium indicators are typically used to visualise the rapid increase in intracellular calcium ion concentration that follows nanosecond pulsed electric field (nsPEF) application. This study looks at the application of genetically encoded calcium indicators (GECIs) to investigate the spatiotemporal nature of nsPEF-induced calcium signals using fluorescent live cell imaging. Calcium responses to 44kV/cm, 10ns pulses were observed in U87-MG cells expressing either a plasma membrane targeted GECI (GCaMP5-G), or one cytosolically expressed (GCaMP6-S), and compared to the response of cells loaded with cytosolic or plasma membrane targeted chemical calcium indicators. Application of 100 pulses, to cells containing plasma membrane targeted indicators, revealed a wave of calcium across the cell initiating at the cathode side. A similar spatial wave was not observed with cytosolic indicators with mobile calcium buffering properties. The speed of the wave was related to pulse application frequency and it was not propagated by calcium induced calcium release. Copyright © 2017 Elsevier B.V. All rights reserved.

Separation of tartronic and glyceric acids by simulated moving bed chromatography.

PubMed

Coelho, Lucas C D; Filho, Nelson M L; Faria, Rui P V; Ferreira, Alexandre F P; Ribeiro, Ana M; Rodrigues, Alírio E

2018-08-17

The SMB unit developed by the Laboratory of Separation and Reaction Engineering (FlexSMB-LSRE ® ) was used to perform tartronic acid (TTA) and glyceric acid (GCA) separation and to validate the mathematical model in order to determine the optimum operating parameters of an industrial unit. The purity of the raffinate and extract streams in the experiments performed were 80% and 100%, respectively. The TTA and GCA productivities were 79 and 115 kg per liter of adsorbent per day, respectively and only 0.50 cubic meters of desorbent were required per kilogram of products. Under the optimum operating conditions, which were determined through an extensive simulation study based on the mathematical model developed to predict the performance of a real SMB unit, it was possible to achieve a productivity of 86 kg of TTA and 176 kg of GCA per cubic meter of adsorbent per day (considering the typical commercial purity value of 97% for both compounds) with an eluent consumption of 0.30 cubic meters per kilogram of products. Copyright © 2018 Elsevier B.V. All rights reserved.

An evaluation of the GCA respirable dust monitor 101-1.

PubMed

Marple, V A; Rubow, K L

1978-01-01

The GCA RDM 101-1 has been evaluated using aerosols of coal, Arizona road dust, silica, potash, and rock (copper ore) particles. The effects of the dust mass concentration, particle size distribution, and dust material on the instrument response were investigated. The instrument was found to measure the mass concentrations of respirable dust aerosols up to about 16 mg/m3 for coal and rock dust and about 20 mg/m3 for silica, potash, and Arizona road dust, providing there is not appreciable mass in the size range below approximateley 0.7 micrometer aerodynamic diameter.

A Novel Tumor Antigen and Foxp3 Dual Targeting Tumor Cell Vaccine Enhances the Immunotherapy in a Murine Model of Renal Cell Carcinoma

DTIC Science & Technology

2015-12-01

GTA TCC GAT GTC CAC AAT-30; CD206_fw 50-GCA AAT GGA GCC GTC TGT GC-30, CD206_rev 50-CTC GTG GAT CTC CGT GAC AC-30; Arg-1_fw 50- GTG AAG AAC CCA CGG TCT...GT-30, Arg-1_rev 50-CTG GTT GTC AGG GGA GTG TT-30; iNOS_fw 50-TGG TGG TGA CAA GCA CAT TT-30, iNOS_rev 50- AAG GCC AAA CAC AGC ATA CC-30; Cxcl9_fw 50

Electroconvulsive therapy selectively enhanced feedforward connectivity from fusiform face area to amygdala in major depressive disorder.

PubMed

Wang, Jiaojian; Wei, Qiang; Bai, Tongjian; Zhou, Xiaoqin; Sun, Hui; Becker, Benjamin; Tian, Yanghua; Wang, Kai; Kendrick, Keith

2017-12-01

Electroconvulsive therapy (ECT) has been widely used to treat the major depressive disorder (MDD), especially for treatment-resistant depression. However, the neuroanatomical basis of ECT remains an open problem. In our study, we combined the voxel-based morphology (VBM), resting-state functional connectivity (RSFC) and granger causality analysis (GCA) to identify the longitudinal changes of structure and function in 23 MDD patients before and after ECT. In addition, multivariate pattern analysis using linear support vector machine (SVM) was applied to classify 23 depressed patients from 25 gender, age and education matched healthy controls. VBM analysis revealed the increased gray matter volume of left superficial amygdala after ECT. The following RSFC and GCA analyses further identified the enhanced functional connectivity between left amygdala and left fusiform face area (FFA) and effective connectivity from FFA to amygdala after ECT, respectively. Moreover, SVM-based classification achieved an accuracy of 83.33%, a sensitivity of 82.61% and a specificity of 84% by leave-one-out cross-validation. Our findings indicated that ECT may facilitate the neurogenesis of amygdala and selectively enhance the feedforward cortical-subcortical connectivity from FFA to amygdala. This study may shed new light on the pathological mechanism of MDD and may provide the neuroanatomical basis for ECT. © The Author (2017). Published by Oxford University Press.

The Arf GEF GBF1 and Arf4 synergize with the sensory receptor cargo, rhodopsin, to regulate ciliary membrane trafficking.

PubMed

Wang, Jing; Fresquez, Theresa; Kandachar, Vasundhara; Deretic, Dusanka

2017-12-01

The small GTPase Arf4 and the Arf GTPase-activating protein (GAP) ASAP1 cooperatively sequester sensory receptor cargo into transport carriers targeted to primary cilia, but the input that drives Arf4 activation in this process remains unknown. Here, we show, by using frog retinas and recombinant human proteins, that during the carrier biogenesis from the photoreceptor Golgi/ trans -Golgi network (TGN) a functional complex is formed between Arf4, the Arf guanine nucleotide exchange factor (GEF) GBF1 and the light-sensing receptor, rhodopsin. Rhodopsin and Arf4 bind the regulatory N-terminal dimerization and cyclophillin-binding (DCB)-homology upstream of Sec7 (HUS) domain of GBF1. The complex is sensitive to Golgicide A (GCA), a selective inhibitor of GBF1 that accordingly blocks rhodopsin delivery to the cilia, without disrupting the photoreceptor Golgi. The emergence of newly synthesized rhodopsin in the endomembrane system is essential for GBF1-Arf4 complex formation in vivo Notably, GBF1 interacts with the Arf GAP ASAP1 in a GCA-resistant manner. Our findings indicate that converging signals on GBF1 from the influx of cargo into the Golgi/TGN and the feedback from Arf4, combined with input from ASAP1, control Arf4 activation during sensory membrane trafficking to primary cilia. © 2017. Published by The Company of Biologists Ltd.

The Relationship between Intrinsic Couplings of the Visual Word Form Area with Spoken Language Network and Reading Ability in Children and Adults

PubMed Central

Li, Yu; Zhang, Linjun; Xia, Zhichao; Yang, Jie; Shu, Hua; Li, Ping

2017-01-01

Reading plays a key role in education and communication in modern society. Learning to read establishes the connections between the visual word form area (VWFA) and language areas responsible for speech processing. Using resting-state functional connectivity (RSFC) and Granger Causality Analysis (GCA) methods, the current developmental study aimed to identify the difference in the relationship between the connections of VWFA-language areas and reading performance in both adults and children. The results showed that: (1) the spontaneous connectivity between VWFA and the spoken language areas, i.e., the left inferior frontal gyrus/supramarginal gyrus (LIFG/LSMG), was stronger in adults compared with children; (2) the spontaneous functional patterns of connectivity between VWFA and language network were negatively correlated with reading ability in adults but not in children; (3) the causal influence from LIFG to VWFA was negatively correlated with reading ability only in adults but not in children; (4) the RSFCs between left posterior middle frontal gyrus (LpMFG) and VWFA/LIFG were positively correlated with reading ability in both adults and children; and (5) the causal influence from LIFG to LSMG was positively correlated with reading ability in both groups. These findings provide insights into the relationship between VWFA and the language network for reading, and the role of the unique features of Chinese in the neural circuits of reading. PMID:28690507

The Relationship between Intrinsic Couplings of the Visual Word Form Area with Spoken Language Network and Reading Ability in Children and Adults.

PubMed

Li, Yu; Zhang, Linjun; Xia, Zhichao; Yang, Jie; Shu, Hua; Li, Ping

2017-01-01

Reading plays a key role in education and communication in modern society. Learning to read establishes the connections between the visual word form area (VWFA) and language areas responsible for speech processing. Using resting-state functional connectivity (RSFC) and Granger Causality Analysis (GCA) methods, the current developmental study aimed to identify the difference in the relationship between the connections of VWFA-language areas and reading performance in both adults and children. The results showed that: (1) the spontaneous connectivity between VWFA and the spoken language areas, i.e., the left inferior frontal gyrus/supramarginal gyrus (LIFG/LSMG), was stronger in adults compared with children; (2) the spontaneous functional patterns of connectivity between VWFA and language network were negatively correlated with reading ability in adults but not in children; (3) the causal influence from LIFG to VWFA was negatively correlated with reading ability only in adults but not in children; (4) the RSFCs between left posterior middle frontal gyrus (LpMFG) and VWFA/LIFG were positively correlated with reading ability in both adults and children; and (5) the causal influence from LIFG to LSMG was positively correlated with reading ability in both groups. These findings provide insights into the relationship between VWFA and the language network for reading, and the role of the unique features of Chinese in the neural circuits of reading.

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging of macrophages in large vessel vasculitis: Current status and future prospects.

PubMed

Jiemy, William Febry; Heeringa, Peter; Kamps, Jan A A M; van der Laken, Conny J; Slart, Riemer H J A; Brouwer, Elisabeth

2018-05-03

Macrophages are key players in the pathogenesis of large-vessel vasculitis (LVV) and may serve as a target for diagnostic imaging of LVV. The radiotracer, 18 F-FDG has proven to be useful in the diagnosis of giant cell arteritis (GCA), a form of LVV. Although uptake of 18 F-FDG is high in activated macrophages, it is not a specific radiotracer as its uptake is high in any proliferating cell and other activated immune cells resulting in high non-specific background radioactivity especially in aging and atherosclerotic vessels which dramatically lowers the diagnostic accuracy. Evidence also exists that the sensitivity of 18 F-FDG PET drops in patients upon glucocorticoid treatment. Therefore, there is a clinical need for more specific radiotracers in imaging GCA to improve diagnostic accuracy. Numerous clinically established and newly developed macrophage targeted radiotracers for oncological and inflammatory diseases can potentially be utilized for LVV imaging. These tracers are more target specific and therefore may provide lower background radioactivity, higher diagnostic accuracy and the ability to assess treatment effectiveness. However, current knowledge regarding macrophage subsets in LVV lesions is limited. Further understanding regarding macrophage subsets in vasculitis lesion is needed for better selection of tracers and new targets for tracer development. This review summarizes the development of macrophage targeted tracers in the last decade and the potential application of macrophage targeted tracers currently used in other inflammatory diseases in imaging LVV. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Is intimal hyperplasia a marker of neuro-ophthalmic complications of giant cell arteritis?

PubMed

Makkuni, D; Bharadwaj, A; Wolfe, K; Payne, S; Hutchings, A; Dasgupta, B

2008-04-01

The ischaemic complications of giant cell arteritis (GCA) such as blindness and stroke may result from luminal narrowing of the affected arteries. This study focuses on the association between the severity of intimal proliferation on temporal artery biopsy (TAB) histology and neuro-ophthalmic complications (NOCs) of GCA. We identified 30 cases of biopsy-proven temporal arteritis. One histopathologist (blinded to the clinical details) evaluated the TAB specimens and categorized the degree of maximum stenosis due to intimal hyperplasia into four grades: grade 1 is <50% luminal occlusion due to intimal hyperplasia, grade 2 is 50-75%, grade 3 is >75% and grade 4 is complete luminal occlusion. A second histopathologist (also blinded to the clinical details) independently evaluated the TAB specimens using the same grading system. The NOCs in these patients were noted after a case record review. Of the 30 patients, 12 had NOC-10 with eye complications (complete visual loss, anterior ischaemic neuropathy, visual field defects), one patient had cerebral infarcts and one had both cerebral infarcts and vision loss. There was evidence for a statistically significant trend of NOC associated with higher intimal hyperplasia scores (P = 0.001). The scores of the histopathologists agreed for 23 (77%) patients and differed by 1 category for the remaining 7 (kappa-statistic 0.88). Our study suggests that the degree of intimal hyperplasia on TAB histology (routinely available to all hospital units) seems to be closely associated with NOCs of GCA. The study highlights the possible prognostic as well as diagnostic role of the biopsy. We feel that intimal hyperplasia noted in biopsy specimens may help us in the risk stratification of GCA patients and targeting of appropriate and novel therapies.

Imaging Ca2+ nanosparks in heart with a new targeted biosensor.

PubMed

Shang, Wei; Lu, Fujian; Sun, Tao; Xu, Jiejia; Li, Lin-Lin; Wang, Yanru; Wang, Gang; Chen, Liangyi; Wang, Xianhua; Cannell, Mark B; Wang, Shi-Qiang; Cheng, Heping

2014-01-31

In cardiac dyads, junctional Ca2+ directly controls the gating of the ryanodine receptors (RyRs), and is itself dominated by RyR-mediated Ca2+ release from the sarcoplasmic reticulum. Existing probes do not report such local Ca2+ signals because of probe diffusion, so a junction-targeted Ca2+ sensor should reveal new information on cardiac excitation-contraction coupling and its modification in disease states. To investigate Ca2+ signaling in the nanoscopic space of cardiac dyads by targeting a new sensitive Ca2+ biosensor (GCaMP6f) to the junctional space. By fusing GCaMP6f to the N terminus of triadin 1 or junctin, GCaMP6f-triadin 1/junctin was targeted to dyadic junctions, where it colocalized with t-tubules and RyRs after adenovirus-mediated gene transfer. This membrane protein-tagged biosensor displayed ≈4× faster kinetics than native GCaMP6f. Confocal imaging revealed junctional Ca2+ transients (Ca2+ nanosparks) that were ≈50× smaller in volume than conventional Ca2+ sparks (measured with diffusible indicators). The presence of the biosensor did not disrupt normal Ca2+ signaling. Because no indicator diffusion occurred, the amplitude and timing of release measurements were improved, despite the small recording volume. We could also visualize coactivation of subclusters of RyRs within a single junctional region, as well as quarky Ca2+ release events. This new, targeted biosensor allows selective visualization and measurement of nanodomain Ca2+ dynamics in intact cells and can be used to give mechanistic insights into dyad RyR operation in health and in disease states such as when RyRs become orphaned.

The Effect of Pressure on Siderophile-Element (Ni, Co, Mo, W, and P) Metal-Silicate Partition Coefficients

NASA Astrophysics Data System (ADS)

Righter, K.; Drake, M. J.

1995-09-01

Quantification of the effect of pressure on siderophile element metal-silicate partition coefficients (D) is essential in modelling the accretion histories of the the Earth and terrestrial planets [1], as metal-silicate equilibria may have been set over a range of pressures [2]. We report siderophile element partition coefficients from metal-silicate equilibrium experiments done at 10 and 15 kb, and 1300 degrees C. These new results show that metal-silicate partition coefficients for Ni (Fig. 1), Co, and P decrease with increasing pressure (at constant T and relative fO(sub)2), while those for Mo and W increase. Experiments were done in a 1/2" piston cylinder apparatus, with T, P and fO(sub)2 controlled and monitored as described in a previous study [3]. Synthetic basalt [see 3] powder, doped with 5 wt% levels of either MoO3, WO3 or apatite, was loaded into Fe54Ni29Co17 or Fe64Ni36 tubing, which was closed either by welding or plugging the open ends with small, tapered caps of the same alloy composition. The samples were quenched after 4 to 6 hrs. The metal and glass in the run products are then analyzed by electron microprobe to obtain a solid metal/liquid silicate (SM/LS) partition coefficient for a given element (D = wt% element in metal/ wt% element in glass). For several experiments, NiS was added as a sulfur source, and thus stabilizing a sulfur-bearing metallic liquid. For these experiments, both solid metal/ liquid silicate and liquid metal/ liquid silicate (LM/LS) partition coefficients are reported (Table 1). In order to isolate the effect of pressure on siderophile element partition coefficients, we have compared our results at high pressures to calculated 1 bar values at the same T and fO(sub)2 as our experiments (based on experiments of [4 - 11]; see results for Ni in Fig. 1; data from [3] and this study). The effect of pressure and other intensive variables on metal-silicate D's can be quantified using the thermodynamically-based relation: lnD (metal/silicate) = a/T + b + clnfO(sub)2 + dln(1-2X(sub)S) + e(P-1)/T. (1) Values for a, b, c, d and e were determined by multiple linear regression of the 1 bar experimental data cited above, together with data from this study and available high pressure experimental data [3, 12 - 16]. Equation 1 can be used to predict the abundances of the siderophile elements in a planetary mantle that has undergone a metal separation event, at a specific T, P, fO(sub)2 and metal sulfur content. Such calculations for Mars indicate that metal segregation in the Martian mantle (based on SNC meteorite analyses) may have occurred at low pressures, in agreement with the conclusions of several other studies [17, 18, 19]. Similar calculations for Earth indicate that the upper mantle abundances of the siderophile elements are unlikely to have been set by simple metal-silicate equilibrium at pressures less than 100 kb. References: [1] Drake M. J. (1989) Z. Naturforsch., 44a, 883-890. [2] Newsom H. (1992] LPI Tech. Rpt. 92-03, 42-43. [3] Righter K. et al. (1995) LPS XXVI, 1169-1170. [4] Hillgren V. J. (1993) Ph.D. Thesis, Univ. of Arizona, Tucson. [5] Capobianco C. J. and Amelin A. (1994) GCA, 58, 125-140. [6] Schmitt et al. (1989) GCA, 53, 173-186. [7] Newsom H. and Drake M. J. (1982) GCA, 46, 2483-2489. [8] Newsom H. and Drake M. J. (1983) GCA, 47, 93-100. [9] Lodders K. and Palme H. (1991) EPSL, 113, 311-324. [10] Jones J. H. and Drake M. J. (1986) Nature, 322, 221-228. [11] Holzheid A. et al. (1994) GCA, 58, 1975-1981. [12] Thibault Y. and Walter M. J. (1994) GCA, 59, 991-1002. [13] Hillgren V. J. et al. (1994) Science, 264, 1442-1445. [14] Walker D. et al. (1993) Science, 262, 1858-1861. [15] Peach C. L. and Mathez E. A. (1993) GCA, 57, 3013-3032. [16] Seifert et al. (1988) GCA, 52, 603-616. [17] Drake M. J. et al. (1995) LPS XXVI, 345-346. [18] Gaetani G. A. and Grove T. L. (1995) LPS XXVI, 437-438. [19] Treiman A. H. et al. (1986) GCA, 50, 1071-1091. Acknowledgment: NASA Grant NAGW 3348 Table 1 shows a summary of experimental results.

Electrical Integration of Human Embryonic Stem Cell-Derived Cardiomyocytes in a Guinea Pig Chronic Infarct Model

PubMed Central

Shiba, Yuji; Filice, Dominic; Fernandes, Sarah; Minami, Elina; Dupras, Sarah K.; Van Biber, Benjamin; Trinh, Peter; Hirota, Yusuke; Gold, Joseph D.; Viswanathan, Mohan; Laflamme, Michael A.

2014-01-01

Background Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were recently shown to be capable of electromechanical integration following their direct injection into intact or recently injured guinea pig hearts, and hESC-CM transplantation in recently injured hearts correlated with improvements in contractile function and a reduction in the incidence of arrhythmias. The present study was aimed at determining the ability of hESC-CMs to integrate and modulate electrical stability following transplantation in a chronic model of cardiac injury. Methods & Results At 28 days following cardiac cryoinjury, guinea pigs underwent intra-cardiac injection of hESC-CMs, non-cardiac hESC-derivatives (non-CMs) or vehicle. Histology confirmed partial remuscularization of the infarct zone in hESC-CM recipients, while non-CM recipients showed heterogeneous xenografts. The three experimental groups showed no significant difference in the left ventricular dimensions or fractional shortening by echocardiography or in the incidence of spontaneous arrhythmias by telemetric monitoring. While recipients of hESC-CMs and vehicle showed a similar incidence of arrhythmias induced by programmed electrical stimulation at 4-weeks post-transplantation, non-CM recipients proved to be highly inducible, with a ~3-fold greater incidence of induced arrhythmias. In parallel studies, we investigated the ability of hESC-CMs to couple with host myocardium in chronically injured hearts by the intravital imaging of hESC-CM grafts that stably expressed a fluorescent reporter of graft activation, the genetically-encoded calcium sensor GCaMP3. In this work, we found that only ~38% (5 of 13) of recipients of GCaMP3+ hESC-CMs showed fluorescent transients that were coupled to the host electrocardiogram. Conclusions hESC-CMs engraft in chronically injured hearts without increasing the incidence of arrhythmias, but their electromechanical integration is more limited than was previously reported following their transplantation in a subacute injury model. Moreover, non-CM grafts may promote arrhythmias under certain conditions, a finding that underscores the need for input preparations of high cardiac purity. PMID:24516260

Breeding maize as biogas substrate in Central Europe: I. Quantitative-genetic parameters for testcross performance.

PubMed

Grieder, Christoph; Dhillon, Baldev S; Schipprack, Wolfgang; Melchinger, Albrecht E

2012-04-01

Biofuels have gained importance recently and the use of maize biomass as substrate in biogas plants for production of methane has increased tremendously in Germany. The objectives of our research were to (1) estimate variance components and heritability for different traits relevant to biogas production in testcrosses (TCs) of maize, (2) study correlations among traits, and (3) discuss strategies to breed maize as a substrate for biogas fermenters. We evaluated 570 TCs of 285 diverse dent maize lines crossed with two flint single-cross testers in six environments. Data were recorded on agronomic and quality traits, including dry matter yield (DMY), methane fermentation yield (MFY), and methane yield (MY), the product of DMY and MFY, as the main target trait. Estimates of variance components showed general combining ability (GCA) to be the major source of variation. Estimates of heritability exceeded 0.67 for all traits and were even much greater in most instances. Methane yield was perfectly correlated with DMY but not with MFY, indicating that variation in MY is primarily determined by DMY. Further, DMY had a larger heritability and coefficient of genetic variation than MFY. Hence, for improving MY, selection should primarily focus on DMY rather than MFY. Further, maize breeding for biogas production may diverge from that for forage production because in the former case, quality traits seem to be of much lower importance.

Functional imaging of hippocampal place cells at cellular resolution during virtual navigation

PubMed Central

Dombeck, Daniel A.; Harvey, Christopher D.; Tian, Lin; Looger, Loren L.; Tank, David W.

2010-01-01

Spatial navigation is a widely employed behavior in rodent studies of neuronal circuits underlying cognition, learning and memory. In vivo microscopy combined with genetically-encoded indicators provides important new tools to study neuronal circuits, but has been technically difficult to apply during navigation. We describe methods to image the activity of hippocampal CA1 neurons with sub-cellular resolution in behaving mice. Neurons expressing the genetically encoded calcium indicator GCaMP3 were imaged through a chronic hippocampal window. Head-fixed mice performed spatial behaviors within a setup combining a virtual reality system and a custom built two-photon microscope. Populations of place cells were optically identified, and the correlation between the location of their place fields in the virtual environment and their anatomical location in the local circuit was measured. The combination of virtual reality and high-resolution functional imaging should allow for a new generation of studies to probe neuronal circuit dynamics during behavior. PMID:20890294

A criteria and indicators monitoring framework for food forestry embedded in the principles of ecological restoration.

PubMed

Park, Hyeone; Higgs, Eric

2018-02-02

Food forestry is a burgeoning practice in North America, representing a strong multifunctional approach that combines agriculture, forestry, and ecological restoration. The Galiano Conservancy Association (GCA), a community conservation, restoration, and educational organization on Galiano Island, British Columbia in Canada, recently has created two food forests on their protected forested lands: one with primarily non-native species and the other comprising native species. These projects, aimed at food production, education, and promotion of local food security and sustainability, are also intended to contribute to the overall ecological integrity of the landscape. Monitoring is essential for assessing how effectively a project is meeting its goal and thus informing its adaptive management. Yet, presently, there are no comprehensive monitoring frameworks for food forestry available. To fill this need, this study developed a generic Criteria and Indicators (C&I) monitoring framework for food forestry, embedded in ecological restoration principles, by employing qualitative content analysis of 61 literature resources and semi-structured interviews with 16 experts in the fields of food forestry and ecological restoration. The generic C&I framework comprises 14 criteria, 39 indicators, and 109 measures and is intended to guide a comprehensive and systematic assessment for food forest projects. The GCA adapted the generic C&I framework to develop a customized monitoring framework. The Galiano C&I monitoring framework has comprehensive suite of monitoring parameters, which are collectively address multiple values and goals.

0.35-μm excimer DUV photolithography process

NASA Astrophysics Data System (ADS)

Arugu, Donald O.; Green, Kent G.; Nunan, Peter D.; Terbeek, Marcel; Crank, Sue E.; Ta, Lam; Capsuto, Elliott S.; Sethi, Satyendra S.

1993-08-01

It is becoming increasingly clear that DUV excimer laser based imaging will be one of the technologies for printing sub-half micron devices. This paper reports the investigation of 0.35 micrometers photolithography process using chemically amplified DUV resists on organic anti- reflective coating (ARC). Production data from the GCA XLS excimer DUV tools with nominal gate width of 0.35 micrometers lines, 0.45 micrometers spaces was studied to demonstrate device production worthiness. This data included electrical yield information for device characterization. Exposure overlay was done by mixing and matching DUV and I-line GCA steppers for critical and non critical levels respectively. Working isolated transistors down to 0.2 micrometers have been demonstrated.

Prolonged, brain-wide expression of nuclear-localized GCaMP3 for functional circuit mapping

PubMed Central

Kim, Christina K.; Miri, Andrew; Leung, Louis C.; Berndt, Andre; Mourrain, Philippe; Tank, David W.; Burdine, Rebecca D.

2014-01-01

Larval zebrafish offer the potential for large-scale optical imaging of neural activity throughout the central nervous system; however, several barriers challenge their utility. First, ~panneuronal probe expression has to date only been demonstrated at early larval stages up to 7 days post-fertilization (dpf), precluding imaging at later time points when circuits are more mature. Second, nuclear exclusion of genetically-encoded calcium indicators (GECIs) limits the resolution of functional fluorescence signals collected during imaging. Here, we report the creation of transgenic zebrafish strains exhibiting robust, nuclearly targeted expression of GCaMP3 across the brain up to at least 14 dpf utilizing a previously described optimized Gal4-UAS system. We confirmed both nuclear targeting and functionality of the modified probe in vitro and measured its kinetics in response to action potentials (APs). We then demonstrated in vivo functionality of nuclear-localized GCaMP3 in transgenic zebrafish strains by identifying eye position-sensitive fluorescence fluctuations in caudal hindbrain neurons during spontaneous eye movements. Our methodological approach will facilitate studies of larval zebrafish circuitry by both improving resolution of functional Ca2+ signals and by allowing brain-wide expression of improved GECIs, or potentially any probe, further into development. PMID:25505384

Imaging calcium microdomains within entire astrocyte territories and endfeet with GCaMPs expressed using adeno-associated viruses

PubMed Central

Shigetomi, Eiji; Bushong, Eric A.; Haustein, Martin D.; Tong, Xiaoping; Jackson-Weaver, Olan; Kracun, Sebastian; Xu, Ji; Sofroniew, Michael V.; Ellisman, Mark H.

2013-01-01

Intracellular Ca2+ transients are considered a primary signal by which astrocytes interact with neurons and blood vessels. With existing commonly used methods, Ca2+ has been studied only within astrocyte somata and thick branches, leaving the distal fine branchlets and endfeet that are most proximate to neuronal synapses and blood vessels largely unexplored. Here, using cytosolic and membrane-tethered forms of genetically encoded Ca2+ indicators (GECIs; cyto-GCaMP3 and Lck-GCaMP3), we report well-characterized approaches that overcome these limitations. We used in vivo microinjections of adeno-associated viruses to express GECIs in astrocytes and studied Ca2+ signals in acute hippocampal slices in vitro from adult mice (aged ∼P80) two weeks after infection. Our data reveal a sparkling panorama of unexpectedly numerous, frequent, equivalently scaled, and highly localized Ca2+ microdomains within entire astrocyte territories in situ within acute hippocampal slices, consistent with the distribution of perisynaptic branchlets described using electron microscopy. Signals from endfeet were revealed with particular clarity. The tools and experimental approaches we describe in detail allow for the systematic study of Ca2+ signals within entire astrocytes, including within fine perisynaptic branchlets and vessel-associated endfeet, permitting rigorous evaluation of how astrocytes contribute to brain function. PMID:23589582

Imaging calcium microdomains within entire astrocyte territories and endfeet with GCaMPs expressed using adeno-associated viruses.

PubMed

Shigetomi, Eiji; Bushong, Eric A; Haustein, Martin D; Tong, Xiaoping; Jackson-Weaver, Olan; Kracun, Sebastian; Xu, Ji; Sofroniew, Michael V; Ellisman, Mark H; Khakh, Baljit S

2013-05-01

Intracellular Ca(2+) transients are considered a primary signal by which astrocytes interact with neurons and blood vessels. With existing commonly used methods, Ca(2+) has been studied only within astrocyte somata and thick branches, leaving the distal fine branchlets and endfeet that are most proximate to neuronal synapses and blood vessels largely unexplored. Here, using cytosolic and membrane-tethered forms of genetically encoded Ca(2+) indicators (GECIs; cyto-GCaMP3 and Lck-GCaMP3), we report well-characterized approaches that overcome these limitations. We used in vivo microinjections of adeno-associated viruses to express GECIs in astrocytes and studied Ca(2+) signals in acute hippocampal slices in vitro from adult mice (aged ∼P80) two weeks after infection. Our data reveal a sparkling panorama of unexpectedly numerous, frequent, equivalently scaled, and highly localized Ca(2+) microdomains within entire astrocyte territories in situ within acute hippocampal slices, consistent with the distribution of perisynaptic branchlets described using electron microscopy. Signals from endfeet were revealed with particular clarity. The tools and experimental approaches we describe in detail allow for the systematic study of Ca(2+) signals within entire astrocytes, including within fine perisynaptic branchlets and vessel-associated endfeet, permitting rigorous evaluation of how astrocytes contribute to brain function.

Natriuretic Peptide Receptor Guanylyl Cyclase-A Protects Podocytes from Aldosterone-Induced Glomerular Injury

PubMed Central

Ogawa, Yoshihisa; Yokoi, Hideki; Kasahara, Masato; Mori, Kiyoshi; Kato, Yukiko; Kuwabara, Takashige; Imamaki, Hirotaka; Kawanishi, Tomoko; Koga, Kenichi; Ishii, Akira; Tokudome, Takeshi; Kishimoto, Ichiro; Sugawara, Akira; Nakao, Kazuwa

2012-01-01

Natriuretic peptides produced by the heart in response to cardiac overload exert cardioprotective and renoprotective effects by eliciting natriuresis, reducing BP, and inhibiting cell proliferation and fibrosis. These peptides also antagonize the renin-angiotensin-aldosterone system, but whether this mechanism contributes to their renoprotective effect is unknown. Here, we examined the kidneys of mice lacking the guanylyl cyclase-A (GC-A) receptor for natriuretic peptides under conditions of high aldosterone and high dietary salt. After 4 weeks of administering aldosterone and a high-salt diet, GC-A knockout mice, but not wild-type mice, exhibited accelerated hypertension with massive proteinuria. Aldosterone-infused GC-A knockout mice had marked mesangial expansion, segmental sclerosis, severe podocyte injury, and increased oxidative stress. Reducing the BP with hydralazine failed to lessen such changes; in contrast, blockade of the renin-angiotensin-aldosterone system markedly reduced albuminuria, ameliorated podocyte injury, and reduced oxidative stress. Furthermore, treatment with the antioxidant tempol significantly reduced albuminuria and abrogated the histologic changes. In cultured podocytes, natriuretic peptides inhibited aldosterone-induced mitogen-activated protein kinase phosphorylation. Taken together, these results suggest that renoprotective properties of the endogenous natriuretic peptide/GC-A system may result from the local inhibition of the renin-angiotensin-aldosterone system and oxidative stress in podocytes. PMID:22652704

Generation of a Homozygous Transgenic Rat Strain Stably Expressing a Calcium Sensor Protein for Direct Examination of Calcium Signaling.

PubMed

Szebényi, Kornélia; Füredi, András; Kolacsek, Orsolya; Pergel, Enikő; Bősze, Zsuzsanna; Bender, Balázs; Vajdovich, Péter; Tóvári, József; Homolya, László; Szakács, Gergely; Héja, László; Enyedi, Ágnes; Sarkadi, Balázs; Apáti, Ágota; Orbán, Tamás I

2015-08-03

In drug discovery, prediction of selectivity and toxicity require the evaluation of cellular calcium homeostasis. The rat is a preferred laboratory animal for pharmacology and toxicology studies, while currently no calcium indicator protein expressing rat model is available. We established a transgenic rat strain stably expressing the GCaMP2 fluorescent calcium sensor by a transposon-based methodology. Zygotes were co-injected with mRNA of transposase and a CAG-GCaMP2 expressing construct, and animals with one transgene copy were pre-selected by measuring fluorescence in blood cells. A homozygous rat strain was generated with high sensor protein expression in the heart, kidney, liver, and blood cells. No pathological alterations were found in these animals, and fluorescence measurements in cardiac tissue slices and primary cultures demonstrated the applicability of this system for studying calcium signaling. We show here that the GCaMP2 expressing rat cardiomyocytes allow the prediction of cardiotoxic drug side-effects, and provide evidence for the role of Na(+)/Ca(2+) exchanger and its beneficial pharmacological modulation in cardiac reperfusion. Our data indicate that drug-induced alterations and pathological processes can be followed by using this rat model, suggesting that transgenic rats expressing a calcium-sensitive protein provide a valuable system for pharmacological and toxicological studies.

Functional imaging of cortical feedback projections to the olfactory bulb

PubMed Central

Rothermel, Markus; Wachowiak, Matt

2014-01-01

Processing of sensory information is substantially shaped by centrifugal, or feedback, projections from higher cortical areas, yet the functional properties of these projections are poorly characterized. Here, we used genetically-encoded calcium sensors (GCaMPs) to functionally image activation of centrifugal projections targeting the olfactory bulb (OB). The OB receives massive centrifugal input from cortical areas but there has been as yet no characterization of their activity in vivo. We focused on projections to the OB from the anterior olfactory nucleus (AON), a major source of cortical feedback to the OB. We expressed GCaMP selectively in AON projection neurons using a mouse line expressing Cre recombinase (Cre) in these neurons and Cre-dependent viral vectors injected into AON, allowing us to image GCaMP fluorescence signals from their axon terminals in the OB. Electrical stimulation of AON evoked large fluorescence signals that could be imaged from the dorsal OB surface in vivo. Surprisingly, odorants also evoked large signals that were transient and coupled to odorant inhalation both in the anesthetized and awake mouse, suggesting that feedback from AON to the OB is rapid and robust across different brain states. The strength of AON feedback signals increased during wakefulness, suggesting a state-dependent modulation of cortical feedback to the OB. Two-photon GCaMP imaging revealed that different odorants activated different subsets of centrifugal AON axons and could elicit both excitation and suppression in different axons, indicating a surprising richness in the representation of odor information by cortical feedback to the OB. Finally, we found that activating neuromodulatory centers such as basal forebrain drove AON inputs to the OB independent of odorant stimulation. Our results point to the AON as a multifunctional cortical area that provides ongoing feedback to the OB and also serves as a descending relay for other neuromodulatory systems. PMID:25071454

Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy and safety of a green coffee bean extract in overweight subjects

PubMed Central

Vinson, Joe A; Burnham, Bryan R; Nagendran, Mysore V

2012-01-01

Background Adult weight gain and obesity have become worldwide problems. Issues of cost and potential side effects of prescription weight loss drugs have led overweight and obese adults to try nutraceuticals that may aid weight loss. One promising nutraceutical is green coffee extract, which contains high concentrations of chlorogenic acids that are known to have health benefits and to influence glucose and fat metabolism. A 22-week crossover study was conducted to examine the efficacy and safety of a commercial green coffee extract product GCA™ at reducing weight and body mass in 16 overweight adults. Methods Subjects received high-dose GCA (1050 mg), low-dose GCA (700 mg), or placebo in separate six-week treatment periods followed by two-week washout periods to reduce any influence of preceding treatment. Treatments were counterbalanced between subjects. Primary measurements were body weight, body mass index, and percent body fat. Heart rate and blood pressure were also measured. Results Significant reductions were observed in body weight (−8.04 ± 2.31 kg), body mass index (−2.92 ± 0.85 kg/m2), and percent body fat (−4.44% ± 2.00%), as well as a small decrease in heart rate (−2.56 ± 2.85 beats per minute), but with no significant changes to diet over the course of the study. Importantly, the decreases occurred when subjects were taking GCA. Body mass index for six subjects shifted from preobesity to the normal weight range (<25.00 kg/m2). Conclusion The results are consistent with human and animal studies and a meta-analysis of the efficacy of green coffee extract in weight loss. The results suggest that GCA may be an effective nutraceutical in reducing weight in preobese adults, and may be an inexpensive means of preventing obesity in overweight adults. PMID:22291473

Ecological Risk Assessment of Munitions Compounds on Coral and Coral Reef Health

DTIC Science & Technology

2014-01-01

C308R Porites lobata Maunalua Bay, Oahu, HI K5 TAG GTG GGG AAT CAA ACG GC C307F C309F Porites lobata La Perouse, Maui, HI 3-3 GCT GGC TTA CAG...GGA ATT TTA ACT TCA AGC 24 41.7% 54°C 2.08 Kb this work Porites mtDNA cobR A GAT TCT CTT TGC GCA GTG GCA TAG G 25 52.0% 59°C this work Porites mtDNA...47.6% 52°C 2.14 Kb this work Porites mtDNA nad5(5’)R K CCA ACT GTG CAG ACT TTC CAA CC 23 52.2% 57°C this work References and further reading

The Influence of Intrinsic and Extrinsic Factors on Neurogenesis

DTIC Science & Technology

2008-07-31

ACG AAT TGA GCA ATA ACG GTG ATG GCG ATA GTA AGA ACA GTT C 49 Table II-2. Sequence information and physical characteristics of...CTC TGA GCT AGT 550 50 24 60.15 3’mAT-O GTG ACA CTA GCA GAC CAG ATT CCT 550 50 24 61.08 5’mAT-N GCC TCT GAG CTA GTA TGT GTC ATC 274 50 24 59.46 3...8217mAT-N CCA TCA CCT TCT CCT TTC TAG GTC 274 50 24 61.64 5’rAT-O TTT AGC TCA GTG GTA GAG CGC 257 52 21 56 3’rAT-O GTT TCT GCC CTT TCC AAC TGC 257 52 21

An olfactory cocktail party: figure-ground segregation of odorants in rodents.

PubMed

Rokni, Dan; Hemmelder, Vivian; Kapoor, Vikrant; Murthy, Venkatesh N

2014-09-01

In odorant-rich environments, animals must be able to detect specific odorants of interest against variable backgrounds. However, studies have found that both humans and rodents are poor at analyzing the components of odorant mixtures, suggesting that olfaction is a synthetic sense in which mixtures are perceived holistically. We found that mice could be easily trained to detect target odorants embedded in unpredictable and variable mixtures. To relate the behavioral performance to neural representation, we imaged the responses of olfactory bulb glomeruli to individual odors in mice expressing the Ca(2+) indicator GCaMP3 in olfactory receptor neurons. The difficulty of segregating the target from the background depended strongly on the extent of overlap between the glomerular responses to target and background odors. Our study indicates that the olfactory system has powerful analytic abilities that are constrained by the limits of combinatorial neural representation of odorants at the level of the olfactory receptors.

A pilot study on remediation of sediments enriched by oyster farming wastes using granulated coal ash.

PubMed

Yamamoto, T; Kim, K H; Shirono, K

2015-01-15

In order to evaluate the ability of granulated coal ash (GCA), a byproduct of coal thermal electric power stations, to remove hydrogen sulfide from organically enriched sediments, a pilot study was carried out at oyster farming sites, where sediments were enriched with oyster feces and dead oysters. Concentration of hydrogen sulfide in the interstitial water of the sediment decreased to nearly zero in both experimental sites, whereas it remained over 0.2mg/l in the control site. Concentration of acid volatile sulfide (AVS) in the sediment also decreased significantly in both experimental sites, while remained over 0.4 mg/g in the control site. Increases were observed in both the number of benthic microalgae species and the individual number of benthic animals in the surface sediments. This may have been due to the decrease in hydrogen sulfide. Copyright © 2014 Elsevier Ltd. All rights reserved.

Supercapacitors Based on Three-Dimensional Hierarchical Graphene Aerogels with Periodic Macropores.

PubMed

Zhu, Cheng; Liu, Tianyu; Qian, Fang; Han, T Yong-Jin; Duoss, Eric B; Kuntz, Joshua D; Spadaccini, Christopher M; Worsley, Marcus A; Li, Yat

2016-06-08

Graphene is an atomically thin, two-dimensional (2D) carbon material that offers a unique combination of low density, exceptional mechanical properties, thermal stability, large surface area, and excellent electrical conductivity. Recent progress has resulted in macro-assemblies of graphene, such as bulk graphene aerogels for a variety of applications. However, these three-dimensional (3D) graphenes exhibit physicochemical property attenuation compared to their 2D building blocks because of one-fold composition and tortuous, stochastic porous networks. These limitations can be offset by developing a graphene composite material with an engineered porous architecture. Here, we report the fabrication of 3D periodic graphene composite aerogel microlattices for supercapacitor applications, via a 3D printing technique known as direct-ink writing. The key factor in developing these novel aerogels is creating an extrudable graphene oxide-based composite ink and modifying the 3D printing method to accommodate aerogel processing. The 3D-printed graphene composite aerogel (3D-GCA) electrodes are lightweight, highly conductive, and exhibit excellent electrochemical properties. In particular, the supercapacitors using these 3D-GCA electrodes with thicknesses on the order of millimeters display exceptional capacitive retention (ca. 90% from 0.5 to 10 A·g(-1)) and power densities (>4 kW·kg(-1)) that equal or exceed those of reported devices made with electrodes 10-100 times thinner. This work provides an example of how 3D-printed materials, such as graphene aerogels, can significantly expand the design space for fabricating high-performance and fully integrable energy storage devices optimized for a broad range of applications.

Generation of a Homozygous Transgenic Rat Strain Stably Expressing a Calcium Sensor Protein for Direct Examination of Calcium Signaling

PubMed Central

Szebényi, Kornélia; Füredi, András; Kolacsek, Orsolya; Pergel, Enikő; Bősze, Zsuzsanna; Bender, Balázs; Vajdovich, Péter; Tóvári, József; Homolya, László; Szakács, Gergely; Héja, László; Enyedi, Ágnes; Sarkadi, Balázs; Apáti, Ágota; Orbán, Tamás I.

2015-01-01

In drug discovery, prediction of selectivity and toxicity require the evaluation of cellular calcium homeostasis. The rat is a preferred laboratory animal for pharmacology and toxicology studies, while currently no calcium indicator protein expressing rat model is available. We established a transgenic rat strain stably expressing the GCaMP2 fluorescent calcium sensor by a transposon-based methodology. Zygotes were co-injected with mRNA of transposase and a CAG-GCaMP2 expressing construct, and animals with one transgene copy were pre-selected by measuring fluorescence in blood cells. A homozygous rat strain was generated with high sensor protein expression in the heart, kidney, liver, and blood cells. No pathological alterations were found in these animals, and fluorescence measurements in cardiac tissue slices and primary cultures demonstrated the applicability of this system for studying calcium signaling. We show here that the GCaMP2 expressing rat cardiomyocytes allow the prediction of cardiotoxic drug side-effects, and provide evidence for the role of Na+/Ca2+ exchanger and its beneficial pharmacological modulation in cardiac reperfusion. Our data indicate that drug-induced alterations and pathological processes can be followed by using this rat model, suggesting that transgenic rats expressing a calcium-sensitive protein provide a valuable system for pharmacological and toxicological studies. PMID:26234466

Varicella Zoster Virus and Large Vessel Vasculitis, the Absence of an Association.

PubMed

Procop, Gary W; Eng, Charis; Clifford, Alison; Villa-Forte, Alexandra; Calabrese, Leonard H; Roselli, Eric; Svensson, Lars; Johnston, Douglas; Pettersson, Gosta; Soltesz, Edward; Lystad, Lisa; Perry, Julian D; Blandford, Alexander; Wilson, Deborah A; Hoffman, Gary S

2017-01-01

It is controversial whether microorganisms play a role in the pathogenesis of large and medium vessel vasculitides (eg, giant cell arteritis [GCA], Takayasu arteritis [TAK] and focal idiopathic aortitis [FIA]). Recent studies have reported the presence of Varicella Zoster Virus (VZV) within formalin-fixed, paraffin-embedded temporal arteries and aortas of about three-quarters or more of patients with these conditions, and in a minority of controls. In a prospective study, we sought to confirm these findings using DNA extracted from vessels that were harvested under surgically aseptic conditions and snap frozen. DNA samples extracted from 11 surgically sterile temporal arteries and 31 surgically sterile thoracic aortas were used in an attempt to identify the vessel-associated VZV genome. Two different validated PCR methods were used. Thirty-one thoracic aorta aneurysm specimens included biopsies from 8 patients with GCA, 2 from patients with TAK, 6 from patients with FIA, and 15 from patients without vasculitis, who had non-inflammatory aneurysms. Eleven temporal artery biopsies were collected from 5 patients with GCA and 6 controls. The presence of VZV was not identified in either the specimens from patients with large vessel vasculitis or from the controls. Using surgically sterile snap-frozen specimens, we were unable to confirm recent reports of the presence of VZV in either aortas or temporal arteries from patients with large vessel vasculitis or controls.

Varicella Zoster Virus and Large Vessel Vasculitis, the Absence of an Association

PubMed Central

Procop, Gary W.; Eng, Charis; Clifford, Alison; Villa-Forte, Alexandra; Calabrese, Leonard H.; Roselli, Eric; Svensson, Lars; Johnston, Douglas; Pettersson, Gosta; Soltesz, Edward; Lystad, Lisa; Perry, Julian D.; Blandford, Alexander; Wilson, Deborah A.; Hoffman, Gary S.

2017-01-01

Objective It is controversial whether microorganisms play a role in the pathogenesis of large and medium vessel vasculitides (eg, giant cell arteritis [GCA], Takayasu arteritis [TAK] and focal idiopathic aortitis [FIA]). Recent studies have reported the presence of Varicella Zoster Virus (VZV) within formalin-fixed, paraffin-embedded temporal arteries and aortas of about three-quarters or more of patients with these conditions, and in a minority of controls. In a prospective study, we sought to confirm these findings using DNA extracted from vessels that were harvested under surgically aseptic conditions and snap frozen. Methods and Results DNA samples extracted from 11 surgically sterile temporal arteries and 31 surgically sterile thoracic aortas were used in an attempt to identify the vessel-associated VZV genome. Two different validated PCR methods were used. Thirty-one thoracic aorta aneurysm specimens included biopsies from 8 patients with GCA, 2 from patients with TAK, 6 from patients with FIA, and 15 from patients without vasculitis, who had non-inflammatory aneurysms. Eleven temporal artery biopsies were collected from 5 patients with GCA and 6 controls. The presence of VZV was not identified in either the specimens from patients with large vessel vasculitis or from the controls. Conclusions Using surgically sterile snap-frozen specimens, we were unable to confirm recent reports of the presence of VZV in either aortas or temporal arteries from patients with large vessel vasculitis or controls. PMID:28758156

Comparison among the efficacy of interventions for the return rate to receive the pap test report: randomized controlled clinical trial.

PubMed

Vasconcelos, Camila Teixeira Moreira; Pinheiro, Ana Karina Bezerra; Nicolau, Ana Izabel Oliveira; Lima, Thaís Marques; Barbosa, Denise de Fátima Fernandes

2017-03-02

to test the effects of a behavioral, an educative and a comparative intervention on women's adherence to the return appointment to receive the pap test report. randomized controlled clinical trial at a Primary Health Care Service, involving three groups: EG (educative session and test demonstration), BG (recall ribbon) and standard intervention (card containing the return appointment - graphical reminder), called comparative group here (CG). To select the sample, the following was established: having started sexual activity and undergoing the pap smear during the study, resulting in 775 women. among the 775 women, 585 (75.5%) returned to receive the test result within 65 days. The educative group presented the highest return rate (EG=82%/CG=77%/BG=66%), statistically significant only when compared to the behavioral group (p=0.000). The educative group obtained the smallest interval (p<0.05) concerning the mean number of days of return to receive the test result (EG:M=43days/BG:M=47.5days/CG:M=44.8 days). the educative group reached higher return rates and the women returned earlier, but the behavioral intervention showed to be the least effective. Brazilian Clinical Trial Register: RBR-93ykhs. testar los efectos de una intervención comportamental (GCP), educativa (GE) y otra comparativa (GCA) en la adhesión de las mujeres a la consulta de retorno para recibir el laudo de citología vaginal. estudio experimental aleatorizado controlado en una Unidad de Atención Primaria de Salud con tres grupos: GE (sesión educativa y demonstración del examen), GCP (cinta recuerdo) e intervención estándar (tarjeta con la fecha de la consulta de retorno - recuerdo gráfico), llamado de grupo comparativo (GCA). Para seleccionar la muestra, fue establecido: haber iniciado actividad sexual y hacer la citología vaginal durante el estudio, resultando en 775 mujeres. entre las 775 mujeres, 585 (75,5%) regresaron para recibir el resultado del examen con hasta 65 días. El grupo educativo presentó el mayor porcentaje de retorno (GE=82%/GCA=77%/GCP=66%), con significancia estadística sólo cuando comparado al comportamental (p=0,000). El grupo educativo alcanzó menor intervalo (p<0,05) del promedio de días de retorno para recibir el resultado del examen (GE:M=43 días/GCP:M=47,5 días/GCA:M=44,8 días). el grupo educativo alcanzó proporciones mayores de retorno, y las mujeres regresaron más precozmente, pero la intervención comportamental se mostró la menos eficaz. Registro Brasileño de Ensayo Clínico: RBR-93ykhs. testar os efeitos de uma intervenção comportamental (GCP), educativa (GE) e outra de comparação (GCA) na adesão das mulheres à consulta de retorno para receber o laudo do exame colpocitológico. estudo experimental randomizado controlado em uma Unidade de Atenção Primária à Saúde com três grupos: GE (sessão educativa e demonstração do exame), GCP (fita lembrança) e intervenção-padrão (cartão contendo a data da consulta de retorno - lembrete gráfico), aqui denominado de grupo de comparação (GCA). Para a seleção da amostra, estabeleceu-se: ter iniciado atividade sexual e realizar o exame colpocitológico durante o estudo, resultando em 775 mulheres. dentre as 775 mulheres, 585 (75,5%) retornaram para receber, o resultado do exame com até 65 dias. O grupo educativo apresentou o maior percentual de retorno (GE=82%/GCA=77%/GCP=66%), com significância estatística apenas quando comparado ao comportamental (p=0,000). O grupo educativo obteve menor intervalo (p<0,05) da média de dias de retorno para receber o resultado do exame (GE:M=43dias/GCP:M=47,5dias/GCA:M=44,8 dias) . o grupo educativo atingiu proporções maiores de retorno, e as mulheres retornaram mais precocemente, porém a intervenção comportamental mostrou-se a menos eficaz. Registro Brasileiro de Ensaio Clínico: RBR-93ykhs.

A pooled analysis of dietary sugar/carbohydrate intake and esophageal and gastric cardia adenocarcinoma incidence and survival in the USA.

PubMed

Li, Nan; Petrick, Jessica L; Steck, Susan E; Bradshaw, Patrick T; McClain, Kathleen M; Niehoff, Nicole M; Engel, Lawrence S; Shaheen, Nicholas J; Risch, Harvey A; Vaughan, Thomas L; Wu, Anna H; Gammon, Marilie D

2017-12-01

During the past 40 years, esophageal/gastric cardia adenocarcinoma (EA/GCA) incidence increased in Westernized countries, but survival remained low. A parallel increase in sugar intake, which may facilitate carcinogenesis by promoting hyperglycaemia, led us to examine sugar/carbohydrate intake in association with EA/GCA incidence and survival. We pooled 500 EA cases, 529 GCA cases and 2027 controls from two US population-based case-control studies with cases followed for vital status. Dietary intake, assessed by study-specific food frequency questionnaires, was harmonized and pooled to estimate 12 measures of sugar/carbohydrate intake. Multivariable-adjusted odds ratios (ORs) and hazard ratios [95% confidence intervals (CIs)] were calculated using multinomial logistic regression and Cox proportional hazards regression, respectively. EA incidence was increased by 51-58% in association with sucrose (ORQ5vs.Q1 = 1.51, 95% CI = 1.01-2.27), sweetened desserts/beverages (ORQ5vs.Q1 = 1.55, 95% CI = 1.06-2.27) and the dietary glycaemic index (ORQ5vs.Q1 = 1.58, 95% CI = 1.13-2.21). Body mass index (BMI) and gastro-esophageal reflux disease (GERD) modified these associations (Pmultiplicative-interaction ≤ 0.05). For associations with sucrose and sweetened desserts/beverages, respectively, the OR was elevated for BMI < 25 (ORQ4-5vs.Q1-3 = 1.79, 95% CI = 1.26-2.56 and ORQ4-5vs.Q1-3 = 1.45, 95% CI = 1.03-2.06), but not BMI ≥ 25 (ORQ4-5vs.Q1-3 = 1.05, 95% CI = 0.76-1.44 and ORQ4-5vs.Q1-3 = 0.85, 95% CI = 0.62-1.16). The EA-glycaemic index association was elevated for BMI ≥ 25 (ORQ4-5vs.Q1-3 = 1.38, 95% CI = 1.03-1.85), but not BMI < 25 (ORQ4-5vs.Q1-3 = 0.88, 95% CI = 0.62-1.24). The sucrose-EA association OR for GERD < weekly was 1.58 (95% CI = 1.16-2.14), but for GERD ≥ weekly was 1.01 (95% CI = 0.70-1.47). Sugar/carbohydrate measures were not associated with GCA incidence or EA/GCA survival. If confirmed, limiting intake of sucrose (e.g. table sugar), sweetened desserts/beverages, and foods that contribute to a high glycaemic index, may be plausible EA risk reduction strategies. Published by Oxford University Press on behalf of the International Epidemiological Association 2017. This work is written by US Government employees and is in the public domain in the United States.

Secondary overprinting of S-Se-Te signatures in the Earth's mantle: Implications for the Late Veneer

NASA Astrophysics Data System (ADS)

Koenig, S.; Luguet, A.; Lorand, J.; Pearson, D.

2013-12-01

Sulphur, Selenium and Tellurium are both chalcophile and highly siderophile elements (HSE) with near-chondritic ratios and absolute abundances in the terrestrial mantle that exceed those predicted by core-mantle differentiation[1]. These 'excess' HSE abundances have been attributed to addition of ca. 0.5% of chondrite-like material that hit the Earth in its accretionary stage between 4 to 3.8 billion years ago after core-mantle differentiation (Late Veneer[2]). Therefore, like other HSE, S, Se and Te are considered potential tracers for the composition of the Late Veneer, provided that their bulk silicate Earth abundances are properly constrained. In contrast to ca. 250 ppm S, Se and Te are ultra-trace elements in the terrestrial mantle. Like all HSE, they are furthermore controlled by base metal sulphides (BMS) and micrometric platinum group minerals (PGMs)[3]. This strong control exerted by the host mineralogy and petrology on the S-Se-Te systematics at both the micro-scale and the whole-rock scale makes detailed mineralogical and petrological studies of BMS and PGM a pre-requisite to fully understand and accurately interpret the whole-rock signatures. Here we combine in-situ sulphide data and detailed mineralogical observations with whole-rock S-Se-Te-HSE signatures of both lherzolites and harburgites from different geodynamic settings. We demonstrate that the near-chondritic Se and Te signature of 'fertile' mantle rocks (Se/Te ≈9×5) is not a primitive signature of the Earth's mantle, but rather reflects strong enrichment in metasomatic HSE host phases, which erased previous pristine signatures. Consequently, current attempts to identify a potential Late Veneer composition are seriously flawed because, neither refertilisation/metasomatism nor true melt depletion (e.g. harzburgitic residues) have been taken into account for the Primitive Upper Mantle composition estimate[4]. Our combined whole rock and in-situ sulphide data indicate a refertilisation trend towards sub-chondritic Se/Te ratios (i.e. Se/Te < 2). On the other hand, harzburgites that preserve depletion signatures show suprachondritic Se/Te ratios (< 31). Altogether this shows that metasomatic enrichment of mantle rocks may lead to a systematic bias and hence underestimation of the current Se/Te estimate of the primitive mantle. The metasomatic origin of the reported S, Se and Te ratios in peridotites that reflect the control of metasomatic BMS and PGMs[5;6] furthermore show that not all whole rock signatures in the Earth's mantle that scatter around near-chondritic values are primary and hence challenge the simple conception that these features may readily solve the long-standing conundrum of the Late Veneer composition. Refs: [1] Rose-Weston et al. (2009) GCA 73, 4598-4615; [2] Kimura et al. (1974) GCA 38, 683-701; [3] Lorand and Alard (2010) 67, 4137-4151; [4] Wang and Becker (2013) Nature 499, 328-331; [5] König et al. (2012) GCA 86, 354-366; [6] König et al. (2013, in press), EPSL.

Organic Molecules in Meteorites

NASA Astrophysics Data System (ADS)

Martins, Zita

2015-08-01

Carbonaceous meteorites are primitive samples from the asteroid belt, containing 3-5wt% organic carbon. The exogenous delivery of organic matter by carbonaceous meteorites may have contributed to the organic inventory of the early Earth. The majority (>70%) of the meteoritic organic material consist of insoluble organic matter (IOM) [1]. The remaining meteoritic organic material (<30%) consists of a rich organic inventory of soluble organic compounds, including key compounds important in terrestrial biochemistry [2-4]. Different carbonaceous meteorites contain soluble organic molecules with different abundances and distributions, which may reflect the extension of aqueous alteration or thermal metamorphism on the meteorite parent bodies. Extensive aqueous alteration on the meteorite parent body may result on 1) the decomposition of α-amino acids [5, 6]; 2) synthesis of β- and γ-amino acids [2, 6-9]; 3) higher relative abundances of alkylated polycyclic aromatic hydrocarbons (PAHs) [6, 10]; and 4) higher L-enantiomer excess (Lee) value of isovaline [6, 11, 12].The soluble organic content of carbonaceous meteorites may also have a contribution from Fischer-Tropsch/Haber-Bosch type gas-grain reactions after the meteorite parent body cooled to lower temperatures [13, 14].The analysis of the abundances and distribution of the organic molecules present in meteorites helps to determine the physical and chemical conditions of the early solar system, and the prebiotic organic compounds available on the early Earth.[1] Cody and Alexander (2005) GCA 69, 1085. [2] Cronin and Chang (1993) in: The Chemistry of Life’s Origin. pp. 209-258. [3] Martins and Sephton (2009) in: Amino acids, peptides and proteins in organic chemistry. pp. 1-42. [4] Martins (2011) Elements 7, 35. [5] Botta et al. (2007) MAPS 42, 81. [6] Martins et al. (2015) MAPS, in press. [7] Cooper and Cronin (1995) GCA 59, 1003. [8] Glavin et al. (2006) MAPS. 41, 889. [9] Glavin et al. (2011) MAPS 45, 1948. [10] Elsila et al. (2005) GCA 5, 1349. [11] Glavin and Dworkin (2009) PNAS 106, 5487. [12] Pizzarello et al. (2003) GCA 67, 1589. [13] Chan et al. (2012) MAPS. 47, 1502. [14] Burton et al. (2011) MAPS 46, 1703.

Risk Associated with Cumulative Oral Glucocorticoid Use in Patients with Giant Cell Arteritis in Real-World Databases from the USA and UK.

PubMed

Gale, Sara; Wilson, Jessica C; Chia, Jenny; Trinh, Huong; Tuckwell, Katie; Collinson, Neil; Dimonaco, Sophie; Jick, Susan; Meier, Christoph; Mohan, Shalini V; Sarsour, Khaled

2018-05-11

Treatment of giant cell arteritis (GCA) involves immediate initiation of high-dose glucocorticoid therapy with slow tapering of the dose over many months. Chronic exposure to glucocorticoids is associated with serious comorbidities. The objective of this analysis was to determine the glucocorticoid exposure and risk of glucocorticoid-related adverse events (AEs) in real-world patients with GCA. Data from the Truven Healthcare MarketScan ® database (from January 1, 2000, to June 30, 2015) and the Clinical Practice Research Datalink (CPRD; from January 1, 1995, to August 31, 2013) were used to retrospectively analyze patients aged ≥ 50 years with GCA in the USA and UK, respectively. Outcomes included oral glucocorticoid use (cumulative prednisone-equivalent exposure), glucocorticoid-related AEs and the association of AE risk with glucocorticoid exposure over 52 weeks. Of the 4804 patients in the US MarketScan database and 3973 patients in the UK CPRD database included, 71.3 and 74.6% were women and mean age was 73.4 and 73.0 years, respectively. Median starting glucocorticoid dose and cumulative glucocorticoid dose at 52 weeks were 20-50 mg/day and 4000-4800 mg, respectively. The most frequent glucocorticoid-related AEs were hypertension and eye, bone health, and glucose tolerance conditions. In the first year after diagnosis, the likelihood of any glucocorticoid-related AE was significantly increased for each 1 g increase in cumulative glucocorticoid dose in the US and UK cohorts (odds ratio [95% CI], 1.170 [1.063, 1.287] and 1.06 [1.03, 1.09], respectively; P < 0.05 for both). Similar trends were observed for the risk of glucocorticoid-related AEs over full follow-up (mean, USA: 3.9 years, UK: 6.3 years). In real-world patients with GCA, increased cumulative glucocorticoid exposure was associated with an increased risk of glucocorticoid-related AEs. F. Hoffmann-La Roche Ltd. Plain language summary available for this article.

