Functional connectivity-based parcellation and connectome of cortical midline structures in the mouse: a perfusion autoradiography study.

PubMed

Holschneider, Daniel P; Wang, Zhuo; Pang, Raina D

2014-01-01

Rodent cortical midline structures (CMS) are involved in emotional, cognitive and attentional processes. Tract tracing has revealed complex patterns of structural connectivity demonstrating connectivity-based integration and segregation for the prelimbic, cingulate area 1, retrosplenial dysgranular cortices dorsally, and infralimbic, cingulate area 2, and retrosplenial granular cortices ventrally. Understanding of CMS functional connectivity (FC) remains more limited. Here we present the first subregion-level FC analysis of the mouse CMS, and assess whether fear results in state-dependent FC changes analogous to what has been reported in humans. Brain mapping using [(14)C]-iodoantipyrine was performed in mice during auditory-cued fear conditioned recall and in controls. Regional cerebral blood flow (CBF) was analyzed in 3-D images reconstructed from brain autoradiographs. Regions-of-interest were selected along the CMS anterior-posterior and dorsal-ventral axes. In controls, pairwise correlation and graph theoretical analyses showed strong FC within each CMS structure, strong FC along the dorsal-ventral axis, with segregation of anterior from posterior structures. Seed correlation showed FC of anterior regions to limbic/paralimbic areas, and FC of posterior regions to sensory areas-findings consistent with functional segregation noted in humans. Fear recall increased FC between the cingulate and retrosplenial cortices, but decreased FC between dorsal and ventral structures. In agreement with reports in humans, fear recall broadened FC of anterior structures to the amygdala and to somatosensory areas, suggesting integration and processing of both limbic and sensory information. Organizational principles learned from animal models at the mesoscopic level (brain regions and pathways) will not only critically inform future work at the microscopic (single neurons and synapses) level, but also have translational value to advance our understanding of human brain architecture.

Human adipose tissue from normal and tumoral breast regulates the behavior of mammary epithelial cells.

PubMed

Pistone Creydt, Virginia; Fletcher, Sabrina Johanna; Giudice, Jimena; Bruzzone, Ariana; Chasseing, Norma Alejandra; Gonzalez, Eduardo Gustavo; Sacca, Paula Alejandra; Calvo, Juan Carlos

2013-02-01

Stromal-epithelial interactions mediate both breast development and breast cancer progression. In the present work, we evaluated the effects of conditioned media (CMs) of human adipose tissue explants from normal (hATN) and tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases activity on tumor (MCF-7 and IBH-7) and non-tumor (MCF-10A) human breast epithelial cell lines. Human adipose tissues were obtained from patients and the conditioned medium from hATN and hATT collected after 24 h of incubation. MCF-10A, MCF-7 and IBH-7 cells were grown and incubated with CMs and proliferation and adhesion, as well as migration ability and metalloprotease activity, of epithelial cells after exposing cell cultures to hATN- or hATT-CMs were quantified. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post hoc tests were performed. Tumor and non-tumor breast epithelial cells significantly increased their proliferation activity after 24 h of treatment with hATT-CMs compared to control-CMs. Furthermore, cellular adhesion of these two tumor cell lines was significantly lower with hATT-CMs than with hATN-CMs. Therefore, hATT-CMs seem to induce significantly lower expression or less activity of the components involved in cellular adhesion than hATN-CMs. In addition, hATT-CMs induced pro-MMP-9 and MMP-9 activity and increased the migration of MCF-7 and IBH-7 cells compared to hATN-CMs. We conclude that the microenvironment of the tumor interacts in a dynamic way with the mutated epithelium. This evidence leads to the possibility to modify the tumor behavior/phenotype through the regulation or modification of its microenvironment. We developed a model in which we obtained CMs from adipose tissue explants completely, either from normal or tumor breast. In this way, we studied the contribution of soluble factors independently of the possible effects of direct cell contact.

Assessment of Biases Against Latinos and African Americans Among Primary Care Providers and Community Members

PubMed Central

Havranek, Edward P.; Price, David W.; Hanratty, Rebecca; Fairclough, Diane L.; Farley, Tillman; Hirsh, Holen K.; Steiner, John F.

2013-01-01

Objectives. We assessed implicit and explicit bias against both Latinos and African Americans among experienced primary care providers (PCPs) and community members (CMs) in the same geographic area. Methods. Two hundred ten PCPs and 190 CMs from 3 health care organizations in the Denver, Colorado, metropolitan area completed Implicit Association Tests and self-report measures of implicit and explicit bias, respectively. Results. With a 60% participation rate, the PCPs demonstrated substantial implicit bias against both Latinos and African Americans, but this was no different from CMs. Explicit bias was largely absent in both groups. Adjustment for background characteristics showed the PCPs had slightly weaker ethnic/racial bias than CMs. Conclusions. This research provided the first evidence of implicit bias against Latinos in health care, as well as confirming previous findings of implicit bias against African Americans. Lack of substantive differences in bias between the experienced PCPs and CMs suggested a wider societal problem. At the same time, the wide range of implicit bias suggested that bias in health care is neither uniform nor inevitable, and important lessons might be learned from providers who do not exhibit bias. PMID:23153155

Concise Review: Criteria for Chamber‐Specific Categorization of Human Cardiac Myocytes Derived from Pluripotent Stem Cells

PubMed Central

Kane, Christopher

2017-01-01

Abstract Human pluripotent stem cell‐derived cardiomyocytes (PSC‐CMs) have great potential application in almost all areas of cardiovascular research. A current major goal of the field is to build on the past success of differentiation strategies to produce CMs with the properties of those originating from the different chambers of the adult human heart. With no anatomical origin or developmental pathway to draw on, the question of how to judge the success of such approaches and assess the chamber specificity of PSC‐CMs has become increasingly important; commonly used methods have substantial limitations and are based on limited evidence to form such an assessment. In this article, we discuss the need for chamber‐specific PSC‐CMs in a number of areas as well as current approaches used to assess these cells on their likeness to those from different chambers of the heart. Furthermore, describing in detail the structural and functional features that distinguish the different chamber‐specific human adult cardiac myocytes, we propose an evidence‐based tool to aid investigators in the phenotypic characterization of differentiated PSC‐CMs. Stem Cells 2017;35:1881–1897 PMID:28577296

Enantioselectively controlled release of chiral drug (metoprolol) using chiral mesoporous silica materials

NASA Astrophysics Data System (ADS)

Guo, Zhen; Du, Yu; Liu, Xianbin; Ng, Siu-Choon; Chen, Yuan; Yang, Yanhui

2010-04-01

Chiral porous materials have attracted burgeoning attention on account of their potential applications in many areas, such as enantioseparation, chiral catalysis, chemical sensors and drug delivery. In this report, chiral mesoporous silica (CMS) materials with various pore sizes and structures were prepared using conventional achiral templates (other than chiral surfactant) and a chiral cobalt complex as co-template. The synthesized CMS materials were characterized by x-ray diffraction, nitrogen physisorption, scanning electron microscope and transmission electron microscope. These CMS materials, as carriers, were demonstrated to be able to control the enantioselective release of a representative chiral drug (metoprolol). The release kinetics, as modeled by the power law equation, suggested that the release profiles of metoprolol were remarkably dependent on the pore diameter and pore structure of CMS materials. More importantly, R- and S-enantiomers of metoprolol exhibited different release kinetics on CMS compared to the corresponding achiral mesoporous silica (ACMS), attributable to the existence of local chirality on the pore wall surface of CMS materials. The chirality of CMS materials on a molecular level was further substantiated by vibrational circular dichroism measurements.

HCN2 channels in the ventral tegmental area regulate behavioral responses to chronic stress

PubMed Central

Zhong, Peng; Vickstrom, Casey R; Liu, Xiaojie; Hu, Ying; Yu, Laikang; Yu, Han-Gang

2018-01-01

Dopamine neurons in the ventral tegmental area (VTA) are powerful regulators of depression-related behavior. Dopamine neuron activity is altered in chronic stress-based models of depression, but the underlying mechanisms remain incompletely understood. Here, we show that mice subject to chronic mild unpredictable stress (CMS) exhibit anxiety- and depressive-like behavior, which was associated with decreased VTA dopamine neuron firing in vivo and ex vivo. Dopamine neuron firing is governed by voltage-gated ion channels, in particular hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Following CMS, HCN-mediated currents were decreased in nucleus accumbens-projecting VTA dopamine neurons. Furthermore, shRNA-mediated HCN2 knockdown in the VTA was sufficient to recapitulate CMS-induced depressive- and anxiety-like behavior in stress-naïve mice, whereas VTA HCN2 overexpression largely prevented CMS-induced behavioral deficits. Together, these results reveal a critical role for HCN2 in regulating VTA dopamine neuronal activity and depressive-related behaviors. PMID:29256865

Permeability predictions for sand-clogged Portland cement pervious concrete pavement systems.

PubMed

Haselbach, Liv M; Valavala, Srinivas; Montes, Felipe

2006-10-01

Pervious concrete is an alternative paving surface that can be used to reduce the nonpoint source pollution effects of stormwater runoff from paved surfaces such as roadways and parking lots by allowing some of the rainfall to permeate into the ground below. This infiltration rate may be adversely affected by clogging of the system, particularly clogging or covering by sand in coastal areas. A theoretical relation was developed between the effective permeability of a sand-clogged pervious concrete block, the permeability of sand, and the porosity of the unclogged block. Permeabilities were then measured for Portland cement pervious concrete systems fully covered with extra fine sand in a flume using simulated rainfalls. The experimental results correlated well with the theoretical calculated permeability of the pervious concrete system for pervious concrete systems fully covered on the surface with sand. Two different slopes (2% and 10%) were used. Rainfall rates were simulated for the combination of direct rainfall (passive runoff) and for additional stormwater runoff from adjacent areas (active runoff). A typical pervious concrete block will allow water to pass through at flow rates greater than 0.2 cm/s and a typical extra fine sand will have a permeability of approximately 0.02 cm/s. The limit of the system with complete sand coverage resulted in an effective system permeability of approximately 0.004 cm/s which is similar to the rainfall intensity of a 30 min duration, 100-year frequency event in the southeastern United States. The results obtained are important in designing and evaluating pervious concrete as a paving surface within watershed management systems for controlling the quantity of runoff.

Touch Satiety: Differential Effects of Stroking Velocity on Liking and Wanting Touch Over Repetitions

PubMed Central

Triscoli, Chantal; Ackerley, Rochelle; Sailer, Uta

2014-01-01

A slow, gentle caress of the skin is a salient hedonic stimulus. Low threshold, unmyelinated C-tactile afferents fire preferentially to this type of touch, where slow (<1 cm/s) and fast (>10 cm/s) stroking velocities produce lower firing frequencies and are rated as less pleasant. The current aim was to investigate how the experience of tactile pleasantness changes with repeated exposure (satiety to touch). A further aim was to determine whether tactile satiety varied with different stroking velocities. The experimental paradigm used a controlled brush stroke to the forearm that was delivered repeatedly for ∼50 minutes. In Experiment 1, brush strokes were administered at three different velocities (0.3 cm/s, 3 cm/s and 30 cm/s), which were presented in a pseudo-randomised order. In Experiment 2, brush strokes were applied using only one velocity (either 3 or 30 cm/s). After each stroke, the participants rated both subjective pleasantness (liking) and wanting (the wish to be further exposed to the same stimulus) for each tactile sensation. In Experiment 1, both pleasantness and wanting showed a small, but significant, decrease over repetitions during stroking at 3 cm/s only, where the mean values for pleasantness and wanting were similar. Conversely, slower (0.3 cm/s) and faster (30 cm/s) stroking showed no decrease in ratings over time, however pleasantness was rated higher than wanting. In Experiment 2, both pleasantness and wanting showed a significant decrease over repetitions for both applied velocities, with a larger decrease in ratings for stroking at 3 cm/s. In conclusion, satiety to touch occurred with a slow onset and progression, where pleasantness and wanting ratings to stroking at 3 cm/s were affected more than at the slower or faster velocities. Tactile satiety appears to differ compared to appetitive and olfactory satiety, because the hedonic and rewarding aspects of touch persist for some time. PMID:25405620

Functional connectivity-based parcellation and connectome of cortical midline structures in the mouse: a perfusion autoradiography study

PubMed Central

Holschneider, Daniel P.; Wang, Zhuo; Pang, Raina D.

2014-01-01

Rodent cortical midline structures (CMS) are involved in emotional, cognitive and attentional processes. Tract tracing has revealed complex patterns of structural connectivity demonstrating connectivity-based integration and segregation for the prelimbic, cingulate area 1, retrosplenial dysgranular cortices dorsally, and infralimbic, cingulate area 2, and retrosplenial granular cortices ventrally. Understanding of CMS functional connectivity (FC) remains more limited. Here we present the first subregion-level FC analysis of the mouse CMS, and assess whether fear results in state-dependent FC changes analogous to what has been reported in humans. Brain mapping using [14C]-iodoantipyrine was performed in mice during auditory-cued fear conditioned recall and in controls. Regional cerebral blood flow (CBF) was analyzed in 3-D images reconstructed from brain autoradiographs. Regions-of-interest were selected along the CMS anterior-posterior and dorsal-ventral axes. In controls, pairwise correlation and graph theoretical analyses showed strong FC within each CMS structure, strong FC along the dorsal-ventral axis, with segregation of anterior from posterior structures. Seed correlation showed FC of anterior regions to limbic/paralimbic areas, and FC of posterior regions to sensory areas–findings consistent with functional segregation noted in humans. Fear recall increased FC between the cingulate and retrosplenial cortices, but decreased FC between dorsal and ventral structures. In agreement with reports in humans, fear recall broadened FC of anterior structures to the amygdala and to somatosensory areas, suggesting integration and processing of both limbic and sensory information. Organizational principles learned from animal models at the mesoscopic level (brain regions and pathways) will not only critically inform future work at the microscopic (single neurons and synapses) level, but also have translational value to advance our understanding of human brain architecture. PMID:24966831

Comparative meta-analysis and experimental kinetic investigation of column and batch bottle microcosm treatability studies informing in situ groundwater remedial design.

PubMed

Driver, Erin M; Roberts, Jeff; Dollar, Peter; Charles, Maurissa; Hurst, Paul; Halden, Rolf U

2017-02-05

A systematic comparison was performed between batch bottle and continuous-flow column microcosms (BMs and CMs, respectively) commonly used for in situ groundwater remedial design. Review of recent literature (2000-2014) showed a preference for reporting batch kinetics, even when corresponding column data were available. Additionally, CMs produced higher observed rate constants, exceeding those of BMs by a factor of 6.1±1.1 standard error. In a subsequent laboratory investigation, 12 equivalent microcosm pairs were constructed from fractured bedrock and perchloroethylene (PCE) impacted groundwater. First-order PCE transformation kinetics of CMs were 8.0±4.8 times faster than BMs (rates: 1.23±0.87 vs. 0.16±0.05d -1 , respectively). Additionally, CMs transformed 16.1±8.0-times more mass than BMs owing to continuous-feed operation. CMs are concluded to yield more reliable kinetic estimates because of much higher data density stemming from long-term, steady-state conditions. Since information from BMs and CMs is valuable and complementary, treatability studies should report kinetic data from both when available. This first systematic investigation of BMs and CMs highlights the need for a more unified framework for data use and reporting in treatability studies informing decision-making for field-scale groundwater remediation. Copyright © 2016 Elsevier B.V. All rights reserved.

Prolonged swimming performance of northern squawfish

USGS Publications Warehouse

Mesa, Matthew G.; Olson, Todd M.

1993-01-01

We determined the prolonged swimming performance of two size-classes of northern squawfish Ptychocheilus oregonensis at 12 and 18°C. The percentage of fish fatigued was positively related to water velocity and best described by an exponential model. At 12°C, the velocity at which 50% of the fish fatigued (FV50) was estimated to be 2.91 fork lengths per second (FL/s; 100 cm/s) for medium-sized fish (30–39 cm) and 2.45 FL/s (104 cm/s) for large fish (40–49 cm). At 18°C, estimated FV50 was 3.12 FL/s (107 cm/s) for medium fish and 2.65 FL/s (112 cm/s) for large fish. Rate of change in percent fatigue was affected by fish size and water temperature. Large fish fatigued at a higher rate than medium-sized fish; all fish fatigued faster at 12 than at 18°C. The mean times to fatigue at velocities of 102–115 cm/s ranged from 14 to 28 min and were not affected by fish size or water temperature. Our results indicate that water velocities from 100 to 130 cm/s may exclude or reduce predation by northern squawfish around juvenile salmonid bypass outfalls at Columbia River dams, at least during certain times of the year. We recommend that construction or modification of juvenile salmonid bypass facilities place the outfall in an area of high water velocity and distant from eddies, submerged cover, and littoral areas.

Beam-dynamic effects at the CMS BRIL van der Meer scans

NASA Astrophysics Data System (ADS)

Babaev, A.

2018-03-01

The CMS Beam Radiation Instrumentation and Luminosity Project (BRIL) is responsible for the simulation and measurement of luminosity, beam conditions and radiation fields in the CMS experiment. The project is engaged in operating and developing new detectors (luminometers), adequate for the experimental conditions associated with high values of instantaneous luminosity delivered by the CERN LHC . BRIL operates several detectors based on different physical principles and technologies. Precise and accurate measurements of the delivered luminosity is of paramount importance for the CMS physics program. The absolute calibration of luminosity is achieved by the van der Meer method, which is carried out under specially tailored conditions. This paper presents models used to simulate of beam-dynamic effects arising due to the electromagnetic interaction of colliding bunches. These effects include beam-beam deflection and dynamic-β effect. Both effects are important to luminosity measurements and influence calibration constants at the level of 1-2%. The simulations are carried out based on 2016 CMS van der Meer scan data for proton-proton collisions at a center-of-mass energy of 13 TeV.

Experimental High Energy Physics Research

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

Hohlmann, Marcus

This final report summarizes activities of the Florida Tech High Energy Physics group supported by DOE under grant #DE-SC0008024 during the period June 2012 – March 2015. We focused on one of the main HEP research thrusts at the Energy Frontier by participating in the CMS experiment. We were exploiting the tremendous physics opportunities at the Large Hadron Collider (LHC) and prepared for physics at its planned extension, the High-Luminosity LHC. The effort comprised a physics component with analysis of data from the first LHC run and contributions to the CMS Phase-2 upgrades in the muon endcap system (EMU) formore » the High-Luminosity LHC. The emphasis of our hardware work was the development of large-area Gas Electron Multipliers (GEMs) for the CMS forward muon upgrade. We built a production and testing site for such detectors at Florida Tech to complement future chamber production at CERN. The first full-scale CMS GE1/1 chamber prototype ever built outside of CERN was constructed at Florida Tech in summer 2013. We conducted two beam tests with GEM prototype chambers at CERN in 2012 and at FNAL in 2013 and reported the results at conferences and in publications. Principal Investigator Hohlmann served as chair of the collaboration board of the CMS GEM collaboration and as co-coordinator of the GEM detector working group. He edited and authored sections of the detector chapter of the Technical Design Report (TDR) for the GEM muon upgrade, which was approved by the LHCC and the CERN Research Board in 2015. During the course of the TDR approval process, the GEM project was also established as an official subsystem of the muon system by the CMS muon institution board. On the physics side, graduate student Kalakhety performed a Z' search in the dimuon channel with the 2011 and 2012 CMS datasets that utilized 20.6 fb⁻¹ of p-p collisions at √s = 8 TeV. For the dimuon channel alone, the 95% CL lower limits obtained on the mass of a Z' resonance are 2770 GeV for a Z' with the same standard-model couplings as the Z boson. Our student team operated a Tier-3 cluster on the Open Science Grid (OSG) to support local CMS physics analysis and remote OSG activity. As a service to the HEP community, Hohlmann participated in the Snowmass effort over the course of 2013. Specifically, he acted as a liaison for gaseous detectors between the Instrumentation Frontier and the Energy Frontier and contributed to five papers and reports submitted to the summer study.« less

Significance of Medicare and Medicaid Programs for the Practice of Medicine

PubMed Central

DeWalt, Darren A.; Oberlander, Jonathan; Carey, Timothy S.; Roper, William L.

2005-01-01

The 1965 legislation that established Medicare and Medicaid declared that the Federal Government would not interfere in clinical medicine. Despite the original intent, Medicare and Medicaid have had tremendous influence on medical practice. In this article, we focus on four policy areas that illustrate the influence of CMS (and its predecessor agencies) on medical practice. We discuss the implications of the relationship between CMS and clinical medicine and how this relationship has changed over time. We conclude with thoughts about potential future efforts at CMS. PMID:17290639

Experimental parametric study of a biomimetic fish robot actuated by piezoelectric actuators

NASA Astrophysics Data System (ADS)

Wiguna, T.; Park, Hoon C.; Heo, S.; Goo, Nam S.

2007-04-01

This paper presents an experiment and parametric study of a biomimetic fish robot actuated by the Lightweight Piezocomposite Actuator (LIPCA). The biomimetic aspects in this work are the oscillating tail beat motion and shape of caudal fin. Caudal fins that resemble fins of BCF (Body and Caudal Fin) mode fish were made in order to perform parametric study concerning the effect of caudal fin characteristics on thrust production at an operating frequency range. The observed caudal fin characteristics are the shape, stiffness, area, and aspect ratio. It is found that a high aspect ratio caudal fin contributes to high swimming speed. The robotic fish propelled by artificial caudal fins shaped after thunniform-fish and mackerel caudal fins, which have relatively high aspect ratio, produced swimming speed as high as 2.364 cm/s and 2.519 cm/s, respectively, for a 300 V p-p input voltage excited at 0.9 Hz. Thrust performance of the biomimetic fish robot is examined by calculating Strouhal number, Froude number, Reynolds number, and power consumption.

Assessing the ecological base flow in an experimental watershed of Central Taiwan

NASA Astrophysics Data System (ADS)

Wei, Chiang; Yang, Ping-Shih; Tian, Pei-Ling

2010-05-01

The ecological base flow is crucial for the assessment and design for habitat rehabilitation and recovery. The amount of discharge affects the aquatic creatures and may damage the existence and balance of the community under extreme low conditions. Aquatic insect is selected as the target species in this study to evaluate the influence of the discharge and to estimate the ecological base flow. The distribution of the number of species and abundance (density) versus discharge is assessed to define the critical discharge. A stream located at the alpine area in central Taiwan is selected as the study area to evaluate the base flow. From the preliminary data (Aug 2008 to May 2009) collected from Creek C of Sitou watershed (area: 1.3 km^2) shows that the abundance of several species varies with the discharge. The dominate family and genus of aquatic insects is Baetidae (Order Ephemeroptera) and Baetis spp. that accounts for 26.3 and 17.2 %, respectively. The Hilsenhoff family biotic index (FBI) shows that the water quality is classified to "Excellent" and "Good" level while the EPT Index (Index of three orders: Ephemeroptera, Plecoptera, and Trichoptera) indicates that the stream is non-polluted. The discharge of base flow interpreted from the 90%, 95% and 96% curve of duration for the daily discharge is 0.1582, 0.0476 and 0.0378 cms; the threshold value evaluated by curve of abundance vs. discharge is 0.0154 cms. Consistent observations are yet to be collected to yield more accurate results.

Delayed expression of SAGs correlates with longevity in CMS wheat plants compared to its fertile plants.

PubMed

Semwal, Vimal Kumar; Singh, Bhupinder; Khanna-Chopra, Renu

2014-04-01

Reproductive sinks regulate monocarpic senescence in crop plants. Monocarpic senescence was studied in wheat fertile (cv. HW 2041) and its isonuclear cytoplasmic male sterile (CMS) line. CMS plants exhibited slower rate of senescence accompanied by longer green leaf area duration and slower deceleration in chlorophyll, protein content, PN and rubisco content coupled with lower protease activities than fertile (F) plants. CMS plants also exhibited lower ROS levels and less membrane damage than F plants. CMS plants maintained better antioxidant defense, less oxidative damage in chloroplast and higher transcript levels of both rbcL and rbcS genes during senescence than F plants. F plants exhibited early induction and higher expression of SAGs like serine and cysteine proteases, glutamine synthetases GS1 and GS2, WRKY53 transcription factor and decline in transcript levels of CAT1 and CAT2 genes than CMS plants. Hence, using genetically fertile and its CMS line of wheat it is confirmed that delayed senescence in the absence of reproductive sinks is linked with slower protein oxidation, rubisco degradation and delayed activation of SAGs. Better antioxidant defense in chloroplasts at later stages of senescence was able to mitigate the deleterious effects of ROS in CMS plants. We propose that delayed increase in ROS in cytoplasmic male sterile wheat plants resulted in delayed activation of WRKY53, SAGs and the associated biochemical changes than fertile plants.

Pharmacokinetics of Chinese medicines: strategies and perspectives.

PubMed

Yan, Ru; Yang, Ying; Chen, Yijia

2018-01-01

The modernization and internationalization of Chinese medicines (CMs) are hampered by increasing concerns on the safety and the efficacy. Pharmacokinetic (PK) study is indispensable to establish concentration-activity/toxicity relationship and facilitate target identification and new drug discovery from CMs. To cope with tremendous challenges rooted from chemical complexity of CMs, the classic PK strategies have evolved rapidly from PK study focusing on marker/main drug components to PK-PD correlation study adopting metabolomics approaches to characterize associations between disposition of global drug-related components and host metabolic network shifts. However, the majority of PK studies of CMs have adopted the approaches tailored for western medicines and focused on the systemic exposures of drug-related components, most of which were found to be too low to account for the holistic benefits of CMs. With an area under concentration-time curve- or activity-weighted approach, integral PK attempts to understand the PK-PD relevance with the integrated PK profile of multiple co-existing structural analogs (prototyes/metabolites). Cellular PK-PD complements traditional PK-PD when drug targets localize inside the cells, instead of at the surface of cell membrane or extracellular space. Considering the validated clinical benefits of CMs, reverse pharmacology-based reverse PK strategy was proposed to facilitate target identification and new drug discovery. Recently, gut microbiota have demonstrated multifaceted roles in drug efficacy/toxicity. In traditional oral intake, the presystemic interactions of CMs with gut microbiota seem inevitable, which can contribute to the holistic benefits of CMs through biotransforming CMs components, acting as the peripheral target, and regulating host drug disposition. Hence, we propose a global PK-PD approach which includes the presystemic interaction of CMs with gut microbiota and combines omics with physiologically based pharmacokinetic modeling to offer a comprehensive understanding of the PK-PD relationship of CMs. Moreover, validated clinical benefits of CMs and poor translational potential of animal PK data urge more research efforts in human PK study.

Naja nigricollis CMS-9 enhances the mitochondria-mediated death pathway in adaphostin-treated human leukaemia U937 cells.

PubMed

Chen, Ying-Jung; Wang, Jeh-Jeng; Chang, Long-Sen

2011-11-01

1. The aim of the present study was to explore the effect of the Naja nigricollis phospholipase A(2) CMS-9 on adaphostin-induced death of human leukaemia U937 cells. 2. Leukaemia U937 cells (Bcr/Abl-negative cells) were treated with adaphostin (0-10 μmol/L) and CMS-9 (0-1 μmol/L). The effects of CMS-9, adaphostin and their combination on cell viability, the generation reactive oxygen species (ROS), [Ca(2+) ](i) , p38 mitogen-activated protein kinase (MAPK) activation, Akt and extracellular signal-regulated kinase (ERK) inactivation, mitochondrial membrane potential (ΔΨ(m) ) and Bcl-2 family proteins were analysed. 3. Both adaphostin and CMS-9 induced U937 cell apoptosis, characterized by dissipation of ΔΨ(m) and ROS generation. Combined treatment further increased ΔΨ(m) loss and reduced the viability of adaphostin-treated cells. Unlike in CMS-9-treated cells, in adaphostin-treated cells ROS-induced increases in [Ca(2+) ](i) were observed. CMS-9-induced ROS generation resulted in p38 MAPK activation, whereas adaphostin treatment elicited ROS/Ca(2+) -mediated inactivation of Akt and ERK. Moreover, Akt was found to be involved in ERK phosphorylation. Suppression of p38 MAPK activation blocked CMS-9-induced ΔΨ(m) loss and Bcl-xL downregulation. Overexpression of constitutively active Akt and mitogen-activated protein kinase kinase (MEK) 1 rescued adaphostin-induced ΔΨ(m) loss and Bcl-2 downregulation. Similarly, CMS-9 augmented adaphostin toxicity in human leukaemia K562 cells via increased mitochondrial alterations. 4. The results suggest that two distinct pathways mediate adaphostin- and CMS-9-induced mitochondrial damage (i.e. the ROS-Ca(2+) -Akt-ERK and ROS-p38 MAPK pathways, respectively). These distinct pathway explain the augmentation by CMS-9 of ΔΨ(m) loss and apoptosis in adaphostin-treated U937 cells. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

Cognitive Models for Integrating Testing and Instruction, Phase II. Methodology Program.

ERIC Educational Resources Information Center

Quellmalz, Edys S.; Shaha, Steven

The potential of a cognitive model task analysis scheme (CMS) that specifies features of test problems shown by research to affect performance is explored. CMS describes the general skill area and the generic task or problem type. It elaborates features of the problem situation and required responses found by research to influence performance.…

42 CFR 422.312 - Announcement of annual capitation rate, benchmarks, and methodology changes.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Monday in April each year, CMS announces to MA organizations and other interested parties the following information for each MA payment area for the following calendar year: (i) The annual MA capitation rate. (ii... annual, coordinated election period under § 422.62(a)(2), CMS will announce to MA organizations and other...

42 CFR 422.312 - Announcement of annual capitation rate, benchmarks, and methodology changes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Monday in April each year, CMS announces to MA organizations and other interested parties the following information for each MA payment area for the following calendar year: (i) The annual MA capitation rate. (ii... annual, coordinated election period under § 422.62(a)(2), CMS will announce to MA organizations and other...

Analyzing the Use of Concept Maps in Computer Science: A Systematic Mapping Study

ERIC Educational Resources Information Center

dos Santos, Vinicius; de Souza, Érica F.; Felizardo, Katia R; Vijaykumar, Nandamudi L.

2017-01-01

Context: concept Maps (CMs) enable the creation of a schematic representation of a domain knowledge. For this reason, CMs have been applied in different research areas, including Computer Science. Objective: the objective of this paper is to present the results of a systematic mapping study conducted to collect and evaluate existing research on…

Tailoring Mathematical Models to Stem-Cell Derived Cardiomyocyte Lines Can Improve Predictions of Drug-Induced Changes to Their Electrophysiology.

PubMed

Lei, Chon Lok; Wang, Ken; Clerx, Michael; Johnstone, Ross H; Hortigon-Vinagre, Maria P; Zamora, Victor; Allan, Andrew; Smith, Godfrey L; Gavaghan, David J; Mirams, Gary R; Polonchuk, Liudmila

2017-01-01

Human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) have applications in disease modeling, cell therapy, drug screening and personalized medicine. Computational models can be used to interpret experimental findings in iPSC-CMs, provide mechanistic insights, and translate these findings to adult cardiomyocyte (CM) electrophysiology. However, different cell lines display different expression of ion channels, pumps and receptors, and show differences in electrophysiology. In this exploratory study, we use a mathematical model based on iPSC-CMs from Cellular Dynamic International (CDI, iCell), and compare its predictions to novel experimental recordings made with the Axiogenesis Cor.4U line. We show that tailoring this model to the specific cell line, even using limited data and a relatively simple approach, leads to improved predictions of baseline behavior and response to drugs. This demonstrates the need and the feasibility to tailor models to individual cell lines, although a more refined approach will be needed to characterize individual currents, address differences in ion current kinetics, and further improve these results.

Synergistic effect of estradiol and fluoxetine in young adult and middle-aged female rats in two models of experimental depression.

PubMed

Récamier-Carballo, Soledad; Estrada-Camarena, Erika; Reyes, Rebeca; Fernández-Guasti, Alonso

2012-08-01

The antidepressant effect of estrogens combined with antidepressants is controversial: some preclinical data showed that estrogens facilitate the effect of antidepressants in the forced swimming test (FST) in young adult rats, while others failed to find such effect in middle-aged rats in the chronic mild stress (CMS) model. In clinics similar differences were reported and may be due to the compounds, the depression model or type of depression, the experimental design, and the age of the subjects or the women's menopause stage. The objective of this study was to analyze the antidepressant-like effect of the combination of 17β-estradiol (E(2)) and fluoxetine (FLX) in young adults (2-4 months) and middle-aged (12-14 months) ovariectomized (OVX) rats in two experimental models: FST and CMS. E(2) (5 and 10 μg/rat) and FLX (2.5 and 10 mg/kg) per se dose-dependently reduced immobility in both age groups and, in young adults both compounds increased swimming, whereas in middle-aged rats they increased swimming and climbing. Analysis of the antidepressant-like effect of the combination of suboptimal doses of FLX (1.25 mg/kg) and E(2) (2.5 μg/rat) showed a decrease in immobility and an increase in swimming in both age groups. In the CMS, chronic E(2) (2.5 μg/rat) with FLX (1.25 mg/kg) augmented relative sucrose intake, but middle-aged rats responded 2 weeks earlier than young adults. These results show that the antidepressant-like effect of the combination of E(2) and FLX in young adult and middle-aged female rats is evidenced in the two animal models of depression: FST and CMS. Copyright © 2012 Elsevier B.V. All rights reserved.

Experimental Verification of Material Flammability in Space

NASA Technical Reports Server (NTRS)

Ivanov, A. V.; Balashov, Y. V.; Andreeva, T. V.; Melikhov, A. S.

1999-01-01

The flammability in microgravity of three US-furnished materials, Delrin, polymethylmethacrylate (PMMA), and high-density polyethylene, was determined using a Russian-developed combustion tunnel on Mir. Four 4.5-mm-diameter cylindrical samples of each plastic were ignited under concurrent airflow (in the direction of flame spread) with velocities from no flow to 8.5 cm/s. The test results identify a limiting air-flow velocity V(sub lim) for each material, below which combustion ceases. Nominal values are V(sub lim) < 0.3 cm/s for Delrin, 0.5 cm/s for PMMA, and 0.3 to 0.5 cm/s for polyethylene. These values are lower than those obtained in prior ground testing. Nevertheless, they demonstrate that flow shutoff is effective for extinguishment in the microgravity environment of spacecraft. Microgravity test results also show that the plastic materials maintain a stable melt ball within the spreading flame zone. In general, as the concurrent flow velocity V decreases, the flame-spread rate V(sub F) decreases, from an average (for all three materials) of V(sub F)= 0.5-0.75 mm/s at V = 8.5 cm/s to V(sub F)= 0.05-0.01 mm/s at V = 0.3-0.5 cm/s. Also, as V decreases, the flames become less visible but expand, increasing the probability of igniting an adjacent surface.

Impact of calcium-sensitive dyes on the beating properties and pharmacological responses of human iPS-derived cardiomyocytes using the calcium transient assay.

PubMed

Kopljar, Ivan; Hermans, An N; Teisman, Ard; Gallacher, David J; Lu, Hua Rong

Calcium-based screening of hiPS-CMs is a useful preclinical safety evaluation platform with the ability to generate robust signals that facilitates high-throughput screening and data analysis. However, due to the potential inherent toxicities, it is important to understand potential effects of different calcium-sensitive dyes on the hiPS-CMs model. We compared three calcium-sensitive fluorescence dyes (Cal520, ACTOne and Calcium 5) for their impact on the variability, the beating properties and the pharmacological responses of hiPS-CMs using the Hamamatsu FDSS/μCell imaging platform. Direct effects of three dyes on the electrophysiological properties of hiPS-CMs were evaluated with the multi-electrode array (MEA) Axion Maestro platform. We propose a specific experimental protocol for each dye which gives the most optimal assay conditions to minimize variability and possible adverse effects. We showed that Cal520 had the smallest effect on hiPS-CMs together with the longest-lasting stable amplitude signal (up to 4 h). Although all dyes had a (minor) acute effect on hiPS-CMs, in the form of reduced beat rate and prolonged field potential duration, the selection of the dye did not influence the pharmacological response of four cardioactive drugs (dofetilide, moxifloxacin, nimodipine and isoprenaline). In conclusion, we have documented that different calcium sensitive dyes have only minor direct (acute) effects on hiPS-CMs with Cal520 showing the least effects and the longest lasting signal amplitude. Importantly, drug-induced pharmacological responses in hiPS-CMs were comparable between the three dyes. These findings should help further improve the robustness of the hiPS-CMs-based calcium transient assay as a predictive, preclinical cardiac safety evaluation tool. Copyright © 2018 Elsevier Inc. All rights reserved.

Thermal diffusivity of alpha-mercuric iodide

NASA Astrophysics Data System (ADS)

Burger, A.; Morgan, S. H.; Henderson, D. O.; Silberman, E.; Nason, D.

1991-01-01

The thermal diffusivity and its anisotropy is measured along the principal axes of tetragonal alpha-HgI2 semiconductor single crystals grown from vapor. The experiments are carried out using the flash pulse method. The results show that alpha(100-line-type) = 0.00370 sq cm/s + or - 3 percent and alpha(001-line-type = 0.00103 sq cm/s + or - 10 percent. Necessary corrections are made for the experimental variables of heat losses and finite pulse duration in the data analysis.

Numerical investigation of perforated polymer microcantilever sensor for contractile behavior of cardiomyocytes

NASA Astrophysics Data System (ADS)

Khoa Nguyen, Trieu; Lee, Dong-Weon; Lee, Bong-Kee

2017-06-01

In this study, a numerical investigation of microcantilever sensors for detecting the contractile behavior of cardiomyocytes (CMs) was performed. Recently, a novel surface-patterned perforated SU-8 microcantilever sensor has been developed for the preliminary screening of cardiac toxicity. From the contractile motion of the CMs cultured on the microcantilever surface, a macroscopic bending of the microcantilever was obtained, which is considered to reflect a physiological change. As a continuation of the previous research, a novel numerical method based on a surface traction model was proposed and verified to further understand the bending behavior of the microcantilevers. Effects of various factors, including surface traction magnitude, focal area of CMs, and stiffness of microcantilever, on the bending displacement were investigated. From static and transient analyses, the focal area was found to be the most crucial factor. In addition, the current result can provide a design guideline for various micromechanical devices based on the same principle.

Differences in Contractile Function of Myofibrils within Human Embryonic Stem Cell-Derived Cardiomyocytes vs. Adult Ventricular Myofibrils Are Related to Distinct Sarcomeric Protein Isoforms

PubMed Central

Iorga, Bogdan; Schwanke, Kristin; Weber, Natalie; Wendland, Meike; Greten, Stephan; Piep, Birgit; dos Remedios, Cristobal G.; Martin, Ulrich; Zweigerdt, Robert; Kraft, Theresia; Brenner, Bernhard

2018-01-01

Characterizing the contractile function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is key for advancing their utility for cellular disease models, promoting cell based heart repair, or developing novel pharmacological interventions targeting cardiac diseases. The aim of the present study was to understand whether steady-state and kinetic force parameters of β-myosin heavy chain (βMyHC) isoform-expressing myofibrils within human embryonic stem cell-derived cardiomyocytes (hESC-CMs) differentiated in vitro resemble those of human ventricular myofibrils (hvMFs) isolated from adult donor hearts. Contractile parameters were determined using the same micromechanical method and experimental conditions for both types of myofibrils. We identified isoforms and phosphorylation of main sarcomeric proteins involved in the modulation of force generation of both, chemically demembranated hESC-CMs (d-hESC-CMs) and hvMFs. Our results indicate that at saturating Ca2+ concentration, both human-derived contractile systems developed forces with similar rate constants (0.66 and 0.68 s−1), reaching maximum isometric force that was significantly smaller for d-hESC-CMs (42 kPa) than for hvMFs (94 kPa). At submaximal Ca2+-activation, where intact cardiomyocytes normally operate, contractile parameters of d-hESC-CMs and hvMFs exhibited differences. Ca2+ sensitivity of force was higher for d-hESC-CMs (pCa50 = 6.04) than for hvMFs (pCa50 = 5.80). At half-maximum activation, the rate constant for force redevelopment was significantly faster for d-hESC-CMs (0.51 s−1) than for hvMFs (0.28 s−1). During myofibril relaxation, kinetics of the slow force decay phase were significantly faster for d-hESC-CMs (0.26 s−1) than for hvMFs (0.21 s−1), while kinetics of the fast force decay were similar and ~20x faster. Protein analysis revealed that hESC-CMs had essentially no cardiac troponin-I, and partially non-ventricular isoforms of some other sarcomeric proteins, explaining the functional discrepancies. The sarcomeric protein isoform pattern of hESC-CMs had features of human cardiomyocytes at an early developmental stage. The study indicates that morphological and ultrastructural maturation of βMyHC isoform-expressing hESC-CMs is not necessarily accompanied by ventricular-like expression of all sarcomeric proteins. Our data suggest that hPSC-CMs could provide useful tools for investigating inherited cardiac diseases affecting contractile function during early developmental stages. PMID:29403388

77 FR 11677 - Medicaid Program; Review and Approval Process for Section 1115 Demonstrations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... experimental, pilot, and demonstration projects approved under section 1115 of the Social Security Act relating... selected provisions of section 1902 of the Act for experimental, pilot, or demonstration projects... application, and recommended that CMS allow the State to not post a complete application. The commenters noted...

Human breast adipose tissue: characterization of factors that change during tumor progression in human breast cancer.

PubMed

Fletcher, Sabrina Johanna; Sacca, Paula Alejandra; Pistone-Creydt, Mercedes; Coló, Federico Andrés; Serra, María Florencia; Santino, Flavia Eliana; Sasso, Corina Verónica; Lopez-Fontana, Constanza Matilde; Carón, Rubén Walter; Calvo, Juan Carlos; Pistone-Creydt, Virginia

2017-02-07

Adipose microenvironment is involved in signaling pathways that influence breast cancer. We aim to characterize factors that are modified: 1) in tumor and non tumor human breast epithelial cell lines when incubated with conditioned media (CMs) from human breast cancer adipose tissue explants (hATT) or normal breast adipose tissue explants (hATN); 2) in hATN-CMs vs hATT-CMs; 3) in the tumor associated adipocytes vs. non tumor associated adipocytes. We used hATN or hATT- CMs on tumor and non-tumor breast cancer cell lines. We evaluated changes in versican, CD44, ADAMTS1 and Adipo R1 expression on cell lines or in the different CMs. In addition we evaluated changes in the morphology and expression of these factors in slices of the different adipose tissues. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post-hoc tests were performed within each individual treatment. hATT-CMs increase versican, CD44, ADAMTS1 and Adipo R1 expression in breast cancer epithelial cells. Furthermore, hATT-CMs present higher levels of versican expression compared to hATN-CMs. In addition, we observed a loss of effect in cellular migration when we pre-incubated hATT-CMs with chondroitinase ABC, which cleaves GAGs chains bound to the versican core protein, thus losing the ability to bind to CD44. Adipocytes associated with the invasive front are reduced in size compared to adipocytes that are farther away. Also, hATT adipocytes express significantly higher amounts of versican, CD44 and Adipo R1, and significantly lower amounts of adiponectin and perilipin, unlike hATN adipocytes. We conclude that hATT secrete a different set of proteins compared to hATN. Furthermore, versican, a proteoglycan that is overexpressed in hATT-CMs compared to hATN-CMs, might be involved in the tumorogenic behavior observed in both cell lines employed. In addition, we may conclude that adipocytes from the tumor microenvironment show a less differentiated state than adipocytes from normal microenvironment. This would indicate a loss of normal functions in mature adipocytes (such as energy storage), in support of others that might favor tumor growth.

Direct Cardiac Reprogramming as a Novel Therapeutic Strategy for Treatment of Myocardial Infarction.

PubMed

Ma, Hong; Wang, Li; Liu, Jiandong; Qian, Li

2017-01-01

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds great promise as a novel therapy for the treatment of heart failure, a common and morbid disease that is usually caused by irreversible loss of functional cardiomyocytes (CMs). Recently, we and others showed that in a murine model of acute myocardial infarction, delivery of three transcription factors, Gata4, Mef2c, and Tbx5 converted endogenous cardiac fibroblasts into functional iCMs. These iCMs integrated electrically and mechanically with surrounding myocardium, resulting in a reduction in scar size and an improvement in heart function. Our findings suggest that iCM reprogramming may be a means of regenerating functional CMs in vivo for patients with heart disease. However, because relatively little is known about the factors that regulate iCM reprogramming, the applicability of iCM reprogramming is currently limited to the experimental settings in which it has been attempted. Specific hurdles include the relatively low conversion rate of iCMs and the need for reprogramming to occur in the context of acute injury. Therefore, before this treatment can become a viable therapy for human heart disease, the optimal condition for efficient iCM generation must be determined. Here, we provide a detailed protocol for both in vitro and in vivo iCM generation that has been optimized so far in our lab. We hope that this protocol will lay a foundation for future further improvement of iCM generation and provide a platform for mechanistic studies.

A search for a heavy Majorana neutrino and a radiation damage simulation for the HF detector

NASA Astrophysics Data System (ADS)

Wetzel, James William

A search for heavy Majorana neutrinos is performed using an event signature defined by two same-sign muons accompanied by two jets. This search is an extension of previous searches, (L3, DELPHI, CMS, ATLAS), using 19.7 fb -1 of data from the 2012 Large Hadron Collider experimental run collected by the Compact Muon Solenoid experiment. A mass window of 40-500 GeV/ c2 is explored. No excess events above Standard Model backgrounds is observed, and limits are set on the mixing element squared, |VmuN|2, as a function of Majorana neutFnrino mass. The Hadronic Forward (HF) Detector's performance will degrade as a function of the number of particles delivered to the detector over time, a quantity referred to as integrated luminosity and measured in inverse femtobarns (fb-1). In order to better plan detector upgrades, the CMS Forward Calorimetry Task Force (FCAL) group and the CMS Hadronic Calorimeter (HCAL) group have requested that radiation damage be simulated and the subsequent performance of the HF subdetector be studied. The simulation was implemented into both the CMS FastSim and CMS FullSim simulation packages. Standard calorimetry performance metrics were computed and are reported. The HF detector can expect to perform well through the planned delivery of 3000 fb-1.

CMS Use of a Data Federation

NASA Astrophysics Data System (ADS)

Bloom, Kenneth; Cms Collaboration

2014-06-01

CMS is in the process of deploying an Xrootd based infrastructure to facilitate a global data federation. The services of the federation are available to export data from half the physical capacity and the majority of sites are configured to read data over the federation as a back-up. CMS began with a relatively modest set of use-cases for recovery of failed local file opens, debugging and visualization. CMS is finding that the data federation can be used to support small scale analysis and load balancing. Looking forward we see potential in using the federation to provide more flexibility in the location workflows are executed as the difference between local access and wide area access are diminished by optimization and improved networking. In this presentation we discuss the application development work and the facility deployment work, the use-cases currently in production, and the potential for the technology moving forward.

Improvements of reinforced silica aerogel nanocomposites thermal properties for architecture applications.

PubMed

Saboktakin, Amin; Saboktakin, Mohammad Reza

2015-01-01

An 1,4-cis polybutadiene rubber/carboxymethyl starch (CMS)-based silica aerogel nanocomposites as a insulation material was developed that will provide superior thermal insulation properties, flexibility, toughness, durability of the parent polymer, yet with the low density and superior insulation properties associated with the aerogels. In this study, reinforced 1,4-cis polybutadiene-CMS-silica aerogel nanocomposites were prepared from a silica aerogel with a surface area 710 m(2) g(-1), a pore size of 25.3 nm and a pore volume of 4.7 cm(3) g(-1). The tensile properties and dynamic mechanical properties of 1,4-cis polybutadiene/CMS nanocomposites were systematically enhanced at low silica loading. Similar improvements in tensile modulus and strength have been observed for 1,4-cis polybutadiene/CMS mesoporous silica aerogel nanocomposites. Copyright © 2014 Elsevier B.V. All rights reserved.

Morphometric analysis of stab wounds by MSCT and MRI after the instillation of contrast medium.

PubMed

Fais, Paolo; Cecchetto, Giovanni; Boscolo-Berto, Rafael; Toniolo, Matteo; Viel, Guido; Miotto, Diego; Montisci, Massimo; Tagliaro, Franco; Giraudo, Chiara

2016-06-01

To analyze the morphology and depth of stab wounds experimentally produced on human legs amputated for medical reasons using multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) after the instillation of a single contrast medium solution (CMS). For morphological analysis, MSCT and MRI scans were performed before and after the instillation of CMS into the wound cavity. Depth measurements were performed on the sagittal view only after CMS instillation. Subsequently, each wound was dissected using the layer-by-layer technique and the depth was measured by a ruler. One-way between-groups pairwise analysis of variance (ANOVA) and Bland-Altman plot analysis were used for comparing radiological and anatomical measurements. Unenhanced MSCT images did not identify the wound channels, whereas unenhanced MRI evidenced the wound cavity in 50 % of cases. After the instillation of CMS, both MSCT and MRI depicted the wound channel in all the investigated stabbings, although the morphology of the cavity was irregular and did not resemble the shape of the blade. The radiological measurements of the wounds' depth, after the application of CMS, exhibited a high level of agreement (about 95 % at Bland-Altman plot analysis) with the anatomical measurements at dissection. A similar systematic underestimation, however, has been evidenced for MSCT (average 11.4 %; 95 % CI 7-17) and MRI (average 9.6 %; 95 % CI 6-13) data after the instillation of CMS with respect to wound dissection measurements. MSCT and MRI after the instillation of CMS can be used for depicting the morphometric features of stab wounds, although depth measurements are affected by a slight systematic underestimation compared to layer-by-layer dissection.

KMR kt-factorization procedure for the description of the LHCb forward hadron-hadron Z0 production at √{ s} = 13TeV

NASA Astrophysics Data System (ADS)

Modarres, M.; Masouminia, M. R.; Aminzadeh Nik, R.; Hosseinkhani, H.; Olanj, N.

2017-09-01

Quite recently, two sets of new experimental data from the LHCb and the CMS Collaborations have been published, concerning the production of the Z0 vector boson in hadron-hadron collisions with the center-of-mass energy ECM =√{ s} = 13TeV. On the other hand, in our recent work, we have conducted a set of semi-NLO calculations for the production of the electro-weak gauge vector bosons, utilizing the unintegrated parton distribution functions (UPDF) in the frameworks of Kimber-Martin-Ryskin (KMR) or Martin-Ryskin-Watt (MRW) and the kt-factorization formalism, concluding that the results of the KMR scheme are arguably better in describing the existing experimental data, coming from D0, CDF, CMS and ATLAS Collaborations. In the present work, we intend to follow the same semi-NLO formalism and calculate the rate of the production of the Z0 vector boson, utilizing the UPDF of KMR within the dynamics of the recent data. It will be shown that our results are in good agreement with the new measurements of the LHCb and the CMS Collaborations.

A comparison of NNLO QCD predictions with 7 TeV ATLAS and CMS data for V+jet processes

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

Boughezal, Radja; Liu, Xiaohui; Petriello, Frank

2016-06-17

Here, we perform a detailed comparison of next-to-next-to-leading order (NNLO) QCD predictions for the W+jet and Z+jet processes with 7 TeV experimental data from ATLAS and CMS. We observe excellent agreement between theory and data for most studied observables, which span several orders of magnitude in both cross section and energy. For some observables, such as the HT distribution, the NNLO QCD corrections are essential for resolving existing discrepancies between theory and data.

Noise Reduction Effect of Multiple-Sampling-Based Signal-Readout Circuits for Ultra-Low Noise CMOS Image Sensors.

PubMed

Kawahito, Shoji; Seo, Min-Woong

2016-11-06

This paper discusses the noise reduction effect of multiple-sampling-based signal readout circuits for implementing ultra-low-noise image sensors. The correlated multiple sampling (CMS) technique has recently become an important technology for high-gain column readout circuits in low-noise CMOS image sensors (CISs). This paper reveals how the column CMS circuits, together with a pixel having a high-conversion-gain charge detector and low-noise transistor, realizes deep sub-electron read noise levels based on the analysis of noise components in the signal readout chain from a pixel to the column analog-to-digital converter (ADC). The noise measurement results of experimental CISs are compared with the noise analysis and the effect of noise reduction to the sampling number is discussed at the deep sub-electron level. Images taken with three CMS gains of two, 16, and 128 show distinct advantage of image contrast for the gain of 128 (noise(median): 0.29 e - rms ) when compared with the CMS gain of two (2.4 e - rms ), or 16 (1.1 e - rms ).

Noise Reduction Effect of Multiple-Sampling-Based Signal-Readout Circuits for Ultra-Low Noise CMOS Image Sensors

PubMed Central

Kawahito, Shoji; Seo, Min-Woong

2016-01-01

This paper discusses the noise reduction effect of multiple-sampling-based signal readout circuits for implementing ultra-low-noise image sensors. The correlated multiple sampling (CMS) technique has recently become an important technology for high-gain column readout circuits in low-noise CMOS image sensors (CISs). This paper reveals how the column CMS circuits, together with a pixel having a high-conversion-gain charge detector and low-noise transistor, realizes deep sub-electron read noise levels based on the analysis of noise components in the signal readout chain from a pixel to the column analog-to-digital converter (ADC). The noise measurement results of experimental CISs are compared with the noise analysis and the effect of noise reduction to the sampling number is discussed at the deep sub-electron level. Images taken with three CMS gains of two, 16, and 128 show distinct advantage of image contrast for the gain of 128 (noise(median): 0.29 e−rms) when compared with the CMS gain of two (2.4 e−rms), or 16 (1.1 e−rms). PMID:27827972

Impact of the LHC beam abort kicker prefire on high luminosity insertion and CMS detector performance

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

A.I. Drozhdin, N.V. Mokhov and M. Huhtinen

1999-04-13

The effect of possible accidental beam loss in LHC on the IP5 insertion elements and CMS detector is studied via realistic Monte Carlo simulations. Such beam loss could be the consequence of an unsynchronized abort or in worst case an accidental prefire of one of the abort kicker modules. Simulations with the STRUCT code show that this beam losses would take place in the IP5 inner and outer triplets. MARS simulations of the hadronic and electro-magnetic cascades induced in such an event indicate severe heating of the inner triplet quadrupoles. In order to protect the IP5 elements, two methods aremore » proposed: a set of shadow collimators in the outer triplet and a prefired module compensation using a special module charged with an opposite voltage (antikicker). The remnants of the accidental beam loss entering the experimental hall have been used as input for FLUKA simulations in the CMS detector. It is shown that it is vital to take measures to reliably protect the expensive CMS tracker components.« less

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

Hong, A.; Mariwala, R.K.; Kane, M.S.

