γ-H2AX Kinetic Profile in Mouse Lymphocytes Exposed to the Internal Emitters Cesium-137 and Strontium-90

PubMed Central

Turner, Helen C.; Shuryak, Igor; Weber, Waylon; Doyle-Eisele, Melanie; Melo, Dunstana; Guilmette, Raymond; Amundson, Sally A.; Brenner, David J.

2015-01-01

In the event of a dirty bomb scenario or an industrial nuclear accident, a significant dose of volatile radionuclides such as 137Cs and 90Sr may be dispersed into the atmosphere as a component of fallout and inhaled or ingested by hundreds and thousands of people. To study the effects of prolonged exposure to ingested radionuclides, we have performed long-term (30 day) internal-emitter mouse irradiations using soluble-injected 137CsCl and 90SrCl2 radioisotopes. The effect of ionizing radiation on the induction and repair of DNA double strand breaks (DSBs) in peripheral mouse lymphocytes in vivo was determined using the γ-H2AX biodosimetry marker. Using a serial sacrifice experimental design, whole-body radiation absorbed doses for 137Cs (0 to 10 Gy) and 90Sr (0 to 49 Gy) were delivered over 30 days following exposure to each radionuclide. The committed absorbed doses of the two internal emitters as a function of time post exposure were calculated based on their retention parameters and their derived dose coefficients for each specific sacrifice time. In order to measure the kinetic profile for γ-H2AX, peripheral blood samples were drawn at 5 specific timed dose points over the 30-day study period and the total γ-H2AX nuclear fluorescence per lymphocyte was determined using image analysis software. A key finding was that a significant γ-H2AX signal was observed in vivo several weeks after a single radionuclide exposure. A mechanistically-motivated model was used to analyze the temporal kinetics of γ-H2AX fluorescence. Exposure to either radionuclide showed two peaks of γ-H2AX: one within the first week, which may represent the death of mature, differentiated lymphocytes, and the second at approximately three weeks, which may represent the production of new lymphocytes from damaged progenitor cells. The complexity of the observed responses to internal irradiation is likely caused by the interplay between continual production and repair of DNA damage, cell cycle effects and apoptosis. PMID:26618801

γ-H2AX Kinetic Profile in Mouse Lymphocytes Exposed to the Internal Emitters Cesium-137 and Strontium-90.

PubMed

Turner, Helen C; Shuryak, Igor; Weber, Waylon; Doyle-Eisele, Melanie; Melo, Dunstana; Guilmette, Raymond; Amundson, Sally A; Brenner, David J

2015-01-01

In the event of a dirty bomb scenario or an industrial nuclear accident, a significant dose of volatile radionuclides such as 137Cs and 90Sr may be dispersed into the atmosphere as a component of fallout and inhaled or ingested by hundreds and thousands of people. To study the effects of prolonged exposure to ingested radionuclides, we have performed long-term (30 day) internal-emitter mouse irradiations using soluble-injected 137CsCl and 90SrCl2 radioisotopes. The effect of ionizing radiation on the induction and repair of DNA double strand breaks (DSBs) in peripheral mouse lymphocytes in vivo was determined using the γ-H2AX biodosimetry marker. Using a serial sacrifice experimental design, whole-body radiation absorbed doses for 137Cs (0 to 10 Gy) and 90Sr (0 to 49 Gy) were delivered over 30 days following exposure to each radionuclide. The committed absorbed doses of the two internal emitters as a function of time post exposure were calculated based on their retention parameters and their derived dose coefficients for each specific sacrifice time. In order to measure the kinetic profile for γ-H2AX, peripheral blood samples were drawn at 5 specific timed dose points over the 30-day study period and the total γ-H2AX nuclear fluorescence per lymphocyte was determined using image analysis software. A key finding was that a significant γ-H2AX signal was observed in vivo several weeks after a single radionuclide exposure. A mechanistically-motivated model was used to analyze the temporal kinetics of γ-H2AX fluorescence. Exposure to either radionuclide showed two peaks of γ-H2AX: one within the first week, which may represent the death of mature, differentiated lymphocytes, and the second at approximately three weeks, which may represent the production of new lymphocytes from damaged progenitor cells. The complexity of the observed responses to internal irradiation is likely caused by the interplay between continual production and repair of DNA damage, cell cycle effects and apoptosis.

Event structure and cognitive control.

PubMed

Reimer, Jason F; Radvansky, Gabriel A; Lorsbach, Thomas C; Armendarez, Joseph J

2015-09-01

Recently, a great deal of research has demonstrated that although everyday experience is continuous in nature, it is parsed into separate events. The aim of the present study was to examine whether event structure can influence the effectiveness of cognitive control. Across 5 experiments we varied the structure of events within the AX-CPT by shifting the spatial location of cues and probes on a computer screen. When location shifts were present, a pattern of AX-CPT performance consistent with enhanced cognitive control was found. To test whether the location shift effects were caused by the presence of event boundaries per se, other aspects of the AX-CPT were manipulated, such as the color of cues and probes and the inclusion of a distractor task during the cue-probe delay. Changes in cognitive control were not found under these conditions, suggesting that the location shift effects were specifically related to the formation of separate event models. Together, these results can be accounted for by the Event Horizon Model and a representation-based theory of cognitive control, and suggest that cognitive control can be influenced by the surrounding environmental structure. (c) 2015 APA, all rights reserved).

Interactions of task and subject variables among continuous performance tests.

PubMed

Denney, Colin B; Rapport, Mark D; Chung, Kyong-Mee

2005-04-01

Contemporary models of working memory suggest that target paradigm (TP) and target density (TD) should interact as influences on error rates derived from continuous performance tests (CPTs). The present study evaluated this hypothesis empirically in a typically developing, ethnically diverse sample of children. The extent to which scores based on different combinations of these task parameters showed different patterns of relationship to age, intelligence, and gender was also assessed. Four continuous performance tests were derived by combining two target paradigms (AX and repeated letter target stimuli) with two levels of target density (8.3% and 33%). Variations in mean omission (OE) and commission (CE) error rates were examined within and across combinations of TP and TD. In addition, a nested series of structural equation models was utilized to examine patterns of relationship among error rates, age, intelligence, and gender. Target paradigm and target density interacted as influences on error rates. Increasing density resulted in higher OE and CE rates for the AX paradigm. In contrast, the high density condition yielded a decline in OE rates accompanied by a small increase in CEs using the repeated letter CPT. Target paradigms were also distinguishable on the basis of age when using OEs as the performance measure, whereas combinations of age and intelligence distinguished between density levels but not target paradigms using CEs as the dependent measure. Different combinations of target paradigm and target density appear to yield scores that are conceptually and psychometrically distinguishable. Consequently, developmentally appropriate interpretation of error rates across tasks may require (a) careful analysis of working memory and attentional resources required for successful performance, and (b) normative data bases that are differently stratified with respect to combinations of age and intelligence.

γH2AX foci on apparently intact mitotic chromosomes: Not signatures of misrejoining events but signals of unresolved DNA damage

PubMed Central

Martín, Marta; Terradas, Mariona; Hernández, Laia; Genescà, Anna

2014-01-01

The presence of γH2AX foci on apparently intact mitotic chromosomes is controversial because they challenge the assumed relationship between γH2AX foci and DNA double-strand breaks (DSBs). In this work, we show that after irradiation during interphase, a variety of γH2AX foci are scored in mitotic cells. Surprisingly, approximately 80% of the γH2AX foci spread over apparently undamaged chromatin at Terminal or Interstitial positions and they can display variable sizes, thus being classified as Small, Medium and Big foci. Chromosome and chromatid breaks that reach mitosis are spotted with Big (60%) and Medium (30%) Terminal γH2AX foci, but very rarely are they signaled with Small γH2AX foci. To evaluate if Interstitial γH2AX foci might be signatures of misrejoining, an mFISH analysis was performed on the same slides. The results show that Interstitial γH2AX foci lying on apparently intact chromatin do not mark sites of misrejoining, and that misrejoined events were never signaled by a γH2AX foci during mitosis. Finally, when analyzing the presence of other DNA-damage response (DDR) factors we found that all γH2AX foci—regardless their coincidence with a visible break—always colocalized with MRE11, but not with 53BP1. This pattern suggests that these γH2AX foci may be hallmarks of both microscopically visible and invisible DNA damage, in which an active, although incomplete or halted DDR is taking place. PMID:25486563

γH2Ax Expression as a Potential Biomarker Differentiating between Low and High Grade Cervical Squamous Intraepithelial Lesions (SIL) and High Risk HPV Related SIL

PubMed Central

Kefala, Maria; Kottaridi, Christine; Spathis, Aris; Gouloumi, Alina-Roxani; Pouliakis, Abraham; Pappas, Asimakis; Sioulas, Vasileios; Chrelias, Charalambos; Karakitsos, Petros; Panayiotides, Ioannis

2017-01-01

Background γH2AX is a protein biomarker for double-stranded DNA breakage; its expression was studied in cervical squamous intraepithelial lesions and carcinomas. Methods Immunostaining for phospho-γH2AX was performed in sections from histologically confirmed cervical SIL and carcinomas, as well as from normal cervices used as controls. In total, 275 cases were included in the study: 112 low grade SIL (LGSIL), 99 high grade SIL (HGSIL), 24 squamous cell carcinoma (SCC), 12 adenocarcinoma and 28 cervical specimens with no essential lesions. Correlation of histological grading, high risk vs. low risk HPV virus presence, activated vs. non-activated status (by high risk HPV mRNA expression) and γH2AX expression in both basal and surface segments of the squamous epithelium was performed. Results Gradual increase of both basal and surface γH2AX expression was noted up from normal cervices to LGSIL harboring a low risk HPV type, to LGSIL harboring a high risk virus at a non-activated state (p<0.05). Thereafter, both basal and surface γH2AX expression dropped in LGSIL harboring a high risk virus at an activated state and in HGSIL. Conclusions γH2AX could serve as a potential biomarker discriminating between LGSIL and HGSIL, as well as between LGSIL harboring high risk HPV at an activated state. PMID:28118377

Effects of caffeine ingestion on endurance performance in mentally fatigued individuals.

PubMed

Azevedo, Rafael; Silva-Cavalcante, Marcos David; Gualano, Bruno; Lima-Silva, Adriano E; Bertuzzi, Romulo

2016-12-01

To examine the effects of caffeine ingestion on physiological and perceptual responses in mentally fatigued individuals. Eight male physically active subjects completed four cycling constant-workload tests in four experimental conditions at 80 % of maximal power output: control (C), mental fatigue (MF), mental fatigue plus caffeine ingestion (5 mg/kg) (MF-CAF), and mental fatigue plus placebo (MF-PLA). The mental fatigue was induced by a continuous performance task A-X version (AX-CPT). Before and after the AX-CPT, the profile of mood state (POMS) and blood samples for lactate measurement were collected. Oxygen consumption ([Formula: see text]), rating of perceived exertion (RPE), and electromyography (EMG) activity were measured during the cycling test. The time to exhaustion in C, MF, MF-PLA, and MF-CAF were 251 ± 30, 222 ± 23, 248 ± 28, and 285 ± 42 s, respectively. Delta values (corrected by C condition) were higher in MF-CAF than MF (P = 0.031). MF-CAF reported higher Vigor scores when compared with C (P = 0.046) and MF (P = 0.020). RPE at the first minute was significantly higher in MF-PLA than in C (P = 0.050); at the second minute, RPE was higher in MF-PLA than in C (P = 0.049) and MF-CAF (P = 0.048). EMG activity was not different between the conditions. Caffeine ingestion increased approximately 14 % endurance performance after the induction of mental fatigue. This effect was accompanied by a tendency to improvement in mood state (i.e., vigor). Therefore, caffeine ingestion can promote a beneficial effect on endurance performance in mentally fatigued individuals.

Neural circuitry of emotional and cognitive conflict revealed through facial expressions.

PubMed

Chiew, Kimberly S; Braver, Todd S

2011-03-09

Neural systems underlying conflict processing have been well studied in the cognitive realm, but the extent to which these overlap with those underlying emotional conflict processing remains unclear. A novel adaptation of the AX Continuous Performance Task (AX-CPT), a stimulus-response incompatibility paradigm, was examined that permits close comparison of emotional and cognitive conflict conditions, through the use of affectively-valenced facial expressions as the response modality. Brain activity was monitored with functional magnetic resonance imaging (fMRI) during performance of the emotional AX-CPT. Emotional conflict was manipulated on a trial-by-trial basis, by requiring contextually pre-cued facial expressions to emotional probe stimuli (IAPS images) that were either affectively compatible (low-conflict) or incompatible (high-conflict). The emotion condition was contrasted against a matched cognitive condition that was identical in all respects, except that probe stimuli were emotionally neutral. Components of the brain cognitive control network, including dorsal anterior cingulate cortex (ACC) and lateral prefrontal cortex (PFC), showed conflict-related activation increases in both conditions, but with higher activity during emotion conditions. In contrast, emotion conflict effects were not found in regions associated with affective processing, such as rostral ACC. These activation patterns provide evidence for a domain-general neural system that is active for both emotional and cognitive conflict processing. In line with previous behavioural evidence, greatest activity in these brain regions occurred when both emotional and cognitive influences additively combined to produce increased interference.

Neural Circuitry of Emotional and Cognitive Conflict Revealed through Facial Expressions

PubMed Central

Chiew, Kimberly S.; Braver, Todd S.

2011-01-01

Background Neural systems underlying conflict processing have been well studied in the cognitive realm, but the extent to which these overlap with those underlying emotional conflict processing remains unclear. A novel adaptation of the AX Continuous Performance Task (AX-CPT), a stimulus-response incompatibility paradigm, was examined that permits close comparison of emotional and cognitive conflict conditions, through the use of affectively-valenced facial expressions as the response modality. Methodology/Principal Findings Brain activity was monitored with functional magnetic resonance imaging (fMRI) during performance of the emotional AX-CPT. Emotional conflict was manipulated on a trial-by-trial basis, by requiring contextually pre-cued facial expressions to emotional probe stimuli (IAPS images) that were either affectively compatible (low-conflict) or incompatible (high-conflict). The emotion condition was contrasted against a matched cognitive condition that was identical in all respects, except that probe stimuli were emotionally neutral. Components of the brain cognitive control network, including dorsal anterior cingulate cortex (ACC) and lateral prefrontal cortex (PFC), showed conflict-related activation increases in both conditions, but with higher activity during emotion conditions. In contrast, emotion conflict effects were not found in regions associated with affective processing, such as rostral ACC. Conclusions/Significance These activation patterns provide evidence for a domain-general neural system that is active for both emotional and cognitive conflict processing. In line with previous behavioural evidence, greatest activity in these brain regions occurred when both emotional and cognitive influences additively combined to produce increased interference. PMID:21408006

Cast Study: National Naval Medical Center, A Graduate Management Project

DTIC Science & Technology

2002-06-10

USNR 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. pPDV^-- -’" !nDf-AxTT7ATION NATIONAL NAVAL MEDICAL CENTER BETHESDA 8901 WISCONSIN AVE...reinvented itself on July 3, 2000 when it transformed from a traditional stovepipe organization into a service line health care delivery system. In less...many diverse projects throughout the organization . Commander Steve Griffitts, USN... for your continual cooperation and flexibility as I pursued my

The burden of non-radiographic axial spondyloarthritis.

PubMed

Boonen, Annelies; Sieper, Joachim; van der Heijde, Désirée; Dougados, Maxime; Bukowski, Jack F; Valluri, Satish; Vlahos, Bonnie; Kotak, Sameer

2015-04-01

To identify patients earlier, new classification criteria have been introduced for axial spondyloarthritis (axSpA). Patients who satisfy the clinical or imaging criteria for axSpA in the absence of definite sacroiliac joint changes on pelvic x-rays are classified as having non-radiographic axSpA. Although the burden associated with radiographic axSpA (i.e., ankylosing spondylitis) has been extensively studied, the impact of non-radiographic disease is not well understood. The purpose of this review is to provide an overview of the burden of illness in non-radiographic axSpA, including epidemiology and effects on patients׳ functioning and health-related quality of life (HR-QoL). A PubMed search was performed using relevant key words (e.g., "spondyloarthritis," "ankylosing spondylitis," "epidemiology," and "quality of life") to examine literature published from 2003 to 2013. Studies conducted to date suggest that radiographic progression is detected in approximately 10% of patients with non-radiographic axSpA over 2 years. Differences between patients with non-radiographic and radiographic axSpA were found in age, symptom duration, and gender distribution. Although less inflammation (i.e., lower C-reactive protein levels and less spinal inflammation on MRI) and less impairment in spinal mobility are observed in non-radiographic than in radiographic axSpA, the 2 conditions pose a similar burden in terms of disease activity, physical function, HR-QoL impairment. Patients with non-radiographic axSpA are more frequently female. Although patients with non-radiographic axSpA have shorter disease duration and lack radiological changes, they demonstrate a substantial burden of illness, with self-reported disease activity and functional impairments comparable to those found in patients with radiographic disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Trabecular bone score as an assessment tool to identify the risk of osteoporosis in axial spondyloarthritis: a case-control study.

PubMed

Kang, Kwi Young; Goo, Hye Yeon; Park, Sung-Hwan; Hong, Yeon Sik

2018-03-01

To compare the trabecular bone score (TBS) between patients with axial spondyloarthritis (axSpA) and matched normal controls and identify risk factors associated with a low TBS. TBS and BMD were assessed in the two groups (axSpA and control) using DXA. Osteoporosis risk factors and inflammatory markers were also assessed. Disease activity and radiographic progression in the sacroiliac joint and spine were evaluated in the axSpA group. Multivariate linear regression analysis was performed to identify risk factors associated with TBS. In the axSpA group, 248 subjects were enrolled; an equal number of age- and sex-matched subjects comprised the control group. The mean TBS was 1.43 (0.08) and 1.38 (0.12) in the control and axSpA groups, respectively (P < 0.001); BMD at the lumbar spine did not differ between the two groups. The TBS was negatively correlated with ESR and CRP levels in the axSpA group only (P < 0.001 and P = 0.007, respectively). Syndesmophytes in the axSpA group was associated with lower TBS (P < 0.001) but higher lumbar BMD (P = 0.021) vs controls. In the multivariate analyses, ESR, CRP and spinal radiographic progression were significantly associated with TBS. TBS assessments revealed poor bone quality in patients with axSpA compared with the matched controls. In axSpA, systemic inflammatory markers were negatively correlated with TBS and spinal radiographic progression and inflammatory markers were independently correlated with low TBS. TBS may, therefore, be a useful clinical tool to identify the risk of osteoporosis in patients with axSpA.

Performance testing of Zymomonas mobilis metabolically engineered for cofermentation of glucose, xylose, and arabinose.

PubMed

Lawford, Hugh G; Rousseau, Joyce D

2002-01-01

IOGEN Corporation of Ottawa, Canada, has recently built a 40t/d biomass-to-ethanol demonstration plant adjacent to its enzyme production facility. It has partnered with the University of Toronto to test the C6/C5 cofermenta-tion performance characteristics of the National Renewable Energy Labora-tory's metabolically engineered Zymomonas mobilis using various biomass hydrolysates. IOGEN's feedstocks are primarily agricultural wastes such as corn stover and wheat straw. Integrated recombinant Z. mobilis strain AX101 grows on D-xylose and/or L-arabinose as the sole carbon/energy sources and ferments these pentose sugars to ethanol in high yield. Strain AX101 lacks the tetracycline resistance gene that was a common feature of other recombinant Zm constructs. Genomic integration provides reliable cofermentation performance in the absence of antibiotics, another characteristic making strain AX101 attractive for industrial cellulosic ethanol production. In this work, IOGEN's biomass hydrolysate was simulated by a pure sugar medium containing 6% (w/v) glucose, 3% xylose, and 0.35% arabinose. At a level of 3 g/L (dry solids), corn steep liquor with inorganic nitrogen (0.8 g/L of ammonium chloride or 1.2 g/L of diammonium phosphate) was a cost-effective nutritional supplement. In the absence of acetic acid, the maximum volumetric ethanol productivity of a continuous fermentation at pH 5.0 was 3.54 g/L x h. During prolonged continuous fermentation, the efficiency of sugar-to-ethanol conversion (based on total sugar load) was maintained at >85%. At a level of 0.25% (w/v) acetic acid, the productivity decreased to 1.17 g/L x h at pH 5.5. Unlike integrated, xylose-utilizing rec Zm strain C25, strain AX101 produces less lactic acid as byproduct, owing to the fact that the Escherichia coli arabinose genes are inserted into a region of the host chromosome tentatively assigned to the gene for D-lactic acid dehydrogenase. In pH-controlled batch fermentations with sugar mixtures, the order of sugar exhaustion from the medium was glucose followed by xylose and arabinose. Both the total sugar load and the sugar ratio were shown to be important determinants for efficient cofermentation. Ethanol at a level of 3% (w/v) was implicated as both inhibitory to pentose fermentation and as a potentiator of acetic acid inhibition of pentose fermentation at pH 5.5. The effect of ethanol may have been underestimated in other assessments of acetic acid sensitivity. This work underscores the importance of employing similar assay conditions in making comparative assessments of biocatalyst fermentation performance.

Adapting the γ-H2AX assay for automated processing in human lymphocytes. 1. Technological aspects.

PubMed

Turner, Helen C; Brenner, David J; Chen, Youhua; Bertucci, Antonella; Zhang, Jian; Wang, Hongliang; Lyulko, Oleksandra V; Xu, Yanping; Shuryak, Igor; Schaefer, Julia; Simaan, Nabil; Randers-Pehrson, Gerhard; Yao, Y Lawrence; Amundson, Sally A; Garty, Guy

2011-03-01

The immunofluorescence-based detection of γ-H2AX is a reliable and sensitive method for quantitatively measuring DNA double-strand breaks (DSBs) in irradiated samples. Since H2AX phosphorylation is highly linear with radiation dose, this well-established biomarker is in current use in radiation biodosimetry. At the Center for High-Throughput Minimally Invasive Radiation Biodosimetry, we have developed a fully automated high-throughput system, the RABIT (Rapid Automated Biodosimetry Tool), that can be used to measure γ-H2AX yields from fingerstick-derived samples of blood. The RABIT workstation has been designed to fully automate the γ-H2AX immunocytochemical protocol, from the isolation of human blood lymphocytes in heparin-coated PVC capillaries to the immunolabeling of γ-H2AX protein and image acquisition to determine fluorescence yield. High throughput is achieved through the use of purpose-built robotics, lymphocyte handling in 96-well filter-bottomed plates, and high-speed imaging. The goal of the present study was to optimize and validate the performance of the RABIT system for the reproducible and quantitative detection of γ-H2AX total fluorescence in lymphocytes in a multiwell format. Validation of our biodosimetry platform was achieved by the linear detection of a dose-dependent increase in γ-H2AX fluorescence in peripheral blood samples irradiated ex vivo with γ rays over the range 0 to 8 Gy. This study demonstrates for the first time the optimization and use of our robotically based biodosimetry workstation to successfully quantify γ-H2AX total fluorescence in irradiated peripheral lymphocytes.

Does the Effort of Processing Potential Incentives Influence the Adaption of Context Updating in Older Adults?

PubMed Central

Schmitt, Hannah; Kray, Jutta; Ferdinand, Nicola K.

2017-01-01

A number of aging studies suggest that older adults process positive and negative information differently. For instance, the socioemotional selectivity theory postulates that older adults preferably process positive information in service of emotional well-being (Reed and Carstensen, 2012). Moreover, recent research has started to investigate whether incentives like gains or losses can influence cognitive control in an ongoing task. In an earlier study (Schmitt et al., 2015), we examined whether incentive cues, indicating potential monetary gains, losses, or neutral outcomes for good performance in the following trial, would influence older adults’ ability to exert cognitive control. Cognitive control was measured in an AX-Continuous-Performance-Task (AX-CPT) in which participants had to select their responses to probe stimuli depending on a preceding context cue. In this study, we did not find support for a positivity effect in older adults, but both gains and losses led to enhanced context processing. As the trial-wise presentation mode may be too demanding on cognitive resources for such a bias to occur, the main goal of the present study was to examine whether motivational mindsets, induced by block-wise presentation of incentives, would result in a positivity effect. For this reason, we examined 17 older participants (65–76 years) in the AX-CPT using a block-wise presentation of incentive cues and compared them to 18 older adults (69–78 years) with the trial-wise presentation mode from our earlier study (Schmitt et al., 2015). Event-related potentials were recorded to the onset of the motivational cue and during the AX-CPT. Our results show that (a) older adults initially process cues signaling potential losses more strongly, but later during the AX-CPT invest more cognitive resources in preparatory processes like context updating in conditions with potential gains, and (b) block-wise and trial-wise presentation of incentive cues differentially influenced cognitive control. When incentives were presented block-wise, the above described valence effects were consistently found. In contrast, when incentives were presented trial-wise, the effects were mixed and salience as well as valence effects can be obtained. Hence, how positive and negative incentive cues influence cognitive control in older adults is dependent on demands of cue processing. PMID:29170649

Does the Effort of Processing Potential Incentives Influence the Adaption of Context Updating in Older Adults?

PubMed

Schmitt, Hannah; Kray, Jutta; Ferdinand, Nicola K

2017-01-01

A number of aging studies suggest that older adults process positive and negative information differently. For instance, the socioemotional selectivity theory postulates that older adults preferably process positive information in service of emotional well-being (Reed and Carstensen, 2012). Moreover, recent research has started to investigate whether incentives like gains or losses can influence cognitive control in an ongoing task. In an earlier study (Schmitt et al., 2015), we examined whether incentive cues, indicating potential monetary gains, losses, or neutral outcomes for good performance in the following trial, would influence older adults' ability to exert cognitive control. Cognitive control was measured in an AX-Continuous-Performance-Task (AX-CPT) in which participants had to select their responses to probe stimuli depending on a preceding context cue. In this study, we did not find support for a positivity effect in older adults, but both gains and losses led to enhanced context processing. As the trial-wise presentation mode may be too demanding on cognitive resources for such a bias to occur, the main goal of the present study was to examine whether motivational mindsets, induced by block-wise presentation of incentives, would result in a positivity effect. For this reason, we examined 17 older participants (65-76 years) in the AX-CPT using a block-wise presentation of incentive cues and compared them to 18 older adults (69-78 years) with the trial-wise presentation mode from our earlier study (Schmitt et al., 2015). Event-related potentials were recorded to the onset of the motivational cue and during the AX-CPT. Our results show that (a) older adults initially process cues signaling potential losses more strongly, but later during the AX-CPT invest more cognitive resources in preparatory processes like context updating in conditions with potential gains, and (b) block-wise and trial-wise presentation of incentive cues differentially influenced cognitive control. When incentives were presented block-wise, the above described valence effects were consistently found. In contrast, when incentives were presented trial-wise, the effects were mixed and salience as well as valence effects can be obtained. Hence, how positive and negative incentive cues influence cognitive control in older adults is dependent on demands of cue processing.

Selective immediate responders to amoxicillin and clavulanic acid tolerate penicillin derivative administration after confirming the diagnosis.

PubMed

Blanca-Lopez, N; Perez-Alzate, D; Ruano, F; Garcimartin, M; de la Torre, V; Mayorga, C; Somoza, M L; Perkins, J; Blanca, M; Canto, M G; Torres, M J

2015-08-01

An increasing number of patients show immediate selective hypersensitivity reactions to clavulanic acid (CLV) and amoxicillin (AX), probably due to their increased prescription. The maintenance of this response should be established. To assess that the immediate hypersensitivity selective response to AX or to CLV is maintained after repeated administration of penicillin G (PG)/penicillin V (PV) and AX. Patients with proven immediate hypersensitivity to AX (Group A) or CLV (Group B) were included. Diagnosis was performed using skin tests with major and minor determinants of PG (PPL/MDM), AX and CLV and by drug provocation test (DPT) if required. Selectivity was established by confirming tolerance to PG/PV (Group A) and to PG/PV and AX (Group B). The maintenance of the selective response was verified by repeating DPT, 15 days after the initial investigation, with the same procedure. Of 51 patients, 78% belonged to Group A and 22% to Group B. Most had anaphylaxis. In Group A, 72% were skin test positive; 28% required DPT. In Group B, 63% were skin test positive; 37% required DPT. Only two AX-selective cases developed positive responses after re-provocation with PG/PV. No cases selective for CLV developed a positive response to PG, PV or AX. The selective response to AX appears consistent, and a response to penicillin determinants only develops in a minority of cases. For the case of CLV, the selective response appears not to be modified by exposure to penicillin determinants, meaning that patients with CLV allergy can take penicillin derivatives safely. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Monkey Prefrontal Neurons Reflect Logical Operations for Cognitive Control in a Variant of the AX Continuous Performance Task (AX-CPT)

PubMed Central

Blackman, Rachael K.; Crowe, David A.; DeNicola, Adele L.; Sakellaridi, Sofia; MacDonald, Angus W.

2016-01-01

Cognitive control is the ability to modify the behavioral response to a stimulus based on internal representations of goals or rules. We sought to characterize neural mechanisms in prefrontal cortex associated with cognitive control in a context that would maximize the potential for future translational relevance to human neuropsychiatric disease. To that end, we trained monkeys to perform a dot-pattern variant of the AX continuous performance task that is used to measure cognitive control impairment in patients with schizophrenia (MacDonald, 2008; Jones et al., 2010). Here we describe how information processing for cognitive control in this task is related to neural activity patterns in prefrontal cortex of monkeys, to advance our understanding of how behavioral flexibility is implemented by prefrontal neurons in general, and to model neural signals in the healthy brain that may be disrupted to produce cognitive control deficits in schizophrenia. We found that the neural representation of stimuli in prefrontal cortex is strongly biased toward stimuli that inhibit prepotent or automatic responses. We also found that population signals encoding different stimuli were modulated to overlap in time specifically in the case that information from multiple stimuli had to be integrated to select a conditional response. Finally, population signals relating to the motor response were biased toward less frequent and therefore less automatic actions. These data relate neuronal activity patterns in prefrontal cortex to logical information processing operations required for cognitive control, and they characterize neural events that may be disrupted in schizophrenia. SIGNIFICANCE STATEMENT Functional imaging studies have demonstrated that cognitive control deficits in schizophrenia are associated with reduced activation of the dorsolateral prefrontal cortex (MacDonald et al., 2005). However, these data do not reveal how the disease has disrupted the function of prefrontal neurons to produce the observed deficits in cognitive control. Relating cognitive control to neurophysiological signals at a cellular level in prefrontal cortex is a necessary first step toward understanding how disruption of these signals could lead to cognitive control failure in neuropsychiatric disease. To that end, we translated a task that measures cognitive control deficits in patients with schizophrenia to monkeys and describe here how neural signals in prefrontal cortex relate to performance. PMID:27053213

Impaired Midline Theta Power and Connectivity During Proactive Cognitive Control in Schizophrenia.

PubMed

Ryman, Sephira G; Cavanagh, James F; Wertz, Christopher J; Shaff, Nicholas A; Dodd, Andrew B; Stevens, Brigitte; Ling, Josef; Yeo, Ronald A; Hanlon, Faith M; Bustillo, Juan; Stromberg, Shannon F; Lin, Denise S; Abrams, Swala; Mayer, Andrew R

2018-05-25

Disrupted proactive cognitive control, a form of early selection and active goal maintenance, is hypothesized to underlie the broad cognitive deficits observed in patients with schizophrenia (SPs). Current research suggests that the disrupted activation within and connectivity between regions of the cognitive control network contribute to disrupted proactive cognitive control; however, no study has examined these mechanisms using an AX Continuous Performance Test task in schizophrenia. Twenty-six SPs (17 male subjects; mean age 34.46 ± 8.77 years) and 28 healthy control participants (HCs; 16 male subjects; mean age 31.43 ± 7.23 years) underwent an electroencephalogram while performing the AX Continuous Performance Test. To examine the extent of activation and level of connectivity within the cognitive control network, power, intertrial phase clustering, and intersite phase clustering metrics were calculated and analyzed. SPs exhibited expected general decrements in behavioral performance relative to HCs and a more selective deficit in conditions requiring proactive cognitive control. Additionally, SPs exhibited deficits in midline theta power and connectivity during proactive cognitive control trials. Specifically, HCs exhibited significantly greater theta power for B cues relative to A cues, whereas SPs exhibited no significant differences between A- and B-cue theta power. Additionally, differential theta connectivity patterns were observed in SPs and HCs. Behavioral measures of proactive cognitive control predicted functional outcomes in SPs. This study suggests that low-frequency midline theta activity is selectively disrupted during proactive cognitive control in SPs. The disrupted midline theta activity may reflect a failure of SPs to proactively recruit cognitive control processes. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Ingestion of a novel galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex affected growth performance and fermentative and immunological characteristics of broiler chicks challenged with Salmonella typhimurium

USDA-ARS?s Scientific Manuscript database

Fermentable carbohydrates may enhance the ability of the gastrointestinal tract to defend against a pathogenic infection. We hypothesized that a galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex would positively impact immune status and prevent colonization and shedding in Salmonell...

Assessment of axillary temperature for the evaluation of normal body temperature of healthy young adults at rest in a thermoneutral environment.

PubMed

Marui, Shuri; Misawa, Ayaka; Tanaka, Yuki; Nagashima, Kei

2017-02-22

The aims of this study were to (1) evaluate whether recently introduced methods of measuring axillary temperature are reliable, (2) examine if individuals know their baseline body temperature based on an actual measurement, and (3) assess the factors affecting axillary temperature and reevaluate the meaning of the axillary temperature. Subjects were healthy young men and women (n = 76 and n = 65, respectively). Three measurements were obtained: (1) axillary temperature using a digital thermometer in a predictive mode requiring 10 s (T ax-10 s ), (2) axillary temperature using a digital thermometer in a standard mode requiring 10 min (T ax-10 min ), and (3) tympanic membrane temperature continuously measured by infrared thermometry (T ty ). The subjects answered questions about eating and exercise habits, sleep and menstrual cycles, and thermoregulation and reported what they believed their regular body temperature to be (T reg ). T reg , T ax-10 s , T ax-10 min , and T ty were 36.2 ± 0.4, 36.4 ± 0.5, 36.5 ± 0.4, and 36.8 ± 0.3 °C (mean ± SD), respectively. There were correlations between T ty and T ax-10 min , T ty and T ax-10 s , and T ax-10 min and T ax-10 s (r = .62, r = .46, and r = .59, respectively, P < .001), but not between T reg and T ax-10 s (r = .11, P = .20). A lower T ax-10 s was associated with smaller body mass indices and irregular menstrual cycles. Modern devices for measuring axillary temperature may have changed the range of body temperature that is recognized as normal. Core body temperature variations estimated by tympanic measurements were smaller than those estimated by axillary measurements. This variation of axillary temperature may be due to changes in the measurement methods introduced by modern devices and techniques. However, axillary temperature values correlated well with those of tympanic measurements, suggesting that the technique may reliably report an individual's state of health. It is important for individuals to know their baseline axillary temperature to evaluate subsequent temperature measurements as normal or abnormal. Moreover, axillary temperature variations may, in part, reflect fat mass and changes due to the menstrual cycle.

Increased γ-H2A.X intensity in response to chronic medium-dose-rate γ-ray irradiation.

PubMed

Sugihara, Takashi; Murano, Hayato; Tanaka, Kimio

2012-01-01

The molecular mechanisms of DNA repair following chronic medium-dose-rate (MDR) γ-ray-induced damage remain largely unknown. We used a cell function imager to quantitatively measure the fluorescence intensity of γ-H2A.X foci in MDR (0.015 Gy/h and 0.06 Gy/h) or high-dose-rate (HDR) (54 Gy/h) γ-ray irradiated embryonic fibroblasts derived from DNA-dependent protein kinase mutated mice (scid/scid mouse embryonic fibroblasts (scid/scid MEFs)). The obtained results are as follows: (1) Automatic measurement of the intensity of radiation-induced γ-H2A.X foci by the cell function imager provides more accurate results compared to manual counting of γ-H2A.X foci. (2) In high-dose-rate (HDR) irradiation, γ-H2A.X foci with high fluorescence intensity were observed at 1 h after irradiation in both scid/scid and wild-type MEFs. These foci were gradually reduced through de-phosphorylation at 24 h or 72 h after irradiation. Furthermore, the fluorescence intensity at 24 h increased to a significantly greater extent in scid/scid MEFs than in wild-type MEFs in the G(1) phase, although no significant difference was observed in G(2)/M-phase MEFs, suggesting that DNA-PKcs might be associated with non-homologous-end-joining-dependent DNA repair in the G(1) phase following HDR γ-ray irradiation. (3) The intensity of γ-H2A.X foci for continuous MDR (0.06 Gy/h and 0.015 Gy/h) irradiation increased significantly and in a dose-dependent fashion. Furthermore, unlike HDR-irradiated scid/scid MEFs, the intensity of γ-H2A.X foci in MDR-irradiated scid/scid MEFs showed no significant increase in the G(1) phase at 24 h, indicating that DNA repair systems using proteins other than DNA-PKcs might induce cell functioning that are subjected to MDR γ-ray irradiation. Our results indicate that the mechanism of phosphorylation or de-phosphorylation of γ-H2A.X foci induced by chronic MDR γ-ray irradiation might be different from those induced by HDR γ-ray irradiation.

Pretreatment of liver grafts in vivo by γ-aminobutyric acid receptor regulation reduces cold ischemia/warm reperfusion injury in rat

PubMed Central

Hori, Tomohide; Gardner, Lindsay B.; Hata, Toshiyuki; Chen, Feng; Baine, Ann-Marie T.; Uemoto, Shinji; Nguyen, Justin H.

2014-01-01

Summary Background: Gamma-aminobutyric acid (GABA) is found throughout the body. The regulation of GABA receptor (GABAR) reduces oxidative stress (OS). Ischemia/reperfusion injury after orthotopic liver transplantation (OLT) causes OS-induced graft damage. The effects of GABAR regulation in donors in vivo were investigated. Material/Methods: Donor rats received saline, a GABAR agonist or GABAR antagonist 4 h before surgery. Recipient rats were divided into four groups according to the donor treatments: laparotomy, OLT with saline, OLT with GABAR agonist and OLT with GABAR antagonist. Histopathological, biochemical and immunohistological examinations were performed at 6, 12 and 24 h after OLT. Protein assays were performed at 6 h after OLT. The 4-hydroxynonenal (4-HNE), ataxia-telangiectasia mutated kinase (ATM), phosphorylated histone H2AX (γH2AX), phosphatidylinositol-3 kinase (PI3K), Akt and superoxide dismutase (SOD) were assessed by western blot analysis. Results: In the univariate analysis, histopathological and biochemical profiles verified that the GABAR agonist reduced graft damage. Immunohistology revealed that the GABAR agonist prevented the induction of apoptosis. Measurement of 4-4-HNE levels confirmed OS-induced damage after OLT, and the GABAR agonist improved this damage. In the γH2AX, PI3K, Akt and antioxidant enzymes (SODs), ATM and H2AX were greatly increased after OLT, and were reduced by the GABAR agonist. In the multivariate analyses between multiple groups, histopathological assessment, aspartate aminotransferase level, immunohistological examinations for apoptotic induction and γH2AX showed statistical differences. Conclusions: A specific agonist demonstrated regulation of GABAR in vivo in the liver. This activation in vivo reduced OS after OLT via the ATM/H2AX pathway. PMID:23792534

Effect of an oxygenating agent on oral bacteria in vitro and on dental plaque composition in healthy young adults.

PubMed

Fernandez y Mostajo, Mercedes; van der Reijden, Wil A; Buijs, Mark J; Beertsen, Wouter; Van der Weijden, Fridus; Crielaard, Wim; Zaura, Egija

2014-01-01

Oral bacteria live in symbiosis with the host. Therefore, when mouthwashes are indicated, selective inhibition of taxa contributing to disease is preferred instead of broad-spectrum antimicrobials. The potential selectivity of an oxygenating mouthwash, Ardox-X® (AX), has not been assessed. The aim of this study was to determine the antimicrobial potential of AX and the effects of a twice-daily oral rinse on dental plaque composition. In vitro, 16 oral bacterial strains were tested using agar diffusion susceptibility, minimum inhibitory and minimum bactericidal concentration tests. A pilot clinical study was performed with 25 healthy volunteers. Clinical assessments and microbiological sampling of supragingival plaque were performed at 1 month before the experiment (Pre-exp), at the start of the experiment (Baseline) and after the one-week experimental period (Post-exp). During the experiment individuals used AX mouthwash twice daily in absence of other oral hygiene measures. The microbiological composition of plaque was assessed by 16S rRNA gene amplicon sequencing. AX showed high inter-species variation in microbial growth inhibition. The tested Prevotella strains and Fusobacterium nucleatum showed the highest sensitivity, while streptococci and Lactobacillus acidophilus were most resistant to AX. Plaque scores at Pre-exp and Baseline visits did not differ significantly (p = 0.193), nor did the microbial composition of plaque. During a period of 7-days non-brushing but twice daily rinsing plaque scores increased from 2.21 (0.31) at Baseline to 2.43 (0.39) Post-exp. A significant microbial shift in composition was observed: genus Streptococcus and Veillonella increased while Corynebacterium, Haemophilus, Leptotrichia, Cardiobacterium and Capnocytophaga decreased (p ≤ 0.001). AX has the potential for selective inhibition of oral bacteria. The shift in oral microbiome after 1 week of rinsing deserves further research.

Ingestion of a novel galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex affected growth performance and fermentative and immunological characteristics of broiler chicks challenged with Salmonella typhimurium1

USDA-ARS?s Scientific Manuscript database

Fermentable carbohydrates may enhance the ability of the gastrointestinal tract to defend against a pathogenic infection. We hypothesized that a galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex would positively impact immune status and prevent colonization and shedding in Salmonell...

Equivalent Vectors

ERIC Educational Resources Information Center

Levine, Robert

2004-01-01

The cross-product is a mathematical operation that is performed between two 3-dimensional vectors. The result is a vector that is orthogonal or perpendicular to both of them. Learning about this for the first time while taking Calculus-III, the class was taught that if AxB = AxC, it does not necessarily follow that B = C. This seemed baffling. The…

High plasticity of axonal pathology in Alzheimer's disease mouse models.

PubMed

Blazquez-Llorca, Lidia; Valero-Freitag, Susana; Rodrigues, Eva Ferreira; Merchán-Pérez, Ángel; Rodríguez, J Rodrigo; Dorostkar, Mario M; DeFelipe, Javier; Herms, Jochen

2017-02-07

Axonal dystrophies (AxDs) are swollen and tortuous neuronal processes that are associated with extracellular depositions of amyloid β (Aβ) and have been observed to contribute to synaptic alterations occurring in Alzheimer's disease. Understanding the temporal course of this axonal pathology is of high relevance to comprehend the progression of the disease over time. We performed a long-term in vivo study (up to 210 days of two-photon imaging) with two transgenic mouse models (dE9xGFP-M and APP-PS1xGFP-M). Interestingly, AxDs were formed only in a quarter of GFP-expressing axons near Aβ-plaques, which indicates a selective vulnerability. AxDs, especially those reaching larger sizes, had long lifetimes and appeared as highly plastic structures with large variations in size and shape and axonal sprouting over time. In the case of the APP-PS1 mouse only, the formation of new long axonal segments in dystrophic axons (re-growth phenomenon) was observed. Moreover, new AxDs could appear at the same point of the axon where a previous AxD had been located before disappearance (re-formation phenomenon). In addition, we observed that most AxDs were formed and developed during the imaging period, and numerous AxDs had already disappeared by the end of this time. This work is the first in vivo study analyzing quantitatively the high plasticity of the axonal pathology around Aβ plaques. We hypothesized that a therapeutically early prevention of Aβ plaque formation or their growth might halt disease progression and promote functional axon regeneration and the recovery of neural circuits.

Performance of the ASAS classification criteria for axial and peripheral spondyloarthritis: a systematic literature review and meta-analysis.

PubMed

Sepriano, Alexandre; Rubio, Roxana; Ramiro, Sofia; Landewé, Robert; van der Heijde, Désirée

2017-05-01

To summarise the evidence on the performance of the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA) (also imaging and clinical arm separately), peripheral (p)SpA and the entire set, when tested against the rheumatologist's diagnosis ('reference standard'). A systematic literature review was performed to identify eligible studies. Raw data on SpA diagnosis and classification were extracted or, if necessary, obtained from the authors of the selected publications. A meta-analysis was performed to obtain pooled estimates for sensitivity, specificity, positive and negative likelihood ratios, by fitting random effects models. Nine papers fulfilled the inclusion criteria (N=5739 patients). The entire set of the ASAS SpA criteria yielded a high pooled sensitivity (73%) and specificity (88%). Similarly, good results were found for the axSpA criteria (sensitivity: 82%; specificity: 88%). Splitting the axSpA criteria in 'imaging arm only' and 'clinical arm only' resulted in much lower sensitivity (30% and 23% respectively), but very high specificity was retained (97% and 94% respectively). The pSpA criteria were less often tested than the axSpA criteria and showed a similarly high pooled specificity (87%) but lower sensitivity (63%). Accumulated evidence from studies with more than 5500 patients confirms the good performance of the various ASAS SpA criteria as tested against the rheumatologist's diagnosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Increased γ-H2A.X Intensity in Response to Chronic Medium-Dose-Rate γ-Ray Irradiation

PubMed Central

Sugihara, Takashi; Murano, Hayato; Tanaka, Kimio

2012-01-01

Background The molecular mechanisms of DNA repair following chronic medium-dose-rate (MDR) γ-ray-induced damage remain largely unknown. Methodology/Principal Findings We used a cell function imager to quantitatively measure the fluorescence intensity of γ-H2A.X foci in MDR (0.015 Gy/h and 0.06 Gy/h) or high-dose-rate (HDR) (54 Gy/h) γ-ray irradiated embryonic fibroblasts derived from DNA-dependent protein kinase mutated mice (scid/scid mouse embryonic fibroblasts (scid/scid MEFs)). The obtained results are as follows: (1) Automatic measurement of the intensity of radiation-induced γ-H2A.X foci by the cell function imager provides more accurate results compared to manual counting of γ-H2A.X foci. (2) In high-dose-rate (HDR) irradiation, γ-H2A.X foci with high fluorescence intensity were observed at 1 h after irradiation in both scid/scid and wild-type MEFs. These foci were gradually reduced through de-phosphorylation at 24 h or 72 h after irradiation. Furthermore, the fluorescence intensity at 24 h increased to a significantly greater extent in scid/scid MEFs than in wild-type MEFs in the G1 phase, although no significant difference was observed in G2/M-phase MEFs, suggesting that DNA-PKcs might be associated with non-homologous-end-joining-dependent DNA repair in the G1 phase following HDR γ-ray irradiation. (3) The intensity of γ-H2A.X foci for continuous MDR (0.06 Gy/h and 0.015 Gy/h) irradiation increased significantly and in a dose-dependent fashion. Furthermore, unlike HDR-irradiated scid/scid MEFs, the intensity of γ-H2A.X foci in MDR-irradiated scid/scid MEFs showed no significant increase in the G1 phase at 24 h, indicating that DNA repair systems using proteins other than DNA-PKcs might induce cell functioning that are subjected to MDR γ-ray irradiation. Conclusions Our results indicate that the mechanism of phosphorylation or de-phosphorylation of γ-H2A.X foci induced by chronic MDR γ-ray irradiation might be different from those induced by HDR γ-ray irradiation. PMID:23028931

Aberrant astrocyte Ca2+ signals "AxCa signals" exacerbate pathological alterations in an Alexander disease model.

PubMed

Saito, Kozo; Shigetomi, Eiji; Yasuda, Rei; Sato, Ryuichi; Nakano, Masakazu; Tashiro, Kei; Tanaka, Kenji F; Ikenaka, Kazuhiro; Mikoshiba, Katsuhiko; Mizuta, Ikuko; Yoshida, Tomokatsu; Nakagawa, Masanori; Mizuno, Toshiki; Koizumi, Schuichi

2018-05-01

Alexander disease (AxD) is a rare neurodegenerative disorder caused by gain of function mutations in the glial fibrillary acidic protein (GFAP) gene. Accumulation of GFAP proteins and formation of Rosenthal fibers (RFs) in astrocytes are hallmarks of AxD. However, malfunction of astrocytes in the AxD brain is poorly understood. Here, we show aberrant Ca 2+ responses in astrocytes as playing a causative role in AxD. Transcriptome analysis of astrocytes from a model of AxD showed age-dependent upregulation of GFAP, several markers for neurotoxic reactive astrocytes, and downregulation of Ca 2+ homeostasis molecules. In situ AxD model astrocytes produced aberrant extra-large Ca 2+ signals "AxCa signals", which increased with age, correlated with GFAP upregulation, and were dependent on stored Ca 2+ . Inhibition of AxCa signals by deletion of inositol 1,4,5-trisphosphate type 2 receptors (IP3R2) ameliorated AxD pathogenesis. Taken together, AxCa signals in the model astrocytes would contribute to AxD pathogenesis. © 2018 Wiley Periodicals, Inc.

IDENTIFICATION OF A POPULATION OF X-RAY-EMITTING MASSIVE STARS IN THE GALACTIC PLANE

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

Anderson, Gemma E.; Gaensler, B. M.; Kaplan, David L.

2011-02-01

We present X-ray, infrared, optical, and radio observations of four previously unidentified Galactic plane X-ray sources: AX J163252-4746, AX J184738-0156, AX J144701-5919, and AX J144547-5931. Detection of each source with the Chandra X-ray Observatory has provided sub-arcsecond localizations, which we use to identify bright infrared counterparts to all four objects. Infrared and optical spectroscopy of these counterparts demonstrate that all four X-ray sources are extremely massive stars, with spectral classifications: Ofpe/WN9 (AX J163252-4746), WN7 (AX J184738-0156 = WR121a), WN7-8h (AX J144701-5919), and OIf{sup +} (AX J144547-5931). AX J163252-4746 and AX J184738-0156 are both luminous, hard, X-ray emitters with strong Femore » XXV emission lines in their X-ray spectra at {approx}6.7 keV. The multi-wavelength properties of AX J163252-4746 and AX J184738-0156 are not consistent with isolated massive stars or accretion onto a compact companion; we conclude that their X-ray emission is most likely generated in a colliding-wind binary (CWB) system. For both AX J144701-5919 and AX J144547-5931, the X-ray emission is an order of magnitude less luminous and with a softer spectrum. These properties are consistent with a CWB interpretation for these two sources also, but other mechanisms for the generation of X-rays cannot be excluded. There are many other as yet unidentified X-ray sources in the Galactic plane, with X-ray properties similar to those seen for AX J163252-4746, AX J184738-0156, AX J144701-5919, and AX J144547-5931. This may indicate a substantial population of X-ray-emitting massive stars and CWBs in the Milky Way.« less

Molecular Features of Wheat Endosperm Arabinoxylan Inclusion in Functional Bread

PubMed Central

Li, Weili; Hu, Hui; Wang, Qi; Brennan, Charles J.

2013-01-01

Arabinoxylan (AX) is a major dietary fibre component found in a variety of cereals. Numerous health benefits of arabinoxylans have been reported to be associated with their solubility and molecular features. The current study reports the development of a functional bread using a combination of AX-enriched material (AEM) and optimal commercial endoxylanase. The total AX content of bread was increased to 8.2 g per 100 g available carbohydrates. The extractability of AX in breads with and without endoxylanase was determined. The results demonstrate that water-extractable AX (WE-AX) increased progressively through the bread making process. The application of endoxylanase also increased WE-AX content. The presence of 360 ppm of endoxylanase had positive effects on the bread characteristics in terms of bread volume and firmness by converting the water unextractable (WU)-AX to WE-AX. In addition, the molecular weight (Mw) distribution of the WE-AX of bread with and without endoxylanase was characterized by size-exclusion chromatography. The results show that as the portion of WE-AX increased, the amount of high Mw WE-AX (higher than 100 kDa) decreased, whereas the amount of low Mw WE-AX (lower than 100 kDa) increased from 33.2% to 44.2% through the baking process. The low Mw WE-AX further increased to 75.5% with the application of the optimal endoxylanase (360 ppm). PMID:28239111

Effect of an oxygenating agent on oral bacteria in vitro and on dental plaque composition in healthy young adults

PubMed Central

Fernandez y Mostajo, Mercedes; van der Reijden, Wil A.; Buijs, Mark J.; Beertsen, Wouter; van der Weijden, Fridus; Crielaard, Wim; Zaura, Egija

2014-01-01

Oral bacteria live in symbiosis with the host. Therefore, when mouthwashes are indicated, selective inhibition of taxa contributing to disease is preferred instead of broad-spectrum antimicrobials. The potential selectivity of an oxygenating mouthwash, Ardox-X® (AX), has not been assessed. The aim of this study was to determine the antimicrobial potential of AX and the effects of a twice-daily oral rinse on dental plaque composition. Material and methods: In vitro, 16 oral bacterial strains were tested using agar diffusion susceptibility, minimum inhibitory and minimum bactericidal concentration tests. A pilot clinical study was performed with 25 healthy volunteers. Clinical assessments and microbiological sampling of supragingival plaque were performed at 1 month before the experiment (Pre-exp), at the start of the experiment (Baseline) and after the one-week experimental period (Post-exp). During the experiment individuals used AX mouthwash twice daily in absence of other oral hygiene measures. The microbiological composition of plaque was assessed by 16S rRNA gene amplicon sequencing. Results: AX showed high inter-species variation in microbial growth inhibition. The tested Prevotella strains and Fusobacterium nucleatum showed the highest sensitivity, while streptococci and Lactobacillus acidophilus were most resistant to AX. Plaque scores at Pre-exp and Baseline visits did not differ significantly (p = 0.193), nor did the microbial composition of plaque. During a period of 7-days non-brushing but twice daily rinsing plaque scores increased from 2.21 (0.31) at Baseline to 2.43 (0.39) Post-exp. A significant microbial shift in composition was observed: genus Streptococcus and Veillonella increased while Corynebacterium, Haemophilus, Leptotrichia, Cardiobacterium and Capnocytophaga decreased (p ≤ 0.001). Conclusion: AX has the potential for selective inhibition of oral bacteria. The shift in oral microbiome after 1 week of rinsing deserves further research. PMID:25101249

Thermoregulatory responses of rhesus monkeys during spaceflight

NASA Technical Reports Server (NTRS)

Sulzman, F. M.; Ferraro, J. S.; Fuller, C. A.; Moore-Ede, M. C.; Klimovitsky, V.; Magedov, V.; Alpatov, A. M.

1992-01-01

This study examines the activity, axillary temperature (T(ax)), and ankle skin temperature (Tsk) of two male Rhesus monkeys exposed to microgravity in space. The animals were flown on a Soviet biosatellite mission (COSMOS 1514). Measurements on the flight animals, as well as synchronous flight controls, were performed in the Soviet Union. Additional control studies were performed in the United States to examine the possible role of metabolic heat production in the T(ax) response observed during the spaceflight. All monkeys were exposed to a 24-h light-dark cycle (LD 16:8) throughout these studies. During weightlessness, T(ax) in both flight animals was lower than on earth. The largest difference (0.75 degree C) occurred during the night. There was a reduction in mean heart rate and Tsk during flight. This suggests a reduction in both heat loss and metabolic rate during spaceflight. Although the circadian rhythms in all variables were present during flight, some differences were noted. For example, the amplitude of the rhythms in Tsk and activity were attenuated. Furthermore, the T(ax) and activity rhythms did not have precise 24.0 hour periods and may have been externally desynchronized from the 24-h LD cycle. These data suggest a weakening of the coupling between the internal circadian pacemaker and the external LD synchronizer.

Monosodium urate crystal deposition associated with the progress of radiographic grade at the sacroiliac joint in axial SpA: a dual-energy CT study.

PubMed

Zhu, Junqing; Li, Aiwu; Jia, Ertao; Zhou, Yi; Xu, Juan; Chen, Shixian; Huang, Yinger; Xiao, Xiang; Li, Juan

2017-05-02

Previous studies have revealed that ankylosing spondylitis (AS), as the progenitor of axial spondyloarthritis (AxSpA), has been characterized by the insidiously progressive nature of sacroiliitis and spondylitis. Dual-energy computed tomography (DECT) has recently been used to analyse the deposition of monosodium urate (MSU) crystals with higher sensitivity and specificity. However, it remains unclear whether the existence of the MSU crystal deposition detected by DECT at the sacroiliac joint in patients with AxSpA also is associated with the existing structural damage. Here, we performed this study to show the DECT MSU crystal deposits in AxSpA patients without coexisting gout and to ascertain the relationship between the MSU crystal deposition and the structural joint damage of sacroiliac joints. One hundred and eighty-six AxSpA patients without coexisting gout were recruited. The plain radiographs of the sacroiliac joint were obtained, along with the DECT scans at the pelvis and the clinical variables. All statistics based on the left or right sacroiliac joint damage grading (0-4) were calculated independently. Bivariate analysis and ordinal logistic regression was performed between the clinical features and radiographic grades at the sacroiliac joint. At the pelvis, large quantities of MSU crystal deposition were found in patients with AxSpA. The average MSU crystal volume at the left sacroiliac joint, the right sacroiliac joint, and the pelvis were 0.902 ± 1.345, 1.074 ± 1.878, and 5.272 ± 9.044 cm 3 , values which were correlated with serum uric acid concentrations (r = 0.727, 0.740, 0.896; p < 0.001). In bivariate analysis, wide clinical variables were associated with the changes in sacroiliac joint damage. Further, the AxSpA duration, BASFI score, and the volume of MSU crystal at both sides of sacroiliac joint were associated with the progress of radiographic grade at the sacroiliac joints in the ordinal logistic models (left AOR = 1.180, 3.800, 1.920; right AOR = 1.190, 3.034, 1.418; p < 0.01). Large quantities of MSU crystal deposition detected by DECT were found at the pelvis in AxSpA patients without coexisting gout. In addition to AxSpA duration and BASFI score, the MSU crystal deposition at the sacroiliac joint is associated with the progress of radiographic grade at sacroiliac joints in those patients.

Reduced Electromyographic Fatigue Threshold after Performing a Cognitive Fatiguing Task.

PubMed

Ferris, Justine R; Tomlinson, Mary A; Ward, Tayler N; Pepin, Marie E; Malek, Moh H

2018-02-22

Cognitive fatigue tasks performed prior to exercise may reduce exercise capacity. The electromyographic fatigue threshold (EMGFT) is the highest exercise intensity that can be maintained without significant increase in the EMG amplitude versus time relationship. To date, no studies have examined the effect of cognitive fatigue on the estimation of the EMGFT. The purpose of this study, therefore, was to determine whether or not cognitive fatigue prior to performing exercise reduces the estimated EMGFT. Eight healthy college-aged men were recruited from a university student population and visited the laboratory on multiple occasions. In a randomized order, subjects performed either the cognitive fatigue task (AX Continuous Performance Test; AX-CPT) for 60 min on one visit (experimental condition) or watched a video on trains for 60 min on the other visit (control condition). After each condition, subjects performed the incremental single-leg knee-extensor ergometry test while the EMG amplitude was recorded from the rectus femoris muscle and heart rate was monitored throughout. Thereafter, the EMGFT was calculated for each participant for each visit and compared using paired samples t-test. For exercise outcomes, there were no significant mean differences for maximal power output between the two conditions (control: 51 ± 5 vs. fatigue: 50 ± 3 W), but a significant decrease in EMGFT between the two conditions (control: 31 ± 3 vs. fatigue: 24 ± 2 W; p = 0.013). Moreover, maximal heart rate was significantly different between the two conditions (control: 151 ± 5 vs. fatigue: 132 ± 6; p = 0.027). These results suggest that performing the cognitive fatiguing task reduces the EMGFT with a corresponding reduction in maximal heart rate response.

Ectopic expression of H2AX protein promotes TrkA-induced cell death via modulation of TrkA tyrosine-490 phosphorylation and JNK activity upon DNA damage

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

Jung, Eun Joo; Kim, Deok Ryong, E-mail: drkim@gnu.ac.kr

2011-01-21

Research highlights: {yields} We established TrkA-inducible U2OS cells stably expressing GFP-H2AX proteins. {yields} GFP-H2AX was colocalized with TrkA in the cytoplasm. {yields} {gamma}H2AX production was significantly increased upon activation of TrkA and suppressed by TrkA inhibitor or JNK inhibitor. {yields} Ectopic expression of H2AX promoted TrkA-mediated cell death through the modulation of TrkA tyrosine-490 phosphorylation and JNK activity upon DNA damage. -- Abstract: We previously reported that TrkA overexpression causes accumulation of {gamma}H2AX proteins in the cytoplasm, subsequently leading to massive cell death in U2OS cells. To further investigate how cytoplasmic H2AX is associated with TrkA-induced cell death, we establishedmore » TrkA-inducible cells stably expressing GFP-tagged H2AX. We found that TrkA co-localizes with ectopically expressed GFP-H2AX proteins in the cytoplasm, especially at the juxta-nuclear membranes, which supports our previous results about a functional connection between TrkA and {gamma}H2AX in TrkA-induced cell death. {gamma}H2AX production from GFP-H2AX proteins was significantly increased when TrkA was overexpressed. Moreover, ectopic expression of H2AX activated TrkA-mediated signal pathways via up-regulation of TrkA tyrosine-490 phosphorylation. In addition, suppression of TrkA tyrosine-490 phosphorylation under a certain condition was removed by ectopic expression of H2AX, indicating a functional role of H2AX in the maintenance of TrkA activity. Indeed, TrkA-induced cell death was highly elevated by ectopic H2AX expression, and it was further accelerated by DNA damage via JNK activation. These all results suggest that cytoplasmic H2AX could play an important role in TrkA-mediated cell death by modulating TrkA upon DNA damage.« less

Induction and Processing of the Radiation-Induced Gamma-H2AX Signal and Its Link to the Underlying Pattern of DSB: A Combined Experimental and Modelling Study

PubMed Central

Tommasino, Francesco; Friedrich, Thomas; Jakob, Burkhard; Meyer, Barbara; Durante, Marco; Scholz, Michael

2015-01-01

We present here an analysis of DSB induction and processing after irradiation with X-rays in an extended dose range based on the use of the γH2AX assay. The study was performed by quantitative flow cytometry measurements, since the use of foci counting would result in reasonable accuracy only in a limited dose range of a few Gy. The experimental data are complemented by a theoretical analysis based on the GLOBLE model. In fact, original aim of the study was to test GLOBLE predictions against new experimental data, in order to contribute to the validation of the model. Specifically, the γH2AX signal kinetics has been investigated up to 24 h after exposure to increasing photon doses between 2 and 500 Gy. The prolonged persistence of the signal at high doses strongly suggests dose dependence in DSB processing after low LET irradiation. Importantly, in the framework of our modelling analysis, this is related to a gradually increased fraction of DSB clustering at the micrometre scale. The parallel study of γH2AX dose response curves shows the onset of a pronounced saturation in two cell lines at a dose of about 20 Gy. This dose is much lower than expected according to model predictions based on the values usually adopted for the DSB induction yield (≈ 30 DSB/Gy) and for the γH2AX foci extension of approximately 2 Mbp around the DSB. We show and discuss how theoretical predictions and experimental findings can be in principle reconciled by combining an increased DSB induction yield with the assumption of a larger genomic extension for the single phosphorylated regions. As an alternative approach, we also considered in our model the possibility of a 3D spreading-mechanism of the H2AX phosphorylation around the induced DSB, and applied it to the analysis of both the aspects considered. Our results are found to be supportive for the basic assumptions on which GLOBLE is built. Apart from giving new insights into the H2AX phosphorylation process, experiments performed at high doses are of relevance in the context of radiation therapy, where hypo-fractionated schemes become increasingly popular. PMID:26067661

Improving the Management of Psoriatic Arthritis and Axial Spondyloarthritis: Roundtable Discussions with Healthcare Professionals and Patients.

PubMed

Garrido-Cumbrera, Marco; Hillmann, Ottfrid; Mahapatra, Raj; Trigos, David; Zajc, Petra; Weiss, Luisa; Bostynets, Galya; Gossec, Laure; Coates, Laura C

2017-12-01

Psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA) are both chronic, inflammatory conditions that result in a substantial burden of disease and reduced quality of life for patients. Patient involvement in developing optimal disease management strategies, including defining appropriate goals, therapies, and treatment options, as well as in setting policy priorities and agendas, is key. A working group of patient organization representatives and rheumatologists explored what patients consider to be unmet needs, important treatment gaps, and future priorities in PsA and AxSpA management. Reducing pain and fatigue, and improving physical and social functioning and work productivity were identified as important treatment goals for patients. Although the major treatment target for both PsA and AxSpA is remission, with low/minimal disease activity an alternative target for patients with established or long-standing disease, the meaning of remission from the patient's perspective needs to be explored further as it may differ considerably from the physician's perspective. Key recommendations from the working group to tackle unmet needs included reducing time to diagnosis, increasing patient and physician disease awareness, focusing on patients' priorities for treatment goals, and improving patient-physician communication. By addressing these key action points moving forward, the hope is that outcomes will continue to improve for patients with PsA and AxSpA.

The Interactive Effects of Transgenically Overexpressed 1Ax1 with Various HMW-GS Combinations on Dough Quality by Introgression of Exogenous Subunits into an Elite Chinese Wheat Variety

PubMed Central

Zhang, Jian; Lei, Qian; Meng, Dandan; Ma, Fengyun; Hu, Wei; Chen, Mingjie; Chang, Junli; Wang, Yuesheng; Yang, Guangxiao; He, Guangyuan

2013-01-01

Seed storage proteins in wheat endosperm, particularly high-molecular-weight glutenin subunits (HMW-GS), are primary determinants of dough properties, and affect both end-use quality and grain utilization of wheat (Triticum aestivum L). In order to investigate the interactive effects between the transgenically overexpressed 1Ax1 subunit with different HMW-GS on dough quality traits, we developed a set of 8 introgression lines (ILs) overexpressing the transgenic HMW-glutenin subunit 1Ax1 by introgression of this transgene from transgenic line B102-1-2/1 into an elite Chinese wheat variety Chuanmai107 (C107), using conventional crossing and backcrossing breeding technique. The donor C107 strain lacks 1Ax1 but contains the HMW-GS pairs 1Dx2+1Dy12 and 1Bx7+1By9. The resultant ILs showed robust and stable expression of 1Ax1 even after five generations of self-pollination, and crossing/backcrossing three times. In addition, overexpression of 1Ax1 was compensated by the endogenous gluten proteins. All ILs exhibited superior agronomic performance when compared to the transgenic parent line, B102-1-2/1. Mixograph results demonstrated that overexpressed 1Ax1 significantly improved dough strength, resistance to extension and over-mixing tolerance, in the targeted wheat cultivar C107. Further, comparisons among the ILs showed the interactive effects of endogenous subunits on dough properties when 1Ax1 was overexpressed: subunit pair 17+18 contributed to increased over-mixing tolerance of the dough; expression of the Glu-D1 allele maintained an appropriate balance between x-type and y-type subunits and thereby improved dough quality. It is consistent with ILs C4 (HMW-GS are 1, 17+18, 2+12) had the highest gluten index and Zeleny sedimentation value. This study demonstrates that wheat quality could be improved by using transgenic wheat overexpressing HMW-GS and the feasibility of using such transgenic lines in wheat quality breeding programs. PMID:24167625

Effect of water migration between arabinoxylans and gluten on baking quality of whole wheat bread detected by magnetic resonance imaging (MRI).

PubMed

Li, Juan; Kang, Ji; Wang, Li; Li, Zhen; Wang, Ren; Chen, Zheng Xing; Hou, Gary G

2012-07-04

A new method, a magnetic resonance imaging (MRI) technique characterized by T(2) relaxation time, was developed to study the water migration mechanism between arabinoxylan (AX) gels and gluten matrix in a whole wheat dough (WWD) system prepared from whole wheat flour (WWF) of different particle sizes. The water sequestration of AX gels in wheat bran was verified by the bran fortification test. The evaluations of baking quality of whole wheat bread (WWB) made from WWF with different particle sizes were performed by using SEM, FT-IR, and RP-HPLC techniques. Results showed that the WWB made from WWF of average particle size of 96.99 μm had better baking quality than those of the breads made from WWF of two other particle sizes, 50.21 and 235.40 μm. T(2) relaxation time testing indicated that the decreased particle size of WWF increased the water absorption of AX gels, which led to water migration from the gluten network to the AX gels and resulted in inferior baking quality of WWB.

Test Results for Caustic Demand Measurements on Tank 241-AX-101 and Tank 241-AX-103 Archive Samples

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

Doll, Stephanie R.; Bolling, Stacie D.

Caustic demand testing is used to determine the necessary amount of caustic required to neutralize species present in the Hanford tank waste and obtain a target molarity of free hydroxide for tank corrosion control. The presence and quantity of hydroxide-consuming analytes are just as important in determining the caustic demand as is the amount of free hydroxide present. No single data point can accurately predict whether a satisfactory hydroxide level is being met, as it is dependent on multiple factors (e.g., free hydroxide, buffers, amphoteric metal hydroxides, bicarbonate, etc.). This enclosure contains the caustic demand, scanning electron microscopy (SEM), polarizedmore » light microscopy (PLM), and X-ray diffraction (XRD) analysis for the tank 241-AX-101 (AX-101) and 241-AX-103 (AX-103) samples. The work was completed to fulfill a customer request outlined in the test plan, WRPS-1505529, “Test Plan and Procedure for Caustic Demand Testing on Tank 241-AX-101 and Tank 241-AX-103 Archive Samples.” The work results will provide a baseline to support planned retrieval of AX-101 and AX-103.« less

Low level phosphorylation of histone H2AX on serine 139 (γH2AX) is not associated with DNA double-strand breaks.

PubMed

Rybak, Paulina; Hoang, Agnieszka; Bujnowicz, Lukasz; Bernas, Tytus; Berniak, Krzysztof; Zarębski, Mirosław; Darzynkiewicz, Zbigniew; Dobrucki, Jerzy

2016-08-02

Phosphorylation of histone H2AX on serine 139 (γH2AX) is an early step in cellular response to a DNA double-strand break (DSB). γH2AX foci are generally regarded as markers of DSBs. A growing body of evidence demonstrates, however, that while induction of DSBs always brings about phosphorylation of histone H2AX, the reverse is not true - the presence of γH2AX foci should not be considered an unequivocal marker of DNA double-strand breaks. We studied DNA damage induced in A549 human lung adenocarcinoma cells by topoisomerase type I and II inhibitors (0.2 μM camptothecin, 10 μM etoposide or 0.2 μM mitoxantrone for 1 h), and using 3D high resolution quantitative confocal microscopy, assessed the number, size and the integrated intensity of immunofluorescence signals of individual γH2AX foci induced by these drugs. Also, investigated was spatial association between γH2AX foci and foci of 53BP1, the protein involved in DSB repair, both in relation to DNA replication sites (factories) as revealed by labeling nascent DNA with EdU. Extensive 3D and correlation data analysis demonstrated that γH2AX foci exhibit a wide range of sizes and levels of H2AX phosphorylation, and correlate differently with 53BP1 and DNA replication. This is the first report showing lack of a link between low level phosphorylation γH2AX sites and double-strand DNA breaks in cells exposed to topoisomerase I or II inhibitors. The data are discussed in terms of mechanisms that may be involved in formation of γH2AX sites of different sizes and intensities.

Differences in behavioural phenotype between parental deletion and maternal uniparental disomy in Prader-Willi syndrome: an ERP study.

PubMed

Stauder, Johannes E A; Boer, Harm; Gerits, Rolf H A; Tummers, Anke; Whittington, Joyce; Curfs, Leopold M G

2005-06-01

Paternal deletion and maternal uniparental disomy are the principal genetic subtypes associated with Prader-Willi syndrome (PWS). Recent clinical findings suggest differences in phenotype between these subtypes. The present experimental study addresses this issue using a cognitive psycho-physiological setup. Behaviour and event-related brain activity (ERP) was recorded by a continuous performance response inhibition task (CPT-AX) in adults with paternal deletion PWS (n=11), maternal uniparental disomy PWS (n=11) and normal controls (n=11). The dependent behavioural variables of the CPT-AX task were reaction time and correct scores. For the ERPs the N200 and P300 components were included which are related to early modality-specific inhibition and late general inhibition, respectively. The disomy group had fewer correct scores and increased reaction times as compared to the CPT-AX task than the control and deletion group. Both PWS subgroups differed significantly from the control group for the N200 amplitude. Only the control group showed the typical task modulation for the N200 amplitude. The amplitude of the P300 component was considerably smaller in the uniparental disomy group than in the deletion and control groups. The ERP results suggest that early modality specific inhibition is impaired in both PWS genetic subtypes. Late general inhibition is impaired in the uniparental disomy group only. Thus, although the ERP data suggests a common impairment in early visual inhibition processing, uniparental disomy and parental deletion genetic PWS subtypes clearly differ in their behavioural and brain activation phenotypes. The present study is the first experimental demonstration which explains the two principal genetic mechanisms that hinder the expression of the genes at 15q11-q13g in PWS result in different behavioural phenotype.

Augmentation of chemokine production by severe acute respiratory syndrome coronavirus 3a/X1 and 7a/X4 proteins through NF-kappaB activation.

PubMed

Kanzawa, Noriyuki; Nishigaki, Kazuo; Hayashi, Takaya; Ishii, Yuichi; Furukawa, Souichi; Niiro, Ayako; Yasui, Fumihiko; Kohara, Michinori; Morita, Kouichi; Matsushima, Kouji; Le, Mai Quynh; Masuda, Takao; Kannagi, Mari

2006-12-22

Severe acute respiratory syndrome (SARS) is characterized by rapidly progressing respiratory failure resembling acute/adult respiratory distress syndrome (ARDS) associated with uncontrolled inflammatory responses. Here, we demonstrated that, among five accessory proteins of SARS coronavirus (SARS-CoV) tested, 3a/X1 and 7a/X4 were capable of activating nuclear factor kappa B (NF-kappaB) and c-Jun N-terminal kinase (JNK), and significantly enhanced interleukin 8 (IL-8) promoter activity. Furthermore, 3a/X1 and 7a/X4 expression in A549 cells enhanced production of inflammatory chemokines that were known to be up-regulated in SARS-CoV infection. Our results suggest potential involvement of 3a/X1 and 7a/X4 proteins in the pathological inflammatory responses in SARS.

Effects of Relaxing Music on Mental Fatigue Induced by a Continuous Performance Task: Behavioral and ERPs Evidence.

PubMed

Guo, Wei; Ren, Jie; Wang, Biye; Zhu, Qin

2015-01-01

The purpose of this study was to investigate whether listening to relaxing music would help reduce mental fatigue and to maintain performance after a continuous performance task. The experiment involved two fatigue evaluation phases carried out before and after a fatigue inducing phase. A 1-hour AX-continuous performance test was used to induce mental fatigue in the fatigue-inducing phase, and participants' subjective evaluation on the mental fatigue, as well as their neurobehavioral performance in a Go/NoGo task, were measured before and after the fatigue-inducing phase. A total of 36 undergraduate students (18-22 years) participated in the study and were randomly assigned to the music group and control group. The music group performed the fatigue-inducing task while listening to relaxing music, and the control group performed the same task without any music. Our results revealed that after the fatigue-inducing phase, (a) the music group demonstrated significantly less mental fatigue than control group, (b) reaction time significantly increased for the control group but not for the music group, (c) larger Go-P3 and NoGo-P3 amplitudes were observed in the music group, although larger NoGo-N2 amplitudes were detected for both groups. These results combined to suggest that listening to relaxing music alleviated the mental fatigue associated with performing an enduring cognitive-motor task.

Determining the nature of faint X-ray sources from the ASCA Galactic center survey

NASA Astrophysics Data System (ADS)

Lutovinov, A. A.; Revnivtsev, M. G.; Karasev, D. I.; Shimansky, V. V.; Burenin, R. A.; Bikmaev, I. F.; Vorob'ev, V. S.; Tsygankov, S. S.; Pavlinsky, M. N.

2015-05-01

We present the results of the the identification of six objects from the ASCA Galactic center and Galactic plane surveys: AX J173548-3207, AX J173628-3141, AX J1739.5-2910, AX J1740.4-2856, AX J1740.5-2937, and AX J1743.9-2846. Chandra, XMM-Newton, and XRT/Swift X-ray data have been used to improve the positions of the optical counterparts to these sources. Thereafter, we have carried out a series of spectroscopic observations of the established optical counterparts at the RTT-150 telescope. Analysis of X-ray and optical spectra as well as photometric measurements in a wide wavelength range based on optical and infrared catalogs has allowed the nature of the program sources to be determined. Two X-ray objects have been detected in the error circle of AX J173628-3141: one is a coronally active G star and the other may be a symbiotic star, a red giant with an accreting white dwarf. Three sources (AX J1739.5-2910, AX J1740.5-2937, AX J1743.9-2846) have turned out to be active G-K stars, presumably RS CVn objects, one (AX J1740.4-2856) is an M dwarf, and another one (AX J173548-3207) most likely a low-mass X-ray binary in its low state. The distances and corresponding luminosities of the sources in the soft X-ray band (0.5-10 keV) have been estimated; analysis of deep INTEGRAL Galactic center observations has not revealed a statistically significant flux at energies >20 keV from any of them.

γH2AX foci formation in the absence of DNA damage: mitotic H2AX phosphorylation is mediated by the DNA-PKcs/CHK2 pathway.

PubMed

Tu, Wen-Zhi; Li, Bing; Huang, Bo; Wang, Yu; Liu, Xiao-Dan; Guan, Hua; Zhang, Shi-Meng; Tang, Yan; Rang, Wei-Qing; Zhou, Ping-Kun

2013-11-01

Phosphorylated H2AX is considered to be a biomarker for DNA double-strand breaks (DSB), but recent evidence suggests that γH2AX does not always indicate the presence of DSB. Here we demonstrate the bimodal dynamic of H2AX phosphorylation induced by ionizing radiation, with the second peak appearing when G2/M arrest is induced. An increased level of γH2AX occurred in mitotic cells, and this increase was attenuated by DNA-PKcs inactivation or Chk2 depletion, but not by ATM inhibition. The phosphorylation-mimic CHK2-T68D abrogated the attenuation of mitotic γH2AX induced by DNA-PKcs inactivation. Thus, the DNA-PKcs/CHK2 pathway mediates the mitotic phosphorylation of H2AX in the absence of DNA damage. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Human brucellosis mimicking axial spondyloarthritis: a challenge for rheumatologists when applying the 2009 ASAS criteria.

PubMed

Ye, Cong; Shen, Gui-Fen; Li, Shou-Xin; Dong, Ling-Li; Yu, Yi-Kai; Tu, Wei; Zhu, Ying-Zi; Hu, Shao-Xian

2016-06-01

Although the development of the 2009 SpA classification criteria by Assessment of SpondyloArthritis international Society (ASAS) represents an important step towards a better definition of the early disease stage particularly in axial spondyloarthritis (axSpA), the specificity of the criteria has been criticized these days. As the commonest zoonotic infection worldwide, human brucellosis can mimic a large number of diseases, including SpA. This study was performed to determine the frequency of rheumatologic manifestations in patients with brucellosis and the chance of misdiagnosing them as having axSpA in central China. The results showed that clinical manifestations of axSpA could be observed in brucellosis. Over half of patients had back pain, and one fifth of the patients with back pain were less than 45 years old at onset and had the symptom for more than 3 months. Two young males were falsely classified as suffering from axSpA according to the ASAS criteria, and one with MRI proved sacroiliitis was once given Etanercept for treatment. Therefore, differential diagnosis including human brucellosis should always be kept in mind when applying the ASAS criteria, even in traditionally non-endemic areas.

Comparison of Abbott AxSYM and Roche Elecsys 2010 for measurement of BNP and NT-proBNP.

PubMed

Chien, Tzu-I; Chen, Hui-Hou; Kao, Jau-Tsuen

2006-07-15

B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are small cardiac hormones released from the heart. They can be used as an important aid to diagnose congestive heart failure (CHF). We compared the performances of the Abbott AxSYM and Roche Elecsys 2010 for the measurement of BNP and NT-proBNP. The first method uses a microparticle enzyme-linked immunoassay, whereas the other uses chemiluminescent immunometric assay. The CVs using pooled sera ranged from 3.7% to 12.7% for the AxSYM and 0.9% to 2.2% for the Elecsys 2010. The Passing and Bablok regression was Elecsys 2010 NT-proBNP=7.23xAxSYM BNP+2.53. The BNP in EDTA plasma was more stable than in serum. The immunoreactivity difference of NT-proBNP in serum or EDTA plasma was within 10% when stored at 4 degrees Celsius or 25 degrees Celsius for 72 h. Receiver operating characteristic (ROC) curves were different for both assays, and the areas under the curves were 0.704 and 0.841 for the AxSYM and Elecsys 2010 method, respectively. Both assays were not entirely specific for heart failure. The precision and stability for NT-proBNP was better than for BNP in serum. It is important to use method-appropriate reference ranges (or cutoff) for the BNP and NT-proBNP, respectively, in the assessment of CHF.

An optimized posterior axillary boost technique in radiation therapy to supraclavicular and axillary lymph nodes: A comparative study

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

Hernandez, Victor, E-mail: vhernandezmasgrau@gmail.com; Arenas, Meritxell; Müller, Katrin

2013-01-01

To assess the advantages of an optimized posterior axillary (AX) boost technique for the irradiation of supraclavicular (SC) and AX lymph nodes. Five techniques for the treatment of SC and levels I, II, and III AX lymph nodes were evaluated for 10 patients selected at random: a direct anterior field (AP); an anterior to posterior parallel pair (AP-PA); an anterior field with a posterior axillary boost (PAB); an anterior field with an anterior axillary boost (AAB); and an optimized PAB technique (OptPAB). The target coverage, hot spots, irradiated volume, and dose to organs at risk were evaluated and a statisticalmore » analysis comparison was performed. The AP technique delivered insufficient dose to the deeper AX nodes. The AP-PA technique produced larger irradiated volumes and higher mean lung doses than the other techniques. The PAB and AAB techniques originated excessive hot spots in most of the cases. The OptPAB technique produced moderate hot spots while maintaining a similar planning target volume (PTV) coverage, irradiated volume, and dose to organs at risk. This optimized technique combines the advantages of the PAB and AP-PA techniques, with moderate hot spots, sufficient target coverage, and adequate sparing of normal tissues. The presented technique is simple, fast, and easy to implement in routine clinical practice and is superior to the techniques historically used for the treatment of SC and AX lymph nodes.« less

Self-Replicating Quadratics

ERIC Educational Resources Information Center

Withers, Christopher S.; Nadarajah, Saralees

2012-01-01

We show that there are exactly four quadratic polynomials, Q(x) = x [superscript 2] + ax + b, such that (x[superscript 2] + ax + b) (x[superscript 2] - ax + b) = (x[superscript 4] + ax[superscript 2] + b). For n = 1, 2, ..., these quadratic polynomials can be written as the product of N = 2[superscript n] quadratic polynomials in x[superscript…

Preservation of within-compound associations after blocked preexposure to two compound flavors.

PubMed

Espinet, Alfredo; Caramés, José M; Cabo, Fernando

2015-11-01

Three experiments investigated the extinction of the within-compound A↔X association established when two compound flavors, AX and BX, are preexposed in blocks (i.e., AX, AX, AX, ... BX, BX, BX). In Experiment 1, a group of rats received preexposure to a block of AX trials followed by a second block of BX trials (AX-BX), while a second group received blocked preexposure to the same stimuli in the opposite order (BX-AX). Subsequently, flavor A was paired with lithium chloride. This conditioning resulted in a similar reduction of consumption of flavor X in both groups. In Experiment 2 four groups of rats received blocked preexposure to AX-BX, AX-B, A-BX, or A-X. After aversive conditioning of X, consumption of A and B was significantly lower for the groups which received these flavors paired with X than for the groups for which these flavors were presented isolated. In Experiment 3 a group of rats was preexposed to a block of SaltX presentations followed by a block of BX presentations (SaltX-BX), and a second group received blocked preexposure to (BX-SaltX). After subsequent sodium depletion, consumption of X was high and similar for the SaltX-BX and for the BX-SaltX groups. These results indicate that the within-compound association established in the first block of a blocked preexposure is not extinguished when the preexposure phase is concluded. Copyright © 2015 Elsevier B.V. All rights reserved.

The de-epoxidase and epoxidase reactions of Mantoniella squamata (Prasinophyceae) exhibit different substrate-specific reaction kinetics compared to spinach.

PubMed

Frommolt, R; Goss, R; Wilhelm, C

2001-07-01

In vivo the prasinophyceaen alga Mantoniella squamata Manton et Parke uses an incomplete violaxanthin (Vx) cycle, leading to a strong accumulation of antheraxanthin (Ax) under conditions of high light. Here, we show that this zeaxanthin (Zx)-depleted Vx/Ax cycle is caused by an extremely slow second de-epoxidation step from Ax to Zx, and a fast epoxidation from Ax back to Vx in the light. The rate constant of Ax epoxidation is 5 to 6 times higher than the rate constant of Zx formation, implying that Ax is efficiently converted back to Vx before it can be de-epoxidated to Zx. It is, however, only half the rate constant of the first de-epoxidation step from Vx to Ax, thus explaining the observed net accumulation of Ax during periods of strong illumination. When comparing the rate constant of the second de-epoxidation step in M. squamata with Zx formation in spinach (Spinacia oleracea L.) thylakoids, we find a 20-fold reduction in the reaction kinetics of the former. This extremely slow Ax de-epoxidation, which is also exhibited by the isolated Mantoniella violaxanthin de-epoxidase (VDE), is due to a reduced substrate affinity of M. squamata VDE for Ax compared with the VDE of higher plants. Mantoniella VDE, which has a similar Km value for Vx, shows a substantially increased Km for the substrate Ax in comparison with spinach VDE. Our results furthermore explain why Zx formation in Mantoniella cells can only be found at low pH values that represent the pH optimum of VDE. A pH of 5 blocks the epoxidation reaction and, consequently, leads to a slow but appreciable accumulation of Zx.

Evaluating γH2AX in spermatozoa from male infertility patients.

PubMed

Zhong, Hui-zhi; Lv, Fu-tong; Deng, Xue-lian; Hu, Ying; Xie, Dan-ni; Lin, Bin; Mo, Zeng-nan; Lin, Fa-quan

2015-09-01

To investigate whether γH2AX levels were different in the spermatozoa of healthy men compared with infertility patients, and to assess the possible correlations between γH2AX and conventional semen parameters and double-stranded breaks (DSBs) identified with the use of comet assay. Prospective study. Clinical laboratory. Semen from 100 male infertile patients and 100 healthy sperm donors. Human sperm samples were analyzed in terms of World Health Organization parameters. The γH2AX levels were detected by means of flow cytometry. DSBs of sperm were detected by means of comet assay. Morphology slides were made and the sperm morphology assessed according to strict criteria. Conventional semen analyses, γH2AX levels in sperm, DNA DSBs in sperm, and correlations among γH2AX, conventional semen analyses, and DSBs. Concentration, viability, motility, and normal sperm morphology were significantly lower in male infertility patients compared with healthy men. Also, γH2AX levels and the number of DSBs were significantly higher in the sperm of infertile subjects compared with healthy men. γH2AX levels correlated negatively with conventional semen parameters and positively with DSBs. A threshold γH2AX level of 18.55% was identified as a cutoff value to discriminate infertile subjects from fertile control subjects with a specificity of 86.0% and a sensitivity of 83.0%. The positive and negative predictive values of the 18.55% γH2AX threshold were high: 87.7% and 85.5%, respectively. γH2AX levels were higher in the sperm of male infertility patients than in healthy men. γH2AX levels in sperm, as evaluated with the use of flow cytometry, might be a useful biomarker for evaluating DSBs in human spermatozoa. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

γH2AX formation kinetics in PBMCs of rabbits exposed to acute and fractionated radiation and attenuation of focus frequency through preadministration of a combination of podophyllotoxin and rutin hydrate.

PubMed

Yashavarddhan, M H; Shukla, Sandeep K; Srivastava, Nitya N; Suar, Mrutyunjay; Dutta, Sangeeta; Kalita, Bhargab; Ranjan, Rajiv; Singh, Abhinav; Bajaj, Sania; Gupta, Manju L

2016-07-01

DNA damage can be assessed by the quantitation of γH2AX foci that form at DSB sites. This study examines the generation and persistence of γH2AX foci, variability in foci size after acute and fractionated radiation exposure, and the effect of pretreatment with a safe radioprotective formulation termed G-003M on foci generation and persistence. G-003M contains a combination of podophyllotoxin and rutin hydrate, and was administered intramuscularly to rabbits 1 hr prior to Co(60) gamma irradiation. Rabbits were assigned to one of the following treatment groups: untreated, G-003M alone, irradiated (single dose 8 Gy, fractionated 2 Gy/day for 4 days or single dose 2 Gy) or G-003M preadministration followed by radiation exposure. Foci continuously persisted for a week in peripheral blood mononuclear cells of rabbits exposed to a single 8 Gy dose. However, the number of foci gradually decreased after reaching a maximum at 1 h. In rabbits exposed to fractionated radiation, foci detected 1 hr after the final exposure were significantly larger (P < 0.001) than in rabbits exposed to a single 8 Gy dose, but disappeared completely after 24 h. In both groups, foci reappeared on days 11-15 in terminally ill animals. G-003M pretreatment significantly (P < 0.05) attenuated the formation of γH2AX foci in all irradiated rabbits. This study reveals that γH2AX focus assessment could be used to confirm radiation exposure, that focus size reflects the type of radiation exposure (acute or fractionated), that the re-appearance of foci is a strong indicator of imminent death in animals, and that G-003M provides protection against radiation. Environ. Mol. Mutagen. 57:455-468, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A comparison of two types of velocity models for the lunar crust: Smooth continuous and stepwise layered

NASA Technical Reports Server (NTRS)

Gangi, A. F.

1978-01-01

The data from the Apollo-14 and Apollo-16 Active Seismic Experiments were reanalyzed and show that a power-law velocity variation with depth is consistent with both the traveltimes and amplitudes of the first arrivals for source-to-geophone separations up to 32m. The data were improved by removing spurious glithches, flickering and stacking. While this improved the signal-to-noise ratios, it was not possible to measure the arrivals beyond 32m. The physical evidence that the shallow lunar regolith is made up of fine particles adds weight to the 1/6-power velocity model. The 1/6-power law predicts the traveltime t(x), varies with separation, x, as t(x) = t sub 0 (x/x sub 0) to the 5/6 power and, using a first-order theory, the amplitude, A(x), varies as A(x) = A sub 0 (x/x sub 0) to the (13-m)/12, M 1; the layer-velocity model predicts t(x) = t sub 0 (x/xsub 0) and A(x) = A sub 0 (x/x sub 0) to the 2nd power.

Performance characteristics of the ARCHITECT Active-B12 (Holotranscobalamin) assay.