Giant cell angiofibroma of the scalp: A benign rare neoplasm with bone destruction

PubMed Central

Arifin, Muhammad Z.; Tjahjono, Firman P.; Faried, Ahmad; Gill, Arwinder S.; Cahyadi, Alexander; Hernowo, Bethy S.

2013-01-01

Background: The incidence of extraorbital giant cell angiofibroma (GCA) is rare, with only one case located in the scalp reported in the literature. The morphological hallmark is histopathological examination showing richly vascularized pattern-less spindle cell proliferation containing pseudovascular spaces and floret-like multinucleate giant cells. Case Description: We report a case of a 30-year-old female with a primary complaint of a painless solitary nodule arising on the left parietal region of the scalp. Complete tumor removal through surgical intervention was achieved, and the postoperative period was uneventful. Conclusion: Diagnosing a highly vascularized tumor in the head and neck is challenging. Our case is unique in that it is presented as a GCA of the scalp, which is an extremely rare clinical entity, and also demonstrated bone destruction. PMID:24231802

The three subtypes of atrial natriuretic peptide (ANP) receptors are expressed in the rat adrenal gland.

PubMed

Grandclément, B; Ronsin, B; Morel, G

1997-03-01

Atrial natriuretic peptide (ANP) actions are mediated by highly selective and specific receptors. Three subtypes have been characterized and cloned: ANP receptor-A (or GC-A), -B (or GC-B) and -C (the so-called clearance receptor). In rat adrenal gland, the mRNA for each subtype was detected using 35S-dUTP or digoxigenin-11-dUTP specific labeled probes, and in situ hybridization at light and electron microscopic levels respectively. The three subtypes were expressed the most abundantly in the zona glomerulosa. The amount of GC-A mRNA expression, quantified using macro-autoradiography and densitometry, was higher than the amounts of GC-B mRNA and ANPR-C mRNA both in zona glomerulosa and medullary of adrenal gland. At electron microscopic level, the three subtypes of ANPR were revealed in glomerulosa cells. A noticeable signal was also present in the medullary area, especially for GC-A mRNA, in adrenaline-containing chromaffin cells. No signal was detected in noradrenaline-containing chromaffin cells. The subcellular localization of the three mRNAs is similar: in the cytoplasmic matrix and in the euchromatin of the nucleus in each cell of glomerulosa, and in the same compartments of the adrenaline-containing chromaffin cells. These data indicate that the adrenal gland is an important target tissue for ANP action both in glomerulosa cells and adrenaline-containing chromaffin cells. The mRNA expression levels were different for each ANPR subtype.

In vivo neuronal calcium imaging in C. elegans.

PubMed

Chung, Samuel H; Sun, Lin; Gabel, Christopher V

2013-04-10

The nematode worm C. elegans is an ideal model organism for relatively simple, low cost neuronal imaging in vivo. Its small transparent body and simple, well-characterized nervous system allows identification and fluorescence imaging of any neuron within the intact animal. Simple immobilization techniques with minimal impact on the animal's physiology allow extended time-lapse imaging. The development of genetically-encoded calcium sensitive fluorophores such as cameleon and GCaMP allow in vivo imaging of neuronal calcium relating both cell physiology and neuronal activity. Numerous transgenic strains expressing these fluorophores in specific neurons are readily available or can be constructed using well-established techniques. Here, we describe detailed procedures for measuring calcium dynamics within a single neuron in vivo using both GCaMP and cameleon. We discuss advantages and disadvantages of both as well as various methods of sample preparation (animal immobilization) and image analysis. Finally, we present results from two experiments: 1) Using GCaMP to measure the sensory response of a specific neuron to an external electrical field and 2) Using cameleon to measure the physiological calcium response of a neuron to traumatic laser damage. Calcium imaging techniques such as these are used extensively in C. elegans and have been extended to measurements in freely moving animals, multiple neurons simultaneously and comparison across genetic backgrounds. C. elegans presents a robust and flexible system for in vivo neuronal imaging with advantages over other model systems in technical simplicity and cost.

FDG-PET/CT(A) imaging in large vessel vasculitis and polymyalgia rheumatica: joint procedural recommendation of the EANM, SNMMI, and the PET Interest Group (PIG), and endorsed by the ASNC.

PubMed

Slart, Riemer H J A

2018-07-01

Large vessel vasculitis (LVV) is defined as a disease mainly affecting the large arteries, with two major variants, Takayasu arteritis (TA) and giant cell arteritis (GCA). GCA often coexists with polymyalgia rheumatica (PMR) in the same patient, since both belong to the same disease spectrum. FDG-PET/CT is a functional imaging technique which is an established tool in oncology, and has also demonstrated a role in the field of inflammatory diseases. Functional FDG-PET combined with anatomical CT angiography, FDG-PET/CT(A), may be of synergistic value for optimal diagnosis, monitoring of disease activity, and evaluating damage progression in LVV. There are currently no guidelines regarding PET imaging acquisition for LVV and PMR, even though standardization is of the utmost importance in order to facilitate clinical studies and for daily clinical practice. This work constitutes a joint procedural recommendation on FDG-PET/CT(A) imaging in large vessel vasculitis (LVV) and PMR from the Cardiovascular and Inflammation & Infection Committees of the European Association of Nuclear Medicine (EANM), the Cardiovascular Council of the Society of Nuclear Medicine and Molecular Imaging (SNMMI), and the PET Interest Group (PIG), and endorsed by the American Society of Nuclear Cardiology (ASNC). The aim of this joint paper is to provide recommendations and statements, based on the available evidence in the literature and consensus of experts in the field, for patient preparation, and FDG-PET/CT(A) acquisition and interpretation for the diagnosis and follow-up of patients with suspected or diagnosed LVV and/or PMR. This position paper aims to set an internationally accepted standard for FDG-PET/CT(A) imaging and reporting of LVV and PMR.

Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics

PubMed Central

Akerboom, Jasper; Carreras Calderón, Nicole; Tian, Lin; Wabnig, Sebastian; Prigge, Matthias; Tolö, Johan; Gordus, Andrew; Orger, Michael B.; Severi, Kristen E.; Macklin, John J.; Patel, Ronak; Pulver, Stefan R.; Wardill, Trevor J.; Fischer, Elisabeth; Schüler, Christina; Chen, Tsai-Wen; Sarkisyan, Karen S.; Marvin, Jonathan S.; Bargmann, Cornelia I.; Kim, Douglas S.; Kügler, Sebastian; Lagnado, Leon; Hegemann, Peter; Gottschalk, Alexander; Schreiter, Eric R.; Looger, Loren L.

2013-01-01

Genetically encoded calcium indicators (GECIs) are powerful tools for systems neuroscience. Here we describe red, single-wavelength GECIs, “RCaMPs,” engineered from circular permutation of the thermostable red fluorescent protein mRuby. High-resolution crystal structures of mRuby, the red sensor RCaMP, and the recently published red GECI R-GECO1 give insight into the chromophore environments of the Ca2+-bound state of the sensors and the engineered protein domain interfaces of the different indicators. We characterized the biophysical properties and performance of RCaMP sensors in vitro and in vivo in Caenorhabditis elegans, Drosophila larvae, and larval zebrafish. Further, we demonstrate 2-color calcium imaging both within the same cell (registering mitochondrial and somatic [Ca2+]) and between two populations of cells: neurons and astrocytes. Finally, we perform integrated optogenetics experiments, wherein neural activation via channelrhodopsin-2 (ChR2) or a red-shifted variant, and activity imaging via RCaMP or GCaMP, are conducted simultaneously, with the ChR2/RCaMP pair providing independently addressable spectral channels. Using this paradigm, we measure calcium responses of naturalistic and ChR2-evoked muscle contractions in vivo in crawling C. elegans. We systematically compare the RCaMP sensors to R-GECO1, in terms of action potential-evoked fluorescence increases in neurons, photobleaching, and photoswitching. R-GECO1 displays higher Ca2+ affinity and larger dynamic range than RCaMP, but exhibits significant photoactivation with blue and green light, suggesting that integrated channelrhodopsin-based optogenetics using R-GECO1 may be subject to artifact. Finally, we create and test blue, cyan, and yellow variants engineered from GCaMP by rational design. This engineered set of chromatic variants facilitates new experiments in functional imaging and optogenetics. PMID:23459413

The neurobiological drive for overeating implicated in Prader-Willi syndrome.

PubMed

Zhang, Yi; Wang, Jing; Zhang, Guansheng; Zhu, Qiang; Cai, Weiwei; Tian, Jie; Zhang, Yi Edi; Miller, Jennifer L; Wen, Xiaotong; Ding, Mingzhou; Gold, Mark S; Liu, Yijun

2015-09-16

Prader-Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous fMRI studies examined the activation of eating-related neural circuits in PWS patients with or without exposures to food cues and found an excessive eating motivation and a reduced inhibitory control of cognitive processing of food. However, the effective connectivity between various brain areas or neural circuitry critically implicated in both the biological and behavioral control of overeating in PWS is largely unexplored. The current study combined resting-state fMRI and Granger causality analysis (GCA) techniques to investigate interactive causal influences among key neural pathways underlying overeating in PWS. We first defined the regions of interest (ROIs) that demonstrated significant alterations of the baseline brain activity levels in children with PWS (n = 21) as compared to that of their normal siblings controls (n = 18), and then carried out GCA to characterize the region-to-region interactions among these ROIs. Our data revealed significantly enhanced causal influences from the amygdala to the hypothalamus and from both the medial prefrontal cortex and anterior cingulate cortex to the amygdala in patients with PWS (P < 0.001). These alterations offer new explanations for hypothalamic regulation of homeostatic energy intake and impairment in inhibitory control circuit. The deficits in these dual aspects may jointly contribute to the extreme hyperphagia in PWS. This study provides both a new methodological and a neurobiological perspective to aid in a better understanding of neural mechanisms underlying obesity in the general public. This article is part of a Special Issue entitled 1618. Copyright © 2015 Elsevier B.V. All rights reserved.

Establishing the solubility and local structure(s) of Amorphous Calcium Carbonate (ACC): Toward an understanding of invertebrate biomineralization

NASA Astrophysics Data System (ADS)

Mergelsberg, S. T.; Ulrich, R. N.; Michel, F. M.; Dove, P. M.

2017-12-01

Recent advances in high-resolution imaging show the widespreadd occurrence of multistep pathways to mineralization in biological and geological settings (De Yoreo et al., 2015, Science). For example, carbonate biomineralization often involves precipitation of amorphous calcium carbonate (ACC) as a reactive intermediate that subsequently transforms to crystalline products with diverse structures. Although current carbonate mineral proxies are based upon the composition of final crystalline products, the final signatures may be recording the properties of the initial amorphous phase. Thus, it is critical to establish the physical properties of ACC and understand the factors that influence its evolution to final products at conditions that approximate biological environments. This disconnect limits our ability to build a process-based understanding of when/how minor and trace elements are recorded in mineral composition proxies. In this experimental study, we quantified the chemical and physical properties of ACC and its evolution to final products. We first determined ACC solubility under controlled chemical conditions using a new type of flow-through reactor developed by our research group (Blue and Dove, 2015, GCA; Blue et al., 2017, GCA). The experimental design varied Mg concentration and total alkalinity while maintaining a mild pH that approximates biological environments. ACC solubility was measured at specific time points during the precipitation (from super- and undersaturated conditions) and during its subsequent evolution. Parallel experiments characterized the structure of the corresponding amorphous products using in situ pair distribution function (PDF) and small-angle x-ray scattering (SAXS) analyses. The measurements demonstrate at least two types of ACC can be produced by tuning Mg concentration and alkalinity. Each "phase" exhibits distinct short-range ordering that demonstrates structure-specific solubility. We also find temporal changes in the short-range order of each type of ACC that are dependent upon Mg content. Insights from this study hold promise for quantifying the chemical and structural properties of ACC and reconcile discrepancies in the literature.

77 FR 37920 - Agency Information Collection Activities; Proposed Collection; Comments Requested: Firearms...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-25

... other technological collection techniques or other forms of information technology, e.g., permitting...-profit. Need for Collection The form is used to determine the eligibility, under the Gun Control Act (GCA...

77 FR 51576 - Agency Information Collection Activities; Proposed Collection; Comments Request: Firearms...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-24

... techniques or other forms of information technology, e.g., permitting electronic submission of responses... used to determine the eligibility, under the Gun Control Act (GCA), of a person to receive a firearm...

ENVIRONMENTAL APPLICATION OF GAS CHROMATOGRAPHY/ATOMIC EMISSION DETECTION

EPA Science Inventory

A gas chromatography/atomic emission detector (GC/AED) system has been evaluated for its applicability to environmental analysis. Detection limits, elemental response factors, and regression analysis data were determined for 58 semivolatile environmental contaminants. Detection l...

Initial value sensitivity of the Chinese stock market and its relationship with the investment psychology

NASA Astrophysics Data System (ADS)

Ying, Shangjun; Li, Xiaojun; Zhong, Xiuqin

2015-04-01

This paper discusses the initial value sensitivity (IVS) of Chinese stock market, including the single stock market and the Chinese A-share stock market, with respect to real markets and evolving models. The aim is to explore the relationship between IVS of the Chinese A-share stock market and the investment psychology based on the evolving model of genetic cellular automaton (GCA). We find: (1) The Chinese stock market is sensitively dependent on the initial conditions. (2) The GCA model provides a considerable reliability in complexity simulation (e.g. the IVS). (3) The IVS of stock market is positively correlated with the imitation probability when the intensity of the imitation psychology reaches a certain threshold. The paper suggests that the government should seek to keep the imitation psychology under a certain level, otherwise it may induce severe fluctuation to the market.

Genotype x environment interaction and its implication in identification of common bean populations with high calcium content.

PubMed

Fernandes, S B; Abreu, A F B; Ramalho, M A P

2016-06-24

The common bean is a food with high mineral content. Of the various types of beans cultivated in Brazil, carioca type beans are the most consumed. The aim of this study was to identify promising common bean populations with an emphasis toward the selection of carioca type bean lines with high calcium content. We also aimed to verify whether and how the crop season and the genotype (parental line and hybrid populations) x crop season interaction affect calcium content. A group of 3 lines of good agronomic characteristics were crossed with a group of 4 lines with high calcium content in a 3 x 4 partial diallel design. Great variability was identified among both the parental lines and the hybrid populations derived from the diallel crosses among the parental lines. We found significant interactions between crop season and both parental line and hybrid population. In the diallel analysis, only the general combining ability was significant, explaining 89.4% of the sum of squares. The RP-1, CNF05, and Safira lines exhibited the greatest calcium contents and a positive GCA. RP-1 is a line that presents high calcium content, in addition to having carioca type beans and an upright plant with high yield. To further increase the calcium content of the RP-1 line, we suggest crossing it with the CNF05 and Safira lines. Although there was a hybrid population x crop season interaction, it was possible to identify populations that performed best in terms of calcium content in both crop seasons.

Development of a Core Set of Outcome Measures for Large-vessel Vasculitis: Report from OMERACT 2016.

PubMed

Sreih, Antoine G; Alibaz-Oner, Fatma; Kermani, Tanaz A; Aydin, Sibel Z; Cronholm, Peter F; Davis, Trocon; Easley, Ebony; Gul, Ahmet; Mahr, Alfred; McAlear, Carol A; Milman, Nataliya; Robson, Joanna C; Tomasson, Gunnar; Direskeneli, Haner; Merkel, Peter A

2017-12-01

Among the challenges in conducting clinical trials in large-vessel vasculitis (LVV), including both giant cell arteritis (GCA) and Takayasu arteritis (TA), is the lack of standardized and meaningful outcome measures. The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group initiated an international effort to develop and validate data-driven outcome tools for clinical investigation in LVV. An international Delphi exercise was completed to gather opinions from clinical experts on LVV-related domains considered important to measure in trials. Patient interviews and focus groups were completed to identify outcomes of importance to patients. The results of these activities were presented and discussed in a "Virtual Special Interest Group" using telephone- and Internet-based conferences, discussions through electronic mail, and an in-person session at the 2016 OMERACT meeting. A preliminary core set of domains common for all forms of LVV with disease-specific elements was proposed. The majority of experts agree with using common outcome measures for GCA and TA, with the option of supplementation with disease-specific items. Following interviews and focus groups, pain, fatigue, and emotional effect emerged as health-related quality of life domains important to patients. Current disease assessment tools, including the Birmingham Vasculitis Activity Score, were found to be inadequate to assess disease activity in GCA and standardized assessment of imaging tests were felt crucial to study LVV, especially TA. Initial data from a clinician Delphi exercise and structured patient interviews have provided themes toward an OMERACT-endorsed core set of domains and outcome measures.

Karyotype evolution of giraffes (Giraffa camelopardalis) revealed by cross-species chromosome painting with Chinese muntjac (Muntiacus reevesi) and human (Homo sapiens) paints.

PubMed

Huang, L; Nesterenko, A; Nie, W; Wang, J; Su, W; Graphodatsky, A S; Yang, F

2008-01-01

Considering the giraffe (Giraffa camelopardalis, GCA, 2n = 30) as a primitive species, its comparative genomic data are critical for our understanding of the karyotype evolution of pecorans. Here, we have established genome-wide chromosomal homologies between giraffe, Chinese muntjac (Muntiacus reevesi, MRE, 2n = 46) and human (Homo sapiens, HSA, 2n = 46) with whole sets of chromosome-specific paints from Chinese muntjac and human, in addition to providing a high-resolution G-banding karyotype of giraffe. Chinese muntjac and human chromosome paints detected 32 and 45 autosomal homologs in the genome of giraffe, respectively. Our results suggest that it would require at least thirteen fissions, six fusions and three intrachromosomal rearrangements to 'transform' the 2n = 44 eutherian ancestral karyotype to the 2n = 58 pecoran ancestral karyotype. During giraffe evolution, some ancestral eutherian syntenies (i.e. association of HSA3/21, 4/8, 7/16, 14/15, 16/19 and two forms of 12/22) have been retained, while several derived syntenies (i.e. associations of human homologous segments 2/1, 2/9, 5/19, 4/12/22, 8/9, and 10/20) have been produced. The reduction of chromosome number in giraffe from the 2n = 58 pecoran ancestral karyotype could be primarily attributed to extensive Robertsonian translocations of ancestral chromosomal segments. More complex chromosomal rearrangements (including tandem fusion, centromere repositioning and pericentric inversion) have happened during the evolution of GCA2 and GCA8. Copyright 2008 S. Karger AG, Basel.

The effects of oxygen scavenging on jet fuel thermal stability

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

Heneghan, S.P.; Williams, T.F.; Whitacre, S.

1996-10-01

Preliminary tests with a proposed oxygen scavenger (triphenyl-phosphine, TPP) have been done in closed static and flowing systems to study its effects on the oxidation and the deposit formation of jet fuel. TPP was found to significantly slow the oxidation of hexadecane or jet fuel at some temperatures/concentrations and increase the oxidation rate at other conditions. The additive helped decrease the formation of deposits at higher concentrations (200 mg/l) but not at lower concentrations. No evidence of phosphorous was observed in the deposits that were formed. Gas chomatography combined with mass spectrometry and atomic emission detection showed that TPP producedmore » the expected oxidation product (triphenylphosphineoxide) and an unexpected triphenylphosphine-sulfide. The GC/AED allowed A quantitative analysis of the conversion efficiency of TPP to TPPO upon stressing in a closed system.« less

LOVE CANAL MONITORING PROGRAM. VOLUME 1

EPA Science Inventory

This report summarizes the prime contractor activities during the monitoring phase of the Love Canal project. Since GCA Corporation was only responsible for data collection, no analytical results appear in this report. The program involved a multifaceted sampling and analytical e...

32 CFR 806.5 - Responsibilities.

Code of Federal Regulations, 2011 CFR

2011-07-01

... instructions to MAJCOMs. Responsibilities of other Air Force elements follow. (b) SAF/GCA makes final decisions on FOIA administrative appeals. (c) Installation commanders will: Comply with FOIA electronic reading... commanders implement this instruction and appoint a FOIA manager, in writing. Send the name, phone number...

Dedication to Professor Hazel Prichard BSc, PhD, MBA (1954-2017)

NASA Astrophysics Data System (ADS)

Hall, Ian; Maier, Wolfgang; Barnes, Stephen J.

2017-11-01

The final section of this special issue of GCA on highly siderophile elements is dedicated to Professor Hazel Prichard (see Fig. 1) who sadly passed away in Cardiff on 1st January, 2017, after a brave battle with cancer.

FABRIC FILTER MODEL SENSITIVITY ANALYSIS

EPA Science Inventory

The report gives results of a series of sensitivity tests of a GCA fabric filter model, as a precursor to further laboratory and/or field tests. Preliminary tests had shown good agreement with field data. However, the apparent agreement between predicted and actual values was bas...

76 FR 80404 - Agency Information Collection Activities; Proposed Collection: Emergency Request for Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-23

... concluded that two existing applications of the Gun Control Act (GCA) by ATF impose restrictions upon the... Collection The form is used to determine the eligibility, under the Gun Control Act, of a person to receive a...

32 CFR 806.5 - Responsibilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... to the Director, Freedom of Information and Security Review (DFOISR), and provides guidance and instructions to MAJCOMs. Responsibilities of other Air Force elements follow. (b) SAF/GCA makes final decisions... Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION AIR FORCE FREEDOM OF...

GCaMP expression in retinal ganglion cells characterized using a low-cost fundus imaging system

NASA Astrophysics Data System (ADS)

Chang, Yao-Chuan; Walston, Steven T.; Chow, Robert H.; Weiland, James D.

2017-10-01

Objective. Virus-transduced, intracellular-calcium indicators are effective reporters of neural activity, offering the advantage of cell-specific labeling. Due to the existence of an optimal time window for the expression of calcium indicators, a suitable tool for tracking GECI expression in vivo following transduction is highly desirable. Approach. We developed a noninvasive imaging approach based on a custom-modified, low-cost fundus viewing system that allowed us to monitor and characterize in vivo bright-field and fluorescence images of the mouse retina. AAV2-CAG-GCaMP6f was injected into a mouse eye. The fundus imaging system was used to measure fluorescence at several time points post injection. At defined time points, we prepared wholemount retina mounted on a transparent multielectrode array and used calcium imaging to evaluate the responsiveness of retinal ganglion cells (RGCs) to external electrical stimulation. Main results. The noninvasive fundus imaging system clearly resolves individual (RGCs and axons. RGC fluorescence intensity and the number of observable fluorescent cells show a similar rising trend from week 1 to week 3 after viral injection, indicating a consistent increase of GCaMP6f expression. Analysis of the in vivo fluorescence intensity trend and in vitro neurophysiological responsiveness shows that the slope of intensity versus days post injection can be used to estimate the optimal time for calcium imaging of RGCs in response to external electrical stimulation. Significance. The proposed fundus imaging system enables high-resolution digital fundus imaging in the mouse eye, based on off-the-shelf components. The long-term tracking experiment with in vitro calcium imaging validation demonstrates the system can serve as a powerful tool monitoring the level of genetically-encoded calcium indicator expression, further determining the optimal time window for following experiment.

Revisited HLA and non-HLA genetics of Takayasu arteritis--where are we?

PubMed

Terao, Chikashi

2016-01-01

Takayasu arteritis (TAK) is an immune-mediated vasculitis affecting large arteries first reported in 1908 from Japan. Case reports of familial onset of TAK from Japan and other countries indicated genetic contribution to TAK onset beyond ethnicity. Genetic studies of TAK have been performed mainly addressing the human leukocyte antigen (HLA) locus. HLA genetic studies of TAK that have previously been reported are reviewed in this manuscript. HLA-B*52:01 is associated with TAK beyond population. Many of the associations other than HLA-B*52:01 can be explained by a haplotype with HLA-B*52:01. HLA-B*67:01 is a novel susceptibility HLA-B allele to TAK confirmed in the Japanese population. Further independent associations are suggested in the HLA locus. Involvement of the 171st and 67th amino acid residues with TAK onset has been indicated. The 67th amino acid may explain the difference in susceptibility effects to TAK and Behçet's disease between HLA-B*52:01 and *51:01. HLA-B*52:01 is associated not only with TAK susceptibility but also with clinical phenotypes. Recent genome-wide association studies of TAK revealed multiple non-HLA susceptibility genes. In particular, the IL12B region seems to have a central role in TAK onset and its progression. Whether TAK and giant cell arteritis (GCA), the other vasculitis affecting large arteries, are the same disease is an interesting question to address in spite of different clinical manifestations between the two diseases. GCA is associated with HLA-DR4, which is not associated with TAK. GCA is not associated with HLA-Bw52. These two diseases seem not to share non-HLA susceptibility loci based on the recent genetic studies.

Stimulation of feeding by three different glucose-sensing mechanisms requires hindbrain catecholamine neurons.

PubMed

Li, Ai-Jun; Wang, Qing; Dinh, Thu T; Powers, Bethany R; Ritter, Sue

2014-02-15

Previous work has shown that hindbrain catecholamine neurons are required components of the brain's glucoregulatory circuitry. However, the mechanisms and circuitry underlying their glucoregulatory functions are poorly understood. Here we examined three drugs, glucosamine (GcA), phloridzin (Phl) and 5-thio-d-glucose (5TG), that stimulate food intake but interfere in different ways with cellular glucose utilization or transport. We examined feeding and blood glucose responses to each drug in male rats previously injected into the hypothalamic paraventricular nucleus with anti-dopamine-β-hydroxylase conjugated to saporin (DSAP), a retrogradely transported immunotoxin that selectively lesions noradrenergic and adrenergic neurons, or with unconjugated saporin (SAP) control. Our major findings were 1) that GcA, Phl, and 5TG all stimulated feeding in SAP controls whether injected into the lateral or fourth ventricle (LV or 4V), 2) that each drug's potency was similar for both LV and 4V injections, 3) that neither LV or 4V injection of these drugs evoked feeding in DSAP-lesioned rats, and 4) that only 5TG, which blocks glycolysis, stimulated a blood glucose response. The antagonist of the MEK/ERK signaling cascade, U0126, attenuated GcA-induced feeding, but not Phl- or 5TG-induced feeding. Thus GcA, Phl, and 5TG, although differing in mechanism and possibly activating different neural populations, stimulate feeding in a catecholamine-dependent manner. Although results do not exclude the possibility that catecholamine neurons possess glucose-sensing mechanisms responsive to all of these agents, currently available evidence favors the possibility that the feeding effects result from convergent neural circuits in which catecholamine neurons are a required component.

Stimulation of feeding by three different glucose-sensing mechanisms requires hindbrain catecholamine neurons

PubMed Central

Wang, Qing; Dinh, Thu T.; Powers, Bethany R.; Ritter, Sue

2013-01-01

Previous work has shown that hindbrain catecholamine neurons are required components of the brain's glucoregulatory circuitry. However, the mechanisms and circuitry underlying their glucoregulatory functions are poorly understood. Here we examined three drugs, glucosamine (GcA), phloridzin (Phl) and 5-thio-d-glucose (5TG), that stimulate food intake but interfere in different ways with cellular glucose utilization or transport. We examined feeding and blood glucose responses to each drug in male rats previously injected into the hypothalamic paraventricular nucleus with anti-dopamine-β-hydroxylase conjugated to saporin (DSAP), a retrogradely transported immunotoxin that selectively lesions noradrenergic and adrenergic neurons, or with unconjugated saporin (SAP) control. Our major findings were 1) that GcA, Phl, and 5TG all stimulated feeding in SAP controls whether injected into the lateral or fourth ventricle (LV or 4V), 2) that each drug's potency was similar for both LV and 4V injections, 3) that neither LV or 4V injection of these drugs evoked feeding in DSAP-lesioned rats, and 4) that only 5TG, which blocks glycolysis, stimulated a blood glucose response. The antagonist of the MEK/ERK signaling cascade, U0126, attenuated GcA-induced feeding, but not Phl- or 5TG-induced feeding. Thus GcA, Phl, and 5TG, although differing in mechanism and possibly activating different neural populations, stimulate feeding in a catecholamine-dependent manner. Although results do not exclude the possibility that catecholamine neurons possess glucose-sensing mechanisms responsive to all of these agents, currently available evidence favors the possibility that the feeding effects result from convergent neural circuits in which catecholamine neurons are a required component. PMID:24381177

Global concentration additivity and prediction of mixture toxicities, taking nitrobenzene derivatives as an example.

PubMed

Li, Tong; Liu, Shu-Shen; Qu, Rui; Liu, Hai-Ling

2017-10-01

The toxicity of a mixture depends not only on the mixture concentration level but also on the mixture ratio. For a multiple-component mixture (MCM) system with a definite chemical composition, the mixture toxicity can be predicted only if the global concentration additivity (GCA) is validated. The so-called GCA means that the toxicity of any mixture in the MCM system is the concentration additive, regardless of what its mixture ratio and concentration level. However, many mixture toxicity reports have usually employed one mixture ratio (such as the EC 50 ratio), the equivalent effect concentration ratio (EECR) design, to specify several mixtures. EECR mixtures cannot simulate the concentration diversity and mixture ratio diversity of mixtures in the real environment, and it is impossible to validate the GCA. Therefore, in this paper, the uniform design ray (UD-Ray) was used to select nine mixture ratios (rays) in the mixture system of five nitrobenzene derivatives (NBDs). The representative UD-Ray mixtures can effectively and rationally describe the diversity in the NBD mixture system. The toxicities of the mixtures to Vibrio qinghaiensis sp.-Q67 were determined by the microplate toxicity analysis (MTA). For each UD-Ray mixture, the concentration addition (CA) model was used to validate whether the mixture toxicity is additive. All of the UD-Ray mixtures of five NBDs are global concentration additive. Afterwards, the CA is employed to predict the toxicities of the external mixtures from three EECR mixture rays with the NOEC, EC 30 , and EC 70 ratios. The predictive toxicities are in good agreement with the experimental toxicities, which testifies to the predictability of the mixture toxicity of the NBDs. Copyright © 2017. Published by Elsevier Inc.

Love Canal monitoring program. Volume 1. Final report

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

Not Available

This report summarizes the prime contractor activities during the monitoring phase of the Love Canal project. Since GCA Corporation was only responsible for data collection, no analytical results appear in this report. The program involved a multifaceted sampling and analytical effort designed to detect and quantify a variety of trace metals, volatile organics, pesticides and other compounds in soil, sediment, air, biota, and water samples. The principal purpose of these activities was to provide data with which EPA could assess the extent of environmental contamination in the Love Canal Area. Since the area declared as a National Emergency was extendedmore » from those homes directly surrounding the Love Canal dumpsite to a more general area on May 21, 1980, it had been determined that the overall exposure of residents must be established as quickly as possible. The program, therefore, was on an extremely tight schedule with field sampling activities to be completed by October 31, 1980. GCA organized its efforts into seven technical elements, each of which is discussed.« less

The upper mantle beneath the Cascade Range: A comparison with the Gulf of California

NASA Technical Reports Server (NTRS)

Walck, M. C.

1984-01-01

Seismograms from 22 earthquakes along the northeast Pacific rim recorded in southern California form the data set for investigation of the upper mantle beneath the Cascade Range-Juan de Fuca region, a transitional area encompassing both very young ocean floor and a continental margin. These data consist of 853 seismograms (6 deg delta 42 deg) which produce 1068 travel times and 40 ray parameter estimates. These data are compared directly to another large suite of records representative of structure beneath the Gulf of California, an active spreading center. The spreading center model, GCA, was used as a starting point in WKBJ synthetic seismogram modeling and perturb GCA until the northeast Pacific data are matched. Application of wave field continuation to these two groups of data provides checks on model's consistency with the data as well as an estimate of the resolvability of differences between the two areas. Differences between the models derived from these two data sets are interpretable in terms of lateral structural variation beneath the two regimes.

Cellular resolution functional imaging in behaving rats using voluntary head restraint

PubMed Central

Scott, Benjamin B.; Brody, Carlos D.; Tank, David W.

2013-01-01

SUMMARY High-throughput operant conditioning systems for rodents provide efficient training on sophisticated behavioral tasks. Combining these systems with technologies for cellular resolution functional imaging would provide a powerful approach to study neural dynamics during behavior. Here we describe an integrated two-photon microscope and behavioral apparatus that allows cellular resolution functional imaging of cortical regions during epochs of voluntary head restraint. Rats were trained to initiate periods of restraint up to 8 seconds in duration, which provided the mechanical stability necessary for in vivo imaging while allowing free movement between behavioral trials. A mechanical registration system repositioned the head to within a few microns, allowing the same neuronal populations to be imaged on each trial. In proof-of-principle experiments, calcium dependent fluorescence transients were recorded from GCaMP-labeled cortical neurons. In contrast to previous methods for head restraint, this system can also be incorporated into high-throughput operant conditioning systems. PMID:24055015

Motivational Climate in Games Concept Lessons

ERIC Educational Resources Information Center

McNeill, Michael Charles; Fry, Joan Marian; Md. Hairil, Johari

2011-01-01

This is an investigation of the motivational climate generated in games lessons taught by three experienced, specialist physical education (PE) teachers using a tactical games approach (Games Concept Approach, GCA). The pupils' personal motives for participation in the units were also explored. Three PE specialists were purposefully selected to…

CAPILLARY GAS CHROMATOGRAPHY-ATOMIC EMISSION DETECTION METHOD FOR THE DETERMINATION OF PENTYLATED ORGANOTIN COMPOUNDS: INTERLABORATORY STUDY

EPA Science Inventory

A capillary gas chromatography-atomic emission detection (GC-AED) method was developed for the U. S. Environmental Protection Agency's Environmental Monitoring Systems Laboratory in Las Vegas, NV, for determination of selected organotin compounds. Here we report on an interlabora...

Hot N Sour Mantle Soup on Indian Plate During Cretaceous- Evidence from Clumped Isotope and Geochemical Studies of Sung Valley Carbonatite, India

NASA Astrophysics Data System (ADS)

Ghosh, P.; Banerjee, Y.; Tiwari, A.; Srivastava, R. K.

2015-12-01

Geological processes involved in the formation of Carbonatite rocks are complex and so is the understanding about its formational temperature. Fluid inclusion studies (1) on Carbonatite and their associated Ijolites showed a homogenization temperature of 1000-1100°C for Ijoltes and a temperature (T) range of 200-600°C was assigned to the carbonatite melts. Liquid immiscibility process is held responsible for the origin of parental carbonated (ijolititic/ nephelinitic) magma. The homogenization T signifies about a time interval during which there must be a considerable amount of T dropdown soon after the formation of Ijolite and subsequent crystallization of the residual carbonatite magma. However the lack of information about the T of the primary carbonated melt remains as an important area of petrological research. Experimental studies suggest a T range of 950-1400°C for the primary carbonate melt (2). Advent of Clumped isotope thermometry (3) allowed independent method for estimation of the formational T and provide avenues to derive composition of CO2 in equilibrium with carbonate melt. Earlier attempt involving carbonatites from several locations (4) captured range of T between 83°-416°C . Here we present our observation on calcite growth T in the carbonatites from the Cretaceous Sung valley ultramafic-alkaline-carbonatite complex. Based on stable C,O isotope study and Sr, Nd isotopic composition a mantle origin- genetically linked with the Kerguelen plume was proposed (5). Clumped isotope study on the same samples revealed consistent C and O isotope compositions, providing Δ47 values ranging from 0.32 to 0.48. δ13C and δ18O (in VPDB) values of the present study falls within the "Primary Igneous Carbonatite Field" (6). Using high T thermometry equation (7) we obtained a T range of 137-474 °C for the calcite present in the samples. The T recorded in our study is lower than that deduced experimental values of 960-625°C at 0.1 GPa (8) and fluid inclusion based data (1), suggesting involvement of water during calcite crystallization. Ref: 1.Romanchev 1972, Geochem Intern; 2.Gaillard et al., 2008, Science; 3. Ghosh et al.,2006, GCA ; 4. Dennis and Schrag, 2010, GCA; 5. Srivastava et al., 2005. Lithos ; 6.Taylor et al.,1967, GCA; 7. Kluge et al.,2015, GCA, 8. Watkinson and Willey, 1971, Jour. Of Petrology

Solubility of Aragonite in Subduction Water-Rich Fluids

NASA Astrophysics Data System (ADS)

Daniel, I.; Facq, S.; Petitgirard, S.; Cardon, H.; Sverjensky, D. A.

2017-12-01

Carbonate dissolution in subduction zone fluids is critical to the carbon budget in subduction zones. Depending on the solubility of carbonate minerals in aqueous fluids, the subducting lithosphere may be either strongly depleted and the mantle metasomatized if the solubility is high, as recently suggested by natural samples or transport carbon deeper into the Earth's mantle if the solubility is low enough [1, 2]. Dissolution of carbonate minerals strongly depends on pressure and temperature as well as on the chemistry of the fluid, leading to a highly variable speciation of aqueous carbon. Thanks to recent advances in theoretical aqueous geochemistry [3, 4], combined experimental and theoretical efforts now allow the investigation of speciation and solubility of carbonate minerals in aqueous fluids at PT conditions higher than previously feasible [4, 5]. In this study, we present new in situ X-ray fluorescence measurements of aragonite dissolution up to 5 GPa and 500°C and the subsequent thermodynamic model of aragonite solubility in aqueous fluids thanks to the Deep Earth Water model. The amount of dissolved aragonite in the fluid was calculated from challenging and unprecedented measurements of the Ca fluorescence K-lines at low-energy. Experiments were performed at the ESRF, beamline ID27 using a dedicated design of an externally-heated diamond anvil cell and an incident high-flux and highly focused monochromatic X-Ray beam at 20 keV. The results show a spectacularly high solubility of aragonite at HP-HT in water, further enhanced in presence of NaCl and silica in the solution. [1] Frezzotti, M. L. et al. (2011) doi:10.1038/ngeo1246. [2] Ague, J. J. and Nicolescu, S. (2014) doi:10.1038/ngeo2143. [3] Pan, D. et al. (2013) doi: 10.1073/pnas.1221581110. [4] Sverjensky, D. A et al. (2014) doi: 10.1016/j.gca.2013.12.019. [5] Facq, S. et al. (2014) doi: 10.1016/j.gca.2014.01.030.

SIMULTANEOUS DETERMINATION OF ORGANOTIN, ORGANOLEAD, AND ORGANOMERCURY COMPOUNDS IN ENVIRONMENTAL SAMPLES USING CAPILLARY GAS CHROMATOGRAPHY WITH ATOMIC EMISSION DETECTION

EPA Science Inventory

As part of a continuing evaluation of new analytical and sample preparation techniques conducted by the US Environmental Protection Agency (EPA), the use of capillary gas chromatography with atomic emission detection (GC-AED) for the simultaneous determination of organotin, organ...

Parental GCA testing: how many crosses per parent?

Treesearch

G.R. Johnson

1998-01-01

The impact of increasing the number of crosses per parent (k) on the efficiency of roguing seed orchards (backwards selection, i.e., reselection of parents) was examined by using Monte Carlo simulation. Efficiencies were examined in light of advanced-generation Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) tree improvement programs where...

78 FR 52982 - Regal Beloit Corporation; Springfield, Missouri Division Including On-site Leased Workers From...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-27

... these workers were sufficiently under the control of the subject firm to be considered leased workers...; Springfield, Missouri Division Including On-site Leased Workers From Penmac Personnel Services and GCA Services Group Springfield, Missouri; Amended Certification Regarding Eligibility to Apply for Worker...

LOVE CANAL MONITORING PROGRAM. GCA QA/QC (QUALITY ASSURANCE/QUALITY CONTROL) SUMMARY REPORT

EPA Science Inventory

One of the most important responsibilities of the Love Canal prime contractor was the institution and maintenance of a quality assurance program. An important objective of the quality assurance program was to alert the subcontractors to the importance of high quality work on thei...

COMPARISON OF GC-FPD AND GC/AED FOR DETERMINATION OF ORGANOPHOSPHATE PESTICIDES IN COMPOSITE DIET SAMPLES

EPA Science Inventory

In order to assess an individual's total exposure to contaminants in the environment, it is essential that the contribution of dietary exposure be quantified. As a result, USEPA's National Exposure Research Laboratory has initiated a program to develop methods to measure chemical...

Solar Noble Gases in Polymict Ureilites and an Update on Ureilite Noble Gas Data

NASA Astrophysics Data System (ADS)

Ott, U.; Lohr, H. P.; Begemann, F.

1993-07-01

Ureilites are one of the least understood classes of meteorites; they show signs of being processed, but also appear to be primitive, with abundant carbon and trapped noble gases [1-6]. We have now begun to analyze a number of recently recovered specimens: one from the Saharan desert (Acfer 277) amd five from the Antarctic (LEW 85328, LEW 85440, EET 87720, FRO 90036, and FRO 90054). Analyses of Acfer 277, LEW 85328, and EET 87720 are complete (Table 1). Solar noble gases are present in polymict EET 87720, as shown by the three- isotope plot of Fig. 1. There, in contrast to the bulk data point for Acfer 277, data points for EET 87720 deviate from a mixing line between "typical" spallation Ne (as approximated here by the spallation-dominated 1800 degrees C step for EET 87720) and Ne-U [7] toward higher ^20Ne/^22Ne. A line fitted to the EET 87720 data points passes slightly below Ne-B [8]. The situation is similar for sample F1 from polymict EET 83309 [9], which is shown for comparison. Additional support for the presence of solar gases arises from the abundance of ^4He (~9 x 10^-5 cm^3 STP/g in EET 87720-F1, corrected for spallogenic contributions), which in both cases is far higher than in other ureilite bulk samples [6,10]. Also, in the ratio of spallation-corrected ^4He to trapped ^36Ar, these two polymict ureilites clearly stand out. Helium-4/argon-36 ratios in EET 87720-F1 and EET 83309-F1 are ~20 and ~28 respectively, at least 1 order of magnitude higher than in bulk monomict ureilites and 2 orders of magnitude higher than what appears typical of ureilite diamonds [6]. Nilpena, another polymict ureilite [11], also has a ^4He/^36Ar ratio (2.1 in Nilpena II-1 [7]) higher than all monomict ureilites but one (Dingo Pup Donga), indicating the presence of solar noble gases (in variable contents) as a possible general feature of polymict ureilites, similar to the presence in them of nitrogen with high delta(^15N/^14N) [12]. Monomict LEW 85328 has a very high (^22Ne/^21Ne)(sub)c ratio of the cosmogenic component, indicative of irradiation under very low shielding conditions, but otherwise abundances and abundance ratios for the momomict ureilites LEW 85328 and Acfer 277 appear quite "ordinary" when compared to other monomict ureilites [6,10]. References: [1] Wasson J. T. et al. (1976) GCA, 40, 1449-1458. [2] Berkley J. L. et al. (1980) GCA, 44, 1579-1597. [3] Takeda H. (1989) EPSL, 93, 181- 194. [4] Warren P. H. and Kallemeyn G. W. (1989) Meteoritics, 24, 233-246. [5] Clayton R. N. and Mayeda T. K. (1988) GCA, 52, 1313-1318. [6] Gobel R. et al. (1978) JGR, 83, 855-867. [7] Ott U. et al. (1984) Meteoritics, 19, 287-288. [8] Black D. C. (1972) GCA, 36, 347-375. [9] Ott U. et al. (1990) Meteoritics, 25, 396. [10] Schultz L. and Kruse H. (1989) Meteoritics, 24, 155-172. [11] Jaques A. L. and Fitzgerald M. J. (1982) GCA, 46, 893-900. [12] Grady M. M. and Pillinger C. T. (1988) Nature, 331, 321-323. Table 1, which appears here in the hard copy, shows noble gases in monomict ureilites Acfer 277 and LEW 85328 and polymict ureilite EET 87720. Fig. 1 appears here in the hard copy.

Minimally invasive multimode optical fiber microendoscope for deep brain fluorescence imaging

PubMed Central

Ohayon, Shay; Caravaca-Aguirre, Antonio; Piestun, Rafael; DiCarlo, James J.

2018-01-01

A major open challenge in neuroscience is the ability to measure and perturb neural activity in vivo from well defined neural sub-populations at cellular resolution anywhere in the brain. However, limitations posed by scattering and absorption prohibit non-invasive multi-photon approaches for deep (>2mm) structures, while gradient refractive index (GRIN) endoscopes are relatively thick and can cause significant damage upon insertion. Here, we present a novel micro-endoscope design to image neural activity at arbitrary depths via an ultra-thin multi-mode optical fiber (MMF) probe that has 5–10X thinner diameter than commercially available micro-endoscopes. We demonstrate micron-scale resolution, multi-spectral and volumetric imaging. In contrast to previous approaches, we show that this method has an improved acquisition speed that is sufficient to capture rapid neuronal dynamics in-vivo in rodents expressing a genetically encoded calcium indicator (GCaMP). Our results emphasize the potential of this technology in neuroscience applications and open up possibilities for cellular resolution imaging in previously unreachable brain regions. PMID:29675297

Gold nanoparticle-assisted all optical localized stimulation and monitoring of Ca2+ signaling in neurons

PubMed Central

Lavoie-Cardinal, Flavie; Salesse, Charleen; Bergeron, Éric; Meunier, Michel; De Koninck, Paul

2016-01-01

Light-assisted manipulation of cells to control membrane activity or intracellular signaling has become a major avenue in life sciences. However, the ability to perform subcellular light stimulation to investigate localized signaling has been limited. Here, we introduce an all optical method for the stimulation and the monitoring of localized Ca2+ signaling in neurons that takes advantage of plasmonic excitation of gold nanoparticles (AuNPs). We show with confocal microscopy that 800 nm laser pulse application onto a neuron decorated with a few AuNPs triggers a transient increase in free Ca2+, measured optically with GCaMP6s. We show that action potentials, measured electrophysiologically, can be induced with this approach. We demonstrate activation of local Ca2+ transients and Ca2+ signaling via CaMKII in dendritic domains, by illuminating a single or few functionalized AuNPs specifically targeting genetically-modified neurons. This NP-Assisted Localized Optical Stimulation (NALOS) provides a new complement to light-dependent methods for controlling neuronal activity and cell signaling. PMID:26857748

Structuring Time and Questioning to Achieve Tactical Awareness in Games Lessons

ERIC Educational Resources Information Center

McNeill, Michael C.; Fry, Joan M.; Wright, Steven C.; Tan, Clara W. K.; Rossi, Tony

2008-01-01

Background: A paradigm shift in educational policy to create problem solvers and critical thinkers produced the games concept approach (GCA) in Singapore's Revised Syllabus for Physical Education (1999). A pilot study (2001) conducted on 11 primary school student teachers (STs) using this approach identified time management and questioning as two…

Aberrant Cortical Activity in Multiple GCaMP6-Expressing Transgenic Mouse Lines

PubMed Central

Buetfering, Christina; Groblewski, Peter A.; Manavi, Sahar; Miles, Jesse; White, Casey; Griffin, Fiona; Roll, Kate; Cross, Sissy; Nguyen, Thuyanh V.; Larsen, Rachael; Daigle, Tanya; Thompson, Carol L.; Olsen, Shawn; Hausser, Michael

2017-01-01

Abstract Transgenic mouse lines are invaluable tools for neuroscience but, as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, of either sex, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, although rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study. PMID:28932809

Management of peri-anal giant condyloma acuminatum--a case report and literature review.

PubMed

Safi, Farouk; Bekdache, Omar; Al-Salam, Suhail; Alashari, Mouied; Mazen, Taha; El-Salhat, Haytham

2013-01-01

Giant condyloma acuminatum (GCA), originally described by Buschke and Loewenstein in 1925 as a lesion of the penis, is more rarely seen in the anorectum and is characterized by clinical malignancy in the face of histologic benignity; however, malignant transformation to frankly invasive squamous-cell carcinoma has been described in about one-third of patients. In addition, malignant transformation has been reported in patients with "ordinary" condylomata acuminata. Human papillomavirus, known to cause condylomata acuminata, is also known to induce these tumors and was found in 96% of 63 cases reviewed in the last 10 years. These lesions have a propensity for recurrence and a likelihood of malignant transformation, and lead to significant mortality. Therefore, early and radical R0 excision, along with vigilant follow-up, provides the hope for cure. Conservative and/or multimodal therapy has been reported in a few cases, but its effect is not yet proved. The authors report one case of GCA; in addition, they reviewed the literature over the last 10 years and compared with previous reviews. Copyright © 2012. Published by Elsevier B.V.

Measurement of surface contamination by certain antineoplastic drugs using high-performance liquid chromatography: applications in occupational hygiene investigations in hospital environments.

PubMed

Rubino, F M; Floridia, L; Pietropaolo, A M; Tavazzani, M; Colombi, A

1999-01-01

Within the context of continuing interest in occupational hygiene of hospitals as workplaces, the authors report the results of a preliminary study on surface contamination by certain antineoplastic drugs (ANDs), recently performed in eight cancer departments of two large general hospitals in Milan, Italy. Since reliable quantitative information on the exposure levels to individual drugs is mandatory to establish a strong interpretative framework for correctly assessing the health risks associated with manipulation of ANDs and rationally advise intervention priorities for exposure abatement, two automated analytical methods were set up using reverse-phase high-performance liquid chromatography for the measurement of contamination by 1) methotrexate (MTX) and 2) the three most important nucleoside analogue antineoplastic drugs (5-fluorouracil 5FU, Cytarabin CYA, Gemcytabin GCA) on surfaces such as those of preparation hoods and work-benches in the pharmacies of cancer wards. The methods are characterized by short analysis time (7 min) under isocratic conditions, by the use of a mobile phase with a minimal content of organic solvent and by high sensitivity, adequate to detect surface contamination in the 5-10 micrograms/m2 range. To exemplify the performance of the analytical methods in the assessment of contamination levels from the target analyte ANDs, data are reported on the contamination levels measured on various surfaces (such as on handles, floor surfaces and window panes, even far from the preparation hood). Analyte concentrations corresponding to 0.8-1.5 micrograms of 5FU were measured on telephones, 0.85-28 micrograms/m2 of CYA were measured on tables, 1.2-1150 micrograms/m2 of GCA on furniture and floors. Spillage fractions between 1-5% of the used ANDs (daily use 5FU 7-13 g; CYA 0.1-7.1 g; GCA 0.2-5 g) were measured on the disposable polythene-backed paper cover sheet of the preparation hood.

Position-specific isotope analysis by on-line pyrolysis coupled to IRMS

NASA Astrophysics Data System (ADS)

Gilbert, A.; Suda, K.; Yamada, K.; Ueno, Y.; Yoshida, N.

2016-12-01

Position-specific isotopic analyses (PSIA) provide unique information regarding the sources, sinks and processes related to natural molecules. For instance, PSIA of short-chain hydrocarbons could lead to temperature of formation and maturity of natural gas reservoirs [1][2]. In the last decade, quantitative Nuclear Magnetic Resonance (NMR) specrometry has been used for PSIA of organic molecules such as glucose or n-alkanes [3][4]. However, due to its low sensitivity, application to low amount geochemical samples remains challenging. In 1997, Corso & Brenna proposed to adapt a pyrolysis furnace to an isotope ratio mass spectrometer, making it possible the thermal degradation of the target molecule and the subsequent analysis of the d13C values of the fragments formed [5]. Starting from fatty acid methyl esters they demonstrated the absence of rearrangement during pyrolytic degradation and could determine the d13C value of carboxyl C-atom position. We adapted the system for the full characterization of position-specific isotope composition of small molecules (ethanol, acetic acid, alanine, propane). Nanomole amount of sample can be analyzed with a precision on intramolecular d13C values of 1‰ or lower [2]. We recently analyzed abiotic and thermogenic propane samples both from the field and from lab simulations. PSIA of propane shows systematic differences of position-specific isotope composition between thermogenic and abiotic samples. While the former show 13C-depletion on the terminal C-atom position - consistent with thermal cracking kinetic models [6] - abiotic samples show little or no preference for terminal or central 13C-isotopomer. These results emphasize the potential of PSIA to trace the the processes associated with organic molecules production. [1] Piasecki et al. 2016 GCA 188, 58 [2] Gilbert et al. 2016 GCA 177, 205 [3] Gilbert et al. 2012 PNAS, 109, 18204 [4] Gilbert et al. 2013 Org. Geochem, 62, 56 [5] Corso & Brenna 1997 PNAS, 94, 1049 [6] Tang et al., 2000 GCA 64, 2673

Endothelial actions of atrial and B-type natriuretic peptides.

PubMed

Kuhn, Michaela

2012-05-01

The cardiac hormone atrial natriuretic peptide (ANP) is critically involved in the maintenance of arterial blood pressure and intravascular volume homeostasis. Its cGMP-producing GC-A receptor is densely expressed in the microvascular endothelium of the lung and systemic circulation, but the functional relevance is controversial. Some studies reported that ANP stimulates endothelial cell permeability, whereas others described that the peptide attenuates endothelial barrier dysfunction provoked by inflammatory agents such as thrombin or histamine. Many studies in vitro addressed the effects of ANP on endothelial proliferation and migration. Again, both pro- and anti-angiogenic properties were described. To unravel the role of the endothelial actions of ANP in vivo, we inactivated the murine GC-A gene selectively in endothelial cells by homologous loxP/Cre-mediated recombination. Our studies in these mice indicate that ANP, via endothelial GC-A, increases endothelial albumin permeability in the microcirculation of the skin and skeletal muscle. This effect is critically involved in the endocrine hypovolaemic, hypotensive actions of the cardiac hormone. On the other hand the homologous GC-A-activating B-type NP (BNP), which is produced by cardiac myocytes and many other cell types in response to stressors such as hypoxia, possibly exerts more paracrine than endocrine actions. For instance, within the ischaemic skeletal muscle BNP released from activated satellite cells can improve the regeneration of neighbouring endothelia. This review will focus on recent advancements in our understanding of endothelial NP/GC-A signalling in the pulmonary versus systemic circulation. It will discuss possible mechanisms accounting for the discrepant observations made for the endothelial actions of this hormone-receptor system and distinguish between (patho)physiological and pharmacological actions. Lastly it will emphasize the potential therapeutical implications derived from the actions of NPs on endothelial permeability and regeneration. © 2012 The Author. British Journal of Pharmacology © 2012 The British Pharmacological Society.

PM2.5 forecasting using SVR with PSOGSA algorithm based on CEEMD, GRNN and GCA considering meteorological factors

NASA Astrophysics Data System (ADS)

Zhu, Suling; Lian, Xiuyuan; Wei, Lin; Che, Jinxing; Shen, Xiping; Yang, Ling; Qiu, Xuanlin; Liu, Xiaoning; Gao, Wenlong; Ren, Xiaowei; Li, Juansheng

2018-06-01

The PM2.5 is the culprit of air pollution, and it leads to respiratory system disease when the fine particles are inhaled. Therefore, it is increasingly significant to develop an effective model for PM2.5 forecasting and warnings that informs people to foresee the air quality. People can reduce outdoor activities and take preventive measures if they know the air quality is bad ahead of time. In addition, reliable forecasting results can remind the relevant departments to control and reduce pollutants discharge. According to our knowledge, the current hybrid forecasting techniques of PM2.5 do not take the meteorological factors into consideration. Actually, meteorological factors affect the concentrations of air pollution, but it is unclear whether meteorological factors are helpful for improving the PM2.5 forecasting results or not. This paper proposes a hybrid model called CEEMD-PSOGSA-SVR-GRNN, based on complementary ensemble empirical mode decomposition (CEEMD), particle swarm optimization and gravitational search algorithm (PSOGSA), support vector regression (SVR), generalized regression neural network (GRNN) and grey correlation analysis (GCA), for the daily PM2.5 concentrations forecasting. The main steps of proposed model are described as follows: the original PM2.5 data decomposition with CEEMD, optimal SVR selection with PSOGCA, meteorological factors selection with GCA, residual revision by GRNN and forecasting results analysis. Three cities (Chongqing, Harbin and Jinan) in China with different characteristics of climate, terrain and pollution sources are selected to verify the effectiveness of proposed model, and CEEMD-PSOGSA-SVR*, EEMD-PSOGSA-SVR, PSOGSA-SVR, CEEMD-PSO-SVR, CEEMD-GSA-SVR, CEEMD-GWO-SVR are considered to be compared models. The experimental results show that the hybrid CEEMD-PSOGSA-SVR-GRNN model outperforms other six compared models. Therefore, the proposed CEEMD-PSOGSA-SVR-GRNN model can be used to develop air quality forecasting and warnings.

Expression of membrane-bound and cytosolic guanylyl cyclases in the rat inner ear.

PubMed

Seebacher, T; Beitz, E; Kumagami, H; Wild, K; Ruppersberg, J P; Schultz, J E

1999-01-01

Membrane-bound guanylyl cyclases (GCs) are peptide hormone receptors whereas the cytosolic isoforms are receptors for nitric oxide. In the inner ear, the membrane-bound GCs may be involved in the regulation of fluid homeostasis and the cytosolic forms possibly play a role in signal processing and regulation of local blood flow. In this comprehensive study, we examined, qualitatively and quantitatively, the transcription pattern of all known GC isoforms in the inner ear from rat by RT-PCR. The tissues used were endolymphatic sac, stria vascularis, organ of Corti, organ of Corti outer hair cells, cochlear nerve, Reissner's membrane, vestibular dark cells, and vestibular sensory cells. We show that multiple particulate (GC-A, GC-B, GC-D, GC-E, GC-F and GC-G) and several subunits of the heterodimeric cytosolic GCs (alpha1, alpha2, beta1 and beta2) are expressed, albeit at highly different levels. GC-C was not found. GC-A and the soluble subunits alpha1 and beta1 were transcribed ubiquitously. GC-B was present in all tissues except stria vascularis, which contained GC-A and traces of GC-E and GC-G. GC-B was by far the predominant membrane-bound isoform in the organ of Corti (86%), Reissner's membrane (75%) and the vestibulum (80%). Surprisingly, GC-E, a retinal isoform, was detected in significant amounts in the cochlear nerve (8%) and in the organ of Corti (4%). Although the cytosolic GC is a heterodimer composed of an alpha and a beta subunit, the mRNA transcription of these subunits was not stoichiometric. Particularly in the vestibulum, the transcription of the beta1 subunits was at least four-fold higher than of the alpha1 subunit. The data are compatible with earlier suggestions that membrane receptor GCs may be involved in the control of inner ear electrolyte and fluid composition whereas NO-stimulated GC isoforms mainly participate in the regulation of blood flow and supporting cell physiology.

Cholesterol import and steroidogenesis are biosignatures for gastric cancer patient survival

PubMed Central

Chang, Wei-Chun; Huang, Shang-Fen; Lee, Yang-Ming; Lai, Hsueh-Chou; Cheng, Bi-Hua; Cheng, Wei-Chung; Ho, Jason Yen-Ping; Jeng, Long-Bin; Ma, Wen-Lung

2017-01-01

Androgens, estrogens, progesterone and related signals are reported to be involved in the pathology of gastric cancer. However, varied conclusions exist based on serum hormone levels, receptor expressions, and in vitro or in vivo studies. This report used a web-based gene survival analyzer to evaluate biochemical processes, including cholesterol importing via lipoprotein/receptors (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer patients prognosis. The sex hormone receptors (androgen receptor, progesterone receptor, and estrogen receptor ESR1 or ESR2), L/R route (low/high-density lipoprotein receptors, LDLR/LRP6/SR-B1 and lipoprotein lipase, LPL) and steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and SRD5A1) were associated with 5-year survival of gastric cancer patients. The AR, PR, ESR1 and ESR2 are progression promoters, as are the L/R route LDLR, LRP6, SR-B1 and LPL. It was found that CYP11A1, HSD3B1, CYP17, HSD17B1 and CYP19A1 promote progression, but dihydrotestosterone (DHT) converting enzyme SRD5A1 suppresses progression. Analyzing steroidogenic lipidome with a hazard ratio score algorithm found that CYP19A1 is the progression confounder in surgery, HER2 positive or negative patients. Finally, in the other patient cohort from TCGA, CYP19A1 was expressed higher in the tumor compared to that in normal counterparts, and also promoted progression. Lastly, exemestrane (type II aromatase inhibitor) dramatically suppress GCa cell growth in pharmacological tolerable doses in vitro. This work depicts a route-specific outside-in delivery of cholesterol to promote disease progression, implicating a host-to-tumor macroenvironmental regulation. The result indicating lipoprotein-mediated cholesterol entry and steroidogenesis are GCa progression biosignatures. And the exemestrane clinical trial in GCa patients of unmet medical needs is suggested. PMID:27893427

Cholesterol import and steroidogenesis are biosignatures for gastric cancer patient survival.

PubMed

Chang, Wei-Chun; Huang, Shang-Fen; Lee, Yang-Ming; Lai, Hsueh-Chou; Cheng, Bi-Hua; Cheng, Wei-Chung; Ho, Jason Yen-Ping; Jeng, Long-Bin; Ma, Wen-Lung

2017-01-03

Androgens, estrogens, progesterone and related signals are reported to be involved in the pathology of gastric cancer. However, varied conclusions exist based on serum hormone levels, receptor expressions, and in vitro or in vivo studies. This report used a web-based gene survival analyzer to evaluate biochemical processes, including cholesterol importing via lipoprotein/receptors (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer patients prognosis. The sex hormone receptors (androgen receptor, progesterone receptor, and estrogen receptor ESR1 or ESR2), L/R route (low/high-density lipoprotein receptors, LDLR/LRP6/SR-B1 and lipoprotein lipase, LPL) and steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and SRD5A1) were associated with 5-year survival of gastric cancer patients. The AR, PR, ESR1 and ESR2 are progression promoters, as are the L/R route LDLR, LRP6, SR-B1 and LPL. It was found that CYP11A1, HSD3B1, CYP17, HSD17B1 and CYP19A1 promote progression, but dihydrotestosterone (DHT) converting enzyme SRD5A1 suppresses progression. Analyzing steroidogenic lipidome with a hazard ratio score algorithm found that CYP19A1 is the progression confounder in surgery, HER2 positive or negative patients. Finally, in the other patient cohort from TCGA, CYP19A1 was expressed higher in the tumor compared to that in normal counterparts, and also promoted progression. Lastly, exemestrane (type II aromatase inhibitor) dramatically suppress GCa cell growth in pharmacological tolerable doses in vitro. This work depicts a route-specific outside-in delivery of cholesterol to promote disease progression, implicating a host-to-tumor macroenvironmental regulation. The result indicating lipoprotein-mediated cholesterol entry and steroidogenesis are GCa progression biosignatures. And the exemestrane clinical trial in GCa patients of unmet medical needs is suggested.