Experimental evidence is provided for adsorptive shape selectivity in the separation of the azeotrope between HF and 1,1,1,2-tetrafluoroethane (134a) over pyrolyzed poly(furfuryl alcohol)-derived carbogenic molecular sieve (PPFA-CMS). The separation can be accomplished over coconut charcoal or Carbosieve G on the basis of the differences in the extent of equilibrium adsorption of HF and 134a. On these adsorbents 134a is more strongly bound than HF, thus it elutes much more slowly from the bed. The heat of adsorption for 134a in the vicinity of 200 C on Carbosieve G is {approximately}8.8 kcal/mol. In contrast, when the same azeotropic mixture is separatedmore » over PPFA-CMS prepared at 500 C, 134a is not adsorbed. As a result 134a elutes from the bed first, followed by HF. The reversal is brought about by the narrower pore size and pore size distribution of the PPFA-CMS versus that for Carbosieve G. Thus the separation over PPFA-CMS is an example of adsorbate shape selectivity and represents a limiting case of kinetic separation.« less

Brightness and uniformity measurements of plastic scintillator tiles at the CERN H2 test beam

NASA Astrophysics Data System (ADS)

Chatrchyan, S.; Sirunyan, A. M.; Tumasyan, A.; Litomin, A.; Mossolov, V.; Shumeiko, N.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Spilbeeck, A.; Alves, G. A.; Aldá Júnior, W. L.; Hensel, C.; Carvalho, W.; Chinellato, J.; De Oliveira Martins, C.; Matos Figueiredo, D.; Mora Herrera, C.; Nogima, H.; Prado Da Silva, W. L.; Tonelli Manganote, E. J.; Vilela Pereira, A.; Finger, M.; Finger, M., Jr.; Kveton, A.; Tomsa, J.; Adamov, G.; Tsamalaidze, Z.; Behrens, U.; Borras, K.; Campbell, A.; Costanza, F.; Gunnellini, P.; Lobanov, A.; Melzer-Pellmann, I.-A.; Muhl, C.; Roland, B.; Sahin, M.; Saxena, P.; Hegde, V.; Kothekar, K.; Pandey, S.; Sharma, S.; Beri, S. B.; Bhawandeep, B.; Chawla, R.; Kalsi, A.; Kaur, A.; Kaur, M.; Walia, G.; Bhattacharya, S.; Ghosh, S.; Nandan, S.; Purohit, A.; Sharan, M.; Banerjee, S.; Bhattacharya, S.; Chatterjee, S.; Das, P.; Guchait, M.; Jain, S.; Kumar, S.; Maity, M.; Majumder, G.; Mazumdar, K.; Patil, M.; Sarkar, T.; Juodagalvis, A.; Afanasiev, S.; Bunin, P.; Ershov, Y.; Golutvin, I.; Malakhov, A.; Moisenz, P.; Smirnov, V.; Zarubin, A.; Chadeeva, M.; Chistov, R.; Danilov, M.; Popova, E.; Rusinov, V.; Andreev, Yu.; Dermenev, A.; Karneyeu, A.; Krasnikov, N.; Tlisov, D.; Toropin, A.; Epshteyn, V.; Gavrilov, V.; Lychkovskaya, N.; Popov, V.; Pozdnyakov, I.; Safronov, G.; Toms, M.; Zhokin, A.; Baskakov, A.; Belyaev, A.; Boos, E.; Dubinin, M.; Dudko, L.; Ershov, A.; Gribushin, A.; Kaminskiy, A.; Klyukhin, V.; Kodolova, O.; Lokhtin, I.; Miagkov, I.; Obraztsov, S.; Petrushanko, S.; Savrin, V.; Snigirev, A.; Andreev, V.; Azarkin, M.; Dremin, I.; Kirakosyan, M.; Leonidov, A.; Terkulov, A.; Bitioukov, S.; Elumakhov, D.; Kalinin, A.; Krychkine, V.; Mandrik, P.; Petrov, V.; Ryutin, R.; Sobol, A.; Troshin, S.; Volkov, A.; Sekmen, S.; Medvedeva, T.; Rumerio, P.; Adiguzel, A.; Bakirci, N.; Boran, F.; Cerci, S.; Damarseckin, S.; Demiroglu, Z. S.; Dölek, F.; Dozen, C.; Dumanoglu, I.; Eskut, E.; Girgis, S.; Gokbulut, G.; Guler, Y.; Hos, I.; Kangal, E. E.; Kara, O.; Kayis Topaksu, A.; Işik, C.; Kiminsu, U.; Oglakci, M.; Onengut, G.; Ozdemir, K.; Ozturk, S.; Polatoz, A.; Sunar Cerci, D.; Tali, B.; Tok, U. G.; Topakli, H.; Turkcapar, S.; Zorbakir, I. S.; Zorbilmez, C.; Bilin, B.; Isildak, B.; Karapinar, G.; Murat Guler, A.; Ocalan, K.; Yalvac, M.; Zeyrek, M.; Atakisi, I. O.; Gülmez, E.; Kaya, M.; Kaya, O.; Koseyan, O. K.; Ozcelik, O.; Ozkorucuklu, S.; Tekten, S.; Yetkin, E. A.; Yetkin, T.; Cankocak, K.; Sen, S.; Boyarintsev, A.; Grynyov, B.; Levchuk, L.; Popov, V.; Sorokin, P.; Flacher, H.; Borzou, A.; Call, K.; Dittmann, J.; Hatakeyama, K.; Liu, H.; Pastika, N.; Buccilli, A.; Cooper, S. I.; Henderson, C.; West, C.; Arcaro, D.; Gastler, D.; Hazen, E.; Rohlf, J.; Sulak, L.; Wu, S.; Zou, D.; Hakala, J.; Heintz, U.; Kwok, K. H. M.; Laird, E.; Landsberg, G.; Mao, Z.; Yu, D. R.; Gary, J. W.; Ghiasi Shirazi, S. M.; Lacroix, F.; Long, O. R.; Wei, H.; Bhandari, R.; Heller, R.; Stuart, D.; Yoo, J. H.; Chen, Y.; Duarte, J.; Lawhorn, J. M.; Nguyen, T.; Spiropulu, M.; Winn, D.; Abdullin, S.; Apresyan, A.; Apyan, A.; Banerjee, S.; Chlebana, F.; Freeman, J.; Green, D.; Hare, D.; Hirschauer, J.; Joshi, U.; Lincoln, D.; Los, S.; Pedro, K.; Spalding, W. J.; Strobbe, N.; Tkaczyk, S.; Whitbeck, A.; Linn, S.; Markowitz, P.; Martinez, G.; Bertoldi, M.; Hagopian, S.; Hagopian, V.; Kolberg, T.; Baarmand, M. M.; Noonan, D.; Roy, T.; Yumiceva, F.; Bilki, B.; Clarida, W.; Debbins, P.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Miller, M.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Schmidt, I.; Snyder, C.; Southwick, D.; Tiras, E.; Yi, K.; Al-bataineh, A.; Bowen, J.; Castle, J.; McBrayer, W.; Murray, M.; Wang, Q.; Kaadze, K.; Maravin, Y.; Mohammadi, A.; Saini, L. K.; Baden, A.; Belloni, A.; Calderon, J. D.; Eno, S. C.; Feng, Y. B.; Ferraioli, C.; Grassi, T.; Hadley, N. J.; Jeng, G.-Y.; Kellogg, R. G.; Kunkle, J.; Mignerey, A.; Ricci-Tam, F.; Shin, Y. H.; Skuja, A.; Yang, Z. S.; Yao, Y.; Brandt, S.; D'Alfonso, M.; Hu, M.; Klute, M.; Niu, X.; Chatterjee, R. M.; Evans, A.; Frahm, E.; Kubota, Y.; Lesko, Z.; Mans, J.; Ruckstuhl, N.; Heering, A.; Karmgard, D. J.; Musienko, Y.; Ruchti, R.; Wayne, M.; Benaglia, A. D.; Mei, K.; Tully, C.; Bodek, A.; de Barbaro, P.; Galanti, M.; Garcia-Bellido, A.; Khukhunaishvili, A.; Lo, K. H.; Vishnevskiy, D.; Zielinski, M.; Agapitos, A.; Amouzegar, M.; Chou, J. P.; Hughes, E.; Saka, H.; Sheffield, D.; Akchurin, N.; Damgov, J.; De Guio, F.; Dudero, P. R.; Faulkner, J.; Gurpinar, E.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Mengke, T.; Muthumuni, S.; Undleeb, S.; Volobouev, I.; Wang, Z.; Goadhouse, S.; Hirosky, R.; Wang, Y.

2018-01-01

We study the light output, light collection efficiency and signal timing of a variety of organic scintillators that are being considered for the upgrade of the hadronic calorimeter of the CMS detector. The experimental data are collected at the H2 test-beam area at CERN, using a 150 GeV muon beam. In particular, we investigate the usage of over-doped and green-emitting plastic scintillators, two solutions that have not been extensively considered. We present a study of the energy distribution in plastic-scintillator tiles, the hit efficiency as a function of the hit position, and a study of the signal timing for blue and green scintillators.

Adsorption equilibrium and thermodynamics of CO2 and CH4 on carbon molecular sieves

NASA Astrophysics Data System (ADS)

Song, Xue; Wang, Li'ao; Ma, Xu; Zeng, Yunmin

2017-02-01

Carbon molecular sieves (CMS) are widely used in the separation of dioxide carbon and methane. In this research, three commercial CMS were utilized to analyze the pore structure and chemical properties. The adsorption isotherms of CO2 and CH4 were studied at 298 K, 308 K and 318 K over the pressure range of 0-1 MPa by an Intelligent Gravimetric analysis (IGA-100B, UK). Langmuir model was adopted to fit the experimental data. The working capacity and selectivity were employed to evaluate the adsorbents. The adsorption thermodynamics were discussed. The adsorbed amounts of both CO2 and CH4 are found to be highly related with the BET specific surface area and the volume of micropores, and also are interrelated with the total pore volume and micropore surface area. The standard enthalpy change (ΔHΘ), standard Gibbs free energy (ΔGΘ) and standard entropy change (ΔSΘ) at zero surface loading are negative, manifesting the adsorption process is exothermic and spontaneous, and the system tends to be ordered. With the increasing surface coverage, the absolute values of Gibbs free energy (ΔG) decrease whereas the absolute values of enthalpy change (ΔH) and entropy change(ΔS) increase. This indicates that as the adsorbed amount increases, the degree of the spontaneity reduces, the intermolecular forces among the adsorbate molecules increase, the orderliness of the system improves and the adsorbed amount approaches the maximum adsorbed capacity.

What are the roles of clinical nurses and midwife specialists?

PubMed

Wickham, Sheelagh

Research shows the increasing part the Clinical Nurse Specialist (CNS) plays in healthcare today. But what does a CNS actually do in their day-to day-work? This study, set in the Republic of Ireland, aimed to explore the CNS and clinical midwife specialist (CMS) roles in practice. Quantitative methodology was used to explore the roles and activities of the CNS and CMS. Following ethics approval, a valid and reliable questionnaire was circulated to the total population of CNS/CMS in Ireland. The data were analysed using SPSS. This study articulates the individual role elements and activity level. The findings show the CNS/CMS to be active in the roles of researcher, educator, communicator, change agent, leader and clinical specialist, but the level of activity varies between different roles and individual role elements. The CNS/CMS is seen as a valuable resource in health care today and has potential to have a positive effect on patient care. The majority of CNS/CMSs are active in varying roles but the analysis shows lesser activity in some areas, such as research. The findings merit further study on role activity and possible variables that influence role activity.

42 CFR 422.252 - Terminology.

Code of Federal Regulations, 2010 CFR

2010-10-01

... § 422.252 Terminology. Annual MA capitation rate means a county payment rate for an MA local area... to refer to the annual MA capitation rate. MA local area means a payment area consisting of county or equivalent area specified by CMS. MA monthly basic beneficiary premium means the premium amount an MA plan...

42 CFR 413.231 - Adjustment for wages.

Code of Federal Regulations, 2010 CFR

2010-10-01

... labor-related portion of the base rate to account for geographic differences in the area wage levels using an appropriate wage index (established by CMS) which reflects the relative level of hospital wages... area as defined in this paragraph (b). (1) Urban area means a Metropolitan Statistical Area or a...

42 CFR 431.424 - Evaluation requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... evaluations. Demonstration evaluations will include the following: (1) Quantitative research methods. (i... of appropriate evaluation strategies (including experimental and other quantitative and qualitative... demonstration. (ii) CMS will consider alternative evaluation designs when quantitative designs are technically...

42 CFR 431.424 - Evaluation requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... evaluations. Demonstration evaluations will include the following: (1) Quantitative research methods. (i... of appropriate evaluation strategies (including experimental and other quantitative and qualitative... demonstration. (ii) CMS will consider alternative evaluation designs when quantitative designs are technically...

42 CFR 431.424 - Evaluation requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... evaluations. Demonstration evaluations will include the following: (1) Quantitative research methods. (i... of appropriate evaluation strategies (including experimental and other quantitative and qualitative... demonstration. (ii) CMS will consider alternative evaluation designs when quantitative designs are technically...

Fast access to the CMS detector condition data employing HTML5 technologies

NASA Astrophysics Data System (ADS)

Pierro, Giuseppe Antonio; Cavallari, Francesca; Di Guida, Salvatore; Innocente, Vincenzo

2011-12-01

This paper focuses on using HTML version 5 (HTML5) for accessing condition data for the CMS experiment, evaluating the benefits and risks posed by the use of this technology. According to the authors of HTML5, this technology attempts to solve issues found in previous iterations of HTML and addresses the needs of web applications, an area previously not adequately covered by HTML. We demonstrate that employing HTML5 brings important benefits in terms of access performance to the CMS condition data. The combined use of web storage and web sockets allows increasing the performance and reducing the costs in term of computation power, memory usage and network bandwidth for client and server. Above all, the web workers allow creating different scripts that can be executed using multi-thread mode, exploiting multi-core microprocessors. Web workers have been employed in order to substantially decrease the web page rendering time to display the condition data stored in the CMS condition database.

Calf muscle involvement in Becker muscular dystrophy: when size does not matter.

PubMed

Monforte, Mauro; Mercuri, Eugenio; Laschena, Francesco; Ricci, Enzo; Tasca, Giorgio

2014-12-15

Calf hypertrophy is a common feature in Becker muscular dystrophy (BMD), and it is still debated to which extent fatty degeneration or true muscle hypertrophy account for it. We wanted to investigate the relative contribution of these two components using a simple image analysis approach and their possible correlation with disease severity. Twenty-nine BMD patients' MRI scans were analyzed. A semiquantitative visual score assessing fatty replacement of calf muscles (calf MRI score, CMS) was calculated and correlated with the cross sectional area (CSA) of lower leg posterior compartment muscles, digitally measured on acquired images. The correlation between CSA and CMS was not significant. CMS in contrast correlated with disease severity (p<0.001) while CSA did not (p=0.969). In BMD, a major contribution to calf hypertrophy is provided by real muscle hypertrophy rather than by fatty degeneration. CMS appears to be a potential surrogate marker of disease severity. Copyright © 2014 Elsevier B.V. All rights reserved.

The QuarkNet CMS masterclass: bringing the LHC to students

NASA Astrophysics Data System (ADS)

Cecire, Kenneth; McCauley, Thomas

2016-04-01

QuarkNet is an educational program which brings high school teachers and their students into the particle physics research community. The program supports research experiences and professional development workshops and provides inquiry-oriented investigations, some using real experimental data. The CMS experiment at the LHC has released several thousand proton-proton collision events for use in education and outreach. QuarkNet, in collaboration with CMS, has developed a physics masterclass and e-Lab based on this data. A masterclass is a day-long educational workshop where high school students travel to nearby universities and research laboratories. There they learn from LHC physicists about the basics of particle physics and detectors. They then perform a simple measurement using LHC data, and share their results with other students around the world via videoconference. Since 2011 thousands of students from over 25 countries have participated in the CMS masterclass as organized by QuarkNet and the International Particle Physics Outreach Group (IPPOG).We describe here the masterclass exercise: the physics, the online event display and database preparation behind it, the measurement the students undertake, their results and experiences, and future plans for the exercise.

42 CFR 422.2266 - Deemed approval.

Code of Federal Regulations, 2012 CFR

2012-10-01

... submitted by an MA organization with respect to an MA plan in an area, CMS is deemed not to have disapproved the distribution in all other areas covered by the MA plan and organization except with regard to any...

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

PubMed Central

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

2014-01-01

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

Results of a higgs boson searches in the ATLAS and CMS experiments at the large hadron collider at energies 7 and 8 TeV

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

Artamonov, A. A.; Epshteyn, V. S.; Gavrilov, V. B.

2016-05-15

Recent achievements of the ATLAS and CMS experiments at the Large Hadron Collider searching for a Higgs boson are summarized. A new particle with the mass of 125 GeV and properties expected for the Standard Model Higgs boson was discovered three years ago in these experiments in proton-proton collisions when analyzing part of the data taken at the centre-of-mass energies 7 TeV and 8 TeV in 2011 and 2012 year exposures. Today all the data are processed and fully analyzed. Experimental results of studies of individual Higgs boson decay channels as well as their combination to extract such properties asmore » mass, signal strength, coupling constants, spin and parity are reviewed. All experimental results are found to be compatible with the Standard Model predictions.« less

The quality of Medicaid and Medicare data obtained from CMS and its contractors: implications for pharmacoepidemiology.

PubMed

Leonard, Charles E; Brensinger, Colleen M; Nam, Young Hee; Bilker, Warren B; Barosso, Geralyn M; Mangaali, Margaret J; Hennessy, Sean

2017-04-26

Administrative claims of United States Centers for Medicare and Medicaid Services (CMS) beneficiaries have long been used in non-experimental research. While CMS performs in-house checks of these claims, little is known of their quality for conducting pharmacoepidemiologic research. We performed exploratory analyses of the quality of Medicaid and Medicare data obtained from CMS and its contractors. Our study population consisted of Medicaid beneficiaries (with and without dual coverage by Medicare) from California, Florida, New York, Ohio, and Pennsylvania. We obtained and compiled 1999-2011 data from these state Medicaid programs (constituting about 38% of nationwide Medicaid enrollment), together with corresponding national Medicare data for dually-enrolled beneficiaries. This descriptive study examined longitudinal patterns in: dispensed prescriptions by state, by quarter; and inpatient hospitalizations by federal benefit, state, and age group. We further examined discrepancies between demographic characteristics and disease states, in particular frequencies of pregnancy complications among men and women beyond childbearing age, and prostate cancers among women. Dispensed prescriptions generally increased steadily and consistently over time, suggesting that these claims may be complete. A commercially-available National Drug Code lookup database was able to identify the dispensed drug for 95.2-99.4% of these claims. Because of co-coverage by Medicare, Medicaid data appeared to miss a substantial number of hospitalizations among beneficiaries ≥ 45 years of age. Pregnancy complication diagnoses were rare in males and in females ≥ 60 years of age, and prostate cancer diagnoses were rare in females. CMS claims from five large states obtained directly from CMS and its contractors appeared to be of high quality. Researchers using Medicaid data to study hospital outcomes should obtain supplemental Medicare data on dual enrollees, even for non-elders. Not applicable.

Effect of Wind Velocity on Flame Spread in Microgravity

NASA Technical Reports Server (NTRS)

Prasad, Kuldeep; Olson, Sandra L.; Nakamura, Yuji; Fujita, Osamu; Nishizawa, Katsuhiro; Ito, Kenichi; Kashiwagi, Takashi; Simons, Stephen N. (Technical Monitor)

2002-01-01

A three-dimensional, time-dependent model is developed describing ignition and subsequent transition to flame spread over a thermally thin cellulosic sheet heated by external radiation in a microgravity environment. A low Mach number approximation to the Navier Stokes equations with global reaction rate equations describing combustion in the gas phase and the condensed phase is numerically solved. The effects of a slow external wind (1-20 cm/s) on flame transition are studied in an atmosphere of 35% oxygen concentration. The ignition is initiated at the center part of the sample by generating a line-shape flame along the width of the sample. The calculated results are compared with data obtained in the 10s drop tower. Numerical results exhibit flame quenching at a wind speed of 1.0 cm/s, two localized flames propagating upstream along the sample edges at 1.5 cm/s, a single line-shape flame front at 5.0 cm/s, three flames structure observed at 10.0 cm/s (consisting of a single line-shape flame propagating upstream and two localized flames propagating downstream along sample edges) and followed by two line-shape flames (one propagating upstream and another propagating downstream) at 20.0 cm/s. These observations qualitatively compare with experimental data. Three-dimensional visualization of the observed flame complex, fuel concentration contours, oxygen and reaction rate isosurfaces, convective and diffusive mass flux are used to obtain a detailed understanding of the controlling mechanism, Physical arguments based on lateral diffusive flux of oxygen, fuel depletion, oxygen shadow of the flame and heat release rate are constructed to explain the various observed flame shapes.

Divergent effects of adrenaline in human induced pluripotent stem cell-derived cardiomyocytes obtained from hypertrophic cardiomyopathy

PubMed Central

Prajapati, Chandra

2018-01-01

ABSTRACT Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease that affects the heart muscle with diverse clinical outcomes. HCM can cause sudden cardiac death (SCD) during or immediately after mild to rigorous physical activity in young patients. However, the mechanism causing SCD as a result of exercise remains unknown, but exercise-induced ventricular arrhythmias are thought to be responsible for this fatal consequence. To understand the disease mechanism behind HCM in a better way, we generated patient-specific induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from HCM patients carrying either the MYBPC3-Gln1061X or TPM1-Asp175Asn mutation. We extensively investigated the effects of low to high concentrations of adrenaline on action potential characteristics, and the occurrence of arrhythmias in the presence of various concentrations of adrenaline and in wash-out condition. We classified and quantified different types of arrhythmias observed in hiPSC-CMs, and found that the occurrence of arrhythmias was dependent on concentrations of adrenaline and positions of mutations in genes causing HCM. In addition, we observed ventricular tachycardia types of arrhythmias in hiPSC-CMs carrying the TPM1-Asp175Asn mutation. We additionally examined the antiarrhythmic potency of bisoprolol in HCM-specific hiPSC-CMs. However, bisoprolol could not reduce the occurrence of arrhythmias during administration or during the wash-out condition of adrenaline in HCM-specific hiPSC-CMs. Our study demonstrates hiPSC-CMs as a promising tool for studying HCM. The experimental design used in this study could be suitable and beneficial for studying other components and drugs related to cardiac disease in general. PMID:29361520

Brightness and uniformity measurements of plastic scintillator tiles at the CERN H2 test beam

DOE PAGES

Chatrchyan, S.; Sirunyan, A. M.; Tumasyan, A.; ...

2018-01-05

Here, we study the light output, light collection efficiency and signal timing of a variety of organic scintillators that are being considered for the upgrade of the hadronic calorimeter of the CMS detector. The experimental data are collected at the H2 test-beam area at CERN, using a 150 GeV muon beam. In particular, we investigate the usage of over-doped and green-emitting plastic scintillators, two solutions that have not been extensively considered. We present a study of the energy distribution in plastic-scintillator tiles, the hit efficiency as a function of the hit position, and a study of the signal timing formore » blue and green scintillators.« less

Brightness and uniformity measurements of plastic scintillator tiles at the CERN H2 test beam

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

Chatrchyan, S.; Sirunyan, A. M.; Tumasyan, A.

Here, we study the light output, light collection efficiency and signal timing of a variety of organic scintillators that are being considered for the upgrade of the hadronic calorimeter of the CMS detector. The experimental data are collected at the H2 test-beam area at CERN, using a 150 GeV muon beam. In particular, we investigate the usage of over-doped and green-emitting plastic scintillators, two solutions that have not been extensively considered. We present a study of the energy distribution in plastic-scintillator tiles, the hit efficiency as a function of the hit position, and a study of the signal timing formore » blue and green scintillators.« less

Large-area hexagonal silicon detectors for the CMS High Granularity Calorimeter

NASA Astrophysics Data System (ADS)

Pree, E.

2018-02-01

During the so-called Phase-2 Upgrade, the CMS experiment at CERN will undergo significant improvements to cope with the 10-fold luminosity increase of the High Luminosity LHC (HL-LHC) era. Especially the forward calorimetry will suffer from very high radiation levels and intensified pileup in the detectors. For this reason, the CMS collaboration is designing a High Granularity Calorimeter (HGCAL) to replace the existing endcap calorimeters. It features unprecedented transverse and longitudinal segmentation for both electromagnetic (CE-E) and hadronic (CE-H) compartments. The CE-E and a large fraction of CE-H will consist of a sandwich structure with silicon as active detector material. This paper presents an overview of the ongoing sensor development for the HGCAL and highlights important design features and measurement techniques. The design and layout of an 8-inch silicon sensor prototype is shown. The hexagonal sensors consist of 235 pads, each with an area of about 1 cm2. Furthermore, Synopsys TCAD simulations regarding the high voltage stability of the sensors for different geometric parameters are performed. Finally, two different IV characterisation methods are compared on the same sensor.

Single event effects on the APV25 front-end chip

NASA Astrophysics Data System (ADS)

Friedl, M.; Bauer, T.; Pernicka, M.

2003-03-01

The Compact Muon Solenoid (CMS) experiment at the Large Hadron Collider at CERN will include a Silicon Strip Tracker covering a sensitive area of 206 m2. About ten million channels will be read out by APV25 front-end chips, fabricated in the 0.25 μm deep submicron process. Although permanent damage is not expected within CMS radiation levels, transient Single Event Upsets are inevitable. Moreover, localized ionization can also produce fake signals in the analog circuitry. Eight APV25 chips were exposed to a high-intensity pion beam at the Paul Scherrer Institute (Villigen/CH) to study the radiation induced effects in detail. The results, which are compatible to similar measurements performed with heavy ions, are used to predict the chip error rate at CMS.

Novel MRI Contrast Agent from Magnetotactic Bacteria Enables In Vivo Tracking of iPSC-derived Cardiomyocytes.

PubMed

Mahmoudi, Morteza; Tachibana, Atsushi; Goldstone, Andrew B; Woo, Y Joseph; Chakraborty, Papia; Lee, Kayla R; Foote, Chandler S; Piecewicz, Stephanie; Barrozo, Joyce C; Wakeel, Abdul; Rice, Bradley W; Bell Iii, Caleb B; Yang, Phillip C

2016-06-06

Therapeutic delivery of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) represents a novel clinical approach to regenerate the injured myocardium. However, methods for robust and accurate in vivo monitoring of the iCMs are still lacking. Although superparamagnetic iron oxide nanoparticles (SPIOs) are recognized as a promising tool for in vivo tracking of stem cells using magnetic resonance imaging (MRI), their signal persists in the heart even weeks after the disappearance of the injected cells. This limitation highlights the inability of SPIOs to distinguish stem cell viability. In order to overcome this shortcoming, we demonstrate the use of a living contrast agent, magneto-endosymbionts (MEs) derived from magnetotactic bacteria for the labeling of iCMs. The ME-labeled iCMs were injected into the infarcted area of murine heart and probed by MRI and bioluminescence imaging (BLI). Our findings demonstrate that the MEs are robust and effective biological contrast agents to track iCMs in an in vivo murine model. We show that the MEs clear within one week of cell death whereas the SPIOs remain over 2 weeks after cell death. These findings will accelerate the clinical translation of in vivo MRI monitoring of transplanted stem cell at high spatial resolution and sensitivity.

Cardiomyogenic Differentiation of Human Dental Follicle-derived Stem Cells by Suberoylanilide Hydroxamic Acid and Their In Vivo Homing Property.

PubMed

Sung, Iel-Yong; Son, Han-Na; Ullah, Imran; Bharti, Dinesh; Park, Ju-Mi; Cho, Yeong-Cheol; Byun, June-Ho; Kang, Young-Hoon; Sung, Su-Jin; Kim, Jong-Woo; Rho, Gyu-Jin; Park, Bong-Wook

2016-01-01

The purpose of the present study was to investigate the in vitro cardiomyogenic differentiation potential of human dental follicle-derived stem cells (DFCs) under the influence of suberoylanilide hydroxamic acid (SAHA), a member of the histone deacetylase inhibitor family, and analyze the in vivo homing capacity of induced cardiomyocytes (iCMs) when transplanted systemically. DFCs from extracted wisdom teeth showed mesenchymal stem cell (MSC) characteristics such as plate adherent growing, expression of MSC markers (CD44, CD90, and CD105), and mesenchymal lineage-specific differentiation potential. Adding SAHA to the culture medium induced the successful in vitro differentiation of DFCs into cardiomyocytes. These iCMs expressed cardiomyogenic markers, including alpha-smooth muscle actin (α-SMA), cardiac muscle troponin T (TNNT2), Desmin, and cardiac muscle alpha actin (ACTC1) , at both the mRNA and protein level. For the assessment of homing capacity, PKH26 labeled iCMs were intraperitoneally injected (1×10 6 cells in 100 µL of PBS) into the experimental mice, and the ratios of PKH26 positive cells to the total number of injected cells, in multiple organs were determined. The calculated homing ratios, 14 days after systemic cell transplantation, were 5.6 ± 1.0%, 3.6 ± 1.1%, and 11.6 ± 2.7% in heart, liver, and kidney respectively. There was no difference in the serum levels of interleukin-2 and interleukin-10 at 14 days after transplantation, between the experimental (iCM injected) and control (no injection or PBS injection) groups. These results demonstrate that DFCs can be an excellent source for cardiomyocyte differentiation and regeneration. Moreover, the iCMs can be delivered into heart muscle via systemic administration without eliciting inflammatory or immune response. This can serve as the pilot study for further investigations into the in vitro cardiomyogenic differentiation potential of DFCs under the influence of SAHA and the in vivo homing capacity of the iCMs into the heart muscle, when injected systemically.

Exploiting volatile opportunistic computing resources with Lobster

NASA Astrophysics Data System (ADS)

Woodard, Anna; Wolf, Matthias; Mueller, Charles; Tovar, Ben; Donnelly, Patrick; Hurtado Anampa, Kenyi; Brenner, Paul; Lannon, Kevin; Hildreth, Mike; Thain, Douglas

2015-12-01

Analysis of high energy physics experiments using the Compact Muon Solenoid (CMS) at the Large Hadron Collider (LHC) can be limited by availability of computing resources. As a joint effort involving computer scientists and CMS physicists at Notre Dame, we have developed an opportunistic workflow management tool, Lobster, to harvest available cycles from university campus computing pools. Lobster consists of a management server, file server, and worker processes which can be submitted to any available computing resource without requiring root access. Lobster makes use of the Work Queue system to perform task management, while the CMS specific software environment is provided via CVMFS and Parrot. Data is handled via Chirp and Hadoop for local data storage and XrootD for access to the CMS wide-area data federation. An extensive set of monitoring and diagnostic tools have been developed to facilitate system optimisation. We have tested Lobster using the 20 000-core cluster at Notre Dame, achieving approximately 8-10k tasks running simultaneously, sustaining approximately 9 Gbit/s of input data and 340 Mbit/s of output data.

A Bayesian approach for calibrating probability judgments

NASA Astrophysics Data System (ADS)

Firmino, Paulo Renato A.; Santana, Nielson A.

2012-10-01

Eliciting experts' opinions has been one of the main alternatives for addressing paucity of data. In the vanguard of this area is the development of calibration models (CMs). CMs are models dedicated to overcome miscalibration, i.e. judgment biases reflecting deficient strategies of reasoning adopted by the expert when inferring about an unknown. One of the main challenges of CMs is to determine how and when to intervene against miscalibration, in order to enhance the tradeoff between costs (time spent with calibration processes) and accuracy of the resulting models. The current paper dedicates special attention to this issue by presenting a dynamic Bayesian framework for monitoring, diagnosing, and handling miscalibration patterns. The framework is based on Beta-, Uniform, or Triangular-Bernoulli models and classes of judgmental calibration theories. Issues regarding the usefulness of the proposed framework are discussed and illustrated via simulation studies.

Enhanced solution velocity between dark and light areas with horizontal tubes and triangular prism baffles to improve microalgal growth in a flat-panel photo-bioreactor.

PubMed

Yang, Zongbo; Cheng, Jun; Xu, Xiaodan; Zhou, Junhu; Cen, Kefa

2016-07-01

Novel horizontal tubes and triangular prism (HTTP) baffles that generate flow vortices were developed to increase solution velocity between dark and light areas and thus improve microalgal growth in a flat-panel photo-bioreactor. Solution velocity, mass-transfer coefficient, and mixing time were measured with a particle-imaging velocimeter, dissolved oxygen probes, and pH probes. The solution mass-transfer coefficient increased by 30% and mixing time decreased by 21% when the HTTP baffles were used. The solution velocity between dark and light areas increased from ∼0.9cm/s to ∼3.5cm/s, resulting in a decreased dark-light cycle period to one-fourth. This enhanced flashing light effect with the HTTP baffles dramatically increased microalgae biomass yield by 70% in the flat-panel photo-bioreactor. Copyright © 2016 Elsevier Ltd. All rights reserved.

Soluble curcumin amalgamated chitosan microspheres augmented drug delivery and cytotoxicity in colon cancer cells: In vitro and in vivo study.

PubMed

Jyoti, Kiran; Bhatia, Richa Kaur; Martis, Elvis A F; Coutinho, Evans C; Jain, Upendra Kumar; Chandra, Ramesh; Madan, Jitender

2016-12-01

In present investigation, initially curcumin was complexed with 2-HP-β-CD (curcumin-2-HP-β-CD-complex) in 1:1 ratio and later amalgamated with chitosan microspheres (curcumin-2-HP-β-CD-CMs) for selective delivery in colon only through oral route of administration. Various analytical, spectral and in-silico docking techniques revealed that the curcumin was deeply inserted in the 2-HP-β-CD cavity with apparent stability constant of 3.35×10 -3 M. Furthermore, the mean particle size of 6.8±2.6μm and +39.2±4.1mV surface charge of curcumin-2-HP-β-CD-complex-CMs in addition to encapsulation efficiency of about 79.8±6.3% exhibited that the tailored microspheres were optimum for colon delivery of curcumin. This was also demonstrated in dissolution testing and standard cell proliferation assay in which curcumin-2-HP-β-CD-complex-CMs exhibited maximum release in simulated colonic fluid (SCF, pH ∼7.0-8.0, almond emulsion-β-glucosidase) with improved therapeutic index in HT-29 cells. Consistently, curcumin-2-HP-β-CD-complex-CMs successively enhanced the colonic bio-distribution of curcumin by ∼8.36 folds as compared to curcumin suspension in preclinical pharmacokinetic studies. In conclusion, curcumin-2-HP-β-CD-complex-CMs warrant further in vivo tumor regression study to establish its therapeutic efficacy in experimental colon cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Morphological and genetic characterization of a new cytoplasmic male sterility system (oxa CMS) in stem mustard (Brassica juncea).

PubMed

Heng, Shuangping; Liu, Sansan; Xia, Chunxiu; Tang, HongYu; Xie, Fei; Fu, Tingdong; Wan, Zhengjie

2018-01-01

KEY MESSAGE: oxa CMS is a new cytoplasmic male sterility type in Brassica juncea. oxa CMS is a cytoplasmic male sterility (CMS) line that has been widely used in the production and cultivation of stem mustard in the southwestern China. In this study, different CMS-type specific mitochondrial markers were used to confirm that oxa CMS is distinct from the pol CMS, ogu CMS, nap CMS, hau CMS, tour CMS, Moricandia arvensis CMS, orf220-type CMS, etc., that have been previously reported in Brassica crops. Pollen grains of the oxa CMS line are sterile with a self-fertility rate of almost 0% and the sterility strain rate and sterility degree of oxa CMS is 100% due to a specific flower structure and flowering habit. Scanning electron microscopy revealed that most pollen grains in mature anthers of the oxa CMS line are empty, flat and deflated. Semi-thin section further showed that the abortive stage of anther development in oxa CMS is initiated at the late uninucleate stage. Abnormally vacuolated microspores caused male sterility in the oxa CMS line. This cytological study combined with marker-assisted selection showed that oxa CMS is a novel CMS type in stem mustard (Brassica juncea). Interestingly, the abortive stage of oxa CMS is later than those in other CMS types reported in Brassica crops, and there is no negative effect on the oxa CMS line growth period. This study demonstrated that this novel oxa CMS has a unique flower structure with sterile pollen grains at the late uninucleate stage. Our results may help to uncover the mechanism of oxa CMS in Brassica juncea.

Are computational models of any use to psychiatry?

PubMed

Huys, Quentin J M; Moutoussis, Michael; Williams, Jonathan

2011-08-01

Mathematically rigorous descriptions of key hypotheses and theories are becoming more common in neuroscience and are beginning to be applied to psychiatry. In this article two fictional characters, Dr. Strong and Mr. Micawber, debate the use of such computational models (CMs) in psychiatry. We present four fundamental challenges to the use of CMs in psychiatry: (a) the applicability of mathematical approaches to core concepts in psychiatry such as subjective experiences, conflict and suffering; (b) whether psychiatry is mature enough to allow informative modelling; (c) whether theoretical techniques are powerful enough to approach psychiatric problems; and (d) the issue of communicating clinical concepts to theoreticians and vice versa. We argue that CMs have yet to influence psychiatric practice, but that they help psychiatric research in two fundamental ways: (a) to build better theories integrating psychiatry with neuroscience; and (b) to enforce explicit, global and efficient testing of hypotheses through more powerful analytical methods. CMs allow the complexity of a hypothesis to be rigorously weighed against the complexity of the data. The paper concludes with a discussion of the path ahead. It points to stumbling blocks, like the poor communication between theoretical and medical communities. But it also identifies areas in which the contributions of CMs will likely be pivotal, like an understanding of social influences in psychiatry, and of the co-morbidity structure of psychiatric diseases. Copyright © 2011 Elsevier Ltd. All rights reserved.

Enhancing the public impact of the Higgs discovery and other fundamental physics research

NASA Astrophysics Data System (ADS)

Lidstrom, Suzy; Read, Alex; Parke, Stephen; Allen, Roland; Goldfarb, Steven; Mehlhase, Sascha; Ekelof, Tord; Walker, Alan

2014-03-01

The recent experimental discovery of a Higgs boson by the ATLAS and CMS collaborations at the LHC, together with the awarding of the 2013 Nobel Prize for its theoretical prediction, has presented an exceptional opportunity for public outreach regarding the goals and importance of fundamental research in physics. We discuss novel avenues for further extending this outreach in all areas. These range from tutorial papers addressing students and teachers to internet resources and presentations to unconventional, but captivating, educational materials such as musical videos and LEGO models. Interaction with active scientists can be particularly stimulating. We account how this was encouraged (by means such as badges inviting questions from the public) during Nobel week and afterwards. The 2013 Nobel Prize in Physics explained Physica Scripta, Royal Swedish Academy of Sciences.

Carbon Monitoring System Applications Framework: Lessons Learned from Stakeholder Engagement Activities

NASA Astrophysics Data System (ADS)

Sepulveda Carlo, E.; Escobar, V. M.; Delgado Arias, S.; Forgotson, C.

2017-12-01

The NASA Carbon Monitoring System initiated by U.S. Congress in 2010 is developing products that characterize and quantify carbon sources and sinks in the United States and the global tropics. In 2013, an applications effort was selected to engage potential end users and gather feedback about their data needs. For the past four years the CMS applications efforts has expanded and implemented a number of strategies to connect carbon scientists to decision-makers, contributing to the societal benefits of CMS data products. The applications efforts use crowd sourcing to collects feedback from stakeholders on challenges and lessons learned in the use of CMS data products. Some of the most common data needs from engaged organizations include above and below-ground biomass and fluxes in forestlands and wetlands, and greenhouse gas (GHG) emissions across all land use/cover and land use changes. Stakeholder organizations' needs for CMS data products support national GHG inventories following the Paris Agreement, carbon markets, and sub-national natural resources management and policies. The lessons learned report presents stakeholder specific applications, challenges, and successes from using CMS data products. To date, the most common uses of CMS products include: conservation efforts, emissions inventory, forestry and land cover applications, and carbon offset projects. The most common challenges include: the need for familiar and consistent products over time, budget constraints, and concern with uncertainty of modeled results. Recurrent recommendations from stakeholder indicate that CMS should provide high resolution (30m) and frequent data products updates (annually). The applications efforts have also helped identified success stories from different CMS projects, including the development of the GHG emissions inventory from Providence, RI, the improvement of the U.S. GHG Inventory though the use of satellite data, and the use of high resolution canopy cover maps for forestry, conservation, and ecosystem services applications in the tristate area of Maryland, Delaware and Pennsylvania. The presentation will discuss the applications framework methodology and strategy, as well as highlight some of the results and lessons learned from these applications efforts.

Comparison of the Frontier Distributed Database Caching System to NoSQL Databases

NASA Astrophysics Data System (ADS)

Dykstra, Dave

2012-12-01

One of the main attractions of non-relational “NoSQL” databases is their ability to scale to large numbers of readers, including readers spread over a wide area. The Frontier distributed database caching system, used in production by the Large Hadron Collider CMS and ATLAS detector projects for Conditions data, is based on traditional SQL databases but also adds high scalability and the ability to be distributed over a wide-area for an important subset of applications. This paper compares the major characteristics of the two different approaches and identifies the criteria for choosing which approach to prefer over the other. It also compares in some detail the NoSQL databases used by CMS and ATLAS: MongoDB, CouchDB, HBase, and Cassandra.

Comparison of the Frontier Distributed Database Caching System to NoSQL Databases

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

Dykstra, Dave

One of the main attractions of non-relational NoSQL databases is their ability to scale to large numbers of readers, including readers spread over a wide area. The Frontier distributed database caching system, used in production by the Large Hadron Collider CMS and ATLAS detector projects for Conditions data, is based on traditional SQL databases but also adds high scalability and the ability to be distributed over a wide-area for an important subset of applications. This paper compares the major characteristics of the two different approaches and identifies the criteria for choosing which approach to prefer over the other. It alsomore » compares in some detail the NoSQL databases used by CMS and ATLAS: MongoDB, CouchDB, HBase, and Cassandra.« less

Thermal and chemical evolution in the early Solar System as recorded by FUN CAIs: Part II - Laboratory evaporation of potential CMS-1 precursor material

NASA Astrophysics Data System (ADS)

Mendybaev, Ruslan A.; Williams, Curtis D.; Spicuzza, Michael J.; Richter, Frank M.; Valley, John W.; Fedkin, Alexei V.; Wadhwa, Meenakshi

2017-03-01

We present the results of laboratory experiments in which a forsterite-rich melt estimated to be a potential precursor of Allende CMS-1 FUN CAI was evaporated into vacuum for different lengths of time at 1900 °C. The evaporation of this melt resulted in residues that define trajectories in chemical as well as magnesium, silicon and oxygen isotopic composition space and come very close to the measured properties of CMS-1. The isotopic composition of the evaporation residues was also used to determine the kinetic isotopic fractionation factors [α2,1 (vapor-melt) defined as the ratio of isotopes 2 and 1 of a given element in the evaporating gas divided by their ratio in the evaporating source] for evaporation of magnesium (α25,24 for 25Mg/24Mg), silicon (α29,28 for 29Si/28Si) and oxygen (α18,16 for 18O/16O) from the forsterite-rich melt at 1900 °C. The values of α25,24 = 0.98383 ± 0.00033 and α29,28 = 0.99010 ± 0.00038 are essentially independent of change in the melt composition as evaporation proceeds. In contrast, α18,16 changes from 0.9815 ± 0.0016 to ∼0.9911 when the residual melt composition changes from forsteritic to melilitic. Using the determined values of α25,24 and α29,28 and present-day bulk chemical composition of the CMS-1, the composition of the precursor of the inclusion was estimated to be close to the clinopyroxene + spinel + forsterite assemblage condensed from a solar composition gas. The correspondence between the chemical composition and isotopic fractionation of experimental evaporation residues and the present-day bulk chemical and isotopic compositions of CMS-1 is evidence that evaporation played a major role in the chemical evolution of CMS-1.

Human induced pluripotent stem cell‐derived versus adult cardiomyocytes: an in silico electrophysiological study on effects of ionic current block

PubMed Central

Paci, M; Hyttinen, J; Rodriguez, B

2015-01-01

Background and Purpose Two new technologies are likely to revolutionize cardiac safety and drug development: in vitro experiments on human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) and in silico human adult ventricular cardiomyocyte (hAdultV‐CM) models. Their combination was recently proposed as a potential replacement for the present hERG‐based QT study for pharmacological safety assessments. Here, we systematically compared in silico the effects of selective ionic current block on hiPSC‐CM and hAdultV‐CM action potentials (APs), to identify similarities/differences and to illustrate the potential of computational models as supportive tools for evaluating new in vitro technologies. Experimental Approach In silico AP models of ventricular‐like and atrial‐like hiPSC‐CMs and hAdultV‐CM were used to simulate the main effects of four degrees of block of the main cardiac transmembrane currents. Key Results Qualitatively, hiPSC‐CM and hAdultV‐CM APs showed similar responses to current block, consistent with results from experiments. However, quantitatively, hiPSC‐CMs were more sensitive to block of (i) L‐type Ca2+ currents due to the overexpression of the Na+/Ca2+ exchanger (leading to shorter APs) and (ii) the inward rectifier K+ current due to reduced repolarization reserve (inducing diastolic potential depolarization and repolarization failure). Conclusions and Implications In silico hiPSC‐CMs and hAdultV‐CMs exhibit a similar response to selective current blocks. However, overall hiPSC‐CMs show greater sensitivity to block, which may facilitate in vitro identification of drug‐induced effects. Extrapolation of drug effects from hiPSC‐CM to hAdultV‐CM and pro‐arrhythmic risk assessment can be facilitated by in silico predictions using biophysically‐based computational models. PMID:26276951

Mismatch between cuticle deposition and area expansion in fruit skins allows potentially catastrophic buildup of elastic strain.

PubMed

Lai, Xiaoting; Khanal, Bishnu Prasad; Knoche, Moritz

2016-11-01

The continuous deposition of cutin and wax during leaf and fruit growth is crucial to alleviate elastic strain of the cuticle, minimize the risk of failure and maintain its barrier functions. The cuticular membrane (CM) is a lipoidal biopolymer that covers primary surfaces of terrestrial plants. CMs have barrier functions in water and solute transfer and pathogen invasion. These require intact CMs throughout growth. This is a challenge particularly for fruit, because they increase in area from initiation through to maturity. Our paper investigates the effects of cutin and wax deposition on strain buildup in the CM. We use developing fruits and leaves of apple (Malus × domestica) and sweet cherry (Prunus avium) as models. The hypothesis was that the continuous deposition of the CM prevents the buildup of excessive elastic strain in fruit and leaves. Strains were quantified from decreases in surface area of CMs after isolation from epidermal discs, after wax extraction and from increases in surface area during development. Cuticle mass per unit area increased throughout development in apple fruit, and leaves of apple and sweet cherry. In sweet cherry fruit, however, CM mass increased only initially, but thereafter decreased as the surface expanded rapidly. The release of strain on CM isolation was low in apple fruit and leaves and sweet cherry leaves, but high in sweet cherry fruit. Conversely, strains fixed by the deposition of wax and cutin were high in apple fruit and leaves and sweet cherry leaves, but low in sweet cherry fruit. Our results indicate that in expanding organs, deposition of cutin and wax in the CM allows conversion of elastic to plastic strain. Hence, any lack of such deposition allows buildup of high, potentially catastrophic, elastic strain.

Detection of the Diversity of Cytoplasmic Male Sterility Sources in Broccoli (Brassica Oleracea var. Italica) Using Mitochondrial Markers.

PubMed

Shu, Jinshuai; Liu, Yumei; Li, Zhansheng; Zhang, Lili; Fang, Zhiyuan; Yang, Limei; Zhuang, Mu; Zhang, Yangyong; Lv, Honghao

2016-01-01

Broccoli (Brassica oleracea var. italica) is an important commercial vegetable crop. As part of an efficient pollination system, cytoplasmic male sterility (CMS) has been widely used for broccoli hybrid production. Identifying the original sources of CMS in broccoli accessions has become an important part of broccoli breeding. In this study, the diversity of the CMS sources of 39 broccoli accessions, including 19 CMS lines and 20 hybrids, were analyzed using mitochondrial markers. All CMS accessions contained the ogu orf138-related DNA fragment and the key genes of nap CMS, pol CMS, and tour CMS were not detected. The 39 CMS accessions were divided into five groups using six orf138-related and two simple sequence repeat markers. We observed that ogu CMS R3 constituted 79.49% of the CMS sources. CMS6 and CMS26 were differentiated from the other accessions using a specific primer. CMS32 was distinguished from the other accessions based on a 78-nucleotide deletion at the same locus as the orf138-related sequence. When the coefficient was about 0.90, five CMS accessions (13CMS6, 13CMS23, 13CMS24, 13CMS37, and 13CMS39) exhibiting abnormal floral organs with poor seed setting were grouped together. The polymerase chain reaction amplification profiles for these five accessions differed from those of the other accessions. We identified eight useful molecular markers that can be used to detect CMS types during broccoli breeding. Our data also provide important information relevant to future studies on the possible origins and molecular mechanisms of CMS in broccoli.

Detection of the Diversity of Cytoplasmic Male Sterility Sources in Broccoli (Brassica Oleracea var. Italica) Using Mitochondrial Markers

PubMed Central

Shu, Jinshuai; Liu, Yumei; Li, Zhansheng; Zhang, Lili; Fang, Zhiyuan; Yang, Limei; Zhuang, Mu; Zhang, Yangyong; Lv, Honghao

2016-01-01

Broccoli (Brassica oleracea var. italica) is an important commercial vegetable crop. As part of an efficient pollination system, cytoplasmic male sterility (CMS) has been widely used for broccoli hybrid production. Identifying the original sources of CMS in broccoli accessions has become an important part of broccoli breeding. In this study, the diversity of the CMS sources of 39 broccoli accessions, including 19 CMS lines and 20 hybrids, were analyzed using mitochondrial markers. All CMS accessions contained the ogu orf138-related DNA fragment and the key genes of nap CMS, pol CMS, and tour CMS were not detected. The 39 CMS accessions were divided into five groups using six orf138-related and two simple sequence repeat markers. We observed that ogu CMS R3 constituted 79.49% of the CMS sources. CMS6 and CMS26 were differentiated from the other accessions using a specific primer. CMS32 was distinguished from the other accessions based on a 78-nucleotide deletion at the same locus as the orf138-related sequence. When the coefficient was about 0.90, five CMS accessions (13CMS6, 13CMS23, 13CMS24, 13CMS37, and 13CMS39) exhibiting abnormal floral organs with poor seed setting were grouped together. The polymerase chain reaction amplification profiles for these five accessions differed from those of the other accessions. We identified eight useful molecular markers that can be used to detect CMS types during broccoli breeding. Our data also provide important information relevant to future studies on the possible origins and molecular mechanisms of CMS in broccoli. PMID:27446156

Demyelinating evidences in CMS rat model of depression: a DTI study at 7 T.

PubMed

Hemanth Kumar, B S; Mishra, S K; Trivedi, R; Singh, S; Rana, P; Khushu, S

2014-09-05

Depression is among the most debilitating diseases worldwide. Long-term exposure to stressors plays a major role in development of human depression. Chronic mild stress (CMS) seems to be a valid animal model for depression. Diffusion tensor imaging (DTI) is capable of inferring microstructural abnormalities of the white matter and has shown to serve as non-invasive marker of specific pathology. We developed a CMS rat model of depression and validated with behavioral experiments. We measured the diffusion indices (mean diffusivity (MD), fractional anisotropy (FA), axial (λ∥) and radial (λ⊥) diffusivity) to investigate the changes in CMS rat brain during depression onset. Diffusion indices have shown to be useful to discriminate myelin damage from axon loss. DTI was performed in both control and CMS rats (n=10, in each group) and maps of FA, MD, λ∥ and λ⊥ diffusivity values were generated using in-house built software. The diffusion indices were calculated by region of interest (ROI) analysis in different brain regions like the frontal cortex, hippocampus, hypothalamus, cingulum, thalamus, caudate putamen, corpus callosum, cerebral peduncle and sensory motor cortex. The results showed signs of demyelination, reflected by increased MD, decreased FA and increased λ⊥. The results also suggest a possible role of edema or inflammation concerning the brain morphology in CMS rats. The overall finding using DTI suggests there might be a major role of loss of myelin sheath, which leads to disrupted connectivity between the limbic area and the prefrontal cortex during the onset of depression. Our findings indicate that interpretation of these indices may provide crucial information about the type and severity of mood disorders. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Research approach and first results on agglomerate compaction in protoplanetary dust simulation in the Cloud Manipulation System

NASA Astrophysics Data System (ADS)

Vedernikov, Andrei; Blum, Jurgen; Ingo Von Borstel, Olaf; Schraepler, Rainer; Balapanov, Daniyar; Cecere, Anselmo

2016-07-01

Nanometre and micrometre-sized solid particles are ubiquitous in space and on Earth - from galaxies, interstellar space, protoplanetary and debris disks to planetary rings and atmospheres, planetary surfaces, comets, interplanetary space, Earth's atmosphere. Apparently, the most intriguing problem in the picture of the formation of planets is the transition from individual microscopic dust grains to kilometre-sized planetesimals. Revealing the mechanisms of this transition is one of the main tasks of the European Space Agency's project Interaction in Cosmic and Atmospheric Particle Systems (ICAPS). It was found that Brownian motion driven agglomeration could not provide the transition within reasonable time scale. As a result, at this stage top scientific goals shifted towards forced agglomeration and concentration of particles, targeting revealing the onset of compaction, experimental study of the evolution of fractal dimensions, size and mass distribution, occurrence of bouncing. The main tasks comprise 1) development of the rapid agglomeration model 2) development of the experimental facilities creating big fractal-type agglomerates from 10 to 1000 μm from a cloud of micrometre-size grains; 3) experimental realization of the rapid agglomeration in microgravity and ground conditions; and 4) in situ investigation of the morphology, mobility, mechanical and optical properties of the free-floating agglomerates, including investigation of thermophoresis, photophoresis of the agglomerates and of the two-phase flow phenomena. To solve the experimental part of the tasks we developed a Cloud Manipulation System, realized as a breadboard (CMS BB) for long duration microgravity platforms and a simplified laboratory version (CMS LV) mostly oriented on short duration microgravity and ground tests. The new system is based on the use of thermophoresis, most favourable for cloud manipulation without creating additional particle-particle forces in the cloud with a possibility of growing single agglomerate out of the whole cloud. The cloud manipulation system additionally provides temperature stabilization or, on the contrary, high temperature variation in the observation volume; formation of controlled temperature gradients, intensive three-dimensional periodic shear flow or three-dimensional gas density pulsations of the contraction-expansion type; application of electrostatic gradients including electro dynamic balancing; imposing of photophoretic force, etc. Their choice and/or combination depend upon particular experimental task. Experiments on forced agglomeration in short duration microgravity conditions of the Bremen drop tower succeeded in rapid growth of extended agglomerates, formation of complex three-dimensional cloud patterns, allowed observing controlled cloud displacement, cloud trapping, particle separation with respect to their electrical charge. The breadboard (CMS BB) and the laboratory version of the Cloud Manipulation System (CMS LV) are new types of scientific instrument with high scientific potential. ESA PRODEX program, the Belgian Federal Science Policy Office, DLR project 50WM1223, ZARM Drop Tower Operation and Service Company Ltd. are greatly acknowledged.

Effects of lifestyle intervention using patient-centered cognitive behavioral therapy among patients with cardio-metabolic syndrome: a randomized, controlled trial.

PubMed

Zhang, Ying; Mei, Songli; Yang, Rui; Chen, Ling; Gao, Hang; Li, Li

2016-11-18

Cardio-metabolic syndrome (CMS) is a highly prevalent condition. There is an urgent need to identify effective and integrated multi-disciplinary approaches that can reduce risk factors for CMS. Sixty-two patients with a history of CMS were randomized 1:1 into two groups: a standard information -only group (control), or a self-regulated lifestyle waist circumference (patient-centered cognitive behavioral therapy) intervention group. A pretest and posttest, controlled, experimental design was used. Outcomes were measured at the baseline (week 0) and at the end of intervention (week 12). Comparisons were drawn between groups and over time. The mean (standard deviation) age of the subjects was 48.6 (5.8) years ranging from 32 to 63, and 56.9% of the participants were female. Both groups showed no significant differences in Demographic variables and the metabolic syndrome indicators at baseline. While the control group only showed modest improvement after 12 weeks, compared to baseline, the intervention group demonstrated significant improvement from baseline. This study controlled for patients' demographics and baseline characteristics when assessing the effects of intervention. After adjusting for age, education and baseline level, the experimental group and the control group were statistically significant different in the following post-treatment outcomes: WC (F = 35.96, P < 0.001), TG (F = 18.93, P < 0.001), RSBP (F = 33.89, P < 0.001) and SF-36(F = 157.93, P < 0.001). The results showed patients' age and education were not strong predictors of patients' outcome (including WC, TG, RSBP and SF-36). Lifestyle intervention on patient-centered cognitive behavioral therapy can improve the physical and mental health conditions among individuals reporting a history of cardio-metabolic syndrome, and possibly provided preliminary benefits for the treatment of CMS. Chinese Clinical Trial Register #, ChiCTR15006148 .

Comparative Gene Expression Analyses Reveal Distinct Molecular Signatures between Differentially Reprogrammed Cardiomyocytes.

PubMed

Zhou, Yang; Wang, Li; Liu, Ziqing; Alimohamadi, Sahar; Yin, Chaoying; Liu, Jiandong; Qian, Li

2017-09-26

Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) or directly reprogrammed from non-myocytes (induced cardiomyocytes [iCMs]) are promising sources for heart regeneration or disease modeling. However, the similarities and differences between iPSC-CMs and iCMs are still unknown. Here, we performed transcriptome analyses of beating iPSC-CMs and iCMs generated from cardiac fibroblasts (CFs) of the same origin. Although both iPSC-CMs and iCMs establish CM-like molecular features globally, iPSC-CMs exhibit a relatively hyperdynamic epigenetic status, whereas iCMs exhibit a maturation status that more closely resembles that of adult CMs. Based on gene expression of metabolic enzymes, iPSC-CMs primarily employ glycolysis, whereas iCMs utilize fatty acid oxidation as the main pathway. Importantly, iPSC-CMs and iCMs exhibit different cell-cycle status, alteration of which influenced their maturation. Therefore, our study provides a foundation for understanding the pros and cons of different reprogramming approaches. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

45 CFR 150.203 - Circumstances requiring CMS enforcement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Circumstances requiring CMS enforcement. 150.203... CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for... requiring CMS enforcement. CMS enforces HIPAA requirements to the extent warranted (as determined by CMS) in...

Kinetics of Supercritical Water Oxidation. SERDP Compliance Technical Thrust Area

DTIC Science & Technology

1996-01-01

main stream velocity ratio (vj/ Vrx ) and jet-to-main stream diameter ratio) were different for the two tees. As a result, the "fast" tee was providing...Opposed-Flow Tee with no Inserts: Organic/Water Oxidant/Water Feed Feed Flow Conditions: vj (cm/s) 20-64 vj/ Vrx = 0.2-0.25 _ Rej =905-2920 To Reactor...Oxidant/Water Feed New Side-Entry Tee with 0.01" ID inserts: Organic/Water Feed Flow Conditions: vi (cm/s) 775-2,500 vj/ Vrx = 7.5-9.3 Rej =5,700-18,000

The CMS muon system: status and upgrades for LHC Run-2 and performance of muon reconstruction with 13 TeV data

NASA Astrophysics Data System (ADS)

Battilana, C.

2017-01-01

The CMS muon system has played a key role for many physics results obtained from the LHC Run-1 and Run-2 data. During the Long Shutdown (2013-2014), as well as during the last year-end technical stop (2015-2016), significant consolidation and upgrades have been carried out on the muon detectors and on the L1 muon trigger. The algorithms for muon reconstruction and identification have also been improved for both the High-Level Trigger and the offline reconstruction. Results of the performance of muon detectors, reconstruction and trigger, obtained using data collected at 13 TeV centre-of-mass energy during the 2015 and 2016 LHC runs, will be presented. Comparison of simulation with experimental data will also be discussed where relevant. The system's state of the art performance will be shown, and the improvements foreseen to achieve excellent overall quality of muon reconstruction in CMS, in the conditions expected during the high-luminosity phase of Run-2, will be described.

One Year of FOS Measurements in CMS Experiment at CERN

NASA Astrophysics Data System (ADS)

Szillási, Zoltán; Buontempo, Salvatore; Béni, Noémi; Breglio, Giovanni; Cusano, Andrea; Laudati, Armando; Giordano, Michele; Saccomanno, Andrea; Druzhkin, Dmitry; Tsirou, Andromachi

Results are presented on the activity carried out by our research group, in collaboration with the SME Optosmart s.r.l. (an Italian spin-off company), on the application of Fiber Optic Sensor (FOS) techniques to monitor high-energy physics (HEP) detectors. Assuming that Fiber Bragg Grating sensors (FBGs) radiation hardness has been deeply studied for other field of application, we have applied the FBG technology to the HEP research domain. We present here the experimental evidences of the solid possibility to use such a class of sensors also in HEP detector very complex environmental side conditions. In particular we present more than one year data results of FBG measurements in the Compact Muon Solenoid (CMS) experiment set up at the CERN, where we have monitored temperatures (within CMS core) and strains in different locations by using FBG sensors during the detector operation with the Large Hadron Collider (LHC) collisions and high magnetic field. FOS data and FOS readout system stability and reliability is demonstrated, with continuous 24/24 h 7/7d data taking under severe and complex side conditions.