PubMed

Merrigan, Stephen D; Owen, William E; Straseski, Joely A

2015-01-01

Vitamin B12 (cobalamin) is a necessary cofactor in methionine and succinyl-CoA metabolism. Studies estimate the deficiency prevalence as high as 30% in the elderly population. Ten to thirty percent of circulating cobalamin is bound to transcobalamin (holotranscobalamin, holoTC) which can readily enter cells and is therefore considered the bioactive form. The objective of our study was to evaluate the analytical performance of a high-throughput, automated holoTC assay (ARCHITECT i2000(SR) Active-B12 (Holotranscobalamin)) and compare it to other available methods. Manufacturer-specified limits of blank (LoB), detection (LoD), and quantitation (LoQ), imprecision, interference, and linearity were evaluated for the ARCHITECT HoloTC assay. Residual de-identified serum samples were used to compare the ARCHITECT HoloTC assay with the automated AxSYM Active-B12 (Holotranscobalamin) assay (Abbott Diagnostics) and the manual Active-B12 (Holotranscobalamin) Enzyme Immunoassay (EIA) (Axis-Shield Diagnostics, Dundee, Scotland, UK). Manufacturer's claims of LoB, LoD, LoQ, imprecision, interference, and linearity to the highest point tested (113.4 pmol/L) were verified for the ARCHITECT HoloTC assay. Method comparison of the ARCHITECT HoloTC to the AxSYM HoloTC produced the following Deming regression statistics: (ARCHITECT(HoloTc)) = 0.941 (AxSYM(HoloTC)) + 1.2 pmol/L, S(y/x) = 6.4, r = 0.947 (n = 98). Comparison to the Active-B12 EIA produced: (ARCHITECT(HoloTC)) = 1.105 (EIA(Active-B12)) - 6.8 pmol/L, S(y/x) = 11.0, r = 0.950 (n = 221). This assay performed acceptably for LoB, LoD, LoQ, imprecision, interference, linearity and method comparison to the predicate device (AxSYM). An additional comparison to a manual Active-B12 EIA method performed similarly, with minor exceptions. This study determined that the ARCHITECT HoloTC assay is suitable for routine clinical use, which provides a high-throughput alternative for automated testing of this emerging marker of cobalamin deficiency.

A case of Weill-Marchesani syndrome with inversion of chromosome 15.

PubMed

Chung, Jae Lim; Kim, Sun Woong; Kim, Ji Hyun; Kim, Tae-Im; Lee, Hyung Keun; Kim, Eung Kweon

2007-12-01

To present a case of Weill-Marchesani syndrome with corneal endothelial dysfunction due to anterior dislocation of a spherophakic lens and corneolenticular contact. A 17-year-old woman presented with high myopia and progressive visual disturbance. She was of short stature and had brachydactyly. Her initial Snellen best corrected visual acuity (BCVA) was 20/50 (-sph 20.50 -cyl 3.00 Ax 180) in her right eye and 20/40 (-sph 16.00 -cyl 6.00 Ax 30) in her left eye. Slit lamp examination revealed a dislocated spherophakic lens touching corenal endothelium. A microspherophakic lens, hypoplastic ciliary body, and elongated zonules were confirmed on rotating Scheimpflug camera (Pentacam) and on ultrasound biomicroscopy. Specular microscopy showed corneal endothealial dysfunction. Systemic evaluation was performed, and chromosomal study showed 46, XX, inv (15) (q13qter). The patient was diagnosed with Weill-Marchesani syndrome. Due to impending corneal decompensation, phacoemulsification and suture fixation of the intraocular lens were performed. The operation and postoperative course were uneventful. Three months postoperatively, the visual acuity was 20/30 (OD) and 20/40 (OS) without correction, and BCVA was 20/20 (+sph 0.50 -cyl 2.00 Ax 160 : OD) and 20/25 (+sph 1.50 -cyl 3.00 Ax 30 : OS). During the follow-up period, increased corneal endothelial counts, hexagonality, and decreased corneal thickness were achieved. In Weill-Marchesani syndrome with a chromosomal anomaly, a dislocated spherophakic lens may cause severe corneal endothelial dysfunction due to corneolenticular contact, and prompt lensectomy is important to prevent such complications.

Amoxicillin haptenates intracellular proteins that can be transported in exosomes to target cells.

PubMed

Sánchez-Gómez, F J; González-Morena, J M; Vida, Y; Pérez-Inestrosa, E; Blanca, M; Torres, M J; Pérez-Sala, D

2017-03-01

Allergic reactions to β-lactams are among the most frequent causes of drug allergy and constitute an important clinical problem. Drug covalent binding to endogenous proteins (haptenation) is thought to be required for activation of the immune system. Nevertheless, neither the nature nor the role of the drug protein targets involved in this process is fully understood. Here, we aim to identify novel intracellular targets for haptenation by amoxicillin (AX) and their cellular fate. We have treated B lymphocytes with either AX or a biotinylated analog (AX-B). The identification of protein targets for haptenation by AX has been approached by mass spectrometry and immunoaffinity techniques. In addition, intercellular communication mediated by the delivery of vesicles loaded with AX-B-protein adducts has been explored by microscopy techniques. We have observed a complex pattern of AX-haptenated proteins. Several novel targets for haptenation by AX in B lymphocytes have been identified. AX-haptenated proteins were detected in cell lysates and extracellularly, either as soluble proteins or in lymphocyte-derived extracellular vesicles. Interestingly, exosomes from AX-B-treated cells showed a positive biotin signal in electron microscopy. Moreover, they were internalized by endothelial cells, thus supporting their involvement in intercellular transfer of haptenated proteins. These results represent the first identification of AX-mediated haptenation of intracellular proteins. Moreover, they show that exosomes can constitute a novel vehicle for haptenated proteins, and raise the hypothesis that they could provide antigens for activation of the immune system during the allergic response. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Residual γH2AX foci after ex vivo irradiation of patient samples with known tumour-type specific differences in radio-responsiveness.

PubMed

Menegakis, Apostolos; De Colle, Chiara; Yaromina, Ala; Hennenlotter, Joerg; Stenzl, Arnulf; Scharpf, Marcus; Fend, Falko; Noell, Susan; Tatagiba, Marcos; Brucker, Sara; Wallwiener, Diethelm; Boeke, Simon; Ricardi, Umberto; Baumann, Michael; Zips, Daniel

2015-09-01

To apply our previously published residual ex vivo γH2AX foci method to patient-derived tumour specimens covering a spectrum of tumour-types with known differences in radiation response. In addition, the data were used to simulate different experimental scenarios to simplify the method. Evaluation of residual γH2AX foci in well-oxygenated tumour areas of ex vivo irradiated patient-derived tumour specimens with graded single doses was performed. Immediately after surgical resection, the samples were cultivated for 24h in culture medium prior to irradiation and fixed 24h post-irradiation for γH2AX foci evaluation. Specimens from a total of 25 patients (including 7 previously published) with 10 different tumour types were included. Linear dose response of residual γH2AX foci was observed in all specimens with highly variable slopes among different tumour types ranging from 0.69 (95% CI: 1.14-0.24) to 3.26 (95% CI: 4.13-2.62) for chondrosarcomas (radioresistant) and classical seminomas (radiosensitive) respectively. Simulations suggest that omitting dose levels might simplify the assay without compromising robustness. Here we confirm clinical feasibility of the assay. The slopes of the residual foci number are well in line with the expected differences in radio-responsiveness of different tumour types implying that intrinsic radiation sensitivity contributes to tumour radiation response. Thus, this assay has a promising potential for individualized radiation therapy and prospective validation is warranted. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

On improving linear solver performance: a block variant of GMRES

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

Baker, A H; Dennis, J M; Jessup, E R

2004-05-10

The increasing gap between processor performance and memory access time warrants the re-examination of data movement in iterative linear solver algorithms. For this reason, we explore and establish the feasibility of modifying a standard iterative linear solver algorithm in a manner that reduces the movement of data through memory. In particular, we present an alternative to the restarted GMRES algorithm for solving a single right-hand side linear system Ax = b based on solving the block linear system AX = B. Algorithm performance, i.e. time to solution, is improved by using the matrix A in operations on groups of vectors.more » Experimental results demonstrate the importance of implementation choices on data movement as well as the effectiveness of the new method on a variety of problems from different application areas.« less

Event Structure and Cognitive Control

ERIC Educational Resources Information Center

Reimer, Jason F.; Radvansky, Gabriel A.; Lorsbach, Thomas C.; Armendarez, Joseph J.

2015-01-01

Recently, a great deal of research has demonstrated that although everyday experience is continuous in nature, it is parsed into separate events. The aim of the present study was to examine whether event structure can influence the effectiveness of cognitive control. Across 5 experiments we varied the structure of events within the AX-CPT by…

40 CFR 51.1101 - Applicability of part 51.

Code of Federal Regulations, 2014 CFR

2014-07-01

... provisions in subparts A-X of part 51 apply to areas for purposes of the 2008 NAAQS to the extent they are... 40 Protection of Environment 2 2014-07-01 2014-07-01 false Applicability of part 51. 51.1101 Section 51.1101 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS...

40 CFR 51.1101 - Applicability of part 51.

Code of Federal Regulations, 2013 CFR

2013-07-01

... provisions in subparts A-X of part 51 apply to areas for purposes of the 2008 NAAQS to the extent they are... 40 Protection of Environment 2 2013-07-01 2013-07-01 false Applicability of part 51. 51.1101 Section 51.1101 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS...

40 CFR 51.1101 - Applicability of part 51.

Code of Federal Regulations, 2012 CFR

2012-07-01

... provisions in subparts A-X of part 51 apply to areas for purposes of the 2008 NAAQS to the extent they are... 40 Protection of Environment 2 2012-07-01 2012-07-01 false Applicability of part 51. 51.1101 Section 51.1101 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS...

Efficacy and safety of biological and targeted-synthetic DMARDs: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis

PubMed Central

Regel, Andrea; van der Heijde, Désirée; Braun, Jürgen; Baraliakos, Xenofon; Landewé, Robert; Van den Bosch, Filip; Falzon, Louise; Ramiro, Sofia

2017-01-01

Objectives To update the evidence for the efficacy and safety of (b)biological and (ts)targeted-synthetic disease-modifying anti-rheumatic drugs (DMARDs) in patients with axial spondyloarthritis (axSpA) to inform the 2016 update of the Assessment of SpondyloArthritis international Society/European League Against Rheumatism (ASAS/EULAR) recommendations for the management of axSpA. Methods Systematic literature review (2009–2016) for randomised controlled trials (RCT), including long-term extensions, strategy trials and observational studies (the latter was only for safety assessment and a comparator was required). Interventions were any bDMARD or tsDMARD. All relevant efficacy and safety outcomes were included. Results 76 papers and 24 abstracts fulfilled the inclusion criteria. Large treatment effects were found both in radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA) for all tumour necrosis factor inhibitors (TNFi) (NNT to achieve ASAS40 response ranged between 2.6–5.2 for r-axSpA and 2.3–5.4 for nr-axSpA). For nr-axSpA, efficacy was superior for those who had objective signs of inflammation (positive C reactive protein or inflammation on MRI-SI). Secukinumab 150 mg has shown efficacy in two phase 3 RCTs (NNT to achieve ASAS40 response: 3.4 and 4.0). Ustekinumab and tofacitinib have shown positive results in phase 2/proof-of-concept trials; trials with apremilast, rituximab, interleukin (IL)-6 antagonists and abatacept have failed their primary end points. New (unknown) safety signals were not found in the trials but long-term observational safety data for TNFi are still scarce. Conclusions New evidence supports the efficacy and safety of TNFi both in r-axSpA and nr-axSpA. Secukinumab is the first drug targeting the IL-17 pathway in r-axSpA that has shown efficacy. PMID:28176964

Analysis of HLA-B15 and HLA-B27 in spondyloarthritis with peripheral and axial clinical patterns

PubMed Central

Londono, John; Santos, Ana Maria; Peña, Paola; Calvo, Enrique; Espinosa, Luis R; Reveille, John D; Vargas-Alarcon, Gilberto; Jaramillo, Carlos A; Valle-Oñate, Rafael; Avila, Mabel; Romero, Consuelo; Medina, Juan F

2015-01-01

Objective Human leucocyte antigen (HLA) B27 and HLA-B15 are associated with spondyloarthritis (SpA). Recent Assessment of SpondyloArthritis international Society (ASAS) criteria emphasise a distinction between SpA with axial and peripheral patterns. We analysed whether HLA-A, HLA-B and HLA-DRB1 alleles could associate with these patterns. Methods We studied 100 healthy individuals and 178 patients with SpA according to European Spondyloarthropathy Study Group (ESSG) criteria. Patients were then classified according to ASAS criteria, the axial spondyloarthritis pattern (axSpA) being defined by ascertained sacroiliitis and the peripheral pattern (pSpA) by enthesitis and/or arthritis in extremities. A combined ax/p pattern was also considered. Results Only HLA-B27 and HLA-B15 alleles were associated with SpA. ASAS criteria for axSpA were met in 152 patients (12 with isolated axSpA and 140 with a combined ax/p patterns). When the ASAS peripheral criteria were applied, 161 patients met these criteria (13 with isolated pSpA and 148 with a combined ax/p pattern). HLA-B27 was found in 83% of patients with axSpA and 43% of ax/pSpA patients according to axASAS. HLA-B27 occurred in 7% controls but not in any patient with isolated pSpA. HLA-B15 was encountered in 31% of patients with isolated pSpA and 20% of ax/pSpA patients according to pASAS criteria. Moreover, 2 healthy controls, but none of our patients with isolated axSpA were positive for HLA-B15. Conclusions Our data suggest that the presence of HLA-B15 favours the development of isolated/combined peripheral rather than isolated axSpA, while HLA-B27 promotes an isolated/combined axial disease and excludes a peripheral pattern. HLA-B15 should be considered in addition to HLA-B27 when diagnosing patients with SpA according to ASAS criteria. PMID:26560062

γ-H2AX formation in response to interstrand crosslinks requires XPF in human cells

PubMed Central

Mogi, Seiki; Oh, Dennis H.

2009-01-01

To further define the molecular mechanisms involved in processing interstrand crosslinks, we monitored the formation of phosphorylated histone H2AX (γ-H2AX), which is generated in chromatin near double strand break sites, following DNA damage in normal and repair-deficient human cells. Following treatment with a psoralen derivative and ultraviolet A radiation doses that produce significant numbers of crosslinks, γ-H2AX levels in nucleotide excision repair-deficient XP-A fibroblasts (XP12RO-SV) increased to levels that were twice those observed in normal control GM637 fibroblasts. A partial XPA revertant cell line (XP129) that is proficient in crosslink removal, exhibited reduced γ-H2AX levels that were intermediate between those of GM637 and XP-A cells. XP-F fibroblasts (XP2YO-SV and XP3YO) that are also repair-deficient exhibited γ-H2AX levels below even control fibroblasts following treatment with psoralen and ultraviolet A radiation. Similarly, another crosslinking agent, mitomycin C, did not induce γ-H2AX in XP-F cells, although it did induce equivalent levels of γ-H2AX in XPA and control GM637 cells. Ectopic expression of XPF in XP-F fibroblasts restored γ-H2AX induction following treatment with crosslinking agents. Angelicin, a furocoumarin which forms only monoadducts and not crosslinks following ultraviolet A radiation, as well as ultraviolet C radiation, resulted only in weak induction of γ-H2AX in all cells, suggesting that the double strand breaks observed with psoralen and ultraviolet A treatment result preferentially following crosslink formation. These results indicate that XPF is required to form γ-H2AX and likely double strand breaks in response to interstrand crosslinks in human cells. Furthermore, XPA may be important to allow psoralen interstrand crosslinks to be processed without forming a double strand break intermediate. PMID:16678501

Study on γH2AX Expression of Lymphocytes as a Biomarker In Radiation Biodosimetry

PubMed Central

Pan, Yan; Gao, Gang; Ruan, Jian Lei; Liu, Jian Xiang

2016-01-01

Flow cytometry analysis was used to detect the changes of γH2AX protein expression in human peripheral blood lymphocytes. In the dose-effect study, the expression of γH2AX was detected 1 h after irradiation with 60Co γ-rays at doses of 0, 0.5, 1, 2, 4, and 6 Gy. Blood was cultivated for 0, 1, 2, 4, 6, 12, and 24 h after 4 Gy 60Co γ-rays irradiation for the time-effect study. At the same time, the blood was divided into four treatment groups (ultraviolet [UV] irradiation, 60Co γ-rays irradiation, UV plus 60Co γ-rays irradiation, and control group) to detect the changes of protein expression of γH2AX. The results showed that the γH2AX protein expression was in dose-effect and time-effect relationship with 60Co γ-rays. The peak expression of γH2AX was at 1 h after 60Co γ-ray irradiation and began to decrease quickly. Compared to irradiation with 60Co γ-rays alone, the expression of γH2AX was not significantly changed after irradiation with 60Co γ-rays plus UV. Dose rate did not significantly change the expression of γH2AX. The expression of γH2AX induced by 60Co γ-rays was basically consistent with the mice in vivo and in vitro. The results revealed that the detection of γH2AX protein expression changes in peripheral blood lymphocyte by flow cytometry analysis is reasonable and may be useful for biodosimetry. PMID:28217286

Assessing the attractive/repulsive force balance in axial cyclohexane C-Hax ···Yax contacts: A combined computational analysis in monosubstituted cyclohexanes.

PubMed

Silva Lopez, Carlos; Nieto Faza, Olalla; De Proft, Frank; Kolocouris, Antonios

2016-11-15

The interactions of axial substituents in monosubstituted cyclohexane rings are studied in this work using an array of different computational techniques. Additionally, the anomalous axial preference for some bulky substituents is related to stabilizing dispersion interactions. We find that the C-H ax ···Y ax contacts for various substituents with distances ranging from 2 to ∼5 Å may include attractive dispersion forces that can affect the conformational equilibrium; these forces co-exist with Pauli repulsive forces effected by Y ax group due to van der Waals sphere penetration. At distances between 2 and 3 Å stabilizing electron transfer interactions were calculated and the combination of natural bond orbital and QTAIM analysis showed that, in certain cases, Y ax  =  t Bu, C ax -O or C ax  = O or S ax  = O or C ax  = S this interaction can be characterized as an improper H-bond. DFT-D3 and non-covalent interactions calculations (NCIs) in cyclohexane derivatives with Y ax  = SiOR 3 including H Yax ···H cy surfaces at distances ranging between 4 and 6 Å suggest that dispersion has a clear effect on the experimentally observed stabilization of the axial conformer. NCIs computed from the reduced density gradient help to visually identify and analyze these interactions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Water-extractable and water-unextractable arabinoxylans affect gluten agglomeration behavior during wheat flour gluten-starch separation.

PubMed

Frederix, Sofie A; Van Hoeymissen, Klaartje E; Courtin, Christophe M; Delcour, Jan A

2004-12-29

Water-extractable arabinoxylan (WE-AX) of variable molecular weight (MW) and water-unextractable arabinoxylan (WU-AX) were added to wheat flour to study their effect on gluten agglomeration in a dough and batter gluten-starch separation process with recovery of gluten from the batter with a set of vibrating sieves (400, 250, and 125 microm). Low MW WE-AX had almost no impact on the distribution of the gluten on the different sieves. High MW WE-AX decreased yields of the largest (400 microm sieve) gluten aggregates, more than their medium MW counterparts, indicating the importance of AX MW for their effect on gluten interactions. Correlations between the total level of gluten protein recovered on the three sieves and the batter extract viscosity as well as between the proportion of gluten protein recovered on the 400 microm sieve to that on the three sieves and the batter extract viscosity pointed to the importance of viscosity as an indicator for gluten agglomeration, as did the fact that another viscosity increasing plant polysaccharide (guar gum) also negatively influenced gluten agglomeration. However, the obtained data cannot rule out that AX and guar gum also exert steric effects on gluten agglomeration. WU-AX, present as discrete cell wall fragments, had a negative impact on the level of large gluten aggregates. Taken together, the results show that both native WE-AX and WU-AX detrimentally impact gluten agglomeration.

Uniqueness of boundary blow-up solutions on exterior domain of RN

NASA Astrophysics Data System (ADS)

Dong, Wei; Pang, Changci

2007-06-01

In this paper, we consider the existence and uniqueness of positive solutions of the degenerate logistic type elliptic equation where N[greater-or-equal, slanted]2, D[subset of]RN is a bounded domain with smooth boundary and a(x), b(x) are continuous functions on RN with b(x)[greater-or-equal, slanted]0, b(x)[not identical with]0. We show that under rather general conditions on a(x) and b(x) for large x, there exists a unique positive solution. Our results improve the corresponding ones in [W. Dong, Y. Du, Unbounded principal eigenfunctions and the logistic equation on RN, Bull. Austral. Math. Soc. 67 (2003) 413-427] and [Y. Du, L. Ma, Logistic type equations on RN by a squeezing method involving boundary blow-up solutions, J. London Math. Soc. (2) 64 (2001) 107-124].

The histone variant H2A.X is a regulator of the epithelial-mesenchymal transition.

PubMed

Weyemi, Urbain; Redon, Christophe E; Choudhuri, Rohini; Aziz, Towqir; Maeda, Daisuke; Boufraqech, Myriem; Parekh, Palak R; Sethi, Taresh K; Kasoji, Manjula; Abrams, Natalie; Merchant, Anand; Rajapakse, Vinodh N; Bonner, William M

2016-02-15

The epithelial-mesenchymal transition (EMT), considered essential for metastatic cancer, has been a focus of much research, but important questions remain. Here, we show that silencing or removing H2A.X, a histone H2A variant involved in cellular DNA repair and robust growth, induces mesenchymal-like characteristics including activation of EMT transcription factors, Slug and ZEB1, in HCT116 human colon cancer cells. Ectopic H2A.X re-expression partially reverses these changes, as does silencing Slug and ZEB1. In an experimental metastasis model, the HCT116 parental and H2A.X-null cells exhibit a similar metastatic behaviour, but the cells with re-expressed H2A.X are substantially more metastatic. We surmise that H2A.X re-expression leads to partial EMT reversal and increases robustness in the HCT116 cells, permitting them to both form tumours and to metastasize. In a human adenocarcinoma panel, H2A.X levels correlate inversely with Slug and ZEB1 levels. Together, these results point to H2A.X as a regulator of EMT.

Behavior of Triticum durum Desf. arabinoxylans and arabinogalactan peptides during industrial pasta processing.

PubMed

Ingelbrecht, J A; Verwimp, T; Grobet, P J; Delcour, J A

2001-04-01

Three industrial pasta processing lines for different products (macaroni, capellini and instant noodles) were sampled at three subsequent stages (semolina, extruded, and dried end products) in the process. Arabinoxylans (AX) and arabinogalactan peptides (AGP) were analyzed. Although very low endoxylanase activities were measured, the level of water-extractable AX (WE-AX) increased, probably because of mechanical forces. No change was observed in the level and structural characteristics of AGP. The WE-AX molecular weight (MW) profiles showed a very small shift toward lower MW profiles; those of AGP revealed no changes as a result of the production process. After separation of WE-AX and AGP, (1)H NMR analysis and gas chromatography of the alditol acetates obtained following hydrolysis, reduction, and acetylation revealed no changes in the arabinose substitution profile of the WE-AX samples during pasta processing. At optimal cooking times, WE-AX losses in the cooking water are small (maximally 5.9%). However, the loss of AGP is more pronounced (maximally 25.0%). Overcooking led to more losses of both components.

TERT, HRAS, and EIF1AX Mutations in a Patient with Follicular Adenoma.

PubMed

Topf, Michael C; Wang, Zi-Xuan; Tuluc, Madalina; Pribitkin, Edmund A

2018-06-01

Molecular markers are increasingly used as diagnostic tools in the management of thyroid nodules. There is a paucity of studies evaluating the prevalence of molecular markers in benign lesions. A 68-year-old woman with hypothyroidism presented with a right thyroid nodule, which was atypia of undetermined significance on cytology. The fine-needle aspirate of the nodule was examined with next-generation sequencing and found to harbor a C228T mutation in the TERT gene, a Q61R mutation in the HRAS gene, and an A113_splice mutation in the EIF1AX gene. Right thyroid lobectomy was performed, with final pathology showing follicular adenoma. All three mutations detected in the original fine-needle aspirate specimen were detected in the final surgical specimen as well. A rare case of TERT, HRAS, and EIF1AX mutations is reported in a patient with follicular adenoma. TERT promoter mutations may be an early genetic event in the molecular pathogenesis of follicular thyroid carcinoma.

Comparison of the induction and disappearance of DNA double strand breaks and gamma-H2AX foci after irradiation of chromosomes in G1-phase or in condensed metaphase cells.

PubMed

Kato, Takamitsu A; Okayasu, Ryuichi; Bedford, Joel S

2008-03-01

The induction and disappearance of DNA double strand breaks (DSBs) after irradiation of G1 and mitotic cells were compared with the gamma-H2AX foci assay and a gel electrophoresis assay. This is to determine whether cell cycle related changes in chromatin structure might influence the gamma-H2AX assay which depends on extensive phosphorylation and dephosphorylation of the H2AX histone variant surrounding DSBs. The disappearance of gamma-H2AX foci after irradiation was much slower for mitotic than for G1 cells. On the other hand, no difference was seen for the gel electrophoresis assay. Our data may suggest the limited accessibility of dephosphorylation enzyme in irradiated metaphase cells or trapped gamma-H2AX in condensed chromatin.

Limited radiographic progression and sustained reductions in MRI inflammation in patients with axial spondyloarthritis: 4-year imaging outcomes from the RAPID-axSpA phase III randomised trial.

PubMed

van der Heijde, Désirée; Baraliakos, Xenofon; Hermann, Kay-Geert A; Landewé, Robert B M; Machado, Pedro M; Maksymowych, Walter P; Davies, Owen R; de Peyrecave, Natasha; Hoepken, Bengt; Bauer, Lars; Nurminen, Tommi; Braun, Juergen

2018-05-01

To report 4-year imaging outcomes in the RAPID-axSpA (NCT01087762) study of patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA), treated with certolizumab pegol (CZP). This phase III, randomised trial was placebo-controlled and double-blind to week 24, dose-blind to week 48 and open-label to week 204. Patients fulfilling the Assessment of Spondyloarthritis International Society (ASAS) axSpA criteria with active disease were stratified (AS/nr-axSpA) according to the modified New York (mNY) criteria at randomisation. Spinal radiographs were assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). MRI inflammation used the Spondyloarthritis Research Consortium of Canada (SPARCC) score for sacroiliac joints (SIJ) and the Berlin spinal score (remission defined as SPARCC <2 and Berlin ≤2, respectively). MRI improvements from baseline (BL) to week 12 were maintained to week 204 (SPARCC BL: AS=8.5, nr-axSpA=7.5; SPARCC week 204: AS=1.3, nr-axSpA=2.4; Berlin BL: AS=7.4, nr-axSpA=4.4; Berlin week 204: AS=2.6, nr-axSpA=1.9). 66.7% of patients with AS and 69.6% of patients with nr-axSpA with BL SPARCC scores ≥2, and 65.4% of patients with AS and 57.3% of patients with nr-axSpA with BL Berlin score >2, achieved remission at week 204. Mean mSASSS change in AS from BL to week 204 was 0.98 (95% CI 0.34, 1.63); 0.67 (95% CI 0.21,1.13) from BL to week 96; and 0.31 (95% CI 0.02,0.60) from week 96 to week 204. Corresponding nr-axSpA changes were 0.06 (95% CI -0.17,0.28), -0.01 (95% CI -0.19,0.17) and 0.07 (95% CI -0.07,0.20). 4.5% of patients with nr-axSpA fulfilled the mNY criteria at week 204, while 4.3% of patients with AS no longer did so. In patients with CZP-treated axSpA, rapid decreases in spinal and SIJ MRI inflammation were maintained to week 204. Overall, 4-year spinal progression was low, with less progression during years 2-4 than 0-2. Radiographic SIJ grading changes demonstrated limited progression. NCT01087762; Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Optimizing the identification of patients with axial spondyloarthritis in primary care--the case for a two-step strategy combining the most relevant clinical items with HLA B27.

PubMed

Braun, Annalina; Gnann, Holger; Saracbasi, Ertan; Grifka, Joachim; Kiltz, Uta; Letschert, Katrin; Braun, Jürgen

2013-08-01

The combination of clinical items suggestive of inflammatory back pain has proved useful for early identification of patients with axial SpA (axSpA) in primary care. However, whether HLA B27 contributes to that is unclear, and published recommendations have advised against it. In this study, we reanalysed data of that trial in relation to the HLA B27 results. Consecutive patients <45 years old (n = 950) with back pain (BP) >2 months presenting to 143 orthopaedists were referred to 36 rheumatologists who made the diagnosis. The predictive value of HLA B27 (n = 298) alone and in combination, including modelling and a two-step strategy, was calculated. Among all patients (mean age 36 years, 52% female, median duration of BP 32 months), 107 had axSpA (36%). Using a simple model, HLA B27 alone performed better than all combinations of clinical items and adding it did not improve likelihood ratios (LRs). Using modelling, two-phase strategies were analysed. Additional items were only relevant in the HLA B27-negative group: improvement by movement, buttock pain and psoriasis. Combining this information revealed the presumably best strategy to predict axSpA in primary care: more than one of these items or HLA B27 need to be present (sensitivity 80.4%, specificity 75.4%, LR+ 3.27 and LR- 0.26). This is the first study to show that patients with axSpA are more reliably identified in primary care by a strategy that includes HLA B27. Because of the two-step approach, the test needs to be performed in only about half of patients with chronic BP.

Adaptation of Chinese and English versions of the Ankylosing Spondylitis quality of life (ASQoL) scale for use in Singapore.

PubMed

Leung, Ying Ying; Lee, Weixian; Lui, Nai Lee; Rouse, Matthew; McKenna, Stephen P; Thumboo, Julian

2017-08-17

To cross-culturally adapt and validate the Singapore Chinese and Singapore English versions of the Ankylosing Spondylitis Quality of Life (ASQoL) scales. Translation of the ASQoL into Singapore Chinese and English was performed by professional and lay translation panels. Field-testing for face and content validity was performed by interviewing ten Chinese speaking and ten English speaking axial spondyloarthritis (AxSpA) patients. AxSpA patients (either Chinese or English speaking) were invited to take part in validation surveys. The Health Assessment Questionnaire (HAQ), Short Form Health Survey (SF-36), Bath Indices, and other measures of disease activity were used as comparator scales for convergent validity. A separate sample of AxSpA patients were invited to participate in a test-retest postal study, with 2 weeks between administrations. The cross-sectional study included 183 patients (77% males, 82% English speaking), with a mean (SD) age of 39.4 (13.7) years. The ASQoL had excellent internal consistency (Cronbach's alpha = 0.88), and correlated moderately with all the comparator scales. The ASQoL was able to distinguish between patients grouped by disease activity and perceived general health. The ASQoL fulfilled the Rasch model analysis for fit, reliability and unidimensionality requirements. No significant differential item functioning was noted for gender, age below or above 50 years, and language of administration. Test-retest reliability was good (r = 0.81). The ASQoL was adapted into Singapore Chinese and English language versions, and shown to be culturally relevant, valid and reliable when used with combined samples of AxSpA patients who speak either Chinese or English.

AX+/BX- Discrimination Learning in the Fear-Potentiated Startle Paradigm in Monkeys

ERIC Educational Resources Information Center

Winslow, James T.; Noble, Pamela L.; Davis, Michael

2008-01-01

Individuals with anxiety disorders often do not respond to safety signals and hence continue to be afraid and anxious. Consequently, it is important to develop paradigms in animals that can directly study brain systems involved in learning about, and responding to, safety signals. We previously developed a discrimination procedure in rats of the…

Risk Factor Detection as a Metric of STARHS Performance for HIV Incidence Surveillance Among Female Sex Workers in Kigali, Rwanda

PubMed Central

Braunstein, Sarah L; van de Wijgert, Janneke H; Vyankandondera, Joseph; Kestelyn, Evelyne; Ntirushwa, Justin; Nash, Denis

2012-01-01

Background: The epidemiologic utility of STARHS hinges not only on producing accurate estimates of HIV incidence, but also on identifying risk factors for recent HIV infection. Methods: As part of an HIV seroincidence study, 800 Rwandan female sex workers (FSW) were HIV tested, with those testing positive further tested by BED-CEIA (BED) and AxSYM Avidity Index (Ax-AI) assays. A sample of HIV-negative (N=397) FSW were followed prospectively for HIV seroconversion. We compared estimates of risk factors for: 1) prevalent HIV infection; 2) recently acquired HIV infection (RI) based on three different STARHS classifications (BED alone, Ax-AI alone, BED/Ax-AI combined); and 3) prospectively observed seroconversion. Results: There was mixed agreement in risk factors between methods. HSV-2 coinfection and recent STI treatment were associated with both prevalent HIV infection and all three measures of recent infection. A number of risk factors were associated only with prevalent infection, including widowhood, history of forced sex, regular alcohol consumption, prior imprisonment, and current breastfeeding. Number of sex partners in the last 3 months was associated with recent infection based on BED/Ax-AI combined, but not other STARHS-based recent infection outcomes or prevalent infection. Risk factor estimates for prospectively observed seroconversion differed in magnitude and direction from those for recent infection via STARHS. Conclusions: Differences in risk factor estimates by each method could reflect true differences in risk factors between the prevalent, recently, or newly infected populations, the effect of study interventions (among those followed prospectively), or assay misclassification. Similar investigations in other populations/settings are needed to further establish the epidemiologic utility of STARHS for identifying risk factors, in addition to incidence rate estimation. PMID:23056162

Analysis of HLA-B15 and HLA-B27 in spondyloarthritis with peripheral and axial clinical patterns.

PubMed

Londono, John; Santos, Ana Maria; Peña, Paola; Calvo, Enrique; Espinosa, Luis R; Reveille, John D; Vargas-Alarcon, Gilberto; Jaramillo, Carlos A; Valle-Oñate, Rafael; Avila, Mabel; Romero, Consuelo; Medina, Juan F

2015-11-11

Human leucocyte antigen (HLA) B27 and HLA-B15 are associated with spondyloarthritis (SpA). Recent Assessment of SpondyloArthritis international Society (ASAS) criteria emphasise a distinction between SpA with axial and peripheral patterns. We analysed whether HLA-A, HLA-B and HLA-DRB1 alleles could associate with these patterns. We studied 100 healthy individuals and 178 patients with SpA according to European Spondyloarthropathy Study Group (ESSG) criteria. Patients were then classified according to ASAS criteria, the axial spondyloarthritis pattern (axSpA) being defined by ascertained sacroiliitis and the peripheral pattern (pSpA) by enthesitis and/or arthritis in extremities. A combined ax/p pattern was also considered. Only HLA-B27 and HLA-B15 alleles were associated with SpA. ASAS criteria for axSpA were met in 152 patients (12 with isolated axSpA and 140 with a combined ax/p patterns). When the ASAS peripheral criteria were applied, 161 patients met these criteria (13 with isolated pSpA and 148 with a combined ax/p pattern). HLA-B27 was found in 83% of patients with axSpA and 43% of ax/pSpA patients according to axASAS. HLA-B27 occurred in 7% controls but not in any patient with isolated pSpA. HLA-B15 was encountered in 31% of patients with isolated pSpA and 20% of ax/pSpA patients according to pASAS criteria. Moreover, 2 healthy controls, but none of our patients with isolated axSpA were positive for HLA-B15. Our data suggest that the presence of HLA-B15 favours the development of isolated/combined peripheral rather than isolated axSpA, while HLA-B27 promotes an isolated/combined axial disease and excludes a peripheral pattern. HLA-B15 should be considered in addition to HLA-B27 when diagnosing patients with SpA according to ASAS criteria. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

mTORC1 pathway disruption abrogates the effects of the ciliary neurotrophic factor on energy balance and hypothalamic neuroinflammation.

PubMed

André, Caroline; Catania, Caterina; Remus-Borel, Julie; Ladeveze, Elodie; Leste-Lasserre, Thierry; Mazier, Wilfrid; Binder, Elke; Gonzales, Delphine; Clark, Samantha; Guzman-Quevedo, Omar; Abrous, Djoher Nora; Layé, Sophie; Cota, Daniela

2018-05-01

Ciliary neurotrophic factor (CNTF) potently decreases food intake and body weight in diet-induced obese mice by acting through neuronal circuits and pathways located in the arcuate nucleus (ARC) of the hypothalamus. CNTF also exerts pro-inflammatory actions within the brain. Here we tested whether CNTF modifies energy balance by inducing inflammatory responses in the ARC and whether these effects depend upon the mechanistic target of rapamycin complex 1 (mTORC1) pathway, which regulates both energy metabolism and inflammation. To this purpose, chow- and high fat diet (HFD)- fed mice lacking the S6 kinase 1 (S6K1 -/- ), a downstream target of mTORC1, and their wild-type (WT) littermates received 12 days continuous intracerebroventricular (icv) infusion of the CNTF analogue axokine (CNTF Ax15 ). Behavioral, metabolic and molecular effects were evaluated. Central chronic administration of CNTF Ax15 decreased body weight and feed efficiency in WT mice only, when fed HFD, but not chow. These metabolic effects correlated with increased number of iba-1 positive microglia specifically in the ARC and were accompanied by significant increases of IL-1β and TNF-α mRNA expression in the hypothalamus. Hypothalamic iNOS and SOCS3 mRNA, molecular markers of pro-inflammatory response, were also increased by CNTF Ax15 . All these changes were absent in S6K1 -/- mice. This study reveals that CNTF Ax15 requires a functional S6K1 to modulate energy balance and hypothalamic inflammation in a diet-dependent fashion. Further investigations should determine whether S6K1 is a suitable target for the treatment of pathologies characterized by a high neuroinflammatory state. Copyright © 2018 Elsevier Inc. All rights reserved.

The profiles of gamma-H2AX along with ATM/DNA-PKcs activation in the lymphocytes and granulocytes of rat and human blood exposed to gamma rays.

PubMed

Wang, Jing; Yin, Lina; Zhang, Junxiang; Zhang, Yaping; Zhang, Xuxia; Ding, Defang; Gao, Yun; Li, Qiang; Chen, Honghong

2016-08-01

Establishing a rat model suitable for γ-H2AX biodosimeter studies has important implications for dose assessment of internal radionuclide contamination in humans. In this study, γ-H2AX, p-ATM and p-DNA-PKcs foci were enumerated using immunocytofluorescence method, and their protein levels were measured by Western blot in rat blood lymphocytes and granulocytes exposed to γ-rays compared with human blood lymphocytes and granulocytes. It was found that DNA double-strand break repair kinetics and linear dose responses in rat lymphocytes were similar to those observed in the human counterparts. Moreover, radiation induced clear p-ATM and p-DNA-PKcs foci formation and an increase in ratio of co-localization of p-ATM or p-DNA-PKcs with γ-H2AX foci in rat lymphocytes similar to those of human lymphocytes. The level of γ-H2AX protein in irradiated rat and human lymphocytes was significantly reduced by inhibitors of ATM and DNA-PKcs. Surprisingly, unlike human granulocytes, rat granulocytes with DNA-PKcs deficiency displayed a rapid accumulation, but delayed disappearance of γ-H2AX foci with essentially no change from 10 h to 48 h post-irradiation. Furthermore, inhibition of ATM activity in rat granulocytes also decreased radiation-induced γ-H2AX foci formation. In comparison, human granulocytes showed no response to irradiation regarding γ-H2AX, p-ATM or p-DNA-PKcs foci. Importantly, incidence of γ-H2AX foci in lymphocytes after total-body radiation of rats was consistent with that of in vitro irradiation of rat lymphocytes. These findings show that rats are a useful in vivo model for validation of γ-H2AX biodosimetry for dose assessment in humans. ATM and DNA-PKcs participate together in DSB repair in rat lymphocytes similar to that of human lymphocytes. Further, rat granulocytes, which have the characteristic of delayed disappearance of γ-H2AX foci in response to radiation, may be a useful experimental system for biodosimetry studies.

Betalactam antibiotics affect human dendritic cells maturation through MAPK/NF-kB systems. Role in allergic reactions to drugs

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

Lopez, Soledad; Department of Medical Biochemistry, Molecular Biology and Immunology, The University of Seville Medical School, Seville; Gomez, Enrique

The mechanisms leading to drug allergy in predisposed patients, especially those related to T-cell-mediated drug hypersensitivity, are not well understood. A key event in allergic reactions to drugs is the maturation process undergone by dendritic cells (DCs). Although amoxicillin (AX) has been reported to interact and maturate DCs from patients with AX-induced delayed-type hypersensitivity, the cell signaling pathways related to AX-mediated DC maturation have not been elucidated. We sought to determine the role of the MAPK and NF-κΒ pathways on AX-induced DC maturation and functional status. For that purpose, in monocyte-derived-DCs from AX-delayed allergic patients and tolerant subjects, we analyzedmore » the activation pattern of p38MAPK, JNK, and ERK signaling and the NF-κB, maturation markers as well as endocytosis and allostimulatory capacities driven by AX-stimulated-DCs. Our data reveal that AX induces an increase in the phosphorylation levels of the three MAPKsand activated NF-κB in DCs from allergic patients. Moreover, the inhibition of these pathways prevents the up-regulation of surface molecules induced by AX. Additionally, we observed that the allostimulatory capacity and the endocytosis down-regulation in AX-stimulated-DCs from allergic patients depend on JNK and NF-κB activities. Taken together, our data shed light for the first time on the main signaling pathways involved in DC maturation from AX-delayed allergic patient. - Highlights: • The cell signaling pathways related to drug-mediated DC maturation were tested. • Amoxicillin induces activation of MAPK and NF-κB in DCs from allergic patients. • The inhibition of these pathways prevents the up-regulation of DC surface molecules. • Their allostimulatory and endocytosis capacities depend on JNK and NF-κB activities. • The low involvement of p38-MAPK could be the cause of an incomplete DC maturation.« less

Effect of suppression of arabinoxylan synthetic genes in wheat endosperm on chain length of arabinoxylan and extract viscosity.

PubMed

Freeman, Jackie; Lovegrove, Alison; Wilkinson, Mark David; Saulnier, Luc; Shewry, Peter Robert; Mitchell, Rowan Andrew Craig

2016-01-01

Arabinoxylan (AX) is the dominant component within wheat (Triticum aestivum L.) endosperm cell walls, accounting for 70% of the polysaccharide. The viscosity of aqueous extracts from wheat grain is a key trait influencing the processing for various end uses, and this is largely determined by the properties of endosperm AX. We have previously shown dramatic effects on endosperm AX in transgenic wheat by down-regulating either TaGT43_2 or TaGT47_2 genes (orthologues to IRX9 and IRX10 in Arabidopsis, respectively) implicated in AX chain extension and the TaXAT1 gene responsible for monosubstitution by 3-linked arabinose. Here, we use these transgenic lines to investigate the relationship between amounts of AX in soluble and insoluble fractions, the chain-length distribution of these measured by intrinsic viscosity and the overall effect on extract viscosity. In transgenic lines expressing either the TaGT43_2 or TaGT47_2 RNAi transgenes, the intrinsic viscosities of water-extractable (WE-AX) and of a water-insoluble alkaline-extracted fraction (AE-AX) were decreased by between 10% and 50% compared to control lines. In TaXAT1 RNAi lines, there was a 15% decrease in intrinsic viscosity of WE-AX but no consistent effect on that of AE-AX. All transgenic lines showed decreases in extract viscosity with larger effects in TaGT43_2 and TaGT47_2 RNAi lines (by up to sixfold) than in TaXAT1 RNAi lines (by twofold). These effects were explained by the decreases in amount and chain length of WE-AX, with decreases in amount having the greater influence. Extract viscosity from wheat grain can therefore be greatly decreased by suppression of single gene targets. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

H2AX foci in late S/G2- and M-phase cells after hydroxyurea- and aphidicolin-induced DNA replication stress in Vicia.

PubMed

Rybaczek, Dorota; Bodys, Aleksandra; Maszewski, Janusz

2007-09-01

Immunocytochemistry using alpha-phospho-H2AX antibodies shows that hydroxyurea (HU), an inhibitor of ribonucleotide reductase, and aphidicolin (APH), an inhibitor of DNA-polymerases alpha and delta, may promote formation of phospho-H2AX foci in late S/G2-phase cells in root meristems of Vicia faba. Although fluorescent foci spread throughout the whole area of nucleoplasm, large phospho-H2AX aggregates in HU-treated cells allocate mainly in perinucleolar regions. A strong tendency of ATR/ATM-dependent phospho-Chk1S317 kinase to focus in analogous compartments, as opposed to phospho-Chk2T68 and to both effector kinases in APH-treated cells, may suggest that selected elements of the intra-S-phase cell cycle checkpoints share overlapping locations with DNA repair factors known to concentrate in phospho-H2AX aggregates. APH-induced phosphorylation of H2AX exhibits little or no overlap with the areas positioned close to nucleoli. Following G2-M transition of the HU- and APH-pretreated cells, altered chromatin structures are still discernible as large phospho-H2AX foci in the vicinity of chromosomes. Both in HU- and APH-treated roots, immunofluorescence analysis revealed a dominant fraction of small foci and a less frequent population of large phospho-H2AX aggregates, similar to those observed in animal cells exposed to ionizing radiation. The extent of H2AX phosphorylation has been found considerably reduced in root meristem cells treated with HU and caffeine. The frequencies of phospho-H2AX foci observed during mitosis and caffeine-mediated premature chromosome condensation (PCC) suggest that there may be functional links between the checkpoint mechanisms that control genome integrity and those activities which operate throughout the unperturbed mitosis in plants.

Hydroxycinnamic acid bound arabinoxylans from millet brans-structural features and antioxidant activity.

PubMed

Bijalwan, Vandana; Ali, Usman; Kesarwani, Atul Kumar; Yadav, Kamalendra; Mazumder, Koushik

2016-07-01

Hydroxycinnamic acid bound arabinoxylans (HCA-AXs) were extracted from brans of five Indian millet varieties and response surface methodology was used to optimize the extraction conditions. The optimal condition to obtain highest yield of millet HCA-AXs was determined as follows: time 61min, temperature 66°C, ratio of solvent to sample 12ml/g. Linkage analysis indicated that hydroxycinnamic acid bound arabinoxylan from kodo millet (KM-HCA-AX) contained comparatively low branched arabinoxylan consisting of 14.6% mono-substituted, 1.2% di-substituted and 41.2% un-substituted Xylp residues. The HPLC analysis of millet HCA-AXs showed significant variation in the content of three major bound hydroxycinnamic acids (caffeic, p-coumaric and ferulic acid). The antioxidant activity of millet HCA-AXs were evaluated using three in vitro assay methods (DPPH, FRAP and β-carotene linoleate emulsion assays) which suggested both phenolic acid composition and structural characteristics of arabinoxylans could be correlated to their antioxidant potential, the detailed structural analysis revealed that low substituted KM-HCA-AX exhibited relatively higher antioxidant activity compared to other medium and highly substituted HCA-AXs from finger (FM), proso (PM), barnyard (BM) and foxtail (FOXM) millet. Copyright © 2016. Published by Elsevier B.V.

Super-Resolution Localization Microscopy of γ-H2AX and Heterochromatin after Folate Deficiency.

PubMed

Bach, Margund; Savini, Claudia; Krufczik, Matthias; Cremer, Christoph; Rösl, Frank; Hausmann, Michael

2017-08-08

Folate is an essential water-soluble vitamin in food and nutrition supplements. As a one-carbon source, it is involved in many central regulatory processes, such as DNA, RNA, and protein methylation as well as DNA synthesis and repair. Deficiency in folate is considered to be associated with an increased incidence of several malignancies, including cervical cancer that is etiologically linked to an infection with "high-risk" human papilloma viruses (HPV). However, it is still not known how a recommended increase in dietary folate after its deprivation affects the physiological status of cells. To study the impact of folate depletion and its subsequent reconstitution in single cells, we used quantitative chromatin conformation measurements obtained by super-resolution fluorescence microscopy, i.e., single molecule localization microscopy (SMLM). As a read-out, we examined the levels and the (re)positioning of γ-H2AX tags and histone H3K9me3 heterochromatin tags after immunostaining in three-dimensional (3D)-conserved cell nuclei. As model, we used HPV16 positive immortalized human keratinocytes that were cultivated under normal, folate deficient, and reconstituted conditions for different periods of time. The results were compared to cells continuously cultivated in standard folate medium. After 13 weeks in low folate, an increase in the phosphorylation of the histone H2AX was noted, indicative of an accumulation of DNA double strand breaks. DNA repair activity represented by the formation of those γ-H2AX clusters was maintained during the following 15 weeks of examination. However, the clustered arrangements of tags appeared to relax in a time-dependent manner. Parallel to the repair activity, the chromatin methylation activity increased as detected by H3K9me3 tags. The progress of DNA double strand repair was accompanied by a reduction of the detected nucleosome density around the γ-H2AX clusters, suggesting a shift from hetero- to euchromatin to allow access to the repair machinery. In conclusion, these data demonstrated a folate-dependent repair activity and chromatin re-organization on the SMLM nanoscale level. This offers new opportunities to further investigate folate-induced chromatin re-organization and the associated mechanisms.

Targeting Protein for Xenopus Kinesin-like Protein 2 (TPX2) Regulates γ-Histone 2AX (γ-H2AX) Levels upon Ionizing Radiation*

PubMed Central

Neumayer, Gernot; Helfricht, Angela; Shim, Su Yeon; Le, Hoa Thi; Lundin, Cecilia; Belzil, Camille; Chansard, Mathieu; Yu, Yaping; Lees-Miller, Susan P.; Gruss, Oliver J.; van Attikum, Haico; Helleday, Thomas; Nguyen, Minh Dang

2012-01-01

The microtubule-associated protein targeting protein for Xenopus kinesin-like protein 2 (TPX2) plays a key role in spindle assembly and is required for mitosis in human cells. In interphase, TPX2 is actively imported into the nucleus to prevent its premature activity in microtubule organization. To date, no function has been assigned to nuclear TPX2. We now report that TPX2 plays a role in the cellular response to DNA double strand breaks induced by ionizing radiation. Loss of TPX2 leads to inordinately strong and transient accumulation of ionizing radiation-dependent Ser-139-phosphorylated Histone 2AX (γ-H2AX) at G0 and G1 phases of the cell cycle. This is accompanied by the formation of increased numbers of high intensity γ-H2AX ionizing radiation-induced foci. Conversely, cells overexpressing TPX2 have reduced levels of γ-H2AX after ionizing radiation. Consistent with a role for TPX2 in the DNA damage response, we found that the protein accumulates at DNA double strand breaks and associates with the mediator of DNA damage checkpoint 1 (MDC1) and the ataxia telangiectasia mutated (ATM) kinase, both key regulators of γ-H2AX amplification. Pharmacologic inhibition or depletion of ATM or MDC1, but not of DNA-dependent protein kinase (DNA-PK), antagonizes the γ-H2AX phenotype caused by TPX2 depletion. Importantly, the regulation of γ-H2AX signals by TPX2 is not associated with apoptosis or the mitotic functions of TPX2. In sum, our study identifies a novel and the first nuclear function for TPX2 in the cellular responses to DNA damage. PMID:23045526

A Genome Wide Association Study of arabinoxylan content in 2-row spring barley grain

PubMed Central

Hassan, Ali Saleh; Houston, Kelly; Lahnstein, Jelle; Shirley, Neil; Schwerdt, Julian G.; Gidley, Michael J.; Waugh, Robbie; Little, Alan

2017-01-01

In barley endosperm arabinoxylan (AX) is the second most abundant cell wall polysaccharide and in wheat it is the most abundant polysaccharide in the starchy endosperm walls of the grain. AX is one of the main contributors to grain dietary fibre content providing several health benefits including cholesterol and glucose lowering effects, and antioxidant activities. Due to its complex structural features, AX might also affect the downstream applications of barley grain in malting and brewing. Using a high pressure liquid chromatography (HPLC) method we quantified AX amounts in mature grain in 128 spring 2-row barley accessions. Amounts ranged from ~ 5.2 μg/g to ~ 9 μg/g. We used this data for a Genome Wide Association Study (GWAS) that revealed three significant quantitative trait loci (QTL) associated with grain AX levels which passed a false discovery threshold (FDR) and are located on two of the seven barley chromosomes. Regions underlying the QTLs were scanned for genes likely to be involved in AX biosynthesis or turnover, and strong candidates, including glycosyltransferases from the GT43 and GT61 families and glycoside hydrolases from the GH10 family, were identified. Phylogenetic trees of selected gene families were built based on protein translations and were used to examine the relationship of the barley candidate genes to those in other species. Our data reaffirms the roles of existing genes thought to contribute to AX content, and identifies novel QTL (and candidate genes associated with them) potentially influencing the AX content of barley grain. One potential outcome of this work is the deployment of highly associated single nucleotide polymorphisms markers in breeding programs to guide the modification of AX abundance in barley grain. PMID:28771585

Application of model bread baking in the examination of arabinoxylan-protein complexes in rye bread.

PubMed

Buksa, Krzysztof

2016-09-05

The changes in molecular mass of arabinoxylan (AX) and protein caused by bread baking process were examined using a model rye bread. Instead of the normal flour, the dough contained starch, water-extractable AX and protein which were isolated from rye wholemeal. From the crumb of selected model breads, starch was removed releasing AX-protein complexes, which were further examined by size exclusion chromatography. On the basis of the research, it was concluded that optimum model mix can be composed of 3-6% AX and 3-6% rye protein isolate at 94-88% of rye starch meaning with the most similar properties to low extraction rye flour. Application of model rye bread allowed to examine the interactions between AX and proteins. Bread baked with a share of AX, rye protein and starch, from which the complexes of the highest molar mass were isolated, was characterized by the strongest structure of the bread crumb. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ankylosing Spondylitis versus Nonradiographic Axial Spondyloarthritis: Comparison of Tumor Necrosis Factor Inhibitor Effectiveness and Effect of HLA-B27 Status. An Observational Cohort Study from the Nationwide DANBIO Registry.

PubMed

Glintborg, Bente; Sørensen, Inge J; Østergaard, Mikkel; Dreyer, Lene; Mohamoud, Abdiweli A; Krogh, Niels S; Hendricks, Oliver; Andersen, Lis S; Raun, Johnny L; Kowalski, Marcin R; Danielsen, Laura; Pelck, Randi; Nordin, Henrik; Pedersen, Jens K; Kraus, Dorte G A; Christensen, Susan R; Hansen, Inger M J; Esbesen, Jakob; Schlemmer, Annette; Loft, Anne G; Al Chaer, Nabil; Salomonsen, Lone; Hetland, Merete L

2017-01-01

To compare baseline disease activity and treatment effectiveness in biologic-naive patients with nonradiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) who initiate tumor necrosis factor inhibitor (TNFi) treatment and to study the role of potential confounders (e.g., HLA-B27 status). Observational cohort study based on prospectively registered data in the nationwide DANBIO registry. We used Kaplan-Meier plots, Cox, and logistic regression analyses to study the effect of diagnosis (nr-axSpA vs AS) and potential confounders (sex/age/start yr/HLA-B27/disease duration/TNFi-type/smoking/baseline disease activity) on TNFi adherence and response [e.g., Bath Ankylosing Spondylitis Activity Index (BASDAI) 50%/20 mm]. The study included 1250 TNFi-naive patients with axSpA (29% nr-axSpA, 50% AS, 21% lacked radiographs of sacroiliac joints). Patients with nr-axSpA were more frequently women (50%/27%) and HLA-B27-negative (85/338 = 25%), compared to AS (81/476 = 17%; p < 0.01). At TNFi start patients with nr-axSpA had higher visual analog scale scores [median (quartiles)] for pain: 72 mm (55-84)/65 mm (48-77); global: 76 mm (62-88)/68 mm (50-80); fatigue: 74 mm (55-85)/67 mm (50-80); and BASDAI: 64 (54-77)/59 (46-71); all p < 0.01. However, patients with nr-axSpA had lower C-reactive protein: 7 mg/l (3-17)/11 mg/l (5-22); and BAS Metrology Index: 20 (10-40)/40 (20-50); all p < 0.01. Median (95% CI) treatment adherence was poorer in nr-axSpA than in AS: 1.59 years (1.15-2.02) versus 3.67 years (2.86-4.49), p < 0.0001; but only in univariate and not confounder-adjusted analyses (p > 0.05). Response rates were similar in AS and nr-axSpA (p > 0.05). HLA-B27 negativity was associated with poorer treatment adherence [HLA-B27 negative/positive, nr-axSpA: HR 1.74 (1.29-2.36), AS: HR 2.04 (1.53-2.71), both p < 0.0001]; and lower response rates (nr-axSpA: 18/61 = 30% vs 93/168 = 55%; AS: 17/59 = 29% vs 157/291 = 54%, both p < 0.05). In this nationwide cohort, patients with nr-axSpA had higher subjective disease activity at start of first TNFi treatment, but similar outcomes to patients with AS after confounder adjustment. HLA-B27 positivity was associated with better outcomes irrespective of axSpA subdiagnosis.

SoAx: A generic C++ Structure of Arrays for handling particles in HPC codes

NASA Astrophysics Data System (ADS)

Homann, Holger; Laenen, Francois

2018-03-01

The numerical study of physical problems often require integrating the dynamics of a large number of particles evolving according to a given set of equations. Particles are characterized by the information they are carrying such as an identity, a position other. There are generally speaking two different possibilities for handling particles in high performance computing (HPC) codes. The concept of an Array of Structures (AoS) is in the spirit of the object-oriented programming (OOP) paradigm in that the particle information is implemented as a structure. Here, an object (realization of the structure) represents one particle and a set of many particles is stored in an array. In contrast, using the concept of a Structure of Arrays (SoA), a single structure holds several arrays each representing one property (such as the identity) of the whole set of particles. The AoS approach is often implemented in HPC codes due to its handiness and flexibility. For a class of problems, however, it is known that the performance of SoA is much better than that of AoS. We confirm this observation for our particle problem. Using a benchmark we show that on modern Intel Xeon processors the SoA implementation is typically several times faster than the AoS one. On Intel's MIC co-processors the performance gap even attains a factor of ten. The same is true for GPU computing, using both computational and multi-purpose GPUs. Combining performance and handiness, we present the library SoAx that has optimal performance (on CPUs, MICs, and GPUs) while providing the same handiness as AoS. For this, SoAx uses modern C++ design techniques such template meta programming that allows to automatically generate code for user defined heterogeneous data structures.

Survival Fraction at 2 Gy and γH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities

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

Pouliliou, Stamatia E.; Lialiaris, Theodoros S.; Dimitriou, Thespis

Purpose: Predictive assays for acute radiation toxicities would be clinically relevant in radiation oncology. We prospectively examined the predictive role of the survival fraction at 2 Gy (SF2) and of γH2AX (double-strand break [DSB] DNA marker) expression kinetics in peripheral blood mononuclear cells (PBMCs) from cancer patients before radiation therapy. Methods and Materials: SF2 was measured with Trypan Blue assay in the PBMCs from 89 cancer patients undergoing radiation therapy at 4 hours (SF2{sub [4h]}) and 24 hours (SF2{sub [24h]}) after ex vivo irradiation. Using Western blot analysis and band densitometry, we further assessed the expression of γH2AX in PBMC DNA at 0 hours, 30 minutes,more » and 4 hours (33 patients) and 0 hour, 4 hours, and 24 hours (56 patients), following ex vivo irradiation with 2 Gy. Appropriate ratios were used to characterize each patient, and these were retrospectively correlated with early radiation therapy toxicity grade. Results: The SF2{sub (4h)} was inversely correlated with the toxicity grade (P=.006). The γH2AX-ratio{sub (30min)} (band density of irradiated/non-irradiated cells at 30 minutes) revealed, similarly, a significant inverse association (P=.0001). The DSB DNA repair rate from 30 minutes to 4 hours, calculated as the relative RγH2AX-ratio (γH2AX-ratio{sub (4h)}/γH2AX-ratio{sub (30min)}) showed a significant direct association with high toxicity grade (P=.01). Conclusions: Our results suggest that SF2 is a significant radiation sensitivity index for patients undergoing radiation therapy. γH2AX Western blot densitometry analysis provided 2 important markers of normal tissue radiation sensitivity. Low γH2AX expression at 30 minutes was linked with high toxicity grade, suggesting that poor γH2AX repair activity within a time frame of 30 minutes after irradiation predicts for poor radiation tolerance. On the other hand, rapid γH2AX content restoration at 4 hours after irradiation, compatible with efficient DSB repair ability, predicts for increased radiation tolerance.« less

Indicators of replicative damage in equine tendon fibroblast monolayers

PubMed Central

2013-01-01

Background Superficial digital flexor tendon (SDFT) injuries of horses usually follow cumulative matrix microdamage; it is not known why the reparative abilities of tendon fibroblasts are overwhelmed or subverted. Relevant in vitro studies of this process require fibroblasts not already responding to stresses caused by the cell culture protocols. We investigated indicators of replicative damage in SDFT fibroblast monolayers, effects of this on their reparative ability, and measures that can be taken to reduce it. Results We found significant evidence of replicative stress, initially observing consistently large numbers of binucleate (BN) cells. A more variable but prominent feature was the presence of numerous gammaH2AX (γH2AX) puncta in nuclei, this being a histone protein that is phosphorylated in response to DNA double-stranded breaks (DSBs). Enrichment for injury detection and cell cycle arrest factors (p53 (ser15) and p21) occurred most frequently in BN cells; however, their numbers did not correlate with DNA damage levels and it is likely that the two processes have different causative mechanisms. Such remarkable levels of injury and binucleation are usually associated with irradiation, or treatment with cytoskeletal-disrupting agents. Both DSBs and BN cells were greatest in subconfluent (replicating) monolayers. The DNA-damaged cells co-expressed the replication markers TPX2/repp86 and centromere protein F. Once damaged in the early stages of culture establishment, fibroblasts continued to express DNA breaks with each replicative cycle. However, significant levels of cell death were not measured, suggesting that DNA repair was occurring. Comet assays showed that DNA repair was delayed in proportion to levels of genotoxic stress. Conclusions Researchers using tendon fibroblast monolayers should assess their “health” using γH2AX labelling. Continued use of early passage cultures expressing initially high levels of γH2AX puncta should be avoided for mechanistic studies and ex-vivo therapeutic applications, as this will not be resolved with further replicative cycling. Low density cell culture should be avoided as it enriches for both DNA damage and mitotic defects (polyploidy). As monolayers differing only slightly in baseline DNA damage levels showed markedly variable responses to a further injury, studies of effects of various stressors on tendon cells must be very carefully controlled. PMID:24025445

Coexpression of the High Molecular Weight Glutenin Subunit 1Ax1 and Puroindoline Improves Dough Mixing Properties in Durum Wheat (Triticum turgidum L. ssp. durum)

PubMed Central

Li, Xiaoyan; Xiao, Xin; Sun, Fusheng; Wang, Cheng; Hu, Wei; Feng, Zhijuan; Chang, Junli; Chen, Mingjie; Wang, Yuesheng; Li, Kexiu; Yang, Guangxiao; He, Guangyuan

2012-01-01

Wheat end-use quality mainly derives from two interrelated characteristics: the compositions of gluten proteins and grain hardness. The composition of gluten proteins determines dough rheological properties and thus confers the unique viscoelastic property on dough. One group of gluten proteins, high molecular weight glutenin subunits (HMW-GS), plays an important role in dough functional properties. On the other hand, grain hardness, which influences the milling process of flour, is controlled by Puroindoline a (Pina) and Puroindoline b (Pinb) genes. However, little is known about the combined effects of HMW-GS and PINs on dough functional properties. In this study, we crossed a Pina-expressing transgenic line with a 1Ax1-expressing line of durum wheat and screened out lines coexpressing 1Ax1 and Pina or lines expressing either 1Ax1 or Pina. Dough mixing analysis of these lines demonstrated that expression of 1Ax1 improved both dough strength and over-mixing tolerance, while expression of PINA detrimentally affected the dough resistance to extension. In lines coexpressing 1Ax1 and Pina, faster hydration of flour during mixing was observed possibly due to the lower water absorption and damaged starch caused by PINA expression. In addition, expression of 1Ax1 appeared to compensate the detrimental effect of PINA on dough resistance to extension. Consequently, coexpression of 1Ax1 and PINA in durum wheat had combined effects on dough mixing behaviors with a better dough strength and resistance to extension than those from lines expressing either 1Ax1 or Pina. The results in our study suggest that simultaneous modulation of dough strength and grain hardness in durum wheat could significantly improve its breadmaking quality and may not even impair its pastamaking potential. Therefore, coexpression of 1Ax1 and PINA in durum wheat has useful implications for breeding durum wheat with dual functionality (for pasta and bread) and may improve the economic values of durum wheat. PMID:23185532

Coexpression of the high molecular weight glutenin subunit 1Ax1 and puroindoline improves dough mixing properties in durum wheat (Triticum turgidum L. ssp. durum).

PubMed

Li, Yin; Wang, Qiong; Li, Xiaoyan; Xiao, Xin; Sun, Fusheng; Wang, Cheng; Hu, Wei; Feng, Zhijuan; Chang, Junli; Chen, Mingjie; Wang, Yuesheng; Li, Kexiu; Yang, Guangxiao; He, Guangyuan

2012-01-01

Wheat end-use quality mainly derives from two interrelated characteristics: the compositions of gluten proteins and grain hardness. The composition of gluten proteins determines dough rheological properties and thus confers the unique viscoelastic property on dough. One group of gluten proteins, high molecular weight glutenin subunits (HMW-GS), plays an important role in dough functional properties. On the other hand, grain hardness, which influences the milling process of flour, is controlled by Puroindoline a (Pina) and Puroindoline b (Pinb) genes. However, little is known about the combined effects of HMW-GS and PINs on dough functional properties. In this study, we crossed a Pina-expressing transgenic line with a 1Ax1-expressing line of durum wheat and screened out lines coexpressing 1Ax1 and Pina or lines expressing either 1Ax1 or Pina. Dough mixing analysis of these lines demonstrated that expression of 1Ax1 improved both dough strength and over-mixing tolerance, while expression of PINA detrimentally affected the dough resistance to extension. In lines coexpressing 1Ax1 and Pina, faster hydration of flour during mixing was observed possibly due to the lower water absorption and damaged starch caused by PINA expression. In addition, expression of 1Ax1 appeared to compensate the detrimental effect of PINA on dough resistance to extension. Consequently, coexpression of 1Ax1 and PINA in durum wheat had combined effects on dough mixing behaviors with a better dough strength and resistance to extension than those from lines expressing either 1Ax1 or Pina. The results in our study suggest that simultaneous modulation of dough strength and grain hardness in durum wheat could significantly improve its breadmaking quality and may not even impair its pastamaking potential. Therefore, coexpression of 1Ax1 and PINA in durum wheat has useful implications for breeding durum wheat with dual functionality (for pasta and bread) and may improve the economic values of durum wheat.

A new hand-held microfluidic cytometer for evaluating irradiation damage by analysis of the damaged cells distribution.

PubMed

Wang, Junsheng; Fan, Zhiqiang; Zhao, Yile; Song, Younan; Chu, Hui; Song, Wendong; Song, Yongxin; Pan, Xinxiang; Sun, Yeqing; Li, Dongqing

2016-03-17

Space radiation brings uneven damages to cells. The detection of the distribution of cell damage plays a very important role in radiation medicine and the related research. In this paper, a new hand-held microfluidic flow cytometer was developed to evaluate the degree of radiation damage of cells. The device we propose overcomes the shortcomings (e.g., large volume and high cost) of commercial flow cytometers and can evaluate the radiation damage of cells accurately and quickly with potential for onsite applications. The distribution of radiation-damaged cells is analyzed by a simultaneous detection of immunofluorescence intensity of γ-H2AX and resistance pulse sensor (RPS) signal. The γ-H2AX fluorescence intensity provides information of the degree of radiation damage in cells. The ratio of the number of cells with γ-H2AX fluorescence signals to the total numbers of cells detected by RPS indicates the percentage of the cells that are damaged by radiation. The comparison experiment between the developed hand-held microfluidic flow cytometer and a commercial confocal microscope indicates a consistent and comparable detection performance.

A new hand-held microfluidic cytometer for evaluating irradiation damage by analysis of the damaged cells distribution

NASA Astrophysics Data System (ADS)

Wang, Junsheng; Fan, Zhiqiang; Zhao, Yile; Song, Younan; Chu, Hui; Song, Wendong; Song, Yongxin; Pan, Xinxiang; Sun, Yeqing; Li, Dongqing

2016-03-01

Space radiation brings uneven damages to cells. The detection of the distribution of cell damage plays a very important role in radiation medicine and the related research. In this paper, a new hand-held microfluidic flow cytometer was developed to evaluate the degree of radiation damage of cells. The device we propose overcomes the shortcomings (e.g., large volume and high cost) of commercial flow cytometers and can evaluate the radiation damage of cells accurately and quickly with potential for onsite applications. The distribution of radiation-damaged cells is analyzed by a simultaneous detection of immunofluorescence intensity of γ-H2AX and resistance pulse sensor (RPS) signal. The γ-H2AX fluorescence intensity provides information of the degree of radiation damage in cells. The ratio of the number of cells with γ-H2AX fluorescence signals to the total numbers of cells detected by RPS indicates the percentage of the cells that are damaged by radiation. The comparison experiment between the developed hand-held microfluidic flow cytometer and a commercial confocal microscope indicates a consistent and comparable detection performance.

Astaxanthin preparation by fermentation of esters from Haematococcus pluvialis algal extracts with Stenotrophomonas species.

PubMed

Dong, Hao; Li, Xuemin; Xue, Changhu; Mao, Xiangzhao

2016-05-01

Natural astaxanthin (Ax) is an additive that is widely used because of its beneficial biochemical functions. However, the methods used to produce free Ax have drawbacks. Chemical saponification methods produce several by-products, and lipase-catalyzed hydrolysis methods are not cost effective. In this study, a bacterial strain of Stenotrophomonas sp. was selected to enzymatically catalyze the saponification of Ax esters to produce free all-trans-Ax. Through single-factor experiments and a Box-Behnken design, the optimal fermentation conditions were determined as follows: a seed culture age of 37.79 h, an inoculum concentration of 5.92%, and an initial broth pH of 6.80. Under these conditions, a fermentation curve was drawn, and the optimal fermentation time was shown to be 60 h. At 60 h, the degradation rate of the Ax esters was 98.08%, and the yield of free all-trans-Ax was 50.130 μg/mL. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:649-656, 2016. © 2016 American Institute of Chemical Engineers.

Optimization and development of a SPE-HPLC-UV method to determine astaxanthin in Saccharina japonica.

PubMed

Zhou, Jun; Bi, Wentao; Row, Kyung Ho

2011-04-01

An effective and accurate method including extraction, saponification, and separation was developed to determine astaxanthin (AX) in Saccharina japonica. The optimal extraction conditions with different solvents were investigated. 29.30 μg/g of AX was extracted from dry Saccharina japonica powder by solvent. After subsequent saponification, the extracted amount of AX was increased to 37.26 μg/g. Furthermore, 3 different ionic liquid-based silicas were prepared as sorbents for the solid phase extraction of AX from the extract. By comparing the adsorption isotherms of AX on different ionic liquid-based silicas, suitable sorbent was successfully selected and applied for separation of AX from extract. Astaxanthin, in 3 main forms (free, monoesters, and diesters), can be obtained from marine plants and animals. By extraction with subsequent saponification, the astaxanthin was extracted from Saccharina japonica. And then, ionic liquid-based silicas were used to separate the astaxanthin from the extract solution. This method can be widely applied for determination, or even industrial separation and purification of astaxanthin from many other algae.

Redox and Chemical Activities of the Hemes in the Sulfur Oxidation Pathway Enzyme SoxAX*

PubMed Central

Bradley, Justin M.; Marritt, Sophie J.; Kihlken, Margaret A.; Haynes, Kate; Hemmings, Andrew M.; Berks, Ben C.; Cheesman, Myles R.; Butt, Julea N.

2012-01-01

SoxAX enzymes couple disulfide bond formation to the reduction of cytochrome c in the first step of the phylogenetically widespread Sox microbial sulfur oxidation pathway. Rhodovulum sulfidophilum SoxAX contains three hemes. An electrochemical cell compatible with magnetic circular dichroism at near infrared wavelengths has been developed to resolve redox and chemical properties of the SoxAX hemes. In combination with potentiometric titrations monitored by electronic absorbance and EPR, this method defines midpoint potentials (Em) at pH 7.0 of approximately +210, −340, and −400 mV for the His/Met, His/Cys−, and active site His/CysS−-ligated heme, respectively. Exposing SoxAX to S2O42−, a substrate analog with Em ∼−450 mV, but not Eu(II) complexed with diethylene triamine pentaacetic acid (Em ∼−1140 mV), allows cyanide to displace the cysteine persulfide (CysS−) ligand to the active site heme. This provides the first evidence for the dissociation of CysS− that has been proposed as a key event in SoxAX catalysis. PMID:23060437

ERPs evidence for the relationship between fluid intelligence and cognitive control.

PubMed

Lu, Di; Zhang, Haoyun; Kang, Chunyan; Guo, Taomei

2016-04-13

The relationship between two components of cognitive control, that is, proactive control and reactive control, and fluid intelligence was investigated by measuring 75 participants' event-related potentials in the AX version of the continuous performance test. The results showed that the mean amplitudes of N2 associated with the two components of cognitive control are highly correlated with fluid intelligence. Specifically, a larger N2 was shown in participants with higher fluid intelligence scores. No significant correlation was found in the peak latencies of the N2 and fluid intelligence. These results enrich our understanding of the relationship between cognitive control and fluid intelligence by using the N2 component as an index and also indicate that cognitive control may be a component of intelligence.

H2AX phosphorylation and DNA damage kinase activity are dispensable for herpes simplex virus replication.

PubMed

Botting, Carolyn; Lu, Xu; Triezenberg, Steven J

2016-01-27

Herpes simplex virus type 1 (HSV-1) can establish both lytic and latent infections in humans. The phosphorylation of histone H2AX, a common marker of DNA damage, during lytic infection by HSV-1 is well established. However, the role(s) of H2AX phosphorylation in lytic infection remain unclear. Following infection of human foreskin fibroblasts by HSV-1 or HSV-2, we assayed the phosphorylation of H2AX in the presence of inhibitors of transcription, translation, or viral DNA replication, or in the presence of inhibitors of ATM and ATR kinases (KU-55933 and VE-821, respectively). We also assayed viral replication in fibroblasts in the presence of the kinase inhibitors or siRNAs specific for ATM and ATR, as well as in cell lines deficient for either ATR or ATM. The expression of viral immediate-early and early proteins (including the viral DNA polymerase), but not viral DNA replication or late protein expression, were required for H2AX phosphorylation following HSV-1 infection. Inhibition of ATM kinase activity prevented HSV-stimulated H2AX phosphorylation but had only a minor effect on DNA replication and virus yield in HFF cells. These results differ from previous reports of a dramatic reduction in viral yield following chemical inhibition of ATM in oral keratinocytes or following infection of ATM(-/-) cells. Inhibition of the closely related kinase ATR (whether by chemical inhibitor or siRNA disruption) had no effect on H2AX phosphorylation and reduced viral DNA replication only moderately. During infection by HSV-2, H2AX phosphorylation was similarly dispensable but was dependent on both ATM activity and viral DNA replication. H2AX phosphorylation represents a cell type-specific and virus type-specific host response to HSV infection with little impact on viral infection.

γ-H2AX as a biomarker of DNA damage induced by ionizing radiation in human peripheral blood lymphocytes and artificial skin

NASA Astrophysics Data System (ADS)

Redon, Christophe E.; Dickey, Jennifer S.; Bonner, William M.; Sedelnikova, Olga A.

2009-04-01

Ionizing radiation (IR) exposure is inevitable in our modern society and can lead to a variety of deleterious effects including cancer and birth defects. A reliable, reproducible and sensitive assessment of exposure to IR and the individual response to that exposure would provide much needed information for the optimal treatment of each donor examined. We have developed a diagnostic test for IR exposure based on detection of the phosphorylated form of variant histone H2AX (γ-H2AX), which occurs specifically at sites of DNA double-strand breaks (DSBs). The cell responds to a nascent DSB through the phosphorylation of thousands of H2AX molecules flanking the damaged site. This highly amplified response can be visualized as a γ-H2AX focus in the chromatin that can be detected in situ with the appropriate antibody. Here we assess the usability of γ-H2AX focus formation as a possible biodosimeter for human exposure to IR using peripheral blood lymphocytes irradiated ex vivo and three-dimensional artificial models of human skin biopsies. In both systems, the tissues were exposed to 0.2-5 Gy, doses of IR that might be realistically encountered in various scenarios such as cancer radiotherapies or accidental exposure to radiation. Since the γ-H2AX response is maximal 30 min after exposure and declines over a period of hours as the cells repair the damage, we examined the time limitations of the useful detectability of γ-H2AX foci. We report that a linear response proportional to the initial radiation dose was obtained 48 and 24 h after exposure in blood samples and skin cells respectively. Thus, detection of γ-H2AX formation to monitor DNA damage in minimally invasive blood and skin tests could be useful tools to determine radiation dose exposure and analyze its effects on humans.

Detection of X-ray flares from AX J1714.1-3912, the unidentified source near RX J1713.7-3946

NASA Astrophysics Data System (ADS)

Miceli, Marco; Bamba, Aya

2018-04-01

Context. Molecular clouds are predicted to emit nonthermal X-rays when they are close to particle-accelerating supernova remnants (SNRs), and the hard X-ray source AX J1714.1-3912, near the SNR RX J1713.7-3946, has long been considered a candidate for diffuse nonthermal emission associated with cosmic rays diffusing from the remnant to a closeby molecular cloud. Aim. We aim at ascertaining the nature of this source by analyzing two dedicated X-ray observations performed with Suzaku and Chandra. Methods: We extracted images from the data in various energy bands, spectra, and light curves and studied the long-term evolution of the X-ray emission on the basis of the 4.5 yr time separation between the two observations. Results: We found that there is no diffuse emission associated with AX J1714.1-3912, which is instead the point-like source CXOU J171343.9-391205. We discovered rapid time variability (timescale 103 s), together with a high intrinsic absorption and a hard nonthermal spectrum (power law with photon index Γ 1.4). We also found that the X-ray flux of the source drops down by 1-2 orders of magnitude on a timescale of a few years. Conclusions: Our results suggest a possible association between AX J1714.1-3912 and a previously unknown supergiant fast X-ray transient, although further follow-up observations are necessary to prove this association definitively.

Cycle life machine for AX-5 space suit

NASA Technical Reports Server (NTRS)

Schenberger, Deborah S.

1990-01-01

In order to accurately test the AX-5 space suit, a complex series of motions needed to be performed which provided a unique opportunity for mechanism design. The cycle life machine design showed how 3-D computer images can enhance mechanical design as well as help in visualizing mechanisms before manufacturing them. In the early stages of the design, potential problems in the motion of the joint and in the four bar linkage system were resolved using CAD. Since these problems would have been very difficult and tedious to solve on a drawing board, they would probably not have been addressed prior to fabrication, thus limiting the final design or requiring design modification after fabrication.

Effect of mild temperature shift on poly(ADP-ribose) and γH2AX levels in cultured cells

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

Yamashita, Sachiko; Tanaka, Masakazu; Sato, Teruaki

Poly (ADP-ribose) (PAR) is rapidly synthesized by PAR polymerases (PARPs) upon activation by DNA single- and double-strand breaks. In this study, we examined the quantitative amount of PAR in HeLa cells cultured within the physiological temperatures below 41 °C for verification of the effect of shifting-up or -down the temperature from 37.0 °C on the DNA breaks, whether the temperature-shift caused breaks that could be monitored by the level of PAR. While PAR level did not change significantly when HeLa cells were cultured at 33.5 °C or 37.0 °C, it was significantly increased 2- and 3-fold when cells were cultured for 12 h andmore » 24 h, respectively, at 40.5 °C as compared to 37.0 °C. Similar to the results with HeLa cells, PAR level was increased 2-fold in CHO-K1 cells cultured at 40.5 °C for 24 h as compared to 37.0 °C. As the cellular levels of PAR polymerase1 (PARP1) and PAR glycohydrolase (PARG), a major degradation enzyme for PAR, did not seem to change significantly, this increase could be caused by activation of PARP1 by DNA strand breaks. In fact, γH2AX, claimed to be a marker of DNA double-strand breaks, was found in cell extracts of HeLa cells and CHO-K1 cells at elevated temperature vs. 37.0 °C, and these γH2AX signals were intensified in the presence of 3-aminobenzamide, a PARP inhibitor. The γH2AX immunohistochemistry results in HeLa cells were consistent with Western blot analyses. In HeLa cells, proliferation was significantly suppressed at 40.5 °C in 72 h-continuous cultures and decreased viabilities were also observed after 24–72 h at 40.5 °C. Flow cytometric analyses showed that the HeLa cells were arrested at G2/M after temperature shift-up to 40.5 °C. These physiological changes were potentiated in the presence of 3-aminobenzamide. Decrease in growth rates, increased cytotoxicity and G2/M arrest, were associated with the temperature-shift to 40.5 °C and are indirect evidence of DNA breaks. In addition to γH2AX, PAR could be a sensitive marker for DNA single- and double-strand breaks. These two molecular markers provide evidence of physiological changes occurring within cells. - Highlights: • Physiological level of poly(ADP-ribose) was determined during mild temperature shift. • Poly(ADP-ribose) level in HeLa and CHO-K1 cells significantly increased. • γH2AX signals increased during culture at 40.5 °C as compared to 37.0 °C. • Poly(ADP-ribose) polymerase inhibitor potentiated γH2AX signals at 40.5 °C. • γH2AX and poly(ADP-ribose) level provide evidence of physiological changes in cells.« less

First-principles Investigation of the Structure, Mobility and Optical Properties of Self-Trapped Excitons in Alkali Metal, Lanthanum and Barium Halide Scintillators

NASA Astrophysics Data System (ADS)

Bizarri, Gregory; Del Ben, Mauro; Bourret, Edith; Canning, Andrew

The performance of new and improved materials for gamma ray scintillator detectors is dependant on multiple factors such as quantum efficiency, energy transport etc. In halide scintillator materials the energy transport is often impacted by self-trapped exciton (STE) formation and mobility. We present first-principles calculations at the hybrid density functional theory level for the structure, mobility and optical properties of STEs and their associated lattice defects (VK centers) in two important families of scintillator materials, alkali metal and lanthanum halides (AX and LaX). AX and LaX have been extensively characterized by experiments and serve as benchmark systems to assess the accuracy of our theoretical procedure. We show that hydrid functionals accurately predict the different types of self-trapped excitons (on and off-center) found in AX and LX materials in agreement with EPR experiments. We then applied this approach to perform preliminary studies on classes of new scintillator materials including the barium mixed halides and compared with our new experimental results. These studies have the potential to benefit the development of improved scintillator materials tailored for specific applications. This work is supported by the U.S. Department of Energy/NNSA/DNN R&D and is carried out at Lawrence Berkeley National Laboratory under Contract No. AC02-05CH11231.

Tank 241-AX-104 upper vadose zone cone penetrometer demonstration sampling and analysis plan

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

FIELD, J.G.

1999-02-02

This sampling and analysis plan (SAP) is the primary document describing field and laboratory activities and requirements for the tank 241-AX-104 upper vadose zone cone penetrometer (CP) demonstration. It is written in accordance with Hanford Tank Initiative Tank 241-AX-104 Upper Vadose Zone Demonstration Data Quality Objective (Banning 1999). This technology demonstration, to be conducted at tank 241-AX-104, is being performed by the Hanford Tanks Initiative (HTI) Project as a part of Tank Waste Remediation System (TWRS) Retrieval Program (EM-30) and the Office of Science and Technology (EM-50) Tanks Focus Area. Sample results obtained as part of this demonstration will providemore » additional information for subsequent revisions to the Retrieval Performance Evaluation (RPE) report (Jacobs 1998). The RPE Report is the result of an evaluation of a single tank farm (AX Tank Farm) used as the basis for demonstrating a methodology for developing the data and analyses necessary to support making tank waste retrieval decisions within the context of tank farm closure requirements. The RPE includes a study of vadose zone contaminant transport mechanisms, including analysis of projected tank leak characteristics, hydrogeologic characteristics of tank farm soils, and the observed distribution of contaminants in the vadose zone in the tank farms. With limited characterization information available, large uncertainties exist as to the nature and extent of contaminants that may exist in the upper vadose zone in the AX Tank Farm. Traditionally, data has been collected from soils in the vadose zone through the installation of boreholes and wells. Soil samples are collected as the bore hole is advanced and samples are screened on site and/or sent to a laboratory for analysis. Some in-situ geophysical methods of contaminant analysis can be used to evaluate radionuclide levels in the soils adjacent to an existing borehole. However, geophysical methods require compensation for well casing interference and soil moisture content and may not be successful in some conditions. In some cases the level of interference must be estimated due to uncertainties regarding the materials used in well construction and soil conditions, Well casing deployment used for many in-situ geophysical methods is relatively expensive and geophysical methods do not generally provide real time values for contaminants. In addition, some of these methods are not practical within the boundaries of the tank farm due to physical constraints, such as underground piping and other hardware. The CP technologies could facilitate future characterization of vadose zone soils by providing vadose zone data in near real-time, reducing the number of soil samples and boreholes required, and reducing characterization costs.« less

Targeting the interleukin-23/17 axis in axial spondyloarthritis.

PubMed

Paine, Ananta; Ritchlin, Christopher T

2016-07-01

This article highlights and emphasizes how new knowledge of mechanisms linked to the interleukin-23 (IL-23)/IL-17 pathway is relevant to the pathophysiology of axial spondyloarthritis (axSpA) and demonstrates how molecules in IL-23/IL-17 pathway provide novel therapeutic targets for axSpA patients. Similarly to ankylosing spondylitis (AS), the increased frequency of Th17 cells in nr-axSpA patients underscores the concept that these disorders can be viewed on a spectrum. Recent findings suggest that the contribution of IL-23/IL-17 signaling pathways possibly differs in male and female AS patients. The finding that IL-17 and IL-22 secreting-type 3 innate lymphoid cells are increased in AS patients point to their potential role in the pathogenesis of axSpA. Reports of dysbiosis in the gut microbiome of AS patients support previous work indicating a possible causal relationship between altered gut flora, ileocolonic inflammation and axSpA. Of important clinical relevance are results from clinical trials supporting the efficacy and safety of agents that block IL-12/23 (ustekinumab) and IL-17 (secukinumab and ixekizumab) in AS patients. Recent studies further establish the central position of the IL-23/IL-17 pathway in the pathogenesis of axSpA. Targeting the IL-23/IL-17 pathway appears to be a safe and effective strategy for treatment of axSpA patients.

The performance of different classification criteria sets for spondyloarthritis in the worldwide ASAS-COMOSPA study.

PubMed

Bakker, Pauline; Moltó, Anna; Etcheto, Adrien; Van den Bosch, Filip; Landewé, Robert; van Gaalen, Floris; Dougados, Maxime; van der Heijde, Désirée

2017-05-16

In this study, we sought to compare the performance of spondyloarthritis (SpA) classification criteria sets in an international SpA cohort with patients included from five continents around the world. Data from the (ASAS) COMOrbidities in SPondyloArthritis (ASAS-COMOSPA) study were used. ASAS-COMOSPA is a multinational, cross-sectional study with consecutive patients diagnosed with SpA by rheumatologists worldwide. Patients were classified according to the European Spondyloarthropathy Study Group (ESSG), modified European Spondyloarthropathy Study Group (mESSG), Amor, modified Amor, Assessment of SpondyloArthritis international Society (ASAS) axial Spondyloarthritis (axSpA), ASAS peripheral spondyloarthritis (pSpA) and ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria. Overlap between the classification criteria sets was assessed for patients with and without back pain. Furthermore, patients fulfilling different arms of the ASAS axSpA criteria (imaging arm, clinical arm, both arms) were compared on the presence of SpA features. A total of 3942 patients (5 continents, 26 countries) were included. The mean age was 43.6 years, 65.0% were male, 56.2% were human leucocyte antigen B27-positive and 64.4% had radiographic sacroiliitis (based on modified New York criteria). Of the patients, 85.5% were classified by the ASAS SpA criteria (87.7% ASAS axSpA, 12.3% ASAS pSpA). Fulfilment of the Amor, ESSG and CASPAR criteria was present in 83.3%, 88.4% and 21.6% of patients, respectively. Of the patients with back pain (n = 3227), most were classified by all three of Amor, ESSG and ASAS axSpA criteria (71.4%). Patients fulfilling the imaging arm and the clinical arm of the ASAS axSpA criteria had similar presentations of SpA features. In patients without back pain, overlap between classification criteria sets was seen, although to a lesser extent. Most patients with a clinical diagnosis of axial SpA in the worldwide ASAS-COMOSPA study fulfil several classification criteria sets, and a substantial overlap between different criteria sets is seen, which suggests a high level of credibility of the criteria. Large inter-regional differences in the fulfilment of classification criteria were not found. Patients fulfilling the clinical arm were remarkably similar to patients fulfilling the imaging arm with respect to the presence of most SpA features.

Rheology and microstructure of gels based on wheat arabinoxylans enzymatically modified in arabinose and xylose

USDA-ARS?s Scientific Manuscript database

Atomic force microscopy (AFM) was used to investigate the microstructure of laccase-induced arabinoxylan (AX) gels for the first time. The effect of the degree of substitution (DS) of AX on gel microstructure was investigated by AFM. AX with three DS values (0.68, 0.61 and 0.51) were enzymatically t...

UV-induced replication arrest in the xeroderma pigmentosum variant leads to DNA double-strand breaks, γ-H2AX formation, and Mre11 relocalization

PubMed Central

Limoli, Charles L.; Giedzinski, Erich; Bonner, William M.; Cleaver, James E.

2002-01-01

UV-induced replication arrest in the xeroderma pigmentosum variant (XPV) but not in normal cells leads to an accumulation of the Mre11/Rad50/Nbs1 complex and phosphorylated histone H2AX (γ-H2AX) in large nuclear foci at sites of stalled replication forks. These complexes have been shown to signal the presence of DNA damage, in particular, double-strand breaks (DSBs). This finding suggests that UV damage leads to the formation of DSBs during the course of replication arrest. After UV irradiation, XPV cells showed a fluence-dependent increase in the yield of γ-H2AX foci that paralleled the production of Mre11 foci. The percentage of foci-positive cells increased rapidly (10–15%) up to fluences of 10 J⋅m−2 before saturating at higher fluences. Frequencies of γ-H2AX and Mre11 foci both reached maxima at 4 h after UV irradiation. This pattern contrasts sharply to the situation observed after x-irradiation, where peak levels of γ-H2AX foci were found to precede the formation of Mre11 foci by several hours. The nuclear distributions of γ-H2AX and Mre11 were found to colocalize spatially after UV- but not x-irradiation. UV-irradiated XPV cells showed a one-to-one correspondence between Mre11 and γ-H2AX foci-positive cells. These results show that XPV cells develop DNA DSBs during the course of UV-induced replication arrest. These UV-induced foci occur in cells that are unable to carry out efficient bypass replication of UV damage and may contribute to further genetic variation. PMID:11756691

Transgenic rice expressing the cry2AX1 gene confers resistance to multiple lepidopteran pests.

