Assessment of global longitudinal strain using standardized myocardial deformation imaging: a modality independent software approach.

PubMed

Riffel, Johannes H; Keller, Marius G P; Aurich, Matthias; Sander, Yannick; Andre, Florian; Giusca, Sorin; Aus dem Siepen, Fabian; Seitz, Sebastian; Galuschky, Christian; Korosoglou, Grigorios; Mereles, Derliz; Katus, Hugo A; Buss, Sebastian J

2015-07-01

Myocardial deformation measurement is superior to left ventricular ejection fraction in identifying early changes in myocardial contractility and prediction of cardiovascular outcome. The lack of standardization hinders its clinical implementation. The aim of the study is to investigate a novel standardized deformation imaging approach based on the feature tracking algorithm for the assessment of global longitudinal (GLS) and global circumferential strain (GCS) in echocardiography and cardiac magnetic resonance imaging (CMR). 70 subjects undergoing CMR were consecutively investigated with echocardiography within a median time of 30 min. GLS and GCS were analyzed with a post-processing software incorporating the same standardized algorithm for both modalities. Global strain was defined as the relative shortening of the whole endocardial contour length and calculated according to the strain formula. Mean GLS values were -16.2 ± 5.3 and -17.3 ± 5.3 % for echocardiography and CMR, respectively. GLS did not differ significantly between the two imaging modalities, which showed strong correlation (r = 0.86), a small bias (-1.1 %) and narrow 95 % limits of agreement (LOA ± 5.4 %). Mean GCS values were -17.9 ± 6.3 and -24.4 ± 7.8 % for echocardiography and CMR, respectively. GCS was significantly underestimated by echocardiography (p < 0.001). A weaker correlation (r = 0.73), a higher bias (-6.5 %) and wider LOA (± 10.5 %) were observed for GCS. GLS showed a strong correlation (r = 0.92) when image quality was good, while correlation dropped to r = 0.82 with poor acoustic windows in echocardiography. GCS assessment revealed only a strong correlation (r = 0.87) when echocardiographic image quality was good. No significant differences for GLS between two different echocardiographic vendors could be detected. Quantitative assessment of GLS using a standardized software algorithm allows the direct comparison of values acquired irrespective of the imaging modality. GLS may, therefore, serve as a reliable parameter for the assessment of global left ventricular function in clinical routine besides standard evaluation of the ejection fraction.

Fish passage and abundance around grade control structures on incised streams

USGS Publications Warehouse

Thomas, J.T.; Papanicolaou, A.N.; Pierce, C.L.; Dermisis, D.C.; Litvan, M.E.; Larson, C.J.

2009-01-01

This paper summarizes research from separate studies of fish passage over weirs (Larson et al., 2004; Litvan, 2006; Litvan, et al., 2008a-c) and weir hydraulics (Papanicolaou and Dermisis, 2006; Papanicolaou and Dermisis, in press). Channel incision in the deep loess region of western Iowa has caused decreased biodiversity because streams have high sediment loads, altered flow regimes, lost habitat, and lost lateral connectivity with their former floodplains. In-stream grade control structures (GCS) are built to prevent further erosion, protect infrastructure, and reduce sediment loads. However, GCS can have a detrimental impact on fisheries abundance and migration, biodiversity, and longitudinal connectivity. Fish mark-recapture studies were performed on stretches of streams with and without GCS. GCS with vertical or 1:4 (rise/run) downstream slopes did not allow fish migration, but GCS with slopes ??? 1:15 did. GCS sites were characterized by greater proportions of pool habitat, maximum depths, fish biomass, slightly higher index of biotic integrity (IBI) scores, and greater macroinvertebrate abundance and diversity than non-GCS sites. After modification of three GCS, IBI scores increased and fish species exhibiting truncated distributions before were found throughout the study area. Another study examined the hydraulic performance of GCS to facilitate unimpeded fish passage by determining the mean and turbulent flow characteristics in the vicinity of the GCS via detailed, non-intrusive field tests. Mean flow depth (Y) and velocity (V) atop the GCS were critical for evaluating GCS performance. Turbulent flow measurements illustrated that certain GCS designs cause sudden constrictions which form eddies large enough to disorient fish. GCS with slopes ??? 1:15 best met the minimum requirements to allow catfish passage of a flow depth of ??? 0.31 m and a mean flow velocity of ??? 1.22 m/s. ?? 2009 ASCE.

Software framework for automatic learning of telescope operation

NASA Astrophysics Data System (ADS)

Rodríguez, Jose A.; Molgó, Jordi; Guerra, Dailos

2016-07-01

The "Gran Telescopio de Canarias" (GTC) is an optical-infrared 10-meter segmented mirror telescope at the ORM observatory in Canary Islands (Spain). The GTC Control System (GCS) is a distributed object and component oriented system based on RT-CORBA and it is responsible for the operation of the telescope, including its instrumentation. The current development state of GCS is mature and fully operational. On the one hand telescope users as PI's implement the sequences of observing modes of future scientific instruments that will be installed in the telescope and operators, in turn, design their own sequences for maintenance. On the other hand engineers develop new components that provide new functionality required by the system. This great work effort is possible to minimize so that costs are reduced, especially if one considers that software maintenance is the most expensive phase of the software life cycle. Could we design a system that allows the progressive assimilation of sequences of operation and maintenance of the telescope, through an automatic self-programming system, so that it can evolve from one Component oriented organization to a Service oriented organization? One possible way to achieve this is to use mechanisms of learning and knowledge consolidation to reduce to the minimum expression the effort to transform the specifications of the different telescope users to the operational deployments. This article proposes a framework for solving this problem based on the combination of the following tools: data mining, self-Adaptive software, code generation, refactoring based on metrics, Hierarchical Agglomerative Clustering and Service Oriented Architectures.

Effects of grade control structures on the macroinvertebrate assemblage of an agriculturally impacted stream

USGS Publications Warehouse

Litvan, M.E.; Stewart, T.W.; Pierce, C.L.; Larson, C.J.

2008-01-01

Nearly 400 rock rip-rap grade control structures (hereafter GCS) were recently placed in streams of western Iowa, USA to reduce streambank erosion and protect bridge infrastructure and farmland. In this region, streams are characterized by channelized reaches, highly incised banks and silt and sand substrates that normally support low macroinvertebrate abundance and diversity. Therefore, GCS composed of rip-rap provide the majority of coarse substrate habitat for benthic macroinvertebrates in these streams. We sampled 20 sites on Walnut Creek, Montgomery County, Iowa to quantify macroinvertebrate assemblage characteristics (1) on GCS rip-rap and at sites located (2) 5-50 m upstream of GCS, (3) 5-50 m downstream of GCS and (4) at least 1 km from any GCS (five sites each). Macroinvertebrate biomass, numerical densities and diversity were greatest at sites with coarse substrates, including GCS sites and one natural riffle site and relatively low at remaining sites with soft substrates. Densities of macroinvertebrates in the orders Ephemeroptera, Trichoptera, Diptera, Coleoptera and Acariformes were abundant on GCS rip-rap. Increases in macroinvertebrate biomass, density and diversity at GCS may improve local efficiency of breakdown of organic matter and nutrient and energy flow, and provide enhanced food resources for aquatic vertebrates. However, lack of positive macroinvertebrate responses immediately upstream and downstream of GCS suggest that positive effects might be restricted to the small areas of streambed covered by GCS. Improved understanding of GCS effects at both local and ecosystem scales is essential for stream management when these structures are present. Copyright ?? 2007 John Wiley & Sons, Ltd.

A realistic bi-hemispheric model of the cerebellum uncovers the purpose of the abundant granule cells during motor control.

PubMed

Pinzon-Morales, Ruben-Dario; Hirata, Yutaka

2015-01-01

The cerebellar granule cells (GCs) have been proposed to perform lossless, adaptive spatio-temporal coding of incoming sensory/motor information required by downstream cerebellar circuits to support motor learning, motor coordination, and cognition. Here we use a physio-anatomically inspired bi-hemispheric cerebellar neuronal network (biCNN) to selectively enable/disable the output of GCs and evaluate the behavioral and neural consequences during three different control scenarios. The control scenarios are a simple direct current motor (1 degree of freedom: DOF), an unstable two-wheel balancing robot (2 DOFs), and a simulation model of a quadcopter (6 DOFs). Results showed that adequate control was maintained with a relatively small number of GCs (< 200) in all the control scenarios. However, the minimum number of GCs required to successfully govern each control plant increased with their complexity (i.e., DOFs). It was also shown that increasing the number of GCs resulted in higher robustness against changes in the initialization parameters of the biCNN model (i.e., synaptic connections and synaptic weights). Therefore, we suggest that the abundant GCs in the cerebellar cortex provide the computational power during the large repertoire of motor activities and motor plants the cerebellum is involved with, and bring robustness against changes in the cerebellar microcircuit (e.g., neuronal connections).

Effects of grade control structures on fish passage, biological assemblages, and hydraulic environments in western Iowa streams: a multidisciplinary review

USGS Publications Warehouse

Thomas, J.T.; Culler, M.E.; Dermisis, D.C.; Pierce, Clay; Papanicolaou, A.N.; Stewart, T.W.; Larson, C.J.

2011-01-01

Land use changes and channelization of streams in the deep loess region of western Iowa have led to stream channel incision, altered flow regimes, increased sediment inputs, decreased habitat diversity and reduced lateral connectivity of streams and floodplains. Grade control structures (GCSs) are built in streams to prevent further erosion, protect infrastructure and reduce sediment loads. However, GCS can have a detrimental impact on fisheries and biological communities. We review three complementary biological and hydraulic studies on the effects of GCS in these streams. GCS with steep (≥1:4 rise : run) downstream slopes severely limited fish passage, but GCS with gentle slopes (≤1:15) allowed greater passage. Fish assemblages were dominated by species tolerant of degradation, and Index of Biotic Integrity (IBI) scores were indicative of fair or poor biotic integrity. More than 50% of fish species had truncated distributions. After modification of GCS to reduce slopes and permit increased passage, IBI scores increased and several species were detected further upstream than before modification. Total macroinvertebrate density, biomass and taxonomic diversity and abundance of ecologically sensitive taxa were greater at GCS than in reaches immediately upstream, downstream or ≥1 km from GCS. A hydraulic study confirmed results from fish passage studies; minimum depths and maximum current velocities at GCS with gentle slopes (≤1:15) were more likely to meet minimum criteria for catfish passage than GCS with steeper slopes. Multidisciplinary approaches such as ours will increase understanding of GCS-associated factors influencing fish passage, biological assemblage structure and other ecological relationships in streams.

Model mice for mild-form glycine encephalopathy: behavioral and biochemical characterizations and efficacy of antagonists for the glycine binding site of N-methyl D-aspartate receptor.

PubMed

Kojima-ishii, Kanako; Kure, Shigeo; Ichinohe, Akiko; Shinka, Toshikatsu; Narisawa, Ayumi; Komatsuzaki, Shoko; Kanno, Junnko; Kamada, Fumiaki; Aoki, Yoko; Yokoyama, Hiroyuki; Oda, Masaya; Sugawara, Taku; Mizoi, Kazuo; Nakahara, Daiichiro; Matsubara, Yoichi

2008-09-01

Glycine encephalopathy (GE) is caused by an inherited deficiency of the glycine cleavage system (GCS) and characterized by accumulation of glycine in body fluids and various neurologic symptoms. Coma and convulsions develop in neonates in typical GE while psychomotor retardation and behavioral abnormalities in infancy and childhood are observed in mild GE. Recently, we have established a transgenic mouse line (low-GCS) with reduced GCS activity (29% of wild-type (WT) C57BL/6) and accumulation of glycine in the brain (Stroke, 2007; 38:2157). The purpose of the present study is to characterize behavioral features of the low-GCS mouse as a model of mild GE. Two other transgenic mouse lines were also analyzed: high-GCS mice with elevated GCS activity and low-GCS-2 mice with reduced GCS activity. As compared with controls, low-GCS mice manifested increased seizure susceptibility, aggressiveness and anxiety-like activity, which resembled abnormal behaviors reported in mild GE, whereas high-GCS mice were less sensitive to seizures, hypoactive and less anxious. Antagonists for the glycine-binding site of the N-methyl-D-aspartate receptor significantly ameliorated elevated locomotor activity and seizure susceptibility in the low-GCS mice. Our results suggest the usefulness of low-GCS mice as a mouse model for mild GE and a novel therapeutic strategy.

A gamma ray observatory ground attitude error analysis study using the generalized calibration system

NASA Technical Reports Server (NTRS)

Ketchum, E.

1988-01-01

The Goddard Space Flight Center (GSFC) Flight Dynamics Division (FDD) will be responsible for performing ground attitude determination for Gamma Ray Observatory (GRO) support. The study reported in this paper provides the FDD and the GRO project with ground attitude determination error information and illustrates several uses of the Generalized Calibration System (GCS). GCS, an institutional software tool in the FDD, automates the computation of the expected attitude determination uncertainty that a spacecraft will encounter during its mission. The GRO project is particularly interested in the uncertainty in the attitude determination using Sun sensors and a magnetometer when both star trackers are inoperable. In order to examine the expected attitude errors for GRO, a systematic approach was developed including various parametric studies. The approach identifies pertinent parameters and combines them to form a matrix of test runs in GCS. This matrix formed the basis for this study.

Fish assemblages in a western Iowa stream modified by grade control structures

USGS Publications Warehouse

Litvan, M.E.; Pierce, C.L.; Stewart, T.W.; Larson, C.J.

2008-01-01

Over 400 riprap grade control structures (GCSs) have been built in streams of western Iowa to reduce erosion and protect bridges, roads, and farmland. In conjunction with a companion study evaluating fish passage over GCSs in Turkey Creek, we evaluated the differences in fish assemblage and habitat characteristics in reaches immediately downstream from GCSs (GCS sites) and reaches at least 1 km from any GCS (non-GCS sites). The GCS sites were characterized by greater proportions of pool habitat, maximum depths, fish biomass, and abundance of juvenile largemouth bass Micropterus salmoides than were non-GCS sites. Index of biotic integrity (IBI) scores were poor or fair (<43 on a 0-100 scale) and not significantly different between the GCS and non-GCS sites. Additionally, we investigated both the longitudinal changes in fish assemblages in this GCS-fragmented stream and the changes in fish assemblages after slope modifications of three GCSs to facilitate fish passage. Thirteen fish species were present throughout the study area, whereas another 15 species exhibited truncated distributions not extending to the most upstream sampling location. After modification of the GCSs, IBI scores increased at seven of nine sites (mean increase =4.6 points). Also, channel catfish Ictalurus punctatus were detected 7.3 km upstream at sites where, 2 years before GCS modification, they had been absent from collections. Given the number and distribution of GCSs in western Iowa streams, understanding the effects of these structures is vital to the conservation and management of fish assemblages in this and other regions where GCSs or similar structures are used. ?? Copyright by the American Fisheries Society 2008.

Use of parenteral glucocorticoids and the risk of new onset type 2 diabetes mellitus: A case-control study.

PubMed

Keyany, Ala; Nielen, Johannes T H; Souverein, Patrick C; de Vries, Frank; van den Bemt, Bart

2018-05-01

Use of oral glucocorticoids (GCs) has been associated with hyperglycaemia and type 2 diabetes mellitus (T2DM). However, unlike oral GCs, there is minimal or no data on the effect of parenteral GC use on T2DM. To assess the association between use of parenteral GCs and the risk of receiving a first prescription of a non-insulin antidiabetic drug (NIAD) as a proxy for new onset of T2DM. A population based case-control study was performed using the Clinical Practice Research Datalink (CPRD). Cases (n = 177,154) were defined as patients >18 years of age who had their first ever NIAD prescription between January 1987 and October 2013. Controls were matched by age, gender and general practitioner practice. Conditional logistic regression analyses were used to estimate the risk of NIAD prescription and use of parenteral GCs. Our analyses were statistically adjusted for lifestyle factors, comorbidities and concomitant drug use. Although this study confirmed that oral GCs increases the risk of receiving a first prescription of a NIAD (OR 2.63 [95% CI 2.53-2.73]), there was no association between the use of parenterally administered GCs and the risk of receiving a first prescription of a NIAD (OR 0.88 [95% CI 0.76-1.02]). The number of GC prescriptions was not associated with risk of new onset T2DM compared to no parenteral GCs use; neither the type of GC. Our study does not demonstrate an association between the use of parenteral GCs and the risk of new onset of T2DM. Copyright © 2018 Elsevier B.V. All rights reserved.

Clinical review: Do glucocorticosteroids alter vitamin D status? A systematic review with meta-analyses of observational studies.

PubMed

Davidson, Zoe E; Walker, Karen Z; Truby, Helen

2012-03-01

Vitamin D supplementation is an important adjunct therapy for the prevention and management of glucocorticoid-induced osteoporosis. There has been little exploration of the relationship between glucocorticosteroid (GCS) use and serum 25-hydroxyvitamin D [25(OH)D]. The aim of this study was to systematically explore how serum 25(OH)D is altered in adult patients receiving GCS. We reviewed Medline and Cinahl databases between January 1970 and August 2011. Experimental studies were included where 25(OH)D was measured in patients more than 18 yr of age receiving GCS therapy. Studies were excluded if patients received at least 400 IU/d (10 μg/d) vitamin D, if GCS treatment was less than 2-wk duration, if more than 50% of the study population received GCS for renal or hepatic disease or after transplant, or if the study population included patients with Cushing's syndrome. A consensus method was used to classify studies. Of identified studies, 3% met the selection criteria. Data were extracted by a single author. Study quality was assessed using criteria developed by the American Dietetic Association. The weighted mean 25(OH)D (by sample size or sd) was 22.4 [95% confidence interval (CI), 19.4, 25.3] ng/ml and 21.0 (95% CI, 13.5, 28.5) ng/ml, respectively. Random effects meta-analysis was used to compare serum 25(OH)D in patients treated with GCS compared to steroid-naive controls (either healthy or with active disease) and in patients before and after GCS administration. Serum 25(OH)D in GCS users was on average -0.5 (95% CI, -1.0, -0.1) ng/ml lower than in healthy controls (P=0.03; I2=56.4%). Serum 25(OH)D did not differ between GCS users and disease controls [standardized mean difference=0.0 (95% CI, -0.2, 0.3) ng/ml; P=0.793; I2=16.2%]. The suboptimal concentrations of serum 25(OH)D found in adults receiving GCS are inadequate for prevention and management of glucocorticoid-induced osteoporosis. Recommendations for vitamin D supplementation should be adjusted accordingly.

Software reliability studies

NASA Technical Reports Server (NTRS)

Wilson, Larry W.

1989-01-01

The longterm goal of this research is to identify or create a model for use in analyzing the reliability of flight control software. The immediate tasks addressed are the creation of data useful to the study of software reliability and production of results pertinent to software reliability through the analysis of existing reliability models and data. The completed data creation portion of this research consists of a Generic Checkout System (GCS) design document created in cooperation with NASA and Research Triangle Institute (RTI) experimenters. This will lead to design and code reviews with the resulting product being one of the versions used in the Terminal Descent Experiment being conducted by the Systems Validations Methods Branch (SVMB) of NASA/Langley. An appended paper details an investigation of the Jelinski-Moranda and Geometric models for software reliability. The models were given data from a process that they have correctly simulated and asked to make predictions about the reliability of that process. It was found that either model will usually fail to make good predictions. These problems were attributed to randomness in the data and replication of data was recommended.

Endothelial Response to Glucocorticoids in Inflammatory Diseases

PubMed Central

Zielińska, Karolina A.; Van Moortel, Laura; Opdenakker, Ghislain; De Bosscher, Karolien; Van den Steen, Philippe E.

2016-01-01

The endothelium plays a crucial role in inflammation. A balanced control of inflammation requires the action of glucocorticoids (GCs), steroidal hormones with potent cell-specific anti-inflammatory properties. Besides the classic anti-inflammatory effects of GCs on leukocytes, recent studies confirm that endothelial cells also represent an important target for GCs. GCs regulate different aspects of endothelial physiology including expression of adhesion molecules, production of pro-inflammatory cytokines and chemokines, and maintenance of endothelial barrier integrity. However, the regulation of endothelial GC sensitivity remains incompletely understood. In this review, we specifically examine the endothelial response to GCs in various inflammatory diseases ranging from multiple sclerosis, stroke, sepsis, and vasculitis to atherosclerosis. Shedding more light on the cross talk between GCs and endothelium will help to improve existing therapeutic strategies and develop new therapies better tailored to the needs of patients. PMID:28018358

Development of new ionic gelation strategy: Towards the preparation of new monodisperse and stable hyaluronic acid/β-cyclodextrin-grafted chitosan nanoparticles as drug delivery carriers for doxorubicin

NASA Astrophysics Data System (ADS)

Mihoub, Amina Ben; Saidat, Boubakeur; Bal, Youssef; Frochot, Céline; Vanderesse, Régis; Acherar, Samir

2018-03-01

In the present study, β-cyclodextrin-grafted chitosan nanoparticles (β-CD- g-CS NPs) were prepared using a new ionic gelation strategy involving a synergistic effect of NaCl (150 mmol/L), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES, 10 mmol/L), and water bath sonication. This new strategy afforded smaller and more monodisperse β-CD- g-CS NPs vs. the classical ionic gelation method. New HA/β-CD- g-CS NPs were also prepared using the above-mentioned strategy by adding hyaluronic acid (HA) to the β-CD- g-CS copolymer at different weight ratios until the ZP values conversion. The best result was obtained with the weight ratio of w(HA): w(β-CD- g-CS) = 2:1 and furnished new spherical and smooth HA/β-CD- g-CS NPs. Furthermore, the stability of β- CD- g-CS NPs and HA/β-CD- g-CS NPs at 4°C in physiological medium (pH 7.4) was compared for 3 weeks period and showed that HA/β-CD- g-CS NPs were more stable all maintaining their monodispersity and high negative ZP values compared to β-CD- g-CS NPs. Finally, preliminary study of HA/β-CD- g-CS NPs as carrier for the controlled release of the anticancer drug doxorubicin was investigated. These new HA/β-CD- g-CS NPs can potentially be used as drug delivery and targeting systems for cancer treatment.

Oxygen-Dependent Globin Coupled Sensor Signaling Modulates Motility and Virulence of the Plant Pathogen Pectobacterium carotovorum.

PubMed

Burns, Justin L; Jariwala, Parth B; Rivera, Shannon; Fontaine, Benjamin M; Briggs, Laura; Weinert, Emily E

2017-08-18

Bacterial pathogens utilize numerous signals to identify the presence of their host and coordinate changes in gene expression that allow for infection. Within plant pathogens, these signals typically include small molecules and/or proteins from their plant hosts and bacterial quorum sensing molecules to ensure sufficient bacterial cell density for successful infection. In addition, bacteria use environmental signals to identify conditions when the host defenses are weakened and potentially to signal entry into an appropriate host/niche for infection. A globin coupled sensor protein (GCS), termed PccGCS, within the soft rot bacterium Pectobacterium carotovorum ssp. carotovorum WPP14 has been identified as an O 2 sensor and demonstrated to alter virulence factor excretion and control motility, with deletion of PccGCS resulting in decreased rotting of a potato host. Using small molecules that modulate bacterial growth and quorum sensing, PccGCS signaling also has been shown to modulate quorum sensing pathways, resulting in the PccGCS deletion strain being more sensitive to plant-derived phenolic acids, which can function as quorum sensing inhibitors, and exhibiting increased N-acylhomoserine lactone (AHL) production. These findings highlight a role for GCS proteins in controlling key O 2 -dependent phenotypes of pathogenic bacteria and suggest that modulating GCS signaling to limit P. carotovorum motility may provide a means to decrease rotting of plant hosts.

Apatite glass-ceramics: a review

NASA Astrophysics Data System (ADS)

Duminis, Tomas; Shahid, Saroash; Hill, Robert Graham

2016-12-01

This article is a review of the published literature on apatite glass-ceramics (GCs). Topics covered include crystallization mechanisms of the various families of the apatite GCs and an update on research and development on apatite GCs for applications in orthopedics, dentistry, optoelectronics and nuclear waste management. Most apatite GCs crystallize through a homogenous nucleation and crystallization mechanism, which is aided by a prior liquid-liquid phase separation. Careful control of the base glass composition and heat-treatment conditions, which determine the nature and morphology of the crystal phases in the GC can produce GC materials with exceptional thermal, mechanical, optical and biological properties. The GCs reviewed for orthopedic applications exhibit suitable mechanical properties and can chemically bond to bone and stimulate its regeneration. The most commercially successful apatite GCs are those developed for dental veneering. These materials exhibit excellent translucency and clinical esthetics, and mimic the natural tooth mineral. Due to the ease of solid solution of the apatite lattice, rare earth doped apatite GCs are discussed for potential applications in optoelectronics and nuclear waste management. One of the drawbacks of the commercial apatite GCs used in orthopedics is the lack of resorbability, therefore the review provides a direction for future research in the field.

Pilot Aircraft Interface Objectives/Rationale

NASA Technical Reports Server (NTRS)

Shively, Jay

2010-01-01

Objective: Database and proof of concept for guidelines for GCS compliance a) Rationale: 1) Provide research test-bed to develop guidelines. 2) Modify GCS for NAS Compliance to provide proof of concept. b) Approach: 1) Assess current state of GCS technology. 2) Information Requirements Definition. 3) SME Workshop. 4) Modify an Existing GCS for NAS Compliance. 5) Define exemplar UAS (choose system to develop prototype). 6) Define Candidate Displays & Controls. 7) Evaluate/ refine in Simulations. 8) Demonstrate in flight. c) Deliverables: 1) Information Requirements Report. 2) Workshop Proceedings. 3) Technical Reports/ papers on Simulations & Flight Demo. 4) Database for guidelines.

Using the abbreviated injury severity and Glasgow Coma Scale scores to predict 2-week mortality after traumatic brain injury.

PubMed

Timmons, Shelly D; Bee, Tiffany; Webb, Sharon; Diaz-Arrastia, Ramon R; Hesdorffer, Dale

2011-11-01

Prediction of outcome after traumatic brain injury (TBI) remains elusive. We tested the use of a single hospital Glasgow Coma Scale (GCS) Score, GCS Motor Score, and the Head component of the Abbreviated Injury Scale (AIS) Score to predict 2-week cumulative mortality in a large cohort of TBI patients admitted to the eight U.S. Level I trauma centers in the TBI Clinical Trials Network. Data on 2,808 TBI patients were entered into a centralized database. These TBI patients were categorized as severe (GCS score, 3-8), moderate (9-12), or complicated mild (13-15 with positive computed tomography findings). Intubation and chemical paralysis were recorded. The cumulative incidence of mortality in the first 2 weeks after head injury was calculated using Kaplan-Meier survival analysis. Cox proportional hazards regression was used to estimate the magnitude of the risk for 2-week mortality. Two-week cumulative mortality was independently predicted by GCS, GCS Motor Score, and Head AIS. GCS Severity Category and GCS Motor Score were stronger predictors of 2-week mortality than Head AIS. There was also an independent effect of age (<60 vs. ≥60) on mortality after controlling for both GCS and Head AIS Scores. Anatomic and physiologic scales are useful in the prediction of mortality after TBI. We did not demonstrate any added benefit to combining the total GCS or GCS Motor Scores with the Head AIS Score in the short-term prediction of death after TBI.

Comparative assessment of a DNA and protein Leishmania donovani gamma glutamyl cysteine synthetase vaccine to cross-protect against murine cutaneous leishmaniasis caused by L. major or L. mexicana infection.

PubMed

Campbell, S A; Alawa, J; Doro, B; Henriquez, F L; Roberts, C W; Nok, A; Alawa, C B I; Alsaadi, M; Mullen, A B; Carter, K C

2012-02-08

Leishmaniasis is a major health problem and it is estimated that 12 million people are currently infected. A vaccine which could cross-protect people against different Leishmania spp. would facilitate control of this disease as more than one species of Leishmania may be present. In this study the ability of a DNA vaccine, using the full gene sequence for L. donovani gamma glutamyl cysteine synthetase (γGCS) incorporated in the pVAX vector (pVAXγGCS), and a protein vaccine, using the corresponding recombinant L. donovani γGCS protein (LdγGCS), to protect against L. major or L. mexicana infection was evaluated. DNA vaccination gave transient protection against L. major and no protection against L. mexicana despite significantly enhancing specific antibody titres in vaccinated infected mice compared to infected controls. Vaccination with the LdγGCS protected against both species but only if the protein was incorporated into non-ionic surfactant vesicles for L. mexicana. The results of this study indicate that a L. donovani γGCS vaccine could be used to vaccinate against more than one Leishmania species but only if the recombinant protein is used. Copyright © 2012 Elsevier Ltd. All rights reserved.

Somatic cells initiate primordial follicle activation and govern the development of dormant oocytes in mice.

PubMed

Zhang, Hua; Risal, Sanjiv; Gorre, Nagaraju; Busayavalasa, Kiran; Li, Xin; Shen, Yan; Bosbach, Benedikt; Brännström, Mats; Liu, Kui

2014-11-03

The majority of oocytes in the mammalian ovary are dormant oocytes that are enclosed in primordial follicles by several somatic cells, which we refer to as primordial follicle granulosa cells (pfGCs). Very little is known, however, about how the pfGCs control the activation of primordial follicles and the developmental fates of dormant oocytes. By targeting molecules in pfGCs with several mutant mouse models, we demonstrate that the somatic pfGCs initiate the activation of primordial follicles and govern the quiescence or awakening of dormant oocytes. Inhibition of mTORC1 signaling in pfGCs prevents the differentiation of pfGCs into granulosa cells, and this arrests the dormant oocytes in their quiescent states, leading to oocyte death. Overactivation of mTORC1 signaling in pfGCs accelerates the differentiation of pfGCs into granulosa cells and causes premature activation of all dormant oocytes and primordial follicles. We further show that pfGCs trigger the awakening of dormant oocytes through KIT ligand (KITL), and we present an essential communication network between the somatic cells and germ cells that is based on signaling between the mTORC1-KITL cascade in pfGCs and KIT-PI3K signaling in oocytes. Our findings provide a relatively complete picture of how mammalian primordial follicles are activated. The microenvironment surrounding primordial follicles can activate mTORC1-KITL signaling in pfGCs, and these cells trigger the awakening of dormant oocytes and complete the process of follicular activation. Such communication between the microenvironment, somatic cells, and germ cells is essential to maintaining the proper reproductive lifespan in mammals. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of replacing lactose by starch on protein and fat digestion in milk-fed veal calves.

PubMed

Pluschke, A M; Gilbert, M S; Williams, B A; van den Borne, J J G C; Schols, H A; Gerrits, W J J

2016-08-01

Replacing dairy components from milk replacer (MR) with vegetable products has been previously associated with decreased protein and fat digestibility in milk-fed calves resulting in lower live weight gain. In this experiment, the major carbohydrate source in MR, lactose, was partly replaced with gelatinized corn starch (GCS) to determine the effect on protein and fat digestibility in milk-fed calves. In total, 16 male Holstein-Friesian calves received either MR with lactose as the carbohydrate source (control) or 18% GCS at the expense of lactose. In the adaptation period, calves were exposed to an increasing dose of GCS for 14 weeks. The indigestible marker cobalt ethylenediaminetetraacetic acid was incorporated into the MR for calculating apparent nutrient digestibility, whereas a pulse dose of chromium (Cr) chloride was fed with the last MR meal 4 h before slaughter as an indicator of passage rates. The calves were anesthetized and exsanguinated at 30 weeks of age. The small intestine was divided in three; small intestine 1 and 2 (SI1 and SI2, respectively) and the terminal ileum (last ~100 cm of small intestine) and samples of digesta were collected. Small intestinal digesta was analysed for α-amylase, lipase and trypsin activity. Digestibility of protein was determined for SI1, SI2, ileum and total tract, whereas digestibility of fat was determined for SI1, SI2 and total tract. Apparent protein digestibility in the small intestine did not differ between treatments but was higher in control calves at total tract level. Apparent crude fat digestibility tended to be increased in SI1 and SI2 for GCS calves, but no difference was found at total tract level. Activity of α-amylase in SI2 and lipase in both SI1 and SI2 was higher in GCS calves. Activity of trypsin tended to be higher in control calves and was higher in SI1 compared with SI2. A lower recovery of Cr in SI2 and a higher recovery of Cr in the large intestine suggest an increased rate of passage for GCS calves. Including 18% of GCS in a milk replacer at the expense of lactose increased passage rate and decreased apparent total tract protein digestibility. In the small intestine, protein digestion did not decrease when feeding GCS and fat digestion even tended to increase. Overall, effects on digestion might be levelled when partially replacing lactose with GCS, because starch digestion is lower than that of lactose but fat digestion may be slightly increased when feeding GCS.

A dual role for glucocorticoid-induced leucine zipper in glucocorticoid function: tumor growth promotion or suppression?

PubMed

Ayroldi, Emira; Cannarile, Lorenza; Delfino, Domenico V; Riccardi, Carlo

2018-04-26

Glucocorticoids (GCs), important therapeutic tools to treat inflammatory and immunosuppressive diseases, can also be used as part of cancer therapy. In oncology, GCs are used as anticancer drugs for lymphohematopoietic malignancies, while in solid neoplasms primarily to control the side effects of chemo/radiotherapy treatments. The molecular mechanisms underlying the effects of GCs are numerous and often overlapping, but not all have been elucidated. In normal, cancerous, and inflammatory tissues, the response to GCs differs based on the tissue type. The effects of GCs are dependent on several factors: the tumor type, the GC therapy being used, the expression level of the glucocorticoid receptor (GR), and the presence of any other stimuli such as signals from immune cells and the tumor microenvironment. Therefore, GCs may either promote or suppress tumor growth via different molecular mechanisms. Stress exposure results in dysregulation of the hypothalamic-pituitary-adrenal axis with increased levels of endogenous GCs that promote tumorigenesis, confirming the importance of GCs in tumor growth. Most of the effects of GCs are genomic and mediated by the modulation of GR gene transcription. Moreover, among the GR-induced genes, glucocorticoid-induced leucine zipper (GILZ), which was cloned and characterized primarily in our laboratory, mediates many GC anti-inflammatory effects. In this review, we analyzed the possible role for GILZ in the effects GCs have on tumors cells. We also suggest that GILZ, by affecting the immune system, tumor microenvironment, and directly cancer cell biology, has a tumor-promoting function. However, it may also induce apoptosis or decrease the proliferation of cancer cells, thus inhibiting tumor growth. The potential therapeutic implications of GILZ activity on tumor cells are discussed here.

Physiological effects of wearing graduated compression stockings during running.

PubMed

Ali, Ajmol; Creasy, Robert H; Edge, Johann A

2010-08-01

This study examined the effect of wearing different grades of graduated compression stockings (GCS) on physiological and perceptual measures during and following treadmill running in competitive runners. Nine males and one female performed three 40-min treadmill runs (80 +/- 5% maximal oxygen uptake) wearing either control (0 mmHg; CON), low (12-15 mmHg; LO-GCS), or high (23-32 mmHg; HI-GCS) grade GCS in a double-blind counterbalanced order. Oxygen uptake, heart rate and blood lactate were measured. Perceptual scales were used pre- and post-run to assess comfort, tightness and any pain associated with wearing GCS. Changes in muscle function, soreness and damage were determined pre-run, immediately after running and 24 and 48 h post-run by measuring creatine kinase and myoglobin, counter-movement jump height, perceived soreness diagrams, and pressure sensitivity. There were no significant differences between trials for oxygen uptake, heart rate or blood lactate during exercise. HI-GCS was perceived as tighter (P < 0.05) and more pain-inducing (P < 0.05) than the other interventions; CON and LO-GCS were rated more comfortable than HI-GCS (P < 0.05). Creatine kinase (P < 0.05), myoglobin (P < 0.05) and jump height (P < 0.05) were higher and pressure sensitivity was more pronounced (P < 0.05) immediately after running but not after 24 and 48 h. Only four participants reported muscle soreness during recovery from running and there were no differences in muscle function between trials. In conclusion, healthy runners wearing GCS did not experience any physiological benefits during or following treadmill running. However, athletes felt more comfortable wearing low-grade GCS whilst running.

T regulatory cells participate in the control of germinal centre reactions

PubMed Central

Alexander, Carla-Maria; Tygrett, Lorraine T; Boyden, Alexander W; Wolniak, Kristy L; Legge, Kevin L; Waldschmidt, Thomas J

2011-01-01

Germinal centre (GC) reactions are central features of T-cell-driven B-cell responses, and the site where antibody-producing cells and memory B cells are generated. Within GCs, a range of complex cellular and molecular events occur which are critical for the generation of high affinity antibodies. These processes require exquisite regulation not only to ensure the production of desired antibodies, but to minimize unwanted autoreactive or low affinity antibodies. To assess whether T regulatory (Treg) cells participate in the control of GC responses, immunized mice were treated with an anti-glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR) monoclonal antibody (mAb) to disrupt Treg-cell activity. In anti-GITR-treated mice, the GC B-cell pool was significantly larger compared with control-treated animals, with switched GC B cells composing an abnormally high proportion of the response. Dysregulated GCs were also observed regardless of strain, T helper type 1 or 2 polarizing antigens, and were also seen after anti-CD25 mAb treatment. Within the spleens of immunized mice, CXCR5+ and CCR7− Treg cells were documented by flow cytometry and Foxp3+ cells were found within GCs using immunohistology. Final studies demonstrated administration of either anti-transforming growth factor-β or anti-interleukin-10 receptor blocking mAb to likewise result in dysregulated GCs, suggesting that generation of inducible Treg cells is important in controlling the GC response. Taken together, these findings indicate that Treg cells contribute to the overall size and quality of the humoral response by controlling homeostasis within GCs. PMID:21635248

An Ecological Approach to the Design of UAV Ground Control Station (GCS) Status Displays

NASA Technical Reports Server (NTRS)

Dowell, Susan; Morphew, Ephimia; Shively, Jay

2003-01-01

Use of UAVs in military and commercial applications will continue to increase. However, there has been limited research devoted to UAV GCS design. The current study employed an ecological approach to interfac e design. Ecological Interface Design (EID) can be characterized as r epresenting the properties of a system, such that an operator is enco uraged to use skill-based behavior when problem solving. When more ef fortful cognitive processes become necessary due to unfamiliar situations, the application of EID philosophy supports the application of kn owledge-based behavior. With advances toward multiple UAV command and control, operators need GCS interfaces designed to support understan ding of complex systems. We hypothesized that use of EID principles f or the display of UAV status information would result in better opera tor performance and situational awareness, while decreasing workload. Pilots flew a series of missions with three UAV GCS displays of statu s information (Alphanumeric, Ecological, and Hybrid display format). Measures of task performance, Situational Awareness, and workload dem onstrated the benefits of using an ecological approach to designing U AV GCS displays. The application of ecological principles to the design of UAV GCSs is a promising area for improving UAV operations.

NR2B-dependent plasticity of adult-born granule cells is necessary for context discrimination.

PubMed

Kheirbek, Mazen A; Tannenholz, Lindsay; Hen, René

2012-06-20

Adult-generated granule cells (GCs) in the dentate gyrus (DG) exhibit a period of heightened plasticity 4-6 weeks postmitosis. However, the functional contribution of this critical window of plasticity to hippocampal neurogenesis and behavior remains unknown. Here, we show that deletion of NR2B-containing NMDA receptors from adult-born GCs impairs a neurogenesis-dependent form of LTP in the DG and reduces dendritic complexity of adult-born GCs, but does not impact their survival. Mice in which the NR2B-containing NMDA receptor was deleted from adult-born GCs did not differ from controls in baseline anxiety-like behavior or discrimination of very different contexts, but were impaired in discrimination of highly similar contexts. These results indicate that NR2B-dependent plasticity of adult-born GCs is necessary for fine contextual discrimination and is consistent with their proposed role in pattern separation.

Disclosing genetic risk for coronary heart disease: effects on perceived personal control and genetic counseling satisfaction.

PubMed

Robinson, C L; Jouni, H; Kruisselbrink, T M; Austin, E E; Christensen, K D; Green, R C; Kullo, I J

2016-02-01

We investigated whether disclosure of coronary heart disease (CHD) genetic risk influences perceived personal control (PPC) and genetic counseling satisfaction (GCS). Participants (n = 207, age: 45-65 years) were randomized to receive estimated 10-year risk of CHD based on a conventional risk score (CRS) with or without a genetic risk score (GRS). Risk estimates were disclosed by a genetic counselor who also reviewed how GRS altered risk in those randomized to CRS+GRS. Each participant subsequently met with a physician and then completed surveys to assess PPC and GCS. Participants who received CRS+GRS had higher PPC than those who received CRS alone although the absolute difference was small (25.2 ± 2.7 vs 24.1 ± 3.8, p = 0.04). A greater proportion of CRS+GRS participants had higher GCS scores (17.3 ± 5.3 vs 15.9 ± 6.3, p = 0.06). In the CRS+GRS group, PPC and GCS scores were not correlated with GRS. Within both groups, PPC and GCS scores were similar in patients with or without family history (p = NS). In conclusion, patients who received their genetic risk of CHD had higher PPC and tended to have higher GCS. Our findings suggest that disclosure of genetic risk of CHD together with conventional risk estimates is appreciated by patients. Whether this results in improved outcomes needs additional investigation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Adaptive capacity of geographical clusters: Complexity science and network theory approach

NASA Astrophysics Data System (ADS)

Albino, Vito; Carbonara, Nunzia; Giannoccaro, Ilaria

This paper deals with the adaptive capacity of geographical clusters (GCs), that is a relevant topic in the literature. To address this topic, GC is considered as a complex adaptive system (CAS). Three theoretical propositions concerning the GC adaptive capacity are formulated by using complexity theory. First, we identify three main properties of CAS s that affect the adaptive capacity, namely the interconnectivity, the heterogeneity, and the level of control, and define how the value of these properties influence the adaptive capacity. Then, we associate these properties with specific GC characteristics so obtaining the key conditions of GCs that give them the adaptive capacity so assuring their competitive advantage. To test these theoretical propositions, a case study on two real GCs is carried out. The considered GCs are modeled as networks where firms are nodes and inter-firms relationships are links. Heterogeneity, interconnectivity, and level of control are considered as network properties and thus measured by using the methods of the network theory.

Autophagy in Drosophila ovaries is induced by starvation and is required for oogenesis.

PubMed

Barth, J M I; Szabad, J; Hafen, E; Köhler, K

2011-06-01

Autophagy, an evolutionarily conserved lysosome-mediated degradation, promotes cell survival under starvation and is controlled by insulin/target of rapamycin (TOR) signaling. In Drosophila, nutrient depletion induces autophagy in the fat body. Interestingly, nutrient availability and insulin/TOR signaling also influence the size and structure of Drosophila ovaries, however, the role of nutrient signaling and autophagy during this process remains to be elucidated. Here, we show that starvation induces autophagy in germline cells (GCs) and in follicle cells (FCs) in Drosophila ovaries. This process is mediated by the ATG machinery and involves the upregulation of Atg genes. We further demonstrate that insulin/TOR signaling controls autophagy in FCs and GCs. The analysis of chimeric females reveals that autophagy in FCs, but not in GCs, is required for egg development. Strikingly, when animals lack Atg gene function in both cell types, ovaries develop normally, suggesting that the incompatibility between autophagy-competent GCs and autophagy-deficient FCs leads to defective egg development. As egg morphogenesis depends on a tightly linked signaling between FCs and GCs, we propose a model in which autophagy is required for the communication between these two cell types. Our data establish an important function for autophagy during oogenesis and contributes to the understanding of the role of autophagy in animal development.

Effect of Age on Glasgow Coma Scale in Patients with Moderate and Severe Traumatic Brain Injury: An Approach with Propensity Score-Matched Population.

PubMed

Rau, Cheng-Shyuan; Wu, Shao-Chun; Chen, Yi-Chun; Chien, Peng-Chen; Hsieh, Hsiao-Yun; Kuo, Pao-Jen; Hsieh, Ching-Hua

2017-11-13

Background: The most widely used methods of describing traumatic brain injury (TBI) are the Glasgow Coma Scale (GCS) and the Abbreviated Injury Scale (AIS). Recent evidence suggests that presenting GCS in older patients may be higher than that in younger patients for an equivalent anatomical severity of TBI. This study aimed to assess these observations with a propensity-score matching approach using the data from Trauma Registry System in a Level I trauma center. Methods: We included all adult patients (aged ≥20 years old) with moderate to severe TBI from 1 January 2009 to 31 December 2016. Patients were categorized into elderly (aged ≥65 years) and young adults (aged 20-64 years). The severity of TBI was defined by an AIS score in the head (AIS 3‒4 and 5 indicate moderate and severe TBI, respectively). We examined the differences in the GCS scores by age at each head AIS score. Unpaired Student's t - and Mann-Whitney U -tests were used to analyze normally and non-normally distributed continuous data, respectively. Categorical data were compared using either the Pearson chi-square or two-sided Fisher's exact tests. Matched patient populations were allocated in a 1:1 ratio according to the propensity scores calculated using NCSS software with the following covariates: sex, pre-existing chronic obstructive pulmonary disease, systolic blood pressure, hemoglobin, sodium, glucose, and alcohol level. Logistic regression was used to evaluate the effects of age on the GCS score in each head AIS stratum. Results: The study population included 2081 adult patients with moderate to severe TBI. These patients were categorized into elderly ( n = 847) and young adults ( n = 1234): each was exclusively further divided into three groups of patients with head AIS of 3, 4, or 5. In the 162 well-balanced pairs of TBI patients with head AIS of 3, the elderly demonstrated a significantly higher GCS score than the young adults (14.1 ± 2.2 vs. 13.1 ± 3.3, respectively; p = 0.002). In the 362 well-balanced pairs of TBI patients with head AIS of 4, the elderly showed a significantly higher GCS score than the young adults (13.1 ± 3.3 vs. 12.2 ± 3.8, respectively; p = 0.002). In the 89 well-balance pairs of TBI patients with head AIS of 5, no significant differences were observed for the GCS scores. Conclusions: This study demonstrated that elderly patients with moderate TBI present higher GCS score than younger patients. This study underscores the importance of determining of TBI severity in this group of elderly patients based on the GCS score alone. A lower threshold of GCS cutoff should be adopted in the management of the elderly patients with TBI.

A Subtype of Olfactory Bulb Interneurons Is Required for Odor Detection and Discrimination Behaviors.

PubMed

Takahashi, Hiroo; Ogawa, Yoichi; Yoshihara, Sei-Ichi; Asahina, Ryo; Kinoshita, Masahito; Kitano, Tatsuro; Kitsuki, Michiko; Tatsumi, Kana; Okuda, Mamiko; Tatsumi, Kouko; Wanaka, Akio; Hirai, Hirokazu; Stern, Peter L; Tsuboi, Akio

2016-08-03

Neural circuits that undergo reorganization by newborn interneurons in the olfactory bulb (OB) are necessary for odor detection and discrimination, olfactory memory, and innate olfactory responses, including predator avoidance and sexual behaviors. The OB possesses many interneurons, including various types of granule cells (GCs); however, the contribution that each type of interneuron makes to olfactory behavioral control remains unknown. Here, we investigated the in vivo functional role of oncofetal trophoblast glycoprotein 5T4, a regulator for dendritic arborization of 5T4-expressing GCs (5T4 GCs), the level of which is reduced in the OB of 5T4 knock-out (KO) mice. Electrophysiological recordings with acute OB slices indicated that external tufted cells (ETCs) can be divided into two types, bursting and nonbursting. Optogenetic stimulation of 5T4 GCs revealed their connection to both bursting and nonbursting ETCs, as well as to mitral cells (MCs). Interestingly, nonbursting ETCs received fewer inhibitory inputs from GCs in 5T4 KO mice than from those in wild-type (WT) mice, whereas bursting ETCs and MCs received similar inputs in both mice. Furthermore, 5T4 GCs received significantly fewer excitatory inputs in 5T4 KO mice. Remarkably, in olfactory behavior tests, 5T4 KO mice had higher odor detection thresholds than the WT, as well as defects in odor discrimination learning. Therefore, the loss of 5T4 attenuates inhibitory inputs from 5T4 GCs to nonbursting ETCs and excitatory inputs to 5T4 GCs, contributing to disturbances in olfactory behavior. Our novel findings suggest that, among the various types of OB interneurons, the 5T4 GC subtype is required for odor detection and discrimination behaviors. Neuronal circuits in the brain include glutamatergic principal neurons and GABAergic interneurons. Although the latter is a minority cell type, they are vital for normal brain function because they regulate the activity of principal neurons. If interneuron function is impaired, brain function may be damaged, leading to behavior disorder. The olfactory bulb (OB) possesses various types of interneurons, including granule cells (GCs); however, the contribution that each type of interneuron makes to the control of olfactory behavior remains unknown. Here, we analyzed electrophysiologically and behaviorally the function of oncofetal trophoblast glycoprotein 5T4, a regulator for dendritic branching in OB GCs. We found that, among the various types of OB interneuron, the 5T4 GC subtype is required for odor detection and odor discrimination behaviors. Copyright © 2016 the authors 0270-6474/16/368211-18$15.00/0.

Effect of Memantine on Serum Levels of Neuron-Specific Enolase and on the Glasgow Coma Scale in Patients With Moderate Traumatic Brain Injury.

PubMed

Mokhtari, Majid; Nayeb-Aghaei, Hossein; Kouchek, Mehran; Miri, Mir Mohammad; Goharani, Reza; Amoozandeh, Arash; Akhavan Salamat, Sina; Sistanizad, Mohammad

2018-01-01

Traumatic brain injury (TBI) is a major cause of disability and death globally. Despite significant progress in neuromonitoring and neuroprotection, pharmacological interventions have failed to generate favorable results. We examined the effect of memantine on serum levels of neuron-specific enolase (NSE), a marker of neuronal damage, and the Glasgow Coma Scale (GCS) in patients with moderate TBI. Patients were randomly assigned to the control group (who received standard TBI management) and the treatment group (who, alongside their standard management, received enteral memantine 30 mg twice daily for 7 days). Patients' clinical data, GCS, findings of head computed tomography, and serum NSE levels were collected during the study. Forty-one patients were randomized into the control and treatment groups, 19 and 22 patients respectively. Baseline characteristics and serum NSE levels were not significantly different between the 2 groups. The mean serum NSE levels for the memantine and the control groups on day 3 were 7.95 ± 2.86 and 12.33 ± 7.09 ng/mL, respectively (P = .05), and on day 7 were 5.03 ± 3.25 and 10.04 ± 5.72 ng/mL, respectively (P = .003). The mean GCS on day 3 was 12.3 ± 2.0 and 10.9 ± 1.9 in the memantine and control groups, respectively (P = .03). Serum NSE levels and GCS changes were negatively correlated (r = -0.368, P = .02). Patients with moderate TBI who received memantine had significantly reduced serum NSE levels by day 7 and marked improvement in their GCS scores on day 3 of the study. © 2017, The American College of Clinical Pharmacology.

Mucoadhesive properties of low molecular weight chitosan- or glycol chitosan- and corresponding thiomer-coated poly(isobutylcyanoacrylate) core-shell nanoparticles.

PubMed

Palazzo, Claudio; Trapani, Giuseppe; Ponchel, Gilles; Trapani, Adriana; Vauthier, Christine

2017-08-01

The aim of the present work was to evaluate the mucoadhesive properties of poly(isobutyl cyanoacrylate) (PIBCA) nanoparticles (NPs) coated with Low Molecular Weight (LMW) chitosan (CS)- and glycol chitosan (GCS)-based thiomers as well as with the corresponding LMW unmodified polysaccharides. For this purpose, all the CS- and GCS-based thiomers were prepared under simple and mild conditions starting from the LMW unmodified polymers CS and GCS. The resulting NPs were of spherical shape with diameters ranging from 400 to 600nm and 187 to 309nm, for CS- and GCS-based NPs, respectively. The mucoadhesive characteristics of these core shell NPs were studied in Ussing chambers measuring the percentage of NPs stuck on the mucosal of fresh intestinal tissue after 2h of incubation. Moreover, incubation of nanoparticle formulations with the intestinal tissue induced changes in transmucosal electrical resistance which were measured to gain information into the opening of tight junctions and to control the integrity of the mucosa. Thus, it was found that PIBCA NPs coated with the GCS-Glutathione conjugate (GCGPIBCA NPs) possessed the most favorable mucoadhesive performances. Moreover, both GCGPIBCA- and GCS-N-acetyl-cysteine (GCNPIBCA)-core-shell NPs might induced an enlargement of the epithelial cell tight junctions. In conclusion, coating of PIBCA NPs with GCS-based thiomers may be useful for improving the mucoadhesive and permeation properties of these nanocarriers. Copyright © 2017 Elsevier B.V. All rights reserved.

Weaker control of the electrical properties of cerebellar granule cells by tonically active GABAA receptors in the Ts65Dn mouse model of Down’s syndrome

PubMed Central

2013-01-01

Background Down’s syndrome (DS) is caused by triplication of all or part of human chromosome 21 and is characterized by a decrease in the overall size of the brain. One of the brain regions most affected is the cerebellum, in which the number of granule cells (GCs) is markedly decreased. GCs process sensory information entering the cerebellum via mossy fibres and pass it on to Purkinje cells and inhibitory interneurons. How GCs transform incoming signals depends on their input–output relationship, which is adjusted by tonically active GABAA receptor channels. Results We report that in the Ts65Dn mouse model of DS, in which cerebellar volume and GC number are decreased as in DS, the tonic GABAA receptor current in GCs is smaller than in wild-type mice and is less effective in moderating input resistance and raising the minimum current required for action potential firing. We also find that tonically active GABAA receptors curb the height and broaden the width of action potentials in wild-type GCs but not in Ts65Dn GCs. Single-cell real-time quantitative PCR reveals that these electrical differences are accompanied by decreased expression of the gene encoding the GABAA receptor β3 subunit but not genes coding for some of the other GABAA receptor subunits expressed in GCs (α1, α6, β2 and δ). Conclusions Weaker moderation of excitability and action potential waveform in GCs of the Ts65Dn mouse by tonically active GABAA receptors is likely to contribute to atypical transfer of information through the cerebellum. Similar changes may occur in DS. PMID:23870245

Aberrant expression and DNA methylation of lipid metabolism genes in PCOS: a new insight into its pathogenesis.

PubMed

Pan, Jie-Xue; Tan, Ya-Jing; Wang, Fang-Fang; Hou, Ning-Ning; Xiang, Yu-Qian; Zhang, Jun-Yu; Liu, Ye; Qu, Fan; Meng, Qing; Xu, Jian; Sheng, Jian-Zhong; Huang, He-Feng

2018-01-01

Polycystic ovary syndrome (PCOS), whose etiology remains uncertain, is a highly heterogenous and genetically complex endocrine disorder. The aim of this study was to identify differentially expressed genes (DEGs) in granulosa cells (GCs) from PCOS patients and make epigenetic insights into the pathogenesis of PCOS. Included in this study were 110 women with PCOS and 119 women with normal ovulatory cycles undergoing in vitro fertilization acting as the control group. RNA-seq identified 92 DEGs unique to PCOS GCs in comparison with the control group. Bioinformatic analysis indicated that synthesis of lipids and steroids was activated in PCOS GCs. 5-Methylcytosine analysis demonstrated that there was an approximate 25% reduction in global DNA methylation of GCs in PCOS women (4.44 ± 0.65%) compared with the controls (6.07 ± 0.72%; P  < 0.05). Using MassArray EpiTYPER quantitative DNA methylation analysis, we also found hypomethylation of several gene promoters related to lipid and steroid synthesis, which might result in the aberrant expression of these genes. Our results suggest that hypomethylated genes related to the synthesis of lipid and steroid may dysregulate expression of these genes and promote synthesis of steroid hormones including androgen, which could partially explain mechanisms of hyperandrogenism in PCOS.

Effects of severity of traumatic brain injury and brain reserve on cognitive-control related brain activation.

PubMed

Scheibel, Randall S; Newsome, Mary R; Troyanskaya, Maya; Steinberg, Joel L; Goldstein, Felicia C; Mao, Hui; Levin, Harvey S

2009-09-01

Functional magnetic resonance imaging (fMRI) has revealed more extensive cognitive-control related brain activation following traumatic brain injury (TBI), but little is known about how activation varies with TBI severity. Thirty patients with moderate to severe TBI and 10 with orthopedic injury (OI) underwent fMRI at 3 months post-injury using a stimulus response compatibility task. Regression analyses indicated that lower total Glasgow Coma Scale (GCS) and GCS verbal component scores were associated with higher levels of brain activation. Brain-injured patients were also divided into three groups based upon their total GCS score (3-4, 5-8, or 9-15), and patients with a total GCS score of 8 or less produced increased, diffuse activation that included structures thought to mediate visual attention and cognitive control. The cingulate gyrus and thalamus were among the areas showing greatest increases, and this is consistent with vulnerability of these midline structures in severe, diffuse TBI. Better task performance was associated with higher activation, and there were differences in the over-activation pattern that varied with TBI severity, including greater reliance upon left-lateralized brain structures in patients with the most severe injuries. These findings suggest that over-activation is at least partially effective for improving performance and may be compensatory.

Effect of Massage Therapy on Vital Signs and GCS Scores of ICU Patients: A Randomized Controlled Clinical Trial

PubMed Central

Vahedian-Azimi, Amir; Ebadi, Abbas; Asghari Jafarabadi, Mohammad; Saadat, Soheil; Ahmadi, Fazlollah

2014-01-01

Background: Unalleviated complications related to hospitalization, including stress, anxiety, and pain, can easily influence different structures, like the neural system, by enhancing the stimulation of sympathetic nervous pathways and causing unstable vital signs and deterioration in the level of consciousness. Objectives: The purpose of this study was to determine the effects of massage therapy by family members on vital signs and Glasgow Coma Scale Score (GCS) of patients hospitalized in the Intensive Care Unit (ICU). Patients and Methods: This randomized controlled clinical trial was conducted at the ICU of the Shariati Hospital during 2012; 45 ICU patients and 45 family members in the experimental group and the same number of patients and family members in the control group were consecutively selected . The data collection instrument consisted of two parts. The first part included demographic data (age, marital status and Body Mass Index) and the second part included a checklist to record the patient’s vital signs (systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR), pulse rate (PR)) and GCS. All measurements were done at the same time in both groups before the intervention (full body massage therapy), and 1 hour, 2 hours, 3 hours, and 4 hours after intervention. The patients were provided with a 60-minute full body massage The massage protocol included static, surface tension, stretching, superficial lymph unload, transverse friction, and myofacial releasing techniques. Results: Significant differences were observed between experimental and control groups in the SBP at 1 hour, SBP 2 hours, and SBP 3 hours, and also in GCS at 1 hour to GCS at 4 hours (P < 0.05). Multivariate analysis revealed a significant difference between experimental and control groups in SBP at all time points (P < 0.05). Conclusions: Massage via family members had several positive effects on the patients’ clinical conditions, and therefore, it should be recognized as one of the most important clinical considerations in hospitalized patients. PMID:25337518

Effect of Massage Therapy on Vital Signs and GCS Scores of ICU Patients: A Randomized Controlled Clinical Trial.

PubMed

Vahedian-Azimi, Amir; Ebadi, Abbas; Asghari Jafarabadi, Mohammad; Saadat, Soheil; Ahmadi, Fazlollah

2014-08-01

Unalleviated complications related to hospitalization, including stress, anxiety, and pain, can easily influence different structures, like the neural system, by enhancing the stimulation of sympathetic nervous pathways and causing unstable vital signs and deterioration in the level of consciousness. The purpose of this study was to determine the effects of massage therapy by family members on vital signs and Glasgow Coma Scale Score (GCS) of patients hospitalized in the Intensive Care Unit (ICU). This randomized controlled clinical trial was conducted at the ICU of the Shariati Hospital during 2012; 45 ICU patients and 45 family members in the experimental group and the same number of patients and family members in the control group were consecutively selected . The data collection instrument consisted of two parts. The first part included demographic data (age, marital status and Body Mass Index) and the second part included a checklist to record the patient's vital signs (systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR), pulse rate (PR)) and GCS. All measurements were done at the same time in both groups before the intervention (full body massage therapy), and 1 hour, 2 hours, 3 hours, and 4 hours after intervention. The patients were provided with a 60-minute full body massage The massage protocol included static, surface tension, stretching, superficial lymph unload, transverse friction, and myofacial releasing techniques. Significant differences were observed between experimental and control groups in the SBP at 1 hour, SBP 2 hours, and SBP 3 hours, and also in GCS at 1 hour to GCS at 4 hours (P < 0.05). Multivariate analysis revealed a significant difference between experimental and control groups in SBP at all time points (P < 0.05). Massage via family members had several positive effects on the patients' clinical conditions, and therefore, it should be recognized as one of the most important clinical considerations in hospitalized patients.

Similarities between GCS and human motor cortex: complex movement coordination

NASA Astrophysics Data System (ADS)

Rodríguez, Jose A.; Macias, Rosa; Molgo, Jordi; Guerra, Dailos

2014-07-01

The "Gran Telescopio de Canarias" (GTC1) is an optical-infrared 10-meter segmented mirror telescope at the ORM observatory in Canary Islands (Spain). The GTC control system (GCS), the brain of the telescope, is is a distributed object & component oriented system based on RT-CORBA and it is responsible for the management and operation of the telescope, including its instrumentation. On the other hand, the Human motor cortex (HMC) is a region of the cerebrum responsible for the coordination of planning, control, and executing voluntary movements. If we analyze both systems, as far as the movement control of their mechanisms and body parts is concerned, we can find extraordinary similarities in their architectures. Both are structured in layers, and their functionalities are comparable from the movement conception until the movement action itself: In the GCS we can enumerate the Sequencer high level components, the Coordination libraries, the Control Kit library and the Device Driver library as the subsystems involved in the telescope movement control. If we look at the motor cortex, we can also enumerate the primary motor cortex, the secondary motor cortices, which include the posterior parietal cortex, the premotor cortex, and the supplementary motor area (SMA), the motor units, the sensory organs and the basal ganglia. From all these components/areas we will analyze in depth the several subcortical regions, of the the motor cortex, that are involved in organizing motor programs for complex movements and the GCS coordination framework, which is composed by a set of classes that allow to the high level components to transparently control a group of mechanisms simultaneously.

Glucocorticoids and Metabolic Control.

PubMed

Magomedova, Lilia; Cummins, Carolyn L

2016-01-01

In response to stress, the central nervous system initiates a signaling cascade, which leads to the production of glucocorticoids (GCs). GCs act through the glucocorticoid receptor (GR) to coordinate the appropriate cellular response with the primary goal of mobilizing the storage forms of carbon precursors to generate a continuous glucose supply for the brain. Although GCs are critical for maintaining energy homeostasis, excessive GC stimulation leads to a number of undesirable side effects, including hyperglycemia, insulin resistance, fatty liver, obesity, and muscle wasting leading to severe metabolic dysfunction. Summarized below are the diverse metabolic roles of glucocorticoids in energy homeostasis and dysregulation, focusing specifically on glucose, lipid, and protein metabolism.

Glucocorticoid-induced changes in glucocorticoid receptor mRNA and protein expression in the human placenta as a potential factor for altering fetal growth and development.

PubMed

Bivol, Svetlana; Owen, Suzzanne J; Rose'Meyer, Roselyn B

2016-02-05

Glucocorticoids (GCs) control essential metabolic processes in virtually every cell in the body and play a vital role in the development of fetal tissues and organ systems. The biological actions of GCs are mediated via glucocorticoid receptors (GRs), the cytoplasmic transcription factors that regulate the transcription of genes involved in placental and fetal growth and development. Several experimental studies have demonstrated that fetal exposure to high maternal GC levels early in gestation is associated with adverse fetal outcomes, including low birthweight, intrauterine growth restriction and anatomical and structural abnormalities that may increase the risk of cardiovascular, metabolic and neuroendocrine disorders in adulthood. The response of the fetus to GCs is dependent on gender, with female fetuses becoming hypersensitive to changes in GC levels whereas male fetuses develop GC resistance in the environment of high maternal GCs. In this paper we review GR function and the physiological and pathological effects of GCs on fetal development. We propose that GC-induced changes in the placental structure and function, including alterations in the expression of GR mRNA and protein levels, may play role in inhibiting in utero fetal growth.

Microparticle-Mediated Delivery of BMP4 for Generation of Meiosis-Competent Germ Cells from Embryonic Stem Cells.

PubMed

Esfandiari, Fereshteh; Ashtiani, Mohammad Kazemi; Sharifi-Tabar, Mehdi; Saber, Maryam; Daemi, Hamed; Ghanian, Mohammad Hossein; Shahverdi, Abdolhossein; Baharvand, Hossein

2017-03-01

Producing meiosis-competent germ cells (GCs) from embryonic stem cells (ESCs) is essential for developing advanced therapies for infertility. Here, a novel approach is presented for generation of GCs from ESCs. In this regard, microparticles (MPs) have been developed from alginate sulfate loaded with bone morphogenetic protein 4 (BMP4). The results here show that BMP4 release from alginate sulfate MPs is significantly retarded by the sulfated groups compared to neat alginate. Then, BMP4-laden MPs are incorporated within the aggregates during differentiation of GCs from ESCs. It is observed that BMP4-laden MPs increase GC differentiation from ESCs at least twofold compared to the conventional soluble delivery method. Interestingly, following meiosis induction, Dazl, an intrinsic factor that enables GCs to enter meiosis, and two essential meiosis genes (Stra8 and Smc1b) are upregulated significantly in MP-induced aggregates compared to aggregates, which are formed by the conventional method. Together, these data show that controlled delivery of BMP4 during ESC differentiation into GC establish meiosis-competent GCs which can serve as an attractive GC source for reproductive medicine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

History and trends of bioactive glass-ceramics.

PubMed

Montazerian, Maziar; Dutra Zanotto, Edgar

2016-05-01

The interest around bioactive glass-ceramics (GCs) has grown significantly over the last two decades due to their appropriate biochemical and mechanical properties. The intense research effort in this field has led to some new commercial products for biomedical applications. This review article begins with the basic concepts of GC processing and development via controlled heat treatments of monolithic pieces or sinter-crystallization of powdered glasses. We then go on to describe the processing, properties, and applications of some commercial bioactive GCs and discuss selected valuable reported researches on several promising types of bioactive GCs. The article finishes with a section on open relevant research directions for bioactive GC development. © 2016 Wiley Periodicals, Inc.

Molecular Transducers from Roots Are Triggered in Arabidopsis Leaves by Root-Knot Nematodes for Successful Feeding Site Formation: A Conserved Post-Embryogenic De novo Organogenesis Program?

PubMed Central

Olmo, Rocío; Cabrera, Javier; Moreno-Risueno, Miguel A.; Fukaki, Hidehiro; Fenoll, Carmen; Escobar, Carolina

2017-01-01

Root-knot nematodes (RKNs; Meloidogyne spp.) induce feeding cells (giant cells; GCs) inside a pseudo-organ (gall) from still unknown root cells. Understanding GCs ontogeny is essential to the basic knowledge of RKN–plant interaction and to discover novel and effective control strategies. Hence, we report for the first time in a model plant, Arabidopsis, molecular, and cellular features concerning ectopic de novo organogenesis of RKNs GCs in leaves. RKNs induce GCs in leaves with irregular shape, a reticulated cytosol, and fragmented vacuoles as GCs from roots. Leaf cells around the nematode enter G2-M shown by ProCycB1;1:CycB1;1(NT)-GUS expression, consistent to multinucleated GCs. In addition, GCs nuclei present irregular and varied sizes. All these characteristics mentioned, being equivalent to GCs in root-galls. RKNs complete their life cycle forming a gall/callus-like structure in the leaf vascular tissues resembling auxin-induced callus with an auxin-response maxima, indicated by high expression of DR5::GUS that is dependent on leaf auxin-transport. Notably, induction of leaves calli/GCs requires molecular components from roots crucial for lateral roots (LRs), auxin-induced callus and root-gall formation, i.e., LBD16. Hence, LBD16 is a xylem pole pericycle specific and local marker in LR primordia unexpectedly induced locally in the vascular tissue of leaves after RKN infection. LBD16 is also fundamental for feeding site formation as RKNs could not stablish in 35S::LBD16-SRDX leaves, and likely it is also a conserved molecular hub between biotic and developmental signals in Arabidopsis either in roots or leaves. Moreover, RKNs induce the ectopic development of roots from leaf and root-galls, also formed in mutants compromised in LR formation, arf7/arf19, slr, and alf4. Therefore, nematodes must target molecular signatures to induce post-embryogenic de novo organogenesis through the LBD16 callus formation pathway partially different from those prevalent during normal LR development. PMID:28603536

Molecular Transducers from Roots Are Triggered in Arabidopsis Leaves by Root-Knot Nematodes for Successful Feeding Site Formation: A Conserved Post-Embryogenic De novo Organogenesis Program?

PubMed

Olmo, Rocío; Cabrera, Javier; Moreno-Risueno, Miguel A; Fukaki, Hidehiro; Fenoll, Carmen; Escobar, Carolina

2017-01-01

Root-knot nematodes (RKNs; Meloidogyne spp.) induce feeding cells (giant cells; GCs) inside a pseudo-organ (gall) from still unknown root cells. Understanding GCs ontogeny is essential to the basic knowledge of RKN-plant interaction and to discover novel and effective control strategies. Hence, we report for the first time in a model plant, Arabidopsis, molecular, and cellular features concerning ectopic de novo organogenesis of RKNs GCs in leaves. RKNs induce GCs in leaves with irregular shape, a reticulated cytosol, and fragmented vacuoles as GCs from roots. Leaf cells around the nematode enter G2-M shown by ProCycB1;1:CycB1;1(NT)-GUS expression, consistent to multinucleated GCs. In addition, GCs nuclei present irregular and varied sizes. All these characteristics mentioned, being equivalent to GCs in root-galls. RKNs complete their life cycle forming a gall/callus-like structure in the leaf vascular tissues resembling auxin-induced callus with an auxin-response maxima, indicated by high expression of DR5::GUS that is dependent on leaf auxin-transport. Notably, induction of leaves calli/GCs requires molecular components from roots crucial for lateral roots (LRs), auxin-induced callus and root-gall formation, i.e., LBD16. Hence, LBD16 is a xylem pole pericycle specific and local marker in LR primordia unexpectedly induced locally in the vascular tissue of leaves after RKN infection. LBD16 is also fundamental for feeding site formation as RKNs could not stablish in 35S::LBD16-SRDX leaves, and likely it is also a conserved molecular hub between biotic and developmental signals in Arabidopsis either in roots or leaves. Moreover, RKNs induce the ectopic development of roots from leaf and root-galls, also formed in mutants compromised in LR formation, arf7/arf19 , slr , and alf4 . Therefore, nematodes must target molecular signatures to induce post-embryogenic de novo organogenesis through the LBD16 callus formation pathway partially different from those prevalent during normal LR development.

Evidence for participation of GCS1 in fertilization of the starlet sea anemone Nematostella vectensis: Implication of a common mechanism of sperm–egg fusion in plants and animals

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

Ebchuqin, Eerdundagula; Yokota, Naoto; Yamada, Lixy

Highlights: • GCS1 is a sperm transmembrane protein that is essential for gamete fusion in flowering plants. • The GCS1 gene is present not only in angiosperms but also in unicellular organisms and animals. • NvGCS1 gene is expressed in the testis and GCS1 protein exists in sperm of a sea anemone. • Anti-GCS1 antibodies inhibited the fertilization, showing the participation in fertilization. - Abstract: It has been reported that GCS1 (Generative Cell Specific 1) is a transmembrane protein that is exclusively expressed in sperm cells and is essential for gamete fusion in flowering plants. The GCS1 gene is presentmore » not only in angiosperms but also in unicellular organisms and animals, implying the occurrence of a common or ancestral mechanism of GCS1-mediated gamete fusion. In order to elucidate the common mechanism, we investigated the role of GCS1 in animal fertilization using a sea anemone (Cnidaria), Nematostella vectensis. Although the existence of the GCS1 gene in N. vectensis has been reported, the expression of GCS1 in sperm and the role of GCS1 in fertilization are not known. In this study, we showed that the GCS1 gene is expressed in the testis and that GCS1 protein exists in sperm by in situ hybridization and proteomic analysis, respectively. Then we made four peptide antibodies against the N-terminal extracellular region of NvGCS1. These antibodies specifically reacted to NvGCS1 among sperm proteins on the basis of Western analysis and potently inhibited fertilization in a concentration-dependent manner. These results indicate that sperm GCS1 plays a pivotal role in fertilization, most probably in sperm–egg fusion, in a starlet sea anemone, suggesting a common gamete-fusion mechanism shared by eukaryotic organisms.« less

Wearing graduated compression stockings augments cutaneous vasodilation but not sweating during exercise in the heat.

PubMed

Fujii, Naoto; Nikawa, Toshiya; Tsuji, Bun; Kenny, Glen P; Kondo, Narihiko; Nishiyasu, Takeshi

2017-05-01

The activation of cutaneous vasodilation and sweating are essential to the regulation of core temperature during exercise in the heat. We assessed the effect of graduated compression induced by wearing stockings on cutaneous vasodilation and sweating during exercise in the heat (30°C). On two separate occasions, nine young males exercised for 45 min or until core temperature reached ~1.5°C above baseline resting while wearing either (1) stockings causing graduated compression (graduate compression stockings, GCS), or (2) loose-fitting stockings without compression (Control). Forearm vascular conductance was evaluated by forearm blood flow (venous occlusion plethysmography) divided by mean arterial pressure to estimate cutaneous vasodilation. Sweat rate was estimated using the ventilated capsule technique. Core and skin temperatures were measured continuously. Exercise duration was similar between conditions (Control: 42.2 ± 3.6 min vs. GCS: 42.2 ± 3.6 min, P  = 1.00). Relative to Control, GCS increased forearm vascular conductance during the late stages (≥30 min) of exercise (e.g., at 40 min, 15.6 ± 5.6 vs. 18.0 ± 6.0 units, P  = 0.01). This was paralleled by a greater sensitivity (23.1 ± 9.1 vs. 32.1 ± 15.0 units°C -1 , P  = 0.043) and peak level (14.1 ± 5.1 vs. 16.3 ± 5.7 units, P  = 0.048) of cutaneous vasodilation as evaluated from the relationship between forearm vascular conductance with core temperature. However, the core temperature threshold at which an increase in forearm vascular conductance occurred did not differ between conditions (Control: 36.9 ± 0.2 vs. GCS: 37.0 ± 0.3°C, P  = 0.13). In contrast, no effect of GCS on sweating was measured (all P  > 0.05). We show that the use of GCS during exercise in the heat enhances cutaneous vasodilation and not sweating. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Deconstructing the roles of glucocorticoids in adipose tissue biology and the development of central obesity.

PubMed

Lee, Mi-Jeong; Pramyothin, Pornpoj; Karastergiou, Kalypso; Fried, Susan K

2014-03-01

Central obesity is associated with insulin resistance and dyslipidemia. Thus, the mechanisms that control fat distribution and its impact on systemic metabolism have importance for understanding the risk for diabetes and cardiovascular disease. Hypercortisolemia at the systemic (Cushing's syndrome) or local levels (due to adipose-specific overproduction via 11β-hydroxysteroid dehydrogenase 1) results in the preferential expansion of central, especially visceral fat depots. At the same time, peripheral subcutaneous depots can become depleted. The biochemical and molecular mechanisms underlying the depot-specific actions of glucocorticoids (GCs) on adipose tissue function remain poorly understood. GCs exert pleiotropic effects on adipocyte metabolic, endocrine and immune functions, and dampen adipose tissue inflammation. GCs also regulate multiple steps in the process of adipogenesis. Acting synergistically with insulin, GCs increase the expression of numerous genes involved in fat deposition. Variable effects of GC on lipolysis are reported, and GC can improve or impair insulin action depending on the experimental conditions. Thus, the net effect of GC on fat storage appears to depend on the physiologic context. The preferential effects of GC on visceral adipose tissue have been linked to higher cortisol production and glucocorticoid receptor expression, but the molecular details of the depot-dependent actions of GCs are only beginning to be understood. In addition, increasing evidence underlines the importance of circadian variations in GCs in relationship to the timing of meals for determining their anabolic actions on the adipocyte. In summary, although the molecular mechanisms remain to be fully elucidated, there is increasing evidence that GCs have multiple, depot-dependent effects on adipocyte gene expression and metabolism that promote central fat deposition. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease. Copyright © 2013 Elsevier B.V. All rights reserved.

Motion control of nonlinear gantry crane system via priority-based fitness scheme in firefly algorithm

NASA Astrophysics Data System (ADS)

Jaafar, Hazriq Izzuan; Latif, Norfaneysa Abd; Kassim, Anuar Mohamed; Abidin, Amar Faiz Zainal; Hussien, Sharifah Yuslinda Syed; Aras, Mohd Shahrieel Mohd

2015-05-01

Advanced manufacturing technology made Gantry Crane System (GCS) is one of the suitable heavy machinery transporters and frequently employed in handling with huge materials. The interconnection of trolley movement and payload oscillation has a technical impact which needs to be considered. Once the trolley moves to the desired position with high speed, this will induce undesirable's payload oscillation. This frequent unavoidable load swing causes an efficiency drop, load damages and even accidents. In this paper, a new control strategy of Firefly Algorithm (FA) will be developed to obtain five optimal controller parameters (PID and PD) via Priority-based Fitness Scheme (PFS). Combinations of these five parameters are utilized for controlling trolley movement and minimizing the angle of payload oscillation. This PFS is prioritized based on steady-state error (SSE), overshoot (OS) and settling time (Ts) according to the needs and circumstances. Lagrange equation will be chosen for modeling and simulation will be conducted by using related software. Simulation results show that the proposed control strategy is efficient to control the trolley movement to the desired position and minimize the angle of payload oscillation.

Diurnal salivary cortisol measurement in the neurosurgical-surgical intensive care unit in critically ill acute trauma patients.

PubMed

Bartanusz, Viktor; Corneille, Michael G; Sordo, Salvador; Gildea, Marianne; Michalek, Joel E; Nair, Prakash V; Stewart, Ronald M; Jezova, Daniela

2014-12-01

Acute trauma patients represent a specific subgroup of the critically ill population due to sudden and dramatic changes in homeostasis and consequently extreme demands on the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. Salivary cortisol is an accepted surrogate for serum free cortisol in the assessment of HPA axis function. The purpose of this study was (1) to establish the feasibility of salivary cortisol measurement in acute trauma patients in the neurosurgical-surgical intensive care unit (NSICU), and (2) to determine the diurnal pattern of salivary cortisol in the acute phase after injury. Saliva from 50 acute trauma patients was prospectively collected twice a day at 6AM and 4PM during the first week after injury in the NSICU. Mean PM cortisol concentrations were significantly higher in subjects versus controls (p<0.001). Subjects failed to develop the expected PM versus AM decrease in cortisol concentration seen in controls (p=0.005). Salivary cortisol did not vary significantly with baseline Glasgow Coma Scale (GCS), Injury Severity Score, sex, injury type, ethnicity, or age. When comparing mean AM and PM salivary cortisol by GCS severity category (GCS ⩽8 and GCS >8) the AM salivary cortisol was significantly higher in patients with GCS ⩽8 (p=0.002). The results show a loss of diurnal cortisol variation in acute trauma patient in the NSICU during the first week of hospitalization. Patients with severe brain injury had higher morning cortisol levels than those with mild/moderate brain injury. Copyright © 2014 Elsevier Ltd. All rights reserved.

Seasonal Energetic Stress in a Tropical Forest Primate: Proximate Causes and Evolutionary Implications

PubMed Central

Foerster, Steffen; Cords, Marina; Monfort, Steven L.

2012-01-01

Animals facing seasonal variation in food availability experience selective pressures that favor behavioral adjustments such as migration, changes in activity, or shifts in diet. Eclectic omnivores such as many primates can process low-quality fallback food when preferred food is unavailable. Such dietary flexibility, however, may be insufficient to eliminate constraints on reproduction even for species that live in relatively permissive environments, such as moist tropical forests. Focusing on a forest-dwelling primate with a flexible diet (Cercopithecus mitis) we investigated whether females experience seasonal energetic stress and how it may relate to reproductive seasonality. We used fecal glucocorticoids (fGCs) as an indicator of energetic stress, controlling for the potentially confounding effects of social interactions and reproductive state. We modeled within-female fGC variation with General Linear Mixed Models, evaluating changes in feeding behavior and food availability as main effects. Regardless of reproductive state, fGCs increased when females shifted their diet towards fallback foods (mature leaves and other non-preferred items) and when they spent more time feeding, while fGCs decreased with feeding time on preferred items (insects, fruits, young leaves) and with the availability of young leaves. Changes in fruit availability had no general effects on fGCs, likely because fruits were sought out regardless of availability. As predicted, females in the energetically demanding stages of late pregnancy and early lactation showed greater increases in fGCs between periods of low versus high availability of fruits and young leaves than females in other reproductive states. Potential social stressors had no measurable effects on fGCs. Preliminary evidence suggests that seasonal energetic stress may affect the timing of infant independence from mothers and contribute to unusually long inter-birth intervals compared to closely related species of similar body size. Our findings highlight how the study of stress responses can provide insights into the proximate control of reproductive strategies. PMID:23209651

Seasonal energetic stress in a tropical forest primate: proximate causes and evolutionary implications.

PubMed

Foerster, Steffen; Cords, Marina; Monfort, Steven L

2012-01-01

Animals facing seasonal variation in food availability experience selective pressures that favor behavioral adjustments such as migration, changes in activity, or shifts in diet. Eclectic omnivores such as many primates can process low-quality fallback food when preferred food is unavailable. Such dietary flexibility, however, may be insufficient to eliminate constraints on reproduction even for species that live in relatively permissive environments, such as moist tropical forests. Focusing on a forest-dwelling primate with a flexible diet (Cercopithecus mitis) we investigated whether females experience seasonal energetic stress and how it may relate to reproductive seasonality. We used fecal glucocorticoids (fGCs) as an indicator of energetic stress, controlling for the potentially confounding effects of social interactions and reproductive state. We modeled within-female fGC variation with General Linear Mixed Models, evaluating changes in feeding behavior and food availability as main effects. Regardless of reproductive state, fGCs increased when females shifted their diet towards fallback foods (mature leaves and other non-preferred items) and when they spent more time feeding, while fGCs decreased with feeding time on preferred items (insects, fruits, young leaves) and with the availability of young leaves. Changes in fruit availability had no general effects on fGCs, likely because fruits were sought out regardless of availability. As predicted, females in the energetically demanding stages of late pregnancy and early lactation showed greater increases in fGCs between periods of low versus high availability of fruits and young leaves than females in other reproductive states. Potential social stressors had no measurable effects on fGCs. Preliminary evidence suggests that seasonal energetic stress may affect the timing of infant independence from mothers and contribute to unusually long inter-birth intervals compared to closely related species of similar body size. Our findings highlight how the study of stress responses can provide insights into the proximate control of reproductive strategies.

Facile Synthesis of Three-Dimensional Sandwiched MnO2@GCs@MnO2 Hybrid Nanostructured Electrode for Electrochemical Capacitors.

PubMed

Jian, Xian; Liu, Shiyu; Gao, Yuqi; Zhang, Wanli; He, Weidong; Mahmood, Asif; M Subramaniyam, Chandrasekar; Wang, Xiaolin; Mahmood, Nasir; Dou, Shi Xue

2017-06-07

Designable control over the morphology and structure of active materials is highly desirable for achieving high-performance devices. Here, we develop a facile microwave-assisted synthesis to decorate MnO 2 nanocrystals on three-dimensional (3D) graphite-like capsules (GCs) to obtain sandwich nanostructures (3D MnO 2 @GCs@MnO 2 ) as electrode materials for electrochemical capacitors (ECs). A templated growth of the 3D GCs was carried out via catalytic chemical vapor deposition and MnO 2 was decorated on the exterior and interior surfaces of the GC walls through microwave irradiation to build an engineered architecture with robust structural and morphological stability. The unique sandwiched architecture has a large interfacial surface area, and allows for rapid electrolyte diffusion through its hollow/open framework and fast electronic motion via the carbon backbone. Furthermore, the tough and rigid nature of GCs provides the necessary structural stability, and the strong synergy between MnO 2 and GCs leads to high electrochemical activity in both neutral (265.1 F/g at 0.5 A/g) and alkaline (390 F/g at 0.5 A/g) electrolytes. The developed hybrid exhibits stable capacitance up to 6000 cycles in 1 M Na 2 SO 4 . The hybrid is a potential candidate for future ECs and the present study opens up an effective avenue to design hybrid materials for various applications.

Up-regulated expression of WNT5a increases inflammation and oxidative stress via PI3K/AKT/NF-κB signaling in the granulosa cells of PCOS patients.

PubMed

Zhao, Yue; Zhang, Chunmei; Huang, Ying; Yu, Yang; Li, Rong; Li, Min; Liu, Nana; Liu, Ping; Qiao, Jie

2015-01-01

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder accompanied by chronic low-grade inflammation, but the molecular mechanism remains unclear. We investigated the action of WNT5a in the development of chronic inflammation in PCOS and the related molecular signaling pathways. This was a prospective study conducted at the Division of Reproduction Center, Peking University Third Hospital. A total of 35 PCOS patients and 87 control women who reported to the clinic for the in vitro procedure and the cause of marital infertility was male azoospermia were included. Mural granulosa cells (GCs) of 35 PCOS patients and 37 controls were collected during oocyte retrieval and gene expression was analyzed. The human KGN cells and mural GCs from 50 control subjects (six to eight samples were pooled together for each experiment) were cultured in vitro. The regulation of inflammation and oxidative stress was confirmed by quantitative PCR, flow-cytometric assay, and dual-luciferase reporter assay after inflammatory stimuli or WNT5a overexpression. Relevant signaling pathways were identified using specific inhibitors. Our data demonstrate significantly elevated WNT5a expression in the mural GCs of PCOS patients compared with the controls. Lipopolysaccharide stimulation increased WNT5a expression in KGN cells and mural GCs, and BAY-117082 and pyrrolidinedithiocarbamic acid [nuclear factor-κB (NF-κB) inhibitor] treatments suppressed WNT5a mRNA below the control level. WNT5a overexpression also enhanced the expression of inflammation-related genes and increased intracellular reactive oxygen species, whereas both BAY-117082 and LY-294002 (phosphatidylinositol 3-kinase inhibitor) significantly inhibited WNT5a-induced inflammation and oxidative stress. WNT5a acts as a proinflammatory factor in human ovarian GCs. The up-regulated expression of WNT5a in PCOS increases inflammation and oxidative stress predominantly via the phosphatidylinositol 3-kinase/AKT/NF-κB signaling pathway. The proinflammatory cytokines induced might further enhance WNT5a expression via NF-κB-dependent regulation, indicating a novel regulatory system for chronic inflammation in PCOS.

Effects of luteinizing hormone and human chorionic gonadotropin on corpus luteum cells in a spheroid cell culture system.

PubMed

Walz, A; Keck, C; Weber, H; Kissel, C; Pietrowski, D

2005-09-01

The human corpus luteum (CL) is a highly vascularized, temporarily active endocrine gland and consists mainly of granulosa cells (GCs), theca cells (TCs), and endothelial cells (ECs). Its cyclic growth and development takes place under the influence of gonadotropic hormones. If pregnancy does occur, human chorionic gonadotropin (hCG) takes over the function of luteinizing hormone (LH) and, in contrast to LH, extends the functional life span of the CL. In this study, we investigated the effects of hCG and LH in a spheroidal cell culture model of CL development. Our data indicate that GCs secrete factors under the control of hCG that increase sprout formation of EC-spheroids. We demonstrate that the most prominent of these factors is VEGF-A. Furthermore, we found that both LH and hCG decrease sprout formation of GC-spheroids. After forming EC-GC coculture spheroids and consequently bringing GCs and ECs in close contact, sprouting increased under the influence of hCG, however not under LH. These experiments provide evidence for an hCG dependent functional switch in the GCs after coming in contact with ECs. Moreover, it demonstrates the considerably different effects of hCG and LH on GCs although their signaling is transmitted via the same receptor.

Analyzing Sliding Stability of Structures Using the Modified Computer Program GWALL. Revision,

DTIC Science & Technology

1983-11-01

R136 954 RNRLYZING SLIDING STRBILITY OF STRUCTURES USING THE i/i MODIFIED COMPUTER PRO..(U) ARMY ENGINEER WATERRYS EXPERIMENT STATION VICKSBURG MS...GWALL and/or the graphics software package, Graphics Compati- bility System (GCS). Input Features 4. GWALL is very easy to use because it allows the...Prepared Data File 9. Time-sharing computer systems do not always respond quickly to the userts commands, especially when there are many users

Which score should be used in intubated patients’ Glasgow coma scale or full outline of unresponsiveness?

PubMed Central

Gorji, Mohammad Ali Heidari; Gorji, Ali Morad Heidari; Hosseini, Seyed Hossein

2015-01-01

Background and Aims: Today Glasgow coma scale (GCS) is the most well-known and common score for evaluation of the level of consciousness and outcome predict after traumatic brain injuries in the world. Regarding to some advantages of the full outline of unresponsiveness (FOUR) score over GCS in intubated patients, we’re going to compare the precision of these two scores in predicting the outcome predict in intubated patients. Methods: This research was a diagnostic-based study, which was conducted prospectively on 80 patients with Traumatic brain injury who were intubated and admitted to Intensive Care Unit (ICU) of Educational Hospitals of Mazandaran University of Medical Science during February 2013 to August 2013. The scores of FOUR and GCS were measured by the researcher in the first 24 h of admission in ICU. The information's recorded in the check list including the mortality rate of early and late inside of the hospital interred to excel. The findings were analyzed using SPSS software, through descriptive statistics and regression logistic. Results: The results showed of 80 patients 21 patients (20%) were female and 59 patients (80%) were male. The age average of the samples was 33.80 ± 12.60 ranging from 16 to 60 years old. 21 patients (26.2%) died during treatment. Of 21 patients, 15 patients died during first 14 days (18.7%) and 6 patients died after 14 years (7.5%). The area under curve (AUC) of FOUR score in early mortality was 0.90 (C1 = 0.95, 0.88–0.90). The amount AUC for GCS was 0.80 (C1 = 0.95, 0.78–0.84), which in delayed mortality it was ordered as 0.86 (C1 = 0.95, 0.84–0.90) and 0.89 (C1 = 0.95, 0.78–0.88). Conclusion: The research results indicated that FOUR score is more exact and more practical in intubated patients regarding lack of verbal response factor in early mortality prediction in GCS. Hence, it is recommended for health professionals to use the FOUR score to predict the early outcome of intubated patients with traumatic brain injuries. PMID:26097814

Selective vulnerability of dentate granule cells prior to amyloid deposition in PDAPP mice: digital morphometric analyses.

PubMed

Wu, Chi-Cheng; Chawla, Faisal; Games, Dora; Rydel, Russell E; Freedman, Stephen; Schenk, Dale; Young, Warren G; Morrison, John H; Bloom, Floyd E

2004-05-04

Increasing evidence from mouse models of Alzheimer's disease shows that overexpression of a mutant form of the amyloid precursor protein (APP) and its product, beta-amyloid peptide, initiate pathological changes before amyloid deposition. To evaluate the cytological basis for one of these early changes, namely reduced volume of the dentate gyrus (DG), we have used high-throughput diOlistic cell loading and 3D neuronal reconstruction to investigate potential dendritic pathology of granule cells (GCs) in 90-day-old PDAPP mice. Labeled GCs from fixed hippocampal slices were selected randomly and imaged digitally by using confocal laser-scanning microscopy. The dendritic complexity of GCs was quantified according to subordinate morphological parameters, including soma position within the granule cell layer (superficial versus deep) and topographic location within the DG (dorsal versus ventral blade) along the anterior-posterior hippocampal axis. Initial analysis, which included all sampled GC types, revealed a 12% reduction of total dendritic length in PDAPP mice compared with littermate controls. Further analysis, performed with refined subgroups, found that superficially located GCs in the dorsal blade were profoundly altered, exhibiting a 23% loss in total dendritic length, whereas neurons in the ventral blade were unaffected. Superficial GCs were particularly vulnerable (a 32% reduction) in the posterior region of the DG. Furthermore, the dendritic reductions of this select group were uniformly localized within middle-to-outer portions of the dentate molecular layer. We conclude that substantial dendritic pathology is evident in 90-day-old PDAPP mice for a spatially defined subset of GCs well before amyloid accumulation occurs.

Selective vulnerability of dentate granule cells prior to amyloid deposition in PDAPP mice: Digital morphometric analyses

PubMed Central

Wu, Chi-Cheng; Chawla, Faisal; Games, Dora; Rydel, Russell E.; Freedman, Stephen; Schenk, Dale; Young, Warren G.; Morrison, John H.; Bloom, Floyd E.

2004-01-01

Increasing evidence from mouse models of Alzheimer's disease shows that overexpression of a mutant form of the amyloid precursor protein (APP) and its product, β-amyloid peptide, initiate pathological changes before amyloid deposition. To evaluate the cytological basis for one of these early changes, namely reduced volume of the dentate gyrus (DG), we have used high-throughput diOlistic cell loading and 3D neuronal reconstruction to investigate potential dendritic pathology of granule cells (GCs) in 90-day-old PDAPP mice. Labeled GCs from fixed hippocampal slices were selected randomly and imaged digitally by using confocal laser-scanning microscopy. The dendritic complexity of GCs was quantified according to subordinate morphological parameters, including soma position within the granule cell layer (superficial versus deep) and topographic location within the DG (dorsal versus ventral blade) along the anterior-posterior hippocampal axis. Initial analysis, which included all sampled GC types, revealed a 12% reduction of total dendritic length in PDAPP mice compared with littermate controls. Further analysis, performed with refined subgroups, found that superficially located GCs in the dorsal blade were profoundly altered, exhibiting a 23% loss in total dendritic length, whereas neurons in the ventral blade were unaffected. Superficial GCs were particularly vulnerable (a 32% reduction) in the posterior region of the DG. Furthermore, the dendritic reductions of this select group were uniformly localized within middle-to-outer portions of the dentate molecular layer. We conclude that substantial dendritic pathology is evident in 90-day-old PDAPP mice for a spatially defined subset of GCs well before amyloid accumulation occurs. PMID:15118092

Designing on-Board Data Handling for EDF (Electric Ducted Fan) Rocket

NASA Astrophysics Data System (ADS)

Mulyana, A.; Faiz, L. A. A.