Testing the 2-TeV resonance with trileptons

DOE PAGES

Das, Arindam; Nagata, Natsumi; Okada, Nobuchika

2016-03-09

The CMS collaboration has reported a 2.8 excess in the search of the SU(2) R gauge bosons decaying through right-handed neutrinos into the two electron plus two jets (more » $eejj$) final states. This can be explained if the SU(2) Rcharged gauge bosons W$$±\\atop{R}$$ have a mass of around 2TeV and a right-handed neutrino with a mass of O(1)TeV mainly decays to electron. Indeed, recent results in several other experiments, especially that from the ATLAS diboson resonance search, also indicate signatures of such a 2TeV gauge boson. However, a lack of the same-sign electron events in the CMS $eejj$ search challenges the interpretation of the right-handed neutrino as a Majorana fermion. Taking this situation into account, in this paper, we consider a possibility of explaining the CMS eejj excess based on the SU(2) L ⓍSU(2) RⓍ U(1) B-L gauge theory with pseudo-Dirac neutrinos. We fi nd that both the CMS excess events and the ATLAS diboson anomaly can actually be explained in this framework without conflicting with the current experimental bounds. This setup in general allows sizable left-right mixing in both the charged gauge boson and neutrino sectors, which enables us to probe this model through the trilepton plus missing energy search at the LHC. It turns out that the number of events in this channel predicted in our model is in good agreement with that observed by the CMS collaboration. We also discuss prospects for testing this model at the LHC Run-II experiments.« less

CMS: A Web-Based System for Visualization and Analysis of Genome-Wide Methylation Data of Human Cancers

PubMed Central

Huang, Yi-Wen; Roa, Juan C.; Goodfellow, Paul J.; Kizer, E. Lynette; Huang, Tim H. M.; Chen, Yidong

2013-01-01

Background DNA methylation of promoter CpG islands is associated with gene suppression, and its unique genome-wide profiles have been linked to tumor progression. Coupled with high-throughput sequencing technologies, it can now efficiently determine genome-wide methylation profiles in cancer cells. Also, experimental and computational technologies make it possible to find the functional relationship between cancer-specific methylation patterns and their clinicopathological parameters. Methodology/Principal Findings Cancer methylome system (CMS) is a web-based database application designed for the visualization, comparison and statistical analysis of human cancer-specific DNA methylation. Methylation intensities were obtained from MBDCap-sequencing, pre-processed and stored in the database. 191 patient samples (169 tumor and 22 normal specimen) and 41 breast cancer cell-lines are deposited in the database, comprising about 6.6 billion uniquely mapped sequence reads. This provides comprehensive and genome-wide epigenetic portraits of human breast cancer and endometrial cancer to date. Two views are proposed for users to better understand methylation structure at the genomic level or systemic methylation alteration at the gene level. In addition, a variety of annotation tracks are provided to cover genomic information. CMS includes important analytic functions for interpretation of methylation data, such as the detection of differentially methylated regions, statistical calculation of global methylation intensities, multiple gene sets of biologically significant categories, interactivity with UCSC via custom-track data. We also present examples of discoveries utilizing the framework. Conclusions/Significance CMS provides visualization and analytic functions for cancer methylome datasets. A comprehensive collection of datasets, a variety of embedded analytic functions and extensive applications with biological and translational significance make this system powerful and unique in cancer methylation research. CMS is freely accessible at: http://cbbiweb.uthscsa.edu/KMethylomes/. PMID:23630576

CMS: a web-based system for visualization and analysis of genome-wide methylation data of human cancers.

PubMed

Gu, Fei; Doderer, Mark S; Huang, Yi-Wen; Roa, Juan C; Goodfellow, Paul J; Kizer, E Lynette; Huang, Tim H M; Chen, Yidong

2013-01-01

DNA methylation of promoter CpG islands is associated with gene suppression, and its unique genome-wide profiles have been linked to tumor progression. Coupled with high-throughput sequencing technologies, it can now efficiently determine genome-wide methylation profiles in cancer cells. Also, experimental and computational technologies make it possible to find the functional relationship between cancer-specific methylation patterns and their clinicopathological parameters. Cancer methylome system (CMS) is a web-based database application designed for the visualization, comparison and statistical analysis of human cancer-specific DNA methylation. Methylation intensities were obtained from MBDCap-sequencing, pre-processed and stored in the database. 191 patient samples (169 tumor and 22 normal specimen) and 41 breast cancer cell-lines are deposited in the database, comprising about 6.6 billion uniquely mapped sequence reads. This provides comprehensive and genome-wide epigenetic portraits of human breast cancer and endometrial cancer to date. Two views are proposed for users to better understand methylation structure at the genomic level or systemic methylation alteration at the gene level. In addition, a variety of annotation tracks are provided to cover genomic information. CMS includes important analytic functions for interpretation of methylation data, such as the detection of differentially methylated regions, statistical calculation of global methylation intensities, multiple gene sets of biologically significant categories, interactivity with UCSC via custom-track data. We also present examples of discoveries utilizing the framework. CMS provides visualization and analytic functions for cancer methylome datasets. A comprehensive collection of datasets, a variety of embedded analytic functions and extensive applications with biological and translational significance make this system powerful and unique in cancer methylation research. CMS is freely accessible at: http://cbbiweb.uthscsa.edu/KMethylomes/.

Hydro-metrologic assessment of October 2015 extreme precipitation event on Santee Experimental Forest Watersheds, SC

Treesearch

Devendra M. Amatya; Charles A. Harrison; Carl C. Trettin

2016-01-01

The extreme precipitation event on October 3-4, 2015, likely resulting from the convergence of a persistent the terrain, and thecirculation associated with Hurricane Joaquin off the eastern Atlantic Coast(http://cms.met.psu.edu/sref/severe/2015/04Oct2015.pdf) resulted...

42 CFR 412.212 - National rate.

Code of Federal Regulations, 2010 CFR

2010-10-01

... discharge classified within a DRG, the national rate equals the product of— (1) The national average... under § 412.60(b)) for that DRG. (d) Adjusting for different area wage levels. CMS adjusts the...

Dose-ranging pharmacokinetics of colistin methanesulphonate (CMS) and colistin in rats following single intravenous CMS doses.

PubMed

Marchand, Sandrine; Lamarche, Isabelle; Gobin, Patrice; Couet, William

2010-08-01

The aim of this study was to evaluate the effect of colistin methanesulphonate (CMS) dose on CMS and colistin pharmacokinetics in rats. Three rats per group received an intravenous bolus of CMS at a dose of 5, 15, 30, 60 or 120 mg/kg. Arterial blood samples were drawn at 0, 5, 15, 30, 60, 90, 120, 150 and 180 min. CMS and colistin plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of CMS and colistin were calculated by non-compartmental analysis. Linear relationships were observed between CMS and colistin AUCs to infinity and CMS doses, as well as between CMS and colistin C(max) and CMS doses. CMS and colistin pharmacokinetics were linear for a range of colistin concentrations covering the range of values encountered and recommended in patients even during treatment with higher doses.

Customized Noise-Stimulation Intensity for Bipedal Stability and Unipedal Balance Deficits Associated With Functional Ankle Instability

PubMed Central

Ross, Scott E.; Linens, Shelley W.; Wright, Cynthia J.; Arnold, Brent L.

2013-01-01

Context: Stochastic resonance stimulation (SRS) administered at an optimal intensity could maximize the effects of treatment on balance. Objective: To determine if a customized optimal SRS intensity is better than a traditional SRS protocol (applying the same percentage sensory threshold intensity for all participants) for improving double- and single-legged balance in participants with or without functional ankle instability (FAI). Design: Case-control study with an embedded crossover design. Setting: Laboratory. Patients or Other Participants: Twelve healthy participants (6 men, 6 women; age = 22 ± 2 years, height = 170 ± 7 cm, mass = 64 ± 10 kg) and 12 participants (6 men, 6 women; age = 23 ± 3 years, height = 174 ± 8 cm, mass = 69 ± 10 kg) with FAI. Intervention(s): The SRS optimal intensity level was determined by finding the intensity from 4 experimental intensities at the percentage sensory threshold (25% [SRS25], 50% [SRS50], 75% [SRS75], 90% [SRS90]) that produced the greatest improvement in resultant center-of-pressure velocity (R-COPV) over a control condition (SRS0) during double-legged balance. We examined double- and single-legged balance tests, comparing optimal SRS (SRSopt1) and SRS0 using a battery of center-of-pressure measures in the frontal and sagittal planes. Main Outcome Measure(s): Anterior-posterior (A-P) and medial-lateral (M-L) center-of-pressure velocity (COPV) and center-of-pressure excursion (COPE), R-COPV, and 95th percentile center-of-pressure area ellipse (COPA-95). Results: Data were organized into bins that represented optimal (SRSopt1), second (SRSopt2), third (SRSopt3), and fourth (SRSopt4) improvement over SRS0. The SRSopt1 enhanced R-COPV (P ≤ .05) over SRS0 and other SRS conditions (SRS0 = 0.94 ± 0.32 cm/s, SRSopt1 = 0.80 ± 0.19 cm/s, SRSopt2 = 0.88 ± 0.24 cm/s, SRSopt3 = 0.94 ± 0.25 cm/s, SRSopt4 = 1.00 ± 0.28 cm/s). However, SRS did not improve R-COPV over SRS0 when data were categorized by sensory threshold. Furthermore, SRSopt1 improved double-legged balance over SRS0 from 11% to 25% in all participants for the center-of-pressure frontal- and sagittal-plane assessments (P ≤ .05). The SRSopt1 also improved single-legged balance over SRS0 from 10% to 17% in participants with FAI for the center-of-pressure frontal- and sagittal-plane assessments (P ≤ .05). The SRSopt1 did not improve single-legged balance in participants with stable ankles. Conclusions: The SRSopt1 improved double-legged balance and transfers to enhancing single-legged balance deficits associated with FAI. PMID:23724774

Responses of bluegills and black crappies to dissolved oxygen, temperature, and current in backwater lakes of the upper Mississippi River during winter

USGS Publications Warehouse

Knights, B.C.; Johnson, B.L.; Sandheinrich, M.B.

1995-01-01

We conducted a radiotelemetry study to examine the effects of dissolved oxygen (DO), water temperature, and current velocity on winter habitat selection by bluegills Lepomis macrochirus and black crappies Pomoxis nigromaculatus in the Finger Lakes backwater complex, Pool 5, on the upper Mississippi River. When DO was above 2 mg/L, both species selected areas with water temperature greater than 1 degree C and undetectable current. As dissolved oxygen concentrations fell below 2 mg/L, fish moved to areas with higher DO, despite water temperatures of 1 degree C and lower and current velocities of 1 cm/s. Areas with water temperature less than 1 degree C and current velocity greater than 1 cm/s were avoided. To incorporate the winter habitat requirements of bluegills and black crappies into habitat restoration projects, we recommend designs that allow the inflow of oxygenated water to maintain adequate DO without substantially decreasing temperature and increasing current velocity.

Matrigel Mattress: A Method for the Generation of Single Contracting Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

PubMed

Feaster, Tromondae K; Cadar, Adrian G; Wang, Lili; Williams, Charles H; Chun, Young Wook; Hempel, Jonathan E; Bloodworth, Nathaniel; Merryman, W David; Lim, Chee Chew; Wu, Joseph C; Knollmann, Björn C; Hong, Charles C

2015-12-04

The lack of measurable single-cell contractility of human-induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) currently limits the utility of hiPSC-CMs for evaluating contractile performance for both basic research and drug discovery. To develop a culture method that rapidly generates contracting single hiPSC-CMs and allows quantification of cell shortening with standard equipment used for studying adult CMs. Single hiPSC-CMs were cultured for 5 to 7 days on a 0.4- to 0.8-mm thick mattress of undiluted Matrigel (mattress hiPSC-CMs) and compared with hiPSC-CMs maintained on a control substrate (<0.1-mm thick 1:60 diluted Matrigel, control hiPSC-CMs). Compared with control hiPSC-CMs, mattress hiPSC-CMs had more rod-shape morphology and significantly increased sarcomere length. Contractile parameters of mattress hiPSC-CMs measured with video-based edge detection were comparable with those of freshly isolated adult rabbit ventricular CMs. Morphological and contractile properties of mattress hiPSC-CMs were consistent across cryopreserved hiPSC-CMs generated independently at another institution. Unlike control hiPSC-CMs, mattress hiPSC-CMs display robust contractile responses to positive inotropic agents, such as myofilament calcium sensitizers. Mattress hiPSC-CMs exhibit molecular changes that include increased expression of the maturation marker cardiac troponin I and significantly increased action potential upstroke velocity because of a 2-fold increase in sodium current (INa). The Matrigel mattress method enables the rapid generation of robustly contracting hiPSC-CMs and enhances maturation. This new method allows quantification of contractile performance at the single-cell level, which should be valuable to disease modeling, drug discovery, and preclinical cardiotoxicity testing. © 2015 American Heart Association, Inc.

42 CFR 486.308 - Designation of one OPO for each service area.

Code of Federal Regulations, 2010 CFR

2010-10-01

... CMS establishing that— (1) The waiver is expected to increase organ donations; and (2) The waiver will... FURNISHED BY SUPPLIERS Requirements for Certification and Designation and Conditions for Coverage: Organ...

Vascular Endothelial Growth Factor Secretion by Nonmyocytes Modulates Connexin-43 Levels in Cardiac Organoids

PubMed Central

Iyer, Rohin K.; Odedra, Devang; Chiu, Loraine L.Y.; Vunjak-Novakovic, Gordana

2012-01-01

We previously showed that the sequential, but not simultaneous, culture of endothelial cells (ECs), fibroblasts (FBs), and cardiomyocytes (CMs) resulted in elongated, beating cardiac organoids. We hypothesized that the expression of Cx43 and contractile function are mediated by vascular endothelial growth factor (VEGF) released by nonmyocytes during the preculture period. Cardiac organoids (∼200 μm diameter) were cultivated in microchannels to enable rapid screening. Three experimental groups were formed: (i) Simultaneous Preculture (ECs+FBs for 48 h, followed by CMs), (ii) Sequential Preculture (ECs for 24 h, FBs for 24 h, followed by CMs), and (iii) Simultaneous Triculture (ECs+FBs+CMs). Controls included CMs only, FBs only, and ECs only groups, and preculture with ECs only or FBs only. The highest VEGF levels were found in the Preculture groups [Simultaneous Preculture, 8.9±2.7 ng/(mL·h−1); Sequential Preculture, 16.6±3.4 ng/(mL·h−1)], as compared with Simultaneous Triculture where VEGF was not detectable, as shown by enzyme-linked immunosorbent assay. Analytical flow cytometry showed that VEGFR2 was expressed by ECs (86%±2 VEGFR2+), FBs (44%±1 VEGFR2+), and CMs (49%±2 VEGFR2+), showing that all three cell types were capable of responding to changes in VEGF. Addition of anti-VEGF neutralizing IgG (0.4 μg/mL) to Simultaneous Preculture resulted in 3-fold decrease in Cx43 mRNA and 1.5-fold decrease in Cx43 protein, while Simultaneous Triculture supplemented with VEGF ligand (30 ng/mL) had a threefold increase in Cx43 mRNA and a twofold increase in Cx43 protein. Addition of a small molecule inhibitor of the VEGFR2 receptor (19.4 nM) to Sequential Preculture caused a 1.4-fold decrease in Cx43 mRNA and a 4.1-fold decrease in Cx43 protein. Cx43 was localized within CMs, and not within FBs or ECs. Enriched CM organoids and Sequential Preculture organoids grown in the presence of VEGFR2 inhibitor displayed low levels of Cx43 and poor functional properties. Taken together, these results suggest that endogenous VEGF-VEGFR2 signaling enhanced Cx43 expression and cardiac function in engineered cardiac organoids. PMID:22519405

Monitoring the CMS strip tracker readout system

NASA Astrophysics Data System (ADS)

Mersi, S.; Bainbridge, R.; Baulieu, G.; Bel, S.; Cole, J.; Cripps, N.; Delaere, C.; Drouhin, F.; Fulcher, J.; Giassi, A.; Gross, L.; Hahn, K.; Mirabito, L.; Nikolic, M.; Tkaczyk, S.; Wingham, M.

2008-07-01

The CMS Silicon Strip Tracker at the LHC comprises a sensitive area of approximately 200 m2 and 10 million readout channels. Its data acquisition system is based around a custom analogue front-end chip. Both the control and the readout of the front-end electronics are performed by off-detector VME boards in the counting room, which digitise the raw event data and perform zero-suppression and formatting. The data acquisition system uses the CMS online software framework to configure, control and monitor the hardware components and steer the data acquisition. The first data analysis is performed online within the official CMS reconstruction framework, which provides many services, such as distributed analysis, access to geometry and conditions data, and a Data Quality Monitoring tool based on the online physics reconstruction. The data acquisition monitoring of the Strip Tracker uses both the data acquisition and the reconstruction software frameworks in order to provide real-time feedback to shifters on the operational state of the detector, archiving for later analysis and possibly trigger automatic recovery actions in case of errors. Here we review the proposed architecture of the monitoring system and we describe its software components, which are already in place, the various monitoring streams available, and our experiences of operating and monitoring a large-scale system.

Postural Instability Induced by Visual Motion Stimuli in Patients With Vestibular Migraine

PubMed Central

Lim, Yong-Hyun; Kim, Ji-Soo; Lee, Ho-Won; Kim, Sung-Hee

2018-01-01

Patients with vestibular migraine are susceptible to motion sickness. This study aimed to determine whether the severity of posture instability is related to the susceptibility to motion sickness. We used a visual motion paradigm with two conditions of the stimulated retinal field and the head posture to quantify postural stability while maintaining a static stance in 18 patients with vestibular migraine and in 13 age-matched healthy subjects. Three parameters of postural stability showed differences between VM patients and controls: RMS velocity (0.34 ± 0.02 cm/s vs. 0.28 ± 0.02 cm/s), RMS acceleration (8.94 ± 0.74 cm/s2 vs. 6.69 ± 0.87 cm/s2), and sway area (1.77 ± 0.22 cm2 vs. 1.04 ± 0.25 cm2). Patients with vestibular migraine showed marked postural instability of the head and neck when visual stimuli were presented in the retinal periphery. The pseudo-Coriolis effect induced by head roll tilt was not responsible for the main differences in postural instability between patients and controls. Patients with vestibular migraine showed a higher visual dependency and low stability of the postural control system when maintaining quiet standing, which may be related to susceptibility to motion sickness. PMID:29930534

Postural Instability Induced by Visual Motion Stimuli in Patients With Vestibular Migraine.

PubMed

Lim, Yong-Hyun; Kim, Ji-Soo; Lee, Ho-Won; Kim, Sung-Hee

2018-01-01

Patients with vestibular migraine are susceptible to motion sickness. This study aimed to determine whether the severity of posture instability is related to the susceptibility to motion sickness. We used a visual motion paradigm with two conditions of the stimulated retinal field and the head posture to quantify postural stability while maintaining a static stance in 18 patients with vestibular migraine and in 13 age-matched healthy subjects. Three parameters of postural stability showed differences between VM patients and controls: RMS velocity (0.34 ± 0.02 cm/s vs. 0.28 ± 0.02 cm/s), RMS acceleration (8.94 ± 0.74 cm/s 2 vs. 6.69 ± 0.87 cm/s 2 ), and sway area (1.77 ± 0.22 cm 2 vs. 1.04 ± 0.25 cm 2 ). Patients with vestibular migraine showed marked postural instability of the head and neck when visual stimuli were presented in the retinal periphery. The pseudo-Coriolis effect induced by head roll tilt was not responsible for the main differences in postural instability between patients and controls. Patients with vestibular migraine showed a higher visual dependency and low stability of the postural control system when maintaining quiet standing, which may be related to susceptibility to motion sickness.

77 FR 31618 - Medicaid Program; Announcement of Requirements and Registration for CMS Provider Screening...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare & Medicaid Services (CMS) [CMS-2382-N... Challenge AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Notice. SUMMARY: The Centers for Medicare & Medicaid Services (CMS), is announcing the launch of the ``CMS Provider Screening...

Hydrodynamic Mediation of Killifish Predation on Infaunal Polychaetes

NASA Astrophysics Data System (ADS)

Hentschel, B. T.; Hayman, N. T.; Anderson, T. W.

2016-02-01

To explore predator-prey interactions between California killifish (Fundulus parvipinnis) and spionid polychaetes (Polydora cornuta and Streblospio benedicti) in tidal creeks, we conducted a laboratory flume experiment to quantify whether killifish prey-patch selectivity varies with flow speed. The flume included a 300-cm2 area of defaunated sediment within which we centrally positioned 24 P. cornuta, 24 S. benedicti, or no worms as a prey-free control. We videotaped groups of three killifish for 50 min at one of six unidirectional flow speeds (3, 6, 9, 12, 15, or 18 cm/s measured 1.5 cm above bottom) and recorded their bite rate anywhere in the sediment area vs. bites directed at the central prey patch (98 cm2). Each flow speed and prey treatment was replicated by four independent flume runs (i.e., 72 total flume runs). The percentage of bites directed at the central patch varied significantly with flow speed and worm presence. With defaunated sediment only, 33% of bites were directed at the central patch at all flow speeds, consistent with a null model of non-selective foraging. When either worm species inhabited the central patch, 65% of bites were directed at the central patch at 3 and 6 cm/s, and patch selectivity declined linearly as flow increased. Despite differences in morphology and behavior, the two prey species elicited similar foraging activity by killifish. We pooled the P. cornuta and S. benedicti treatments to determine the flow speed at which prey-patch selectivity by killifish became statistically indistinguishable from non-selective biting in the absence of prey. At flow speeds of 3, 6, and 9 cm/s, the percentage of bites located in the 98-cm2 patch was significantly greater when live worms were present compared to the prey-free controls. At 12, 15, and 18 cm/s, there was not a significant difference between the control patches and those containing live worms, indicating 12 cm/s is a flow threshold above which killifish cannot selectively forage on dense patches of infauna.

CS2 analysis in presence of non-Gaussian background noise - Effect on traditional estimators and resilience of log-envelope indicators

NASA Astrophysics Data System (ADS)

Borghesani, P.; Antoni, J.

2017-06-01

Second-order cyclostationary (CS2) analysis has become popular in the field of machine diagnostics and a series of digital signal processing techniques have been developed to extract CS2 components from the background noise. Among those techniques, squared envelope spectrum (SES) and cyclic modulation spectrum (CMS) have gained popularity thanks to their high computational efficiency and simple implementation. The effectiveness of CMS and SES has been previously quantified based on the hypothesis of Gaussian background noise and has led to statistical tests for the presence of CS2 peaks in squared envelope spectra and cyclic modulation spectra. However a recently established link of CMS with SES and of SES with kurtosis has exposed a potential weakness of those indicators in the case of highly leptokurtic background noise. This case is often present in practice when the machine is subjected to highly impulsive phenomena, either due to harsh operating conditions or to electric noise generated by power electronics and captured by the sensor. This study investigates and quantifies for the first time the effect of leptokurtic noise on the capabilities of SES and CMS, by analysing three progressively harsh situations: high kurtosis, infinite kurtosis and alpha-stable background noise (for which even first and second-order moments are not defined). Then the resilience of a recently proposed family of CS2 indicators, based on the log-envelope, is verified analytically, numerically and experimentally in the case of highly leptokurtic noise.

42 CFR 482.41 - Condition of participation: Physical environment.

Code of Federal Regulations, 2011 CFR

2011-10-01

... pharmaceutical, food preparation, and other appropriate areas. [51 FR 22042, June 17, 1986, as amended at 53 FR... rooms, and stairwells. In all other areas not serviced by the emergency supply source, battery lamps and.... 552(a) and 1 CFR part 51. A copy of the Code is available for inspection at the CMS Information...

42 CFR 482.41 - Condition of participation: Physical environment.

Code of Federal Regulations, 2012 CFR

2012-10-01

... pharmaceutical, food preparation, and other appropriate areas. [51 FR 22042, June 17, 1986, as amended at 53 FR... rooms, and stairwells. In all other areas not serviced by the emergency supply source, battery lamps and.... 552(a) and 1 CFR part 51. A copy of the Code is available for inspection at the CMS Information...

42 CFR 422.451 - Moratorium on new local preferred provider organization plans.

Code of Federal Regulations, 2010 CFR

2010-10-01

... for MA Regional Plans § 422.451 Moratorium on new local preferred provider organization plans. CMS... service area unless the MA organization seeking to offer the plan was offering a local preferred provider...

42 CFR 422.451 - Moratorium on new local preferred provider organization plans.

Code of Federal Regulations, 2011 CFR

2011-10-01

... for MA Regional Plans § 422.451 Moratorium on new local preferred provider organization plans. CMS... service area unless the MA organization seeking to offer the plan was offering a local preferred provider...

Brain glutamic acid decarboxylase-67kDa alterations induced by magnesium treatment in olfactory bulbectomy and chronic mild stress models in rats.

PubMed

Pochwat, Bartłomiej; Nowak, Gabriel; Szewczyk, Bernadeta

2016-10-01

The preclinical results indicate that magnesium, an N-methyl-d-aspartate receptor (NMDAR) blocker has anxiolytic and antidepressant-like activity. One of the mechanisms involved in these activities is modulation of glutamate, γ-aminobutyric acid (GABA) system. Based on this, the aim of the present study was to investigate the effect of magnesium on the level of glutamic acid decarboxylase-67kDa (GAD-67) in the different brain areas in the chronic mild stress (CMS) and olfactory bulbectomy (OB) models of depression in rats. Magnesium (15mg/kg) was administered intraperitonealy once daily for 14 days in the OB model and for 35 days in the CMS model. 24h after the last dose, the prefrontal cortex (PFC), hippocampus and amygdala were collected and the GAD-67 protein level was determined by the western blotting method. In the OB model, chronic magnesium treatment normalized decreased by OB protein level of GAD-67 in PFC. CMS did not influence the GAD-67 protein level, however magnesium increased GAD-67 protein expression in amygdala and PFC of stress rats when compared to vehicle-treated stress group. OB or CMS models as well as magnesium treatment did not affect GAD-67 protein level in the hippocampus. Obtained results indicate that the antidepressant-like activity of magnesium in CMS and OB models of depression is associated with an enhanced expression of GAD-67 in the PFC and amygdala. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Effects of functional feeds on the lipid composition, transcriptomic responses and pathology in heart of Atlantic salmon (Salmo salar L.) before and after experimental challenge with Piscine Myocarditis Virus (PMCV).

PubMed

Martinez-Rubio, Laura; Evensen, Øystein; Krasnov, Aleksei; Jørgensen, Sven Martin; Wadsworth, Simon; Ruohonen, Kari; Vecino, Jose L G; Tocher, Douglas R

2014-06-11

Cardiomyopathy syndrome (CMS) is a severe cardiac disease of Atlantic salmon (Salmo salar) recently associated with a double-stranded RNA virus, Piscine Myocarditis Virus (PMCV). The disease has been diagnosed in 75-85 farms in Norway each year over the last decade resulting in annual economic losses estimated at up to €9 million. Recently, we demonstrated that functional feeds led to a milder inflammatory response and reduced severity of heart lesions in salmon experimentally infected with Atlantic salmon reovirus, the causal agent of heart and skeletal muscle inflammation (HSMI). In the present study we employed a similar strategy to investigate the effects of functional feeds, with reduced lipid content and increased eicosapentaenoic acid levels, in controlling CMS in salmon after experimental infection with PMCV. Hepatic steatosis associated with CMS was significantly reduced over the time course of the infection in fish fed the functional feeds. Significant differences in immune and inflammatory responses and pathology in heart tissue were found in fish fed the different dietary treatments over the course of the infection. Specifically, fish fed the functional feeds showed a milder and delayed inflammatory response and, consequently, less severity of heart lesions at earlier and later stages after infection with PMCV. Decreasing levels of phosphatidylinositol in cell membranes combined with the increased expression of genes related with T-cell signalling pathways revealed new interactions between dietary lipid composition and the immune response in fish during viral infection. Dietary histidine supplementation did not significantly affect immune responses or levels of heart lesions. Combined with the previous findings on HSMI, the results of the present study highlight the potential role of clinical nutrition in controlling inflammatory diseases in Atlantic salmon. In particular, dietary lipid content and fatty acid composition may have important immune-modulatory effects in Atlantic salmon that could be potentially beneficial in fish balancing the immune and tissue responses to viral infections.

Combining data from high-energy pp-reactions and neutrinoless double-beta decay: Limits on the mass of the right-handed boson

NASA Astrophysics Data System (ADS)

Civitarese, Osvaldo; Suhonen, Jouni; Zuber, Kai

2016-10-01

From the recently established lower-limits on the nonobservability of the neutrinoless double-beta decay of 76Ge (GERDA collaboration) and 136Xe (EXO-200 and KamLAND-Zen collaborations), combined with the ATLAS and CMS data, we extract limits for the left-right (LR) mixing angle, ζ, of the SU(2)L ×SU(2)R electroweak Hamiltonian. For the theoretical analysis, which is a model dependent, we have adopted a minimal extension of the Standard Model (SM) of Electroweak Interactions belonging to the SU(2)L ×SU(2)R representation. The nuclear-structure input of the analysis consists of a set of matrix elements and phase-space factors, and the experimental lower-limits for the half-lives. The other input are the ATLAS and CMS cross-section measurements of the pp-collisions into two-jets and two-leptons, performed at the large hadron collider (LHC). Our analysis yields the limit ζ < 10-3 for MR > 3TeV, by combining the model-dependent limits extracted from the double-beta-decay measurements and those extracted from the results of the CMS and ATLAS measurements.

Study of inclusive single-jet production in the framework of kt-factorization unintegrated parton distributions

NASA Astrophysics Data System (ADS)

Aminzadeh Nik, R.; Modarres, M.; Masouminia, M. R.

2018-05-01

The present work is intended to study the double-differential cross section of the inclusive single-jet production as the functions of the transverse momentum and the rapidity of the jet in the high-energy hadron-hadron collisions. The angular-ordering-constraint kt-factorization framework is used to calculate the above cross section that is available experimentally. The conditions are taken in accordance with the LHC experiments. The results are compared and analyzed using the existing CMS LHC data. The scheme-dependent unintegrated parton distribution functions (UPDF) of Kimber-Martin-Ryskin (KMR) and Martin-Ryskin-Watt (MRW) in the leading-order and the next-to-leading order (NLO) are used to predict the input partonic UPDF. The utilized phenomenological frameworks prove to be relatively successful in generating satisfactory results compared to the different experiment data, such as CMS (8 and 13 TeV). Extensive discussions and comparisons are made regarding the behavior of the contributing partonic subprocesses. Finally, it is shown that the application of the KMR UPDF to the single-jet differential cross sections have better agreement with the CMS data; on the other hand, they are very similar to those of NLO-MRW.

Effect of ultrasonic stimulation on particle transport and fate over different lengths of porous media

NASA Astrophysics Data System (ADS)

Chen, Xingxin; Wu, Zhonghan; Cai, Qipeng; Cao, Wei

2018-04-01

It is well established that seismic waves traveling through porous media stimulate fluid flow and accelerate particle transport. However, the mechanism remains poorly understood. To quantify the coupling effect of hydrodynamic force, transportation distance, and ultrasonic stimulation on particle transport and fate in porous media, laboratory experiments were conducted using custom-built ultrasonic-controlled soil column equipment. Three column lengths (23 cm, 33 cm, and 43 cm) were selected to examine the influence of transportation distance. Transport experiments were performed with 0 W, 600 W, 1000 W, 1400 W, and 1800 W of applied ultrasound, and flow rates of 0.065 cm/s, 0.130 cm/s, and 0.195 cm/s, to establish the roles of ultrasonic stimulation and hydrodynamic force. The laboratory results suggest that whilst ultrasonic stimulation does inhibit suspended-particle deposition and accelerate deposited-particle release, both hydrodynamic force and transportation distance are the principal controlling factors. The median particle diameter for the peak concentration was approximately 50% of that retained in the soil column. Simulated particle-breakthrough curves using extended traditional filtration theory effectively described the experimental curves, particularly the curves that exhibited a higher tailing concentration.

42 CFR 493.1773 - Standard: Basic inspection requirements for all laboratories issued a CLIA certificate and CLIA...

Code of Federal Regulations, 2011 CFR

2011-10-01

... issued a certificate of accreditation, must permit CMS or a CMS agent to conduct validation and complaint inspections. (b) General requirements. As part of the inspection process, CMS or a CMS agent may require the... testing process (preanalytic, analytic, and postanalytic). (4) Permit CMS or a CMS agent access to all...

42 CFR 493.1773 - Standard: Basic inspection requirements for all laboratories issued a CLIA certificate and CLIA...

Code of Federal Regulations, 2012 CFR

2012-10-01

... issued a certificate of accreditation, must permit CMS or a CMS agent to conduct validation and complaint inspections. (b) General requirements. As part of the inspection process, CMS or a CMS agent may require the... testing process (preanalytic, analytic, and postanalytic). (4) Permit CMS or a CMS agent access to all...

42 CFR 493.1773 - Standard: Basic inspection requirements for all laboratories issued a CLIA certificate and CLIA...

Code of Federal Regulations, 2013 CFR

2013-10-01

... issued a certificate of accreditation, must permit CMS or a CMS agent to conduct validation and complaint inspections. (b) General requirements. As part of the inspection process, CMS or a CMS agent may require the... testing process (preanalytic, analytic, and postanalytic). (4) Permit CMS or a CMS agent access to all...

42 CFR 493.1773 - Standard: Basic inspection requirements for all laboratories issued a CLIA certificate and CLIA...

Code of Federal Regulations, 2014 CFR

2014-10-01

... issued a certificate of accreditation, must permit CMS or a CMS agent to conduct validation and complaint inspections. (b) General requirements. As part of the inspection process, CMS or a CMS agent may require the... testing process (preanalytic, analytic, and postanalytic). (4) Permit CMS or a CMS agent access to all...

42 CFR 493.1773 - Standard: Basic inspection requirements for all laboratories issued a CLIA certificate and CLIA...

Code of Federal Regulations, 2010 CFR

2010-10-01

... issued a certificate of accreditation, must permit CMS or a CMS agent to conduct validation and complaint inspections. (b) General requirements. As part of the inspection process, CMS or a CMS agent may require the... testing process (preanalytic, analytic, and postanalytic). (4) Permit CMS or a CMS agent access to all...

Standard duplex criteria overestimate the degree of stenosis after eversion carotid endarterectomy.

PubMed

Benzing, Travis; Wilhoit, Cameron; Wright, Sharee; McCann, P Aaron; Lessner, Susan; Brothers, Thomas E

2015-06-01

The eversion technique for carotid endarterectomy (eCEA) offers an alternative to longitudinal arteriotomy and patch closure (pCEA) for open carotid revascularization. In some reports, eCEA has been associated with a higher rate of >50% restenosis of the internal carotid when it is defined as peak systolic velocity (PSV) >125 cm/s by duplex imaging. Because the conformation of the carotid bifurcation may differ after eCEA compared with native carotid arteries, it was hypothesized that standard duplex criteria might not accurately reflect the presence of restenosis after eCEA. In a case-control study, the outcomes of all patients undergoing carotid endarterectomy by one surgeon during the last 10 years were analyzed retrospectively, with a primary end point of PSV >125 cm/s. Duplex flow velocities were compared with luminal diameter measurements for any carotid computed tomography arteriography or magnetic resonance angiography study obtained within 2 months of duplex imaging, with the degree of stenosis calculated by the methodology used in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST) as well as cross-sectional area (CSA) reduction. Simulations were generated and analyzed by computational model simulations of the eCEA and pCEA arteries. Eversion and longitudinal arteriotomy with patch techniques were used in 118 and 177 carotid arteries, respectively. Duplex follow-up was available in 90 eCEA arteries at a median of 16 (range, 2-136) months and in 150 pCEA arteries at a median of 41 (range, 3-115) months postoperatively. PSV >125 cm/s was present at some time during follow-up in 31% of eCEA and pCEA carotid arteries, each, and in the most recent duplex examination in 7% after eCEA and 21% after pCEA (P = .003), with no eCEA and two pCEA arteries occluding completely during follow-up (P = .29). In 19 carotid arteries with PSV >125 cm/s after angle correction (median, 160 cm/s; interquartile range, 146-432 cm/s) after eCEA that were subsequently examined by axial imaging, the mean percentage stenosis was 8% ± 11% by NASCET, 11% ± 5% by ECST, and 20% ± 9% by CSA criteria. For eight pCEA arteries with PSV >125 cm/s (median velocity, 148 cm/s; interquartile range, 139-242 cm/s), the corresponding NASCET, ECST, and CSA stenoses were 8% ± 35%, 26% ± 32%, and 25% ± 33%, respectively. NASCET internal carotid diameter reduction of at least 50% was noted by axial imaging after two of the eight pCEAs, and the PSV exceeded 200 cm/s in each case. The presence of hemodynamically significant carotid artery restenosis may be overestimated by standard duplex criteria after eCEA and perhaps after pCEA. Insufficient information currently exists to determine what PSV does correspond to hemodynamically significant restenosis. Published by Elsevier Inc.

Solving a mathematical model integrating unequal-area facilities layout and part scheduling in a cellular manufacturing system by a genetic algorithm.

PubMed

Ebrahimi, Ahmad; Kia, Reza; Komijan, Alireza Rashidi

2016-01-01

In this article, a novel integrated mixed-integer nonlinear programming model is presented for designing a cellular manufacturing system (CMS) considering machine layout and part scheduling problems simultaneously as interrelated decisions. The integrated CMS model is formulated to incorporate several design features including part due date, material handling time, operation sequence, processing time, an intra-cell layout of unequal-area facilities, and part scheduling. The objective function is to minimize makespan, tardiness penalties, and material handling costs of inter-cell and intra-cell movements. Two numerical examples are solved by the Lingo software to illustrate the results obtained by the incorporated features. In order to assess the effects and importance of integration of machine layout and part scheduling in designing a CMS, two approaches, sequentially and concurrent are investigated and the improvement resulted from a concurrent approach is revealed. Also, due to the NP-hardness of the integrated model, an efficient genetic algorithm is designed. As a consequence, computational results of this study indicate that the best solutions found by GA are better than the solutions found by B&B in much less time for both sequential and concurrent approaches. Moreover, the comparisons between the objective function values (OFVs) obtained by sequential and concurrent approaches demonstrate that the OFV improvement is averagely around 17 % by GA and 14 % by B&B.

Effects of intravenous bolus injection of nicorandil on renal artery flow velocity assessed by color Doppler ultrasound.

PubMed

Shimamoto, Yukiko; Kubo, Takashi; Tanabe, Kazumi; Emori, Hiroki; Katayama, Yosuke; Nishiguchi, Tsuyoshi; Taruya, Akira; Kameyama, Takeyoshi; Orii, Makoto; Yamano, Takashi; Kuroi, Akio; Yamaguchi, Tomoyuki; Takemoto, Kazushi; Matsuo, Yoshiki; Ino, Yasushi; Tanaka, Atsushi; Hozumi, Takeshi; Terada, Masaki; Akasaka, Takashi

2017-01-01

Previous animal studies have shown that a potassium channel opener, nicorandil, provokes vasodilation in renal microvasculature and increases renal blood flow. We conducted a clinical study that aimed to evaluate the effect of nicorandil on renal artery blood flow in comparison with nitroglycerin by using color Doppler ultrasound. The present study enrolled 40 patients with stable coronary artery disease who had no renal arterial stenosis and renal parenchymal disease. The patients received intravenous administration of nicorandil (n=20) or nitroglycerin (n=20). Before and after the administration, renal artery blood flow velocity was measured by color-guided pulsed-wave Doppler. The peak-systolic, end-diastolic, and mean renal artery blood flow velocities before the administration were not different between the nicorandil group and the nitroglycerin group. The peak-systolic (79±15cm/s to 99±21cm/s, p<0.001; and 78±19cm/s to 85±19cm/s, p=0.004), end-diastolic (22±5cm/s to 28±8cm/s, p<0.001; and 24±6cm/s to 26±6cm/s, p=0.005) and mean (41±6cm/s to 49±9cm/s, p<0.001; and 43±9cm/s to 45±9cm/s, p=0.009) renal artery flow velocities increased significantly in either group. The nominal changes in the peak-systolic (20±10cm/s vs. 7±8cm/s, p<0.001), end-diastolic (5±4cm/s vs. 2±3cm/s, p=0.001), and mean (8±5cm/s vs. 2±2cm/s, p<0.001) renal artery blood flow velocities were significantly greater in the nicorandil group compared with the nitroglycerin group. Intravenous nicorandil increased renal artery blood flow velocity in comparison with nitroglycerin. Nicorandil has a significant effect on renal hemodynamics. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Altered iPSC-derived neurons’ sodium channel properties in subjects with Monge's disease

PubMed Central

Zhao, Huiwen W.; Gu, Xiang Q.; Chailangkarn, Thanathom; Perkins, Guy; Callacondo, David; Appenzeller, Otto; Poulsen, Orit; Zhou, Dan; Muotri, Alysson R.; Haddad, Gabriel G.

2015-01-01

Monge's disease, also known as chronic mountain sickness (CMS), is a disease that potentially threatens more than 140 million highlanders during extended time living at a high altitude (over 2500m). The prevalence of CMS in Andeans is about 15-20%, suggesting that the majority of highlanders (non-CMS) are rather healthy at the high altitude; however, CMS subjects experience severe hypoxemia, erythrocytosis and many neurologic manifestations including migraine, headache, mental fatigue, confusion, and memory loss. The underlying mechanisms of CMS neuropathology are not well understood and no ideal treatment is available to prevent or cure CMS, except for phlebotomy. In the current study, we reprogrammed fibroblast cells from both CMS and non-CMS subjects’ skin biopsies into the induced pluripotent stem cells (iPSCs), then differentiated into neurons and compared their neuronal properties. We discovered that CMS neurons were much less excitable (higher rheobase) than non-CMS neurons. This decreased excitability was not caused by differences in passive neuronal properties, but instead by a significantly lowered Na+ channel current density and by a shift of the voltage-conductance curve in the depolarization direction. Our findings provide, for the first time, evidence of a neuronal abnormality in CMS subjects as compared to non-CMS subjects, hoping that such studies can pave the way to a better understanding of the neuropathology in CMS. PMID:25559931

Geologic implications and potential hazards of scour depressions on bering shelf, Alaska

USGS Publications Warehouse

Larsen, M.C.; Nelson, H.; Thor, D.R.

1979-01-01

Flat-bottomed depression 50-150 m in diameter and 60-80 cm deep occur in the floor of Norton Sound, Bering Sea. These large erosional bedforms and associated current ripples are found in areas where sediment grain size is 0.063-0.044 mm (4-4.5 ??), speeds of bottom currents are greatest (20-30 cm/s mean speeds under nonstorm conditions, 70 cm/s during typical storms), circulation of water is constricted by major topographic shoals (kilometers in scale), and small-scale topographic disruptions, such as ice gouges, occur locally on slopes of shoals. These local obstructions on shoals appear to disrupt currents, causing separation of flow and generating eddies that produce large-scale scour. Offshore artificial structures also may disrupt bottom currents in these same areas and have the potential to generate turbulence and induce extensive scour in the area of disrupted flow. The size and character of natural scour depressions in areas of ice gouging suggest that large-scale regions of scour may develop from enlargement of local scour sites around pilings, platforms, or pipelines. Consequently, loss of substrate support for pipelines and gravity structures is possible during frequent autumn storms. ?? 1979 Springer-Verlag New York Inc.

Fabrication of fibrillized collagen microspheres with the microstructure resembling an extracellular matrix.

PubMed

Matsuhashi, Aki; Nam, Kwangwoo; Kimura, Tsuyoshi; Kishida, Akio

2015-04-14

Microspheres using artificial or natural materials have been widely applied in the field of tissue engineering and drug delivery systems. Collagen is being widely used for microspheres because of its abundancy in the extracellular matrix (ECM), and its good biocompatibility. The purpose of this study is to establish the appropriate condition for preparing collagen microspheres (CMS) and fibrillized collagen microspheres (fCMS) using water-in-oil (W/O) emulsion. Collagen can be tailored to mimic the native cell environment possessing a similar microstructure to that of the ECM by conditioning the aqueous solution. We focused on the preparation of stable and injectable CMS and fCMS which is stable and would promote the healing response. Controlling the interfacial properties of hydrophilic-lipophilic balance (HLB), we obtained CMS and fCMS with various sizes and various morphologies. The microsphere prepared with wetting agents showed good microsphere formation, but too low or too high HLB value caused low yield and uncontrollable size distribution. The change in the surfactant amount and the rotor speed also affected the formation of the CMS and fCMS, where the low surfactant amount and fast rotor speed produced smaller CMS and fCMS. In the case of fCMS, the presence of NaCl made it possible to prepare stable fCMS without using any cross-linker due to fibrillogenesis and gelling of collagen molecules. The microstructure of fCMS was similar to that of the native tissue indicating that the fCMS would replicate its function in vivo.

Successfully Preparing Your CMS Web Area for OWC Review

EPA Pesticide Factsheets

Common issues in draft websites reviewed by EPA's Office of Web Communications that result in multiple rounds of review; such as lack of focus on key audiences' top tasks, not using plain language and conciseness, and unclear titles and headings.

Penetration, Completeness, and Representativeness of The Society of Thoracic Surgeons Adult Cardiac Surgery Database.

PubMed

Jacobs, Jeffrey P; Shahian, David M; He, Xia; O'Brien, Sean M; Badhwar, Vinay; Cleveland, Joseph C; Furnary, Anthony P; Magee, Mitchell J; Kurlansky, Paul A; Rankin, J Scott; Welke, Karl F; Filardo, Giovanni; Dokholyan, Rachel S; Peterson, Eric D; Brennan, J Matthew; Han, Jane M; McDonald, Donna; Schmitz, DeLaine; Edwards, Fred H; Prager, Richard L; Grover, Frederick L

2016-01-01

The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) has been successfully linked to the Centers for Medicare and Medicaid (CMS) Medicare database, thereby facilitating comparative effectiveness research and providing information about long-term follow-up and cost. The present study uses this link to determine contemporary completeness, penetration, and representativeness of the STS ACSD. Using variables common to both STS and CMS databases, STS operations were linked to CMS data for all CMS coronary artery bypass graft (CABG) surgery hospitalizations discharged between 2000 and 2012, inclusive. For each CMS CABG hospitalization, it was determined whether a matching STS record existed. Center-level penetration (number of CMS sites with at least one matched STS participant divided by the total number of CMS CABG sites) increased from 45% in 2000 to 90% in 2012. In 2012, 973 of 1,081 CMS CABG sites (90%) were linked to an STS site. Patient-level penetration (number of CMS CABG hospitalizations done at STS sites divided by the total number of CMS CABG hospitalizations) increased from 51% in 2000 to 94% in 2012. In 2012, 71,634 of 76,072 CMS CABG hospitalizations (94%) occurred at an STS site. Completeness of case inclusion at STS sites (number of CMS CABG cases at STS sites linked to STS records divided by the total number of CMS CABG cases at STS sites) increased from 88% in 2000 to 98% in 2012. In 2012, 69,213 of 70,932 CMS CABG hospitalizations at STS sites (98%) were linked to an STS record. Linkage of STS and CMS databases demonstrates high and increasing penetration and completeness of the STS database. Linking STS and CMS data facilitates studying long-term outcomes and costs of cardiothoracic surgery. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Correlation between human ether‐a‐go‐go‐related gene channel inhibition and action potential prolongation

PubMed Central

Saxena, P; Hortigon‐Vinagre, M P; Beyl, S; Baburin, I; Andranovits, S; Iqbal, S M; Costa, A; IJzerman, A P; Kügler, P; Timin, E

2017-01-01

Background and Purpose Human ether‐a‐go‐go‐related gene (hERG; Kv11.1) channel inhibition is a widely accepted predictor of cardiac arrhythmia. hERG channel inhibition alone is often insufficient to predict pro‐arrhythmic drug effects. This study used a library of dofetilide derivatives to investigate the relationship between standard measures of hERG current block in an expression system and changes in action potential duration (APD) in human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs). The interference from accompanying block of Cav1.2 and Nav1.5 channels was investigated along with an in silico AP model. Experimental Approach Drug‐induced changes in APD were assessed in hiPSC‐CMs using voltage‐sensitive dyes. The IC50 values for dofetilide and 13 derivatives on hERG current were estimated in an HEK293 expression system. The relative potency of each drug on APD was estimated by calculating the dose (D150) required to prolong the APD at 90% (APD90) repolarization by 50%. Key Results The D150 in hiPSC‐CMs was linearly correlated with IC50 of hERG current. In silico simulations supported this finding. Three derivatives inhibited hERG without prolonging APD, and these compounds also inhibited Cav1.2 and/or Nav1.5 in a channel state‐dependent manner. Adding Cav1.2 and Nav1.2 block to the in silico model recapitulated the direction but not the extent of the APD change. Conclusions and Implications Potency of hERG current inhibition correlates linearly with an index of APD in hiPSC‐CMs. The compounds that do not correlate have additional effects including concomitant block of Cav1.2 and/or Nav1.5 channels. In silico simulations of hiPSC‐CMs APs confirm the principle of the multiple ion channel effects. PMID:28681507

CMS Analysis and Data Reduction with Apache Spark

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

Gutsche, Oliver; Canali, Luca; Cremer, Illia

Experimental Particle Physics has been at the forefront of analyzing the world's largest datasets for decades. The HEP community was among the first to develop suitable software and computing tools for this task. In recent times, new toolkits and systems for distributed data processing, collectively called "Big Data" technologies have emerged from industry and open source projects to support the analysis of Petabyte and Exabyte datasets in industry. While the principles of data analysis in HEP have not changed (filtering and transforming experiment-specific data formats), these new technologies use different approaches and tools, promising a fresh look at analysis ofmore » very large datasets that could potentially reduce the time-to-physics with increased interactivity. Moreover these new tools are typically actively developed by large communities, often profiting of industry resources, and under open source licensing. These factors result in a boost for adoption and maturity of the tools and for the communities supporting them, at the same time helping in reducing the cost of ownership for the end-users. In this talk, we are presenting studies of using Apache Spark for end user data analysis. We are studying the HEP analysis workflow separated into two thrusts: the reduction of centrally produced experiment datasets and the end-analysis up to the publication plot. Studying the first thrust, CMS is working together with CERN openlab and Intel on the CMS Big Data Reduction Facility. The goal is to reduce 1 PB of official CMS data to 1 TB of ntuple output for analysis. We are presenting the progress of this 2-year project with first results of scaling up Spark-based HEP analysis. Studying the second thrust, we are presenting studies on using Apache Spark for a CMS Dark Matter physics search, comparing Spark's feasibility, usability and performance to the ROOT-based analysis.« less

A Universal and Robust Integrated Platform for the Scalable Production of Human Cardiomyocytes From Pluripotent Stem Cells.

PubMed

Fonoudi, Hananeh; Ansari, Hassan; Abbasalizadeh, Saeed; Larijani, Mehran Rezaei; Kiani, Sahar; Hashemizadeh, Shiva; Zarchi, Ali Sharifi; Bosman, Alexis; Blue, Gillian M; Pahlavan, Sara; Perry, Matthew; Orr, Yishay; Mayorchak, Yaroslav; Vandenberg, Jamie; Talkhabi, Mahmood; Winlaw, David S; Harvey, Richard P; Aghdami, Nasser; Baharvand, Hossein

2015-12-01

Recent advances in the generation of cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs), in conjunction with the promising outcomes from preclinical and clinical studies, have raised new hopes for cardiac cell therapy. We report the development of a scalable, robust, and integrated differentiation platform for large-scale production of hPSC-CM aggregates in a stirred suspension bioreactor as a single-unit operation. Precise modulation of the differentiation process by small molecule activation of WNT signaling, followed by inactivation of transforming growth factor-β and WNT signaling and activation of sonic hedgehog signaling in hPSCs as size-controlled aggregates led to the generation of approximately 100% beating CM spheroids containing virtually pure (∼90%) CMs in 10 days. Moreover, the developed differentiation strategy was universal, as demonstrated by testing multiple hPSC lines (5 human embryonic stem cell and 4 human inducible PSC lines) without cell sorting or selection. The produced hPSC-CMs successfully expressed canonical lineage-specific markers and showed high functionality, as demonstrated by microelectrode array and electrophysiology tests. This robust and universal platform could become a valuable tool for the mass production of functional hPSC-CMs as a prerequisite for realizing their promising potential for therapeutic and industrial applications, including drug discovery and toxicity assays. Recent advances in the generation of cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs) and the development of novel cell therapy strategies using hPSC-CMs (e.g., cardiac patches) in conjunction with promising preclinical and clinical studies, have raised new hopes for patients with end-stage cardiovascular disease, which remains the leading cause of morbidity and mortality globally. In this study, a simplified, scalable, robust, and integrated differentiation platform was developed to generate clinical grade hPSC-CMs as cell aggregates under chemically defined culture conditions. This approach resulted in approximately 100% beating CM spheroids with virtually pure (∼90%) functional cardiomyocytes in 10 days from multiple hPSC lines. This universal and robust bioprocessing platform can provide sufficient numbers of hPSC-CMs for companies developing regenerative medicine technologies to rescue, replace, and help repair damaged heart tissues and for pharmaceutical companies developing advanced biologics and drugs for regeneration of lost heart tissue using high-throughput technologies. It is believed that this technology can expedite clinical progress in these areas to achieve a meaningful impact on improving clinical outcomes, cost of care, and quality of life for those patients disabled and experiencing heart disease. ©AlphaMed Press.

A Universal and Robust Integrated Platform for the Scalable Production of Human Cardiomyocytes From Pluripotent Stem Cells

PubMed Central

Fonoudi, Hananeh; Ansari, Hassan; Abbasalizadeh, Saeed; Larijani, Mehran Rezaei; Kiani, Sahar; Hashemizadeh, Shiva; Zarchi, Ali Sharifi; Bosman, Alexis; Blue, Gillian M.; Pahlavan, Sara; Perry, Matthew; Orr, Yishay; Mayorchak, Yaroslav; Vandenberg, Jamie; Talkhabi, Mahmood; Winlaw, David S.; Harvey, Richard P.; Aghdami, Nasser

2015-01-01

Recent advances in the generation of cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs), in conjunction with the promising outcomes from preclinical and clinical studies, have raised new hopes for cardiac cell therapy. We report the development of a scalable, robust, and integrated differentiation platform for large-scale production of hPSC-CM aggregates in a stirred suspension bioreactor as a single-unit operation. Precise modulation of the differentiation process by small molecule activation of WNT signaling, followed by inactivation of transforming growth factor-β and WNT signaling and activation of sonic hedgehog signaling in hPSCs as size-controlled aggregates led to the generation of approximately 100% beating CM spheroids containing virtually pure (∼90%) CMs in 10 days. Moreover, the developed differentiation strategy was universal, as demonstrated by testing multiple hPSC lines (5 human embryonic stem cell and 4 human inducible PSC lines) without cell sorting or selection. The produced hPSC-CMs successfully expressed canonical lineage-specific markers and showed high functionality, as demonstrated by microelectrode array and electrophysiology tests. This robust and universal platform could become a valuable tool for the mass production of functional hPSC-CMs as a prerequisite for realizing their promising potential for therapeutic and industrial applications, including drug discovery and toxicity assays. Significance Recent advances in the generation of cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs) and the development of novel cell therapy strategies using hPSC-CMs (e.g., cardiac patches) in conjunction with promising preclinical and clinical studies, have raised new hopes for patients with end-stage cardiovascular disease, which remains the leading cause of morbidity and mortality globally. In this study, a simplified, scalable, robust, and integrated differentiation platform was developed to generate clinical grade hPSC-CMs as cell aggregates under chemically defined culture conditions. This approach resulted in approximately 100% beating CM spheroids with virtually pure (∼90%) functional cardiomyocytes in 10 days from multiple hPSC lines. This universal and robust bioprocessing platform can provide sufficient numbers of hPSC-CMs for companies developing regenerative medicine technologies to rescue, replace, and help repair damaged heart tissues and for pharmaceutical companies developing advanced biologics and drugs for regeneration of lost heart tissue using high-throughput technologies. It is believed that this technology can expedite clinical progress in these areas to achieve a meaningful impact on improving clinical outcomes, cost of care, and quality of life for those patients disabled and experiencing heart disease. PMID:26511653

Stress alters asenapine-induced Fos expression in the Meynert's nucleus: response of adjacent hypocretin and melanin-concentrating hormone neurons in rat.

PubMed

Majercikova, Z; Kiss, A

2016-01-01

Asenapine (ASE), an atypical antipsychotic drug used in the treatment of schizophrenia, induces Fos expression in forebrain. Effect of ASE on activity of basal nucleus of Meynert (NBM) cells, a part of the striatal-cortical circuits, was studied. We were also interested to reveal whether a chronic unpredictable variable mild stress (CMS) preconditioning might affect the ASE impact. Rats were divided into as follows: controls-vehicle, controls-ASE, stressed-vehicle and stressed-ASE groups. CMS included restrain, social isolation, crowding, swimming and cold applied for 21 days. On the 22nd day, rats were subcutaneously injected with ASE (0.3 mg/kg) or vehicle (saline 300 μl/rat), 90 min prior euthanizing. After transcardial fixation, brains were cut into 30 μm thick coronal sections. Fos protein presence, as indicator of cell activity, was detected by ABC immunohistochemistry. Hypocretin (Hcrt) and melanin-concentrating hormone (MCH) containing cells were visualized with fluorescent dyes. ASE induced significant increase in Fos expression in NBM in both controls and CMS preconditioned rats in comparison with the related vehicle-treated controls. CMS preconditioning, however, significantly lowered the Fos response to ASE in NBM. From Hrct and MCH cells, only Hcrt ones displayed Fos presence in response to ASE. This study demonstrates for the first time that ASE may target a special group of cells occupying NBM, which effect can be modulated by CMS preconditioning. This finding extends a view that ASE impact may extend beyond the classical forebrain target areas common for the action of all antipsychotics and might be helpful in the identification of sites and side effects of its therapeutic actions.

Perceptions, opinions and knowledge of pharmacists towards the use of complementary medicines by people living with cancer.