Modeling the Economic Impacts of Large Deployments on Local Communities

DTIC Science & Technology

2008-12-01

MODELING THE ECONOMIC IMPACTS OF LARGE DEPLOYMENTS ON LOCAL COMMUNITIES THESIS Aaron L... MODELING THE ECONOMIC IMPACTS OF LARGE DEPLOYMENTS ON LOCAL COMMUNITIES THESIS Presented to the Faculty Department of Systems Engineering and...APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED AFIT/GCA/ENV/08-D01 MODELING THE ECONOMIC IMPACTS OF LARGE DEPLOYMENTS ON LOCAL

International Student Experience: What It Is, What It Means and Why It Matters

ERIC Educational Resources Information Center

Thakur, Marian; Hourigan, Clare

2007-01-01

The Course Experience Questionnaire (CEQ) was administered to recent university graduates by Graduate Careers Australia (GCA) in order to obtain feedback about their perceptions of their course. Students were asked to rate the extent to which they agree with a series of 49 statements covering issues surrounding the education and support services…

Automated Video-Based Analysis of Contractility and Calcium Flux in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Cultured over Different Spatial Scales.

PubMed

Huebsch, Nathaniel; Loskill, Peter; Mandegar, Mohammad A; Marks, Natalie C; Sheehan, Alice S; Ma, Zhen; Mathur, Anurag; Nguyen, Trieu N; Yoo, Jennie C; Judge, Luke M; Spencer, C Ian; Chukka, Anand C; Russell, Caitlin R; So, Po-Lin; Conklin, Bruce R; Healy, Kevin E

2015-05-01

Contractile motion is the simplest metric of cardiomyocyte health in vitro, but unbiased quantification is challenging. We describe a rapid automated method, requiring only standard video microscopy, to analyze the contractility of human-induced pluripotent stem cell-derived cardiomyocytes (iPS-CM). New algorithms for generating and filtering motion vectors combined with a newly developed isogenic iPSC line harboring genetically encoded calcium indicator, GCaMP6f, allow simultaneous user-independent measurement and analysis of the coupling between calcium flux and contractility. The relative performance of these algorithms, in terms of improving signal to noise, was tested. Applying these algorithms allowed analysis of contractility in iPS-CM cultured over multiple spatial scales from single cells to three-dimensional constructs. This open source software was validated with analysis of isoproterenol response in these cells, and can be applied in future studies comparing the drug responsiveness of iPS-CM cultured in different microenvironments in the context of tissue engineering.

Linking Neurons to Network Function and Behavior by Two-Photon Holographic Optogenetics and Volumetric Imaging.

PubMed

Dal Maschio, Marco; Donovan, Joseph C; Helmbrecht, Thomas O; Baier, Herwig

2017-05-17

We introduce a flexible method for high-resolution interrogation of circuit function, which combines simultaneous 3D two-photon stimulation of multiple targeted neurons, volumetric functional imaging, and quantitative behavioral tracking. This integrated approach was applied to dissect how an ensemble of premotor neurons in the larval zebrafish brain drives a basic motor program, the bending of the tail. We developed an iterative photostimulation strategy to identify minimal subsets of channelrhodopsin (ChR2)-expressing neurons that are sufficient to initiate tail movements. At the same time, the induced network activity was recorded by multiplane GCaMP6 imaging across the brain. From this dataset, we computationally identified activity patterns associated with distinct components of the elicited behavior and characterized the contributions of individual neurons. Using photoactivatable GFP (paGFP), we extended our protocol to visualize single functionally identified neurons and reconstruct their morphologies. Together, this toolkit enables linking behavior to circuit activity with unprecedented resolution. Copyright © 2017 Elsevier Inc. All rights reserved.

All-optical recording and stimulation of retinal neurons in vivo in retinal degeneration mice

PubMed Central

Strazzeri, Jennifer M.; Williams, David R.; Merigan, William H.

2018-01-01

Here we demonstrate the application of a method that could accelerate the development of novel therapies by allowing direct and repeatable visualization of cellular function in the living eye, to study loss of vision in animal models of retinal disease, as well as evaluate the time course of retinal function following therapeutic intervention. We use high-resolution adaptive optics scanning light ophthalmoscopy to image fluorescence from the calcium sensor GCaMP6s. In mice with photoreceptor degeneration (rd10), we measured restored visual responses in ganglion cell layer neurons expressing the red-shifted channelrhodopsin ChrimsonR over a six-week period following significant loss of visual responses. Combining a fluorescent calcium sensor, a channelrhodopsin, and adaptive optics enables all-optical stimulation and recording of retinal neurons in the living eye. Because the retina is an accessible portal to the central nervous system, our method also provides a novel non-invasive method of dissecting neuronal processing in the brain. PMID:29596518

Mating design considerations—How many crosses do we really need to test?

Treesearch

R. Johnson

2000-01-01

The impact of increasing the number of crosses per parent on the efficiency of backwards selection was examined using Monte Carlo simulation. Both the efficiency of reselection and its associated variance leveled off after two to three crosses per parent.Because so few crosses appear to be needed to estimate parental GCA values, a quasi-complementary mating...

77 FR 33630 - Residency Requirements for Aliens Acquiring Firearms (2011R-23P)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-07

... acquire a firearm. The Department has determined that the Gun Control Act does not permit ATF to impose a... the Gun Control Act of 1968 (GCA), 18 U.S.C. 922(b)(3), makes it unlawful for a Federal firearms... the Gun Control Act cannot have two different constructions, one that applies to U.S. citizens and...

Alternative Active Duty Military Retirement Plan

DTIC Science & Technology

2011-03-24

savings. v AFIT/GCA/ENS/11-02 This work is dedicated to all the hardworking men and women in...discovering innovative ways to save money without decreasing the quality of life for their customers. The federal government is no different, and is...living adjustment, and life expectancy. The results could be distorted in the wake of a significant economic event. Sensitivity analysis was

Formative Research and Teen SMART: Try, Try Again. Reports and Papers in Progress. Report No. 90-3.

ERIC Educational Resources Information Center

Ellis, Jan

"Teen SMART" is the working title of the high school age component of Operation SMART, a larger curriculum development project initiated by Girls Clubs of America, Inc. (GCA) to promote the participation of girls and young women in science, mathematics, and technology. Operation SMART seeks not only to attract and involve those girls who…

Molecular Genetic Studies of Bone Mechanical Strain and of Pedigrees with Very High Bone Density

DTIC Science & Technology

2009-11-01

mice. We used Cre-recombinase primer (F- TTA GCA CCA CGG CAG CAG GAG GTT and R-CAG GCC AGA TCT CCT GTG CAG CAT) and loxp primer (Primer 1, AGT GAT...Leprdb heterozygotes during breeding. Three types of littermates are produced from breeding these heterozygotes: the misty gray homozygote (m +/m +), the

Correlation of MRI Visual Scales with Neuropsychological Profile in Mild Cognitive Impairment of Parkinson's Disease.

PubMed

Vasconcellos, Luiz Felipe; Pereira, João Santos; Adachi, Marcelo; Greca, Denise; Cruz, Manuela; Malak, Ana Lara; Charchat-Fichman, Helenice; Spitz, Mariana

2017-01-01

Few studies have evaluated magnetic resonance imaging (MRI) visual scales in Parkinson's disease-Mild Cognitive Impairment (PD-MCI). We selected 79 PD patients and 92 controls (CO) to perform neurologic and neuropsychological evaluation. Brain MRI was performed to evaluate the following scales: Global Cortical Atrophy (GCA), Fazekas, and medial temporal atrophy (MTA). The analysis revealed that both PD groups (amnestic and nonamnestic) showed worse performance on several tests when compared to CO. Memory, executive function, and attention impairment were more severe in amnestic PD-MCI group. Overall analysis of frequency of MRI visual scales by MCI subtype did not reveal any statistically significant result. Statistically significant inverse correlation was observed between GCA scale and Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), semantic verbal fluency, Stroop test, figure memory test, trail making test (TMT) B, and Rey Auditory Verbal Learning Test (RAVLT). The MTA scale correlated with Stroop test and Fazekas scale with figure memory test, digit span, and Stroop test according to the subgroup evaluated. Visual scales by MRI in MCI should be evaluated by cognitive domain and might be more useful in more severely impaired MCI or dementia patients.

Skeleton-Based Human Action Recognition With Global Context-Aware Attention LSTM Networks

NASA Astrophysics Data System (ADS)

Liu, Jun; Wang, Gang; Duan, Ling-Yu; Abdiyeva, Kamila; Kot, Alex C.

2018-04-01

Human action recognition in 3D skeleton sequences has attracted a lot of research attention. Recently, Long Short-Term Memory (LSTM) networks have shown promising performance in this task due to their strengths in modeling the dependencies and dynamics in sequential data. As not all skeletal joints are informative for action recognition, and the irrelevant joints often bring noise which can degrade the performance, we need to pay more attention to the informative ones. However, the original LSTM network does not have explicit attention ability. In this paper, we propose a new class of LSTM network, Global Context-Aware Attention LSTM (GCA-LSTM), for skeleton based action recognition. This network is capable of selectively focusing on the informative joints in each frame of each skeleton sequence by using a global context memory cell. To further improve the attention capability of our network, we also introduce a recurrent attention mechanism, with which the attention performance of the network can be enhanced progressively. Moreover, we propose a stepwise training scheme in order to train our network effectively. Our approach achieves state-of-the-art performance on five challenging benchmark datasets for skeleton based action recognition.

4-dimensional functional profiling in the convulsant-treated larval zebrafish brain.

PubMed

Winter, Matthew J; Windell, Dylan; Metz, Jeremy; Matthews, Peter; Pinion, Joe; Brown, Jonathan T; Hetheridge, Malcolm J; Ball, Jonathan S; Owen, Stewart F; Redfern, Will S; Moger, Julian; Randall, Andrew D; Tyler, Charles R

2017-07-26

Functional neuroimaging, using genetically-encoded Ca 2+ sensors in larval zebrafish, offers a powerful combination of high spatiotemporal resolution and higher vertebrate relevance for quantitative neuropharmacological profiling. Here we use zebrafish larvae with pan-neuronal expression of GCaMP6s, combined with light sheet microscopy and a novel image processing pipeline, for the 4D profiling of chemoconvulsant action in multiple brain regions. In untreated larvae, regions associated with autonomic functionality, sensory processing and stress-responsiveness, consistently exhibited elevated spontaneous activity. The application of drugs targeting different convulsant mechanisms (4-Aminopyridine, Pentylenetetrazole, Pilocarpine and Strychnine) resulted in distinct spatiotemporal patterns of activity. These activity patterns showed some interesting parallels with what is known of the distribution of their respective molecular targets, but crucially also revealed system-wide neural circuit responses to stimulation or suppression. Drug concentration-response curves of neural activity were identified in a number of anatomically-defined zebrafish brain regions, and in vivo larval electrophysiology, also conducted in 4dpf larvae, provided additional measures of neural activity. Our quantification of network-wide chemoconvulsant drug activity in the whole zebrafish brain illustrates the power of this approach for neuropharmacological profiling in applications ranging from accelerating studies of drug safety and efficacy, to identifying pharmacologically-altered networks in zebrafish models of human neurological disorders.

Evaluating sourcing and fluvial integration of plant wax biomarkers from the Peruvian Andes to Amazonian lowlands

NASA Astrophysics Data System (ADS)

Wu, M. S.; Feakins, S. J.; Ponton, C.; West, A. J.; Galy, V.

2017-12-01

The carbon and hydrogen isotopic compositions (respectively δ13C and δD) of plant wax biomarkers have been widely used to reconstruct past climate and environment. To understand how leaf waxes are sourced within a river catchment, and how their isotopic signature is transferred from source to sink, we study δ13C and δD of C29 n-alkanes and C30 n-alkanoic acids in the Madre de Dios River catchment along the eastern flank of the Peruvian Andes. We sampled soils across a 3.5km elevation transect and find gradients in δ13Cwax (ca. +1.5‰/km) and δDwax (ca. -10 ‰/km) similar to gradients in tree canopy leaves (Feakins et al., 2016 GCA; Wu et al., 2017 GCA). We also collected river suspended sediment samples along the Madre de Dios River and its tributaries, which together drain an area of 75,400 km2 and 6 km of elevation. We utilize soil data and a digital elevation model to construct isoscapes, delineate catchments for each river sampling location, predict river values assuming spatial uniform integration, and compare our predictions with observed values. Although both compounds generally follow isotopic gradients defined by catchment elevations, the dual isotope and compound-class comparison reveals additional processes. For C30 n-alkanoic acid we find an up to 1km lower-than-expected catchment signal, indicating degradation of upland contributions in transit and replacement with lowland inputs. In contrast, mountain-front river locations are susceptible to upland-biases (up to 1km higher sourcing) in C29 n-alkane sourcing, likely due to enhanced erosion and higher leaf wax stock in Andean soil compared to the lowland, and greater persistence of n-alkanes than n-alkanoic acids. For both compounds, the bias is eliminated with several hundred km of river transit across the floodplain. In one location, we identify significant petrogenic contamination of n-alkanes but not n-alkanoic acids. These results indicate the power in combining dual compound classes and dual isotopes to analyze source-to-sink processes and to evaluate sourcing of river exported plant wax biomarkers.

Multivariate postprocessing techniques for probabilistic hydrological forecasting

NASA Astrophysics Data System (ADS)

Hemri, Stephan; Lisniak, Dmytro; Klein, Bastian

2016-04-01

Hydrologic ensemble forecasts driven by atmospheric ensemble prediction systems need statistical postprocessing in order to account for systematic errors in terms of both mean and spread. Runoff is an inherently multivariate process with typical events lasting from hours in case of floods to weeks or even months in case of droughts. This calls for multivariate postprocessing techniques that yield well calibrated forecasts in univariate terms and ensure a realistic temporal dependence structure at the same time. To this end, the univariate ensemble model output statistics (EMOS; Gneiting et al., 2005) postprocessing method is combined with two different copula approaches that ensure multivariate calibration throughout the entire forecast horizon. These approaches comprise ensemble copula coupling (ECC; Schefzik et al., 2013), which preserves the dependence structure of the raw ensemble, and a Gaussian copula approach (GCA; Pinson and Girard, 2012), which estimates the temporal correlations from training observations. Both methods are tested in a case study covering three subcatchments of the river Rhine that represent different sizes and hydrological regimes: the Upper Rhine up to the gauge Maxau, the river Moselle up to the gauge Trier, and the river Lahn up to the gauge Kalkofen. The results indicate that both ECC and GCA are suitable for modelling the temporal dependences of probabilistic hydrologic forecasts (Hemri et al., 2015). References Gneiting, T., A. E. Raftery, A. H. Westveld, and T. Goldman (2005), Calibrated probabilistic forecasting using ensemble model output statistics and minimum CRPS estimation, Monthly Weather Review, 133(5), 1098-1118, DOI: 10.1175/MWR2904.1. Hemri, S., D. Lisniak, and B. Klein, Multivariate postprocessing techniques for probabilistic hydrological forecasting, Water Resources Research, 51(9), 7436-7451, DOI: 10.1002/2014WR016473. Pinson, P., and R. Girard (2012), Evaluating the quality of scenarios of short-term wind power generation, Applied Energy, 96, 12-20, DOI: 10.1016/j.apenergy.2011.11.004. Schefzik, R., T. L. Thorarinsdottir, and T. Gneiting (2013), Uncertainty quantification in complex simulation models using ensemble copula coupling, Statistical Science, 28, 616-640, DOI: 10.1214/13-STS443.

Laser depth profiling of diffusion and alpha ejection profiles in Durango apatite: testing the fundamental parameters of apatite (U-Th)/He dating

NASA Astrophysics Data System (ADS)

van Soest, M. C.; Monteleone, B. D.; Boyce, J. W.; Hodges, K.

2009-12-01

Since its development (e.g. Zeitler et al., 1987, Lippolt et al., 1994, Farley et al., 1996, Wolf et al., 1996) as a viable low temperature thermochronological method (U-Th)/He dating of apatite has become a popular and widely applied low temperature thermochronometer. The method has been applied with success to a great variety of geological problems, and the fundamental parameters of the method: the bulk diffusion parameters of helium in apatite, and the calculated theoretical helium stopping distance in apatite used to correct the ages for the effects of alpha ejection appear sound. However, the development of the UV laser microprobe technique for the (U-Th)/He method (Boyce et al., 2006) allows for in-situ testing of the helium bulk diffusion parameters (Farley, 2000) and can provide a direct measurement of the alpha ejection distance in apatite. So, with the ultimate goal of further developing the in-situ (U-Th)/He dating method and micro-analytical depth profiling techniques to constrain cooling histories in natural grains, we conducted a helium depth profiling study of induced diffusion and natural alpha ejection profiles in Durango apatite. For the diffusion depth profiling, a Durango crystal was cut in slabs oriented parallel and perpendicular to the crystal c-axis. The slabs were polished and heated using different temperature and time schedules to induce predictable diffusion profiles based on the bulk helium diffusion parameters in apatite. Depth profiling of the 4He diffusion profiles was done using an ArF excimer laser. The measured diffusion depth profiles at 350°, 400°, and 450° C coincide well with the predicted bulk diffusion curves, independent of slab orientation, but the 300° C profiles consistently deviate significantly. The possible cause for this deviation is currently being investigated. Alpha ejection profiling was carried out on crystal margins from two different Durango apatite crystals, several faces from each crystal were analyzed to evaluate the potential effects of crystallographic orientation on alpha ejection. The results from both crystals were very reproducible irrespective of crystal surface used and confirm the findings of Monteleone et al. (2008) that the measured alpha ejection profiles deviate significantly from and are shorter than the calculated theoretical average value. Efforts are currently underway to better constrain the measured alpha ejection distance and measure alpha ejection profiles in apatite crystals other than Durango apatite. References: Boyce, J. et al. (2006) GCA 70, pp. 3031-3039. Farley, K. et al. (1996) GCA 60, pp. 4223-4229. Farley, K. (2006) JGR SE 105, p. 2903-2914. Lippolt, H. et al. (1994) Chem Geol 112, pp. 179-191. Monteleone, B. et al. (2008) Eos Trans AGU, 89 Fall Meeting V53B-2162. Wolf, R. et al. (1996) GCA 60, pp. 4231-4240. Zeitler, P. et al. (1987) GCA 51, pp. 2865-2868.

Optimization of Direct Fibroblast Reprogramming to Cardiomyocytes Using Calcium Activity as a Functional Measure of Success

PubMed Central

Addis, Russell C.; Ifkovits, Jamie L.; Pinto, Filipa; Kellam, Lori D.; Esteso, Paul; Rentschler, Stacey; Christoforou, Nicolas; Epstein, Jonathan A.; Gearhart, John D.

2013-01-01

Direct conversion of fibroblasts to induced cardiomyocytes (iCMs) has great potential for regenerative medicine. Recent publications have reported significant progress, but the evaluation of reprogramming has relied upon non-functional measures such as flow cytometry for cardiomyocyte markers or GFP expression driven by a cardiomyocyte-specific promoter. The issue is one of practicality: the most stringent measures - electrophysiology to detect cell excitation and the presence of spontaneously contracting myocytes - are not readily quantifiable in the large numbers of cells screened in reprogramming experiments. However, excitation and contraction are linked by a third functional characteristic of cardiomyocytes: the rhythmic oscillation of intracellular calcium levels. We set out to optimize direct conversion of fibroblasts to iCMs with a quantifiable calcium reporter to rapidly assess functional transdifferentiation. We constructed a reporter system in which the calcium indicator GCaMP is driven by the cardiomyocyte-specific Troponin T promoter. Using calcium activity as our primary outcome measure, we compared several published combinations of transcription factors along with novel combinations in mouse embryonic fibroblasts. The most effective combination consisted of Hand2, Nkx2.5, Gata4, Mef2c, and Tbx5 (HNGMT). This combination is >50-fold more efficient than GMT alone and produces iCMs with cardiomyocyte marker expression, robust calcium oscillation, and spontaneous beating that persists for weeks following inactivation of reprogramming factors. HNGMT is also significantly more effective than previously published factor combinations for the transdifferentiation of adult mouse cardiac fibroblasts to iCMs. Quantification of calcium function is a convenient and effective means for the identification and evaluation of cardiomyocytes generated by direct reprogramming. Using this stringent outcome measure, we conclude that HNGMT produces iCMs more efficiently than previously published methods. PMID:23591016

Phage Display Breast Carcinoma cDNA Libraries: Isolation of Clones Which Specifically Bind to Membrane Glycoproteins, Mucins, and Endothelial Cell Surface

DTIC Science & Technology

1999-07-01

nutrients and waste and UV 2237 fibrosarcoma sublines (17). Expression of elimination, cell surfaces are also important for the galectin-1, another member of...10B capsid protein. Therefore, this GAG CGG AAA ATG GCA GAC AAT TTT TCG CTC CAT ... vector was chosen to assess the feasibility of phage met Ala Asp

Carbonaceous Material in Extraterrestrial Matter

NASA Astrophysics Data System (ADS)

Martins, Zita

2015-08-01

Comets, asteroids and their fragments (i.e. meteorite, micrometeorites and interplanetary dust particles (IDPs)) are known to contain carbonaceous material. IDPs have ~10% of carbon by mass [1-3], while both micrometeorites and IDPs contain organic molecules. However, it is not certain whether these molecules are indigenous or terrestrial contamination [4-7]. On the other hand, ultra-carbonaceous Antarctic micrometeorites (UCAMMs) contain 50-80% of carbonaceous material, which is one of the highest organic matter contents detected in an extraterrestrial body [8]. Comets also have several extraterrestrial organic molecules [9, 10], including the simplest amino acid glycine [11]. In addition, the impact-shock of a typical comet ice mixture produces several amino acids from simple precursors [12]. Carbonaceous meteorites contain up to 5wt% of organic carbon [13], which is either locked in an insoluble kerogen-like polymer, or in a rich organic inventory of soluble organic compounds [14-16]. Bulk analysis of the meteoritic soluble organic fraction has revealed a high molecular diversity of tens of thousands of different molecular compositions [17]. The analysis of the carbonaceous content of comets, asteroids and their fragments provides a window into the resources delivered to the early Earth.[1] Brownlee (1985) Ann. Rev. Earth and Plan. Sci. 13, 147. [2] Schramm et al. (1989) Meteoritics 24, 99. [3] Messenger (2002) MAPS 37, 1491. [4] Clemett et al. (1993) Science 262, 721. [5] Brinton et al. (1998) OLEB 28, 413. [6] Flynn (2003) GCA 67, 4791. [7] Matrajt et al. (2004) MAPS 39, 1849. [8] Duprat et al. (2010) Science 328, 742-745. [9] Bockelée-Morvan et al. (2004) in: Comets II. pp. 391-423. [10] Mumma and Charnley (2011) ARAA 49, 471. [11] Elsila et al. (2009) MAPS 44, 1323. [12] Martins et al. (2013) Nature Geoscience 6, 1045. [13] Alexander et al. (2013) GCA 123, 244. [14] Cronin and Chang (1993) in: The Chemistry of Life’s Origin. pp. 209-258. [15] Cody and Alexander (2005) GCA 69, 1085. [16] Martins and Sephton (2009) in: Amino acids, peptides and proteins in organic chemistry. pp. 1-42. [17] Schmitt-Kopplin et al. (2010) PNAS 107, 2763.

The Importance of Connexin Hemichannels During Chondroprogenitor Cell Differentiation in Hydrogel Versus Microtissue Culture Models

PubMed Central

Schrobback, Karsten; Klein, Travis Jacob

2015-01-01

Appropriate selection of scaffold architecture is a key challenge in cartilage tissue engineering. Gap junction-mediated intercellular contacts play important roles in precartilage condensation of mesenchymal cells. However, scaffold architecture could potentially restrict cell–cell communication and differentiation. This is particularly important when choosing the appropriate culture platform as well as scaffold-based strategy for clinical translation, that is, hydrogel or microtissues, for investigating differentiation of chondroprogenitor cells in cartilage tissue engineering. We, therefore, studied the influence of gap junction-mediated cell–cell communication on chondrogenesis of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and articular chondrocytes. Expanded human chondrocytes and BM-MSCs were either (re-) differentiated in micromass cell pellets or encapsulated as isolated cells in alginate hydrogels. Samples were treated with and without the gap junction inhibitor 18-α glycyrrhetinic acid (18αGCA). DNA and glycosaminoglycan (GAG) content and gene expression levels (collagen I/II/X, aggrecan, and connexin 43) were quantified at various time points. Protein localization was determined using immunofluorescence, and adenosine-5′-triphosphate (ATP) was measured in conditioned media. While GAG/DNA was higher in alginate compared with pellets for chondrocytes, there were no differences in chondrogenic gene expression between culture models. Gap junction blocking reduced collagen II and extracellular ATP in all chondrocyte cultures and in BM-MSC hydrogels. However, differentiation capacity was not abolished completely by 18αGCA. Connexin 43 levels were high throughout chondrocyte cultures and peaked only later during BM-MSC differentiation, consistent with the delayed response of BM-MSCs to 18αGCA. Alginate hydrogels and microtissues are equally suited culture platforms for the chondrogenic (re-)differentiation of expanded human articular chondrocytes and BM-MSCs. Therefore, reducing direct cell–cell contacts does not affect in vitro chondrogenesis. However, blocking gap junctions compromises cell differentiation, pointing to a prominent role for hemichannel function in this process. Therefore, scaffold design strategies that promote an increasing distance between single chondroprogenitor cells do not restrict their differentiation potential in tissue-engineered constructs. PMID:25693425

Magnesium isotope compositions of Solar System materials determined by double spiking

NASA Astrophysics Data System (ADS)

Hin, R.; Lai, Y. J.; Coath, C.; Elliott, T.

2015-12-01

As a major element, magnesium is of interest for investigating large scale processes governing the formation and evolution of rocky planetary bodies. Determining the Mg isotope composition of the Earth and other planetary bodies has hence been a topic of interest ever since mass-dependent fractionation of 'non-traditional' stable isotopes has been used to study high-temperature processes. Published results, however, suffer from disagreement on the Mg isotope compositions of the Earth and chondrites [1-5], which is attributed to residual matrix effects. Nonetheless, most recent studied have converged towards a homogeneous (chondritic) Mg isotope composition in the Solar System [2-5]. However, in several of the recent studies there is a hint of a systematic difference of about 0.02-0.06‰ in the 26Mg/24Mg isotope compositions of chondrites and Earth. Such difference, however, is only resolvable by taking standard errors, which assumes robust data for homogenous sample sets. The discrepancies between various studies unfortunately undermine the confidence in such robustness and homogeneity. The issues with matrix effects during isotopic analyses can be overcome by using a double spike approach. Such methodology generally requires three isotope ratios to solve for three unknowns, a requirement that cannot be met for Mg. However, using a newly developed approach, we present Mg isotope compositions obtained by critical mixture double spiking. This new approach should allow greater confidence in the robustness of the data and hence enable improvement of. Preliminary data indicate that chondrites have a resolvable ~0.04‰ lighter 26Mg/24Mg than (ultra)mafic rocks from Earth, Mars and the eucrite parent body, which appear indistinguishable from each other. It seems implausible that this difference is caused by magmatic process such as partial melting or crystallisation. More likely, Mg isotopes are fractionated by a non-magmatic process during the formation of planets, e.g. by vapour-condensate fractionation. [1] Wiechert and Halliday, 2007. EPSL 256, 360-371. [2] Bourdon et al., 2010. GCA 74, 5069-5083. [3] Teng et al., 2010. GCA 74, 4150-4166. [4] Chakrabarti and Jacobsen, 2010. EPSl 293, 349-358. [5] Von Strandmann, 2011. GCA 75, 5247-5268.

The importance of connexin hemichannels during chondroprogenitor cell differentiation in hydrogel versus microtissue culture models.

PubMed

Schrobback, Karsten; Klein, Travis Jacob; Woodfield, Tim B F

2015-06-01

Appropriate selection of scaffold architecture is a key challenge in cartilage tissue engineering. Gap junction-mediated intercellular contacts play important roles in precartilage condensation of mesenchymal cells. However, scaffold architecture could potentially restrict cell-cell communication and differentiation. This is particularly important when choosing the appropriate culture platform as well as scaffold-based strategy for clinical translation, that is, hydrogel or microtissues, for investigating differentiation of chondroprogenitor cells in cartilage tissue engineering. We, therefore, studied the influence of gap junction-mediated cell-cell communication on chondrogenesis of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and articular chondrocytes. Expanded human chondrocytes and BM-MSCs were either (re-) differentiated in micromass cell pellets or encapsulated as isolated cells in alginate hydrogels. Samples were treated with and without the gap junction inhibitor 18-α glycyrrhetinic acid (18αGCA). DNA and glycosaminoglycan (GAG) content and gene expression levels (collagen I/II/X, aggrecan, and connexin 43) were quantified at various time points. Protein localization was determined using immunofluorescence, and adenosine-5'-triphosphate (ATP) was measured in conditioned media. While GAG/DNA was higher in alginate compared with pellets for chondrocytes, there were no differences in chondrogenic gene expression between culture models. Gap junction blocking reduced collagen II and extracellular ATP in all chondrocyte cultures and in BM-MSC hydrogels. However, differentiation capacity was not abolished completely by 18αGCA. Connexin 43 levels were high throughout chondrocyte cultures and peaked only later during BM-MSC differentiation, consistent with the delayed response of BM-MSCs to 18αGCA. Alginate hydrogels and microtissues are equally suited culture platforms for the chondrogenic (re-)differentiation of expanded human articular chondrocytes and BM-MSCs. Therefore, reducing direct cell-cell contacts does not affect in vitro chondrogenesis. However, blocking gap junctions compromises cell differentiation, pointing to a prominent role for hemichannel function in this process. Therefore, scaffold design strategies that promote an increasing distance between single chondroprogenitor cells do not restrict their differentiation potential in tissue-engineered constructs.

Pouring 'Cold Water' on Hot Accretion

NASA Astrophysics Data System (ADS)

Rubin, A. E.

1995-09-01

The extensive recrystallization of type-6 OC has been interpreted as having resulted either from prograde thermal metamorphism of initially cold, unequilibrated material [1,2] or from autometamorphism due to slow cooling of material that accreted while still hot (1000-1200 K). Although the physical implausibility of hot accretion has been addressed [3], no comprehensive evaluation has been made of arguments in its favor. As shown below, these arguments are based on incomplete data, flawed experiments or improbable interpretations. Correlation between petrologic type and Ca in low-Ca pyroxene. Models of prograde metamorphism assume that, with increasing temperature, opx acquires Ca at the expense of diopside. Analyses of pyroxene in 10 H chondrites showed no correlation between Ca in pyroxene cores and increasing petrologic type [4], but more extensive data sets show such correlations [1,5,6]. A review of data for 51 OC [7] shows a progressive increase in the Wo content of low-Ca pyroxene with petrologic type: Wo 0.4-1.2 in type-3 and -4; Wo 1.2-1.6 in type-5; and Wo 1.6-2.2 in type-6. Striated opx. Undeformed striated opx were interpreted as having formed from inverted protopyroxene during slow cooling [8]; striated opx from H4 Quenggouk were found to convert into normal opx within 1 week during annealing at 1100 K [9]. Because prograde metamorphism probably lasted ~60 Ma [10], there should be no striated opx remaining in type-4 or -5 OC. However, samples of 99% twinned clinopyroxene (analogous to that in chondrules in type-3 OC) annealed for >3 weeks at <=1250 K exhibited only very minor inversion to opx [11-13]. These experiments are consistent with prograde metamorphism; it seems likely that Quenggouk pyroxene probably had a substantial proportion of opx lamellae to begin with. Spinodal decomposition textures and cooling rates. Spinodal decomposition textures in pyroxene in type 4-5 OC were observed to have the same periodicities as those in type-3 OC [14]; it was concluded that the textures must have formed during cooling after hot accretion. However, because spinodal decomposition textures develop over the temperature range 1400-1100 K [14,15] and type-4 and -5 OC were probably not heated above 1000 K and 1050 K, respectively [16], these textures are probably relicts of chondrule formation. It was also suggested [14] that compositional zoning in pyroxenes indicates that type-3 OC cooled more rapidly than type-4 to -5 OC. However, OC metallographic cooling rates are not correlated with petrologic type [17]. Furthermore, experimental data [13] show that rare thick opx lamellae in H4 Conquista could not have formed during single stage cooling as expected in autometamorphism; a two-stage cooling history involving rapid cooling during chondrule formation followed by parent-body annealing is more plausible. Polycrystalline taenite. Polycrystalline taenite in H/L3 Tieschitz was interpreted as a relict solidification structure that failed to anneal into monocrystalline taenite because of rapid cooling (1700 to 1000 K within days to weeks) [18]; by analogy, it was proposed that all H3-6 chondrites containing polycrystalline taenite cooled rapidly from 1700 K [4], an idea inconsistent with prograde metamorphism. However, cooling rates in equilibrated chondrites that were slow enough to permit significant growth of kamacite would erase prior solidification zoning in taenite by solid-state diffusion [19,20]. This hypothesis, confirmed by computer modeling [21], invalidates the assumption that equilibrated OC containing polycrystalline taenite cooled rapidly. Polycrystalline taenite is most likely a pre-metamorphic relict. Heterogeneous metal grains. Compositionally and texturally heterogeneous metal grains in L6 Bruderheim are unlikely to have survived solid-state diffusion during prograde metamorphism [22]; these authors favored hot accretion followed by low-temperature annealing. However, Bruderheim is a fragmental breccia of shock stage S4 [23] containing partly melted metal grains and opaque veins; heterogeneities in metallic Fe-Ni grains are due to post-metamorphic shock. Misshapen chondrules. A small proportion of chondrules in Tieschitz are non-spherical and seem to have molded themselves around one another while they were at least partly molten, possibly on the surface of a hot asteroid [24]. However, it is now clear that these conjoined objects are adhering or enveloping compound chondrules that fused in the nebula [25]; most are probably siblings that collided shortly after forming in the same heating event. Objects adjacent to the compound chondrules are separated by intervening matrix material; because matrix material is fine grained, porous, highly disequilibrated and unmelted [26,27], any complementarity in shape between adjacent objects and compound chondrules is either due to coincidence or jostling during chondrite compaction. Natural remanent magnetization (NRM). The orientations of the stable NRM in OC were found to be random at scales of ~1 mm3 [28]. Because metamorphic heating would erase the random magnetization, these authors opted for hot accretion. However, most OC appear to be fragmental breccias that contain scattered metal and silicate grains of aberrant compositions that were incorporated into their hosts after metamorphic equilibration [29,30]; by analogy to some CM chondrites which contain mm-size clasts that experienced different degrees of aqueous alteration [31], it is plausible that OC are also brecciated on mm-size scales. Such fine-scale brecciation could account for the random orientations of the stable NRM. References: [1] Dodd R. T. (1969) GCA, 33, 161-203. [2] McSween H. Y. et al. (1988) in Meteorites and the Early Solar System, 102-113, Univ. of Arizona, Tucson. [3] Haack H. et al. (1992) GRL, 19, 2235-2238. [4] Hutchison R. et al. (1980) Nature, 287, 787-790. [5] Keil K. and Fredriksson K. (1964) JGR, 69, 3487-3515. [6] Heyse J. V. (1978) EPSL, 40, 365-381. [7] Scott E. R. D. et al. (1986) Proc. LPSC 17th, in JGR, 91, E115-E123. [8] Ashworth J. R. (1980) EPSL, 46, 167-177. [9] Ashworth J. R. et al. (1984) Nature, 308, 259-261. [10] G"pel C. et al. (1994) EPSL, 121, 153-171. [11] Jones R. H. and Brearley A. J. (1988) Meteoritics, 23, 277. [12] Brearley A. J. and Jones R. H. (1988) Eos Trans. AGU, 69, 1506. [13] Brearley A. J. and Jones R. H. (1993) LPS XXIV, 185-186. [14] Watanabe S. et al. (1985) EPSL, 72, 87-98. [15] Robinson P. et al. (1977) Am. Mineral., 62, 857-873. [16] Dodd R. T. (1981) Meteorites: A Petrologic-Chemical Synthesis, Cambridge. [17] Taylor G. J. (1987) Icarus, 69, 1-13. [18] Bevan A. W. R. and Axon H. J. (1980) EPSL, 47, 353-360. [19] Scott E. R. D. and Rajan R. S. (1981) GCA, 45, 53-67. [20] Scott E. R. D. and Rajan R. S. (1981) GCA, 45, 1959. [21] Willis J. and Goldstein J. I. (1981) Nature, 293, 126-127. [22] Smith D. G. W. and Launspach S. (1991) EPSL, 102, 79-93. [23] St"ffler D. et al. (1991) GCA, 55, 3845-3867. [24] Hutchison R. et al. (1979) Nature, 280, 116-119. [25] Wasson J. T. et al. (1995) GCA, 59, 1847-1869. [26] Scott E. R. D. et al. (1984) GCA, 48, 1741-1757. [27] Nagahara H. (1984) GCA, 48, 2581-2595. [28] Morden S. J. and Collinson D. W. (1992) EPSL, 109, 185-204. [29] Scott E. R. D. et al. (1985) Proc. LPSC 16th, in JGR, 90, D137-D148. [30] Rubin A. E. (1990) GCA, 54, 1217-1232. [31] Rubin A. E. and Wasson J. T. (1986) GCA, 50, 307-315.

Environmental Assessment for Conventional Strike Missile Demonstration

DTIC Science & Technology

2010-08-01

Minotaur IV Lite, eight nickel- cadmium batteries are carried in the GCA. The battery weights range from 3 to 12 lb (1.4 to 5.4 kg) each. Launches of...would not present any toxicity concerns. Although the nickel- cadmium batteries carried onboard the launch vehicle would be spent (discharged) by the...Systems Engineering, University of Alabama in Huntsville BS, Medical Technology, University of Tennessee BS, Biology, Indiana State University 21

New Transgenic Mouse Lines for Selectively Targeting Astrocytes and Studying Calcium Signals in Astrocyte Processes In Situ and In Vivo.

PubMed

Srinivasan, Rahul; Lu, Tsai-Yi; Chai, Hua; Xu, Ji; Huang, Ben S; Golshani, Peyman; Coppola, Giovanni; Khakh, Baljit S

2016-12-21

Astrocytes exist throughout the nervous system and are proposed to affect neural circuits and behavior. However, studying astrocytes has proven difficult because of the lack of tools permitting astrocyte-selective genetic manipulations. Here, we report the generation of Aldh1l1-Cre/ERT2 transgenic mice to selectively target astrocytes in vivo. We characterized Aldh1l1-Cre/ERT2 mice using imaging, immunohistochemistry, AAV-FLEX-GFP microinjections, and crosses to RiboTag, Ai95, and new Cre-dependent membrane-tethered Lck-GCaMP6f knockin mice that we also generated. Two to three weeks after tamoxifen induction, Aldh1l1-Cre/ERT2 selectively targeted essentially all adult (P80) brain astrocytes with no detectable neuronal contamination, resulting in expression of cytosolic and Lck-GCaMP6f, and permitting subcellular astrocyte calcium imaging during startle responses in vivo. Crosses with RiboTag mice allowed sequencing of actively translated mRNAs and determination of the adult cortical astrocyte transcriptome. Thus, we provide well-characterized, easy-to-use resources with which to selectively study astrocytes in situ and in vivo in multiple experimental scenarios. Copyright © 2016 Elsevier Inc. All rights reserved.

Task-dependent individual differences in prefrontal connectivity.

PubMed

Biswal, Bharat B; Eldreth, Dana A; Motes, Michael A; Rypma, Bart

2010-09-01

Recent advances in neuroimaging have permitted testing of hypotheses regarding the neural bases of individual differences, but this burgeoning literature has been characterized by inconsistent results. To test the hypothesis that differences in task demands could contribute to between-study variability in brain-behavior relationships, we had participants perform 2 tasks that varied in the extent of cognitive involvement. We examined connectivity between brain regions during a low-demand vigilance task and a higher-demand digit-symbol visual search task using Granger causality analysis (GCA). Our results showed 1) Significant differences in numbers of frontoparietal connections between low- and high-demand tasks 2) that GCA can detect activity changes that correspond with task-demand changes, and 3) faster participants showed more vigilance-related activity than slower participants, but less visual-search activity. These results suggest that relatively low-demand cognitive performance depends on spontaneous bidirectionally fluctuating network activity, whereas high-demand performance depends on a limited, unidirectional network. The nature of brain-behavior relationships may vary depending on the extent of cognitive demand. High-demand network activity may reflect the extent to which individuals require top-down executive guidance of behavior for successful task performance. Low-demand network activity may reflect task- and performance monitoring that minimizes executive requirements for guidance of behavior.

Task-Dependent Individual Differences in Prefrontal Connectivity

PubMed Central

Biswal, Bharat B.; Eldreth, Dana A.; Motes, Michael A.

2010-01-01

Recent advances in neuroimaging have permitted testing of hypotheses regarding the neural bases of individual differences, but this burgeoning literature has been characterized by inconsistent results. To test the hypothesis that differences in task demands could contribute to between-study variability in brain-behavior relationships, we had participants perform 2 tasks that varied in the extent of cognitive involvement. We examined connectivity between brain regions during a low-demand vigilance task and a higher-demand digit–symbol visual search task using Granger causality analysis (GCA). Our results showed 1) Significant differences in numbers of frontoparietal connections between low- and high-demand tasks 2) that GCA can detect activity changes that correspond with task-demand changes, and 3) faster participants showed more vigilance-related activity than slower participants, but less visual-search activity. These results suggest that relatively low-demand cognitive performance depends on spontaneous bidirectionally fluctuating network activity, whereas high-demand performance depends on a limited, unidirectional network. The nature of brain-behavior relationships may vary depending on the extent of cognitive demand. High-demand network activity may reflect the extent to which individuals require top-down executive guidance of behavior for successful task performance. Low-demand network activity may reflect task- and performance monitoring that minimizes executive requirements for guidance of behavior. PMID:20064942

Automated Video-Based Analysis of Contractility and Calcium Flux in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Cultured over Different Spatial Scales

PubMed Central

Huebsch, Nathaniel; Loskill, Peter; Mandegar, Mohammad A.; Marks, Natalie C.; Sheehan, Alice S.; Ma, Zhen; Mathur, Anurag; Nguyen, Trieu N.; Yoo, Jennie C.; Judge, Luke M.; Spencer, C. Ian; Chukka, Anand C.; Russell, Caitlin R.; So, Po-Lin

2015-01-01

Contractile motion is the simplest metric of cardiomyocyte health in vitro, but unbiased quantification is challenging. We describe a rapid automated method, requiring only standard video microscopy, to analyze the contractility of human-induced pluripotent stem cell-derived cardiomyocytes (iPS-CM). New algorithms for generating and filtering motion vectors combined with a newly developed isogenic iPSC line harboring genetically encoded calcium indicator, GCaMP6f, allow simultaneous user-independent measurement and analysis of the coupling between calcium flux and contractility. The relative performance of these algorithms, in terms of improving signal to noise, was tested. Applying these algorithms allowed analysis of contractility in iPS-CM cultured over multiple spatial scales from single cells to three-dimensional constructs. This open source software was validated with analysis of isoproterenol response in these cells, and can be applied in future studies comparing the drug responsiveness of iPS-CM cultured in different microenvironments in the context of tissue engineering. PMID:25333967

The effects of serpentinization on Mg isotopes in Mid-Atlantic ridge peridotite

NASA Astrophysics Data System (ADS)

Wimpenny, J.; Harvey, J.; Yin, Q.

2012-12-01

The magnesium isotope composition of the Earth's mantle [1], and bulk estimates for upper crustal rocks [2] overlap with values obtained from chondritic meteorites [1], suggesting broad scale homogeneity of δ26Mg on Earth. By way of contrast, weathering of continental crust results in significant fractionation of Mg isotopes [3]. Negative δ26Mg in riverine and groundwater fluxes suggest that the lighter isotopes of Mg are preferentially removed in fluid during partial weathering, leaving a heavy δ26Mg residuum [4]. Thus, riverine fluxes to the ocean result in a marine reservoir with a δ26Mg = -0.82 ± 0.01 [5], significantly lighter than that of fresh mantle material and its derivatives [1]. Abyssal peridotites recovered from Ocean Drilling Program Leg 209 display a wide range of bulk-rock compositions and have been demonstrated to have interacted with a number of low and high temperature fluids [6]. Peridotite from Hole 1274a has been variably serpentinized at low (c. 200 oC) temperatures. Serpentinized samples from Hole 1268a, have also interacted with a higher temperature fluid (c. 350 oC) with a low Mg/Si ratio resulting in abundant talc formation [6]. Serpentinites contain high concentrations of Mg and are abundantly exposed at the seafloor at slow and ultra-slow oceanic ridges [7,8]. Because peridotites are thought to be a source of Mg to seawater [9] any fractionation of Mg isotopes that accompanies serpentinization will have implications for the composition of Mg in seawater. The δ26Mg of samples from 1274a are similar to primary upper crustal rocks, (UCC δ26Mg = -0.22 ± 0.04 [2]). However, samples from 1268a have fractionated δ26Mg values that are generally enriched in isotopically heavy Mg relative to the UCC, ranging from -0.25 to -0.02‰. These results suggest that serpentinization itself does not cause fractionation of Mg, but that later formation of talc is associated with the preferential retention of isotopically heavy Mg, consistent with secondary silicates formed during continental weathering [e.g. 3]. Mass balance requires that the talc-altered serpentinite must be complimented by an isotopically light component. It seems most likely that this isotopically light Mg will be transferred and mixed into ambient temperature seawater. The impact of this transfer will be dependent on the size of the Mg exchange between peridotite and seawater and the fractionation factor associated with talc alteration. Our data suggest that this would input Mg into seawater that is isotopically light relative to the altered peridotite. [1] Pogge von Strandmann et al., (2011) GCA 75, 5247-5268. [2] Li et al. (2010) GCA 74, 6867-6884. [3] Tipper et al., (2006) EPSL 247, 267-279. [4] Wimpenny et al., (2010) GCA 74, 5259-5279. [5] Foster et al., (2010) Geochem. Geophys. Geosys. 11, doi:10.1029/2010GC003201. [6] Bach et al., (2004) Geochem. Geophys. Geosys. 5, doi:10.1029/2004GC000744. [7] Cannat et al., (1997) Tectonophys. 279, 193-213. [8] Jokat et al., (2003) Nature 423, 962-965. [9] Snow & Dick (1995) GCA, 59, 4219-4235.

Intravesical NGF Antisense Therapy Using Lipid Nanoparticle for Interstitial Cystitis

DTIC Science & Technology

2014-10-01

sequences used for real-time PCR were the following: 5’- AGT AAC TGC CAG GAG CTG GA-3’ (forward) and 5’- GTG TCA TTC TGC CCA TTG TG-3’ (reverse) for...rat TRPV1 and 5’- GGC CAA AAG GGT CAT CAT CT-3’ (forward) and 5’- GTG ATG GCA TGG ACT GTG GT-3’ (reverse) for rat GAPDH, which is a house keeping

Identification and Characterization of Ovarian Carcinoma Peptide Epitopes Recognized by Cylotoxic T Lymphocytes

DTIC Science & Technology

2008-11-01

CTC CCA CAG TGC CCC AGG TTA GAA CGG TCA GCA GAA TAG-2a 62 528 AGC GGC GGG CTG AAG GA GAG GGT AGG GTG GTC ATT GTG TCA TAG-2b 62 401 AGC GGC GGG CTG AAG...64:388–393 66. Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC

Structural relaxation of vitreous albite near Tg and implications for transport properties of the supercooled liquid at high pressure

NASA Astrophysics Data System (ADS)

Gaudio, S. J.; Lesher, C. E.

2012-12-01

We estimate the glass transition temperature, Tg, for vitreous/amorphous albite between 0 and 7.7 GPa by tracking the progress of densification following high-temperature annealing experiments with run durations equal to 5τ (when τ=100 s). Tg decreases by 54 K/GPa up to 2.6 GPa, and thereafter shows a weak negative pressure dependence. This behavior mimics the negative pressure dependence of viscosity of albite liquid shown by [1]; however, we do not find a change in the sign of ∂Tg/∂P at least up to 7.7 GPa as reported in some isothermal ∂η/∂P, and ∂DO/∂P data sets. Our high field (21.8 T) 27Al MAS NMR measurements of recovered glasses rapidly quenched from super-Tg conditions possess trace amounts of high coordinated Al at 2.6 GPa and only ˜17% by 5.5 GPa. This suggests that the decrease in Tg (and viscosity at low temperature) results dominantly from topological rearrangement of the supercooled melt structure and not changes to Al or Si coordination number and connectivity of the network. In fact, at Tg from 0 to 8 GPa, the XNBO, or network connectivity, is unchanged [2] and at 7.7 GPa, we find the proportion of high coordinated Al is still ˜35%. Convergence in the timescales of relaxation at Tg(P) and the onset of Na mobility to 6 GPa documented by high-pressure electrical conductivity measurements [3] implies that the fragility of albite melt increases with pressure up to ˜4-5 GPa, without changing the effective polymerization of the melt. In contrast, fragility appears to decrease with pressure in partially depolymerized silicate melts. Such differences in fragility can be used for extrapolation of activation energy based models for viscous flow to high pressure. [1] Kushiro, 1978, EPSL, 41; Brearley et al., 1986, GCA, 50; Brearley and Montana, 1989, GCA, 53; Poe et al., 1997, Science, 276; Suzuki et al., 2002, Phys. Chem. Miner., 29; Funakoshi et al., 2002, J. Phys.: Condens. Matter., 14; Behrens and Schulze, 2003, Am. Min., 88. [2] Lee et al. 2004, GCA, 68; [3] Bagdassarov et al., 2004, Phys. Chem. Glasses, 45.

Investigating Planetary Volatile Accretion Mechanisms Using the Halogens

NASA Astrophysics Data System (ADS)

Ballentine, C. J.; Clay, P. L.; Burgess, R.; Busemann, H.; Ruzié, L.; Joachim, B.; Day, J. M.

2014-12-01

Depletion of the volatile elements in the Earth relative to the CI chondrites is roughly correlated with volatility, or decreasing condensation temperature. For the heavy halogen group elements (Cl, Br and I), volatility alone does not account for their apparent depletion, which early data has suggested is far greater than predicted [1-2]. Such depletion has been used to argue for the preferential loss of halogens by, amongst other processes, impact-driven erosive loss from Earth's surface [2]. Little consensus exists as to why the halogens should exhibit such preferential behavior during accretionary processes. Early efforts to constrain halogen abundance and understand their behavior in both Earth and planetary materials [3-6] have been hampered by their typically low abundance (ppb level) in most geologic materials. We present the results of halogen analysis of 23 chondrite samples, selected to represent diverse groups and petrologic type. Halogen abundances were measured by neutron irradiation noble gas mass spectrometry (NI-NGMS). Significant concentration heterogeneity is observed within some samples. However, a single Br/Cl and I/Cl ratio of 1.9 ± 0.2 (x 10-3) and 335 ± 10 (x 10-6) can be defined for carbonaceous chondrites with a good correlation between Br and Cl (R2 = 0.97) and between I and Cl (R2 = 0.84). Ratios of I/Cl overlap with terrestrial estimates of Bulk Silicate Earth and Mid Ocean Ridge Basalts. Similarly, good correlations are derived for enstatite (E) chondrites and a sulfide- and halogen- rich subset of E-chondrites. Chlorine abundances of CI (Orgueil) in this study are lower by factor of ~ 3 than the value of ~ 700 ppm Cl (compilation in [1]). Our results are similar to early discarded low values for Ivuna and Orgueil from [5,6] and agree more closely with values for CM chondrites. Halogens may not be as depleted in Earth as previously suggested, or a high degree of heterogeneity in the abundance of these volatile elements in carbonaceous chondrites should be considered when we assess Earth's halogen abundance relative to CI. [1] Lodders (2003) Astr J 591:1220-47. [2] Sharp et al. (2013) EPSL 369/70: 71-7. [3] Dreibus et al. (1979) Phys Chem Earth 11:33-8. [4] Goles et al. (1967) GCA 31: 1771-7. [5] Reed and Allen (1966) GCA 30: 779-800. [6] Greenland & Lovering (1965) GCA 29: 821-58.

Silicon Isotope Geochemistry of Ocean Island Basalts: Mantle Heterogeneities and Contribution of Recycled Oceanic Crust and Lithosphere

NASA Astrophysics Data System (ADS)

Pringle, E. A.; Moynier, F.; Savage, P. S.; Jackson, M. G.; Moreira, M. A.; Day, J. M.

2015-12-01

The study of Silicon (Si) isotopes in Ocean Island Basalts (OIB) has the potential to elucidate between possible heterogeneities in the mantle. Relatively large (~several per mil per atomic mass unit) Si isotope fractionation occurs in low-temperature environments during biochemical and geochemical precipitation of dissolved Si, where the precipitate is preferentially enriched in the lighter isotopes [1]. In contrast, only a limited range (~tenths of a per mil) of Si isotope fractionation has been observed in high-temperature igneous processes [2]. Therefore, Si isotopes may be useful as tracers for the presence of crustal material (derived from low-temperature surface processes) in OIB source regions in a manner similar to more conventional stable isotope systems, such as O. Here we present the first comprehensive set of high-precision Si isotope data obtained by MC-ICP-MS for a diverse suite of OIBs, including new data for the Canary Islands. Samples represent the Pacific, Atlantic, and Indian Ocean basins and include representative end-members for the EM-1, EM-2, and HIMU mantle components. Average δ30Si values for OIBs representing the EM-1 (-0.32 ± 0.06‰, 2 sd), EM-2 (-0.30 ± 0.01‰, 2 sd), and HIMU (-0.34 ± 0.09‰, 2 sd) mantle components are all in general agreement with previous estimates for the δ30Si value of Bulk Silicate Earth [3]. However, small systematic variations are present; HIMU (Mangaia, Cape Verde, La Palma) and Iceland OIBs are enriched in the lighter isotopes of Si (δ30Si values lower than MORB). Further, the difference in Si isotope composition between La Palma and El Heirro (Canary Islands) has previously been observed for O isotopes [4], suggesting a relationship between the Si and O isotope mantle systematics. The Si isotope variations among OIBs may be explained by the sampling of a primitive mantle reservoir enriched in the light isotopes of Si, as suggested by [5], but most likely reflects the incorporation of recycled altered oceanic crust and lithosphere in the plume source. References: [1] Ziegler et al., GCA 2005 [2] Savage et al., GCA 2011 [3] Savage et al., EPSL 2010 [4] Day et al., Geology 2009 [5] Huang et al., GCA 2014

Renal atrial natriuretic factor receptors in hamster cardiomyopathy.

PubMed

Mukaddam-Daher, S; Jankowski, M; Dam, T V; Quillen, E W; Gutkowska, J

1995-12-01

Hamsters with cardiomyopathy (CMO), an experimental model of congestive heart failure, display stimulated renin-angiotensin-aldosterone and enhanced sympathetic nervous activity, all factors that lead to sodium retention, volume expansion and subsequent elevation of plasma atrial natriuretic factor (ANF) by the cardiac atria. However, sodium and water retention persist in CMO, indicating hyporesponsiveness to endogenous ANF. These studies were undertaken to fully characterize renal ANF receptor subtypes in normal hamsters and to evaluate whether alterations in renal ANF receptors may contribute to renal resistance to ANF in cardiomyopathy. Transcripts of the guanylyl cyclase-A (GC-A) and guanylyl cyclase B (GC-B) receptors were detected by quantitative polymerase chain reaction (PCR) in renal cortex, and outer and inner medullas. Compared to normal controls, the cardiomyopathic hamster's GC-A mRNA was similar in cortex but significantly increased in outer and inner medulla. Levels of GC-B mRNA were not altered by the disease. On the other hand, competitive binding studies, autoradiography, and affinity cross-linking demonstrated the absence of functional GC-B receptors in the kidney glomeruli and inner medulla. Also, C-type natriuretic peptide (CNP), the natural ligand for the GC-B receptors, failed to stimulate glomerular production of its second messenger cGMP. In CMO, sodium and water excretion were significantly reduced despite elevated plasma ANF (50.5 +/- 11.1 vs. 309.4 +/- 32.6 pg/ml, P < 0.001). Competitive binding studies of renal glomerular ANF receptors revealed no change in total receptor density, Bmax (369.6 +/- 27.4 vs. 282.8 +/- 26.2 fmol/mg protein), nor in dissociation constant, Kd (647.4 +/- 79.4 vs. 648.5 +/- 22.9 pM). Also, ANF-C receptor density (254.3 +/- 24.8 vs. 233.8 +/- 23.5 fmol/mg protein), nor affinity were affected by heart failure. Inner medullary receptors were exclusively of the GC-A subtype with Bmax (153.2 +/- 26.4 vs. 134.5 +/- 21.2 fmol/mg protein) and Kd (395.7 +/- 148.0 vs. 285.8 +/- 45.0 pM) not altered by cardiomyopathy. The increase in ANF-stimulated glomerular cGMP production was similar in normal and CMO hamsters (94- vs. 75-fold). These results demonstrate that renal ANF receptors do not contribute to the attenuated renal responses to ANF in hamster cardiomyopathy.

Experimental Determination of Carbon Isotope Fractionation in C-O-H-Fluids and the Carbonate-melt - Graphite System at High Temperatures

NASA Astrophysics Data System (ADS)

Kueter, N.; Schmidt, M. W.; Lilley, M. D.; Bernasconi, S. M.

2017-12-01

The understanding of deep-earth carbon fluxes depends greatly on the investigation of carbon isotope systematics in C-O-H-fluids and carbon minerals, such as graphite and diamond (C0). The isotope fractionation factors between the different C-phases and species (in e.g. a fluid) thus govern the observed isotope fractionation patterns. C-isotope fractionation factors relevant for high temperatures are mainly derived from theoretical calculations [e.g. 1,2,3] and, with few exceptions, lack experimental determinations [e.g. 4]. Hundreds of own experiments aimed at equilibrating elemental carbon (C0, graphite/diamond) with C-O-H-fluids demonstrate that kinetics reigns as no system would be closed for H on time scales and temperatures allowing for graphite to equilibrate. To overcome this problem, we performed two studies to determine the C-isotope fractionation in 1) the CO2-CO-CH4 system and 2) the carbonate-melt - graphite system. Equilibrium C-isotope fractionation factors were obtained for CO2 - CO and CH4 - CO pairs (600 - 1200°C) and graphite - Na2CO3/CaCO3melt (900 - 1500°C). Combined with the already available fractionation data for the CaCO3-CO2 pair (400-950°C) from Chacko et al. [4], we determined experimentally based C-isotope fractionation factors for C0 - CH4 and CO2 - C0 pairs by 1) Δ13CCO2-graphite = Δ13CCO2-carbonate + Δ13CCarbonate-graphite and 2) Δ13Cgraphite-CH4 = Δ13CCO2-CH4 - Δ13CCO2-graphite . Current calculated fractionation factors relevant for mantle temperatures (1100 - 1500°C) suggest C-isotope partitioning in the CO2 - C0 pair on the order of 4.2 to 2.4‰, about 2‰ less than predicted by theoretically derived factors [3]. In contrast, our calculations suggest fractionation of about 1.4 to 1.1‰ for the C0 - CH4 pair, about 1‰ higher than expected by theory [3]. [1] Richet et al. (1977) Ann. Rev. Earth Planet. Sci.; [2] Polyakov & Kharlashina (1995) GCA; [3] Bottinga (1969) GCA; [4] Chacko et al. (2001) Rev Mineral Geochem

Risky Business: Reducing Moral Hazard in Airlift Operations

DTIC Science & Technology

2012-06-01

as to use a weather balloon to mark one of Dien Bien Phu’s drop zones in hopes of making drop operations viable when airland operations were not. In...casualties (killed, wounded, missing) of just over 7,000 and probably over 9,000 taken captive at the end of the battle with the odds stacked against...tethered weather balloon to guide their drops when they could not see the drop zone. Using the Ground-Controlled Approach (GCA) radar, personnel

Use of Genetically-encoded Calcium Indicators for Live Cell Calcium Imaging and Localization in Virus-infected Cells

PubMed Central

Perry, Jacob L.; Ramachandran, Nina K.; Utama, Budi; Hyser, Joseph M.

2015-01-01

Calcium signaling is a ubiquitous and versatile process involved in nearly every cellular process, and exploitation of host calcium signals is a common strategy used by viruses to facilitate replication and cause disease. Small molecule fluorescent calcium dyes have been used by many to examine changes in host cell calcium signaling and calcium channel activation during virus infections, but disadvantages of these dyes, including poor loading and poor long-term retention, complicate analysis of calcium imaging in virus-infected cells due to changes in cell physiology and membrane integrity. The recent expansion of genetically-encoded calcium indicators (GECIs), including blue and red-shifted color variants and variants with calcium affinities appropriate for calcium storage organelles like the endoplasmic reticulum (ER), make the use of GECIs an attractive alternative for calcium imaging in the context of virus infections. Here we describe the development and testing of cell lines stably expressing both green cytoplasmic (GCaMP5G and GCaMP6s) and red ER-targeted (RCEPIAer) GECIs. Using three viruses (rotavirus, poliovirus and respiratory syncytial virus) previously shown to disrupt host calcium homeostasis, we show the GECI cell lines can be used to detect simultaneous cytoplasmic and ER calcium signals. Further, we demonstrate the GECI expression has sufficient stability to enable long-term confocal imaging of both cytoplasmic and ER calcium during the course of virus infections. PMID:26344758

Characterization and distribution of natriuretic peptide receptors in the rat uterus.