2018-02-01

The EDF (Electric Ducted Fan) rocket to launch requires a system of monitoring, tracking and controlling to allow the rocket to glide properly. One of the important components in the rocket is OBDH (On-Board Data Handling) which serves as a medium to perform commands and data processing. However, TTC (Telemetry, Tracking, and Command) are required to communicate between GCS (Ground Control Station) and OBDH on EDF rockets. So the design control system of EDF rockets and GCS for telemetry and telecommand needs to be made. In the design of integrated OBDH controller uses a lot of electronics modules, to know the behavior of rocket used IMU sensor (Inertial Measurement Unit) in which consist of 3-axis gyroscope sensor and Accelerometer 3-axis. To do tracking using GPS, compass sensor as a determinant of the direction of the rocket as well as a reference point on the z-axis of gyroscope sensor processing and used barometer sensors to measure the height of the rocket at the time of glide. The data can be known in real-time by sending data through radio modules at 2.4 GHz frequency using XBee-Pro S2B to GCS. By using windows filter, noises can be reduced, and it used to guarantee monitoring and controlling system can work properly.

Simplifying the use of prognostic information in traumatic brain injury. Part 1: The GCS-Pupils score: an extended index of clinical severity.

PubMed

Brennan, Paul M; Murray, Gordon D; Teasdale, Graham M

2018-06-01

OBJECTIVE Glasgow Coma Scale (GCS) scores and pupil responses are key indicators of the severity of traumatic brain damage. The aim of this study was to determine what information would be gained by combining these indicators into a single index and to explore the merits of different ways of achieving this. METHODS Information about early GCS scores, pupil responses, late outcomes on the Glasgow Outcome Scale, and mortality were obtained at the individual patient level by reviewing data from the CRASH (Corticosteroid Randomisation After Significant Head Injury; n = 9,045) study and the IMPACT (International Mission for Prognosis and Clinical Trials in TBI; n = 6855) database. These data were combined into a pooled data set for the main analysis. Methods of combining the Glasgow Coma Scale and pupil response data varied in complexity from using a simple arithmetic score (GCS score [range 3-15] minus the number of nonreacting pupils [0, 1, or 2]), which we call the GCS-Pupils score (GCS-P; range 1-15), to treating each factor as a separate categorical variable. The content of information about patient outcome in each of these models was evaluated using Nagelkerke's R 2 . RESULTS Separately, the GCS score and pupil response were each related to outcome. Adding information about the pupil response to the GCS score increased the information yield. The performance of the simple GCS-P was similar to the performance of more complex methods of evaluating traumatic brain damage. The relationship between decreases in the GCS-P and deteriorating outcome was seen across the complete range of possible scores. The additional 2 lowest points offered by the GCS-Pupils scale (GCS-P 1 and 2) extended the information about injury severity from a mortality rate of 51% and an unfavorable outcome rate of 70% at GCS score 3 to a mortality rate of 74% and an unfavorable outcome rate of 90% at GCS-P 1. The paradoxical finding that GCS score 4 was associated with a worse outcome than GCS score 3 was not seen when using the GCS-P. CONCLUSIONS A simple arithmetic combination of the GCS score and pupillary response, the GCS-P, extends the information provided about patient outcome to an extent comparable to that obtained using more complex methods. The greater range of injury severities that are identified and the smoothness of the stepwise pattern of outcomes across the range of scores may be useful in evaluating individual patients and identifying patient subgroups. The GCS-P may be a useful platform onto which information about other key prognostic features can be added in a simple format likely to be useful in clinical practice.

Factors influencing pediatric Injury Severity Score and Glasgow Coma Scale in pediatric automobile crashes: results from the Crash Injury Research Engineering Network.

PubMed

Ehrlich, Peter F; Brown, J Kristine; Sochor, Mark R; Wang, Stewart C; Eichelberger, Martin E

2006-11-01

Motor vehicle crashes account for more than 50% of pediatric injuries. Triage of pediatric patients to appropriate centers can be based on the crash/injury characteristics. Pediatric motor vehicle crash/injury characteristics can be determined from an in vitro laboratory using child crash dummies. However, to date, no detailed data with respect to outcomes and crash mechanism have been presented with a pediatric in vivo model. The Crash Injury Research Engineering Network is comprised of 10 level 1 trauma centers. Crashes were examined with regard to age, crash severity (DeltaV), crash direction, restraint use, and airbag deployment. Multiple logistic regression analysis was performed with Injury Severity Score (ISS) and Glasgow Coma Scale (GCS) as outcomes. Standard age groupings (0-4, 5-9, 10-14, and 15-18) were used. The database is biases toward a survivor population with few fatalities. Four hundred sixty-one motor vehicle crashes with 2500 injuries were analyzed (242 boys, 219 girls). Irrespective of age, DeltaV > 30 mph resulted in increased ISS and decreased GCS (eg, for 0-4 years, DeltaV < 30: ISS = 10, GCS = 13.5 vs DeltaV > 30: ISS = 19.5, GCS = 10.6; P < .007, < .002, respectively). Controlling for DeltaV, children in lateral crashes had increased ISS and decreased GCS versus those in frontal crashes. Airbag deployment was protective for children 15 to 18 years old and resulted in a lower ISS and higher GCS (odds ratio, 2.1; 95% confidence interval, 0.9-4.6). Front-seat passengers suffered more severe (ISS > 15) injuries than did backseat passengers (odds ratio, 1.7; 95% confidence interval, 0.7-3.4). A trend was noted for children younger than 12 years sitting in the front seat to have increased ISS and decreased GCS with airbag deployment but was limited by case number. A reproducible pattern of increased ISS and lower GCS characterized by high severity, lateral crashes in children was noted. Further analysis of the specific injuries as a function and the crash characteristic can help guide management and prevention strategies.

Glucocorticosteroids associated with a decreased risk of psychosis.

PubMed

Laan, Wijnand; Smeets, Hugo; de Wit, Niek J; Kahn, René S; Grobbee, Diederick E; Burger, Huibert

2009-06-01

The hypothesis that chronic inflammation may play a role in psychosis receives increasing attention. In this study, we aim to investigate whether the use of steroidal anti-inflammatory drugs is associated with a decreased risk of psychosis.A longitudinal nested case-control study was performed investigating the association of glucocorticosteroid (GCS) consumption with a new diagnosis of a psychotic disorder. Significantly reduced odds ratios of 0.52 (95% confidence interval, 0.36-0.75) were found for GCS in men only (odds ratio in women, 0.84 [95% confidence interval, 0.590-1.20]). Similar risk reductions were present for the inhaled and systemic GCSs. A dose-response relationship was present. Our finding of an inverse relation between GCS consumption and new psychotic episodes may promote further research into inflammation in schizophrenia.

Risk factors of postictal generalized EEG suppression in generalized convulsive seizures.

PubMed

Alexandre, Veriano; Mercedes, Blanca; Valton, Luc; Maillard, Louis; Bartolomei, Fabrice; Szurhaj, William; Hirsch, Edouard; Marchal, Cécile; Chassoux, Francine; Petit, Jérôme; Crespel, Arielle; Nica, Anca; Navarro, Vincent; Kahane, Philippe; De Toffol, Bertrand; Thomas, Pierre; Rosenberg, Sarah; Denuelle, Marie; Jonas, Jacques; Ryvlin, Philippe; Rheims, Sylvain

2015-11-03

To identify the clinical determinants of occurrence of postictal generalized EEG suppression (PGES) after generalized convulsive seizures (GCS). We reviewed the video-EEG recordings of 417 patients included in the REPO2MSE study, a multicenter prospective cohort study of patients with drug-resistant focal epilepsy. According to ictal semiology, we classified GCS into 3 types: tonic-clonic GCS with bilateral and symmetric tonic arm extension (type 1), clonic GCS without tonic arm extension or flexion (type 2), and GCS with unilateral or asymmetric tonic arm extension or flexion (type 3). Association between PGES and person-specific or seizure-specific variables was analyzed after correction for individual effects and the varying number of seizures. A total of 99 GCS in 69 patients were included. Occurrence of PGES was independently associated with GCS type (p < 0.001) and lack of early administration of oxygen (p < 0.001). Odds ratio (OR) for GCS type 1 in comparison with GCS type 2 was 66.0 (95% confidence interval [CI 5.4-801.6]). In GCS type 1, risk of PGES was significantly increased when the seizure occurred during sleep (OR 5.0, 95% CI 1.2-20.9) and when oxygen was not administered early (OR 13.4, 95% CI 3.2-55.9). The risk of PGES dramatically varied as a function of GCS semiologic characteristics. Whatever the type of GCS, occurrence of PGES was prevented by early administration of oxygen. © 2015 American Academy of Neurology.

Novel aspects of glucocorticoid actions.

PubMed

Uchoa, E T; Aguilera, G; Herman, J P; Fiedler, J L; Deak, T; de Sousa, M B C

2014-09-01

Normal hypothalamic-pituitary-adrenal (HPA) axis activity leading to the rhythmic and episodic release of adrenal glucocorticoids (GCs) is essential for body homeostasis and survival during stress. Acting through specific intracellular receptors in the brain and periphery, GCs regulate behaviour, as well as metabolic, cardiovascular, immune and neuroendocrine activities. By contrast to chronic elevated levels, circadian and acute stress-induced increases in GCs are necessary for hippocampal neuronal survival and memory acquisition and consolidation, as a result of the inhibition of apoptosis, the facilitation of glutamatergic neurotransmission and the formation of excitatory synapses, and the induction of immediate early genes and dendritic spine formation. In addition to metabolic actions leading to increased energy availability, GCs have profound effects on feeding behaviour, mainly via the modulation of orexigenic and anorixegenic neuropeptides. Evidence is also emerging that, in addition to the recognised immune suppressive actions of GCs by counteracting adrenergic pro-inflammatory actions, circadian elevations have priming effects in the immune system, potentiating acute defensive responses. In addition, negative-feedback by GCs involves multiple mechanisms leading to limited HPA axis activation and prevention of the deleterious effects of excessive GC production. Adequate GC secretion to meet body demands is tightly regulated by a complex neural circuitry controlling hypothalamic corticotrophin-releasing hormone (CRH) and vasopressin secretion, which are the main regulators of pituitary adrenocorticotrophic hormone (ACTH). Rapid feedback mechanisms, likely involving nongenomic actions of GCs, mediate the immediate inhibition of hypothalamic CRH and ACTH secretion, whereas intermediate and delayed mechanisms mediated by genomic actions involve the modulation of limbic circuitry and peripheral metabolic messengers. Consistent with their key adaptive roles, HPA axis components are evolutionarily conserved, being present in the earliest vertebrates. An understanding of these basic mechanisms may lead to novel approaches for the development of diagnostic and therapeutic tools for disorders related to stress and alterations of GC secretion. © 2014 British Society for Neuroendocrinology.

Wilms' Tumor 1 Overexpression in Granulosa Cells Is Associated with Polycystic Ovaries in Polycystic Ovary Syndrome Patients.

PubMed

Wang, Qun; Huang, Tao; Shu, Xin; Zhao, Shi-Gang; Liang, Yu; Muhammad, Tahir; Gao, Fei; Zhao, Han; Liu, Hong-Bin

2018-01-01

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by chronic ovulatory dysfunction, hyperandrogenism, and polycystic ovaries. Wilms' tumor 1 (WT1) encoding a transcription factor involved in the differentiation of granulosa cells (GCs) regulates androgen receptor in the development of male genitalia. However, the expression pattern and possible role of WT1 in ovaries of PCOS patients are still unknown. GCs from 95 PCOS patients (PCOS group) and 62 healthy controls (control group) were isolated. The expression of WT1 in GCs was quantified using the reverse transcription-polymerase chain reaction. The correlation between WT1 expression and clinical characteristics was evaluated in PCOS patients. WT1 expression was increased in PCOS patients compared with the normal controls. The expression of WT1 was moderately correlated with testosterone (r = 0.334, p = 0.001) and luteinizing hormone (r = 0.357, p = 0.001) levels and the antral follicle counts (r = 0.337, p = 0.001). Our study provided novel insights into the relationship between hyperandrogenism and polycystic ovaries of PCOS and WT1. © 2018 S. Karger AG, Basel.

Roles of methyltrienolone (R1881) in AKTs and AR expression patterns of cultured granulosa-lutein cells.

PubMed

Nekoonam, Saeid; Naji, Mohammad; Mortezaee, Keywan; Amidi, Fardin

2018-05-11

AR-mediated androgen signaling plays a key role in female reproductive system. Granulosa-lutein cells (GCs) are the main sites for expression of androgen receptor (AR). There is also a close relation between AKT signaling and AR. Here, we assayed the role for a synthetic AR ligand methyltrienolone (R1881) in expressions of AKTs and AR. Controlled ovarian hyperstimulation (COH) was performed in 20 normal women. Mural GCs were isolated by filtration method, cultured, and passaged. Then, the cells were starved for 48 h with 10% charcoal stripped FBS. The cells were then treated with R1881, bicalutamide (AR blocker), LY294002 (PI3K/AKT pathway blocker), and combination of them for 48 h. Finally, GCs were evaluated for quantitative real-time PCR analysis of AKT1, AKT2, AKT3, and AR, and also Western blot assessment of total AKT and phosphorylated AKT (p-AKT) [Ser473 and Thr308]. Addition of R1881 to the GCs culture showed high expressions of AKT1, AKT2, and AKT3 (P ≤ 0.05 vs LY294002 group and bicalutamide group). Expressions of AKT1 and AKT2 were decreased in the GCs under exposure to bicalutamide or LY294002 (P ≤ 0.05 vs R1881). AKT1, AKT2, and AKT3 showed decreased rates of expressions in the LY294002 + bicalutamide group (P ≤ 0.05 vs R1881). AR, total AKT and p-AKT showed no significant differences between groups. Our findings indicate that 46 h exposure with R1881 could affect AKTs expressions in the GCs of pre-ovulatory phase, but it cannot promote AR expression and AKTs activation. © 2018 Wiley Periodicals, Inc.

Analysis of Giant-nucleated Cell Formation Following X-ray and Proton Irradiations

NASA Astrophysics Data System (ADS)

Almahwasi, Ashraf Abdu

Radiation-induced genetic instability has been observed in survivors of irradiated cancerous and normal cells in vitro and in vivo and has been determined in different forms, such as delayed cell death, chromosomal aberration or mutation. A well defined and characterized normal human-diploid AG1522 fibroblast cell line was used to study giant-nucleated cell (GCs) formation as the ultimate endpoint of this research. The average nuclear cross-sectional areas of the AG1522 cells were measured in mum2. The doubling time required by the AG1522 cells to divide was measured. The potential toxicity of the Hoechst dye at a working concentration on the live AG1522 cells was assessed. The yield of giant cells was determined at 7, 14 and 21 days after exposure to equivalent clinical doses of 0.2, 1 or 2 Gy of X-ray or proton irradiation. Significant differences were found to exist between X-ray or proton irradiation when compared with sham-irradiated control populations. The frequency of GCs induced by X-rays was also compared to those formed in proton irradiated cultures. The results confirm that 1 Gy X-rays are shown to induce higher rates of mitotically arrested GCs, increasing continually over time up to 21 days post-irradiation. The yield of GCs was significantly greater (10%) compared to those formed in proton populations (2%) 21 days postirradiation. The GCs can undergo a prolonged mitotic arrest that significantly increases the length of cell cycle. The arrest of GCs at the mitotic phase for longer periods of time might be indicative of a strategy for cell survival, as it increases the time available for DNA repair and enables an alternative route to division for the cells. However, the reduction in their formation 21 days after both types of radiation might favour GCs formation, ultimately contributing to carcinogenesis or cancer therapy resistance. The X-ray experiments revealed a dose-dependent increase in the GCs up to 14 days after irradiation. Although the proton irradiation was less efficient in producing GCs, their frequency was elevated in a dose-dependent manner 7 days after irradiation, with persistent expression of nuclear deformity as an indicator of genetic instability. In addition to the quantification of the GCs, the proliferation of a small fraction of giant cells formed at 14 days after 0.2 Gy of proton irradiation was observed to divide into asymmetrical, normal-sized daughter cells. These results might have important implications in evaluating risk estimates, or could act as a potential radioprotective assay for a dose-limiting parameter for delayed effects in healthy tissues during radiation therapy treatment.

Concept and realization of unmanned aerial system with different modes of operation

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

Czyba, Roman; Szafrański, Grzegorz; Janusz, Wojciech

2014-12-10

In this paper we describe the development process of unmanned aerial system, its mechanical components, electronics and software solutions. During the stage of design, we have formulated some necessary requirements for the multirotor vehicle and ground control station in order to build an optimal system which can be used for the reconnaissance missions. Platform is controlled by use of the ground control station (GCS) and has possibility of accomplishing video based observation tasks. In order to fulfill this requirement the on-board payload consists of mechanically stabilized camera augmented with machine vision algorithms to enable object tracking tasks. Novelty of themore » system are four modes of flight, which give full functionality of the developed UAV system. Designed ground control station is consisted not only of the application itself, but also a built-in dedicated components located inside the chassis, which together creates an advanced UAV system supporting the control and management of the flight. Mechanical part of quadrotor is designed to ensure its robustness while meeting objectives of minimizing weight of the platform. Finally the designed electronics allows for implementation of control and estimation algorithms without the needs for their excessive computational optimization.« less

The FOUR score and GCS as predictors of outcome after traumatic brain injury.

PubMed

McNett, Molly; Amato, Shelly; Gianakis, Anastasia; Grimm, Dawn; Philippbar, Sue Ann; Belle, Josie; Moran, Cristina

2014-08-01

The Glasgow Coma Scale (GCS) is a routine component of a neurological exam for critically ill traumatic brain injury (TBI) patients, yet has been criticized for not accurately depicting verbal status among intubated patients or including brain stem reflexes. Preliminary research on the Full Outline of UnResponsiveness (FOUR) Scale suggests it overcomes these limitations. Research is needed to determine correlations with patient outcomes. The aims of this study were to: (1) examine correlations between 24 and 72 h FOUR and GCS scores and functional/cognitive outcomes; (2) determine relationship between 24 and 72 h FOUR scores and mortality. Prospective cohort study. Data gathered on adult TBI patients at a Level I trauma center. FOUR scores assigned at 24, 72 h. Functional outcome measured by functional independence measure scores at rehabilitation discharge; cognitive status measured by Weschler Memory Scale scores 3 months post-injury. n = 136. Mean age 53.1. 72 h FOUR and GCS scores correlated with functional outcome (r s = 0.34, p = 0.05; r s = 0.39, p = 0.02), but not cognitive status. Receiver operating characteristic curves were comparable for FOUR and GCS at 24 and 72 h for functional status (24 h FOUR, GCS = 0.625, 0.602, respectively; 72 h FOUR, GCS = 0.640, 0.688), cognitive status (24 h FOUR, GCS = 0.703, 0.731; 72 h FOUR, GCS = 0.837, 0.674), and mortality (24 h FOUR, GCS = 0.913, 0.935; 72 h FOUR, GCS = 0.837, 0.884). FOUR is comparable to GCS in terms of predictive ability for functional status, cognitive outcome 3 months post-injury, and in-hospital mortality.

Delayed coupling to feedback inhibition during a critical period for the integration of adult-born granule cells

PubMed Central

Temprana, Silvio G.; Mongiat, Lucas A.; Yang, Sung M.; Trinchero, Mariela F.; Alvarez, Diego D.; Kropff, Emilio; Giacomini, Damiana; Beltramone, Natalia; Lanuza, Guillermo M.; Schinder, Alejandro F.

2014-01-01

SUMMARY Developing granule cells (GCs) of the adult dentate gyrus undergo a critical period of enhanced activity and synaptic plasticity before becoming mature. The impact of developing GCs on the activity of preexisting dentate circuits remains unknown. Here we combine optogenetics, acute slice electrophysiology, and in vivo chemogenetics to activate GCs at different stages of maturation to study the recruitment of local target networks. We show that immature (four-week-old) GCs can efficiently drive distal CA3 targets, but poorly activate proximal interneurons responsible for feedback inhibition (FBI). As new GCs transition towards maturity, they reliably recruit GABAergic feedback loops that restrict spiking of neighbor GCs, a mechanism that would promote sparse coding. Such inhibitory loop impinges only weakly in new cohorts of young GCs. A computational model reveals that the delayed coupling of new GCs to FBI could be crucial to achieve a fine-grain representation of novel inputs in the dentate gyrus. PMID:25533485

Delayed coupling to feedback inhibition during a critical period for the integration of adult-born granule cells.

PubMed

Temprana, Silvio G; Mongiat, Lucas A; Yang, Sung M; Trinchero, Mariela F; Alvarez, Diego D; Kropff, Emilio; Giacomini, Damiana; Beltramone, Natalia; Lanuza, Guillermo M; Schinder, Alejandro F

2015-01-07

Developing granule cells (GCs) of the adult dentate gyrus undergo a critical period of enhanced activity and synaptic plasticity before becoming mature. The impact of developing GCs on the activity of preexisting dentate circuits remains unknown. Here we combine optogenetics, acute slice electrophysiology, and in vivo chemogenetics to activate GCs at different stages of maturation to study the recruitment of local target networks. We show that immature (4-week-old) GCs can efficiently drive distal CA3 targets but poorly activate proximal interneurons responsible for feedback inhibition (FBI). As new GCs transition toward maturity, they reliably recruit GABAergic feedback loops that restrict spiking of neighbor GCs, a mechanism that would promote sparse coding. Such inhibitory loop impinges only weakly in new cohorts of young GCs. A computational model reveals that the delayed coupling of new GCs to FBI could be crucial to achieve a fine-grain representation of novel inputs in the dentate gyrus. Copyright © 2015 Elsevier Inc. All rights reserved.

Music therapy for coma patients: preliminary results.

PubMed

Sun, J; Chen, W

2015-04-01

The application of quantitative EEG (δ+θ/α+β value) and GCS value to evaluate the role of music therapy for traumatic brain injury coma patients. Forty patients of traumatic brain injury coma were selected to meet the inclusion criteria. Twenty cases were selected for the rehabilitation, neurology and neurosurgery ward, whose families could actively cooperate with, and the patients could receive a long-term fixed nursing staff with formal music therapy (music group). Twenty cases were in the intensive care unit of the rehabilitation, neurology and neurosurgery ward. Their families members cooperated poorly, had often changing nursing staff, and without a formal music therapy (control group). After a one monthe follow up, the GCS value and quantitative EEG (δ+θ/α+β value) were compared between the two groups. Between the two groups, except for the presence or absence of formal music therapy, the rest of treatment had no significant difference and was matched by age, gender, and injury types. In 40 cases of traumatic brain injury patients, the GCS value increased in the music group after treatment when compared to the control group. The difference between the two groups was significant (p < 0.05). The quantitative EEG value (δ+θ/α+β value) of music group values were decreased after treatment, and the difference was significant compared with the control group (p < 0.05). Through the quantitative EEG (δ+θ/α+β value) and the GCS observation score, music therapy in patients with craniocerebral trauma coma has obviously an effect on promoting to regain consciousness. The quantitative EEG (δ+θ/α+β value) can be used as an objective index to evaluate the state of brain function.

Diagnostic and Prognostic Capability of Newer Magnetic Resonance Imaging Brain Sequences in Diffuse Axonal Injury Patient.

PubMed

Bansal, Mayank; Sinha, Virendra Deo; Bansal, Juhi

2018-01-01

Diffuse axonal injury is one of the major causes of unconsciousness, profound neurologic deficits and persistent vegetative state after head trauma. In recent years, MR imaging has been gaining popularity as an adjunctive imaging method in patients with DAI. Our study aims to assess the relative diagnostic and prognostic capability of various MRI sequences. Retrospective observational study done in 1 year duration on 30 DAI patients. Clinical assessment done with GCS at admission and GOS at 6 month. MRI Brain FLAIR, DWI, T2*GRE AND SWI sequences taken. DAI grade were evaluated for different MRI sequences. Prognosis was correlated to total number of lesion/locations and DAI grade of patients. Statistical analysis was done using SPSS Statistical software (ver.20.0.0) and XL-Stat and ANOVA one way test, post hoc test (Turkey test) and Chi square test. We studied 30 male patients, mean age 32.57±8.72 ranges. The commonest mode of injury is RTA-80%, fall-16% followed by assault-3.33%. Out of 30 patients, 17 patients (56.67%) had GCS <=8, 13 patients (43.33%) had GCS between 9 and 12 and no patient had a GCS score between 13 and 15. The mean GCS score was 8.47±1.50. At a 6 month follow up, out of a total of 30 patients, 2 patients (6.66%) expired (GOS-1), 3 patients (10%) remained in persistent vegetative state (GOS-2), 11 patients (36.67%) and 10 patients (33.33%) were found to be severely (GOS-3) and moderately (GOS-4) disabled respectively and 4 patients (13.33%) showed good recovery (GOS-5). Mean GOS is 3.37+/-1.06. Newer imaging -SWI able to detects lesion better (diagnosis of DAI) as compared to other older sequences like FLAIR,DWI,T2*GRE. But no statistically significant found between total number of lesion/locations to the outcome and also newer imaging do not change the grade of DAI patients. Although advanced imaging in head injury, SWI helps in diagnosing the diffuse axonal injury more efficiently than other imaging sequences, but it is the grade of patients at admission that predicts the outcome best.

A disynaptic feedback network activated by experience promotes the integration of new granule cells.

PubMed

Alvarez, Diego D; Giacomini, Damiana; Yang, Sung Min; Trinchero, Mariela F; Temprana, Silvio G; Büttner, Karina A; Beltramone, Natalia; Schinder, Alejandro F

2016-10-28

Experience shapes the development and connectivity of adult-born granule cells (GCs) through mechanisms that are poorly understood. We examined the remodeling of dentate gyrus microcircuits in mice in an enriched environment (EE). Short exposure to EE during early development of new GCs accelerated their functional integration. This effect was mimicked by in vivo chemogenetic activation of a limited population of mature GCs. Slice recordings showed that mature GCs recruit parvalbumin γ-aminobutyric acid-releasing interneurons (PV-INs) that feed back onto developing GCs. Accordingly, chemogenetic stimulation of PV-INs or direct depolarization of developing GCs accelerated GC integration, whereas inactivation of PV-INs prevented the effects of EE. Our results reveal a mechanism for dynamic remodeling in which experience activates dentate networks that "prime" young GCs through a disynaptic feedback loop mediated by PV-INs. Copyright © 2016, American Association for the Advancement of Science.

Evolutionary history of the HAP2/GCS1 gene and sexual reproduction in metazoans.

PubMed

Steele, Robert E; Dana, Catherine E

2009-11-03

The HAP2/GCS1 gene first appeared in the common ancestor of plants, animals, and protists, and is required in the male gamete for fusion to the female gamete in the unicellular organisms Chlamydomonas and Plasmodium. We have identified a HAP2/GCS1 gene in the genome sequence of the sponge Amphimedon queenslandica. This finding provides a continuous evolutionary history of HAP2/GCS1 from unicellular organisms into the metazoan lineage. Divergent versions of the HAP2/GCS1 gene are also present in the genomes of some but not all arthropods. By examining the expression of the HAP2/GCS1 gene in the cnidarian Hydra, we have found the first evidence supporting the hypothesis that HAP2/GCS1 was used for male gamete fusion in the ancestor of extant metazoans and that it retains that function in modern cnidarians.

MOCCA-SURVEY Database I: Galactic Globular Clusters Harbouring a Black Hole Subsystem

NASA Astrophysics Data System (ADS)

Askar, Abbas; Sedda, Manuel Arca; Giersz, Mirek

2018-05-01

There have been increasing theoretical speculations and observational indications that certain globular clusters (GCs) could contain a sizeable population of stellar mass black holes (BHs). In this paper, we shortlist at least 29 Galactic GCs that could be hosting a subsystem of BHs (BHS). In a companion paper, we analysed results from a wide array of GC models (simulated with the MOCCA code for cluster simulations) that retained few tens to several hundreds of BHs at 12 Gyr and showed that the properties of the BHS in those GCs correlate with the GC's observable properties. Building on those results, we use available observational properties of 140 Galactic GCs to identify 29 GCs that could potentially be harbouring up to a few hundreds of BHs. Utilizing observational properties and theoretical scaling relations, we estimate the density, size and mass of the BHS in these GCs. We also calculate the total number of BHs and the fraction of BHs contained in a binary system for our shortlisted Galactic GCs. Additionally, we mention other Galactic GCs that could also contain significant number of single BHs or BHs in binary systems.

THE EFFECT OF SECOND-GENERATION POPULATIONS ON THE INTEGRATED COLORS OF METAL-RICH GLOBULAR CLUSTERS IN EARLY-TYPE GALAXIES

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

Chung, Chul; Lee, Sang-Yoon; Yoon, Suk-Jin

2013-05-20

The mean color of globular clusters (GCs) in early-type galaxies is in general bluer than the integrated color of halo field stars in host galaxies. Metal-rich GCs often appear more associated with field stars than metal-poor GCs, yet show bluer colors than their host galaxy light. Motivated by the discovery of multiple stellar populations in Milky Way GCs, we present a new scenario in which the presence of second-generation (SG) stars in GCs is responsible for the color discrepancy between metal-rich GCs and field stars. The model assumes that the SG populations have an enhanced helium abundance as evidenced bymore » observations, and it gives a good explanation of the bluer optical colors of metal-rich GCs than field stars as well as strong Balmer lines and blue UV colors of metal-rich GCs. Ours may be complementary to the recent scenario suggesting the difference in stellar mass functions (MFs) as an origin for the GC-to-star color offset. A quantitative comparison is given between the SG and MF models.« less

Steroid profiling reveals widespread local regulation of glucocorticoid levels during mouse development.

PubMed

Taves, Matthew D; Plumb, Adam W; Sandkam, Benjamin A; Ma, Chunqi; Van Der Gugten, Jessica Grace; Holmes, Daniel T; Close, David A; Abraham, Ninan; Soma, Kiran K

2015-02-01

Glucocorticoids (GCs) are produced by the adrenal glands and circulate in the blood to coordinate organismal physiology. In addition, different tissues may independently regulate their local GC levels via local GC synthesis. Here, we find that in the mouse, endogenous GCs show tissue-specific developmental patterns, rather than mirroring GCs in the blood. Using solid-phase extraction, HPLC, and specific immunoassays, we quantified endogenous steroids and found that in tissues of female and male mice, (1) local GC levels can be much higher than systemic GC levels, (2) local GCs follow age-related patterns different from those of systemic GCs, and (3) local GCs have identities different from those of systemic GCs. For example, whereas corticosterone is the predominant circulating adrenal GC in mice, high concentrations of cortisol were measured in neonatal thymus, bone marrow, and heart. The presence of cortisol was confirmed with liquid chromatography-tandem mass spectrometry. In addition, gene expression of steroidogenic enzymes was detected across multiple tissues, consistent with local GC production. Our results demonstrate that local GCs can differ from GCs in circulating blood. This finding suggests that steroids are widely used as local (paracrine or autocrine) signals, in addition to their classic role as systemic (endocrine) signals. Local GC regulation may even be the norm, rather than the exception, especially during development.

Prognostic value of FOUR and GCS scores in determining mortality in patients with traumatic brain injury.

PubMed

Saika, Amrit; Bansal, Sonia; Philip, Mariamma; Devi, Bhagavatula Indira; Shukla, Dhaval P

2015-09-01

The Glasgow Coma Scale (GCS) is considered the gold standard for assessment of unconsciousness in patients with traumatic brain injury (TBI) against which other scales are compared. To overcome the disadvantages of GCS, the Full Outline Of Unresponsiveness (FOUR) score was proposed. We aimed to compare the predictability of FOUR score and GCS for early mortality, after moderate and severe TBI. This is a prospective observational study of patients with moderate and severe TBI. Both FOUR and GCS scores were determined at admission. The primary outcome was mortality at the end of 2 weeks of injury. A total of 138 (117 males) patients were included in the study. Out of these, 17 (12.3 %) patients died within 2 weeks of injury. The mean GCS and FOUR scores were 9.5 (range, 3-13) and 11 (0-16), respectively. The total GCS and FOUR scores were significantly lower in patients who did not survive. At a cut-off score of 7 for FOUR score, the AUC was 0.97, with sensitivity of 97.5 and specificity of 88.2 % (p < 0.0001). For GCS score, AUC was 0.95, with sensitivity of 98.3 % and specificity of 82.4 % with cut-off score of 6 (p < 0.0001). The correlation coefficient was 0.753 (p < 0.001) between the GCS and FOUR scores. The predictive value of the FOUR score on admission of patients with TBI is no better than the GCS score.

Glasgow Coma Scale score, mortality, and functional outcome in head-injured patients.

PubMed

Udekwu, Pascal; Kromhout-Schiro, Sharon; Vaslef, Steven; Baker, Christopher; Oller, Dale

2004-05-01

Preresuscitation Glasgow Coma Scale (P-GCS) score is frequently obtained in injured patients and incorporated into mortality prediction. Data on functional outcome in head injury is sparse. A large group of patients with head injuries was analyzed to assess relationships between P-GCS score, mortality, and functional outcome as measured by the Functional Independence Measure (FIM). Records for patients with International Classification of Diseases, Ninth Revision diagnosis codes indicating head injury in a statewide trauma registry between 1994 and 2002 were selected. P-GCS score, mortality, and FIM score at hospital discharge were integrated and analyzed. Of 138,750 patients, 22,924 patients were used for the mortality study and 7,150 patients for the FIM study. A good correlation exists between P-GCS score and FIM, as determined by rank correlation coefficients, whereas mortality falls steeply between a P-GCS score of 3 and a P-GCS score of 7 followed by a shallow fall. Although P-GCS score is related to mortality in head-injured patients, its relationship is nonlinear, which casts doubt on its use as a continuous measure or an equivalent set of categorical measures incorporated into outcome prediction models. The average FIM scores indicate substantial likelihood of good outcomes in survivors with low P-GCS scores, further complicating the use of the P-GCS score in the prediction of poor outcome at the time of initial patient evaluation. Although the P-GCS score is related to functional outcome as measured by the FIM score and mortality in head injury, current mortality prediction models may need to be modified to account for the nonlinear relationship between P-GCS score and mortality. The P-GCS score is not a good clinical tool for outcome prediction in individual head-injured patients, given the variability in mortality rates and functional outcomes at all scores.

Inclusion of Highest Glasgow Coma Scale Motor Component Score in Mortality Risk Adjustment for Benchmarking of Trauma Center Performance.

PubMed

Gomez, David; Byrne, James P; Alali, Aziz S; Xiong, Wei; Hoeft, Chris; Neal, Melanie; Subacius, Harris; Nathens, Avery B

2017-12-01

The Glasgow Coma Scale (GCS) is the most widely used measure of traumatic brain injury (TBI) severity. Currently, the arrival GCS motor component (mGCS) score is used in risk-adjustment models for external benchmarking of mortality. However, there is evidence that the highest mGCS score in the first 24 hours after injury might be a better predictor of death. Our objective was to evaluate the impact of including the highest mGCS score on the performance of risk-adjustment models and subsequent external benchmarking results. Data were derived from the Trauma Quality Improvement Program analytic dataset (January 2014 through March 2015) and were limited to the severe TBI cohort (16 years or older, isolated head injury, GCS ≤8). Risk-adjustment models were created that varied in the mGCS covariates only (initial score, highest score, or both initial and highest mGCS scores). Model performance and fit, as well as external benchmarking results, were compared. There were 6,553 patients with severe TBI across 231 trauma centers included. Initial and highest mGCS scores were different in 47% of patients (n = 3,097). Model performance and fit improved when both initial and highest mGCS scores were included, as evidenced by improved C-statistic, Akaike Information Criterion, and adjusted R-squared values. Three-quarters of centers changed their adjusted odds ratio decile, 2.6% of centers changed outlier status, and 45% of centers exhibited a ≥0.5-SD change in the odds ratio of death after including highest mGCS score in the model. This study supports the concept that additional clinical information has the potential to not only improve the performance of current risk-adjustment models, but can also have a meaningful impact on external benchmarking strategies. Highest mGCS score is a good potential candidate for inclusion in additional models. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Hilar granule cells of the mouse dentate gyrus: effects of age, septotemporal location, strain, and selective deletion of the proapoptotic gene BAX.

PubMed

Bermudez-Hernandez, Keria; Lu, Yi-Ling; Moretto, Jillian; Jain, Swati; LaFrancois, John J; Duffy, Aine M; Scharfman, Helen E

2017-09-01

The dentate gyrus (DG) principal cells are glutamatergic granule cells (GCs), and they are located in a compact cell layer. However, GCs are also present in the adjacent hilar region, but have been described in only a few studies. Therefore, we used the transcription factor prospero homeobox 1 (Prox1) to quantify GCs at postnatal day (PND) 16, 30, and 60 in a common mouse strain, C57BL/6J mice. At PND16, there was a large population of Prox1-immunoreactive (ir) hilar cells, with more in the septal than temporal hippocampus. At PND30 and 60, the size of the hilar Prox1-ir cell population was reduced. Similar numbers of hilar Prox1-expressing cells were observed in PND30 and 60 Swiss Webster mice. Prox1 is usually considered to be a marker of postmitotic GCs. However, many Prox1-ir hilar cells, especially at PND16, were not double-labeled with NeuN, a marker typically found in mature neurons. Most hilar Prox1-positive cells at PND16 co-expressed doublecortin (DCX) and calretinin, markers of immature GCs. Double-labeling with a marker of actively dividing cells, Ki67, was not detected. These results suggest that, surprisingly, a large population of cells in the hilus at PND16 are immature GCs (Type 2b and Type 3 cells). We also asked whether hilar Prox1-ir cell numbers are modifiable. To examine this issue, we conditionally deleted the proapoptotic gene BAX in Nestin-expressing cells at a time when there are numerous immature GCs in the hilus, PND2-8. When these mice were examined at PND60, the numbers of Prox1-ir hilar cells were significantly increased compared to control mice. However, deletion of BAX did not appear to change the proportion that co-expressed NeuN, suggesting that the size of the hilar Prox1-expressing population is modifiable. However, deleting BAX, a major developmental disruption, does not appear to change the proportion that ultimately becomes neurons.

The effects of the environmental antiandrogen vinclozolin on the induction of granulosa cell apoptosis during follicular atresia in pigs.

PubMed

Knet, Malgorzata; Tabarowski, Zbigniew; Slomczynska, Maria; Duda, Malgorzata

2014-06-01

The aim of this study was to investigate whether the androgens testosterone and dihydrotestosterone (DHT) and the antiandrogenic fungicide vinclozolin (Vnz) exert proapoptotic effects on porcine granulosa cells (GCs), and to examine the roles of these compounds in follicular atresia. Granulosa cells isolated from pig follicles were cultured for 24 hours, and then exposed to 0.1 μM testosterone, 0.1 μM DHT, 14 μM Vnz, or the equivalent concentrations of testosterone and Vnz or DHT and Vnz for a further 24 hours. Apoptosis and necrosis of the GCs were determined via Hoechst staining and flow cytometry analyses of annexin V-stained cells. Whole porcine follicles were also exposed to the same compounds and combinations of compounds for 24 hours. The sections were stained with hematoxylin and eosin for morphologic assessments, and a Terminal deoxynucleotidyl Transferase Biotyn-dUTP Nick-End Labeling (TUNEL) assay was performed to determine the number of apoptotic cells. The progesterone and estradiol concentrations secreted into the culture media by isolated GCs and follicles were also measured. Exposure to the androgens resulted in an increased number of apoptotic GCs both in vitro and in the organotypic model. Vinclozolin exposure increased and decreased the number of necrotic and apoptotic GCs, respectively. Furthermore, compared with control follicles, those exposed to testosterone, DHT, or Vnz displayed enhanced atresia, and coadministration of Vnz attenuated the promotive effect of these androgens on atresia. Estradiol secretion was stimulated by the combination of testosterone and Vnz, whereas exposure to Vnz alone reduced it. Progesterone production declined after the combined addition of androgens and the antiandrogen. In summary, Vnz caused massive necrosis of GCs in vitro and induced apoptosis of GCs in whole follicles. The androgens testosterone and DHT enhanced these effects. The results presented here suggest that selective destruction of porcine follicles is a serious consequence of exposure to Vnz, and may lead to premature ovarian failure in affected animals. Copyright © 2014 Elsevier Inc. All rights reserved.

The Arabidopsis arc5 and arc6 mutations differentially affect plastid morphology in pavement and guard cells in the leaf epidermis.

PubMed

Fujiwara, Makoto T; Yasuzawa, Mana; Kojo, Kei H; Niwa, Yasuo; Abe, Tomoko; Yoshida, Shigeo; Nakano, Takeshi; Itoh, Ryuuichi D

2018-01-01

Chloroplasts, or photosynthetic plastids, multiply by binary fission, forming a homogeneous population in plant cells. In Arabidopsis thaliana, the division apparatus (or division ring) of mesophyll chloroplasts includes an inner envelope transmembrane protein ARC6, a cytoplasmic dynamin-related protein ARC5 (DRP5B), and members of the FtsZ1 and FtsZ2 families of proteins, which co-assemble in the stromal mid-plastid division ring (FtsZ ring). FtsZ ring placement is controlled by several proteins, including a stromal factor MinE (AtMinE1). During leaf mesophyll development, ARC6 and AtMinE1 are necessary for FtsZ ring formation and thus plastid division initiation, while ARC5 is essential for a later stage of plastid division. Here, we examined plastid morphology in leaf epidermal pavement cells (PCs) and stomatal guard cells (GCs) in the arc5 and arc6 mutants using stroma-targeted fluorescent proteins. The arc5 PC plastids were generally a bit larger than those of the wild type, but most had normal shapes and were division-competent, unlike mutant mesophyll chloroplasts. The arc6 PC plastids were heterogeneous in size and shape, including the formation of giant and mini-plastids, plastids with highly developed stromules, and grape-like plastid clusters, which varied on a cell-by-cell basis. Moreover, unique plastid phenotypes for stomatal GCs were observed in both mutants. The arc5 GCs rarely lacked chlorophyll-bearing plastids (chloroplasts), while they accumulated minute chlorophyll-less plastids, whereas most GCs developed wild type-like chloroplasts. The arc6 GCs produced large chloroplasts and/or chlorophyll-less plastids, as previously observed, but unexpectedly, their chloroplasts/plastids exhibited marked morphological variations. We quantitatively analyzed plastid morphology and partitioning in paired GCs from wild-type, arc5, arc6, and atminE1 plants. Collectively, our results support the notion that ARC5 is dispensable in the process of equal division of epidermal plastids, and indicate that dysfunctions in ARC5 and ARC6 differentially affect plastid replication among mesophyll cells, PCs, and GCs within a single leaf.

THE AGES, METALLICITIES, AND ALPHA ELEMENT ENHANCEMENTS OF GLOBULAR CLUSTERS IN THE ELLIPTICAL NGC 5128: A HOMOGENEOUS SPECTROSCOPIC STUDY WITH GEMINI/GEMINI MULTI-OBJECT SPECTROGRAPH

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

Woodley, Kristin A.; Harris, William E.; Puzia, Thomas H.

2010-01-10

We present new integrated light spectroscopy of globular clusters (GCs) in NGC 5128, a nearby giant elliptical galaxy less than 4 Mpc away, in order to measure radial velocities and derive ages, metallicities, and alpha-element abundance ratios. Using the Gemini South 8 meter telescope with the instrument Gemini Multi-Object Spectrograph, we obtained spectroscopy in the range of approx3400-5700 A for 72 GCs with a signal-to-noise ratio greater than 30 A{sup -1}; and we have also discovered 35 new GCs within NGC 5128 from our radial velocity measurements. We measured and compared the Lick indices from Hdelta{sub A} through Fe5406 withmore » the single stellar population models of Thomas et al. in order to derive age, metallicity, and [alpha/Fe] values. We also measure Lick indices for 41 Milky Way GCs from Puzia et al. and Schiavon et al. with the same methodology for direct comparison. Our results show that 68% of the NGC 5128 GCs have old ages (>8 Gyr), 14% have intermediate ages (5-8 Gyr), and 18% have young ages (<5 Gyr). However, when we look at the metallicity of the GCs as a function of age, we find 92% of metal-poor GCs and 56% of metal-rich GCs in NGC 5128 have ages >8 Gyr, indicating that the majority of both metallicity subpopulations of GCs formed earlier, with a significant population of young and metal-rich GCs forming later. Our metallicity distribution function generated directly from spectroscopic Lick indices is clearly bimodal, as is the color distribution of the same set of GCs. Thus, the metallicity bimodality is real and not an artifact of the color to metallicity conversion. However, the metallicity distribution function obtained from comparison with the single stellar population models is consistent with a unimodal, bimodal, or multimodal shape. The [alpha/Fe] values are supersolar with a mean value of 0.14 +- 0.04, indicating a fast formation timescale. However, the GCs in NGC 5128 are not as [alpha/Fe] enhanced as the Milky Way GCs also examined in this study. Our measured indices also indicate that the GCs in NGC 5128 may have a slight overabundance in nitrogen and a wider range of calcium strength compared to the Milky Way GCs. Our results support a rapid, early formation of the GC system in NGC 5128, with subsequent major accretion and/or GC and star-forming events in more recent times.« less

VEGAS-SSS. II. Comparing the globular cluster systems in NGC 3115 and NGC 1399 using VEGAS and FDS survey data. The quest for a common genetic heritage of globular cluster systems

NASA Astrophysics Data System (ADS)

Cantiello, Michele; D'Abrusco, Raffaele; Spavone, Marilena; Paolillo, Maurizio; Capaccioli, Massimo; Limatola, Luca; Grado, Aniello; Iodice, Enrica; Raimondo, Gabriella; Napolitano, Nicola; Blakeslee, John P.; Brocato, Enzo; Forbes, Duncan A.; Hilker, Michael; Mieske, Steffen; Peletier, Reynier; van de Ven, Glenn; Schipani, Pietro

2018-04-01

We analyze the globular cluster (GC) systems in two very different galaxies, NGC 3115 and NGC 1399. With the papers of this series, we aim at highlighting common and different properties in the GC systems in galaxies covering a wide range of parameter space. We compare the GCs in NGC 3115 and NGC 1399 as derived from the analysis of one square degree u-, g-, and i-band images taken with the VST telescope as part of the VST early-type galaxy survey (VEGAS) and Fornax deep survey (FDS). We selected GC candidates using as reference the morpho-photometric and color properties of confirmed GCs. The surface density maps of GCs in NGC 3115 reveal a morphology similar to the light profile of field stars; the same is true when blue and red GCs are taken separately. The GC maps for NGC 1399 are richer in structure and confirm the existence of an intra-cluster GC component. We confirm the presence of a spatial offset in the NGC 1399 GC centroid and find that the centroid of the GCs for NGC 3115 coincides well with the galaxy center. Both GC systems show unambiguous color bimodality in (g - i) and (u - i); the color-color relations of the two GC systems are slightly different with NGC 3115 appearing more linear than NGC 1399. The azimuthal average of the radial density profiles in both galaxies reveals a larger spatial extent for the total GCs population with respect to the galaxy surface brightness profile. For both galaxies, the red GCs have radial density profiles compatible with the galaxy light profile, while the radial profiles for blue GCs are shallower. As for the specific frequency of GCs, SN, we find it is a factor of two higher in NGC 1399 than for NGC 3115; this is mainly the result of extra blue GCs. By inspecting the radial behavior of the specific frequency, SN(

Evidence of differential tidal effects in the old globular cluster population of the Large Magellanic Cloud

NASA Astrophysics Data System (ADS)

Piatti, A. E.; Mackey, A. D.

2018-04-01

We present for the first time extended stellar density and/or surface brightness radial profiles for almost all the known Large Magellanic Cloud (LMC) old globular clusters (GCs). These were built from DECam images and reach out to ˜ 4 times the GCs' tidal radii. The background subtracted radial profiles reveal that the GCs located closer than ˜ 5 kpc from the LMC centre contain an excess of stars in their outermost regions with respect to the stellar density expected from a King profile. Such a residual amount of stars - not seen in GCs located farther than ˜ 5 kpc from the LMC centre-, as well as the GCs' dimensions, show a clear dependence with the GCs' positions in the galaxy, in the sense that, the farther the GC from the centre of the LMC, the larger both the excess of stars in its outskirts and size. Although the masses of GCs located inside and outside ˜ 5 kpc are commensurate, the outermost regions of GCs located closer than ˜ 5 kpc from the LMC centre appear to have dynamically evolved more quickly. These outcomes can be fully interpreted in the light of the known GC radial velocity disc-like kinematics, from which GCs have been somehow mostly experiencing the influence of the LMC gravitational field at their respective mean distances from the LMC centre.

Development of an Intelligent Monitoring System for Geological Carbon Sequestration (GCS) Systems

NASA Astrophysics Data System (ADS)

Sun, A. Y.; Jeong, H.; Xu, W.; Hovorka, S. D.; Zhu, T.; Templeton, T.; Arctur, D. K.

2016-12-01

To provide stakeholders timely evidence that GCS repositories are operating safely and efficiently requires integrated monitoring to assess the performance of the storage reservoir as the CO2 plume moves within it. As a result, GCS projects can be data intensive, as a result of proliferation of digital instrumentation and smart-sensing technologies. GCS projects are also resource intensive, often requiring multidisciplinary teams performing different monitoring, verification, and accounting (MVA) tasks throughout the lifecycle of a project to ensure secure containment of injected CO2. How to correlate anomaly detected by a certain sensor to events observed by other devices to verify leakage incidents? How to optimally allocate resources for task-oriented monitoring if reservoir integrity is in question? These are issues that warrant further investigation before real integration can take place. In this work, we are building a web-based, data integration, assimilation, and learning framework for geologic carbon sequestration projects (DIAL-GCS). DIAL-GCS will be an intelligent monitoring system (IMS) for automating GCS closed-loop management by leveraging recent developments in high-throughput database, complex event processing, data assimilation, and machine learning technologies. Results will be demonstrated using realistic data and model derived from a GCS site.

SIRT1 induces resistance to apoptosis in human granulosa cells by activating the ERK pathway and inhibiting NF-κB signaling with anti-inflammatory functions.

PubMed

Han, Ying; Luo, Haining; Wang, Hui; Cai, Jun; Zhang, Yunshan

2017-10-01

SIRT1, a member of the sirtuin family, has recently emerged as a vital molecule in controlling ovarian function. The aims of the present study were to investigate SIRT1 expression and analyze SIRT1-mediated apoptosis in human granulosa cells (GCs). Human ovarian tissues were subjected to immunohistochemistry for localization of SIRT1 expression. SIRT1 knockdown in a human ovarian GC tumor line (COV434) was achieved by small interfering RNA, and the relationship between apoptosis and SIRT1 was assessed by quantitative reverse transcription polymerase chain reaction and western blotting. We further detected SIRT1 expression in human luteinized GCs. Associations among SIRT1 knockdown, SIRT1 stimulation (resveratrol) and expression of ERK1/2 and apoptotic regulatory proteins were analyzed in cell lines and luteinized GCs. Resveratrol downregulated the levels of nuclear factor (NF)-κB/p65, but this inhibitory effect was attenuated by suppressing SIRT1 activity. The NF-κB/p65 inhibitor pyrrolidine dithiocarbamate achieved similar anti-apoptosis effects. These results suggest that SIRT1 might play an anti-apoptotic role in apoptosis processes in GCs, possibly by sensing and regulating the ERK1/2 pathway, which has important clinical implications. Thus, our study provides a mechanistic link, whereby activation of SIRT1 function might help to sustain human reproduction by maintaining GCs as well as oocytes, offering a novel approach for developing a new class of therapeutic anti-inflammatory agents.

Predictive Utility of the Total Glasgow Coma Scale Versus the Motor Component of the Glasgow Coma Scale for Identification of Patients With Serious Traumatic Injuries.

PubMed

Chou, Roger; Totten, Annette M; Carney, Nancy; Dandy, Spencer; Fu, Rongwei; Grusing, Sara; Pappas, Miranda; Wasson, Ngoc; Newgard, Craig D

2017-08-01

The motor component of the Glasgow Coma Scale (mGCS) has been proposed as an easier-to-use alternative to the total GCS (tGCS) for field assessment of trauma patients by emergency medical services. We perform a systematic review and meta-analysis to compare the predictive utility of the tGCS versus the mGCS or Simplified Motor Scale in field triage of trauma for identifying patients with adverse outcomes (inhospital mortality or severe brain injury) or who underwent procedures (neurosurgical intervention or emergency intubation) indicating need for high-level trauma care. Ovid MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Health and Psychosocial Instruments, and the Cochrane databases were searched through June 2016 for English-language cohort studies. We included studies that compared the area under the receiver operating characteristic curve (AUROC) of the tGCS versus the mGCS or Simplified Motor Scale assessed in the field or shortly after arrival in the emergency department for predicting the outcomes described above. Meta-analyses were performed with a random-effects model, and subgroup and sensitivity analyses were conducted. We included 18 head-to-head studies of predictive utility (n=1,703,388). For inhospital mortality, the tGCS was associated with slightly greater discrimination than the mGCS (pooled mean difference in [AUROC] 0.015; 95% confidence interval [CI] 0.009 to 0.022; I 2 =85%; 12 studies) or the Simplified Motor Scale (pooled mean difference in AUROC 0.030; 95% CI 0.024 to 0.036; I 2 =0%; 5 studies). The tGCS was also associated with greater discrimination than the mGCS or Simplified Motor Scale for nonmortality outcomes (differences in AUROC from 0.03 to 0.05). Findings were robust in subgroup and sensitivity analyses. The tGCS is associated with slightly greater discrimination than the mGCS or Simplified Motor Scale for identifying severe trauma. The small differences in discrimination are likely to be clinically unimportant and could be offset by factors such as convenience and ease of use. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells

PubMed Central

Hasni Ebou, Moina; Singh-Estivalet, Amrit; Launay, Jean-Marie; Callebert, Jacques; Tronche, François; Ferré, Pascal; Gautier, Jean-François; Guillemain, Ghislaine; Bréant, Bernadette

2016-01-01

Diabetes is a major complication of chronic Glucocorticoids (GCs) treatment. GCs induce insulin resistance and also inhibit insulin secretion from pancreatic beta cells. Yet, a full understanding of this negative regulation remains to be deciphered. In the present study, we investigated whether GCs could inhibit serotonin synthesis in beta cell since this neurotransmitter has been shown to be involved in the regulation of insulin secretion. To this aim, serotonin synthesis was evaluated in vitro after treatment with GCs of either islets from CD1 mice or MIN6 cells, a beta-cell line. We also explored the effect of GCs on the stimulation of serotonin synthesis by several hormones such as prolactin and GLP 1. We finally studied this regulation in islet in two in vivo models: mice treated with GCs and with liraglutide, a GLP1 analog, and mice deleted for the glucocorticoid receptor in the pancreas. We showed in isolated islets and MIN6 cells that GCs decreased expression and activity of the two key enzymes of serotonin synthesis, Tryptophan Hydroxylase 1 (Tph1) and 2 (Tph2), leading to reduced serotonin contents. GCs also blocked the induction of serotonin synthesis by prolactin or by a previously unknown serotonin activator, the GLP-1 analog exendin-4. In vivo, activation of the Glucagon-like-Peptide-1 receptor with liraglutide during 4 weeks increased islet serotonin contents and GCs treatment prevented this increase. Finally, islets from mice deleted for the GR in the pancreas displayed an increased expression of Tph1 and Tph2 and a strong increased serotonin content per islet. In conclusion, our results demonstrate an original inhibition of serotonin synthesis by GCs, both in basal condition and after stimulation by prolactin or activators of the GLP-1 receptor. This regulation may contribute to the deleterious effects of GCs on beta cells. PMID:26901633

The Next Generation Virgo Cluster Survey. VI. The Kinematics of Ultra-compact Dwarfs and Globular Clusters in M87

NASA Astrophysics Data System (ADS)

Zhang, Hong-Xin; Peng, Eric W.; Côté, Patrick; Liu, Chengze; Ferrarese, Laura; Cuillandre, Jean-Charles; Caldwell, Nelson; Gwyn, Stephen D. J.; Jordán, Andrés; Lançon, Ariane; Li, Biao; Muñoz, Roberto P.; Puzia, Thomas H.; Bekki, Kenji; Blakeslee, John P.; Boselli, Alessandro; Drinkwater, Michael J.; Duc, Pierre-Alain; Durrell, Patrick; Emsellem, Eric; Firth, Peter; Sánchez-Janssen, Rubén

2015-03-01

The origin of ultra-compact dwarfs (UCDs; rh >~ 10 pc)—objects larger and more massive than typical globular clusters (GCs), but more compact than typical dwarf galaxies—has been hotly debated in the 15 years since their discovery. Even whether UCDs should be considered galactic in origin, or simply the most extreme star clusters, is not yet settled. We present the dynamical properties of 97 spectroscopically confirmed UCDs and 911 GCs associated with the central cD galaxy of the Virgo cluster, M87. Our UCDs, of which 89% have M sstarf gsim 2× 106 M ⊙ and 92% are as blue as the classic blue GCs, nearly triple the confirmed sample of Virgo UCDs, providing by far the best opportunity for studying global dynamics of a UCD system. We found that (1) UCDs have a surface number density profile that is shallower than that of blue GCs in the inner ~70 kpc and as steep as that of red GCs at larger radii; (2) UCDs exhibit a significantly stronger rotation than GCs, and blue GCs seem to have a velocity field that is more consistent with that of the surrounding dwarf ellipticals than with that of UCDs; (3) UCDs have an orbital anisotropy profile that is tangentially biased at radii lsim40 kpc and radially biased farther out, whereas blue GCs become more tangentially biased at larger radii beyond ~40 kpc (4) GCs with M sstarf gsim 2 × 106 M ⊙ have rotational properties indistinguishable from the less massive ones, suggesting that it is the size, instead of mass, that differentiates UCDs from GCs as kinematically distinct populations. We conclude that most UCDs in M87 are not consistent with being merely the most luminous and extended examples of otherwise normal GCs. The radially biased orbital structure of UCDs at large radii is in general agreement with the "tidally threshed dwarf galaxy" scenario.

Glasgow Coma Scale and Outcomes after Structural Traumatic Head Injury in Early Childhood

PubMed Central

Heather, Natasha L.; Derraik, José G. B.; Beca, John; Hofman, Paul L.; Dansey, Rangi; Hamill, James; Cutfield, Wayne S.

2013-01-01

Objective To assess the association of the Glasgow Coma Scale (GCS) with radiological evidence of head injury (the Abbreviated Injury Scale for the head region, AIS-HR) in young children hospitalized with traumatic head injury (THI), and the predictive value of GCS and AIS-HR scores for long-term impairment. Methods Our study involved a 10-year retrospective review of a database encompassing all patients admitted to Starship Children’s Hospital (Auckland, New Zealand, 2000–2010) with THI. Results We studied 619 children aged <5 years at the time of THI, with long-term outcome data available for 161 subjects. Both GCS and AIS-HR scores were predictive of length of intensive care unit and hospital stay (all p<0.001). GCS was correlated with AIS-HR (ρ=-0.46; p<0.001), although mild GCS scores (13–15) commonly under-estimated the severity of radiological injury: 42% of children with mild GCS scores had serious–critical THI (AIS-HR 3–5). Increasingly severe GCS or AIS-HR scores were both associated with a greater likelihood of long-term impairment (neurological disability, residual problems, and educational support). However, long-term impairment was also relatively common in children with mild GCS scores paired with structural THI more severe than a simple linear skull fracture. Conclusion Severe GCS scores will identify most cases of severe radiological injury in early childhood, and are good predictors of poor long-term outcome. However, young children admitted to hospital with structural THI and mild GCS scores have an appreciable risk of long-term disability, and also warrant long-term follow-up. PMID:24312648

Usefulness of the abbreviated injury score and the injury severity score in comparison to the Glasgow Coma Scale in predicting outcome after traumatic brain injury.

PubMed

Foreman, Brandon P; Caesar, R Ruth; Parks, Jennifer; Madden, Christopher; Gentilello, Larry M; Shafi, Shahid; Carlile, Mary C; Harper, Caryn R; Diaz-Arrastia, Ramon R

2007-04-01

Assessment of injury severity is important in the management of patients with brain trauma. We aimed to analyze the usefulness of the head abbreviated injury score (AIS), the injury severity score (ISS), and the Glasgow Coma Scale (GCS) as measures of injury severity and predictors of outcome after traumatic brain injury (TBI). Data were prospectively collected from 410 patients with TBI. AIS, ISS, and GCS were recorded at admission. Subjects' outcomes after TBI were measured using the Glasgow Outcome Scale (GOS-E) at 12 months postinjury. Uni- and multivariate analyses were performed. Outcome information was obtained from 270 patients (66%). ISS was the best predictor of GOS-E (rs = -0.341, p < 0.001), followed by GCS score (rs = 0.227, p < 0.001), and head AIS (rs = -0.222, p < 0.001). When considered in combination, GCS score and ISS modestly improved the correlation with GOS-E (R = 0.335, p < 0.001). The combination of GCS score and head AIS had a similar effect (R = 0.275, p < 0.001). Correlations were stronger from patients 8). GCS score, AIS, and ISS are weakly correlated with 12-month outcome. However, anatomic measures modestly outperform GCS as predictors of GOS-E. The combination of GCS and AIS/ISS correlate with outcome better than do any of the three measures alone. Results support the addition of anatomic measures such as AIS and ISS in clinical studies of TBI. Additionally, most of the variance in outcome is not accounted for by currently available measures of injury severity.

The effect of metformin treatment in vivo on acute and long-term energy metabolism and progesterone production in vitro by granulosa cells from women with polycystic ovary syndrome

PubMed Central

Maruthini, D.; Harris, S.E.; Barth, J.H.; Balen, A.H.; Campbell, B.K.; Picton, H.M.

2014-01-01

STUDY QUESTION What are the consequences of polycystic ovary syndrome (PCOS) pathology and metformin-pretreatment in vivo in women with PCOS on the metabolism and steroid production of follicular phenotype- and long-term cultured-granulosa cells (GC)? SUMMARY ANSWER PCOS pathology significantly compromised glucose metabolism and the progesterone synthetic capacity of follicular- and long-term cultured-GCs and the metabolic impact of PCOS on GC function was alleviated by metformin-pretreatment in vivo. WHAT IS KNOWN ALREADY Granulosa cells from women with PCOS have been shown to have an impaired insulin-stimulated glucose uptake and lactate production in vitro. However, these results were obtained by placing GCs in unphysiological conditions in culture medium containing high glucose and insulin concentrations. Moreover, existing data on insulin-responsive steroid production in vitro by PCOS GCs vary. STUDY DESIGN, SIZE AND DURATION Case-control experimental research comparing glucose uptake, pyruvate and lactate production and progesterone production in vitro by GCs from three aetiological groups, all undergoing IVF; healthy control women (Control, n = 12), women with PCOS treated with metformin in vivo (Metformin, n = 8) and women with PCOS not exposed to metformin (PCOS, n = 8). The study was conducted over a period of 3 years between 2007 and 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS Rotterdam criteria were used for the diagnosis of PCOS; all subjects were matched for age, BMI and baseline FSH. Individual patient cultures were undertaken with cells incubated in a validated, physiological, serum-free culture medium containing doses of 0–6 mM glucose and 0–100 ng/ml insulin for 6 h and 144 h to quantify the impact of treatments on acute and long-term metabolism, respectively, and progesterone production. The metabolite content of spent media was measured using spectrophotometric plate reader assay. The progesterone content of spent media was measured by enzyme-linked immunosorbent assay. Viable GC number was quantified after 144 h of culture by the vital dye Neutral Red uptake assay. MAIN RESULTS AND THE ROLE OF CHANCE Granulosa cells from women with PCOS pathology revealed reduced pyruvate production and preferential lactate production in addition to their reduced glucose uptake during cultures (P < 0.05). Metformin pretreatment alleviated this metabolic lesion (P < 0.05) and enhanced cell proliferation in vitro (P < 0.05), but cells retained a significantly reduced capacity for progesterone synthesis compared with controls (P < 0.05). LIMITATIONS, REASONS FOR CAUTION Although significant treatment effects were detected in this small cohort, further studies are required to underpin the molecular mechanisms of the effect of metformin on GCs. WIDER IMPLICATIONS OF THE FINDINGS The individual patient culture strategy combined with multifactorial experimental design strengthens the biological interpretation of the data. Collectively, these results support the notion that there is an inherent impairment in progesterone biosynthetic capacity of the GCs from women with PCOS. The positive, acute metabolic effect and the negative long-term steroidogenic effect on GCs following metformin exposure in vivo may have important implications for follicular development and luteinized GC function when the drug is used in clinical practice. STUDY FUNDING/COMPETING INTEREST(S) No competing interests. This work was supported by the UK Medical Research Council Grant Reference number G0800250. PMID:25139174

The effect of metformin treatment in vivo on acute and long-term energy metabolism and progesterone production in vitro by granulosa cells from women with polycystic ovary syndrome.

PubMed

Maruthini, D; Harris, S E; Barth, J H; Balen, A H; Campbell, B K; Picton, H M

2014-10-10

What are the consequences of polycystic ovary syndrome (PCOS) pathology and metformin-pretreatment in vivo in women with PCOS on the metabolism and steroid production of follicular phenotype- and long-term cultured-granulosa cells (GC)? PCOS pathology significantly compromised glucose metabolism and the progesterone synthetic capacity of follicular- and long-term cultured-GCs and the metabolic impact of PCOS on GC function was alleviated by metformin-pretreatment in vivo. Granulosa cells from women with PCOS have been shown to have an impaired insulin-stimulated glucose uptake and lactate production in vitro. However, these results were obtained by placing GCs in unphysiological conditions in culture medium containing high glucose and insulin concentrations. Moreover, existing data on insulin-responsive steroid production in vitro by PCOS GCs vary. Case-control experimental research comparing glucose uptake, pyruvate and lactate production and progesterone production in vitro by GCs from three aetiological groups, all undergoing IVF; healthy control women (Control, n = 12), women with PCOS treated with metformin in vivo (Metformin, n = 8) and women with PCOS not exposed to metformin (PCOS, n = 8). The study was conducted over a period of 3 years between 2007 and 2010. Rotterdam criteria were used for the diagnosis of PCOS; all subjects were matched for age, BMI and baseline FSH. Individual patient cultures were undertaken with cells incubated in a validated, physiological, serum-free culture medium containing doses of 0-6 mM glucose and 0-100 ng/ml insulin for 6 h and 144 h to quantify the impact of treatments on acute and long-term metabolism, respectively, and progesterone production. The metabolite content of spent media was measured using spectrophotometric plate reader assay. The progesterone content of spent media was measured by enzyme-linked immunosorbent assay. Viable GC number was quantified after 144 h of culture by the vital dye Neutral Red uptake assay. Granulosa cells from women with PCOS pathology revealed reduced pyruvate production and preferential lactate production in addition to their reduced glucose uptake during cultures (P < 0.05). Metformin pretreatment alleviated this metabolic lesion (P < 0.05) and enhanced cell proliferation in vitro (P < 0.05), but cells retained a significantly reduced capacity for progesterone synthesis compared with controls (P < 0.05). Although significant treatment effects were detected in this small cohort, further studies are required to underpin the molecular mechanisms of the effect of metformin on GCs. The individual patient culture strategy combined with multifactorial experimental design strengthens the biological interpretation of the data. Collectively, these results support the notion that there is an inherent impairment in progesterone biosynthetic capacity of the GCs from women with PCOS. The positive, acute metabolic effect and the negative long-term steroidogenic effect on GCs following metformin exposure in vivo may have important implications for follicular development and luteinized GC function when the drug is used in clinical practice. No competing interests. This work was supported by the UK Medical Research Council Grant Reference number G0800250. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Unique processing during a period of high excitation/inhibition balance in adult-born neurons.

PubMed

Marín-Burgin, Antonia; Mongiat, Lucas A; Pardi, M Belén; Schinder, Alejandro F

2012-03-09

The adult dentate gyrus generates new granule cells (GCs) that develop over several weeks and integrate into the preexisting network. Although adult hippocampal neurogenesis has been implicated in learning and memory, the specific role of new GCs remains unclear. We examined whether immature adult-born neurons contribute to information encoding. By combining calcium imaging and electrophysiology in acute slices, we found that weak afferent activity recruits few mature GCs while activating a substantial proportion of the immature neurons. These different activation thresholds are dictated by an enhanced excitation/inhibition balance transiently expressed in immature GCs. Immature GCs exhibit low input specificity that switches with time toward a highly specific responsiveness. Therefore, activity patterns entering the dentate gyrus can undergo differential decoding by a heterogeneous population of GCs originated at different times.

Coherent and Semiclassical States of a Charged Particle in Electromagnetic Fields

NASA Astrophysics Data System (ADS)

Pereira, A. S.

2018-06-01

In the present article, we extend our study (Bagrov et al., Braz. J. Phys. 45, 369, 2015) of generalized coherent states (GCS) of a one-dimensional particle considering such important physical system as a three-dimensional charged particle in electric and magnetic fields. Constructing GCS in a many-dimensional case, we meet technical complications that make the consideration nontrivial and instructive. The GCS of the system under consideration are constructed. We study the properties of this GCS such as completeness relations, minimization of uncertainty relations, and so on. We point out which family of the obtained GCS of a charged particle in a magnetic field is related to the CS constructed first by Malkin and Man'ko. We obtain conditions under which some of the GCS can be considered as semiclassical states (SS).

Coherent and Semiclassical States of a Charged Particle in Electromagnetic Fields

NASA Astrophysics Data System (ADS)

Pereira, A. S.

2018-03-01

In the present article, we extend our study (Bagrov et al., Braz. J. Phys. 45, 369, 2015) of generalized coherent states (GCS) of a one-dimensional particle considering such important physical system as a three-dimensional charged particle in electric and magnetic fields. Constructing GCS in a many-dimensional case, we meet technical complications that make the consideration nontrivial and instructive. The GCS of the system under consideration are constructed. We study the properties of this GCS such as completeness relations, minimization of uncertainty relations, and so on. We point out which family of the obtained GCS of a charged particle in a magnetic field is related to the CS constructed first by Malkin and Man'ko. We obtain conditions under which some of the GCS can be considered as semiclassical states (SS).

Mortality prediction of head Abbreviated Injury Score and Glasgow Coma Scale: analysis of 7,764 head injuries.

PubMed

Demetriades, Demetrios; Kuncir, Eric; Murray, James; Velmahos, George C; Rhee, Peter; Chan, Linda

2004-08-01

We assessed the prognostic value and limitations of Glasgow Coma Scale (GCS) and head Abbreviated Injury Score (AIS) and correlated head AIS with GCS. We studied 7,764 patients with head injuries. Bivariate analysis was performed to examine the relationship of GCS, head AIS, age, gender, and mechanism of injury with mortality. Stepwise logistic regression analysis was used to identify the independent risk factors associated with mortality. The overall mortality in the group of head injury patients with no other major extracranial injuries and no hypotension on admission was 9.3%. Logistic regression analysis identified head AIS, GCS, age, and mechanism of injury as significant independent risk factors of death. The prognostic value of GCS and head AIS was significantly affected by the mechanism of injury and the age of the patient. Patients with similar GCS or head AIS but different mechanisms of injury or ages had significantly different outcomes. The adjusted odds ratio of death in penetrating trauma was 5.2 (3.9, 7.0), p < 0.0001, and in the age group > or = 55 years the adjusted odds ratio was 3.4 (2.6, 4.6), p < 0.0001. There was no correlation between head AIS and GCS (correlation coefficient -0.31). Mechanism of injury and age have a major effect in the predictive value of GCS and head AIS. There is no good correlation between GCS and head AIS.

Glucocorticoids promote Von Hippel Lindau degradation and Hif-1α stabilization

PubMed Central

Greenald, David; Wilson, Garrick K.; Peron, Margherita; Markham, Eleanor; Sinnakaruppan, Mathavan; Matthews, Laura C.; McKeating, Jane A.; Argenton, Francesco; van Eeden, Fredericus J. M.

2017-01-01

Glucocorticoid (GC) and hypoxic transcriptional responses play a central role in tissue homeostasis and regulate the cellular response to stress and inflammation, highlighting the potential for cross-talk between these two signaling pathways. We present results from an unbiased in vivo chemical screen in zebrafish that identifies GCs as activators of hypoxia-inducible factors (HIFs) in the liver. GCs activated consensus hypoxia response element (HRE) reporters in a glucocorticoid receptor (GR)-dependent manner. Importantly, GCs activated HIF transcriptional responses in a zebrafish mutant line harboring a point mutation in the GR DNA-binding domain, suggesting a nontranscriptional route for GR to activate HIF signaling. We noted that GCs increase the transcription of several key regulators of glucose metabolism that contain HREs, suggesting a role for GC/HIF cross-talk in regulating glucose homeostasis. Importantly, we show that GCs stabilize HIF protein in intact human liver tissue and isolated hepatocytes. We find that GCs limit the expression of Von Hippel Lindau protein (pVHL), a negative regulator of HIF, and that treatment with the c-src inhibitor PP2 rescued this effect, suggesting a role for GCs in promoting c-src–mediated proteosomal degradation of pVHL. Our data support a model for GCs to stabilize HIF through activation of c-src and subsequent destabilization of pVHL. PMID:28851829

Time-lapse imaging reveals highly dynamic structural maturation of postnatally born dentate granule cells in organotypic entorhino-hippocampal slice cultures

PubMed Central

Radic, Tijana; Jungenitz, Tassilo; Singer, Mathias; Beining, Marcel; Cuntz, Hermann; Vlachos, Andreas; Deller, Thomas; Schwarzacher, Stephan W.

2017-01-01

Neurogenesis of hippocampal granule cells (GCs) persists throughout mammalian life and is important for learning and memory. How newborn GCs differentiate and mature into an existing circuit during this time period is not yet fully understood. We established a method to visualize postnatally generated GCs in organotypic entorhino-hippocampal slice cultures (OTCs) using retroviral (RV) GFP-labeling and performed time-lapse imaging to study their morphological development in vitro. Using anterograde tracing we could, furthermore, demonstrate that the postnatally generated GCs in OTCs, similar to adult born GCs, grow into an existing entorhino-dentate circuitry. RV-labeled GCs were identified and individual cells were followed for up to four weeks post injection. Postnatally born GCs exhibited highly dynamic structural changes, including dendritic growth spurts but also retraction of dendrites and phases of dendritic stabilization. In contrast, older, presumably prenatally born GCs labeled with an adeno-associated virus (AAV), were far less dynamic. We propose that the high degree of structural flexibility seen in our preparations is necessary for the integration of newborn granule cells into an already existing neuronal circuit of the dentate gyrus in which they have to compete for entorhinal input with cells generated and integrated earlier. PMID:28256620

Effect of methylphenidate on ICU and hospital length of stay in patients with severe and moderate traumatic brain injury.

PubMed

Moein, Houshang; Khalili, Hossein A; Keramatian, Kamyar

2006-09-01

Traumatic brain injury is one of the major causes of death and disability among young people. Methylphenidate, a neural stimulant and protective drug, which has been mainly used for childhood attention deficit/hyperactivity disorder, has shown some benefits in late psychosocial problems in patients with traumatic brain injury. Its effect on arousal and consciousness has been also revealed in the sub-acute phase of traumatic brain injury. We studied its effect on the acute phase of moderate and severe traumatic brain injury (TBI) in relation to the length of ICU and hospital admission. Severely and moderately TBI patients (according to inclusion and exclusion criteria) were randomized to treatment and control groups. The treatment group received methylphenidate 0.3mg/kg per dose PO BID by the second day of admission until the time of discharge, and the control group received a placebo. Admission information and daily Glasgow Coma Scale (GCS) were recorded. Medical, surgical, and discharge plans for patients were determined by the attending physician, blinded to the study. Forty patients with severe TBI (GCS = 5-8) and 40 moderately TBI patients (GCS = 9-12) were randomly divided into treatment and control groups on the day of admission. In the severely TBI patients, both hospital and ICU length of stay, on average, were shorter in the treatment group compared with the control group. In the moderately TBI patients while ICU stay was shorter in the treatment group, there was no significant reduction of the period of hospitalization. There were no significant differences between the treatment and control groups in terms of age, sex, post resuscitation GCS, or brain CT scan findings, in either severely or moderately TBI patients. Methylphenidate was associated with reductions in ICU and hospital length of stay by 23% in severely TBI patients (P = 0.06 for ICU and P = 0.029 for hospital stay time). However, in the moderately TBI patients who received methylphenidate, there was 26% fall (P = 0.05) only in ICU length of stay.

Low-mass X-ray binaries from black hole retaining globular clusters

NASA Astrophysics Data System (ADS)

Giesler, Matthew; Clausen, Drew; Ott, Christian D.

2018-06-01

Recent studies suggest that globular clusters (GCs) may retain a substantial population of stellar-mass black holes (BHs), in contrast to the long-held belief of a few to zero BHs. We model the population of BH low-mass X-ray binaries (BH-LMXBs), an ideal observable proxy for elusive single BHs, produced from a representative group of Milky Way GCs with variable BH populations. We simulate the formation of BH binaries in GCs through exchange interactions between binary and single stars in the company of tens to hundreds of BHs. Additionally, we consider the impact of the BH population on the rate of compact binaries undergoing gravitational wave driven mergers. The characteristics of the BH-LMXB population and binary properties are sensitive to the GCs structural parameters as well as its unobservable BH population. We find that GCs retaining ˜1000 BHs produce a galactic population of ˜150 ejected BH-LMXBs, whereas GCs retaining only ˜20 BHs produce zero ejected BH-LMXBs. Moreover, we explore the possibility that some of the presently known BH-LMXBs might have originated in GCs and identify five candidate systems.

5-HT1A Receptors on Mature Dentate Gyrus Granule Cells are Critical for the Antidepressant Response

PubMed Central

Samuels, Benjamin Adam; Anacker, Christoph; Hu, Alice; Levinstein, Marjorie R.; Pickenhagen, Anouchka; Tsetsenis, Theodore; Madroñal, Noelia; Donaldson, Zoe R.; Drew, Liam John; Dranovsky, Alex; Gross, Cornelius T.; Tanaka, Kenji F.; Hen, René

2015-01-01

Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants, but the mechanisms by which they influence behavior are only partially resolved. Adult hippocampal neurogenesis is necessary for some of the responses to SSRIs, but it is unknown whether the mature dentate gyrus granule cells (mature DG GCs) also contribute. We deleted Serotonin 1A receptor (5HT1AR; a receptor required for the SSRI response) specifically from DG GCs and found that the effects of the SSRI fluoxetine on behavior and the Hypothalamic-Pituitary-Adrenal (HPA) axis were abolished. By contrast, mice lacking 5HT1ARs only in young adult born granule cells (abGCs) showed normal fluoxetine responses. Importantly, 5HT1AR deficient mice engineered to express functional 5HT1ARs only in DG GCs responded to fluoxetine, indicating that 5HT1ARs in DG GCs are sufficient to mediate an antidepressant response. Taken together, these data indicate that both mature DG GCs and young abGCs must be engaged for an antidepressant response. PMID:26389840

Are third-generation cephalosporins still the empirical antibiotic treatment of community-acquired spontaneous bacterial peritonitis? A systematic review and meta-analysis.

PubMed

Fiore, Marco; Gentile, Ivan; Maraolo, Alberto E; Leone, Sebastiano; Simeon, Vittorio; Chiodini, Paolo; Pace, Maria C; Gustot, Thierry; Taccone, Fabio S

2018-03-01

Spontaneous bacterial peritonitis (SBP) is a common complication among cirrhotic patients. Guidelines recommend third-generation cephalosporins (3GCs) as empiric antibiotic therapy (EAT) of SBP. Recently, a broad-spectrum EAT was shown to be more effective than cephalosporins in the treatment of nosocomial spontaneous bacterial peritonitis (N-SBP); however, the prevalence of 3GCs-resistant bacteria is high in the nosocomial setting and broad-spectrum EAT cannot be used in all cases of SBP. The aim of this study was to evaluate the 3GCs resistance distribution between N-SBP and community-acquired spontaneous bacterial peritonitis (CA-SBP) to clarify whether 3GCs are still an effective therapeutic intervention for CA-SBP. We searched for studies that reported the aetiology of SBP and the resistance profile of both gram-positive and gram-negative bacteria in MEDLINE and Google Scholar databases (since 1 January 2000 to 30 April 2017). A meta-analysis was carried out to estimate the risk difference [relative risk (RR) and 95% confidence intervals (CIs)] for 3GCs resistance in N-SBP and CA-SBP. Heterogeneity was assessed using the I-test. A total of eight studies were included, including 1074 positive cultures of ascitic fluid in cirrhotic patients; 462 positive cultures were from N-SBP and, among these, 251 (54.3%) were 3GCs resistant. Six hundred and twelve positive cultures were from CA-SBP and, among these, 207 (33.8%) were 3GCs-resistant SBP. A pooled RR of 3GCs resistance in N-SBP compared with CA-SBP showed a significant difference (RR=1.67, 95% CI: 1.14-2.44; P=0.008). We carried out two subgroup analyses: the first according to the median year of study observation (before vs. since 2008) and the second according to the country of the study (China vs. others). The studies carried out before 2008 (327 SBP-positive culture) showed a significantly higher risk for 3GCs-resistant strains in N-SBP compared with CA-SBP (RR=2.36, 95% CI: 1.39-3.99; P=0.001), whereas this was not found in SBP acquired after 2008 (RR=1.24, 95% CI: 0.83-1.84; P=0.29). N-SBP occurring in China had no significantly higher risk for 3GCs-resistant strains compared with CA-SBP (RR=1.44, 95% CI: 0.87-2.37; P=0.16). Our findings suggest that although the pooled RR of 3GCs resistance in N-SBP compared with CA-SBP show that 3GCs are still an effective option for the treatment of CA-SBP, the subanalysis of studies that enroled patients in the last decade did not show a significant higher RR of 3GCs resistance in N-SBP compared with CA-SBP. Therefore, in centres where local patterns of antimicrobial susceptibility (with low rates of 3GCs resistance) are not available, 3GCs should not be used initially for CA-SBP treatment. Future studies are needed to confirm this trend of 3GCs resistance.

Cryptic glucocorticoid receptor-binding sites pervade genomic NF-κB response elements.

PubMed

Hudson, William H; Vera, Ian Mitchelle S de; Nwachukwu, Jerome C; Weikum, Emily R; Herbst, Austin G; Yang, Qin; Bain, David L; Nettles, Kendall W; Kojetin, Douglas J; Ortlund, Eric A

2018-04-06

Glucocorticoids (GCs) are potent repressors of NF-κB activity, making them a preferred choice for treatment of inflammation-driven conditions. Despite the widespread use of GCs in the clinic, current models are inadequate to explain the role of the glucocorticoid receptor (GR) within this critical signaling pathway. GR binding directly to NF-κB itself-tethering in a DNA binding-independent manner-represents the standing model of how GCs inhibit NF-κB-driven transcription. We demonstrate that direct binding of GR to genomic NF-κB response elements (κBREs) mediates GR-driven repression of inflammatory gene expression. We report five crystal structures and solution NMR data of GR DBD-κBRE complexes, which reveal that GR recognizes a cryptic response element between the binding footprints of NF-κB subunits within κBREs. These cryptic sequences exhibit high sequence and functional conservation, suggesting that GR binding to κBREs is an evolutionarily conserved mechanism of controlling the inflammatory response.

Parapatric speciation in three islands: dynamics of geographical configuration of allele sharing

PubMed Central

Iwasa, Yoh

2017-01-01

We studied the time to speciation by geographical isolation for a species living on three islands connected by rare migration. We assumed that incompatibility was controlled by a number of quantitative loci and that individuals differing in loci by more than a threshold did not mix genetically with each other. For each locus, we defined the geographical configuration (GC), which specifies islands with common alleles, and traced the stochastic transitions between different GCs. From these results, we calculated the changes in genetic distances. As a single migration event provides an opportunity for transitions in multiple loci, the GCs of different loci are correlated, which can be evaluated by constructing the stochastic differential equations of the number of loci with different GCs. Our model showed that the low number of incompatibility loci facilitates parapatric speciation and that migrants arriving as a group shorten the waiting time to speciation compared with the same number of migrants arriving individually. We also discuss how speciation rate changes with geographical structure. PMID:28386439

Hepatic growth hormone and glucocorticoid receptor signaling in body growth, steatosis and metabolic liver cancer development

PubMed Central

Mueller, Kristina M.; Themanns, Madeleine; Friedbichler, Katrin; Kornfeld, Jan-Wilhelm; Esterbauer, Harald; Tuckermann, Jan P.; Moriggl, Richard

2012-01-01

Growth hormone (GH) and glucocorticoids (GCs) are involved in the control of processes that are essential for the maintenance of vital body functions including energy supply and growth control. GH and GCs have been well characterized to regulate systemic energy homeostasis, particular during certain conditions of physical stress. However, dysfunctional signaling in both pathways is linked to various metabolic disorders associated with aberrant carbohydrate and lipid metabolism. In liver, GH-dependent activation of the transcription factor signal transducer and activator of transcription (STAT) 5 controls a variety of physiologic functions within hepatocytes. Similarly, GCs, through activation of the glucocorticoid receptor (GR), influence many important liver functions such as gluconeogenesis. Studies in hepatic Stat5 or GR knockout mice have revealed that they similarly control liver function on their target gene level and indeed, the GR functions often as a cofactor of STAT5 for GH-induced genes. Gene sets, which require physical STAT5–GR interaction, include those controlling body growth and maturation. More recently, it has become evident that impairment of GH-STAT5 signaling in different experimental models correlates with metabolic liver disease, ranging from hepatic steatosis to hepatocellular carcinoma (HCC). While GH-activated STAT5 has a protective role in chronic liver disease, experimental disruption of GC-GR signaling rather seems to ameliorate metabolic disorders under metabolic challenge. In this review, we focus on the current knowledge about hepatic GH-STAT5 and GC-GR signaling in body growth, metabolism, and protection from fatty liver disease and HCC development. PMID:22564914

Assessment of Myocardial Infarct Size by Three-Dimensional and Two-Dimensional Speckle Tracking Echocardiography: A Comparative Study to Single Photon Emission Computed Tomography.

PubMed

Wang, Qiushuang; Huang, Dangsheng; Zhang, Liwei; Shen, Dong; Ouyang, Qiaohong; Duan, Zhongxiang; An, Xiuzhi; Zhang, Meiqing; Zhang, Chunhong; Yang, Feifei; Zhi, Guang

2015-10-01

To compare three-dimensional (3D) and two-dimensional (2D) speckle tracking echocardiography (STE) techniques in the assessment of left ventricular function and myocardial infarct size (MIS). Thirty-two patients diagnosed with ST elevation myocardial infarction and 18 healthy control patients underwent 2D echocardiography, 3D echocardiography, and single photon emission computed tomography (SPECT). 3D left ventricular global area strain (GAS), 2D and 3D global longitudinal strain (GLS), global radial strain (GRS) as well as global circumferential strain (GCS) were analyzed to correlate with myocardial infarct size detected by SPECT. 2D and 3D left ventricular ejection fraction (LVEF) as well as 2D and 3D wall motion score index (WMSI) also were measured using conventional echocardiography. The 2D-GLS values were significantly higher than that of 3D-GLS, while 2D-GCS and GRS were significantly lower than 3D-GCS and GRS, respectively. However, no significant differences in LVEF and WMSI could be observed between 2D and 3D echocardiography. Myocardial strain indices, LVEF, and WMSI using 2D and 3D echocardiography also had good correlations with MIS as measured by SPECT. ROC curve analysis showed that the 3D and 2D myocardial indices, LVEF, and WMSI could distinguish between small and large MIS, while 2D-GLS had the highest AUC. The 2D and 3D myocardial strain indices correlated well with MIS by SPECT. Among them, the 2D-GLS showed the highest diagnostic value, while 3D-GRS and GCS had better diagnostic value than 2D-GRS and GCS. © 2015, Wiley Periodicals, Inc.

Time matters - acute stress response and glucocorticoid sensitivity in early multiple sclerosis.

PubMed

Kern, Simone; Rohleder, Nicolas; Eisenhofer, Graeme; Lange, Jan; Ziemssen, Tjalf

2014-10-01

Psychosocial stress has frequently been associated with disease activity and acute exacerbations in multiple sclerosis (MS). Despite this well established finding, strikingly little is known about the acute hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) stress response in MS. Twenty-six early relapsing-remitting MS (RRMS) patients and seventeen age- and sex-matched healthy control subjects (CS) took part in the Trier Social Stress Test (TSST), a well validated psycho-social laboratory stress protocol. Repeated blood samples were analyzed for stress-related cortisol and catecholamine levels as well as for glucocorticoid sensitivity (GCS) of target immune cells. Chronic and acute stress appraisals were assessed by self-report measures. RRMS patients and CS did not differ in stress-related cortisol/catecholamine levels, GCS or stress appraisal in response to the TSST. However, cortisol release as well as GCS was strongly correlated with time since diagnosis but not with neurological disability. Patients with shorter disease duration (2-12 months) expressed a significantly higher cortisol stress response while MS patients with longer disease duration (14-36 months) showed a significantly diminished HPA response as well as lower post-stress GCS. There is evidence for a time-dependent variability in the HPA stress system with an increased cortisol stress response in the first year after diagnosis along with a more blunted HPA stress response and a diminished GCS in subsequent disease stages. Data underscore the highly dynamic nature of HPA axis regulation in the MS disease process, which could possibly relate to compensatory mechanisms within a cytokine-HPA axis feedback circuit model. Copyright © 2014 Elsevier Inc. All rights reserved.

Molecular Physiology of Membrane Guanylyl Cyclase Receptors.

PubMed

Kuhn, Michaela

2016-04-01

cGMP controls many cellular functions ranging from growth, viability, and differentiation to contractility, secretion, and ion transport. The mammalian genome encodes seven transmembrane guanylyl cyclases (GCs), GC-A to GC-G, which mainly modulate submembrane cGMP microdomains. These GCs share a unique topology comprising an extracellular domain, a short transmembrane region, and an intracellular COOH-terminal catalytic (cGMP synthesizing) region. GC-A mediates the endocrine effects of atrial and B-type natriuretic peptides regulating arterial blood pressure/volume and energy balance. GC-B is activated by C-type natriuretic peptide, stimulating endochondral ossification in autocrine way. GC-C mediates the paracrine effects of guanylins on intestinal ion transport and epithelial turnover. GC-E and GC-F are expressed in photoreceptor cells of the retina, and their activation by intracellular Ca(2+)-regulated proteins is essential for vision. Finally, in the rodent system two olfactorial GCs, GC-D and GC-G, are activated by low concentrations of CO2and by peptidergic (guanylins) and nonpeptidergic odorants as well as by coolness, which has implications for social behaviors. In the past years advances in human and mouse genetics as well as the development of sensitive biosensors monitoring the spatiotemporal dynamics of cGMP in living cells have provided novel relevant information about this receptor family. This increased our understanding of the mechanisms of signal transduction, regulation, and (dys)function of the membrane GCs, clarified their relevance for genetic and acquired diseases and, importantly, has revealed novel targets for therapies. The present review aims to illustrate these different features of membrane GCs and the main open questions in this field. Copyright © 2016 the American Physiological Society.

Contribution of glucocorticoids and glucocorticoid receptors to the regulation of neurodegenerative processes.

PubMed

Vyas, Sheela; Maatouk, Layal

2013-12-01

Isolation of glucocorticoids (GCs) from adrenal glands followed by synthesis led rapidly to their first clinical application, about 70 years ago, for treatment of rheumatoid arthritis. To this day GCs are used in diseases that have an inflammatory component. However, their use is carefully monitored because of harmful side effects. GCs are also synonymous with stress and adaptation. In CNS, GC binds and activates high affinity mineralocorticoid receptor (MR) and low affinity glucocorticoid receptor (GR). GR, whose expression is ubiquitous, is only activated when GC levels rise as during circadian peak and in response to stress. Numerous recent studies have yielded important and new insights on the mechanisms concerning pulsatile secretory pattern of GCs as well as various processes that tightly control their synthesis via hypothalamic-pituitary-adrenal (HPA) axis involving regulated release of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) from hypothalamus and pituitary, respectively. GR modulates neuronal functions and viability through both genomic and non-genomic actions, and importantly its transcriptional regulatory activity is tightly locked with GC secretory pattern. There is increasing evidence pointing to involvement of GC-GR in neurodegenerative disorders. Patients with Alzheimer's or Parkinson's or Huntington's disease show chronically high cortisol levels suggesting changes occurring in controls of HPA axis. In experimental models of these diseases, chronic stress or GC treatment was found to exacerbate both the clinical symptoms and neurodegenerative processes. However, recent evidence also shows that GC-GR can exert neuroprotective effects. Thus, for any potential therapeutic strategies in these neurodegenerative diseases we need to understand the precise modifications both in HPA axis and in GR activity and find ways to harness their protective actions.

The anti-Müllerian hormone (AMH) acts as a gatekeeper of ovarian steroidogenesis inhibiting the granulosa cell response to both FSH and LH.

PubMed

Sacchi, Sandro; D'Ippolito, Giovanni; Sena, Paola; Marsella, Tiziana; Tagliasacchi, Daniela; Maggi, Elena; Argento, Cindy; Tirelli, Alessandra; Giulini, Simone; La Marca, Antonio

2016-01-01

Anti Müllerian Hormone (AMH) has a negative and inhibitory role in many functions of human granulosa-lutein cells (hGCs) including notoriously the reduction of the aromatase CYP19A1 expression induced by follicle-stimulating hormone (FSH). No data have been provided on the possible role of AMH in modulating the response to luteinizing hormone (LH) (alone or combined with FSH) as well as its effect on other enzymes involved in steroidogenesis including aromatase P450scc. The aim of this study was to investigate the role of AMH as regulator of the basal and stimulated steroids production by hGCs. Primary culture of hGCs were incubated with hormones AMH, LH, and FSH, alone or in combination. The CYP19A1 and P450scc messenger RNA (mRNA) expression, normalized by housekeeping ribosomal protein S7 (RpS7) gene, was evaluated by reverse transcriptase quantitative PCR (RT-qPCR). Each reaction was repeated in triplicate. Negative controls using corresponding amount of vehicle control for each hormone treatment were performed. AMH did not modulate the basal mRNA expression of both aromatase genes at any of the concentrations tested. Meanwhile, the strong mRNA induction of CYP19A1 and P450scc generated by a 24-h gonadotropin treatment (alone and combined) was suppressed by 20 ng/ml AMH added to culture medium. These findings contribute in clarifying the relationship between hormones regulating the early phase of steroidogenesis confirming that AMH is playing a suppressive role on CYP19A1 expression stimulated by gonadotropin in hGCs. Furthermore, a similar inhibitory effect for AMH was observed on P450scc gene expression when activated by gonadotropin treatment.