PubMed

Harnett, Joanna; Le, Trong Quy; Smith, Lorraine; Krass, Ines

2018-05-09

Background Biologically-based complementary medicine (BB-CM) use is prevalent amongst people living with cancer. Pharmacists play an important role in the provision of standard treatments for cancer. Less is known about pharmacist's provision of BB-CM information. Objective This study investigated the opinions, perceptions and knowledge of pharmacists regarding the use of BB-CMs by people living with cancer and the facilitators and barriers to providing information and advice. Setting Australia. Method A cross-sectional 53-item survey was developed and the survey link distributed in two professional associations newsletters. The associations represent ~29,000 pharmacists. Questions were categories into pharmacist's perceptions, opinions, and knowledge towards the use of BB-CM in cancer. Main Outcome Measure Scores obtained from responses to perception, opinion and knowledge statements and responses to demographic questions Results Respondents (n=70) were predominantly female (73%), Caucasian (66%) and under 40 years of age (78%). Respondents estimated that 19% of daily inquiries related to BB-CMs. Seventy-two per cent of respondents believed they had a responsibility to advise about the concomitant use of BB-CM with standard cancer treatments despite 60% reporting a lack of confidence in their knowledge. There was a moderate positive association (Spearman's rho 0.41 p= 0.001) between a pharmacists confidence in their level of knowledge and their total knowledge scores. The main barriers to providing information about BB-CMs reported were inadequate training in BB-CMs (94%) and reservations about the evidence base for efficacy and safety (50%). Conclusion Pharmacists have a role to play in counselling people living with cancer about their use of BB-CMs and this role could be maximized with further training and education in this area.

Increased vulnerability to depressive-like behavior of mice with decreased expression of VGLUT1.

PubMed

Garcia-Garcia, Alvaro L; Elizalde, Natalia; Matrov, Denis; Harro, Jaanus; Wojcik, Sonja M; Venzala, Elisabet; Ramírez, Maria J; Del Rio, Joaquin; Tordera, Rosa M

2009-08-01

Many studies link depression to an increase in the excitatory-inhibitory ratio in the forebrain. Presynaptic alterations in a shared pathway of the glutamate/gamma-aminobutyric acid (GABA) cycle may account for this imbalance. Evidence suggests that decreased vesicular glutamate transporter 1 (VGLUT1) levels in the forebrain affect the glutamate/GABA cycle and induce helpless behavior. We studied decreased VGLUT1 as a potential factor enhancing a depressive-like phenotype in an animal model. Glutamate and GABA synthesis as well as oxidative metabolism were studied in heterozygous mice for the VGLUT1+/- and wildtype. The regulation of neurotransmitter levels, proteins involved in the glutamate/GABA cycle, and behavior by both genotype and chronic mild stress (CMS) were studied. Finally, the effect of chronic imipramine on VGLUT1 control and CMS mice was studied. VGLUT1+/- mice showed increased neuronal synthesis of glutamate; decreased cortical and hippocampal GABA, VGLUT1, and excitatory amino acid transporter 1 (EAAT1) as well as helplessness and anhedonia. CMS induced an increase of glutamate and a decrease of GABA, the vesicular GABA transporter (VGAT), and glutamic acid decarboxylase 65 (GAD65) in both areas and led to upregulation of EAAT1 in the hippocampus. Moreover, CMS induced anhedonia, helplessness, anxiety, and impaired recognition memory. VGLUT1+/- CMS mice showed a combined phenotype (genotype plus stress) and specific alterations, such as an upregulation of VGLUT2 and hyperlocomotion. Moreover, an increased vulnerability to anhedonia and helplessness reversible by chronic imipramine was shown. These studies highlight a crucial role for decreased VGLUT1 in the forebrain as a biological mediator of increased vulnerability to chronic mild stress.

78 FR 38986 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-28

... that information was collected under Part B. The QIMS Account Registration and the ESRD Application..., CMS-1728-94, CMS-10174, CMS-10305 and CMS-10488] Agency Information Collection Activities: Proposed... comment on CMS' intention to collect information from the public. Under the Paperwork Reduction Act of...

42 CFR 482.74 - Condition of participation: Notification to CMS.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Condition of participation: Notification to CMS... participation: Notification to CMS. (a) A transplant center must notify CMS immediately of any significant... conditions of participation. Instances in which CMS should receive information for follow up, as appropriate...

Perceptions, use and attitudes of pharmacy customers on complementary medicines and pharmacy practice.

PubMed

Braun, Lesley A; Tiralongo, Evelin; Wilkinson, Jenny M; Spitzer, Ondine; Bailey, Michael; Poole, Susan; Dooley, Michael

2010-07-20

Complementary medicines (CMs) are popular amongst Australians and community pharmacy is a major supplier of these products. This study explores pharmacy customer use, attitudes and perceptions of complementary medicines, and their expectations of pharmacists as they relate to these products. Pharmacy customers randomly selected from sixty large and small, metropolitan and rural pharmacies in three Australian states completed an anonymous, self administered questionnaire that had been pre-tested and validated. 1,121 customers participated (response rate 62%). 72% had used CMs within the previous 12 months, 61% used prescription medicines daily and 43% had used both concomitantly. Multivitamins, fish oils, vitamin C, glucosamine and probiotics were the five most popular CMs. 72% of people using CMs rated their products as 'very effective' or 'effective enough'. CMs were as frequently used by customers aged 60 years or older as younger customers (69% vs. 72%) although the pattern of use shifted with older age. Most customers (92%) thought pharmacists should provide safety information about CMs, 90% thought they should routinely check for interactions, 87% thought they should recommend effective CMs, 78% thought CMs should be recorded in customer's medication profile and 58% thought pharmacies stocking CMs should also employ a complementary medicine practitioner. Of those using CMs, 93% thought it important for pharmacists to be knowledgeable about CMs and 48% felt their pharmacist provides useful information about CMs. CMs are widely used by pharmacy customers of all ages who want pharmacists to be more involved in providing advice about these products.

Recombination Events Involving the atp9 Gene Are Associated with Male Sterility of CMS PET2 in Sunflower.

PubMed

Reddemann, Antje; Horn, Renate

2018-03-11

Cytoplasmic male sterility (CMS) systems represent ideal mutants to study the role of mitochondria in pollen development. In sunflower, CMS PET2 also has the potential to become an alternative CMS source for commercial sunflower hybrid breeding. CMS PET2 originates from an interspecific cross of H. petiolaris and H. annuus as CMS PET1, but results in a different CMS mechanism. Southern analyses revealed differences for atp6 , atp9 and cob between CMS PET2, CMS PET1 and the male-fertile line HA89. A second identical copy of atp6 was present on an additional CMS PET2-specific fragment. In addition, the atp9 gene was duplicated. However, this duplication was followed by an insertion of 271 bp of unknown origin in the 5' coding region of the atp9 gene in CMS PET2, which led to the creation of two unique open reading frames orf288 and orf231 . The first 53 bp of orf288 are identical to the 5' end of atp9 . Orf231 consists apart from the first 3 bp, being part of the 271-bp-insertion, of the last 228 bp of atp9 . These CMS PET2-specific orfs are co-transcribed. All 11 editing sites of the atp9 gene present in orf231 are fully edited. The anther-specific reduction of the co-transcript in fertility-restored hybrids supports the involvement in male-sterility based on CMS PET2.

Enhanced balance associated with coordination training with stochastic resonance stimulation in subjects with functional ankle instability: an experimental trial.

PubMed

Ross, Scott E; Arnold, Brent L; Blackburn, J Troy; Brown, Cathleen N; Guskiewicz, Kevin M

2007-12-17

Ankle sprains are common injuries that often lead to functional ankle instability (FAI), which is a pathology defined by sensations of instability at the ankle and recurrent ankle sprain injury. Poor postural stability has been associated with FAI, and sports medicine clinicians rehabilitate balance deficits to prevent ankle sprains. Subsensory electrical noise known as stochastic resonance (SR) stimulation has been used in conjunction with coordination training to improve dynamic postural instabilities associated with FAI. However, unlike static postural deficits, dynamic impairments have not been indicative of ankle sprain injury. Therefore, the purpose of this study was to examine the effects of coordination training with or without SR stimulation on static postural stability. Improving postural instabilities associated with FAI has implications for increasing ankle joint stability and decreasing recurrent ankle sprains. This study was conducted in a research laboratory. Thirty subjects with FAI were randomly assigned to either a: 1) conventional coordination training group (CCT); 2) SR stimulation coordination training group (SCT); or 3) control group. Training groups performed coordination exercises for six weeks. The SCT group received SR stimulation during training, while the CCT group only performed coordination training. Single leg postural stability was measured after the completion of balance training. Static postural stability was quantified on a force plate using anterior/posterior (A/P) and medial/lateral (M/L) center-of-pressure velocity (COPvel), M/L COP standard deviation (COPsd), M/L COP maximum excursion (COPmax), and COP area (COParea). Treatment effects comparing posttest to pretest COP measures were highest for the SCT group. At posttest, the SCT group had reduced A/P COPvel (2.3 +/- 0.4 cm/s vs. 2.7 +/- 0.6 cm/s), M/L COPvel (2.6 +/- 0.5 cm/s vs. 2.9 +/- 0.5 cm/s), M/L COPsd (0.63 +/- 0.12 cm vs. 0.73 +/- 0.11 cm), M/L COPmax (1.76 +/- 0.25 cm vs. 1.98 +/- 0.25 cm), and COParea (0.13 +/- 0.03 cm2 vs. 0.16 +/- 0.04 cm2) than the pooled means of the CCT and control groups (P < 0.05). Reduced values in COP measures indicated postural stability improvements. Thus, six weeks of coordination training with SR stimulation enhanced postural stability. Future research should examine the use of SR stimulation for decreasing recurrent ankle sprain injury in physically active individuals with FAI.

Enhanced balance associated with coordination training with stochastic resonance stimulation in subjects with functional ankle instability: an experimental trial

PubMed Central

Ross, Scott E; Arnold, Brent L; Blackburn, J Troy; Brown, Cathleen N; Guskiewicz, Kevin M

2007-01-01

Background Ankle sprains are common injuries that often lead to functional ankle instability (FAI), which is a pathology defined by sensations of instability at the ankle and recurrent ankle sprain injury. Poor postural stability has been associated with FAI, and sports medicine clinicians rehabilitate balance deficits to prevent ankle sprains. Subsensory electrical noise known as stochastic resonance (SR) stimulation has been used in conjunction with coordination training to improve dynamic postural instabilities associated with FAI. However, unlike static postural deficits, dynamic impairments have not been indicative of ankle sprain injury. Therefore, the purpose of this study was to examine the effects of coordination training with or without SR stimulation on static postural stability. Improving postural instabilities associated with FAI has implications for increasing ankle joint stability and decreasing recurrent ankle sprains. Methods This study was conducted in a research laboratory. Thirty subjects with FAI were randomly assigned to either a: 1) conventional coordination training group (CCT); 2) SR stimulation coordination training group (SCT); or 3) control group. Training groups performed coordination exercises for six weeks. The SCT group received SR stimulation during training, while the CCT group only performed coordination training. Single leg postural stability was measured after the completion of balance training. Static postural stability was quantified on a force plate using anterior/posterior (A/P) and medial/lateral (M/L) center-of-pressure velocity (COPvel), M/L COP standard deviation (COPsd), M/L COP maximum excursion (COPmax), and COP area (COParea). Results Treatment effects comparing posttest to pretest COP measures were highest for the SCT group. At posttest, the SCT group had reduced A/P COPvel (2.3 ± 0.4 cm/s vs. 2.7 ± 0.6 cm/s), M/L COPvel (2.6 ± 0.5 cm/s vs. 2.9 ± 0.5 cm/s), M/L COPsd (0.63 ± 0.12 cm vs. 0.73 ± 0.11 cm), M/L COPmax (1.76 ± 0.25 cm vs. 1.98 ± 0.25 cm), and COParea (0.13 ± 0.03 cm2 vs. 0.16 ± 0.04 cm2) than the pooled means of the CCT and control groups (P < 0.05). Conclusion Reduced values in COP measures indicated postural stability improvements. Thus, six weeks of coordination training with SR stimulation enhanced postural stability. Future research should examine the use of SR stimulation for decreasing recurrent ankle sprain injury in physically active individuals with FAI. PMID:18086314

Adverse systemic arterial function in patients with selenium deficiency.

PubMed

Chan, Y-H; Siu, C-W; Yiu, K-H; Chan, H-T; Li, S-W; Tam, S; Cheung, B M; Lau, C-P; Lam, T H; Tse, H-F

2012-01-01

Experimental studies have shown that selenium is involved in the synthesis of selenoproteins which might contribute to cardiovascular protection. However, the relationship between selenium deficiency and vascular function in clinical context remains unknown. To investigate for any relationship between selenium deficiency and systemic arterial function in patients with high risk of vascular events. Cross-sectional study. 306 consecutive patients with high risk for cardiovascular events (coronary artery disease 35%, acute/ recurrent ischemic stroke 40%, diabetes mellitus 54%) followed up at internal medicine outpatient clinics. Non-invasive brachial-ankle pulse wave velocity (PWV) was determined using vascular profiling system (VP-2000). Long-term intake of selenium was determined by a validated food frequency questionnaire. Mean daily selenium intake was 59.5 ± 52.1 mcg/day, and mean PWV was 1782.4 ± 418.4 cm/s. Patients with selenium intake <10th percentile had significantly higher PWV as compared to patients with intake ≥ 10th percentile (1968.2 ± 648.9 cm/s versus 1762.2 ± 381.6 cm/s, P=0.010). After adjusting for potential confounders including age, gender, history of hypertension, hyperlipidemia, diabetes and cardiovascular disease, smoking status, use of cardiovascular medications, waist-hip ratio, education/ financial status, physical activity, calorie intake and intake of antioxidant vitamins, deficient selenium intake <10th percentile remained independently predictive of increased PWV by +363.4 cm/s [95% CI: 68.1 to 658.6, P=0.016, relative increase 21%]. Selenium deficiency is associated with adverse arterial function in patients with high risk for vascular events.

Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus

PubMed Central

Jiang, Bo; Xiong, Zhe; Yang, Jun; Wang, Wei; Wang, Yue; Hu, Zhuang-Li; Wang, Fang; Chen, Jian-Guo

2012-01-01

BACKGROUND AND PURPOSE Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients of Panax ginseng with little toxicity and has been shown to have neuroprotective effects. In this study, we investigated the antidepressant-like effect of Rg1 in models of depression in mice. EXPERIMENTAL APPROACH The effects of Rg1 were assessed in the forced swimming test (FST) and tail suspension test (TST) in mice. Rg1 was also investigated in the chronic mild stress (CMS) mouse model of depression with imipramine as the positive control. Changes in hippocampal neurogenesis and spine density, the brain-derived neurotrophic factor (BDNF) signalling pathway, and serum corticosterone level after chronic stress and Rg1 treatment were then investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressive mechanisms of Rg1. KEY RESULTS Ginsenoside Rg1 exhibited antidepressant-like activity in the FST and TST in mice without affecting locomotor activity. It was also effective in the CMS model of depression. Furthermore, Rg1 up-regulated the BDNF signalling pathway in the hippocampus and down-regulated serum corticosterone level during the CMS procedure. In addition, Rg1 was able to reverse the decrease in dendritic spine density and hippocampal neurogenesis caused by CMS. However, Rg1 had no discernable effect on the monoaminergic system. CONCLUSIONS AND IMPLICATIONS Our results provide the first evidence that Rg1 has antidepressant activity via activation of the BDNF signalling pathway and up-regulation of hippocampal neurogenesis. PMID:22335772

42 CFR 423.2063 - Applicability of laws, regulations and CMS Rulings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Applicability of laws, regulations and CMS Rulings..., ALJ Hearings, MAC review, and Judicial Review § 423.2063 Applicability of laws, regulations and CMS... on ALJs and the MAC. (b) CMS Rulings are published under the authority of the CMS Administrator...

42 CFR 426.517 - CMS' statement regarding new evidence.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false CMS' statement regarding new evidence. 426.517... DETERMINATIONS Review of an NCD § 426.517 CMS' statement regarding new evidence. (a) CMS may review any new... experts; and (5) Presented during any hearing. (b) CMS may submit a statement regarding whether the new...

42 CFR 405.1063 - Applicability of laws, regulations and CMS Rulings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Applicability of laws, regulations and CMS Rulings... Medicare Coverage Policies § 405.1063 Applicability of laws, regulations and CMS Rulings. (a) All laws and... the MAC. (b) CMS Rulings are published under the authority of the Administrator, CMS. Consistent with...

How to Spot Congenital Myasthenic Syndromes Resembling the Lambert-Eaton Myasthenic Syndrome? A Brief Review of Clinical, Electrophysiological, and Genetics Features.

PubMed

Lorenzoni, Paulo José; Scola, Rosana Herminia; Kay, Claudia Suemi Kamoi; Werneck, Lineu Cesar; Horvath, Rita; Lochmüller, Hanns

2018-06-01

Congenital myasthenic syndromes (CMS) are heterogeneous genetic diseases in which neuromuscular transmission is compromised. CMS resembling the Lambert-Eaton myasthenic syndrome (CMS-LEMS) are emerging as a rare group of distinct presynaptic CMS that share the same electrophysiological features. They have low compound muscular action potential amplitude that increment after brief exercise (facilitation) or high-frequency repetitive nerve stimulation. Although clinical signs similar to LEMS can be present, the main hallmark is the electrophysiological findings, which are identical to autoimmune LEMS. CMS-LEMS occurs due to deficits in acetylcholine vesicle release caused by dysfunction of different components in its pathway. To date, the genes that have been associated with CMS-LEMS are AGRN, SYT2, MUNC13-1, VAMP1, and LAMA5. Clinicians should keep in mind these newest subtypes of CMS-LEMS to achieve the correct diagnosis and therapy. We believe that CMS-LEMS must be included as an important diagnostic clue to genetic investigation in the diagnostic algorithms to CMS. We briefly review the main features of CMS-LEMS.

42 CFR 482.70 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... geographic area specified by CMS. Heart-Lung transplant center means a transplant center that is located in a hospital with an existing Medicare-approved heart transplant center and an existing Medicare-approved lung center that performs combined heart-lung transplants. Intestine transplant center means a Medicare...

42 CFR 482.70 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... geographic area specified by CMS. Heart-Lung transplant center means a transplant center that is located in a hospital with an existing Medicare-approved heart transplant center and an existing Medicare-approved lung center that performs combined heart-lung transplants. Intestine transplant center means a Medicare...

42 CFR 482.70 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... geographic area specified by CMS. Heart-Lung transplant center means a transplant center that is located in a hospital with an existing Medicare-approved heart transplant center and an existing Medicare-approved lung center that performs combined heart-lung transplants. Intestine transplant center means a Medicare...

42 CFR 482.70 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... geographic area specified by CMS. Heart-Lung transplant center means a transplant center that is located in a hospital with an existing Medicare-approved heart transplant center and an existing Medicare-approved lung center that performs combined heart-lung transplants. Intestine transplant center means a Medicare...

78 FR 23690 - Airworthiness Directives; The Boeing Company

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-22

... management system (CMS) configuration database; and installing new operational program software (OPS) for the CSCP, zone management unit (ZMU), passenger address controller, cabin interphone controller, cabin area... on the Internet at http://www.regulations.gov ; or in person at the Docket Management Facility...

A novel photo-grafting of acrylamide onto carboxymethyl starch. 1. Utilization of CMS-g-PAAm in easy care finishing of cotton fabrics.

PubMed

El-Sheikh, Manal A

2016-11-05

The photosensitized grafting of vinyl monomers onto a range of polymeric substrates has been the subject of particular interest in the recent past. Carboxymethyl starch (CMS)-poly acrylamide (PAAm) graft copolymer (CMS-g-PAAm) with high graft yield was successfully prepared by grafting of acrylamide onto CMS using UV irradiation in the presence of the water soluble 4-(trimethyl ammoniummethyl) benzophenone chloride photoinitiator. CMS-g-PAAm with nitrogen content of 8.3% and grafting efficiency up to 98.9% was obtained using 100% AAm, a material: liquor ratio of 1:14 and 1% photinitiator at 30°C for 1h of UV irradiation. The synthesis of CMS-g-PAAm was confirmed by FTIR and Nitrogen content (%). Surface morphology of CMS and surface morphological changes of CMS after grafting with AAm were studied using SEM. Thermal properties of both CMS and CMS-g-PAAm were studied using TGA and DSC. To impart easy care finishing to cotton fabrics, aqueous formulations of: CMS-g-PAAm, dimethylol dihydroxy ethylene urea (DMDHEU), CMS-g-PAAm-DMDHEU mixture or methylolated CMS-g-PAAm were used. Cotton fabrics were padded in these formulations, squeezed to a wet pick up 100%, dried at 100°C for 5min, cured at 150°C for 5min, washed at 50°C for 10min and air-dried. CRA (crease recovery angle) of untreated fabrics and fabrics finished with a mixture of 2% CMS-g-PAAm and 10% DMDHEU or methylolated CMS-g-PAAm (10% formaldehyde) were: 136°, 190°, 288° respectively. Increasing the number of washing cycles up to five cycles results in an insignificant decrease in the CRA and a significant decrease in RF (releasable formaldehyde) of finished fabric samples. The morphologies of the finished and unfinished cotton fabrics were performed by SEM. Copyright © 2016 Elsevier Ltd. All rights reserved.

Perceptions, use and attitudes of pharmacy customers on complementary medicines and pharmacy practice

PubMed Central

2010-01-01

Background Complementary medicines (CMs) are popular amongst Australians and community pharmacy is a major supplier of these products. This study explores pharmacy customer use, attitudes and perceptions of complementary medicines, and their expectations of pharmacists as they relate to these products. Methods Pharmacy customers randomly selected from sixty large and small, metropolitan and rural pharmacies in three Australian states completed an anonymous, self administered questionnaire that had been pre-tested and validated. Results 1,121 customers participated (response rate 62%). 72% had used CMs within the previous 12 months, 61% used prescription medicines daily and 43% had used both concomitantly. Multivitamins, fish oils, vitamin C, glucosamine and probiotics were the five most popular CMs. 72% of people using CMs rated their products as 'very effective' or 'effective enough'. CMs were as frequently used by customers aged 60 years or older as younger customers (69% vs. 72%) although the pattern of use shifted with older age. Most customers (92%) thought pharmacists should provide safety information about CMs, 90% thought they should routinely check for interactions, 87% thought they should recommend effective CMs, 78% thought CMs should be recorded in customer's medication profile and 58% thought pharmacies stocking CMs should also employ a complementary medicine practitioner. Of those using CMs, 93% thought it important for pharmacists to be knowledgeable about CMs and 48% felt their pharmacist provides useful information about CMs. Conclusions CMs are widely used by pharmacy customers of all ages who want pharmacists to be more involved in providing advice about these products. PMID:20646290

Recombination Events Involving the atp9 Gene Are Associated with Male Sterility of CMS PET2 in Sunflower

PubMed Central

Reddemann, Antje; Horn, Renate

2018-01-01

Cytoplasmic male sterility (CMS) systems represent ideal mutants to study the role of mitochondria in pollen development. In sunflower, CMS PET2 also has the potential to become an alternative CMS source for commercial sunflower hybrid breeding. CMS PET2 originates from an interspecific cross of H. petiolaris and H. annuus as CMS PET1, but results in a different CMS mechanism. Southern analyses revealed differences for atp6, atp9 and cob between CMS PET2, CMS PET1 and the male-fertile line HA89. A second identical copy of atp6 was present on an additional CMS PET2-specific fragment. In addition, the atp9 gene was duplicated. However, this duplication was followed by an insertion of 271 bp of unknown origin in the 5′ coding region of the atp9 gene in CMS PET2, which led to the creation of two unique open reading frames orf288 and orf231. The first 53 bp of orf288 are identical to the 5′ end of atp9. Orf231 consists apart from the first 3 bp, being part of the 271-bp-insertion, of the last 228 bp of atp9. These CMS PET2-specific orfs are co-transcribed. All 11 editing sites of the atp9 gene present in orf231 are fully edited. The anther-specific reduction of the co-transcript in fertility-restored hybrids supports the involvement in male-sterility based on CMS PET2. PMID:29534485

Hybrid male sterility in Mimulus (Phrymaceae) is associated with a geographically restricted mitochondrial rearrangement.

PubMed

Case, Andrea L; Willis, John H

2008-05-01

Cytoplasmic male sterility (CMS) and nuclear fertility restoration (Rf) involves intergenomic coevolution. Although male-sterile phenotypes are rarely expressed in natural populations of angiosperms, CMS genes are thought to be common. The evolutionary dynamics of CMS/Rf systems are poorly understood, leaving gaps in our understanding of mechanisms and consequences of cytonuclear interactions. We characterized the molecular basis and geographic distribution of a CMS gene in Mimulus guttatus. We used outcrossing M. guttatus (with CMS and Rf) to self-fertilizing M. nasutus (lacking CMS and Rf) to generate hybrids segregating for CMS. Mitochondrial transcripts containing an essential gene (nad6) were perfectly associated with male sterility. The CMS mitotype was completely absent in M. nasutus, present in all genotypes collected from the original collection site, but in only two individuals from 34 other M. guttatus populations. This pattern suggests that the CMS likely originated at a single locality, spread to fixation within the population, but has not spread to other populations, indicating possible ecological or genetic constraints on dispersal of this CMS mitotype between populations. Extreme localization may be characteristic of CMS in hermaphroditic species, in contrast to geographically widespread mitotypes commonly found in gynodioecious species, and could directly contribute to hybrid incompatibilities in nature.

Controls on the global distribution of contourite drifts: Insights from an eddy-resolving ocean model

NASA Astrophysics Data System (ADS)

Thran, Amanda C.; Dutkiewicz, Adriana; Spence, Paul; Müller, R. Dietmar

2018-05-01

Contourite drifts are anomalously high sediment accumulations that form due to reworking by bottom currents. Due to the lack of a comprehensive contourite database, the link between vigorous bottom water activity and drift occurrence has yet to be demonstrated on a global scale. Using an eddy-resolving ocean model and a new georeferenced database of 267 contourites, we show that the global distribution of modern contourite drifts strongly depends on the configuration of the world's most powerful bottom currents, many of which are associated with global meridional overturning circulation. Bathymetric obstacles frequently modify flow direction and intensity, imposing additional finer-scale control on drift occurrence. Mean bottom current speed over contourite-covered areas is only slightly higher (2.2 cm/s) than the rest of the global ocean (1.1 cm/s), falling below proposed thresholds deemed necessary to re-suspend and redistribute sediments (10-15 cm/s). However, currents fluctuate more frequently and intensely over areas with drifts, highlighting the role of intermittent, high-energy bottom current events in sediment erosion, transport, and subsequent drift accumulation. We identify eddies as a major driver of these bottom current fluctuations, and we find that simulated bottom eddy kinetic energy is over three times higher in contourite-covered areas in comparison to the rest of the ocean. Our work supports previous hypotheses which suggest that contourite deposition predominantly occurs due to repeated acute events as opposed to continuous reworking under average-intensity background flow conditions. This suggests that the contourite record should be interpreted in terms of a bottom current's susceptibility to experiencing periodic, high-speed current events. Our results also highlight the potential role of upper ocean dynamics in contourite sedimentation through its direct influence on deep eddy circulation.

Angle-corrected imaging transcranial doppler sonography versus imaging and nonimaging transcranial doppler sonography in children with sickle cell disease.

PubMed

Krejza, J; Rudzinski, W; Pawlak, M A; Tomaszewski, M; Ichord, R; Kwiatkowski, J; Gor, D; Melhem, E R

2007-09-01

Nonimaging transcranial Doppler sonography (TCD) and imaging TCD (TCDI) are used for determination of the risk of stroke in children with sickle cell disease (SCD). The purpose was to compare angle-corrected, uncorrected TCDI, and TCD blood flow velocities in children with SCD. A total of 37 children (mean age, 7.8 +/- 3.0 years) without intracranial arterial narrowing determined with MR angiography, were studied with use of TCD and TCDI at the same session. Depth of insonation and TCDI mean velocities with and without correction for the angle of insonation in the terminal internal carotid artery (ICA) and middle (MCA), anterior (ACA), and posterior (PCA) cerebral arteries were compared with TCD velocities with use of a paired t test. Two arteries were not found on TCDI compared with 15 not found on TCD. Average angle of insonation in the MCA, ACA, ICA, and PCA was 31 degrees , 44 degrees , 25 degrees , and 29 degrees , respectively. TCDI and TCD mean depth of insonation for all arteries did not differ significantly; however, individual differences varied substantially. TCDI velocities were significantly lower than TCD velocities, respectively, for the right and left sides (mean +/- SD): MCA, 106 +/- 22 cm/s and 111 +/- 33 cm/s versus 130 +/- 19 cm/s and 134 +/- 26 cm/s; ICA, 90 +/- 14 cm/s and 98 +/- 27 cm/s versus 117 +/- 18 cm/s and 119 +/- 23 cm/s; ACA, 74 +/- 24 cm/s and 88 +/- 25 cm/s versus 105 +/- 23 cm/s and 105 +/- 31 cm/s; and PCA, 84 +/- 27 cm/s and 82 +/- 21 cm/s versus 95 +/- 23 cm/s and 94 +/- 20 cm/s. TCD and angle-corrected TCDI velocities were not statistically different except for higher angle-corrected TCDI values in the left ACA and right PCA. TCD velocities are significantly higher than TCDI velocities but are not different from the angle-corrected TCDI velocities. TCDI identifies the major intracranial arteries more effectively than TCD.

42 CFR 488.417 - Denial of payment for all new admissions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... to CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State (for non-State operated NFs against which CMS is imposing no remedies); and (2) CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State...

42 CFR 488.417 - Denial of payment for all new admissions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... to CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State (for non-State operated NFs against which CMS is imposing no remedies); and (2) CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State...

42 CFR 488.417 - Denial of payment for all new admissions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... to CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State (for non-State operated NFs against which CMS is imposing no remedies); and (2) CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State...

42 CFR 488.417 - Denial of payment for all new admissions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... to CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State (for non-State operated NFs against which CMS is imposing no remedies); and (2) CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State...

42 CFR 488.417 - Denial of payment for all new admissions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... to CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State (for non-State operated NFs against which CMS is imposing no remedies); and (2) CMS (for all facilities except non-State operated NFs against which CMS is imposing no remedies) or the State...

45 CFR 150.317 - Factors CMS uses to determine the amount of penalty.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Factors CMS uses to determine the amount of... RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement With Respect to Issuers and Non-Federal Governmental Plans-Civil Money Penalties § 150.317 Factors CMS...

40 CFR Table 1 to Subpart Qqqqq of... - Applicability of General Provisions to Subpart QQQQQ

Code of Federal Regulations, 2010 CFR

2010-07-01

.... § 63.8(e) CMS Performance Evaluation No Subpart QQQQQ does not require CMS performance evaluations... QQQQQ does not require performance tests or CMS performance evaluations. § 63.9(e) Notification of... CMS No Subpart QQQQQ does not require CMS performance evaluations. § 63.10(a), (b), (d)(1), (d)(4)-(5...

42 CFR 405.753 - Appeal of a categorization of a device.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false Appeal of a categorization of a device. 405.753... Under Medicare Part A § 405.753 Appeal of a categorization of a device. (a) CMS's acceptance of the FDA categorization of a device as an experimental/investigational (Category A) device under § 405.203 is a national...

42 CFR 405.877 - Appeal of a categorization of a device.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Appeal of a categorization of a device. 405.877... Part B Program § 405.877 Appeal of a categorization of a device. (a) CMS's acceptance of the FDA categorization of a device as an experimental/investigational (Category A) device under § 405.203 is a national...

42 CFR 405.877 - Appeal of a categorization of a device.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false Appeal of a categorization of a device. 405.877... Part B Program § 405.877 Appeal of a categorization of a device. (a) CMS's acceptance of the FDA categorization of a device as an experimental/investigational (Category A) device under § 405.203 is a national...

42 CFR 405.753 - Appeal of a categorization of a device.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Appeal of a categorization of a device. 405.753... Under Medicare Part A § 405.753 Appeal of a categorization of a device. (a) CMS's acceptance of the FDA categorization of a device as an experimental/investigational (Category A) device under § 405.203 is a national...

The High-Luminosity upgrade of the LHC: Physics and Technology Challenges for the Accelerator and the Experiments

NASA Astrophysics Data System (ADS)

Schmidt, Burkhard

2016-04-01

In the second phase of the LHC physics program, the accelerator will provide an additional integrated luminosity of about 2500/fb over 10 years of operation to the general purpose detectors ATLAS and CMS. This will substantially enlarge the mass reach in the search for new particles and will also greatly extend the potential to study the properties of the Higgs boson discovered at the LHC in 2012. In order to meet the experimental challenges of unprecedented pp luminosity, the experiments will need to address the aging of the present detectors and to improve the ability to isolate and precisely measure the products of the most interesting collisions. The lectures gave an overview of the physics motivation and described the conceptual designs and the expected performance of the upgrades of the four major experiments, ALICE, ATLAS, CMS and LHCb, along with the plans to develop the appropriate experimental techniques and a brief overview of the accelerator upgrade. Only some key points of the upgrade program of the four major experiments are discussed in this report; more information can be found in the references given at the end.

42 CFR 422.510 - Termination of contract by CMS.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (CONTINUED) MEDICARE PROGRAM MEDICARE ADVANTAGE PROGRAM Application Procedures and Contracts for Medicare Advantage Organizations § 422.510 Termination of contract by CMS. (a) Termination by CMS. CMS may at any...

The diverse use of clouds by CMS

DOE PAGES

Andronis, Anastasios; Bauer, Daniela; Chaze, Olivier; ...

2015-12-23

The resources CMS is using are increasingly being offered as clouds. In Run 2 of the LHC the majority of CMS CERN resources, both in Meyrin and at the Wigner Computing Centre, will be presented as cloud resources on which CMS will have to build its own infrastructure. This infrastructure will need to run all of the CMS workflows including: Tier 0, production and user analysis. In addition, the CMS High Level Trigger will provide a compute resource comparable in scale to the total offered by the CMS Tier 1 sites, when it is not running as part of themore » trigger system. During these periods a cloud infrastructure will be overlaid on this resource, making it accessible for general CMS use. Finally, CMS is starting to utilise cloud resources being offered by individual institutes and is gaining experience to facilitate the use of opportunistically available cloud resources. Lastly, we present a snap shot of this infrastructure and its operation at the time of the CHEP2015 conference.« less

The Status of the Cms Experiment

NASA Astrophysics Data System (ADS)

Green, Dan

The CMS experiment was completely assembled in the fall of 2008 after a decade of design, construction and installation. During the last two years, cosmic ray data were taken on a regular basis. These data have enabled CMS to align the detector components, both spatially and temporally. Initial use of muons has also established the relative alignment of the CMS tracking and muon systems. In addition, the CMS calorimetry has been crosschecked with test beam data, thus providing an initial energy calibration of CMS calorimetry to about 5%. The CMS magnet has been powered and field mapped. The trigger and data acquisition systems have been installed and run at full speed. The tiered data analysis system has been exercised at full design bandwidth for Tier0, Tier1 and Tier2 sites. Monte Carlo simulation of the CMS detector has been constructed at a detailed geometric level and has been tuned to test beam and other production data to provide a realistic model of the CMS detector prior to first collisions.

Cardiotoxicity evaluation using human embryonic stem cells and induced pluripotent stem cell-derived cardiomyocytes.

PubMed

Zhao, Qi; Wang, Xijie; Wang, Shuyan; Song, Zheng; Wang, Jiaxian; Ma, Jing

2017-03-09

Cardiotoxicity remains an important concern in drug discovery. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have become an attractive platform to evaluate cardiotoxicity. However, the consistency between human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in prediction of cardiotoxicity has yet to be elucidated. Here we screened the toxicities of four representative drugs (E-4031, isoprenaline, quinidine, and haloperidol) using both hESC-CMs and hiPSC-CMs, combined with an impedance-based bioanalytical method. It showed that both hESC-CMs and hiPSC-CMs can recapitulate cardiotoxicity and identify the effects of well-characterized compounds. The combined platform of hPSC-CMs and an impedance-based bioanalytical method could improve preclinical cardiotoxicity screening, holding great potential for increasing drug development accuracy.

Resident intruder paradigm-induced aggression relieves depressive-like behaviors in male rats subjected to chronic mild stress

PubMed Central

Wei, Sheng; Ji, Xiao-wei; Wu, Chun-ling; Li, Zi-fa; Sun, Peng; Wang, Jie-qiong; Zhao, Qi-tao; Gao, Jie; Guo, Ying-hui; Sun, Shi-guang; Qiao, Ming-qi

2014-01-01

Background Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that the resident intruder paradigm (RIP) results in aggressive behavior in male rats. However, it is not known how resident intruder paradigm-induced aggression affects depressive-like behavior in isolated male rats subjected to chronic mild stress (CMS), which is an animal model of depression. Material/Methods Male Wistar rats were divided into 3 groups: non-stressed controls, isolated rats subjected to the CMS protocol, and resident intruder paradigm-exposed rats subjected to the CMS protocol. Results In the sucrose intake test, ingestion of a 1% sucrose solution by rats in the CMS group was significantly lower than in control and CMS+RIP rats after 3 weeks of stress. In the open-field test, CMS rats had significantly lower open-field scores compared to control rats. Furthermore, the total scores given the CMS group were significantly lower than in the CMS+RIP rats. In the forced swimming test (FST), the immobility times of CMS rats were significantly longer than those of the control or CMS+RIP rats. However, no differences were observed between controls and CMS+RIP rats. Conclusions Our data show that aggressive behavior evoked by the resident intruder paradigm could relieve broad-spectrum depressive-like behaviors in isolated adult male rats subjected to CMS. PMID:24911067

42 CFR 426.415 - CMS' role in the LCD review.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false CMS' role in the LCD review. 426.415 Section 426... Review of an LCD § 426.415 CMS' role in the LCD review. CMS may provide to the ALJ, and all parties to the LCD review, information identifying the person who represents the contractor or CMS, if necessary...

CMS-Wave

DTIC Science & Technology

2015-10-30

Coastal Inlets Research Program CMS -Wave CMS -Wave is a two-dimensional spectral wind-wave generation and transformation model that employs a forward...marching, finite-difference method to solve the wave action conservation equation. Capabilities of CMS -Wave include wave shoaling, refraction... CMS -Wave can be used in either on a half- or full-plane mode, with primary waves propagating from the seaward boundary toward shore. It can

A net-shaped multicellular formation facilitates the maturation of hPSC-derived cardiomyocytes through mechanical and electrophysiological stimuli

PubMed Central

Liu, Taoyan; Huang, Chengwu; Li, Hongxia; Wu, Fujian; Luo, Jianwen; Lu, Wenjing

2018-01-01

The use of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is limited in drug discovery and cardiac disease mechanism studies due to cell immaturity. Although many approaches have been reported to improve the maturation of hiPSC-CMs, the elucidation of the process of maturation is crucial. We applied a small-molecule-based differentiation method to generate cardiomyocytes (CMs) with multiple aggregation forms. The motion analysis revealed significant physical differences in the differently shaped CMs, and the net-shaped CMs had larger motion amplitudes and faster velocities than the sheet-shaped CMs. The net-shaped CMs displayed accelerated maturation at the transcriptional level and were more similar to CMs with a prolonged culture time (30 days) than to sheet-d15. Ion channel genes and gap junction proteins were up-regulated in net-shaped CMs, indicating that robust contraction was coupled with enhanced ion channel and connexin expression. The net-shaped CMs also displayed improved myofibril ultrastructure under transmission electron microscopy. In conclusion, different multicellular hPSC-CM structures, such as the net-shaped pattern, are formed using the conditioned induction method, providing a useful tool to improve cardiac maturation. PMID:29661985

76 FR 21908 - Statement of Organization, Functions, and Delegations of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-19

... areas of traditional and new media, including Web initiatives such as social media supported by innovative, increasingly mobile technologies; media relations; public information campaigns; and speechwriting. Serves as CMS' focal point in all activities related to the media. Provides consultation, advice...

Quality control for the first large areas of triple-GEM chambers for the CMS endcaps

NASA Astrophysics Data System (ADS)

Abbaneo, D.; Abbas, M.; Abbrescia, M.; Abi Akl, M.; Aboamer, O.; Acosta, D.; Ahmad, A.; Ahmed, W.; Aleksandrov, A.; Altieri, P.; Asawatangtrakuldee, C.; Aspell, P.; Assran, Y.; Awan, I.; Bally, S.; Ban, Y.; Banerjee, S.; Barashko, V.; Barria, P.; Bencze, G.; Beni, N.; Benussi, L.; Bhopatkar, V.; Bianco, S.; Bos, J.; Bouhali, O.; Braghieri, A.; Braibant, S.; Buontempo, S.; Calabria, C.; Caponero, M.; Caputo, C.; Cassese, F.; Castaneda, A.; Cauwenbergh, S.; Cavallo, F. R.; Celik, A.; Choi, M.; Choi, S.; Christiansen, J.; Cimmino, A.; Colafranceschi, S.; Colaleo, A.; Conde Garcia, A.; Czellar, S.; Dabrowski, M. M.; De Lentdecker, G.; De Oliveira, R.; de Robertis, G.; Dildick, S.; Dorney, B.; Endroczi, G.; Errico, F.; Fenyvesi, A.; Ferry, S.; Furic, I.; Giacomelli, P.; Gilmore, J.; Golovtsov, V.; Guiducci, L.; Guilloux, F.; Gutierrez, A.; Hadjiiska, R. M.; Hauser, J.; Hoepfner, K.; Hohlmann, M.; Hoorani, H.; Iaydjiev, P.; Jeng, Y. G.; Kamon, T.; Karchin, P.; Korytov, A.; Krutelyov, S.; Kumar, A.; Kim, H.; Lee, J.; Lenzi, T.; Litov, L.; Loddo, F.; Madorsky, A.; Maerschalk, T.; Maggi, M.; Magnani, A.; Mal, P. K.; Mandal, K.; Marchioro, A.; Marinov, A.; Majumdar, N.; Merlin, J. A.; Mitselmakher, G.; Mohanty, A. K.; Mohapatra, A.; Molnar, J.; Muhammad, S.; Mukhopadhyay, S.; Naimuddin, M.; Nuzzo, S.; Oliveri, E.; Pant, L. M.; Paolucci, P.; Park, I.; Passeggio, G.; Pavlov, B.; Philipps, B.; Piccolo, D.; Postema, H.; Puig Baranac, A.; Radi, A.; Radogna, R.; Raffone, G.; Ranieri, A.; Rashevski, G.; Riccardi, C.; Rodozov, M.; Rodrigues, A.; Ropelewski, L.; RoyChowdhury, S.; Ryu, G.; Ryu, M. S.; Safonov, A.; Salva, S.; Saviano, G.; Sharma, A.; Sharma, A.; Sharma, R.; Shah, A. H.; Shopova, M.; Sturdy, J.; Sultanov, G.; Swain, S. K.; Szillasi, Z.; Talvitie, J.; Tatarinov, A.; Tuuva, T.; Tytgat, M.; Vai, I.; Van Stenis, M.; Venditti, R.; Verhagen, E.; Verwilligen, P.; Vitulo, P.; Volkov, S.; Vorobyev, A.; Wang, D.; Wang, M.; Yang, U.; Yang, Y.; Yonamine, R.; Zaganidis, N.; Zenoni, F.; Zhang, A.

2018-02-01

The CMS Collaboration plans to equip the very forward muon system with triple-GEM detectors that can withstand the environment of the High-Luminosity LHC. This project is at the final stages of R&D and moving to production. An unprecedented large area of several 100 m2 are to be instrumented with GEM detectors which will be produced in six different sites around the world. A common construction and quality control procedure is required to ensure the performance of each detector. The quality control steps will include optical inspection, cleaning and baking of all materials and parts used to build the detector, leakage current tests of the GEM foils, high voltage tests, gas leak tests of the chambers and monitoring pressure drop vs. time, gain calibration to know the optimal operation region of the detector, gain uniformity tests, and studying the efficiency, noise and tracking performance of the detectors in a cosmic stand using scintillators.

3D crustal structure and long-period ground motions from a M9.0 megathrust earthquake in the Pacific Northwest region

USGS Publications Warehouse

Olsen, K.B.; Stephenson, W.J.; Geisselmeyer, A.

2008-01-01

We have developed a community velocity model for the Pacific Northwest region from northern California to southern Canada and carried out the first 3D simulation of a Mw 9.0 megathrust earthquake rupturing along the Cascadia subduction zone using a parallel supercomputer. A long-period (<0.5 Hz) source model was designed by mapping the inversion results for the December 26, 2004 Sumatra–Andaman earthquake (Han et al., Science 313(5787):658–662, 2006) onto the Cascadia subduction zone. Representative peak ground velocities for the metropolitan centers of the region include 42 cm/s in the Seattle area and 8–20 cm/s in the Tacoma, Olympia, Vancouver, and Portland areas. Combined with an extended duration of the shaking up to 5 min, these long-period ground motions may inflict significant damage on the built environment, in particular on the highrises in downtown Seattle.

Human renal adipose tissue induces the invasion and progression of renal cell carcinoma.

PubMed

Campo-Verde-Arbocco, Fiorella; López-Laur, José D; Romeo, Leonardo R; Giorlando, Noelia; Bruna, Flavia A; Contador, David E; López-Fontana, Gastón; Santiano, Flavia E; Sasso, Corina V; Zyla, Leila E; López-Fontana, Constanza M; Calvo, Juan C; Carón, Rubén W; Creydt, Virginia Pistone

2017-11-07

We evaluated the effects of conditioned media (CMs) of human adipose tissue from renal cell carcinoma located near the tumor (hRATnT) or farther away from the tumor (hRATfT), on proliferation, adhesion and migration of tumor (786-O and ACHN) and non-tumor (HK-2) human renal epithelial cell lines. Human adipose tissues were obtained from patients with renal cell carcinoma (RCC) and CMs from hRATnT and hRATfT incubation. Proliferation, adhesion and migration were quantified in 786-O, ACHN and HK-2 cell lines incubated with hRATnT-, hRATfT- or control-CMs. We evaluated versican, adiponectin and leptin expression in CMs from hRATnT and hRATfT. We evaluated AdipoR1/2, ObR, pERK, pAkt y pPI3K expression on cell lines incubated with CMs. No differences in proliferation of cell lines was found after 24 h of treatment with CMs. All cell lines showed a significant decrease in cell adhesion and increase in cell migration after incubation with hRATnT-CMs vs. hRATfT- or control-CMs. hRATnT-CMs showed increased levels of versican and leptin, compared to hRATfT-CMs. AdipoR2 in 786-O and ACHN cells decreased significantly after incubation with hRATfT- and hRATnT-CMs vs. control-CMs. We observed a decrease in the expression of pAkt in HK-2, 786-O and ACHN incubated with hRATnT-CMs. This result could partially explain the observed changes in migration and cell adhesion. We conclude that hRATnT released factors, such as leptin and versican, could enhance the invasive potential of renal epithelial cell lines and could modulate the progression of the disease.

Down-regulation of Inwardly Rectifying K+ Currents in Astrocytes Derived from Patients with Monge's Disease.

PubMed

Wu, Wei; Yao, Hang; Zhao, Helen W; Wang, Juan; Haddad, Gabriel G

2018-03-15

Chronic mountain sickness (CMS) or Monge's disease is a disease in highlanders. These patients have a variety of neurologic symptoms such as migraine, mental fatigue, confusion, dizziness, loss of appetite, memory loss and neuronal degeneration. The cellular and molecular mechanisms underlying CMS neuropathology is not understood. In the previous study, we demonstrated that neurons derived from CMS patients' fibroblasts have a decreased expression and altered gating properties of voltage-gated sodium channel. In this study, we further characterize the electrophysiological properties of iPSC-derived astrocytes from CMS patients. We found that the current densities of the inwardly rectifying potassium (Kir) channels in CMS astrocytes (-5.7 ± 2.2 pA/pF at -140 mV) were significantly decreased as compared to non-CMS (-28.4 ± 3.4 pA/pF at -140 mV) and sea level subjects (-28.3 ± 5.3 pA/pF at -140 mV). We further demonstrated that the reduced Kir current densities in CMS astrocytes were caused by their decreased protein expression of Kir4.1 and Kir2.3 channels, while single channel properties (i.e., P o , conductance) of Kir channel in CMS astrocytes were not altered. In addition, we found no significant differences of outward potassium currents between CMS and non-CMS astrocytes. As compared to non-CMS and sea level subjects, the K + uptake ability in CMS astrocytes was significantly decreased. Taken together, our results suggest that down-regulation of Kir channels and the resulting decreased K + uptake ability in astrocytes could be one of the major molecular mechanisms underlying the neurologic manifestations in CMS patients. Published by Elsevier Ltd.

From Early Embryonic to Adult Stage: Comparative Study of Action Potentials of Native and Pluripotent Stem Cell-Derived Cardiomyocytes.

PubMed

Peinkofer, Gabriel; Burkert, Karsten; Urban, Katja; Krausgrill, Benjamin; Hescheler, Jürgen; Saric, Tomo; Halbach, Marcel

2016-10-01

Cardiomyocytes (CMs) derived from induced pluripotent stem cells (iPS-CMs) are promising candidates for cell therapy, drug screening, and developmental studies. It is known that iPS-CMs possess immature electrophysiological properties, but an exact characterization of their developmental stage and subtype differentiation is hampered by a lack of knowledge of electrophysiological properties of native CMs from different developmental stages and origins within the heart. Thus, we sought to systematically investigate action potential (AP) properties of native murine CMs and to establish a database that allows classification of stem cell-derived CMs. Hearts from 129S2PasCrl mice were harvested at days 9-10, 12-14, and 16-18 postcoitum, as well as 1 day, 3-4 days, 1-2 weeks, 3-4 weeks, and 6 weeks postpartum. AP recordings in left and right atria and at apical, medial, and basal left and right ventricles were performed with sharp glass microelectrodes. Measurements revealed significant changes in AP morphology during pre- and postnatal murine development and significant differences between atria and ventricles, enabling a classification of developmental stage and subtype differentiation of stem cell-derived CMs based on their AP properties. For iPS-CMs derived from cell line TiB7.4, a typical ventricular phenotype was demonstrated at later developmental stages, while there were electrophysiological differences from atrial as well as ventricular native CMs at earlier stages. This finding supports that iPS-CMs can develop AP properties similar to native CMs, but points to differences in the maturation process between iPS-CMs and native CMs, which may be explained by dissimilar conditions during in vitro differentiation and in vivo development.

Pharmacokinetics of colistin methanesulfonate (CMS) in healthy Chinese subjects after single and multiple intravenous doses.

PubMed

Zhao, Miao; Wu, Xiao-Jie; Fan, Ya-Xin; Zhang, Ying-Yuan; Guo, Bei-Ning; Yu, Ji-Cheng; Cao, Guo-Ying; Chen, Yuan-Cheng; Wu, Ju-Fang; Shi, Yao-Guo; Li, Jian; Zhang, Jing

2018-05-01

The high prevalence of extensively drug-resistant Gram-negative pathogens has forced clinicians to use colistin as a last-line therapy. Knowledge on the pharmacokinetics of colistin methanesulfonate (CMS), an inactive prodrug, and colistin has increased substantially; however, the pharmacokinetics in the Chinese population is still unknown due to lack of a CMS product in China. This study aimed to evaluate the pharmacokinetics of a new CMS product developed in China in order to optimise dosing regimens. A total of 24 healthy subjects (12 female, 12 male) were enrolled in single- and multiple-dose pharmacokinetic (PK) studies. Concentrations of CMS and formed colistin in plasma and urine were measured, and PK analysis was conducted using a non-compartmental approach. Following a single CMS dose [2.36 mg colistin base activity (CBA) per kg, 1 h infusion], peak concentrations (C max ) of CMS and formed colistin were 18.0 mg/L and 0.661 mg/L, respectively. The estimated half-life (t 1/2 ) of CMS and colistin were 1.38 h and 4.49 h, respectively. Approximately 62.5% of the CMS dose was excreted via urine within 24 h after dosing, whilst only 1.28% was present in the form of colistin. Following multiple CMS doses, colistin reached steady-state within 24 h; there was no accumulation of CMS, but colistin accumulated slightly (R AUC  = 1.33). This study provides the first PK data in the Chinese population and is essential for designing CMS dosing regimens for use in Chinese hospitals. The urinary PK data strongly support the use of intravenous CMS for serious urinary tract infections. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Differences in pharmacokinetics and pharmacodynamics of colistimethate sodium (CMS) and colistin between three different CMS dosage regimens in a critically ill patient infected by a multidrug-resistant Acinetobacter baumannii.

PubMed

Luque, Sònia; Grau, Santiago; Valle, Marta; Sorlí, Luisa; Horcajada, Juan Pablo; Segura, Concha; Alvarez-Lerma, Francisco

2013-08-01

Use of colistin has re-emerged for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria, but information on its pharmacokinetics and pharmacodynamics is limited, especially in critically ill patients. Recent data from pharmacokinetic/pharmacodynamic (PK/PD) population studies have suggested that this population could benefit from administration of higher than standard doses of colistimethate sodium (CMS), but the relationship between administration of incremental doses of CMS and corresponding PK/PD parameters as well as its efficacy and toxicity have not yet been investigated in a clinical setting. The objective was to study the PK/PD differences of CMS and colistin between three different CMS dosage regimens in the same critically ill patient. A critically ill patient with nosocomial pneumonia caused by a MDR Acinetobacter baumannii received incremental doses of CMS. During administration of the different CMS dosage regimens, CMS and colistin plasma concentrations were determined and PK/PD indexes were calculated. With administration of the highest CMS dose once daily (720 mg every 24h), the peak plasma concentration of CMS and colistin increased to 40.51 mg/L and 1.81 mg/L, respectively, and the AUC0-24/MIC of colistin was 184.41. This dosage regimen was efficacious, and no nephrotoxicity or neurotoxicity was observed. In conclusion, a higher and extended-interval CMS dosage made it possible to increase the exposure of CMS and colistin in a critically ill patient infected by a MDR A. baumannii and allowed a clinical and microbiological optimal response to be achieved without evidence of toxicity. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Structural and Functional Maturation of Cardiomyocytes Derived from Human Pluripotent Stem Cells

PubMed Central

Lundy, Scott D.; Zhu, Wei-Zhong

2013-01-01

Despite preclinical studies demonstrating the functional benefit of transplanting human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) into damaged myocardium, the ability of these immature cells to adopt a more adult-like cardiomyocyte (CM) phenotype remains uncertain. To address this issue, we tested the hypothesis that prolonged in vitro culture of human embryonic stem cell (hESC)- and human induced pluripotent stem cell (hiPSC)-derived CMs would result in the maturation of their structural and contractile properties to a more adult-like phenotype. Compared to their early-stage counterparts (PSC-CMs after 20–40 days of in vitro differentiation and culture), late-stage hESC-CMs and hiPSC-CMs (80–120 days) showed dramatic differences in morphology, including increased cell size and anisotropy, greater myofibril density and alignment, sarcomeres visible by bright-field microscopy, and a 10-fold increase in the fraction of multinucleated CMs. Ultrastructural analysis confirmed improvements in the myofibrillar density, alignment, and morphology. We measured the contractile performance of late-stage hESC-CMs and hiPSC-CMs and noted a doubling in shortening magnitude with slowed contraction kinetics compared to the early-stage cells. We then examined changes in the calcium-handling properties of these matured CMs and found an increase in calcium release and reuptake rates with no change in the maximum amplitude. Finally, we performed electrophysiological assessments in hESC-CMs and found that late-stage myocytes have hyperpolarized maximum diastolic potentials, increased action potential amplitudes, and faster upstroke velocities. To correlate these functional changes with gene expression, we performed qPCR and found a robust induction of the key cardiac structural markers, including β-myosin heavy chain and connexin-43, in late-stage hESC-CMs and hiPSC-CMs. These findings suggest that PSC-CMs are capable of slowly maturing to more closely resemble the phenotype of adult CMs and may eventually possess the potential to regenerate the lost myocardium with robust de novo force-producing tissue. PMID:23461462

CMS Connect

NASA Astrophysics Data System (ADS)

Balcas, J.; Bockelman, B.; Gardner, R., Jr.; Hurtado Anampa, K.; Jayatilaka, B.; Aftab Khan, F.; Lannon, K.; Larson, K.; Letts, J.; Marra Da Silva, J.; Mascheroni, M.; Mason, D.; Perez-Calero Yzquierdo, A.; Tiradani, A.

2017-10-01

The CMS experiment collects and analyzes large amounts of data coming from high energy particle collisions produced by the Large Hadron Collider (LHC) at CERN. This involves a huge amount of real and simulated data processing that needs to be handled in batch-oriented platforms. The CMS Global Pool of computing resources provide +100K dedicated CPU cores and another 50K to 100K CPU cores from opportunistic resources for these kind of tasks and even though production and event processing analysis workflows are already managed by existing tools, there is still a lack of support to submit final stage condor-like analysis jobs familiar to Tier-3 or local Computing Facilities users into these distributed resources in an integrated (with other CMS services) and friendly way. CMS Connect is a set of computing tools and services designed to augment existing services in the CMS Physics community focusing on these kind of condor analysis jobs. It is based on the CI-Connect platform developed by the Open Science Grid and uses the CMS GlideInWMS infrastructure to transparently plug CMS global grid resources into a virtual pool accessed via a single submission machine. This paper describes the specific developments and deployment of CMS Connect beyond the CI-Connect platform in order to integrate the service with CMS specific needs, including specific Site submission, accounting of jobs and automated reporting to standard CMS monitoring resources in an effortless way to their users.

Ogura-CMS in Chinese cabbage (Brassica rapa ssp. pekinensis) causes delayed expression of many nuclear genes.

PubMed

Dong, Xiangshu; Kim, Wan Kyu; Lim, Yong-Pyo; Kim, Yeon-Ki; Hur, Yoonkang

2013-02-01

We investigated the mechanism regulating cytoplasmic male sterility (CMS) in Brassica rapa ssp. pekinensis using floral bud transcriptome analyses of Ogura-CMS Chinese cabbage and its maintainer line in B. rapa 300-K oligomeric probe (Br300K) microarrays. Ogura-CMS Chinese cabbage produced few and infertile pollen grains on indehiscent anthers. Compared to the maintainer line, CMS plants had shorter filaments and plant growth, and delayed flowering and pollen development. In microarray analysis, 4646 genes showed different expression, depending on floral bud size, between Ogura-CMS and its maintainer line. We found 108 and 62 genes specifically expressed in Ogura-CMS and its maintainer line, respectively. Ogura-CMS line-specific genes included stress-related, redox-related, and B. rapa novel genes. In the maintainer line, genes related to pollen coat and germination were specifically expressed in floral buds longer than 3mm, suggesting insufficient expression of these genes in Ogura-CMS is directly related to dysfunctional pollen. In addition, many nuclear genes associated with auxin response, ATP synthesis, pollen development and stress response had delayed expression in Ogura-CMS plants compared to the maintainer line, which is consistent with the delay in growth and development of Ogura-CMS plants. Delayed expression may reduce pollen grain production and/or cause sterility, implying that mitochondrial, retrograde signaling delays nuclear gene expression. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Phospholipase A2 activity-dependent and -independent fusogenic activity of Naja nigricollis CMS-9 on zwitterionic and anionic phospholipid vesicles.