PubMed

Chakraborty, M; Reddy, P Sairam; Mustafa, G; Rajesh, G; Narasu, V M Laxmi; Udayasuriyan, V; Rana, Debashis

2016-10-01

A chimeric Bacillus thuringiensis toxin (Bt) gene, cry2AX1was cloned in a bi-selectable marker free binary vector construct. The cry2AX1 gene, driven by the Chrysanthemum rbcS1 promoter, was introduced into JK1044R, the restorer line (Oryza sativa L. ssp. Indica) of a notified commercially grown rice hybrid in India, by Agrobacterium-mediated transformation. Its effect against two major lepidopteran insect pests viz., yellow stem borer (YSB) Scirpophaga incertulas, rice leaf folder (RLF) Cnaphalocrocis medinalis and one minor insect pest, oriental army worm (OAW) Mythimna separata was demonstrated through bioassays of transgenic rice plants under laboratory and greenhouse conditions. The rbcS1 promoter with chloroplast signal peptide was used to avoid Cry2AX1 protein expression in rice seed endosperm tissue. A total of 37 independent transformants were generated, of which after preliminary molecular characterization and YSB bioassay screening, five events were selected for their protein expression and bioefficacy against all three rice insect. One elite transgenic rice line, BtE15, was identified with Cry2AX1 expression ranging from 0.68 to 1.34 µg g(-1) leaf fresh weight and with 80-92 % levels of resistance against rice pests at the vegetative and reproductive stages. Increase in Cry2AX1 protein concentration was also observed with crop maturity. The Cry2AX1protein concentration in the de-husked seeds was negligible (as low as 2.7-3.6 ng g(-1)). These results indicate the potential application of cry2AX1 gene in rice for protection against YSB, RLF and OAW.

A Micelle Self-Assembled from Doxorubicin-Arabinoxylan Conjugates with pH-Cleavable Bond for Synergistic Antitumor Therapy

NASA Astrophysics Data System (ADS)

Wang, Jie; Li, Yanli; Dong, Xia; Wang, Ying; Chong, Xiaodan; Yu, Tai; Zhang, Fulei; Chen, Di; Zhang, Li; Gao, Jie; Yang, Cheng; Han, Jun; Li, Wei

2017-01-01

Nanomedicine offers new hope to overcome the low solubility and high side toxicity to normal tissue appeared in traditional chemotherapy. The biocompatibility and intracellular drug accumulation is still a big challenge for the nano-based formulations. Herein, a medical-used biocompatible arabinoxylan (AX) is used to develop to delivery chemodrug doxorubicin (DOX). The solubility of DOX is obviously enhanced via the hydrogen bond formed with AX which results in an amphiphilic AX-DOX. A micelle with pH-cleavable bond is thus self-assembled from such AX-DOX with DOX core and AX shell. The inner DOX can be easily released out at low intracellular pH, which obviously enhanced its in vitro cytotoxicity against breast cancer cells (MCF-7). Interestingly, an unexpected apoptosis is evoked except for the proliferation inhibition. Moreover, the therapeutic effects are further synergistically promoted by the enhanced permeability and retention (EPR) and intracellular pH-triggered drug release. Consequently, the in vivo intratumor accumulation of DOX, the tumor inhibition was significantly promoted after intravenous administration to the Balb/c nude mice bearing MCF-7 tumors. These in vitro/vivo results indicated that the AX-DOX micellular formulation holds high potential in cancer therapy.

New advances in the understanding and treatment of axial spondyloarthritis: from chance to choice

PubMed Central

Dubash, Sayam; McGonagle, Dennis; Marzo-Ortega, Helena

2017-01-01

Axial spondyloarthritis (axSpA) is a chronic inflammatory condition that encompasses ankylosing spondylitis (AS) as well as non-radiographic axial disease (nr-axSpA) and can lead to chronic pain, structural damage and disability. The introduction of tumour necrosis factor inhibitor (TNFi) drugs for AS heralded a new era of drug therapeutics for what was previously a largely untreatable disease. This has now been expanded with the licensing of secukinumab, an interleukin 17A (IL-17A) inhibitor for the treatment of AS. Although biologic disease modifying antirheumatic drugs (bDMARDs) are not a first line treatment option in AS or axSpA, they are highly effective following incomplete or no response to physiotherapy and non-steroidal anti-inflammatory drugs (NSAIDs). Current research strategies aim to test whether the desired treatment goal of disease remission may now be achievable with early and stratified use of bDMARDs in both AS and nr-axSpA. This review summarizes the current literature on axSpA including pathophysiology, treatment indications, radiographic progression and the evidence for new developments in the treatment of both AS and nr-axSpA. PMID:29511503

Mean frequency and relative fluorescence intensity measurement of γ-H2AX foci dose response in PBL exposed to γ-irradiation: An inter- and intra-laboratory comparison and its relevance for radiation triage.

PubMed

Venkateswarlu, Raavi; Tamizh, Selvan G; Bhavani, Manivannan; Kumar, Arun; Alok, Amit; Karthik, Kanagaraj; Kalra, Namita; Vijayalakshmi, J; Paul, Solomon F D; Chaudhury, N K; Venkatachalam, Perumal

2015-12-01

Measurement of γ-H2AX protein changes in the peripheral blood lymphocytes (PBL) of individuals exposed to ionizing radiation is a simple, sensitive, and rapid assay for radiation triage and early marker of dose estimation. The qualitative and quantitative measurements of the protein changes were examined using flow cytometry and microscopy. Whole blood and isolated lymphocytes were exposed in vitro between 0.1 and 5 Gy doses of (60) Co γ-radiation at a dose rate of 1 Gy/min. Radiation induced γ-H2AX foci frequency (n = 3) and relative fluorescence intensity (n = 7) in PBL was measured at 0.5 and 2 hrs postexposure. The observed dose response for γ-H2AX foci frequency at both time points, for whole blood and isolated lymphocytes did not show any significant (P > 0.05) differences. However, when compared with γ-H2AX foci frequency scored manually (microscopy), the semiautomated analysis (captured images) showed a better correlation (r(2) = 0.918) than that obtained with automated (Metafer) scoring (r(2) = 0.690). It is noteworthy to mention that, the γ-H2AX foci frequency quantified using microscopy showed a dose dependent increase up to 2 Gy and the relative fluorescence intensity (RFI) measured with flow cytometry revealed an increase up to 5 Gy in the PBL exposed in vitro. Moreover, a better correlation was observed between the γ-H2AX foci frequency obtained by manual scoring and RFI (r(2) = 0.910). Kinetic studies showed that the γ-H2AX foci remain more or less unchanged up to 4 hrs and reduces gradually over 48 hrs of postexposure at 37°C. Further, inter and intra-laboratory comparisons showed consistency in the scoring of γ-H2AX foci frequency by manual and semiautomated scoring. The overall results suggest that measurement of γ-H2AX (microscopy and flow cytometry) should be employed within 4 to 6 hrs for a reliable dosimetry either by sharing the work load between the laboratories or investing more manpower; however, triage can be possible even up to 48 hrs of postirradiation. © 2015 International Society for Advancement of Cytometry.

MicroRNA-138 Regulates DNA Damage Response in Small Cell Lung Cancer Cells by Directly Targeting H2AX.

PubMed

Yang, Huan; Luo, Jinwen; Liu, Zhiguang; Zhou, Rui; Luo, Hong

2015-04-01

Lung cancer is the leading cause of cancer death worldwide and small cell lung cancer (SCLC) accounts for a significant proportion of all lung cancer cases. Even so, the underlying mechanism governing SCLC development remains poorly understood and SCLC related cancer death stands high despite decades of intensive investigation. We noted that both miR-138 and H2AX have been implicated in development of various malignancies. Also, there is a recent report showing the role of miR-138 in mediating DNA damage response by targeting H2AX. In light of these data, we sought to characterize the role of miR-138 for SCLC cell growth and cell-cycle progression by regulating H2AX expression. Results showed that miR-138 is significantly down-regulated in SCLC tumor tissues as well as in three SCLC cell lines. After successfully engineering miR-138 overexpression in one of the SCLC cell lines, NCI-H2081, we observed a remarkable reduction of cell growth and a significant inhibition on cell-cycle progression. Moreover, we were able to show that miR-138 potently inhibits H2AX expression, which suggests that H2AX may serve as a downstream executor for miR-138. Consistent with this hypothesis, we found that engineered H2AX knockdown achieves a similar effect as observed for miR-138 overexpression in terms of SCLC growth and cell cycle regulation. We also showed that H2AX overexpression largely abolished miR-138-mediated SCLC cancer cell growth and cell-cycle progression inhibition, which strongly suggests, at least in vitro, that miR-138 potently regulates SCLC development by targeting H2AX. In addition, we found lower miR-138 expression confers SCLC cells with greater DNA damage repair capacity. Finally, we were able to show miR-138 overexpression inhibits DNA damage repair in SCLC cells while miR-138 knockdown further facilitates DNA damage repair in these cells after IR. To date, there has been no study showing the role of miR-138/H2AX machinery in SCLC development. Our results may shed a light to development of new lines of SCLC diagnosis and treatment approaches.

Flares assessed weekly in patients with rheumatoid arthritis or axial spondyloarthritis and relationship with physical activity measured using a connected activity tracker: a 3-month study.

PubMed

Jacquemin, Charlotte; Molto, Anna; Servy, Hervé; Sellam, Jérémie; Foltz, Violaine; Gandjbakhch, Frédérique; Hudry, Christophe; Mitrovic, Stéphane; Granger, Benjamin; Fautrel, Bruno; Gossec, Laure

2017-01-01

The evolution of rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) is marked by flares, although their frequency is unclear. Flares may impact physical activity. Activity can be assessed objectively using activity trackers. The objective was to assess longitudinally the frequency of flares and the association between flares and objective physical activity. This prospective observational study (ActConnect) included patients with definite clinician-confirmed RA or axSpA, owning a smartphone. During 3 months, physical activity was assessed continuously by number of steps/day, using an activity tracker, and disease flares were self-assessed weekly using a specific flare question and, if relevant, the duration of the flare. The relationship between flares and physical activity for each week (time point) was assessed by linear mixed models. In all, 170/178 patients (91 patients with RA and 79 patients with axSpA; 1553 time points) were analysed: mean age was 45.5±12.4 years, mean disease duration was 10.3±8.7 years, 60 (35.3%) were men and 90 (52.9%) received biologics. The disease was well-controlled (mean Disease Activity Score 28: 2.3±1.2; mean Bath Ankylosing Spondylitis Disease Activity Index score: 3.3±2.1). Patients self-reported flares in 28.2%±28.1% of the weekly assessments. Most flares (78.9%±31.4%) lasted ≤3 days. Persistent flares lasting more than 3 days were independently associated with less weekly physical activity (p=0.03), leading to a relative decrease of 12%-21% and an absolute decrease ranging from 836 to 1462 steps/day. Flares were frequent but usually of short duration in these stable patients with RA and axSpA. Persistent flares were related to a moderate decrease in physical activity, confirming objectively the functional impact of patient-reported flares.

Flares assessed weekly in patients with rheumatoid arthritis or axial spondyloarthritis and relationship with physical activity measured using a connected activity tracker: a 3-month study

PubMed Central

Jacquemin, Charlotte; Molto, Anna; Servy, Hervé; Sellam, Jérémie; Foltz, Violaine; Gandjbakhch, Frédérique; Hudry, Christophe; Mitrovic, Stéphane; Granger, Benjamin; Fautrel, Bruno; Gossec, Laure

2017-01-01

Background The evolution of rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) is marked by flares, although their frequency is unclear. Flares may impact physical activity. Activity can be assessed objectively using activity trackers. The objective was to assess longitudinally the frequency of flares and the association between flares and objective physical activity. Methods This prospective observational study (ActConnect) included patients with definite clinician-confirmed RA or axSpA, owning a smartphone. During 3 months, physical activity was assessed continuously by number of steps/day, using an activity tracker, and disease flares were self-assessed weekly using a specific flare question and, if relevant, the duration of the flare. The relationship between flares and physical activity for each week (time point) was assessed by linear mixed models. Results In all, 170/178 patients (91 patients with RA and 79 patients with axSpA; 1553 time points) were analysed: mean age was 45.5±12.4 years, mean disease duration was 10.3±8.7 years, 60 (35.3%) were men and 90 (52.9%) received biologics. The disease was well-controlled (mean Disease Activity Score 28: 2.3±1.2; mean Bath Ankylosing Spondylitis Disease Activity Index score: 3.3±2.1). Patients self-reported flares in 28.2%±28.1% of the weekly assessments. Most flares (78.9%±31.4%) lasted ≤3 days. Persistent flares lasting more than 3 days were independently associated with less weekly physical activity (p=0.03), leading to a relative decrease of 12%–21% and an absolute decrease ranging from 836 to 1462 steps/day. Conclusion Flares were frequent but usually of short duration in these stable patients with RA and axSpA. Persistent flares were related to a moderate decrease in physical activity, confirming objectively the functional impact of patient-reported flares. PMID:28879046

The Weaponization Of Migration: Examining Migration As a 21st Century Tool Of Political Warfare

DTIC Science & Technology

2017-12-01

em ittan ces / D iasp o ra T ax Pre...YEAR CHALLENGER ASSISTED BY TARGET LOCATION M ig ran ts U sed fo r M an p o w er In filtratio n D isru p t / D ep riv e E n em y...counterinsurgency move. In Syria, indiscriminate bombing by Russian and Syrian forces continues to cause significant population displacement

Nonlinear Oscillations of a Fluttering Panel in a Transonic Airstream.

DTIC Science & Technology

1983-04-01

u-+ . w 2 (b) I2u + 2v + iw w - 2aw ( xy 3+ax ax ay ax3y where z is measured from the midsurface of the panel. Equation I3 (1) is a modification of a...small deflection theory to include the first order effects of midsurface stretching necessary to inves- I tigate large deflections. Now Hamilton’s

Relationship Between Psychiatric Status, Self-Reported Outcome Measures, and Clinical Parameters in Axial Spondyloarthritis

PubMed Central

Kilic, Gamze; Kilic, Erkan; Ozgocmen, Salih

2014-01-01

Abstract This article aims to compare the risks of depression and anxiety in patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA) and investigate the relationship among self-reported outcome measures, clinical parameters, and physical variables of patients with axSpA. Patients with axSpA were recruited from Erciyes Spondyloarthritis Cohort. The patients met Assessment of Spondyloarthritis International Society classification criteria for axial SpA and were assessed in a cross-sectional study design for visual analog scale (VAS) pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Quality of Life questionnaire (ASQoL), and Ankylosing Spondylitis Disease Activity Score–C-reactive protein (ASDAS-CRP). Psychological status was evaluated using the hospital anxiety and depression scale (HADS). Multivariate logistic regression analysis was applied to determine the associations between psychological variables and clinical parameters after adjusting for confounding variables. Of the 316 patients (142 nr-axSpA, 174 AS), 139 (44%) had high risk for depression (HADS-D score ≥7) and 71 (22.5%) for anxiety (HADS-A score ≥10). HADS-D and HADS-A scores were similar between patients with AS and nr-axSpA. Patients with high risk for depression and anxiety had higher scores in BASDAI, BASFI, and ASDAS-CRP, and also poorer scores in VAS pain and ASQoL. Multivariate logistic regression analysis showed that the ASDAS-CRP, ASQoL, BASDAI, as well as educational level were factors associated with the risk of depression whereas the ASQoL and educational level were factors associated with the risk of anxiety. Patients with nr-axSpA and AS have similar burden of psychological distress. The quality of life (ASQoL) and educational level were factors associated with the risk of both depression and anxiety whereas disease activity (BASDAI and ASDAS-CRP) was the independent risk factor associated with depression but not anxiety in axSpA. These findings suggest that psychological status should be examined while assessing patients with axSpA including AS and nr-axSpA. PMID:25546683

Effect of dietary formic acid and astaxanthin on the survival and growth of Pacific white shrimp (Litopenaeus vannamei) and their resistance to Vibrio parahaemolyticus.

PubMed

Chuchird, Niti; Rorkwiree, Phitsanu; Rairat, Tirawat

2015-01-01

A 90-day feeding trial was conducted to evaluate the effects of formic acid (FA) and astaxanthin (AX) on growth, survival, immune parameters, and tolerance to Vibrio infection in Pacific white shrimp. The study was divided into two experiments. In experiment 1, postlarvae-12 were randomly distributed into six groups and then fed four times daily with six experimental diets contained 0.3 % FA, 0.6 % FA, 50 ppm AX, 0.3 % FA + 50 ppm AX, 0.6 % FA + 50 ppm AX, or none of these supplements (control diet). After 60 days of the feeding trials, the body weight of all treatment groups was not significantly different from the control group, although shrimp fed formic acid had significantly lower body weight than shrimp fed 50 ppm AX. However, the 0.6 % FA + 50 ppm AX group had a significantly higher survival rate (82.33 ± 8.32 %) than the control group (64.33 ± 10.12 %). In experiment 2, Vibrio parahaemolyticus was added to each tank to obtain a final concentration of 10(4) colony-forming units/mL. Each treatment group received the aforementioned diets for another 30 days. At the end of this experiment, there was no difference in the weight gain among all experimental groups. However, the survival rate of shrimps whose diet included FA, AX, and their combination (in the range of 45.83-67.50 %) was significantly higher than the control group (20.00 ± 17.32 %). FA-fed shrimps also had significantly lower total intestinal bacteria and Vibrio spp. counts, while immune parameters [total hemocyte count (THC), phagocytosis activity, phenoloxidase (PO) activity, and superoxide dismutase (SOD) activity] of AX-fed groups were significantly improved compared with the other groups. In conclusion, FA, AX, and their combination are useful in shrimp aquaculture.

Multiple rare-earth ion environments in amorphous (Gd2O3 ) 0.230(P2O5) 0.770 revealed by gadolinium K -edge anomalous x-ray scattering

NASA Astrophysics Data System (ADS)

Cole, Jacqueline M.; Cramer, Alisha J.; Shastri, Sarvjit D.; Mukaddem, Karim T.; Newport, Robert J.

2018-04-01

A Gd K -edge anomalous x-ray scattering (AXS) study is performed on the rare-earth (R ) phosphate glass, (Gd2O3 ) 0.230(P2O5) 0.770 , in order to determine Gd ⋯Gd separations in its local structure. The minimum rare-earth separation is of particular interest given that the optical properties of these glasses can quench when rare-earth ions become too close to each other. To this end, a weak Gd ⋯Gd pairwise correlation is located at 4.2 (1 )Å , which is representative of a metaphosphate R ⋯R separation. More intense first-neighbor Gd ⋯Gd pairwise correlations are found at the larger radial distributions, 4.8(1), 5.1(1), and 5.4 (1 )Å . These reflect a mixed ultraphosphate and metaphosphate structural character, respectively. A second-neighbor Gd ⋯Gd pairwise correlation lies at 6.6 (1 )Å which is indicative of metaphosphate structures. Meta- and ultraphosphate classifications are made by comparing the R ⋯R separations against those of rare-earth phosphate crystal structures, R (PO3) 3 and R P5O14 , respectively, or difference pair-distribution function (Δ PDF ) features determined on similar glasses using difference neutron-scattering methods. The local structure of this glass is therefore found to display multiple rare-earth ion environments, presumably because its composition lies between these two stoichiometric formulae. These Gd ⋯Gd separations are well-resolved in Δ PDFs that represent the AXS signal. Indeed, the spatial resolution is so good that it also enables the identification of R ⋯X (X =R , P, O) pairwise correlations up to r ˜9 Å ; their average separations lie at r ˜7.1 (1 ) , 7.6(1), 7.9(1), 8.4(1), and 8.7 (1 )Å . This is a report of a Gd K -edge AXS study on an amorphous material. Its demonstrated ability to characterize the local structure of a glass up to such a long range of r heralds exciting prospects for AXS studies on other ternary noncrystalline materials. However, the technical challenge of such an experiment should not be underestimated, as is highlighted in this work where probing AXS signal near the Gd K edge is found to produce inelastic x-ray scattering that precludes the normal AXS methods of data processing. Nonetheless, it is shown that AXS results are not only tractable but they also reveal local structure of rare-earth phosphate glasses that is important from a materials-centered perspective and which could not be obtained by other materials characterization methods.

Multiple rare-earth ion environments in amorphous ( G d 2 O 3 ) 0.230 ( P 2 O 5 ) 0.770 revealed by gadolinium K -edge anomalous x-ray scattering

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

Cole, Jacqueline M.; Cramer, Alisha J.; Shastri, Sarvjit D.

A Gd K-edge anomalous X-ray scattering (AXS) study is performed on the rare-earth (R) phosphate glass, (Gd2O3)0.230(P2O5)0.770, in order to determine Gd…Gd separations in its local structure. The minimum rare-earth separation is of particular interest given that the optical properties of these glasses can quench when rare-earth ions become too close to each other. To this end, a weak Gd…Gd pairwise correlation is located at 4.2(1) Å which is representative of a meta-phosphate R…R separation. More intense first neighbor Gd…Gd pairwise correlations are found at the larger radial distributions, 4.8(1) Å, 5.1(1) Å and 5.4(1) Å. These reflect a mixedmore » ultra-phosphate and meta-phosphate structural character, respectively. A second neighbor Gd…Gd pairwise correlation lies at 6.6(1) Å which is indicative of meta-phosphate structures. Meta- and ultra-phosphate classifications are made by comparing the R…R separations against those of rare-earth phosphate crystal structures, R(PO3)3 and RP5O14 respectively, or difference pair distribution function (ΔPDF) features determined on similar glasses using difference neutron scattering methods. The local structure of this glass is therefore found to display multiple rare-earth ion environments, presumably because its composition lies between these two stoichiometric formulae. These Gd…Gd separations are well resolved in the ΔPDFs that represent the AXS signal. Indeed, the spatial resolution is so good that it also enables the identification of R…X (X = R, P, O) pairwise correlations up to r ~ 9 Å; their average separations lie at r ~ 7.1(1) Å, 7.6(1) Å 7.9(1) Å, 8.4(1) Å and 8.7(1) Å. This is the first report of a Gd K-edge AXS study on an amorphous material. Its demonstrated ability to characterize the local structure of a glass up to such a long-range of r, heralds exciting prospects for AXS studies on other ternary non-crystalline materials. However, the technical challenge of such an experiment should not be underestimated, as is highlighted in this work where probing AXS signal near the Gd K-edge is found to produce inelastic X-ray scattering that precludes the normal AXS methods of data processing. Nonetheless, it is shown that AXS results are not only tractable but they also reveal local structure of rare-earth phosphate glasses that is important from a materials-centered perspective and which could not be obtained by other materials characterization methods.« less

Inflammatory back pain in psoriatic arthritis is significantly more responsive to corticosteroids compared to back pain in ankylosing spondylitis: a prospective, open-labelled, controlled pilot study.

PubMed

Haroon, Muhammad; Ahmad, Muddassar; Baig, Muhammad Nouman; Mason, Olivia; Rice, John; FitzGerald, Oliver

2018-04-17

The efficacy of corticosteroids in patients with psoriatic arthritis (PsA) and inflammatory back pain has not been studied to date. In this controlled trial, we aimed to investigate the comparative performance of corticosteroids in patients with active axial-PsA (AxPsA) versus those with active ankylosing spondylitis (AS). Patients with AxPsA and AS (naïve to biologic therapies), who not only had clinically active disease, but also had bone marrow oedema on magnetic resonance imaging of the sacroiliac joints, were recruited. Clinically active disease was defined as inflammatory back pain (fulfilling Assessment of Spondyloarthritis International Society (ASAS) expert criteria), with spinal pain score (numerical rating scale 0-10) ≥4 and Bath AS Disease Activity Index (BASDAI) score ≥4 despite taking nonsteroidal anti-inflammatory drugs. Moreover, we recruited a control group of patients with non-inflammatory lower back pain. All patients received a single, intra-muscular dose of depot corticosteroid injection (triamcinolone acetonide 80 mg) at baseline. The intra-muscular corticosteroid option was used to overcome any drug compliance issues. Clinical outcome assessments were made at the following time points: baseline, week 2, and week 4. The primary efficacy end point was mean change in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 2. Key secondary outcomes were mean change in the BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI) and Ankylosing Spondylitis Quality of Life (ASQoL) at weeks 2 and 4. In total, 40 patients were recruited (15 with AxPsA, 15 with AS, and 10 controls). At week 2 following corticosteroid treatment, patients with AxPsA had significantly greater improvement in the mean ASDAS compared to patients with AS (1.43 ± 0.39 vs. 1.03 ± 0.30, p = 0.004), and also when compared to controls (p < 0.001). At week-4, similar significant trend of ASDAS improvement was seen among AxPsA patients compared to AS patients (1.09 ± 0.32 vs. 0.77 ± 0.27, p = 0.007) and controls (p < 0.001). Similarly, the mean BASDAI, visual analogue scale spinal pain score, ASQoL and BASFI improved significantly among patients with AxPsA compared to patients with AS and controls at week 2 (p < 0.05), with this trend also largely maintained at week 4. Axial inflammation in patients with PsA responds significantly better to corticosteroids than in patients with AS. This furthers the argument and adds to the growing evidence that AxPsA and AS are distinct entities.

Glutathione S-transferase 4 is a putative DIF-binding protein that regulates the size of fruiting bodies in Dictyostelium discoideum.

PubMed

Kuwayama, Hidekazu; Kikuchi, Haruhisa; Oshima, Yoshiteru; Kubohara, Yuzuru

2016-12-01

In the development of the cellular slime mold Dictyostelium discoideum , two chlorinated compounds, the differentiation-inducing factors DIF-1 and DIF-2, play important roles in the regulation of both cell differentiation and chemotactic cell movement. However, the receptors of DIFs and the components of DIF signaling systems have not previously been elucidated. To identify the receptors for DIF-1 and DIF-2, we here performed DIF-conjugated affinity gel chromatography and liquid chromatography-tandem mass spectrometry and identified the glutathione S-transferase GST4 as a major DIF-binding protein. Knockout and overexpression mutants of gst4 ( gst4 - and gst4 OE , respectively) formed fruiting bodies, but the fruiting bodies of gst4 - cells were smaller than those of wild-type Ax2 cells, and those of gst4 OE cells were larger than those of Ax2 cells. Both chemotaxis regulation and in vitro stalk cell formation by DIFs in the gst4 mutants were similar to those of Ax2 cells. These results suggest that GST4 is a DIF-binding protein that regulates the sizes of cell aggregates and fruiting bodies in D. discoideum .

Evaluation of the efficacy of radiation-modifying compounds using γH2AX as a molecular marker of DNA double-strand breaks.

PubMed

Mah, Li-Jeen; Orlowski, Christian; Ververis, Katherine; Vasireddy, Raja S; El-Osta, Assam; Karagiannis, Tom C

2011-01-25

Radiation therapy is a widely used therapeutic approach for cancer. To improve the efficacy of radiotherapy there is an intense interest in combining this modality with two broad classes of compounds, radiosensitizers and radioprotectors. These either enhance tumour-killing efficacy or mitigate damage to surrounding non-malignant tissue, respectively. Radiation exposure often results in the formation of DNA double-strand breaks, which are marked by the induction of H2AX phosphorylation to generate γH2AX. In addition to its essential role in DDR signalling and coordination of double-strand break repair, the ability to visualize and quantitate γH2AX foci using immunofluorescence microscopy techniques enables it to be exploited as an indicator of therapeutic efficacy in a range of cell types and tissues. This review will explore the emerging applicability of γH2AX as a marker for monitoring the effectiveness of radiation-modifying compounds.

Evaluation of the efficacy of radiation-modifying compounds using γH2AX as a molecular marker of DNA double-strand breaks

PubMed Central

2011-01-01

Radiation therapy is a widely used therapeutic approach for cancer. To improve the efficacy of radiotherapy there is an intense interest in combining this modality with two broad classes of compounds, radiosensitizers and radioprotectors. These either enhance tumour-killing efficacy or mitigate damage to surrounding non-malignant tissue, respectively. Radiation exposure often results in the formation of DNA double-strand breaks, which are marked by the induction of H2AX phosphorylation to generate γH2AX. In addition to its essential role in DDR signalling and coordination of double-strand break repair, the ability to visualize and quantitate γH2AX foci using immunofluorescence microscopy techniques enables it to be exploited as an indicator of therapeutic efficacy in a range of cell types and tissues. This review will explore the emerging applicability of γH2AX as a marker for monitoring the effectiveness of radiation-modifying compounds. PMID:21261999

Establishment of a γ-H2AX foci-based assay to determine biological dose of radon to red bone marrow in rats

PubMed Central

Wang, Jing; He, Linfeng; Fan, Dunhuang; Ding, Defang; Wang, Xufei; Gao, Yun; Zhang, Xuxia; Li, Qiang; Chen, Honghong

2016-01-01

The biodosimetric information is critical for assessment of cancer risk in populations exposed to high radon. However, no tools are available for biological dose estimation following radon exposure. Here, we established a γ-H2AX foci-based assay to determine biological dose to red bone marrow (RBM) in radon-inhaled rats. After 1–3 h of in vitro radon exposure, a specific pattern of γ-H2AX foci, linear tracks with individual p-ATM and p-DNA-PKcs foci, was observed, and the yield of γ-H2AX foci and its linear tracks displayed a linear dose-response manner in both rat peripheral blood lymphocytes (PBLs) and bone-marrow lymphocytes (BMLs). When the cumulative doses of radon inhaled by rats reached 14, 30 and 60 working level months (WLM), the yields of three types of foci markedly increased in both PBLs and BMLs, and γ-H2AX foci-based dose estimates to RBM were 0.97, 2.06 and 3.94 mGy, respectively. Notably, BMLs displayed a more profound increase of three types of foci than PBLs, and the absorbed dose ratio between BMLs and PBLs was similar between rats exposed to 30 and 60 WLM of radon. Taken together, γ-H2AX foci quantitation in PBLs is able to estimate RBM-absorbed doses with the dose-response curve of γ-H2AX foci after in vitro radon exposure and the ratio of RBM- to PBL-absorbed doses in rats following radon exposure. PMID:27445126

Influence of Different Antioxidants on X-Ray Induced DNA Double-Strand Breaks (DSBs) Using γ-H2AX Immunofluorescence Microscopy in a Preliminary Study

PubMed Central

Brand, Michael; Sommer, Matthias; Ellmann, Stephan; Wuest, Wolfgang; May, Matthias S.; Eller, Achim; Vogt, Sabine; Lell, Michael M.; Kuefner, Michael A.; Uder, Michael

2015-01-01

Background Radiation exposure occurs in X-ray guided interventional procedures or computed tomography (CT) and γ-H2AX-foci are recognized to represent DNA double-strand breaks (DSBs) as a biomarker for radiation induced damage. Antioxidants may reduce the induction of γ-H2AX-foci by binding free radicals. The aim of this study was to establish a dose-effect relationship and a time-effect relationship for the individual antioxidants on DSBs in human blood lymphocytes. Materials and Methods Blood samples from volunteers were irradiated with 10 mGy before and after pre-incubation with different antioxidants (zinc, trolox, lipoic acid, ß-carotene, selenium, vitamin E, vitamin C, N-acetyl-L-cysteine (NAC) and Q 10). Thereby, different pre-incubation times, concentrations and combinations of drugs were evaluated. For assessment of DSBs, lymphocytes were stained against the phosphorylated histone variant γ-H2AX. Results For zinc, trolox and lipoic acid regardless of concentration or pre-incubation time, no significant decrease of γ-H2AX-foci was found. However, ß-carotene (15%), selenium (14%), vitamin E (12%), vitamin C (25%), NAC (43%) and Q 10 (18%) led to a significant reduction of γ-H2AX-foci at a pre-incubation time of 1 hour. The combination of different antioxidants did not have an additive effect. Conclusion Antioxidants administered prior to irradiation demonstrated the potential to reduce γ-H2AX-foci in blood lymphocytes. PMID:25996998

Establishment of a γ-H2AX foci-based assay to determine biological dose of radon to red bone marrow in rats

NASA Astrophysics Data System (ADS)

Wang, Jing; He, Linfeng; Fan, Dunhuang; Ding, Defang; Wang, Xufei; Gao, Yun; Zhang, Xuxia; Li, Qiang; Chen, Honghong

2016-07-01

The biodosimetric information is critical for assessment of cancer risk in populations exposed to high radon. However, no tools are available for biological dose estimation following radon exposure. Here, we established a γ-H2AX foci-based assay to determine biological dose to red bone marrow (RBM) in radon-inhaled rats. After 1-3 h of in vitro radon exposure, a specific pattern of γ-H2AX foci, linear tracks with individual p-ATM and p-DNA-PKcs foci, was observed, and the yield of γ-H2AX foci and its linear tracks displayed a linear dose-response manner in both rat peripheral blood lymphocytes (PBLs) and bone-marrow lymphocytes (BMLs). When the cumulative doses of radon inhaled by rats reached 14, 30 and 60 working level months (WLM), the yields of three types of foci markedly increased in both PBLs and BMLs, and γ-H2AX foci-based dose estimates to RBM were 0.97, 2.06 and 3.94 mGy, respectively. Notably, BMLs displayed a more profound increase of three types of foci than PBLs, and the absorbed dose ratio between BMLs and PBLs was similar between rats exposed to 30 and 60 WLM of radon. Taken together, γ-H2AX foci quantitation in PBLs is able to estimate RBM-absorbed doses with the dose-response curve of γ-H2AX foci after in vitro radon exposure and the ratio of RBM- to PBL-absorbed doses in rats following radon exposure.

Prevalence of HLA-B27 in the general population and in patients with axial spondyloarthritis in Saudi Arabia.

PubMed

Omair, Mohammed A; AlDuraibi, Fatmah K; Bedaiwi, Mohammed K; Abdulaziz, Sultana; Husain, Waleed; El Dessougi, Maha; Alhumaidan, Hind; Al Khabbaz, Hana J; Alahmadi, Ibrahim; Omair, Maha A; Al Saleh, Salman; Alismael, Khalid; Al Awwami, Moheeb

2017-07-01

The prevalence of HLA-B27 in the general population and in axial spondyloarthritis (axSpA) patients in Saudi Arabia is unknown. The aim of this study was to evaluate the prevalence of HLA-B27 in these two populations and describe the delay in diagnosis of axSpA patients. The prevalence of HLA-B27 in the general population was evaluated using cord blood and healthy organ transplant donor databases. Data from patients with axSpA were collected retrospectively from five centers. Ankylosing spondylitis (AS) was diagnosed based on a positive X-ray, as evaluated by two independent readers. Patients with inflammatory bowel disease and psoriasis were excluded. A total of 134 axSpA patients were included, of whom 107 (79.9%) had AS, and most (67.2%) were males. HLA-B27 was positive in 60.4, 69, and 25.9% of patients with axSpA, AS, and non-radiographic axSpA (nr-axSpA), respectively. The median and interquartile range (IQR) ages at symptom onset and disease diagnosis were 26 (20-33) and 30 (25-38) years, respectively. The median delay to diagnosis was 3 (1-6) years. There was a negative correlation between the time of onset of symptoms and the delay in diagnosis (r = -0.587). Male gender and HLA-B27 positivity were associated with a younger age at symptom onset/diagnosis (p < 0.05). HLA-B27 was positive in 82/3332 (2.5%) and 27/1164 (2.3%) individuals in the cord blood and healthy organ transplant donor databases, respectively. The prevalence of HLA-B27 is lower in the general Saudi population and in axSpA patients compared to Caucasians, thus, limiting its utility as a diagnostic criterion.

Fiber and nonstarch polysaccharide content and variation in common crops used in broiler diets.

PubMed

Knudsen, Knud Erik Bach

2014-09-01

The current paper reviews content and variation in fiber and nonstarch polysaccharides (NSP) of common crops used in broiler diets. The cereal grain is a complex structure, and its cell walls (CW) differ in their composition and hence properties. Arabinoxylan (AX), mixed linkage (1→3; 1→4)-β-glucan (β-glucan), cellulose, and the noncarbohydrate component lignin are the predominant polymers in cereals. They occur in different proportions depending on the species and tissue type. Rye, triticale, wheat, corn, and sorghum are all rich in AX, whereas barley and oats contain a high level of β-glucan. The AX from rye, wheat, and triticale and β-glucan from barley and oats are to a large extent soluble, whereas the solubility of AX found in corn and sorghum is lower than the other cereals. The ratio of arabinose to xylose gives a crude indication of the AX structure, which varies between the endosperm, the aleurone and the outer grain layers as well as between the same tissues from different grains. Varietal differences in AX structure of the endosperm are also identified. From the analysis of the released oligomers after hydrolysis with a specific (1→3,1→4)-β-d-glucan hydrolase, it is found that the ratio of trisaccharides (degree of polymerization 3) and tetrasaccharides (degree of polymerization 4) varies depending on the source, being higher in barley than in oats but lower than in wheat. The molecular weight of β-glucan is higher than that of AX, and both polymers contribute to the viscosity of the extract. However, because AX molecules are more resistant to degradation than β-glucan, the use of AX rich grains in broiler diets is usually more problematic than those containing high concentrations of β-glucan. The cereal coproducts (brans and hulls) are concentrated sources of cellulose, lignin, and insoluble AX, but β-glucan can also be present mainly in rye and wheat brans. The CW composition of seeds and grains of protein crops and feedstuffs are different from that of cereals. The main CW polymers are pectic substances (homogalacturonan, rhamnogalacturonan type I and II, xylogalacturonan, and arabinogalactans type I and II), xyloglucans, and cellulose, but there are significant differences in the composition of the parenchymatous (cotyledon) tissues and that of the hulls. In the hulls, cellulose is the predominant polysaccharide, followed by acidic xylans and pectic substances. The implications of the heterogeneous CW for the action of exogenous enzymes are discussed. © 2014 Poultry Science Association Inc.

Diffusion-weighted Imaging Is a Sensitive and Specific Magnetic Resonance Sequence in the Diagnosis of Ankylosing Spondylitis.

PubMed

Bradbury, Linda A; Hollis, Kelly A; Gautier, Benoît; Shankaranarayana, Sateesh; Robinson, Philip C; Saad, Nivene; Lê Cao, Kim-Anh; Brown, Matthew A

2018-06-01

We tested the discriminatory capacity of diffusion-weighted magnetic resonance imaging (DWI) and its potential as an objective measure of treatment response to tumor necrosis factor inhibition in ankylosing spondylitis (AS). Three cohorts were studied prospectively: (1) 18 AS patients with Bath Ankylosing Spondylitis Disease Activity Index > 4, and erythrocyte sedimentation rate > 25 and/or C-reactive protein > 10 meeting the modified New York criteria for AS; (2) 20 cases of nonradiographic axial spondyloarthritis (nr-axSpA) as defined by the Assessment of Spondyloarthritis international Society (ASAS) criteria; and (3) 20 non-AS patients with chronic low back pain, aged between 18 and 45 years, who did not meet the imaging arm of the ASAS criteria for axSpA. Group 1 patients were studied prior to and following adalimumab treatment. Patients were assessed by DWI and conventional magnetic resonance imaging (MRI), and standard nonimaging measures. At baseline, in contrast to standard nonimaging measures, DWI apparent diffusion coefficient (ADC) values showed good discriminatory performance [area under the curve (AUC) > 80% for Group 1 or 2 compared with Group 3]. DWI ADC values were significantly lower posttreatment (0.45 ± 0.433 before, 0.154 ± 0.23 after, p = 0.0017), but had modest discriminating capacity comparing pre- and posttreatment measures (AUC = 68%). This performance was similar to the manual Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. DWI is informative for diagnosis of AS and nr-axSpA, and has moderate utility in assessment of disease activity or treatment response, with performance similar to that of the SPARCC MRI score.

γ-H2AX/53BP1/pKAP-1 foci and their linear tracks induced by in vitro exposure to radon and its progeny in human peripheral blood lymphocytes

PubMed Central

Ding, Defang; Zhang, Yaping; Wang, Jing; Wang, Xufei; Fan, Dunhuang; He, Linfeng; Zhang, Xuxia; Gao, Yun; Li, Qiang; Chen, Honghong

2016-01-01

The biodosimetric information is critical for evaluating the human health hazards caused by radon and its progeny. Here, we demonstrated that the formation of phosphorylated histone variant H2AX (γ-H2AX), p53-binding protein 1 (53BP1) and phosphorylated KRAB-associated protein 1 (pKAP-1) foci and their linear tracks in human peripheral blood lymphocytes (HPBLs) in vitro exposed to radon and its progeny were dependent on the cumulative absorbed dose of radon exposure but was unrelated to the concentration of radon. Among them, γ-H2AX foci and its linear tracks were the most sensitive indicators with the lowest estimable cumulative absorbed dose of 1.74 mGy from their linear dose-response curves and sustained for 12 h after termination of radon exposure. In addition, three types of foci showed an overdispersed non-Poisson distribution in HPBLs. The ratios of pKAP-1/γ-H2AX foci co-localization, 53BP1/γ-H2AX foci co-localization and 53BP1/pKAP-1 foci co-localization were significantly increased in HPBLs exposed to radon while they were unrelated to the cumulative dose of radon exposure, suggesting that γ-H2AX, pKAP-1 and 53BP1 play an important role in the repair of heterochromatic double-strand breaks. Altogether, our findings provide an experimental basis for estimating the biological dose of internal α-particle irradiation from radon and its progeny exposure in humans. PMID:27922110

γ-H2AX as a Marker for Dose Deposition in the Brain of Wistar Rats after Synchrotron Microbeam Radiation

PubMed Central

Fernandez-Palomo, Cristian; Mothersill, Carmel; Bräuer-Krisch, Elke; Laissue, Jean; Seymour, Colin; Schültke, Elisabeth

2015-01-01

Objective Synchrotron radiation has shown high therapeutic potential in small animal models of malignant brain tumours. However, more studies are needed to understand the radiobiological effects caused by the delivery of high doses of spatially fractionated x-rays in tissue. The purpose of this study was to explore the use of the γ-H2AX antibody as a marker for dose deposition in the brain of rats after synchrotron microbeam radiation therapy (MRT). Methods Normal and tumour-bearing Wistar rats were exposed to 35, 70 or 350 Gy of MRT to their right cerebral hemisphere. The brains were extracted either at 4 or 8 hours after irradiation and immediately placed in formalin. Sections of paraffin-embedded tissue were incubated with anti γ-H2AX primary antibody. Results While the presence of the C6 glioma does not seem to modulate the formation of γ-H2AX in normal tissue, the irradiation dose and the recovery versus time are the most important factors affecting the development of γ-H2AX foci. Our results also suggest that doses of 350 Gy can trigger the release of bystander signals that significantly amplify the DNA damage caused by radiation and that the γ-H2AX biomarker does not only represent DNA damage produced by radiation, but also damage caused by bystander effects. Conclusion In conclusion, we suggest that the γ-H2AX foci should be used as biomarker for targeted and non-targeted DNA damage after synchrotron radiation rather than a tool to measure the actual physical doses. PMID:25799425

Explanation for excessive DNA single-strand breaks and endogenous repair foci in pluripotent mouse embryonic stem cells.

PubMed

Banáth, J P; Bañuelos, C A; Klokov, D; MacPhail, S M; Lansdorp, P M; Olive, P L

2009-05-01

Pluripotent mouse embryonic stem cells (mES cells) exhibit approximately 100 large gammaH2AX repair foci in the absence of measurable numbers of DNA double-strand breaks. Many of these cells also show excessive numbers of DNA single-strand breaks (>10,000 per cell) when analyzed using the alkaline comet assay. To understand the reasons for these unexpected observations, various methods for detecting DNA strand breaks were applied to wild-type mES cells and to mES cells lacking H2AX, ATM, or DNA-PKcs. H2AX phosphorylation and expression of other repair complexes were measured using flow and image analysis of antibody-stained cells. Results indicate that high numbers of endogenous gammaH2AX foci and single-strand breaks in pluripotent mES cells do not require ATM or DNA-PK kinase activity and appear to be associated with global chromatin decondensation rather than pre-existing DNA damage. This will limit applications of gammaH2AX foci analysis in mES cells to relatively high levels of initial or residual DNA damage. Excessive numbers of single-strand breaks in the alkaline comet assay can be explained by the vulnerability of replicating chromatin in mES cells to osmotic shock. This suggests that caution is needed in interpreting results with the alkaline comet assay when applied to certain cell types or after treatment with agents that make chromatin vulnerable to osmotic changes. Differentiation of mES cells caused a reduction in histone acetylation, gammaH2AX foci intensity, and DNA single-strand breakage, providing a link between chromatin structural organization, excessive gammaH2AX foci, and sensitivity of replicating mES cell chromatin to osmotic shock.

Relationship between DNA damage response, initiated by camptothecin or oxidative stress, and DNA replication, analyzed by quantitative 3D image analysis.

PubMed

Berniak, K; Rybak, P; Bernas, T; Zarębski, M; Biela, E; Zhao, H; Darzynkiewicz, Z; Dobrucki, J W

2013-10-01

A method of quantitative analysis of spatial (3D) relationship between discrete nuclear events detected by confocal microscopy is described and applied in analysis of a dependence between sites of DNA damage signaling (γH2AX foci) and DNA replication (EdU incorporation) in cells subjected to treatments with camptothecin (Cpt) or hydrogen peroxide (H2O2). Cpt induces γH2AX foci, likely reporting formation of DNA double-strand breaks (DSBs), almost exclusively at sites of DNA replication. This finding is consistent with the known mechanism of induction of DSBs by DNA topoisomerase I (topo1) inhibitors at the sites of collisions of the moving replication forks with topo1-DNA "cleavable complexes" stabilized by Cpt. Whereas an increased level of H2AX histone phosphorylation is seen in S-phase of cells subjected to H2O2, only a minor proportion of γH2AX foci coincide with DNA replication sites. Thus, the increased level of H2AX phosphorylation induced by H2O2 is not a direct consequence of formation of DNA lesions at the sites of moving DNA replication forks. These data suggest that oxidative stress induced by H2O2 and formation of the primary H2O2-induced lesions (8-oxo-7,8-dihydroguanosine) inhibits replication globally and triggers formation of γH2AX at various distances from replication forks. Quantitative analysis of a frequency of DNA replication sites and γH2AX foci suggests also that stalling of replicating forks by Cpt leads to activation of new DNA replication origins. © 2013 International Society for Advancement of Cytometry. Copyright © 2013 International Society for Advancement of Cytometry.

Relationship between spontaneous γH2AX foci formation and progenitor functions in circulating hematopoietic stem and progenitor cells among atomic-bomb survivors.

PubMed

Kajimura, Junko; Kyoizumi, Seishi; Kubo, Yoshiko; Misumi, Munechika; Yoshida, Kengo; Hayashi, Tomonori; Imai, Kazue; Ohishi, Waka; Nakachi, Kei; Weng, Nan-Ping; Young, Lauren F; Shieh, Jae-Hung; Moore, Malcolm A; van den Brink, Marcel R M; Kusunoki, Yoichiro

2016-05-01

Accumulated DNA damage in hematopoietic stem cells is a primary mechanism of aging-associated dysfunction in human hematopoiesis. About 70 years ago, atomic-bomb (A-bomb) radiation induced DNA damage and functional decreases in the hematopoietic system of A-bomb survivors in a radiation dose-dependent manner. The peripheral blood cell populations then recovered to a normal range, but accompanying cells derived from hematopoietic stem cells still remain that bear molecular changes possibly caused by past radiation exposure and aging. In the present study, we evaluated radiation-related changes in the frequency of phosphorylated (Ser-139) H2AX (γH2AX) foci formation in circulating CD34-positive/lineage marker-negative (CD34+Lin-) hematopoietic stem and progenitor cells (HSPCs) among 226Hiroshima A-bomb survivors. An association between the frequency of γH2AX foci formation in HSPCs and the radiation dose was observed, but the γH2AX foci frequency was not significantly elevated by past radiation. We found a negative correlation between the frequency of γH2AX foci formation and the length of granulocyte telomeres. A negative interaction effect between the radiation dose and the frequency of γH2AX foci was suggested in a proportion of a subset of HSPCs as assessed by the cobblestone area-forming cell assay (CAFC), indicating that the self-renewability of HSPCs may decrease in survivors who were exposed to a higher radiation dose and who had more DNA damage in their HSPCs. Thus, although many years after radiation exposure and with advancing age, the effect of DNA damage on the self-renewability of HSPCs may be modified by A-bomb radiation exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

Detection of DNA damage in oocytes of small ovarian follicles following phosphoramide mustard exposures of cultured rodent ovaries in vitro

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

Petrillo, Stephanie K.; Desmeules, Patrice; Truong, To-Quyen

2011-06-01

Healthy oocytes are critical for producing healthy children, but little is known about whether or not oocytes have the capacity to identify and recover from injury. Using a model ovotoxic alkylating drug, cyclophosphamide (CPA), and its active metabolite, phosphoramide mustard (PM), we previously showed that PM ({>=} 3 {mu}M) caused significant follicle loss in postnatal day 4 (PND4) mouse ovaries in vitro. We now investigate whether PM induces DNA damage in oocytes, examining histone H2AX phosphorylation ({gamma}H2AX), a marker of DNA double-strand breaks (DSBs). Exposure of cultured PND4 mouse ovaries to 3 and 0.1 {mu}M PM induced significant losses ofmore » primordial and small primary follicles, respectively. PM-induced {gamma}H2AX was observed predominantly in oocytes, in which foci of {gamma}H2AX staining increased in a concentration-dependent manner and peaked 18-24 h after exposure to 3-10 {mu}M PM. Numbers of oocytes with {>=} 5 {gamma}H2AX foci were significantly increased both 1 and 8 days after exposure to {>=} 1 {mu}M PM compared to controls. Inhibiting the kinases that phosphorylate H2AX significantly increased follicle loss relative to PM alone. In adult mice, CPA also induced follicle loss in vivo. PM also significantly decreased primordial follicle numbers ({>=} 30 {mu}M) and increased {gamma}H2AX foci ({>=} 3 {mu}M) in cultured PND4 Sprague-Dawley rat ovaries. Results suggest oocytes can detect PM-induced damage at or below concentrations which cause significant follicle loss, and there are quantitative species-specific differences in sensitivity. Surviving oocytes with DNA damage may represent an increased risk for fertility problems or unhealthy offspring.« less

Genotoxicity evaluation of carbon monoxide and 1, 3-butadiene using a new joint technology - the in vitro γH2AX HCS assay combined with air-liquid interface system.

PubMed

Zhang, Sen; Chen, Huan; Wang, An; Liu, Yong; Hou, Hongwei; Hu, Qingyuan

2018-05-21

To investigate the genotoxicity of gaseous toxicants CO and 1,3-butadiene in vitro, a novel combination technology-the in vitro γH2AX high content screening assay combined with air-liquid interface system was established. The results showed that this new technology was available and effective. Based on the joint technology, genotoxicity of CO and 1,3-butadiene was evaluated further in this study. The results showed that treatment concentrations (0, 20%,40%, 80% and 100%, v/v) and exposure time (15, 30, 45, 60 and 90 min) of CO both had no statistically significant effects on the induction of γH2AX (p > 0.05). However, 1,3-butadiene can induce significant γH2AX (p < 0.01) in A549 cells in a dose/time-dependent manner both in the absence and presence of rat liver S9. When the concentrations of 1,3-butadiene were more than 80%, a higher γH2AX level could be induced than the 1.5-fold of vehicle controls after 1 h of treatment. Overall, this new technology can be used a complementary tool to evaluate the genotoxicity of airborne toxicants in vitro based on the in vitro γH2AX high content screening assay combined with air-liquid interface system. Based on the joint technology, CO was not genotoxic in A549 cells, while 1,3-butadiene showed significant genotoxicity in the dose/time-dependency on the induction of γH2AX.

Relationship between spontaneous γH2AX foci formation and progenitor functions in circulating hematopoietic stem and progenitor cells among atomic-bomb survivors

PubMed Central

Kajimura, Junko; Kyoizumi, Seishi; Kubo, Yoshiko; Misumi, Munechika; Yoshida, Kengo; Hayashi, Tomonori; Imai, Kazue; Ohishi, Waka; Nakachi, Kei; Weng, Nan-ping; Young, Lauren F.; Shieh, Jae-Hung; Moore, Malcolm A.; van den Brink, Marcel R.M.; Kusunoki, Yoichiro

2016-01-01

Accumulated DNA damage in hematopoietic stem cells is a primary mechanism of aging-associated dysfunction in human hematopoiesis. About 70 years ago, atomic-bomb (A-bomb) radiation induced DNA damage and functional decreases in the hematopoietic system of A-bomb survivors in a radiation dose-dependent manner. The peripheral blood cell populations then recovered to a normal range, but accompanying cells derived from hematopoietic stem cells still remain that bear molecular changes possibly caused by past radiation exposure and aging. In the present study, we evaluated radiation-related changes in the frequency of phosphorylated (Ser-139) H2AX (γH2AX) foci formation in circulating CD34-positive/lineage marker-negative (CD34 + Lin−) hematopoietic stem and progenitor cells (HSPCs) among 226Hiroshima A-bomb survivors. An association between the frequency of γH2AX foci formation in HSPCs and the radiation dose was observed, but the γH2AX foci frequency was not significantly elevated by past radiation. We found a negative correlation between the frequency of γH2AX foci formation and the length of granulocyte telomeres. A negative interaction effect between the radiation dose and the frequency of γH2AX foci was suggested in a proportion of a subset of HSPCs as assessed by the cobblestone area-forming cell assay (CAFC), indicating that the self-renewability of HSPCs may decrease in survivors who were exposed to a higher radiation dose and who had more DNA damage in their HSPCs. Thus, although many years after radiation exposure and with advancing age, the effect of DNA damage on the self-renewability of HSPCs may be modified by A-bomb radiation exposure. PMID:27169377

The Use of Magnetic Resonance Imaging in Axial Spondyloarthritis: Time to Bridge the Gap Between Radiologists and Rheumatologists.

PubMed

Bennett, Alexander N; Marzo-Ortega, Helena; Kaur-Papadakis, Daljit; Rehman, Amer

2017-06-01

Magnetic resonance imaging (MRI) is involved in the assessment of axial spondyloarthritis (axSpA); however, anecdotal evidence suggests diverse practice among radiologists. The objective of this study was to describe current practice in the use of MRI for assessment of axSpA by UK radiologists. Six hundred ninety-nine UK radiologists were invited to complete an online survey. Availability of MR scanners, familiarity with axSpA disease-specific lesions, and MRI protocols and definitions of positive sacroiliac joint (SIJ) or spinal MRI were assessed. Two-hundred sixty-nine radiologists (38%) from 131/180 (73%) acute UK National Health Service trusts/health boards responded. MRI waiting times < 2 months were reported by 90% of radiologists. Twenty-nine radiologists (11%) used contrast as standard, 256 (91%) used T1 and short-tau inversion recovery, and 172 (64%) also used T2 sequences. Five percent scanned only SIJ, 33% scanned SIJ and lumbar spine, 29% scanned SIJ and thoracolumbar spine, and 30% scanned SIJ and the whole spine. Mean scan time was 34 min. Eighteen percent did not use the subchondral bone marrow edema of the SIJ to help diagnose axSpA and 18% did not use the inflammatory vertebral corner lesions to assist diagnosis. Awareness of axSpA was reported by 75% of radiologists, and awareness of definitions for positive MRI of SIJ and spine by 31% and 25%, respectively. These data highlight the need for better rheumatology-radiology collaboration on the identification of diagnostic axSpA MRI lesions and support the need for a consensus on the most appropriate MRI protocols for the assessment of axSpA.

Quantitative Evaluation of Brain Stem Atrophy Using Magnetic Resonance Imaging in Adult Patients with Alexander Disease.

PubMed

Yoshida, Tomokatsu; Yasuda, Rei; Mizuta, Ikuko; Nakagawa, Masanori; Mizuno, Toshiki

2017-01-01

Brain MRI in adult patients with Alexander disease (AxD) mainly shows atrophy in the medulla oblongata. However, currently there is no quantitative standard for assessing this atrophy. In this study, we quantitatively evaluated the brain stem of AxD patients with glial fibrillary acidic protein (GFAP) mutation using conventional MRI to evaluate its usefulness as an aid to diagnosing AxD in daily clinical practice. Nineteen AxD patients with GFAP mutation were compared with 14 patients negative for GFAP mutation in whom AxD was suspected due to "atrophy of the medulla oblongata." In the GFAP mutation-positive group, the sagittal diameter of the medulla oblongata, the ratio of the diameter of the medulla oblongata to that of the midbrain (MO/MB), and the ratio of the sagittal diameter of the medulla oblongata to that of the pons (MO/Po) were significantly smaller compared to those of the GFAP mutation-negative group (p < 0.01). The sensitivity and specificity of each parameter were 87.5 and 92.3%, 91.7 and 81.3%, and 88.2 and 100% with a sagittal diameter of the medulla oblongata <9.0 mm, MO/MB <0.60, and sagittal MO/Po <0.46, respectively. These parameters can provide very useful information to differentially diagnose AxD from other disorders associated with brain stem atrophy in adult patients. © 2017 S. Karger AG, Basel.

Finger millet arabinoxylan protects mice from high-fat diet induced lipid derangements, inflammation, endotoxemia and gut bacterial dysbiosis.

PubMed

Sarma, Siddhartha Mahadeva; Singh, Dhirendra Pratap; Singh, Paramdeep; Khare, Pragyanshu; Mangal, Priyanka; Singh, Shashank; Bijalwan, Vandana; Kaur, Jaspreet; Mantri, Shrikant; Boparai, Ravneet Kaur; Mazumder, Koushik; Bishnoi, Mahendra; Bhutani, Kamlesh Kumar; Kondepudi, Kanthi Kiran

2018-01-01

Arabinoxylan (AX), a non-starch polysaccharide extracted from cereals such as wheat, rice and millets, is known to impart various health promoting effects. Our earlier study suggested that finger millet (FM) could ameliorate high fat diet (HFD)-induced metabolic derangements. The present study is aimed to evaluate the effect of FM-AX supplementation, a key bioactive from finger millet, on HFD-induced metabolic and gut bacterial derangements. Male Swiss albino mice were fed with normal chow diet (NPD) or HFD (60%kcal from fat) for 10 weeks. FM-AX was orally supplemented at doses of 0.5 and 1.0g/kg bodyweight on every alternate day for 10 weeks. Glucose tolerance, serum hormones, hepatic lipid accumulation and inflammation, white adipose tissue marker gene expression, adipocyte size and inflammation; metagenomic alterations in cecal bacteria; cecal short chain fatty acids and colonic tight junction gene expressions were studied. FM-AX supplementation prevented HFD-induced weight gain, alerted glucose tolerance and serum lipid profile, hepatic lipid accumulation and inflammation. Hepatic and white adipose tissue gene expressions were beneficially modulated. Further, AX supplementation prevented metagenomic alterations in cecum; improved ileal and colonic health and overall prevented metabolic endotoxemia. Present work suggests that AX from finger millet can be developed as a nutraceutical for the management of HFD- induced obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

Spotlight on certolizumab pegol in the treatment of axial spondyloarthritis: efficacy, safety and place in therapy.

PubMed

Marin, Josefina; Acosta Felquer, María Laura; Soriano, Enrique R

2018-01-01

Certolizumab pegol (CZP) is a pegylated humanized tumor necrosis factor-α inhibitor (TNFi) approved for the treatment of ankylosing spondylitis (AS) in the USA and for AS and non-radiographic axial spondyloarthritis (nr-axSpA) in Europe and in some Latin American countries. CZP lacks Fc region, preventing complement fixation and cytotoxicity mediated by antibody; CZP does not actively cross the placenta, unlike other TNFi. RAPID-axSpA study is a Phase III trial conducted in patients with AS and nr-axSpA as double blind and placebo controlled to week 24, dose blind to week 48 and open label to week 204. Of a total of 325 patients recruited, 107 patients were assigned to placebo and 218 patients to CZP (111 to CZP 200 mg Q2W, 107 to CZP 400 mg Q4W). Improvements in axial involvement, joint involvement, enthesitis and quality of life were reported in patients treated with CZP. Safety profile was like that reported for other TNFi in axSpA patients. In this article, we summarized the pharmacology and we reviewed the efficacy and tolerability of this drug for the treatment of axSpA. Some special considerations of CZP during pregnancy are included. CZP, the latest TNFi to be approved, showed efficacy in all manifestations of AS and nr-axSpA.

Relationship between optimism and quality of life in patients with two chronic rheumatic diseases: axial spondyloarthritis and chronic low back pain: a cross sectional study of 288 patients.

PubMed

Kreis, Sarah; Molto, Anna; Bailly, Florian; Dadoun, Sabrina; Fabre, Stéphanie; Rein, Christopher; Hudry, Christophe; Zenasni, Franck; Rozenberg, Sylvie; Pertuiset, Edouard; Fautrel, Bruno; Gossec, Laure

2015-06-10

Axial Spondyloarthritis (AxSpA) and chronic low back pain are rheumatic diseases that impact patients' health-related quality of life (HRQoL). In other chronic conditions, HRQoL was positively associated with dispositional optimism, a personality trait. The objective was to explore the relationship between optimism and HRQoL in these two diseases. A cross-sectional study was performed in 2 tertiary care hospitals and 2 private practices in France. Patients had definite AxSpA or chronic low back pain according to the rheumatologist. A generic HRQoL questionnaire (Short Form, SF-12) with physical and mental composite scores (PCS and MCS respectively) and an optimism questionnaire (the Life Orientation Test-revised, LOT-R) were collected. Analyses included non-parametric correlations and multiple regression analyses to study the effect of optimism on PCS and MCS. In all, 288 (199 AxSpA and 89 low back pain) patients were included: mean age, 47.3 ± 11.9 years, 48.6 % were males. Pain levels (0-10) were 4.5 ± 2.4 and 4.3 ± 2.4 in AxSpA and LOW BACK PAIN patients, respectively. HRQoL was similarly altered in both diseases, for both physical and mental composite scores (mean PCS: 43.7 ± 8.2 vs. 41.9 ± 7.1; mean 45.9 ± 7.8 vs. 46.7 ± 8.1 for AxSpA and low back pain respectively). Optimism was moderate and similar in both populations. Optimism was positively correlated to MCS in both diseases (rho = 0.54 and 0.58, respectively, both p <0.01) and these relations persisted in multivariate analyses (beta = 1.03 and 1.40, both p <0.0001). Optimism was similar in these 2 chronic diseases and was an explanatory factor of the mental component of HRQoL, but not physical HRQoL. Physical HRQoL may reflect more the disease process than character traits.

Physical Activity Assessment Using an Activity Tracker in Patients with Rheumatoid Arthritis and Axial Spondyloarthritis: Prospective Observational Study

PubMed Central

Servy, Hervé; Molto, Anna; Sellam, Jérémie; Foltz, Violaine; Gandjbakhch, Frédérique; Hudry, Christophe; Mitrovic, Stéphane; Fautrel, Bruno; Gossec, Laure

2018-01-01

Background Physical activity can be tracked using mobile devices and is recommended in rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) management. The World Health Organization (WHO) recommends at least 150 min per week of moderate to vigorous physical activity (MVPA). Objective The objectives of this study were to assess and compare physical activity and its patterns in patients with RA and axSpA using an activity tracker and to assess the feasibility of mobile devices in this population. Methods This multicentric prospective observational study (ActConnect) included patients who had definite RA or axSpA, and a smartphone. Physical activity was assessed over 3 months using a mobile activity tracker, recording the number of steps per minute. The number of patients reaching the WHO recommendations was calculated. RA and axSpA were compared, using linear mixed models, for number of steps, proportion of morning steps, duration of total activity, and MVPA. Physical activity trajectories were identified using the K-means method, and factors related to the low activity trajectory were explored by logistic regression. Acceptability was assessed by the mean number of days the tracker was worn over the 3 months (ie, adherence), the percentage of wearing time, and by an acceptability questionnaire. Results A total of 157 patients (83 RA and 74 axSpA) were analyzed; 36.3% (57/157) patients were males, and their mean age was 46 (standard deviation [SD] 12) years and mean disease duration was 11 (SD 9) years. RA and axSpA patients had similar physical activity levels of 16 (SD 11) and 15 (SD 12) min per day of MVPA (P=.80), respectively. Only 27.4% (43/157) patients reached the recommendations with a mean MVPA of 106 (SD 77) min per week. The following three trajectories were identified with constant activity: low (54.1% [85/157] of patients), moderate (42.7% [67/157] of patients), and high (3.2% [5/157] of patients) levels of MVPA. A higher body mass index was significantly related to less physical activity (odds ratio 1.12, 95% CI 1.11-1.14). The activity trackers were worn during a mean of 79 (SD 17) days over the 90 days follow-up. Overall, patients considered the use of the tracker very acceptable, with a mean score of 8 out 10. Conclusions Patients with RA and axSpA performed insufficient physical activity with similar levels in both groups, despite the differences between the 2 diseases. Activity trackers allow longitudinal assessment of physical activity in these patients. The good adherence to this study and the good acceptability of wearing activity trackers confirmed the feasibility of the use of a mobile activity tracker in patients with rheumatic diseases. PMID:29295810

Extremes of Moving Averages of Stable Processes.

DTIC Science & Technology

1976-10-01

for -::~e contiriuous-tir e case, a result on sa~ n1e :-~~t~i continuity of stable ~rccess~s is obtained. J~.I3 1°70 subject classification: Prinary C...we let ~(x,y) = ~~~~ 6~(x,y) where 6~(x,y) = min(l/3, h(c ~ x,c1y)) and h(c.x~c~y) is the quantity given on p. 113- 115 of Lindvall’s paper, modified...that ~~~~~ < for all k1. The latter part of the condition perhaps needs some motivation. Suppose that a(X) is continuously differentiable , except

Wee1 Kinase Inhibitor AZD1775 Radiosensitizes Hepatocellular Carcinoma Regardless of TP53 Mutational Status Through Induction of Replication Stress

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

Cuneo, Kyle C., E-mail: kcuneo@umich.edu; Morgan, Meredith A.; Davis, Mary A.

2016-06-01

Purpose: Wee1 kinase inhibitors are effective radiosensitizers in cells lacking a G{sub 1} checkpoint. In this study we examined the potential effect of Wee1 kinase inhibition on inducing replication stress in hepatocellular carcinoma (HCC). Methods and Materials: Five independent datasets from the Oncomine database comparing gene expression in HCC compared to normal tissue were combined and specific markers associated with Wee1 sensitivity were analyzed. We then performed a series of in vitro experiments to study the effect of Wee1 inhibition on irradiated HCC cell lines with varying p53 mutational status. Clonogenic survival assays and flow cytometry using anti-γH2AX and phospho-histone H3more » antibodies with propidium iodide were performed to study the effect of AZD1775 on survival, cell cycle, and DNA repair. Additionally, nucleoside enriched medium was used to examine the effect of altering nucleotide pools on Wee1 targeted radiation sensitization. Results: Our analysis of the Oncomine database found high levels of CDK1 and other cell cycle regulators indicative of Wee1 sensitivity in HCC. In our in vitro experiments, treatment with AZD1775 radiosensitized and chemosensitized Hep3B, Huh7, and HepG2 cell lines and was associated with delayed resolution of γH2AX foci and the induction of pan-nuclear γH2AX staining. Wee1 inhibition attenuated radiation-induced G{sub 2} arrest in the Hep3B (TP53 null) and Huh7 (TP53 mutant) cell lines but not in the TP53 wild-type cell line HepG2. Supplementation with nucleosides reversed the radiation-sensitizing effect of AZD1775 and reduced the amount of cells with pan-nuclear γH2AX staining after radiation. Conclusions: Radiation sensitization with Wee1 inhibition occurs in cells regardless of their p53 mutational status. In this study we show for the first time that replication stress via the overconsumption of nucleotides plays an important role in AZD1775-induced radiation sensitization.« less

Genotoxicity testing: Comparison of the γH2AX focus assay with the alkaline and neutral comet assays.

PubMed

Nikolova, Teodora; Marini, Federico; Kaina, Bernd

2017-10-01

Genotoxicity testing relies on the quantitative measurement of adverse effects, such as chromosome aberrations, micronuclei, and mutations, resulting from primary DNA damage. Ideally, assays will detect DNA damage and cellular responses with high sensitivity, reliability, and throughput. Several novel genotoxicity assays may fulfill these requirements, including the comet assay and the more recently developed γH2AX assay. Although they are thought to be specific for genotoxicants, a systematic comparison of the assays has not yet been undertaken. In the present study, we compare the γH2AX focus assay with the alkaline and neutral versions of the comet assay, as to their sensitivities and limitations for detection of genetic damage. We investigated the dose-response relationships of γH2AX foci and comet tail intensities at various times following treatment with four prototypical genotoxicants, methyl methanesulfonate (MMS), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), mitomycin C, and hydrogen peroxide (H 2 O 2 ) and we tested whether there is a correlation between the endpoints, i.e., alkali-labile sites and DNA strand breaks on the one hand and the cell's response to DNA double-strand breaks and blocked replication forks on the other. Induction of γH2AX foci gave a linear dose response and all agents tested were positive in the assay. The increase in comet tail intensity was also a function of dose; however, mitomycin C was almost completely ineffective in the comet assay, and the doses needed to achieve a significant effect were somewhat higher for some treatments in the comet assay than in the γH2AX foci assay, which was confirmed by threshold analysis. There was high correlation between tail intensity and γH2AX foci for MMS and H 2 O 2 , less for MNNG, and none for mitomycin C. From this we infer that the γH2AX foci assay is more reliable, sensitive, and robust than the comet assay for detecting genotoxicant-induced DNA damage. Copyright © 2017 Elsevier B.V. All rights reserved.

Short-term markers of DNA damage among roofers who work with hot asphalt.

PubMed

Serdar, Berrin; Brindley, Stephen; Dooley, Greg; Volckens, John; Juarez-Colunga, Elizabeth; Gan, Ryan

2016-10-20

Roofers are at increased risk for various malignancies and their occupational exposures to polycyclic aromatic hydrocarbons (PAHs) have been considered as important risk factors. The overall goal of this project was to investigate the usefulness of phosphorylated histone H2AX (γH2AX) as a short-term biomarker of DNA damage among roofers. Blood, urine, and dermal wipe samples were collected from 20 roofers who work with hot asphalt before and after 6 h of work on Monday and Thursday of the same week (4 sampling periods). Particle-bound and gas-phase PAHs were collected using personal monitors during work hours. γH2AX was quantified in peripheral lymphocytes using flow cytometry and 8-hydroxy-2-deoxyguanosine (8-OHdG) was assessed in urine using ELISA. General linear mixed models were used to evaluate associations between DNA damage and possible predictors (such as sampling period, exposure levels, work- and life-style factors). Differences in mean biomarker and DNA damage levels were tested via ANOVA contrasts. Exposure measurements did not show an association with any of the urinary biomarkers or the measures of DNA damage. Naphthalene was the most abundant PAH in gas-phase, while benzo(e)pyrene was the most abundant particle-bound PAH. Post-shift levels of γH2AX and 8-OHdG were higher on both study days, when compared to pre-shift levels. Cigarette smoking was a predictor of γH2AX and urinary creatinine was a predictor of urinary 8-OHdG. Between-subject variance to total variance ratio was 35.3 % for γH2ax and 4.8 % for 8-OHdG. γH2AX is a promising biomarker of DNA damage in occupational epidemiology studies. It has a lower within-subject variation than urinary 8-OHdG and can easily be detected in large scale groups. Future studies that explore the kinetics of H2AX phosphorylation in relation to chemical exposures may reveal the transient and persistent nature of this sensitive biomarker of early DNA damage.

Microwave superheated water and dilute alkali extraction of brewers' spent grain arabinoxylans and arabinoxylo-oligosaccharides.

PubMed

Coelho, Elisabete; Rocha, M Angélica M; Saraiva, Jorge A; Coimbra, Manuel A

2014-01-01

Microwave superheated water extractions (MWE) were performed to evaluate the feasibility of this technology for quantitative recovery of the arabinoxylans (AX) or arabinoxylo-oligosaccharides (AXOS) from brewers' spent grain (BSG). The AX+AXOS yield increased with the increase of the temperature in the range from 140 to 210 °C during 2 min. The higher temperatures promoted depolymerisation, debranching, and deesterification of the polysaccharides, with formation of brown products. The conditions that promote a compromise between the yield and the structure obtained, minimizing the thermal degradation of the fractions extracted by MWE are the following: (1) 140 °C, to remove the residual starch mixed with β-glucans; (2) Suspension of the residue left in water and treated at 180 °C; (3) suspension of the residue in 0.1 M KOH and treated at 180 °C. Using this sequential procedure, it was possible to extract 62% of BSG AX+AXOS, presenting degrees of polymerization ranging between 7 and 24 xylose residues, and a degree of phenolic acids esterification between 5 and 21%. The structural variability obtained by MWE allows defining specific types of compounds for different applications and uses depending on the extraction conditions used. Copyright © 2013 Elsevier Ltd. All rights reserved.

The prevalence and clinical characteristics of nonradiographic axial spondyloarthritis among patients with inflammatory back pain in rheumatology practices: a multinational, multicenter study.

PubMed

Burgos-Varga, Ruben; Wei, James Cheng-Chung; Rahman, Mahboob U; Akkoc, Nurullah; Haq, Syed Atiqul; Hammoudeh, Mohammed; Mahgoub, Ehab; Singh, Ena; Llamado, Lyndon John; Shirazy, Khalid; Kotak, Sameer; Hammond, Constance; Pedersen, Ron; Shen, Qi; Vlahos, Bonnie

2016-06-07

Patients with ankylosing spondylitis (AS), who by definition have radiographic sacroiliitis, typically experience symptoms for a decade or more before being diagnosed. Yet, even patients without radiographic sacroiliitis (i.e., nonradiographic axial spondyloarthritis [nr-axSpA]) report a significant disease burden. The primary objective of this study was to estimate the prevalence and clinical characteristics of nr-axSpA among patients with inflammatory back pain (IBP) in rheumatology clinics in a number of countries across the world. A secondary objective was to estimate the prevalence of IBP among patients with chronic low back pain (CLBP). Data were collected from 51 rheumatology outpatient clinics in 19 countries in Latin America, Africa, Europe, and Asia. As consecutive patients with CLBP (N = 2517) were seen by physicians at the sites, their clinical histories were evaluated to determine whether they met the new Assessment of SpondyloArthritis international Society criteria for IBP. For those who did, their available clinical history (e.g., family history, C-reactive protein [CRP] levels) was documented in a case report form to establish whether they met criteria for nr-axSpA, AS, or other IBP. Patients diagnosed with nr-axSpA or AS completed patient-reported outcome measures to assess disease activity and functional limitations. A total of 2517 patients with CLBP were identified across all sites. Of these, 974 (38.70 %) fulfilled the criteria for IBP. Among IBP patients, 29.10 % met criteria for nr-axSpA, and 53.72 % met criteria for AS. The prevalence of nr-axSpA varied significantly by region (p < 0.05), with the highest prevalence reported in Asia (36.46 %) and the lowest reported in Africa (16.02 %). Patients with nr-axSpA reported mean ± SD Ankylosing Spondylitis Disease Activity Scores based on erythrocyte sedimentation rate and CRP of 2.62 ± 1.17 and 2.52 ± 1.21, respectively, indicating high levels of disease activity (patients with AS reported corresponding scores of 2.97 ± 1.13 and 2.93 ± 1.18). Similarly, the overall Bath Ankylosing Spondylitis Disease Activity Index score of 4.03 ± 2.23 for patients with nr-axSpA (4.56 ± 2.17 for patients with AS) suggested suboptimal disease control. These results suggest that, in the centers that participated in the study, 29 % of patients with IBP met the criteria for nr-axSpA and 39 % of patients with CLBP had IBP. The disease burden in nr-axSpA is substantial and similar to that of AS, with both groups of patients experiencing inadequate disease control. These findings suggest the need for early detection of nr-axSpA and initiation of available treatment options to slow disease progression and improve patient well-being.

Depolymerization degree of water-extractable arabinoxylans in rye bread: characteristics of inbred lines used for breeding of bread cultivars.

PubMed

Cyran, Malgorzata R; Ceglińska, Alicja; Kolasińska, Irena

2012-09-05

The water-extractable arabinoxylans (WE AXs) present in rye bread govern its viscous properties, which may be related to reduced risk of cardiovascular diseases and diabetes. Breads made from rye cultivars generally exhibit higher AX-dependent extract viscosities (Cyran, M. R.; Saulnier, L. Food Chemistry2012, 131, 667-676) when compared with those produced from inbred lines used for their breeding. To give further details about this trend, the WE AXs were isolated from breads of lines and structurally characterized by HPSEC and (1)H NMR spectroscopy. The extract viscosities of endosperm and whole-meal breads were usually comparable, in contrast to those made from rye cultivars with higher viscosity of endosperm bread. The WE AXs present in breads obtained from inbred lines were characterized by the higher degradation degrees than those in breads from cultivars, as indicated by their HPSEC-RI profiles. This was associated with considerably lower proportions of 2-Xylp in their backbones. Besides, a level of endoxylanase activity in flours from inbred lines was much higher than that in flours from cultivars. Breeding of hybrid rye cultivars for production of high-viscosity bread requires the proper components. They may be preliminarily selected from populations with high WE AX contents and relatively low levels of endoxylanase activity by using the overall viscosity test for starting flours. However, further measurement of AX-dependent extract viscosity in test breads made from such lines may verify their usefulness completely.

Complementary medicine for axial spondyloarthritis: is there any scientific evidence?

PubMed

Danve, Abhijeet; Deodhar, Atul A

2018-07-01

Majority of patients with axial spondyloarthritis (axSpA) report use of complementary and alternative medicine (CAM) therapies before and even after the diagnosis, due to perceived efficacy and wide-spread belief that these modalities lack side effects. In this review, we describe the available scientific evidence for the CAM therapies in axSpA. Clinical trials of the CAM therapies in axSpA are generally hampered by small sample size, short duration, difficulties in blinding, lack of control groups and strong placebo effect. Nonetheless, exercise programs like Pilates and mind-body techniques such as Tai Chi may have favorable effect on the disease activity and function. Although not yet confirmed, the modulation of the microbiome with the help of probiotics or fecal transplant has face validity given the evolving scientific rationale. Diet has only limited role in the management of axSpA. Deep tissue massage, omega-3 fatty acids and Stanger bath were found to be useful in small studies. CAM therapies are not always entirely well tolerated, particularly the manipulative techniques like chiropractic and Tui-na in patients with advanced disease and osteoporosis. There are no trials of yoga in axSpA despite the wider acceptance and use of yoga as an effective mind-body technique. Larger and better quality clinical trials of CAM therapies are needed to confirm their efficacy and safety in the management of axSpA and to include them in the 'mainstream' medicine.

Modeling a Hall Thruster from Anode to Plume Far Field

DTIC Science & Technology

2008-12-31

Two dimensional ax symmetric simulations of xenon plasma plume flow fields from a D55 Anode layer Hall thruster is performed. A hybrid particle-fluid...method is used for the Simulations. The magnetic field surrounding the Hall thruster exit is included in the Calculation. The plasma properties

ENVIRONMENTAL TECHNOLOGY VERIFICATION REPORT - BAGHOUSE FILTRATION PRODUCTS - BASF CORPORATION AX/BA-14/9-SAXP FILTER SAMPLE

EPA Science Inventory

Baghouse filtration products (BFPs) were evaluated by the Air Pollution Control Technology (APCT) pilot of the Environmental Technology Verification (ETV) Program. The performance factor verified was the mean outlet particle concentration for the filter fabric as a function of th...

Control of nonlinear systems represented in quasilinear form. Ph.D. Thesis, 1994 Final Report

NASA Technical Reports Server (NTRS)

Coetsee, Josef A.

1993-01-01

Methods to synthesize controllers for nonlinear systems are developed by exploiting the fact that under mild differentiability conditions, systems of the form: x-dot = f(x) + G(x)u can be represented in quasilinear form, viz: x-dot = A(x)x + B(x)u. Two classes of control methods are investigated. The first is zero-look-ahead control, where the control input depends only on the current values of A(x) and B(x). For this case the control input is computed by continuously solving a matrix Riccati equation as the system progresses along a trajectory. The second is controllers with look-ahead, where the control input depends on the future behavior of A(x) and B(x). These controllers use the similarity between quasilinear systems and linear time varying systems to find approximate solutions to optimal control type problems. The methods that are developed are not guaranteed to be globally stable. However in simulation studies they were found to be useful alternatives for synthesizing control laws for a general class of nonlinear systems.

Stability of astaxanthin-loaded nanostructured lipid carriers in beverage systems.

PubMed

Tamjidi, Fardin; Shahedi, Mohammad; Varshosaz, Jaleh; Nasirpour, Ali

2018-01-01

Nanostructured lipid carriers (NLCs) offer many potential benefits for incorporating lipophilic molecules into clear to opaque food systems. This study examined the stability of astaxanthin-loaded NLCs (Ax-NLCs) in model (solutions with 0 or 12% sucrose; pH 3, 7), semi-actual (whey) and actual (non-alcoholic beer) beverages during 30-60 days storage at 6 or 20 °C. Ax-NLCs (Z-average size: 94 nm), containing α-tocopherol and EDTA as antioxidants, were stabilised with Tween 80 and lecithin, and mixed with the aforementioned beverages at the volume ratio of 3:97. The presence of sucrose, improved the physical stability of Ax-NLCs in acidic model beverage. No astaxanthin loss and particle size growth were observed for Ax-NLCs-added whey. Carbonation and/or thermal pasteurisation of NLCs-added beer led to a major increase in its particles size and astaxanthin loss. Stability of Ax-NLCs in non-pasteurised CO 2 -free beer improved at low storage temperature. The organoleptic quality of NLCs-added beers was still acceptable. These results indicate that NLCs containing hydrophobic nutraceuticals have potential to be used for functional beverages/foods development. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Durability Testing of Tank Track Rubber Compounds under Cyclic Loading

DTIC Science & Technology

1987-10-15

depiction of time-to-failure vs applied ( engineering ) stress for 15TP-14AX rubber compounds in creep experiments at 23"C. (After McKenna (1...behavior of the 15TP-14AX rubber was carried out at 23, 75, 125 and 175 OC. The logarithm of the time to failure vs. the applied ( engineering ) stress is...4 3I. I I 5 10 15 a/MPa Figure 3-7 Semilogarith±ic depiction of time-to--failure vs applied ( engineering ) stress for 15TP-14AX rubber compounds in

Perceptual learning transfer in an appetitive Pavlovian task.

PubMed

Artigas, Antonio A; Prados, Jose

2017-06-01

In two experiments, rats were given intermixed or blocked preexposure to two similar compound stimuli, AX and BX. Following preexposure, conditioning trials took place in which AX (Experiment 1) or a novel compound stimulus NX (Experiment 2) was paired with a food-unconditioned stimulus in an appetitive Pavlovian preparation. Animals that were given alternated preexposure showed lower generalization from AX to BX (Experiment 1) and from NX to a new compound, ZX (Experiment 2), than animals that were given blocked preexposure, a perceptual learning and a perceptual learning transfer effect, respectively.

Gamma-H2AX as a biomarker of DNA damage induced by ionizing radiation in targeted and bystander human artificial skin models and peripheral blood lymphocytes

NASA Astrophysics Data System (ADS)

Redon, Christophe; Dickey, Jennifer; Bonner, William; Sedelnikova, Olga

Ionizing radiation (IR) exposure is inevitable. In addition to exposure from cosmic rays, the sun and radioactive substances, modern society has created new sources of radiation exposure such as space and high altitude journeys, X-ray diagnostics, radiological treatments and the increasing threat of radiobiological terrorism. For these reasons, a reliable, reproducible and sensitive assessment of dose and time exposure to IR is essential. We developed a minimally invasive diagnostic test for IR exposure based on detection of a phosphorylated variant of histone H2AX (gamma-H2AX), which occurs specifically at sites of DNA double-strand breaks (DSBs). The phosphorylation of thousands of H2AX molecules forms a gamma-H2AX focus in the chromatin flanking the DSB site that can be detected in situ. We analyzed gamma- H2AX focus formation in both directly irradiated cells as well as in un-irradiated "bystanders" in close contact with irradiated cells. In order to insure minimal invasiveness, we examined commercially available artificial skin models as a surrogate for human skin biopsies as well as peripheral blood lymphocytes. In human skin models, cells in a thin plane were microbeamirradiated and gamma-H2AX formation was measured both in irradiated and in distal bystander cells over time. In irradiated cells DSB formation reached a maximum at 15-30 minutes post- IR and then declined within several hours; all cells were affected. In marked contrast, the incidence of DSBs in bystander cells reached a maximum by 12-48 hours post-irradiation, gradually decreasing over the 7 day time course. At the maxima, 40-60% of bystander cells were affected. Similarly, we analyzed blood samples exposed to IR ex vivo at doses ranging from 0.02 to 3 Gy. The amount of DNA damage was linear in respect to radiation dose and independent of the age or sex of the blood donor. The method is highly reproducible and highly sensitive. In directly irradiated cells, the number of gamma-H2AX foci peaked 30 min after irradiation and then declined at a relatively steady pace as the cell repaired the DNA damage. Radiation effects were still detectable after 48 hrs for doses greater than 1 Gy and remained linear to initial dose. Activated bystander lymphocytes cultured with media from irradiated lymphocytes exhibited a two-fold increased damage response as seen by gamma- H2AX formation. The effect reached a maximum 3 hrs post-exposure and was retained for over 24 hrs. Thus, detection of gamma-H2AX formation to determine DNA damage in a minimally invasive skin test and a non-invasive blood test could be useful and promising tools to analyze direct and indirect effects of radiation exposure.

Study protocol for a cluster randomized controlled trial to evaluate a referral strategy for axial spondyloarthritis in young primary care patients with chronic low back pain; an impact study.

PubMed

van Hoeven, Lonneke; Vergouwe, Yvonne; Koes, Bart W; Hazes, Johanna M W; Weel, Angelique E A M

2016-07-12

Axial spondyloarthritis (axSpA) is a disabling inflammatory joint disease with chronic low back pain (CLBP) as leading symptom. Recognizing axSpA in the large amount of CLBP patients is difficult for general practioners (GP). This evaluation aims to assess the effect of a referral strategy for axSpA in young primary care patients with CLBP by comparing the use of the strategy with usual care. The effect is measured at three different levels; by patient reported outcomes (the clinical effect), process and costs evaluation. This study design is a cluster randomized controlled trial with GP as clusters. GPs throughout the Netherlands are invited to participate and randomized to either the intervention or the control group. Patients from participating GPs are invited to participate if they have ever been registered with low back pain, without radiation (ICPC L03) and aged 18-45 years. To be included in the study, patients need to have current low back pain and chronic low back pain (>12 weeks). In the intervention arm a referral strategy for axSpA will be applied in CLBP patients, in the control arm care as usual will be provided for CLBP patients. The referral strategy consists of four easy to use variables. All are questions about the back pain complaints of the patients. Data is prospectively collected in an online database at baseline (T0), 4 months (T1), 12 months (T2) and 24 months (T3). After time point T1 (4 months) patients from the control group will also receive the intervention i.e. the application of a referral strategy for axSpA. The effect of the referral strategy is measured at three different levels, by patient outcomes (e.g. pain scores, quality of life), process measures (e.g. number of axSpA diagnoses by rheumatologists) and by costs (work productivity and health care resources use). Our primary outcome is the Roland Morris Disability Questionnaire after 4 months, secondary outcomes are pain and quality of life. Costs will be assessed before and after the use of the referral strategy, to estimate if the use of the strategy will lead to a reduction in health care costs and improvement in work participation. It is anticipated that using the axSpA referral strategy for primary care CLBP patients will increase the quality of life of CLBP patients, will result in more (correct) diagnoses of axSpA by the rheumatologists, and will be cost-effective. Ultimately, the results of this study may contribute to the startup of a national implementation of the axSpA referral strategy to identify timely CLBP patients with axSpA. NCT01944163 , date of registration; September 6, 2013 (Clinicaltrials.gov).

Nanostructure of DNA repair foci revealed by superresolution microscopy.

PubMed

Sisario, Dmitri; Memmel, Simon; Doose, Sören; Neubauer, Julia; Zimmermann, Heiko; Flentje, Michael; Djuzenova, Cholpon S; Sauer, Markus; Sukhorukov, Vladimir L

2018-06-12

Induction of DNA double-strand breaks (DSBs) by ionizing radiation leads to formation of micrometer-sized DNA-repair foci, whose organization on the nanometer-scale remains unknown because of the diffraction limit (∼200 nm) of conventional microscopy. Here, we applied diffraction-unlimited, direct stochastic optical-reconstruction microscopy ( dSTORM) with a lateral resolution of ∼20 nm to analyze the focal nanostructure of the DSB marker histone γH2AX and the DNA-repair protein kinase (DNA-PK) in irradiated glioblastoma multiforme cells. Although standard confocal microscopy revealed substantial colocalization of immunostained γH2AX and DNA-PK, in our dSTORM images, the 2 proteins showed very little (if any) colocalization despite their close spatial proximity. We also found that γH2AX foci consisted of distinct circular subunits ("nanofoci") with a diameter of ∼45 nm, whereas DNA-PK displayed a diffuse, intrafocal distribution. We conclude that γH2AX nanofoci represent the elementary, structural units of DSB repair foci, that is, individual γH2AX-containing nucleosomes. dSTORM-based γH2AX nanofoci counting and distance measurements between nanofoci provided quantitative information on the total amount of chromatin involved in DSB repair as well as on the number and longitudinal distribution of γH2AX-containing nucleosomes in a chromatin fiber. We thus estimate that a single focus involves between ∼0.6 and ∼1.1 Mbp of chromatin, depending on radiation treatment. Because of their ability to unravel the nanostructure of DSB-repair foci, dSTORM and related single-molecule localization nanoscopy methods will likely emerge as powerful tools in biology and medicine to elucidate the effects of DNA damaging agents in cells.-Sisario, D., Memmel, S., Doose, S., Neubauer, J., Zimmermann, H., Flentje, M., Djuzenova, C. S., Sauer, M., Sukhorukov, V. L. Nanostructure of DNA repair foci revealed by superresolution microscopy.

Induction and disappearance of γH2AX foci and formation of micronuclei after exposure of human lymphocytes to ⁶⁰Co γ-rays and p(66)+ Be(40) neutrons.