Prenatal betamethasone does not affect glutamatergic or GABAergic neurogenesis in preterm newborns

PubMed Central

Vose, Linnea R.; Vinukonda, Govindaiah; Diamond, Daniel; Korumilli, Ritesh; Hu, Furong; Zia, Muhammad TK; Hevner, Robert; Ballabh, Praveen

2014-01-01

Prenatal glucocorticoids (GCs) are routinely used for pregnant women in preterm labor to prevent respiratory distress syndrome and intraventricular hemorrhage in premature infants. However, the effect of antenatal GCs on neurogenesis in preterm neonates remains elusive. Herein, we hypothesized that prenatal GCs might suppress both glutamatergic and GABAergic neurogenesis in preterm rabbits and that this treatment would induce distinct changes in the expression of transcription factors regulating these developmental events. To test our hypotheses, we treated pregnant rabbits with betamethasone at E27 and E28, delivered the pups at E29 (term=32d), and assessed neurogenesis at birth and postnatal day 3. We quantified radial glia (Sox2+) and intermediate progenitor cells (Tbr2+) in the dorsal cortical subventricular zone to assess glutamatergic neuronal progenitors, and counted Nkx2.1+ and Dlx2+ cells in the ganglionic eminence to evaluate GABAergic neurogenesis. In addition, we assayed transcription factors regulating neurogenesis. We found that prenatal GCs did not affect the densities of radial glia and intermediate progenitors of glutamatergic or GABAergic neurons. The number of GABA+ interneurons in the ganglionic eminence was similar between the prenatal GC treated pups compared to untreated controls. Moreover, the mRNA expression of transcription factors, including Pax6, Ngn1/2, Emx1/2, Insm1, Dlx1, Nkx2.1, and Gsh2, were comparable between the two groups. However, there was a transient elevation in Mash1 protein in betamethasone treated pups relative to controls at birth. This data suggests that prenatal GC treatment does not significantly impact the balance of glutamatergic and GABAergic neurogenesis in premature infants. PMID:24735821

THE NEXT GENERATION VIRGO CLUSTER SURVEY. VI. THE KINEMATICS OF ULTRA-COMPACT DWARFS AND GLOBULAR CLUSTERS IN M87

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

Zhang, Hong-Xin; Peng, Eric W.; Li, Biao

2015-03-20

The origin of ultra-compact dwarfs (UCDs; r{sub h} ≳ 10 pc)—objects larger and more massive than typical globular clusters (GCs), but more compact than typical dwarf galaxies—has been hotly debated in the 15 years since their discovery. Even whether UCDs should be considered galactic in origin, or simply the most extreme star clusters, is not yet settled. We present the dynamical properties of 97 spectroscopically confirmed UCDs and 911 GCs associated with the central cD galaxy of the Virgo cluster, M87. Our UCDs, of which 89% have M {sub *} ≳ 2× 10{sup 6} M {sub ☉} and 92% are as blue asmore » the classic blue GCs, nearly triple the confirmed sample of Virgo UCDs, providing by far the best opportunity for studying global dynamics of a UCD system. We found that (1) UCDs have a surface number density profile that is shallower than that of blue GCs in the inner ∼70 kpc and as steep as that of red GCs at larger radii; (2) UCDs exhibit a significantly stronger rotation than GCs, and blue GCs seem to have a velocity field that is more consistent with that of the surrounding dwarf ellipticals than with that of UCDs; (3) UCDs have an orbital anisotropy profile that is tangentially biased at radii ≲40 kpc and radially biased farther out, whereas blue GCs become more tangentially biased at larger radii beyond ∼40 kpc; (4) GCs with M {sub *} ≳ 2 × 10{sup 6} M {sub ☉} have rotational properties indistinguishable from the less massive ones, suggesting that it is the size, instead of mass, that differentiates UCDs from GCs as kinematically distinct populations. We conclude that most UCDs in M87 are not consistent with being merely the most luminous and extended examples of otherwise normal GCs. The radially biased orbital structure of UCDs at large radii is in general agreement with the 'tidally threshed dwarf galaxy' scenario.« less

Feminizing Genital Gender-Confirmation Surgery.

PubMed

Hadj-Moussa, Miriam; Ohl, Dana A; Kuzon, William M

2018-02-14

For many patients with gender dysphoria, gender-confirmation surgery (GCS) helps align their physical characteristics with their gender identity and is a fundamental element of comprehensive treatment. This article is the 2nd in a 3-part series about the treatment of gender dysphoria. Non-operative management was covered in part 1. This section begins broadly by reviewing surgical eligibility criteria, benefits of GCS, and factors associated with regret for transgender men and women. Then, the scope narrows to focus on aspects of feminizing genital GCS, including a discussion of vaginoplasty techniques, complications, and sexual function outcomes. Part 3 features operative considerations for masculinizing genital GCS. To summarize the World Professional Association for Transgender Health's (WPATH) surgical eligibility criteria and describe how patients with gender dysphoria benefit from GCS, provide an overview of genital and non-genital feminizing gender-confirmation procedures, and review vaginoplasty techniques, preoperative considerations, complications, and outcomes. A review of relevant literature through April 2017 was performed using PubMed. Review of literature related to surgical eligibility criteria for GCS, benefits of GCS, and surgical considerations for feminizing genitoplasty. Most transgender men and women who satisfy WPATH eligibility criteria experience improved quality of life, overall happiness, and sexual function after GCS; regret is rare. Penile inversion vaginoplasty is the preferred technique for feminizing genital GCS according to most surgeons, including the authors whose surgical technique is described. Intestinal vaginoplasty is reserved for certain scenarios. After vaginoplasty most patients report overall high satisfaction with their sexual function even when complications occur, because most are minor and easily treatable. GCS alleviates gender dysphoria for appropriately selected transgender men and women. Preoperative, intraoperative, and postoperative considerations of feminizing genital gender-confirmation procedures were reviewed. Hadj-Moussa M, Ohl DA, Kuzon WM. Feminizing Genital Gender-Confirmation Surgery. Sex Med Rev 2018;XX:XXX-XXX. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

A study to explore nurses' knowledge in using the Glasgow Coma Scale in an acute care hospital.

PubMed

Mattar, Ihsan; Liaw, Sok Ying; Chan, Moon Fai

2013-10-01

The Glasgow Coma Scale (GCS) is a neurological instrument, which measures the "depth and duration of impaired consciousness." The appeal of the GCS lies in its applicability in a wide variety of clinical situations as well as its ease of use by a range of healthcare staff. However, the GCS is not without its weaknesses and limitations. Its ease of use opens it up to misinterpretation and misapplication. Despite the propensity for incorrect assessment, the GCS remains in use in the clinical setting and enjoys an "unwarranted and privileged position." This creates an issue to patient care as the GCS is an important instrument in communicating an accurate assessment of the patient's condition between clinical staff. The aim of this study was to investigate nurses' knowledge in using the GCS and the demographic factors influencing knowledge of the GCS. This is a correlational observational study conducted in one acute care hospital in Singapore. The participants were registered nurses involving in bedside nursing care. A self-administered questionnaire was provided to the participants via ward managers. The quantitative responses were collated and analyzed using SPSS 16.0. Type of clinical discipline (i.e., neuroscience, general medicine, and neurointensive care unit; beta = 0.51, p < .001) and the length of experience in a neuroscience setting (beta = 0.22, p = .005) were significant in determining a nurses' knowledge of the GCS. Nurses in the neonatal intensive care unit scored the highest mean scores (12.7), whereas nurses from the general medicine wards scored the lowest mean scores (9.7). Nurses who worked in a neuroscience setting for 6 years or more scored higher mean scores (11.9) on the knowledge scale, whereas nurses who worked in a neuroscience setting for less than a year scored lower mean scores (10.0). Educational interventions and guidelines in performing GCS assessment are suggested to maintain and improve knowledge in performing the GCS.

Binding Affinity of Glycoconjugates to BACILLUS Spores and Toxins

NASA Astrophysics Data System (ADS)

Rasol, Aveen; Eassa, Souzan; Tarasenko, Olga

2010-04-01

Early recognition of Bacillus cereus group species is important since they can cause food-borne illnesses and deadly diseases in humans. Glycoconjugates (GCs) are carbohydrates covalently linked to non-sugar moieties including lipids, proteins or other entities. GCs are involved in recognition and signaling processes intrinsic to biochemical functions in cells. They also stimulate cell-cell adhesion and subsequent recognition and activation of receptors. We have demonstrated that GCs are involved in Bacillus cereus spore recognition. In the present study, we have investigated whether GCs possess the ability to bind and recognize B. cereus spores and Bacillus anthracis recombinant single toxins (sTX) and complex toxins (cTX). The affinity of GCs to spores + sTX and spores + cTX toxins was studied in the binding essay. Our results demonstrated that GC9 and GC10 were able to selectively bind to B. cereus spores and B. anthracis toxins. Different binding affinities for GCs were found toward Bacillus cereus spores + sTX and spores + cTX. Dilution of GCs does not impede the recognition and binding. Developed method provides a tool for simultaneous recognition and targeting of spores, bacteria toxins, and/or other entities.

Arabidopsis HAP2/GCS1 is a gamete fusion protein homologous to somatic and viral fusogens

PubMed Central

Valansi, Clari; Moi, David; Leikina, Evgenia; Matveev, Elena; Chernomordik, Leonid V.

2017-01-01

Cell–cell fusion is inherent to sexual reproduction. Loss of HAPLESS 2/GENERATIVE CELL SPECIFIC 1 (HAP2/GCS1) proteins results in gamete fusion failure in diverse organisms, but their exact role is unclear. In this study, we show that Arabidopsis thaliana HAP2/GCS1 is sufficient to promote mammalian cell–cell fusion. Hemifusion and complete fusion depend on HAP2/GCS1 presence in both fusing cells. Furthermore, expression of HAP2 on the surface of pseudotyped vesicular stomatitis virus results in homotypic virus–cell fusion. We demonstrate that the Caenorhabditis elegans Epithelial Fusion Failure 1 (EFF-1) somatic cell fusogen can replace HAP2/GCS1 in one of the fusing membranes, indicating that HAP2/GCS1 and EFF-1 share a similar fusion mechanism. Structural modeling of the HAP2/GCS1 protein family predicts that they are homologous to EFF-1 and viral class II fusion proteins (e.g., Zika virus). We name this superfamily Fusexins: fusion proteins essential for sexual reproduction and exoplasmic merger of plasma membranes. We suggest a common origin and evolution of sexual reproduction, enveloped virus entry into cells, and somatic cell fusion. PMID:28137780

Globular cluster formation and evolution in the context of cosmological galaxy assembly: open questions

NASA Astrophysics Data System (ADS)

Forbes, Duncan A.; Bastian, Nate; Gieles, Mark; Crain, Robert A.; Kruijssen, J. M. Diederik; Larsen, Søren S.; Ploeckinger, Sylvia; Agertz, Oscar; Trenti, Michele; Ferguson, Annette M. N.; Pfeffer, Joel; Gnedin, Oleg Y.

2018-02-01

We discuss some of the key open questions regarding the formation and evolution of globular clusters (GCs) during galaxy formation and assembly within a cosmological framework. The current state of the art for both observations and simulations is described, and we briefly mention directions for future research. The oldest GCs have ages greater than or equal to 12.5 Gyr and formed around the time of reionization. Resolved colour-magnitude diagrams of Milky Way GCs and direct imaging of lensed proto-GCs at z˜6 with the James Webb Space Telescope (JWST) promise further insight. GCs are known to host multiple populations of stars with variations in their chemical abundances. Recently, such multiple populations have been detected in ˜2 Gyr old compact, massive star clusters. This suggests a common, single pathway for the formation of GCs at high and low redshift. The shape of the initial mass function for GCs remains unknown; however, for massive galaxies a power-law mass function is favoured. Significant progress has been made recently modelling GC formation in the context of galaxy formation, with success in reproducing many of the observed GC-galaxy scaling relations.

Mucoadhesive properties and interaction with P-glycoprotein (P-gp) of thiolated-chitosans and -glycol chitosans and corresponding parent polymers: a comparative study.

PubMed

Trapani, Adriana; Palazzo, Claudio; Contino, Marialessandra; Perrone, Maria Grazia; Cioffi, Nicola; Ditaranto, Nicoletta; Colabufo, Nicola Antonio; Conese, Massimo; Trapani, Giuseppe; Puglisi, Giovanni

2014-03-10

The aim of the present work was to compare the mucoadhesive and efflux pump P-glycoprotein (P-gp) interacting properties of chitosan (CS)- and glycolchitosan (GCS)-based thiomers and corresponding unmodified parent polymers. For this purpose, the glycol chitosan-N-acetyl-cysteine (GCS-NAC) and glycol chitosan-glutathione (GCS-GSH) thiomers were prepared under simple and mild conditions. Their mucoadhesive characteristics were studied by turbidimetric and zeta potential measurements. The P-gp interacting properties were evaluated measuring the effects of thiolated- and unmodified-polymers on the bidirectional transport (BA/AB) of rhodamine-123 across Caco-2 cells as well as in the calcein-AM and ATPase activity assays. Although all the thiomers and unmodified polymers showed optimal-excellent mucoadhesive properties, the best mucoadhesive performances have been obtained by CS and CS-based thiomers. Moreover, it was found that the pretreatment of Caco-2 cell monolayer with GCS-NAC or GCS restores Rho-123 cell entrance by inhibiting P-gp activity. Hence, GCS-NAC and GCS may constitute new biomaterials useful for improving the bioavailability of P-gp substrates.

Globular clusters in high-redshift dwarf galaxies: a case study from the Local Group

NASA Astrophysics Data System (ADS)

Zick, Tom O.; Weisz, Daniel R.; Boylan-Kolchin, Michael

2018-06-01

We present the reconstructed evolution of rest-frame ultraviolet (UV) luminosities of the most massive Milky Way dwarf spheroidal satellite galaxy, Fornax, and its five globular clusters (GCs) across redshift, based on analysis of the stellar fossil record and stellar population synthesis modelling. We find that (1) Fornax's (proto-)GCs can generate 10-100 times more UV flux than the field population, despite comprising <˜{5} per cent of the stellar mass at the relevant redshifts; (2) due to their respective surface brightnesses, it is more likely that faint, compact sources in the Hubble Frontier Fields (HFFs) are GCs hosted by faint galaxies, than faint galaxies themselves. This may significantly complicate the construction of a galaxy UV luminosity function at z > 3. (3) GC formation can introduce order-of-magnitude errors in abundance matching. We also find that some compact HFF objects are consistent with the reconstructed properties of Fornax's GCs at the same redshifts (e.g. surface brightness, star formation rate), suggesting we may have already detected proto-GCs in the early Universe. Finally, we discuss the prospects for improving the connections between local GCs and proto-GCs detected in the early Universe.

Globular cluster formation and evolution in the context of cosmological galaxy assembly: open questions.

PubMed

Forbes, Duncan A; Bastian, Nate; Gieles, Mark; Crain, Robert A; Kruijssen, J M Diederik; Larsen, Søren S; Ploeckinger, Sylvia; Agertz, Oscar; Trenti, Michele; Ferguson, Annette M N; Pfeffer, Joel; Gnedin, Oleg Y

2018-02-01

We discuss some of the key open questions regarding the formation and evolution of globular clusters (GCs) during galaxy formation and assembly within a cosmological framework. The current state of the art for both observations and simulations is described, and we briefly mention directions for future research. The oldest GCs have ages greater than or equal to 12.5 Gyr and formed around the time of reionization. Resolved colour-magnitude diagrams of Milky Way GCs and direct imaging of lensed proto-GCs at z ∼6 with the James Webb Space Telescope (JWST) promise further insight. GCs are known to host multiple populations of stars with variations in their chemical abundances. Recently, such multiple populations have been detected in ∼2 Gyr old compact, massive star clusters. This suggests a common, single pathway for the formation of GCs at high and low redshift. The shape of the initial mass function for GCs remains unknown; however, for massive galaxies a power-law mass function is favoured. Significant progress has been made recently modelling GC formation in the context of galaxy formation, with success in reproducing many of the observed GC-galaxy scaling relations.

Globular cluster formation and evolution in the context of cosmological galaxy assembly: open questions

PubMed Central

Bastian, Nate; Gieles, Mark; Crain, Robert A.; Kruijssen, J. M. Diederik; Larsen, Søren S.; Ploeckinger, Sylvia; Agertz, Oscar; Trenti, Michele; Ferguson, Annette M. N.; Pfeffer, Joel; Gnedin, Oleg Y.

2018-01-01

We discuss some of the key open questions regarding the formation and evolution of globular clusters (GCs) during galaxy formation and assembly within a cosmological framework. The current state of the art for both observations and simulations is described, and we briefly mention directions for future research. The oldest GCs have ages greater than or equal to 12.5 Gyr and formed around the time of reionization. Resolved colour-magnitude diagrams of Milky Way GCs and direct imaging of lensed proto-GCs at z∼6 with the James Webb Space Telescope (JWST) promise further insight. GCs are known to host multiple populations of stars with variations in their chemical abundances. Recently, such multiple populations have been detected in ∼2 Gyr old compact, massive star clusters. This suggests a common, single pathway for the formation of GCs at high and low redshift. The shape of the initial mass function for GCs remains unknown; however, for massive galaxies a power-law mass function is favoured. Significant progress has been made recently modelling GC formation in the context of galaxy formation, with success in reproducing many of the observed GC-galaxy scaling relations. PMID:29507511

Glucosylceramide is Critical for Cell-Type Differentiation and Organogenesis, but not for Cell Viability in Arabidopsis

PubMed Central

Msanne, Joseph; Chen, Ming; Luttgeharm, Kyle D.; Bradley, Amanda M.; Mays, Elizabeth S.; Paper, Janet M.; Boyle, Daniel L.; Cahoon, Rebecca E.; Schrick, Kathrin; Cahoon, Edgar B.

2015-01-01

Summary Glucosylceramides (GlcCer), glucose-conjugated sphingolipids, are major components of the endomembrane system and plasma membrane in most eukaryote cells. Yet, the quantitative significance and cellular functions of GlcCer are not well characterized in plants and other multi-organ eukaryotes. To address this, we examined Arabidopsis lines lacking or deficient in GlcCer by insertional disruption or by RNAi suppression of the single gene for GlcCer synthase (GCS, At2g19880), the enzyme that catalyzes GlcCer synthesis. Null mutants for GCS (designated “gcs-1”) were viable as seedlings, albeit strongly reduced in size, and failed to develop beyond the seedling stage. Heterozygous plants harboring the insertion allele exhibited reduced transmission through the male gametophyte. Undifferentiated calli generated from gcs-1 seedlings and lacking GlcCer proliferated in a manner similar to calli from wild-type plants. However, gcs-1 calli, in contrast to wild-type calli, were unable to develop organs on differentiation media. Consistent with a role for GlcCer in organ-specific cell differentiation, calli from gcs-1 mutants formed roots and leaves on media supplemented with the glucosylated sphingosine glucopsychosine, which was readily converted to GlcCer independent of GCS. Underlying these phenotypes, gcs-1 cells had altered Golgi morphology and fewer cisternae per Golgi apparatus relative to wild-type cells, indicative of protein trafficking defects. Despite seedling lethality in the null mutant, GCS RNAi suppression lines with ≤2% of wild-type GlcCer levels were viable and fertile. Collectively, these results indicate that GlcCer are essential for cell-type differentiation and organogenesis, and plant cells produce GlcCer amounts in excess of that required for normal development. PMID:26313010

A Two-Center Validation of "Patient Does Not Follow Commands" and Three Other Simplified Measures to Replace the Glasgow Coma Scale for Field Trauma Triage.

PubMed

Hopkins, Emily; Green, Steven M; Kiemeney, Michael; Haukoos, Jason S

2018-05-02

Out-of-hospital personnel worldwide calculate the 13-point Glasgow Coma Scale (GCS) score as a routine part of field trauma triage. We wish to independently validate a simpler binary assessment to replace the GCS for this task. We analyzed trauma center registries from Loma Linda University Health (2003 to 2015) and Denver Health Medical Center (2009 to 2015) to compare the binary assessment "patient does not follow commands" (ie, GCS motor score <6) with GCS score less than or equal to 13 for the prediction of 5 trauma outcomes: emergency intubation, clinically significant brain injury, need for neurosurgical intervention, Injury Severity Score greater than 15, and mortality. As a secondary analysis, we similarly evaluated 3 other measures simpler than the GCS: GCS motor score less than 5, Simplified Motor Score, and the "alert, voice, pain, unresponsive" scale. In this analysis of 47,973 trauma patients, we found that the binary assessment "patient does not follow commands" was essentially identical to GCS score less than or equal to 13 for the prediction of all 5 trauma outcomes, with slightly superior positive likelihood ratios (eg, those for mortality 2.37 versus 2.13) offsetting slightly inferior negative ones (eg, those for mortality 0.25 versus 0.24) and its graphic depiction of sensitivity versus specificity superimposing the GCS prediction curve. We found similar results for the 3 other simplified measures. In this 2-center external validation, we confirmed that a simple binary assessment-"patient does not follow commands"-could effectively replace the more complicated GCS for field trauma triage. Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Emerging Genetic Counselor Roles within the Biotechnology and Pharmaceutical Industries: as Industry Interest Grows in Rare Genetic Disorders, How are Genetic Counselors Joining the Discussion?

PubMed

Field, Tessa; Brewster, Stephanie Jo; Towne, Meghan; Campion, MaryAnn W

2016-08-01

Traditionally, the biotechnology and pharmaceutical industry (BPI) has focused drug development at the mass-market level targeting common medical issues. However, a recent trend is the development of therapies for orphan or rare disorders, including many genetic disorders. Developing treatments for genetic disorders requires an understanding of the needs of the community and translating genomic information to clinical and non-clinical audiences. The core skills of genetic counselors (GCs) include a deep knowledge of genetics and ability to communicate complex information to a broad audience, making GCs a choice fit for this shift in drug development. To date there is limited data defining the roles GCs hold within this industry. This exploratory study aimed to define the roles and motivation of GCs working in BPI, assess job satisfaction, and identify translatable skills and current gaps in GC training programs. The authors surveyed 26 GCs working in BPI in the United States; 79 % work for companies focused on rare disorders. GC positions in BPI are growing, with 57 % of respondents being the first GC in their role. GCs in BPI continue to utilize core genetic counseling competencies, though 72 % felt their training did not fully prepare them for BPI. These data suggest opportunities for exposure to BPI in GC training to better prepare future generations of GCs for these career opportunities. GC satisfaction was high in BPI, notably in areas traditionally reported as less satisfying on the National Society for Genetic Counselors Professional Status Survey: salary and advancement opportunities. BPI's growing interest in rare disorders represents a career opportunity for GCs, addressing both historic areas of dissatisfaction for GCs and BPI's genomic communication needs.

Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation.

PubMed

Chowdhury, Indrajit; Thomas, Kelwyn; Zeleznik, Anthony; Thompson, Winston E

2016-05-01

Published results from our laboratory identified prohibitin (PHB), a gene product expressed in granulosa cells (GCs) that progressively increases during follicle maturation. Our current in vitro studies demonstrate that follicle-stimulating hormone (FSH) stimulates Phb expression in rat primary GCs. The FSH-dependent expression of PHB was primarily localized within mitochondria, and positively correlates with the morphological changes in GCs organelles, and synthesis and secretions of estradiol (E2) and progesterone (P4). In order to confirm that PHB plays a regulatory role in rat GC differentiation, endogenous PHB-knockdown studies were carried out in undifferentiated GCs using adenoviral (Ad)-mediated RNA interference methodology. Knockdown of PHB in GCs resulted in the suppression of the key steroidogenic enzymes including steroidogenic acute regulatory protein (StAR), p450 cholesterol side-chain cleavage enzyme (p450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), and aromatase (Cyp19a1); and decreased E2 and P4 synthesis and secretions in the presence of FSH stimulation. Furthermore, these experimental studies also provided direct evidence that PHB within the mitochondrial fraction in GCs is phosphorylated at residues Y249, T258, and Y259 in response to FSH stimulation. The observed levels of phosphorylation of PHB at Y249, T258, and Y259 were significantly low in GCs in the absence of FSH stimulation. In addition, during GC differentiation FSH-induced expression of phospho-PHB (pPHB) requires the activation of MEK1-ERK1/2 signaling pathway. Taken together, these studies provide new evidence supporting FSH-dependent PHB/pPHB upregulation in GCs is required to sustain the differentiated state of GCs. © 2016 The authors.

Multivariate outcome prediction in traumatic brain injury with focus on laboratory values.

PubMed

Nelson, David W; Rudehill, Anders; MacCallum, Robert M; Holst, Anders; Wanecek, Michael; Weitzberg, Eddie; Bellander, Bo-Michael

2012-11-20

Traumatic brain injury (TBI) is a major cause of morbidity and mortality. Identifying factors relevant to outcome can provide a better understanding of TBI pathophysiology, in addition to aiding prognostication. Many common laboratory variables have been related to outcome but may not be independent predictors in a multivariate setting. In this study, 757 patients were identified in the Karolinska TBI database who had retrievable early laboratory variables. These were analyzed towards a dichotomized Glasgow Outcome Scale (GOS) with logistic regression and relevance vector machines, a non-linear machine learning method, univariately and controlled for the known important predictors in TBI outcome: age, Glasgow Coma Score (GCS), pupil response, and computed tomography (CT) score. Accuracy was assessed with Nagelkerke's pseudo R². Of the 18 investigated laboratory variables, 15 were found significant (p<0.05) towards outcome in univariate analyses. In contrast, when adjusting for other predictors, few remained significant. Creatinine was found an independent predictor of TBI outcome. Glucose, albumin, and osmolarity levels were also identified as predictors, depending on analysis method. A worse outcome related to increasing osmolarity may warrant further study. Importantly, hemoglobin was not found significant when adjusted for post-resuscitation GCS as opposed to an admission GCS, and timing of GCS can thus have a major impact on conclusions. In total, laboratory variables added an additional 1.3-4.4% to pseudo R².

ESCRT-II controls retinal axon growth by regulating DCC receptor levels and local protein synthesis

PubMed Central

Konopacki, Filip A.; Dwivedy, Asha; Bellon, Anaïs; Blower, Michael D.

2016-01-01

Endocytosis and local protein synthesis (LPS) act coordinately to mediate the chemotropic responses of axons, but the link between these two processes is poorly understood. The endosomal sorting complex required for transport (ESCRT) is a key regulator of cargo sorting in the endocytic pathway, and here we have investigated the role of ESCRT-II, a critical ESCRT component, in Xenopus retinal ganglion cell (RGC) axons. We show that ESCRT-II is present in RGC axonal growth cones (GCs) where it co-localizes with endocytic vesicle GTPases and, unexpectedly, with the Netrin-1 receptor, deleted in colorectal cancer (DCC). ESCRT-II knockdown (KD) decreases endocytosis and, strikingly, reduces DCC in GCs and leads to axon growth and guidance defects. ESCRT-II-depleted axons fail to turn in response to a Netrin-1 gradient in vitro and many axons fail to exit the eye in vivo. These defects, similar to Netrin-1/DCC loss-of-function phenotypes, can be rescued in whole (in vitro) or in part (in vivo) by expressing DCC. In addition, ESCRT-II KD impairs LPS in GCs and live imaging reveals that ESCRT-II transports mRNAs in axons. Collectively, our results show that the ESCRT-II-mediated endocytic pathway regulates both DCC and LPS in the axonal compartment and suggest that ESCRT-II aids gradient sensing in GCs by coupling endocytosis to LPS. PMID:27248654

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

Wang Qiushi; Peng, Eric W.; Blakeslee, John P.

We study the azimuthal distribution of globular clusters (GCs) in early-type galaxies and compare them to their host galaxies using data from the ACS Virgo Cluster Survey. We find that in host galaxies with visible elongation ({epsilon} > 0.2) and intermediate to high luminosities (M{sub z} < -19), the GCs are preferentially aligned along the major axis of the stellar light. The red (metal-rich) GC subpopulations show strong alignment with the major axis of the host galaxy, which supports the notion that these GCs are associated with metal-rich field stars. The metal-rich GCs in lenticular galaxies show signs of beingmore » more strongly associated with disks rather than bulges. Surprisingly, we also find that the blue (metal-poor) GCs can also show the same correlation. If the metal-poor GCs are part of the early formation of the halo and built up through mergers, then our results support a picture where halo formation and merging occur anisotropically, and that the present-day major axis is an indicator of the preferred merging axis.« less

Glasgow Coma Scale and Its Components on Admission: Are They Valuable Prognostic Tools in Acute Mixed Drug Poisoning?

PubMed Central

Eizadi Mood, N.; Sabzghabaee, A. M.; Yadegarfar, Gh.; Yaraghi, A.; Ramazani Chaleshtori, M.

2011-01-01

Introduction. The verbal, eye, and motor components of Glasgow coma scale (GCS) may be influenced by poisoned patients' behavior in an attempted suicide. So, the values of admission GCS and its components for outcomes prediction in mixed drugs poisoning were investigated. Materials and Methods. A followup study data was performed on patients with mixed drugs poisoning. Outcomes were recorded as without complications and with complications. Discrimination was evaluated by calculating the area under the receiver operating characteristic curves (AUC). Results. There was a significant difference between the mean value of each component of GCS as well as the total GCS between patients with and without complication. Discrimination was best for GCS (AUC: 0.933 ± 0.020) and verbal (0.932 ± 0.021), followed by motor (0.911 ± 0.025), then eye (0.89 ± 0.028). Conclusions. Admission GCS and its components seem to be valuable in outcome prediction of patients with mixed drug poisoning. PMID:21559299

Glycoconjugates as Mediators of Nitric Oxide Production upon Exposure to Bacterial Spores by Macrophages

NASA Astrophysics Data System (ADS)

Lahiani, Mohamed; Soderberg, Lee; Tarasenko, Olga

2011-06-01

Phagocytes generate nitric oxide (NO) in large quantities to combat bacteria. The spore-producing Gram-positive organisms of Bacillus cereus family are causative agents from mild to a life threatening infection in humans and domestic animals. Our group have shown that glycoconjugates (GCs) activate macrophages and enhance killing of Bacillus spores. In this investigation, we will explore the effect of different GCs structures on NO production. The objective of this study is to study effects of GCs 2, 4, 6, 8, 10 on NO release upon exposure to B. cereus and Bacillus anthracis spores by macrophages. Our results demonstrated that GCs activated macrophages and increased NO production using studied GCs ligands compared to macrophage only (p<0.001). GC2 and GC8 were able to further increase NO production in macrophages compared to the B. anthracis spores treated macrophages (p<0.001). Our finding suggests that GCs could be used as potential mediators of NO production in macrophages to fight B. anthracis and other pathogens.

Unique Fe2P Nanoparticles Enveloped in Sandwichlike Graphited Carbon Sheets as Excellent Hydrogen Evolution Reaction Catalyst and Lithium-Ion Battery Anode.

PubMed

Zhang, Yan; Zhang, Huijuan; Feng, Yangyang; Liu, Li; Wang, Yu

2015-12-09

The novel Fe2P nanoparticles encapsulated in sandwichlike graphited carbon envelope nanocomposite (Fe2P/GCS) that can be first applied in hydrogen evolution reaction (HER) as well as lithium-ion batteries (LIBs) has been designed and fabricated. The unique sandwiched Fe2P/GCS is characterized with several prominent merits, including large specific surface area, nanoporous structure, excellent electronic conductivity, enhanced structural integrity and so on. All of these endow the Fe2P/GCS with brilliant electrochemical performance. When used as a HER electrocatalyst in acidic media, the harvested Fe2P/GCS demonstrates low onset overpotential and Tafel slope as well as particularly outstanding durability. Moreover, as an anode material for LIBs, the sandwiched Fe2P/GCS presents high specific capacity and excellent cyclability and rate capability. As a consequence, the acquired Fe2P/GCS is a promising material for energy applications, especially HER and LIBs.

A Comparative Study of Glasgow Coma Scale and Full Outline of Unresponsiveness Scores for Predicting Long-Term Outcome After Brain Injury.

PubMed

McNett, Molly M; Amato, Shelly; Philippbar, Sue Ann

2016-01-01

The aim of this study was to compare predictive ability of hospital Glasgow Coma Scale (GCS) scores and scores obtained using a novel coma scoring tool (the Full Outline of Unresponsiveness [FOUR] scale) on long-term outcomes among patients with traumatic brain injury. Preliminary research of the FOUR scale suggests that it is comparable with GCS for predicting mortality and functional outcome at hospital discharge. No research has investigated relationships between coma scores and outcome 12 months postinjury. This is a prospective cohort study. Data were gathered on adult patients with traumatic brain injury admitted to urban level I trauma center. GCS and FOUR scores were assigned at 24 and 72 hours and at hospital discharge. Glasgow Outcome Scale scores were assigned at 6 and 12 months. The sample size was n = 107. Mean age was 53.5 (SD = ±21, range = 18-91) years. Spearman correlations were comparable and strongest among discharge GCS and FOUR scores and 12-month outcome (r = .73, p < .000; r = .72, p < .000). Multivariate regression models indicate that age and discharge GCS were the strongest predictors of outcome. Areas under the curve were similar for GCS and FOUR scores, with discharge scores occupying the largest areas. GCS and FOUR scores were comparable in bivariate associations with long-term outcome. Discharge coma scores performed best for both tools, with GCS discharge scores predictive in multivariate models.

The Little Engines That Could? Globular Clusters Contribute Significantly to Reionization-era Star Formation

NASA Astrophysics Data System (ADS)

Boylan-Kolchin, Michael

2018-06-01

Metal-poor globular clusters (GCs) are both numerous and ancient, which indicates that they may be important contributors to ionizing radiation in the reionization era. Starting from the observed number density and stellar mass function of old GCs at z = 0, I compute the contribution of GCs to ultraviolet luminosity functions (UVLFs) in the high-redshift Universe (10 ≳ z ≳ 4). Even under absolutely minimal assumptions - no disruption of GCs and no reduction in GC stellar mass from early times to the present - GC star formation contributes non-negligibly to the UVLF at luminosities that are accessible to the Hubble Space Telescope (HST; M1500 ≈ -17). If the stellar masses of GCs were significantly higher in the past, as is predicted by most models explaining GC chemical anomalies, then GCs dominate the UV emission from many galaxies in existing deep-field observations. On the other hand, it is difficult to reconcile observed UVLFs with models requiring stellar masses at birth that exceed present-day stellar masses by more than a factor of 5. The James Webb Space Telescope (JWST) will be able to directly detect individual GCs at z ˜ 6 in essentially all bright galaxies, and many galaxies below the knee of the UVLF, for most of the scenarios considered here. The properties of a subset of high-redshift sources with -19 ≲ M_{1500} ≲ -14 in HST lensing fields indicate that they may actually be GCs in formation.

Detailed abundance analysis of globular clusters in the Local Group. NGC 147, NGC 6822, and Messier 33

NASA Astrophysics Data System (ADS)

Larsen, S. S.; Brodie, J. P.; Wasserman, A.; Strader, J.

2018-06-01

Context. Globular clusters (GCs) are emerging as powerful tracers of the chemical composition of extragalactic stellar populations. Aims: We present new abundance measurements for 11 GCs in the Local Group galaxies NGC 147, NGC 6822, and Messier 33. These are combined with previously published observations of four GCs in the Fornax and Wolf-Lundmark-Melotte (WLM) galaxies. Methods: The abundances were determined from analyses of integrated-light spectra obtained with the HIRES spectrograph on the Keck I telescope and with UVES on the Very Large Telescope (VLT). We used our analysis technique that was developed for this purpose and tested on Milky Way GCs. Results: We find that the clusters with [Fe/H] < -1.5 are all α-enhanced at about the same level as Milky Way GCs. Their Na abundances are also generally enhanced relative to Milky Way halo stars, suggesting that these extragalactic GCs resemble their Milky Way counterparts in containing large numbers of Na-rich stars. For [Fe/H] > -1.5, the GCs in M33 are also α-enhanced, while the GCs that belong to dwarfs (NGC 6822 SC7 and Fornax 4) have closer to solar-scaled α-element abundances. The abundance patterns in SC7 are remarkably similar to those in the Galactic GC Ruprecht 106, including significantly subsolar [Na/Fe] and [Ni/Fe] ratios. In NGC 147, the GCs with [Fe/H] < -2.0 account for about 6% of the total luminosity of stars in the same metallicity range, a lower fraction than those previously found in the Fornax and WLM galaxies, but substantially higher than in the Milky Way halo. Conclusions: At low metallicities, the abundance patterns suggest that GCs in the Milky Way, dwarf galaxies, and M33 experienced similar enrichment histories and/or processes. At higher metallicities, the lower levels of α-enhancement in the GCs found in dwarf galaxies resemble the abundance patterns observed in field stars in nearby dwarfs. Constraining the presence of multiple populations in these GCs is complicated by lack of information about detailed abundances in field stars of the corresponding metallicities. We suggest that correlations such as [Na/Fe] versus [Ni/Fe] may prove useful for this purpose if an accuracy of 0.1 dex or better can be reached for integrated-light measurements. Tables A.1-A.15 (individual abundance measurements) are only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/613/A56

Quantitative analysis of development and aging of genital corpuscles in glans penis of the rat.

PubMed

Shiino, Mizuho; Hoshi, Hideo; Kawashima, Tomokazu; Ishikawa, Youichi; Takayanagi, Masaaki; Murakami, Kunio; Kishi, Kiyoshi; Sato, Fumi

2015-02-01

The aim of the present postnatal developmental study was to determine densities of unique genital corpuscles (GCs) in glans penis of developing and aged rats. GCs were identified as corpuscular endings consisting of highly branched and coiled axons with many varicosities, which were immunoreactive for protein gene product 9.5. In addition, GCs were immunoreactive for calcitonin gene-related peptide and substance P, but not for vasoactive intestinal polypeptide and neuropeptide Y. GCs were not found in the glans penis of 1 week old rats. Densities of GCs were low at 3 weeks, significantly increased at 5 and 10 weeks, reached the peak of density at 40 weeks, and tended to decrease at 70 and 100 weeks. Sizes of GCs were small in 3 weeks old rats, increased at 5 and 10 weeks, reached the peak-size at 40 weeks and reduced in size at 70 and 100 weeks. Considering sexual maturation of the rat, the results reveal that GCs of the rat begins to develop postnatal and reaches to the peak of their development after puberty and continues to exist until old age, in contrast to prenatal and early postnatal development of other sensory receptors of glabrous skin. Copyright © 2014 Elsevier Ltd. All rights reserved.

Deep photometry of two accreted families of globular clusters in the remote M31 halo

NASA Astrophysics Data System (ADS)

Mackey, Dougal

2013-10-01

Globular clusters {GCs} are fossil relics from which we can obtain critical insights into the merger and accretion events that underlie hierarchical galaxy assembly. As part of the major Pan-Andromeda Archaeological Survey {PAndAS} we have discovered two groups of GCs that closely trace narrow stellar debris streams in the M31 halo. These clearly represent two distinct accreted families of GCs - the only known examples apart from the few Galactic GCs arriving with the Sagittarius dwarf. We propose to obtain deep ACS imaging of 14 GCs spanning these two accreted families, allowing us to measure the constituent stellar populations, line-of-sight distance, and structural parameters of each object. We will, for the first time, quantify the typical properties of accreted GCs in the M31 halo as well as the degree of variation amongst them, and how closely they correspond to the suspected accreted GC population in the Milky Way. Combined with new radial velocity measurements for the GCs, our proposed observations will allow us to trace the 3D orbits of the two streams within the M31 halo, and thus break the main degeneracies that plague numerical models designed to probe the gravitational potential and distribution of dark mass.

Glycoconjugates Effects: do Gender and Ethnicity Influence Exposure of Pathogen by Peripheral Mononuclear Cells ?

NASA Astrophysics Data System (ADS)

Lahiani, Mohamed; Tarasenko, Olga

2010-04-01

Members of the Bacillus cereus group demonstrate different pathological effects. B. cereus is a spore-forming, gram positive bacterium responsible for most foodborne illnesses. It was shown that susceptibility to infection and response to vaccines or treatments can be attributed to specific immunogenetic factors including gender and ethnicity. Glycoconjugate polymers (GCs) are potentially important in pharmaceutical and biomedical research. Our group has shown that GCs activate murine macrophages and promote killing of Bacillus cereus spores during phagocytosis. We hypothesized that the GCs effects are independent from gender and race. The goal of the present study was two-folds: A) determine whether GCs influence on human PMNC exposure of B. cereus spores and B) analyze whether gender and ethnicity influence of the effect of GCs. GCs were studied during exposure and post-exposure conditions. Phagocytosis was performed during exposure of PMNC to Bacillus spores. Post-exposure analysis involved cytotoxicity, cell viability and activation, and colonies forming unit. GC1 and GC3 enhance Bacillus spore killing. GC1 proved more effective than GC3 in spore killing while activating PMNC. Results demonstrate GCs effect were independent from ethnicity or gender. Findings of this research demonstrated that GC can be used as ligands to stimulate PMNC and kill B. cereus spores.

Development and Testing of a Two-UAV Communication Relay System.

PubMed

Li, Boyang; Jiang, Yifan; Sun, Jingxuan; Cai, Lingfeng; Wen, Chih-Yung

2016-10-13

In the development of beyond-line-of-sight (BLOS) Unmanned Aerial Vehicle (UAV) systems, communication between the UAVs and the ground control station (GCS) is of critical importance. The commonly used economical wireless modules are restricted by the short communication range and are easily blocked by obstacles. The use of a communication relay system provides a practical way to solve these problems, improving the performance of UAV communication in BLOS and cross-obstacle operations. In this study, a communication relay system, in which a quadrotor was used to relay radio communication for another quadrotor was developed and tested. First, the UAVs used as the airborne platform were constructed, and the hardware for the communication relay system was selected and built up. Second, a set of software programs and protocol for autonomous mission control, communication relay control, and ground control were developed. Finally, the system was fully integrated into the airborne platform and tested both indoor and in-flight. The Received Signal Strength Indication (RSSI) and noise value in two typical application scenarios were recorded. The test results demonstrated the ability of this system to extend the communication range and build communication over obstacles. This system also shows the feasibility to coordinate multiple UAVs' communication with the same relay structure.

Development and Testing of a Two-UAV Communication Relay System

PubMed Central

Li, Boyang; Jiang, Yifan; Sun, Jingxuan; Cai, Lingfeng; Wen, Chih-Yung

2016-01-01

In the development of beyond-line-of-sight (BLOS) Unmanned Aerial Vehicle (UAV) systems, communication between the UAVs and the ground control station (GCS) is of critical importance. The commonly used economical wireless modules are restricted by the short communication range and are easily blocked by obstacles. The use of a communication relay system provides a practical way to solve these problems, improving the performance of UAV communication in BLOS and cross-obstacle operations. In this study, a communication relay system, in which a quadrotor was used to relay radio communication for another quadrotor was developed and tested. First, the UAVs used as the airborne platform were constructed, and the hardware for the communication relay system was selected and built up. Second, a set of software programs and protocol for autonomous mission control, communication relay control, and ground control were developed. Finally, the system was fully integrated into the airborne platform and tested both indoor and in-flight. The Received Signal Strength Indication (RSSI) and noise value in two typical application scenarios were recorded. The test results demonstrated the ability of this system to extend the communication range and build communication over obstacles. This system also shows the feasibility to coordinate multiple UAVs’ communication with the same relay structure. PMID:27754369

Building the evidence base for REDD+: Study design and methods for evaluating the impacts of conservation interventions on local well-being

PubMed Central

Sills, Erin O.; de Sassi, Claudio; Jagger, Pamela; Lawlor, Kathleen; Miteva, Daniela A.; Pattanayak, Subhrendu K.; Sunderlin, William D.

2018-01-01

Climate change mitigation in developing countries is increasingly expected to generate co-benefits that help meet sustainable development goals. This has been an expectation and a hotly contested issue in REDD+ (reducing emissions from deforestation and forest degradation) since its inception. While the core purpose of REDD+ is to reduce carbon emissions, its legitimacy and success also depend on its impacts on local well-being. To effectively safeguard against negative impacts, we need to know whether and which well-being outcomes can be attributed to REDD+. Yet, distinguishing the effects of choosing particular areas for REDD+ from the effects of the interventions themselves remains a challenge. The Global Comparative Study (GCS) on REDD+ employed a quasi-experimental before-after-control-intervention (BACI) study design to address this challenge and evaluate the impacts of 16 REDD+ pilots across the tropics. We find that the GCS approach allows identification of control groups that represent the counterfactual, thereby permitting attribution of outcomes to REDD+. The GCS experience belies many of the common critiques of the BACI design, especially concerns about collecting baseline data on control groups. Our findings encourage and validate the early planning and up-front investments required to evaluate the local impacts of global climate change mitigation efforts with confidence. The stakes are high, both for the global environment and for local populations directly affected by those efforts. The standards for evidence should be concomitantly high. PMID:29681690

Building the evidence base for REDD+: Study design and methods for evaluating the impacts of conservation interventions on local well-being.

PubMed

Sills, Erin O; de Sassi, Claudio; Jagger, Pamela; Lawlor, Kathleen; Miteva, Daniela A; Pattanayak, Subhrendu K; Sunderlin, William D

2017-03-01

Climate change mitigation in developing countries is increasingly expected to generate co-benefits that help meet sustainable development goals. This has been an expectation and a hotly contested issue in REDD+ (reducing emissions from deforestation and forest degradation) since its inception. While the core purpose of REDD+ is to reduce carbon emissions, its legitimacy and success also depend on its impacts on local well-being. To effectively safeguard against negative impacts, we need to know whether and which well-being outcomes can be attributed to REDD+. Yet, distinguishing the effects of choosing particular areas for REDD+ from the effects of the interventions themselves remains a challenge. The Global Comparative Study (GCS) on REDD+ employed a quasi-experimental before-after-control-intervention (BACI) study design to address this challenge and evaluate the impacts of 16 REDD+ pilots across the tropics. We find that the GCS approach allows identification of control groups that represent the counterfactual, thereby permitting attribution of outcomes to REDD+. The GCS experience belies many of the common critiques of the BACI design, especially concerns about collecting baseline data on control groups. Our findings encourage and validate the early planning and up-front investments required to evaluate the local impacts of global climate change mitigation efforts with confidence. The stakes are high, both for the global environment and for local populations directly affected by those efforts. The standards for evidence should be concomitantly high.

Small Unmanned Aircraft Systems Integration into the National Airspace System Visual-Line-of-Sight Human-in-the-Loop Experiment

NASA Technical Reports Server (NTRS)

Trujillo, Anna C.; Ghatas, Rania W.; Mcadaragh, Raymon; Burdette, Daniel W.; Comstock, James R.; Hempley, Lucas E.; Fan, Hui

2015-01-01

As part of the Unmanned Aircraft Systems (UAS) in the National Airspace System (NAS) project, research on integrating small UAS (sUAS) into the NAS was underway by a human-systems integration (HSI) team at the NASA Langley Research Center. Minimal to no research has been conducted on the safe, effective, and efficient manner in which to integrate these aircraft into the NAS. sUAS are defined as aircraft weighing 55 pounds or less. The objective of this human system integration team was to build a UAS Ground Control Station (GCS) and to develop a research test-bed and database that provides data, proof of concept, and human factors guidelines for GCS operations in the NAS. The objectives of this experiment were to evaluate the effectiveness and safety of flying sUAS in Class D and Class G airspace utilizing manual control inputs and voice radio communications between the pilot, mission control, and air traffic control. The design of the experiment included three sets of GCS display configurations, in addition to a hand-held control unit. The three different display configurations were VLOS, VLOS + Primary Flight Display (PFD), and VLOS + PFD + Moving Map (Map). Test subject pilots had better situation awareness of their vehicle position, altitude, airspeed, location over the ground, and mission track using the Map display configuration. This configuration allowed the pilots to complete the mission objectives with less workload, at the expense of having better situation awareness of other aircraft. The subjects were better able to see other aircraft when using the VLOS display configuration. However, their mission performance, as well as their ability to aviate and navigate, was reduced compared to runs that included the PFD and Map displays.

The Impact of DMARD and Anti-TNF Therapy on Functional Characterization of Short-Term T-Cell Activation in Patients with Rheumatoid Arthritis – A Follow-Up Study

PubMed Central

Szalay, Balázs; Cseh, Áron; Mészáros, Gergő; Kovács, László; Balog, Attila; Vásárhelyi, Barna

2014-01-01

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a systemic dysfunction of T-cells. In this study we tested the impact of DMARD and anti-TNF agents on short-term activation characteristics of T-cells. We enrolled 12 patients with newly diagnosed RA (naïve RA) who were treated with methothrexate (MTX) and glucocorticsteroid (GCS) and 22 patients with established RA non responding to conventional DMARD therapy who were treated with different anti-TNF agents. Nine healthy volunteers served as controls. Blood samples were taken at baseline, then at 4th and 8th week of therapy. The characteristics of several intracellular activation processes during short-term activation of T-cells including cytoplasmic Ca2+ level, mitochondrial Ca2+ level, reactive oxygen species (ROS) and nitric oxide (NO) generation were determined by a novel flow-cytometry technique. At baseline, the tested processes were comparable to controls in naïve RA. During GCS therapy, cytoplasmic Ca2+ level and ROS generation decreased. After the addition of MTX to GCS cytoplasmic Ca2+ level became comparable to controls, while ROS generation decreased further. In DMARD non responders, cytoplasmic Ca2+ level was higher than controls at baseline. The cytoplasmic Ca2+ level became comparable to controls and ROS generation decreased during each of the three anti-TNF-α agent therapies. Mitochondrial Ca2+ level and NO generation were unaltered in all of the patient groups. These results indicate that intracellular machinery is affected in T-cells of RA patients. This may alter the behavior of T-cells during activation. Different therapeutic approaches may modulate the abnormal T-cell functions. PMID:25098248

Cooperation of international Research Infrastructures to address environmental global challenges

NASA Astrophysics Data System (ADS)

Bonet García, Francisco J.; Suárez-Muñoz, María; Conchubhair, Diarmuid O.; Dohna, Tina; Lo Bue, Nadia

2017-04-01

Human impact on the planet is causing a set of global environmental problems that threaten the wellbeing of current and future generations. Examples of these environmental problems include climate change, decline of biodiversity, alteration of biogeochemical cycles, ocean acidification, etc. These environmental Global Challenges (GCs) are transnational and complex, combining elements of both natural and social factors. Providing solutions for these challenges can be significantly enhanced through the collaboration of various related institutions, governments and stakeholders. A deeper understanding of the causes and consequences of GCs, as well as the processes which control them is required. Environmental Research Infrastructures (DANUBIUS-RI) are key players in this learning process. Covering many fields of research, it is through RIs collaboration that GCs can be more fully addressed. However, the collaboration among environmental RIs is still limited nationally as well as internationally. Although contact is encouraged and interactions are common practice, there are few cases where RI managers initiate and foster transnational collaborations in order to address specific problems. The COOP+ project aims to explore and strengthen cooperation among global RIs by bringing various RIs together and working on the identification of requirements, strengths, knowledge gaps and other relevant items in regard to the selected GCs. For this purpose, 13 GCs have been selected: coral bleaching, marine debris, noise impact on marine fauna, Arctic sea ice melting, pollinators decline, threatened species, agriculture pollutants, nitrogen cycle, carbon and GHG, geohazards and extreme events, estuaries, global urbanization process, and ozone depletion. These GCs are being analysed and described by multidisciplinary teams of experts composed of scientists, RIs operators and other stakeholders. This assessment will derive a list of tasks and requirements to be fulfilled by the participating RIs regarding each GC. Moreover, it is expected that the outcomes of this work will encourage and promote project participants and stakeholders, as well as the general public to take action with regard to the challenges and solutions outlined by the GC descriptions. This task of describing GCs is an open initiative: all input is welcome. To input with any suggestions, please send an email to info@coop-plus.eu. This contribution presents the preliminary results obtained during the description of the selected GC's under the point of view of RIs: - Template used to describe all GC in a standardized way. It contains several sections regarding topics such as: rationale of the challenge, identification of scientific/technical/social needs, role of RIs in the GC, tasks to be done (data collection, experimental research, modelling, dissemination), etc. - Configuration of working teams designed to describe the GCs. Each GC has a person in charge who is responsible of coordinating the writing process. The working team is composed by scientists experts in each challenge, experts in thematic RIs (within EU and abroad), policy makers and other stakeholders. The results obtained by this description task will be published in a special issue in a Geoscience journal. The writing teams are expected to become project consortia willing to participate in specific calls to address GCs.

Inter-rater reliability of the Full Outline of UnResponsiveness score and the Glasgow Coma Scale in critically ill patients: a prospective observational study

PubMed Central

2010-01-01

Introduction The Glasgow Coma Scale (GCS) is the most widely used scoring system for comatose patients in intensive care. Limitations of the GCS include the impossibility to assess the verbal score in intubated or aphasic patients, and an inconsistent inter-rater reliability. The FOUR (Full Outline of UnResponsiveness) score, a new coma scale not reliant on verbal response, was recently proposed. The aim of the present study was to compare the inter-rater reliability of the GCS and the FOUR score among unselected patients in general critical care. A further aim was to compare the inter-rater reliability of neurologists with that of intensive care unit (ICU) staff. Methods In this prospective observational study, scoring of GCS and FOUR score was performed by neurologists and ICU staff on 267 consecutive patients admitted to intensive care. Results In a total of 437 pair wise ratings the exact inter-rater agreement for the GCS was 71%, and for the FOUR score 82% (P = 0.0016); the inter-rater agreement within a range of ± 1 score point for the GCS was 90%, and for the FOUR score 92% (P = ns.). The exact inter-rater agreement among neurologists was superior to that among ICU staff for the FOUR score (87% vs. 79%, P = 0.04) but not for the GCS (73% vs. 73%). Neurologists and ICU staff did not significantly differ in the inter-rater agreement within a range of ± 1 score point for both GCS (88% vs. 93%) and the FOUR score (91% vs. 88%). Conclusions The FOUR score performed better than the GCS for exact inter-rater agreement, but not for the clinically more relevant agreement within the range of ± 1 score point. Though neurologists outperformed ICU staff with regard to exact inter-rater agreement, the inter-rater agreement of ICU staff within the clinically more relevant range of ± 1 score point equalled that of the neurologists. The small advantage in inter-rater reliability of the FOUR score is most likely insufficient to replace the GCS, a score with a long tradition in intensive care. PMID:20398274

Optical-near-IR analysis of globular clusters in the IKN dwarf spheroidal: a complex star formation history

NASA Astrophysics Data System (ADS)

Tudorica, A.; Georgiev, I. Y.; Chies-Santos, A. L.

2015-09-01

Context. Age, metallicity, and spatial distribution of globular clusters (GCs) provide a powerful tool for reconstructing major star-formation episodes in galaxies. IKN is a faint dwarf spheroidal (dSph) in the M 81 group of galaxies. It contains five old GCs, which makes it the galaxy with the highest known specific frequency (SN = 126). Aims: We estimate the photometric age, metallicity, and spatial distribution of the poorly studied IKN GCs. We search SDSS for GC candidates beyond the HST/ACS field of view, which covers half of IKN. Methods: To break the age-metallicity degeneracy in the colour, we used WHT/LIRIS KS-band photometry and derived photometric ages and metallicities by comparison with SSP models in the V,I,Ks colour space. Results: IKN GCs' VIKs colours are consistent with old ages (≥8 Gyr) and a metallicity distribution with a higher mean than is typical for such a dSph ([Fe/H] ≃ -1.4-0.2+0.6 dex). Their photometric mass range (0.5 < ℳGC< 4 × 105 M⊙) implies an unusually high mass ratio between GCs and field stars, of 10.6%. Mixture model analysis of the RGB field stars' metallicity suggests that 72% of the stars may have formed together with the GCs. Using the most massive GC-SFR relation, we calculated a star formation rate (SFR) of ~10 M⊙/yr during its formation epoch. We note that the more massive GCs are closer to the galaxy photometric centre. IKN GCs also appear spatially aligned along a line close to the major axis of the IKN and nearly orthogonal to the plane of spatial distribution of galaxies in the M 81 group. We identify one new IKN GC candidate based on colour and the PSF analysis of the SDSS data. Conclusions: The evidence of i) broad and high metallicity distribution of the field IKN RGB stars and its GCs, ii) high fraction, and iii) spatial alignment of IKN GCs supports a scenario for tidally triggered, complex IKN's star formation history in the context of interactions with galaxies in the M 81 group.

Review article: the investigation and management of gastric neuroendocrine tumours.

PubMed

Basuroy, R; Srirajaskanthan, R; Prachalias, A; Quaglia, A; Ramage, J K

2014-05-01

Gastric carcinoids (GCs) or neuroendocrine tumours (NETs) are increasingly identified at endoscopy, and account for 0.6-2% of all gastric polyps identified. The SEER database in the US has demonstrated a rising incidence of gastric NETs amongst all NETs; from 2.2% between 1950 and 1969 to 6.0% between 2000 and 2007. To review the literature and assist clinicians in managing patients with GCs. A literature search was conducted through MEDLINE using search terms: gastric, carcinoid, neuroendocrine tumour, therapy, endoscopy, mucosal resection, submucosal dissection. Relevant articles were identified through manual review. The reference lists of these articles were reviewed to include further appropriate articles. There are three types of GCs with important epidemiological, pathophysiological, histological and endoscopic differences that affect prognosis and management. Type 1 and 2 GCs develop in the context of hypergastrinaemia that originates from achlorhydria in atrophic gastritis and a gastrinoma, respectively. Type 3 GCs occur sporadically and independent of gastrin. The histological type, grade and Ki67 index are used to determine prognosis and direct clinical management. Type 1 GCs >1 cm in size and type 2 GCs should be assessed for invasion beyond the submucosa with EUS prior to endoscopic resection with EMR or ESD. Type 3 GCs should be managed as per recommendations for gastric adenocarcinoma. The treatment of advanced disease is multimodal. Patients with gastric carcinoids should be discussed in a specialist neuroendocrine tumour multidisciplinary meeting to ensure all treatment options are explored in localised and advanced disease. Areas of controversy exist that need further research. © 2014 John Wiley & Sons Ltd.

Histochemical Characterization of Oocytes in the Pink Cuskeel (Genypterus blacodes).

PubMed

Cohen, Stefanía; Petcoff, Gladys; Freijo, Roberto O; Portiansky, Enrique L; Barbeito, Claudio G; Macchi, Gustavo J; Díaz, Alcira O

2015-08-01

In the present study we histochemically and lectinhistochemically characterized the growing oocytes of the pink cuskeel (Genypterus blacodes). We used histochemical methods for the localization and characterization of glycoconjugates (GCs) and lectin histochemical techniques for the identification of specific sugar residues. We analyzed presence and distribution of GCs in the different structures of the growing follicles (cortical alveoli, globules, yolk granules and zona radiata). During the initial stage of vitellogenesis, the oocytes presented small yolk granules composed of GCs that gradually increased during exogenous vitellogenesis. These GCs contained moderate quantities of α-D-mannose, D-glucose, N-acetylglucosamine and N-acetyl-neuraminic acid. The cortical alveoli contained both neutral and carboxylated GCs, and lectin techniques detected N-acetylgalactosamine, galactose and L-fucose. The zona radiata showed a strong positive reaction to PAS and it reacted weakly with more specific techniques, such as KOH/PA*S and PA/Bh/KOH/PAS. This structure showed GCs with oxidizable vicinal diols, O-acyl sugars and sialic acid residues with different substitution types and presented N-acetylgalactosamine and L-fucose specific residues. The oocytes follicular envelope evidenced neutral and acidic non-sulfated GCs and high concentrations of α-D-mannose, D-glucose, galactose and N-acetylgalactosamine. The intergranular cytoplasmic GCs were mainly rich in α-D-mannose, D-glucose, N-acetylgalactosamine, N-acetylglucosamine and N-acetyl-neuraminic acid. These results enhance the comprehension of the structure and functionality of the pink cuskeel ovarian follicles, and provide a useful tool for the study of this tissue in other teleost species.

A Chandra Study of the Stellar X-Ray Emissivity of Globular Clusters in the M31 Bulge

NASA Astrophysics Data System (ADS)

Xu, Xiao-jie; Li, Zhiyuan

2018-03-01

The X-ray emissivity (i.e., luminosity per unit stellar mass) of globular clusters (GCs) is an important indicator of their dynamical evolution history. Based on deep archival Chandra observations, we report a stacking analysis of 44 GCs with 0.5–8 keV luminosities L X ≲ 1035 erg s‑1 in the M31 bulge, which are supposed to be dominated by cataclysmic variables (CVs) and coronally active binaries (ABs). We obtain a significant detection at the 5σ level in 0.5–8 keV band. The average X-ray luminosity per GC and the average X-ray emissivity are determined to be 5.3 ± 1.6 × 1033 erg s‑1 and 13.2 ± 4.3 × 1027 erg s‑1 {M}ȯ -1, respectively. Both of these values are consistent with those of Milky Way GCs. Moreover, the measured emissivity of M31 GCs is also consistent with that of the Milky Way field stars. Massive GCs have X-ray luminosities that are marginally higher than those of less massive ones. Massive GCs also show a lower emissivity (5.0+/- 2.5× {10}27 {erg} {{{s}}}-1 {M}ȯ -1) than less massive ones (26.5+/- 14.3× {10}27 {erg} {{{s}}}-1 {M}ȯ -1), which is consistent with the scenario that the (progenitors of) CVs and ABs were more efficiently destroyed via stellar encounters in the more massive GCs. No dependence of the X-ray emissivity on GC color or on the projected galactocentric distance of GCs is found.

Opposite Effects of Cortisol on Consolidation of Temporal Sequence Memory during Waking and Sleep

ERIC Educational Resources Information Center

Wilhelm, Ines; Wagner, Ullrich; Born, Jan

2011-01-01

Memory functions involve three stages: encoding, consolidation, and retrieval. Modulating effects of glucocorticoids (GCs) have been consistently observed for declarative memory with GCs enhancing encoding and impairing retrieval, but surprisingly, little is known on how GCs affect memory consolidation. Studies in rats suggest a beneficial effect…

Can Graduated Compressive Stockings Reduce Muscle Activity during Running?

ERIC Educational Resources Information Center

Lucas-Cuevas, Ángel Gabriel; Priego Quesada, José Ignacio; Giménez, José Vicente; Aparicio, Inmaculada; Cortell-Tormo, Juan Manuel; Pérez-Soriano, Pedro

2017-01-01

Purpose: Graduated compressive stockings (GCS) have been suggested to influence performance by reducing muscle oscillations and improving muscle function and efficiency. However, no study to date has analyzed the influence of GCS on muscle activity during running. The objective of the study was to analyze the influence of GCS on the perception of…

The Hypothalamic-Pituitary-Adrenal Axis and the Fetus.

PubMed

Morsi, Amr; DeFranco, Donald; Witchel, Selma

2018-06-06

Glucocorticoids (GCs), cortisol in humans, influence multiple essential maturational events during gestation. In the human fetus, fetal hypothalamic-pituitary-adrenal (HPA) axis function, fetal adrenal steroidogenesis, placental 11β- hydroxysteroid dehydrogenase type 2 activity, maternal cortisol concentrations, and environmental factors impact fetal cortisol exposure. The beneficial effects of synthetic glucocorticoids (sGCs), such as dexamethasone and betamethasone, on fetal lung maturation have significantly shifted the management of preterm labor and threatened preterm birth. Accumulating evidence suggests that exposure to sGCs in utero at critical developmental stages can alter the function of organ systems and that these effects may have sequelae that extend into adult life. Maternal stress and environmental influences may also impact fetal GC exposure. This article explores the vulnerability of the fetal HPA axis to endogenous GCs and exogenous sGCs. © 2018 S. Karger AG, Basel.

The outer halo globular cluster system of M31 - I. The final PAndAS catalogue

NASA Astrophysics Data System (ADS)

Huxor, A. P.; Mackey, A. D.; Ferguson, A. M. N.; Irwin, M. J.; Martin, N. F.; Tanvir, N. R.; Veljanoski, J.; McConnachie, A.; Fishlock, C. K.; Ibata, R.; Lewis, G. F.

2014-08-01

We report the discovery of 59 globular clusters (GCs) and two candidate GCs in a search of the halo of M31, primarily via visual inspection of Canada-France-Hawaii Telescope/MegaCam imagery from the Pan-Andromeda Archaeological Survey (PAndAS). The superior quality of these data also allows us to check the classification of remote objects in the Revised Bologna Catalogue (RBC), plus a subset of GC candidates drawn from Sloan Digital Sky Survey (SDSS) imaging. We identify three additional new GCs from the RBC, and confirm the GC nature of 11 SDSS objects (8 of which appear independently in our remote halo catalogue); the remaining 188 candidates across both lists are either foreground stars or background galaxies. Our new catalogue represents the first uniform census of GCs across the M31 halo - we find clusters to the limit of the PAndAS survey area at projected radii of up to Rproj ˜ 150 kpc. Tests using artificial clusters reveal that detection incompleteness cuts in at luminosities below MV = -6.0; our 50 per cent completeness limit is MV ≈ -4.1. We construct a uniform set of PAndAS photometric measurements for all known GCs outside Rproj = 25 kpc, and any new GCs within this radius. With these data, we update results from Huxor et al., investigating the luminosity function (LF), colours and effective radii of M31 GCs with a particular focus on the remote halo. We find that the GCLF is clearly bimodal in the outer halo (Rproj > 30 kpc), with the secondary peak at MV ˜ -5.5. We argue that the GCs in this peak have most likely been accreted along with their host dwarf galaxies. Notwithstanding, we also find, as in previous surveys, a substantial number of GCs with above-average luminosity in the outer M31 halo - a population with no clear counterpart in the Milky Way.

Foamed Cement Interactions with CO 2

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

Verba, Circe; Montross, Scott; Spaulding, Richard

2017-02-02

Geologic carbon storage (GCS) is a potentially viable strategy to reduce greenhouse emissions. Understanding the risks to engineered and geologic structures associated with GCS is an important first step towards developing practices for safe and effective storage. The widespread utilization of foamed cement in wells may mean that carbon dioxide (CO 2)/brine/foamed cement reactions may occur within these GCS sites. Characterizing the difference in alteration rates as well as the physical and mechanical impact of CO 2/brine/foamed cement is an important preliminary step to ensuring offshore and onshore GCS is a prudent anthropogenic CO 2 mitigation choice.

Validity and cultural equivalence of the standard Greene Climacteric Scale in Hong Kong.

PubMed

Chen, Run Qiu; Davis, Susan R; Wong, Chit Ming; Lam, Tai Hing

2010-01-01

The aim of this study was to translate the standard Greene Climacteric Scale (GCS) and a urogenital symptom scale into colloquial Chinese (Hong Kong) and test their validity and reliability in Hong Kong Chinese women. The scales were translated with standard techniques, and cross-cultural construct validity, internal consistency, test-retest reliability, and responsiveness were tested on samples of women aged 40 to 60 years recruited from the community. A total of 611 women, with mean (SD) age of 48.9 (5.3) years, provided completed scales for the study. Confirmatory factor analysis demonstrated construct validity of the translated standard GCS. The items were found to have good homogeneity in measuring the scale concepts (Cronbach alpha > 0.7). But the three-item urogenital scale had poor internal consistency (Cronbach alpha = 0.43), and a combination of this scale with the standard GCS resulted in a reduced model fit to the data. Test-retest reliability for the GCS was good on women recruited for a retest (n = 52). The translated GCS was found to be responsive to change over time (effect size, 0.59; n = 19). The Chinese (Hong Kong) version of the standard GCS is a valid and cultural-equivalent instrument. Our data do not support inclusion of the urogenital scale to the standard GCS. Measurement of urogenital symptoms is subject to further study.

PRIMORDIAL r-PROCESS DISPERSION IN METAL-POOR GLOBULAR CLUSTERS

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

Roederer, Ian U., E-mail: iur@obs.carnegiescience.edu

Heavy elements, those produced by neutron-capture reactions, have traditionally shown no star-to-star dispersion in all but a handful of metal-poor globular clusters (GCs). Recent detections of low [Pb/Eu] ratios or upper limits in several metal-poor GCs indicate that the heavy elements in these GCs were produced exclusively by an r-process. Re-examining GC heavy element abundances from the literature, we find unmistakable correlations between the [La/Fe] and [Eu/Fe] ratios in four metal-poor GCs (M5, M15, M92, and NGC 3201), only two of which were known previously. This indicates that the total r-process abundances vary from star to star (by factors ofmore » 2-6) relative to Fe within each GC. We also identify potential dispersion in two other GCs (M3 and M13). Several GCs (M12, M80, and NGC 6752) show no evidence of r-process dispersion. The r-process dispersion is not correlated with the well-known light element dispersion, indicating that it was present in the gas throughout the duration of star formation. The observations available at present suggest that star-to-star r-process dispersion within metal-poor GCs may be a common but not ubiquitous phenomenon that is neither predicted by nor accounted for in current models of GC formation and evolution.« less

VLT photometry in the Antlia cluster: the giant ellipticals NGC3258 and NGC3268 and their globular cluster systems

NASA Astrophysics Data System (ADS)

Bassino, Lilia P.; Richtler, Tom; Dirsch, Boris

2008-05-01

We present a deep Very Large Telescope (VLT) photometry in the regions surrounding the two dominant galaxies of the Antlia cluster, the giant ellipticals NGC3258 and NGC3268. We construct the luminosity functions of their globular cluster systems (GCSs) and determine their distances through the turn-over magnitudes. These distances are in good agreement with those obtained by the SBF method. There is some, but not conclusive, evidence that the distance to NGC3268 is larger by several Mpc. The GCSs colour distributions are bimodal but the brightest globular clusters (GCs) show a unimodal distribution with an intermediate colour peak. The radial distributions of both GCSs are well fitted by de Vaucouleurs laws up to 5arcmin. Red GCs present a steeper radial density profile than the blue GCs, and follow closely the galaxies' brightness profiles. Total GC populations are estimated to be about 6000 +/- 150GCs in NGC3258 and NGC4750 +/- 150GCs in NGC3268. We discuss the possible existence of GCs in a field located between the two giant galaxies (intracluster GCs). Their luminosity functions and number densities are consistent with the two GCSs overlapping in projection. Based on observations carried out at the European Southern Observatory, Paranal (Chile). Programme 71.B-0122(A). E-mail: lbassino@fcaglp.unlp.edu.ar (LPB); tom@mobydick.cfm.udec.cl (TR); borischacabuco@yahoo.co.uk (BD)

Impact of epigallocatechin‑3‑gallate on expression of nuclear factor erythroid 2‑related factor 2 and γ‑glutamyl cysteine synthetase genes in oxidative stress‑induced mouse renal tubular epithelial cells.

PubMed

Du, Xuanyi; Yu, Jinfeng; Sun, Xiaohan; Qu, Shaochuan; Zhang, Haitao; Hu, Mengying; Yang, Shufen; Zhou, Ping

2018-06-01

The aim of the present study was to investigate the antioxidant response mechanism of epigallocatechin‑3‑gallate (EGCG) in H2O2‑induced mouse renal tubular epithelial cells (MRTECs). The cultured MRTECs were divided into normal, H2O2 (control) and EGCG treatment groups. The MTT assay was used to assess cell viability, and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), immunocytochemical and western blot analyses were performed to detect the expression of nuclear factor erythroid 2‑related factor 2 (Nrf2) and γ‑glutamyl cysteine synthetase (γ‑GCS). EGCG was able to mitigate H2O2‑mediated cell damage. The RT‑qPCR results demonstrated that EGCG was able to upregulate the gene expression of Nrf2 and γ‑GCS in MRTECs in a dose‑dependent manner. The immunocytochemistry and western blot analyses demonstrated that EGCG was able to increase the protein expression of Nrf2 and γ‑GCS in MRTECs in a dose‑dependent manner. Oxidative stress may lead to a decrease in the viability of MRTECs, while EGCG was able to promote the expression of Nrf2 and γ‑GCS in MRTECs, thereby improving the antioxidant capacity of the cells and promoting the repair of oxidative stress injury.

Dendrites of dentate gyrus granule cells contribute to pattern separation by controlling sparsity

PubMed Central

Chavlis, Spyridon; Petrantonakis, Panagiotis C.

2016-01-01

ABSTRACT The hippocampus plays a key role in pattern separation, the process of transforming similar incoming information to highly dissimilar, nonverlapping representations. Sparse firing granule cells (GCs) in the dentate gyrus (DG) have been proposed to undertake this computation, but little is known about which of their properties influence pattern separation. Dendritic atrophy has been reported in diseases associated with pattern separation deficits, suggesting a possible role for dendrites in this phenomenon. To investigate whether and how the dendrites of GCs contribute to pattern separation, we build a simplified, biologically relevant, computational model of the DG. Our model suggests that the presence of GC dendrites is associated with high pattern separation efficiency while their atrophy leads to increased excitability and performance impairments. These impairments can be rescued by restoring GC sparsity to control levels through various manipulations. We predict that dendrites contribute to pattern separation as a mechanism for controlling sparsity. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:27784124

HUBBLE SPACE TELESCOPE SNAPSHOT SEARCH FOR PLANETARY NEBULAE IN GLOBULAR CLUSTERS OF THE LOCAL GROUP

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

Bond, Howard E., E-mail: heb11@psu.edu

2015-04-15

Single stars in ancient globular clusters (GCs) are believed incapable of producing planetary nebulae (PNs), because their post-asymptotic-giant-branch evolutionary timescales are slower than the dissipation timescales for PNs. Nevertheless, four PNs are known in Galactic GCs. Their existence likely requires more exotic evolutionary channels, including stellar mergers and common-envelope binary interactions. I carried out a snapshot imaging search with the Hubble Space Telescope (HST) for PNs in bright Local Group GCs outside the Milky Way. I used a filter covering the 5007 Å nebular emission line of [O iii], and another one in the nearby continuum, to image 66 GCs.more » Inclusion of archival HST frames brought the total number of extragalactic GCs imaged at 5007 Å to 75, whose total luminosity slightly exceeds that of the entire Galactic GC system. I found no convincing PNs in these clusters, aside from one PN in a young M31 cluster misclassified as a GC, and two PNs at such large angular separations from an M31 GC that membership is doubtful. In a ground-based spectroscopic survey of 274 old GCs in M31, Jacoby et al. found three candidate PNs. My HST images of one of them suggest that the [O iii] emission actually arises from ambient interstellar medium rather than a PN; for the other two candidates, there are broadband archival UV HST images that show bright, blue point sources that are probably the PNs. In a literature search, I also identified five further PN candidates lying near old GCs in M31, for which follow-up observations are necessary to confirm their membership. The rates of incidence of PNs are similar, and small but nonzero, throughout the GCs of the Local Group.« less

Globular Cluster Orbits from HST Proper Motions: Constraining the Formation and Mass of the Milky Way Halo

NASA Astrophysics Data System (ADS)

Sohn, S. Tony; Van Der Marel, Roeland P.; Deason, Alis J.; Bellini, Andrea; Besla, Gurtina; Watkins, Laura

2016-06-01

The globular cluster (GC) system of the Milky Way (MW) provides important information on the MW's present structure and past evolution. GCs in the halo are particularly useful tracers; because of their long dynamical timescales, their orbits retain imprints of their origin or accretion history. Full 3D motions are required to calculate past orbits. While most GCs have known line of sight velocities, accurate proper motion (PM) measurements are currently available for only a few halo GCs. Our goal is to create the first high-quality PM database for halo GCs. We have identified suitable 1st-epoch data in the HST Archive for 20 halo GCs at 10-100 kpc from the Galactic Center. We are in the process of obtaining the necessary 2nd-epoch data to determine absolute PMs of the target GCs through our HST program GO-14235. We will use the same advanced astrometric techniques that allowed us to measure the PMs of M31 and Leo I. Previous studies of the halo GC system based on e.g., stellar populations, metallicities, RR Lyrae properties, and structural properties have revealed a dichotomy between old and young halo GCs. This may reflect distinct formation scenarios (in situ vs. accreted). Orbit calculations based on our PMs will directly test this. The PMs will also yield the best handle yet on the velocity anisotropy profile of any tracer population in the halo. This will resolve the mass-anisotropy degeneracy to provide an improved estimate of the MW mass, which is at present poorly known. In summary, our project will deliver the first accurate PMs for halo GCs, and will significantly increase our understanding of the formation, evolution, and mass of the MW.

Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas

PubMed Central

Lin, Suling J; Gagnon-Bartsch, Johann A; Tan, Iain Beehuat; Earle, Sophie; Ruff, Louise; Pettinger, Katherine; Ylstra, Bauke; van Grieken, Nicole; Rha, Sun Young; Chung, Hyun Cheol; Lee, Ju-Seog; Cheong, Jae Ho; Noh, Sung Hoon; Aoyama, Toru; Miyagi, Yohei; Tsuburaya, Akira; Yoshikawa, Takaki; Ajani, Jaffer A; Boussioutas, Alex; Yeoh, Khay Guan; Yong, Wei Peng; So, Jimmy; Lee, Jeeyun; Kang, Won Ki; Kim, Sung; Kameda, Yoichi; Arai, Tomio; zur Hausen, Axel; Speed, Terence P; Grabsch, Heike I; Tan, Patrick

2015-01-01

Objective Differences in gastric cancer (GC) clinical outcomes between patients in Asian and non-Asian countries has been historically attributed to variability in clinical management. However, recent international Phase III trials suggest that even with standardised treatments, GC outcomes differ by geography. Here, we investigated gene expression differences between Asian and non-Asian GCs, and if these molecular differences might influence clinical outcome. Design We compared gene expression profiles of 1016 GCs from six Asian and three non-Asian GC cohorts, using a two-stage meta-analysis design and a novel biostatistical method (RUV-4) to adjust for technical variation between cohorts. We further validated our findings by computerised immunohistochemical analysis on two independent tissue microarray (TMA) cohorts from Asian and non-Asian localities (n=665). Results Gene signatures differentially expressed between Asians and non-Asian GCs were related to immune function and inflammation. Non-Asian GCs were significantly enriched in signatures related to T-cell biology, including CTLA-4 signalling. Similarly, in the TMA cohorts, non-Asian GCs showed significantly higher expression of T-cell markers (CD3, CD45R0, CD8) and lower expression of the immunosuppressive T-regulatory cell marker FOXP3 compared to Asian GCs (p<0.05). Inflammatory cell markers CD66b and CD68 also exhibited significant cohort differences (p<0.05). Exploratory analyses revealed a significant relationship between tumour immunity factors, geographic locality-specific prognosis, and postchemotherapy outcomes. Conclusions Analyses of >1600 GCs suggest that Asian and non-Asian GCs exhibit distinct tumour immunity signatures related to T-cell function. These differences may influence geographical differences in clinical outcome, and the design of future trials particularly in immuno-oncology. PMID:25385008

Research Resource: Preovulatory LH Surge Effects on Follicular Theca and Granulosa Transcriptomes

PubMed Central

Gunewardena, Sumedha; Hong, Xiaoman; Spitschak, Marion; Baufeld, Anja

2013-01-01

The molecular mechanisms that regulate the pivotal transformation processes observed in the follicular wall following the preovulatory LH surge, are still not established, particularly for cells of the thecal layer. To elucidate thecal cell (TC) and granulosa cell (GC) type-specific biologic functions and signaling pathways, large dominant bovine follicles were collected before and 21 hours after an exogenous GnRH-induced LH surge. Antral GCs (aGCs; aspirated by follicular puncture) and membrane-associated GCs (mGCs; scraped from the follicular wall) were compared with TC expression profiles determined by mRNA microarrays. Of the approximately 11 000 total genes expressed in the periovulatory follicle, only 2% of thecal vs 25% of the granulosa genes changed in response to the LH surge. The majority of the 203 LH-regulated thecal genes were also LH regulated in GCs, leaving a total of 57 genes as LH-regulated TC-specific genes. Of the 57 thecal-specific LH-regulated genes, 74% were down-regulated including CYP17A1 and NR5A1, whereas most other genes are being identified for the first time within theca. Many of the newly identified up-regulated thecal genes (eg, PTX3, RND3, PPP4R4) were also up-regulated in granulosa. Minimal expression differences were observed between aGCs and mGCs; however, transcripts encoding extracellular proteins (NID2) and matrix modulators (ADAMTS1, SASH1) dominated these differences. We also identified large numbers of unknown LH-regulated GC genes and discuss their putative roles in ovarian function. This Research Resource provides an easy-to-access global evaluation of LH regulation in TCs and GCs that implicates numerous molecular pathways heretofore unknown within the follicle. PMID:23716604

Research resource: preovulatory LH surge effects on follicular theca and granulosa transcriptomes.

PubMed

Christenson, Lane K; Gunewardena, Sumedha; Hong, Xiaoman; Spitschak, Marion; Baufeld, Anja; Vanselow, Jens

2013-07-01

The molecular mechanisms that regulate the pivotal transformation processes observed in the follicular wall following the preovulatory LH surge, are still not established, particularly for cells of the thecal layer. To elucidate thecal cell (TC) and granulosa cell (GC) type-specific biologic functions and signaling pathways, large dominant bovine follicles were collected before and 21 hours after an exogenous GnRH-induced LH surge. Antral GCs (aGCs; aspirated by follicular puncture) and membrane-associated GCs (mGCs; scraped from the follicular wall) were compared with TC expression profiles determined by mRNA microarrays. Of the approximately 11 000 total genes expressed in the periovulatory follicle, only 2% of thecal vs 25% of the granulosa genes changed in response to the LH surge. The majority of the 203 LH-regulated thecal genes were also LH regulated in GCs, leaving a total of 57 genes as LH-regulated TC-specific genes. Of the 57 thecal-specific LH-regulated genes, 74% were down-regulated including CYP17A1 and NR5A1, whereas most other genes are being identified for the first time within theca. Many of the newly identified up-regulated thecal genes (eg, PTX3, RND3, PPP4R4) were also up-regulated in granulosa. Minimal expression differences were observed between aGCs and mGCs; however, transcripts encoding extracellular proteins (NID2) and matrix modulators (ADAMTS1, SASH1) dominated these differences. We also identified large numbers of unknown LH-regulated GC genes and discuss their putative roles in ovarian function. This Research Resource provides an easy-to-access global evaluation of LH regulation in TCs and GCs that implicates numerous molecular pathways heretofore unknown within the follicle.

Simplifying the use of prognostic information in traumatic brain injury. Part 2: Graphical presentation of probabilities.

PubMed

Murray, Gordon D; Brennan, Paul M; Teasdale, Graham M

2018-06-01

OBJECTIVE Clinical features such as those included in the Glasgow Coma Scale (GCS) score, pupil reactivity, and patient age, as well as CT findings, have clear established relationships with patient outcomes due to neurotrauma. Nevertheless, predictions made from combining these features in probabilistic models have not found a role in clinical practice. In this study, the authors aimed to develop a method of displaying probabilities graphically that would be simple and easy to use, thus improving the usefulness of prognostic information in neurotrauma. This work builds on a companion paper describing the GCS-Pupils score (GCS-P) as a tool for assessing the clinical severity of neurotrauma. METHODS Information about early GCS score, pupil response, patient age, CT findings, late outcome according to the Glasgow Outcome Scale, and mortality were obtained at the individual adult patient level from the CRASH (Corticosteroid Randomisation After Significant Head Injury; n = 9045) and IMPACT (International Mission for Prognosis and Clinical Trials in TBI; n = 6855) databases. These data were combined into a pooled data set for the main analysis. Logistic regression was first used to model the combined association between the GCS-P and patient age and outcome, following which CT findings were added to the models. The proportion of variability in outcomes "explained" by each model was assessed using Nagelkerke's R 2 . RESULTS The authors observed that patient age and GCS-P have an additive effect on outcome. The probability of mortality 6 months after neurotrauma is greater with increasing age, and for all age groups the probability of death is greater with decreasing GCS-P. Conversely, the probability of favorable recovery becomes lower with increasing age and lessens with decreasing GCS-P. The effect of combining the GCS-P with patient age was substantially more informative than the GCS-P, age, GCS score, or pupil reactivity alone. Two-dimensional charts were produced displaying outcome probabilities, as percentages, for 5-year increments in age between 15 and 85 years, and for GCS-Ps ranging from 1 to 15; it is readily seen that the movement toward combinations at the top right of the charts reflects a decreasing likelihood of mortality and an increasing likelihood of favorable outcome. Analysis of CT findings showed that differences in outcome are very similar between patients with or without a hematoma, absent cisterns, or subarachnoid hemorrhage. Taken in combination, there is a gradation in risk that aligns with increasing numbers of any of these abnormalities. This information provides added value over age and GCS-P alone, supporting a simple extension of the earlier prognostic charts by stratifying the original charts in the following 3 CT groupings: none, only 1, and 2 or more CT abnormalities. CONCLUSIONS The important prognostic features in neurotrauma can be brought together to display graphically their combined effects on risks of death or on prospects for independent recovery. This approach can support decision making and improve communication of risk among health care professionals, patients, and their relatives. These charts will not replace clinical judgment, but they will reduce the risk of influences from biases.

Gradient cuts and extremal edges in relative depth and figure-ground perception.

PubMed

Ghose, Tandra; Palmer, Stephen E

2016-02-01

Extremal edges (EEs) are borders consisting of luminance gradients along the projected edge of a partly self-occluding curved surface (e.g., a cylinder), with equiluminant contours (ELCs) that run approximately parallel to that edge. Gradient cuts (GCs) are similar luminance gradients with ELCs that intersect (are "cut" by) an edge that could be due to occlusion. EEs are strongly biased toward being seen as closer/figural surfaces (Palmer & Ghose, Psychological Science, 19(1), 77-83, 2008). Do GCs produce a complementary bias toward being seen as ground? Experiment 1 shows that, with EEs on the opposite side, GCs produce a ground bias that increases with increasing ELC angles between ELCs and the shared edge. Experiment 2 shows that, with flat surfaces on the opposite side, GCs do not produce a ground bias, suggesting that more than one factor may be operating. We suggest that two partially dissociable factors may operate for curved surfaces-ELC angle and 3-D surface convexity-that reinforce each other in the figural cues of EEs but compete with each other in GCs. Moreover, this figural bias is modulated by the presence of EEs and GCs, as specified by the ELC angle between ELCs and the shared contour.

Acidity-triggered charge-convertible nanoparticles that can cause bacterium-specific aggregation in situ to enhance photothermal ablation of focal infection.

PubMed

Korupalli, Chiranjeevi; Huang, Chieh-Cheng; Lin, Wei-Chih; Pan, Wen-Yu; Lin, Po-Yen; Wan, Wei-Lin; Li, Meng-Ju; Chang, Yen; Sung, Hsing-Wen

2017-02-01

Focal infections that are caused by antibiotic-resistant bacteria are becoming an ever-growing challenge to human health. To address this challenge, a pH-responsive amphiphilic polymer of polyaniline-conjugated glycol chitosan (PANI-GCS) that can self-assemble into nanoparticles (NPs) in situ is developed. The PANI-GCS NPs undergo a unique surface charge conversion that is induced by their local pH, favoring bacterium-specific aggregation without direct contact with host cells. Following conjugation onto GCS, the optical-absorbance peak of PANI is red-shifted toward the near-infrared (NIR) region, enabling PANI-GCS NPs to generate a substantial amount of heat, which is emitted to their neighborhood. The local temperature of the NIR-irradiated PANI-GCS NPs is estimated to be approximately 5 °C higher than their ambient tissue temperature, ensuring specific and direct heating of their aggregated bacteria; hence, damage to tissue is reduced and wound healing is accelerated. The above results demonstrate that PANI-GCS NPs are practical for use in the photothermal ablation of focal infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

The relation between Glasgow Coma Scale score and later cerebral atrophy in paediatric traumatic brain injury.

PubMed

Ghosh, Alokananda; Wilde, Elisabeth A; Hunter, Jill V; Bigler, Erin D; Chu, Zili; Li, Xiaoqi; Vasquez, Ana C; Menefee, Deleene; Yallampalli, Ragini; Levin, Harvey S

2009-03-01

To examine initial Glasgow Coma Scale (GCS) score and its relationship with later cerebral atrophy in children with traumatic brain injury (TBI) using Quantitative Magnetic Resonance Imaging (QMRI) at 4 months post-injury. It was hypothesized that a lower GCS score would predict later generalized atrophy. As a guide in assessing paediatric TBI patients, the probability of developing chronic cerebral atrophy was determined based on the initial GCS score. The probability model used data from 45 paediatric patients (mean age = 13.6) with mild-to-severe TBI and 41 paediatric (mean age = 12.4) orthopaedically-injured children. This study found a 24% increase in the odds of developing an abnormal ventricle-to-brain ratio (VBR) and a 27% increase in the odds of developing reduced white matter percentage on neuroimaging with each numerical drop in GCS score. Logistic regression models with cut-offs determined by normative QMRI data confirmed that a lower initial GCS score predicts later atrophy. GCS is a commonly used measure of injury severity. It has proven to be a prognostic indicator of cognitive recovery and functional outcome and is also predictive of later parenchymal change.

Adverse eff ects of polymeric nanoparticle poly(ethylene glycol)- block-polylactide methyl ether (PEG-b-PLA) on steroid hormone secretion by porcine granulosa cells.

PubMed

Scsukova, Sona; Bujnakova, Mlynarcikova A; Kiss, A; Rollerova, E

2017-04-25

Development of nanoparticles (NPs) for biomedical applications, including medical imaging and drug delivery, is currently undergoing a dramatic expansion. Diverse effects of different type NPs relating to mammalian reproductive tissues have been demonstrated. Th e objective of this study was to explore the in vitro effects of polymeric nanoparticle poly(ethylene glycol)-blockpolylactide methyl ether (PEG-b-PLA NPs) on functional state and viability of ovarian granulosa cells (GCs), which play an important role in maintaining ovarian function and female fertility. The GCs isolated from porcine ovarian follicles were incubated with the different concentrations of PEG-b-PLA NPs (PEG average Mn=350 g/mol and PLA average Mn=1000 g/mol; 0.2-100 μg/ml) or poly(ethylene glycol) with an average molecular weight of 300 (PEG-300; 0.2- 40 mg/ml) in the presence or absence of stimulators, follicle-stimulating hormone (FSH; 1 μg/ml), androstenedione (100 nM), forskolin (10 μM) or 8Br-cAMP (100 μM), for different time periods (24, 48, 72 h). At the end of the incubation, progesterone and estradiol levels produced by GCs were measured in the culture media by radioimmunoassay. Th e viability of GCs was determined by the method using a colorimetric assay with MTT. Treatment of GCs with PEG-b-PLA NPs induced a significant decrease in basal as well as FSH-stimulated progesterone secretion above the concentration of 20 and 4 μg/ml, respectively. Moreover, PEG-b-PLA NPs reduced forskolin-stimulated, but not cAMP-stimulated progesterone production by GCs. A dose-dependent inhibition of androstenedione-stimulated estradiol release by GCs was found by the action of PEG-b-PLA NPs. Incubation of GCs with PEG-300 significantly inhibited basal as well as FSH-stimulated progesterone secretion above the concentration of 40 mg/ml. PEG-b-PLA NPs and PEG-300 significantly reduced the viability of GCs at the highest tested concentrations (100 μg/ml and 40 mg/ml, respectively). The obtained results indicate that polymeric NPs PEG-b-PLA might induce alterations in steroid hormone production by ovarian GCs and thereby could modify reproductive functions.

Associations of HSP90AA2 gene polymorphisms with disease susceptibility, glucocorticoids efficacy and health-related quality of life in Chinese systemic lupus erythematosus patients.

PubMed

Zhang, Man; Li, Su-Su; Xie, Qiao-Mei; Xu, Jian-Hua; Sun, Xiu-Xiu; Pan, Fa-Ming; Xu, Sheng-Qian; Liu, Sheng-Xiu; Tao, Jin-Hui; Liu, Shuang; Cai, Jing; Chen, Pei-Ling; Qian, Long; Wang, Chun-Huai; Liang, Chun-Mei; Huang, Hai-Liang; Pan, Hai-Feng; Su, Hong; Zou, Yan-Feng

2018-06-15

Although the current glucocorticoids (GCs) treatment for systemic lupus erythematosus (SLE) is effective to a certain extent, the difference in therapeutic effect between patients is still a widespread problem. Some patients can have repeated attacks that greatly diminish their quality of life. This study was conducted to investigate the relationship between HSP90AA2 polymorphisms and disease susceptibility, GCs efficacy and health-related quality of life (HRQoL) in Chinese SLE patients. A case-control study was performed in 470 SLE patients and 470 normal controls. Then, 444 patients in the case group were followed up for 12 weeks to observe efficacy of GCs and improvement of HRQoL. Two single nucleotide polymorphisms (SNPs) of HSP90AA2 were selected for genotyping: rs1826330 and rs6484340. HRQoL was assessed using the SF-36 questionnaire. The minor T allele of rs1826330 and the TT haplotype formed by rs1826330 and rs6484340 showed associations with decreased SLE risk (T allele: P BH  = 0.022; TT haplotype: P BH  = 0.033). A significant association between rs6484340 and improvement of HRQoL was revealed in the follow-up study. Five subscales of SF-36 were appeared to be influenced by rs6484340: total score of SF-36 (additive model: P BH  = 0.026), physical function (additive model: P BH  = 0.026), role-physical (recessive model: P BH  = 0.041), mental health (dominant model: P BH  = 0.047), and physical component summary (additive model: P BH  = 0.026). No statistical significance was found between HSP90AA2 gene polymorphisms and GCs efficacy. These results revealed a genetic association between HSP90AA2 and SLE. Remarkably, HSP90AA2 has an impact on the improvement of HRQoL in Chinese population with SLE.

Retrospective evaluation of prehospital triage, presentation, interventions and outcome in paediatric drowning managed by a physician staffed helicopter emergency medical service.