PubMed

Chiou, Yi-Ling; Chen, Ying-Jung; Lin, Shinne-Ren; Chang, Long-Sen

2011-11-01

CMS-9, a phospholipase A(2) (PLA(2)) from Naja nigricollis venom, induced the death of human breast cancer MCF-7 cells accompanied with the formation of cell clumps without clear boundaries between cells. Annexin V-FITC staining indicated that abundant phosphatidylserine appeared on the outer membrane of MCF-7 cell clumps, implying the possibility that CMS-9 may promote membrane fusion via anionic phospholipids. To validate this proposition, fusogenic activity of CMS-9 on vesicles composed of zwitterionic phospholipid alone or a combination of zwitterionic and anionic phospholipids was examined. Although CMS-9-induced fusion of zwitterionic phospholipid vesicles depended on PLA(2) activity, CMS-9-induced fusion of vesicles containing anionic phospholipids could occur without the involvement of PLA(2) activity. Membrane-damaging activity of CMS-9 was associated with its fusogenicity. Moreover, CMS-9 induced differently membrane leakage and membrane fusion of vesicles with different compositions. Membrane fluidity and binding capability with phospholipid vesicles were not related to the fusogenicity of CMS-9. However, membrane-bound conformation and mode of CMS-9 depended on phospholipid compositions. Collectively, our data suggest that PLA(2) activity-dependent and -independent fusogenicity of CMS-9 are closely related to its membrane-bound modes and targeted membrane compositions. Copyright © 2011 Elsevier Ltd. All rights reserved.

The impact of LHC jet data on the MMHT PDF fit at NNLO

NASA Astrophysics Data System (ADS)

Harland-Lang, L. A.; Martin, A. D.; Thorne, R. S.

2018-03-01

We investigate the impact of the high precision ATLAS and CMS 7 TeV measurements of inclusive jet production on the MMHT global PDF analysis at next-to-next-to-leading order (NNLO). This is made possible by the recent completion of the long-term project to calculate the NNLO corrections to the hard cross section. We find that a good description of the ATLAS data is not possible with the default treatment of experimental systematic errors, and propose a simplified solution that retains the dominant physical information of the data. We then investigate the fit quality and the impact on the gluon PDF central value and uncertainty when the ATLAS and CMS data are included in a MMHT fit. We consider both common choices for the factorization and renormalization scale, namely the inclusive jet transverse momentum, p_\\perp , and the leading jet p_\\perp , as well as the different jet radii for which the ATLAS and CMS data are made available. We find that the impact of these data on the gluon is relatively insensitive to these inputs, in particular the scale choice, while the inclusion of NNLO corrections tends to improve the data description somewhat and has a qualitatively similar though not identical impact on the gluon in comparison to NLO.

Construction and performance of a long-term earthen liner experiment

USGS Publications Warehouse

Cartwright, Keros; Krapac, Ivan G.; Bonaparte, Rudolph

1990-01-01

In land burial schemes, compacted soil barriers with low hydraulic conductivity are commonly used in cover and liner systems to control the movement of liquids and prevent groundwater contamination. An experimental liner measuring 8 x 15 x 0.9 m was constructed with design criteria and equipment to simulate construction of soil liners built at waste disposal facilities. The surface of the liner was flooded with a 29.5 cm deep pond on April 12, 1988. Infiltration of water into the liner has been monitored for two years using 4 large-ring (1.5 m OD) and 32 small-ring (0.28 m OD) infiltrometers, and a water-balance that accounts for total infiltration and evaporation. Average long-term infiltration fluxes based on two years of monitoring are 5.8 x 10-9 cm/s, 6.0 x 10-8 cm/s and 5.6 x 10-8 for the large-ring, small-ring, and water-balance data, respectively. The saturated hydraulic conductivity of the liner based on small-ring data, estimated using Darcy's Law and the Green-Ampt Approximation, is 3 x 10-8 and 4 x 10-8 cm/s, respectively. All sets of data indicate that the liner's performance exceed that which is required by the U.S. EPA.

Cerebral blood flow velocity in humans exposed to 24 h of head-down tilt

NASA Technical Reports Server (NTRS)

Kawai, Y.; Murthy, G.; Watenpaugh, D. E.; Breit, G. A.; Deroshia, C. W.; Hargens, A. R.

1993-01-01

This study investigates cerebral blood flow (CBF) velocity in humans before, during, and after 24 h of 6 deg head-down tilt (HDT), which is a currently accepted experimental model to simulate microgravity. CBF velocity was measured by use of the transcranial Doppler technique in the right middle cerebral artery of eight healthy male subjects. Mean CBF velocity increased from the pre-HDT upright seated baseline value of 55.5 +/- 3.7 (SE) cm/s to 61.5 +/- 3.3 cm/s at 0.5 h of HDT, reached a peak value of 63.2 +/- 4.1 cm/s at 3 h of HDT, and remained significantly above the pre-HDT baseline for over 6 h of HDT. During upright seated recovery, mean CBF velocity decreased to 87 percent of the pre-HDT baseline value. Mean CBF velocity correlated well with calculated intracranial arterial pressure (IAP). As analyzed by linear regression, mean CBF velocity = 29.6 + 0.32IAP. These results suggest that HDT increases CBF velocity by increasing IAP during several hours after the onset of microgravity. Importantly, the decrease in CBF velocity after HDT may be responsible, in part, for the increased risk of syncope observed in subjects after prolonged bed rest and also in astronauts returning to Earth.

42 CFR 411.382 - CMS's right to rescind advisory opinions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... rescind advisory opinions. Any advice CMS gives in an opinion does not prejudice its right to reconsider... faith reliance upon CMS's advice under this part, provided— (a) The requestor presented to CMS a full...

42 CFR 411.382 - CMS's right to rescind advisory opinions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... rescind advisory opinions. Any advice CMS gives in an opinion does not prejudice its right to reconsider... faith reliance upon CMS's advice under this part, provided— (a) The requestor presented to CMS a full...

Cluster size statistic and cluster mass statistic: two novel methods for identifying changes in functional connectivity between groups or conditions.

PubMed

Ing, Alex; Schwarzbauer, Christian

2014-01-01

Functional connectivity has become an increasingly important area of research in recent years. At a typical spatial resolution, approximately 300 million connections link each voxel in the brain with every other. This pattern of connectivity is known as the functional connectome. Connectivity is often compared between experimental groups and conditions. Standard methods used to control the type 1 error rate are likely to be insensitive when comparisons are carried out across the whole connectome, due to the huge number of statistical tests involved. To address this problem, two new cluster based methods--the cluster size statistic (CSS) and cluster mass statistic (CMS)--are introduced to control the family wise error rate across all connectivity values. These methods operate within a statistical framework similar to the cluster based methods used in conventional task based fMRI. Both methods are data driven, permutation based and require minimal statistical assumptions. Here, the performance of each procedure is evaluated in a receiver operator characteristic (ROC) analysis, utilising a simulated dataset. The relative sensitivity of each method is also tested on real data: BOLD (blood oxygen level dependent) fMRI scans were carried out on twelve subjects under normal conditions and during the hypercapnic state (induced through the inhalation of 6% CO2 in 21% O2 and 73%N2). Both CSS and CMS detected significant changes in connectivity between normal and hypercapnic states. A family wise error correction carried out at the individual connection level exhibited no significant changes in connectivity.

Cluster Size Statistic and Cluster Mass Statistic: Two Novel Methods for Identifying Changes in Functional Connectivity Between Groups or Conditions

PubMed Central

Ing, Alex; Schwarzbauer, Christian

2014-01-01

Functional connectivity has become an increasingly important area of research in recent years. At a typical spatial resolution, approximately 300 million connections link each voxel in the brain with every other. This pattern of connectivity is known as the functional connectome. Connectivity is often compared between experimental groups and conditions. Standard methods used to control the type 1 error rate are likely to be insensitive when comparisons are carried out across the whole connectome, due to the huge number of statistical tests involved. To address this problem, two new cluster based methods – the cluster size statistic (CSS) and cluster mass statistic (CMS) – are introduced to control the family wise error rate across all connectivity values. These methods operate within a statistical framework similar to the cluster based methods used in conventional task based fMRI. Both methods are data driven, permutation based and require minimal statistical assumptions. Here, the performance of each procedure is evaluated in a receiver operator characteristic (ROC) analysis, utilising a simulated dataset. The relative sensitivity of each method is also tested on real data: BOLD (blood oxygen level dependent) fMRI scans were carried out on twelve subjects under normal conditions and during the hypercapnic state (induced through the inhalation of 6% CO2 in 21% O2 and 73%N2). Both CSS and CMS detected significant changes in connectivity between normal and hypercapnic states. A family wise error correction carried out at the individual connection level exhibited no significant changes in connectivity. PMID:24906136

A broader understanding of care managers' attitudes of advance care planning: a concurrent nested design.

PubMed

Aultman, Julie; Baughman, Kristin R; Ludwick, Ruth

2018-05-18

To examine barriers of advance care planning (ACP) experienced by care managers (CMs) through a mixed methods approach. A concurrent nested design was used to acquire a deeper understanding of ACP, and to identify nuances between quantitative and qualitative data. Past quantitative studies on providers have identified barriers related to time, culture, knowledge, responsibility, and availability of legal documents. These barriers, and accompanying attitudes and feelings, have been taken at face value without rich qualitative data to identify under what conditions and to what extent a barrier impacts care. A two-part multisite, mixed methods study was conducted using surveys and focus groups. Surveys were completed by 458 CMs at 10 Area Agencies on Aging and 62 participated in one of 8 focus groups. Data were analyzed using a concurrent nested design with individual data analysis and a merged data approach. There were three main distinctions between the quantitative and qualitative data. First, while CMs reported on the survey that ACP was not too time consuming, focus group data revealed that time was an issue especially related to competing priorities. Second on the survey 60% of the CMS reported they had enough knowledge, but qualitative data revealed about more nuances. Last, the reported comfort levels in the quantitative data were less overt in the qualitative date where additional feelings and attitudes were revealed, e.g., frustration with families, preferences for more physician involvement. CMs reported their attitudes about ACP, clarified through a rigorous mixed methods analysis. Care managers can successfully lead ACP discussions, but require further education, resources, and team-based guidance. ACP is essential for reducing emotional, social, and financial burdens associated with health care decision-making, and CMs can positively impact ACP discussions when appropriately supported by the clinical community. The many nuances in the ACP process that we found illustrate the need for ongoing discussions, education and research on this important topic. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Prevalence of cardio-metabolic syndrome in Nigeria: a systematic review.

PubMed

Oguoma, V M; Nwose, E U; Richards, R S

2015-05-01

This is a systematic review of the distribution of cardiometabolic syndrome (CMS) in Nigeria, the clinical definitions widely used and how it affects the proposition of a national prevalence of CMS that will advise management interventions. Systematic review of literature. To present a comprehensive report of the distribution of CMS in Nigeria, extensive searches was carried out on PubMed, African Journals Online (AJOL), SCOPUS, EBSCOhost (CINAHL Plus), Google Scholar and Science Direct using terms: Nigeria, metabolic syndrome, cardio-metabolic syndrome, syndrome X, World Health Organization, International Diabetic Federation, National Cholesterol Education Program Adult Treatment Panel III, European Group for study on Insulin Resistance, American Association of Clinical Endocrinologist, American Heart Association/National Heart, Lung and Blood Institute. All published data between January 2002 and December 2013 were collated into a database. Information gathered and recorded for each source were the population sampled, age and number of population, locality, clinical definition used, longitude and latitude, and period of the study. Out of 32 studies, 9 (28.1%) adopted the WHO classification, 19 (59.4%) used the ATPIII definition, while the remaining 10 (31.3%) studies used the IDF definitions. Twenty (62.5%) were hospital-based studies on diabetic, hypertensive, HIV, asthmatic and thyroid disorder patients. The remaining 12 (37.5%) studies were population-based studies in urban, suburb and rural settings. The mean overall prevalence of CMS in Nigeria is 31.7%, 27.9% and 28.1% according to the WHO, ATPIII and IDF definitions, respectively. Most of the studies were from the Southern region. Age groups mostly studied were those from ≥35 years. The report of this review provides an essential overview on the current distribution of CMS in Nigeria. It provides an insight to direct future studies such as the need to (1) study rural communities where lifestyles are not westernized as in the urban areas, and (2) young adults, as well as (3) develop a consensus on the definition of CMS among the Sub-Saharan African populations. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Comparative analysis of mitochondrial genomes between the hau cytoplasmic male sterility (CMS) line and its iso-nuclear maintainer line in Brassica juncea to reveal the origin of the CMS-associated gene orf288.

PubMed

Heng, Shuangping; Wei, Chao; Jing, Bing; Wan, Zhengjie; Wen, Jing; Yi, Bin; Ma, Chaozhi; Tu, Jinxing; Fu, Tingdong; Shen, Jinxiong

2014-04-30

Cytoplasmic male sterility (CMS) is not only important for exploiting heterosis in crop plants, but also as a model for investigating nuclear-cytoplasmic interaction. CMS may be caused by mutations, rearrangement or recombination in the mitochondrial genome. Understanding the mitochondrial genome is often the first and key step in unraveling the molecular and genetic basis of CMS in plants. Comparative analysis of the mitochondrial genome of the hau CMS line and its maintainer line in B. juneca (Brassica juncea) may help show the origin of the CMS-associated gene orf288. Through next-generation sequencing, the B. juncea hau CMS mitochondrial genome was assembled into a single, circular-mapping molecule that is 247,903 bp in size and 45.08% in GC content. In addition to the CMS associated gene orf288, the genome contains 35 protein-encoding genes, 3 rRNAs, 25 tRNA genes and 29 ORFs of unknown function. The mitochondrial genome sizes of the maintainer line and another normal type line "J163-4" are both 219,863 bp and with GC content at 45.23%. The maintainer line has 36 genes with protein products, 3 rRNAs, 22 tRNA genes and 31 unidentified ORFs. Comparative analysis the mitochondrial genomes of the hau CMS line and its maintainer line allowed us to develop specific markers to separate the two lines at the seedling stage. We also confirmed that different mitotypes coexist substoichiometrically in hau CMS lines and its maintainer lines in B. juncea. The number of repeats larger than 100 bp in the hau CMS line (16 repeats) are nearly twice of those found in the maintainer line (9 repeats). Phylogenetic analysis of the CMS-associated gene orf288 and four other homologous sequences in Brassicaceae show that orf288 was clearly different from orf263 in Brassica tournefortii despite of strong similarity. The hau CMS mitochondrial genome was highly rearranged when compared with its iso-nuclear maintainer line mitochondrial genome. This study may be useful for studying the mechanism of natural CMS in B. juncea, performing comparative analysis on sequenced mitochondrial genomes in Brassicas, and uncovering the origin of the hau CMS mitotype and structural and evolutionary differences between different mitotypes.

Opportunistic Resource Usage in CMS

NASA Astrophysics Data System (ADS)

Kreuzer, Peter; Hufnagel, Dirk; Dykstra, D.; Gutsche, O.; Tadel, M.; Sfiligoi, I.; Letts, J.; Wuerthwein, F.; McCrea, A.; Bockelman, B.; Fajardo, E.; Linares, L.; Wagner, R.; Konstantinov, P.; Blumenfeld, B.; Bradley, D.; Cms Collaboration

2014-06-01

CMS is using a tiered setup of dedicated computing resources provided by sites distributed over the world and organized in WLCG. These sites pledge resources to CMS and are preparing them especially for CMS to run the experiment's applications. But there are more resources available opportunistically both on the GRID and in local university and research clusters which can be used for CMS applications. We will present CMS' strategy to use opportunistic resources and prepare them dynamically to run CMS applications. CMS is able to run its applications on resources that can be reached through the GRID, through EC2 compliant cloud interfaces. Even resources that can be used through ssh login nodes can be harnessed. All of these usage modes are integrated transparently into the GlideIn WMS submission infrastructure, which is the basis of CMS' opportunistic resource usage strategy. Technologies like Parrot to mount the software distribution via CVMFS and xrootd for access to data and simulation samples via the WAN are used and will be described. We will summarize the experience with opportunistic resource usage and give an outlook for the restart of LHC data taking in 2015.

Web Based Monitoring in the CMS Experiment at CERN

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

Badgett, William; Borrello, Laura; Chakaberia, Irakli

2014-09-03

The Compact Muon Solenoid (CMS) is a large and complex general purpose experiment at the CERN Large Hadron Collider (LHC), built and maintained by many collaborators from around the world. Efficient operation of the detector requires widespread and timely access to a broad range of monitoring and status information. To this end the Web Based Monitoring (WBM) system was developed to present data to users located anywhere from many underlying heterogeneous sources, from real time messaging systems to relational databases. This system provides the power to combine and correlate data in both graphical and tabular formats of interest to themore » experimenters, including data such as beam conditions, luminosity, trigger rates, detector conditions, and many others, allowing for flexibility on the user side. This paper describes the WBM system architecture and describes how the system was used during the first major data taking run of the LHC.« less

47 CFR 10.420 - Message elements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 1 2012-10-01 2012-10-01 false Message elements. 10.420 Section 10.420... Requirements § 10.420 Message elements. A CMAS Alert Message processed by a Participating CMS Provider shall include five mandatory CAP elements—Event Type; Area Affected; Recommended Action; Expiration Time (with...

47 CFR 10.420 - Message elements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 1 2011-10-01 2011-10-01 false Message elements. 10.420 Section 10.420... Requirements § 10.420 Message elements. A CMAS Alert Message processed by a Participating CMS Provider shall include five mandatory CAP elements—Event Type; Area Affected; Recommended Action; Expiration Time (with...

47 CFR 10.420 - Message elements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 1 2013-10-01 2013-10-01 false Message elements. 10.420 Section 10.420... § 10.420 Message elements. A WEA Alert Message processed by a Participating CMS Provider shall include five mandatory CAP elements—Event Type; Area Affected; Recommended Action; Expiration Time (with time...

47 CFR 10.420 - Message elements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 1 2014-10-01 2014-10-01 false Message elements. 10.420 Section 10.420... § 10.420 Message elements. A WEA Alert Message processed by a Participating CMS Provider shall include five mandatory CAP elements—Event Type; Area Affected; Recommended Action; Expiration Time (with time...

75 FR 70930 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-19

...; Title of Information Collection: Consumer Research on Public Reporting of Hospital Outpatient Measures... measures in the areas of hospital acquired conditions and healthcare associated infections, to the Hospital Compare Web site in 2011. CMS also intends to begin utilizing displays of composite measures summarizing...

42 CFR 405.1012 - When CMS or its contractors may be a party to a hearing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false When CMS or its contractors may be a party to a... Hearings § 405.1012 When CMS or its contractors may be a party to a hearing. (a) CMS and/or one or more of... unrepresented beneficiary. (b) CMS and/or the contractor(s) advises the ALJ, appellant, and all other parties...

Development of Cytoplasmic Male Sterile IR24 and IR64 Using CW-CMS/Rf17 System.

PubMed

Toriyama, Kinya; Kazama, Tomohiko

2016-12-01

A wild-abortive-type (WA) cytoplasmic male sterility (CMS) has been almost exclusively used for breeding three-line hybrid rice. Many indica cultivars are known to carry restorer genes for WA-CMS lines and cannot be used as maintainer lines. Especially elite indica cultivars IR24 and IR64 are known to be restorer lines for WA-CMS lines, and are used as male parents for hybrid seed production. If we develop CMS IR24 and CMS IR64, the combination of F1 pairs in hybrid rice breeding programs will be greatly broadened. For production of CMS lines and restorer lines of IR24 and IR64, we employed Chinese wild rice (CW)-type CMS/Restorer of fertility 17 (Rf17) system, in which fertility is restored by a single nuclear gene, Rf17. Successive backcrossing and marker-assisted selection of Rf17 succeeded to produce completely male sterile CMS lines and fully restored restorer lines of IR24 and IR64. CW-cytoplasm did not affect agronomic characteristics. Since IR64 is one of the most popular mega-varieties and used for breeding of many modern varieties, the CW-CMS line of IR64 will be useful for hybrid rice breeding.

Unique and common elements of the role of peer support in the context of traditional mental health services.

PubMed

Crane, Dushka A; Lepicki, Traci; Knudsen, Kraig

2016-09-01

The goal of this report is to clarify the unique role of peer support providers (PSPs) and define peer support as a distinct occupation in the context of traditional mental health services. A systematic methodology was used to compare roles of PSPs with those of similarly situated case managers (CMs). Key informants including 12 incumbent CMs and 11 incumbent PSPs participated in focus groups and responded to a set of prompts based on the Discovering a Curriculum (DACUM) methodology (Norton & Moser, 2014), an innovative approach to identifying and comparing duties and tasks associated with distinct occupations. Task analyses were validated through a survey of 71 CM and 29 PSP subject matter experts, including workers, supervisors, trainers, and consumers. The results revealed a variety of duties and tasks specific to the PSP occupation, particularly within the domains of empowering consumers, promoting consumers' educational growth, and supporting personal development. The results also reveal areas of overlapping responsibility between PSPs and CMs, including aspects of each role that promote consumers' development, wellness and recovery, administrative tasks, and care coordination activities. These findings may address the role ambiguity that currently challenges efforts to establish peer support as a legitimate service in the field of behavioral health. In addition, the findings demonstrate how the roles of PSPs and CMs could be synergistic in complex organizational settings. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Final Technical Report for ``Paths to Discovery at the LHC : Dark Matter and Track Triggering"

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

Hahn, Kristian

Particle Dark Matter (DM) is perhaps the most compelling and experimentally well-motivated new physics scenario anticipated at the Large Hadron Collider (LHC). The DE-SC0014073 award allowed the PI to define and pursue a path to the discovery of Dark Matter in Run-2 of the LHC with the Compact Muon Solenoid (CMS) experiment. CMS can probe regions of Dark Matter phase-space that direct and indirect detection experiments are unable to constrain. The PI’s team initiated the exploration of these regions, searching specifically for the associated production of Dark Matter with top quarks. The effort focuses on the high-yield, hadronic decays ofmore » W bosons produced in top decay, which provides the highest sensitivity to DM produced via through low-mass spin-0 mediators. The group developed identification algorithms that achieve high efficiency and purity in the selection of hadronic top decays, and analysis techniques that provide powerful signal discrimination in Run-2. The ultimate reach of new physics searches with CMS will be established at the high-luminosity LHC (HL-LHC). To fully realize the sensitivity the HL-LHC promises, CMS must minimize the impact of soft, inelastic (“pileup”) interactions on the real-time “trigger” system the experiment uses for data refinement. Charged particle trajectory information (“tracking”) will be essential for pileup mitigation at the HL-LHC. The award allowed the PI’s team to develop firmware-based data delivery and track fitting algorithms for an unprecedented, real-time tracking trigger to sustain the experiment’s sensitivity to new physics in the next decade.« less

Hydro-meteorologic assessment of October 2015 extreme precipitation event on Santee Experimental Forest Watersheds, South Carolina

Treesearch

D.M. Amatya; C.A. Harrison; C.C. Trettin

2016-01-01

The extreme precipitation event on October 3-4, 2015, likely resulting from the convergence of a persistent deep easterly flow, the continuous supply of moisture, the terrain, and the circulation associated with Hurricane Joaquin off the eastern Atlantic Coast (http://cms.met.psu. edu/sref/severe/2015/04Oct2015.pdf) resulted in extreme and prolonged flooding in many...

42 CFR 414.68 - Imaging accreditation.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Computed tomography. (iii) Nuclear medicine. (iv) Positron emission tomography. CMS-approved accreditation... if CMS takes an adverse action based on accreditation findings. (vi) Notify CMS, in writing... organization must permit its surveyors to serve as witnesses if CMS takes an adverse action based on...

42 CFR 414.68 - Imaging accreditation.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Computed tomography. (iii) Nuclear medicine. (iv) Positron emission tomography. CMS-approved accreditation... if CMS takes an adverse action based on accreditation findings. (vi) Notify CMS, in writing... organization must permit its surveyors to serve as witnesses if CMS takes an adverse action based on...

42 CFR 414.68 - Imaging accreditation.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Computed tomography. (iii) Nuclear medicine. (iv) Positron emission tomography. CMS-approved accreditation... if CMS takes an adverse action based on accreditation findings. (vi) Notify CMS, in writing... organization must permit its surveyors to serve as witnesses if CMS takes an adverse action based on...

Human embryonic and induced pluripotent stem cell-derived cardiomyocytes exhibit beat rate variability and power-law behavior.

PubMed

Mandel, Yael; Weissman, Amir; Schick, Revital; Barad, Lili; Novak, Atara; Meiry, Gideon; Goldberg, Stanislav; Lorber, Avraham; Rosen, Michael R; Itskovitz-Eldor, Joseph; Binah, Ofer

2012-02-21

The sinoatrial node is the main impulse-generating tissue in the heart. Atrioventricular conduction block and arrhythmias caused by sinoatrial node dysfunction are clinically important and generally treated with electronic pacemakers. Although an excellent solution, electronic pacemakers incorporate limitations that have stimulated research on biological pacing. To assess the suitability of potential biological pacemakers, we tested the hypothesis that the spontaneous electric activity of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) exhibit beat rate variability and power-law behavior comparable to those of human sinoatrial node. We recorded extracellular electrograms from hESC-CMs and iPSC-CMs under stable conditions for up to 15 days. The beat rate time series of the spontaneous activity were examined in terms of their power spectral density and additional methods derived from nonlinear dynamics. The major findings were that the mean beat rate of hESC-CMs and iPSC-CMs was stable throughout the 15-day follow-up period and was similar in both cell types, that hESC-CMs and iPSC-CMs exhibited intrinsic beat rate variability and fractal behavior, and that isoproterenol increased and carbamylcholine decreased the beating rate in both hESC-CMs and iPSC-CMs. This is the first study demonstrating that hESC-CMs and iPSC-CMs exhibit beat rate variability and power-law behavior as in humans, thus supporting the potential capability of these cell sources to serve as biological pacemakers. Our ability to generate sinoatrial-compatible spontaneous cardiomyocytes from the patient's own hair (via keratinocyte-derived iPSCs), thus eliminating the critical need for immunosuppression, renders these myocytes an attractive cell source as biological pacemakers.

Human renal adipose tissue induces the invasion and progression of renal cell carcinoma

PubMed Central

Campo-Verde-Arbocco, Fiorella; López-Laur, José D.; Romeo, Leonardo R.; Giorlando, Noelia; Bruna, Flavia A.; Contador, David E.; López-Fontana, Gastón; Santiano, Flavia E.; Sasso, Corina V.; Zyla, Leila E.; López-Fontana, Constanza M.; Calvo, Juan C.; Carón, Rubén W.; Creydt, Virginia Pistone

2017-01-01

We evaluated the effects of conditioned media (CMs) of human adipose tissue from renal cell carcinoma located near the tumor (hRATnT) or farther away from the tumor (hRATfT), on proliferation, adhesion and migration of tumor (786-O and ACHN) and non-tumor (HK-2) human renal epithelial cell lines. Human adipose tissues were obtained from patients with renal cell carcinoma (RCC) and CMs from hRATnT and hRATfT incubation. Proliferation, adhesion and migration were quantified in 786-O, ACHN and HK-2 cell lines incubated with hRATnT-, hRATfT- or control-CMs. We evaluated versican, adiponectin and leptin expression in CMs from hRATnT and hRATfT. We evaluated AdipoR1/2, ObR, pERK, pAkt y pPI3K expression on cell lines incubated with CMs. No differences in proliferation of cell lines was found after 24 h of treatment with CMs. All cell lines showed a significant decrease in cell adhesion and increase in cell migration after incubation with hRATnT-CMs vs. hRATfT- or control-CMs. hRATnT-CMs showed increased levels of versican and leptin, compared to hRATfT-CMs. AdipoR2 in 786-O and ACHN cells decreased significantly after incubation with hRATfT- and hRATnT-CMs vs. control-CMs. We observed a decrease in the expression of pAkt in HK-2, 786-O and ACHN incubated with hRATnT-CMs. This result could partially explain the observed changes in migration and cell adhesion. We conclude that hRATnT released factors, such as leptin and versican, could enhance the invasive potential of renal epithelial cell lines and could modulate the progression of the disease. PMID:29212223

Mitochondrial nad2 gene is co-transcripted with CMS-associated orfB gene in cytoplasmic male-sterile stem mustard (Brassica juncea).

PubMed

Yang, Jing-Hua; Zhang, Ming-Fang; Yu, Jing-Quan

2009-02-01

The transcriptional patterns of mitochondrial respiratory related genes were investigated in cytoplasmic male-sterile and fertile maintainer lines of stem mustard, Brassica juncea. There were numerous differences in nad2 (subunit 2 of NADH dehydrogenase) between stem mustard CMS and its maintainer line. One novel open reading frame, hereafter named orfB gene, was located at the downstream of mitochondrial nad2 gene in the CMS. The novel orfB gene had high similarity with YMF19 family protein, orfB in Raphanus sativus, Helianthus annuus, Nicotiana tabacum and Beta vulgaris, orfB-CMS in Daucus carota, atp8 gene in Arabidopsis thaliana, 5' flanking of orf224 in B. napus (nap CMS) and 5' flanking of orf220 gene in CMS Brassica juncea. Three copies probed by specific fragment (amplified by primers of nad2F and nad2R from CMS) were found in the CMS line following Southern blotting digested with HindIII, but only a single copy in its maintainer line. Meanwhile, two transcripts were shown in the CMS line following Northern blotting while only one transcript was detected in the maintainer line, which were probed by specific fragment (amplified by primers of nad2F and nad2R from CMS). Meanwhile, the expression of nad2 gene was reduced in CMS bud compared to that in its maintainer line. We thus suggested that nad2 gene may be co-transcripted with CMS-associated orfB gene in the CMS. In addition, the specific fragment that was amplified by primers of nad2F and nad2R just spanned partial sequences of nad2 gene and orfB gene. Such alterations in the nad2 gene would impact the activity of NADH dehydrogenase, and subsequently signaling, inducing the expression of nuclear genes involved in male sterility in this type of cytoplasmic male sterility.

Responding to GPs' information resource needs: implementation and evaluation of a complementary medicines information resource in Queensland general practice

PubMed Central

2011-01-01

Background Australian General Practitioners (GPs) are in the forefront of primary health care and in an excellent position to communicate with their patients and educate them about Complementary Medicines (CMs) use. However previous studies have demonstrated that GPs lack the knowledge required about CMs to effectively communicate with patients about their CMs use and they perceive a need for information resources on CMs to use in their clinical practice. This study aimed to develop, implement, and evaluate a CMs information resource in Queensland (Qld) general practice. Methods The results of the needs assessment survey of Qld general practitioners (GPs) informed the development of a CMs information resource which was then put through an implementation and evaluation cycle in Qld general practice. The CMs information resource was a set of evidence-based herbal medicine fact sheets. This resource was utilised by 100 Qld GPs in their clinical practice for four weeks and was then evaluated. The evaluation assessed GPs' (1) utilisation of the resource (2) perceived quality, usefulness and satisfaction with the resource and (3) perceived impact of the resource on their knowledge, attitudes, and practice of CMs. Results Ninety two out of the 100 GPs completed the four week evaluation of the fact sheets and returned the post-intervention survey. The herbal medicine fact sheets produced by this study were well accepted and utilised by Qld GPs. The majority of GPs perceived that the fact sheets were a useful resource for their clinical practice. The fact sheets improved GPs' attitudes towards CMs, increased their knowledge of those herbal medicines and improved their communication with their patients about those specific herbs. Eighty-six percent of GPs agreed that if they had adequate resources on CMs, like the herbal medicine fact sheets, then they would communicate more to their patients about their use of CMs. Conclusion Further educational interventions on CMs need to be provided to GPs to increase their knowledge of CMs and to improve their communication with patients about their CMs use. PMID:21933434

CMS results in the Combined Computing Readiness Challenge CCRC'08

NASA Astrophysics Data System (ADS)

Bonacorsi, D.; Bauerdick, L.; CMS Collaboration

2009-12-01

During February and May 2008, CMS participated to the Combined Computing Readiness Challenge (CCRC'08) together with all other LHC experiments. The purpose of this worldwide exercise was to check the readiness of the Computing infrastructure for LHC data taking. Another set of major CMS tests called Computing, Software and Analysis challenge (CSA'08) - as well as CMS cosmic runs - were also running at the same time: CCRC augmented the load on computing with additional tests to validate and stress-test all CMS computing workflows at full data taking scale, also extending this to the global WLCG community. CMS exercised most aspects of the CMS computing model, with very comprehensive tests. During May 2008, CMS moved more than 3.6 Petabytes among more than 300 links in the complex Grid topology. CMS demonstrated that is able to safely move data out of CERN to the Tier-1 sites, sustaining more than 600 MB/s as a daily average for more than seven days in a row, with enough headroom and with hourly peaks of up to 1.7 GB/s. CMS ran hundreds of simultaneous jobs at each Tier-1 site, re-reconstructing and skimming hundreds of millions of events. After re-reconstruction the fresh AOD (Analysis Object Data) has to be synchronized between Tier-1 centers: CMS demonstrated that the required inter-Tier-1 transfers are achievable within a few days. CMS also showed that skimmed analysis data sets can be transferred to Tier-2 sites for analysis at sufficient rate, regionally as well as inter-regionally, achieving all goals in about 90% of >200 links. Simultaneously, CMS also ran a large Tier-2 analysis exercise, where realistic analysis jobs were submitted to a large set of Tier-2 sites by a large number of people to produce a chaotic workload across the systems, and with more than 400 analysis users in May. Taken all together, CMS routinely achieved submissions of 100k jobs/day, with peaks up to 200k jobs/day. The achieved results in CCRC'08 - focussing on the distributed workflows - are presented and discussed.

Repeated asenapine treatment does not participate in the mild stress induced FosB/ΔFosB expression in the rat hypothalamic paraventricular nucleus neurons.

PubMed

Kiss, Alexander; Majercikova, Zuzana

2017-02-01

Effect of repeated asenapine (ASE) treatment on FosB/ΔFosB expression was studied in the hypothalamic paraventricular nucleus (PVN) of male rats exposed to chronic mild stress (CMS) for 21days. Our intention was to find out whether repeated ASE treatment for 14days may: 1) induce FosB/ΔFosB expression in the PVN; 2) activate selected PVN neuronal phenotypes, synthesizing oxytocin (OXY), vasopressin (AVP), corticoliberin (CRH) or tyrosine hydroxylase (TH); and 3) interfere with the impact of CMS. Control, ASE, CMS, and CMS+ASE treated groups were used. CMS included restraint, social isolation, crowding, swimming, and cold. From the 7th day of CMS, rats received ASE (0.3mg/kg) or saline (300μl/rat) subcutaneously, twice a day for 14days. They were sacrificed on the day 22nd (16-18h after last treatments). FosB/ΔFosB was visualized with avidin biotin peroxidase complex and OXY, AVP, CRH or TH antibodies by fluorescent dyes. Saline and ASE did not promote FosB/ΔFosB expression in the PVN. CMS and CMS+ASE elicited FosB/ΔFosB-expression in the PVN, whereas, ASE did not augment or attenuate FosB/ΔFosB induction elicited by CMS. FosB/ΔFosB-CRH occurred after CMS and CMS+ASE treatments in the PVN middle sector, while FosB/ΔFosB-AVP and FosB/ΔFosB-OXY after CMS and CMS+ASE treatments in the PVN posterior sector. FosB/ΔFosB-TH colocalization was rare. Larger FosB/ΔFosB profiles, running above the PVN, did not show any colocalizations. The study provides an anatomical/functional knowledge about an unaccented nature of prolonged ASE treatment at the level of PVN and excludes its positive or negative interplay with CMS effect. Data indicate that long-lasting ASE treatment might not act as a stressor acting at the PVN level. Copyright © 2016 Elsevier Ltd. All rights reserved.

78 FR 19269 - Medicare and Medicaid Programs; Announcement of Application From a Hospital Requesting Waiver for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-29

... Procurement Service Area AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Notice with... require the hospital to enter into an agreement with its designated Organ Procurement Organization (OPO... Organ Procurement Organizations (OPOs) are not-for-profit organizations that are responsible for the...

The elution of colistimethate sodium from polymethylmethacrylate and calcium phosphate cement beads.

PubMed

Waterman, Paige; Barber, Melissa; Weintrob, Amy C; VanBrakle, Regina; Howard, Robin; Kozar, Michael P; Andersen, Romney; Wortmann, Glenn

2012-06-01

Gram-negative bacilli resistance to all antibiotics, except for colistimethate sodium (CMS), is an emerging healthcare concern. Incorporating CMS into orthopedic cement to treat bone and soft-tissue infections due to these bacteria is attractive, but the data regarding the elution of CMS from cement are conflicting. The in vitro analysis of the elution of CMS from polymethylmethacrylate (PMMA) and calcium phosphate (CP) cement beads is reported. PMMA and CP beads containing CMS were incubated in phosphate-buffered saline and the eluate sampled at sequential time points. The inhibition of the growth of a strain of Acinetobacter baumannii complex by the eluate was measured by disk diffusion and microbroth dilution assays, and the presence of CMS in the eluate was measured by mass spectroscopy. Bacterial growth was inhibited by the eluate from both PMMA and CP beads. Mass spectroscopy demonstrated greater elution of CMS from CP beads than PMMA beads. The dose of CMS in PMMA beads was limited by failure of bead integrity. CMS elutes from both CP and PMMA beads in amounts sufficient to inhibit bacterial growth in vitro. The clinical implications of these findings require further study.

Opportunistic Resource Usage in CMS

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

Kreuzer, Peter; Hufnagel, Dirk; Dykstra, D.

2014-01-01

CMS is using a tiered setup of dedicated computing resources provided by sites distributed over the world and organized in WLCG. These sites pledge resources to CMS and are preparing them especially for CMS to run the experiment's applications. But there are more resources available opportunistically both on the GRID and in local university and research clusters which can be used for CMS applications. We will present CMS' strategy to use opportunistic resources and prepare them dynamically to run CMS applications. CMS is able to run its applications on resources that can be reached through the GRID, through EC2 compliantmore » cloud interfaces. Even resources that can be used through ssh login nodes can be harnessed. All of these usage modes are integrated transparently into the GlideIn WMS submission infrastructure, which is the basis of CMS' opportunistic resource usage strategy. Technologies like Parrot to mount the software distribution via CVMFS and xrootd for access to data and simulation samples via the WAN are used and will be described. We will summarize the experience with opportunistic resource usage and give an outlook for the restart of LHC data taking in 2015.« less

42 CFR 423.890 - Appeals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... sponsor or by CMS before notice of the reconsidered determination is made. (6) Decision of the informal written reconsideration. CMS informs the sponsor of the decision orally or through electronic mail. CMS sends a written decision to the sponsor on the sponsor's request. (7) Effect of CMS informal written...

45 CFR 150.221 - Transition to State enforcement.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for... State enforcement. (a) If CMS determines that a State for which it has assumed enforcement authority has... appropriate to return enforcement authority to the State, CMS will enter into discussions with State officials...

45 CFR 150.213 - Form and content of notice.

Code of Federal Regulations, 2010 CFR

2010-10-01

... CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for Determining... consequence of a State's failure to substantially enforce HIPAA requirements is that CMS enforces them. (d... information that the State wishes CMS to consider in making the preliminary determination described in § 150...

45 CFR 150.321 - Determining the amount of penalty-aggravating circumstances.

Code of Federal Regulations, 2010 CFR

2010-10-01

... RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement..., if there are substantial or several aggravating circumstances, CMS sets the aggregate amount of the.... CMS considers the following circumstances to be aggravating circumstances: (a) The frequency of...

45 CFR 150.343 - Notice of proposed penalty.

Code of Federal Regulations, 2010 CFR

2010-10-01

... CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement With Respect to Issuers and Non-Federal Governmental Plans-Civil Money Penalties § 150.343 Notice of proposed penalty. If CMS... penalty. The notice includes the following: (a) A description of the HIPAA requirements that CMS has...

CMS-G from Beta vulgaris ssp. maritima is maintained in natural populations despite containing an atypical cytochrome c oxidase.

PubMed

Meyer, Etienne H; Lehmann, Caroline; Boivin, Stéphane; Brings, Lea; De Cauwer, Isabelle; Bock, Ralph; Kühn, Kristina; Touzet, Pascal

2018-02-23

While mitochondrial mutants of the respiratory machinery are rare and often lethal, cytoplasmic male sterility (CMS), a mitochondrially inherited trait that results in pollen abortion, is frequently encountered in wild populations. It generates a breeding system called gynodioecy. In Beta vulgaris ssp. maritima , a gynodioecious species, we found CMS-G to be widespread across the distribution range of the species. Despite the sequencing of the mitochondrial genome of CMS-G, the mitochondrial sterilizing factor causing CMS-G is still unknown. By characterizing biochemically CMS-G, we found that the expression of several mitochondrial proteins is altered in CMS-G plants. In particular, Cox1, a core subunit of the cytochrome c oxidase (complex IV), is larger but can still assemble into complex IV. However, the CMS-G-specific complex IV was only detected as a stabilized dimer. We did not observe any alteration of the affinity of complex IV for cytochrome c ; however, in CMS-G, complex IV capacity is reduced. Our results show that CMS-G is maintained in many natural populations despite being associated with an atypical complex IV. We suggest that the modified complex IV could incur the associated cost predicted by theoretical models to maintain gynodioecy in wild populations. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Cardiometabolic syndrome and its association with education, smoking, diet, physical activity, and social support: findings from the Pennsylvania 2007 BRFSS Survey.

PubMed

Liu, Longjian; Núñez, Ana E

2010-07-01

The authors aimed to examine the prevalence of cardiometabolic syndrome (CMS) and its association with education, smoking, diet, physical activity, and social support among white, black, and Hispanic adults using data from the 2007 Pennsylvania Behavior Risk Factor Surveillance System (BRFSS) survey, the largest population-based survey in the state. The authors examined associations between CMS and associated factors cross-sectionally using univariate and multivariate methods. The study included a representative sample of 12,629 noninstitutionalized Pennsylvanians aged > or =18. Components of CMS included obesity, hypercholesterolemia, angina (as a surrogate for decreased high-density lipoprotein), prehypertension or hypertension, and prediabetes or diabetes. CMS was identified as the presence of > or =3 CMS components. The results show that the prevalence of CMS was 20.48% in blacks, followed by Hispanics (19.14%) and whites (12.26%), (P<.01). Multivariate logistic regression analyses indicated that physical inactivity, lower educational levels, smoking, daily consumption of vegetables and/or fruits <3 servings, and lack of social support were significantly associated with the odds of having CMS. In conclusion, black and Hispanic adults have a significantly higher prevalence of CMS than whites. The significant association between CMS and risk factors provides new insights in the direction of health promotion to prevent and control CMS in those who are at high risk.

The mitochondrial gene orfH79 plays a critical role in impairing both male gametophyte development and root growth in CMS-Honglian rice.

PubMed

Peng, Xiaojue; Wang, Kun; Hu, Chaofeng; Zhu, Youlin; Wang, Ting; Yang, Jing; Tong, Jiping; Li, Shaoqing; Zhu, Yingguo

2010-06-24

Cytoplasmic male sterility (CMS) has often been associated with abnormal mitochondrial open reading frames. The mitochondrial gene orfH79 is a candidate gene for causing the CMS trait in CMS-Honglian (CMS-HL) rice. However, whether the orfH79 expression can actually induce CMS in rice remains unclear. Western blot analysis revealed that the ORFH79 protein is mainly present in mitochondria of CMS-HL rice and is absent in the fertile line. To investigate the function of ORFH79 protein in mitochondria, this gene was fused to a mitochondrial transit peptide sequence and used to transform wild type rice, where its expression induced the gametophytic male sterile phenotype. In addition, excessive accumulation of reactive oxygen species (ROS) in the microspore, a reduced ATP/ADP ratio, decreased mitochondrial membrane potential and a lower respiration rate in the transgenic plants were found to be similar to those in CMS-HL rice. Moreover, retarded growth of primary and lateral roots accompanied by abnormal accumulation of ROS in the root tip was observed in both transgenic rice and CMS-HL rice (YTA). These results suggest that the expression of orfH79 in mitochondria impairs mitochondrial function, which affects the development of both male gametophytes and the roots of CMS-HL rice.

CDX2 prognostic value in stage II/III resected colon cancer is related to CMS classification.

PubMed

Pilati, C; Taieb, J; Balogoun, R; Marisa, L; de Reyniès, A; Laurent-Puig, P

2017-05-01

Caudal-type homeobox transcription factor 2 (CDX2) is involved in colon cancer (CC) oncogenesis and has been proposed as a prognostic biomarker in patients with stage II or III CC. We analyzed CDX2 expression in a series of 469 CC typed for the new international consensus molecular subtype (CMS) classification, and we confirmed results in a series of 90 CC. Here, we show that lack of CDX2 expression is only present in the mesenchymal subgroup (CMS4) and in MSI-immune tumors (CMS1) and not in CMS2 and CMS3 colon cancer. Although CDX2 expression was a globally independent prognostic factor, loss of CDX2 expression is not associated with a worse prognosis in the CMS1 group, but is highly prognostic in CMS4 patients for both relapse free and overall survival. Similarly, lack of CDX2 expression was a bad prognostic factor in MSS patients, but not in MSI. Our work suggests that combination of the consensual CMS classification and lack of CDX2 expression could be a useful marker to identify CMS4/CDX2-negative patients with a very poor prognosis. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Senp1 drives hypoxia-induced polycythemia via GATA1 and Bcl-xL in subjects with Monge’s disease

PubMed Central

Azad, Priti; Zhao, Huiwen W.; Ronen, Roy; Zhou, Dan; Poulsen, Orit; Hsiao, Yu Hsin; Bafna, Vineet

2016-01-01

In this study, because excessive polycythemia is a predominant trait in some high-altitude dwellers (chronic mountain sickness [CMS] or Monge’s disease) but not others living at the same altitude in the Andes, we took advantage of this human experiment of nature and used a combination of induced pluripotent stem cell technology, genomics, and molecular biology in this unique population to understand the molecular basis for hypoxia-induced excessive polycythemia. As compared with sea-level controls and non-CMS subjects who responded to hypoxia by increasing their RBCs modestly or not at all, respectively, CMS cells increased theirs remarkably (up to 60-fold). Although there was a switch from fetal to adult HgbA0 in all populations and a concomitant shift in oxygen binding, we found that CMS cells matured faster and had a higher efficiency and proliferative potential than non-CMS cells. We also established that SENP1 plays a critical role in the differential erythropoietic response of CMS and non-CMS subjects: we can convert the CMS phenotype into that of non-CMS and vice versa by altering SENP1 levels. We also demonstrated that GATA1 is an essential downstream target of SENP1 and that the differential expression and response of GATA1 and Bcl-xL are a key mechanism underlying CMS pathology. PMID:27821551

Senp1 drives hypoxia-induced polycythemia via GATA1 and Bcl-xL in subjects with Monge's disease.

PubMed

Azad, Priti; Zhao, Huiwen W; Cabrales, Pedro J; Ronen, Roy; Zhou, Dan; Poulsen, Orit; Appenzeller, Otto; Hsiao, Yu Hsin; Bafna, Vineet; Haddad, Gabriel G

2016-11-14

In this study, because excessive polycythemia is a predominant trait in some high-altitude dwellers (chronic mountain sickness [CMS] or Monge's disease) but not others living at the same altitude in the Andes, we took advantage of this human experiment of nature and used a combination of induced pluripotent stem cell technology, genomics, and molecular biology in this unique population to understand the molecular basis for hypoxia-induced excessive polycythemia. As compared with sea-level controls and non-CMS subjects who responded to hypoxia by increasing their RBCs modestly or not at all, respectively, CMS cells increased theirs remarkably (up to 60-fold). Although there was a switch from fetal to adult HgbA0 in all populations and a concomitant shift in oxygen binding, we found that CMS cells matured faster and had a higher efficiency and proliferative potential than non-CMS cells. We also established that SENP1 plays a critical role in the differential erythropoietic response of CMS and non-CMS subjects: we can convert the CMS phenotype into that of non-CMS and vice versa by altering SENP1 levels. We also demonstrated that GATA1 is an essential downstream target of SENP1 and that the differential expression and response of GATA1 and Bcl-xL are a key mechanism underlying CMS pathology. © 2016 Azad et al.

Enabling opportunistic resources for CMS Computing Operations

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

Hufnagel, Dirk

With the increased pressure on computing brought by the higher energy and luminosity from the LHC in Run 2, CMS Computing Operations expects to require the ability to utilize opportunistic resources resources not owned by, or a priori configured for CMS to meet peak demands. In addition to our dedicated resources we look to add computing resources from non CMS grids, cloud resources, and national supercomputing centers. CMS uses the HTCondor/glideinWMS job submission infrastructure for all its batch processing, so such resources will need to be transparently integrated into its glideinWMS pool. Bosco and parrot wrappers are used to enablemore » access and bring the CMS environment into these non CMS resources. Finally, we describe our strategy to supplement our native capabilities with opportunistic resources and our experience so far using them.« less

Enabling opportunistic resources for CMS Computing Operations

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

Hufnagel, Dick

With the increased pressure on computing brought by the higher energy and luminosity from the LHC in Run 2, CMS Computing Operations expects to require the ability to utilize “opportunistic” resources — resources not owned by, or a priori configured for CMS — to meet peak demands. In addition to our dedicated resources we look to add computing resources from non CMS grids, cloud resources, and national supercomputing centers. CMS uses the HTCondor/glideinWMS job submission infrastructure for all its batch processing, so such resources will need to be transparently integrated into its glideinWMS pool. Bosco and parrot wrappers are usedmore » to enable access and bring the CMS environment into these non CMS resources. Here we describe our strategy to supplement our native capabilities with opportunistic resources and our experience so far using them.« less

Enabling opportunistic resources for CMS Computing Operations

DOE PAGES

Hufnagel, Dirk

2015-12-23

With the increased pressure on computing brought by the higher energy and luminosity from the LHC in Run 2, CMS Computing Operations expects to require the ability to utilize opportunistic resources resources not owned by, or a priori configured for CMS to meet peak demands. In addition to our dedicated resources we look to add computing resources from non CMS grids, cloud resources, and national supercomputing centers. CMS uses the HTCondor/glideinWMS job submission infrastructure for all its batch processing, so such resources will need to be transparently integrated into its glideinWMS pool. Bosco and parrot wrappers are used to enablemore » access and bring the CMS environment into these non CMS resources. Finally, we describe our strategy to supplement our native capabilities with opportunistic resources and our experience so far using them.« less

[Recognition of psychiatric disorders with a religious content by members of the clergy of different denominations in the Netherlands].

PubMed

Noort, A; Braam, A W; van Gool, A R; Verhagen, P J; Beekman, A T F

2012-01-01

Clergy members (CMS) frequently provide support and counselling for people with psychological and psychiatric disorders. There is evidence in the literature that CMS consider themselves to be inadequately trained to recognise psychiatric disorders. To investigate to what extent CMS are able to recognise psychiatric symptoms. CMS were recruited in the south-west of the Netherlands among various denominations (Roman Catholic, strict (orthodox) Protestant, moderate Protestant and Evangelical; n = 143) by means of a regional sampling method. The participating CMS (n = 143) and a control group consisting of mental health care professionals MPHS; n = 73) evaluated four vignettes of psychiatric problems with a religious content: two were about a psychiatric disorder (a psychotic state and a psychotic depression/melancholic state), and two concerned non-psychiatric states (a spiritual/religious experience and a mourning reaction with a religious dilemma). For each vignette the respondents scored the suitability of psychiatric medication, the desirability of mental health care, the severity of the disorder and whether there was a religious or spiritual aetiology. Some CMS were able to recognise psychiatric problems almost as well as the MHPS, but among the CMS the degree of recognition varied according to the denomination. Recognition was relatively poor among Evangelical CMS, but was best among the strict Protestant CMS. Evangelical pastors and strict Protestant CMS tended to interpret the non-psychiatric states as pathological. The findings of this study emphasise the need for collaboration between MHPS and CMS and stress the importance of consultation.

78 FR 56710 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-13

... the following transmissions: OMB, Office of Information and Regulatory Affairs Attention: CMS Desk... Identifiers: CMS-10199 and CMS-10266] Agency Information Collection Activities: Submission for OMB Review... an opportunity for the public to comment on CMS' intention to collect information from the public...

42 CFR 422.510 - Termination of contract by CMS.

Code of Federal Regulations, 2012 CFR

2012-10-01

...: (1) Termination of contract by CMS. (i) CMS notifies the MA organization in writing 90 days before... organization; or (B) The MA organization experiences financial difficulties so severe that its ability to make...) of this section. (ii) CMS notifies the MA organization in writing that its contract will be...

42 CFR 422.510 - Termination of contract by CMS.

Code of Federal Regulations, 2011 CFR

2011-10-01

...: (1) Termination of contract by CMS. (i) CMS notifies the MA organization in writing 90 days before... organization; or (B) The MA organization experiences financial difficulties so severe that its ability to make...) of this section. (ii) CMS notifies the MA organization in writing that its contract will be...

42 CFR 422.510 - Termination of contract by CMS.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Termination of contract by CMS. (i) CMS notifies the MA organization in writing 90 days before the intended...; or (B) The MA organization experiences financial difficulties so severe that its ability to make...) of this section. (ii) CMS notifies the MA organization in writing that its contract will be...

42 CFR 401.108 - CMS rulings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false CMS rulings. 401.108 Section 401.108 Public Health... GENERAL ADMINISTRATIVE REQUIREMENTS Confidentiality and Disclosure § 401.108 CMS rulings. (a) After... regulations, but which has been adopted by CMS as having precedent, may be published in the Federal Register...

45 CFR 150.319 - Determining the amount of the penalty-mitigating circumstances.

Code of Federal Regulations, 2010 CFR

2010-10-01

... RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement... guidelines for taking into account the factors listed in § 150.317, CMS considers the following: (a) Record... noncompliance without notice from CMS and voluntarily reported that noncompliance, provided that the responsible...

42 CFR 401.625 - Effect of CMS claims collection decisions on appeals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Effect of CMS claims collection decisions on... Compromise § 401.625 Effect of CMS claims collection decisions on appeals. Any action taken under this..., is not an initial determination for purposes of CMS appeal procedures. ...

42 CFR 403.248 - Administrative review of CMS determinations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Administrative review of CMS determinations. 403... Certification Program: General Provisions § 403.248 Administrative review of CMS determinations. (a) This section provides for administrative review if CMS determines— (1) Not to certify a policy; or (2) That a...

78 FR 67149 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-08

... Identifier: CMS-R-216] Agency Information Collection Activities: Proposed Collection; Comment Request AGENCY... & Medicaid Services (CMS) is announcing an opportunity for the public to comment on CMS' intention to collect... accepting comments. 2. By regular mail. You may mail written comments to the following address: CMS, Office...

How Patronage Politics Undermines Parental Participation and Accountability: Community-Managed Schools in Honduras and Guatemala

ERIC Educational Resources Information Center

Altschuler, Daniel

2013-01-01

This article shows how patronage politics affects a popular international education model: community-managed schools (CMS). Focusing on Honduras's CMS initiative, PROHECO (Programa Hondureno de Educacion Comunitaria), I demonstrate how patronage can undermine CMS accountability. Whereas supporters argue that CMS increases accountability, partisan…

42 CFR 493.571 - Disclosure of accreditation, State and CMS validation inspection results.

Code of Federal Regulations, 2013 CFR

2013-10-01

... validation inspection results. 493.571 Section 493.571 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Program § 493.571 Disclosure of accreditation, State and CMS validation inspection results. (a... licensure program, in accordance with State law. (c) CMS validation inspection results. CMS may disclose the...

42 CFR 493.571 - Disclosure of accreditation, State and CMS validation inspection results.

Code of Federal Regulations, 2011 CFR

2011-10-01

... validation inspection results. 493.571 Section 493.571 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Program § 493.571 Disclosure of accreditation, State and CMS validation inspection results. (a... licensure program, in accordance with State law. (c) CMS validation inspection results. CMS may disclose the...

42 CFR 493.571 - Disclosure of accreditation, State and CMS validation inspection results.

Code of Federal Regulations, 2012 CFR

2012-10-01

... validation inspection results. 493.571 Section 493.571 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Program § 493.571 Disclosure of accreditation, State and CMS validation inspection results. (a... licensure program, in accordance with State law. (c) CMS validation inspection results. CMS may disclose the...

42 CFR 493.571 - Disclosure of accreditation, State and CMS validation inspection results.

Code of Federal Regulations, 2010 CFR

2010-10-01

... validation inspection results. 493.571 Section 493.571 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Program § 493.571 Disclosure of accreditation, State and CMS validation inspection results. (a... licensure program, in accordance with State law. (c) CMS validation inspection results. CMS may disclose the...

42 CFR 493.571 - Disclosure of accreditation, State and CMS validation inspection results.

Code of Federal Regulations, 2014 CFR

2014-10-01

... validation inspection results. 493.571 Section 493.571 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Program § 493.571 Disclosure of accreditation, State and CMS validation inspection results. (a... licensure program, in accordance with State law. (c) CMS validation inspection results. CMS may disclose the...

The Medicare Health Outcomes Survey program: overview, context, and near-term prospects.

