The 28S–18S rDNA intergenic spacer from Crithidia fasciculata: repeated sequences, length heterogeneity, putative processing sites and potential interactions between U3 small nucleolar RNA and the ribosomal RNA precursor

PubMed Central

Schnare, Murray N.; Collings, James C.; Spencer, David F.; Gray, Michael W.

2000-01-01

In Crithidia fasciculata, the ribosomal RNA (rRNA) gene repeats range in size from ∼11 to 12 kb. This length heterogeneity is localized to a region of the intergenic spacer (IGS) that contains tandemly repeated copies of a 19mer sequence. The IGS also contains four copies of an ∼55 nt repeat that has an internal inverted repeat and is also present in the IGS of Leishmania species. We have mapped the C.fasciculata transcription initiation site as well as two other reverse transcriptase stop sites that may be analogous to the A0 and A′ pre-rRNA processing sites within the 5′ external transcribed spacer (ETS) of other eukaryotes. Features that could influence processing at these sites include two stretches of conserved primary sequence and three secondary structure elements present in the 5′ ETS. We also characterized the C.fasciculata U3 snoRNA, which has the potential for base-pairing with pre-rRNA sequences. Finally, we demonstrate that biosynthesis of large subunit rRNA in both C.fasciculata and Trypanosoma brucei involves 3′-terminal addition of three A residues that are not present in the corresponding DNA sequences. PMID:10982863

Pharmacological enhancement of calcium-activated potassium channel function reduces the effects of repeated stress on fear memory

PubMed Central

Atchley, Derek; Hankosky, Emily R.; Gasparotto, Kaylyn; Rosenkranz, J. Amiel

2012-01-01

Repeated stress impacts emotion, and can induce mood and anxiety disorders. These disorders are characterized by imbalance of emotional responses. The amygdala is fundamental in expression of emotion, and is hyperactive in many patients with mood or anxiety disorders. Stress also leads to hyperactivity of the amygdala in humans. In rodent studies, repeated stress causes hyperactivity of the amygdala, and increases fear conditioning behavior that is mediated by the basolateral amygdala (BLA). Calcium-activated potassium (KCa) channels regulate BLA neuronal activity, and evidence suggests reduced small conductance KCa (SK) channel function in male rats exposed to repeated stress. Pharmacological enhancement of SK channels reverses the BLA neuronal hyperexcitability caused by repeated stress. However, it is not known if pharmacological targeting of SK channels can repair the effects of repeated stress on amygdala-dependent behaviors. The purpose of this study was to test whether enhancement of SK channel function reverses the effects of repeated restraint on BLA-dependent auditory fear conditioning. We found that repeated restraint stress increased the expression of cued conditioned fear in male rats. However, 1-EBIO (1 or 10 mg/kg) or CyPPA (5 mg/kg) administered 30 minutes prior to testing of fear expression brought conditioned freezing to control levels, with little impact on fear expression in control handled rats. These results demonstrate that enhancement of SK channel function can reduce the abnormalities of BLA-dependent fear memory caused by repeated stress. Furthermore, this indicates that pharmacological targeting of SK channels may provide a novel target for alleviation of psychiatric symptoms associated with amygdala hyperactivity. PMID:22487247

The Dark Side of Testing Memory: Repeated Retrieval Can Enhance Eyewitness Suggestibility

ERIC Educational Resources Information Center

Chan, Jason C. K.; LaPaglia, Jessica A.

2011-01-01

Eyewitnesses typically recount their experiences many times before trial. Such repeated retrieval can enhance memory retention of the witnessed event. However, recent studies (e.g., Chan, Thomas, & Bulevich, 2009) have found that initial retrieval can exacerbate eyewitness suggestibility to later misleading information--a finding termed…

The dark side of testing memory: repeated retrieval can enhance eyewitness suggestibility.

PubMed

Chan, Jason C K; Lapaglia, Jessica A

2011-12-01

Eyewitnesses typically recount their experiences many times before trial. Such repeated retrieval can enhance memory retention of the witnessed event. However, recent studies (e.g., Chan, Thomas, & Bulevich, 2009) have found that initial retrieval can exacerbate eyewitness suggestibility to later misleading information--a finding termed retrieval-enhanced suggestibility (RES). Here we examined the influence of multiple retrieval attempts on eyewitness suggestibility to subsequent misinformation. In four experiments, we systematically varied the number of initial tests taken (between zero and six), the delay between initial testing and misinformation exposure (~30 min or 1 week), and whether initial testing was manipulated between- or within-subjects. University undergraduate students were used as participants. Overall, we found that eyewitness suggestibility increased as the number of initial tests increased, but this RES effect was qualified by the delay and by whether initial testing occurred in a within- or between-subjects manner. Specifically, the within-subjects RES effect was smaller than the between-subjects RES effect, possibly because of the influence of retrieval-induced forgetting/facilitation (Chan, 2009) when initial testing was manipulated within subjects. Moreover, consistent with the testing effect literature (Roediger & Karpicke, 2006), the benefits of repeated testing on later memory were stronger after a 1-week delay than after a 30-min delay, thus reducing the negative impact of RES in long-term situations. These findings suggest that conditions that are likely to occur in criminal investigations can either increase (repeated testing) or reduce (delay) the influence of RES, thus further demonstrating the complex relationship between eyewitness memory and repeated retrieval.

Reliability, repeatability, and reproducibility of pulmonary transit time assessment by contrast enhanced echocardiography.

PubMed

Herold, Ingeborg H F; Saporito, Salvatore; Bouwman, R Arthur; Houthuizen, Patrick; van Assen, Hans C; Mischi, Massimo; Korsten, Hendrikus H M

2016-01-05

The aim of this study is to investigate the inter and intra-rater reliability, repeatability, and reproducibility of pulmonary transit time (PTT) measurement in patients using contrast enhanced ultrasound (CEUS), as an indirect measure of preload and left ventricular function. Mean transit times (MTT) were measured by drawing a region of interest (ROI) in right and left cardiac ventricle in the CEUS loops. Acoustic intensity dilution curves were obtained from the ROIs. MTTs were calculated by applying model-based fitting on the dilution curves. PTT was calculated as the difference of the MTTs. Eight raters with different levels of experience measured the PTT (time moment 1) and repeated the measurement within a week (time moment 2). Reliability and agreement were assessed using intra-class correlations (ICC) and Bland-Altman analysis. Repeatability was tested by estimating the variance of means (ANOVA) of three injections in each patient at different doses. Reproducibility was tested by the ICC of the two time moments. Fifteen patients with heart failure were included. The mean PTT was 11.8 ± 3.1 s at time moment 1 and 11.7 ± 2.9 s at time moment 2. The inter-rater reliability for PTT was excellent (ICC = 0.94). The intra-rater reliability per rater was between 0.81-0.99. Bland-Altman analysis revealed a bias of 0.10 s within the rater groups. Reproducibility for PTT showed an ICC = 0.94 between the two time moments. ANOVA showed no significant difference between the means of the three different doses F = 0.048 (P = 0.95). The mean and standard deviation for PTT estimates at three different doses was 11.6 ± 3.3 s. PTT estimation using CEUS shows a high inter- and intra-rater reliability, repeatability at three different doses, and reproducibility by ROI drawing. This makes the minimally invasive PTT measurement using contrast echocardiography ready for clinical evaluation in patients with heart failure and for preload estimation.

Intratumor distribution and test-retest comparisons of physiological parameters quantified by dynamic contrast-enhanced MRI in rat U251 glioma.

PubMed

Aryal, Madhava P; Nagaraja, Tavarekere N; Brown, Stephen L; Lu, Mei; Bagher-Ebadian, Hassan; Ding, Guangliang; Panda, Swayamprava; Keenan, Kelly; Cabral, Glauber; Mikkelsen, Tom; Ewing, James R

2014-10-01

The distribution of dynamic contrast-enhanced MRI (DCE-MRI) parametric estimates in a rat U251 glioma model was analyzed. Using Magnevist as contrast agent (CA), 17 nude rats implanted with U251 cerebral glioma were studied by DCE-MRI twice in a 24 h interval. A data-driven analysis selected one of three models to estimate either (1) plasma volume (vp), (2) vp and forward volume transfer constant (K(trans)) or (3) vp, K(trans) and interstitial volume fraction (ve), constituting Models 1, 2 and 3, respectively. CA distribution volume (VD) was estimated in Model 3 regions by Logan plots. Regions of interest (ROIs) were selected by model. In the Model 3 ROI, descriptors of parameter distributions--mean, median, variance and skewness--were calculated and compared between the two time points for repeatability. All distributions of parametric estimates in Model 3 ROIs were positively skewed. Test-retest differences between population summaries for any parameter were not significant (p ≥ 0.10; Wilcoxon signed-rank and paired t tests). These and similar measures of parametric distribution and test-retest variance from other tumor models can be used to inform the choice of biomarkers that best summarize tumor status and treatment effects. Copyright © 2014 John Wiley & Sons, Ltd.

Differential interaction and aggregation of 3-repeat and 4-repeat tau isoforms with 14-3-3{zeta} protein

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

Sadik, Golam; Tanaka, Toshihisa, E-mail: tanaka@psy.med.osaka-u.ac.jp; Kato, Kiyoko

2009-05-22

Tau isoforms, 3-repeat (3R) and 4-repeat tau (4R), are differentially involved in neuronal development and in several tauopathies. 14-3-3 protein binds to tau and 14-3-3/tau association has been found both in the development and in tauopathies. To understand the role of 14-3-3 in the differential regulation of tau isoforms, we have performed studies on the interaction and aggregation of 3R-tau and 4R-tau, either phosphorylated or unphosphorylated, with 14-3-3{zeta}. We show by surface plasmon resonance studies that the interaction between unphosphorylated 3R-tau and 14-3-3{zeta} is {approx}3-folds higher than that between unphosphorylated 4R-tau and 14-3-3{zeta}. Phosphorylation of tau by protein kinase Amore » (PKA) increases the affinity of both 3R- and 4R-tau for 14-3-3{zeta} to a similar level. An in vitro aggregation assay employing both transmission electron microscopy and fluorescence spectroscopy revealed the aggregation of unphosphorylated 4R-tau to be significantly higher than that of unphosphorylated 3R-tau following the induction of 14-3-3{zeta}. The filaments formed from 3R- and 4R-tau were almost similar in morphology. In contrast, the aggregation of both 3R- and 4R-tau was reduced to a similar low level after phosphorylation with PKA. Taken together, these results suggest that 14-3-3{zeta} exhibits a similar role for tau isoforms after PKA-phosphorylation, but a differential role for unphosphorylated tau. The significant aggregation of 4R-tau by 14-3-3{zeta} suggests that 14-3-3 may act as an inducer in the generation of 4R-tau-predominant neurofibrillary tangles in tauopathies.« less

Enhanced methane production via repeated batch bioaugmentation pattern of enriched microbial consortia.

PubMed

Yang, Zhiman; Guo, Rongbo; Xu, Xiaohui; Wang, Lin; Dai, Meng

2016-09-01

Using batch and repeated batch cultivations, this study investigated the effects of bioaugmentation with enriched microbial consortia (named as EMC) on methane production from effluents of hydrogen-producing stage of potato slurry, as well as on the indigenous bacterial community. The results demonstrated that the improved methane production and shift of the indigenous bacterial community structure were dependent on the EMC/sludge ratio and bioaugmentation patterns. The methane yield and production rate in repeated batch bioaugmentation pattern of EMC were, respectively, average 15% and 10% higher than in one-time bioaugmentation pattern of EMC. DNA-sequencing approach showed that the enhanced methane production in the repeated batch bioaugmentation pattern of EMC mainly resulted from the enriched iron-reducing bacteria and the persistence of the introduced Syntrophomonas, which led to a rapid degradation of individual VFAs to methane. The findings contributed to understanding the correlation between the bioaugmentation of microbial consortia, community shift, and methane production. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhancing consumer liking of low salt tomato soup over repeated exposure by herb and spice seasonings.

PubMed

Ghawi, Sameer Khalil; Rowland, Ian; Methven, Lisa

2014-10-01

There is strong evidence for the link between high dietary sodium and increased risk of cardiovascular disease which drives the need to reduce salt content in foods. In this study, herb and spice blends were used to enhance consumer acceptability of a low salt tomato soup (0.26% w/w). Subjects (n = 148) scored their liking of tomato soup samples over 5 consecutive days. The first and last days were pre-and post-exposure visits where all participants rated three tomato soup samples; standard, low salt and low salt with added herbs and spices. The middle 3 days were the repeated exposure phase where participants were divided into three balanced groups; consuming the standard soup, the low salt soup, or the low salt soup with added herbs and spices. Reducing salt in the tomato soup led to a significant decline in consumer acceptability, and incorporating herbs and spices did not lead to an immediate enhancement in liking. However, inclusion of herbs and spices enhanced the perception of the salty taste of the low salt soup to the same level as the standard. Repeated exposure to the herbs and spice-modified soup led to a significant increase in the overall liking and liking of flavour, texture and aftertaste of the soup, whereas no changes in liking were observed for the standard and low salt tomato soups over repeated exposure. Moreover, a positive trend in increasing the post-exposure liking of the herbs and spices soup was observed. The findings suggest that the use of herbs and spices is a useful approach to reduce salt content in foods; however, herbs and spices should be chosen carefully to complement the food as large contrasts in flavour can polarise consumer liking. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

ICAO helicopter noise measurement repeatability program : U.S. test report, Bell 206L-1, noise measurement flight test

DOT National Transportation Integrated Search

1985-09-30

This document reports the findings of the U.S. test team's participation in the Helicopter Noise Measurement Repeatability Program (HNMRP) conducted under the direction of the International Civil Aviation Organization's (ICAO) Committee on Aviation E...

The herpes simplex virus 1 U{sub S}3 regulates phospholipid synthesis

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

Wild, Peter, E-mail: pewild@access.uzh.ch; Institute of Virology, University of Zuerich; Oliveira, Anna Paula de

2012-10-25

Herpes simplex virus type 1 capsids bud at nuclear and Golgi membranes for envelopment by phospholipid bilayers. In the absence of U{sub S}3, nuclear membranes form multiple folds harboring virions that suggests disturbance in membrane turnover. Therefore, we investigated phospholipid metabolism in cells infected with the U{sub S}3 deletion mutant R7041({Delta}U{sub S}3), and quantified membranes involved in viral envelopment. We report that (i) [{sup 3}H]-choline incorporation into nuclear membranes and cytoplasmic membranes was enhanced peaking at 12 or 20 h post inoculation with wild type HSV-1 and R7041({Delta}U{sub S}3), respectively, (ii) the surface area of nuclear membranes increased until 24more » h of R7041({Delta}U{sub S}3) infection forming folds that equaled {approx}45% of the nuclear surface, (iii) the surface area of viral envelopes between nuclear membranes equaled {approx}2400 R7041({Delta}U{sub S}3) virions per cell, and (iv) during R7041({Delta}U{sub S}3) infection, the Golgi complex expanded dramatically. The data indicate that U{sub S}3 plays a significant role in regulation of membrane biosynthesis.« less

Effects of Repeated 3,4-Methylenedioxymethamphetamine Administration on Neurotransmitter Efflux and Sensory-Evoked Discharge in the Ventral Posterior Medial ThalamusS⃞

PubMed Central

Starr, M. A.; Page, M. E.

2012-01-01

3,4-Methylenedioxymethamphetamine (MDMA) is known to enhance tactile sensory perception, an effect that contributes to its popularity as a recreational drug. The neurophysiological basis for the effects of MDMA on somatosensation are unknown. However, MDMA interactions with the serotonin transporter (SERT) and subsequent enhancement of serotonin neurotransmission are well known. The rat trigeminal somatosensory system receives serotonergic afferents from the dorsal raphe nucleus. Because these fibers express SERT, they should be vulnerable to MDMA-induced effects. We found that administration of a challenge injection of MDMA (3 mg/kg i.p.) after repeated MDMA treatment (3 mg/kg per day for 4 days) elicits both serotonin and norepinephrine efflux in the ventral posterior medial (VPM) thalamus of Long-Evans hooded rats, the main relay along the lemniscal portion of the rodent trigeminal somatosensory pathway. We evaluated the potential for repeated MDMA administration to modulate whisker-evoked discharge of individual neurons in this region. After surgically implanting stainless steel eight-wire multichannel electrode bundles, we recorded spike train activity of single cells while activating the whisker pathway using a piezoelectric mechanical stimulator. We found that repeated MDMA administration increased the spontaneous firing rate but reduced both the magnitude and duration of whisker-evoked discharge in individual VPM thalamic neurons. The time course of drug action on neuronal firing patterns was generally consistent with fluctuations in neurotransmitter efflux as shown from our microdialysis studies. On the basis of these results, we propose that single use and repeated administration of MDMA may “distort,” rather than enhance, tactile experiences in humans, in part, by disrupting normal spike firing patterns through somatosensory thalamic relay circuits. PMID:21984836

Lower neurocognitive function in U-2 pilots

PubMed Central

Tate, David F.; Wood, Joe; Sladky, John H.; McDonald, Kent; Sherman, Paul M.; Kawano, Elaine S.; Rowland, Laura M.; Patel, Beenish; Wright, Susan N.; Hong, Elliot; Rasmussen, Jennifer; Willis, Adam M.; Kochunov, Peter V.

2014-01-01

Objective: Determine whether United States Air Force (USAF) U-2 pilots (U2Ps) with occupational exposure to repeated hypobaria had lower neurocognitive performance compared to pilots without repeated hypobaric exposure and whether U2P neurocognitive performance correlated with white matter hyperintensity (WMH) burden. Methods: We collected Multidimensional Aptitude Battery–II (MAB-II) and MicroCog: Assessment of Cognitive Functioning (MicroCog) neurocognitive data on USAF U2Ps with a history of repeated occupational exposure to hypobaria and compared these with control data collected from USAF pilots (AFPs) without repeated hypobaric exposure (U2Ps/AFPs MAB-II 87/83; MicroCog 93/80). Additional comparisons were performed between U2Ps with high vs low WMH burden. Results: U2Ps with repeated hypobaric exposure had significantly lower scores than control pilots on reasoning/calculation (U2Ps/AFPs 99.4/106.5), memory (105.5/110.9), information processing accuracy (102.1/105.8), and general cognitive functioning (103.5/108.5). In addition, U2Ps with high whole-brain WMH count showed significantly lower scores on reasoning/calculation (high/low 96.8/104.1), memory (102.9/110.2), general cognitive functioning (101.5/107.2), and general cognitive proficiency (103.6/108.8) than U2Ps with low WMH burden (high/low WMH mean volume 0.213/0.003 cm3 and mean count 14.2/0.4). Conclusion: In these otherwise healthy, highly functioning individuals, pilots with occupational exposure to repeated hypobaria demonstrated lower neurocognitive performance, albeit demonstrable on only some tests, than pilots without repeated exposure. Furthermore, within the U2P population, higher WMH burden was associated with lower neurocognitive test performance. Hypobaric exposure may be a risk factor for subtle changes in neurocognition. PMID:25008397

Reward modulation of contextual cueing: Repeated context overshadows repeated target location.

PubMed

Sharifian, Fariba; Contier, Oliver; Preuschhof, Claudia; Pollmann, Stefan

2017-10-01

Contextual cueing can be enhanced by reward. However, there is a debate if reward is associated with the repeated target-distractor configurations or with the repeated target locations that occur in both repeated and new displays. Based on neuroimaging evidence, we hypothesized that reward becomes associated with the target location only in new displays, but not in repeated displays, where the repeated target location is overshadowed by the more salient repeated target-distractor configuration. To test this hypothesis, we varied the reward value associated with the same target location in repeated and new displays. The results confirmed the overshadowing hypothesis in that search facilitation in repeated target-distractor configurations was modulated by the variable value associated with the target location. This effect was observed mainly in early learning.

Repeated immobilization stress increases uncoupling protein 1 expression and activity in Wistar rats.

PubMed

Gao, Bihu; Kikuchi-Utsumi, Kazue; Ohinata, Hiroshi; Hashimoto, Masaaki; Kuroshima, Akihiro

2003-06-01

Repeat immobilization-stressed rats are leaner and have improved cold tolerance due to enhancement of brown adipose tissue (BAT) thermogenesis. This process likely involves stress-induced sympathetic nervous system activation and adrenocortical hormone release, which dynamically enhances and suppresses uncoupling protein 1 (UCP1) function, respectively. To investigate whether repeated immobilization influences UCP1 thermogenic properties, we assessed UCP1 mRNA, protein expression, and activity (GDP binding) in BAT from immobilization-naive or repeatedly immobilized rats (3 h daily for 4 weeks) and sham operated or adrenalectomized (ADX) rats. UCP1 properties were assessed before (basal) and after exposure to 3 h of acute immobilization. Basal levels of GDP binding and UCP1 expression was significantly increased (140 and 140%) in the repeated immobilized group. Acute immobilization increased GDP binding in both naive (180%) and repeated immobilized groups (220%) without changing UCP1 expression. In ADX rats, basal GDP binding and UCP1 gene expression significantly increased (140 and 110%), and acute immobilization induced further increase. These data demonstrate that repeated immobilization resulted in enhanced UCP1 function, suggesting that enhanced BAT thermogenesis contributes to lower body weight gain through excess energy loss and an improved ability to maintain body temperature during cold exposure.

Synergistic enhancement of cellulase pairs linked by consensus ankyrin repeats: determination of the roles of spacing, orientation and enzyme identity

PubMed Central

Cunha, Eva S.; Hatem, Christine L.; Barrick, Doug

2017-01-01

Biomass deconstruction to small simple sugars is a potential approach to biofuels production, however the highly recalcitrant nature of biomass limits the economic viability of this approach. Thus, research on efficient biomass degradation is necessary to achieve large-scale production of biofuels. Enhancement of cellulolytic activity by increasing synergism between cellulase enzymes holds promise in achieving high-yield biofuels production. Here we have inserted cellulase pairs from extremophiles into hyper-stable α-helical consensus ankyrin repeat domain scaffolds. Such chimeric constructs allowed us to optimize arrays of enzyme pairs against a variety of cellulolytic substrates. We found that endocellulolytic domains CelA (CA) and Cel12A (C12A) act synergistically in the context of ankyrin repeats, with both three and four repeat spacing. The extent of synergy differs for different substrates. Also, having C12A N-terminal to CA provides greater synergy than the reverse construct, especially against filter paper. In contrast, we do not see synergy for these enzymes in tandem with CelK (CK) catalytic domain, a larger exocellulase, demonstrating the importance of enzyme identity in synergistic enhancement. Furthermore, we found endocellulases CelD and CA with three repeat spacing to act synergistically against filter paper. Importantly, connecting CA and C12A with a disordered linker of similar contour length, shows no synergistic enhancement, indicating that synergism results from connecting these domains with folded ankyrin repeats. These results show that ankyrin arrays can be used to vary spacing and orientation between enzymes, helping to design and optimize artificial cellulosomes, providing a novel architecture for synergistic enhancement of enzymatic cellulose degradation. PMID:27071357

Crosstalk between MSH2-MSH3 and polβ promotes trinucleotide repeat expansion during base excision repair.

PubMed

Lai, Yanhao; Budworth, Helen; Beaver, Jill M; Chan, Nelson L S; Zhang, Zunzhen; McMurray, Cynthia T; Liu, Yuan

2016-08-22

Studies in knockout mice provide evidence that MSH2-MSH3 and the BER machinery promote trinucleotide repeat (TNR) expansion, yet how these two different repair pathways cause the mutation is unknown. Here we report the first molecular crosstalk mechanism, in which MSH2-MSH3 is used as a component of the BER machinery to cause expansion. On its own, pol β fails to copy TNRs during DNA synthesis, and bypasses them on the template strand to cause deletion. Remarkably, MSH2-MSH3 not only stimulates pol β to copy through the repeats but also enhances formation of the flap precursor for expansion. Our results provide direct evidence that MMR and BER, operating together, form a novel hybrid pathway that changes the outcome of TNR instability from deletion to expansion during the removal of oxidized bases. We propose that cells implement crosstalk strategies and share machinery when a canonical pathway is ineffective in removing a difficult lesion.

MAP30 promotes apoptosis of U251 and U87 cells by suppressing the LGR5 and Wnt/β-catenin signaling pathway, and enhancing Smac expression

PubMed Central

Jiang, Yilin; Miao, Junjie; Wang, Dongliang; Zhou, Jingru; Liu, Bo; Jiao, Feng; Liang, Jiangfeng; Wang, Yangshuo; Fan, Cungang; Zhang, Qingjun

2018-01-01

Significant antitumor activity of Momordica anti-human immunodeficiency virus protein of 30 kDa (MAP30) purified from Momordica charantia has been the subject of previous research. However, the effective mechanism of MAP30 on malignant glioma cells has not yet been clarified. The aim of the present study was to investigate the effects and mechanism of MAP30 on U87 and U251 cell lines. A Cell Counting Kit-8 assay, wound healing assay and Transwell assay were used to detect the effects on U87 and U251 cells treated with different concentrations of MAP30 (0.5, 1, 2, 4, 8 and 16 µM) over different periods of time. Proliferation, migration and invasion of each cell line were markedly inhibited by MAP30 in a dose- and time-dependent manner. Flow cytometry and fluorescence staining demonstrated that apoptosis increased and the cell cycle was arrested in S-phase in the two investigated cell lines following MAP30 treatment. Western blot analysis demonstrated that leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) expression and key proteins in the Wnt/β-catenin signaling pathway were apparently decreased, whereas second mitochondria-derived activator of caspase (Smac) protein expression significantly increased with MAP30 treatment in the same manner. These results suggest that MAP30 markedly induces apoptosis in U87 and U251 cell lines by suppressing LGR5 and the Wnt/β-catenin signaling pathway, and enhancing Smac expression in a dose- and time-dependent manner. PMID:29556310

Synergistic enhancement of cellulase pairs linked by consensus ankyrin repeats: Determination of the roles of spacing, orientation, and enzyme identity.

PubMed

Cunha, Eva S; Hatem, Christine L; Barrick, Doug

2016-08-01

Biomass deconstruction to small simple sugars is a potential approach to biofuels production; however, the highly recalcitrant nature of biomass limits the economic viability of this approach. Thus, research on efficient biomass degradation is necessary to achieve large-scale production of biofuels. Enhancement of cellulolytic activity by increasing synergism between cellulase enzymes holds promise in achieving high-yield biofuels production. Here we have inserted cellulase pairs from extremophiles into hyperstable α-helical consensus ankyrin repeat domain scaffolds. Such chimeric constructs allowed us to optimize arrays of enzyme pairs against a variety of cellulolytic substrates. We found that endocellulolytic domains CelA (CA) and Cel12A (C12A) act synergistically in the context of ankyrin repeats, with both three and four repeat spacing. The extent of synergy differs for different substrates. Also, having C12A N-terminal to CA provides greater synergy than the reverse construct, especially against filter paper. In contrast, we do not see synergy for these enzymes in tandem with CelK (CK) catalytic domain, a larger exocellulase, demonstrating the importance of enzyme identity in synergistic enhancement. Furthermore, we found endocellulases CelD and CA with three repeat spacing to act synergistically against filter paper. Importantly, connecting CA and C12A with a disordered linker of similar contour length shows no synergistic enhancement, indicating that synergism results from connecting these domains with folded ankyrin repeats. These results show that ankyrin arrays can be used to vary spacing and orientation between enzymes, helping to design and optimize artificial cellulosomes, providing a novel architecture for synergistic enhancement of enzymatic cellulose degradation. Proteins 2016; 84:1043-1054. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Electrowinning of U-Pu onto inert solid cathode in LiCl-KCl eutectic melts containing UCl3 and PuCl3

NASA Astrophysics Data System (ADS)

Sakamura, Yoshiharu; Murakami, Tsuyoshi; Tada, Kohei; Kitawaki, Shinichi

2018-04-01

Electrowinning process was investigated for extracting actinides from molten salts used for the pyrochemical reprocessing of spent nuclear fuels. The separation of actinides from lanthanides is expected to be enhanced by employing inert solid cathodes due to larger potential differences on these cathodes. In this study, the co-deposition behavior of Pu and U metals onto an inert solid cathode made of tungsten was examined in LiCl-KCl eutectic melts containing UCl3 and PuCl3 at 773 K. The standard potential of U3+/U is 0.31 V more positive than that of Pu3+/Pu. The U3+ concentration was varied in the range of 0.11-0.66 wt%, while the Pu3+ concentration was maintained at approximately 2.9 wt%. When the U3+ concentration was not sufficiently low, the deposited U metal readily grew outward from the electrode surface and the electrode surface area rapidly increased, which facilitated only the deposition of U metal. It was estimated that metallic Pu can be efficiently collected along with U at U3+ concentrations lower than ∼0.2 wt%.

^2^3^8U/^2^3^5U Ratios of Anagrams: Angrites and Granites

NASA Astrophysics Data System (ADS)

Tissot, F. L. H.; Dauphas, N.

2012-03-01

We report ^2^3^8U/^2^3^5U ratios of five angrites and give the corresponding Pb-Pb ages of D'Orbigny and Angra Dos Reis. The U-isotopic composition of terrestrial granites (I, S, and A types) is also assessed to determine the influence of the protolith.

MSH3 polymorphisms and protein levels affect CAG repeat instability in Huntington's disease mice.

PubMed

Tomé, Stéphanie; Manley, Kevin; Simard, Jodie P; Clark, Greg W; Slean, Meghan M; Swami, Meera; Shelbourne, Peggy F; Tillier, Elisabeth R M; Monckton, Darren G; Messer, Anne; Pearson, Christopher E

2013-01-01

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)∼100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of

MSH3 Polymorphisms and Protein Levels Affect CAG Repeat Instability in Huntington's Disease Mice

PubMed Central

Simard, Jodie P.; Clark, Greg W.; Slean, Meghan M.; Swami, Meera; Shelbourne, Peggy F.; Tillier, Elisabeth R. M.; Monckton, Darren G.; Messer, Anne; Pearson, Christopher E.

2013-01-01

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)∼100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of

Crosstalk between MSH2–MSH3 and polβ promotes trinucleotide repeat expansion during base excision repair

PubMed Central

Lai, Yanhao; Budworth, Helen; Beaver, Jill M.; Chan, Nelson L. S.; Zhang, Zunzhen; McMurray, Cynthia T.; Liu, Yuan

2016-01-01

Studies in knockout mice provide evidence that MSH2–MSH3 and the BER machinery promote trinucleotide repeat (TNR) expansion, yet how these two different repair pathways cause the mutation is unknown. Here we report the first molecular crosstalk mechanism, in which MSH2–MSH3 is used as a component of the BER machinery to cause expansion. On its own, pol β fails to copy TNRs during DNA synthesis, and bypasses them on the template strand to cause deletion. Remarkably, MSH2–MSH3 not only stimulates pol β to copy through the repeats but also enhances formation of the flap precursor for expansion. Our results provide direct evidence that MMR and BER, operating together, form a novel hybrid pathway that changes the outcome of TNR instability from deletion to expansion during the removal of oxidized bases. We propose that cells implement crosstalk strategies and share machinery when a canonical pathway is ineffective in removing a difficult lesion. PMID:27546332

Age-related differences in repeated-sprint ability in highly trained youth football players.

PubMed

Mujika, Inigo; Spencer, Matt; Santisteban, Juanma; Goiriena, Juan Jose; Bishop, David

2009-12-01

In this study, we investigated the age-related differences in repeated-sprint ability and blood lactate responses in 134 youth football players. Players from the development programme of a professional club were grouped according to their respective under-age team (U-11 to U-18). Following familiarization, the participants performed a repeated-sprint ability test [6 x 30-m sprints 30 s apart, with active recovery (2.0-2.2 m . s(-1)) between sprints]. The test variables were total time, percent sprint decrement, and post-test peak lactate concentration. Total time improved from the U-11 to U-15 age groups (range 33.15 +/- 1.84 vs. 27.25 +/- 0.82 s), whereas no further significant improvements were evident from U-15 to U-18. No significant differences in percent sprint decrement were reported among groups (range 4.0 +/- 1.0% to 5.5 +/- 2.1%). Post-test peak lactate increased from one age group to the next (range 7.3 +/- 1.8 to 12.6 +/- 1.6 mmol . l(-1)), but remained constant when adjusted for age-related difference in body mass. Peak lactate concentration was moderately correlated with sprint time (r = 0.70, P > 0.001). Our results suggest that performance in repeated-sprint ability improves during maturation of highly trained youth football players, although a plateau occurs from 15 years of age. In contrast to expectations based on previous suggestions, percent sprint decrement during repeated sprints did not deteriorate with age.

[Clinical values of single or repeated triptorelin stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism and constitutional delayed puberty].

PubMed

Mao, Jiang-Feng; Wu, Xue-Yan; Lu, Shuang-Yu; Nie, Min

2011-10-01

To investigate the values of single or repeated luteinizing hormone (LH) releasing hormone analogue (triptorelin) stimulating test in the differential diagnosis between idiopathic hypogonadotropic hypogonadism (IHH) and constitutional delayed puberty (CDP). Male patients (n = 133) without puberty onset after the age of 14 were recruited for triptorelin stimulating test and were followed up for 24 - 48 months until the diagnosis were confirmed: 86 were IHH and the other 47 were CDP. Repeated triptorelin stimulating tests were conducted in 9 IHH patients and 13 CDP patients one year after the first stimulating tests with an attempt to evaluate the dynamic change of hypothalamus-pituitary-testis axis function. The relationship between the final diagnosis and the peak LH value (LH(max)), and the changes of repeated LH(max) were investigated. In the single triptorelin stimulating test, LH(max) was (1.9 +/- 1.2) U/L in IHH group, which was significantly lower than that in CDP group [(13.7 +/- 8.3) U/L] (P < 0.01); 75 IHH patients (87.2%) had a LH(max) lower than 4 U/L, while only 2 CDP patients (4.3%) had a LH(max) lower than 4 U/L. When LH(max) < 4U/L was used as a criteria for the diagnosis of IHH, the single triptorelin stimulating test had a sensitivity of 87.2%, a specificity of 95.7%, and a positive predictive value of 97.4%. The repeated triptorelin stimulating tests performed one year later showed that the LH(max) in the 9 IHH patients increased from (4.7 +/- 2.5) U/L to (5.1 +/- 3.3) U/L (P = 0.78), while that in the 13 CDP patients increased from (10.7 +/- 3.3) U/L to (24.5 +/- 5.7) U/L (P < 0.05). A single triptorelin stimulating test is highly effective in differentiating IHH from CDP. For some patients without definitive diagnosis, a repeated triptorelin stimulating test performed one year later may provide more valuable information on the dynamic change of the hypothalamus-pituitary-testis axis function.

Integral cross sections for the direct excitation of the A 3 (sigma) u +, B 3 (pi) g, W 3 (delta) u, B' 3 (sigma) u -, a' 1 (sigma) u -, a 1 (pi) g, w 1 (delta) u, and C 3 (pi) u electronic states in

NASA Technical Reports Server (NTRS)

Johnson, P. V.; Malone, C. P.; Kanik, I.

2005-01-01

Integral cross sections for electron impact excitation out of the ground state (X 1(sigma)g +) to the A 3(sigma)u +, B 3(pi)g, W 3(delta)u, B' 3(sigma)u -, a' 1(sigma)u -, a 1(pi)g, w 1(delta)u, and states in N2 are reported at incident energies ranging between 10 and 100 eV. These data have been derived by integrating differential cross sections previously reported by this group. New differential cross section measurements for the a 1(pi)g state at 200 eV are also presented to extend the range of the reported integral cross sections for this state, which is responsible for the emissions of the Lyman-Birge-Hopfield band system (a 1(pi)g (rightwards arrow) X 1(sigma)g +). The present results are compared and critically evaluated against existing cross sec In general, the present cross sections are smaller than previous results at low impact energies from threshold through the excitation function peak regions. These lower cross sections have potentially significant implications on our understanding of UV emissions in the atmospheres of Earth and Titan.

A Contribution to the Kinetic Study of the Metatectic Reaction U+U$sub 3$Si$sub 2$$Yields$U$sub 3$Si; CONTRIBUTION AL ESTUDIO CINETICO DE LA REACCION METATECTICA U+U$sub 3$Si$sub 2$$Yields$U$sub 3$Si

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

Ruiperez, J.A.; Hernandez, J.A.E.

1962-01-01

An experimental study was made to decide upon the advantages and drawbacks of the different methods and reagents employed in the metallography of U-Si alloys. It has been observed that all samples thermally treated to the epsilon-phase undergo a coalescence of the U/sub 3/Si/sub 2/ particles. The coalescence decreases the surface available for reaction and consequently the reaction rate. The growth of the U/sub 3/Si/sub 2/ phase particles was determined as a function of time and temperature. To obtain samples with nuclei sufficiently isolated so that the U/sub 3/Si rings will not interfere their respective growth, the conditions that regulatemore » coalescence, Si content and thermal treatment, were determined. Data rel1tive to the growth of the U/sub 3/ Si phase-rings were obtained. Curves relating growth, time, and temperature are presented. The parameters that define the diffusion regulated reaction can be deduced from these curves. (auth)« less

Cognitive enhancement and antipsychotic-like activity following repeated dosing with the selective M4 PAM VU0467154.

PubMed

Gould, Robert W; Grannan, Michael D; Gunter, Barak W; Ball, Jacob; Bubser, Michael; Bridges, Thomas M; Wess, Jurgen; Wood, Michael W; Brandon, Nicholas J; Duggan, Mark E; Niswender, Colleen M; Lindsley, Craig W; Conn, P Jeffrey; Jones, Carrie K

2018-01-01

Although selective activation of the M 1 muscarinic acetylcholine receptor (mAChR) subtype has been shown to improve cognitive function in animal models of neuropsychiatric disorders, recent evidence suggests that enhancing M 4 mAChR function can also improve memory performance. Positive allosteric modulators (PAMs) targeting the M 4 mAChR subtype have shown therapeutic potential for the treatment of multiple symptoms observed in schizophrenia, including positive and cognitive symptoms when assessed in acute preclinical dosing paradigms. Since the cholinergic system has been implicated in multiple stages of learning and memory, we evaluated the effects of repeated dosing with the highly selective M 4 PAM VU0467154 on either acquisition and/or consolidation of learning and memory when dosed alone or after pharmacologic challenge with the N-methyl-d-aspartate subtype of glutamate receptors (NMDAR) antagonist MK-801. MK-801 challenge represents a well-documented preclinical model of NMDAR hypofunction that is thought to underlie some of the positive and cognitive symptoms observed in schizophrenia. In wildtype mice, 10-day, once-daily dosing of VU0467154 either prior to, or immediately after daily testing enhanced the rate of learning in a touchscreen visual pairwise discrimination task; these effects were absent in M 4 mAChR knockout mice. Following a similar 10-day, once-daily dosing regimen of VU0467154, we also observed 1) improved acquisition of memory in a cue-mediated conditioned freezing paradigm, 2) attenuation of MK-801-induced disruptions in the acquisition of memory in a context-mediated conditioned freezing paradigm and 3) reversal of MK-801-induced hyperlocomotion. Comparable efficacy and plasma and brain concentrations of VU0467154 were observed after repeated dosing as those previously reported with an acute, single dose administration of this M 4 PAM. Together, these studies are the first to demonstrate that cognitive enhancing and antipsychotic

Enhanced Access to the Dark Triplet States of 7Li 2 through New Singlet-Triplet A1Σ +u ˜ b3Π u Perturbation Window Levels: Perturbation-Facilitated Optical-Optical Double Resonance Study of the 2 3Σ +g State

NASA Astrophysics Data System (ADS)

Lazarov, Guenadiy; Lyyra, A. Marjatta; Li, Li

2001-01-01

Two new pairs of singlet-triplet A1Σ+u ∼ b3Πu mixed levels of 7Li2 have been observed and used here as 'window' levels in cw perturbation-facilitated optical-optical double-resonance (PFOODR) experiments. Previously, only one b3Πu vibrational level, v = 19, was known to mix with the singlet A1Σ+uv = 13 level, resulting in three perturbed A ∼ b pairs [L. Li, T. An, T.-J. Whang, A. M. Lyyra, W. C. Stwalley, R. W. Field, and R. A. Bernheim, J. Chem. Phys. 96, 3342 (1992)]. The scarcity of window levels and the resulting difficulty in accessing the dark triplet states of Li2 is caused by the weak spin-orbit interaction of Li2. The two new mixed b3Πuv = 15 and 22 levels reported here enhance access to the dark triplet state manifold through expansion of the Franck-Condon overlap factor range. Furthermore, the earlier range of accessible rotational levels, N = 5, 7, and 10, is now expanded to include N = 8 and N = 16, thereby allowing for more reliable determination of the excited triplet states rotational structure. To demonstrate the importance of the new A1Σ+u ∼ b3Πu mixed levels, we have studied the 23Σ+g state by cw PFOODR fluorescence excitation spectroscopy. New molecular constants and RKR potential curve have been determined. As previously reported [L. Li, G. Lazarov, and A. M. Lyyra, J. Mol. Spectrosc. 191, 387 (1998)], the 23Σ+g state interacts with the repulsive 13Πg state by L-uncoupling and predissociates. We show that some 23Πg levels predissociate accidentally by the 13Πg state via the 23Σ+g state through L-uncoupling.

The effect of aluminum additions on the oxidation resistance of U 3Si 2

DOE PAGES

Wood, E. Sooby; White, J. T.; Nelson, A. T.

2017-04-01

The effect of aluminum additions to U 3Si 2 is investigated in this paper as a means to improve the oxidation resistance of this nuclear fuel form. Four U-Si-Al compositions have been synthesized and characterized using scanning electron microscopy, energy dispersive spectroscopy, and x-ray diffraction. The onsets of breakaway oxidation are identified in air thermal ramp tests using thermogravimetric analysis. The final oxidation products following 1000° C air exposure are identified using x-ray diffraction and compared to those of UO 2 and U metal oxidized in the same manner. Finally, thermogravimetric data acquired in this study indicates that increasing amountsmore » of Al in U 3Si 2 further delays the onset of breakaway oxidation, providing enhanced oxidation resistance in air. Al 2O 3 formation on U 3Al 2Si 3 is observed following a heat treatment performed at 500° C in air, demonstrating the potential of Al additions to improve the oxidation resistance of U 3Si 2.« less

The effect of aluminum additions on the oxidation resistance of U 3Si 2

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

Wood, E. Sooby; White, J. T.; Nelson, A. T.

The effect of aluminum additions to U 3Si 2 is investigated in this paper as a means to improve the oxidation resistance of this nuclear fuel form. Four U-Si-Al compositions have been synthesized and characterized using scanning electron microscopy, energy dispersive spectroscopy, and x-ray diffraction. The onsets of breakaway oxidation are identified in air thermal ramp tests using thermogravimetric analysis. The final oxidation products following 1000° C air exposure are identified using x-ray diffraction and compared to those of UO 2 and U metal oxidized in the same manner. Finally, thermogravimetric data acquired in this study indicates that increasing amountsmore » of Al in U 3Si 2 further delays the onset of breakaway oxidation, providing enhanced oxidation resistance in air. Al 2O 3 formation on U 3Al 2Si 3 is observed following a heat treatment performed at 500° C in air, demonstrating the potential of Al additions to improve the oxidation resistance of U 3Si 2.« less

β4-integrin-mediated cytotoxic activity of AexU in human prostate cancer PC3 cells

PubMed Central

KUMANO, MASAFUMI; MIYAKE, HIDEAKI; ABOLGHAIT, SAID K.; BEHNSAWY, HOSNY M.; FUJISAWA, MASATO

2013-01-01

The present study aimed to characterize the cytotoxic activity of AexU, an effector-mediating type three secretion system (TTSS) of gram-negative bacteria, in human prostate cancer cells, focusing on the association with β4-integrin expression. The cytotoxic effects of AexU either alone or in combination with chemotherapeutic agents were evaluated using several human prostate cancer cell lines. Human prostate cancer PC3 cells, in which an expression vector containing siRNA targeting β4-integrin had been introduced, were established (PC3/sh-In), and the cytotoxic effects of AexU on the PC3/sh-In cells were compared with the PC3 cells that were transfected with a control vector (PC3/C). The expression levels of β4-integrin in the PC3 cells were markedly higher compared with those in the LNCaP or DU145 cells, and the cytotoxic effects of AexU in the PC3 cells were more pronounced compared with those in the LNCaP or DU145 cells. The sensitivity of the PC3 cells to docetaxel and cisplatin was significantly enhanced following treatment with AexU, resulting in a decrease in the IC50 of the two agents by ~90%. The cytotoxic effect of AexU in the PC3/C cells was more marked compared with that in the PC3/sh-In cells, and the phosphorylation of Akt in the PC3/C cells appeared to be significantly more inhibited by the treatment with AexU compared with the PC3/sh-In cells. In conclusion, treatment with AexU may be a useful therapeutic option for prostate cancer when β4-integrin is overexpressed. The treatment appears to exert its effects through growth inhibition and by enhancing the sensitivity of the cancer cells to chemotherapeutic agents. PMID:24179545

Time-lapse seismic - repeatability versus usefulness and 2D versus 3D

NASA Astrophysics Data System (ADS)

Landro, M.

2017-12-01

Time-lapse seismic has developed rapidly over the past decades, especially for monitoring of oil and gas reservoirs and subsurface storage of CO2. I will review and discuss some of the critical enabling factors for the commercial success of this technology. It was early realized that how well we are able to repeat our seismic experiment is crucial. However, it is always a question of detectability versus repeatability. For marine seismic, there are several factors limiting the repeatability: Weather conditions, positioning of sources and receivers and so on. I will discuss recent improvements in both acquisition and processing methods over the last decade. It is well known that repeated 3D seismic data is the most accurate tool for reservoir monitoring purposes. However, several examples show that 2D seismic data may be used for monitoring purposes despite lower repeatability. I will use examples from an underground blow out in the North Sea, and repeated 2D seismic lines acquired before and after the Tohoku earthquake in 2011 to illustrate this. A major challenge when using repeated 2D seismic for subsurface monitoring purposes is the lack of 3D calibration points and significantly less amount of data. For marine seismic acquisition, feathering issues and crossline dip effects become more critical compared to 3D seismic acquisition. Furthermore, the uncertainties arising from a non-ideal 2D seismic acquisition are hard to assess, since the 3D subsurface geometry has not been mapped. One way to shed more light on this challenge is to use 3D time lapse seismic modeling testing various crossline dips or geometries. Other ways are to use alternative data sources, such as bathymetry, time lapse gravity or electromagnetic data. The end result for all time-lapse monitoring projects is an interpretation associated with uncertainties, and for the 2D case these uncertainties are often large. The purpose of this talk is to discuss how to reduces and control these

Short-term repeated corticosterone administration enhances glutamatergic but not GABAergic transmission in the rat motor cortex.

PubMed

Kula, Joanna; Blasiak, Anna; Czerw, Anna; Tylko, Grzegorz; Sowa, Joanna; Hess, Grzegorz

2016-04-01

It has been demonstrated that stress impairs performance of skilled reaching and walking tasks in rats due to the action of glucocorticoids involved in the stress response. Skilled reaching and walking are controlled by the primary motor cortex (M1); however, it is not known whether stress-related impairments in skilled motor tasks are related to functional and/or structural alterations within the M1. We studied the effects of single and repeated injections of corticosterone (twice daily for 7 days) on spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) recorded from layer II/III pyramidal neurons in ex vivo slices of the M1, prepared 2 days after the last administration of the hormone. We also measured the density of dendritic spines on pyramidal cells and the protein levels of selected subunits of AMPA, NMDA, and GABAA receptors after repeated corticosterone administration. Repeatedly administered corticosterone induced an increase in the frequency but not in the amplitude of sEPSCs, while a single administration had no effect on the recorded excitatory currents. The frequency and amplitude of sIPSCs as well as the excitability of pyramidal cells were changed neither after single nor after repeated corticosterone administration. Treatment with corticosterone for 7 days did not modify the density of dendritic spines on pyramidal neurons. Corticosterone influenced neither the protein levels of GluA1, GluA2, GluN1, GluN2A, and GluN2B subunits of glutamate receptors nor those of α1, β2, and γ2 subunits of the GABAA receptor. The increase in sEPSCs frequency induced by repeated corticosterone administration faded out within 7 days. These data indicate that prolonged administration of exogenous corticosterone selectively and reversibly enhances glutamatergic, but not GABAergic transmission in the rat motor cortex. Our results suggest that corticosterone treatment results in an enhancement of spontaneous glutamate release from presynaptic

3'-UTR-located inverted Alu repeats facilitate mRNA translational repression and stress granule accumulation

PubMed Central

Fitzpatrick, Terry; Huang, Sui

2012-01-01

Alu repeats within human genes may potentially alter gene expression. Here, we show that 3′-UTR-located inverted Alu repeats significantly reduce expression of an AcGFP reporter gene. Mutational analysis demonstrates that the secondary structure, but not the primary nucleotide sequence, of the inverted Alu repeats is critical for repression. The expression levels and nucleocytoplasmic distribution of reporter mRNAs with or without 3′-UTR inverted Alu repeats are similar; suggesting that reporter gene repression is not due to changes in mRNA levels or mRNA nuclear sequestration. Instead, reporter gene mRNAs harboring 3′-UTR inverted Alu repeats accumulate in cytoplasmic stress granules. These findings may suggest a novel mechanism whereby 3′-UTR-located inverted Alu repeats regulate human gene expression through sequestration of mRNAs within stress granules. PMID:22688648

Schizosaccharomyces pombe MutSα and MutLα Maintain Stability of Tetra-Nucleotide Repeats and Msh3 of Hepta-Nucleotide Repeats

PubMed Central

Villahermosa, Desirée; Christensen, Olaf; Knapp, Karen; Fleck, Oliver

2017-01-01

Defective mismatch repair (MMR) in humans is associated with colon cancer and instability of microsatellites, that is, DNA sequences with one or several nucleotides repeated. Key factors of eukaryotic MMR are the heterodimers MutSα (Msh2-Msh6), which recognizes base-base mismatches and unpaired nucleotides in DNA, and MutLα (Mlh1-Pms1), which facilitates downstream steps. In addition, MutSβ (Msh2-Msh3) recognizes DNA loops of various sizes, although our previous data and the data presented here suggest that Msh3 of Schizosaccharomyces pombe does not play a role in MMR. To test microsatellite stability in S. pombe and hence DNA loop repair, we have inserted tetra-, penta-, and hepta-nucleotide repeats in the ade6 gene and determined their Ade+ reversion rates and spectra in wild type and various mutants. Our data indicate that loops with four unpaired nucleotides in the nascent and the template strand are the upper limit of MutSα- and MutLα-mediated MMR in S. pombe. Stability of hepta-nucleotide repeats requires Msh3 and Exo1 in MMR-independent processes as well as the DNA repair proteins Rad50, Rad51, and Rad2FEN1. Most strikingly, mutation rates in the double mutants msh3 exo1 and msh3 rad51 were decreased when compared to respective single mutants, indicating that Msh3 prevents error prone processes carried out by Exo1 and Rad51. We conclude that Msh3 has no obvious function in MMR in S. pombe, but contributes to DNA repeat stability in MMR-independent processes. PMID:28341698

Schizosaccharomyces pombe MutSα and MutLα Maintain Stability of Tetra-Nucleotide Repeats and Msh3 of Hepta-Nucleotide Repeats.

PubMed

Villahermosa, Desirée; Christensen, Olaf; Knapp, Karen; Fleck, Oliver

2017-05-05

Defective mismatch repair (MMR) in humans is associated with colon cancer and instability of microsatellites, that is, DNA sequences with one or several nucleotides repeated. Key factors of eukaryotic MMR are the heterodimers MutSα (Msh2-Msh6), which recognizes base-base mismatches and unpaired nucleotides in DNA, and MutLα (Mlh1-Pms1), which facilitates downstream steps. In addition, MutSβ (Msh2-Msh3) recognizes DNA loops of various sizes, although our previous data and the data presented here suggest that Msh3 of Schizosaccharomyces pombe does not play a role in MMR. To test microsatellite stability in S. pombe and hence DNA loop repair, we have inserted tetra-, penta-, and hepta-nucleotide repeats in the ade6 gene and determined their Ade + reversion rates and spectra in wild type and various mutants. Our data indicate that loops with four unpaired nucleotides in the nascent and the template strand are the upper limit of MutSα- and MutLα-mediated MMR in S. pombe Stability of hepta-nucleotide repeats requires Msh3 and Exo1 in MMR-independent processes as well as the DNA repair proteins Rad50, Rad51, and Rad2 FEN1 Most strikingly, mutation rates in the double mutants msh3 exo1 and msh3 rad51 were decreased when compared to respective single mutants, indicating that Msh3 prevents error prone processes carried out by Exo1 and Rad51. We conclude that Msh3 has no obvious function in MMR in S. pombe , but contributes to DNA repeat stability in MMR-independent processes. Copyright © 2017 Villahermosa et al.

Improving cellulase productivity of Penicillium oxalicum RE-10 by repeated fed-batch fermentation strategy.

PubMed

Han, Xiaolong; Song, Wenxia; Liu, Guodong; Li, Zhonghai; Yang, Piao; Qu, Yinbo

2017-03-01

Medium optimization and repeated fed-batch fermentation were performed to improve the cellulase productivity by P. oxalicum RE-10 in submerged fermentation. First, Plackett-Burman design (PBD) and central composite design (CCD) were used to optimize the medium for cellulase production. PBD demonstrated wheat bran and NaNO 3 had significant influences on cellulase production. The CCD results showed the maximum filter paper activity (FPA) production of 8.61U/mL could be achieved in Erlenmeyer flasks. The maximal FPA reached 12.69U/mL by submerged batch fermentation in a 7.5-L stirred tank, 1.76-fold higher than that on the original medium. Then, the repeated fed-batch fermentation strategy was performed successfully for increasing the cellulase productivity from 105.75U/L/h in batch fermentation to 158.38U/L/h. The cellulase activity and the glucan conversion of delignined corn cob residue hydrolysis had no significant difference between the enzymes sampled from different cycles of the repeated fed-batch fermentation and that from batch culture. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ingestion of High Molecular Weight Carbohydrate Enhances Subsequent Repeated Maximal Power: A Randomized Controlled Trial

PubMed Central

Oliver, Jonathan M.; Almada, Anthony L.; Van Eck, Leighsa E.; Shah, Meena; Mitchell, Joel B.; Jones, Margaret T.; Jagim, Andrew R.; Rowlands, David S.

2016-01-01

Athletes in sports demanding repeat maximal work outputs frequently train concurrently utilizing sequential bouts of intense endurance and resistance training sessions. On a daily basis, maximal work within subsequent bouts may be limited by muscle glycogen availability. Recently, the ingestion of a unique high molecular weight (HMW) carbohydrate was found to increase glycogen re-synthesis rate and enhance work output during subsequent endurance exercise, relative to low molecular weight (LMW) carbohydrate ingestion. The effect of the HMW carbohydrate, however, on the performance of intense resistance exercise following prolonged-intense endurance training is unknown. Sixteen resistance trained men (23±3 years; 176.7±9.8 cm; 88.2±8.6 kg) participated in a double-blind, placebo-controlled, randomized 3-way crossover design comprising a muscle-glycogen depleting cycling exercise followed by ingestion of placebo (PLA), or 1.2 g•kg•bw-1 of LMW or HMW carbohydrate solution (10%) with blood sampling for 2-h post-ingestion. Thereafter, participants performed 5 sets of 10 maximal explosive repetitions of back squat (75% of 1RM). Compared to PLA, ingestion of HMW (4.9%, 90%CI 3.8%, 5.9%) and LMW (1.9%, 90%CI 0.8%, 3.0%) carbohydrate solutions substantially increased power output during resistance exercise, with the 3.1% (90% CI 4.3, 2.0%) almost certain additional gain in power after HMW-LMW ingestion attributed to higher movement velocity after force kinematic analysis (HMW-LMW 2.5%, 90%CI 1.4, 3.7%). Both carbohydrate solutions increased post-exercise plasma glucose, glucoregulatory and gut hormones compared to PLA, but differences between carbohydrates were unclear; thus, the underlying mechanism remains to be elucidated. Ingestion of a HMW carbohydrate following prolonged intense endurance exercise provides superior benefits to movement velocity and power output during subsequent repeated maximal explosive resistance exercise. This study was registered with

Ingestion of High Molecular Weight Carbohydrate Enhances Subsequent Repeated Maximal Power: A Randomized Controlled Trial.