PubMed

Vandersickel, Veerle; Beukes, Philip; Van Bockstaele, Bram; Depuydt, Julie; Vral, Anne; Slabbert, Jacobus

2014-02-01

To investigate both the formation of micronuclei (MN) and the induction and subsequent loss of phosphorylated histone H2AX foci (γH2AX foci) after in vitro exposure of human lymphocytes to either (60)Co γ-rays or p(66)+ Be(40) neutrons. MN dose response (DR) curves were obtained by exposing isolated lymphocytes of 10 different donors to doses ranging from 0-4 Gy γ-rays or 0-2 Gy neutrons. Also, γH2AX foci DR curves were obtained following exposure to doses ranging from 0-0.5 Gy of either γ-rays or neutrons. Foci kinetics for lymphocytes for a single donor exposed to 0.5 Gy γ-rays or neutrons were studied up to 24 hours post-irradiation. Micronuclei yields following neutron exposure were consistently higher compared to that from (60)Co γ-rays. All MN yields were over-dispersed compared to a Poisson distribution. Over-dispersion was higher after neutron irradiation for all doses > 0.1 Gy. Up to 4 hours post-irradiation lower yields of neutron-induced γH2AX foci were observed. Between 4 and 24 hours the numbers of foci from neutrons were consistently higher than that from γ-rays. The half-live of foci disappearance is only marginally longer for neutrons compared to that from γ-rays. Foci formations were more likely to be over-dispersed for neutron irradiations. Although neutrons are more effective to induce MN, the absolute number of induced γH2AX foci are less at first compared to γ-rays. With time neutron-induced foci are more persistent. These findings are helpful for using γH2AX foci in biodosimetry and to understand the repair of neutron-induced cellular damage.

Insights into the Activity and Substrate Binding of Xylella fastidiosa Polygalacturonase by Modification of a Unique QMK Amino Acid Motif Using Protein Chimeras

PubMed Central

Warren, Jeremy G.; Lincoln, James E.; Kirkpatrick, Bruce C.

2015-01-01

Polygalacturonases (EC 3.2.1.15) catalyze the random hydrolysis of 1, 4-alpha-D-galactosiduronic linkages in pectate and other galacturonans. Xylella fastidiosa possesses a single polygalacturonase gene, pglA (PD1485), and X. fastidiosa mutants deficient in the production of polygalacturonase are non-pathogenic and show a compromised ability to systemically infect grapevines. These results suggested that grapevines expressing sufficient amounts of an inhibitor of X. fastidiosa polygalacturonase might be protected from disease. Previous work in our laboratory and others have tried without success to produce soluble active X. fastidiosa polygalacturonase for use in inhibition assays. In this study, we created two enzymatically active X. fastidiosa / A. vitis polygalacturonase chimeras, AX1A and AX2A to explore the functionality of X. fastidiosa polygalacturonase in vitro. The AX1A chimera was constructed to specifically test if recombinant chimeric protein, produced in Escherichia coli, is soluble and if the X. fastidiosa polygalacturonase catalytic amino acids are able to hydrolyze polygalacturonic acid. The AX2A chimera was constructed to evaluate the ability of a unique QMK motif of X. fastidiosa polygalacturonase, most polygalacturonases have a R(I/L)K motif, to bind to and allow the hydrolysis of polygalacturonic acid. Furthermore, the AX2A chimera was also used to explore what effect modification of the QMK motif of X. fastidiosa polygalacturonase to a conserved RIK motif has on enzymatic activity. These experiments showed that both the AX1A and AX2A polygalacturonase chimeras were soluble and able to hydrolyze the polygalacturonic acid substrate. Additionally, the modification of the QMK motif to the conserved RIK motif eliminated hydrolytic activity, suggesting that the QMK motif is important for the activity of X. fastidiosa polygalacturonase. This result suggests X. fastidiosa polygalacturonase may preferentially hydrolyze a different pectic substrate or, alternatively, it has a different mechanism of substrate binding than other polygalacturonases characterized to date. PMID:26571265

Insights into the Activity and Substrate Binding of Xylella fastidiosa Polygalacturonase by Modification of a Unique QMK Amino Acid Motif Using Protein Chimeras.

PubMed

Warren, Jeremy G; Lincoln, James E; Kirkpatrick, Bruce C

2015-01-01

Polygalacturonases (EC 3.2.1.15) catalyze the random hydrolysis of 1, 4-alpha-D-galactosiduronic linkages in pectate and other galacturonans. Xylella fastidiosa possesses a single polygalacturonase gene, pglA (PD1485), and X. fastidiosa mutants deficient in the production of polygalacturonase are non-pathogenic and show a compromised ability to systemically infect grapevines. These results suggested that grapevines expressing sufficient amounts of an inhibitor of X. fastidiosa polygalacturonase might be protected from disease. Previous work in our laboratory and others have tried without success to produce soluble active X. fastidiosa polygalacturonase for use in inhibition assays. In this study, we created two enzymatically active X. fastidiosa / A. vitis polygalacturonase chimeras, AX1A and AX2A to explore the functionality of X. fastidiosa polygalacturonase in vitro. The AX1A chimera was constructed to specifically test if recombinant chimeric protein, produced in Escherichia coli, is soluble and if the X. fastidiosa polygalacturonase catalytic amino acids are able to hydrolyze polygalacturonic acid. The AX2A chimera was constructed to evaluate the ability of a unique QMK motif of X. fastidiosa polygalacturonase, most polygalacturonases have a R(I/L)K motif, to bind to and allow the hydrolysis of polygalacturonic acid. Furthermore, the AX2A chimera was also used to explore what effect modification of the QMK motif of X. fastidiosa polygalacturonase to a conserved RIK motif has on enzymatic activity. These experiments showed that both the AX1A and AX2A polygalacturonase chimeras were soluble and able to hydrolyze the polygalacturonic acid substrate. Additionally, the modification of the QMK motif to the conserved RIK motif eliminated hydrolytic activity, suggesting that the QMK motif is important for the activity of X. fastidiosa polygalacturonase. This result suggests X. fastidiosa polygalacturonase may preferentially hydrolyze a different pectic substrate or, alternatively, it has a different mechanism of substrate binding than other polygalacturonases characterized to date.

Persistence of γ-H2AX and 53BP1 foci in proliferating and non-proliferating human mammary epithelial cells after exposure to γ-rays or iron ions.

PubMed

Groesser, Torsten; Chang, Hang; Fontenay, Gerald; Chen, James; Costes, Sylvain V; Helen Barcellos-Hoff, Mary; Parvin, Bahram; Rydberg, Bjorn

2011-07-01

To investigate γ-H2AX (phosphorylated histone H2AX) and 53BP1 (tumour protein 53 binding protein No. 1) foci formation and removal in proliferating and non-proliferating human mammary epithelial cells (HMEC) after exposure to sparsely and densely ionising radiation under different cell culture conditions. HMEC cells were grown either as monolayers (2D) or in extracellular matrix to allow the formation of acinar structures in vitro (3D). Foci numbers were quantified by image analysis at various time points after exposure. Our results reveal that in non-proliferating cells under 2D and 3D cell culture conditions, iron-ion induced γ-H2AX foci were still present at 72 h after exposure, although 53BP1 foci returned to control levels at 48 h. In contrast in proliferating HMEC, both γ-H2AX and 53BP1 foci decreased to control levels during the 24-48 h time interval after irradiation under 2D conditions. Foci numbers decreased faster after γ-ray irradiation and returned to control levels by 12 h regardless of marker, cell proliferation status, and cell culture condition. The disappearance of radiation-induced γ-H2AX and 53BP1 foci in HMEC has different dynamics that depend on radiation quality and proliferation status. Notably, the general patterns do not depend on the cell culture condition (2D versus 3D). We speculate that the persistent γ-H2AX foci in iron-ion irradiated non-proliferating cells could be due to limited availability of double-strand break (DSB) repair pathways in G0/G1-phase, or that repair of complex DSB requires replication or chromatin remodelling.

Models of Shelter Management Training and Delivery Systems.

DTIC Science & Technology

1980-05-31

case study can be pre- sented orally, in writing, through a dramatization, or on film. Advantages: the case can be designed to focus on a problem or...develop a good, complex case study ; it may not be possible to use a case with more than one group (Ax & Kohls, 1977; Bauman, 1977; U.S. Civil Service...Although public information on self-protection continued to be distributed, the shelter program remained incomplete (e.g., an AIR study in 1966 noted that

Visualisation of γH2AX Foci Caused by Heavy Ion Particle Traversal; Distinction between Core Track versus Non-Track Damage

PubMed Central

Nakajima, Nakako Izumi; Brunton, Holly; Watanabe, Ritsuko; Shrikhande, Amruta; Hirayama, Ryoichi; Matsufuji, Naruhiro; Fujimori, Akira; Murakami, Takeshi; Okayasu, Ryuichi; Jeggo, Penny; Shibata, Atsushi

2013-01-01

Heavy particle irradiation produces complex DNA double strand breaks (DSBs) which can arise from primary ionisation events within the particle trajectory. Additionally, secondary electrons, termed delta-electrons, which have a range of distributions can create low linear energy transfer (LET) damage within but also distant from the track. DNA damage by delta-electrons distant from the track has not previously been carefully characterised. Using imaging with deconvolution, we show that at 8 hours after exposure to Fe (∼200 keV/µm) ions, γH2AX foci forming at DSBs within the particle track are large and encompass multiple smaller and closely localised foci, which we designate as clustered γH2AX foci. These foci are repaired with slow kinetics by DNA non-homologous end-joining (NHEJ) in G1 phase with the magnitude of complexity diminishing with time. These clustered foci (containing 10 or more individual foci) represent a signature of DSBs caused by high LET heavy particle radiation. We also identified simple γH2AX foci distant from the track, which resemble those arising after X-ray exposure, which we attribute to low LET delta-electron induced DSBs. They are rapidly repaired by NHEJ. Clustered γH2AX foci induced by heavy particle radiation cause prolonged checkpoint arrest compared to simple γH2AX foci following X-irradiation. However, mitotic entry was observed when ∼10 clustered foci remain. Thus, cells can progress into mitosis with multiple clusters of DSBs following the traversal of a heavy particle. PMID:23967070

Involvement of ROS-p38-H2AX axis in novel curcumin analogues-induced apoptosis in breast cancer cells.

PubMed

Dong, Yinhui; Yin, Shutao; Song, Xinhua; Huo, Yazhen; Fan, Lihong; Ye, Min; Hu, Hongbo

2016-04-01

Curcumin-based structural modification for developing more effective curcumin analogues has been drawning increasing attention. As alternative approach, using LC/MS guided purification, we previously obtained a series of novel natural terpene-conjugated curcuminoids from turmeric, and some of them exhibited even more potent anti-cancer activity against multiple types of cancer cells than curcumin. The purpose of this follow-up study was designed to decipher the mechanisms involved in anti-cancer activity of these novel curcumin analogues. Apoptosis was evaluated using sub-G1 analysis by flow cytometry and Cell Death ELISA Kit. Changes of protein expression were analyzed by western blotting. RNA interference was employed to inhibit expression of specific protein. We found that bisabolocurcumin ether (T1) and demethoxybisabolocurcumin ether (T2) were able to trigger much stronger apoptosis induction in multiple types of cancer cells than curcumin, which was attributed to persistent and stronger ROS generation. ROS induction by T1 resulted in activation of p38/H2AX axis and p53. Inhibition of p38/H2AX led to a significant reduction of apoptosis, whereas inactivation of p53 caused a dramatically enhanced H2AX phosphorylation and apoptosis induction, suggesting activation of p38/H2AX contributed to apoptosis induction by T1, whereas p53 activation protected novel curcumins-induced apoptosis via suppression of H2AX activation. Our findings provide mechanistic support for the potential use of terpene-conjugated curcuminoids as a novel class of cancer chemopreventive agents. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Soluble arabinoxylan enhances large intestinal microbial health biomarkers in pigs fed a red meat-containing diet.

PubMed

Williams, Barbara A; Zhang, Dagong; Lisle, Allan T; Mikkelsen, Deirdre; McSweeney, Christopher S; Kang, Seungha; Bryden, Wayne L; Gidley, Michael J

2016-04-01

The aim of this study was to investigate how moderately increased dietary red meat combined with a soluble fiber (wheat arabinoxylan [AX]) alters the large intestinal microbiota in terms of fermentative end products and microbial community profiles in pigs. Four groups of 10 pigs were fed Western-type diets containing two amounts of red meat, with or without a solubilized wheat AX-rich fraction for 4 wk. After euthanasia, fermentative end products (short-chain fatty acids, ammonia) of digesta from four sections of large intestine were measured. Di-amino-pimelic acid was a measure of total microbial biomass, and bacterial profiles were determined using a phylogenetic microarray. A factorial model determined effects of AX and meat content. Arabinoxylan was highly fermentable in the cecum, as indicated by increased concentrations of short-chain fatty acids (particularly propionate). Protein fermentation end products were decreased, as indicated by the reduced ammonia and branched-chain ratio although this effect was less prominent distally. Microbial profiles in the distal large intestine differed in the presence of AX (including promotion of Faecalibacterium prausnitzii), consistent with an increase in carbohydrate versus protein fermentation. Increased di-amino-pimelic acid (P < 0.0001) suggested increased microbial biomass for animals fed AX. Solubilized wheat AX has the potential to counteract the effects of dietary red meat by reducing protein fermentation and its resultant toxic end products such as ammonia, as well as leading to a positive shift in fermentation end products and microbial profiles in the large intestine. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

TU-H-CAMPUS-TeP3-01: Gold Nanoparticle-Enhanced Radiation Therapy in In Vitro A549 Lung Carcinoma: Studies in Both Traditional Monolayer and Three Dimensional Cell Culture Models

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

Oumano, M; University of Massachusetts Lowell, Lowell, MA; Ngwa, W

Purpose: To measure the increase in in vitro radiosensitivity for A549 lung carcinoma cells due to gold nanoparticle (GNP) radiation dose enhancement in both traditional monolayer and three dimensional (3D) cell culture models. Methods: A γH2AX immunofluorescence assay is performed on monolayer A549 cell culture and quantitatively analyzed to measure the increase in double strand breaks (DSBs) resulting from GNP dose enhancement. A clonogenic survival assay (CSA) is then performed on monolayer A549 cell culture to assess true viability after treatment. And lastly, another γH2AX assay is performed on 3D A549 multicellular nodules overlaid on a bed of growth factormore » reduced matrigel to measure dose response in a model that better recapitulates treatment response to actual tumors in vivo. Results: The first γH2AX assay performed on the monolayer cell culture shows a significant increase in DSBs due to GNP dose enhancement. The maximum average observed increase in normalized fluorescent intensity for monolayer cell culture is 171% for the 6Gy-treatment groups incubated in 0.556 mg Au/ml solution. The CSA performed on monolayer cell culture also shows considerable GNP dose enhancement. The maximum decrease in the normalized surviving fraction is 12% for the 4Gy-treatment group incubated in 0.556 mg Au/ml. And lastly, the GNP dose enhancement is confirmed to be mitigated in three dimensional cell culture models as compared to the traditional monolayer model. The maximum average observed dose enhancement for 3D cell culture is 19% for the 6Gy-treatment groups and incubated in 0.556 mg Au/ml. Conclusion: A marked increase in radiosensitivity is observed for A549 lung carcinoma cells when treated with GNPs plus radiation as opposed to radiation alone. Traditional monolayer cell culture also shows a much more pronounced radiation dose enhancement than 3D cell culture.« less

DNA DSB measurements and modelling approaches based on gamma-H2AX foci time evolution

NASA Astrophysics Data System (ADS)

Esposito, Giuseppe; Campa, Alessandro; Antonelli, Francesca; Mariotti, Luca; Belli, Mauro; Giardullo, Paola; Simone, Giustina; Antonella Tabocchini, Maria; Ottolenghi, Andrea

DNA double strand breaks (DSBs) induced by ionising radiation are considered the main dam-age related to the deleterious consequences in the cells. Unrepaired or mis-repaired DSBs can cause mutations or loss of chromosome regions which can eventually lead to cell death or neo-plastic transformation. Quantification of the number and complexity of DSBs induced by low doses of radiation remains a complex problem. About ten years ago Rogakou et al. proposed an immunofluorescent technique able to detect even a single DSB per cell. This approach is based on the serine 139 phosphorylation of many molecules (up to 2000) of histone H2AX (γg-H2AX) following the induction of a DSB in the DNA. DSB can be visualized as foci by immunofluores-cence by using phospho-specific antibodies, so that enumeration of foci can be used to measure DSB induction and processing. It is still not completely clear how γ-H2AX dephosphorylation takes place; however it has been related with DSB repair, in particular with the efficiency of DSB repair. In this work we analyse the H2AX phosphorylation-dephosphorylation kinetics after irradiation of primary human fibroblasts (AG1522 cell line) with radiation of differing quality, that is γ-rays and α-particles (125 keV/µm), with the aim of comparing the time evolution of γ-H2AX foci. Our results show that, after a dose of 0.5 Gy, both γ-rays and α-particles induce the maximum number of γ-H2AX foci within 30 minutes from irradiation, that this number depends on the radiation type and is consistent with the number of track traversal in α-irradiated nuclei, that the dephosphorylation kinetics are very different, being the α-induced foci rate of disappearence slower than that of γ-induced foci. In this work a modellistic approach to estimate the number of DSB induced by γ-rays detectable by using the γ-H2AX assay is presented. The competing processes of appearance and disappearance of visible foci will be modeled taking into account the phosphorylation and dephosphorylation phenomena. The effect of possible overlapping DSB induced at short distance (within 2 Mbp) will be also taken into account. Moreover, for charged particles (in particular for α-particles) the average number of DSB per focus is calculated.

Anti-CD74 antibodies have no diagnostic value in early axial spondyloarthritis: data from the spondyloarthritis caught early (SPACE) cohort.

PubMed

de Winter, Janneke J; van de Sande, Marleen G; Baerlecken, Niklas; Berg, Inger; Ramonda, Roberta; van der Heijde, Désirée; van Gaalen, Floris A; Witte, Torsten; Baeten, Dominique L

2018-03-01

Anti-CD74 IgG antibodies are reported to be elevated in patients with axial spondyloarthritis (axSpA). This study assessed the diagnostic value of anti-CD74 antibodies in patients with early axSpA. Anti-CD74 IgG and IgA antibodies were first measured in an exploratory cohort of patients with radiographic axSpA (138 patients with ankylosing spondyloarthritis (AS)) and 57 healthy controls and then were measured in patients with early axSpA (n = 274) and with non-SpA chronic back pain (CBP) (n = 319), participating in the spondyloarthritis caught early (SPACE) prospective cohort study of patients under 45 years old with early back pain (for ≥ 3 months, but ≤ 2 years). In the exploratory cohort, anti-CD74 IgG antibodies were present in 79.7% of patients with AS vs. 43.9% of healthy controls (p < 0.001). Anti-CD74 IgA antibodies were present in 28.5% of patients with AS vs. 5.3% of healthy controls (p < 0.001). In the SPACE cohort, anti-CD74 IgG antibody levels were present in 46.4% of the patients with axSpA vs. 47.9% of the patients with CBP (p = 0.71). Anti-CD74 IgA antibodies were present in 54.7% of the patients with axSpA and 37.0% of the patients with CBP (p < 0.001). This resulted in a positive predictive value of 58.8% (compared to a prior probability of 46.2%) and a negative predictive value of 59.1% (compared to a prior probability of 53.8%). In a regression model, total serum IgA was associated with axSpA odds ratio (OR) 1.19, p < 0.001) whereas anti-CD74 IgA was not (OR) 1.01, p = 0.33). Furthermore, anti-CD74 IgA was associated with sacroiliitis on magnetic resonance imaging (MRI) (OR) = 2.50, p = 0.005) and heel enthesitis (OR) = 2.56, p = 0.002). Albeit anti-CD74 IgA is elevated in patients with early axSpA, this elevation is not sufficiently specific to yield significant diagnostic value in patients under 45 years old presenting with early back pain.

Curved Saccade Trajectories Reveal Conflicting Predictions in Associative Learning

ERIC Educational Resources Information Center

Koenig, Stephan; Lachnit, Harald

2011-01-01

We report how the trajectories of saccadic eye movements are affected by memory interference acquired during associative learning. Human participants learned to perform saccadic choice responses based on the presentation of arbitrary central cues A, B, AC, BC, AX, BY, X, and Y that were trained to predict the appearance of a peripheral target…

Repression of Multiple Myeloma Growth and Preservation of Bone with Combined Radiotherapy and Anti-angiogenic Agent

PubMed Central

Jia, Dan; Koonce, Nathan A.; Halakatti, Roopa; Li, Xin; Yaccoby, Shmuel; Swain, Frances L.; Suva, Larry J.; Hennings, Leah; Berridge, Marc S.; Apana, Scott M.; Mayo, Kevin; Corry, Peter M.; Griffin, Robert J.

2011-01-01

The effects of ionizing radiation, with or without the antiangiogenic agent anginex (Ax), on multiple myeloma growth were tested in a SCID-rab mouse model. Mice carrying human multiple myeloma cell-containing pre-implanted bone grafts were treated weekly with various regimens for 8 weeks. Rapid multiple myeloma growth, assessed by bioluminescence intensity (IVIS), human lambda Ig light chain level in serum (ELISA), and the volume of bone grafts (caliper), was observed in untreated mice. Tumor burden in mice receiving combined therapy was reduced to 59% (by caliper), 43% (by ELISA), and 2% (by IVIS) of baseline values after 8 weeks of treatment. Ax or radiation alone slowed but did not stop tumor growth. Four weeks after the withdrawal of the treatments, tumor burden remained minimal in mice given Ax + radiation but increased noticeably in the other three groups. Multiple myeloma suppression by Ax + radiation was accompanied by a marked decrease in the number and activity of osteoclasts in bone grafts assessed by histology. Bone graft integrity was preserved by Ax + radiation but was lost in the other three groups, as assessed by microCT imaging and radiography. These results suggest that radiotherapy, when primed by anti-angiogenic agents, may be a potent therapy for focal multiple myeloma. PMID:20518660

Mode of action of family 10 and 11 endoxylanases on water-unextractable arabinoxylan.

PubMed

Vardakou, Maria; Katapodis, Petros; Samiotaki, Martina; Kekos, Dimitris; Panayotou, George; Christakopoulos, Paul

2003-11-01

Microbial endo-beta-1,4-xylanases (EXs, EC 3.2.1.8) belonging to glycanase families 10 and 11 differ in their action on water-unextractable arabinoxylan (WU-AX). WU-AX was incubated with different levels of a Thermoascus aurantiacus family 10 and a Sporotrichum thermophile family 11 endoxylanases. At 10 g l(-1) arabinoxylan, enzyme concentrations (KE values) needed to obtain half-maximal hydrolysis rates (V(max) values) were 4.4 nM for the xylanase from T. aurantiacus and 7.1 nM for the xylanase from S. thermophile. Determination of Vmax/KE revealed that the family 10 enzyme hydrolysed two times more efficiently WU-AX than the family 11 enzyme. Molecular weights of the products formed were assessed and separation of feruloyl-oligosaccharides was achieved by anion-exchange and size-exclusion chromatography (SEC). The main difference between the feruloylated products by xylanases of family 10 and 11 concerned the length of the products containing feruloyl-arabinosyl substitution. The xylanase from T. aurantiacus liberated from WU-AX a feruloyl arabinoxylodisaccharide (FAX2) as the shortest feruloylated fragment in contrast with the enzyme from S. thermophile, which liberated a feruloyl arabinoxylotrisaccharide (FAX3). These results indicated that different factors govern WU-AX breakdown by the two endoxylanases.

Between-monitor differences in step counts are related to body size: implications for objective physical activity measurement.

PubMed

Pomeroy, Jeremy; Brage, Søren; Curtis, Jeffrey M; Swan, Pamela D; Knowler, William C; Franks, Paul W

2011-04-27

The quantification of the relationships between walking and health requires that walking is measured accurately. We correlated different measures of step accumulation to body size, overall physical activity level, and glucose regulation. Participants were 25 men and 25 women American Indians without diabetes (Age: 20-34 years) in Phoenix, Arizona, USA. We assessed steps/day during 7 days of free living, simultaneously with three different monitors (Accusplit-AX120, MTI-ActiGraph, and Dynastream-AMP). We assessed total physical activity during free-living with doubly labeled water combined with resting metabolic rate measured by expired gas indirect calorimetry. Glucose tolerance was determined during an oral glucose tolerance test. Based on observed counts in the laboratory, the AMP was the most accurate device, followed by the MTI and the AX120, respectively. The estimated energy cost of 1000 steps per day was lower in the AX120 than the MTI or AMP. The correlation between AX120-assessed steps/day and waist circumference was significantly higher than the correlation between AMP steps and waist circumference. The difference in steps per day between the AX120 and both the AMP and the MTI were significantly related to waist circumference. Between-monitor differences in step counts influence the observed relationship between walking and obesity-related traits.

Immunofluorescent Detection of DNA Double Strand Breaks induced by High-LET Radiation

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Wu, Honglu; Desai, Nirav

2004-01-01

Within cell nuclei, traversing charged heavy ion particles lead to the accumulation of proteins related to DNA lesions and repair along the ion trajectories. Irradiation using a standard geometric setup with the beam path perpendicular to the cell monolayer generates discrete foci of several proteins known to localize at sites of DNA double strand breaks (DSBs). One such molecule is the histone protein H2AX (gamma-H2AX), which gets rapidly phosphorylated in response to ionizing radiation. Here we present data obtained with a modified irradiation geometry characterized by a beam path parallel to a monolayer of human fibroblast cells. This new irradiation geometry leads to the formation of gamma-H2AX aggregates in the shape of streaks stretching over several micrometers in the x/y plane, thus enabling the analysis of the fluorescence distributions along the particle trajectories. Qualitative analysis of these distributions presented insights into the DNA repair kinetics along the primary track structure and visualization of possible chromatin movement. We also present evidence of colocalization of gamma-H2AX with several other proteins in responses to ionizing radiation exposure. Analysis of gamma-H2AX has the potential to provide useful information on human cell responses to high LET radiation after exposure to space-like radiation.

Long-Standing Motor and Sensory Recovery following Acute Fibrin Sealant Based Neonatal Sciatic Nerve Repair

PubMed Central

Ferreira Junior, Rui Seabra

2016-01-01

Brachial plexus lesion results in loss of motor and sensory function, being more harmful in the neonate. Therefore, this study evaluated neuroprotection and regeneration after neonatal peripheral nerve coaptation with fibrin sealant. Thus, P2 neonatal Lewis rats were divided into three groups: AX: sciatic nerve axotomy (SNA) without treatment; AX+FS: SNA followed by end-to-end coaptation with fibrin sealant derived from snake venom; AX+CFS: SNA followed by end-to-end coaptation with commercial fibrin sealant. Results were analyzed 4, 8, and 12 weeks after lesion. Astrogliosis, microglial reaction, and synapse preservation were evaluated by immunohistochemistry. Neuronal survival, axonal regeneration, and ultrastructural changes at ventral spinal cord were also investigated. Sensory-motor recovery was behaviorally studied. Coaptation preserved synaptic covering on lesioned motoneurons and led to neuronal survival. Reactive gliosis and microglial reaction decreased in the same groups (AX+FS, AX+CFS) at 4 weeks. Regarding axonal regeneration, coaptation allowed recovery of greater number of myelinated fibers, with improved morphometric parameters. Preservation of inhibitory synaptic terminals was accompanied by significant improvement in the motor as well as in the nociceptive recovery. Overall, the present data suggest that acute repair of neonatal peripheral nerves with fibrin sealant results in neuroprotection and regeneration of motor and sensory axons. PMID:27446617

Sirt1 physically interacts with Tip60 and negatively regulates Tip60-mediated acetylation of H2AX

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

Yamagata, Kazutsune, E-mail: kyamagat@ncc.go.jp; Kitabayashi, Issay

2009-12-25

Sirt1 appear to be NAD(+)-dependent deacetylase that deacetylates histones and several non-histone proteins. In this study, we identified Sirt1 as a physical interaction partner of Tip60, which is a mammalian MYST-type histone acetyl-transferase that specifically acetylates histones H2A and H4. Although Tip60 also acetylates DNA damage-specific histone H2A variant H2AX in response to DNA damage, which is a process required for appropriate DNA damage response, overexpression of Sirt1 represses Tip60-mediated acetylation of H2AX. Furthermore, Sirt1 depletion by RNAi causes excessive acetylation of H2AX, and enhances accumulation of {gamma}-ray irradiation-induced MDC1, BRCA1, and Rad51 foci in nuclei. These findings suggest thatmore » Sirt1 functions as negative regulator of Tip60-mediated acetylation of H2AX. Moreover, Sirt1 deacetylates an acetylated Tip60 in response to DNA damage and stimulates proteasome-dependent Tip60 degradation in vivo, suggesting that Sirt1 negatively regulates the protein level of Tip60 in vivo. Sirt1 may thus repress excessive activation of the DNA damage response and Rad51-homologous recombination repair by suppressing the function of Tip60.« less

HLA B27 antigen in Middle Eastern and Arab countries: systematic review of the strength of association with axial spondyloarthritis and methodological gaps.

PubMed

Ziade, Nelly Raymond

2017-06-29

Axial spondyloarthritis (AxSpA) is a relatively frequent and debilitating disease, with a prevalence ranging from 0.1 to 2% in the Caucasian population. Current Assessment of Spondyloarthritis International Society (ASAS) classification criteria of AxSpA rely either on sacroiliitis on imaging plus one SpA feature or positive HLAB27 antigen plus two SpA features, in a patient with chronic low back pain and age at onset of less than 45 years. Therefore, HLA-B27 is a central feature in SpA classification and plays a pivotal role in referral strategies and early diagnosis. The primary objective of the study is to review the prevalence of HLA-B27 in normal and AxSpA populations in Middle Eastern and Arab Countries and to assess the strength of association between HLA-B27 antigen and AxSpA. The secondary objective is to identify the gaps in the methodology of the studies and suggest a framework for future research. Studies were included in the analysis if they reported prevalence of HLA-B27 in AxSpA and/or general population and if they covered geographical location in the Middle East or Arab countries in the Mediterranean basin. Odds ratios (OR) were calculated for each country, as a measure of the strength of association between HLA-B27 and AxSpA, compared to the normal population, using the two-by-two frequency table. Available data from the literature were analyzed according to the following quality indicators: sample size, method of HLA-B27 testing, presence of control group and external validity. Twenty-seven studies were analyzed. HLAB27 prevalence in the normal population ranged from 0.3% (Oman) to 6.8% (Turkey). HLA-B27 prevalence in AxSpA ranged from 26.2% (Lebanon) to 91% (Turkey). HLA-B27 prevalence in all SpA ranged from 13.87% (Lebanon) to 69.43% (Kuwait). Peripheral SpA was less associated with HLA-B27 than AxSpA, indicating the need of differentiating between the two entities when calculating prevalence. When available (8 studies), the OR ranged from 21.63 (Morocco) to 105.6 (Syria). The high heterogeneity between the results can be due to differences in methodology: study sample size, different classification criteria, absence of control groups, HLA-B27 testing method. The prevalence of HLA-B27 in the normal population is significantly lower in the Middle Eastern and Arab countries than in Western Countries. However, HLA-B27 testing can be useful for AxSpA positive diagnosis, given the high OR. Heterogeneity between countries may be due to methodological differences.

Distinct kinetics of DNA repair protein accumulation at DNA lesions and cell cycle-dependent formation of γH2AX- and NBS1-positive repair foci.

PubMed

Suchánková, Jana; Kozubek, Stanislav; Legartová, Soňa; Sehnalová, Petra; Küntziger, Thomas; Bártová, Eva

2015-12-01

The DNA damage response is a fundamental, well-regulated process that occurs in the genome to recognise DNA lesions. Here, we studied kinetics of proteins involved in DNA repair pathways and their recruitment to DNA lesions during the cell cycle. In non-irradiated and irradiated cells, we analysed the distribution pattern and spatiotemporal dynamics of γH2AX, 53BP1, BMI1, MDC1, NBS1, PCNA, coilin and BRCA1 proteins. We observed that spontaneous and irradiation-induced foci (IRIF) demonstrated a high abundance of phosphorylated H2AX, which was consistent with 53BP1 and BMI1 protein accumulation. However, NBS1 and MDC1 proteins were recruited to nuclear bodies (NBs) to a lesser extent. Irradiation by γ-rays significantly increased the number of 53BP1- and γH2AX-positive IRIF, but cell cycle-dependent differences were only observed for γH2AX-positive foci in both non-irradiated and γ-irradiated cells. In non-irradiated cells, the G2 phase was characterised by an increased number of spontaneous γH2AX-foci; this increase was more pronounced after γ-irradiation. Cells in G2 phase had the highest number of γH2AX-positive foci. Similarly, γ-irradiation increased the number of NBS1-positive NBs only in G2 phase. Moreover, NBS1 accumulated in nucleoli after γ-irradiation showed the slowest recovery after photobleaching. Analysis of protein accumulation kinetics at locally induced DNA lesions showed that in HeLa cells, BMI1, PCNA and coilin were rapidly recruited to the lesions, 10-15 s after UVA-irradiation, whereas among the other proteins studied, BRCA1 demonstrated the slowest recruitment: BRCA1 appeared at the lesion 20 min after local micro-irradiation by UVA laser. We show that the kinetics of the accumulation of selected DNA repair-related proteins is protein specific at locally induced DNA lesions, and that the formation of γH2AX- and NBS1-positive foci, but not 53BP1-positive NBs, is cell cycle dependent in HeLa cells. Moreover, γH2AX is the most striking protein present not only at DNA lesions, but also spreading out in their vicinity. Our conclusions highlight the significant role of the spatiotemporal dynamics of DNA repair-related proteins and their specific assembly/disassembly at DNA lesions, which can be cell type- and cell cycle dependent. © 2015 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

In Barrett's esophagus patients and Barrett's cell lines, ursodeoxycholic acid increases antioxidant expression and prevents DNA damage by bile acids.

PubMed

Peng, Sui; Huo, Xiaofang; Rezaei, Davood; Zhang, Qiuyang; Zhang, Xi; Yu, Chunhua; Asanuma, Kiyotaka; Cheng, Edaire; Pham, Thai H; Wang, David H; Chen, Minhu; Souza, Rhonda F; Spechler, Stuart Jon

2014-07-15

Hydrophobic bile acids like deoxycholic acid (DCA), which cause oxidative DNA damage and activate NF-κB in Barrett's metaplasia, might contribute to carcinogenesis in Barrett's esophagus. We have explored mechanisms whereby ursodeoxycholic acid (UDCA, a hydrophilic bile acid) protects against DCA-induced injury in vivo in patients and in vitro using nonneoplastic, telomerase-immortalized Barrett's cell lines. We took biopsies of Barrett's esophagus from 21 patients before and after esophageal perfusion with DCA (250 μM) at baseline and after 8 wk of oral UDCA treatment. DNA damage was assessed by phospho-H2AX expression, neutral CometAssay, and phospho-H2AX nuclear foci formation. Quantitative PCR was performed for antioxidants including catalase and GPX1. Nrf2, catalase, and GPX1 were knocked down with siRNAs. Reporter assays were performed using a plasmid construct containing antioxidant responsive element. In patients, baseline esophageal perfusion with DCA significantly increased phospho-H2AX and phospho-p65 in Barrett's metaplasia. Oral UDCA increased GPX1 and catalase levels in Barrett's metaplasia and prevented DCA perfusion from inducing DNA damage and NF-κB activation. In cells, DCA-induced DNA damage and NF-κB activation was prevented by 24-h pretreatment with UDCA, but not by mixing UDCA with DCA. UDCA activated Nrf2 signaling to increase GPX1 and catalase expression, and protective effects of UDCA pretreatment were blocked by siRNA knockdown of these antioxidants. UDCA increases expression of antioxidants that prevent toxic bile acids from causing DNA damage and NF-κB activation in Barrett's metaplasia. Elucidation of this molecular pathway for UDCA protection provides rationale for clinical trials on UDCA for chemoprevention in Barrett's esophagus. Copyright © 2014 the American Physiological Society.

In Barrett's esophagus patients and Barrett's cell lines, ursodeoxycholic acid increases antioxidant expression and prevents DNA damage by bile acids

PubMed Central

Peng, Sui; Huo, Xiaofang; Rezaei, Davood; Zhang, Qiuyang; Zhang, Xi; Yu, Chunhua; Asanuma, Kiyotaka; Cheng, Edaire; Pham, Thai H.; Wang, David H.; Chen, Minhu; Spechler, Stuart Jon

2014-01-01

Hydrophobic bile acids like deoxycholic acid (DCA), which cause oxidative DNA damage and activate NF-κB in Barrett's metaplasia, might contribute to carcinogenesis in Barrett's esophagus. We have explored mechanisms whereby ursodeoxycholic acid (UDCA, a hydrophilic bile acid) protects against DCA-induced injury in vivo in patients and in vitro using nonneoplastic, telomerase-immortalized Barrett's cell lines. We took biopsies of Barrett's esophagus from 21 patients before and after esophageal perfusion with DCA (250 μM) at baseline and after 8 wk of oral UDCA treatment. DNA damage was assessed by phospho-H2AX expression, neutral CometAssay, and phospho-H2AX nuclear foci formation. Quantitative PCR was performed for antioxidants including catalase and GPX1. Nrf2, catalase, and GPX1 were knocked down with siRNAs. Reporter assays were performed using a plasmid construct containing antioxidant responsive element. In patients, baseline esophageal perfusion with DCA significantly increased phospho-H2AX and phospho-p65 in Barrett's metaplasia. Oral UDCA increased GPX1 and catalase levels in Barrett's metaplasia and prevented DCA perfusion from inducing DNA damage and NF-κB activation. In cells, DCA-induced DNA damage and NF-κB activation was prevented by 24-h pretreatment with UDCA, but not by mixing UDCA with DCA. UDCA activated Nrf2 signaling to increase GPX1 and catalase expression, and protective effects of UDCA pretreatment were blocked by siRNA knockdown of these antioxidants. UDCA increases expression of antioxidants that prevent toxic bile acids from causing DNA damage and NF-κB activation in Barrett's metaplasia. Elucidation of this molecular pathway for UDCA protection provides rationale for clinical trials on UDCA for chemoprevention in Barrett's esophagus. PMID:24852569

Practice Patterns of Radiation Field Design for Sentinel Lymph Node-Positive Early-Stage Breast Cancer.

PubMed

Azghadi, Soheila; Daly, Megan; Mayadev, Jyoti

2016-10-01

Recent randomized trials have led to decreased use of completion axillary lymph node dissection (ALND) in early-stage breast cancer patients with a positive sentinel lymph node (SLN), causing controversy surrounding radiotherapy coverage of the axilla. We investigated the practice variation among radiation oncologists for regional nodal coverage for clinicopathologic scenarios and evaluated axillary field design decision-making processes. A customized, web-based questionnaire was e-mailed to 983 community (n = 617) and academic (n = 366) radiation oncologists with a breast cancer subspecialty practicing in the United States. The survey consisted of 18 multiple-choice questions evaluating general clinical preferences surrounding radiation therapy (RT) field design for patients with early-stage breast cancer and a positive SLN. Seven case scenarios were developed to investigate the field design in the setting of specific clinical and pathologic risk factors. Nodal coverage was classified as standard tangents (STs), high tangents (HTs), STs and a supraclavicular field (SCF), or STs and full axillary coverage (AX). A total of 145 evaluable responses were collected, with a response rate of 15.0%. Of the respondents, 12 (8.3%) reported using completion ALND for patients with 1 to 3 positive SLNs without extracapsular extension (ECE) and 66 (45.5%) performed ALND with 1 to 3 positive SLNs with ECE. For micrometastatic SLNs, with no lymphovascular system invasion, 115 (87.1%) used STs or HTs. The use of neoadjuvant chemotherapy (NAC) influenced RT field design for patients with a positive SLN without ECE, with 64 (48.5%) using STs and SCF or STs and AX treatment without NAC and 94 (70.7%) using SCF and AX after NAC. With macrometastatic SLN involvement, most respondents preferred SCF (45.27%) and AX (45.66%). In contrast, for micrometastatic involvement, HTs (43.61%) were frequently chosen. Forty (27.8%) reported using online predictive nomograms to predict further axillary involvement, with no difference between the academic and community radiation oncologists (P = .11). In SLN biopsy-positive early-stage breast cancer with omission of completion ALND, axillary RT is increasing used to cover the undissected axilla. Most respondents use SCF or AX for patients with low to intermediate pathologic features. Online prediction nomograms are used by a few practitioners to assist in clinical decision-making in this setting. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of genotoxicity related to oral methylene blue chromoendoscopy.

PubMed

Repici, Alessandro; Ciscato, Camilla; Wallace, Michael; Sharma, Prateek; Anderloni, Andrea; Carrara, Silvia; Di Leo, Milena; Hassan, Cesare

2018-06-15

 An oral formulation of methylene blue with colonic delivery (MB-MMX) has been developed to increase detection of colorectal polys during colonoscopy. Traditionally, there have been safety concerns regarding DNA damage when methylene blue is exposed to white light. The aim of this study was to evaluate DNA damage in colonic mucosa after MB-MMX chromoendoscopy.  This was an open-label phase II safety study to assess for genotoxicity on colorectal biopsies of patients undergoing two sequential colonoscopies before and after an oral dose of 200 mg MB-MMX added to their bowel prep. Analysis of a biomarker of double-stranded DNA breaks, γH2AX, was performed on biopsy specimens.  Ten patients were included in the study. The mean expression of γH2AX ± 95 % confidence intervals of the 50 biopsies before and after MB-MMX administration were 0.58 ± 0.08 and 0.62 ± 0.09, respectively ( P  = 0.24). None of the analyzed samples showed excess positive γH2AX expression, confirming the absence of DNA damage on biopsies after methylene blue exposure. No deaths or serious adverse events occurred.  An oral dose of 200 mg of MB-MMX did not result in any detectable DNA damage. © Georg Thieme Verlag KG Stuttgart · New York.

Performance evaluation of candidate space suit elements for the next generation orbital EMU

NASA Technical Reports Server (NTRS)

West, Philip R.; Trausch, Stephanie V.

1992-01-01

The AX-5 all metallic, multibearing technologies developed at the Ames Research Center and the Mk III fabric and metallic technologies developed at the Johnson Space Center were evaluated using the current Space Shuttle space suit technologies as a baseline. Manned evaluations were performed in the Weightless Environment Training Facility and KC-135 zero-gravity aircraft. Joint torque, range, cycle life, and environmental protection characteristics were analyzed during unmanned tests. Both numerical results and test subject comments on performance are presented.

Reliability of a Fully Automated Interpretation of γ -H2AX Foci in Lymphocytes of Moderately Trained Subjects under Resting Conditions.

PubMed

Heydenreich, Juliane; Otto, Christoph; Mayer, Frank; Carlsohn, Anja

2014-01-01

Background. Analysis of γ-H2AX foci is a promising approach to evaluate exercise-induced DNA damage. However, baseline levels and day-to-day variability of γ-H2AX foci have not been investigated in healthy subjects at rest. Methods. Blood was taken from eight moderately trained healthy males (29 ± 3 yrs, 1.84 ± 0.03 m, and 85 ± 6 kg) at two separate days (M1/M2) after 24-hour exercise cessation. Number of γ-H2AX foci per 100 lymphocytes (N), number of foci per affected lymphocyte (NAL), percentage of affected lymphocytes (PAL), and diameter (D) of γ-H2AX foci were analyzed (mean ± SD). Differences between M1 and M2 were analyzed using paired t-tests (α = 0.05). Day-to-day variability was evaluated by calculating the coefficients of variation (CV%), bias, and limits of agreement (LoA). Results. There were no statistically significant differences between M1 (N: 7.6 ± 4.4, NAL: 1.2 ± 0.2, PAL: 5.9 ± 2.6%, and D: 0.63 ± 0.07) and M2 (N: 8.4 ± 4.6, NAL: 1.3 ± 0.1, PAL: 6.9 ± 4.2%, and D: 0.66 ± 0.06). CV was calculated to be 98.5% (N), 88.9% (PAL), 11.3% (NAL), and 8.0% (D). Bias (LoA) was 0.75 (-15.2/13.7), -0.02 (-0.36/0.33), -1.0 (-11.9/9.9), and -0.04 (-0.16/0.09), respectively. Conclusions. Background level in healthy subjects is approximately 0.07 to 0.09 γ-H2AX foci/cell. NAL and D are reliable measures.

Active B12: a rapid, automated assay for holotranscobalamin on the Abbott AxSYM analyzer.

PubMed

Brady, Jeff; Wilson, Lesley; McGregor, Lynda; Valente, Edward; Orning, Lars

2008-03-01

Conventional tests for vitamin B(12) deficiency measure total serum vitamin B12, whereas only that portion of vitamin B12 carried by transcobalamin (holotranscobalamin) is metabolically active. Measurement of holotranscobalamin (holoTC) may be more diagnostically accurate for detecting B(12) deficiency that requires therapy. We developed an automated assay for holoTC that can be used on the Abbott AxSYM immunoassay analyzer. AxSYM Active B12 is a 2-step sandwich microparticle enzyme immunoassay. In step 1, a holoTC-specific antibody immobilized onto latex microparticles captures holoTC in samples of serum or plasma. In step 2, the captured holoTC is detected with a conjugate of alkaline phosphatase and antiTC antibody. Neither apoTC nor haptocorrin exhibited detectable cross-reactivity. The detection limit was < or = 0.1 pmol/L. Within-run and total imprecision (CV ranges) were 3.4%-5.1% and 6.3%-8.5%, respectively. Assay CVs were < 20% from at least 3 pmol/L to 107 pmol/L. With diluted serum samples, measured concentrations were 104%-114% of the expected values in the working range of the assay. No interference from bilirubin, hemoglobin, triglycerides, erythrocytes, rheumatoid factor, or total protein was detected at expected (abnormal) concentrations. A comparison of the AxSYM Active B12 assay with a commercial RIA for holoTC yielded the regression equation: AxSYM = 0.98RIA + 4.7 pmol/L (S(y x), 11.4 pmol/L; n = 204). Assay throughput was 45 tests/h. A 95% reference interval of 19-134 pmol/L holoTC was established with samples from 292 healthy individuals. The AxSYM Active B12 assay allows rapid, precise, sensitive, specific, and automated measurement of human holoTC in serum and plasma.

Bifidobacterium longum D2 enhances microbial degradation of long-chain arabinoxylans in an in vitro model of the proximal colon.

PubMed

Truchado, P; Van den Abbeele, P; Rivière, A; Possemiers, S; De Vuyst, L; Van de Wiele, T

2015-01-01

Long-chain arabinoxylans (LC-AX) are degraded in the colon by intestinal bacteria possessing AX-degrading enzymes, such as bifidobacteria. Enzymatic activity of intestinal bacterial might vary depending on the composition of the gut microbiota. To compare the enzymatic activities of the bacterial gut communities of two healthy individuals (donors D1 and D2), these bacterial communities were inoculated into in vitro model M-SHIME(®). Differences in xylanase activities and denaturing gradient gel electrophoresis profiles, in particular a DNA-band corresponding with Bifidobacterium longum, were found in the proximal colon vessel. 16S rRNA gene sequencing analysis demonstrated the presence of two different B. longum species in these bacterial communities, showing 99% gene sequence similarity with B. longum NCC2705 and B. longum. subsp. longum KACC 91563, respectively, further referred to as B. longum D1 and B. longum D2. When grown on LC-AX as the sole added energy source, B. longum D2 displayed significantly higher activities of β-xylanase (5.3-fold), β-xylosidase (2.9-fold), and α-arabinofuranosidase (1.5-fold), respectively, compared to B. longum D1. When B. longum D2 was inoculated in the M-SHIME, inoculated with the bacterial gut communities of the individual with low AX-degrading enzyme activities, the β-xylanase activity increased (1.5-fold) in the proximal vessel. We demonstrated the presence of differences in LC-AX degrading enzyme activities of the bacterial gut communities of two individuals in the in vitro M-SHIME model, which could be linked to the presence of a potent AX-degrading B. longum (D2) strain.

The nuclear aryl hydocarbon receptor is involved in regulation of DNA repair and cell survival following treatment with ionizing radiation.

PubMed

Dittmann, K H; Rothmund, M C; Paasch, A; Mayer, C; Fehrenbacher, B; Schaller, M; Frauenstein, K; Fritsche, E; Haarmann-Stemmann, T; Braeuning, A; Rodemann, H P

2016-01-05

In the present study, we explored the role of the aryl hydrocarbon receptor (AhR) for γ-H2AX associated DNA repair in response to treatment with ionizing radiation. Ionizing radiation was able to stabilize AhR protein and to induce a nuclear translocation in a similar way as described for exposure to aromatic hydrocarbons. A comparable AhR protein stabilization was obtained by treatment with hydroxyl-nonenal-generated by radiation-induced lipid peroxidation. AhR knockdown resulted in significant radio-sensitization of both A549- and HaCaT cells. Under these conditions an increased amount of residual γ-H2AX foci and a delayed decline of γ-H2AX foci was observed. Knockdown of the co-activator ARNT, which is essential for transcriptional activation of AhR target genes, reduced AhR-dependent CYP1A expression in response to irradiation, but was without effect on the amount of residual γ-H2AX foci. Nuclear AhR was found in complex with γ-H2AX, DNA-PK, ATM and Lamin A. AhR and γ-H2AX form together nuclear foci, which disappear during DNA repair. Presence of nuclear AhR protein is associated with ATM activation and chromatin relaxation indicated by acetylation of histone H3. Taken together, we could show, that beyond the function as a transcription factor the nuclear AhR is involved in the regulation of DNA repair. Reduction of nuclear AhR inhibits DNA-double stand repair and radiosensitizes cells. First hints for its molecular mechanism suggest a role during ATM activation and chromatin relaxation, both essential for DNA repair. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Development, sensibility, and reliability of the Toronto Axial Spondyloarthritis Questionnaire in inflammatory bowel disease.

PubMed

Alnaqbi, Khalid A; Touma, Zahi; Passalent, Laura; Johnson, Sindhu R; Tomlinson, George A; Carty, Adele; Inman, Robert D

2013-10-01

There is an unacceptable delay in the diagnosis of axial spondyloarthritis (axSpA) in its early stages among patients at high risk, in particular those with inflammatory bowel disease (IBD). Our objectives were to develop a sensible and reliable questionnaire to identify undetected axSpA among patients with IBD. Literature was reviewed for item generation in the Toronto axSpA Questionnaire on IBD (TASQ-IBD). Sensibility of the questionnaire was assessed among healthcare professionals and patients. This assessment was related to purpose and framework (clinical function, clinical justification, and clinical applicability), face validity, comprehensiveness [oligo-variability (limiting the questionnaire to important items) and transparency], replicability, content validity, and feasibility. The test-retest reliability study was administered to 77 patients with established IBD and axSpA. Kappa agreement coefficients and absolute agreement were calculated for items. Three domains included IBD, inflammatory back symptoms, and extraaxial features. The entry criterion required a patient to have IBD and back pain or stiffness that ever persisted for ≥ 3 months. Iterative sensibility assessment involved 16 items and a diagram of the back. Kappa coefficients ranged from 0.81-1.00 for each item. Absolute agreement across all items ranged from 91% to 100%. TASQ-IBD is a newly developed, sensible, and reliable case-finding questionnaire to be administered to patients with IBD who have ever had chronic back pain or stiffness persisting for ≥ 3 months. It should facilitate identification and timely referral of patients with IBD to rheumatologists and minimize the delay in diagnosis of axSpA. Consequently, it should assess the prevalence of axSpA in IBD.

Induction and quantification of gammma-H2AX foci following cx- and gamma-irradiaton

NASA Technical Reports Server (NTRS)

Leatherbarrow, E. L.; Cucinotta, F. A.; O'Neill, Peter

2004-01-01

Following DNA damage the histone H2AX becomes phosphorylated and can be visualised by immunofluorescence as an indicator of DSBs in individual cells. Using a wild type hamster cell line (V79-4) exposed to either a-particles or to Co-60 gamma-rays to induce DNA DSBs at different doses (20-200OmGy), the dose dependent induction of gamma-H2AX foci were scored both manually (by eye) and using image analysis. A linearly dependence on dose was found for both radiations. The number of DSBs determined by image analysis after a post-irradiation period of 30 minutes at 37 C, is 16.6 foci/cell/Gy for alpha-irradiation and 12.2 foci/cell/Gy for gamma-irradiation; the latter being 3-4 times the levels observed by eye and comparable to gamma-radiation-induced levels of prompt DSBs more recently reported using pulse field gel electrophoresis (approx. 16 DSBs/Gy). The average size of the gamma-H2AX foci induced by alpha-irradiation (0.30 square micrometers) is approximately 1.5 times larger than those induced by gamma-irradiation (0.19 square micrometers). The timescale of induction and removal of DSBs up to 24 hours post-irradiation, was investigated with gamma-H2AX foci levels found to remain significantly higher than controls for 4 or 6 hours in gamma-irradiated samples or alpha irradiated samples, respectively. These results demonstrate that not only gamma radiation but also alpha-radiation induce phosphorylation of the H2AX histone in response to DSBs even at low doses (20mGy for gamma-rays, 1 track/cell on average for alpha-particles) and the variation in size and dephosphorylation of the induced foci is dependent on radiation quality (LET).

γH2AX assay in ex vivo irradiated tumour specimens: A novel method to determine tumour radiation sensitivity in patient-derived material.

PubMed

Menegakis, Apostolos; von Neubeck, Cläre; Yaromina, Ala; Thames, Howard; Hering, Sandra; Hennenlotter, Joerg; Scharpf, Marcus; Noell, Susan; Krause, Mechthild; Zips, Daniel; Baumann, Michael

2015-09-01

To establish a clinically applicable protocol for quantification of residual γH2AX foci in ex vivo irradiated tumour samples and to apply this method in a proof-of-concept feasibility study to patient-derived tumour specimens. Evaluation of γH2AX foci formation and disappearance in excised FaDu tumour specimens after (a) different incubation times in culture medium, 4Gy irradiation and fixation after 24h (cell recovery), (b) 10h medium incubation, 4Gy irradiation and fixation after various time points (double strand break repair kinetics), and (c) 10h medium incubation, irradiation with graded single radiation doses and fixation after 24h (dose-response). The optimised protocol was applied to patient-derived samples of seminoma, prostate cancer and glioblastoma multiforme. Post excision or biopsy, tumour tissues showed stable radiation-induced γH2AX foci values in oxic cells after >6h of recovery in medium. Kinetics of foci disappearance indicated a plateau of residual foci after >12h following ex vivo irradiation. Fitting the dose-response of residual γH2AX foci yielded slopes comparable with in situ irradiation of FaDu tumours. Significant differences in the slopes of ex vivo irradiated patient-derived tumour samples were found. A novel clinically applicable method to quantify residual γH2AX foci in ex vivo irradiated tumour samples was established. The first clinical results suggest that this method allows to distinguish between radiosensitive and radioresistant tumour types. These findings support further translational evaluation of this assay to individualise radiation therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comparison of two methods for measuring γ-H2AX nuclear fluorescence as a marker of DNA damage in cultured human cells: applications for microbeam radiation therapy

NASA Astrophysics Data System (ADS)

Anderson, D.; Andrais, B.; Mirzayans, R.; Siegbahn, E. A.; Fallone, B. G.; Warkentin, B.

2013-06-01

Microbeam radiation therapy (MRT) delivers single fractions of very high doses of synchrotron x-rays using arrays of microbeams. In animal experiments, MRT has achieved higher tumour control and less normal tissue toxicity compared to single-fraction broad beam irradiations of much lower dose. The mechanism behind the normal tissue sparing of MRT has yet to be fully explained. An accurate method for evaluating DNA damage, such as the γ-H2AX immunofluorescence assay, will be important for understanding the role of cellular communication in the radiobiological response of normal and cancerous cell types to MRT. We compare two methods of quantifying γ-H2AX nuclear fluorescence for uniformly irradiated cell cultures: manual counting of γ-H2AX foci by eye, and an automated, MATLAB-based fluorescence intensity measurement. We also demonstrate the automated analysis of cell cultures irradiated with an array of microbeams. In addition to offering a relatively high dynamic range of γ-H2AX signal versus irradiation dose ( > 10 Gy), our automated method provides speed, robustness, and objectivity when examining a series of images. Our in-house analysis facilitates the automated extraction of the spatial distribution of the γ-H2AX intensity with respect to the microbeam array — for example, the intensities in the peak (high dose area) and valley (area between two microbeams) regions. The automated analysis is particularly beneficial when processing a large number of samples, as is needed to systematically study the relationship between the numerous dosimetric and geometric parameters involved with MRT (e.g., microbeam width, microbeam spacing, microbeam array dimensions, peak dose, valley dose, and geometric arrangement of multiple arrays) and the resulting DNA damage.

Ab initio study of irradiation tolerance for different M{sub n+1}AX{sub n} phases: Ti{sub 3}SiC{sub 2} and Ti{sub 3}AlC{sub 2}

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

Zhao, Shijun; Xue, Jianming, E-mail: jmxue@pku.edu.cn; Wang, Yugang

2014-01-14

Layered ternary M{sub n+1}AX{sub n} (MAX) materials are recently proposed to be promising candidates for future fission and fusion programmes because of their unique properties inherited from both ceramics and metals. However, different M{sub n+1}AX{sub n} materials demonstrate different behaviors when exposed to energetic neutron or ion irradiations. Based on first-principles calculations, we have investigated the irradiation tolerance of two typical M{sub n+1}AX{sub n} materials: Ti{sub 3}SiC{sub 2} and Ti{sub 3}AlC{sub 2} from two aspects. First, we make a detailed analysis on the interatomic bonding characters, which are believed to be responsible for the resistance to radiation-induced amorphization. Second, themore » formation energies of various intrinsic and antisite defects in these two compounds are calculated in order to elucidate their amorphization mechanism. Our results show that the absence of orbitals overlap of Al-C in Ti{sub 3}AlC{sub 2} renders it more resistant to amorphization compared to Ti{sub 3}SiC{sub 2}. In addition, the antisite defects Al{sub Ti(1)} and Al{sub Ti(2)} in Ti{sub 3}AlC{sub 2} have much lower formation energies compared to Si{sub Ti(1)} and Si{sub Ti(2)} in Ti{sub 3}SiC{sub 2}, which implies that the replacement of Ti with Al is easier than Si, thus providing an alternative way to accommodate the defects resulted from irradiation damage cascades. These results indicate that Ti{sub 3}AlC{sub 2} is more irradiation tolerant than Ti{sub 3}SiC{sub 2}, in accordance with experimental observations. Our results have profound implications for the choice of appropriate MAX phase with best performance to be used in next reaction reactors.« less

Assessing the accuracy of using oscillating gradient spin echo sequences with AxCaliber to infer micron-sized axon diameters.

PubMed

Mercredi, Morgan; Vincent, Trevor J; Bidinosti, Christopher P; Martin, Melanie

2017-02-01

Current magnetic resonance imaging (MRI) axon diameter measurements rely on the pulsed gradient spin-echo sequence, which is unable to provide diffusion times short enough to measure small axon diameters. This study combines the AxCaliber axon diameter fitting method with data generated from Monte Carlo simulations of oscillating gradient spin-echo sequences (OGSE) to infer micron-sized axon diameters, in order to determine the feasibility of using MRI to infer smaller axon diameters in brain tissue. Monte Carlo computer simulation data were synthesized from tissue geometries of cylinders of different diameters using a range of gradient frequencies in the cosine OGSE sequence . Data were fitted to the AxCaliber method modified to allow the new pulse sequence. Intra- and extra-axonal water were studied separately and together. The simulations revealed the extra-axonal model to be problematic. Rather than change the model, we found that restricting the range of gradient frequencies such that the measured apparent diffusion coefficient was constant over that range resulted in more accurate fitted diameters. Thus a careful selection of frequency ranges is needed for the AxCaliber method to correctly model extra-axonal water, or adaptations to the method are needed. This restriction helped reduce the necessary gradient strengths for measurements that could be performed with parameters feasible for a Bruker BG6 gradient set. For these experiments, the simulations inferred diameters as small as 0.5 μm on square-packed and randomly packed cylinders. The accuracy of the inferred diameters was found to be dependent on the signal-to-noise ratio (SNR), with smaller diameters more affected by noise, although all diameter distributions were distinguishable from one another for all SNRs tested. The results of this study indicate the feasibility of using MRI with OGSE on preclinical scanners to infer small axon diameters.

X-ray induced formation of γ-H2AX foci after full-field digital mammography and digital breast-tomosynthesis.

PubMed

Schwab, Siegfried A; Brand, Michael; Schlude, Ina-Kristin; Wuest, Wolfgang; Meier-Meitinger, Martina; Distel, Luitpold; Schulz-Wendtland, Ruediger; Uder, Michael; Kuefner, Michael A

2013-01-01

To determine in-vivo formation of x-ray induced γ-H2AX foci in systemic blood lymphocytes of patients undergoing full-field digital mammography (FFDM) and to estimate foci after FFDM and digital breast-tomosynthesis (DBT) using a biological phantom model. The study complies with the Declaration of Helsinki and was performed following approval by the ethic committee of the University of Erlangen-Nuremberg. Written informed consent was obtained from every patient. For in-vivo tests, systemic blood lymphocytes were obtained from 20 patients before and after FFDM. In order to compare in-vivo post-exposure with pre-exposure foci levels, the Wilcoxon matched pairs test was used. For in-vitro experiments, isolated blood lymphocytes from healthy volunteers were irradiated at skin and glandular level of a porcine breast using FFDM and DBT. Cells were stained against the phosphorylated histone variant γ-H2AX, and foci representing distinct DNA damages were quantified. Median in-vivo foci level/cell was 0.086 (range 0.067-0.116) before and 0.094 (0.076-0.126) after FFDM (p = 0.0004). In the in-vitro model, the median x-ray induced foci level/cell after FFDM was 0.120 (range 0.086-0.140) at skin level and 0.035 (range 0.030-0.050) at glandular level. After DBT, the median x-ray induced foci level/cell was 0.061 (range 0.040-0.081) at skin level and 0.015 (range 0.006-0.020) at glandular level. In patients, mammography induces a slight but significant increase of γ-H2AX foci in systemic blood lymphocytes. The introduced biological phantom model is suitable for the estimation of x-ray induced DNA damages in breast tissue in different breast imaging techniques.

Effects of interstellar dust scattering on the X-ray eclipses of the LMXB AX J1745.6-2901 in the Galactic Centre

NASA Astrophysics Data System (ADS)

Jin, Chichuan; Ponti, Gabriele; Haberl, Frank; Smith, Randall; Valencic, Lynne

2018-07-01

AX J1745.6-2901 is an eclipsing low-mass X-ray binary in the Galactic Centre (GC). It shows significant X-ray excess emission during the eclipse phase, and its eclipse light curve shows an asymmetric shape. We use archival XMM-Newton and Chandra observations to study the origin of these peculiar X-ray eclipsing phenomena. We find that the shape of the observed X-ray eclipse light curves depends on both photon energy and the shape of the source extraction region, and also shows differences between the two instruments. By performing detailed simulations for the time-dependent X-ray dust-scattering halo, as well as directly modelling the observed eclipse and non-eclipse halo profiles of AX J1745.6-2901, we obtained solid evidence that its peculiar eclipse phenomena are indeed caused by the X-ray dust scattering in multiple foreground dust layers along the line of sight (LOS). The apparent dependence on the instruments is caused by different instrumental point spread functions. Our results can be used to assess the influence of dust-scattering in other eclipsing X-ray sources, and raise the importance of considering the timing effects of dust-scattering halo when studying the variability of other X-ray sources in the GC, such as Sgr A⋆. Moreover, our study of halo eclipse reinforces the existence of a dust layer local to AX J1745.6-2901 as reported by Jin et al. (2017), as well as identifying another dust layer within a few hundred parsecs to the Earth, containing up to several tens of percent LOS dust, which is likely to be associated with the molecular clouds in the Solar neighbourhood. The remaining LOS dust is likely to be associated with the molecular clouds located in the Galactic disc in-between.

A cross-sectional study on factors associated with patient-physician discordance in global assessment of patients with axial spondyloarthritis: an Asian perspective.

PubMed

Wang, Charmaine Tze May; Fong, Warren; Kwan, Yu Heng; Phang, Jie Kie; Lui, Nai Lee; Leung, Ying Ying; Thumboo, Julian; Cheung, Peter P

2018-06-19

To identify the factors associated with patient-physician discordance in patients with axial spondyloarthritis (axSpA) in an Asian population. A cross-sectional study was conducted in two tertiary referral centers in Singapore. Patients with axSpA who fulfilled Assessment in Ankylosing Spondylitis International Working Group 2009 criteria for axSpA were included in the study. Socio-demographics, clinical, laboratory and patient-reported outcomes data were collected during study visits from 2014 to 2015. We performed univariate and multivariate linear regression analyses to evaluate the factors associated with patient-physician discordance, which we defined as the difference between Patient Global Assessment and Physician Global Assessment. Included in the study were 298 axSpA patients: 82% male, 81% Chinese, median age 40 (20-78) years, median disease duration 9 (0.1-48) years. 80% were on non-steroidal anti-inflammatory drugs and 23% on biologics. In univariate analysis, current age (β: 0.18, ρ = 0.06), duration of disease (β: 0.34, ρ = 0.03), post-secondary education level (β: -10.82, ρ = 0.03), global pain score (β: 0.33, ρ < 0.01), Bath Ankylosing Spondylitis Functional Index (β: 2.80, ρ < 0.01), Ankylosing Spondylitis Disease Activity Score C-reactive protein (β: 4.63, ρ < 0.01) and current use of biologics (β: 10.97, ρ < 0.01) were associated with patient-physician discordance. In multivariate analysis, global pain score (β: 0.32, ρ < 0.01), post-secondary education level (β: -12.80, ρ = 0.01) and current biologics use (β: 16.21, ρ < 0.01) were associated with patient-physician discordance. Higher global pain score, lower educational level and current biologics use were associated with greater patient-physician discordance. These factors should be considered during shared decision making. © 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Effects of HMW-GS Ax1 or Dx2 absence on the glutenin polymerization and gluten micro structure of wheat (Triticum aestivum L.).

PubMed

Gao, Xin; Liu, Tianhong; Ding, Mengyun; Wang, Jun; Li, Chunlian; Wang, Zhonghua; Li, Xuejun

2018-02-01

Wheat (Triticum aestivum L.) dough strength and extensibility are mainly determined by the polymerization of glutenin. The number of high-molecular-weight glutenin subunits (HMW-GS) differs in various wheat varieties due to the silencing of some genes. The effects of Ax1 or Dx2 subunit absence on glutenin polymerization, dough mixing properties and gluten micro structure were investigated with two groups of near-isogenic lines. The results showed that Ax1 or Dx2 absence decreased the accumulation rate of glutenin polymers and thus delayed the rapid increase period for glutenin polymerization by at least ten days, which led to lower percentage of polymeric protein in mature grain. Ax1 or Dx2 absence significantly decreased the dough development time and dough stability, but increased the uniformity of micro structure. Lacunarity, derived from quantitative analysis of gluten network, is suggested as a new indicator for wheat quality. Copyright © 2017 Elsevier Ltd. All rights reserved.

Probing the interstellar dust towards the Galactic Centre: dust-scattering halo around AX J1745.6-2901

NASA Astrophysics Data System (ADS)

Jin, Chichuan; Ponti, Gabriele; Haberl, Frank; Smith, Randall

2017-07-01

AX J1745.6-2901 is an X-ray binary located at only 1.45 arcmin from Sgr A⋆, showcasing a strong X-ray dust-scattering halo. We combine Chandra and XMM-Newton observations to study the halo around this X-ray binary. Our study shows two major thick dust layers along the line of sight (LOS) towards AX J1745.6-2901. The LOS position and NH of these two layers depend on the dust grain models with different grain size distributions and abundances. But for all the 19 dust grain models considered, dust layer-1 is consistently found to be within a fractional distance of 0.11 (mean value: 0.05) to AX J1745.6-2901 and contains only (19-34) per cent (mean value: 26 per cent) of the total LOS dust. The remaining dust is contained in layer-2, which is distributed from the Earth up to a mean fractional distance of 0.64. A significant separation between the two layers is found for all the dust grain models, with a mean fractional distance of 0.31. Besides, an extended wing component is discovered in the halo, which implies a higher fraction of dust grains with typical sizes ≲590 Å than considered in current dust grain models. Assuming AX J1745.6-2901 is 8 kpc away, dust layer-2 would be located in the Galactic disc several kpc away from the Galactic Centre (GC). The dust scattering halo biases the observed spectrum of AX J1745.6-2901 severely in both spectral shape and flux, and also introduces a strong dependence on the size of the instrumental point spread function and the source extraction region. We build xspec models to account for this spectral bias, which allow us to recover the intrinsic spectrum of AX J1745.6-2901 free from dust-scattering opacity. If dust layer-2 also intervenes along the LOS to Sgr A⋆ and other nearby GC sources, a significant spectral correction for the dust-scattering opacity would be necessary for all these GC sources.

Perception of Non-Native Consonant Length Contrast: The Role of Attention in Phonetic Processing

ERIC Educational Resources Information Center

Porretta, Vincent J.; Tucker, Benjamin V.

2015-01-01

The present investigation examines English speakers' ability to identify and discriminate non-native consonant length contrast. Three groups (L1 English No-Instruction, L1 English Instruction, and L1 Finnish control) performed a speeded forced-choice identification task and a speeded AX discrimination task on Finnish non-words (e.g.…

Grinding the Antitesting Ax: More Bias than Evidence behind NRC Panel's Conclusions

ERIC Educational Resources Information Center

Hanushek, Eric A.

2012-01-01

In all the acrimonious discussion surrounding No Child Left Behind Act of 2001 (NCLB), surprisingly little attention has been given to the actual impact of that legislation and other accountability systems on student performance. Now a reputable body, a committee set up by the National Research Council (NRC), the research arm of the National…

Nonstarch polysaccharides in wheat flour wire-cut cookie making.

PubMed

Guttieri, Mary J; Souza, Edward J; Sneller, Clay

2008-11-26

Nonstarch polysaccharides in wheat flour have significant capacity to affect the processing quality of wheat flour dough and the finished quality of wheat flour products. Most research has focused on the effects of arabinoxylans (AX) in bread making. This study found that water-extractable AX and arabinogalactan peptides can predict variation in pastry wheat quality as captured by the wire-cut cookie model system. The sum of water-extractable AX plus arabinogalactan was highly predictive of cookie spread factor. The combination of cookie spread factor and the ratio of water-extractable arabinose to xylose predicted peak force of the three-point bend test of cookie texture.

Nonlinear Equatorial Spread F: Spatially Large Bubbles Resulting from Large Horizontal Scale Initial Perturbations.

DTIC Science & Technology

1980-02-06

Hk~ NAT;ONAL BUR[AUJ (1 STANDARDS 1%3-, $LEVE1 NR L Memomduum Report 4154 ILII Nonlinear Equatorial Spread F: Spatially Large Bubbles Resulting from...Washington, DC 20375 and 67-0883-0-0 _DNA qubtask S99OAXHC 41 II. CONTROLLING OFFICE NAME AND ADDRESS 12 . REPORT DATE Defense Nuclear Agency, Washington...Perturbation A: n(yO) i-e 23 [CIDS ] 8 Ax <Jxj< 16Ax n(x,y,0) 1 1 x1 > 16 Ax n (y,O) ( 12 ) Perturbation B: n(%,y,0) 1 -e 3 cos ( (13) n 0 (y,) \\2xm 7

The effects of galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex on Eimeria acervulina infection in broiler chicks

USDA-ARS?s Scientific Manuscript database

Fermentable carbohydrates may enhance the ability of the gastrointestinal tract to defend against pathogenic infection. We hypothesized that a mannose-rich, galactoglucomannan oligosaccharide-arabinoxylan (GGMO-AX) complex would positively impact immune status and prevent weight loss resulting from...

Impaired fear inhibition learning predicts the persistence of symptoms of posttraumatic stress disorder (PTSD).

PubMed

Sijbrandij, Marit; Engelhard, Iris M; Lommen, Miriam J J; Leer, Arne; Baas, Johanna M P

2013-12-01

Recent cross-sectional studies have shown that the inability to suppress fear under safe conditions is a key problem in people with posttraumatic stress disorder (PTSD). The current longitudinal study examined whether individual differences in fear inhibition predict the persistence of PTSD symptoms. Approximately 2 months after deployment to Afghanistan, 144 trauma-exposed Dutch soldiers were administered a conditional discrimination task (AX+/BX-). In this paradigm, A, B, and X are neutral stimuli. X combined with A is paired with a shock (AX+ trials); X combined with B is not (BX- trials). Fear inhibition was measured (AB trials). Startle electromyogram responses and shock expectancy ratings were recorded. PTSD symptoms were measured at 2 months and at 9 months after deployment. Results showed that greater startle responses during AB trials in individuals who discriminated between danger (AX+) and safety (BX-) during conditioning, predicted higher PTSD symptoms at 2 months and 9 months post-deployment. The predictive effect at 9 months remained significant after controlling for critical incidents during previous deployments and PTSD symptoms at 2 months. Responses to AX+ or BX- trials, or discrimination learning (AX+ minus BX-) did not predict PTSD symptoms. It is concluded that impaired fear inhibition learning seems to be involved in the persistence of PTSD symptoms. Copyright © 2013 Elsevier Ltd. All rights reserved.

DNA damage signaling regulates age-dependent proliferative capacity of quiescent inner ear supporting cells

PubMed Central

Laos, Maarja; Anttonen, Tommi; Kirjavainen, Anna; Hällström, Taija af; Laiho, Marikki; Pirvola, Ulla

2014-01-01

Supporting cells (SCs) of the cochlear (auditory) and vestibular (balance) organs hold promise as a platform for therapeutic regeneration of the sensory hair cells. Prior data have shown proliferative restrictions of adult SCs forced to re-enter the cell cycle. By comparing juvenile and adult SCs in explant cultures, we have here studied how proliferative restrictions are linked with DNA damage signaling. Cyclin D1 overexpression, used to stimulate cell cycle re-entry, triggered higher proliferative activity of juvenile SCs. Phosphorylated form of histone H2AX (γH2AX) and p53 binding protein 1 (53BP1) were induced in a foci-like pattern in SCs of both ages as an indication of DNA double-strand break formation and activated DNA damage response. Compared to juvenile SCs, γH2AX and the repair protein Rad51 were resolved with slower kinetics in adult SCs, accompanied by increased apoptosis. Consistent with the in vitro data, in a Rb mutant mouse model in vivo, cell cycle re-entry of SCs was associated with γH2AX foci induction. In contrast to cell cycle reactivation, pharmacological stimulation of SC-to-hair-cell transdifferentiation in vitro did not trigger γH2AX. Thus, DNA damage and its prolonged resolution are critical barriers in the efforts to stimulate proliferation of the adult inner ear SCs. PMID:25063730

Predictive Biomarkers of Radiation Sensitivity in Rectal Cancer

NASA Astrophysics Data System (ADS)

Tut, Thein Ga

Colorectal cancer (CRC) is the third most common cancer in the world. Australia, New Zealand, Canada, the United States, and parts of Europe have the highest incidence rates of CRC. China, India, South America and parts of Africa have the lowest risk of CRC. CRC is the second most common cancer in both sexes in Australia. Even though the death rates from CRC involving the colon have diminished, those arising from the rectum have revealed no improvement. The greatest obstacle in attaining a complete surgical resection of large rectal cancers is the close anatomical relation to surrounding structures, as opposed to the free serosal surfaces enfolding the colon. To assist complete resection, pre-operative radiotherapy (DXT) can be applied, but the efficacy of ionising radiation (IR) is extremely variable between individual tumours. Reliable predictive marker/s that enable patient stratification in the application of this otherwise toxic therapy is still not available. Current therapeutic management of rectal cancer can be improved with the availability of better predictive and prognostic biomarkers. Proteins such as Plk1, gammaH2AX and MMR proteins (MSH2, MSH6, MLH1 and PMS2), involved in DNA damage response (DDR) pathway may be possible biomarkers for radiation response prediction and prognostication of rectal cancer. Serine/threonine protein kinase Plk1 is overexpressed in most of cancers including CRC. Plk1 functional activity is essential in the restoration of DNA damage following IR, which causes DNA double strand break (DSB). The earliest manifestation of this reparative process is histone H2AX phosphorylation at serine 139, leading to gammaH2AX. Colorectal normal mucosa showed the lowest level of gammaH2AX with gradually increasing levels in early adenoma and then in advanced malignant colorectal tissues, leading to the possibility that gammaH2AX may be a prospective biomarker in rectal cancer management. There are numerous publications regarding DNA mismatch repair (MMR) proteins, the insufficiency of which is characteristic of CRCs with microsatellite instability (MSI). MSI may enable unlimited replicative potential of malignant cell that leads to radiation injury resistance. Therefore, these proteins were characterized in both CRC cell lines (MMR proteins) and different (core and invasive front) rectal cancer tissues (Plk1, gammaH2AX and MMR proteins) exposed to radiation. Histopathological grading of tumour regression was performed following radiotherapy in rectal cancer as a marker of radiotherapy response and a surrogate indicator of patient prognosis. Though MMR protein expressions correlated with improved in vitro cell survival following radiation, these findings could only be partially replicated in patient tissue samples. This may not be entirely unexpected, given intratumoural heterogeneity in genetic profiles and oxygenation between individual cancer cells, their interaction with stromal environment and a multitude of other factors that cannot be adequately replicated in cell line experiments. In our rectal cancer patient cohort, histopathological regression following radiotherapy did appear to correlate with better clinical outcome, but certainly no replacement for the routine pTNM staging with which it was compared. Overexpression of Plk1 in the primary rectal cancer also correlates with poor tumour regression and reduced overall survival. High level of gammaH2AX correlates with higher tumour stage, perineural invasion and vascular invasion. However, interpretation of the results is limited by the small number of positivity amongst the cohort, with respect to gammaH2AX and MMR proteins. The combined analysis of all the proteins examined in this thesis revealed no interactions, possibly suggesting these biomarkers act individually within the DDR pathway, rather than in a demonstrably interdependent manner. Though our results are mixed, finding biomarkers predictive of radiation response is nonetheless critical. Enhancing the radiosensitivity of cancers through manipulating the functional activity and/or expression of prospective biomarkers could conceivably enhance tumour response to the level that the extent of consequent surgical resection can be minimized.

Variability in Arabinoxylan, Xylanase activity and Xylanase inhibitor levels in hard spring wheat

USDA-ARS?s Scientific Manuscript database

Arabinoxylans (AX), xylanase, and xylanase inhibitors have an important role in many cereal food processing applications. The effect of genotype (G), growing location (L), and their interaction (G*L) on AX, apparent xylanase and apparent xylanase inhibition activities of Triticum aestivum xylanase i...

2-Oxoamide inhibitors of cytosolic group IVA phospholipase A2 with reduced lipophilicity.

PubMed

Antonopoulou, Georgia; Magrioti, Victoria; Kokotou, Maroula G; Nikolaou, Aikaterini; Barbayianni, Efrosini; Mouchlis, Varnavas D; Dennis, Edward A; Kokotos, George

2016-10-01

Cytosolic GIVA phospholipase A2 (GIVA cPLA2) initiates the eicosanoid pathway of inflammation and thus inhibitors of this enzyme constitute novel potential agents for the treatment of inflammatory diseases. Traditionally, GIVA cPLA2 inhibitors have suffered systemically from high lipophilicity. We have developed a variety of long chain 2-oxoamides as inhibitors of GIVA PLA2. Among them, AX048 was found to produce a potent analgesic effect. We have now reduced the lipophilicity of AX048 by replacing the long aliphatic chain with a chain containing an ether linked aromatic ring with in vitro inhibitory activities similar to AX048. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hit-to-lead optimization and kinase selectivity of imidazo[1,2-a]quinoxalin-4-amine derived JNK1 inhibitors.

PubMed

Li, Bei; Cociorva, Oana M; Nomanbhoy, Tyzoon; Weissig, Helge; Li, Qiang; Nakamura, Kai; Liyanage, Marek; Zhang, Melissa C; Shih, Ann Y; Aban, Arwin; Hu, Yi; Cajica, Julia; Pham, Lan; Kozarich, John W; Shreder, Kevin R

2013-09-15

As the result of a rhJNK1 HTS, the imidazo[1,2-a]quinoxaline 1 was identified as a 1.6 μM rhJNK1 inhibitor. Optimization of this compound lead to AX13587 (rhJNK1 IC50=160 nM) which was co-crystallized with JNK1 to identify key molecular interactions. Kinase profiling against 125+ kinases revealed AX13587 was an inhibitor of JNK, MAST3, and MAST4 whereas its methylene homolog AX14373 (native JNK1 IC50=47 nM) was a highly specific JNK inhibitor. Copyright © 2013 Elsevier Ltd. All rights reserved.

The c-ring stoichiometry of ATP synthase is adapted to cell physiological requirements of alkaliphilic Bacillus pseudofirmus OF4

PubMed Central

Preiss, Laura; Klyszejko, Adriana L.; Hicks, David B.; Liu, Jun; Fackelmayer, Oliver J.; Yildiz, Özkan; Krulwich, Terry A.; Meier, Thomas

2013-01-01

The c-rings of ATP synthases consist of individual c-subunits, all of which harbor a conserved motif of repetitive glycine residues (GxGxGxG) important for tight transmembrane α-helix packing. The c-ring stoichiometry determines the number of ions transferred during enzyme operation and has a direct impact on the ion-to-ATP ratio, a cornerstone parameter of cell bioenergetics. In the extreme alkaliphile Bacillus pseudofirmus OF4, the glycine motif is replaced by AxAxAxA. We performed a structural study on two mutants with alanine-to-glycine changes using atomic force microscopy and X-ray crystallography, and found that mutants form smaller c12 rings compared with the WT c13. The molar growth yields of B. pseudofirmus OF4 cells on malate further revealed that the c12 mutants have a considerably reduced capacity to grow on limiting malate at high pH. Our results demonstrate that the mutant ATP synthases with either c12 or c13 can support ATP synthesis, and also underscore the critical importance of an alanine motif with c13 ring stoichiometry for optimal growth at pH >10. The data indicate a direct connection between the precisely adapted ATP synthase c-ring stoichiometry and its ion-to-ATP ratio on cell physiology, and also demonstrate the bioenergetic challenges and evolutionary adaptation strategies of extremophiles. PMID:23613590

Modifying a numerical algorithm for solving the matrix equation X + AX T B = C

NASA Astrophysics Data System (ADS)

Vorontsov, Yu. O.

2013-06-01

Certain modifications are proposed for a numerical algorithm solving the matrix equation X + AX T B = C. By keeping the intermediate results in storage and repeatedly using them, it is possible to reduce the total complexity of the algorithm from O( n 4) to O( n 3) arithmetic operations.

Three Interpretations of the Matrix Equation Ax = b

ERIC Educational Resources Information Center

Larson, Christine; Zandieh, Michelle

2013-01-01

Many of the central ideas in an introductory undergraduate linear algebra course are closely tied to a set of interpretations of the matrix equation Ax = b (A is a matrix, x and b are vectors): linear combination interpretations, systems interpretations, and transformation interpretations. We consider graphic and symbolic representations for each,…

Disappearance of the telomere dysfunction-induced stress response in fully senescent cells.

PubMed

Bakkenist, Christopher J; Drissi, Rachid; Wu, Jing; Kastan, Michael B; Dome, Jeffrey S

2004-06-01

Replicative senescence is a natural barrier to cellular proliferation that is triggered by telomere erosion and dysfunction. Here, we demonstrate that ATM activation and H2AX-gamma nuclear focus formation are sensitive markers of telomere dysfunction in primary human fibroblasts. Whereas the activated form of ATM and H2AX-gamma foci were rarely observed in early-passage cells, they were readily detected in late-passage cells. The ectopic expression of telomerase in late-passage cells abrogated ATM activation and H2AX-gamma focus formation, suggesting that these stress responses were the consequence of telomere dysfunction. ATM activation was induced in quiescent fibroblasts by inhibition of TRF2 binding to telomeres, indicating that telomere uncapping is sufficient to initiate the telomere signaling response; breakage of chromosomes with telomeric associations is not required for this activation. Although ATM activation and H2AX-gamma foci were readily observed in late-passage cells, they disappeared once cells became fully senescent, indicating that constitutive signaling from dysfunctional telomeres is not required for the maintenance of senescence.

Systematic identification of fragile sites via genome-wide location analysis of γ-H2AX

PubMed Central

Szilard, Rachel K.; Jacques, Pierre-Étienne; Laramée, Louise; Cheng, Benjamin; Galicia, Sarah; Bataille, Alain R.; Yeung, ManTek; Mendez, Megan; Bergeron, Maxime; Robert, François; Durocher, Daniel

2011-01-01

Phosphorylation of histone H2AX is an early response to DNA damage in eukaryotes. In Saccharomyces cerevisiae, DNA damage or replication fork stalling results in histone H2A phosphorylation to yield γ-H2A (yeast γ-H2AX) in a Mec1 (ATR)- and Tel1 (ATM)- dependent manner. Here, we describe the genome-wide location analysis of γ-H2A as a strategy to identify loci prone to engage the Mec1 and Tel1 pathways. Remarkably, γ-H2A enrichment overlaps with loci prone to replication fork stalling and is caused by the action of Mec1 and Tel1, indicating that these loci are prone to breakage. Moreover, about half the sites enriched for γ-H2A map to repressed protein-coding genes, and histone deacetylases are necessary for formation of γ-H2A at these loci. Finally, our work indicates that high resolution mapping of γ-H2AX is a fruitful route to map fragile sites in eukaryotic genomes. PMID:20139982

The effect of astaxanthin on the aging rat brain: gender-related differences in modulating inflammation.

PubMed

Balietti, Marta; Giannubilo, Stefano R; Giorgetti, Belinda; Solazzi, Moreno; Turi, Angelo; Casoli, Tiziana; Ciavattini, Andrea; Fattorettia, Patrizia

2016-01-30

Astaxanthin (Ax) is a ketocarotenoid of the xanthophyll family with activities such as antioxidation, preservation of the integrity of cell membranes and protection of the redox state and functional integrity of mitochondria. The aim of this study was to investigate potential gender-related differences in the effect of Ax on the aging rat brain. In females, interleukin 1 beta (IL1β) was significantly lower in treated rats in both cerebral areas, and in the cerebellum, treated animals also had significantly higher IL10. In males, no differences were found in the cerebellum, but in the hippocampus, IL1β and IL10 were significantly higher in treated rats. These are the first results to show gender-related differences in the effect of Ax on the aging brain, emphasizing the necessity to carefully analyze female and male peculiarities when the anti-aging potentialities of this ketocarotenoid are evaluated. The observations lead to the hypothesis that Ax exerts different anti-inflammatory effects in female and male brains. © 2015 Society of Chemical Industry.

X-Ray Induced DNA Damage and Repair in Germ Cells of PARP1−/− Male Mice

PubMed Central

Villani, Paola; Fresegna, Anna Maria; Ranaldi, Roberto; Eleuteri, Patrizia; Paris, Lorena; Pacchierotti, Francesca; Cordelli, Eugenia

2013-01-01

Poly(ADP-ribose)polymerase-1 (PARP1) is a nuclear protein implicated in DNA repair, recombination, replication, and chromatin remodeling. The aim of this study was to evaluate possible differences between PARP1−/− and wild-type mice regarding induction and repair of DNA lesions in irradiated male germ cells. Comet assay was applied to detect DNA damage in testicular cells immediately, and two hours after 4 Gy X-ray irradiation. A similar level of spontaneous and radiation-induced DNA damage was observed in PARP1−/− and wild-type mice. Conversely, two hours after irradiation, a significant level of residual damage was observed in PARP1−/− cells only. This finding was particularly evident in round spermatids. To evaluate if PARP1 had also a role in the dynamics of H2AX phosphorylation in round spermatids, in which γ-H2AX foci had been shown to persist after completion of DNA repair, we carried out a parallel analysis of γ-H2AX foci at 0.5, 2, and 48 h after irradiation in wild-type and PARP1−/− mice. No evidence was obtained of an effect of PARP1 depletion on H2AX phosphorylation induction and removal. Our results suggest that, in round spermatids, under the tested experimental conditions, PARP1 has a role in radiation-induced DNA damage repair rather than in long-term chromatin modifications signaled by phosphorylated H2AX. PMID:24009020

Dose response and repair kinetics of gamma-H2AX foci induced by in vitro irradiation of whole blood and T-lymphocytes with X- and gamma-radiation.

PubMed

Beels, Laurence; Werbrouck, Joke; Thierens, Hubert

2010-09-01

Dose response and repair kinetics of phosphorylated histone H2A isoform X (gamma-H2AX) foci in T-lymphocytes were investigated in the low-dose range after in vitro irradiation of whole blood and T-lymphocytes with 100 kVp X-rays and (60)Co gamma-rays. Whole blood or isolated T-lymphocytes were irradiated in vitro and gamma-H2AX foci were scored. Dose response was determined in the 0-500 mGy dose range. Foci kinetics were studied at doses of 5 and 200 mGy up to 24 h post-irradiation. After X-irradiation, the dose response for whole blood shows a biphasic behaviour with a low-dose hypersensitivity, which is less pronounced for isolated T-lymphocytes. In contrast, gamma-radiation shows a linear dose response for both irradiation conditions. Concerning repair kinetics, delayed repair was found after X-ray whole blood irradiation (5 and 200 mGy) with 40% of the foci persisting 24 h post-irradiation. This number of foci is reduced to 10% after irradiation of isolated T-lymphocytes with 200 mGy X-rays. On the contrary, gamma-H2AX foci are reduced to background levels 24 h post-irradiation with 200 mGy (60)Co gamma-rays. gamma-H2AX foci response and repair kinetics depend on irradiation conditions and radiation quality, possibly linked to Bystander response.

Determinants of psychological well-being in axial spondyloarthritis: an analysis based on linked claims and patient-reported survey data.