PubMed

Garner, Alan A; Barker, Claire L; Weatherall, Andrew D

2015-11-06

Drowning patients may benefit from the advanced airway management capabilities that can be provided by physician staffed helicopter emergency medical services. The aim of this study is to describe paediatric drowning patients treated by such a service examining tasking systems, initial physiology at the incident scene, survival and neurological outcome. Retrospective analysis of paediatric drowning victims over a 5- year period. Case identification system, patient age, site of drowning, presence or absence of cardiac output, first Glasgow Coma Scale (GCS) score and interventions were collected from prehospital notes, and survival and neurological outcomes from hospital and rehabilitation notes. The P-HEMS direct case identification system operating in parallel with a central control system identified all severe drowning cases but 3 of 7 cases (43%) were missed when the central control system operated in isolation. All severe drowning cases (22) identified for P-HEMS response were intubated and transported directly to a paediatric specialist centre. Intubation required adjuvant anaesthesia in 10 (45%) cases. All children with GCS greater than eight on arrival of the P-HEMS survived neurologically intact. Seven of eight children with a GCS between four and seven survived without neurological impairment and all children with a GCS greater than three survived. Four of twelve asystolic children survived including one child who at 18 months post drowning is neurologically normal. All children who survived had return of spontaneous circulation prior to arrival in the emergency department. P-HEMS played a significant role in the management of severe paediatric drowning in this case series. Requirement for P-HEMS only interventions were high and all identified cases were transferred directly to a paediatric specialist centre. Discontinuation of the P-HEMS direct case identication system that operated during the majority of the study period resulted in deterioration in system performance with some paediatric drowning cases subsequently not identified for P-HEMS response being transported to adult hospitals.

Instrument Display Visual Angles for Conventional Aircraft and the MQ-9 Ground Control Station

NASA Technical Reports Server (NTRS)

Bendrick, Gregg A.; Kamine, Tovy Haber

2008-01-01

Aircraft instrument panels should be designed such that primary displays are in optimal viewing location to minimize pilot perception and response time. Human Factors engineers define three zones (i.e. "cones") of visual location: 1) "Easy Eye Movement" (foveal vision); 2) "Maximum Eye Movement" (peripheral vision with saccades), and 3) "Head Movement" (head movement required). Instrument display visual angles were measured to determine how well conventional aircraft (T-34, T-38, F- 15B, F-16XL, F/A-18A, U-2D, ER-2, King Air, G-III, B-52H, DC-10, B747-SCA) and the MQ-9 ground control station (GCS) complied with these standards, and how they compared with each other. Methods: Selected instrument parameters included: attitude, pitch, bank, power, airspeed, altitude, vertical speed, heading, turn rate, slip/skid, AOA, flight path, latitude, longitude, course, bearing, range and time. Vertical and horizontal visual angles for each component were measured from the pilot s eye position in each system. Results: The vertical visual angles of displays in conventional aircraft lay within the cone of "Easy Eye Movement" for all but three of the parameters measured, and almost all of the horizontal visual angles fell within this range. All conventional vertical and horizontal visual angles lay within the cone of "Maximum Eye Movement". However, most instrument vertical visual angles of the MQ-9 GCS lay outside the cone of "Easy Eye Movement", though all were within the cone of "Maximum Eye Movement". All the horizontal visual angles for the MQ-9 GCS were within the cone of "Easy Eye Movement". Discussion: Most instrument displays in conventional aircraft lay within the cone of "Easy Eye Movement", though mission-critical instruments sometimes displaced less important instruments outside this area. Many of the MQ-9 GCS systems lay outside this area. Specific training for MQ-9 pilots may be needed to avoid increased response time and potential error during flight.

Somatic hypermutation and antigen-driven selection of B cells are altered in autoimmune diseases.

PubMed

Zuckerman, Neta S; Hazanov, Helena; Barak, Michal; Edelman, Hanna; Hess, Shira; Shcolnik, Hadas; Dunn-Walters, Deborah; Mehr, Ramit

2010-12-01

B cells have been found to play a critical role in the pathogenesis of several autoimmune (AI) diseases. A common feature amongst many AI diseases is the formation of ectopic germinal centers (GC) within the afflicted tissue or organ, in which activated B cells expand and undergo somatic hypermutation (SHM) and antigen-driven selection on their immunoglobulin variable region (IgV) genes. However, it is not yet clear whether these processes occurring in ectopic GCs are identical to those in normal GCs. The analysis of IgV mutations has aided in revealing many aspects concerning B cell expansion, mutation and selection in GC reactions. We have applied several mutation analysis methods, based on lineage tree construction, to a large set of data, containing IgV productive and non-productive heavy and light chain sequences from several different tissues, to examine three of the most profoundly studied AI diseases - Rheumatoid Arthritis (RA), Multiple Sclerosis (MS) and Sjögren's Syndrome (SS). We have found that RA and MS sequences exhibited normal mutation spectra and targeting motifs, but a stricter selection compared to normal controls, which was more apparent in RA. SS sequence analysis results deviated from normal controls in both mutation spectra and indications of selection, also showing differences between light and heavy chain IgV and between different tissues. The differences revealed between AI diseases and normal control mutation patterns may result from the different microenvironmental influences to which ectopic GCs are exposed, relative to those in normal secondary lymphoid tissues. Copyright © 2010 Elsevier Ltd. All rights reserved.

The epidemiology of asthma and its comorbidities in Poland--Health problems of patients with severe asthma as evidenced in the Province of Lodz.

PubMed

Panek, Michał; Mokros, Łukasz; Pietras, Tadeusz; Kuna, Piotr

2016-03-01

Population studies supply interesting data regarding the epidemiology, comorbidity and risk factors of asthma, which have direct clinical implications for patients. The aim of the work was to evaluate the degree of severity of asthma in the studied group, the levels of anti-asthma treatment, the prevalence of asthma comorbidities and their influence on the clinical course of the illness. The study encompassed 451 participants: 52.11% were asthma patients (study group) and 47.89% were healthy subjects (controls). Respiratory function tests, ACT™ test and skin prick tests were performed. Asthma severity was mild in 14.89%, moderate in 49.36% and severe in 35.74%. Oral GCS were used by 29%, inhalers 44%, LABA 68%, SABA 67%, LAMA 6%, SAMA 14% and MX 16%. Rhinitis and allergy were significantly more common in patients. GERD and neurological diseases were risk factors for asthma, and GERD significantly intensified the risk of severe asthma. GERD, atherosclerosis, hypertension, ischaemic heart disease and other cardiac diseases, lipid disorders, COPD, and the presence of any neoplastic disease significantly worsened the degree of asthma control. Severe asthma was a significant clinical issue in over 35% of cases. The most commonly-used group of drugs were LABAs, while inhaled GCS and LAMA were uncommon, especially among severe cases. A significant problem was the high percentage of systemic GCS used by severe cases. The most important risk factor for asthma, including its severe form, is GERD. Numerous comorbid conditions significantly worsen the degree of asthma control. Copyright © 2016 Elsevier Ltd. All rights reserved.

Formation of Globular Clusters with Internal Abundance Spreads in r-Process Elements: Strong Evidence for Prolonged Star Formation

NASA Astrophysics Data System (ADS)

Bekki, Kenji; Tsujimoto, Takuji

2017-07-01

Several globular clusters (GCs) in the Galaxy are observed to show internal abundance spreads in r-process elements (e.g., Eu). We propose a new scenario that explains the origin of these GCs (e.g., M5 and M15). In this scenario, stars with no/little abundance variations first form from a massive molecular cloud (MC). After all of the remaining gas of the MC is expelled by numerous supernovae, gas ejected from asymptotic giant branch stars can be accumulated in the central region of the GC to form a high-density intracluster medium (ICM). Merging of neutron stars then occurs to eject r-process elements, which can be efficiently trapped in and subsequently mixed with the ICM. New stars formed from the ICM can have r-process abundances that are quite different from those of earlier generations of stars within the GC. This scenario can explain both (I) why r-process elements can be trapped within GCs and (II) why GCs with internal abundance spreads in r-process elements do not show [Fe/H] spreads. Our model shows (I) that a large fraction of Eu-rich stars can be seen in Na-enhanced stellar populations of GCs, as observed in M15, and (II) why most of the Galactic GCs do not exhibit such internal abundance spreads. Our model demonstrates that the observed internal spreads of r-process elements in GCs provide strong evidence for prolonged star formation (˜108 yr).

An Automated Strategy for Unbiased Morphometric Analyses and Classifications of Growth Cones In Vitro

PubMed Central

Chitsaz, Daryan; Morales, Daniel; Law, Chris; Kania, Artur

2015-01-01

During neural circuit development, attractive or repulsive guidance cue molecules direct growth cones (GCs) to their targets by eliciting cytoskeletal remodeling, which is reflected in their morphology. The experimental power of in vitro neuronal cultures to assay this process and its molecular mechanisms is well established, however, a method to rapidly find and quantify multiple morphological aspects of GCs is lacking. To this end, we have developed a free, easy to use, and fully automated Fiji macro, Conographer, which accurately identifies and measures many morphological parameters of GCs in 2D explant culture images. These measurements are then subjected to principle component analysis and k-means clustering to mathematically classify the GCs as “collapsed” or “extended”. The morphological parameters measured for each GC are found to be significantly different between collapsed and extended GCs, and are sufficient to classify GCs as such with the same level of accuracy as human observers. Application of a known collapse-inducing ligand results in significant changes in all parameters, resulting in an increase in ‘collapsed’ GCs determined by k-means clustering, as expected. Our strategy provides a powerful tool for exploring the relationship between GC morphology and guidance cue signaling, which in particular will greatly facilitate high-throughput studies of the effects of drugs, gene silencing or overexpression, or any other experimental manipulation in the context of an in vitro axon guidance assay. PMID:26496644

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

Powalka, Mathieu; Lançon, Ariane; Duc, Pierre-Alain

Large samples of globular clusters (GC) with precise multi-wavelength photometry are becoming increasingly available and can be used to constrain the formation history of galaxies. We present the results of an analysis of Milky Way (MW) and Virgo core GCs based on 5 optical-near-infrared colors and 10 synthetic stellar population models. For the MW GCs, the models tend to agree on photometric ages and metallicities, with values similar to those obtained with previous studies. When used with Virgo core GCs, for which photometry is provided by the Next Generation Virgo cluster Survey (NGVS), the same models generically return younger ages.more » This is a consequence of the systematic differences observed between the locus occupied by Virgo core GCs and models in panchromatic color space. Only extreme fine-tuning of the adjustable parameters available to us can make the majority of the best-fit ages old. Although we cannot exclude that the formation history of the Virgo core may lead to more conspicuous populations of relatively young GCs than in other environments, we emphasize that the intrinsic properties of the Virgo GCs are likely to differ systematically from those assumed in the models. Thus, the large wavelength coverage and photometric quality of modern GC samples, such as those used here, is not by itself sufficient to better constrain the GC formation histories. Models matching the environment-dependent characteristics of GCs in multi-dimensional color space are needed to improve the situation.« less

Benzylic rearrangement stable isotope labeling for quantitation of guanidino and ureido compounds in thyroid tissues by liquid chromatography-electrospray ionization mass spectrometry.

PubMed

Fan, Ruo-Jing; Guan, Qing; Zhang, Fang; Leng, Jia-Peng; Sun, Tuan-Qi; Guo, Yin-Long

2016-02-18

Benzylic rearrangement stable isotope labeling (BRSIL) was explored to quantify the guanidino and ureido compounds (GCs and UCs). This method employed a common reagent, benzil, to label the guanidino and ureido groups through nucleophilic attacking then benzylic migrating. The use of BRSIL was investigated in the analysis of five GCs (creatine, l-arginine, homoarginine, 4-guanidinobutyric acid, and methylguanidine) and two UCs (urea and citrulline). The labeling was found simple and specific. The introduction of bi-phenyl group and the generation of nitrogen heterocyclic ring in the benzil-d0/d5 labeled GCs and UCs improved the retention behaviors in liquid chromatography (LC) and increased the sensitivity of electrospray ionization mass spectrometry (ESI MS) detection. The fragment ion pairs of m/z 182/187 and m/z 210/215 from the benzil-d0/d5 tags facilitated the discovery of potential GCs and UCs candidates residing in biological matrices. The use of BRSIL combined with LC-ESI MS was applied for simultaneously quantitation of GCs and UCs in thyroid tissues. It was demonstrated that nine GCs and UCs were detected, six of which were further quantified based on corresponding standards. It was concluded that five GCs and UCs (l-arginine, homoarginine, 4-guanidinobutyric acid, methylguanidine, and citrulline) were statistically significantly different (p < 0.05) between the para-carcinoma and carcinoma thyroid tissue samples. Copyright © 2016 Elsevier B.V. All rights reserved.

The value of eutherian-marsupial comparisons for understanding the function of glucocorticoids in female mammal reproduction.

PubMed

Fanson, Kerry V; Parrott, Marissa L

2015-11-01

This article is part of a Special Issue "SBN 2014". Chronic stress is known to inhibit female reproductive function. Consequently, it is often assumed that glucocorticoid (GC) concentrations should be negatively correlated with reproductive success because of the role they play in stress physiology. In contrast, a growing body of evidence indicates that GCs play an active role in promoting reproductive function. It is precisely because GCs are so integral to the entire process that disruptions to adrenal activity have negative consequences for reproduction. The goal of this paper is to draw attention to the increasing evidence showing that increases in adrenal activity are important for healthy female reproduction. Furthermore, we outline several hypotheses about the functional role(s) that GCs may play in mediating reproduction and argue that comparative studies between eutherian and marsupial mammals, which exhibit some pronounced differences in reproductive physiology, may be particularly useful for testing different hypotheses about the functional role of GCs in reproduction. Much of our current thinking about GCs and reproduction comes from research involving stress-induced levels of GCs and has led to broad assumptions about the effects of GCs on reproduction. Unfortunately, this has left a gaping hole in our knowledge about basal GC levels and how they may influence reproductive function, thereby preventing a broader understanding of adrenal physiology and obscuring potential solutions for reproductive dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

Roles of Nano- and Micro-Scale Subsurface Geochemical Reactions on Environmentally Sustainable Geologic Carbon Dioxide Sequestration

NASA Astrophysics Data System (ADS)

Hu, Yandi

Geologic CO2 sequestration (GCS) is a promising approach to reduce anthropogenic CO2 emissions into the atmosphere. At GCS sites, injected CO2 is kept in formation rock by an overlying low permeability caprock. During and after CO2 injection, geochemical reactions can affect the porosity, permeability, and pollutant transport in aquifers. Despite their importance, nano- and micro-scale subsurface geochemical reactions are far from well-understood. Clay mobilization has been reported to decrease aquifer permeability during water flooding, and clay minerals are abundant in caprock. Thus, we studied CO2-brine-clay interactions under varied conditions relevant to different GCS sites (at 35-95°C and under 35-120 atm CO2, in water, NaCl, MgCl2, or CaCl2 solutions). Biotite, Fe-bearing mica, was used as a model clay mineral. We observed numerous fibrous illite precipitates on mica after reaction for only 3 h, which had not been previously reported. A few hours later, the mica surface cracked and fibrous illite detached. The mobilization of fibrous illite can decrease the aquifer's permeability greatly and affect the safety and efficiency of GCS. Mechanisms related to ion exchange, mica swelling, and CO2 intercalation were explored. Oriented aggregation of illite nanoparticles forming the fibrous illite was directly observed, suggesting a new mechanism for fibrous illite formation. Interestingly, besides the pH effect, aqueous CO2 enhances mica cracking over N2. These findings can help to achieve safer subsurface operations. At GCS field sites, Fe concentration increased near the injection sites and originally adsorbed pollutants were released. As the brine flows, Fe re-precipitated because of pH increase. To better predict the fate and transport of aqueous pollutants, the nucleation and growth of Fe(III) (hydr)oxides were studied. New information about sizes and volumes of the Fe(III) (hydr)oxide nanoparticles precipitated in solution and on quartz, mica, and sapphire were provided using small angle X-ray scattering, in the presence of different ions (Al 3+, Cl-, NO3-, and SO 42-). Using complementary techniques, the controlling mechanisms related to surface charge, bond formation, and interfacial energies were explored. These new findings can help better predict pollutant transport in aquifers not only at GCS sites, but also in managed aquifer recharge and acid mine drainage sites.

SMAD4 feedback regulates the canonical TGF-β signaling pathway to control granulosa cell apoptosis.

PubMed

Du, Xing; Pan, Zengxiang; Li, Qiqi; Liu, Honglin; Li, Qifa

2018-02-02

Canonical TGF-β signals are transduced from the cell surface to the cytoplasm, and then translocated into the nucleus, a process that involves ligands (TGF-β1), receptors (TGFBR2/1), receptor-activated SMADs (SMAD2/3), and the common SMAD (SMAD4). Here we provide evidence that SMAD4, a core component of the canonical TGF-β signaling pathway, regulates the canonical TGF-β signaling pathway in porcine granulosa cells (GCs) through a feedback mechanism. Genome-wide analysis and qRT-PCR revealed that SMAD4 affected miRNA biogenesis in GCs. Interestingly, TGFBR2, the type II receptor of the canonical TGF-β signaling pathway, was downregulated in SMAD4-silenced GCs and found to be a common target of SMAD4-inhibited miRNAs. miR-425, the most significantly elevated miRNA in SMAD4-silenced GCs, mediated the SMAD4 feedback regulation of the TGF-β signaling pathway. This was accomplished through a direct interaction between the transcription factor SMAD4 and the miR-425 promoter, and a direct interaction between miR-425 and the TGFBR2 3'-UTR. Furthermore, miR-425 enhanced GC apoptosis by targeting TGFBR2 and the canonical TGF-β signaling pathway, which was rescued by SMAD4 and TGF-β1. Overall, our findings demonstrate that a positive feedback mechanism exists within the canonical TGF-β signaling pathway. This study also provides new insights into mechanism underlying the canonical TGF-β signaling pathway, which regulates GC function and follicular development.

Globular cluster formation with multiple stellar populations: self-enrichment in fractal massive molecular clouds

NASA Astrophysics Data System (ADS)

Bekki, Kenji

2017-08-01

Internal chemical abundance spreads are one of fundamental properties of globular clusters (GCs) in the Galaxy. In order to understand the origin of such abundance spreads, we numerically investigate GC formation from massive molecular clouds (MCs) with fractal structures using our new hydrodynamical simulations with star formation and feedback effects of core-collapse supernovae (SNe) and asymptotic giant branch (AGB) stars. We particularly investigate star formation from gas chemically contaminated by SNe and AGB stars ('self-enrichment') in forming GCs within MCs with different initial conditions and environments. The principal results are as follows. GCs with multiple generations of stars can be formed from merging of hierarchical star cluster complexes that are developed from high-density regions of fractal MCs. Feedback effects of SNe and AGB stars can control the formation efficiencies of stars formed from original gas of MCs and from gas ejected from AGB stars. The simulated GCs have strong radial gradients of helium abundances within the central 3 pc. The original MC masses need to be as large as 107 M⊙ for a canonical initial stellar mass function (IMF) so that the final masses of stars formed from AGB ejecta can be ˜105 M⊙. Since star formation from AGB ejecta is rather prolonged (˜108 yr), their formation can be strongly suppressed by SNe of the stars themselves. This result implies that the so-called mass budget problem is much more severe than ever thought in the self-enrichment scenario of GC formation and thus that IMF for the second generation of stars should be 'top-light'.

A novel strategy for development of glucocorticoids through non-genomic mechanism.

PubMed

Zhou, Jian; Li, Min; Sheng, Chun-Quan; Liu, Lei; Li, Zhen; Wang, Yan; Zhou, Jiang-Rui; Jing, Zai-Ping; Chen, Yi-Zhang; Jiang, Chun-Lei

2011-04-01

Glucocorticoids (GCs) are routinely believed to take effect through genomic mechanisms, which are also largely responsible for GCs' side effects. Beneficial non-genomic effects of GCs have been reported as being independent of the genomic pathway. Here, we synthesized a new type of GCs, which took effect mainly via non-genomic mechanisms. Hydrocortisone was conjugated with glycine, lysine and phenylalanine to get a bigger molecular structure, which could hardly go through the cell membrane. Evaluation of the anti-inflammatory efficacy showed that hydrocortisone-conjugated glycine (HG) and lysine could inhibit neutrophil degranulation within 15 min. HG could inhibit IgE-mediated histamine release from mast cells via a non-genomic pathway, and rapidly alleviate allergic reaction. Luciferase reporter assay showed that HG would not activate the glucocorticoid response element within 30 min, which verified the rapid effects independent of the genomic pathway. The work proposes a novel insight into the development of novel GCs, and provides new tools for experimental study on non-genomic mechanisms.

Effects of thinned young apple polyphenols on the quality of grass carp (Ctenopharyngodon idellus) surimi during cold storage.

PubMed

Sun, Lijun; Sun, Jiaojiao; Thavaraj, Pridhuvi; Yang, Xingbin; Guo, Yurong

2017-06-01

The aim of this study was to investigate the effects of young apple polyphenols (YAP) on the quality of grass cap surimi (GCS) during storage at 4°C. The addition of YAP into GCS was found to be effective in delaying lipid oxidation, soluble myofibrillar protein (SMP) degradation and changes of L ∗ , a ∗ and b ∗ values of GCS. Chlorogenic acid was screened to be the primary component showing preservative effects. YAP was shown to protect the functional properties of SMP during cold storage, retarding both the decrease in emulsifying activity and stability, and the increase in surface hydrophobicity of SMP. Additionally, the loss of gel strength and texture of GCS with YAP were significantly (P<0.05) lower than that of GCS without YAP during cold storage. Therefore, YAP may be developed as a natural antioxidant to maintain the quality and to extend the shelf life of freshwater fish surimi. Copyright © 2016 Elsevier Ltd. All rights reserved.

Security Verification of Secure MANET Routing Protocols

DTIC Science & Technology

2012-03-22

SECURITY VERIFICATION OF SECURE MANET ROUTING PROTOCOLS THESIS Matthew F. Steele, Captain, USAF AFIT/GCS/ ENG /12-03 DEPARTMENT OF THE AIR FORCE AIR...States AFIT/GCS/ ENG /12-03 SECURITY VERIFICATION OF SECURE MANET ROUTING PROTOCOLS THESIS Presented to the Faculty Department of Electrical and Computer...DISTRIBUTION UNLIMITED AFIT/GCS/ ENG /12-03 SECURITY VERIFICATION OF SECURE MANET ROUTING PROTOCOLS Matthew F. Steele, B.S.E.E. Captain, USAF

Central Rotations of Milky Way Globular Clusters

NASA Astrophysics Data System (ADS)

Fabricius, Maximilian H.; Noyola, Eva; Rukdee, Surangkhana; Saglia, Roberto P.; Bender, Ralf; Hopp, Ulrich; Thomas, Jens; Opitsch, Michael; Williams, Michael J.

2014-06-01

Most Milky Way globular clusters (GCs) exhibit measurable flattening, even if on a very low level. Both cluster rotation and tidal fields are thought to cause this flattening. Nevertheless, rotation has only been confirmed in a handful of GCs, based mostly on individual radial velocities at large radii. We are conducting a survey of the central kinematics of Galactic GCs using the new Integral Field Unit instrument VIRUS-W. We detect rotation in all 11 GCs that we have observed so far, rendering it likely that a large majority of the Milky Way GCs rotate. We use published catalogs of GCs to derive central ellipticities and position angles. We show that in all cases where the central ellipticity permits an accurate measurement of the position angle, those angles are in excellent agreement with the kinematic position angles that we derive from the VIRUS-W velocity fields. We find an unexpected tight correlation between central rotation and outer ellipticity, indicating that rotation drives flattening for the objects in our sample. We also find a tight correlation between central rotation and published values for the central velocity dispersion, most likely due to rotation impacting the old dispersion measurements. This Letter includes data taken at The McDonald Observatory of The University of Texas at Austin.

Quality assurance for patients with head injuries admitted to a regional trauma unit.

PubMed

Schwartz, M L; Sharkey, P W; Andersen, J A

1991-07-01

The efficacy of trauma systems in reducing preventable deaths has been established but the methods of auditing care are still evolving. Various "audit filters" to identify which patients' charts should be reviewed have been proposed. An analysis of all patients admitted to the Regional Trauma Unit (RTU) over a 19-month period was conducted. Of 729 patients, 135 were identified as having suffered a traumatic intracranial hemorrhage (TICH). On review, neither delay in transfer from the emergency room to the operating room nor increasing time from the incident to the operating room correlated with increasing mortality. In contrast to delay, the Glasgow Coma Scale (GCS) score on admission correlated well with outcome. The charts of patients with anomalous outcomes based on admission GCS score were reviewed, and two possibly preventable deaths were identified. There were 48 patients with TICH who had no operations but there were no deaths attributable to a missed operation. There were 76 patients for whom the GCS score at the referring hospital and the GCS score on admission to the RTU were available. Seven of 19 patients who worsened on transfer declined because of significant pulmonary injuries. Anomalous outcomes based on admission GCS score and declining GCS scores are recommended as quality assurance filters.

Atrial granular cells of the snail Achatina fulica release proteins into hemolymph after stimulation of the heart nerve.

PubMed

Shabelnikov, Sergej V; Bystrova, Olga A; Ivanov, Vadim A; Margulis, Boris A; Martynova, Marina

2009-10-01

The atrium of the gastropod mollusc Achatina fulica receives rich innervation and contains numerous granular cells (GCs). We studied the atrial innervation and discovered that axon profiles typical in appearance of peptidergic neurons form close unspecialized membrane contacts with GCs. Then, we investigated, at both morphological and biochemical levels, the effect of electrical stimulation of the heart nerve on GCs of Achatina heart perfused in situ. The ultrastructural study demonstrated changes in granule morphology consistent with secretion. These events included alteration of granule content, intracellular granule fusion and formation of complex degranulation channels, within which the granule matrix solubilized. It was shown that electrical stimulation resulted in a significant increase of the total protein concentration in the perfusate. Furthermore, SDS-PAGE analysis of the perfusate revealed three new proteins with molecular masses of 16, 22, and 57 kDa. Affinity-purified polyclonal antibodies against the 16 kDa protein were obtained; the whole-mount immunofluorescence technique revealed the presence of this protein in the granules of atrial GCs. In GCs of the stimulated atrium, a progressive loss of their granular content was observed. The results suggest that the central nervous system can modulate the secretory activity of the atrial GCs through non-synaptic pathways.

Movement of Genetic Counselors from Clinical to Non-clinical Positions: Identifying Driving Forces.

PubMed

Cohen, Stephanie A; Tucker, Megan E

2018-03-05

A previous study of genetic counselors (GCs) in the state of Indiana identified movement out of clinical positions within the past 2 years. The aims of this study were to determine if this trend is nationwide and identify reasons why GCs are leaving their positions and factors that might help employers attract and retain GCs. An email was sent to members of the American Board of Genetic Counseling with a link to an online confidential survey. There were 939 responses (23.5% response rate). Overall, 52% of GCs report being highly satisfied in their current position, although almost two thirds think about leaving and one third had changed jobs within the past 2 years. Of those who had changed jobs (n = 295), 74.9% had been working in a hospital/clinic setting but only 46.3% currently do, demonstrating a major shift out of the clinic (p < 0.001). The top three reasons cited for leaving a position were work environment/institutional climate, salary/benefits, and a lack of feeling valued/recognized as a professional. These results confirm that GCs are moving out of clinical positions and document elements of job satisfaction. We suggest points for employers to consider when trying to recruit or retain GCs.

Retrograde transport from the yeast Golgi is mediated by two ARF GAP proteins with overlapping function.

PubMed Central

Poon, P P; Cassel, D; Spang, A; Rotman, M; Pick, E; Singer, R A; Johnston, G C

1999-01-01

ARF proteins, which mediate vesicular transport, have little or no intrinsic GTPase activity. They rely on the actions of GTPase-activating proteins (GAPs) for their function. The in vitro GTPase activity of the Saccharomyces cerevisiae ARF proteins Arf1 and Arf2 is stimulated by the yeast Gcs1 protein, and in vivo genetic interactions between arf and gcs1 mutations implicate Gcs1 in vesicular transport. However, the Gcs1 protein is dispensable, indicating that additional ARF GAP proteins exist. We show that the structurally related protein Glo3, which is also dispensable, also exhibits ARF GAP activity. Genetic and in vitro approaches reveal that Glo3 and Gcs1 have an overlapping essential function at the endoplasmic reticulum (ER)-Golgi stage of vesicular transport. Mutant cells deficient for both ARF GAPs cannot proliferate, undergo a dramatic accumulation of ER and are defective for protein transport between ER and Golgi. The glo3Delta and gcs1Delta single mutations each interact with a sec21 mutation that affects a component of COPI, which mediates vesicular transport within the ER-Golgi shuttle, while increased dosage of the BET1, BOS1 and SEC22 genes encoding members of a v-SNARE family that functions within the ER-Golgi alleviates the effects of a glo3Delta mutation. An in vitro assay indicates that efficient retrieval from the Golgi to the ER requires these two proteins. These findings suggest that Glo3 and Gcs1 ARF GAPs mediate retrograde vesicular transport from the Golgi to the ER. PMID:9927415

Formation of Globular Clusters with Internal Abundance Spreads in r -Process Elements: Strong Evidence for Prolonged Star Formation

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

Bekki, Kenji; Tsujimoto, Takuji

Several globular clusters (GCs) in the Galaxy are observed to show internal abundance spreads in r -process elements (e.g., Eu). We propose a new scenario that explains the origin of these GCs (e.g., M5 and M15). In this scenario, stars with no/little abundance variations first form from a massive molecular cloud (MC). After all of the remaining gas of the MC is expelled by numerous supernovae, gas ejected from asymptotic giant branch stars can be accumulated in the central region of the GC to form a high-density intracluster medium (ICM). Merging of neutron stars then occurs to eject r -processmore » elements, which can be efficiently trapped in and subsequently mixed with the ICM. New stars formed from the ICM can have r -process abundances that are quite different from those of earlier generations of stars within the GC. This scenario can explain both (i) why r -process elements can be trapped within GCs and (ii) why GCs with internal abundance spreads in r -process elements do not show [Fe/H] spreads. Our model shows (i) that a large fraction of Eu-rich stars can be seen in Na-enhanced stellar populations of GCs, as observed in M15, and (ii) why most of the Galactic GCs do not exhibit such internal abundance spreads. Our model demonstrates that the observed internal spreads of r -process elements in GCs provide strong evidence for prolonged star formation (∼10{sup 8} yr).« less

Differential release and phagocytosis of tegument glycoconjugates in neurocysticercosis: implications for immune evasion strategies.

PubMed

Alvarez, Jorge I; Rivera, Jennifer; Teale, Judy M

2008-04-09

Neurocysticercosis (NCC) is an infection of the central nervous system (CNS) by the metacestode of the helminth Taenia solium. The severity of the symptoms is associated with the intensity of the immune response. First, there is a long asymptomatic period where host immunity seems incapable of resolving the infection, followed by a chronic hypersensitivity reaction. Since little is known about the initial response to this infection, a murine model using the cestode Mesocestoides corti (syn. Mesocestoides vogae) was employed to analyze morphological changes in the parasite early in the infection. It was found that M. corti material is released from the tegument making close contact with the nervous tissue. These results were confirmed by infecting murine CNS with ex vivo-labeled parasites. Because more than 95% of NCC patients exhibit humoral responses against carbohydrate-based antigens, and the tegument is known to be rich in glycoconjugates (GCs), the expression of these types of molecules was analyzed in human, porcine, and murine NCC specimens. To determine the GCs present in the tegument, fluorochrome-labeled hydrazides as well as fluorochrome-labeled lectins with specificity to different carbohydrates were used. All the lectins utilized labeled the tegument. GCs bound by isolectinB4 were shed in the first days of infection and not resynthesized by the parasite, whereas GCs bound by wheat germ agglutinin and concavalinA were continuously released throughout the infectious process. GCs bound by these three lectins were taken up by host cells. Peanut lectin-binding GCs, in contrast, remained on the parasite and were not detected in host cells. The parasitic origin of the lectin-binding GCs found in host cells was confirmed using antibodies against T. solium and M. corti. We propose that both the rapid and persistent release of tegumental GCs plays a key role in the well-known immunomodulatory effects of helminths, including immune evasion and life-long inflammatory sequelae seen in many NCC patients.

Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas.

PubMed

Lin, Suling J; Gagnon-Bartsch, Johann A; Tan, Iain Beehuat; Earle, Sophie; Ruff, Louise; Pettinger, Katherine; Ylstra, Bauke; van Grieken, Nicole; Rha, Sun Young; Chung, Hyun Cheol; Lee, Ju-Seog; Cheong, Jae Ho; Noh, Sung Hoon; Aoyama, Toru; Miyagi, Yohei; Tsuburaya, Akira; Yoshikawa, Takaki; Ajani, Jaffer A; Boussioutas, Alex; Yeoh, Khay Guan; Yong, Wei Peng; So, Jimmy; Lee, Jeeyun; Kang, Won Ki; Kim, Sung; Kameda, Yoichi; Arai, Tomio; Zur Hausen, Axel; Speed, Terence P; Grabsch, Heike I; Tan, Patrick

2015-11-01

Differences in gastric cancer (GC) clinical outcomes between patients in Asian and non-Asian countries has been historically attributed to variability in clinical management. However, recent international Phase III trials suggest that even with standardised treatments, GC outcomes differ by geography. Here, we investigated gene expression differences between Asian and non-Asian GCs, and if these molecular differences might influence clinical outcome. We compared gene expression profiles of 1016 GCs from six Asian and three non-Asian GC cohorts, using a two-stage meta-analysis design and a novel biostatistical method (RUV-4) to adjust for technical variation between cohorts. We further validated our findings by computerised immunohistochemical analysis on two independent tissue microarray (TMA) cohorts from Asian and non-Asian localities (n=665). Gene signatures differentially expressed between Asians and non-Asian GCs were related to immune function and inflammation. Non-Asian GCs were significantly enriched in signatures related to T-cell biology, including CTLA-4 signalling. Similarly, in the TMA cohorts, non-Asian GCs showed significantly higher expression of T-cell markers (CD3, CD45R0, CD8) and lower expression of the immunosuppressive T-regulatory cell marker FOXP3 compared to Asian GCs (p<0.05). Inflammatory cell markers CD66b and CD68 also exhibited significant cohort differences (p<0.05). Exploratory analyses revealed a significant relationship between tumour immunity factors, geographic locality-specific prognosis, and postchemotherapy outcomes. Analyses of >1600 GCs suggest that Asian and non-Asian GCs exhibit distinct tumour immunity signatures related to T-cell function. These differences may influence geographical differences in clinical outcome, and the design of future trials particularly in immuno-oncology. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

T cell-replacing factor for glucocorticosteroid-induced immunoglobulin production. A unique steroid-dependent cytokine

PubMed Central

1983-01-01

Glucocorticosteroids (GCS) added to otherwise unstimulated cultures of human peripheral blood mononuclear cells (PBMC) induce the synthesis and secretion of all classes of immunoglobulin. The magnitude of this response is similar to that seen with other polyclonal B cell activators such as pokeweed mitogen (PWM), and like that of PWM, the steroid effect is dependent on both T cells and monocytes. To determine the cellular target for GCS in these cultures, separated populations of T cells and non-T cells were preincubated with steroids and then recombined. No immunoglobulin was produced in any of these preincubation experiments. As a different approach to this question, supernatants were collected from various cell populations following stimulation with PWM, concanavalin A (Con A), phytohemagglutinin (PHA), alloantigens, or GCS. These supernatants were tested for their effects on GCS-induced Ig production by B cells. Supernatants from 3-d cultures of unstimulated, as well as GCS-treated, PBMC contained a T cell- replacing factor that permitted T-depleted PBMC to produce Ig upon steroid stimulation. This supernatant factor (TRF-S) could be produced in the absence of steroid stimulation, but both the factor and GCS were necessary for the induction of Ig synthesis. Production of the TRF-S required the presence of both T cells and adherent cells in culture and was found in the highest concentrations at 3-4 d of culture. Supernatants from cultures stimulated with PWM, PHA, Con A, and alloantigens did not contain detectable TRF-S activity, and TRF-S was unable to replace helper T cells for PWM-induced Ig production. TRF-S required the presence of adherent cells in the T cell-depleted responder population for its action. Further, it was effective in inducing Ig production along with GCS in the presence of a sufficient concentration of cyclosporin A to block all T cell helper activity for primary responses of PBMC to PWM or GCS. TRF-S was inactivated by trypsin treatment, heating to 56 degrees C, freezing, lyophilization, and storage at 4 degrees C for greater than 3 wk. Its molecular weight is probably 10,000 daltons or more, since TRF-S activity is not rapidly dialyzable. These experiments indicate that GCS-induced Ig production by human B cells does not require the presence of intact T cells in the cultures and therefore the steroids are not exerting their influence directly on T suppressor or T helper cells. Furthermore, they demonstrate a previously unrecognized cytokine that induces the differentiation of human B cells to Ig production in the presence of GCS. PMID:6605406

VizieR Online Data Catalog: Carbon in red giants in GCs and dSph galaxies (Kirby+, 2015)

NASA Astrophysics Data System (ADS)

Kirby, E. N.; Guo, M.; Zhang, A. J.; Deng, M.; Cohen, J. G.; Guhathakurta, P.; Shetrone, M. D.; Lee, Y. S.; Rizzi, L.

2015-07-01

We obtained Keck/DEIMOS spectra of the carbon G band in red giants in Milky Way (MW) globular clusters (GCs) and dwarf spheroidal galaxies (dSphs) between 2011 Jul 29 and 2012 Mar 19. The GCs are NGC 2419, NGC 4590 (M68), and NGC 7078 (M15). The dSphs are Sculptor, Fornax, Ursa Minor, and Draco. See table 1. (3 data files).

Cellular protein quality control and the evolution of aggregates in spinocerebellar ataxia type 3 (SCA3).

PubMed

Seidel, K; Meister, M; Dugbartey, G J; Zijlstra, M P; Vinet, J; Brunt, E R P; van Leeuwen, F W; Rüb, U; Kampinga, H H; den Dunnen, W F A

2012-10-01

A characteristic of polyglutamine diseases is the increased propensity of disease proteins to aggregate, which is thought to be a major contributing factor to the underlying neurodegeneration. Healthy cells contain mechanisms for handling protein damage, the protein quality control, which must be impaired or inefficient to permit proteotoxicity under pathological conditions. We used a quantitative analysis of immunohistochemistry of the pons of eight patients with the polyglutamine disorder spinocerebellar ataxia type 3. We employed the anti-polyglutamine antibody 1C2, antibodies against p62 that is involved in delivering ubiquitinated protein aggregates to autophagosomes, antibodies against the chaperones HSPA1A and DNAJB1 and the proteasomal stress marker UBB⁺¹. The 1C2 antibody stained neuronal nuclear inclusions (NNIs), diffuse nuclear staining (DNS), granular cytoplasmic staining (GCS) and combinations, with reproducible distribution. P62 always co-localized with 1C2 in NNI. DNS and GCS co-stained with a lower frequency. UBB⁺¹ was present in a subset of neurones with NNI. A subset of UBB⁺¹-containing neurones displayed increased levels of HSPA1A, while DNAJB1 was sequestered into the NNI. Based on our results, we propose a model for the aggregation-associated pathology of spinocerebellar ataxia type 3: GCS and DNS aggregation likely represents early stages of pathology, which progresses towards formation of p62-positive NNI. A fraction of NNI exhibits UBB⁺¹ staining, implying proteasomal overload at a later stage. Subsequently, the stress-inducible HSPA1A is elevated while DNAJB1 is recruited into NNIs. This indicates that the stress response is only induced late when all endogenous protein quality control systems have failed. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

A Natural Interaction Interface for UAVs Using Intuitive Gesture Recognition

NASA Technical Reports Server (NTRS)

Chandarana, Meghan; Trujillo, Anna; Shimada, Kenji; Allen, Danette

2016-01-01

The popularity of unmanned aerial vehicles (UAVs) is increasing as technological advancements boost their favorability for a broad range of applications. One application is science data collection. In fields like Earth and atmospheric science, researchers are seeking to use UAVs to augment their current portfolio of platforms and increase their accessibility to geographic areas of interest. By increasing the number of data collection platforms UAVs will significantly improve system robustness and allow for more sophisticated studies. Scientists would like be able to deploy an available fleet of UAVs to fly a desired flight path and collect sensor data without needing to understand the complex low-level controls required to describe and coordinate such a mission. A natural interaction interface for a Ground Control System (GCS) using gesture recognition is developed to allow non-expert users (e.g., scientists) to define a complex flight path for a UAV using intuitive hand gesture inputs from the constructed gesture library. The GCS calculates the combined trajectory on-line, verifies the trajectory with the user, and sends it to the UAV controller to be flown.

Using Blue Stragglers to Predict Retained Black Hole Population in Globular Clusters

NASA Astrophysics Data System (ADS)

Hermanek, Keith; Chatterjee, Sourav; Rasio, Frederic

2018-01-01

Large numbers of black holes (BHs) are expected to form in massive star clusters typical of the globular clusters (GCs). Sophisticated theoretical models suggest that many of these BHs can be retained in present-day GCs. Observations have also identified several BH candidates in Galactic and extragalactic GCs (e.g., Macarone et al. 2007; Irwin et al. 2010; Strader et al. 2012; Chomiuk et al. 2013; Miller-Jones et al. 2014). It has also been shown that high-mass and high-density clusters such as GCs are efficient factories of merging binary BHs similar to those observed by the LIGO observatories (Abbott et al. 2016a,b,c,d,e; Rodriguez et al. 2016). Understanding the formation rate and properties of binary BHs are dependent on a detailed understanding of how the BHs dynamically evolve within GCs. Nevertheless, directly detecting BHs in GCs is extremely challenging; BHs only in binaries with limited configurations can be directly detected by the detection of gravitational wave, X-ray, or radio emissions. We propose an indirect of inferring the number of undetected retained BHs in a GC by investigating the dynamical effects of a large number of BHs on the production of other tracer populations such as Blue Straggler Stars (BSS). Using a large grid of detailed GC models we show that there is a clear anti-correlation between the number of BSS in a cluster and the number of retained BHs. Being the most massive species, large numbers of retained BHs will dominate the core of the cluster as a result of mass-segregation driving away other low-mass species such as main-sequence stars from central high-density regions. BSS are expected to form from physical collisions between main-sequence (MS) stars mediated by binary encounters (e.g., Chatterjee et al. 2013) in cores of GCs. Production of BSS by collisions or mass transfer channels are suppressed if a large number of retained BHs in a cluster restrict the number of MS stars in the core. Extensive observational data exist on the number and radial distribution of BSS in GCs. Thus, this anti-correlation between the number of retained BHs and the number of BSS, once carefully calibrated by theoretical models, can be used to infer the population of undetected BHs in GCs.

A comparison of the Full Outline of UnResponsiveness (FOUR) score and Glasgow Coma Score (GCS) in predictive modelling in traumatic brain injury.

PubMed

Kasprowicz, Magdalena; Burzynska, Malgorzata; Melcer, Tomasz; Kübler, Andrzej

2016-01-01

To compare the performance of multivariate predictive models incorporating either the Full Outline of UnResponsiveness (FOUR) score or Glasgow Coma Score (GCS) in order to test whether substituting GCS with the FOUR score in predictive models for outcome in patients after TBI is beneficial. A total of 162 TBI patients were prospectively enrolled in the study. Stepwise logistic regression analysis was conducted to compare the prediction of (1) in-ICU mortality and (2) unfavourable outcome at 3 months post-injury using as predictors either the FOUR score or GCS along with other factors that may affect patient outcome. The areas under the ROC curves (AUCs) were used to compare the discriminant ability and predictive power of the models. The internal validation was performed with bootstrap technique and expressed as accuracy rate (AcR). The FOUR score, age, the CT Rotterdam score, systolic ABP and being placed on ventilator within day one (model 1: AUC: 0.906 ± 0.024; AcR: 80.3 ± 4.8%) performed equally well in predicting in-ICU mortality as the combination of GCS with the same set of predictors plus pupil reactivity (model 2: AUC: 0.913 ± 0.022; AcR: 81.1 ± 4.8%). The CT Rotterdam score, age and either the FOUR score (model 3) or GCS (model 4) equally well predicted unfavourable outcome at 3 months post-injury (AUC: 0.852 ± 0.037 vs. 0.866 ± 0.034; AcR: 72.3 ± 6.6% vs. 71.9%±6.6%, respectively). Adding the FOUR score or GCS at discharge from ICU to predictive models for unfavourable outcome increased significantly their performances (AUC: 0.895 ± 0.029, p = 0.05; AcR: 76.1 ± 6.5%; p < 0.004 when compared with model 3; and AUC: 0.918 ± 0.025, p < 0.05; AcR: 79.6 ± 7.2%, p < 0.009 when compared with model 4), but there was no benefit from substituting GCS with the FOUR score. Results showed that FOUR score and GCS perform equally well in multivariate predictive modelling in TBI.

Comparison of Intra-cluster and M87 Halo Orphan Globular Clusters in the Virgo Cluster

NASA Astrophysics Data System (ADS)

Louie, Tiffany Kaye; Tuan, Jin Zong; Martellini, Adhara; Guhathakurta, Puragra; Toloba, Elisa; Peng, Eric; Longobardi, Alessia; Lim, Sungsoon

2018-01-01

We present a study of “orphan” globular clusters (GCs) — GCs with no identifiable nearby host galaxy — discovered in NGVS, a 104 deg2 CFHT/MegaCam imaging survey. At the distance of the Virgo cluster, GCs are bright enough to make good spectroscopic targets and many are barely resolved in good ground-based seeing. Our orphan GC sample is derived from a subset of NGVS-selected GC candidates that were followed up with Keck/DEIMOS spectroscopy. While our primary spectroscopic targets were candidate GC satellites of Virgo dwarf elliptical and ultra-diffuse galaxies, many objects turned out to be non-satellites based on a radial velocity mismatch with the Virgo galaxy they are projected close to. Using a combination of spectral characteristics (e.g., absorption vs. emission), Gaussian mixture modeling of radial velocity and positions, and extreme deconvolution analysis of ugrizk photometry and image morphology, these non-satellites were classified into: (1) intra-cluster GCs (ICGCs) in the Virgo cluster, (2) GCs in the outer halo of M87, (3) foreground Milky Way stars, and (4) background galaxies. The statistical distinction between ICGCs and M87 halo GCs is based on velocity distributions (mean of 1100 vs. 1300 km/s and dispersions of 700 vs. 400 km/s, respectively) and radial distribution (diffuse vs. centrally concentrated, respectively). We used coaddition to increase the spectral SNR for the two classes of orphan GCs and measured the equivalent widths (EWs) of the Mg b and H-beta absorption lines. These EWs were compared to single stellar population models to obtain mean age and metallicity estimates. The ICGCs and M87 halo GCs have <[Fe/H> = –0.6+/–0.3 and –0.4+/–0.3 dex, respectively, and mean ages of >~ 5 and >~ 10 Gyr, respectively. This suggests the M87 halo GCs formed in relatively high-mass galaxies that avoided being tidally disrupted by M87 until they were close to the cluster center, while IGCCs formed in relatively low-mass galaxies that were tidally disrupted in the cluster outskirts. Most of this work was carried out by high school students working under the auspices of the Science Internship Program (SIP) at UC Santa Cruz. We are grateful for financial support from the NSF and NASA/STScI.

The fate of radiation induced giant-nucleated cells of human skin fibroblasts

NASA Astrophysics Data System (ADS)

Almahwasi, A. A.; Jeynes, J. C.; Bradley, D. A.; Regan, P. H.

2017-11-01

Radiation-induced giant-nucleated cells (GCs) have been observed to occur within survivors of irradiated cancerous and within healthy cells, both in vivo and in vitro. The expression of such morphological alterations is associated with genomic instability. This study was designed to investigate the fate of GCs induced in a normal human fibroblast cell line (AG1522) after exposure to 0.2, 1 or 2 Gy of X-ray or proton irradiation. The total of 79 individual AG1522 GCs present at 7, 14 or 21 days after each dose point were analysed from fluorescence microscopy images captured over approximately 120 h. The GCs were identified at the beginning of the observation period for each time point post-irradiation and the area of the cell nucleus was measured (μm2) using a cell-recognition MATLAB code. The results demonstrate that the majority of GCs had undergone a prolonged mitotic arrest, which might be an indication of the survival strategy. The live cell microscopy confirms that a giant-nucleated cell formed 14 days after exposure to 0.2 Gy of proton irradiation was divided into two asymmetrical normal-sized cells. These results suggest that a small fraction of GCs can proliferate and form progeny. Some of GCs had disappeared from the microscopy fields. The rate of their loss was decreased as the dose increased but there remains the potential for them to have progeny that could continue to proliferate, ultimately contributing to development of cancer risk. This important method to access delayed effects in normal tissues could act as a potential radioprotective assay for a dose-limiting parameter when applying radiotherapy. These results might have important implications in evaluating risk estimates for patients during radiation therapy treatment.

The Hubble Space Telescope UV Legacy Survey of Galactic Globular Clusters - XII. The RGB bumps of multiple stellar populations

NASA Astrophysics Data System (ADS)

Lagioia, E. P.; Milone, A. P.; Marino, A. F.; Cassisi, S.; Aparicio, A. J.; Piotto, G.; Anderson, J.; Barbuy, B.; Bedin, L. R.; Bellini, A.; Brown, T.; D'Antona, F.; Nardiello, D.; Ortolani, S.; Pietrinferni, A.; Renzini, A.; Salaris, M.; Sarajedini, A.; van der Marel, R.; Vesperini, E.

2018-04-01

The Hubble Space Telescope UV Legacy Survey of Galactic Globular Clusters is providing a major breakthrough in our knowledge of globular clusters (GCs) and their stellar populations. Among the main results, we discovered that all the studied GCs host two main discrete groups consisting of first generation (1G) and second generation (2G) stars. We exploit the multiwavelength photometry from this project to investigate, for the first time, the Red Giant Branch Bump (RGBB) of the two generations in a large sample of GCs. We identified, with high statistical significance, the RGBB of 1G and 2G stars in 26 GCs and found that their magnitude separation as a function of the filter wavelength follows comparable trends. The comparison of observations to synthetic spectra reveals that the RGBB luminosity depends on the stellar chemical composition and that the 2G RGBB is consistent with stars enhanced in He and N and depleted in C and O with respect to 1G stars. For metal-poor GCs the 1G and 2G RGBB relative luminosity in optical bands mostly depends on helium content, Y. We used the RGBB observations in F606W and F814W bands to infer the relative helium abundance of 1G and 2G stars in 18 GCs, finding an average helium enhancement ΔY = 0.011 ± 0.002 of 2G stars with respect to 1G stars. This is the first determination of the average difference in helium abundance of multiple populations in a large number of clusters and provides a lower limit to the maximum internal variation of helium in GCs.

Autocrine action of BDNF on dendrite development of adult-born hippocampal neurons.

PubMed

Wang, Liang; Chang, Xingya; She, Liang; Xu, Duo; Huang, Wei; Poo, Mu-ming

2015-06-03

Dendrite development of newborn granule cells (GCs) in the dentate gyrus of adult hippocampus is critical for their incorporation into existing hippocampal circuits, but the cellular mechanisms regulating their dendrite development remains largely unclear. In this study, we examined the function of brain-derived neurotrophic factor (BDNF), which is expressed in adult-born GCs, in regulating their dendrite morphogenesis. Using retrovirus-mediated gene transfection, we found that deletion and overexpression of BDNF in adult-born GCs resulted in the reduction and elevation of dendrite growth, respectively. This effect was mainly due to the autocrine rather than paracrine action of BDNF, because deletion of BDNF only in the newborn GCs resulted in dendrite abnormality of these neurons to a similar extent as that observed in conditional knockout (cKO) mice with BDNF deleted in the entire forebrain. Furthermore, selective expression of BDNF in adult-born GCs in BDNF cKO mice fully restored normal dendrite development. The BDNF autocrine action was also required for the development of normal density of spines and normal percentage of spines containing the postsynaptic marker PSD-95, suggesting autocrine BDNF regulation of synaptogenesis. Furthermore, increased dendrite growth of adult-born GCs caused by voluntary exercise was abolished by BDNF deletion specifically in these neurons and elevated dendrite growth due to BDNF overexpression in these neurons was prevented by reducing neuronal activity with coexpression of inward rectifier potassium channels, consistent with activity-dependent autocrine BDNF secretion. Therefore, BDNF expressed in adult-born GCs plays a critical role in dendrite development by acting as an autocrine factor. Copyright © 2015 the authors 0270-6474/15/358384-10$15.00/0.

Student Modeling in an Intelligent Tutoring System

DTIC Science & Technology

1996-12-17

Multi-Agent Architecture." Advances in Artificial Intelligence : Proceedings of the 12 th Brazilian Symposium on Aritificial Intelligence , edited by...STUDENT MODELING IN AN INTELLIGENT TUTORING SYSTEM THESIS Jeremy E. Thompson Captain, USAF AFIT/GCS/ENG/96D-27 DIMTVMON* fCKAJWINT A Appr"v*d t=i...Air Force Base, Ohio AFIT/GCS/ENG/96D-27 STUDENT MODELING IN AN INTELLIGENT TUTORING SYSTEM THESIS Jeremy E. Thompson Captain, USAF AFIT/GCS/ENG/96D

Dysregulated Arl1, a regulator of post-Golgi vesicle tethering, can inhibit endosomal transport and cell proliferation in yeast

PubMed Central

Benjamin, Jeremy J. R.; Poon, Pak P.; Drysdale, John D.; Wang, Xiangmin; Singer, Richard A.; Johnston, Gerald C.

2011-01-01

Small monomeric G proteins regulated in part by GTPase-activating proteins (GAPs) are molecular switches for several aspects of vesicular transport. The yeast Gcs1 protein is a dual-specificity GAP for ADP-ribosylation factor (Arf) and Arf-like (Arl)1 G proteins, and also has GAP-independent activities. The absence of Gcs1 imposes cold sensitivity for growth and endosomal transport; here we present evidence that dysregulated Arl1 may cause these impairments. We show that gene deletions affecting the Arl1 or Ypt6 vesicle-tethering pathways prevent Arl1 activation and membrane localization, and restore growth and trafficking in the absence of Gcs1. A mutant version of Gcs1 deficient for both ArfGAP and Arl1GAP activity in vitro still allows growth and endosomal transport, suggesting that the function of Gcs1 that is required for these processes is independent of GAP activity. We propose that, in the absence of this GAP-independent regulation by Gcs1, the resulting dysregulated Arl1 prevents growth and impairs endosomal transport at low temperatures. In cells with dysregulated Arl1, an increased abundance of the Arl1 effector Imh1 restores growth and trafficking, and does so through Arl1 binding. Protein sequestration at the trans-Golgi membrane by dysregulated, active Arl1 may therefore be the mechanism of inhibition. PMID:21562219

The Next Generation Virgo Cluster Survey (NGVS). XXV. Fiducial Panchromatic Colors of Virgo Core Globular Clusters and Their Comparison to Model Predictions

NASA Astrophysics Data System (ADS)

Powalka, Mathieu; Lançon, Ariane; Puzia, Thomas H.; Peng, Eric W.; Liu, Chengze; Muñoz, Roberto P.; Blakeslee, John P.; Côté, Patrick; Ferrarese, Laura; Roediger, Joel; Sánchez-Janssen, Rúben; Zhang, Hongxin; Durrell, Patrick R.; Cuillandre, Jean-Charles; Duc, Pierre-Alain; Guhathakurta, Puragra; Gwyn, S. D. J.; Hudelot, Patrick; Mei, Simona; Toloba, Elisa

2016-11-01

The central region of the Virgo Cluster of galaxies contains thousands of globular clusters (GCs), an order of magnitude more than the number of clusters found in the Local Group. Relics of early star formation epochs in the universe, these GCs also provide ideal targets to test our understanding of the spectral energy distributions (SEDs) of old stellar populations. Based on photometric data from the Next Generation Virgo Cluster Survey (NGVS) and its near-infrared counterpart NGVS-IR, we select a robust sample of ≈ 2000 GCs with excellent photometry and tha span the full range of colors present in the Virgo core. The selection exploits the well-defined locus of GCs in the uiK diagram and the fact that the GCs are marginally resolved in the images. We show that the GCs define a narrow sequence in five-dimensional color space, with limited but real dispersion around the mean sequence. The comparison of these SEDs with the predictions of 11 widely used population synthesis models highlights differences between the models and also shows that no single model adequately matches the data in all colors. We discuss possible causes for some of these discrepancies. Forthcoming papers of this series will examine how best to estimate photometric metallicities in this context, and compare the Virgo GC colors with those in other environments.

Stochastic injection-strategy optimization for the preliminary assessment of candidate geological storage sites

NASA Astrophysics Data System (ADS)

Cody, Brent M.; Baù, Domenico; González-Nicolás, Ana

2015-09-01

Geological carbon sequestration (GCS) has been identified as having the potential to reduce increasing atmospheric concentrations of carbon dioxide (CO2). However, a global impact will only be achieved if GCS is cost-effectively and safely implemented on a massive scale. This work presents a computationally efficient methodology for identifying optimal injection strategies at candidate GCS sites having uncertainty associated with caprock permeability, effective compressibility, and aquifer permeability. A multi-objective evolutionary optimization algorithm is used to heuristically determine non-dominated solutions between the following two competing objectives: (1) maximize mass of CO2 sequestered and (2) minimize project cost. A semi-analytical algorithm is used to estimate CO2 leakage mass rather than a numerical model, enabling the study of GCS sites having vastly different domain characteristics. The stochastic optimization framework presented herein is applied to a feasibility study of GCS in a brine aquifer in the Michigan Basin (MB), USA. Eight optimization test cases are performed to investigate the impact of decision-maker (DM) preferences on Pareto-optimal objective-function values and carbon-injection strategies. This analysis shows that the feasibility of GCS at the MB test site is highly dependent upon the DM's risk-adversity preference and degree of uncertainty associated with caprock integrity. Finally, large gains in computational efficiency achieved using parallel processing and archiving are discussed.

Achilles tendinopathy: A prospective study on the effect of active rehabilitation and steroid injections in a clinical setting.

PubMed

Wetke, E; Johannsen, F; Langberg, H

2015-08-01

In published efficacy studies on Achilles tendinopathy (AT) exercise alone results in improvement in 60-90% of the cases. However, this high success rate cannot be expected in usual clinical practice. We prospectively investigated the effectiveness of a treatment regimen consisting of home-based exercises (concentric, eccentric, and stretching) and optional glucocorticosteroid (GCS) injections in patients with (AT) in a usual clinical setting. Patients unable to commence or progress in exercise were offered GCS, hypothesizing that the GCS would facilitate exercise. Ninety-three consecutive patients with AT referred to two outpatient rheumatology clinics were registered, and seen at five visits over a 6-month period. Exercises seemed to have a slow, but long-lasting effect with GCS having a dramatic short-term effect on symptoms. Twenty-six percent of the patients could proceed with training alone, the remainder received one to three supplementary GCS. There were significant improvements on all outcome variables over time (P ≤ 0.001). At follow-up, 42 had no more symptoms, 29 good result, 16 slightly improved, 4 unchanged, and 2 slightly worse. Overall, 94% of the patients had improved, and we thus recommend the use of GCS injections in AT patients if training alone does not lead to improvement. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Up-regulation of Rho-associated kinase 1/2 by glucocorticoids promotes migration, invasion and metastasis of melanoma.

PubMed

Huang, Gao-Xiang; Wang, Yan; Su, Jie; Zhou, Peng; Li, Bo; Yin, Li-Juan; Lu, Jian

2017-12-01

Although glucocorticoids (GCs) regulate proliferation, differentiation and apoptosis of tumor cells, their influence on metastasis of tumor cells is poorly understood. Melanoma is a type of skin cancers with high metastasis. We investigated the effect of GCs on metastasis of melanoma cells and its mechanism. We found that GCs significantly promoted the adhesion, migration, invasion of melanoma cells in vitro and lung metastasis in experimental melanoma metastasis mice. Dexamethasone (Dex), a synthetic GC, did not change the RhoA, RhoB and RhoC signalings, but significantly increased the expression and activity of Rho-associated kinase 1/2 (ROCK1/2). The effect of Dex was to increase ROCK1/2 stability mediated by glucocorticoid receptor. Inhibiting ROCK1/2 activity with Y-27632, a ROCK1/2 inhibitor abrogated the pro-migration and pro-metastasis effects of GCs in vitro and in vivo, indicating that ROCK1/2 mediated the pro-metastasis effects of GCs. Activation of PI3K/AKT also contributed to the pro-migration and pro-invasion effects of Dex partially through up-regulating ROCK1/2 expression. Additionally, Dex also down-regulated the expression of tissue inhibitors of matrix metalloproteinase-2. Taken together, our findings provide new data to understand the possible promoting roles and mechanisms of GCs in melanoma metastasis. Copyright © 2017. Published by Elsevier B.V.

Chemical abundances of globular clusters in NGC 5128 (Centaurus A)

NASA Astrophysics Data System (ADS)

Hernandez, Svea; Larsen, Søren; Trager, Scott; Kaper, Lex; Groot, Paul

2018-06-01

We perform a detailed abundance analysis on integrated-light spectra of 20 globular clusters (GCs) in the early-type galaxy NGC 5128 (Centaurus A). The GCs were observed with X-Shooter on the Very Large Telescope (VLT). The cluster sample spans a metallicity range of -1.92 < [Fe/H] < -0.13 dex. Using theoretical isochrones, we compute synthetic integrated-light spectra and iterate the individual abundances until the best fit to the observations is obtained. We measured abundances of Mg, Ca, and Ti, and find a slightly higher enhancement in NGC 5128 GCs with metallicities [Fe/H] < -0.75 dex, of the order of ˜0.1 dex, than in the average values observed in the Milky Way (MW) for GCs of the same metallicity. If this α-enhancement in the metal-poor GCs in NGC 5128 is genuine, it could hint at a chemical enrichment history different than that experienced by the MW. We also measure Na abundances in 9 out of 20 GCs. We find evidence for intracluster abundance variations in six of these clusters where we see enhanced [Na/Fe] > +0.25 dex. We obtain the first abundance measurements of Cr, Mn, and Ni for a sample of the GC population in NGC 5128 and find consistency with the overall trends observed in the MW, with a slight enhancement (<0.1 dex) in the Fe-peak abundances measured in the NGC 5128.

Nuclei of dwarf spheroidal galaxies KKs 3 and ESO 269-66 and their counterparts in our Galaxy

NASA Astrophysics Data System (ADS)

Sharina, M. E.; Shimansky, V. V.; Kniazev, A. Y.

2017-10-01

We present the analysis of medium-resolution spectra obtained at the Southern African Large Telescope for nuclear globular clusters (GCs) in two dwarf spheroidal galaxies (dSphs). The galaxies have similar star formation histories, but they are situated in completely different environments. ESO 269-66 is a close neighbour of the giant S0 NGC 5128. KKs 3 is one of the few truly isolated dSphs within 10 Mpc. We estimate the helium abundance Y = 0.3, age = 12.6 ± 1 Gyr, [Fe/H] = -1.5, -1.55 ± 0.2 dex, and abundances of C, N, Mg, Ca, Ti, and Cr for the nuclei of ESO 269-66 and KKs 3. Our surface photometry results using Hubble Space Telescope images yield the half-light radius of the cluster in KKs 3, rh = 4.8 ± 0.2 pc. We demonstrate the similarities of medium-resolution spectra, ages, chemical compositions, and structure for GCs in ESO 269-66 and KKs 3 and for several massive Galactic GCs with [Fe/H] ∼ -1.6 dex. All Galactic GCs posses Extended Blue Horizontal Branches and multiple stellar populations. Five of the selected Galactic objects are iron-complex GCs. Our results indicate that the sample GCs observed now in different environments had similar conditions of their formation ∼1 Gyr after the Big Bang.

Classification of stellar populations in globular clusters

NASA Astrophysics Data System (ADS)

Wang, Yue; Zhao, Gang; Li, Hai-Ning

2017-04-01

Possessing multiple stellar populations has been accepted as a common feature of globular clusters (GCs). Different stellar populations manifest themselves with different chemical features, e.g. the well-known O-Na anti-correlation. Generally, the first (primordial) population has O and Na abundances consistent with those of field stars with similar metallicity; while the second (polluted) population is identified by their Na overabundance and O deficiency. The fraction of the populations is an important constraint on the GC formation scenario. Several methods have been proposed for the classification of GC populations. Here we examine a criterion derived based on the distribution of Galactic field stars, which relies on Na abundance as a function of [Fe/H], to distinguish first and second stellar populations in GCs. By comparing the first population fractions of 17 GCs estimated by the field star criterion with those in the literature derived by methods related to individual GCs, we find that the field star criterion tends to overestimate the first population fractions. The population separation methods, which are related to an individual GC sample, are recommended because the diversity of GCs can be taken into consideration. Currently, more caution should be exercised if one wants to regard field stars as a reference for the identification of a GC population. However, further study on the connection between field stars and GCs populations is still needed.

Genetic Counselors in Startup Companies: Redefining the Genetic Counselor Role.

PubMed

Rabideau, Marina M; Wong, Kenny; Gordon, Erynn S; Ryan, Lauren

2016-08-01

Genetic counselors (GCs) have recently begun moving into non-clinic based roles in increasing numbers. A relatively new role for GCs is working for startup companies. Startups are newly established companies in the phase of developing and researching new scalable businesses. This article explores the experiences of four GCs working at different startup companies and aims to provide resources for GCs interested in learning more about these types of roles. The article describes startup culture, including a relatively flat organizational structure, quick product iterations, and flexibility, among other unique cultural characteristics. Financial considerations are described, including how to understand and evaluate a company's financial status, along with a brief explanation of alternate forms of compensation including stock options and equity. Specifically, the article details the uncertainties and rewards of working in a fast-paced startup environment that affords opportunities to try new roles and use the genetic counseling skill set in new ways. This article aims to aid GCs in determining whether a startup environment would be a good fit, learning how to evaluate a specific startup, and understanding how to market themselves for positions at startups.

Genomic alterations and molecular subtypes of gastric cancers in Asians.

PubMed

Ye, Xiang S; Yu, Chunping; Aggarwal, Amit; Reinhard, Christoph

2016-05-09

Gastric cancer (GC) is a highly heterogenic disease, and it is the second leading cause of cancer death in the world. Common chemotherapies are not very effective for GC, which often presents as an advanced or metastatic disease at diagnosis. Treatment options are limited, and the prognosis for advanced GCs is poor. The landscape of genomic alterations in GCs has recently been characterized by several international cancer genome programs, including studies that focused exclusively on GCs in Asians. These studies identified major recurrent driver mutations and provided new insights into the mutational heterogeneity and genetic profiles of GCs. An analysis of gene expression data by the Asian Cancer Research Group (ACRG) further uncovered four distinct molecular subtypes with well-defined clinical features and their intersections with actionable genetic alterations to which targeted therapeutic agents are either already available or under clinical development. In this article, we review the ACRG GC project. We also discuss the implications of the genetic and molecular findings from various GC genomic studies with respect to developing more precise diagnoses and treatment approaches for GCs.

Ages and chemical compositions of massive globular clusters in NGC147 and M31

NASA Astrophysics Data System (ADS)

Sharina, Margarita; Shimansky, Vladislav

2015-08-01

We present estimates of ages, [Fe/H], helium contents (Y) and abundances of C, N, Mg, Ca, Ti, Cr, Mn, Co and Ni for the following globular clusters (GCs): 7 in NGC147, and Mayall II, Mackey 1 and Mackey 6 in M31. Medium-resolution integrated-light spectra of the GCs were conducted with the 6m telescope. To derive the ages and abundances for the GCs we carried out their population synthesis using model stellar atmospheres, the Padova YZVAR isochrones and the Chabrier mass function. We compare the results with the corresponding data obtained using the same method for several massive Galactic GCs. We show that the differences in the Mg and C abundances between GCs with similar ages and metallicities may reach 0.5-0.6 dex. The corresponding differences for other elements are usually ˜2-3 times smaller. We suggest that at least partially the detected differences may be due to Mg and C abundance variations in the atmospheres of high-luminosity red giant branch stars as a consequence of the transportation of the produced elements to the surface layers.

Ages and chemical compositions of massive clusters in NGC147 and M31

NASA Astrophysics Data System (ADS)

Sharina, Margarita; Shimansky, Vladislav

2017-03-01

We present estimates of ages, [Fe/H], helium content (Y) and abundances of C, N, Mg, Ca, and several other elements for the following globular clusters (GCs): GC7 in NGC147, and Mayall II, Mackey 1 and Mackey 6 in M31. Medium-resolution integrated-light spectra of the GCs were conducted with the 6m telescope. To derive the ages and abundances for the GCs we carried out their population synthesis using model stellar atmospheres, the Padova YZVAR isochrones and the Chabrier mass function. We compare the results with the corresponding data obtained using the same method for several massive Galactic GCs. We show that the differences in the light-element abundances between GCs with similar ages and metallicities may reach 0.5-0.6 dex. The corresponding differences for other elements are usually 2-3 times smaller. We suggest that at least partially the detected differences may be due to light-element abundance variations in the atmospheres of high-luminosity red giant branch stars as a consequence of the transportation of the produced elements to the surface layers.

A Simplified GCS-DCSK Modulation and Its Performance Optimization

NASA Astrophysics Data System (ADS)

Xu, Weikai; Wang, Lin; Chi, Chong-Yung

2016-12-01

In this paper, a simplified Generalized Code-Shifted Differential Chaos Shift Keying (GCS-DCSK) whose transmitter never needs any delay circuits, is proposed. However, its performance is deteriorated because the orthogonality between substreams cannot be guaranteed. In order to optimize its performance, the system model of the proposed GCS-DCSK with power allocations on substreams is presented. An approximate bit error rate (BER) expression of the proposed model, which is a function of substreams’ power, is derived using Gaussian Approximation. Based on the BER expression, an optimal power allocation strategy between information substreams and reference substream is obtained. Simulation results show that the BER performance of the proposed GCS-DCSK with the optimal power allocation can be significantly improved when the number of substreams M is large.

Concentration Dependent Actions of Glucocorticoids on Neuronal Viability and Survival

PubMed Central

Ábrahám, István M; Meerlo, Peter; Luiten, Paul GM

2006-01-01

A growing body of evidence based on experimental data demonstrates that glucocorticoids (GCs) can play a potent role in the survival and death of neurons. However, these observations reflect paradoxical features of GCs, since these adrenal stress hormones are heavily involved in both neurodegenerative and neuroprotective processes. The actual level of GCs appears to have an essential impact in this bimodal action. In the present short review we aim to show the importance of concentration dependent action of GCs on neuronal cell viability and cell survival in the brain. Additionally, we will summarize the possible GC-induced cellular mechanisms at different GC concentrations providing a background for their effect on the fate of nerve cells in conditions that are a challenge to their survival. PMID:18648635

Vitamin D alters genes involved in follicular development and steroidogenesis in human cumulus granulosa cells.

PubMed

Merhi, Zaher; Doswell, Angela; Krebs, Kendall; Cipolla, Marilyn

2014-06-01

Vitamin D deficiency is common among reproductive-aged women and has a role in female reproduction. This study evaluated the role of 1,25-dihydroxyvitamin D3 (vit D3) in ovarian follicular development and steroidogenesis by using a human granulosa cell (GC) model. Fifty-four women who underwent in vitro fertilization were enrolled. Follicular fluid (FF) and mural and cumulus GCs were collected from small and large follicles. In separate experiments, primary cumulus GCs were cultured with or without vit D3 followed by RT-PCR for mRNA expression levels. The effect of recombinant anti-Mullerian hormone (AMH) on nuclear localization of phospho-Smad 1/5/8 was evaluated in the presence or absence of vit D3 by using immunofluorescence. 25-Hydroxyvitamin D levels in FF as well as cell culture media AMH, progesterone, and estradiol (E2) concentrations were determined by ELISA and RIA. The following were measured: 1) mRNA expression levels; 2) 3β-hydroxysteroid dehydrogenase (3β-HSD) enzyme activity; 3) FSH-induced aromatase mRNA and E2 production; and 4) nuclear localization of phospho-Smad 1/5/8. In a multivariate analysis, 25 OH-D levels in FF negatively correlated with AMH and AMH receptor (AMHR)-II mRNA levels in cumulus GCs of small follicles. Compared with women with replete 25-hydroxyvitamin D levels in FF, those with insufficient/deficient levels had a 2-fold increase in AMHR-II mRNA levels in cumulus GCs of small follicles (P = .02). Treatment with vit D3 caused a decrease in AMHR-II and FSH receptor mRNA but an increase in 3-βHSD mRNA levels compared with control (P < .05). Vit D3 enhanced 3-βHSD enzyme activity as assessed by increasing progesterone release; however, vit D3 did not affect FSH-induced aromatase mRNA and E2 production, but it decreased the phosphorylation of Smad 1/5/8 and its nuclear localization. These data suggest that vit D3 alters AMH signaling and steroidogenesis in human cumulus GCs, possibly reflecting a state of GC luteinization potentiation.

The role of fructose‑1,6‑bisphosphatase 1 in abnormal development of ovarian follicles caused by high testosterone concentration.

PubMed

Liu, Tao; Zhao, Han; Wang, Jianfeng; Shu, Xin; Gao, Yuan; Mu, Xiaoli; Gao, Fei; Liu, Hongbin

2017-11-01

The present study aimed to identify the molecular mechanisms underlying the effects of the fructose‑1,6‑bisphosphatase 1 (FBP1) signaling pathway within normal follicle development and in hyperandrogenism‑induced abnormal follicle growth. To achieve this, murine primary follicles, granulosa cells (GCs) and theca‑interstitial cells (TICs) were isolated, cultured in vitro and treated with a high concentration of androgens. A concentration of 1x10‑5 mol/l testosterone was considerable to induce hyperandrogenism by MTT assay. All cells were divided into four groups, as follows: Control group, testosterone group, androgen receptor antagonist‑flutamide group and flutamide + testosterone group. Flutamide was used in the present study as it blocks the effects of the androgen receptor. The mRNA expression levels of FBP1 were detected using reverse transcription‑quantitative polymerase chain reaction. The expression levels and localization of FBP1 were analyzed by western blot analysis and immunofluorescence staining. The experimental results demonstrated that androgen presence stimulated follicle development, whereas excessive testosterone inhibited development. FBP1 was identified as being mainly expressed in follicles; FBP1 protein was significantly expressed in GCs of the 14‑day‑cultured follicle, as well as in the cytoplasm and nuclei of GCs and TICs in vitro. Testosterone increased FBP1 expression during a specific range of testosterone concentrations. Testosterone increased the expression of FBP1 within GCs. Furthermore, FBP1 and phosphoenolpyruvate carboxykinase 1 (PCK1) mRNA expression was increased in GCs treated with testosterone, whereas forkhead box protein O1 (FOXO1) and peroxisome proliferator‑activated receptor γ coactivator‑1α mRNA expression was significantly decreased in the testosterone group. In TICs, testosterone and flutamide inhibited the mRNA expression levels of FOXO1 and glucose‑6‑phosphatase enzyme, and promoted the expression of PCK1. These results suggested that the FBP1 signaling pathway may serve an important role in normal follicle growth and hyperandrogenism‑induced abnormal development, which may be associated with abnormal glucose metabolism induced by high concentrations of testosterone.

MicroRNA-144 is regulated by CP2 and decreases COX-2 expression and PGE2 production in mouse ovarian granulosa cells

PubMed Central

Zhou, Jiawei; Lei, Bin; Li, Huanan; Zhu, Lihua; Wang, Lei; Tao, Hu; Mei, Shuqi; Li, Fenge

2017-01-01

Mammalian folliculogenesis is a complex process in which primordial follicles develop into pre-ovulatory follicles, followed by ovulation to release mature oocytes. In this study, we explored the role of miR-144 in ovulation. miR-144 was one of the differentially expressed microRNAs, which showed 5.59-fold changes, in pre-ovulatory ovarian follicles between Large White and Chinese Taihu sows detected by Solexa deep sequencing. We demonstrated that overexpression of miR-144 significantly decreased the luciferase reporter activity under the control of the cyclooxygenase-2 (COX-2) or mothers against decapentaplegic homologue 4 (Smad4) 3'-untranslated region (3'-UTR) and suppressed COX-2 and Smad4 expression. In contrast, a miR-144 inhibitor increased COX-2 and Smad4 expression in mouse granulosa cells (mGCs). Meanwhile, Smad4 upregulated COX-2 expression, but this effect was abolished when the mGCs were treated with the transforming growth factor beta signalling pathway inhibitor SB431542. Moreover, luciferase reporter, chromatin immunoprecipitation and electrophoretic mobility shift assay results showed that the transcription factor CP2 upregulated miR-144 expression, which partially contributed to the suppression of COX-2 in mGCs. Both CP2 and miR-144 alter prostaglandin E2 (PGE2) production by regulating COX-2 expression. In addition, miR-144 regulated mGC apoptosis and affected follicular atresia, but these activities did not appear to be through COX-2 and Smad4. Taken together, we revealed an important CP2/miR-144/COX-2/PGE2/ovulation pathway in mGCs. PMID:28182010

Evidence for baseline glucocorticoids as mediators of reproductive investment in a wild bird.

PubMed

Love, Oliver P; Madliger, Christine L; Bourgeon, Sophie; Semeniuk, Christina A D; Williams, Tony D

2014-04-01

Determining the mechanisms that mediate investment decisions between current and future reproductive attempts is still a key goal of life-history studies. Since baseline levels of stress hormones (glucocorticoids - GCs) act as predictive and labile regulators of daily energetic balance in vertebrates they remain excellent candidates for mediating investment decisions both within and across reproductive attempts. Using free-living female European starlings (Sturnus vulgaris) we experimentally reduced investment in current reproduction (number of offspring raised in the first brood) to examine whether baseline corticosterone (CORT) acted as a hormonal mediator preparing individuals for a predictable increase in future investment (number of offspring raised in the second brood). Although treatment and control birds raised the same total amount of offspring across two broods, the experimental birds increased reproductive investment in second broods to compensate for the reduced investment in the first brood. Data on both mean and intra-individual changes in baseline CORT support the idea that an increase in baseline CORT between the incubation stages in treatment birds strongly predicted this increase in investment. Importantly, we measured the increase in baseline CORT during late incubation prior to the increase in energetic demand associated with increased reproductive investment in offspring, indicating that flexible within-individual changes in baseline GCs can act as a labile mechanism preparing individuals for predictable increases in reproductive investment. As such, our experimental results indicate that elevated baseline GCs can prepare individuals for investment in energetically expensive life-history stages, rather than simply being elevated as a consequence of increased effort or demand. This suggests that short-term preparative increases in baseline GCs benefit individuals by successfully allowing them to maximize fitness under varying environmental conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

High fat diet triggers cell cycle arrest and excessive apoptosis of granulosa cells during the follicular development

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

Wu, Yanqing; Zhang, Zhenghong; Liao, Xinghui

The regulatory mechanism of granulosa cells (GCs) proliferation during the follicular development is complicated and multifactorial, which is essential for the oocyte growth and normal ovarian functions. To investigate the role of high fat diet (HFD) on the proliferation of GCs, 4-week old female mice were fed with HFD or normal control diet (NC) for 15 weeks or 20 weeks and then detected the expression level of some regulatory molecules of cell cycle and apoptosis. The abnormal ovarian morphology was observed at 20 weeks. Further mechanistic studies indicated that HFD induced-obesity caused elevated apoptotic levels in GCs of the ovariesmore » in a time-dependent manner. Moreover, cell cycle progress was also impacted after HFD fed. The cell cycle inhibitors, p27{sup Kip1} and p21{sup Cip1}, were significantly induced in the ovaries from the mice in HFD group when compared with that in the ovaries from the mice in NC group. Subsequently, the expression levels of Cyclin D1, D3 and CDK4 were also significantly influenced in the ovaries from the mice fed with HFD in a time-dependent manner. The present results suggested that HFD induced-obesity may trigger cell cycle arrest and excessive apoptosis of GCs, causing the abnormal follicular development and ovarian function failure. - Highlights: • HFD induced-obesity leads to abnormal ovarian morphology. • HFD induced-obesity triggers excessive apoptosis in the ovary. • HFD induced-obesity up-regulates cell cycle inhibitors p21{sup Cip1} and p27{sup Kip1} in the ovary. • HFD induced-obesity causes cell cycle arrest in the ovary.« less

Homeostasis or channelopathy? Acquired cell type-specific ion channel changes in temporal lobe epilepsy and their antiepileptic potential

PubMed Central

Wolfart, Jakob; Laker, Debora

2015-01-01

Neurons continuously adapt the expression and functionality of their ion channels. For example, exposed to chronic excitotoxicity, neurons homeostatically downscale their intrinsic excitability. In contrast, the “acquired channelopathy” hypothesis suggests that proepileptic channel characteristics develop during epilepsy. We review cell type-specific channel alterations under different epileptic conditions and discuss the potential of channels that undergo homeostatic adaptations, as targets for antiepileptic drugs (AEDs). Most of the relevant studies have been performed on temporal lobe epilepsy (TLE), a widespread AED-refractory, focal epilepsy. The TLE patients, who undergo epilepsy surgery, frequently display hippocampal sclerosis (HS), which is associated with degeneration of cornu ammonis subfield 1 pyramidal cells (CA1 PCs). Although the resected human tissue offers insights, controlled data largely stem from animal models simulating different aspects of TLE and other epilepsies. Most of the cell type-specific information is available for CA1 PCs and dentate gyrus granule cells (DG GCs). Between these two cell types, a dichotomy can be observed: while DG GCs acquire properties decreasing the intrinsic excitability (in TLE models and patients with HS), CA1 PCs develop channel characteristics increasing intrinsic excitability (in TLE models without HS only). However, thorough examination of data on these and other cell types reveals the coexistence of protective and permissive intrinsic plasticity within neurons. These mechanisms appear differentially regulated, depending on the cell type and seizure condition. Interestingly, the same channel molecules that are upregulated in DG GCs during HS-related TLE, appear as promising targets for future AEDs and gene therapies. Hence, GCs provide an example of homeostatic ion channel adaptation which can serve as a primer when designing novel anti-epileptic strategies. PMID:26124723

Hubble Space Telescope Snapshot Search for Planetary Nebulae in Globular Clusters of the Local Group

NASA Astrophysics Data System (ADS)

Bond, Howard E.

2015-04-01

Single stars in ancient globular clusters (GCs) are believed incapable of producing planetary nebulae (PNs), because their post-asymptotic-giant-branch evolutionary timescales are slower than the dissipation timescales for PNs. Nevertheless, four PNs are known in Galactic GCs. Their existence likely requires more exotic evolutionary channels, including stellar mergers and common-envelope binary interactions. I carried out a snapshot imaging search with the Hubble Space Telescope (HST) for PNs in bright Local Group GCs outside the Milky Way. I used a filter covering the 5007 Å nebular emission line of [O iii], and another one in the nearby continuum, to image 66 GCs. Inclusion of archival HST frames brought the total number of extragalactic GCs imaged at 5007 Å to 75, whose total luminosity slightly exceeds that of the entire Galactic GC system. I found no convincing PNs in these clusters, aside from one PN in a young M31 cluster misclassified as a GC, and two PNs at such large angular separations from an M31 GC that membership is doubtful. In a ground-based spectroscopic survey of 274 old GCs in M31, Jacoby et al. found three candidate PNs. My HST images of one of them suggest that the [O iii] emission actually arises from ambient interstellar medium rather than a PN; for the other two candidates, there are broadband archival UV HST images that show bright, blue point sources that are probably the PNs. In a literature search, I also identified five further PN candidates lying near old GCs in M31, for which follow-up observations are necessary to confirm their membership. The rates of incidence of PNs are similar, and small but nonzero, throughout the GCs of the Local Group. Based on observations with the NASA/ESA Hubble Space Telescope obtained at the Space Telescope Science Institute, and from the data archive at STScI, which are operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5-26555.

Metallicity Variations in the Type II Globular Cluster NGC 6934

NASA Astrophysics Data System (ADS)

Marino, A. F.; Yong, D.; Milone, A. P.; Piotto, G.; Lundquist, M.; Bedin, L. R.; Chené, A.-N.; Da Costa, G.; Asplund, M.; Jerjen, H.

2018-06-01

The Hubble Space Telescope photometric survey of Galactic globular clusters (GCs) has revealed a peculiar “chromosome map” for NGC 6934. In addition to a typical sequence, similar to that observed in Type I GCs, NGC 6934 displays additional stars on the red side, analogous to the anomalous Type II GCs, as defined in our previous work. We present a chemical abundance analysis of four red giants in this GC. Two stars are located on the chromosome map sequence common to all GCs, and another two lie on the additional sequence. We find (i) star-to-star Fe variations, with the two anomalous stars being enriched by ∼0.2 dex. Because of our small-size sample, this difference is at the ∼2.5σ level. (ii) There is no evidence for variations in the slow neutron-capture abundances over Fe, at odds with what is often observed in anomalous Type II GCs, e.g., M 22 and ω Centauri (iii) no large variations in light elements C, O, and Na, compatible with locations of the targets on the lower part of the chromosome map where such variations are not expected. Since the analyzed stars are homogeneous in light elements, the only way to reproduce the photometric splits on the sub-giant (SGB) and the red giant (RGB) branches is to assume that red RGB/faint SGB stars are enhanced in [Fe/H] by ∼0.2. This fact corroborates the spectroscopic evidence of a metallicity variation in NGC 6934. The observed chemical pattern resembles only partially the other Type II GCs, suggesting that NGC 6934 might belong either to a third class of GCs, or be a link between normal Type I and anomalous Type II GCs. Based on observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by AURA, Inc., under NASA contract NAS 5-26555. This paper includes data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile, and Gemini Telescope at Canada–France–Hawaii Telescope.

A VST and VISTA study of globular clusters in NGC 253

NASA Astrophysics Data System (ADS)

Cantiello, Michele; Grado, Aniello; Rejkuba, Marina; Arnaboldi, Magda; Capaccioli, Massimo; Greggio, Laura; Iodice, Enrica; Limatola, Luca

2018-03-01

Context. Globular clusters (GCs) are key to our understanding of the Universe, as laboratories of stellar evolution, fossil tracers of the past formation epoch of the host galaxy, and effective distance indicators from local to cosmological scales. Aim. We analyze the properties of the sources in the NGC 253 with the aim of defining an up to date catalog of GC candidates in the galaxy. Given the distance of the galaxy, GCs in NGC 253 are ideal targets for resolved color-magnitude diagram studies of extragalactic GCs with next-generation diffraction limited ground-based telescopes. Methods: Our analysis is based on the science verification data of two ESO survey telescopes, VST and VISTA. Using ugri photometry from VST and JKs from VISTA, GC candidates were selected using as reference the morpho-photometric and color properties of spectroscopically confirmed GCs available in the literature. The strength of the results was verified against available archival HST/ACS data from the GHOSTS survey: all but two of the selected GC candidates appear as star clusters in HST footprints. Results: The adopted GC selection leads to the definition of a sample of ˜350 GC candidates. At visual inspection, we find that 82 objects match all the requirements for selecting GC candidates and 155 are flagged as uncertain GC candidate; however, 110 are unlikely GCs, which are most likely background galaxies. Furthermore, our analysis shows that four of the previously spectroscopically confirmed GCs, i.e., ˜20% of the total spectroscopic sample, are more likely either background galaxies or high-velocity Milky Way stars. The radial density profile of the selected best candidates shows the typically observed r1/4-law radial profile. The analysis of the color distributions reveals only marginal evidence of the presence of color bimodality, which is normally observed in galaxies of similar luminosity. The GC luminosity function does not show the typical symmetry, mainly because of the lack of bright GCs. Part of the bright GCs missing might be at very large galactocentric distances or along the line of sight of the galaxy dusty disk. As an alternative possibility, we speculate that a fraction of low luminosity GC candidates might instead be metal-rich, intermediate age clusters, but fall in a similar color interval of old, metal-poor GCs. Conclusions: Defining a contaminant-free sample of GCs in extragalactic systems is not a straight forward exercise. Using optical and near-IR photometry we purged the list of GCs with spectroscopic membership and photometric GC candidates in NGC 253. Our results show that the use of either spectroscopic or photometric data only does not generally ensure a contaminant-free sample and a combination of both spectroscopy and photometry is preferred. Table 3 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/611/A21This work is based on observations taken at the ESO La Silla Paranal Observatory within the VST Science Verification Programme ID 60.A-9286(A) and VISTA Science Verification Programme ID 60.A-9285(A).

The Effect of Whole Body Massage on the Process and Physiological Outcome of Trauma ICU Patients: A Double-Blind Randomized Clinical Trial

PubMed Central

Hatefi, Masoud; Jaafarpour, Molouk; Khajavikhan, Javaher; Kokhazade, Taleb

2015-01-01

Background and Aim Hospitalization of traumatic patients in the Intensive Care Unit (ICU) and their critical condition can cause haemodynamic instabilities and deterioration in the level of consciousness. The study aimed to investigate the effect of whole body massage on the vital signs, Glasgow Coma Scale (GCS) scores and arterial blood gases (ABG) in trauma ICU patients. Materials and Methods In a randomized, double-blind trial, 108 trauma ICU patients received whole body massage {experimental group (n=54)}, or routine care {control group (n=54)}. The patients vital signs; systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR), pulse rate (PR), Temperature (T), GCS score and ABG parameters were measured by a nurse at the same time in both groups before the intervention and 1 hour and 3 hours after the intervention with a checklist. The patient in experimental group received full body massage in 45 minute by a family member. Results According to the findings, significant differences were observed between experimental and control groups in SBP 1 hour and 3 hours after intervention (p< 0.001), DBP, RR and PR 1 hour after intervention (p<0.001) and GCS 1 hour and 3 hours after intervention (p<0.05). Of ABG parameters, significant differences were observed between experimental and control groups in O2 saturation (p<0.001), PH (p<0.001) and pO2 (p<0.05). No significant differences between experimental and control groups in Temperature, pCO2 and HCO3 (p>0.05). Conclusion With respect to this study, massage therapy is a safe and effective treatment in intensive care units to reduce patient’s physical and psychological problems. Therefore the use of massage therapy is recommended to clinical practice as a routine method. PMID:26266191

Ikhana: A NASA UAS Supporting Long Duration Earth Science Missions

NASA Technical Reports Server (NTRS)

Cobleigh, Brent R.

2006-01-01

NASA's Ikhana unmanned aerial vehicle (UAV) is a General Atomics MQ-9 Predator-B modified to support the conduct of Earth science missions for the NASA Science Mission Directorate through partnerships, other government agencies and universities. Ikhana, a Native American word meaning 'intelligence', can carry over 2000 lbs of atmospheric and remote sensing instruments in the payload bay and external pods. The aircraft is capable of mission durations in excess of 24 hours at altitudes above 40,000 ft. Redundant flight control, avionics, power, and network systems increase the system reliability and allow easier access to public airspace. The aircraft is remotely piloted from a mobile ground control station (GCS) using both C-band line-of-sight and Ku-band over-the-horizon satellite datalinks. NASA's GCS has been modified to support on-site science monitoring, or the downlink data can be networked to remote sites. All ground support systems are designed to be deployable to support global Eart science investigations. On-board support capabilities include an instrumentation system and an Airborne Research Test System (ARTS). The ARTS can host research algorithms that will autonomously command and control on-board sensors, perform sensor health monitoring, conduct data analysis, and request changes to the flight plan to maximize data collection. The ARTS also has the ability to host algorithms that will autonomously control the aircraft trajectory based on sensor needs, (e.g. precision trajectory for repeat pass interferometry) or to optimize mission objectives (e.g. search for specific atmospheric conditions). Standard on-board networks will collect science data for recording and for inclusion in the aircraft's high bandwidth downlink. The Ikhana project will complete GCS development, science support systems integration, external pod integration and flight clearance, and operations crew training in early 2007. A large-area remote sensing mission is currently scheduled for the Summer 2007.

Biochemistry and physiology of hexose-6-phosphate knockout mice.

PubMed

Zielinska, Agnieszka E; Walker, Elizabeth A; Stewart, Paul M; Lavery, Gareth G

2011-04-10

Hexose-6-phosphate dehydrogenase (H6PDH) has emerged as an important factor in setting the redox status of the endoplasmic reticulum (ER) lumen. An important role of H6PDH is to generate a high NADPH/NADP(+) ratio which permits 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) to act as an oxo-reductase, catalyzing the activation of glucocorticoids (GCs). In H6PDH knockout mice 11β-HSD1 assumes dehydrogenase activity and inactivates GCs, rendering the target cell relatively GC insensitive. Consequently, H6PDHKO mice have a phenotype consistent with defects in the permissive and adaptive actions of GCs upon physiology. H6PDHKO mice have also offered an insight into muscle physiology as they also present with a severe vacuolating myopathy, abnormalities of glucose homeostasis and activation of the unfolded protein response due to ER stress, and a number of mechanisms driving this phenotype are thought to be involved. This article will review what we understand of the redox control of GC hormone metabolism regulated by H6PDH, and how H6PDHKO mice have allowed an in-depth understanding of its potentially novel, GC-independent roles in muscle physiology. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

In vivo blockade of acetylcholinesterase increases intraovarian acetylcholine and enhances follicular development and fertility in the rat.

PubMed

Urra, Javier; Blohberger, Jan; Tiszavari, Michelle; Mayerhofer, Artur; Lara, Hernan E

2016-07-21

Growth and differentiation of ovarian follicles are regulated by systemic and local factors, which may include acetylcholine (ACh). Granulosa cells (GCs) of growing follicles and luteal cells produce ACh and in cultured GCs it exerts trophic actions via muscarinic receptors. However, such actions were not studied in vivo. After having established that rat ovarian GCs and luteal cells express the ACh-metabolizing enzyme ACh esterase (AChE), we examined the consequences of local application of an AChE inhibitor, huperzine A (HupA), by osmotic minipump delivery into the ovarian bursa of hemiovariectomized rats. Saline was used in the control group. Local delivery of HupA for 4 weeks increased ovarian ACh content. Estrus cyclicity was not changed indicating a locally restricted range of HupA action. The number of primordial and primary follicles was unaffected, but small secondary follicles significantly increased in the HupA group. Furthermore, a significant increase in the number of corpora lutea suggested increased ovulatory events. In support, as shown upon mating, HupA-treated females had significantly increased implantation sites and more pups. Thus the data are in support of a trophic role of ACh in follicular development and ovulation and point to an important role of ACh in female fertility.