PubMed

Jones, Nathaniel; Jones, Stephanie L; Miller, Nancy A

2004-07-12

In 1996, the Centers for Medicare & Medicaid Services (CMS) initiated the Medicare Health Outcomes Survey (HOS). It is the first national survey to measure the quality of life and functional health status of Medicare beneficiaries enrolled in managed care. The program seeks to gather valid and reliable health status data in Medicare managed care for use in quality improvement activities, public reporting, plan accountability and improving health outcomes based on competition. The context that led to the development of the HOS was formed by the convergence of the following factors: 1) a recognized need to monitor the performance of managed care plans, 2) technical expertise and advancement in the areas of quality measurement and health outcomes assessment, 3) the existence of a tested functional health status assessment tool (SF-36)1, which was valid for an elderly population, 4) CMS leadership, and 5) political interest in quality improvement. Since 1998, there have been six baseline surveys and four follow up surveys. CMS, working with its partners, performs the following tasks as part of the HOS program: 1) Supports the technical/scientific development of the HOS measure, 2) Certifies survey vendors, 3) Collects Health Plan Employer Data and Information Set(HEDIS)2 HOS data, 4) Cleans, scores, and disseminates annual rounds of HOS data, public use files and reports to CMS, Quality Improvement Organizations (QIOs), Medicare+Choice Organizations (M+COs), and other stakeholders, 5) Trains M+COs and QIOs in the use of functional status measures and best practices for improving care, 6) Provides technical assistance to CMS, QIOs, M+COs and other data users, and 7) Conducts analyses using HOS data to support CMS and HHS priorities.CMS has recently sponsored an evaluation of the HOS program, which will provide the information necessary to enhance the future administration of the program. Information collected to date reveals that the HOS program is a valuable tool that provides a rich set of data that is useful for quality monitoring and improvement efforts. To enhance the future of the HOS program, many stakeholders recommend the implementation of incentives to encourage the use of the data, while others identify the need to monitor the health status of plan disenrollees.Overall, the HOS program represents an important vehicle for collecting outcomes data from Medicare beneficiaries. The new Medicare Prescription Drug, Improvement, and Modernization Act (2003) mandates the collection and use of data for outcomes measurement. Consequently, it is important to improve HOS to most effectively meet the mandate.

[Preparation of vanilline cross-linked rhBMP-2/chitosan microspheres and its effect on mesenchymal stem cells].

PubMed

Wu, Gui; Wang, Hai; Qiu, Guixing; Yu, Xin; Su, Xinlin; Ma, Pei; Yin, Bo; Wu, Zhihong

2015-06-02

To prepare rhBMP-2/chitosan microspheres (rhBMP-2 CMs) with vanilline as a cross-linking reagent and study the biocompatibility and drug release characteristic of microspheres in vitro. Emulsion cross-linking method was utilized to prepare rhBMP-2 CMs, Scanning electron microscope (SEM) was used to observe the microstructure of microspheres.Leaching solution of microspheres and blank culture medium were designated as experimental and control groups respectively. Both groups were cultured with human mesenchymal stem cells (hMSCs) to determine its cytotoxicity and its effect on the proliferation of hMSCs. Dynamic immersion method was used to examine the in vitro release characteristic of rhBMP-2. And the alkaline phosphatase (ALP) activity of hMSCs was determined to reveal the bioactivity of released rhBMP-2. The rhBMP-2 CMs were spherical under SEM.After treating with leaching solution for 24 and 48 h, there was no inter-group statistical difference in optical density (OD) values at both timepoints (24 h:0.72 ± 0.07 vs 0.73 ± 0.05, P > 0.05; 48 h:1.19 ± 0.11 vs 1.27 ± 0.06, P > 0.05). After culturing with leaching solution for 1, 3 and 7 days, the number of cells increased with time for both groups. And the OD values were not statistically different at each timepoint. Five milligram rhBMP-2 CMs soaked for 19 days with a gradual release of rhBMP-2. The concentration of rhBMP-2 was 216.1 ± 20.0 ng/ml at Day 19. At Days 3 and 7, the ALP activities of hMSCs were (0.50 ± 0.07) and (0.68 ± 0.06) µmol pNPP·min⁻¹·mg⁻¹ protein respectively and both were higher than that of blank culture medium group (0.14 ± 0.01) (P < 0.05). With an excellent biocompatibility, rhBMP-2 CMs may be an ideal carrier for control-released rhBMP-2 and encapsulated rhBMP-2 remains bioactive.

Registration of cytoplasmic male-sterile oilseed sunflower genetic stocks CMS GIG2 and CMS GIG2-RV, and fertility restoration lines RF GIG2-MAX 1631 and RF GIG2-MAX 1631-RV

USDA-ARS?s Scientific Manuscript database

Two cytoplasmic male-sterile (CMS) oilseed sunflower (Helianthus annuus L.) genetic stocks, CMS GIG2 (Reg. No. xxx, PI xxxx), and CMS GIG2-RV (Reg. No. xxx, PI xxxx), and corresponding fertility restoration lines RF GIG2-MAX 1631 (Reg. No. xxx, PI xxxx) and RF GIG2-MAX 1631-RV (Reg. No. xxx, PI xxx...

CMS Nonpayment Policy, Quality Improvement, and Hospital-Acquired Conditions: An Integrative Review.

PubMed

Bae, Sung-Heui

This integrative review synthesized evidence on the consequences of the Centers for Medicare & Medicaid Services (CMS) nonpayment policy on quality improvement initiatives and hospital-acquired conditions. Fourteen articles were included. This review presents strong evidence that the CMS policy has spurred quality improvement initiatives; however, the relationships between the CMS policy and hospital-acquired conditions are inconclusive. In future research, a comprehensive model of implementation of the CMS nonpayment policy would help us understand the effectiveness of this policy.

Construction and beam-tests of silicon-tungsten prototype modules for the CMS High Granularity Calorimeter for HL-LHC

NASA Astrophysics Data System (ADS)

Quast, Thorben

2018-02-01

As part of its HL-LHC upgrade program, CMS is developing a High Granularity Calorimeter (HGCAL) to replace the existing endcap calorimeters. The HGCAL will be realised as a sampling calorimeter, including an electromagnetic compartment comprising 28 layers of silicon pad detectors with pad areas of 0.5-1.0 cm2 interspersed with absorbers. Prototype modules, based on 6-inch hexagonal silicon pad sensors with 128 channels, have been constructed and include many of the features required for this challenging detector. In 2016, beam tests of sampling configurations made from these modules have been conducted both at FNAL and at CERN using the Skiroc2 front-end ASIC (designed by the CALICE collaboration for ILC). In 2017, the setup has been extended with CALICE's AHCAL prototype, a scinitillator based sampling calorimeter, and it was further tested in dedicated beam tests at CERN. There, the new Skiroc2-CMS front-end ASIC was used for the first time. We highlight final results from our studies in 2016, including position resolution as well as precision timing-measurements. Furthermore, the extended setup in 2017 is discussed and first results from beam tests with electrons and pions are shown.

Simulation of the shape and size of casein micelles in a film state.

PubMed

Gebhardt, Ronald; Kulozik, Ulrich

2014-04-01

Size fractionated casein micelles (CMs) form homogeneous films in which they are densely packed. The lateral size of CMs in films can be well resolved by surface-sensitive methods, but the estimation of their heights is still a challenge. We show that height information can be obtained from scattering patterns of GISAXS experiments on highly ordered casein films. We use an elastic scattering approach within the distorted wave Born approximation (DWBA) to simulate for the first time the two-dimensional intensity distribution of a GISAXS experiment of the CM near their critical angle. The model which fits the GISAXS data best considers an ellipsoidal form factor for the CM and an arrangement on a hexagonal lattice. Our results indicate that during film formation the spherical solution structure of CMs becomes compressed in the direction perpendicular to the film surface. In the film state, the micelles assume an oblate ellipsoidal shape with an aspect ratio of 1.9. Hence, their surface and contact area to the surrounding increases. As a result, the density of κ-casein on the micellar surface decreases, which could influence the functional properties of coatings and films.

Human-In-The-Loop Investigation of Interoperability Between Terminal Sequencing and Spacing, Automated Terminal Proximity Alert, and Wake-Separation Recategorization

NASA Technical Reports Server (NTRS)

Callantine, Todd J.; Bienert, Nancy; Borade, Abhay; Gabriel, Conrad; Gujral, Vimmy; Jobe, Kim; Martin, Lynne; Omar, Faisal; Prevot, Thomas; Mercer, Joey

2016-01-01

A human-in-the-loop simulation study addressed terminal-area controller-workstation interface variations for interoperability between three new capabilities being introduced by the FAA. The capabilities are Terminal Sequencing and Spacing (TSAS), Automated Terminal Proximity Alert (ATPA), and wake-separation recategorization, or 'RECAT.' TSAS provides controllers with Controller-Managed Spacing (CMS) tools, including slot markers, speed advisories, and early/late indications, together with runway assignments and sequence numbers. ATPA provides automatic monitor, warning, and alert cones to inform controllers about spacing between aircraft on approach. ATPA cones are sized according to RECAT, an improved method of specifying wake-separation standards. The objective of the study was to identify potential issues and provide recommendations for integrating TSAS with ATPA and RECAT. Participants controlled arrival traffic under seven different display configurations, then tested an 'exploratory' configuration developed with participant input. All the display conditions were workable and acceptable, but controllers strongly preferred having the CMS tools available on Feeder positions, and both CMS tools and ATPA available on Final positions. Controllers found the integrated systems favorable and liked being able to tailor configurations to individual preferences.

CMS users data management service integration and first experiences with its NoSQL data storage

NASA Astrophysics Data System (ADS)

Riahi, H.; Spiga, D.; Boccali, T.; Ciangottini, D.; Cinquilli, M.; Hernàndez, J. M.; Konstantinov, P.; Mascheroni, M.; Santocchia, A.

2014-06-01

The distributed data analysis workflow in CMS assumes that jobs run in a different location to where their results are finally stored. Typically the user outputs must be transferred from one site to another by a dedicated CMS service, AsyncStageOut. This new service is originally developed to address the inefficiency in using the CMS computing resources when transferring the analysis job outputs, synchronously, once they are produced in the job execution node to the remote site. The AsyncStageOut is designed as a thin application relying only on the NoSQL database (CouchDB) as input and data storage. It has progressed from a limited prototype to a highly adaptable service which manages and monitors the whole user files steps, namely file transfer and publication. The AsyncStageOut is integrated with the Common CMS/Atlas Analysis Framework. It foresees the management of nearly nearly 200k users' files per day of close to 1000 individual users per month with minimal delays, and providing a real time monitoring and reports to users and service operators, while being highly available. The associated data volume represents a new set of challenges in the areas of database scalability and service performance and efficiency. In this paper, we present an overview of the AsyncStageOut model and the integration strategy with the Common Analysis Framework. The motivations for using the NoSQL technology are also presented, as well as data design and the techniques used for efficient indexing and monitoring of the data. We describe deployment model for the high availability and scalability of the service. We also discuss the hardware requirements and the results achieved as they were determined by testing with actual data and realistic loads during the commissioning and the initial production phase with the Common Analysis Framework.

Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation: I. Reduced flow velocity in the left atrial appendage (The Stroke Prevention in Atrial Fibrillation [SPAF-III] study).

PubMed

Goldman, M E; Pearce, L A; Hart, R G; Zabalgoitia, M; Asinger, R W; Safford, R; Halperin, J L

1999-12-01

Stroke associated with atrial fibrillation (AF) is mainly due to embolism of thrombus formed during stasis of blood in the left atrial appendage (LAA). Pathophysiologic correlates of appendage flow velocity as assessed by transesophageal echocardiography (TEE) in patients with AF have not been defined. To evaluate the hypothesis that reduced velocity is associated with spontaneous echocardiographic contrast and thrombus in the LAA and with clinical embolic events, we measured LAA flow velocity by TEE in 721 patients with nonvalvular AF entering the Stroke Prevention in Atrial Fibrillation (SPAF-III) study. Patient features, TEE findings, and subsequent cardioembolic events were correlated with velocity by multivariate analysis. Patients in AF during TEE displayed lower peak antegrade (emptying) flow velocity (Anu(p)) than those with intermittent AF in sinus rhythm during TEE (33 cm/s vs 61 cm/s, respectively, P <.0001). Anu(p) < 20 cm/s was associated with dense spontaneous echocardiographic contrast (P <.001), appendage thrombus (P <.01), and subsequent cardioembolic events (P <.01). Independent predictors of Anu(p) < 20 cm/s included age (P =.009), systolic blood pressure (P <.001), sustained AF (P =.01), ischemic heart disease (P =.01), and left atrial area (P =.04). Multivariate analysis found both Anu(p) <20 cm/s (relative risk 2.6, P =.02) and clinical risk factors (relative risk 3.3, P =.002) independently associated with LAA thrombus. LAA Anu(p) is reduced in AF and associated with spontaneous echocardiographic contrast, appendage thrombus, and cardioembolic stroke. Systolic hypertension and aortic atherosclerosis, independent clinical predictors of stroke in patients with AF, also correlated with LAA Anu(p). Our results support the role of reduced LAA Anu(p) in the generation of stasis, thrombus formation, and embolism in patients with AF, although other mechanisms also contribute to stroke.

Oral pharmacokinetics of baicalin, wogonoside, oroxylin A 7-O-β-d-glucuronide and their aglycones from an aqueous extract of Scutellariae Radix in the rat.

PubMed

Cai, Yu; Li, Sai; Li, Ting; Zhou, Ruina; Wai, Alfred Tai-Seng; Yan, Ru

2016-07-15

Scutellariae Radix (SR) has been extensively prescribed in folk medicines due to its notable beneficial activities. The flavonoid glucuronides baicalin (BG), wogonoside (WG), oroxylin A 7-O-β-d-glucuronide (OG) and their aglycones baicalein, wogonin and oroxylin A, are the main components of the herb. So far, majority of previous studies failed to report the pharmacokinetics and none offered an explanation for the systemic exposures of these six flavonoids when the herbal extract was orally administered. In this study, when a SR extract was orally dosed to rats (800mg/kg, equivalent to BG 324.80, WG 124.00, OG 43.04, baicalein 25.36, wogonin 24.40, and oroxylin A 5.79mg/kg), all six flavonoids were detectable throughout the experimental period (48h) using an LC-MS/MS method with the Cmax and AUC0-48h of the glucuronides 10-130 times that of respective aglycones. As the lowest among the three glucuronides in the herb, OG was the most abundant in vivo, while the systemic exposure of wogonin was the highest amongst the three aglycones. The dose-normalized AUC0-48h descended in orders of OG/oroxylin A, WG/wogonin and BG/baicalein. Two di-conjugates of baicalein (BG glucuronide and BG glucoside), two BG isomers (minor BM1 and major BM2), and one WG isomer (wogonin 5-O-glucuronide) were detected in rat plasma. Semi-quantitation of the isomers with peak area data revealed that the AUPs (area under peak area ratio-time curves) of BG isomers were ∼3 times that of BG, yet the AUP of wogonin 5-O-glucuronide was only one seventh of WG. BM2, tentatively assigned as baicalein 6-O-glucuronide, was formed from both microbial isomerization of BG and hepatic glucuronidation of baicalein. Wogonin 5-O-glucuronide was only formed in hepatic glucuronidation of wogonin. Demethylated wogonin was observed in gut bacteria, offering an optional origin of BM1 apart from baicalein glucuronidation. Microbial isomerization of BG and extensive hepatic glucuronidation of baicalein to form BM2as well as a poorer intestinal permeability of baicalein (Papp×10(-6)cm/s) should account for the lower systemic exposures of BG and baicalein. Faster microbial hydrolysis of WG, high intestinal permeability (Papp×10(-5)cm/s) and less hepatic glucuronidation of wogonin explain the relatively high systemic exposure of wogonin. Sole microbial deglycosylation of OG, high intestinal permeability (Papp×10(-5)cm/s) and extensive hepatic glucuronidation of oroxylin A supported the highest systemic exposure of OG. Taken together, the oral kinetics of six flavonoid glucuronides and aglycones in the SR extract were simultaneously obtained. Microbial conversion, intestinal epithelial permeability and hepatic glucuronidation are determinant factors for their systemic exposures. Copyright © 2015 Elsevier B.V. All rights reserved.

CMS Centres Worldwide - a New Collaborative Infrastructure

NASA Astrophysics Data System (ADS)

Taylor, Lucas

2011-12-01

The CMS Experiment at the LHC has established a network of more than fifty inter-connected "CMS Centres" at CERN and in institutes in the Americas, Asia, Australasia, and Europe. These facilities are used by people doing CMS detector and computing grid operations, remote shifts, data quality monitoring and analysis, as well as education and outreach. We present the computing, software, and collaborative tools and videoconferencing systems. These include permanently running "telepresence" video links (hardware-based H.323, EVO and Vidyo), Webcasts, and generic Web tools such as CMS-TV for broadcasting live monitoring and outreach information. Being Web-based and experiment-independent, these systems could easily be extended to other organizations. We describe the experiences of using CMS Centres Worldwide in the CMS data-taking operations as well as for major media events with several hundred TV channels, radio stations, and many more press journalists simultaneously around the world.

Relations between the Test of Variables of Attention (TOVA) and the Children's Memory Scale (CMS).

PubMed

Riccio, Cynthia A; Garland, Beth H; Cohen, Morris J

2007-09-01

There is considerable overlap in the constructs of attention and memory. The objective of this study was to examine the relationship between the Test of Variables of Attention (TOVA), a measure of attention, to components of memory and learning as measured by the Children's Memory Scale (CMS). Participants (N = 105) were consecutive referrals to an out-patient facility, generally for learning or behavior problems, who were administered both the TOVA and the CMS. Significant correlations were found between the omissions score on the TOVA and subscales of the CMS. TOVA variability and TOVA reaction time correlated significantly with subscales of the CMS as well. TOVA commission errors did not correlate significantly with any CMS Index. Although significant, the correlation coefficients indicate that the CMS and TOVA are measuring either different constructs or similar constructs but in different ways. As such, both measures may be useful in distinguishing memory from attention problems.

Pool Formation in Boulder-Bed Streams: Implications From 1-D and 2-D Numerical Modeling

NASA Astrophysics Data System (ADS)

Harrison, L. R.; Keller, E. A.

2003-12-01

In mountain rivers of Southern California, boulder-large roughness elements strongly influence flow hydraulics and pool formation and maintenance. In these systems, boulders appear to control the stream morphology by converging flow and producing deep pools during channel forming discharges. Our research goal is to develop quantitative relationships between boulder roughness elements, temporal patterns of scour and fill, and geomorphic processes that are important in producing pool habitat. The longitudinal distribution of shear stress, unit stream power and velocity were estimated along a 48 m reach on Rattlesnake Creek, using the HEC-RAS v 3.0 and River 2-D numerical models. The reach has an average slope of 0.02 and consists of a pool-riffle sequence with a large boulder constriction directly above the pool. Model runs were performed for a range of stream discharges to test if scour and fill thresholds for pool and riffle environments could be identified. Results from the HEC-RAS simulations identified that thresholds in shear stress, unit stream power and mean velocity occur above a discharge of 5.0 cms. Results from the one-dimensional analysis suggest that the reversal in competency is likely due to changes in cross-sectional width at varying flows. River 2-D predictions indicated that strong transverse velocity gradients were present through the pool at higher modeled discharges. At a flow of 0.5 cms (roughly 1/10th bankfull discharge), velocities are estimated at 0.6 m/s and 1.3 m/s for the pool and riffle, respectively. During discharges of 5.15 cms (approximate bankfull discharge), the maximum velocity in the pool center increased to nearly 3.0 m/s, while the maximum velocity over the riffle is estimated at approximately 2.5 cms. These results are consistent with those predicted by HEC-RAS, though the reversal appears to be limited to a narrow jet that occurs through the pool head and pool center. Model predictions suggest that the velocity reversal is produced by a boulder-bedrock constriction that rapidly decreases the channel width above the pool by roughly 25 percent. The width constriction creates highly turbulent flow capable of scouring bed material through the pool. The high velocity core that is produced through the pool center appears to be enhanced by the formation of a large eddy directly below the boulder. Values of unit stream power and shear stress indicate that the pool exit is an area of deposition of bed material due to a decrease in tractive force. The presence of a strong transverse velocity gradient suggests that only a portion of the flow is responsible for scouring bed material. After we eliminate the dead water zone, the lowest five percent of the velocity range, patterns of effective width between pools and riffles begin to emerge. The ratio of flow width between adjacent pools and riffles is one measure of flow convergence. At a discharge of 0.5 cms, the ratio of effective width between pools and riffles is roughly 1:1, implying that there is uniform flow with little flow convergence. At a discharge of 5.15 cms the width ratio between the pool and riffle is about 1:3, demonstrating the strong convergent flow patterns at the pool head. The observed effective width relationship suggests that when considering restoration designs, boulders should be placed in areas that replicate natural convergence and divergence patterns in order to maximize pool area and depth.

42 CFR 423.509 - Termination of contract by CMS.

Code of Federal Regulations, 2014 CFR

2014-10-01

...: (1) Termination of contract by CMS. (i) CMS notifies the Part D plan sponsor in writing at least 45... experiences financial difficulties so severe that its ability to make necessary health services available is...) CMS notifies the Part D plan sponsor in writing that its contract will be terminated on a date...

77 FR 70445 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

...-wide set of credentials and single sign-on capability for multiple CMS applications. In order to prove... and answers); 4. Provide the user a single sign-on, federated CMS EIDM ID and Password; 5... Terms of Service and CMS Privacy Statement on the Web. Form Numbers: CMS-10452 (OCN: 0938-New...

Increasing Honest Responding on Cognitive Distortions in Child Molesters: The Bogus Pipeline Procedure

ERIC Educational Resources Information Center

Gannon, Theresa A.

2006-01-01

Professionals conclude that child molesters (CMs) hold offense-supportive beliefs (or cognitive distortions) from CMs' questionnaire responses. Because questionnaires are easily faked, we asked 32 CMs to complete a cognitive distortion scale under standard conditions (Time 1). A week later (Time 2), the same CMs completed the scale again. This…

42 CFR 417.801 - Agreements between CMS and health care prepayment plans.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Agreements between CMS and health care prepayment... CMS and health care prepayment plans. (a) General requirement. (1) In order to participate and receive... written agreement with CMS. (2) An existing group practice prepayment plan (GPPP) that continues as an...

45 CFR 150.347 - Failure to request a hearing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement With Respect to Issuers and....343, CMS may assess the proposed civil money penalty, a less severe penalty, or a more severe penalty. CMS notifies the responsible entity in writing of any penalty that has been assessed and of the means...

42 CFR 411.379 - When CMS accepts a request.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false When CMS accepts a request. 411.379 Section 411.379... Physicians and Entities Furnishing Designated Health Services § 411.379 When CMS accepts a request. (a) Upon receiving a request for an advisory opinion, CMS promptly makes an initial determination of whether the...

42 CFR 405.1834 - CMS reviewing official procedure.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false CMS reviewing official procedure. 405.1834 Section... Determinations and Appeals § 405.1834 CMS reviewing official procedure. (a) Scope. A provider that is a party to... Administrator by a designated CMS reviewing official who considers whether the decision of the intermediary...

42 CFR 457.1003 - CMS review of waiver requests.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false CMS review of waiver requests. 457.1003 Section 457.1003 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Waivers: General Provisions § 457.1003 CMS review of waiver requests. CMS will review the waiver requests...

45 CFR 150.301 - General rule regarding the imposition of civil money penalties.

Code of Federal Regulations, 2010 CFR

2010-10-01

... REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS... to CMS's enforcement authority under § 150.101(b)(2), or any non-Federal governmental plan (or employer that sponsors a non-Federal governmental plan) that is subject to CMS's enforcement authority...

42 CFR 421.114 - Assignment and reassignment of providers by CMS.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Assignment and reassignment of providers by CMS. 421.114 Section 421.114 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH... Assignment and reassignment of providers by CMS. CMS may assign or reassign any provider to any intermediary...

45 CFR 150.209 - Verification of exhaustion of remedies and contact with State officials.

Code of Federal Regulations, 2010 CFR

2010-10-01

... REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS... § 150.209 Verification of exhaustion of remedies and contact with State officials. If CMS receives a complaint or other information indicating that a State is failing to enforce HIPAA requirements, CMS...

Sleep disturbances in long-term immigrants with chronic mountain sickness: a comparison with healthy immigrants at high altitude.

PubMed

Guan, Wei; Ga, Qin; Li, Rong; Bai, Zhen-Zhong; Wuren, Tana; Wang, Jin; Yang, Ying-Zhong; Li, Yu-Hong; Ge, Ri-Li

2015-01-15

The aim of this study was to examine sleep disturbances in patients with chronic mountain sickness (CMS). The sleep of 14 patients with CMS and 11 healthy controls with or without sleep disorders (control N: without sleep disorders; control D: with sleep disorders) was studied by polysomnography. Hypopnea was the sleep disorder most commonly suffered by CMS patients and control D subjects. No major differences were observed in sleep structure between CMS and control groups, with the exception of shorter rapid eye movement latency in controls and increased deep non-rapid eye movement in the control N group. Periodic breathing was observed in only two study participants, one each in the CMS and control D groups. The level of saturated oxygen was significantly lower in the CMS group during sleep than the control groups (P<0.05). CMS scores were positively correlated with the apnea-hypopnea index, and negatively correlated with saturated oxygen levels. These results demonstrate that sleep disorders and nocturnal hypoxia are important in the development of CMS. Copyright © 2014 Elsevier B.V. All rights reserved.

CMS Analysis School Model

NASA Astrophysics Data System (ADS)

Malik, S.; Shipsey, I.; Cavanaugh, R.; Bloom, K.; Chan, Kai-Feng; D'Hondt, J.; Klima, B.; Narain, M.; Palla, F.; Rolandi, G.; Schörner-Sadenius, T.

2014-06-01

To impart hands-on training in physics analysis, CMS experiment initiated the concept of CMS Data Analysis School (CMSDAS). It was born over three years ago at the LPC (LHC Physics Centre), Fermilab and is based on earlier workshops held at the LPC and CLEO Experiment. As CMS transitioned from construction to the data taking mode, the nature of earlier training also evolved to include more of analysis tools, software tutorials and physics analysis. This effort epitomized as CMSDAS has proven to be a key for the new and young physicists to jump start and contribute to the physics goals of CMS by looking for new physics with the collision data. With over 400 physicists trained in six CMSDAS around the globe, CMS is trying to engage the collaboration in its discovery potential and maximize physics output. As a bigger goal, CMS is striving to nurture and increase engagement of the myriad talents, in the development of physics, service, upgrade, education of those new to CMS and the career development of younger members. An extension of the concept to the dedicated software and hardware schools is also planned, keeping in mind the ensuing upgrade phase.

Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

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

Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C.

One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation.more » - Highlights: • Dexamethasone accelerates Ca{sup 2+} transient decay in hESC-CMs. • Dexamethasone enhances SERCA and NCX function in hESC-CMs. • Dexamethasone increases force of contraction and sarcomere length in hESC-CMs. • Dexamethasone does not alter I{sub Ca,L} and action potential characteristics in hESC-CMs.« less

Pharmacokinetics of Colistin Methansulphonate (CMS) and Colistin after CMS Nebulisation in Baboon Monkeys.

PubMed

Marchand, Sandrine; Bouchene, Salim; de Monte, Michèle; Guilleminault, Laurent; Montharu, Jérôme; Cabrera, Maria; Grégoire, Nicolas; Gobin, Patrice; Diot, Patrice; Couet, William; Vecellio, Laurent

2015-10-01

The objective of this study was to compare two different nebulizers: Eflow rapid® and Pari LC star® by scintigraphy and PK modeling to simulate epithelial lining fluid concentrations from measured plasma concentrations, after nebulization of CMS in baboons. Three baboons received CMS by IV infusion and by 2 types of aerosols generators and colistin by subcutaneous infusion. Gamma imaging was performed after nebulisation to determine colistin distribution in lungs. Blood samples were collected during 9 h and colistin and CMS plasma concentrations were measured by LC-MS/MS. A population pharmacokinetic analysis was conducted and simulations were performed to predict lung concentrations after nebulization. Higher aerosol distribution into lungs was observed by scintigraphy, when CMS was nebulized with Pari LC® star than with Eflow Rapid® nebulizer. This observation was confirmed by the fraction of CMS deposited into the lung (respectively 3.5% versus 1.3%).CMS and colistin simulated concentrations in epithelial lining fluid were higher after using the Pari LC star® than the Eflow rapid® system. A limited fraction of CMS reaches lungs after nebulization, but higher colistin plasma concentrations were measured and higher intrapulmonary colistin concentrations were simulated with the Pari LC Star® than with the Eflow Rapid® system.

A Population WB-PBPK Model of Colistin and its Prodrug CMS in Pigs: Focus on the Renal Distribution and Excretion.

PubMed

Viel, Alexis; Henri, Jérôme; Bouchène, Salim; Laroche, Julian; Rolland, Jean-Guy; Manceau, Jacqueline; Laurentie, Michel; Couet, William; Grégoire, Nicolas

2018-03-12

The objective was the development of a whole-body physiologically-based pharmacokinetic (WB-PBPK) model for colistin, and its prodrug colistimethate sodium (CMS), in pigs to explore their tissue distribution, especially in kidneys. Plasma and tissue concentrations of CMS and colistin were measured after systemic administrations of different dosing regimens of CMS in pigs. The WB-PBPK model was developed based on these data according to a non-linear mixed effect approach and using NONMEM software. A detailed sub-model was implemented for kidneys to handle the complex disposition of CMS and colistin within this organ. The WB-PBPK model well captured the kinetic profiles of CMS and colistin in plasma. In kidneys, an accumulation and slow elimination of colistin were observed and well described by the model. Kidneys seemed to have a major role in the elimination processes, through tubular secretion of CMS and intracellular degradation of colistin. Lastly, to illustrate the usefulness of the PBPK model, an estimation of the withdrawal periods after veterinary use of CMS in pigs was made. The WB-PBPK model gives an insight into the renal distribution and elimination of CMS and colistin in pigs; it may be further developed to explore the colistin induced-nephrotoxicity in humans.

The Particle Physics Playground website: tutorials and activities using real experimental data

NASA Astrophysics Data System (ADS)

Bellis, Matthew; CMS Collaboration

2016-03-01

The CERN Open Data Portal provides access to data from the LHC experiments to anyone with the time and inclination to learn the analysis procedures. The CMS experiment has made a significant amount of data availible in basically the same format the collaboration itself uses, along with software tools and a virtual enviroment in which to run those tools. These same data have also been mined for educational exercises that range from very simple .csv files that can be analyzed in a spreadsheet to more sophisticated formats that use ROOT, a dominant software package in experimental particle physics but not used as much in the general computing community. This talk will present the Particle Physics Playground website (http://particle-physics-playground.github.io/), a project that uses data from the CMS experiment, as well as the older CLEO experiment, in tutorials and exercises aimed at high school and undergraduate students and other science enthusiasts. The data are stored as text files and the users are provided with starter Python/Jupyter notebook programs and accessor functions which can be modified to perform fairly high-level analyses. The status of the project, success stories, and future plans for the website will be presented. This work was supported in part by NSF Grant PHY-1307562.

Impact of chronic maternal stress during early gestation on maternal-fetal stress transfer and fetal stress sensitivity in sheep.

PubMed

Dreiling, Michelle; Schiffner, Rene; Bischoff, Sabine; Rupprecht, Sven; Kroegel, Nasim; Schubert, Harald; Witte, Otto W; Schwab, Matthias; Rakers, Florian

2018-01-01

Acute stress-induced reduction of uterine blood flow (UBF) is an indirect mechanism of maternal-fetal stress transfer during late gestation. Effects of chronic psychosocial maternal stress (CMS) during early gestation, as may be experienced by many working women, on this stress signaling mechanism are unclear. We hypothesized that CMS in sheep during early gestation augments later acute stress-induced decreases of UBF, and aggravates the fetal hormonal, cardiovascular, and metabolic stress responses during later development. Six pregnant ewes underwent repeated isolation stress (CMS) between 30 and 100 days of gestation (dGA, term: 150 dGA) and seven pregnant ewes served as controls. At 110 dGA, ewes were chronically instrumented and underwent acute isolation stress. The acute stress decreased UBF by 19% in both the CMS and control groups (p < .05), but this was prolonged in CMS versus control ewes (74 vs. 30 min, p < .05). CMS increased fetal circulating baseline and stress-induced cortisol and norepinephrine concentrations indicating a hyperactive hypothalamus-pituitary-adrenal (HPA)-axis and sympathetic-adrenal-medullary system. Increased fetal norepinephrine is endogenous as maternal catecholamines do not cross the placenta. Cortisol in the control but not in the CMS fetuses was correlated with maternal cortisol blood concentrations; these findings indicate: (1) no increased maternal-fetal cortisol transfer with CMS, (2) cortisol production in CMS fetuses when the HPA-axis is normally inactive, due to early maturation of the fetal HPA-axis. CMS fetuses were better oxygenated, without shift towards acidosis compared to the controls, potentially reflecting adaptation to repeated stress. Hence, CMS enhances maternal-fetal stress transfer by prolonged reduction in UBF and increased fetal HPA responsiveness.

Blockade of AT1 type receptors for angiotensin II prevents cardiac microvascular fibrosis induced by chronic stress in Sprague-Dawley rats.

PubMed

Firoozmand, Lília Taddeo; Sanches, Andrea; Damaceno-Rodrigues, Nilsa Regina; Perez, Juliana Dinéia; Aragão, Danielle Sanches; Rosa, Rodolfo Mattar; Marcondes, Fernanda Klein; Casarini, Dulce Elena; Caldini, Elia Garcia; Cunha, Tatiana Sousa

2018-04-20

To test the effects of chronic-stress on the cardiovascular system, the model of chronic mild unpredictable stress (CMS) has been widely used. The CMS protocol consists of the random, intermittent, and unpredictable exposure of laboratory animals to a variety of stressors, during 3 consecutive weeks. In this study, we tested the hypothesis that exposure to the CMS protocol leads to left ventricle microcirculatory remodeling that can be attenuated by angiotensin II receptor blockade. Male Sprague-Dawley rats were randomly assigned into four groups: Control, Stress, Control + losartan, and Stress + losartan (N = 6, each group, losartan: 20 mg/kg/day). The rats were euthanized 15 days after CMS exposure, and blood samples and left ventricle were collected. Rats submitted to CMS presented increased glycemia, corticosterone, noradrenaline and adrenaline concentration, and losartan reduced the concentration of the circulating amines. Cardiac angiotensin II, measured by high-performance liquid chromatography (HPLC), was significantly increased in the CMS group, and losartan treatment reduced it, while angiotensin 1-7 was significantly higher in the CMS losartan-treated group as compared with CMS. Histological analysis, verified by transmission electron microscopy, showed that rats exposed to CMS presented increased perivascular collagen and losartan effectively prevented the development of this process. Hence, CMS induced a state of microvascular disease, with increased perivascular collagen deposition, that may be the trigger for further development of cardiovascular disease. In this case, CMS fibrosis is associated with increased production of catecholamines and with a disruption of renin-angiotensin system balance, which can be prevented by angiotensin II receptor blockade.

Stability of colistin methanesulfonate in pharmaceutical products and solutions for administration to patients.

PubMed

Wallace, Stephanie J; Li, Jian; Rayner, Craig R; Coulthard, Kingsley; Nation, Roger L

2008-09-01

Colistin methanesulfonate (CMS) has the potential to hydrolyze in aqueous solution to liberate colistin, its microbiologically active and more toxic parent compound. While conversion of CMS to colistin in vivo is important for bactericidal activity, liberation of colistin during storage and/or use of pharmaceutical formulations may potentiate the toxicity of CMS. To date, there has been no information available regarding the stability of CMS in pharmaceutical preparations. Two commercial CMS formulations were investigated for stability with respect to colistin content, which was measured by a specific high-performance liquid chromatography method. Coly-Mycin M Parenteral (colistimethate lyophilized powder) was stable (<0.1% of CMS present as colistin) for at least 20 weeks at 4 degrees C and 25 degrees C at 60% relative humidity. When Coly-Mycin M was reconstituted with 2 ml of water to a CMS concentration of 200 mg/ml for injection, Coly-Mycin M was stable (<0.1% colistin formed) for at least 7 days at both 4 degrees C and 25 degrees C. When further diluted to 4 mg/ml in a glucose (5%) or saline (0.9%) infusion solution as directed, CMS hydrolyzed faster at 25 degrees C (<4% colistin formed after 48 h) than at 4 degrees C (0.3% colistin formed). The second formulation, CMS Solution for Inhalation (77.5 mg/ml), was stable at 4 degrees C and 25 degrees C for at least 12 months, as determined based on colistin content (<0.1%). This study demonstrated the concentration- and temperature-dependent hydrolysis of CMS. The information provided by this study has important implications for the formulation and clinical use of CMS products.

Evaluation of Flagging Criteria of United States Kidney Transplant Center Performance: How to Best Define Outliers?

PubMed

Schold, Jesse D; Miller, Charles M; Henry, Mitchell L; Buccini, Laura D; Flechner, Stuart M; Goldfarb, David A; Poggio, Emilio D; Andreoni, Kenneth A

2017-06-01

Scientific Registry of Transplant Recipients report cards of US organ transplant center performance are publicly available and used for quality oversight. Low center performance (LP) evaluations are associated with changes in practice including reduced transplant rates and increased waitlist removals. In 2014, Scientific Registry of Transplant Recipients implemented new Bayesian methodology to evaluate performance which was not adopted by Center for Medicare and Medicaid Services (CMS). In May 2016, CMS altered their performance criteria, reducing the likelihood of LP evaluations. Our aims were to evaluate incidence, survival rates, and volume of LP centers with Bayesian, historical (old-CMS) and new-CMS criteria using 6 consecutive program-specific reports (PSR), January 2013 to July 2015 among adult kidney transplant centers. Bayesian, old-CMS and new-CMS criteria identified 13.4%, 8.3%, and 6.1% LP PSRs, respectively. Over the 3-year period, 31.9% (Bayesian), 23.4% (old-CMS), and 19.8% (new-CMS) of centers had 1 or more LP evaluation. For small centers (<83 transplants/PSR), there were 4-fold additional LP evaluations (52 vs 13 PSRs) for 1-year mortality with Bayesian versus new-CMS criteria. For large centers (>183 transplants/PSR), there were 3-fold additional LP evaluations for 1-year mortality with Bayesian versus new-CMS criteria with median differences in observed and expected patient survival of -1.6% and -2.2%, respectively. A significant proportion of kidney transplant centers are identified as low performing with relatively small survival differences compared with expected. Bayesian criteria have significantly higher flagging rates and new-CMS criteria modestly reduce flagging. Critical appraisal of performance criteria is needed to assess whether quality oversight is meeting intended goals and whether further modifications could reduce risk aversion, more efficiently allocate resources, and increase transplant opportunities.

Substantial Targeting Advantage Achieved by Pulmonary Administration of Colistin Methanesulfonate in a Large-Animal Model

PubMed Central

Nguyen, Tri-Hung; Lieu, Linh Thuy; Nguyen, Gary; Bischof, Robert J.; Meeusen, Els N.; Li, Jian; Nation, Roger L.

2016-01-01

ABSTRACT Colistin, administered as its inactive prodrug colistin methanesulfonate (CMS), is often used in multidrug-resistant Gram-negative pulmonary infections. The CMS and colistin pharmacokinetics in plasma and epithelial lining fluid (ELF) following intravenous and pulmonary dosing have not been evaluated in a large-animal model with pulmonary architecture similar to that of humans. Six merino sheep (34 to 43 kg body weight) received an intravenous or pulmonary dose of 4 to 8 mg/kg CMS (sodium) or 2 to 3 mg/kg colistin (sulfate) in a 4-way crossover study. Pulmonary dosing was achieved via jet nebulization through an endotracheal tube cuff. CMS and colistin were quantified in plasma and bronchoalveolar lavage fluid (BALF) samples by high-performance liquid chromatography (HPLC). ELF concentrations were calculated via the urea method. CMS and colistin were comodeled in S-ADAPT. Following intravenous CMS or colistin administration, no concentrations were quantifiable in BALF samples. Elimination clearance was 1.97 liters/h (4% interindividual variability) for CMS (other than conversion to colistin) and 1.08 liters/h (25%) for colistin. On average, 18% of a CMS dose was converted to colistin. Following pulmonary delivery, colistin was not quantifiable in plasma and CMS was detected in only one sheep. Average ELF concentrations (standard deviations [SD]) of formed colistin were 400 (243), 384 (187), and 184 (190) mg/liter at 1, 4, and 24 h after pulmonary CMS administration. The population pharmacokinetic model described well CMS and colistin in plasma and ELF following intravenous and pulmonary administration. Pulmonary dosing provided high ELF and low plasma colistin concentrations, representing a substantial targeting advantage over intravenous administration. Predictions from the pharmacokinetic model indicate that sheep are an advantageous model for translational research. PMID:27821445

Underreporting of nursing home utilization on the CMS-2728 in older incident dialysis patients and implications for assessing mortality risk.

PubMed

Bowling, C Barrett; Zhang, Rebecca; Franch, Harold; Huang, Yijian; Mirk, Anna; McClellan, William M; Johnson, Theodore M; Kutner, Nancy G

2015-03-21

The usage of nursing home (NH) services is a marker of frailty among older adults. Although the Centers for Medicare & Medicaid Services (CMS) revised the Medical Evidence Report Form CMS-2728 in 2005 to include data collection on NH institutionalization, the validity of this item has not been reported. There were 27,913 patients ≥ 75 years of age with incident end-stage renal disease (ESRD) in 2006, which constituted our analysis cohort. We determined the accuracy of the CMS-2728 using a matched cohort that included the CMS Minimum Data Set (MDS) 2.0, often employed as a "gold standard" metric for identifying patients receiving NH care. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the CMS-2728 NH item. Next, we compared characteristics and mortality risk by CMS-2728 and MDS NH status agreement. The sensitivity, specificity, PPV and NPV of the CMS-2728 for NH status were 33%, 97%, 80% and 79%, respectively. Compared to those without the MDS or CMS-2728 NH indicator (No MDS/No 2728), multivariable adjusted hazard ratios (95% confidence interval) for mortality associated with NH status were 1.55 (1.46 - 1.64) for MDS/2728, 1.48 (1.42 - 1.54) for MDS/No 2728, and 1.38 (1.25 - 1.52) for No MDS/2728. NH utilization was more strongly associated with mortality than other CMS-2728 items in the model. The CMS-2728 underestimated NH utilization among older adults with incident ESRD. The potential for misclassification may have important ramifications for assessing prognosis, developing advanced care plans and providing coordinated care.

Characterization and classification of one new cytoplasmic male sterility (CMS) line based on morphological, cytological and molecular markers in non-heading Chinese cabbage (Brassica rapa L.).

PubMed

Heng, Shuangping; Shi, Dianyi; Hu, Zhenhua; Huang, Tao; Li, Jinping; Liu, Liyan; Xia, Chunxiu; Yuan, Zhenzhen; Xu, Yuejin; Fu, Tingdong; Wan, Zhengjie

2015-09-01

A new non-heading Chinese cabbage CMS line M119A was characterized and specific molecular markers were developed to classify different CMS types. One new non-heading Chinese cabbage (Brassica rapa L.) cytoplasmic male sterile (CMS) line M119A was obtained by interspecific crosses between the recently discovered hau CMS line of Brassica juncea and B. rapa. Furthermore, the line was characterized and compared with other five isonuclear-alloplasmic CMS lines. The M119A line produced six stamens without pollen and only two stamen fused together in fewer flowers. Tissue section indicated that anther abortion in M119A may have occurred during differentiation of the archesporial cells without pollen sac. All the six CMS lines were grouped into three types based on the presence of three PCR fragments of 825, 465 and 772 bp amplified with different mitochondrial genes specific primers. The 825-bp fragment was amplified both in 09-10A and H201A using the specific primer pair P-orf224-atp6, and showed 100 % identity with the mitochondrial gene of pol CMS. The 465-bp fragment was amplified in 30A and 105A using the primer pair P-orf138 and shared 100 % identity with the mitochondrial gene of ogu CMS. The 772-bp fragment was amplified in M119A and H203A using the primer pair P-orf288 and showed 100 % identity with the mitochondrial gene of hau CMS. Therefore, these markers could efficiently distinguish different types of isonuclear-alloplasmic CMS lines of non-heading Chinese cabbage, which were useful for improving the efficiency of cross-breeding and heterosis utilization in cruciferous vegetables.

Stability of Colistin Methanesulfonate in Pharmaceutical Products and Solutions for Administration to Patients▿

PubMed Central

Wallace, Stephanie J.; Li, Jian; Rayner, Craig. R.; Coulthard, Kingsley; Nation, Roger L.

2008-01-01

Colistin methanesulfonate (CMS) has the potential to hydrolyze in aqueous solution to liberate colistin, its microbiologically active and more toxic parent compound. While conversion of CMS to colistin in vivo is important for bactericidal activity, liberation of colistin during storage and/or use of pharmaceutical formulations may potentiate the toxicity of CMS. To date, there has been no information available regarding the stability of CMS in pharmaceutical preparations. Two commercial CMS formulations were investigated for stability with respect to colistin content, which was measured by a specific high-performance liquid chromatography method. Coly-Mycin M Parenteral (colistimethate lyophilized powder) was stable (<0.1% of CMS present as colistin) for at least 20 weeks at 4°C and 25°C at 60% relative humidity. When Coly-Mycin M was reconstituted with 2 ml of water to a CMS concentration of 200 mg/ml for injection, Coly-Mycin M was stable (<0.1% colistin formed) for at least 7 days at both 4°C and 25°C. When further diluted to 4 mg/ml in a glucose (5%) or saline (0.9%) infusion solution as directed, CMS hydrolyzed faster at 25°C (<4% colistin formed after 48 h) than at 4°C (0.3% colistin formed). The second formulation, CMS Solution for Inhalation (77.5 mg/ml), was stable at 4°C and 25°C for at least 12 months, as determined based on colistin content (<0.1%). This study demonstrated the concentration- and temperature-dependent hydrolysis of CMS. The information provided by this study has important implications for the formulation and clinical use of CMS products. PMID:18606838

Factors affecting pharmacists’ recommendation of complementary medicines – a qualitative pilot study of Australian pharmacists

PubMed Central

2012-01-01

Background Complementary medicines (CMs) are widely used by the Australian public, and pharmacies are major suppliers of these medicines. The integration of CMs into pharmacy practice is well documented, but the behaviours of pharmacists in recommending CMs to customers are less well studied. This study reports on factors that influence whether or not pharmacists in Australia recommend CMs to their customers. Methods Data were collected from semi-structured interviews with twelve practicing pharmacists based in Brisbane, Australia. The qualitative data were analysed by thematic analysis. Results The primary driver of the recommendation of CMs was a desire to provide a health benefit to the customer. Other important drivers were an awareness of evidence of efficacy, customer feedback and pharmacy protocols to recommend a CM alongside a particular pharmaceutical medication. The primary barrier to the recommendation of CMs was safety concerns around patients on multiple medications or with complex health issues. Also, a lack of knowledge of CMs, a perceived lack of evidence or a lack of time to counsel patients were identified as barriers. There was a desire to see a greater integration of CM into formal pharmacy education. Additionally, the provision of good quality educational materials was seen as important to allow pharmacists to assess levels of evidence for CMs and educate them on their safe and appropriate use. Conclusions Pharmacists who frequently recommend CMs identify many potential benefits for patients and see it as an important part of providing a ‘healthcare solution’. To encourage the informed use of CMs in pharmacy there is a need for the development of accessible, quality resources on CMs. In addition, incorporation of CM education into pharmacy curricula would better prepare graduate pharmacists for community practice. Ultimately, such moves would contribute to the safe and effective use of CMs to the benefit of consumers. PMID:23051066

Burden of disease resulting from chronic mountain sickness among young Chinese male immigrants in Tibet

PubMed Central

2012-01-01

Background In young Chinese men of the highland immigrant population, chronic mountain sickness (CMS) is a major public health problem. The aim of this study was to measure the disease burden of CMS in this population. Methods We used disability-adjusted life years (DALYs) to estimate the disease burden of CMS. Disability weights were derived using the person trade-off methodology. CMS diagnoses, symptom severity, and individual characteristics were obtained from surveys collected in Tibet in 2009 and 2010. The DALYs of individual patients and the DALYs/1,000 were calculated. Results Disability weights were obtained for 21 CMS health stages. The results of the analyses of the two surveys were consistent with each other. At different altitudes, the CMS rates ranged from 2.1-37.4%; the individual DALYs of patients ranged from 0.13-0.33, and the DALYs/1,000 ranged from 3.60-52.78. The age, highland service years, blood pressure, heart rate, smoking rate, and proportion of the sample working in engineering or construction were significantly higher in the CMS group than in the non-CMS group (p < 0.05). These variables were also positively associated with the individual DALYs (p < 0.05). Among the symptoms, headaches caused the largest proportion of DALYs. Conclusion The results show that CMS imposes a considerable burden on Chinese immigrants to Tibet. Immigrants with characteristics such as a higher residential altitude, more advanced age, longer highland service years, being a smoker, and working in engineering or construction were more likely to develop CMS and to increase the disease burden. Higher blood pressure and heart rate as a result of CMS were also positively associated with the disease burden. The authorities should pay attention to the highland disease burden and support the development and application of DALYs studies of CMS and other highland diseases. PMID:22672510

Experimental particle physics research at Texas Tech University

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

Akchurin, Nural; Lee, Sung-Won; Volobouev, Igor

The high energy physics group at Texas Tech University (TTU) concentrates its research efforts on the Compact Muon Solenoid (CMS) experiment at the Large Hadron Collider (LHC) and on generic detector R&D for future applications. Our research programs have been continuously supported by the US Department of Energy for over two decades, and this final report summarizes our achievements during the last grant period from May 1, 2012 to March 31, 2016. After having completed the Run 1 data analyses from the CMS detector, including the discovery of the Higgs boson in July 2012, we concentrated on commissioning the CMSmore » hadron calorimeter (HCAL) for Run 2, performing analyses of Run 2 data, and making initial studies and plans for the second phase of upgrades in CMS. Our research has primarily focused on searches for Beyond Standard Model (BSM) physics via dijets, monophotons, and monojets. We also made significant contributions to the analyses of the semileptonic Higgs decays and Standard Model (SM) measurements in Run 1. Our work on the operations of the CMS detector, especially the performance monitoring of the HCAL in Run 1, was indispensable to the experiment. Our team members, holding leadership positions in HCAL, have played key roles in the R&D, construction, and commissioning of these detectors in the last decade. We also maintained an active program in jet studies that builds on our expertise in calorimetry and algorithm development. In Run 2, we extended some of our analyses at 8 TeV to 13 TeV, and we also started to investigate new territory, e.g., dark matter searches with unexplored signatures. The objective of dual-readout calorimetry R&D was intended to explore (and, if possible, eliminate) the obstacles that prevent calorimetric detection of hadrons and jets with a comparable level of precision as we have grown accustomed to for electrons and photons. The initial prototype detector was successfully tested at the SPS/CERN in 2003-2004 and evolved over the last decade. In 2012-2015, several other prototypes were built to further reduce leakage fluctuations, improve Cherenkov light yield, increase fiber attenuation length, and other related phenomena. During this grant period, we graduated two students with Ph.D. degrees, and five undergraduate students from our labs went on to prestigious graduate programs in the US and Europe. Also, the TTU HEP team has participated in the QuarkNet program every year since 2001. We are dedicated to working with area teachers and students at all levels and to training the next generation of scientists. Over 20 high school teachers have participated in our program since its inception.« less

CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Excellent Passivation of p-Type Si Surface by Sol-Gel Al2O3 Films

NASA Astrophysics Data System (ADS)

Xiao, Hai-Qing; Zhou, Chun-Lan; Cao, Xiao-Ning; Wang, Wen-Jing; Zhao, Lei; Li, Hai-Ling; Diao, Hong-Wei

2009-08-01

Al2O3 films with a thickness of about 100 nm synthesized by spin coating and thermally treated are applied for field-induced surface passivation of p-type crystalline silicon. The level of surface passivation is determined by techniques based on photoconductance. An effective surface recombination velocity below 100 cm/s is obtained on 10Ω ·cm p-type c-Si wafers (Cz Si). A high density of negative fixed charges in the order of 1012 cm-2 is detected in the Al2O3 films and its impact on the level of surface passivation is demonstrated experimentally. Furthermore, a comparison between the surface passivation achieved for thermal SiO2 and plasma enhanced chemical vapor deposition SiNx:H films on the same c-Si is presented. The high negative fixed charge density explains the excellent passivation of p-type c-Si by Al2O3.

Phenomenology of 2HDM with vectorlike quarks

NASA Astrophysics Data System (ADS)

Arhrib, A.; Benbrik, R.; King, S. J. D.; Manaut, B.; Moretti, S.; Un, C. S.

2018-05-01

In this paper, we examine the consistency of the Large Hadron Collider (LHC) data collected during Runs 1 and 2 by the ATLAS and CMS experiments with the predictions of a 2-Higgs doublet model embedding vectorlike quarks (VLQs) for p p →H , A production and H , A →γ γ decay mechanisms, respectively, of (nearly) degenerate C P -even (H ) and C P -odd (A ) Higgs bosons. We show that a scenario containing one single VLQ with electromagnetic charge 2 /3 can explain the above ATLAS and CMS data for masses in the region 350 GeV ≤mVLQ≤1.5 TeV or so, depending on tan β , and for several values of the mixing angle between the top quark (t ) and its VLQ counterpart (T ). We then perform a global fit onto the model by including all relevant experimental as well as theoretical constraints. The surviving samples of our analysis are discussed within 2 σ of the LHC measurements. Additionally, we also comment on the recent anomalous result reported by CMS using Run 2 data on the associated Standard Model Higgs boson production with top quark pairs p p →t t ¯ h with an observed significance of 3.3 σ . Other than these specific examples, we also present a phenomenological analysis of the main features of the model, including the most promising T decay channels.

A review on III-V core-multishell nanowires: growth, properties, and applications

NASA Astrophysics Data System (ADS)

Royo, Miquel; De Luca, Marta; Rurali, Riccardo; Zardo, Ilaria

2017-04-01

This review focuses on the emerging field of core-multishell (CMS) semiconductor nanowires (NWs). In these kinds of wires, a NW grown vertically on a substrate acts as a template for the coaxial growth of two or more layers wrapped around it. Thanks to the peculiar geometry, the strain is partially released along the radial direction, thus allowing the creation of fascinating heterostructures, even based on lattice mismatched materials that would hardly grow in a planar geometry. Enabling the unique bridging of the 1D nature of NWs with the exciting properties of 2D heterostructures, these novel systems are becoming attractive for material science, as well as fundamental and applied physics. We will focus on NWs made of III-V and III-V-based alloys as they represent a model system in which present growth techniques have reached a high degree of control on the material structural properties, and many physical properties have been assessed, from both the theoretical and experimental points of view. In particular, we provide an overview on the growth methods and structural properties of CMS NWs, on the modulation doping mechanisms enabled by these heterostructures, on the effects of a magnetic field, and on the phononic and optical properties typical of CMS NWs. Moreover, we review the main technological applications based on these systems, such as optoelectronic and photovoltaic devices.

Beam test evaluation of electromagnetic calorimeter modules made from proton-damaged PbWO4 crystals

NASA Astrophysics Data System (ADS)

Adams, T.; Adzic, P.; Ahuja, S.; Anderson, D.; Andrews, M. B.; Antropov, I.; Antunovic, Z.; Arcidiacono, R.; Arenton, M. W.; Argirò, S.; Askew, A.; Attikis, A.; Auffray, E.; Baccaro, S.; Baffioni, S.; Bailleux, D.; Baillon, P.; Barney, D.; Barone, L.; Bartoloni, A.; Bartosik, N.; Becheva, E.; Bein, S.; Silva, C. Beirāo Da Cruz E.; Bell, K. W.; Benaglia, A.; Bendavid, J.; Berry, D.; Besancon, M.; Betev, B.; Bialas, W.; Bianchini, L.; Biino, C.; Bitioukov, S.; Bornheim, A.; Brianza, L.; Brinkerhoff, A.; Brown, R. M.; Brummitt, A.; Busson, P.; Candelise, V.; Carrillo Montoya, C. A.; Cartiglia, N.; Cavallari, F.; Chang, Y. W.; Chen, K. F.; Chevenier, G.; Chipaux, R.; Clement, E.; Cockerill, D. J. A.; Corpe, L.; Couderc, F.; Courbon, B.; Cox, B.; Cucciati, G.; Cussans, D.; D'imperio, G.; Da Silva Di Calafiori, D. R.; Dafinei, I.; Daguin, J.; Daskalakis, G.; Tinoco Mendes, A. D.; De Guio, F.; Degano, A.; Dejardin, M.; Del Re, D.; Della Ricca, G.; Denegri, D.; Depasse, P.; Dev, N.; Deyrail, D.; Di Marco, E.; Diamond, B.; Diemoz, M.; Dissertori, G.; Dittmar, M.; Djambazov, L.; Doan, T. H.; Dobrzynski, L.; Dolgopolov, A.; Donegà, M.; Dordevic, M.; Dröge, M.; Durkin, T.; Dutta, D.; El Mamouni, H.; Elliott-Peisert, A.; Elmalis, E.; Fabbro, B.; Fasanella, G.; Faure, J.; Fay, J.; Fedorov, A.; Ferri, F.; Francis, B.; Frank, N.; Franzoni, G.; Funk, W.; Ganjour, S.; Gascon, S.; Gastal, M.; Geerebaert, Y.; Gelli, S.; Gerosa, R.; Ghezzi, A.; Giakoumopoulou, V. A.; Givernaud, A.; Gninenko, S.; Godinovic, N.; Goeckner-Wald, N.; Golubev, N.; Govoni, P.; Gras, P.; Guilloux, F.; Haller, C.; Hamel de Monchenault, G.; Hansen, M.; Hansen, P.; Hardenbrook, J.; Heath, H. F.; Hill, J.; Hirosky, R.; Hobson, P. R.; Holme, O.; Honma, A.; Hou, W.-S.; Hsiung, Y.; Iiyama, Y.; Ille, B.; Ingram, Q.; Jain, S.; Jarry, P.; Jessop, C.; Jovanovic, D.; Kachanov, V.; Kalafut, S.; Kao, K. Y.; Kellams, N.; Kesisoglou, S.; Khatiwada, A.; Konoplyannikov, A.; Konstantinov, D.; Korzhik, M.; Kovac, M.; Kubota, Y.; Kucher, I.; Kumar, A.; Kumar, A.; Kuo, C.; Kyberd, P.; Kyriakis, A.; Latyshev, G.; Lecoq, P.; Ledovskoy, A.; Lei, Y. J.; Lelas, D.; Lethuillier, M.; Li, H.; Lin, W.; Liu, Y. F.; Locci, E.; Longo, E.; Loukas, D.; Lu, R.-S.; Lucchini, M. T.; Lustermann, W.; Mackay, C. K.; Magniette, F.; Malcles, J.; Malhotra, S.; Mandjavidze, I.; Maravin, Y.; Margaroli, F.; Marinelli, N.; Marini, A. C.; Martelli, A.; Marzocchi, B.; Massironi, A.; Matveev, V.; Mechinsky, V.; Meng, F.; Meridiani, P.; Micheli, F.; Milosevic, J.; Mousa, J.; Musella, P.; Nessi-Tedaldi, F.; Neu, C.; Newman, H.; Nicolaou, C.; Nourbakhsh, S.; Obertino, M. M.; Organtini, G.; Orimoto, T.; Paganini, P.; Paganis, E.; Paganoni, M.; Pandolfi, F.; Panov, V.; Paramatti, R.; Parracho, P.; Pastrone, N.; Paulini, M.; Pauss, F.; Pauwels, K.; Pellegrino, F.; Pena, C.; Perniè, L.; Peruzzi, M.; Petrakou, E.; Petyt, D.; Pigazzini, S.; Piroué, P.; Planer, M.; Plestina, R.; Polic, D.; Prosper, H.; Ptochos, F.; Puljak, I.; Quittnat, M.; Ragazzi, S.; Rahatlou, S.; Rander, J.; Ranjan, K.; Rasteiro Da Silva, J.; Razis, P. A.; Romanteau, T.; Rosowsky, A.; Rovelli, C.; Rusack, R.; Salerno, R.; Santanastasio, F.; Santra, A.; Schönenberger, M.; Seez, C.; Sharma, V.; Shepherd-Themistocleous, C.; Shiu, J. G.; Shivpuri, R. K.; Singovsky, A.; Sinthuprasith, T.; Sirois, Y.; Smiljkovic, N.; Soffi, L.; Sun, M.; Symonds, P.; Tabarelli de Fatis, T.; Tambe, N.; Tarasov, I.; Taroni, S.; Teixeira De Lima, R.; Thea, A.; Theofilatos, K.; Thiant, F.; Titov, M.; Torbet, M.; Trapani, P. P.; Tropea, P.; Tsai, J. f.; Tsirou, A.; Turkewitz, J.; Tyurin, N.; Tzeng, Y. M.; Uzunian, A.; Valls, N.; Varela, J.; Veeraraghavan, V.; Verdini, P. G.; Vichoudis, P.; Vlassov, E.; Wang, J.; Wang, T.; Weinberg, M.; Wolfe, E.; Wood, J.; Zabi, A.; Zahid, S.; Zelepoukine, S.; Zghiche, A.; Zhang, L.; Zhu, K.; Zhu, R.; Zuyeuski, R.