PubMed

Redeker, Imke; Hoffmann, Falk; Callhoff, Johanna; Haibel, Hildrun; Sieper, Joachim; Zink, Angela; Poddubnyy, Denis

2018-07-01

The aim of this study was to assess the psychological well-being and to analyse factors associated with depressive symptoms in axial spondyloarthritis (axSpA). A stratified random sample of subjects with a diagnosis of axSpA (International Classification of Diseases, Tenth Revision, German Modification M45) was drawn from health insurance data in Germany. These persons received a postal questionnaire on disease-related, psychological and lifestyle factors as well as socioeconomic status. Additional information to verify the axSpA diagnosis was also collected. The psychological well-being was assessed by means of the 5-item WHO Well-Being Index (WHO-5), which is considered a screening tool for depression. The following established cut-offs on the WHO-5 were applied: >50: good well-being, no depressive symptoms; 29-50: mild depressive symptoms; ≤28: moderate-to-severe depressive symptoms. Information on comorbidities, drug prescriptions and non-pharmacological treatment was retrieved from claims data and linked to the questionnaire data. A total of 1736 persons with a confirmed axSpA diagnosis were included. Using the cut-offs on the WHO-5, 533 persons (31%) were found to have moderate-to-severe depressive symptoms, 479 (28%) had mild depressive symptoms and 724 (42%) had a good well-being. Multivariable logistic regression revealed that higher disease activity, higher level of functional impairment, lower income, self-reported stress and lack of exercise, and younger age represent factors associated with moderate-to-severe depressive symptoms. The prevalence of depressive symptoms in axSpA subjects is high and associated with disease-related parameters, socioeconomic status and lifestyle factors. These findings highlight the need for the careful evaluation of depressive symptoms as a part of the management strategy for axSpA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Improvements in workplace and household productivity with certolizumab pegol treatment in axial spondyloarthritis: results to week 96 of a phase III study

PubMed Central

Braun, Jürgen; Rudwaleit, Martin; Purcaru, Oana; Kavanaugh, Arthur F

2018-01-01

Objectives To evaluate the effect of certolizumab pegol (CZP) on work and household productivity, and on participation in family, social and leisure activities in patients with axial spondyloarthritis (axSpA), including ankylosing spondylitis (AS) and non-radiographic (nr-) axSpA. Methods RAPID-axSpA (NCT01087762) was a phase III, double-blind, placebo-controlled trial to week (Wk) 24, dose-blind to Wk48 and open-label to Wk204. A total of 325 patients were randomised 1:1:1 to placebo, CZP 200 mg Q2W or CZP 400 mg Q4W. The validated arthritis-specific Work Productivity Survey assessed the impact of axSpA on work and household productivity and participation in social activities during the preceding month. Data are shown to Wk96, with responses compared between treatment arms (placebo vs CZP 200 mg and 400 mg dose groups combined) and subpopulations using a non-parametric bootstrap-t method. Results At baseline, 63.2% of placebo and 72.0% of CZP patients were employed. By Wk24, CZP patients reported on average 1.0 fewer days of absenteeism and 2.6 fewer days of presenteeism per month, compared with 0.4 and 0.9 fewer days for placebo. At home, by Wk24, CZP patients reported on average 3.0 household work days gained per month versus 1.3 for placebo. CZP patients reported fewer days with reduced household productivity or days lost for social participation. Similar improvements were observed in AS and nr-axSpA subpopulations and improvements with CZP were maintained to Wk96. Conclusions Compared with placebo, treatment with CZP significantly improved work and household productivity and resulted in greater social participation for patients with axSpA, which could lead to considerable indirect cost gains. Trial registration number NCT01087762. PMID:29670761

Association of human leukocyte A, B, and DR antigens in Colombian patients with diagnosis of spondyloarthritis.

PubMed

Santos, Ana M; Peña, Paola; Avila, Mabel; Briceño, Ignacio; Jaramillo, Carlos; Vargas-Alarcon, Gilberto; Rueda, Juan C; Saldarriaga, Eugenia-Lucia; Angarita, Jose-Ignacio; Martinez-Rodriguez, Nancy; Londono, John

2017-04-01

There is substantial evidence that non-B27 major histocompatibility complex (MHC) genes are associated with spondyloarthritis (SpA). Studies in Mexican and Tunisian populations demonstrated the association of SpA and human leukocyte antigen (HLA) B15. The purpose of this study was to evaluate the association of HLA-A, B, and DR antigens in a group of Colombian patients with a diagnosis of SpA. A total of 189 patients and 100 healthy subjects were included in the present study. All subjects underwent a complete characterization of HLA alleles A, B, and DR. Of the 189 studied patients, 35 were reactive arthritis (ReA), 87 were ankylosing spondylitis (AS), and 67 undifferentiated SpA (uSpA). According to the Assessment of Spondyloarthritis International Society (ASAS) criteria, 167 were axial SpA (axSpA) and 171 were peripheral SpA (pSpA). 63.8% were men, with a mean age of 35.9 ± 12.7 years. 40.7% (77/189) of patients were HLA-B27 positive of which 52.9% had AS and 42.5% axSpA. 23.2% (44/189) of patients were HLA-B15 positive: 23.8% were uSpA, 12.57% were axSpA, and 11.7% were pSpA. In addition, HLA-DRB1*01 was associated with AS (58.6%) and axSpA (42.5%). Also, HLA-DRB1*04 was present in 62 patients with AS (71.2%) and in 26 with axSpA (15.5%). In this population, we found a strong association between the presence of HLA-B27 and the diagnosis of axSpA and AS, but the HLA-B15 is also significantly associated with all subtypes of the disease, predominantly with pSpA. Additionally, HLA-DR1 and DR4 were associated in a cohort of patients with SpA from Colombia.

Activation of WIP1 Phosphatase by HTLV-1 Tax Mitigates the Cellular Response to DNA Damage

PubMed Central

Dayaram, Tajhal; Lemoine, Francene J.; Donehower, Lawrence A.; Marriott, Susan J.

2013-01-01

Genomic instability stemming from dysregulation of cell cycle checkpoints and DNA damage response (DDR) is a common feature of many cancers. The cancer adult T cell leukemia (ATL) can occur in individuals infected with human T cell leukemia virus type 1 (HTLV-1), and ATL cells contain extensive chromosomal abnormalities, suggesting that they have defects in the recognition or repair of DNA damage. Since Tax is the transforming protein encoded by HTLV-1, we asked whether Tax can affect cell cycle checkpoints and the DDR. Using a combination of flow cytometry and DNA repair assays we showed that Tax-expressing cells exit G1 phase and initiate DNA replication prematurely following damage. Reduced phosphorylation of H2AX (γH2AX) and RPA2, phosphoproteins that are essential to properly initiate the DDR, was also observed in Tax-expressing cells. To determine the cause of decreased DDR protein phosphorylation in Tax-expressing cells, we examined the cellular phosphatase, WIP1, which is known to dephosphorylate γH2AX. We found that Tax can interact with Wip1 in vivo and in vitro, and that Tax-expressing cells display elevated levels of Wip1 mRNA. In vitro phosphatase assays showed that Tax can enhance Wip1 activity on a γH2AX peptide target by 2-fold. Thus, loss of γH2AX in vivo could be due, in part, to increased expression and activity of WIP1 in the presence of Tax. siRNA knockdown of WIP1 in Tax-expressing cells rescued γH2AX in response to damage, confirming the role of WIP1 in the DDR. These studies demonstrate that Tax can disengage the G1/S checkpoint by enhancing WIP1 activity, resulting in reduced DDR. Premature G1 exit of Tax-expressing cells in the presence of DNA lesions creates an environment that tolerates incorporation of random mutations into the host genome. PMID:23405243

Positive correlation between inflammation on sacroiliac joint MRI and serum C-terminal telopeptide of type-I collagen in ankylosing spondylitis but not in non-radiographic axial spondyloarthritis.

PubMed

Kang, Kwi Young; Jung, Joon-Yong; Hong, Yeon Sik; Ju, Ji Hyeon; Park, Sung-Hwan

2017-01-01

To identify the clinical disease activity scores and laboratory markers that best reflect magnetic resonance imaging (MRI)-determined sacroiliac joint (SIJ) inflammation in ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). This cross-sectional study included all consecutive patients who presented with axial spondyloarthritis in 2013-2015. All underwent SIJ MRI. The bone marrow oedema in the inflammatory lesions on MRI was scored using the SPondyloArthritis Research Consortium of Canada (SPARCC) method. Bone-specific alkaline phosphatase (BALP), serum C-terminal telopeptide of type-I collagen (sCTX-I), and inflammatory markers were measured. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) were assessed. The correlations between the MRI-determined SIJ inflammation scores and disease activity scores and laboratory variables were evaluated. Of the 81 patients with axSpA, 45 had AS and 36 had nr-axSpA. The AS and nr-axSpA groups did not differ in terms of disease activity scores, physical functional index, or MRI-determined SIJ inflammation. Erythrocyte sedimentation rate, C-reactive protein, and ASDAS correlated with MRI inflammatory scores in nr-axSpA but not in AS. sCTX-I correlated with MRI-determined SIJ inflammatory scores in AS only. BASDAI and BALP levels did not associate with MRI inflammatory scores in either group. Multivariate analysis showed that sCTX-I associated independently with MRI inflammatory score in AS (β=17.047, p=0.038). Inflammatory markers and ASDAS correlated with active sacroiliitis on MRI in nr-axSpA only. In AS, only sCTX-I correlated with active inflammation on SIJ MRI. sCTX-I may be useful as a marker of objective inflammation in AS.

Rac1 Protein Signaling Is Required for DNA Damage Response Stimulated by Topoisomerase II Poisons*

PubMed Central

Huelsenbeck, Stefanie C.; Schorr, Anne; Roos, Wynand P.; Huelsenbeck, Johannes; Henninger, Christian; Kaina, Bernd; Fritz, Gerhard

2012-01-01

To investigate the potency of the topoisomerase II (topo II) poisons doxorubicin and etoposide to stimulate the DNA damage response (DDR), S139 phosphorylation of histone H2AX (γH2AX) was analyzed using rat cardiomyoblast cells (H9c2). Etoposide caused a dose-dependent increase in the γH2AX level as shown by Western blotting. By contrast, the doxorubicin response was bell-shaped with high doses failing to increase H2AX phosphorylation. Identical results were obtained by immunohistochemical analysis of γH2AX focus formation, comet assay-based DNA strand break analysis, and measuring the formation of the topo II-DNA cleavable complex. At low dose, doxorubicin activated ataxia telangiectasia mutated (ATM) but not ATM and Rad3-related (ATR). Both the lipid-lowering drug lovastatin and the Rac1-specific inhibitor NSC23766 attenuated doxorubicin- and etoposide-stimulated H2AX phosphorylation, induction of DNA strand breaks, and topo II-DNA complex formation. Lovastatin and NSC23766 acted in an additive manner. They did not attenuate doxorubicin-induced increase in p-ATM and p-Chk2 levels. DDR stimulated by topo II poisons was partially blocked by inhibition of type I p21-associated kinases. DDR evoked by the topoisomerase I poison topotecan remained unaffected by lovastatin. The data show that the mechanisms involved in DDR stimulated by topo II poisons are agent-specific with anthracyclines lacking DDR-stimulating activity at high doses. Pharmacological inhibition of Rac1 signaling counteracts doxorubicin- and etoposide-stimulated DDR by disabling the formation of the topo II-DNA cleavable complex. Based on the data we suggest that Rac1-regulated mechanisms are required for DNA damage induction and subsequent activation of the DDR following treatment with topo II but not topo I poisons. PMID:23012366

Rac1 protein signaling is required for DNA damage response stimulated by topoisomerase II poisons.

PubMed

Huelsenbeck, Stefanie C; Schorr, Anne; Roos, Wynand P; Huelsenbeck, Johannes; Henninger, Christian; Kaina, Bernd; Fritz, Gerhard

2012-11-09

To investigate the potency of the topoisomerase II (topo II) poisons doxorubicin and etoposide to stimulate the DNA damage response (DDR), S139 phosphorylation of histone H2AX (γH2AX) was analyzed using rat cardiomyoblast cells (H9c2). Etoposide caused a dose-dependent increase in the γH2AX level as shown by Western blotting. By contrast, the doxorubicin response was bell-shaped with high doses failing to increase H2AX phosphorylation. Identical results were obtained by immunohistochemical analysis of γH2AX focus formation, comet assay-based DNA strand break analysis, and measuring the formation of the topo II-DNA cleavable complex. At low dose, doxorubicin activated ataxia telangiectasia mutated (ATM) but not ATM and Rad3-related (ATR). Both the lipid-lowering drug lovastatin and the Rac1-specific inhibitor NSC23766 attenuated doxorubicin- and etoposide-stimulated H2AX phosphorylation, induction of DNA strand breaks, and topo II-DNA complex formation. Lovastatin and NSC23766 acted in an additive manner. They did not attenuate doxorubicin-induced increase in p-ATM and p-Chk2 levels. DDR stimulated by topo II poisons was partially blocked by inhibition of type I p21-associated kinases. DDR evoked by the topoisomerase I poison topotecan remained unaffected by lovastatin. The data show that the mechanisms involved in DDR stimulated by topo II poisons are agent-specific with anthracyclines lacking DDR-stimulating activity at high doses. Pharmacological inhibition of Rac1 signaling counteracts doxorubicin- and etoposide-stimulated DDR by disabling the formation of the topo II-DNA cleavable complex. Based on the data we suggest that Rac1-regulated mechanisms are required for DNA damage induction and subsequent activation of the DDR following treatment with topo II but not topo I poisons.

Performance Evaluation of the ONR Axial Waterjet 2 (AxWJ-2)

DTIC Science & Technology

2009-12-01

regions of the blade wakes and near the wall. Pump curves In order to estimate the uncertainty on the measured pump performance, it was first necessary to...velocity well outside the hub wake , but the tangential velocity magnitude and the axial velocity wake deficit are overpredicted near the hub. The...of these plots consists of a grid of 55 * 1024 points. In all three plots, the low-velocity regions six blade wakes are clearly visible, as are the

Performances of One-Round Walks in Linear Congestion Games

NASA Astrophysics Data System (ADS)

Bilò, Vittorio; Fanelli, Angelo; Flammini, Michele; Moscardelli, Luca

We investigate the approximation ratio of the solutions achieved after a one-round walk in linear congestion games. We consider the social functions {Stextsc{um}}, defined as the sum of the players’ costs, and {Mtextsc{ax}}, defined as the maximum cost per player, as a measure of the quality of a given solution. For the social function {Stextsc{um}} and one-round walks starting from the empty strategy profile, we close the gap between the upper bound of 2+sqrt{5}≈ 4.24 given in [8] and the lower bound of 4 derived in [4] by providing a matching lower bound whose construction and analysis require non-trivial arguments. For the social function {Mtextsc{ax}}, for which, to the best of our knowledge, no results were known prior to this work, we show an approximation ratio of Θ(sqrt[4]{n^3}) (resp. Θ(nsqrt{n})), where n is the number of players, for one-round walks starting from the empty (resp. an arbitrary) strategy profile.

Optimization of shallow arches against instability using sensitivity derivatives

NASA Technical Reports Server (NTRS)

Kamat, Manohar P.

1987-01-01

The author discusses the problem of optimization of shallow frame structures which involve a coupling of axial and bending responses. A shallow arch of a given shape and of given weight is optimized such that its limit point load is maximized. The cross-sectional area, A(x) and the moment of inertia, I(x) of the arch obey the relationship I(x) = rho A(x) sup n, n = 1,2,3 and rho is a specified constant. Analysis of the arch for its limit point calculation involves a geometric nonlinear analysis which is performed using a corotational formulation. The optimization is carried out using a second-order projected Lagrangian algorithm and the sensitivity derivatives of the critical load parameter with respect to the areas of the finite elements of the arch are calculated using implicit differentation. Results are presented for an arch of a specified rise to span ratio under two different loadings and the limitations of the approach for the intermediate rise arches are addressed.

Movement characteristics of persons with prader-willi syndrome rising from supine.

PubMed

Belt, A B; Hertel, T A; Mante, J R; Marks, T; Rockett, V L; Wade, C; Clayton-Krasinski, D

2001-01-01

The purposes of this study were to: 1) determine if previously published descriptors of the supine to stand rising task in healthy individuals could be applied to the movements of persons with Prader-Willi Syndrome (PWS); and 2) assess upper extremity (UE), axial region (AX), and lower extremity (LE) movements among subjects with PWS compared with controls. Nine subjects with PWS (seven-36 years of age) and matched controls were videotaped performing 10 rising trials. The UE, AX, and LE movements were classified using published descriptors. Occurrence frequencies of movement patterns, duration of movement, and the relationships among body region movement score, BMI, and age were determined. Subjects with PWS utilized developmentally less advanced asymmetrical rising patterns, took longer to rise, and demonstrated less within subject variability than controls. Categorical descriptors, with minor modifications, can be used to describe rising movements in persons with PWS. Knowledge of successful rising patterns may assist PTs when examining or planning intervention strategies for teaching the rising task.

An Algebraic Approach for Solving Quadratic Inequalities

ERIC Educational Resources Information Center

Mahmood, Munir; Al-Mirbati, Rudaina

2017-01-01

In recent years most text books utilise either the sign chart or graphing functions in order to solve a quadratic inequality of the form ax[superscript 2] + bx + c < 0 This article demonstrates an algebraic approach to solve the above inequality. To solve a quadratic inequality in the form of ax[superscript 2] + bx + c < 0 or in the…

Supporting document for the historical tank content estimate for AX-tank farm

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

Brevick, C.H., Westinghouse Hanford

This Supporting Document provides historical in-depth characterization information on AX-Tank Farm, such as historical waste transfer and level data, tank physical information,temperature plots, liquid observation well plots, chemical analyte and radionuclide inventories for the Historical Tank Content Estimate Report for the northeast quadrant of the Hanford 200 East Area.

Economic decision-making in morning/evening-type people as a function of time of day.

PubMed

Correa, Angel; Ruiz-Herrera, Noelia; Ruz, Maria; Tonetti, Lorenzo; Martoni, Monica; Fabbri, Marco; Natale, Vincenzo

2017-01-01

Decision-making is affected by psychological factors like emotional state or cognitive control, which may also vary with circadian rhythmicity. Here, we tested the influence of chronotype (32 morning-type versus 32 evening-type) and time of day (9 a.m. versus 5 p.m.) on interpersonal decision-making as measured by the Ultimatum Game. Participants had to accept or reject different economic offers proposed by a virtual participant. Acceptance involved distribution of gains as proposed, whereas rejection resulted in no gain for either player. The results of the game showed a deviation from rational performance, as participants usually rejected the unfair offers. This behaviour was similar for both chronotype groups, and in both times of day. This result may reflect the robustness of decision-making strategies across standard circadian phases under ecological conditions. Furthermore, morning-types invested more time than evening-types to respond to high-uncertainty offers. This more cautious decision-making style of morning-types fits with our finding of higher proactive control as compared to evening-types when performing the AX-Continuous Performance Task. In line with the literature on personality traits, our results suggest that morning-types behave with more conscientiousness and less risk-taking than evening-type individuals.

Modeling the User for Education, Training, and Performance Aiding

DTIC Science & Technology

2004-04-01

It is a fact both obvious and frequently neglected that human competence, which is a product of human cognition, is essential to every military...approach has been called an instructional imperative and an economic impossibility. It would be maximally effective but remains unaffordable because...based on reflection) all producing different perceptual, memory, and motor functions. ( Sloman , 2001; 2003) (http://www.cs.b ham.ac.uk/~axs

Development of Web tools to predict axillary lymph node metastasis and pathological response to neoadjuvant chemotherapy in breast cancer patients.

PubMed

Sugimoto, Masahiro; Takada, Masahiro; Toi, Masakazu

2014-12-09

Nomograms are a standard computational tool to predict the likelihood of an outcome using multiple available patient features. We have developed a more powerful data mining methodology, to predict axillary lymph node (AxLN) metastasis and response to neoadjuvant chemotherapy (NAC) in primary breast cancer patients. We developed websites to use these tools. The tools calculate the probability of AxLN metastasis (AxLN model) and pathological complete response to NAC (NAC model). As a calculation algorithm, we employed a decision tree-based prediction model known as the alternative decision tree (ADTree), which is an analog development of if-then type decision trees. An ensemble technique was used to combine multiple ADTree predictions, resulting in higher generalization abilities and robustness against missing values. The AxLN model was developed with training datasets (n=148) and test datasets (n=143), and validated using an independent cohort (n=174), yielding an area under the receiver operating characteristic curve (AUC) of 0.768. The NAC model was developed and validated with n=150 and n=173 datasets from a randomized controlled trial, yielding an AUC of 0.787. AxLN and NAC models require users to input up to 17 and 16 variables, respectively. These include pathological features, including human epidermal growth factor receptor 2 (HER2) status and imaging findings. Each input variable has an option of "unknown," to facilitate prediction for cases with missing values. The websites developed facilitate the use of these tools, and serve as a database for accumulating new datasets.

General practitioners' perceptions of their ability to identify and refer patients with suspected axial spondyloarthritis: a qualitative study.

PubMed

van Onna, Marloes; Gorter, Simone; van Meerendonk, Aniek; van Tubergen, Astrid

2014-05-01

To explore the knowledge, beliefs, and experiences of general practitioners (GP) about inflammatory back pain (IBP) and axial spondyloarthritis (axSpA) and potential barriers for referral of patients suspected of having axSpA. A qualitative study involving semistructured interviews with GP was conducted. Transcripts of the interviews were independently read and annotated by 2 readers. Illustrative themes were identified and a coding system to categorize the data was developed. Ten GP (all men; mean age 49 yrs) were interviewed. All could adequately describe "classic" ankylosing spondylitis (AS) and mentioned chronic back pain and/or stiffness as key features. All GP thought that AS is almost exclusively diagnosed in men. Six GP knew that there is a difference between mechanical back pain and IBP, but could recall only a limited number of variables indicative of IBP, such as awakening night pain (4 GP), insidious onset of back pain (1 GP), improvement with movement (1 GP), and (morning) stiffness (2 GP). Two GP mentioned peripheral arthritis as other SpA features, none mentioned dactylitis or enthesitis. GP awareness of associated extraarticular manifestations was low. Most GP expressed that (practical) referral measures would be useful. GP are aware of "classic", but longterm features of axSpA. Knowledge about the disease spectrum and early detection is, however, limited. Addressing these issues in training programs may improve recognition of axSpA in primary care. This may ultimately contribute to earlier referral, diagnosis, and initiation of effective treatment in patients with axSpA.

Apigenin induces DNA damage through the PKCδ-dependent activation of ATM and H2AX causing down-regulation of genes involved in cell cycle control and DNA repair

PubMed Central

Arango, Daniel; Parihar, Arti; Villamena, Frederick A.; Wang, Liwen; Freitas, Michael A.; Grotewold, Erich; Doseff, Andrea I.

2014-01-01

Apigenin, an abundant plant flavonoid, exhibits anti-proliferative and anti-carcinogenic activities through mechanisms yet not fully defined. In the present study, we show that the treatment of leukemia cells with apigenin resulted in the induction of DNA damage preceding the activation of the apoptotic program. Apigenin-induced DNA damage was mediated by p38 and protein kinase C-delta (PKCδ), yet was independent of reactive oxygen species or caspase activity. Treatment of monocytic leukemia cells with apigenin induced the phosphorylation of the ataxia-telangiectasia mutated (ATM) kinase and histone H2AX, two key regulators of the DNA damage response, without affecting the ataxia-telangiectasia mutated and Rad-3-related (ATR) kinase. Silencing and pharmacological inhibition of PKCδ abrogated ATM and H2AX phosphorylation, whereas inhibition of p38 reduced H2AX phosphorylation independently of ATM. We established that apigenin delayed cell cycle progression at G1/S and increased the number of apoptotic cells. In addition, genome-wide mRNA analyses showed that apigenin-induced DNA damage led to down-regulation of genes involved in cell-cycle control and DNA repair. Taken together, the present results show that the PKCδ-dependent activation of ATM and H2AX define the signaling networks responsible for the regulation of DNA damage promoting genome-wide mRNA alterations that result in cell cycle arrest, hence contributing to the anti-carcinogenic activities of this flavonoid. PMID:22985621

Efficacy of high intensity exercise on disease activity and cardiovascular risk in active axial spondyloarthritis: a randomized controlled pilot study.

PubMed

Sveaas, Silje Halvorsen; Berg, Inger Jorid; Provan, Sella Aarrestad; Semb, Anne Grete; Hagen, Kåre Birger; Vøllestad, Nina; Fongen, Camilla; Olsen, Inge C; Michelsen, Annika; Ueland, Thor; Aukrust, Pål; Kvien, Tore K; Dagfinrud, Hanne

2014-01-01

Physical therapy is recommended for the management of axial spondyloarthritis (axSpA) and flexibility exercises have traditionally been the main focus. Cardiovascular (CV) diseases are considered as a major health concern in axSpA and there is strong evidence that endurance and strength exercise protects against CV diseases. Therefore, the aim of this study was to investigate the efficacy of high intensity endurance and strength exercise on disease activity and CV health in patients with active axSpA. In a single blinded randomized controlled pilot study the exercise group (EG) performed 12 weeks of endurance and strength exercise while the control group (CG) received treatment as usual. The primary outcome was the Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS). Secondary outcomes included patient reported disease activity (Bath AS Disease Activity Index [BASDAI]), physical function (Bath AS Functional Index [BASFI]), and CV risk factors measured by arterial stiffness (Augmentation Index [Alx]) and Pulse Wave Velocity [PWV]), cardiorespiratory fitness (VO2 peak) and body composition. ANCOVA on the post intervention values with baseline values as covariates was used to assess group differences, and Mann Whitney U-test was used for outcomes with skewed residuals. Twenty-eight patients were included and 24 (EG, n = 10, CG, n = 14) completed the study. A mean treatment effect of -0.7 (95%CI: -1.4, 0.1) was seen in ASDAS score. Treatment effects were also observed in secondary outcomes (mean group difference [95%CI]): BASDAI: -2.0 (-3.6, -0.4), BASFI: -1.4 (-2.6, -0.3), arterial stiffness (estimated median group differences [95% CI]): AIx (%): -5.3 (-11.0, -0.5), and for PVW (m/s): -0.3 (-0.7, 0.0), VO2 peak (ml/kg/min) (mean group difference [95%CI]: 3.7 (2.1, 5.2) and trunk fat (%): -1.8 (-3.0, -0.6). No adverse events occurred. High intensity exercise improved disease activity and reduced CV risk factors in patients with active axSpA. These effects will be further explored in a larger trial. ClinicalTrials.gov NCT01436942.

Which aspects of health are most important for patients with spondyloarthritis? A Best Worst Scaling based on the ASAS Health Index.

PubMed

Kiltz, Uta; Essers, Ivette; Hiligsmann, Mickael; Braun, Juergen; Maksymowych, Walter P; Taylor, William J; van der Heijde, Désirée; Boonen, Annelies

2016-10-01

The aim was to investigate the importance of aspects of health for patients with axial SpA (axSpA) and to explore differences across different subgroups. A Best Worst Scaling exercise was conducted in patients with axSpA from 20 countries (10 patients per country) worldwide. Using the 17 items of the Assessment of SpondyloArthritis international Society Health Index, a set of 17 choice tasks was generated. Patients had to indicate in each choice task the most and least important out of four varying items. The hierarchical Bayes method was used to estimate the relative importance score for each item (summing to 100). Subgroup comparisons were performed for relevant demographic (gender, age, work status, geographical area and education) and disease characteristics (SpA phenotype, disease duration and disease activity) using one-way analysis of variance or the Mann-Whitney U-test. The experiment was completed by 199 patients with axSpA [117 (58.8%) men, mean (sd) age 42.3 (13.6) years, mean (sd) disease duration 11.1 (11.2) years, 130 (65.3%) AS]. The highest relative importance was assigned to pain (14.2; 95% CI: 13.8, 14.6), sleep (10.3; 95% CI: 9.6, 11.0), being exhausted (9.6; 95% CI: 9.0, 10.3), standing (9.25; 95% CI: 8.5, 10.0) and motivation to do anything that requires physical effort (8.7; 95% CI: 8.1, 9.3). The lowest relative importance was assigned to sexual relationships, toileting, contact with people, driving and washing hair. Differences between subgroups were small or in aspects with lower importance. A clear gradient was seen in the importance of the different aspects of health that impact functioning of patients with axSpA. Differences between subgroups were small or non-existent. These findings help to align clinical care to patients' needs. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sensitive immunodetection of radiotoxicity after iodine-131 therapy for thyroid cancer using γ-H2AX foci of DNA damage in lymphocytes.

PubMed

Doai, Mariko; Watanabe, Naoto; Takahashi, Tomoko; Taniguchi, Mitsuru; Tonami, Hisao; Iwabuchi, Kuniyoshi; Kayano, Daiki; Fukuoka, Makoto; Kinuya, Seigo

2013-04-01

The purpose of our study was to evaluate the degree of radiotoxicity to lymphocytes in thyroid cancer after iodine-131(I-131) therapy using γ-H2AX foci immunodetection. This study focused on 15 patients who underwent I-131 therapy for differentiated thyroid cancer after surgery. All patients received 3.7 GBq of I-131. Venous blood samples were collected from each patient before therapy and 4 days thereafter. Lymphocytes were isolated from the blood samples and subjected to γ-H2AX immunofluorescence staining. The number (mean ± SD) of foci per lymphocyte nucleus was 0.41 ± 0.51 before and 6.19 ± 1.80 after radioiodine therapy, and this difference was statistically significant (P = 0.001 < 0.05). Absorbed doses estimated for the 15 patients were 0.77 ± 0.31 Gy applying standard line in vitro external radiation doses. γ-H2AX foci immunodetection in lymphocytes may detect radiation-induced DNA damage associated with I-131 therapy for thyroid cancer, and may facilitate estimation of the radiation doses absorbed with this therapy.

Changes in molecular characteristics of cereal carbohydrates after processing and digestion.

PubMed

Kasprzak, Mirosław Marek; Lærke, Helle Nygaard; Knudsen, Knud Erik Bach

2012-12-10

Different extraction, purification and digestion methods were used to investigate the molecular properties of carbohydrates in arabinoxylan and β-glucan concentrates, dietary fiber (DF) rich breads and ileum content of bread fed pigs. The breads studied were: a low DF wheat bread (WF), whole meal rye bread (GR), rye bread with kernels (RK), wheat bread supplemented with wheat arabinoxylan concentrate (AX) and wheat bread supplemented with oat β-glucan concentrate (BG). The weight average molecular weight (M(w)) of extractable carbohydrates in β-glucan concentrate decreased eight-fold after inclusion in the BG bread when exposed to in vitro digestion, while the M(w) of purified extractable carbohydrates in AX bread was reduced two-fold, and remained almost unaffected until reaching the terminal ileum of pigs. Similarly, the M(w) of purified extractable carbohydrates in GR and RK bread was not significantly changed in the ileum. The AX bread resulted in the highest concentration of dissolved arabinoxylan in the ileum among all the breads that caused a substantial increased in ileal AX viscosity. Nevertheless, for none of the breads, the M(w) of extractable carbohydrates was related neither to the bread extract nor ileal viscosity.

Easy fix for clinical laboratories for the false-positive defect with the Abbott AxSym total beta-hCG test.

PubMed

Cole, Laurence A; Khanlian, Sarah A

2004-05-01

False-positive hCG results can lead to erroneous diagnoses and needless chemotherapy and surgery. In the last 2 years, eight publications described cases involving false-positive hCG tests; all eight involved the AxSym test. We investigated the source of this abundance of cases and a simple fix that may be used by clinical laboratories. False-positive hCG was primarily identified by absence of hCG in urine and varying or negative hCG results in alternative tests. Seventeen false-positive serum samples in the AxSym test were evaluated undiluted and at twofold dilution with diluent containing excess goat serum or immunoglobulin. We identified 58 patients with false-positive hCG, 47 of 58 due to the Abbott AxSym total hCGbeta test (81%). Sixteen of 17 of these "false-positive" results (mean 100 mIU/ml) became undetectable when tested again after twofold dilution. A simple twofold dilution with this diluent containing excess goat serum or immunoglobulin completely protected 16 of 17 samples from patients having false-positive results. It is recommended that laboratories using this test use twofold dilution as a minimum to prevent false-positive results.

Expediting Combinatorial Data Set Analysis by Combining Human and Algorithmic Analysis.

PubMed

Stein, Helge Sören; Jiao, Sally; Ludwig, Alfred

2017-01-09

A challenge in combinatorial materials science remains the efficient analysis of X-ray diffraction (XRD) data and its correlation to functional properties. Rapid identification of phase-regions and proper assignment of corresponding crystal structures is necessary to keep pace with the improved methods for synthesizing and characterizing materials libraries. Therefore, a new modular software called htAx (high-throughput analysis of X-ray and functional properties data) is presented that couples human intelligence tasks used for "ground-truth" phase-region identification with subsequent unbiased verification by an algorithm to efficiently analyze which phases are present in a materials library. Identified phases and phase-regions may then be correlated to functional properties in an expedited manner. For the functionality of htAx to be proven, two previously published XRD benchmark data sets of the materials systems Al-Cr-Fe-O and Ni-Ti-Cu are analyzed by htAx. The analysis of ∼1000 XRD patterns takes less than 1 day with htAx. The proposed method reliably identifies phase-region boundaries and robustly identifies multiphase structures. The method also addresses the problem of identifying regions with previously unpublished crystal structures using a special daisy ternary plot.

Biologics for treating axial spondyloarthritis.

PubMed

Jones, Alexis; Ciurtin, Coziana; Ismajli, Mediola; Leandro, Maria; Sengupta, Raj; Machado, Pedro M

2018-06-01

Spondyloarthritis (SpA) encompasses a heterogeneous group of diseases sharing genetic, immunological, clinical and imaging features. Axial spondyloarthritis (axSpA) refers to a subgroup characterised predominately by inflammation of the axial skeleton with subsequent symptoms of chronic (often inflammatory) back pain and sacroiliitis. There is a strong association with the major histocompatibility complex (MHC) class I allele human leukocyte antigen (HLA) B27. In the last decade, there has been significant progress in earlier detection of the disease and the molecular mechanisms involved in its pathogenesis. The subsequent introduction of anti-tumour necrosis factor (TNF) has revolutionised the treatment of patients with axSpA. Areas covered: In this article, we review the current biologic therapies for axSpA, the emergence of biosimilars, predictors of response, primary and secondary failure and new biologics on the horizon. Expert opinion: There have been significant advances in the treatment of axSpA. Beyond the clear efficacy of anti-TNF inhibition, IL-17 offers an alternative therapeutic target and there is promise from inhibition of the IL-17/IL-23 pathway and small molecules, such as Janus kinase (JAK) inhibitors. Biosimilars have offered greater affordability and choice within this increasingly growing field of therapeutics.

Changes in Molecular Characteristics of Cereal Carbohydrates after Processing and Digestion

PubMed Central

Kasprzak, Mirosław Marek; Lærke, Helle Nygaard; Knudsen, Knud Erik Bach

2012-01-01

Different extraction, purification and digestion methods were used to investigate the molecular properties of carbohydrates in arabinoxylan and β-glucan concentrates, dietary fiber (DF) rich breads and ileum content of bread fed pigs. The breads studied were: a low DF wheat bread (WF), whole meal rye bread (GR), rye bread with kernels (RK), wheat bread supplemented with wheat arabinoxylan concentrate (AX) and wheat bread supplemented with oat β-glucan concentrate (BG). The weight average molecular weight (Mw) of extractable carbohydrates in β-glucan concentrate decreased eight-fold after inclusion in the BG bread when exposed to in vitro digestion, while the Mw of purified extractable carbohydrates in AX bread was reduced two-fold, and remained almost unaffected until reaching the terminal ileum of pigs. Similarly, the Mw of purified extractable carbohydrates in GR and RK bread was not significantly changed in the ileum. The AX bread resulted in the highest concentration of dissolved arabinoxylan in the ileum among all the breads that caused a substantial increased in ileal AX viscosity. Nevertheless, for none of the breads, the Mw of extractable carbohydrates was related neither to the bread extract nor ileal viscosity. PMID:23222731

AxIOM: Amphipod crustaceans from insular Posidonia oceanica seagrass meadows

PubMed Central

Heughebaert, André; Lepoint, Gilles

2016-01-01

Abstract Background The Neptune grass, Posidonia oceanica (L.) Delile, 1813, is the most widespread seagrass of the Mediterranean Sea. This foundation species forms large meadows that, through habitat and trophic services, act as biodiversity hotspots. In Neptune grass meadows, amphipod crustaceans are one of the dominant groups of vagile invertebrates, forming an abundant and diverse taxocenosis. They are key ecological components of the complex, pivotal, yet critically endangered Neptune grass ecosystems. Nevertheless, comprehensive qualitative and quantitative data about amphipod fauna found in Mediterranean Neptune grass meadows remain scarce, especially in insular locations. New information Here, we provide in-depth metadata about AxIOM, a sample-based dataset published on the GBIF portal. AxIOM is based on an extensive and spatially hierarchized sampling design with multiple years, seasons, day periods, and methods. Samples were taken along the coasts of Calvi Bay (Corsica, France) and of the Tavolara-Punta Coda Cavallo Marine Protected Area (Sardinia, Italy). In total, AxIOM contains 187 samples documenting occurrence (1775 records) and abundance (10720 specimens) of amphipod crustaceans belonging to 72 species spanning 29 families. The dataset is available at http://ipt.biodiversity.be/resource?r=axiom. PMID:27660521

Geolocation Via Satellite: A Methodology and Error Analysis

DTIC Science & Technology

1988-05-01

o - sing cow0o sinoo (4.449) acoso = in a... ! (4.44b) asin1 _ acos = 0 (4.45) ax0 No0 2!!LO- = -cso sinI sinvo (4.46a) 89coso = io5s (4.46b) avo...CS6 av0 asinO = o (4.47a) acoso snocs (4.47b) asina = siflA acoso (4.48a) a9cosA - i + COS sin - sinqS0 asino aoo O-So COSOO c s sb aoo -COSA a9coso...4.48b) asinb __ cosa= 0 (4.49) ax0 ax0 asinA =_ sifl cosv - sinA acoso (4.50a) av0 cos OS v aCoSA CSflOO OS fl4o COSA ao ~ (4.50b) (9os acs a 0 * o4

Exercise-induced airway obstruction in young asthmatics measured by impulse oscillometry.

PubMed

Lee, J H; Lee, Y W; Shin, Y S; Jung, Y H; Hong, C S; Park, J W

2010-01-01

Impulse oscillometry (IOS) is a good method for measuring airway resistance. It does not require special breathing skills and it can reflect different aspects of airway obstruction to those revealed by spirometry, which is an effort-dependent maneuver. To evaluate the characteristics of airway obstruction in young asthmatics after an exercise bronchial provocation test (EBPT) using IOS. Forty-seven young adults were enrolled in the study. All the participants underwent a methacholine bronchial provocation test (MBPT) and an EBPT for the evaluation of their asthma. IOS and spirometric parameters were collected at baseline and at 0, 5, 10, 20, and 30 minutes post-EBPT.The participants were divided into 2 groups according to MBPT positivity: an airway hyperresponsiveness (AHR) group and a no-AHR group. There were differences in the percent decrease in forced expiratory volume in the first second (FEV1) between the 2 groups at 5, 10, and 20 minutes after exercise. Resistance at 5 Hz (R5) increased in the AHR group but not in the no-AHR group at 5 and 10 minutes after exercise. Integration of reactance from 5 Hz to resonance frequency (area of reactance, AX) was also increased in the AHR group at only 5 and 10 minutes post-EBPT. Delta R5 and delta AX at 5 and 10 minutes post-exercise were well correlated with the percent decrease in FEV1. IOS parameters, especially delta R5 and delta AX, may be useful for performing objective evaluations and improving our understanding of exercise-induced airway obstruction in young asthmatics.

Decrease of selective immunoglobulin E response to amoxicillin despite repeated administration of benzylpenicillin and penicillin V.

PubMed

Fernandez, T; Torres, M J; R-Pena, R; Fuentes, M S; Robles, S; Mayorga, C; Blanca, M

2005-12-01

Subjects with IgE responses to betalactams can develop selective or cross-reactive responses after the administration of penicillin derivatives. After the reaction, however, the hapten induces a boosting phenomenon, which may increase the titre and the affinity of the antibody, with the resulting risk of developing allergic reactions to other penicillins. To determine in subjects with selective responses to amoxicillin (AX) and good tolerance to benzylpenicillin (BP) and penicillin V (PV) whether the administration of these compounds induced any change in specificity, measured by either skin or in vitro testing, which could predict the appearance of cross-reactivity. Ten subjects with a selective response to AX were followed-up for 2 years with the periodic administration of penicillin G and V (Group A) and compared with another group composed of 10 persons with identical clinical characteristics but without repeated penicillin administration (Group B). Periodic in vitro and in vivo measurements of specific IgE antibodies were performed at 6-month intervals. Patients were randomized to Group A or B according to their order of inclusion. In both groups, skin test reactivity tended to decrease, and although greater in Group A, the difference was not significant compared with Group B. Median RAST values also decreased over time and showed no differences in the exposed group compared with the controls. One patient in Group A became positive to benzylpenicilloyl (BPO), despite becoming negative to AX. Subjects with selective IgE responses to side-chain-specific determinants seem to become negative, with no influence from subsequent administration of a closely related penicillin.

The movement patterns used to rise from a supine position by children with developmental delay and age-related differences in these.

PubMed

Hsue, Bih-Jen; Wang, Yun-Er; Chen, Yung-Jung

2014-09-01

The purposes of this study were to determine (1) movement patterns and strategies of children with mild to moderate developmental delay (DD) used to rise up and how they differ from those used by age-matched children with typical development (TD), (2) whether the movement patterns differ with age in children with DD, and (3) to determine the developmental sequences for the UE, AX and LE in children with DD and whether they are different from those used by children with TD. Sixty six children with TD and 31 children with DD aged two to six years were recruited. Peabody Developmental Motor Scale II (PDMS-2) was used to determine the motor performance level. The participants were recorded during rising for at least five repetitions. Two trained pediatric physical therapists viewed each video recording and classified the movement patterns of the upper extremities (UE), trunk/axial (AX) and lower extremities (LE) regions using descriptive categories developed by previous researchers. The DD and TD groups were further divided into four subgroups each using a one-year interval. The percentage of occurrence of the each UE, AX and LE movement was determined and compared across subgroups, and between each age-matched pair of TD and DD groups. The results demonstrated that the participants in the TD group clearly followed the proposed developmental sequence and the children with DD followed the developmental sequences but with different maturation speeds and greater variability, especially at the age of three to five years. The most common movement patterns used by the children in each of the DD subgroups were at least one developmental categorical pattern behind those used by the age-matched children with TD before five years old, except for the LE region. In the DD group, the movement patterns had moderate to high correlation with the child's motor performance level, indicating that the children with better motor performances used more developmentally advanced patterns in comparison with those with lower scores. However, besides motor maturity, numerous other intrinsic/extrinsic factors may affect the child's performance of this task. The information obtained in this study would assist therapists when working with the children with DD, so that they can provide individualized treatment rather than guiding all such children toward a single, mature pattern. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of astaxanthin on resistance of juvenile prawns Macrobrachium nipponense (Decapoda: Palaemonidae) to physical and chemical stress.

PubMed

Tizkar, Babak; Seidavi, Alireza; Ponce-Palafox, Jesús Trinidad; Pourashoori, Parastoo

2014-12-01

In recent years, the use of new scientific techniques has effectively improved aquaculture production processes. Astaxanthin has various properties in aquaculture and its antioxidant benefits have been closely related to stress resistance; besides, it is an essential factor for growth in many crustaceans and fish. The objective of this study was to evaluate the resistance of prawn (Macrobrachium nipponense) fed diets containing different amounts of astaxanthin (AX) to the shock and stress of different physicochemical environments. A 70-day trial was conducted to evaluate the effect of supplementation of a source of astaxanthin (Carophyll Pink, 10% astaxanthin, w/w, Hoffman-La Roche, Switzerland) at various levels in the diet of M. nipponense juveniles. Four dry diets were prepared: AX0 without astaxanthin, AX50 with 50 mg/kg, AX100 with 100 mg/kg, and AX150 with 150 mg/kg astaxanthin. The feeding trial was conducted in a recirculation water system consisting of 12 fiberglass tanks (1000L) used for holding prawns. Three replicate aquaria were initially stocked with 36 org/m2 per tank. During the trial, prawns were maintained on a 12:12-h light:dark photoperiod with an ordinary incandescent lamp, and the water quality parameters were maintained as follows: water temperature, 25-26°C; salinity, 1 g/L; pH, 8.5-8.8; dissolved oxygen, 6.0-6.5 mg/L; and ammonia-nitrogen, 0.05 mg/L. Incorporation of AX, production output, and physiological condition were recorded after 10 weeks of feeding. At the end of the growing period, the prawns were exposed to thermal shock (0°C), ammonia (0.75 mg/L), and reduced oxygen (0.5 mg/L). The time to lethargy and the time to complete death of the prawns were recorded. The results showed that control prawns had the shortest time to lethargy and death compared with prawns subjected to the other treatments. The results of this study have shown that the amount of muscle tissue and gill carotenoids in prawn fed with an AX150 diet showed greater reduction than those exposed to other treatments. It is possible that higher levels of astaxanthin in the body under oxygen reduction stress can be beneficial for prawns. These results suggest that male prawns showed lethargy earlier than females, and the percentage of carotenoid reduction in muscle and gill tissues was higher in males.

Effect of dose rate on residual γ-H2AX levels and frequency of micronuclei in X-irradiated mouse lymphocytes.

PubMed

Turner, H C; Shuryak, I; Taveras, M; Bertucci, A; Perrier, J R; Chen, C; Elliston, C D; Johnson, G W; Smilenov, L B; Amundson, S A; Brenner, D J

2015-03-01

The biological risks associated with low-dose-rate (LDR) radiation exposures are not yet well defined. To assess the risk related to DNA damage, we compared the yields of two established biodosimetry end points, γ-H2AX and micronuclei (MNi), in peripheral mouse blood lymphocytes after prolonged in vivo exposure to LDR X rays (0.31 cGy/min) vs. acute high-dose-rate (HDR) exposure (1.03 Gy/min). C57BL/6 mice were total-body irradiated with 320 kVP X rays with doses of 0, 1.1, 2.2 and 4.45 Gy. Residual levels of total γ-H2AX fluorescence in lymphocytes isolated 24 h after the start of irradiation were assessed using indirect immunofluorescence methods. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to determine apoptotic cell frequency in lymphocytes sampled at 24 h. Curve fitting analysis suggested that the dose response for γ-H2AX yields after acute exposures could be described by a linear dependence. In contrast, a linear-quadratic dose-response shape was more appropriate for LDR exposure (perhaps reflecting differences in repair time after different LDR doses). Dose-rate sparing effects (P < 0.05) were observed at doses ≤2.2 Gy, such that the acute dose γ-H2AX and TUNEL-positive cell yields were significantly larger than the equivalent LDR yields. At the 4.45 Gy dose there was no difference in γ-H2AX expression between the two dose rates, whereas there was a two- to threefold increase in apoptosis in the LDR samples compared to the equivalent 4.45 Gy acute dose. Micronuclei yields were measured at 24 h and 7 days using the in vitro cytokinesis-blocked micronucleus (CBMN) assay. The results showed that MNi yields increased up to 2.2 Gy with no further increase at 4.45 Gy and with no detectable dose-rate effect across the dose range 24 h or 7 days post exposure. In conclusion, the γ-H2AX biomarker showed higher sensitivity to measure dose-rate effects after low-dose LDR X rays compared to MNi formation; however, confounding factors such as variable repair times post exposure, increased cell killing and cell cycle block likely contributed to the yields of MNi with accumulating doses of ionizing radiation.

Evaluating the genotoxicity of topoisomerase-targeted antibiotics

PubMed Central

Smart, Daniel J.; Lynch, Anthony M.

2012-01-01

Antibiotics like fluoroquinolones (FQs) that target bacterial type II topoisomerases pose a potential genotoxic risk due to interactions with mammalian topoisomerase II (TOPO II) counterparts. Inhibition of TOPO II can lead to the generation of clastogenic DNA double-strand breaks (DSBs) that can in turn manifest in mutagenesis. Thus, methods that allow early identification of drugs that present the greatest hazard are warranted. A rapid, medium-throughput and predictive genotoxicity screen that can be applied to bacterial type II topoisomerase inhibitors is described herein. Maximal induction of the DSB biomarker serine139-phosphorylated histone H2AX (γH2AX) in L5178Y cells was quantified via flow cytometry and correlated with data derived from the mouse lymphoma screen (MLS), a default assay used to rank genotoxic potential. When applied to a class of novel bacterial type II topoisomerase inhibitors (NBTIs) in lead-optimisation, maximal γH2AX induction >1.4-fold (relative to controls) identified 22/27 NBTIs that induced >6-fold relative mutation frequency (MF) in MLS. Moreover, response signatures comprising of γH2AX induction and G2M cell cycle arrest elucidated using this approach suggested that these NBTIs, primarily of the H class, operated via a TOPO II poison-like mechanism of action (MoA) similar to FQs. NBTIs that induced ≤6-fold relative MF, which were mainly A class-derived, had less impact on γH2AX (≤1.4-fold) and also evoked G1 arrest, indicating that their cytotoxic effects were likely mediated through a non-poison MoA. Concordance between assays was 86% (54/63) when 1.4- and 6-fold ‘cut offs’ were applied. These findings were corroborated through inspection of human TOPO IIα IC50 data as NBTIs exhibiting equivalent inhibitory capacities had differing genotoxic potencies. Deployed in an early screening capacity, the γH2AX by flow assay coupled with structure–activity relationship evaluation can provide insight into MoA and impact medicinal chemistry efforts, ultimately leading to the production of inherently safer molecules. PMID:22155972

Clinical characteristics of importance to outcome in patients with axial spondyloarthritis: protocol for a prospective descriptive and exploratory cohort study.

PubMed

Andreasen, Rikke Asmussen; Kristensen, Lars Erik; Ellingsen, Torkell; Christensen, Robin; Baraliakos, Xenofon; Wied, Jimmi; Aalykke, Claus; Ulstrup, Thomas; Schiøttz-Christensen, Berit; Horn, Hans Christian; Emamifar, Amir; Duerlund, Bent; Fischer, Lars; Hansen, Inger Marie Jensen

2017-07-10

Spondyloarthritis (SpA) is a heterogeneous spectrum of rheumatic diseases with either predominantly axial inflammatory symptoms of the spine and sacroiliac joints or predominantly peripheral arthritis. The two main entities of axial SpA (axSpA) are ankylosing spondylitis or non-radiographic axSpA (nr-axSpA). Tumour necrosis factor-α inhibitors have revolutionised the treatment of patients with axSpA who failed to respond to non-steroidal anti-inflammatory drugs and physical therapy. Chronic pain is common in patients with SpA and may still persist despite the lack of signs of inflammation. This has led researchers to hypothesise that central pain sensitisation may play a role in the generation of chronic pain in SpA. The painDETECT Questionnaire (PDQ) is a screening tool developed to detect neuropathic pain components. The primary objective is to explore the prognostic value of the PDQ regarding treatment response in patients with axSpA 3 months after initiating a biological agent. Secondary aim is to evaluate the impact of extra-articular manifestations, comorbidities and patient-reported outcomes and elucidate if these factors influence treatment response. We will include 60 participants (≥18 years of age) diagnosed with axSpA independent of main entity, who initiate or switch treatment of a biologic. Data will be collected at baseline and at endpoint following Danish clinical practice (≥3 months) of treatment with biologics. We will explore whether the PDQ and other phenotypical patient characteristics are prognostically important for response to biological therapy according to established response criteria like 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (50%) and Ankylosing Spondylitis Disease Activity Score. The study is approved by the Region of Southern Denmark's Ethics committee (S-20160094) and has been designed in cooperation with patient representatives. The study is registered at clinicaltrials.gov (NCT02948608, pre-results). Dissemination will occur through publication(s) in international peer-reviewed journal(s). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

γ-H2AX responds to DNA damage induced by long-term exposure to combined low-dose-rate neutron and γ-ray radiation.

PubMed

Zhang, Junlin; He, Ying; Shen, Xianrong; Jiang, Dingwen; Wang, Qingrong; Liu, Qiong; Fang, Wen

2016-01-01

Risk estimates for low-dose radiation (LDR) remain controversial. The possible involvement of DNA repair-related genes in long-term low-dose-rate neutron-gamma radiation exposure is poorly understood. In this study, 60 rats were divided into control groups and irradiated groups, which were exposed to low-dose-rate n-γ combined radiation (LDCR) for 15, 30, or 60 days. The effects of different cumulative radiation doses on peripheral blood cell (PBC), subsets of T cells of peripheral blood lymphocytes (PBL) and DNA damage repair were investigated. Real-time PCR and immunoblot analyses were used to detect expression of DNA DSB-repair-related genes involved in the NHEJ pathway, such as Ku70 and Ku80, in PBL. The mRNA level of H2AX and the expression level of γ-H2AX were detected by real-time PCR, immunoblot, and flow cytometry. White blood cells (WBC) and platelets (PLT) of all ionizing radiation (IR) groups decreased significantly, while no difference was seen between the 30 day and 60 day exposure groups. The numbers of CD3(+), CD4(+) T cells and CD4(+)/CD8(+) in the PBL of IR groups were lower than in the control group. In the 30 day and 60 day exposure groups, CD8(+) T cells decreased significantly. Real-time PCR and immunoblot results showed no significant difference in the mRNA and protein expression of Ku70 and Ku80 between the control groups and IR groups. However, the mRNA of H2AX increased significantly, and there was a positive correlation with dose. There was no difference in the protein expression of γ-H2AX between 30 day and 60 day groups, which may help to explain the damage to PBL. In conclusion, PBL damage increased with cumulative dose, suggesting that γ-H2AX, but neither Ku70 nor Ku80, plays an important role in PBL impairment induced by LDCR. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Laser-Induced Fluorescence and Performance Analysis of the Ultra-Compact Combustor

DTIC Science & Technology

2008-06-01

fiber as a sealant. .............................................................................................. 68  Figure 37. A view of AFIT’s flat...ratio cm Centimeters CO Carbon Monoxide CO2 Carbon Dioxide Cp Constant-pressure specific heat CxHy General formula of a hydrocarbon C2H4...Standard liters per minute T Temperature, thrust U Combustor inlet velocity v Velocity x Number of carbon atoms y Number of hydrogen atoms (A-X) OH

[Efficiency of different celecoxib regimens in patients with active axial spondyloarthritis: Results of the 4-week pilot open-label comparative single-center study 'AIM'].

PubMed

Gaydukova, I Z; Gamayunova, К A; Dorogoykina, K D; Rebrov, A P

To compare the efficiency and safety of two celecoxib regimens in the short-term treatment of patients with axial spondyloarthritis (axSpA). Examinations were made in 40 patients with axSpA (the 2009 ASAS criteria; age, 38.5±12.1 years; 29 (72.5%) men; axSpA duration, 6.67±5.8 years; BASDAI ≥4.0), who were randomly divided into two groups: 1) 20 patients who received celecoxib 400 mg/day for 30 days; 2) 20 patients who took celecoxib 600 mg/day for 7 days, then the drug was continued at a dose of 200 mg/day for 1 month. High-sensitivity C-reactive protein (CRP) was determined; back pain was assessed using a visual analog scale; ASDAS-CRP scores were calculated at baseline (day 0) and on days 8 and 30. On days 0, 8, and 30 of taking celecoxib 400 mg, the back pain scores were 6.0±3.01, 5.06±2.04, and 5.53±2.35; CRP levels, 24.13±21.46; 27.3±29.3%, and 13.1±21.3 mg/l; erythrocyte sedimentation rate (ESR), 15.25±14.36, 11.85±13.6, and 9.5±6.34 mm/h, respectively (p≥0.05 for all differences in all indicators relative to the baseline values). ASDAS was 3.34±1.02 at baseline, 2.74±1.14 on day 8, and 2.18±1.05 on day 30 (p=0.016 and p=0,000 for differences from the baseline values). In the patients using the dose de-escalation of celecoxib, the back pain scores were 4.95±1.6, 4.11±1.0, and 4.89±2.1 at baseline and on days 8 and 30, respectively (p=0.38 and p=0.065 for the differences from the baseline values); the CRP levels were 15.3±12.5, 12.1±10.8, and 7.5±4.5 mg/l, respectively (p=0.3 and p=0.001); ESR, 13.35±7.2, 15.7±11.6, and 15.16±8.9 mm/h (p≥0.05). At baseline and on days 8 and 30, ASDAS was 3.1±0.6, 2.22±0.7, and 3.47±0.56, respectively (p=0.02 and p=0.000). No differences were found in the rate of adverse events. Different regimens using nonsteroidal anti-inflammatory drugs demonstrated their feasibility, efficiency, and safety in AxSpA patients with high disease activity. The continuous use of celecoxib showed a gradual decrease in clinical and laboratory activity. The de-escalation dose of celecoxib achieved a permanent laboratory activity reduction and pain relief when using 600 mg celecoxib, and after reducing its dose to 200 mg/day, there was a decrease in laboratory disease activity without substantially changing the patients' functional activity. The safety of the comparable regimens was comparable.

Detection of DNA Double Strand Breaks by γH2AX Does Not Result in 53bp1 Recruitment in Mouse Retinal Tissues

PubMed Central

Müller, Brigitte; Ellinwood, N. M.; Lorenz, Birgit; Stieger, Knut

2018-01-01

Gene editing is an attractive potential treatment of inherited retinopathies. However, it often relies on endogenous DNA repair. Retinal DNA repair is incompletely characterized in humans and animal models. We investigated recruitment of the double stranded break (DSB) repair complex of γH2AX and 53bp1 in both developing and mature mouse neuroretinas. We evaluated the immunofluorescent retinal expression of these proteins during development (P07-P30) in normal and retinal degeneration models, as well as in potassium bromate induced DSB repair in normal adult (3 months) retinal explants. The two murine retinopathy models used had different mutations in Pde6b: the severe rd1 and the milder rd10 models. Compared to normal adult retina, we found increased numbers of γH2AX positive foci in all retinal neurons of the developing retina in both model and control retinas, as well as in wild type untreated retinal explant cultures. In contrast, the 53bp1 staining of the retina differed both in amount and character between cell types at all ages and in all model systems. There was strong pan nuclear staining in ganglion, amacrine, and horizontal cells, and cone photoreceptors, which was attenuated. Rod photoreceptors did not stain unequivocally. In all samples, 53bp1 stained foci only rarely occurred. Co-localization of 53bp1 and γH2AX staining was a very rare event (< 1% of γH2AX foci in the ONL and < 3% in the INL), suggesting the potential for alternate DSB sensing and repair proteins in the murine retina. At a minimum, murine retinal DSB repair does not appear to follow canonical pathways, and our findings suggests further investigation is warranted. PMID:29765300

Axial spondyloarthritis criteria and modified NY criteria: issues and controversies.

PubMed

Deodhar, Atul

2014-06-01

The Assessment of Spondyloarthritis International Society (ASAS) classification criteria for axial spondyloarthritis (axSpA) developed in 2009 was a major step forward, since the 1984 modified New York (mNY) criteria for classification of ankylosing spondylitis (AS) were too insensitive to identify patients with early signs of axial inflammation. In the absence of "diagnostic" criteria for either axSpA or AS, both of these "classification" criteria are routinely used in clinical practice to diagnose patients. However, there is a real danger of "misdiagnosis" if classification criteria are applied erroneously by ticking "yes" or "no" boxes in an undiagnosed patient. This concern was raised and discussed at the FDA Arthritis Advisory Committee meeting in June 2013, and the committee warned that if TNF inhibitors are approved to treat axSpA, such misdiagnosis could lead to serious consequences. To gauge the SPARTAN members' familiarity with these criteria and these issues surrounding them, as well as to investigate how they are using these criteria in daily practice, two questionnaires (one each for mNY and ASAS axSpA criteria) were sent to the "full" members of SPARTAN before the annual meeting. The results showed that more than 60% of the responders used these criteria most of the time in practice to help them diagnose a patient, and nearly three fourth of responders agreed with the FDA Advisory Committee and would like to see some objective signs before prescribing TNF inhibitors to axSpA patients. A majority of responders looked at the sacroiliac joint x-rays themselves to diagnose sacroiliitis, even though they had difficulty in grading the x-rays. In a live vote at the meeting, 88% of the members suggested that SPARTAN should engage in either modifying the existing criteria or develop new diagnostic criteria for axial spondyloarthritis.

AxBAxB… pulsed atomic layer deposition: Numerical growth model and experiments

NASA Astrophysics Data System (ADS)

Muneshwar, Triratna; Cadien, Ken

2016-02-01

Atomic layer deposition (ALD) is widely used for the fabrication of advanced semiconductor devices and related nanoscale structures. During ALD, large precursor doses (>1000 L per pulse) are often required to achieve surface saturation, of which only a small fraction is utilized in film growth while the rest is pumped from the system. Since the metal precursor constitutes a significant cost of ALD, strategies to enhance precursor utilization are essential for the scaling of ALD processes. In the precursor reaction step, precursor physisorption is restricted by steric hindrance (mA1) from ligands on the precursor molecules. On reaction, some of these ligands are removed as by-products resulting in chemisorbed species with reduced steric hindrance (mA1 → mA2, where mA2 < mA1) and some of the initially hindered surface reaction sites becoming accessible for further precursor physisorption. To utilize these additional reaction sites, we propose a generalized AxBAxB… pulsed deposition where the total precursor dose (ΦA) is introduced as multiple x (x > 1, x ∈ I) short-pulses rather than a single pulse. A numerical first-order surface reaction kinetics growth model is presented and applied to study the effect of AxBAxB… pulsed ALD on the growth per cycle (GPC). The model calculations predict higher GPC for AxBAxB… pulsing than with ABAB… deposition. In agreement with the model predictions, with AxBAxB… pulsed deposition, the GPC was found to increase by ˜46% for ZrN plasma enhanced ALD (PEALD), ˜49% for HfO2 PEALD, and ˜8% for thermal Al2O3 ALD with respect to conventional ABAB… pulsed growth.

The influence of dietary antioxidant on ovarian eggs and levels of vitamin E, C, A, astaxanthin, β-carotene and oxidative stres in tissues of Astacus leptodactylus (Eschscholtz) during reproduction.

PubMed

Barim-Oz, O; Sahin, H

2016-12-30

The experiment was conducted to determine the most effective antioxidant (among the vitamin E (VE), vitamin C (VC), vitamin A (VA), astaxanthine (AX), β-carotene (βC)) on the ovarian egg number and size, level of VE, VC, VA, AX, βC and oxidative stress (as malondialdehyde (MDA)) in the hepatopancreas, ovarian, gills and muscle tissue during ovarian development of Astacus leptodactylus. One control (C) and five experimental diets (EE, EC, EA, EAX and EβC) were prepared. The EE, EC, EA, EAX and EβC groups were formed by added 150 mg kg-1 VE, 200 mg kg-1 VC, 240 mg kg-1 VA, 200 mg kg-1 AX and 200 mg kg-1 βC to diet C, respectively. At the end of the experiment found that the dietary antioxidants increased ovarian egg number and size and reduced the level of MDA in the tissues. Ovarian egg number and size were highest in the EE and EAX diet groups in the comparison to control (p<0.001). The level of MDA in the tissues was lowest in the EAX diet group in the comparison to control (p<0.001). The highest levels of VE, VC, VA, AX and βC were found in the hepatopancreas and ovarian compared with muscle and gills. The highest level of MDA also was determined in the ovarian according to other tissues. In conclusion, the VE and AX in broodstock diets were the most effective antioxidants on the ovarian egg number and size of A. leptodactylus.

Complex engagement of DNA damage response pathways in human cancer and in lung tumor progression.

PubMed

Nuciforo, Paolo Giovanni; Luise, Chiara; Capra, Maria; Pelosi, Giuseppe; d'Adda di Fagagna, Fabrizio

2007-10-01

Tumor initiation and progression provide a multitude of occasions for the generation of DNA damage and the consequent activation of the DNA damage response (DDR) pathway. DDR signaling involves the engagement of key factors such as ATM, CHK2, 53BP1 and the phosphorylation of histone H2AX (gamma-H2AX). The systematic study of DDR in human tumors and normal tissues by high-throughput tissue microarrays revealed that ATM and gamma-H2AX were engaged in cancer but the extent of their activation was strongly affected by the organ and cell type involved, whereas 53BP1 loss was the most consistent feature among the tumor studied. Unexpectedly, we also observed activated DDR markers in morphologically normal tissues, also in association with inflammation. Analysis of the dynamic engagement of DDR along the different stages of lung tumorigenesis showed that 53BP1 loss occurs early at the transition from normal to dysplastic change whereas the activated forms of ATM and CHK2, but not gamma-H2AX, initially accumulate in pre-invasive lesions and are then lost during tumor progression. In individual lung tumors, the activation of ATM, CHK2 and the presence of 53BP1 were consistently correlated, whereas gamma-H2AX did not correlate with activated ATM. Finally, the study of associations between critical clinicopathological parameters and activated DDR factors highlighted a statistically meaningful correlation between reduced local tumor extension and the phosphorylation of ATM, CHK2 and the presence of 53BP1, whereas no significant correlations with parameters such as survival or relapse of early-stage lung carcinomas were found.

DNA double-strand break repair of blood lymphocytes and normal tissues analysed in a preclinical mouse model: implications for radiosensitivity testing.

PubMed

Rübe, Claudia E; Grudzenski, Saskia; Kühne, Martin; Dong, Xiaorong; Rief, Nicole; Löbrich, Markus; Rübe, Christian

2008-10-15

Radiotherapy is an effective cancer treatment, but a few patients suffer severe radiation toxicities in neighboring normal tissues. There is increasing evidence that the variable susceptibility to radiation toxicities is caused by the individual genetic predisposition, by subtle mutations, or polymorphisms in genes involved in cellular responses to ionizing radiation. Double-strand breaks (DSB) are the most deleterious form of radiation-induced DNA damage, and DSB repair deficiencies lead to pronounced radiosensitivity. Using a preclinical mouse model, the highly sensitive gammaH2AX-foci approach was tested to verify even subtle, genetically determined DSB repair deficiencies known to be associated with increased normal tissue radiosensitivity. By enumerating gammaH2AX-foci in blood lymphocytes and normal tissues (brain, lung, heart, and intestine), the induction and repair of DSBs after irradiation with therapeutic doses (0.1-2 Gy) was investigated in repair-proficient and repair-deficient mouse strains in vivo and blood samples irradiated ex vivo. gammaH2AX-foci analysis allowed to verify the different DSB repair deficiencies; even slight impairments caused by single polymorphisms were detected similarly in both blood lymphocytes and solid tissues, indicating that DSB repair measured in lymphocytes is valid for different and complex organs. Moreover, gammaH2AX-foci analysis of blood samples irradiated ex vivo was found to reflect repair kinetics measured in vivo and, thus, give reliable information about the individual DSB repair capacity. gammaH2AX analysis of blood and tissue samples allows to detect even minor genetically defined DSB repair deficiencies, affecting normal tissue radiosensitivity. Future studies will have to evaluate the clinical potential to identify patients more susceptible to radiation toxicities before radiotherapy.

Implant material and design alter construct stiffness in distal femur locking plate fixation: a pilot study.

PubMed

Schmidt, Ulf; Penzkofer, Rainer; Bachmaier, Samuel; Augat, Peter

2013-09-01

Construct stiffness affects healing of bones fixed with locking plates. However, variable construct stiffness reported in the literature may be attributable to differing test configurations and direct comparisons may clarify these differences. We therefore asked whether different distal femur locking plate systems and constructs will lead to different (1) axial and rotational stiffness and (2) fatigue under cyclic loading. We investigated four plate systems for distal femur fixation (AxSOS, LCP, PERI-LOC, POLYAX) of differing designs and materials using bone substitutes in a distal femur fracture model (OTA/AO 33-A3). We created six constructs of each of the four plating systems. Stiffness under static and cyclic loading and fatigue under cyclic loading were measured. Mean construct stiffness under axial loading was highest for AxSOS (100.8 N/mm) followed by PERI-LOC (80.8 N/mm) and LCP (62.6 N/mm). POLYAX construct stiffness testing showed the lowest stiffness (51.7 N/mm) with 50% stiffness of AxSOS construct testing. Mean construct stiffness under torsional loading was similar in the group of AxSOS and PERI-LOC (3.40 Nm/degree versus 3.15 Nm/degree) and in the group of LCP and POLYAX (2.63 Nm/degree versus 2.56 Nm/degree). The fourth load level of > 75,000 cycles was reached by three of six AxSOS, three of six POLYAX, and two of six PERI-LOC constructs. All others including all LCP constructs failed earlier. Implant design and material of new-generation distal femur locking plate systems leads to a wide range of differences in construct stiffness. Assuming construct stiffness affects fracture healing, these data may influence surgical decision-making in choosing an implant system.

Theoretical investigation on radiation tolerance of {{\\boldsymbol{M}}}_{{\\boldsymbol{n}}+1}{{\\boldsymbol{AX}}}_{{\\boldsymbol{n}}} phases

NASA Astrophysics Data System (ADS)

Yin, Ke-Di; Zhang, Xi-Tong; Huang, Qing; Xue, Jian-Ming

2017-06-01

Ternary {M}n+1{{AX}}n phases with layered hexagonal structures, as candidate materials used for next-generation nuclear reactors, have shown great potential in tolerating radiation damage due to their unique combination of ceramic and metallic properties. However, {M}n+1{{AX}}n materials behave differently in amorphization when exposed to energetic neutron and ion irradiations in experiment. We first analyze the irradiation tolerances of different {M}n+1{{AX}}n (MAX) phases in terms of electronic structure, including the density of states (DOS) and charge density map. Then a new method based on the Bader analysis with the first-principle calculation is used to estimate the stabilities of MAX phases under irradiation. Our calculations show that the substitution of Cr/V/Ta/Nb by Ti and Si/Ge/Ga by Al can increase the ionicities of the bonds, thus strengthening the radiation tolerance. It is also shown that there is no obvious difference in radiation tolerance between {M}n+1A{{{C}}}n and {M}n+1A{{{N}}}n due to the similar charge transfer values of C and N atoms. In addition, the improved radiation tolerance from Ti3AlC2 to Ti2AlC (Ti3AlC2 and Ti2AlC have the same chemical elements), can be understood in terms of the increased Al/TiC layer ratio. Criteria based on the quantified charge transfer can be further used to explore other {M}n+1{{AX}}n phases with respect to their radiation tolerance, playing a critical role in choosing appropriate MAX phases before they are subjected to irradiation in experimental test for future nuclear reactors. Project supported by the National Natural Science Foundation of China (Grant Nos. 91226202 and 91426304).

Extraction of soluble arabinoxylan from enzymatically pretreated wheat bran and production of short xylo-oligosaccharides and arabinoxylo-oligosaccharides from arabinoxylan by glycoside hydrolase family 10 and 11 endoxylanases.

PubMed

Mathew, Sindhu; Karlsson, Eva Nordberg; Adlercreutz, Patrick

2017-10-20

The enzymatic, ecofriendly pretreatment of wheat bran with α-amylase from Bacillus amyloliquifaciens or B. licheniformis at 90°C for 1.5h followed by Neutrase at 50°C for 4h, aqueous liquefaction at 121°C for 15h and ethanol precipitation enabled the production of soluble arabinoxylan (AX) with purity of 70.9% and 68.4% (w/w) respectively. Process alternatives tried, to simplify the process and curtail the cost resulted in AX products with different purities, yields and arabinose to xylose ratio (A/X). Among the two glycoside hydrolase (GH) family endoxylanases evaluated, GH10 family hydrolysed soluble AX more efficiently with xylanase from Geobacillus stearothermophilus T-6 (GsXyn10A) producing maximum amount of quantifiable short xylo-oligosaccharides (XOS) and arabinoxylo-oligosaccharides (AXOS) (53% w/w) followed by the catalytic module of Rhodothermus marinus Xyn10A (RmXyn10A-CM) with 37% (w/w) conversion. The GH11 family endoxylanases, from Thermomyces lanuginosus (Pentopan Mono BG™) and Neocallimastix patriciarum (NpXyn11A) gave conversions of 21% and 22% (w/w) of the soluble AX, respectively (major AXOS products were not quantified). In addition to the XOS formed such as X 2 , X 3 and X 4 , the AXOS products identified were A 3 X and A 2 XX in the case of GsXyn10A and RmXyn10A-CM while Pentopan Mono BG and NpXyn11A produced XA 3 XX as the major AXOS product. Copyright © 2017 Elsevier B.V. All rights reserved.

AxTract: Toward microstructure informed tractography.

PubMed

Girard, Gabriel; Daducci, Alessandro; Petit, Laurent; Thiran, Jean-Philippe; Whittingstall, Kevin; Deriche, Rachid; Wassermann, Demian; Descoteaux, Maxime

2017-11-01

Diffusion-weighted (DW) magnetic resonance imaging (MRI) tractography has become the tool of choice to probe the human brain's white matter in vivo. However, tractography algorithms produce a large number of erroneous streamlines (false positives), largely due to complex ambiguous tissue configurations. Moreover, the relationship between the resulting streamlines and the underlying white matter microstructure characteristics remains poorly understood. In this work, we introduce a new approach to simultaneously reconstruct white matter fascicles and characterize the apparent distribution of axon diameters within fascicles. To achieve this, our method, AxTract, takes full advantage of the recent development DW-MRI microstructure acquisition, modeling, and reconstruction techniques. This enables AxTract to separate parallel fascicles with different microstructure characteristics, hence reducing ambiguities in areas of complex tissue configuration. We report a decrease in the incidence of erroneous streamlines compared to the conventional deterministic tractography algorithms on simulated data. We also report an average increase in streamline density over 15 known fascicles of the 34 healthy subjects. Our results suggest that microstructure information improves tractography in crossing areas of the white matter. Moreover, AxTract provides additional microstructure information along the fascicle that can be studied alongside other streamline-based indices. Overall, AxTract provides the means to distinguish and follow white matter fascicles using their microstructure characteristics, bringing new insights into the white matter organization. This is a step forward in microstructure informed tractography, paving the way to a new generation of algorithms able to deal with intricate configurations of white matter fibers and providing quantitative brain connectivity analysis. Hum Brain Mapp 38:5485-5500, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Periodic trends in bond dissociation energies. A theoretical study.

PubMed

Mó, Otilia; Yáñez, Manuel; Eckert-Maksić, Mirjana; Maksić, Zvonimir B; Alkorta, Ibón; Elguero, José

2005-05-19

Bond dissociation energies (BDEs) of all possible A-X single bonds involving the first- and second-row atoms, from Li to Cl, where the free valences are saturated by hydrogens, have been estimated through the use of the G3-theory and at the B3LYP/6-311+G(3df,2pd)//B3LYP/6-31G(2df,p) DFT level of theory. BDEs exhibit a periodical behavior. The A-X (A = Li, Be, B, Na, Mg, Al, and Si) BDEs show a steady increase along the first and the second row of the periodic table as a function of the atomic number Z(X). For A-X bonds involving electronegative atoms (A = C, N, O, F, P, S, and Cl) the bond energies achieve a maximum around Z(X) = 5. The same behavior is observed when BDEs are plotted against the electronegativity chi(X) of the atom X. Thus, for A-X bonds (A = Li, Be, B, Na, Mg, Al, Si), the BDEs for a fixed A increases, grosso modo, as the electronegativity differences between X and A increase, with some exceptions, which reflect the differences in the relaxation energies of the radicals produced upon the bond cleavage. A similar trend, albeit less pronounced, is found for single A-X bonds, where A = C, N, O, F, P, S, and Cl. However, there is an additional feature embodied in the enhancement of the strength of the A-boron bonds due to the ability of boron to act as a strong electron acceptor. The trends in bond lengths and charge densities at the bond critical points are in line with the aforementioned behavior.

Work disability in non-radiographic axial spondyloarthritis patients before and after start of anti-TNF therapy: a population-based regional cohort study from southern Sweden.

PubMed

Wallman, Johan K; Jöud, Anna; Olofsson, Tor; Jacobsson, Lennart T H; Bliddal, Henning; Kristensen, Lars E

2017-05-01

The aim was to assess work-loss days before and after commencement of anti-TNF treatment in patients with non-radiographic axial spondylarthritis (nr-axSpA). Bionaïve nr-axSpA patients (n = 75), aged 17-62 years, fulfilling the Assessment of SpondyloArthritis international Society criteria for axial spondyloarthritis and starting anti-TNF treatment during 2004-11, were retrieved from the observational South Swedish Arthritis Treatment Group study. Patient information was linked to Swedish Social Insurance Agency data on sick leave and disability pension from 1 year before to 2 years after anti-TNF initiation. Matched population references were included for comparison and to adjust for secular trends. The nr-axSpA patients had a median age of 35 years and disease duration of 6 years at the start of treatment. During the 2 years after anti-TNF initiation, mean work-loss days (including both sick leave and disability pension) in the nr-axSpA group decreased significantly from 3.4 to 1.9 times more than among the population references. The effect was seen on sick leave, whereas disability pension levels remained similar in both groups throughout. Anti-TNF therapy in nr-axSpA was associated with a significant and sustained improvement of work disability over 2 years. However, the proportion of work-loss days remained almost twice as high as in the general population at the end of follow-up. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

VizieR Online Data Catalog: u'BVg'r'i'z' light curves of SN 2008ax (Pastorello+, 2008)

NASA Astrophysics Data System (ADS)

Pastorello, A.; Kasliwal, M. M.; Crockett, R. M.; Valenti, S.; Arbour, R.; Itagaki, K.; Kaspi, S.; Gal-Yam, A.; Smartt, S. J.; Griffith, R.; Maguire, K.; Ofek, E. O.; Seymour, N.; Stern, D.; Wiethoff, W.

2010-02-01

SN 2008ax is one of the best ever monitored core-collapse SNe, starting with a deep pre-explosion image obtained only 6h prior to the SN discovery of Mostardi et al. (2008CBET.1280....1M). The observational campaign of SN 2008ax started soon after the discovery and covered a period of about 70d. Photometry has been obtained at the 2-m Liverpool Telescope in La Palma (Canary Islands, Spain) and the 60-inch Telescope of the Palomar Observatory. In addition, unfiltered data collected by amateur astronomers have been used in our analysis. These data have been scaled to the Johnson-Bessell V-band or the Sloan r'-band photometry, depending on the sensitivity curves of the CCDs used in these observations. (2 data files).

Microwaves from GSM mobile telephones affect 53BP1 and gamma-H2AX foci in human lymphocytes from hypersensitive and healthy persons.

PubMed

Markovà, Eva; Hillert, Lena; Malmgren, Lars; Persson, Bertil R R; Belyaev, Igor Y

2005-09-01

The data on biologic effects of nonthermal microwaves (MWs) from mobile telephones are diverse, and these effects are presently ignored by safety standards of the International Commission for Non-Ionizing Radiation Protection (ICNIRP). In the present study, we investigated effects of MWs of Global System for Mobile Communication (GSM) at different carrier frequencies on human lymphocytes from healthy persons and from persons reporting hypersensitivity to electromagnetic fields (EMFs). We measured the changes in chromatin conformation, which are indicative of stress response and genotoxic effects, by the method of anomalous viscosity time dependence, and we analyzed tumor suppressor p53-binding protein 1 (53BP1) and phosphorylated histone H2AX (gamma-H2AX), which have been shown to colocalize in distinct foci with DNA double-strand breaks (DSBs), using immunofluorescence confocal laser microscopy. We found that MWs from GSM mobile telephones affect chromatin conformation and 53BP1/gamma-H2AX foci similar to heat shock. For the first time, we report here that effects of MWs from mobile telephones on human lymphocytes are dependent on carrier frequency. On average, the same response was observed in lymphocytes from hypersensitive and healthy subjects.

The clinical spectrum of late-onset Alexander disease: a systematic literature review.

PubMed

Balbi, Pietro; Salvini, Silvana; Fundarò, Cira; Frazzitta, Giuseppe; Maestri, Roberto; Mosah, Dibo; Uggetti, Carla; Sechi, GianPietro

2010-12-01

Following the discovery of glial fibrillary acidic protein (GFAP) mutations as the causative factor of Alexander disease (AxD), new case reports have recently increased, prompting a more detailed comprehension of the clinical features of the three disease subtypes (infantile, juvenile and adult). While the clinical pattern of the infantile form has been substantially confirmed, the late-onset subtypes (i.e., juvenile and adult), once considered rare manifestations of AxD, have displayed a wider clinical spectrum. Our aim was to evaluate the clinical phenotype of the adult and juvenile forms by reviewing the previously reported cases. Data were collected from previously published reports on 112 subjects affected by neuropathologically or genetically proven adult and juvenile Alexander disease. Although the late-onset forms of AxD show a wide clinical variability, a common pattern emerges from comparing previously reported cases, characterized by pseudo-bulbar signs, ataxia, and spasticity, associated with atrophy of the medulla and upper cervical cord on neuroimaging. Late-onset AxD cases can no longer be considered as rare manifestations of the disease. The clinical pattern usually reflects the topographic localization of the lesions, with adult cases displaying a predominant infratentorial localization of the lesions. Juvenile cases show clinical and radiological features which are intermediate between adult and infantile forms.

Microwaves from GSM Mobile Telephones Affect 53BP1 and γ-H2AX Foci in Human Lymphocytes from Hypersensitive and Healthy Persons

PubMed Central

Markovà, Eva; Hillert, Lena; Malmgren, Lars; Persson, Bertil R. R.; Belyaev, Igor Y.

2005-01-01

The data on biologic effects of nonthermal microwaves (MWs) from mobile telephones are diverse, and these effects are presently ignored by safety standards of the International Commission for Non-Ionizing Radiation Protection (ICNIRP). In the present study, we investigated effects of MWs of Global System for Mobile Communication (GSM) at different carrier frequencies on human lymphocytes from healthy persons and from persons reporting hypersensitivity to electromagnetic fields (EMFs). We measured the changes in chromatin conformation, which are indicative of stress response and genotoxic effects, by the method of anomalous viscosity time dependence, and we analyzed tumor suppressor p53-binding protein 1 (53BP1) and phosphorylated histone H2AX (γ-H2AX), which have been shown to colocalize in distinct foci with DNA double-strand breaks (DSBs), using immunofluorescence confocal laser microscopy. We found that MWs from GSM mobile telephones affect chromatin conformation and 53BP1/γ-H2AX foci similar to heat shock. For the first time, we report here that effects of MWs from mobile telephones on human lymphocytes are dependent on carrier frequency. On average, the same response was observed in lymphocytes from hypersensitive and healthy subjects. PMID:16140623

Nucleotide excision repair-dependent DNA double-strand break formation and ATM signaling activation in mammalian quiescent cells.

PubMed

Wakasugi, Mitsuo; Sasaki, Takuma; Matsumoto, Megumi; Nagaoka, Miyuki; Inoue, Keiko; Inobe, Manabu; Horibata, Katsuyoshi; Tanaka, Kiyoji; Matsunaga, Tsukasa

2014-10-10

Histone H2A variant H2AX is phosphorylated at Ser(139) in response to DNA double-strand break (DSB) and single-stranded DNA (ssDNA) formation. UV light dominantly induces pyrimidine photodimers, which are removed from the mammalian genome by nucleotide excision repair (NER). We previously reported that in quiescent G0 phase cells, UV induces ATR-mediated H2AX phosphorylation plausibly caused by persistent ssDNA gap intermediates during NER. In this study, we have found that DSB is also generated following UV irradiation in an NER-dependent manner and contributes to an earlier fraction of UV-induced H2AX phosphorylation. The NER-dependent DSB formation activates ATM kinase and triggers the accumulation of its downstream factors, MRE11, NBS1, and MDC1, at UV-damaged sites. Importantly, ATM-deficient cells exhibited enhanced UV sensitivity under quiescent conditions compared with asynchronously growing conditions. Finally, we show that the NER-dependent H2AX phosphorylation is also observed in murine peripheral T lymphocytes, typical nonproliferating quiescent cells in vivo. These results suggest that in vivo quiescent cells may suffer from NER-mediated secondary DNA damage including ssDNA and DSB. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of Sn addition on the microstructure and tensile properties of AX55 alloys

NASA Astrophysics Data System (ADS)

Qiu, K. Q.; Huang, P.

2018-04-01

The microstructures and tensile properties at both room and elevated temperatures for both the as-cast and as-aged Mg-5Al-5Ca (AX55) alloy with 0–2 wt% Sn addition were studied. The results indicate that the α-Mg dendrite is gradually refined and the interdendritic Al2Ca and Mg2Ca intermetallics become more connected with Sn addition. The as-cast AX55-1Sn alloy shows optimal ultimate tensile strength (UTS) at testing temperature from 25 to 225 °C. After T61 and T62 heat treatment, the eutectic-lamellar microstructure of the as-cast alloys tends to be spheroidized and distributed uniformly along the grain boundaries. While the alloys with higher Sn content show higher density of granulated and needle-shaped Al2Ca phases precipitated into α-Mg matrix, which results in the increase of UTS, yield strength (YS), elongation and microhardness with Sn addition. The morphology of CaMgSn phase can be improved by T62 treatment, which makes as-aged AX55-2.0Sn alloy exhibit a smaller decrease rate of the UTS at temperature up to 225 °C. The heat resistance of different heat-resistant magnesium alloys were compared and discussed by using the decrease rate of the UTS.

Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration.

PubMed

Vaur, Pauline; Brugg, Bernard; Mericskay, Mathias; Li, Zhenlin; Schmidt, Mark S; Vivien, Denis; Orset, Cyrille; Jacotot, Etienne; Brenner, Charles; Duplus, Eric

2017-12-01

NAD + depletion is a common phenomenon in neurodegenerative pathologies. Excitotoxicity occurs in multiple neurologic disorders and NAD + was shown to prevent neuronal degeneration in this process through mechanisms that remained to be determined. The activity of nicotinamide riboside (NR) in neuroprotective models and the recent description of extracellular conversion of NAD + to NR prompted us to probe the effects of NAD + and NR in protection against excitotoxicity. Here, we show that intracortical administration of NR but not NAD + reduces brain damage induced by NMDA injection. Using cortical neurons, we found that provision of extracellular NR delays NMDA-induced axonal degeneration (AxD) much more strongly than extracellular NAD + Moreover, the stronger effect of NR compared to NAD + depends of axonal stress since in AxD induced by pharmacological inhibition of nicotinamide salvage, both NAD + and NR prevent neuronal death and AxD in a manner that depends on internalization of NR. Taken together, our findings demonstrate that NR is a better neuroprotective agent than NAD + in excitotoxicity-induced AxD and that axonal protection involves defending intracellular NAD + homeostasis.-Vaur, P., Brugg, B., Mericskay, M., Li, Z., Schmidt, M. S., Vivien, D., Orset, C., Jacotot, E., Brenner, C., Duplus, E. Nicotinamide riboside, a form of vitamin B 3 , protects against excitotoxicity-induced axonal degeneration. © FASEB.

[Comparative study on the strength of different mechanisms of operation of multidirectionally angle-stable distal radius plates].

PubMed

Rausch, S; Hoffmeier, K; Gueorguiev, B G; Klos, K; Gras, F; Hofmann, G O; Mückley, T

2011-12-01

Polyaxial angle-stable plating is thought to be particularly beneficial in the management of complex intra-articular fractures of the distal radius. The present study was performed to investigate the strength of polyaxial locking interfaces of distal radius plates. We tested the polyaxial interfaces of 3 different distal radius plates (2.4 mm Variable Angle LCP Two-Column Volar Distal Radius Plate, Synthes, Palmar Classic, Königsee Implantate and VariAx Plate Stryker). The strength of 0° and 10° screw locking angle was obtained during static loading. The strength of Palmar Classic with a 0° locking angle is significantly the best of all tested systems. With a 10° locking angle there is no significant difference between Palmar Classic, Two column Plate and VariAx Plate. The strength of polyaxial interfaces differs between the tested systems. A reduction of ultimate strength is due to increases of screw locking angle. The design of polyaxial locking interfaces should be investigated in human bone models. © Georg Thieme Verlag KG Stuttgart · New York.

Fluoride and calcium-phosphate coated sponges of the magnesium alloy AX30 as bone grafts: a comparative study in rabbits.

PubMed

Lalk, Mareike; Reifenrath, Janin; Angrisani, Nina; Bondarenko, Alexandr; Seitz, Jan-Marten; Mueller, Peter P; Meyer-Lindenberg, Andrea

2013-02-01

Biocompatibility and degradation of magnesium sponges (alloy AX30) with a fluoride (MgF(2) sponge, n = 24, porosity 63 ± 6 %, pore size 394 ± 26 μm) and with a fluoride and additional calcium-phosphate coating (CaP sponge, n = 24, porosity 6 ± 4 %, pore size 109 ± 37 μm) were evaluated over 6, 12 and 24 weeks in rabbit femurs. Empty drill holes (n = 12) served as controls. Clinical and radiological examinations, in vivo and ex vivo μ-computed tomographies and histological examinations were performed. Clinically both sponge types were tolerated well. Radiographs and XtremeCT evaluations showed bone changes comparable to controls and mild gas formation. The μCT80 depicted a higher and more inhomogeneous degradation of the CaP sponges. Histomorphometrically, the MgF(2) sponges resulted in the highest bone and osteoid fractions and were integrated superiorly into the bone. Histologically, the CaP sponges showed more inflammation and lower vascularization. MgF(2) sponges turned out to be better biocompatible and promising, biodegradable bone replacements.

The effect of low versus high approach-motivated positive affect on the balance between maintenance and flexibility.

PubMed

Liu, Liting; Xu, Baihua

2016-05-27

Successful goal-directed behavior in a constantly changing environment requires a balance between maintenance and flexibility. Although some studies have found that positive affect influences this balance differently than neutral affect, one recent study found that motivational intensity of positive affective states influences this balance in a cognitive set-shifting paradigm. However, working memory updating and set shifting are interrelated but distinct components of cognitive control. The present study examined the effect of low versus high approach-motivated positive affect on the balance between maintenance and flexibility in working memory. A simple cuing paradigm (the AX Continuous Performance Task) was employed, and neutral affect and high and low approach-motivated positive affect were induced using affective pictures. The results revealed that, relative to neutral affect, low approach-motivated positive affect attenuated maintenance and increased flexibility, whereas high approach-motivated positive affect promoted maintenance and decreased flexibility. These findings offer further evidence that the effects of positive affect on cognitive control are modulated by approach motivational intensity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Synthetic Infrared Scene: Improving the KARMA IRSG Module and Signature Modelling Tool SMAT

DTIC Science & Technology

2011-03-01

d’engagements impliquant des autodirecteurs infrarouges dans l’environnement de simulation KARMA. Le travail a été réalisé à partir de novembre 2008...infrarouges dans l’environnement de simulation KARMA. Le travail a été réalisé à partir de novembre 2008 jusqu’à mars 2011. Ce rapport de contrat est axé...74 13 Evaluating Performance Validator tool

Determination of Static and Dynamic Stability Derivatives Using Beggar

DTIC Science & Technology

2008-03-01

applies a symmetric Gauss - Seidel method , which solves the generic equation [A]x = b for x by dividing [A] into [A] = ([D][L])[U ] (2.68) 37 where D is...oscillations. Convergence studies on each of these parameters were performed to ensure both convergence and solution independence. Roll stability derivatives...aerodynamic stability parame- ters made dynamic solutions more difficult to compute and less reliable, but modern methods and resources are making this process

Evaluation of Aution Max AX-4030 and 9UB Uriflet, 10PA Aution Sticks urine dipsticks in the automated urine test strip analysis.

PubMed

Rota, Cristina; Biondi, Marco; Trenti, Tommaso

2011-09-26

Aution Max AX-4030, a test strip analyzer recently introduced to the market, represents an upgrade of the Aution Max AX-4280 widely employed for urinalysis. This new instrument model can allocate two different test strips at the same time. In the present study the two instruments have been compared together with the usage of Uriflet 9UB and the recently produced Aution Sticks 10PA urine strips, the latter presenting an additional test area for the measurement of urinary creatinine. Imprecision and correlation between instruments and strips have been evaluated for chemical-physical parameters. Accuracy was evaluated for protein, glucose and creatinine by comparing the semi-quantitative results to those obtained by quantitative methods. The well-known interference effect of high ascorbic acid levels on urine glucose test strip determination was evaluated, ascorbic acid influence was also evaluated on protein and creatinine determination. The two instruments have demonstrated comparable performances: precision and correlation between instruments and strips, evaluated for chemical-physical parameters, were always good. Furthermore, accuracy was always very good: results of protein and glucose semi-quantitative measurements resulted to be highly correlated with those obtained by quantitative methods. Moreover, the semi-quantitative measurements of creatinine, employing Aution Sticks 10PA urine strips, were highly comparable with quantitative results. 10PA urine strips are eligible for urine creatinine determination with the possibility of correcting urinalysis results for urinary creatinine concentration, whenever necessary and calculating the protein creatinine ratio. Further studies should be carried out to evaluate effectiveness and appropriateness of the usage of creatinine semi-quantitative analysis.