In vivo blockade of acetylcholinesterase increases intraovarian acetylcholine and enhances follicular development and fertility in the rat

PubMed Central

Blohberger, Jan; Tiszavari, Michelle; Mayerhofer, Artur; Lara, Hernan E.

2016-01-01

Growth and differentiation of ovarian follicles are regulated by systemic and local factors, which may include acetylcholine (ACh). Granulosa cells (GCs) of growing follicles and luteal cells produce ACh and in cultured GCs it exerts trophic actions via muscarinic receptors. However, such actions were not studied in vivo. After having established that rat ovarian GCs and luteal cells express the ACh-metabolizing enzyme ACh esterase (AChE), we examined the consequences of local application of an AChE inhibitor, huperzine A (HupA), by osmotic minipump delivery into the ovarian bursa of hemiovariectomized rats. Saline was used in the control group. Local delivery of HupA for 4 weeks increased ovarian ACh content. Estrus cyclicity was not changed indicating a locally restricted range of HupA action. The number of primordial and primary follicles was unaffected, but small secondary follicles significantly increased in the HupA group. Furthermore, a significant increase in the number of corpora lutea suggested increased ovulatory events. In support, as shown upon mating, HupA-treated females had significantly increased implantation sites and more pups. Thus the data are in support of a trophic role of ACh in follicular development and ovulation and point to an important role of ACh in female fertility. PMID:27440195

Traumatic acute subdural haematomas of the posterior fossa: clinicoradiological analysis of 24 patients.

PubMed

d'Avella, D; Servadei, F; Scerrati, M; Tomei, G; Brambilla, G; Massaro, F; Stefini, R; Cristofori, L; Conti, A; Cardali, S; Tomasello, F

2003-12-01

We report 24 patients with a traumatic acute subdural haematoma of the posterior fossa managed between 1997 and 1999 at 8 Italian neurosurgical centres. Each centre provided data about patients' clinico-radiological findings, management, and outcomes, which were retrospectively reviewed. A poor result occurred in 14 patients (58.3%). Ten patients (41.7%) had favourable results. Patients were divided into two groups according to their admission Glasgow Coma Scale (GCS) scores. In Group 1 (12/24 cases; GCS score, > or =8), the outcome was favourable in 75% of cases. In Group 2 (12/12 cases; GCS score, <8), the outcome was poor in 91.6% of cases. Nineteen patients underwent posterior fossa surgery. Factors correlating to outcome were GCS score, status of the basal cisterns and the fourth ventricle, and the presence of supratentorial hydrocephalus. Multivariate analysis showed significant independent prognostic effect only for GCS score (P<0.05). acute posterior fossa subdural haematomas can be divided into two distinct groups: those patients admitted in a comatose state and those with a moderate/mild head injury on admission. Comatose patients present usually with signs of posterior fossa mass effect and have a high percentage of bad outcomes. On the contrary, patients admitted with a GCS of 8 or higher are expected to recover. In these patients the thickness of the haematoma (<1 cm) seems to be a guide to indicate surgical evacuation of the haematoma.

Do cortisol and corticosterone play the same role in coping with stressors? Measuring glucocorticoid serum in free-ranging guanacos (Lama guanicoe).

PubMed

Ovejero, Ramiro; Novillo, Agustina; Soto-Gamboa, Mauricio; Mosca-Torres, Maria E; Cuello, Pablo; Gregório, Pablo; Jahn, Graciela; Carmanchahi, Pablo

2013-12-01

Habitat can constrain and shape successful ecological and physiological strategies, thus providing the context for the evolution of life-history traits. However, unpredictable challenges, such as storms, natural disasters, and human activities can also have great effects on stress. Glucocorticoids (GCs) are adrenal steroid hormones that play an important role in how vertebrates cope with these predictable and unpredictable environmental challenges. Although assessing GCs levels can have many applications in the study of wildlife and/or captive animals, with or without capturing individuals, it requires a species-specific complete validation (analytical and biological) before its use. In this work, our aim was to: (a) validate a radioimmunoassay (RIA) for measuring GCs levels in L. guanicoe serum; (b) assess cortisol and corticosterone levels (if present) in serum of wild L. guanicoe individuals; and (c) compare the response to acute stressors (handling, shearing, and release). Our results successfully: (a) validated RIA for asses GCs levels in wild ungulates; (b) confirmed the presence for cortisol and corticosterone and showed that both GCs are differently affected by environmental stimuli in L. guanicoe; and (c) showed that GCs exhibit different patterns in the field and in response to acute stressors, making these camelids an interesting endocrinological model when seeking the adaptive functions of a given variation and further emphasizing the complexity of GC physiology in wild mammals. © 2013 Wiley Periodicals, Inc.

[Interobserver reliability of the Glasgow coma scale in critically ill patients with neurological and/or neurosurgical disease].

PubMed

Sánchez-Sánchez, M M; Sánchez-Izquierdo, R; Sánchez-Muñoz, E I; Martínez-Yegles, I; Fraile-Gamo, M P; Arias-Rivera, S

2014-01-01

The Glasgow coma scale (GCS) is a common tool used for neurological assessment of critically ill patients. Despite its widespread use, the GCS has some limitations, as sometimes different observers may value differently the same response. To evaluate the interobserver agreement, among intensive care nurses with a minimum of 3 years experience, both in the overall estimate of GCS and for each of its components. Prospective observational study including 110 neurological and/or neurosurgical patients conducted in a critical care unit of 18 beds, from October 2010 until December 2012. Registered variables: Demographic characteristics, reason for admission, overall GCS and its components. The neurological evaluation was conducted by a minimum of 3 nurses. One of them applied an algorithm and consensual assessment technique and all, independently, valued response to stimuli. Interobserver agreement was measured using the intraclass correlation coefficient (ICC) for a confidence interval (CI) of 95%. The study was approved by the Ethics Committee for Clinical Trails. The intraclass correlation coefficient (confident interval) for scale was: Overall GCS: 0.989 (0.985-0.992); ocular response: 0.981 (0.974-0.986); verbal response: 0.971 (0.960-0.979); motor response: 0.987 (0.982-0.991). In our cohort of patients we observed a high level of consistency in the application of both the GCS as in each of its components. Copyright © 2013 Elsevier España, S.L. y SEEIUC. All rights reserved.

DERIVING METALLICITIES FROM THE INTEGRATED SPECTRA OF EXTRAGALACTIC GLOBULAR CLUSTERS USING THE NEAR-INFRARED CALCIUM TRIPLET

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

Foster, Caroline; Forbes, Duncan A.; Proctor, Robert N.

2010-04-15

The Ca II triplet (CaT) feature in the near-infrared has been employed as a metallicity indicator for individual stars as well as integrated light of Galactic globular clusters (GCs) and galaxies with varying degrees of success, and sometimes puzzling results. Using the DEIMOS multi-object spectrograph on Keck we obtain a sample of 144 integrated light spectra of GCs around the brightest group galaxy NGC 1407 to test whether the CaT index can be used as a metallicity indicator for extragalactic GCs. Different sets of single stellar population models make different predictions for the behavior of the CaT as a functionmore » of metallicity. In this work, the metallicities of the GCs around NGC 1407 are obtained from CaT index values using an empirical conversion. The measured CaT/metallicity distributions show unexpected features, the most remarkable being that the brightest red and blue GCs have similar CaT values despite their large difference in mean color. Suggested explanations for this behavior in the NGC 1407 GC system are (1) the CaT may be affected by a population of hot blue stars, (2) the CaT may saturate earlier than predicted by the models, and/or (3) color may not trace metallicity linearly. Until these possibilities are understood, the use of the CaT as a metallicity indicator for the integrated spectra of extragalactic GCs will remain problematic.« less

Predictive Value of Glasgow Coma Score and Full Outline of Unresponsiveness Score on the Outcome of Multiple Trauma Patients.

PubMed

Baratloo, Alireza; Shokravi, Masumeh; Safari, Saeed; Aziz, Awat Kamal

2016-03-01

The Full Outline of Unresponsiveness (FOUR) score was developed to compensate for the limitations of Glasgow coma score (GCS) in recent years. This study aimed to assess the predictive value of GCS and FOUR score on the outcome of multiple trauma patients admitted to the emergency department. The present prospective cross-sectional study was conducted on multiple trauma patients admitted to the emergency department. GCS and FOUR scores were evaluated at the time of admission and at the sixth and twelfth hours after admission. Then the receiver operating characteristic (ROC) curve, sensitivity, specificity, as well as positive and negative predictive value of GCS and FOUR score were evaluated to predict patients' outcome. Patients' outcome was divided into discharge with and without a medical injury (motor deficit, coma or death). Finally, 89 patients were studied. Sensitivity and specificity of GCS in predicting adverse outcome (motor deficit, coma or death) were 84.2% and 88.6% at the time of admission, 89.5% and 95.4% at the sixth hour and 89.5% and 91.5% at the twelfth hour, respectively. These values for the FOUR score were 86.9% and 88.4% at the time of admission, 89.5% and 100% at the sixth hour and 89.5% and 94.4% at the twelfth hour, respectively. Findings of this study indicate that the predictive value of FOUR score and GCS on the outcome of multiple trauma patients admitted to the emergency department is similar.

Gastric cancer in young vs old Romanian patients: immunoprofile with emphasis on maspin and mena protein reactivity.

PubMed

Gurzu, Simona; Kadar, Zoltan; Sugimura, Haruhiko; Bara, Tivadar; Bara, Tivadar; Halmaciu, Ioana; Jung, Ioan

2015-03-01

Increasing number of early-onset gastric carcinomas (GCs) and controversial results regarding the differences among young and older patients with this type of cancer are the reasons why correlation of clinicopathological factors with molecular markers is necessary. The aim of our study was to compare the demographic, clinical and immunohistochemical (IHC) aspects in Romanian patients with GC diagnosed below and above 45 years old. In 191 samples provided from patients with GC, the clinicopathological parameters were correlated with a panel of 15 antibodies: E-cadherin, HER-2, VEGF, CD31, CD105, COX-2, maspin, bax, bcl-2, p53, Ki67, MLH-1, MSH-2, mena protein and vimentin. Compared to the conventional cases, GCs diagnosed below 45 years old were more frequently located at the gastroesophageal junction and presented a higher percentage of lymph node metastases. The diffuse type E-cadherin/mena/p53/Ki67/bax-negative cases that displayed nuclear maspin positivity were also more frequently in younger patients. The intestinal type early-onset GCs were the most angiogenic ones, the apoptotic rate being lower than in the intestinal type GCs of the aged. Compared to the conventional cases, in the early-onset GCs the nuclear maspin-mediated antiproliferative activity is more intense in diffuse type while the mena-dependent tumor cell proliferation is more characteristic for intestinal type GCs. © 2014 APMIS. Published by John Wiley & Sons Ltd.

ARE SOME MILKY WAY GLOBULAR CLUSTERS HOSTED BY UNDISCOVERED GALAXIES?

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

Zaritsky, Dennis; Crnojević, Denija; Sand, David J., E-mail: dennis.zaritsky@gmail.com

2016-07-20

The confirmation of a globular cluster (GC) in the recently discovered ultrafaint galaxy Eridanus II (Eri II) motivated us to examine the question posed in the title. After estimating the halo mass of Eri II using a published stellar mass—halo mass relation, the one GC in this galaxy supports extending the relationship between the number of GCs hosted by a galaxy and the galaxy’s total mass about two orders of magnitude in stellar mass below the previous limit. For this empirically determined specific frequency of between 0.06 and 0.39 GCs per 10{sup 9} M {sub ⊙} of total mass, themore » surviving Milky Way (MW) subhalos with masses smaller than 10{sup 10} M {sub ⊙} could host as many as 5–31 GCs, broadly consistent with the actual population of outer halo MW GCs, although matching the radial distribution in detail remains a challenge. Using a subhalo mass function from published high-resolution numerical simulations and a Poissonian model for populating those halos with the aforementioned empirically constrained frequency, we find that about 90% of these GCs lie in lower-mass subhalos than that of Eri II. From what we know about the stellar mass–halo mass function, the subhalo mass function, and the mass-normalized GC specific frequency, we conclude that some of the MW’s outer halo GCs are likely to be hosted by undetected subhalos with extremely modest stellar populations.« less

Acute restraint stress decreases c-fos immunoreactivity in hilar mossy cells of the adult dentate gyrus

PubMed Central

Moretto, Jillian N.; Duffy, Áine M.

2017-01-01

Although a great deal of information is available about the circuitry of the mossy cells (MCs) of the dentate gyrus (DG) hilus, their activity in vivo is not clear. The immediate early gene c-fos can be used to gain insight into the activity of MCs in vivo, because c-fos protein expression reflects increased neuronal activity. In prior work, it was identified that control rats that were perfusion-fixed after removal from their home cage exhibited c-fos immunoreactivity (ir) in the DG in a spatially stereotyped pattern: ventral MCs and dorsal granule cells (GCs) expressed c-fos protein (Duffy et al., Hippocampus 23:649–655, 2013). In this study, we hypothesized that restraint stress would alter c-fos-ir, because MCs express glucocorticoid type 2 receptors and the DG is considered to be involved in behaviors related to stress or anxiety. We show that acute restraint using a transparent nose cone for just 10 min led to reduced c-fos-ir in ventral MCs compared to control rats. In these comparisons, c-fos-ir was evaluated 30 min after the 10 min-long period of restraint, and if evaluation was later than 30 min c-fos-ir was no longer suppressed. Granule cells (GCs) also showed suppressed c-fos-ir after acute restraint, but it was different than MCs, because the suppression persisted for over 30 min after the restraint. We conclude that c-fos protein expression is rapidly and transiently reduced in ventral hilar MCs after a brief period of restraint, and suppressed longer in dorsal GCs. PMID:28190104

Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1.

PubMed

Merhi, Zaher; Thornton, Kimberley; Bonney, Elizabeth; Cipolla, Marilyn J; Charron, Maureen J; Buyuk, Erkan

2016-04-01

The objective of this study was to test the hypothesis that ovarian kisspeptin (kiss1) and its receptor (kiss1r) expression are affected by age, obesity, and the age- and obesity-related chemokine monocyte chemoattractant protein-1 (MCP-1). Ovaries from reproductive-aged and older C57BL/6J mice fed normal chow (NC) or high-fat (HF) diet, ovaries from age-matched young MCP-1 knockout and young control mice on NC, and finally, cumulus and mural granulosa cells (GCs) from women who underwent in vitro fertilization (IVF) were collected. Kiss1, kiss1r, anti-Mullerian hormone (AMH), and AMH receptor (AMHR-II) messenger RNA (mRNA) expression levels were quantified using real-time polymerase chain reaction (RT-PCR). In mouse ovaries, kiss1 and kiss1r mRNA levels were significantly higher in old compared to reproductive-aged mice, and diet-induced obesity did not alter kiss1 or kiss1r mRNA levels. Compared to young control mice, young MCP-1 knockout mice had significantly lower ovarian kiss1 mRNA but significantly higher AMH and AMHR-II mRNA levels. In human cumulus GCs, kiss1r mRNA levels were positively correlated with age but not with BMI. There was no expression of kiss1 mRNA in either cumulus or mural GCs. These data suggest a possible age-related physiologic role for the kisspeptinergic system in ovarian physiology. Additionally, the inflammatory MCP-1 may be associated with kiss1 and AMH genes, which are important in ovulation and folliculogenesis, respectively.

Analysis of three surgical treatments for spontaneous supratentorial intracerebral hemorrhage.

PubMed

Cai, Qiang; Zhang, Huaping; Zhao, Dong; Yang, Zhaohui; Hu, Keqi; Wang, Long; Zhang, Wenfei; Chen, Zhibiao; Chen, Qianxue

2017-10-01

This retrospective study aimed to evaluate the effectiveness and safety of 3 surgical procedures for Spontaneous Supratentorial Intracerebral Hemorrhage (SICH).A total of 63 patients with SICH were randomized into 3 groups. Group A (n = 21) underwent craniotomy surgery, group B (n = 22) underwent burr hole, urokinase infusion and catheter drainage, and group C (n = 20) underwent neuroendoscopic surgery. The hematoma evacuation rate of the operation was analyzed by 3D Slice software and the average surgery time, visualization during operation, decompressive effect, mortality, Glasgow Coma Scale (GCS) improvement, complications include rebleeding, pneumonia, intracranial infection were also compared among 3 groups.All procedures were successfully completed and the hematoma evacuation rate was significant differences among 3 groups which were 79.8%, 43.1%, 89.3% respectively (P < .01), and group C was the highest group. Group B was smallest traumatic one and shared the shortest operation time, but for the lack of hemostasis, it also the highest rebleeding group (P = .03). Although there were different in complications, but there was no significant in pneumonia, intracranial infection, GCS improvement and mortality rate.All these 3 methods had its own advantages and shortcomings, and every approach had its indications for SICH. Although for neuroendoscopic technical's minimal invasive, direct vision, effectively hematoma evacuation rate, and the relatively optimistic result, it might be a more promising approach for SICH.

Analysis of three surgical treatments for spontaneous supratentorial intracerebral hemorrhage

PubMed Central

Cai, Qiang; Zhang, Huaping; Zhao, Dong; Yang, Zhaohui; Hu, Keqi; Wang, Long; Zhang, Wenfei; Chen, Zhibiao; Chen, Qianxue

2017-01-01

Abstract This retrospective study aimed to evaluate the effectiveness and safety of 3 surgical procedures for Spontaneous Supratentorial Intracerebral Hemorrhage (SICH). A total of 63 patients with SICH were randomized into 3 groups. Group A (n = 21) underwent craniotomy surgery, group B (n = 22) underwent burr hole, urokinase infusion and catheter drainage, and group C (n = 20) underwent neuroendoscopic surgery. The hematoma evacuation rate of the operation was analyzed by 3D Slice software and the average surgery time, visualization during operation, decompressive effect, mortality, Glasgow Coma Scale (GCS) improvement, complications include rebleeding, pneumonia, intracranial infection were also compared among 3 groups. All procedures were successfully completed and the hematoma evacuation rate was significant differences among 3 groups which were 79.8%, 43.1%, 89.3% respectively (P < .01), and group C was the highest group. Group B was smallest traumatic one and shared the shortest operation time, but for the lack of hemostasis, it also the highest rebleeding group (P = .03). Although there were different in complications, but there was no significant in pneumonia, intracranial infection, GCS improvement and mortality rate. All these 3 methods had its own advantages and shortcomings, and every approach had its indications for SICH. Although for neuroendoscopic technical's minimal invasive, direct vision, effectively hematoma evacuation rate, and the relatively optimistic result, it might be a more promising approach for SICH. PMID:29069046

Semaphorin 5A inhibits synaptogenesis in early postnatal- and adult-born hippocampal dentate granule cells.

PubMed

Duan, Yuntao; Wang, Shih-Hsiu; Song, Juan; Mironova, Yevgeniya; Ming, Guo-li; Kolodkin, Alex L; Giger, Roman J

2014-10-14

Human SEMAPHORIN 5A (SEMA5A) is an autism susceptibility gene; however, its function in brain development is unknown. In this study, we show that mouse Sema5A negatively regulates synaptogenesis in early, developmentally born, hippocampal dentate granule cells (GCs). Sema5A is strongly expressed by GCs and regulates dendritic spine density in a cell-autonomous manner. In the adult mouse brain, newly born Sema5A-/- GCs show an increase in dendritic spine density and increased AMPA-type synaptic responses. Sema5A signals through PlexinA2 co-expressed by GCs, and the PlexinA2-RasGAP activity is necessary to suppress spinogenesis. Like Sema5A-/- mutants, PlexinA2-/- mice show an increase in GC glutamatergic synapses, and we show that Sema5A and PlexinA2 genetically interact with respect to GC spine phenotypes. Sema5A-/- mice display deficits in social interaction, a hallmark of autism-spectrum-disorders. These experiments identify novel intra-dendritic Sema5A/PlexinA2 interactions that inhibit excitatory synapse formation in developmentally born and adult-born GCs, and they provide support for SEMA5A contributions to autism-spectrum-disorders.

Stress and Memory: A Selective Review on Recent Developments in the Understanding of Stress Hormone Effects on Memory and Their Clinical Relevance.

PubMed

Wolf, O T; Atsak, P; de Quervain, D J; Roozendaal, B; Wingenfeld, K

2016-08-01

Stress causes a neuroendocrine response cascade, leading to the release of catecholamines and glucocorticoids (GCs). GCs influence learning and memory by acting on mineralocorticoid (MR) and glucocorticoid (GR) receptors. Typically, GCs enhance the consolidation of memory processing at the same time as impairing the retrieval of memory of emotionally arousing experiences. The present selective review addresses four recent developments in this area. First, the role of the endocannabinoid system in mediating the rapid, nongenomic effects of GCs on memory is illustrated in rodents. Subsequently, studies on the impact of the selective stimulation of MRs on different memory processes in humans are summarised. Next, a series of human experiments on the impact of stress or GC treatment on fear extinction and fear reconsolidation is presented. Finally, the clinical relevance of the effects of exogenous GC administration is highlighted by the description of patients with anxiety disorders who demonstrate an enhancement of extinction-based therapies by GC treatment. The review highlights the substantial progress made in our mechanistic understanding of the memory-modulating properties of GCs, as well as their clinical potential. © 2015 British Society for Neuroendocrinology.

The effect of heat stress on gene expression, synthesis of steroids, and apoptosis in bovine granulosa cells.

PubMed

Li, Lian; Wu, Jie; Luo, Man; Sun, Yu; Wang, Genlin

2016-05-01

Summer heat stress (HS) is a major contributing factor in low fertility in lactating dairy cows in hot environments. Heat stress inhibits ovarian follicular development leading to diminished reproductive efficiency of dairy cows during summer. Ovarian follicle development is a complex process. During follicle development, granulosa cells (GCs) replicate, secrete hormones, and support the growth of the oocyte. To obtain an overview of the effects of heat stress on GCs, digital gene expression profiling was employed to screen and identify differentially expressed genes (DEGs; false discovery rate (FDR) ≤ 0.001, fold change ≥2) of cultured GCs during heat stress. A total of 1211 DEGs including 175 upregulated and 1036 downregulated ones were identified, of which DEGs can be classified into Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results suggested that heat stress triggers a dramatic and complex program of altered gene expression in GCs. We hypothesized that heat stress could induce the apoptosis and dysfunction of GCs. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of steroidogenic genes (steroidogenic acute regulatory protein (Star), cytochrome P-450 (CYP11A1), CYP19A1, and steroidogenic factor 1 (SF-1)) and apoptosis-related genes (caspase-3, BCL-2, and BAX). Radio immunoassay (RIA) was used to analyze the level of 17β-estradiol (E2) and progesterone (P4). We also assessed the apoptosis of GCs by flow cytometry. Our data suggested that heat stress induced GC apoptosis through the BAX/BCL-2 pathway and reduced the steroidogenic gene messenger RNA (mRNA) expression and E2 synthesis. These results suggest that the decreased function of GCs may cause ovarian dysfunction and offer an improved understanding of the molecular mechanism responsible for the low fertility in cattle in summer.

Prohibitin (PHB) inhibits apoptosis in rat granulosa cells (GCs) through the extracellular signal-regulated kinase 1/2 (ERK1/2) and the Bcl family of proteins.

PubMed

Chowdhury, Indrajit; Thompson, Winston E; Welch, Crystal; Thomas, Kelwyn; Matthews, Roland

2013-12-01

Mammalian ovarian follicular development is tightly regulated by crosstalk between cell death and survival signals, which include both endocrine and intra-ovarian regulators. Whether the follicle ultimately ovulates or undergoes atresia is dependent on the expression and actions of factors promoting follicular cell proliferation, differentiation or apoptosis. Prohibitin (PHB) is a highly conserved, ubiquitous protein that is abundantly expressed in granulosa cells (GCs) and associated with GC differentiation and apoptosis. The current study was designed to characterize the regulation of anti-apoptotic and pro-apoptotic factors in undifferentiated rat GCs (gonadotropin independent phase) governed by PHB. Microarray technology was initially employed to identify potential apoptosis-related genes, whose expression levels within GCs were altered by either staurosporine (STS) alone or STS in presence of ectopically over-expressed PHB. Next, immunoblot studies were performed to examine the expression patterns of selective Bcl-2 family members identified by the microarray analysis, which are commonly regulated in the intrinsic-apoptotic pathway. These studies were designed to measure protein levels of Bcl2 family in relation to expression of the acidic isoform (phosphorylated) PHB and the components of MEK-Erk1/2 pathway. These studies indicated that over-expression of PHB in undifferentiated GCs inhibit apoptosis which concomitantly results in an increased level of the anti-apoptotic proteins Bcl2 and Bclxl, reduced release of cytochrome c from mitochondria and inhibition of caspase-3 activity. In contrast, silencing of PHB expression resulted in change of mitochondrial morphology from the regular reticular network to a fragmented form, which enhanced sensitization of these GCs to the induction of apoptosis. Collectively, these studies have provided new insights on the PHB-mediated anti-apoptotic mechanism, which occurs in undifferentiated GCs through a PHB → Mek-Erk1/2 → Bcl/Bcl-xL pathway and may have important clinical implications.

Synthesis and characterization of wollastonite glass-ceramics for dental implant applications.

PubMed

Saadaldin, Selma A; Rizkalla, Amin S

2014-03-01

To synthesize a glass-ceramic (GC) that is suitable for non-metallic one-piece dental implant application. Three glasses in a SiO2-Al2O3-CaO-CaF2-K2O-B2O3-P2O5-CeO2-Y2O3 system were produced by wet chemistry. Differential thermal analysis (DTA) was carried out to determine the glass crystallization kinetic parameters and the heating schedules that were used for sintering of GCs. Crystalline phases and crystal morphologies were studied by X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. Mechanical properties of the GCs were determined by ultrasonic and indentation tests and its machinability were evaluated. Chemical durability was carried out according to ISO 6872, whereas testing chemical degradation in tris buffered solution was executed according to ISO 10993-14. XRD of the GC specimens showed that wollastonite was the main crystalline with other secondary phases; GC2 had cristobalite as an additional phase. SEM of the GCs revealed dense acicular interlocking crystals. Young's modulus of elasticity (E), true hardness (Ho) and fracture toughness (KIC) of the GCs were 89-100GPa, 4.85-5.17GPa and 4.62-5.58MPam(0.5), respectively. All GCs were demonstrated excellent machinability. The GCs exhibited various chemical durability and degradation rates. KIC values of the GCs following chemical durability testing were not significantly different from those of the original materials (p>0.05). GC2 exhibited significantly higher KIC value compared with GC1 and GC3 (p<0.05) and its chemical durability satisfied ISO 6872 specification for dental ceramics. Wollastonite-cristobalite GC can be considered as a promising material for one-piece dental implant applications due to its strength, machinability and chemical durability. Copyright © 2014. Published by Elsevier Ltd.

REVERSED TREND OF RADIAL DISTRIBUTION OF SUBPOPULATIONS IN THE GLOBULAR CLUSTERS NGC 362 AND NGC 6723

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

Lim, Dongwook; Lee, Young-Wook; Pasquato, Mario

2016-12-01

Most globular clusters (GCs) are now known to host multiple stellar populations with different abundances of light elements. Here we use narrow-band photometry and low-resolution spectroscopy for NGC 362 and NGC 6723 to investigate their chemical properties and radial distributions of subpopulations. We confirm that NGC 362 and NGC 6723 are among the GCs with multiple populations showing bimodal CN distribution and CN–CH anticorrelation without a significant spread in calcium abundance. These two GCs show more centrally concentrated CN-weak, earlier generation stars compared to the CN-strong, later generation stars. These trends are reversed with respect to those found in previous studies for many othermore » GCs. Our findings, therefore, seem contradictory to the current scenario for the formation of multiple stellar populations, but mass segregation acting on the two subpopulations might be a possible solution to explain this reversed radial trend.« less

Stress Increases Peripheral Axon Growth and Regeneration through Glucocorticoid Receptor-Dependent Transcriptional Programs

PubMed Central

Alexander, Jessica K.; Madalena, Kathryn M.; Motti, Dario; Quach, Tam; Zha, Alicia; Webster Marketon, Jeanette

2017-01-01

Abstract Stress and glucocorticoid (GC) release are common behavioral and hormonal responses to injury or disease. In the brain, stress/GCs can alter neuron structure and function leading to cognitive impairment. Stress and GCs also exacerbate pain, but whether a corresponding change occurs in structural plasticity of sensory neurons is unknown. Here, we show that in female mice (Mus musculus) basal GC receptor (Nr3c1, also known as GR) expression in dorsal root ganglion (DRG) sensory neurons is 15-fold higher than in neurons in canonical stress-responsive brain regions (M. musculus). In response to stress or GCs, adult DRG neurite growth increases through mechanisms involving GR-dependent gene transcription. In vivo, prior exposure to an acute systemic stress increases peripheral nerve regeneration. These data have broad clinical implications and highlight the importance of stress and GCs as novel behavioral and circulating modifiers of neuronal plasticity. PMID:28828403

Relevance of chronic stress and the two faces of microglia in Parkinson’s disease

PubMed Central

Herrera, Antonio J.; Espinosa-Oliva, Ana M.; Carrillo-Jiménez, Alejandro; Oliva-Martín, María J.; García-Revilla, Juan; García-Quintanilla, Alberto; de Pablos, Rocío M.; Venero, José L.

2015-01-01

This review is aimed to highlight the importance of stress and glucocorticoids (GCs) in modulating the inflammatory response of brain microglia and hence its potential involvement in Parkinson’s disease (PD). The role of inflammation in PD has been reviewed extensively in the literature and it is supposed to play a key role in the course of the disease. Historically, GCs have been strongly associated as anti-inflammatory hormones. However, accumulating evidence from the peripheral and central nervous system have clearly revealed that, under specific conditions, GCs may promote brain inflammation including pro-inflammatory activation of microglia. We have summarized relevant data linking PD, neuroinflamamation and chronic stress. The timing and duration of stress response may be critical for delineating an immune response in the brain thus probably explain the dual role of GCs and/or chronic stress in different animal models of PD. PMID:26321913

Male germ cells support long-term propagation of Zika virus.

PubMed

Robinson, Christopher L; Chong, Angie C N; Ashbrook, Alison W; Jeng, Ginnie; Jin, Julia; Chen, Haiqi; Tang, Elizabeth I; Martin, Laura A; Kim, Rosa S; Kenyon, Reyn M; Do, Eileen; Luna, Joseph M; Saeed, Mohsan; Zeltser, Lori; Ralph, Harold; Dudley, Vanessa L; Goldstein, Marc; Rice, Charles M; Cheng, C Yan; Seandel, Marco; Chen, Shuibing

2018-05-29

Evidence of male-to-female sexual transmission of Zika virus (ZIKV) and viral RNA in semen and sperm months after infection supports a potential role for testicular cells in ZIKV propagation. Here, we demonstrate that germ cells (GCs) are most susceptible to ZIKV. We found that only GCs infected by ZIKV, but not those infected by dengue virus and yellow fever virus, produce high levels of infectious virus. This observation coincides with decreased expression of interferon-stimulated gene Ifi44l in ZIKV-infected GCs, and overexpression of Ifi44l results in reduced ZIKV production. Using primary human testicular tissue, we demonstrate that human GCs are also permissive for ZIKV infection and production. Finally, we identified berberine chloride as a potent inhibitor of ZIKV infection in both murine and human testes. Together, these studies identify a potential cellular source for propagation of ZIKV in testes and a candidate drug for preventing sexual transmission of ZIKV.

The globular cluster-dark matter halo connection

NASA Astrophysics Data System (ADS)

Boylan-Kolchin, Michael

2017-12-01

I present a simple phenomenological model for the observed linear scaling of the stellar mass in old globular clusters (GCs) with z = 0 halo mass in which the stellar mass in GCs scales linearly with progenitor halo mass at z = 6 above a minimum halo mass for GC formation. This model reproduces the observed MGCs-Mhalo relation at z = 0 and results in a prediction for the minimum halo mass at z = 6 required for hosting one GC: Mmin(z = 6) = 1.07 × 109 M⊙. Translated to z = 0, the mean threshold mass is Mhalo(z = 0) ≈ 2 × 1010 M⊙. I explore the observability of GCs in the reionization era and their contribution to cosmic reionization, both of which depend sensitively on the (unknown) ratio of GC birth mass to present-day stellar mass, ξ. Based on current detections of z ≳ 6 objects with M1500<-17, values of ξ > 10 are strongly disfavoured; this, in turn, has potentially important implications for GC formation scenarios. Even for low values of ξ, some observed high-z galaxies may actually be GCs, complicating estimates of reionization-era galaxy ultraviolet luminosity functions and constraints on dark matter models. GCs are likely important reionization sources if 5 ≲ ξ ≲ 10. I also explore predictions for the fraction of accreted versus in situ GCs in the local Universe and for descendants of systems at the halo mass threshold of GC formation (dwarf galaxies). An appealing feature of the model presented here is the ability to make predictions for GC properties based solely on dark matter halo merger trees.

Morphometry of Hilar Ectopic Granule Cells in the Rat

PubMed Central

Pierce, Joseph P.; McCloskey, Daniel P.; Scharfman, Helen E.

2014-01-01

Granule cell (GC) neurogenesis in the dentate gyrus (DG) does not always proceed normally. After severe seizures (e.g., status epilepticus [SE]) and some other conditions, newborn GCs appear in the hilus. Hilar ectopic GCs (EGCs) can potentially provide insight into the effects of abnormal location and seizures on GC development. Additionally, hilar EGCs that develop after SE may contribute to epileptogenesis and cognitive impairments that follow SE. Thus, it is critical to understand how EGCs differ from normal GCs. Relatively little morphometric information is available on EGCs, especially those restricted to the hilus. This study quantitatively analyzed the structural morphology of hilar EGCs from adult male rats several months after pilocarpineinduced SE, when they are considered to have chronic epilepsy. Hilar EGCs were physiologically identified in slices, intracellularly labeled, processed for light microscopic reconstruction, and compared to GC layer GCs, from both the same post-SE tissue and the NeuroMorpho database (normal GCs). Consistently, hilar EGC and GC layer GCs had similar dendritic lengths and field sizes, and identifiable apical dendrites. However, hilar EGC dendrites were topologically more complex, with more branch points and tortuous dendritic paths. Three-dimensional analysis revealed that, remarkably, hilar EGC dendrites often extended along the longitudinal DG axis, suggesting increased capacity for septotemporal integration. Axonal reconstruction demonstrated that hilar EGCs contributed to mossy fiber sprouting. This combination of preserved and aberrant morphological features, potentially supporting convergent afferent input to EGCs and broad, divergent efferent output, could help explain why the hilar EGC population could impair DG function. PMID:21344409

The SLUGGS survey: globular cluster kinematics in a `double sigma' galaxy - NGC 4473

NASA Astrophysics Data System (ADS)

Alabi, Adebusola B.; Foster, Caroline; Forbes, Duncan A.; Romanowsky, Aaron J.; Pastorello, Nicola; Brodie, Jean P.; Spitler, Lee R.; Strader, Jay; Usher, Christopher

2015-09-01

NGC 4473 is a so-called double sigma (2σ) galaxy, i.e. a galaxy with rare, double peaks in its 2D stellar velocity dispersion. Here, we present the globular cluster (GC) kinematics in NGC 4473 out to ˜10Re (effective radii) using data from combined Hubble Space Telescope/Advanced Camera for Surveys and Subaru/Suprime-Cam imaging and Keck/Deep Imaging Multi-Object Spectrograph. We find that the 2σ nature of NGC 4473 persists up to 3Re, though it becomes misaligned to the photometric major axis. We also observe a significant offset between the stellar and GC rotation amplitudes. This offset can be understood as a co-addition of counter-rotating stars producing little net stellar rotation. We identify a sharp radial transition in the GC kinematics at ˜4Re suggesting a well defined kinematically distinct halo. In the inner region (<4Re), the blue GCs rotate along the photometric major axis, but in an opposite direction to the galaxy stars and red GCs. In the outer region (>4Re), the red GCs rotate in an opposite direction compared to the inner region red GCs, along the photometric major axis, while the blue GCs rotate along an axis intermediate between the major and minor photometric axes. We also find a kinematically distinct population of very red GCs in the inner region with elevated rotation amplitude and velocity dispersion. The multiple kinematic components in NGC 4473 highlight the complex formation and evolutionary history of this 2σ galaxy, as well as a distinct transition between the inner and outer components.

Medical geology in the framework of the sustainable development goals.

PubMed

Bundschuh, Jochen; Maity, Jyoti Prakash; Mushtaq, Shahbaz; Vithanage, Meththika; Seneweera, Saman; Schneider, Jerusa; Bhattacharya, Prosun; Khan, Nasreen Islam; Hamawand, Ihsan; Guilherme, Luiz R G; Reardon-Smith, Kathryn; Parvez, Faruque; Morales-Simfors, Nury; Ghaze, Sara; Pudmenzky, Christa; Kouadio, Louis; Chen, Chien-Yen

2017-03-01

Exposure to geogenic contaminants (GCs) such as metal(loid)s, radioactive metals and isotopes as well as transuraniums occurring naturally in geogenic sources (rocks, minerals) can negatively impact on environmental and human health. The GCs are released into the environment by natural biogeochemical processes within the near-surface environments and/or by anthropogenic activities such as mining and hydrocarbon exploitation as well as exploitation of geothermal resources. They can contaminate soil, water, air and biota and subsequently enter the food chain with often serious health impacts which are mostly underestimated and poorly recognized. Global population explosion and economic growth and the associated increase in demand for water, energy, food, and mineral resources result in accelerated release of GCs globally. The emerging science of "medical geology" assesses the complex relationships between geo-environmental factors and their impacts on humans and environments and is related to the majority of the 17 Sustainable Development Goals in the 2030 Agenda of the United Nations for Sustainable Development. In this paper, we identify multiple lines of evidence for the role of GCs in the incidence of diseases with as yet unknown etiology (causation). Integrated medical geology promises a more holistic understanding of the occurrence, mobility, bioavailability, bio-accessibility, exposure and transfer mechanisms of GCs to the food-chain and humans, and the related ecotoxicological impacts and health effects. Scientific evidence based on this approach will support adaptive solutions for prevention, preparedness and response regarding human and environmental health impacts originating from exposure to GCs. Copyright © 2016 Elsevier B.V. All rights reserved.

Intermittent pneumatic compression to prevent venous thromboembolism in patients with high risk of bleeding hospitalized in intensive care units: the CIREA1 randomized trial.

PubMed

Vignon, Philippe; Dequin, Pierre-François; Renault, Anne; Mathonnet, Armelle; Paleiron, Nicolas; Imbert, Audrey; Chatellier, Delphine; Gissot, Valérie; Lhéritier, Gwenaelle; Aboyans, Victor; Prat, Gwenael; Garot, Denis; Boulain, Thierry; Diehl, Jean-Luc; Bressollette, Luc; Delluc, Aurélien; Lacut, Karine

2013-05-01

Venous thromboembolism (VTE) is a frequent and serious problem in intensive care units (ICU). Anticoagulant treatments have demonstrated their efficacy in preventing VTE. However, when the bleeding risk is high, they are contraindicated, and mechanical devices are recommended. To date, mechanical prophylaxis has not been rigorously evaluated in any trials in ICU patients. In this multicenter, open-label, randomized trial with blinded evaluation of endpoints, we randomly assigned 407 patients with a high risk of bleeding to receive intermittent pneumatic compression (IPC) associated with graduated compression stockings (GCS) or GCS alone for 6 days during their ICU stay. The primary endpoint was the occurrence of a VTE between days 1 and 6, including nonfatal symptomatic documented VTE, or death due to a pulmonary embolism, or asymptomatic deep vein thrombosis detected by ultrasonography systematically performed on day 6. The primary outcome was assessed in 363 patients (89.2%). By day 6, the incidence of the primary outcome was 5.6% (10 of 179 patients) in the IPC + GCS group and 9.2% (17 of 184 patients) in the GCS group (relative risk 0.60; 95% confidence interval 0.28-1.28; p = 0.19). Tolerance of IPC was poor in only 12 patients (6.0%). No intergroup difference in mortality rate was observed. With the limitation of a low statistical power, our results do not support the superiority of the combination of IPC + GCS compared to GCS alone to prevent VTE in ICU patients at high risk of bleeding.

Serum neuron-specific enolase as an early predictor of delayed neuropsychiatric sequelae in patients with acute carbon monoxide poisoning.

PubMed

Cha, Y S; Kim, H; Do, H H; Kim, H I; Kim, O H; Cha, K-C; Lee, K H; Hwang, S O

2018-03-01

Delayed onset of neuropsychiatric symptoms after apparent recovery from acute carbon monoxide (CO) poisoning has been described as delayed neuropsychiatric sequelae (DNS). To date, there have been no studies on the utility of serum neuron-specific enolase (NSE), a marker of neuronal cell damage, as a predictive marker of DNS in acute CO poisoning. This retrospective observational study was performed on adult patients with acute CO poisoning consecutively treated over a 9-month period. Serum NSE was measured after emergency department arrival, and patients were divided into two groups. The DNS group comprised patients with delayed sequelae, while the non-DNS group included patients with none of these sequelae. A total of 98 patients with acute CO poisoning were enrolled in this study. DNS developed in eight patients. The median NSE value was significantly higher in the DNS group than in the non-DNS group. There was a statistical difference between the non-DNS group and the DNS group in terms of CO exposure time, Glasgow Coma Scale (GCS), loss of consciousness, creatinine kinase, and troponin I. GCS and NSE were the early predictors of development of DNS. The area under the curve according to the receiver operating characteristic curves of GCS, serum NSE, and GCS combined with serum NSE were 0.922, 0.836, and 0.969, respectively. In conclusion, initial GCS and NSE served as early predictors of development of DNS. Also, NSE might be a useful additional parameter that could improve the prediction accuracy of initial GCS.

Imaging and quantifying ganglion cells and other transparent neurons in the living human retina.

PubMed

Liu, Zhuolin; Kurokawa, Kazuhiro; Zhang, Furu; Lee, John J; Miller, Donald T

2017-11-28

Ganglion cells (GCs) are fundamental to retinal neural circuitry, processing photoreceptor signals for transmission to the brain via their axons. However, much remains unknown about their role in vision and their vulnerability to disease leading to blindness. A major bottleneck has been our inability to observe GCs and their degeneration in the living human eye. Despite two decades of development of optical technologies to image cells in the living human retina, GCs remain elusive due to their high optical translucency. Failure of conventional imaging-using predominately singly scattered light-to reveal GCs has led to a focus on multiply-scattered, fluorescence, two-photon, and phase imaging techniques to enhance GC contrast. Here, we show that singly scattered light actually carries substantial information that reveals GC somas, axons, and other retinal neurons and permits their quantitative analysis. We perform morphometry on GC layer somas, including projection of GCs onto photoreceptors and identification of the primary GC subtypes, even beneath nerve fibers. We obtained singly scattered images by: ( i ) marrying adaptive optics to optical coherence tomography to avoid optical blurring of the eye; ( ii ) performing 3D subcellular image registration to avoid motion blur; and ( iii ) using organelle motility inside somas as an intrinsic contrast agent. Moreover, through-focus imaging offers the potential to spatially map individual GCs to underlying amacrine, bipolar, horizontal, photoreceptor, and retinal pigment epithelium cells, thus exposing the anatomical substrate for neural processing of visual information. This imaging modality is also a tool for improving clinical diagnosis and assessing treatment of retinal disease. Copyright © 2017 the Author(s). Published by PNAS.

Corruption of the dentate gyrus by "dominant" granule cells: Implications for dentate gyrus function in health and disease.

PubMed

Scharfman, Helen E; Myers, Catherine E

2016-03-01

The dentate gyrus (DG) and area CA3 of the hippocampus are highly organized lamellar structures which have been implicated in specific cognitive functions such as pattern separation and pattern completion. Here we describe how the anatomical organization and physiology of the DG and CA3 are consistent with structures that perform pattern separation and completion. We then raise a new idea related to the complex circuitry of the DG and CA3 where CA3 pyramidal cell 'backprojections' play a potentially important role in the sparse firing of granule cells (GCs), considered important in pattern separation. We also propose that GC axons, the mossy fibers, already known for their highly specialized structure, have a dynamic function that imparts variance--'mossy fiber variance'--which is important to pattern separation and completion. Computational modeling is used to show that when a subset of GCs become 'dominant,' one consequence is loss of variance in the activity of mossy fiber axons and a reduction in pattern separation and completion in the model. Empirical data are then provided using an example of 'dominant' GCs--subsets of GCs that develop abnormally and have increased excitability. Notably, these abnormal GCs have been identified in animal models of disease where DG-dependent behaviors are impaired. Together these data provide insight into pattern separation and completion, and suggest that behavioral impairment could arise from dominance of a subset of GCs in the DG-CA3 network. Copyright © 2015 Elsevier Inc. All rights reserved.

Green tea extract with polyethylene glycol-3350 reduces body weight and improves glucose tolerance in db/db and high-fat diet mice.

PubMed

Park, Jae-Hyung; Choi, Yoon Jung; Kim, Yong Woon; Kim, Sang Pyo; Cho, Ho-Chan; Ahn, Shinbyoung; Bae, Ki-Cheor; Im, Seung-Soon; Bae, Jae-Hoon; Song, Dae-Kyu

2013-08-01

Green tea extract (GTE) is regarded to be effective against obesity and type 2 diabetes, but definitive evidences have not been proven. Based on the assumption that the gallated catechins (GCs) in GTE attenuate intestinal glucose and lipid absorption, while enhancing insulin resistance when GCs are present in the circulation through inhibiting cellular glucose uptake in various tissues, this study attempted to block the intestinal absorption of GCs and prolong their residence time in the lumen. We then observed whether GTE containing the nonabsorbable GCs could ameliorate body weight (BW) gain and glucose intolerance in db/db and high-fat diet mice. Inhibition of the intestinal absorption of GCs was accomplished by co-administering the nontoxic polymer polyethylene glycol-3350 (PEG). C57BLKS/J db/db and high-fat diet C57BL/6 mice were treated for 4 weeks with drugs as follows: GTE, PEG, GTE+PEG, voglibose, or pioglitazone. GTE mixed with meals did not have any ameliorating effects on BW gain and glucose intolerance. However, the administration of GTE plus PEG significantly reduced BW gain, insulin resistance, and glucose intolerance, without affecting food intake and appetite. The effect was comparable to the effects of an α-glucosidase inhibitor and a peroxisome proliferator-activated receptor-γ/α agonist. These results indicate that prolonging the action of GCs of GTE in the intestinal lumen and blocking their entry into the circulation may allow GTE to be used as a prevention and treatment for both obesity and obesity-induced type 2 diabetes.

EBV+ and MSI Gastric Cancers Harbor High PD-L1/PD-1 Expression and High CD8+ Intratumoral Lymphocytes

PubMed Central

De Rosa, Simona; Tibiletti, Maria Grazia; Magnoli, Francesca; Vanoli, Alessandro; Sessa, Fausto; Chiaravalli, Anna Maria

2018-01-01

Both EBV+ and MSI gastric cancers (GCs) have high lymphoid infiltration which is rare in MSS/EBV− cancers. PD-L1/PD-1 interaction leads to a down-regulated immune response and it is one of the most promising targets for gastric cancer immunotherapy. PD-L1/PD-1 and CD8 expression were immunohistochemically investigated in a series of 169 FFPE GCs, including 33 EBV+, 59 MSI and 77 MSS/EBV− cases. PD-L1 membrane immunoreactivity in more than 5% of tumor cells was present in 31/169 GCs and was associated with high levels of CD8 intraepithelial lymphocytes (TILs; p < 0.001). PD-L1+ cases were mainly poorly differentiated (71%), intestinal type (85%) and high lymphoid response (HLR; 90%) tumors. PD-L1 expression was only present in EBV⁺ (46%), MSI (24%) and rare MSS/EBV− (3%) GCs with high CD8+ TILs (p < 0.001). Despite being associated with a better prognosis both in the whole series (p < 0.05) and in the MSI subset, PD-L1 is not an independent prognostic factor. PD-L1 gene amplification was detected in 3/17 cases, including 2/7 EBV+ and 1/8 MSI GC. PD-1⁺ TILs were significantly higher in EBV⁺ than MSI and MSS/EBV− cases. PD-L1/PD-1 pathway is selectively activated in HLR GCs and could be considered an emerging therapeutic target, particularly for EBV and MSI GCs. PMID:29614789

An Investigation of Multiple Unmanned Aircraft Systems Control from the Cockpit of an AH-64 Apache Helicopter

DTIC Science & Technology

2014-12-01

An Investigation of Multiple Unmanned Aircraft Systems Control from the Cockpit of an AH-64 Apache Helicopter by Jamison S Hicks and David B...estimate or any other aspect of this collection of information, including suggestions for reducing the burden, to Department of Defense , Washington...infantrymen, aircraft pilots, or dedicated UAS ground control station (GCS) operators. The purpose of the UAS is to allow for longer and more discrete

Association between expression of cumulus expansion markers and real-time proliferation of porcine follicular granulosa cells in a primary cell culture model.

PubMed

Ciesiółka, S; Budna, J; Bryja, A; Kranc, W; Chachuła, A; Dyszkiewicz-Konwińska, M; Piotrowska, H; Bukowska, D; Antosik, P; Bruska, M; Brüssow, K P; Nowicki, M; Zabel, M; Kempisty, B

2016-01-01

Folliculogenesis is a compound process that involves both ovarian follicle growth and oocyte development, which is tightly attached to the follicular wall. During this process, cells that form the follicle structure undergo substantial morphological and molecular modifications that finally lead to differentiation and specialization of ovarian follicular cells. The differentiation of ovarian cells encompasses formation of follicle, which is composed of theca (TCs), mural granulosa (GCs), and cumulus cells (CCs). It was previously hypothesized that GCs and CCs represent undifferentiated and highly specialized follicular cells, respectively, which may have similar primordial cell origins. In this study, we investigated the expression pattern of cumulus expansion markers such as COX2, HAS2, PTX3, and TSG6 in porcine GCs during short-term, in vitro culture. We hypothesized that these genes may display an important function in GCs in relation to cellular real-time proliferation. The expression pattern of COX2, HAS2, PTX3, and TSG6 was evaluated after using RT-qPCR in relation to confocal microscopy observations of protein expression and distribution during real-time proliferation of porcine follicular GCs. The COX2 and HAS2 mRNAs were highly expressed after 120 h of in vitro culture (IVC), whereas PTX3 and TSG6 mRNAs were increased during the first 24-48 h of IVC (P less than 0.001, P less than 0.01). Conversely, all of the encoded proteins were highly expressed after 144-168 h of IVC as compared to other culture periods (P less than 0.001, P less than 0.01). When analyzing the realtime proliferation of GCs in vitro, we observed a logarithmic increase of cell proliferation between 0 h and 120 h of IVC. However, after 120-168 h of IVC, the cells reached the lag phase of proliferation. Since it is well accepted that porcine GCs undergo luteinization shortly after 24-48 h of IVC, the expression pattern of investigated genes indicated that Cox2 and Has2 are independent from the LH surge, but their increased levels may be upregulated by cell proliferation in vitro. Moreover, higher expression of PTX3 and TSG6 during first 24 h and/or 48 h of IVC suggested that their levels are accompanied by porcine GCs luteinization process.

Optimal Timing of Oceanic, Geological and Biological Carbon Sequestration to Safeguard Climate

NASA Astrophysics Data System (ADS)

Gitz, V.; Ambrosi, P.; Ciais, P.; Orr, J.; Magne, B.; Hourcade, J.

2005-12-01

We address the issue of safeguarding climate in the presence of a cascade of uncertainties through a portfolio of mitigation options: emissions reductions (M), biological carbon sequestration (BCS), carbon capture and storage - both geological (GCS) and oceanic (OCS). Within a sequential decision framework (i.e. as uncertainties are progressively resolved with time), we use a global optimal control model, RESPONSE, to examine the relative advantages of the three sequestration options in lowering fossil fuel abatement expenditures. Moreover, we show to what extent these options offer additional flexibility for short- and long-term decision given uncertainties on climate sensitivity and ``safe'' climate targets. To do so, we compute the value of information regarding these uncertainties and assess the timeliness of learning (i.e. which uncertainty is more``urgent'' to resolve). Finally, we show to what extent short term optimal paths of fossil emissions abatement and carbon sequestration are robust to these uncertainties. We find that BCS, GCS and OCS are complementary both in alleviating the constraint on the energy sector and in tackling the uncertainties. BCS is used more in the short term as a brake whereas OCS and GCS are used more in the long term as a safety valve. In other words, a portfolio approach is preferable to an approach based solely on emissions reduction: with a fully- diversified mitigation portfolio, discounted global climate policy costs are up to 38% lower than with an abatement-only policy and discounted abatement costs decrease up to 54%. Short-term costs are lower, mainly (81%) thanks to BCS - a result relatively independent upon the emissions scenario. Long- term costs are mainly lower thanks to GCS or OCS, both options being concurrent. However, in the case of high-emissions scenarios (like A2), OCS proves highly helpful (up to 25% of A2 reference scenario cumulated emissions could be stored). Though marginal in duration given the opportunity cost to permanently immobilize lands, BCS proves helpful on short-term (when the rate constraint essentially bites) against all uncertainties. GCS and OCS, which deploy later and prove helpful against uncertainties that are pregnant on a longer term (like the magnitude constraint), or when they are supposed to be resolved in the long run. \\begin{tabular}{ccccccc}\\hline\\hline &μlticolumn{3}{c} {early learning}&μlticolumn{3}{c}{late learning} policy option&t2x&ryt&tmax&t2x&ryt&tmax\\hline M&1.64&6.32&1.24&2.22&7.81&4.46 M+BCS&1.05&4.44&0.84&1.50&5.55&3.29 M+GCS&1.51&5.91&0.80&2.02&6.90&2.47 M+OCS&1.62&6.02&0.89&2.13&6.93&2.47 M+BCS+GCS+OCS&1.02&4.22&0.59&1.45&5.07&2.04\\hline\\hline Table 1. The value of information in 1990 (T US90$) for the climate sensitivity (t2x), the rate constraint (ryt), the magnitude constraint (tmax) in early-learning (2030) and late-learning (2060) scenarios, under four policy options.53 wt.

Management issues with exogenous steroid therapy

PubMed Central

Patt, Hiren; Bandgar, Tushar; Lila, Anurag; Shah, Nalini

2013-01-01

Glucocorticoids (GCs) are extensively used for various inflammatory and autoimmune disorders, but long term use of these agents is not without complications. Almost every GC formulations (e.g. oral, topical, inhaled, etc.) can cause systemic side effects. It can range from minor side effects (e.g. weight gain) to life-threatening effects (e.g. adrenal suppression, sepsis, etc.), which may require immediate intervention. Therefore, the decision to institute steroid therapy always requires careful consideration of the relative risk and benefit in each patient. The objectives of this study are to discuss monitoring of patients on GCs and management of the complications of GCs. PMID:24910822

The 90-day prognostic value of serum cyclophilin A in traumatic brain injury.

PubMed

Jin, Hang-Huang; Mao, Tian-Ming; Bai, Zhi-Qiang; Chen, Yuan; Ji, Hai-Long; Jin, Yong

2018-06-07

Cyclophilin A is involved in many inflammatory diseases and its expression is up-regulated after brain injury. We determined if serum cyclophilin A could be used as a marker for severity and 90-day outcome in patients with traumatic brain injury (TBI). Serum cyclophilin A concentrations were quantified in 105 severe TBI patients and 105 healthy individuals. Its association with Glasgow Coma Scale (GCS) score, 90-day mortality and 90-day poor outcome (Glasgow Outcome Scale score of 1-3) were investigated. Serum cyclophilin A concentrations were significantly higher in TBI patients than in healthy individuals. Cyclophilin A concentrations had a close relation to GCS scores and showed a high discriminatory ability for 90-day mortality and poor outcome according to area under receiver operating characteristic curve (AUC). Its AUC was in the range of GCS scores. Moreover, its combination with GCS scores significantly improved the predictive performance of GCS scores alone. In addition, serum cyclophilin A emerged as an independent predictor for 90-day mortality, overall survival and poor outcome. Increased serum cyclophilin A concentrations could reflect trauma severity and unfavorable outcome after head trauma, substantializing cyclophilin A as a potential biomarker for prognostic prediction of TBI. Copyright © 2018 Elsevier B.V. All rights reserved.

The correlation between the sizes of globular cluster systems and their host dark matter haloes

NASA Astrophysics Data System (ADS)

Hudson, Michael J.; Robison, Bailey

2018-07-01

The sizes of entire systems of globular clusters (GCs) depend not only on the formation and destruction histories of the GCs themselves but also on the assembly, merger, and accretion history of the dark matter (DM) haloes that they inhabit. Recent work has shown a linear relation between total mass of GCs in the GC system and the mass of its host DM halo, calibrated from weak lensing. Here, we extend this to GC system sizes, by studying the radial density profiles of GCs around galaxies in nearby galaxy groups. We find that radial density profiles of the GC systems are well fit with a de Vaucouleurs profile. Combining our results with those from the literature, we find tight relationship (˜0.2 dex scatter) between the effective radius of the GC system and the virial radius (or mass) of its host DM halo, for haloes with masses greater than ˜1012 M⊙. The steep non-linear dependence of this relationship (R_{ {e, GCS}} ∝ R_{200}^{2.5 - 3} ∝ M_{200}^{0.8 - 1}) is currently not well understood, but is an important clue regarding the assembly history of DM haloes and of the GC systems that they host.

Improvement in GOS and GOSE scores 6 and 12 months after severe traumatic brain injury.

PubMed

Corral, Luisa; Ventura, José Luis; Herrero, José Ignacio; Monfort, Jose Luis; Juncadella, Montserrat; Gabarrós, Andreu; Bartolomé, Carlos; Javierre, Casimiro F; García-Huete, Lucía

2007-11-01

To assess improvements in Glasgow Outcome Scale (GOS) and GOS extended (GOSE) scores between 6 months and 1 year following severe traumatic brain injury (TBI). One studied 214 adult patients with severe TBI with Glasgow Coma Scale (GCS) <9 admitted to Intensive Care Unit (ICU). GOS scores were obtained 6 and 12 months after injury in 195 subjects. Patients were predominantly male (84%) and median age was 35 years. Outcome (GOS and GOSE at 6 months and 1 year) was better in the high GCS score at admission (6-8) group than in the low score group (3-5). The improvement in GOS scores between 6 months and 1 year was greater in the high GCS score at admission group than in the low score group. At 6 months, 75 patients had died and 120 survived. None died between the 6-12-month assessments; at 12 months, 36% had improved GOS score. GOS scores improved between 6-12 months after severe TBI in 36% of survivors and it is concluded that the expectancy of improvement is incomplete at 6 months. This improvement was greater in patients with better GCS scores (6-8) at admission than in those with worse GCS scores (3-5).

The relation between persistent coma and brain ischemia after severe brain injury.

PubMed

Cheng, Quan; Jiang, Bing; Xi, Jian; Li, Zhen Yan; Liu, Jin Fang; Wang, Jun Yu

2013-12-01

To investigate the relation between brain ischemia and persistent vegetative state after severe traumatic brain injury. The 66 patients with severe brain injury were divided into two groups: The persistent coma group (coma duration ≥10 d) included 51 patients who had an admission Glasgow Coma Scale (GCS) of 5-8 and were unconscious for more than 10 d. There were 15 patients in the control group, their admission GCS was 5-8, and were unconscious for less than 10 d. The brain areas, including frontal, parietal, temporal, occipital lobes and thalamus, were measured by Single Photon Emission Computed Tomography (SPECT). In the first SPECT scan, multiple areas of cerebral ischemia were documented in all patients in both groups, whereas bilateral thalamic ischemia were presented in all patients in the persistent coma group and were absented in the control group. In the second SPECT scan taken during the period of analepsia, with an indication that unilateral thalamic ischemia were persisted in 28 of 41 patients in persistent coma group(28/41,68.29%). Persistent coma after severe brain injury is associated with bilateral thalamic ischemia.

Vitamin D Alters Genes Involved in Follicular Development and Steroidogenesis in Human Cumulus Granulosa Cells

PubMed Central

Doswell, Angela; Krebs, Kendall; Cipolla, Marilyn

2014-01-01

Context: Vitamin D deficiency is common among reproductive-aged women and has a role in female reproduction. Objective: This study evaluated the role of 1,25-dihydroxyvitamin D3 (vit D3) in ovarian follicular development and steroidogenesis by using a human granulosa cell (GC) model. Design, Setting, and Participants: Fifty-four women who underwent in vitro fertilization were enrolled. Intervention: Follicular fluid (FF) and mural and cumulus GCs were collected from small and large follicles. In separate experiments, primary cumulus GCs were cultured with or without vit D3 followed by RT-PCR for mRNA expression levels. The effect of recombinant anti-Mullerian hormone (AMH) on nuclear localization of phospho-Smad 1/5/8 was evaluated in the presence or absence of vit D3 by using immunofluorescence. 25-Hydroxyvitamin D levels in FF as well as cell culture media AMH, progesterone, and estradiol (E2) concentrations were determined by ELISA and RIA. Main Outcome Measures: The following were measured: 1) mRNA expression levels; 2) 3β-hydroxysteroid dehydrogenase (3β-HSD) enzyme activity; 3) FSH-induced aromatase mRNA and E2 production; and 4) nuclear localization of phospho-Smad 1/5/8. Results: In a multivariate analysis, 25 OH-D levels in FF negatively correlated with AMH and AMH receptor (AMHR)-II mRNA levels in cumulus GCs of small follicles. Compared with women with replete 25-hydroxyvitamin D levels in FF, those with insufficient/deficient levels had a 2-fold increase in AMHR-II mRNA levels in cumulus GCs of small follicles (P = .02). Treatment with vit D3 caused a decrease in AMHR-II and FSH receptor mRNA but an increase in 3-βHSD mRNA levels compared with control (P < .05). Vit D3 enhanced 3-βHSD enzyme activity as assessed by increasing progesterone release; however, vit D3 did not affect FSH-induced aromatase mRNA and E2 production, but it decreased the phosphorylation of Smad 1/5/8 and its nuclear localization. Conclusion: These data suggest that vit D3 alters AMH signaling and steroidogenesis in human cumulus GCs, possibly reflecting a state of GC luteinization potentiation. PMID:24628555

Phosphoinositide 3-Kinase p110δ Mediates Estrogen- and FSH-Stimulated Ovarian Follicle Growth

PubMed Central

Li, Qian; He, Hui; Zhang, Yin-Li; Li, Xiao-Meng; Guo, Xuejiang; Huo, Ran; Bi, Ye; Li, Jing

2013-01-01

In the mammalian ovary, primordial follicles are generated early in life and remain dormant for prolonged periods. Their growth resumes via primordial follicle activation, and they continue to grow until the preovulatory stage under the regulation of hormones and growth factors, such as estrogen, FSH, and IGF-1. Both FSH and IGF-1 activate the phosphatidylinositol-3 kinase (PI3K)/Akt (acute transforming retrovirus thymoma protein kinase) signaling pathway in granulosa cells (GCs), yet it remains inconclusive whether the PI3K pathway is crucial for follicle growth. In this study, we investigated the p110δ isoform (encoded by the Pik3cd gene) of PI3K catalytic subunit expression in the mouse ovary and its function in fertility. Pik3cd-null females were subfertile, exhibited fewer growing follicles and more atretic antral follicles in the ovary, and responded poorly to exogenous gonadotropins compared with controls. Ovary transplantation showed that Pik3cd-null ovaries responded poorly to FSH stimulation in vitro; this confirmed that the follicle growth defect was intrinsically ovarian. In addition, estradiol (E2)-stimulated follicle growth and GC proliferation in preantral follicles was impaired in Pik3cd-null ovaries. FSH and E2 substantially activated the PI3K/Akt pathway in GCs of control mice but not in those of Pik3cd-null mice. However, primordial follicle activation and oocyte meiotic maturation were not affected by Pik3cd knockout. Taken together, our findings indicate that the p110δ isoform of the PI3K catalytic subunit is a key component of the PI3K pathway for both FSH and E2-stimulated follicle growth in ovarian GCs; however, it is not required for primordial follicle activation and oocyte development. PMID:23820902

Long-term consequences of a short-term hypergravity load in a snail model

NASA Astrophysics Data System (ADS)

Martynova, Marina G.; Shabelnikov, Sergej V.; Bystrova, Olga A.

2015-07-01

Here we focused on the dynamic processes in the snail at different time after short-term hypergravity load (STHL) by monitoring the state of neuroendocrine and immune systems, the nucleic acid synthesis levels in the atrial cells, and the behaviour of the atrial granular cells (GCs). We observed that immediately after centrifugation (14 g for 15 min) in the snail haemolymph concentration of dopamine and noradrenaline (measured by high-performance liquid chromatography) and the number of circulating haemocytes and their proliferative activity (estimated by the direct cell counting and [3H]thymidine incorporation, respectively) increased significantly, whereas the concentration of adrenaline decreased. Twenty-four hours after STHL, the levels of catecholamines and haemocytes returned to their control values. In the atrial epicardial and endothelial cells, a notable drop of transcription activity (evaluated by [3H]uridine autoradiography) from the baseline in the immediate post-STHL period was followed by its gradual increase reaching a maximum at the day 5 and subsequent decrease to control value by the day 10. In endothelial cells, DNA-synthesizing activity (evaluated by [3H]thymidine autoradiography) equal to zero before and just after STHL, increased significantly at the day 5, and decreased by the day 10. The atrial GCs underwent total degranulation. Formed as a result small ungranulated cells exhibited DNA synthesis. Afterwards, most probably, the GCs divided and regranulated. One month after STHL the GC population had been restored. Overall, STHL has triggered an immediate reaction of the neuroendocrine and immune systems and initiated long-lasting processes at a cellular level, which included alterations in activity of nucleic acid syntheses in the epicardial and endothelial cells and remodelling of the GC population in the atrium.

Analysis of long-term (median 10.5 years) outcomes in children presenting with traumatic brain injury and an initial Glasgow Coma Scale score of 3 or 4.

PubMed

Fulkerson, Daniel H; White, Ian K; Rees, Jacqueline M; Baumanis, Maraya M; Smith, Jodi L; Ackerman, Laurie L; Boaz, Joel C; Luerssen, Thomas G

2015-10-01

Patients with traumatic brain injury (TBI) with low presenting Glasgow Coma Scale (GCS) scores have very high morbidity and mortality rates. Neurosurgeons may be faced with difficult decisions in managing the most severely injured (GCS scores of 3 or 4) patients. The situation may be considered hopeless, with little chance of a functional recovery. Long-term data are limited regarding the clinical outcome of children with severe head injury. The authors evaluate predictor variables and the clinical outcomes at discharge, 1 year, and long term (median 10.5 years) in a cohort of children with TBI presenting with postresuscitation GCS scores of 3 and 4. A review of a prospectively collected trauma database was performed. Patients treated at Riley Hospital for Children (Indianapolis, Indiana) from 1988 to 2004 were reviewed. All children with initial GCS (modified for pediatric patients) scores of 3 or 4 were identified. Patients with a GCS score of 3 were compared with those with a GCS score of 4. The outcomes of all patients at the time of death or discharge and at 1-year and long-term follow-up were measured with a modified Glasgow Outcome Scale (GOS) that included a "normal" outcome. Long-term outcomes were evaluated by contacting surviving patients. Statistical "classification trees" were formed for survival and outcome, based on predictor variables. Sixty-seven patients with a GCS score of 3 or 4 were identified in a database of 1636 patients (4.1%). Three of the presenting factors differed between the GCS 3 patients (n = 44) and the GCS 4 patients (n = 23): presence of hypoxia, single seizure, and open basilar cisterns on CT scan. The clinical outcomes were statistically similar between the 2 groups. In total, 48 (71.6%) of 67 patients died, remained vegetative, or were severely disabled by 1 year. Eight patients (11.9%) were normal at 1 year. Ten of the 22 patients with long-term follow-up were either normal or had a GOS score of 5. Multiple clinical, historical, and radiological factors were analyzed for correlation with survival and clinical outcome. Classification trees were formed to stratify predictive factors. The pupillary response was the factor most predictive of both survival and outcome. Other factors that either positively or negatively correlated with survival included hypothermia, mechanism of injury (abuse), hypotension, major concurrent symptoms, and midline shift on CT scan. Other factors that either positively or negatively predicted long-term outcome included hypothermia, mechanism of injury, and the assessment of the fontanelle. In this cohort of 67 TBI patients with a presenting GCS score of 3 or 4, 56.6% died within 1 year. However, approximately 15% of patients had a good outcome at 10 or more years. Factors that correlated with survival and outcome included the pupillary response, hypothermia, and mechanism. The authors discuss factors that may help surgeons make critical decisions regarding their most serious pediatric trauma patients.

How Do Health Care Providers Diagnose Traumatic Brain Injury (TBI)?

MedlinePlus

... correlation between initial GCS score and the person's short- or long-term recovery or abilities. 2 Measurements for Level of TBI Health care providers sometimes rank the person's level of consciousness, memory loss, and GCS score. A TBI is considered ...

Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer’s Disease

PubMed Central

Sun, Binggui; Halabisky, Brian; Zhou, Yungui; Palop, Jorge J.; Yu, Guiqiu; Mucke, Lennart; Gan, Li

2009-01-01

SUMMARY Adult neurogenesis regulates plasticity and function in the hippocampus, which is critical for memory and vulnerable to Alzheimer’s disease (AD). Promoting neurogenesis may improve hippocampal function in AD brains. However, how amyloid β (Aβ), the key AD pathogen, affects the development and function of adult-born neurons remains unknown. Adult-born granule cells (GCs) in human amyloid precursor protein (hAPP) transgenic mice, an AD model, showed greater dendritic length, spine density, and functional responses than controls early in development, but were impaired morphologically and functionally during later maturation. Early inhibition of GABAA receptors to suppress GABAergic signaling or late inhibition of calcineurin to enhance glutamatergic signaling normalized the development of adult-born GCs in hAPP mice with high Aβ levels. Aβ-induced increases in GABAergic neurotransmission or an imbalance between GABAergic and glutamatergic neurotransmission may contribute to impaired neurogenesis in AD. PMID:19951690

Neuronal expression of glucosylceramide synthase in central nervous system regulates body weight and energy homeostasis.

PubMed

Nordström, Viola; Willershäuser, Monja; Herzer, Silke; Rozman, Jan; von Bohlen Und Halbach, Oliver; Meldner, Sascha; Rothermel, Ulrike; Kaden, Sylvia; Roth, Fabian C; Waldeck, Clemens; Gretz, Norbert; de Angelis, Martin Hrabě; Draguhn, Andreas; Klingenspor, Martin; Gröne, Hermann-Josef; Jennemann, Richard

2013-01-01

Hypothalamic neurons are main regulators of energy homeostasis. Neuronal function essentially depends on plasma membrane-located gangliosides. The present work demonstrates that hypothalamic integration of metabolic signals requires neuronal expression of glucosylceramide synthase (GCS; UDP-glucose:ceramide glucosyltransferase). As a major mechanism of central nervous system (CNS) metabolic control, we demonstrate that GCS-derived gangliosides interacting with leptin receptors (ObR) in the neuronal membrane modulate leptin-stimulated formation of signaling metabolites in hypothalamic neurons. Furthermore, ganglioside-depleted hypothalamic neurons fail to adapt their activity (c-Fos) in response to alterations in peripheral energy signals. Consequently, mice with inducible forebrain neuron-specific deletion of the UDP-glucose:ceramide glucosyltransferase gene (Ugcg) display obesity, hypothermia, and lower sympathetic activity. Recombinant adeno-associated virus (rAAV)-mediated Ugcg delivery to the arcuate nucleus (Arc) significantly ameliorated obesity, specifying gangliosides as seminal components for hypothalamic regulation of body energy homeostasis.

AGB subpopulations in the nearby globular cluster NGC 6397

NASA Astrophysics Data System (ADS)

MacLean, B. T.; Campbell, S. W.; De Silva, G. M.; Lattanzio, J.; D'Orazi, V.; Cottrell, P. L.; Momany, Y.; Casagrande, L.

2018-03-01

It has been well established that Galactic Globular clusters (GCs) harbour more than one stellar population, distinguishable by the anticorrelations of light-element abundances (C-N, Na-O, and Mg-Al). These studies have been extended recently to the asymptotic giant branch (AGB). Here, we investigate the AGB of NGC 6397 for the first time. We have performed an abundance analysis of high-resolution spectra of 47 red giant branch (RGB) and eight AGB stars, deriving Fe, Na, O, Mg, and Al abundances. We find that NGC 6397 shows no evidence of a deficit in Na-rich AGB stars, as reported for some other GCs - the subpopulation ratios of the AGB and RGB in NGC 6397 are identical, within uncertainties. This agrees with expectations from stellar theory. This GC acts as a control for our earlier work on the AGB of M4 (with contrasting results), since the same tools and methods were used.

Ikhana: A NASA UAS Supporting Long Duration Earth Science Missions

NASA Technical Reports Server (NTRS)

Cobleigh, Brent R.

2007-01-01

The NASA Ikhana unmanned aerial vehicle (UAV) is a General Atomics Aeronautical Systems Inc. (San Diego, California) MQ-9 Predator-B modified to support the conduct of Earth science missions for the NASA Science Mission Directorate and, through partnerships, other government agencies and universities. It can carry over 2000 lb of experiment payloads in the avionics bay and external pods and is capable of mission durations in excess of 24 hours at altitudes above 40,000 ft. The aircraft is remotely piloted from a mobile ground control station (GCS) that is designed to be deployable by air, land, or sea. On-board support capabilities include an instrumentation system and an Airborne Research Test System (ARTS). The Ikhana project will complete GCS development, science support systems integration, external pod integration and flight clearance, and operations crew training in early 2007. A large-area remote sensing mission is currently scheduled for Summer 2007.

Performance of Glial Fibrillary Acidic Protein (GFAP) in Detecting Traumatic Intracranial Lesions on Computed Tomography in Children and Youth with Mild Head Trauma

PubMed Central

Papa, Linda; Zonfrillo, Mark; Ramirez, Jose; Silvestri, Salvatore; Giordano, Philip; Braga, Carolina F.; Tan, Ciara N.; Ameli, Neema J.; Lopez, Marco; Mittal, Manoj K.

2015-01-01

Objectives This study examined the performance of serum glial fibrillary acidic protein (GFAP) in detecting traumatic intracranial lesions on computed tomography (CT) scan in children and youth with mild and moderate traumatic brain injury (TBI), and assessed its performance in trauma control patients without head trauma. Methods This prospective cohort study enrolled children and youth presenting to three Level I trauma centers following blunt head trauma with Glasgow Coma Scale (GCS) scores of 9 to 15, as well as trauma control patients with GCS scores of 15 who did not have blunt head trauma. The primary outcome measure was the presence of intracranial lesions on initial CT scan. Blood samples were obtained in all patients within six hours of injury and measured by ELISA for GFAP (ng/ml). Results A total of 257 children and youth were enrolled in the study and had serum samples drawn within 6 hours of injury for analysis: 197 had blunt head trauma and 60 were trauma controls. CT scan of the head was performed in 152 patients and traumatic intracranial lesions on CT scan were evident in 18 (11%), all of whom had GCS scores of 13 to 15. When serum levels of GFAP were compared in children and youth with traumatic intracranial lesions on CT scan to those without CT lesions, median GFAP levels were significantly higher in those with intracranial lesions (1.01, IQR 0.59 to 1.48) than those without lesions (0.18, IQR 0.06 to 0.47). The area under the receiver operating characteristic (ROC) curve (AUC) for GFAP in detecting children and youth with traumatic intracranial lesions on CT was 0.82 (95% CI = 0.71 to 0.93). In those presenting with GCS scores of 15, the AUC for detecting lesions was 0.80 (95% CI = 0.68 to 0.92). Similarly, in children under five years old the AUC was 0.83 (95% CI = 0.56 to 1.00). Performance for detecting intracranial lesions at a GFAP cutoff level of 0.15 ng/ml yielded a sensitivity of 94%, a specificity of 47%, and a negative predictive value of 98%. Conclusions In children and youth of all ages, GFAP measured within 6 hours of injury was associated with traumatic intracranial lesions on CT and with severity of TBI. Further study is required to validate these findings before clinical application. PMID:26469937

Gestational changes in left ventricular myocardial contractile function: new insights from two-dimensional speckle tracking echocardiography.

PubMed

Sengupta, Shantanu P; Bansal, Manish; Hofstra, Leonard; Sengupta, Partho P; Narula, Jagat

2017-01-01

The goal of this study was to evaluate the impact of pregnancy and labor on left ventricular (LV) myocardial mechanics using speckle tracking echocardiography (STE). Pregnancy is characterized by profound hormonal and hemodynamic alterations that directly or indirectly influence cardiac structure and function. However, the impact of these changes on left ventricular (LV) myocardial contractile function has not been fully elucidated. In this prospective, longitudinal study, 35 pregnant women underwent serial clinical and echocardiographic evaluation during each trimester and at labor. Two dimensional STE was performed to measure global LV longitudinal, circumferential and radial strain (GLS, GCS and GRS, respectively). Similar data obtained from 20 nulliparous, age-matched women were used as control. All strain values during pregnancy were adjusted for age and hemodynamic parameters. There was a progressive increase in heart rate, systolic and diastolic blood pressure, cardiac output and LV stroke-work during pregnancy. LV end-diastolic and end-systolic volumes also increased progressively but LV ejection fraction remained unaltered, except for slight reduction during the second trimester. Compared to the controls, GLS and GCS were reduced in the first trimester itself (GLS -22.39 ± 5.43 % vs. -18.66 ± 0.64 %, P 0.0002; GCS -20.84 ± 3.20 vs. -17.88 ± 0.09, P < 0.001) and remained so throughout the pregnancy and labor. In contrast, GRS showed an increase during pregnancy which peaked during the second trimester (24.18 ± 0.39 % vs. 18.06 ± 8.14 % in controls, P < 0.001). Alterations in loading conditions during pregnancy are associated with counterbalancing changes in the myocardial mechanics. LV longitudinal and circumferential strain are reduced whereas radial strain is increased. These counterbalancing changes serve to maintain overall LV ejection performance within a normal range and enable the maternal heart to meet the hemodynamic demands of pregnancy and labor.

Effect of inhaled and systemic glucocorticoid treatment on CD4+ regulatory and effector T cells in a mouse model of allergic asthma.

PubMed

Zuśka-Prot, Monika; Maślanka, Tomasz

2017-04-01

To achieve a better understanding of mechanisms underlying the anti-asthmatic action of inhaled and systemic glucocorticoids (GCs) and to provide more data regarding the risk of a negative effect of inhaled GCs on CD4 + T cells, a study was conducted on the effect of ciclesonide and methylprednisolone on CD4 + effector (Teff), regulatory (Treg) and resting (Trest) T cells within respiratory and extra-respiratory tissues in a mouse model of allergic asthma. The study indicated that one, and possibly a key mechanism, underlying the anti-asthmatic action of inhaled and systemic GCs is the prevention of the activation and clonal expansion of CD4 + Teff cells in the mediastinal lymph nodes (MLNs), which consequently prevents infiltration of the lungs with CD4 + Teff cells. The beneficial effects of GCs in asthma treatment were not mediated through increased recruitment of Treg cells into the MLNs and lungs and/or local generation of Treg cells. The results demonstrated that inhaled and systemic GCs induced comparable depletion of normal CD4 + Teff, Trest and Treg cells in the MLNs, head and neck lymph nodes and peripheral blood. Furthermore, inhaled, but not systemic GC therapy, led to the loss of these cells in the lungs. Thus, the study suggests that inhaled GC therapy may not be safer at all than systemic one with respect to the adverse effect on CD4 + T cells present within and outside the respiratory tract. Moreover, administration of inhaled GCs can produce negative effects on lung-residing CD4 + T cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Active Management of Integrated Geothermal-CO2 Storage Reservoirs in Sedimentary Formations

DOE Data Explorer

Buscheck, Thomas A.

2012-01-01

Active Management of Integrated Geothermal–CO2 Storage Reservoirs in Sedimentary Formations: An Approach to Improve Energy Recovery and Mitigate Risk: FY1 Final Report The purpose of phase 1 is to determine the feasibility of integrating geologic CO2 storage (GCS) with geothermal energy production. Phase 1 includes reservoir analyses to determine injector/producer well schemes that balance the generation of economically useful flow rates at the producers with the need to manage reservoir overpressure to reduce the risks associated with overpressure, such as induced seismicity and CO2 leakage to overlying aquifers. Based on a range of well schemes, techno-economic analyses of the levelized cost of electricity (LCOE) are conducted to determine the economic benefits of integrating GCS with geothermal energy production. In addition to considering CO2 injection, reservoir analyses are conducted for nitrogen (N2) injection to investigate the potential benefits of incorporating N2 injection with integrated geothermal-GCS, as well as the use of N2 injection as a potential pressure-support and working-fluid option. Phase 1 includes preliminary environmental risk assessments of integrated geothermal-GCS, with the focus on managing reservoir overpressure. Phase 1 also includes an economic survey of pipeline costs, which will be applied in Phase 2 to the analysis of CO2 conveyance costs for techno-economics analyses of integrated geothermal-GCS reservoir sites. Phase 1 also includes a geospatial GIS survey of potential integrated geothermal-GCS reservoir sites, which will be used in Phase 2 to conduct sweet-spot analyses that determine where promising geothermal resources are co-located in sedimentary settings conducive to safe CO2 storage, as well as being in adequate proximity to large stationary CO2 sources.

A rational use of glucocorticoids in patients with early arthritis has a minimal impact on bone mass

PubMed Central

2010-01-01

Introduction Glucocorticoid (GC)-induced osteoporosis is a frequent complication in patients with rheumatoid arthritis. However, little information exists about the consequences of GC use in patients with early arthritis. Here we describe the variables underlying the use of GC in early arthritis, as well as its effect on bone-mineral density. Methods Data from 116 patients in our early arthritis register were analyzed (90 women; median age, 52.5 years, interquartile range (IQR, 38.5-66); 6-month median disease duration at entry (IQR, 4-9)). In this register, the clinical and treatment information was recorded systematically, including the cumulative GC dose. Lumbar spine, hip, and forearm bone-mineral density (BMD) measurements were performed at entry and after a 2-year follow-up. A multivariate analysis was performed to establish the variables associated with the use of GCs, as well as those associated with variations in BMD. Results Of the patients with early arthritis studied, 67% received GCs during the 2-year follow-up. GCs were more frequently prescribed to elderly patients, those with higher basal disease activity and disability, and patients with positive rheumatoid factor. When adjusted for these variables, GCs were less frequently prescribed to female patients. The use of GCs was associated with an increase of BMD in the ultradistal region of the forearm, although it induced a significant loss of BMD in the medial region of the forearm. No relevant effect of GC was noted on the BMD measured at other locations. Conclusions The frequent use of GCs as a "bridge therapy" in patients with early arthritis does not seem to be associated with relevant loss of bone mass. Moreover, cumulative GC administration might be associated with an increase of juxtaarticular BMD. PMID:20331862

Study of conjunctival flora in anophthalmic patients: influence on the comfort of the socket.

PubMed

Toribio, Alvaro; Marrodán, Teresa; Fernández-Natal, Isabel; Martínez-Blanco, Honorina; Rodríguez-Aparicio, Leandro; Ferrero, Miguel Á

2017-08-01

To investigate the relationship between conjunctival flora and comfort of the socket in anophthalmic patients. A cross-sectional clinical study including 60 patients with unilateral anophthalmia who wear a prosthetic eye. From each patient three microbiological samples were taken from the lower conjunctival sac (healthy eye, pre-prosthesis, and retro-prosthesis space of socket). The 180 samples obtained were cultured. Samples from a randomized subgroup of 29 patients were measured by spectrophotometry at 540 nm after 48 h of growth, to determine their microbial density (MD). The grade of comfort of the socket (GCS) of each patient was established by a questionnaire. Epidemiological and clinical data of the anophthalmic socket and artificial eye care of each patient were also collected. MD decreased in healthy eyes (0.213 ± 0.201, P = 0.004) compared with the pre-prosthesis (0.402 ± 0.323) and retro-prosthesis (0.438 ± 0.268) samples. Pre-prosthesis MD correlated with retro-prosthesis MD (R = 0.401, P = 0.031) and healthy eye MD (R = 0.482, P = 0.008), and it was also related to poor GCS (P = 0.017). Aerobic Gram-negative bacteria in retro-prosthesis samples of patients with poor GCS was higher than in patients with good or fair GCS (P = 0.008). In the same samples, coagulase-negative staphylococci proportion (excluding S. epidermidis) increased in patients with good GCS (P = 0.030). Socket microflora is related to GCS. Increased pathogenic flora, especially Gram-negative bacteria, and high MD are related to discomfort, while coagulase-negative staphylococci (other than S. epidermidis) are associated with comfort.

Natural oil slicks fuel surface water microbial activities in the northern Gulf of Mexico

PubMed Central

Ziervogel, Kai; D'souza, Nigel; Sweet, Julia; Yan, Beizhan; Passow, Uta

2014-01-01

We conducted a series of roller tank incubations with surface seawater from the Green Canyon oil reservoir, northern Gulf of Mexico, amended with either a natural oil slick (GCS-oil) or pristine oil. The goal was to test whether bacterial activities of natural surface water communities facilitate the formation of oil-rich marine snow (oil snow). Although oil snow did not form during any of our experiments, we found specific bacterial metabolic responses to the addition of GCS-oil that profoundly affected carbon cycling within our 4-days incubations. Peptidase and β-glucosidase activities indicative of bacterial enzymatic hydrolysis of peptides and carbohydrates, respectively, were suppressed upon the addition of GCS-oil relative to the non-oil treatment, suggesting that ascending oil and gas initially inhibits bacterial metabolism in surface water. Biodegradation of physically dispersed GCS-oil components, indicated by the degradation of lower molecular weight n-alkanes as well as the rapid transformation of particulate oil-carbon (C: N >40) into the DOC pool, led to the production of carbohydrate- and peptide-rich degradation byproducts and bacterial metabolites such as transparent exopolymer particles (TEP). TEP formation was highest at day 4 in the presence of GCS-oil; in contrast, TEP levels in the non-oil treatment already peaked at day 2. Cell-specific enzymatic activities closely followed TEP concentrations in the presence and absence of GCS-oil. These results demonstrate that the formation of oil slicks and activities of oil-degrading bacteria result in a temporal offset of microbial cycling of organic matter, affecting food web interactions and carbon cycling in surface waters over cold seeps. PMID:24847314

Postoperative surveillance in neurosurgical patients - usefulness of neurological assessment scores and bispectral index.

PubMed

Herrero, Silvia; Carrero, Enrique; Valero, Ricard; Rios, Jose; Fábregas, Neus

We examined the additive effect of the Ramsay scale, Canadian Neurological Scale (CNS), Nursing Delirium Screening Scale (Nu-DESC), and Bispectral Index (BIS) to see whether along with the assessment of pupils and Glasgow Coma Scale (GCS) it improved early detection of postoperative neurological complications. We designed a prospective observational study of two elective neurosurgery groups of patients: craniotomies (CG) and non-craniotomies (NCG). We analyze the concordance and the odds ratio (OR) of altered neurological scales and BIS in the Post-Anesthesia Care Unit (PACU) for postoperative neurological complications. We compared the isolated assessment of pupils and GCS (pupils-GCS) with all the neurologic assessment scales and BIS (scales-BIS). In the CG (n=70), 16 patients (22.9%) had neurological complications in PACU. The scales-BIS registered more alterations than the pupils-GCS (31.4% vs. 20%; p<0.001), were more sensitive (94% vs. 50%) and allowed a more precise estimate for neurological complications in PACU (p=0.002; OR=7.15, 95% CI=2.1-24.7 vs. p=0.002; OR=9.5, 95% CI=2.3-39.4). In the NCG (n=46), there were no neurological complications in PACU. The scales-BIS showed alterations in 18 cases (39.1%) versus 1 (2.2%) with the pupils-GCS (p<0.001). Altered CNS on PACU admission increased the risk of neurological complications in the ward (p=0.048; OR=7.28, 95% CI=1.021-52.006). Applied together, the assessment of pupils, GCS, Ramsay scale, CNS, Nu-DESC and BIS improved early detection of postoperative neurological complications in PACU after elective craniotomies. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[Postoperative surveillance in neurosurgical patients - usefulness of neurological assessment scores and bispectral index].

PubMed

Herrero, Silvia; Carrero, Enrique; Valero, Ricard; Rios, Jose; Fábregas, Neus

We examined the additive effect of the Ramsay scale, Canadian Neurological Scale (CNS), Nursing Delirium Screening Scale (Nu-DESC), and Bispectral Index (BIS) to see whether along with the assessment of pupils and Glasgow Coma Scale (GCS) it improved early detection of postoperative neurological complications. We designed a prospective observational study of two elective neurosurgery groups of patients: craniotomies (CG) and non-craniotomies (NCG). We analyze the concordance and the odds ratio (OR) of altered neurological scales and BIS in the Post-Anesthesia Care Unit (PACU) for postoperative neurological complications. We compared the isolated assessment of pupils and GCS (pupils-GCS) with all the neurologic assessment scales and BIS (scales-BIS). In the CG (n=70), 16 patients (22.9%) had neurological complications in PACU. The scales-BIS registered more alterations than the pupils-GCS (31.4% vs. 20%; p<0.001), were more sensitive (94% vs. 50%) and allowed a more precise estimate for neurological complications in PACU (p=0.002; OR=7.15, 95% CI=2.1-24.7 vs. p=0.002; OR=9.5, 95% CI=2.3-39.4). In the NCG (n=46), there were no neurological complications in PACU. The scales-BIS showed alterations in 18 cases (39.1%) versus 1 (2.2%) with the pupils-GCS (p<0.001). Altered CNS on PACU admission increased the risk of neurological complications in the ward (p=0.048; OR=7.28, 95% CI=1.021-52.006). Applied together, the assessment of pupils, GCS, Ramsay scale, CNS, Nu-DESC and BIS improved early detection of postoperative neurological complications in PACU after elective craniotomies. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Hepatitis B virus-related mortality in rheumatoid arthritis patients undergoing long-term low-dose glucocorticoid treatment: A population-based study.

PubMed

Yang, Sheng-Shun; Hung, Chin-Tun; Li, Shu-Fen; Lee, Horng-Mo; Chung, Yueh-Chin; Chen, Hsin-Hua; Chang, Shu-Chuan

2017-09-04

Glucocorticoids (GC) are commonly used in rheumatoid arthritis (RA) patients which bears a risk of hepatitis B virus (HBV) reactivation. The purpose of this study was to investigate the risk of HBV-related mortality under long-term low-dose GCs in Taiwanese RA patients. We retrospectively analyzed 45,423 RA patients using National Health Insurance Research Database from January 1999 to December 2011. Of them, 2204 patients had the diagnosis of HBV and were classified into four groups according to GCs regimens. Outcome comparison by Cox model analysis for liver-related mortality was performed. In this cohort, 90.5% were older than 40. One hundred and five patients had been treated with short-term large-dose GCs (Group A); 862 patients received GCs ≥20 mg/day for ≥3 days or a variable dose but did not meet Group C criteria (Group B); 689 patients were continuously treated with low-dose (<20 mg/day) GCs for ≥3 months for at least one session (Group C); and 548 patients had never been exposed to GCs (Group D). Two hundred and sixty-one patients had been exposed to antiviral agents, which was significantly higher in Group C. Fifty-eight patients (2.63%) died of acute hepatic failure, while no statistically significant difference between each groups (p = 0.074). Groups C and D comparison by two-sample test showed that long-term low-dose GC treatment was not associated with liver-related death after adjusting for malignancy. Long-term low-dose GC treatment was not associated with liver-related mortality in RA with concomitant HBV patients probably due to commonly applied antiviral therapy by rheumatologists. Copyright © 2017. Published by Elsevier B.V.

Pityriasis Rosea, Gianotti-Crosti Syndrome, Asymmetric Periflexural Exanthem, Papular-Purpuric Gloves and Socks Syndrome, Eruptive Pseudoangiomatosis, and Eruptive Hypomelanosis: Do Their Epidemiological Data Substantiate Infectious Etiologies?

PubMed Central

Zawar, Vijay; Sciallis, Gabriel F.; Kempf, Werner; Lee, Albert

2016-01-01

Many clinical and laboratory-based studies have been reported for skin rashes which may be due to viral infections, namely pityriasis rosea (PR), Gianotti-Crosti syndrome (GCS), asymmetric periflexural exanthem/unilateral laterothoracic exanthem (APE/ULE), papular-purpuric gloves and socks syndrome (PPGSS), and eruptive pseudo-angiomatosis (EP). Eruptive hypomelanosis (EH) is a newly discovered paraviral rash. Novel tools are now available to investigate the epidemiology of these rashes. To retrieve epidemiological data of these exanthema and analyze whether such substantiates or refutes infectious etiologies. We searched for articles published over the last 60 years and indexed by PubMed database. We then analyzed them for universality, demography, concurrent patients, temporal and spatial-temporal clustering, mini-epidemics, epidemics, and other clinical and geographical associations. Based on our criteria, we selected 55, 60, 29, 36, 20, and 4 articles for PR, GCS, APE/ULE, PPGSS, EP, and EH respectively. Universality or multiple-continental reports are found for all exanthema except EH. The ages of patients are compatible with infectious causes for PR, GCS, APE/ULE, and EH. Concurrent patients are reported for all. Significant patient clustering is demonstrated for PR and GCS. Mini-epidemics and epidemics have been reported for GCS, EP, and EH. The current epidemiological data supports, to a moderate extent, that PR, GCS, and APE could be caused by infectious agents. Support for PPGSS is marginal. Epidemiological evidences for infectious origins for EP and EH are inadequate. There might be growing epidemiological evidence to substantiate or to refute our findings in the future. PMID:27103975

Limits on runaway growth of intermediate mass black holes from advanced LIGO

NASA Astrophysics Data System (ADS)

Kovetz, Ely D.; Cholis, Ilias; Kamionkowski, Marc; Silk, Joseph

2018-06-01

There is growing evidence that intermediate-mass black holes (IMBHs), defined here as having a mass in the range M =500 -105 M⊙ , are present in the dense centers of certain globular clusters (GCs). Gravitational waves from their mergers with other IMBHs or with stellar BHs in the cluster are mostly emitted in frequencies ≲10 Hz , which unfortunately is out of reach for current ground-based observatories such as advanced LIGO (aLIGO). Nevertheless, we show that aLIGO measurements can be used to efficiently probe one of the possible formation mechanisms of IMBHs in GCs, namely a runaway merger process of stellar seed BHs. In this case, aLIGO will be sensitive to the lower-mass rungs of the merger ladder, ranging from the seed BH mass to masses ≳50 - 300 M⊙ , where the background from standard mergers is expected to be very low. Assuming this generic IMBH formation scenario, we calculate the mass functions that correspond to the limiting cases of possible merger trees. Based on estimates for the number density of GCs and taking into account the instrumental sensitivity, we show that current observations do not effectively limit the occupation fraction focc of IMBHs formed by runaway mergers of stellar BHs in GCs. However, we find that if runaway mergers occur steadily throughout the lifetimes of GCs (as opposed to happening mainly early in their lifetimes), then a six-year run of aLIGO at design sensitivity will be able to probe down to focc≲3 % at a 99.9% confidence level, either finding evidence for this formation mechanism, or necessitating others if the fraction of GCs that harbor IMBHs is higher.