PubMed

Oliver, Jonathan M; Almada, Anthony L; Van Eck, Leighsa E; Shah, Meena; Mitchell, Joel B; Jones, Margaret T; Jagim, Andrew R; Rowlands, David S

2016-01-01

Athletes in sports demanding repeat maximal work outputs frequently train concurrently utilizing sequential bouts of intense endurance and resistance training sessions. On a daily basis, maximal work within subsequent bouts may be limited by muscle glycogen availability. Recently, the ingestion of a unique high molecular weight (HMW) carbohydrate was found to increase glycogen re-synthesis rate and enhance work output during subsequent endurance exercise, relative to low molecular weight (LMW) carbohydrate ingestion. The effect of the HMW carbohydrate, however, on the performance of intense resistance exercise following prolonged-intense endurance training is unknown. Sixteen resistance trained men (23±3 years; 176.7±9.8 cm; 88.2±8.6 kg) participated in a double-blind, placebo-controlled, randomized 3-way crossover design comprising a muscle-glycogen depleting cycling exercise followed by ingestion of placebo (PLA), or 1.2 g•kg•bw-1 of LMW or HMW carbohydrate solution (10%) with blood sampling for 2-h post-ingestion. Thereafter, participants performed 5 sets of 10 maximal explosive repetitions of back squat (75% of 1RM). Compared to PLA, ingestion of HMW (4.9%, 90%CI 3.8%, 5.9%) and LMW (1.9%, 90%CI 0.8%, 3.0%) carbohydrate solutions substantially increased power output during resistance exercise, with the 3.1% (90% CI 4.3, 2.0%) almost certain additional gain in power after HMW-LMW ingestion attributed to higher movement velocity after force kinematic analysis (HMW-LMW 2.5%, 90%CI 1.4, 3.7%). Both carbohydrate solutions increased post-exercise plasma glucose, glucoregulatory and gut hormones compared to PLA, but differences between carbohydrates were unclear; thus, the underlying mechanism remains to be elucidated. Ingestion of a HMW carbohydrate following prolonged intense endurance exercise provides superior benefits to movement velocity and power output during subsequent repeated maximal explosive resistance exercise. This study was registered with

Facile synthesis of magnetic Fe3O4/graphene composites for enhanced U(VI) sorption

NASA Astrophysics Data System (ADS)

Zhao, Donglin; Zhu, Hongyu; Wu, Changnian; Feng, Shaojie; Alsaedi, Ahmed; Hayat, Tasawar; Chen, Changlun

2018-06-01

A novel magnetic Fe3O4/graphene composite (FGC) was fabricated by a facile one-step reaction route and shown to be effective for sorbing U(VI) from aqueous solution. The structure, properties and application of the prepared FGC composite were well evaluated. The high saturation magnetization (45.6 emu/g) made FGC easier to be separated from the media within several seconds under an external magnetic. Effects of different ambient conditions (i.e., pH and ionic strength, contact time, temperatures) on sorption behaviors of U(VI) on FGC were carried out by batch experiments. According to the calculation of Langmuir model, the maximum sorption capacity of U(VI) on the FGC at pH 5.5 and 298 K was 176.47 mg/g. The sorption was correlated with the effects of pH, contact time, and temperature. X-ray photoelectron spectroscopy analysis revealed that U(VI) was sorbed on FGC via oxygen-containing functional groups. This work demonstrated that FGC could be recycled and used as an effective recyclable sorbent for sorption of U(VI).

Evidence that C9ORF72 Dipeptide Repeat Proteins Associate with U2 snRNP to Cause Mis-splicing in ALS/FTD Patients.

PubMed

Yin, Shanye; Lopez-Gonzalez, Rodrigo; Kunz, Ryan C; Gangopadhyay, Jaya; Borufka, Carl; Gygi, Steven P; Gao, Fen-Biao; Reed, Robin

2017-06-13

Hexanucleotide repeat expansion in the C9ORF72 gene results in production of dipeptide repeat (DPR) proteins that may disrupt pre-mRNA splicing in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients. At present, the mechanisms underlying this mis-splicing are not understood. Here, we show that addition of proline-arginine (PR) and glycine-arginine (GR) toxic DPR peptides to nuclear extracts blocks spliceosome assembly and splicing, but not other types of RNA processing. Proteomic and biochemical analyses identified the U2 small nuclear ribonucleoprotein particle (snRNP) as a major interactor of PR and GR peptides. In addition, U2 snRNP, but not other splicing factors, mislocalizes from the nucleus to the cytoplasm both in C9ORF72 patient induced pluripotent stem cell (iPSC)-derived motor neurons and in HeLa cells treated with the toxic peptides. Bioinformatic studies support a specific role for U2-snRNP-dependent mis-splicing in C9ORF72 patient brains. Together, our data indicate that DPR-mediated dysfunction of U2 snRNP could account for as much as ∼44% of the mis-spliced cassette exons in C9ORF72 patient brains. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Interdiffusion in U 3Si-Al, U 3Si 2-Al, and USi-Al dispersion fuels during irradiation

NASA Astrophysics Data System (ADS)

Kim, Yeon Soo; Hofman, Gerard L.

2011-03-01

Uranium-silicide compound fuel dispersion in an Al matrix is used in research and test reactors worldwide. Interaction layer (IL) growth between fuel particles and the matrix is one of performance issues. The interaction layer growth data for U 3Si, U 3Si 2 and USi dispersions in Al were obtained from both out-of-pile and in-pile tests. The IL is dominantly U(AlSi) 3 from out-of-pile tests, but its (Al + Si)/U ratio from in-pile tests is higher than the out-of-pile data, because of amorphous behavior of the ILs. IL growth correlations were developed for U 3Si-Al and U 3Si 2-Al. The IL growth rates were dependent on the U/Si ratio of the fuel compounds. During irradiation, however, the IL growth rates did not decrease with the decreasing U/Si ratio by fission. It is reasoned that transition metal fission products in the IL compensate the loss of U atoms by providing chemical potential for Al diffusion and volume expansion by solid swelling and gas bubble swelling. The addition of Mo in U 3Si 2 reduces the IL growth rate, which is similar to that of UMo alloy dispersion in a silicon-added Al matrix.

A variable number of tandem repeats in the 3'-untranslated region of the dopamine transporter modulates striatal function during working memory updating across the adult age span.

PubMed

Sambataro, Fabio; Podell, Jamie E; Murty, Vishnu P; Das, Saumitra; Kolachana, Bhaskar; Goldberg, Terry E; Weinberger, Daniel R; Mattay, Venkata S

2015-08-01

Dopamine modulation of striatal function is critical for executive functions such as working memory (WM) updating. The dopamine transporter (DAT) regulates striatal dopamine signaling via synaptic reuptake. A variable number of tandem repeats in the 3'-untranslated region of SLC6A3 (DAT1-3'-UTR-VNTR) is associated with DAT expression, such that 9-repeat allele carriers tend to express lower levels (associated with higher extracellular dopamine concentrations) than 10-repeat homozygotes. Aging is also associated with decline of the dopamine system. The goal of the present study was to investigate the effects of aging and DAT1-3'-UTR-VNTR on the neural activity and functional connectivity of the striatum during WM updating. Our results showed both an age-related decrease in striatal activity and an effect of DAT1-3'-UTR-VNTR. Ten-repeat homozygotes showed reduced striatal activity and increased striatal-hippocampal connectivity during WM updating relative to the 9-repeat carriers. There was no age by DAT1-3'-UTR-VNTR interaction. These results suggest that, whereas striatal function during WM updating is modulated by both age and genetically determined DAT levels, the rate of the age-related decline in striatal function is similar across both DAT1-3'-UTR-VNTR genotype groups. They further suggest that, because of the baseline difference in striatal function based on DAT1-3'-UTR-VNTR polymorphism, 10-repeat homozygotes, who have lower levels of striatal function throughout the adult life span, may reach a threshold of decreased striatal function and manifest impairments in cognitive processes mediated by the striatum earlier in life than the 9-repeat carriers. Our data suggest that age and DAT1-3'-UTR-VNTR polymorphism independently modulate striatal function. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

F8U-3 aircraft

NASA Image and Video Library

1959-09-10

Crusader on runway. Navy aircraft number 6340. L59-6101 caption: The Navy's Vought XF8U-3 Supersonic Fighter was an entirely new design as compared to the earlier F8U Crusader series. This jet plane lost in competition with the McDonnell F4H, however, and was never put into production. Langley used the XF8U-3 in some of the first flight measurements of sonic boom intensity. Photograph published in Engineer in Charge A History of the Langley Aeronautical Laboratory, 1917-1958 by James R. Hansen. Page 507. Caption: Chance Vought F8U-3 airplane used in sonic boom investigation at Wallops, June-August 1959. Photograph published in A New Dimension Wallops Island Flight Test Range: The First Fifteen Years by Joseph Shortal. A NASA publication. Page 672.

Grain Size and Phase Purity Characterization of U 3Si 2 Pellet Fuel

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

Hoggan, Rita E.; Tolman, Kevin R.; Cappia, Fabiola

Characterization of U 3Si 2 fresh fuel pellets is important for quality assurance and validation of the finished product. Grain size measurement methods, phase identification methods using scanning electron microscopes equipped with energy dispersive spectroscopy and x-ray diffraction, and phase quantification methods via image analysis have been developed and implemented on U 3Si 2 pellet samples. A wide variety of samples have been characterized including representative pellets from an initial irradiation experiment, and samples produced using optimized methods to enhance phase purity from an extended fabrication effort. The average grain size for initial pellets was between 16 and 18 µm.more » The typical average grain size for pellets from the extended fabrication was between 20 and 30 µm with some samples exhibiting irregular grain growth. Pellets from the latter half of extended fabrication had a bimodal grain size distribution consisting of coarsened grains (>80 µm) surrounded by the typical (20-30 µm) grain structure around the surface. Phases identified in initial uranium silicide pellets included: U 3Si 2 as the main phase composing about 80 vol. %, Si rich phases (USi and U 5Si 4) composing about 13 vol. %, and UO 2 composing about 5 vol. %. Initial batches from the extended U 3Si 2 pellet fabrication had similar phases and phase quantities. The latter half of the extended fabrication pellet batches did not contain Si rich phases, and had between 1-5% UO 2: achieving U 3Si 2 phase purity between 95 vol. % and 98 vol. % U 3Si 2. The amount of UO 2 in sintered U 3Si 2 pellets is correlated to the length of time between U 3Si 2 powder fabrication and pellet formation. These measurements provide information necessary to optimize fabrication efforts and a baseline for future work on this fuel compound.« less

Deployment Repeatability

DTIC Science & Technology

2016-04-01

environment. Modeling is suitable for well- characterized parts, and stochastic modeling techniques can be used for sensitivity analysis and generating a...large cohort of trials to spot unusual cases. However, deployment repeatability is inherently a nonlinear phenomenon, which makes modeling difficult...recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the U.S. Air Force. 1. Test the flight model

Repeated assessment of orthotopic glioma pO2 by multi-site EPR oximetry: A technique with the potential to guide therapeutic optimization by repeated measurements of oxygen

PubMed Central

Khan, Nadeem; Mupparaju, Sriram; Hou, Huagang; Williams, Benjamin B.; Swartz, Harold

2011-01-01

Tumor hypoxia plays a vital role in therapeutic resistance. Consequently, measurements of tumor pO2 could be used to optimize the outcome of oxygen-dependent therapies, such as, chemoradiation. However, the potential optimizations are restricted by the lack of methods to repeatedly and quantitatively assess tumor pO2 during therapies, particularly in gliomas. We describe the procedures for repeated measurements of orthotopic glioma pO2 by multi-site electron paramagnetic resonance (EPR) oximetry. This oximetry approach provides simultaneous measurements of pO2 at more than one site in the glioma and contralateral cerebral tissue. The pO2 of intracerebral 9L, C6, F98 and U251 tumors, as well as contralateral brain, were measured repeatedly for five consecutive days. The 9L glioma was well oxygenated with pO2 of 27 - 36 mm Hg, while C6, F98 and U251 glioma were hypoxic with pO2 of 7 - 12 mm Hg. The potential of multi-site EPR oximetry to assess temporal changes in tissue pO2 was investigated in rats breathing 100% O2. A significant increase in F98 tumor and contralateral brain pO2 was observed on day 1 and day 2, however, glioma oxygenation declined on subsequent days. In conclusion, EPR oximetry provides the capability to repeatedly assess temporal changes in orthotopic glioma pO2. This information could be used to test and optimize the methods being developed to modulate tumor hypoxia. Furthermore, EPR oximetry could be potentially used to enhance the outcome of chemoradiation by scheduling treatments at times of increase in glioma pO2. PMID:22079559

Magnetotransport and Heat Capacity in Ternary Compounds U3M2M‧3‧, M=Al, Ga; M=Si, Ge

NASA Astrophysics Data System (ADS)

Troć, R.; Rogl, P.; Tran, V. H.; Czopnik, A.

2001-05-01

We report detailed studies of magnetization, electrical resistivity, magnetoresistivity, and heat capacity performed on the novel family of intermetallic compounds U3M2M‧3, (M=Al, Ga, and M‧=Si, Ge). The present measurements support the earlier conclusions about the ferrimagnetic properties of silicides and ferromagnetic properties of germanides. The resistivity for both compounds U3{Al,Ga}2Si3 exhibits below TC a pronounced maximum observed for the first time in an actinoid-ferrimagnet, probably caused by (a) the reduction of the number of effective conduction carriers or (b) a SDW-type of spin-disorder scattering of electrons. Both low-temperature resistivity (except for U3Ga2Si3) and heat capacity may be described by a T-dependence involving a small gap Δ on the order of 30-50 K in the magnon dispersion. The Cp/T values at 2 K are enhanced and point to a medium-heavy fermion character of all these ternaries. Magnetoresistance for ferrimagnetic U3{Al,Ga}2Si3 is rather small but positive in correspondence of antiferromagnetic interactions. In correspondence to the ferromagnetic materials, negative magnetoresistance is encountered for U3{Al,Ga}2Ge3. Specific features in the temperature dependence of magnetoresistivity Δρ/ρ at various fields confirm the sinusoidal modulation of the magnetic structure for U3Al2Ge3 between 40 and 60 K. Also, such data for U3Ga2Ge3 present strong indications for a similar magnetic modulation between 63 and 93 K, yet to be discovered by neutron diffraction experiments. In addition, the transition at 63 K is furthermore well resolved in the specific heat data of U3Ga2Ge3.

Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration.

PubMed

Convertino, V A

2001-04-01

The purpose of this study was to test the hypothesis that repeated exposure to high acceleration (G) would be associated with enhanced functions of specific mechanisms of blood pressure regulation. We measured heart rate (HR), stroke volume (SV), cardiac output (), mean arterial blood pressure, central venous pressure, forearm and leg vascular resistance, catecholamines, and changes in leg volume (%DeltaLV) during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males after three training sessions on different days over a period of 5-7 days using a human centrifuge (G trained). These responses were compared with the same measurements in 10 males who were matched for height, weight, and fitness but did not undergo G training (controls). Compared with the control group, G-trained subjects demonstrated greater R-R interval response to equal carotid baroreceptor stimulation (7.3 +/- 1.2 vs. 3.9 +/- 0.4 ms/mmHg, P = 0.02), less vasoconstriction to equal low-pressure baroreceptor stimulation (-1.4 +/- 0.2 vs. -2.6 +/- 0.3 U/mmHg, P = 0.01), and higher HR (-1.2 +/- 0.2 vs. -0.5 +/- 0.1 beats. min(-1). mmHg(-1), P = 0.01) and alpha-adrenoreceptor response (32.8 +/- 3.4 vs. 19.5 +/- 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During graded LBNP, G-trained subjects had less decline in and SV, %DeltaLV, and elevation in thoracic impedance. G-trained subjects also had greater total blood (6,497 +/- 496 vs. 5,438 +/- 228 ml, P = 0.07) and erythrocyte (3,110 +/- 364 vs. 2,310 +/- 96 ml, P = 0.06) volumes. These results support the hypothesis that exposure to repeated high G is associated with increased capacities of mechanisms that underlie blood pressure regulation.

Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration

NASA Technical Reports Server (NTRS)

Convertino, V. A.

2001-01-01

The purpose of this study was to test the hypothesis that repeated exposure to high acceleration (G) would be associated with enhanced functions of specific mechanisms of blood pressure regulation. We measured heart rate (HR), stroke volume (SV), cardiac output (), mean arterial blood pressure, central venous pressure, forearm and leg vascular resistance, catecholamines, and changes in leg volume (%DeltaLV) during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males after three training sessions on different days over a period of 5-7 days using a human centrifuge (G trained). These responses were compared with the same measurements in 10 males who were matched for height, weight, and fitness but did not undergo G training (controls). Compared with the control group, G-trained subjects demonstrated greater R-R interval response to equal carotid baroreceptor stimulation (7.3 +/- 1.2 vs. 3.9 +/- 0.4 ms/mmHg, P = 0.02), less vasoconstriction to equal low-pressure baroreceptor stimulation (-1.4 +/- 0.2 vs. -2.6 +/- 0.3 U/mmHg, P = 0.01), and higher HR (-1.2 +/- 0.2 vs. -0.5 +/- 0.1 beats. min(-1). mmHg(-1), P = 0.01) and alpha-adrenoreceptor response (32.8 +/- 3.4 vs. 19.5 +/- 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During graded LBNP, G-trained subjects had less decline in and SV, %DeltaLV, and elevation in thoracic impedance. G-trained subjects also had greater total blood (6,497 +/- 496 vs. 5,438 +/- 228 ml, P = 0.07) and erythrocyte (3,110 +/- 364 vs. 2,310 +/- 96 ml, P = 0.06) volumes. These results support the hypothesis that exposure to repeated high G is associated with increased capacities of mechanisms that underlie blood pressure regulation.

Progress of the PV Technology Incubator Project Towards an Enhanced U.S. Manufacturing Base

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

Ullal, H.; Mitchell, R.; Keyes, B.

In this paper, we report on the major accomplishments of the U.S. Department of Energy's (DOE) Solar Energy Technologies Program (SETP) Photovoltaic (PV) Technology Incubator project. The Incubator project facilitates a company's transition from developing a solar cell or PV module prototype to pilot- and large-scale U.S. manufacturing. The project targets small businesses that have demonstrated proof-of-concept devices or processes in the laboratory. Their success supports U.S. Secretary of Energy Steven Chu's SunShot Initiative, which seeks to achieve PV technologies that are cost-competitive without subsidies at large scale with fossil-based energy sources by the end of this decade. The Incubatormore » Project has enhanced U.S. PV manufacturing capacity and created more than 1200 clean energy jobs, resulting in an increase in American economic competitiveness. The investment raised to date by these PV Incubator companies as a result of DOE's $ 59 million investment total nearly $ 1.3 billion.« less

High-Intensity Small-Sided Games versus Repeated Sprint Training in Junior Soccer Players.

PubMed

Eniseler, Niyazi; Şahan, Çağatay; Özcan, Ilker; Dinler, Kıvanç

2017-12-01

The aim of this study was to compare the effects of high-intensity small-sided games training (SSGT) versus repeated-sprint training (RST) on repeated-sprint ability (RSA), soccer specific endurance performance and short passing ability among junior soccer players. The junior soccer players were recruited from of a professional team (age 16.9 ± 1.1 years). The tests included the repeated-shuttle-sprint ability test (RSSAT), Yo-Yo Intermittent Recovery Test level 1 (Yo-Yo IR1) and Loughborough Soccer Passing Test (LSPT). Nineteen participants were randomly assigned to either the small-sided games training (SSGTG) (n = 10) or repeated-sprint training group (RSTG) (n = 9). Small-sided games or repeated-sprint training were added to the regular training sessions for two days of the regular practice week. The Wilcoxon signed-rank and Mann-Whitney U tests were used to examine differences in groups and training effects. A time x training group effect was found in the improvement of short-passing ability for the smallsided games training group which showed significantly better scores than the repeated-sprint training group (p ≤ 0.05). Both groups showed similar improvements in RSAdecrement (p < 0.05). Only the repeated-sprint training group improved in the Yo-Yo IR1 (p < 0.05). This study clearly shows that high-intensity small-sided games training can be used as an effective training mode to enhance both repeated sprint ability and short-passing ability.

High-Intensity Small-Sided Games versus Repeated Sprint Training in Junior Soccer Players

PubMed Central

Şahan, Çağatay; Özcan, Ilker; Dinler, Kıvanç

2017-01-01

Abstract The aim of this study was to compare the effects of high-intensity small-sided games training (SSGT) versus repeated-sprint training (RST) on repeated-sprint ability (RSA), soccer specific endurance performance and short passing ability among junior soccer players. The junior soccer players were recruited from of a professional team (age 16.9 ± 1.1 years). The tests included the repeated-shuttle-sprint ability test (RSSAT), Yo-Yo Intermittent Recovery Test level 1 (Yo-Yo IR1) and Loughborough Soccer Passing Test (LSPT). Nineteen participants were randomly assigned to either the small-sided games training (SSGTG) (n = 10) or repeated-sprint training group (RSTG) (n = 9). Small-sided games or repeated-sprint training were added to the regular training sessions for two days of the regular practice week. The Wilcoxon signed-rank and Mann-Whitney U tests were used to examine differences in groups and training effects. A time x training group effect was found in the improvement of short-passing ability for the smallsided games training group which showed significantly better scores than the repeated-sprint training group (p ≤ 0.05). Both groups showed similar improvements in RSAdecrement (p < 0.05). Only the repeated-sprint training group improved in the Yo-Yo IR1 (p < 0.05). This study clearly shows that high-intensity small-sided games training can be used as an effective training mode to enhance both repeated sprint ability and short-passing ability. PMID:29339990

Repeated cultivation: non-cell disruption extraction of astaxanthin for Haematococcus pluvialis

PubMed Central

Sun, Han; Guan, Bin; Kong, Qing; Geng, Zhaoyan; Wang, Ni

2016-01-01

The operation of cell disruption is indispensable but cost much in microalgae industry. To be simplified, two different reaction mechanisms await in the cell to respond to moderated or stressed environment. The physical and chemical changes of enzyme and turgor pressure of cell in this conversion play an important role in the enhancement of biomass and metabolites. Repeated turgor pressure (based on the structure and mechanics of cell wall) and converted enzyme system (based on photosynthesis) were used to loosen cell wall and then repeated cultivation of Haematococcus pluvialis for astaxanthin extraction was proposed. There was no significant difference of extraction yield between the broken cell (94.75 ± 3.13%) and non-broken cell (92.32 ± 3.24%) treated by the repeated cultivation. Meanwhile, fed-batch culture according to the relationship among pH and nutrient concentration was used to enhance the biomass of Haematococcus pluvialis with the dry cell weight of 1.63 ± 0.07 g/L. PMID:26838183

Repeated restraint stress enhances cue-elicited conditioned freezing and impairs acquisition of extinction in an age-dependent manner

PubMed Central

Zhang, Wei; Rosenkranz, J. Amiel

2013-01-01

Affective disorders are believed to involve dysfunction within the amygdala, a key structure for processing emotional information. Chronic stress may contribute to affective disorders such as depression and anxiety via its effects on the amygdala. Previous research has shown that chronic stress increases amygdala neuronal activity in an age-dependent manner. However, whether these distinct changes in amgydala neuronal activity are accompanied by age-dependent changes in amygdala-dependent affective behavior is unclear. In this study, we investigated how chronic stress impacts amgydala-dependent auditory fear conditioning in adolescent and adult rats in a repeated restraint model. We found that repeated restraint enhanced conditioned freezing in both adolescent and adult rats. But repeated restraint led to impaired acquisition of fear extinction only in adolescent rats. Along with previous findings, these results suggest that chronic stress may precipitate affective disorders via differential mechanisms, with different outcomes at different ages. PMID:23538069

Repeated assessment of orthotopic glioma pO(2) by multi-site EPR oximetry: a technique with the potential to guide therapeutic optimization by repeated measurements of oxygen.

PubMed

Khan, Nadeem; Mupparaju, Sriram; Hou, Huagang; Williams, Benjamin B; Swartz, Harold

2012-02-15

Tumor hypoxia plays a vital role in therapeutic resistance. Consequently, measurements of tumor pO(2) could be used to optimize the outcome of oxygen-dependent therapies, such as, chemoradiation. However, the potential optimizations are restricted by the lack of methods to repeatedly and quantitatively assess tumor pO(2) during therapies, particularly in gliomas. We describe the procedures for repeated measurements of orthotopic glioma pO(2) by multi-site electron paramagnetic resonance (EPR) oximetry. This oximetry approach provides simultaneous measurements of pO(2) at more than one site in the glioma and contralateral cerebral tissue. The pO(2) of intracerebral 9L, C6, F98 and U251 tumors, as well as contralateral brain, were measured repeatedly for five consecutive days. The 9L glioma was well oxygenated with pO(2) of 27-36 mm Hg, while C6, F98 and U251 glioma were hypoxic with pO(2) of 7-12mm Hg. The potential of multi-site EPR oximetry to assess temporal changes in tissue pO(2) was investigated in rats breathing 100% O(2). A significant increase in F98 tumor and contralateral brain pO(2) was observed on day 1 and day 2, however, glioma oxygenation declined on subsequent days. In conclusion, EPR oximetry provides the capability to repeatedly assess temporal changes in orthotopic glioma pO(2). This information could be used to test and optimize the methods being developed to modulate tumor hypoxia. Furthermore, EPR oximetry could be potentially used to enhance the outcome of chemoradiation by scheduling treatments at times of increase in glioma pO(2). Copyright © 2011 Elsevier B.V. All rights reserved.

MSH3 Promotes Dynamic Behavior of Trinucleotide Repeat Tracts In Vivo

PubMed Central

Williams, Gregory M.; Surtees, Jennifer A.

2015-01-01

Trinucleotide repeat (TNR) expansions are the underlying cause of more than 40 neurodegenerative and neuromuscular diseases, including myotonic dystrophy and Huntington’s disease, yet the pathway to expansion remains poorly understood. An important step in expansion is the shift from a stable TNR sequence to an unstable, expanding tract, which is thought to occur once a TNR attains a threshold length. Modeling of human data has indicated that TNR tracts are increasingly likely to expand as they increase in size and to do so in increments that are smaller than the repeat itself, but this has not been tested experimentally. Genetic work has implicated the mismatch repair factor MSH3 in promoting expansions. Using Saccharomyces cerevisiae as a model for CAG and CTG tract dynamics, we examined individual threshold-length TNR tracts in vivo over time in MSH3 and msh3Δ backgrounds. We demonstrate, for the first time, that these TNR tracts are highly dynamic. Furthermore, we establish that once such a tract has expanded by even a few repeat units, it is significantly more likely to expand again. Finally, we show that threshold- length TNR sequences readily accumulate net incremental expansions over time through a series of small expansion and contraction events. Importantly, the tracts were substantially stabilized in the msh3Δ background, with a bias toward contractions, indicating that Msh2-Msh3 plays an important role in shifting the expansion-contraction equilibrium toward expansion in the early stages of TNR tract expansion. PMID:25969461

MSH3 Promotes Dynamic Behavior of Trinucleotide Repeat Tracts In Vivo.

PubMed

Williams, Gregory M; Surtees, Jennifer A

2015-07-01

Trinucleotide repeat (TNR) expansions are the underlying cause of more than 40 neurodegenerative and neuromuscular diseases, including myotonic dystrophy and Huntington's disease, yet the pathway to expansion remains poorly understood. An important step in expansion is the shift from a stable TNR sequence to an unstable, expanding tract, which is thought to occur once a TNR attains a threshold length. Modeling of human data has indicated that TNR tracts are increasingly likely to expand as they increase in size and to do so in increments that are smaller than the repeat itself, but this has not been tested experimentally. Genetic work has implicated the mismatch repair factor MSH3 in promoting expansions. Using Saccharomyces cerevisiae as a model for CAG and CTG tract dynamics, we examined individual threshold-length TNR tracts in vivo over time in MSH3 and msh3Δ backgrounds. We demonstrate, for the first time, that these TNR tracts are highly dynamic. Furthermore, we establish that once such a tract has expanded by even a few repeat units, it is significantly more likely to expand again. Finally, we show that threshold- length TNR sequences readily accumulate net incremental expansions over time through a series of small expansion and contraction events. Importantly, the tracts were substantially stabilized in the msh3Δ background, with a bias toward contractions, indicating that Msh2-Msh3 plays an important role in shifting the expansion-contraction equilibrium toward expansion in the early stages of TNR tract expansion. Copyright © 2015 by the Genetics Society of America.

Repeated maternal intramuscular or intraamniotic erythromycin incompletely resolves intrauterine Ureaplasma parvum infection in a sheep model of pregnancy.

PubMed

Kemp, Matthew W; Miura, Yuichiro; Payne, Matthew S; Watts, Rory; Megharaj, Smruthi; Jobe, Alan H; Kallapur, Suhas G; Saito, Masatoshi; Spiller, O Brad; Keelan, Jeffrey A; Newnham, John P

2014-08-01

Ureaplasma spp are the most commonly isolated microorganisms in association with preterm birth. Maternal erythromycin administration is a standard treatment for preterm prelabor rupture of membranes. There is little evidence of its effectiveness in eradicating Ureaplasma spp from the intrauterine cavity and fetus. We used a sheep model of intrauterine Ureaplasma spp infection to investigate the efficacy of repeated maternal intramuscular and intraamniotic erythromycin treatment to eradicate such an infection. Thirty ewes with singleton pregnancies received an intraamniotic injection of 10(7) color change units of erythromycin-sensitive Ureaplasma parvum serovar 3 at 55 days' gestation. At 116 days' gestation, 28 ewes with viable fetuses were randomized to receive (1) intraamniotic and maternal intramuscular saline solution treatment (n = 8), (2) single intraamniotic and repeated maternal intramuscular erythromycin treatment (n = 10), or (3) single maternal intramuscular and repeated intraamniotic erythromycin treatment (n = 10). Fetuses were surgically delivered at 125 days' gestation. Treatment efficacy was assessed by culture, quantitative polymerase chain reaction, and histopathologic evaluation. Animals treated with intraamniotic erythromycin had significantly less viable U parvum serovar 3 in the amniotic fluid at delivery. However, neither combination of maternal intramuscular and intraamniotic erythromycin treatment successfully cleared U parvum serovar 3 from the amniotic fluid or fetal tissues. Three de novo erythromycin-resistant U parvum isolates were identified in erythromycin-treated animals. Erythromycin treatment, given both to the ewe and into the amniotic cavity, fails to eradicate intrauterine and fetal U parvum serovar 3 infection and may lead to development of erythromycin resistant U parvum. Copyright © 2014 Mosby, Inc. All rights reserved.

Dipole moments and transition probabilities of the i 3Pi sub g-b 3Sigma(+) sub u, c 3Pi sub u-a 3Sigma(+) sub g, and i 3Pi sub g-c 3Pi sub u systems of molecular hydrogen

NASA Technical Reports Server (NTRS)

Guberman, Steven L.; Dalgarno, A.

1992-01-01

Bonn-Oppenheimer-based ab initio calculations of dipole moments from the i 3Pi sub g-b 3Sigma(+) sub u, c 3Pi sub u-a 3Sigma(+) sub g, and i 3Pi sub g-c 3Pi sub u transitions of H2 have been conducted, to yield a tabulation of the dipole transition probabilities and Franck-Condon factors. These factors are given for transitions originating in the lowest vibrational level of the ground X 1Sigma(+) sub g state.

Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) for the assessment of Pc 4-sensitized photodynamic therapy of a U87-derived glioma model in the athymic nude rat

NASA Astrophysics Data System (ADS)

Anka, Ali; Thompson, Paul; Mott, Eric; Sharma, Rahul; Zhang, Ruozhen; Cross, Nathan; Sun, Jiayang; Flask, Chris A.; Oleinick, Nancy L.; Dean, David

2010-02-01

Introduction: Dynamic Contrast-Enhanced-Magnetic Resonance Imaging (DCE-MRI) may provide a means of tracking the outcome of Pc 4-sensitized photodynamic therapy (PDT) in deeply placed lesions (e.g., brain tumors). We previously determined that 150 μL of gadolinium (Gd-DTPA) produces optimal enhancement of U87-derived intracerebral tumors in an athymic nude rat glioma model. We wish to determine how consistently DCE-MRI enhancement will detect an increase in Gd-enhancement of these tumors following Pc 4-PDT. Methods: We injected 2.5 x 105 U87 cells into the brains of 6 athymic nude rats. After 7-8 days pre-Pc 4 PDT peri-tumor DCE-MRI images were acquired on a 7.0T microMRI scanner before and after administration of 150 μL Gd. DCE-MRI scans were repeated on Days 11, 12, and 13 following Pc 4-PDT (Day 8 or 9). Results: Useful DCE-MRI data were obtained for these animals before and after Pc 4- PDT. In the pre-Pc 4-PDT DCE-MRI scans an average normalized peak Gd enhancement was observed in tumor tissue that was 1.297 times greater than baseline (0.035 Standard Error [SE]). The average normalized peak Gd enhancement in the tumor tissue in the scan following PDT (Day 11) was 1.537 times greater than baseline (0.036 SE), a statistically significant increase in enhancement (p = 0.00584) over the pre-PDT level. Discussion: A 150 μL Gd dose appears to provide an unambiguous increase in signal indicating Pc 4-PDT-induced necrosis of the U87-derived tumor. Our DCEMRI protocol may allow the development of a clinically robust, unambiguous, non-invasive technique for the assessment of PDT outcome.

Strongly correlated electron behavior in single crystalline U2Os3Al9

NASA Astrophysics Data System (ADS)

Kumar, Neeraj; Das, Pranab Kumar; Kulkarni, Ruta; Thamizhavel, A.; Dhar, S. K.

2012-12-01

We report the magnetic properties of a single crystal of a new compound U2Os3Al9 which crystallizes in the well known Y2Co3Ga9 type orthorhombic structure with space group Cmcm. The susceptibility of U2Os3Al9 shows a peak at 7 K typical of antiferromagnetic ordering. The susceptibility in the paramagnetic state is anisotropic, the easy axis of magnetization lying in the ab-plane of the orthorhombic crystal lattice. The magnetization at 2 K, measured up to a maximum field of 160 kOe, shows a metamagnetic transition near 118 kOe when the field is aligned along [010] in addition to a small metamagnetic transition near 25 kOe. The bulk antiferromagnetic ordering of the uranium ions at TN = 7 K is confirmed by a peak in the heat capacity with ΔC nearly 7 J/U.mol K. An extrapolation of the heat capacity data from the paramagnetic regime to T = 0 gives an enhanced electronic specific heat coefficient of 120 mJ/U.mol K2. The electrical resistivity of U2Os3Al9 shows a negative temperature coefficient between 300 and TN which is a signature of spin fluctuations in a narrow band or a Kondo type of interaction. The data thus suggest the presence of strong electron correlations in this compound.

Fitness determinants of repeated-sprint ability in highly trained youth football players.

PubMed

Spencer, Matt; Pyne, David; Santisteban, Juanma; Mujika, Iñigo

2011-12-01

Variations in rates of growth and development in young football players can influence relationships among various fitness qualities. To investigate the relationships between repeated-sprint ability and other fundamental fitness qualities of acceleration, agility, explosive leg power, and aerobic conditioning through the age groups of U11 to U18 in highly trained junior football players. Male players (n = 119) across the age groups completed a fitness assessment battery over two testing sessions. The first session consisted of countermovement jumps without and with arm swing, 15-m sprint run, 15-m agility run, and the 20-m Shuttle Run (U11 to U15) or the Yo-Yo Intermittent Recovery Test, Level 1 (U16 to U18). The players were tested for repeated-sprint ability in the second testing session using a protocol of 6 × 30-m sprints on 30 s with an active recovery. The correlations of repeated-sprint ability with the assorted fitness tests varied considerably between the age groups, especially for agility (r = .02 to .92) and explosive leg power (r = .04 to .84). Correlations of repeated sprint ability with acceleration (r = .48 to .93) and aerobic conditioning (r = .28 to .68) were less variable with age. Repeated-sprint ability associates differently with other fundamental fitness tests throughout the teenage years in highly trained football players, although stabilization of these relationships occurs by the age of 18 y. Coaches in junior football should prescribe physical training accounting for variations in short-term disruptions or impairment of physical performance during this developmental period.

Progress of the Photovoltaic Technology Incubator Project Towards an Enhanced U.S. Manufacturing Base: Preprint

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

Ullal, H.; Mitchell, R.; Keyes, B.

In this paper, we report on the major accomplishments of the U.S. Department of Energy's (DOE) Solar Energy Technologies Program (SETP) Photovoltaic (PV) Technology Incubator project. The Incubator project facilitates a company's transition from developing a solar cell or PV module prototype to pilot- and large-scale U.S. manufacturing. The project targets small businesses that have demonstrated proof-of-concept devices or processes in the laboratory. Their success supports U.S. Secretary of Energy Steven Chu's SunShot Initiative, which seeks to achieve PV technologies that are cost-competitive without subsidies at large scale with fossil-based energy sources by the end of this decade. The Incubatormore » Project has enhanced U.S. PV manufacturing capacity and created more than 1200 clean energy jobs, resulting in an increase in American economic competitiveness. The investment raised to date by these PV Incubator companies as a result of DOE's $ 59 million investment totals nearly $ 1.3 billion.« less

Strategies to Improve Repeat Fecal Occult Blood Testing Cancer Screening

PubMed Central

Davis, Terry C.; Arnold, Connie L.; Bennett, Charles L.; Wolf, Michael S.; Reynolds, Cristalyn; Liu, Dachao; Rademaker, Alfred

2013-01-01

Background A comparative effectiveness intervention by this team improved initial fecal occult blood testing (FOBT) rates from 3% to 53% among community clinic patients. The purpose of this study was to evaluate the effectiveness and costs associated with a literacy-informed intervention on repeat FOBT testing. Methods Between 2008 and 2011, a three-arm quasi-experiential comparative effectiveness evaluation was conducted in 8 community clinics in Louisiana. Clinics were randomly assigned to receive: enhanced care, a screening recommendation and FOBT kit annually; a brief educational intervention where patients additionally received a literacy appropriate pamphlet and simplified FOBT instructions; or nurse support where a nurse manager provided the education and followed up with phone support. In year 2 all materials were mailed. The study consisted of 461 patients, ages 50–85, with a negative initial FOBT. Results Repeat FOBT rates were 38% enhanced care, 33% education, and 59% with nurse support (p=0.017). After adjusting for age, race, gender, and literacy, patients receiving nurse support were 1.46 times more likely to complete repeat FOBT screening than those receiving education (95% CI 1.14–1.06, p=0.002) and 1.45 times more likely than those in enhanced care but this was not significant (95% CI 0.93–2.26 p=0.10). The incremental cost per additional person screened was $2,450 for nurse over enhanced care. Conclusion A mailed pamphlet and FOBT with simplified instructions did not improve annual screening. Impact Telephone outreach by a nurse manager was effective in improving rates of repeat FOBT yet this may be too costly for community clinics. PMID:24192009

Non-stoichiometry in U 3Si 2

DOE PAGES

Middleburgh, Simon C.; Grimes, Robin W.; Lahoda, Ed J.; ...

2016-10-08

Uranium silicides, in particular U 3Si 2, are being explored as an advanced nuclear fuel with increased accident tolerance as well as competitive economics compared to the baseline UO 2 fuel. Here we use density functional theory calculations and thermochemical analysis to assess the stability of U 3Si 2 with respect to non-stoichiometry reactions in both the hypo- and hyper-stoichiometric regimes. We find that the degree of non-stoichiometry in U 3Si 2 is much smaller than in UO 2 and at most reaches a few percent at high temperature. Non-stoichiometry impacts fuel performance by determining whether the loss of uraniummore » due to fission leads to a non-stoichiometric U 3Si 2±x phase or precipitation of a second U-Si phase. Lastly, we also investigate the U 5Si 4 phase as a candidate for the equilibrium phase diagram.« less

The VBP and a1/EBP leucine zipper factors bind overlapping subsets of avian retroviral long terminal repeat CCAAT/enhancer elements.

PubMed

Smith, C D; Baglia, L A; Curristin, S M; Ruddell, A

1994-10-01

Two long terminal repeat (LTR) enhancer-binding proteins which may regulate high rates of avian leukosis virus (ALV) LTR-enhanced c-myc transcription during bursal lymphomagenesis have been identified (A. Ruddell, M. Linial, and M. Groudine, Mol. Cell. Biol. 9:5660-5668, 1989). The genes encoding the a1/EBP and a3/EBP binding factors were cloned by expression screening of a lambda gt11 cDNA library from chicken bursal lymphoma cells. The a1/EBP cDNA encodes a novel leucine zipper transcription factor (W. Bowers and A. Ruddell, J. Virol. 66:6578-6586, 1992). The partial a3/EBP cDNA clone encodes amino acids 84 to 313 of vitellogenin gene-binding protein (VBP), a leucine zipper factor that binds the avian vitellogenin II gene promoter (S. Iyer, D. Davis, and J. Burch, Mol. Cell. Biol. 11:4863-4875, 1991). Multiple VBP mRNAs are expressed in B cells in a pattern identical to that previously observed for VBP in other cell types. The LTR-binding activities of VBP, a1/EBP, and B-cell nuclear extract protein were compared and mapped by gel shift, DNase I footprinting, and methylation interference assays. The purified VBP and a1/EBP bacterial fusion proteins bind overlapping but distinct subsets of CCAAT/enhancer elements in the closely related ALV and Rous sarcoma virus (RSV) LTR enhancers. Protein binding to these CCAAT/enhancer elements accounts for most of the labile LTR enhancer-binding activity observed in B-cell nuclear extracts. VBP and a1/EBP could mediate the high rates of ALV and RSV LTR-enhanced transcription in bursal lymphoma cells and many other cell types.

Enhanced Performance of Perovskite CH3NH3PbI3 Solar Cell by Using CH3NH3I as Additive in Sequential Deposition.

PubMed

Xie, Yian; Shao, Feng; Wang, Yaoming; Xu, Tao; Wang, Deliang; Huang, Fuqiang

2015-06-17

Sequential deposition is a widely adopted method to prepare CH3NH3PbI3 on mesostructured TiO2 electrode for organic lead halide perovskite solar cells. However, this method often suffers from the uncontrollable crystal size, surface morphology, and residual PbI2 in the resulting CH3NH3PbI3, which are all detrimental to the device performance. We herein present an optimized sequential solution deposition method by introducing different amount of CH3NH3I in PbI2 precursor solution in the first step to prepare CH3NH3PbI3 absorber on mesoporous TiO2 substrates. The addition of CH3NH3I in PbI2 precursor solution can affect the crystallization and composition of PbI2 raw films, resulting in the variation of UV-vis absorption and surface morphology. Proper addition of CH3NH3I not only enhances the absorption but also improves the efficiency of CH3NH3PbI3 solar cells from 11.13% to 13.37%. Photoluminescence spectra suggest that the improvement of device performance is attributed to the decrease of recombination rate of carriers in CH3NH3PbI3 absorber. This current method provides a highly repeatable route for enhancing the efficiency of CH3NH3PbI3 solar cell in the sequential solution deposition method.

Security enhancement study for the U.S. motorcoach industry : executive summary

DOT National Transportation Integrated Search

2003-05-01

The Security Enhancement Study for the U.S. Motorcoach Industry was commissioned by the Federal Motor Carrier Safety Administration (FMCSA) and conducted by the John A. Volpe National Transportation Systems Center (Volpe Center). It was prepared to i...

The repeat organizer, a specialized insulator element within the intergenic spacer of the Xenopus rRNA genes.

PubMed Central

Robinett, C C; O'Connor, A; Dunaway, M

1997-01-01

We have identified a novel activity for the region of the intergenic spacer of the Xenopus laevis rRNA genes that contains the 35- and 100-bp repeats. We devised a new assay for this region by constructing DNA plasmids containing a tandem repeat of rRNA reporter genes that were separated by the 35- and 100-bp repeat region and a rRNA gene enhancer. When the 35- and 100-bp repeat region is present in its normal position and orientation at the 3' end of the rRNA reporter genes, the enhancer activates the adjacent downstream promoter but not the upstream rRNA promoter on the same plasmid. Because this element can restrict the range of an enhancer's activity in the context of tandem genes, we have named it the repeat organizer (RO). The ability to restrict enhancer action is a feature of insulator elements, but unlike previously described insulator elements the RO does not block enhancer action in a simple enhancer-blocking assay. Instead, the activity of the RO requires that it be in its normal position and orientation with respect to the other sequence elements of the rRNA genes. The enhancer-binding transcription factor xUBF also binds to the repetitive sequences of the RO in vitro, but these sequences do not activate transcription in vivo. We propose that the RO is a specialized insulator element that organizes the tandem array of rRNA genes into single-gene expression units by promoting activation of a promoter by its proximal enhancers. PMID:9111359

Density functional theory calculations of UO2 oxidation: evolution of UO(2+x), U4O(9-y), U3O7, and U3O8.

PubMed

Andersson, D A; Baldinozzi, G; Desgranges, L; Conradson, D R; Conradson, S D

2013-03-04

Formation of hyperstoichiometric uranium dioxide, UO2+x, derived from the fluorite structure was investigated by means of density functional theory (DFT) calculations. Oxidation was modeled by adding oxygen atoms to UO2 fluorite supercells. For each compound ab initio molecular dynamics simulations were performed to allow the ions to optimize their local geometry. A similar approach was used for studying the reduction of U3O8. In agreement with the experimental phase diagram we identify stable line compounds at the U4O9-y and U3O7 stoichiometries. Although the transition from fluorite to the layered U3O8 structure occurs at U3O7 (UO2.333) or U3O7.333 (UO2.444), our calculated low temperature phase diagram indicates that the fluorite derived compounds are favored up to UO2.5, that is, as long as the charge-compensation for adding oxygen atoms occurs via formation of U(5+) ions, after which the U3O8-y phase becomes more stable. The most stable fluorite UO2+x phases at low temperature (0 K) are based on ordering of split quad-interstitial oxygen clusters. Most existing crystallographic models of U4O9 and U3O7, however, apply the cuboctahedral cluster. To better understand these discrepancies, the new structural models are analyzed in terms of existing neutron diffraction data. DFT calculations were also performed on the experimental cuboctahedral based U4O9-y structure, which enable comparisons between the properties of this phase with the quad-interstitial ones in detail.

Magnoflorine Enhances LPS-Activated Pro-Inflammatory Responses via MyD88-Dependent Pathways in U937 Macrophages.

PubMed

Haque, Md Areeful; Jantan, Ibrahim; Harikrishnan, Hemavathy; Abdul Wahab, Siti Mariam

2018-06-15

Magnoflorine, a major bioactive metabolite isolated from Tinospora crispa, has been reported for its diverse biochemical and pharmacological properties. However, there is little report on its underlying mechanisms of action on immune responses, particularly on macrophage activation. In this study, we aimed to investigate the effects of magnoflorine, isolated from T. crispa on the pro-inflammatory mediators generation induced by LPS and the concomitant NF- κ B, MAPKs, and PI3K-Akt signaling pathways in U937 macrophages. Differentiated U937 macrophages were treated with magnoflorine and the release of pro-inflammatory mediators was evaluated through ELISA, while the relative mRNA expression of the respective mediators was quantified through qRT-PCR. Correspondingly, western blotting was executed to observe the modulatory effects of magnoflorine on the expression of various markers related to NF- κ B, MAPK and PI3K-Akt signaling activation in LPS-primed U937 macrophages. Magnoflorine significantly enhanced the upregulation of TNF- α , IL-1 β , and PGE 2 production as well as COX-2 protein expression. Successively, magnoflorine prompted the mRNA transcription level of these pro-inflammatory mediators. Magnoflorine enhanced the NF- κ B activation by prompting p65, I κ B α , and IKK α / β phosphorylation as well as I κ B α degradation. Besides, magnoflorine treatments concentration-dependently augmented the phosphorylation of JNK, ERK, and p38 MAPKs as well as Akt. The immunoaugmenting effects were further confirmed by investigating the effects of magnoflorine on specific inhibitors, where the treatment with specific inhibitors of NF- κ B, MAPKs, and PI3K-Akt proficiently blocked the magnoflorine-triggered TNF- α release and COX-2 expression. Magnoflorine furthermore enhanced the MyD88 and TLR4 upregulation. The results suggest that magnoflorine has high potential on augmenting immune responses. Georg Thieme Verlag KG Stuttgart · New York.

The role of unstable NH3 in the formation of nitrogen-rich alpha-U2N(3+x) by the reaction of UC or U with NH3

NASA Astrophysics Data System (ADS)

Katsura, Masahiro; Hirota, Masayuki; Miyake, Masanobu

1994-10-01

Reactions of U or UC with a stream of NH3 or N2 were carried out at 600 and 900 C. It has been found that in high temperature reactions of U or UC with flowing NH3, the catalytic decomposition of NH3 proceeds in parallel with the nitridation reaction of U or UC by action of NH3, which leads to the formation alpha-U2N(3+x), and eventually a steady state is established where the partial pressures of NH3, H2 and N2 (PNH3, PH2, and PN2) in the flowing gas and the N:U ratio of alpha-U2N(3+x) are all uniquely determined. The nitrogen activity a(sub N) of the flowing gas may be increased by suppressing the decomposition of NH3 into H2 and N2. The N:U ratio of alpha-U2N(3+x) increases as the extent of dissociation of NH3, alpha, decreases.

U-2012: An improved Lowry protein assay, insensitive to sample color, offering reagent stability and enhanced sensitivity.

PubMed

Upreti, Girish C; Wang, Yanming; Finn, Alona; Sharrock, Abigail; Feisst, Nicholas; Davy, Marcus; Jordan, Robert B

2012-03-01

Traditional colorimetric protein assays such as Biuret, Lowry, and modified Lowry (U-1988) are unsuitable for colored biological samples. Here we describe an improved Lowry protein assay (U-2012), which utilizes stable reagents and offers enhanced sensitivity over the U-1988 assay. U-2012 circumvents interference from colored pigments and other substances (for example sugars) bound to perchloric acid (PCA) precipitated proteins by hydrogen peroxide (H2O2) induced oxidation at 50°C. Unused hydrogen peroxide is neutralized with sodium pyruvate before protein estimation for a stable end color. The U-2012 assay is carried out on the PCA precipitated protein pellet after neutralization (with Na2CO3 plus NaOH), solubilization (in Triton-NaCl), decolorization (by H2O2) and pyruvate treatment. Protein contents in red wine and homogenates of beetroot and blueberry are calculated from standard curves established for various proteins and generated using a rectangular hyperbola with parameters estimated with Microsoft Excel's Solver add-in. The U-2012 protein assay represents an improvement over U-1988 and gives a more accurate estimation of protein content.

Neurogenesis enhancer RO 25-6981 facilitates repeated spatial learning in adult rats.

PubMed

Soloviova, O A; Proshin, A T; Storozheva, Z I; Sherstnev, V V

2012-09-01

The effects of Ro 25-6981 (selective NMDA receptor blocker) in a dose stimulating neurogenesis on repeated learning, reversal learning, and memory reconsolidation were studied in adult rats in Morris water maze. Ro 25-6981 facilitated repeated learning 13 days after injection, but did not influence reversal learning. The blocker injected directly before reminder did not disturb repeated learning and reversal learning in Morris water maze. These effects of Ro 25-6981 on the dynamics of repeated learning seemed to be due to its effects on neurogenesis processes in adult brain.

Repeatability of quantitative FDG-PET/CT and contrast-enhanced CT in recurrent ovarian carcinoma: test-retest measurements for tumor FDG uptake, diameter, and volume.

PubMed

Rockall, Andrea G; Avril, Norbert; Lam, Raymond; Iannone, Robert; Mozley, P David; Parkinson, Christine; Bergstrom, Donald; Sala, Evis; Sarker, Shah-Jalal; McNeish, Iain A; Brenton, James D

2014-05-15

Repeatability of baseline FDG-PET/CT measurements has not been tested in ovarian cancer. This dual-center, prospective study assessed variation in tumor 2[18F]fluoro-2-deoxy-D-glucose (FDG) uptake, tumor diameter, and tumor volume from sequential FDG-PET/CT and contrast-enhanced computed tomography (CECT) in patients with recurrent platinum-sensitive ovarian cancer. Patients underwent two pretreatment baseline FDG-PET/CT (n = 21) and CECT (n = 20) at two clinical sites with different PET/CT instruments. Patients were included if they had at least one target lesion in the abdomen with a standardized uptake value (SUV) maximum (SUVmax) of ≥ 2.5 and a long axis diameter of ≥ 15 mm. Two independent reading methods were used to evaluate repeatability of tumor diameter and SUV uptake: on site and at an imaging clinical research organization (CRO). Tumor volume reads were only performed by CRO. In each reading set, target lesions were independently measured on sequential imaging. Median time between FDG-PET/CT was two days (range 1-7). For site reads, concordance correlation coefficients (CCC) for SUVmean, SUVmax, and tumor diameter were 0.95, 0.94, and 0.99, respectively. Repeatability coefficients were 16.3%, 17.3%, and 8.8% for SUVmean, SUVmax, and tumor diameter, respectively. Similar results were observed for CRO reads. Tumor volume CCC was 0.99 with a repeatability coefficient of 28.1%. There was excellent test-retest repeatability for FDG-PET/CT quantitative measurements across two sites and two independent reading methods. Cutoff values for determining change in SUVmean, SUVmax, and tumor volume establish limits to determine metabolic and/or volumetric response to treatment in platinum-sensitive relapsed ovarian cancer. ©2014 American Association for Cancer Research.

Large-Pore 3D Cubic Mesoporous (KIT-6) Hybrid Bearing a Hard-Soft Donor Combined Ligand for Enhancing U(VI) Capture: An Experimental and Theoretical Investigation.

PubMed

Yuan, Li-Yong; Zhu, Lin; Xiao, Cheng-Liang; Wu, Qun-Yan; Zhang, Nan; Yu, Ji-Pan; Chai, Zhi-Fang; Shi, Wei-Qun

2017-02-01

A preorganized tetradentate phenanthrolineamide (DAPhen) ligand with hard and soft donors combined in the same molecule has been found to possess high extraction ability toward actinides over lanthanides from acidic aqueous solution in our previous work. Herein we grafted phenanthrolineamide groups onto a large-pore three-dimensional cubic silica support by the reaction of DAPhen siloxane with KIT-6 substrate to prepare a novel uranium-selective sorbent, KIT-6-DAPhen. The as-synthesized sorbent was well-characterized by scanning electron microscopy, high-resolution transmission electron microscopy, N 2 adsorption/desorption, X-ray diffraction, FT-IR, 13 C cross-polarization magic-angle spinning NMR, and TGA techniques, which confirmed the consummation of the functionalization. Subsequently, the effects of contact time, solution pH, initial U(VI) concentration, and the presence of competing metal ions on the U(VI) sorption onto KIT-6-DAPhen sorbent were investigated in detail. It was found that KIT-6-DAPhen showed largely enhanced sorption capacity and excellent selectivity toward U(VI). The maximum sorption capacity of KIT-6-DAPhen at pH 5.0 reaches 328 mg of U/g of sorbent, which is superior to most of functionalized mesoporous silica materials. Density functional theory coupled with quasi-relativistic small-core pseudopotentials was used to explore the sorption interaction between U(VI) and KIT-6-DAPhen, which gives a sorption reaction of KIT-6-DAPhen + [UO 2 (H 2 O) 5 ] 2+ + NO 3 - ⇄ [UO 2 (KIT-6-DAPhen)(NO 3 )] + + 5H 2 O. The findings of the present work provide new clues for developing new actinide sorbents by combining new ligands with various mesoporous matrixes.