Chromosomal rearrangements in uveal melanoma: Chromothripsis.

PubMed

van Poppelen, Natasha M; Yavuzyigitoglu, Serdar; Smit, Kyra N; Vaarwater, Jolanda; Eussen, Bert; Brands, Tom; Paridaens, Dion; Kiliç, Emine; de Klein, Annelies

2018-05-04

Uveal melanoma (UM) is the most common primary intraocular malignancy in the Western world. Recurrent mutations in GNAQ, GNA11, CYSLTR2, PLCB4, BAP1, EIF1AX and SF3B1 are described as well as non-random chromosomal aberrations. Chromothripsis is a rare event in which chromosomes are shattered and rearranged and has been reported in a variety of cancers including UM. SNP arrays of 249 UM from patients who underwent enucleation, biopsy or endoresection were reviewed for the presence of chromothripsis. Chromothripsis was defined as ten or more breakpoints per chromosome involved. Genetic analysis of GNAQ, GNA11, BAP1, SF3B1 and EIF1AX was conducted using Sanger and next-generation sequencing. In addition, immunohistochemistry for BAP1 was performed. Chromothripsis was detected in seven out of 249 tumors and the affected chromosomes were chromosomes 3, 5, 6, 8, 12 and 13. The mean total of fragments per chromosome was 39.8 (range 12 - 116). In one UM, chromothripsis was present in two different chromosomes. GNAQ, GNA11 or CYSLTR2 mutations were present in six of these tumors and five tumors harbored a BAP1 mutation and/or lacked BAP1 protein expression by immunohistochemistry. Four of these tumors metastasized and for the fifth only short follow-up data are available. One of these metastatic tumors tumor harbored an SF3B1 mutation. No EIF1AX mutations were detected in any of the tumors. To conclude, chromothripsis is a rare event in UM, occurring in 2.8% of samples and without significant association with mutations in any of the common UM driver genes. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

A Finite Element Model of a White-Metzner Viscoelastic Polymer Extrudate.

DTIC Science & Technology

1981-02-01

for Va as: Forward Difference: ail~ a WiX + Yl Jjxf + 2 1 jijX 2 + 1 32a~i jAy2 + 0i,j+l = i~j + Da~Ax 1 92a iA*2+ 1 32a *2 ’T -a .Ax + 75. h...and gyro element coincide, and 5. The rotor bearing structure is rigid. For a platform stabilized single degree of freedom gyro, these assumptions lead

High Annular Resolution Stellar Interferometry.

DTIC Science & Technology

1985-07-31

correlation is separable, C3 (Ax,At) = C1 (Ax) C2 (At), then the spatial structure and time evolution are uncorrelated and under these conditions one would...the following one. Reference 6 points out the bias obtained on the shape of the normalised spatial correlation function of dynamic speckle under the...MS student) 1982 H Daum (U1 assistant) 1981 C S ________ 20. 6. MUPID This appendix oontains oopies of the 20 publioations produced under this

Immunomodulatory activity of purified arabinoxylans from finger millet (Eleusine coracana, v. Indaf 15) bran.

PubMed

Savitha Prashanth, M R; Shruthi, R R; Muralikrishna, G

2015-09-01

Biological activities of alkali extracted (Barium hydroxide: BE-480 kDa, Potassium hydroxide: KE1-1080 and KE2-40 kDa), purified arabinoxylans (AX) from the finger millet bran varying in their molecular weight, phenolic acid content, arabinose to xylose ratios were evaluated for their immune-stimulatory activities using murine lymphocytes and peritoneal exudate macrophages. All three purified AX displayed significant (p < 0.001) mitogenic activity and activation of macrophages including phagocytosis. Among these BE has shown higher enhancing lymphocyte proliferation (>2 fold) and macrophage phagocytosis than KE1 and KE2. The above results clearly documented that the immunostimulatory activity of arabinoxylans is directly proportional to the amount of ferulic acid content (0.11 mg/100 g), whereas molecular weight as well as arabinose/xylose ratio, did not have any bearing. Purified AX from the finger millet bran can be explored as a potent natural immunomodulator.

A New Supernova Remnant Coincident with the Slow X-Ray Pulsar AX J1845-0258.

PubMed

Gaensler; Gotthelf; Vasisht

1999-11-20

We report on Very Large Array observations in the direction of the recently discovered slow X-ray pulsar AX J1845-0258. In the resulting images, we find a 5&arcmin; shell of radio emission; the shell is linearly polarized with a nonthermal spectral index. We classify this source as a previously unidentified, young (<8000 yr) supernova remnant (SNR), G29.6+0.1, which we propose is physically associated with AX J1845-0258. The young age of G29.6+0.1 is then consistent with the interpretation that anomalous X-ray pulsars (AXPs) are isolated, highly magnetized neutron stars ("magnetars"). Three of the six known AXPs can now be associated with SNRs; we conclude that AXPs are young ( less, similar10,000 yr) objects and that they are produced in at least 5% of core-collapse supernovae.

γ-H2AX as a biomarker for DNA double-strand breaks in ecotoxicology.

PubMed

Gerić, Marko; Gajski, Goran; Garaj-Vrhovac, Vera

2014-07-01

The visualisation of DNA damage response proteins enables the indirect measurement of DNA damage. Soon after the occurrence of a DNA double-strand break (DSB), the formation of γ-H2AX histone variants is to be expected. This review is focused on the potential use of the γ-H2AX foci assay in assessing the genotoxicity of environmental contaminants including cytostatic pharmaceuticals, since standard methods may not be sensitive enough to detect the damaging effect of low environmental concentrations of such drugs. These compounds are constantly released into the environment, potentially representing a threat to water quality, aquatic organisms, and, ultimately, human health. Our review of the literature revealed that this method could be used in the biomonitoring and risk assessment of aquatic systems affected by wastewater from the production, usage, and disposal of cytostatic pharmaceuticals. Copyright © 2014 Elsevier Inc. All rights reserved.

Dissociable influences of reward motivation and positive emotion on cognitive control.

PubMed

Chiew, Kimberly S; Braver, Todd S

2014-06-01

It is becoming increasingly appreciated that affective and/or motivational influences contribute strongly to goal-oriented cognition and behavior. An unresolved question is whether emotional manipulations (i.e., direct induction of affectively valenced subjective experience) and motivational manipulations (e.g., delivery of performance-contingent rewards and punishments) have similar or distinct effects on cognitive control. Prior work has suggested that reward motivation can reliably enhance a proactive mode of cognitive control, whereas other evidence is suggestive that positive emotion improves cognitive flexibility, but reduces proactive control. However, a limitation of the prior research is that reward motivation and positive emotion have largely been studied independently. Here, we directly compared the effects of positive emotion and reward motivation on cognitive control with a tightly matched, within-subjects design, using the AX-continuous performance task paradigm, which allows for relative measurement of proactive versus reactive cognitive control. High-resolution pupillometry was employed as a secondary measure of cognitive dynamics during task performance. Robust increases in behavioral and pupillometric indices of proactive control were observed with reward motivation. The effects of positive emotion were much weaker, but if anything, also reflected enhancement of proactive control, a pattern that diverges from some prior findings. These results indicate that reward motivation has robust influences on cognitive control, while also highlighting the complexity and heterogeneity of positive-emotion effects. The findings are discussed in terms of potential neurobiological mechanisms.

miR-24-2 controls H2AFX expression regardless of gene copy number alteration and induces apoptosis by targeting antiapoptotic gene BCL-2: a potential for therapeutic intervention.

PubMed

Srivastava, Niloo; Manvati, Siddharth; Srivastava, Archita; Pal, Ranjana; Kalaiarasan, Ponnusamy; Chattopadhyay, Shilpi; Gochhait, Sailesh; Dua, Raina; Bamezai, Rameshwar N K

2011-04-04

New levels of gene regulation with microRNA (miR) and gene copy number alterations (CNAs) have been identified as playing a role in various cancers. We have previously reported that sporadic breast cancer tissues exhibit significant alteration in H2AX gene copy number. However, how CNA affects gene expression and what is the role of miR, miR-24-2, known to regulate H2AX expression, in the background of the change in copy number, are not known. Further, many miRs, including miR-24-2, are implicated as playing a role in cell proliferation and apoptosis, but their specific target genes and the pathways contributing to them remain unexplored. Changes in gene copy number and mRNA/miR expression were estimated using real-time polymerase chain reaction assays in two mammalian cell lines, MCF-7 and HeLa, and in a set of sporadic breast cancer tissues. In silico analysis was performed to find the putative target for miR-24-2. MCF-7 cells were transfected with precursor miR-24-2 oligonucleotides, and the gene expression levels of BRCA1, BRCA2, ATM, MDM2, TP53, CHEK2, CYT-C, BCL-2, H2AFX and P21 were examined using TaqMan gene expression assays. Apoptosis was measured by flow cytometric detection using annexin V dye. A luciferase assay was performed to confirm BCL-2 as a valid cellular target of miR-24-2. It was observed that H2AX gene expression was negatively correlated with miR-24-2 expression and not in accordance with the gene copy number status, both in cell lines and in sporadic breast tumor tissues. Further, the cells overexpressing miR-24-2 were observed to be hypersensitive to DNA damaging drugs, undergoing apoptotic cell death, suggesting the potentiating effect of mir-24-2-mediated apoptotic induction in human cancer cell lines treated with anticancer drugs. BCL-2 was identified as a novel cellular target of miR-24-2. mir-24-2 is capable of inducing apoptosis by modulating different apoptotic pathways and targeting BCL-2, an antiapoptotic gene. The study suggests that miR-24-2 is more effective in controlling H2AX gene expression, regardless of the change in gene copy number. Further, the study indicates that combination therapy with miR-24-2 along with an anticancer drug such as cisplatin could provide a new avenue in cancer therapy for patients with tumors otherwise resistant to drugs.

Cognitive control in context: working memory capacity and proactive control.

PubMed

Redick, Thomas S

2014-01-01

Working memory is important for maintaining critical information in an active state to guide future behavior. The executive-attention theory of working memory capacity (WMC; Engle & Kane, 2004) argues that goal maintenance is important for response selection when stimuli are associated with competing responses. Braver, Burgess, and Gray (2007) have labeled this type of preparatory activity proactive control. Previous WMC studies have not allowed individuals to use goal information to prepare a specific response in advance of the stimulus. The current experiment used different versions of a cue-probe task to examine the relationship between individual differences in WMC and proactive control. Across three versions of the AX version of the Continuous Performance Test, the proportion of targets was manipulated to affect both the predictive validity of the A cue and the prepotency of the target response to X probes. The results indicated that the high-WMC individuals used the cue information to prepare responses in advance only when a specific probe was likely to occur. In contrast, the performance of the low-WMC individuals was less dependent upon the cue and more contingent upon overall response frequencies. The results indicate that individual differences in WMC are related to proactive control and anticipation, and important for translating cognition into action. © 2013 Elsevier B.V. All rights reserved.

Defining the Biological Effectiveness of Components of High-LET Track Structure.

PubMed

Sridharan, Deepa M; Chappell, Lori J; Whalen, Mary K; Cucinotta, Francis A; Pluth, Janice M

2015-07-01

During space travel, astronauts are exposed to a wide array of high-linear energy transfer (LET) particles, with differing energies and resulting biological effects. Risk assessment of these exposures carries a large uncertainty predominantly due to the unique track structure of the particle's energy deposition. The complex damage elicited by high charge and energy (HZE) particles results from both lesions along the track core and from energetic electrons, δ rays, generated as a consequence of particle traversal. To better define how cells respond to this complex radiation exposure, a normal hTERT immortalized skin fibroblast cell line was exposed to a defined panel of particles carefully chosen to tease out track structure effects. Phosphorylation kinetics for several key double-strand break (DSB) response proteins (γ-H2AX, pATF2 and pSMC1) were defined after exposure to ten different high-LET radiation qualities and one low-LET radiation (X ray), at two doses (0.5-2 Gy) and time points (2 and 24 h). The results reveal that the lower energy particles (Fe 300, Si 93 and Ti 300 MeV/u), with a narrower track width and higher number and intensity of δ rays, cause the highest degree of persistent damage response. The persistent γ-H2AX signal at lower energies suggests that damage from these exposures are more difficult to resolve, likely due to the greater complexity of the associated DNA lesions. However, different kinetics were observed for the solely ATM-mediated phosphorylations (pATF2 and pSMC1), revealing a shallow induction at early times and a higher level of residual phosphorylation compared to γ-H2AX. The differing phospho-protein profiles exhibited, compared to γ-H2AX, suggests additional functions for these proteins within the cell. The strong correspondence between the predicted curves for energy deposition per nucleosome for each ion/energy combination and the persistent levels of γ-H2AX indicates that the nature of energy distribution defines residual levels of γ-H2AX, an indicator of unrepaired DSBs. Our results suggest that decreasing the energy of a particle results in more complex damage that may increase genomic instability and increase the risk of carcinogenesis.

Oxidative changes and apoptosis induced by 1800-MHz electromagnetic radiation in NIH/3T3 cells.

PubMed

Hou, Qingxia; Wang, Minglian; Wu, Shuicai; Ma, Xuemei; An, Guangzhou; Liu, Huan; Xie, Fei

2015-03-01

To investigate the potential adverse effects of mobile phone radiation, we studied reactive oxygen species (ROS), DNA damage and apoptosis in mouse embryonic fibroblasts (NIH/3T3) after intermittent exposure (5 min on/10 min off, for various durations from 0.5 to 8 h) to an 1800-MHz GSM-talk mode electromagnetic radiation (EMR) at an average specific absorption rate of 2 W/kg. A 2',7'-dichlorofluorescin diacetate fluorescence probe was used to detect intracellular ROS levels, immunofluorescence was used to detect γH2AX foci as a marker for DNA damage, and flow cytometry was used to measure apoptosis. Our results showed a significant increase in intracellular ROS levels after EMR exposure and it reached the highest level at an exposure time of 1 h (p < 0.05) followed by a slight decrease when the exposure continued for as long as 8 h. No significant effect on the number of γH2AX was detected after EMR exposure. The percentage of late-apoptotic cells in the EMR-exposed group was significantly higher than that in the sham-exposed groups (p < 0.05). These results indicate that an 1800-MHz EMR enhances ROS formation and promotes apoptosis in NIH/3T3 cells.

Thin Films

NASA Astrophysics Data System (ADS)

Khorshidi, Zahra; Bahari, Ali; Gholipur, Reza

2014-11-01

Effect of annealing temperature on the characteristics of sol-gel-driven Ta ax La(1- a) x O y thin film spin-coated on Si substrate as a high- k gate dielectric was studied. Ta ax La(1- a) x O y thin films with different amounts of a were prepared (as-prepared samples). X-ray diffraction measurements of the as-prepared samples indicated that Ta0.3 x La0.7 x Oy film had an amorphous structure. Therefore, Ta0.3 x La0.7 x O y film was chosen to continue the present studies. The morphology of Ta0.3 x La0.7 x O y films was studied using scanning electron microscopy and atomic force microscopy techniques. The obtained results showed that the size of grain boundaries on Ta0.3 x La0.7 x O y film surfaces was increased with increasing annealing temperature. Electrical and optical characterizations of the as-prepared and annealed films were investigated as a function of annealing temperature using capacitance-voltage ( C- V) and current density-voltage ( J- V) measurements and the Tauc method. The obtained results demonstrated that Ta0.3 x La0.7 x O y films had high dielectric constant (≈27), wide band gap (≈4.5 eV), and low leakage current density (≈10-6 A/cm2 at 1 V).

Thrust Augmenting Ejectors

DTIC Science & Technology

1975-06-01

approximately four . Presently referred to as the hypermixing nozzle (See Figure 37). d. Alternating exit nozzle - same as c, but the elemental aspect ratio...UL 0 Reynolds number, defined as R . In addition, due to the double symmetry about the y and z axes, the analysis will treat only one quadrant of the...in the duct of diffuser. Then from the conservation of mass A~x Atx) where A(x) g(x) tl(x) is the streamwise area distribution in one quadrant

DNA Repair Alterations in Children With Pediatric Malignancies: Novel Opportunities to Identify Patients at Risk for High-Grade Toxicities

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

Ruebe, Claudia E., E-mail: claudia.ruebe@uks.e; Fricke, Andreas; Schneider, Ruth

Purpose: To evaluate, in a pilot study, the phosphorylated H2AX ({gamma}H2AX) foci approach for identifying patients with double-strand break (DSB) repair deficiencies, who may overreact to DNA-damaging cancer therapy. Methods and Materials: The DSB repair capacity of children with solid cancers was analyzed compared with that of age-matched control children and correlated with treatment-related normal-tissue responses (n = 47). Double-strand break repair was investigated by counting {gamma}H2AX foci in blood lymphocytes at defined time points after irradiation of blood samples. Results: Whereas all healthy control children exhibited proficient DSB repair, 3 children with tumors revealed clearly impaired DSB repair capacities,more » and 2 of these repair-deficient children developed life-threatening or even lethal normal-tissue toxicities. The underlying mutations affecting regulatory factors involved in DNA repair pathways were identified. Moreover, significant differences in mean DSB repair capacity were observed between children with tumors and control children, suggesting that childhood cancer is based on genetic alterations affecting DSB repair function. Conclusions: Double-strand break repair alteration in children may predispose to cancer formation and may affect children's susceptibility to normal-tissue toxicities. Phosphorylated H2AX analysis of blood samples allows one to detect DSB repair deficiencies and thus enables identification of children at risk for high-grade toxicities.« less

Identification of peptidases in highly pathogenic vs. weakly pathogenic Naegleria fowleri amebae.

PubMed

Vyas, Ishan K; Jamerson, Melissa; Cabral, Guy A; Marciano-Cabral, Francine

2015-01-01

Naegleria fowleri, a free-living ameba, is the causative agent of Primary Amebic Meningoencephalitis. Highly pathogenic mouse-passaged amebae (Mp) and weakly pathogenic axenically grown (Ax) N. fowleri were examined for peptidase activity. Zymography and azocasein peptidase activity assays demonstrated that Mp and Ax N. fowleri exhibited a similar peptidase pattern. Prominent for whole cell lysates, membranes and conditioned medium (CM) from Mp and Ax amebae was the presence of an activity band of approximately 58 kDa that was sensitive to E64, a cysteine peptidase inhibitor. However, axenically grown N. fowleri demonstrated a high level of this peptidase activity in membrane preparations. The inhibitor E64 also reduced peptidase activity in ameba-CM consistent with the presence of secreted cysteine peptidases. Exposure of Mp amebae to E64 reduced their migration through matrigel that was used as an extracellular matrix, suggesting a role for cysteine peptidases in invasion of the central nervous system (CNS). The collective results suggest that the profile of peptidases is not a discriminative marker for distinguishing Mp from Ax N. fowleri. However, the presence of a prominent level of activity for cysteine peptidases in N. fowleri membranes and CM, suggests that these enzymes may serve to facilitate passage of the amebae into the CNS. © 2014 The Author(s) Journal of Eukaryotic Microbiology © 2014 International Society of Protistologists.

3D-structured illumination microscopy reveals clustered DNA double-strand break formation in widespread γH2AX foci after high LET heavy-ion particle radiation.

PubMed

Hagiwara, Yoshihiko; Niimi, Atsuko; Isono, Mayu; Yamauchi, Motohiro; Yasuhara, Takaaki; Limsirichaikul, Siripan; Oike, Takahiro; Sato, Hiro; Held, Kathryn D; Nakano, Takashi; Shibata, Atsushi

2017-12-12

DNA double-strand breaks (DSBs) induced by ionising radiation are considered the major cause of genotoxic mutations and cell death. While DSBs are dispersed throughout chromatin after X-rays or γ-irradiation, multiple types of DNA damage including DSBs, single-strand breaks and base damage can be generated within 1-2 helical DNA turns, defined as a complex DNA lesion, after high Linear Energy Transfer (LET) particle irradiation. In addition to the formation of complex DNA lesions, recent evidence suggests that multiple DSBs can be closely generated along the tracks of high LET particle irradiation. Herein, by using three dimensional (3D)-structured illumination microscopy, we identified the formation of 3D widespread γH2AX foci after high LET carbon-ion irradiation. The large γH2AX foci in G 2 -phase cells encompassed multiple foci of replication protein A (RPA), a marker of DSBs undergoing resection during homologous recombination. Furthermore, we demonstrated by 3D analysis that the distance between two individual RPA foci within γH2AX foci was approximately 700 nm. Together, our findings suggest that high LET heavy-ion particles induce clustered DSB formation on a scale of approximately 1 μm 3 . These closely localised DSBs are considered to be a risk for the formation of chromosomal rearrangement after heavy-ion irradiation.

Hairline fractures following volar plating of the distal radius: a recently recognized hardware-related complication.

PubMed

Otremski, Hila; Dolkart, Oleg; Atlan, Franck; Hutt, Dan; Segev, Elad; Pritsch, Tamir; Rosenblatt, Yishai

2018-06-01

Intraoperative hairline longitudinal fractures were recently reported in association with distal radius volar plating. Our aim was to further analyze this newly described complication. A retrospective radiographic and chart review was performed on 225 patients who underwent distal radius plating between June 2013 and June 2015. The Acu-Loc/Acu-Loc2© plating system (Acumed, Hillsboro, OR, USA) was used in 208 cases, and the VariAx© plating system (Stryker, Kalamazoo, MI, USA) was used in 17 cases. Three independent reviewers performed a blind evaluation of all relevant radiographs for the occurrence of longitudinal fractures around the plate, and validity was considered only when there was agreement among all three of them. Hairline longitudinal fractures were identified in 57 cases (25%), 55 with the Acu-Loc/Acu-Loc2© system and 2 with the VariAx© system. All fractures occurred with volar plating. Fracture occurrence was associated with age over 59 years, female gender, extra-articular fractures, and the use of Hexalobe screws (Acu-Loc/Acu-Loc2© system). We believe that the source of fracture occurrence lies within the screw design and that better screw design and possibly tapping in patients at risk may reduce the occurrence of intraoperative hairline longitudinal fractures. Further clinical and biomechanical research is needed to better understand this newly reported complication.

Number Theoretic Background

NASA Astrophysics Data System (ADS)

Rudnick, Z.

Contents: 1. Introduction 2. Divisibility 2.1. Basics on Divisibility 2.2. The Greatest Common Divisor 2.3. The Euclidean Algorithm 2.4. The Diophantine Equation ax+by=c 3. Prime Numbers 3.1. The Fundamental Theorem of Arithmetic 3.2. There Are Infinitely Many Primes 3.3. The Density of Primes 3.4. Primes in Arithmetic Progressions 4. Continued Fractions 5. Modular Arithmetic 5.1. Congruences 5.2. Modular Inverses 5.3. The Chinese Remainder Theorem 5.4. The Structure of the Multiplicative Group (Z/NZ)^* 5.5. Primitive Roots 6. Quadratic Congruences 6.1. Euler's Criterion 6.2. The Legendre Symbol and Quadratic Reciprocity 7. Pell's Equation 7.1. The Group Law 7.2. Integer Solutions 7.3. Finding the Fundamental Solution 8. The Riemann Zeta Function 8.1 Analytic Continuation and Functinal Equation of ζ(s) 8.2 Connecting the Primes and the Zeros of ζ(s) 8.3 The Riemann Hypothesis References

Gadolinium-enhanced cardiac MR exams of human subjects are associated with significant increases in the DNA repair marker 53BP1, but not the damage marker γH2AX

PubMed Central

McDonald, Robert J.; Ekins, Jacob B.; Tin, Anthony S.; Costes, Sylvain; Hudson, Tamara M.; Schroeder, Dana J.; Kallmes, Kevin; Kaufmann, Scott H.; Young, Philip M.; Lu, Aiming; Kadirvel, Ramanathan; Kallmes, David F.

2018-01-01

Magnetic resonance imaging is considered low risk, yet recent studies have raised a concern of potential damage to DNA in peripheral blood leukocytes. This prospective Institutional Review Board-approved study examined potential double-strand DNA damage by analyzing changes in the DNA damage and repair markers γH2AX and 53BP1 in patients who underwent a 1.5 T gadolinium-enhanced cardiac magnetic resonance (MR) exam. Sixty patients were enrolled (median age 55 years, 39 males). Patients with history of malignancy or who were receiving chemotherapy, radiation therapy, or steroids were excluded. MR sequence data were recorded and blood samples obtained immediately before and after MR exposure. An automated immunofluorescence assay quantified γH2AX or 53BP1 foci number in isolated peripheral blood mononuclear cells. Changes in foci number were analyzed using the Wilcoxon signed-rank test. Clinical and MR procedural characteristics were compared between patients who had a >10% increase in γH2AX or 53BP1 foci numbers and patients who did not. The number of γH2AX foci did not significantly change following cardiac MR (median foci per cell pre-MR = 0.11, post-MR = 0.11, p = .90), but the number of 53BP1 foci significantly increased following MR (median foci per cell pre-MR = 0.46, post-MR = 0.54, p = .0140). Clinical and MR characteristics did not differ significantly between patients who had at least a 10% increase in foci per cell and those who did not. We conclude that MR exposure leads to a small (median 25%) increase in 53BP1 foci, however the clinical relevance of this increase is unknown and may be attributable to normal variation instead of MR exposure. PMID:29309426

The contribution of DNA replication stress marked by high-intensity, pan-nuclear γH2AX staining to chemosensitization by CHK1 and WEE1 inhibitors.

PubMed

Parsels, Leslie A; Parsels, Joshua D; Tanska, Daria M; Maybaum, Jonathan; Lawrence, Theodore S; Morgan, Meredith A

2018-06-12

Small molecule inhibitors of the checkpoint proteins CHK1 and WEE1 are currently in clinical development in combination with the antimetabolite gemcitabine. It is unclear, however, if there is a therapeutic advantage to CHK1 vs. WEE1 inhibition for chemosensitization. The goals of this study were to directly compare the relative efficacies of the CHK1 inhibitor MK8776 and the WEE1 inhibitor AZD1775 to sensitize pancreatic cancer cell lines to gemcitabine and to identify pharmacodynamic biomarkers predictive of chemosensitization. Cells treated with gemcitabine and either MK8776 or AZD1775 were first assessed for clonogenic survival. With the exception of the homologous recombination-defective Capan1 cells, which were relatively insensitive to MK8776, we found that these cell lines were similarly sensitized to gemcitabine by CHK1 or WEE1 inhibition. The abilities of either the CDK1/2 inhibitor roscovitine or exogenous nucleosides to prevent MK8776 or AZD1775-mediated chemosensitization, however, were both inhibitor-dependent and variable among cell lines. Given the importance of DNA replication stress to gemcitabine chemosensitization, we next assessed high-intensity, pan-nuclear γH2AX staining as a pharmacodynamic marker for sensitization. In contrast to total γH2AX, aberrant mitotic entry or sub-G1 DNA content, high-intensity γH2AX staining correlated with chemosensitization by either MK8776 or AZD1775 (R 2 0.83 - 0.53). In summary, we found that MK8776 and AZD1775 sensitize to gemcitabine with similar efficacy. Furthermore, our results suggest that the effects of CHK1 and WEE1 inhibition on gemcitabine-mediated replication stress best predict chemosensitization and support the use of high-intensity or pan-nuclear γH2AX staining as a marker for therapeutic response.

Manual versus automated γ-H2AX foci analysis across five European laboratories: can this assay be used for rapid biodosimetry in a large scale radiation accident?

PubMed

Rothkamm, Kai; Barnard, Stephen; Ainsbury, Elizabeth A; Al-Hafidh, Jenna; Barquinero, Joan-Francesc; Lindholm, Carita; Moquet, Jayne; Perälä, Marjo; Roch-Lefèvre, Sandrine; Scherthan, Harry; Thierens, Hubert; Vral, Anne; Vandersickel, Veerle

2013-08-30

The identification of severely exposed individuals and reassurance of the 'worried well' are of prime importance for initial triage following a large scale radiation accident. We aim to develop the γ-H2AX foci assay into a rapid biomarker tool for use in accidents. Here, five laboratories established a standard operating procedure and analysed 100 ex vivo γ-irradiated, 4 or 24h incubated and overnight-shipped lymphocyte samples from four donors to generate γ-H2AX reference data, using manual and/or automated foci scoring strategies. In addition to acute, homogeneous exposures to 0, 1, 2 and 4Gy, acute simulated partial body (4Gy to 50% of cells) and protracted exposures (4Gy over 24h) were analysed. Data from all laboratories could be satisfactorily fitted with linear dose response functions. Average yields observed at 4h post exposure were 2-4 times higher than at 24h and varied considerably between laboratories. Automated scoring caused larger uncertainties than manual scoring and was unable to identify partial exposures, which were detectable in manually scored samples due to their overdispersed foci distributions. Protracted exposures were detectable but doses could not be accurately estimated with the γ-H2AX assay. We conclude that the γ-H2AX assay may be useful for rapid triage following a recent acute radiation exposure. The potentially higher speed and convenience of automated relative to manual foci scoring needs to be balanced against its compromised accuracy and inability to detect partial body exposures. Regular re-calibration or inclusion of reference samples may be necessary to ensure consistent results between laboratories or over long time periods. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Gender Differences in Axial Spondyloarthritis: Women Are Not So Lucky.

PubMed

Rusman, T; van Vollenhoven, R F; van der Horst-Bruinsma, I E

2018-05-12

Ankylosing spondylitis (AS) was historically seen as a predominantly male disease. However, more recent data showed a more homogenous sex prevalence. Unfortunately, in many studies in axial spondyloarthritis (axSpA), the number of women included is low and the analyses are often not stratified for gender distribution. The purpose of this review is to aggregate the existing data on gender differences in axSpA in order to increase the awareness that female axSpA patients are still under-recognized. Several studies considering gender differences revealed that female axSpA patients had different disease manifestations due to different immunological, hormonal, and genetic responses. For instance, allelic frequencies of the AHNK-gene and tissue non-specific alkaline phosphatase (TNAP) haplotypes differed between men and women with ankylosing spondylitis (AS). In addition, different levels of tumor necrosis factor (TNF), interleukins IL-6, IL-17, and IL-18, were found between the two sexes. Furthermore, female patients show a higher diagnostic delay compared to males. Several studies indicate a higher frequency of extra-articular manifestations (EAM) in female axSpA patients, such as enthesitis, psoriasis, and inflammatory bowel disease (IBD), whereas acute anterior uveitis is more prevalent in male patients. Male AS patients more frequently show a higher Bath Ankylosing Spondylitis Radiology Index (BASRI) scores and modified Stoke Ankylosing Spondylitis Spine Scores (mSASSS) than females, which indicates that males have higher radiological damage and radiographic progression. However, disease activity (BASDAI) and quality of life (AsQol) scores are significantly higher in women, and more importantly, they have significantly lower response rates to treatment with TNF inhibitors (TNFi) and a significantly lower drug adherence. Despite the fact that men with axial SpA have a worse radiologic prognosis, women have a high disease burden, in part because they have a longer delay in diagnosis, higher disease activity, and significantly less responsiveness to treatment with TNFi.

An Assessment in SpondyloArthritis International Society (ASAS)-endorsed definition of clinically important worsening in axial spondyloarthritis based on ASDAS.

PubMed

Molto, Anna; Gossec, Laure; Meghnathi, Bhowmik; Landewé, Robert B M; van der Heijde, Désirée; Atagunduz, Pamir; Elzorkany, Bassel Kamal; Akkoc, Nurullah; Kiltz, Uta; Gu, Jieruo; Wei, James Cheng Chung; Dougados, Maxime

2018-01-01

In a previous phase, 12 draft definitions for clinically important worsening in axial spondyloarthritis (axSpA) were selected, of which 3 were based on absolute changes in Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP (ASDAS). The objective here was to select the best cut-off for ASDAS for clinically important worsening in axSpA for use in clinical trials and observational studies. An international longitudinal prospective study evaluating stable patients with axSpA was conducted. Data necessary to calculate ASDAS were collected at two consecutive visits (spaced 7 days to 6 months). Sensitivity and specificity of the three cut-offs for change in ASDAS were tested against the patient's subjective assessment of worsening as the external standard (ie, the patient reporting that he had worsened and felt a need for treatment intensification). Final selection was made by a consensus and voting procedure among Assessment of SpondyloArthritis International Society (ASAS) members. In total, 1169 patients with axSpA were analysed: 64.8% were male and had a mean age of 41.7 (SD 12.4) years. At the second visit, 127 (10.9%) patients judged their situation as worsened.Sensitivity and specificity for an increase of at least 0.6, 0.9 and 1.1 ASDAS points to detect patient-reported worsening were 0.55 (Se) and 0.91 (Sp), 0.38 (Se) and 0.96 (Sp), and 0.33 (Se) and 0.98 (Sp), respectively. The ASAS consensus was to define clinically important worsening as an increase in ASDAS of at least 0.9 points. This data-driven ASAS consensus process resulted in an ASDAS-based cut-off value defining clinically important worsening in axSpA for use in trials. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Sedative and cardiorespiratory effects of low doses of xylazine with and without acepromazine in Nordestino donkeys.

PubMed

Lucas Castillo, J A; Gozalo-Marcilla, M; Werneck Fonseca, M; Possebon, F S; da Rosa, A C; de Araujo Aguiar, A J

2018-03-22

Information on appropriate protocols for sedation of Nordestino donkeys is scarce. To evaluate the sedative and cardiorespiratory effects of low doses of intravenous (i.v.) xylazine with and without acepromazine in 'Nordestino' donkeys. Seven healthy female Nordestino donkeys (150 ± 18 kg) were included in this blinded, randomised, crossover experiment. Four treatments were administered, consisting of two i.v. injections, at baseline (T0, 1st injection) and 15 min later (T15, 2nd injection). Treatments included acepromazine 0.05 mg/kg bwt + saline (AS), saline + xylazine 0.5 mg/kg bwt (SX0.5), acepromazine + xylazine 0.25 mg/kg bwt (AX0.25) or acepromazine + xylazine 0.5 mg/kg bwt (AX0.5). Sedative and cardiorespiratory parameters were evaluated before T0 and 15, 20, 30, 45, 60, 75 and 90 min after treatment. Degree [height of head above ground (HHAG)] and quality of sedation [ataxia, responses to stimuli and visual analogue scale (VAS) scoring] and respiratory rate were evaluated by the main investigator in situ, and heart rate was measured by an assistant investigator. Three experienced evaluators assessed vídeos for ataxia and responses to stimuli. Normal data were analysed by repeated measures ANOVA, and non-normal by Kruskal-Wallis (P<0.05). HHAG was lower than baseline for 15 min after xylazine administration in AX0.25 and for 30 min in SX0.5 and AX0.5 groups. All treatments with xylazine increased VAS and ataxia scores in situ for 15 min after xylazine administration, with no differences between groups. Ataxia scores in situ were higher in SX0.5 and AX0.5 groups than AS for 15 and 30 min after xylazine administration, respectively. Absence of a negative control group (saline-saline). Acepromazine added to xylazine at 0.25 mg/kg bwt produced briefer and milder sedation than xylazine at 0.5 mg/kg bwt. © 2018 EVJ Ltd.

Gamma-H2AX-based dose estimation for whole and partial body radiation exposure.

PubMed

Horn, Simon; Barnard, Stephen; Rothkamm, Kai

2011-01-01

Most human exposures to ionising radiation are partial body exposures. However, to date only limited tools are available for rapid and accurate estimation of the dose distribution and the extent of the body spared from the exposure. These parameters are of great importance for emergency triage and clinical management of exposed individuals. Here, measurements of γ-H2AX immunofluorescence by microscopy and flow cytometry were compared as rapid biodosimetric tools for whole and partial body exposures. Ex vivo uniformly X-irradiated blood lymphocytes from one donor were used to generate a universal biexponential calibration function for γ-H2AX foci/intensity yields per unit dose for time points up to 96 hours post exposure. Foci--but not intensity--levels remained significantly above background for 96 hours for doses of 0.5 Gy or more. Foci-based dose estimates for ex vivo X-irradiated blood samples from 13 volunteers were in excellent agreement with the actual dose delivered to the targeted samples. Flow cytometric dose estimates for X-irradiated blood samples from 8 volunteers were in excellent agreement with the actual dose delivered at 1 hour post exposure but less so at 24 hours post exposure. In partial body exposures, simulated by mixing ex vivo irradiated and unirradiated lymphocytes, foci/intensity distributions were significantly over-dispersed compared to uniformly irradiated lymphocytes. For both methods and in all cases the estimated fraction of irradiated lymphocytes and dose to that fraction, calculated using the zero contaminated Poisson test and γ-H2AX calibration function, were in good agreement with the actual mixing ratios and doses delivered to the samples. In conclusion, γ-H2AX analysis of irradiated lymphocytes enables rapid and accurate assessment of whole body doses while dispersion analysis of foci or intensity distributions helps determine partial body doses and the irradiated fraction size in cases of partial body exposures.

Synthesis of [Fe(Leq)(Lax)] n coordination polymer nanoparticles using blockcopolymer micelles.

PubMed

Göbel, Christoph; Klimm, Ottokar; Puchtler, Florian; Rosenfeldt, Sabine; Förster, Stephan; Weber, Birgit

2017-01-01

Spin-crossover compounds are a class of materials that can change their spin state from high spin (HS) to low spin (LS) by external stimuli such as light, pressure or temperature. Applications demand compounds with defined properties concerning the size and switchability that are maintained when the compound is integrated into composite materials. Here, we report the synthesis of [Fe(L eq )(L ax )] n coordination polymer (CP) nanoparticles using self-assembled polystyrene- block -poly(4-vinylpyridine) (PS- b -P4VP) block copolymer (BCP) micelles as template. Variation of the solvent (THF and toluene) and the rigidity of the axial ligand L ax (L ax = 1,2-di(pyridin-4-yl)ethane) (bpea), trans -1,2-di(pyridin-4-yl)ethene (bpee), and 1,2-di(pyridin-4-yl)ethyne) (bpey); L eq = 1,2-phenylenebis(iminomethylidyne)-bis(2,4-pentanedionato)(2-)) allowed the determination of the preconditions for the selective formation of nanoparticles. A low solubility of the CP in the used solvent and a high stability of the Fe-L bond with regard to ligand exchange are necessary for the formation of composite nanoparticles where the BCP micelle is filled with the CP, as in the case of the [FeL eq (bpey)] n @BCP. Otherwise, in the case of more flexible ligands or ligands that lead to high spin complexes, the formation of microcrystals next to the CP-BCP nanoparticles is observed above a certain concentration of [Fe(L eq )(L ax )] n . The core of the nanoparticles is about 45 nm in diameter due to the templating effect of the BCP micelle, independent of the used iron complex and [Fe(L eq )(L ax )] n concentration. The spin-crossover properties of the composite material are similar to those of the bulk for FeL eq (bpea)] n @BCP while pronounced differences are observed in the case of [FeL eq (bpey)] n @BCP nanoparticles.

Biodosimetry Based on γ-H2AX Quantification and Cytogenetics after Partial- and Total-Body Irradiation during Fractionated Radiotherapy.

PubMed

Zahnreich, Sebastian; Ebersberger, Anne; Kaina, Bernd; Schmidberger, Heinz

2015-04-01

The aim of this current study was to quantitatively describe radiation-induced DNA damage and its distribution in leukocytes of cancer patients after fractionated partial- or total-body radiotherapy. Specifically, the impact of exposed anatomic region and administered dose was investigated in breast and prostate cancer patients receiving partial-body radiotherapy. DNA double-strand breaks (DSBs) were quantified by γ-H2AX immunostaining. The frequency of unstable chromosomal aberrations in stimulated lymphocytes was also determined and compared with the frequency of DNA DSBs in the same samples. The frequency of radiation-induced DNA damage was converted into dose, using ex vivo generated calibration curves, and was then compared with the administered physical dose. This study showed that 0.5 h after partial-body radiotherapy the quantity of radiation-induced γ-H2AX foci increased linearly with the administered equivalent whole-body dose for both tumor entities. Foci frequencies dropped 1 day thereafter but proportionality to the equivalent whole-body dose was maintained. Conversely, the frequency of radiation-induced cytogenetic damage increased from 0.5 h to 1 day after the first partial-body exposure with a linear dependence on the administered equivalent whole-body dose, for prostate cancer patients only. Only γ-H2AX foci assessment immediately after partial-body radiotherapy was a reliable measure of the expected equivalent whole-body dose. Local tumor doses could be approximated with both assays after one day. After total-body radiotherapy satisfactory dose estimates were achieved with both assays up to 8 h after exposure. In conclusion, the quantification of radiation-induced γ-H2AX foci, but not cytogenetic damage in peripheral leukocytes was a sensitive and rapid biodosimeter after acute heterogeneous irradiation of partial body volumes that was able to primarily assess the absorbed equivalent whole-body dose.

Ultrasound-guided axillary brachial plexus block versus local infiltration anesthesia for arteriovenous fistula creation at the forearm for hemodialysis in patients with chronic renal failure.

PubMed

Nofal, W H; El Fawal, S M; Shoukry, A A; Sabek, Eas; Malak, Wfa

2017-01-01

The primary failure rate for arteriovenous fistula (AVF) creation under local anesthesia for hemodialysis is about 30%. Axillary brachial plexus block (BPB) may improve blood flow through blood vessels used in fistula creation; it may improve the AVF blood flow and thus may reduce the primary failure rate after 3 months. Hundred and forty patients with chronic renal failure scheduled for AVF creation for hemodialysis were divided into two equal groups; Group 1 (AxBP-G) received ultrasound (US) guided axillary BPB, and Group 2 (LI-G) received local infiltration. We recorded the measurements of the brachial and radial arteries before and after anesthesia and the AVF blood flow in both groups at three different time points. Furthermore, the primary failure rate was recorded in each group and compared. After anesthesia, the mean radial artery blood flow in the AxBP-group was 3.52 ml/min more than the LI-group, and the brachial artery diameter was also 0.68 mm more than in the LI-group, both differences were statistically significant ( P < 0.05). There were significant increases ( P < 0.05) in the AVF blood flow in the AxBP-group more than the LI-group with mean differences of 29.6, 69.8, and 27.2 ml/min at 4 h, 1 week, and 3 months, respectively. The overall mean of AVF blood flow was 42.21 ml/min more in the AxBP group than the LI-group a difference which is statistically significant ( P < 0.001). The primary failure rate was 17% in the AxBP group versus 30% in the LI-group; however, this difference is not significant statistically ( P = 0.110). The US-guided axillary block increases AVF blood flow significantly more than local infiltration and nonsignificantly decreases the primary failure rate of the AVF after 3 months.

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

Su, M; Sura, S

Purpose: To evaluate dosimetric impact of two axillary nodes (AX) boost techniques: (1) posterior-oblique optimized field boost (POB), (2) traditional posterior-anterior boost (PAB) with field optimization (O-PAB), for a postmastectomy breast patient with positive axillary lymph nodes. Methods: Five patients, 3 left and 2 right chest walls, were included in this study. All patients were simulated in 5mm CT slice thickness. Supraclavicular (SC) and level I/II/III AX were contoured based on the RTOG atlas guideline. Five treatment plans, (1) tangential chest wall, (2) oblique SC including AX, (3) PAB, O-PAB and POB, were created for each patient. Three plan sumsmore » (PS) were generated by sum one of (3) plan with plan (1) and (2). The field optimization was done through PS dose distribution, which included a field adjustment, a fractional dose, a calculation location and a gantry angle selection for POB. A dosimetric impact was evaluated by comparing a SC and AX coverage, a PS maximum dose, an irradiated area percentage volume received dose over 105% prescription dose (V105), an ipsi-laterial mean lung dose (MLD), an ipsi-laterial mean humeral head dose (MHHD), a mean heart dose (MHD) (for left case only) and their DVH amount these three technique. Results: O-PAB, POB and PAB dosimetric results showed that there was no significant different on SC and AX coverage (p>0.43) and MHD (p>0.16). The benefit of sparing lung irradiation from PAB to O-PAB to POB was significant (p<0.004). PAB showed a highest PS maximum dose (p<0.005), V105 (p<0.023) and MLD (compared with OPAB, p=0.055). MHHD showed very sensitive to the patient arm positioning and anatomy. O-PAB convinced a lower MHHD than PAB (p=0.03). Conclusion: 3D CT contouring plays main role in accuracy radiotherapy. Dosimetric advantage of POB and O-PAB was observed for a better normal tissue irradiation sparing.« less

Nonlinear Ocean Waves

DTIC Science & Technology

1993-01-12

work is the fact that the equation due to Kadomtsev & Petviashvili (1970), ax(atU + UaxU + a, 3 U) + ay2 U = 0, (KP) describes approximately the...B.B. Kadomtsev & V.1 Petviashvili , Soy. Phys. Doklady, 15, pp. 539- 541, 1970 NTI QRIA@lo310 For, STis GRAU ], DTIC TAB 0 jJUSo catzio DiSt AV ...numerical discretizations of the nonlinear Schr6dinger equation , i atV + axEV + 21VI2V = 0, (NLS) with periodic boundary conditions. This equation is a well

NS(B) (Nitrogen Sulfide (B State)) Spectrum Theory and Code

DTIC Science & Technology

1989-05-01

8217TRAhS’oTRWCNp laP) ,NIfIP C NOTE: EP- BPP <C FCF RED DEGRADED BANDS C PP- BPP >C FCF BLUE DEGRACED eANCS WRITEC3o*) *BP-EPPs’f9(NN*1,I)-8CNNpIP) 60... FMA X. GT .Ft!ACLC .AND .C FPA X1 /FMAX ) GT..2) THEN XPEAK (N,IoIP)=XI1 YP EAK (N.,!,IP) rnPA)I( PE AX(N, IIP) ,FPAX) FfAX CLD=F PAX ENDIF 5

Resolving the Orientation of Cylinders and Cuboids from Projected Area Measurements

DTIC Science & Technology

2016-05-01

fabs ( e1 ) + Ay * fabs ( e2...Az * fabs ( e3 ) - A_xy; 90 g = Ax * fabs ( e4 ) + Ay * fabs ( e5 ) + Az * fabs ( e6 ) - A_xz; 91 h = Ax * fabs ( e7 ) + Ay * fabs ( e8 ) + Az * fabs ( e9...b23 * h; 128 del_r = b31 * f + b32 * g + b33 * h; 129 130 p -= del_p; 131 y -= del_y; 132 r -= del_r; 133 134 if ( fabs ( del_p ) < TOL && fabs (

Massachusetts Institute of Technology Consortium Agreement. Phase II

DTIC Science & Technology

1999-03-01

Portable VOR Testing Apparatusthe visual target. Head movements are monitored with magneto-hydrodynamic rotational velocity sensors , and eye motions are...Zhang 4. Miniaturization of the Ring Sensor B-H Yang, H. Asada, K-W. Chang , S. Rhee, Y. Zhang 5. SIMSUIT and Biochair Projects L. Jones, J. Tangorra...No change along 0 a•0a = (2) Neglect Vr = Vr = 0 (Wall velocity of r direction is very small compared with v.’.) a ax ax= (3) As r << x, Dr• >> axx

Controlled release of astaxanthin from nanoporous silicified-phospholipids assembled boron nitride complex for cosmetic applications

NASA Astrophysics Data System (ADS)

Lee, Hye Sun; Sung, Dae Kyung; Kim, Sung Hyun; Choi, Won Il; Hwang, Ee Tag; Choi, Doo Jin; Chang, Jeong Ho

2017-12-01

Nanoporous silicified-phospholipids assembled boron nitride (nSPLs@BN) powder was prepared and demonstrated for use in controlled release of anti-oxidant astaxanthin (AX) as a cosmetic application. The nanoporous silicified phospholipids (nSPLs) were obtained by the silicification with tetraethyl orthosilicate (TEOS) of the hydrophilic region of phospholipid bilayers. This process involved the co-assembly of chemically active phospholipid bilayers within the porous silica matrix. In addition, nSPLs@BN was characterized using several analytical techniques and tested to assess their efficiency as drug delivery systems. We calculated the maximum release amounts as a function of time and various pH. The release rate of AX from the nSPLs@BN for the initial 24 h was 10.7 μmol/(h mg) at pH 7.4. Furthermore, we determined the antioxidant activity (KD) for the released AX with DPPH (1,1-diphenyl-2-picryl-hydrazyl) radical and the result was 34.6%.

Enhanced mobility CsPbI3 quantum dot arrays for record-efficiency, high-voltage photovoltaic cells

PubMed Central

Sanehira, Erin M.; Marshall, Ashley R.; Christians, Jeffrey A.; Harvey, Steven P.; Ciesielski, Peter N.; Wheeler, Lance M.; Schulz, Philip; Lin, Lih Y.; Beard, Matthew C.; Luther, Joseph M.

2017-01-01

We developed lead halide perovskite quantum dot (QD) films with tuned surface chemistry based on A-site cation halide salt (AX) treatments. QD perovskites offer colloidal synthesis and processing using industrially friendly solvents, which decouples grain growth from film deposition, and at present produce larger open-circuit voltages (VOC’s) than thin-film perovskites. CsPbI3 QDs, with a tunable bandgap between 1.75 and 2.13 eV, are an ideal top cell candidate for all-perovskite multijunction solar cells because of their demonstrated small VOC deficit. We show that charge carrier mobility within perovskite QD films is dictated by the chemical conditions at the QD-QD junctions. The AX treatments provide a method for tuning the coupling between perovskite QDs, which is exploited for improved charge transport for fabricating high-quality QD films and devices. The AX treatments presented here double the film mobility, enabling increased photocurrent, and lead to a record certified QD solar cell efficiency of 13.43%. PMID:29098184

On the nature of the symbiotic binary AX Persei

NASA Technical Reports Server (NTRS)

Mikolajewska, Joanna; Kenyon, Scott J.

1992-01-01

Photometric and spectroscopic observations of the symbiotic binary AX Persei are presented. This system contains a red giant that fills its tidal lobe and transfers material into an accretion disk surrounding a low-mass main-sequence star. The stellar masses - 1 solar mass for the red giant and about 0.4 solar mass for the companion - suggest AX Per is poised to enter a common envelope phase of evolution. The disk luminosity increases from L(disk) about 100 solar luminosity in quiescence to L(disk) about 5700 solar luminosity in outburst for a distance of d = 2.5 kpc. Except for visual maximum, high ionization permitted emission lines - such as He II - imply an EUV luminosity comparable to the disk luminosity. High-energy photons emitted by a hot boundary layer between the disk and central star ionize a surrounding nebula to produce this permitted line emission. High ionization forbidden lines form in an extended, shock-excited region well out of the binary's orbital plane and may be associated with mass loss from the disk.

Superconducting Sr 2- xAxCuO 2F 2+ δ( A=Ca, Ba): Synthetic Pathways and Associated Structural Rearrangements

NASA Astrophysics Data System (ADS)

Francesconi, M. G.; Slater, P. R.; Hodges, J. P.; Greaves, C.; Edwards, P. P.; Al-Mamouri, M.; Slaski, M.

1998-01-01

The low-temperature fluorination of a range of insulating alkaline earth cuprates Sr2-xAxCuO3(A=Ca (0≤x≤2);A=Ba (0≤x≤0.6)) can result in superconducting oxide fluorides Sr2-xAxCuO2F2+δ. In contrast, conventional high-temperature solid-state reactions produce thermodynamically more stable mixtures of oxides and fluorides. Various soft-chemistry fluorination pathways (utilizing F2gas, NH4F,MF2[M=Cu, Zn, Ni, Ag]) are compared with respect to their efficacy and mechanisms. Attention is also focused on the structural features of the mixed-oxide precursor and the final-oxide fluorides to highlight the remarkable structural rearrangements that occur during the low-temperature fluorination. The effects of fluorination of other Sr-Cu-O systems are used to identify the structural requirements of the precursor oxide in order to achieve such transformations.

Utility of γH2AX as a molecular marker of DNA double-strand breaks in nuclear medicine: applications to radionuclide therapy employing auger electron-emitting isotopes.

PubMed

Mah, Li-Jeen; Orlowski, Christian; Ververis, Katherine; El-Osta, Assam; Karagiannis, Tom C

2011-01-01

There is an intense interest in the development of radiopharmaceuticals for cancer therapy. In particular, radiopharmaceuticals which involve targeting radionuclides specifically to cancer cells with the use of monoclonal antibodies (radioimmunotherapy) or peptides (targeted radiotherapy) are being widely investigated. For example, the ultra-short range Auger electron-emitting isotopes, which are discussed in this review, are being considered in the context of DNAtargeted radiotherapy. The efficient quantitative evaluation of the levels of damage caused by such potential radiopharmaceuticals is required for assessment of therapeutic efficacy and determination of relevant doses for successful treatment. The DNA double-strand break surrogate marker, γH2AX, has emerged as a useful biomonitor of damage and thus effectiveness of treatment, offering a highly specific and sensitive means of assessment. This review will cover the potential applications of γH2AX in nuclear medicine, in particular radionuclide therapy.

Noise Adaptation and Correlated Maneuver Gating of an Extended Kalman Filter

DTIC Science & Technology

1990-03-01

ay. 89 - (V) 2 + VY2,,o (A.11) v t E(A21 Y )(V’~2 + V 20r8 2 (A. 12) We also find that the covariance of ax and ay is E[axay] - E[ aya j - Vic) -Y G... Diary -- YES eval([’ diary ’,MatFilename]); end; 108 % System Information, in continuous time, for target, and initial guess A=[0 1 00 % x 0000 % xdot 000...Cleanup diary off; 114 D. KFBR.M function [Z,GI,Res,Pxy,xe] = kfbr(xobs,zobs,xO,IE,A,B,W,V,T,MD,P0,RAI,IL,IT,SG) * %KF BR % [Z,GI,Res,Pxy,xe] - kf__br

How Does the Preparation of Rye Porridge Affect Molecular Weight Distribution of Extractable Dietary Fibers?

PubMed Central

Rakha, Allah; Åman, Per; Andersson, Roger

2011-01-01

Extractable dietary fiber (DF) plays an important role in nutrition. This study on porridge making with whole grain rye investigated the effect of rest time of flour slurries at room temperature before cooking and amount of flour and salt in the recipe on the content of DF components and molecular weight distribution of extractable fructan, mixed linkage (1→3)(1→4)-β-d-glucan (β-glucan) and arabinoxylan (AX) in the porridge. The content of total DF was increased (from about 20% to 23% of dry matter) during porridge making due to formation of insoluble resistant starch. A small but significant increase in the extractability of β-glucan (P = 0.016) and AX (P = 0.002) due to rest time was also noted. The molecular weight of extractable fructan and AX remained stable during porridge making. However, incubation of the rye flour slurries at increased temperature resulted in a significant decrease in extractable AX molecular weight. The molecular weight of extractable β-glucan decreased greatly during a rest time before cooking, most likely by the action of endogenous enzymes. The amount of salt and flour used in the recipe had small but significant effects on the molecular weight of β-glucan. These results show that whole grain rye porridge made without a rest time before cooking contains extractable DF components maintaining high molecular weights. High molecular weight is most likely of nutritional importance. PMID:21686191

How does the preparation of rye porridge affect molecular weight distribution of extractable dietary fibers?

PubMed

Rakha, Allah; Aman, Per; Andersson, Roger

2011-01-01

Extractable dietary fiber (DF) plays an important role in nutrition. This study on porridge making with whole grain rye investigated the effect of rest time of flour slurries at room temperature before cooking and amount of flour and salt in the recipe on the content of DF components and molecular weight distribution of extractable fructan, mixed linkage (1→3)(1→4)-β-d-glucan (β-glucan) and arabinoxylan (AX) in the porridge. The content of total DF was increased (from about 20% to 23% of dry matter) during porridge making due to formation of insoluble resistant starch. A small but significant increase in the extractability of β-glucan (P = 0.016) and AX (P = 0.002) due to rest time was also noted. The molecular weight of extractable fructan and AX remained stable during porridge making. However, incubation of the rye flour slurries at increased temperature resulted in a significant decrease in extractable AX molecular weight. The molecular weight of extractable β-glucan decreased greatly during a rest time before cooking, most likely by the action of endogenous enzymes. The amount of salt and flour used in the recipe had small but significant effects on the molecular weight of β-glucan. These results show that whole grain rye porridge made without a rest time before cooking contains extractable DF components maintaining high molecular weights. High molecular weight is most likely of nutritional importance.

The induction of thioredoxin-1 by epinephrine withdraws stress via interaction with β-arrestin-1

PubMed Central

Jia, Jin-Jing; Zeng, Xian-Si; Zhou, Xiao-Shuang; Li, Ye; Bai, Jie

2014-01-01

Stress regulates a panel of important physiological functions and disease states. Epinephrine is produced under stresses threaten to homeostasis. Thioredoxin-1(Trx-1) is a redox regulating protein which is induced to resist stresses and related with various diseases. Thus, it is important to examine whether Trx-1 is induced by epinephrine and to understand the underlying molecular mechanisms that Trx-1 modulates epinephrine stress. Here, we show that the expression of Trx-1 was induced by epinephrine via β-adrenergic receptor/Cyclic AMP/protein kinase A (PKA) signaling pathway in PC12 cells. The down-regulation of Trx-1 by siRNA aggravated accumulation of γ-H2AX and further decreased expression of p53 by epinephrine. Accordingly, Trx-1 overexpression alleviated accumulation of γ-H2AX and restored the expressions of p53 and C/EBP homologous protein (CHOP) in the cortex, hippocampus and thymus of mice. Moreover, Trx-1 overexpression reduced the malondialdehyde concentration by epinephrine. We further explored the mechanism on p53 and γ-H2AX regulated by Trx-1. We found that overexpression of Trx-1 suppressed β-arrestin-1 expression through interaction with β-arrestin-1. Consequently, the downregulation of β-arrestin-1 suppressed the cell viability and the expressions of γ-H2AX and cyclin D1, and increased p53 expression. Taken together, our data suggest that Trx-1/β-arrestin-1 interaction may represent a novel endogenous mechanism on protecting against stress. PMID:25486571

The bonding, charge distribution, spin ordering, optical, and elastic properties of four MAX phases Cr2AX (A = Al or Ge, X = C or N): From density functional theory study

NASA Astrophysics Data System (ADS)

Li, Neng; Mo, Yuxiang; Ching, Wai-Yim

2013-11-01

In this work, we assess a full spectrum of properties (chemical bonding, charge distribution, spin ordering, optical, and elastic properties) of Cr2AC (A = Al, Ge) and their hypothetical nitride counterparts Cr2AN (A = Al, Ge) based on density functional theory calculations. The calculated total energy values indicate that a variety of spin ordering of these four compounds depending on interlayer-interactions between M-A and M-X within the sublattice, which is supported by bonding analysis. MAX phase materials are discovered to possess exotic magnetic properties which indicates that these materials could serve as promising candidates for novel layered magnetic materials for various electronic and spintronic applications. Further analysis of optical properties for two polarization vectors of Cr2AX shows that the reflectivity is high in the visible-ultraviolet region up to ˜15 eV suggesting Cr2AX as a promising candidate for use as a coating material. The elastic coefficients (Cij) and bulk mechanical properties [bulk modulus (K), shear modulus (G), Young's modulus (E), Poisson's ratio (η), and Pugh ratio (G/K)] of these four Cr2AX compounds are also calculated and analyzed, which pave the way to predict or design new MAX phases that are less brittle or tougher by having a lower G/K value or higher η.

Alternative electron transports participate in the maintenance of violaxanthin De-epoxidase activity of Ulva sp. under low irradiance.

PubMed

Xie, Xiujun; Gu, Wenhui; Gao, Shan; Lu, Shan; Li, Jian; Pan, Guanghua; Wang, Guangce; Shen, Songdong

2013-01-01

The xanthophyll cycle (Xc), which involves violaxanthin de-epoxidase (VDE) and the zeaxanthin epoxidase (ZEP), is one of the most rapid and efficient responses of plant and algae to high irradiance. High light intensity can activate VDE to convert violaxanthin (Vx) to zeaxanthin (Zx) via antheraxanthin (Ax). However, it remains unclear whether VDE remains active under low light or dark conditions when there is no significant accumulation of Ax and Zx, and if so, how the ΔpH required for activation of VDE is built. In this study, we used salicylaldoxime (SA) to inhibit ZEP activity in the intertidal macro-algae Ulva sp. (Ulvales, Chlorophyta) and then characterized VDE under low light and dark conditions with various metabolic inhibitors. With inhibition of ZEP by SA, VDE remained active under low light and dark conditions, as indicated by large accumulations of Ax and Zx at the expense of Vx. When PSII-mediated linear electron transport systems were completely inhibited by SA and DCMU, alternative electron transport systems (i.e., cyclic electron transport and chlororespiration) could maintain VDE activity. Furthermore, accumulations of Ax and Zx decreased significantly when SA, DCMU, or DBMIB together with an inhibitor of chlororespiration (i.e., propyl gallate (PG)) were applied to Ulva sp. This result suggests that chlororespiration not only participates in the build-up of the necessary ΔpH, but that it also possibly influences VDE activity indirectly by diminishing the oxygen level in the chloroplast.

Alternative Electron Transports Participate in the Maintenance of Violaxanthin De-Epoxidase Activity of Ulva sp. under Low Irradiance

PubMed Central

Xie, Xiujun; Gu, Wenhui; Gao, Shan; Lu, Shan; Li, Jian; Pan, Guanghua; Wang, Guangce; Shen, Songdong

2013-01-01

The xanthophyll cycle (Xc), which involves violaxanthin de-epoxidase (VDE) and the zeaxanthin epoxidase (ZEP), is one of the most rapid and efficient responses of plant and algae to high irradiance. High light intensity can activate VDE to convert violaxanthin (Vx) to zeaxanthin (Zx) via antheraxanthin (Ax). However, it remains unclear whether VDE remains active under low light or dark conditions when there is no significant accumulation of Ax and Zx, and if so, how the ΔpH required for activation of VDE is built. In this study, we used salicylaldoxime (SA) to inhibit ZEP activity in the intertidal macro-algae Ulva sp. (Ulvales, Chlorophyta) and then characterized VDE under low light and dark conditions with various metabolic inhibitors. With inhibition of ZEP by SA, VDE remained active under low light and dark conditions, as indicated by large accumulations of Ax and Zx at the expense of Vx. When PSII-mediated linear electron transport systems were completely inhibited by SA and DCMU, alternative electron transport systems (i.e., cyclic electron transport and chlororespiration) could maintain VDE activity. Furthermore, accumulations of Ax and Zx decreased significantly when SA, DCMU, or DBMIB together with an inhibitor of chlororespiration (i.e., propyl gallate (PG)) were applied to Ulva sp. This result suggests that chlororespiration not only participates in the build-up of the necessary ΔpH, but that it also possibly influences VDE activity indirectly by diminishing the oxygen level in the chloroplast. PMID:24250793

Destruction of white matter integrity in patients with mild cognitive impairment and Alzheimer disease.

PubMed

Sun, Xiaoyan; Salat, David; Upchurch, Kristen; Deason, Rebecca; Kowall, Neil; Budson, Andrew

2014-10-01

Accumulating evidence shows that gradual loss of white matter integrity plays an important role in the development of Alzheimer disease (AD). The aim of this research was to study the microstructural integrity of white matter in AD in vivo. Global fractional anisotropy, global axial diffusivity (AxD), and global radial diffusivity (RD) were analyzed in subjects with normal controls (NC), mild cognitive impairment (MCI), and AD using Alzheimer's Disease Neuroimaging Initiative data (total N = 210). We further compared specific white matter tracts among the 3 groups. Compared with the NC group, the MCI group had significantly increased global AxD and global RD. Compared with the NC and MCI groups, the AD group had significantly decreased global fractional anisotropy, increased global AxD, and increased global RD. With regard to specific white matter tracts, in the MCI group, we found increased AxD and increased RD in the external capsule, part of the lateral cholinergic pathway, in addition to the tracts connecting the limbic regions, predominantly in the left hemisphere. In the AD group, white matter abnormalities were widespread, including in the external capsule (cholinergic pathway) and limbic region tracts as well as tracts connecting anterior to posterior regions bilaterally. The radiographic manifestation of damaged white matter microstructural integrity in the cholinergic pathway in MCI patients may provide a rational basis for the use of cholinesterase inhibitor drugs in the MCI stage of AD.

3D-structured illumination microscopy reveals clustered DNA double-strand break formation in widespread γH2AX foci after high LET heavy-ion particle radiation

PubMed Central

Hagiwara, Yoshihiko; Niimi, Atsuko; Isono, Mayu; Yamauchi, Motohiro; Yasuhara, Takaaki; Limsirichaikul, Siripan; Oike, Takahiro; Sato, Hiro; Held, Kathryn D.; Nakano, Takashi; Shibata, Atsushi

2017-01-01

DNA double-strand breaks (DSBs) induced by ionising radiation are considered the major cause of genotoxic mutations and cell death. While DSBs are dispersed throughout chromatin after X-rays or γ-irradiation, multiple types of DNA damage including DSBs, single-strand breaks and base damage can be generated within 1–2 helical DNA turns, defined as a complex DNA lesion, after high Linear Energy Transfer (LET) particle irradiation. In addition to the formation of complex DNA lesions, recent evidence suggests that multiple DSBs can be closely generated along the tracks of high LET particle irradiation. Herein, by using three dimensional (3D)-structured illumination microscopy, we identified the formation of 3D widespread γH2AX foci after high LET carbon-ion irradiation. The large γH2AX foci in G2-phase cells encompassed multiple foci of replication protein A (RPA), a marker of DSBs undergoing resection during homologous recombination. Furthermore, we demonstrated by 3D analysis that the distance between two individual RPA foci within γH2AX foci was approximately 700 nm. Together, our findings suggest that high LET heavy-ion particles induce clustered DSB formation on a scale of approximately 1 μm3. These closely localised DSBs are considered to be a risk for the formation of chromosomal rearrangement after heavy-ion irradiation. PMID:29312614

IgE to penicillins with different specificities can be identified by a multiepitope macromolecule: Bihaptenic penicillin structures and IgE specificities.

PubMed

Ariza, A; Barrionuevo, E; Mayorga, C; Montañez, M I; Perez-Inestrosa, E; Ruiz-Sánchez, A; Rodríguez-Guéant, R M; Fernández, T D; Guéant, J L; Torres, M J; Blanca, M

2014-04-01

Quantitation of specific IgE by immunoassay is a recommended in vitro test for the diagnosis of immediate hypersensitivity reactions to betalactams (BLs), particularly when skin test results are negative. IgE antibodies that recognize the common nuclear structure of all BLs or the specific side chain structure can be mainly distinguished by immunoassays. The aim of this study was to develop an immunoassay system to detect IgE antibodies with different specificities. Cellulose discs conjugated with benzylpenicillin (BP), amoxicillin (AX) or both drugs, with poly-l-lysine (PLL) as carrier molecule, were used as solid phases in the radioallergosorbent test (RAST). Direct and inhibition radioimmunoassay studies were made to verify the structures recognized by serum IgE antibodies from penicillin-allergic patients. Our results indicated that the addition of both haptens did not decrease the capacity to capture IgE when serum specific to either BP or AX was used, at least in terms of sensitivity. In addition, the inclusion of two haptens improved significantly the levels of IgE detection in patients who recognized both BP and AX. Therefore, the use of a solid phase with a carrier molecule conjugated with two determinants (AX and BP) is helpful to recognize IgE antibodies against either of these determinants and is useful for screening sera with different specificities. Copyright © 2014 Elsevier B.V. All rights reserved.

Transcriptional alterations of ET-1 axis and DNA damage in lung tissue of a rat obesity model.

PubMed

Del Ry, Silvia; Cabiati, Manuela; Salvadori, Costanza; Guiducci, Letizia; Caselli, Chiara; Prescimone, Tommaso; Facioni, Maria Sole; Azzarà, Alessia; Chiaramonte, Anna; Mazzoni, Stefano; Bruschi, Fabrizio; Giannessi, Daniela; Scarpato, Roberto

2015-03-01

Obesity has been implicated in the development of many cancers. This can lead to genome damage, especially in the form of double-strand break, the presence of which is now easily detected through nuclear phosphorylation of histone H2AX (γ-H2AX) focus assay. Recently, the endothelin (ET) axis has also been shown to have a role in the growth and progression of several tumors, including lung cancer. The aim of this study was to evaluate the ET-1 system transcriptional alterations and γ-H2AX in lung tissue of Zucker rats subdivided into obese (O, n=22) and controls (CO, n=18) rats: under either fasting conditions (CO(fc)-O(fc)) or acute hyperglycemia (CO(AH)-O(AH)). Significantly higher prepro-ET-1 (p=0.05) and ET-converting enzyme (ECE)-2 mRNA expression was observed in O with respect to CO. A significant positive association was observed between prepro-ET-1 and ET-A in the whole rat population (p=0.009) or in the obese group alone (p=0.007). The levels of γ-H2AX in O and in O(AH) rats were significantly higher (p=0.019) than in the corresponding CO and CO(AH) rats (p=0.038). The study shows an inappropriate secretion of ET-1 in O animals with a parallel DNA damage in their lungs, providing novel mechanisms by which ET receptor antagonist may exert organ protection.

POST CLOSURE INSPECTION AND MONITORING REPORT FOR CORRECTIVE ACTION UNIT 110: AREA 3 WMD U-3AX/BL CRATER, NEVADA TEST SITE, NEVADA FOR THE PERIOD JULY 2004 - JUNE 2005

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

BECHTEL NEVADA

2005-08-01

This Post-Closure Inspection and Monitoring report provides the results of inspections and monitoring for Corrective Action Unit (CAU) 110, Area 3 Waste Management Division (WMD) U-3ax/bl Crater. This report includes an analysis and summary of the site inspections, repairs and maintenance, meteorological information, and soil moisture monitoring data obtained at CAU 110, for the annual period July 2004 through June 2005. Site inspections of the cover were performed quarterly to identify any significant changes to the site requiring action. The overall condition of the cover, cover vegetation, perimeter fence, and use restriction warning signs was good. Settling was observed thatmore » exceeded the action level as specified in Section VII.B.7 of the Hazardous Waste Permit Number NEV HW009 (Nevada Division of Environmental Protection, 2000). This permit states that cracks or settling greater than 15 centimeters (cm) (6 inches [in]) deep that extend 1.0 meter (m) (3 feet [ft]) or more on the cover will be evaluated and repaired within 60 days of detection.« less

High performance p-type thermoelectric materials and methods of preparation

NASA Technical Reports Server (NTRS)

Caillat, Thierry (Inventor); Borshchevsky, Alexander (Inventor); Fleurial, Jean-Pierre (Inventor)

2005-01-01

The present invention is embodied in high performance p-type thermoelectric materials having enhanced thermoelectric properties and the methods of preparing such materials. In one aspect of the invention, p-type semiconductors of formula Zn4-xAxSb3-yBy wherein 0?x?4, A is a transition metal, B is a pnicogen, and 0?y?3 are formed for use in manufacturing thermoelectric devices with substantially enhanced operating characteristics and improved efficiency. Two methods of preparing p-type Zn4Sb3 and related alloys of the present invention include a crystal growth method and a powder metallurgy method.

Applications of Multiconductor Transmission Line Theory to the Prediction of Cable Coupling. Volume 6. A Digital Computer Program for Determining Terminal Currents Induced in a Multiconductor Transmission Line by an Incident Electromagnetic Field

DTIC Science & Technology

1978-02-01

115 6.1.3 Comparison of the Two Solutions -------------------- 131 6.2 Example II...the nonuniform field specification option. - -------------- 149 A-I Illustration of common mode and differential mode currents...Ax subsection in Figure 2-2 in the limit as Ax+0 as a set of 2n coupled, complex, ordinary differential equations [1], V(x) + JwLI(x) = Vs(x) (2-1a) l

Stark Interference of Electric and Magnetic Dipole Transitions in the A-X Band of OH.

PubMed

Schewe, H Christian; Zhang, Dongdong; Meijer, Gerard; Field, Robert W; Sartakov, Boris G; Groenenboom, Gerrit C; van der Avoird, Ad; Vanhaecke, Nicolas

2016-04-15

An experimental method is demonstrated that allows determination of the ratio between the electric (E1) and magnetic (M1) transition dipole moments in the A-X band of OH, including their relative sign. Although the transition strengths differ by more than 3 orders of magnitude, the measured M1-to-E1 ratio agrees with the ratio of the ab initio calculated values to within 3%. The relative sign is found to be negative, also in agreement with theory.

On Positive Solutions for the Rational Difference Equation Systems x n+1 = A/x n y n (2), and y n+1 = By n /x n-1 y n-1.

PubMed

Ma, Hui-Li; Feng, Hui

2014-01-01

Our aim in this paper is to investigate the behavior of positive solutions for the following systems of rational difference equations: x n+1 = A/x n y n (2), and y n+1 = By n /x n-1 y n-1, n = 0,1,…, where x -1, x 0, y -1, and y 0 are positive real numbers and A and B are positive constants.

DNA replication stress induces deregulation of the cell cycle events in root meristems of Allium cepa

PubMed Central

Żabka, Aneta; Polit, Justyna Teresa; Maszewski, Janusz

2012-01-01

Background and Aims Prolonged treatment of Allium cepa root meristems with changing concentrations of hydroxyurea (HU) results in either premature chromosome condensation or cell nuclei with an uncommon form of biphasic chromatin organization. The aim of the current study was to assess conditions that compromise cell cycle checkpoints and convert DNA replication stress into an abnormal course of mitosis. Methods Interphase-mitotic (IM) cells showing gradual changes of chromatin condensation were obtained following continuous 72 h treatment of seedlings with 0·75 mm HU (without renewal of the medium). HU-treated root meristems were analysed using histochemical stainings (DNA-DAPI/Feulgen; starch-iodide and DAB staining for H2O2 production), Western blotting [cyclin B-like (CBL) proteins] and immunochemistry (BrdU incorporation, detection of γ-H2AX and H3S10 phosphorylation). Key Results Continuous treatment of onion seedlings with a low concentration of HU results in shorter root meristems, enhanced production of H2O2, γ-phosphorylation of H2AX histones and accumulation of CBL proteins. HU-induced replication stress gives rise to axially elongated cells with half interphase/half mitotic structures (IM-cells) having both decondensed and condensed domains of chromatin. Long-term HU treatment results in cell nuclei resuming S phase with gradients of BrdU labelling. This suggests a polarized distribution of factors needed to re-initiate stalled replication forks. Furthermore, prolonged HU treatment extends both the relative time span and the spatial scale of H3S10 phosphorylation known in plants. Conclusions The minimum cell length and a threshold level of accumulated CBL proteins are both determining factors by which the nucleus attains commitment to induce an asynchronous course of chromosome condensation. Replication stress-induced alterations in an orderly route of the cell cycle events probably reflect a considerable reprogramming of metabolic functions of chromatin combined with gradients of morphological changes spread along the nucleus. PMID:23087128

Bilingual experience and resting-state brain connectivity: Impacts of L2 age of acquisition and social diversity of language use on control networks.

PubMed

Gullifer, Jason W; Chai, Xiaoqian J; Whitford, Veronica; Pivneva, Irina; Baum, Shari; Klein, Denise; Titone, Debra

2018-05-01

We investigated the independent contributions of second language (L2) age of acquisition (AoA) and social diversity of language use on intrinsic brain organization using seed-based resting-state functional connectivity among highly proficient French-English bilinguals. There were two key findings. First, earlier L2 AoA related to greater interhemispheric functional connectivity between homologous frontal brain regions, and to decreased reliance on proactive executive control in an AX-Continuous Performance Task completed outside the scanner. Second, greater diversity in social language use in daily life related to greater connectivity between the anterior cingulate cortex and the putamen bilaterally, and to increased reliance on proactive control in the same task. These findings suggest that early vs. late L2 AoA links to a specialized neural framework for processing two languages that may engage a specific type of executive control (e.g., reactive control). In contrast, higher vs. lower degrees of diversity in social language use link to a broadly distributed set of brain networks implicated in proactive control and context monitoring. Copyright © 2018 Elsevier Ltd. All rights reserved.

Does the reason for discontinuation of a first TNF inhibitor influence the effectiveness of a second TNF inhibitor in axial spondyloarthritis? Results from the Swiss Clinical Quality Management Cohort.

PubMed

Ciurea, Adrian; Exer, Pascale; Weber, Ulrich; Tamborrini, Giorgio; Steininger, Beate; Kissling, Rudolf O; Bernhard, Jürg; Scherer, Almut

2016-03-22

With regard to switching tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA), conflicting results have been reported as to whether the effectiveness of a second TNFi depends on the reason for discontinuation of the first TNFi. Patients with a clinical diagnosis of axSpA starting a second TNFi in the Swiss Clinical Quality Management cohort were included. Effectiveness of treatment at 1 year, as well as drug survival, was compared between subgroups having discontinued the first TNFi because of lack of response, adverse events (AEs), or other reasons. Lack of response was further divided into primary or secondary lack of response (PLR or SLR, respectively), depending on whether the first TNFi was stopped before or after 6 months of treatment. Among 632 patients with axSpA, median survival of a second TNFi was 1.1 years after PLR and 3.8 years after SLR (p = 0.003). At least moderate disease activity as defined by an Ankylosing Spondylitis Disease Activity Score using the erythrocyte sedimentation rate (ASDAS-ESR) <2.1 was achieved after 12 months by 11 %, 39 %, 26 %, and 39 % of patients who discontinued their first TNFi because of PLR, SLR, AEs, and other reasons, respectively (p = 0.01). Only 4 % of patients achieved an ASDAS-ESR inactive disease state after PLR, in comparison to 22 % of those after SLR. Similar results were demonstrated in patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria for axSpA (n = 488): ASDAS-ESR <2.1 was achieved after 12 months by 9 %, 41 %, 29 %, and 39 % of patients who discontinued their first TNFi because of PLR, SLR, AEs, and other reasons, respectively (p = 0.01). The effectiveness of a second TNFi is significantly impaired in patients with axSpA after PLR to a first TNFi compared with SLR.

Nuclear damage in peripheral lymphocytes of obese and overweight Italian children as evaluated by the gamma-H2AX focus assay and micronucleus test.

PubMed

Scarpato, Roberto; Verola, Carmela; Fabiani, Barbara; Bianchi, Vanessa; Saggese, Giuseppe; Federico, Giovanni

2011-02-01

Childhood obesity, often characterized by a chronic low-grade inflammation, has been associated with an increased risk of developing some types of cancer later in life. Nuclear γ-H2AX foci represent the first detectable response of cells to DNA tumorigenesis lesions, such as the double-strand breaks (DSBs). An excess of micronucleated peripheral lymphocytes was found in subjects with cancer or inflammation-based diseases. We set out to investigate the expression of genome damage, from DNA lesions to chromosome mutations (micronuclei), in overweight and obese children. Using the γ-H2AX focus assay and micronucleus (MN) test, we analyzed peripheral lymphocytes from 119 Italian children classified as normal weight (n=38), overweight (n=20), or obese (n=61). Cultures treated with bleomycin (BLM) were also set up for each child in both assays to check functioning of the apparatus that ensures DNA integrity. We measured serum TNF-α, IL-6, and C-reactive protein (CRP) as markers of inflammation. Overweight and obese children had significantly higher levels of H2AX phosphorylation (0.0191±0.0039 and 0.0274±0.0029 γ-H2AXF/n) and increased MN frequencies (2.30±0.25 and 2.45±0.22‰) than normal-weight children (0.0034±0.0006 γ-H2AXF/n, and 0.92±0.12‰ MN), while all subjects responded to BLM induction, irrespective of their weight status. The fold increase of spontaneous MN frequencies in overweight and obese subjects was 2.5 and 2.7, respectively, well below the corresponding increase in the γ-H2AX foci (5.6- and 8.0-fold, respectively). IL-6 and CRP mean values were significantly higher in obese and overweight children than in controls. Here, we demonstrated that peripheral cells of overweight and obese children showed increased levels of DSBs, which were not completely repaired as part of them has been converted into micronuclei. Characterization of childhood obesity inflammation could be implemented using molecular markers of genome damage.

DNA Damage Signaling Is Induced in the Absence of Epstein-Barr Virus (EBV) Lytic DNA Replication and in Response to Expression of ZEBRA.

PubMed

Wang'ondu, Ruth; Teal, Stuart; Park, Richard; Heston, Lee; Delecluse, Henri; Miller, George

2015-01-01

Epstein Barr virus (EBV), like other oncogenic viruses, modulates the activity of cellular DNA damage responses (DDR) during its life cycle. Our aim was to characterize the role of early lytic proteins and viral lytic DNA replication in activation of DNA damage signaling during the EBV lytic cycle. Our data challenge the prevalent hypothesis that activation of DDR pathways during the EBV lytic cycle occurs solely in response to large amounts of exogenous double stranded DNA products generated during lytic viral DNA replication. In immunofluorescence or immunoblot assays, DDR activation markers, specifically phosphorylated ATM (pATM), H2AX (γH2AX), or 53BP1 (p53BP1), were induced in the presence or absence of viral DNA amplification or replication compartments during the EBV lytic cycle. In assays with an ATM inhibitor and DNA damaging reagents in Burkitt lymphoma cell lines, γH2AX induction was necessary for optimal expression of early EBV genes, but not sufficient for lytic reactivation. Studies in lytically reactivated EBV-positive cells in which early EBV proteins, BGLF4, BGLF5, or BALF2, were not expressed showed that these proteins were not necessary for DDR activation during the EBV lytic cycle. Expression of ZEBRA, a viral protein that is necessary for EBV entry into the lytic phase, induced pATM foci and γH2AX independent of other EBV gene products. ZEBRA mutants deficient in DNA binding, Z(R183E) and Z(S186E), did not induce foci of pATM. ZEBRA co-localized with HP1β, a heterochromatin associated protein involved in DNA damage signaling. We propose a model of DDR activation during the EBV lytic cycle in which ZEBRA induces ATM kinase phosphorylation, in a DNA binding dependent manner, to modulate gene expression. ATM and H2AX phosphorylation induced prior to EBV replication may be critical for creating a microenvironment of viral and cellular gene expression that enables lytic cycle progression.

Technology consumption and cognitive control: Contrasting action video game experience with media multitasking.

PubMed

Cardoso-Leite, Pedro; Kludt, Rachel; Vignola, Gianluca; Ma, Wei Ji; Green, C Shawn; Bavelier, Daphne

2016-01-01

Technology has the potential to impact cognition in many ways. Here we contrast two forms of technology usage: (1) media multitasking (i.e., the simultaneous consumption of multiple streams of media, such a texting while watching TV) and (2) playing action video games (a particular subtype of video games). Previous work has outlined an association between high levels of media multitasking and specific deficits in handling distracting information, whereas playing action video games has been associated with enhanced attentional control. Because these two factors are linked with reasonably opposing effects, failing to take them jointly into account may result in inappropriate conclusions as to the impacts of technology use on attention. Across four tasks (AX-continuous performance, N-back, task-switching, and filter tasks), testing different aspects of attention and cognition, we showed that heavy media multitaskers perform worse than light media multitaskers. Contrary to previous reports, though, the performance deficit was not specifically tied to distractors, but was instead more global in nature. Interestingly, participants with intermediate levels of media multitasking sometimes performed better than both light and heavy media multitaskers, suggesting that the effects of increasing media multitasking are not monotonic. Action video game players, as expected, outperformed non-video-game players on all tasks. However, surprisingly, this was true only for participants with intermediate levels of media multitasking, suggesting that playing action video games does not protect against the deleterious effect of heavy media multitasking. Taken together, these findings show that media consumption can have complex and counterintuitive effects on attentional control.

Efficacy and safety of etanercept in patients from Latin America, Central Europe and Asia with early non-radiographic axial spondyloarthritis.

PubMed

Wei, James Cheng-Chung; Tsai, Wen-Chan; Citera, Gustavo; Kotak, Sameer; Llamado, Lyndon

2016-11-11

To evaluate etanercept in patients from Latin America, Central/Eastern Europe, and Asia with non-radiographic axial spondyloarthritis (nr-axSpA). A subset analysis was performed on nr-axSpA patients from Argentina, Colombia, the Czech Republic, Hungary, Russia and Taiwan who were enrolled in EMBARK (NCT01258738). Patients received either etanercept 50 mg or placebo once weekly. The primary endpoint was proportion of patients achieving 40% improvement from baseline based on Assessment of SpondyloArthritis International Society (ASAS) criteria. Secondary endpoints included other efficacy assessments, health-related quality of life (HRQoL) and safety. Of the 117 patients in this subset, 59 were treated with etanercept and 58 received placebo. At week 12, numerically greater improvements from baseline were observed for all efficacy endpoints in etanercept-treated patients compared with those receiving placebo. Statistically significant differences between the two treatment groups were observed for proportion of patients achieving ASAS40 (P = 0.0413, at week 8), ASAS5/6 (P = 0.0126), Ankylosing Spondylitis Disease Activity Score - C-reactive protein (CRP) inactive disease (P = 0.0093), Spondyloarthritis Research Consortium of Canada magnetic resonance imaging of sacroiliac joint scores (P = 0.0014), high-sensitivity CRP (P=0.032), and erythrocyte sedimentation rate (P = 0.0082). Statistically significant improvements in the etanercept-treated group compared with placebo group were observed for nocturnal back pain (P = 0.040), total back pain (P = 0.025), physician global assessment of disease (P = 0.023), and Work Productivity and Activity Impairment Questionnaire percent impairment while working (P = 0.047). Adverse events were similar between the two treatment groups. In this subset of patients with nr-axSpA from Latin America, Central/Eastern Europe, and Asia, treatment with etanercept, compared with placebo, resulted in improved disease symptoms and patient HRQoL. Etanercept was well tolerated. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

High-Pressure Behavior of Difluorides: The Case of SrF2

NASA Astrophysics Data System (ADS)

Swadba, K. E.; Stan, C. V.; Dutta, R.; Prakapenka, V.; Duffy, T. S.

2016-12-01

The high-pressure behavior of compounds in the AX2 family has attracted much attention due to their extensive polymorphism, highly coordinated structures, and diverse transformation pathways. The canonical transformation sequence for alkaline earth difluorides is from the fluorite-type structure (8 coordinated) to cotunnite (9 coordinated) to Ni2In (11 coordinated). Lead Fluoride, on the other hand, undergoes an unusual isosymmetric transition from cotunnite to a Co2Si-type structure (10 coordinated) at high pressures, during which it exhibits highly anisotropic lattice parameter trends (Haines et al, 1998; Stan et al 2016). Sr has a similar ionic radius as Pb, and is thus a good candidate for further exploring the compressional anisotropy in alkaline earth fluorides. In this study, we report a detailed examination of the compressional behavior of SrF2 to identify whether an intermediate phase occurs in this system prior to transformation to the Ni2In structure. Raman spectroscopy and x-ray diffraction experiments, performed at Princeton University and the Advanced Photon Source GSECARS beamline, respectively, were carried out on SrF2 up to 63 GPa using a diamond anvil cell. From Raman spectroscopy, we observed evidence for a high-pressure phase transition between 38.9 and 51.0 GPa. The x-ray diffraction data in this region show evidence for highly anisotropic compression, most notably a strong negative compressibility in the b direction, in the pressure region from 45.2 to 51.6 GPa. Comparison of our data with lattice parameter systematics for AX2 phases indicates that our results are consistent with the formation of the Co2Si phase in this region, along with a sluggish transformation to the Ni2In-type structure. Our findings contribute to a broader understanding of AX2 compounds and their phase transition pathways.

Comparing the fermentation performance of Escherichia coli KO11, Saccharomyces cerevisiae 424A(LNH-ST) and Zymomonas mobilis AX101 for cellulosic ethanol production

PubMed Central

2010-01-01

Background Fermentations using Escherichia coli KO11, Saccharomyces cerevisiae 424A(LNH-ST), and Zymomonas mobilis AX101 are compared side-by-side on corn steep liquor (CSL) media and the water extract and enzymatic hydrolysate from ammonia fiber expansion (AFEX)-pretreated corn stover. Results The three ethanologens are able produce ethanol from a CSL-supplemented co-fermentation at a metabolic yield, final concentration and rate greater than 0.42 g/g consumed sugars, 40 g/L and 0.7 g/L/h (0-48 h), respectively. Xylose-only fermentation of the tested ethanologenic bacteria are five to eight times faster than 424A(LNH-ST) in the CSL fermentation. All tested strains grow and co-ferment sugars at 15% w/v solids loading equivalent of ammonia fiber explosion (AFEX)-pretreated corn stover water extract. However, both KO11 and 424A(LNH-ST) exhibit higher growth robustness than AX101. In 18% w/w solids loading lignocellulosic hydrolysate from AFEX pretreatment, complete glucose fermentations can be achieved at a rate greater than 0.77 g/L/h. In contrast to results from fermentation in CSL, S. cerevisiae 424A(LNH-ST) consumed xylose at the greatest extent and rate in the hydrolysate compared to the bacteria tested. Conclusions Our results confirm that glucose fermentations among the tested strains are effective even at high solids loading (18% by weight). However, xylose consumption in the lignocellulosic hydrolysate is the major bottleneck affecting overall yield, titer or rate of the process. In comparison, Saccharomyces cerevisiae 424A(LNH-ST) is the most relevant strains for industrial production for its ability to ferment both glucose and xylose from undetoxified and unsupplemented hydrolysate from AFEX-pretreated corn stover at high yield. PMID:20507563

Adenovirus vector-mediated ex vivo gene transfer of brain-derived neurotrophic factor to bone marrow stromal cells promotes axonal regeneration after transplantation in completely transected adult rat spinal cord

PubMed Central

Kamada, Takahito; Hashimoto, Masayuki; Murakami, Masazumi; Shirasawa, Hiroshi; Sakao, Seiichiro; Ino, Hidetoshi; Yoshinaga, Katsunori; Koshizuka, Shuhei; Moriya, Hideshige; Yamazaki, Masashi

2007-01-01

The aim of this study was to evaluate the efficacy in adult rat completely transected spinal cord of adenovirus vector-mediated brain-derived neurotrophic factor (BDNF) ex vivo gene transfer to bone marrow stromal cells (BMSC). BMSC were infected with adenovirus vectors carrying β-galactosidase (AxCALacZ) or BDNF (AxCABDNF) genes. The T8 segment of spinal cord was removed and replaced by graft containing Matrigel alone (MG group) or Matrigel and BMSC infected by AxCALacZ (BMSC-LacZ group) or AxCABDNF (BMSC-BDNF group). Axons in the graft were evaluated by immunohistochemistry and functional recovery was assessed with BBB locomotor scale. In the BMSC-BDNF group, the number of fibers positive for growth associated protein-43, tyrosine hydroxylase, and calcitonin gene-related peptide was significantly larger than numbers found for the MG and BMSC-LacZ groups. Rats from BMSC-BDNF and BMSC-LacZ groups showed significant recovery of hind limb function compared with MG rats; however, there was no significant difference between groups in degree of functional recovery. These findings demonstrate that adenovirus vector-mediated ex vivo gene transfer of BDNF enhances the capacity of BMSC to promote axonal regeneration in this completely transected spinal cord model; however, BDNF failed to enhance hind limb functional recovery. Further investigation is needed to establish an optimal combination of cell therapy and neurotrophin gene transfer for cases of spinal cord injury. PMID:17885772

Implication of fermentable carbohydrates targeting the gut microbiota on conjugated linoleic acid production in high-fat-fed mice.