Milky Way globular cluster metallicity and low-mass X-ray binaries: the red giant influence

NASA Astrophysics Data System (ADS)

Vulic, N.; Barmby, P.; Gallagher, S. C.

2018-02-01

Galactic and extragalactic studies have shown that metal-rich globular clusters (GCs) are approximately three times more likely to host bright low-mass X-ray binaries (LMXBs) than metal-poor GCs. There is no satisfactory explanation for this metallicity effect. We tested the hypothesis that the number density of red giant branch (RGB) stars is larger in metal-rich GCs, and thus potentially the cause of the metallicity effect. Using Hubble Space Telescope photometry for 109 unique Milky Way GCs, we investigated whether RGB star density was correlated with GC metallicity. Isochrone fitting was used to calculate the number of RGB stars, which were normalized by the GC mass and fraction of observed GC luminosity, and determined density using the volume at the half-light radius (rh). The RGB star number density was weakly correlated with metallicity [Fe/H], giving Spearman and Kendall Rank test p-values of 0.000 16 and 0.000 21 and coefficients rs = 0.35 and τ = 0.24, respectively. This correlation may be biased by a possible dependence of rh on [Fe/H], although studies have shown that rh is correlated with Galactocentric distance and independent of [Fe/H]. The dynamical origin of the rh-metallicity correlation (tidal stripping) suggests that metal-rich GCs may have had more active dynamical histories, which would promote LMXB formation. No correlation between the RGB star number density and metallicity was found when using only the GCs that hosted quiescent LMXBs. A complete census of quiescent LMXBs in our Galaxy is needed to further probe the metallicity effect, which will be possible with the upcoming launch of eROSITA.

NGC 6535: the lowest mass Milky Way globular cluster with a Na-O anti-correlation? Cluster mass and age in the multiple population context

NASA Astrophysics Data System (ADS)

Bragaglia, A.; Carretta, E.; D'Orazi, V.; Sollima, A.; Donati, P.; Gratton, R. G.; Lucatello, S.

2017-11-01

To understand globular clusters (GCs) we need to comprehend how their formation process was able to produce their abundance distribution of light elements. In particular, we seek to figure out which stars imprinted the peculiar chemical signature of GCs. One of the best ways is to study the light-element anti-correlations in a large sample of GCs that are analysed homogeneously. As part of our spectroscopic survey of GCs with FLAMES, we present here the results of our study of about 30 red giant member stars in the low-mass, low-metallicity Milky Way cluster NGC 6535. We measured the metallicity (finding [Fe/H] =-1.95, rms = 0.04 dex in our homogeneous scale) and other elements of the cluster and, in particular, we concentrate here on O and Na abundances. These elements define the normal Na-O anti-correlation of classical GCs, making NGC 6535 perhaps the lowest mass cluster with a confirmed presence of multiple populations. We updated the census of Galactic and extragalactic GCs for which a statement on the presence or absence of multiple populations can be made on the basis of high-resolution spectroscopy preferentially, or photometry and low-resolution spectroscopy otherwise; we also discuss the importance of mass and age of the clusters as factors for multiple populations. Based on observations collected at ESO telescopes under programme 093.B-0583.Table 2 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/607/A44

Activation of the sigma receptor 1 modulates AMPA receptor-mediated light-evoked excitatory postsynaptic currents in rat retinal ganglion cells.

PubMed

Liu, Lei-Lei; Deng, Qin-Qin; Weng, Shi-Jun; Yang, Xiong-Li; Zhong, Yong-Mei

2016-09-22

Sigma receptor (σR), a unique receptor family, is classified into three subtypes: σR1, σR2 and σR3. It was previously shown that σR1 activation induced by 1μM SKF10047 (SKF) suppressed N-methyl-d-aspartate (NMDA) receptor-mediated responses of rat retinal ganglion cells (GCs) and the suppression was mediated by a distinct Ca(2+)-dependent phospholipase C (PLC)-protein kinase C (PKC) pathway. In the present work, using whole-cell patch-clamp techniques in rat retinal slice preparations, we further demonstrate that SKF of higher dosage (50μM) significantly suppressed AMPA receptor (AMPAR)-mediated light-evoked excitatory postsynaptic currents (L-EPSCs) of retinal ON-type GCs (ON GCs), and the effect was reversed by the σR1 antagonist BD1047, suggesting the involvement of σR1. The SKF (50μM) effect was unlikely due to a change in glutamate release from bipolar cells, as suggested by the unaltered paired-pulse ratio (PPR) of AMPAR-mediated EPSCs of ON GCs. SKF (50μM) did not change L-EPSCs of ON GCs when the G protein inhibitor GDP-β-S or the protein kinase G (PKG) inhibitor KT5823 was intracellularly infused. Calcium imaging further revealed that SKF (50μM) did not change intracellular calcium concentration in GCs and persisted to suppress L-EPSCs when intracellular calcium was chelated by BAPTA. The SKF (50μM) effect was intact when protein kinase A (PKA) and phosphatidylinostiol (PI)-PLC signaling pathways were both blocked. We conclude that the SKF (50μM) effect is Ca(2+)-independent, PKG-dependent, but not involving PKA, PI-PLC pathways. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Actions of glucocorticoids at a seasonal baseline as compared to stress-related levels in the regulation of periodic life processes.

PubMed

Landys, Meta M; Ramenofsky, Marilyn; Wingfield, John C

2006-09-01

For decades, demands associated with the predictable life-history cycle have been considered stressful and have not been distinguished from stress that occurs in association with unpredictable and life-threatening perturbations in the environment. The recent emergence of the concept of allostasis distinguishes behavioral and physiological responses to predictable routines as opposed to unpredictable perturbations, and allows for their comparison within one theoretical framework. Glucocorticosteroids (GCs) have been proposed as important mediators of allostasis, as they allow for rapid readjustment and support of behavior and physiology in response to predictable and unpredictable demands (allostatic load). Much work has already been done in defining GC action at the high concentrations that accompany life-threatening perturbations. However, less is known about the role of GCs in relation to daily and seasonal life processes. In this review, we summarize the known behavioral and physiological effects of GCs relating to the predictable life-history cycle, paying particular attention to feeding behavior, locomotor activity and energy metabolism. Although we utilize a comparative approach, emphasis is placed on birds. In addition, we briefly review effects of GCs at stress-related concentrations to test the hypothesis that different levels of GCs play specific and distinct roles in the regulation of life processes and, thus, participate in the promotion of different physiological states. We also examine the receptor types through which GC action may be mediated and suggest mechanisms whereby different GC concentrations may exert their actions. In conclusion, we argue that biological actions of GCs at "non-stress" seasonal concentrations play a critical role in the adjustment of responses that accompany predictable variability in the environment and demand more careful consideration in future studies.

Necrotizing soft tissue infections caused by Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis of groups C and G in western Norway.

PubMed

Bruun, T; Kittang, B R; de Hoog, B J; Aardal, S; Flaatten, H K; Langeland, N; Mylvaganam, H; Vindenes, H A; Skrede, S

2013-12-01

Streptococcus pyogenes (group A streptococcus, GAS) is a major cause of necrotizing soft tissue infection (NSTI). On rare occasions, other β-haemolytic streptococci may also cause NSTI, but the significance and nature of these infections has not been thoroughly investigated. In this study, clinical and molecular characteristics of NSTI caused by GAS and β-haemolytic Streptococcus dysgalactiae subsp. equisimilis of groups C and G (GCS/GGS) in western Norway during 2000-09 are presented. Clinical data were included retrospectively. The bacterial isolates were subsequently emm typed and screened for the presence of genes encoding streptococcal superantigens. Seventy cases were identified, corresponding to a mean annual incidence rate of 1.4 per 100 000. Sixty-one of the cases were associated with GAS, whereas GCS/GGS accounted for the remaining nine cases. The in-hospital case fatality rates of GAS and GCS/GGS disease were 11% and 33%, respectively. The GCS/GGS patients were older, had comorbidities more often and had anatomically more superficial disease than the GAS patients. High age and toxic shock syndrome were associated with mortality. The Laboratory Risk Indicator for Necrotizing Fasciitis laboratory score showed high values (≥6) in only 31 of 67 cases. Among the available 42 GAS isolates, the most predominant emm types were emm1, emm3 and emm4. The virulence gene profiles were strongly correlated to emm type. The number of superantigen genes was low in the four available GCS/GGS isolates. Our findings indicate a high frequency of streptococcal necrotizing fasciitis in our community. GCS/GGS infections contribute to the disease burden, but differ from GAS cases in frequency and predisposing factors. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

Natural oil slicks fuel surface water microbial activities in the northern Gulf of Mexico.

PubMed

Ziervogel, Kai; D'Souza, Nigel; Sweet, Julia; Yan, Beizhan; Passow, Uta

2014-01-01

We conducted a series of roller tank incubations with surface seawater from the Green Canyon oil reservoir, northern Gulf of Mexico, amended with either a natural oil slick (GCS-oil) or pristine oil. The goal was to test whether bacterial activities of natural surface water communities facilitate the formation of oil-rich marine snow (oil snow). Although oil snow did not form during any of our experiments, we found specific bacterial metabolic responses to the addition of GCS-oil that profoundly affected carbon cycling within our 4-days incubations. Peptidase and β-glucosidase activities indicative of bacterial enzymatic hydrolysis of peptides and carbohydrates, respectively, were suppressed upon the addition of GCS-oil relative to the non-oil treatment, suggesting that ascending oil and gas initially inhibits bacterial metabolism in surface water. Biodegradation of physically dispersed GCS-oil components, indicated by the degradation of lower molecular weight n-alkanes as well as the rapid transformation of particulate oil-carbon (C: N >40) into the DOC pool, led to the production of carbohydrate- and peptide-rich degradation byproducts and bacterial metabolites such as transparent exopolymer particles (TEP). TEP formation was highest at day 4 in the presence of GCS-oil; in contrast, TEP levels in the non-oil treatment already peaked at day 2. Cell-specific enzymatic activities closely followed TEP concentrations in the presence and absence of GCS-oil. These results demonstrate that the formation of oil slicks and activities of oil-degrading bacteria result in a temporal offset of microbial cycling of organic matter, affecting food web interactions and carbon cycling in surface waters over cold seeps.

The influence of various therapeutic regimens on early clinical and laboratory response and outcome of children with secondary hemophagocytic lymphohistiocytosis

PubMed Central

Gietka, Piotr; Książyk, Janusz B.; Machaczka, Maciej

2016-01-01

Introduction Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening syndrome of severe hyperinflammation which is often triggered by infection or autoimmune disease (macrophage activation syndrome – MAS). The aim of our study was to assess the frequency of sHLH/MAS in children treated in our institution and to compare the effectiveness of various therapeutic interventions. Material and methods Between 2005 and 2013, 24 children (age: 1–17 years) were consecutively treated for sHLH/MAS. Therapy was based on glucocorticoids (GCs) in high or standard doses (hd-GCs or sd-GCs), intravenous immunoglobulin (IVIG), and cyclosporin A (CyA). A comparison of selected laboratory and clinical parameters during the first 72 h of treatment and after a week from the last intervention applied in the first 72 h after diagnosis was performed retrospectively. Results The majority of patients (14/24, 58%) suffered from sHLH/MAS in the course of an autoimmune disease (12 patients diagnosed with a systemic form of juvenile idiopathic arthritis). We found with a confidence level of 95% that the application of hd-GCs in the first 24 h caused rapid alleviation of fever, reduction of hepatosplenomegaly, and an increase in thrombocytes and s-fibrinogen concentrations. The use of combination therapy with hd-GCs, IVIG, and CyA in the first 72 h caused a faster increase in s-fibrinogen. All patients survived and were alive at the follow-up of 1–8 years. Conclusions The results indicate that treatment of sHLH/MAS based on hd-GCs, CyA and IVIG is an effective therapy in children. PMID:29379544

[Risk factors for surgical site infections in patients undergoing craniotomy].

PubMed

Cha, Kyeong-Sook; Cho, Ok-Hee; Yoo, So-Yeon

2010-04-01

The objectives of this study were to determine the prevalence, incidence, and risk factors for postoperative surgical site infections (SSIs) after craniotomy. This study was a retrospective case-control study of 103 patients who had craniotomies between March 2007 and December 2008. A retrospective review of prospectively collected databases of consecutive patients who underwent craniotomy was done. SSIs were defined by using the Centers for Disease Control criteria. Twenty-six cases (infection) and 77 controls (no infection) were matched for age, gender and time of surgery. Descriptive analysis, t-test, X(2)-test and logistic regression analyses were used for data analysis. The statistical difference between cases and controls was significant for hospital length of stay (>14 days), intensive care unit stay more than 15 days, Glasgrow Coma Scale (GCS) score (< or = 7 days), extra-ventricular drainage and coexistent infection. Risk factors were identified by logistic regression and included hospital length of stay of more than 14 days (odds ratio [OR]=23.39, 95% confidence interval [CI]=2.53-216.11) and GCS score (< or = 7 scores) (OR=4.71, 95% CI=1.64-13.50). The results of this study show that patients are at high risk for infection when they have a low level of consciousness or their length hospital stay is long term. Nurses have to take an active and continuous approach to infection control to help with patients having these risk factors.

Recent improvements of reactor physics codes in MHI

NASA Astrophysics Data System (ADS)

Kosaka, Shinya; Yamaji, Kazuya; Kirimura, Kazuki; Kamiyama, Yohei; Matsumoto, Hideki

2015-12-01

This paper introduces recent improvements for reactor physics codes in Mitsubishi Heavy Industries, Ltd(MHI). MHI has developed a new neutronics design code system Galaxy/Cosmo-S(GCS) for PWR core analysis. After TEPCO's Fukushima Daiichi accident, it is required to consider design extended condition which has not been covered explicitly by the former safety licensing analyses. Under these circumstances, MHI made some improvements for GCS code system. A new resonance calculation model of lattice physics code and homogeneous cross section representative model for core simulator have been developed to apply more wide range core conditions corresponding to severe accident status such like anticipated transient without scram (ATWS) analysis and criticality evaluation of dried-up spent fuel pit. As a result of these improvements, GCS code system has very wide calculation applicability with good accuracy for any core conditions as far as fuel is not damaged. In this paper, the outline of GCS code system is described briefly and recent relevant development activities are presented.

A case report on near manual strangulation and glasgow coma scale.

PubMed

Meel Banwari, L

2015-09-01

Glasgow Coma Scale (GCS) is considered as a gold standard in estimating the prognosis of the comatose patient. The management of the patient relies heavily on this scale. The mechanism of injury must also be included in scoring of the GCS. Survival from strangulation is uncommon, and if it occurs, it is often associated with various complications such as neurological consequences. To highlight a poor correlation with low GCS and ultimate outcome in cases of manual strangulation. This is a case report of young female adult who was raped and manually strangulated by a colleague during a training course for traditional healers. She was admitted with very low (3/15) Glasgow Coma Scale (GCS) and presumed to have a poor prognosis. She was rigorously ventilated in Intensive Care Unit (ICU), and was discharged from hospital after a week without any complications. The neck and genital injuries are described. This report discusses. A low Glasgow Coma Scale is not a predictive of poor prognosis in cases of manual strangulation.

Mapping out the origins of compact stellar systems

NASA Astrophysics Data System (ADS)

Romanowsky, Aaron J.; Brodie, Jean P.; SAGES Collaboration

2017-03-01

We present a suite of extragalactic explorations of the origins and nature of globular clusters (GCs) and ultra-compact dwarfs (UCDs), and the connections between them. An example of GC metallicity bimodality is shown to reflect underlying, distinct metal-poor and metal-rich stellar halo populations. Metallicity-matching methods are used to trace the birth sites and epochs of GCs in giant E/S0s, pointing to clumpy disk galaxies at z ~ 3 for the metal-rich GCs, and to a combination of accreted and in-situ formation modes at z ~ 5-6 for the metal-poor GCs. An increasingly diverse zoo of compact stellar systems is being discovered, including objects that bridge the gaps between UCDs and faint fuzzies, and between UCDs and compact ellipticals. Many of these have properties pointing to origins as the stripped nuclei of larger galaxies, and a smoking-gun example is presented of an ω Cen-like star cluster embedded in a tidal stream.

Recent improvements of reactor physics codes in MHI

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

Kosaka, Shinya, E-mail: shinya-kosaka@mhi.co.jp; Yamaji, Kazuya; Kirimura, Kazuki

2015-12-31

This paper introduces recent improvements for reactor physics codes in Mitsubishi Heavy Industries, Ltd(MHI). MHI has developed a new neutronics design code system Galaxy/Cosmo-S(GCS) for PWR core analysis. After TEPCO’s Fukushima Daiichi accident, it is required to consider design extended condition which has not been covered explicitly by the former safety licensing analyses. Under these circumstances, MHI made some improvements for GCS code system. A new resonance calculation model of lattice physics code and homogeneous cross section representative model for core simulator have been developed to apply more wide range core conditions corresponding to severe accident status such like anticipatedmore » transient without scram (ATWS) analysis and criticality evaluation of dried-up spent fuel pit. As a result of these improvements, GCS code system has very wide calculation applicability with good accuracy for any core conditions as far as fuel is not damaged. In this paper, the outline of GCS code system is described briefly and recent relevant development activities are presented.« less

Generalized Chirp Scaling Combined with Baseband Azimuth Scaling Algorithm for Large Bandwidth Sliding Spotlight SAR Imaging

PubMed Central

Yi, Tianzhu; He, Zhihua; He, Feng; Dong, Zhen; Wu, Manqing

2017-01-01

This paper presents an efficient and precise imaging algorithm for the large bandwidth sliding spotlight synthetic aperture radar (SAR). The existing sub-aperture processing method based on the baseband azimuth scaling (BAS) algorithm cannot cope with the high order phase coupling along the range and azimuth dimensions. This coupling problem causes defocusing along the range and azimuth dimensions. This paper proposes a generalized chirp scaling (GCS)-BAS processing algorithm, which is based on the GCS algorithm. It successfully mitigates the deep focus along the range dimension of a sub-aperture of the large bandwidth sliding spotlight SAR, as well as high order phase coupling along the range and azimuth dimensions. Additionally, the azimuth focusing can be achieved by this azimuth scaling method. Simulation results demonstrate the ability of the GCS-BAS algorithm to process the large bandwidth sliding spotlight SAR data. It is proven that great improvements of the focus depth and imaging accuracy are obtained via the GCS-BAS algorithm. PMID:28555057

Surface Compositions of Red Giant Stars in Globular Clusters

NASA Astrophysics Data System (ADS)

Cheng, Eric; Lau, Marie; Smith, Graeme; Chen, Brian

2018-01-01

Globular clusters (GCs) are excellent “laboratories” to study the formation and evolution of our galaxy. In order to understand, more specifically, the chemical compositions and stellar evolution of the stars in GCs, we ask whether or not deep internal mixing occurs in red giants or if in fact the compositions come from the primordial interstellar medium or previous generations of stars. It has been discovered that as a star evolves up the red giant branch, the surface carbon abundance decreases, which is evidence of deep internal mixing. We questioned whether these processes also affect O or Na abundance as a star evolves. We collected measurement data of red giants from GCs out of academic journals and sorted the data into catalogs. Then, we plotted the catalogs into figures, comparing surface O and Na each with stellar luminosity. Statistical tests were ran to quantify the amount of correlation between the variables. Out of 27 GCs, we concluded that eight show a positive correlation between Na and luminosity, and two show a negative correlation between O and luminosity. Properties of GCs were compared to determine if chemical distribution in stars depends on GCs as the self-enrichment scenario suggests. We created histograms of sodium distribution to test for bimodality to examine if there are separate trends in each GC. In six GCs, two different sequences of red giants appear for Na versus luminosity, suggesting evidence that the depth of mixing may differ among each red giant in a GC. This study has provided new evidence that the changing chemical abundances on the surfaces of red giants can be due to stellar evolutionary effects and deep internal mixing, which may not necessarily depend on the GC and may differ in depth among each red giant. Through this study, we learn more about stellar evolution which will eventually help us understand the origins of our universe. Most of this work was carried out by high school students working under the auspices of the Science Internship Program (SIP) at UC Santa Cruz.

The Survey of Centaurus A's Baryonic Structures (SCABS) - II. The extended globular cluster system of NGC 5128 and its nearby environment

NASA Astrophysics Data System (ADS)

Taylor, Matthew A.; Puzia, Thomas H.; Muñoz, Roberto P.; Mieske, Steffen; Lançon, Ariane; Zhang, Hongxin; Eigenthaler, Paul; Bovill, Mia Sauda

2017-08-01

New wide-field u΄g΄r΄I΄z΄ Dark Energy Camera observations centred on the nearby giant elliptical galaxy NGC 5128 covering ˜21 deg2 are used to compile a new catalogue of ˜3200 globular clusters (GCs). We report 2404 newly identified candidates, including the vast majority within ˜140 kpc of NGC 5128. We find evidence for a transition at a galactocentric radius of Rgc ≈ 55 kpc from GCs 'intrinsic' to NGC 5128 to those likely to have been accreted from dwarf galaxies or that may transition to the intragroup medium of the Centaurus A galaxy group. We fit power-law surface number density profiles of the form Σ _{N, R_gc}∝ R_gc^Γ and find that inside the transition radius, the red GCs are more centrally concentrated than the blue, with Γinner, red ≈ -1.78 and Γinner, blue ≈ -1.40, respectively. Outside this region both profiles flatten, more dramatically for the red GCs (Γouter, red ≈ -0.33) compared to the blue (Γouter, blue ≈ -0.61), although the former is more likely to suffer contamination by background sources. The median (g΄ - z΄)0 = 1.27 mag colour of the inner red population is consistent with arising from the amalgamation of two giant galaxies each less luminous than present-day NGC 5128. Both inwards and outwards of the transition radius, we find the fraction of blue GCs to dominate over the red GCs, indicating a lively history of minor mergers. Assuming the blue GCs to originate primarily in dwarf galaxies, we model the population required to explain them, while remaining consistent with NGC 5128's present-day spheroid luminosity. We find that several dozen dwarfs of luminosities Ldw, V ≃ 106-9.3 LV, ⊙, following a Schechter luminosity function with a faint-end slope of -1.50 ≲ α ≲ -1.25 is favoured, many of which may have already been disrupted in NGC 5128's tidal field.

Efficacy and safety of selective glucocorticoid receptor modulators in comparison to glucocorticoids in arthritis, a systematic review.

PubMed

Safy, M; de Hair, M J H; Jacobs, J W G; Buttgereit, F; Kraan, M C; van Laar, J M

2017-01-01

Long-term treatment with glucocorticoids (GCs) plays an important role in the management of arthritis patients, although the efficacy/safety balance is unfavorable. Alternatives with less (severe) adverse effects but with good efficacy are needed. Selective GC receptor modulators (SGRMs) are designed to engage the GC receptor with dissociative characteristics: transactivation of genes, which is mainly responsible for unwanted effects, is less strong while trans-repression of genes, reducing inflammation, is maintained. It is expected that SGRMs thus have a better efficacy/safety balance than GCs. A systematic review providing an overview of the evidence in arthritis is lacking. To systematically review the current literature on efficacy and safety of oral SGRMs in comparison to GCs in arthritis. A search was performed in Medline, Embase and the Cochrane Library, from inception dates of databases until May 2017. Experimental studies involving animal arthritis models or human material of arthritis patients, as well as clinical studies in arthritis patients were included, provided they reported original data. All types of arthritis were included. Data was extracted on the SGRM studied and on the GC used as reference standard; the design or setting of the study was extracted as well as the efficacy and safety results. A total of 207 articles was retrieved of which 17 articles were eligible for our analysis. Two studies concerned randomized controlled trials (RCT), five studies were pre-clinical studies using human material, and 10 studies involved pre-clinical animal models (acute and/or chronic arthritis induced in mice or rats). PF-04171327, the only compound investigated in a clinical trial setting, had a better efficacy/safety balance compared to GCs: better clinical anti-inflammatory efficacy and similar safety. Studies assessing both efficacy and safety of SGRMs are scarce. There is limited evidence for dissociation of anti-inflammatory and metabolic effects of the SGRMs studied. Development of many SGRMs is haltered in a preclinical phase. One SGRM showed a better clinical efficacy/safety balance.

Hypoxia causes IL-8 secretion, Charcot Leyden crystal formation, and suppression of corticosteroid-induced apoptosis in human eosinophils.

PubMed

Porter, L M; Cowburn, A S; Farahi, N; Deighton, J; Farrow, S N; Fiddler, C A; Juss, J K; Condliffe, A M; Chilvers, E R

2017-06-01

Inflamed environments are typically hypercellular, rich in pro-inflammatory cytokines, and profoundly hypoxic. While the effects of hypoxia on neutrophil longevity and function have been widely studied, little is known about the consequences of this stimulus on eosinophils. We sought to investigate the effects of hypoxia on several key aspects of eosinophil biology, namely secretion, survival, and their sensitivity to glucocorticosteroids (GCS), agents that normally induce eosinophil apoptosis. Eosinophils derived from patients with asthma/atopy or healthy controls were incubated under normoxia and hypoxia, with or without glucocorticoids. Activation was measured by flow cytometry, ELISA of cultured supernatants, and F-actin staining; apoptosis and efferocytosis by morphology and flow cytometry; and GCS efficacy by apoptosis assays and qPCR. Hypoxic incubation (3 kPa) caused (i) stabilization of HIF-2α and up-regulation of hypoxia-regulated genes including BNIP3 (BCL2/adenovirus E1B 19-kDa protein-interacting protein 3) and GLUT1 (glucose transporter 1); (ii) secretion of pre-formed IL-8, and Charcot Leyden crystal (CLC) formation, which was most evident in eosinophils derived from atopic and asthmatic donors; (iii) enhanced F-actin formation; (iv) marked prolongation of eosinophil lifespan (via a NF-κB and Class I PI3-kinase-dependent mechanism); and (v) complete abrogation of the normal pro-apoptotic effect of dexamethasone and fluticasone furoate. This latter effect was evident despite preservation of GCS-mediated gene transactivation under hypoxia. These data indicate that hypoxia promotes an eosinophil pro-inflammatory phenotype by enhancing eosinophil secretory function, delaying constitutive apoptosis, and importantly, antagonizing the normal pro-apoptotic effect of GCS. As eosinophils typically accumulate at sites that are relatively hypoxic, particularly during periods of inflammation, these findings may have important implications to understanding the behaviour of these cells in vivo. © 2016 John Wiley & Sons Ltd.

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

PubMed

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

1999-01-01

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

The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury.

PubMed

Shakur, Haleema; Andrews, Peter; Asser, Toomas; Balica, Laura; Boeriu, Cristian; Quintero, Juan Diego Ciro; Dewan, Yashbir; Druwé, Patrick; Fletcher, Olivia; Frost, Chris; Hartzenberg, Bennie; Mantilla, Jorge Mejia; Murillo-Cabezas, Francisco; Pachl, Jan; Ravi, Ramalingam R; Rätsep, Indrek; Sampaio, Cristina; Singh, Manmohan; Svoboda, Petr; Roberts, Ian

2009-12-03

Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor. Adults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE), mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS), the Disability Rating Scale (DRS) and a modified version of the Oxford Handicap Scale (HIREOS). 228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163) in the combined Anatibant treated group, compared to 19.3% (11/57) in the placebo group (relative risk = 1.37; 95% CI 0.76 to 2.46). All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36). The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures. This trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in the risk of serious adverse events was reduced. This trial provides no reliable evidence of benefit or harm and a larger trial would be needed to establish safety and effectiveness. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN23625128.

Probing the outer limits of a galactic halo - deep imaging of exceptionally remote globular clusters in M31

NASA Astrophysics Data System (ADS)

Mackey, Dougal

2011-10-01

Globular clusters {GCs} are fossil relics from which we can obtain critical insights into the formation and growth of galaxies. As part of the ongoing Pan-Andromeda Archaeological Survey {PAndAS} we have discovered a group of exceptionally remote GCs in the M31 halo, spanning a range in projected galactocentric distance of 85-145 kpc. Here we apply for deep ACS imaging of 13 such targets, which will allow us to study their constituent stellar populations, line-of-sight distances, and structural parameters. Our measurements will facilitate the use of these GCs as a unique set of probes of the exceptionally remote halo of a large disk galaxy, opening up a completely new area of parameter space to observational constraint. Comparing the properties of our targets with more centrally-located objects will provide a much clearer picture of the M31 GC population than is presently available, while comparison with the outermost Milky Way GCs will further elucidate well-known disparities between the two systems and offer vital clues to differences in their assembly. In addition, our measurements will substantially augment a broad swathe of science that is presently underway - including probing the dark mass distribution in M31 at very large radii, and investigating the detailed chemical composition of M31 GCs via high-resolution integrated-light spectroscopy.

Interleukin-2-induced survival of natural killer (NK) cells involving phosphatidylinositol-3 kinase-dependent reduction of ceramide through acid sphingomyelinase, sphingomyelin synthase, and glucosylceramide synthase.

PubMed

Taguchi, Yoshimitsu; Kondo, Tadakazu; Watanabe, Mitsumasa; Miyaji, Michihiko; Umehara, Hisanori; Kozutsumi, Yasunori; Okazaki, Toshiro

2004-11-15

Interleukin 2 (IL-2) rescued human natural killer (NK) KHYG-1 cells from apoptosis along with a reduction of ceramide. Conversely, an increase of ceramide inhibited IL-2-rescued survival. IL-2 deprivation-induced activation of acid sphingomyelinase (SMase) and inhibition of glucosylceramide synthase (GCS) and sphingomyelin synthase (SMS) were normalized by IL-2 supplementation. A phosphatidyl inositol-3 (PI-3) kinase inhibitor, LY294002, inhibited IL-2-rescued survival, but a mitogen-activated protein kinase inhibitor, PD98059, and an inhibitor of Janus tyrosine kinase/signal transducer and activator of transcription pathway, AG490, did not. LY294002 inhibited IL-2-induced reduction of ceramide through activation of acid SMase and inhibition of GCS and SMS, suggesting the positive involvement of PI-3 kinase in ceramide reduction through enzymatic regulation. Indeed, a constitutively active PI-3 kinase enhanced growth rate and ceramide reduction through inhibition of acid SMase and activation of GCS and SMS. Further, LY294002 inhibited IL-2-induced changes of transcriptional level as well as mRNA and protein levels in acid SMase and GCS but did not affect the stability of the mRNAs. These results suggest that PI-3 kinase-dependent reduction of ceramide through regulation of acid SMase, GCS, and SMS plays a role in IL-2-rescued survival of NK cells.

Graduated Compression Stockings for Runners: Friend, Foe, or Fake?

PubMed Central

Bovenschen, H. Jorn; te Booij, Mariëlle; van der Vleuten, Carine J. M.

2013-01-01

Objective: To assess the effect of graduated compression stockings (GCS) on lower leg volume and leg complaints in runners during and after exercise. Design: Cross-sectional study. Setting: Radboud University Nijmegen Medical Centre and an outdoor running track in Nijmegen, The Netherlands. Patients or Other Participants: Thirteen Dutch trained recreational runners. Intervention(s): Participants used a GCS on 1 leg during running. Main Outcome Measures: (1) Lower leg volume of both legs was measured at baseline, directly after running, and at 5 minutes and 30 minutes after running using a validated perometer. (2) Leg complaints were reported on questionnaires at set intervals. Results: (1) In both experiments, the legs with GCS showed a reduction in mean (± SEM) leg volume directly after running, as compared with the leg without GCS: −14.1 ± 7.6 mL (P = .04) for the 10-km running track and −53.5 ± 17.8 mL (P = .03) for the maximum exercise test. This effect was not observed at 5 and 30 minutes after running. (2) No differences in leg complaints were reported in either experiment. Conclusions: The GCS prevented an increase in leg volume just after the running exercise. However, this result was not accompanied by a reduction in subjective questionnaire-reported leg complaints. The practical consequences of the present findings need further study. PMID:23672387

Study of Remote Globular Cluster Satellites of M87

NASA Astrophysics Data System (ADS)

Sahai, Arushi; Shao, Andrew; Toloba, Elisa; Guhathakurta, Puragra; Peng, Eric W.; Zhang, Hao

2017-01-01

We present a sample of “orphan” globular clusters (GCs) with previously unknown parent galaxies, which we determine to be remote satellites of M87, a massive elliptical galaxy at the center of the Virgo Cluster of Galaxies. Because GCs were formed in the early universe along with their original parent galaxies, which were cannibalized by massive galaxies such as M87, they share similar age and chemical properties. In this study, we first confirm that M87 is the adoptive parent galaxy of our orphan GCs using photometric and spectroscopic data to analyze spatial and velocity distributions. Next, we increase the signal-to-noise ratio of our samples’ spectra through a process known as coaddition. We utilize spectroscopic absorption lines to determine the age and metallicity of our orphan GCs through comparison to stellar population synthesis models, which we then relate to the GCs’ original parent galaxies using a mass-metallicity relation. Our finding that remote GCs of M87 likely developed in galaxies with ~1010 solar masses implies that M87’s outer halo is formed of relatively massive galaxies, serving as important parameters for developing theories about the formation and evolution of massive galaxies.This research was funded in part by NASA/STScI and the National Science Foundation. Most of this work was carried out by high school students working under the auspices of the Science Internship Program at UC Santa Cruz.

Neutralization of B. anthracis toxins during ex vivo phagocytosis.

PubMed

Tarasenko, Olga; Scott, Ashley; Jones, April; Soderberg, Lee; Alusta, Pierre

2013-07-01

Glycoconjugates (GCs) are recognized as stimulation and signaling agents, affecting cell adhesion, activation, and growth of living organisms. Among GC targets, macrophages are considered ideal since they play a central role in inflammation and immune responses against foreign agents. In this context, we studied the effects of highly selective GCs in neutralizing toxin factors produced by B. anthracis during phagocytosis using murine macrophages. The effects of GCs were studied under three conditions: A) prior to, B) during, and C) following exposure of macrophages to B. anthracis individual toxin (protective antigen [PA], edema factor [EF], lethal factor [LF] or toxin complexes (PA-EF-LF, PA-EF, and PA-LF). We employed ex vivo phagocytosis and post-phagocytosis analysis including direct microscopic observation of macrophage viability, and macrophage activation. Our results demonstrated that macrophages are more prone to adhere to GC-altered PA-EF-LF, PA-EF, and PA-LF toxin complexes. This adhesion results in a higher phagocytosis rate and toxin complex neutralization during phagocytosis. In addition, GCs enhance macrophage viability, activate macrophages, and stimulate nitric oxide (NO) production. The present study may be helpful in identifying GC ligands with toxin-neutralizing and/or immunomodulating properties. In addition, our study could suggest GCs as new targets for existing vaccines and the prospective development of vaccines and immunomodulators used to combat the effects of B. anthracis.

Prevalence of graduated compression stocking-associated pressure injuries in surgical intensive care units.

PubMed

Hobson, Deborah B; Chang, Tracy Y; Aboagye, Jonathan K; Lau, Brandyn D; Shihab, Hasan M; Fisher, Betsy; Young, Samantha; Sujeta, Nancy; Shaffer, Dauryne L; Popoola, Victor O; Kraus, Peggy S; Knorr, Gina; Farrow, Norma E; Streiff, Michael B; Haut, Elliott R

2017-08-01

This study aimed to determine the prevalence of static graduated compression stocking (sGCS)-associated pressure injury among patients in surgical intensive care units (ICUs). We retrospectively reviewed data from wound care rounds between April 2011 and June 2012 at 3 surgical ICUs at an urban, tertiary care hospital. Patients with sGCS-associated pressure injury were identified and descriptive analysis was performed on their demographic, perioperative, and postoperative characteristics. We examined 1787 individual patients during 2391 patient encounters. A total of 129 (7.2%) of patients developed pressure injuries. Forty patients (2.2%) developed sGCS-associated pressure injury. Static GCS-associated pressure injury accounted for 31% (40/129) of all pressure injuries and 74% (40/54) of all medical device-related pressure injury. Eighteen (45%) and 6 (15%) developed stage 1 and 2 pressure injury, respectively, and 16 (40%) developed deep tissue injuries. The mean age of our patients was 64.7 years, about half (47.5%) were male, and their mean Acute Physiology and Chronic Health Evaluation II score was 18.8. Many had comorbid conditions, including obesity (44.5%) and diabetes (42.5%), and required mechanical ventilation (45%). Pressure injuries are a notable complication of sGCS in surgical ICU patients. Appropriate measures are required to help avoid this potentially preventable harm. Copyright © 2017 Elsevier Inc. All rights reserved.

α-fetoprotein involvement during glucocorticoid-induced precocious maturation in rat colon

PubMed Central

Chen, Min; Sun, Peng; Liu, Xiao-Yan; Dong, Dan; Du, Jun; Gu, Luo; Ge, Ying-Bin

2011-01-01

AIM: To investigate the role of α-fetoprotein (AFP), a cancer-associated fetal glycoprotein, in glucocorticoid-induced precocious maturation in rat colon. METHODS: Colons from suckling Sprague-Dawley rats were used in this study. Corticosterone acetate at a dose of 100 μg/g body weight was given to normal pups on days 7, 9 and 11 after birth to induce hypercorticoidism. Control animals were injected with identical volumes of normal saline. Some rats receiving corticosterone 7 d after birth were also treated with mifepristone (RU38486), a glucocorticoid cytoplasm receptor antagonist to investigate the effects of glucocorticoids (GCs). The morphological changes of the crypt depth and villous height of the villous zone in colon were observed as indices of colon maturation. Expression levels of AFP in colons were detected by reverse transcriptase polymerase chain reaction and Western blotting. To identify the cellular localization of AFP in developing rat colons, double-immunofluorescent staining was performed using antibodies to specific mesenchymal cell marker and AFP. RESULTS: Corticosterone increased the crypt depth and villous height in the colon of 8- and 10-d-old rats with hypercorticoidism compared with that in the control animals (120% in 8-d-old rats and 118% in 10-d-old rats in villous height, P = 0.021; 145% in 8-d-old rats and 124% in 10-d-old rats in crypt depth, P = 0.017). These increases were accompanied by an increase of AFP expression in both mRNA and protein (2.5-folds in 8-d-old and 2.5-folds in 10-d-old rats higher than in control animals, P = 0.035; 1.8-folds in 8-d-old and 1.3-folds in 10-d-old rats higher than in control animals, P = 0.023). Increased crypt depth and villous height and increased expression of AFP in the colon of rats with hypercorticoidism were blocked by mifepristone. Both had positive staining for AFP or vimentin, and overlapped in mesenchymal cells at each tested colon. CONCLUSION: GCs promote the development of rat colon. AFP appears to be involved, in part, in mediating the effects of GCs in the developmental colon. PMID:21734804

Generalized chaos synchronization theorems for bidirectional differential equations and discrete systems with applications

NASA Astrophysics Data System (ADS)

Ji, Ye; Liu, Ting; Min, Lequan

2008-05-01

Two constructive generalized chaos synchronization (GCS) theorems for bidirectional differential equations and discrete systems are introduced. Using the two theorems, one can construct new chaos systems to make the system variables be in GCS. Five examples are presented to illustrate the effectiveness of the theoretical results.

Delayed Traumatic Intracranial Haemorrhage and Progressive Traumatic Brain Injury in a Major Referral Centre Based in a Developing Country

PubMed Central

Jeng, Toh Charng; Haspani, Mohd Saffari Mohd; Adnan, Johari Siregar; Naing, Nyi Nyi

2008-01-01

A repeat Computer Tomographic (CT) brain after 24–48 hours from the 1st scanning is usually practiced in most hospitals in South East Asia where intracranial pressure monitoring (ICP) is routinely not done. This interval for repeat CT would be shortened if there was a deterioration in Glasgow Coma Scale (GCS). Most of the time the prognosis of any intervention may be too late especially in hospitals with high patient-to-doctor ratio causing high mortality and morbidity. The purpose of this study was to determine the important predictors for early detection of Delayed Traumatic Intracranial Haemorrhage (DTICH) and Progressive Traumatic Brain Injury (PTBI) before deterioration of GCS occurred, as well as the most ideal timing of repeated CT brain for patients admitted in Malaysian hospitals. A total of 81 patients were included in this study over a period of six months. The CT scan brain was studied by comparing the first and second CT brain to diagnose the presence of DTICH/PTBI. The predictors tested were categorised into patient factors, CT brain findings and laboratory investigations. The mean age was 33.1 ± 15.7 years with a male preponderance of 6.36:1. Among them, 81.5% were patients from road traffic accidents with Glasgow Coma Scale ranging from 4 – 15 (median of 12) upon admission. The mean time interval delay between trauma and first CT brain was 179.8 ± 121.3 minutes for the PTBI group. The DTICH group, 9.9% of the patients were found to have new intracranial clots. Significant predictors detected were different referral hospitals (p=0.02), total GCS status (p=0.026), motor component of GCS (p=0.043), haemoglobin level (p<0.001), platelet count (p=0.011) and time interval between trauma and first CT brain (p=0.022). In the PTBI group, 42.0% of the patients were found to have new changes (new clot occurrence, old clot expansion and oedema) in the repeat CT brain. Univariate statistical analysis revealed that age (p=0.03), race (p=0.035), types of admission (p=0.024), GCS status (p=0.02), pupillary changes (p=0.014), number of intracranial lesion (p=0.004), haemoglobin level (p=0.038), prothrombin time (p=0.016) as the best predictors of early detection of changes. Multiple logistics regression analysis indicated that age, severity, GCS status (motor component) and GCS during admission were significantly associated with second CT scan with changes. This study showed that 9.9% of the total patients seen in the period of study had DTICH and 42% had PTBI. In the early period after traumatic head injury, the initial CT brain did not reveal the full extent of haemorrhagic injury and associated cerebral oedema. Different referral hospitals of different trauma level, GCS status, motor component of the GCS, haemoglobin level, platelet count and time interval between trauma and the first CT brain were the significant predictors for DTICH. Whereas the key determinants of PTBI were age, race, types of admission, GCS status, pupillary changes, number of intracranial bleed, haemoglobin level, prothrombin time and of course time interval between trauma and first CT brain. Any patients who had traumatic head injury in hospitals with no protocol of repeat CT scan or intracranial pressure monitoring especially in developing countries are advised to have to repeat CT brain at the appropriate quickest time . PMID:22589639

Causal Evidence for the Role of Specific GABAergic Interneuron Types in Entorhinal Recruitment of Dentate Granule Cells

PubMed Central

Lee, Cheng-Ta; Kao, Min-Hua; Hou, Wen-Hsien; Wei, Yu-Ting; Chen, Chin-Lin; Lien, Cheng-Chang

2016-01-01

The dentate gyrus (DG) is the primary gate of the hippocampus and controls information flow from the cortex to the hippocampus proper. To maintain normal function, granule cells (GCs), the principal neurons in the DG, receive fine-tuned inhibition from local-circuit GABAergic inhibitory interneurons (INs). Abnormalities of GABAergic circuits in the DG are associated with several brain disorders, including epilepsy, autism, schizophrenia, and Alzheimer disease. Therefore, understanding the network mechanisms of inhibitory control of GCs is of functional and pathophysiological importance. GABAergic inhibitory INs are heterogeneous, but it is unclear how individual subtypes contribute to GC activity. Using cell-type-specific optogenetic perturbation, we investigated whether and how two major IN populations defined by parvalbumin (PV) and somatostatin (SST) expression, regulate GC input transformations. We showed that PV-expressing (PV+) INs, and not SST-expressing (SST+) INs, primarily suppress GC responses to single cortical stimulation. In addition, these two IN classes differentially regulate GC responses to θ and γ frequency inputs from the cortex. Notably, PV+ INs specifically control the onset of the spike series, whereas SST+ INs preferentially regulate the later spikes in the series. Together, PV+ and SST+ GABAergic INs engage differentially in GC input-output transformations in response to various activity patterns. PMID:27830729

Predictions of Gamma-ray Emission from Globular Cluster Millisecond Pulsars Above 100 MeV

NASA Technical Reports Server (NTRS)

Venter, C.; de Jaker, O.C.; Clapson, A.C.

2009-01-01

The recent Fermi detection of the globular cluster (GC) 47 Tucanae highlighted the importance of modeling collective gamma-ray emission of millisecond pulsars (MSPs) in GCs. Steady flux from such populations is also expected in the very high energy (VHE) domain covered by ground-based Cherenkov telescopes. We present pulsed curvature radiation (CR) as well as unpulsed inverse Compton (IC) calculations for an ensemble of MSPs in the GCs 47 Tucanae and Terzan 5. We demonstrate that the CR from these GCs should be easily detectable for Fermi, while constraints on the total number of MSps and the nebular B-field may be derived using the IC flux components.

DO INTERMEDIATE-MASS BLACK HOLES EXIST IN GLOBULAR CLUSTERS?

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

Sun, Mou-Yuan; Jin, Ya-Ling; Gu, Wei-Min

2013-10-20

The existence of intermediate-mass black holes (IMBHs) in globular clusters (GCs) remains a crucial problem. Searching for IMBHs in GCs reveals a discrepancy between radio observations and dynamical modelings: the upper mass limits constrained by radio observations are systematically lower than that of dynamical modelings. One possibility for such a discrepancy is that, as we suggest in this work, there exist outflows in accretion flows. Our results indicate that, for most sources, current radio observations cannot rule out the possibility that IMBHs may exist in GCs. In addition, we adopt an M-dot -L{sub R} relation to revisit this issue, whichmore » confirms the results obtained by the fundamental plane relation.« less

Flexible Delivery as a "Whole-Organisation": What Does This Mean in Practice?

ERIC Educational Resources Information Center

Henry, John; Wakefield, Lyn

A research project called Support Services for Flexible Delivery was commissioned by the Australian organization TAFE (technical and further education) Frontiers. Since 1995, the project has been conducted by using a research approach called the Generalizations from Case Studies (GCS) research method. The GCS method was developed, tested, and…

Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular dystrophy through a defined metabolic program.

PubMed

Morrison-Nozik, Alexander; Anand, Priti; Zhu, Han; Duan, Qiming; Sabeh, Mohamad; Prosdocimo, Domenick A; Lemieux, Madeleine E; Nordsborg, Nikolai; Russell, Aaron P; MacRae, Calum A; Gerber, Anthony N; Jain, Mukesh K; Haldar, Saptarsi M

2015-12-08

Classic physiology studies dating to the 1930s demonstrate that moderate or transient glucocorticoid (GC) exposure improves muscle performance. The ergogenic properties of GCs are further evidenced by their surreptitious use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dystrophy (DMD), a genetic muscle-wasting disease. A defined molecular basis underlying these performance-enhancing properties of GCs in skeletal muscle remains obscure. Here, we demonstrate that ergogenic effects of GCs are mediated by direct induction of the metabolic transcription factor KLF15, defining a downstream pathway distinct from that resulting in GC-related muscle atrophy. Furthermore, we establish that KLF15 deficiency exacerbates dystrophic severity and muscle GC-KLF15 signaling mediates salutary therapeutic effects in the mdx mouse model of DMD. Thus, although glucocorticoid receptor (GR)-mediated transactivation is often associated with muscle atrophy and other adverse effects of pharmacologic GC administration, our data define a distinct GR-induced gene regulatory pathway that contributes to therapeutic effects of GCs in DMD through proergogenic metabolic programming.

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

Dalessandro, E.; Lapenna, E.; Mucciarelli, A.

We used a combination of optical and near-UV Hubble Space Telescope photometry and FLAMES/ESO-VLT high-resolution spectroscopy to characterize the stellar content of the old and massive globular cluster (GC) NGC 121 in the Small Magellanic Cloud (SMC). We report on the detection of multiple stellar populations, the first case in the SMC stellar cluster system. This result enforces the emerging scenario in which the presence of multiple stellar populations is a distinctive-feature of old and massive GCs regardless of the environment, as far as the light-element distribution is concerned. We find that second-generation (SG) stars are more centrally concentrated thanmore » first-generation (FG) ones. More interestingly, at odds with what is typically observed in Galactic GCs, we find that NGC 121 is the only cluster so far to be dominated by FG stars that account for more than 65% of the total cluster mass. In the framework where GCs were born with 90%–95% of FG stars, this observational finding would suggest that either NGC 121 experienced a milder stellar mass-loss with respect to Galactic GCs or it formed a smaller fraction of SG stars.« less

Three-dimensional culture of buffalo granulosa cells in hanging drop mimics the preovulatory follicle stage.

PubMed

Yadav, Monica; Agrawal, Himanshu; Pandey, Mamta; Singh, Dheer; Onteru, Suneel K

2018-03-01

Granulosa cell (GC) culture models mimicking the intrafollicular environment are limited. Such models have a great potential in reproductive toxicity studies. The buffalo, a monovulatory species like humans, could be a better model than polyovulatory rodents. Therefore, we targeted the development and characterization of three-dimensional (3D) culture systems for buffalo GCs. The GCs from small ovarian follicles (SF) maintained the CYP19 gene expression for 144 hr in a 2D culture system. Hence, GCs from SF were cultured directly in 3D using hanging drop and Poly-([2-hydroxyethyl methacrylate]) (polyHEMA) methods in the DMEM media containing 1 ng/ml FSH and 10 ng/ml IGF-1 for 144 hr. The expression profile of nine GC-specific transcripts; CYP19, TNFAIP6, AMH, PTI, NR4A1, FSHR, RUNX, LHR, and COX2/PTGS2; revealed that 3D-spheroids developed in hanging drop method maintained the GC phenotype of preovulatory follicles. Therefore, hanging drop method is a best method for culturing GCs to mimic the intrafollicular environment. © 2017 Wiley Periodicals, Inc.

Longitudinal course of eating disorders after transsexual treatment: a report of two cases.

PubMed

Hiraide, Maiko; Harashima, Saki; Yoneda, Ryo; Otani, Makoto; Kayano, Mami; Yoshiuchi, Kazuhiro

2017-01-01

Several reports have been published on patients with gender dysphoria and eating disorders. However, there have been few reports on the longitudinal course of eating disorders after gender reassignment surgery (GRS)/gender confirmation surgery (GCS). We report two Japanese cases of transsexual persons with eating disorders who underwent GRS/GCS, one male-to-female (MtF) and one female-to-male (FtM). Case 1 was a 35-year MtF person who had a 14-year-course of bulimia nervosa that developed after GRS. Case 2 was a 35-year FtM person with anorexia nervosa who underwent GCS 9 years before. We found that the treatment of our transsexual patients influenced the course of their eating disorders for a long period, which could be attributable partly to the cultural situation in Japan, an East Asian country. It is possible that many gender identity problems and identity problems in general persist even after surgery and treatment; therefore, continual clinical support should be provided for patients with gender dysphoria and eating disorders even after hormonal therapy or GRS/GCS.

Effect of glucocorticosteroid treatment on ovalbumin-induced IgE-mediated immediate and late allergic response in guinea pig.

PubMed

Andersson, P; Brange, C; von Kogerer, B; Sonmark, B; Stahre, G

1988-01-01

The effect of glucocorticosteroid (GCS) treatment on ovalbumine-induced IgE-mediated immediate and late allergic response was studied in sensitized guinea pigs. The results show that the GCS budesonide (BUD) inhibits the allergen-induced IgE-mediated immediate and late bronchial obstruction. The effect on the early reaction is correlated to the inhibition of leukotrienes and histamine release. The importance of mediator release inhibition for the antianaphylactic effect of GCS is discussed. In examining the effect on the late reaction, it was found that BUD had to be present during the early reaction but did not inhibit the early reaction. Furthermore, the effect on the late reaction was correlated to the inhibition of vascular leakage but not to the infiltration of inflammatory cells as examined in bronchoalveolar lavage. The results indicate that some triggering factors important for the development of the late reaction are released during the early reaction. Inhibition of the release of that factor or the activation of inflammatory cells by that factor might be the mechanism behind the antiinflammatory activities of GCS.

Interaction of glucocorticoids and progesterone derivatives with human serum albumin.

PubMed

Abboud, Rola; Akil, Mohammad; Charcosset, Catherine; Greige-Gerges, Hélène

2017-10-01

Glucocorticoids (GCs) and progesterone derivatives (PGDs) are steroid hormones with well-known biological activities. Their interaction with human serum albumin (HSA) may control their distribution. Their binding to albumin is poorly studied in literature. This paper deals with the interaction of a series of GCs (cortisol, cortisone, prednisolone, prednisone, 6-methylprednisolone and 9-fluorocortisol acetate) and PGDs (progesterone, hydroxylated PGDs, methylated PGDs and dydrogesterone) with HSA solution (pH 7.4) at molar ratios steroid to HSA varying from 0 to 10. Similar titrations were conducted using Trp aqueous solution. Fluorescence titration method and Fourier transform infrared spectroscopy (FTIR) are used. PGDs (except dydrogesterone), cortisone and 9-fluorocortisol acetate affected weakly the fluorescence of Trp in buffer solution while they decreased in a dose-dependent manner that of HSA. Their binding constants to HSA were then calculated. Moreover, displacement experiment was performed using bilirubin as a site marker. The binding constant of bilirubin to albumin was determined in the absence and presence of a steroid at a molar ratio steroid to HSA of 1. The results indicate that the steroids bind to HSA at site I in a pocket different from that of bilirubin. Furthermore, the peak positions of amide I and amide II bands of HSA were shifted in the presence of progesterone, dydrogesterone and GCs. Also a variation was observed in amide I region indicating the formation of hydrogen bonding between albumin and steroids. Copyright © 2017 Elsevier B.V. All rights reserved.

Variation in PPP3CC Genotype Is Associated with Long-Term Recovery after Severe Brain Injury.

PubMed

Osier, Nicole D; Bales, James W; Pugh, Bunny; Shin, Samuel; Wyrobek, Julie; Puccio, Ava M; Okonkwo, David O; Ren, Dianxu; Alexander, Sheila; Conley, Yvette P; Dixon, C Edward

2017-01-01

After experimental traumatic brain injury (TBI), calcineurin is upregulated; blocking calcineurin is associated with improved outcomes. In humans, variation in the calcineurin A-gamma gene (PPP3CC) has been associated with neuropsychiatric disorders, though any role in TBI recovery remains unknown. This study examines associations between PPP3CC genotype and mortality, as well as gross functional status assessed at admission using the Glasgow Coma Scale (GCS) and at 3, 6, and 12 months after severe TBI using the Glasgow Outcome Score (GOS). The following tagging single nucleotide polymorphisms (tSNPs) in PPP3CC were genotyped: rs2443504, rs2461491, rs2469749, and rs10108011. The rs2443504 AA genotype was univariately associated with GCS (p = 0.022), GOS at 3, 6, and 12 months (p = 0.002, p = 0.034, and p = 0.004, respectively), and mortality (p = 0.007). In multivariate analysis controlling for age, sex, and GCS, the AA genotype of rs2443504 was associated with GOS at 3 (p = 0.02), and 12 months (p = 0.01), with a trend toward significance at 6 months (p = 0.05); the AA genotype also was associated with mortality in the multivariate model (p = 0.04). Further work is warranted to better understand the role of calcineurin, as well as the genes encoding it and their relevance to outcomes after brain injury.

STAR FORMATION HISTORY OF THE MILKY WAY HALO TRACED BY THE OOSTERHOFF DICHOTOMY AMONG GLOBULAR CLUSTERS

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

Jang, Sohee; Lee, Young-Wook, E-mail: ywlee2@yonsei.ac.kr

2015-06-22

In our recent investigation of the Oosterhoff dichotomy in the multiple population paradigm, we have suggested that the RR Lyrae variables in the globular clusters (GCs) of Oosterhoff groups I, II, and III are produced mostly by first, second, and third generation stars (G1, G2, and G3), respectively. Here we show, for the first time, that the observed dichotomies in the inner and outer halo GCs can be naturally reproduced when these models are extended to all metallicity regimes, while maintaining reasonable agreements in the horizontal-branch type versus [Fe/H] correlations. In order to achieve this, however, specific star formation historiesmore » are required for the inner and outer halos. In the inner halo GCs, the star formation commenced and ceased earlier with a relatively short formation timescale between the subpopulations (∼0.5 Gyr), while in the outer halo, the formation of G1 was delayed by ∼0.8 Gyr with a more extended timescale between G1 and G2 (∼1.4 Gyr). This is consistent with the dual origin of the Milky Way halo. Despite the difference in detail, our models show that the Oosterhoff period groups observed in both outer and inner halo GCs are all manifestations of the “population-shift” effect within the instability strip, for which the origin can be traced back to the two or three discrete episodes of star formation in GCs.« less

Gemini Spectra of Star Clusters in the Spiral Galaxy M101

NASA Astrophysics Data System (ADS)

Simanton-Coogan, Lesley A.; Chandar, Rupali; Miller, Bryan; Whitmore, Bradley C.

2017-12-01

We present low resolution, visible light spectra of 41 star clusters in the spiral galaxy M101, taken with the Gemini/GMOS instrument. We measure Lick indices for each cluster and compare with BaSTI models to estimate their ages and metallicities. We also measure the line-of-sight velocities. We find that 25 of the clusters are fairly young massive clusters (YMCs) with ages of hundreds of millions of years, and 16 appear to be older, globular clusters (GCs). There are at least four GCs with best-fit ages of ≈1–3 Gyr and eight with best-fit ages of ≈5–10 Gyr. The mean metallicity of the YMCs is [Fe/H] ≈ ‑0.1 and for the GCs is [Fe/H] ≈ ‑0.9. We find a near-continuous spread in both age and metallicity for our sample, which may indicate that M101 had a more-or-less continuous history of cluster and star formation. From the kinematics, we find that the YMCs rotate with the H I gas fairly well, while the GCs do not. We cannot definitively say whether the GCs sampled here lie in an inner halo, thick disk, or bulge/psuedobulge component, although given the very small bulge in M101, the last seems unlikely. The kinematics and ages of the YMCs suggest that M101 may have undergone heating of its disk or possibly a continuous merger/accretion history for the galaxy.

K2 and M4: A Unique Opportunity to Unlock the Mysteries of Globular Clusters

NASA Astrophysics Data System (ADS)

Kuehn, Charles A.; Stello, Dennis; Campbell, Simon; Drury, Jason; de Silva, Gayandhi; Maclean, Ben; Bedding, Timothy R.; Huber, Daniel

2016-01-01

One of the most exciting opportunities presented by K2 is the ability to study variable stars in globular clusters (GCs). The K2 observations allow us to perform ensemble asteroseismology of a population that is much older than that in the open clusters in the original Kepler field. This should help us answer long-standing questions concerning mass loss on the red giant branch and the spread in masses along the horizontal branch. By combining the asteroseismic data with chemical tagging of sub-populations from spectroscopy, we hope to better constrain stellar evolution models and potentially shed some light on the formation history of GCs. The very crowded nature of stars in GCs poses a challenge, however, due to Kepler's large pixels. M4, observed during K2's campaign 2, presents an excellent opportunity to study GCs with a combination of K2 and ground-based data. M4 is one of the two nearest GCs and thus should appear less crowded and brighter; in fact M4 is likely the only GC whose horizontal branch stars, other than RR Lyraes, will be accessible with K2. We discuss our method of obtaining photometry for the stars in M4 and present sample lightcurves for different classes of oscillating stars in the cluster. We also discuss efforts to use ground-based observations to increase the utility of the K2 dataset.

Luteogenic Hormones Act through a Vascular Endothelial Growth Factor-Dependent Mechanism to Up-Regulate α5β1 and αvβ3 Integrins, Promoting the Migration and Survival of Human Luteinized Granulosa Cells

PubMed Central

Rolaki, Alexandra; Coukos, George; Loutradis, Dimitris; DeLisser, Horace M.; Coutifaris, Christos; Makrigiannakis, Antonis

2007-01-01

The formation of the corpus luteum (CL) is critical for the establishment of a successful pregnancy. After ovulation, the CL develops from the remnants of the ovulated ovarian follicle. This process, which involves varying cell-matrix interactions, is poorly characterized. To understand the role and potential regulation of cell-matrix interactions in the formation of the CL, we investigated the expression and activity of the matrix protein fibronectin (FN) and several of its integrin receptors on luteinized granulosa cells (GCs). In situ, FN and several FN-binding integrins were detected around luteinizing GCs during the early luteal phase, although expression declined in the late luteal phase. In vitro, GCs released FN, and stimulation of these cells with human chorionic gonadotropin increased the surface expression of FN, α5β1, and αvβ3. Up-regulation of these proteins on GCs was reproduced by stimulation with vascular endothelial growth factor (VEGF) and was inhibited by anti-VEGF antibody. Lastly, expression of α5β1 and αvβ3 mediated adhesion to FN, facilitated migration, and prevented apoptosis. These data suggest that in vivo luteogenic hormones, in part through a VEGF-dependent mechanism, stimulate selected integrin-matrix adhesive interactions that promote the motility and survival of GCs and thus contribute to the formation and preservation of the CL. PMID:17456762

Optimal therapy and prospects for new medicines in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

PubMed

Pagnoux, Christian; Groh, Matthieu

2016-10-01

The prevalence of eosinophilic granulomatosis with polyangiitis (EGPA; previously known as Churg-Strauss syndrome) is lower than that of other antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV's), and only a few randomized controlled trials have been conducted for this rare disease. However, recent international efforts have helped delineate the best treatment approach. At present, EGPA conventional therapy is by default similar to that of other AAVs. Limited, non-severe EGPA can initially be treated with glucocorticoids (GCs) alone. Patients with life-threatening manifestations and/or major organ involvement must receive a combination of GCs and an immunosuppressant, mainly cyclophosphamide. Remission can be achieved in >85% of patients with these first-line treatments, but vasculitis relapses occur in more than one-third of patients, and about 85% cannot stop GC treatment because of GC-dependent asthma and/or ENT manifestations. A few biologic agents, including rituximab or mepolizumab, are now under investigation after interesting preliminary results. Expert commentary: Treatment for EGPA still has several unmet needs. Several biologic agents are now under investigation in randomized controlled trials, but a few others should be considered soon. Their benefit should be demonstrated for devising more EGPA-tailored therapeutic strategies (ideally GC-free).

Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke

PubMed Central

Lorente, Leonardo; Martín, María M.; Almeida, Teresa; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Riaño-Ruiz, Marta; Solé-Violán, Jordi; Hernández, Mariano

2016-01-01

Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541–18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke. PMID:27338372

FOUR Score Predicts Early Outcome in Patients After Traumatic Brain Injury.

PubMed

Nyam, Tee-Tau Eric; Ao, Kam-Hou; Hung, Shu-Yu; Shen, Mei-Li; Yu, Tzu-Chieh; Kuo, Jinn-Rung

2017-04-01

The aim of the study was to determine whether the Full Outline of UnResponsiveness (FOUR) score, which includes eyes opening (E), motor function (M), brainstem reflex (B), and respiratory pattern (R), can be used as an alternate method to the Glasgow Coma Scale (GCS) in predicting intensive care unit (ICU) mortality in traumatic brain injury (TBI) patients. From January 2015 to June 2015, patients with isolated TBI admitted to the ICU were enrolled. Three advanced practice nurses administered the FOUR score, GCS, Acute Physiology and Chronic Health Evaluation II (APACHE II), and Therapeutic Intervention Scoring System (TISS) concurrently from ICU admissions. The endpoint of observation was mortality when the patients left the ICU. Data are presented as frequency with percentages, mean with standard deviation, or median with interquartile range. Each measurement tool used area under the receiver operating characteristic curve to compare the predictive power between these four tools. In addition, the difference between survival and death was estimated using the Wilcoxon rank sum test. From 55 TBI patients, males (72.73 %) were represented more than females, the mean age was 63.1 ± 17.9, and 19 of 55 observations (35 %) had a maximum FOUR score of 16. The overall mortality rate was 14.6 %. The area under the receiver operating characteristic curve was 74.47 % for the FOUR score, 74.73 % for the GCS, 81.78 % for the APACHE II, and 53.32 % for the TISS. The FOUR score has similar predictive power of mortality compared to the GCS and APACHE II. Each of the parameters-E, M, B, and R-of the FOUR score showed a significant difference between mortality and survival group, while the verbal and eye-opening components of the GCS did not. Having similar predictive power of mortality compared to the GCS and APACHE II, the FOUR score can be used as an alternative in the prediction of early mortality in TBI patients in the ICU.

Glucocorticoids and laminitis in the horse.

PubMed

Johnson, Philip J; Slight, Simon H; Ganjam, Venkataseshu K; Kreeger, John M

2002-08-01

The administration of exogenously administered GCs and syndromes associated with GC excess are both attended by increased risk for the development of laminitis in adult horses. However, there exists substantial controversy as to whether excess GCs cause laminitis de novo. If true, the pathogenesis of laminitis arising from the effects of GC excess is probably different from that associated with diseases of the gastrointestinal tract and endotoxemia. Although a satisfactory explanation for the development of laminitis as a consequence of GC action is currently lacking, numerous possible and plausible theoretical mechanisms do exist. Veterinarians must exert caution with respect to the use of GCs in adult horses. The extent to which individual horses are predisposed to laminitis as a result of GC effect cannot be predicted based on current information. However, the administration of systemic GCs to horses that have been previously affected by laminitis should be used only with extreme caution, and should be accompanied by careful monitoring for further signs of laminitis. The risk of laminitis appears to be greater during treatment using some GCs (especially dexamethasone and triamcinalone) compared with others (prednisone and prednisolone). Whenever possible, to reduce the risk of laminitis, GCs should be administered locally. For example, the risk of GC-associated laminitis is evidently considerably reduced in horses affected with chronic obstructive pulmonary disease (COPD) if GC treatment is administered via inhalation. We have hypothesized that structural changes in the equine hoof that resemble laminitis may arise as a consequence of excess GC effect. Although these changes are not painful per se, and are not associated with inflammation, they could likely predispose affected horses to the development of bona fide laminitis for other reasons. Moreover, the gross morphological appearance of the chronically GC-affected hoof resembles that of a chronically foundered hoof in some respects. Further investigation into the effect of GC on the hoof lamellar interface is clearly needed.

Signalling mechanism for somatostatin receptor 5-mediated suppression of AMPA responses in rat retinal ganglion cells.

PubMed

Deng, Qin-Qin; Sheng, Wen-Long; Zhang, Gong; Weng, Shi-Jun; Yang, Xiong-Li; Zhong, Yong-Mei

2016-08-01

Somatostatin (SRIF) is involved in a variety of physiological functions via the activation of five subtypes of specific receptors (sst1-5). Here, we investigated the effects of SRIF on AMPA receptor (AMPAR)-mediated currents (AMPA currents) in isolated rat retinal ganglion cells (GCs) using patch-clamp techniques. Immunofluorescence double labelling demonstrated the expression of sst5 in rat GCs. Consistent to this, whole cell AMPA currents of GCs were dose-dependently suppressed by SRIF, and the effect was reversed by the sst5 antagonist BIM-23056. Intracellular dialysis of GDP-β-S or pre-incubation with the Gi/o inhibitor pertussis toxin (PTX) abolished the SRIF effect. The SRIF effect was mimicked by the administration of either 8-Br-cAMP or forskolin, but was eliminated by the protein kinase A (PKA) antagonists H-89/KT5720/Rp-cAMP. Moreover, SRIF increased intracellular Ca(2+) levels and did not suppress the AMPA currents when GCs were infused with an intracellular Ca(2+)-free solution or in the presence of ryanodine receptor modulators caffeine/ryanodine. Furthermore, the SRIF effect was eliminated when the activity of calmodulin (CaM), calcineurin and protein phosphatase 1 (PP1) was blocked with W-7, FK-506 and okadaic acid, respectively. SRIF persisted to suppress the AMPA currents when cGMP-protein kinase G (PKG) and phosphatidylinositol (PI)-/phosphatidylcholine (PC)-phospholipase C (PLC) signalling pathways were blocked. In rat flat-mount retinas, SRIF suppressed AMPAR-mediated light-evoked excitatory postsynaptic currents (L-EPSCs) in GCs. We conclude that a distinct Gi/o/cAMP-PKA/ryanodine/Ca(2+)/CaM/calcineurin/PP1 signalling pathway comes into play due to the activation of sst5 to mediate the SRIF effect on GCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of the Modified Glasgow Coma Scale Score Criteria for Mild Traumatic Brain Injury on Mortality Prediction: Comparing Classic and Modified Glasgow Coma Scale Score Model Scores of 13

PubMed Central

Mena, Jorge Humberto; Sanchez, Alvaro Ignacio; Rubiano, Andres M.; Peitzman, Andrew B.; Sperry, Jason L.; Gutierrez, Maria Isabel; Puyana, Juan Carlos

2011-01-01

Objective The Glasgow Coma Scale (GCS) classifies Traumatic Brain Injuries (TBI) as Mild (14–15); Moderate (9–13) or Severe (3–8). The ATLS modified this classification so that a GCS score of 13 is categorized as mild TBI. We investigated the effect of this modification on mortality prediction, comparing patients with a GCS of 13 classified as moderate TBI (Classic Model) to patients with GCS of 13 classified as mild TBI (Modified Model). Methods We selected adult TBI patients from the Pennsylvania Outcome Study database (PTOS). Logistic regressions adjusting for age, sex, cause, severity, trauma center level, comorbidities, and isolated TBI were performed. A second evaluation included the time trend of mortality. A third evaluation also included hypothermia, hypotension, mechanical ventilation, screening for drugs, and severity of TBI. Discrimination of the models was evaluated using the area under receiver operating characteristic curve (AUC). Calibration was evaluated using the Hoslmer-Lemershow goodness of fit (GOF) test. Results In the first evaluation, the AUCs were 0.922 (95 %CI, 0.917–0.926) and 0.908 (95 %CI, 0.903–0.912) for classic and modified models, respectively. Both models showed poor calibration (p<0.001). In the third evaluation, the AUCs were 0.946 (95 %CI, 0.943 – 0.949) and 0.938 (95 %CI, 0.934 –0.940) for the classic and modified models, respectively, with improvements in calibration (p=0.30 and p=0.02 for the classic and modified models, respectively). Conclusion The lack of overlap between ROC curves of both models reveals a statistically significant difference in their ability to predict mortality. The classic model demonstrated better GOF than the modified model. A GCS of 13 classified as moderate TBI in a multivariate logistic regression model performed better than a GCS of 13 classified as mild. PMID:22071923

Vitamin D receptor expression and potential role of vitamin D on cell proliferation and steroidogenesis in goat ovarian granulosa cells.

PubMed

Yao, Xiaolei; Zhang, Guomin; Guo, Yixuan; Ei-Samahy, Mohamed; Wang, Shuting; Wan, Yongjie; Han, Le; Liu, Zifei; Wang, Feng; Zhang, Yanli

2017-10-15

This study aimed to investigate the expression of the vitamin D receptor (VDR) in goat follicles and to determine the effects of Vit D 3 supplementation on goat granulosa cells (GCs) function linked to follicular development. The results demonstrated that VDR was prominently localized in GCs, with expression increasing with follicle diameter. Addition of Vit D 3 (1α,25-(OH) 2 VD 3 ; 10 nM) to GCs caused an increase in VDR and in steroidogenic acute regulator (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA expression. Additionally, Vit D 3 increased the cyclic adenosine monophosphate (cAMP), estradiol (E 2 ), and progesterone (P 4 ) levels, while it decreased anti-müllerian hormone receptor (AMHR) and follicle-stimulating hormone receptor (FSHR) mRNA expression (P < 0.05). Addition of FSH remarkably increased E 2, P 4 , and cAMP levels (P < 0.05), and Vit D 3 further enhanced the E 2 and cAMP levels in the presence of FSH (P < 0.05). Vit D 3 significantly induced the mRNA expression of CDK4 and CyclinD1, and downregulated P21 gene expression (P < 0.05). In addition, Vit D 3 significantly decreased reactive oxygen species (ROS) production and increased the mRNA and protein expression of superoxide dismutase 2 (SOD2) and catalase (CAT) (P < 0.05). In conclusion, VDR is expressed in GCs of the goat ovaries and Vit D 3 might play an important role in GCs proliferation by regulating cellular oxidative stress and cell cycle-related genes. Meanwhile, Vit D 3 enhances the E 2 and P 4 output of GCs by regulating the expression of 3β-HSD and StAR and the level of cAMP, which regulate steroidogenesis, supporting a potential role for Vit D 3 in follicular development. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of unseen assumptions on communication of atmospheric carbon mitigation options

NASA Astrophysics Data System (ADS)

Elliot, T. R.; Celia, M. A.; Court, B.

2010-12-01

With the rapid access and dissemination of information made available through online and digital pathways, there is need for a concurrent openness and transparency in communication of scientific investigation. Even with open communication it is essential that the scientific community continue to provide impartial result-driven information. An unknown factor in climate literacy is the influence of an impartial presentation of scientific investigation that has utilized biased base-assumptions. A formal publication appendix, and additional digital material, provides active investigators a suitable framework and ancillary material to make informed statements weighted by assumptions made in a study. However, informal media and rapid communiqués rarely make such investigatory attempts, often citing headline or key phrasing within a written work. This presentation is focused on Geologic Carbon Sequestration (GCS) as a proxy for the wider field of climate science communication, wherein we primarily investigate recent publications in GCS literature that produce scenario outcomes using apparently biased pro- or con- assumptions. A general review of scenario economics, capture process efficacy and specific examination of sequestration site assumptions and processes, reveals an apparent misrepresentation of what we consider to be a base-case GCS system. The authors demonstrate the influence of the apparent bias in primary assumptions on results from commonly referenced subsurface hydrology models. By use of moderate semi-analytical model simplification and Monte Carlo analysis of outcomes, we can establish the likely reality of any GCS scenario within a pragmatic middle ground. Secondarily, we review the development of publically available web-based computational tools and recent workshops where we presented interactive educational opportunities for public and institutional participants, with the goal of base-assumption awareness playing a central role. Through a series of interactive ‘what if’ scenarios, workshop participants were able to customize the models, which continue to be available from the Princeton University Subsurface Hydrology Research Group, and develop a better comprehension of subsurface factors contributing to GCS. Considering that the models are customizable, a simplified mock-up of regional GCS scenarios can be developed, which provides a possible pathway for informal, industrial, scientific or government communication of GCS concepts and likely scenarios. We believe continued availability, customizable scenarios, and simplifying assumptions are an exemplary means to communicate the possible outcome of CO2 sequestration projects; the associated risk; and, of no small importance, the consequences of base assumptions on predicted outcome.

Randomized Controlled Crossover Trial Comparing the Impact of Sham or Intranasal Tear Neurostimulation on Conjunctival Goblet Cell Degranulation.

PubMed

Gumus, Koray; Schuetzle, Karri L; Pflugfelder, Stephen C

2017-05-01

The aim of the study was to investigate the effects of the Allergan Intranasal Tear Neurostimulator (ITN) on conjunctival goblet cell (GC) degranulation. A randomized, double-masked, placebo-controlled crossover trial. A total of 15 subjects (5 normal and 10 dry eye) were enrolled in a 3-visit study consisting of 1 screening and 2 separate randomized-masked ITN treatments (sham extranasal or intranasal). Tear meniscus height (TMH) was measured by anterior segment optical coherence tomography before and after applications. Impression cytology (IC) was taken from the bulbar conjunctiva of the right eye for periodic acid-Schiff staining and from the left eye for MUC5AC mucin immunostaining at baseline and after each treatment. The ratio of degranulated to nondegranulated GCs was measured as a marker of secretion. In all participants, both inferior bulbar (IB) and temporal bulbar (TB) cytology specimens stained for MUC5AC revealed a significantly higher ratio of degranulated to nondegranulated GCs after the ITN (IB: 2.28 ± 1.27 and TB: 1.81 ± 1.01) compared to baseline (IB: 0.56 ± 0.55, P = .015) (TB: 0.56 ± 0.32, P = .003) and extranasal sham application (IB: 0.37 ± 0.29, P = .001) (TB: 0.39 ± 0.33, P = .001). When the same analysis was repeated in the dry eye or control groups, the ratio was significantly higher after ITN than the baseline ratio and ratio after extranasal application in both groups (P < .05). Moreover, although control subjects had a higher ratio of degranulated to nondegranulated GCs at baseline (0.75 ± 0.52) compared with the dry eye group (0.41 ± 0.27), the ratio became slightly higher in dry eye (2.04 ± 1.12 vs 1.99 ± 1.21 in control) after the ITN application. There was no significant difference between the IB or TB conjunctiva locations in terms of the effectiveness of the ITN application on conjunctival goblet cell secretory response. These preliminary results document that the Allergan ITN can stimulate degranulation of goblet cells in the conjunctiva, which is a promising new approach for the management of dry eye. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Backend Control Processor for a Multi-Processor Relational Database Computer System.

DTIC Science & Technology

1984-12-01

SCHOOL OF ENGI. UNCRSIFID MPONTIFF DEC 84 AFXT/GCS/ENG/84D-22 F/O 9/2 L ommhhhhmhhml mhhhommhhhhhm i-2 8 -- U0. 11111= Q. 2 111.8IIII- 1111111..6...THESIS Presented to the Faculty of the School of Engineering of the Air Force Institute of Technology Air University In Partial Fulfillment of the...development of a Backend Multi-Processor Relational Database Computer System. This thesis addresses a single component of this system, the Backend Control

Dietary 2-oxoglutarate prevents bone loss caused by neonatal treatment with maximal dexamethasone dose

PubMed Central

Tomaszewska, Ewa; Muszyński, Siemowit; Blicharski, Tomasz; Pierzynowski, Stefan G

2017-01-01

Synthetic glucocorticoids (GCs) are widely used in the variety of dosages for treatment of premature infants with chronic lung disease, respiratory distress syndrome, allergies, asthma, and other inflammatory and autoimmune conditions. Yet, adverse effects such as glucocorticoid-induced osteoporosis and growth retardation are recognized. Conversely, 2-oxoglutarate (2-Ox), a precursor of glutamine, glutamate, and collagen amino acids, exerts protective effects on bone development. Our aim was to elucidate the effect of dietary administered 2-Ox on bone loss caused by neonatal treatment with clinically relevant maximal therapeutic dexamethasone (Dex) dose. Long bones of neonatal female piglets receiving Dex, Dex+2-Ox, or untreated were examined through measurements of mechanical properties, density, mineralization, geometry, histomorphometry, and histology. Selected hormones, bone turnover, and growth markers were also analyzed. Neonatal administration of clinically relevant maximal dose of Dex alone led to over 30% decrease in bone mass and the ultimate strength (P < 0.001 for all). The length (13 and 7% for femur and humerus, respectively) and other geometrical parameters (13–45%) decreased compared to the control (P < 0.001 for all). Dex impaired bone growth and caused hormonal imbalance. Dietary 2-Ox prevented Dex influence and vast majority of assessed bone parameters were restored almost to the control level. Piglets receiving 2-Ox had heavier, denser, and stronger bones; higher levels of growth hormone and osteocalcin concentration; and preserved microarchitecture of trabecular bone compared to the Dex group. 2-Ox administered postnatally had a potential to maintain bone structure of animals simultaneously treated with maximal therapeutic doses of Dex, which, in our opinion, may open up a new opportunity in developing combined treatment for children treated with GCs. Impact statement The present study has showed, for the first time, that dietary 2-oxoglutarate (2-Ox) administered postnatally has a potential to improve/maintain bone structure of animals simultaneously treated with maximal therapeutic doses of dexamethasone (Dex). It may open the new direction in searching and developing combined treatment for children treated with glucocorticoids (GCs) since growing group of children is exposed to synthetic GCs and adverse effects such as glucocorticoid-induced osteoporosis and growth retardation are recognized. Currently proposed combined therapies have numerous side effects. Thus, this study proposed a new direction in combined therapies utilizing dietary supplementation with glutamine derivative. Impairment caused by Dex in presented long bones animal model was prevented by dietary supplementation with 2-Ox and vast majority of assessed bone parameters were restored almost to the control level. These results support previous thesis on the regulatory mechanism of nutrient utilization regulated by glutamine derivatives and enrich the nutritional science. PMID:28178857

MicroRNAs and Glucocorticoid-Induced Apoptosis in Lymphoid Malignancies

PubMed Central

Sionov, Ronit Vogt

2013-01-01

The initial response of lymphoid malignancies to glucocorticoids (GCs) is a critical parameter predicting successful treatment. Although being known as a strong inducer of apoptosis in lymphoid cells for almost a century, the signaling pathways regulating the susceptibility of the cells to GCs are only partly revealed. There is still a need to develop clinical tests that can predict the outcome of GC therapy. In this paper, I discuss important parameters modulating the pro-apoptotic effects of GCs, with a specific emphasis on the microRNA world comprised of small players with big impacts. The journey through the multifaceted complexity of GC-induced apoptosis brings forth explanations for the differential treatment response and raises potential strategies for overcoming drug resistance. PMID:23431463

Imprinting the Fate of Antigen-Reactive B Cells through the Affinity of the B Cell Receptor

PubMed Central

O'Connor, Brian P.; Vogel, Laura A.; Zhang, Weijun; Loo, William; Shnider, Danielle; Lind, Evan F.; Ratliff, Michelle; Noelle, Randolph J.; Erickson, Loren D.

2010-01-01

Long-lived plasma cells (PCs) and memory B cells (Bmem) constitute the cellular components of enduring humoral immunity, whereas short-lived PCs that rapidly produce Ig correspond to the host's need for immediate protection against pathogens. In this study we show that the innate affinity of the BCR for Ag imprints upon naive B cells their differentiation fate to become short-or long-lived PCs and Bmem. Using BCR transgenic mice with varying affinities for Ag, naive B cells with high affinity lose their capacity to form germinal centers (GCs), develop neither Bmem nor long-lived PCs, and are destined to a short-lived PC fate. Moderate affinity interactions result in hastened GC responses, and differentiation to long-lived PCs, but Bmem remain extinct. In contrast, lower affinity interactions show tempered GCs, producing Bmem and affinity-matured, long-lived PCs. Thus, a continuum of elementary to comprehensive humoral immune responses exists that is controlled by inherent BCR affinity. PMID:17114443

Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks.

PubMed

Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

2018-05-01

Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic-pituitary-adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases.

Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks

PubMed Central

Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

2018-01-01

Abstract Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic–pituitary–adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases. PMID:29713692

Spectroscopic properties in Er3+-doped germanotellurite glasses and glass ceramics for mid-infrared laser materials.

PubMed

Kang, Shiliang; Xiao, Xiudi; Pan, Qiwen; Chen, Dongdan; Qiu, Jianrong; Dong, Guoping

2017-03-07

Transparent Er 3+ -doped germanotellurite glass ceramics (GCs) with variable Te/Ge ratio were prepared by controllable heat-treated process. X-ray diffraction (XRD) and transmission electron microscope (TEM) confirmed the formation of nanocrystals in glass matrix. Raman spectra were used to investigate the evolution of glass structure and photon energy. Fourier transform infrared (FTIR) spectra were introduced to characterize the change of hydroxyl group (OH - ) content. Enhanced 2.7 μm emission was achieved from Er 3+ -doped GCs upon excitation with a 980 nm laser diode (LD), and the influence of GeO 2 concentration and heat-treated temperature on the spectroscopic properties were also discussed in detail. It is found that the present Er 3+ -doped GC possesses large stimulated emission cross section at around 2.7 μm (0.85 × 10 -20  cm 2 ). The advantageous spectroscopic characteristics suggest that the obtained GC may be a promising material for mid-infrared fiber lasers.

T2N as a new tool for robust electrophysiological modeling demonstrated for mature and adult-born dentate granule cells

PubMed Central

Mongiat, Lucas Alberto; Schwarzacher, Stephan Wolfgang

2017-01-01

Compartmental models are the theoretical tool of choice for understanding single neuron computations. However, many models are incomplete, built ad hoc and require tuning for each novel condition rendering them of limited usability. Here, we present T2N, a powerful interface to control NEURON with Matlab and TREES toolbox, which supports generating models stable over a broad range of reconstructed and synthetic morphologies. We illustrate this for a novel, highly detailed active model of dentate granule cells (GCs) replicating a wide palette of experiments from various labs. By implementing known differences in ion channel composition and morphology, our model reproduces data from mouse or rat, mature or adult-born GCs as well as pharmacological interventions and epileptic conditions. This work sets a new benchmark for detailed compartmental modeling. T2N is suitable for creating robust models useful for large-scale networks that could lead to novel predictions. We discuss possible T2N application in degeneracy studies. PMID:29165247

Spectroscopic properties in Er3+-doped germanotellurite glasses and glass ceramics for mid-infrared laser materials

PubMed Central

Kang, Shiliang; Xiao, Xiudi; Pan, Qiwen; Chen, Dongdan; Qiu, Jianrong; Dong, Guoping

2017-01-01

Transparent Er3+-doped germanotellurite glass ceramics (GCs) with variable Te/Ge ratio were prepared by controllable heat-treated process. X-ray diffraction (XRD) and transmission electron microscope (TEM) confirmed the formation of nanocrystals in glass matrix. Raman spectra were used to investigate the evolution of glass structure and photon energy. Fourier transform infrared (FTIR) spectra were introduced to characterize the change of hydroxyl group (OH−) content. Enhanced 2.7 μm emission was achieved from Er3+-doped GCs upon excitation with a 980 nm laser diode (LD), and the influence of GeO2 concentration and heat-treated temperature on the spectroscopic properties were also discussed in detail. It is found that the present Er3+-doped GC possesses large stimulated emission cross section at around 2.7 μm (0.85 × 10−20 cm2). The advantageous spectroscopic characteristics suggest that the obtained GC may be a promising material for mid-infrared fiber lasers. PMID:28266570

The Use of a Satellite Communications System for Command and Control of the National Aeronautics and Space Administration Surrogate Unmanned Aerial System Research Aircraft

NASA Technical Reports Server (NTRS)

Howell, Charles T.; Jones, Frank; Hutchinson, Brian; Joyce, Claude; Nelson, Skip; Melum, Mike

2017-01-01

The NASA Langley Research Center has transformed a Cirrus Design SR22 general aviation (GA) aircraft into an Unmanned Aerial Systems (UAS) Surrogate research aircraft which has served for several years as a platform for unmanned systems research and development. The aircraft is manned with a Safety Pilot and a Research Systems Operator (RSO) that allows for flight operations almost any-where in the national airspace system (NAS) without the need for a Federal Aviation Administration (FAA) Certificate of Authorization (COA). The UAS Surrogate can be remotely controlled from a modular, transportable ground control station (GCS) like a true UAS. Ground control of the aircraft is accomplished by the use of data links that allow the two-way passage of the required data to control the aircraft and provide the GCS with situational awareness. The original UAS Surrogate data-link system was composed of redundant very high frequency (VHF) data radio modems with a maximum range of approximately 40 nautical miles. A new requirement was developed to extend this range beyond visual range (BVR). This new requirement led to the development of a satellite communications system that provided the means to command and control the UAS Surrogate at ranges beyond the limits of the VHF data links. The system makes use of the Globalstar low earth orbit (LEO) satellite communications system. This paper will provide details of the development, implementation, and flight testing of the satellite data communications system on the UAS Surrogate research aircraft.

The reliability of the Glasgow Coma Scale: a systematic review.

PubMed

Reith, Florence C M; Van den Brande, Ruben; Synnot, Anneliese; Gruen, Russell; Maas, Andrew I R

2016-01-01

The Glasgow Coma Scale (GCS) provides a structured method for assessment of the level of consciousness. Its derived sum score is applied in research and adopted in intensive care unit scoring systems. Controversy exists on the reliability of the GCS. The aim of this systematic review was to summarize evidence on the reliability of the GCS. A literature search was undertaken in MEDLINE, EMBASE and CINAHL. Observational studies that assessed the reliability of the GCS, expressed by a statistical measure, were included. Methodological quality was evaluated with the consensus-based standards for the selection of health measurement instruments checklist and its influence on results considered. Reliability estimates were synthesized narratively. We identified 52 relevant studies that showed significant heterogeneity in the type of reliability estimates used, patients studied, setting and characteristics of observers. Methodological quality was good (n = 7), fair (n = 18) or poor (n = 27). In good quality studies, kappa values were ≥0.6 in 85%, and all intraclass correlation coefficients indicated excellent reliability. Poor quality studies showed lower reliability estimates. Reliability for the GCS components was higher than for the sum score. Factors that may influence reliability include education and training, the level of consciousness and type of stimuli used. Only 13% of studies were of good quality and inconsistency in reported reliability estimates was found. Although the reliability was adequate in good quality studies, further improvement is desirable. From a methodological perspective, the quality of reliability studies needs to be improved. From a clinical perspective, a renewed focus on training/education and standardization of assessment is required.

Glucocorticoids can affect Pseudomonas aeruginosa (ATCC 27853) internalization and intracellular calcium concentration in cystic fibrosis bronchial epithelial cells.

PubMed

Hussain, Rashida; Shahror, Rami; Karpati, Ferenc; Roomans, Godfried M

2015-01-01

Glucocorticoids (GCs) are anti-inflammatory agents, but their use in cystic fibrosis (CF) is controversial. In CF, the early colonization with Pseudomonas aeruginosa is mainly due to nonmucoid strains that can internalize, and induce apoptosis in the epithelial cells. Uptake of P. aeruginosa by the epithelial cells and subsequent apoptosis may prevent colonization of P. aeruginosa in CF airways. In the airway epithelia, several other biological effects, including an anti-secretory role by decreasing intracellular Ca(2+) concentration have been described for this anti-inflammatory drug. However, the effects of GCs on the nonmucoid P. aeruginosa internalization and intracellular Ca(2+) in CF bronchial epithelial cells have not been evaluated. We used cultured human CF bronchial airway epithelial cell (CFBE) monolayers to determine P. aeruginosa internalization, apoptosis, and intracellular Ca(2+)concentration in CF bronchial epithelial cells. Cells were treated with IL-6, IL-8, dexamethasone, betamethasone, or budesonide. GCs in co-treatments with IL-6 reversed the effect of IL-6 by decreasing the internalization of P. aeruginosa in the CFBE cells. GCs decreased the extent of apoptosis in CFBE cells infected with internalized P. aeruginosa, and increased the intracellular Ca(2+) concentration. These findings suggest that if internalization of P. aeruginosa reduces infection, GC therapy would increase the risk of pulmonary infection by decreasing the internalization of P. aeruginosa in CF cells, but GCs may improve airway hydration by increasing the intracellular Ca(2+) concentration. Whether the benefits of GC treatment outweigh the negative effects is questionable, and further clinical studies need to be carried out.

A comparison of "life threatening injury" concept in the Turkish Penal Code and trauma scoring systems.

PubMed

Fedakar, Recep; Aydiner, Ahmet Hüsamettin; Ercan, Ilker

2007-07-01

To compare accuracy and to check the suitability of the Glasgow Coma Scale (GCS), the Revised Trauma Score (RTS), the Injury Severity Score (ISS), the New Injury Severity Score (NISS) and the Trauma and Injury Severity Score (TRISS), the scoring systems widely used in international trauma studies, in the evaluation of the "life threatening injury" concept established by the Turkish Penal Code. The age, sex, type of trauma, type and localizations of wounds, GCS, RTS, ISS, NISS and TRISS values, the decision of life threatening injury of 627 trauma patients admitted to Emergency Department of the Uludag University Medical School Hospital in year 2003 were examined. A life-threatening injury was present in 35.2% of the cases examined. GCS, RTS, ISS, NISS and TRISS confirmed the decision of life threatening injury with percentages of 74.8%, 76.9%, 88.7%, 86.6% and 68.6%, respectively. The best cut-off point 14 was determined in the ISS system with 79.6% sensitivity and 93.6% specificity. All of the cases with sole linear skull fracture officially decided as life threatening injury had an ISS of 5, a NISS of 6 and the best scores of GCS (15), RTS (7.8408) and TRISS (100%). ISS and NISS appeared to be the best trauma scoring systems that can be used for the decision of life threatening injury, compared with GCS, RTS and TRISS. Thus, ISS and NISS can be acceptable for using the evaluation of the life threatening injury concept established by the Turkish Penal Code.

Mortality-Associated Characteristics of Patients with Traumatic Brain Injury at the University Teaching Hospital of Kigali, Rwanda.

PubMed

Krebs, Elizabeth; Gerardo, Charles J; Park, Lawrence P; Nickenig Vissoci, Joao Ricardo; Byiringiro, Jean Claude; Byiringiro, Fidele; Rulisa, Stephen; Thielman, Nathan M; Staton, Catherine A

2017-06-01

Traumatic brain injury (TBI) is a leading cause of death and disability. Patients with TBI in low and middle-income countries have worse outcomes than patients in high-income countries. We evaluated important clinical indicators associated with mortality for patients with TBI at University Teaching Hospital of Kigali, Kigali, Rwanda. A prospective consecutive sampling of patients with TBI presenting to University Teaching Hospital of Kigali Accident and Emergency Department was screened for inclusion criteria: reported head trauma, alteration in consciousness, headache, and visible head trauma. Exclusion criteria were age <10 years, >48 hours after injury, and repeat visit. Data were assessed for association with death using logistic regression. Significant variables were included in a multivariate logistic regression model and refined via backward elimination. Between October 7, 2013, and April 6, 2014, 684 patients were enrolled; 14 (2%) were excluded because of incomplete data. Of patients, 81% were male with mean age of 31 years (range, 10-89 years; SD 11.8). Most patients (80%) had mild TBI (Glasgow Coma Scale [GCS] score 13-15); 10% had moderate (GCS score 9-12) and 10% had severe (GCS score 3-8) TBI. Multivariate logistic regression determined that GCS score <13, hypoxia, bradycardia, tachycardia, and age >50 years were significantly associated with death. GCS score <13, hypoxia, bradycardia, tachycardia, and age >50 years were associated with mortality. These findings inform future research that may guide clinicians in prioritizing care for patients at highest risk of mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

Prohibitin (PHB) acts as a potent survival factor against ceramide induced apoptosis in rat granulosa cells.