PubMed

Dos Reis, A M; Fujio, N; Dam, T V; Mukaddam-Daher, S; Jankowski, M; Tremblay, J; Gutkowska, J

1995-10-01

Atrial natriuretic peptide (ANP) receptors were characterized in rat uterus. The binding of [125I]ANP to uterine membranes was completely competed for by increasing concentrations of unlabeled ANP (Kd = 0.39 nM) and brain natriuretic peptide (Kd = 1.24 nM) and partially by C-type natriuretic peptide (CNP; Kd = 80.4 nM), but not by C-ANF. Also, [125I]Tyr-CNP bound to uterine membranes was completely competed by unlabeled CNP (Kd = 1.12 nM). Cross-linking of [125I]ANP to uterine membranes revealed the presence of one band of 130 kilodaltons, corresponding to the guanylyl cyclase (GC-A and/or GC-B) subtypes of natriuretic peptide receptors. The presence of messenger RNA coding for genes of both GC-A and GC-B receptors was shown by quantitative reverse transcriptase polymerase chain reaction. Furthermore, ANP and, to a lesser degree, CNP stimulated the production of cGMP in rat uterus. Autoradiographic studies localized the highest binding of [125I]ANP in the endometrium, whereas [125I]Tyr-CNP binding was distributed in the endometrium as well as in the myometrium. These results demonstrate that rat uterine ANP receptors are of the guanylyl cyclase-coupled subtypes. The uterus is a target of natriuretic peptides where ANP induces its biological effects through the production of cGMP.

Optimization of direct fibroblast reprogramming to cardiomyocytes using calcium activity as a functional measure of success.

PubMed

Addis, Russell C; Ifkovits, Jamie L; Pinto, Filipa; Kellam, Lori D; Esteso, Paul; Rentschler, Stacey; Christoforou, Nicolas; Epstein, Jonathan A; Gearhart, John D

2013-07-01

Direct conversion of fibroblasts to induced cardiomyocytes (iCMs) has great potential for regenerative medicine. Recent publications have reported significant progress, but the evaluation of reprogramming has relied upon non-functional measures such as flow cytometry for cardiomyocyte markers or GFP expression driven by a cardiomyocyte-specific promoter. The issue is one of practicality: the most stringent measures - electrophysiology to detect cell excitation and the presence of spontaneously contracting myocytes - are not readily quantifiable in the large numbers of cells screened in reprogramming experiments. However, excitation and contraction are linked by a third functional characteristic of cardiomyocytes: the rhythmic oscillation of intracellular calcium levels. We set out to optimize direct conversion of fibroblasts to iCMs with a quantifiable calcium reporter to rapidly assess functional transdifferentiation. We constructed a reporter system in which the calcium indicator GCaMP is driven by the cardiomyocyte-specific Troponin T promoter. Using calcium activity as our primary outcome measure, we compared several published combinations of transcription factors along with novel combinations in mouse embryonic fibroblasts. The most effective combination consisted of Hand2, Nkx2.5, Gata4, Mef2c, and Tbx5 (HNGMT). This combination is >50-fold more efficient than GMT alone and produces iCMs with cardiomyocyte marker expression, robust calcium oscillation, and spontaneous beating that persist for weeks following inactivation of reprogramming factors. HNGMT is also significantly more effective than previously published factor combinations for the transdifferentiation of adult mouse cardiac fibroblasts to iCMs. Quantification of calcium function is a convenient and effective means for the identification and evaluation of cardiomyocytes generated by direct reprogramming. Using this stringent outcome measure, we conclude that HNGMT produces iCMs more efficiently than previously published methods. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Correlation of 150-mm silicon wafer site flatness with stepper performance for deep submicron applications

NASA Astrophysics Data System (ADS)

Huff, Howard R.; Vigil, Joseph C.; Kuyel, Birol; Chan, David Y.; Nguyen, Long P.

1992-06-01

An experimental study was conducted to correlate wafer site flatness SFQD with stepper performance for half-micron lines and spaces. CD measurements were taken on wafers patterned on both GCA pre-production XLS i-line and SVGL Micrascan-90 DUV steppers as well as focus measurements on the Micrascan-90. Wafer site flatness SFQD less than 0.3 micrometers was observed to be a sufficiently small variable in CD non-uniformities for these initial half-micron stepper applications.

OSA Proceedings of the Topical Meeting on Soft-X-Ray Projection Lithography Held in Monterey, California on 10-12 April 1991. Volume 12

DTIC Science & Technology

1992-05-22

Carbide because of its high thermal the mirror on its backside or edge. Shott Zerodur conductivity. Edge cooling causes a larger exceeded the limit by about...Characterization Angstrom-level noncontact profiling of mirrors for soft x-ray lithography............ 134 Paul Glenn Nonspecular Scattering from X-Ray...structed by patterning a Mo/Si Tropel Division of GCA Corporation. multilayer coated silicon wafer. The mirrors were coated at AT&T Bell The multilayer

Identifying Molecular Regulators of Neuronal Functions Affected in the Movement Disorder Dystonia

DTIC Science & Technology

2015-08-01

GC-3’ (forward), 5’-CGT GTG GCT GTT GGG GTT GTT GCT GAG GTA-3’ (reverse) for the 498-bp amplicon, 5’-CAC CCT ATC AGG GGA GGA CAA CTT TCG-3’ (forward...3’ (reverse) for the 983- bp amplicon, and 5’-CAC CCT ATC AGG GGA GGA CAA CTT TCG-3’ (forward), 5’-ACA GTG TAG TAA GGC AAA GCA AGG AG-3’ (reverse) for

Hyaluronan-Based Therapy for Metastatic Prostate Cancer

DTIC Science & Technology

2016-09-01

forward 5′-TGT GAC TTT GGT TGT TCC GTT GC-3′ and reverse 5′-ACC TGA GCC GAT GCA ACA ACA G-3′; DR5, forward 5′- AAG ACC CTT GTG CTC GTT GT-3′ and...reverse 5′-AGG TGG ACA CAA TCC CTC TG-3′; actin, forward 5′- TCC CTG GAG AAG AGC TAC GA-3′ and reverse 5′-AGC ACT GTG TTG GCG TAC AG-3′. 2.2.5. Death

Deep brain optical measurements of cell type-specific neural activity in behaving mice.

PubMed

Cui, Guohong; Jun, Sang Beom; Jin, Xin; Luo, Guoxiang; Pham, Michael D; Lovinger, David M; Vogel, Steven S; Costa, Rui M

2014-01-01

Recent advances in genetically encoded fluorescent sensors enable the monitoring of cellular events from genetically defined groups of neurons in vivo. In this protocol, we describe how to use a time-correlated single-photon counting (TCSPC)-based fiber optics system to measure the intensity, emission spectra and lifetime of fluorescent biosensors expressed in deep brain structures in freely moving mice. When combined with Cre-dependent selective expression of genetically encoded Ca(2+) indicators (GECIs), this system can be used to measure the average neural activity from a specific population of cells in mice performing complex behavioral tasks. As an example, we used viral expression of GCaMPs in striatal projection neurons (SPNs) and recorded the fluorescence changes associated with calcium spikes from mice performing a lever-pressing operant task. The whole procedure, consisting of virus injection, behavior training and optical recording, takes 3-4 weeks to complete. With minor adaptations, this protocol can also be applied to recording cellular events from other cell types in deep brain regions, such as dopaminergic neurons in the ventral tegmental area. The simultaneously recorded fluorescence signals and behavior events can be used to explore the relationship between the neural activity of specific brain circuits and behavior.

In vivo wide-field calcium imaging of mouse thalamocortical synapses with an 8 K ultra-high-definition camera.

PubMed

Yoshida, Eriko; Terada, Shin-Ichiro; Tanaka, Yasuyo H; Kobayashi, Kenta; Ohkura, Masamichi; Nakai, Junichi; Matsuzaki, Masanori

2018-05-29

In vivo wide-field imaging of neural activity with a high spatio-temporal resolution is a challenge in modern neuroscience. Although two-photon imaging is very powerful, high-speed imaging of the activity of individual synapses is mostly limited to a field of approximately 200 µm on a side. Wide-field one-photon epifluorescence imaging can reveal neuronal activity over a field of ≥1 mm 2 at a high speed, but is not able to resolve a single synapse. Here, to achieve a high spatio-temporal resolution, we combine an 8 K ultra-high-definition camera with spinning-disk one-photon confocal microscopy. This combination allowed us to image a 1 mm 2 field with a pixel resolution of 0.21 µm at 60 fps. When we imaged motor cortical layer 1 in a behaving head-restrained mouse, calcium transients were detected in presynaptic boutons of thalamocortical axons sparsely labeled with GCaMP6s, although their density was lower than when two-photon imaging was used. The effects of out-of-focus fluorescence changes on calcium transients in individual boutons appeared minimal. Axonal boutons with highly correlated activity were detected over the 1 mm 2 field, and were probably distributed on multiple axonal arbors originating from the same thalamic neuron. This new microscopy with an 8 K ultra-high-definition camera should serve to clarify the activity and plasticity of widely distributed cortical synapses.

The Relationship between a Linear Combination of Intelligence, Musical Background, Rhythm Ability and Tapping Ability to Typewriting Speed and Accuracy.

ERIC Educational Resources Information Center

Fante, Cheryl H.

This study was conducted in an attempt to identify any predictor or combination of predictors of a beginning typewriting student's success. Variables of intelligence, rhythmic ability, musical background, and tapping ability were combined to study their relationship to typewriting speed and accuracy. A sample of 109 high school students was…

Advances in Laser Microprobe (U-Th)/He Geochronology

NASA Astrophysics Data System (ADS)

van Soest, M. C.; Monteleone, B. D.; Boyce, J. W.; Hodges, K. V.

2008-12-01

The development of the laser microprobe (U-Th)/He dating method has the potential to overcome many of the limitations that affect conventional (U-Th)/He geochronology. Conventional single- or multi-crystal (U- Th)/He geochronology requires the use of pristine, inclusion-free, euhedral crystals. Furthermore, the ages that are obtained require corrections for the effects of zoning and alpha ejection based on an ensemble of assumptions before interpretation of their geological relevance is possible. With the utilization of microbeam techniques many of the limitations of conventional (U-Th)/He geochronology can either be eliminated by careful spot selection or accounted for by detailed depth profiling analyses of He, U and Th on the same crystal. Combined He, Th, and U depth profiling on the same crystal potentially even offers the ability to extract thermal histories from the analyzed grains. Boyce et al. (2006) first demonstrated the laser microprobe (U-Th)/He dating technique by successfully dating monazite crystals using UV laser ablation to liberate He and determined U and Th concentrations using a Cameca SX-Ultrachron microprobe. At Arizona State University, further development of the microprobe (U-Th)/He dating technique continues using an ArF Excimer laser connected to a GVI Helix Split Flight Tube noble gas mass spectrometer for He analysis and SIMS techniques for U and Th. The Durango apatite age standard has been successfully dated at 30.7 +/- 1.7 Ma (2SD). Work on dating zircons by laser ablation is currently underway, with initial results from Sri Lanka zircon at 437 +/- 14 Ma (2SD) confirmed by conventional (U-Th)/He analysis and in agreement with the published (U-Th)/He age of 443 +/- 9 Ma (2SD) for zircons from this region in Sri Lanka (Nasdala et al., 2004). The results presented here demonstrate the laser microprobe (U-Th)/He method as a powerful tool that allows application of (U- Th)/He dating to areas of research such as detrital apatite and zircon dating, where conventional (U-Th)/He geochronology has limited applicability. Boyce et al. (2006) GCA 70 (3031-3039), Nasdala et al. (2004) Am. Min. 89 (219-231)

A new design for a green calcium indicator with a smaller size and a reduced number of calcium-binding sites

PubMed Central

Barykina, Natalia V.; Subach, Oksana M.; Doronin, Danila A.; Sotskov, Vladimir P.; Roshchina, Marina A.; Kunitsyna, Tatiana A.; Malyshev, Aleksey Y.; Smirnov, Ivan V.; Azieva, Asya M.; Sokolov, Ilya S.; Piatkevich, Kiryl D.; Burtsev, Mikhail S.; Varizhuk, Anna M.; Pozmogova, Galina E.; Anokhin, Konstantin V.; Subach, Fedor V.; Enikolopov, Grigori N.

2016-01-01

Genetically encoded calcium indicators (GECIs) are mainly represented by two- or one-fluorophore-based sensors. One type of two-fluorophore-based sensor, carrying Opsanus troponin C (TnC) as the Ca2+-binding moiety, has two binding sites for calcium ions, providing a linear response to calcium ions. One-fluorophore-based sensors have four Ca2+-binding sites but are better suited for in vivo experiments. Herein, we describe a novel design for a one-fluorophore-based GECI with two Ca2+-binding sites. The engineered sensor, called NTnC, uses TnC as the Ca2+-binding moiety, inserted in the mNeonGreen fluorescent protein. Monomeric NTnC has higher brightness and pH-stability in vitro compared with the standard GECI GCaMP6s. In addition, NTnC shows an inverted fluorescence response to Ca2+. Using NTnC, we have visualized Ca2+ dynamics during spontaneous activity of neuronal cultures as confirmed by control NTnC and its mutant, in which the affinity to Ca2+ is eliminated. Using whole-cell patch clamp, we have demonstrated that NTnC dynamics in neurons are similar to those of GCaMP6s and allow robust detection of single action potentials. Finally, we have used NTnC to visualize Ca2+ neuronal activity in vivo in the V1 cortical area in awake and freely moving mice using two-photon microscopy or an nVista miniaturized microscope. PMID:27677952

Revisiting the Si Isotope Record of Precambrian Cherts and Banded Iron Formations Using New Experimental Results

NASA Astrophysics Data System (ADS)

Zheng, X. Y.; Satkoski, A.; Beard, B. L.; Reddy, T. R.; Beukes, N. J.; Johnson, C.

2017-12-01

Precambrian Banded iron formations (BIFs) and cherts provide a record of Fe and Si biogeochemical cycling in early Earth marine environments. Much of the focus on BIFs has been the origin and pathways for Fe, but Si is intimately tied to BIF genesis through its connection to Fe minerals, either through direct structural bonding or through sorption. In the Precambrian ocean, aqueous Si contents were high, and it is increasingly recognized that Fe(III)-Si gels were the most likely precursor to BIFs [1]. It is known that Fe-Si bonding affects stable Fe isotope fractionations [2], and our recent experimental work shows this to be true for stable Si isotope fractionations [3, 4]. Silicon isotope fractionations in the Fe-Si system vary from 0‰ to nearly 4‰ in 30Si/28Si ratios with the solid phase being isotopically light depending on Fe:Si ratio [3, 4, and this study], a range far larger than that of 56Fe/54Fe ratios, highlighting the fact that Si isotopes are a highly sensitive tracer of the Fe-Si cycle. This range in Si isotope fractionation factors for the Fe-Si system can explain the full range of δ30Si values measured in Precambrian BIFs, providing a new framework to interpret Precambrian δ30Si records. Our results provide strong support for a model where Fe(III)-Si gels are the precursor phase for BIFs, which in turn affects estimates for the aqueous Fe and Si contents of the Precambrian oceans through changes in Fe-Si gel solubility. Our experiments also showed that microbial dissimilatory iron reduction (DIR) of Fe(III)-Si gel can easily produce a solid with Fe(II)-Fe(III) stoichiometry equal to magnetite, in marked contrast to abiotic incorporation of Fe(II) into Fe(III)-Si gel that resulted in a solid with Fe(II)-Fe(III) stoichiometry much lower than magnetite. Moreover, this DIR process produces a unique, negative δ30Si signature that should be eventually preserved in quartz closely associated with magnetite upon phase transformation of Fe-Si gel, and serve as a bio-signature. This experimental finding well explains the tendency of magnetite-rich BIFs to have lower δ30Si values than hematite-rich BIFs. [1] Konhauser et al., Earth-Science Rev, 2017 [2] Wu et al., GCA, 2012 [3] Zheng et al., GCA, 2016 [4] Reddy et al., GCA, 2016

Flares in Biopsy-Proven Giant Cell Arteritis in Northern Italy

PubMed Central

Restuccia, Giovanna; Boiardi, Luigi; Cavazza, Alberto; Catanoso, Mariagrazia; Macchioni, Pierluigi; Muratore, Francesco; Cimino, Luca; Aldigeri, Raffaella; Crescentini, Filippo; Pipitone, Nicolò; Salvarani, Carlo

2016-01-01

Abstract This study evaluated the frequency, timing, and characteristics of flares in a large cohort of Italian patients with biopsy-proven giant cell arteritis (GCA) and to identify factors at diagnosis able to predict the occurrence of flares. We evaluated 157 patients with biopsy-proven transmural GCA diagnosed and followed at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for whom sufficient information was available from the time of diagnosis until at least 4 years of follow-up. Fifty-seven patients (36.5%) experienced ≥1 flares. Fifty-one (46.4%) of the 110 total flares (88 relapses and 22 recurrences) were experienced during the first 2 years after diagnosis. The majority of relapses occurred with doses of prednisone ≤ 10 mg/day (82.9%), whereas only 3.4% of relapses occurred for doses ≥ 25 mg/day. Polymyalgia rheumatica (46.5%) and cranial symptoms (41.9%) were the most frequent manifestations at the time of the first relapse. Cumulative prednisone dose during the first year and total cumulative prednisone dose were significantly higher in flaring patients compared with those without flares (7.8 ± 2.4 vs 6.7 ± 2.4 g, P = 0.02; 15.5 ± 8.9 vs 10.0 ± 9.2 g, P = 0.0001, respectively). The total duration of prednisone treatment was longer in flaring patients (58 ± 44 vs 30 ± 30 months, P = 0.0001). Patients with disease flares had at diagnosis more frequently systemic manifestations (P = 0.02) and fever ≥ 38°C (P = 0.02), significantly lower hemoglobin levels (P = 0.05), more frequent presence at temporal artery biopsy (TAB) specimens of giant cells (P = 0.04) and intraluminal acute thrombosis (P = 0.007), and more moderate/severe arterial inflammation (P = 0.009) compared with those without flares. In the multivariate model fever ≥ 38 °C (hazard ratio 2.14; 95% confidence interval, 1.06–4.32, P = 0.03) and the severity of inflammatory infiltrate (moderate/severe versus mild) (hazard ratio 5.41; 95% confidence interval, 1.64–17.87, P = 0.006) were significantly associated with an increased risk of flares. In conclusion, a flaring course is common in GCA and it is associated with prolonged GC requirements. Fever at diagnosis and severity of inflammation at TAB appear to predict the development of disease flares. PMID:27175649

Uranium Isotopes in Calcium Carbonate: A Possible Proxy for Paleo-pH and Carbonate Ion Concentration?

NASA Astrophysics Data System (ADS)

Chen, X.; Romaniello, S. J.; Herrmann, A. D.; Wasylenki, L. E.; Anbar, A. D.

2015-12-01

Natural variations of 238U/235U in marine carbonates are being explored as a paleoredox proxy. However, in order for this proxy to be robust, it is important to understand how pH and alkalinity affect the fractionation of 238U/235U during coprecipitation with calcite and aragonite. Recent work suggests that the U/Ca ratio of foraminiferal calcite may vary with seawater [CO32-] concentration due to changes in U speciation[1]. Here we explore analogous isotopic consequences in inorganic laboratory co-precipitation experiments. Uranium coprecipitation experiments with calcite and aragonite were performed at pH 8.5 ± 0.1 and 7.5 ± 0.1 using a constant addition method [2]. Dissolved U in the remaining solution was periodically collected throughout the experiments. Samples were purified with UTEVA resin and 238U/235U was determined using a 233U-236U double-spike and MC-ICP-MS, attaining a precision of ± 0.10 ‰ [3]. Small but resolvable U isotope fractionation was observed in aragonite experiments at pH ~8.5, preferentially enriching heavier U isotopes in the solid phase. 238U/235U of the dissolved U in these experiments can be fit by Rayleigh fractionation curves with fractionation factors of 1.00002 - 1.00009. In contrast, no resolvable U isotope fractionation was detected in an aragonite experiment at pH ~7.5 or in calcite experiments at either pH. Equilibrium isotope fractionation among dissolved U species is the most likely mechanism driving these isotope effects. Our quantitative model of this process assumes that charged U species are preferentially incorporated into CaCO3 relative to the neutral U species Ca2UO2(CO3)3(aq), which we hypothesize to have a lighter equilibrium U isotope composition than the charged U species. According to this model, the magnitude of U isotope fractionation should scale with the fraction of the neutral U species in the solution, in agreement with our experimental results. These findings suggest that U isotope variations in abiotic CaCO3 reflect changes in aqueous U(VI) speciation, which are in turn a function of carbonate ion chemistry and pH. Hence, the door is opened to the development of a possible 238U/235U proxy for the carbonate ion system. [1] DeCarlo et al., (2015), GCA, 162,151-165. [2] Reeder et a., (2001), GCA, 65, 3491-3503. [3] Weyer et al., (2008) GCA 72, 345-359.

The 176Lu-176Hf System as a Tool to Date Meteorites and Trace Early Silicate Differentiation - Requirements and Pitfalls

NASA Astrophysics Data System (ADS)

Bast, R.; Scherer, E. E.; Sprung, P.; Mezger, K.; Bischoff, A.

2016-12-01

The long-lived 176Lu-176Hf system is a potentially precise and robust chronometer, but when applied to meteorites, several "isochrons" exhibit excessive scatter and yield dates up to 300 Myr older than the Solar System [1-3]. Samples from different parent bodies produce similar patterns of scatter, whereas different pieces of the same meteorite yield contradictory results [e.g., 4-5]. These observations are difficult to explain by early Solar System irradiation [6-7] or diffusion [8-11] events. Instead, we infer that terrestrial contamination and weathering are more plausible disturbance mechanisms. Similar effects can, however, also be induced during sample handling [12-13]. Precise and accurate Lu-Hf chronology requires fresh, unaltered samples, and contamination must be removed without disturbing the target minerals. We have investigated various fractions of ALM-A, a trachyandesite from the Almahata Sitta meteorite fall. Impure mineral separates and bulk fractions contain terrestrial contamination as evidenced by excess 176Hf, whereas the purest, handpicked grains and selectively digested phosphate minerals yield a 13-point isochron with an age of 4569 ±24 Ma (MSWD = 1.3) using λ176Lu = 1.867 × 10-11 yr-1 [14-16]. The initial 176Hf/177Hf of 0.279796 ±0.000011 agrees well with other estimates of the initial 176Hf/177Hf of the Solar System [17-18] and supports the assumption of initial isotopic homogeneity among rocky planetary bodies with respect to Hf. [1] Blichert-Toft et al. (2002) EPSL 202, 167-181. [2] Bizzarro et al. (2003) Nature 421, 931-933. [3] Bizzarro et al. (2012) G³ 13, 10.1029/2011GC004003. [4] Bast et al. (under review) GCA. [5] Sanborn et al. (2015) GCA 171, 80-99. [6] Albarède et al. (2006) GCA 70, 1261-1270. [7] Thrane et al. (2010) Astrophys J 717, 861-867. [8] Debaille et al. (2011) LPI Contrib, 1639, 9066. [9] Debaille et al. (2013) Min Mag, 77, 957. [10] Debaille et al. (2014) Meteorit Planet Sci, 49, A5238. [11] Bloch et al. (2016) Goldschmidt, A250. [12] Amelin et al. (2016) Goldschmidt, A57. [13] Scherer & Bast (2016) this meeting. [14] Scherer et al. (2001) Science 293, 683-687. [15] Scherer et al. (2003) Meteorit Planet Sci, 38, A136. [16] Söderlund et al. (2004) EPSL 219, 311-324. [17] Bouvier et al. (2008) EPSL 273, 48-57. [18] Iizuka et al. (2015) PNAS 112, 5331-5336.

Molybdenum isotopes in modern marine hydrothermal Fe/Mn deposits: Implications for Archean and Paleoproterozoic Mo cycles

NASA Astrophysics Data System (ADS)

Goto, K. T.; Hein, J. R.; Shimoda, G.; Aoki, S.; Ishikawa, A.; Suzuki, K.; Gordon, G. W.; Anbar, A. D.

2016-12-01

Molybdenum isotope (δ98/95Mo) variations recorded in Archean and Paleoproterozoic Fe/Mn-rich sediments have been used to constrain ocean redox conditions at the time of deposition (Canfield et al., 2013 PNAS; Planavsky et al., 2014 Nat. Geo.; Kurzweil et al., 2015 GCA). However, except for hydrogenous Fe-Mn crusts (Siebert et al., 2003), δ98/95Mo variation of modern Fe and Mn oxide deposits has been poorly investigated. Marine hydrothermal systems are thought to be the major source of Fe and Mn in Archean and Paleoproterozoic Fe- and Mn-rich sediments. Hence, to accurately interpret Mo isotope data of those ancient sedimentary rocks, it is important to evaluate the possible influence of hydrothermally derived Mo on δ98/95Mo of modern Fe- and Mn-rich sediments. In this study, we analyzed Mo isotopic compositions of one hydrothermal Fe oxide and 15 Mn oxides from five different hydrothermal systems in the modern ocean. The Fe oxide is composed mainly of goethite, and has a δ98/95Mo of 0.7‰, which is 1.4‰ lighter than that of present-day seawater. The observed offset is similar to isotope fractionation observed during adsorption experiments of Mo on goethite (Δ98/95Mogoethite-solution = -1.4 ± 0.5%; Goldberg et al., 2009 GCA). The 15 hydrothermal Mn oxides show large variations in δ98/95Mo ranging from -1.7 to 0.5‰. However, most of the values are similar to those of modern hydrogenous Fe-Mn crusts (Siebert et al., 2003 EPSL), and fall within the range of estimated δ98/95Mo of Mn oxides precipitated from present-day seawater using the isotope offset reported from adsorption experiments (Δ98/95Mo = -2.7 ± 0.3‰; Wasylenki et al., 2008 GCA). These findings indicate that seawater is the dominant source of Mo for modern hydrothermal Fe and Mn deposits. However, the observed large variation indicates that the contribution Mo from local hydrothermal systems is not negligible. The oceanic Mo inventory during the Archean and Paleoproterozoic is thought to be much smaller than that of present-day (Scott et al., 2008 Nature). Hence, δ98/95Mo of Archean and Paleoproterozoic Fe- and Mn-rich sediments could be strongly influenced by hydrothermally derived Mo, which may contrast to modern hydrothermal deposits. Possible Archean and Paleoproterozoic Mo cycles constrained by these data will also be discussed.

Silicon Isotope Geochemistry of Ocean Island Basalts: Search for Deep Mantle Heterogeneities and Evidence for Recycled Altered Oceanic Crust

NASA Astrophysics Data System (ADS)

Pringle, E. A.; Savage, P. S.; Jackson, M. G.; Moreira, M. A.; Day, J. M.; Moynier, F.

2014-12-01

Analyses of Ocean Island Basalts (OIB) have shown that the Earth's mantle contains isotopically distinct components, but debate about the degree and cause of variability persists. The study of silicon (Si) isotopes in OIBs has the potential to elucidate mantle heterogeneities. Relatively large (~several per mil) Si isotopic fractionation occurs in low-temperature environments during precipitation from dissolved Si, where the precipitate is preferentially enriched in the lighter isotopes [1], but only a limited range (~tenths of a per mil) of Si isotope fractionation has been observed due to high-temperature igneous processes [2]. Therefore, Si isotopes may be useful as tracers for the presence of crustal material in OIB source regions in a manner similar to more conventional stable isotope systems, such as oxygen. Here we present the first comprehensive suite of high-precision Si isotopic data obtained by MC-ICP-MS for a diverse set of OIBs representing the EM-1, EM-2, and HIMU mantle components. In general, the Si isotopic compositions of OIBs analyzed here are agreement with previous estimates for Bulk Silicate Earth (BSE). However, small systematic variations are present; the HIMU end-member Mangaia and HIMU-type Cape Verde island São Nicolau are enriched in the light isotopes of Si (δ30Si = -0.37 ± 0.06‰ and δ30Si = -0.39 ± 0.04‰, respectively; errors are 2sd), with compositions intermediary between Mid Ocean Ridge Basalts and chondritic values. Additionally, Iceland samples from volcanic complexes in the Northern Rift Zone show similar Si isotope compositions (on average, δ30Si = -0.40 ± 0.06‰). In contrast, the δ30Si averages of the EM-1 end-member Pitcairn (-0.28 ± 0.07‰), the EM-2 end-member Samoa (-0.31 ± 0.07‰) and other OIB localities do not show any significant difference from previous estimates for the δ30Si value of BSE [3]. The Si isotopic variability in some HIMU-type and Icelandic OIBs most likely reflects the incorporation of recycled altered oceanic crust in the plume source. However, the sampling of a primitive reservoir enriched in the light isotopes of Si, as suggested by [4], cannot be ruled out as a potential source of Si isotope variations in OIBs. References: [1] Ziegler et al., GCA 2005 [2] Savage et al., GCA 2011 [3] Savage et al., EPSL 2010 [4] Huang et al., GCA 2014

Cosmogenic Radionuclides in Antarctic Meteorites: Preliminary Results on Terrestrial Ages and Temporal Phenomena

NASA Astrophysics Data System (ADS)

Michlovich, E.; Vogt, S.; Wolf, S. F.; Elmore, D.; Lipschutz, M. E.

1993-07-01

Since 1969, more than 15,000 meteorites have been recovered from various sites in Antarctica. Differences have been reported between the Antarctic populations and the population of non-Antarctic meteorites in volatile trace- element content, thermoluminescence properties, physical size, and relative distribution of meteorite type [1]. Lipschutz and Samuels [2] developed a method based upon multivariate linear and logistic regression that they applied to interpret trace-element content in Antarctic and non-Antarctic meteorites, showing that the two populations can be chemically distinguished. Since Antarctic meteorites have, on the whole, much longer terrestrial ages than non-Antarctic falls, such differences have been used to support the notion that the flux of meteorites sampled by the Earth has changed in the recent past. A subsequent study [3] showed a statistically significant difference in trace-element content between meteorites from Victoria Land and those found in Queen Maud Land, two groups that seem to have different terrestrial age distributions. Changes in meteorite flux patterns on the order of 60 yr are indicated from a study of Cluster 1 vs. non-Cluster 1 falls [4]. Rapid fluctuations would almost certainly require the existence of co-orbital meteoroid streams, an idea that has been criticized by some [5] on dynamical grounds. To quantify the discussion of a temporal dependence of meteorite flux patterns, and to continue systematic study of Antarctic meteorites, we have measured the contents of the cosmogenic radionuclides ^10Be and ^26Al in the bulk phase, and ^36Cl in the metal phase, of 40 Antarctic specimens that are from the same suite of samples analyzed in the trace-element studies and that were chosen to minimize any chances of paired meteorites. The means and standard deviations of ^10Be and ^26Al activities are 16.4 +/- 3.5 and 48 +/- 8 dpm/kg respectively. Correction for cosmic ray exposure [6,7] and terrestrial ages allows us to estimate the production rates for these radionuclides in this group of meteorites to be 18.2 +/- 2.3 and 58 +/- 13 dpm/kg respectively, consistent with production rates cited for falls [8]. Cosmic ray exposure ages using the ^10Be/^21Ne method outlined by Graf et al. [9] substantially agree with ages calculated from noble gases alone. Similar agreements are obtained between cosmic ray exposure ages based solely on noble gases and those calculated using ^26Al/^21Ne [9]. We calculated terrestrial ages using the secular equilibrium distribution for ^36Cl of 22.8 +/- 3.1 dpm/kg [10]. Our results are similar to those seen by Nishiizumi et al. [10], with a few ages ranging up to several hundred thousand years. It is worth noting that the Yamato meteorites measured in the present study, all of which happen to have been collected in the 1979 recovery effort ("Y79"), have a much older terrestrial age distribution (median age of 140 ka) than the Yamato distribution shown in [10]. We find it interesting that our Yamato age distribution is, however, consistent with the distribution of Y79 ages (median age, 110 ka) listed in [10], and that non-Y79 Yamato meteorites (median age in [10], 22 ka) seem to be responsible for a disproportionate number of the youngest Yamato meteorites. This possible collection area phenomenon is under investigation. Preliminary statistical analysis of the results using the preliminary terrestrial ages calculated here, trace-element data [3,4,11], and the methods elucidated in [2] is consistent with the notion that the meteorite flux sampled by the Earth has changed as a function of time. The latest results will be presented in Vail. References: [1] Koeberl C. and Cassidy W. A. (1991) GCA, 55, 3-18. [2] Lipschutz M. E. and Samuels S. M. (1991) GCA, 55, 19-34. [3] Wolf S. F. and Lipschutz M. E. (1992) LPS XXIII, 1545-1546. [4] Dodd R. T. et al. (1993) JGR, submitted. [5] Wetherill G. W. (1986) Nature, 319, 357-358. [6] Schultz L., personal communication. [7] Schultz L. et al. (1991) GCA, 55, 59-66. [8] Vogt S. et al. (1990) Rev. Geophys., 28, 253-275. [9] Graf Th. et al. (1990) GCA, 54, 2521-2534. [10] Nishiizumi K. et al. (1989) EPSL, 93, 299-313. [11] Lingner D. W. et al. (1987) GCA, 51, 727-739.

Cellular resolution circuit mapping with temporal-focused excitation of soma-targeted channelrhodopsin

PubMed Central

Baker, Christopher A; Elyada, Yishai M; Parra, Andres; Bolton, M McLean

2016-01-01

We describe refinements in optogenetic methods for circuit mapping that enable measurements of functional synaptic connectivity with single-neuron resolution. By expanding a two-photon beam in the imaging plane using the temporal focusing method and restricting channelrhodopsin to the soma and proximal dendrites, we are able to reliably evoke action potentials in individual neurons, verify spike generation with GCaMP6s, and determine the presence or absence of synaptic connections with patch-clamp electrophysiological recording. DOI: http://dx.doi.org/10.7554/eLife.14193.001 PMID:27525487

Complexity in the Chinese stock market and its relationships with monetary policy intensity

NASA Astrophysics Data System (ADS)

Ying, Shangjun; Fan, Ying

2014-01-01

This paper introduces how to formulate the CSI300 evolving stock index using the Paasche compiling technique of weighed indexes after giving the GCA model. It studies dynamics characteristics of the Chinese stock market and its relationships with monetary policy intensity, based on the evolving stock index. It concludes by saying that it is possible to construct a dynamics equation of the Chinese stock market using three variables, and that it is useless to regular market-complexity according to changing intensity of external factors from a chaos point of view.

Exploring the Diversification Discount: A Focus on High-Technology Target Firms

DTIC Science & Technology

2003-03-01

26 3. Breusch - Pagan Test Analysis ……………………………………………………..39 ix AFIT/GCA/ENV/03-01 Abstract When firms choose to acquire...of fit test , the Durbin-Watson test , and the Breusch - Pagan test respectively. A further discussion of the validation of the three regression...addition, the Breusch - Pagan test was employed to objectively test the assumption (Neter, 1996). The test yielded a p-value of 0.990, again

An Airfield Too Far, the Army’s Search for a Runway

DTIC Science & Technology

1990-05-01

just to keep the war going. Pilots flew to the point of e>ý.austion--often nine to ten hours a day witho.t leaving their cockpits. If the British...ground controlled. approach radar (GCA) of post-World War II vintage, However, it does not have a radiation signature as a threat air defense radar. Using...AD-A241 034 zx.R WARL COLLEGE RESEARCH REPORT AN AIRFIELD TOO FAR, THE ARMY’S 5EARCH FOR A RUNWAY DTIC, LIEU.TENANT COLO-NEL KENT V. H~JFFORD, USA

The utility of covariance of combining ability in plant breeding.

PubMed

Arunachalam, V

1976-11-01

The definition of covariances of half- and full sibs, and hence that of variances of general and specific combining ability with regard to a quantitative character, is extended to take into account the respective covariances between a pair of characters. The interpretation of the dispersion and correlation matrices of general and specific combining ability is discussed by considering a set of single, three- and four-way crosses, made using diallel and line × tester mating systems in Pennisetum typhoides. The general implications of the concept of covariance of combining ability in plant breeding are discussed.

The effects of whole body vibration combined biofeedback postural control training on the balance ability and gait ability in stroke patients.

PubMed

Uhm, Yo-Han; Yang, Dae-Jung

2017-11-01

[Purpose] The purpose of this study was to examine the effect of biofeedback postural control training using whole body vibration in acute stroke patients on balance and gait ability. [Subjects and Methods] Thirty stroke patients participated in this study and were divided into a group of 10, a group for biofeedback postural control training combined with a whole body vibration, one for biofeedback postural control training combined with an aero-step, and one for biofeedback postural control training. Biorescue was used to measure the limits of stability, balance ability, and Lukotronic was used to measure step length, gait ability. [Results] In the comparison of balance ability and gait ability between the groups for before and after intervention, Group I showed a significant difference in balance ability and gait ability compared to Groups II and III. [Conclusion] This study showed that biofeedback postural control training using whole body vibration is effective for improving balance ability and gait ability in stroke patients.

Efficiency of circulant diallels via mixed models in the selection of papaya genotypes resistant to foliar fungal diseases.

PubMed

Vivas, M; Silveira, S F; Viana, A P; Amaral, A T; Cardoso, D L; Pereira, M G

2014-07-02

Diallel crossing methods provide information regarding the performance of genitors between themselves and their hybrid combinations. However, with a large number of parents, the number of hybrid combinations that can be obtained and evaluated become limited. One option regarding the number of parents involved is the adoption of circulant diallels. However, information is lacking regarding diallel analysis using mixed models. This study aimed to evaluate the efficacy of the method of linear mixed models to estimate, for variable resistance to foliar fungal diseases, components of general and specific combining ability in a circulant table with different s values. Subsequently, 50 diallels were simulated for each s value, and the correlations and estimates of the combining abilities of the different diallel combinations were analyzed. The circulant diallel method using mixed modeling was effective in the classification of genitors regarding their combining abilities relative to the complete diallels. The numbers of crosses in which each genitor(s) will compose the circulant diallel and the estimated heritability affect the combining ability estimates. With three crosses per parent, it is possible to obtain good concordance (correlation above 0.8) between the combining ability estimates.

Exon sequencing of PKD1 gene in an Iranian patient with autosomal-dominant polycystic kidney disease.

PubMed

Hafizi, Atousa; Khatami, Saeid Reza; Galehdari, Hamid; Shariati, Gholamreza; Saberi, Ali Hossein; Hamid, Mohammad

2014-07-01

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic kidney disorders with the incidence of 1 in 1,000 births. ADPKD is genetically heterogeneous with two genes identified: PKD1 (16p13.3, 46 exons) and PKD2 (4q21, 15 exons). Eighty five percent of the patients with ADPKD have at least one mutation in the PKD1 gene. Genetic studies have demonstrated an important allelic variability among patients, but very few data are known about the genetic variation among Iranian populations. In this study, exon direct sequencing of PKD1 was performed in a seven-year old boy with ADPKD and in his parents. The patient's father was ADPKD who was affected without any kidney dysfunction, and the patient's mother was congenitally missing one kidney. Molecular genetic testing found a mutation in all three members of this family. It was a missense mutation GTG>ATG at position 3057 in exon 25 of PKD1. On the other hand, two novel missense mutations were reported just in the 7-year-old boy: ACA>GCA found in exon 15 at codon 2241 and CAC>AAC found in exon 38 at codon 3710. For checking the pathogenicity of these mutations, exons 15, 25, and 38 of 50 unrelated normal cases were sequenced. our findings suggested that GTG>ATG is a polymorphism with high frequency (60%) as well as ACA>GCA and CAC>AAC are polymorphisms with frequencies of 14% and 22%, respectively in the population of Southwest Iran.

Chloroplast DNA polymorphism and evolutional relationships between Asian cultivated rice (Oryza sativa) and its wild relatives (O. rufipogon).

PubMed

Li, W J; Zhang, B; Huang, G W; Kang, G P; Liang, M Z; Chen, L B

2012-12-17

We analyzed chloroplast DNA (cpDNA) polymorphism and phylogenic relationships between 6 typical indica rice, 4 japonica rice, 8 javanica rice, and 12 Asian common wild rice (Oryza rufipogon) strains collected from different latitudes in China by comparing polymorphism at 9 highly variable regions. One hundred and forty-four polymorphic bases were detected. The O. rufipogon samples had 117 polymorphic bases, showing rich genetic diversity. One hundred and thirty-one bases at 13 sites were identified with indica/japonica characteristics; they showed differences between the indica and japonica subspecies at these sites. The javanica strains and japonica shared similar bases at these 131 polymorphic sites, suggesting that javanica is closely related to japonica. On the basis of length analyses of the open reading frame (ORF)100 and (ORF)29-tRNA-Cys(GCA) (TrnC(GCA)) fragments, the O. rufipogon strains were classified into indica/japonica subgroups, which was consistent with the results of the phylogenic tree assay based on concatenated datasets. These results indicated that differences in indica and japonica also exist in the cpDNA genome of the O. rufipogon strains. However, these differences demonstrated a certain degree of primitiveness and incompleteness, as an O. rufipogon line may show different indica/ japonica attributes at different sites. Consequently, O. rufipogon cannot be simply classified into the indica/japonica types as O. sativa. Our data support the hypothesis that Asian cultivated rice, O. indica and O. japonica, separately evolved from Asian common wild rice (O. rufipogon) strains, which have different indica-japonica differentiation trends.

Mantle Noble Gas Contents Controlled by Serpentinite Subduction

NASA Astrophysics Data System (ADS)

Krantz, J. A.; Parman, S. W.; Kelley, S. P.; Smye, A.; Jackson, C.; Cooper, R. F.

2017-12-01

Noble gases serve as powerful tracers of the mantle's chemical and physical evolution. Analyses of material from subduction zones1, mid-ocean ridge basalts, and ocean island basalts2 indicate that heavy noble gases are being recycled from the surface of the earth into the mantle. The exact mechanism by which these uncharged atoms can be bound to a mineral and the subsequent path of recycling remains unclear, but experimental work suggests that ring structures in silicate minerals are ideal sites for noble gases3. Serpentine contains such ring structures and is abundant in subducting slabs. Developing an understanding of how noble gases are transported sheds light on the large-scale mantle dynamics associated with volatile transport, subduction, convection, and mantle heterogeneity. The solubilities of He, Ne, Ar, Kr, and Xe have been experimentally determined in natural samples of antigorite, the high-pressure polymorph of serpentine. The measured solubilities for all noble gases are high relative to mantle silicates (olivine and pyroxenes)4,5. Mixing lines between the noble gas contents of seawater and serpentinite may explain the noble gas composition of mid-ocean ridge basalts and constrain the source material of EM1, EM2 and HIMU ocean island basalts. 1. Kendrick, M.A. et al., Nature Geoscience, 4, 807-812, 2011 2. Parai, R. and Mukhopadhyay, S., GGG, 16, 719-735, 2015 3. Jackson, C.R.M. et al., GCA, 159, 1-15, 2015 4. Heber, V.S. et al., GCA, 71, 1041-1061, 2007 5. Jackson, C.R.M. et al., EPSL, 384, 178-187, 2013

Comparison of genetically encoded calcium indicators for monitoring action potentials in mammalian brain by two-photon excitation fluorescence microscopy

PubMed Central

Podor, Borbala; Hu, Yi-ling; Ohkura, Masamichi; Nakai, Junichi; Croll, Roger; Fine, Alan

2015-01-01

Abstract. Imaging calcium transients associated with neuronal activity has yielded important insights into neural physiology. Genetically encoded calcium indicators (GECIs) offer conspicuous potential advantages for this purpose, including exquisite targeting. While the catalogue of available GECIs is steadily growing, many newly developed sensors that appear promising in vitro or in model cells appear to be less useful when expressed in mammalian neurons. We have, therefore, evaluated the performance of GECIs from two of the most promising families of sensors, G-CaMPs [Nat. Biotechnol. 19(2), 137–141 (2001)11175727] and GECOs [Science 333(6051), 1888–1891 (2011)21903779], for monitoring action potentials in rat brain. Specifically, we used two-photon excitation fluorescence microscopy to compare calcium transients detected by G-CaMP3; GCaMP6f; G-CaMP7; Green-GECO1.0, 1.1 and 1.2; Blue-GECO; Red-GECO; Rex-GECO0.9; Rex-GECO1; Carmine-GECO; Orange-GECO; and Yellow-GECO1s. After optimizing excitation wavelengths, we monitored fluorescence signals associated with increasing numbers of action potentials evoked by current injection in CA1 pyramidal neurons in rat organotypic hippocampal slices. Some GECIs, particularly Green-GECO1.2, GCaMP6f, and G-CaMP7, were able to detect single action potentials with high reliability. By virtue of greatest sensitivity and fast kinetics, G-CaMP7 may be the best currently available GECI for monitoring calcium transients in mammalian neurons. PMID:26158004

Real-time In Vivo Recording of Arabidopsis Calcium Signals During Insect Feeding Using a Fluorescent Biosensor

PubMed Central

Vincent, Thomas R.; Canham, James; Toyota, Masatsugu; Avramova, Marieta; Mugford, Sam T.; Gilroy, Simon; Miller, Anthony J.; Hogenhout, Saskia; Sanders, Dale

2017-01-01

Calcium ions are predicted to be key signaling entities during biotic interactions, with calcium signaling forming an established part of the plant defense response to microbial elicitors and to wounding caused by chewing insects, eliciting systemic calcium signals in plants. However, the role of calcium in vivo during biotic stress is still unclear. This protocol describes the use of a genetically-encoded calcium sensor to detect calcium signals in plants during feeding by a hemipteran pest. Hemipterans such as aphids pierce a small number of cells with specialized, elongated sucking mouthparts, making them the ideal tool to study calcium dynamics when a plant is faced with a biotic stress, which is distinct from a wounding response. In addition, fluorescent biosensors are revolutionizing the measurement of signaling molecules in vivo in both animals and plants. Expressing a GFP-based calcium biosensor, GCaMP3, in the model plant Arabidopsis thaliana allows for the real-time imaging of plant calcium dynamics during insect feeding, with a high spatial and temporal resolution. A repeatable and robust assay has been developed using the fluorescence microscopy of detached GCaMP3 leaves, allowing for the continuous measurement of cytosolic calcium dynamics before, during, and after insect feeding. This reveals a highly-localized rapid calcium elevation around the aphid feeding site that occurs within a few minutes. The protocol can be adapted to other biotic stresses, such as additional insect species, while the use of Arabidopsis thaliana allows for the rapid generation of mutants to facilitate the molecular analysis of the phenomenon. PMID:28829425

Predictive value of the Movement Assessment Battery for Children - Second Edition at 4 years, for motor impairment at 8 years in children born preterm.

PubMed

Griffiths, Alison; Morgan, Prue; Anderson, Peter J; Doyle, Lex W; Lee, Katherine J; Spittle, Alicia J

2017-05-01

To assess the predictive validity at 4 years of the Movement Assessment Battery for Children - Second Edition (MABC-2) for motor impairment at 8 years in children born preterm. We also aimed to determine if sex, cognition, medical, or social risks were associated with motor impairment at 8 years or with a change in MABC-2 score between 4 years and 8 years. Ninety-six children born at less than 30 weeks' gestation were assessed with the MABC-2 at 4 years and 8 years of age. Motor impairment was defined as less than or equal to the 5th centile. The Differential Ability Scales - Second Edition (DAS-II) was used to measure General Conceptual Ability (GCA) at 4 years, with a score <90 defined as 'below average'. There was a strong association between the MABC-2 total standard scores at 4 years and 8 years (59% variance explained, regression coefficient=0.80, 95% confidence interval [CI] 0.69-0.91, p<0.001). The MABC-2 at 4 years had high sensitivity (79%) and specificity (93%) for predicting motor impairment at 8 years. Below average cognition and higher medical risk were associated with increased odds of motor impairment at 8 years (odds ratio [OR]=15.3, 95% CI 4.19-55.8, p<0.001, and OR=3.77, 95% CI 1.28-11.1, p=0.016 respectively). Sex and social risk did not appear to be associated with motor impairment at 8 years. There was little evidence that any variables were related to change in MABC-2 score between 4 years and 8 years. The MABC-2 at 4 years is predictive of motor functioning in middle childhood. Below average cognition and higher medical risk may be predictors of motor impairment. © 2017 Mac Keith Press.

ATF4, A Novel Mediator of the Anabolic Actions of PTH on Bone

DTIC Science & Technology

2012-01-01

5-CTG CAA ATG GCA GCC CTG GTG AC-3 (reverse). For all primers the amplification was performed as follows: initial denaturation at 95 C for 10 min...rat Atf4, 5-ATG GCT TGG CCA GTG CCTCAGA-3 (forward), 5-GCTCTGGAGTGGAAGACA GAA C-3 (reverse); mouse/ratHprt, 5-GTT GAG AGA TCA TCT CCA CC-3...primers used for real-time PCR were: cyclin D1 (GenBank Accession number-NM-007631), 50 GAG GAG GGG GAA GTG GAG GA 30 (forward, þ1,049-bp), 50 CCT CTT TGC

U-Th-Pb and Sm-Nd Isotopic Systematics of the Goalpara Ureilite

NASA Astrophysics Data System (ADS)

Torigoye, N.; Misawa, K.; Tatsumoto, M.

1993-07-01

One of the interesting features of ureilites is the light REE-enriched component that is dissolved by HNO3 leaching [1,2]. In this work, we performed acid-leaching of several mineral fractions from Goalpara ureilite for U-Th-Pb and Sm-Nd analyses. Olivine and pyroxene grains were hand-picked from 150-300- micrometer-sized fraction. Because they still contained carbon and metal sulfide they were further crushed to <63 micrometers and metal was removed with a hand magnet. These separates and whole-rock powders were washed by ethanol, and leached in 0.01N HBr, 1N HNO3, and in some cases, 7N HNO3. Concentrations of U, Th, and Pb in residues are 0.05-0.3 ppb, 0.1-0.7 ppb, and 5-100 ppb, respectively, corresponding to <=0.01X CI chondrites. Lead isotopic compositions of the residues are less radiogenic and close to Canon Diablo troilite (CDT) Pb [3] (Fig. 1). The U-Pb and Th-Pb ages of all the fractions are older than 4.5 Ga, indicating terrestrial Pb contamination (MT). Because of low concentration of U, Th, and Pb, a small amount of Pb can have a significant effect on the U-Pb and Th-Pb model ages. 238U/204Pb (mu) value of the least contaminated residue is 3, which is higher than mu (0.14-0.5) value of carbonaceous chondrites [3,4]. The higher mu value may be due to either volatile depletion by nebula fractionation or to depletion of Pb during segregation of sulfide that occurred prior to the formation of ureilite as an ultramafic cumulate. The Sm and Nd abundances in the residues are also extremely low; 0.4-2 ppb and 1-2.5 ppb, respectively, corresponding to 0.002-0.01X CI chondritic abundances. All the residues show high 147Sm/144Nd ratios (0.23 ~ 0.44), and the fraction with the highest Sm/Nd plots on the 4.55 Ga chondritic isochron (Fig. 2). The 1N HNO3 leachates do not contain light-REE-enriched components, except for the samples containing black metal-carbon phases, which also contain a large amount of terrestrial Pb in the residual fractions. Therefore, interstitial carbon-metal phases may have adsorbed terrestrial contamination of the incompatible elements, which are significantly depleted in the ureilites. References: [1] Boynton W. V. et al. (1976) GCA ,40, 1439-1447. [2] Goodrich C. A. et al. (1991) GCA, 55, 829-848. [3] M. Tatsumoto et al. (1973) Science, 180, 1278-1283. [4] Tatsumoto M. et al. (1976) GCA, 40, 617-634.

What's Hot and What's Not: Multivariate Statistical Analysis of Ten Labile Trace Elements in H-Chondrite Population Pairs

NASA Astrophysics Data System (ADS)

Wolf, S. F.; Lipschutz, M. E.

1993-07-01

Dodd et al. [1] found that, from their circumstances of fall, 17 H chondrites ("H Cluster 1") which fell in May, from 1855 to 1895, are distinguishable from other H chondrite falls and apparently derive from a co-orbital stream of meteoroids. From data for 10 moderately to highly labile trace elements (Rb, Ag, Se, Cs, Te, Zn, Cd, Bi, Tl, In), they used two multivariate statistical techniques--linear discriminant analysis and logistic regression--to demonstrate that 1. 13 H Cluster 1 chondrites are compositionally distinguishable from 45 other H chondrite falls, probably because of differences in thermal histories of the meteorites' parent materials; 2. The reality of the compositional differences between the populations of falls are beyond any reasonable statistical doubt. 3. The compositional differences are inconsistent with the notion that the results reflect analytical bias. We have used these techniques to assess analogous data for various H chondrite populations [2-4] with results that are listed in Table 1. These data indicate that 1. There is no statistical reason to believe that random populations from Victoria Land, Antarctica, differ compositionally from each other. 2. There is significant statistical reason to believe that the H chondrite population recovered from Victoria Land, Antarctica, differs compositionally from that from Queen Maud Land, Antarctica, and from falls. 3. There is no reason to believe that the H chondrite population recovered from Queen Maud Land, Antarctica, differs compositionally from falls. 4. These observations can be made either by data obtained by one analyst or several. These results, coupled with earlier ones [5], demonstrate that trivial explanations cannot explain compositional differences involving labile trace elements in pairs of H chondrite populations. These differences must then reflect differences of preterrestrial thermal histories of the meteorites' parent materials. Acceptance of these differences as preterrestrial has led to predictions subsequently verified by others (meteoroid and asteroid stream discoveries, differencesin thermoluminescence or TL). We predict that a TL difference will be seen between the populations of falls defined by Dodd et al. [1]. References: [1] Dodd R. T. et al. (1993) JGR, submitted. [2] Lingner D. W. et al. (1987) GCA, 51, 727-739. [3] Dennison J. E. and Lipschutz M. E. (1987) GCA, 51, 741-754. [4] Wolf S. F. and Lipschutz M. E. (1993) in Advances in Analytical Geochemistry (M. Hyman and M. Rowe, eds.), in press. [5] Wang M.-S. et al. (1992) Meteoritics, 27, 303. [6] Lipschutz M. E. and Samuels S. M. (1991) GCA, 55, 19-47. Table 1, which appears in the hard copy, shows a multivariate statistical analysis of H chondrite population pairs using 10 labile trace elements (number of meteorites in population in parentheses).

The Systematics of Light Lithophile Elements (Li, Be, B) in Lunar Picritic Glasses

NASA Astrophysics Data System (ADS)

Shearer, C. K.; Layne, G. D.; Papike, J. J.

1993-07-01

Lunar picritic glasses are thought to be the product of either partial melting of the deep lunar mantle followed by rapid ascent [1,2] or polybaric partial melting initiated in the deep lunar mantle [3]. The near primary compositions of these volcanic glasses provide us with a unique perspective for evaluating mare basaltic magmatism and the characteristics and evolution of the lunar mantle. Because of their obvious importance in deciphering the evolution of the Earth-Moon system, we have initiated an extensive trace element study of these picritic glasses using ion microprobe techniques. Here, we report the initial results of light lithophile element (LLE) analyses of these glasses. This is the first reported study of LLE in lunar basalts. The LLE have only recently received attention in terrestrial basaltic systems [4-6]. Their correlations with other more routinely analyzed trace elements (Li:Yb or V, Be:Nd, B:K) in a variety of terrestrial mantle environments have yielded several important insights into mantle magmatism [4-6]. Ion microprobe analyses of the glasses were conducted using a Cameca 4f ion microprobe operated on the UNM campus. The light lithophile elements were analyzed under the following conditions: 10-kV O- primary beam, 8-nA primary beam current, 10-15-micrometer beam diameter, sample voltage offset of -70 +- 25 V, and a 150-micrometer secondary ion image field with a 33-micrometer field aperature inserted. Counting times included background (2 seconds), 30Si (2 seconds), 7Li (2 seconds), 9Be (4 seconds), and 11B (8 seconds). Each analysis involved 30 to 40 counting cycles. These counting times resulted in precision for Li of better than 1.2% and for B and Be of better than 2.2%. Standards for Li, Be, and B in basaltic glass matrices were kindly provided by J. Ryan [4-6]. Calibration curves (LLE/30Si x wt% SiO2 vs. LLE concentration) were originally defined by a minimum of five standards for each element and are linear for the concentration ranges found in the picritic lunar glasses. Picritic glasses analyzed in the initial study were from the Apollo 12, 14, 15, and 17 sites. This suite of glasses ranged in TiO2 from 0.3 to 17 wt%. All glasses had been previously analyzed for major and trace elements (REE, Cr, V, Sr, Ba, Co, Zr) by electron microprobe and ion microprobe [2]. The LLE show a wide range of variability with Li ranging from 1.2 to 23.8 ppm, Be ranging from 0.06 to 3.09 ppm, and B ranging from 0.20 to 3.87 ppm. Traverses across individual glass beads suggest they are homogeneous with regard to LLE. Except for the A17 VLT glasses and the A15 yellow glasses, the individual glass groups [1] show very limited LLE variability. LLE content is positively correlated to TiO2 content. LLE concentrations also parallel the enrichment of other lithophile elements such as Ba, Zr, Sr, and the REE. Unlike terrestrial basalts [4-6], the concentration of LLE in the picritic glasses is negatively correlated with SiO2 and MgO. B/Be ranges from 0.40 to 4.6. Over 85% of the analyzed glasses have B/Be between 0.9 and 3.0, similar to the average B/Be value of 3 for MORB [6]. Li/B and Li/Be values range from 3.2 to 30.8 and 2.7 to 41.7, respectively. These LLE ratios are not correlated with TiO2, but appear to be characteristic of individual sampling sites and therefore reflect subtle differences in the sources of the picritic magmas. The LLE and LLE ratios also indicate a KREEP component had been incorporated into some of these picritic magmas. Shearer and Papike [2] suggested this incorporation occurs in the zone of melting and reflected overturning of the LMO cumulate pile. The initial data reported here suggest that the LLE may be useful in deciphering the mare basalt record. Further analyses of these glasses will allow a more detailed comparison of picritic glass sources with mare basalt sources and a better interpretation of the compositional relationships among picritic glasses. Acknowledgments: SIMS analyses were performed at the UNM/SNL Ion Microprobe Facility, a joint operation of the Institute of Meteoritics, UNM, and Sandia National Laboratories. This research was funded by NASA grant NAGW-3347. References: [1] Delano J. W. (1986) Proc. LPSC, 16th, in JGR, XX D201-D213. [2] Shearer C. K. and Papike J. J. (1993) GCA, in review. [3] Longhi J. (1992) GCA, 56, 2235-2252. [4] Ryan J. G. and Langmuir C. H. (1987) GCA, 51, 1727- 1741. [5] Ryan J. G. and Langmuir C. H. (1988) GCA, 52, 237-244. [6] Ryan J. G. and Langmuir C. H. (1993) GCA, 57, 1489-1498.

Primordial Terrestrial Xe from the Viewpoint of CFF-Xe

NASA Astrophysics Data System (ADS)

Meshik, A. P.; Shukolyukov, Yu. A.; Jessberger, E. K.

1995-09-01

We have already reported [7, 23] on the non-linear isotope mass-fractionation of fission Xe by migration of the precursors I, Te, Sn, and Sb and simultaneous fission of heavy nuclei. Xe with anomalous isotopic pattern was found in a number of meteorites and terrestrial materials and was named CFF-Xe (Chemically Fractionated Fission Xe). It is characterized by an up eightfold ^132Xe and ^131Xe excesses coupled with smaller ^134Xe and ^129Xe excesses. The present work is aimed to estimate the role of CFF-Xe in the terrestrial lithosphere and specifically deals with the problem of the isotopic composition of primordial terrestrial Xe. Due to variations of the migration conditions the isotopic structure of CFF-Xe is not well established and is even not reproducible in the same rock [2]. Nevertheless, we have tried to estimate the composition of CFF-Xe by investigating all available isotopic data of Xe of presumable mantle origin. This is Xe in MORB [29, 1, 12] and ocean island glasses [1, 28], in diamonds [17], in volcanic rocks [29, 8, 9, 21], in volcanic glasses from pillow basalts [16, 6], continental igneous rocks [1, 24, 10, 22], carbonatites and granitoids [1] as well as Xe in natural gases [3, 24, 11, 4, 15]. All data are plotted Fig. 1 where we also suggest end members of the observed scattering. Optimized slopes of CFF-lines are shown as well as the position of the initial points which we regard as primordial terrestrial Xe (Xe0). The isotopic composition of CFF-Xe and Xe0 are given in Tab. 1. The abundances of ^124Xe and ^126Xe in mantle derived samples are very uncertain, but since ^128Xe/^130Xe in Xea and Xe0 is very similar we propose the same ^124Xe/^130Xe and ^126Xe/^130Xe ratios for both Xea and Xe0. If so, AVCC-Xe is simply Xe0 with an admixture of L-Xe, and atmospheric xenon Xea consists of Xe0, CFF-Xe and a small amount of fission Xe (92.5%Xe0 + 5.3%CFF-Xe + 2.2%XeF). Thus, a number of old problems in xenology are removed. The hypothetic components U-Xe or atmosphere-like Xe are not required anymore. Instead, experimentally identified Xe0 can be regarded as primordial terrestrial Xe with an isotopic composition close to AVCC-Xe. Isotopic mass-fractionation is not needed to be involved. Concerning ^129Xe in the mantle, it seems to be part of CFF-Xe rather than the product of primordial 129I decay. This interpretation is supported by the observation of 129I excesses near uranium deposits that provides an additional argument in favor the CFF-Xe hypothesis [5, 14]. This work is supported by INTAS # 94-2397. References: [1] Allegre C. J. et al. (1983) Nature, 303, 762-766. [2] Azuma Sh. et al. (1993) EPSL, 114, 341-352. [3] Boulos M. S. et al. (1971) Science, 174, 1334-1336. [4] Caffee M. W. et al. (1988) AGU Meeting in San Francisco, reprint. [5] Fabrika-Martin J. et al. (1989) GCA, 53, 1817-1823.[6] Hiyagon H. et al. (1992) GCA, 56, 1301-1316. [7] Jessberger E. K. et al. (1992) LPS XXIII, 615-616. [8] Kaneoka I. et al. (1978) EPSL, 39, 382-386. [9] Kaneoka I. et al. (1983) EPSL, 66, 427-437. [10] Levsky L. K. (1993) personal communication. [11] Lin W. J. and Manuel O. K. (1987) Geochem. J., 2, 197-207. [12] Marty B. (1989) EPSL, 94, 45-56. [13] Meshik A. P. (1988) Ph.D. thesis , Vernadsky Institute, Moscow, 211 pp., in Russian. [14] Michelot J. L. et al. (1989) GCA, 53, 1803-1815. [15] Murty S. V. S. (1992) Chem. Geol., 94, 229-240. [16] Ozima M. and Podosek F. A. (1983) Noble Gas Geochemistry, Cambridge Univ., 367 pp. [17] Ozima M. and Zashu S. (1991) EPSL, 105, 13-27. [18] Ozima M. et al. (1983) EPSL, 62, 24-40. [19] Pepin R. O. (1993) preprint. [20] Phinney D. et al. (1978) JGR, 83, 2313-2319. [21] Poreda J. and Farley K. A. (1992) EPSL, 113, 129-144. [22] Schafer K. et al. (1993) Jahresbericht, 244-245, MPI fur Kernphysik, Heidelberg. [23] Shukolyukov Yu. A. et al. (1994) GCA, 58, 3075-3092. [24] Smith S. P. (1984) GCA, 48, 1033-1041. [25] Smith S. P.and Reinolds J. H. (1981) EPSL, 54, 236-238. [26] Staudacher Th. (1987) Nature, 325, 605-609. [27] Staudacher Th. and Allegre C. J. (1982) EPSL, 60, 389-406. [28] Staudacher Th. et al. (1986) Chem. Geol., 56, 193-205. [29] Thompson D. P. (1978) Phys. Earth Planet. Inter., 17, 98-107.