PubMed

Druart, Céline; Neyrinck, Audrey M; Dewulf, Evelyne M; De Backer, Fabienne C; Possemiers, Sam; Van de Wiele, Tom; Moens, Frédéric; De Vuyst, Luc; Cani, Patrice D; Larondelle, Yvan; Delzenne, Nathalie M

2013-09-28

In vitro experiments have shown that isolated human gut bacteria are able to metabolise PUFA into conjugated PUFA like conjugated linoleic acids (CLA). The hypothesis of the present paper was that high-fat (HF) diet feeding and supplementation with fermentable carbohydrates that have prebiotic properties modulate the in vivo production of CLA by the mouse gut microbiota. Mice were treated for 4 weeks as follows: control (CT) groups were fed a standard diet; HF groups were fed a HF diet rich in linoleic acid (18 : 2n-6); the third groups were fed with the HF diet supplemented with either inulin-type fructans (HF-ITF) or arabinoxylans (HF-Ax). HF diet feeding increased rumenic acid (cis-9,trans-11-18 : 2 CLA) content both in the caecal and liver tissues compared with the CT groups. ITF supplementation had no major effect compared with the HF diet whereas Ax supplementation increased further rumenic acid (cis-9,trans-11-18 : 2 CLA) in the caecal tissue. These differences between both prebiotics may be linked to the high fat-binding capacity of Ax that provides more substrates for bacterial metabolism and to differential modulation of the gut microbiota (specific increase in Roseburia spp. in HF-Ax v. HF). In conclusion, these experiments supply the proof of concept that the mouse gut microbiota produces CLA in vivo, with consequences on the level of CLA in the caecal and liver tissues. We postulate that the CLA-producing bacteria could be a mediator to consider in the metabolic effects of both HF diet feeding and prebiotic supplementation.

Significant Suppression of CT Radiation-Induced DNA Damage in Normal Human Cells by the PrC-210 Radioprotector.

PubMed

Jermusek, Frank; Benedict, Chelsea; Dreischmeier, Emma; Brand, Michael; Uder, Michael; Jeffery, Justin J; Ranallo, Frank N; Fahl, William E

2018-05-21

While computed tomography (CT) is now commonly used and considered to be clinically valuable, significant DNA double-strand breaks (γ-H2AX foci) in white blood cells from adult and pediatric CT patients have been frequently reported. In this study to determine whether γ-H2AX foci and X-ray-induced naked DNA damage are suppressed by administration of the PrC-210 radioprotector, human blood samples were irradiated in a CT scanner at 50-150 mGy with or without PrC-210, and γ-H2AX foci were scored. X-ray-induced naked DNA damage was also studied, and the DNA protective efficacy of PrC-210 was compared against 12 other common "antioxidants." PrC-210 reduced CT radiation-induced γ-H2AX foci in white blood cells to near background ( P < 0.0001) at radiation doses of 50-150 mGy. PrC-210 was most effective among the 13 "antioxidants" in reducing naked DNA X-ray damage, and its addition at 30 s before an • OH pulse reduced to background the • OH insult that otherwise induced >95% DNA damage. A systemic PrC-210 dose known to confer 100% survival in irradiated mice had no discernible effect on micro-CT image signal-to-noise ratio and CT image integrity. PrC-210 suppressed DNA damage to background or near background in each of these assay systems, thus supporting its development as a radioprotector for humans in multiple radiation exposure settings.

The bonding, charge distribution, spin ordering, optical, and elastic properties of four MAX phases Cr{sub 2}AX (A = Al or Ge, X = C or N): From density functional theory study

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

Li, Neng, E-mail: lineng@umkc.edu; Department of Physics and Astronomy, University of Missouri-Kansas City, Kansas City, Missouri 64110; Mo, Yuxiang

2013-11-14

In this work, we assess a full spectrum of properties (chemical bonding, charge distribution, spin ordering, optical, and elastic properties) of Cr{sub 2}AC (A = Al, Ge) and their hypothetical nitride counterparts Cr{sub 2}AN (A = Al, Ge) based on density functional theory calculations. The calculated total energy values indicate that a variety of spin ordering of these four compounds depending on interlayer-interactions between M-A and M-X within the sublattice, which is supported by bonding analysis. MAX phase materials are discovered to possess exotic magnetic properties which indicates that these materials could serve as promising candidates for novel layered magnetic materials for various electronicmore » and spintronic applications. Further analysis of optical properties for two polarization vectors of Cr{sub 2}AX shows that the reflectivity is high in the visible-ultraviolet region up to ∼15 eV suggesting Cr{sub 2}AX as a promising candidate for use as a coating material. The elastic coefficients (C{sub ij}) and bulk mechanical properties [bulk modulus (K), shear modulus (G), Young's modulus (E), Poisson's ratio (η), and Pugh ratio (G/K)] of these four Cr{sub 2}AX compounds are also calculated and analyzed, which pave the way to predict or design new MAX phases that are less brittle or tougher by having a lower G/K value or higher η.« less

Structural variations and dielectric properties of (Bi1-xL ax ) 2Si O5 (0 ≤x ≤0.1 ): Polycrystallines synthesized by crystallization of Bi-Si-O and Bi-La-Si-O glasses

NASA Astrophysics Data System (ADS)

Taniguchi, Hiroki; Tatewaki, Shingo; Yasui, Shintaro; Fujii, Yasuhiro; Yamaura, Jun-ichi; Terasaki, Ichiro

2018-04-01

This paper focuses on effects of isovalent La substitution on the crystal structure and dielectric properties of ferroelectric B i2Si O5 . Polycrystalline samples of (Bi1-xL ax ) 2Si O5 are synthesized by crystallization of Bi-Si-O and Bi-La-Si-O glasses with a composition range of 0 ≤x ≤0.1 . The crystal structure changes from monoclinic to tetragonal with increasing La-substitution rate x at room temperature. This structural variation stems from the change in orientation of Si O4 tetrahedra that form one-dimensional chains when they are in the ordered configuration, thus suggesting that lone-pair electrons play an important role in sustaining one-dimensional chains of Si O4 tetrahedra. Synchronizing with the disordering of Si O4 chains, ferroelectric phase transition temperature of (Bi1-xL ax ) 2Si O5 sharply decreases as x increases, and ferroelectricity finally vanishes at around x =0.03 . The present results demonstrate that lone-pair electrons of Bi play an important role in the ferroelectricity of B i2Si O5 through propping the ordered structure of one-dimensional Si O4 chains with stereochemical activity. Furthermore, an additional phase transition has been first discovered in the low-temperature region of (Bi1-xL ax ) 2Si O5 with x ≤0.01 , where the ordered one-dimensional Si O4 chains remain.

Comprehensive phenotypic analysis of knockout mice deficient in cyclin G1 and cyclin G2

PubMed Central

Ohno, Shouichi; Ikeda, Jun-ichiro; Naito, Yoko; Okuzaki, Daisuke; Sasakura, Towa; Fukushima, Kohshiro; Nishikawa, Yukihiro; Ota, Kaori; Kato, Yorika; Wang, Mian; Torigata, Kosuke; Kasama, Takashi; Uchihashi, Toshihiro; Miura, Daisaku; Yabuta, Norikazu; Morii, Eiichi; Nojima, Hiroshi

2016-01-01

Cyclin G1 (CycG1) and Cyclin G2 (CycG2) play similar roles during the DNA damage response (DDR), but their detailed roles remain elusive. To investigate their distinct roles, we generated knockout mice deficient in CycG1 (G1KO) or CycG2 (G2KO), as well as double knockout mice (DKO) deficient in both proteins. All knockouts developed normally and were fertile. Generation of mouse embryonic fibroblasts (MEFs) from these mice revealed that G2KO MEFs, but not G1KO or DKO MEFs, were resistant to DNA damage insults caused by camptothecin and ionizing radiation (IR) and underwent cell cycle arrest. CycG2, but not CycG1, co-localized with γH2AX foci in the nucleus after γ-IR, and γH2AX-mediated DNA repair and dephosphorylation of CHK2 were delayed in G2KO MEFs. H2AX associated with CycG1, CycG2, and protein phosphatase 2A (PP2A), suggesting that γH2AX affects the function of PP2A via direct interaction with its B’γ subunit. Furthermore, expression of CycG2, but not CycG1, was abnormal in various cancer cell lines. Kaplan–Meier curves based on TCGA data disclosed that head and neck cancer patients with reduced CycG2 expression have poorer clinical prognoses. Taken together, our data suggest that reduced CycG2 expression could be useful as a novel prognostic marker of cancer. PMID:27982046

Fatigue contributes to work productivity impairment in patients with axial spondyloarthritis: a cross-sectional UK study.

PubMed

Espahbodi, Shima; Bassett, Paul; Cavill, Charlotte; Freeth, Mandy; Hole, John; Sengupta, Raj

2017-01-01

To determine factors associated with absenteeism, presenteeism, work productivity loss (WPL), and daily activity impairment in UK patients with AxSpA using standardised measures. 490 patients with AxSpA completed (1) Work Productivity and Impairment questionnaire (WPAI), providing measures for absenteeism, presenteeism, WPL and daily activity impairment, and (2) BASDAI, BASFI, BASMI, Jenkins Sleep scale, Patient Global Assessment disease activity (PGA), back pain night and anytime, EQ-5D for mobility, self-care, daily activities, pain/discomfort, anxiety/depression, EQ-VAS Health State Today, FACIT fatigue, for health-related disease factors. Multivariate linear and logistic regression determined associations between WPAI measures and health-related factors. 301(61%) patients provided WPAI measurements, 76% were male, 87% HLA-B27+. Mean (SD) WPAI scores for absenteeism were 5.1%(19.2), presenteeism 22%(24.3), WPL 23.2%(25.7), activity impairment 34.8%(27.3). Absenteeism was associated with higher fatigue levels and more likely in patients with nrAxSpA. Presenteeism and WPL were both associated higher fatigue levels, BASDAI, and BASFI respectively. Daily activity impairment was associated with higher fatigue levels, BASFI, PGA, EQ-VAS, and smoking. Work productivity and impairment are associated with fatigue, disease activity, and functional ability in UK patients with AxSpA. The strong association of fatigue with all work measures as well as with daily activity impairment emphasises the need to better understand the impact of fatigue on patients' quality of life. Improving fatigue may help to optimise work status.

Enhanced mobility CsPbI 3 quantum dot arrays for record-efficiency, high-voltage photovoltaic cells

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

Sanehira, Erin M.; Marshall, Ashley R.; Christians, Jeffrey A.

Here, we developed lead halide perovskite quantum dot (QD) films with tuned surface chemistry based on A-site cation halide salt (AX) treatments. QD perovskites offer colloidal synthesis and processing using industrially friendly solvents, which decouples grain growth from film deposition, and at present produce larger open-circuit voltages (V OC's) than thin-film perovskites. CsPbI 3 QDs, with a tunable bandgap between 1.75 and 2.13 eV, are an ideal top cell candidate for all-perovskite multijunction solar cells because of their demonstrated small V OC deficit. We show that charge carrier mobility within perovskite QD films is dictated by the chemical conditions atmore » the QD-QD junctions. The AX treatments provide a method for tuning the coupling between perovskite QDs, which is exploited for improved charge transport for fabricating high-quality QD films and devices. The AX treatments presented here double the film mobility, enabling increased photocurrent, and lead to a record certified QD solar cell efficiency of 13.43%.« less

Myelin changes in Alexander disease.

PubMed

Gómez-Pinedo, U; Duran-Moreno, M; Sirerol-Piquer, S; Matias-Guiu, J

2017-03-22

Alexander disease (AxD) is a type of leukodystrophy. Its pathological basis, along with myelin loss, is the appearance of Rosenthal bodies, which are cytoplasmic inclusions in astrocytes. Mutations in the gene coding for GFAP have been identified as a genetic basis for AxD. However, the mechanism by which these variants produce the disease is not understood. The most widespread hypothesis is that AxD develops when a gain of function mutation causes an increase in GFAP. However, this mechanism does not explain myelin loss, given that experimental models in which GFAP expression is normal or mutated do not exhibit myelin disorders. This review analyses other possibilities that may explain this alteration, such as epigenetic or inflammatory alterations, presence of NG2 (+) - GFAP (+) cells, or post-translational modifications in GFAP that are unrelated to increased expression. The different hypotheses analysed here may explain the myelin alteration affecting these patients, and multiple mechanisms may coexist. These theories raise the possibility of designing therapies based on these mechanisms. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

High resolution absolute absorption cross sections of the B ̃(1)A'-X ̃(1)A' transition of the CH2OO biradical.

PubMed

Foreman, Elizabeth S; Kapnas, Kara M; Jou, YiTien; Kalinowski, Jarosław; Feng, David; Gerber, R Benny; Murray, Craig

2015-12-28

Carbonyl oxides, or Criegee intermediates, are formed from the gas phase ozonolysis of alkenes and play a pivotal role in night-time and urban area atmospheric chemistry. Significant discrepancies exist among measurements of the strong B ̃(1)A'-X ̃(1)A' electronic transition of the simplest Criegee intermediate, CH2OO in the visible/near-UV. We report room temperature spectra of the B ̃(1)A'-X ̃(1)A' electronic absorption band of CH2OO acquired at higher resolution using both single-pass broadband absorption and cavity ring-down spectroscopy. The new absorption spectra confirm the vibrational structure on the red edge of the band that is absent from ionization depletion measurements. The absolute absorption cross sections over the 362-470 nm range are in good agreement with those reported by Ting et al. Broadband absorption spectra recorded over the temperature range of 276-357 K were identical within their mutual uncertainties, confirming that the vibrational structure is not due to hot bands.

XPD-dependent activation of apoptosis in response to triplex-induced DNA damage

PubMed Central

Kaushik Tiwari, Meetu; Rogers, Faye A.

2013-01-01

DNA sequences capable of forming triplexes are prevalent in the human genome and have been found to be intrinsically mutagenic. Consequently, a balance between DNA repair and apoptosis is critical to counteract their effect on genomic integrity. Using triplex-forming oligonucleotides to synthetically create altered helical distortions, we have determined that pro-apoptotic pathways are activated by the formation of triplex structures. Moreover, the TFIIH factor, XPD, occupies a central role in triggering apoptosis in response to triplex-induced DNA strand breaks. Here, we show that triplexes are capable of inducing XPD-independent double strand breaks, which result in the formation of γH2AX foci. XPD was subsequently recruited to the triplex-induced double strand breaks and co-localized with γH2AX at the damage site. Furthermore, phosphorylation of H2AX tyrosine 142 was found to stimulate the signaling pathway of XPD-dependent apoptosis. We suggest that this mechanism may play an active role in minimizing genomic instability induced by naturally occurring noncanonical structures, perhaps protecting against cancer initiation. PMID:23913414

Emergent Stimulus Relations Depend on Stimulus Correlation and Not on Reinforcement Contingencies

PubMed Central

Minster, Sara Tepaeru; Elliffe, Douglas; Muthukumaraswamy, Suresh D

2011-01-01

We aimed to investigate whether novel stimulus relations would emerge from stimulus correlations when those relations explicitly conflicted with reinforced relations. In a symbolic matching-to-sample task using kanji characters as stimuli, we arranged class-specific incorrect comparison stimuli in each of three classes. After presenting either Ax or Cx stimuli as samples, choices of Bx were reinforced and choices of Gx or Hx were not. Tests for symmetry, and combined symmetry and transitivity, showed the emergence of three 3-member (AxBxCx) stimulus classes in 5 of 5 human participants. Subsequent tests for all possible emergent relations between Ax, Bx, Cx and the class-specific incorrect comparisons Gx and Hx showed that these relations emerged for 4 of 5 the participants after extended overtraining of the baseline relations. These emergent relations must have been based on stimulus–stimulus correlations, and were not properties of the trained discriminated operants, because they required control by relations explicitly extinguished during training. This result supports theoretical accounts of emergent relations that emphasize stimulus correlation over operant contingencies. PMID:21547070

Enhanced mobility CsPbI 3 quantum dot arrays for record-efficiency, high-voltage photovoltaic cells

DOE PAGES

Sanehira, Erin M.; Marshall, Ashley R.; Christians, Jeffrey A.; ...

2017-10-27

Here, we developed lead halide perovskite quantum dot (QD) films with tuned surface chemistry based on A-site cation halide salt (AX) treatments. QD perovskites offer colloidal synthesis and processing using industrially friendly solvents, which decouples grain growth from film deposition, and at present produce larger open-circuit voltages (V OC's) than thin-film perovskites. CsPbI 3 QDs, with a tunable bandgap between 1.75 and 2.13 eV, are an ideal top cell candidate for all-perovskite multijunction solar cells because of their demonstrated small V OC deficit. We show that charge carrier mobility within perovskite QD films is dictated by the chemical conditions atmore » the QD-QD junctions. The AX treatments provide a method for tuning the coupling between perovskite QDs, which is exploited for improved charge transport for fabricating high-quality QD films and devices. The AX treatments presented here double the film mobility, enabling increased photocurrent, and lead to a record certified QD solar cell efficiency of 13.43%.« less

The Impact of Social Pressure and Monetary Incentive on Cognitive Control.

PubMed

Ličen, Mina; Hartmann, Frank; Repovš, Grega; Slapničar, Sergeja

2016-01-01

We compare the effects of two prominent organizational control mechanisms-social pressure and monetary incentive-on cognitive control. Cognitive control underlies the human ability to regulate thoughts and actions in the pursuit of behavioral goals. Previous studies show that monetary incentives can contribute to goal-oriented behavior by activating proactive control. There is, however, much less evidence of how social pressure affects cognitive control and task performance. In a within-subject experimental design, we tested 47 subjects performing the AX-CPT task to compare the activation of cognitive control modes under social pressure and monetary incentive beyond mere instructions to perform better. Our results indicate that instructing participants to improve their performance on its own leads to a significant shift from a reactive to a proactive control mode and that both social pressure and monetary incentive further enhance performance.

Influence of Different CAM Strategies on the Fit of Partial Crown Restorations: A Digital Three-dimensional Evaluation.

PubMed

Zimmermann, M; Valcanaia, A; Neiva, G; Mehl, A; Fasbinder, D

2018-04-09

CAM fabrication is an important step within the CAD/CAM process. The internal fit of restorations is influenced by the accuracy of the subtractive CAM procedure. Little is known about how CAM strategies might influence the fit of CAD/CAM fabricated restorations. The aim of this study was to three-dimensionally evaluate the fit of CAD/CAM fabricated zirconia-reinforced lithium silicate ceramic partial crowns fabricated with three different CAM strategies. The null hypothesis was that different CAM strategies did not influence the fitting accuracy of CAD/CAM fabricated zirconia-reinforced lithium silicate ceramic partial crowns. Preparation for a partial crown was performed on a maxillary right first molar on a typodont. A chairside CAD/CAM system with the intraoral scanning device CEREC Omnicam (Dentsply Sirona, York, PA, USA) and the 3+1 axis milling unit CEREC MCXL was used. There were three groups with different CAM strategies: step bur 12 (12), step bur 12S (12S), and two step-mode (12TWO). The zirconia-reinforced lithium silicate ceramic Celtra Duo (Dentsply Sirona) was used as the CAD/CAM material. A new 3D method for evaluating the fit was applied, consisting of the quadrant scan with the intraoral scanning device CEREC Omnicam. The scan of the PVS material adherent to the preparation and the preparation scan were matched, and the difference analysis was performed with special software OraCheck (Cyfex AG, Zurich, Switzerland). Three areas were selected for analysis: margin (MA), axial (AX), and occlusal (OC). Statistical analysis was performed using 80% percentile, one-way ANOVA, and the post hoc Scheffé test with α=0.05. Statistically significant differences were found both within and between the test groups. The aspect axial fit results varied from 90.5 ± 20.1 μm for the two-step milling mode (12TWO_AX) to 122.8 ± 12.2 μm for the milling with step bur 12S (12S_AX). The worst result in all groups was found for the aspect occlusal fit with the highest value for group 12S of 222.8 ± 35.6 μm. Group two-step milling mode (12TWO) performed statistically significantly better from groups 12 and 12S for the occlusal fit ( p<0.05). Deviation patterns were visually analyzed with a color-coded scheme for each restoration. CAM strategy influenced the internal adaptation of zirconia-reinforced lithium silicate partial crowns fabricated with a chairside CAD/CAM system. Sensible selection of specific areas of internal adaptation and fit is an important factor for evaluating the CAM accuracy of CAD/CAM systems.

FSH treatment in infertile males candidate to assisted reproduction improved sperm DNA fragmentation and pregnancy rate.

PubMed

Garolla, Andrea; Ghezzi, Marco; Cosci, Ilaria; Sartini, Barbara; Bottacin, Alberto; Engl, Bruno; Di Nisio, Andrea; Foresta, Carlo

2017-05-01

The purpose of this study is to evaluate whether follicle-stimulating hormone treatment improves sperm DNA parameters and pregnancy outcome in infertile male candidates to in-vitro fertilization.Observational study in 166 infertile male partners of couples undergoing in-vitro fertilization. Eighty-four patients were receiving follicle-stimulating hormone treatment (cases) and 82 refused treatment (controls). Semen parameters, sexual hormones, and sperm nucleus (fluorescence in-situ hybridization, acridine orange, TUNEL, and γH2AX) were evaluated at baseline (T0) and after 3 months (T1), when all subjects underwent assisted reproduction techniques. Statistical analysis was performed by analysis of variance.Compared to baseline, cases showed significant improvements in seminal parameters and DNA fragmentation indexes after follicle-stimulating hormone therapy (all P < 0.05), whereas no changes were observed in controls. Within cases, follicle-stimulating hormone treatment allowed to perform intrauterine insemination in 35 patients with a pregnancy rate of 23.2 %. Intracytoplasmic sperm injection was performed in all controls and in 49 patients from cases, with pregnancy rates of 23.2 and 40.8 %, respectively (P < 0.05). After 3 months (T0 vs. T1) of follicle-stimulating hormone therapy, cases with positive outcome had reduced DNA fragmentation index and lower double strand breaks (P < 0.05 and P < 0.001 vs. negative outcome, respectively).In this observational study, we showed that follicle-stimulating hormone treatment improves sperm DNA fragmentation, which in turn leads to increased pregnancy rates in infertile males undergoing in-vitro fertilization. In particular, double strand breaks (measured with γH2AX test) emerged as the most sensible parameter to follicle-stimulating hormone treatment in predicting reproductive outcome.

Minichromosome maintenance complex component 8 mutations cause primary ovarian insufficiency.

PubMed

Dou, Xiaoyun; Guo, Ting; Li, Guangyu; Zhou, LiGuang; Qin, Yingying; Chen, Zi-Jiang

2016-11-01

To investigate whether mutations in the minichromosome maintenance complex component 8 (MCM8) gene were present in 192 patients with sporadic primary ovarian insufficiency (POI). Retrospective case-control cohort study. University-based reproductive medicine center. A total of 192 patients with sporadic POI and 312 control women with regular menstruation (192 age-matched women and 120 women >45 years old). Sanger sequencing was performed in patients with sporadic POI, and potentially pathogenic variants were confirmed in matched controls. DNA damage was induced by mitomycinC (MMC) treatment, and DNA repair capacity was evaluated by histone H2AX phosphorylation level. Sanger sequencing for MCM8 was performed in 192 patients with sporadic POI, and functional experiments were performed to explore the deleterious effects of mutations identified. Two novel missense variants in MCM8, c. A950T (p. H317L), and c. A1802G (p. H601R), were identified in two patients with POI but absent in 312 controls (the upper 90% confidence limit for the proportion 2/192 is 2.24%). The HeLa cells overexpressing mutant p. H317L and p. H601R showed higher sensitivity to MMC compared with wild type. Furthermore, mutant p. H317L showed decreased repair capacity after MMC treatment with much more histone H2AX phosphorylation remaining after 2 hours of recovery. Our result suggests novel mutations p. H317L and p. H601R in the MCM8 gene are potentially causative for POI by dysfunctional DNA repair. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Blood flow patterns during incremental and steady-state aerobic exercise.

PubMed

Coovert, Daniel; Evans, LeVisa D; Jarrett, Steven; Lima, Carla; Lima, Natalia; Gurovich, Alvaro N

2017-05-30

Endothelial shear stress (ESS) is a physiological stimulus for vascular homeostasis, highly dependent on blood flow patterns. Exercise-induced ESS might be beneficial on vascular health. However, it is unclear what type of ESS aerobic exercise (AX) produces. The aims of this study are to characterize exercise-induced blood flow patterns during incremental and steady-state AX. We expect blood flow pattern during exercise will be intensity-dependent and bidirectional. Six college-aged students (2 males and 4 females) were recruited to perform 2 exercise tests on cycleergometer. First, an 8-12-min incremental test (Test 1) where oxygen uptake (VO2), heart rate (HR), blood pressure (BP), and blood lactate (La) were measured at rest and after each 2-min step. Then, at least 48-hr. after the first test, a 3-step steady state exercise test (Test 2) was performed measuring VO2, HR, BP, and La. The three steps were performed at the following exercise intensities according to La: 0-2 mmol/L, 2-4 mmol/L, and 4-6 mmol/L. During both tests, blood flow patterns were determined by high-definition ultrasound and Doppler on the brachial artery. These measurements allowed to determine blood flow velocities and directions during exercise. On Test 1 VO2, HR, BP, La, and antegrade blood flow velocity significantly increased in an intensity-dependent manner (repeated measures ANOVA, p<0.05). Retrograde blood flow velocity did not significantly change during Test 1. On Test 2 all the previous variables significantly increased in an intensity-dependent manner (repeated measures ANOVA, p<0.05). These results support the hypothesis that exercise induced ESS might be increased in an intensity-dependent way and blood flow patterns during incremental and steady-state exercises include both antegrade and retrograde blood flows.

Full-Wave Based Validation of Stripline Field Applicator For Low Frequency Material Measurements

DTIC Science & Technology

2009-03-01

16 3.3.1 Principal Solution. . . . . . . . . . . . . . . . . 17 3.3.2 Reflected Solution. . . . . . . . . . . . . . . . . 22 3.4 Applying...potential) [ 17 ]. The vector potential BCs are found to be Ax(x, y = ±h, z) = 0 ∀ x, z (3.2) ∂Ay(x, y = ±h, z) ∂y = 0 ∀ x, z (3.3) Az(x, y = ±h, z...solution at y = ±h, an inverse Fourier transform must be performed on the principal contribution 17 ηre ηim x x η-plane −jp jp Figure 3.2

Fracture Characteristics of Structural Steels and Weldments

DTIC Science & Technology

1975-11-01

CARACTERISTICS 0F.$ýTRUCTURAL TEL/ - "AD E NTSA .INAL 1 A7 sk S. CONTRACT OR GRANT NUMBER(&) Y.2G. im 9. PERFORMING ORGANIZATION NAME AND ADDRESS -017...36, T- 1,and HY-Y130 Steel and AX. Il 30 15 I Tensile F~racture Surface of A-36 Steel, 12x 31 16 Dimple Rupture in A-6Sel 0X 31 17 Plastic ...sites and the relative plasticity of thle The objective of this study was to use a scanning metal. If many fracture icleation sites initiate mticro

Solution of the symmetric eigenproblem AX=lambda BX by delayed division

NASA Technical Reports Server (NTRS)

Thurston, G. A.; Bains, N. J. C.

1986-01-01

Delayed division is an iterative method for solving the linear eigenvalue problem AX = lambda BX for a limited number of small eigenvalues and their corresponding eigenvectors. The distinctive feature of the method is the reduction of the problem to an approximate triangular form by systematically dropping quadratic terms in the eigenvalue lambda. The report describes the pivoting strategy in the reduction and the method for preserving symmetry in submatrices at each reduction step. Along with the approximate triangular reduction, the report extends some techniques used in the method of inverse subspace iteration. Examples are included for problems of varying complexity.

Functional Analysis of Variants of Unknown Significance in BRCA1 and BRCA2 Using Complementation of a Synthetic Lethal Interaction with PARP Inhibition

DTIC Science & Technology

2014-12-01

general population3-5. A pathogenic mutation in BRCA1 or BRCA2 is an important genetic biomarker for a high ovarian cancer risk in breast cancer patients...doxycycline induces cytological signs of synthetic lethality with Parp inhibitor by RAD51 and RH2AX focus formation. REPORTABLE OUTCOMES None RH2AX... genetics . Mar 2001;68(3):700-710. 3. Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. Journal of clinical oncology : official journal of

Convection Schemes for Use with Curvilinear Coordinate Systems - A Survey.

DTIC Science & Technology

1984-06-01

k ’’j )-,"’, . - It. CONTROLLING OFFICE NAME AND ADDRESS IS. REPORT DATE DEPARTMENT OF THE AR1NY June 1984 US Army Corps of...1 034.0) V - - E(34.d) Now by Taylor series expansion on a uniform grid, f - f ( k ) (Ax) k +1k!O i k ! (5 where the superscript ( k ) indicates the k -tb...derivative. With the derivative operator defined as Df - fx. Eq. (35) can be written k f.- k k fEf ("x) Dk kj- (Ax) k J~O k ! k -O 7- ) which yields

Identifying the principal coefficient of parabolic equations with non-divergent form

NASA Astrophysics Data System (ADS)

Jiang, L. S.; Bian, B. J.

2005-01-01

We deal with an inverse problem of determining a coefficient a(x, t) of principal part for second order parabolic equations with non-divergent form when the solution is known. Such a problem has important applications in a large fields of applied science. We propose a well-posed approximate algorithm to identify the coefficient. The existence, uniqueness and stability of such solutions a(x, t) are proved. A necessary condition which is a couple system of a parabolic equation and a parabolic variational inequality is deduced. Our numerical simulations show that the coefficient is recovered very well.

Symposium on Turbulent Shear Flows (8th) Held in Munich, Germany on 9-11 September 1991. Volume 2. Sessions 19-31, Poster Sessions

DTIC Science & Technology

1991-09-01

FLAMES IN THE ATrR)S1]1 IERE USING A SECOND MOMNT TURBULENCE MODEL Hermilo RAMIREZ -LEON, Claude REY and Jean-Frangois SINI LABORATOIRE DE MECANIQUE DES...65 directly satisfied by an extended version of the C= F , ax6 aX5 artificial compressibility implicit method ( Ramirez -Leon et al,, 1991). 08 2 IR ap...the isotropization-of-production concept. For the compressible fluid case, Ramirez -Leon et al (1990) With regard to Eq (2), the right-hand side of

Development and Clinical Evaluation of a Recombinant-Antigen-Based Cytomegalovirus Immunoglobulin M Automated Immunoassay Using the Abbott AxSYM Analyzer

PubMed Central

Maine, G. T.; Stricker, R.; Schuler, M.; Spesard, J.; Brojanac, S.; Iriarte, B.; Herwig, K.; Gramins, T.; Combs, B.; Wise, J.; Simmons, H.; Gram, T.; Lonze, J.; Ruzicki, D.; Byrne, B.; Clifton, J. D.; Chovan, L. E.; Wachta, D.; Holas, C.; Wang, D.; Wilson, T.; Tomazic-Allen, S.; Clements, M. A.; Wright, G. L.; Lazzarotto, T.; Ripalti, A.; Landini, M. P.

2000-01-01

A new microparticle enzyme immunoassay (MEIA), the Cytomegalovirus (CMV) Immunoglobulin M (IgM) test, was developed on the Abbott AxSYM analyzer. This test uses recombinant CMV antigens derived from portions of four structural and nonstructural proteins of CMV: pUL32 (pp150), pUL44 (pp52), pUL83 (pp65), and pUL80a (pp38). A total of 1,608 specimens from random volunteer blood donors (n = 300), pregnant women (n = 1,118), transplant recipients (n = 6), and patients with various clinical conditions and disease states (n = 184) were tested during development and evaluation of this new assay. In a preliminary clinical evaluation we tested specimens collected prospectively from pregnant women (n = 799) and selected CMV IgM-positive archived specimens from pregnant women (n = 39). The results from the new CMV IgM immunoassay were compared to the results of a consensus interpretation of the results obtained with three commercial CMV IgM immunoassays. The results for specimens with discordant results were resolved by a CMV IgM immunoblot assay. The relative sensitivity, specificity, and agreement for the AxSYM CMV IgM assay were 94.29, 96.28, and 96.19%, respectively, and the resolved sensitivity, specificity, and agreement were 95.83, 97.47, and 97.37%, respectively. We also tested serial specimens from women who experienced seroconversion or a recent CMV infection during gestation (n = 17) and potentially cross-reactive specimens negative for CMV IgM antibody by the consensus tests (n = 184). The AxSYM CMV IgM assay was very sensitive for the detection of CMV IgM during primary CMV infection, as shown by the detection of CMV IgM at the same time as or just prior to the detection of CMV IgG. Specimens from individuals with lupus (n = 16) or parvovirus B19 infection (n = 6) or specimens containing hyper IgM (n = 9), hyper IgG (n = 8), or rheumatoid factor (n = 55) did not cross-react with the AxSYM assay. One specimen each from individuals infected with Epstein-Barr virus (n = 26), measles virus (n = 10), herpes simplex virus (n = 12), or varicella-zoster virus (n = 13) infection, one specimen from an influenza vaccinee (n = 14), and one specimen containing antinuclear antibody cross-reacted with the assay. The overall rate of cross-reactivity of the specimens with the assay was 3.3% (6 of 184). The AxSYM CMV IgM assay is a sensitive and specific assay for the detection of CMV-specific IgM. PMID:10747129

Severe bone marrow edema on sacroiliac joint MRI increases the risk of low BMD in patients with axial spondyloarthritis.

PubMed

Kim, Ha Neul; Jung, Joon-Yong; Hong, Yeon Sik; Park, Sung-Hwan; Kang, Kwi Young

2016-03-02

To determine the association between inflammatory and structural lesions on sacroiliac joint (SIJ) MRI and BMD and to identify risk factors for low BMD in patients with axial spondyloarthritis (axSpA). Seventy-six patients who fulfilled the ASAS axSpA criteria were enrolled. All underwent SIJ MRI and BMD measurement at the lumbar spine, femoral neck, and total hip. Inflammatory and structural lesions on SIJ MRI were scored. Laboratory tests and assessment of radiographic and disease activity were performed at the time of MRI. The association between SIJ MRI findings and BMD was evaluated. Among the 76 patients, 14 (18%) had low BMD. Patients with low BMD showed significantly higher bone marrow edema (BME) and deep BME scores on MRI than those with normal BMD (p < 0.047 and 0.007, respectively). Inflammatory lesions on SIJ MRI correlated with BMD at the femoral neck and total hip. Multivariate analysis identified the presence of deep BME on SIJ MRI, increased CRP, and sacroiliitis on X-ray as risk factors for low BMD (OR = 5.6, 14.6, and 2.5, respectively). The presence of deep BME on SIJ MRI, increased CRP levels, and severity of sacroiliitis on X-ray were independent risk factors for low BMD.

X-ray Weekly Monitoring of the Galactic Center Sgr A* with Suzaku

NASA Astrophysics Data System (ADS)

Maeda, Yoshitomo; Nobukawa, Masayoshi; Hayashi, Takayuki; Iizuka, Ryo; Saitoh, Takayuki; Murakami, Hiroshi

A small gas cloud, G2, is on an orbit almost straight into the supermassive blackhole Sgr A* by spring 2014. This event gives us a rare opportunity to test the mass feeding onto the blackhole by a gas. To catch a possible rise of the mass accretion from the cloud, we have been performing the bi-week monitoring of Sgr A* in autumn and spring in the 2013 fiscal year. The key feature of Suzaku is the high-sensitivity wide-band X-ray spectroscopy all in one observatory. It is characterized by a large effective area combined with low background and good energy resolution, in particular a good line spread function in the low-energy range. Since the desired flare events associated with the G2 approach is a transient event, the large effective area is critical and powerful tools to hunt them. The first monitoring in 2013 autumn was successfully made. The X-rays from Sgr A* and its nearby emission were clearly resolved from the bright transient source AX J1745.6-2901. No very large flare from Sgr A*was found during the monitoring. We also may report the X-ray properties of two serendipitous sources, the neutron star binary AX J1745.6-2901 and a magnetar SGR J1745-29.

The possibilities of using individual birth weights as weaning criteria in dairy goat farming

NASA Astrophysics Data System (ADS)

Gökdal, Özdal; Özuǧur, Ali Kemali; Eren, Vadullah; Atay, Okan

2017-04-01

The aim of the study was to evaluate the possibilities of using individual birth weight of kids as weaning criteria in Saanen and Alpine goats under intensive conditions. A total of 24 does and their 40 kids were divided to weaning groups when the kids reached three (X3) or four times (X4) of their individual birth weights. The experiment design was a 2×2 factorial design with two weaning stages (X3 vs X4) and two breeds (S: Saanen and A: Alpine). The averages of weaning age of the SX3, AX3, SX4 and AX4 kids were determined as 42.75, 42.21, 53.15 and 65.81 days, respectively. The weaning groups and the interaction between weaning and breed had significant effects (P<0.001 and P<0.05, respectively) on weaning age of the kids. The average daily weight gain before weaning was different in weaning groups (P<0.001). On the contrary, the growth performances of the kids until breeding age were not different between groups. The milk yield characteristics of dams in groups were not different. The results indicated that birth weights of the kids can be used successfully for weaning criteria in dairy goats under intensive conditions.

NuSTAR + XMM-Newton monitoring of the neutron star transient AX J1745.6-2901

NASA Astrophysics Data System (ADS)

Ponti, G.; Bianchi, S.; Muñoz-Darias, T.; Mori, K.; De, K.; Rau, A.; De Marco, B.; Hailey, C.; Tomsick, J.; Madsen, K. K.; Clavel, M.; Rahoui, F.; Lal, D. V.; Roy, S.; Stern, D.

2018-01-01

AX J1745.6-2901 is a high-inclination (eclipsing) transient neutron star (NS) low-mass X-ray binary showcasing intense ionized Fe K absorption. We present here the analysis of 11 XMM-Newton and 15 NuSTAR new data sets (obtained between 2013 and 2016), therefore tripling the number of observations of AX J1745.6-2901 in outburst. Thanks to simultaneous XMM-Newton and NuSTAR spectra, we greatly improve on the fitting of the X-ray continuum. During the soft state, the emission can be described by a disc blackbody (kT ∼ 1.1-1.2 keV and inner disc radius rDBB ∼ 14 km), plus hot (kT ∼ 2.2-3.0 keV) blackbody radiation with a small emitting radius (rBB ∼ 0.5 - 0.8 km) likely associated with the boundary layer or NS surface, plus a faint Comptonization component. Imprinted on the spectra are clear absorption features created by both neutral and ionized matter. Additionally, positive residuals suggestive of an emission Fe K α disc line and consistent with relativistic ionized reflection are present during the soft state, while such residuals are not significant during the hard state. The hard-state spectra are characterized by a hard (Γ ∼ 1.9-2.1) power law, showing no evidence for a high energy cut-off (kTe > 60-140 keV) and implying a small optical depth (τ < 1.6). The new observations confirm the previously witnessed trend of exhibiting strong Fe K absorption in the soft state that significantly weakens during the hard state. Optical (GROND) and radio (GMRT) observations suggest for AX J1745.6-2901 a standard broad-band spectral energy distribution as typically observed in accreting NSs.

Mapping of new quantitative trait loci for sudden death syndrome and soybean cyst nematode resistance in two soybean populations.

PubMed

Swaminathan, Sivakumar; Abeysekara, Nilwala S; Knight, Joshua M; Liu, Min; Dong, Jia; Hudson, Matthew E; Bhattacharyya, Madan K; Cianzio, Silvia R

2018-05-01

Novel QTL conferring resistance to both the SDS and SCN was detected in two RIL populations. Dual resistant RILs could be used in breeding programs for developing resistant soybean cultivars. Soybean cultivars, susceptible to the fungus Fusarium virguliforme, which causes sudden death syndrome (SDS), and to the soybean cyst nematode (SCN) (Heterodera glycines), suffer yield losses valued over a billion dollars annually. Both pathogens may occur in the same production fields. Planting of cultivars genetically resistant to both pathogens is considered one of the most effective means to control the two pathogens. The objective of the study was to map quantitative trait loci (QTL) underlying SDS and SCN resistances. Two recombinant inbred line (RIL) populations were developed by crossing 'A95-684043', a high-yielding maturity group (MG) II line resistant to SCN, with 'LS94-3207' and 'LS98-0582' of MG IV, resistant to both F. virguliforme and SCN. Two hundred F 7 derived recombinant inbred lines from each population AX19286 (A95-684043 × LS94-3207) and AX19287 (A95-684043 × LS98-0582) were screened for resistance to each pathogen under greenhouse conditions. Five hundred and eighty and 371 SNP markers were used for mapping resistance QTL in each population. In AX19286, one novel SCN resistance QTL was mapped to chromosome 8. In AX19287, one novel SDS resistance QTL was mapped to chromosome 17 and one novel SCN resistance QTL was mapped to chromosome 11. Previously identified additional SDS and SCN resistance QTL were also detected in the study. Lines possessing superior resistance to both pathogens were also identified and could be used as germplasm sources for breeding SDS- and SCN-resistant soybean cultivars.

Synchrotron-based imaging of chromium and  γ-H2AX immunostaining in the duodenum following repeated exposure to Cr(VI) in drinking water

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

Thompson, Chad M.; Seiter, Jennifer; Chappell, Mark A.

Current drinking water standards for chromium are for the combined total of both hexavalent and trivalent chromium (Cr(VI) and Cr(III)). However, recent studies have shown that Cr(III) is not carcinogenic to rodents, whereas mice chronically exposed to high levels of Cr(VI) developed duodenal tumors. These findings may suggest the need for environmental standards specific for Cr(VI). Whether the intestinal tumors arose through a mutagenic or non-mutagenic mode of action (MOA) greatly impacts how drinking water standards for Cr(VI) are derived. Herein, X-ray fluorescence (spectro)microscopy (µ-XRF) was used to image the Cr content in the villus and crypt regions of duodenamore » from B6C3F1 mice exposed to 180 mg/l Cr(VI) in drinking water for 13 weeks. DNA damage was also assessed by γ-H2AX immunostaining. Exposure to Cr(VI) induced villus blunting and crypt hyperplasia in the duodenum—the latter evidenced by lengthening of the crypt compartment by ~2-fold with a concomitant 1.5-fold increase in the number of crypt enterocytes. γ-H2AX immunostaining was elevated in villi, but not in the crypt compartment. µ-XRF maps revealed mean Cr levels >30 times higher in duodenal villi than crypt regions; mean Cr levels in crypt regions were only slightly above background signal. Despite the presence of Cr and elevated γ-H2AX immunoreactivity in villi, no aberrant foci indicative of transformation were evident. Lastly, these findings do not support a MOA for intestinal carcinogenesis involving direct Cr-DNA interaction in intestinal stem cells, but rather support a non-mutagenic MOA involving chronic wounding of intestinal villi and crypt cell hyperplasia.« less

The strength of polyaxial locking interfaces of distal radius plates.

PubMed

Hoffmeier, Konrad L; Hofmann, Gunther O; Mückley, Thomas

2009-10-01

Currently available polyaxial locking plates represent the consequent enhancement of fixed-angle, first-generation locking plates. In contrast to fixed-angle locking plates which are sufficiently investigated, the strength of the new polyaxial locking options has not yet been evaluated biomechanically. This study investigates the mechanical strength of single polyaxial interfaces of different volar radius plates. Single screw-plate interfaces of the implants Palmar 2.7 (Königsee Implantate und Instrumente zur Osteosynthese GmbH, Allendorf, Germany), VariAx (Stryker Leibinger GmbH & Co. KG, Freiburg, Germany) und Viper (Integra LifeSciences Corporation, Plainsboro, NJ, USA) were tested by cantilever bending. The strength of 0 degrees, 10 degrees and 20 degrees screw locking angle was obtained during static and dynamic loading. The Palmar 2.7 interfaces showed greater ultimate strength and fatigue strength than the interfaces of the other implants. The strength of the VariAx interfaces was about 60% of Palmar 2.7 in both, static and dynamic loading. No dynamic testing was applied to the Viper plate because of its low ultimate strength. By static loading, an increase in screw locking angle caused a reduction of strength for the Palmar 2.7 and Viper locking interfaces. No influence was observed for the VariAx locking interfaces. During dynamic loading; angulation had no influence on the locking strength of Palmar 2.7. However, reduction of locking strength with increasing screw angulation was observed for VariAx. The strength of the polyaxial locking interfaces differs remarkably between the examined implants. Depending on the implant an increase of the screw locking angle causes a reduction of ultimate or fatigue strength, but not in all cases a significant impact was observed.

Automatic detection of DNA double strand breaks after irradiation using an γH2AX assay.

PubMed

Hohmann, Tim; Kessler, Jacqueline; Grabiec, Urszula; Bache, Matthias; Vordermark, Dyrk; Dehghani, Faramarz

2018-05-01

Radiation therapy belongs to the most common approaches for cancer therapy leading amongst others to DNA damage like double strand breaks (DSB). DSB can be used as a marker for the effect of radiation on cells. For visualization and assessing the extent of DNA damage the γH2AX foci assay is frequently used. The analysis of the γH2AX foci assay remains complicated as the number of γH2AX foci has to be counted. The quantification is mostly done manually, being time consuming and leading to person-dependent variations. Therefore, we present a method to automatically analyze the number of foci inside nuclei, facilitating and quickening the analysis of DSBs with high reliability in fluorescent images. First nuclei were detected in fluorescent images. Afterwards, the nuclei were analyzed independently from each other with a local thresholding algorithm. This approach allowed accounting for different levels of noise and detection of the foci inside the respective nucleus, using Hough transformation searching for circles. The presented algorithm was able to correctly classify most foci in cases of "high" and "average" image quality (sensitivity>0.8) with a low rate of false positive detections (positive predictive value (PPV)>0.98). In cases of "low" image quality the approach had a decreased sensitivity (0.7-0.9), depending on the manual control counter. The PPV remained high (PPV>0.91). Compared to other automatic approaches the presented algorithm had a higher sensitivity and PPV. The used automatic foci detection algorithm was capable of detecting foci with high sensitivity and PPV. Thus it can be used for automatic analysis of images of varying quality.

Telephone interview strategy can be used for screening inflammatory back pain in the community.

PubMed

Solmaz, Dilek; Gunduz, Ozgul; Akar, Servet; Can, Gercek; Birlik, Merih; Akkoc, Yesim; Gerdan, Vedat; Onen, Fatos; Akkoc, Nurullah

2017-01-01

Telephone surveys are less expensive and time-consuming for both interviewers and interviewees, with similar or even higher response rates than face-to-face interviews. In rheumatology, telephone technique has been used in a number of epidemiologic studies. In the present study, we conducted a telephone survey for screening inflammatory back pain (IBP) in the community. One hundred and seventy-two patients with axial spondyloarthritis (axSpA) and 25 patients with chronic mechanical back pain were included. A telephone interview and a face-to-face interview was conducted by the same physician using a standardized questionnaire that elicited information on all the components of IBP addressed in the Calin, Berlin and ASAS (the Assessment of SpondyloArthritis International Society) criteria sets. The telephone survey was repeated by another rheumatologist within the same week to assess the inter-rater agreement. Of 172 patients with axSpA, 114 could be classified as ankylosing spondylitis (AS) according to the modified New York criteria (AS group).The remaining 58 patients had active sacroiliitis on magnetic resonance imaging and they constituted the non-radiographic axSpA group (nr-axSpA group). Calin's criteria showed the highest sensitivity but also the lowest specificity with both interview methods. Calin's criteria showed the best agreement between the interview methods (kappa = 0.60). The results of our study indicate that telephone surveys based on Calin's criteria for IBP has a moderate, almost substantial agreement with face-to-face interviews and can be used as an easily applicable, less expensive and time-saving method in screening subjects for IBP. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Low-dose ionizing irradiation triggers a 53BP1 response to DNA double strand breaks in mouse spermatogonial stem cells.

PubMed

Le, Wei; Qi, Lixin; Li, Jiaxuan; Wu, DengIong; Xu, Jun; Zhang, Jinfu

2016-01-01

The present study aims to examine the effect of low-dose ionizing irradiation on DNA double strand breaks (DSB) in mouse spermatogonial stem cells (SSCs) and reveal the underlying pathways for the DNA repair for DSB in SSCs. Eighteen one-month-old mice were divided into 6 groups and sacrificed separately at 45 minutes, 2 hours, 24 hours, 48 hours, and 72 hours after 0.1Gy X-ray irradiation (mice without receiving ionizing irradiation served as control). After perfusion fixation, testes were removed, sectioned, and followed by staining of γH2AX, 53BP1, Caspase 3, and promyelocytic leukemia zinc-finger (PLZF) for analysis among the different groups. The staining was observed by immunofluorescence visualized by confocal laser scanning. After low-dose irradiation, only 53BP1, but not Caspase3 or γH2AX was upregulated in PLZF positive SSCs within 45 minutes. The expression level of 53BP1 gradually decreased 24 hours after irradiation. Moreover, low-dose irradiation had no effect on the cell number and apoptotic status of SSCs. However other spermatogenic cells highly expressed γH2AX shortly after irradiation which was dramatically reduced following the events of DNA repair. It appears that low-dose ionizing irradiation may cause the DNA DSB of mouse spermatogenic cells. 53BP1, but not γH2AX, is involved in the DNA repair for DSB in SSCs. Our data indicates that 53BP1 plays an important role in the pathophysiological repair of DNA DSB in SSCs. This may open a new avenue to understanding the mechanisms of DNA repair of SSCs and male infertility.

Materials of acoustic analysis: sustained vowel versus sentence.

PubMed

Moon, Kyung Ray; Chung, Sung Min; Park, Hae Sang; Kim, Han Su

2012-09-01

Sustained vowel is a widely used material of acoustic analysis. However, vowel phonation does not sufficiently demonstrate sentence-based real-life phonation, and biases may occur depending on the test subjects intent during pronunciation. The purpose of this study was to investigate the differences between the results of acoustic analysis using each material. An individual prospective study. Two hundred two individuals (87 men and 115 women) with normal findings in videostroboscopy were enrolled. Acoustic analysis was done using the speech pattern element acquisition and display program. Fundamental frequency (Fx), amplitude (Ax), contact quotient (Qx), jitter, and shimmer were measured with sustained vowel-based acoustic analysis. Average fundamental frequency (FxM), average amplitude (AxM), average contact quotient (QxM), Fx perturbation (CFx), and amplitude perturbation (CAx) were measured with sentence-based acoustic analysis. Corresponding data of the two methods were compared with each other. SPSS (Statistical Package for the Social Sciences, Version 12.0; SPSS, Inc., Chicago, IL) software was used for statistical analysis. FxM was higher than Fx in men (Fx, 124.45 Hz; FxM, 133.09 Hz; P=0.000). In women, FxM seemed to be lower than Fx, but the results were not statistically significant (Fx, 210.58 Hz; FxM, 208.34 Hz; P=0.065). There was no statistical significance between Ax and AxM in both the groups. QxM was higher than Qx in men and women. Jitter was lower in men, but CFx was lower in women. Both Shimmer and CAx were higher in men. Sustained vowel phonation could not be a complete substitute for real-time phonation in acoustic analysis. Characteristics of acoustic materials should be considered when choosing the material for acoustic analysis and interpreting the results. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells

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

Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

Phosphoramide mustard (PM), the ovotoxic metabolite of the anti-cancer agent cyclophosphamide (CPA), destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage. A previous study demonstrated that PM induces ovarian DNA damage in rat ovaries. To investigate whether PM induces DNA adduct formation, DNA damage and induction of the DNA repair response, rat spontaneously immortalized granulosa cells (SIGCs) were treated with vehicle control (1% DMSO) or PM (3 or 6 μM) for 24 or 48 h. Cell viability was reduced (P < 0.05) after 48 h of exposure to 3 or 6more » μM PM. The NOR-G-OH DNA adduct was detected after 24 h of 6 μM PM exposure, while the more cytotoxic G-NOR-G DNA adduct was formed after 48 h by exposure to both PM concentrations. Phosphorylated H2AX (γH2AX), a marker of DNA double stranded break occurrence, was also increased by PM exposure, coincident with DNA adduct formation. Additionally, induction of genes (Atm, Parp1, Prkdc, Xrcc6, and Brca1) and proteins (ATM, γH2AX, PARP-1, PRKDC, XRCC6, and BRCA1) involved in DNA repair were observed in both a time- and dose-dependent manner. These data support that PM induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response. - Highlights: • PM forms ovarian DNA adducts. • DNA damage marker γH2AX increased by PM exposure. • PM induces ovarian DNA double strand break repair.« less

Targeting HSP90 dimerization via the C-terminus is effective in imatinib resistant CML and lacks heat shock response.

PubMed

Bhatia, Sanil; Diedrich, Daniela; Frieg, Benedikt; Ahlert, Heinz; Stein, Stefan; Bopp, Bertan; Lang, Franziska; Zang, Tao; Kröger, Tobias; Ernst, Thomas; Kögler, Gesine; Krieg, Andreas; Lüdeke, Steffen; Kunkel, Hana; Rodrigues Moita, Ana J; Kassack, Matthias U; Marquardt, Viktoria; Opitz, Friederike V; Oldenburg, Marina; Remke, Marc; Babor, Florian; Grez, Manuel; Hochhaus, Andreas; Borkhardt, Arndt; Groth, Georg; Nagel-Steger, Luitgard; Jose, Joachim; Kurz, Thomas; Gohlke, Holger; Hansen, Finn K; Hauer, Julia

2018-05-03

Heat shock protein 90 (HSP90) stabilizes many client proteins including BCR-ABL1 oncoprotein. BCR-ABL1 is the hallmark of CML in which treatment-free remission (TFR) is limited with clinical and economic consequences. Thus, there is an urgent need for novel therapeutics, which synergize with current treatment approaches. Several inhibitors targeting the N-terminal domain (NTD) of HSP90 are under investigation; however, side effects such as induction of heat shock response (HSR) and toxicity have so far precluded their FDA approval. We have developed a novel inhibitor (referred to as aminoxyrone) of HSP90 function by targeting HSP90 dimerization via the C-terminal domain (CTD). This was achieved by structure-based molecular design, chemical synthesis, and functional pre-clinical in vitro and in vivo validation using CML cell lines and patient-derived CML cells. Aminoxyrone (AX) is a promising potential candidate, which induces apoptosis in leukemic stem cells (LSCs) fraction (CD34 + CD38 - ) as well as the leukemic bulk (CD34 + CD38 + ) of primary CML and in TKI-resistant cells. Furthermore, BCR-ABL1 oncoprotein and related pro-oncogenic cellular responses are downregulated and targeting HSP90 C-terminus by AX does not induce HSR in vitro and in vivo. We also probed the potential of AX in other therapy refractory leukemia such as BCR-ABL1+ BCP-ALL, FLT3-ITD+ AML and Ph-like BCP-ALL. Therefore, AX is the first peptidometic C-terminal HSP90 inhibitor with the potential to increase TFR in TKI sensitive and refractory CML patients and also offers a novel therapeutic option for patients with other therapy-refractory leukemia, due to its low toxicity profile and lack of HSR. Copyright © 2018 American Society of Hematology.

Synchrotron-Based Imaging of Chromium and γ-H2AX Immunostaining in the Duodenum Following Repeated Exposure to Cr(VI) in Drinking Water

PubMed Central

Thompson, Chad M.; Seiter, Jennifer; Chappell, Mark A.; Tappero, Ryan V.; Proctor, Deborah M.; Suh, Mina; Wolf, Jeffrey C.; Haws, Laurie C.; Vitale, Rock; Mittal, Liz; Kirman, Christopher R.; Hays, Sean M.; Harris, Mark A.

2015-01-01

Current drinking water standards for chromium are for the combined total of both hexavalent and trivalent chromium (Cr(VI) and Cr(III)). However, recent studies have shown that Cr(III) is not carcinogenic to rodents, whereas mice chronically exposed to high levels of Cr(VI) developed duodenal tumors. These findings may suggest the need for environmental standards specific for Cr(VI). Whether the intestinal tumors arose through a mutagenic or non-mutagenic mode of action (MOA) greatly impacts how drinking water standards for Cr(VI) are derived. Herein, X-ray fluorescence (spectro)microscopy (µ-XRF) was used to image the Cr content in the villus and crypt regions of duodena from B6C3F1 mice exposed to 180 mg/l Cr(VI) in drinking water for 13 weeks. DNA damage was also assessed by γ-H2AX immunostaining. Exposure to Cr(VI) induced villus blunting and crypt hyperplasia in the duodenum—the latter evidenced by lengthening of the crypt compartment by ∼2-fold with a concomitant 1.5-fold increase in the number of crypt enterocytes. γ-H2AX immunostaining was elevated in villi, but not in the crypt compartment. µ-XRF maps revealed mean Cr levels >30 times higher in duodenal villi than crypt regions; mean Cr levels in crypt regions were only slightly above background signal. Despite the presence of Cr and elevated γ-H2AX immunoreactivity in villi, no aberrant foci indicative of transformation were evident. These findings do not support a MOA for intestinal carcinogenesis involving direct Cr-DNA interaction in intestinal stem cells, but rather support a non-mutagenic MOA involving chronic wounding of intestinal villi and crypt cell hyperplasia. PMID:25352572

Work productivity is associated with disease activity and functional ability in Italian patients with early axial spondyloarthritis: an observational study from the SPACE cohort.

PubMed

de Hooge, Manouk; Ramonda, Roberta; Lorenzin, Mariagrazia; Frallonardo, Paola; Punzi, Leonardo; Ortolan, Augusta; Doria, Andrea

2016-11-16

Spondyloarthritis often affects young people, typically in their working years. The aim of our study was to investigate work productivity and its relationship with disease activity and physical functioning in Italian patients with axial spondyloarthritis (axSpA) with chronic back pain (CBP) for ≥3 months and ≤2 years, and onset  < 45 years of age. Baseline absenteeism, presenteeism, work productivity loss (assessed by the Work Productivity and Activity Impairment questionnaire (WPAI)), and disease activity (assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)/Ankylosing Spondylitis Disease Activity Score (ASDAS)) and functional ability (assessed by the Bath Ankylosing Spondylitis Disease Functional Index (BASFI)) of patients with axSpA (rheumatologist's diagnosis) included in the Italian section of the Spondyloarthritis Caught Early (SPACE) cohort were collected. Multivariate linear regression analysis was used to evaluate the associations between work productivity and disease activity/physical functioning. Absenteeism in 51 patients with axSpA was low (8.3 %). A decrease in work productivity was related to an increase in disease activity. Disease activity was strongly correlated with absenteeism (p < 0.01), presenteeism (p < 0.01) and work productivity loss (p < 0.001). In addition, decreased work productivity was related to a decrease in functional ability. Physical functioning was correlated with absenteeism (p < 0.001), presenteeism (p < 0.05) and work productivity loss (p < 0.001). Impairment of work productivity was correlated with disease activity and physical functioning in Italian patients with axSpA with CBP for ≥3 months and ≤2 years, with onset <45 years of age.

Synchrotron-based imaging of chromium and  γ-H2AX immunostaining in the duodenum following repeated exposure to Cr(VI) in drinking water

DOE PAGES

Thompson, Chad M.; Seiter, Jennifer; Chappell, Mark A.; ...

2014-10-28

Current drinking water standards for chromium are for the combined total of both hexavalent and trivalent chromium (Cr(VI) and Cr(III)). However, recent studies have shown that Cr(III) is not carcinogenic to rodents, whereas mice chronically exposed to high levels of Cr(VI) developed duodenal tumors. These findings may suggest the need for environmental standards specific for Cr(VI). Whether the intestinal tumors arose through a mutagenic or non-mutagenic mode of action (MOA) greatly impacts how drinking water standards for Cr(VI) are derived. Herein, X-ray fluorescence (spectro)microscopy (µ-XRF) was used to image the Cr content in the villus and crypt regions of duodenamore » from B6C3F1 mice exposed to 180 mg/l Cr(VI) in drinking water for 13 weeks. DNA damage was also assessed by γ-H2AX immunostaining. Exposure to Cr(VI) induced villus blunting and crypt hyperplasia in the duodenum—the latter evidenced by lengthening of the crypt compartment by ~2-fold with a concomitant 1.5-fold increase in the number of crypt enterocytes. γ-H2AX immunostaining was elevated in villi, but not in the crypt compartment. µ-XRF maps revealed mean Cr levels >30 times higher in duodenal villi than crypt regions; mean Cr levels in crypt regions were only slightly above background signal. Despite the presence of Cr and elevated γ-H2AX immunoreactivity in villi, no aberrant foci indicative of transformation were evident. Lastly, these findings do not support a MOA for intestinal carcinogenesis involving direct Cr-DNA interaction in intestinal stem cells, but rather support a non-mutagenic MOA involving chronic wounding of intestinal villi and crypt cell hyperplasia.« less

Diets high in resistant starch and arabinoxylan modulate digestion processes and SCFA pool size in the large intestine and faecal microbial composition in pigs.

PubMed

Nielsen, Tina S; Lærke, Helle N; Theil, Peter K; Sørensen, Jens F; Saarinen, Markku; Forssten, Sofia; Knudsen, Knud E Bach

2014-12-14

The effects of a high level of dietary fibre (DF) either as arabinoxylan (AX) or resistant starch (RS) on digestion processes, SCFA concentration and pool size in various intestinal segments and on the microbial composition in the faeces were studied in a model experiment with pigs. A total of thirty female pigs (body weight 63.1 (sem 4.4) kg) were fed a low-DF, high-fat Western-style control diet (WSD), an AX-rich diet (AXD) or a RS-rich diet (RSD) for 3 weeks. Diet significantly affected the digestibility of DM, protein, fat, NSP and NSP components, and the arabinose:xylose ratio, as well as the disappearance of NSP and AX in the large intestine. RS was mainly digested in the caecum. AX was digested at a slower rate than RS. The digesta from AXD-fed pigs passed from the ileum to the distal colon more than twice as fast as those from WSD-fed pigs, with those from RSD-fed pigs being intermediate (P< 0.001). AXD feeding resulted in a higher number of Faecalibacterium prausnitzii, Roseburia intestinalis, Blautia coccoides-Eubacterium rectale, Bifidobacterium spp. and Lactobacillus spp. in the faeces sampled at week 3 of the experimental period (P< 0.05). In the caecum, proximal and mid colon, AXD feeding resulted in a 3- to 5-fold higher pool size of butyrate compared with WSD feeding, with the RSD being intermediate (P <0.001). In conclusion, the RSD and AXD differently affected digestion processes compared with the WSD, and the AXD most efficiently shifted the microbial composition towards butyrogenic species in the faeces and increased the large-intestinal butyrate pool size.

Sensitivity recovery for the AX-PET prototype using inter-crystal scattering events

NASA Astrophysics Data System (ADS)

Gillam, John E.; Solevi, Paola; Oliver, Josep F.; Casella, Chiara; Heller, Matthieu; Joram, Christian; Rafecas, Magdalena

2014-08-01

The development of novel detection devices and systems such as the AX-positron emission tomography (PET) demonstrator often introduce or increase the measurement of atypical coincidence events such as inter-crystal scattering (ICS). In more standard systems, ICS events often go undetected and the small measured fraction may be ignored. As the measured quantity of such events in the data increases, so too does the importance of considering them during image reconstruction. Generally, treatment of ICS events will attempt to determine which of the possible candidate lines of response (LoRs) correctly determine the annihilation photon trajectory. However, methods of assessment often have low success rates or are computationally demanding. In this investigation alternative approaches are considered. Experimental data was taken using the AX-PET prototype and a NEMA phantom. Three methods of ICS treatment were assessed—each of which considered all possible candidate LoRs during image reconstruction. Maximum likelihood expectation maximization was used in conjunction with both standard (line-like) and novel (V-like in this investigation) detection responses modeled within the system matrix. The investigation assumed that no information other than interaction locations was available to distinguish between candidates, yet the methods assessed all provided means by which such information could be included. In all cases it was shown that the signal to noise ratio is increased using ICS events. However, only one method, which used full modeling of the ICS response in the system matrix—the V-like model—provided enhancement in all figures of merit assessed in this investigation. Finally, the optimal method of ICS incorporation was demonstrated using data from two small animals measured using the AX-PET demonstrator.

DNA damage response in renal ischemia-reperfusion and ATP-depletion injury of renal tubular cells

PubMed Central

Ma, Zhengwei; Wei, Qingqing; Dong, Guie; Huo, Yuqing; Dong, Zheng

2014-01-01

Renal ischemia-reperfusion leads to acute kidney injury (AKI) that is characterized pathologically by tubular damage and cell death, followed by tubular repair, atrophy and interstitial fibrosis. Recent work suggested the possible presence of DNA damage response (DDR) in AKI. However, the evidence is sketchy and the role and regulation of DDR in ischemic AKI remain elusive. In this study, we demonstrated the induction of phosphorylation of ATM, H2AX, Chk2 and p53 during renal ischemia-reperfusion in mice, suggesting DDR in kidney tissues. DDR was also induced in vitro during the recovery or “reperfusion” of renal proximal tubular cells (RPTCs) after ATP-depletion. DDR in RPTCs was abrogated by supplying glucose to maintain ATP via glycolysis, indicating that the DDR depends on ATP depletion. The DDR was also suppressed by the general caspase inhibitor z-VAD and the overexpression of Bcl-2, supporting a role of apoptosis-associated DNA damage in the DDR. N-acetylcysteine (NAC), an antioxidant, suppressed the phosphorylation of ATM and p53 and, to a less extent, Chk2, but NAC increased the phosphorylation and nuclear foci formation of H2AX. Interestingly, NAC increased apoptosis, which may account for the observed H2AX activation. Ku55933, an ATM inhibitor, blocked ATM phosphorylation and ameliorated the phosphorylation of Chk2 and p53, but it increased H2AX phosphorylation and nuclear foci formation. Ku55933 also increased apoptosis in RPTCs following ATP-depletion. The results suggest that DDR occurs during renal ischemia-reperfusion in vivo and ATP-depletion injury in vitro. The DDR is partially induced by apoptosis and oxidative stress-related DNA damage. ATM, as a sensor in the DDR, may play a cytoprotective role against tubular cell injury and death. PMID:24726884

Co-targeting deoxyribonucleic acid-dependent protein kinase and poly(adenosine diphosphate-ribose) polymerase-1 promotes accelerated senescence of irradiated cancer cells.

PubMed

Azad, Arun; Bukczynska, Patricia; Jackson, Susan; Haupt, Ygal; Haput, Ygal; Cullinane, Carleen; McArthur, Grant A; Solomon, Benjamin

2014-02-01

To examine the effects of combined blockade of DNA-dependent protein kinase (DNA-PK) and poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1) on accelerated senescence in irradiated H460 and A549 non-small cell lung cancer cells. The effects of KU5788 and AG014699 (inhibitors of DNA-PK and PARP-1, respectively) on clonogenic survival, DNA double-strand breaks (DSBs), apoptosis, mitotic catastrophe, and accelerated senescence in irradiated cells were examined in vitro. For in vivo experiments, H460 xenografts established in athymic nude mice were treated with BEZ235 (a DNA-PK, ATM, and phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor) and AG014699 to determine effects on proliferation, DNA DSBs, and accelerated senescence after radiation. Compared with either inhibitor alone, combination treatment with KU57788 and AG014699 reduced postradiation clonogenic survival and significantly increased persistence of Gamma-H2AX (γH2AX) foci in irradiated H460 and A549 cells. Notably, these effects coincided with the induction of accelerated senescence in irradiated cells as reflected by positive β-galactosidase staining, G2-M cell-cycle arrest, enlarged and flattened cellular morphology, increased p21 expression, and senescence-associated cytokine secretion. In irradiated H460 xenografts, concurrent therapy with BEZ235 and AG014699 resulted in sustained Gamma-H2AX (γH2AX) staining and prominent β-galactosidase activity. Combined DNA-PK and PARP-1 blockade increased tumor cell radiosensitivity and enhanced the prosenescent properties of ionizing radiation in vitro and in vivo. These data provide a rationale for further preclinical and clinical testing of this therapeutic combination. Copyright © 2014. Published by Elsevier Inc.

Correlations between radiation-induced double strand breaks, cell division delay, and cyclin-dependent signaling in x-irradiated NIH3T3 fibroblasts

NASA Astrophysics Data System (ADS)

Cariveau, Mickael J.

2005-07-01

Molecular responses to radiation-induced DNA double strand breaks (DSB) are mediated by the phosphorylation of the histone variant H2AX which forms identifiable gamma-H2AX foci at the site of the DSB. This event is thought to be linked with the down-regulation of signaling proteins contributing to the checkpoints regulating cell cycle progression and, vis-a-vis , the induction of cell division delay. However, it is unclear whether this division delay is directly related to the number of DSB (gamma-H2AX foci) sustained by an irradiated cell and, if so, whether this number drives cells into cell cycle delay or apoptosis. For this reason, studies were conducted in the immortalized NIH/3T3 fibroblast cell in order to establish correlations between the temporal appearance of the gamma-H2AX foci (a DSB) and the expression of the cell cycle regulatory proteins, cyclin E, A, B1, and their cyclin kinase inhibitor, p21. Cell cycle kinetics and flow cytometry were used to establish radiation-induced division delay over a dose range of 1--6 Gy where a mitotic delay of 2.65 min/cGy was established. Correlations between the expression of cyclin E, A, B1, p21, and the generation of DSB were established in NIH/3T3 cells exposed to 2 or 4 Gy x-irradiation. The data suggest that the G1/S and S phase delay (cyclin E and cyclin A protein levels) are dependent on the dose of radiation while the G2/M (cyclin B1 protein levels) delay is dependent on the quantity of DSB sustained by the irradiated cell.

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

Azad, Arun, E-mail: arun.azad@bccancer.bc.ca; Department of Pathology, St. Vincent's Hospital, University of Melbourne, Parkville, Victoria; Bukczynska, Patricia

Purpose: To examine the effects of combined blockade of DNA-dependent protein kinase (DNA-PK) and poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1) on accelerated senescence in irradiated H460 and A549 non-small cell lung cancer cells. Methods and Materials: The effects of KU5788 and AG014699 (inhibitors of DNA-PK and PARP-1, respectively) on clonogenic survival, DNA double-strand breaks (DSBs), apoptosis, mitotic catastrophe, and accelerated senescence in irradiated cells were examined in vitro. For in vivo experiments, H460 xenografts established in athymic nude mice were treated with BEZ235 (a DNA-PK, ATM, and phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor) and AG014699 to determine effects on proliferation, DNA DSBs,more » and accelerated senescence after radiation. Results: Compared with either inhibitor alone, combination treatment with KU57788 and AG014699 reduced postradiation clonogenic survival and significantly increased persistence of Gamma-H2AX (γH2AX) foci in irradiated H460 and A549 cells. Notably, these effects coincided with the induction of accelerated senescence in irradiated cells as reflected by positive β-galactosidase staining, G2-M cell-cycle arrest, enlarged and flattened cellular morphology, increased p21 expression, and senescence-associated cytokine secretion. In irradiated H460 xenografts, concurrent therapy with BEZ235 and AG014699 resulted in sustained Gamma-H2AX (γH2AX) staining and prominent β-galactosidase activity. Conclusion: Combined DNA-PK and PARP-1 blockade increased tumor cell radiosensitivity and enhanced the prosenescent properties of ionizing radiation in vitro and in vivo. These data provide a rationale for further preclinical and clinical testing of this therapeutic combination.« less

PROTEIN KINASE C δ IS A THERAPEUTIC TARGET IN MALIGNANT MELANOMA WITH NRAS MUTATION

PubMed Central

Takashima, Asami; English, Brandon; Chen, Zhihong; Cao, Juxiang; Cui, Rutao; Williams, Robert M.; Faller, Douglas V.

2014-01-01

NRAS is the second most frequently mutated gene in melanoma. Previous reports have demonstrated the sensitivity of cancer cell lines carrying KRAS mutations to apoptosis initiated by inhibition of protein kinase C delta (PKCδ). Here, we report that PKCδ inhibition is cytotoxic in melanomas with primary NRAS mutations. Novel small-molecule inhibitors of PKCδ were designed as chimeric hybrids of two naturally-occurring PKCδ inhibitors, staurosporine and rottlerin. The specific hypothesis interrogated and validated is that combining two domains of two naturally-occurring PKCδ inhibitors into a chimeric or hybrid structure retains biochemical and biological activity, and improves PKCδ isozyme selectivity. We have devised a potentially general synthetic protocol to make these chimeric species using Molander trifluorborate coupling chemistry. Inhibition of PKCδ, by siRNA or small molecule inhibitors, suppressed the growth of multiple melanoma cell lines carrying NRAS mutations, mediated via caspase-dependent apoptosis. Following PKCδ inhibition, the stress-responsive JNK pathway was activated, leading to the activation of H2AX. Consistent with recent reports on the apoptotic role of phospho-H2AX, knockdown of H2AX prior to PKCδ inhibition mitigated the induction of caspase-dependent apoptosis. Furthermore, PKCδ inhibition effectively induced cytotoxicity in BRAF-mutant melanoma cell lines that had evolved resistance to a BRAF inhibitor, suggesting the potential clinical application of targeting PKCδ in patients who have relapsed following treatment with BRAF inhibitors. Taken together, the present work demonstrates that inhibition of PKCδ by novel small molecule inhibitors causes caspase-dependent apoptosis mediated via the JNK-H2AX pathway in melanomas with NRAS mutations or BRAF inhibitor-resistance. PMID:24506253

Separation of anionic oligosaccharides by high-performance liquid chromatography

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

Green, E.D.; Baenziger, J.U.

1986-10-01

The authors have developed methods for rapid fractionation of anionic oligosaccharides containing sulfate and/or sialic acid moieties by high-performance liquid chromatography (HPLC). Ion-exchange HPLC on amine-bearing columns (Micropak AX-10 and AX-5) at pH 4.0 is utilized to separate anionic oligosaccharides bearing zero, one, two, three, or four charges, independent of the identity of the anionic moieties (sulfate and/or sialic acid). Ion-exchange HPLC at pH 1.7 allows separation of neutral, mono-, di-, and tetrasialylated, monosulfated, and disulfated oligosaccharides. Oligosaccharides containing three sialic acid residues and those bearing one each of sulfate and sialic acid, however, coelute at pH 1.7. Since themore » latter two oligosaccharide species separate at pH 4.0, analysis at pH 4.0 followed by analysis at pH 1.7 can be utilized to completely fractionate complex mixtures of sulfated and sialylated oligosaccharides. Ion-suppression amine adsorption HPLC has previously been shown to separate anionic oligosaccharides on the basis of net carbohydrate content (size). In this study they demonstrate the utility of ion-suppression amine adsorption HPLC for resolving sialylated oligosaccharide isomers which differ only in the linkages of sialic acid residues (..cap alpha..2,3 vs ..cap alpha..2,6) and/or location of ..cap alpha..2,3- and ..cap alpha..2,6-linked sialic acid moieties on the peripheral branches of oligosaccharides. These two methods can be used in tandem to separate oligosaccharides, both analytically and preparatively, based on their number, types, and linkages of anionic moieties.« less

The Impact of Social Pressure and Monetary Incentive on Cognitive Control

PubMed Central

Ličen, Mina; Hartmann, Frank; Repovš, Grega; Slapničar, Sergeja

2016-01-01

We compare the effects of two prominent organizational control mechanisms—social pressure and monetary incentive—on cognitive control. Cognitive control underlies the human ability to regulate thoughts and actions in the pursuit of behavioral goals. Previous studies show that monetary incentives can contribute to goal-oriented behavior by activating proactive control. There is, however, much less evidence of how social pressure affects cognitive control and task performance. In a within-subject experimental design, we tested 47 subjects performing the AX-CPT task to compare the activation of cognitive control modes under social pressure and monetary incentive beyond mere instructions to perform better. Our results indicate that instructing participants to improve their performance on its own leads to a significant shift from a reactive to a proactive control mode and that both social pressure and monetary incentive further enhance performance. PMID:26903901

An Interface Tracking Algorithm for the Porous Medium Equation.

DTIC Science & Technology

1983-03-01

equation (1.11). N [v n n 2(2) = n . AV k + wk---IY" 2] +l~ x A t K Ax E E 2+ VeTA i;- 2k1 n- o (nr+l) <k-<.(n+l) N [Av] [ n+l <Ax Z m(v ) I~+lIAxAt...RD-R127 685 AN INTERFACE TRACKING ALGORITHM FOR THE POROUS MEDIUM / EQURTION(U) WISCONSIN UNIV-MRDISON MATHEMATICS RESEARCH CENTER E DIBENEDETTO ET...RL. MAR 83 NRC-TSR-249 UNCLASSIFIED DAG29-88-C-8041 F/G 12/1i N E -EEonshhhhI EhhhMhhhhhhhhE mhhhhhhhhhhhhE mhhhhhhhhhhhhI IMhhhhhhhMhhhE

Magnetic properties of the mixed ferro-ferrimagnets composed of Prussian blue analogs with (AxB1 x)yC

NASA Astrophysics Data System (ADS)

Hu, Hongliang; Xin, Zihua; Liu, Weijie

2006-09-01

The phase diagrams of the mixed ferro-ferrimagnets composed of Prussian blue analogs with (AxB1 x)yC, consisting of spins S=1, S=5/2 and S=3/2, are investigated by the use of the effective-field theory with the correlations based on Ising model. The phase diagrams which are related to experimental work of molecule-based ferro-ferrimagnets (NiIIxMnII1 x)1.5[CrIII(CN)6] are obtained. The magnetic properties such as magnetization, the critical temperature, the compensation temperature, internal energy and specific heat are also calculated.

Numerical radius and zero pattern of matrices

NASA Astrophysics Data System (ADS)

Nikiforov, Vladimir

2008-01-01

Let A be an n×n complex matrix and r be the maximum size of its principal submatrices with no off-diagonal zero entries. Suppose A has zero main diagonal and x is a unit n-vector. Then, letting ||A|| be the Frobenius norm of A, we show that2[less-than-or-equals, slant](1-1/2r-1/2n)||A||2. This inequality is tight within an additive term O(rn-2). If the matrix A is Hermitian, then2[less-than-or-equals, slant](1-1/r)||A||2. This inequality is sharp; moreover, it implies the Turán theorem for graphs.

Integrating sequencing batch reactor with bio-electrochemical treatment for augmenting remediation efficiency of complex petrochemical wastewater.

PubMed

Yeruva, Dileep Kumar; Jukuri, Srinivas; Velvizhi, G; Naresh Kumar, A; Swamy, Y V; Venkata Mohan, S

2015-01-01

The present study evaluates the sequential integration of two advanced biological treatment methods viz., sequencing batch reactor (SBR) and bioelectrochemical treatment systems (BET) for the treatment of real-field petrochemical wastewater (PCW). Initially two SBR reactors were operated in aerobic (SBR(Ae)) and anoxic (SBR(Ax)) microenvironments with an organic loading rate (OLR) of 9.68 kg COD/m(3)-day. Relatively, SBR(Ax) showed higher substrate degradation (3.34 kg COD/m(3)-day) compared to SBR(Ae) (2.9 kg COD/m(3)-day). To further improve treatment efficiency, the effluents from SBR process were fed to BET reactors. BET(Ax) depicted higher SDR (1.92 kg COD/m(3)-day) with simultaneous power generation (17.12 mW/m(2)) followed by BET(Ae) (1.80 kg COD/m(3)-day; 14.25 mW/m(2)). Integrating both the processes documented significant improvement in COD removal efficiency due to the flexibility of combining multiple microenvironments sequentially. Results were supported with GC-MS and FTIR, which confirmed the increment in biodegradability of wastewater. Copyright © 2015 Elsevier Ltd. All rights reserved.

Generation of DNA single-strand displacement by compromised nucleotide excision repair

PubMed Central

Godon, Camille; Mourgues, Sophie; Nonnekens, Julie; Mourcet, Amandine; Coin, Fréderic; Vermeulen, Wim; Mari, Pierre-Olivier; Giglia-Mari, Giuseppina

2012-01-01

Nucleotide excision repair (NER) is a precisely coordinated process essential to avoid DNA damage-induced cellular malfunction and mutagenesis. Here, we investigate the mechanistic details and effects of the NER machinery when it is compromised by a pathologically significant mutation in a subunit of the repair/transcription factor TFIIH, namely XPD. In contrast to previous studies, we find that no single- or double-strand DNA breaks are produced at early time points after UV irradiation of cells bearing a specific XPD mutation, despite the presence of a clear histone H2AX phosphorylation (γH2AX) signal in the UV-exposed areas. We show that the observed γH2AX signal can be explained by the presence of longer single-strand gaps possibly generated by strand displacement. Our in vivo measurements also indicate a strongly reduced TFIIH-XPG binding that could promote single-strand displacement at the site of UV lesions. This finding not only highlights the crucial role of XPG's interactions with TFIIH for proper NER, but also sheds new light on how a faulty DNA repair process can induce extreme genomic instability in human patients. PMID:22863773

Search for the OH (X(2)Pi) Meinel band emission in meteors as a tracer of mineral water in comets: detection of N(2)(+) (A-X)

NASA Technical Reports Server (NTRS)

Jenniskens, Peter; Laux, Christophe O.

2004-01-01

We report the discovery of the N(2)(+) A-X Meinel band in the 780-840 nm meteor emission from two Leonid meteoroids that were ejected less than 1000 years ago by comet 55P/Tempel-Tuttle. Our analysis indicates that the N(2)(+) molecule is at least an order of magnitude less abundant than expected, possibly as a result of charge transfer reactions with meteoric metal atoms. This new band was found while searching for rovibrational transitions in the X(2)Pi electronic ground state of OH (the OH Meinel band), a potential tracer of water bound to minerals in cometary matter. The electronic A-X transition of OH has been identified in other Leonid meteors. We did not detect this OH Meinel band, which implies that the excited A state is not populated by thermal excitation but by a mechanism that directly produces OH in low vibrational levels of the excited A(2)Sigma state. Ultraviolet dissociation of atmospheric or meteoric water vapor is such a mechanism, as is the possible combustion of meteoric organics.

A Comparative Study on Alexithymia in Depressive, Somatoform, Anxiety, and Psychotic Disorders among Koreans

PubMed Central

Son, Sung hwa; Jo, Hyunyoung; Rim, Hyo Deog; Kim, Ju Hee; Kim, Hea Won; Bae, Geum Ye

2012-01-01

Objective Little is known about the characteristic differences in alexithymic construct in various psychiatric disorders because of a paucity of direct comparisons between psychiatric disorders. Therefore, this study explored disorder-related differences in alexithymic characteristics among Korean patients diagnosed with four major psychiatric disorders (n=388). Methods Alexithymic tendencies, as measured by the Korean version of the 20-item Toronto Alexithymia Scale (TAS-20K), of patients classified into four groups according to major psychiatric diagnosis were compared. The groups consisted of patients with depressive disorders (DP; n=125), somatoform disorders (SM; n=78), anxiety disorders (AX; n=117), and psychotic disorders (PS; n=68). Results We found that substantial portions of patients in all groups were classified as having alexithymia and no statistical intergroup differences emerged (42.4%, 35.9%, 35.3%, and 33.3% for DP, SM, PS, and AX). However, patients with DP obtained higher scores in factor 2 (difficulties describing feelings) than those with SM or AX, after adjusting for demographic variables. Conclusion These findings suggest that alexithymia might be associated with a higher vulnerability to depressive disorders and factor 2 of TAS-20K could be a discriminating feature of depressive disorders. PMID:23251195

Effect of Brönsted acidic ionic liquid 1-(1-propylsulfonic)-3-methylimidazolium chloride on growth and co-fermentation of glucose, xylose and arabinose by Zymomonas mobilis AX101.

PubMed

Gyamerah, M; Ampaw-Asiedu, M; Mackey, J; Menezes, B; Woldesenbet, S

2018-06-01

The potential of large-scale lignocellulosic biomass hydrolysis to fermentable sugars using ionic liquids has increased interest in this green chemistry route to fermentation for fuel-ethanol production. The ionic liquid 1-(1-propylsulfonic)-3-methylimidazolium chloride compared to other reported ionic liquids has the advantage of hydrolysing lignocellulosic biomass to reducing sugars at catalytic concentrations (≤0·032 mol l -1 ) in a single step. However, effects of this ionic liquid on co-fermentation of glucose, xylose and arabinose to ethanol by recombinant Zymomonas mobilisAX101 has not been studied. Authentic glucose, xylose and arabinose were used to formulate fermentation media at varying catalytic 1-(1-propylsulfonic)-3-methylimidazolium chloride concentrations for batch co-fermentation of the sugars using Z. mobilisAX101. The results showed that at 0·008, 0·016 and 0·032 mol l -1 ionic liquid in the culture medium, cell growth decreased by 10, 27 and 67% respectively compared to the control. Ethanol yields were 62·6, 61·8, 50·5 and 23·1% for the control, 0·008, 0·016 and 0·032 mol l -1 ionic liquid respectively. The results indicate that lignocellulosic biomass hydrolysed using 0·008 mol l -1 of 1-(1-propylsulfonic)-3-methylimidazolium chloride would eliminate an additional separation step and provide a ready to use fermentation substrate. This is the first reported study of the effect of the Brönsted acidic ionic liquid 1-(1-propylsulfonic)-3-methylimidazolium chloride on growth and co-fermentation of glucose, xylose and arabinose by Zymomonas mobilisAX101 in batch culture. Growth on and co-fermentation of the sugars by Z. mobilisAX 101 with no significant inhibition by the ionic liquid at the same catalytic amounts of 0·008 mol l -1 used to hydrolyse lignocellulosic biomass to reducing sugars overcome two major hurdles that adversely affect the process economics of large-scale industrial cellulosic fuel ethanol production; the energy-intensive hydrolysis and ionic liquid separation steps. © 2018 The Society for Applied Microbiology.

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

Heijst, T C F van; Hoekstra, N; Philippens, M E P

Purpose: The Utrecht MRI-linac (MRL) design enables new MR-guided radiotherapy (RT) approaches. This is a feasibility study for a single-fraction high dose (boost) to individual lymph nodes (LNs) in breast-cancer patients, after breast-conserving surgery (BCS) and hypofractionated whole-breast irradiation (WBI) with conventional axillary RT (AxRT). Methods: After written informed consent, 5 breast-cancer patients (cT1-3N0) were enrolled (NL500460.041.14 trial) and underwent 1.5T MRI in supine RT position, after BCS. Axillary levels, based on ESTRO guidelines, and organs-at-risk (OARs) – including lungs, chest wall, plexus and neurovascular bundle (NVB) – were delineated. Pseudo-CT scans (pCTs) were generated by HU bulk-assignment of water,more » lung, and air. With Monaco treatment-planning software (TPS Elekta), VMAT plans were generated for simultaneous WBI and AxRT, prescribing 16×2.66=42.56Gy (V95%>99% V107%<2cc). Two scenarios were considered: AxRT of levels I–II; AxRT of levels I–IV, depending on boost location. Per patient, 4 LNs with varying axillary locations were selected, delineated, and expanded to PTV with 2-mm margin. Using dedicated MRL TPS, accounting for magnetic-field effects, an IMRT 1×8.5Gy boost was simulated for each LN, to achieve a total target dose of 66Gy EQD2 (α/β=3.5Gy). WBI/ART doses and boost doses were added, and evaluated in EQD2. Results: For all scenarios, 1×8.5Gy boosts could be simulated within clinical constraints for a 66Gy total dose, in addition to WBI/AxRT. LN target coverage was excellent (V95%>95%, mean >8.5Gy). Additional dose to OARs was limited. Conclusion: Our study explored the concept of LN boosting using on-line MRI guidance. It is feasible to boost individual axillary LNs – with 2-mm margin – with an additional 1×8.5Gy, in all axillary levels, within clinical constraints. This may lead to more personalized RT approaches for patients with involved LNs and may reduce RT-induced toxicity, or the need for axillary surgery. Other LN boost strategies, including dose escalation, are under investigation.« less

Summary of Two Independent Performance Measurements of the ONR Axial Waterjet 2 (AxWJ-2)

DTIC Science & Technology

2011-03-01

From the shaft centerline to rlR = 0.1, there is a velocity defect caused by the wake of the stator hub. The flow along the stator hub is quick to...centered about the shaft centerline. The inner core rotates opposite in direction to the rotor and radiates out to rlR = 0.15. From there to rlR = 0.40 is...centroid of the inner core, rlR = 0.00. This problem may be traced to the large sensing volume of the RRNMI 3-hole pitot probe or misalignment of the probe

High-Precision Pulse Generator

NASA Technical Reports Server (NTRS)

Katz, Richard; Kleyner, Igor

2011-01-01

A document discusses a pulse generator with subnanosecond resolution implemented with a low-cost field-programmable gate array (FPGA) at low power levels. The method used exploits the fast carry chains of certain FPGAs. Prototypes have been built and tested in both Actel AX and Xilinx Virtex 4 technologies. In-flight calibration or control can be performed by using a similar and related technique as a time interval measurement circuit by measuring a period of the stable oscillator, as the delays through the fast carry chains will vary as a result of manufacturing variances as well as the result of environmental conditions (voltage, aging, temperature, and radiation).

Testing of materials for passive thermal control of space suits

NASA Technical Reports Server (NTRS)

Squire, Bernadette

1988-01-01

An effort is underway to determine the coating material of choice for the AX-5 prototype hard space suit. Samples of 6061 aluminum have been coated with one of 10 selected metal coatings, and subjected to corrosion, abrasion, and thermal testing. Changes in reflectance after exposure are documented. Plated gold exhibited minimal degradation of optical properties. A computer model is used in evaluating coating thermal performance in the EVA environment. The model is verified with an experiment designed to measure the heat transfer characteristics of coated space suit parts in a thermal vacuum chamber. Details of this experiment are presented.

A shoreline fumigation model with wind shear

NASA Astrophysics Data System (ADS)

Zhibian, Li; Zengquan, Yao

A fumigation model has been developed for a plume discharged from an elevated stack in a shoreline environment by introducing different wind directions above and within thermal internal boundary laye:r (TIBL) into a dispersion model. When a continuous point source release occurs above the TIBL pollutants will disperse in the marine stable flow, until the plume intersects the TIBL surface. The fumigation in ithe TIBL is interpreted as occurring from an area source on the imaginary surface of the TIBL. It is assumed that the wind direction varies with height above and below L( x) = Ax2, the height of the TIBL at the distance x. The change of wind direction above and within the TIBL causes the pollutants to change their direction of transport and leads to development of a curved ground level concentration (glc) axis; a decreasing glc along the centreline of the fumigation and a widening pollutant distribution in the transverse direction. Predicted concentration distributions using the wind shear model are compared with observations from an SF 6 tracer experiment near Hangzhou Bay in May-June of 1987. The comparison and an evaluation of the model performance show that the new model is not only more theoretically acceptable than those based on empirical coefficients but also provides concentration distributions which agree well with. SF 6 tracer experiments.