Pulmonary ventilation imaging in asthma and cystic fibrosis using oxygen-enhanced 3D radial ultrashort echo time MRI.

PubMed

Zha, Wei; Kruger, Stanley J; Johnson, Kevin M; Cadman, Robert V; Bell, Laura C; Liu, Fang; Hahn, Andrew D; Evans, Michael D; Nagle, Scott K; Fain, Sean B

2018-05-01

A previous study demonstrated the feasibility of using 3D radial ultrashort echo time (UTE) oxygen-enhanced MRI (UTE OE-MRI) for functional imaging of healthy human lungs. The repeatability of quantitative measures from UTE OE-MRI needs to be established prior to its application in clinical research. To evaluate repeatability of obstructive patterns in asthma and cystic fibrosis (CF) with UTE OE-MRI with isotropic spatial resolution and full chest coverage. Volunteer and patient repeatability. Eighteen human subjects (five asthma, six CF, and seven normal subjects). Respiratory-gated free-breathing 3D radial UTE (80 μs) sequence at 1.5T. Two 3D radial UTE volumes were acquired sequentially under normoxic and hyperoxic conditions. A subset of subjects underwent repeat acquisitions on either the same day or ≤15 days apart. Asthma and CF subjects also underwent spirometry. A workflow including deformable registration and retrospective lung density correction was used to compute 3D isotropic percent signal enhancement (PSE) maps. Median PSE (MPSE) and ventilation defect percent (VDP) of the lung were measured from the PSE map. The relations between MPSE, VDP, and spirometric measures were assessed using Spearman correlations. The test-retest repeatability was evaluated using Bland-Altman analysis and intraclass correlation coefficients (ICC). Ventilation measures in normal subjects (MPSE = 8.0%, VDP = 3.3%) were significantly different from those in asthma (MPSE = 6.0%, P = 0.042; VDP = 21.7%, P = 0.018) and CF group (MPSE = 4.5%, P = 0.0006; VDP = 27.2%, P = 0.002). MPSE correlated significantly with forced expiratory lung volume in 1 second percent predicted (ρ = 0.72, P = 0.017). The ICC of the test-retest VDP and MPSE were both ≥0.90. In all subject groups, an anterior/posterior gradient was observed with higher MPSE and lower VDP in the posterior compared to anterior regions (P ≤ 0.0021 for all comparisons

Knudsen effusion mass spectrometric studies over (USn3+U3Sn7) two-phase region of U-Sn system

NASA Astrophysics Data System (ADS)

Manikandan, P.; Trinadh, V. V.; Bera, Suranjan; Narasimhan, T. S. Lakshmi; Ananthasivan, K.; Joseph, M.; Mudali, U. Kamachi

2017-08-01

Vaporisation studies over (USn3+U3Sn7) ;two-phase; field have been carried out by employing Knudsen effusion mass spectrometry (KEMS) in the temperature range of 1050-1226 K. Sn(g) was the species observed in the mass spectrum of the equilibrium vapour phase over the samples (71.5 at% Sn and 73.0 at% Sn). The partial pressure of Sn(g) was measured as a function of temperature over (USn3+U3Sn7) ;two-phase; field and the p-T relation was derived as log (pSn/Pa) = ((-14580 ± 91)/(T/K)) + (8.82 ± 0.08) (1050-1226 K). The vaporisation reaction 3USn3(s) = U3Sn7(s) + 2Sn(g) was evaluated by second law method. The Gibbs energy of formation of USn3(s) was derived as ΔfGm°(U Sn3 , s , T) (±1.8) = -173.4 + 0.055 T (K) (kJ mol-1) (1050-1226 K). The mass spectrometric studies on this system have been carried out for the first time.

Central gene expression changes associated with enhanced neuroendocrine and autonomic response habituation to repeated noise stress after voluntary wheel running in rats

PubMed Central

Sasse, Sarah K.; Nyhuis, Tara J.; Masini, Cher V.; Day, Heidi E. W.; Campeau, Serge

2013-01-01

Accumulating evidence indicates that regular physical exercise benefits health in part by counteracting some of the negative physiological impacts of stress. While some studies identified reductions in some measures of acute stress responses with prior exercise, limited data were available concerning effects on cardiovascular function, and reported effects on hypothalamic-pituitary-adrenocortical (HPA) axis responses were largely inconsistent. Given that exposure to repeated or prolonged stress is strongly implicated in the precipitation and exacerbation of illness, we proposed the novel hypothesis that physical exercise might facilitate adaptation to repeated stress, and subsequently demonstrated significant enhancement of both HPA axis (glucocorticoid) and cardiovascular (tachycardia) response habituation to repeated noise stress in rats with long-term access to running wheels compared to sedentary controls. Stress habituation has been attributed to modifications of brain circuits, but the specific sites of adaptation and the molecular changes driving its expression remain unclear. Here, in situ hybridization histochemistry was used to examine regulation of select stress-associated signaling systems in brain regions representing likely candidates to underlie exercise-enhanced stress habituation. Analyzed brains were collected from active (6 weeks of wheel running) and sedentary rats following control, acute, or repeated noise exposures that induced a significantly faster rate of glucocorticoid response habituation in active animals but preserved acute noise responsiveness. Nearly identical experimental manipulations also induce a faster rate of cardiovascular response habituation in exercised, repeatedly stressed rats. The observed regulation of the corticotropin-releasing factor and brain-derived neurotrophic factor systems across several brain regions suggests widespread effects of voluntary exercise on central functions and related adaptations to stress across

PolyQ repeat expansions in ATXN2 associated with ALS are CAA interrupted repeats.

PubMed

Yu, Zhenming; Zhu, Yongqing; Chen-Plotkin, Alice S; Clay-Falcone, Dana; McCluskey, Leo; Elman, Lauren; Kalb, Robert G; Trojanowski, John Q; Lee, Virginia M-Y; Van Deerlin, Vivianna M; Gitler, Aaron D; Bonini, Nancy M

2011-03-29

Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressive disease leading to paralysis and death. Recently, intermediate length polyglutamine (polyQ) repeats of 27-33 in ATAXIN-2 (ATXN2), encoding the ATXN2 protein, were found to increase risk for ALS. In ATXN2, polyQ expansions of ≥ 34, which are pure CAG repeat expansions, cause spinocerebellar ataxia type 2. However, similar length expansions that are interrupted with other codons, can present atypically with parkinsonism, suggesting that configuration of the repeat sequence plays an important role in disease manifestation in ATXN2 polyQ expansion diseases. Here we determined whether the expansions in ATXN2 associated with ALS were pure or interrupted CAG repeats, and defined single nucleotide polymorphisms (SNPs) rs695871 and rs695872 in exon 1 of the gene, to assess haplotype association. We found that the expanded repeat alleles of 40 ALS patients and 9 long-repeat length controls were all interrupted, bearing 1-3 CAA codons within the CAG repeat. 21/21 expanded ALS chromosomes with 3CAA interruptions arose from one haplotype (GT), while 18/19 expanded ALS chromosomes with <3CAA interruptions arose from a different haplotype (CC). Moreover, age of disease onset was significantly earlier in patients bearing 3 interruptions vs fewer, and was distinct between haplotypes. These results indicate that CAG repeat expansions in ATXN2 associated with ALS are uniformly interrupted repeats and that the nature of the repeat sequence and haplotype, as well as length of polyQ repeat, may play a role in the neurological effect conferred by expansions in ATXN2.

Medial temporal lobe-dependent repetition suppression and enhancement due to implicit vs. explicit processing of individual repeated search displays

PubMed Central

Geyer, Thomas; Baumgartner, Florian; Müller, Hermann J.; Pollmann, Stefan

2012-01-01

Using visual search, functional magnetic resonance imaging (fMRI) and patient studies have demonstrated that medial temporal lobe (MTL) structures differentiate repeated from novel displays—even when observers are unaware of display repetitions. This suggests a role for MTL in both explicit and, importantly, implicit learning of repeated sensory information (Greene et al., 2007). However, recent behavioral studies suggest, by examining visual search and recognition performance concurrently, that observers have explicit knowledge of at least some of the repeated displays (Geyer et al., 2010). The aim of the present fMRI study was thus to contribute new evidence regarding the contribution of MTL structures to explicit vs. implicit learning in visual search. It was found that MTL activation was increased for explicit and, respectively, decreased for implicit relative to baseline displays. These activation differences were most pronounced in left anterior parahippocampal cortex (aPHC), especially when observers were highly trained on the repeated displays. The data are taken to suggest that explicit and implicit memory processes are linked within MTL structures, but expressed via functionally separable mechanisms (repetition-enhancement vs. -suppression). They further show that repetition effects in visual search would have to be investigated at the display level. PMID:23060776

Repeated homotypic stress elevates 2-arachidonoylglycerol levels and enhances short-term endocannabinoid signaling at inhibitory synapses in basolateral amygdala.

PubMed

Patel, Sachin; Kingsley, Philip J; Mackie, Ken; Marnett, Lawrence J; Winder, Danny G

2009-12-01

Psychosocial stress is a risk factor for development and exacerbation of neuropsychiatric illness. Repeated stress causes biochemical adaptations in endocannabinoid (eCB) signaling that contribute to stress-response habituation, however, the synaptic correlates of these adaptations have not been examined. Here, we show that the synthetic enzyme for the eCB 2-arachidonoylglycerol (2-AG), diacylglycerol (DAG) lipase alpha, is heterogeneously expressed in the amygdala, and that levels of 2-AG and precursor DAGs are increased in the basolateral amygdala (BLA) after 10 days, but not 1 day, of restraint stress. In contrast, arachidonic acid was decreased after both 1 and 10 days of restraint stress. To examine the synaptic correlates of these alterations in 2-AG metabolism, we used whole-cell electrophysiology to determine the effects of restraint stress on depolarization-induced suppression of inhibition (DSI) in the BLA. A single restraint stress exposure did not alter DSI compared with control mice. However, after 10 days of restraint stress, DSI duration, but not magnitude, was significantly prolonged. Inhibition of 2-AG degradation with MAFP also prolonged DSI duration; the effects of repeated restraint stress and MAFP were mutually occlusive. These data indicate that exposure to repeated, but not acute, stress produces neuroadaptations that confer BLA neurons with an enhanced capacity to elevate 2-AG content and engage in 2-AG-mediated short-term retrograde synaptic signaling. We suggest stress-induced enhancement of eCB-mediated suppression of inhibitory transmission in the BLA could contribute to affective dysregulation associated with chronic stress.

The environmental and economic impact of removing growth-enhancing technologies from U.S. beef production.

PubMed

Capper, J L; Hayes, D J

2012-10-01

The objective of this study was to quantify the environmental and economic impact of withdrawing growth-enhancing technologies (GET) from the U.S. beef production system. A deterministic model based on the metabolism and nutrient requirements of the beef population was used to quantify resource inputs and waste outputs per 454 × 10(6) kg of beef. Two production systems were compared: one using GET (steroid implants, in-feed ionophores, in-feed hormones, and beta-adrenergic agonists) where approved by FDA at current adoption rates and the other without GET use. Both systems were modeled using characteristic management practices, population dynamics, and production data from U.S. beef systems. The economic impact and global trade and carbon implications of GET withdrawal were calculated based on feed savings. Withdrawing GET from U.S. beef production reduced productivity (growth rate and slaughter weight) and increased the population size required to produce 454 × 10(6) kg beef by 385 × 10(3) animals. Feedstuff and land use were increased by 2,830 × 10(3) t and 265 × 10(3) ha, respectively, by GET withdrawal, with 20,139 × 10(6) more liters of water being required to maintain beef production. Manure output increased by 1,799 × 10(3) t as a result of GET withdrawal, with an increase in carbon emissions of 714,515 t/454 × 10(6) kg beef. The projected increased costs of U.S. beef produced without GET resulted in the effective implementation of an 8.2% tax on beef production, leading to reduced global trade and competitiveness. To compensate for the increase in U.S. beef prices and maintain beef supply, it would be necessary to increase beef production in other global regions, with a projected increase in carbon emissions from deforestation, particularly in Brazil. Withdrawing GET from U.S. beef production would reduce both the economic and environmental sustainability of the industry.

Repeatability of Non–Contrast-Enhanced Lower-Extremity Angiography Using the Flow-Spoiled Fresh Blood Imaging

PubMed Central

Zhang, Yuyang; Xing, Zhen; She, Dejun; Huang, Nan; Cao, Dairong

2018-01-01

Purpose The aim of this study was to prospectively evaluate the repeatability of non–contrast-enhanced lower-extremity magnetic resonance angiography using the flow-spoiled fresh blood imaging (FS-FBI). Methods Forty-three healthy volunteers and 15 patients with lower-extremity arterial stenosis were recruited in this study and were examined by FS-FBI. Digital subtraction angiography was performed within a week after the FS-FBI in the patient group. Repeatability was assessed by the following parameters: grading of image quality, diameter and area of major arteries, and grading of stenosis of lower-extremity arteries. Two experienced radiologists blinded for patient data independently evaluated the FS-FBI and digital subtraction angiography images. Intraclass correlation coefficients (ICCs), sensitivity, and specificity were used for statistical analysis. Results The grading of image quality of most data was satisfactory. The ICCs for the first and second measures were 0.792 and 0.884 in the femoral segment and 0.803 and 0.796 in the tibiofibular segment for healthy volunteer group, 0.873 and 1.000 in the femoral segment, and 0.737 and 0.737 in the tibiofibular segment for the patient group. Intraobserver and interobserver agreements on diameter and area of arteries were excellent, with ICCs mostly greater than 0.75 in the volunteer group. For stenosis grading analysis, intraobserver ICCs range from 0.784 to 0.862 and from 0.778 to 0.854, respectively. Flow-spoiled fresh blood imaging yielded a mean sensitivity and specificity to detect arterial stenosis or occlusion of 90% and 80% for femoral segment and 86.7% and 93.3% for tibiofibular segment at least. Conclusions Lower-extremity angiography with FS-FBI is a reliable and reproducible screening tool for lower-extremity atherosclerotic disease, especially for patients with impaired renal function. PMID:28787351

Repeatability of Non-Contrast-Enhanced Lower-Extremity Angiography Using the Flow-Spoiled Fresh Blood Imaging.

PubMed

Zhang, Yuyang; Xing, Zhen; She, Dejun; Huang, Nan; Cao, Dairong

The aim of this study was to prospectively evaluate the repeatability of non-contrast-enhanced lower-extremity magnetic resonance angiography using the flow-spoiled fresh blood imaging (FS-FBI). Forty-three healthy volunteers and 15 patients with lower-extremity arterial stenosis were recruited in this study and were examined by FS-FBI. Digital subtraction angiography was performed within a week after the FS-FBI in the patient group. Repeatability was assessed by the following parameters: grading of image quality, diameter and area of major arteries, and grading of stenosis of lower-extremity arteries. Two experienced radiologists blinded for patient data independently evaluated the FS-FBI and digital subtraction angiography images. Intraclass correlation coefficients (ICCs), sensitivity, and specificity were used for statistical analysis. The grading of image quality of most data was satisfactory. The ICCs for the first and second measures were 0.792 and 0.884 in the femoral segment and 0.803 and 0.796 in the tibiofibular segment for healthy volunteer group, 0.873 and 1.000 in the femoral segment, and 0.737 and 0.737 in the tibiofibular segment for the patient group. Intraobserver and interobserver agreements on diameter and area of arteries were excellent, with ICCs mostly greater than 0.75 in the volunteer group. For stenosis grading analysis, intraobserver ICCs range from 0.784 to 0.862 and from 0.778 to 0.854, respectively. Flow-spoiled fresh blood imaging yielded a mean sensitivity and specificity to detect arterial stenosis or occlusion of 90% and 80% for femoral segment and 86.7% and 93.3% for tibiofibular segment at least. Lower-extremity angiography with FS-FBI is a reliable and reproducible screening tool for lower-extremity atherosclerotic disease, especially for patients with impaired renal function.

Differential Cross Sections for the Electron Impact Excitation of the A(sup 3)(Sigma)(sub u)(sup +), B(sup 3)Pi(sub g), W(sup 3)(Delta)(sub u), B'(sup 3)(Sigma)(sub u)(sup -), a'(sup 1)Sigma(sub u)(sup -), a(sup 1)Pi(sub g), w(sup 1)Delta(sub u), and C(sup 3)Pi(sub u) States of N(sub 2)

NASA Technical Reports Server (NTRS)

Khakoo, M. A.; Johnson, P. V.; Ozkay, I.; Yan, P.; Trajmar, S.; Kanik, I.

2005-01-01

Measurements of differential cross sections for the electron-impact excitation of molecular nitrogen from the ground X(sup 1)(Sigma)(sub g)(sup +)(v''=0)level to the A(sup 3)(Sigma)(sub u)(sup +)(v'), B(sup 3)Pi(sub g)(v'), W(sup 3)(Delta)(sub u)(v'),B'(sup 3)(Sigma)(sub u)(sup -)(v'), a(sup 1)(Pi)(sub g)(v'), w(sup 1)(Delta)(sub u)(v'), and C(sup 3)(Pi)(sub u)(v') levels are presented. The data are obtained at the incident energies of 10, 12.5, 15, 17.5, 20, 30, 50, and 100 eV over the angular range of 5(deg)-130(deg) in 5(deg) intervals. The individual electronic state excitation differential cross sections are obtained by unfolding electron energy-loss spectra of molecular nitrogen using available semiempirical Frank-Condon factors. The data are compared to previous measurements and to available theory. We also make several important suggestions regarding future work that, like the present, relies on the unfolding of electron energy-loss spectra for obtaining differential cross sections.

Humic Acids Enhanced U(VI) Attenuation in Acidic Waste Plumes: An In-situ Remediation Approach

NASA Astrophysics Data System (ADS)

Wan, J.; Dong, W.; Tokunaga, T. K.

2010-12-01

In the process of extracting plutonium for nuclear weapons production during the Cold War, large volumes of acidic waste solutions containing low-level radionuclides were discharged for decades into unlined seepage basins in several US Department of Energy (DOE) weapon facilities such as the Savannah River Site (SRS), Oak Ridge (OR), and 300 Area of the Hanford Site. Although the basins have been capped and some sites have gone through many years of active remediation, groundwaters currently remain acidic with pH values as low as 3.0 near the basins, and uranium concentrations remain much higher than its maximum contaminant level (MCL). A sustainable U biogeochemical remediation method has not yet been developed, especially under acidic conditions (pH 3-5). Bioreduction-based U remediation requires permanent maintenance of reducing conditions through indefinite supply of electron donor, and when applied in acidic plumes a high-cost pretreatment procedure is required. Methods based on precipitation of phosphate minerals depend on maintenance of high P concentrations. Precipitating of uranyl vanadates can lower U to below its MCL, but this approach is only effective at near-neutral pH. There is an urgent need for developing a sustainable method to control U mobility in acidic conditions. In this paper, we propose a method of using humic acids (HAs) to attenuate contaminant U mobility in acidic waste plumes. Our laboratory experiment results show that HAs are able to strongly and quickly adsorb onto aquifer sediments from the DOE’s SRS and OR. With a moderate addition of HA, U adsorption increased to near 100% at pH below 5.0. Because U partitioning onto the HA modified mineral surfaces is so strong, U concentration in groundwaters can be sustainably reduced to below its MCL. We conducted flow through experiments for U desorption by acidic groundwater leaching at pH 3.5 and 4.5 from HA-treated SRS contaminated sediments. The results show that desorption of both U

Hydroquinone-induced FOXP3-ADAM17-Lyn-Akt-p21 signaling axis promotes malignant progression of human leukemia U937 cells.

PubMed

Chen, Ying-Jung; Liu, Wen-Hsin; Chang, Long-Sen

2017-02-01

Hydroquinone (1,4-benzenediol; HQ), a major marrow metabolite of the leukemogen benzene, has been proven to evoke benzene-related hematological disorders and myelotoxicity in vitro and in vivo. The goal of the present study was to explore the role of FOXP3 in HQ-induced malignant progression of U937 human leukemia cells. U937 cells were treated with 5 μM HQ for 24 h, and the cells were re-suspended in serum-containing medium without HQ for 2 days. The same procedure was repeated three times, and the resulting U937/HQ cells were maintained in cultured medium containing 5 μM HQ. Proliferation and colony formation of U937/HQ cells were notably higher than those of U937 cells. Ten-eleven translocation methylcytosine dioxygenase-mediated demethylation of the Treg-specific demethylated region in FOXP3 gene resulted in higher FOXP3 expression in U937/HQ cells than in U937 cells. FOXP3-induced miR-183 expression reduced β-TrCP mRNA stability and suppressed β-TrCP-mediated Sp1 degradation, leading to up-regulation of Sp1 expression in U937/HQ cells. Sp1 up-regulation further increased ADAM17 and Lyn expression, and ADAM17 up-regulation stimulated Lyn activation in U937/HQ cells. Moreover, U937/HQ cells showed higher Lyn-mediated Akt activation and cytoplasmic p21 expression than U937 cells did. Abolishment of Akt activation decreased cytoplasmic p21 expression in U937/HQ cells. Suppression of FOXP3, ADAM17, and Lyn expression, as well as Akt inactivation, repressed proliferation and clonogenicity of U937/HQ cells. Together with the finding that cytoplasmic p21 shows anti-apoptotic and oncogenic activities in cancer cells, the present data suggest a role of FOXP3/ADAM17/Lyn/Akt/p21 signaling axis in HQ-induced hematological disorders.

Repeatability of a 3D multi-segment foot model protocol in presence of foot deformities.

PubMed

Deschamps, Kevin; Staes, Filip; Bruyninckx, Herman; Busschots, Ellen; Matricali, Giovanni A; Spaepen, Pieter; Meyer, Christophe; Desloovere, Kaat

2012-07-01

Repeatability studies on 3D multi-segment foot models (3DMFMs) have mainly considered healthy participants which contrasts with the widespread application of these models to evaluate foot pathologies. The current study aimed at establishing the repeatability of the 3DMFM described by Leardini et al. in presence of foot deformities. Foot kinematics of eight adult participants were analyzed using a repeated-measures design including two therapists with different levels of experience. The inter-trial variability was higher compared to the kinematics of healthy subjects. Consideration of relative angles resulted in the lowest inter-session variability. The absolute 3D rotations between the Sha-Cal and Cal-Met seem to have the lowest variability in both therapists. A general trend towards higher σ(sess)/σ(trial) ratios was observed when the midfoot was involved. The current study indicates that not only relative 3D rotations and planar angles can be measured consistently in patients, also a number of absolute parameters can be consistently measured serving as basis for the decision making process. Copyright © 2012 Elsevier B.V. All rights reserved.

Enhanced U(VI) release from autunite mineral by aerobic Arthrobacter sp. in the presence of aqueous bicarbonate

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

Katsenovich, Yelena P.; Carvajal, Denny A.; Wellman, Dawn M.

2012-05-01

The bacterial effect on U(VI) release from the autunite mineral (Ca[(UO2)(PO4)]2•3H2O) was investigated to provide a more comprehensive understanding of the important microbiological processes affecting autunite stability within subsurface bicarbonate-bearing environments. Experiments were performed in a culture of the Arthrobacter oxydans G975 strain, herein referred to as G975, a soil bacterium previously isolated from Hanford Site soil. 91 mg of autunite powder and 50 mL of phosphorous-limiting sterile media were amended with bicarbonate (ranging between 1 and 10 mM) in glass reactor bottles and inoculated with the G975 strain after the dissolution of autunite was at steady state. SEM observationsmore » indicated that G975 formed a biofilm on the autunite surface and penetrated the mineral cleavages. The mineral surface colonization by bacteria tended to increase concomitantly with bicarbonate concentrations. Additionally, a sterile culture-ware with inserts was used in non-contact dissolution experiments where autunite and bacteria cells were kept separately. The data suggest that G975 bacteria is able to enhance the release of U(VI) from autunite without direct contact with the mineral. In the presence of bicarbonate, the damage to bacterial cells caused by U(VI) toxicity was reduced, yielding similar values for total organic carbon (TOC) degradation and cell density compared to U(VI)-free controls. The presence of active bacterial cells greatly enhanced the release of U(VI) from autunite in bicarbonate-amended media.« less

Enhanced U(VI) release from autunite mineral by aerobic Arthrobacter sp. in the presence of aqueous bicarbonate

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

Katsenovich, Yelena; Carvajal, Denny A.; Wellman, Dawn M.

2012-04-20

The bacterial effect on U(VI) leaching from the autunite mineral (Ca[(UO{sub 2})(PO{sub 4})]{sub 2} {center_dot} 3H{sub 2}O) was investigated to provide a more comprehensive understanding into important microbiological processes affecting autunite stability within subsurface bicarbonate-bearing environments. Experiments were performed in a culture of G975 Arthrobacter oxydans strain, herein referred to as G975, a soil bacterium previously isolated from Hanford Site soil. 91 mg of autunite powder and 50 mL of phosphorus-limiting sterile media were amended with bicarbonate ranging between 1-10 mM in glass reactor bottles and inoculated with G975 strain after the dissolution of autunite was at steady state. SEMmore » observations indicated G975 formed a biofilm on the autunite surface and penetrated the mineral cleavages. The mineral surface colonization by bacteria tended to increase concomitantly with bicarbonate concentrations. Additionally, a sterile cultureware with inserts was used in non-contact bioleaching experiments where autunite and bacteria cells were kept separately. The data suggest the G975 bacteria is able to enhance U(VI) leaching from autunite without the direct contact with the mineral. In the presence of bicarbonate, the damage to bacterial cells caused by U(VI) toxicity was reduced, yielding similar values for total organic carbon (TOC) degradation and cell density compared to U(VI)-free controls. The presence of active bacterial cells greatly enhanced the U(VI) bioleaching from autunite in bicarbonate-amended media.« less

Multiple injection mode with or without repeated sample injections: Strategies to enhance productivity in countercurrent chromatography.

PubMed

Müller, Marco; Wasmer, Katharina; Vetter, Walter

2018-06-29

Countercurrent chromatography (CCC) is an all liquid based separation technique typically used for the isolation and purification of natural compounds. The simplicity of the method makes it easy to scale up CCC separations from analytical to preparative and even industrial scale. However, scale-up of CCC separations requires two different instruments with varying coil dimensions. Here we developed two variants of the CCC multiple injection mode as an alternative to increase the throughput and enhance productivity of a CCC separation when using only one instrument. The concept is based on the parallel injection of samples at different points in the CCC column system and the simultaneous separation using one pump only. The wiring of the CCC setup was modified by the insertion of a 6-port selection valve, multiple T-pieces and sample loops. Furthermore, the introduction of storage sample loops enabled the CCC system to be used with repeated injection cycles. Setup and advantages of both multiple injection modes were shown by the isolation of the furan fatty acid 11-(3,4-dimethyl-5-pentylfuran-2-yl)-undecanoic acid (11D5-EE) from an ethyl ester oil rich in 4,7,10,13,16,19-docosahexaenoic acid (DHA-EE). 11D5-EE was enriched in one step from 1.9% to 99% purity. The solvent consumption per isolated amount of analyte could be reduced by ∼40% compared to increased throughput CCC and by ∼5% in the repeated multiple injection mode which also facilitated the isolation of the major compound (DHA-EE) in the sample. Copyright © 2018 Elsevier B.V. All rights reserved.

Fostering repeat donations in Ghana.

PubMed

Owusu-Ofori, S; Asenso-Mensah, K; Boateng, P; Sarkodie, F; Allain, J-P

2010-01-01

Most African countries are challenged in recruiting and retaining voluntary blood donors by cost and other complexities and in establishing and implementing national blood policies. The availability of replacement donors who are a cheaper source of blood has not enhanced repeat voluntary donor initiatives. An overview of activities for recruiting and retaining voluntary blood donors was carried out. Donor records from mobile sessions were reviewed from 2002 to 2008. A total of 71,701 blood donations; 45,515 (63.5%) being voluntary donations with 11,680 (25%) repeat donations were collected during the study period. Donations from schools and colleges contributed a steady 60% of total voluntary whilst radio station blood drives increased contribution from 10 to 27%. Though Muslim population is less than 20%, blood collection was above the 30-donation cost-effectiveness threshold with a repeat donation trend reaching 60%. In contrast Christian worshippers provided <25 unit/session and 30% repeat donations. Repeat donation trends amongst school donors and radio blood drives were 20% and 70% respectively. Repeat donations rates have been variable amongst different blood donor groups in Kumasi, Ghana. The impact of community leaders in propagating altruism cannot be overemphasized. Programs aiming at motivating replacement donors to be repeat donors should be developed and assessed. Copyright 2009 The International Association for Biologicals. All rights reserved.

An Enhanced Seasonal Transition that Intensified Summer Drought in the Central U.S.

NASA Technical Reports Server (NTRS)

Wang, S.-Y.Simon; Santanello, Joseph; Wang, Hailan; Barandiaran, Daniel; Pinker, Rachel; Schubert, Siegfried; Gillies, Robert R.; Oglesby, Robert; Hilburn, Kyle; Kilic, Ayse;

The mismatch repair system protects against intergenerational GAA repeat instability in a Friedreich ataxia mouse model.

PubMed

Ezzatizadeh, Vahid; Pinto, Ricardo Mouro; Sandi, Chiranjeevi; Sandi, Madhavi; Al-Mahdawi, Sahar; Te Riele, Hein; Pook, Mark A

2012-04-01

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by a dynamic GAA repeat expansion mutation within intron 1 of the FXN gene. Studies of mouse models for other trinucleotide repeat (TNR) disorders have revealed an important role of mismatch repair (MMR) proteins in TNR instability. To explore the potential role of MMR proteins on intergenerational GAA repeat instability in FRDA, we have analyzed the transmission of unstable GAA repeat expansions from FXN transgenic mice which have been crossed with mice that are deficient for Msh2, Msh3, Msh6 or Pms2. We find in all cases that absence of parental MMR protein not only maintains transmission of GAA expansions and contractions, but also increases GAA repeat mutability (expansions and/or contractions) in the offspring. This indicates that Msh2, Msh3, Msh6 and Pms2 proteins are not the cause of intergenerational GAA expansions or contractions, but act in their canonical MMR capacity to protect against GAA repeat instability. We further identified differential modes of action for the four MMR proteins. Thus, Msh2 and Msh3 protect against GAA repeat contractions, while Msh6 protects against both GAA repeat expansions and contractions, and Pms2 protects against GAA repeat expansions and also promotes contractions. Furthermore, we detected enhanced occupancy of Msh2 and Msh3 proteins downstream of the FXN expanded GAA repeat, suggesting a model in which Msh2/3 dimers are recruited to this region to repair mismatches that would otherwise produce intergenerational GAA contractions. These findings reveal substantial differences in the intergenerational dynamics of expanded GAA repeat sequences compared with expanded CAG/CTG repeats, where Msh2 and Msh3 are thought to actively promote repeat expansions. Copyright © 2012 Elsevier Inc. All rights reserved.

The mismatch repair system protects against intergenerational GAA repeat instability in a Friedreich ataxia mouse model

PubMed Central

Ezzatizadeh, Vahid; Pinto, Ricardo Mouro; Sandi, Chiranjeevi; Sandi, Madhavi; Al-Mahdawi, Sahar; te Riele, Hein; Pook, Mark A.

2013-01-01

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by a dynamic GAA repeat expansion mutation within intron 1 of the FXN gene. Studies of mouse models for other trinucleotide repeat (TNR) disorders have revealed an important role of mismatch repair (MMR) proteins in TNR instability. To explore the potential role of MMR proteins on intergenerational GAA repeat instability in FRDA, we have analyzed the transmission of unstable GAA repeat expansions from FXN transgenic mice which have been crossed with mice that are deficient for Msh2, Msh3, Msh6 or Pms2. We find in all cases that absence of parental MMR protein not only maintains transmission of GAA expansions and contractions, but also increases GAA repeat mutability (expansions and/or contractions) in the offspring. This indicates that Msh2, Msh3, Msh6 and Pms2 proteins are not the cause of intergenerational GAA expansions or contractions, but act in their canonical MMR capacity to protect against GAA repeat instability. We further identified differential modes of action for the four MMR proteins. Thus, Msh2 and Msh3 protect against GAA repeat contractions, while Msh6 protects against both GAA repeat expansions and contractions, and Pms2 protects against GAA repeat expansions and also promotes contractions. Furthermore, we detected enhanced occupancy of Msh2 and Msh3 proteins downstream of the FXN expanded GAA repeat, suggesting a model in which Msh2/3 dimers are recruited to this region to repair mismatches that would otherwise produce intergenerational GAA contractions. These findings reveal substantial differences in the intergenerational dynamics of expanded GAA repeat sequences compared with expanded CAG/CTG repeats, where Msh2 and Msh3 are thought to actively promote repeat expansions. PMID:22289650

Repeatability and correlations of dynamic contrast enhanced and T2* MRI in patients with advanced pancreatic ductal adenocarcinoma.

PubMed

Klaassen, Remy; Gurney-Champion, Oliver J; Wilmink, Johanna W; Besselink, Marc G; Engelbrecht, Marc R W; Stoker, Jaap; Nederveen, Aart J; van Laarhoven, Hanneke W M

2018-07-01

In current oncological practice of pancreatic ductal adenocarcinoma (PDAC), there is a great demand for response predictors and markers for early treatment evaluation. In this study, we investigated the repeatability and the interaction of dynamic contrast enhanced (DCE) and T2* MRI in patients with advanced PDAC to enable for such evaluation using these techniques. 15 PDAC patients underwent two DCE, T2* and anatomical 3 T MRI sessions before start of treatment. Parametric maps were calculated for the transfer constant (K trans ), rate constant (k ep ), extracellular extravascular space (v e ) and perfusion fraction (v p ). Quantitative R2* (1/T2*) maps were obtained from the multi-echo T2* images. Differences between normal and cancerous pancreas were determined using a Wilcoxon matched pairs test. Repeatability was obtained using Bland-Altman analysis and relations between DCE and T2*/R2* were observed by Spearman correlation and voxel-wise binned plots of tumor voxels. PDAC K trans (p = 0.007), k ep (p < 0.001), v p (p = 0.035) were lower and v e (p < 0.001) was higher compared to normal pancreas. The coefficient of variation between sessions was 21.8% for K trans , 9.9% for k ep , 19.3% for v e , 18.2% for v p and 18.7% for R2*. Variation between patients ranged from 20.2% for k ep to 43.6% for K trans . In the tumor both K trans (r = 0.56, p = 0.030) and v e (r = 0.54, p = 0.037) showed a positive correlation with T2*. Voxel wise analysis showed a steep increase in R2* for tumor voxels with lower K trans and v e . We showed good repeatability of DCE and T2* related MRI parameters in advanced PDAC patients. Furthermore, we have illustrated the relation of DCE K trans and v e with tissue T2* and R2* indicating substantial value of these parameters for detecting tumor hypoxia in future studies. The results from our study pave the way for further response evaluation studies and patient selection based on DCE and T2* parameters

Population genetics and new insight into range of CAG repeats of spinocerebellar ataxia type 3 in the Han Chinese population.

PubMed

Gan, Shi-Rui; Ni, Wang; Dong, Yi; Wang, Ning; Wu, Zhi-Ying

2015-01-01

Spinocerebellar ataxia type 3 (SCA3), also called Machado-Joseph disease (MJD), is one of the most common SCAs worldwide and caused by a CAG repeat expansion located in ATXN3 gene. Based on the CAG repeat numbers, alleles of ATXN3 can be divided into normal alleles (ANs), intermediate alleles (AIs) and expanded alleles (AEs). It was controversial whether the frequency of large normal alleles (large ANs) is related to the prevalence of SCA3 or not. And there were huge chaos in the comprehension of the specific numbers of the range of CAG repeats which is fundamental for genetic analysis of SCA3. To illustrate these issues, we made a novel CAG repeat ladder to detect CAG repeats of ATXN3 in 1003 unrelated Chinese normal individuals and studied haplotypes defined by three single nucleotide polymorphisms (SNPs) closed to ATXN3. We found that the number of CAG repeats ranged from 13 to 49, among them, 14 was the most common number. Positive skew, the highest frequency of large ANs and 4 AIs which had never been reported before were found. Also, AEs and large ANs shared the same haplotypes defined by the SNPs. Based on these data and other related studies, we presumed that de novo mutations of ATXN3 emerging from large ANs are at least one survival mechanisms of mutational ATXN3 and we can redefine the range of CAG repeats as: ANs≤44, 45 ≤AIs ≤49 and AEs≥50.

Structure of an E3:E2~Ub Complex Reveals an Allosteric Mechanism Shared among RING/U-box Ligases

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

Pruneda, Jonathan N.; Littlefield, Peter J.; Soss, Sarah E.

2012-09-28

Despite the widespread importance of RING/U-box E3 ubiquitin ligases in ubiquitin (Ub) signaling, the mechanismby which this class of enzymes facilitates Ub transfer remains enigmatic. Here, we present a structural model for a RING/U-box E3:E2~Ub complex poised for Ub transfer. The model and additional analyses reveal that E3 binding biases dynamic E2~Ub ensembles toward closed conformations with enhanced reactivity for substrate lysines. We identify a key hydrogen bond between a highly conserved E3 side chain and an E2 backbone carbonyl, observed in all structures of active RING/ U-Box E3/E2 pairs, as the linchpin for allosteric activation of E2~Ub. The conformationalmore » biasing mechanism is generalizable across diverse E2s and RING/U-box E3s, but is not shared by HECT-type E3s. The results provide a structural model for a RING/ U-box E3:E2~Ub ligase complex and identify the long sought-after source of allostery for RING/UBox activation of E2~Ub conjugates.« less

The Theoretical Transition Probabilities Between the B(sup 3)Pi(sub g) and the A(sup 3)Sigma(Sup +, sub u), W(sup 3)Delta(sub u), B'(sup 3)Sigma(sup -, sub u) States of N2

NASA Technical Reports Server (NTRS)

Thuemmel, Helmar T.; Partridge, Harry; Huo, Winifred M.; Langhoff, Stephen (Technical Monitor)

1995-01-01

The electronic transition moment functions between the B(sup 3)Pi(sub g) and the A(sup 3)Sigma(sup +, sub u), W(sup 3)Delta(sub u), B'(sup 3)Sigma(sup -, sub u) states of N2 are studied using the internally contracted multireference configuration interaction (ICMRCI) method based upon complete active space SCF (CASSCF) reference wave-functions. The dependence of the moments on both the one and n-particle basis sets has been investigated in detail. The calculated radiative lifetimes for the vibrational levels of B(sup 3)Pi(sub g) are in excellent agreement with the most recent measurement of Euler and Pipkin (1983)

Security of Quantum Repeater Network Operation

DTIC Science & Technology

2016-10-03

AFRL-AFOSR-JP-TR-2016-0079 Security of Quantum Repeater Network Operation Rodney Van Meter KEIO UNIVERSITY Final Report 10/03/2016 DISTRIBUTION A...To)  29 May 2014 to 28 May 2016 4. TITLE AND SUBTITLE Security of Quantum Repeater Network Operation 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA2386...ABSTRACT Much of the work on quantum networks , both entangled and unentangled, has been about the uses of quantum networks to enhance end- host security

hnRNP L binds to CA repeats in the 3'UTR of bcl-2 mRNA

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

Lee, Dong-Hyoung; Lim, Mi-Hyun; Youn, Dong-Ye

We previously reported that the CA-repeat sequence in the 3'-untranslated region (3'UTR) of bcl-2 mRNA is involved in the decay of bcl-2 mRNA. However, the trans-acting factor for the CA element in bcl-2 mRNA remains unidentified. The heterogeneous nuclear ribonucleoprotein L (hnRNP L), an intron splicing factor, has been reported to bind to CA repeats and CA clusters in the 3'UTR of several genes. We reported herein that the CA repeats of bcl-2 mRNA have the potential to form a distinct ribonuclear protein complex in cytoplasmic extracts of MCF-7 cells, as evidenced by RNA electrophoretic mobility shift assays (REMSA). Amore » super-shift assay using the hnRNP L antibody completely shifted the complex. Immunoprecipitation with the hnRNP L antibody and MCF-7 cells followed by RT-PCR revealed that hnRNP L interacts with endogenous bcl-2 mRNA in vivo. Furthermore, the suppression of hnRNP L in MCF-7 cells by the transfection of siRNA for hnRNP L resulted in a delay in the degradation of RNA transcripts including CA repeats of bcl-2 mRNA in vitro, suggesting that the interaction between hnRNPL and CA repeats of bcl-2 mRNA participates in destabilizing bcl-2 mRNA.« less

Enhanced central serotonin release from slices of rat hypothalamus following repeated nialamide administration: evidence supporting the overactive serotonin receptor theory of depression

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

Offord, S.J.

1986-01-01

Researchers are suggesting unipolar affective disorders may be related to an abnormality in biogenic amine receptor-sensitivity. This abnormality may be a result of a dysfunction in central serotonin (5-HT) release mechanisms. 5-HT neurotransmission is modulated by presynaptic autoreceptors, which are members of the 5-HT/sub 1/ receptor subtype. The autoreceptor is thought to play an important role in the homeostasis of the central 5-HT synapse and could be a site at which some antidepressants mediate their therapeutic effect. The number of 5-HT/sub 1/ type receptor binding sites are reduced and behavior mediated by this receptor is abolished following repeated injections ofmore » monoamine oxidase inhibitor type antidepressants. These changes did not occur following a single injection. It was hypothesized that repeated treatment with a monoamine oxidase inhibitor would reduce the sensitivity of 5-HT autoreceptors and enhance 5-HT release. Rats were pretreated with single or repeated (twice daily for 7 days) intraperitoneal injections of nialamide (40 mg/kg) or chlorimipramine (10 mg/kg) and the ability of the autoreceptor agonist to inhibit potassium-induced /sup 3/H-5-HT release was evaluated using an in vitro superfusion system. These changes in 5-HT autoreceptor activity are consistent with other reports evaluating monoamine oxidase inhibitors on 5-HT/sub 1/ type receptors. It is hypothesized that the changes in 5-HT neurotransmission are related to the antidepressant mechanism of monoamine oxidase inhibitors.« less

Control of trichome formation in Arabidopsis by poplar single-repeat R3 MYB transcription factors

PubMed Central

Zhou, Limei; Zheng, Kaijie; Wang, Xiaoyu; Tian, Hainan; Wang, Xianling; Wang, Shucai

2014-01-01

In Arabidopsis, trichome formation is regulated by the interplay of R3 MYBs and several others transcription factors including the WD40-repeat protein TRANSPARENT TESTA GLABRA1 (TTG1), the R2R3 MYB transcription factor GLABRA1 (GL1), the bHLH transcription factor GLABRA3 (GL3) or ENHANCER OF GLABRA3 (EGL3), and the homeodomain protein GLABRA2 (GL2). R3 MYBs including TRICHOMELESS1 (TCL1), TCL2, TRYPTICHON (TRY), CAPRICE (CPC), ENHANCER OF TRY AND CPC1 (ETC1), ETC2 and ETC3 negatively regulate trichome formation by competing with GL1 for binding GL3 or EGL3, thus blocking the formation of TTG1–GL3/EGL3–GL1, an activator complex required for the activation of the trichome positive regulator gene GL2. However, it is largely unknown if R3 MYBs in other plant species especially woody plants have similar functions. By BLASTing the Populus trichocarpa protein database using the entire amino acid sequence of TCL1, an Arabidopsis R3 MYB transcription factor, we identified a total of eight R3 MYB transcription factor genes in poplar, namely P. trichocarpa TRICHOMELESS1 through 8 (PtrTCL1–PtrTCL8). The amino acid signature required for interacting with bHLH transcription factors and the amino acids required for cell-to-cell movement of R3 MYBs are not fully conserved in all PtrTCLs. When tested in Arabidopsis protoplasts, however, all PtrTCLs interacted with GL3. Expressing each of the eight PtrTCL genes in Arabidopsis resulted in either glabrous phenotypes or plants with reduced trichome numbers, and expression levels of GL2 in all transgenic plants tested were greatly reduced. Expression of PtrTCL1 under the control of TCL1 native promoter almost completely complemented the mutant phenotype of tcl. In contrast, expression of PtrTCL1 under the control of TRY native promoter in the try mutant, or under the control of CPC native promoter in the cpc mutant resulted in glabrous phenotypes, suggesting that PtrTCL1 functions similarly to TCL1, but not TRY and CPC. PMID

Regulation of cell fate determination by single-repeat R3 MYB transcription factors in Arabidopsis

PubMed Central

Wang, Shucai; Chen, Jin-Gui

2014-01-01

MYB transcription factors regulate multiple aspects of plant growth and development. Among the large family of MYB transcription factors, single-repeat R3 MYBs are characterized by their short sequence (<120 amino acids) consisting largely of the single MYB DNA-binding repeat. In the model plant Arabidopsis, R3 MYBs mediate lateral inhibition during epidermal patterning and are best characterized for their regulatory roles in trichome and root hair development. R3 MYBs act as negative regulators for trichome formation but as positive regulators for root hair development. In this article, we provide a comprehensive review on the role of R3 MYBs in the regulation of cell type specification in the model plant Arabidopsis. PMID:24782874

Minimal S U ( 3 ) × S U ( 3 ) symmetry breaking patterns

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

Bai, Yang; Dobrescu, Bogdan A.

Here, we study the vacua of anmore » $$SU(3)\\times SU(3)$$-symmetric model with a bifundamental scalar. Structures of this type appear in various gauge theories such as the Renormalizable Coloron Model, which is an extension of QCD, or the Trinification extension of the electroweak group. In other contexts, such as chiral symmetry, $$SU(3)\\times SU(3)$$ is a global symmetry. As opposed to more general $$SU(N)\\times SU(N)$$ symmetric models, the $N=3$ case is special due to the presence of a trilinear scalar term in the potential. We find that the most general tree-level potential has only three types of minima: one that preserves the diagonal $SU(3)$ subgroup, one that is $$SU(2)\\times SU(2)\\times U(1)$$ symmetric, and a trivial one where the full symmetry remains unbroken. The phase diagram is complicated, with some regions where there is a unique minimum, and other regions where two minima coexist.« less

Minimal S U ( 3 ) × S U ( 3 ) symmetry breaking patterns

DOE PAGES

Bai, Yang; Dobrescu, Bogdan A.

2018-03-16

Here, we study the vacua of anmore » $$SU(3)\\times SU(3)$$-symmetric model with a bifundamental scalar. Structures of this type appear in various gauge theories such as the Renormalizable Coloron Model, which is an extension of QCD, or the Trinification extension of the electroweak group. In other contexts, such as chiral symmetry, $$SU(3)\\times SU(3)$$ is a global symmetry. As opposed to more general $$SU(N)\\times SU(N)$$ symmetric models, the $N=3$ case is special due to the presence of a trilinear scalar term in the potential. We find that the most general tree-level potential has only three types of minima: one that preserves the diagonal $SU(3)$ subgroup, one that is $$SU(2)\\times SU(2)\\times U(1)$$ symmetric, and a trivial one where the full symmetry remains unbroken. The phase diagram is complicated, with some regions where there is a unique minimum, and other regions where two minima coexist.« less

Effects of the nitric oxide donor JS-K on the blood-tumor barrier and on orthotopic U87 rat gliomas assessed by MRI

PubMed Central

Weidensteiner, Claudia; Reichardt, Wilfried; Shami, Paul J.; Saavedra, Joseph E.; Keefer, Larry K.; Baumer, Brunhilde; Werres, Anna; Jasinski, Robert; Osterberg, Nadja; Weyerbrock, Astrid

2013-01-01

Nitric oxide (NO) released from NO donors can be cytotoxic in tumor cells and can enhance the transport of drugs into brain tumors by altering blood-tumor barrier permeability. The NO donor JS-K [O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] releases NO upon enzymatic activation selectively in cells overexpressing glutathione-S-transferases (GSTs) such as gliomas. Thus, JS-K-dependent NO effects - especially on cell viability and vascular permeability - were investigated in U87 glioma cells in vitro and in an orthotopic U87 xenograft model in vivo by magnetic resonance imaging (MRI). In vitro experiments showed dose-dependent antiproliferative and cytotoxic effects in U87 cells. In addition, treatment of U87 cells with JS-K resulted in a dose-dependent activation of soluble guanylate cyclase and intracellular accumulation of cyclic guanosine monophosphate (cGMP) which was irreversibly inhibited by the selective inhibitor of soluble guanylate cyclase ODQ (1H-[1,2,4]oxadiazolo(4,3a)quinoxaline-1-one). Using dynamic contrast enhanced MRI (DCE-MRI) as a minimally invasive technique, we demonstrated for the first time a significant increase in the DCE-MRI read-out initial area under the concentration curve (iAUC60) indicating an acute increase in blood-tumor barrier permeability after i.v. treatment with JS-K. Repeated MR imaging of animals with intracranial U87 gliomas under treatment with JS-K (3.5 μmol/kg JS-K 3×/week) and of untreated controls on day 12 and 19 after tumor inoculation revealed no significant changes in tumor growth, edema formation or tumor perfusion. Immunohistochemical workup of the brains showed a significant antiproliferative effect of JS-K in the gliomas. Taken together, in vitro and in vivo data suggest that JS-K has antiproliferative effects in U87 gliomas and opens the blood-tumor barrier by activation of the NO/cGMP signaling pathway. This might be a novel approach to facilitate entry of therapeutic

Effects of the nitric oxide donor JS-K on the blood-tumor barrier and on orthotopic U87 rat gliomas assessed by MRI.

PubMed

Weidensteiner, Claudia; Reichardt, Wilfried; Shami, Paul J; Saavedra, Joseph E; Keefer, Larry K; Baumer, Brunhilde; Werres, Anna; Jasinski, Robert; Osterberg, Nadja; Weyerbrock, Astrid

2013-04-01

Nitric oxide (NO) released from NO donors can be cytotoxic in tumor cells and can enhance the transport of drugs into brain tumors by altering blood-tumor barrier permeability. The NO donor JS-K [O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] releases NO upon enzymatic activation selectively in cells overexpressing glutathione-S-transferases (GSTs) such as gliomas. Thus, JS-K-dependent NO effects - especially on cell viability and vascular permeability - were investigated in U87 glioma cells in vitro and in an orthotopic U87 xenograft model in vivo by magnetic resonance imaging (MRI). In vitro experiments showed dose-dependent antiproliferative and cytotoxic effects in U87 cells. In addition, treatment of U87 cells with JS-K resulted in a dose-dependent activation of soluble guanylate cyclase and intracellular accumulation of cyclic guanosine monophosphate (cGMP) which was irreversibly inhibited by the selective inhibitor of soluble guanylate cyclase ODQ (1H-[1,2,4]oxadiazolo(4,3a)quinoxaline-1-one). Using dynamic contrast enhanced MRI (DCE-MRI) as a minimally invasive technique, we demonstrated for the first time a significant increase in the DCE-MRI read-out initial area under the concentration curve (iAUC60) indicating an acute increase in blood-tumor barrier permeability after i.v. treatment with JS-K. Repeated MR imaging of animals with intracranial U87 gliomas under treatment with JS-K (3.5 μmol/kg JS-K 3×/week) and of untreated controls on day 12 and 19 after tumor inoculation revealed no significant changes in tumor growth, edema formation or tumor perfusion. Immunohistochemical workup of the brains showed a significant antiproliferative effect of JS-K in the gliomas. Taken together, in vitro and in vivo data suggest that JS-K has antiproliferative effects in U87 gliomas and opens the blood-tumor barrier by activation of the NO/cGMP signaling pathway. This might be a novel approach to facilitate entry of therapeutic

Differential cross sections for the electron impact excitation of the A {sup 3}{sigma}{sub u}{sup +}, B {sup 3}{pi}{sub g}, W {sup 3}{delta}{sub u}, B{sup '} {sup 3}{sigma}{sub u}{sup -}, a{sup '} {sup 1}{sigma}{sub u}{sup -}, a {sup 1}{pi}{sub g}, w {sup 1}{delta}{sub u}, and C {sup 3}{pi}{sub u} states of N{sub 2}

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

Khakoo, M.A.; Ozkay, I.; Johnson, P.V.

2005-06-15

Measurements of differential cross sections for the electron-impact excitation of molecular nitrogen from the ground X {sup 1}{sigma}{sub g}{sup +}(v{sup ''}=0) level to the A {sup 3}{sigma}{sub u}{sup +}(v{sup '}), B {sup 3}{pi}{sub g}(v{sup '}), W {sup 3}{delta}{sub u}(v{sup '}), B{sup '} {sup 3}{sigma}{sub u}{sup -}(v{sup '}), a{sup '} {sup 1}{sigma}{sub u}{sup -}(v{sup '}), a {sup 1}{pi}{sub g}(v{sup '}), w {sup 1}{delta}{sub u}(v{sup '}), and C {sup 3}{pi}{sub u}(v{sup '}) levels are presented. The data are obtained at the incident energies of 10, 12.5, 15, 17.5, 20, 30, 50, and 100 eV over the angular range of 5 deg. -130more » deg. in 5 deg. intervals. The individual electronic state excitation differential cross sections are obtained by unfolding electron energy-loss spectra of molecular nitrogen using available semiempirical Frank-Condon factors. The data are compared to previous measurements and to available theory. We also make several important suggestions regarding future work that, like the present, relies on the unfolding of electron energy-loss spectra for obtaining differential cross sections.« less

X-Ray Enhancement and Long-term Evolution of Swift J1822.3-1606

NASA Astrophysics Data System (ADS)

Benli, Onur; Çalışkan, Ş.; Ertan, Ü.; Alpar, M. A.; Trümper, J. E.; Kylafis, N. D.

2013-12-01

We investigate the X-ray enhancement and the long-term evolution of the recently discovered second "low-B magnetar" Swift J1822.3-1606 in the frame of the fallback disk model. During a soft gamma burst episode, the inner disk matter is pushed back to larger radii, forming a density gradient at the inner disk. Subsequent relaxation of the inner disk could account for the observed X-ray enhancement light curve of Swift J1822.3-1606. We obtain model fits to the X-ray data with basic disk parameters similar to those employed to explain the X-ray outburst light curves of other anomalous X-ray pulsars and soft gamma repeaters. The long period (8.4 s) of the neutron star can be reached by the effect of the disk torques in the long-term accretion phase ((1-3) × 105 yr). The currently ongoing X-ray enhancement could be due to a transient accretion epoch, or the source could still be in the accretion phase in quiescence. Considering these different possibilities, we determine the model curves that could represent the long-term rotational and the X-ray luminosity evolution of Swift J1822.3-1606, which constrain the strength of the magnetic dipole field to the range of (1-2) × 1012 G on the surface of the neutron star.

Bioreduction of U(VI)-Phthalate to a Polymeric U(IV)-Phthalate Colloid

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

Vazquez, G.; Dodge, C; Francis, A

2009-01-01

Phthalic acid, a ubiquitous organic ligand, formed soluble mono- and biligand complexes with a uranyl ion that was then reduced to a U(IV)-phthalate by a Clostridium species under anaerobic conditions. We confirmed the reduction of the hexavalent uranium to the tetravalent oxidation state by UV-vis absorption and X-ray absorption near edge structure spectroscopy. Sequential micro- and ultrafiltration of the solution revealed that the bioreduced uranium was present as a colloid with particles between 0.03 and 0.45 {mu}m. Analysis with extended X-ray absorption fine structure revealed the association of the reduced uranium with the phthalic acid as a repeating biligand 1:2more » U(IV):phthalic acid polymer. This is the first report of the formation of a U(IV) complexed to two phthalic acid molecules in the form of a polymeric colloid. Although it was proposed that the bioreduction and the precipitation of uranium might be an invaluable strategy to immobilize uranium in contaminated environments, our results suggest that the organic ligands present there might hinder the precipitation of the bioreduced uranium under anaerobic conditions and, thereby, enhance its environmental mobility as uranium organic complexes or colloids.« less

Regulation of Cell Fate Determination by Single-Repeat R3 MYB Transcription Factors in Arabidopsis

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

Wang, Shucai; Chen, Jay

2014-01-01

MYB transcription factors regulate multiple aspects of plant growth and development. Among the large family of MYB transcription factors, single-repeat R3 MYB are characterized by their short sequence (<120 amino acids) consisting largely of the single MYB DNA-binding repeat. In the model plant Arabidopsis, R3 MYBs mediate lateral inhibition during epidermal patterning and are best characterized for their regulatory roles in trichome and root hair development. R3 MYBs act as negative regulators for trichome formation but as positive regulators for root hair development. In this article, we provide a comprehensive review on the role of R3 MYBs in the regulationmore » of cell type specification in the model plant Arabidopsis.« less

Mutation of the C/EBP binding sites in the Rous sarcoma virus long terminal repeat and gag enhancers.