PubMed

Chowdhury, Indrajit; Branch, Alicia; Olatinwo, Moshood; Thomas, Kelwyn; Matthews, Roland; Thompson, Winston E

2011-08-29

Ceramide is a key factor in inducing germ cell apoptosis by translocating from cumulus cells into the adjacent oocyte and lipid rafts through gap junctions. Therefore studies designed to elucidate the mechanistic pathways in ceramide induced granulosa cell (GC) apoptosis and follicular atresia may potentially lead to the development of novel lipid-based therapeutic strategies that will prevent infertility and premature menopause associated with chemo and/or radiation therapy in female cancer patients. Our previous studies have shown that Prohibitin (PHB) is intimately involved in GCs differentiation, atresia, and luteolysis. In the present study, we have examined the functional effects of loss-/gain-of-function of PHB using adenoviral technology in delaying apoptosis induced by the physiological ligand ceramide in rat GCs. Under these experimental conditions, exogenous ceramide C-8 (50 μM) augmented the expression of mitochondrial PHB and subsequently cause the physical destruction of GC by the release of mitochondrial cytochrome c and activation of caspase-3. In further studies, silencing of PHB expression by adenoviral small interfering RNA (shRNA) sensitized GCs to ceramide C8-induce apoptosis. In contrast, adenovirus (Ad) directed overexpression of PHB in GCs resulted in increased PHB content in mitochondria and delayed the onset of ceramide induced apoptosis in the infected GCs. Taken together, these results provide novel evidences that a critical level of PHB expression within the mitochondria plays a key intra-molecular role in GC fate by mediating the inhibition of apoptosis and may therefore, contribute significantly to ceramide induced follicular atresia. Copyright © 2011 Elsevier Inc. All rights reserved.

COOP+ project: Promoting the cooperation of international Research Infrastructures to address global environmental challenges.

NASA Astrophysics Data System (ADS)

Bonet-García, F.; Järvi, L.; Asmi, A.; Suárez-Muñoz, M.

2016-12-01

Humanity must face enormous environmental challenges including biodiversity decline, climate change, ocean acidification, sea level rise and overpopulation. The research infrastructures (RIs) created in the last decades worldwide cover a wide range of spatial and thematic scales and collect information about the functioning of Earth ecosystems. However, we need to go one step forward: understand and simulate the functioning of the Earth as a complex system in a global change scenario. Cooperation among international RIs as well as multidisciplinary work are mandatory to achieve this challenging objective. COOP+ (EU Horizon 2020 project) aims to strengthen the links and coordination of European environmental RIs with their international counterparts. COOP+ will create cooperation threads among international research infrastructures using environmental Global Challenges (GCs) as thematic guidelines. These GCs are polyhedral and sometimes wicked problems that threaten the sustainability of our modern societies from a social and environmental perspective. This contribution describes how COOP+ uses GCs as guidelines to foster cooperation among RIs. First we have created an open survey to collect ideas about GCs within the different scientific communities. We present the structure of this survey as well as the preliminary information that it contains. The survey will be accepting responses during the project life (September 2018). We also describe the structure of a template that will be used to collaboratively characterize some selected GCs under the point of view of RIs. The main idea is to assess how RIs can be useful to address global environmental problems. We encourage all scientists related to RIs communities to participate in this process.

Factors Influencing the Reliability of the Glasgow Coma Scale: A Systematic Review.

PubMed

Reith, Florence Cm; Synnot, Anneliese; van den Brande, Ruben; Gruen, Russell L; Maas, Andrew Ir

2017-06-01

The Glasgow Coma Scale (GCS) characterizes patients with diminished consciousness. In a recent systematic review, we found overall adequate reliability across different clinical settings, but reliability estimates varied considerably between studies, and methodological quality of studies was overall poor. Identifying and understanding factors that can affect its reliability is important, in order to promote high standards for clinical use of the GCS. The aim of this systematic review was to identify factors that influence reliability and to provide an evidence base for promoting consistent and reliable application of the GCS. A comprehensive literature search was undertaken in MEDLINE, EMBASE, and CINAHL from 1974 to July 2016. Studies assessing the reliability of the GCS in adults or describing any factor that influences reliability were included. Two reviewers independently screened citations, selected full texts, and undertook data extraction and critical appraisal. Methodological quality of studies was evaluated with the consensus-based standards for the selection of health measurement instruments checklist. Data were synthesized narratively and presented in tables. Forty-one studies were included for analysis. Factors identified that may influence reliability are education and training, the level of consciousness, and type of stimuli used. Conflicting results were found for experience of the observer, the pathology causing the reduced consciousness, and intubation/sedation. No clear influence was found for the professional background of observers. Reliability of the GCS is influenced by multiple factors and as such is context dependent. This review points to the potential for improvement from training and education and standardization of assessment methods, for which recommendations are presented. Copyright © 2017 by the Congress of Neurological Surgeons.

Clear Evidence for the Presence of Second-generation Asymptotic Giant Branch Stars in Metal-poor Galactic Globular Clusters

NASA Astrophysics Data System (ADS)

García-Hernández, D. A.; Mészáros, Sz.; Monelli, M.; Cassisi, S.; Stetson, P. B.; Zamora, O.; Shetrone, M.; Lucatello, S.

2015-12-01

Galactic globular clusters (GCs) are known to host multiple stellar populations: a first generation (FG) with a chemical pattern typical of halo field stars and a second generation (SG) enriched in Na and Al and depleted in O and Mg. Both stellar generations are found at different evolutionary stages (e.g., the main-sequence turnoff, the subgiant branch, and the red giant branch (RGB)). The non detection of SG asymptotic giant branch (AGB) stars in several metal-poor ([Fe/H] < -1) GCs suggests that not all SG stars ascend the AGB phase, and that failed AGB stars may be very common in metal-poor GCs. This observation represents a serious problem for stellar evolution and GC formation/evolution theories. We report fourteen SG-AGB stars in four metal-poor GCs (M13, M5, M3, and M2) with different observational properties: horizontal branch (HB) morphology, metallicity, and age. By combining the H-band Al abundances obtained by the Apache Point Observatory Galactic Evolution Experiment survey with ground-based optical photometry, we identify SG Al-rich AGB stars in these four GCs and show that Al-rich RGB/AGB GC stars should be Na-rich. Our observations provide strong support for present, standard stellar models, i.e., without including a strong mass-loss efficiency, for low-mass HB stars. In fact, current empirical evidence is in agreement with the predicted distribution of FG and SG stars during the He-burning stages based on these standard stellar models.

Accuracy in identifying patients with loss of consciousness in a police-operated emergency call centre - first step in the chain of survival.

PubMed

Bach, A; Christensen, E F

2007-07-01

The first link in the 'chain of survival' is the activation of Emergency Medical Services (EMS). In the major part of Denmark, police officers operate the alarm 1-1-2 centre, including calls for EMS. Our aim was to study the police 1-1-2 operators' accuracy in identifying calls concerning patients with loss of consciousness as a key symptom of life-threatening conditions. 'Unconsciousness' was defined as patients with a Glasgow Coma Scale (GCS) score of < 9, scored by the on-scene anaesthesiologist from the Mobile Emergency Care Unit (MECU). This study was an observational cohort study based on data from the Police 1-1-2 Database and the Aarhus County Pre-hospital Database containing data from MECU cases during 6 months in 2004-05. Two thousand, three hundred and forty-three emergency calls with MECU dispatch were identified. In 1655 cases, both 1-1-2 data and the GCS score were recorded. Two hundred and ninety-five patients were found with a GCS score of < 9 at MECU arrival, 243 of whom were reported 'unconscious' by 1-1-2, giving a sensitivity of 82%. One thousand, three hundred and sixty patients were found with a GCS score of > or = 9, 972 of whom were reported 'awake', giving a specificity of 72%. The positive predictive value (percentage of patients found with a GCS score of < 9 at MECU arrival amongst patients reported as 'unconscious') was 39%. The accuracy was moderate with room for improvement. The positive predictive value was low, indicating over-triage of MECU.

An audit of traumatic brain injury (TBI) in a busy developing-world trauma service exposes a significant deficit in resources available to manage severe TBI.

PubMed

Jerome, Ellen; Laing, Grant L; Bruce, John L; Sartorius, Ben; Brysiewicz, Petra; Clarke, Damian L

2017-06-30

Traumatic brain injury (TBI) affects large numbers of patients, both adults and children, and significant resources are needed to manage it. To determine the burden of TBI and the adequacy of available resources to manage in the Pietermaritzburg Metropolitan Trauma Service (PMTS). All patients with a TBI were identified from the hybrid electronic medical registry at Grey's and Edendale hospitals in Pietermaritzburg (PMB), KwaZulu-Natal, South Africa. Patients were classified according to severity of head injury and age. We defined mild TBI as Glasgow coma scale (GCS) 13 - 15, moderate as GCS 9 - 12, and severe as GCS ≤8, in accordance with international standards. We divided the cohort according to ages 0 - 5 years, 6 - 10 years, >10 - 17 years and adults (>17 years). From January 2012 to December 2014, 3 301 patients were treated for TBI in PMB. The mean age was 27.4 (standard deviation 14.4) years. There were 2 632 males and 564 females. There were 2 540 mild, 326 moderate, and 329 severe TBI admissions during the period under review. A total of 139 (4.2%) patients died. A total of 242 (7.3%) patients were admitted to the intensive care unit (ICU), of whom 137 (57.0%) had a GCS of ≤9. Only 27.0% of patients with a GCS of ≤9 were admitted to the ICU. There is a significant burden of TBI managed by the PMTS. Critical care resources available to manage patients with TBI are inadequate.

Somatic frameshift mutations in the Bloom syndrome BLM gene are frequent in sporadic gastric carcinomas with microsatellite mutator phenotype

PubMed Central

Calin, George; Ranzani, Guglielmina N; Amadori, Dino; Herlea, Vlad; Matei, Irina; Barbanti-Brodano, Giuseppe; Negrini, Massimo

2001-01-01

Background Genomic instability has been reported at microsatellite tracts in few coding sequences. We have shown that the Bloom syndrome BLM gene may be a target of microsatelliteinstability (MSI) in a short poly-adenine repeat located in its coding region. To further characterize the involvement of BLM in tumorigenesis, we have investigated mutations in nine genes containing coding microsatellites in microsatellite mutator phenotype (MMP) positive and negative gastric carcinomas (GCs). Methods We analyzed 50 gastric carcinomas (GCs) for mutations in the BLM poly(A) tract aswell as in the coding microsatellites of the TGFβ1-RII, IGFIIR, hMSH3, hMSH6, BAX, WRN, RECQL and CBL genes. Results BLM mutations were found in 27% of MMP+ GCs (4/15 cases) but not in any of the MMP negative GCs (0/35 cases). The frequency of mutations in the other eight coding regions microsatellite was the following: TGFβ1-RII (60 %), BAX (27%), hMSH6 (20%),hMSH3 (13%), CBL (13%), IGFIIR (7%), RECQL (0%) and WRN (0%). Mutations in BLM appear to be more frequently associated with frameshifts in BAX and in hMSH6and/or hMSH3. Tumors with BLM alterations present a higher frequency of unstable mono- and trinucleotide repeats located in coding regions as compared with mutator phenotype tumors without BLM frameshifts. Conclusions BLM frameshifts are frequent alterations in GCs specifically associated with MMP+tumors. We suggest that BLM loss of function by MSI may increase the genetic instability of a pre-existent unstable genotype in gastric tumors. PMID:11532193

Characterization of Unconventional Reservoirs: CO2 Induced Petrophysics

NASA Astrophysics Data System (ADS)

Verba, C.; Goral, J.; Washburn, A.; Crandall, D.; Moore, J.

2017-12-01

As concerns about human-driven CO2 emissions grow, it is critical to develop economically and environmentally effective strategies to mitigate impacts associated with fossil energy. Geologic carbon storage (GCS) is a potentially promising technique which involves the injection of captured CO2 into subsurface formations. Unconventional shale formations are attractive targets for GCS while concurrently improving gas recovery. However, shales are inherently heterogeneous, and minor differences can impact the ability of the shale to effectively adsorb and store CO2. Understanding GCS capacity from such endemic heterogeneities is further complicated by the complex geochemical processes which can dynamically alter shale petrophysics. We investigated the size distribution, connectivity, and type (intraparticle, interparticle, and organic) of pores in shale; the mineralogy of cores from unconventional shale (e.g. Bakken); and the changes to these properties under simulated GCS conditions. Electron microscopy and dual beam focused ion beam scanning electron microscopy were used to reconstruct 2D/3D digital matrix and pore structures. Comparison of pre and post-reacted samples gives insights into CO2-shale interactions - such as the mechanism of CO2 sorption in shales- intended for enhanced oil recovery and GCS initiatives. These comparisons also show how geochemical processes proceed differently across shales based on their initial diagenesis. Results show that most shale pore sizes fall within meso-macro pore classification (> 2 nm), but have variable porosity and organic content. The formation of secondary minerals (calcite, gypsum, and halite) may play a role in the infilling of fractures and pore spaces in the shale, which may reduce permeability and inhibit the flow of fluids.

Power, Discourse, and Learning Global Citizenship: A Case Study of International NGOs and a Grassroots Movement in the Narmada Valley, India

ERIC Educational Resources Information Center

Shukla, Natasha

2009-01-01

The field of transnational contestation conceptualized as global civil society (GCS) is gaining academic interest as a political "counter-force" against the exigencies of globalization. However, social actors within GCS occupy unequal positions of power in relation to each other. This article examines how the discourses of transnational action…

Electrical behavior of aluminosilicate glass-ceramic sealants and their interaction with metallic solid oxide fuel cell interconnects

NASA Astrophysics Data System (ADS)

Goel, Ashutosh; Tulyaganov, Dilshat U.; Kharton, Vladislav V.; Yaremchenko, Aleksey A.; Ferreira, José M. F.

A series of alkaline-earth aluminosilicate glass-ceramics (GCs) were appraised with respect to their suitability as sealants for solid oxide fuel cells (SOFCs). The parent composition with general formula Ca 0.9MgAl 0.1La 0.1Si 1.9O 6 was modified with Cr 2O 3 and BaO. The addition of BaO led to a substantial decrease in the total electrical conductivity of the GCs, thus improving their insulating properties. BaO-containing GCs exhibited higher coefficient of thermal expansion (CTE) in comparison to BaO-free GCs. An extensive segregation of oxides of Ti and Mn, components of the Crofer22 APU interconnect alloy, along with negligible formation of BaCrO 4 was observed at the interface between GC/interconnects diffusion couples. Thermal shock resistance and gas-tightness of GC sealants in contact with yttria-stabilized zirconia electrolyte (8YSZ) was evaluated in air and water. Good matching of CTE and strong, but not reactive, adhesion to the solid electrolyte and interconnect, in conjunction with a high level of electrical resistivity, are all advantageous for potential SOFC applications.

Effect of Corticosteroids on Pain Relief Following Root Canal Treatment: A Systematic Review.

PubMed

Iranmanesh, Foad; Parirokh, Masoud; Haghdoost, Ali Akbar; Abbott, Paul V

2017-01-01

Post-operative pain and flare-up may occur in up to 58% of patients following root canal treatment. The aim was to conduct a systematic review and a possible meta-analysis to determine the effect of glucocorticosteroid (GCS) on pain following root canal treatment. Scopus, MEDLINE and CENTRAL databases were searched up to 30 th January 2017 with broad key words. In addition, the reference lists in eligible papers and text books were hand-searched. Assessment of the eligibility of papers and data extraction were performed by two independent reviewers. Of 9891 articles, 18 were recruited as eligible papers. Most of these papers showed pain reducing effect of GCS on post-endodontic pain. Because of wide heterogeneity among the recruited papers, it was not possible to perform meta-analysis. Based on the results of this systematic review, there is a vast heterogeneity amongst articles regarding the use of GCS and their effect on post-operative pain after endodontic treatment. Further investigations with similar methods and materials are needed before meta-analysis on the effect of GCS on post-operative pain following root canal treatment can be performed .

HDAC2 is required by the physiological concentration of glucocorticoid to inhibit inflammation in cardiac fibroblasts.

PubMed

Zhang, Haining; He, Yanhua; Zhang, Guiping; Li, Xiaobin; Yan, Suikai; Hou, Ning; Xiao, Qing; Huang, Yue; Luo, Miaoshan; Zhang, Genshui; Yi, Quan; Chen, Minsheng; Luo, Jiandong

2017-09-01

We previously suggested that endogenous glucocorticoids (GCs) may inhibit myocardial inflammation induced by lipopolysaccharide (LPS) in vivo. However, the possible cellular and molecular mechanisms were poorly understood. In this study, we investigated the role of physiological concentration of GCs in inflammation induced by LPS in cardiac fibroblasts and explored the possible mechanisms. The results showed that hydrocortisone at the dose of 127 ng/mL (equivalent to endogenous basal level of GCs) inhibited LPS (100 ng/mL)-induced productions of TNF-α and IL-1β in cardiac fibroblasts. Xanthine oxidase/xanthine (XO/X) system impaired the anti-inflammatory action of GCs through downregulating HDAC2 activity and expression. Knockdown of HDAC2 restrained the anti-inflammatory effects of physiological level of hydrocortisone, and blunted the ability of XO/X system to downregulate the inhibitory action of physiological level of hydrocortisone on cytokines. These results suggested that HDAC2 was required by the physiological concentration of GC to inhibit inflammatory response. The dysfunction of HDAC2 induced by oxidative stress might be account for GC resistance and chronic inflammatory disorders during the cardiac diseases.

Development of a Streamlined Work Flow for Handling Patients' Genetic Testing Insurance Authorizations.

PubMed

Uhlmann, Wendy R; Schwalm, Katie; Raymond, Victoria M

2017-08-01

Obtaining genetic testing insurance authorizations for patients is a complex, time-involved process often requiring genetic counselor (GC) and physician involvement. In an effort to mitigate this complexity and meet the increasing number of genetic testing insurance authorization requests, GCs formed a novel partnership with an industrial engineer (IE) and a patient services associate (PSA) to develop a streamlined work flow. Eight genetics clinics and five specialty clinics at the University of Michigan were surveyed to obtain benchmarking data. Tasks needed for genetic testing insurance authorization were outlined and time-saving work flow changes were introduced including 1) creation of an Excel password-protected shared database between GCs and PSAs, used for initiating insurance authorization requests, tracking and follow-up 2) instituting the PSAs sending GCs a pre-clinic email noting each patients' genetic testing insurance coverage 3) inclusion of test medical necessity documentation in the clinic visit summary note instead of writing a separate insurance letter and 4) PSAs development of a manual with insurance providers and genetic testing laboratories information. These work flow changes made it more efficient to request and track genetic testing insurance authorizations for patients, enhanced GCs and PSAs communication, and reduced tasks done by clinicians.

Histone deacetylase inhibitor stimulates E2 and P4 secretion in sika deer ovarian granulosa cells at a moderate dose.

PubMed

Xing, Mingjie; Chen, Xiumin; Li, Xiaoxia; Yang, Yifeng; Wang, Xiaoxu; Cao, Xinyan; Xue, Hailong; Wang, Shiyong; Diao, Yunfei; Zhao, Weigang; Zhao, Meng; Cui, Xuezhe; Chang, Tong; Xu, Baozeng; Wei, Haijun

2018-03-01

The histone deacetylase inhibitor (HDACi) and tumor suppressor play an important role in genome reorganization and epigenetic regulation. In this study, granulosa cells (GCs) isolated from sika deer ovaries were cultured and treated with different concentrations of trichostatin A (TSA) for 48 h. It was found that TSA inhibited GCs proliferation and induced GCs apoptosis by upregulating expression of BAX, meanwhile, downregulating expression of GLUT3, GLUT8, BCL-XL. In addition, TSA caused cell cycle arrest at the G1 and G2/M phase accompanied by reducing expression of Cyclin D2 and CDK4. TSA pretreatment increased DNMT3a, DNMT1, HDAC1, and HAT1 expression, and attenuated them when TAS higher than 50 nM. The protein levels of H3K9ac and H4K8ac in GCs were increased at 48 h after TSA treatment. TSA stimulated the secretion of estradiol and progesterone at a moderate dose. Our data suggest that TSA is important as a regulator of steroid hormone synthesis in granulosa cells during follicular development in the sika deer ovary. © 2018 International Federation for Cell Biology.

Dexamethasone alters the expression of genes related to the growth of skeletal muscle in chickens (Gallus gallus domesticus).

PubMed

Song, Z G; Zhang, X H; Zhu, L X; Jiao, H C; Lin, H

2011-06-01

Glucocorticoids (GCs) are involved in the muscle wasting caused by trauma, inactivity, and stress. In the present study, three experiments were conducted to investigate the effect of GCs on the expression of genes related to muscle development in chickens. Broilers at 7 or 35 days of age were subjected to dexamethasone (DEX) treatment (2 mg/kg body mass (BM)) for 3 or 7 days. The expression levels of genes such as IGF1, IGF1 receptor, MSTN, WW domain containing E3 ubiquitin (UB) protein ligase 1, myogenic determining factor, and myogenic factor 5 were measured. The results showed that BM gain was significantly suppressed by DEX treatment. The plasma level of insulin was increased (P<0.05) by DEX treatment at feeding, whereas IGF1 was decreased (P<0.05). The expression of genes in the IGF1, myostatin, and UB-proteasome (UBP) pathways were altered by DEX treatment in age- and exposure time-related ways. These results suggest that GCs suppress IGF1 and upregulate myostatin and/or activated myostatin and the UBP pathway, which might be the source of the effect of GCs on muscle development.

Input integration around the dendritic branches in hippocampal dentate granule cells.

PubMed

Kamijo, Tadanobu Chuyo; Hayakawa, Hirofumi; Fukushima, Yasuhiro; Kubota, Yoshiyuki; Isomura, Yoshikazu; Tsukada, Minoru; Aihara, Takeshi

2014-08-01

Recent studies have shown that the dendrites of several neurons are not simple translators but are crucial facilitators of excitatory postsynaptic potential (EPSP) propagation and summation of synaptic inputs to compensate for inherent voltage attenuation. Granule cells (GCs)are located at the gateway for valuable information arriving at the hippocampus from the entorhinal cortex. However, the underlying mechanisms of information integration along the dendrites of GCs in the hippocampus are still unclear. In this study, we investigated the input integration around dendritic branches of GCs in the rat hippocampus. We applied differential spatiotemporal stimulations to the dendrites using a high-speed glutamate-uncaging laser. Our results showed that when two sites close to and equidistant from a branching point were simultaneously stimulated, a nonlinear summation of EPSPs was observed at the soma. In addition, nonlinear summation (facilitation) depended on the stimulus location and was significantly blocked by the application of a voltage-dependent Ca(2+) channel antagonist. These findings suggest that the nonlinear summation of EPSPs around the dendritic branches of hippocampal GCs is a result of voltage-dependent Ca(2+) channel activation and may play a crucial role in the integration of input information.

A view of the H-band light-element chemical patterns in globular clusters under the AGB self-enrichment scenario

NASA Astrophysics Data System (ADS)

Dell'Agli, F.; García-Hernández, D. A.; Ventura, P.; Mészáros, Sz; Masseron, T.; Fernández-Trincado, J. G.; Tang, B.; Shetrone, M.; Zamora, O.; Lucatello, S.

2018-04-01

We discuss the self-enrichment scenario by asymptotic giant branch (AGB) stars for the formation of multiple populations in globular clusters (GCs) by analysing data set of giant stars observed in nine Galactic GCs, covering a wide range of metallicities and for which the simultaneous measurements of C, N, O, Mg, Al, and Si are available. To this aim, we calculated six sets of AGB models, with the same chemical composition as the stars belonging to the first generation of each GC. We find that the AGB yields can reproduce the set of observations available, not only in terms of the degree of contamination shown by stars in each GC but, more important, also the observed trend with metallicity, which agrees well with the predictions from AGB evolution modelling. While further observational evidences are required to definitively fix the main actors in the pollution of the interstellar medium from which new generation of stars formed in GCs, the present results confirm that the gas ejected by stars of mass in the range 4 M_{⊙} ≤ M ≤ 8 M_{⊙} during the AGB phase share the same chemical patterns traced by stars in GCs.

The Metal-poor non-Sagittarius (?) Globular Cluster NGC 5053: Orbit and Mg, Al, and Si Abundances

NASA Astrophysics Data System (ADS)

Tang, Baitian; Fernández-Trincado, J. G.; Geisler, Doug; Zamora, Olga; Mészáros, Szabolcs; Masseron, Thomas; Cohen, Roger E.; García-Hernández, D. A.; Dell’Agli, Flavia; Beers, Timothy C.; Schiavon, Ricardo P.; Sohn, Sangmo Tony; Hasselquist, Sten; Robin, Annie C.; Shetrone, Matthew; Majewski, Steven R.; Villanova, Sandro; Schiappacasse Ulloa, Jose; Lane, Richard R.; Minnti, Dante; Roman-Lopes, Alexandre; Almeida, Andres; Moreno, E.

2018-03-01

Metal-poor globular clusters (GCs) exhibit intriguing Al–Mg anti-correlations and possible Si–Al correlations, which are important clues to decipher the multiple-population phenomenon. NGC 5053 is one of the most metal-poor GCs in the nearby universe and has been suggested to be associated with the Sagittarius (Sgr) dwarf galaxy, due to its similarity in location and radial velocity with one of the Sgr arms. In this work, we simulate the orbit of NGC 5053, and argue against a physical connection between Sgr and NGC 5053. On the other hand, the Mg, Al, and Si spectral lines, which are difficult to detect in the optical spectra of NGC 5053 stars, have been detected in the near-infrared APOGEE spectra. We use three different sets of stellar parameters and codes to derive the Mg, Al, and Si abundances. Regardless of which method is adopted, we see a large Al variation, and a substantial Si spread. Along with NGC 5053, metal-poor GCs exhibit different Mg, Al, and Si variations. Moreover, NGC 5053 has the lowest cluster mass among the GCs that have been identified to exhibit an observable Si spread until now.

Higher glucocorticoid secretion in the physiological range is associated with lower bone strength at the proximal radius in healthy children: importance of protein intake adjustment.

PubMed

Shi, Lijie; Sánchez-Guijo, Alberto; Hartmann, Michaela F; Schönau, Eckhard; Esche, Jonas; Wudy, Stefan A; Remer, Thomas

2015-02-01

Whether higher production of glucocorticoids (GCs) within the physiological range may already be affecting bone status in healthy children is unknown. Because dietary protein intake affects both bone and GCs, we examined the association of urinary measures of glucocorticoid status and cortical bone in healthy non-obese children, after particularly controlling for protein intake. Proximal forearm bone parameters were measured by peripheral quantitative computed tomography (pQCT). Subjects studied (n = 175, 87 males, aged 6 to 18 years) had two 24-hour urine samples collected: the first sample at 1 year before bone measurement, and the second sample at the time of bone measurement. Major urinary GC metabolites were measured by mass spectrometry and summed to assess daily adrenal GC secretion (∑C21). Urinary free cortisol (UFF) and cortisone (UFE) were summed to assess potentially bioactive free GCs (UFF + UFE). After controlling for several covariates and especially urinary nitrogen (the biomarker of protein intake) cortisol secretion ∑C21 was inversely associated with all analyzed pQCT measures of bone quality. ∑C21 also predicted a higher endosteal and lower periosteal circumference, explaining both a smaller cortical area and (together with lower BMD) a lower strength-strain-index (SSI). UFF + UFE, UFE itself, and a urinary metabolite-estimate of 11beta-hydroxysteroid dehydrogenase type1 (11beta-HSD1) activity showed corresponding reciprocal associations (p < 0.05) with BMD and bone mineral content, but not with SSI and bone geometry variables. In conclusion, higher GC levels, even within the physiological range, appear to exert negative influences on bone modeling and remodeling already during growth. Our physiological data also suggest a relevant role of cortisone as the direct source for intracrine-generated cortisol by bone cell 11beta-HSD1. © 2014 American Society for Bone and Mineral Research.

Instrument Display Visual Angles for Conventional Aircraft and the MQ-9 Ground Control Station

NASA Technical Reports Server (NTRS)

Kamine, Tovy Haber; Bendrick, Gregg A.

2008-01-01

Aircraft instrument panels should be designed such that primary displays are in optimal viewing location to minimize pilot perception and response time. Human Factors engineers define three zones (i.e. cones ) of visual location: 1) "Easy Eye Movement" (foveal vision); 2) "Maximum Eye Movement" (peripheral vision with saccades), and 3) "Head Movement (head movement required). Instrument display visual angles were measured to determine how well conventional aircraft (T-34, T-38, F- 15B, F-16XL, F/A-18A, U-2D, ER-2, King Air, G-III, B-52H, DC-10, B747-SCA) and the MQ-9 ground control station (GCS) complied with these standards, and how they compared with each other. Selected instrument parameters included: attitude, pitch, bank, power, airspeed, altitude, vertical speed, heading, turn rate, slip/skid, AOA, flight path, latitude, longitude, course, bearing, range and time. Vertical and horizontal visual angles for each component were measured from the pilot s eye position in each system. The vertical visual angles of displays in conventional aircraft lay within the cone of "Easy Eye Movement" for all but three of the parameters measured, and almost all of the horizontal visual angles fell within this range. All conventional vertical and horizontal visual angles lay within the cone of Maximum Eye Movement. However, most instrument vertical visual angles of the MQ-9 GCS lay outside the cone of Easy Eye Movement, though all were within the cone of Maximum Eye Movement. All the horizontal visual angles for the MQ-9 GCS were within the cone of "Easy Eye Movement". Most instrument displays in conventional aircraft lay within the cone of Easy Eye Movement, though mission-critical instruments sometimes displaced less important instruments outside this area. Many of the MQ-9 GCS systems lay outside this area. Specific training for MQ-9 pilots may be needed to avoid increased response time and potential error during flight. The learning objectives include: 1) Know three physiologic cones of eye/head movement; 2) Understand how instrument displays comply with these design principles in conventional aircraft and an uninhabited aerial vehicle system. Which of the following is NOT a recognized physiologic principle of instrument display design? Cone of Easy Eye Movement 2) Cone of Binocular Eye Movement 3) Cone of Maximum Eye Movement 4) Cone of Head Movement 5) None of the above. Answer: # 2) Cone of Binocular Eye Movement

Modulation of gonadotrophin induced steroidogenic enzymes in granulosa cells by d-chiroinositol.

PubMed

Sacchi, Sandro; Marinaro, Federica; Tondelli, Debora; Lui, Jessica; Xella, Susanna; Marsella, Tiziana; Tagliasacchi, Daniela; Argento, Cindy; Tirelli, Alessandra; Giulini, Simone; La Marca, Antonio

2016-08-31

d-chiroinositol (DCI) is a inositolphosphoglycan (IPG) involved in several cellular functions that control the glucose metabolism. DCI functions as second messenger in the insulin signaling pathway and it is considered an insulin sensitizer since deficiency in tissue availability of DCI were shown to cause insulin resistance (IR). Polycystic ovary syndrome (PCOS) is a pathological condition that is often accompanied with insulin resistance. DCI can positively affects several aspect of PCOS etiology decreasing the total and free testosterone, lowering blood pressure, improving the glucose metabolism and increasing the ovulation frequency. The purpose of this study was to evaluate the effects of DCI and insulin combined with gonadotrophins namely follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on key steroidogenic enzymes genes regulation, cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and cytochrome P450 side-chain cleavage (P450scc) in primary cultures of human granulosa cells (hGCs). We also investigated whether DCI, being an insulin-sensitizer would be able to counteract the expected stimulator activity of insulin on human granulosa cells (hGCs). The study was conducted on primary cultures of hGCs. Gene expression was evaluated by RT-qPCR method. Statistical analysis was performed applying student t-test, as appropriate (P < 0.05) set for statistical significance. DCI is able to reduce the gene expression of CYP19A1, P450scc and insulin-like growth factor 1 receptor (IGF-1R) in dose-response manner. The presence of DCI impaired the increased expression of steroidogenic enzyme genes generated by the insulin treatment in gonadotrophin-stimulated hGCs. Insulin acts as co-gonadotrophin increasing the expression of steroidogenic enzymes genes in gonadotrophin-stimulated granulosa cells. DCI is an insulin-sensitizer that counteracts this action by reducing the expression of the genes CYP19A1, P450scc and IGF-1R. The ability of DCI to modulate in vitro ovarian activity of insulin could in part explain its beneficial effect when used as treatment for conditions associated to insulin resistance.

Disruption of centrifugal inhibition to olfactory bulb granule cells impairs olfactory discrimination.

PubMed

Nunez-Parra, Alexia; Maurer, Robert K; Krahe, Krista; Smith, Richard S; Araneda, Ricardo C

2013-09-03

Granule cells (GCs) are the most abundant inhibitory neuronal type in the olfactory bulb and play a critical role in olfactory processing. GCs regulate the activity of principal neurons, the mitral cells, through dendrodendritic synapses, shaping the olfactory bulb output to other brain regions. GC excitability is regulated precisely by intrinsic and extrinsic inputs, and this regulation is fundamental for odor discrimination. Here, we used channelrhodopsin to stimulate GABAergic axons from the basal forebrain selectively and show that this stimulation generates reliable inhibitory responses in GCs. Furthermore, selective in vivo inhibition of GABAergic neurons in the basal forebrain by targeted expression of designer receptors exclusively activated by designer drugs produced a reversible impairment in the discrimination of structurally similar odors, indicating an important role of these inhibitory afferents in olfactory processing.

LISA Sources in Milky Way Globular Clusters

NASA Astrophysics Data System (ADS)

Kremer, Kyle; Chatterjee, Sourav; Breivik, Katelyn; Rodriguez, Carl L.; Larson, Shane L.; Rasio, Frederic A.

2018-05-01

We explore the formation of double-compact-object binaries in Milky Way (MW) globular clusters (GCs) that may be detectable by the Laser Interferometer Space Antenna (LISA). We use a set of 137 fully evolved GC models that, overall, effectively match the properties of the observed GCs in the MW. We estimate that, in total, the MW GCs contain ˜21 sources that will be detectable by LISA. These detectable sources contain all combinations of black hole (BH), neutron star, and white dwarf components. We predict ˜7 of these sources will be BH-BH binaries. Furthermore, we show that some of these BH-BH binaries can have signal-to-noise ratios large enough to be detectable at the distance of the Andromeda galaxy or even the Virgo cluster.

LISA Sources in Milky Way Globular Clusters.

PubMed

Kremer, Kyle; Chatterjee, Sourav; Breivik, Katelyn; Rodriguez, Carl L; Larson, Shane L; Rasio, Frederic A

2018-05-11

We explore the formation of double-compact-object binaries in Milky Way (MW) globular clusters (GCs) that may be detectable by the Laser Interferometer Space Antenna (LISA). We use a set of 137 fully evolved GC models that, overall, effectively match the properties of the observed GCs in the MW. We estimate that, in total, the MW GCs contain ∼21 sources that will be detectable by LISA. These detectable sources contain all combinations of black hole (BH), neutron star, and white dwarf components. We predict ∼7 of these sources will be BH-BH binaries. Furthermore, we show that some of these BH-BH binaries can have signal-to-noise ratios large enough to be detectable at the distance of the Andromeda galaxy or even the Virgo cluster.

Drosophila growth cones: a genetically tractable platform for the analysis of axonal growth dynamics.

PubMed

Sánchez-Soriano, Natalia; Gonçalves-Pimentel, Catarina; Beaven, Robin; Haessler, Ulrike; Ofner-Ziegenfuss, Lisa; Ballestrem, Christoph; Prokop, Andreas

2010-01-01

The formation of neuronal networks, during development and regeneration, requires outgrowth of axons along reproducible paths toward their appropriate postsynaptic target cells. Axonal extension occurs at growth cones (GCs) at the tips of axons. GC advance and navigation requires the activity of their cytoskeletal networks, comprising filamentous actin (F-actin) in lamellipodia and filopodia as well as dynamic microtubules (MTs) emanating from bundles of the axonal core. The molecular mechanisms governing these two cytoskeletal networks, their cross-talk, and their response to extracellular signaling cues are only partially understood, hindering our conceptual understanding of how regulated changes in GC behavior are controlled. Here, we introduce Drosophila GCs as a suitable model to address these mechanisms. Morphological and cytoskeletal readouts of Drosophila GCs are similar to those of other models, including mammals, as demonstrated here for MT and F-actin dynamics, axonal growth rates, filopodial structure and motility, organizational principles of MT networks, and subcellular marker localization. Therefore, we expect fundamental insights gained in Drosophila to be translatable into vertebrate biology. The advantage of the Drosophila model over others is its enormous amenability to combinatorial genetics as a powerful strategy to address the complexity of regulatory networks governing axonal growth. Thus, using pharmacological and genetic manipulations, we demonstrate a role of the actin cytoskeleton in a specific form of MT organization (loop formation), known to regulate GC pausing behavior. We demonstrate these events to be mediated by the actin-MT linking factor Short stop, thus identifying an essential molecular player in this context.

Balancing benefits and risks of glucocorticoids in rheumatic diseases and other inflammatory joint disorders: new insights from emerging data. An expert consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).

PubMed

Cooper, Cyrus; Bardin, Thomas; Brandi, Maria-Luisa; Cacoub, Patrice; Caminis, John; Civitelli, Roberto; Cutolo, Maurizio; Dere, Willard; Devogelaer, Jean-Pierre; Diez-Perez, Adolfo; Einhorn, Thomas A; Emonts, Patrick; Ethgen, Olivier; Kanis, John A; Kaufman, Jean-Marc; Kvien, Tore K; Lems, Willem F; McCloskey, Eugene; Miossec, Pierre; Reiter, Susanne; Ringe, Johann; Rizzoli, René; Saag, Kenneth; Reginster, Jean-Yves

2016-02-01

This consensus review article considers the question of whether glucocorticoid (GC) therapy is still relevant in the treatment of rheumatic diseases, with a particular focus on rheumatoid arthritis (RA), and whether its side effects can be adequately managed. Recent basic and clinical research on the molecular, cellular and clinical effects of GCs have considerably advanced our knowledge in this field. An overview of the subject seems appropriate. This review is the result of a multidisciplinary expert working group, organised by European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. The recent literature was surveyed and the salient evidence synthetized. The pathophysiological basis of RA (and other inflammatory rheumatic diseases) now strongly implicates the adaptive immune system in addition to innate mechanisms. The molecular effect of GCs and differential GC sensitivity is better understood, although exploiting this knowledge is still in its infancy. The newer treatment strategies of early and aggressive control of RA have gr eatly improved clinical outcomes, but improvements are still possible. Newer targeted anti-inflammatory drugs have made an important impact, yet they too are associated with numerous side effects. Short durations of moderate doses of GCs are generally well tolerated and have a positive benefit/risk ratio. Patients should be assessed for fracture risk and bone preserving agents and be prescribed calcium and vitamin D supplementation. Within a strategy of a disease modifying approach to inflammatory disease, combination therapy including a GC is effective approach.

Procalcitonin as a Diagnostic and Prognostic Factor for Tuberculosis Meningitis

PubMed Central

Kim, Jinseung; Kim, Si Eun; Park, Bong Soo; Shin, Kyong Jin; Ha, Sam Yeol; Park, JinSe; Kim, Sung Eun

2016-01-01

Background and Purpose We investigated the potential role of serum procalcitonin in differentiating tuberculosis meningitis from bacterial and viral meningitis, and in predicting the prognosis of tuberculosis meningitis. Methods This was a retrospective study of 26 patients with tuberculosis meningitis. In addition, 70 patients with bacterial meningitis and 49 patients with viral meningitis were included as the disease control groups for comparison. The serum procalcitonin level was measured in all patients at admission. Differences in demographic and laboratory data, including the procalcitonin level, were analyzed among the three groups. In addition, we analyzed the predictive factors for a prognosis of tuberculosis meningitis using the Glasgow Coma Scale (GCS) at discharge, and the correlation between the level of procalcitonin and the GCS score at discharge. Results Multiple logistic regression analysis showed that a low level of procalcitonin (≤1.27 ng/mL) independently distinguished tuberculosis meningitis from bacterial meningitis. The sensitivity and specificity for distinguishing tuberculosis meningitis from bacterial meningitis were 96.2% and 62.9%, respectively. However, the level of procalcitonin in patients with tuberculosis meningitis did not differ significantly from that in patients with viral meningitis. In patients with tuberculosis meningitis, a high level of procalcitonin (>0.4 ng/mL) was a predictor of a poor prognosis, and the level of procalcitonin was negatively correlated with the GCS score at discharge (r=-0.437, p=0.026). Conclusions We found that serum procalcitonin is a useful marker for differentiating tuberculosis meningitis from bacterial meningitis and is also valuable for predicting the prognosis of tuberculosis meningitis. PMID:27165424

Expression Profiling Identifies Klf15 as a Glucocorticoid Target That Regulates Airway Hyperresponsiveness

PubMed Central

Masuno, Kiriko; Haldar, Saptarsi M.; Jeyaraj, Darwin; Mailloux, Christina M.; Huang, Xiaozhu; Panettieri, Rey A.; Jain, Mukesh K.

2011-01-01

Glucocorticoids (GCs), which activate GC receptor (GR) signaling and thus modulate gene expression, are widely used to treat asthma. GCs exert their therapeutic effects in part through modulating airway smooth muscle (ASM) structure and function. However, the effects of genes that are regulated by GCs on airway function are not fully understood. We therefore used transcription profiling to study the effects of a potent GC, dexamethasone, on human ASM (HASM) gene expression at 4 and 24 hours. After 24 hours of dexamethasone treatment, nearly 7,500 genes had statistically distinguishable changes in expression; quantitative PCR validation of a 40-gene subset of putative GR-regulated genes in 6 HASM cell lines suggested that the early transcriptional targets of GR signaling are similar in independent HASM lines. Gene ontology analysis implicated GR targets in controlling multiple aspects of ASM function. One GR-regulated gene, the transcription factor, Kruppel-like factor 15 (Klf15), was already known to modulate vascular smooth and cardiac muscle function, but had no known role in the lung. We therefore analyzed the pulmonary phenotype of Klf15−/− mice after ovalbumin sensitization and challenge. We found diminished airway responses to acetylcholine in ovalbumin-challenged Klf15−/− mice without a significant change in the induction of asthmatic inflammation. In cultured cells, overexpression of Klf15 reduced proliferation of HASM cells, whereas apoptosis in Klf15−/− murine ASM cells was increased. Together, these results further characterize the GR-regulated gene network in ASM and establish a novel role for the GR target, Klf15, in modulating airway function. PMID:21257922

Early detection of cerebral microbleeds following traumatic brain injury using MRI in the hyper-acute phase.

PubMed

Lawrence, Tim P; Pretorius, Pieter M; Ezra, Martyn; Cadoux-Hudson, Tom; Voets, Natalie L

2017-08-10

Traumatic brain injury (TBI) is a leading cause of death and disability in people under 45. Advanced imaging techniques to identify injury and classify severity in the first few hours and days following trauma could improve patient stratification and aid clinical decision making. Traumatic cerebral microbleeds (TCMBs), detectable on magnetic resonance susceptibility weighted imaging (SWI), can be used as markers of long-term clinical outcome. However, the relationship between TCMBs and injury severity in the first few hours after injury, and their natural evolution, is unknown. We obtained SWI scans in 10 healthy controls, and 13 patients scanned 3-24h following TBI and again at 7-15days. TCMBs were identified and total volume quantified for every lesion in each scan. TCMBs were present in 6 patients, all with more severe injury classified by GCS. No lesions were identified in patients with an initial GCS of 15. Improvement in GCS in the first 15days following injury was significantly associated with a reduction in microbleed volume over the same time-period. MRI is feasible in severely injured patients in the first 24h after trauma. Detection of TCMBs using SWI provides an objective early marker of injury severity following trauma. TCMBs revealed in this time frame, offer the potential to help determine the degree of injury, improving stratification, in order to identify patients who require admission to hospital, transfer to a specialist center, or an extended period of intubation on intensive care. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy

PubMed Central

Curtis, Jeffrey R.; Lindsey, Stephen; Tanaka, Yoshiya; Yamaoka, Kunihiro; Valdez, Hernan; Hirose, Tomohiro; Nduaka, Chudy I.; Wang, Lisy; Mendelsohn, Alan M.; Fan, Haiyun; Chen, Connie; Bananis, Eustratios

2017-01-01

Objective Patients with rheumatoid arthritis (RA) are at increased risk of herpes zoster (HZ), and the risk appears to be increased in patients treated with tofacitinib. The aim of this study was to evaluate whether concomitant treatment with conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) or glucocorticoids (GCs) contributes to the increased risk of HZ in RA patients treated with tofacitinib. Methods HZ cases were identified from the databases of 2 phase I, 9 phase II, 6 phase III, and 2 long‐term extension studies of tofacitinib in RA patients. Crude incidence rates (IRs) of all HZ events (serious and nonserious) per 100 patient‐years (with 95% confidence intervals [95% CIs]) were calculated for unique patients. Within phase III studies, we described HZ rates according to concomitant csDMARD treatment and baseline GC use. A multivariable Cox proportional hazards regression model was used to evaluate HZ risk factors across studies. Results Across all studies (6,192 patients; 16,839 patient‐years), HZ was reported in 636 tofacitinib‐treated patients (IR 4.0, 95% CI 3.7–4.4). In most cases (93%), HZ was classified as nonserious, and the majority of patients (94%) had involvement of only 1 dermatome. HZ IRs varied across regions, from 2.4 (95% CI 2.0–2.9) in Eastern Europe to 8.0 (95% CI 6.6–9.6) in Japan and 8.4 (95% CI 6.4–10.9) in Korea. Within phase III studies, HZ IRs varied according to tofacitinib dose, background csDMARD treatment, and baseline use of GCs. The IRs were numerically lowest for monotherapy with tofacitinib 5 mg twice daily without GCs (IR 0.56 [95% CI 0.07–2.01]) and highest for tofacitinib 10 mg twice daily with csDMARDs and GCs (IR 5.44 [95% CI 3.72–7.68]). Age, GC use, tofacitinib dose, and enrollment within Asia were independent risk factors for HZ. Conclusion Patients receiving treatment with tofacitinib and GCs appear to have a greater risk of developing HZ compared with patients receiving tofacitinib monotherapy without GCs. PMID:28845604

Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy.

PubMed

Winthrop, Kevin L; Curtis, Jeffrey R; Lindsey, Stephen; Tanaka, Yoshiya; Yamaoka, Kunihiro; Valdez, Hernan; Hirose, Tomohiro; Nduaka, Chudy I; Wang, Lisy; Mendelsohn, Alan M; Fan, Haiyun; Chen, Connie; Bananis, Eustratios

2017-10-01

Patients with rheumatoid arthritis (RA) are at increased risk of herpes zoster (HZ), and the risk appears to be increased in patients treated with tofacitinib. The aim of this study was to evaluate whether concomitant treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or glucocorticoids (GCs) contributes to the increased risk of HZ in RA patients treated with tofacitinib. HZ cases were identified from the databases of 2 phase I, 9 phase II, 6 phase III, and 2 long-term extension studies of tofacitinib in RA patients. Crude incidence rates (IRs) of all HZ events (serious and nonserious) per 100 patient-years (with 95% confidence intervals [95% CIs]) were calculated for unique patients. Within phase III studies, we described HZ rates according to concomitant csDMARD treatment and baseline GC use. A multivariable Cox proportional hazards regression model was used to evaluate HZ risk factors across studies. Across all studies (6,192 patients; 16,839 patient-years), HZ was reported in 636 tofacitinib-treated patients (IR 4.0, 95% CI 3.7-4.4). In most cases (93%), HZ was classified as nonserious, and the majority of patients (94%) had involvement of only 1 dermatome. HZ IRs varied across regions, from 2.4 (95% CI 2.0-2.9) in Eastern Europe to 8.0 (95% CI 6.6-9.6) in Japan and 8.4 (95% CI 6.4-10.9) in Korea. Within phase III studies, HZ IRs varied according to tofacitinib dose, background csDMARD treatment, and baseline use of GCs. The IRs were numerically lowest for monotherapy with tofacitinib 5 mg twice daily without GCs (IR 0.56 [95% CI 0.07-2.01]) and highest for tofacitinib 10 mg twice daily with csDMARDs and GCs (IR 5.44 [95% CI 3.72-7.68]). Age, GC use, tofacitinib dose, and enrollment within Asia were independent risk factors for HZ. Patients receiving treatment with tofacitinib and GCs appear to have a greater risk of developing HZ compared with patients receiving tofacitinib monotherapy without GCs. © 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

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

Lin, Dacheng; Irwin, Jimmy A.; Wong, Ka-Wah

We studied the X-ray luminosity function (XLF) of low-mass X-ray binaries (LMXBs) in the nearby lenticular galaxy NGC 3115, using the Megasecond Chandra X-ray Visionary Project Observation. With a total exposure time of ∼1.1 Ms, we constructed the XLF down to a limiting luminosity of ∼10{sup 36} erg s{sup −1}, which is much deeper than that typically reached for other early-type galaxies. We found significant flattening of the overall LMXB XLF from dN/dL ∝ L{sup −2.2±0.4} above 5.5 × 10{sup 37} erg s{sup −1} to dN/dL ∝ L{sup −1.0±0.1} below it, although we could not rule out a fit withmore » a higher break at ∼1.6 × 10{sup 38} erg s{sup −1}. We also found evidence that the XLF of LMXBs in globular clusters (GCs) is overall flatter than that of field LMXBs. Thus, our results for this galaxy do not support the idea that all LMXBs are formed in GCs. The XLF of field LMXBs seems to show spatial variation, with the XLF in the inner region of the galaxy being flatter than that in the outer region, probably due to contamination of LMXBs from undetected and/or disrupted GCs in the inner region. The XLF in the outer region is probably the XLF of primordial field LMXBs, exhibiting dN/dL ∝ L{sup −1.2±0.1} up to a break close to the Eddington limit of neutron star LMXBs (∼1.7 × 10{sup 38} erg s{sup −1}). The break of the GC LMXB XLF is lower, at ∼1.1 × 10{sup 37} erg s{sup −1}. We also confirm previous findings that the metal-rich/red GCs are more likely to host LMXBs than the metal-poor/blue GCs, which is more significant for more luminous LMXBs, and that more massive GCs are more likely to host LMXBs.« less

Gliomatosis cerebri: clinicopathologic study of 33 cases and comparison of mass forming and diffuse types.

PubMed

Park, S; Suh, Y-L; Nam, D-H; Kim, S T

2009-01-01

Gliomatosis cerebri (GC) is defined as a diffuse neoplastic glial cell infiltration of the brain with the preservation of anatomical architecture and the sparing of neurons and can be classified into Type 1 (diffuse) and Type 2 (mass forming) GCs macroscopically. There is little information on subtypes of GC. The aim of this study was to evaluate the clinicopathologic findings of GCs and to compare the clinicopathologic findings between Type 1 and Type 2 GCs. A total of 33 cases of GC were obtained from pathology file of Samsung Medical Center. The diagnosis was based on magnetic resonance imaging findings and histological confirmation for all patients. Fifteen cases were classified into Type 1 and 18 were Type 2 based on the MR images. Clinical information included patients' age, sex, tumor extent, treatment modality and survival. Pathologic features included the amount of rod cells and cytologic anaplasia such as multinucleated tumor giant cells, endothelial cell proliferation, or mitosis. Immunohistochemical study was performed for GFAP, O1, Gal-C, Ki-67, and p53. Clinicopathologic comparison between subtypes and statistical analysis were performed. Median age at diagnosis was older (56 years) in Type 1 than in Type 2 (44 years). Male to female ratio was about 1.54:1. Mean survival time was shorter (21 months) in Type 2 than in Type 1 GCs (24 months) (p = 0.0447). Histologically, 33 cases of GC were classified into two histologic grades (low and high grade) by cytologic anaplasia. High-grade GC was more common in Type 2 than Type 1 (p = 0.027). Immunohistochemical results demonstrated that the infiltrating tumor cells were undifferentiated cells with astrocytic or oligodendroglial differentiation. Ki-67 labeling index was correlated with subtypes (p = 0.0096). Pathologic features were not correlated with survival. Type 1 and 2 GCs are somewhat different in clinical presentation and pathologic features. The age group, survival time, histologic grade, and Ki-67 labeling index were significantly correlated with subtypes ofGCs. Type 2 GC was correlated with poor survival but histologic grade was not.

The Geomechanics of CO 2 Storage in Deep Sedimentary Formations

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

Rutqvist, Jonny

2012-01-12

This study provides a review of the geomechanics and modeling of geomechanics associated with geologic carbon storage (GCS), focusing on storage in deep sedimentary formations, in particular saline aquifers. The paper first introduces the concept of storage in deep sedimentary formations, the geomechanical processes and issues related with such an operation, and the relevant geomechanical modeling tools. This is followed by a more detailed review of geomechanical aspects, including reservoir stress-strain and microseismicity, well integrity, caprock sealing performance, and the potential for fault reactivation and notable (felt) seismic events. Geomechanical observations at current GCS field deployments, mainly at the Inmore » Salah CO 2 storage project in Algeria, are also integrated into the review. The In Salah project, with its injection into a relatively thin, low-permeability sandstone is an excellent analogue to the saline aquifers that might be used for large scale GCS in parts of Northwest Europe, the U.S. Midwest, and China. Some of the lessons learned at In Salah related to geomechanics are discussed, including how monitoring of geomechanical responses is used for detecting subsurface geomechanical changes and tracking fluid movements, and how such monitoring and geomechanical analyses have led to preventative changes in the injection parameters. Recently, the importance of geomechanics has become more widely recognized among GCS stakeholders, especially with respect to the potential for triggering notable (felt) seismic events and how such events could impact the long-term integrity of a CO 2 repository (as well as how it could impact the public perception of GCS). As described in the paper, to date, no notable seismic event has been reported from any of the current CO 2 storage projects, although some unfelt microseismic activities have been detected by geophones. However, potential future commercial GCS operations from large power plants will require injection at a much larger scale. In conclusion, for such large-scale injections, a staged, learn-as-you-go approach is recommended, involving a gradual increase of injection rates combined with continuous monitoring of geomechanical changes, as well as siting beneath a multiple layered overburden for multiple flow barrier protection, should an unexpected deep fault reactivation occur.« less

Constraints on the formation history of the elliptical galaxy NGC 3923 from the colors of its globular clusters

NASA Technical Reports Server (NTRS)

Zepf, Stephen E.; Ashman, Keith M.; Geisler, Doug

1995-01-01

We present a study of the colors of globular clusters associated with the elliptical galaxy NGC 3923. Our final sample consists of Wasington system C and T(sub 1) photometry for 143 globular cluster candidates with an expected contamination of no more than 10%. We find that the color distribution of the NGC 3923 globular cluster system (GCS) is broad and appears to have at least two peaks. A mixture modeling analysis of the color distribution indicates that a two-component model is favored over a single-component one at a high level of confidence (greater than 99%). This evidence for more than one population in the GCS of NGC 3923 is similar to that previously noted for the four other elliptical galaxies for which similar data have been published. Furthermore, we find that the NGC 3923 GCS is redder than the GCSs of previously studed elliptical galaxies of similar luminosity. The median metallicity inferred from our (C-(T(sub 1)))(sub 0) colors is (Fe/H)(sub med) = -0.56, with an uncertainty of 0.14 dex arising from all sources of uncertainty in the mean color. This is more metal rich than the median metallicity found for the GCS of M87 using the same method, (Fe/H)(sub med) = -0.94. Since M87 is more luminous than NGC 3923, this result points to significant scatter about any trend of higher GCS metallicity with increasing galaxy luminosity. We also show that there is a color gradient in the NGC 3923 GCS corresponding to about -0.5 dex in Delta(Fe/H)/Delta(log r). We conclude that the shape of the color distribution of individual GCSs and the variation in mean color among the GCSs of ellipticals are difficult to understand if elliptical galaxies are formed in a single protogalactic collapse. Models in which ellipticals and their globular clusters are formed in more than one event, such as a merger scenario, are more successful in accounting for these observations.

The hunt for new and interesting pulsars with the Green Bank Telescope

NASA Astrophysics Data System (ADS)

Lynch, Ryan Sean

2011-01-01

Pulsars are excellent tools for studying a variety of phenomena in physics and astronomy. Millisecond pulsars (MSPs) are particularly useful because of their clock-like precision and because they are often part of exotic systems. The majority of MSPs have been found in globular clusters (GCs) or in large-area surveys, but most surveys are still sensitivity limited, meaning that many fascinating systems are waiting to be found. A number of technical advances made over the past decade have enabled more sensitive pulsar surveys. This thesis presents the results of several projects with over-arching goals that focused on the discovery and study of new pulsars, with an emphasis on MSPs. Seven new pulsars have been discovered in surveys of 17 GCs, and the majority of these are fully recycled MSPs. These surveys provide insight into which factors influence the total pulsar content of GCs. New timing solutions have been obtained for an additional six GC pulsars that were previously known but not fully characterized; updated solutions are also presented for five well-studied pulsars. Highlights include the discovery of the most massive companion to a fully recycled MSP, and confirmation of a rare, non-recycled GC pulsar. A detailed study of the population of non-recycled pulsars that originate in GCs is also presented, with an emphasis on those pulsars that escape from their host GCs and enter the field of the Galaxy. These results suggest that non-recycled pulsars in GCs are formed via electron capture supernovae, and that these must induce smaller natal kicks than core collapse supernovae. The total population of non-recycled pulsars that have escaped from clusters may be significant, but the chance of identifying them as a separate population is presently small. Finally, early results of the Green Bank Telescope Drift Scan survey are reported. The survey has discovered 26 new pulsars so far, and timing solutions for ten are discussed here, including two recycled pulsars. One of these looks to be an excellent laboratory for studying extreme physics. Future avenues of research are also presented, along with a description of the author's role in education and public outreach projects.

Cluster AgeS Experiment (CASE): deficiency of observed dwarf novae in globular clusters

NASA Astrophysics Data System (ADS)

Pietrukowicz, P.; Kaluzny, J.; Schwarzenberg-Czerny, A.; Thompson, I. B.; Pych, W.; Krzeminski, W.; Mazur, B.

2008-08-01

We present the results of a search for dwarf novae (DNe) in globular clusters (GCs). It is based on the largest available homogeneous sample of observations, in terms of the time-span, number of observations and number of clusters. It includes 16 Galactic GCs and yielded two new certain DNe: M55-CV1 and M22-CV2. All previously known systems located in our fields were recovered, too. We surveyed M4, M5, M10, M12, M22, M30, M55, NGC 288, NGC 362, NGC 2808, NGC 3201, NGC 4372, NGC 6362, NGC 6752, ω Centauri (NGC 5139) and 47 Tucanae (NGC 104). The discovery of two DNe, namely M55-CV1 and M22-CV2, was already reported by Kaluzny et al. and Pietrukowicz et al., respectively. In the remaining 14 GCs, we found no certain new DNe. Our result raises the total number of known DNe in the Galactic GCs to 12 DNe, distributed among seven clusters. Our survey recovered all three already known erupting cataclysmic variables (CVs) located in our fields, namely M5-V101, M22-CV1, and V4 in the foreground of M30. To assess the efficiency of the survey, we analysed images with inserted artificial stars mimicking outbursts of the prototype DNe SS Cygni and U Geminorum. Depending on the conditions, we recovered between 16-100 per cent of these artificial stars. The efficiency seems to be predominantly affected by duty cycle/time-sampling and much less by distance/magnitude. Except for saturated tiny collapsed cores of M30, NGC 362 and NGC 6752 (and also the dense core of NGC 2808), crowding effects in the V band were avoided by our image subtraction technique augmented with auxiliary unsaturated B-band images. Our results clearly demonstrate that in GCs common types of DNe are very rare indeed. However, great care must be taken before these conclusions can be extended to the CV population in GCs.

The Origins of the Ultra Compact Dwarfs in the halos of the central cluster galaxies in Fornax and Virgo

NASA Astrophysics Data System (ADS)

Voggel, Karina Theresia

2015-08-01

Ultra-Compact Dwarf Galaxies (UCDs) have filled the size gap (10-100pc) in the scaling relations of early-type stellar systems. Before their discovery, no objects were known in the parameter space between globular clusters (GCs) and dwarf galaxies. The nature of UCDs is widely debated. Two formation channels have been suggested: either UCDs are surviving nuclei of tidally stripped dwarf galaxies, or they constitute the high mass end of the GC population. In this work we establish new strategies to constrain the formation channel of UCDs, looking for the observational signatures of stripped nuclei.Before falling into a galaxy cluster dwarf galaxies initially host their own GC system. Through tidal interaction the GCs outside of the shrinking tidal radius are lost and disperse in the general GC population of the cluster, whereas GCs inside the tidal radius remain bound to the dwarf galaxy. Therefore, we expect to find some GCs close to the stripped nuclei that have not been removed yet, but dragged towards the nucleus via dynamical friction.We tested this prediction in the halo of NGC 1399, the central Fornax cluster galaxy, where we find a local overabundance of GCs on scales of 0.5 to 1 kpc around UCDs. A similar analysis of GC overdensities around UCDs in the halo of M87, the central Virgo cluster galaxy, is ongoing. Such a clustering signal of GCs around UCDs could be a hint that these UCDs formed as nuclei, and what we see is the remnant GC population of the ancestor galaxy.We also have studied the detailed structural composition of ~100 UCDs in the halo of NGC 1399 by analyzing their surface brightness profiles. We present new evidence for faint asymmetric structures and tidal tails around several UCDs, possible tracers for the assembly history of the central cluster galaxy. With new numbers on the abundance of tidal features and close GC companions within large UCD samples, the contribution of each formation channel to the GC/UCD populations in galaxy halos can be constrained.

Acute effects of local cold therapy in superficial burns on pain, in vivo microcirculation, edema formation and histomorphology.

PubMed

Altintas, B; Altintas, A A; Kraemer, R; Sorg, H; Vogt, P M; Altintas, M A

2014-08-01

Local cold therapy for burns is generally recommended to relief pain and limit tissue damage, however, there is limited data of its physiological benefit. This study aimed to evaluate pathophysiological effects of cold therapy in superficial burn on microcirculation, edema formation, and histomorphology. In 12 volunteers (8f, 4m; aged 30.4±14.1 years) circumscribed superficial burn was induced on both hand back and either left untreated as control (control-group) or treated by local-cold-application (cold-treatment-group). Prior to burn (t0), immediately (t1), 15 min (t2), and 30 min (t3) following cold therapy, following parameter was evaluated using intravital-microscopy; epidermal-thickness (ET), granular-cell-size (GCS), individual-blood-cell-flow (IBCF), and functional-capillary-density (FCD). Both ET and GCS increased significantly more in control-group and slightly in cold-treatment-group in t1, while turns to insignificant t2 onwards. IBCF and FCD raised up in control-group compared to dramatically decrease in cold-treatment-group in t1. In t2 both parameter remains in control-group and increased in cold-treatment-group. Comparison of both groups for IBCF and FCD indicates significant difference in t1 and t2, however, insignificant in t0 and t3. Microcirculation, edema formation, and histomorphology of superficial burn has been significantly influenced through immediate cold therapy, however, this alterations are transient and turns to ineffective after 30 min. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

Adrenal suppression in patients taking inhaled glucocorticoids is highly prevalent and management can be guided by morning cortisol

PubMed Central

Woods, Conor P; Argese, Nicola; Chapman, Matthew; Boot, Christopher; Webster, Rachel; Dabhi, Vijay; Grossman, Ashley B; Toogood, Andrew A; Arlt, Wiebke; Stewart, Paul M; Crowley, Rachel K; Tomlinson, Jeremy W

2015-01-01

Context Up to 3% of US and UK populations are prescribed glucocorticoids (GC). Suppression of the hypothalamo–pituitary–adrenal axis with the potential risk of adrenal crisis is a recognized complication of therapy. The 250 μg short Synacthen stimulation test (SST) is the most commonly used dynamic assessment to diagnose adrenal insufficiency. There are challenges to the use of the SST in routine clinical practice, including both the staff and time constraints and a significant recent increase in Synacthen cost. Methods We performed a retrospective analysis to determine the prevalence of adrenal suppression due to prescribed GCs and the utility of a morning serum cortisol for rapid assessment of adrenal reserve in the routine clinical setting. Results In total, 2773 patients underwent 3603 SSTs in a large secondary/tertiary centre between 2008 and 2013 and 17.9% (n=496) failed the SST. Of 404 patients taking oral, topical, intranasal or inhaled GC therapy for non-endocrine conditions, 33.2% (n=134) had a subnormal SST response. In patients taking inhaled GCs without additional GC therapy, 20.5% (34/166) failed an SST and suppression of adrenal function increased in a dose-dependent fashion. Using receiver operating characteristic curve analysis in patients currently taking inhaled GCs, a basal cortisol ≥348 nmol/l provided 100% specificity for passing the SST; a cortisol value <34 nmol/l had 100% sensitivity for SST failure. Using these cut-offs, 50% (n=83) of SSTs performed on patients prescribed inhaled GCs were unnecessary. Conclusion Adrenal suppression due to GC treatment, particularly inhaled GCs, is common. A basal serum cortisol concentration has utility in helping determine which patients should undergo dynamic assessment of adrenal function. PMID:26294794

Characterization of the velocity anisotropy of accreted globular clusters

NASA Astrophysics Data System (ADS)

Bianchini, P.; Sills, A.; Miholics, M.

2017-10-01

Galactic globular clusters (GCs) are believed to have formed in situ in the Galaxy as well as in dwarf galaxies later accreted on to the Milky Way. However, to date, there is no unambiguous signature to distinguish accreted GCs. Using specifically designed N-body simulations of GCs evolving in a variety of time-dependent tidal fields (describing the potential of a dwarf galaxy-Milky Way merger), we analyse the effects imprinted on the internal kinematics of an accreted GC. In particular, we look at the evolution of the velocity anisotropy. Our simulations show that at early phases, the velocity anisotropy is determined by the tidal field of the dwarf galaxy and subsequently the clusters will adapt to the new tidal environment, losing any signature of their original environment in a few relaxation times. At 10 Gyr, GCs exhibit a variety of velocity anisotropy profiles, namely, isotropic velocity distribution in the inner regions and either isotropy or radial/tangential anisotropy in the intermediate and outer regions. Independent of an accreted origin, the velocity anisotropy primarily depends on the strength of the tidal field cumulatively experienced by a cluster. Tangentially anisotropic clusters correspond to systems that have experienced stronger tidal fields and are characterized by higher tidal filling factor, r50/rj ≳ 0.17, higher mass-loss ≳ 60 per cent and relaxation times trel ≲ 109 Gyr. Interestingly, we demonstrate that the presence of tidal tails can significantly contaminate the measurements of velocity anisotropy when a cluster is observed in projection. Our characterization of the velocity anisotropy profiles in different tidal environments provides a theoretical benchmark for the interpretation of the unprecedented amount of three-dimensional kinematic data progressively available for Galactic GCs.

Plasmodium berghei NK65 in Combination with IFN-γ Induces Endothelial Glucocorticoid Resistance via Sustained Activation of p38 and JNK

PubMed Central

Zielińska, Karolina A.; de Cauwer, Lode; Knoops, Sofie; Van der Molen, Kristof; Sneyers, Alexander; Thommis, Jonathan; De Souza, J. Brian; Opdenakker, Ghislain; De Bosscher, Karolien; Van den Steen, Philippe E.

2017-01-01

Malaria-associated acute respiratory distress syndrome (MA-ARDS) is an often lethal complication of malaria. Currently, no adequate therapy for this syndrome exists. Although glucocorticoids (GCs) have been used to improve clinical outcome of ARDS, their therapeutic benefits remain unclear. We previously developed a mouse model of MA-ARDS, in which dexamethasone treatment revealed GC resistance. In the present study, we investigated GC sensitivity of mouse microvascular lung endothelial cells stimulated with interferon-γ (IFN-γ) and Plasmodium berghei NK65 (PbNK65). Upon challenge with IFN-γ alone, dexamethasone inhibited the expression of CCL5 (RANTES) by 90% and both CCL2 (MCP-1) and CXCL10 (IP-10) by 50%. Accordingly, whole transcriptome analysis revealed that dexamethasone differentially affected several gene clusters and in particular inhibited a large cluster of IFN-γ-induced genes, including chemokines. In contrast, combined stimulation with IFN-γ and PbNK65 extract impaired inhibitory actions of GCs on chemokine release, without affecting the capacity of the GC receptor to accumulate in the nucleus. Subsequently, we investigated the effects of GCs on two signaling pathways activated by IFN-γ. Dexamethasone left phosphorylation and protein levels of signal transducer and activator of transcription 1 (STAT1) unhampered. In contrast, dexamethasone inhibited the IFN-γ-induced activation of two mitogen-activated protein kinases (MAPK), JNK, and p38. However, PbNK65 extract abolished the inhibitory effects of GCs on MAPK signaling, inducing GC resistance. These data provide novel insights into the mechanisms of GC actions in endothelial cells and show how malaria may impair the beneficial effects of GCs. PMID:29033931

Validation of the Chinese version of the FOUR score in the assessment of neurosurgical patients with different level of consciousness.

PubMed

Peng, Juan; Deng, Yingying; Chen, Fangyao; Zhang, Xiaomei; Wang, Xiaoyan; Zhou, Ying; Zhou, Hongzhen; Qiu, Binghui

2015-12-10

The Glasgow Coma Scale (GCS) is currently the most widely used scoring system for comatose patients. A decade ago, the Full Outline of Unresponsiveness (FOUR) score was devised to better capture four functional aspects of consciousness (eye, motor responses, brainstem reflexes, and respiration). This study aimed to validate the Chinese version of the FOUR score in patients with different levels of consciousness. The study had two phases: (1) translation of the FOUR score, and (2) assessment of its reliability and validity. The Chinese version of the FOUR score was developed according to a standardized protocol. One hundred-twenty consecutive patients with acute brain damage, admitted to Nanfang Hospital (Southern Medical University, Guangdong, China) from November 2014 to February 2015, were enrolled. The inter-rater agreement for the FOUR score and GCS was evaluated using intraclass correlation coefficient (ICC). Receiver operating characteristic (ROC) curves were established to determine the scales' abilities to predict outcome. The rater agreement was excellent both for FOUR (ICC = 0.970; p < 0.001) and GCS (ICC = 0.958; p < 0.001). The FOUR score yielded an excellent test-retest reliability (ICC = 0.930; p < 0.001). Spearman's correlation coefficients between GCS and the FOUR score were high: r = 0.932, first rating; r = 0.887, second rating (all p < 0.001). Areas under the curve (AUC) for mortality were 0.834 (95 % CI, 0.740-0.928) and 0.815 (95 % CI, 0.723-0.908) for the FOUR score and GCS, respectively. The Chinese version of the FOUR score is a reliable scale for evaluating the level of consciousness in patients with acute brain injury.

Stellar Population Properties of Ultracompact Dwarfs in M87: A Mass–Metallicity Correlation Connecting Low-metallicity Globular Clusters and Compact Ellipticals

NASA Astrophysics Data System (ADS)

Zhang, Hong-Xin; Puzia, Thomas H.; Peng, Eric W.; Liu, Chengze; Côté, Patrick; Ferrarese, Laura; Duc, Pierre-Alain; Eigenthaler, Paul; Lim, Sungsoon; Lançon, Ariane; Muñoz, Roberto P.; Roediger, Joel; Sánchez-Janssen, Ruben; Taylor, Matthew A.; Yu, Jincheng

2018-05-01

We derive stellar population parameters for a representative sample of ultracompact dwarfs (UCDs) and a large sample of massive globular clusters (GCs) with stellar masses ≳ 106 M ⊙ in the central galaxy M87 of the Virgo galaxy cluster, based on model fitting to the Lick-index measurements from both the literature and new observations. After necessary spectral stacking of the relatively faint objects in our initial sample of 40 UCDs and 118 GCs, we obtain 30 sets of Lick-index measurements for UCDs and 80 for GCs. The M87 UCDs have ages ≳ 8 Gyr and [α/Fe] ≃ 0.4 dex, in agreement with previous studies based on smaller samples. The literature UCDs, located in lower-density environments than M87, extend to younger ages and smaller [α/Fe] (at given metallicities) than M87 UCDs, resembling the environmental dependence of the stellar nuclei of dwarf elliptical galaxies (dEs) in the Virgo cluster. The UCDs exhibit a positive mass–metallicity relation (MZR), which flattens and connects compact ellipticals at stellar masses ≳ 108 M ⊙. The Virgo dE nuclei largely follow the average MZR of UCDs, whereas most of the M87 GCs are offset toward higher metallicities for given stellar masses. The difference between the mass–metallicity distributions of UCDs and GCs may be qualitatively understood as a result of their different physical sizes at birth in a self-enrichment scenario or of galactic nuclear cluster star formation efficiency being relatively low in a tidal stripping scenario for UCD formation. The existing observations provide the necessary but not sufficient evidence for tidally stripped dE nuclei being the dominant contributors to the M87 UCDs.

A role for the gene regulatory module microRNA172/TARGET OF EARLY ACTIVATION TAGGED 1/FLOWERING LOCUS T (miRNA172/TOE1/FT) in the feeding sites induced by Meloidogyne javanica in Arabidopsis thaliana.

PubMed

Díaz-Manzano, Fernando E; Cabrera, Javier; Ripoll, Juan-José; Del Olmo, Iván; Andrés, Mari Fe; Silva, Ana Cláudia; Barcala, Marta; Sánchez, María; Ruíz-Ferrer, Virginia; de Almeida-Engler, Janice; Yanofsky, Martin F; Piñeiro, Manuel; Jarillo, Jose Antonio; Fenoll, Carmen; Escobar, Carolina

2018-01-01

Root knot nematodes (RKNs) penetrate into the root vascular cylinder, triggering morphogenetic changes to induce galls, de novo formed 'pseudo-organs' containing several giant cells (GCs). Distinctive gene repression events observed in early gall/GCs development are thought to be mediated by post-transcriptional silencing via microRNAs (miRNAs), a process that is far from being fully characterized. Arabidopsis thaliana backgrounds with altered activities based on target 35S::MIMICRY172 (MIM172), 35S::TARGET OF EARLY ACTIVATION TAGGED 1 (TOE1)-miR172-resistant (35S::TOE1 R ) and mutant (flowering locus T-10 (ft-10)) lines were used for functional analysis of nematode infective and reproductive parameters. The GUS-reporter lines, MIR172A-E::GUS, treated with auxin (IAA) and an auxin-inhibitor (a-(phenyl ethyl-2-one)-indole-3-acetic acid (PEO-IAA)), together with the MIR172C AuxRE::GUS line with two mutated auxin responsive elements (AuxREs), were assayed for nematode-dependent gene expression. Arabidopsis thaliana backgrounds with altered expression of miRNA172, TOE1 or FT showed lower susceptibility to the RKNs and smaller galls and GCs. MIR172C-D::GUS showed restricted promoter activity in galls/GCs that was regulated by auxins through auxin-responsive factors. IAA induced their activity in galls while PEO-IAA treatment and mutations in AuxRe motifs abolished it. The results showed that the regulatory module miRNA172/TOE1/FT plays an important role in correct GCs and gall development, where miRNA172 is modulated by auxins. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Identifying nearby field T dwarfs in the UKIDSS Galactic Clusters Survey

NASA Astrophysics Data System (ADS)

Lodieu, N.; Burningham, B.; Hambly, N. C.; Pinfield, D. J.

2009-07-01

We present the discovery of two new late-T dwarfs identified in the UKIRT Infrared Deep Sky Survey (UKIDSS) Galactic Clusters Survey (GCS) Data Release 2 (DR2). These T dwarfs are nearby old T dwarfs along the line of sight to star-forming regions and open clusters targeted by the UKIDSS GCS. They are found towards the αPer cluster and Orion complex, respectively, from a search in 54deg2 surveyed in five filters. Photometric candidates were picked up in two-colour diagrams, in a very similar manner to candidates extracted from the UKIDSS Large Area Survey (LAS) but taking advantage of the Z filter employed by the GCS. Both candidates exhibit near-infrared J-band spectra with strong methane and water absorption bands characteristic of late-T dwarfs. We derive spectral types of T6.5 +/- 0.5 and T7 +/- 1 and estimate photometric distances less than 50 pc for UGCS J030013.86+490142.5 and UGCS J053022.52-052447.4, respectively. The space density of T dwarfs found in the GCS seems consistent with discoveries in the larger areal coverage of the UKIDSS LAS, indicating one T dwarf in 6-11deg2. The final area surveyed by the GCS, 1000deg2 in five passbands, will allow expansion of the LAS search area by 25 per cent, increase the probability of finding ultracool brown dwarfs, and provide optimal estimates of contamination by old field brown dwarfs in deep surveys to identify such objects in open clusters and star-forming regions. Based on observations made with the United Kingdom Infrared Telescope, operated by the Joint Astronomy Centre on behalf of the U.K. Science Technology and Facility Council. E-mail: nlodieu@iac.es

Do Staphylococcus epidermidis Genetic Clusters Predict Isolation Sources?

PubMed Central

Tolo, Isaiah; Thomas, Jonathan C.; Fischer, Rebecca S. B.; Brown, Eric L.; Gray, Barry M.

2016-01-01

Staphylococcus epidermidis is a ubiquitous colonizer of human skin and a common cause of medical device-associated infections. The extent to which the population genetic structure of S. epidermidis distinguishes commensal from pathogenic isolates is unclear. Previously, Bayesian clustering of 437 multilocus sequence types (STs) in the international database revealed a population structure of six genetic clusters (GCs) that may reflect the species' ecology. Here, we first verified the presence of six GCs, including two (GC3 and GC5) with significant admixture, in an updated database of 578 STs. Next, a single nucleotide polymorphism (SNP) assay was developed that accurately assigned 545 (94%) of 578 STs to GCs. Finally, the hypothesis that GCs could distinguish isolation sources was tested by SNP typing and GC assignment of 154 isolates from hospital patients with bacteremia and those with blood culture contaminants and from nonhospital carriage. GC5 was isolated almost exclusively from hospital sources. GC1 and GC6 were isolated from all sources but were overrepresented in isolates from nonhospital and infection sources, respectively. GC2, GC3, and GC4 were relatively rare in this collection. No association was detected between fdh-positive isolates (GC2 and GC4) and nonhospital sources. Using a machine learning algorithm, GCs predicted hospital and nonhospital sources with 80% accuracy and predicted infection and contaminant sources with 45% accuracy, which was comparable to the results seen with a combination of five genetic markers (icaA, IS256, sesD [bhp], mecA, and arginine catabolic mobile element [ACME]). Thus, analysis of population structure with subgenomic data shows the distinction of hospital and nonhospital sources and the near-inseparability of sources within a hospital. PMID:27076664

The Next Generation Virgo Cluster Survey (NGVS). XXXII. A Search for Globular Cluster Substructures in the Virgo Galaxy Cluster Core

NASA Astrophysics Data System (ADS)

Powalka, Mathieu; Puzia, Thomas H.; Lançon, Ariane; Longobardi, Alessia; Peng, Eric W.; Duc, Pierre-Alain; Alamo-Martínez, Karla; Blakeslee, John P.; Côté, Patrick; Cuillandre, Jean-Charles; Durrell, Patrick; Eigenthaler, Paul; Ferrarese, Laura; Guhathakurta, Puragra; Gwyn, S. D. J.; Hudelot, Patrick; Liu, Chengze; Mei, Simona; Muñoz, Roberto P.; Roediger, Joel; Sánchez-Janssen, Rubén; Toloba, Elisa; Zhang, Hongxin

2018-03-01

Substructure in globular cluster (GC) populations around large galaxies is expected in galaxy formation scenarios that involve accretion or merger events, and it has been searched for using direct associations between GCs and structure in the diffuse galaxy light, or with GC kinematics. Here, we present a search for candidate substructures in the GC population around the Virgo cD galaxy M87 through the analysis of the spatial distribution of the GC colors. The study is based on a sample of ∼1800 bright GCs with high-quality u, g, r, i, z, K s photometry, selected to ensure a low contamination by foreground stars or background galaxies. The spectral energy distributions of the GCs are associated with formal estimates of age and metallicity, which are representative of its position in a 4D color space relative to standard single stellar population models. Dividing the sample into broad bins based on the relative formal ages, we observe inhomogeneities that reveal signatures of GC substructures. The most significant of these is a spatial overdensity of GCs with relatively young age labels, of diameter ∼0.°1 (∼30 kpc), located to the south of M87. The significance of this detection is larger than about 5σ after accounting for estimates of random and systematic errors. Surprisingly, no large Virgo galaxy is present in this area that could potentially host these GCs. But candidate substructures in the M87 halo with equally elusive hosts have been described based on kinematic studies in the past. The number of GC spectra available around M87 is currently insufficient to clarify the nature of the new candidate substructure.

Arsenic induced progesterone production in a caspase-3-dependent manner and changed redox status in preovulatory granulosa cells.

PubMed

Yuan, Xiao-Hua; Lu, Cai-Ling; Yao, Nan; An, Li-Sha; Yang, Bai-Qing; Zhang, Chuan-Ling; Ma, Xu

2012-01-01

Arsenic contamination is a principal environmental health threat throughout the world. However, little is known about the effect of arsenic on steroidogenesis in granulosa cells (GCs). We found that the treatment of preovulatory GCs with arsenite stimulated progesterone production. A significant increase in serum level of progesterone was observed in female Sprague-Dawley rats following arsenite treatment at a dose of 10 mg/L/rat/day for 7 days. Further experiments demonstrated that arsenite treatment did not change the level of intracellular cyclic AMP (cAMP) or phosphorylated ERK1/2 in preovulatory GCs; however, progesterone production was significantly decreased when cAMP-dependent protein kinase (PKA) or ERK1/2 pathway was inhibited. This implied that the effect of arsenite on progesterone production may require cAMP/PKA and ERK1/2 signaling but not depend on them. Furthermore, we found that arsenite decreased intracellular reactive oxygen species (ROS) but increased the antioxidant glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm) in parallel to the changes in progesterone production. Progesterone antagonist blocked the arsenic-stimulated increase of GSH levels. Arsenite treatment induced caspase-3 activation, although no apoptosis was observed. Inhibition of caspase-3 activity significantly decreased progesterone production stimulated by arsenite or follicle-stimulating hormone (FSH). GSH depletion with buthionine sulfoximine led to cell apoptosis in response to arsenite treatment. Collectively, this study demonstrated for the first time that arsenite stimulates progesterone production through cleaved/active caspase-3-dependent pathway, and the increase of GSH level promoted by progesterone production may protect GCs against apoptosis and maintain the steroidogenesis of GCs in response to arsenite treatment. Copyright © 2011 Wiley Periodicals, Inc.

Tracing the assembly history of NGC 1395 through its Globular Cluster System

NASA Astrophysics Data System (ADS)

Escudero, Carlos G.; Faifer, Favio R.; Smith Castelli, Analía V.; Forte, Juan C.; Sesto, Leandro A.; González, Nélida M.; Scalia, María C.

2018-03-01

We used deep Gemini-South/GMOS g΄r΄i΄z΄ images to study the globular cluster (GC) system of the massive elliptical galaxy NGC 1395, located in the Eridanus supergroup. The photometric analysis of the GC candidates reveals a clear colour bimodality distribution, indicating the presence of `blue' and `red' GC subpopulations. While a negative radial colour gradient is detected in the projected spatial distribution of the red GCs, the blue GCs display a shallow colour gradient. The blue GCs also display a remarkable shallow and extended surface density profile, suggesting a significant accretion of low-mass satellites in the outer halo of the galaxy. In addition, the slope of the projected spatial distribution of the blue GCs in the outer regions of the galaxy, is similar to that of the X-ray halo emission. Integrating up to 165 kpc the profile of the projected spatial distribution of the GCs, we estimated a total GC population and specific frequency of 6000 ± 1100 and SN = 7.4 ± 1.4, respectively. Regarding NGC 1395 itself, the analysis of the deep Gemini/GMOS images shows a low surface brightness umbrella-like structure indicating, at least, one recent merger event. Through relations recently published in the literature, we obtained global parameters, such as Mstellar = 9.32 × 1011 M⊙ and Mh = 6.46 × 1013 M⊙. Using public spectroscopic data, we derive stellar population parameters of the central region of the galaxy by the full spectral fitting technique. We have found that this region seems to be dominated for an old stellar population, in contrast to findings of young stellar populations from the literature.

A pediatric FOUR score coma scale: interrater reliability and predictive validity.

PubMed

Czaikowski, Brianna L; Liang, Hong; Stewart, C Todd

2014-04-01

The Full Outline of UnResponsiveness (FOUR) Score is a coma scale that consists of four components (eye and motor response, brainstem reflexes, and respiration). It was originally validated among the adult population and recently in a pediatric population. To enhance clinical assessment of pediatric intensive care unit patients, including those intubated and/or sedated, at our children's hospital, we modified the FOUR Score Scale for this population. This modified scale would provide many of the same advantages as the original, such as interrater reliability, simplicity, and elimination of the verbal component that is not compatible with the Glasgow Coma Scale (GCS), creating a more valuable neurological assessment tool for the nursing community. Our goal was to potentially provide greater information than the formally used GCS when assessing critically ill, neurologically impaired patients, including those sedated and/or intubated. Experienced pediatric intensive care unit nurses were trained as "expert raters." Two different nurses assessed each subject using the Pediatric FOUR Score Scale (PFSS), GCS, and Richmond Agitation Sedation Scale at three different time points. Data were compared with the Pediatric Cerebral Performance Category (PCPC) assessed by another nurse. Our hypothesis was that the PFSS and PCPC should highly correlate and the GCS and PCPC should correlate lower. Study results show that the PFSS is excellent for interrater reliability for trained nurse-rater pairs and prediction of poor outcome and in-hospital mortality, under various situations, but there were no statistically significant differences between the PFSS and the GCS. However, the PFSS does have the potential to provide greater neurological assessment in the intubated and/or sedated patient based on the outcomes of our study.

Glioma Cell Death Induced by Irradiation or Alkylating Agent Chemotherapy Is Independent of the Intrinsic Ceramide Pathway

PubMed Central

Gramatzki, Dorothee; Herrmann, Caroline; Happold, Caroline; Becker, Katrin Anne; Gulbins, Erich; Weller, Michael; Tabatabai, Ghazaleh

2013-01-01

Background/Aims Resistance to genotoxic therapy is a characteristic feature of glioma cells. Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and glucosylceramide synthase (GCS) catalyzes ceramide metabolism. Increased ceramide levels have been suggested to enhance chemotherapy-induced death of cancer cells. Methods Microarray and clinical data for ASM and GCS in astrocytomas WHO grade II–IV were acquired from the Rembrandt database. Moreover, the glioblastoma database of the Cancer Genome Atlas network (TCGA) was used for survival data of glioblastoma patients. For in vitro studies, increases in ceramide levels were achieved either by ASM overexpression or by the GCS inhibitor DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) in human glioma cell lines. Combinations of alkylating chemotherapy or irradiation and ASM overexpression, PPMP or exogenous ceramide were applied in parental cells. The anti-glioma effects were investigated by assessing proliferation, metabolic activity, viability and clonogenicity. Finally, viability and clonogenicity were assessed in temozolomide (TMZ)-resistant cells upon treatment with PPMP, exogenous ceramide, alkylating chemotherapy, irradiation or their combinations. Results Interrogations from the Rembrandt and TCGA database showed a better survival of glioblastoma patients with low expression of ASM or GCS. ASM overexpression or PPMP treatment alone led to ceramide accumulation but did not enhance the anti-glioma activity of alkylating chemotherapy or irradiation. PPMP or exogenous ceramide induced acute cytotoxicity in glioblastoma cells. Combined treatments with chemotherapy or irradiation led to additive, but not synergistic effects. Finally, no synergy was found when TMZ-resistant cells were treated with exogenous ceramide or PPMP alone or in combination with TMZ or irradiation. Conclusion Modulation of intrinsic glioma cell ceramide levels by ASM overexpression or GCS inhibition does not enhance the anti-glioma activity of alkylating chemotherapy or irradiation. PMID:23667632

High-Altitude, Long-Endurance UAVs vs. Satellites: Potential Benefits for U.S. Army Applications

DTIC Science & Technology

2009-05-01

Refractive Imaging System ....... Point Spread Function ......................... Transmission Characteristics of the Earth’s Atmosphere ...... Scanning...Angle in degrees Commwt Communications Payload Weight p Angular Radius of the Earth in degrees Palbedo Earth’s Albedo Patm Atmospheric Density in...femto-watt (10-15) FY Fiscal Year Gbps Gigabits per Second GBS Global Broadcast System GCS Ground Control Station GEO Geosynchronous Earth Orbit

2007 Western States Fire Mission

NASA Technical Reports Server (NTRS)

Howell, Kathleen

2008-01-01

A general overview of the Ikhana Uninhabited Air System (UAS) is presented. The contents include: 1) Ikhana UAS; 2) Ikhana UAS / Ground Control Station (GCS); 3) Ikhana UAS / Antennas; 4) Western States Fire Mission 2007 Partners; 5) FAA Certificate of Authorization (COA); 6) Western States Fire Missions (WSFM) 2007; 7) WSFM 1-4 2007; 8) California Wildfire Emergency Response 2007; 9) WSFM 5-8 Emergency Response 2007; 10) WSFM Achievements; and 11) WSFM Challenges.

Thermodynamic properties of gas-condensate system with abnormally high content of heavy hydrocarbons

NASA Astrophysics Data System (ADS)

Zanochuev, S. A.; Shabarov, A. B.; Podorozhnikov, S. Yu; Zakharov, A. A.

2018-05-01

Gas-condensate systems (GCS) with an abnormally high content of heavy hydrocarbons are characterized by a sharp change in both phase and component compositions with an insignificant decrease in pressure below the start pressure of the phase transitions (the beginning of condensation). Calculation methods for describing the phase behavior of such systems are very sensitive to the quality of the initial information. The uncertainty of the input data leads not only to significant errors in the forecast of phase compositions, but also to an incorrect phase state estimation of the whole system. The research presents the experimental thermodynamic parameters of the GCS of the BT reservoirs on the Beregovoye field, obtained at the phase equilibrium facility. The data contribute to the adaptation of the calculated models of the phase behavior of the GCS with a change in pressure.

The Ecology of Stress: linking life-history traits with physiological control mechanisms in free-living guanacos

PubMed Central

Jahn, Graciela A.; Soto-Gamboa, Mauricio; Novaro, Andrés J.; Carmanchahi, Pablo

2016-01-01

Background Providing the context for the evolution of life-history traits, habitat features constrain successful ecological and physiological strategies. In vertebrates, a key response to life’s challenges is the activation of the Stress (HPA) and Gonadal (HPG) axes. Much of the interest in stress ecology is motivated by the desire to understand the physiological mechanisms in which the environment affects fitness. As reported in the literature, several intrinsic and extrinsic factors affect variability in hormone levels. In both social and non-social animals, the frequency and type of interaction with conspecifics, as well as the status in social species, can affect HPA axis activity, resulting in changes in the reproductive success of animals. We predicted that a social environment can affect both guanaco axes by increasing the secretion of testosterone (T) and Glucocorticoid (GCs) in response to individual social interactions and the energetic demands of breeding. Assuming that prolonged elevated levels of GCs over time can be harmful to individuals, it is predicted that the HPA axis suppresses the HPG axis and causes T levels to decrease, as GCs increase. Methods All of the data for individuals were collected by non-invasive methods (fecal samples) to address hormonal activities. This is a novel approach in physiological ecology because feces are easily obtained through non-invasive sampling in animal populations. Results As expected, there was a marked adrenal (p-value = .3.4e−12) and gonadal (p-value = 0.002656) response due to seasonal variation in Lama guanicoe. No significant differences were found in fecal GCs metabolites between males/females*season for the entire study period (p-value = 0.2839). Despite the seasonal activity variation in the hormonal profiles, our results show a positive correlation (p-value = 1.952e−11, COR = 0.50) between the adrenal and gonadal system. The marked endocrine (r2 = 0.806) and gonad (r2 = 0.7231) response due to seasonal variation in male guanaco individuals highlights the individual’s energetic demands according to life-history strategies. This is a remarkable result because no inhibition was found between the axes as theory suggests. Finally, the dataset was used to build a reactive scope model for guanacos. Discussion Guanacos cope with the trade-off between sociability and reproductive benefits and costs, by regulating their GCs and T levels on a seasonal basis, suggesting an adaptive role of both axes to different habitat pressures. The results presented here highlight the functional role of stress and gonad axes on a critical phase of a male mammal’s life—the mating period—when all of the resources are at the disposal of the male and must be used to maximize the chances for reproductive success. PMID:27833807

Advanced glycation end products alter steroidogenic gene expression by granulosa cells: an effect partially reversible by vitamin D.