2016-04-01

The performance of electromagnetic calorimeter modules made of proton-irradiated PbWO4 crystals has been studied in beam tests. The modules, similar to those used in the Endcaps of the CMS electromagnetic calorimeter (ECAL), were formed from 5×5 matrices of PbWO4 crystals, which had previously been exposed to 24 GeV protons up to integrated fluences between 2.1× 1013 and 1.3× 1014 cm-2. These correspond to the predicted charged-hadron fluences in the ECAL Endcaps at pseudorapidity η = 2.6 after about 500 fb-1 and 3000 fb-1 respectively, corresponding to the end of the LHC and High Luminosity LHC operation periods. The irradiated crystals have a lower light transmission for wavelengths corresponding to the scintillation light, and a correspondingly reduced light output. A comparison with four crystals irradiated in situ in CMS showed no significant rate dependence of hadron-induced damage. A degradation of the energy resolution and a non-linear response to electron showers are observed in damaged crystals. Direct measurements of the light output from the crystals show the amplitude decreasing and pulse becoming faster as the fluence increases. The latter is interpreted, through comparison with simulation, as a side-effect of the degradation in light transmission. The experimental results obtained can be used to estimate the long term performance of the CMS ECAL.

42 CFR 423.509 - Termination of contract by CMS.

Code of Federal Regulations, 2010 CFR

2010-10-01

...: (1) Termination of contract by CMS. (i) CMS notifies the Part D plan in writing 90 days before the... difficulties so severe that its ability to make necessary health services available is impaired to the point of... writing that its contract will be terminated on a date specified by CMS. If a termination in is effective...

42 CFR 423.509 - Termination of contract by CMS.

Code of Federal Regulations, 2011 CFR

2011-10-01

...: (1) Termination of contract by CMS. (i) CMS notifies the Part D plan in writing 90 days before the... difficulties so severe that its ability to make necessary health services available is impaired to the point of... writing that its contract will be terminated on a date specified by CMS. If a termination in is effective...

42 CFR 423.758 - Collection of civil money penalties imposed by CMS.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 3 2014-10-01 2014-10-01 false Collection of civil money penalties imposed by CMS... BENEFIT Intermediate Sanctions § 423.758 Collection of civil money penalties imposed by CMS. (a) When a Part D plan sponsor does not request a hearing CMS initiates collection of the civil money penalty...

42 CFR 422.758 - Collection of civil money penalties imposed by CMS.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 3 2014-10-01 2014-10-01 false Collection of civil money penalties imposed by CMS... Sanctions § 422.758 Collection of civil money penalties imposed by CMS. (a) When an MA organization does not request a hearing, CMS initiates collection of the civil money penalty following the expiration of the...

42 CFR 422.758 - Collection of civil money penalties imposed by CMS.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 3 2011-10-01 2011-10-01 false Collection of civil money penalties imposed by CMS... § 422.758 Collection of civil money penalties imposed by CMS. (a) When an MA organization does not request a hearing, CMS initiates collection of the civil money penalty following the expiration of the...

42 CFR 422.758 - Collection of civil money penalties imposed by CMS.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 3 2013-10-01 2013-10-01 false Collection of civil money penalties imposed by CMS... Sanctions § 422.758 Collection of civil money penalties imposed by CMS. (a) When an MA organization does not request a hearing, CMS initiates collection of the civil money penalty following the expiration of the...

45 CFR 150.303 - Basis for initiating an investigation of a potential violation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS... may be failing to meet an applicable HIPAA requirement, may warrant an investigation. CMS may consider... acting on that individual's behalf, may file a complaint with CMS if he or she believes that a right to...

42 CFR 433.320 - Procedures for refunds to CMS.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Procedures for refunds to CMS. 433.320 Section 433... Overpayments to Providers § 433.320 Procedures for refunds to CMS. (a) Basic requirements. (1) The agency must refund the Federal share of overpayments that are subject to recovery to CMS through a credit on its...

42 CFR 422.758 - Collection of civil money penalties imposed by CMS.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Collection of civil money penalties imposed by CMS... § 422.758 Collection of civil money penalties imposed by CMS. (a) When an MA organization does not request a hearing, CMS initiates collection of the civil money penalty following the expiration of the...

42 CFR 447.256 - Procedures for CMS action on assurances and State plan amendments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Procedures for CMS action on assurances and State... for Inpatient Hospital and Long-Term Care Facility Services Payment Rates § 447.256 Procedures for CMS action on assurances and State plan amendments. (a) Criteria for approval. (1) CMS approval action on...

42 CFR 438.730 - Sanction by CMS: Special rules for MCOs

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Sanction by CMS: Special rules for MCOs 438.730... SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS MANAGED CARE Sanctions § 438.730 Sanction by CMS: Special rules for MCOs (a) Basis for sanction. (1) A State agency may recommend that CMS impose the denial of...

42 CFR 411.380 - When CMS issues a formal advisory opinion.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false When CMS issues a formal advisory opinion. 411.380... Relationships Between Physicians and Entities Furnishing Designated Health Services § 411.380 When CMS issues a formal advisory opinion. (a) CMS considers an advisory opinion to be issued once it has received payment...

42 CFR 426.515 - CMS' role in making the NCD record available.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false CMS' role in making the NCD record available. 426.515 Section 426.515 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND... COVERAGE DETERMINATIONS Review of an NCD § 426.515 CMS' role in making the NCD record available. CMS will...

42 CFR 423.758 - Collection of civil money penalties imposed by CMS.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Collection of civil money penalties imposed by CMS... Intermediate Sanctions § 423.758 Collection of civil money penalties imposed by CMS. (a) When a Part D plan sponsor does not request a hearing CMS initiates collection of the civil money penalty following the...

40 CFR Appendix A to Subpart Ll of... - Applicability of General Provisions

Code of Federal Regulations, 2010 CFR

2010-07-01

... not require CMS or CMS performance evaluation. 63.8(e) Performance evaluation for CMS No 63.9(b)(1)-(5... evaluations No Subpart LL does not require performance evaluation for CMS. 63.11(a)-(b) Control device... Appendix A to Subpart LL of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

Flexible omnidirectional carbon dioxide laser as an effective tool for resection of brainstem, supratentorial, and intramedullary cavernous malformations.

PubMed

Choudhri, Omar; Karamchandani, Jason; Gooderham, Peter; Steinberg, Gary K

2014-03-01

Lasers have a long history in neurosurgery, yet bulky designs and difficult ergonomics limit their use. With its ease of manipulation and multiple applications, the OmniGuide CO2 laser has reintroduced laser technology to the microsurgical resection of brain and spine lesions. This laser, delivered through a hollow-core fiber lined with a unidirectional mirror, minimizes energy loss and allows precise targeting. To analyze resections performed by the senior author from April 2009 to March 2013 of 58 cavernous malformations (CMs) in the brain and spine with the use of the OmniGuide CO2 laser, to reflect on lessons learned from laser use in eloquent areas, and to share data on comparisons of laser power calibration and histopathology. Data were collected from electronic medical records, radiology reports, operative room records, OmniGuide CO2 laser case logs, and pathology records. Of 58 CMs, approximately 50% were in the brainstem (30) and the rest were in supratentorial (26) and intramedullary spinal locations (2). Fifty-seven, ranging from 5 to 45 mm, were resected, with a subtotal resection in 1. Laser power ranged from 2 to 10 W. Pathology specimens showed minimal thermal damage compared with traditionally resected specimens with bipolar coagulation. The OmniGuide CO2 laser is safe and has excellent precision for the resection of supratentorial, brainstem, and spinal intramedullary CMs. No laser-associated complications occurred, and very low energy was used to dissect malformations from their surrounding hemosiderin-stained parenchymas. The authors recommend its use for deep-seated and critically located CMs, along with traditional tools.

Downscaling Global Emissions and Its Implications Derived from Climate Model Experiments

PubMed Central

Abe, Manabu; Kinoshita, Tsuguki; Hasegawa, Tomoko; Kawase, Hiroaki; Kushida, Kazuhide; Masui, Toshihiko; Oka, Kazutaka; Shiogama, Hideo; Takahashi, Kiyoshi; Tatebe, Hiroaki; Yoshikawa, Minoru

2017-01-01

In climate change research, future scenarios of greenhouse gas and air pollutant emissions generated by integrated assessment models (IAMs) are used in climate models (CMs) and earth system models to analyze future interactions and feedback between human activities and climate. However, the spatial resolutions of IAMs and CMs differ. IAMs usually disaggregate the world into 10–30 aggregated regions, whereas CMs require a grid-based spatial resolution. Therefore, downscaling emissions data from IAMs into a finer scale is necessary to input the emissions into CMs. In this study, we examined whether differences in downscaling methods significantly affect climate variables such as temperature and precipitation. We tested two downscaling methods using the same regionally aggregated sulfur emissions scenario obtained from the Asian-Pacific Integrated Model/Computable General Equilibrium (AIM/CGE) model. The downscaled emissions were fed into the Model for Interdisciplinary Research on Climate (MIROC). One of the methods assumed a strong convergence of national emissions intensity (e.g., emissions per gross domestic product), while the other was based on inertia (i.e., the base-year remained unchanged). The emissions intensities in the downscaled spatial emissions generated from the two methods markedly differed, whereas the emissions densities (emissions per area) were similar. We investigated whether the climate change projections of temperature and precipitation would significantly differ between the two methods by applying a field significance test, and found little evidence of a significant difference between the two methods. Moreover, there was no clear evidence of a difference between the climate simulations based on these two downscaling methods. PMID:28076446

Value-based contracting innovated Medicare advantage healthcare delivery and improved survival.

PubMed

Mandal, Aloke K; Tagomori, Gene K; Felix, Randell V; Howell, Scott C

2017-02-01

In Medicare Advantage (MA) with its CMS Hierarchical Condition Categories (CMS-HCC) payment model, CMS reimburses private plans (Medicare Advantage Organizations [MAOs]) with prospective, monthly, health-based or risk-adjusted, capitated payments. The effect of this payment methodology on healthcare delivery remains debatable. How value-based contracting generates cost efficiencies and improves clinical outcomes in MA is studied. A difference in contracting arrangements between an MAO and 2 provider groups facilitated an intervention-control, preintervention-postintervention, difference-in-differences approach among statistically similar, elderly, community-dwelling MA enrollees within one metropolitan statistical area. Starting in 2009, for intervention-group MA enrollees, the MAO and a provider group agreed to full-risk capitation combined with a revenue gainshare. The gainshare was based on increases in the Risk Adjustment Factor (RAF), which modified the CMS-HCC payments. For the control group, the MAO continued to reimburse another provider group through fee-for-service. RAF, utilization, and survival were followed until December 31, 2012. The intervention group's mean RAF increased significantly (P <.001), estimating $2,519,544 per 1000 members of additional revenue. The intervention increased office-based visits (P <.001). Emergency department visits (P <.001) and inpatient hospital admissions (P = .002) decreased. This change in utilization saved $2,071,293 per 1000 enrollees. By intensifying office-based care for these MA enrollees with multiple comorbidities, a 6% survival benefit with a 32.8% lower hazard of death (P <.001) was achieved. Value-based contracting can drive utilization patterns and improve clinical outcomes among chronically ill, elderly MA members.

Comparative safety of anti-epileptic drugs during pregnancy: a systematic review and network meta-analysis of congenital malformations and prenatal outcomes.

PubMed

Veroniki, Areti Angeliki; Cogo, Elise; Rios, Patricia; Straus, Sharon E; Finkelstein, Yaron; Kealey, Ryan; Reynen, Emily; Soobiah, Charlene; Thavorn, Kednapa; Hutton, Brian; Hemmelgarn, Brenda R; Yazdi, Fatemeh; D'Souza, Jennifer; MacDonald, Heather; Tricco, Andrea C

2017-05-05

Pregnant women with epilepsy frequently experience seizures related to pregnancy complications and are often prescribed anti-epileptic drugs (AEDs) to manage their symptoms. However, less is known about the comparative safety of AED exposure in utero. We aimed to compare the risk of congenital malformations (CMs) and prenatal outcomes of AEDs in infants/children who were exposed to AEDs in utero through a systematic review and Bayesian random-effects network meta-analysis. MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to December 15, 2015. Two reviewers independently screened titles/abstracts and full-text papers for experimental and observational studies comparing mono- or poly-therapy AEDs versus control (no AED exposure) or other AEDs, then abstracted data and appraised the risk of bias. The primary outcome was incidence of major CMs, overall and by specific type (cardiac malformations, hypospadias, cleft lip and/or palate, club foot, inguinal hernia, and undescended testes). After screening 5305 titles and abstracts, 642 potentially relevant full-text articles, and 17 studies from scanning reference lists, 96 studies were eligible (n = 58,461 patients). Across all major CMs, many AEDs were associated with higher risk compared to control. For major CMs, ethosuximide (OR, 3.04; 95% CrI, 1.23-7.07), valproate (OR, 2.93; 95% CrI, 2.36-3.69), topiramate (OR, 1.90; 95% CrI, 1.17-2.97), phenobarbital (OR, 1.83; 95% CrI, 1.35-2.47), phenytoin (OR, 1.67; 95% CrI, 1.30-2.17), carbamazepine (OR, 1.37; 95% CrI, 1.10-1.71), and 11 polytherapies were significantly more harmful than control, but lamotrigine (OR, 0.96; 95% CrI, 0.72-1.25) and levetiracetam (OR, 0.72; 95% CrI, 0.43-1.16) were not. The newer generation AEDs, lamotrigine and levetiracetam, were not associated with significant increased risks of CMs compared to control, and were significantly less likely to be associated with children experiencing cardiac malformations than control. However, this does not mean that these agents are not harmful to infants/children exposed in utero. Counselling is advised concerning teratogenic risks when the prescription is written for a woman of childbearing age and before women continue with these agents when considering pregnancy, such as switching from polytherapy to monotherapy with evidence of lower risk and avoiding AEDs, such as valproate, that are consistently associated with CMs. These decisions must be balanced against the need for seizure control. PROSPERO CRD42014008925.

42 CFR 422.100 - General requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... in the service area of the MA plan; (2) At a uniform premium, with uniform benefits and level of cost... review and approval of MA benefits and associated cost sharing. CMS reviews and approves MA benefits and... 42 Public Health 3 2010-10-01 2010-10-01 false General requirements. 422.100 Section 422.100...

77 FR 29647 - Medicare Program; Solicitation for Proposals for the Medicare Graduate Nurse Education...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-18

..., Center for Medicare & Medicaid Innovation, Attention: Alexandre Laberge, Mail Stop: WB-06-05, 7500... underserved areas. On March 22, 2012, we posted a solicitation for proposals on the Innovation Center Web site... Innovation Center Web site at http://www.innovations.cms.gov/initiatives/GNE/index.html . II. Provisions of...

42 CFR 414.26 - Determining the GAF.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Geographic indices. CMS uses the following indices to establish the GAF: (1) An index that reflects one... fee schedule areas as determined under § 414.22(a) and the national average of that work effort. (2... § 414.22(b) compared to the national average of those costs. (3) An index that reflects the relative...

42 CFR 424.570 - Moratoria on newly enrolling Medicare providers and suppliers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... for fraud, waste or abuse in the Medicare program: (A) A particular provider or supplier type. (B) Any... enrollment of new Medicare providers and suppliers of a particular type or the establishment of new practice locations of a particular type in a particular geographic area. (ii) CMS will announce the temporary...

76 FR 29249 - Medicare Program; Pioneer Accountable Care Organization Model: Request for Applications

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-20

... on the Innovation Center Web site http://innovations.cms.gov/areas-of-focus/seamless-and-coordinated... Medicare and Medicaid Innovation, Centers for Medicare and Medicaid Services, Mail Stop S3-13-05, 7500... and Medicaid Innovation (Innovation Center). The Pioneer ACO Model is an Innovation Center initiative...

42 CFR 414.26 - Determining the GAF.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Geographic indices. CMS uses the following indices to establish the GAF: (1) An index that reflects one... fee schedule areas as determined under § 414.22(a) and the national average of that work effort. (2... § 414.22(b) compared to the national average of those costs. (3) An index that reflects the relative...

42 CFR 414.26 - Determining the GAF.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Geographic indices. CMS uses the following indices to establish the GAF: (1) An index that reflects one... fee schedule areas as determined under § 414.22(a) and the national average of that work effort. (2... § 414.22(b) compared to the national average of those costs. (3) An index that reflects the relative...

42 CFR 414.26 - Determining the GAF.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Geographic indices. CMS uses the following indices to establish the GAF: (1) An index that reflects one... fee schedule areas as determined under § 414.22(a) and the national average of that work effort. (2... § 414.22(b) compared to the national average of those costs. (3) An index that reflects the relative...

42 CFR 414.26 - Determining the GAF.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Geographic indices. CMS uses the following indices to establish the GAF: (1) An index that reflects one... fee schedule areas as determined under § 414.22(a) and the national average of that work effort. (2... § 414.22(b) compared to the national average of those costs. (3) An index that reflects the relative...

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

Vyas, S.N.; Patwardhan, S.R.; Vijayalakshmi, S.

Adsorption on carbon molecular sieves (CMS) prepared by coke deposition has become an interesting area of adsorption due to its microporous nature and favorable separation factor on size and shape selectivity basis for many gaseous systems. In the present work CMS was synthesized from coconut shell through three major steps, namely, carbonization, activation, and coke deposition by hydrocarbon cracking. The crushed, washed, and sieved granules of coconut shell (particle size 2--3 mm) were pretreated with sodium silicate solution and oven-dried at 150 C to create the inorganic sites necessary for coke deposition. Carbonization and activation of the dried granules weremore » carried out at 800 C, for 30 min each. The activated char thus produced was subjected to hydrocarbon cracking at 600 C for periods varying from 30 to 180 min. The product samples were characterized in terms of adsorption isotherm, kinetic adsorption curve, surface area, pore volume, pore size distribution, and characteristic energy for adsorption by using O[sub 2], N[sub 2], C[sub 2]H[sub 2], CO[sub 2], C[sub 3]H[sub 6], and CH[sub 4].« less

Low extracellular potassium prolongs repolarization and evokes early afterdepolarization in human induced pluripotent stem cell-derived cardiomyocytes.

PubMed

Kuusela, Jukka; Larsson, Kim; Shah, Disheet; Prajapati, Chandra; Aalto-Setälä, Katriina

2017-06-15

Long QT syndrome (LQTS) is characterized by a prolonged QT-interval on electrocardiogram and by increased risk of sudden death. One of the most common and potentially life-threatening electrolyte disturbances is hypokalemia, characterized by low concentrations of K + Using a multielectrode array platform and current clamp technique, we investigated the effect of low extracellular K + concentration ([K + ] Ex ) on the electrophysiological properties of hiPSC-derived cardiomyocytes (CMs) generated from a healthy control subject (WT) and from two symptomatic patients with type 1 of LQTS carrying G589D (LQT1A) or IVS7-2A>G mutation (LQT1B) in KCNQ1 The baseline prolongations of field potential durations (FPDs) and action potential durations (APDs) were longer in LQT1-CMs than in WT-CMs. Exposure to low [K + ] Ex prolonged FPDs and APDs in a concentration-dependent fashion. LQT1-CMs were found to be more sensitive to low [K + ] Ex compared to WT-CMs. At baseline, LQT1A-CMs had more prolonged APDs than LQT1B-CMs, but low [K + ] Ex caused more pronounced APD prolongation in LQT1B-CMs. Early afterdepolarizations in the action potentials were observed in a subset of LQT1A-CMs with further prolonged baseline APDs and triangular phase 2 profiles. This work demonstrates that the hiPSC-derived CMs are sensitive to low [K + ] Ex and provide a platform to study acquired LQTS. © 2017. Published by The Company of Biologists Ltd.

Comparison of intrapulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and colistin after aerosol delivery and intravenous administration of CMS in critically ill patients.

PubMed

Boisson, Matthieu; Jacobs, Matthieu; Grégoire, Nicolas; Gobin, Patrice; Marchand, Sandrine; Couet, William; Mimoz, Olivier

2014-12-01

Colistin is an old antibiotic that has recently gained a considerable renewal of interest for the treatment of pulmonary infections due to multidrug-resistant Gram-negative bacteria. Nebulization seems to be a promising form of administration, but colistin is administered as an inactive prodrug, colistin methanesulfonate (CMS); however, differences between the intrapulmonary concentrations of the active moiety as a function of the route of administration in critically ill patients have not been precisely documented. In this study, CMS and colistin concentrations were measured on two separate occasions within the plasma and epithelial lining fluid (ELF) of critically ill patients (n = 12) who had received 2 million international units (MIU) of CMS by aerosol delivery and then intravenous administration. The pharmacokinetic analysis was conducted using a population approach and completed by pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulations. The ELF colistin concentrations varied considerably (9.53 to 1,137 mg/liter), but they were much higher than those in plasma (0.15 to 0.73 mg/liter) after aerosol delivery but not after intravenous administration of CMS. Following CMS aerosol delivery, typically, 9% of the CMS dose reached the ELF, and only 1.4% was presystemically converted into colistin. PK-PD analysis concluded that there was much higher antimicrobial efficacy after CMS aerosol delivery than after intravenous administration. These new data seem to support the use of aerosol delivery of CMS for the treatment of pulmonary infections in critical care patients. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Comparison of Intrapulmonary and Systemic Pharmacokinetics of Colistin Methanesulfonate (CMS) and Colistin after Aerosol Delivery and Intravenous Administration of CMS in Critically Ill Patients

PubMed Central

Boisson, Matthieu; Jacobs, Matthieu; Grégoire, Nicolas; Gobin, Patrice; Marchand, Sandrine; Mimoz, Olivier

2014-01-01

Colistin is an old antibiotic that has recently gained a considerable renewal of interest for the treatment of pulmonary infections due to multidrug-resistant Gram-negative bacteria. Nebulization seems to be a promising form of administration, but colistin is administered as an inactive prodrug, colistin methanesulfonate (CMS); however, differences between the intrapulmonary concentrations of the active moiety as a function of the route of administration in critically ill patients have not been precisely documented. In this study, CMS and colistin concentrations were measured on two separate occasions within the plasma and epithelial lining fluid (ELF) of critically ill patients (n = 12) who had received 2 million international units (MIU) of CMS by aerosol delivery and then intravenous administration. The pharmacokinetic analysis was conducted using a population approach and completed by pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulations. The ELF colistin concentrations varied considerably (9.53 to 1,137 mg/liter), but they were much higher than those in plasma (0.15 to 0.73 mg/liter) after aerosol delivery but not after intravenous administration of CMS. Following CMS aerosol delivery, typically, 9% of the CMS dose reached the ELF, and only 1.4% was presystemically converted into colistin. PK-PD analysis concluded that there was much higher antimicrobial efficacy after CMS aerosol delivery than after intravenous administration. These new data seem to support the use of aerosol delivery of CMS for the treatment of pulmonary infections in critical care patients. PMID:25267660

Atrial natriuretic peptide and red cell 2,3-diphosphoglycerate in patients with chronic mountain sickness.

PubMed

Ge, R L; Shai, H R; Takeoka, M; Hanaoka, M; Koizumi, T; Matsuzawa, Y; Kubo, K; Kobayashi, T

2001-01-01

Individuals with chronic mountain sickness (CMS) show severe hypoxemia, excessive polycythemia, and marked pulmonary hypertension. The pathophysiologic mechanisms of CMS are still not completely understood. We determined plasma atrial natriuretic peptide (ANP), red cell 2,3-diphosphoglycerate (2,3-DPG), hematocrit, hemoglobin, and arterialized ear lobe blood gas values in 13 patients with CMS (9 Hans, 4 Tibetans) and 18 control Han Chinese men of similar age, height, and weight who had been living at 4300 m on the Tibetan plateau of Qinghai Province, China, for approximately 14 years. A significantly higher level of ANP was found in the CMS patients compared to the non-CMS patients (113.4+/-5.5 pg/mL vs 87.6+/-4.7 pg/mL, P < .01), and the levels of ANP correlated positively with the hemoglobin concentration (r = 0.8282, P < .01). The 2,3-DPG levels in the CMS patients were significantly increased compared to the non-CMS subjects (5.23+/-0.16 mmol/L vs 4.40+/-0.12 mmol/L, P < .01), and the 2,3-DPG concentrations in the CMS patients were negatively correlated with their PaO2 values (r = -0.7898, P < .01). The CMS patients had significantly higher PaCO2 levels, lower pH values, lower PaO2 levels, and greater alveolar-arterial oxygen differences (PAO2 - PaO2) compared to the non-CMS subjects. These findings suggest that overproduction of ANP and 2,3-DPG at high altitudes may play an important role in the pathophysiology of chronic mountain sickness.

Teaching Health Center Graduate Medical Education Locations Predominantly Located in Federally Designated Underserved Areas.

PubMed

Barclift, Songhai C; Brown, Elizabeth J; Finnegan, Sean C; Cohen, Elena R; Klink, Kathleen

2016-05-01

Background The Teaching Health Center Graduate Medical Education (THCGME) program is an Affordable Care Act funding initiative designed to expand primary care residency training in community-based ambulatory settings. Statute suggests, but does not require, training in underserved settings. Residents who train in underserved settings are more likely to go on to practice in similar settings, and graduates more often than not practice near where they have trained. Objective The objective of this study was to describe and quantify federally designated clinical continuity training sites of the THCGME program. Methods Geographic locations of the training sites were collected and characterized as Health Professional Shortage Area, Medically Underserved Area, Population, or rural areas, and were compared with the distribution of Centers for Medicare and Medicaid Services (CMS)-funded training positions. Results More than half of the teaching health centers (57%) are located in states that are in the 4 quintiles with the lowest CMS-funded resident-to-population ratio. Of the 109 training sites identified, more than 70% are located in federally designated high-need areas. Conclusions The THCGME program is a model that funds residency training in community-based ambulatory settings. Statute suggests, but does not explicitly require, that training take place in underserved settings. Because the majority of the 109 clinical training sites of the 60 funded programs in 2014-2015 are located in federally designated underserved locations, the THCGME program deserves further study as a model to improve primary care distribution into high-need communities.

Treadmill exercise alleviates chronic mild stress-induced depression in rats.

PubMed

Lee, Taeck-Hyun; Kim, Kijeong; Shin, Mal-Soon; Kim, Chang-Ju; Lim, Baek-Vin

2015-12-01

Depression is a major cause of disability and one of the most common public health problems. In the present study, antidepressive effect of treadmill exercise on chronic mild stress (CMS)-induced depression in rats was investigated. For this, sucrose intake test, immunohistochemistry for 5-bromo-2'-deoxyuridine, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining, and Western blot analysis for brain-derived neurotrophic factor, cyclic adenosine monophosphate response element binding protein, and endothelial nitric oxide synthase were conducted. Following adaptation to the animal vivarium and two baseline fluid intake tests, the animals were divided into four groups: the control group, the CMS-induced depression group, the CMS-induced depression and exercise group, and the CMS-induced depression and fluoxetine-treated group. The animals in the CMS groups were exposed to the CMS conditions for 8 weeks and those in the control group were exposed to the control conditions for 8 weeks. After 4 weeks of CMS, the rats in the CMS-induced depression and exercise group were made to run on a motorized treadmill for 30 min once a day for 4 weeks. In the present results, treadmill exercise alleviated CMS-induced depressive symptoms. Treadmill exercise restored sucrose consumption, increased cell proliferation, and decreased apoptotic cell death. The present results suggest the possibility that exercise may improve symptoms of depression.

Carboxymethyl starch mucoadhesive microspheres as gastroretentive dosage form.

PubMed

Lemieux, Marc; Gosselin, Patrick; Mateescu, Mircea Alexandru

2015-12-30

Carboxymethyl starch microspheres (CMS-MS) were produced from carboxymethyl starch powder (CMS-P) with a degree of substitution (DS) from 0.1 to 1.5 in order to investigate the influence of DS on physicochemical, drug release and mucoadhesion properties as well as interactions with gastrointestinal tract (GIT) epithelial barrier models. Placebo and furosemide loaded CMS-MS were obtained by emulsion-crosslinking with sodium trimetaphosphate (STMP). DS had an impact on increasing equilibrium water uptake and modulating drug release properties of the CMS-MS according to the surrounding pH. The transepithelial electrical resistance (TEER) of NCI-N87 gastric cell monolayers was not influenced in presence of CMS-MS, whereas that of Caco-2 intestinal cell monolayers decreased with increasing DS but recovered initial values at about 15h post-treatment. CMS-MS with increasing DS also enhanced furosemide permeability across both NCI-N87 and Caco-2 monolayers at pH gradients from 3.0 to 7.4. Mucoadhesion of CMS-MS on gastric mucosa (acidic condition) increased with the DS up to 55% for a DS of 1.0 but decreased on neutral intestinal mucosa to less than 10% with DS of 0.1. The drug release, permeability enhancement and mucoadhesive properties of the CMS-MS suggest CMS-MS with DS between 0.6 and 1.0 as suitable excipient for gastroretentive oral delivery dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

42 CFR 416.30 - Terms of agreement with CMS.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Terms of agreement with CMS. 416.30 Section 416.30... of agreement with CMS. As part of the agreement under § 416.26 the ASC must agree to the following... in subpart C of this part and to report promptly to CMS any failure to do so. (b) Limitation on...

Evaluation of Using Course-Management Software: Supplementing a Course that Requires a Group Research Project

ERIC Educational Resources Information Center

Korchmaros, Josephine D.; Gump, Nathaniel W.

2009-01-01

The benefits of course-management software (CMS) will not be realized if it is underused. The authors investigated one possible barrier to CMS use, students' perceptions of using CMS. After taking a course requiring a group research project, college students reported their perceptions of the use of CMS for the course. Overall, students did not…

Recent Highlights of Metabolomics in Chinese Medicine Syndrome Research

PubMed Central

Zhang, Ai-hua; Sun, Hui; Qiu, Shi; Wang, Xi-jun

2013-01-01

Chinese medicine syndrome (CMS, “ZHENG” in Chinese) is an understanding of the regularity of disease occurrence and development as well as a certain stage of a comprehensive response of patients with body condition. However, because of the complexity of CMS and the limitation of present investigation method, the research for deciphering the scientific basis and systematic features of CMS is difficult to go further. Metabolomics enables mapping of early biochemical changes in disease and hence provides an opportunity to develop predictive biomarkers. Moreover, its method and design resemble those of traditional Chinese medicine (TCM) which focuses on human disease via the integrity of close relationship between body and syndromes. In the systemic context, metabolomics has a convergence with TCM syndrome; therefore it could provide useful tools for exploring essence of CMS disease, facilitating personalized TCM, and will help to in-depth understand CMS. The integration of the metabolomics and CMS aspects will give promise to bridge the gap between Chinese and Western medicine and help catch the traditional features of CMS. In this paper, particular attention will be paid to the past successes in applications of robust metabolomic approaches to contribute to low-molecular-weight metabolites (biomarkers) discovery in CMS research and development. PMID:24302964

IK1-enhanced human-induced pluripotent stem cell-derived cardiomyocytes: an improved cardiomyocyte model to investigate inherited arrhythmia syndromes

PubMed Central

Vaidyanathan, Ravi; Markandeya, Yogananda S.; Kamp, Timothy J.; Makielski, Jonathan C.; January, Craig T.

2016-01-01

Currently available induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) do not ideally model cellular mechanisms of human arrhythmic disease due to lack of a mature action potential (AP) phenotype. In this study, we create and characterize iPS-CMs with an electrically mature AP induced by potassium inward rectifier (IK1) enhancement. The advantages of IK1-enhanced iPS-CMs include the absence of spontaneous beating, stable resting membrane potentials at approximately −80 mV and capability for electrical pacing. Compared with unenhanced, IK1-enhanced iPS-CMs calcium transient amplitudes were larger (P < 0.05) with a typical staircase pattern. IK1-enhanced iPS-CMs demonstrated a twofold increase in cell size and membrane capacitance and increased DNA synthesis compared with control iPS-CMs (P < 0.05). Furthermore, IK1-enhanced iPS-CMs expressing the F97C-CAV3 long QT9 mutation compared with wild-type CAV3 demonstrated an increase in AP duration and late sodium current. IK1-enhanced iPS-CMs represent a more mature cardiomyocyte model to study arrhythmia mechanisms. PMID:27059077

CMS Analysis School Model

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

Malik, S.; Shipsey, I.; Cavanaugh, R.

To impart hands-on training in physics analysis, CMS experiment initiated the concept of CMS Data Analysis School (CMSDAS). It was born over three years ago at the LPC (LHC Physics Centre), Fermilab and is based on earlier workshops held at the LPC and CLEO Experiment. As CMS transitioned from construction to the data taking mode, the nature of earlier training also evolved to include more of analysis tools, software tutorials and physics analysis. This effort epitomized as CMSDAS has proven to be a key for the new and young physicists to jump start and contribute to the physics goals ofmore » CMS by looking for new physics with the collision data. With over 400 physicists trained in six CMSDAS around the globe, CMS is trying to engage the collaboration in its discovery potential and maximize physics output. As a bigger goal, CMS is striving to nurture and increase engagement of the myriad talents, in the development of physics, service, upgrade, education of those new to CMS and the career development of younger members. An extension of the concept to the dedicated software and hardware schools is also planned, keeping in mind the ensuing upgrade phase.« less

Low Resting Membrane Potential and Low Inward Rectifier Potassium Currents Are Not Inherent Features of hiPSC-Derived Cardiomyocytes.

PubMed

Horváth, András; Lemoine, Marc D; Löser, Alexandra; Mannhardt, Ingra; Flenner, Frederik; Uzun, Ahmet Umur; Neuber, Christiane; Breckwoldt, Kaja; Hansen, Arne; Girdauskas, Evaldas; Reichenspurner, Hermann; Willems, Stephan; Jost, Norbert; Wettwer, Erich; Eschenhagen, Thomas; Christ, Torsten

2018-03-13

Human induced pluripotent stem cell (hiPSC) cardiomyocytes (CMs) show less negative resting membrane potential (RMP), which is attributed to small inward rectifier currents (I K1 ). Here, I K1 was measured in hiPSC-CMs (proprietary and commercial cell line) cultured as monolayer (ML) or 3D engineered heart tissue (EHT) and, for direct comparison, in CMs from human right atrial (RA) and left ventricular (LV) tissue. RMP was measured in isolated cells and intact tissues. I K1 density in ML- and EHT-CMs from the proprietary line was similar to LV and RA, respectively. I K1 density in EHT-CMs from the commercial line was 2-fold smaller than in the proprietary line. RMP in EHT of both lines was similar to RA and LV. Repolarization fraction and I K,ACh response discriminated best between RA and LV and indicated predominantly ventricular phenotype in hiPSC-CMs/EHT. The data indicate that I K1 is not necessarily low in hiPSC-CMs, and technical issues may underlie low RMP in hiPSC-CMs. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Cerebral cavernous malformations: natural history and clinical management.

PubMed

Gross, Bradley A; Du, Rose

2015-01-01

Cavernous malformations (CMs) are angiographically-occult clusters of dilated sinusoidal channels that may present clinically with seizures, focal neurological deficits and/or hemorrhage. Across natural history studies, the annual hemorrhage rate ranged from 1.6-3.1% per patient-year, decreasing to 0.08-0.2% per patient-year for incidental CMs and to 0.3-0.6% for the collective group of unruptured CMs. Prior hemorrhage is a significant risk factor for subsequent CM hemorrhage. Hemorrhage clustering, particularly within the first 2 years, is an established phenomenon that may confound results of natural history studies evaluating the rate of rehemorrhage. Indeed, rehemorrhage rates for hemorrhagic CMs range from 4.5-22.9% in the literature. Surgical resection is the gold standard treatment for surgically-accessible, symptomatic CMs. Incidental CMs or minimally symptomatic, surgically inaccessible eloquent lesions may be considered for observation. Stereotactic radiosurgery is a controversial treatment approach of consideration only for cases of highly aggressive, surgically inaccessible CMs.

The CMS dataset bookkeeping service

NASA Astrophysics Data System (ADS)

Afaq, A.; Dolgert, A.; Guo, Y.; Jones, C.; Kosyakov, S.; Kuznetsov, V.; Lueking, L.; Riley, D.; Sekhri, V.

2008-07-01

The CMS Dataset Bookkeeping Service (DBS) has been developed to catalog all CMS event data from Monte Carlo and Detector sources. It provides the ability to identify MC or trigger source, track data provenance, construct datasets for analysis, and discover interesting data. CMS requires processing and analysis activities at various service levels and the DBS system provides support for localized processing or private analysis, as well as global access for CMS users at large. Catalog entries can be moved among the various service levels with a simple set of migration tools, thus forming a loose federation of databases. DBS is available to CMS users via a Python API, Command Line, and a Discovery web page interfaces. The system is built as a multi-tier web application with Java servlets running under Tomcat, with connections via JDBC to Oracle or MySQL database backends. Clients connect to the service through HTTP or HTTPS with authentication provided by GRID certificates and authorization through VOMS. DBS is an integral part of the overall CMS Data Management and Workflow Management systems.

Influence of off-stoichiometry on magnetoresistance characteristics of Co2MnSi/Ag-based current-perpendicular-to-plane spin valves

NASA Astrophysics Data System (ADS)

Inoue, Masaki; Hu, Bing; Moges, Kidist; Inubushi, Kazuumi; Nakada, Katsuyuki; Yamamoto, Masafumi; Uemura, Tetsuya

2017-08-01

The influence of off-stoichiometry of Co2MnSi (CMS) spin sources on giant magnetoresistance characteristics was investigated for CMS/Ag-based current-perpendicular-to-plane spin valves prepared with various Mn compositions α in Co2MnαSi0.82 electrodes. The magnetoresistance ratio of the prepared CMS/Co50Fe50 (CoFe) (1.1 nm)/Ag/CoFe (1.1)/CMS spin valves systematically increased with α from 11.4% for Mn-deficient α = 0.62 to 20.7% for Mn-rich α = 1.45 at 290 K. This result suggests that increasing α from a Mn-deficient to Mn-rich value increases the spin polarization by suppressing CoMn antisites harmful to the half-metallicity. Thus, our results demonstrate that appropriately controlling the film composition toward a Mn-rich one is highly effective for enhancing the half-metallicity of CMS in CMS-based spin valves, as it is in CMS-based magnetic tunnel junctions.

Extracellular Recordings of Patterned Human Pluripotent Stem Cell-Derived Cardiomyocytes on Aligned Fibers.

PubMed

Li, Junjun; Minami, Itsunari; Yu, Leqian; Tsuji, Kiyotaka; Nakajima, Minako; Qiao, Jing; Suzuki, Masato; Shimono, Ken; Nakatsuji, Norio; Kotera, Hitetoshi; Liu, Li; Chen, Yong

2016-01-01

Human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (CMs) hold high potential for use in drug assessment and myocardial regeneration. To create tissue-like constructs of CMs for extracellular monitoring, we placed aligned fibers (AFs) on the surface of a microelectrode array and then seeded hiPSC-CMs for subsequent monitoring for 14 days. As expected, the CMs organized into anisotropic and matured tissue and the extracellular recordings showed reduced premature beating higher signal amplitude and a higher probability of T-wave detection as compared to the culture without fibers. The CMs on the aligned fibers samples also exhibited anisotropic propagation of the field potential. These results therefore suggest that the hiPSC-CMs cultured on AFs can be used more reliably for cell based assays.

Extracellular Recordings of Patterned Human Pluripotent Stem Cell-Derived Cardiomyocytes on Aligned Fibers

PubMed Central

Minami, Itsunari; Yu, Leqian; Nakajima, Minako; Qiao, Jing; Shimono, Ken; Nakatsuji, Norio; Kotera, Hitetoshi; Chen, Yong

2016-01-01

Human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (CMs) hold high potential for use in drug assessment and myocardial regeneration. To create tissue-like constructs of CMs for extracellular monitoring, we placed aligned fibers (AFs) on the surface of a microelectrode array and then seeded hiPSC-CMs for subsequent monitoring for 14 days. As expected, the CMs organized into anisotropic and matured tissue and the extracellular recordings showed reduced premature beating higher signal amplitude and a higher probability of T-wave detection as compared to the culture without fibers. The CMs on the aligned fibers samples also exhibited anisotropic propagation of the field potential. These results therefore suggest that the hiPSC-CMs cultured on AFs can be used more reliably for cell based assays. PMID:27446217

Pollen developmental defects in ZD-CMS rice line explored by cytological, molecular and proteomic approaches.

PubMed

Yan, Junjie; Tian, Han; Wang, Shuzhen; Shao, Jinzhen; Zheng, Yinzhen; Zhang, Hongyuan; Guo, Lin; Ding, Yi

2014-08-28

Cytoplasmic male sterility (CMS) is a widely observed phenomenon, which is especially useful in hybrid seed production. Meixiang A (MxA) is a new rice CMS line derived from a pollen-free sterile line named Yunnan ZidaoA (ZD-CMS). In this study, a homologous WA352 gene with variation in two nucleotides was identified in MxA. Cytological analysis revealed that MxA was aborted in the early uninucleate stage. The protein expression profiles of MxA and its maintainer line MeixiangB (MxB) were systematically compared using iTRAQ-based quantitative proteomics technology using young florets at the early uninucleate stage. A total of 688 proteins were quantified in both rice lines, and 45 of these proteins were found to be differentially expressed. Bioinformatics analysis indicated a large number of the proteins involved in carbohydrate metabolism or the stress response were downregulated in MxA, suggesting that these metabolic processes had been hindered during pollen development in MxA. The ROS (reactive oxygen species) level was increased in the mitochondrion of MxA, and further ultrastructural analysis showed the mitochondria with disrupted cristae in the rice CMS line MxA. These findings substantially contribute to our knowledge of pollen developmental defects in ZD-CMS rice line. MeixiangA (MxA) is a new type of rice CMS line, which is derived from pollen-free sterile line Yunnan ZidaoA. In this study, the cytological, molecular and proteomic approaches were used to study the characteristics of this new CMS line. Cytological study indicates the CMS line is aborted at the early uninucleate stage. A potential sterile gene ZD352 is identified in MxA, the protein product of which is mainly accumulated at the MMC/Meiotic stage. iTRAQ based proteomic analysis is performed to study the relevant proteins involved in the CMS occurance, 45 proteins are found to be significant differentially expressed and these proteins are involved in many cellular processes such as carbohydrate metabolism, stress response, protein synthesis. To our knowledge, this is the first report using the iTRAQ-labeled quantitative proteomic to study the protein expression variation during the abortion processes between a CMS line and its maintainer line. These results provide new insights on the CMS mechanisms of ZD-CMS rice line. Copyright © 2014 Elsevier B.V. All rights reserved.

Physics Goals and Experimental Challenges of the Proton-Proton High-Luminosity Operation of the LHC

NASA Astrophysics Data System (ADS)

Campana, P.; Klute, M.; Wells, P. S.

2016-10-01

The completion of Run 1 of the Large Hadron Collider (LHC) at CERN has seen the discovery of the Higgs boson and an unprecedented number of precise measurements of the Standard Model, and Run 2 has begun to provide the first data at higher energy. The high-luminosity upgrade of the LHC (HL-LHC) and the four experiments (ATLAS, CMS, ALICE, and LHCb) will exploit the full potential of the collider to discover and explore new physics beyond the Standard Model. We review the experimental challenges and the physics opportunities in proton-proton collisions at the HL-LHC.

42 CFR 405.1010 - When CMS or its contractors may participate in an ALJ hearing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false When CMS or its contractors may participate in an... Hearings § 405.1010 When CMS or its contractors may participate in an ALJ hearing. (a) An ALJ may request, but may not require, CMS and/or one or more of its contractors to participate in any proceedings...

Particle Tracking Model (PTM) with Coastal Modeling System (CMS)

DTIC Science & Technology

2015-11-04

Coastal Inlets Research Program Particle Tracking Model (PTM) with Coastal Modeling System ( CMS ) The Particle Tracking Model (PTM) is a Lagrangian...currents and waves. The Coastal Inlets Research Program (CIRP) supports the PTM with the Coastal Modeling System ( CMS ), which provides coupled wave...and current forcing for PTM simulations. CMS -PTM is implemented in the Surface-water Modeling System, a GUI environment for input development

Challenges to Software/Computing for Experimentation at the LHC

NASA Astrophysics Data System (ADS)

Banerjee, Sunanda

The demands of future high energy physics experiments towards software and computing have led the experiments to plan the related activities as a full-fledged project and to investigate new methodologies and languages to meet the challenges. The paths taken by the four LHC experiments ALICE, ATLAS, CMS and LHCb are coherently put together in an LHC-wide framework based on Grid technology. The current status and understandings have been broadly outlined.

Identification of mitochondrial DNA sequence variation and development of single nucleotide polymorphic markers for CMS-D8 in cotton.

PubMed

Suzuki, Hideaki; Yu, Jiwen; Wang, Fei; Zhang, Jinfa

2013-06-01

Cytoplasmic male sterility (CMS), which is a maternally inherited trait and controlled by novel chimeric genes in the mitochondrial genome, plays a pivotal role in the production of hybrid seed. In cotton, no PCR-based marker has been developed to discriminate CMS-D8 (from Gossypium trilobum) from its normal Upland cotton (AD1, Gossypium hirsutum) cytoplasm. The objective of the current study was to develop PCR-based single nucleotide polymorphic (SNP) markers from mitochondrial genes for the CMS-D8 cytoplasm. DNA sequence variation in mitochondrial genes involved in the oxidative phosphorylation chain including ATP synthase subunit 1, 4, 6, 8 and 9, and cytochrome c oxidase 1, 2 and 3 subunits were identified by comparing CMS-D8, its isogenic maintainer and restorer lines on the same nuclear genetic background. An allelic specific PCR (AS-PCR) was utilized for SNP typing by incorporating artificial mismatched nucleotides into the third or fourth base from the 3' terminus in both the specific and nonspecific primers. The result indicated that the method modifying allele-specific primers was successful in obtaining eight SNP markers out of eight SNPs using eight primer pairs to discriminate two alleles between AD1 and CMS-D8 cytoplasms. Two of the SNPs for atp1 and cox1 could also be used in combination to discriminate between CMS-D8 and CMS-D2 cytoplasms. Additionally, a PCR-based marker from a nine nucleotide insertion-deletion (InDel) sequence (AATTGTTTT) at the 59-67 bp positions from the start codon of atp6, which is present in the CMS and restorer lines with the D8 cytoplasm but absent in the maintainer line with the AD1 cytoplasm, was also developed. A SNP marker for two nucleotide substitutions (AA in AD1 cytoplasm to CT in CMS-D8 cytoplasm) in the intron (1,506 bp) of cox2 gene was also developed. These PCR-based SNP markers should be useful in discriminating CMS-D8 and AD1 cytoplasms, or those with CMS-D2 cytoplasm as a rapid, simple, inexpensive, and reliable genotyping tool to assist hybrid cotton breeding.

CMS-dependent prognostic impact of KRAS and BRAFV600E mutations in primary colorectal cancer.

PubMed

Smeby, J; Sveen, A; Merok, M A; Danielsen, S A; Eilertsen, I A; Guren, M G; Dienstmann, R; Nesbakken, A; Lothe, R A

2018-05-01

The prognostic impact of KRAS and BRAFV600E mutations in primary colorectal cancer (CRC) varies with microsatellite instability (MSI) status. The gene expression-based consensus molecular subtypes (CMSs) of CRC define molecularly and clinically distinct subgroups, and represent a novel stratification framework in biomarker analysis. We investigated the prognostic value of these mutations within the CMS groups. Totally 1197 primary tumors from a Norwegian series of CRC stage I-IV were analyzed for MSI and mutation status in hotspots in KRAS (codons 12, 13 and 61) and BRAF (codon 600). A subset was analyzed for gene expression and confident CMS classification was obtained for 317 samples. This cohort was expanded with clinical and molecular data, including CMS classification, from 514 patients in the publically available dataset GSE39582. Gene expression signatures associated with KRAS and BRAFV600E mutations were used to evaluate differential impact of mutations on gene expression among the CMS groups. BRAFV600E and KRAS mutations were both associated with inferior 5-year overall survival (OS) exclusively in MSS tumors (BRAFV600E mutation versus KRAS/BRAF wild-type: Hazard ratio (HR) 2.85, P < 0.001; KRAS mutation versus KRAS/BRAF wild-type: HR 1.30, P = 0.013). BRAFV600E-mutated MSS tumors were strongly enriched and associated with metastatic disease in CMS1, leading to negative prognostic impact in this subtype (OS: BRAFV600E mutation versus wild-type: HR 7.73, P = 0.001). In contrast, the poor prognosis of KRAS mutations was limited to MSS tumors with CMS2/CMS3 epithelial-like gene expression profiles (OS: KRAS mutation versus wild-type: HR 1.51, P = 0.011). The subtype-specific prognostic associations were substantiated by differential effects of BRAFV600E and KRAS mutations on gene expression signatures according to the MSI status and CMS group. BRAFV600E mutations are enriched and associated with metastatic disease in CMS1 MSS tumors, leading to poor prognosis in this subtype. KRAS mutations are associated with adverse outcome in epithelial (CMS2/CMS3) MSS tumors.

Effective Hypothermic Storage of Human Pluripotent Stem Cell-Derived Cardiomyocytes Compatible With Global Distribution of Cells for Clinical Applications and Toxicology Testing

PubMed Central

Correia, Cláudia; Koshkin, Alexey; Carido, Madalena; Espinha, Nuno; Šarić, Tomo; Lima, Pedro A.; Alves, Paula M.

2016-01-01

To fully explore the potential of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), efficient methods for storage and shipment of these cells are required. Here, we evaluated the feasibility to cold store monolayers and aggregates of functional CMs obtained from different PSC lines using a fully defined clinical-compatible preservation formulation and investigated the time frame that hPSC-CMs could be subjected to hypothermic storage. We showed that two-dimensional (2D) monolayers of hPSC-CMs can be efficiently stored at 4°C for 3 days without compromising cell viability. However, cell viability decreased when the cold storage interval was extended to 7 days. We demonstrated that hPSC-CMs are more resistant to prolonged hypothermic storage-induced cell injury in three-dimensional aggregates than in 2D monolayers, showing high cell recoveries (>70%) after 7 days of storage. Importantly, hPSC-CMs maintained their typical (ultra)structure, gene and protein expression profile, electrophysiological profiles, and drug responsiveness. Significance The applicability of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) in the clinic/industry is highly dependent on the development of efficient methods for worldwide shipment of these cells. This study established effective clinically compatible strategies for cold (4°C) storage of hPSC-CMs cultured as two-dimensional (2D) monolayers and three-dimensional (3D) aggregates. Cell recovery of 2D monolayers of hPSC-CMs was found to be dependent on the time of storage, and 3D cell aggregates were more resistant to prolonged cold storage than 2D monolayers. Of note, it was demonstrated that 7 days of cold storage did not affect hPSC-CM ultrastructure, phenotype, or function. This study provides important insights into the cold preservation of PSC-CMs that could be valuable in improving global commercial distribution of hPSC-CMs. PMID:27025693

Effective Hypothermic Storage of Human Pluripotent Stem Cell-Derived Cardiomyocytes Compatible With Global Distribution of Cells for Clinical Applications and Toxicology Testing.

PubMed

Correia, Cláudia; Koshkin, Alexey; Carido, Madalena; Espinha, Nuno; Šarić, Tomo; Lima, Pedro A; Serra, Margarida; Alves, Paula M

2016-05-01

To fully explore the potential of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), efficient methods for storage and shipment of these cells are required. Here, we evaluated the feasibility to cold store monolayers and aggregates of functional CMs obtained from different PSC lines using a fully defined clinical-compatible preservation formulation and investigated the time frame that hPSC-CMs could be subjected to hypothermic storage. We showed that two-dimensional (2D) monolayers of hPSC-CMs can be efficiently stored at 4°C for 3 days without compromising cell viability. However, cell viability decreased when the cold storage interval was extended to 7 days. We demonstrated that hPSC-CMs are more resistant to prolonged hypothermic storage-induced cell injury in three-dimensional aggregates than in 2D monolayers, showing high cell recoveries (>70%) after 7 days of storage. Importantly, hPSC-CMs maintained their typical (ultra)structure, gene and protein expression profile, electrophysiological profiles, and drug responsiveness. The applicability of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) in the clinic/industry is highly dependent on the development of efficient methods for worldwide shipment of these cells. This study established effective clinically compatible strategies for cold (4°C) storage of hPSC-CMs cultured as two-dimensional (2D) monolayers and three-dimensional (3D) aggregates. Cell recovery of 2D monolayers of hPSC-CMs was found to be dependent on the time of storage, and 3D cell aggregates were more resistant to prolonged cold storage than 2D monolayers. Of note, it was demonstrated that 7 days of cold storage did not affect hPSC-CM ultrastructure, phenotype, or function. This study provides important insights into the cold preservation of PSC-CMs that could be valuable in improving global commercial distribution of hPSC-CMs. ©AlphaMed Press.

45 CFR 150.213 - Form and content of notice.

Code of Federal Regulations, 2013 CFR

2013-10-01

... CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for Determining... information that the State wishes CMS to consider in making the preliminary determination described in § 150...

45 CFR 150.213 - Form and content of notice.

Code of Federal Regulations, 2012 CFR

2012-10-01

... CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for Determining... information that the State wishes CMS to consider in making the preliminary determination described in § 150...

ATLAS, CMS and new challenges for public communication

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

Taylor, Lucas; Barney, David; Goldfarb, Steven

On 30 March 2010 the first high-energy collisions brought the LHC experiments into the era of research and discovery. Millions of viewers worldwide tuned in to the webcasts and followed the news via Web 2.0 tools, such as blogs, Twitter, and Facebook, with 205,000 unique visitors to CERN's Web site. Media coverage at the experiments and in institutes all over the world yielded more than 2,200 news items including 800 TV broadcasts. We describe the new multimedia communications challenges, due to the massive public interest in the LHC programme, and the corresponding responses of the ATLAS and CMS experiments, inmore » the areas of Web 2.0 tools, multimedia, webcasting, videoconferencing, and collaborative tools. We discuss the strategic convergence of the two experiments' communications services, information systems and public database of outreach material.« less

ATLAS, CMS and New Challenges for Public Communication

NASA Astrophysics Data System (ADS)

Taylor, Lucas; Barney, David; Goldfarb, Steven

2011-12-01

On 30 March 2010 the first high-energy collisions brought the LHC experiments into the era of research and discovery. Millions of viewers worldwide tuned in to the webcasts and followed the news via Web 2.0 tools, such as blogs, Twitter, and Facebook, with 205,000 unique visitors to CERN's Web site. Media coverage at the experiments and in institutes all over the world yielded more than 2,200 news items including 800 TV broadcasts. We describe the new multimedia communications challenges, due to the massive public interest in the LHC programme, and the corresponding responses of the ATLAS and CMS experiments, in the areas of Web 2.0 tools, multimedia, webcasting, videoconferencing, and collaborative tools. We discuss the strategic convergence of the two experiments' communications services, information systems and public database of outreach material.

Chronic Mild Stress Alters Kynurenine Pathways Changing the Glutamate Neurotransmission in Frontal Cortex of Rats.

PubMed

Martín-Hernández, David; Tendilla-Beltrán, Hiram; Madrigal, José L M; García-Bueno, Borja; Leza, Juan C; Caso, Javier R

2018-05-03

Immune stimulation might be involved in the pathophysiology of major depressive disorder (MDD). This stimulation induces indoleamine 2,3-dioxygenase (IDO), an enzyme that reduces the tryptophan bioavailability to synthesize serotonin. IDO products, kynurenine metabolites, exert neurotoxic/neuroprotective actions through glutamate receptors. Thus, we study elements of these pathways linked to kynurenine metabolite activity examining whether antidepressants (ADs) can modulate them. Male Wistar rats were exposed to chronic mild stress (CMS), and some of them were treated with ADs. The expression of elements of the IDO pathway, including kynurenine metabolites, and their possible modulation by ADs was studied in the frontal cortex (FC). CMS increased IDO expression in FC compared to control group, and ADs restored the IDO expression levels to control values. CMS-induced IDO expression led to increased levels of the excitotoxic quinolinic acid (QUINA) compared to control, and ADs prevented the rise in such levels. Neither CMS nor ADs changed significantly the antiexcitotoxic kynurenic acid (KYNA) levels. The QUINA/KYNA ratio, calculated as excitotoxicity risk indicator, increased after CMS and ADs prevented this increase. CMS lowered excitatory amino acid transporter (EAAT)-1 and EAAT-4 expression, and some ADs restored their expression levels. Furthermore, CMS decreased N-methyl-D-aspartate receptor (NMDAR)-2A and 2B protein expression, and ADs mitigated this decrease. Our research examines the link between CMS-induced pro-inflammatory cytokines and the kynurenine pathway; it shows that CMS alters the kynurenine pathway in rat FC. Importantly, it also reveals the ability of classic ADs to prevent potentially harmful situations related to the brain scenario caused by CMS.