PubMed Central

Ryden, T A; de Mars, M; Beemon, K

1993-01-01

Several C/EBP binding sites within the Rous sarcoma virus (RSV) long terminal repeat (LTR) and gag enhancers were mutated, and the effect of these mutations on viral gene expression was assessed. Minimal site-specific mutations in each of three adjacent C/EBP binding sites in the LTR reduced steady-state viral RNA levels. Double mutation of the two 5' proximal LTR binding sites resulted in production of 30% of wild-type levels of virus. DNase I footprinting analysis of mutant DNAs indicated that the mutations blocked C/EBP binding at the affected sites. Additional C/EBP binding sites were identified upstream of the 3' LTR and within the 5' end of the LTRs. Point mutations in the RSV gag intragenic enhancer region, which blocked binding of C/EBP at two of three adjacent C/EBP sites, also reduced virus production significantly. Nuclear extracts prepared from both chicken embryo fibroblasts (CEFs) and chicken muscle contained proteins binding to the same RSV DNA sites as did C/EBP, and mutations that prevented C/EBP binding also blocked binding of these chicken proteins. It appears that CEFs and chicken muscle contain distinct proteins binding to these RSV DNA sites; the CEF binding protein was heat stable, as is C/EBP, while the chicken muscle protein was heat sensitive. Images PMID:8386280

Comparative investigation of the solution species [U(CO3)5]6- and the crystal structure of Na6[U(CO3)5].12H2O.

PubMed

Hennig, Christoph; Ikeda-Ohno, Atsushi; Emmerling, Fanziska; Kraus, Werner; Bernhard, Gert

2010-04-21

The limiting U(IV) carbonate species in aqueous solution was investigated by comparing its structure parameters with those of the complex preserved in a crystal structure. The solution species prevails in aqueous solution of 0.05 M U(IV) and 1 M NaHCO(3) at pH 8.3. Single crystals of Na(6)[U(CO(3))(5)].12H(2)O were obtained directly from this mother solution. The U(IV) carbonate complex in the crystal structure was identified as a monomeric [U(CO(3))(5)](6-) anionic complex. The interatomic distances around the U(IV) coordination polyhedron show average distances of U-O = 2.461(8) A, U-C = 2.912(4) A and U-O(dist) = 4.164(6) A. U L(3)-edge EXAFS spectra were collected from the solid Na(6)[U(CO(3))(5)].12H(2)O and the corresponding solution. The first shell of the Fourier transforms (FTs) revealed, in both samples, a coordination of ten oxygen atoms at an average U-O distance of 2.45 +/- 0.02 A, the second shell originates from five carbon atoms with a U-C distance of 2.91 +/- 0.02 A, and the third shell was fit with single and multiple scattering paths of the distal oxygen at 4.17 +/- 0.02 A. These data indicate the identity of the [U(CO(3))(5)](6-) complex in solid and solution state. The high negative charge of the [U(CO(3))(5)](6-) anion is compensated by Na(+) cations. In solid state the Na(+) cations form a bridging network between the [U(CO(3))(5)](6-) units, while in liquid state the Na(+) cations seem to be located close to the anionic complex. The average metal-oxygen distances of the coordination polyhedron show a linear correlation to the radius contraction of the neighbouring actinide(IV) ions and indicate the equivalence of the [An(CO(3))(5)](6-) coordination within the series of thorium, uranium, neptunium and plutonium.

Enhanced nucleon transfer in tip collisions of 238U+124Sn

NASA Astrophysics Data System (ADS)

Sekizawa, Kazuyuki

2017-10-01

Multinucleon transfer processes in low-energy heavy ion reactions have attracted increasing interest in recent years aiming at the production of new neutron-rich isotopes. Clearly, it is an imperative task to further develop understanding of underlying reaction mechanisms to lead experiments to success. In this paper, from systematic time-dependent Hartree-Fock calculations for the 238U+124Sn reaction, it is demonstrated that transfer dynamics depend strongly on the orientations of 238U, quantum shells, and collision energies. Two important conclusions are obtained: (i) Experimentally observed many-proton transfer from 238U to 124Sn can be explained by a multinucleon transfer mechanism governed by enhanced neck evolution in tip collisions; (ii) novel reaction dynamics are observed in tip collisions at energies substantially above the Coulomb barrier, where a number of nucleons are transferred from 124Sn to 238U, producing transuranium nuclei as primary reaction products, which could be a means to synthesize superheavy nuclei. Both results indicate the importance of the neck (shape) evolution dynamics, which are sensitive to orientations, shell effects, and collision energies, for exploring possible pathways to produce new unstable nuclei.

Repeated Measurement of the Intermountain Risk Score Enhances Prognostication for Mortality

PubMed Central

Horne, Benjamin D.; Lappé, Donald L.; Muhlestein, Joseph B.; May, Heidi T.; Ronnow, Brianna S.; Brunisholz, Kimberly D.; Kfoury, Abdallah G.; Bunch, T. Jared; Alharethi, Rami; Budge, Deborah; Whisenant, Brian K.; Bair, Tami L.; Jensen, Kurt R.; Anderson, Jeffrey L.

2013-01-01

Background The Intermountain Risk Score (IMRS), composed of the complete blood count (CBC) and basic metabolic profile (BMP), predicts mortality and morbidity in medical and general populations. Whether longitudinal repeated measurement of IMRS is useful for prognostication is an important question for its clinical applicability. Methods Females (N = 5,698) and males (N = 5,437) with CBC and BMP panels measured 6 months to 2.0 years apart (mean 1.0 year) had baseline and follow-up IMRS computed. Survival analysis during 4.0±2.5 years (maximum 10 years) evaluated mortality (females: n = 1,255 deaths; males: n = 1,164 deaths) and incident major events (myocardial infarction, heart failure [HF], and stroke). Results Both baseline and follow-up IMRS (categorized as high-risk vs. low-risk) were independently associated with mortality (all p<0.001) in bivariable models. For females, follow-up IMRS had hazard ratio (HR) = 5.23 (95% confidence interval [CI] = 4.11, 6.64) and baseline IMRS had HR = 3.66 (CI = 2.94, 4.55). Among males, follow-up IMRS had HR = 4.28 (CI = 3.51, 5.22) and baseline IMRS had HR = 2.32 (CI = 1.91, 2.82). IMRS components such as RDW, measured at both time points, also predicted mortality. Baseline and follow-up IMRS strongly predicted incident HF in both genders. Conclusions Repeated measurement of IMRS at baseline and at about one year of follow-up were independently prognostic for mortality and incident HF among initially hospitalized patients. RDW and other CBC and BMP values were also predictive of outcomes. Further research should evaluate the utility of IMRS as a tool for clinical risk adjustment. PMID:23874899

Newcastle disease virus triggers autophagy in U251 glioma cells to enhance virus replication.

PubMed

Meng, Chunchun; Zhou, Zhizhi; Jiang, Ke; Yu, Shengqing; Jia, Lijun; Wu, Yantao; Liu, Yanqing; Meng, Songshu; Ding, Chan

2012-06-01

Newcastle disease virus (NDV) can replicate in tumor cells and induce apoptosis in late stages of infection. However, the interaction between NDV and cells in early stages of infection is not well understood. Here, we report that, shortly after infection, NDV triggers the formation of autophagosomes in U251 glioma cells, as demonstrated by an increased number of double-membrane vesicles, GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) a dot formations, and elevated production of LC3II. Moreover, modulation of NDV-induced autophagy by rapamycin, chloroquine or small interfering RNAs targeting the genes critical for autophagosome formation (Atg5 and Beclin-1) affects virus production, indicating that autophagy may be utilized by NDV to facilitate its own production. Furthermore, the class III phosphatidylinositol 3-kinase (PI3K)/Beclin-1 pathway plays a role in NDV-induced autophagy and virus production. Collectively, our data provide a unique example of a paramyxovirus that uses autophagy to enhance its production.

The Importance of the Study of Cognitive Performance Enhancement for U.S. National Security.

PubMed

Malish, Richard G

2017-08-01

The American military is embarking on the 'Third Offset'-a strategy designed to produce seismic shifts in the future of warfare. Central to the approach is the conjoining of humans, technology, and machines to deliver a decisive advantage on the battlefield. Because technology will spread rapidly and globally, tactical overmatch will occur when American operators possess a competitive edge in cognition. Investigation of cognitive enhancing therapeutics is not widely articulated as an adjunct to the Third Offset, yet failure to study promising agents could represent a strategic vulnerability. Because of its legacy of research into therapeutic agents to enhance human-machine interplay, the aerospace medical community represents a front-running candidate to perform this work. Notably, there are strong signals emanating from gambling, academic, and video-gaming enterprises that already-developed stimulants and other agents provide cognitive benefits. These agents should be studied not only for reasons of national security, but also because cognitive enhancement may be a necessary step in the evolution of humankind. To illustrate these points, this article will assert that: 1) the need to preserve and enhance physical and cognitive health will become more and more important over the next century; 2) aeromedical specialists are in a position to take the lead in the endeavor to enhance cognition; 3) signals of enhancement of the type useful to both military and medical efforts exist aplenty in today's society; and 4) the aeromedical community should approach human enhancement research deliberately but carefully.Malish RG. The importance of the study of cognitive performance enhancement for U.S. national security. Aerosp Med Hum Perform. 2017; 88(8):773-778.

The influence of learning methods on collaboration: prior repeated retrieval enhances retrieval organization, abolishes collaborative inhibition, and promotes post-collaborative memory.

PubMed

Congleton, Adam R; Rajaram, Suparna

2011-11-01

Research on collaborative memory has unveiled the counterintuitive yet robust phenomenon that collaboration impairs group recall. A candidate explanation for this collaborative inhibition effect is the disruption of people's idiosyncratic retrieval strategies during collaboration, and it is hypothesized that employing methods that improve one's organization protects against retrieval disruption. Here it is investigated how one's learning method during the study phase--defined as either repeatedly studying or repeatedly retrieving information--influences retrieval organization and what effects this has on collaborative recall and post-collaborative individual recall. Results show that repeated retrieval consistently eliminated collaborative inhibition. This enabled participants to gain the most from re-exposure to materials recalled by their partners that they themselves did not recall and led to improvements in their individual memory following collaboration. This repeated retrieval advantage stemmed from the preferential manner in which this learning method strengthened retrieval organization. Findings are also discussed that reveal a relationship between retrieval organization and the interaction observed between learning method and short versus long delay seen in the testing effect literature. Finally, results show that the elusive benefits of cross-cuing during collaboration may be best detected with a longer study-test delay. Together, these findings illuminate when and how collaboration can enhance memory.

KIC 8462852 Brightness Pattern Repeating Every 1600 days

NASA Astrophysics Data System (ADS)

Gary, Bruce; Bourne, Rafik

2017-12-01

Observations of KIC 8462852 (aka Boyajian's Star) reveal a yearlong fade pattern that is remarkably similar to the fade pattern derived from Kepler mission observations. The ground-based observations reported here can be described as a gradual fade that ended in late 2016 with the beginning of a yearlong U-shaped fade of 1.1 percent. Near the end of this U-shaped fade a series of very brief dips occurred. The Kepler data exhibit a similar pattern 1600 days earlier, except with an abrupt end of observations before the U-shape recovery. Observations lasting many years are needed, especially during our predicted repeat of the U-shape and short dip pattern in 2021.

7 CFR 51.3053 - U.S. No. 3.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946... Standards for Florida Avocados Grades § 51.3053 U.S. No. 3. “U.S. No. 3” consists of avocados of similar...

Predissociation of oxygen in the B3Sigma(u)(-) state

NASA Technical Reports Server (NTRS)

Chiu, S. S.-L.; Cheung, A. S.-C.; Finch, M.; Jamieson, M. J.; Yoshino, K.; Dalgarno, A.; Parkinson, W. H.

1992-01-01

The predissociation linewidths and level shifts of vibrational levels of three oxygen isotopic molecules (O2)-16, (O-16)(O-18), and (O2)-18 arising from the interactions of the B3Sigma(u)(-) state with the four repulsive states 5Pi(u), 3Sigma(u)(+), 3Pi(u), and 1Pi(u) have been calculated. A set of parameters characterizing these interactions has been determined. Good agreement between calculated and experimental predissociation widths and shifts has been obtained for all the three isotopic molecules.

Intergenic Variable-Number Tandem-Repeat Polymorphism Upstream of rocA Alters Toxin Production and Enhances Virulence in Streptococcus pyogenes.

PubMed

Zhu, Luchang; Olsen, Randall J; Horstmann, Nicola; Shelburne, Samuel A; Fan, Jia; Hu, Ye; Musser, James M

2016-07-01

Variable-number tandem-repeat (VNTR) polymorphisms are ubiquitous in bacteria. However, only a small fraction of them has been functionally studied. Here, we report an intergenic VNTR polymorphism that confers an altered level of toxin production and increased virulence in Streptococcus pyogenes The nature of the polymorphism is a one-unit deletion in a three-tandem-repeat locus upstream of the rocA gene encoding a sensor kinase. S. pyogenes strains with this type of polymorphism cause human infection and produce significantly larger amounts of the secreted cytotoxins S. pyogenes NADase (SPN) and streptolysin O (SLO). Using isogenic mutant strains, we demonstrate that deleting one or more units of the tandem repeats abolished RocA production, reduced CovR phosphorylation, derepressed multiple CovR-regulated virulence factors (such as SPN and SLO), and increased virulence in a mouse model of necrotizing fasciitis. The phenotypic effect of the VNTR polymorphism was nearly the same as that of inactivating the rocA gene. In summary, we identified and characterized an intergenic VNTR polymorphism in S. pyogenes that affects toxin production and virulence. These new findings enhance understanding of rocA biology and the function of VNTR polymorphisms in S. pyogenes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Combination of doxorubicin and low-intensity ultrasound causes a synergistic enhancement in cell killing and an additive enhancement in apoptosis induction in human lymphoma U937 cells.

PubMed

Yoshida, Toru; Kondo, Takashi; Ogawa, Ryohei; Feril, Loreto B; Zhao, Qing-Li; Watanabe, Akihiko; Tsukada, Kazuhiro

2008-04-01

Potential clinical use of ultrasound (US) in enhancing the effects of anticancer drugs in the treatment of cancers has been highlighted in previous reports. Increased uptake of drugs by the cancer cells due to US has been suggested as a mechanism. However, the precise mechanism of the enhancement has not yet been elucidated. Here, the combined effects of low-intensity pulsed US and doxorubicin (DOX) on cell killing and apoptosis induction of U937 cells, and mechanisms involved were investigated. Human myelomonocytic lymphoma U937 cells were used for the experiments. Experiments were conducted in 4 groups: (1) non-treated, (2) DOX treated (DOX), (3) US treated (US), and (4) combined (DOX + US). In DOX +US, cells were exposed to 5 microM DOX for 30 min and sonicated by 1 MHz pulsed US (PRF 100 Hz, DF 10%) at intensities of 0.2-0.5 W/cm(2) for 60 s. The cells were washed and incubated for 6 h. The viability was evaluated by Trypan blue dye exclusion test and apoptosis and incorporation of DOX was assessed by flow cytometry. Involvement of sonoporation in molecular incorporation was evaluated using FITC-dextran, hydroxyl radical formation was measured by electron paramagnetic resonance-spin trapping, membrane alteration including lipid peroxidation and membrane fluidity by DOX was evaluated using cis-parinaric acid and perylene fluorescence polarization method, respectively. Synergistic enhancement in cell killing and additive enhancement in induction of apoptosis were observed at and above 0.3 W/cm(2). No enhancement was observed at 0.2 W/cm(2) in cell killing and induction of apoptosis. Hydroxyl radicals formation was detected at and above 0.3 W/cm(2). The radicals were produced more in the DOX + US than US alone. Incorporation of DOX was increased 13% in DOX + US (vs. DOX) at 0.5 W/cm(2). Involvement of sonoporation for increase of drug uptake was suggested by experiment using FITC-labeled dextran. We made the hypothesis that DOX treatment made the cells weaken

Enhancement of NH3 Gas Sensitivity at Room Temperature by Carbon Nanotube-Based Sensor Coated with Co Nanoparticles

PubMed Central

Nguyen, Lich Quang; Phan, Pho Quoc; Duong, Huyen Ngoc; Nguyen, Chien Duc; Nguyen, Lam Huu

2013-01-01

Multi-walled carbon nanotube (MWCNT) film has been fabricated onto Pt-patterned alumina substrates using the chemical vapor deposition method for NH3 gas sensing applications. The MWCNT-based sensor is sensitive to NH3 gas at room temperature. Nanoclusters of Co catalysts have been sputtered on the surface of the MWCNT film to enhance gas sensitivity with respect to unfunctionalized CNT films. The gas sensitivity of Co-functionalized MWCNT-based gas sensors is thus significantly improved. The sensor exhibits good repeatability and high selectivity towards NH3, compared with alcohol and LPG. PMID:23364198

Enhancement of NH3 gas sensitivity at room temperature by carbon nanotube-based sensor coated with Co nanoparticles.

PubMed

Nguyen, Lich Quang; Phan, Pho Quoc; Duong, Huyen Ngoc; Nguyen, Chien Duc; Nguyen, Lam Huu

2013-01-30

Multi-walled carbon nanotube (MWCNT) film has been fabricated onto Pt-patterned alumina substrates using the chemical vapor deposition method for NH(3) gas sensing applications. The MWCNT-based sensor is sensitive to NH(3) gas at room temperature. Nanoclusters of Co catalysts have been sputtered on the surface of the MWCNT film to enhance gas sensitivity with respect to unfunctionalized CNT films. The gas sensitivity of Co-functionalized MWCNT-based gas sensors is thus significantly improved. The sensor exhibits good repeatability and high selectivity towards NH(3), compared with alcohol and LPG.

Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation

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

Mathew, Sherin T.; Bergström, Petra; Hammarsten, Ola, E-mail: ola.hammarsten@clinchem.gu.se

2014-05-01

Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA andmore » reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2′-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage. - Highlights: • Repeated treatment with sulforaphane protects fibroblasts from ionizing radiation • Repeated sulforaphane treatment attenuates radiation induced ROS and DNA damage • Sulforaphane mediated protection is Nrf2 dependent.« less

Repeated isoflurane exposure and neuroapoptosis in the midgestation fetal sheep brain.

PubMed

Olutoye, Olutoyin A; Sheikh, Fariha; Zamora, Irving J; Yu, Ling; Akinkuotu, Adesola C; Adesina, Adekunle M; Olutoye, Oluyinka O

2016-04-01

Advances in surgery and technology have resulted in increased in-utero procedures. However, the effect of anesthesia on the fetal brain is not fully known. The inhalational anesthetic agent, isoflurane, other gamma amino butyric acid agonists (benzodiazepines, barbiturates, propofol, other inhalation anesthetics), and N-methyl D aspartate antagonists, eg, ketamine, have been shown to induce neuroapoptosis. The ovine model has been used extensively to study maternal-fetal physiologic interactions and to investigate different surgical interventions on the fetus. The purpose of this study was to determine effects of different doses and duration of isoflurane on neuroapoptosis in midgestation fetal sheep. We hypothesized that repeated anesthetic exposure and high concentrations of isoflurane would result in increased neuroapoptosis. Time-dated, pregnant sheep at 70 days gestation (term 145 days) received either isoflurane 2% × 1 hour, 4% × 3 hours, or 2% × 1 hour every other day for 3 exposures (repeated exposure group). Euthanasia occurred following anesthetic exposure and fetal brains were processed. Neuroapoptosis was detected by immunohistochemistry using anticaspase-3 antibodies. Fetuses unexposed to anesthesia served as controls. Another midgestation group with repeated 2% isoflurane exposure was examined at day 130 (long-term group) and neuronal cell density compared to age-matched controls. Representative sections of the brain were analyzed using Aperio Digital imaging (Leica Microsystems Inc, Buffalo Grove, IL). Data, reported by number of neurons per cubic millimeter of brain tissue are presented as means and SEM. Data were analyzed using the Mann-Whitney U and Kruskal-Wallis tests as appropriate. A total of 34 fetuses were studied. There was no significant difference in neuroapoptosis observed in fetuses exposed to 2% isoflurane for 1 hour or 4% isoflurane for 3 hours. Increased neuroapoptosis was observed in the frontal cortex following repeated 2

Uranium isotope fractionation induced by aqueous speciation: Implications for U isotopes in marine CaCO3 as a paleoredox proxy

NASA Astrophysics Data System (ADS)

Chen, Xinming; Romaniello, Stephen J.; Anbar, Ariel D.

2017-10-01

Natural variations of 238U/235U in marine CaCO3 rocks are being explored as a novel paleoredox proxy to investigate oceanic anoxia events. Although it is generally assumed that U isotopes in CaCO3 directly record 238U/235U of seawater, recently published laboratory experiments demonstrate slight U isotope fractionation during U(VI) incorporation into abiotic calcium carbonates. This fractionation is hypothesized to depend on aqueous U(VI) speciation, which is controlled by pH, ionic strength, pCO2 and Mg2+ and Ca2+ concentrations. Secular variation in seawater chemistry could lead to changes in aqueous U(VI) speciation, and thus, may affect the extent of U isotope fractionation during U(VI) incorporation into CaCO3. In this study, we combine estimates of seawater composition over the Phanerozoic with a model of aqueous U speciation and isotope fractionation to explore variations in the expected offset between the U isotope composition of seawater and primary marine CaCO3 through time. We find that U isotope fractionation between U in primary marine CaCO3 and seawater could have varied between 0.11 and 0.23‰ over the Phanerozoic due to secular variations in seawater chemistry. Such variations would significantly impact estimates of the extent of marine anoxia derived from the U isotope record. For example, at the Permo-Triassic boundary, this effect might imply that the estimated extent of anoxia is ∼32% more extreme than previously inferred. One significant limitation of our model is that the existing experimental database covers only abiotic carbonate precipitation, and does not include a possible range of biological effects which might enhance or suppress the range of isotopic fractionation calculated here. As biotic carbonates dominate the marine carbonate record, more work is need to assess controls on U isotopic fractionation into biotic marine carbonates.

Preparation of U.sub.3 O.sub.8

DOEpatents

Johnson, David R.

1980-01-01

A method is described for the preparation of U.sub.3 O.sub.8 nuclear fuel material by direct precipitation of uranyl formate monohydrate from uranyl nitrate solution. The uranyl formate monohydrate precipitate is removed, dried and calcined to produce U.sub.3 O.sub.8 having a controlled particle size distribution.

Chronic exercise prevents repeated restraint stress-provoked enhancement of immobility in forced swimming test in ovariectomized mice.

PubMed

Han, Tae-Kyung; Lee, Jang-Kyu; Leem, Yea-Hyun

2015-06-01

We assessed whether chronic treadmill exercise attenuated the depressive phenotype induced by restraint stress in ovariectomized mice (OVX). Immobility of OVX in the forced swimming test was comparable to that of sham mice (CON) regardless of the postoperative time. Immobility was also no difference between restrained mice (exposure to periodic restraint for 21 days; RST) and control mice (CON) on post-exposure 2nd and 9th day, but not 15th day. In contrast, the immobility of ovariectomized mice with repeated stress (OVX + RST) was profoundly enhanced compared to ovariectomized mice-alone (OVX), and this effect was reversed by chronic exercise (19 m/min, 60 min/day, 5 days/week for 8 weeks; OVX + RST + Ex) or fluoxetine administration (20 mg/kg, OVX + RST + Flu). In parallel with behavioral data, the immunoreactivity of Ki-67 and doublecortin (DCX) in OVX was significantly decreased by repeated stress. However, the reduced numbers of Ki-67- and DCX-positive cells in OVX + RST were restored in response to chronic exercise (OVX + RST + Ex) and fluoxetine (OVX + RST + Flu). In addition, the expression pattern of cAMP response element-binding protein (CREB) and calcium-calmodulin-dependent kinase IV (CaMKIV) was similar to that of the hippocampal proliferation and neurogenesis markers (Ki-67 and DCX, respectively). These results suggest that menopausal depression may be induced by an interaction between repeated stress and low hormone levels, rather than a deficit in ovarian secretion alone, which can be improved by chronic exercise.

Virtual surgical planning and 3D printing in repeat calvarial vault reconstruction for craniosynostosis: technical note.

PubMed

LoPresti, Melissa; Daniels, Bradley; Buchanan, Edward P; Monson, Laura; Lam, Sandi

2017-04-01

Repeat surgery for restenosis after initial nonsyndromic craniosynostosis intervention is sometimes needed. Calvarial vault reconstruction through a healed surgical bed adds a level of intraoperative complexity and may benefit from preoperative and intraoperative definitions of biometric and aesthetic norms. Computer-assisted design and manufacturing using 3D imaging allows the precise formulation of operative plans in anticipation of surgical intervention. 3D printing turns virtual plans into anatomical replicas, templates, or customized implants by using a variety of materials. The authors present a technical note illustrating the use of this technology: a repeat calvarial vault reconstruction that was planned and executed using computer-assisted design and 3D printed intraoperative guides.

Gadolinium Enhanced MR Coronary Vessel Wall Imaging at 3.0 Tesla.

PubMed

Kelle, Sebastian; Schlendorf, Kelly; Hirsch, Glenn A; Gerstenblith, Gary; Fleck, Eckart; Weiss, Robert G; Stuber, Matthias

2010-10-11

Purpose. We evaluated the influence of the time between low-dose gadolinium (Gd) contrast administration and coronary vessel wall enhancement (LGE) detected by 3T magnetic resonance imaging (MRI) in healthy subjects and patients with coronary artery disease (CAD). Materials and Methods. Four healthy subjects (4 men, mean age 29 ± 3 years and eleven CAD patients (6 women, mean age 61 ± 10 years) were studied on a commercial 3.0 Tesla (T) whole-body MR imaging system (Achieva 3.0 T; Philips, Best, The Netherlands). T1-weighted inversion-recovery coronary magnetic resonance imaging (MRI) was repeated up to 75 minutes after administration of low-dose Gadolinium (Gd) (0.1 mmol/kg Gd-DTPA). Results. LGE was seen in none of the healthy subjects, however in all of the CAD patients. In CAD patients, fifty-six of 62 (90.3%) segments showed LGE of the coronary artery vessel wall at time-interval 1 after contrast. At time-interval 2, 34 of 42 (81.0%) and at time-interval 3, 29 of 39 evaluable segments (74.4%) were enhanced. Conclusion. In this work, we demonstrate LGE of the coronary artery vessel wall using 3.0 T MRI after a single, low-dose Gd contrast injection in CAD patients but not in healthy subjects. In the majority of the evaluated coronary segments in CAD patients, LGE of the coronary vessel wall was already detectable 30-45 minutes after administration of the contrast agent.

Functional centromeres in Astragalus sinicus include a compact centromere-specific histone H3 and a 20-bp tandem repeat.

PubMed

Tek, Ahmet L; Kashihara, Kazunari; Murata, Minoru; Nagaki, Kiyotaka

2011-11-01

The centromere plays an essential role for proper chromosome segregation during cell division and usually harbors long arrays of tandem repeated satellite DNA sequences. Although this function is conserved among eukaryotes, the sequences of centromeric DNA repeats are variable. Most of our understanding of functional centromeres, which are defined by localization of a centromere-specific histone H3 (CENH3) protein, comes from model organisms. The components of the functional centromere in legumes are poorly known. The genus Astragalus is a member of the legumes and bears the largest numbers of species among angiosperms. Therefore, we studied the components of centromeres in Astragalus sinicus. We identified the CenH3 homolog of A. sinicus, AsCenH3 that is the most compact in size among higher eukaryotes. A CENH3-based assay revealed the functional centromeric DNA sequences from A. sinicus, called CentAs. The CentAs repeat is localized in A. sinicus centromeres, and comprises an AT-rich tandem repeat with a monomer size of 20 nucleotides.

Accumulate-Repeat-Accumulate-Accumulate Codes

NASA Technical Reports Server (NTRS)

Divsalar, Dariush; Dolinar, Samuel; Thorpe, Jeremy

2007-01-01

Accumulate-repeat-accumulate-accumulate (ARAA) codes have been proposed, inspired by the recently proposed accumulate-repeat-accumulate (ARA) codes. These are error-correcting codes suitable for use in a variety of wireless data-communication systems that include noisy channels. ARAA codes can be regarded as serial turbolike codes or as a subclass of low-density parity-check (LDPC) codes, and, like ARA codes they have projected graph or protograph representations; these characteristics make it possible to design high-speed iterative decoders that utilize belief-propagation algorithms. The objective in proposing ARAA codes as a subclass of ARA codes was to enhance the error-floor performance of ARA codes while maintaining simple encoding structures and low maximum variable node degree.

Heavy-ion irradiation effects on U3O8 incorporated Gd2Zr2O7 waste forms.

PubMed

Lu, Xirui; Shu, Xiaoyan; Chen, Shunzhang; Zhang, Kuibao; Chi, Fangtin; Zhang, Haibin; Shao, Dadong; Mao, Xueli

2018-06-12

In this research, the heavy-ion irradiation effects of U-bearing Gd 2 Zr 2 O 7 ceramics were explored for nuclear waste immobilization. U 3 O 8 was designed to be incorporated into Gd 2 Zr 2 O 7 from two different routes in the form of (Gd 1-4 x U 2 x ) 2 (Zr 1- x U x ) 2 O 7 (x = 0.1, 0.14). The self-irradiation of actinide nuclides was simulated by Xe 20+ heavy-ion radiation under different fluences. Grazing incidence X-ray diffraction (GIXRD) analysis reveals the relationship between radiation dose, damage and depth. The radiation tolerance is promoted with the increment of U 3 O 8 content in the discussed range. Raman spectroscopy testifies the enhancement of radiation tolerance and microscopically existed phase evolution from the chemical bond vibrations. In addition, the microstructure and elemental distribution of the irradiated samples were analyzed as well. The amorphization degree of the sample surface declines as the U content was elevated from x = 0.1 to x = 0.14. Copyright © 2018 Elsevier B.V. All rights reserved.

Inhibition of STAT3 and ErbB2 Suppresses Tumor Growth, Enhances Radiosensitivity, and Induces Mitochondria-Dependent Apoptosis in Glioma Cells

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

Gao Ling; Li Fengsheng; Dong Bo

2010-07-15

Purpose: Constitutively activated signal transducer and activator of transcription 3 (STAT3) and ErbB2 are involved in the pathogenesis of many tumors, including astrocytoma. Inactivation of these molecules is reported to result in radiosensitization. The purpose of this study was to investigate whether inhibition of STAT3, ErbB2, or both could enhance radiotherapy in the human glioma model (U251 and U87 cell lines). Methods and Materials: The RNAi plasmids targeting STAT3 or ErbB2 were constructed, and their downregulatory effects on target proteins were examined by immunoblotting. After combination treatment of RNAi with or without irradiation, the cell viability was determined using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazoliummore » bromide (MTT) and clonogenic assays. The in vivo effect of combined treatment was determined using the U251 xenograft model. The apoptosis caused by the inhibition of STAT3 and ErbB2 was detected, and the mechanism involved in the apoptosis was investigated, including increases in caspase proteins, mitochondrial damage, and the expression of key modulating protein of different apoptosis pathways. Results: Transfection of U251 cells with STAT3 or ErbB2 siRNA plasmids specifically reduced their target gene expressions. Inhibition of STAT3 or ErbB2 greatly decreased glioma cell survival after 2, 4, or 6 Gy irradiation. Inhibition of STAT3 and ErbB2 also enhanced radiation-induced tumor growth inhibition in the U251 xenograft model. Furthermore, the suppression of either STAT3 or ErbB2 could induce U251 cell apoptosis, which was related primarily to the mitochondrial apoptotic pathway. Conclusions: These results indicated that simultaneous inhibition of STAT3 and ErbB2 expression can promote potent antitumor activity and radiosensitizing activity in human glioma.« less

Msh2-Msh3 Interferes with Okazaki Fragment Processing to Promote Trinucleotide Repeat Expansions

PubMed Central

Kantartzis, Athena; Williams, Gregory M.; Balakrishnan, Lata; Roberts, Rick L.; Surtees, Jennifer A.; Bambara, Robert A.

2012-01-01

Summary Trinucleotide repeat (TNR) expansions are the underlying cause of more than forty neurodegenerative and neuromuscular diseases, including myotonic dystrophy and Huntington’s disease. Although genetic evidence has attributed the cause of these diseases to errors in DNA replication and/or repair, clear molecular mechanisms have not been described. We have focused on the role of the mismatch repair complex Msh2-Msh3 in promoting TNR expansions. We demonstrate that Msh2-Msh3 promotes CTG and CAG repeat expansions in vivo in Saccharomyces cerevisiae. We further provide biochemical evidence that Msh2-Msh3 directly interferes with normal Okazaki fragment processing by flap endonuclease1 (Rad27) and DNA Ligase I (Cdc9) in the presence of TNR sequences, thereby producing small, incremental expansion events. We believe that this is the first mechanistic evidence showing the interplay of replication and repair proteins in the expansion of sequences during lagging strand DNA replication. PMID:22938864

Msh2-Msh3 interferes with Okazaki fragment processing to promote trinucleotide repeat expansions.

PubMed

Kantartzis, Athena; Williams, Gregory M; Balakrishnan, Lata; Roberts, Rick L; Surtees, Jennifer A; Bambara, Robert A

2012-08-30

Trinucleotide repeat (TNR) expansions are the underlying cause of more than 40 neurodegenerative and neuromuscular diseases, including myotonic dystrophy and Huntington's disease. Although genetic evidence points to errors in DNA replication and/or repair as the cause of these diseases, clear molecular mechanisms have not been described. Here, we focused on the role of the mismatch repair complex Msh2-Msh3 in promoting TNR expansions. We demonstrate that Msh2-Msh3 promotes CTG and CAG repeat expansions in vivo in Saccharomyces cerevisiae. Furthermore, we provide biochemical evidence that Msh2-Msh3 directly interferes with normal Okazaki fragment processing by flap endonuclease1 (Rad27) and DNA ligase I (Cdc9) in the presence of TNR sequences, thereby producing small, incremental expansion events. We believe that this is the first mechanistic evidence showing the interplay of replication and repair proteins in the expansion of sequences during lagging-strand DNA replication. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

Repeated swim impairs serotonin clearance via a corticosterone-sensitive mechanism: organic cation transporter 3, the smoking gun.

PubMed

Baganz, Nicole; Horton, Rebecca; Martin, Kathryn; Holmes, Andrew; Daws, Lynette C

2010-11-10

Activation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with increased extracellular serotonin (5-HT) in limbic brain regions. The mechanism through which this occurs remains unclear. One way could be via HPA axis-dependent impairment of serotonin transporter (SERT) function, the high-affinity uptake mechanism for 5-HT. Consistent with this idea, we found that 5-HT clearance rate in hippocampus was dramatically reduced in mice exposed to repeated swim, a stimulus known to activate the HPA axis. However, this phenomenon also occurred in mice lacking SERT, ruling out SERT as a mechanism. The organic cation transporter 3 (OCT3) is emerging as an important regulator of brain 5-HT. Moreover, corticosterone, which is released upon HPA axis activation, blocks 5-HT uptake by OCT3. Repeated swim produced a persistent elevation in plasma corticosterone, and, consistent with prolonged blockade by corticosterone, we found that OCT3 expression and function were reduced in these mice. Importantly, this effect of repeated swim to reduce 5-HT clearance rate was corticosterone dependent, as evidenced by its absence in adrenalectomized mice, in which plasma corticosterone levels were essentially undetectable. Behaviorally, mice subjected to repeated swim spent less time immobile in the tail suspension test than control mice, but responded similarly to SERT- and norepinephrine transporter-selective antidepressants. Together, these results show that reduced 5-HT clearance following HPA axis activation is likely mediated, at least in part, by the corticosterone-sensitive OCT3, and that drugs developed to selectively target OCT3 (unlike corticosterone) may be candidates for the development of novel antidepressant medications.

IGF1 (CA)19 repeat and IGFBP3 -202 A/C genotypes and the risk of prostate cancer in Black and White men.

PubMed

Schildkraut, Joellen M; Demark-Wahnefried, Wendy; Wenham, Robert M; Grubber, Janet; Jeffreys, Amy S; Grambow, Steven C; Marks, Jeffrey R; Moorman, Patricia G; Hoyo, Cathrine; Ali, Shazia; Walther, Philip J

2005-02-01

We investigated the relationship between the insulin-like growth factor-1 (IGF1) cytosine-adenine repeat (CA)(19) polymorphism located upstream of the gene's transcription start site, the insulin-like growth factor binding protein-3 (IGFBP3) -202 A/C promoter region polymorphism, and prostate cancer risk in Black and White men. Study subjects were U.S. veterans ages 41 to 75 years identified at the Durham Veterans Administration Medical Center over a 2.5-year period. Controls (n = 93) were frequency matched to cases (n = 100) based on race (Black or White) and age. Multivariable unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the associations between the polymorphisms and prostate cancer risk. For Blacks and Whites combined, an inverse association between prostate cancer and being homozygous for the most common IGF1 repeat allele, (CA)(19), (adjusted OR, 0.3; 95% CI, 0.1-0.7) was observed. Similar associations were noted for both Blacks (OR, 0.2; 95% CI, 0.0-0.8) and Whites (OR, 0.4; 95% CI, 0.1-1.6) separately. No statistically significant associations between the IGFBP3 C allele and prostate cancer were noted for Blacks (adjusted OR, 2.3; 95% CI, 0.8-6.2) or Whites (OR, 1.0; 95% CI, 0.3-3.1). The prevalence of the homozygous IGF1 (CA)(19) genotype was much lower in Black controls (21%) than White controls (46%), which may, in part, explain the increased prostate cancer incidence in Black versus White men. Further research is needed to confirm these findings.

Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation.

PubMed

Mathew, Sherin T; Bergström, Petra; Hammarsten, Ola

2014-05-01

Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA and reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2'-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage. Copyright © 2014 Elsevier Inc. All rights reserved.

Production of laccase by Coriolus versicolor and its application in decolorization of dyestuffs: (I). Production of laccase by batch and repeated-batch processes.

PubMed

Lin, Jian-Ping; Wei, Lian; Xia, Li-Ming; Cen, Pei-Lin

2003-01-01

The production of laccase by Coriolus versicolor was studied. The effect of cultivation conditions on laccase production by Coriolus versicolor was examined to obtain optimal medium and cultivation conditions. Both batch and repeated-batch processes were performed for laccase production. In repeated-batch fermentation with self-immobilized mycelia, total of 14 cycles were performed with laccase activity in the range between 3.4 and 14.8 U/ml.

Coactivator-associated arginine methyltransferase 1 enhances transcriptional activity of the human T-cell lymphotropic virus type 1 long terminal repeat through direct interaction with Tax.

PubMed

Jeong, Soo-Jin; Lu, Hanxin; Cho, Won-Kyung; Park, Hyeon Ung; Pise-Masison, Cynthia; Brady, John N

2006-10-01

In this study, we demonstrate that the coactivator-associated arginine methyltransferase 1 (CARM1), which methylates histone H3 and other proteins such as p300/CBP, is positively involved in the regulation of Tax transactivation. First, transfection studies demonstrated that overexpression of CARM1 wild-type protein resulted in increased Tax transactivation of the human T-cell lymphotropic virus type 1 (HTLV-1) long terminal repeat (LTR). In contrast, transfection of a catalytically inactive CARM1 methyltransferase mutant did not enhance Tax transactivation. CARM1 facilitated Tax transactivation of the CREB-dependent cellular GEM promoter. A direct physical interaction between HTLV-1 Tax and CARM1 was demonstrated using in vitro glutathione S-transferase-Tax binding assays, in vivo coimmunoprecipitation, and confocal microscopy experiments. Finally, chromatin immunoprecipitation analysis of the activated HTLV-1 LTR promoter showed the association of CARM1 and methylated histone H3 with the template DNA. In vitro, Tax facilitates the binding of CARM1 to the transcription complex. Together, our data provide evidence that CARM1 enhances Tax transactivation of the HTLV-1 LTR through a direct interaction between CARM1 and Tax and this binding promotes methylation of histone H3 (R2, R17, and R26).

Laxative effect of repeated Daiokanzoto is attributable to decrease in aquaporin-3 expression in the colon.

PubMed

Kon, Risako; Yamamura, Miho; Matsunaga, Yukari; Kimura, Hiroshi; Minami, Moe; Kato, Saki; Ikarashi, Nobutomo; Sugiyama, Kiyoshi

2018-03-01

Daiokanzoto (DKT) exerts its laxative effect via colonic inflammation caused by sennoside A in Daio (rhubarb). Previously, we showed that the laxative effect of sennoside A is related to decreased aquaporin-3 (AQP3) expression in mucosal epithelial cells due to colonic inflammation. We also found that a combination of glycyrrhizin, an ingredient in Kanzo (glycyrrhiza), and sennoside A attenuates the inflammatory response induced by sennoside A and reduces its laxative effect. These findings indicate that DKT may be a long-term treatment for chronic constipation, but there is no evidence supporting this hypothesis. In this study, we analyzed the laxative effect of repeated DKT administration, focusing on AQP3 expression in the colon. After rats were treated for 7 days, decreased AQP3 expression and the onset of diarrhea were observed in the DKT group, but were not seen in the Daio group either. Although the relative abundance of gut microbiota after repeated DKT administration was similar to that after control treatment, Daio reduced Lactobacillaceae, Bifidobacteriaceae, and Bacteroidaceae levels and markedly increased Lachnospiraceae levels. In this study, we show that DKT has a sustained laxative effect, even upon repeated use, probably because it maintains decreased AQP3 expression and gut microbiota homeostasis. This outcome therefore indicates that DKT can be used as a long-term treatment for chronic constipation.

Enhanced photo-stability and photocatalytic activity of Ag3PO4 via modification with BiPO4 and polypyrrole

NASA Astrophysics Data System (ADS)

Cai, Li; Jiang, Hui; Wang, Luxi

2017-10-01

Ag3PO4 photocatalysts modified with BiPO4 and polypyrrole (PPy) were successfully synthesized via a combination of co-precipitation hydrothermal technique and oxidative polymerization method. Their morphologies, structures and optical and electronic properties were characterized by means of scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscope (TEM), Brunauer-Emmett-Teller (BET) surface areas, X-ray diffraction (XRD), fourier transform infrared spectra (FT-IR), X-ray photo-electron spectroscopy (XPS), UV-vis diffuse reflection spectra (UV-vis DRS), photocurrent technique and electrochemical impedance spectra (EIS). The typical triphenylmethane dye (malachite green) was chosen as a target organic contaminants to estimate the photocatalytic activities and photo-stabilities of Ag3PO4-BiPO4-PPy heterostructures under visible light irradiation. The results indicated that the existence of BiPO4 and PPy not only showed great influences on the photocatalytic activity, but also significantly enhanced photo-stability of Ag3PO4 in repeated and long-term applications. The degradation conversion of Ag3PO4-BiPO4-PPy heterostructures (ABP-3) was 1.58 times of that of pure Ag3PO4. The photo-corrosion phenomenon of Ag3PO4 was effectively avoided. The photocatalytic activity of up to 87% in the Ag3PO4-BiPO4-PPy heterostructures (ABP-3) can be remained after five repeated cycles, while only about 33% of the degradation efficiency can be reserved in pure Ag3PO4. The possible mechanism of enhanced photo-stability and photocatalytic activity of Ag3PO4-BiPO4-PPy heterostructures was also discussed in this work.

Autoregulation of the Bacillus subtilis response regulator gene degU is coupled with the proteolysis of DegU-P by ClpCP.

PubMed

Ogura, Mitsuo; Tsukahara, Kensuke

2010-03-01

The response regulator DegU and its cognate kinase DegS constitute a two-component system in Bacillus subtilis that regulates many cellular processes, including exoprotease production and competence development. Using DNA footprint assay, gel shift assay and mutational analyses of P3degU-lacZ fusions, we showed that phosphorylated DegU (DegU-P) binds to two direct repeats (DR1 and DR2) of the consensus DegU-binding sequence in the P3degU promoter. The alteration of chromosomal DR2 severely decreased degU expression, demonstrating its importance in positive autoregulation of degU. Observation of DegU protein levels suggested that DegU is degraded. Western blot analysis of DegU in disruption mutants of genes encoding various ATP-dependent proteases strongly suggested that ClpCP degrades DegU. Moreover, when de novo protein synthesis was blocked, DegU was rapidly degraded in the wild-type but not in the clpC and clpP strains, and DegU with a mutated phosphorylation site was much stable. These results suggested preferential degradation of DegU-P by ClpCP, but not of unphosphorylated DegU. We confirmed that DegU-P was degraded preferentially using an in vitro ClpCP degradation system. Furthermore, a mutational analysis showed that the N-terminal region of DegU is important for proteolysis.

(234)U/(238)U signatures associated with uranium ore bodies: part 1 Ranger 3.

PubMed

Lowson, Richard T; McIntyre, Mark G

2013-04-01

The Ranger 3 ore body is an early Proterozoic U ore body in the Alligator Rivers U province, Northern Territory, Australia. It has surface expression with a redox front located between 30 and 50 m below the surface. The ground water U concentration and (234)U/(238)U AR signature in the top 10 m of the weathered zone are reported for 357 samples collected over 4 wet seasons, at 5 depths, along a transect in-line with the hydraulic gradient and along the centre line of the ore body and its associated dispersion halo. The results show that the weathered zone displays a general U isotope feature for this type of ore body with the (234)U/(238)U AR for the ground water and amorphous phase of the solid matrix being less than 1. The ground water (234)U/(238)U AR is independent of the annual monsoonal climate and depth within the range surface to 10 m. In the vicinity of the U ore body the ground water (234)U/(238)U AR is 0.75 and is very similar to the (234)U/(238)U AR of the amorphous phase of the solid (0.76). The (234)U/(238)U ARs of the amorphous phase and ground water rise and separate to values of 0.88 and 1.02 at the end of the transect. The rise and separation in (234)U/(238)U AR are interpreted as evidence that the source of the U in the ground water is from the water-soluble sub-phase of the amorphous phase and that the ground water flow is too fast to allow the processes occurring across the solid-water interface to reach chemical equilibrium. The data set is a robust characterisation of the coarse and fine detail of the (234)U/(238)U AR signature in the weathered zone of U ore bodies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Self-association and domain rearrangements between complement C3 and C3u provide insight into the activation mechanism of C3.

PubMed

Li, Keying; Gor, Jayesh; Perkins, Stephen J

2010-10-01

Component C3 is the central protein of the complement system. During complement activation, the thioester group in C3 is slowly hydrolysed to form C3u, then the presence of C3u enables the rapid conversion of C3 into functionally active C3b. C3u shows functional similarities to C3b. To clarify this mechanism, the self-association properties and solution structures of C3 and C3u were determined using analytical ultracentrifugation and X-ray scattering. Sedimentation coefficients identified two different dimerization events in both proteins. A fast dimerization was observed in 50 mM NaCl but not in 137 mM NaCl. Low amounts of a slow dimerization was observed for C3u and C3 in both buffers. The X-ray radius of gyration RG values were unchanged for both C3 and C3u in 137 mM NaCl, but depend on concentration in 50 mM NaCl. The C3 crystal structure gave good X-ray fits for C3 in 137 mM NaCl. By randomization of the TED (thioester-containing domain)/CUB (for complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domains in the C3b crystal structure, X-ray fits showed that the TED/CUB domains in C3u are extended and differ from the more compact arrangement of C3b. This TED/CUB conformation is intermediate between those of C3 and C3b. The greater exposure of the TED domain in C3u (which possesses the hydrolysed reactive thioester) accounts for the greater self-association of C3u in low-salt conditions. This conformational variability of the TED/CUB domains would facilitate their interactions with a broad range of antigenic surfaces. The second dimerization of C3 and C3u may correspond to a dimer observed in one of the crystal structures of C3b.

Trends in Repeat Births and Use of Postpartum Contraception Among Teens - United States, 2004-2015.

PubMed

Dee, Deborah L; Pazol, Karen; Cox, Shanna; Smith, Ruben A; Bower, Katherine; Kapaya, Martha; Fasula, Amy; Harrison, Ayanna; Kroelinger, Charlan D; D'Angelo, Denise; Harrison, Leslie; Koumans, Emilia H; Mayes, Nikki; Barfield, Wanda D; Warner, Lee

2017-04-28

Teen* childbearing (one or more live births before age 20 years) can have negative health, social, and economic consequences for mothers and their children (1). Repeat teen births (two or more live births before age 20 years) can constrain the mother's ability to take advantage of educational and workforce opportunities (2), and are more likely to be preterm or of low birthweight than first teen births (3). Despite the historic decline in the U.S. teen birth rate during 1991-2015, from 61.8 to 22.3 births per 1,000 females aged 15-19 years (4), many teens continue to have repeat births (3). The American College of Obstetricians and Gynecologists and the American Academy of Pediatrics both recommend that clinicians counsel women (including teens) during prenatal care about birth spacing and postpartum contraceptive use (5), including the safety and effectiveness of long-acting reversible methods that can be initiated immediately postpartum. To expand upon prior research assessing patterns and trends in repeat childbearing and postpartum contraceptive use among teens with a recent live birth (i.e., 2-6 months after delivery) (3), CDC analyzed data from the National Vital Statistics System natality files (2004 and 2015) and the Pregnancy Risk Assessment Monitoring System (PRAMS; 2004-2013). The number and proportion of teen births that were repeat births decreased from 2004 (82,997; 20.1%) to 2015 (38,324; 16.7%); in 2015, the percentage of teen births that were repeat births varied by state from 10.6% to 21.4%. Among sexually active teens with a recent live birth, postpartum use of the most effective contraceptive methods (intrauterine devices and contraceptive implants) increased from 5.3% in 2004 to 25.3% in 2013; however, in 2013, approximately one in three reported using either a least effective method (15.7%) or no method (17.2%). Strategies that comprehensively address the social and health care needs of teen parents can facilitate access to and use of

Enhanced mutagenesis parallels enhanced reactivation of herpes virus in a human cell line.

PubMed Central

Lytle, C D; Knott, D C

1982-01-01

U.v. irradiation of human NB-E cells results in enhanced mutagenesis and enhanced reactivation of u.v.-irradiated H-1 virus grown in those cells ( Cornelis et al., 1982). This paper reports a similar study using herpes simplex virus (HSV) in NB-E cells. The mutation frequency of HSV (resistance of virus plaque formation to 40 micrograms/ml iododeoxycytidine ) increased approximately linearly with exposure of the virus to u.v. radiation. HSV grown in unirradiated cells gave a slope of 1.8 X 10(-5)m2/J, with 3.2 X 10(-5)m2/J for HSV grown in cells irradiated (3 J/m2) 24 h before infection. There was no evidence for mutagenesis of unirradiated virus by irradiated cells, as seen with H-1 virus. Enhanced reactivation of irradiated HSV in parallel cultures increased virus survival, manifested as a change in slope of the final component of the two-component survival curve from a D0 of 27 J/m2 in unirradiated cells to 45 J/m2 in irradiated cells. Thus, enhanced mutagenesis and enhanced reactivation occurred for irradiated HSV in NB-E cells. The difference in the enhanced mutagenesis of HSV (dependent on damaged DNA sites) and of H-1 virus (primarily independent of damaged DNA sites) is discussed in terms of differences in DNA polymerases. PMID:6329698

Marked Phenotypic Heterogeneity Associated with Expansion of a CAG Repeat Sequence at the Spinocerebellar Ataxia 3/Machado-Joseph Disease Locus

PubMed Central

Cancel, Géraldine; Abbas, Nacer; Stevanin, Giovanni; Dürr, Alexandra; Chneiweiss, Hervé; Néri, Christian; Duyckaerts, Charles; Penet, Christiane; Cann, Howard M.; Agid, Yves; Brice, Alexis

1995-01-01

The spinocerebellar ataxia 3 locus (SCA3) for type I autosomal dominant cerebellar ataxia (ADCA type I), a clinically and genetically heterogeneous group of neuro-degenerative disorders, has been mapped to chromosome 14q32.1. ADCA type I patients from families segregating SCA3 share clinical features in common with those with Machado-Joseph disease (MJD), the gene of which maps to the same region. We show here that the disease gene segregating in each of three French ADCA type I kindreds and in a French family with neuropatho-logical findings suggesting the ataxochoreic form of dentatorubropallidoluysian atrophy carries an expanded CAG repeat sequence located at the same locus as that for MJD. Analysis of the mutation in these families shows a strong negative correlation between size of the expanded CAG repeat and age at onset of clinical disease. Instability of the expanded triplet repeat was not found to be affected by sex of the parent transmitting the mutation. Evidence was found for somatic and gonadal mosaicism for alleles carrying expanded trinucleotide repeats. ImagesFigure 3Figure 5 PMID:7573040

Evolution of metastable state molecules N2(A3 Σu+) in a nanosecond pulsed discharge: A particle-in-cell/Monte Carlo collisions simulation

NASA Astrophysics Data System (ADS)

Gao, Liang; Sun, Jizhong; Feng, Chunlei; Bai, Jing; Ding, Hongbin

2012-01-01

A particle-in-cell plus Monte Carlo collisions method has been employed to investigate the nitrogen discharge driven by a nanosecond pulse power source. To assess whether the production of the metastable state N2(A3 Σu+) can be efficiently enhanced in a nanosecond pulsed discharge, the evolutions of metastable state N2(A3 Σu+) density and electron energy distribution function have been examined in detail. The simulation results indicate that the ultra short pulse can modulate the electron energy effectively: during the early pulse-on time, high energy electrons give rise to quick electron avalanche and rapid growth of the metastable state N2(A3 Σu+) density. It is estimated that for a single pulse with amplitude of -9 kV and pulse width 30 ns, the metastable state N2(A3 Σu+) density can achieve a value in the order of 109 cm-3. The N2(A3 Σu+) density at such a value could be easily detected by laser-based experimental methods.

Variable flip angle 3D ultrashort echo time (UTE) T1 mapping of mouse lung: A repeatability assessment.

PubMed

Alamidi, Daniel F; Smailagic, Amir; Bidar, Abdel W; Parker, Nicole S; Olsson, Marita; Hockings, Paul D; Lagerstrand, Kerstin M; Olsson, Lars E

2018-03-08

Lung T 1 is a potential translational biomarker of lung disease. The precision and repeatability of variable flip angle (VFA) T 1 mapping using modern 3D ultrashort echo time (UTE) imaging of the whole lung needs to be established before it can be used to assess response to disease and therapy. To evaluate the feasibility of regional lung T 1 quantification with VFA 3D-UTE and to investigate long- and short-term T 1 repeatability in the lungs of naive mice. Prospective preclinical animal study. Eight naive mice and phantoms. 3D free-breathing radial UTE (8 μs) at 4.7T. VFA 3D-UTE T 1 calculations were validated against T 1 values measured with inversion recovery (IR) in phantoms. Lung T 1 and proton density (S 0 ) measurements of whole lung and muscle were repeated five times over 1 month in free-breathing naive mice. Two consecutive T 1 measurements were performed during one of the imaging sessions. Agreement in T 1 between VFA 3D-UTE and IR in phantoms was assessed using Bland-Altman and Pearson 's correlation analysis. The T 1 repeatability in mice was evaluated using coefficient of variation (CV), repeated-measures analysis of variance (ANOVA), and paired t-test. Good T 1 agreement between the VFA 3D-UTE and IR methods was found in phantoms. T 1 in lung and muscle showed a 5% and 3% CV (1255 ± 63 msec and 1432 ± 42 msec, respectively, mean ± SD) with no changes in T 1 or S 0 over a month. Consecutive measurements resulted in an increase of 2% in both lung T 1 and S 0 . VFA 3D-UTE shows promise as a reliable T 1 mapping method that enables full lung coverage, high signal-to-noise ratio (∼25), and spatial resolution (300 μm) in freely breathing animals. The precision of the VFA 3D-UTE method will enable better design and powering of studies. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Exposing Students to Repeat Photography: Increasing Cultural Understanding on a Short-Term Study Abroad

ERIC Educational Resources Information Center

Lemmons, Kelly K.; Brannstrom, Christian; Hurd, Danielle

2014-01-01

Traditionally, repeat photography has been used to analyze land cover change. This paper describes how repeat photography may be used as a tool to enhance the short-term study abroad experience by facilitating cultural interaction and understanding. We present evidence from two cases and suggest a five-step repeat photography method for educators…

Digital repeat analysis; setup and operation.