PubMed

Merhi, Z; Buyuk, E; Cipolla, M J

2018-06-01

Does vitamin D attenuate the adverse effects of advanced glycation end products (AGEs) on steroidogenesis by human granulosa cells (GCs)? AGEs alter the expression of genes important in steroidogenesis while 1,25-dihydroxyvitamin D3 (vit D3) in vitro attenuates some of the actions of AGEs on steroidogenic gene expression, possibly by downregulating the expression of the pro-inflammatory cell membrane receptor for AGEs (RAGE). Vitamin D attenuates the pro-inflammatory effects of AGEs in non-ovarian tissues. Women who were undergoing IVF were enrolled. Follicular fluid samples (n = 71) were collected and cumulus GCs (n = 12) were treated in culture. Follicular fluid levels of the anti-inflammatory soluble RAGE (sRAGE), AGEs and 25-hydroxyvitamin D (25-OHD) were quantified for possible correlations. GCs of each participant were split equally and treated with either media alone (control) or with human glycated albumin (HGA as a precursor for AGEs) with or without vit D3 after which RT-PCR and immunofluorescence were performed and cell culture media estradiol (E2) levels were compared. In follicular fluid, sRAGE levels were positively correlated with 25-OHD levels. HGA treatment (i) increased CYP11A1 (by 48%), 3β-HSD (by 38%), StAR (by 42%), CYP17A1 (by 30%) and LHR (by 37%) mRNA expression levels (P < 0.05 for all) but did not alter CYP19A1 or FSHR mRNA expression levels; and (ii) increased E2 release in cell culture media (P = 0.02). Vit D3 treatment (i) downregulated RAGE mRNA expression by 33% and RAGE protein levels by 44% (P < 0.05); (ii) inhibited the HGA-induced increase in CYP11A1, StAR, CYP17A1 and LHR mRNA levels, but not the increase in 3β-HSD mRNA levels; and (iii) did not inhibit the HGA-induced E2 release in cell culture media. This study used luteinized GCs that were collected from women who received gonadotropins thus the results obtained may not fully extrapolate to non-luteinized GCs in vivo. This study suggests that there is a relationship between AGEs and their receptors (RAGE and sRAGE) with vitamin D. Understanding the interaction between AGEs and vitamin D in ovarian physiology could lead to a more targeted therapy for the treatment of ovarian dysfunction. Funding was received from NIH (R01 NS045940), American Society for Reproductive Medicine, Ferring Pharmaceuticals Inc., and University of Vermont College of Medicine Bridge Funds. All authors have nothing to disclose.

Semantic Interpretation of An Artificial Neural Network

DTIC Science & Technology

1995-12-01

ARTIFICIAL NEURAL NETWORK .7,’ THESIS Stanley Dale Kinderknecht Captain, USAF 770 DEAT7ET77,’H IR O C 7... ARTIFICIAL NEURAL NETWORK THESIS Stanley Dale Kinderknecht Captain, USAF AFIT/GCS/ENG/95D-07 Approved for public release; distribution unlimited The views...Government. AFIT/GCS/ENG/95D-07 SEMANTIC INTERPRETATION OF AN ARTIFICIAL NEURAL NETWORK THESIS Presented to the Faculty of the School of Engineering of

Chromium levels in insulin-sensitive tissues and the thigh bone are modulated by prednisolone and high-fat diets in mice.

PubMed

Chen, Po-Wen; Lin, Chang; Chen, Chung-De; Chen, Wen-Ying; Mao, Frank Chiahung

2013-04-01

Glucocorticoids (GCs) are often prescribed in clinics but many adverse effects are also attributed to GCs. It is important to determine the role of GCs in the development of those adverse effects. Here, we investigated the impact of GCs on trivalent chromium (Cr) distribution in animals. Cr has been proposed to be important for proper insulin sensitivity, and deficits may lead to disruption of metabolism. For comparison, the effect of a high-fat diet on Cr modulation was also evaluated. C57BL/6JNarl mice were fed regular or high-fat diets for 12 weeks and further grouped for treatment with prednisolone or saline. Cr levels in tissues were determined 12 h after the treatments. Interestingly, prednisolone treatment led to significantly reduced Cr levels in fat tissue in mice fed regular diets; compared to the high-fat diet alone, prednisolone plus the high-fat diet led to a further reduction in Cr levels in the liver, muscle, and fat. Notably, a single dose of prednisolone was linked with elevated Cr levels in the thigh bones of mice fed by either regular or high-fat diets. In conclusion, this report has provided evidence that prednisolone in combination with a high-fat diet effects modulation of Cr levels in selected tissues.

Property-based design of a glucosylceramide synthase inhibitor that reduces glucosylceramide in the brain[S

PubMed Central

Larsen, Scott D.; Wilson, Michael W.; Abe, Akira; Shu, Liming; George, Christopher H.; Kirchhoff, Paul; Showalter, H. D. Hollis; Xiang, Jianming; Keep, Richard F.; Shayman, James A.

2012-01-01

Synthesis inhibition is the basis for the treatment of type 1 Gaucher disease by the glucosylceramide synthase (GCS) inhibitor eliglustat tartrate. However, the extended use of eliglustat and related compounds for the treatment of glycosphingolipid storage diseases with CNS manifestations is limited by the lack of brain penetration of this drug. Property modeling around the D-threo-1-phenyl-2-decanoylamino-3-morpholino-propanol (PDMP) pharmacophore was employed in a search for compounds of comparable activity against the GCS but lacking P-glycoprotein (MDR1) recognition. Modifications of the carboxamide N-acyl group were made to lower total polar surface area and rotatable bond number. Compounds were screened for inhibition of GCS in crude enzyme and whole cell assays and for MDR1 substrate recognition. One analog, 2-(2,3-dihydro-1H-inden-2-yl)-N-((1R,2R)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2-yl)acetamide (CCG-203586), was identified that inhibited GCS at low nanomolar concentrations with little to no apparent recognition by MDR1. Intraperitoneal administration of this compound to mice for 3 days resulted in a significant dose dependent decrease in brain glucosylceramide content, an effect not seen in mice dosed in parallel with eliglustat tartrate. PMID:22058426

Metabolomic Responses of Guard Cells and Mesophyll Cells to Bicarbonate

PubMed Central

Misra, Biswapriya B.; de Armas, Evaldo; Tong, Zhaohui; Chen, Sixue

2015-01-01

Anthropogenic CO2 presently at 400 ppm is expected to reach 550 ppm in 2050, an increment expected to affect plant growth and productivity. Paired stomatal guard cells (GCs) are the gate-way for water, CO2, and pathogen, while mesophyll cells (MCs) represent the bulk cell-type of green leaves mainly for photosynthesis. We used the two different cell types, i.e., GCs and MCs from canola (Brassica napus) to profile metabolomic changes upon increased CO2 through supplementation with bicarbonate (HCO3 -). Two metabolomics platforms enabled quantification of 268 metabolites in a time-course study to reveal short-term responses. The HCO3 - responsive metabolomes of the cell types differed in their responsiveness. The MCs demonstrated increased amino acids, phenylpropanoids, redox metabolites, auxins and cytokinins, all of which were decreased in GCs in response to HCO3 -. In addition, the GCs showed differential increases of primary C-metabolites, N-metabolites (e.g., purines and amino acids), and defense-responsive pathways (e.g., alkaloids, phenolics, and flavonoids) as compared to the MCs, indicating differential C/N homeostasis in the cell-types. The metabolomics results provide insights into plant responses and crop productivity under future climatic changes where elevated CO2 conditions are to take center-stage. PMID:26641455

Disruptions in follicle cell functions in the ovaries of rhesus monkeys during summer

PubMed Central

VandeVoort, Catherine A.; Mtango, Namdori R.; Midic, Uros

2015-01-01

Oocytes isolated from female rhesus monkeys following standard ovarian stimulation protocols during the summer months displayed a reduced capacity to mature compared with stimulation during the normal breeding season. Because the gene expression profiles of oocyte-associated cumulus cells and mural granulosa cells (CCs and GCs) are indicative of altered oocyte quality and can provide insight into intrafollicular processes that may be disrupted during oogenesis, we performed array-based transcriptome comparisons of CCs and GCs from summer and normal breeding season stimulation cycles. Summer CCs and GCs both display deficiencies in expression of mRNAs related to cell proliferation, angiogenesis, and endocrine signaling, as well as reduced expression of glycogen phosphorylase. Additionally, CCs display deficiencies in expression of mRNAs related to stress response. These results provide the first insight into the specific molecular pathways and processes that are disrupted in the follicles of rhesus macaque females during the summer season. Some of the changes seen in summer GCs and CCs have been reported in humans and in other model mammalian species. This suggests that the seasonal effects seen in the rhesus monkey may help us to understand better the mechanisms that contribute to reduced oocyte quality and fertility in humans. PMID:25586978

Intermediate-Mass Black Holes in Globular Cluster Systems

NASA Astrophysics Data System (ADS)

Wrobel, J. M.; Miller-Jones, J. C. A.; Nyland, K. E.; Maccarone, T. J.

2018-01-01

Theory suggests that globular clusters (GCs) of stars can host intermediate-mass black holes (IMBHs) with masses of about 100 to 100,000 solar masses. We invoke a semi-empirical model to predict the mass of an IMBH that, if undergoing accretion in the long-lived hard X-ray state, is consistent with the synchrotron radio luminosity of a GC. We apply this model to extant images from the Karl G. Jansky Very Large Array (VLA) and to simulated images from the Next Generation Very Large Array (ngVLA). Guided by our VLA results for M81's system of 206 probable GCs at a distance of 3.6 Mpc, we consider using the ngVLA to study the hundreds of globular cluster systems out to a distance of 25 Mpc. With its sensitivity, spatial resolution, and field of view, we conclude that the ngVLA at 2cm will efficiently probe IMBH masses for tens of thousands of GCs. Finding IMBHs in GCs could validate a formation channel for seed BHs in the early universe, underpin gravitational wave predictions for space missions, and test scaling relations between stellar systems and the central BHs they host. The NRAO is a facility of the NSF, operated under cooperative agreement by AUI, Inc.

STMN1 Promotes Progesterone Production Via StAR Up-regulation in Mouse Granulosa Cells.

PubMed

Dou, Yun-De; Zhao, Han; Huang, Tao; Zhao, Shi-Gang; Liu, Xiao-Man; Yu, Xiao-Chen; Ma, Zeng-Xiang; Zhang, Yu-Chao; Liu, Tao; Gao, Xuan; Li, Lei; Lu, Gang; Chan, Wai-Yee; Gao, Fei; Liu, Hong-Bin; Chen, Zi-Jiang

2016-06-08

Stathmin 1 (STMN1) is a biomarker in several types of neoplasms. It plays an important role in cell cycle progression, mitosis, signal transduction and cell migration. In ovaries, STMN1 is predominantly expressed in granulosa cells (GCs). However, little is known about the role of STMN1 in ovary. In this study, we demonstrated that STMN1 is overexpressed in GCs in patients with polycystic ovary syndrome (PCOS). In mouse primary GCs, the overexpression of STMN1 stimulated progesterone production, whereas knockdown of STMN1 decreased progesterone production. We also found that STMN1 positively regulates the expression of Star (steroidogenic acute regulatory protein) and Cyp11a1 (cytochrome P450 family 11 subfamily A member 1). Promoter and ChIP assays indicated that STMN1 increased the transcriptional activity of Star and Cyp11a1 by binding to their promoter regions. The data suggest that STMN1 mediates the progesterone production by modulating the promoter activity of Star and Cyp11a1. Together, our findings provide novel insights into the molecular mechanisms of STMN1 in ovary GC steroidogenesis. A better understanding of this potential interaction between STMN1 and Star in progesterone biosynthesis in GCs will facilitate the discovery of new therapeutic targets in PCOS.

Alleviation of Rosup-induced oxidative stress in porcine granulosa cells by anthocyanins from red-fleshed apples.

PubMed

Xiang, Ya; Lai, Fangnong; He, Guifang; Li, Yapeng; Yang, Leilei; Shen, Wei; Huo, Heqiang; Zhu, Jun; Dai, Hongyi; Zhang, Yugang

2017-01-01

Anthocyanins are the polyphenolic phytochemicals which have been shown to scavenge free radicals. In this study, we investigated the effects of anthocyanins extracted from red-fleshed apples (Malus sieversii) on reducing oxidative damage by Rosup in porcine granulosa cells (GCs) by measuring intracellular reactive oxygen species (ROS), content of glutathione (GSH), activities of superoxide dismutase (SOD1), catalase (CAT) and glutathione peroxidase (GPX1) and the gene expression of SOD1, CAT, GPX1. Apoptosis was determined with TdT-mediated dUTP-biotin nick end labeling (TUNEL) and apoptosis-related proteins were quantified with Western blotting. The results indicate that Rosup increases oxidative stress by inducing reactive oxygen species production in porcine GCs and the oxidative stress could be reduced by anthocyanins. The gene expression of SOD1, CAT, GPX1 and the activities of these enzymes were increased when GCs were treated with anthocyanins and Rosup for 6 hours. Anthocyanins inhibit Rosup-induced apoptosis by increasing expression of antiapoptotic protein Bcl-2 and suppressing the expression of pro-apoptotic protein Bax. Collectively, anthocyanins from red-fleshed apples reduce oxidative stress and inhibit apoptosis in porcine GCs in vitro. This approach indicates that antioxidants might be developed from red-fleshed apples.

Predictive value of the APACHE II, SAPS II, SOFA and GCS scoring systems in patients with severe purulent bacterial meningitis.

PubMed

Pietraszek-Grzywaczewska, Iwona; Bernas, Szymon; Łojko, Piotr; Piechota, Anna; Piechota, Mariusz

2016-01-01

Scoring systems in critical care patients are essential for predicting of the patient outcome and evaluating the therapy. In this study, we determined the value of the Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), Sequential Organ Failure Assessment (SOFA) and Glasgow Coma Scale (GCS) scoring systems in the prediction of mortality in adult patients admitted to the intensive care unit (ICU) with severe purulent bacterial meningitis. We retrospectively analysed data from 98 adult patients with severe purulent bacterial meningitis who were admitted to the single ICU between March 2006 and September 2015. Univariate logistic regression identified the following risk factors of death in patients with severe purulent bacterial meningitis: APACHE II, SAPS II, SOFA, and GCS scores, and the lengths of ICU stay and hospital stay. The independent risk factors of patient death in multivariate analysis were the SAPS II score, the length of ICU stay and the length of hospital stay. In the prediction of mortality according to the area under the curve, the SAPS II score had the highest accuracy followed by the APACHE II, GCS and SOFA scores. For the prediction of mortality in a patient with severe purulent bacterial meningitis, SAPS II had the highest accuracy.

Alleviation of Rosup-induced oxidative stress in porcine granulosa cells by anthocyanins from red-fleshed apples

PubMed Central

He, Guifang; Li, Yapeng; Yang, Leilei; Shen, Wei; Huo, Heqiang; Zhu, Jun; Dai, Hongyi

2017-01-01

Anthocyanins are the polyphenolic phytochemicals which have been shown to scavenge free radicals. In this study, we investigated the effects of anthocyanins extracted from red-fleshed apples (Malus sieversii) on reducing oxidative damage by Rosup in porcine granulosa cells (GCs) by measuring intracellular reactive oxygen species (ROS), content of glutathione (GSH), activities of superoxide dismutase (SOD1), catalase (CAT) and glutathione peroxidase (GPX1) and the gene expression of SOD1, CAT, GPX1. Apoptosis was determined with TdT-mediated dUTP-biotin nick end labeling (TUNEL) and apoptosis-related proteins were quantified with Western blotting. The results indicate that Rosup increases oxidative stress by inducing reactive oxygen species production in porcine GCs and the oxidative stress could be reduced by anthocyanins. The gene expression of SOD1, CAT, GPX1 and the activities of these enzymes were increased when GCs were treated with anthocyanins and Rosup for 6 hours. Anthocyanins inhibit Rosup-induced apoptosis by increasing expression of antiapoptotic protein Bcl-2 and suppressing the expression of pro-apoptotic protein Bax. Collectively, anthocyanins from red-fleshed apples reduce oxidative stress and inhibit apoptosis in porcine GCs in vitro. This approach indicates that antioxidants might be developed from red-fleshed apples. PMID:28850606

Effect of SeptimebTM as a new natural extract on severe sepsis: A randomized clinical trial.

PubMed

Pourdast, Alieh; Sanaei, Maryam; Jafari, Sirous; Mohammadi, Mostafa; Khalili, Hossein; Shafiee, Gita; Ahadi, Zeinab; Rostami, Mahsa; Alizad, Saba; Heshmat, Ramin; Mohraz, Minoo

2017-01-01

Septimeb as a herbal medicine has regulatory effects on inflammation. This study set to evaluate the effects of Septimeb among patients with sepsis on inflammatory biomarkers and survival rate. In this randomized clinical trial, 51 patients with sepsis from the ICU and medical ward of Imam Khomeini Hospital were divided into two groups: Septimeb (n=25) and control group (n=26). In the control group, the patients received a standard treatment only for 7 days, while Septimeb group received Septimeb (6cc vial with 500cc serum glucose infusion 5% daily for one to two hours) plus standard treatment of sepsis for 7 days. Then, blood samples were analyzed. APACHE (Acute Physiologic and Chronic Health Evaluation), SOFA (Sequential Organ Failure Assessment), and GCS (Glasgow Coma Score) values were calculated daily. Treatment with Septimeb showed a significant decrease in SOFA value (1.54±0.83) compared to the control group (2.39±0.88) (P<0.001) and a significant increase in GCS value (14.46±0.88) compared to the control group (12.86±1.78) (P<0.001). Improvements of these values can confirm the potential of Septimeb in the reduction of severity of sepsis (P<0.05). There were significant decreases in lactate and blood sugar and WBC levels. In addition, inflammatory factors such as ESR (Septimeb group: 52.07±34.80, control group: 51.75±42.10, P=0.98) and CRP (Septimeb group: 48.86±23.21, control group: 49.93±36.22, P=0.92) decreased, but did not show a significant reduction. Septimeb has positive effects on reduction of the severity of sepsis which leads to reduction of patients' mortality rates.

Effect of SeptimebTM as a new natural extract on severe sepsis: A randomized clinical trial

PubMed Central

Pourdast, Alieh; Sanaei, Maryam; Jafari, Sirous; Mohammadi, Mostafa; Khalili, Hossein; Shafiee, Gita; Ahadi, Zeinab; Rostami, Mahsa; Alizad, Saba; Heshmat, Ramin; Mohraz, Minoo

2017-01-01

Background: Septimeb as a herbal medicine has regulatory effects on inflammation. This study set to evaluate the effects of Septimeb among patients with sepsis on inflammatory biomarkers and survival rate. Methods: In this randomized clinical trial, 51 patients with sepsis from the ICU and medical ward of Imam Khomeini Hospital were divided into two groups: Septimeb (n=25) and control group (n=26). In the control group, the patients received a standard treatment only for 7 days, while Septimeb group received Septimeb (6cc vial with 500cc serum glucose infusion 5% daily for one to two hours) plus standard treatment of sepsis for 7 days. Then, blood samples were analyzed. APACHE (Acute Physiologic and Chronic Health Evaluation), SOFA (Sequential Organ Failure Assessment), and GCS (Glasgow Coma Score) values were calculated daily. Results: Treatment with Septimeb showed a significant decrease in SOFA value (1.54±0.83) compared to the control group (2.39±0.88) (P<0.001) and a significant increase in GCS value (14.46±0.88) compared to the control group (12.86±1.78) (P<0.001). Improvements of these values can confirm the potential of Septimeb in the reduction of severity of sepsis (P<0.05). There were significant decreases in lactate and blood sugar and WBC levels. In addition, inflammatory factors such as ESR (Septimeb group: 52.07±34.80, control group: 51.75±42.10, P=0.98) and CRP (Septimeb group: 48.86±23.21, control group: 49.93±36.22, P=0.92) decreased, but did not show a significant reduction. Conclusion: Septimeb has positive effects on reduction of the severity of sepsis which leads to reduction of patients’ mortality rates. PMID:28503281

Cerebrospinal Fluid Markers of Macrophage and Lymphocyte Activation after Traumatic Brain Injury in Children

PubMed Central

Newell, Elizabeth; Shellington, David K.; Simon, Dennis W.; Bell, Michael J.; Kochanek, Patrick M.; Feldman, Keri; Bayır, Hülya; Aneja, Rajesh K.; Carcillo, Joseph A.; Clark, Robert S. B.

2015-01-01

Objective The magnitude and role of the cellular immune response following pediatric traumatic brain injury (TBI) remains unknown. We tested the hypothesis that macrophage/microglia and T-cell activation occurs following pediatric TBI by measuring cerebrospinal fluid (CSF) levels of sCD163 and ferritin, and sIL-2Rα, respectively, and determined whether these biomarkers were associated with relevant clinical variables and outcome. Design Retrospective analysis of samples from an established, single-center CSF bank. Setting Pediatric Intensive Care Unit (PICU) in a tertiary Children’s Hospital Patients Sixty-six pediatric patients after severe TBI (Glasgow coma scale score [GCS]<8) age 1 mo-16 y and 17 control patients age 1 mo-14 y. Measurements and Main Results CSF levels of sCD163, ferritin, and sIL-2Rα were determined by ELISA at 2 time points (t1=17±10, t2=72±15 h) for each TBI patient. CSF sCD163, ferritin, and sIL2Rα levels after TBI were compared with controls and analyzed for associations with age, patient sex, initial GCS, diagnosis of abusive head trauma (AHT), the presence of hemorrhage on computerized tomography scan, and Glasgow outcome scale score (GOS). CSF sCD163 was increased in TBI patients at t2 vs. t1 and controls (95.4[21.8–134.0] vs. 31.0[5.7–77.7] and 27.8[19.1–43.1] ng/ml, respectively; median[IQ]; P<0.05). CSF ferritin was increased in TBI patients at t2 and t1 vs. controls (8.3[7.5–19.8] and 8.9[7.5–26.7] vs. [7.5[0.0–0.0] ng/ml, respectively; P<0.05). CSF sIL-2Rα in TBI patients at t2 and t1 were not different vs. controls. Multivariate regression revealed associations between high ferritin and age ≤ 4 y, lower GCS, AHT, and unfavorable GOS. Conclusions Children with TBI demonstrate evidence for macrophage activation after TBI, and in terms of CSF ferritin, this appears more prominent with young age, initial injury severity, AHT, and unfavorable outcome. Further study is needed to determine whether biomarkers of macrophage activation may be used to discriminate between aberrant and adaptive immune responses, and whether inflammation represents a therapeutic target after TBI. PMID:25850867

Optogenetic Modulation and Multi-Electrode Analysis of Cerebellar Networks In Vivo

PubMed Central

Kruse, Wolfgang; Krause, Martin; Aarse, Janna; Mark, Melanie D.; Manahan-Vaughan, Denise; Herlitze, Stefan

2014-01-01

The firing patterns of cerebellar Purkinje cells (PCs), as the sole output of the cerebellar cortex, determine and tune motor behavior. PC firing is modulated by various inputs from different brain regions and by cell-types including granule cells (GCs), climbing fibers and inhibitory interneurons. To understand how signal integration in PCs occurs and how subtle changes in the modulation of PC firing lead to adjustment of motor behaviors, it is important to precisely record PC firing in vivo and to control modulatory pathways in a spatio-temporal manner. Combining optogenetic and multi-electrode approaches, we established a new method to integrate light-guides into a multi-electrode system. With this method we are able to variably position the light-guide in defined regions relative to the recording electrode with micrometer precision. We show that PC firing can be precisely monitored and modulated by light-activation of channelrhodopsin-2 (ChR2) expressed in PCs, GCs and interneurons. Thus, this method is ideally suited to investigate the spatio/temporal modulation of PCs in anesthetized and in behaving mice. PMID:25144735

A Critical Review of the Impacts of Leaking CO 2 Gas and Brine on Groundwater Quality

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

Qafoku, Nikolla; Zheng, Liange; Bacon, Diana H.

2015-09-30

Geological carbon sequestration (GCS) is a global carbon emission reduction strategy involving the capture of CO 2 emitted from fossil fuel burning power plants, as well as the subsequent injection of the captured CO 2 gas into deep saline aquifers or depleted oil and gas reservoirs. A critical question that arises from the proposed GCS is the potential impacts of CO 2 injection on the quality of drinking-water systems overlying CO 2 sequestration storage sites. Although storage reservoirs are evaluated and selected based on their ability to safely and securely store emplaced fluids, leakage of CO 2 from storage reservoirsmore » is a primary risk factor and potential barrier to the widespread acceptance of geologic CO 2 sequestration (OR Harvey et al. 2013; Y-S Jun et al. 2013; DOE 2007). Therefore, a systematic understanding of how CO 2 leakage would affect the geochemistry of potable aquifers, and subsequently control or affect elemental and contaminant release via sequential and/or simultaneous abiotic and biotic processes and reactions is vital.« less

Integrated cockpit display and processor: the best solution for Link-16 applications

NASA Astrophysics Data System (ADS)

Smeyne, Alan L.; Savaya, John

2000-08-01

Link-16 Data Link systems are being added to current avionics systems to provide increased situational awareness and command data. By using a single intelligent display system, the impact to existing aircraft systems to implement Link-16 capabilities is minimized. Litton Guidance & Control Systems (G&CS), a military avionics supplier for more than forty years, provides Open System Architecture (OSA), large screen aircraft display systems. Based on a common set of plug-in modules, these Smart Multi-Function Displays (SMFD) are available in a variety of sizes and processing capabilities, any one of which can meet the Link-16 requirements. Using a single smart SMFD connected to a Link-16 subsystem has many advantages. With digital moving map capability, the SMFD can monitor and display air and ground tracks of both friendly and hostile forces while providing potential threat data to the operator. The SMFD can also monitor vehicle status and mission data to share between friendly air and surface forces. To support the integrated digital battlefield, Link-16 capability is required and the Litton G&CS SMFD provides the processing/display functionality to implement this capability.

Pulse Coupled Neural Networks for the Segmentation of Magnetic Resonance Brain Images.

DTIC Science & Technology

1996-12-01

PULSE COUPLED NEURAL NETWORKS FOR THE SEGMENTATION OF MAGNETIC RESONANCE BRAIN IMAGES THESIS Shane Lee Abrahamson First Lieutenant, USAF AFIT/GCS/ENG...COUPLED NEURAL NETWORKS FOR THE SEGMENTATION OF MAGNETIC RESONANCE BRAIN IMAGES THESIS Shane Lee Abrahamson First Lieutenant, USAF AFIT/GCS/ENG/96D-01...research develops an automated method for segmenting Magnetic Resonance (MR) brain images based on Pulse Coupled Neural Networks (PCNN). MR brain image

Low Level Laser Therapy for Traumatic Brain Injury

DTIC Science & Technology

2015-10-01

resonance imaging as the primary outcome measure. The second objective is a series of preclinical (mouse) investigations to decipher the mechanisms of LLLT...abnormal imaging (matching DoD definition of moderate TBI) and an anticipated hospital admission of 3 days or longer. We ran the study with these...moderate TBIs fall within the GCS13-15 with abnormal imaging category (instead of GCS9-12). These patients are typically admitted to the ED

[Clinical efficacy observation of acupuncture at suliao (GV 25) on improving regain of consciousness from coma in severe craniocerebral injury].

PubMed

Xu, Kai-Sheng; Song, Jian-Hua; Huang, Tiao-Hua; Huang, Zhi-Hua; Yu, Lu-Chang; Zheng, Wei-Ping; Chen, Xiao-Shan; Liu, Chuan

2014-06-01

To compare the clinical therapeutic effects differences between acupuncture at Suliao (GV 25) and Shuigou (GV 26) on promoting regain of consciousness from coma in severe craniocerebral injury. Based on regular emergency treatments of neurosurgery, eighty-two cases of craniocerebral injury who were under stable condition were randomly divided into an observation group (42 cases) and a control group (40 cases). Suliao (GV 25) was selected as main aupoint, while Laogong (PC 8) and Yongquan (KI 1), etc. were selected as adjuvant acupoints and Neiguan (PC 6), Sanyinjiao (SP 6), Yifeng (TE 17) and Wangu (GB 12), etc. were selected as matching acupoints in the observation group where a strong needle manipulation was applied to improve the regain of consciousness. The main acupoint of Shuigou (GV 26) along with identical adjuvant acupoints and matching acupoints in the observation group were selected in the control group with identical strong needle manipulation. The treatment was given once a day in both groups, five times per week and ten times were considered as one session. The immediate clinical symptoms after acupuncture at Suliao (GV 25) and Shuigou (GV 26) were observed as well as Glasgow coma scale (GCS) before the treatment, after 45 days and 90 days of treatment to assess the resuscitation time and rate. Also the clinical efficacy was compared between both groups. The occurrence rate of sneezing reflex was 85.7% (36/42) in the observation group, which was higher than 25.0% (10/40) in the control group (P < 0.01). The average resuscitation time was (64.6 +/- 19.4) days in the observation group, which was obviously shorter than (73.8 +/- 14. 6) days in the control group (P < 0.05). The resuscitation rate was 88.1% (37/42) in the observation group, which was similar to 75.0% (30/40) in the control group (P > 0.05). Compared before the treatment, GCS were both improved after the treatment in two groups (both P < 0.01). The 90-day GCS was 9.52 +/- 2.32 in the observation group, which was superior to 8.47 +/-2.14 in the control group (P < 0.05). The curative and markedly effective rate was 45.2% (19/42) in the observation group, which was superior to 22.5% (9/40) in the control group (P < 0.05). The effect of acupuncture at Suliao (GV 25) on improving regain of consciousness from coma in severe craniocerebral injury is positive. It could specifically improve sneezing reflex and stimulate respiratory center, which has more obvious effect than acupuncture at Shuigou (GV 26).

A frequency-domain seismic blind deconvolution based on Gini correlations

NASA Astrophysics Data System (ADS)

Wang, Zhiguo; Zhang, Bing; Gao, Jinghuai; Huo Liu, Qing

2018-02-01

In reflection seismic processing, the seismic blind deconvolution is a challenging problem, especially when the signal-to-noise ratio (SNR) of the seismic record is low and the length of the seismic record is short. As a solution to this ill-posed inverse problem, we assume that the reflectivity sequence is independent and identically distributed (i.i.d.). To infer the i.i.d. relationships from seismic data, we first introduce the Gini correlations (GCs) to construct a new criterion for the seismic blind deconvolution in the frequency-domain. Due to a unique feature, the GCs are robust in their higher tolerance of the low SNR data and less dependent on record length. Applications of the seismic blind deconvolution based on the GCs show their capacity in estimating the unknown seismic wavelet and the reflectivity sequence, whatever synthetic traces or field data, even with low SNR and short sample record.

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

Brewster, S.B.

The U.S. Department of Energy's Remote Sensing Laboratory developed the geometric correction system (GCS) as a state-of-the-art solution for removing distortions from multispectral line scanner data caused by aircraft motion. The system operates on Daedalus AADS-1268 scanner data acquired from fixed-wing and helicopter platforms. The aircraft attitude, altitude, acceleration, and location are recorded and applied to the data, thereby determining the location of the earth with respect to a given datum and projection. The GCS has yielded a positional accuracy of 0.5 meters when used with a 1-meter digital elevation model. Data at this level of accuracy are invaluable inmore » making precise areal estimates and as input into a geographic information system. The combination of high-spatial resolution and accurate geo-rectification makes the GCS a unique tool in identifying and locating environmental conditions, finding targets of interest, and detecting changes as they occur over time.« less

Actions of Brain-Derived Neurotrophic Factor and Glucocorticoid Stress in Neurogenesis

PubMed Central

Numakawa, Tadahiro; Odaka, Haruki; Adachi, Naoki

2017-01-01

Altered neurogenesis is suggested to be involved in the onset of brain diseases, including mental disorders and neurodegenerative diseases. Neurotrophic factors are well known for their positive effects on the proliferation/differentiation of both embryonic and adult neural stem/progenitor cells (NSCs/NPCs). Especially, brain-derived neurotrophic factor (BDNF) has been extensively investigated because of its roles in the differentiation/maturation of NSCs/NPCs. On the other hand, recent evidence indicates a negative impact of the stress hormone glucocorticoids (GCs) on the cell fate of NSCs/NPCs, which is also related to the pathophysiology of brain diseases, such as depression and autism spectrum disorder. Furthermore, studies including ours have demonstrated functional interactions between neurotrophic factors and GCs in neural events, including neurogenesis. In this review, we show and discuss relationships among the behaviors of NSCs/NPCs, BDNF, and GCs. PMID:29099059

Warranties in Weapon System Procurement: An Analysis of Practice and Theory.

DTIC Science & Technology

1987-04-01

MICROCOPY RESOLUTION TEST CHART NATIONAL BUREAU OF SIANDARDS 1963 A fD r ILE GW cm AD-A190 933 IDA PAPER P-2024 WARRANTIES IN WEAPON SYSTEM PROCUREMENT...EPWT Essential Performance Warranty Test FAR Federal Acquisition Regulation GCS Guidance Control Section GLD Ground Laser Locator Designator GS General...Service IDA Institute for Defense Analyses I&L Installations and Logistics IPT Initial Production Test LDR Laser Designator Rangefimder MLDT Mean

Glutathione metabolic status in the aged rabbit aorta.

PubMed

Lapenna, Domenico; Ciofani, Giuliano; Giamberardino, Maria Adele

2017-05-01

It is not known whether aging alters glutathione metabolic status of the mammalian arterial tissue favoring vascular oxidative stress and dysfunction. Thus we assessed total, reduced and oxidized glutathione (TG, GSH and GSSG, respectively), the glutathione redox ratio (GRR, namely [GSSG]/[GSH+2GSSG]×100), and the activities of the glutathione status-regulating enzymes glutathione reductase (GSSG-Red), γ-glutamylcysteine synthetase (γ-GCS) and γ-glutamyl transpeptidase (γ-GT) in the aortic tissue of 9 young adult control rabbits (YACR, about 4months old) and 9 aged rabbits (AR, about 4.5years old); aortic lipid and protein oxidation and H 2 O 2 were also determined as oxidative stress indicators. Vascular function was assessed on aortic ring preparations. TG and GSH concentrations, together with γ-GCS and γ-GT activities, were significantly lower, while GSSG content and the GRR higher, in the AR than in the YACR aortas; GSSG-Red activity did not differ significantly between the two groups. Heightened levels of lipid and protein oxidation and H 2 O 2 occurred in the AR aortas, indicating age-dependent vascular oxidative stress. Moreover, in the whole population of 18 rabbits, the aortic values of GSH and related enzyme activities were inversely and significantly correlated with those of lipid and protein oxidation and H 2 O 2 , highlighting the antioxidant role of GSH and related enzymes in the vascular tissue. Aortic endothelium-dependent vasodilation was lower in the AR than in the YACR. In conclusion, glutathione metabolic status is altered in the aged rabbit aorta reflecting depressed γ-GCS- and γ-GT-related GSH biosynthesis and GSSG burden eventually favoring vascular oxidative stress and dysfunction. Copyright © 2017 Elsevier Inc. All rights reserved.

Antenatal corticosteroids alter insulin signaling pathways in fetal baboon skeletal muscle.

PubMed

Blanco, Cynthia L; Moreira, Alvaro G; McGill-Vargas, Lisa L; Anzueto, Diana G; Nathanielsz, Peter; Musi, Nicolas

2014-05-01

We hypothesize that prenatal exposure to glucocorticoids (GCs) negatively alters the insulin signal transduction pathway and has differing effects on the fetus according to gestational age (GA) at exposure. Twenty-three fetal baboons were delivered from 23 healthy, nondiabetic mothers. Twelve preterm (0.67 GA) and 11 near-term (0.95 GA) baboons were killed immediately after delivery. Half of the pregnant baboons at each gestation received two doses of i.m. betamethasone 24 h apart (170 μg/kg) before delivery, while the other half received no intervention. Vastus lateralis muscle was obtained from postnatal animals to measure the protein content and gene expression of insulin receptor β (IRβ; INSR), IRβ Tyr 1361 phosphorylation (pIRβ), IR substrate 1 (IRS1), IRS1 tyrosine phosphorylation (pIRS1), p85 subunit of PI3-kinase, AKT (protein kinase B), phospho-AKT Ser473 (pAKT), AKT1, AKT2, and glucose transporters (GLUT1 and GLUT4). Skeletal muscle from preterm baboons exposed to GCs had markedly reduced protein content of AKT and AKT1 (respectively, 73 and 72% from 0.67 GA control, P<0.001); IRβ and pIRβ were also decreased (respectively, 94 and 85%, P<0.01) in the muscle of premature GC-exposed fetuses but not in term fetuses. GLUT1 and GLUT4 tended to increase with GC exposure in preterm animals (P=0.09), while GLUT4 increased sixfold in term animals after exposure to GC (P<0.05). In conclusion, exposure to a single course of antenatal GCs during fetal life alters the insulin signaling pathway in fetal muscle in a manner dependent on the stage of gestation.

VizieR Online Data Catalog: 5 Galactic GC proper motions from Gaia DR1 (Watkins+, 2017)

NASA Astrophysics Data System (ADS)

Watkins, L. L.; van der Marel, R. P.

2017-11-01

We present a pilot study of Galactic globular cluster (GC) proper motion (PM) determinations using Gaia data. We search for GC stars in the Tycho-Gaia Astrometric Solution (TGAS) catalog from Gaia Data Release 1 (DR1), and identify five members of NGC 104 (47 Tucanae), one member of NGC 5272 (M3), five members of NGC 6121 (M4), seven members of NGC 6397, and two members of NGC 6656 (M22). By taking a weighted average of member stars, fully accounting for the correlations between parameters, we estimate the parallax (and, hence, distance) and PM of the GCs. This provides a homogeneous PM study of multiple GCs based on an astrometric catalog with small and well-controlled systematic errors and yields random PM errors similar to existing measurements. Detailed comparison to the available Hubble Space Telescope (HST) measurements generally shows excellent agreement, validating the astrometric quality of both TGAS and HST. By contrast, comparison to ground-based measurements shows that some of those must have systematic errors exceeding the random errors. Our parallax estimates have uncertainties an order of magnitude larger than previous studies, but nevertheless imply distances consistent with previous estimates. By combining our PM measurements with literature positions, distances, and radial velocities, we measure Galactocentric space motions for the clusters and find that these also agree well with previous analyses. Our analysis provides a framework for determining more accurate distances and PMs of Galactic GCs using future Gaia data releases. This will provide crucial constraints on the near end of the cosmic distance ladder and provide accurate GC orbital histories. (4 data files).

The anti-Müllerian hormone (AMH) induces forkhead box L2 (FOXL2) expression in primary culture of human granulosa cells in vitro.

PubMed

Sacchi, Sandro; Marinaro, Federica; Xella, Susanna; Marsella, Tiziana; Tagliasacchi, Daniela; La Marca, Antonio

2017-09-01

Anti-Müllerian hormone (AMH) and forkhead box L2 (FOXL2) are two pivotal genes expressed in human granulosa cells (hGCs) where both genes share similar inhibitory functions on activation and follicular growth in order to preserve the ovarian follicle reserve. Furthermore, AMH and FOXL2 contribute to inhibit steroidogenesis, decreasing or preventing the activation of gonadotrophin-dependent aromatase CYP19A1 cytochrome P450 family 19 subfamily A member 1 (CYP19A1). The purpose of this study is to evaluate the role of AMH in regulating the expression of FOXL2. Primary cultures of hGCs were treated with increasing concentrations of recombinant human AMH (rhAMH; range 10-100 ng/ml) for 3 h. Negative controls were performed using corresponding amounts of AMH vehicle. Total RNA or proteins were purified and quantified by spectrophotometry. FOXL2 and CYP19A1 gene expression, normalized by reference gene ribosomal protein S7 (RpS7), was evaluated by RT-qPCR. Each reaction was repeated in triplicate. Statistical analysis was performed. Extracted proteins were analyzed by immunoblot using anti-FOXL2 and anti-β-actin as primary antibodies. rhAMH treatments tested did not modulate the basal expression of aromatase CYP19A1 gene. rhAMH (50 ng/ml) was able to increase FOXL2 gene expression and its intracellular content. This study demonstrated the existence of an AMH-FOXL2 relationship in hGCs. AMH is capable of increasing both gene and protein expression of FOXL2. Because FOXL2 induces AMH transcription, these ovarian factors could be finely regulated by a positive feedback loop mechanism to preserve the ovarian follicle reserve.

γ-Glutamylcysteine synthetase (γ-GCS) as a target for overcoming chemo- and radio-resistance of human hepatocellular carcinoma cells.

PubMed

Lin, Li-Ching; Chen, Chi-Fen; Ho, Chun-Te; Liu, Jun-Jen; Liu, Tsan-Zon; Chern, Chi-Liang

2018-04-01

This study uncovered that the genetically endowed intracellular glutathione contents (iGSH) regulated by the catalytic subunit of γ‑glutamylcysteine synthetase heavy chain (γ‑GCSh) as a prime target for overcoming both the inherited and stimuli-activated chemo- and radio-resistance of hepatocellular carcinoma (HCC) cells. Reactive oxygen species (ROS) production and mitochondrial membrane potential (Δψm) were determined by the probe-based flow cytometry. The TUNEL assay was used as an index of radio-sensitivity and the MTT assay was used as an index of chemo-sensitivity against various anti-cancer agents. iGSH and γ‑GCSh activity were measured by HPLC methods. γ‑GCSh-overexpressing GCS30 cell line was established by tetracycline-controlled Tet-OFF gene expression system in SK-Hep-1 cells. The relative radio-sensitivities of a panel of five HCC cells were found to be correlated negatively with both the contents of iGSH and their corresponding γ‑GCSh activities with an order of abundance being Hep G2 > Hep 3B > J5 > Mahlavu > SK-Hep-1, respectively. Similarly, the cytotoxicity response patterns of these HCC cells against arsenic trioxide (ATO), a ROS-producing anti-cancer drug, were exactly identical to the order of ranking instigated by the radiotherapy (RT) treatment. Next, γ‑GCSh-overexpressing GCS30 cells were found to possess excellent ability to profoundly mitigate both the drop of Δψm and apoptotic TUNEL-positive cell population engendered by ATO, cisplatin, doxorubicin, and RT treatments. Our data unequivocally demonstrate that γ‑GCSh may represent a prime target for overcoming anti-cancer drugs and RT resistance for HCC cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Tycho- Gaia Astrometric Solution Parallaxes and Proper Motions for Five Galactic Globular Clusters

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

Watkins, Laura L.; Van der Marel, Roeland P., E-mail: lwatkins@stsci.edu

2017-04-20

We present a pilot study of Galactic globular cluster (GC) proper motion (PM) determinations using Gaia data. We search for GC stars in the Tycho- Gaia Astrometric Solution (TGAS) catalog from Gaia Data Release 1 (DR1), and identify five members of NGC 104 (47 Tucanae), one member of NGC 5272 (M3), five members of NGC 6121 (M4), seven members of NGC 6397, and two members of NGC 6656 (M22). By taking a weighted average of member stars, fully accounting for the correlations between parameters, we estimate the parallax (and, hence, distance) and PM of the GCs. This provides a homogeneousmore » PM study of multiple GCs based on an astrometric catalog with small and well-controlled systematic errors and yields random PM errors similar to existing measurements. Detailed comparison to the available Hubble Space Telescope ( HST ) measurements generally shows excellent agreement, validating the astrometric quality of both TGAS and HST . By contrast, comparison to ground-based measurements shows that some of those must have systematic errors exceeding the random errors. Our parallax estimates have uncertainties an order of magnitude larger than previous studies, but nevertheless imply distances consistent with previous estimates. By combining our PM measurements with literature positions, distances, and radial velocities, we measure Galactocentric space motions for the clusters and find that these also agree well with previous analyses. Our analysis provides a framework for determining more accurate distances and PMs of Galactic GCs using future Gaia data releases. This will provide crucial constraints on the near end of the cosmic distance ladder and provide accurate GC orbital histories.« less

Glucocorticoid activity and metabolism with NaCl-induced low-grade metabolic acidosis and oral alkalization: results of two randomized controlled trials.

PubMed

Buehlmeier, Judith; Remer, Thomas; Frings-Meuthen, Petra; Maser-Gluth, Christiane; Heer, Martina

2016-04-01

Low-grade metabolic acidosis (LGMA), as induced by high dietary acid load or sodium chloride (NaCl) intake, has been shown to increase bone and protein catabolism. Underlying mechanisms are not fully understood, but from clinical metabolic acidosis interactions of acid-base balance with glucocorticoid (GC) metabolism are known. We aimed to investigate GC activity/metabolism under alkaline supplementation and NaCl-induced LGMA. Eight young, healthy, normal-weight men participated in two crossover designed interventional studies. In Study A, two 10-day high NaCl diet (32 g/d) periods were conducted, one supplemented with 90 mmol KHCO3/day. In Study B, participants received a high and a low NaCl diet (31 vs. 3 g/day), each for 14 days. During low NaCl, the diet was moderately acidified by replacement of a bicarbonate-rich mineral water (consumed during high NaCl) with a non-alkalizing drinking water. In repeatedly collected 24-h urine samples, potentially bioactive-free GCs (urinary-free cortisol + free cortisone) were analyzed, as well as tetrahydrocortisol (THF), 5α-THF, and tetrahydrocortisone (THE). With supplementation of 90 mmol KHCO3, the marker of total adrenal GC secretion (THF + 5α-THF + THE) dropped (p = 0.047) and potentially bioactive-free GCs were reduced (p = 0.003). In Study B, however, GC secretion and potentially bioactive-free GCs did not exhibit the expected fall with NaCl-reduction as net acid excretion was raised by 30 mEq/d. Diet-induced acidification/alkalization affects GC activity and metabolism, which in case of long-term ingestion of habitually acidifying western diets may constitute an independent risk factor for bone degradation and cardiometabolic diseases.

Wide-Field HST Observations of the Globular Cluster System in NGC 1399

NASA Astrophysics Data System (ADS)

Puzia, Thomas H.; Paolillo, Maurizio; Goudfrooij, Paul; Maccarone, Thomas J.; Fabbiano, Giuseppina; Angelini, Lorella

2014-01-01

We present a comprehensive high spatial-resolution imaging study of globular clusters (GCs) in NGC 1399, the central giant elliptical cD galaxy in the Fornax galaxy cluster, obtained with HST/ACS. Using a novel technique to construct drizzled PSF libraries for HST/ACS data, we accurately determine the GC half-light radius, r_h, for the major fraction of the NGC 1399 GC system and find a trend of increasing r_h versus galactocentric distance, R_gal, out to ~10 kpc and a flat relation beyond. This trend is very similar for blue and red GCs which are found to have a mean size ratio of r_h(red)/r_h(blue)=0.82+/-0.11 at all R_gal from the core regions of the galaxy out to ~40 kpc. This suggests that the size difference between blue and red GCs is due to internal mechanisms related to the evolution of their constituent stellar populations. Modeling the stellar mass density profile of NGC 1399 derived from its surface brightness profile shows that additional external dynamical mechanisms are required to limit the GC size in the galaxy halo regions. We suggest that this may be realized by an exotic GC orbit distribution function, an extended dark matter halo, and/or tidal stress induced by the increased stochasticity in the dwarf halo substructure at larger galactocentric radii. We compare our results with the GC r_h distribution functions in various galaxies and find that the fraction of extended GCs is systematically larger in late-type galaxies compared with GC systems in early-type galaxies. This is likely due to the dynamically more violent evolution of early-type galaxies. We match our GC r_h measurements with radial velocity data from the literature and split the resulting sample at the median r_h value into compact and extended GCs. We find that compact GCs show a significantly smaller line-of-sight velocity dispersion, 225+/-25 km/s, than their extended counterparts, 317+/-21 km/s. Considering the weaker statistical correlation in the GC r_h-color and the GC r_h-R_gal relations, the more significant GC size-dynamics relation appears to be astrophysically more relevant and hints at the dominant influence of the GC orbit distribution function on the evolution of GC structural parameters.

Wide-Field Hubble Space Telescope Observations of the Globular Cluster System in NGC 1399*

NASA Technical Reports Server (NTRS)

Puzia, Thomas H.; Paolillo, Maurizio; Goudfrooij, Paul; Maccarone, Thomas J.; Fabbiano, Giuseppina; Angelini, Lorella

2014-01-01

We present a comprehensive high spatial resolution imaging study of globular clusters (GCs) in NGC 1399, thecentral giant elliptical cD galaxy in the Fornax galaxy cluster, conducted with the Advanced Camera for Surveys(ACS) aboard theHubble Space Telescope(HST).Using a novel technique to construct drizzled point-spreadfunction libraries for HSTACS data, we accurately determine the fidelity of GC structural parameter measurementsfrom detailed artificial star cluster experiments and show the superior robustness of the GC half-light radius,rh,compared with other GC structural parameters, such as King core and tidal radius. The measurement ofrhfor themajor fraction of the NGC 1399 GC system reveals a trend of increasingrhversus galactocentric distance,Rgal,out to about 10 kpc and a flat relation beyond. This trend is very similar for blue and red GCs, which are found tohave a mean size ratio ofrh,redrh,blue0.820.11 at all galactocentric radii from the core regions of the galaxyout to40 kpc. This suggests that the size difference between blue and red GCs is due to internal mechanismsrelated to the evolution of their constituent stellar populations. Modeling the mass density profile of NGC 1399shows that additional external dynamical mechanisms are required to limit the GC size in the galaxy halo regionstorh2 pc. We suggest that this may be realized by an exotic GC orbit distribution function, an extended darkmatter halo, andor tidal stress induced by the increased stochasticity in the dwarf halo substructure at largergalactocentric distances. We compare our results with the GCrhdistribution functions in various galaxies and findthat the fraction of extended GCs withrh5 pc is systematically larger in late-type galaxies compared with GCsystems in early-type galaxies. This is likely due to the dynamically more violent evolution of early-type galaxies.We match our GCrhmeasurements with radial velocity data from the literature and split the resulting sample at themedianrhvalue into compact and extended GCs. We find that compact GCs show a significantly smaller line-of-sight velocity dispersion,cmp22525 km s1, than their extended counterparts,ext31721 km s1.Considering the weaker statistical correlation in the GCrhcolor and the GCrhRgalrelations, the more significantGC sizedynamics relation appears to be astrophysically more relevant and hints at the dominant influence of theGC orbit distribution function on the evolution of GC structural parameters.

ON THE BIRTH MASSES OF THE ANCIENT GLOBULAR CLUSTERS

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

Conroy, Charlie; Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA

All globular clusters (GCs) studied to date show evidence for internal (star-to-star) variation in their light-element abundances (including Li, C, N, O, F, Na, Mg, Al, and probably He). These variations have been interpreted as evidence for multiple star formation episodes within GCs, with secondary episodes fueled, at least in part, by the ejecta of asymptotic giant branch (AGB) stars from a first generation of stars. A major puzzle emerging from this otherwise plausible scenario is that the fraction of stars associated with the second episode of star formation is observed to be much larger than expected for a standardmore » initial mass function. The present work investigates this tension by modeling the observed anti-correlation between [Na/Fe] and [O/Fe] for 20 Galactic GCs. If the abundance pattern of the retained AGB ejecta does not depend on GC mass at fixed [Fe/H], then a strong correlation is found between the fraction of current GC stellar mass composed of pure AGB ejecta, f{sub p} , and GC mass. This fraction varies from 0.20 at low masses (10{sup 4.5} M{sub Sun }) to 0.45 at high masses (10{sup 6.5} M{sub Sun }). The fraction of mass associated with pure AGB ejecta is directly related to the total mass of the cluster at birth; the ratio between the initial and present mass in stars can therefore be derived. Assuming a star formation efficiency of 50%, the observed Na-O anti-correlations imply that GCs were at least 10-20 times more massive at birth, a conclusion that is in qualitative agreement with previous work. These factors are lower limits because any mass-loss mechanism that removes first- and second-generation stars equally will leave f{sub p} unchanged. The mass dependence of f{sub p} probably arises because lower mass GCs are unable to retain all of the AGB ejecta from the first stellar generation. Recent observations of elemental abundances in intermediate-age Large Magellanic Cloud clusters are re-interpreted and shown to be consistent with this basic scenario. The small scatter in f{sub p} at fixed GC mass argues strongly that the process responsible for the large mass loss is internal to GCs. A satisfactory explanation of these trends is currently lacking.« less

Sodium abundances of AGB and RGB stars in Galactic globular clusters. II. Analysis and results of NGC 104, NGC 6121, and NGC 6809

NASA Astrophysics Data System (ADS)

Wang, Y.; Primas, F.; Charbonnel, C.; Van der Swaelmen, M.; Bono, G.; Chantereau, W.; Zhao, G.

2017-11-01

Aims: We investigate the Na abundance distribution of asymptotic giant branch (AGB) stars in Galactic globular clusters (GCs) and its possible dependence on GC global properties, especially age and metallicity. Methods: We analyze high-resolution spectra of a large sample of AGB and red giant branch (RGB) stars in the Galactic GCs NGC 104, NGC 6121, and NGC 6809 obtained with FLAMES/GIRAFFE at ESO/VLT, and determine their Na abundances. This is the first time that the AGB stars in NGC 6809 are targeted. Moreover, to investigate the dependence of AGB Na abundance dispersion on GC parameters, we compare the AGB [Na/H] distributions of a total of nine GCs, with five determined by ourselves with homogeneous method and four from literature, covering a wide range of GC parameters. Results: NGC 104 and NGC 6809 have comparable AGB and RGB Na abundance distributions revealed by the K-S test, while NGC 6121 shows a lack of very Na-rich AGB stars. By analyzing all nine GCs, we find that the Na abundances and multiple populations of AGB stars form complex picture. In some GCs, AGB stars have similar Na abundances and/or second-population fractions as their RGB counterparts, while some GCs do not have Na-rich second-population AGB stars, and various cases exist between the two extremes. In addition, the fitted relations between fractions of the AGB second population and GC global parameters show that the AGB second-population fraction slightly anticorrelates with GC central concentration, while no robust dependency can be confirmed with other GC parameters. Conclusions: Current data roughly support the prediction of the fast-rotating massive star (FRMS) scenario. However, considering the weak observational and theoretical trends where scatter and exceptions exist, the fraction of second-population AGB stars can be affected by more than one or two factors, and may even be a result of stochasticity. Based on observations made with ESO telescopes at the La Silla Paranal Observatory under programme ID 093.D-0818(A).Full Tables 3, 5, and 7 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/607/A135

Prevalence and impact of diffuse axonal injury in patients with moderate and severe head injury: a cohort study of early magnetic resonance imaging findings and 1-year outcome.

PubMed

Skandsen, Toril; Kvistad, Kjell Arne; Solheim, Ole; Strand, Ingrid Haavde; Folvik, Mari; Vik, Anne

2010-09-01

In this prospective cohort study the authors examined patients with moderate to severe head injuries using MR imaging in the early phase. The objective was to explore the occurrence of diffuse axonal injury (DAI) and determine whether DAI was related to level of consciousness and patient outcome. One hundred and fifty-nine patients (age range 5-65 years) with traumatic brain injury, who survived the acute phase, and who had a Glasgow Coma Scale (GCS) score of 3-13 were admitted between October 2004 and August 2008. Of these 159 patients, 106 were examined using MR imaging within 4 weeks postinjury. Patients were classified into 1 of 3 stages of DAI: Stage 1, in which lesions were confined to the lobar white matter; Stage 2, in which there were callosal lesions; and Stage 3, in which lesions occurred in the dorsolateral brainstem. The outcome measure used 12 months postinjury was the Glasgow Outcome Scale-Extended (GOSE). Diffuse axonal injury was detected in 72% of the patients and a combination of DAI and contusions or hematomas was found in 50%. The GCS score was significantly lower in patients with "pure DAI" (median GCS Score 9) than in patients without DAI (median GCS Score 12; p < 0.001). The GCS score was related to outcome only in those patients with DAI (r = 0.47; p = 0.001). Patients with DAI had a median GOSE score of 7, and patients without DAI had a median GOSE score of 8 (p = 0.10). Outcome was better in patients with DAI Stage 1 (median GOSE Score 8) and DAI Stage 2 (median GOSE Score 7.5) than in patients with DAI Stage 3 (median GOSE Score 4; p < 0.001). Thus, in patients without any brainstem injury, there was no difference in good recovery between patients with DAI (67%) and patients without DAI (66%). Diffuse axonal injury was found in almost three-quarters of the patients with moderate and severe head injury who survived the acute phase. Diffuse axonal injury influenced the level of consciousness, and only in patients with DAI was GCS score related to outcome. Finally, DAI was a negative prognostic sign only when located in the brainstem.

Matrix metalloproteinase 9 and cellular fibronectin plasma concentrations are predictors of the composite endpoint of length of stay and death in the intensive care unit after severe traumatic brain injury

PubMed Central

2012-01-01

Background The relationship between severe traumatic brain injury (TBI) and blood levels of matrix metalloproteinase-9 (MMP-9) or cellular fibronectin (c-Fn) has never been reported. In this study, we aimed to assess whether plasma concentrations of MMP-9 and c-Fn could have predictive values for the composite endpoint of intensive care unit (ICU) length of stay (LOS) of survivors and mortality after severe TBI. Secondary outcomes were the state of consciousness measured with the Glasgow Coma Scale (GCS) of survivors at 14 days and Glasgow Outcome Scale Extended (GOSE) at 3 months. Methods Forty-nine patients with abbreviated injury scores of the head region ≥ 4 were included. Blood was sampled at 6, 12, 24 and 48 hours after injury. MMP-9 and c-Fn concentrations were measured by ELISA. The values of MMP-9 and c-Fn, and, for comparison, the value of the GCS on the field of the accident (fGCS), as predictors of the composite outcome of ICU LOS and death were assessed by logistic regression. Results There was a linear relationship between maximal MMP-9 concentration, measured during the 6-12-hour period, and maximal c-Fn concentration, measured during the 24-48-hour period. The risk of staying longer than 9 days in the ICU or of dying was increased in patients with a maximal early MMP-9 concentration ≥ 21.6 ng/ml (OR = 5.0; 95% CI: 1.3 to 18.6; p = 0.02) or with a maximal late c-Fn concentration ≥ 7.7 μg/ml (OR = 5.4; 95% CI: 1.4 to 20.8; p = 0.01). A similar risk association was observed with fGCS ≤8 (OR, 4.4; 95% CI, 1.2-15.8; p = 0.02). No relationship was observed between MMP-9, c-Fn concentrations or fGCS and the GCS at 14 days of survivors and GOSE at 3 months. Conclusions Plasma MMP-9 and c-Fn concentrations in the first 48 hours after injury are predictive for the composite endpoint of ICU LOS and death after severe TBI but not for consciousness at 14 days and outcome at 3 months. PMID:23249478

Total and ionized plasma magnesium concentrations in children after traumatic brain injury.

PubMed

Mendez, Donna Reyes; Corbett, Ronald; Macias, Charles; Laptook, Abbot

2005-03-01

This study examined 1) whether plasma total Mg (TMg) and ionized Mg (IMg) concentrations in children are reduced by traumatic brain injury (TBI) and 2) whether the extent of reduction correlates with severity of trauma assessed by the Glasgow Coma Scale (GSC) score. This was a prospective cohort study of 98 pediatric patients who had TBI and were admitted through the emergency department. A GCS score was assigned and blood was obtained upon presentation and 24 h later. Plasma was analyzed for TMg and IMg. Patients were grouped into three categories-GCS scores 13-15, 8-12, and <8-to designate mild (n=21), moderate (n=37), and severe (n=40) TBI, respectively. Blood was obtained from 50 healthy children before elective surgery as controls. Control subjects had a TMg and an IMg of 0.94 +/- 0.08 and 0.550 +/- 0.06 mM. TBI patients had an initial TMg and IMg of 0.83 +/- 0.09 and 0.520 +/- 0.05 mM, respectively. Initial TMg for mild, moderate, and severe TBI subgroups (0.87 +/- 0.16, 0.81 +/- 0.15, and 0.83 +/- 0.14 mM, respectively) was reduced from control subjects (p <0.01). IMg was reduced only in the severe TBI subgroup (0.516 +/- 0.07 mM; p=0.016). Twenty-four hours later, TMg remained lower than in control subjects for all subgroups of TBI; however, IMg normalized. TBI in children is associated with a reduction in TMg, whereas IMg decreased only with severe TBI. IMg returned to control values by 24 h despite a continued lower TMg, suggesting mechanisms to maintain IMg. Changes in plasma IMg may serve as a marker for TBI but only over a limited time interval.

[Concentration of proinflammatory cytokines (TNF-alpha, IL-8) in the cerebrospinal fluid and the course of bacterial meningitis].

PubMed

Bociaga-Jasik, Monika; Garlicki, Aleksander; Kalinowska-Nowak, Anna; Mach, Tomasz

2004-01-01

Bacterial meningitis is still associated with high mortality rate and severe neurological sequels. The aim of the study was to assess correlation between concentration of proinflammatory cytokines (TNF-alpha, IL-1 beta, IL-8) in the cerebrospinal fluid (CSF) and patient condition described on the basis of Glasgow Coma Scale (GCS), changes in the CSF (pleocytosis, protein and glucose level), mortality rate and occurrence of neurological complications. 42 patients with bacterial meningitis have been analysed. Control group consisted of 25 patients with viral meningitis and 23 patients without meningitis. In analysed group with bacterial meningitis the correlation between number of scores aggregated by patients in GCS and outcome has been observed. Concentration of TNF-alpha, IL-1 beta, IL-8 in CSF of patient with bacterial meningitis was significantly higher (mean value; 705.2 pg/ml, 401.1 pg/ml and 1696.0 pg/ml) than in control group (viral meningitis: 7.93 pg/ml, 31.89 pg/ml, 405.28 pg/ml, without meningitis: 0.38 pg/ml, 2.55 pg/ml, 32.56 pg/ml). Negative correlation between concentration of investigated cytokines in the CSF of patient with bacterial meningitis and GCS has been observed. Furthermore TNF-alpha and IL-8 levels correlated with pleocytosis, and protein and glucose levels, whereas IL-1 beta correlated with pleocytosis and protein level in CSF. Connection between TNF-alpha and IL-1 beta but not IL-8 level and outcome of bacterial meningitis has been observed. High TNF-alpha in the CSF (median value 953 pg/ml) was associated with significant risk of patient death. IL-1 beta has been better prognostic indicator. Patients who developed neurological sequels had median value of IL-1 beta level 401.3 pg/ml, and those who died had 585.9 pg/ml vs 244.7 pg/ml in the group who survived without any complications. Analysis of the ROC curve-revealed, that concentration of IL-1 beta > or = 289.9 pg/ml with 88.9% sensitivity and 67.7% specifity differentiate cases who at risk for death. For TNF-alpha the cut-off was > or = 538.9 pg/ml. The sensitivity for determined critical point was 77%, and specificity was 68.7%. Our investigation confirm that TNF alpha, IL-1 beta, IL-8 are useful in differential diagnosis of neuroinfections. Assessment of patients with bacterial meningitis on the basis of GCS is helpful to establish prognosis, and CGS seems to correlate with the intensity of inflammation in the CSF. High concentration of TNF-alpha, and IL-1 beta in the CSF are associated with the risk of patient death during the course of bacterial meningitis, but IL-1 beta has been the better prognostic marker.

Value of three-dimensional speckle tracking echocardiography to assess left ventricular function in hyperuricemia patients.

PubMed

Zhang, Xiaojie; Lu, Qing; Zhang, Zhuojun; Chen, Yongle; Wang, Yanan; Wang, Youngshi; Li, Zheng; Jiang, Lindi

2018-05-22

To assess the value of three-dimensional speckle tracking echocardiography (3D STE) in evaluating the left ventricular (LV) function in hyperuricemia patients. We enrolled 15 healthy controls and 40 hyperuricemia patients and collected and analyzed full-volume 3D STE images of the left ventricle in the apical four-chamber heart view. Laboratory tests and 3D STE parameters, including left ventricular ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume, stroke volume (SV), global longitudinal strain (GLS), and global circumferential strain (GCS), were compared between hyperuricemia patients and healthy controls. Hyperuricemia patients exhibited higher body mass index (24.70 ± 2.9 vs. 21.83 ± 2.4 kg/m 2 , p = 0.001), C-reactive protein (5.82 ± 9.4 vs. 1.12 ± 1.8 g/L, p = 0.012), alanine transaminase (34.26 ± 26.6 vs. 17.60 ± 13.0 U/L, p = 0.011), aspartate transaminase (24.90 ± 11.3 vs. 17.70 ± 4.1 U/L, p = 0.001), blood urea nitrogen (5.11 ± 1.6 vs. 4.18 ± 0.6 mmol/L, p = 0.046), and serum creatinine (90.25 ± 14.6 vs. 77.93 ± 10.8 μmol/L, p = 0.006) levels, as well as a lower estimated glomerular filtration rate (87.87 ± 16.5 vs. 103.64 ± 11.3 mL/min/1.73m 2 , p = 0.002). The 3D STE parameters reflecting LV function, including SV (54.71 ± 9.6 vs. 61.92 ± 14.4 mL, p = 0.024), GLS (- 20.51 ± 4.0 vs. - 23.20 ± 4.0%, p = 0.019), and GCS (- 31.30 ± 5.0 vs. - 35.65 ± 2.5%, p = 0.000), were significantly decreased in hyperuricemia patients. Furthermore, GCS was significantly correlated with the serum uric acid (sUA) level even after adjustment of confounding variables like age, body mass index, and serum creatinine. 3D STE is a novel technique for recognizing the early decline in LV function, with GLS and GCS serving as reliable indicators, in hyperuricemia patients. Moreover, the degree of decline in LV function may be correlated with the sUA level in hyperuricemia patients.

Developing Cyberspace Data Understanding: Using CRISP-DM for Host-based IDS Feature Mining

DTIC Science & Technology

2010-03-01

Developing Cyberspace Data Understanding: Using CRISP - DM for Host-based IDS Feature Mining THESIS Joseph R. Erskine, Captain, USAF AFIT/GCS/ENG/10-01...Air Force, Department of Defense, or the United States Government. AFIT/GCS/ENG/10-01 Developing Cyberspace Data Understanding: Using CRISP - DM for...Developing Cyberspace Data Understanding: Using CRISP - DM for Host-based IDS Feature Mining Joseph R. Erskine, B.S.C.S. Captain, USAF Approved: /signed/ 12

A Graphics Environment Supporting the Rapid Prototyping of Pictorial Cockpit Displays

DTIC Science & Technology

1986-12-01

0 - niDi cO 3 FIL .OF I A GRAPHICS ENVIRONMENT SUPPORTING THE RAPID PROTOTYPING OF PICTORIAL COCKPIT DISPLAYS THESIS Alan J. Braaten Captain, USAF...COCKPIT DISPLAYS THESIS Alan J. Braaten Captain, USAF AFIT/GCS/IA/86D- 1 Appram:ed for public release; distribution unlimited AFIT/GCS/MA/80- 1 A...GRAPHICS ENVIROWNT SUPPORTING THE RAPID PROTOTYPING OF PICTORIAL COCKPIT DISPLAYS THESIS Preented to the Faculty Of the School of Engineering of the Air

Poisoning severity score, APACHE II and GCS: effective clinical indices for estimating severity and predicting outcome of acute organophosphorus and carbamate poisoning.

PubMed

Sam, Kishore Gnana; Kondabolu, Krishnakanth; Pati, Dipanwita; Kamath, Asha; Pradeep Kumar, G; Rao, Padma G M

2009-07-01

Self-poisoning with organophosphorus (OP) compounds is a major cause of morbidity and mortality across South Asian countries. To develop uniform and effective management guidelines, the severity of acute OP poisoning should be assessed through scientific methods and a clinical database should be maintained. A prospective descriptive survey was carried out to assess the utility of severity scales in predicting the outcome of 71 organophosphate (OP) and carbamate poisoning patients admitted during a one year period at the Kasturba Hospital, Manipal, India. The Glasgow coma scale (GCS) scores, acute physiology and chronic health evaluation II (APACHE II) scores, predicted mortality rate (PMR) and Poisoning severity score (PSS) were estimated within 24h of admission. Significant correlation (P<0.05) between PSS and GCS and APACHE II and PMR scores were observed with the PSS scores predicting mortality significantly (P< or =0.001). A total of 84.5% patients improved after treatment while 8.5% of the patients were discharged with severe morbidity. The mortality rate was 7.0%. Suicidal poisoning was observed to be the major cause (80.2%), while other reasons attributed were occupational (9.1%), accidental (6.6%), homicidal (1.6%) and unknown (2.5%) reasons. This study highlights the application of clinical indices like GCS, APACHE, PMR and severity scores in predicting mortality and may be considered for planning standard treatment guidelines.

Transient expression of progesterone receptor and cathepsin-l in human granulosa cells during the periovulatory period.

PubMed

García, Víctor; Kohen, Paulina; Maldonado, Carola; Sierralta, Walter; Muñoz, Alex; Villarroel, Claudio; Strauss, Jerome F; Devoto, Luigi

2012-03-01

To study in vivo the progesterone receptor (PR) expression levels in human granulosa cells (GCs) during the periovulatory period and the affect of the protein kinase A (PKA) pathway on PR expression and cathepsin-L expression-activation. Experimental study. University research unit. Twenty-five women of reproductive age. Follicular fluid and GCs obtained from spontaneous cycles before and during the normal luteinizing hormone surge, and samples obtained 36 hours after human chorionic gonadotropin (hCG) administration in patients undergoing in vitro fertilization. To determine PR, cathepsin-L messenger RNA (mRNA) analysis via real-time polymerase chain reaction, and protein of PR, cathepsin-L, and PKA in human GCs. The Western blot analysis revealed that bands of PR (isoform A) were the most abundant and that mRNA (PR-A and PR-B) have a temporal pattern of expression throughout the periovulatory period. The protein levels of PR and cathepsin-L were up-regulated by hCG. The abundance of PR was diminished in the presence of PKA inhibitor, and cathepsin-L with PR receptor antagonist. The transient expression of PR in human GCs of the preovulatory follicle suggests that PR and its ligand play a role in the activation of cathepsin-L, which is presumably involved in the degradation of the follicular extracellular matrix during human ovulation. Copyright © 2012 American Society for Reproductive Medicine. All rights reserved.

Age as a major factor in the onset of multiple populations in stellar clusters

NASA Astrophysics Data System (ADS)

Martocchia, S.; Cabrera-Ziri, I.; Lardo, C.; Dalessandro, E.; Bastian, N.; Kozhurina-Platais, V.; Usher, C.; Niederhofer, F.; Cordero, M.; Geisler, D.; Hollyhead, K.; Kacharov, N.; Larsen, S.; Li, C.; Mackey, D.; Hilker, M.; Mucciarelli, A.; Platais, I.; Salaris, M.

2018-01-01

It is now well established that globular clusters (GCs) exhibit star-to-star light-element abundance variations (known as multiple populations, MPs). Such chemical anomalies have been found in (nearly) all the ancient GCs (more than 10 Gyr old) of our Galaxy and its close companions, but so far no model for the origin of MPs is able to reproduce all the relevant observations. To gain new insights into this phenomenon, we have undertaken a photometric Hubble Space Telescope survey to study clusters with masses comparable to that of old GCs, where MPs have been identified, but with significantly younger ages. Nine clusters in the Magellanic Clouds with ages between ∼1.5 and 11 Gyr have been targeted in this survey. We confirm the presence of MPs in all clusters older than 6 Gyr and we add NGC 1978 to the group of clusters for which MPs have been identified. With an age of ∼2 Gyr, NGC 1978 is the youngest cluster known to host chemical abundance spreads found to date. We do not detect evident star-to-star variations for slightly younger massive clusters (∼1.7 Gyr), thus pointing towards an unexpected age dependence for the onset of MPs. This discovery suggests that the formation of MPs is not restricted to the early Universe and that GCs and young massive clusters share common formation and evolutionary processes.

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

Lim, Dongwook; Han, Sang-Il; Lee, Young-Wook

There is increasing evidence for the presence of multiple red giant branches (RGBs) in the color-magnitude diagrams of massive globular clusters (GCs). In order to investigate the origin of this split on the RGB, we have performed new narrow-band Ca photometry and low-resolution spectroscopy for M22, NGC 1851, and NGC 288. We find significant differences (more than 4σ) in calcium abundance from the spectroscopic HK' index for M22 and NGC 1851. We also find more than 8σ differences in CN-band strength between the Ca-strong and Ca-weak subpopulations for these GCs. For NGC 288, however, a large difference is detected onlymore » in the CN strength. The calcium abundances of RGB stars in this GC are identical to within the errors. This is consistent with the conclusion from our new Ca photometry where the RGB splits are confirmed in M22 and NGC 1851, but not in NGC 288. We also find interesting differences in the CN-CH correlations among these GCs. While CN and CH are anti-correlated in NGC 288, they show a positive correlation in M22. NGC 1851, however, shows no difference in CH between the two groups of stars with different CN strengths. We suggest that all of these systematic differences would be best explained by how strongly Type II supernovae enrichment has contributed to the chemical evolution of these GCs.« less

Globular clusters and environmental effects in galaxy clusters

NASA Astrophysics Data System (ADS)

Sales, Laura

2016-10-01

Globular clusters are old compact stellar systems orbiting around galaxies of all types. Tens of thousands of them can also be found populating the intra-cluster regions of nearby galaxy clusters like Virgo and Coma. Thanks to the HST Frontier Fields program, GCs are starting now to be detected also in intermediate redshift clusters. Yet, despite their ubiquity, a theoretical model for the formation and evolution of GCs is still missing, especially within the cosmological context.Here we propose to use cosmological hydrodynamical simulations of 18 galaxy clusters coupled to a post-processing GC formation model to explore the assembly of galaxies in clusters together with their expected GC population. The method, which has already been implemented and tested, will allow us to characterize for the first time the number, radial distribution and kinematics of GCs in clusters, with products directly comparable to observational maps. We will explore cluster-to-cluster variations and also characterize the build up of the intra-cluster component of GCs with time.As the method relies on a detailed study of the star-formation history of galaxies, we will jointly constrain the predicted quenching time-scales for satellites and the occurrence of starburst events associated to infall and orbital pericenters of galaxies in massive clusters. This will inform further studies on the distribution, velocity and properties of post-starburst galaxies in past, ongoing and future HST programs.

Traumatic brain injury: It is all about definition.

PubMed

Savitsky, B; Givon, A; Rozenfeld, M; Radomislensky, I; Peleg, K

2016-01-01

TBI may be defined by different methods. Some may be most useful for immediate clinical purposes, however less optimal for epidemiologic research. Other methods, such as the Abbreviated Injury Score (AIS), may prove more beneficial for this task, if the cut-off-points for their categories are defined correctly. To reveal the optimal cut-off-points for AIS in definition of severity of TBI in order to ensure uniformity between future studies of TBI. Mortality of patients with TBI AIS 3, 4 was 1.9% and 2.9% respectively, comparing with 31.1% among TBI AIS 5+. Predictive discrimination ability of the model with cut-off-points of 5+ for TBI AIS (in comparison with other cut-off-points) was better. Patients with missing Glasgow Coma Scale (GCS) in the ED had an in-hospital mortality rate of 11.5%. In this group, 25% had critical TBI according to AIS. Normal GCS didn't indicate an absence of head injury, as, among patients with GCS 15 in the ED, 26% had serious/critical TBI injury. Moreover, 7% of patients with multiple injury and GCS 3-8 had another reason than head injury for unconsciousness. This study recommends the adoption of an AIS cut-off ≥ 5 as a valid definition of severe TBI in epidemiological studies, while AIS 3-4 may be defined as 'moderate' TBI and AIS 1-2 as 'mild'.

Expression of glucocorticoid receptor isoforms and associations with serine/arginine-rich protein 30c and 40 in patients with systemic lupus erythematosus.

PubMed

Guan, Yan-Chun; Jiang, Lei; Ma, Liang-Liang; Sun, Xiang-Nan; Yu, Dan-Dan; Liu, Jing; Qu, Dong-Xia; Fang, Mei-Yun

2015-01-01

To investigate the expression of glucocorticoid receptor (GR) isoforms in patients with systemic lupus erythematosus (SLE), confirm the main GR isoforms involving in glucocorticoids (GC) resistance, and explore the associations of GR isoforms with serine/arginine-rich protein (SRp) 30c and SRp40. Seventy patients with SLE and thirty-eight age- and sex-matched controls were recruited. All patients received prednisone (0.5-1 mg/kg/d) as their routine therapy. According to the therapeutic effect, patients were divided into glucocorticoid-resistant (GCR) and glucocorticoid-sensitive (GCS) groups. Transcript levels of GRα, GRβ, GRγ, GR-P, SRp30c and SRp40 in peripheral blood mononuclear cells (PBMCs) were determined by real-time PCR. GRα and GRβ proteins were detected by western blotting. Trial registration number is ChiCTR-RCH-12002808. Four GR transcripts in SLE patients showed the following trend: GRα (51.85%) > GR-P (23.78%) > GRγ (13.08%) >GRβ (0.03%). GR-P transcript and ratio of GRα/GR-P in SLE patients were significantly higher than that in controls (p<0.05). GRα transcript and protein as well as SRp40 transcript in GCS group were significantly higher than that in the GCR group before GC treatment (p<0.05). In the GCS group, GRα transcript and SRp40 transcript were significantly higher after GC treatment than that before GC treatment (p<0.05). In the GCR group, GR-P transcript was significantly higher after GC treatment than that before GC treatment (p<0.05). Positive correlation between SRp40 and GRα transcript was found (p<0.05). Additionally, SLE Disease Activity Index scores were significantly negatively correlated with GRα transcript and protein expression (p<0.05). Our data demonstrated that the decreased expression of GRα might be the evidence of high disease activity and help to predict GC resistance. GR-P isoform might be implicated in the development of resistance. Additionally, the preliminary finding suggested that SRp40 might be associated with GRα transcripts in SLE patients.

The Head Injury Retrieval Trial (HIRT): a single-centre randomised controlled trial of physician prehospital management of severe blunt head injury compared with management by paramedics only

PubMed Central

Garner, Alan A; Mann, Kristy P; Fearnside, Michael; Poynter, Elwyn; Gebski, Val

2015-01-01

Background Advanced prehospital interventions for severe brain injury remains controversial. No previous randomised trial has been conducted to evaluate additional physician intervention compared with paramedic only care. Methods Participants in this prospective, randomised controlled trial were adult patients with blunt trauma with either a scene GCS score <9 (original definition), or GCS<13 and an Abbreviated Injury Scale score for the head region ≥3 (modified definition). Patients were randomised to either standard ground paramedic treatment or standard treatment plus a physician arriving by helicopter. Patients were evaluated by 30-day mortality and 6-month Glasgow Outcome Scale (GOS) scores. Due to high non-compliance rates, both intention-to-treat and as-treated analyses were preplanned. Results 375 patients met the original definition, of which 197 was allocated to physician care. Differences in the 6-month GOS scores were not significant on intention-to-treat analysis (OR 1.11, 95% CI 0.74 to 1.66, p=0.62) nor was the 30-day mortality (OR 0.91, 95% CI 0.60 to 1.38, p=0.66). As-treated analysis showed a 16% reduction in 30-day mortality in those receiving additional physician care; 60/195 (29%) versus 81/180 (45%), p<0.01, Number needed to treat =6. 338 patients met the modified definition, of which 182 were allocated to physician care. The 6-month GOS scores were not significantly different on intention-to-treat analysis (OR 1.14, 95% CI 0.73 to 1.75, p=0.56) nor was the 30-day mortality (OR 1.05, 95% CI 0.66 to 1.66, p=0.84). As-treated analyses were also not significantly different. Conclusions This trial suggests a potential mortality reduction in patients with blunt trauma with GCS<9 receiving additional physician care (original definition only). Confirmatory studies which also address non-compliance issues are needed. Trial registration number NCT00112398. PMID:25795741

The Influence of Ectopic Migration of Granule Cells into the Hilus on Dentate Gyrus-CA3 Function

PubMed Central

Myers, Catherine E.; Bermudez-Hernandez, Keria; Scharfman, Helen E.

2013-01-01

Postnatal neurogenesis of granule cells (GCs) in the dentate gyrus (DG) produces GCs that normally migrate from the subgranular zone to the GC layer. However, GCs can mismigrate into the hilus, the opposite direction. Previous descriptions of these hilar ectopic GCs (hEGCs) suggest that they are rare unless there are severe seizures. However, it is not clear if severe seizures are required, and it also is unclear if severe seizures are responsible for the abnormalities of hEGCs, which include atypical dendrites and electrophysiological properties. Here we show that large numbers of hEGCs develop in a transgenic mouse without severe seizures. The mice have a deletion of BAX, which normally regulates apoptosis. Surprisingly, we show that hEGCs in the BAX-/- mouse have similar abnormalities as hEGCs that arise after severe seizures. We next asked if there are selective effects of hEGCs, i.e., whether a robust population of hEGCs would have any effect on the DG if they were induced without severe seizures. Indeed, this appears to be true, because it has been reported that BAX-/- mice have defects in a behavior that tests pattern separation, which depends on the DG. However, inferring functional effects of hEGCs is difficult in mice with a constitutive BAX deletion because there is decreased apoptosis in and outside the DG. Therefore, a computational model of the normal DG and hippocampal subfield CA3 was used. Adding a small population of hEGCs (5% of all GCs), with characteristics defined empirically, was sufficient to disrupt a simulation of pattern separation and completion. Modeling results also showed that effects of hEGCs were due primarily to “backprojections” of CA3 pyramidal cell axons to the hilus. The results suggest that hEGCs can develop for diverse reasons, do not depend on severe seizures, and a small population of hEGCs may impair DG-dependent function. PMID:23840835

The peculiar Na-O anticorrelation of the bulge globular cluster NGC 6440

NASA Astrophysics Data System (ADS)

Muñoz, C.; Villanova, S.; Geisler, D.; Saviane, I.; Dias, B.; Cohen, R. E.; Mauro, F.

2017-08-01

Context. Galactic globular clusters (GCs) are essential tools for understanding the earliest epoch of the Milky Way, since they are among the oldest objects in the Universe and can be used to trace its formation and evolution. Current studies using high-resolution spectroscopy for many stars in each of a large sample of GCs allow us to develop a detailed observational picture of their formation and their relation with the Galaxy. However, it is necessary to complete this picture by including GCs that belong to all major Galactic components, including the bulge. Aims: Our aim is to perform a detailed chemical analysis of the bulge GC NGC 6440 in order to determine if this object has multiple populations (MPs) and investigate its relation with the bulge of the Milky Way and with the other Galactic GCs, especially those associated with the bulge, which are largely poorly studied. Methods: We determined the stellar parameters and the chemical abundances of light elements (Na, Al), iron-peak elements (Fe, Sc, Mn, Co, Ni), α-elements (O, Mg, Si, Ca, Ti) and heavy elements (Ba, Eu) in seven red giant members of NGC 6440 using high-resolution spectroscopy from FLAMES-UVES. Results: We found a mean iron content of [Fe/H] =-0.50 ± 0.03 dex in agreement with other studies. We found no internal iron spread. On the other hand, Na and Al show a significant intrinsic spread, but the cluster has no significant O-Na anticorrelation nor does it exhibit a Mg-Al anticorrelation. The α-elements show good agreement with the bulge field star trend, although they are at the high alpha end and are also higher than those of other GCs of comparable metallicity. The heavy elements are dominated by the r-process, indicating a strong contribution by SNeII. The chemical analysis suggests an origin similar to that of the bulge field stars.

Eosinophil Resistance to Glucocorticoid-Induced Apoptosis is Mediated by the Transcription Factor NFIL3

PubMed Central

Pazdrak, Konrad; Moon, Young; Straub, Christof; Stafford, Susan; Kurosky, Alexander

2016-01-01

The mainstay of asthma therapy, glucocorticoids (GCs) exert their therapeutic effects through the inhibition of inflammatory signaling and induction of eosinophil apoptosis. However, laboratory and clinical observations of GC-resistant asthma suggest that GCs' effects on eosinophil viability may depend on the state of eosinophil activation. In the present study we demonstrate that eosinophils stimulated with IL-5 show impaired prop-aptoptotic response to GCs. We sought to determine the contribution of GC-mediated transactivating (TA) and transrepressing (TR) pathways in modulation of activated eosinophils' response to GC by comparing their response to the selective GC receptor (GR) agonist Compound A (CpdA) devoid of TA activity to that upon treatment with Dexamethasone (Dex). IL-5-activated eosinophils showed contrasting responses to CpdA and Dex, as IL-5-treated eosinophils showed no increase in apoptosis compared to cells treated with Dex alone, while CpdA elicited an apoptotic response regardless of IL-5 stimulation. Proteomic analysis revealed that both Nuclear Factor IL-3 (NFIL3) and Map Kinase Phosphatase 1 (MKP1) were inducible by IL-5 and enhanced by Dex; however, CpdA had no effect on NFIL3 and MKP1 expression. We found that inhibiting NFIL3 with specific siRNA or by blocking the IL-5-inducible Pim-1 kinase abrogated the protective effect of IL-5 on Dex-induced apoptosis, indicating crosstalk between IL-5 anti-apoptotic pathways and GR-mediated TA signaling occurring via the NFIL3 molecule. Collectively, these results indicate that 1) GCs' TA pathway may support eosinophil viability in IL-5-stimulated cells through synergistic upregulation of NFIL3; and 2) functional inhibition of IL-5 signaling (anti-Pim1) or the use of selective GR agonists that don't upregulate NFIL3 may be effective strategies for the restoring pro-apoptotic effect of GCs on IL-5-activated eosinophils. PMID:26880402

Morphine Modulates Adult Neurogenesis and Contextual Memory by Impeding the Maturation of Neural Progenitors.

PubMed

Zhang, Yue; Xu, Chi; Zheng, Hui; Loh, Horace H; Law, Ping-Yee

2016-01-01

The regulation of adult neurogenesis by opiates has been implicated in modulating different addiction cycles. At which neurogenesis stage opiates exert their action remains unresolved. We attempt to define the temporal window of morphine's inhibition effect on adult neurogenesis by using the POMC-EGFP mouse model, in which newborn granular cells (GCs) can be visualized between days 3-28 post-mitotic. The POMC-EGFP mice were trained under the 3-chambers conditioned place preference (CPP) paradigm with either saline or morphine. We observed after 4 days of CPP training with saline, the number of EGFP-labeled newborn GCs in sub-granular zone (SGZ) hippocampus significantly increased compared to mice injected with saline in their homecage. CPP training with morphine significantly decreased the number of EGFP-labeled GCs, whereas no significant difference in the number of EGFP-labeled GCs was observed with the homecage mice injected with the same dose of morphine. Using cell-type selective markers, we observed that morphine reduced the number of late stage progenitors and immature neurons such as Doublecortin (DCX) and βIII Tubulin (TuJ1) positive cells in the SGZ but did not reduce the number of early progenitors such as Nestin, SOX2, or neurogenic differentiation-1 (NeuroD1) positive cells. Analysis of co-localization between different cell markers shows that morphine reduced the number of adult-born GCs by interfering with differentiation of early progenitors, but not by inducing apoptosis. In addition, when NeuroD1 was over-expressed in DG by stereotaxic injection of lentivirus, it rescued the loss of immature neurons and prolonged the extinction of morphine-trained CPP. These results suggest that under the condition of CPP training paradigm, morphine affects the transition of neural progenitor/stem cells to immature neurons via a mechanism involving NeuroD1.

Photometric and kinematic studies of extragalactic globular cluster systems

NASA Astrophysics Data System (ADS)

Dowell, Jessica

Globular clusters (GCs) are old, luminous, compact collections of stars found in galaxy halos that formed during the early stages of galaxy formation. Because of this, GCs serve as excellent tracers of the formation, structure, and merger history of their host galaxies. My dissertation will examine both the photometric and kinematic properties of GC systems and their relationship to their host galaxies. In the first section, I will present the analysis of the GC systems of two spiral galaxies, NGC 891 and NGC 1055. I will discuss the photometric methods used to detect GCs using wide-field BVR imaging and to quantify the global properties of the system such as the total number of GCs and their radial distribution. My results for these two GC systems were compared to those of other galaxies. I will also present the results of spectroscopic follow-up for two giant galaxies: the S0 galaxy NGC 4594 (M104), and the elliptical galaxy NGC 3379 (M105). I measured the radial velocities of GCs in these two galaxies, and combined them with published results to determine the mass distribution and mass-to-light (M/L) ratio profile for each galaxy out to large effective radius (7-9 Re). For both galaxies, I found that the M/L profiles increase with radius and do not flatten, which suggests that the dark matter halos in these galaxies extend to the edge of my data. I also looked for evidence of rotation in the GC systems, and found that neither system exhibits significant rotation around the host galaxy. I examined the velocity dispersion profile of each GC system and found kinematic differences between the red and blue GC subpopulations. Finally, I compared my results to mass estimates for these galaxies from other kinematic tracers and considered them in the context of galaxy formation models.

Employing individual measures of baseline glucocorticoids as population-level conservation biomarkers: considering within-individual variation in a breeding passerine

PubMed Central

Madliger, Christine L; Love, Oliver P

2016-01-01

Abstract Labile physiological variables, such as stress hormones [i.e. glucocorticoids (GCs)], allow individuals to react to perturbations in their environment and may therefore reflect the effect of disturbances or positive conservation initiatives in advance of population-level demographic measures. Although the application of GCs as conservation biomarkers has been of extensive interest, few studies have explicitly investigated whether baseline GC concentrations respond to disturbances consistently across individuals. However, confirmation of consistent responses is of paramount importance to assessing the ease of use of GCs in natural systems and to making valid interpretations regarding population-level change (or lack of change) in GC concentrations. We investigated whether free-ranging female tree swallows (Tachycineta bicolor) display individually specific changes in baseline glucocorticoid concentrations naturally over the breeding season (from incubation to offspring provisioning) and in response to a manipulation of foraging profitability (representing a decrease in access to food resources). We show that baseline GC concentrations are repeatable within individuals over reproduction in natural conditions. However, in response to a reduction in foraging ability, baseline GC concentrations increase at the population level but are not repeatable within individuals, indicating a high level of within-individual variation. Overall, we suggest that baseline GCs measured on a subset of individuals may not provide a representative indication of responses to environmental change at the population level, and multiple within-individual measures may be necessary to determine the fitness correlates of GC concentrations. Further validation should be completed across a variety of taxa and life-history stages. Moving beyond a traditional cross-sectional approach by incorporating repeated-measures methods will be necessary to assess the suitability of baseline GCs as biomarkers of environmental change and population persistence, particularly from a logistical and ease-of-use perspective for conservation managers. PMID:27757239

Transactivation of micrornA-320 by microRNA-383 regulates granulosa cell functions by targeting E2F1 and SF-1 proteins.

PubMed

Yin, Mianmian; Wang, Xiaorong; Yao, Guidong; Lü, Mingrong; Liang, Meng; Sun, Yingpu; Sun, Fei

2014-06-27

Our previous studies have shown that microRNA-320 (miR-320) is one of the most down-regulated microRNAs (miRNA) in mouse ovarian granulosa cells (GCs) after TGF-β1 treatment. However, the underlying mechanisms of miR-320 involved in GC function during follicular development remain unknown. In this study, we found that pregnant mare serum gonadotropin treatment resulted in the suppression of miR-320 expression in a time-dependent manner. miR-320 was mainly expressed in GCs and oocytes of mouse ovarian follicles in follicular development. Overexpression of miR-320 inhibited estradiol synthesis and proliferation of GCs through targeting E2F1 and SF-1. E2F1/SF-1 mediated miR-320-induced suppression of GC proliferation and of GC steroidogenesis. FSH down-regulated the expression of miR-320 and regulated the function of miR-320 in mouse GCs. miR-383 promoted the expression of miR-320 and enhanced miR-320-mediated suppression of GC proliferation. Injection of miR-320 into the ovaries of mice partially promoted the production of testosterone and progesterone but inhibited estradiol release in vivo. Moreover, the expression of miR-320 and miR-383 was up-regulated in the follicular fluid of polycystic ovarian syndrome patients, although the expression of E2F1 and SF-1 was down-regulated in GCs. These data demonstrated that miR-320 regulates the proliferation and steroid production by targeting E2F1 and SF-1 in the follicular development. Understanding the regulation of miRNA biogenesis and function in the follicular development will potentiate the usefulness of miRNA in the treatment of reproduction and some steroid-related disorders. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

An Intuitive Graphical User Interface for Small UAS

DTIC Science & Technology

2013-05-01

reduced from two to one . The stock displays, including video with text overlay on one and FalconView on the other, are replaced with a single, graphics...INTRODUCTION Tactical UAVs such as the Raven, Puma and Wasp are often used by dismounted warfighters on missions that require a high degree of mobility by...the operators on the ground. The current ground control stations (GCS) for the Wasp, Raven and Puma tactical UAVs require two people and two user

Using Causal Models to Manage the Cyber Threat to C2 Agility: Working with the Benefit of Hindsight

DTIC Science & Technology

2014-06-01

comprising event types that begin with access to the Ground Control Station network (‘Reconnaissance’), carry out persona management activities leading to...occurring. Figure 9 shows a chain where ‘GCS Hostile Persona Management’ has been detected, leading to a heightened assessment of the probability of...evidence occurs of hostile persona management that calls into question the integrity of the mission itself. What now: search for a mitigation, assess

Enhancement of Identity in the Hydraulic Characteristics of a Gas Centrifuge for Isotope Separation

NASA Astrophysics Data System (ADS)

Yatsenko, D. V.; Borisevich, V. D.; Godisov, O. N.

The problem of non-identity in characteristics of the GCs for uranium isotope separation grows up with increase of a rotor speed of rotation. It may lead to noticeable decrease of the separative power of the centrifugal machines. The carried out assessments allowed to get the dependence of the relative separation performance losses on the non-identity in the hydraulic characteristics of the GCs connected in parallel. The results of calculation are compared with that of obtained in experiments.

Prehospital Heart Rate and Blood Pressure Increase the Positive Predictive Value of the Glasgow Coma Scale for High-Mortality Traumatic Brain Injury

DTIC Science & Technology

2014-05-15

TBI versus those with abnormalities in GCS alone. This could be useful for mobilizing resources (e.g., neurosurgeons and operating rooms at the...have high-mortality TBI versus those with abnormalities in GCS alone. This could be useful for mobilizing resources (e.g., neurosurgeons and... neurosurgeon at the earliest juncture. Third, improved risk stratification could be used to develop more rational clinical de- cision-making algorithms for

Understanding the Importance and Practice of Credible Leadership at Program Executive Office Ground Combat Systems (PEO GCS) and Program Executive Office Combat Support and Combat Service Support (PEO CS and CSS)

DTIC Science & Technology

2017-03-30

and Program Executive Office Combat Support and Combat Service Support (PEO CS&CSS) Chad P. Stocker March 30, 2017 Submitted to...to Defense Acquisition University in partial fulfillment of the requirement of the Senior Service College Fellowship CREDIBLE LEADERSHIP AT PEO...of Credible Leadership at Program Executive Office Ground Combat Systems (PEO GCS) and Program Executive Office Combat Support and Combat Service