ART-SCIENCE OF THE SPACE AGE: towards a platform for art-science collaborations at ESTEC

NASA Astrophysics Data System (ADS)

Domnitch, E.; Gelfand, D.

2015-10-01

In 2013, in collaboration with ESTEC scientist Bernard Foing and the ArtScience Interfaculty (Royal Academy of the Arts, The Hague), Synergetica Lab (Amsterdam) developed a course, which was repeated in 2015, for bachelor's and master's students aimed at seeding interactions with ESA researchers. The participants created artworks investigating space travel, radio astronomy, microgravity, ecosynthesis as well as extraterrestrial physics and architecture [1] [2]. After their initial presentation at the Royal Academy, these artworks were shown at ESTEC, TodaysArt Festival (The Hague), and TEC ART (Rotterdam). These presentations prompted diverse future collaborations and outreach opportunities, including the European Planetary Science Congress 2014 (Cascais) and the AxS Festival (Los Angeles).

Hydrodynamics at Mouth of Colorado River, Texas, Project. Numerical Model Investigation

DTIC Science & Technology

1992-09-01

in de - tail by Thomas and McAnally (1985). 2. The three basic components of the system are as follows: £. "A Two-Dimensional Model for Free Surface...into smaller subareas, which are called ele - ments. The dependent variables (e.g., water-surface elevations and sediment A2 -iriI r IJ I I I .E 7-1 a...x hi auLa + hh ý- + hu L- + hv - + h x at ax 2y + vx 2 1/ 2 ) + gun 22 + v 2 ]1cos h - 2hwv sin 4 - 0 (Al) 1l.486hl1/6)1 hu L- + hv L -h e+ey ha y at

Low Doses of Gamma-Irradiation Induce an Early Bystander Effect in Zebrafish Cells Which Is Sufficient to Radioprotect Cells

PubMed Central

Pereira, Sandrine; Malard, Véronique; Ravanat, Jean-Luc; Davin, Anne-Hélène; Armengaud, Jean; Foray, Nicolas; Adam-Guillermin, Christelle

2014-01-01

The term “bystander effect” is used to describe an effect in which cells that have not been exposed to radiation are affected by irradiated cells though various intracellular signaling mechanisms. In this study we analyzed the kinetics and mechanisms of bystander effect and radioadaptation in embryonic zebrafish cells (ZF4) exposed to chronic low dose of gamma rays. ZF4 cells were irradiated for 4 hours with total doses of gamma irradiation ranging from 0.01–0.1 Gy. In two experimental conditions, the transfer of irradiated cells or culture medium from irradiated cells results in the occurrence of DNA double strand breaks in non-irradiated cells (assessed by the number of γ-H2AX foci) that are repaired at 24 hours post-irradiation whatever the dose. At low total irradiation doses the bystander effect observed does not affect DNA repair mechanisms in targeted and bystander cells. An increase in global methylation of ZF4 cells was observed in irradiated cells and bystander cells compared to control cells. We observed that pre-irradiated cells which are then irradiated for a second time with the same doses contained significantly less γ-H2AX foci than in 24 h gamma-irradiated control cells. We also showed that bystander cells that have been in contact with the pre-irradiated cells and then irradiated alone present less γ-H2AX foci compared to the control cells. This radioadaptation effect is significantly more pronounced at the highest doses. To determine the factors involved in the early events of the bystander effect, we performed an extensive comparative proteomic study of the ZF4 secretomes upon irradiation. In the experimental conditions assayed here, we showed that the early events of bystander effect are probably not due to the secretion of specific proteins neither the oxidation of these secreted proteins. These results suggest that early bystander effect may be due probably to a combination of multiple factors. PMID:24667817

DNA double-strand breaks in blood lymphocytes induced by two-day 99mTc-MIBI myocardial perfusion scintigraphy.

PubMed

Rief, Matthias; Hartmann, Lisa; Geisel, Dominik; Richter, Felicitas; Brenner, Winfried; Dewey, Marc

2018-07-01

To investigate DNA double-strand breaks (DSBs) in blood lymphocytes induced by two-day 99m Tc-MIBI myocardial perfusion scintigraphy (MPS) using y-H2AX immunofluorescence microscopy and to correlate the results with 99m Tc activity in blood samples. Eleven patients who underwent two-day MPS were included. DSB blood sampling was performed before and 5min, 1h and 24h after the first and second radiotracer injections. 99m Tc activity was measured in each blood sample. For immunofluorescence microscopy, distinct foci representing DSBs were quantified in lymphocytes after staining for the phosphorylated histone variant y-H2AX. The 99m Tc-MIBI activity measured on days one and two was similar (254±25 and 258±27 MBq; p=0.594). Compared with baseline DSB foci (0.09±0.05/cell), a significant increase was found at 5min (0.19±0.04/cell) and 1h (0.18±0.04/cell) after the first injection and at 5min and 1h after the second injection (0.21±0.03 and 0.19±0.04/cell, respectively; p=0.003 for both). At 24h after the first and second injections, the number of DSB foci had returned to baseline (0.06±0.02 and 0.12±0.05/cell, respectively). 99m Tc activity levels in peripheral blood samples correlated well with DSB counts (r=0.451). DSB counts reflect 99m Tc-MIBI activity after injection for two-day MPS, and might allow individual monitoring of biological effects of cardiac nuclear imaging. • Myocardial perfusion scintigraphy using 99m Tc induces time-dependent double-strand breaks (DSBs) • γ-H2AX immunofluorescence microscopy shows DSB as an early response to radiotracer injection • Activity measurements of 99m Tc correlate well with detected DSB • DSB foci induced by 99m Tc return to baseline 24h after radiotracer injection.

Natural polymer-stabilized multiple water-in-oil-in-water emulsions: a novel dermal drug delivery system for 5-fluorouracil.

PubMed

Hoppel, Magdalena; Mahrhauser, Denise; Stallinger, Christina; Wagner, Florian; Wirth, Michael; Valenta, Claudia

2014-05-01

The aim of this study was to create multiple water-in-oil-in-water (W/O/W) emulsions with an increased long-term stability as skin delivery systems for the hydrophilic model drug 5-fluorouracil. Multiple W/O/W emulsions were prepared in a one-step emulsification process, and were characterized regarding particle size, microstructure and viscosity. In-vitro studies on porcine skin with Franz-type diffusion cells, tape stripping experiments and attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR) were performed. The addition of Solagum AX, a natural polymer mixture of acacia and xanthan gum, led to multiple W/O/W emulsions with a remarkably increased long-term stability in comparison to formulations without a thickener. The higher skin diffusion of 5-fluorouracil from the multiple emulsions compared with an O/W-macroemulsion could be explained by ATR-FTIR. Shifts to higher wave numbers and increase of peak areas of the asymmetric and symmetric CH2 stretching vibrations confirmed a transition of parts of the skin lipids from an ordered to a disordered state after impregnation of porcine skin with the multiple emulsions. Solagum AX is highly suitable for stabilization of the created multiple emulsions. Moreover, these formulations showed superiority over a simple O/W-macroemulsion regarding skin permeation and penetration of 5-fluorouracil. © 2013 Royal Pharmaceutical Society.

Near-infrared counterparts of three transient very faint neutron star X-ray binaries

NASA Astrophysics Data System (ADS)

Shaw, A. W.; Heinke, C. O.; Degenaar, N.; Wijnands, R.; Kaur, R.; Forestell, L. M.

2017-10-01

We present near-infrared (NIR) imaging observations of three transient neutron star X-ray binaries, SAX J1753.5-2349, SAX J1806.5-2215 and AX J1754.2-2754. All three sources are members of the class of 'very faint' X-ray transients which exhibit X-ray luminosities LX ≲ 1036 erg s-1. The nature of this class of sources is still poorly understood. We detect NIR counterparts for all three systems and perform multiband photometry for both SAX J1753.5-2349 and SAX J1806.5-2215, including narrow-band Br γ photometry for SAX J1806.5-2215. We find that SAX J1753.5-2349 is significantly redder than the field population, indicating that there may be absorption intrinsic to the system, or perhaps a jet is contributing to the infrared emission. SAX J1806.5-2215 appears to exhibit absorption in Br γ, providing evidence for hydrogen in the system. Our observations of AX J1754.2-2754 represent the first detection of an NIR counterpart for this system. We find that none of the measured magnitudes are consistent with the expected quiescent magnitudes of these systems. Assuming that the infrared radiation is dominated by either the disc or the companion star, the observed magnitudes argue against an ultracompact nature for all three systems.

Self-compensation in arsenic doping of CdTe

DOE PAGES

Ablekim, Tursun; Swain, Santosh K.; Yin, Wan -Jian; ...

2017-07-04

Efficient p-type doping in CdTe has remained a critical challenge for decades, limiting the performance of CdTe-based semiconductor devices. Arsenic is a promising p-type dopant; however, reproducible doping with high concentration is difficult and carrier lifetime is low. We systematically studied defect structures in As-doped CdTe using high-purity single crystal wafers to investigate the mechanisms that limit p-type doping. Two As-doped CdTe with varying acceptor density and two undoped CdTe were grown in Cd-rich and Te-rich environments. The defect structures were investigated by thermoelectric-effect spectroscopy (TEES), and first-principles calculations were used for identifying and assigning the experimentally observed defects. Measurementsmore » revealed activation of As is very low in both As-doped samples with very short lifetimes indicating strong compensation and the presence of significant carrier trapping defects. Defect studies suggest two acceptors and one donor level were introduced by As doping with activation energies at ~88 meV, ~293 meV and ~377 meV. In particular, the peak shown at ~162 K in the TEES spectra is very prominent in both As-doped samples, indicating a signature of AX-center donors. In conclusion, the AX-centers are believed to be responsible for most of the compensation because of their low formation energy and very prominent peak intensity in TEES spectra.« less

Self-compensation in arsenic doping of CdTe

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

Ablekim, Tursun; Swain, Santosh K.; Yin, Wan -Jian

Efficient p-type doping in CdTe has remained a critical challenge for decades, limiting the performance of CdTe-based semiconductor devices. Arsenic is a promising p-type dopant; however, reproducible doping with high concentration is difficult and carrier lifetime is low. We systematically studied defect structures in As-doped CdTe using high-purity single crystal wafers to investigate the mechanisms that limit p-type doping. Two As-doped CdTe with varying acceptor density and two undoped CdTe were grown in Cd-rich and Te-rich environments. The defect structures were investigated by thermoelectric-effect spectroscopy (TEES), and first-principles calculations were used for identifying and assigning the experimentally observed defects. Measurementsmore » revealed activation of As is very low in both As-doped samples with very short lifetimes indicating strong compensation and the presence of significant carrier trapping defects. Defect studies suggest two acceptors and one donor level were introduced by As doping with activation energies at ~88 meV, ~293 meV and ~377 meV. In particular, the peak shown at ~162 K in the TEES spectra is very prominent in both As-doped samples, indicating a signature of AX-center donors. In conclusion, the AX-centers are believed to be responsible for most of the compensation because of their low formation energy and very prominent peak intensity in TEES spectra.« less

Intermediate frequency magnetic field generated by a wireless power transmission device does not cause genotoxicity in vitro.

PubMed

Shi, Dejing; Zhu, Chunbo; Lu, Rengui; Mao, Shitong; Qi, Yanhua

2014-10-01

The aim of this study was to evaluate effects of intermediate frequency magnetic fields (IFMF) generated by a wireless power transmission (WPT) based on magnetic resonance from the perspective of cellular genotoxicity on cultured human lens epithelial cells (HLECs). We evaluated the effects of exposure to 90 kHz magnetic fields at 93.36 µT on cellular genotoxicity in vitro for 2 and 4 h. The magnetic flux density is approximately 3.5 times higher than the reference level recommended by the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines. For assessment of genotoxicity, we studied cellular proliferation, apoptosis and DNA damage by Cell Counting Kit-8 (CCK-8) assay, flow cytometry analysis, alkaline comet assay and phosphorylated histone H2AX (γH2AX) foci formation test. We did not detect any effect of a 90 kHz IFMF generated by WPT based on magnetic resonance on cell proliferation, apoptosis, comet assay, and γH2AX foci formation test. Our results indicated that exposure to 90 kHz IFMF generated by WPT based on magnetic resonance at 93.36 µT for 2 and 4 h does not cause detectable cellular genotoxicity. © 2014 Wiley Periodicals, Inc.

The role of gigaxonin in the degradation of the glial-specific intermediate filament protein GFAP

PubMed Central

Lin, Ni-Hsuan; Huang, Yu-Shan; Opal, Puneet; Goldman, Robert D.; Messing, Albee; Perng, Ming-Der

2016-01-01

Alexander disease (AxD) is a primary genetic disorder of astrocytes caused by dominant mutations in the gene encoding the intermediate filament (IF) protein GFAP. This disease is characterized by excessive accumulation of GFAP, known as Rosenthal fibers, within astrocytes. Abnormal GFAP aggregation also occurs in giant axon neuropathy (GAN), which is caused by recessive mutations in the gene encoding gigaxonin. Given that one of the functions of gigaxonin is to facilitate proteasomal degradation of several IF proteins, we sought to determine whether gigaxonin is involved in the degradation of GFAP. Using a lentiviral transduction system, we demonstrated that gigaxonin levels influence the degradation of GFAP in primary astrocytes and in cell lines that express this IF protein. Gigaxonin was similarly involved in the degradation of some but not all AxD-associated GFAP mutants. In addition, gigaxonin directly bound to GFAP, and inhibition of proteasome reversed the clearance of GFAP in cells achieved by overexpressing gigaxonin. These studies identify gigaxonin as an important factor that targets GFAP for degradation through the proteasome pathway. Our findings provide a critical foundation for future studies aimed at reducing or reversing pathological accumulation of GFAP as a potential therapeutic strategy for AxD and related diseases. PMID:27798231

AZD1775 sensitizes T cell acute lymphoblastic leukemia cells to cytarabine by promoting apoptosis over DNA repair.

PubMed

Ford, James B; Baturin, Dmitry; Burleson, Tamara M; Van Linden, Annemie A; Kim, Yong-Mi; Porter, Christopher C

2015-09-29

While some children with acute lymphoblastic leukemia (ALL) have excellent prognoses, the prognosis for adults and children with T cell ALL is more guarded. Treatment for T-ALL is heavily dependent upon antimetabolite chemotherapeutics, including cytarabine. Targeted inhibition of WEE1 with AZD1775 has emerged as a strategy to sensitize cancer cells to cytarabine and other chemotherapeutics. We sought to determine if this strategy would be effective for T-ALL with clinically relevant anti-leukemia agents. We found that AZD1775 sensitizes T-ALL cells to several traditional anti-leukemia agents, acting synergistically with cytarabine by enhancing DNA damage and apoptosis. In addition to increased phosphorylation of H2AX at serine 139 (γH2AX), AZD1775 led to increased phosphorylation of H2AX at tyrosine 142, a signaling event associated with promotion of apoptosis over DNA repair. In a xenograft model of T-ALL, the addition of AZD1775 to cytarabine slowed leukemia progression and prolonged survival. Inhibition of WEE1 with AZD1775 sensitizes T-ALL to several anti-leukemia agents, particularly cytarabine and that mechanistically, AZD1775 promotes apoptosis over DNA repair in cells treated with cytarabine. These data support the development of clinical trials including AZD1775 in combination with conventional chemotherapy for acute leukemia.

AZD1775 sensitizes T cell acute lymphoblastic leukemia cells to cytarabine by promoting apoptosis over DNA repair

PubMed Central

Burleson, Tamara M.; Van Linden, Annemie A.; Kim, Yong-Mi; Porter, Christopher C.

2015-01-01

While some children with acute lymphoblastic leukemia (ALL) have excellent prognoses, the prognosis for adults and children with T cell ALL is more guarded. Treatment for T-ALL is heavily dependent upon antimetabolite chemotherapeutics, including cytarabine. Targeted inhibition of WEE1 with AZD1775 has emerged as a strategy to sensitize cancer cells to cytarabine and other chemotherapeutics. We sought to determine if this strategy would be effective for T-ALL with clinically relevant anti-leukemia agents. We found that AZD1775 sensitizes T-ALL cells to several traditional anti-leukemia agents, acting synergistically with cytarabine by enhancing DNA damage and apoptosis. In addition to increased phosphorylation of H2AX at serine 139 (γH2AX), AZD1775 led to increased phosphorylation of H2AX at tyrosine 142, a signaling event associated with promotion of apoptosis over DNA repair. In a xenograft model of T-ALL, the addition of AZD1775 to cytarabine slowed leukemia progression and prolonged survival. Inhibition of WEE1 with AZD1775 sensitizes T-ALL to several anti-leukemia agents, particularly cytarabine. Mechanistically, AZD1775 promotes apoptosis over DNA repair in cells treated with cytarabine. These data support the development of clinical trials including AZD1775 in combination with conventional chemotherapy for acute leukemia. PMID:26334102

Application of probabilistic fiber-tracking method of MR imaging to measure impact of cranial irradiation on structural brain connectivity in children treated for medulloblastoma

NASA Astrophysics Data System (ADS)

Duncan, Elizabeth C.; Reddick, Wilburn E.; Glass, John O.; Hyun, Jung Won; Ji, Qing; Li, Yimei; Gajjar, Amar

2016-03-01

We applied a modified probabilistic fiber-tracking method for the extraction of fiber pathways to quantify decreased white matter integrity as a surrogate of structural loss in connectivity due to cranial radiation therapy (CRT) as treatment for pediatric medulloblastoma. Thirty subjects were examined (n=8 average-risk, n=22 high-risk) and the groups did not differ significantly in age at examination. The pathway analysis created a structural connectome focused on sub-networks within the central executive network (CEN) for comparison between baseline and post-CRT scans and for comparison between standard and high dose CRT. A paired-wise comparison of the connectivity between baseline and post-CRT scans showed the irradiation did have a significant detrimental impact on white matter integrity (decreased fractional anisotropy (FA) and decreased axial diffusivity (AX)) in most of the CEN sub-networks. Group comparisons of the change in the connectivity revealed that patients receiving high dose CRT experienced significant AX decreases in all sub-networks while the patients receiving standard dose CRT had relatively stable AX measures across time. This study on pediatric patients with medulloblastoma demonstrated the utility of this method to identify specific sub-networks within the developing brain affected by CRT.

EGb 761 Protects Cardiac Microvascular Endothelial Cells against Hypoxia/Reoxygenation Injury and Exerts Inhibitory Effect on the ATM Pathway.

PubMed

Zhang, Chao; Wang, Deng-Feng; Zhang, Zhuang; Han, Dong; Yang, Kan

2017-03-28

Ginkgo bilob a extract (EGb 761) has been widely used clinically to reduce myocardial ischemia reperfusion injury (MIRI). Microvascular endothelial cells (MVECs) may be a proper cellular model in vitro for the effect and mechanism study against MIRI. However, the protective effect of EGb 761 on MVECs resisting hypoxia/reoxygenation (H/R) injury is little reported. In this study, H/R-injured MVECs were treated with EGb 761, and then the cell viability, apoptosis, ROS production, SOD activity, caspase-3 activity, and protein level of ATM, γ-H2AX, p53, and Bax were measured. ATM siRNA was transfected to study the changes of protein in the ATM pathway. EGb 761 presented protective effect on H/R-injured MVECs, with decreasing cell death, apoptosis, and ROS, and elevated SOD activity. Next, EGb 761 could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax in a dose-dependent manner. Moreover, ATM siRNA also could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax. Overall, these findings verify that EGb 761 protects cardiac MVECs from H/R injury, and for the first time, illustrate the influence on the ATM pathway and apoptosis by EGb 761 via dampening ROS.

Genoprotective effect of hyaluronic acid against benzalkonium chloride-induced DNA damage in human corneal epithelial cells

PubMed Central

Wu, Han; Zhang, Huina; Wang, Changjun; Wu, Yihua; Xie, Jiajun; Jin, Xiuming; Yang, Jun

2011-01-01

Purpose The aim of this study was to investigate hyaluronic acid (HA) protection on cultured human corneal epithelial cells (HCEs) against benzalkonium chloride (BAC)-induced DNA damage and intracellular reactive oxygen species (ROS) increase. Methods Cells were incubated with different concentrations of BAC with or without the presence of 0.2% HA for 30 min. DNA damage to HCEs was examined by alkaline comet assay and by immunofluorescence microscopic detection of the phosphorylated form of histone variant H2AX (γH2AX) foci. ROS production was assessed by the fluorescent probe, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Cell apoptosis was determined with annexin V staining by flow cytometry. Results HA significantly reduced BAC-induced DNA damage as indicated by the tail length (TL) and tail moment (TM) of alkaline comet assay and by γH2AX foci formation, respectively. Moreover, HA significantly decreased BAC-induced ROS increase and cell apoptosis. However, exposure to HA alone did not produce any significant change in DNA damage, ROS generation, or cell apoptosis. Conclusions BAC could induce DNA damage and cell apoptosis in HCEs, probably through increasing oxidative stress. Furthermore, HA was an effective protective agent that had antioxidant properties and could decrease DNA damage and cell apoptosis induced by BAC. PMID:22219631

Pannus inflammation in sacroiliitis following immune pathological injury and radiological structural damage: a study of 193 patients with spondyloarthritis.

PubMed

Wang, Dan Min; Lin, Ling; Peng, Jian Hua; Gong, Yao; Hou, Zhi Duo; Chen, Su Biao; Xiao, Zheng Yu

2018-06-08

The pathogenesis of sacroiliitis is unclear; therefore, we aimed to systematically study the immunopathology of sacroiliitis in patients with axial spondyloarthritis (axSpA), and explore the relationship between pannus formation, inflammation, and the structural damage caused by sacroiliitis. Fine needle aspiration biopsy of the sacroiliac joint (SIJ) was performed in 193 patients with axSpA. Clinical, laboratory, and imaging data were collected at baseline and during the follow up. Immunohistochemistry analysis was performed to detect CD34+ microvessels, CD68+ osteoclasts/macrophages, vascular endothelial growth factor (VEGF), metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), and caspase-3. Autopsy subjects were used as controls. In early sacroiliitis (grade 0-1) all pathological features could be observed, with the most common being subchondral pannus formation. Among the 193 patients, 98 were followed up for 1-13 years (mean 3.6 years); 63.3% had radiological progression at the endpoint. Multiple regression analysis showed that cartilage pannus invasion (OR 2.99, P = 0.010) and endochondral ossification (OR 3.97, P = 0.049) at baseline were risk factors for radiological structural damage. Compared to SIJ controls, the subchondral microvessel density, number of CD68+ multinuclear osteoclasts, and the levels of VEGF, caspase-3, MMP-3, and TNF-α expressed at the interface of the bone and cartilage were significantly higher in patients with sacroiliitis. Subchondral fibrovascular tissue formation is the most important pathological feature in early sacroiliitis. The existence of cartilage pannus invasion or endochondral ossification at baseline can predict radiological structural damage during the follow up.

FIRE_AX_SOF_ARAT_FLT

Atmospheric Science Data Center

2015-11-25

... Microwave Radiometer Optical Counter Platinum Resistance Pyranometer Pyrgeometer Variable Capacitance ... Parameters:  Aerosol Particle Properties Air Temperature Cloud Liquid Water Deiced Temperature Dew Point Doppler ...

DNA damage predicts prognosis and treatment response in colorectal liver metastases superior to immunogenic cell death and T cells

PubMed Central

Laengle, Johannes; Stift, Judith; Bilecz, Agnes; Wolf, Brigitte; Beer, Andrea; Hegedus, Balazs; Stremitzer, Stefan; Starlinger, Patrick; Tamandl, Dietmar; Pils, Dietmar; Bergmann, Michael

2018-01-01

Preclinical models indicate that DNA damage induces type I interferon (IFN), which is crucial for the induction of an anti-tumor immune response. In human cancers, however, the association between DNA damage and an immunogenic cell death (ICD), including the release and sensing of danger signals, the subsequent ER stress response and a functional IFN system, is less clear. Methods: Neoadjuvant-treated colorectal liver metastases (CLM) patients, undergoing liver resection in with a curative intent, were retrospectively enrolled in this study (n=33). DNA damage (γH2AX), RNA and DNA sensors (RIG-I, DDX41, cGAS, STING), ER stress response (p-PKR, p-eIF2α, CALR), type I and type II IFN- induced proteins (MxA, GBP1), mature dendritic cells (CD208), and cytotoxic and memory T cells (CD3, CD8, CD45RO) were investigated by an immunohistochemistry whole-slide tissue scanning approach and further correlated with recurrence-free survival (RFS), overall survival (OS), radiographic and pathologic therapy response. Results: γH2AX is a negative prognostic marker for RFS (HR 1.32, 95% CI 1.04-1.69, p=0.023) and OS (HR 1.61, 95% CI 1.23-2.11, p<0.001). A model comprising of DDX41, STING and p-PKR predicts radiographic therapy response (AUC=0.785, p=0.002). γH2AX predicts prognosis superior to the prognostic value of CD8. CALR positively correlates with GBP1, CD8 and cGAS. A model consisting of γH2AX, p-eIF2α, DDX41, cGAS, CD208 and CD45RO predicts pathological therapy response (AUC=0.944, p<0.001). Conclusion: In contrast to preclinical models, DNA damage inversely correlated with ICD and its associated T cell infiltrate and potentially serves as a therapeutic target in CLM. PMID:29930723

Alanine-170 and proline-172 are critical determinants for extracellular CD20 epitopes; heterogeneity in the fine specificity of CD20 monoclonal antibodies is defined by additional requirements imposed by both amino acid sequence and quaternary structure.

PubMed

Polyak, Maria J; Deans, Julie P

2002-05-01

In vivo ablation of malignant B cells can be achieved using antibodies directed against the CD20 antigen. Fine specificity differences among CD20 monoclonal antibodies (mAbs) are assumed not to be a factor in determining their efficacy because evidence from antibody-blocking studies indicates limited epitope diversity with only 2 overlapping extracellular CD20 epitopes. However, in this report a high degree of heterogeneity among antihuman CD20 mAbs is demonstrated. Mutation of alanine and proline at positions 170 and 172 (AxP) (single-letter amino acid codes; x indicates the identical amino acid at the same position in the murine and human CD20 sequences) in human CD20 abrogated the binding of all CD20 mAbs tested. Introduction of AxP into the equivalent positions in the murine sequence, which is not otherwise recognized by antihuman CD20 mAbs, fully reconstituted the epitope recognized by B1, the prototypic anti-CD20 mAb. 2H7, a mAb previously thought to recognize the same epitope as B1, did not recognize the murine AxP mutant. Reconstitution of the 2H7 epitope was achieved with additional mutations replacing VDxxD in the murine sequence for INxxN (positions 162-166 in the human sequence). The integrity of the 2H7 epitope, unlike that of B1, further depends on the maintenance of CD20 in an oligomeric complex. The majority of 16 antihuman CD20 mAbs tested, including rituximab, bound to murine CD20 containing the AxP mutations. Heterogeneity in the fine specificity of these antibodies was indicated by marked differences in their ability to induce homotypic cellular aggregation and translocation of CD20 to a detergent-insoluble membrane compartment previously identified as lipid rafts.

Strain-induced tetragonal distortions and multiferroic properties in polycrystalline Sr1 -xB axMn O3 (x =0.43 -0.45 ) perovskites

NASA Astrophysics Data System (ADS)

Somaily, H.; Kolesnik, S.; Mais, J.; Brown, D.; Chapagain, K.; Dabrowski, B.; Chmaissem, O.

2018-05-01

We report the structure-property phase diagram of unique single-ion type-1 multiferroic pseudocubic Sr1 -xB axMn O3 perovskites. Employing a specially designed multistep reduction-oxidation synthesis technique, we have synthesized Sr1 -xB axMn O3 compositions in their polycrystalline form with a significantly extended Ba solubility limit that is only rivaled by a very limited number of crystals and thin films grown under nonequilibrium conditions. Understanding the multiferroic interplay with structure in Sr1 -xB axMn O3 is of great importance as it opens the door wide to the development of newer materials from the parent (A A' ) (B B' ) O3 system with enhanced properties. To this end, using a combination of time-of-flight neutron and synchrotron x-ray scattering techniques, we determined the exact structures and quantified the Mn and oxygen polar distortions above and below the ferroelectric Curie temperature TC and the Néel temperature TN. In its ferroelectric state, the system crystalizes in the noncentrosymmetric tetragonal P 4 m m space group, which gives rise to a large electric dipole moment Ps, in the z direction, of 18.4 and 29.5 μ C /c m2 for x =0.43 and 0.45, respectively. The two independently driven ferroelectric and magnetic order parameters are single-handedly accommodated by the Mn sublattice leading to a novel strain-assisted multiferroic behavior in agreement with many theoretical predictions. Our neutron diffraction results demonstrate the large and tunable suppression of the ferroelectric order at the onset of AFM ordering and confirm the coexistence and strong coupling of the two ferroic orders below TN. The refined magnetic moments confirm the strong covalent bonding between Mn and the oxygen anions, which is necessary for stabilizing the ferroelectric phase.

Increased uncoupling protein-2 mRNA abundance and glucocorticoid action in adipose tissue in the sheep fetus during late gestation is dependent on plasma cortisol and triiodothyronine

PubMed Central

Gnanalingham, MG; Mostyn, A; Forhead, AJ; Fowden, AL; Symonds, ME; Stephenson, T

2005-01-01

The endocrine regulation of uncoupling protein-2 (UCP2), an inner mitochondrial protein, in fetal adipose tissue remains unclear. The present study aimed to determine if fetal plasma cortisol and triiodothyronine (T3) influenced the mRNA abundance of UCP2, glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and 2 (11βHSD2) in fetal adipose tissue in the sheep during late gestation. Perirenal–abdominal adipose tissue was sampled from ovine fetuses to which either cortisol (2–3 mg kg−1 day−1) or saline was infused for 5 days up to 127–130 days gestation, or near term fetuses (i.e. 142–145 days gestation) that were either adrenalectomised (AX) or remained intact. Fetal plasma cortisol and T3 concentrations were higher in the cortisol infused animals and lower in AX fetuses compared with their corresponding control group, and increased with gestational age. UCP2 and GR mRNA abundance were significantly lower in AX fetuses compared with age-matched controls, and increased with gestational age and by cortisol infusion. Glucocorticoid action in fetal adipose tissue was augmented by AX and suppressed by cortisol infusion, the latter also preventing the gestational increase in 11βHSD1 mRNA and decrease in 11βHSD2 mRNA. When all treatment groups were combined, both fetal plasma cortisol and T3 concentrations were positively correlated with UCP2, GR and 11βHSD2 mRNA abundance, but negatively correlated with 11βHSD1 mRNA abundance. In conclusion, plasma cortisol and T3 are both required for the late gestation rise in UCP2 mRNA and differentially regulate glucocorticoid action in fetal adipose tissue in the sheep during late gestation. PMID:15961419

Synchrotron-based imaging of chromium and γ-H2AX immunostaining in the duodenum following repeated exposure to Cr(VI) in drinking water.

PubMed

Thompson, Chad M; Seiter, Jennifer; Chappell, Mark A; Tappero, Ryan V; Proctor, Deborah M; Suh, Mina; Wolf, Jeffrey C; Haws, Laurie C; Vitale, Rock; Mittal, Liz; Kirman, Christopher R; Hays, Sean M; Harris, Mark A

2015-01-01

Current drinking water standards for chromium are for the combined total of both hexavalent and trivalent chromium (Cr(VI) and Cr(III)). However, recent studies have shown that Cr(III) is not carcinogenic to rodents, whereas mice chronically exposed to high levels of Cr(VI) developed duodenal tumors. These findings may suggest the need for environmental standards specific for Cr(VI). Whether the intestinal tumors arose through a mutagenic or non-mutagenic mode of action (MOA) greatly impacts how drinking water standards for Cr(VI) are derived. Herein, X-ray fluorescence (spectro)microscopy (µ-XRF) was used to image the Cr content in the villus and crypt regions of duodena from B6C3F1 mice exposed to 180 mg/l Cr(VI) in drinking water for 13 weeks. DNA damage was also assessed by γ-H2AX immunostaining. Exposure to Cr(VI) induced villus blunting and crypt hyperplasia in the duodenum--the latter evidenced by lengthening of the crypt compartment by ∼2-fold with a concomitant 1.5-fold increase in the number of crypt enterocytes. γ-H2AX immunostaining was elevated in villi, but not in the crypt compartment. µ-XRF maps revealed mean Cr levels >30 times higher in duodenal villi than crypt regions; mean Cr levels in crypt regions were only slightly above background signal. Despite the presence of Cr and elevated γ-H2AX immunoreactivity in villi, no aberrant foci indicative of transformation were evident. These findings do not support a MOA for intestinal carcinogenesis involving direct Cr-DNA interaction in intestinal stem cells, but rather support a non-mutagenic MOA involving chronic wounding of intestinal villi and crypt cell hyperplasia. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology.

Enhanced susceptibility of ovaries from obese mice to 7,12-dimethylbenz[a]anthracene-induced DNA damage

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

Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Nteeba, Jackson, E-mail: nteeba@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

7,12-Dimethylbenz[a]anthracene (DMBA) depletes ovarian follicles and induces DNA damage in extra-ovarian tissues, thus, we investigated ovarian DMBA-induced DNA damage. Additionally, since obesity is associated with increased offspring birth defect incidence, we hypothesized that a DMBA-induced DNA damage response (DDR) is compromised in ovaries from obese females. Wild type (lean) non agouti (a/a) and KK.Cg-Ay/J heterozygote (obese) mice were dosed with sesame oil or DMBA (1 mg/kg; intraperitoneal injection) at 18 weeks of age, for 14 days. Total ovarian RNA and protein were isolated and abundance of Ataxia telangiectasia mutated (Atm), X-ray repair complementing defective repair in Chinese hamster cells 6more » (Xrcc6), breast cancer type 1 (Brca1), Rad 51 homolog (Rad51), poly [ADP-ribose] polymerase 1 (Parp1) and protein kinase, DNA-activated, catalytic polypeptide (Prkdc) were quantified by RT-PCR or Western blot. Phosphorylated histone H2AX (γH2AX) level was determined by Western blotting. Obesity decreased (P < 0.05) basal protein abundance of PRKDC and BRCA1 proteins but increased (P < 0.05) γH2AX and PARP1 proteins. Ovarian ATM, XRCC6, PRKDC, RAD51 and PARP1 proteins were increased (P < 0.05) by DMBA exposure in lean mice. A blunted DMBA-induced increase (P < 0.05) in XRCC6, PRKDC, RAD51 and BRCA1 was observed in ovaries from obese mice, relative to lean counterparts. Taken together, DMBA exposure induced γH2AX as well as the ovarian DDR, supporting that DMBA causes ovarian DNA damage. Additionally, ovarian DDR was partially attenuated in obese females raising concern that obesity may be an additive factor during chemical-induced ovotoxicity. - Highlights: • DMBA induces markers of ovarian DNA damage. • Obesity induces low level ovarian DNA damage. • DMBA-induced DNA repair response is altered by obesity.« less

Identification and Characterization of Non-Cellulose-Producing Mutants of Gluconacetobacter hansenii Generated by Tn5 Transposon Mutagenesis

PubMed Central

Deng, Ying; Nagachar, Nivedita; Xiao, Chaowen; Tien, Ming

2013-01-01

The acs operon of Gluconacetobacter is thought to encode AcsA, AcsB, AcsC, and AcsD proteins that constitute the cellulose synthase complex, required for the synthesis and secretion of crystalline cellulose microfibrils. A few other genes have been shown to be involved in this process, but their precise role is unclear. We report here the use of Tn5 transposon insertion mutagenesis to identify and characterize six non-cellulose-producing (Cel−) mutants of Gluconacetobacter hansenii ATCC 23769. The genes disrupted were acsA, acsC, ccpAx (encoding cellulose-complementing protein [the subscript “Ax” indicates genes from organisms formerly classified as Acetobacter xylinum]), dgc1 (encoding guanylate dicyclase), and crp-fnr (encoding a cyclic AMP receptor protein/fumarate nitrate reductase transcriptional regulator). Protein blot analysis revealed that (i) AcsB and AcsC were absent in the acsA mutant, (ii) the levels of AcsB and AcsC were significantly reduced in the ccpAx mutant, and (iii) the level of AcsD was not affected in any of the Cel− mutants. Promoter analysis showed that the acs operon does not include acsD, unlike the organization of the acs operon of several strains of closely related Gluconacetobacter xylinus. Complementation experiments confirmed that the gene disrupted in each Cel− mutant was responsible for the phenotype. Quantitative real-time PCR and protein blotting results suggest that the transcription of bglAx (encoding β-glucosidase and located immediately downstream from acsD) was strongly dependent on Crp/Fnr. A bglAx knockout mutant, generated via homologous recombination, produced only ∼16% of the wild-type cellulose level. Since the crp-fnr mutant did not produce any cellulose, Crp/Fnr may regulate the expression of other gene(s) involved in cellulose biosynthesis. PMID:24013627

In-depth study of long-term variability in the X-ray emission of the Be/X-ray binary system AX J0049.4-7323

NASA Astrophysics Data System (ADS)

Ducci, L.; Romano, P.; Malacaria, C.; Ji, L.; Bozzo, E.; Santangelo, A.

2018-06-01

AX J0049.4-7323 is a Be/X-ray binary in the Small Magellanic Cloud hosting a 750 s pulsar which has been observed over the last 17 years by several X-ray telescopes. Despite numerous observations, little is known about its X-ray behaviour. Therefore, we coherently analysed archival Swift, Chandra, XMM-Newton, RXTE, and INTEGRAL data, and we compared them with already published ASCA data, to study its X-ray long-term spectral and flux variability. AX J0049.4-7323 shows a high X-ray variability, spanning more than three orders of magnitudes, from L ≈ 1.6 × 1037 erg s-1 (0.3-8 keV, d = 62 kpc) down to L ≈ 8 × 1033 erg s-1. RXTE, Chandra, Swift, and ASCA observed, in addition to the expected enhancement of X-ray luminosity at periastron, flux variations by a factor of 270 with peak luminosities of ≈2.1 × 1036 erg s-1 far from periastron. These properties are difficult to reconcile with the typical long-term variability of Be/XRBs, traditionally interpreted in terms of type I and type II outbursts. The study of AX J0049.4-7323 is complemented with a spectral analysis of Swift, Chandra, and XMM-Newton data which showed a softening trend when the emission becomes fainter, and an analysis of optical/UV data collected by the UVOT telescope on board Swift. In addition, we measured a secular spin-up rate of Ṗ = (-3.00 ± 0.12) × 10-3 s day-1, which suggests that the pulsar has not yet achieved its equilibrium period. Assuming spherical accretion, we estimated an upper limit for the magnetic field strength of the pulsar of ≈3 × 1012 G.

The Inhibitory Effects of Anti-Oxidants on Ultraviolet-Induced Up-Regulation of the Wrinkling-Inducing Enzyme Neutral Endopeptidase in Human Fibroblasts

PubMed Central

Nakajima, Hiroaki; Terazawa, Shuko; Niwano, Takao; Yamamoto, Yorihiro; Imokawa, Genji

2016-01-01

We recently reported that the over-expression of skin fibroblast-derived neutral endopeptidase (NEP) plays a pivotal role in impairing the three-dimensional architecture of dermal elastic fibers during the biological mechanism of ultraviolet (UV)-induced skin wrinkling. In that process, a UVB-associated epithelial-mesenchymal cytokine interaction as well as a direct UVA-induced cellular stimulation are associated with the up-regulation of NEP in human fibroblasts. In this study, we characterized the mode of action of ubiquinol10 which may abrogate the up-regulation of NEP by dermal fibroblasts, resulting in a reported in vivo anti-wrinkling action, and compared that with 3 other anti-oxidants, astaxanthin (AX), riboflavin (RF) and flavin mononucleotide (FMN). Post-irradiation treatment with all 4 of those anti-oxidants elicited an interrupting effect on the UVB-associated epithelial-mesenchymal cytokine interaction leading to the up-regulation of NEP in human fibroblasts but with different modes of action. While AX mainly served as an inhibitor of the secretion of wrinkle-inducing cytokines, such as interleukin-1α (IL-1α) and granulocyte macrophage colony stimulatory factor (GM-CSF) in UVB-exposed epidermal keratinocytes, ubiquinol10, RF and FMN predominantly interrupted the IL-1α and GM-CSF-stimulated expression of NEP in dermal fibroblasts. On the other hand, as for the UVA-associated mechanism, similar to the abrogating effects reported for AX and FMN, ubiquinol10 but not RF had the potential to abrogate the increased expression of NEP and matrix-metalloproteinase-1 in UVA-exposed human fibroblasts. Our findings strongly support the in vivo anti-wrinkling effects of ubiquinol10 and AX on human and animal skin and provide convincing proof of the UV-induced wrinkling mechanism that essentially focuses on the over-expression of NEP by dermal fibroblasts as an intrinsic causative factor. PMID:27648570

DNA damage response in renal ischemia-reperfusion and ATP-depletion injury of renal tubular cells.

PubMed

Ma, Zhengwei; Wei, Qingqing; Dong, Guie; Huo, Yuqing; Dong, Zheng

2014-07-01

Renal ischemia-reperfusion leads to acute kidney injury (AKI) that is characterized pathologically by tubular damage and cell death, followed by tubular repair, atrophy and interstitial fibrosis. Recent work suggested the possible presence of DNA damage response (DDR) in AKI. However, the evidence is sketchy and the role and regulation of DDR in ischemic AKI remain elusive. In this study, we demonstrated the induction of phosphorylation of ATM, H2AX, Chk2 and p53 during renal ischemia-reperfusion in mice, suggesting DDR in kidney tissues. DDR was also induced in vitro during the recovery or "reperfusion" of renal proximal tubular cells (RPTCs) after ATP depletion. DDR in RPTCs was abrogated by supplying glucose to maintain ATP via glycolysis, indicating that the DDR depends on ATP depletion. The DDR was also suppressed by the general caspase inhibitor z-VAD and the overexpression of Bcl-2, supporting a role of apoptosis-associated DNA damage in the DDR. N-acetylcysteine (NAC), an antioxidant, suppressed the phosphorylation of ATM and p53 and, to a less extent, Chk2, but NAC increased the phosphorylation and nuclear foci formation of H2AX. Interestingly, NAC increased apoptosis, which may account for the observed H2AX activation. Ku55933, an ATM inhibitor, blocked ATM phosphorylation and ameliorated the phosphorylation of Chk2 and p53, but it increased H2AX phosphorylation and nuclear foci formation. Ku55933 also increased apoptosis in RPTCs following ATP depletion. The results suggest that DDR occurs during renal ischemia-reperfusion in vivo and ATP-depletion injury in vitro. The DDR is partially induced by apoptosis and oxidative stress-related DNA damage. ATM, as a sensor in the DDR, may play a cytoprotective role against tubular cell injury and death. Copyright © 2014 Elsevier B.V. All rights reserved.

REDOSER project: optimising biological therapy dose for rheumatoid arthritis and spondyloarthritis patients.

PubMed

González-Álvaro, Isidoro; Blasco, Antonio J; Lázaro, Pablo; Sánchez-Piedra, Carlos; Almodovar, Raquel; Bachiller-Corral, Javier; Balsa, Alejandro; Caliz, Rafael; Candelas, Gloria; Fernández-Carballido, Cristina; García-Aparicio, Angel; García-Magallón, Blanca; García-Vicuña, Rosario; Gómez-Centeno, Antonio; Ortiz, Ana M; Sanmartí, Raimon; Sanz, Jesús; Tejera, Beatriz

2017-11-01

Reducing the dose of biological therapy (BT) when patients with immune-mediated arthritis achieve a sustained therapeutic goal may help to decrease costs for national health services and reduce the risk of serious infection. However, there is little information about whether such a decision can be applied universally. Therefore, the objective of this study was to develop appropriateness criteria for reducing the dose of BT in patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and peripheral spondyloarthritis (pSpA). The RAND/UCLA appropriateness method was coordinated by experts in the methodology. Five rheumatologists with clinical research experience in RA and/or SpA selected and precisely defined the variables considered relevant when deciding to reduce the dose of BT in the 3 diseases, in order to define patient profiles. Ten rheumatologists with experience in prescribing BT anonymously rated each profile on a scale of 1 (completely inappropriate) to 9 (completely appropriate) after revising a summary of the evidence obtained from 4 systematic literature reviews carried out specifically for this project. A total of 2,304 different profiles were obtained for RA, 768 for axSpA, and 3,072 for pSpA. Only 327 (14.2%) patient profiles in RA, 80 (10.4%) in axSpA, and 154 (5%) in pSpA were considered appropriate for reducing the dose of BT. By contrast, 749 (32.5%) patient profiles in RA, 270 (35.3%) in axSpA, and 1,243 (40.5%) in pSpA were considered inappropriate. The remaining profiles were considered uncertain. Appropriateness criteria for reducing the dose of BT were developed in 3 inflammatory conditions. These criteria can help clinicians treating these disorders to optimize the BT dose. However, further research is needed, since more than 50% of the profiles were considered uncertain and the real prevalence of each profile in daily clinical practice remains unknown.

Addition of Aegilops U and M Chromosomes Affects Protein and Dietary Fiber Content of Wholemeal Wheat Flour.

PubMed

Rakszegi, Marianna; Molnár, István; Lovegrove, Alison; Darkó, Éva; Farkas, András; Láng, László; Bedő, Zoltán; Doležel, Jaroslav; Molnár-Láng, Márta; Shewry, Peter

2017-01-01

Cereal grain fiber is an important health-promoting component in the human diet. One option to improve dietary fiber content and composition in wheat is to introduce genes from its wild relatives Aegilops biuncialis and Aegilops geniculata . This study showed that the addition of chromosomes 2U g , 4U g , 5U g , 7U g , 2M g , 5M g , and 7M g of Ae. geniculata and 3U b , 2M b , 3M b , and 7M b of Ae. biuncialis into bread wheat increased the seed protein content. Chromosomes 1U g and 1M g increased the proportion of polymeric glutenin proteins, while the addition of chromosomes 1U b and 6U b led to its decrease. Both Aegilops species had higher proportions of β-glucan compared to arabinoxylan (AX) than wheat lines, and elevated β-glucan content was also observed in wheat chromosome addition lines 5U, 7U, and 7M. The AX content in wheat was increased by the addition of chromosomes 5U g , 7U g , and 1U b while water-soluble AX was increased by the addition of chromosomes 5U, 5M, and 7M, and to a lesser extent by chromosomes 3, 4, 6U g , and 2M b . Chromosomes 5U g and 7M b also affected the structure of wheat AX, as shown by the pattern of oligosaccharides released by digestion with endoxylanase. These results will help to map genomic regions responsible for edible fiber content in Aegilops and will contribute to the efficient transfer of wild alleles in introgression breeding programs to obtain wheat varieties with improved health benefits. Key Message: Addition of Aegilops U- and M-genome chromosomes 5 and 7 improves seed protein and fiber content and composition in wheat.

The autotaxin-LPA2 GPCR axis is modulated by γ-irradiation and facilitates DNA damage repair.

PubMed

Balogh, Andrea; Shimizu, Yoshibumi; Lee, Sue Chin; Norman, Derek D; Gangwar, Ruchika; Bavaria, Mitul; Moon, ChangSuk; Shukla, Pradeep; Rao, Radakrishna; Ray, Ramesh; Naren, Anjaparavanda P; Banerjee, Souvik; Banerje, Souvik; Miller, Duane D; Balazs, Louisa; Pelus, Louis; Tigyi, Gabor

2015-09-01

In this study we characterized the effects of radiation injury on the expression and function of the autotaxin (ATX)-LPA2 GPCR axis. In IEC-6 crypt cells and jejunum enteroids quantitative RT-PCR showed a time- and dose-dependent upregulation of lpa2 in response to γ-irradiation that was abolished by mutation of the NF-κB site in the lpa2 promoter or by inhibition of ATM/ATR kinases with CGK-733, suggesting that lpa2 is a DNA damage response gene upregulated by ATM via NF-κB. The resolution kinetics of the DNA damage marker γ-H2AX in LPA-treated IEC-6 cells exposed to γ-irradiation was accelerated compared to vehicle, whereas pharmacological inhibition of LPA2 delayed the resolution of γ-H2AX. In LPA2-reconstituted MEF cells lacking LPA1&3 the levels of γ-H2AX decreased rapidly, whereas in Vector MEF were high and remained sustained. Inhibition of ERK1&2 or PI3K/AKT signaling axis by pertussis toxin or the C311A/C314A/L351A mutation in the C-terminus of LPA2 abrogated the effect of LPA on DNA repair. LPA2 transcripts in Lin(-)Sca-1(+)c-Kit(+) enriched for bone marrow stem cells were 27- and 5-fold higher than in common myeloid or lymphoid progenitors, respectively. Furthermore, after irradiation higher residual γ-H2AX levels were detected in the bone marrow or jejunum of irradiated LPA2-KO mice compared to WT mice. We found that γ-irradiation increases plasma ATX activity and LPA level that is in part due to the previously established radiation-induced upregulation of TNFα. These findings identify ATX and LPA2 as radiation-regulated genes that appear to play a physiological role in DNA repair. Copyright © 2015. Published by Elsevier Inc.

Edge detection and mathematic fitting for corneal surface with Matlab software.

PubMed

Di, Yue; Li, Mei-Yan; Qiao, Tong; Lu, Na

2017-01-01

To select the optimal edge detection methods to identify the corneal surface, and compare three fitting curve equations with Matlab software. Fifteen subjects were recruited. The corneal images from optical coherence tomography (OCT) were imported into Matlab software. Five edge detection methods (Canny, Log, Prewitt, Roberts, Sobel) were used to identify the corneal surface. Then two manual identifying methods (ginput and getpts) were applied to identify the edge coordinates respectively. The differences among these methods were compared. Binomial curve (y=Ax 2 +Bx+C), Polynomial curve [p(x)=p1x n +p2x n-1 +....+pnx+pn+1] and Conic section (Ax 2 +Bxy+Cy 2 +Dx+Ey+F=0) were used for curve fitting the corneal surface respectively. The relative merits among three fitting curves were analyzed. Finally, the eccentricity (e) obtained by corneal topography and conic section were compared with paired t -test. Five edge detection algorithms all had continuous coordinates which indicated the edge of the corneal surface. The ordinates of manual identifying were close to the inside of the actual edges. Binomial curve was greatly affected by tilt angle. Polynomial curve was lack of geometrical properties and unstable. Conic section could calculate the tilted symmetry axis, eccentricity, circle center, etc . There were no significant differences between 'e' values by corneal topography and conic section ( t =0.9143, P =0.3760 >0.05). It is feasible to simulate the corneal surface with mathematical curve with Matlab software. Edge detection has better repeatability and higher efficiency. The manual identifying approach is an indispensable complement for detection. Polynomial and conic section are both the alternative methods for corneal curve fitting. Conic curve was the optimal choice based on the specific geometrical properties.

MAP kinase-signaling controls nuclear translocation of tripeptidyl-peptidase II in response to DNA damage and oxidative stress

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

Preta, Giulio; Klark, Rainier de; Chakraborti, Shankhamala

2010-08-27

Research highlights: {yields} Nuclear translocation of TPPII occurs in response to different DNA damage inducers. {yields} Nuclear accumulation of TPPII is linked to ROS and anti-oxidant enzyme levels. {yields} MAPKs control nuclear accumulation of TPPII. {yields} Inhibited nuclear accumulation of TPPII decreases DNA damage-induced {gamma}-H2AX expression. -- Abstract: Reactive oxygen species (ROS) are a continuous hazard in eukaroytic cells by their ability to cause damage to biomolecules, in particular to DNA. Previous data indicated that the cytosolic serine peptidase tripeptidyl-peptidase II (TPPII) translocates into the nucleus of most tumor cell lines in response to {gamma}-irradiation and ROS production; an eventmore » that promoted p53 expression as well as caspase-activation. We here observed that nuclear translocation of TPPII was dependent on signaling by MAP kinases, including p38MAPK. Further, this was caused by several types of DNA-damaging drugs, a DNA cross-linker (cisplatinum), an inhibitor of topoisomerase II (etoposide), and to some extent also by nucleoside-analogues (5-fluorouracil, hydroxyurea). In the minority of tumor cell lines where TPPII was not translocated into the nucleus in response to DNA damage we observed reduced intracellular ROS levels, and the expression levels of redox defense systems were increased. Further, treatment with the ROS-inducer {gamma}-hexa-chloro-cyclohexane ({gamma}-HCH, lindane), an inhibitor of GAP junctions, restored nuclear translocation of TPPII in these cell lines upon {gamma}-irradiation. Moreover, blocking nuclear translocation of TPPII in etoposide-treated cells, by using a peptide-derived inhibitor (Z-Gly-Leu-Ala-OH), attenuated expression of {gamma}-H2AX in {gamma}-irradiated melanoma cells. Our results indicated a role for TPPII in MAPK-dependent DNA damage signaling.« less

Conformational preferences for some 3-(4‧-substituted phenylsulfonyl)-1-methyl-2-piperidones through spectroscopic and theoretical studies

NASA Astrophysics Data System (ADS)

Olivato, Paulo R.; Santos, Jean M. M.; Cerqueira, Carlos R.; Vinhato, Elisângela; Zukerman-Schpector, Julio; Ng, Seik Weng; Tiekink, Edward R. T.; Colle, Maurizio Dal

2012-11-01

The analysis of the infrared (IR) carbonyl band of some 3-(4'-substituted phenylsulfonyl)-1-methyl-2-piperidones 1-5 bearing as substituents: OMe 1, Me 2, H 3, Cl 4 and NO25, supported by B3LYP/6-31G(d,p) calculations along with NBO analysis (for 1, 3 and 5) and X-ray diffraction (for 5), indicated the existence of three stable conformations i.e. quasi-axial (q-ax), syn-clinal (s-cl) and quasi-equatorial (q-eq). In the gas phase, the q-ax conformer is calculated as the most stable (ca. 88%) and the least polar, the s-cl conformer is less stable (ca. 12%) but more polar, and the q-eq conformer is the least stable (ca. 1%) and the most polar of the three conformers evaluated. The sum of the most important orbital interactions from NBO analysis and the trend of the electrostatic interactions accounts for the relative populations as well as for the νCO frequencies of the q-ax, s-cl and q-eq conformers calculated in the gas phase. The unique IR νCO band in CCl4 may be ascribed to the most stable q-ax conformer. The more intense (60%) high frequency doublet component in CHCl3 may be assigned to the summing up of the least stable q-eq and the less stable s-cl conformers, as their frequencies are almost coincident. The occurrence of only a single νCO band in both CH2Cl2 and CH3CN supports the fact that the νCO band of the two more polar conformers appear as a single band. Additional support to this rationalization is given by the single point PCM method, which showed a progressive increase of the q-eq + s-cl/q-ax population ratio going from the gas phase to CCl4, to CHCl3, to CH2Cl2 and to CH3CN. X-ray single crystal analysis of 5 indicates that this compound displays a quasi-axial geometry with respect to the [Odbnd Csbnd CHsbnd S] moiety, and that the 2-piperidone ring assumes a slightly distorted half-chair conformation. In the crystal packing, molecules of 5 are arranged into supramolecular layers linked through Csbnd H⋯O interactions along with π⋯π interactions between adjacent benzene rings.

FIRE_AX_SOF_SUR_MET

Atmospheric Science Data Center

2015-11-25

... Buoy Instrument:  Barometer Sonic Anemometer Thermistor Spatial Coverage:  (34.60, ... Earthdata Search Parameters:  Dry Bulb Temperature Pressure Sea Surface Temperature Wet Bulb Temperature ...

FIRE_AX_UW_DSCRT

Atmospheric Science Data Center

2015-11-25

... Analyzer IR CO2 Analyzer Optical Counter Platinum Resistance Spectrometer Spatial Coverage:  (32.34, ... Diameter Particle Number Concentration Potential Temperature Sulfate Sulfur Dioxide Temperature Order Data:  ...

FIRE_AX_PSU_MALBAL

Atmospheric Science Data Center

2015-11-24

... Parameters:  Clouds Irradiance Latent Heat Flux Liquid Water Content Precipitation Rate Sea Surface ... Solar Transmittance Specific Humidity Surface Stress System Optical Depth Temperature Wind Direction Wind Speed ...

AX-5 space suit bearing torque investigation

NASA Technical Reports Server (NTRS)

Loewenthal, Stuart; Vykukal, Vic; Mackendrick, Robert; Culbertson, Philip, Jr.

1990-01-01

The symptoms and eventual resolution of a torque increase problem occurring with ball bearings in the joints of the AX-5 space suit are described. Starting torques that rose 5 to 10 times initial levels were observed in crew evaluation tests of the suit in a zero-g water tank. This bearing problem was identified as a blocking torque anomaly, observed previously in oscillatory gimbal bearings. A large matrix of lubricants, ball separator designs and materials were evaluated. None of these combinations showed sufficient tolerance to lubricant washout when repeatedly cycled in water. The problem was resolved by retrofitting a pressure compensated, water exclusion seal to the outboard side of the bearing cavity. The symptoms and possible remedies to blocking are discussed.

Blocking of conditioned taste avoidance induced by wheel running.

PubMed

Pierce, W David; Heth, C Donald

2010-01-01

In Experiment 1, compared to non-reinforced presentation of a food stimulus (A-->no US), the association of a food stimulus with wheel running (A-->US) blocked subsequent avoidance of a distinctive flavor (X), when both the food and flavor were followed by wheel running (AX-->US). Experiment 2 replicated and extended the blocking effect, demonstrating that the amount of avoidance of X after AX-->wheel training depended on the correlation between A-alone trials and wheel running-the predictiveness of the A stimulus. The present study is the first to demonstrate associative blocking of conditioned taste avoidance (CTA) induced by wheel running and strongly implicates associative learning as the basis for this kind of avoidance. 2009 Elsevier B.V. All rights reserved.

FIRE_AX_UW_C131A

Atmospheric Science Data Center

2015-11-25

... Hot-Wire Hygrometer RMS Pressure Var Platinum Resistance Pyranometer Radiometer Reverse Flow Spatial ... Parameters:  Condensation Nuclei Dew/Frost Point Temperature Droplet Concentration Humidity Irradiance Liquid Water ...

INTEGRAL, XMM-Newton and ESO/NTT identification of AX J1749.1-2733: an obscured and probably distant Be/X-ray binary

NASA Astrophysics Data System (ADS)

Zurita Heras, J. A.; Chaty, S.

2008-10-01

Context: AX J1749.1-2733 is an unclassified transient X-ray source discovered during surveys by ASCA in 1993-1999. The transient behaviour and the short and bright flares of the source have led to the idea that it is part of the recently revealed subclass of supergiant fast X-ray transients. Aims: A multi-wavelength study in NIR, optical, X-rays, and hard X-rays of AX J1749.1-2733 is undertaken in order to determine its nature. Methods: Public INTEGRAL data and our target of opportunity observation with XMM-Newton were used to study the high-energy source through timing and spectral analysis. Multi-wavelength observations in optical and NIR with the ESO/NTT telescope were also performed to search for the counterpart. Results: AX J1749.1-2733 is a new high-mass X-ray binary pulsar with an orbital period of 185.5±1.1 days (or 185.5/f with f=2,3 or 4) and a spin period of 66 s, parameters typical of a Be/X-ray binary. The outbursts last 12 d. A spin-down of dot{P}=0.08 ± 0.02 s yr -1 is also observed, very likely due to the propeller effect. The most accurate X-ray position is RA (2000) =17h49m06.8s and Dec =-27°32 arcmin32.5 arcsec (uncertainty 2 arcsec). The high-energy broad-band spectrum is well-fitted with an absorbed powerlaw and a high-energy cutoff with values NH=20.1-1.3+1.5×1022 cm-2, Γ=1.0-0.3+0.1, and Ecut=21-3+5 keV. The only optical/NIR candidate counterpart within the X-ray error circle has magnitudes of R=21.9±0.1, I=20.92±0.09, J=17.42±0.03, H=16.71±0.02, and Ks=15.75±0.07, which points towards a Be star located far away (>8.5 kpc) and highly absorbed (NH˜ 1.7×1022 cm-2). The average 22-50 keV luminosity is 0.4-0.9×1036 erg s-1 during the long outbursts and 3×1036 erg s-1 during the bright flare that occurred on MJD 52891 for an assumed distance of 8.5 kpc. Based on observations made with 1) INTEGRAL, an ESA project with instruments and science data centre funded by ESA member states (especially the PI countries: Denmark, France, Germany, Italy, Switzerland, Spain), Czech Republic and Poland, and with the participation of Russia and the USA; 2) XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States and NASA; and 3) ESO Telescopes at the La Silla or Paranal Observatories under programme ID 079.D-0432(A).

In Vivo Corrosion of Two Novel Magnesium Alloys ZEK100 and AX30 and Their Mechanical Suitability as Biodegradable Implants

PubMed Central

Huehnerschulte, Tim Andreas; Angrisani, Nina; Rittershaus, Dina; Bormann, Dirk; Windhagen, Henning; Meyer-Lindenberg, Andrea

2011-01-01

In magnesium alloys, the components used modify the alloy properties. For magnesium implants in contact with bone, rare earths alloys are commonly examined. These were shown to have a higher corrosion resistance than other alloys and a high mechanical strength, but their exact composition is hard to predict. Therefore a reduction of their content could be favorable. The alloys ZEK100 and AX30 have a reduced content or contain no rare earths at all. The aim of the study was to investigate their in vivo degradation and to assess the suitability of the in vivo µCT for the examination of their corrosion. Implants were inserted in rabbit tibiae. Clinical examinations, X-rays and in vivo µCT scans were done regularly. Afterwards implants were analyzed with REM, electron dispersive X-ray (EDX), weighing and mechanical testing. The in vivo µCT is of great advantage, because it allows a quantification of the corrosion rate and qualitative 3D assessment of the corrosion morphology. The location of the implant has a remarkable effect on the corrosion rate. Due to its mechanical characteristics and its corrosion behavior, ZEK100 was judged to be suitable, while AX30, which displays favorable degradation behavior, has too little mechanical strength for applications in weight bearing bones. PMID:28879972

Biochemical Kinetics Model of DSB Repair and GammaH2AX FOCI by Non-homologous End Joining

NASA Technical Reports Server (NTRS)

Cucinotta, Francis, A.; Pluth, Janice M.; Anderson, Jennifer A.; Harper, Jane V.; O'Neill, Peter

2007-01-01

We developed a biochemical kinetics approach to describe the repair of double strand breaks (DSB) produced by low LET radiation by modeling molecular events associated with the mechanisms of non-homologous end-joining (NHEJ). A system of coupled non-linear ordinary differential equations describes the induction of DSB and activation pathways for major NHEJ components including Ku(sub 70/80), DNA-PK(sub cs), and the Ligase IV-XRCC4 hetero-dimer. The autophosphorylation of DNA-PK(sub cs and subsequent induction of gamma-H2AX foci observed after ionizing radiation exposure were modeled. A two-step model of DNA-PK(sub cs) regulation of repair was developed with the initial step allowing access of other NHEJ components to breaks, and a second step limiting access to Ligase IV-XRCC4. Our model assumes that the transition from the first to second-step depends on DSB complexity, with a much slower-rate for complex DSB. The model faithfully reproduced several experimental data sets, including DSB rejoining as measured by pulsed-field electrophoresis (PFGE), quantification of the induction of gamma-H2AX foci, and live cell imaging of the induction of Ku(sub 70/80). Predictions are made for the behaviors of NHEJ components at low doses and dose-rates, where a steady-state is found at dose-rates of 0.1 Gy/hr or lower.

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

Martin, Olga A.; Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC; The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC

Purpose: To determine whether radiation therapy (RT) could mobilize viable tumor cells into the circulation of non-small cell lung cancer (NSCLC) patients. Methods and Materials: We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood samples immunostained with conventional CTC markers. We measured their DNA damage levels using γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated cell sorting or by immunofluorescence microscopy. Results: Twenty-seven RT-treated NSCLC patients had blood samples analyzed by 1 or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and inmore » 4 of 8 patients treated with curative-intent RT. Circulating tumor cells were also identified, singly and in clumps in large numbers, during RT by cytopathologic examination (in all 5 cases studied). Elevated γ-H2AX signal in post-RT blood samples signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in vitro (in all 6 cases studied). Circulating tumor cells formed γ-H2AX foci in response to ex vivo irradiation, providing further evidence of their viability. Conclusions: Our findings provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by coadministering systemic therapies.« less

Qiang-Dong proper quantization rule and its applications to exactly solvable quantum systems

NASA Astrophysics Data System (ADS)

Serrano, F. A.; Gu, Xiao-Yan; Dong, Shi-Hai

2010-08-01

We propose proper quantization rule, ∫x_Ax_B k(x)dx-∫x0Ax0Bk0(x)dx=nπ, where k(x )=√2M[E -V(x)] /ℏ. The xA and xB are two turning points determined by E =V(x), and n is the number of the nodes of wave function ψ(x ). We carry out the exact solutions of solvable quantum systems by this rule and find that the energy spectra of solvable systems can be determined only from its ground state energy. The previous complicated and tedious integral calculations involved in exact quantization rule are greatly simplified. The beauty and simplicity of the rule come from its meaning—whenever the number of the nodes of ϕ(x ) or the number of the nodes of the wave function ψ(x ) increases by 1, the momentum integral ∫xAxBk(x )dx will increase by π. We apply this proper quantization rule to carry out solvable quantum systems such as the one-dimensional harmonic oscillator, the Morse potential and its generalization, the Hulthén potential, the Scarf II potential, the asymmetric trigonometric Rosen-Morse potential, the Pöschl-Teller type potentials, the Rosen-Morse potential, the Eckart potential, the harmonic oscillator in three dimensions, the hydrogen atom, and the Manning-Rosen potential in D dimensions.

Effects of linguistic experience on early levels of perceptual tone processing

NASA Astrophysics Data System (ADS)

Huang, Tsan; Johnson, Keith

2005-04-01

This study investigated the phenomenon of language-specificity in Mandarin Chinese tone perception. The main question was whether linguistic experience affects the earliest levels of perceptual processing of tones. Chinese and American English listeners participated in four perception experiments, which involved short inter-stimulus intervals (300 ms or 100 ms) and an AX discrimination or AX degree-of-difference rating task. Three experiments used natural speech monosyllabic tone stimuli and one experiment used time-varying sinusoidal simulations of Mandarin tones. AE listeners showed psychoacoustic listening in all experiments, paying much attention to onset and offset pitch. Chinese listeners showed language-specific patterns in all experiments to various degrees, where tonal neutralization rules reduced perceptual distance between two otherwise contrastive tones for Chinese listeners. Since these experiments employed procedures hypothesized to tap the auditory trace mode (Pisoni, Percept. Psychophys. 13, 253-260 (1973)], language-specificity found in this study seems to support the proposal of an auditory cortical map [Guenther et al., J. Acoust. Soc. Am. 23, 213-221 (1999)]. But the model needs refining to account for different degrees of language-specificity, which are better handled by Johnsons (2004, TLS03:26-41) lexical distance model, although the latter model is too rigid in assuming that linguistic experience does not affect low-level perceptual tasks such as AX discrimination with short ISIs.

White matter changes in preclinical Alzheimer's disease: a magnetic resonance imaging-diffusion tensor imaging study on cognitively normal older people with positive amyloid β protein 42 levels.

PubMed

Molinuevo, José Luis; Ripolles, Pablo; Simó, Marta; Lladó, Albert; Olives, Jaume; Balasa, Mircea; Antonell, Anna; Rodriguez-Fornells, Antoni; Rami, Lorena

2014-12-01

The aim of this study was to use diffusion tensor imaging measures to determine the existence of white matter microstructural differences in the preclinical phases of Alzheimer's disease, assessing cognitively normal older individuals with positive amyloid β protein (Aβ42) levels (CN_Aβ42+) on the basis of normal cognition and cerebrospinal fluid Aβ42 levels below 500 pg/mL. Nineteen CN_Aβ42+ and 19 subjects with Aβ42 levels above 500 pg/mL (CN_Aβ42-) were included. We encountered increases in axial diffusivity (AxD) in CN_Aβ42+ relative to CN_Aβ42- in the corpus callosum, corona radiata, internal capsule, and superior longitudinal fasciculus bilaterally, and also in the left fornix, left uncinate fasciculus, and left inferior fronto-occipital fasciculus. However, no differences were found in other diffusion tensor imaging indexes. Cognitive reserve scores were positively associated with AxD exclusively in the CN_Aβ42+ group. The finding of AxD alteration together with preserved fractional anisotropy, mean diffusivity, and radial diffusivity indexes in the CN_Aβ42+ group may indicate that, subtle axonal changes may be happening in the preclinical phases of Alzheimer's disease, whereas white matter integrity is still widely preserved. Copyright © 2014 Elsevier Inc. All rights reserved.

CARFILZOMIB INTERACTS SYNERGISTICALY WITH HISTONE DEACETYLASE INHIBITORS IN MANTLE CELL LYMPHOMA CELLS IN VITRO AND IN VIVO

PubMed Central

Dasmahapatra, Girija; Lembersky, Dmitry; Son, Minkyeong P.; Attkisson, Elisa; Dent, Paul; Fisher, Richard. I.; Friedberg, Jonathan W.; Grant, Steven

2011-01-01

Interactions between the proteasome inhibitor carfilzomib and the HDAC inhibitors vorinostat and SNDX-275 were examined in mantle cell lymphoma (MCL) cells in vitro and in vivo. Co-administration of very low, marginally toxic carfilzomib concentrations (e.g., 3–4 nM) with minimally lethal vorinostat or SNDX-275 concentrations induced sharp increases in mitochondrial injury and apoptosis in multiple MCL cell lines and primary MCL cells. Enhanced lethalitly was associated with JNK1/2 activation, increased DNA damage (induction of λH2A.X), and ERK1/2 and AKT1/2 inactivation. Co-administration of carfilzomib and HDACIs induced a marked increase in ROS generation, and G2M arrest. Significantly, the free radical scavenger TBAP blocked carfilzomib/HDACI-mediated ROS generation, λH2A.X formation, JNK1/2 activation, and lethality. Genetic (shRNA) knock down of JNK1/2 significantly attenuated carfilzomib/HDACI-induced apoptosis, but did not prevent ROS generation or DNA damage. Carfilzomib/HDACI regimens were also active against bortezomib-resistant MCL cells. Finally, carfilzomib/vorinostat co-administrationo resulted in a pronounced reduction in tumor growth compared to single agent treatment in a MCL xenograft model associated with enhanced apoptosis, λH2A.X formation, and JNK activation. Collectively, these findings suggest that carfilzomib/HDACI regimens warrants attention in MCL. PMID:21750224

Activation of DNA damage repair pathways by murine polyomavirus

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

Heiser, Katie; Nicholas, Catherine; Garcea, Robert

Nuclear replication of DNA viruses activates DNA damage repair (DDR) pathways, which are thought to detect and inhibit viral replication. However, many DNA viruses also depend on these pathways in order to optimally replicate their genomes. We investigated the relationship between murine polyomavirus (MuPyV) and components of DDR signaling pathways including CHK1, CHK2, H2AX, ATR, and DNAPK. We found that recruitment and retention of DDR proteins at viral replication centers was independent of H2AX, as well as the viral small and middle T-antigens. Additionally, infectious virus production required ATR kinase activity, but was independent of CHK1, CHK2, or DNAPK signaling.more » ATR inhibition did not reduce the total amount of viral DNA accumulated, but affected the amount of virus produced, indicating a defect in virus assembly. These results suggest that MuPyV may utilize a subset of DDR proteins or non-canonical DDR signaling pathways in order to efficiently replicate and assemble. -- Highlights: •Murine polyomavirus activates and recruits DNA damage repair (DDR) proteins to replication centers. •Large T-antigen mediates recruitment of DDR proteins to viral replication centers. •Inhibition or knockout of CHK1, CHK2, DNA-PK or H2AX do not affect viral titers. •Inhibition of ATR activity reduces viral titers, but not viral DNA accumulation.« less

Advantage of impulse oscillometry over spirometry to diagnose chronic obstructive pulmonary disease and monitor pulmonary responses to bronchodilators: An observational study.

PubMed

Saadeh, Constantine; Saadeh, Charles; Cross, Blake; Gaylor, Michael; Griffith, Melissa

2015-01-01

This retrospective study was a comparative analysis of sensitivity of impulse oscillometry and spirometry techniques for use in a mixed chronic obstructive pulmonary disease group for assessing disease severity and inhalation therapy. A total of 30 patients with mild-to-moderate chronic obstructive pulmonary disease were monitored by impulse oscillometry, followed by spirometry. Lung function was measured at baseline after bronchodilation and at follow-up (3-18 months). The impulse oscillometry parameters were resistance in the small and large airways at 5 Hz (R5), resistance in the large airways at 15 Hz (R15), and lung reactance (area under the curve X; AX). After the bronchodilator therapy, forced expiratory volume in 1 second (FEV1) readings evaluated by spirometry were unaffected at baseline and at follow-up, while impulse oscillometry detected an immediate improvement in lung function, in terms of AX (p = 0.043). All impulse oscillometry parameters significantly improved at follow-up, with a decrease in AX by 37% (p = 0.0008), R5 by 20% (p = 0.0011), and R15 by 12% (p = 0.0097). Impulse oscillometry parameters demonstrated greater sensitivity compared with spirometry for monitoring reversibility of airway obstruction and the effect of maintenance therapy. Impulse oscillometry may facilitate early treatment dose optimization and personalized medicine for chronic obstructive pulmonary disease patients.

Blood, sweat and semen: the economy of axé and the response of Afro-Brazilian religions to HIV and AIDS in Recife.

PubMed

Rios, Luis Felipe; Oliveira, Cinthia; Garcia, Jonathan; Muñoz-Laboy, Miguel; Murray, Laura; Parker, Richard

2011-01-01

This article provides an ethnographic analysis of Afro-Brazilian religious responses to the HIV epidemic in Recife. Drawing on participant observation and in-depth interviews conducted with Afro-Brazilian religious leaders and public health officials, it highlights the importance of the axé--a mystical energy manipulated in religious rituals that is symbolically associated with blood, sweat and semen. In an analysis of the relationship formed between the state AIDS programme and Afro-Brazilian religious centres, we conclude that the recognition of native categories and their meanings is one of the key elements to a fruitful dialogue between public health programmes and religious leaders that in the case studied, resulted in the re-signification of cultural practices to prevent HIV. Although the Afro-Brazilian religious leaders interviewed tended to be more open about sexuality and condom promotion, stigma towards people living with HIV (PLHIV) was still present within the religious temples, yet appeared to be more centred upon the perception of HIV as negatively affecting followers' axé than judgement related to how one may have contracted the virus. We discuss the tensions between taking a more liberal and open stance on prevention, while also fostering attitudes that may stigmatise PLHIV, and make suggestions for improving the current Afro-Brazilian response to the epidemic.

Localized CT-Guided Irradiation Inhibits Neurogenesis in Specific Regions of the Adult Mouse Brain

PubMed Central

Ford, E. C.; Achanta, P.; Purger, D.; Armour, M.; Reyes, J.; Fong, J.; Kleinberg, L.; Redmond, K.; Wong, J.; Jang, M. H.; Jun, H.; Song, H-J.; Quinones-Hinojosa, A.

2011-01-01

Radiation is used in the study of neurogenesis in the adult mouse both as a model for patients undergoing radiation therapy for CNS malignancies and as a tool to interrupt neurogenesis. We describe the use of a dedicated CT-guided precision device to irradiate specific sub-regions of the adult mouse brain. Improved CT visualization was accomplished with intrathecal injection of iodinated contrast agent, which enhances the lateral ventricles. T2-weighted MRI images were also used for target localization. Visualization of delivered beams (10 Gy) in tissue was accomplished with immunohistochemical staining for the protein γ-H2AX, a marker of DNA double-strand breaks. γ-H2AX stains showed that the lateral ventricle wall could be targeted with an accuracy of 0.19 mm (n = 10). In the hippocampus, γ-H2AX staining showed that the dentate gyrus can be irradiated unilaterally with a localized arc treatment. This resulted in a significant decrease of proliferative neural progenitor cells as measured by Ki-67 staining (P < 0.001) while leaving the contralateral side intact. Two months after localized irradiation, neurogenesis was significantly inhibited in the irradiated region as seen with EdU/NeuN double labeling (P < 0.001). Localized radiation in the rodent brain is a promising new tool for the study of neurogenesis. PMID:21449714

Blood, sweat and semen: The economy of axé and the response of Afro-Brazilian religions to HIV and AIDS in Recife

PubMed Central

Rios, Luis Felipe; Oliveira, Cinthia; Garcia, Jonathan; Muñoz-Laboy, Miguel; Murray, Laura; Parker, Richard

2011-01-01

This article provides an ethnographic analysis of Afro-Brazilian religious responses to the HIV epidemic in Recife. Drawing on participant observation and in-depth interviews conducted with Afro-Brazilian religious leaders and public health officials, it highlights the importance of the axé – a mystical energy manipulated in religious rituals that is symbolically associated with blood, sweat, and semen. In an analysis of the relationship formed between the state AIDS programme and Afro-Brazilian religious centres, we conclude that the recognition of native categories and their meanings is one of the key elements to a fruitful dialogue between public health programmes and religious leaders that in the case studied, resulted in the re-signification of cultural practices to prevent HIV. Although the Afro-Brazilian religious leaders interviewed tended to be more open about sexuality and condom promotion, stigma towards people living with HIV (PLHIV) was still present within the religious temples, yet appeared to be more centred upon the perception of HIV as negatively affecting followers’ axé than judgment related to how one may have contracted the virus. We discuss the tensions between taking a more liberal and open stance on prevention, while also fostering attitudes that may stigmatise PLHIV, and make suggestions for improving the current Afro-Brazilian response to the epidemic. PMID:21830866

53BP1 loss suppresses the radiosensitizing effect of icotinib hydrochloride in colorectal cancer cells.

PubMed

Huang, Ai; Yao, Jing; Liu, Tao; Lin, Zhenyu; Zhang, Sheng; Zhang, Tao; Ma, Hong

2018-04-01

This study aimed to investigate the influence of the expression of P53-binding protein 1 (53BP1), a key component in DNA damage repair pathways, on the radiosensitizing effect of icotinib hydrochloride in colorectal cancer and to elucidate the mechanisms underlying this influence. Real-time RT-PCR and Western blotting were performed to verify the gene-knockout effect of 53BP1 small hairpin RNA (ShRNA), and colony formation assay was employed to investigate the influence of 53BP1 downregulation on the radiosensitizing effect of icotinib hydrochloride in HCT116 cells. Cell apoptosis, cell cycle distributions, and histone H2AX (γ-H2AX) fluorescence foci after 53BP1 knockdown were evaluated. Relative protein expression in the ataxia telangiectasia mutated kinase (ATM)-checkpoint kinase-2 (CHK2)-P53 pathway was measured by Western blot analysis to unravel the molecular mechanisms linking the pathway to the above phenomena. Icotinib hydrochloride increased the radiosensitivity of HCT116 cells; however, this effect was suppressed by the downregulation of 53BP1 expression, a change that inhibited cell apoptosis, increased the percentage of HCT116 cells arrested in S-phase and inhibited the protein expression of key molecules in the ATM-CHK2-P53 apoptotic pathway. Our studies confirmed that the loss of 53BP1 serves as a negative regulator of the radiosensitizing effect of icotinib in part by suppressing the ATM-CHK2-P53 apoptotic pathway.

Human cytomegalovirus UL76 induces chromosome aberrations

PubMed Central

2009-01-01

Background Human cytomegalovirus (HCMV) is known to induce chromosome aberrations in infected cells, which can lead to congenital abnormalities in infected fetuses. HCMV UL76 belongs to a conserved protein family from herpesviruses. Some reported roles among UL76 family members include involvement in virulence determination, lytic replication, reactivation of latent virus, modulation of gene expression, induction of apoptosis, and perturbation of cell cycle progression, as well as potential nuclease activity. Previously, we have shown that stable expression of UL76 inhibits HCMV replication in glioblastoma cells. Methods To examine chromosomal integrity and the DNA damage signal γ-H2AX in cells constitutively expressing UL76, immunofluorescent cell staining and Western blotting were performed. The comet assay was employed to assess DNA breaks in cells transiently expressing UL76. Results We report that stably transfected cells expressing UL76 developed chromosome aberrations including micronuclei and misaligned chromosomes, lagging and bridging. In mitotic cells expressing UL76, aberrant spindles were increased compared to control cells. However, cells with supernumerary centrosomes were marginally increased in UL76-expressing cells relative to control cells. We further demonstrated that UL76-expressing cells activated the DNA damage signal γ-H2AX and caused foci formation in nuclei. In addition, the number of cells with DNA breaks increased in proportion to UL76 protein levels. Conclusion Our findings suggest that the virus-associated protein UL76 induces DNA damage and the accumulation of chromosome aberrations. PMID:19930723

FIRE_AX_UKMO_C130

Atmospheric Science Data Center

2015-11-25

... FSSP Gust Probe Hot-Wire Hygrometer Platinum Resistance PMS 2D-C Probe PRT-4 Pyranometer Pyrgeometer ... Parameters:  Barometric Altitude Cloud Top Temperature Deiced Temperature Dew/Frost Point Temperature Droplet ...

Computation of eigenpairs of Ax = lambda Bx for vibrations of spinning deformable bodies

NASA Technical Reports Server (NTRS)

Utku, S.; Clemente, J. L. M.

1984-01-01

It is shown that, when linear theory is used, the general eigenvalue problem related with the free vibrations of spinning deformable bodies is of the type AX = lambda Bx, where A is Hermitian, and B is real positive definite. Since the order n of the matrices may be large, and A and B are banded or block banded, due to the economics of the numerical solution, one is interested in obtaining only those eigenvalues which fall within the frequency band of interest of the problem. The paper extends the well known method of bisections and iteration of R to the n power to n dimensional complex spaces, i.e., to C to the n power, so that it can be applied to the present problem.

An empirical investigation of methods for nonsymmetric linear systems

NASA Technical Reports Server (NTRS)

Sherman, A. H.

1981-01-01

The present investigation is concerned with a comparison of methods for solving linear algebraic systems which arise from finite difference discretizations of the elliptic convection-diffusion equation in a planar region Omega with Dirichlet boundary conditions. Such linear systems are typically of the form Ax = b where A is an N x N sparse nonsymmetric matrix. In a discussion of discretizations, it is assumed that a regular rectilinear mesh of width h has been imposed on Omega. The discretizations considered include central differences, upstream differences, and modified upstream differences. Six methods for solving Ax = b are considered. Three variants of Gaussian elimination have been chosen as representatives of state-of-the-art software for direct methods under different assumptions about pivoting. Three iterative methods are also included.

On the identification of continuous vibrating systems modelled by hyperbolic partial differential equations

NASA Technical Reports Server (NTRS)

Udwadia, F. E.; Garba, J. A.

1983-01-01

This paper deals with the identification of spatially varying parameters in systems of finite spatial extent which can be described by second order hyperbolic differential equations. Two questions have been addressed. The first deals with 'partial identification' and inquires into the possibility of retrieving all the eigenvalues of the system from response data obtained at one location x-asterisk epsilon (0, 1). The second deals with the identification of the distributed coefficients rho(x), a(x) and b(x). Sufficient conditions for unique identification of all the eigenvalues of the system are obtained, and conditions under which the coefficients can be uniquely identified using suitable response data obtained at one point in the spatial domain are determined. Application of the results and their usefulness is demonstrated in the identification of the properties of tall building structural systems subjected to dynamic load environments.

Digital evaluation of the fit of zirconia-reinforced lithium silicate crowns with a new three-dimensional approach.

PubMed

Zimmermann, Moritz; Valcanaia, Andre; Neiva, Gisele; Mehl, Albert; Fasbinder, Dennis

2017-11-30

Several methods for the evaluation of fit of computer-aided design/computer-assisted manufacture (CAD/CAM)-fabricated restorations have been described. In the study, digital models were recorded with an intraoral scanning device and were measured using a new three-dimensional (3D) computer technique to evaluate restoration internal fit. The aim of the study was to evaluate the internal adaptation and fit of chairside CAD/CAM-fabricated zirconia-reinforced lithium silicate ceramic crowns fabricated with different post-milling protocols. The null hypothesis was that different post-milling protocols did not influence the fitting accuracy of zirconia-reinforced lithium silicate restorations. A master all-ceramic crown preparation was completed on a maxillary right first molar on a typodont. Twenty zirconia-reinforced lithium silicate ceramic crowns (Celtra Duo, Dentsply Sirona) were designed and milled using a chairside CAD/CAM system (CEREC Omnicam, Dentsply Sirona). The 20 crowns were randomly divided into two groups based on post-milling protocols: no manipulation after milling (Group MI) and oven fired-glazing after milling (Group FG). A 3D computer method was used to evaluate the internal adaptation of the crowns. This was based on a subtractive analysis of a digital scan of the crown preparation and a digital scan of the thickness of the cement space over the crown preparation as recorded by a polyvinylsiloxane (PVS) impression material. The preparation scan and PVS scan were matched in 3D and a 3D difference analysis was performed with a software program (OraCheck, Cyfex). Three areas of internal adaptation and fit were selected for analysis: margin (MA), axial wall (AX), and occlusal surface (OC). Statistical analysis was performed using 80% percentile and one-way ANOVA with post-hoc Scheffé test (P = .05). The closest internal adaptation of the crowns was measured at the axial wall with 102.0 ± 11.7 µm for group MI-AX and 106.3 ± 29.3 µm for group FG-AX. The largest internal adaptation of the crowns was measured for the occlusal surface with 258.9 ± 39.2 µm for group MI-OC and 260.6 ± 55.0 µm for group FG-OC. No statistically significant differences were found for the post-milling protocols (P > .05). The 3D difference pattern was visually analyzed for each area with a color-coded scheme. Post-milling processing did not affect the internal adaptation of zirconia-reinforced lithium silicate crowns fabricated with a chairside CAD/CAM technique. The new 3D computer technique for the evaluation of fit of restorations may be highly promising and has the opportunity to be applied to clinical studies.

Contrasting cellular damage after Blue-IRIS and Femto-LASIK in cat cornea.

PubMed

Wozniak, Kaitlin T; Elkins, Noah; Brooks, Daniel R; Savage, Daniel E; MacRae, Scott; Ellis, Jonathan D; Knox, Wayne H; Huxlin, Krystel R

2017-12-01

Blue-intra-tissue refractive index shaping (Blue-IRIS) is a new approach to laser refractive correction of optical aberrations in the eye, which alters the refractive index of the cornea rather than changing its shape. Before it can be implemented in humans, it is critical to establish whether and to what extent, Blue-IRIS damages the cornea. Here, we contrasted the impact of -1.5 D cylinder refractive corrections inscribed using either Blue-IRIS or femtosecond laser in-situ keratomileusis (femto-LASIK) on corneal cell viability. Blue-IRIS was used to write a -1.5 D cylinder gradient index (GRIN) lens over a 2.5 mm by 2.5 mm area into the mid-stromal region of the cornea in six freshly-enucleated feline eyes. The same correction (-1.5 D cylinder) was inscribed into another four cat eyes using femto-LASIK. Six hours later, all corneas were processed for histology and stained for terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) and p-γ-H2AX to label damaged cells. In Blue-IRIS-treated corneas, no tissue was removed and TUNEL-stained cells were confined to the laser focal zone in the stroma. In femto-LASIK, photoablation removed 14 μm of anterior stroma, but in addition, TUNEL-positive cells clustered across the femto-flap, the epithelium at the flap edges and the stroma below the ablation zone. Keratocytes positive for p-γ-H2AX were seen adjacent to all Blue-IRIS focal zones, but were completely absent from femto-LASIK-treated corneas. Unlike femto-LASIK, Blue-IRIS attains refractive correction in the cornea without tissue removal and only causes minimal, localized keratocyte death within the laser focal zones. In addition, Blue-IRIS induced DNA modifications associated with phosphorylation of γ-H2AX in keratocytes adjacent to the laser focal zones. We posit that this p-γ-H2AX response is related to alterations in chromatin structure caused by localized changes in osmolarity, a possible mechanism for the induced refractive index changes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gefitinib Radiosensitizes Stem-Like Glioma Cells: Inhibition of Epidermal Growth Factor Receptor-Akt-DNA-PK Signaling, Accompanied by Inhibition of DNA Double-Strand Break Repair

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

Kang, Khong Bee, E-mail: dmskkb@nccs.com.sg; Zhu Congju; Wong Yinling

Purpose: We compared radiosensitivity of brain tumor stem cells (BTSCs) with matched nonstem glioma cells, and determined whether gefitinib enhanced BTSC radiosensitivity by inhibiting epidermal growth factor receptor (EGFR)-Akt-DNA-dependent protein kinase (DNA-PK) signaling, followed by enhanced DNA double-stand breaks (DSBs) and inhibition of DSB repair. Methods and Materials: Radiosensitivity of stem-like gliomaspheres and nonstem glioma cells (obtained at patient neurosurgical resection) were evaluated by clonogenic assays, {gamma}-H{sub 2}AX immunostaining and cell cycle distribution. Survival of irradiated and nonirradiated NOD-SCID mice intracranially implanted with stem-like gliomaspheres were monitored. Glioma cells treated with gefitinib, irradiation, or both were assayed for clonogenic survival,more » {gamma}-H{sub 2}AX immunostaining, DNA-PKcs expression, and phosphorylation of EGFR and Akt. Results: Stem-like gliomaspheres displayed BTSC characteristics of self-renewal; differentiation into lineages of neurons, oligodendrocytes, and astrocytes; and initiation of glioma growth in NOD-SCID mice. Irradiation dose-dependently reduced clonogenic survival, induced G{sub 2}/M arrest and increased {gamma}-H{sub 2}AX immunostaining of nonstem glioma cells, but not stem-like gliomaspheres. There was no difference in survival of irradiated and nonirradiated mice implanted with stem-like gliomaspheres. The addition of gefitinib significantly inhibited clonogenic survival, increased {gamma}-H{sub 2}AX immunostaining, and reduced DNA-PKcs expression of irradiated stem-like gliomaspheres, without affecting irradiated-nonstem glioma cells. Gefitinib alone, and when combined with irradiation, inhibited phosphorylation of EGFR (Y1068 and Y1045) and Akt (S473) in stem-like gliomaspheres. In nonstem glioma cells, gefitinib alone inhibited EGFR Y1068 phosphorylation, with further inhibition by combined gefitinib and irradiation. Conclusions: Stem-like gliomaspheres are resistant to irradiation-induced cytotoxicity, G{sub 2}/M arrest, and DNA DSBs, compared with nonstem glioma cells. Gefitinib differentially enhances radiosensitivity of stem-like gliomaspheres by reducing EGFR-Akt activation and DNA-PKcs expression, accompanied by enhanced irradiation-induced DNA DSBs and inhibition of DSB repair.« less