PubMed

Nol, J; Isouard, G; Mirecki, J

2006-06-01

Since the emergence of digital imaging, there have been questions about the necessity of continuing reject analysis programs in imaging departments to evaluate performance and quality. As a marketing strategy, most suppliers of digital technology focus on the supremacy of the technology and its ability to reduce the number of repeats, resulting in less radiation doses given to patients and increased productivity in the department. On the other hand, quality assurance radiographers and radiologists believe that repeats are mainly related to positioning skills, and repeat analysis is the main tool to plan training needs to up-skill radiographers. A comparative study between conventional and digital imaging was undertaken to compare outcomes and evaluate the need for reject analysis. However, digital technology still being at its early development stages, setting a credible reject analysis program became the major task of the study. It took the department, with the help of the suppliers of the computed radiography reader and the picture archiving and communication system, over 2 years of software enhancement to build a reliable digital repeat analysis system. The results were supportive of both philosophies; the number of repeats as a result of exposure factors was reduced dramatically; however, the percentage of repeats as a result of positioning skills was slightly on the increase for the simple reason that some rejects in the conventional system qualifying for both exposure and positioning errors were classified as exposure error. The ability of digitally adjusting dark or light images reclassified some of those images as positioning errors.

Deletion of internal structured repeats increases the stability of a leucine-rich repeat protein, YopM

PubMed Central

Barrick, Doug

2011-01-01

Mapping the stability distributions of proteins in their native folded states provides a critical link between structure, thermodynamics, and function. Linear repeat proteins have proven more amenable to this kind of mapping than globular proteins. C-terminal deletion studies of YopM, a large, linear leucine-rich repeat (LRR) protein, show that stability is distributed quite heterogeneously, yet a high level of cooperativity is maintained [1]. Key components of this distribution are three interfaces that strongly stabilize adjacent sequences, thereby maintaining structural integrity and promoting cooperativity. To better understand the distribution of interaction energy around these critical interfaces, we studied internal (rather than terminal) deletions of three LRRs in this region, including one of these stabilizing interfaces. Contrary to our expectation that deletion of structured repeats should be destabilizing, we find that internal deletion of folded repeats can actually stabilize the native state, suggesting that these repeats are destabilizing, although paradoxically, they are folded in the native state. We identified two residues within this destabilizing segment that deviate from the consensus sequence at a position that normally forms a stacked leucine ladder in the hydrophobic core. Replacement of these nonconsensus residues with leucine is stabilizing. This stability enhancement can be reproduced in the context of nonnative interfaces, but it requires an extended hydrophobic core. Our results demonstrate that different LRRs vary widely in their contribution to stability, and that this variation is context-dependent. These two factors are likely to determine the types of rearrangements that lead to folded, functional proteins, and in turn, are likely to restrict the pathways available for the evolution of linear repeat proteins. PMID:21764506

Single crystal study of layered UnRhIn3n+2 materials: Case of the novel U2RhIn8 compound

NASA Astrophysics Data System (ADS)

Bartha, Attila; Kratochvílová, M.; Dušek, M.; Diviš, M.; Custers, J.; Sechovský, V.

2015-05-01

We report on the single crystal properties of the novel U2RhIn8 compound studied in the context of parent URhIn5 and UIn3 systems. The compounds were prepared by In self-flux method. U2RhIn8 adopts the Ho2CoGa8-type structure with lattice parameters a=4.6056(6) Å and c=11.9911(15) Å. The behavior of U2RhIn8 strongly resembles that of the related URhIn5 and UIn3 with respect to magnetization, specific heat and resistivity except for magnetocrystalline anisotropy developing with lowering dimensionality in the series UIn3 vs. U2RhIn8 and URhIn5. U2RhIn8 orders antiferromagnetically below TN=117 K and exhibits a slightly enhanced Sommerfeld coefficient γ=47 mJ mol-1 K-2. Magnetic field leaves the value of Néel temperature for both URhIn5 and U2RhIn8 unaffected up to 9 T. On the other hand, TN is increasing when applying hydrostatic pressure up to 3.2 GPa. The character of uranium 5f electron states of U2RhIn8 was studied by first principles calculations based on the density functional theory. The overall phase diagram of U2RhIn8 is discussed in the context of magnetism in the related URhX5 and UX3 (X=In, Ga) compounds.

MicroRNA-223 Enhances Radiation Sensitivity of U87MG Cells In Vitro and In Vivo by Targeting Ataxia Telangiectasia Mutated

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

Liang, Liping; Zhu, Ji; Zaorsky, Nicholas G.

2014-03-15

Purpose: Ataxia telangiectasia mutated (ATM) protein is important in the DNA damage response because it repairs radiation-induced damage in cancers. We examined the effect of microRNA-223 (miR-223), a regulator of ATM expression, on radiation sensitivity of cancer cells. Methods and Materials: Human embryonic kidney 293 T (293T) cells were infected with pLL3.7-miR-223 plasmid to generate the pLL3.7-miR-223 and -empty virus (EV) lentivirus (miR-223 and EV). A dual luciferase assay in which the reporter contained wild-type 3′ untranslated region (UTR) of ATM was performed. U87MG cells were infected with miR-223 or EV to establish the overexpressed stable cell lines (U87-223 or U87-EV, respectively).more » Cells were irradiated in vitro, and dose enhancement ratios at 2 Gy (DER{sub 2}) were calculated. Hind legs of BALB/c athymic mice were injected with U87-223 or U87-EV cells; after 2 weeks, half of the tumors were irradiated. Tumor volumes were tracked for a total of 5 weeks. Results: The dual luciferase reporter assay showed a significant reduction in luciferase activity of 293T cells cotransfected with miR-223 and the ATM 3′UTR compared to that in EV control. Overexpression of miR-223 in U87MG cells showed that ATM expression was significantly downregulated in the U87-223 cells compared to that in U87-EV (ATM/β-actin mRNA 1.0 vs 1.5, P<.05). U87-223 cells were hypersensitive to radiation compared to U87-EV cells in vitro (DER{sub 2} = 1.32, P<.01). Mice injected with miR-223-expressing tumors had almost the same tumors after 3 weeks (1.5 cm{sup 3} vs 1.7 cm{sup 3}). However, irradiation significantly decreased tumor size in miR-223-expressing tumors compared to those in controls (0.033 cm{sup 3} vs 0.829 cm{sup 3}). Conclusions: miR-223 overexpression downregulates ATM expression and sensitizes U87 cells to radiation in vitro and in vivo. MicroRNA-223 may be a novel cancer-targeting therapy, although its cancer- and patient

Microstructure of the irradiated U 3Si 2/Al silicide dispersion fuel

NASA Astrophysics Data System (ADS)

Gan, J.; Keiser, D. D.; Miller, B. D.; Jue, J.-F.; Robinson, A. B.; Madden, J. W.; Medvedev, P. G.; Wachs, D. M.

2011-12-01

The silicide dispersion fuel of U 3Si 2/Al is recognized as the best performance fuel for many nuclear research and test reactors with up to 4.8 gU/cm 3 fuel loading. An irradiated U 3Si 2/Al dispersion fuel ( 235U ˜ 75%) from the high-flux side of a fuel plate (U0R040) from the Reduced Enrichment for Research and Test Reactors (RERTR)-8 test was characterized using transmission electron microscopy (TEM). The fuel was irradiated in the Advanced Test Reactor (ATR) for 105 days. The average irradiation temperature and fission density of the U 3Si 2 fuel particles for the TEM sample are estimated to be approximately 110 °C and 5.4 × 10 27 f/m 3. The characterization was performed using a 200-kV TEM. The U/Si ratio for the fuel particle and (Si + Al)/U for the fuel-matrix-interaction layer are approximately 1.1 and 4-10, respectively. The estimated average diameter, number density and volume fraction for small bubbles (<1 μm) in the fuel particle are ˜94 nm, 1.05 × 10 20 m -3 and ˜11%, respectively. The results and their implication on the performance of the U 3Si 2/Al silicide dispersion fuel are discussed.

VizieR Online Data Catalog: H2 d3{Pi}u excitation by elec

NASA Astrophysics Data System (ADS)

Liu, X.; Shemansky, D. E.; Yoshii, J.; Johnson, P. V.; Malone, C. P.; Ajello, J. M.

2016-05-01

Electron-impact excitation of H2 triplet states plays an imp role in the heating of outer planet upper thermospheres. The d3{Pi}u state is the third ungerade triplet state, and the d3{Pi}u-a3{Sigma}g+ emission is the largest cascade channel for the a3{Sigma}g+ state. Accurate energies of the d3{Pi}u-(v, J) levels are calculated from an ab initio potential energy curve. Radiative lifetimes of the d3{Pi}u(v,J) levels are obtained by an accurate evaluation of the d3{Pi}u-a3{Sigma}g+ transition probabilities. The emission yields are determined from experimental lifetimes and calculated radiative lifetimes and are further verified by comparing experimental and synthetic d3{Pi}u-a3{Sigma}g+ spectra at 20eV impact energy. Spectral analysis revealed that multipolar components beyond the dipolar term are required to model the X1{Sigma}g+-d3{Pi}u excitation, and significant cascade excitation occurs at the d3{Pi}u (v=0,1) levels. Kinetic energy (Ek) distributions of H atoms produced via predissociation of the 3{Pi}u state and the d3{Pi}u-a3{Sigma}g+-b3{Sigma}u+ cascade dissociative emission are obtained. Predissociation of the d3{Pi}u state produces H atoms with an average Ek of 2.3+/-0.4 eV/atom, while the Ekdistribution of the d3{Pi}u-a3{Sigma}g+-b3{Sigma}u+ channel is similar to that of the X1{Sigma}g+-a3{Sigma}g+-b3{Sigma}u+ channel and produces H(1s) atoms with an average Ek of 1.15+/-0.05eV/atom. On average, each H2 excited to the d3{Pi}u state in an H2-dominated atmosphere deposits 3.3+/-0.4eV into the atmosphere, while each H2directly excited to the a3{Sigma}g+ state gives 2.2-2.3eV to the atmosphere. The spectral distribution of the calculated a3{Sigma}g+-b3{Sigma}u+ continuum emission due to the X1{Sigma}g+-d3{Pi}u excitation is significantly different from that of direct a3{Sigma}g+ excitation. (2 data files).

Lightning and anthropogenic NOx sources over the U.S. and the western North Atlantic Ocean: Impact on tropospheric O3 from space-borne observations

NASA Astrophysics Data System (ADS)

Choi, Y.; Eldering, A.; Osterman, G.; Wang, Y.; Cunnold, D.; Yang, Q.; Bucsela, E.; Pickering, K.

2008-12-01

We use the Regional chEmical trAnsport Model (REAM) to analyze the contributions of lightning and anthropogenic NOx on ozone concentrations over the U.S. and the western North Atlantic Ocean from June to August 2005. Tropospheric NO2 columns from OMI, tropospheric O3 columns derived from OMI and MLS measurements, and vertical O3 profiles from TES over the region are used in the analysis. With a 50% reduction in the industrial and electrical power generation NOx emissions in the 23 eastern states over the U.S. from 1999 EPA NEI and a parameterization of lightning-produced NOx based on concurrent NLDN, CAPE, and cloud mass flux data, REAM generally captures the spatial distribution of lightning flash rates and OMI NO2 and OMI-MLS O3 column enhancements with high correlation coefficients (0.6-0.9). The model results show that over the U.S., the contribution of surface NOx emissions to summertime tropospheric O3 declines from 47% to 41% due to the reduced emissions. The contribution of surface NOx emissions becomes similar to that of stratospheric transport over the U.S., with the additional being the dramatic reduction in the relative impact of fossil-fuel NOx emissions over continental outflow regions. In the convective outflow regions over the Gulf of Mexico and the western North Atlantic, the contribution of lightning NOx production on tropospheric O3 in the summer is larger than that of anthropogenic NOx emissions with mean differences of 5% to 25%. The impact of NOx produced by lightning is becoming larger as fossil-fuel combustion NOx emissions decrease. After the onset of the North American monsoon, lightning-derived upper tropospheric O3 enhancements in July and August are shown over the convective outflow regions from REAM simulated and TES measured O3 vertical profiles. This result suggests that TES measurements have a potential to constrain lightning-derived tropospheric O3 enhancements, which may play a critical role in controlling climate.

White light scanner-based repeatability of 3-dimensional digitizing of silicon rubber abutment teeth impressions

PubMed Central

Jeon, Jin-Hun; Lee, Kyung-Tak; Kim, Hae-Young; Kim, Ji-Hwan

2013-01-01

PURPOSE The aim of this study was to evaluate the repeatability of the digitizing of silicon rubber impressions of abutment teeth by using a white light scanner and compare differences in repeatability between different abutment teeth types. MATERIALS AND METHODS Silicon rubber impressions of a canine, premolar, and molar tooth were each digitized 8 times using a white light scanner, and 3D surface models were created using the point clouds. The size of any discrepancy between each model and the corresponding reference tooth were measured, and the distribution of these values was analyzed by an inspection software (PowerInspect 2012, Delcamplc., Birmingham, UK). Absolute values of discrepancies were analyzed by the Kruskal-Wallis test and multiple comparisons (α=.05). RESULTS The discrepancy between the impressions for the canine, premolar, and molar teeth were 6.3 µm (95% confidence interval [CI], 5.4-7.2), 6.4 µm (95% CI, 5.3-7.6), and 8.9 µm (95% CI, 8.2-9.5), respectively. The discrepancy of the molar tooth impression was significantly higher than that of other tooth types. The largest variation (as mean [SD]) in discrepancies was seen in the premolar tooth impression scans: 26.7 µm (95% CI, 19.7-33.8); followed by canine and molar teeth impressions, 16.3 µm (95% CI, 15.3-17.3), and 14.0 µm (95% CI, 12.3-15.7), respectively. CONCLUSION The repeatability of the digitizing abutment teeth's silicon rubber impressions by using a white light scanner was improved compared to that with a laser scanner, showing only a low mean discrepancy between 6.3 µm and 8.9 µm, which was in an clinically acceptable range. Premolar impression with a long and narrow shape showed a significantly larger discrepancy than canine and molar impressions. Further work is needed to increase the digitizing performance of the white light scanner for deep and slender impressions. PMID:24353885

MAOA-uVNTR polymorphism may modify the protective effect of ALDH2 gene against alcohol dependence in antisocial personality disorder.

PubMed

Lee, Sheng-Yu; Hahn, Cheng-Yi; Lee, Jia-Fu; Chen, Shiou-Lan; Chen, Shih-Heng; Yeh, Tzung Lieh; Kuo, Po-Hsiu; Lee, I Hui; Yang, Yen Kuang; Huang, San-Yuan; Ko, Huei-Chen; Lu, Ru-Band

2009-06-01

Antisocial alcoholism is related to dopamine and serotonin which are catalyzed by monoamine oxidase A (MAOA) and acetaldehyde dehydrogenase 2 (ALDH2). The objective of this study is to determine whether the interaction between the MAOA and the ALDH2 genes is associated with subjects with antisocial personality disorder (ASPD) having alcoholism. A total of 294 Han Chinese men in Taiwan including 132 ASPD with alcoholism (Antisocial ALC) and 162 without alcoholism (Antisocial Non-ALC) were recruited in this study. Alcohol dependence and ASPD were diagnosed according to DSM-IV criteria. Genotypes of ALDH2 and MAOA-uVNTR were determined using PCR-RFLP. A significant difference of ALDH2 polymorphisms (p = 3.39E-05), but not of MAOA, was found among the 2 study groups. However, only after the stratification of the MAOA-uVNTR (variable number of tandem repeat located upstream) 3-repeat, a significant association between Antisocial Non-ALC and ALDH2*1/*2 or *2/*2 genotypes was shown (p = 1.46E-05; odds ratio = 3.913); whereas stratification of MAOA-uVNTR 4-repeat revealed no association. Multiple logistic regression analysis further revealed significant interaction of MAOA and ALDH2 gene in antisocial ALC (odds ratio = 2.927; p = 0.032). The possible interaction of MAOA and ALDH2 gene is associated with Antisocial ALC in Han Chinese males in Taiwan. However, the protective effects of the ALDH2*2 allele against alcoholism might disappear in subjects with ASPD and carrying MAOA-uVNTR 4-repeat allele in the Han Chinese male population.

Nuclear Retention Elements of U3 Small Nucleolar RNA

PubMed Central

Speckmann, Wayne; Narayanan, Aarthi; Terns, Rebecca; Terns, Michael P.

1999-01-01

The processing and methylation of precursor rRNA is mediated by the box C/D small nucleolar RNAs (snoRNAs). These snoRNAs differ from most cellular RNAs in that they are not exported to the cytoplasm. Instead, these RNAs are actively retained in the nucleus where they assemble with proteins into mature small nucleolar ribonucleoprotein particles and are targeted to their intranuclear site of action, the nucleolus. In this study, we have identified the cis-acting sequences responsible for the nuclear retention of U3 box C/D snoRNA by analyzing the nucleocytoplasmic distributions of an extensive panel of U3 RNA variants after injection of the RNAs into Xenopus oocyte nuclei. Our data indicate the importance of two conserved sequence motifs in retaining U3 RNA in the nucleus. The first motif is comprised of the conserved box C′ and box D sequences that characterize the box C/D family. The second motif contains conserved box sequences B and C. Either motif is sufficient for nuclear retention, but disruption of both motifs leads to mislocalization of the RNAs to the cytoplasm. Variant RNAs that are not retained also lack 5′ cap hypermethylation and fail to associate with fibrillarin. Furthermore, our results indicate that nuclear retention of U3 RNA does not simply reflect its nucleolar localization. A fragment of U3 containing the box B/C motif is not localized to nucleoli but retained in coiled bodies. Thus, nuclear retention and nucleolar localization are distinct processes with differing sequence requirements. PMID:10567566

Analysis of pellet cladding interaction and creep of U 3SIi2 fuel for use in light water reactors

NASA Astrophysics Data System (ADS)

Metzger, Kathryn E.

Following the accident at the Fukushima plant, enhancing the accident tolerance of the light water reactor (LWR) fleet became a topic of serious discussion. Under the direction of congress, the DOE office of Nuclear Energy added accident tolerant fuel development as a primary component to the existing Advanced Fuels Program. The DOE defines accident tolerant fuels as fuels that "in comparison with the standard UO2- Zircaloy system currently used by the nuclear industry, can tolerate loss of active cooling in the reactor core for a considerably longer time period (depending on the LWR system and accident scenario) while maintaining or improving the fuel performance during normal operations, operational transients, as well as design-basis and beyond design-basis events." To be economically viable, proposed accident tolerant fuels and claddings should be backward compatible with LWR designs, provide significant operating cost improvements such as power uprates, increased fuel burnup, or increased cycle length. In terms of safety, an alternative fuel pellet must have resistance to water corrosion comparable to UO2, thermal conductivity equal to or larger than that of UO2, and a melting temperature that allows the material to remain solid under power reactor conditions. Among the candidates, U3Si2 has a number of advantageous thermophysical properties, including; high density, high thermal conductivity at room temperature, and a high melting temperature. These properties support its use as an accident tolerant fuel while its high uranium density is capable of supporting uprates to the LWR fleet. This research characterizes U3Si2 pellets and analyzes U3Si2 under light water reactor conditions using the fuel performance code BISON. While some thermophysical properties for U3Si2 have been found in the literature, the irradiation behavior is sparse and limited to experience with dispersion fuels. Accordingly, the creep behavior for U3Si2 has been unknown, making it

On some factors affecting the nonstoichiometry in U 3O 8

NASA Astrophysics Data System (ADS)

Fujino, Takeo; Tagawa, Hiroaki; Adachi, Takeo

1981-03-01

The nonstoichiometry of U 3O 8 was studied under various conditions. The {O}/{U} atom ratios obtained by the oxidation of uranium metal in air followed by cooling with moderate rates (method 1) are 2.67 ± 0.01 in the temperature range 700 900°C and 2.662 ± 0.005 at 1000°C and are generally larger than the ratio by thermogravimetry. If the oxidation was carried out in a crucible with a lid, a compositional peak was observed at 900 950°C, which did not appear for the U 3O 8 samples from UO 2. The U 3O 8 made from UO 2 by method 1 have {O}/{U} ratios 2.655 ± 0.005 (700° C), 2.653 ± 0.004 (800° C), 2.648 ± 0.004 (900° C) and 2.645 ± 0.003 (1000° C). Differences were observed in the O/U ratios of heating and cooling series. X-ray diffraction analysis showed several additional peaks other than those of α-U 3O 8 for the samples which exhibited the compositional peak.

U.S. Rice: Enhancing human health.

USDA-ARS?s Scientific Manuscript database

A vision of the U.S. rice industry is to improve human health through the development of germplasm and technologies for products that capture the unique nutritional benefits of the rice grain. This paper gives an overview of U.S. rice production and markets. New product trends and introductions in...

Radiation effects on interface reactions of U/Fe, U/(Fe+Cr), and U/(Fe+Cr+Ni)

DOE PAGES

Shao, Lin; Chen, Di; Wei, Chaochen; ...

2014-10-01

We study the effects of radiation damage on interdiffusion and intermetallic phase formation at the interfaces of U/Fe, U/(Fe + Cr), and U/(Fe + Cr + Ni) diffusion couples. Magnetron sputtering is used to deposit thin films of Fe, Fe + Cr, or Fe + Cr + Ni on U substrates to form the diffusion couples. One set of samples are thermally annealed under high vacuum at 450 C or 550 C for one hour. A second set of samples are annealed identically but with concurrent 3.5 MeV Fe++ ion irradiation. The Fe++ ion penetration depth is sufficient to reachmore » the original interfaces. Rutherford backscattering spectrometry analysis with high fidelity spectral simulations is used to obtain interdiffusion profiles, which are used to examine differences in U diffusion and intermetallic phase formation at the buried interfaces. For all three diffusion systems, Fe++ ion irradiations enhance U diffusion. Furthermore, the irradiations accelerate the formation of intermetallic phases. In U/Fe couples, for example, the unirradiated samples show typical interdiffusion governed by Fick’s laws, while the irradiated ones show step-like profiles influenced by Gibbs phase rules.« less

The potential impact on farmer health of enhanced export horticultural trade between the U.K. and Uganda.

PubMed

Cross, Paul; Edwards, Rhiannon T; Nyeko, Philip; Edwards-Jones, Gareth

2009-05-01

The export of vegetables from African countries to European markets presents consumers with an ethical dilemma: should they support local, but relatively well-off farmers, or poorer farmers from distant countries? This paper considers the issue of farm worker health in the U.K. and Uganda, and considers the dilemma facing U.K. consumers if Uganda achieves their aim of exporting more vegetables to the U.K. Self-reported health scores of 1,200 farm workers in the U.K. and Uganda were measured with the internationally recognised SF-36 questionnaire and compared to an international population norm. The age-corrected health status of U.K. farm workers was significantly lower than the population norm, whereas Ugandans scored significantly higher (indicating good health) for physical health and lower for mental health. If Ugandan produce enters U.K. markets, then consumers may wish to consider both the potential benefits that enhanced trade could offer Ugandan farmers compared with its impacts on U.K. workers.

Revisiting the TALE repeat.

PubMed

Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

2014-04-01

Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

Freely Chosen Index Finger Tapping Frequency Is Increased in Repeated Bouts of Tapping.

PubMed

Hansen, Ernst Albin; Ebbesen, Brian Duborg; Dalsgaard, Ane; Mora-Jensen, Mark Holten; Rasmussen, Jakob

2015-01-01

Healthy individuals (n = 40) performed index finger tapping at freely chosen frequency during repeated bouts and before and after near-maximal muscle action consisting of 3 intense flexions of the index finger metacarpal phalangeal joint. One experiment showed, unexpectedly, that a bout of tapping increased the tapping frequency in the subsequent bout. Thus, a cumulating increase of 8.2 ± 5.4% (p < .001) occurred across 4 bouts, which were all separated by 10 min rest periods. Follow-up experiments revealed that tapping frequency was still increased in consecutive bouts when rest periods were extended to 20 min. Besides, near-maximal muscle activation, followed by 5 min rest, did not affect the tapping frequency. In conclusion, freely chosen tapping frequency was increased in repeated bouts of tapping, which were separated by 10-20 min rest periods. The observed phenomenon is suggested to be termed repeated bout rate enhancement.

19 CFR 10.619 - Repeated false or unsupported preference claims.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Republic-Central America-United States Free Trade Agreement Origin Verifications and Determinations § 10... 19 Customs Duties 1 2010-04-01 2010-04-01 false Repeated false or unsupported preference claims. 10.619 Section 10.619 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND...

Repeated 28-day oral toxicity study of vinclozolin in rats based on the draft protocol for the "Enhanced OECD Test Guideline No. 407" to detect endocrine effects.

PubMed

Shin, Jae-Ho; Moon, Hyun Ju; Kim, Tae Sung; Kang, Il Hyun; Ki, Ho Yeon; Choi, Kwang Sik; Han, Soon Young

2006-09-01

We performed a 28-day repeated-dose toxicity study of vinclozolin, a widely used fungicide, based on the draft protocol of the "Enhanced OECD Test Guideline 407" (Enhanced TG407) to investigate whether vinclozolin has endocrine-mediated properties according to this assay. Seven-week-old SD rats were administered with vinclozolin daily by oral gavage at dose rates of 0, 3.125, 12.5, 50 and 200 mg/kg/day for at least 28 days. The vinclozolin-treated male rats showed a reduction of epididymis and accessory sex organ weights and an alteration of hormonal patterns. A slight prolongation of the estrous cycle and changes in the estrogen/testosterone ratio and luteinizing hormone level were observed in vinclozolin-treated female rats. Thyroxin concentrations were decreased and thyroid-stimulating hormone concentrations were increased in both sexes; however, there were no compound-related microscopic lesions in the thyroid gland or changes in the thyroid weight. The endocrine-related effects of vinclozolin could be detected by the parameters examined in the present study based on the OECD protocol, suggesting the Enhanced TG407 protocol should be a suitable screening test for the detection of endocrine-mediated effects of chemicals.

X-ray analysis of the effect of the 5-HT3 receptor antagonist granisetron on gastrointestinal motility in rats repeatedly treated with the antitumoral drug cisplatin.

PubMed

Vera, Gema; López-Pérez, Ana Esther; Martínez-Villaluenga, María; Cabezos, Pablo Antonio; Abalo, Raquel

2014-08-01

Cancer chemotherapy is associated with the development of numerous adverse effects, including nausea, emesis and other alterations in gastrointestinal (GI) motility. The administration of 5-HT3 receptor antagonists has provided a clinical advance in the treatment of chemotherapy-induced vomiting but these drugs lose efficacy throughout chronic treatment. The effects of these drugs in experimental animals under chronic administration are not well known. Our aim was to study, using radiographic methods, the effect of the 5-HT3 receptor antagonist granisetron on GI dysmotility induced in the rat by repeated cisplatin administration. First, invasive methods were used to select a dose of granisetron capable of reducing increased stomach weight due to acute cisplatin administration (6 mg/kg, ip). Second, rats received two intraperitoneal (ip) injections once a week for 4 weeks: granisetron (1 mg/kg, ip) or saline and, thirty min later, saline or cisplatin (2 mg/kg, ip). Body weight gain was measured throughout treatment. Radiological techniques were used to determine the acute (after first dose) and chronic (after last dose) effects of cisplatin and/or granisetron on GI motility. Repeated cisplatin-induced weight loss which granisetron did not prevent. Gastric emptying was delayed after the first cisplatin administration. Granisetron completely prevented this effect. After weekly administration, cisplatin-induced gastric dysmotility was enhanced and granisetron was not capable of completely preventing this effect. Granisetron prevents gastric emptying alterations, but its efficacy decreases throughout antineoplastic treatment. This might be due to the enhanced effect of cisplatin.

Environmental stress induces trinucleotide repeat mutagenesis in human cells.

PubMed

Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A; Yotnda, Patricia; Wilson, John H

2015-03-24

The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)-the cause of multiple human diseases-have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential.

Salivary cortisol and α-amylase responses to repeated bouts of downhill running.

PubMed

Mckune, Andrew J; Bach, Christopher W; Semple, Stuart J; Dyer, Barry J

2014-01-01

To determine the hypothalamic-pituitary-adrenal (HPA) axis and sympathoadrenal (SA) system response to repeated bouts of downhill running. Eleven active but untrained males (age: 19.7 ± 0.4 y; VO2peak 47.8 ± 3.6 ml/kg/min) performed two 60 min bouts of downhill running (-13.5% gradient), separated by 14 days, at a speed eliciting 75% of their VO2peak on a level grade. Saliva samples were collected before (baseline), after, and every hour for 12 h and every 24 h for 6 days after each run. Salivary cortisol and α-amylase levels were measured as markers of the HPA axis and SA response, respectively. Results were analyzed using repeated measures ANOVA (12 h period: 2 × 14; 24 h intervals 2 × 7, P ≤ 0.05) with Tukey post-hoc tests where appropriate. Paired samples t-tests were used to compare collapsed data vs. baseline measurements. There were no significant group × time interactions for cortisol or α-amylase for the hourly samples up to 12 h after each run, nor for the 24 h samples up to 6 days later. The 24 h samples for α-amylase showed a significant group effect between runs (Run 1: 69.77 ± 7.68 vs. Run 2: 92.19 ± 7.67 U/ml; P = 0.04). Significant time effects were measured for both cortisol (decreased 2 h to 12 h post-run) and α-amylase (elevated immediately after, 1 h and 2 h post-run) (P < 0.001). The 24 h period group effect for salivary α-amylase suggested an adaptation in the sympathoadrenal system that may alter the systemic inflammatory response to exercise-induced muscle damage but may also reflect enhanced mucosal immunity. © 2014 Wiley Periodicals, Inc.

Effects of repeated exposure of rats to JP-5 or JP-8 jet fuel vapor on neurobehavioral capacity and neurotransmitter levels.

PubMed

Rossi, J; Nordholm, A F; Carpenter, R L; Ritchie, G D; Malcomb, W

2001-07-20

The U.S. Naval Service is anticipating transition from the nearly exclusive use of JP-5 jet fuel to predominant use of JP-8, consistent with the primary utilization by the U.S. Army, U.S. Air Force, and the militaries of most NATO countries. To compare the relative risk of repeated exposure to JP-5 versus JP-8 vapor, groups of 32 male Sprague-Dawley rats each were exposed for 6 h/d, 5 d/wk for 6 wk (180 h) to JP-8 jet fuel vapor (1,000 +/- 10% mg/m3), IP-5 vapor (1,200 +/- 10% mg/m3), or room air control conditions. Following a 65-d rest period, rats completed 10 tests selected from the Neurobehavioral Toxicity Assessment Battery (NTAB) to evaluate changes in performance capacity. Repeated exposure to JP-5 resulted in significant effects on only one test, forelimb grip strength (FGS), while exposure to JP-8 vapor resulted in a significant difference versus controls on appetitive reinforcer approach sensitization (ARAS). Rats were further evaluated for concentrations of major neurotransmitters and metabolites in five brain regions and in the blood serum. Levels of dopamine, the dopamine metabolite dihydroxyphenylacetic acid (DOPAC), and the serotonin metabolite homovanillic acid (HVA) were significantly modulated in various brain regions, as measured 85+ d postexposure. Similarly, serum levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were differentially modulated following JP-8 or JP-5 exposure. Results are compared to previously published research evaluating the neurotoxicity of repeated exposure to other hydrocarbon fuels and solvents.

Highly sensitive detection of individual HEAT and ARM repeats with HHpred and COACH.

PubMed

Kippert, Fred; Gerloff, Dietlind L

2009-09-24

HEAT and ARM repeats occur in a large number of eukaryotic proteins. As these repeats are often highly diverged, the prediction of HEAT or ARM domains can be challenging. Except for the most clear-cut cases, identification at the individual repeat level is indispensable, in particular for determining domain boundaries. However, methods using single sequence queries do not have the sensitivity required to deal with more divergent repeats and, when applied to proteins with known structures, in some cases failed to detect a single repeat. Testing algorithms which use multiple sequence alignments as queries, we found two of them, HHpred and COACH, to detect HEAT and ARM repeats with greatly enhanced sensitivity. Calibration against experimentally determined structures suggests the use of three score classes with increasing confidence in the prediction, and prediction thresholds for each method. When we applied a new protocol using both HHpred and COACH to these structures, it detected 82% of HEAT repeats and 90% of ARM repeats, with the minimum for a given protein of 57% for HEAT repeats and 60% for ARM repeats. Application to bona fide HEAT and ARM proteins or domains indicated that similar numbers can be expected for the full complement of HEAT/ARM proteins. A systematic screen of the Protein Data Bank for false positive hits revealed their number to be low, in particular for ARM repeats. Double false positive hits for a given protein were rare for HEAT and not at all observed for ARM repeats. In combination with fold prediction and consistency checking (multiple sequence alignments, secondary structure prediction, and position analysis), repeat prediction with the new HHpred/COACH protocol dramatically improves prediction in the twilight zone of fold prediction methods, as well as the delineation of HEAT/ARM domain boundaries. A protocol is presented for the identification of individual HEAT or ARM repeats which is straightforward to implement. It provides high

Highly Sensitive Detection of Individual HEAT and ARM Repeats with HHpred and COACH

PubMed Central

Kippert, Fred; Gerloff, Dietlind L.

2009-01-01

Background HEAT and ARM repeats occur in a large number of eukaryotic proteins. As these repeats are often highly diverged, the prediction of HEAT or ARM domains can be challenging. Except for the most clear-cut cases, identification at the individual repeat level is indispensable, in particular for determining domain boundaries. However, methods using single sequence queries do not have the sensitivity required to deal with more divergent repeats and, when applied to proteins with known structures, in some cases failed to detect a single repeat. Methodology and Principal Findings Testing algorithms which use multiple sequence alignments as queries, we found two of them, HHpred and COACH, to detect HEAT and ARM repeats with greatly enhanced sensitivity. Calibration against experimentally determined structures suggests the use of three score classes with increasing confidence in the prediction, and prediction thresholds for each method. When we applied a new protocol using both HHpred and COACH to these structures, it detected 82% of HEAT repeats and 90% of ARM repeats, with the minimum for a given protein of 57% for HEAT repeats and 60% for ARM repeats. Application to bona fide HEAT and ARM proteins or domains indicated that similar numbers can be expected for the full complement of HEAT/ARM proteins. A systematic screen of the Protein Data Bank for false positive hits revealed their number to be low, in particular for ARM repeats. Double false positive hits for a given protein were rare for HEAT and not at all observed for ARM repeats. In combination with fold prediction and consistency checking (multiple sequence alignments, secondary structure prediction, and position analysis), repeat prediction with the new HHpred/COACH protocol dramatically improves prediction in the twilight zone of fold prediction methods, as well as the delineation of HEAT/ARM domain boundaries. Significance A protocol is presented for the identification of individual HEAT or ARM repeats

Photometric Repeatability of Scanned Imagery: UVIS

NASA Astrophysics Data System (ADS)

Shanahan, Clare E.; McCullough, Peter; Baggett, Sylvia

2017-08-01

We provide the preliminary results of a study on the photometric repeatability of spatial scans of bright, isolated white dwarf stars with the UVIS channel of the Wide Field Camera 3 (WFC3) on the Hubble Space Telescope (HST). We analyze straight-line scans from the first pair of identical orbits of HST program 14878 to assess if sub 0.1% repeatability can be attained with WFC3/UVIS. This study is motivated by the desire to achieve better signal-to-noise in the UVIS contamination and stability monitor, in which observations of standard stars in staring mode have been taken from the installation of WFC3 in 2009 to the present to assess temporal photometric stability. Higher signal to noise in this program would greatly benefit the sensitivity to detect contamination, and to better characterize the observed small throughput drifts over time. We find excellent repeatability between identical visits of program 14878, with sub 0.1% repeatability achieved in most filters. These! results support the initiative to transition the staring mode UVIS contamination and photometric stability monitor from staring mode images to spatial scans.

Kodak Skills Enhancement Program. U.S. Department of Education National Workplace Literacy Project. Final Report.

ERIC Educational Resources Information Center

Beaudin, Bart P.

The Kodak Skills Enhancement program was a workplace literacy project funded through the U.S. Department of Education's National Workplace Literacy Program. The project goals were as follows: (1) establish a positive climate within the Kodak corporate environment to ensure program effectiveness by garnering support at all levels; (2) determine the…

Tyms double (2R) and triple repeat (3R) confers risk for human oral squamous cell carcinoma.

PubMed

Bezerra, Alexandre Medeiros; Sant'Ana, Thalita Araújo; Gomes, Adriana Vieira; de Lacerda Vidal, Aurora Karla; Muniz, Maria Tereza Cartaxo

2014-12-01

The oral cancer is responsible for approximately 3 % of cases of cancer in Brazil. Epidemiological studies have associated low folate intake with an increased risk of epithelial cancers, including oral cancer. Folic acid has a key role in DNA synthesis, repair, methylation and this is the basis of explanations for a putative role for folic acid in cancer prevention. The role of folic acid in carcinogenesis may be modulated by polymorphism C677T in MTHFR and tandem repeats 2R/3R in the promoter site of TYMS gene that are related to decreased enzymatic activity and quantity and availability of the enzyme, respectively. These events cause a decrease in the synthesis, repair and DNA methylation, which can lead to a disruption in the expression of tumor suppressor genes as TP53. The objective of this study was investigate the distribution of polymorphisms C677T and tandem repeats 2R/3R associated with the development of oral squamous cell carcinoma (OSCC). 53 paraffin-embedded samples from patients who underwent surgery but are no longer at the institution and 43 samples collected by method of oral exfoliation by cytobrush were selected. 132 healthy subjects were selected by specialists at the dental clinics of the Faculdade de Odontologia de Pernambuco-FOP. The MTHFR genotyping was performed by PCR-RFLP, and the TYMS genotyping was performed by conventional PCR. Fisher's Exact test at significant level of 5 %. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to measure the strength of association between genotype frequency and OSCC development. The results were statistically significant for the tandem repeats of the TYMS gene (p = 0.015). The TYMS 2R3R genotype was significantly associated with the development of OSCC (OR = 3.582; 95 % CI 1.240-10.348; p = 0.0262) and also the genotype 3R3R (OR = 3.553; 95 % CI 1.293-9.760; p = 0.0345). When analyzed together, the TYMS 2R3R + 3R3R genotypes also showed association (OR = 3.518; 95 % CI 11.188-10.348; p

Theoretical Study of the B(sup 3) Sigma(sup -, sub u) - X(sup3)Sigma(sub g, sup -) and B"(sup 3)Pi(sub u) - X(sup 3)Sigma(sub g, sup -) Band Systems of S(sub 2)

NASA Technical Reports Server (NTRS)

Pradhan, Atul D.; Partridge, Harry; Langhoff, Stephen R. (Technical Monitor)

1995-01-01

Multireference configuration-interaction (MRCI) wavefunctions and potential energy curves have been calculated for the X(sup 3)Sigma(sub g,sup -), B(sup 3)Sigma(sub u, Sup -) and B"(sup 3)Pi((sub u) states of S(sub 2) using correlation consistent Gaussian basis sets. These wavefunctions are utilized to compute the the transition dipole moments of the B(sup 3)Sigma(sub g, sup -) - X(sup 3) Sigma(sub g, sup -) and B"(sup 3)Pi(sub u) - X(sup 3)Sigma(sub g, sup -) systems. Oscillator strengths, transition probabilities, and radiative lifetimes are computed for the X-B system and comparison is made with experimental data.

Repeated Solid-state Dewetting of Thin Gold Films for Nanogap-rich Plasmonic Nanoislands.

PubMed

Kang, Minhee; Park, Sang-Gil; Jeong, Ki-Hun

2015-10-15

This work reports a facile wafer-level fabrication for nanogap-rich gold nanoislands for highly sensitive surface enhanced Raman scattering (SERS) by repeating solid-state thermal dewetting of thin gold film. The method provides enlarged gold nanoislands with small gap spacing, which increase the number of electromagnetic hotspots and thus enhance the extinction intensity as well as the tunability for plasmon resonance wavelength. The plasmonic nanoislands from repeated dewetting substantially increase SERS enhancement factor over one order-of-magnitude higher than those from a single-step dewetting process and they allow ultrasensitive SERS detection of a neurotransmitter with extremely low Raman activity. This simple method provides many opportunities for engineering plasmonics for ultrasensitive detection and highly efficient photon collection.

Two tandemly repeated telomere-associated sequences in Nicotiana plumbaginifolia.

PubMed

Chen, C M; Wang, C T; Wang, C J; Ho, C H; Kao, Y Y; Chen, C C

1997-12-01

Two tandemly repeated telomere-associated sequences, NP3R and NP4R, have been isolated from Nicotiana plumbaginifolia. The length of a repeating unit for NP3R and NP4R is 165 and 180 nucleotides respectively. The abundance of NP3R, NP4R and telomeric repeats is, respectively, 8.4 x 10(4), 6 x 10(3) and 1.5 x 10(6) copies per haploid genome of N. plumbaginifolia. Fluorescence in situ hybridization revealed that NP3R is located at the ends and/or in interstitial regions of all 10 chromosomes and NP4R on the terminal regions of three chromosomes in the haploid genome of N. plumbaginifolia. Sequence homology search revealed that not only are NP3R and NP4R homologous to HRS60 and GRS, respectively, two tandem repeats isolated from N. tabacum, but that NP3R and NP4R are also related to each other, suggesting that they originated from a common ancestral sequence. The role of these repeated sequences in chromosome healing is discussed based on the observation that two to three copies of a telomere-similar sequence were present in each repeating unit of NP3R and NP4R.

VizieR Online Data Catalog: H2, D2, and HD c3Πu;

NASA Astrophysics Data System (ADS)

Liu, X.; Shemansky, D. E.; Yoshii, J.; Liu, M. J.; Johnson, P. V.; Malone, C. P.; Khakoo, M. A.

2017-11-01

The c3{Pi}u state of the hydrogen molecule has the triplet-state excitation cross-section, and plays an important role in the heating of the upper thermospheres of outer planets by electron excitation. Precise energies of the H2, D2, and HD c3{Pi}u-(v,N) levels are calculated from highly accurate ab initio potential energy curves that include relativistic, radiative, and empirical non-adiabatic corrections. The emission yields are determined from predissociation rates and refined radiative transition probabilities. The excitation function and excitation cross-section of the c3{Pi}u state are extracted from previous theoretical calculations and experimental measurements. The emission cross-section is determined from the calculated emission yield and the extracted excitation cross-section. The kinetic energy (Ek) distributions of H atoms produced via the predissociation of the c3{Pi}u state, the c3{Pi}u--b3{Sigma}u+ dissociative emission by the magnetic dipole and electric quadrupole, and the c3{Pi}u-a3{Sigma}g+-b3{Sigma}u+ cascade dissociative emission by the electric dipole are obtained. The predissociation of the c3{Pi}u+ and c3{Pi}u- states both produce H(1s) atoms with an average Ek of ~4.1eV/atom, while the c3{Pi}u--b3{Sigma}u+ dissociative emissions by the magnetic dipole and electric quadrupole give an average Ek of ~1.0 and ~0.8eV/atom, respectively. The c3{Pi}u-a3{Sigma}g+-b3{Sigma}u+ cascade and dissociative emission gives an average Ek of ~1.3 eV/atom. On average, each H2 excited to the c3{Pi}u state in an H2-dominated atmosphere deposits ~7.1eV into the atmosphere while each H2 directly excited to the a3{Sigma}g+ and d3{Pi}u states contribute ~2.3 and ~3.3eV, respectively, to the atmosphere. The spectral distribution of the calculated continuum emission arising from the X1{Sigma}g+-c3{Pi}u excitation is significantly different from that of direct a3{Sigma}g+ or d3{Pi}u excitations. (5 data files).

Historical Material Analysis of DC745U Pressure Pads

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

Ortiz-Acosta, Denisse

As part of the Enhance Surveillance mission, it is the goal to provide suitable lifetime assessment of stockpile materials. This report is an accumulation of historical publication on the DC745U material and their findings. It is the intention that the B61 LEP program uses this collection of data to further develop their understanding and potential areas of study. DC745U is a commercially available silicone elastomer consisting of dimethyl, methyl-phenyl, and methyl-vinyl siloxane repeat units. Originally, this material was manufactured by Dow Corning as Silastic{reg_sign} DC745U at their manufacturing facility in Kendallville, IN. Recently, Dow Corning shifted this material to themore » Xiameter{reg_sign} brand product line. Currently, DC745U is available through Xiameter{reg_sign} or Dow Corning's distributor R. D. Abbott Company. DC745U is cured using 0.5 wt% vinyl-specific peroxide curing agent known as Luperox 101 or Varox DBPH-50. This silicone elastomer is used in numerous parts, including two major components (outer pressure pads and aft cap support) in the W80 and as pressure pads on the B61. DC745U is a proprietary formulation, thus Dow Corning provides limited information on its composition and properties. Based on past experience with Dow Corning, DC745U is at risk of formulation changes without notification to the costumer. A formulation change for DC745U may have a significant impact because the network structure is a key variable in determining material properties. The purpose of this report is to provide an overview of historical DC745U studies and identify gaps that need to be addressed in future work. Some of the previous studies include the following: 1. Spectroscopic characterization of raw gum stock. 2. Spectroscopic, thermal, and mechanical studies on cured DC745U. 3. Nuclear Magnetic Resonance (NMR) and solvent swelling studies on DC745U with different crosslink densities. 4. NMR, solvent swelling, thermal, and mechanical studies on

Two-Fluid Extensions to the M3D CDX-U Validation Study

NASA Astrophysics Data System (ADS)

Breslau, J.; Strauss, H.; Sugiyama, L.

2005-10-01

As part of a cross-code verification and validation effort, both the M3D code [1] and the NIMROD code [2] have qualitatively reproduced the nonlinear behavior of a complete sawtooth cycle in the CDX-U tokamak, chosen for the study because its low temperature and small size puts it in a parameter regime easily accessible to both codes. Initial M3D studies on this problem used a resistive MHD model with a large, empirical perpendicular heat transport value and with modest toroidal resolution (24 toroidal planes). The success of this study prompted the pursuit of more quantitatively accurate predictions by the application of more sophisticated physical models and higher numerical resolution. The results of two consequent follow-up studies are presented here. In the first, the toroidal resolution of the original run is doubled to 48 planes. The behavior of the sawtooth in this case is essentially the same as in the lower- resolution study. The sawtooth study has also been repeated using a two-fluid plasma model, with the effects of the &*circ;i term emphasized. The resulting mode rotation, as well as the effects on the reconnection rate (sawtooth crash time), sawtooth period, and overall stability are presented. [1] W. Park, et al., Phys. Plasmas 6, 1796 (1999). [2] C. Sovinec, et al., J. Comp. Phys. 195, 355 (2004).

Environmental stress induces trinucleotide repeat mutagenesis in human cells

PubMed Central

Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A.; Yotnda, Patricia; Wilson, John H.

2015-01-01

The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)—the cause of multiple human diseases—have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential. PMID:25775519

A Complete and Accurate Ab Initio Repeat Finding Algorithm.

PubMed

Lian, Shuaibin; Chen, Xinwu; Wang, Peng; Zhang, Xiaoli; Dai, Xianhua

2016-03-01

It has become clear that repetitive sequences have played multiple roles in eukaryotic genome evolution including increasing genetic diversity through mutation, changes in gene expression and facilitating generation of novel genes. However, identification of repetitive elements can be difficult in the ab initio manner. Currently, some classical ab initio tools of finding repeats have already presented and compared. The completeness and accuracy of detecting repeats of them are little pool. To this end, we proposed a new ab initio repeat finding tool, named HashRepeatFinder, which is based on hash index and word counting. Furthermore, we assessed the performances of HashRepeatFinder with other two famous tools, such as RepeatScout and Repeatfinder, in human genome data hg19. The results indicated the following three conclusions: (1) The completeness of HashRepeatFinder is the best one among these three compared tools in almost all chromosomes, especially in chr9 (8 times of RepeatScout, 10 times of Repeatfinder); (2) in terms of detecting large repeats, HashRepeatFinder also performed best in all chromosomes, especially in chr3 (24 times of RepeatScout and 250 times of Repeatfinder) and chr19 (12 times of RepeatScout and 60 times of Repeatfinder); (3) in terms of accuracy, HashRepeatFinder can merge the abundant repeats with high accuracy.

Withdrawal of repeated morphine enhances histamine-induced scratching responses in mice.

PubMed

Abe, Kenji; Kobayashi, Kanayo; Yoshino, Saori; Taguchi, Kyoji; Nojima, Hiroshi

2015-04-01

An itch is experientially well known that the scratching response of conditions such as atopic dermatitis is enhanced under psychological stress. Morphine is typical narcotic drug that induces a scratching response upon local application as an adverse drug reaction. Although long-term treatment with morphine will cause tolerance and dependence, morphine withdrawal can cause psychologically and physiologically stressful changes in humans. In this study, we evaluated the effects of morphine withdrawal on histamine-induced scratching behavior in mice. Administration of morphine with progressively increasing doses (10-50 mg/kg, i.p.) was performed for 5 consecutive days. At 3, 24, 48, and 72 hr after spontaneous withdrawal from the final morphine dose, histamine was intradermally injected into the rostral part of the back and then the number of bouts of scratching in 60 min was recorded and summed. We found that at 24 hr after morphine withdrawal there was a significant increase in histamine-induced scratching behavior. The spinal c-Fos positive cells were also significantly increased. The relative adrenal weight increased and the relative thymus weight decreased, both significantly. Moreover, the plasma corticosterone levels changed in parallel with the number of scratching bouts. These results suggest that morphine withdrawal induces a stressed state and enhances in histamine-induced scratching behavior. Increased reaction against histamine in the cervical vertebrae will participate in this stress-induced itch enhancement.

The effect of repeated testing vs repeated practice on skills learning in undergraduate dental education.

PubMed

Sennhenn-Kirchner, S; Goerlich, Y; Kirchner, B; Notbohm, M; Schiekirka, S; Simmenroth, A; Raupach, T

2018-02-01

Recent studies in undergraduate medical education have demonstrated the advantage of repeated testing over repeated practice with regard to knowledge and skills retention. The aim of this study was to investigate whether this "testing effect" also applies to skills retention in undergraduate dental education. In this prospective, randomised controlled trial, fourth-year dental students at Göttingen University Medical Centre participated in a training session on surgical suturing in winter term 2014/2015. Following this, they were either assigned to two sessions of additional skills training (group A) or two sessions of skills assessment with feedback (group B). These sessions were spaced over a period of 4 weeks. Skills retention was assessed in a summative objective structured clinical examination (OSCE) at the end of term, that is 6 months after the initial teaching session. A total of 32 students completed the study. With regard to suturing, OSCE performance was significantly better in group B than group A (81.9±13.1% vs 63.0±15.4%; P=0.001; Cohen's d=1.33). There was no significant OSCE performance difference in the two groups with regard to other learning objectives that were addressed in the end-of-term examination. Thus, the group difference was specific to suturing skills. This is the first study to demonstrate that in dental education, repeated testing produces more favourable skills retention than repeated practice. Test-enhanced learning might be a viable concept for skills retention in undergraduate dentistry education. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Repeated Solid-state Dewetting of Thin Gold Films for Nanogap-rich Plasmonic Nanoislands

PubMed Central

Kang, Minhee; Park, Sang-Gil; Jeong, Ki-Hun

2015-01-01

This work reports a facile wafer-level fabrication for nanogap-rich gold nanoislands for highly sensitive surface enhanced Raman scattering (SERS) by repeating solid-state thermal dewetting of thin gold film. The method provides enlarged gold nanoislands with small gap spacing, which increase the number of electromagnetic hotspots and thus enhance the extinction intensity as well as the tunability for plasmon resonance wavelength. The plasmonic nanoislands from repeated dewetting substantially increase SERS enhancement factor over one order-of-magnitude higher than those from a single-step dewetting process and they allow ultrasensitive SERS detection of a neurotransmitter with extremely low Raman activity. This simple method provides many opportunities for engineering plasmonics for ultrasensitive detection and highly efficient photon collection. PMID:26469768

PH Tester Gauge Repeatability and Reproducibility Study for WO3 Nanostructure Hydrothermal Growth Process

NASA Astrophysics Data System (ADS)

Abd Rashid, Amirul; Hayati Saad, Nor; Bien Chia Sheng, Daniel; Yee, Lee Wai

2014-06-01

PH value is one of the important variables for tungsten trioxide (WO3) nanostructure hydrothermal synthesis process. The morphology of the synthesized nanostructure can be properly controlled by measuring and controlling the pH value of the solution used in this facile synthesis route. Therefore, it is very crucial to ensure the gauge used for pH measurement is reliable in order to achieve the expected result. In this study, gauge repeatability and reproducibility (GR&R) method was used to assess the repeatability and reproducibility of the pH tester. Based on ANOVA method, the design of experimental metrics as well as the result of the experiment was analyzed using Minitab software. It was found that the initial GR&R value for the tester was at 17.55 % which considered as acceptable. To further improve the GR&R level, a new pH measuring procedure was introduced. With the new procedure, the GR&R value was able to be reduced to 2.05%, which means the tester is statistically very ideal to measure the pH of the solution prepared for WO3 hydrothermal synthesis process.

CRISPRcompar: a website to compare clustered regularly interspaced short palindromic repeats.

PubMed

Grissa, Ibtissem; Vergnaud, Gilles; Pourcel, Christine

2008-07-01

Clustered regularly interspaced short palindromic repeat (CRISPR) elements are a particular family of tandem repeats present in prokaryotic genomes, in almost all archaea and in about half of bacteria, and which participate in a mechanism of acquired resistance against phages. They consist in a succession of direct repeats (DR) of 24-47 bp separated by similar sized unique sequences (spacers). In the large majority of cases, the direct repeats are highly conserved, while the number and nature of the spacers are often quite diverse, even among strains of a same species. Furthermore, the acquisition of new units (DR + spacer) was shown to happen almost exclusively on one side of the locus. Therefore, the CRISPR presents an interesting genetic marker for comparative and evolutionary analysis of closely related bacterial strains. CRISPRcompar is a web service created to assist biologists in the CRISPR typing process. Two tools facilitates the in silico investigation: CRISPRcomparison and CRISPRtionary. This website is freely accessible at http://crispr.u-psud.fr/CRISPRcompar/.

Distinct C9orf72-Associated Dipeptide Repeat Structures Correlate with Neuronal Toxicity

PubMed Central

Krans, Amy; Sawaya, Michael R.; Paulson, Henry L.; Todd, Peter K.; Barmada, Sami J.; Ivanova, Magdalena I.

2016-01-01

Hexanucleotide repeat expansions in C9orf72 are the most common inherited cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The expansions elicit toxicity in part through repeat-associated non-AUG (RAN) translation of the intronic (GGGGCC)n sequence into dipeptide repeat-containing proteins (DPRs). Little is known, however, about the structural characteristics and aggregation propensities of the dipeptide units comprising DPRs. To address this question, we synthesized dipeptide units corresponding to the three sense-strand RAN translation products, analyzed their structures by circular dichroism, electron microscopy and dye binding assays, and assessed their relative toxicity when applied to primary cortical neurons. Short, glycine-arginine (GR)3 dipeptides formed spherical aggregates and selectively reduced neuronal survival compared to glycine-alanine (GA)3 and glycine-proline (GP)3 dipeptides. Doubling peptide length had little effect on the structure of GR or GP peptides, but (GA)6 peptides formed β-sheet rich aggregates that bound thioflavin T and Congo red yet lacked the typical fibrillar morphology of amyloids. Aging of (GA)6 dipeptides increased their β-sheet content and enhanced their toxicity when applied to neurons. We also observed that the relative toxicity of each tested dipeptide was proportional to peptide internalization. Our results demonstrate that different C9orf72-related dipeptides exhibit distinct structural properties that correlate with their relative toxicity. PMID:27776165

A Repeat Look at Repeating Patterns

ERIC Educational Resources Information Center

Markworth, Kimberly A.