Altered effective connectivity anchored in the posterior cingulate cortex and the medial prefrontal cortex in cognitively intact elderly APOE ε4 carriers: a preliminary study.

PubMed

Luo, Xiao; Li, Kaicheng; Jia, Y L; Zeng, Qingze; Jiaerken, Yeerfan; Qiu, Tiantian; Huang, Peiyu; Xu, Xiaojun; Shen, Zhujing; Guan, Xiaojun; Zhou, Jiong; Wang, Chao; Xu, J J; Zhang, Minming

2018-03-17

The APOE ε4 allele is associated with impaired intrinsic functional connectivity in neural networks, especially in the default mode network (DMN). However, effective connectivity (EC) reflects the direct causal effects of one brain region to another, which has rarely been investigated. Recently, Granger causality analysis (GCA) proved suitable for the study of directionality in neuronal interactions. Using GCA, we examined the differences in the EC between the anterior medial prefrontal cortex/posterior cingulate cortex (aMPFC/PCC) and the whole brain in 17 ε4 carrying and 32 non-carrying cognitively intact elderly individuals. Furthermore, correlation analyses were performed between the abnormal EC and cognition/neuropathological indices. Compared with the non-carriers, the results showed that the ε4 carriers exhibited decreased EC from the PCC to the whole brain in the middle temporal gyrus (MTG), the anterior cingulate cortex (ACC), and the precuneus (PCu). Meanwhile, the ε4 carriers demonstrated increased EC from the whole brain to the aMPFC in the inferior parietal lobe (IPL) and the postcentral gyrus (PCG). The correlation analyses suggested that the EC from the IPL/PCG to the aMPFC was related to episodic memory in non-carriers, while the decreased EC from the PCC to the ACC was associated with increased levels of t-tau in the ε4 carriers. In ε4 carriers, a negative influence can be traced from the PCC to both the anterior and posterior DMN subsystems; meanwhile, the anterior DMN subsystem receives compensatory effects from the parietal cortex. Early increases in AD-related pathologies in the PCC may act as first factors during this pathological process.

Calibration of the clumped isotope thermometer for planktic foraminifers

NASA Astrophysics Data System (ADS)

Meinicke, N.; Ho, S. L.; Nürnberg, D.; Tripati, A. K.; Jansen, E.; Dokken, T.; Schiebel, R.; Meckler, A. N.

2017-12-01

Many proxies for past ocean temperature suffer from secondary influences or require species-specific calibrations that might not be applicable on longer time scales. Being thermodynamically based and thus independent of seawater composition, clumped isotopes in carbonates (Δ47) have the potential to circumvent such issues affecting other proxies and provide reliable temperature reconstructions far back in time and in unknown settings. Although foraminifers are commonly used for paleoclimate reconstructions, their use for clumped isotope thermometry has been hindered so far by large sample-size requirements. Existing calibration studies suggest that data from a variety of foraminifer species agree with synthetic carbonate calibrations (Tripati, et al., GCA, 2010; Grauel, et al., GCA, 2013). However, these studies did not include a sufficient number of samples to fully assess the existence of species-specific effects, and data coverage was especially sparse in the low temperature range (<10 °C). To expand the calibration database of clumped isotopes in planktic foraminifers, especially for colder temperatures (<10°C), we present new Δ47 data analysed on 14 species of planktic foraminifers from 13 sites, covering a temperature range of 1-29 °C. Our method allows for analysis of smaller sample sizes (3-5 mg), hence also the measurement of multiple species from the same samples. We analyzed surface-dwelling ( 0-50 m) species and deep-dwelling (habitat depth up to several hundred meters) planktic foraminifers from the same sites to evaluate species-specific effects and to assess the feasibility of temperature reconstructions for different water depths. We also assess the effects of different techniques in estimating foraminifer calcification temperature on the calibration. Finally, we compare our calibration to existing clumped isotope calibrations. Our results confirm previous findings that indicate no species-specific effects on the Δ47-temperature relationship measured in planktic foraminifers.

A framework for the use of single-chemical transcriptomics data in predicting the hazards associated with complex mixtures of polycyclic aromatic hydrocarbons.

PubMed

Labib, Sarah; Williams, Andrew; Kuo, Byron; Yauk, Carole L; White, Paul A; Halappanavar, Sabina

2017-07-01

The assumption of additivity applied in the risk assessment of environmental mixtures containing carcinogenic polycyclic aromatic hydrocarbons (PAHs) was investigated using transcriptomics. MutaTMMouse were gavaged for 28 days with three doses of eight individual PAHs, two defined mixtures of PAHs, or coal tar, an environmentally ubiquitous complex mixture of PAHs. Microarrays were used to identify differentially expressed genes (DEGs) in lung tissue collected 3 days post-exposure. Cancer-related pathways perturbed by the individual or mixtures of PAHs were identified, and dose-response modeling of the DEGs was conducted to calculate gene/pathway benchmark doses (BMDs). Individual PAH-induced pathway perturbations (the median gene expression changes for all genes in a pathway relative to controls) and pathway BMDs were applied to models of additivity [i.e., concentration addition (CA), generalized concentration addition (GCA), and independent action (IA)] to generate predicted pathway-specific dose-response curves for each PAH mixture. The predicted and observed pathway dose-response curves were compared to assess the sensitivity of different additivity models. Transcriptomics-based additivity calculation showed that IA accurately predicted the pathway perturbations induced by all mixtures of PAHs. CA did not support the additivity assumption for the defined mixtures; however, GCA improved the CA predictions. Moreover, pathway BMDs derived for coal tar were comparable to BMDs derived from previously published coal tar-induced mouse lung tumor incidence data. These results suggest that in the absence of tumor incidence data, individual chemical-induced transcriptomics changes associated with cancer can be used to investigate the assumption of additivity and to predict the carcinogenic potential of a mixture.

Genetic dissection of the pre-eclampsia susceptibility locus on chromosome 2q22 reveals shared novel risk factors for cardiovascular disease

PubMed Central

Johnson, Matthew P.; Brennecke, Shaun P.; East, Christine E.; Dyer, Thomas D.; Roten, Linda T.; Proffitt, J. Michael; Melton, Phillip E.; Fenstad, Mona H.; Aalto-Viljakainen, Tia; Mäkikallio, Kaarin; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Laivuori, Hannele; Austgulen, Rigmor; Blangero, John; Moses, Eric K.; Pouta, Anneli; Kivinen, Katja; Ekholm, Eeva; Hietala, Reija; Sainio, Susanna; Saisto, Terhi; Uotila, Jukka; Klemetti, Miira; Inkeri Lokki, Anna; Georgiadis, Leena; Huovari, Elina; Kortelainen, Eija; Leminen, Satu; Lähdesmäki, Aija; Mehtälä, Susanna; Salmen, Christina

2013-01-01

Pre-eclampsia is an idiopathic pregnancy disorder promoting morbidity and mortality to both mother and child. Delivery of the fetus is the only means to resolve severe symptoms. Women with pre-eclamptic pregnancies demonstrate increased risk for later life cardiovascular disease (CVD) and good evidence suggests these two syndromes share several risk factors and pathophysiological mechanisms. To elucidate the genetic architecture of pre-eclampsia we have dissected our chromosome 2q22 susceptibility locus in an extended Australian and New Zealand familial cohort. Positional candidate genes were prioritized for exon-centric sequencing using bioinformatics, SNPing, transcriptional profiling and QTL-walking. In total, we interrogated 1598 variants from 52 genes. Four independent SNP associations satisfied our gene-centric multiple testing correction criteria: a missense LCT SNP (rs2322659, P = 0.0027), a synonymous LRP1B SNP (rs35821928, P = 0.0001), an UTR-3 RND3 SNP (rs115015150, P = 0.0024) and a missense GCA SNP (rs17783344, P = 0.0020). We replicated the LCT SNP association (P = 0.02) and observed a borderline association for the GCA SNP (P = 0.07) in an independent Australian case–control population. The LRP1B and RND3 SNP associations were not replicated in this same Australian singleton cohort. Moreover, these four SNP associations could not be replicated in two additional case–control populations from Norway and Finland. These four SNPs, however, exhibit pleiotropic effects with several quantitative CVD-related traits. Our results underscore the genetic complexity of pre-eclampsia and present novel empirical evidence of possible shared genetic mechanisms underlying both pre-eclampsia and other CVD-related risk factors. PMID:23420841

Solitary Fibrous Tumors of the Head and Neck: A Multi-Institutional Clinicopathologic Study.

PubMed

Smith, Steven C; Gooding, William E; Elkins, Matthew; Patel, Rajiv M; Harms, Paul W; McDaniel, Andrew S; Palanisamy, Nallasivam; Uram-Tuculescu, Cora; Balzer, Bonnie B; Lucas, David R; Seethala, Raja R; McHugh, Jonathan B

2017-12-01

Solitary fibrous tumors (SFTs) of the head and neck are uncommon. Lesions previously diagnosed in the head and neck as hemangiopericytomas (HPCs), giant cell angiofibromas (GCAs), and orbital fibrous histiocytomas (OFHs) are now recognized as within the expanded spectrum of SFTs. To better understand the clinicopathologic profile of head and neck SFTs, we performed a multi-institutional study of 88 examples. There was no sex predilection (F:M ratio 1.2), and the median patient age was 52 years (range: 15 to above 89 y). The sinonasal tract and orbit were the most common sites involved (30% and 25%), followed by the oral cavity and salivary glands (15% and 14%). Original diagnoses included HPC (25%), SFT (67%), and OFH (6%), with 1 SFT and 1 OFH noted as showing GCA-like morphology. On review, the predominant histologic pattern was classic SFT-like in 53% and cellular (former HPC-like) in 47%; lipomatous differentiation (8%) and GCA-like pattern (7%) were less prevalent. Subsets demonstrated nuclear atypia (23%), epithelioid morphology (15%), or coagulative necrosis (6%). Infiltrative growth (49%) and osseous invasion (82%) were prevalent among evaluable cases. Of the 48 SFTs with follow-up (median: 43 mo), 19 showed recurrence (40%). Of these, 4 patients were alive with disease and 4 dead of disease. Size and mitotic rate were negative prognosticators using a joint prognostic proportional hazards regression model. Three patients experienced metastasis, to lungs, parotid, bone, and skull base, including one case showing overtly sarcomatous "dedifferentiation." As a group, SFTs present in a wide anatomic and morphologic spectrum in the head and neck. Only rare examples metastasize or cause death from disease. However, the fairly high local recurrence rate underscores their aggressive potential and highlights the importance of prospective recognition.

Detection of endogenous DNA adducts, O-carboxymethyl-2'-deoxyguanosine and 3-ethanesulfonic acid-2'-deoxycytidine, in the rat stomach after duodenal reflux.

PubMed

Terasaki, Masaru; Totsuka, Yukari; Nishimura, Koichi; Mukaisho, Ken-Ichi; Chen, Kuan-Hao; Hattori, Takanori; Takamura-Enya, Takeji; Sugimura, Takashi; Wakabayashi, Keiji

2008-09-01

The endogenous DNA adducts O(6)-carboxymethyl-deoxyguanosine (O(6)-CM-dG) and 3-ethanesulfonic acid-deoxycytidine (3-ESA-dC) are produced from N-nitroso bile acid conjugates, such as N-nitrosoglycocholic acid (NO-GCA) and N-nitrosotaurocholic acid (NO-TCA), respectively. Formation of these DNA adducts in vivo was here analyzed by 32P-postlabeling in the glandular stomach of rats subjected to duodenal content reflux surgery. In this model, all duodenal contents, including bile acid conjugates, flow back from the jejunum into the gastric corpus. The levels of O(6)-CM-dG found at 4 and 8 weeks after surgery were 40.9 +/- 9.4 and 56.3 +/- 3.2 per 10(8) nucleotides, respectively, whereas the sham operation groups had values of 5.8 +/- 2.3 and 5.9 +/- 0.5 per 10(8) nucleotides. Moreover, adduct spots corresponding to 3-ESA-dC were detected in both duodenal reflux and sham operation groups and levels in the duodenal reflux groups were around four-fold elevated at 11.2 +/- 1.0 and 8.9 +/- 1.0 per 10(8) nucleotides after 4 and 8 weeks, respectively. When the duodenal reflux animals were treated with a nitrite trapping agent, thiazolidine- 4-carboxylic acid (thioproline, TPRO), the levels of O(6)-CM-dG and 3-ESA-dC were reduced to the same levels as in the sham operation animals. These observations suggest that NO-TCA and NO-GCA are formed by nitrosation of glycocholic acid and taurocholic acid, respectively, and these nitroso compounds produce DNA adducts in the glandular stomach of rats subjected to duodenal content reflux surgery.

The Complete Chloroplast Genome of Ginkgo biloba Reveals the Mechanism of Inverted Repeat Contraction

PubMed Central

Wu, Chung-Shien; Huang, Ya-Yi; Chaw, Shu-Miaw

2012-01-01

We determined the complete chloroplast genome (cpDNA) of Ginkgo biloba (common name: ginkgo), the only relict of ginkgophytes from the Triassic Period. The cpDNA molecule of ginkgo is quadripartite and circular, with a length of 156,945 bp, which is 6,458 bp shorter than that of Cycas taitungensis. In ginkgo cpDNA, rpl23 becomes pseudo, only one copy of ycf2 is retained, and there are at least five editing sites. We propose that the retained ycf2 is a duplicate of the ancestral ycf2, and the ancestral one has been lost from the inverted repeat A (IRA). This loss event should have occurred and led to the contraction of IRs after ginkgos diverged from other gymnosperms. A novel cluster of three transfer RNA (tRNA) genes, trnY-AUA, trnC-ACA, and trnSeC-UCA, was predicted to be located between trnC-GCA and rpoB of the large single-copy region. Our phylogenetic analysis strongly suggests that the three predicted tRNA genes are duplicates of trnC-GCA. Interestingly, in ginkgo cpDNA, the loss of one ycf2 copy does not significantly elevate the synonymous rate (Ks) of the retained copy, which disagrees with the view of Perry and Wolfe (2002) that one of the two-copy genes is subjected to elevated Ks when its counterpart has been lost. We hypothesize that the loss of one ycf2 is likely recent, and therefore, the acquired Ks of the retained copy is low. Our data reveal that ginkgo possesses several unique features that contribute to our understanding of the cpDNA evolution in seed plants. PMID:22403032

Etiology and Prevention of Esophageal Cancer

PubMed Central

Yang, Chung S.; Chen, Xiaoxin; Tu, Shuiping

2016-01-01

Background Esophageal cancer (EC) occurs commonly, especially in Asia, and is the sixth leading cause of cancer deaths worldwide. Recently, great progress has been made in research on the etiology and prevention of EC. Summary The major risk factors for esophageal squamous cell carcinoma (ESCC) are tobacco smoking and alcohol drinking, which act synergistically. Dietary parameters, including dietary carcinogens and insufficiency of micronutrients, could also be important risk factors in certain areas. A common etiological factor for both EC and some other cancers are low levels of intake of fruits and vegetables. With improvements in diet and drinking water in developing countries, the incidence of ESCC decreased. However, in economically well-developed countries, the incidence of esophageal adenocarcinoma (EAC) has markedly increased in the past 40 years. The major etiological factor for EAC is gastroesophageal reflux, which is also an etiological factor for gastric cardia adenocarcinoma (GCA). In certain areas of China, the occurrence of GCA is closely related to ESCC. Susceptibility genes for EC are starting to be discovered, and this may help to identify high-risk groups that have more need for preventive measures. Mitigation of the risk factors, early detection and treatment of precancerous lesions are effective approaches for prevention. Smoking cessation, avoidance of excessive alcohol, meat and caloric consumption, increasing physical activity and frequent consumption of vegetables and fruits are prudent lifestyle modifications for the prevention of EC as well as other diseases. Key Message The etiology of EC includes tobacco smoking, alcohol drinking, low levels of intake of fruits and vegetables as well as gastroesophageal reflux and susceptibility genes. Practical Implications A healthy lifestyle including smoking cessation, increasing physical activity, consumption of vegetables as well as reduction of alcohol intake and caloric consumption are major approaches to the prevention of EC. PMID:27722152

Inhibition of Heat-Stable Toxin-Induced Intestinal Salt and Water Secretion by a Novel Class of Guanylyl Cyclase C Inhibitors.

PubMed

Bijvelds, Marcel J C; Loos, Michaela; Bronsveld, Inez; Hellemans, Ann; Bongartz, Jean-Pierre; Ver Donck, Luc; Cox, Eric; de Jonge, Hugo R; Schuurkes, Jan A J; De Maeyer, Joris H

2015-12-01

Many enterotoxigenic Escherichia coli strains produce the heat-stable toxin, STa, which, by activation of the intestinal receptor-enzyme guanylyl cyclase (GC) C, triggers an acute, watery diarrhea. We set out to identify GCC inhibitors that may be of benefit for the treatment of infectious diarrheal disease. Compounds that inhibit STa-induced cyclic guanosine 3',5'-monophosphate (cGMP) production were selected by performing cyclase assays on cells and membranes containing GCC, or the related GCA. The effect of leads on STa/GCC-dependent activation of the cystic fibrosis transmembrane conductance regulator anion channel was investigated in T84 cells, and in porcine and human intestinal tissue. Their effect on STa-provoked fluid transport was assessed in ligated intestinal loops in piglets. Four N-2-(propylamino)-6-phenylpyrimidin-4-one-substituted piperidines were shown to inhibit GCC-mediated cellular cGMP production. The half maximal inhibitory concentrations were ≤ 5 × 10(-7) mol/L, whereas they were >10 times higher for GCA. In T84 monolayers, these leads blocked STa/GCC-dependent, but not forskolin/adenylyl cyclase-dependent, cystic fibrosis transmembrane conductance regulator activity. GCC inhibition reduced STa-provoked anion secretion in pig jejunal tissue, and fluid retention and cGMP levels in STa-exposed loops. These GCC inhibitors blocked STa-provoked anion secretion in rectal biopsy specimens. We have identified a novel class of GCC inhibitors that may form the basis for development of future therapeutics for (infectious) diarrheal disease. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Dietary intake of flavonoids and oesophageal and gastric cancer: incidence and survival in the United States of America (USA).

PubMed

Petrick, J L; Steck, S E; Bradshaw, P T; Trivers, K F; Abrahamson, P E; Engel, L S; He, K; Chow, W-H; Mayne, S T; Risch, H A; Vaughan, T L; Gammon, M D

2015-03-31

Flavonoids, polyphenolic compounds concentrated in fruits and vegetables, have experimentally demonstrated chemopreventive effects against oesophageal and gastric cancer. Few epidemiologic studies have examined flavonoid intake and incidence of these cancers, and none have considered survival. In this USA multicentre population-based study, case participants (diagnosed during 1993-1995 with oesophageal adenocarcinoma (OEA, n=274), gastric cardia adenocarcinoma (GCA, n=248), oesophageal squamous cell carcinoma (OES, n=191), and other gastric adenocarcinoma (OGA, n=341)) and frequency-matched controls (n=662) were interviewed. Food frequency questionnaire responses were linked with USDA Flavonoid Databases and available literature for six flavonoid classes and lignans. Case participants were followed until 2000 for vital status. Multivariable-adjusted odds ratios (ORs) and hazard ratios (HRs) (95% confidence intervals (CIs)) were estimated, comparing highest with lowest intake quartiles, using polytomous logistic and proportional hazards regressions, respectively. Little or no consistent association was found for total flavonoid intake (main population sources: black tea, orange/grapefruit juice, and wine) and incidence or survival for any tumour type. Intake of anthocyanidins, common in wine and fruit juice, was associated with a 57% reduction in the risk of incident OEA (OR=0.43, 95% CI=0.29-0.66) and OES (OR=0.43, 95% CI=0.26-0.70). The ORs for isoflavones, for which coffee was the main source, were increased for all tumours, except OES. Anthocyanidins were associated with decreased risk of mortality for GCA (HR=0.63, 95% CI=0.42-0.95) and modestly for OEA (HR=0.87, 95% CI=0.60-1.26), but CIs were wide. Our findings, if confirmed, suggest that increased dietary anthocyanidin intake may reduce incidence and improve survival for these cancers.

The Incidence of Primary Systemic Vasculitis in Jerusalem: A 20-year Hospital-based Retrospective Study.

PubMed

Nesher, Gideon; Ben-Chetrit, Eli; Mazal, Bracha; Breuer, Gabriel S

2016-06-01

The incidence of primary systemic vasculitides varies among different geographic regions and ethnic origins. The aim of this study was to examine the incidence rates of vasculitides in the Jerusalem Jewish population, and to examine possible trends in incidence rates over a 20-year period. The clinical databases of inpatients at the 2 medical centers in Jerusalem were searched for patients with vasculitis diagnosed between 1990-2009. Individual records were then reviewed by one of the authors. The significance of trends in incidence rates throughout the study period was evaluated by Pearson correlation coefficient. The average annual incidence rate of polyarteritis nodosa was 3.6/million adults (95% CI 1.6-4.7). Incidence rates did not change significantly during this period (r = 0.39, p = 0.088). The incidence of granulomatosis with polyangiitis (GPA) was 4.1 (2.2-5.9) for the whole period, during which it increased significantly (r = 0.53, p < 0.05). The incidence of microscopic polyangiitis (MPA) was lower: 2.3 (1.2-3.5)/million. It also increased significantly (r = 0.55, p < 0.05). The incidence of eosinophilic granulomatosis with polyangiitis was 1.2 (0.4-1.9), which remained stable throughout the study period. The incidence of Takayasu arteritis was 2.1/million (95% CI 1.2-2.9), and it also remained stable. Giant cell arteritis (GCA) incidence was 8.1 (5.7-10.6)/100,000 population aged 50 years or older. In sharp contrast with other vasculitides, its incidence decreased significantly throughout the study period (r = -0.61, p < 0.01). The incidence rates of vasculitides in the Jewish population of Jerusalem are in the lower range of global incidence rates. While GPA and MPA incidence are increasing, GCA incidence is decreasing.

Molecular Physiology of Membrane Guanylyl Cyclase Receptors.

PubMed

Kuhn, Michaela

2016-04-01

cGMP controls many cellular functions ranging from growth, viability, and differentiation to contractility, secretion, and ion transport. The mammalian genome encodes seven transmembrane guanylyl cyclases (GCs), GC-A to GC-G, which mainly modulate submembrane cGMP microdomains. These GCs share a unique topology comprising an extracellular domain, a short transmembrane region, and an intracellular COOH-terminal catalytic (cGMP synthesizing) region. GC-A mediates the endocrine effects of atrial and B-type natriuretic peptides regulating arterial blood pressure/volume and energy balance. GC-B is activated by C-type natriuretic peptide, stimulating endochondral ossification in autocrine way. GC-C mediates the paracrine effects of guanylins on intestinal ion transport and epithelial turnover. GC-E and GC-F are expressed in photoreceptor cells of the retina, and their activation by intracellular Ca(2+)-regulated proteins is essential for vision. Finally, in the rodent system two olfactorial GCs, GC-D and GC-G, are activated by low concentrations of CO2and by peptidergic (guanylins) and nonpeptidergic odorants as well as by coolness, which has implications for social behaviors. In the past years advances in human and mouse genetics as well as the development of sensitive biosensors monitoring the spatiotemporal dynamics of cGMP in living cells have provided novel relevant information about this receptor family. This increased our understanding of the mechanisms of signal transduction, regulation, and (dys)function of the membrane GCs, clarified their relevance for genetic and acquired diseases and, importantly, has revealed novel targets for therapies. The present review aims to illustrate these different features of membrane GCs and the main open questions in this field. Copyright © 2016 the American Physiological Society.

Amyloid-β 11C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials.

PubMed

Liu, Enchi; Schmidt, Mark E; Margolin, Richard; Sperling, Reisa; Koeppe, Robert; Mason, Neale S; Klunk, William E; Mathis, Chester A; Salloway, Stephen; Fox, Nick C; Hill, Derek L; Les, Andrea S; Collins, Peter; Gregg, Keith M; Di, Jianing; Lu, Yuan; Tudor, I Cristina; Wyman, Bradley T; Booth, Kevin; Broome, Stephanie; Yuen, Eric; Grundman, Michael; Brashear, H Robert

2015-08-25

To evaluate the effects of bapineuzumab on brain β-amyloid (Aβ) burden using (11)C-Pittsburgh compound B ((11)C-PiB)-PET. Two phase 3 clinical trials, 1 each in apolipoprotein APOE ε4 carriers and noncarriers, were conducted in patients with mild to moderate Alzheimer disease dementia. Bapineuzumab, an anti-Aβ monoclonal antibody, or placebo, was administered by IV infusion every 13 weeks for 78 weeks. PET substudies assessed change in brain fibrillar Aβ over 71 weeks using an (11)C-PiB-PET standardized uptake value ratio (SUVr) global cortical average (GCA) comprising the average SUVr from 5 cortical regions of interest with cerebellar gray matter as the reference region. A total of 115 carriers and 39 noncarriers were analyzed. The difference (δ) in mean baseline to 71 week change in (11)C-PiB-PET GCA between bapineuzumab and placebo was significant in carriers (0.5 mg/kg vs placebo δ = -0.101; p = 0.004) and in pooled analyses of both carriers and noncarriers (0.5 mg/kg vs placebo δ = -0.068; p = 0.027; 1.0 mg/kg vs placebo δ = -0.133; p = 0.028) but not in the noncarrier trial separately. Analyses by individual region of interest and in mild disease yielded findings similar to the main trial results. The (11)C-PiB-PET imaging results demonstrated reduction of fibrillar Aβ accumulation in patients with Alzheimer disease treated with bapineuzumab; however, as no clinical benefit was observed, the findings are consistent with the hypotheses that bapineuzumab may not have been initiated early enough in the disease course, the doses were insufficient, or the most critical Aβ species were inadequately targeted. © 2015 American Academy of Neurology.

Infrasound signal detection and characterization using ground-coupled airwaves on a single seismo-acoustic sensor pair

NASA Astrophysics Data System (ADS)

McKee, K. F.; Fee, D.; Haney, M. M.; Lyons, J. J.; Matoza, R. S.

2016-12-01

A ground-coupled airwave (GCA) occurs when an incident atmospheric pressure wave encounters the Earth's surface and part of the energy of the wave is transferred to the ground (i.e. coupled to the ground) as a seismic wave. This seismic wave propagates as a surface Rayleigh wave evidenced by the retrograde particle motion detected on a three-component seismometer. Acoustic waves recorded on a collocated microphone and seismometer can be coherent and have a 90-degree phase difference, predicted by theory and in agreement with observations. If the sensors are separated relative to the frequencies of interest, usually 10s to 100s of meters, then recorded wind noise becomes incoherent and an additional phase shift is present due to the separation distance. These characteristics of GCAs have been used to distinguish wind noise from other sources as well as to determine the acoustic contribution to seismic recordings. Here we aim to develop a minimalist infrasound signal detection and characterization technique requiring just one microphone and one three-component seismometer. Based on GCA theory, determining a source azimuth should be possible using a single seismo-acoustic sensor pair by utilizing the phase difference and exploiting the characteristic particle motion. We will use synthetic seismo-acoustic data generated by a coupled Earth-atmosphere 3D finite difference code to test and tune the detection and characterization method. The method will then be further tested using various well-constrained sources (e.g. Chelyabinsk meteor, Pagan Volcano, Cleveland Volcano). Such a technique would be advantageous in situations where resources are limited and large sensor networks are not feasible.

Exploring pima and upland cross-combinations to identify fusarium oxysporum f. sp. vasinfectum race 4 resistant cottons by combining ability of superior cultivars

USDA-ARS?s Scientific Manuscript database

A cotton breeding program strives to identify the best performance cultivars or breeding lines which can be used as parents in crosses. Multi-cross combinations provide the means of performance of each parent and assess the combining ability or productivity of parents through the hybridization proce...

[ROLE OF SLC2A9 AND ABCG2 GENE POLYMORPHISMS IN ORIGIN OF HYPERURICEMIA AND GOUT].

PubMed

Fadieieva, A; Prystupa, L; Pogorelova, O; Kirichenko, N; Dudchenko, I

2016-03-01

The polymorphisms V253I, Q126X, Q141K of SLC2A9 and ABCG2 genes were characterized. GCA и GTC haplotypes of Q126X and Q141K variants can be predictors of gout. The relationship of these polymorphisms with hyperuricaemia according to gender, metabolic syndrome components, with the response to allopurinol was analyzed. It has been established that Q141K polymorphism can directly modulate BCRP-mediated allopurinol and oxypurinol efflux, the K allele is associated with a lower reduction in serum uric acid in response to allopurinol treatment.

Results of the first provisional technical secretariat interlaboratory comparison test

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

Stuff, J.R.; Hoffland, L.

1995-06-01

The principal task of this laboratory in the first Provisional Technical Secretariat (PTS) Interlaboratory Comparison Test was to verify and test the extraction and preparation procedures outlined in the Recommended Operating Procedures for Sampling and Analysis in the Verification of Chemical Disarmament in addition to our laboratory extraction methods and our laboratory analysis methods. Sample preparation began on 16 May 1994 and analysis was completed on 12 June 1994. The analytical methods used included NMR ({sup 1}H and {sup 31}P) GC/AED, GC/MS (EI and methane CI), GC/IRD, HPLC/IC, HPLC/TSP/MS, MS/MS(Electrospray), and CZE.

Micro sized implantable ball lens-based fiber optic probe design

NASA Astrophysics Data System (ADS)

Cha, Jaepyeong; Kang, Jin U.

2014-02-01

A micro sized implantable ball lens-based fiber optic probe design is described for continuous monitoring of brain activity in freely behaving mice. A prototype uses a 500-micron ball lens and a highly flexible 350-micron-diameter fiber bundle, which are enclosed by a 21G stainless steel sheath. Several types and thickness of brain tissue, consisting of fluorescent probes such as GFP, GCaMP3 calcium indicator, are used to evaluate the performance of the imaging probe. Measured working distance is approximately 400-μm, but is long enough to detect neural activities from cortical and cerebellar tissues of mice brain.

Identification of Pro-Differentiation p53 Target Genes and Evaluation of Expression in Normal and Malignant Mammary Gland

DTIC Science & Technology

2008-04-01

genes such as c -myc and Klf-4, frequently upregulated in tumors also have been shown to establish and preserve the ES cell phenotype and the rapid...proliferation of ES cells in culture. More importantly, the introduction of these four factors (Oct3/4, Sox-2, c -myc and Klf-4) into mouse embryonic or...GTA-3’; mouse nanog: sense 5’-AAG TAC CTC AGC CTC CAG CA-3’, antisense 5’-CGT AAG GCT GCA GAA AGT GC-3’; mouse c -myc: sense 5’-CAC CAT GCC CCT CAA CGT

Novel Therapeutic Strategy for the Prevention of Bone Fractures

DTIC Science & Technology

2014-08-01

GAC CTT CAA CAC CCC GTG GCC ATC TCC TGC TCG AAG TC Meredith et al 2011* Mstn ACT GGA CCT CTC GAT AGA ACA CTC ACT TAG TGC TGT GTG TGT GGA GAT...NM_010834.2 IGF-1 CAG ACA GGA GCC CAG GAA AG AAG TGC CGT ATC CCA GAG GA NM_184052 MHC ACA GTC AGA GGT GTG ACTC AGC CG CCG ACT TGC GGA GGA AAG GTG C...AGC AGA GA TGA GTG CCT GCG GTA CAG AT NM_007553.2 RUNX-2 GGA AAG GCA CTG ACT GAC CTA ACA AAT TCT AAG CTT GGG AGG A NM_009820 Osx ACT ACC CAC CCT TCC

Development and Characterization of Novel Bioluminecent Systems

DTIC Science & Technology

2013-07-01

Ppy I108R. The following primers and their respective reverse compliments were used: Y447E, 5´- CT TTA ATT AAA TAC AAA GGA GAG CAG GTG GCC CCC GCT G...3´ [EcoRV] and I108R, 5´- GGA GTT GCA GTG GCG CCC GCG AAC GAC CGT TAT AAT GAA CGT-3´ [KasI] (bold represents the mutated codons, underlined...primers and their respective reverse compliments: Y447C, 5´- G AAG TCT TTA ATA AAA TAC AAA GGA TGT CAG GTG GCC CCC GCT G -3´ [PacI] and I108C, 5´- GGA

Bacteroides Fragilis OmpA: Utility as a Live Vaccine Vector for Biodefense Agents

DTIC Science & Technology

2009-01-01

shared by all four homologs are highlighted in black. Positions where amino acid similarity is shared by all four homologs are highlighted in gray ...study Primers for RT PCR OmpA1-F gga tat gac ggt gtt gcc ag this study OmpA1-R tag cag cag cca tgt cat tc this study OmpA2-F tag aag gtg cat...gga cta ct this study OmpA2-R aac cgc caa tag cat tgg ac this study OmpA3-F act ccg ctg atc aat gtg tc this study OmpA3-R cgt ctg cac gca tag tga ag

Identification and Characterization of Ovarian Carcinoma Peptide Epitopes Recognized by Cytotoxic T Lymphocytes

DTIC Science & Technology

2007-11-01

CCA CAG TGC CCC AGG TTA GAA CGG TCA GCA GAA TAG-2a 62 528 AGC GGC GGG CTG AAG GA GAG GGT AGG GTG GTC ATT GTG TCA TAG-2b 62 401 AGC GGC GGG CTG AAG...GGT AGG GTG GTC ATT GTG TCA TAG-2b 62 401 AGC GGC GGG CTG AAG GAC TC CAG CAC AAC AGG AAC ATT CAG TGG TAB-2c 62 536 AGC GGC GGG CTG AAG GA GGG GGA TTT...Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian

Interplay of Plasma Membrane and Vacuolar Ion Channels, Together with BAK1, Elicits Rapid Cytosolic Calcium Elevations in Arabidopsis during Aphid Feeding[OPEN

PubMed Central

Vincent, Thomas R.; Avramova, Marieta; Canham, James; Higgins, Peter; Bilkey, Natasha; Mugford, Sam T.; Pitino, Marco; Toyota, Masatsugu

2017-01-01

A transient rise in cytosolic calcium ion concentration is one of the main signals used by plants in perception of their environment. The role of calcium in the detection of abiotic stress is well documented; however, its role during biotic interactions remains unclear. Here, we use a fluorescent calcium biosensor (GCaMP3) in combination with the green peach aphid (Myzus persicae) as a tool to study Arabidopsis thaliana calcium dynamics in vivo and in real time during a live biotic interaction. We demonstrate rapid and highly localized plant calcium elevations around the feeding sites of M. persicae, and by monitoring aphid feeding behavior electrophysiologically, we demonstrate that these elevations correlate with aphid probing of epidermal and mesophyll cells. Furthermore, we dissect the molecular mechanisms involved, showing that interplay between the plant defense coreceptor BRASSINOSTEROID INSENSITIVE-ASSOCIATED KINASE1 (BAK1), the plasma membrane ion channels GLUTAMATE RECEPTOR-LIKE 3.3 and 3.6 (GLR3.3 and GLR3.6), and the vacuolar ion channel TWO-PORE CHANNEL1 (TPC1) mediate these calcium elevations. Consequently, we identify a link between plant perception of biotic threats by BAK1, cellular calcium entry mediated by GLRs, and intracellular calcium release by TPC1 during a biologically relevant interaction. PMID:28559475

Rehabilitation-triggered cortical plasticity after stroke: in vivo imaging at multiple scales (Conference Presentation)

NASA Astrophysics Data System (ADS)

Allegra Mascaro, Anna Letizia; Conti, Emilia; Lai, Stefano; Spalletti, Cristina; Di Giovanna, Antonino Paolo; Alia, Claudia; Panarese, Alessandro; Sacconi, Leonardo; Micera, Silvestro; Caleo, Matteo; Pavone, Francesco S.

2017-02-01

Neurorehabilitation protocols based on the use of robotic devices provide a highly repeatable therapy and have recently shown promising clinical results. Little is known about how rehabilitation molds the brain to promote motor recovery of the affected limb. We used a custom-made robotic platform that provides quantitative assessment of forelimb function in a retraction test. Complementary imaging techniques allowed us to access to the multiple facets of robotic rehabilitation-induced cortical plasticity after unilateral photothrombotic stroke in mice Primary Motor Cortex (Caudal Forelimb Area - CFA). First, we analyzed structural features of vasculature and dendritic reshaping in the peri-infarct area with two-photon fluorescence microscopy. Longitudinal analysis of dendritic branches and spines of pyramidal neurons suggests that robotic rehabilitation promotes the stabilization of peri-infarct cortical excitatory circuits, which is not accompanied by consistent vascular reorganization towards pre-stroke conditions. To investigate if this structural stabilization was linked to functional remapping, we performed mesoscale wide-field imaging on GCaMP6 mice while performing the motor task on the robotic platform. We revealed temporal and spatial features of the motor-triggered cortical activation, shining new light on rehabilitation-induced functional remapping of the ipsilesional cortex. Finally, by using an all-optical approach that combines optogenetic activation of the contralesional hemisphere and wide-field functional imaging of peri-infarct area, we dissected the effect of robotic rehabilitation on inter-hemispheric cortico-cortical connectivity.

Quantitative shock stage assessment in olivine and pyroxene bearing meteorites via in situ micro-XRD

NASA Astrophysics Data System (ADS)

McCausland, P. J.; Flemming, R. L.; Izawa, M. R.

2010-12-01

Shock metamorphism is observed in most meteorites and impact structures [1]. Qualitative petrographic observations underpin a shock classification system [1-3] based on the deformation features in common silicates and on textural relations such as the development of maskelynite from feldspars, mobility of sulphides and metal in veins and local Fe-reduction in silicates. Shock deformation of minerals produces streaks (mosaicity) rather than discrete spots in 2D X-ray diffraction patterns, representing the progressive disruption of the crystal lattice into a mosaic of rotated domains [4,5]. Here we use in situ micro-XRD [5,6] to measure the mosaicity of olivine and pyroxene in ordinary chondrites of increasing shock stages S1 to S5 and then apply the method to achondrites with qualitatively low to high shock. X-ray diffraction data were collected in situ on polished thin sections and slab cut surfaces using a Bruker D8 Discover micro X-ray diffractometer [5], operated using CuKα radiation generated at 40 kV and 40 mA with a beam diameter of 500 μm. Diffracted X-rays were recorded with a 2D detector, giving images with information in both the 2-theta and chi dimensions, in which each lattice plane (hkl) will have a diffraction spot or streak lying along an arc in chi of radius 2-theta (hkl). Individual reflections can be indexed and then integrated as a function of chi angle, allowing examination of the peak shape and quantitative analysis of the mosaic peak FWHM along chi. We find that both forsterite and enstatite exhibit greater mosaicity in chi with increasing shock stage: Forsterite chi ranges from <1° for S1 to >6° for S5. Enstatite chi values from the same meteorites show a more subdued growth of streak length with shock state, from ~1° to ~4°. A slab of the olivine shergottite DaG 476 exhibits forsterite mosaicity of 6.9°+/-1.1°, indicating that it has experienced shock stage S5, with shock pressures 30-45 GPa [1,4], consistent with the 40-45 GPa shock pressure estimated for DaG 476 by plagioclase refractive index [7]. These observations show that shock classification -and potentially shock pressure calibration- can be done using in situ XRD mineral data. [1] Stoffler, D. et al., (1991) GCA 55, 3845-3867. [2] Scott, E.R.D. et al., (1992) GCA 56, 4281-4293. [3] Rubin, A.E. et al., (1997) GCA 61, 847-858. [4] Horz, F. and Quiade, W.I. (1973) The Moon 6, 45-86. [5] Flemming, R.L. (2007) Can. Jour. Earth Sci. 44, 1333-1346. [6] Izawa, M.R.M. et al., (2009) LPSC XV. [7] Fritz, J. et al., (2005) MAPS 40, 1393-1411.

Relations between basic and specific motor abilities and player quality of young basketball players.

PubMed

Marić, Kristijan; Katić, Ratko; Jelicić, Mario

2013-05-01

Subjects from 5 first league clubs from Herzegovina were tested with the purpose of determining the relations of basic and specific motor abilities, as well as the effect of specific abilities on player efficiency in young basketball players (cadets). A battery of 12 tests assessing basic motor abilities and 5 specific tests assessing basketball efficiency were used on a sample of 83 basketball players. Two significant canonical correlations, i.e. linear combinations explained the relation between the set of twelve variables of basic motor space and five variables of situational motor abilities. Underlying the first canonical linear combination is the positive effect of the general motor factor, predominantly defined by jumping explosive power, movement speed of the arms, static strength of the arms and coordination, on specific basketball abilities: movement efficiency, the power of the overarm throw, shooting and passing precision, and the skill of handling the ball. The impact of basic motor abilities of precision and balance on specific abilities of passing and shooting precision and ball handling is underlying the second linear combination. The results of regression correlation analysis between the variable set of specific motor abilities and game efficiency have shown that the ability of ball handling has the largest impact on player quality in basketball cadets, followed by shooting precision and passing precision, and the power of the overarm throw.

Influence of Murchison Minerals on Hydrogen-Deuterium Exchange of Amino Acids

NASA Astrophysics Data System (ADS)

Lerner, N. R.

1993-07-01

The amino acids found on the Murchison meteorite are deuterium enriched. For the glycine-alanine fraction, delta D = +2448 per mil, and for the alpha-amino isobutyric acid fraction, delta D = +149 per mil [1]. In order to retain such levels of deuterium enrichment, the amino acids found in Murchison must have not only retained the deuterium enrichment of their interstellar precursors (delta D > +1500 per mil [2]) during synthesis, as has been recently shown [3], but they must have also retained their deuterium label during the aqueous alteration phase [4]. By measuring the rates of deuterium exchange of amino acids with D(sub)2O, limits can be set on the length of time and the conditions under which the Murchison parent body experienced an aqueous environment. The rates of hydrogen-deuterium exchange of nondeuterated glycine, alanine, alpha-amino isobutyric acid, and amino diacetic acid have been measured in D(sub)2O as a function of temperature, pH, and the presence of Murchison minerals. In addition to the amino and carboxylic hydrogens, only the alpha- hydrogens of glycine, alanine, and amino diacetic acid are found to exchange. Even for solutions maintained for weeks at temperatures as high as 120 degrees C, no exchange was observed with the hydrogens of the methyl groups of alanine or alpha-amino isobutyric acid. The rate of exchange for alpha-hydrogens of amino acids is first-order with respect to the amino acid concentration. Increasing the pH of the solution markedly increases the rate of exchange. For example, at 115 degrees C and pH 4.0, 7.0, and 10 the rates are 14, 30, and 125 yr^-1 respectively for glycine and 2.0, 3.5, and 14 yr^-1 respectively for alanine. In a pH-6.0 D(sub)2O solution of amino acids containing Murchison dust the rates are 135 yr^-1 for glycine and 32 yr^-1 for alanine, rates close to those for the pH 10 solution. Activation energies for exchange were obtained from Arrhenius plots constructed from measurements made between 70 degrees C and 155 degrees C in solutions containing Murchison dust. For both glycine and alanine the activation energy is -25 kcal/mole. Using this value, we have calculated the half-lives for complete exchange of the alpha-hydrogens of glycine and alanine for the temperature range thought to have existed on the parent body during aqueous alteration [5]. The half-lives at 0 degrees C and 20 degrees C are 7500 yr and 300 yr respectively for glycine and 55,000 yr and 2100 yr respectively for alanine. Murchison amino acid fraction IV [1] was known to contain impurities and hence the measured delta D value represents a lower limit for alpha-amino isobutyric acid. Assuming that all the deuterium recovered from fraction IV came from alpha-amino isobutryric acid, and that one atom of nitrogen is recovered for each molecule of alpha-amino isobutyric acid, a maximum delta D value of +2600 per mil can be calculated for this amino acid. This is comparable to delta D for the glycine-alanine fraction, which is mainly glycine [6]. In an aqueous environment glycine loses deuterium relatively rapidly while alpha-amino isobutyric acid does not undergo exchange. Hence the similarity in the delta D values of both fractions indicates that the period of aqueous alteration is less than the half-life for hydrogen-deuterium exchange of glycine. References: [1] Pizzarello S. et al. (1991) GCA, 55, 905-910. [2] Zinner E. (1988) In Meteorites and the Early Solar System (J. R. Kerridge and M. S. Matthews, eds.), 956-983, Univ. of Arizona. [3] Lerner N. R. et al. (1993) GCA, in press. [4] Bunch T. E. and Chang S. (1980) GCA, 44, 1543-1577. [5] Clayton R. N. and Mayeda T. K. (1984) EPSL, 67, 151-161. [6] Shock E. L. and Shulte M. D. (1990) GCA, 54, 3159-3173.

Diethylpyrocarbonate and permanganate provide evidence for an unusual DNA conformation induced by binding of the antitumour antibiotics bleomycin and phleomycin.

PubMed Central

Fox, K R; Grigg, G W

1988-01-01

DNA structural changes induced by bleomycin have been investigated using diethylpyrocarbonate and permanganate as probes under conditions in which the antibiotic binds to, but does not cut the DNA. Diethyl-pyrocarbonate shows an enhanced reaction with adenines in the presence of the antibiotic in the sequences GTA greater than GCA greater than GAA, on the 3' side of the drug cutting site (GPy). Permanganate ions display an enhanced reactivity at the second pyrimidine of the sequence GPyPy. The results are consistent with a model in which bleomycin distorts the structure of the base pair on the 3' side of its binding site. Images PMID:2451809

Nrdp1-Mediated ErbB3 Increase during Androgen Ablation and its Contribution to Androgen-Independence

DTIC Science & Technology

2013-04-01

actin-F, 5′-ACT-CTT-CCA-GCC-TTC-GTT-C-3′; β-actin-R, 5′-ATC-TCC-TTC-TGC-ATC-CTG-TC-3′; Nrdp1-F, 5′-GCA- GTG -GAG-TCT-TGG-AGG-AG-3′; Nrdp1-R, 5′-GCC-TTT...60(4):332–337. [PubMed: 15264245] 65. Lara PN Jr. Chee KG, Longmate J, Ruel C, Meyers FJ, Gray CR, Edwards RG, Gumerlock PH, Twardowski P, Doroshow...Lara PN Jr, Chee KG, Longmate J, Ruel C, Meyers FJ, Gray CR, et al. Trastuzumab plus docetaxel in HER-2/neu-positive prostate carcinoma: final results

The Mechanism of Action of Unique Small Molecules that Inhibit the Pim Protein Kinase Blocking Prostate Cancer Cell Growth

DTIC Science & Technology

2010-05-01

shown. (E) Cap-dependent ( gray bars) and IRES-dependent (black bars) translation in MEFs as measured by Renilla and Firefly luciferase activities...AGC ATC AAC C; EPHA2-R, GTG ACC TCG TAC TTC CAC ACT C. HER3-F, CGA TGC TGA GAA CCA ATA CCA G; HER3-R, ATA GCC TGT CAC TTC TCG AAT C. INSR-F, GGA AGT...TAC GTC TGA TTC GAG G; INSR-R, TGA GTG ATG GTG AGG TTG TG. IGF1R-F, CCT GCA CAA CTC CAT CTT CGT G; IGF1R-R, CGG TGA TGT TGT AGG TGT CTG C. EGFR-F

Combining ability of tropical and temperate inbred lines of popcorn.

PubMed

da Silva, V Q R; do Amaral Júnior, A T; Gonçalves, L S A; Freitas Júnior, S P; Candido, L S; Vittorazzi, C; Moterle, L M; Vieira, R A; Scapim, C A

2010-08-31

In Brazil, using combining ability of popcorn genotypes to achieve superior hybrids has been unsuccessful because the local genotypes are all members of the same heterotic group. To overcome this constraint, 10 lines (P(1) to P(10)) with different adaptations to tropical or temperate edaphoclimatic environments were used to obtain 45 F(1) hybrids in a complete diallel. These hybrids and three controls were evaluated in two environments in Rio de Janeiro State. Grain yield (GY), popping expansion (PE), plant height (PH), ear height (EH), and days to silking (FL) were evaluated in randomized complete blocks with three replications. Significant differences between genotypes (P

Driving and driven architectures of directed small-world human brain functional networks.

PubMed

Yan, Chaogan; He, Yong

2011-01-01

Recently, increasing attention has been focused on the investigation of the human brain connectome that describes the patterns of structural and functional connectivity networks of the human brain. Many studies of the human connectome have demonstrated that the brain network follows a small-world topology with an intrinsically cohesive modular structure and includes several network hubs in the medial parietal regions. However, most of these studies have only focused on undirected connections between regions in which the directions of information flow are not taken into account. How the brain regions causally influence each other and how the directed network of human brain is topologically organized remain largely unknown. Here, we applied linear multivariate Granger causality analysis (GCA) and graph theoretical approaches to a resting-state functional MRI dataset with a large cohort of young healthy participants (n = 86) to explore connectivity patterns of the population-based whole-brain functional directed network. This directed brain network exhibited prominent small-world properties, which obviously improved previous results of functional MRI studies showing weak small-world properties in the directed brain networks in terms of a kernel-based GCA and individual analysis. This brain network also showed significant modular structures associated with 5 well known subsystems: fronto-parietal, visual, paralimbic/limbic, subcortical and primary systems. Importantly, we identified several driving hubs predominantly located in the components of the attentional network (e.g., the inferior frontal gyrus, supplementary motor area, insula and fusiform gyrus) and several driven hubs predominantly located in the components of the default mode network (e.g., the precuneus, posterior cingulate gyrus, medial prefrontal cortex and inferior parietal lobule). Further split-half analyses indicated that our results were highly reproducible between two independent subgroups. The current study demonstrated the directions of spontaneous information flow and causal influences in the directed brain networks, thus providing new insights into our understanding of human brain functional connectome.

[Differential concentrations of conjugated bile acids in sera of patients with polypoid lesions of gallbladder].

PubMed

Huang, Peng; Zhao, Meifen; Meng, Fanbin; Sun, Tao; He, Chunxu; Chen, Jingyu; Zhang, Jiali; Huang, Jiapeng; Ge, Chunlin

2014-11-04

To explore the concentration differences of eight conjugated bile acids between patients of cholesterol polyps and adenomatous polyps and determine the differential diagnosis markers for polypoid lesions of gallbladder (PLG). During the period of March 2013 to November, 18 cholesterol polyps patients, 9 adenomatous polyps ones and 20 simple gallstone disease ones were enrolled. High performance liquid chromatography with ultraviolet detection was used to test 8 conjugated bile acids in sera. A total of 8 conjugated bile acids were completely dissociated within 10 minutes and the assay was liner in the range of 3.91 to 500.00 mg/L. The correlation coefficients for linear regression were from 0.995 to 0.999 and the detection limits ranged from 3.91 to 7.81 mg/L. The serum level of glycocholic acid (GCA) in adenomatous polyps group (3.48 ± 1.66) mg/L was significantly higher than that in cholesterol polyps group ((2.16 ± 0.71) mg/L, q = 5.182, P = 0.001) and control group ((2.15 ± 0.45) mg/L, q = 5.313, P = 0.001). The serum level of glycochenodeoxycholic acid (GCDCA) in adenomatous polyps group (12.67 ± 1.74) mg/L was significantly higher than that in cholesterol polyps group ((10.53 ± 3.04) mg/L, q = 3.253, P = 0.026) and control group ((10.72 ± 1.58) mg/L, q = 3.015, P = 0.038). The serum level of taurochenodeoxycholic acid (TCDCA) in adenomatous polyps group ((6.79 ± 2.90) mg/L) was significantly higher than that in cholesterol polyps group ((4.47 ± 2.35) mg/L, q = 3.412, P = 0.020) and control group ((4.72 ± 2.11) mg/L q = 3.091, P = 0.034). The serum levels of GCA, GCDCA and TCDCA in adenomatous polyps patients are higher than those in cholesterol polyps counterparts. And these markers may aid the differential diagnosis of PLG.

Concentration effect on inter-mineral equilibrium isotope fractionation: insights from Mg and Ca isotopic systems

NASA Astrophysics Data System (ADS)

Huang, F.; Wang, W.; Zhou, C.; Kang, J.; Wu, Z.

2017-12-01

Many naturally occurring minerals, such as carbonate, garnet, pyroxene, and feldspar, are solid solutions with large variations in chemical compositions. Such variations may affect mineral structures and modify the chemical bonding environment around atoms, which further impacts the equilibrium isotope fractionation factors among minerals. Here we investigated the effects of Mg content on equilibrium Mg and Ca isotope fractionation among carbonates and Ca content on equilibrium Ca isotope fractionation between orthopyroxene (opx) and clinopyroxene (cpx) using first-principles calculations. Our results show that the average Mg-O bond length increases with decreasing Mg/(Mg+Ca) in calcite when it is greater than 1/48[1] and the average Ca-O bond length significantly decreases with decreasing Ca/(Ca+Mg+Fe) in opx when it ranges from 2/16 to 1/48[2]. Equilibrium isotope fractionation is mainly controlled by bond strengths, which could be measured by bond lengths. Thus, 103lnα26Mg/24Mg between dolomite and calcite dramatically increases with decreasing Mg/(Mg+Ca) in calcite [1] and it reaches a constant value when it is lower than 1/48. 103lnα44Ca/40Ca between opx and cpx significantly increases with decreasing Ca content in opx when Ca/(Ca+Mg+Fe) ranges from 2/16 to 1/48 [2]. If Ca/(Ca+Mg+Fe) is below 1/48, 103lnα44Ca/40Ca is not sensitive to Ca content. Based on our results, we conclude that the concentration effect on equilibrium isotope fractionation could be significant within a certain range of chemical composition of minerals, which should be a ubiquitous phenomenon in solid solution systems. [1] Wang, W., Qin, T., Zhou, C., Huang, S., Wu, Z., Huang, F., 2017. GCA 208, 185-197. [2] Feng, C., Qin, T., Huang, S., Wu, Z., Huang, F., 2014. GCA 143, 132-142.

Source of Volatiles in Earth's Deep Mantle from Neon Isotope Systematics in the South Atlantic

NASA Astrophysics Data System (ADS)

Williams, C. D.; Mukhopadhyay, S.

2016-12-01

The noble gases play an important role in understanding Earth's accretion and subsequent evolution. Neon isotopes in particular have the potential to distinguish between distinct sources of Earth's volatiles e.g., acquisition of nebular gas, solar wind implanted materials or chondritic meteorites and their components. The neon isotopic composition of the deep mantle remains subject to debate with the majority of mantle-derived basalts displaying maximum 20Ne/22Ne ratios less than 12.5, similar to values determined for the convective mantle (20Ne/22Ne = 12.49 +/- 0.04; [1]). These values are also much lower than those of solar wind (20Ne/22Ne = 13.8; [2,3]) and estimates of the nebular gas (20Ne/22Ne = 13.4; [4]) but comparable to solar wind implanted meteoritic materials (20Ne/22Ne = 12.5-12.7; [5]). Here we determine the neon isotopic composition of mantle-derived materials from the south Atlantic. These samples display strong linear correlations in 20Ne/22Ne-21Ne/22Ne space with maximum 20Ne/22Ne ratios that are resolvable from and higher than materials derived from the convecting mantle as well as models of solar wind implantation. These results supplement a growing database of mantle materials characterized by 20Ne/22Ne ratios greater than 12.5, challenging the notion that the entire mantle acquired volatiles from solar wind implanted meteoritic materials. In this presentation we will explore alternative origins for these volatiles and provide testable predictions for each scenario. [1] G. Holland, C.J. Ballentine.. Nature 441 (2006), 186-191. [2] A. Gimberg et al. GCA 72 (2008), 626-645. [3] V.S. Heber et al. GCA 73 (2009), 7414-7432. [4] V. S. Heber et al. ApJ 759 (2012), 121. [5] R. Wieler in: D. Porcelli, C.J. Ballentine, R. Wieler (Eds.), Reviews in Mineralogy and Geochemistry 47 (2002), 21-70.

Predictors of positive 18F-FDG PET/CT-scan for large vessel vasculitis in patients with persistent polymyalgia rheumatica.

PubMed

Prieto-Peña, Diana; Martínez-Rodríguez, Isabel; Loricera, Javier; Banzo, Ignacio; Calderón-Goercke, Mónica; Calvo-Río, Vanesa; González-Vela, Carmen; Corrales, Alfonso; Castañeda, Santos; Blanco, Ricardo; Hernández, José L; González-Gay, Miguel Á

2018-05-18

Polymyalgia rheumatica (PMR) is often the presenting manifestation of giant cell arteritis (GCA). Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan often discloses the presence of large vessel vasculitis (LVV) in PMR patients. We aimed to identify predictive factors of a positive PET/CT scan for LVV in patients classified as having isolated PMR according to well-established criteria. A set of consecutive patients with PMR from a single hospital were assessed. All of them underwent PET/CT scan between January 2010 and February 2018 based on clinical considerations. Patients with PMR associated to other diseases, including those with cranial features of GCA, were excluded. The remaining patients were categorized in classic PMR (if fulfilled the 2012 EULAR/ACR classification criteria at disease diagnosis; n = 84) or atypical PMR (who did not fulfill these criteria; n = 16). Only information on patients with classic PMR was assessed. The mean age of the 84 patients (51 women) with classic PMR was 71.4 ± 9.2 years. A PET/CT scan was positive in 51 (60.7%). Persistence of classic PMR symptoms was the most common reason to perform a PET/CT scan. Nevertheless, patients with positive PET/CT scan often had unusual symptoms. The best set of predictors of a positive PET/CT scan were bilateral diffuse lower limb pain (OR = 8.8, 95% CI: 1.7-46.3; p = 0.01), pelvic girdle pain (OR = 4.9, 95% CI: 1.50-16.53; p = 0.01) and inflammatory low back pain (OR = 4.7, 95% CI: 1.03-21.5; p = 0.04). Inflammatory low back pain, pelvic girdle and diffuse lower limb pain are predictors of positive PET/CT scan for LVV in PMR. Copyright © 2018 Elsevier Inc. All rights reserved.

Pathologic Markers Determining Prognosis in Patients with Treated or Healing Giant Cell Arteritis.

PubMed

Sultan, Harris; Smith, Stacy V; Lee, Andrew G; Chévez-Barrios, Patricia

2018-06-08

To provide quantitative evidence linking the Cluster of Differentiation-68 (CD68)+ macrophage-marker found on temporal artery biopsies (TABs) with disease prognosis. Retrospective, cross-sectional study METHODS: We examined 42 consecutive patients who had undergone unilateral TABs at a single hospital in 2015. Clinical data, laboratory data, and histopathologic features of TABs were recorded. clinical diagnosis of giant cell arteritis (GCA) with TAB performed at the same center. CD68 immunohistochemistry was used to label macrophages in the TABs. multiple logistic regression and bivariate comparisons to measure the association between CD68+ cells per histologic section with placement on immunomodulatory therapy (IMT). Twenty seven patients were females (64%), with a mean age of 72 (standard deviation [S.D.] ±7.7). Eleven patients (26%) were placed on IMT, 17 (40%) had disease recurrence during steroid taper, and 25 (60%) were referred to rheumatology. Of 42 biopsies, 35 underwent staining with CD68 to confirm active inflammation in suspicious, but not diagnostic, specimens. Patients eventually placed on IMT had increased CD68+ cells/slice compared to those not on IMT (median 5.00 [25-75 th quartile 2.00-7.15] vs 1.21 [0.38-2.57], p=0.031, respectively). A receiver operating characteristics (ROC) curve demonstrates that 2.17 CD68+ cells/slice predicts placement on IMT with an odds ratio of 1.54 (95% C.I. 1.02-2.33, p=0.038). Patients refractory to initial steroid tapers and those eventually placed on IMT had increased CD68 cells/section. CD68+ macrophages and their location on the internal elastic lamina may predict disease severity in patients with presumed GCA. Our results suggest that this marker may expedite patient triaging to alternate treatment to the usual steroid therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Interrogating the Effects of Radiation Damage Annealing on Helium Diffusion Kinetics in Apatite

NASA Astrophysics Data System (ADS)

Willett, C. D.; Fox, M.; Shuster, D. L.