2016-01-01

A "repeating pattern" is a cyclical repetition of an identifiable core. Children in the primary grades usually begin pattern work with fairly simple patterns, such as AB, ABC, or ABB patterns. The unique letters represent unique elements, whereas the sequence of letters represents the core that is repeated. Based on color, shape,…

Androgen receptor CAG repeat polymorphisms in canine prostate cancer.

PubMed

Lai, C-L; L'Eplattenier, H; van den Ham, R; Verseijden, F; Jagtenberg, A; Mol, J A; Teske, E

2008-01-01

Relatively shorter lengths of the polymorphic polyglutamine repeat-1 of the androgen receptor (AR) have been associated with an increased risk of prostate cancer (PC) in humans. In the dog, there are 2 polymorphic CAG repeat (CAGr) regions. To investigate the relationship of CAGr length of the canine AR-gene and the development of PC. Thirty-two dogs with PC and 172 control dogs were used. DNA was extracted from blood. Both CAG repeats were amplified by polymerase chain reaction (PCR) and PCR products were sequenced. In dogs with PC, CAG-1 repeat length was shorter (P = .001) by an increased proportion of 10 repeats (P = .011) and no 12 repeats (P = .0017) than in the control dogs. No significant changes were found in CAG-3 length distribution. CAG-1 and CAG-3 polymorphisms proved not to be in linkage disequilibrium. Breed difference in allelic distribution was found in the control group. Of the prostate-disease sensitive breeds, a high percentage (64.5%) of the shortest haplotype 10/11 was found in the Doberman, whereas Beagles and German Pointers had higher haplotype 12/11 (47.1 and 50%). Bernese Mountain dogs and Bouvier dogs both shared a high percentage of 11 CAG-1 repeats and 13 CAG-3 repeats. Differences in (combined) allelic distributions among breeds were not significant. In this preliminary study, short CAG-1 repeats in the AR-gene were associated with an increased risk of developing canine PC. Although breed-specific differences in allelic distribution of CAG-1 and CAG-3 repeats were found, these could not be related to PC risk.

DRUGDOG 3.0: U.S. Navy Random Urinalysis Software Package

DTIC Science & Technology

1994-03-15

NAVAL PO11GRADUATE SCHOOL Monterey, California AD-A281 748 THESIS LJuEoTE DRUGDOG 3.0: U. S . NAVY RANDOM URINALYSIS SOFTWARE PACKAGE by (% Dale E...ONLY (Leave blank) 2. REPORT DATE 3. REPORT TYPE AND DATES COVERED 15 MAR 94 Master’s Thesis 4. TITLE AND SUBTITLE DRUGDOG 3.0: U. S . NAVY RANDOM 5...FUNDING NUMBERS URINALYSIS SOFTWARE PACKAGE 6. AUTHOR( S ) Dale E. Wilson 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) 8. PERFORMING Naval

Repeat Radiosurgery for Trigeminal Neuralgia.

PubMed

Helis, Corbin A; Lucas, John T; Bourland, J Daniel; Chan, Michael D; Tatter, Stephen B; Laxton, Adrian W

2015-11-01

Repeat Gamma Knife radiosurgery (GKRS) is an established option for patients whose pain has recurred after the initial procedure, with reported success rates varying from 68% to 95%. Predictive factors for response to the repeat GKRS are ill-defined. This cohort study aimed to report the outcomes and factors predictive of success for patients who have undergone repeated GKRS for trigeminal neuralgia at Wake Forest University Baptist Medical Center. Between 1999 and 2013, 152 patients underwent repeat GKRS at Wake Forest, 125 of whom were available for long-term follow-up. A retrospective chart review and telephone interviews were conducted to determine background medical history, dosimetric data, outcomes, and adverse effects of the procedure. Eighty-four percent of patients achieved at least Barrow Neurological Institute (BNI) IIIb pain relief, with 46% achieving BNI I. The 1-, 3-, and 5-year rates of BNI I pain relief were 63%, 50%, and 37%, respectively. The 1-, 3-, and 5-year rates of BNI IIIb or better pain relief were 74%, 59%, and 46%, respectively. One patient experienced bothersome numbness and 2 patients developed anesthesia dolorosa. The dominant predictive factors for pain relief were facial numbness after the first GKRS and a positive pain response to the first GKRS. Repeat GKRS is an effective method of treating recurrent trigeminal neuralgia. Patients who have facial numbness after the first treatment and a positive pain response to the first GKRS are significantly more likely to respond well to the second treatment.

Hypoxic Repeat Sprint Training Improves Rugby Player's Repeated Sprint but Not Endurance Performance

PubMed Central

Hamlin, Michael J.; Olsen, Peter D.; Marshall, Helen C.; Lizamore, Catherine A.; Elliot, Catherine A.

2017-01-01

This study aims to investigate the performance changes in 19 well-trained male rugby players after repeat-sprint training (six sessions of four sets of 5 × 5 s sprints with 25 s and 5 min of active recovery between reps and sets, respectively) in either normobaric hypoxia (HYP; n = 9; FIO2 = 14.5%) or normobaric normoxia (NORM; n = 10; FIO2 = 20.9%). Three weeks after the intervention, 2 additional repeat-sprint training sessions in hypoxia (FIO2 = 14.5%) was investigated in both groups to gauge the efficacy of using “top-up” sessions for previously hypoxic-trained subjects and whether a small hypoxic dose would be beneficial for the previously normoxic-trained group. Repeated sprint (8 × 20 m) and Yo-Yo Intermittent Recovery Level 1 (YYIR1) performances were tested twice at baseline (Pre 1 and Pre 2) and weekly after (Post 1–3) the initial intervention (intervention 1) and again weekly after the second “top-up” intervention (Post 4–5). After each training set, heart rate, oxygen saturation, and rate of perceived exertion were recorded. Compared to baseline (mean of Pre 1 and Pre 2), both the hypoxic and normoxic groups similarly lowered fatigue over the 8 sprints 1 week after the intervention (Post 1: −1.8 ± 1.6%, −1.5 ± 1.4%, mean change ± 90% CI in HYP and NORM groups, respectively). However, from Post 2 onwards, only the hypoxic group maintained the performance improvement compared to baseline (Post 2: −2.1 ± 1.8%, Post 3: −2.3 ± 1.7%, Post 4: −1.9 ± 1.8%, and Post 5: −1.2 ± 1.7%). Compared to the normoxic group, the hypoxic group was likely to have substantially less fatigue at Post 3–5 (−2.0 ± 2.4%, −2.2 ± 2.4%, −1.6 ± 2.4% Post 3, Post 4, Post 5, respectively). YYIR1 performances improved throughout the recovery period in both groups (13–37% compared to baseline) with unclear differences found between groups. The addition of two sessions of “top-up” training after intervention 1, had little effect on either

The effectiveness of repeat lumbar transforaminal epidural steroid injections.

PubMed

Murthy, Naveen S; Geske, Jennifer R; Shelerud, Randy A; Wald, John T; Diehn, Felix E; Thielen, Kent R; Kaufmann, Timothy J; Morris, Jonathan M; Lehman, Vance T; Amrami, Kimberly K; Carter, Rickey E; Maus, Timothy P

2014-10-01

The aim of this study was to determine 1) if repeat lumbar transforaminal epidural steroid injections (TFESIs) resulted in recovery of pain relief, which has waned since an index injection, and 2) if cumulative benefit could be achieved by repeat injections within 3 months of the index injection. Retrospective observational study with statistical modeling of the response to repeat TFESI. Academic radiology practice. Two thousand eighty-seven single-level TFESIs were performed for radicular pain on 933 subjects. Subjects received repeat TFESIs >2 weeks and <1 year from the index injection. Hierarchical linear modeling was performed to evaluate changes in continuous and categorical pain relief outcomes after repeat TFESI. Subgroup analyses were performed on patients with <3 months duration of pain (acute pain), patients receiving repeat injections within 3 months (clustered injections), and in patients with both acute pain and clustered injections. Repeat TFESIs achieved pain relief in both continuous and categorical outcomes. Relative to the index injection, there was a minimal but statistically significant decrease in pain relief in modeled continuous outcome measures with subsequent injections. Acute pain patients recovered all prior benefit with a statistically significant cumulative benefit. Patients receiving clustered injections achieved statistically significant cumulative benefit, of greater magnitude in acute pain patients. Repeat TFESI may be performed for recurrence of radicular pain with the expectation of recovery of most or all previously achieved benefit; acute pain patients will likely recover all prior benefit. Repeat TFESIs within 3 months of the index injection can provide cumulative benefit. Wiley Periodicals, Inc.

Assessment of long-term outcomes associated with urinary prostate cancer antigen 3 and TMPRSS2:ERG gene fusion at repeat biopsy.

PubMed

Merdan, Selin; Tomlins, Scott A; Barnett, Christine L; Morgan, Todd M; Montie, James E; Wei, John T; Denton, Brian T

2015-11-15

In men with clinically localized prostate cancer who have undergone at least 1 previous negative biopsy and have elevated serum prostate-specific antigen (PSA) levels, long-term health outcomes associated with the assessment of urinary prostate cancer antigen 3 (PCA3) and the transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene fusion (T2:ERG) have not been investigated previously in relation to the decision to recommend a repeat biopsy. The authors performed a decision analysis using a decision tree for men with elevated PSA levels. The probability of cancer was estimated using the Prostate Cancer Prevention Trial Risk Calculator (version 2.0). The use of PSA alone was compared with the use of PCA3 and T2:ERG scores, with each evaluated independently, in combination with PSA to trigger a repeat biopsy. When PCA3 and T2:ERG score evaluations were used, predefined thresholds were established to determine whether the patient should undergo a repeat biopsy. Biopsy outcomes were defined as either positive (with a Gleason score of <7, 7, or >7) or negative. Probabilities and estimates of 10-year overall survival and 15-year cancer-specific survival were derived from previous studies and a literature review. Outcomes were defined as age-dependent and Gleason score-dependent 10-year overall and 15-year cancer-specific survival rates and the percentage of biopsies avoided. Incorporating the PCA3 score (biopsy threshold, 25; generated based on the urine PCA3 level normalized to the amount of PSA messenger RNA) or the T2:ERG score (biopsy threshold, 10; based on the urine T2:ERG level normalized to the amount of PSA messenger RNA) into the decision to recommend repeat biopsy would have avoided 55.4% or 64.7% of repeat biopsies for the base-case patient, respectively, and changes in the 10-year survival rate were only 0.93% or 1.41%, respectively. Multi-way sensitivity analyses suggested that these results were robust

Rescue of cardiomyopathy through U7snRNA-mediated exon skipping in Mybpc3-targeted knock-in mice.

PubMed

Gedicke-Hornung, Christina; Behrens-Gawlik, Verena; Reischmann, Silke; Geertz, Birgit; Stimpel, Doreen; Weinberger, Florian; Schlossarek, Saskia; Précigout, Guillaume; Braren, Ingke; Eschenhagen, Thomas; Mearini, Giulia; Lorain, Stéphanie; Voit, Thomas; Dreyfus, Patrick A; Garcia, Luis; Carrier, Lucie

2013-07-01

Exon skipping mediated by antisense oligoribonucleotides (AON) is a promising therapeutic approach for genetic disorders, but has not yet been evaluated for cardiac diseases. We investigated the feasibility and efficacy of viral-mediated AON transfer in a Mybpc3-targeted knock-in (KI) mouse model of hypertrophic cardiomyopathy (HCM). KI mice carry a homozygous G>A transition in exon 6, which results in three different aberrant mRNAs. We identified an alternative variant (Var-4) deleted of exons 5-6 in wild-type and KI mice. To enhance its expression and suppress aberrant mRNAs we designed AON-5 and AON-6 that mask splicing enhancer motifs in exons 5 and 6. AONs were inserted into modified U7 small nuclear RNA and packaged in adeno-associated virus (AAV-U7-AON-5+6). Transduction of cardiac myocytes or systemic administration of AAV-U7-AON-5+6 increased Var-4 mRNA/protein levels and reduced aberrant mRNAs. Injection of newborn KI mice abolished cardiac dysfunction and prevented left ventricular hypertrophy. Although the therapeutic effect was transient and therefore requires optimization to be maintained over an extended period, this proof-of-concept study paves the way towards a causal therapy of HCM. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase-dependent DNA repair

PubMed Central

Nowarski, Roni; Wilner, Ofer I.; Cheshin, Ori; Shahar, Or D.; Kenig, Edan; Baraz, Leah; Britan-Rosich, Elena; Nagler, Arnon; Harris, Reuben S.; Goldberg, Michal; Willner, Itamar

2012-01-01

APOBEC3 proteins catalyze deamination of cytidines in single-stranded DNA (ssDNA), providing innate protection against retroviral replication by inducing deleterious dC > dU hypermutation of replication intermediates. APOBEC3G expression is induced in mitogen-activated lymphocytes; however, no physiologic role related to lymphoid cell proliferation has yet to be determined. Moreover, whether APOBEC3G cytidine deaminase activity transcends to processing cellular genomic DNA is unknown. Here we show that lymphoma cells expressing high APOBEC3G levels display efficient repair of genomic DNA double-strand breaks (DSBs) induced by ionizing radiation and enhanced survival of irradiated cells. APOBEC3G transiently accumulated in the nucleus in response to ionizing radiation and was recruited to DSB repair foci. Consistent with a direct role in DSB repair, inhibition of APOBEC3G expression or deaminase activity resulted in deficient DSB repair, whereas reconstitution of APOBEC3G expression in leukemia cells enhanced DSB repair. APOBEC3G activity involved processing of DNA flanking a DSB in an integrated reporter cassette. Atomic force microscopy indicated that APOBEC3G multimers associate with ssDNA termini, triggering multimer disassembly to multiple catalytic units. These results identify APOBEC3G as a prosurvival factor in lymphoma cells, marking APOBEC3G as a potential target for sensitizing lymphoma to radiation therapy. PMID:22645179

APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase-dependent DNA repair.

PubMed

Nowarski, Roni; Wilner, Ofer I; Cheshin, Ori; Shahar, Or D; Kenig, Edan; Baraz, Leah; Britan-Rosich, Elena; Nagler, Arnon; Harris, Reuben S; Goldberg, Michal; Willner, Itamar; Kotler, Moshe

2012-07-12

APOBEC3 proteins catalyze deamination of cytidines in single-stranded DNA (ssDNA), providing innate protection against retroviral replication by inducing deleterious dC > dU hypermutation of replication intermediates. APOBEC3G expression is induced in mitogen-activated lymphocytes; however, no physiologic role related to lymphoid cell proliferation has yet to be determined. Moreover, whether APOBEC3G cytidine deaminase activity transcends to processing cellular genomic DNA is unknown. Here we show that lymphoma cells expressing high APOBEC3G levels display efficient repair of genomic DNA double-strand breaks (DSBs) induced by ionizing radiation and enhanced survival of irradiated cells. APOBEC3G transiently accumulated in the nucleus in response to ionizing radiation and was recruited to DSB repair foci. Consistent with a direct role in DSB repair, inhibition of APOBEC3G expression or deaminase activity resulted in deficient DSB repair, whereas reconstitution of APOBEC3G expression in leukemia cells enhanced DSB repair. APOBEC3G activity involved processing of DNA flanking a DSB in an integrated reporter cassette. Atomic force microscopy indicated that APOBEC3G multimers associate with ssDNA termini, triggering multimer disassembly to multiple catalytic units. These results identify APOBEC3G as a prosurvival factor in lymphoma cells, marking APOBEC3G as a potential target for sensitizing lymphoma to radiation therapy.

Opposing Control by Transcription Factors MYB61 and MYB3 Increases Freezing Tolerance by Relieving C-Repeat Binding Factor Suppression1[OPEN

PubMed Central

Zhang, Yunqin; Miao, Zhenyan; Xie, Can; Meng, Xiangzhao; Deng, Jie; Mysore, Kirankumar S.; Frugier, Florian; Wang, Tao

2016-01-01

Cold acclimation is an important process by which plants respond to low temperature and enhance their winter hardiness. C-REPEAT BINDING FACTOR1 (CBF1), CBF2, and CBF3 genes were shown previously to participate in cold acclimation in Medicago truncatula. In addition, MtCBF4 is transcriptionally induced by salt, drought, and cold stresses. We show here that MtCBF4, shown previously to enhance drought and salt tolerance, also positively regulates cold acclimation and freezing tolerance. To identify molecular factors acting upstream and downstream of the MtCBF4 transcription factor (TF) in cold responses, we first identified genes that are differentially regulated upon MtCBF4 overexpression using RNAseq Digital Gene Expression Profiling. Among these, we showed that MtCBF4 directly activates the transcription of the COLD ACCLIMATION SPECIFIC15 (MtCAS15) gene. To gain insights into how MtCBF4 is transcriptionally regulated in response to cold, an R2R3-MYB TF, MtMYB3, was identified based on a yeast one-hybrid screen as binding directly to MYB cis-elements in the MtCBF4 promoter, leading to the inhibition of MtCBF4 expression. In addition, another MYB TF, MtMYB61, identified as an interactor of MtMYB3, can relieve the inhibitory effect of MtMYB3 on MtCBF4 transcription. This study, therefore, supports a model describing how MtCBF4 is regulated by antagonistic MtMYB3/MtMYB61 TFs, leading to the up-regulation of downstream targets such as MtCAS15 acting in cold acclimation in M. truncatula. PMID:27578551

Disease-associated repeat instability and mismatch repair.

PubMed

Schmidt, Monika H M; Pearson, Christopher E

2016-02-01

Expanded tandem repeat sequences in DNA are associated with at least 40 human genetic neurological, neurodegenerative, and neuromuscular diseases. Repeat expansion can occur during parent-to-offspring transmission, and arise at variable rates in specific tissues throughout the life of an affected individual. Since the ongoing somatic repeat expansions can affect disease age-of-onset, severity, and progression, targeting somatic expansion holds potential as a therapeutic target. Thus, understanding the factors that regulate this mutation is crucial. DNA repair, in particular mismatch repair (MMR), is the major driving force of disease-associated repeat expansions. In contrast to its anti-mutagenic roles, mammalian MMR curiously drives the expansion mutations of disease-associated (CAG)·(CTG) repeats. Recent advances have broadened our knowledge of both the MMR proteins involved in disease repeat expansions, including: MSH2, MSH3, MSH6, MLH1, PMS2, and MLH3, as well as the types of repeats affected by MMR, now including: (CAG)·(CTG), (CGG)·(CCG), and (GAA)·(TTC) repeats. Mutagenic slipped-DNA structures have been detected in patient tissues, and the size of the slip-out and their junction conformation can determine the involvement of MMR. Furthermore, the formation of other unusual DNA and R-loop structures is proposed to play a key role in MMR-mediated instability. A complex correlation is emerging between tissues showing varying amounts of repeat instability and MMR expression levels. Notably, naturally occurring polymorphic variants of DNA repair genes can have dramatic effects upon the levels of repeat instability, which may explain the variation in disease age-of-onset, progression and severity. An increasing grasp of these factors holds prognostic and therapeutic potential. Copyright © 2015 Elsevier B.V. All rights reserved.

Global SO(3) x SO(3) x U(1) symmetry of the Hubbard model on bipartite lattices

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

Carmelo, J.M.P., E-mail: carmelo@fisica.uminho.p; Ostlund, Stellan; Sampaio, M.J.

2010-08-15

In this paper the global symmetry of the Hubbard model on a bipartite lattice is found to be larger than SO(4). The model is one of the most studied many-particle quantum problems, yet except in one dimension it has no exact solution, so that there remain many open questions about its properties. Symmetry plays an important role in physics and often can be used to extract useful information on unsolved non-perturbative quantum problems. Specifically, here it is found that for on-site interaction U {ne} 0 the local SU(2) x SU(2) x U(1) gauge symmetry of the Hubbard model on amore » bipartite lattice with N{sub a}{sup D} sites and vanishing transfer integral t = 0 can be lifted to a global [SU(2) x SU(2) x U(1)]/Z{sub 2}{sup 2} = SO(3) x SO(3) x U(1) symmetry in the presence of the kinetic-energy hopping term of the Hamiltonian with t > 0. (Examples of a bipartite lattice are the D-dimensional cubic lattices of lattice constant a and edge length L = N{sub a}a for which D = 1, 2, 3,... in the number N{sub a}{sup D} of sites.) The generator of the new found hidden independent charge global U(1) symmetry, which is not related to the ordinary U(1) gauge subgroup of electromagnetism, is one half the rotated-electron number of singly occupied sites operator. Although addition of chemical-potential and magnetic-field operator terms to the model Hamiltonian lowers its symmetry, such terms commute with it. Therefore, its 4{sup N}{sub a}{sup D} energy eigenstates refer to representations of the new found global [SU(2) x SU(2) x U(1)]/Z{sub 2}{sup 2} = SO(3) x SO(3) x U(1) symmetry. Consistently, we find that for the Hubbard model on a bipartite lattice the number of independent representations of the group SO(3) x SO(3) x U(1) equals the Hilbert-space dimension 4{sup N}{sub a}{sup D}. It is confirmed elsewhere that the new found symmetry has important physical consequences.« less

Tank 241-U-103, grab samples 3U-99-1, 3u-99-2 and 3U-99-3

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

STEEN, F.H.

This document is the final report for tank 241-U-103 grab samples. Three grab samples were collected from riser 13 on March 12, 1999 and received by the 222-S laboratory on March 15, 1999. Analyses were performed in accordance with the Compatibility Grab Sampling and Analysis Plan for Fiscal year 1999 (TSAP) and the Data Quality Objectives for Tank Farms Waste Compatibility Program (DQO). The analytical results are presented in the data summary report. None of the subsamples submitted for differential scanning calorimetry (DSC), total organic carbon (TOC) and plutonium 239 (Pu239) analyses exceeded the notification limits as stated in TSAP.

De-phosphorylation of TR{alpha}-1 by p44/42 MAPK inhibition enhances T{sub 3}-mediated GLUT5 gene expression in the intestinal cell line Caco-2 cells

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

Mochizuki, Kazuki; Sakaguchi, Naomi; Takabe, Satsuki

2007-08-10

Thyroid hormone and p44/42 MAPK inactivation are important in intestinal differentiation. We demonstrated not only that treatment with p44/42 MAPK inhibitor U0126 in intestinal cell line Caco-2 cells reduced the phosphorylation of serine and threonine residues of TR{alpha}-1, but also that T{sub 3} and U0126 synergistically induced GLUT5 gene expression. EMSA demonstrated that the binding activity of TR{alpha}-1-RXR heterodimer on GLUT5-TRE in nuclear proteins of Caco-2 cells was synergistically enhanced by co-incubation in vitro with T{sub 3} and CIAP, which strongly de-phosphorylates proteins. ChIP and transfection assays revealed that co-treatment of T{sub 3} and U0126 induces TR{alpha}-1-RXR binding to GLUT5-TREmore » on the human GLUT5 enhancer region, and recruitment of the transcriptional complex in cells. These results suggest that inactivation of p44/42 MAPK enhances T{sub 3}-induced GLUT5 gene expression in Caco-2 cells through increasing TR{alpha}-1 transactivity and binding activity to the GLUT5-TRE, probably due to de-phosphorylation of TR{alpha}-1.« less

Evolutionary conservation of sequence and secondary structures inCRISPR repeats

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

Kunin, Victor; Sorek, Rotem; Hugenholtz, Philip

Clustered Regularly Interspaced Palindromic Repeats (CRISPRs) are a novel class of direct repeats, separated by unique spacer sequences of similar length, that are present in {approx}40% of bacterial and all archaeal genomes analyzed to date. More than 40 gene families, called CRISPR-associated sequences (CAS), appear in conjunction with these repeats and are thought to be involved in the propagation and functioning of CRISPRs. It has been proposed that the CRISPR/CAS system samples, maintains a record of, and inactivates invasive DNA that the cell has encountered, and therefore constitutes a prokaryotic analog of an immune system. Here we analyze CRISPR repeatsmore » identified in 195 microbial genomes and show that they can be organized into multiple clusters based on sequence similarity. All individual repeats in any given cluster were inferred to form characteristic RNA secondary structure, ranging from non-existent to pronounced. Stable secondary structures included G:U base pairs and exhibited multiple compensatory base changes in the stem region, indicating evolutionary conservation and functional importance. We also show that the repeat-based classification corresponds to, and expands upon, a previously reported CAS gene-based classification including specific relationships between CRISPR and CAS subtypes.« less

Repeatability of short-duration transient visual evoked potentials in normal subjects.

PubMed

Tello, Celso; De Moraes, Carlos Gustavo V; Prata, Tiago S; Derr, Peter; Patel, Jayson; Siegfried, John; Liebmann, Jeffrey M; Ritch, Robert

2010-06-01

To evaluate the within-session and inter-session repeatability of a new, short-duration transient visual evoked potential (SD-tVEP) device on normal individuals, we tested 30 normal subjects (20/20 visual acuity, normal 24-2 SITA Standard VF) with SD-tVEP. Ten of these subjects had their tests repeated within 1-2 months from the initial visit. Synchronized single-channel EEG was recorded using a modified Diopsys Enfant System (Diopsys, Inc., Pine Brook, New Jersey, USA). A checkerboard stimulus was modulated at two reversals per second. Two different contrasts of checkerboard reversal patterns were used: 85% Michelson contrast with a mean luminance of 66.25 cd/m(2) and 10% Michelson contrast with a mean luminance of 112 cd/m(2). Each test lasted 20 s. Both eyes, independently and together, were tested 10 times (5 times at each contrast level). The following information was identified from the filtered N75-P100-N135 complex: N75 amplitude, N75 latency, P100 amplitude, P100 latency, and Delta Amplitude (N75-P100). The median values for each eye's five SD-tVEP parameters were calculated and grouped into two data sets based on contrast level. Mean age was 27.3 +/- 5.2 years. For OD only, the median (95% confidence intervals) of Delta Amplitude (N75-P100) amplitudes at 10% and 85% contrast were 4.6 uV (4.1-5.9) and 7.1 uV (5.15-9.31). The median P100 latencies were 115.2 ms (112.0-117.7) and 104.0 ms (99.9-106.0). There was little within-session variability for any of these parameters. Intraclass correlation coefficients ranged between 0.64 and 0.98, and within subject coefficients of variation were 3-5% (P100 latency) and 15-30% (Delta Amplitude (N75-P100) amplitude). Bland-Altman plots showed good agreement between the first and fifth test sessions (85% contrast Delta Amplitude (N75-P100) delta amplitude, mean difference, 0.48 mV, 95% CI, -0.18-1.12; 85% contrast P100 latency delay, -0.82 ms, 95% CI, -3.12-1.46; 10% contrast Delta Amplitude (N75-P100) amplitude, 0

Screened Hybrid and DFT + U Studies of the Structural, Electronic, and Optical Properties of U3O8

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

Wen, Xiaodong; Martin, Richard L.; Scuseria, Gustavo E.

2012-11-26

A systematic comparison of the structures and electronic and optical properties of U3O8 in the c2mm, P¯62m, and P21/m structures (the α, β, and γ phases, respectively) is performed using density functional theory + U (PBE + U) and the Heyd–Scuseria–Ernzerhof screened hybrid functional (HSE). The relationship between the semiconducting C2mm phase of U3O8 and the high temperature, metallic P¯62m phase is explored in more detail. Our calculated results show that the HSE functional gives a better description of the electronic and optical properties when compared with available experimental data for the α and β phases, but neither approach doesmore » particularly well for the high pressure γ phase.« less

Mass enhancement versus Stoner enhancement in strongly correlated metallic perovskites: LaNiO3 and LaCuO3

NASA Astrophysics Data System (ADS)

Zhou, J.-S.; Marshall, L. G.; Goodenough, J. B.

2014-06-01

Measurements of physical properties, including transport and magnetic properties, specific heat, and thermal conductivity, have been performed on high-quality samples of LaNiO3 and LaCuO3 synthesized under high pressure. Some measurements, such as thermoelectric power and magnetic susceptibility, have been made under high pressure. The availability of a complete set of data enables a side-by-side comparison between these two narrowband systems. We have demonstrated unambiguously the mass enhancement due to electron-electron correlations in both systems relative to the recent density functional theory results. Correlations in these narrowband systems also enhance the magnetic susceptibility. Ferromagnetic spin fluctuations give rise to a strong Stoner enhancement in the magnetic susceptibility in the quarter-filled LaNiO3. Although we are able to tune the bandwidth by either chemical substitutions or by applying hydrostatic pressure on LaNiO3, the Stoner enhancement does not lead to the Stoner instability.

The Desert Laboratory Repeat Photography Collection - An Invaluable Archive Documenting Landscape Change

USGS Publications Warehouse

Webb, Robert H.; Boyer, Diane E.; Turner, Raymond M.; Bullock, Stephen H.

2007-01-01

The Desert Laboratory Repeat Photography Collection, the largest collection of its kind in the world, is housed at the U.S. Geological Survey (USGS) in Tucson, Arizona. The collection preserves thousands of photos taken precisely in the same places but at different times. This archive of 'repeat photographs' documents changes in the desert landscape and vegetation of the American Southwest, and also includes images from northwestern Mexico and Kenya. These images are an invaluable asset to help understand the effects of climate variation and land-use practices on arid and semiarid environments.

A Gammaherpesviral Internal Repeat Contributes to Latency Amplification

PubMed Central

Thakur, Nagendra N.; El-Gogo, Susanne; Steer, Beatrix; Freimüller, Klaus; Waha, Andreas; Adler, Heiko

2007-01-01

Background Gammaherpesviruses cause important infections of humans, in particular in immunocompromised patients. The genomes of gammaherpesviruses contain variable numbers of internal repeats whose precise role for in vivo pathogenesis is not well understood. Methodology/Principal Findings We used infection of laboratory mice with murine gammaherpesvirus 68 (MHV-68) to explore the biological role of the 40 bp internal repeat of MHV-68. We constructed several mutant viruses partially or completely lacking this repeat. Both in vitro and in vivo, the loss of the repeat did not substantially affect lytic replication of the mutant viruses. However, the extent of splenomegaly, which is associated with the establishment of latency, and the number of ex vivo reactivating and genome positive splenocytes were reduced. Since the 40 bp repeat is part of the hypothetical open reading frame (ORF) M6, it might function as part of M6 or as an independent structure. To differentiate between these two possibilities, we constructed an N-terminal M6STOP mutant, leaving the repeat structure intact but rendering ORF M6 unfunctional. Disruption of ORF M6 did neither affect lytic nor latent infection. In contrast to the situation in lytically infected NIH3T3 cells, the expression of the latency-associated genes K3 and ORF72 was reduced in the latently infected murine B cell line Ag8 in the absence of the 40 bp repeat. Conclusions/Significance These data suggest that the 40 bp repeat contributes to latency amplification and might be involved in the regulation of viral gene expression. PMID:17710133

1.688 g/cm(3) satellite-related repeats: a missing link to dosage compensation and speciation.

PubMed

Gallach, Miguel

2015-09-01

Despite the important progress that has been made on dosage compensation (DC), a critical link in our understanding of the X chromosome recognition mechanisms is still missing. Recent studies in Drosophila indicate that the missing link could be a family of DNA repeats populating the euchromatin of the X chromosome. In this opinion article, I discuss how these findings add a new fresh twist on the DC problem. In the following sections, I first summarize our understanding of DC in Drosophila and integrate these recent discoveries into our knowledge of the X chromosome recognition problem. Next, I introduce a model according to which, 1.688 g/cm(3) satellite-related (SR) repeats would be the primary recognition elements for the dosage compensation complex. Contrary to the current belief, I suggest that the DC system in Drosophila is not conserved and static, but it is continuously co-evolving with the target SR repeats. The potential role of the SR repeats in hybrid incompatibilities and speciation is also discussed. © 2015 John Wiley & Sons Ltd.

Purα Repaired Expanded Hexanucleotide GGGGCC Repeat Noncoding RNA-Caused Neuronal Toxicity in Neuro-2a Cells.

PubMed

Shen, Jianying; Zhang, Yu; Zhao, Shi; Mao, Hong; Wang, Zhongjing; Li, Honglian; Xu, Zihui

2018-05-01

Expanded hexanucleotide GGGGCC repeat in a noncoding region of C9ORF72 is the most common cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). However, its molecular pathogenesis remains unclear. In our previous study, the expanded GGGGCC repeats have been shown to be sufficient to cause neurodegeneration. In order to investigate the further role of expanded GGGGCC repeats in the neuron, the normal r(GGGGCC) 3 and mutant-type expanded r(GGGGCC) 30 expression vectors were transfected into Neuro-2a cells. Cell proliferation, dendrite development, and the proteins' levels of microtubule-associated protein-2 (MAP2) and cyclin-dependent kinase-5 (CDK5) were used to evaluate the cell toxicity of GGGGCC repeats on Neuro-2a cells. The results were shown that expression of expanded GGGGCC repeats caused neuronal cell toxicity in Neuro-2a cells, enhanced the expression of pMAP2 and pCDK5. Moreover, overexpression of Purα repaired expanded GGGGCC repeat-inducing neuronal toxicity in Neuro-2a cells and reduced the expression of pMAP2 and pCDK5. In all, our findings suggested that the expanded GGGGCC repeats might cause neurodegeneration through destroyed neuron cells. And the GGGGCC repeat-induced neuronal cell toxicity was inhibited by upregulation of Purα. We inferred that Purα inhibits expanded GGGGCC repeat-inducing neurodegeneration, which might reveal a novel mechanism of neurodegenerative diseases ALS and FTD.

Thermophysical properties of U 3 Si 2 to 1773K

DOE PAGES

White, Joshua Taylor; Nelson, Andrew Thomas; Dunwoody, John Tyler; ...

2015-05-08

Use of U 3Si 2 in nuclear reactors requires accurate thermophysical property data to capture heat transfer within the core. Compilation of the limited previous research efforts focused on the most critical property, thermal conductivity, reveals extensive disagreement. Assessment of this data is challenged by the fact that the critical structural and chemical details of the material used to provide historic data is either absent or confirms the presence of significant impurity phases. This study was initiated to fabricate high purity U 3Si 2 to quantify the coefficient of thermal expansion, heat capacity, thermal diffusivity, and thermal conductivity from roommore » temperature to 1773 K. Here, the datasets provided in this manuscript will facilitate more detailed fuel performance modeling to assess both current and proposed reactor designs that incorporate U 3Si 2.« less

3 CFR 8796 - Proclamation 8796 of April 3, 2012. Education and Sharing Day, U.S.A., 2012

Code of Federal Regulations, 2013 CFR

2013-01-01

... 3 The President 1 2013-01-01 2013-01-01 false Proclamation 8796 of April 3, 2012. Education and Sharing Day, U.S.A., 2012 8796 Proclamation 8796 Presidential Documents Proclamations Proclamation 8796 of April 3, 2012 Proc. 8796 Education and Sharing Day, U.S.A., 2012By the President of the United States of...

Transportation assimilation revisited: New evidence from repeated cross-sectional survey data

PubMed Central

2018-01-01

Background Based on single cross-sectional data, prior research finds evidence of “transportation assimilation” among U.S. immigrants: the length of stay in the U.S. is negatively correlated with public transit use. This paper revisits this question by using repeated cross-sectional data, and examines the trend of transportation assimilation over time. Methods and results Using 1980, 1990, 2000 1% census and 2010 (1%) American Community Survey, I examine the relationship between the length of stay in the U.S. and public transit ridership among immigrants. I first run regressions separately in four data sets: I regress public transit ridership on the length of stay, controlling for other individual and geographic variables. I then compare the magnitudes of the relationship in four regressions. To study how the rate of transportation assimilation changes over time, I pool the data set and regress public transit ridership on the length of stay and its interactions with year dummies to compare the coefficients across surveys. Results confirm the conclusion of transportation assimilation: as the length of stay in the U.S. increases, an immigrant’s public transit use decreases. However, the repeated cross-section analysis suggests the assimilation rate has been decreasing in the past few decades. Conclusions This paper finds evidence of transportation assimilation: immigrants become less likely to ride public transit as the length of stay in the U.S. increases. The assimilation rate, however, has been decreasing over time. This paper finds that the rate of public transit ridership among new immigrants upon arrival, the geographic distribution of immigrants, and the changing demographics of the U.S. immigrants play roles in affecting the trend of transportation assimilation. PMID:29668676

Enhancement of cutaneous wound healing by Dsg2 augmentation of uPAR secretion.

PubMed

Cooper, Felicia; Overmiller, Andrew M; Loder, Anthony; Brennan-Crispi, Donna M; McGuinn, Kathleen P; Marous, Molly R; Freeman, Theresa A; Riobo-Del Galdo, Natalia A; Siracusa, Linda D; Wahl, James K; Mahoney, Mỹ G

2018-05-09

In addition to playing a role in adhesion, desmoglein 2 (Dsg2) is an important regulator of growth and survival signaling pathways, cell proliferation, migration and invasion, and oncogenesis. While low-level Dsg2 expression is observed in basal keratinocytes and is downregulated in non-healing venous ulcers, overexpression has been observed in both melanomas and non-melanoma malignancies. Here, we show that transgenic mice overexpressing Dsg2 in basal keratinocytes primed the activation of mitogenic pathways, but did not induce dramatic epidermal changes or susceptibility to chemical-induced tumor development. Interestingly, acceleration of full-thickness wound closure and increased wound-adjacent keratinocyte proliferation was observed in these mice. As epidermal cytokines and their receptors play critical roles in wound healing, Dsg2-induced secretome alterations were assessed with an antibody profiler array and revealed increased release and proteolytic processing of the urokinase-type plasminogen activator receptor (uPAR). Dsg2 induced uPAR expression in the skin of transgenic compared to wild-type mice. Wound healing further enhanced uPAR in both epidermis and dermis with concomitant increase in the pro-healing laminin-332, a major component of the basement membrane zone, in transgenic mice. This study demonstrates that Dsg2 induces epidermal activation of various signaling cascades and accelerates cutaneous wound healing, in part, through uPAR-related signaling cascades. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The RhoU/Wrch1 Rho GTPase gene is a common transcriptional target of both the gp130/STAT3 and Wnt-1 pathways

PubMed Central

SCHIAVONE, Davide; DEWILDE, Sarah; VALLANIA, Francesco; TURKSON, James; CUNTO, Ferdinando DI; POLI, Valeria

2010-01-01

STAT3 (signal transducer and activator of transcription 3) is a transcription factor activated by cytokines, growth factors and oncogenes, whose activity is required for cell survival/proliferation of a wide variety of primary tumours and tumour cell lines. Prominent among its multiple effects on tumour cells is the stimulation of cell migration and metastasis, whose functional mechanisms are however not completely characterized. RhoU/Wrch1 (Wnt-responsive Cdc42 homologue) is an atypical Rho GTPase thought to be constitutively bound to GTP. RhoU was first identified as a Wnt-1-inducible mRNA and subsequently shown to act on the actin cytoskeleton by stimulating filopodia formation and stress fibre dissolution. It was in addition recently shown to localize to focal adhesions and to Src-induced podosomes and enhance cell migration. RhoU overexpression in mammary epithelial cells stimulates quiescent cells to re-enter the cell cycle and morphologically phenocopies Wnt-1-dependent transformation. In the present study we show that Wnt-1-mediated RhoU induction occurs at the transcriptional level. Moreover, we demonstrate that RhoU can also be induced by gp130 cytokines via STAT3, and we identify two functional STAT3-binding sites on the mouse RhoU promoter. RhoU induction by Wnt-1 is independent of β-catenin, but does not involve STAT3. Rather, it is mediated by the Wnt/planar cell polarity pathway through the activation of JNK (c-Jun N-terminal kinase). Both the so-called non-canonical Wnt pathway and STAT3 are therefore able to induce RhoU, which in turn may be involved in mediating their effects on cell migration. PMID:19397496

Enhanced capture rate for haze defects in production wafer inspection

NASA Astrophysics Data System (ADS)

Auerbach, Ditza; Shulman, Adi; Rozentsvige, Moshe

2010-03-01

involved scanning with three different recipe types: Standard Inspection: Nominal recipe with a low false alarm rate was used to scan the wafer and repeaters were extracted from the final defect map. Haze Monitoring Application: Recipe sensitivity was enhanced and run on a single field column from which on repeating defects were extracted. Enhanced Repeater Extractor: Defect processing included the two parallel routes: a nominal recipe for the random defects and the new high sensitive repeater extractor algorithm. The results showed that the new application (recipe #3) had the highest capture rate on haze defects and detected new repeater defects not found in the first two recipes. In addition, the recipe was much simpler to setup since repeaters are filtered separately from random defects. We expect that in the future, with the advent of mask-less lithography and EUV lithography, the monitoring of field and die repeating defects on the wafer will become a necessity for process control in the semiconductor fab.

Manipulating multiple order parameters via oxygen vacancies: The case of E u0.5B a0.5Ti O3 -δ

NASA Astrophysics Data System (ADS)

Li, Weiwei; He, Qian; Wang, Le; Zeng, Huizhong; Bowlan, John; Ling, Langsheng; Yarotski, Dmitry A.; Zhang, Wenrui; Zhao, Run; Dai, Jiahong; Gu, Junxing; Shen, Shipeng; Guo, Haizhong; Pi, Li; Wang, Haiyan; Wang, Yongqiang; Velasco-Davalos, Ivan A.; Wu, Yangjiang; Hu, Zhijun; Chen, Bin; Li, Run-Wei; Sun, Young; Jin, Kuijuan; Zhang, Yuheng; Chen, Hou-Tong; Ju, Sheng; Ruediger, Andreas; Shi, Daning; Borisevich, Albina Y.; Yang, Hao

2017-09-01

Controlling functionalities, such as magnetism or ferroelectricity, by means of oxygen vacancies (VO) is a key issue for the future development of transition-metal oxides. Progress in this field is currently addressed through VO variations and their impact on mainly one order parameter. Here we reveal a mechanism for tuning both magnetism and ferroelectricity simultaneously by using VO. Combining experimental and density-functional theory studies of E u0.5B a0.5Ti O3 -δ , we demonstrate that oxygen vacancies create T i3 +3 d1 defect states, mediating the ferromagnetic coupling between the localized Eu 4 f7 spins, and increase an off-center displacement of Ti ions, enhancing the ferroelectric Curie temperature. The dual function of Ti sites also promises a magnetoelectric coupling in the E u0.5B a0.5Ti O3 -δ .

Optimal gadolinium dose level for magnetic resonance imaging (MRI) contrast enhancement of U87-derived tumors in athymic nude rats for the assessment of photodynamic therapy

NASA Astrophysics Data System (ADS)

Cross, Nathan; Varghai, Davood; Flask, Chris A.; Feyes, Denise K.; Oleinick, Nancy L.; Dean, David

2009-02-01

This study aims to determine the effect of varying gadopentetate dimeglumine (Gd-DTPA) dose on Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) tracking of brain tumor photodynamic therapy (PDT) outcome. Methods: We injected 2.5 x 105 U87 cells (derived from human malignant glioma) into the brains of six athymic nude rats. After 9, 12, and 13 days DCE-MRI images were acquired on a 9.4 T micro-MRI scanner before and after administration of 100, 150, or 200 μL of Gd-DTPA. Results: Tumor region normalized DCE-MRI scan enhancement at peak was: 1.217 over baseline (0.018 Standard Error [SE]) at the 100 μL dose, 1.339 (0.013 SE) at the 150 μL dose, and 1.287 (0.014 SE) at the 200 μL dose. DCE-MRI peak tumor enhancement at the 150 μL dose was significantly greater than both the 100 μL dose (p < 3.323E-08) and 200 μL dose (p < 0.0007396). Discussion: In this preliminary study, the 150 μL Gd-DTPA dose provided the greatest T1 weighted contrast enhancement, while minimizing negative T2* effects, in DCE-MRI scans of U87-derived tumors. Maximizing Gd-DTPA enhancement in DCE-MRI scans may assist development of a clinically robust (i.e., unambiguous) technique for PDT outcome assessment.

Stress responses of adolescent male and female rats exposed repeatedly to cat odor stimuli, and long-term enhancement of adult defensive behaviors.

PubMed

Wright, Lisa D; Muir, Katherine E; Perrot, Tara S

2013-07-01

In order to characterize the short- and long-term effects of repeated stressor exposure during adolescence, and to compare the effects of using two sources of cat odor as stressor stimuli, male and female adolescent rats (postnatal day (PND) ∼ 38-46) were exposed on five occasions to either a control stimulus, a cloth stimulus containing cat hair/dander, or a section of cat collar previously worn by a cat. Relative to control stimulus exposure, activity was suppressed and defensive behavior enhanced during exposure to either cat odor stimulus (most pervasively in rats exposed to the collar). Only cloth-exposed rats showed elevated levels of corticosterone (CORT), and only after repeated stressor exposure, but interestingly, rats exposed to the collar stimulus during adolescence continued to show increased behavioral indices of anxiety in adulthood. In this group, the time an individual spent in physical contact with a cagemate during the final adolescent exposure was negatively related to stress-induced CORT output in adulthood, which suggests that greater use of social support during adolescent stress may facilitate adult behavioral coping, without necessitating increased CORT release. These findings demonstrate that adolescent male and female rats respond defensively to cat odor stimuli across repeated exposures and that exposure to such stressors during adolescence can augment adult anxiety-like behavior in similar stressful conditions. These findings also suggest a potential role for social behavior during adolescent stressor exposure in mediating long-term outcomes. Copyright © 2012 Wiley Periodicals, Inc.

Human U2 snRNA Genes Exhibit a Persistently Open Transcriptional State and Promoter Disassembly at Metaphase▿

PubMed Central

Pavelitz, Thomas; Bailey, Arnold D.; Elco, Christopher P.; Weiner, Alan M.

2008-01-01

In mammals, small multigene families generate spliceosomal U snRNAs that are nearly as abundant as rRNA. Using the tandemly repeated human U2 genes as a model, we show by footprinting with DNase I and permanganate that nearly all sequences between the enhancer-like distal sequence element and the initiation site are protected during interphase whereas the upstream half of the U2 snRNA coding region is exposed. We also show by chromatin immunoprecipitation that the SNAPc complex, which binds the TATA-like proximal sequence element, is removed at metaphase but remains bound under conditions that induce locus-specific metaphase fragility of the U2 genes, such as loss of CSB, BRCA1, or BRCA2 function, treatment with actinomycin D, or overexpression of the tetrameric p53 C terminus. We propose that the U2 snRNA promoter establishes a persistently open state to facilitate rapid reinitiation and perhaps also to bypass TFIIH-dependent promoter melting; this open state would then be disassembled to allow metaphase chromatin condensation. PMID:18378697

Concerted evolution of the tandem array encoding primate U2 snRNA occurs in situ, without changing the cytological context of the RNU2 locus.

PubMed Central

Pavelitz, T; Rusché, L; Matera, A G; Scharf, J M; Weiner, A M

1995-01-01

In primates, the tandemly repeated genes encoding U2 small nuclear RNA evolve concertedly, i.e. the sequence of the U2 repeat unit is essentially homogeneous within each species but differs somewhat between species. Using chromosome painting and the NGFR gene as an outside marker, we show that the U2 tandem array (RNU2) has remained at the same chromosomal locus (equivalent to human 17q21) through multiple speciation events over > 35 million years leading to the Old World monkey and hominoid lineages. The data suggest that the U2 tandem repeat, once established in the primate lineage, contained sequence elements favoring perpetuation and concerted evolution of the array in situ, despite a pericentric inversion in chimpanzee, a reciprocal translocation in gorilla and a paracentric inversion in orang utan. Comparison of the 11 kb U2 repeat unit found in baboon and other Old World monkeys with the 6 kb U2 repeat unit in humans and other hominids revealed that an ancestral U2 repeat unit was expanded by insertion of a 5 kb retrovirus bearing 1 kb long terminal repeats (LTRs). Subsequent excision of the provirus by homologous recombination between the LTRs generated a 6 kb U2 repeat unit containing a solo LTR. Remarkably, both junctions between the human U2 tandem array and flanking chromosomal DNA at 17q21 fall within the solo LTR sequence, suggesting a role for the LTR in the origin or maintenance of the primate U2 array. Images PMID:7828589

Principles and Practices of Mature-Age Education at U3As

ERIC Educational Resources Information Center

Siedle, Rob

2011-01-01

A movement known as the Universities of the Third Age (U3As) provides educational, cultural and social services for mature-age people in Australia and internationally. This paper focuses on the educational courses run by U3As and discusses two basic questions: What are the expectations of learners who enrol in these classes? and How can tutors…

Assessing Hubbard-corrected AM05+ U and PBEsol+ U density functionals for strongly correlated oxides CeO 2 and Ce 2O 3

DOE PAGES

Weck, Philippe F.; Kim, Eunja

2016-09-12

The structure–property relationships of bulk CeO 2 and Ce 2O 3 have been investigated using AM05 and PBEsol exchange–correlation functionals within the frameworks of Hubbard-corrected density functional theory (DFT+ U) and density functional perturbation theory (DFPT+ U). Compared with conventional PBE+ U, RPBE+ U, PW91+ U and LDA+ U functionals, AM05+ U and PBEsol+ U describe experimental crystalline parameters and properties of CeO 2 and Ce 2O 3 with superior accuracy, especially when + U is chosen close to its value derived by the linear-response approach. Lastly, the present findings call for a reexamination of some of the problematic oxidemore » materials featuring strong f- and d-electron correlation using AM05+ U and PBEsol+ U.« less

Assessing Hubbard-corrected AM05+ U and PBEsol+ U density functionals for strongly correlated oxides CeO 2 and Ce 2O 3

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

Weck, Philippe F.; Kim, Eunja

The structure–property relationships of bulk CeO 2 and Ce 2O 3 have been investigated using AM05 and PBEsol exchange–correlation functionals within the frameworks of Hubbard-corrected density functional theory (DFT+ U) and density functional perturbation theory (DFPT+ U). Compared with conventional PBE+ U, RPBE+ U, PW91+ U and LDA+ U functionals, AM05+ U and PBEsol+ U describe experimental crystalline parameters and properties of CeO 2 and Ce 2O 3 with superior accuracy, especially when + U is chosen close to its value derived by the linear-response approach. Lastly, the present findings call for a reexamination of some of the problematic oxidemore » materials featuring strong f- and d-electron correlation using AM05+ U and PBEsol+ U.« less

U3As in Australia and New Zealand 2008: The Successful Ageing Organisations

ERIC Educational Resources Information Center

Swindell, Rick; Vassella, Ken; Morgan, Lee; Sayer, Tony

2009-01-01

The self-help University of the Third Age (U3A) is an adult education approach for older people in which all the teaching and administration is carried out by unpaid volunteers. The purpose of this study was to reveal some of the successful ageing characteristics of the 205 independent U3As in Australia and the 60 independent U3As in New Zealand…

Thymidylate synthase repeat polymorphisms and risk of neural tube defects in a population from the northern United Kingdom.

PubMed

Wilding, Craig S; Relton, Caroline L; Sutton, Matthew J; Jonas, Pat A; Lynch, Sally-Ann; Tawn, E Janet; Burn, John

2004-07-01

A 28-bp repeat polymorphism in the 5'UTR of the thymidylate synthase (TYMS) gene represents a candidate risk factor for neural tube defects (NTDs) due to involvement in folate-dependent homocysteine metabolism. Non-Hispanic, white, U.S. citizens carrying at least one 2x 28-bp repeat allele have recently been shown to be at a four-fold increased risk of spina bifida (SB). We investigated the association between this polymorphism and risk of NTD in families affected by NTDs and controls from the northern United Kingdom (UK). PCR was performed on genomic DNA extracted from blood or mouth swabs of family members affected by NTDs (mothers, fathers, and cases), and unaffected controls (mothers and infants) to determine the number of 28-bp repeat units within the promoter region of TYMS. Case-control and TDT analyses of the influence of TYMS genotype on risk of NTD, or NTD pregnancy, were conducted. Odds ratio (OR) analysis indicated that individuals carrying the 2x 28-bp repeat allele either in homozygous or heterozygous form, are not at increased risk of NTDs, or of having an NTD affected pregnancy. Control population allele frequencies are seen to be markedly different between the U.S. controls and those in this study. TYMS polymorphism appears to be not universally associated with NTD risk across Caucasian samples. The elevated risk of spina bifida in U.S. samples appears to be driven by an unusually low risk allele (2x 28 bp) frequency in control samples. Family based (TDT) testing of U.S. samples is therefore advocated.

Resveratrol strongly enhances the retinoic acid-induced superoxide generating activity via up-regulation of gp91-phox gene expression in U937 cells.

PubMed

Kikuchi, Hidehiko; Mimuro, Hitomi; Kuribayashi, Futoshi

2018-01-01

The membrane bound cytochrome b 558 composed of gp91-phox and p22-phox proteins, and cytosolic proteins p40-, p47-and p67-phox are important components of superoxide (O 2 - )-generating system in phagocytes. Here, we describe that resveratrol, a pleiotropic phytochemical belonging to the stilbenoids, dramatically activates the O 2 - -generating system during retinoic acid (RA)-induced differentiation of human monoblastic leukemia U937 cells to macrophage-like cells. When U937 cells were cultured in the presence of RA and resveratrol, the O 2 - -generating activity increased more than 5-fold compared with that in the absence of the latter. Semiquantitative RT-PCR showed that co-treatment with RA and resveratrol strongly enhanced transcription of the gp91-phox compared with those of the RA-treatment only. On the other hand, immunoblot analysis revealed that co-treatment with RA and resveratrol caused remarkable accumulation of protein levels of gp91-phox (to 4-fold), p22-phox (to 5-fold) and p47-phox (to 4-fold) compared with those of the RA-treatment alone. In addition, ChIP assay suggested that resveratrol participates in enhancing the gene expression of gp91-phox via promoting acetylation of Lys-9 residues and Lys-14 residues of histone H3 within chromatin around the promoter regions of the gene. These results suggested that resveratrol strongly enhances the RA-induced O 2 - -generating activity via up-regulation of gp91-phox gene expression in U937 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of High Si Content on U3Si2 Fuel Microstructure

NASA Astrophysics Data System (ADS)

Rosales, Jhonathan; van Rooyen, Isabella J.; Meher, Subhashish; Hoggan, Rita; Parga, Clemente; Harp, Jason

2018-02-01

The development of U3Si2 as an accident-tolerant nuclear fuel has gained research interest because of its promising high uranium density and improved thermal properties. In the present study, three samples of U3Si2 fuel with varying silicon content have been fabricated by a conventional powder metallurgical route. Microstructural characterization via scanning and transmission electron microscopy reveals the presence of other stoichiometry of uranium silicide such as USi and UO2 in both samples. The detailed phase analysis by x-ray diffraction shows the presence of secondary phases, such as USi, U3Si, and UO2. The samples with higher concentrations of silicon content of 7.5 wt.% display additional elemental Si. These samples also possess an increased amount of the USi phase as compared to that in the conventional sample with 7.3 wt.% silicon. The optimization of U3Si2 fuel performance through the understanding of the role of Si content on its microstructure has been discussed.

Repeatless and repeat-based centromeres in potato: implications for centromere evolution.