2015-12-01

Apatite (U-Th)/He thermochronology is commonly used to study landscape evolution and potential links between climate, erosion and tectonics. The technique relies on a quantitative understanding of (i) helium diffusion kinetics in apatite, (ii) an evolving 4He concentration, (iii) accumulating damage to the crystal lattice caused by radioactive decay[1], and (iv) the thermal annealing of such damage[2],[3], which are each functions of both time and temperature. Uncertainty in existing models of helium diffusion kinetics has resulted in conflicting conclusions, especially in settings involving burial heating through geologic time. The effects of alpha recoil damage annealing are currently assumed to follow the kinetics of fission track annealing (e.g., reference [3]), although this assumption is difficult to fully validate. Here, we present results of modeling exercises and a suite of experiments designed to interrogate the effects of damage annealing on He diffusivity in apatite that are independent of empirical calibrations of fission track annealing. We use the existing experimental results for Durango apatite[2] to develop and calibrate a new function that predicts the effects of annealing temperature and duration on measured diffusivity. We also present a suite of experiments conducted on apatite from Sierra Nevada, CA granite to establish whether apatites with different chemical compositions have the same behavior as Durango apatite. Crystals were heated under vacuum to temperatures between 250 and 500°C for 1, 10, or 100 hours. The samples were then irradiated with ~220 MeV protons to produce spallogenic 3He, the diffusant then used in step-heating diffusion experiments. We compare the results of these experiments and model calibrations to existing models. Citations: [1]Shuster, D., Flowers R., and Farley K., (2006), EPSL 249(3-4), 148-161; [2]Shuster, D. and Farley, K., (2009), GCA 73 (1), 6183-6196; [3]Flowers, R., Ketcham, R., Shuster, D. and Farley, K., (2009), GCA 73, 2347-2365.

Green fluorescent genetically encoded calcium indicator based on calmodulin/M13-peptide from fungi.

PubMed

Barykina, Natalia V; Subach, Oksana M; Piatkevich, Kiryl D; Jung, Erica E; Malyshev, Aleksey Y; Smirnov, Ivan V; Bogorodskiy, Andrey O; Borshchevskiy, Valentin I; Varizhuk, Anna M; Pozmogova, Galina E; Boyden, Edward S; Anokhin, Konstantin V; Enikolopov, Grigori N; Subach, Fedor V

2017-01-01

Currently available genetically encoded calcium indicators (GECIs) utilize calmodulins (CaMs) or troponin C from metazoa such as mammals, birds, and teleosts, as calcium-binding domains. The amino acid sequences of the metazoan calcium-binding domains are highly conserved, which may limit the range of the GECI key parameters and cause undesired interactions with the intracellular environment in mammalian cells. Here we have used fungi, evolutionary distinct organisms, to derive CaM and its binding partner domains and design new GECI with improved properties. We applied iterative rounds of molecular evolution to develop FGCaMP, a novel green calcium indicator. It includes the circularly permuted version of the enhanced green fluorescent protein (EGFP) sandwiched between the fungal CaM and a fragment of CaM-dependent kinase. FGCaMP is an excitation-ratiometric indicator that has a positive and an inverted fluorescence response to calcium ions when excited at 488 and 405 nm, respectively. Compared with the GCaMP6s indicator in vitro, FGCaMP has a similar brightness at 488 nm excitation, 7-fold higher brightness at 405 nm excitation, and 1.3-fold faster calcium ion dissociation kinetics. Using site-directed mutagenesis, we generated variants of FGCaMP with improved binding affinity to calcium ions and increased the magnitude of FGCaMP fluorescence response to low calcium ion concentrations. Using FGCaMP, we have successfully visualized calcium transients in cultured mammalian cells. In contrast to the limited mobility of GCaMP6s and G-GECO1.2 indicators, FGCaMP exhibits practically 100% molecular mobility at physiological concentrations of calcium ion in mammalian cells, as determined by photobleaching experiments with fluorescence recovery. We have successfully monitored the calcium dynamics during spontaneous activity of neuronal cultures using FGCaMP and utilized whole-cell patch clamp recordings to further characterize its behavior in neurons. Finally, we used FGCaMP in vivo to perform structural and functional imaging of zebrafish using wide-field, confocal, and light-sheet microscopy.

Zircon: Free Energy of Formation by Aqueous Solubility Measurements at High T and P

NASA Astrophysics Data System (ADS)

Newton, R. C.; Manning, C. E.; Hanchar, J. M.

2002-12-01

We measured the silica solubility at 800 °C, 12 kbar, of small (~0.5 mg) limpid euhedral zircon crystals grown by a flux-melt method (Hanchar et al., Am. Min., 86, 667, 2001). Incongruent solution occurs according to ZrSiO4 = ZrO2 + SiO2,aq. Zircon lost ~0.1 mg after exposure of 1-2 mg of zircon to ~32 mg H2O in welded Pt envelopes for 90-120 hr in piston-cylinder apparatus using NaCl-graphite furnaces. The average solubility was 0.0645+/-0.007 molal (m), or a mole fraction (XS) of 0.00116. Reversibility was established by rerunning the baddeleyite-coated zircons with a fluid initially slightly SiO2-oversaturated, as determined by the forward experiments, resulting in weight gains of the composite crystals. Similar runs on sintered ZrO2 compacts yielded spontaneous surface nucleation and growth of zircons up to 1 mm. Concentrations were corrected for a small, measured solubility of ZrO2 (0.001 m). Nonideality of aqueous silica was calculated assuming that SiO2,aq consists of a mixture of monomers and dimers (Zotov and Keppler (Chem. Geol., 184, 71, 2002; Newton and Manning, GCA, in press). Our zircon solubility and that of quartz at the same conditions (XS=0.02634, Manning, GCA, 58, 4831, 1994) give activity coefficients at the two concentrations of 0.730 and 0.255, respectively. The activity coefficients and concentrations yield the free energy of formation of zircon from the oxides at 800 °C, 12 kbar of -18.46+/-0.96 kJ/mol, which translates to -11.91+/-0.96 kJ/mol at 800 °C, 1 bar. Our value is compatible with previous estimates based on experiment (Schuiling et al., Am. Min., 61, 166, 1976) and high-T oxide-melt calorimetry (Ellison and Navrotsky, J. Am. Ceram. Soc., 75, 1430, 1992), but is four times more precise than these estimates.

Tracing fluid transfer across subduction zones using iron and zinc stable isotopes

NASA Astrophysics Data System (ADS)

Williams, H. M.; Debret, B.; Pons, M. L.; Bouilhol, P.

2016-12-01

In subduction zones, serpentinite devolatilization within the downgoing slab and the fluids released play a fundamental role in volatile transfer as well as the redox evolution of the sub-arc mantle. Constraining subduction-related serpentinite devolatilisation is essential in order to better understand of the nature and composition of slab-derived fluids and fluid/rock interactions. Fe and Zn stable isotopes can trace fluid composition and speciation as isotope partitioning is driven by changes in oxidation state, coordination, and bonding environment. In the case of serpentinite devolatilisation, Fe isotope fractionation should reflect changes in Fe redox state and the formation of Fe-Cl- and SO42- complexes (Hill et al., GCA 2010); Zn isotope fractionation should be sensitive to complexation with CO32-, HS- and SO42- anions (Fujii et al., GCA 2011). We targeted samples from Western Alps ophiolite complexes, interpreted as remnants of serpentinized oceanic lithosphere metamorphosed and devolatilized during subduction (Hattori and Guillot, G3 2007; Debret et al., Chem. Geol. 2013). A striking negative correlation is present between bulk serpentinite Fe isotope composition and Fe3+/Fetot, with the highest grade samples displaying the heaviest Fe isotope compositions and lowest Fe3+/Fetot (Debret et al., Geology, 2016). The same samples also display a corresponding variation in Zn isotopes, with the highest grade samples displaying isotopically light compositions (Pons et al., in revision). The negative correlation between Fe and Zn isotopes and decrease in Fe3+/Fetot can explained by serpentinite sulfide breakdown and the release of fluids enriched in isotopically light Fe and heavy Zn sulphate complexes. The migration of these SOX-bearing fluids from the slab to the slab-mantle interface or mantle wedge has important implications for the redox evolution of the sub-arc mantle and the transport of metals from the subducting slab.

VTCdb: a gene co-expression database for the crop species Vitis vinifera (grapevine).

PubMed

Wong, Darren C J; Sweetman, Crystal; Drew, Damian P; Ford, Christopher M

2013-12-16

Gene expression datasets in model plants such as Arabidopsis have contributed to our understanding of gene function and how a single underlying biological process can be governed by a diverse network of genes. The accumulation of publicly available microarray data encompassing a wide range of biological and environmental conditions has enabled the development of additional capabilities including gene co-expression analysis (GCA). GCA is based on the understanding that genes encoding proteins involved in similar and/or related biological processes may exhibit comparable expression patterns over a range of experimental conditions, developmental stages and tissues. We present an open access database for the investigation of gene co-expression networks within the cultivated grapevine, Vitis vinifera. The new gene co-expression database, VTCdb (http://vtcdb.adelaide.edu.au/Home.aspx), offers an online platform for transcriptional regulatory inference in the cultivated grapevine. Using condition-independent and condition-dependent approaches, grapevine co-expression networks were constructed using the latest publicly available microarray datasets from diverse experimental series, utilising the Affymetrix Vitis vinifera GeneChip (16 K) and the NimbleGen Grape Whole-genome microarray chip (29 K), thus making it possible to profile approximately 29,000 genes (95% of the predicted grapevine transcriptome). Applications available with the online platform include the use of gene names, probesets, modules or biological processes to query the co-expression networks, with the option to choose between Affymetrix or Nimblegen datasets and between multiple co-expression measures. Alternatively, the user can browse existing network modules using interactive network visualisation and analysis via CytoscapeWeb. To demonstrate the utility of the database, we present examples from three fundamental biological processes (berry development, photosynthesis and flavonoid biosynthesis) whereby the recovered sub-networks reconfirm established plant gene functions and also identify novel associations. Together, we present valuable insights into grapevine transcriptional regulation by developing network models applicable to researchers in their prioritisation of gene candidates, for on-going study of biological processes related to grapevine development, metabolism and stress responses.

The influence of temperature and salinity on the Li/Ca and d7Li of inorganic and biogenic carbonates

NASA Astrophysics Data System (ADS)

Marriott, C.; Staubwasser, M.; Crompton, R.; Henderson, G.

2003-04-01

Lithium is the sixth most abundant metal in the ocean. It is conservative with a residence time of around 1Ma and has two stable isotopes ^7Li and ^6Li that are not actively involved in biological processes. Isotopic fractionation is observed during incorporation into calcium carbonate but no previous work has systematically examined the controls on this fractionation. We have investigated Li incorporation and isotopic fraction in both inorganically precipitated calcite and coralline aragonite (1). In both cases there is an inverse correlation of Li concentration with temperature and no significant variation in isotopic fractionation. A decrease in D Li/Ca from 0.0092 to 0.0030 is seen over a temperature range of 5--30^oC, whilst an offset of approximately -8.5 ppm is seen in the δ^7Li ratio relative to the growth solution. The temperature dependence of Li/Ca has an increased sensitivity at low temperatures and might therefore be useful in examining changes in bottom water temperature. We are now investigating Li/Ca and δ^7Li of foraminifera. Previous work (2) has suggested little variability in Li/Ca with temperature, although this was for samples from warmer water where Li/Ca is not sensitive. In this study, Uvigerina are examined in a series of core top samples from the Arabian Sea with a depth range of 95--1800m and corresponding temperature range of 5--20^oC. A series of inorganic calcite samples have also been precipitated in order to examine the effect of salinity on Li/Ca, δ^7Li and δ44Ca over a salinity range of 10--50 psu. The distribution coefficient of Li shows a positive correlation with salinity over this range. δ^7Li and δ44Ca measurements for these samples are presently being analysed. (1) Marriott et al., 2002, GCA, 66, A485 (2) Delaney et al., 1985, GCA, 49, 1327

Shared-environmental contributions to high cognitive ability.

PubMed

Kirkpatrick, Robert M; McGue, Matt; Iacono, William G

2009-07-01

Using a combined sample of adolescent twins, biological siblings, and adoptive siblings, we estimated and compared the differential shared-environmentality for high cognitive ability and the shared-environmental variance for the full range of ability during adolescence. Estimates obtained via multiple methods were in the neighborhood of 0.20, and suggest a modest effect of the shared environment on both high and full-range ability. We then examined the association of ability with three measures of the family environment in a subsample of adoptive siblings: parental occupational status, parental education, and disruptive life events. Only parental education showed significant (albeit modest) association with ability in both the biological and adoptive samples. We discuss these results in terms of the need for cognitive-development research to combine genetically sensitive designs and modern statistical methods with broad, thorough environmental measurement.

In situ, spatially resolved biosignature detection at the microbial scale

NASA Astrophysics Data System (ADS)

Williford, K. H.; Eigenbrode, J. L.; Hallmann, C.; Kitajima, K.; Kozdon, R.; Summons, R. E.; Kudryavstev, A.; Lepot, K.; Schopf, J.; Spicuzza, M.; Sugitani, K.; Ushikubo, T.; van Kranendonk, M.; Valley, J. W.

2013-12-01

Whether life has ever existed beyond Earth is one of the great human questions. The Science Definition Team (SDT) for the proposed NASA Mars 2020 rover mission recently announced a suggested approach for NASA to 'demonstrate significant technical progress towards the future return of scientifically selected, well-documented samples to Earth' in part 'to investigate whether Mars was ever inhabited by microbial life.' The SDT further recommended a per-sample volume of 8 cm3 [1] (e.g., a core with a diameter of 1 cm and length of 10 cm). Such samples would be the first available for scientific inquiry with the potential to definitively answer the fundamental question of astrobiology, and their small volume would necessitate analysis with non- or minimally destructive techniques. Potential biosignatures include 'chemical, isotopic, mineralogical, and morphological features that can be created by life and also appear to be inconsistent with nonbiological processes'[1]. Guidelines for biosignature detection in extraterrestrial samples derive in part from the search for evidence of life in the most ancient sedimentary rocks on Earth, wherein the most compelling case for biogenicity is made when these 'chemical, isotopic, mineralogical, and morphological features' occur in association. Sedimentary rocks deposited on Earth prior to ~3.5 billion years ago (i.e., when persistent surface water [e.g., 2] likely supported habitable environments on Mars) have only very rarely escaped severe alteration by metamorphism and metasomatism. Understanding how these processes have operated on Earth through strategic interrogation of biosignature alteration records in (meta)sedimentary rocks is thus a critical task in the search for extraterrestrial life. Here we present techniques for and results of in situ, spatially resolved, non- or minimally destructive detection of morphological, elemental, molecular, and light stable isotopic biosignatures, as well as records of alteration, in Precambrian sedimentary rocks from Earth in the context of the eventual analysis of samples returned from Mars. Sample acquisition and preparation, morphological analysis by conventional light, confocal laser, and electron microscopy, elemental analysis by energy and wavelength dispersive spectroscopy, molecular analysis by laser Raman microscopy, carbon isotope analysis of organic matter and carbonate minerals, and multiple sulfur isotope analysis of pyrite with secondary ion mass spectrometry will be discussed. New and recently published [3-5] results from the application of these methods towards detection of the signatures of life, environment, and alteration history in rocks containing putative and bona fide microfossils ranging in age from 0.6 to 3.5 billion years, and in rocks of similar age lacking morphological biosignatures, as well as our current understanding of key challenges and opportunities for future research will be reviewed. [1] Mustard, J.F. et al. 2013. Report of the Mars 2020 Science Definition Team, 154 pp., posted by MEPAG at http://mepag.jpl.nasa.gov/reports/MEP/Mars_2020_SDT_Report_Final.pdf. [2] Williams, R.M.E. et al. 2013. Science 340: 1068-1072. [3] Williford, K.H. et al. 2011. GCA 75: 5686-5705. [4] Williford, K.H. et al. 2013. GCA 104: 165-182. [5] Lepot, K. et al. 2013. GCA 112: 66-86.

Exploring Hydrofluorocarbons as Groundwater Age Tracers (Invited)

NASA Astrophysics Data System (ADS)

Haase, K. B.; Busenberg, E.; Plummer, L. N.; Casile, G.; Sanford, W. E.

2013-12-01

Groundwater dating tracers are an essential tool for analyzing hydrologic conditions in groundwater systems. Commonly used tracers for dating post-1940's groundwater include sulfur hexafluoride (SF6), chlorofluorocarbons (CFCs), 3H-3He, and other isotopic tracers (85Kr, δ2H and δ18O isotopes, etc.). Each tracer carries a corresponding set of advantages and limitations imposed by field, analytical, and interpretive methods. Increasing the number available tracers is appealing, particularly if they possess inert chemical properties and unique temporal emission histories from other tracers. Atmospherically derived halogenated trace gases continue to hold untapped potential for new tracers, as they are generally inert and their emission histories are well documented. SF5CF3, and CFC-13 were previously shown to have application as dating tracers, though their low mixing ratios and low solubility require large amounts of water to be degassed for their quantification. Two related groups of compounds, hydrochlorofluorocarbons (HCFCs) and hydrofluorocarbons (HFCs) are hypothesized to be potential age tracers, having similar mixing ratios to the CFCs and relatively high solubility. However, these compounds yield gas chromatography electron capture detector (GC-ECD) responses that are 10-2 -10-5 less than CFC-12, making purge and trap or field stripping GC-ECD approaches impractical. Therefore, in order to use dissolved HCFCs and HFCs as age tracers, different approaches are needed. To solve this problem, we developed an analytical method that uses an atomic emission detector (GC-AED) in place of an ECD to detect fluorinated compounds. In contrast to the ECD, the AED is a universally sensitive, highly linear, elementally specific detector. The new GC-AED system is being used to measure chlorodifluoromethane (HCFC-22), 1,1,1,2-tetrafluoroethane (HFC-134a), and other fluorinated compounds in one liter water samples to study their potential as age dating tracers. HCFC-22 is a refrigerant introduced in the 1940's, with atmospheric mixing ratios increasing through the 1990s to the present value of ≈230 pptv. HFC-134a is typically is used as a chlorine-free replacement for CFC-12, finding use in air-condition systems and as an inert aerosol blowing agent, with a mixing ratio that has increased from <1 in 1994 to ≈75 pptv at present (2013). Their unique atmospheric histories and chemistry compared to CFCs makes these compounds interesting age tracer candidates, particularly in situations where multiple tracers enhance interpretive value. For instance, inclusion in lumped parameter mixing models and in situations where SF6 or the CFCs are present in elevated concentrations from non-atmospheric sources such that they cannot be used for dating purposes. Analysis of standards, air equilibrated water, and blanks suggests the GC-AED system is capable of detecting concentrations ≈200 fM (HCFC-22) and ≈100 fM (HFC-134a), corresponding to piston flow ages of 54 and 18 yr, respectively, with a typical uncertainty of ≈1 yr. Preliminary comparisons with CFC and SF6 analyses show general agreement between the techniques (within a few years), and ongoing intercomparison studies will be discussed.

Sources and Contributions of Oxygen During Microbial Pyrite Oxidation: the Triple Oxygen Isotopes of Sulfate

NASA Astrophysics Data System (ADS)

Ziegler, K.; Coleman, M. L.; Mielke, R. E.; Young, E. D.

2008-12-01

The triple isotopes of oxygen (Δ17O' = δ17O'-0.528 × δ18O' using logarithmic deltas) can trace the oxygen sources of sulfate produced during sulfide oxidation, an important biogeochemical process on Earth's surface and possibly also on Mars [1]. δ18OSO4 compositions are determined by the isotopic selectivity of the mechanism(s) responsible for their changes, and the δ18O value of the reactants (O2 vs. H2O). The relative proportional importance and contribution of each of those sources and mechanisms, as well as their associated isotopic fractionations, are not well understood. We are investigating the use of Δ 17O as a quantitative and qualitative tracer for the different processes and oxygen sources involved in sulfate production. Δ17O signatures are distinct fingerprints of these reservoirs, independent of fractionation factors that can be ambiguous. We conducted controlled abiotic and biotic (Acidithiobacillus ferrooxidans, A.f.) laboratory experiments in which water was spiked with 18O, allowing us to quantify the sources of sulfate oxygen and therefore the processes attending sulfate formation. Results of this Δ17O tracer study show that A.f. microbes initiate pyrite S-oxidation within hours of exposure, and that sulfate is produced from ~90% atmospheric oxygen. This initial lag-phase (< 3 days) is characterized by subtle and multiple changes in oxygen source and contribution that is likely due to the adjustment of the microbial metabolism from S to Fe2+-oxidation. A more detailed understanding of the microbial mechanisms and behavior in the initial lag-phase will aid in the understanding of the ecological conditions required for microbial populations to establish and survive. An exponential phase of growth, facilitated by microbial Fe2+-oxidation, follows. The source of sulfate rapidly switches to abiotic sulfide oxidation during exponential growth and the source of oxygen switches from atmospheric O2 to nearly ~100% water. Pending acquisition of complimentary chemistry data (in progress), we interpret our isotope data to indicate that the biotic fractionation factor ɛ18OSO4-O2 of at least ~ -25 to - 35‰ is augmented by microbially induced kinetic fractionation; it is larger than expected based on published equilibrium values [2,3,4]. Our inferred ɛ18OSO4-H2O of at least ~+10‰ is similar to some reported values. These new insights into the close links between microbial life cycle and sources of sulfate oxygen during sulfide oxidation, and their oxygen isotopic expressions, will help elucidate the role of microbial oxidation in natural systems. If microbial populations in natural systems remain in a perpetual lag-phase due to constrains of chemistry, atmospheric oxygen will imprint its isotopic signature onto sulfate deposits. Ultimately, such data could be used as biosignatures on Early Earth or Mars. [1] Brunner and Coleman (2008) EPSL 270, 63-72. [2] Balci et al. (2007) GCA 71, 3796-3811. [3] Pisapia et al. (2007) GCA 71, 2474-2490. [4] Taylor et al. (1984) GCA 48, 2669-2678.

Catalytic synthesis of biologically important metabolites from formaldehyde and ammonia as a putative way of their prebiotic emergence

NASA Astrophysics Data System (ADS)

Delidovich, Irina; Taran, Oxana; Simonov, Alexander; Parmon, Valentin

The modern `RNA-world' theory considering the primary life as a system of self-replicating informational and catalytic oligomers is the most widespread hypothesis of life's origin. At the same time an alternative major theory antithetic to the genetic one exists. It is based on the primary formation of important metabolites and building blocks of biopolymers and appearance of the primordial autocatalytic cycles in geochemical environment. [1]. Encouraged by this theory, we suggest the putative emergence pathways to biologically relevant metabolites from simple precursors: formaldehyde (FA) and ammonia, which are known to be present in the interstellar space [2]. Based on our earlier [3, 4] and novel findings as well as on the literature data [5, 6] the scheme of conjugate autocatalytic processes including photochemical condensation of FA yielding C-C bond and catalytic formation of pyruvaldehyde, pyruvic acid, sugars, aminoacids catalyzed by minerals (aluminum silicate, phoshates) and by aminoacids themselves is proposed. Acetaldehyde, glyoxal, glycol-and glyceraldehydes (GA and GCA) were identified in this work as products of photolysis of FA aqueous solution with summary selectivity up to 20% and can serve as substrates for the synthesis of more complex organic compounds. In turn, alanine and pyruvic acid are formed during UV-irradiation of aqueous solution of acetaldehyde and ammonium nitrate [6]. Pyruvaldehyde formation from GCA and FA in presence of amino acids was observed by A. Weber [5]. Finally, we revealed the catalytic activity of zeolite HZSM-5-17 in acid form towards formation of pyruvaldehyde from GA and GCA in presence of alanine with the yield about 5%. This observation indicates that the assumption of catalytic activity of silica-alumina towards the synthesis of metabolites could be realistic. Prebiotic synthesis of sugars from lower monosacharides, as we showed earlier, could take place over phosphate catalysts [4]. The substrates and the products of the proposed scheme were detected in the interstellar space and meteorites [7, 8], evidencing of the possibility of its realization either on the Protoeath or in the protoplanet disk supplying the initial compounds for contemporary metabolism. Acknowledgements. The financial support of Program RAS, IP SB RAS N 10 is gratefully acknowledged. References 1. A. Eschenmoser, in "Origin of life. Chemical approach", Eds. P. Herdewijn, M.V. Kisakurek, Wiley-VCH, placeCityZurich, 2008 and refs therein. 2. D.A. Williams, J. Phys. Conf. 6, 1-17, 2005. 3. Pestunova, O., Simonov, A., Snytnikov, V., et al., Adv. Space Res. 36/2, 214-219, 2005. 4. Simonov, A., Pestunova, O., Matvienko, L., et al., Adv. Space Res. 40, 1634-1640, 2007. 5. A.L. Weber, Orig. Life Evol. Biosph. 31, 71-86, 2001. 6. T.A. Telegina, et. al., Journ. Evol. Biochim. i Fiziol. (Rus). 4/8, 429-434, 1977. 7. Hollis, J., Jewell, P., Lovas, F., et al., The Astrophysical Journal 613, L45-L48, 2004 8. Cooper, G., Kimmich, N., Belisle, W., et al., Nature 414(6866), 879, 2001.

Metal/Silicate Partitioning, Melt Speciation, Accretion, and Core Formation in the Earth

NASA Astrophysics Data System (ADS)

Drake, M. J.; Hillgren, V. J.; Dearo, J. A.; Capobianco, C. J.

1993-07-01

Core formation in terrestrial planets was concomitant with accretion. Siderophile and chalcophile element signatures in the mantles of planets are the result of these processes. For Earth, abundances of most siderophile and chalcophile elements are elevated relative to predictions from simple metal/silicate equilibria at low pressures [1]. This observation has led to three hypotheses for how these abundances were established: heterogeneous accretion [2], inefficient core formation [3], and metal/silicate equilibria at magma ocean pressures and temperatures [4]. Knowledge of speciation of siderophile elements in silicate melts in equilibrium with metal may help distinguish between these hypotheses. But there is some uncertainty regarding speciation. For example, Ni and Co have been reported to be present as 1+ or zero valence species in silicate melts at redox states appropriate to planetary accretion, rather than the expected 2+ state [5-7]. Independent metal/silicate partitioning experiments by three members of this group using two different experimental designs on both synthetic and natural compositions do not show evidence for Ni and Co in valence states other than 2+ over a wide range of redox states. For example, solid metal/silicate melt partition coefficients for Ni at 1260 degrees C obtained by VJH from experiments investigating the partitioning of Ni, Co, Mo, W, and P are indistinguishable from those obtained by JAD in similar experiments investigating the partitioning of Ni, Ge, and Sn. Both datasets define a line with the equation: log D(Ni) = - 0.54log fO2 - 3.14 with r^2 > 0.995. (Note that fO2 was calculated in both studies from thermodynamic data and phase compositions. A small, systematic offset from the true fO2 as measured by a solid electrolyte cell affects both equations similarly, but does not diminish their close agreement.) The valence of Ni in the silicate melt is obtained by multiplying the slope of the line by -4, indicating divalent Ni in both studies. Experiments by [8] between 1300 degrees C and 1550 degrees C and fO2 from air to just below iron-wustite in which Ni and Co are partitioned between Pt metal and CaO-Al2O3-SiO2 silicate melt also show evidence only for 2+ valence. Capobianco et al. [1] have noted that reliable extrapolation from current laboratory temperatures (1190 degrees C-1600 degrees C) to magma ocean temperatures is not possible. The hypothesis that siderophile and chalcophile element abundances in the mantle of Earth were established by metal/silicate equilibria at magma ocean pressures and temperatures needs to be tested using direct experimental measurements at magma ocean temperatures and pressures. Such experiments are currently being conducted. References: [1] Capobianco et al. (1993) J. Geophys. Res., 98, 5433. [2] Wanke (1981) Phil. Trans. R. Soc. London, A303, 287. [3] Jones and Drake (1986) Nature, 322, 221. [4] Murthy (1991) Science, 253, 303. [5] Schmitt et al. (1989) GCA, 53, 173. [6] Ehlers et al. (1993) GCA, 56, 3733. [7] Colson (1992) Nature, 357, 65. [8] Capobianco and Amelin (1993) GCA, 56 (in press).

Nitrogen in Interplanetary Dust Particles

NASA Astrophysics Data System (ADS)

Keller, L. P.; Thomas, K. L.; Bradley, J. P.; McKay, D. S.

1995-09-01

Little is known about the abundance, distribution and chemical state of nitrogen in IDPs with the exceptions of the isotopic enrichment in 15N displayed by many particles [1-3], and the inferred association of nitrogen with polyaromatic hydrocarbons in some IDPs [4]. Like carbon, nitrogen is strongly fractionated among meteoritic materials and it is well known that the most primitive carbon-rich meteorites also tend to have high nitrogen abundances [5]. Nitrogen-bearing compounds are also a significant component of the carbonaceous material (CHON particles) sampled during the comet Halley encounter [e.g. 6]. We describe here the first reported detection and location of nitrogen concentrations in several IDPs using electron energy-loss spectroscopy. Three chondritic, anhydrous IDPs (L2011R11, L2008F13, and a fragment from L2006, cluster 14) were embedded in sulfur [7] and tranmission electron microscope (TEM) specimens were prepared by ultramicrotomy. The IDP thin sections were placed on copper TEM grids with SiO thin film substrates and analyzed using a JEOL 2010 TEM equipped with a thin-window energy-dispersive X-ray detector and a Gatan 666 parallel EELS spectrometer. We also analyzed W7027H14, a carbon-rich, chondritic-porous IDP that was embedded in epoxy. The EELS data from carbon-rich amorphous regions of the analyzed IDPs typically show a small, but distinct nitrogen edge at ~400 eV (Figure 1). The nitrogen is not homogeneously distributed in the carbonaceous material in the four IDPs analyzed to date, but occurs in "hot spots". However, these "hot spots" do not appear to be associated with a distinct N-bearing mineral (e.g. nitrides); the nitrogen is indigenous to the carbonaceous material in these IDPs. Although the quantitative N analyses using EELS are still in progress, the preliminary data from one IDP (L2011R11) indicates an upper N/C atom ratio of ~0.1, which is comparable to the chondritic value (N/C ~0.08, [8]). It should be noted however, that the SEM/EDX analysis of L2011R11 shows that it has a bulk C abundance of ~9 wt.% (nearly 3X the CI abundance), which indicates that, for this particle, the absolute N abundance is also enriched above CI levels. EELS is well-suited for this analysis because of its sensitivity for light element detection and quantification, and also for the additional data on bonding environment that can be deduced from the near-edge structure. References: [1] Stadermann F. J. et al. (1989) Meteoritics, 24, 327. [2] Stadermann F. J. et al. (1990) LPS XXI, 1190. [3] Messenger S. et al., this volume. [4] Clemett S. J. et al. (1993) Science, 262, 721. [5] Kerridge J. F. (1985) GCA, 49, 1707. [6] Fomenkova M. N. et al. (1994) GCA, 58, 4503. [7] Bradley J. P. et al. (1993) LPS XXIV, 173. [8] Anders E. and Grevesse N. (1989) GCA, 53, 197. FIGURE 1. Electron energy-loss data from carbonaceous material in L2011R11 (a pyroxene-rich, anhydrous IDP) showing detectable nitrogen associated with carbon. The lower spectrum is a 2nd difference spectrum of the raw data.

Cognitive factors affecting children's nonsymbolic and symbolic magnitude judgment abilities: A latent profile analysis.

PubMed

Chew, Cindy S; Forte, Jason D; Reeve, Robert A

2016-12-01

Early math abilities are claimed to be linked to magnitude representation ability. Some claim that nonsymbolic magnitude abilities scaffold the acquisition of symbolic (Arabic number) magnitude abilities and influence math ability. Others claim that symbolic magnitude abilities, and ipso facto math abilities, are independent of nonsymbolic abilities and instead depend on the ability to process number symbols (e.g., 2, 7). Currently, the issue of whether symbolic abilities are or are not related to nonsymbolic abilities, and the cognitive factors associated with nonsymbolic-symbolic relationships, remains unresolved. We suggest that different nonsymbolic-symbolic relationships reside within the general magnitude ability distribution and that different cognitive abilities are likely associated with these different relationships. We further suggest that the different nonsymbolic-symbolic relationships and cognitive abilities in combination differentially predict math abilities. To test these claims, we used latent profile analysis to identify nonsymbolic-symbolic judgment patterns of 124, 5- to 7-year-olds. We also assessed four cognitive factors (visuospatial working memory [VSWM], naming numbers, nonverbal IQ, and basic reaction time [RT]) and two math abilities (number transcoding and single-digit addition abilities). Four nonsymbolic-symbolic ability profiles were identified. Naming numbers, VSWM, and basic RT abilities were differentially associated with the different ability profiles and in combination differentially predicted math abilities. Findings show that different patterns of nonsymbolic-symbolic magnitude abilities can be identified and suggest that an adequate account of math development should specify the inter-relationship between cognitive factors and nonsymbolic-symbolic ability patterns. Copyright © 2016 Elsevier Inc. All rights reserved.

The Zebrafish Ortholog of TRPV1 Is Required for Heat-Induced Locomotion

PubMed Central

Gau, Philia; Poon, Jason; Ufret-Vincenty, Carmen; Snelson, Corey D.; Gordon, Sharona E.; Raible, David W.

2013-01-01

The ability to detect hot temperatures is critical to maintaining body temperature and avoiding injury in diverse animals from insects to mammals. Zebrafish embryos, when given a choice, actively avoid hot temperatures and display an increase in locomotion similar to that seen when they are exposed to noxious compounds such as mustard oil. Phylogenetic analysis suggests that the single zebrafish ortholog of TRPV1/2 may have arisen from an evolutionary precursor of the mammalian TRPV1 and TRPV2. As opposed to TRPV2, mammalian TRPV1 is essential for environmentally relevant heat sensation. In the present study, we provide evidence that the zebrafish TRPV1 ion channel is also required for the sensation of heat. Contrary to development in mammals, zebrafish TRPV1+ neurons arise during the first wave of somatosensory neuron development, suggesting a vital importance of thermal sensation in early larval survival. In vitro analysis showed that zebrafish TRPV1 acts as a molecular sensor of environmental heat (≥25°C) that is distinctly lower than the sensitivity of the mammalian form (≥42°C) but consistent with thresholds measured in behavioral assays. Using in vivo calcium imaging with the genetically encoded calcium sensor GCaMP3, we show that TRPV1-expressing trigeminal neurons are activated by heat at behaviorally relevant temperatures. Using knock-down studies, we also show that TRPV1 is required for normal heat-induced locomotion. Our results demonstrate for the first time an ancient role for TRPV1 in the direct sensation of environmental heat and show that heat sensation is adapted to reflect species-dependent requirements in response to environmental stimuli. PMID:23516290

The Effect of a Combined High-Intensity Plyometric and Speed Training Program on the Running and Jumping Ability of Male Handball Players

PubMed Central

Cherif, Monsef; Said, Mohamed; Chaatani, Sana; Nejlaoui, Olfa; Gomri, Daghbaji; Abdallah, Aouidet

2012-01-01

Purpose The aim of this study was to investigate the effect of a combined program including sprint repetitions and drop jump training in the same session on male handball players. Methods Twenty-two male handball players aged more than 20 years were assigned into 2 groups: experimental group (n=11) and control group (n=11). Selection was based on variables “axis” and “lines”, goalkeepers were not included. The experimental group was subjected to 2 testing periods (test and retest) separated by 12 weeks of an additional combined plyometric and running speed training program. The control group performed the usual handball training. The testing period comprised, at the first day, a medical checking, anthropometric measurements and an incremental exercise test called yo-yo intermittent recovery test. 2 days later, participants performed the Repeated Sprint Ability test (RSA), and performed the Jumping Performance using 3 different events: Squat jump (SJ), Countermovement jump without (CMJ) and with arms (CMJA), and Drop jump (DJ). At the end of the training period, participants performed again the repeated sprint ability test, and the jumping performance. Results The conventional combined program improved the explosive force ability of handball players in CMJ (P=0.01), CMJA (P=0.01) and DJR (P=0.03). The change was 2.78, 2.42 and 2.62% respectively. No significant changes were noted in performances of the experimental group at the squat jump test and the drop jump with the left leg test. The training intervention also improved the running speed ability of the experimental group (P=0.003). No statistical differences were observed between lines or axes. Conclusion Additional combined training program between sprint repetition and vertical jump in the same training session positively influence the jumping ability and the sprint ability of handball players. PMID:22461962

The effect of a combined high-intensity plyometric and speed training program on the running and jumping ability of male handball players.

PubMed

Cherif, Monsef; Said, Mohamed; Chaatani, Sana; Nejlaoui, Olfa; Gomri, Daghbaji; Abdallah, Aouidet

2012-03-01

The aim of this study was to investigate the effect of a combined program including sprint repetitions and drop jump training in the same session on male handball players. Twenty-two male handball players aged more than 20 years were assigned into 2 groups: experimental group (n=11) and control group (n=11). Selection was based on variables "axis" and "lines", goalkeepers were not included. The experimental group was subjected to 2 testing periods (test and retest) separated by 12 weeks of an additional combined plyometric and running speed training program. The control group performed the usual handball training. The testing period comprised, at the first day, a medical checking, anthropometric measurements and an incremental exercise test called yo-yo intermittent recovery test. 2 days later, participants performed the Repeated Sprint Ability test (RSA), and performed the Jumping Performance using 3 different events: Squat jump (SJ), Countermovement jump without (CMJ) and with arms (CMJA), and Drop jump (DJ). At the end of the training period, participants performed again the repeated sprint ability test, and the jumping performance. The conventional combined program improved the explosive force ability of handball players in CMJ (P=0.01), CMJA (P=0.01) and DJR (P=0.03). The change was 2.78, 2.42 and 2.62% respectively. No significant changes were noted in performances of the experimental group at the squat jump test and the drop jump with the left leg test. The training intervention also improved the running speed ability of the experimental group (P=0.003). No statistical differences were observed between lines or axes. Additional combined training program between sprint repetition and vertical jump in the same training session positively influence the jumping ability and the sprint ability of handball players.

Biomotor structures in elite female handball players.

PubMed

Katić, Ratko; Cavala, Marijana; Srhoj, Vatromir

2007-09-01

In order to identify biomotor structures in elite female handball players, factor structures of morphological characteristics and basic motor abilities of elite female handball players (N = 53) were determined first, followed by determination of relations between the morphological-motor space factors obtained and the set of criterion variables evaluating situation motor abilities in handball. Factor analysis of 14 morphological measures produced three morphological factors, i.e. factor of absolute voluminosity (mesoendomorph), factor of longitudinal skeleton dimensionality, and factor of transverse hand dimensionality. Factor analysis of 15 motor variables yielded five basic motor dimensions, i.e. factor of agility, factor of jumping explosive strength, factor of throwing explosive strength, factor of movement frequency rate, and factor of running explosive strength (sprint). Four significant canonic correlations, i.e. linear combinations, explained the correlation between the set of eight latent variables of the morphological and basic motor space and five variables of situation motoricity. First canonic linear combination is based on the positive effect of the factors of agility/coordination on the ability of fast movement without ball. Second linear combination is based on the effect of jumping explosive strength and transverse hand dimensionality on ball manipulation, throw precision, and speed of movement with ball. Third linear combination is based on the running explosive strength determination by the speed of movement with ball, whereas fourth combination is determined by throwing and jumping explosive strength, and agility on ball pass. The results obtained were consistent with the model of selection in female handball proposed (Srhoj et al., 2006), showing the speed of movement without ball and the ability of ball manipulation to be the predominant specific abilities, as indicated by the first and second linear combination.

Bilateral Non-arteritic Anterior Ischaemic Optic Neuropathy as the Presentation of Systemic Amyloidosis.

PubMed

Kanaan, M Z; Lorenzi, A R; Thampy, N; Pandit, R; Dayan, Margaret

2017-12-01

A 75-year-old hypertensive female with stable idiopathic intermediate uveitis presented with bilateral sequential optic neuropathy with optic disc swelling. The optic neuropathy in the first affected eye (right) was thought to be due to non-arteritic anterior ischaemic optic neuropathy (NAION). Asymptomatic left optic disc swelling was found at routine review 2 months later, and a diagnosis of giant cell arteritis (GCA) was sought. Temporal artery duplex ultrasound showed the "halo sign," but a subsequent temporal artery biopsy showed light-chain (AL) amyloidosis with no signs of giant cell arteritis. In this case, bilateral sequential ischaemic optic neuropathy mimicking non-arteritic anterior ischaemic optic neuropathy was the presenting sign of systemic amyloidosis involving the temporal arteries.

Determination of thiaarenes and polycyclic aromatic hydrocarbons in workplace air of an aluminum reduction plant

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

Becker, G.; Colmsjoe, A.; Oestman, C.

1999-05-01

Quantitation of a variety of tetra-, penta-, and hexacyclic aromatic sulfur heterocycles (thiaarenes) in workplace air of an aluminum reduction plant has been made by help of gas chromatography with atomic emission detection (GC-AED). Personal exposure to those thiaarenes and to polycyclic aromatic hydrocarbons depending on work categories has been evaluated. Summarized concentrations of the thiaarenes investigated have been found to be 0.4--19.0 {micro}g/m{sup 3}. When using sulfur selective AED, samples could be analyzed without a prior separation of the thiaarenes from the PAH. The present data indicate a contribution of thiaarenes to the overall toxicity of coal tar pitchmore » volatiles in this work environment.« less

Investigation of DBS electro-oxidation reaction in the aqueous-organic solution of LiClO4.

PubMed

Darlewski, Witold; Popiel, Stanisław; Nalepa, Tomasz; Gromotowicz, Waldemar; Szewczyk, Rafał; Stankiewicz, Romuald

2010-03-15

A process of dibutyl sulphide (DBS) electro-oxidation using electrolysis and cyclic voltamperometry was investigated in water-methanol solution using different electrodes (platinum, boron doped diamond, graphite and glassy carbon). Obtained results indicate that the DBS electro-oxidation process is irreversible in voltamperometric conditions. It was shown that during DBS electrolytic oxidation on Pt, at the low anode potential (1.8 V), DBS was oxidized to sulphoxide and sulphone. Electrolysis at higher potential (up to 3.0 V) resulted in complete DBS oxidation and formation of various products, including: butyric acid, sulphuric acid, butanesulphinic acid, butanesulphonic acid, identified using gas chromatography (GC-AED) and mass spectrometry (GC-MS) methods. (c) 2009 Elsevier B.V. All rights reserved.

Improvement of Speaking Ability through Interrelated Skills

ERIC Educational Resources Information Center

Liao, Guoqiang

2009-01-01

How to improve students' ability of speaking English? That is the key point we are concerned about. This paper discusses the possibility and necessity of improving students' ability by combining the four skills of speaking, listening, reading and writing.

Effect of Mixing Ability Groups on Ability Levels Attained.

ERIC Educational Resources Information Center

de Jong, John H. A. L.

In 1983, in the Netherlands' highly differentiated school system, two types of curriculum representing different ability levels were combined as a first step towards a more heterogeneous grouping of student abilities. A study of one aspect of the results of this change compared over 1000 samples of English and German second language listening…

Independent and combined influence of the components of physical fitness on academic performance in youth.

PubMed

Esteban-Cornejo, Irene; Tejero-González, Carlos Ma; Martinez-Gomez, David; del-Campo, Juan; González-Galo, Ana; Padilla-Moledo, Carmen; Sallis, James F; Veiga, Oscar L

2014-08-01

To examine the independent and combined associations of the components of physical fitness with academic performance among youths. This cross-sectional study included a total of 2038 youths (989 girls) aged 6-18 years. Cardiorespiratory capacity was measured using the 20-m shuttle run test. Motor ability was assessed with the 4×10-m shuttle run test of speed of movement, agility, and coordination. A muscular strength z-score was computed based on handgrip strength and standing long jump distance. Academic performance was assessed through school records using 4 indicators: Mathematics, Language, an average of Mathematics and Language, and grade point average score. Cardiorespiratory capacity and motor ability were independently associated with all academic variables in youth, even after adjustment for fitness and fatness indicators (all P≤.001), whereas muscular strength was not associated with academic performance independent of the other 2 physical fitness components. In addition, the combined adverse effects of low cardiorespiratory capacity and motor ability on academic performance were observed across the risk groups (P for trend<.001). Cardiorespiratory capacity and motor ability, both independently and combined, may have a beneficial influence on academic performance in youth. Copyright © 2014 Elsevier Inc. All rights reserved.

The Consequence of Combined Pain and Stress on Work Ability in Female Laboratory Technicians: A Cross-Sectional Study.

PubMed

Jay, Kenneth; Friborg, Maria Kristine; Sjøgaard, Gisela; Jakobsen, Markus Due; Sundstrup, Emil; Brandt, Mikkel; Andersen, Lars Louis

2015-12-11

Musculoskeletal pain and stress-related disorders are leading causes of impaired work ability, sickness absences and disability pensions. However, knowledge about the combined detrimental effect of pain and stress on work ability is lacking. This study investigates the association between pain in the neck-shoulders, perceived stress, and work ability. In a cross-sectional survey at a large pharmaceutical company in Denmark 473 female laboratory technicians replied to questions about stress (Perceived Stress Scale), musculoskeletal pain intensity (scale 0-10) of the neck and shoulders, and work ability (Work Ability Index). General linear models tested the association between variables. In the multi-adjusted model, stress (p < 0.001) and pain (p < 0.001) had independent main effects on the work ability index score, and there was no significant stress by pain interaction (p = 0.32). Work ability decreased gradually with both increased stress and pain. Workers with low stress and low pain had the highest Work Ability Index score (44.6 (95% CI 43.9-45.3)) and workers with high stress and high pain had the lowest score (32.7 (95% CI 30.6-34.9)). This cross-sectional study indicates that increased stress and musculoskeletal pain are independently associated with lower work ability in female laboratory technicians.

The Fractionation of Highly Siderophile Elements (HSE) in Impact Melts and the Determination of the Meteoritic Components

NASA Astrophysics Data System (ADS)

Schmidt, G.; Palme, H.; Kratz, K. L.

1995-09-01

Lunar highland rocks contain an excess of siderophile elements, which has been attributed to meteoritic influx after the formation of the lunar crust [1-4]. Siderophile element enrichment has subsequently become a standard method for the identification of terrestrial impact craters. Janssens et al. [5], Grieve [6] and Palme et al. [7] have shown the dominant role of impact melt as the main carrier of meteoritic material at large terrestrial impact craters. This has been demonstrated at Clearwater East [8], Lappajarvi [9-11], Saaksjarvi [12], Brent [6] and Rochechouart [5]. The amount of projectile material incorporated in impact melt sheets is generally low (<1%). The highest recorded is 8% at East Clearwater, where the siderophiles are carried in a sulphide phase. In other cases, searches for siderophile anomalies at some impact structure have been largely unsuccessful. Melt bearing mixed breccias (suevitic melt) and fall-back sediments have been found to be free of meteoritic components in Brent, Lappajarvi and Ries samples [6,9,12-14]. However, from approximately 130 craters which are currently known on Earth only four clearly identified chondrites have been found as projectiles of large craters [15,16]. In this study we analyzed twenty-two impact melt samples (10 g) from Saaksjarvi (Finland), Mien and Dellen (Sweden) impact craters for Os, Re, Ir, Ru, Rh, Pd and Au by a slightly modified version of the fire assay neutron activation method using nickel sulphide as the collector [13,14]. All samples were obtained from the collection of the University of Munster. Only fresh, nearly fragment-free, fine grained samples without any sign of alteration were selected for chemical studies. All samples have been described previously [17]. The INAA procedure involved two irradiations: a short irradiation for Rh and a long irradiation for the other elements. Impact melts from Saaksjarvi are highly enriched in PGEs. The flat siderophile pattern suggests that the meteoritic component (PGE/CI = 3x10^-3 to 9x10^-3 relative to CI) in the Saaksjarvi impact melt is relatively unfractionated. Stony-iron meteorites (pallasites) as proposed earlier [7] can therefore be excluded as possible contaminants because Pd and Ir are highly fractionated in pallasites [18]. Impact melts from Mien and Dellen are moderately enriched in PGE. The concentrations are similar (PGE/CI = 3x10^-4 to 1x10^-3 relative to CI). The flat siderophile pattern of the Mien and Dellen impact samples are compatible with carbonaceous chondrite type of material, but a clear geochemical association of any of the known meteorite types is not possible because of the low signal-to-background ratio for Rh, Ru, Pd, and Au. Samples from all impact craters have low Os/PGE ratios (Os/Ir(sub)melt =0.24) compared to chondritic ratios (Os/Ir(sub)CI=1.06). It seems that the oxygen fugacity at the time of impact melting, vaporization and crystallization of the melt body may play the dominant role in the fractionation of Os and PGEs. If Os have been partially lost by volatilization of OsO4 under oxidizing conditions, then Ir is the only element to confirm meteoritic enrichments down to a level of 2x10^-4 CI chondrite. None of the other elements determined are sufficiently sensitive indicators to confirm small meteoritic enrichments, equivalent to <10^-3 CI chondrite, because of low CI/Earth crust-ratios. Acknowledgements. This work was supported by DFG. References: [1] Wasson J. T. et al. (1975) Moon, 13, 121-141. [2] Gros J. et al. (1976) Proc. LSC 7th, 2403-2425. [3] Hertogen J. et al. (1977) Proc. LSC 8th, 17-45. [4] Palme H. (1980) Proc. LPSC 11th, 481-506. [5] Janssens M.-J. et al. (1977) JGR, 82, 750-758. [6] Grieve R. A. F. (1978) Proc. LPSC 9th, 2579-2608. [7] Palme H. et al. (1980) LPSC XI, 848-850. [8] Palme H. et al. (1978) GCA, 42, 313-323. [9] Reimold W. U. and Stoffler D. (1980) Meteoritics, 14, 526-528. [10] Reimold W. U. (1980) Ph. D. thesis, Univ. of Munster, 172 pp. [11] Gobel E. et al. (1980) Z. Naturforsch., 35a, 197-203. [12] Morgan J. W. et al. (1979) GCA, 43, 803-815. [13] Schmidt G. and Pernicka E. (1991) Meteoritics, 26, 392. [14] Schmidt G. and Pernicka E. (1994) GCA, 58, 5083-5090. [15] Palme H. et al. (1981) GCA, 45, 2417-2424. [16] Grieve R. A. F. (1991) Meteoritics, 26, 174-194. [17] Maerz U. (1979) Diploma thesis, Univ. of Munster, 115 pp. [18] Davis A. M. (1977) Ph. D. thesis, Yale University, 285 pp.

Developing a Measure of General Academic Ability: An Application of Maximal Reliability and Optimal Linear Combination to High School Students' Scores

ERIC Educational Resources Information Center

Dimitrov, Dimiter M.; Raykov, Tenko; AL-Qataee, Abdullah Ali

2015-01-01

This article is concerned with developing a measure of general academic ability (GAA) for high school graduates who apply to colleges, as well as with the identification of optimal weights of the GAA indicators in a linear combination that yields a composite score with maximal reliability and maximal predictive validity, employing the framework of…

The National Football League (NFL) combine: does normalized data better predict performance in the NFL draft?

PubMed

Robbins, Daniel W

2010-11-01

The objective of this study was to investigate the predictive ability of National Football League (NFL) combine physical test data to predict draft order over the years 2005-2009. The NFL combine provides a setting in which NFL personnel can evaluate top draft prospects. The predictive ability of combine data in its raw form and when normalized in both a ratio and allometric manner was examined for 17 positions. Data from 8 combine physical performance tests were correlated with draft order to determine the direction and strength of relationship between the various combine measures and draft order. Players invited to the combine and subsequently drafted in the same year (n = 1,155) were included in the study. The primary finding was that performance in the combine physical test battery, whether normalized or not, has little association with draft success. In terms of predicting draft order from outcomes of the 8 tests making up the combine battery, normalized data provided no advantage over raw data. Of the 8 performance measures investigated, straight sprint time and jumping ability seem to hold the most weight with NFL personnel responsible for draft decisions. The NFL should consider revising the combine test battery to reflect the physical characteristics it deems important. It may be that NFL teams are more interested in attributes other than the purely physical traits reflected in the combine test battery. Players with aspirations of entering the NFL may be well advised to develop mental and technical skills in addition to developing the physical characteristics necessary to optimize performance.

Coherent beam combining in atmospheric channels using gated backscatter.

PubMed

Naeh, Itay; Katzir, Abraham

2016-02-01

This paper introduces the concept of atmospheric channels and describes a possible approach for the coherent beam combining of lasers of an optical phased array (OPA) in a turbulent atmosphere. By using the recently introduced sparse spectrum harmonic augmentation method, a comprehensive simulative investigation was performed and the exceptional properties of the atmospheric channels were numerically demonstrated. Among the interesting properties are the ability to guide light in a confined manner in a refractive channel, the ability to gather different sources to the same channel, and the ability to maintain a constant relative phase within the channel between several sources. The newly introduced guiding properties combined with a suggested method for channel probing and phase measurement by aerosol backscattered radiation allows coherence improvement of the phased array's elements and energy refocusing at the location of the channel in order to increase power in the bucket without feedback from the target. The method relies on the electronic focusing, electronic scanning, and time gating of the OPA, combined with elements of the relative phase measurements.

A gender approach to work ability and its relationship to professional and domestic work hours among nursing personnel.

PubMed

Rotenberg, Lúcia; Portela, Luciana Fernandes; Banks, Bahby; Griep, Rosane Harter; Fischer, Frida Marina; Landsbergis, Paul

2008-09-01

The association between working hours and work ability was examined in a cross-sectional study of male (N=156) and female (N=1092) nurses in three public hospitals. Working hours were considered in terms of their professional and domestic hours per week and their combined impact; total work load. Logistic regression analysis showed a significant association between total work load and inadequate work ability index (WAI) for females only. Females reported a higher proportion of inadequate WAI, fewer professional work hours but longer domestic work hours. There were no significant differences in total work load by gender. The combination of professional and domestic work hours in females seemed to best explain their lower work ability. The findings suggest that investigations into female well-being need to consider their total work load. Our male sample may have lacked sufficient power to detect a relationship between working hours and work ability.

Vendantic view on life and consciousness: BN Shanta is correct.

PubMed

Jagannadham, Medicharla Venkata

2016-01-01

The explanation for Vedanta offered by Bhakti Niskama Santa (BNS) 1 is valid from both scientific and philosophical grounds. It seems that the published critique of Gustavo Caetano-Anollés (GCA) 2 to Shanta's paper is purely emotional and does not have any valid scientific or philosophical justification. In his rebuttal to Caetano-Anollés's critique, Shanta 3 highlighted how the concept of 'Organic Whole' in Vedanta is completely different than that of Creationist Movement and Intelligent Design. Thus Caetano-Anollé's attempt to equate Vedanta with Creationist Movement and Intelligent Design is merely superfluous. This article highlights the validity of the argument made by Bhakti Niskama Shanta 1 and thus also intends to clarify why the Caetano-Anollés critique is groundless.

Four new type I restriction enzymes identified in Escherichia coli clinical isolates

PubMed Central

Kasarjian, Julie K. A.; Kodama, Yoshiaki; Iida, Masatake; Matsuda, Katsura; Ryu, Junichi

2005-01-01

Using a plasmid transformation method and the RM search computer program, four type I restriction enzymes with new recognition sites and two isoschizomers (EcoBI and Eco377I) were identified in a collection of clinical Escherichia coli isolates. These new enzymes were designated Eco394I, Eco826I, Eco851I and Eco912I. Their recognition sequences were determined to be GAC(5N)RTAAY, GCA(6N)CTGA, GTCA(6N)TGAY and CAC(5N)TGGC, respectively. A methylation sensitivity assay, using various synthetic oligonucleotides, was used to identify the adenines that prevent cleavage when methylated (underlined). These results suggest that type I enzymes are abundant in E.coli and many other bacteria, as has been inferred from bacterial genome sequencing projects. PMID:16040596

Bilateral Posterior Scleritis Associated with Giant Cell Arteritis: A Case Report.

PubMed

Erdogan, Mehmet; Sayin, Nihat; Yıldız Ekinci, Dilbade; Bayramoglu, Sadik

2017-09-15

To report a case of bilateral posterior scleritis associated with giant cell arteritis Case Report: A 62-year-old female patient presented with bilateral progressive vision loss was diagnosed with bilateral posterior scleritis. According to clinical signs and symptoms and laboratory testing, Giant cell arteritis was also diagnosed. Within 8 weeks of the corticosteroid treatment, the serous retinal detachments completely resolved and choroidal thickness decreased in both eyes. Visual acuity increased, and the symtoms related to Giant cell arteritis improved. Posterior scleritis is an inflammatory disease that may be associated with many autoimmune systemic diseases. GCA should be thought of particularly in patients over the age of 50 with bilateral involvement, and a relevant detailed history should be obtained for early and correct diagnosis and treatment.

Characterization and measurement of natural gas trace constituents. Volume 1. Arsenic. Final report, June 1989-October 1993

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

Chao, S.S.; Attari, A.

1995-01-01

The discovery of arsenic compounds, as alkylarsines, in natural gas prompted this research program to develop reliable measurement techniques needed to assess the efficiency of removal processes for these environmentally sensitive substances. These techniques include sampling, speciation, quantitation and on-line instrumental methods for monitoring the total arsenic concentration. The current program has yielded many products, including calibration standards, arsenic-specific sorbents, sensitive analytical methods and instrumentation. Four laboratory analytical methods have been developed and successfully employed for arsenic determination in natural gas. These methods use GC-AED and GC-MS instruments to speciate alkylarsines, and peroxydisulfate extraction with FIAS, special carbon sorbent withmore » XRF and an IGT developed sorbent with GFAA for total arsenic measurement.« less

Nebular and Interstellar Materials in a Giant Cluster IDP of Probable Cometary Origin

NASA Technical Reports Server (NTRS)

Messenger, S.; Brownlee, D. E.; Joswiak, D. J.; Nguyen, A. N.

2015-01-01

Comets contain a complex mixture of materials with presolar and Solar System origins. Chondritic porous interplanetary dust particles (CP-IDPs) are associated with comets by their fragile nature, unequilibrated anhydrous mineralogy and high abundances of circumstellar grains and isotopically anomalous organic materials. Comet 81P/Wild 2 samples returned by the Stardust spacecraft contain presolar materials as well as refractory 16O-rich Ca-Al-rich inclusion- (CAI), chondrule-, and AOA-like materials. We are conducting coordinated chemical, mineralogical, and isotopic studies of a giant cluster CP-IDP (U2-20-GCA) to determine the proportions of inner Solar System and interstellar materials. We previously found that this IDP contains abundant presolar silicates (approx. 1,800 ppm) and 15N-rich hotspots [6].

Targeting PRMT5 as a Novel Radiosensitization Approach for Primary and Recurrent Prostate Cancer Treatment

DTIC Science & Technology

2013-08-01

CCT G-30; KLK2 F: 50- TGG CTG TGT ACA GTC ATG GA-30; KLK2 R: 50- CCT GTG TCT TCA GGC TCA AA-30; TMPRSS2 F: 50-AGG TGC ATC CGG CTC AGT A-30; TMPRSS2 R...50-GGG TCA AGG TGA TGC ACA GT-30; PCDH11 F: 50-GCG TTT CTG ACT GTG GCT ATC-30; PCDH11 R: 50-GGA AGG GGA ATG GAA TTT TG-30; UGT2B15 F: 50-TCA AATc-Jun...GAPDH F: 50-CTG ACT TCA ACA GCG ACA CC-30; GAPDH R: 50-CCC TGT TGC TGT AGC CAA AT-30; AR F: 50- GTG GAA GCT GCA AGG TCT TC-30; AR R 50-CGA AGA CGA

The Role of the Hendra Virus and Nipah Virus Attachment Glycoproteins in Receptor Binding and Antibody Neutralization

DTIC Science & Technology

2014-01-31

portions of the NiV-sG sequence on the 5’ ends (c: 5’- CGG AAG CTG ATG AAG CAG ATC GAG GAC-3’ , d: 5’-CTG GTG TAC TT CTT GAT CCT GGC CAG-3’). The leader...template-pcDNA-GCN(tet)-HeV-sG, forward primer: 5’- GTG GAG ATC TAC AAC ACC GGC GAC TC-3’ and reverse primer: 5’- GAG TCG CCG GTG TTG TAG ATC TCC AC-3...CCC CGC TCC GTG GCA ATA TTA CTA CTA C YA YAAHPS GAG CAG TAC GCC GCC CAT CCG TCC C F/L/W FAPHLW G TTC GCC CCC CAT CTG TGG CAA TAT TAC TAC TAC

Vendantic view on life and consciousness: BN Shanta is correct

PubMed Central

Jagannadham, Medicharla Venkata

2016-01-01

ABSTRACT The explanation for Vedanta offered by Bhakti Niskama Santa (BNS)1 is valid from both scientific and philosophical grounds. It seems that the published critique of Gustavo Caetano-Anollés (GCA)2 to Shanta's paper is purely emotional and does not have any valid scientific or philosophical justification. In his rebuttal to Caetano-Anollés's critique, Shanta3 highlighted how the concept of ‘Organic Whole’ in Vedanta is completely different than that of Creationist Movement and Intelligent Design. Thus Caetano-Anollé's attempt to equate Vedanta with Creationist Movement and Intelligent Design is merely superfluous. This article highlights the validity of the argument made by Bhakti Niskama Shanta1 and thus also intends to clarify why the Caetano-Anollés critique is groundless. PMID:27829974

Angrites: A Volatile-rich Variety of Asteroidal Basalt (Except for Alkalis and Gallium!)

NASA Astrophysics Data System (ADS)

Warren, P. H.; Kallemeyn, G. W.

1995-09-01

Angrites are commonly viewed as extremely volatile-depleted, and a related notion is that they formed by differentiation of a very CAI-rich material [e.g., 1]. Partial melting experiments reportedly reproduce the bulk compositions (although not fassaite-rich mineralogy) of angrites with Allende as starting material [2], but highly CAI-rich parent materials are difficult to reconcile with isotopic and REE data [3,4]. Mittlefehldt and Lindstrom [5] inferred from the low Na/Al ratios of angrites that outgassing, and thus primordial magmatism, was more intense on their parent body than on the eucrite parent asteroid. Of seven elements that (a) have been adequately determined in angrites, and (b) are far more volatile (solar-nebula 50% condensation T [6] = 690-430 K) than the alkalis (1000-910 K), four are enriched, and none is significantly depleted, in average angrite compared to average eucrite or low-Ti mare basalt (Figure). Gallium, which is of intermediate volatility (830 K), is depleted to roughly the same extent as Na and K. Results for A881371 [3] are incomplete (Zn, 6 micrograms/g, is near INAA detection limit), but even based only on AdoR and the two LEW angrites, this pattern seems firmly established. Apparent gas cavities in A881371 [7] also suggest that volatiles are far from uniformly depleted. The only elements known to be depleted, as volatiles, by clearly significant factors in angrites versus eucrites or lunar basalts, are alkalis plus gallium. Besides being moderately volatile, a noteworthy characteristic shared among Ga and alkalis (and not shared with elements such as Br, Se, and Zn) is that these elements probably tend to partition into crustal feldspar during gross differentiation of small (low-pressure) bodies. If gallium + alkalis were depleted by a single process starting from "normal" chondritic material, that process would seem to require selective exposure of a feldspar-enriched region (i.e., crust) to extremely high temperature. Igneous crystallization of the angrites occurred when the solar system was still extremely young, and apparently <=2 Ma after the volatile-depletion process [4]. The data of [4] eliminate 26Al as a potential heat source for magmatism. The angrite volatile pattern may be the product of heating by an intense, short-lived heat source that melted and partially vaporized the crust of an asteroid(s) (not necessarily the final angrite asteroid), without much affecting the deep interior(s), which later (through mixing and/or magmatism) replenished the angritic materials in most volatiles, but not alkalis and Ga. Exogenic heating, as in the often-conjectured (but hard to test) hypothesis that a major early heat source was enhanced solar luminosity (as in FU-Orionis cycles), would seem to be required. LEW 87051 and A881371 are rich in compositionally diverse olivine xenocrysts, and A881371 contains a possible FeS xenocryst [7]. These, and the angrites' great siderophile diversity [3], tend to suggest that magmatism and intensely disruptive cratering (with mixing of precursor materials) were contemporaneous. This scenario is admittedly speculative, but the volatile-depletion pattern is difficult to rationalize with any other model. References: [1] Prinz M. and Weisberg M. (1995) Antarct. Meteorites, XX, 207-210. [2] Jurewicz A. et al. (1993) GCA, 57, 2123-2139. [3] Warren P. et al. (1995) Antarct. Meteorites, XX, 261-264. [4] Lugmair G. and Galer S. 1992) GCA, 56, 1673-1694. [5] Mittlefehldt D. and Lindstrom M. (1990) GCA, 54, 3209-3218. [6] Wasson J. (1985) Meteorites. [7] Warren P. and Davis A. (1995) Antarct. Meteorites, XX, 257-260.

Helium Diffusion in Olivine

NASA Astrophysics Data System (ADS)

Cherniak, D. J.; Watson, E. B.

2011-12-01

Diffusion of helium has been characterized in natural Fe-bearing olivine (~Fo90) and synthetic forsterite. Polished, oriented slabs of olivine were implanted with 3He, at 100 keV at a dose of 5x1015/cm2 or at 3.0 MeV at a dose of 1x1016/cm2. A set of experiments on the implanted olivine were run in 1-atm furnaces. In addition to the one-atm experiments, experiments on implanted samples were also run at higher pressures (2.6 and 2.7 GPa) to assess the potential effects of pressure on He diffusion and the applicability of the measured diffusivities in describing He transport in the mantle. The high-pressure experiments were conducted in a piston-cylinder apparatus using an "ultra-soft" pressure cell, with the diffusion sample directly surrounded by AgCl. 3He distributions following experiments were measured with Nuclear Reaction Analysis using the reaction 3He(d,p)4He. This direct profiling method permits us to evaluate anisotropy of diffusion, which cannot be easily assessed using bulk-release methods. For diffusion in forsterite parallel to c we obtain the following Arrhenius relation over the temperatures 250-950°C: D = 3.91x10-6exp(-159 ± 4 kJ mol-1/RT) m2/sec. The data define a single Arrhenius line spanning more than 7 orders of magnitude in D and 700°C in temperature. Diffusion parallel to a appears slightly slower, yielding an activation energy for diffusion of 135 kJ/mol and a pre-exponential factor of 3.73x10-8 m2/sec. Diffusion parallel to b is slower than diffusion parallel to a (by about two-thirds of a log unit); for this orientation an activation energy of 138 kJ/mol and a pre-exponential factor of 1.34x10-8 m2/sec are obtained. This anisotropy is broadly consistent with observations for diffusion of Ni and Fe-Mg in olivine. Diffusion in Fe-bearing olivine (transport parallel to b) agrees within uncertainty with findings for He diffusion in forsterite. The higher-pressure experiments yield diffusivities in agreement with those from the 1-atm experiments, indicating that the results reported here can be reasonably applied to modeling He transport in the upper mantle. The insensitivity of He diffusion to pressure over the investigated range of conditions suggests that compression of the mineral lattice is not sufficient to significantly influence migration of the relatively small helium atoms, which likely diffuse via crystal interstices. The He diffusivities in this work are generally consistent with results from the study of Futagami et al. (1993), who measured He diffusion in natural olivine by outgassing 4He implanted samples, and with the diffusivities measured by bulk-release of 4He and 3He by Shuster et al. (2003), but are about 2 orders of magnitude slower than the recent findings of Tolstikhin et al. (2010) and Blard et al. (2008) . An up-temperature extrapolation of our data also show reasonable agreement with the higher-temperature measurements of Hart (1984). Blard et al. (2008) GCA 72, 3788-3803; Futagami et al. (1993) GCA 57, 3177-3194; Hart (1984) EPSL 70, 297-302; Shuster et al.( 2003) EPSL 217, 19-32; Tolstikhin et al. (2010) GCA 74, 1436-1447

Experimental Partitioning of As and SB Among Metal, Troilite, Schreibersite, Barringerite, and Metallic Liquid

NASA Astrophysics Data System (ADS)

Jones, J. H.; Casanova, I.

1993-07-01

We have performed a series of experiments to evaluate the behaviors of As and Sb in metallic systems. Because of the reputed chalcophile nature of these elements, we wrongly anticipated that they would follow S and that, compared to the Fe-X systems [1], (solid metal/liquid metal) partition coefficients would be considerably lower in S-bearing systems. Experimental and Analytical: Experiments were performed in sealed silica tubes as in [2]. Starting materials were high-purity metals, natural pyrite, and natural stibnite. Charges were doped either with As or Sb. Experiments were held at either 950 degrees C for six days or 1250 degrees C for three days. Typical experimental assemblages consisted either of taenite and coexisting Fe-Ni-S-X liquid (1250 degrees and 950 degrees C) or an assemblage of troilite, schreibersite, and Fe-Ni-S-P-X liquid (950 degrees C). The schreibersite-bearing, As-doped charge also contained barringerite (Fe,Ni)2P. Charges were mounted in epoxy, polished, and analyzed using a Cameca SX-50 electron microprobe and standard techniques. Results: Phases appeared homogeneous. Our results, along with partition coefficients inferred for the S-free system, are given in Table 1. Table 1 appears here in the hard copy. Discussion: Our results indicate that As behaves as a siderophile element at low temperatures, very analogous to Au. While the siderophility of Sb increases with decreasing temperature, it remains incompatible in solid metal. In this regard Sb is unique. Both As and Sb are very incompatible in troilite. Arsenic is weakly incompatible in schreibersite and strongly compatible in barringerite. Nickel shows no preference for either phosphide. Nickel partition coefficients for metal and schreibersite are similar to those measured previously [3]. On a lnD vs. ln(1-2 alpha X(S)) diagram [4], the data for Sb and As subparallel each other, indicating similar dependencies on S, despite their very different partition coefficients. Arsenic behaves similarly to P. The As and Sb partition coefficients for the S-free system, inferred for kamacite (alpha-iron) from the Fe-As and Fe-Sb phase diagrams [1], are probably not applicable to taenite (gamma-iron). Extrapolation of our data to zero S indicates that the taenite partition coefficients for As and Sb are likely to be much lower than for kamacite. In discussing the fractional crystallization of iron meteorites, Scott [5] originally grouped Au, As, Sb, and Co and assigned them a (solid metal/liquid metal) partition coefficient of about 0.4. This distinguished them from P, which was given a partition coefficient of 0.2. Given the strong decoupling of As and Sb in our experiments, the general coherence of As and Sb in iron meteorites [5] is surprising. To explore this further, we have derived a new equation for the slopes of LogEl vs. LogNi diagrams, which takes into account changes in D. References: [1] Moffatt W. G. (1986) Handbook of Binary Phase Diagrams, Genium. [2] Jones J. H. and Drake M. J. (1983) GCA, 47, 1199. [3] Jones J. H. et al. (1993) GCA, 57, 453-460. [4] Jones J. H. and Malvin D. J. (1990) Metall. Trans., 21B, 697-706. [5] Scott E. R. D. (1972) GCA, 36, 1205.

Reaction paths and host phases of uranium isotopes (235U; 238U), Saanich Inlet

NASA Astrophysics Data System (ADS)

Amini, M.; Holmden, C. E.; Francois, R. H.

2009-12-01

In recent times, Uranium has become increasingly the focus of stable isotope fractionation studies. Variations in 238U/235U have been reported as a result of redox reactions [1,2] from the nuclear field shift effect [3], and a mass-dependent, microbially-mediated, kinetic isotope effect [4]. The 238U/235U variability caused by changes in environmental redox conditions leads to an increase in the 238U/235U ratios of the reduced U species sequestered into marine sediments. This points to U isotope variability as a new tool to study ancient ocean redox changes. However, the process by which reduced sediments become enriched in the heavy isotopes of U is not yet known, and hence the utility of 238U/235U as a redox tracer remains to be demonstrated. In order to further constrain sedimentary U enrichment and related isotope effect, we are investigating U isotopic compositions of water samples and fresh surface sediment grab samples over a range of redox conditions in the seasonally anoxic Saanich Inlet, on the east coast of Vancouver Island. U was sequentially extracted from sediments in order to characterize specific fractions for their isotopic composition. The measurements were carried out by MC-ICPMS using 233U/236U-double spike technique. The data are reported as δ238U relative to NBL 112a with a 238U/235U ratio of 137.88 (2sd). External precision is better than 0.10‰ (2sd). Fifteeen analyses of seawater yielded δ238U of -0.42±0.08‰ (2sd). The results for the water samples indicate a homogenous δ238U value throughout the Saanich Inlet water column that matches the global seawater signature. All of the water samples from above and below average -0.42±0.05‰ (2sd). In contrast, a plankton net sample yielded a distinctly different, (about 0.5‰ lighter) isotope value. Bacterial reduction experiments [4] have also shown isotope enrichment factors of about -0.3‰. In addition, metal isotope fractionation occurs during adsorption with the light isotope being preferentially adsorbed [5]. Whether plankton mediated chemical reduction or scavenging causes this fractionation will be further investigated by leaching experiments on sediment trap samples. By contrast, weak acidic leachates (at pH 6) of suboxic bottom sediments, tend towards higher δ238U values. For oxic sediments, U contents of this fraction were below detection limit. Stronger leaching at pH 3 removed most of the uranium from suboxic and oxic sediments. For oxic sediments, this fraction yields the seawater δ238U signature, while the U released from the suboxic sample is about 0.2‰ heavier. This matches the value for previously reported bulk analyses of suboxic sediments [1] implying that the reduced sedimentary U is released by this treatment,. Major and trace element analyses and XRD patterns will help relating this fraction to a specific mineral or reactive phase. [1] Weyer et al. (2007) GCA 72, 345-399. [2] Stirling et al. (2007) EPSL 264, 208-225. [3] Schauble (2007) GCA 71, 2170-2189. [4] Rademacher et al. (2006) Environ. Sci. Technol. 40,6943-6948. [5] Wasylenki (2009) GCA A1419.

CR chondrites: Shock, aqueous alteration and terrestrial weathering

NASA Astrophysics Data System (ADS)

Abreu, N. M.

2012-12-01

CR chondrite are a group asteroidal meteorites, whose importance lies in the exotic organic and presolar material [1] found in its most pristine members and in the broad range of alteration features represented in the remaining specimens in this group [2]. This FE-SEM, EMPA, FIB/TEM study takes advantage of the CR's mineralogical diversity to define different trends of secondary alteration, by comparing the CR3s to the Antarctic CRs: MIL 07525, MIL 07513, GRA 06100, LAP 04516, GRO 03116, GRO 95577, and EET 96259. Collisions and subsequent annealing have affected MIL 07513, GRA 06100, and GRO 03116. Shock stages are often assigned based on progressive changes in the textures of olivines and feldspars. However, the large olivines in shocked CRs do not appear to record these process. Opaques, on the other hand, preserve hallmark signatures of impacts, such as crystalline metal/sulfide veins. Opaque nodules in MIL 07513, GRA 06100, GRO 03116 consist of intergrowths of μm-sub μm FeNi-rich metal, kamacite, Fe-sulfides, Fe-oxides, nm-sized metallic Cu and CuFe (~85 wt.% Cu, 14 wt.% Fe ± < 1wt.% Co, Ni, S) alloys. MIL 07525, GRO 03116, EET 96259, LAP 04516, and GRO 95577 show increasing signs of aqueous alteration, such as increasing amounts of ordered phyllosilicates. Although most phyllosilicates are intergrowths of Fe-rich serpentine and saponite, LAP 04516 also contains large (μm-sized), interpenetrating, Fe-rich (cronstedtite-like) phyllosilicates packages with 14Å basal spacings, similar to those observed in CI chondrites by [3]. Heterogeneously interspersed within phyllosilicates are amorphous Fe-rich silicates and small grains (<50nm) of Fe-rich sulfides, partly oxidized sulfides, and in LAP 04516, tochilinite. Tochilinite shows consistent enrichments in Si (~5 wt.%), suggesting that this meteorite has undergone similar pathways of aqueous alteration as CM chondrites [e.g., 4-5]. Despite the myriad of mineralogical changes triggered by secondary and tertiary process affecting the CRs, the relationship between the average S and Fe contents of matrices are good indicators of the alteration histories of these chondrites. The average S versus Fe contents of CR matrices follow a roughly linear trend. The most aqueously altered CRs (e.g., LAP 04516) have the lowest Fe and the highest S content. The matrices in shocked CRs, MIL 07513, GRA 06100, GRO 03116, have the lowest S content of the studied CRs. They are also the most Fe-rich. The CR3 chondrites fall somewhere in the middle of the S vs. Fe plot. Terrestrial weathering creates some scattering due to its contribution to the Fe-content of the matrix. If the precursor materials of the shocked CRs composi-tionally resemble CR3 chondrites, low S content of shocked CR matrices probably resulted from volatile losses driven by shock and annealing. Whereas increasing Fe-contents are probably linked to impact-driven hydrothermal mobilization of Fe from kamacite nodules. References: [1] Floss et al. 2009. Ap. J. 697: 1242-1255. [2] Abreu N. M. 2007. [3] Tomeoka K. & Buseck P. R. 1988. GCA 52: 1627-1640. [4] Tomeoka K. & Buseck P. R. 1985. GCA 49: 21-49-2163. [5] Rubin A. et al. 2007. GCA 71: 2361-2382. Acknowledgements: Funded by NNX11AH10G grant and conducted at Penn State and ARES-JSC. Meteorite kindly pro-vided by the JSC Antarctic meteorite curators.

Intervention and follow-up on human esophageal precancerous lesions in Henan, northern China, a high-incidence area for esophageal cancer.

PubMed

Wang, Li Dong; Zhou, Qi; Feng, Chang Wei; Liu, Bin; Qi, Yi Jun; Zhang, Yan Run; Gao, Shan Shan; Fan, Zong Min; Zhou, Yun; Yang, Chang S; Wei, Jun Ping; Zheng, Shu

2002-02-01

Esophageal cancer (EC) remains a leading cause of cancer-related deaths in Linzhou (formerly Linxian) and Huixian of Henan province, northern China, which has been well recognized as the highest incidence area for EC. The lack of useful chemoprevention agents and early detection methods is the key factors for stable EC incidence in these areas. Human esophageal carcinogensis has been considered as a multistep progressive process. The natural history for EC, however is not very clear. Follow-up studies with linear repeated biopsies and histopathological examination were performed on 778 subjects from Linzhou and Huixian. Of these subjects, 578 subjects were followed for 11 years (1989-2000), 400 subjects with different severity of esophageal precancerous lesions were randomly divided into 2 groups for intervention studies with calcium and decaffeinated green tea (DGT). Each group included 200 subjects (100 subjects for treatment, and 100 subjects for placebo). In calcium group, each subject received an oral supplementation of 1,200 mg of calcium daily for 11 months. In DGT group, each subject received 5 mg of DGT daily for 12 months. In placebo group, each subject received placebo pill for 11 months (calcium group) and 12 month (DGT group). At the entry and the end of the trial, esophageal biopsy specimens were taken at the middle and the lower thirds of the esophagus and from macroscopic lesions, if only, of each subject. DGT trail did not show apparent difference between the treatment and placebo group in alleviating the esophageal precancerous lesions and abnormal cell proliferation. For the calcium intervention study, after 11 years' follow-up, 10 subjects had developed into cancers in the calcium group (10%, 8 EC and 2 GCA), and 8 subjects developed into EC in the placebo group (8%). All these patients were diagnosed at very early stage of cancer (symptom-free). Of the 578 subjects, 25 (18 males and 7 females) had developed into EC (n = 23, 4.3%) and gastric cardia cancer (GCA, n = 2, 0.3%), during the 11 years' follow-up. The mean time of cancer development (from entry of the follow-up study to the cancer detection) was 5.0 +/- 2.9 years (males) and 4.7 +/- 3.2 years (females). Of the 25 patients with EC and GCA, 11 were from the 387 followed subjects with "normal" histomorphology of biopsy at the entry of the follow-up study (3%, 11/387), 2 were from the subjects with basal cell hyperplasia, grade I (BCH I, 2%, 2/94), 7 from the subjects with BCH grade II (BCH II, 10%, 7/72), and 5 from BCH III and dysplasia (20%, 5/25). DGT trail was not shown to have beneficial effects in alleviating esophageal precancerous lesions and abnormal cell proliferation patterns. Calcium supplementation did not produce apparent long-term effects on EC. BCH II could be considered as precancerous lesions of EC. The quantitative histopathological analysis in terms of number of proliferating basal cell layers is of importance in determining the high-risk subjects for EC and evaluating the intervention results. Follow-up studies with repeated endoscopic biopsies are the powerful strategy for early detection and mortality control of EC and GAC in the high incidence area.

Estimation of diversity and combining abilities in Helianthus annuus L. under water stress and normal conditions.

PubMed

Saba, M; Khan, F A; Sadaqat, H A; Rana, I A

2016-10-24

Sunflower cannot produce high yields under water-limiting conditions. The aim of the present study was to prevent the impediments on yield and to develop varieties with high-yield potential under water scarce conditions. For achieving this objective, it is necessary to detect parents with desirable traits that mainly depend on the action of genes controlling the trait under improvement, combining ability, and genetic makeup of the parents. Heterosis can also be used to pool the desirable genes from genetically divergent varieties and these divergent parents could be detected by molecular studies. Ten tolerant and five susceptible tester lines were selected, crossed, and tested for genetic diversity using simple sequence repeat primers. We identified two parents (A-10.8 and G-60) that showed maximum (46.7%) genetic dissimilarity. On an average 3.1 alleles per locus were detected for twenty pair of primers. Evaluation of mean values revealed that under stress conditions the mean performances of the genotypes were reduced for all traits under study. Parent A-10.8 was consistent as a good general combiner for achene yield per plant under both non-stress and stress conditions. Line A-10.8 in the hybrid A-10.8 x G-60 proved to be a good combiner as it showed negative specific combining ability (SCA) effects for plant height and internodal length and positive SCA effects for head weight, achene yield per plant, and membrane stability index. Valuable information on gene action, combining ability, and heterosis was generated, which could be used in further breeding programs.

Building and Retaining the Career Force: New Procedures for Accessing and Assigning Army Enlisted Personnel: Annual Report 1990 Fiscal Year

DTIC Science & Technology

1992-05-01

researched, valid measure of general cognitive abilities. However, many critical Army tasks appear to require psychomotor and perceptual skills for their...temperament (achievement, discipline, stress toler- ance), psychomotor ability (e.g., eye-hand coordination), and spatial ability to job performance...answered: (1) What combinations of aptitude, temperament, psychomotor ability, and spatial ability, measured at or before entry into the Army, best

Usefulness of combining gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for diagnosing the macroscopic classification of small hepatocellular carcinoma.

PubMed

Kobayashi, Tomoki; Aikata, Hiroshi; Hatooka, Masahiro; Morio, Kei; Morio, Reona; Kan, Hiromi; Fujino, Hatsue; Fukuhara, Takayuki; Masaki, Keiichi; Ohno, Atsushi; Naeshiro, Noriaki; Nakahara, Takashi; Honda, Yohji; Murakami, Eisuke; Kawaoka, Tomokazu; Tsuge, Masataka; Hiramatsu, Akira; Imamura, Michio; Kawakami, Yoshiiku; Hyogo, Hideyuki; Takahashi, Shoichi; Chayama, Kazuaki

2015-11-01

Non-simple nodules in hepatocellular carcinoma (HCC) correlate with poor prognosis. Therefore, we examined the diagnostic ability of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) and contrast-enhanced ultrasound (CEUS) for diagnosing the macroscopic classification of small HCCs. A total of 85 surgically resected nodules (≤30 mm) were analyzed. HCCs were pathologically classified as simple nodular (SN) and non-SN. By evaluating hepatobiliary phase (HBP) of EOB-MRI and Kupffer phase of CEUS, the diagnostic abilities of both modalities to correctly distinguish between SN and non-SN were compared. Forty-six nodules were diagnosed as SN and the remaining 39 nodules as non-SN. The area under the ROC curve (AUROCs, 95% confidence interval) for the diagnosis of non-SN were EOB-MRI, 0.786 (0.682-0.890): CEUS, 0.784 (0.679-0.889), in combination, 0.876 (0.792-0.959). The sensitivity, specificity, and accuracy were 64.1%, 95.7%, and 81.2% in EOB-MRI, 56.4%, 97.8%, and 78.8% in CEUS, and 84.6%, 95.7%, and 90.6% in combination, respectively. High diagnostic ability was obtained when diagnosed in both modalities combined. The sensitivity was especially statistically significant compared to CEUS. Combined diagnosis by EOB-MRI and CEUS can provide high-quality imaging assessment for determining non-SN in small HCCs. • Non-SN has a higher frequency of MVI and intrahepatic metastasis than SN. • Macroscopic classification is useful to choose the treatment strategy for small HCCs. • Diagnostic ability for macroscopic findings of EOB-MRI and CEUS were statistically equal. • The diagnosis of macroscopic findings by individual modality has limitations. • Combined diagnosis of EOB-MRI and CEUS provides high diagnostic ability.

An Analysis of Content Knowledge and Cognitive Abilities as Factors That Are Associated with Algebra Performance

ERIC Educational Resources Information Center

McLean, Tamika Ann

2017-01-01

The current study investigated college students' content knowledge and cognitive abilities as factors associated with their algebra performance, and examined how combinations of content knowledge and cognitive abilities related to their algebra performance. Specifically, the investigation examined the content knowledge factors of computational…

A New Chicken Genome Assembly Provides Insight into Avian Genome Structure.

PubMed

Warren, Wesley C; Hillier, LaDeana W; Tomlinson, Chad; Minx, Patrick; Kremitzki, Milinn; Graves, Tina; Markovic, Chris; Bouk, Nathan; Pruitt, Kim D; Thibaud-Nissen, Francoise; Schneider, Valerie; Mansour, Tamer A; Brown, C Titus; Zimin, Aleksey; Hawken, Rachel; Abrahamsen, Mitch; Pyrkosz, Alexis B; Morisson, Mireille; Fillon, Valerie; Vignal, Alain; Chow, William; Howe, Kerstin; Fulton, Janet E; Miller, Marcia M; Lovell, Peter; Mello, Claudio V; Wirthlin, Morgan; Mason, Andrew S; Kuo, Richard; Burt, David W; Dodgson, Jerry B; Cheng, Hans H

2017-01-05

The importance of the Gallus gallus (chicken) as a model organism and agricultural animal merits a continuation of sequence assembly improvement efforts. We present a new version of the chicken genome assembly (Gallus_gallus-5.0; GCA_000002315.3), built from combined long single molecule sequencing technology, finished BACs, and improved physical maps. In overall assembled bases, we see a gain of 183 Mb, including 16.4 Mb in placed chromosomes with a corresponding gain in the percentage of intact repeat elements characterized. Of the 1.21 Gb genome, we include three previously missing autosomes, GGA30, 31, and 33, and improve sequence contig length 10-fold over the previous Gallus_gallus-4.0. Despite the significant base representation improvements made, 138 Mb of sequence is not yet located to chromosomes. When annotated for gene content, Gallus_gallus-5.0 shows an increase of 4679 annotated genes (2768 noncoding and 1911 protein-coding) over those in Gallus_gallus-4.0. We also revisited the question of what genes are missing in the avian lineage, as assessed by the highest quality avian genome assembly to date, and found that a large fraction of the original set of missing genes are still absent in sequenced bird species. Finally, our new data support a detailed map of MHC-B, encompassing two segments: one with a highly stable gene copy number and another in which the gene copy number is highly variable. The chicken model has been a critical resource for many other fields of study, and this new reference assembly will substantially further these efforts. Copyright © 2017 Warren et al.

Evaluation of self-reported work ability and usefulness of interventions among sick-listed patients.

PubMed

Wåhlin, Charlotte; Ekberg, Kerstin; Persson, Jan; Bernfort, Lars; Öberg, Birgitta

2013-03-01

To describe the types of intervention offered, to investigate the relationship between the type of intervention given, patient-reported usefulness of interventions and the effect on self-reported work ability in a cohort of sick-listed patients with musculoskeletal disorders (MSD) or mental disorders (MD). A prospective cohort study was performed including 810 newly sick-listed patients (MSD 62 % and MD 38 %). The baseline questionnaire included sociodemographic characteristics and measures of work ability. The 3-month follow-up questionnaire included measures of work ability, type of intervention received, and judgment of usefulness. Twenty-five percent received medical intervention modalities (MI) only, 45 % received a combination of medical and rehabilitative intervention modalities (CRI) and 31 % received work-related interventions combined with medical or rehabilitative intervention modalities (WI). Behavioural treatments were more common for patients with MD compared with MSD and exercise therapy were more common for patients with MSD. The most prevalent workplace interventions were adjustment of work tasks or the work environment. Among patients with MD, WI was found to be useful and improved work ability significantly more compared with only MI or CRI. For patients with MSD, no significant differences in improved work ability were found between interventions. Patients with MD who received a combination of work-related and clinical interventions reported best usefulness and best improvement in work ability. There was no difference in improvements in work ability between rehabilitation methods in the MSD group. There seems to be a gap between scientific evidence and praxis behaviour in the rehabilitation process. Unimodal rehabilitation was widely applied in the early rehabilitation process, a multimodal treatment approach was rare and only one-third received work-related interventions. It remains a challenge to understand who needs what type of intervention.

Combination of rapamycin and garlic-derived S-allylmercaptocysteine induces colon cancer cell apoptosis and suppresses tumor growth in xenograft nude mice through autophagy/p62/Nrf2 pathway.

PubMed

Li, Siying; Yang, Guang; Zhu, Xiaosong; Cheng, Lin; Sun, Yueyue; Zhao, Zhongxi

2017-09-01

The natural plant-derived product S-allylmercapto-cysteine (SAMC) has been studied in cancer therapy as a single and combination chemotherapeutic agent. The present study was employed to verify the combination use of SAMC and rapamycin that is the mTOR inhibitor with anticancer ability but has limited efficacy due to drug resistance, and to explore the underlying mechanisms. We combined rapamycin and SAMC for colorectal cancer treatment in the HCT‑116 cancer cells and a xenograft murine model. The in vivo study was established by xenografting HCT‑116 cells in BALB/c nude mice. It was found that the combination therapy had enhanced tumor-suppressing ability with the upregulation of the Bax/Bcl-2 ratio as a consequence of activated apoptosis, inhibition of autophagic activity and prevention of Akt phosphorylation. The rapamycin and SAMC combination activated antioxidant transcription expressions of Nrf2 and downstream gene NQO1. Concomitantly, autophagosome cargo p62 was downregulated, indicating that the p62 played a negative-regulatory role between Nrf2 and autophagy. Our results show that the combination of SAMC and rapamycin enhanced the anticancer ability, which could be used for the treatment of colorectal cancer. The underling mechanism of autophagy/p62/Nrf2 pathway discovered may provide a new direction for drug development, especially for traditional Chinese medicines.

Surfactant biocatalyst for remediation of recalcitrant organics and heavy metals

DOEpatents

Brigmon, Robin L [North Augusta, SC; Story, Sandra [Greenville, SC; Altman, Denis J [Evans, GA; Berry, Christopher J [Aiken, SC

2011-03-15

Novel strains of isolated and purified bacteria have been identified which have the ability to degrade petroleum hydrocarbons including a variety of PAHs. Several isolates also exhibit the ability to produce a biosurfactant. The combination of the biosurfactant-producing ability along with the ability to degrade PAHs enhances the efficiency with which PAHs may be degraded. Additionally, the biosurfactant also provides an additional ability to bind heavy metal ions for removal from a soil or aquatic environment.

Surfactant biocatalyst for remediation of recalcitrant organics and heavy metals

DOEpatents

Brigmon, Robin L [North Augusta, SC; Story, Sandra [Greenville, SC; Altman, Denis [Evans, GA; Berry, Christopher J [Aiken, SC

2009-01-06

Novel strains of isolated and purified bacteria have been identified which have the ability to degrade petroleum hydrocarbons including a variety of PAHs. Several isolates also exhibit the ability to produce a biosurfactant. The combination of the biosurfactant-producing ability along with the ability to degrade PAHs enhances the efficiency with which PAHs may be degraded. Additionally, the biosurfactant also provides an additional ability to bind heavy metal ions for removal from a soil or aquatic environment.

Surfactant biocatalyst for remediation of recalcitrant organics and heavy metals

DOEpatents

Brigmon, Robin L [North Augusta, SC; Story, Sandra [Greenville, SC; Altman, Denis J [Evans, GA; Berry, Christopher J [Aiken, SC

2011-05-03

Novel strains of isolated and purified bacteria have been identified which have the ability to degrade petroleum hydrocarbons including a variety of PAHs. Several isolates also exhibit the ability to produce a biosurfactant. The combination of the biosurfactant-producing ability along with the ability to degrade PAHs enhances the efficiency with which PAHs may be degraded. Additionally, the biosurfactant also provides an additional ability to bind heavy metal ions for removal from a soil or aquatic environment.

Surfactant biocatalyst for remediation of recalcitrant organics and heavy metals

DOEpatents

Brigmon, Robin L [North Augusta, SC; Story, Sandra [Greenville, SC; Altman,; Denis, J [Evans, GA; Berry, Christopher J [Aiken, SC

2011-03-29

Novel strains of isolated and purified bacteria have been identified which have the ability to degrade petroleum hydrocarbons including a variety of PAHs. Several isolates also exhibit the ability to produce a biosurfactant. The combination of the biosurfactant-producing ability along with the ability to degrade PAHs enhances the efficiency with which PAHs may be degraded. Additionally, the biosurfactant also provides an additional ability to bind heavy metal ions for removal from a soil or aquatic environment.

Feasibility of Iodine and Bromine analysis in Genesis AloS collectors

NASA Astrophysics Data System (ADS)

Pravdivtseva, O.; Meshik, A.; Hohenberg, C. M.; Burnett, D. S.

2011-12-01

Comparison of solar, meteoritic and terrestrial elemental abundances provides understanding of the formation and evolution of the solar system. Yet, the majority of the solar abundances are based on meteoritic values [1-6]. As a continuation of our noble gas measurements of the Solar Wind (SW) [7] we attempted to evaluate the possibility of SW-iodine and SW-bromine analyses in the Genesis Solar Wind Aluminum on Sapphire collectors (AloS) using the conversions: 127I(n,γβ)128Xe, 79Br(n,γβ)80Kr and 81Br(n,γβ)82Kr. To estimate the extent of terrestrial halogen contamination in Genesis collectors, several flown fragments of AloS were submerged in methanol (for 1 hour and for 48 hours), rinsed, dried, sealed under vacuum in fused quartz ampoules and irradiated at the Missouri University Research Reactor receiving fluence ˜ 2E+19 thermal neutrons/cm2. Single step laser extraction using 1064 nm laser ablation of 0.7 cm2 area demonstrated clear signature of solar wind as indicated by 129Xe/132Xe = 1.045 ± 0.005, while 128Xe/132Xe = 1.01 ± 0.03 had a 12-fold excess compared to the solar value. Longer washing apparently reduces iodine contamination 4 times, implying that it is surface correlated. Krypton analysis showed 17% excess in 82Kr and 3-fold excess in 80Kr in agreement with their production ratio. A longer 48-hour washing reduced Br contamination 50 times. In order to better separate SW halogens from ubiquitous terrestrial contamination we employed a depth-profiling of AloS using 266 nm laser ablation. Laser beam power was increased in 12 consecutive steps using a combination of controlled defocusing and attenuation by a polarizing beamsplitter. Depth profile analysis revealed that terrestrial halogen contamination is present at the surface and at the interface between Al and sapphire substrate and is more pronounced for iodine, as indicated by 128Xe/132Xe ratio that is higher than atmospheric and solar wind values in all 12 rasters. While washing procedure reduced surface contamination, it did not affect iodine and bromine associated with the interface. Thus, cleaner Si-based Genesis collectors could be more suitable for SW halogen analyses. Our first results suggest that determination of solar iodine and bromine is potentially feasible, considering the possibility of analyzing larger collector areas irradiated with higher neutron fluence in order to improve counting statistics of the measurements. Supported by NASA grant NNX07AM76G. [1] Anders E. and Ebihara M. 1982. GCA 46:2363-2380. [2] Anders E. and Grevesse N. 1989. GCA 53:197-214. [3] Cameron A. G. W. 1968. in Origin and distribution of the elements (Ahrens L. H., ed.), Pergamon, Oxford:125-143. [4] Cameron A. G. W. 1973. Space Science Revues 15:121-146. [5] Suess H. E. and Urey H. C. 1956. Revisions of Modern Physics 28:53-74. [6] Lodders K. 2010. in: Principles and Perspectives in Cosmochemistry. 379-417. [7] Meshik A. et all. 2011. 74th Meteoritical Society Meeting, Abstract#5471.

Improved genetically-encoded, FlincG-type fluorescent biosensors for neural cGMP imaging

PubMed Central

Bhargava, Yogesh; Hampden-Smith, Kathryn; Chachlaki, Konstantina; Wood, Katherine C.; Vernon, Jeffrey; Allerston, Charles K.; Batchelor, Andrew M.; Garthwaite, John

2013-01-01

Genetically-encoded biosensors are powerful tools for understanding cellular signal transduction mechanisms. In aiming to investigate cGMP signaling in neurones using the EGFP-based fluorescent biosensor, FlincG (fluorescent indicator for cGMP), we encountered weak or non-existent fluorescence after attempted transfection with plasmid DNA, even in HEK293T cells. Adenoviral infection of HEK293T cells with FlincG, however, had previously proved successful. Both constructs were found to harbor a mutation in the EGFP domain and had a tail of 17 amino acids at the C-terminus that differed from the published sequence. These discrepancies were systematically examined, together with mutations found beneficial for the related GCaMP family of Ca2+ biosensors, in a HEK293T cell line stably expressing both nitric oxide (NO)-activated guanylyl cyclase and phosphodiesterase-5. Restoring the mutated amino acid improved basal fluorescence whereas additional restoration of the correct C-terminal tail resulted in poor cGMP sensing as assessed by superfusion of either 8-bromo-cGMP or NO. Ultimately, two improved FlincGs were identified: one (FlincG2) had the divergent tail and gave moderate basal fluorescence and cGMP response amplitude and the other (FlincG3) had the correct tail, a GCaMP-like mutation in the EGFP region and an N-terminal tag, and was superior in both respects. All variants tested were strongly influenced by pH over the physiological range, in common with other EGFP-based biosensors. Purified FlincG3 protein exhibited a lower cGMP affinity (0.89 μM) than reported for the original FlincG (0.17 μM) but retained rapid kinetics and a 230-fold selectivity over cAMP. Successful expression of FlincG2 or FlincG3 in differentiated N1E-115 neuroblastoma cells and in primary cultures of hippocampal and dorsal root ganglion cells commends them for real-time imaging of cGMP dynamics in neural (and other) cells, and in their subcellular specializations. PMID:24068983

Chlorine Stable Isotopes to reveal contribution of magmatic chlorine in subduction zones: the case of the Kamchatka-Kuril and the Lesser Antilles Volcanic Arcs

NASA Astrophysics Data System (ADS)

Agrinier, Pierre; Shilobreeva, Svetlana; Bardoux, Gerard; Michel, Agnes; Maximov, Alexandr; Kalatcheva, Elena; Ryabinin, Gennady; Bonifacie, Magali

2015-04-01

By using the stable isotopes of chlorine (δ 37Cl), we have shown that magmatic chlorine (δ 37Cl ≤ -0.6 ‰ [1]) is different from surface chlorine (δ 37Cl ≈ 0 ‰ [1]) in hydrothermal system of Soufrière and Montagne Pelé from the young arc volcanic system of Lesser Antilles. First measurements on condensed chlorides from volcanic gases (e.g. [2], [3]) did not permitted to get sensible δ 37Cl values on degassed chlorine likely because chlorine isotopes are fractionated during the HClgas - chloride equilibrium in the fumaroles or during sampling artifacts. Therefore we have developed an alternative strategy based on the analysis of chloride in thermal springs, streams, sout{f}lowing on the flanks of the volcanoes. Due to the highly hydrophilic behavior of Cl, we hypothesize that thermal springs incorporate chlorine without fractionation of chlorine isotopes and might reflect the chlorine isotopic composition degassed by magmas [1]. Indeed Thermal spring with low δ 37Cl chlorides (≤ -0.6 perthousand{}) are linked with magmatic volatiles characters (3He ratio at 5 Ra at and δ 13C CO2 quad ≈ -3 perthousand{}). To go further in the potentiality of using the Chlorine isotopes to reveal contribution of magmatic chlorine in volcanic systems, we have started the survey of thermal springs and wells waters in the Kamchatka-Kuril volcanic mature Arc (on sites Mutnovsky, Paratunka, Nalychevsky, Khodutkinsky, Paramushir Island, identified by Taran, 2009 [4] for concentrations of chloride). Preliminary results show δ 37Cl values ranging from 0.5 to -0.2 ‰ and generally higher chloride concentrations. The δ 37Cl values are higher than the value recorded for the young arc volcanic system of lesser Antilles. At present moment very few negative δ 37Cl have been measured in the Kamchatka-Kuril volcanic mature Arc. [1] Li et al., 2015 EPSL in press. [2] Sharp et al. 2010 GCA. [3] Rizzo et al., 2013, EPSL, 371, 134. [4] Taran, 2009, GCA, 73, 1067

Noble Gas signatures of Enhanced Oil Recovery

NASA Astrophysics Data System (ADS)

Barry, P. H.; Kulongoski, J. T.; Tyne, R. L.; Hillegonds, D.; Byrne, D. J.; Landon, M. K.; Ballentine, C. J.

2017-12-01

Noble gases are powerful tracers of fluids from various oil and gas production activities in hydrocarbon reservoirs and nearby groundwater. Non-radiogenic noble gases are introduced into undisturbed oil and natural gas reservoirs through exchange with formation waters [1-3]. Reservoirs with extensive hydraulic fracturing, injection for enhanced oil recovery (EOR), and/or waste disposal also show evidence for a component of noble gases introduced from air [4]. Isotopic and elemental ratios of noble gases can be used to 1) assess the migration history of the injected and formation fluids, and 2) determine the extent of exchange between multiphase fluids in different reservoirs. We present noble gas isotope and abundance data from casing, separator and injectate gases of the Lost Hills and Fruitvale oil fields in the San Joaquin basin, California. Samples were collected as part of the California State Water Resource Control Board's Oil and Gas Regional Groundwater Monitoring Program. Lost Hills (n=7) and Fruitvale (n=2) gases are geochemically distinct and duplicate samples are highly reproducible. Lost Hills casing gas samples were collected from areas where EOR and hydraulic fracturing has occurred in the past several years, and from areas where EOR is absent. The Fruitvale samples were collected from a re-injection port. All samples are radiogenic in their He isotopes, typical of a crustal environment, and show enrichments in heavy noble gases, resulting from preferential adsorption on sediments. Fruitvale samples reflect air-like surface conditions, with higher air-derived noble gas concentrations. Lost Hills gases show a gradation from pristine crustal signatures - indicative of closed-system exchange with formation fluids - to strongly air-contaminated signatures in the EOR region. Pristine samples can be used to determine the extent of hydrocarbon exchange with fluids, whereas samples with excess air can be used to quantify the extent of EOR. Determining noble gas baseline values for pristine vs. recently modified (EOR, hydraulic fracturing) zones will be critical for interpreting the origin of any fugitive gases identified in nearby aquifers. [1] Ballentine et al., (1996) GCA, 60, 831-849 [2] Barry et al., (2016) GCA, 194, 291-309. [3] Barry et al., (2017) Geology, 45, 9. Darrah et al., (2014) PNAS 111, 39.

Uranium isotope fractionation in biogenic carbonates: biological effects

NASA Astrophysics Data System (ADS)

Chen, X.; Romaniello, S. J.; Herrmann, A. D.; Anbar, A. D.

2017-12-01

Recent laboratory experiments have demonstrated small but potentially significant isotope fractionation ( 0.10 ‰ for 238U/235U) during uranium (U) incorporation into abiotic calcite and aragonite, with heavier U isotopes preferentially enriched in the precipitates [1]. In contrast, measurements of natural biogenic carbonates to date have not been able to resolve significant U isotopic fractionation from seawater although this might be expected given a typical measurement precision of ± 0.10 ‰. Determining whether or not biogenic carbonates display U isotope fractionation similar to abiotic carbonates could have important implications for understanding the mechanisms of U incorporation into various biogenic carbonates. Furthermore, because most marine carbonates are biogenic, the extent of isotopic fractionation, if any, could have important implications for the interpretation of sedimentary carbonates record similar to effects observed for Cr and B isotopes [2, 3]. To resolve this discrepancy, we utilized a higher precision 238U/235U method which uses larger sample sizes to improve measurement precision of natural samples to ± 0.02 ‰ (2 se, N = 6) [4]. Using this method, we have surveyed 238U/235U in primary biogenic skeletal carbonates including scleractinian corals, green and red algae, and mollusks, as well as non-skeletal carbonates such as stromatolites, ooids, and carbonate sands from the Bahamas, Gulf of California, and French Polynesia. New high-precision U isotopes measurements reveal that biogenic skeletal carbonates are typically 0.02 - 0.08 ‰ heavier than modern seawater. Scleractinian corals display values closest to seawater (- 0.37 ‰), while green algae, red algae, mollusks, and echinoderms display variable but larger extents of fractionation up to 0.08 ‰. The direction and magnitude of U isotope fractionation in these biogenic precipitates are generally consistent with results from abiotic coprecipitation experiments, but may be subject to variations in U speciation and carbonate chemistry at calcification sites. [1] Chen et a., (2016), GCA, 188, 189-207. [2] Wang et a., (2016), Geobiology, 5, 51-64. [3] Pagani et al., (2005) GCA, 69, 953-961. [4] Andersen et al., (2016) CG, 420, 11-22.

Nuclear Planetology: Constraining the Driving Force in Wegener's Continental Drift Theory

NASA Astrophysics Data System (ADS)

Roller, G.

2015-12-01

Nuclear planetology [1] is a new research field, which aims at deciphering the nuclear physics processes responsible for the evolution of ultra-substellar objects and the driving force in Wegener's continental drift theory by means of Re-Os nuclear geochronometry [2]. Terrestrial Re/Os ratios observed within diamond sulphide inclusions [3], compatible with lunar r-process production ratios of Th/U≈1≈Au/Ir [4], drop from ≈0.8 to 0.2-0.05 for nucleogeochronometric ages between 2.3 Ga and 1.4 Ga [5]. It has therefore been argued [5,6] that the Re/Os fractionation is related to a change in oxygen fugacity due to the physics/chemistry of Earth's core after a possibly Fermi-pressure controlled core collapse [4]. Here, Pd/Ru, Pd/Pt, Pd/Ir, Pd/Os, Ru/Ir, Ru/Os, Pt/Ir or Pt/Os ratios from 24 published H chondrite components [7] are connected to their respective nucleogeochronometric ages to constrain an extended fossil fractionation record over 800 Ma. The following ranges are obtained: 0.06-1.04 (Pd/Ru), 0.06-0.79 (Pd/Pt), 0.06-1.76 (Pd/Os), 0.07-1.94 (Pd/Ir), 1.08-1.99 (Ru/Ir), 0.83-2.41 (Pt/Os), 0.82-2.64 (Pt/Ir). Comparing the Re/Os fractionation pattern of the diamond sulphide inclusions with these results and considering that Re is readily oxidized even at ultra-low oxygen fugacity, it may be concluded that (i) extremely reducing conditions within Earth's core basically preserve any unfractionated r-process element ratio until today; and (ii) nuclear/quantum physics processes leading to the observed ratios and fractionation pattern are ultimately the driving force in Wegener's continental drift theory. [1] Roller (2015), Abstract T34B-0407, AGU Spring Meeting. [2] Roller (2015), Geophys. Res. Abstr. 17, EGU2015-17. [3] Smit et al. (2010), GCA 74, 3292. [4] Roller (2015), Abstract #5041, 78th Ann. Met. Soc. Meeting. [5] Roller (2015), Geophys. Res. Abstr. 17, EGU2015-2399. [6] Roller (2015), Abstract PG34A-0283, AGU Spring Meeting. [7] Horan et al. (2009), GCA 73, 6984.

Origin and Role of Recycled Crust in Flood Basalt Magmatism: Case Study of the Central East Greenland Rifted Margin

NASA Astrophysics Data System (ADS)

Brown, E.; Lesher, C. E.

2015-12-01

Continental flood basalts (CFB) are extreme manifestations of mantle melting derived from chemically/isotopically heterogeneous mantle. Much of this heterogeneity comes from lithospheric material recycled into the convecting mantle by a range of mechanisms (e.g. subduction, delamination). The abundance and petrogenetic origins of these lithologies thus provide important constraints on the geodynamical origins of CFB magmatism, and the timescales of lithospheric recycling in the mantle. Basalt geochemistry has long been used to constrain the compositions and mean ages of recycled lithologies in the mantle. Typically, this work assumes the isotopic compositions of the basalts are the same as their mantle source(s). However, because basalts are mixtures of melts derived from different sources (having different fusibilities) generated over ranges of P and T, their isotopic compositions only indirectly represent the isotopic compositions of their mantle sources[1]. Thus, relating basalts compositions to mantle source compositions requires information about the melting process itself. To investigate the nature of lithologic source heterogeneity while accounting for the effects of melting during CFB magmatism, we utilize the REEBOX PRO forward melting model[2], which simulates adiabatic decompression melting in lithologically heterogeneous mantle. We apply the model to constrain the origins and abundance of mantle heterogeneity associated with Paleogene flood basalts erupted during the rift-to-drift transition of Pangea breakup along the Central East Greenland rifted margin of the North Atlantic igneous province. We show that these basalts were derived by melting of a hot, lithologically heterogeneous source containing depleted, subduction-modified lithospheric mantle, and <10% recycled oceanic crust. The Paleozoic mean age we calculate for this recycled crust is consistent with an origin in the region's prior subduction history, and with estimates for the mean age of recycled crust in the modern Iceland plume[3]. These results suggest that this lithospheric material was not recycled into the lower mantle before becoming entrained in the Iceland plume. [1] Rudge et al. (2013). GCA, 114, p112-143; [2] Brown & Lesher (2014). Nat. Geo., 7, p820-824; [3] Thirlwall et al. (2004). GCA, 68, p361-386

Phytophthora cinnamomi.

PubMed

Hardham, Adrienne R; Blackman, Leila M

2018-02-01

Phytophthora cinnamomi is one of the most devastating plant pathogens in the world. It infects close to 5000 species of plants, including many of importance in agriculture, forestry and horticulture. The inadvertent introduction of P. cinnamomi into natural ecosystems, including a number of recognized Global Biodiversity Hotspots, has had disastrous consequences for the environment and the biodiversity of flora and fauna. The genus Phytophthora belongs to the Class Oomycetes, a group of fungus-like organisms that initiate plant disease through the production of motile zoospores. Disease control is difficult in agricultural and forestry situations and even more challenging in natural ecosystems as a result of the scale of the problem and the limited range of effective chemical inhibitors. The development of sustainable control measures for the future management of P. cinnamomi requires a comprehensive understanding of the cellular and molecular basis of pathogen development and pathogenicity. The application of next-generation sequencing technologies to generate genomic and transcriptomic data promises to underpin a new era in P. cinnamomi research and discovery. The aim of this review is to integrate bioinformatic analyses of P. cinnamomi sequence data with current knowledge of the cellular and molecular basis of P. cinnamomi growth, development and plant infection. The goal is to provide a framework for future research by highlighting potential pathogenicity genes, shedding light on their possible functions and identifying suitable targets for future control measures. Phytophthora cinnamomi Rands; Kingdom Chromista; Phylum Oomycota or Pseudofungi; Class Oomycetes; Order Peronosporales; Family Peronosporaceae; genus Phytophthora. Infects about 5000 species of plants, including 4000 Australian native species. Host plants important for agriculture and forestry include avocado, chestnut, macadamia, oak, peach and pineapple. A root pathogen which causes rotting of fine and fibrous roots, but which can also cause stem cankers. Root damage may inhibit water movement from roots to shoots, leading to dieback of young shoots. USEFUL WEBSITES: http://fungidb.org/fungidb/; http://genome.jgi.doe.gov/Phyci1/Phyci1.home.html; http://www.ncbi.nlm.nih.gov/assembly/GCA_001314365.1; http://www.ncbi.nlm.nih.gov/assembly/GCA_001314505.1. © 2017 BSPP AND JOHN WILEY & SONS LTD.

Using gallium as a tracer of aluminum in the Critical Zone: influences on terrestrial cycling from vegetation.

NASA Astrophysics Data System (ADS)

Richardson, J. B.; Derry, L. A.

2016-12-01

Aluminum is a major component of primary and secondary aluminosilicate minerals, stabilizes of soil organic matter, and causes toxicity in plants and organisms. However, tracking the pathways and rates of Al cycling has been limited due to the lack of a suitable tracer because it is monoisotopic. Gallium (Ga) holds promise as an effective pseudo-isotope, geochemical tracer of Al (Shiller and Frilot, 1996, GCA). Gallium shares many physicochemical properties with Al. Both are Group 3A elements, with similar atomic radii, oxidation states, and charge densities. To determine fluxes of Al using the Ga/Al ratio, it is important to identify fractionation during weathering, secondary mineral precipitation, organic matter complexation, and vegetation cycling. To determine the extent of Ga/Al fractionation by vegetation, we measured Ga and Al in plant tissues and soils from three sites in the White Mountains of New Hampshire. Total Ga and Al were measured in late-season leaves and bolewood from Acer saccharum, Fagus grandifolia, and Picea rubens. In addition, we measured strong acid (16 M HNO3 + 12 M HCl) extractable Ga and Al throughout three Spodosol profiles. Gallium ranged between 0.10 - 0.17 nmol g-1 in plant tissues while soils ranged between 1.20 - 45.10 nmol g-1. Aluminum varied between 0.54 - 2.66 μmol g -1 in plant tissues and 7.70 - 263.60 μmol g -1 in their soils. The Ga/Al ratio varied significantly throughout the Critical Zone: late-season leaves (10 ± 1 nmol/ μmol) and bolewood (12 ± 1 nmol/ μmol), and organic horizons (6 ± 1 nmol/ μmol). Typical Ga/Al ratio in igneous and metamorphosed rocks is 0.10 ± 0.02 nmol/ μmol (Shiller and Frilot, 1996, GCA). Our results suggest that vegetation strongly accumulate Ga over Al during biological uplift. This study is one of the first to assess Ga biogeochemistry in the Critical Zone and more are needed, particularly for abiotic processes.

Modeling and Measuring the Effects of Radiation Damage Annealing on Helium Diffusion Kinetics in Apatite

NASA Astrophysics Data System (ADS)

Willett, C. D.; Fox, M.; Shuster, D. L.

2016-12-01

Understanding helium diffusion kinetics in apatite is critical for the accurate interpretation of (U-Th)/He thermochronometric data. This problem is complicated by the observation that helium diffusivity is not a simple function of temperature, but may evolve as a function of damage to the apatite crystal lattice resulting from alpha recoil. This `radiation damage' increases as a function of the amount of radiometric parent products, or effective uranium concentration, and time, but decreases due to thermal annealing of damage, necessitating a detailed understanding of radiation damage production and annealing in cases of burial heating over geologic timescales. Published observations [1,2] suggest that annealing rates of damage caused by alpha recoil and fission tracks in apatite differ. Existing models, however, assume the diffusion kinetics resulting from the two sources of damage are identical [3], demonstrating the need for further investigation of these damage sources. We present modeling and experimental work designed to interrogate the effects of radiation damage and its annealing on helium diffusion kinetics in apatite. Using previously published results [4] that investigated the effects of annealing temperature and duration on measured helium diffusivity, we fit a set of functions that are then integrated into a numerical model that tracks the evolution of radiation damage and apparent (U-Th)/He age. We compare the results of this model calibration to existing models [3]. In addition, we present data from two suites of diffusion experiments. The first suite, intended to test the published methodology and results, uses Durango apatite, while the second uses Sierran (CA) granite as a first test to determine if apatite of varying chemistry and age responds differently to the thermal annealing of radiation damage. Ultimately, the updated model and experimental results will benefit the interpretation of the effects of radiation damage accumulation and annealing in apatite and expand the range of geologic settings that can be studied using low-temperature thermochronology. References: [1] Fox, M., Shuster, D. (2014), EPSL 397, 174-183; [2] Gautheron, C. et al. (2013), Chem. Geol. 351, 257-267; [3] Flowers, R. et al. (2009), GCA 73, 2347-2365; [4] Shuster, D., Farley, K. (2009), GCA 73, 6183-6196.

Impact of indoor surface material on perceived air quality.

PubMed

Senitkova, I

2014-03-01

The material combination impact on perceived indoor air quality for various surface interior materials is presented in this paper. The chemical analysis and sensory assessments identifies health adverse of indoor air pollutants (TVOCs). In this study, emissions and odors from different common indoor surface materials were investigated in glass test chamber under standardized conditions. Chemical measurements (TVOC concentration) and sensory assessments (odor intensity, air acceptability) were done after building materials exposure to standardized conditions. The results of the chemical and sensory assessment of individual materials and their combinations are compared and discussed within the paper. The using possibility of individual material surface sorption ability was investigated. The knowledge of targeted sorption effects can be used in the interior design phase. The results demonstrate the various sorption abilities of various indoor materials as well as the various sorption abilities of the same indoor material in various combinations. Copyright © 2013 Elsevier B.V. All rights reserved.

Antibacterial activity and dentin bonding ability of combined use of Clearfil SE Protect and sodium hypochlorite.

PubMed

Muratovska, Ilijana; Kitagawa, Haruaki; Hirose, Nanako; Kitagawa, Ranna; Imazato, Satoshi

2018-02-08

The aim of this study was to evaluate the antibacterial activity and dentin bonding ability of a commercial self-etch adhesive Clearfil SE Protect (Kuraray Noritake Dental, Tokyo, Japan) in combination with sodium hypochlorite (NaOCl). Agar disc diffusion tests and measurement of minimum inhibitory/bactericidal concentrations (MIC/MBC) against Streptococcus mutans were performed to evaluate antibacterial effects. The mixture solution of 5.25% NaOCl and the primer of Clearfil SE Protect demonstrated less antibacterial activity than primer only. In microtensile bond strength tests using non-carious human molars, pretreatment with 5.25% NaOCl aqueous solution had no influence on the bond strength of Clearfil SE Protect. These results indicate that pretreatment with NaOCl does not influence the bonding ability of Clearfil SE Protect, while their combined use does not enhance cavity disinfecting effects.

Improving Reasoning Skills in Secondary History Education by Working Memory Training

ERIC Educational Resources Information Center

Ariës, Roel Jacobus; Groot, Wim; van den Brink, Henriette Maassen

2015-01-01

Secondary school pupils underachieve in tests in which reasoning abilities are required. Brain-based training of working memory (WM) may improve reasoning abilities. In this study, we use a brain-based training programme based on historical content to enhance reasoning abilities in history courses. In the first experiment, a combined intervention…

Do Interests and Cognitive Abilities Help Explain College Major Choice Equally Well for Women and Men?

ERIC Educational Resources Information Center

Passler, Katja; Hell, Benedikt

2012-01-01

The present study examines whether vocational interests, measured by Holland's RIASEC model, and objectively assessed cognitive abilities, were useful in discriminating among various major categories for a sample of 1990 German university students. Interests and specific abilities, in combination, significantly discriminated among major categories…

Developing combination immunotherapies for type 1 diabetes: recommendations from the ITN–JDRF Type 1 Diabetes Combination Therapy Assessment Group

PubMed Central

Matthews, J B; Staeva, T P; Bernstein, P L; Peakman, M; von Herrath, M

2010-01-01

Like many other complex human disorders of unknown aetiology, autoimmune-mediated type 1 diabetes may ultimately be controlled via a therapeutic approach that combines multiple agents, each with differing modes of action. The numerous advantages of such a strategy include the ability to minimize toxicities and realize synergies to enhance and prolong efficacy. The recognition that combinations might offer far-reaching benefits, at a time when few single agents have yet proved themselves in well-powered trials, represents a significant challenge to our ability to conceive and implement rational treatment designs. As a first step in this process, the Immune Tolerance Network, in collaboration with the Juvenile Diabetes Research Foundation, convened a Type 1 Diabetes Combination Therapy Assessment Group, the recommendations of which are discussed in this Perspective paper. PMID:20629979

[Shaping ability of two nickel-titanium rotary systems in simulated S-shaped canals].

PubMed

Luo, Hong-xia; Huang, Ding-ming; Zhang, Fu-hua; Tan, Hong; Zhou, Xue-dong

2008-01-01

To evaluate the shaping ability of two nickel-titanium rotary systems (ProTaper and Hero642) in simulated S-shaped canals. Thirty simulated S-shaped canals were randomly divided into three groups and prepared by ProTaper, Hero642, ProTaper combined with Hero642 respectively. All the canals were scanned before and after instrumentation, and the amount of material removed in the inner and outer wall and the canal width after instrumentation were measured with a computer image analysis program. There was significant difference in the amount of material removed at the inner side of apical curvature and outer side of apex between ProTaper combined with Hero642 and ProTaper files (P < 0.05) at the same tip size. The inner and outer wall of the canals were evenly prepared by ProTaper combined with Hero642, and the taper of canals were better than those prepared by Hero642. ProTaper combined with Hero 642 had better shaping ability to maintain the original shape and could create good taper canals in the simulated S-shaped canal model.

The combining of multiple hemispheric resources in learning-disabled and skilled readers' recall of words: a test of three information-processing models.

PubMed

Swanson, H L

1987-01-01

Three theoretical models (additive, independence, maximum rule) that characterize and predict the influence of independent hemispheric resources on learning-disabled and skilled readers' simultaneous processing were tested. Predictions related to word recall performance during simultaneous encoding conditions (dichotic listening task) were made from unilateral (dichotic listening task) presentations. The maximum rule model best characterized both ability groups in that simultaneous encoding produced no better recall than unilateral presentations. While the results support the hypothesis that both ability groups use similar processes in the combining of hemispheric resources (i.e., weak/dominant processing), ability group differences do occur in the coordination of such resources.

Tocilizumab (Actemra).

PubMed

Sheppard, Martin; Laskou, Faidra; Stapleton, Philip P; Hadavi, Shahryar; Dasgupta, Bhaskar

2017-09-02

Tocilizumab (TCZ), is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody which has a main use in the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis (sJIA) and polyarticular juvenile idiopathic arthritis (pJIA). This article provides an overview of TCZ including looking into the past at the discovery of interleukin-6 (IL-6) as a pro-inflammatory cytokine. It also looks at how tocilizumab was developed, manufactured and tested to ensure both safety and efficacy in a human population. The article then explores the advantages and disadvantages of using TCZ when compared to other biologics approved in RA, sJIA and pJIA and finally looks ahead to the future and the emerging role of IL-6 and its blockade by TCZ as a treatment for giant cell arteritis (GCA), polymyalgia rheumatica (PMR) and large vessel vasculitis (LVV).

Genome sequence and description of Corynebacterium ihumii sp. nov.