PubMed

Gong, Zhiyun; Wu, Yufeng; Koblízková, Andrea; Torres, Giovana A; Wang, Kai; Iovene, Marina; Neumann, Pavel; Zhang, Wenli; Novák, Petr; Buell, C Robin; Macas, Jirí; Jiang, Jiming

2012-09-01

Centromeres in most higher eukaryotes are composed of long arrays of satellite repeats. By contrast, most newly formed centromeres (neocentromeres) do not contain satellite repeats and instead include DNA sequences representative of the genome. An unknown question in centromere evolution is how satellite repeat-based centromeres evolve from neocentromeres. We conducted a genome-wide characterization of sequences associated with CENH3 nucleosomes in potato (Solanum tuberosum). Five potato centromeres (Cen4, Cen6, Cen10, Cen11, and Cen12) consisted primarily of single- or low-copy DNA sequences. No satellite repeats were identified in these five centromeres. At least one transcribed gene was associated with CENH3 nucleosomes. Thus, these five centromeres structurally resemble neocentromeres. By contrast, six potato centromeres (Cen1, Cen2, Cen3, Cen5, Cen7, and Cen8) contained megabase-sized satellite repeat arrays that are unique to individual centromeres. The satellite repeat arrays likely span the entire functional cores of these six centromeres. At least four of the centromeric repeats were amplified from retrotransposon-related sequences and were not detected in Solanum species closely related to potato. The presence of two distinct types of centromeres, coupled with the boom-and-bust cycles of centromeric satellite repeats in Solanum species, suggests that repeat-based centromeres can rapidly evolve from neocentromeres by de novo amplification and insertion of satellite repeats in the CENH3 domains.

The cumulative analgesic effect of repeated electroacupuncture involves synaptic remodeling in the hippocampal CA3 region☆

PubMed Central

Xu, Qiuling; Liu, Tao; Chen, Shuping; Gao, Yonghui; Wang, Junying; Qiao, Lina; Liu, Junling

2012-01-01

In the present study, we examined the analgesic effect of repeated electroacupuncture at bilateral Zusanli (ST36) and Yanglingquan (GB34) once a day for 14 consecutive days in a rat model of chronic sciatic nerve constriction injury-induced neuropathic pain. In addition, concomitant changes in calcium/calmodulin-dependent protein kinase II expression and synaptic ultrastructure of neurons in the hippocampal CA3 region were examined. The thermal pain threshold (paw withdrawal latency) was increased significantly in both groups at 2 weeks after electroacupuncture intervention compared with 2 days of electroacupuncture. In ovariectomized rats with chronic constriction injury, the analgesic effect was significantly reduced. Electroacupuncture for 2 weeks significantly diminished the injury-induced increase in synaptic cleft width and thinning of the postsynaptic density, and it significantly suppressed the down-regulation of intracellular calcium/calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. Repeated electroacupuncture intervention had a cumulative analgesic effect on injury-induced neuropathic pain reactions, and it led to synaptic remodeling of hippocampal neurons and upregulated calcium/calmodulin-dependent protein kinase II expression in the hippocampal CA3 region. PMID:25657670

22 CFR 203.3 - U.S. PVO conditions of registration.

Code of Federal Regulations, 2010 CFR

2010-04-01

... U.S. organizations. The first four Conditions relate to whether an organization meets the definition... Section 501(C)(3) of the Internal Revenue Code; and (2) Is not a university, college, accredited degree... registration, conducts international program activities within the last three years. For example, if a U.S. PVO...

22 CFR 203.3 - U.S. PVO conditions of registration.

Code of Federal Regulations, 2013 CFR

2013-04-01

... U.S. organizations. The first four Conditions relate to whether an organization meets the definition... Section 501(C)(3) of the Internal Revenue Code; and (2) Is not a university, college, accredited degree... registration, conducts international program activities within the last three years. For example, if a U.S. PVO...

22 CFR 203.3 - U.S. PVO conditions of registration.

Code of Federal Regulations, 2014 CFR

2014-04-01

... U.S. organizations. The first four Conditions relate to whether an organization meets the definition... Section 501(C)(3) of the Internal Revenue Code; and (2) Is not a university, college, accredited degree... registration, conducts international program activities within the last three years. For example, if a U.S. PVO...

22 CFR 203.3 - U.S. PVO conditions of registration.

Code of Federal Regulations, 2011 CFR

2011-04-01

... U.S. organizations. The first four Conditions relate to whether an organization meets the definition... Section 501(C)(3) of the Internal Revenue Code; and (2) Is not a university, college, accredited degree... registration, conducts international program activities within the last three years. For example, if a U.S. PVO...

22 CFR 203.3 - U.S. PVO conditions of registration.

Code of Federal Regulations, 2012 CFR

2012-04-01

... U.S. organizations. The first four Conditions relate to whether an organization meets the definition... Section 501(C)(3) of the Internal Revenue Code; and (2) Is not a university, college, accredited degree... registration, conducts international program activities within the last three years. For example, if a U.S. PVO...

Perturbation of the Akt/Gsk3-β signalling pathway is common to Drosophila expressing expanded untranslated CAG, CUG and AUUCU repeat RNAs.

PubMed

van Eyk, Clare L; O'Keefe, Louise V; Lawlor, Kynan T; Samaraweera, Saumya E; McLeod, Catherine J; Price, Gareth R; Venter, Deon J; Richards, Robert I

2011-07-15

Recent evidence supports a role for RNA as a common pathogenic agent in both the 'polyglutamine' and 'untranslated' dominant expanded repeat disorders. One feature of all repeat sequences currently associated with disease is their predicted ability to form a hairpin secondary structure at the RNA level. In order to investigate mechanisms by which hairpin-forming repeat RNAs could induce neurodegeneration, we have looked for alterations in gene transcript levels as hallmarks of the cellular response to toxic hairpin repeat RNAs. Three disease-associated repeat sequences--CAG, CUG and AUUCU--were specifically expressed in the neurons of Drosophila and resultant common transcriptional changes assessed by microarray analyses. Transcripts that encode several components of the Akt/Gsk3-β signalling pathway were altered as a consequence of expression of these repeat RNAs, indicating that this pathway is a component of the neuronal response to these pathogenic RNAs and may represent an important common therapeutic target in this class of diseases.

MutSβ abundance and Msh3 ATP hydrolysis activity are important drivers of CTG•CAG repeat expansions

PubMed Central

Keogh, Norma; Chan, Kara Y.; Li, Guo-Min

2017-01-01

Abstract CTG•CAG repeat expansions cause at least twelve inherited neurological diseases. Expansions require the presence, not the absence, of the mismatch repair protein MutSβ (Msh2-Msh3 heterodimer). To evaluate properties of MutSβ that drive expansions, previous studies have tested under-expression, ATPase function or polymorphic variants of Msh2 and Msh3, but in disparate experimental systems. Additionally, some variants destabilize MutSβ, potentially masking the effects of biochemical alterations of the variations. Here, human Msh3 was mutated to selectively inactivate MutSβ. Msh3−/− cells are severely defective for CTG•CAG repeat expansions but show full activity on contractions. Msh3−/− cells provide a single, isogenic system to add back Msh3 and test key biochemical features of MutSβ on expansions. Msh3 overexpression led to high expansion activity and elevated levels of MutSβ complex, indicating that MutSβ abundance drives expansions. An ATPase-defective Msh3 expressed at normal levels was as defective in expansions as Msh3−/− cells, indicating that Msh3 ATPase function is critical for expansions. Expression of two Msh3 polymorphic variants at normal levels showed no detectable change in expansions, suggesting these polymorphisms primarily affect Msh3 protein stability, not activity. In summary, CTG•CAG expansions are limited by the abundance of MutSβ and rely heavily on Msh3 ATPase function. PMID:28973443

MutSβ abundance and Msh3 ATP hydrolysis activity are important drivers of CTG•CAG repeat expansions.

PubMed

Keogh, Norma; Chan, Kara Y; Li, Guo-Min; Lahue, Robert S

2017-09-29

CTG•CAG repeat expansions cause at least twelve inherited neurological diseases. Expansions require the presence, not the absence, of the mismatch repair protein MutSβ (Msh2-Msh3 heterodimer). To evaluate properties of MutSβ that drive expansions, previous studies have tested under-expression, ATPase function or polymorphic variants of Msh2 and Msh3, but in disparate experimental systems. Additionally, some variants destabilize MutSβ, potentially masking the effects of biochemical alterations of the variations. Here, human Msh3 was mutated to selectively inactivate MutSβ. Msh3-/- cells are severely defective for CTG•CAG repeat expansions but show full activity on contractions. Msh3-/- cells provide a single, isogenic system to add back Msh3 and test key biochemical features of MutSβ on expansions. Msh3 overexpression led to high expansion activity and elevated levels of MutSβ complex, indicating that MutSβ abundance drives expansions. An ATPase-defective Msh3 expressed at normal levels was as defective in expansions as Msh3-/- cells, indicating that Msh3 ATPase function is critical for expansions. Expression of two Msh3 polymorphic variants at normal levels showed no detectable change in expansions, suggesting these polymorphisms primarily affect Msh3 protein stability, not activity. In summary, CTG•CAG expansions are limited by the abundance of MutSβ and rely heavily on Msh3 ATPase function. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Comparison of thermal compatibility between atomized and comminuted U{sub 3}Si dispersion fuels

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

Ryu, Woo-Seog; Park, Jong-Man; Kim, Chang-Kyu

1997-08-01

Thermal compatibility of atomized U{sub 3}Si dispersion fuels were evaluated up to 2600 hours in the temperature range from 250 to 500{degrees}C, and compared with that of comminuted U{sub 3}Si. Atomized U{sub 3}Si showed better performance in terms of volume expansion of fuel meats. The reaction zone of U{sub 3}Si and Al occurred along the grain boundaries and deformation bands in U{sub 3}Si particles. Pores around fuel particles appeared at high temperature or after long-term annealing tests to remain diffusion paths over the trench of the pores. The constraint effects of cladding on fuel rod suppressed the fuel meat, andmore » reduced the volume expansion.« less

Towards gauge coupling unification in left-right symmetric SU (3 )c×SU (3 )L×SU (3 )R×U (1 )X theories

NASA Astrophysics Data System (ADS)

Hati, Chandan; Patra, Sudhanwa; Reig, Mario; Valle, José W. F.; Vaquera-Araujo, C. A.

2017-07-01

We consider the possibility of gauge coupling unification within the simplest realizations of the SU (3 )c×SU (3 )L×SU (3 )R×U (1 )X gauge theory. We present a first exploration of the renormalization group equations governing the "bottom-up" evolution of the gauge couplings in a generic model with free normalization for the generators. Interestingly, we find that for a SU (3 )c×SU (3 )L×SU (3 )R×U (1 )X symmetry breaking scale MX as low as a few TeV one can achieve unification in the presence of leptonic octets. We briefly comment on possible grand unified theory frameworks which can embed the SU (3 )c×SU (3 )L×SU (3 )R×U (1 )X model as well as possible implications, such as lepton flavor violating physics at the LHC.

siRNAs from an X-linked satellite repeat promote X-chromosome recognition in Drosophila melanogaster.

PubMed

Menon, Debashish U; Coarfa, Cristian; Xiao, Weimin; Gunaratne, Preethi H; Meller, Victoria H

2014-11-18

Highly differentiated sex chromosomes create a lethal imbalance in gene expression in one sex. To accommodate hemizygosity of the X chromosome in male fruit flies, expression of X-linked genes increases twofold. This is achieved by the male- specific lethal (MSL) complex, which modifies chromatin to increase expression. Mutations that disrupt the X localization of this complex decrease the expression of X-linked genes and reduce male survival. The mechanism that restricts the MSL complex to X chromatin is not understood. We recently reported that the siRNA pathway contributes to localization of the MSL complex, raising questions about the source of the siRNAs involved. The X-linked 1.688 g/cm(3) satellite related repeats (1.688(X) repeats) are restricted to the X chromosome and produce small RNA, making them an attractive candidate. We tested RNA from these repeats for a role in dosage compensation and found that ectopic expression of single-stranded RNAs from 1.688(X) repeats enhanced the male lethality of mutants with defective X recognition. In contrast, expression of double-stranded hairpin RNA from a 1.688(X) repeat generated abundant siRNA and dramatically increased male survival. Consistent with improved survival, X localization of the MSL complex was largely restored in these males. The striking distribution of 1.688(X) repeats, which are nearly exclusive to the X chromosome, suggests that these are cis-acting elements contributing to identification of X chromatin.

Determination of elastic properties of polycrystalline U 3Si 2 using resonant ultrasound spectroscopy

DOE PAGES

Carvajal-Nunez, Ursula; Saleh, Tarik A.; White, Joshua Taylor; ...

2017-11-10

For this research, the elastic properties of U 3Si 2 at room temperature have been measured via resonant ultrasound spectroscopy. Results show that the average value of Young's and the bulk modulus for U 3Si 2 are 130.4±0.5 and 68.3±0.5 GPa, respectively. Further, a numerical model to assess thermal stress in an operating fuel is evaluated. Lastly, the thermal stress evolved in U 3Si 2 is compared to UO 2 to facilitate an estimation of the probability of crack formation in U 3Si 2 under representative light water reactor operating conditions.

Determination of elastic properties of polycrystalline U 3Si 2 using resonant ultrasound spectroscopy

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

Carvajal-Nunez, Ursula; Saleh, Tarik A.; White, Joshua Taylor

For this research, the elastic properties of U 3Si 2 at room temperature have been measured via resonant ultrasound spectroscopy. Results show that the average value of Young's and the bulk modulus for U 3Si 2 are 130.4±0.5 and 68.3±0.5 GPa, respectively. Further, a numerical model to assess thermal stress in an operating fuel is evaluated. Lastly, the thermal stress evolved in U 3Si 2 is compared to UO 2 to facilitate an estimation of the probability of crack formation in U 3Si 2 under representative light water reactor operating conditions.

Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats

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

Rubinsztein, D.C.; Leggo, J.; Whittaker, J.L.

1996-07-01

Abnormal CAG expansions in the IT-15 gene are associated with Huntington disease (HD). In the diagnostic setting it is necessary to define the limits of the CAG size ranges on normal and HD-associated chromosomes. Most large analyses that defined the limits of the normal and pathological size ranges employed PCR assays, which included the CAG repeats and a CCG repeat tract that was thought to be invariant. Many of these experiments found an overlap between the normal and disease size ranges. Subsequent findings that the CCG repeats vary by 9 trinucleotide lengths suggested that the limits of the normal andmore » disease size ranges should be reevaluated with assays that exclude the CCG polymorphism. Since patients with between 30 and 40 repeats are rare, a consortium was assembled to collect such individuals. All 178 samples were reanalyzed in Cambridge by using assays specific for the CAG repeats. We have optimized methods for reliable sizing of CAG repeats and show cases that demonstrate the dangers of using PCR assays that include both the CAG and CCG polymorphisms. Seven HD patients had 36 repeats, which confirms that this allele is associated with disease. Individuals without apparent symptoms or signs of HD were found at 36 repeats (aged 74, 78, 79, and 87 years), 37 repeats (aged 69 years), 38 repeats (aged 69 and 90 years), and 39 repeats (aged 67, 90, and 95 years). The detailed case histories of an exceptional case from this series will be presented: a 95-year-old man with 39 repeats who did not have classical features of HD. The apparently healthy survival into old age of some individuals with 36-39 repeats suggests that the HD mutation may not always be fully penetrant. 26 refs., 3 figs., 1 tab.« less

SCA8 Repeat Expansion: Large CTA/CTG Repeat Alleles Are More Common in Ataxic Patients, Including Those with SCA6

PubMed Central

Izumi, Yuishin; Maruyama, Hirofumi; Oda, Masaya; Morino, Hiroyuki; Okada, Takayuki; Ito, Hidefumi; Sasaki, Iwao; Tanaka, Hiroyasu; Komure, Osamu; Udaka, Fukashi; Nakamura, Shigenobu; Kawakami, Hideshi

2003-01-01

We analyzed the SCA8 CTA/CTG repeat in a large group of Japanese subjects. The frequency of large alleles (85–399 CTA/CTG repeats) was 1.9% in spinocerebellar ataxia (SCA), 0.4% in Parkinson disease, 0.3% in Alzheimer disease, and 0% in a healthy control group; the frequency was significantly higher in the group with SCA than in the control group. Homozygotes for large alleles were observed only in the group with SCA. In five patients with SCA from two families, a large SCA8 CTA/CTG repeat and a large SCA6 CAG repeat coexisted. Age at onset was correlated with SCA8 repeats rather than SCA6 repeats in these five patients. In one of these families, at least one patient showed only a large SCA8 CTA/CTG repeat allele, with no large SCA6 CAG repeat allele. We speculate that the presence of a large SCA8 CTA/CTG repeat allele influences the function of channels such as α1A-voltage–dependent calcium channel through changing or aberrant splicing, resulting in the development of cerebellar ataxia, especially in homozygous patients. PMID:12545428

SCA8 repeat expansion: large CTA/CTG repeat alleles are more common in ataxic patients, including those with SCA6.

PubMed

Izumi, Yuishin; Maruyama, Hirofumi; Oda, Masaya; Morino, Hiroyuki; Okada, Takayuki; Ito, Hidefumi; Sasaki, Iwao; Tanaka, Hiroyasu; Komure, Osamu; Udaka, Fukashi; Nakamura, Shigenobu; Kawakami, Hideshi

2003-03-01

We analyzed the SCA8 CTA/CTG repeat in a large group of Japanese subjects. The frequency of large alleles (85-399 CTA/CTG repeats) was 1.9% in spinocerebellar ataxia (SCA), 0.4% in Parkinson disease, 0.3% in Alzheimer disease, and 0% in a healthy control group; the frequency was significantly higher in the group with SCA than in the control group. Homozygotes for large alleles were observed only in the group with SCA. In five patients with SCA from two families, a large SCA8 CTA/CTG repeat and a large SCA6 CAG repeat coexisted. Age at onset was correlated with SCA8 repeats rather than SCA6 repeats in these five patients. In one of these families, at least one patient showed only a large SCA8 CTA/CTG repeat allele, with no large SCA6 CAG repeat allele. We speculate that the presence of a large SCA8 CTA/CTG repeat allele influences the function of channels such as alpha(1A)-voltage-dependent calcium channel through changing or aberrant splicing, resulting in the development of cerebellar ataxia, especially in homozygous patients.

Nuclear Resonance Fluorescence of U-235 above 3 MeV

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

Warren, Glen A.; Caggiano, Joseph A.; Miller, Erin A.

Pacific Northwest National Laboratory and Passport Systems have collaborated to conduct measurements to search for a nuclear resonance fluorescence response of U-235 from 3 to 5 MeV using an 8 g sample of highly enriched uranium. These new measurements complement previously reported measurements below 3 MeV. Preliminary analysis indicates that no strong resonances exist for U-235 in this energy range. A second set of measurements focused on a signature search in the 5 to 10 MeV range is still under analysis.

Pilot scale repeated fed-batch fermentation processes of the wine yeast Dekkera bruxellensis for mass production of resveratrol from Polygonum cuspidatum.

PubMed

Kuo, Hsiao-Ping; Wang, Reuben; Lin, Yi-Sheng; Lai, Jinn-Tsyy; Lo, Yi-Chen; Huang, Shyue-Tsong

2017-11-01

Resveratrol has long been used as an ingredient in functional foods. Currently, Polygonum cuspidatum extract is the greatest natural source for resveratrol because of high concentrations of glycosidic-linked resveratrol. Thus, developing a cost-effective procedure to hydrolyze glucoside could substantially enhance resveratrol production from P. cuspidatum. This study selected Dekkera bruxellensis from several microorganisms based on its bioconversion and enzyme-specific activities. We demonstrated that the cells could be reused at least nine times while maintaining an average of 180.67U/L β-glucosidase activity. The average resveratrol bioconversion efficiency within five rounds of repeated usage was 108.77±0.88%. This process worked effectively when the volume was increased to 1200L, a volume at which approximately 35mgL -1 h -1 resveratrol per round was produced. This repeated fed-batch bioconversion process for resveratrol production is comparable to enzyme or cell immobilization strategies in terms of reusing cycles, but without incurring additional costs for immobilization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigating the Relation between Moral Self-Enhancement and Self-Deception: A Cross-Cultural Study of U.S. and Chinese College Students

ERIC Educational Resources Information Center

Liu, Ying

2012-01-01

Testing an evolutionary framework, this study examined moral self-enhancement in relation to self-deception and self-construal in a cross-cultural context. The participants included 127 U.S. and 107 Chinese college students. The results demonstrated that moral self-enhancement is not a characteristic unique to individualistic ideology but rather a…

Solution of hydrogen in accident tolerant fuel candidate material: U3Si2

NASA Astrophysics Data System (ADS)

Middleburgh, S. C.; Claisse, A.; Andersson, D. A.; Grimes, R. W.; Olsson, P.; Mašková, S.

2018-04-01

Hydrogen uptake and accommodation into U3Si2, a candidate accident-tolerant fuel system, has been modelled on the atomic scale using the density functional theory. The solution energy of multiple H atoms is computed, reaching a stoichiometry of U3Si2H2 which has been experimentally observed in previous work (reported as U3Si2H1.8). The absorption of hydrogen is found to be favourable up to U3Si2H2 and the associated volume change is computed, closely matching experimental data. Entropic effects are considered to assess the dissociation temperature of H2, estimated to be at ∼800 K - again in good agreement with the experimentally observed transition temperature.

Analysis of an Organisation: A University of the Third Age (U3A), Mornington, Victoria

ERIC Educational Resources Information Center

Small, Michael

2017-01-01

The purpose of this paper is two fold: to look at Mornington U3A in organisational terms and then look at U3AM as a loosely coupled system. One outcome of the study would be to undertake further analyses of U3As in Victoria to determine the levels of bureaucracy under which each operates. Questions to be asked: are U3As in Victoria operating as…

Large-scale assessment of polyglutamine repeat expansions in Parkinson disease

PubMed Central

Wang, Lisa; Aasly, Jan O.; Annesi, Grazia; Bardien, Soraya; Bozi, Maria; Brice, Alexis; Carr, Jonathan; Chung, Sun J.; Clarke, Carl; Crosiers, David; Deutschländer, Angela; Eckstein, Gertrud; Farrer, Matthew J.; Goldwurm, Stefano; Garraux, Gaetan; Hadjigeorgiou, Georgios M.; Hicks, Andrew A.; Hattori, Nobutaka; Klein, Christine; Jeon, Beom; Kim, Yun J.; Lesage, Suzanne; Lin, Juei-Jueng; Lynch, Timothy; Lichtner, Peter; Lang, Anthony E.; Mok, Vincent; Jasinska-Myga, Barbara; Mellick, George D.; Morrison, Karen E.; Opala, Grzegorz; Pihlstrøm, Lasse; Pramstaller, Peter P.; Park, Sung S.; Quattrone, Aldo; Rogaeva, Ekaterina; Ross, Owen A.; Stefanis, Leonidas; Stockton, Joanne D.; Silburn, Peter A.; Theuns, Jessie; Tan, Eng K.; Tomiyama, Hiroyuki; Toft, Mathias; Van Broeckhoven, Christine; Uitti, Ryan J.; Wirdefeldt, Karin; Wszolek, Zbigniew; Xiromerisiou, Georgia; Yueh, Kuo-Chu; Zhao, Yi; Gasser, Thomas; Maraganore, Demetrius M.; Krüger, Rejko

2015-01-01

Objectives: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD). Methods: We invited researchers from the Genetic Epidemiology of Parkinson's Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations. Results: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci. Conclusions: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD. PMID:26354989

Tau-U: A Quantitative Approach for Analysis of Single-Case Experimental Data in Aphasia.

PubMed

Lee, Jaime B; Cherney, Leora R

2018-03-01

Tau-U is a quantitative approach for analyzing single-case experimental design (SCED) data. It combines nonoverlap between phases with intervention phase trend and can correct for a baseline trend (Parker, Vannest, & Davis, 2011). We demonstrate the utility of Tau-U by comparing it with the standardized mean difference approach (Busk & Serlin, 1992) that is widely reported within the aphasia SCED literature. Repeated writing measures from 3 participants with chronic aphasia who received computer-based writing treatment are analyzed visually and quantitatively using both Tau-U and the standardized mean difference approach. Visual analysis alone was insufficient for determining an effect between the intervention and writing improvement. The standardized mean difference yielded effect sizes ranging from 4.18 to 26.72 for trained items and 1.25 to 3.20 for untrained items. Tau-U yielded significant (p < .05) effect sizes for 2 of 3 participants for trained probes and 1 of 3 participants for untrained probes. A baseline trend correction was applied to data from 2 of 3 participants. Tau-U has the unique advantage of allowing for the correction of an undesirable baseline trend. Although further study is needed, Tau-U shows promise as a quantitative approach to augment visual analysis of SCED data in aphasia.

Repeat-containing protein effectors of plant-associated organisms

PubMed Central

Mesarich, Carl H.; Bowen, Joanna K.; Hamiaux, Cyril; Templeton, Matthew D.

2015-01-01

Many plant-associated organisms, including microbes, nematodes, and insects, deliver effector proteins into the apoplast, vascular tissue, or cell cytoplasm of their prospective hosts. These effectors function to promote colonization, typically by altering host physiology or by modulating host immune responses. The same effectors however, can also trigger host immunity in the presence of cognate host immune receptor proteins, and thus prevent colonization. To circumvent effector-triggered immunity, or to further enhance host colonization, plant-associated organisms often rely on adaptive effector evolution. In recent years, it has become increasingly apparent that several effectors of plant-associated organisms are repeat-containing proteins (RCPs) that carry tandem or non-tandem arrays of an amino acid sequence or structural motif. In this review, we highlight the diverse roles that these repeat domains play in RCP effector function. We also draw attention to the potential role of these repeat domains in adaptive evolution with regards to RCP effector function and the evasion of effector-triggered immunity. The aim of this review is to increase the profile of RCP effectors from plant-associated organisms. PMID:26557126

Repeat-containing protein effectors of plant-associated organisms.

PubMed

Mesarich, Carl H; Bowen, Joanna K; Hamiaux, Cyril; Templeton, Matthew D

2015-01-01

Many plant-associated organisms, including microbes, nematodes, and insects, deliver effector proteins into the apoplast, vascular tissue, or cell cytoplasm of their prospective hosts. These effectors function to promote colonization, typically by altering host physiology or by modulating host immune responses. The same effectors however, can also trigger host immunity in the presence of cognate host immune receptor proteins, and thus prevent colonization. To circumvent effector-triggered immunity, or to further enhance host colonization, plant-associated organisms often rely on adaptive effector evolution. In recent years, it has become increasingly apparent that several effectors of plant-associated organisms are repeat-containing proteins (RCPs) that carry tandem or non-tandem arrays of an amino acid sequence or structural motif. In this review, we highlight the diverse roles that these repeat domains play in RCP effector function. We also draw attention to the potential role of these repeat domains in adaptive evolution with regards to RCP effector function and the evasion of effector-triggered immunity. The aim of this review is to increase the profile of RCP effectors from plant-associated organisms.

Serine 192 in the tiny RS repeat of the adenoviral L4-33K splicing enhancer protein is essential for function and reorganization of the protein to the periphery of viral replication centers

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

Oestberg, Sara, E-mail: sara.ostberg@imbim.uu.se; Toermaenen Persson, Heidi, E-mail: heidi.tormanen.persson@imbim.uu.se; Akusjaervi, Goeran, E-mail: goran.akusjarvi@imbim.uu.se

2012-11-25

The adenovirus L4-33K protein is a key regulator involved in the temporal shift from early to late pattern of mRNA expression from the adenovirus major late transcription unit. L4-33K is a virus-encoded alternative splicing factor, which enhances processing of 3 Prime splice sites with a weak sequence context. Here we show that L4-33K expressed from a plasmid is localized at the nuclear margin of uninfected cells. During an infection L4-33K is relocalized to the periphery of E2A-72K containing viral replication centers. We also show that serine 192 in the tiny RS repeat of the conserved carboxy-terminus of L4-33K, which ismore » critical for the splicing enhancer function of L4-33K, is necessary for the nuclear localization and redistribution of the protein to viral replication sites. Collectively, our results show a good correlation between the activity of L4-33K as a splicing enhancer protein and its localization to the periphery of viral replication centers.« less

The intracellular nucleotide binding leucine-rich repeat receptor - SlNRC4a enhances immune signaling elicited by extracellular perception.

PubMed

Leibman-Markus, Meirav; Pizarro, Lorena; Schuster, Silvia; Lin, Z J Daniel; Gershony, Ofir; Bar, Maya; Coaker, Gitta; Avni, Adi

2018-05-23

Plant recognition and defense against pathogens employs a two-tiered perception system. Surface localized pattern recognition receptors (PRRs) act to recognize microbial features, while intracellular nucleotide binding leucine-rich repeat receptors (NLRs) directly or indirectly recognize pathogen effectors inside host cells. Employing the tomato PRR LeEIX2/EIX model system, we explored the molecular mechanism of signaling pathways. We identified an NLR that can associate with LeEIX2, termed SlNRC4a (NB-LRR Required for HR-associated Cell death-4). Co-immunoprecipitation demonstrates that SlNRC4a is able to associate with different PRRs. Physiological assays with specific elicitors revealed that SlNRC4a generally alters PRR-mediated responses. SlNRC4a overexpression enhances defense responses while silencing SlNRC4 reduces plant immunity. Moreover, the coiled-coil domain of SlNRC4a is able to associate with LeEIX2 and is sufficient to enhance responses upon EIX perception. Based on these findings, we propose that SlNRC4a acts as a non-canonical positive regulator of immunity mediated by diverse PRRs. Thus, SlNRC4a could link both intracellular and extracellular immune perception. This article is protected by copyright. All rights reserved.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 with improved proof-reading enhances homology-directed repair.

PubMed

Kato-Inui, Tomoko; Takahashi, Gou; Hsu, Szuyin; Miyaoka, Yuichiro

2018-05-18

Genome editing using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) predominantly induces non-homologous end joining (NHEJ), which generates random insertions or deletions, whereas homology-directed repair (HDR), which generates precise recombination products, is useful for wider applications. However, the factors that determine the ratio of HDR to NHEJ products after CRISPR/Cas9 editing remain unclear, and methods by which the proportion of HDR products can be increased have not yet been fully established. We systematically analyzed the HDR and NHEJ products after genome editing using various modified guide RNAs (gRNAs) and Cas9 variants with an enhanced conformational checkpoint to improve the fidelity at endogenous gene loci in HEK293T cells and HeLa cells. We found that these modified gRNAs and Cas9 variants were able to enhance HDR in both single-nucleotide substitutions and a multi-kb DNA fragment insertion. Our results suggest that the original CRISPR/Cas9 system from the bacterial immune system is not necessarily the best option for the induction of HDR in genome editing and indicate that the modulation of the kinetics of conformational checkpoints of Cas9 can optimize the HDR/NHEJ ratio.

Alternative exon definition events control the choice between nuclear retention and cytoplasmic export of U11/U12-65K mRNA

PubMed Central

Verbeeren, Jens; Verma, Bhupendra

2017-01-01

Cellular homeostasis of the minor spliceosome is regulated by a negative feed-back loop that targets U11-48K and U11/U12-65K mRNAs encoding essential components of the U12-type intron-specific U11/U12 di-snRNP. This involves interaction of the U11 snRNP with an evolutionarily conserved splicing enhancer giving rise to unproductive mRNA isoforms. In the case of U11/U12-65K, this mechanism controls the length of the 3′ untranslated region (3′UTR). We show that this process is dynamically regulated in developing neurons and some other cell types, and involves a binary switch between translation-competent mRNAs with a short 3′UTR to non-productive isoforms with a long 3′UTR that are retained in the nucleus or/and spliced to the downstream amylase locus. Importantly, the choice between these alternatives is determined by alternative terminal exon definition events regulated by conserved U12- and U2-type 5′ splice sites as well as sequence signals used for pre-mRNA cleavage and polyadenylation. We additionally show that U11 snRNP binding to the U11/U12-65K mRNA species with a long 3′UTR is required for their nuclear retention. Together, our studies uncover an intricate molecular circuitry regulating the abundance of a key spliceosomal protein and shed new light on the mechanisms limiting the export of non-productively spliced mRNAs from the nucleus to the cytoplasm. PMID:28549066

Alternative exon definition events control the choice between nuclear retention and cytoplasmic export of U11/U12-65K mRNA.

PubMed

Verbeeren, Jens; Verma, Bhupendra; Niemelä, Elina H; Yap, Karen; Makeyev, Eugene V; Frilander, Mikko J

2017-05-01

Cellular homeostasis of the minor spliceosome is regulated by a negative feed-back loop that targets U11-48K and U11/U12-65K mRNAs encoding essential components of the U12-type intron-specific U11/U12 di-snRNP. This involves interaction of the U11 snRNP with an evolutionarily conserved splicing enhancer giving rise to unproductive mRNA isoforms. In the case of U11/U12-65K, this mechanism controls the length of the 3' untranslated region (3'UTR). We show that this process is dynamically regulated in developing neurons and some other cell types, and involves a binary switch between translation-competent mRNAs with a short 3'UTR to non-productive isoforms with a long 3'UTR that are retained in the nucleus or/and spliced to the downstream amylase locus. Importantly, the choice between these alternatives is determined by alternative terminal exon definition events regulated by conserved U12- and U2-type 5' splice sites as well as sequence signals used for pre-mRNA cleavage and polyadenylation. We additionally show that U11 snRNP binding to the U11/U12-65K mRNA species with a long 3'UTR is required for their nuclear retention. Together, our studies uncover an intricate molecular circuitry regulating the abundance of a key spliceosomal protein and shed new light on the mechanisms limiting the export of non-productively spliced mRNAs from the nucleus to the cytoplasm.

Nouvelle serie d'oxydes derives de la structure de α-U 3U 8: MIIUMo 4O 16

NASA Astrophysics Data System (ADS)

Lee, M. R.; Jaulmes, S.

1987-04-01

A new family of isotypical oxides MIIUMo 4O 16 ( MII = Mg,Mn,Cd,Ca,Hg,Sr,Pb) is identified. The structure of the compound with Ca was determined by X-ray diffraction. It is triclinic, space group P overline1 with a = 13.239(5) Å, b = 6.651(2) Å, c = 8.236(3) Å, α = 90°00(4), β = 90°38(4), γ = 120°16(3), Z = 2. The final index and the weighted Rw index are 0.049 and 0.040, respectively. The cell is related to the orthorhombic one of α-U 3O 8: a = 2 a0, b = -( a0 + b0)/2, c = 2 c0. The structure, reminiscent of that of α-U 3O 8, consists of chains of [Ca,U]O 7 pentagonal bipyramids and MoO 6 octahedra, running parallel to the c axis. The UO distances along the UOCaO chains are shortened to 1.77(1) Å. The uranyl ion was characterized by its IR spectrum.

(234)U/(238)U signatures associated with uranium ore bodies: part 3 Koongarra.

PubMed

Lowson, Richard T

2013-04-01

The Koongarra ore body is an early Proterozoic U ore body in the Alligator Rivers U province, Northern Territory, Australia. It has surface expression with a redox front located ∼30 m below the surface. The (234)U/(238)U activity ratios (AR) for the ground water and the amorphous phase of the solid have been analysed for the ore zone and dispersion halo as a function of depth. The results display a (234)U/(238)U AR signature with depth which may be common to all U ore bodies. The (234)U/(238)U AR is depressed below secular equilibrium in the weathered material above the redox front; rises significantly above secular equilibrium in the vicinity of the redox front; and is followed by a gradual decrease with depth below the redox front. The amplitude of the profile is a function of local conditions. A model is proposed for the signature in which oxidising waters preferentially leach the (234)U sites at the redox front due to preconditioning of the (234)U sites by α recoil during the decay of (23)(8)U to (23)(4)U. Mass balance requires the solid material left behind the redox front to have a (234)U/(238)U AR reduced below 1. Local second order effects may be superimposed on the signature. The signature may have application to calibrating scenarios for nuclear waste repositories, assisting in understanding historical climates, economic evaluation of U ore bodies and U exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effects of the repeated administration of adenosine and heparin on myocardial perfusion in patients with chronic stable angina pectoris.

PubMed

Barron, H V; Sciammarella, M G; Lenihan, K; Michaels, A D; Botvinick, E H

2000-01-01

The mechanism by which ischemia stimulates angiogenesis is unknown. Adenosine is released during myocardial ischemia and may be a mediator of this process. Experimental data suggest that heparin may enhance this effect. The purpose of this open-labeled, placebo-controlled trial was to determine whether repeated intravenous administration of adenosine and heparin could mimic physiologic angiogenesis and reduce the amount of exercise-induced myocardial ischemia in patients with coronary artery disease. Subjects with chronic stable angina refractory to conventional medical therapy and not suitable for revascularization received either adenosine (140 microg/kg/min for 6 minutes) and heparin (10,000 U bolus), (n = 14), or placebo, (n = 7) daily for 10 days. All patients underwent baseline and follow-up exercise testing with thallium-201 single-photon emission computed tomography myocardial perfusion imaging. A semiquantitative assessment of the extent and severity of the perfusion abnormalities was calculated by 2 blinded investigators. There was no significant change in exercise duration or in the peak heart rate systolic blood pressure product associated with adenosine and heparin compared with placebo treatment. There was, however, a 9% reduction in the extent (60.6 +/- 4.0 vs 54.9 +/- 4.1, p = 0.03) and a 14% improvement in severity (41.5 +/- 3.2 vs 35.7 +/- 2.9, p = 0.01) of the myocardial perfusion abnormalities seen in patients who received adenosine and heparin compared with placebo. Thus, in this pilot study, repeated administration of adenosine and heparin reduced the amount of exercise-induced ischemia in patients with chronic stable angina refractory to conventional treatment.

Health of women after wartime deployments: correlates of risk for selected medical conditions among females after initial and repeat deployments to Afghanistan and Iraq, active component, U.S. Armed Forces.

PubMed

2012-07-01

Women account for approximately 10 percent of all U.S. military deployers to Afghanistan and Iraq. This analysis estimates the percentages of female deployers (n=154,548) who were affected by selected illnesses and injuries after first through third deployments to Iraq/Afghanistan in relation to age group, service branch, military occupation, marital status, pre-deployment medical history, "dwell time" prior to 2nd and 3rd deployments, and length of deployment. Of these factors, diagnosis of a condition before deployment was by far the strongest predictor of diagnosis of the condition after deployment. Durations of dwell times before repeat deployments were not strong predictors of post-deployment diagnoses of any of the conditions considered. For several conditions (e.g., PTSD, disorders of joints, peripheral enthesopathies, infertility), the percentages of deployers diagnosed with the conditions sharply increased with deployment length. Post-deployment morbidity moderately increased with increasing numbers of deployments in the case of some conditions (e.g., PTSD, migraine, musculoskeletal disorders), but not others. The findings suggest that limiting wartime deployments to nine months may have broad beneficial effects on the post-deployment health of female service members. However, limiting the number of wartime deployments and lengthening "dwell times" before repeat deployments would likely not have strong and broad beneficial effects on the health of female veterans. Further research to mitigate the effects of heavy loads and repetitive stresses on the musculoskeletal systems of combat deployed females is indicated.

METHOD OF PRODUCING U$sup 23$$sup 3$

DOEpatents

Seaborg, G.T.; Stoughton, R.W.

1960-08-30

A method for producing U/sup 233/ is outlined in which a body of thorium carbonate is heated to at least 200 deg C until it attains a constant weight and compressing the body into a pellet having a density of at least 2.6 g/cm/sup 3/. The pellet is enclosed in a sealed container and placed in the blanket of a thermal nuclear reactor having a neutron flux in which the majority of neutrons have an energy of below I Mev. The pellet is removed from the flux before the ratio of U/sup 233/ to Th/sup 232/ is about 1: 100.

Wongabel rhabdovirus accessory protein U3 targets the SWI/SNF chromatin remodeling complex.

PubMed

Joubert, D Albert; Rodriguez-Andres, Julio; Monaghan, Paul; Cummins, Michelle; McKinstry, William J; Paradkar, Prasad N; Moseley, Gregory W; Walker, Peter J

2015-01-15

Wongabel virus (WONV) is an arthropod-borne rhabdovirus that infects birds. It is one of the growing array of rhabdoviruses with complex genomes that encode multiple accessory proteins of unknown function. In addition to the five canonical rhabdovirus structural protein genes (N, P, M, G, and L), the 13.2-kb negative-sense single-stranded RNA (ssRNA) WONV genome contains five uncharacterized accessory genes, one overlapping the N gene (Nx or U4), three located between the P and M genes (U1 to U3), and a fifth one overlapping the G gene (Gx or U5). Here we show that WONV U3 is expressed during infection in insect and mammalian cells and is required for efficient viral replication. A yeast two-hybrid screen against a mosquito cell cDNA library identified that WONV U3 interacts with the 83-amino-acid (aa) C-terminal domain of SNF5, a component of the SWI/SNF chromatin remodeling complex. The interaction was confirmed by affinity chromatography, and nuclear colocalization was established by confocal microscopy. Gene expression studies showed that SNF5 transcripts are upregulated during infection of mosquito cells with WONV, as well as West Nile virus (Flaviviridae) and bovine ephemeral fever virus (Rhabdoviridae), and that SNF5 knockdown results in increased WONV replication. WONV U3 also inhibits SNF5-regulated expression of the cytokine gene CSF1. The data suggest that WONV U3 targets the SWI/SNF complex to block the host response to infection. The rhabdoviruses comprise a large family of RNA viruses infecting plants, vertebrates, and invertebrates. In addition to the major structural proteins (N, P, M, G, and L), many rhabdoviruses encode a diverse array of accessory proteins of largely unknown function. Understanding the role of these proteins may reveal much about host-pathogen interactions in infected cells. Here we examine accessory protein U3 of Wongabel virus, an arthropod-borne rhabdovirus that infects birds. We show that U3 enters the nucleus and interacts

Wongabel Rhabdovirus Accessory Protein U3 Targets the SWI/SNF Chromatin Remodeling Complex

PubMed Central

Joubert, D. Albert; Rodriguez-Andres, Julio; Monaghan, Paul; Cummins, Michelle; McKinstry, William J.; Paradkar, Prasad N.; Moseley, Gregory W.

2014-01-01

ABSTRACT Wongabel virus (WONV) is an arthropod-borne rhabdovirus that infects birds. It is one of the growing array of rhabdoviruses with complex genomes that encode multiple accessory proteins of unknown function. In addition to the five canonical rhabdovirus structural protein genes (N, P, M, G, and L), the 13.2-kb negative-sense single-stranded RNA (ssRNA) WONV genome contains five uncharacterized accessory genes, one overlapping the N gene (Nx or U4), three located between the P and M genes (U1 to U3), and a fifth one overlapping the G gene (Gx or U5). Here we show that WONV U3 is expressed during infection in insect and mammalian cells and is required for efficient viral replication. A yeast two-hybrid screen against a mosquito cell cDNA library identified that WONV U3 interacts with the 83-amino-acid (aa) C-terminal domain of SNF5, a component of the SWI/SNF chromatin remodeling complex. The interaction was confirmed by affinity chromatography, and nuclear colocalization was established by confocal microscopy. Gene expression studies showed that SNF5 transcripts are upregulated during infection of mosquito cells with WONV, as well as West Nile virus (Flaviviridae) and bovine ephemeral fever virus (Rhabdoviridae), and that SNF5 knockdown results in increased WONV replication. WONV U3 also inhibits SNF5-regulated expression of the cytokine gene CSF1. The data suggest that WONV U3 targets the SWI/SNF complex to block the host response to infection. IMPORTANCE The rhabdoviruses comprise a large family of RNA viruses infecting plants, vertebrates, and invertebrates. In addition to the major structural proteins (N, P, M, G, and L), many rhabdoviruses encode a diverse array of accessory proteins of largely unknown function. Understanding the role of these proteins may reveal much about host-pathogen interactions in infected cells. Here we examine accessory protein U3 of Wongabel virus, an arthropod-borne rhabdovirus that infects birds. We show that U3 enters the

Enhancer regions show high histone H3.3 turnover that changes during differentiation

PubMed Central

Deaton, Aimee M; Gómez-Rodríguez, Mariluz; Mieczkowski, Jakub; Tolstorukov, Michael Y; Kundu, Sharmistha; Sadreyev, Ruslan I; Jansen, Lars ET; Kingston, Robert E

2016-01-01

The organization of DNA into chromatin is dynamic; nucleosomes are frequently displaced to facilitate the ability of regulatory proteins to access specific DNA elements. To gain insight into nucleosome dynamics, and to follow how dynamics change during differentiation, we used a technique called time-ChIP to quantitatively assess histone H3.3 turnover genome-wide during differentiation of mouse ESCs. We found that, without prior assumptions, high turnover could be used to identify regions involved in gene regulation. High turnover was seen at enhancers, as observed previously, with particularly high turnover at super-enhancers. In contrast, regions associated with the repressive Polycomb-Group showed low turnover in ESCs. Turnover correlated with DNA accessibility. Upon differentiation, numerous changes in H3.3 turnover rates were observed, the majority of which occurred at enhancers. Thus, time-ChIP measurement of histone turnover shows that active enhancers are unusually dynamic in ESCs and changes in highly dynamic nucleosomes predominate at enhancers during differentiation. DOI: http://dx.doi.org/10.7554/eLife.15316.001 PMID:27304074

U 3Si 2 Fabrication and Testing for Implementation into the BISON Fuel Performance Code

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

Knight, Travis W.

A creep test stand was designed and constructed for compressive creep testing of U 3Si 2 pellets. This is described in Chapter 3. Creep testing of U 3Si 2 pellets was completed. In total, 13 compressive creep tests of U 3Si 2 pellets was successfully completed. This is reported in Chapter 3. Secondary creep model of U 3Si 2 was developed and implemented in BISON. This is described in Chapter 4. Properties of U 3Si 2 were implemented in BISON. This is described in Chapter 4. A resonant frequency and damping analyzer (RFDA) using impulse excitation technique (IET) was setup,more » tested, and used to analyze U 3Si 2 samples to measure Young’s and Shear Moduli which were then used to calculate the Poisson ratio for U 3Si 2. This is described in Chapter 5. Characterization of U 3Si 2 samples was completed. Samples were prepared and analyzed by XRD, SEM, and optical microscopy. Grain size analysis was conducted on images. SEM with EDS was used to analyze second phase precipitates. Impulse excitation technique was used to determine the Young’s and Shear Moduli of a tile specimen which allowed for the determination of the Poisson ratio. Helium pycnometry and mercury intrusion porosimetry was performed and used with image analysis to determine porosity size distribution. Vickers microindentation characterization method was used to evaluate the mechanical properties of U 3Si 2 including toughness, hardness, and Vickers hardness. Electrical resistivity measurement was done using the four-point probe method. This is reported in Chapter 5.« less

Somatic expansion behaviour of the (CTG)n repeat in myotonic dystrophy knock-in mice is differentially affected by Msh3 and Msh6 mismatch-repair proteins.

PubMed

van den Broek, Walther J A A; Nelen, Marcel R; Wansink, Derick G; Coerwinkel, Marga M; te Riele, Hein; Groenen, Patricia J T A; Wieringa, Bé

2002-01-15

The mechanism of expansion of the (CTG)n repeat in myotonic dystrophy (DM1) patients and the cause of its pathobiological effects are still largely unknown. Most likely, long repeats exert toxicity at the level of nuclear RNA transport or splicing. Here, we analyse cis- and trans-acting parameters that determine repeat behaviour in novel mouse models for DM1. Our mice carry 'humanized' myotonic dystrophy protein kinase (Dmpk) allele(s) with either a (CTG)84 or a (CTG)11 repeat, inserted at the correct position into the endogenous DM locus. Unlike in the human situation, the (CTG)84 repeat in the syntenic mouse environment was relatively stable during intergenerational segregation. However, somatic tissues showed substantial repeat expansions which were progressive upon aging and prominent in kidney, and in stomach and small intestine, where it was cell-type restricted. Other tissues examined showed only marginal size changes. The (CTG)11 allele was completely stable, as anticipated. Introducing the (CTG)84 allele into an Msh3-deficient background completely blocked the somatic repeat instability. In contrast, Msh6 deficiency resulted in a significant increase in the frequency of somatic expansions. Competition of Msh3 and Msh6 for binding to Msh2 in functional complexes with different DNA mismatch-recognition specificity may explain why the somatic (CTG)n expansion rate is differentially affected by ablation of Msh3 and Msh6.

Repeated chlorpromazine administration increases a behavioural response of rats to 5-hydroxytryptamine receptor stimulation.

PubMed Central

Green, A R

1977-01-01

1 The hyperactivity syndrome produced in rats by administration of tranylcypromine (20 mg/kg i.p.) followed 30 min later by L-tryptophan (50 mg/kg i.p.) is generally considered to be due to increased 5-hydroxytryptamine (5-HT) functional activity. It is inhibited by chlorpromazine (30 mg/kg i.p.) injected 60 min before the tranylcypromine. However, chlorpromazine injection for 4 days either at a dose of 30 mg/kg once daily or 5 mg/kg twice daily results in an enhanced hyperactivity response to tranylcypromine and L-tryptophan administration 24 h after the final dose of chlorpromazine. 2 One injection of chlorpromazine (30 mg/kg) did not produce enhancement 24 h later and the inhibition of the tranylcypromine/L-tryptophan hyperactivity observed after acute chlorpromazine injection was seen if the rats were given tranylcypromine and L-tryptophan 1 h after the fourth chlorpromazine (30 mg/kg) dose. 3 Chlorpromazine (30 mg/kg) once daily or 5 mg/kg twice daily for 4 days resulted in rats displaying enhanced behavioral responses to the suggested 5-HT agonist 5-methoxy N,N-dimethyltryptamine (2 mg/kg) on day 5. 4 Chlorpromazine (30 mg/kg) once daily for 4 days produces a slight increase in brain 5-hydroxytryptamine (5-HT) concentration on day 5, but no difference in the rate of brain 5-HT synthesis or the rate of 5-HT accumulation after tranylcypromine and L-tryptophan administration. 5. There is some evidence that chlorpromazine blocks 5-HT receptors. It has also been observed that several other neuroleptic drugs do not produce enhanced 5-HT responses after repeated administration. It is suggested therefore that the enhanced behavioural response to 5-HT receptor stimulation following repeated chlorpromazine administration may be because this drug blocks 5-HT receptors. PMID:264797

Enhancer Evolution across 20 Mammalian Species

PubMed Central

Villar, Diego; Berthelot, Camille; Aldridge, Sarah; Rayner, Tim F.; Lukk, Margus; Pignatelli, Miguel; Park, Thomas J.; Deaville, Robert; Erichsen, Jonathan T.; Jasinska, Anna J.; Turner, James M.A.; Bertelsen, Mads F.; Murchison, Elizabeth P.; Flicek, Paul; Odom, Duncan T.

2015-01-01

Summary The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution. PMID:25635462

Early versus late GD-DTPA MRI enhancement in experimental glioblastomas.

PubMed

Farace, Paolo; Tambalo, Stefano; Fiorini, Silvia; Merigo, Flavia; Daducci, Alessandro; Nicolato, Elena; Conti, Giamaica; Degrassi, Anna; Sbarbati, Andrea; Marzola, Pasquina

2011-03-01

To compare early versus late enhancement in two glioblastoma models characterized by different infiltrative/edematous patterns. Three weeks after inoculation into nude mice of U87MG and U251 cells, T1-weighted images were acquired early (10.5 min), intermediate (21 min) and late (30.5 min) after a bolus injection of Gd-DTPA at 300 μ mol/kg dosage. EARLY(TH) and LATE(TH) were the corresponding volumes with an enhancement higher than a threshold TH, defined by the mean (μ) and standard deviation (σ) on a contralateral healthy area. ADD(TH) was the enhancing volume found in LATE(TH) but not in EARLY(TH). T2 imaging of both tumors was performed, and T2 mapping of U251. In all tumors, LATE(TH) was significantly higher than EARLY(TH) for TH ranging from μ+σ to μ+5σ. The ADD(TH) /EARLY(TH) ratio was not significantly different when U251 and U87MG tumors were compared. In the U87MG tumors, some enhancement was observed outside the regularly demarcated T2-hyperintense area. In the U251 tumors, irregularly T2 demarcated, a large portion of ADD(μ+3σ) had normal T2 values. At histology, U251 showed a higher infiltrative pattern than U87MG. In these models, the increase over time in the enhancing volume did not depend on the different infiltrative/edematous patterns and was not closely related with edema. Copyright © 2011 Wiley-Liss, Inc.

ATXN2 trinucleotide repeat length correlates with risk of ALS.

PubMed

Sproviero, William; Shatunov, Aleksey; Stahl, Daniel; Shoai, Maryam; van Rheenen, Wouter; Jones, Ashley R; Al-Sarraj, Safa; Andersen, Peter M; Bonini, Nancy M; Conforti, Francesca L; Van Damme, Philip; Daoud, Hussein; Del Mar Amador, Maria; Fogh, Isabella; Forzan, Monica; Gaastra, Ben; Gellera, Cinzia; Gitler, Aaron D; Hardy, John; Fratta, Pietro; La Bella, Vincenzo; Le Ber, Isabelle; Van Langenhove, Tim; Lattante, Serena; Lee, Yi-Chung; Malaspina, Andrea; Meininger, Vincent; Millecamps, Stéphanie; Orrell, Richard; Rademakers, Rosa; Robberecht, Wim; Rouleau, Guy; Ross, Owen A; Salachas, Francois; Sidle, Katie; Smith, Bradley N; Soong, Bing-Wen; Sorarù, Gianni; Stevanin, Giovanni; Kabashi, Edor; Troakes, Claire; van Broeckhoven, Christine; Veldink, Jan H; van den Berg, Leonard H; Shaw, Christopher E; Powell, John F; Al-Chalabi, Ammar

2017-03-01

We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10 -18 ), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R 2  = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Strategy When Faced with Failure: Persistence and Degree Attainment of Course Repeaters versus Non-Repeaters. AIR 2002 Forum Paper.

ERIC Educational Resources Information Center

Fenton, Kathleen S.

Graduation and persistence rates were compared for 184 students, 92 of whom had repeated multiple courses or at least 1 course 3 times. A control group of 92 nonrepeating students was drawn from the remaining 303 students of the entire 1996 cohort. There was no difference between the graduation rate of repeaters and nonrepeaters. The persistence…

IFIT3 and IFIT2/3 promote IFIT1-mediated translation inhibition by enhancing binding to non-self RNA.

PubMed

Fleith, Renata C; Mears, Harriet V; Leong, Xin Yun; Sanford, Thomas J; Emmott, Edward; Graham, Stephen C; Mansur, Daniel S; Sweeney, Trevor R

2018-06-01

Interferon-induced proteins with tetratricopeptide repeats (IFITs) are highly expressed during the cell-intrinsic immune response to viral infection. IFIT1 inhibits translation by binding directly to the 5' end of foreign RNAs, particularly those with non-self cap structures, precluding the recruitment of the cap-binding eukaryotic translation initiation factor 4F and ribosome recruitment. The presence of IFIT1 imposes a requirement on viruses that replicate in the cytoplasm to maintain mechanisms to avoid its restrictive effects. Interaction of different IFIT family members is well described, but little is known of the molecular basis of IFIT association or its impact on function. Here, we reconstituted different complexes of IFIT1, IFIT2 and IFIT3 in vitro, which enabled us to reveal critical aspects of IFIT complex assembly. IFIT1 and IFIT3 interact via a YxxxL motif present in the C-terminus of each protein. IFIT2 and IFIT3 homodimers dissociate to form a more stable heterodimer that also associates with IFIT1. We show for the first time that IFIT3 stabilizes IFIT1 protein expression, promotes IFIT1 binding to a cap0 Zika virus reporter mRNA and enhances IFIT1 translation inhibition. This work reveals molecular aspects of IFIT interaction and provides an important missing link between IFIT assembly and function.

YeeU enhances the bundling of cytoskeletal polymers of MreB and FtsZ, antagonizing the CbtA (YeeV) toxicity in Escherichia coli.

PubMed

Masuda, Hisako; Tan, Qian; Awano, Naoki; Wu, Kuen-Phon; Inouye, Masayori

2012-06-01

All free-living bacteria carry the toxin-antitoxin (TA) systems controlling cell growth and death under stress conditions. YeeU-YeeV (CbtA) is one of the Escherichia coli TA systems, and the toxin, CbtA, has been reported to inhibit the polymerization of bacterial cytoskeletal proteins, MreB and FtsZ. Here, we demonstrate that the antitoxin, YeeU, is a novel type of antitoxin (type IV TA system), which does not form a complex with CbtA but functions as an antagonist for CbtA toxicity. Specifically, YeeU was found to directly interact with MreB and FtsZ, and enhance the bundling of their filamentous polymers in vitro. Surprisingly, YeeU neutralized not only the toxicity of CbtA but also the toxicity caused by other inhibitors of MreB and FtsZ, such as A22, SulA and MinC, indicating that YeeU-induced bundling of MreB and FtsZ has an intrinsic global stabilizing effect on their homeostasis. Here we propose to rename YeeU as CbeA for cytoskeleton bundling-enhancing factor A. © 2012 Blackwell Publishing Ltd.

Repeated onabotulinumtoxin-a injections provide better results than single injection in treatment of painful bladder syndrome.

PubMed

Kuo, Hann-Chorng

2013-01-01

Onabotulinumtoxin-A (BoNT-A) is effective for the treatment of interstitial cystitis/painful bladder syndrome (IC/PBS). However, long-term follow-up does not show successful outcome after a single injection. To evaluate the efficacy and safety of repeated intravesical BoNT-A injections for treatment of IC/PBS and compare the success rates among patient groups receiving different injection numbers. Prospective interventional study. Tertiary medical center. Intravesical injection of 100 U of BoNT-A was performed in 81 patients every 6 months for up to 4 times or until patients' symptoms significantly improved. Patients who received a single injection served as active controls. Measured parameters included O'Leary-Sant symptom indexes (ICSI) and problem indexes (ICPI), visual analogue score (VAS) for pain, voiding diary variables, urodynamic parameters, maximal bladder capacity under anesthesia, glomerulation grade, and global response assessment. Multiple measurements and Kaplan-Meier analysis were used for comparison of consecutive data and success rates among groups. Among 81 patients, 20 received single injections, 19 received 2 injections, 12 received 3 injections, and 30 received 4 injections. The mean (± standard deviation) of ICSI, ICPI, total scores, VAS, functional bladder capacity, and daytime frequency all showed significant improvement after repeated BoNT-A treatment with different injections. Significantly better success rates were noted in patients who received 4 repeated injections (P = 0.0242) and 3 injections (P = 0.050), compared to those who received a single injection. However, there was no significant difference of long-term success rates among patients who received 2, 3, and 4 injections. Lack of placebo control group is the main limitation. Repeated intravesical BoNT-A injections were safe and effective for pain relief and they increased bladder capacity and provided a better long-term success rate than a single injection did for treatment of

To Repeat or Not to Repeat a Course

ERIC Educational Resources Information Center

Armstrong, Michael J.; Biktimirov, Ernest N.

2013-01-01

The difficult transition from high school to university means that many students need to repeat (retake) 1 or more of their university courses. The authors examine the performance of students repeating first-year core courses in an undergraduate business program. They used data from university records for 116 students who took a total of 232…

Safety Validation of Repeated Blood-Brain Barrier Disruption Using Focused Ultrasound.

PubMed

Kobus, Thiele; Vykhodtseva, Natalia; Pilatou, Magdalini; Zhang, Yongzhi; McDannold, Nathan

2016-02-01

The purpose of this study was to investigate the effects on the brain of multiple sessions of blood-brain barrier (BBB) disruption using focused ultrasound (FUS) in combination with micro-bubbles over a range of acoustic exposure levels. Six weekly sessions of FUS, using acoustical pressures between 0.66 and 0.80 MPa, were performed under magnetic resonance guidance. The success and degree of BBB disruption was estimated by signal enhancement of post-contrast T1-weighted imaging of the treated area. Histopathological analysis was performed after the last treatment. The consequences of repeated BBB disruption varied from no indications of vascular damage to signs of micro-hemorrhages, macrophage infiltration, micro-scar formations and cystic cavities. The signal enhancement on the contrast-enhanced T1-weighted imaging had limited value for predicting small-vessel damage. T2-weighted imaging corresponded well with the effects on histopathology and could be used to study treatment effects over time. This study demonstrates that repeated BBB disruption by FUS can be performed with no or limited damage to the brain tissue. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Viral delivery of C9orf72 hexanucleotide repeat expansions in mice leads to repeat-length-dependent neuropathology and behavioural deficits

PubMed Central

Herranz-Martin, Saul; Lewis, Katherine; Mulcahy, Padraig; Higginbottom, Adrian; Walker, Callum; Valenzuela, Isabel Martinez-Pena y; Coldicott, Ian; Shaw, Pamela J.

2017-01-01

ABSTRACT Intronic GGGGCC repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Two major pathologies stemming from the hexanucleotide RNA expansions (HREs) have been identified in postmortem tissue: intracellular RNA foci and repeat-associated non-ATG dependent (RAN) dipeptides, although it is unclear how these and other hallmarks of disease contribute to the pathophysiology of neuronal injury. Here, we describe two novel lines of mice that overexpress either 10 pure or 102 interrupted GGGGCC repeats mediated by adeno-associated virus (AAV) and recapitulate the relevant human pathology and disease-related behavioural phenotypes. Similar levels of intracellular RNA foci developed in both lines of mice, but only mice expressing 102 repeats generated C9orf72 RAN pathology, neuromuscular junction (NMJ) abnormalities, dispersal of the hippocampal CA1, enhanced apoptosis, and deficits in gait and cognition. Neither line of mice, however, showed extensive TAR DNA-binding protein 43 (TDP-43) pathology or neurodegeneration. Our data suggest that RNA foci pathology is not a good predictor of C9orf72 RAN dipeptide formation, and that RAN dipeptides and NMJ dysfunction are drivers of C9orf72 disease pathogenesis. These AAV-mediated models of C9orf72-associated ALS/FTD will be useful tools for studying disease pathophysiology and developing new therapeutic approaches. PMID:28550099

Enhanced scintillation of Ba3In(B3O6)3 based on nitrogen doping

NASA Astrophysics Data System (ADS)

Wang, Z. X.; Pei, H.; Tao, X. M.; Cai, G. M.; Mao, R. H.; Jin, Z. P.

2018-02-01

Scintillating materials, as a class of luminescent materials, are highly demanded for practical use in the high-energy detection. However, the applications are often hampered by their low light yield (LY) or long decay time for many traditional scintillators. In this work, upon nitrogen anion doping, scintillation performance in layered borate Ba3In(B3O6)3 (BIB) has been excellently enhanced with high XEL intensity of ～3 times as large as that of commercial Bi4Ge3O12 (BGO) and ultra-fast fluorescent decay time of ～1.25 ns. To shed light on origins of the intrinsic violet-blue emission, we measured the in-situ vacuum ultraviolet excited (VUV) emission spectra of N-BIB ceramic. Combined with experiments and first principles calculations, the band-gap reduction and donor-acceptor density increasing by nitrogen (N) doping is responsible for the enhancement of scintillation performance for N-doped Ba3In(B3O6)3. Moreover, nitrogen anion doping rather than conventional cation doping is found to be also applicable to other intrinsic luminescent materials for enhancing performance.

Dental Student Academic Integrity in U.S. Dental Schools: Current Status and Recommendations for Enhancement.

PubMed

Graham, Bruce S; Knight, G William; Graham, Linda

2016-01-01

Cheating incidents in 2006-07 led U.S. dental schools to heighten their efforts to enhance the environment of academic integrity in their institutions. The aims of this study were to document the measures being used by U.S. dental schools to discourage student cheating, determine the current incidence of reported cheating, and make recommendations for enhancing a culture of integrity in dental education. In late 2014-early 2015, an online survey was distributed to academic deans of all 61 accredited U.S. dental schools that had four classes of dental students enrolled; 50 (82%) responded. Among measures used, 98% of respondents reported having policy statements regarding student academic integrity, 92% had an Honor Code, 96% provided student orientation to integrity policies, and most used proctoring of final exams (91%) and tests (93%). Regarding disciplinary processes, 27% reported their faculty members only rarely reported suspected cheating (though required in 76% of the schools), and 40% disseminated anonymous results of disciplinary hearings. A smaller number of schools (n=36) responded to the question about student cheating than to other questions; those results suggested that reported cheating had increased almost threefold since 1998. The authors recommend that schools add cheating case scenarios to professional ethics curricula; disseminate outcomes of cheating enforcement actions; have students sign a statement attesting to compliance with academic integrity policies at every testing activity; add curricular content on correct writing techniques to avoid plagiarism; require faculty to distribute retired test items; acquire examination-authoring software programs to enable faculty to generate new multiple-choice items and different versions of the same multiple-choice tests; avoid take-home exams when assessing independent student knowledge; and utilize student assessment methods directly relevant to clinical practice.

Enhanced Historical Land-Use and Land-Cover Data Sets of the U.S. Geological Survey

USGS Publications Warehouse

Price, Curtis V.; Nakagaki, Naomi; Hitt, Kerie J.; Clawges, Rick M.

2007-01-01

Historical land-use and land-cover data, available from the U.S. Geological Survey (USGS) for the conterminous United States and Hawaii, have been enhanced for use in geographic information systems (GIS) applications. The original digital data sets were created by the USGS in the late 1970s and early 1980s and were later converted by USGS and the U.S. Environmental Protection Agency (USEPA) to a geographic information system (GIS) format in the early 1990s. These data were made available on USEPA's Web site since the early 1990s and have been used for many national applications, despite minor coding and topological errors. During the 1990s, a group of USGS researchers made modifications to the data set for use in the National Water-Quality Assessment Program. These edited files have been further modified to create a more accurate, topologically clean, and seamless national data set. Several different methods, including custom editing software and several batch processes, were applied to create this enhanced version of the national data set. The data sets are included in this report in the commonly used shapefile and Tagged Image Format File (TIFF) formats. In addition, this report includes two polygon data sets (in shapefile format) representing (1) land-use and land-cover source documentation extracted from the previously published USGS data files, and (2) the extent of each polygon data file.

First-principles study of low-spin LaCoO3 with structurally consistent Hubbard U

NASA Astrophysics Data System (ADS)

Hsu, H.; Umemoto, K.; Cococcioni, M.; Wentzcovitch, R.

2008-12-01

We use the local density approximation + Hubbard U (LDA+U) method to calculate the structural and electronic properties of low-spin LaCoO3. The Hubbard U is obtained by first principles and consistent with each fully-optimized atomic structure at different pressures. With structurally consistent U, the fully-optimized atomic structure agrees with experimental data better than the calculations with fixed or vanishing U. A discussion on how the Hubbard U affects the electronic and atomic structure of LaCoO3 is also given.

The open reading frames in the 3' long terminal repeats of several mouse mammary tumor virus integrants encode V beta 3-specific superantigens

PubMed Central

1992-01-01

Mice expressing the minor lymphocyte stimulation antigens, Mls-1a, -2a, or -3a, singly on the B10.BR background have been generated. Mls phenotypes correlate with the integration of mouse mammary tumor viruses (MTV) in the mouse genome. The open reading frames within the 3' long terminal repeats of the integrated MTVs 1, 3, 6, and 13 encode V beta 3-specific superantigens. Sequence data for these viral superantigens is presented, indicating that it is the COOH-terminal portion of the viral superantigen that interacts with the T cell receptor V beta element. PMID:1309854

The influence of repeated abutment changes on peri-implant tissue stability: 3-year post-loading results from a multicentre randomised controlled trial.

PubMed

Bressan, Eriberto; Grusovin, Maria Gabriella; D'Avenia, Ferdinando; Neumann, Konrad; Sbricoli, Luca; Luongo, Giuseppe; Esposito, Marco

To evaluate the influence of at least three abutment disconnections in conventional loaded implants against placement of a definitive abutment in immediately non-occlusal loaded implants on hard and soft tissue changes. A secondary aim was to evaluate whether the presence of less than 2 mm of keratinised mucosa is associated with increased peri-implant marginal bone loss and soft tissue recessions. Eighty patients requiring one single crown or one fixed partial prosthesis supported by a maximum of three implants were randomised, after implants were placed with more than 35 Ncm, according to a parallel group design to receive definitive abutments that were loaded immediately (definitive abutment or immediate loading group) or transmucosal abutments, which were delayed loaded after 3 months and removed at least three times: 1. At impression taking (3 months after implant placement); 2. When checking the zirconium core on titanium abutments at single crowns or the fitting the metal structure at prostheses supported by multiple implants; 3. At delivery of the definitive prostheses (repeated disconnection or conventional loading group). Patients were treated at four centres and each patient contributed to the study, with only one prosthesis followed for 3 years after initial loading. Outcome measures were: prosthesis failures, implant failures, complications, pink aesthetic score (PES), buccal recessions, patient satisfaction, peri-implant marginal bone level changes and height of the keratinised mucosa. Forty patients were randomly allocated to each group according to a parallel group design. Six patients from the definitive abutment group dropped out or died, and one left from the repeated disconnection group. One implant, from the repeated disconnection group, fractured (difference = 3%; CI 95%: -2%, 8%; P = 1). Four provisional crowns and one definitive single crown had to be remade because of poor fitting, and one definitive crown and one definitive prosthesis

Repeat surfactant therapy for postsurfactant slump.

PubMed

Katz, L A; Klein, J M

2006-07-01

To evaluate repeat surfactant therapy for the treatment of respiratory failure associated with postsurfactant slump in extremely low birth weight infants (ELBW) by characterizing the population of premature infants who develop postsurfactant slump and measuring their response to a secondary course of surfactant therapy. A retrospective analysis of a cohort of all patients admitted over a 3-year period with birth weights <1000 g (ELBW infants). Information was collected by chart review and the patients were categorized into three distinct groups for analysis. Initial surfactant only, patients who received surfactant replacement therapy only for respiratory distress syndrome (RDS); repeat surfactant, patients who received both initial surfactant replacement for RDS and repeat surfactant therapy for postsurfactant slump (defined as respiratory failure after 6 days of age), and no surfactant, patients in whom no surfactant was ever administered. A respiratory severity score (RSS) was used to measure the severity of lung disease and response to surfactant therapy. Over 3 years, there were 165 ELBW infants who could develop postsurfactant slump and be eligible for repeat surfactant therapy. There were 39 infants who never received any surfactant therapy estimated gestational age (EGA) 27.7 +/- 1.7, birth weight 856 +/- 109 g) either at birth or after 6 days of life. There were 126 patients treated for RDS with initial surfactant replacement therapy (EGA 25.6 +/- 1.9 weeks, birth weight 713 +/- 179 g). Out of these RDS patients, 101 improved with an initial course of surfactant therapy (EGA 26 +/- 1.8, birth weight 751 +/- 143 g), but 25 (20% of the patients with RDS) developed postsurfactant slump and received a repeat course of surfactant therapy (EGA 24.7 +/- 1.2, birth weight 647 +/- 120 g). The repeat surfactant group (postsurfactant slump) was significantly more premature and had significantly lower birth weights compared to both the initial surfactant only group

SAHA-induced TRAIL-sensitisation of Multiple Myeloma cells is enhanced in 3D cell culture.

PubMed

Arhoma, A; Chantry, A D; Haywood-Small, S L; Cross, N A

2017-11-15

Multiple Myeloma (MM) is currently incurable despite many novel therapies. Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) is a potential anti-tumour agent although effects as a single agent are limited. In this study, we investigated whether the Histone Deacetylase (HDAC) inhibitor SAHA can enhance TRAIL-induced apoptosis and target TRAIL resistance in both suspension culture, and 3D cell culture as a model of disseminated MM lesions that form in bone. The effects of SAHA and/or TRAIL in 6 Multiple Myeloma cell lines were assessed in both suspension cultures and in an Alginate-based 3D cell culture model. The effect of SAHA and/or TRAIL was assessed on apoptosis by assessment of nuclear morphology using Hoechst 33342/Propidium Iodide staining. Viable cell number was assessed by CellTiter-Glo luminescence assay, Caspase-8 and -9 activities were measured by Caspase-Glo™ assay kit. TRAIL-resistant cells were generated by culture of RPMI 8226 and NCI-H929 by acute exposure to TRAIL followed by selection of TRAIL-resistant cells. TRAIL significantly induced apoptosis in a dose-dependent manner in OPM-2, RPMI 8226, NCI-H929, U266, JJN-3 MM cell lines and ADC-1 plasma cell leukaemia cells. SAHA amplified TRAIL responses in all lines except OPM-2, and enhanced TRAIL responses were both via Caspase-8 and -9. SAHA treatment induced growth inhibition that further increased in the combination treatment with TRAIL in MM cells. The co-treatment of TRAIL and SAHA reduced viable cell numbers all cell lines. TRAIL responses were further potentiated by SAHA in 3D cell culture in NCI-H929, RPMI 8226 and U266 at lower TRAIL + SAHA doses than in suspension culture. However TRAIL responses in cells that had been selected for TRAIL resistance were not further enhanced by SAHA treatment. SAHA is a potent sensitizer of TRAIL responses in both TRAIL sensitive and resistant cell lines, in both suspension and 3D culture, however SAHA did not sensitise TRAIL-sensitive cell

N-acetylcysteine enhances endothelium-dependent vasorelaxation in the isolated rat mesenteric artery.

PubMed

Lopez, B L; Snyder, J W; Birenbaum, D S; Ma, X I

1998-10-01

Previous studies have suggested that N-acetylcysteine (NAC) may confer additional protection in acetaminophen (APAP) overdose by improving hepatic microcirculation. We hypothesize that NAC enhances release of nitric oxide (NO) from the vasculature. Sprague-Dawley rat superior mesenteric artery rings were suspended in oxygenated Krebs-Henseleit tissue baths and contracted with U-46619 (a thromboxane A2-mimetic). In part 1, the effect of NAC on endothelial cell (EC) release of NO was assessed by measurement of vasorelaxation induced by acetylcholine (ACh, an EC-dependent vasorelaxor) in the presence and absence of NAC. In part 2, the effect of glutathione (a major component of NAC hepatoprotection) was examined by measuring ACh-induced vasorelaxation in rings from rats treated with L-buthionine sulfoxamine (BSO, a glutathione synthesis inhibitor). Data were analyzed by repeated-measures ANOVA. Addition of 15 to 30 mmol/L NAC after ring contraction had no direct vasodilatory effect. By contrast, pretreatment of rings with NAC (15 mmol/L) enhanced vasorelaxation induced by ACh (95.0% +/- 7.9% versus 62.3% +/- 7.6% for control; ACh dose, 1 mumol/L; P < .001) or by A23187, a receptor-independent, NO-mediated vasodilator (91.6% +/- 9.6% versus 68.3% +/- 12.1% for control; A23187 dose, 1 mumol/L; P < .001). In rings from BSO-treated rats, NAC also enhanced vasorelaxation (76.5% +/- 7.1%; P < .001 versus control), but to a lesser degree than in nontreated rats. NAC enhances endothelium-dependent vasodilation in an isolated rat mesenteric artery ring preparation. In addition to its antioxidant effects, NAC may decrease APAP hepatotoxicity by stimulating NO production and improving microvascular circulation.

Conserved structure and inferred evolutionary history of long terminal repeats (LTRs)

PubMed Central

2013-01-01

Background Long terminal repeats (LTRs, consisting of U3-R-U5 portions) are important elements of retroviruses and related retrotransposons. They are difficult to analyse due to their variability. The aim was to obtain a more comprehensive view of structure, diversity and phylogeny of LTRs than hitherto possible. Results Hidden Markov models (HMM) were created for 11 clades of LTRs belonging to Retroviridae (class III retroviruses), animal Metaviridae (Gypsy/Ty3) elements and plant Pseudoviridae (Copia/Ty1) elements, complementing our work with Orthoretrovirus HMMs. The great variation in LTR length of plant Metaviridae and the few divergent animal Pseudoviridae prevented building HMMs from both of these groups. Animal Metaviridae LTRs had the same conserved motifs as retroviral LTRs, confirming that the two groups are closely related. The conserved motifs were the short inverted repeats (SIRs), integrase recognition signals (5´TGTTRNR…YNYAACA 3´); the polyadenylation signal or AATAAA motif; a GT-rich stretch downstream of the polyadenylation signal; and a less conserved AT-rich stretch corresponding to the core promoter element, the TATA box. Plant Pseudoviridae LTRs differed slightly in having a conserved TATA-box, TATATA, but no conserved polyadenylation signal, plus a much shorter R region. The sensitivity of the HMMs for detection in genomic sequences was around 50% for most models, at a relatively high specificity, suitable for genome screening. The HMMs yielded consensus sequences, which were aligned by creating an HMM model (a ‘Superviterbi’ alignment). This yielded a phylogenetic tree that was compared with a Pol-based tree. Both LTR and Pol trees supported monophyly of retroviruses. In both, Pseudoviridae was ancestral to all other LTR retrotransposons. However, the LTR trees showed the chromovirus portion of Metaviridae clustering together with Pseudoviridae, dividing Metaviridae into two portions with distinct phylogeny. Conclusion The HMMs

Can the Palatability of Healthy, Satiety-Promoting Foods Increase with Repeated Exposure during Weight Loss?

PubMed Central

Anguah, Katherene O.-B.; Lovejoy, Jennifer C.; Craig, Bruce A.; Gehrke, Malinda M.; Palmer, Philip A.; Eichelsdoerfer, Petra E.; McCrory, Megan A.

2017-01-01

Repeated exposure to sugary, fatty, and salty foods often enhances their appeal. However, it is unknown if exposure influences learned palatability of foods typically promoted as part of a healthy diet. We tested whether the palatability of pulse containing foods provided during a weight loss intervention which were particularly high in fiber and low in energy density would increase with repeated exposure. At weeks 0, 3, and 6, participants (n = 42; body mass index (BMI) 31.2 ± 4.3 kg/m2) were given a test battery of 28 foods, approximately half which had been provided as part of the intervention, while the remaining half were not foods provided as part of the intervention. In addition, about half of each of the foods (provided as part or not provided as part of the intervention) contained pulses. Participants rated the taste, appearance, odor, and texture pleasantness of each food, and an overall flavor pleasantness score was calculated as the mean of these four scores. Linear mixed model analyses showed an exposure type by week interaction effect for taste, texture and overall flavor pleasantness indicating statistically significant increases in ratings of provided foods in taste and texture from weeks 0 to 3 and 0 to 6, and overall flavor from weeks 0 to 6. Repeated exposure to these foods, whether they contained pulses or not, resulted in a ~4% increase in pleasantness ratings. The long-term clinical relevance of this small increase requires further study. PMID:28231094

Identification of an osteoclast transcription factor that binds to the human T cell leukemia virus type I-long terminal repeat enhancer element.

PubMed

Inoue, D; Santiago, P; Horne, W C; Baron, R

1997-10-03

Transgenic mice expressing human T cell leukemia virus type I (HTLV-I)-tax under the control of HTLV-I-long terminal repeat (LTR) promoter develop skeletal abnormalities with high bone turnover and myelofibrosis. In these animals, Tax is highly expressed in bone with a pattern of expression restricted to osteoclasts and spindle-shaped cells within the endosteal myelofibrosis. To test the hypothesis that lineage-specific transcription factors promote transgene expression from the HTLV-I-LTR in osteoclasts, we first examined tax expression in transgenic bone marrow cultures. Expression was dependent on 1alpha,25-dihydroxycholecalciferol and coincided with tartrate-resistant acid phosphatase (TRAP) expression, a marker of osteoclast differentiation. Furthermore, Tax was expressed in vitronectin receptor-positive mononuclear precursors as well as in mature osteoclast-like cells (OCLs). Consistent with our hypothesis, electrophoretic mobility shift assays revealed the presence of an OCL nuclear factor (NFOC-1) that binds to the LTR 21-base pair direct repeat, a region critical for the promoter activity. This binding is further enhanced by Tax. Since NFOC-1 is absent in macrophages and conserved in osteoclasts among species including human, such a factor may play a role in lineage determination and/or in expression of the differentiated osteoclast phenotype.

Repeating and non-repeating fast radio bursts from binary neutron star mergers

NASA Astrophysics Data System (ADS)

Yamasaki, Shotaro; Totani, Tomonori; Kiuchi, Kenta

2018-04-01

Most fast radio bursts (FRB) do not show evidence of repetition, and such non-repeating FRBs may be produced at the time of a merger of binary neutron stars (BNS), provided that the BNS merger rate is close to the high end of the currently possible range. However, the merger environment is polluted by dynamical ejecta, which may prohibit the radio signal from propagating. We examine this by using a general-relativistic simulation of a BNS merger, and show that the ejecta appears about 1 ms after the rotation speed of the merged star becomes the maximum. Therefore there is a time window in which an FRB signal can reach outside, and the short duration of non-repeating FRBs can be explained by screening after ejecta formation. A fraction of BNS mergers may leave a rapidly rotating and stable neutron star, and such objects may be the origin of repeating FRBs like FRB 121102. We show that a merger remnant would appear as a repeating FRB on a time scale of ˜1-10 yr, and expected properties are consistent with the observations of FRB 121102. We construct an FRB rate evolution model that includes these two populations of repeating and non-repeating FRBs from BNS mergers, and show that the detection rate of repeating FRBs relative to non-repeating ones rapidly increases with improving search sensitivity. This may explain why only the repeating FRB 121102 was discovered by the most sensitive FRB search with Arecibo. Several predictions are made, including the appearance of a repeating FRB 1-10 yr after a BNS merger that is localized by gravitational waves and subsequent electromagnetic radiation.

Repeating and non-repeating fast radio bursts from binary neutron star mergers

NASA Astrophysics Data System (ADS)

Yamasaki, Shotaro; Totani, Tomonori; Kiuchi, Kenta

2018-06-01

Most fast radio bursts (FRB) do not show evidence of repetition, and such non-repeating FRBs may be produced at the time of a merger of binary neutron stars (BNS), provided that the BNS merger rate is close to the high end of the currently possible range. However, the merger environment is polluted by dynamical ejecta, which may prohibit the radio signal from propagating. We examine this by using a general-relativistic simulation of a BNS merger, and show that the ejecta appears about 1 ms after the rotation speed of the merged star becomes the maximum. Therefore there is a time window in which an FRB signal can reach outside, and the short duration of non-repeating FRBs can be explained by screening after ejecta formation. A fraction of BNS mergers may leave a rapidly rotating and stable neutron star, and such objects may be the origin of repeating FRBs like FRB 121102. We show that a merger remnant would appear as a repeating FRB on a time scale of ˜1-10 yr, and expected properties are consistent with the observations of FRB 121102. We construct an FRB rate evolution model that includes these two populations of repeating and non-repeating FRBs from BNS mergers, and show that the detection rate of repeating FRBs relative to non-repeating ones rapidly increases with improving search sensitivity. This may explain why only the repeating FRB 121102 was discovered by the most sensitive FRB search with Arecibo. Several predictions are made, including the appearance of a repeating FRB 1-10 yr after a BNS merger that is localized by gravitational waves and subsequent electromagnetic radiation.

Repeated annual influenza vaccination and vaccine effectiveness: review of evidence.

PubMed

Belongia, Edward A; Skowronski, Danuta M; McLean, Huong Q; Chambers, Catharine; Sundaram, Maria E; De Serres, Gaston

2017-07-01

Studies in the 1970s and 1980s signaled concern that repeated influenza vaccination could affect vaccine protection. The antigenic distance hypothesis provided a theoretical framework to explain variability in repeat vaccination effects based on antigenic similarity between successive vaccine components and the epidemic strain. Areas covered: A meta-analysis of vaccine effectiveness studies from 2010-11 through 2014-15 shows substantial heterogeneity in repeat vaccination effects within and between seasons and subtypes. When negative effects were observed, they were most pronounced for H3N2, especially in 2014-15 when vaccine components were unchanged and antigenically distinct from the epidemic strain. Studies of repeated vaccination across multiple seasons suggest that vaccine effectiveness may be influenced by more than one prior season. In immunogenicity studies, repeated vaccination blunts the hemagglutinin antibody response, particularly for H3N2. Expert commentary: Substantial heterogeneity in repeated vaccination effects is not surprising given the variation in study populations and seasons, and the variable effects of antigenic distance and immunological landscape in different age groups and populations. Caution is required in the interpretation of pooled results across multiple seasons, since this can mask important variation in repeat vaccination effects between seasons. Multi-season clinical studies are needed to understand repeat vaccination effects and guide recommendations.

Realization of the axial next-nearest-neighbor Ising model in U 3 Al 2 Ge 3

DOE PAGES

Fobes, David M.; Lin, Shi-Zeng; Ghimire, Nirmal J.; ...

2017-11-09

Inmore » this paper, we report small-angle neutron scattering (SANS) measurements and theoretical modeling of U 3 Al 2 Ge 3 . Analysis of the SANS data reveals a phase transition to sinusoidally modulated magnetic order at T N = 63 K to be second order and a first-order phase transition to ferromagnetic order at T c = 48 K. Within the sinusoidally modulated magnetic phase (T c < T < T N), we uncover a dramatic change, by a factor of 3, in the ordering wave vector as a function of temperature. Finally, these observations all indicate that U 3 Al 2 Ge 3 is a close realization of the three-dimensional axial next-nearest-neighbor Ising model, a prototypical framework for describing commensurate to incommensurate phase transitions in frustrated magnets.« less

Realization of the axial next-nearest-neighbor Ising model in U 3 Al 2 Ge 3

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

Fobes, David M.; Lin, Shi-Zeng; Ghimire, Nirmal J.

Inmore » this paper, we report small-angle neutron scattering (SANS) measurements and theoretical modeling of U 3 Al 2 Ge 3 . Analysis of the SANS data reveals a phase transition to sinusoidally modulated magnetic order at T N = 63 K to be second order and a first-order phase transition to ferromagnetic order at T c = 48 K. Within the sinusoidally modulated magnetic phase (T c < T < T N), we uncover a dramatic change, by a factor of 3, in the ordering wave vector as a function of temperature. Finally, these observations all indicate that U 3 Al 2 Ge 3 is a close realization of the three-dimensional axial next-nearest-neighbor Ising model, a prototypical framework for describing commensurate to incommensurate phase transitions in frustrated magnets.« less

70. Photocopy of 4' 10 x 3'10 Propeller, U.S. Coast ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

70. Photocopy of 4' 10 x 3'10 Propeller, U.S. Coast Guard 133 Ft. Tender. Columbian Bronze Corporation, Freeport, Long Island, New York, Coast Guard Headquarters Drawing No. 540-WAGL-4400-4, dated July 1953. Original drawing property of the U.S. Coast Guard. - U.S. Coast Guard Cutter WHITE HEATH, USGS Integrated Support Command Boston, 427 Commercial Street, Boston, Suffolk County, MA

Enhancements to BISON U-Zr Metallic Fuel X447 Example Problem

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

Galloway, Jack D.; Matthews, Christopher; Unal, Cetin

As development of a metallic fuel modeling capability in BISON has progressed, the need for an example problem used as a comparison basis was observed. Collaborative work between researchers at Los Alamos National Laboratory (LANL) and Idaho National Laboratory (INL) then proceeded to determine a viable rod to use as the basis and create a BISON input deck utilizing as many metallic fuel models as feasible. The basis chosen was what would be considered a generic rod from subassembly X447, an assembly irradiated in EBR-II towards the end of its operating life, heavily based on reported data for fuel pinmore » DP11. Thus, the approach was adopted to use flow characteristics from subassembly X447 as a basis for the convective heat transfer solution, power history and axial power profiles that are representative of rod DP11 from subassembly X447. The rod simulated is a U-10Zr wt% (U-22.5Zr at%) composition. A 2D-RZ mesh would be used to capture axial thermal hydraulic effects, axial swelling and stress-strain calculations over the full length of the rod. After initial work was invested, a refinement of the various models and input parameters was conducted to ensure consistency between operator-declared conditions, model input requirements and those represented in the example problem. This report serves as a synopsis of the enhancements and refinements to the example problem conducted throughout the 2016 fiscal year.« less

Non-RVD mutations that enhance the dynamics of the TAL repeat array along the superhelical axis improve TALEN genome editing efficacy

PubMed Central

Tochio, Naoya; Umehara, Kohei; Uewaki, Jun-ichi; Flechsig, Holger; Kondo, Masaharu; Dewa, Takehisa; Sakuma, Tetsushi; Yamamoto, Takashi; Saitoh, Takashi; Togashi, Yuichi; Tate, Shin-ichi

2016-01-01

Transcription activator-like effector (TALE) nuclease (TALEN) is widely used as a tool in genome editing. The DNA binding part of TALEN consists of a tandem array of TAL-repeats that form a right-handed superhelix. Each TAL-repeat recognises a specific base by the repeat variable diresidue (RVD) at positions 12 and 13. TALEN comprising the TAL-repeats with periodic mutations to residues at positions 4 and 32 (non-RVD sites) in each repeat (VT-TALE) exhibits increased efficacy in genome editing compared with a counterpart without the mutations (CT-TALE). The molecular basis for the elevated efficacy is unknown. In this report, comparison of the physicochemical properties between CT- and VT-TALEs revealed that VT-TALE has a larger amplitude motion along the superhelical axis (superhelical motion) compared with CT-TALE. The greater superhelical motion in VT-TALE enabled more TAL-repeats to engage in the target sequence recognition compared with CT-TALE. The extended sequence recognition by the TAL-repeats improves site specificity with limiting the spatial distribution of FokI domains to facilitate their dimerization at the desired site. Molecular dynamics simulations revealed that the non-RVD mutations alter inter-repeat hydrogen bonding to amplify the superhelical motion of VT-TALE. The TALEN activity is associated with the inter-repeat hydrogen bonding among the TAL repeats. PMID:27883072

1,25-Dihydroxyvitamin D(3) Inhibits Podocyte uPAR Expression and Reduces Proteinuria

PubMed Central

Liu, Shuangxin; Xie, Shaoting; Yang, Yun; Ma, Juan; Deng, Yujun; Wang, Wenjian; Xu, Lixia; Li, Ruizhao; Zhang, Li; Yu, Chunping; Shi, Wei

2013-01-01

Background Accumulating studies have demonstrated that 1,25-Dihydroxyvitamin D(3) (1,25(OH)2D3) reduces proteinuria and protects podocytes from injury. Recently, urokinase receptor (uPAR) and its soluble form have been shown to cause podocyte injury and focal segmental glomerulosclerosis (FSGS). Here, our findings showed that 1,25(OH)2D3 did inhibit podocyte uPAR expression and attenuate proteinuria and podocyte injury. Methodology/Principal Findings In this study, the antiproteinuric effect of 1,25(OH)2D3 was examined in the lipopolysaccharide mice model of transient proteinuria (LPS mice) and in the 5/6 nephrectomy rat FSGS model(NTX rats). uPAR protein expression were tested by flow cytometry, immune cytochemistry and western blot analysis, and uPAR mRNA expression by real-time quantitative PCR in cultured podocytes and kidney glomeruli isolated from mice and rats. Podocyte motility was observed by transwell migration assay and wound healing assay. Podocyte foot processes effacement was identified by transmission electron microscopy. We found that 1,25(OH)2D3 inhibited podocyte uPAR mRNA and protein synthesis in LPS-treated podocytes, LPS mice and NTX rats, along with 1,25(OH)2D3 reducing proteinuria in NTX rats and LPS mice.1,25(OH)2D3 reduced glomerulosclerosis in NTX rats and alleviated podocyte foot processes effacement in LPS mice. Transwell migration assay and wound healing assay showed that LPS-induced podocyte motility, irrespective of random or directed motility, were substantially reduced by 1,25(OH)2D3. Conclusions/Significance Our results demonstrated that 1,25(OH)2D3 inhibited podocyte uPAR expression in vitro and in vivo, which may be an unanticipated off target effect of 1,25(OH)2D3 and explain its antiproteinuric effect in the 5/6 nephrectomy rat FSGS model and the LPS mouse model of transient proteinuria. PMID:23741418

Short- or long-rest intervals during repeated-sprint training in soccer?

PubMed

Iaia, F Marcello; Fiorenza, Matteo; Larghi, Luca; Alberti, Giampietro; Millet, Grégoire P; Girard, Olivier

2017-01-01

The present study compared the effects of two repeated-sprint training (RST) programs, differing in duration of the between-sprint rest intervals, on various soccer-related exercise performances. For 5 weeks during the competitive season, twenty-nine young trained male soccer players either replaced two of their habitual fitness conditioning sessions with RST characterized by short (5-15; n = 9) or long (5-30; n = 10) rest intervals, or served as control (n = 10). The 5-15 and 5-30 protocols consisted of 6 repetitions of 30-m (~5 s) straight-line sprints interspersed with 15 s or 30 s of passive recovery, respectively. 5-15 improved 200-m sprint time (2.0±1.5%; p<0.05) and had a likely positive impact on 20-m sprint performance, whereas 5-30 lowered the 20-m sprint time (2.7±1.6%; p<0.05) but was only possibly effective for enhancing the 200-m sprint performance. The distance covered during the Yo-Yo Intermittent Recovery Test Level 2 increased following 5-15 (11.4±5.0%; p<0.05), which was possibly better than the non-significant 6.5% enhancement observed in 5-30. Improvements in the total time of a repeated-sprint ability test were possibly greater following 5-30 (3.6±0.9%; p<0.05) compared to 5-15 (2.6±1.1%; p<0.05). Both RST interventions led to similar beneficial (p<0.05) reductions in the percentage decrement score (~30%) of the repeated-sprint ability test as well as in blood lactate concentration during submaximal exercise (17-18%). No changes occurred in the control group. In soccer players, RST over a 5-week in-season period is an efficient means to simultaneously develop different components of fitness relevant to match performance, with different benefits induced by shorter compared to longer rest intervals.

Short- or long-rest intervals during repeated-sprint training in soccer?

PubMed Central

Iaia, F. Marcello; Fiorenza, Matteo; Larghi, Luca; Alberti, Giampietro; Millet, Grégoire P.; Girard, Olivier

2017-01-01

The present study compared the effects of two repeated-sprint training (RST) programs, differing in duration of the between-sprint rest intervals, on various soccer-related exercise performances. For 5 weeks during the competitive season, twenty-nine young trained male soccer players either replaced two of their habitual fitness conditioning sessions with RST characterized by short (5–15; n = 9) or long (5–30; n = 10) rest intervals, or served as control (n = 10). The 5–15 and 5–30 protocols consisted of 6 repetitions of 30-m (~5 s) straight-line sprints interspersed with 15 s or 30 s of passive recovery, respectively. 5–15 improved 200-m sprint time (2.0±1.5%; p<0.05) and had a likely positive impact on 20-m sprint performance, whereas 5–30 lowered the 20-m sprint time (2.7±1.6%; p<0.05) but was only possibly effective for enhancing the 200-m sprint performance. The distance covered during the Yo-Yo Intermittent Recovery Test Level 2 increased following 5–15 (11.4±5.0%; p<0.05), which was possibly better than the non-significant 6.5% enhancement observed in 5–30. Improvements in the total time of a repeated-sprint ability test were possibly greater following 5–30 (3.6±0.9%; p<0.05) compared to 5–15 (2.6±1.1%; p<0.05). Both RST interventions led to similar beneficial (p<0.05) reductions in the percentage decrement score (~30%) of the repeated-sprint ability test as well as in blood lactate concentration during submaximal exercise (17–18%). No changes occurred in the control group. In soccer players, RST over a 5-week in-season period is an efficient means to simultaneously develop different components of fitness relevant to match performance, with different benefits induced by shorter compared to longer rest intervals. PMID:28199402

Effects of repeated Valsalva maneuver straining on cardiac and vasoconstrictive baroreflex responses

NASA Technical Reports Server (NTRS)

Convertino, Victor A.; Ratliff, Duane A.; Doerr, Donald F.; Ludwig, David A.; Muniz, Gary W.; Benedetti, Erik; Chavarria, Jose; Koreen, Susan; Nguyen, Claude; Wang, Jeff

2003-01-01

INTRODUCTION: We hypothesized that repeated respiratory straining maneuvers (repeated SM) designed to elevate arterial BPs (arterial baroreceptor loading) would acutely increase baroreflex responses. METHODS: We tested this hypothesis by measuring cardiac baroreflex responses to carotid baroreceptor stimulation (neck pressures), and changes in heart rate and diastolic BP after reductions in BP induced by a 15-s Valsalva maneuver in 10 female and 10 male subjects at 1, 3, 6, and 24 h after performing repeated SM. Baroreflex responses were also measured in each subject at 1, 3, 6, and 24 h at the same time on a separate day without repeated SM (control) in a randomized, counter-balanced cross-over experimental design. RESULTS: There was no statistical difference in carotid-cardiac and peripheral vascular baroreflex responses measured across time following repeated SM compared with the control condition. Integrated cardiac baroreflex response (deltaHR/ deltaSBP) measured during performance of a Valsalva maneuver was increased by approximately 50% to 1.1 +/- 0.2 bpm x mm Hg(-1) at 1 h and 1.0 +/- 0.1 bpm x mm Hg(-1) at 3 h following repeated SM compared with the control condition (0.7 +/- 0.1 bpm x mm Hg(-1) at both 1 and 3 h, respectively). However, integrated cardiac baroreflex response after repeated SM returned to control levels at 6 and 24 h after training. These responses did not differ between men and women. CONCLUSIONS: Our results are consistent with the notion that arterial baroreceptor loading induced by repeated SM increased aortic, but not carotid, cardiac baroreflex responses for as long as 3 h after repeated SM. We conclude that repeated SM increases cardiac baroreflex responsiveness which may provide patients, astronauts, and high-performance aircraft pilots with protection from development of orthostatic hypotension.

Self-interaction corrected LDA + U investigations of BiFeO3 properties: plane-wave pseudopotential method

NASA Astrophysics Data System (ADS)

Yaakob, M. K.; Taib, M. F. M.; Lu, L.; Hassan, O. H.; Yahya, M. Z. A.

2015-11-01

The structural, electronic, elastic, and optical properties of BiFeO3 were investigated using the first-principles calculation based on the local density approximation plus U (LDA + U) method in the frame of plane-wave pseudopotential density functional theory. The application of self-interaction corrected LDA + U method improved the accuracy of the calculated properties. Results of structural, electronic, elastic, and optical properties of BiFeO3, calculated using the LDA + U method were in good agreement with other calculation and experimental data; the optimized choice of on-site Coulomb repulsion U was 3 eV for the treatment of strong electronic localized Fe 3d electrons. Based on the calculated band structure and density of states, the on-site Coulomb repulsion U had a significant effect on the hybridized O 2p and Fe 3d states at the valence and the conduction band. Moreover, the elastic stiffness tensor, the longitudinal and shear wave velocities, bulk modulus, Poisson’s ratio, and the Debye temperature were calculated for U = 0, 3, and 6 eV. The elastic stiffness tensor, bulk modulus, sound velocities, and Debye temperature of BiFeO3 consistently decreased with the increase of the U value.

Roles for herpes simplex virus type 1 U{sub L}34 and U{sub S}3 proteins in disrupting the nuclear lamina during herpes simplex virus type 1 egress

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

Bjerke, Susan L.; Roller, Richard J.

2006-04-10

Cells infected with wild type HSV-1 showed significant lamin A/C and lamin B rearrangement, while U{sub L}34-null virus-infected cells exhibited few changes in lamin localization, indicating that U{sub L}34 is necessary for lamin disruption. During HSV infection, U{sub S}3 limited the development of disruptions in the lamina, since cells infected with a U{sub S}3-null virus developed large perforations in the lamin layer. U{sub S}3 regulation of lamin disruption does not correlate with the induction of apoptosis. Expression of either U{sub L}34 or U{sub S}3 proteins alone disrupted lamin A/C and lamin B localization. Expression of U{sub L}34 and U{sub S}3more » together had little effect on lamin A/C localization, suggesting a regulatory interaction between the two proteins. The data presented in this paper argue for crucial roles for both U{sub L}34 and U{sub S}3 in regulating the state of the nuclear lamina during viral infection.« less

β3-Adrenergic receptors, adipokines and neuroendocrine activation during stress induced by repeated immune challenge in male and female rats.

PubMed

Csanova, Agnesa; Hlavacova, Natasa; Hasiec, Malgorzata; Pokusa, Michal; Prokopova, Barbora; Jezova, Daniela

2017-05-01

The main hypothesis of the study is that stress associated with repeated immune challenge has an impact on β 3 -adrenergic receptor gene expression in the brain. Sprague-Dawley rats were intraperitoneally injected with increasing doses of lipopolysaccharide (LPS) for five consecutive days. LPS treatment was associated with body weight loss and increased anxiety-like behavior. In LPS-treated animals of both sexes, β 3 -receptor gene expression was increased in the prefrontal cortex but not the hippocampus. LPS treatment decreased β 3 -receptor gene expression in white adipose tissue with higher values in males compared to females. In the adipose tissue, LPS reduced peroxisome proliferator-activated receptor-gamma, leptin and adiponectin gene expression, but increased interleukin-6 expression, irrespective of sex. Repeated immune challenge resulted in increased concentrations of plasma aldosterone and corticosterone with higher values of corticosterone in females compared to males. Concentrations of dehydroepiandrosterone (DHEA) in plasma were unaffected by LPS, while DHEA levels in the frontal cortex were lower in the LPS-treated animals compared to the controls. Thus, changes of DHEA levels in the brain take place irrespective of the changes of this neurosteroid in plasma. We have provided the first evidence on stress-induced increase in β 3 -adrenergic receptor gene expression in the brain. Greater reduction of β 3 -adrenergic receptor expression in the adipose tissue and of the body weight gain by repeated immune challenge in male than in female rats suggests sex differences in the role of β 3 -adrenergic receptors in the metabolic functions. LPS-induced changes in adipose tissue regulatory factors and hormone concentrations might be important for coping with chronic infections.

Reduction of Heavy Metals by Cytochrome c(3)

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

ABDELOUAS,A.; GONG,W.L.; LUTZE,W.

2000-01-18

We report on reduction and precipitation of Se(VI), Pb(II), CU(II), U(VI), Mo(VI), and Cr(VI) in water by cytochrome c{sub 3} isolated from Desulfomicrobium baczdatum [strain 9974]. The tetraheme protein cytochrome c{sub 3} was reduced by sodium dithionite. Redox reactions were monitored by UV-visible spectroscopy of cytochrome c{sub 3}. Analytical electron microscopy work showed that Se(VI), Pb(II), and CU(II) were reduced to the metallic state, U(W) and Mo(W) to U(IV) and Mo(IV), respectively, and Cr(VI) probably to Cr(III). U(IV) and Mo(W) precipitated as oxides and Cr(III) as an amorphous hydroxide. Cytochrome c{sub 3} was used repeatedly in the same solution withoutmore » loosing its effectiveness. The results suggest usage of cytochrome c{sub 3} to develop innovative and environmentally benign methods to remove heavy metals from waste- and groundwater.« less

Value of repeat CT scans in low back pain and radiculopathy.

PubMed

Schroeder, Josh E; Barzilay, Yair; Kaplan, Leon; Itshayek, Eyal; Hiller, Nurith

2016-02-01

We assessed the clinical value of repeat spine CT scan in 108 patients aged 18-60 years who underwent repeat lumbar spine CT scan for low back pain or radiculopathy from January 2008 to December 2010. Patients with a neoplasm or symptoms suggesting underlying disease were excluded from the study. Clinical data was retrospectively reviewed. Index examinations and repeat CT scan performed at a mean of 24.3 ± 11.3 months later were compared by a senior musculoskeletal radiologist. Disc abnormalities (herniation, sequestration, bulge), spinal stenosis, disc space narrowing, and bony changes (osteophytes, fractures, other changes) were documented. Indications for CT scan were low back pain (60 patients, 55%), radiculopathy (46 patients, 43%), or nonspecific back pain (two patients, 2%). A total of 292 spine pathologies were identified in 98 patients (90.7%); in 10 patients (9.3%) no spine pathology was seen on index or repeat CT scan. At repeat CT scan, 269/292 pathologies were unchanged (92.1%); 10/292 improved (3.4%), 8/292 worsened (2.8%, disc herniation or spinal stenosis), and five new pathologies were identified. No substantial therapeutic change was required in patients with worsened or new pathology. Added diagnostic value from repeat CT scan performed within 2-3 years was rare in patients suffering chronic or recurrent low back pain or radiculopathy, suggesting that repeat CT scan should be considered only in patients with progressive neurologic deficits, new neurologic complaints, or signs implying serious underlying conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Geometric Positioning for Satellite Imagery without Ground Control Points by Exploiting Repeated Observation.

PubMed

Ma, Zhenling; Wu, Xiaoliang; Yan, Li; Xu, Zhenliang

2017-01-26

With the development of space technology and the performance of remote sensors, high-resolution satellites are continuously launched by countries around the world. Due to high efficiency, large coverage and not being limited by the spatial regulation, satellite imagery becomes one of the important means to acquire geospatial information. This paper explores geometric processing using satellite imagery without ground control points (GCPs). The outcome of spatial triangulation is introduced for geo-positioning as repeated observation. Results from combining block adjustment with non-oriented new images indicate the feasibility of geometric positioning with the repeated observation. GCPs are a must when high accuracy is demanded in conventional block adjustment; the accuracy of direct georeferencing with repeated observation without GCPs is superior to conventional forward intersection and even approximate to conventional block adjustment with GCPs. The conclusion is drawn that taking the existing oriented imagery as repeated observation enhances the effective utilization of previous spatial triangulation achievement, which makes the breakthrough for repeated observation to improve accuracy by increasing the base-height ratio and redundant observation. Georeferencing tests using data from multiple sensors and platforms with the repeated observation will be carried out in the follow-up research.

Comparing Simulated and Theoretical Sampling Distributions of the U3 Person-Fit Statistic.

ERIC Educational Resources Information Center

Emons, Wilco H. M.; Meijer, Rob R.; Sijtsma, Klaas

2002-01-01

Studied whether the theoretical sampling distribution of the U3 person-fit statistic is in agreement with the simulated sampling distribution under different item response theory models and varying item and test characteristics. Simulation results suggest that the use of standard normal deviates for the standardized version of the U3 statistic may…

Infrared radiative decay dynamics from the γ 1u (3P2), H 1u (3P1), and 1u (1D2) ion-pair states of I2 observed by a perturbation facilitated optical-optical double resonance technique

NASA Astrophysics Data System (ADS)

Hoshino, Shoma; Araki, Mitsunori; Nakano, Yukio; Ishiwata, Takashi; Tsukiyama, Koichi

2016-01-01

We report the spectroscopic and temporal analyses on the amplified spontaneous emission (ASE) from the single rovibrational levels of the Ω = 1u ion-pair series, γ 1u (3P2), H 1u (3P1), and 1u (1D2), of I2 by using a perturbation facilitated optical-optical double resonance technique through the c 1 Π g ˜ B 3 Π ( 0u + ) hyperfine mixed valence state as the intermediate state. The ASE detected in the infrared region was assigned to the parallel transitions from the Ω = 1u ion-pair states down to the nearby Ω = 1g ion-pair states. The subsequent ultraviolet (UV) fluorescence from the Ω = 1g states was also observed and the relative vibrational populations in the Ω = 1g states were derived through the Franck-Condon simulation of the intensity pattern of the vibrational progression. In the temporal profiles of the UV fluorescence, an obvious delay in the onset of the fluorescence was recognized after the excitation laser pulse. These results revealed that ASE is a dominant energy relaxation process between the Ω = 1u and 1g ion-pair states of I2. Finally, the lifetimes of the relevant ion-pair states were evaluated by temporal analyses of the UV fluorescence. The propensity was found which was the longer lifetime in the upper level of the ASE transitions tends to give intense ASE.

Challenging, Eye-Opening, and Changing U.S. Teacher Training in Korea: Creating Experiences That Will Enhance Global Perspectives

ERIC Educational Resources Information Center

Oh, Kevin; Nussli, Natalie

2014-01-01

This case study explored the short-term international experience of pre-service teachers to create and enhance global perspectives. These teachers (n = 5), all female graduate students at a university in the U.S., were fully immersed in a foreign culture for three weeks while teaching English to primary and secondary students in Korea. Pre-,…

Enhanced axion-photon coupling in GUT with hidden photon

NASA Astrophysics Data System (ADS)

Daido, Ryuji; Takahashi, Fuminobu; Yokozaki, Norimi

2018-05-01

We show that the axion coupling to photons can be enhanced in simple models with a single Peccei-Quinn field, if the gauge coupling unification is realized by a large kinetic mixing χ = O (0.1) between hypercharge and unbroken hidden U(1)H. The key observation is that the U(1)H gauge coupling should be rather strong to induce such large kinetic mixing, leading to enhanced contributions of hidden matter fields to the electromagnetic anomaly. We find that the axion-photon coupling is enhanced by about a factor of 10-100 with respect to the GUT-axion models with E / N = 8 / 3.

Motor Imagery Practice for Enhancing Elevé Performance Among Professional Dancers: A Pilot Study.

PubMed

Abraham, Amit; Dunsky, Ayelet; Dickstein, Ruth

2016-09-01

Elevé is a core dance movement requiring the greatest ankle plantarflexion (PF) range of motion (ROM). One possible way to enhance elevé performance is by using motor imagery practice (MIP). The aims of this pilot study were to investigate: 1) functional ankle PF maximal angles and ROM while performing elevé among professional dancers, 2) the effect of MIP on enhancing elevé performance, and 3) participants' views on the MIP intervention and its feasibility in a professional dance company setting. Five professional dancers, mean age 31 yrs (SD 1.87), participated in a 2-week MIP intervention. Data on ankle PF maximal angles and ROM were collected pre- and post-intervention using 3-dimensional motion capture while performing repeat (10 repetitions) and static (10 sec) elevé. At baseline, ankle PF maximal angles were 169.20° (SD 2.81°) and 168.36° (2.23°) and ankle PF ROM were 40.21° (3.35°) and 35.94° (3.95°) for the repeat and static tasks, respectively. After the MIP intervention, ankle PF maximal angles were 170.28° (4.26°) and 170.74° (3.77°) and ankle PF ROM were 41.53° (2.33°) and 39.30° (2.30°) for the repeat and static tasks, respectively. Feasibility of MIP was established with 100% compliance and positive views were expressed by participants. The results suggest MIP holds potential as an adjunct training method for enhancing elevé performance among professional dancers.

Pulsed coherent population trapping with repeated queries for producing single-peaked high contrast Ramsey interference

NASA Astrophysics Data System (ADS)

Warren, Z.; Shahriar, M. S.; Tripathi, R.; Pati, G. S.

2018-02-01

A repeated query technique has been demonstrated as a new interrogation method in pulsed coherent population trapping for producing single-peaked Ramsey interference with high contrast. This technique enhances the contrast of the central Ramsey fringe by nearly 1.5 times and significantly suppresses the side fringes by using more query pulses ( >10) in the pulse cycle. Theoretical models have been developed to simulate Ramsey interference and analyze the characteristics of the Ramsey spectrum produced by the repeated query technique. Experiments have also been carried out employing a repeated query technique in a prototype rubidium clock to study its frequency stability performance.

On the Search for Nuclear Resonance Fluorescence Signatures of 235U and 238U above 3 MeV

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

Warren, Glen A.; Caggiano, Joseph A.; Bertozzi, William

Nuclear resonance fluorescence is a physical process that provides an isotope-specific signature that could be used for the identification and characterization of materials. The technique involves the detection of prompt discrete-energy photons emitted from a sample that is exposed to MeV-energy photons. Potential applications of the technique range from detection of high explosives to characterization of special nuclear materials such as 235U. Pacific Northwest National Laboratory and Passport Systems have collaborated to conduct a pair of measurements to search for a nuclear resonance fluorescence response of 235U above 3 MeV and of 238U above 5 MeV using an 8 gmore » sample of highly enriched uranium and a 90 g sample of depleted uranium. No new signatures were observed. The minimum detectable integrated cross section for 235U is presented.« less

Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 4 h apart Human pharmacology of MDMA after repeated doses taken 4 h apart.

PubMed

Farré, Magí; Tomillero, Angels; Pérez-Mañá, Clara; Yubero, Samanta; Papaseit, Esther; Roset, Pere-Nolasc; Pujadas, Mitona; Torrens, Marta; Camí, Jordi; de la Torre, Rafael

2015-10-01

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.