PubMed Central

Padmanabhan, Roshan; Dubourg, Grégory; Lagier, Jean-Christophe; Couderc, Carine; Michelle, Caroline; Raoult, Didier; Fournier, Pierre-Edouard

2014-01-01

Corynebacterium ihumii strain GD7T sp. nov. is proposed as the type strain of a new species, which belongs to the family Corynebacteriaceae of the class Actinobacteria. This strain was isolated from the fecal flora of a 62 year-old male patient, as a part of the culturomics study. Corynebacterium ihumii is a Gram positive, facultativly anaerobic, nonsporulating bacillus. Here, we describe the features of this organism, together with the high quality draft genome sequence, annotation and the comparison with other member of the genus Corynebacteria. C. ihumii genome is 2,232,265 bp long (one chromosome but no plasmid) containing 2,125 protein-coding and 53 RNA genes, including 4 rRNA genes. The whole-genome shotgun sequence of Corynebacterium ihumii strain GD7T sp. nov has been deposited in EMBL under accession number GCA_000403725. PMID:25197488

Expanded ATXN3 frameshifting events are toxic in Drosophila and mammalian neuron models.

PubMed

Stochmanski, Shawn J; Therrien, Martine; Laganière, Janet; Rochefort, Daniel; Laurent, Sandra; Karemera, Liliane; Gaudet, Rebecca; Vyboh, Kishanda; Van Meyel, Don J; Di Cristo, Graziella; Dion, Patrick A; Gaspar, Claudia; Rouleau, Guy A

2012-05-15

Spinocerebellar ataxia type 3 is caused by the expansion of the coding CAG repeat in the ATXN3 gene. Interestingly, a -1 bp frameshift occurring within an (exp)CAG repeat would henceforth lead to translation from a GCA frame, generating polyalanine stretches instead of polyglutamine. Our results show that transgenic expression of (exp)CAG ATXN3 led to -1 frameshifting events, which have deleterious effects in Drosophila and mammalian neurons. Conversely, transgenic expression of polyglutamine-encoding (exp)CAA ATXN3 was not toxic. Furthermore, (exp)CAG ATXN3 mRNA does not contribute per se to the toxicity observed in our models. Our observations indicate that expanded polyglutamine tracts in Drosophila and mouse neurons are insufficient for the development of a phenotype. Hence, we propose that -1 ribosomal frameshifting contributes to the toxicity associated with (exp)CAG repeats.

An extended retinotopic map of mouse cortex

PubMed Central

Zhuang, Jun; Ng, Lydia; Williams, Derric; Valley, Matthew; Li, Yang; Garrett, Marina; Waters, Jack

2017-01-01

Visual perception and behavior are mediated by cortical areas that have been distinguished using architectonic and retinotopic criteria. We employed fluorescence imaging and GCaMP6 reporter mice to generate retinotopic maps, revealing additional regions of retinotopic organization that extend into barrel and retrosplenial cortices. Aligning retinotopic maps to architectonic borders, we found a mismatch in border location, indicating that architectonic borders are not aligned with the retinotopic transition at the vertical meridian. We also assessed the representation of visual space within each region, finding that four visual areas bordering V1 (LM, P, PM and RL) display complementary representations, with overlap primarily at the central hemifield. Our results extend our understanding of the organization of mouse cortex to include up to 16 distinct retinotopically organized regions. DOI: http://dx.doi.org/10.7554/eLife.18372.001 PMID:28059700

A Longitudinal Field Study Comparing a Multiplicative and an Additive Model of Motivation and Ability. Technical Report No. 11.

ERIC Educational Resources Information Center

Barrett, Gerald V.; And Others

The relative contribution of motivation to ability measures in predicting performance criteria of sales personnel from successive fiscal periods was investigated. In this context, the merits of a multiplicative and additive combination of motivation and ability measures were examined. The relationship between satisfaction and motivation and…

Memory Abilities in Children with Mathematical Difficulties: Comorbid Language Difficulties Matter

ERIC Educational Resources Information Center

Reimann, Giselle; Gut, Janine; Frischknecht, Marie-Claire; Grob, Alexander

2013-01-01

The present study investigated cognitive abilities in children with difficulties in mathematics only (n = 48, M = 8 years and 5 months), combined mathematical and language difficulty (n = 27, M = 8 years and 1 month) and controls (n = 783, M = 7 years and 11 months). Cognitive abilities were measured with seven subtests, tapping visual perception,…

Predicting Bobsled Pushing Ability from Various Combine Testing Events.

PubMed

Tomasevicz, Curtis L; Ransone, Jack W; Bach, Christopher W

2018-03-12

The requisite combination of speed, power, and strength necessary for a bobsled push athlete coupled with the difficulty in directly measuring pushing ability makes selecting effective push crews challenging. Current practices by USA Bobsled and Skeleton (USABS) utilize field combine testing to assess and identify specifically selected performance variables in an attempt to best predict push performance abilities. Combine data consisting of 11 physical performance variables were collected from 75 subjects across two winter Olympic qualification years (2009 and 2013). These variables were sprints of 15-, 30-, and 60 m, a flying 30 m sprint, a standing broad jump, a shot toss, squat, power clean, body mass, and dry-land brake and side bobsled pushes. Discriminant Analysis (DA) in addition to Principle Component Analysis (PCA) was used to investigate two cases (Case 1: Olympians vs. non-Olympians; Case 2: National Team vs. non-National Team). Using these 11 variables, DA led to a classification rule that proved capable of identifying Olympians from non-Olympians and National Team members from non-National Team members with 9.33% and 14.67% misclassification rates, respectively. The PCA was used to find similar test variables within the combine that provided redundant or useless data. After eliminating the unnecessary variables, DA on the new combinations showed that 8 (Case 1) and 20 (Case 2) other combinations with fewer performance variables yielded misclassification rates as low as 6.67% and 13.33% respectively. Utilizing fewer performance variables can allow governing bodies in many other sports to create more appropriate combine testing that maximize accuracy, while minimizing irrelevant and redundant strategies.

[Effects of Acupuncture Intervention Combined with Rehabilitation on Standing-balance-walking Ability in Stroke Patients].

PubMed

Chu, Jia-mei; Bao, Ye-hua; Zhu, Min

2015-12-01

To observe the influence of acupuncture stimulation of lateral side of Tianzhu (para-BL 10), electroacupuncture (EA) stimulation of scalp-point Balance Area (MS 14), Motor Area (MS 6) and body acupoints combined with rehabilitation training on standing-balance and walking ability in stroke patients. A total of 145 stroke inpatients were randomly assigned to rehabilitation group (n=48), routine acupuncture group (n=49) and para-BL10 group (n = 48). Patients of the rehabilitation group received balance training and routine rehabilitation training treatment, those of the routine acupuncture group received acupuncture stimulation of scalp-points (MS 14, MS 6), body acupoints, balance training and routine rehabilitation training,and those of the para-BL10 group received acupuncture stimulation of lateral side of BL 10 combined with scalp-points of MS 14 and MS 6 and body acupoints, and balance training and routine rehabilitation training. The treatment was conducted once daily, 5 times per week, 8 weeks altogether. The patients' balancing function, lower-limb motor function and walking ability were assessed using Berg Balance Scale (BBS), Sheikh Trunk Control Ability Scale(STCAS), Fugl-Meyer Assessment Scale (FMAS), and Holden Functional Ambulation Classification (FAC), respectively. After 4 and 8 weeks' treatment, the scores of BBS, STCAS, FMAS and FAC in patients of the rehabilitation, routine acupuncture and para-BL10 groups were significantly increased and 10 meters-walking time obviously reduced in comparison with pre-treatment in the same one group (P<0.01). The effects of acupuncture stimulation of para-BL 10 were considerably better than both rehabilitation and routine acupuncture groups in raising BBS, STCAS, FMAS and FAC scores and in reducing 10 m-walking time (P<0.05). Acupuncture stimulation of lateral side of BL 10 combined with scalp-points has a significant benefit for stroke patients in standing-balance ability and walking ability.

Combining Frequency Doubling Technology Perimetry and Scanning Laser Polarimetry for Glaucoma Detection.

PubMed

Mwanza, Jean-Claude; Warren, Joshua L; Hochberg, Jessica T; Budenz, Donald L; Chang, Robert T; Ramulu, Pradeep Y

2015-01-01

To determine the ability of frequency doubling technology (FDT) and scanning laser polarimetry with variable corneal compensation (GDx-VCC) to detect glaucoma when used individually and in combination. One hundred ten normal and 114 glaucomatous subjects were tested with FDT C-20-5 screening protocol and the GDx-VCC. The discriminating ability was tested for each device individually and for both devices combined using GDx-NFI, GDx-TSNIT, number of missed points of FDT, and normal or abnormal FDT. Measures of discrimination included sensitivity, specificity, area under the curve (AUC), Akaike's information criterion (AIC), and prediction confidence interval lengths. For detecting glaucoma regardless of severity, the multivariable model resulting from the combination of GDx-TSNIT, number of abnormal points on FDT (NAP-FDT), and the interaction GDx-TSNIT×NAP-FDT (AIC: 88.28, AUC: 0.959, sensitivity: 94.6%, specificity: 89.5%) outperformed the best single-variable model provided by GDx-NFI (AIC: 120.88, AUC: 0.914, sensitivity: 87.8%, specificity: 84.2%). The multivariable model combining GDx-TSNIT, NAP-FDT, and interaction GDx-TSNIT×NAP-FDT consistently provided better discriminating abilities for detecting early, moderate, and severe glaucoma than the best single-variable models. The multivariable model including GDx-TSNIT, NAP-FDT, and the interaction GDx-TSNIT×NAP-FDT provides the best glaucoma prediction compared with all other multivariable and univariable models. Combining the FDT C-20-5 screening protocol and GDx-VCC improves glaucoma detection compared with using GDx or FDT alone.

Effects of combined physical and cognitive training on fitness and neuropsychological outcomes in healthy older adults

PubMed Central

Desjardins-Crépeau, Laurence; Berryman, Nicolas; Fraser, Sarah A; Vu, Thien Tuong Minh; Kergoat, Marie-Jeanne; Li, Karen ZH; Bosquet, Laurent; Bherer, Louis

2016-01-01

Purpose Physical exercise and cognitive training have been shown to enhance cognition among older adults. However, few studies have looked at the potential synergetic effects of combining physical and cognitive training in a single study. Prior trials on combined training have led to interesting yet equivocal results. The aim of this study was to examine the effects of combined physical and cognitive interventions on physical fitness and neuropsychological performance in healthy older adults. Methods Seventy-six participants were randomly assigned to one of four training combinations using a 2×2 factorial design. The physical intervention was a mixed aerobic and resistance training program, and the cognitive intervention was a dual-task (DT) training program. Stretching and toning exercises and computer lessons were used as active control conditions. Physical and cognitive measures were collected pre- and postintervention. Results All groups showed equivalent improvements in measures of functional mobility. The aerobic–strength condition led to larger effect size in lower body strength, independently of cognitive training. All groups showed improved speed of processing and inhibition abilities, but only participants who took part in the DT training, independently of physical training, showed increased task-switching abilities. The level of functional mobility after intervention was significantly associated with task-switching abilities. Conclusion Combined training did not yield synergetic effects. However, DT training did lead to transfer effects on executive performance in neuropsychological tests. Both aerobic-resistance training and stretching-toning exercises can improve functional mobility in older adults. PMID:27698558

Stretchable Transparent Electrode Arrays for Simultaneous Electrical and Optical Interrogation of Neural Circuits in Vivo.

PubMed

Zhang, Jing; Liu, Xiaojun; Xu, Wenjing; Luo, Wenhan; Li, Ming; Chu, Fangbing; Xu, Lu; Cao, Anyuan; Guan, Jisong; Tang, Shiming; Duan, Xiaojie

2018-05-09

Recent developments of transparent electrode arrays provide a unique capability for simultaneous optical and electrical interrogation of neural circuits in the brain. However, none of these electrode arrays possess the stretchability highly desired for interfacing with mechanically active neural systems, such as the brain under injury, the spinal cord, and the peripheral nervous system (PNS). Here, we report a stretchable transparent electrode array from carbon nanotube (CNT) web-like thin films that retains excellent electrochemical performance and broad-band optical transparency under stretching and is highly durable under cyclic stretching deformation. We show that the CNT electrodes record well-defined neuronal response signals with negligible light-induced artifacts from cortical surfaces under optogenetic stimulation. Simultaneous two-photon calcium imaging through the transparent CNT electrodes from cortical surfaces of GCaMP-expressing mice with epilepsy shows individual activated neurons in brain regions from which the concurrent electrical recording is taken, thus providing complementary cellular information in addition to the high-temporal-resolution electrical recording. Notably, the studies on rats show that the CNT electrodes remain operational during and after brain contusion that involves the rapid deformation of both the electrode array and brain tissue. This enables real-time, continuous electrophysiological monitoring of cortical activity under traumatic brain injury. These results highlight the potential application of the stretchable transparent CNT electrode arrays in combining electrical and optical modalities to study neural circuits, especially under mechanically active conditions, which could potentially provide important new insights into the local circuit dynamics of the spinal cord and PNS as well as the mechanism underlying traumatic injuries of the nervous system.

Cardiomyocyte Circadian Oscillations Are Cell-Autonomous, Amplified by β-Adrenergic Signaling, and Synchronized in Cardiac Ventricle Tissue

PubMed Central

Welsh, David K.

2016-01-01

Circadian clocks impact vital cardiac parameters such as blood pressure and heart rate, and adverse cardiac events such as myocardial infarction and sudden cardiac death. In mammals, the central circadian pacemaker, located in the suprachiasmatic nucleus of the hypothalamus, synchronizes cellular circadian clocks in the heart and many other tissues throughout the body. Cardiac ventricle explants maintain autonomous contractions and robust circadian oscillations of clock gene expression in culture. In the present study, we examined the relationship between intrinsic myocardial function and circadian rhythms in cultures from mouse heart. We cultured ventricular explants or dispersed cardiomyocytes from neonatal mice expressing a PER2::LUC bioluminescent reporter of circadian clock gene expression. We found that isoproterenol, a β-adrenoceptor agonist known to increase heart rate and contractility, also amplifies PER2 circadian rhythms in ventricular explants. We found robust, cell-autonomous PER2 circadian rhythms in dispersed cardiomyocytes. Single-cell rhythms were initially synchronized in ventricular explants but desynchronized in dispersed cells. In addition, we developed a method for long-term, simultaneous monitoring of clock gene expression, contraction rate, and basal intracellular Ca2+ level in cardiomyocytes using PER2::LUC in combination with GCaMP3, a genetically encoded fluorescent Ca2+ reporter. In contrast to robust PER2 circadian rhythms in cardiomyocytes, we detected no rhythms in contraction rate and only weak rhythms in basal Ca2+ level. In summary, we found that PER2 circadian rhythms of cardiomyocytes are cell-autonomous, amplified by adrenergic signaling, and synchronized by intercellular communication in ventricle explants, but we detected no robust circadian rhythms in contraction rate or basal Ca2+. PMID:27459195

Structural determinants of ligand binding in the ternary complex of human ileal bile acid binding protein with glycocholate and glycochenodeoxycholate obtained from solution NMR.

PubMed

Horváth, Gergő; Bencsura, Ákos; Simon, Ágnes; Tochtrop, Gregory P; DeKoster, Gregory T; Covey, Douglas F; Cistola, David P; Toke, Orsolya

2016-02-01

Besides aiding digestion, bile salts are important signal molecules exhibiting a regulatory role in metabolic processes. Human ileal bile acid binding protein (I-BABP) is an intracellular carrier of bile salts in the epithelial cells of the distal small intestine and has a key role in the enterohepatic circulation of bile salts. Positive binding cooperativity combined with site selectivity of glycocholate and glycochenodeoxycholate, the two most abundant bile salts in the human body, make human I-BABP a unique member of the family of intracellular lipid binding proteins. Solution NMR structure of the ternary complex of human I-BABP with glycocholate and glycochenodeoxycholate reveals an extensive network of hydrogen bonds and hydrophobic interactions stabilizing the bound bile salts. Conformational changes accompanying bile salt binding affects four major regions in the protein including the C/D, E/F and G/H loops as well as the helical segment. Most of these protein regions coincide with a previously described network of millisecond time scale fluctuations in the apo protein, a motion absent in the bound state. Comparison of the heterotypic doubly ligated complex with the unligated form provides further evidence of a conformation selection mechanism of ligand entry. Structural and dynamic aspects of human I-BABP-bile salt interaction are discussed and compared with characteristics of ligand binding in other members of the intracellular lipid binding protein family. The coordinates of the 10 lowest energy structures of the human I-BABP : GCDA : GCA complex as well as the distance restraints used to calculate the final ensemble have been deposited in the Brookhaven Protein Data Bank with accession number 2MM3. © 2015 FEBS.

PILOT STUDY: CCQM-P43: Tributyltin and dibutyltin in sediment

NASA Astrophysics Data System (ADS)

Wolff Briche, Céline S. J.; Wahlen, Raimund; Sturgeon, Ralph E.

2006-01-01

The pilot study CCQM P43 was undertaken to allow the assessment of the current capabilities of interested National Metrology Institutes (NIMs) (those which are members of the CCQM) and selected outside 'expert' laboratories for quantification of (C4H9)2Sn+ (DBT) and (C4H9)3Sn+ (TBT) in a prepared marine sediment. It was organised in parallel to the key comparison CCQM-K28, in which only NMIs determined TBT. This exercise was sanctioned by the 8th CCQM meeting, 18-19 April 2002, as an activity of the Inorganic Analysis Working Group and was jointly coordinated by the Institute for National Measurement Standards of the National Research Council of Canada (NRC) and LGC, UK. A total of 13 laboratories initially indicated interest (nine NMIs and four external laboratories). Only one external laboratory utilised a standard calibration approach based on natural abundance TBT and DBT standards, whereas all NMIs relied on isotope dilution mass spectrometry for quantitation (one NMI used ID-MS and an internal standard approach for the analysis of DBT). For this purpose, species specific 117Sn-enriched TBT and DBT standards were supplied by LGC. No sample preparation methodology was prescribed by the coordinating laboratories and, as a consequence, a variety of approaches was adopted by the participants, including mechanical shaking, sonication, accelerated solvent extraction, microwave assisted extraction and heating in combination with Grignard derivatization, ethylation and direct sampling. Detection techniques included ICP-MS (coupled to GC or HPLC), GC-MS and GC-AED. Main text. To reach the main text of this paper, click on Final Report. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the Mutual Recognition Arrangement (MRA).

Stimulation-evoked Ca2+ signals in astrocytic processes at hippocampal CA3-CA1 synapses of adult mice are modulated by glutamate and ATP.

PubMed

Tang, Wannan; Szokol, Karolina; Jensen, Vidar; Enger, Rune; Trivedi, Chintan A; Hvalby, Øivind; Helm, P Johannes; Looger, Loren L; Sprengel, Rolf; Nagelhus, Erlend A

2015-02-18

To date, it has been difficult to reveal physiological Ca(2+) events occurring within the fine astrocytic processes of mature animals. The objective of the study was to explore whether neuronal activity evokes astrocytic Ca(2+) signals at glutamatergic synapses of adult mice. We stimulated the Schaffer collateral/commissural fibers in acute hippocampal slices from adult mice transduced with the genetically encoded Ca(2+) indicator GCaMP5E driven by the glial fibrillary acidic protein promoter. Two-photon imaging revealed global stimulation-evoked astrocytic Ca(2+) signals with distinct latencies, rise rates, and amplitudes in fine processes and somata. Specifically, the Ca(2+) signals in the processes were faster and of higher amplitude than those in the somata. A combination of P2 purinergic and group I/II metabotropic glutamate receptor (mGluR) antagonists reduced the amplitude of the Ca(2+) transients by 30-40% in both astrocytic compartments. Blockage of the mGluRs alone only modestly reduced the magnitude of the stimulation-evoked Ca(2+) signals in processes and failed to affect the somatic Ca(2+) response. Local application of group I or I/II mGluR agonists or adenosine triphosphate (ATP) elicited global astrocytic Ca(2+) signals that mimicked the stimulation-evoked astrocytic Ca(2+) responses. We conclude that stimulation-evoked Ca(2+) signals in astrocytic processes at CA3-CA1 synapses of adult mice (1) differ from those in astrocytic somata and (2) are modulated by glutamate and ATP. Copyright © 2015 the authors 0270-6474/15/353016-06$15.00/0.

The influence of camouflage, obstruction, familiarity and spatial ability on target identification from an unmanned ground vehicle.

PubMed

Fincannon, Thomas; Keebler, Joseph R; Jentsch, Florian; Curtis, Michael

2013-01-01

The purpose of this study was to examine the effects of environmental and cognitive factors on the identification of targets from an unmanned ground vehicle (UGV). This was accomplished by manipulating obstruction, camouflage and familiarity of objects in the environment, while also measuring spatial ability. The effects of these variables on target identification were studied by measuring performance of participants that observed pre-recorded video from a 1:35 scaled military operations in urban terrain facility. Analyses indicated that a combination of camouflage and obstruction caused the most detrimental effects on performance, and that there were differences in the recognition of familiar and unfamiliar targets. Further analysis indicated that these detrimental effects could only be overcome with a combination of target familiarity and spatial ability. The findings highlight the degree to which environmental factors hinder performance and the need for a multidimensional approach for improving performance under these conditions. Areas in need of future research are also discussed. Cognitive theory is applied to the problem of perception from UGVs. Results from an experimental study indicate that a combination of camouflage and obstruction caused the most detrimental effects on performance, with differences in the recognition of both familiar and unfamiliar targets. Familiarity and spatial ability interacted to predict the performance.

Relative Frequencies of Arteritic and Nonarteritic Anterior Ischemic Optic Neuropathy in an Arab Population.

PubMed

Gruener, Anna M; Chang, Jessica R; Bosley, Thomas M; Al-Sadah, Zakeya M; Kum, Clarissa; McCulley, Timothy J

2017-12-01

To evaluate the relative frequencies of arteritic and nonarteritic anterior ischemic optic neuropathy (AION) in an Arab population and to compare and contrast these findings with known epidemiological data from Caucasian populations. A retrospective review of the medical records of all patients diagnosed with AION at the King Khaled Eye Specialist Hospital (KKESH) in Riyadh, Saudi Arabia, between 1997 and 2012. Of 171 patients with AION, 4 had biopsy-proven giant-cell arteritis (GCA). The relative frequencies of arteritic anterior ischemic optic neuropathy (AAION) and nonarteritic anterior ischemic optic neuropathy (NAION) in this Arab cohort were 2.3% and 97.7%, respectively. The relative frequencies of arteritic anterior ischemic optic neuropathy and nonarteritic anterior ischemic optic neuropathy differ between Arab and North American clinic-based populations, with giant-cell arteritis-related ischemia being much less frequent in Saudi Arabia.

Physico-chemical characterization of products from vacuum oil under delayed coking process by infrared spectroscopy and chemometrics methods

NASA Astrophysics Data System (ADS)

Meléndez, L. V.; Cabanzo, R.; Mejía-Ospino, E.; Guzmán, A.

2016-02-01

Eight vacuum residues and their delayed coking liquids products from Colombian crude were study by infrared spectroscopy with attenuated total reflectance (FTIR-ATR) and principal component analysis (PCA). For the samples the structural parameters of aromaticity factor (fa), alifaticity (A2500-3100cm-1), aromatic condensation degree (GCA), length of aliphatic chains (LCA) and aliphatic chain length associated with aromatic (LACAR) were determined through the development of a methodology, which includes the previous processing of spectroscopy data, identifying the regions in the IR spectra of greatest variance using PCA and molecules patterns. The parameters were compared with the results obtained from proton magnetic resonance (1H-NMR) and 13C-NMR. The results showed the influence and correlation of structural parameters with some physicochemical properties such as API gravity, weight percent sulphur (% S) and Conradson carbon content (% CCR)

Two-photon calcium imaging from head-fixed Drosophila during optomotor walking behavior.

PubMed

Seelig, Johannes D; Chiappe, M Eugenia; Lott, Gus K; Dutta, Anirban; Osborne, Jason E; Reiser, Michael B; Jayaraman, Vivek

2010-07-01

Drosophila melanogaster is a model organism rich in genetic tools to manipulate and identify neural circuits involved in specific behaviors. Here we present a technique for two-photon calcium imaging in the central brain of head-fixed Drosophila walking on an air-supported ball. The ball's motion is tracked at high resolution and can be treated as a proxy for the fly's own movements. We used the genetically encoded calcium sensor, GCaMP3.0, to record from important elements of the motion-processing pathway, the horizontal-system lobula plate tangential cells (LPTCs) in the fly optic lobe. We presented motion stimuli to the tethered fly and found that calcium transients in horizontal-system neurons correlated with robust optomotor behavior during walking. Our technique allows both behavior and physiology in identified neurons to be monitored in a genetic model organism with an extensive repertoire of walking behaviors.

Development of a new wheat germplasm with high anther culture ability by using a combination of gamma-ray irradiation and anther culture.

PubMed

Zhao, Linshu; Liu, Luxiang; Wang, Jing; Guo, Huijun; Gu, Jiayu; Zhao, Shirong; Li, Junhui; Xie, Yongdun

2015-01-01

Wheat with high anther culture ability would be beneficial for breeding. We aimed to screen a wheat germplasm to with high anther culture ability as well as good agronomic characteristics. The F1 young spikes of winter wheat cross combination Yanfu188/Jimai37 were irradiated with gamma rays at a dose of 1.5 Gy to develop a new germplasm H307 with high anther culture ability. The proportion of green plantlets per 100 anthers (GP/100A) of H307 was 14.50% which was higher than other H2 lines (P < 0.05). Analysis over three successive years (2006-2008) revealed that the green plantlet regeneration ability of H307 remained high in all 3 years. Reciprocal crosses between H307 and Nongda3308 showed no significant differences in their values for calli per 100 anthers (CA/100A), green plantlets per 100 calli (GP/100C) and GP/100A (P > 0.05). Five main wheat varieties used in production, namely Yumai68, Yanzhan4110, Bainongaikang58, Zhoumai18 and Xinmai18, were selected to cross with the new H307. CA/100A, GP/100C and GP/100A were used to assess the anther culture ability of F1 hybrids, demonstrating that the anther culture ability of H307 was heritable. H307 possessed high anther culture ability that was heritable, which would be potential germplasm for improving wheat anther breeding ability. © 2014 Society of Chemical Industry.

Predicting absenteeism: screening for work ability or burnout.

PubMed

Schouteten, R

2017-01-01

In determining the predictors of occupational health problems, two factors can be distinguished: personal (work ability) factors and work-related factors (burnout, job characteristics). However, these risk factors are hardly ever combined and it is not clear whether burnout or work ability best predicts absenteeism. To relate measures of work ability, burnout and job characteristics to absenteeism as the indicators of occupational health problems. Survey data on work ability, burnout and job characteristics from a Dutch university were related to the absenteeism data from the university's occupational health and safety database in the year following the survey study. The survey contained the Work Ability Index (WAI), Utrecht Burnout Scale (UBOS) and seven job characteristics from the Questionnaire on Experience and Evaluation of Work (QEEW). There were 242 employees in the study group. Logistic regression analyses revealed that job characteristics did not predict absenteeism. Exceptional absenteeism was most consistently predicted by the WAI dimensions 'employees' own prognosis of work ability in two years from now' and 'mental resources/vitality' and the burnout dimension 'emotional exhaustion'. Other significant predictors of exceptional absenteeism frequency included estimated work impairment due to diseases (WAI) and feelings of depersonalization or emotional distance from the work (burnout). Absenteeism among university personnel was best predicted by a combination of work ability and burnout. As a result, measures to prevent absenteeism and health problems may best be aimed at improving an individual's work ability and/or preventing the occurrence of burnout. © The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neural signatures of co-occurring reading and mathematical difficulties.

PubMed

Skeide, Michael A; Evans, Tanya M; Mei, Edward Z; Abrams, Daniel A; Menon, Vinod

2018-06-19

Impaired abilities in multiple domains is common in children with learning difficulties. Co-occurrence of low reading and mathematical abilities (LRLM) appears in almost every second child with learning difficulties. However, little is known regarding the neural bases of this combination. Leveraging a unique and tightly controlled sample including children with LRLM, isolated low reading ability (LR), and isolated low mathematical ability (LM), we uncover a distinct neural signature in children with co-occurring low reading and mathematical abilities differentiable from LR and LM. Specifically, we show that LRLM is neuroanatomically distinct from both LR and LM based on reduced cortical folding of the right parahippocampal gyrus, a medial temporal lobe region implicated in visual associative learning. LRLM children were further distinguished from LR and LM by patterns of intrinsic functional connectivity between parahippocampal gyrus and brain circuitry underlying reading and numerical quantity processing. Our results critically inform cognitive and neural models of LRLM by implicating aberrations in both domain-specific and domain-general brain regions involved in reading and mathematics. More generally, our results provide the first evidence for distinct multimodal neural signatures associated with LRLM, and suggest that this population displays an independent phenotype of learning difficulty that cannot be explained simply as a combination of isolated low reading and mathematical abilities. © 2018 John Wiley & Sons Ltd.

The Mode of Theoretical Knowledge and Practical Knowledge Combination: The Significance of Internship

ERIC Educational Resources Information Center

Yong, Tang

2012-01-01

In China, the conflict of university talents training program and market demands is increasingly attracting public attention. In order to satisfy the markets, the graduates should have abilities of combining theoretical knowledge with practice. Aiming at the issue of combining theoretical and practical knowledge, this paper takes construction…

Enhancing arabic bread quality and shelf life stability using bread improvers.

PubMed

Aleid, S M; Al-Hulaibi, A A; Ghoush, M Abu; Al-Shathri, A A

2015-08-01

Arabic breads is produced mainly from hard red winter wheat (HRWW) and have relatively little crumb, dense texture, form pocket and are often round with golden brown crust color. The objectives of this research were to investigate the effect of different bread improvers combinations addition in enhancing the quality parameters of Arabic bread. Therefore, the ability of Arabic bread for rolling, folding and overall quality were evaluated during the Arabic bread storage period for 2 days. It was found that there was significant effect of bread improvers combinations (Arabic gum "AG" * Mongglycerides "MG" *alpha-amylase) addition on the ability of Arabic bread for rolling and folding on the second day (P ≤ 0.1). The highest white Arabic bread quality was obtained significantly from addition of low AG, high of MG and high alpha-amylase combination and high AG, low of MG and high alpha-amylase combination. While, low of AG, high of MG and low alpha-amylase combination and high of AG, high of MG and low alpha-amylase combination significantly exhibited the highest overall quality for the Arabic bread made from whole flour.

Apyrase inhibitors enhance the ability of diverse fungicides to inhibit the growth of different plant-pathogenic fungi.

PubMed

Kumar Tripathy, Manas; Weeraratne, Gayani; Clark, Greg; Roux, Stanley J

2017-09-01

A previous study has demonstrated that the treatment of Arabidopsis plants with chemical inhibitors of apyrase enzymes increases their sensitivity to herbicides. In this study, we found that the addition of the same or related apyrase inhibitors could potentiate the ability of different fungicides to inhibit the growth of five different pathogenic fungi in plate growth assays. The growth of all five fungi was partially inhibited by three commonly used fungicides: copper octanoate, myclobutanil and propiconazole. However, when these fungicides were individually tested in combination with any one of four different apyrase inhibitors (AI.1, AI.10, AI.13 or AI.15), their potency to inhibit the growth of five fungal pathogens was increased significantly relative to their application alone. The apyrase inhibitors were most effective in potentiating the ability of copper octanoate to inhibit fungal growth, and least effective in combination with propiconazole. Among the five pathogens assayed, that most sensitive to the fungicide-potentiating effects of the inhibitors was Sclerotinia sclerotiorum. Overall, among the 60 treatment combinations tested (five pathogens, four apyrase inhibitors, three fungicides), the addition of apyrase inhibitors increased significantly the sensitivity of fungi to the fungicide treatments in 53 of the combinations. Consistent with their predicted mode of action, inhibitors AI.1, AI.10 and AI.13 each increased the level of propiconazole retained in one of the fungi, suggesting that they could partially block the ability of efflux transporters to remove propiconazole from these fungi. © 2016 BSPP AND JOHN WILEY & SONS LTD.

Combining Frequency Doubling Technology Perimetry and Scanning Laser Polarimetry for Glaucoma Detection

PubMed Central

Mwanza, Jean-Claude; Warren, Joshua L.; Hochberg, Jessica T.; Budenz, Donald L.; Chang, Robert T.; Ramulu, Pradeep Y.

2014-01-01

Purpose To determine the ability of frequency doubling technology (FDT) and scanning laser polarimetry with variable corneal compensation (GDx-VCC) to detect glaucoma when used individually and in combination. Methods One hundred and ten normal and 114 glaucomatous subjects were tested with FDT C-20-5 screening protocol and the GDx-VCC. The discriminating ability was tested for each device individually and for both devices combined using GDx-NFI, GDx-TSNIT, number of missed points of FDT, and normal or abnormal FDT. Measures of discrimination included sensitivity, specificity, area under the curve (AUC), Akaike’s information criterion (AIC), and prediction confidence interval lengths (PIL). Results For detecting glaucoma regardless of severity, the multivariable model resulting from the combination of GDX-TSNIT, number of abnormal points on FDT (NAP-FDT), and the interaction GDx-TSNIT * NAP-FDT (AIC: 88.28, AUC: 0.959, sensitivity: 94.6%, specificity: 89.5%) outperformed the best single variable model provided by GDx-NFI (AIC: 120.88, AUC: 0.914, sensitivity: 87.8%, specificity: 84.2%). The multivariable model combining GDx-TSNIT, NAPFDT, and interaction GDx-TSNIT*NAP-FDT consistently provided better discriminating abilities for detecting early, moderate and severe glaucoma than the best single variable models. Conclusions The multivariable model including GDx-TSNIT, NAP-FDT, and the interaction GDX-TSNIT * NAP-FDT provides the best glaucoma prediction compared to all other multivariable and univariable models. Combining the FDT C-20-5 screening protocol and GDx-VCC improves glaucoma detection compared to using GDx or FDT alone. PMID:24777046

Combination of hypothiocyanite and lactoferrin (ALX-109) enhances the ability of tobramycin and aztreonam to eliminate Pseudomonas aeruginosa biofilms growing on cystic fibrosis airway epithelial cells

PubMed Central

Moreau-Marquis, Sophie; Coutermarsh, Bonita; Stanton, Bruce A.

2015-01-01

Objectives Chelating iron may be a promising new therapy to eliminate Pseudomonas aeruginosa biofilms in the lungs of cystic fibrosis (CF) patients. Here, we investigate whether ALX-109 [a defined combination of an investigational drug containing lactoferrin (an iron-binding glycoprotein) and hypothiocyanite (a bactericidal agent)], alone and in combination with tobramycin or aztreonam, reduces P. aeruginosa biofilms grown on human CF airway epithelial cells. Methods P. aeruginosa (PAO1 and six clinical isolates of Pseudomonas) biofilms grown at the apical surface of confluent monolayers of CF airway epithelial cells were treated with ALX-109, either alone or in combination with tobramycin or aztreonam. Bacterial cfu remaining after treatment were determined by plate counting. Results ALX-109 alone reduced PAO1 biofilm formation, but had no effect on established biofilms. ALX-109 enhanced the ability of tobramycin and aztreonam to inhibit PAO1 biofilm formation and to reduce established PAO1 biofilms. ALX-109 and tobramycin were additive in disrupting established biofilms formed by six clinical isolates of P. aeruginosa obtained from the sputum of CF patients. Mucoid P. aeruginosa isolates were most susceptible to the combination of ALX-109 and tobramycin. In addition, ALX-109 also enhanced the ability of aztreonam to reduce established PAO1 biofilms. Conclusions Inhalation therapy combining hypothiocyanite and lactoferrin with TOBI® (tobramycin) or Cayston® (aztreonam) may be beneficial to CF patients by decreasing the airway bacterial burden of P. aeruginosa. PMID:25213272

Experimental high temperature carbon isotope fractionation involving graphite

NASA Astrophysics Data System (ADS)

Kueter, N.; Schmidt, M. W.; Lilley, M. D.; Bernasconi, S. M.

2016-12-01

Graphite/carbonate carbon isotope fractionation was mainly investigated at 400- 800°C and is based on empirical calibrations, theoretical calculations and few experiments [1,2]. Own work on COH-fluid/graphite isotope fractionation shows that in experiments up to 1000oC a fluid phase is always enriched in 13C compared to coexisting graphitic carbon. The eventual kinetic isotope effect in these experiments is best displayed by the graphitic carbon being at least 3 ‰ lighter than methane. Only few experiments done in the graphite/carbonate pair dealt with higher temperatures reaching 1400°C, indicating a fractionation of up to 2 ‰ at temperatures of the Earth's mantle [2-4]. To better understand carbon isotope fractionation in crustal systems and still overcome kinetic effects, we study the graphite/carbonatite pair with piston cylinder experiments in the Na2CO3-CaCO3-CaO-COH system. Tartaric acid (C4H6O6) supplies reduced carbon, time series are performed at 10 kbar, 1300-1800°C. Initial experiments at 1300°C produce well-ordered, micron-sized graphite flakes growing attached to the capsule walls while the Na-Ca-carbonatite-melt quenches to dendritic textures. No gaseous phase was observed. Conditions well above the liquidus of the Na2CO3-CaCO3-binary lead to dissolution of the H2O from tartaric acid decomposition in the melt, any CO2-component is bound by the excess CaO to CaCO3melt while in the relatively oxidizing capsule environment any CH4-component reacts with CO2 to carbon and H2O. The graphite and the carbonatite quench are measured for their δ13C composition using a GasBench II (carbonate-dissolution in phosphoric acid) and TC/EA (residual graphite combusted in oxygen atmosphere) system coupled to a Thermo Fischer IRMS. Our results expand from the graphite-carbonate system to graphite-fluid system when adding available fluid-carbonate fractionation factors, but are also directly applicable to diamond synthesis as graphite is often found as a precursor phase in diamond-growth experiments in carbonatite systems and natural diamonds. [1] Chacko et al. (2001) Rev Min Geochem; Deines & Eggler (2009) GCA; [3] Scheele & Hoefs (1992) CMP; [4] Chacko et al. (1991) GCA

Silicon isotope fractionations in pure Si and Fe-Si systems and their geological implications

NASA Astrophysics Data System (ADS)

Zheng, X. Y.; Beard, B. L.; Reddy, T. R.; Roden, E. E.; Johnson, C.

2016-12-01

Amorphous Si or Si-bearing materials are ubiquitous in nature, and are likely precursors to various rock types, such as cherts and banded iron formations (BIFs). Si isotope exchange kinetics and fractionation factors between these materials and aqueous Si, however, are poorly constrained, preventing a mechanistic or quantitative understanding of geological δ30Si records. A series of laboratory experiments were conducted to provide better estimates on Si isotope exchange kinetics and fractionation factors. Equilibrium Si isotope fractionation factors between Fe(III)-Si gel and aqueous Si (Δ30Sigel-aq) in artificial Archean seawater (AAS), determined by a three-isotope method with a 29Si tracer, are -2.3‰ where Fe2+ is absent from the solution, and -3.2‰ where Fe2+ is present in the solution[1]. Aqueous Fe2+ catalyzes Si isotope exchange, and causes larger Si isotope fractionation due to incorporation into the solid that may have changed Si bonding. In contrast, our preliminary results show that Δ30Sigel-aq between pure Si gel and aqueous Si at equilibrium is -0.13‰. Ongoing experiments are intended to approach the isotope equilibrium from multiple directions to resolve potential kinetic effects, and to explore temperature dependence. Nonetheless, the contrast in Δ30Sigel-aq between Fe-Si and pure Si systems highlights a significant impact of Fe on Si isotope fractionations. These results have important implications for Si isotopes in Precambrian cherts and BIFs, as well as in weathering systems in general. Silicon isotope fractionation was also studied in experiments that involved dissimilatory iron reduction of Fe(III)-Si gel by Desulfuromonas acetoxidans in AAS[2], and was found to become larger with progression of Fe reduction. A Δ30Sigel-aq of -3.5‰ was observed at 32% reduction of Fe3+. This result explains lower δ30Si values in magnetite-associated quartz that those in hematite-associated quartz in some BIFs. The large Si isotope fractionation produced in the microbial experiment, even larger than that seen in our Fe(II)-bearing abiologic experiments, suggests that δ30Si can be a potential tracer for magnetite of a microbial origin, or, vice versa, for microbial activities in magnetite. [1] Zheng et al., 2016, GCA 187, 102-122. [2] Reddy et al., 2016, GCA 190, 85-99.

High δ56Fe values in Samoan basalts

NASA Astrophysics Data System (ADS)

Konter, J. G.; Pietruszka, A. J.; Hanan, B. B.; Finlayson, V.

2014-12-01

Fe isotope fractionation spans ~0-0.4 permil in igneous systems, which cannot all be attributed to variable source compositions since peridotites barely overlap these compositions. Other processes may fractionate Fe isotopes such as variations in the degree of partial melting, magmatic differentiation, fluid addition related to the final stages of melt evolution, and kinetic fractionation related to diffusion. An important observation in igneous systems is the trend of increasing Fe isotope values against an index of magmatic fractionation (e.g. SiO2; [1]). The data strongly curve from δ56Fe >0.3 permil for SiO2 >70 wt% down to values around 0.09 permil from ~65 wt% down to 40 wt% SiO2 of basalts. However, ocean island basalts (OIBs) have a slightly larger δ56Fe variability than mid ocean ridge basalts (MORBs; [e.g. 2]). We present Fe isotope data on samples from the Samoan Islands (OIB) that have unusually high δ56Fe values for their SiO2 content. We rule out alteration by using fresh samples, and further test for the effects of magmatic processes on the δ56Fe values. In order to model the largest possible fractionation, unusually small degrees of melting with extreme fractionation factors are modeled with fractional crystallization of olivine alone, but such processing fails to fractionate the Fe isotopes to the observed values. Moreover, Samoan lavas likely also fractionated clinopyroxene, and its lower fractionation factor would limit the final δ56Fe value of the melt. We therefore suggest the mantle source of Samoan lavas must have had unusually high δ56Fe. However, there is no clear correlation with the highly radiogenic isotope signatures that reflect the unique source compositions of Samoa. Instead, increasing melt extraction correlates with lower δ56Fe values in peridotites assumed to be driven by the preference for the melt phase by heavy Fe3+, while high values may be related to metasomatism [3]. The latter would be in line with metasomatized xenoliths from Samoa [4]. [1] Heimann et al., 2008, doi:10.1016/j.gca.2008.06.009 [2] Teng et al., 2013, doi:10.1016/j.gca.2012.12.027 [3] Williams et al., 2004, doi: 10.1126/science.1095679 [4] Hauri et al., 1993, doi: 10.1038/365221a0

Ge and Fe Isotope Fractionation in Metabasites during Subduction-Zone Metamorphism

NASA Astrophysics Data System (ADS)

Luais, B.; El Korh, A. M. T.; Boiron, M. C.; Deloule, E.; Cividini, D.

2016-12-01

Non-traditional stable isotope fractionation during subduction of oceanic crust provides a powerful but challenging tool for understanding geochemical processes in the sub-arc mantle. Iron and germanium are strongly sensitive to low-temperature (T) hydrothermal processes (< 350°C), but can also fractionate at high-T (>700°C) [1-4]. We measured Fe and Ge isotopes in high-pressure metabasites of hydrothermally altered MORB (1.7-2.3 GPa; 550-600°C [5]) from the Ile de Groix (France) to study their behaviour during subduction and fluid-rock interactions. Eclogites and blueschists have δ74GeNIST3120a values (+0.42-0.65‰) similar to those of tholeiitic basalts (+0.55-0.57‰ [2]), indicating a negligible effect of hydrothermal alteration on δ74Ge values. Weak decreases in δ74Ge values occur during dehydration from blueschist to eclogite facies, and in greenschists showing evidence of restricted fluid-rock interaction, but remain close to the HP range (+0.39-0.49‰). This near constancy is attributed to stability of garnet, the main Ge host. By contrast, albite and calcite-bearing greenschists that suffer garnet breakdown show evidence of Ge isotope fractionation (δ74Ge = +0.84-0.98‰) during intensive fluid interaction in a reduced context (Fe2+/Fetot= 0.77-0.80). The metabasites have δ56FeIRMM-014 values (+0.16-0.33‰) heavier than MORBs-OIBs (+0.07-0.18‰ [3]). Unlike Ge isotopes, Fe isotopes correlate with HFSE and mainly reflect protolith heterogeneity. The increase in δ56Fe compared to igneous basic rocks results from open-system hydrothermal alteration prior to subduction. Small correlated variations in Fe elemental (Fe2+/Fetot) and isotopic compositions between blueschists, eclogites and greenschists suggest that Fe isotope fractionation was buffered by the iron of the basic protoliths during subduction and exhumation. Thus metasomatism related to fluids derived from subducted hydrothermally altered metabasites might have little effect on mantle Ge and Fe isotope compositions under subsolidus conditions. [1] Rouxel et al 2003, Chem Geol 202, 155-182. [2] Luais 2012. Chem Geol 334, 295-311. [3] Teng et al, 2013, GCA 107, 12-26. [4] Escoube et al 2015. GCA 167, 93-112. [5] El Korh et al 2009, J Petrol 50, 1107-1148.

Non-CI refractory lithophile abundances in bulk planetary materials

NASA Astrophysics Data System (ADS)

Dauphas, N.

2015-12-01

Refractory inclusions in meteorites show evidence for fractionation of refractory lithophile elements relative to one another. For bulk planetary materials, it is most often assumed that refractory lithophile elements (e.g., Ca, Al, Ti, REEs) are in proportions similar to CI carbonaceous chondrites, which is taken to be a proxy for solar composition. A diagnostic feature of REE patterns in refractory inclusions in meteorites is the presence of thulium anomalies, arising from the fact that this heavy REE is more volatile than the highly refractory HREEs surrounding it (Tm/Tm* is defined relative to either Er-Yb or Er-Lu). Tm anomalies thus represent an excellent diagnostic tool to test the assumption that refractory lithophile elements have uniform relative abundances at a bulk planetary scale. Prior to this work, high precision Tm measurements were lacking because it is mono-isotopic and as such is not amenable to high-precision single spike measurements. We have developed a multi-collector REE abundance measurement technique to measure all REEs at high precision, including the mono-isotopic ones. This technique was used to revise the abundance of CI and PAAS REE abundances (Pourmand et al. 2012) and the CI composition agrees well with an independent study (Barrat et al. 2012). The same technique was applied to measure REE patterns in 41 chondrites as well as terrestrial rocks (Dauphas and Pourmand, 2015). Our results reveal the presence of Tm anomalies of about -4.5 % in terrestrial rocks, enstatite and ordinary chondrites, relative to carbonaceous chondrites including CIs. This demonstrates that the assumption that refractory lithophile elements are in constant proportions among planetary bodies is unwarranted. It also shows that carbonaceous chondrites cannot be a major constituent of the Earth. The presence of Tm anomalies in meteorites and terrestrial rocks suggests that either (i) the material in the inner part of the solar system was formed from a gas reservoir that had been depleted in refractory dust or (ii) CI are enriched in refractory dust and are not representative of solar composition for refractory elements. Barrat J.A. et al. (2012) GCA 83, 79-92. Dauphas N., Pourmand A. (2015) GCA 163, 234-261. Pourmand et al. (2012) Chem. Geol. 291, 38-54.

Rapid Postnatal Expansion of Neural Networks Occurs in an Environment of Altered Neurovascular and Neurometabolic Coupling.

PubMed

Kozberg, Mariel G; Ma, Ying; Shaik, Mohammed A; Kim, Sharon H; Hillman, Elizabeth M C

2016-06-22

In the adult brain, increases in neural activity lead to increases in local blood flow. However, many prior measurements of functional hemodynamics in the neonatal brain, including functional magnetic resonance imaging (fMRI) in human infants, have noted altered and even inverted hemodynamic responses to stimuli. Here, we demonstrate that localized neural activity in early postnatal mice does not evoke blood flow increases as in the adult brain, and elucidate the neural and metabolic correlates of these altered functional hemodynamics as a function of developmental age. Using wide-field GCaMP imaging, the development of neural responses to somatosensory stimulus is visualized over the entire bilaterally exposed cortex. Neural responses are observed to progress from tightly localized, unilateral maps to bilateral responses as interhemispheric connectivity becomes established. Simultaneous hemodynamic imaging confirms that spatiotemporally coupled functional hyperemia is not present during these early stages of postnatal brain development, and develops gradually as cortical connectivity is established. Exploring the consequences of this lack of functional hyperemia, measurements of oxidative metabolism via flavoprotein fluorescence suggest that neural activity depletes local oxygen to below baseline levels at early developmental stages. Analysis of hemoglobin oxygenation dynamics at the same age confirms oxygen depletion for both stimulus-evoked and resting-state neural activity. This state of unmet metabolic demand during neural network development poses new questions about the mechanisms of neurovascular development and its role in both normal and abnormal brain development. These results also provide important insights for the interpretation of fMRI studies of the developing brain. This work demonstrates that the postnatal development of neuronal connectivity is accompanied by development of the mechanisms that regulate local blood flow in response to neural activity. Novel in vivo imaging reveals that, in the developing mouse brain, strong and localized GCaMP neural responses to stimulus fail to evoke local blood flow increases, leading to a state in which oxygen levels become locally depleted. These results demonstrate that the development of cortical connectivity occurs in an environment of altered energy availability that itself may play a role in shaping normal brain development. These findings have important implications for understanding the pathophysiology of abnormal developmental trajectories, and for the interpretation of functional magnetic resonance imaging data acquired in the developing brain. Copyright © 2016 the authors 0270-6474/16/366704-14$15.00/0.

REE and Isotopic Compositions of Lunar Basalts Demonstrate Partial Melting of Hybridized Mantle Sources after Cumulate Overturn is Required

NASA Astrophysics Data System (ADS)

Dygert, N. J.; Liang, Y.

2017-12-01

Lunar basalts maintain an important record of the composition of the lunar interior. Much of our understanding of the Moon's early evolution comes from studying their petrogenesis. Recent experimental work has advanced our knowledge of major and trace element fractionation during lunar magma ocean (LMO) crystallization [e.g., 1-3], which produced heterogeneous basalt sources in the Moon's mantle. With the new experimental constraints, we can evaluate isotopic and trace element signatures in lunar basalts in unprecedented detail, refining inferences about the Moon's dynamic history. Two petrogenetic models are invoked to explain the compositions of the basalts. The assimilation model argues they formed as primitive melts of early LMO cumulates that assimilated late LMO cumulates as they migrated upward. The cumulate overturn model argues that dense LMO cumulates sank into the lunar interior, producing hybridized sources that melted to form the basalts. Here we compare predicted Ce/Yb and Hf and Nd isotopes of partial melts of LMO cumulates with measured compositions of lunar basalts to evaluate whether they could have formed by end-member petrogenetic models. LMO crystallization models suggest all LMO cumulates have chondrite normalized Ce/Yb <1. Residual liquid from the magma ocean has Ce/Yb 1.5. Many primitive lunar basalts have Ce/Yb>1.5; these could not have formed by assimilation of any LMO cumulate or residual liquid (or KREEP basalt, which has isotopically negative ɛNd and ɛHf). In contrast, basalt REE patterns and isotopes can easily be modeled assuming partial melting of hybridized mantle sources, indicating overturn may be required. A chemical requirement for overturn independently confirms that late LMO cumulates are sufficiently low in viscosity to sink into the lunar interior, as suggested by recent rock deformation experiments [4]. Overturned, low viscosity late LMO cumulates would be relatively stable around the core [5]. High Ce/Yb basalts require that overturned cumulates were mixed back into the overlying mantle by convection within a few hundred Myr. [1] Dygert et al. (2014), GCA 132, 170-186. [2] Sun et al. (2017), GCA 206, 273-295. [3] Lin et al. (2017), EPSL 471, 104-116. [4] Dygert et al. (2016), GRL 43, 10.1002/2015GL066546. [5] Zhang et al. (2017), GRL 44, 10.1002/2017GL073702.

In vitro performance and principles of anti-siphoning devices.

PubMed

Freimann, Florian Baptist; Kimura, Takaoki; Stockhammer, Florian; Schulz, Matthias; Rohde, Veit; Thomale, Ulrich-Wilhelm

2014-11-01

Anti-siphon devices (ASDs) of various working principles were developed to overcome overdrainage-related complications associated with ventriculoperitoneal shunting. We aimed to provide comparative data on the pressure and flow characteristics of six different types of ASDs (gravity-assisted, membrane-controlled, and flow-regulated) in order to achieve a better understanding of these devices and their potential clinical application. We analyzed three gravity-dependent ASDs (ShuntAssistant [SA], Miethke; Gravity Compensating Accessory [GCA], Integra; SiphonX [SX], Sophysa), two membrane-controlled ASDs (Anti-Siphon Device [IASD], Integra; Delta Chamber [DC], Medtronic), and one flow-regulated ASD (SiphonGuard [SG], Codman). Defined pressure conditions within a simulated shunt system were generated (differential pressure 10-80 cmH2O), and the specific flow and pressure characteristics were measured. In addition, the gravity-dependent ASDs were measured in defined spatial positions (0-90°). The flow characteristics of the three gravity-assisted ASDs were largely dependent upon differential pressure and on their spatial position. All three devices were able to reduce the siphoning effect, but each to a different extent (flow at inflow pressure: 10 cmH2O, siphoning -20 cmH2O at 0°/90°: SA, 7.1 ± 1.2*/2.3 ±  0.5* ml/min; GCA, 10.5 ± 0.8/3.4 ± 0.4* ml/min; SX, 9.5 ± 1.2*/4.7 ± 1.9* ml/min, compared to control, 11.1 ± 0.4 ml/min [*p < 0.05]). The flow characteristics of the remaining ASDs were primarily dependent upon the inflow pressure effect (flow at 10 cmH2O, siphoning 0 cmH2O/ siphoning -20cmH2O: DC, 2.6 ± 0.1/ 4 ± 0.3* ml/min; IASD, 2.5 ± 0.2/ 0.8 ± 0.4* ml/min; SG, 0.8 ± 0.2*/ 0.2 ± 0.1* ml/min [*p < 0.05 vs. control, respectively]). The tested ASDs were able to control the siphoning effect within a simulated shunt system to differing degrees. Future comparative trials are needed to determine the type of device that is superior for clinical application.

Noble Gases as tracers of fluid migration in the Haynesville shale and overlying strata

NASA Astrophysics Data System (ADS)

Byrne, D. J.; Barry, P. H.; Lawson, M.; Ballentine, C. J.

2017-12-01

Noble gases are ideal tracers of physical processes and fluid provenance in crustal systems. Due to their inert nature, they are unaffected by chemical alteration, redox, or biological phenomena that fractionate other geochemical tracers. Noble gas analysis has been used to quantify fluid provenance, interactions, and ages in petroleum systems [1,2], but the effects of hydrocarbon migration on noble gas signatures have not been directly observed. The Haynesville Shale (East Texas & Louisiana), is exploited commercially for unconventional shale gas, but also acts as the source-rock for overlying conventional reservoirs. We present noble gas isotope and abundance data in samples collected from 9 natural gas wells sourced from the Haynesville Shale, as well as 21 from reservoirs in the overlying Cotton Valley (n=7), Travis Peak (n=9), and James (n=5) groups. Using a stratigraphic model, we observe systematic changes in the noble gas signatures as the fluids migrate from the Haynesville source rock to the overlying conventional accumulations. Helium isotope ratios (3He/4He) are strongly radiogenic in the Haynesville and stratigraphically older conventional reservoirs, with the younger reservoirs showing evidence of a mantle helium input. Argon isotope ratios (40Ar/36Ar) are strongly correlated with high 3He/4He, suggesting a similar provenance for radiogenic 40Ar and mantle 3He. Concentrations of groundwater-derived 36Ar are consistently higher in the conventional reservoirs than in the Haynesville shale, reflecting the greater interaction with groundwater during migration. However, 20Ne/36Ar ratios are not significantly different, suggesting that solubility-dependent partitioning is not simply dependent on vertical or horizontal migration distance. Krypton and xenon abundances are higher than expected for groundwater in all samples, a phenomenon that has been observed in many other hydrocarbon accumulations [3]. The excess Xe/Kr ratio is highest in the Haynesville itself, suggesting that this excess Xe and Kr originates from within the source-rock, and is subsequently shifted towards normal Xe/Kr values by mixing with groundwater-derived noble gases during migration. [1] Barry et al., 2016, GCA 194, 291-309; [2] Darrah et al., 2014, PNAS 111, 14076-81; [3] Zhou et al., 2005, GCA 69, 5413-28

Inhibition of presynaptic calcium transients in cortical inputs to the dorsolateral striatum by metabotropic GABAB and mGlu2/3 receptors

PubMed Central

Kupferschmidt, David A; Lovinger, David M

2015-01-01

Cortical inputs to the dorsolateral striatum (DLS) are dynamically regulated during skill learning and habit formation, and are dysregulated in disorders characterized by impaired action control. Therefore, a mechanistic investigation of the processes regulating corticostriatal transmission is key to understanding DLS-associated circuit function, behaviour and pathology. Presynaptic GABAB and group II metabotropic glutamate (mGlu2/3) receptors exert marked inhibitory control over corticostriatal glutamate release in the DLS, yet the signalling pathways through which they do so are unclear. We developed a novel approach using the genetically encoded calcium (Ca2+) indicator GCaMP6 to assess presynaptic Ca2+ in corticostriatal projections to the DLS. Using simultaneous photometric presynaptic Ca2+ and striatal field potential recordings, we report that relative to P/Q-type Ca2+ channels, N-type channels preferentially contributed to evoked presynaptic Ca2+ influx in motor cortex projections to, and excitatory transmission in, the DLS. Activation of GABAB or mGlu2/3 receptors inhibited both evoked presynaptic Ca2+ transients and striatal field potentials. mGlu2/3 receptor-mediated depression did not require functional N-type Ca2+ channels, but was attenuated by blockade of P/Q-type channels. These findings reveal presynaptic mechanisms of inhibitory modulation of corticostriatal function that probably contribute to the selection and shaping of behavioural repertoires. Key points Plastic changes at cortical inputs to the dorsolateral striatum (DLS) underlie skill learning and habit formation, so characterizing the mechanisms by which these inputs are regulated is important for understanding the neural basis of action control. We developed a novel approach using the genetically encoded calcium (Ca2+) indicator GCaMP6 and brain slice photometry to assess evoked presynaptic Ca2+ transients in cortical inputs to the DLS and study their regulation by GABAB and mGlu2/3 receptors. GABAB and mGlu2/3 receptor activation caused clear reductions in electrical stimulus-evoked presynaptic Ca2+ transients in corticostriatal inputs to the DLS. Functional P/Q-type voltage-gated Ca2+ channels were required for the normal inhibitory action of corticostriatal mGlu2/3 receptors. We provide direct evidence of presynaptic Ca2+ inhibition by G protein-coupled receptors at corticostriatal projections. PMID:25781000

Sulfur concentration of mare basalts at sulfide saturation at high pressures and temperatures-Implications for S in the lunar mantle

NASA Astrophysics Data System (ADS)

Ding, S.; Hough, T.; Dasgupta, R.

2016-12-01

Low estimate of S in the bulk silicate moon (BSM) [e.g., 1] suggests that sulfide in the lunar mantle is likely exhausted during melting. This agrees with estimates of HSE depletion in the BSM [2], but challenges the S-rich core proposed by previous studies [e.g., 3]. A key parameter to constrain the fate of sulfide during mantle melting is the sulfur carrying capacity of the mantle melts (SCSS). However, the SCSS of variably high-Ti lunar basalts at high P-Tare unknown. Basalt-sulfide melt equilibria experiments were run in graphite capsules using a piston cylinder at 1.0-2.5 GPa and 1400-1600 °C, on high-Ti (Apollo11, 11.1 wt.%; [4]) and intermediate-Ti (Luna16, 5 wt.%; [5]) mare basalts. At 1.5 GPa, SCSS of Apollo11 increases from 3940 ppm S to 5860 ppm, as temperature increases from 1400 °C to 1600 °C. And at 1500 °C, SCSS decreases from 5350 ppm S to 3830 ppm, as pressure increases from 1 to 2.5 GPa. SCSS of Luna16 shows a similar P-T dependence. Previous models [e.g., 6] tend to overestimate the SCSS values determined in our study, with the model overprediction increasing with increasing melt TiO2. Consequently, we derive a new SCSS parameterization for high-FeO* silicate melts of variable TiO2content. At multiple saturation points [e.g., 7], the SCSS of primary lunar melts is 3500-5500 ppm. With these values, 0.02-0.05 wt.% sulfide (70-200 ppm S) in the mantle can be consumed by 2-6% melting. In order to generate primary lunar basalts with S of 800-1000 ppm [1], sulfide in the mantle must be exhausted, and the mode of sulfide cannot exceed 0.025 wt.% (100 ppm S). This estimate corresponds with lower end values in the terrestrial mantle and further agrees with previous calculations of HSE depletion in the BSM [2]. [1] Hauri et al.,2015, EPSL; [2] Day et al.,2007, Science; [3] Jing et al., 2014, EPSL; [4] Synder et al.,1992, GCA; [5] Warren & Taylor, 2014, Treatise on Geochemistry; [6] Li & Ripley, 2009, Econ.Geol ; [7] Krawczynski & Grove, 2012, GCA.

On Combining Scores from Interest and Value Measures for Counseling.

ERIC Educational Resources Information Center

Pryor, Robert G. L.; Taylor, Neville B.

1986-01-01

Investigated the usefulness and the methods for combining vocational interests and work aspect preferences. Results indicated the Vocational Preference Inventory has greater discriminatory ability than the Work Aspect Preference Scale. Implications for counselors are given. (Author/BL)

Leadership for Learning: A Questionable Slogan?

ERIC Educational Resources Information Center

Husen, Peter

The answer to determining organizational outcomes is not the ill-defined concept of "leadership." Rather, it is a combination of two factors: the ability and opportunity to influence others, and the value and belief system of the individual. Ability to influence is a function of one's place within the bureaucratic, professional, political, and…