Post-operative paediatric cerebellar mutism syndrome: time to move beyond structural MRI.

PubMed

Toescu, Sebastian M; Hettige, Samantha; Phipps, Kim; Smith, R J Paul; Haffenden, Verity; Clark, Chris; Hayward, Richard; Mankad, Kshitij; Aquilina, Kristian

2018-06-20

To determine the value of structural magnetic resonance imaging (MRI) in predicting post-operative paediatric cerebellar mutism syndrome (pCMS) in children undergoing surgical treatment for medulloblastoma. Retrospective cohort study design. Electronic/paper case note review of all children with medulloblastoma presenting to Great Ormond Street Hospital between 2003 and 2013. The diagnosis of pCMS was established through a scoring system incorporating mutism, ataxia, behavioural disturbance and cranial nerve deficits. MRI scans performed at three time points were assessed by neuroradiologists blinded to the diagnosis of pCMS. Of 56 children included, 12 (21.4%) developed pCMS as judged by a core symptom of mutism. pCMS was more common in those aged 5 or younger. There was no statistically significant difference in pre-operative distortion or signal change of the dentate or red nuclei or superior cerebellar peduncles (SCPs) between those who did and did not develop pCMS. In both early (median 5 days) and late (median 31 months) post-operative scans, T2-weighted signal change in SCPs was more common in the pCMS group (p = 0.040 and 0.046 respectively). Late scans also showed statistically significant signal change in the dentate nuclei (p = 0.024). The development of pCMS could not be linked to any observable changes on pre-operative structural MRI scans. Post-operative T2-weighted signal change in the SCPs and dentate nuclei underlines the role of cerebellar efferent injury in pCMS. Further research using advanced quantitative MRI sequences is warranted given the inability of conventional pre-surgical MRI to predict pCMS.

Transcriptome analysis of cytoplasmic male sterility and restoration in CMS-D8 cotton.

PubMed

Suzuki, Hideaki; Rodriguez-Uribe, Laura; Xu, Jiannong; Zhang, Jinfa

2013-10-01

A global view of differential expression of genes in CMS-D8 of cotton was presented in this study which will facilitate the understanding of cytoplasmic male sterility in cotton. Cytoplasmic male sterility (CMS) is a maternally inherited trait in higher plants which is incapable of producing functional pollen. However, the male fertility can be restored by one or more nuclear-encoded restorer genes. A genome-wide transcriptome analysis of CMS and restoration in cotton is currently lacking. In this study, Affymetrix GeneChips© Cotton Genome Array containing 24,132 transcripts was used to compare differentially expressed (DE) genes of flower buds at the meiosis stage between CMS and its restorer cotton plants conditioned by the D8 cytoplasm. A total of 458 (1.9 %) of DE genes including 127 up-regulated and 331 down-regulated ones were identified in the CMS-D8 line. Quantitative RT-PCR was used to validate 10 DE genes selected from seven functional categories. The most frequent DE gene group was found to encode putative proteins involved in cell wall expansion, such as pectinesterase, pectate lyase, pectin methylesterase, glyoxal oxidase, polygalacturonase, indole-3-acetic acid-amino synthetase, and xyloglucan endo-transglycosylase. Genes in cytoskeleton category including actin, which plays a key role in cell wall expansion, cell elongation and cell division, were also highly differentially expressed between the fertile and CMS plants. This work represents the first study in utilizing microarray to identify CMS-related genes by comparing overall DE genes between fertile and CMS plants in cotton. The results provide evidence that many CMS-associated genes are mainly involved in cell wall expansion. Further analysis will be required to elucidate the molecular mechanisms of male sterility which will facilitate the development of new hybrid cultivars in cotton.

Congenital myasthenic syndromes in Turkey: Clinical clues and prognosis with long term follow-up.

PubMed

Durmus, Hacer; Shen, Xin-Ming; Serdaroglu-Oflazer, Piraye; Kara, Bulent; Parman-Gulsen, Yesim; Ozdemir, Coskun; Brengman, Joan; Deymeer, Feza; Engel, Andrew G

2018-04-01

Congenital myasthenic syndromes (CMS) are a group of hereditary disorders affecting the neuromuscular junction. Here, we present clinical, electrophysiological and genetic findings of 69 patients from 51 unrelated kinships from Turkey. Genetic tests of 60 patients were performed at Mayo Clinic. Median follow-up time was 9.8 years (range 1-22 years). The most common CMS was primary acetylcholine receptor (AChR) deficiency (31/51) and the most common mutations in AChR were c.1219 + 2T > G (12/51) and c.1327delG (6/51) in CHRNE. Four of our 5 kinships with AChE deficiency carried p.W148X that truncates the collagen domain of COLQ, and was previously reported only in patients from Turkey. These were followed by GFPT1 deficiency (4/51), DOK7 deficiency (3/51), slow channel CMS (3/51), fast channel CMS (3/51), choline acetyltransferase deficiency (1/51) and a CMS associated with desmin deficiency (1/51). Distribution of muscle weakness was sometimes useful in giving a clue to the CMS subtype. Presence of repetitive compound muscle action potentials pointed to AChE deficiency or slow channel CMS. Our experience confirms that one needs to be cautious using pyridostigmine, since it can worsen some types of CMS. Ephedrine/salbutamol were very effective in AChE and DOK7 deficiencies and were useful as adjuncts in other types of CMS. Long follow-up gave us a chance to assess progression of the disease, and to witness 12 mainly uneventful pregnancies in 8 patients. In this study, we describe some new phenotypes and detail the clinical features of the well-known CMS. Copyright © 2017 Elsevier B.V. All rights reserved.

Purification of Cardiomyocytes from Differentiating Pluripotent Stem Cells using Molecular Beacons Targeting Cardiomyocyte-Specific mRNA

PubMed Central

Kim, Sangsung; Park, Hun-Jun; Byun, Jaemin; Cho, Kyu-Won; Saafir, Talib; Song, Ming-Ke; Yu, Shan Ping; Wagner, Mary; Bao, Gang; Yoon, Young-Sup

2013-01-01

Background While methods for generating cardiomyocytes (CMs) from pluripotent stem cells (PSCs) have been reported, current methods produce heterogeneous mixtures of CMs and non-CM cells. Here, we report an entirely novel system in which PSC-derived CMs are purified by CM-specific molecular beacons (MBs). MBs are nano-scale probes that emit a fluorescence signal when hybridized to target mRNAs. Method and Results Five MBs targeting mRNAs of either cardiac troponin T or myosin heavy chain 6/7 were generated. Among five MBs, a MB targeting myosin heavy chain 6/7 mRNA (MHC1-MB) identified up to 99% of HL-1 CMs, a mouse CM cell line, but < 3% of four non-CM cell types in flow cytometry analysis, indicating that MHC1-MB is specific for identifying CMs. We delivered MHC1-MB into cardiomyogenically differentiated PSCs through nucleofection. The detection rate of CMs was similar to the percentages of cardiac troponin T (TNNT2) or cardiac troponin I (TNNI3)-positive CMs, supporting the specificity of MBs. Finally, MHC1-MB-positive cells were FACS-sorted from mouse and human PSC differentiating cultures and ~97% cells expressed TNNT2- or TNNI3 determined by flow cytometry. These MB-based sorted cells maintained their CM characteristics verified by spontaneous beating, electrophysiologic studies, and expression of cardiac proteins. When transplanted in a myocardial infarction model, MB-based purified CMs improved cardiac function and demonstrated significant engraftment for 4 weeks without forming tumors. Conclusions We developed a novel CM selection system that allows production of highly purified CMs. These purified CMs and this system can be valuable for cell therapy and drug discovery. PMID:23995537

Reporting trends and outcomes in ST-segment-elevation myocardial infarction national hospital quality assessment programs.

PubMed

McCabe, James M; Kennedy, Kevin F; Eisenhauer, Andrew C; Waldman, Howard M; Mort, Elizabeth A; Pomerantsev, Eugene; Resnic, Frederic S; Yeh, Robert W

2014-01-14

For patients who undergo primary percutaneous coronary intervention (PCI) for ST-segment-elevation myocardial infarction, the door-to-balloon time is an important performance measure reported to the Centers for Medicare & Medicaid Services (CMS) and tied to hospital quality assessment and reimbursement. We sought to assess the use and impact of exclusion criteria associated with the CMS measure of door-to-balloon time in primary PCI. All primary PCI-eligible patients at 3 Massachusetts hospitals (Brigham and Women's, Massachusetts General, and North Shore Medical Center) were evaluated for CMS reporting status. Rates of CMS reporting exclusion were the primary end points of interest. Key secondary end points were between-group differences in patient characteristics, door-to-balloon times, and 1-year mortality rates. From 2005 to 2011, 26% (408) of the 1548 primary PCI cases were excluded from CMS reporting. This percentage increased over the study period from 13.9% in 2005 to 36.7% in the first 3 quarters of 2011 (P<0.001). The most frequent cause of exclusion was for a diagnostic dilemma such as a nondiagnostic initial ECG, accounting for 31.2% of excluded patients. Although 95% of CMS-reported cases met door-to-balloon time goals in 2011, this was true of only 61% of CMS-excluded cases and consequently 82.6% of all primary PCI cases performed that year. The 1-year mortality for CMS-excluded patients was double that of CMS-included patients (13.5% versus 6.6%; P<0.001). More than a quarter of patients who underwent primary PCI were excluded from hospital quality reports collected by CMS, and this percentage has grown substantially over time. These findings may have significant implications for our understanding of process improvement in primary PCI and mechanisms for reimbursement through Medicare.

Colistin Methanesulfonate Is an Inactive Prodrug of Colistin against Pseudomonas aeruginosa

PubMed Central

Bergen, Phillip J.; Li, Jian; Rayner, Craig R.; Nation, Roger L.

2006-01-01

There is a dearth of information on the pharmacodynamics of “colistin,” despite its increasing use as a last line of defense for treatment of infections caused by multidrug-resistant gram-negative organisms. The antimicrobial activities of colistin and colistin methanesulfonate (CMS) were investigated by studying the time-kill kinetics of each against a type culture of Pseudomonas aeruginosa in cation-adjusted Mueller-Hinton broth. The appearance of colistin from CMS spiked at 8.0 and 32 mg/liter was measured by high-performance liquid chromatography, which generated colistin concentration-time profiles. These concentration-time profiles were subsequently mimicked in other incubations, independent of CMS, by incrementally spiking colistin. When the cultures were spiked with CMS at either concentration, there was a substantial delay in the onset of the killing effect which was not evident until the concentrations of colistin generated from the hydrolysis of CMS had reached approximately 0.5 to 1 mg/liter (i.e., ∼0.5 to 1 times the MIC for colistin). The time course of the killing effect was similar when colistin was added incrementally to achieve the same colistin concentration-time course observed from the hydrolysis of CMS. Given that the killing kinetics of CMS can be accounted for by the appearance of colistin, CMS is an inactive prodrug of colistin with activity against P. aeruginosa. This is the first study to demonstrate the formation of colistin in microbiological media containing CMS and to demonstrate that CMS is an inactive prodrug of colistin. These findings have important implications for susceptibility testing involving “colistin,” in particular, for MIC measurement and for microbiological assays and pharmacokinetic and pharmacodynamic studies. PMID:16723551

The discovery and measurements of a Higgs boson.

PubMed

Gianotti, F; Virdee, T S

2015-01-13

In July 2012, the ATLAS and CMS collaborations at CERN's Large Hadron Collider announced the discovery of a Higgs-like boson, a new heavy particle at a mass more than 130 times the mass of a proton. Since then, further data have revealed its properties to be strikingly similar to those of the Standard Model Higgs boson, a particle expected from the mechanism introduced almost 50 years ago by six theoreticians including British physicists Peter Higgs from Edinburgh University and Tom Kibble from Imperial College London. The discovery is the culmination of a truly remarkable scientific journey and undoubtedly the most significant scientific discovery of the twenty-first century so far. Its experimental confirmation turned out to be a monumental task requiring the creation of an accelerator and experiments of unprecedented capability and complexity, designed to discern the signatures that correspond to the Higgs boson. Thousands of scientists and engineers, in each of the ATLAS and CMS teams, came together from all four corners of the world to make this massive discovery possible.

Advanced strategies for quality control of Chinese medicines.

PubMed

Zhao, Jing; Ma, Shuang-Cheng; Li, Shao-Ping

2018-01-05

Quality control is always the critical issue for Chinese medicines (CMs) with their worldwide increasing use. Different from western medicine, CMs are usually considered that multiple constituents are responsible for the therapeutic effects. Therefore, quality control of CMs is a challenge. In 2011, the strategies for quantification, related to the markers, reference compounds and approaches, in quality control of CMs were reviewed (Li, et al., J. Pharm. Biomed. Anal., 2011, 55, 802-809). Since then, some new strategies have been proposed in these fields. Therefore, the review on the strategies for quality control of CMs should be updated to improve the safety and efficacy of CMs. Herein, novel strategies related to quality marker discovery, reference compound development and advanced approaches (focused on glyco-analysis) for quality control, during 2011-2016, were summarized and discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Partial characterization of chayotextle starch-based films added with ascorbic acid encapsulated in resistant starch.

PubMed

Martínez-Ortiz, Miguel A; Vargas-Torres, Apolonio; Román-Gutiérrez, Alma D; Chavarría-Hernández, Norberto; Zamudio-Flores, Paul B; Meza-Nieto, Martín; Palma-Rodríguez, Heidi M

2017-05-01

Chayotextle starch was modified by subjecting it to a dual treatment with acid and heating-cooling cycles. This caused a decrease in the content of amylose, which showed values of 30.22%, 4.80%, 3.27% and 3.57% for native chayotextle starch (NCS), starch modified by acid hydrolysis (CMS), and CMS with one (CMS1AC) and three autoclave cycles (CMS3AC), respectively. The percentage of crystallinity showed an increase of 36.9%-62% for NCS and CMS3AC. The highest content of resistant starch (RS) was observed in CMS3AC (37.05%). The microcapsules were made with CMS3AC due to its higher RS content; the total content of ascorbic acid of the microcapsules was 82.3%. The addition of different concentrations of CMS3AC microcapsules (0%, 2.5%, 6.255% and 12.5%) to chayotextle starch-based films (CSF) increased their tensile strength and elastic modulus. The content of ascorbic acid and RS in CSF was ranged from 0% to 59.4% and from 4.84% to 37.05% in the control film and in the film mixed with CMS3AC microcapsules, respectively. Water vapor permeability (WVP) values decreased with increasing concentrations of microcapsules in the films. Microscopy observations showed that higher concentrations of microcapsules caused agglomerations due their poor distribution in the matrix of the films. Copyright © 2017 Elsevier B.V. All rights reserved.

Human cardiomyocyte generation from pluripotent stem cells: A state-of-art.

PubMed

Talkhabi, Mahmood; Aghdami, Nasser; Baharvand, Hossein

2016-01-15

The human heart is considered a non-regenerative organ. Worldwide, cardiovascular diseases continue to be the leading cause of death. Despite advances in cardiac treatment, myocardial repair remains severely limited by the lack of an appropriate source of viable cardiomyocytes (CMs) to replace damaged tissue. Human pluripotent stem cells (hPSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can efficiently be differentiated into functional CMs necessary for cell replacement therapy and other potential applications. The number of protocols that derive CMs from hPSCs has increased exponentially over the past decade following observation of the first human beating CMs. A number of highly efficient, chemical based protocols have been developed to generate human CMs (hCMs) in small-scale and large-scale suspension systems. To reduce the heterogeneity of hPSC-derived CMs, the differentiation protocols were modulated to exclusively generate atrial-, ventricular-, and nodal-like CM subtypes. Recently, remarkable advances have been achieved in hCM generation including chemical-based cardiac differentiation, cardiac subtype specification, large-scale suspension culture differentiation, and development of chemically defined culture conditions. These hCMs could be useful particularly in the context of in vitro disease modeling, pharmaceutical screening and in cellular replacement therapies once the safety issues are overcome. Herein we review recent progress in the in vitro generation of CMs and cardiac subtypes from hPSCs and discuss their potential applications and current limitations. Copyright © 2015 Elsevier Inc. All rights reserved.

Involvement of p38 MAPK- and JNK-modulated expression of Bcl-2 and Bax in Naja nigricollis CMS-9-induced apoptosis of human leukemia K562 cells.

PubMed

Chen, Ying-Jung; Liu, Wen-Hsin; Kao, Pei-Hsiu; Wang, Jeh-Jeng; Chang, Long-Sen

2010-06-15

CMS-9, a phospholipase A(2) (PLA(2)) isolated from Naja nigricollis venom, induced apoptosis of human leukemia K562 cells, characterized by mitochondrial depolarization, modulation of Bcl-2 family members, cytochrome c release and activation of caspases 9 and 3. Moreover, an increase in intracellular Ca2+ concentration and the production of reactive oxygen species (ROS) was noted. Pretreatment with BAPTA-AM (Ca2+ chelator) and N-acetylcysteine (NAC, ROS scavenger) proved that Ca2+ was an upstream event in inducing ROS generation. Upon exposure to CMS-9, activation of p38 MAPK and JNK was observed in K562 cells. BAPTA-AM or NAC abrogated CMS-9-elicited p38 MAPK and JNK activation, and rescued viability of CMS-9-treated K562 cells. SB202190 (p38 MAPK inhibitor) and SP600125 (JNK inhibitor) suppressed CMS-9-induced dissipation of mitochondrial membrane potential, Bcl-2 down-regulation, Bax up-regulation and increased mitochondrial translocation of Bax. Inactivation of PLA(2) activity reduced drastically the cytotoxicity of CMS-9, and a combination of lysophosphatidylcholine and stearic acid mimicked the cytotoxic effects of CMS-9. Taken together, our data suggest that CMS-9-induced apoptosis of K562 cells is catalytic activity-dependent and is mediated through mitochondria-mediated death pathway triggered by Ca2+/ROS-evoked p38 MAPK and JNK activation. 2010 Elsevier Ltd. All rights reserved.

Origin of the CMS gene locus in rapeseed cybrid mitochondria: active and inactive recombination produces the complex CMS gene region in the mitochondrial genomes of Brassicaceae.

PubMed

Oshima, Masao; Kikuchi, Rie; Imamura, Jun; Handa, Hirokazu

2010-01-01

CMS (cytoplasmic male sterile) rapeseed is produced by asymmetrical somatic cell fusion between the Brassica napus cv. Westar and the Raphanus sativus Kosena CMS line (Kosena radish). The CMS rapeseed contains a CMS gene, orf125, which is derived from Kosena radish. Our sequence analyses revealed that the orf125 region in CMS rapeseed originated from recombination between the orf125/orfB region and the nad1C/ccmFN1 region by way of a 63 bp repeat. A precise sequence comparison among the related sequences in CMS rapeseed, Kosena radish and normal rapeseed showed that the orf125 region in CMS rapeseed consisted of the Kosena orf125/orfB region and the rapeseed nad1C/ccmFN1 region, even though Kosena radish had both the orf125/orfB region and the nad1C/ccmFN1 region in its mitochondrial genome. We also identified three tandem repeat sequences in the regions surrounding orf125, including a 63 bp repeat, which were involved in several recombination events. Interestingly, differences in the recombination activity for each repeat sequence were observed, even though these sequences were located adjacent to each other in the mitochondrial genome. We report results indicating that recombination events within the mitochondrial genomes are regulated at the level of specific repeat sequences depending on the cellular environment.

Risk factors for cardiomyopathy syndrome (CMS) in Norwegian salmon farming.

PubMed

Bang Jensen, Britt; Brun, Edgar; Fineid, Birgitte; Larssen, Rolf Bjerke; Kristoffersen, Anja B

2013-12-12

Cardiomyopathy syndrome (CMS) has been an economically important disease in Norwegian aquaculture since the 1990s. In this study, data on monthly production characteristics and case registrations were combined in a cohort study and supplemented with a questionnaire-based case-control survey on management factors in order to identify risk factors for CMS. The cohort study included cases and controls from 2005 to 2012. From this dataset differences between all cases and controls were analyzed by a mixed effect multivariate logistic regression. From this we found that the probability of CMS increased with increasing time in the sea, infection pressure, and cohort size, and that cohorts which had previously been diagnosed with heart and skeletal muscle inflammation or which were in farms with a history of CMS in previous cohorts had double the odds of developing CMS. The model was then used to calculate the predicted value for each cohort from which additional data were obtained via the questionnaire-based survey and used as offset for calculating the probability of CMS in a semi-univariate analysis of additional risk factors. Finally, the model was used to calculate the probability of developing CMS in 100 different scenarios in which the cohorts were subject to increasingly worse conditions with regards to the risk factors from the dataset. We believe that this exercise is a good way of communicating the findings to farmers, so they can make informed decisions when trying to avoid CMS in their fish cohorts.

The CMS Journey to LHC Physics

ScienceCinema

Virdee, Tejinder

2018-04-27

An overview of the design, the construction and physics of CMS will be given. A history of construction, encompassing the R&D; and challenges faced over the last decade and a half, will be recalled using selected examples. CMS is currently in the final stages of installation and commissioning is gathering pace. After a short status report of where CMS stands today some of the expected (great) physics to come will be outlined.

The Development of Educational Environment Suited to the Japan-Specific Educational Service Using Requirements Engineering Techniques: Case Study of Running Sakai with PostgreSQL

ERIC Educational Resources Information Center

Terawaki, Yuki; Takahashi, Yuichi; Kodama, Yasushi; Yana, Kazuo

2011-01-01

This paper describes an integration of different Relational Database Management System (RDBMS) of two Course Management Systems (CMS) called Sakai and the Common Factory for Inspiration and Value in Education (CFIVE). First, when the service of CMS is provided campus-wide, the problems of user support, CMS operation and customization of CMS are…

Effect of vitamin E on reversibility of renal function following discontinuation of colistin in rats: Histological and biochemical investigations.

PubMed

Ghlissi, Zohra; Hakim, Ahmed; Mnif, Hela; Kallel, Rim; Zeghal, Khaled; Boudawara, Tahiya; Sahnoun, Zouheir

2018-01-01

This study was carried out to evaluate spontaneous renal regeneration after stopping colistin methanesulfonate (CMS), which induces tubular damage, and the curative effect of Vitamin E (vit E) in rats. Animals were given the following: sterile saline (n = 6), 300,000 IU/kg/ day of CMS (n = 24), or 450,000 IU/kg/day of CMS (n = 24) for seven days. Each CMS group was subdivided into four subgroups (n = 6) and sacrificed as follows: (i) 12 h after stopping CMS, (ii) two weeks after stopping CMS, (iii) two weeks after stopping treatment with vit E, and (iv) two weeks after stopping treatment with olive oil. Subsequently, plasma creatinine (pCr), urine N-acetyl-b-D-glucosaminidase (NAG), renal tissue level of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione reductase (GSH), and renal histology were tested. CMS-induced tubular damage increased the NAG and MDA levels and decreased the SOD and GSH activities. After two weeks of stopping CMS, there was no significant renal recovery. However, treatment with vit E improved tubular regeneration and reduced the biochemical impairments. Two weeks might not be long enough for significant spontaneous renal regeneration. Improvement of renal parameters by vit E could be explained by the reduction of oxidative stress damage.

Effect of tribulus terrestris saponins on behavior and neuroendocrine in chronic mild stress depression rats.

PubMed

Wang, Zhe; Zhang, Dongdong; Hui, Shan; Zhang, Yingjin; Hu, Suiyu

2013-04-01

To observe the effect of tribulus terrestris saponins (TTS) on behavior and neuroendocrine of chronic mild stress (CMS) depression rats. Thirty male Sprague-Dawley rats were randomly allocated to six groups: vehicle group, CMS group, CMS + fluoxetine group and CMS + TTS of low-dosage (0.375 g/kg), medium-dosage (0.75 g/kg) and high-dosage (2.25 g/kg) groups. All rats except the vehicle group singly housed and exposed an unpredicted sequence of mild stressors. The behavior of rats was detected by open-field test (OFT) and sucrose preference test (SPT). The concentration of corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH) in serum of the rats were detected by radioimmunoassay. The concentration of cortisol (CORT) in serum was detected by enzyme immunoassay. CMS procedure not only significantly decreased the scores of crossing, rears and grooming in OFT and the sucrose preference in SPT (all P < 0.01), but also markedly increased serum CRH and CORT levels (both P < 0.05). Treatment with TTS (0.75 and 2.25 g/kg) could significantly prevent all of these abnormalities induced by CMS (P < 0.05, P < 0.01). CMS can affect rat behavior and neuroendocrine and cause depression. TTS has the antagonism on CMS and produce antidepressive effects.

Congenital abnormalities in Japanese patients with Menkes disease.

PubMed

Gu, Yan-Hong; Kodama, Hiroko; Kato, Tadaaki

2012-10-01

Menkes disease (MNK) is an X-linked recessive disorder. Incidence of live-born infants with MNK is 2.8 per million live births in Japan. The aim of this study was to observe congenital malformations (CMs) in MNK patients. Subjects comprised 35 Japanese male patients with classical MNK who received copper histidine treatment. Patient clinical data were obtained anonymously from medical records or medical record summaries by pediatrician's retrospective review through a survey. We observed 21 different CMs in 14 patients. Eight of these had a single CM, while six had multiple CMs. The most frequent CM was higher arched palate with other CMs found in five patients. There was no relationship between CMs and mutations in the ATP7A gene. Using Mann-Whitney U tests, age at death was also significantly lower in MNK patients with CMs (P<0.05), compared to those without CMs, even though there was no significant difference of age onset, age at diagnosis and age at start of treatment with copper histidine between both groups of patients. Sudden death occurred in three MNK patients with CMs only: two with congenital heart disease, and one with microphallus. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

SiteDB: Marshalling people and resources available to CMS

NASA Astrophysics Data System (ADS)

Metson, S.; Bonacorsi, D.; Dias Ferreira, M.; Egeland, R.

2010-04-01

In a collaboration the size of CMS (approx. 3000 users, and almost 100 computing centres of varying size) communication and accurate information about the sites it has access to is vital in co-ordinating the multitude of computing tasks required for smooth running. SiteDB is a tool developed by CMS to track sites available to the collaboration, the allocation to CMS of resources available at those sites and the associations between CMS members and the sites (as either a manager/operator of the site or a member of a group associated to the site). It is used to track the roles a person has for an associated site or group. SiteDB eases the coordination load for the operations teams by providing a consistent interface to manage communication with the people working at a site, by identifying who is responsible for a given task or service at a site and by offering a uniform interface to information on CMS contacts and sites. SiteDB provides api's and reports for other CMS tools to use to access the information it contains, for instance enabling CRAB to use "user friendly" names when black/white listing CE's, providing role based authentication and authorisation for other web based services and populating various troubleshooting squads in external ticketing systems in use daily by CMS Computing operations.

Congenital Myasthenic Syndromes or Inherited Disorders of Neuromuscular Transmission: Recent Discoveries and Open Questions

PubMed Central

Nicole, Sophie; Azuma, Yoshiteru; Bauché, Stéphanie; Eymard, Bruno; Lochmüller, Hanns; Slater, Clarke

2017-01-01

Congenital myasthenic syndromes (CMS) form a heterogeneous group of rare diseases characterized by fatigable muscle weakness. They are genetically-inherited and caused by defective synaptic transmission at the cholinergic neuromuscular junction (NMJ). The number of genes known to cause CMS when mutated is currently 30, and the relationship between fatigable muscle weakness and defective functions is quite well-understood for many of them. However, some of the most recent discoveries in individuals with CMS challenge our knowledge of the NMJ, where the basis of the pathology has mostly been investigated in animal models. Frontier forms between CMS and congenital myopathy, which have been genetically and clinically identified, underline the poorly understood interplay between the synaptic and extrasynaptic molecules in the neuromuscular system. In addition, precise electrophysiological and histopathological investigations of individuals with CMS suggest an important role of NMJ plasticity in the response to CMS pathogenesis. While efficient drug-based treatments are already available to improve neuromuscular transmission for most forms of CMS, others, as well as neurological and muscular comorbidities, remain resistant. Taken together, the available pathological data point to physiological issues which remain to be understood in order to achieve precision medicine with efficient therapeutics for all individuals suffering from CMS. PMID:29125502

Strengthening the resiliency of the coastal transportation system through integrated simulation of storm surge, inundation, and non-recurrent congestion in Northeast Florida.

DOT National Transportation Integrated Search

2013-05-01

In this study, the MTEVA (Developed as part of CMS #2009-010) has been advanced to apply storm surge and evacuation models to the greater Jacksonville area of Northeast Florida. Heuristic and time dynamic algorithms have been enhanced to work with th...

42 CFR 422.312 - Announcement of annual capitation rate, benchmarks, and methodology changes.

Code of Federal Regulations, 2013 CFR

2013-10-01

... than the first Monday in April each year, CMS announces to MA organizations and other interested parties the following information for each MA payment area for the following calendar year: (i) The annual MA capitation rate. (ii) The risk and other factors to be used in adjusting those rates under § 422...

42 CFR 422.312 - Announcement of annual capitation rate, benchmarks, and methodology changes.

Code of Federal Regulations, 2012 CFR

2012-10-01

... than the first Monday in April each year, CMS announces to MA organizations and other interested parties the following information for each MA payment area for the following calendar year: (i) The annual MA capitation rate. (ii) The risk and other factors to be used in adjusting those rates under § 422...

76 FR 33306 - Medicare Program; Pioneer Accountable Care Organization Model, Request for Applications; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-08

... information posted on our Center for Medicare and Medicaid Innovation (CMMI) Web site and in the Pioneer ACO Application. (For more information see http://innovations.cms.gov/areas-of-focus/seamless-and-coordinated-care... postmarked on or before July 18, 2011.'' Authority: Section 1115A of the Social Security Act. Dated: June 2...

42 CFR 412.424 - Methodology for calculating the Federal per diem payment amount.

Code of Federal Regulations, 2014 CFR

2014-10-01

... facilities located in a rural area as defined in § 412.402. (iii) Teaching adjustment. CMS adjusts the Federal per diem base rate by a factor to account for indirect teaching costs. (A) An inpatient psychiatric facility's teaching adjustment is based on the ratio of the number of full-time equivalent...

42 CFR 412.424 - Methodology for calculating the Federal per diem payment amount.

Code of Federal Regulations, 2013 CFR

2013-10-01

... facilities located in a rural area as defined in § 412.402. (iii) Teaching adjustment. CMS adjusts the Federal per diem base rate by a factor to account for indirect teaching costs. (A) An inpatient psychiatric facility's teaching adjustment is based on the ratio of the number of full-time equivalent...

42 CFR 412.424 - Methodology for calculating the Federal per diem payment amount.

Code of Federal Regulations, 2011 CFR

2011-10-01

... facilities located in a rural area as defined in § 412.402. (iii) Teaching adjustment. CMS adjusts the Federal per diem base rate by a factor to account for indirect teaching costs. (A) An inpatient psychiatric facility's teaching adjustment is based on the ratio of the number of full-time equivalent...

42 CFR 412.424 - Methodology for calculating the Federal per diem payment amount.

Code of Federal Regulations, 2010 CFR

2010-10-01

... facilities located in a rural area as defined in § 412.402. (iii) Teaching adjustment. CMS adjusts the Federal per diem base rate by a factor to account for indirect teaching costs. (A) An inpatient psychiatric facility's teaching adjustment is based on the ratio of the number of full-time equivalent...

42 CFR 412.424 - Methodology for calculating the Federal per diem payment amount.

Code of Federal Regulations, 2012 CFR

2012-10-01

... facilities located in a rural area as defined in § 412.402. (iii) Teaching adjustment. CMS adjusts the Federal per diem base rate by a factor to account for indirect teaching costs. (A) An inpatient psychiatric facility's teaching adjustment is based on the ratio of the number of full-time equivalent...

42 CFR 425.602 - Establishing the benchmark.

Code of Federal Regulations, 2014 CFR

2014-10-01

... claims. (5)(i) Using CMS Office of the Actuary national Medicare expenditure data for each of the years...-service program using data from CMS' Office of the Actuary. (2) To update the benchmark, CMS makes...

42 CFR 425.602 - Establishing the benchmark.

Code of Federal Regulations, 2012 CFR

2012-10-01

... claims. (5)(i) Using CMS Office of the Actuary national Medicare expenditure data for each of the years...-service program using data from CMS' Office of the Actuary. (2) To update the benchmark, CMS makes...

42 CFR 425.602 - Establishing the benchmark.

Code of Federal Regulations, 2013 CFR

2013-10-01

... claims. (5)(i) Using CMS Office of the Actuary national Medicare expenditure data for each of the years...-service program using data from CMS' Office of the Actuary. (2) To update the benchmark, CMS makes...

45 CFR 150.345 - Appeal of proposed penalty.

Code of Federal Regulations, 2010 CFR

2010-10-01

... CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement With Respect to Issuers and... against which CMS has assessed a penalty may appeal that penalty in accordance with § 150.401 et seq. ...

Evaluation of efficacy of natural astaxanthin and vitamin E in prevention of colistin-induced nephrotoxicity in the rat model.

PubMed

Ghlissi, Zohra; Hakim, Ahmed; Sila, Assaad; Mnif, Hela; Zeghal, Khaled; Rebai, Tarek; Bougatef, Ali; Sahnoun, Zouheir

2014-05-01

We evaluated the effect of astaxanthin (ASX) and vitamin E (vit E) on colistin methanesulfonate (CMS) induced-nephrotoxicity in rats. Animals were treated with sterile saline, 300000 or 450 000 IU/kg/day of CMS, CMS + ASX (20 mg/kg), CMS + vit E (100 mg/kg), or CMS + 1 ml/kg olive oil (OO) for 7 days. The plasma/urine creatinine (Cr) level, urine γ-glutamyl-transferase (GGT) level, and renal tissue activities in malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reductase (GSH), as well as renal histology were performed. CMS induced a tubular damage, increased the GGT and MDA levels, and decreased the activities of SOD, CAT, GPx and GSH. Co-treatment with ASX or vit E restored all biochemical parameters cited above and improved the histopathological damage. Nephrotoxicity induced by CMS might be due to oxidative damage. The improvement by ASX or vit E seems to be related to their antioxidant properties. Copyright © 2014 Elsevier B.V. All rights reserved.

Baicalin maintains late-stage functional cardiomyocytes in embryoid bodies derived from murine embryonic stem cells.

PubMed

Tang, Meilin; Yin, Mengmeng; Tang, Ming; Liang, Huamin; Yu, Chong; Hu, Xinwu; Luo, Hongyan; Baudis, Birte; Haustein, Moritz; Khalil, Markus; Sarić, Tomo; Hescheler, Jürgen; Xi, Jiaoya

2013-01-01

Low efficiency of cardiomyocyte (CM) differentiation from embryonic stem (ES) cells limits their therapeutic use. The objective of this study was to investigate the effect of baicalin, a natural flavonoid compound, on the in vitro cardiac differentiation of murine ES cells. The induction of ES cells into cardiac-like cells was performed by embryoid body (EB)-based differentiation method. The electrophysiological properties of the ES cell-derived CMs (ES-CMs) were measured by patch-clamp. The biomarkers of ES-CMs were determined by quantitative RT-PCR and immunofluorescence. Continuous baicalin treatment decreased the size of EBs, and increased the proportion of α-actinin-positive CMs and transcript level of cardiac specific markers in beating EBs by inducing cell death of non-CMs. Baicalin increased the percentage of working ES-CMs which had typical responses to β-adrenergic and muscarinic stimulations. Baicalin maintains the late-stage functional CMs in EBs derived from murine ES cells. This study describes a new insight into the various biological effects of baicalin on cardiac differentiation of pluripotent stem cells. Copyright © 2013 S. Karger AG, Basel.

The CMS dataset bookkeeping service

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

Afaq, Anzar,; /Fermilab; Dolgert, Andrew

2007-10-01

The CMS Dataset Bookkeeping Service (DBS) has been developed to catalog all CMS event data from Monte Carlo and Detector sources. It provides the ability to identify MC or trigger source, track data provenance, construct datasets for analysis, and discover interesting data. CMS requires processing and analysis activities at various service levels and the DBS system provides support for localized processing or private analysis, as well as global access for CMS users at large. Catalog entries can be moved among the various service levels with a simple set of migration tools, thus forming a loose federation of databases. DBS ismore » available to CMS users via a Python API, Command Line, and a Discovery web page interfaces. The system is built as a multi-tier web application with Java servlets running under Tomcat, with connections via JDBC to Oracle or MySQL database backends. Clients connect to the service through HTTP or HTTPS with authentication provided by GRID certificates and authorization through VOMS. DBS is an integral part of the overall CMS Data Management and Workflow Management systems.« less

Open access to high-level data and analysis tools in the CMS experiment at the LHC

DOE PAGES

Calderon, A.; Colling, D.; Huffman, A.; ...

2015-12-23

The CMS experiment, in recognition of its commitment to data preservation and open access as well as to education and outreach, has made its first public release of high-level data under the CC0 waiver: up to half of the proton-proton collision data (by volume) at 7 TeV from 2010 in CMS Analysis Object Data format. CMS has prepared, in collaboration with CERN and the other LHC experiments, an open-data web portal based on Invenio. The portal provides access to CMS public data as well as to analysis tools and documentation for the public. The tools include an event display andmore » histogram application that run in the browser. In addition a virtual machine containing a CMS software environment along with XRootD access to the data is available. Within the virtual machine the public can analyse CMS data, example code is provided. As a result, we describe the accompanying tools and documentation and discuss the first experiences of data use.« less

Starch-based nanocapsules fabricated through layer-by-layer assembly for oral delivery of protein to lower gastrointestinal tract.

PubMed

Zhang, Yiping; Chi, Chengdeng; Huang, Xiaoyi; Zou, Qin; Li, Xiaoxi; Chen, Ling

2017-09-01

Anionic carboxymethyl starch (CMS) and cationic quaternary ammonium starch (QAS), were used to fabricate nanocapsules through electrostatic layer by layer (LbL) alternate deposition onto colloidal BSA particles. An ideal starch-based colloidal nanocapsule was achieved by adjusting the degree of substitution (DS) and weight average molecular molar mass (M w ) of CMS. The nanocapsules fabricated by CMS with lower DS or M w possessed more compact and stable core-shell structure, which favoured the BSA delivery from the upper gastrointestinal tract (GIT) to the colon. In particular, CMS/QAS nanocapsules constructed by CMS with lower DS and M w showed better colon-specific delivery and release performance in simulated GIT fluid after 7days' storage in different kinds of beverage (33.04%-46.35% in upper GIT, 52.70%-64.97% in colon, respectively). These findings demonstrated that CMS/QAS nanocapsules constructed by CMS with lower DS and M w can be further exploited as a potential oral delivery system for protein to colon. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacokinetics of colistin and colistimethate sodium after a single 80-mg intravenous dose of CMS in young healthy volunteers.

PubMed

Couet, W; Grégoire, N; Gobin, P; Saulnier, P J; Frasca, D; Marchand, S; Mimoz, O

2011-06-01

Colistin pharmacokinetics (PK) was investigated in young healthy volunteers after a 1-h infusion of 80 mg (1 million international units (MIU)) of the prodrug colistin methanesulfonate (CMS). Concentration levels of CMS and colistin were determined in plasma and urine using a new chromatographic assay and analyzed simultaneously with a population approach after correcting the urine-related data for postexcretion hydrolysis of CMS into colistin. CMS and colistin have low volumes of distribution (14.0 and 12.4 liters, respectively), consistent with distribution being restricted to extracellular fluid. CMS is mainly excreted unchanged in urine (70% on average), with a typical renal clearance estimated at 103 ml/min-close to the glomerular filtration rate. Colistin elimination is essentially extrarenal, given that its renal clearance is 1.9 ml/min, consistent with extensive reabsorption. Colistin elimination is not limited by the formation rate because its half-life (3 h) is longer than that of CMS. The values of these pharmacokinetic parameters will serve as reference points for future comparisons with patients' data.

Exploiting analytics techniques in CMS computing monitoring

NASA Astrophysics Data System (ADS)

Bonacorsi, D.; Kuznetsov, V.; Magini, N.; Repečka, A.; Vaandering, E.

2017-10-01

The CMS experiment has collected an enormous volume of metadata about its computing operations in its monitoring systems, describing its experience in operating all of the CMS workflows on all of the Worldwide LHC Computing Grid Tiers. Data mining efforts into all these information have rarely been done, but are of crucial importance for a better understanding of how CMS did successful operations, and to reach an adequate and adaptive modelling of the CMS operations, in order to allow detailed optimizations and eventually a prediction of system behaviours. These data are now streamed into the CERN Hadoop data cluster for further analysis. Specific sets of information (e.g. data on how many replicas of datasets CMS wrote on disks at WLCG Tiers, data on which datasets were primarily requested for analysis, etc) were collected on Hadoop and processed with MapReduce applications profiting of the parallelization on the Hadoop cluster. We present the implementation of new monitoring applications on Hadoop, and discuss the new possibilities in CMS computing monitoring introduced with the ability to quickly process big data sets from mulltiple sources, looking forward to a predictive modeling of the system.

A novel application of Fiber Bragg Grating (FBG) sensors in MPGD

NASA Astrophysics Data System (ADS)

Abbaneo, D.; Abbas, M.; Abbrescia, M.; Abi Akl, M.; Aboamer, O.; Acosta, D.; Ahmad, A.; Ahmed, W.; Aleksandrov, A.; Altieri, P.; Asawatangtrakuldee, C.; Aspell, P.; Assran, Y.; Awan, I.; Bally, S.; Ban, Y.; Banerjee, S.; Barashko, V.; Barria, P.; Bencze, G.; Beni, N.; Benussi, L.; Bhopatkar, V.; Bianco, S.; Bos, J.; Bouhali, O.; Braghieri, A.; Braibant, S.; Buontempo, S.; Calabria, C.; Caponero, M.; Caputo, C.; Cassese, F.; Castaneda, A.; Cauwenbergh, S.; Cavallo, F. R.; Celik, A.; Choi, M.; Choi, S.; Christiansen, J.; Cimmino, A.; Colafranceschi, S.; Colaleo, A.; Conde Garcia, A.; Czellar, S.; Dabrowski, M. M.; De Lentdecker, G.; De Oliveira, R.; de Robertis, G.; Dildick, S.; Dorney, B.; Endroczi, G.; Errico, F.; Fenyvesi, A.; Ferrini, M.; Ferry, S.; Furic, I.; Giacomelli, P.; Gilmore, J.; Golovtsov, V.; Guiducci, L.; Guilloux, F.; Gutierrez, A.; Hadjiiska, R. M.; Hauser, J.; Hoepfner, K.; Hohlmann, M.; Hoorani, H.; Iaydjiev, P.; Jeng, Y. G.; Kamon, T.; Karchin, P.; Korytov, A.; Krutelyov, S.; Kumar, A.; Kim, H.; Lalli, A.; Lee, J.; Lenzi, T.; Litov, L.; Loddo, F.; Madorsky, A.; Maerschalk, T.; Maggi, M.; Magnani, A.; Mal, P. K.; Mandal, K.; Marchioro, A.; Marinov, A.; Majumdar, N.; Merlin, J. A.; Mitselmakher, G.; Mohanty, A. K.; Mohapatra, A.; Molnar, J.; Muhammad, S.; Mukhopadhyay, S.; Naimuddin, M.; Nuzzo, S.; Oliveri, E.; Pant, L. M.; Paolucci, P.; Park, I.; Passamonti, L.; Passeggio, G.; Pavlov, B.; Philipps, B.; Piccolo, D.; Pierluigi, D.; Postema, H.; Primavera, F.; Puig Baranac, A.; Radi, A.; Radogna, R.; Raffone, G.; Ranieri, A.; Rashevski, G.; Riccardi, C.; Rodozov, M.; Rodrigues, A.; Ropelewski, L.; RoyChowdhury, S.; Russo, A.; Ryu, G.; Ryu, M. S.; Safonov, A.; Salva, S.; Saviano, G.; Sharma, A.; Sharma, A.; Sharma, R.; Shah, A. H.; Shopova, M.; Sturdy, J.; Sultanov, G.; Swain, S. K.; Szillasi, Z.; Talvitie, J.; Tatarinov, A.; Tuuva, T.; Tytgat, M.; Valente, M.; Vai, I.; Van Stenis, M.; Venditti, R.; Verhagen, E.; Verwilligen, P.; Vitulo, P.; Volkov, S.; Vorobyev, A.; Wang, D.; Wang, M.; Yang, U.; Yang, Y.; Yonamine, R.; Zaganidis, N.; Zenoni, F.; Zhang, A.

2018-02-01

We present a novel application of Fiber Bragg Grating (FBG) sensors in the construction and characterisation of Micro Pattern Gaseous Detector (MPGD), with particular attention to the realisation of the largest triple (Gas electron Multiplier) GEM chambers so far operated, the GE1/1 chambers of the CMS experiment at LHC. The GE1/1 CMS project consists of 144 GEM chambers of about 0.5 m2 active area each, employing three GEM foils per chamber, to be installed in the forward region of the CMS endcap during the long shutdown of LHC in 2108-2019. The large active area of each GE1/1 chamber consists of GEM foils that are mechanically stretched in order to secure their flatness and the consequent uniform performance of the GE1/1 chamber across its whole active surface. So far FBGs have been used in high energy physics mainly as high precision positioning and re-positioning sensors and as low cost, easy to mount, low space consuming temperature sensors. FBGs are also commonly used for very precise strain measurements in material studies. In this work we present a novel use of FBGs as flatness and mechanical tensioning sensors applied to the wide GEM foils of the GE1/1 chambers. A network of FBG sensors have been used to determine the optimal mechanical tension applied and to characterise the mechanical tension that should be applied to the foils. We discuss the results of the test done on a full-sized GE1/1 final prototype, the studies done to fully characterise the GEM material, how this information was used to define a standard assembly procedure and possible future developments.

Mutations in GFPT1-related congenital myasthenic syndromes are associated with synaptic morphological defects and underlie a tubular aggregate myopathy with synaptopathy.

PubMed

Bauché, Stéphanie; Vellieux, Geoffroy; Sternberg, Damien; Fontenille, Marie-Joséphine; De Bruyckere, Elodie; Davoine, Claire-Sophie; Brochier, Guy; Messéant, Julien; Wolf, Lucie; Fardeau, Michel; Lacène, Emmanuelle; Romero, Norma; Koenig, Jeanine; Fournier, Emmanuel; Hantaï, Daniel; Streichenberger, Nathalie; Manel, Veronique; Lacour, Arnaud; Nadaj-Pakleza, Aleksandra; Sukno, Sylvie; Bouhour, Françoise; Laforêt, Pascal; Fontaine, Bertrand; Strochlic, Laure; Eymard, Bruno; Chevessier, Frédéric; Stojkovic, Tanya; Nicole, Sophie

2017-08-01

Mutations in GFPT1 (glutamine-fructose-6-phosphate transaminase 1), a gene encoding an enzyme involved in glycosylation of ubiquitous proteins, cause a limb-girdle congenital myasthenic syndrome (LG-CMS) with tubular aggregates (TAs) characterized predominantly by affection of the proximal skeletal muscles and presence of highly organized and remodeled sarcoplasmic tubules in patients' muscle biopsies. We report here the first long-term clinical follow-up of 11 French individuals suffering from LG-CMS with TAs due to GFPT1 mutations, of which nine are new. Our retrospective clinical evaluation stresses an evolution toward a myopathic weakness that occurs concomitantly to ineffectiveness of usual CMS treatments. Analysis of neuromuscular biopsies from three unrelated individuals demonstrates that the maintenance of neuromuscular junctions (NMJs) is dramatically impaired with loss of post-synaptic junctional folds and evidence of denervation-reinnervation processes affecting the three main NMJ components. Moreover, molecular analyses of the human muscle biopsies confirm glycosylation defects of proteins with reduced O-glycosylation and show reduced sialylation of transmembrane proteins in extra-junctional area. Altogether, these results pave the way for understanding the etiology of this rare neuromuscular disorder that may be considered as a "tubular aggregates myopathy with synaptopathy".

Risk factors for development of postoperative cerebellar mutism syndrome in children after medulloblastoma surgery.

PubMed

Pols, San Y C V; van Veelen, Marie Lise C; Aarsen, Femke K; Gonzalez Candel, Antonia; Catsman-Berrevoets, Coriene E

2017-07-01

OBJECTIVE Postoperative cerebellar mutism syndrome (pCMS) occurs in 7%-50% of children after cerebellar tumor surgery. Typical features include a latent onset of 1-2 days after surgery, transient mutism, emotional lability, and a wide variety of motor and neurobehavioral abnormalities. Sequelae of this syndrome usually persist long term. The principal causal factor is bilateral surgical damage (regardless of tumor location) to any component of the proximal efferent cerebellar pathway, which leads to temporary dysfunction of cerebral cortical regions as a result of diaschisis. Tumor type, cerebellar midline location, and brainstem involvement are risk factors for pCMS that have been identified repeatedly, but they do not explain its latent onset. Ambiguous or negative results for other factors, such as hydrocephalus, postoperative meningitis, length of vermian incision, and tumor size, have been reached. The aim of this study was to identify perioperative clinical, radiological, and laboratory factors that also increase risk for the development of pCMS. The focus was on factors that might explain the delayed onset of pCMS and thus might provide a time window for taking precautionary measures to prevent pCMS or reduce its severity. The study was focused specifically on children who had undergone surgery for medulloblastoma. METHODS In this single-center retrospective cohort study, the authors included 71 children with medulloblastoma, 28 of whom developed pCMS after primary resection. Clinical and laboratory data were collected prospectively and analyzed systematically. Variables were included for univariate and multivariate analysis. RESULTS Univariate regression analysis revealed 7 variables that had a significant influence on pCMS onset, namely, tumor size, maximum tumor diameter > 5 cm, tumor infiltration or compression of the brainstem, significantly larger decreases in hemoglobin (p = 0.010) and hematocrit (p = 0.003) in the pCMS group after surgery than in the no-pCMS group, significantly more reported incidents of severe bleeding in the tumor bed during surgery in the pCMS group, preoperative hydrocephalus, and a mean body temperature rise of 0.5°C in the first 4 days after surgery in the pCMS group. Multiple regression analysis revealed that tumor size, tumor infiltration into or compression of the brainstem, and higher mean body temperature in the first 4 postoperative days were independent and highly significant predictors for pCMS. CONCLUSIONS The authors confirmed earlier findings that tumor-associated preoperative conditions, such as a maximum tumor diameter ≥ 5 cm and infiltration into or compression of the brainstem, are associated with a higher risk for the development of pCMS. Most importantly, the authors found that a 0.5°C higher mean body temperature in the first 4 postoperative days increased the odds ratio for the development of pCMS almost 5-fold. These data suggest that an important focus for the prevention of pCMS in children who have undergone medulloblastoma surgery might be rigorous maintenance of normothermia as standard care after surgery.

The Consensus Molecular Subtypes of Colorectal Cancer

PubMed Central

Guinney, Justin; Dienstmann, Rodrigo; Wang, Xin; de Reyniès, Aurélien; Schlicker, Andreas; Soneson, Charlotte; Marisa, Laetitia; Roepman, Paul; Nyamundanda, Gift; Angelino, Paolo; Bot, Brian M.; Morris, Jeffrey S.; Simon, Iris M.; Gerster, Sarah; Fessler, Evelyn; de Sousa e Melo, Felipe; Missiaglia, Edoardo; Ramay, Hena; Barras, David; Homicsko, Krisztian; Maru, Dipen; Manyam, Ganiraju C.; Broom, Bradley; Boige, Valerie; Perez-Villamil, Beatriz; Laderas, Ted; Salazar, Ramon; Gray, Joe W.; Hanahan, Douglas; Tabernero, Josep; Bernards, Rene; Friend, Stephen H.; Laurent-Puig, Pierre; Medema, Jan Paul; Sadanandam, Anguraj; Wessels, Lodewyk; Delorenzi, Mauro; Kopetz, Scott; Vermeulen, Louis; Tejpar, Sabine

2015-01-01

Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression–based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMS) with distinguishing features: CMS1 (MSI Immune, 14%), hypermutated, microsatellite unstable, strong immune activation; CMS2 (Canonical, 37%), epithelial, chromosomally unstable, marked WNT and MYC signaling activation; CMS3 (Metabolic, 13%), epithelial, evident metabolic dysregulation; and CMS4 (Mesenchymal, 23%), prominent transforming growth factor β activation, stromal invasion, and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intra-tumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC – with clear biological interpretability – and the basis for future clinical stratification and subtype–based targeted interventions. PMID:26457759

Care management service and falls prevention: a case-control study in a Chinese population.

PubMed

Leung, Angela Y M; Lou, Vivian W Q; Chan, Kin Sun; Yung, Alison; Chi, Iris

2010-04-01

This study evaluates the effect of a care management service (CMS) on falls in older adults. This is a retrospective case-control study with 78 CMS recipients as the case group who received CMS and another 312 community-dwelling frail elders as the control group.The groups were matched by age, gender, activity of daily living, cognitive impairment, and unsteady gait. Thus they were comparable in characteristics and frailty. Among the 390 participants, 89 older adults (23.0%) had falls in the 90 days prior to the survey. After controlling for the identified risk factors for falls, the odds ratio of CMS was 0.27 (95% confidence interval = 0.110-0.663, p < .01). These findings indicate that CMS recipients have a lower chance for falls compared to their counterparts. The two features of CMS (comprehensive assessment and multidisciplinary actions to reduce fall risks) are discussed.

Selective depression of titanaugite in the ilmenite flotation with carboxymethyl starch

NASA Astrophysics Data System (ADS)

Meng, Qingyou; Yuan, Zhitao; Yu, Li; Xu, Yuankai; Du, Yusheng; Zhang, Chen

2018-05-01

In order to intensify the flotation separation of ilmenite from titanaugite, surface modification of mineral particles was carried out using carboxymethyl starch (CMS) by microflotation experiments, zeta potential measurements, Fourier transform infrared (FTIR) and atomic force microscopy (AFM) analysis. Microflotation results showed that CMS was a selective depressant, and it effectively enhanced the floatability difference between ilmenite and titanaugite in the pH range from 6.0 to 10.0. As it was revealed by the zeta potential, FTIR and AFM analysis, the CMS adsorption occurred onto mineral surfaces through chemisorption and hydrogen bonding, while CMS exhibited a stronger interaction with titanaugite than ilmenite. After that, the CMS adsorption impeded the adsorption of sodium oleate collector on titanaugite surfaces, giving rise to a concomitant decrease in the floatability of titanaugite. These findings exhibit great potential for CMS application in the selective flotation of ilmenite.

Cross-layer cluster-based energy-efficient protocol for wireless sensor networks.

PubMed

Mammu, Aboobeker Sidhik Koyamparambil; Hernandez-Jayo, Unai; Sainz, Nekane; de la Iglesia, Idoia

2015-04-09

Recent developments in electronics and wireless communications have enabled the improvement of low-power and low-cost wireless sensors networks (WSNs). One of the most important challenges in WSNs is to increase the network lifetime due to the limited energy capacity of the network nodes. Another major challenge in WSNs is the hot spots that emerge as locations under heavy traffic load. Nodes in such areas quickly drain energy resources, leading to disconnection in network services. In such an environment, cross-layer cluster-based energy-efficient algorithms (CCBE) can prolong the network lifetime and energy efficiency. CCBE is based on clustering the nodes to different hexagonal structures. A hexagonal cluster consists of cluster members (CMs) and a cluster head (CH). The CHs are selected from the CMs based on nodes near the optimal CH distance and the residual energy of the nodes. Additionally, the optimal CH distance that links to optimal energy consumption is derived. To balance the energy consumption and the traffic load in the network, the CHs are rotated among all CMs. In WSNs, energy is mostly consumed during transmission and reception. Transmission collisions can further decrease the energy efficiency. These collisions can be avoided by using a contention-free protocol during the transmission period. Additionally, the CH allocates slots to the CMs based on their residual energy to increase sleep time. Furthermore, the energy consumption of CH can be further reduced by data aggregation. In this paper, we propose a data aggregation level based on the residual energy of CH and a cost-aware decision scheme for the fusion of data. Performance results show that the CCBE scheme performs better in terms of network lifetime, energy consumption and throughput compared to low-energy adaptive clustering hierarchy (LEACH) and hybrid energy-efficient distributed clustering (HEED).

Maximum Peak Systolic Velocity and Management of Highly Vascularized Retained Products of Conception.

PubMed

Van den Bosch, Thierry; Van Schoubroeck, Dominique; Timmerman, Dirk

2015-09-01

The purpose of this study was to evaluate blood loss and procedure-related complications during and after surgical removal of retained products of conception with high-velocity enhanced myometrial vascularity. We conducted a prospective study of 18 consecutive women with a diagnosis of retained products of conception and enhanced myometrial vascularity, with a peak systolic velocity (PSV) higher than 60 cm/s. All underwent ultrasound-guided surgical removal of the retained products under general anesthesia. Blood loss during the procedure was collected and recorded. The removed tissue was sent for histologic examination. An ultrasound examination was repeated within 24 hours. Five patients had retained products of conception after a term delivery, 1 after a second-trimester termination of pregnancy, 7 after a spontaneous first-trimester miscarriage, and 5 after a first-trimester termination elsewhere. The PSV in the area of enhanced myometrial vascularity at diagnosis ranged from 61.0 to 152.6 cm/s (mean, 104.9 cm/s). The estimated blood loss at surgery ranged from 20 to 1000 mL (mean, 200 mL). After surgery, the PSV in the myometrium dropped dramatically (≤30 cm/s in all but 1 case). In all cases, trophoblastic tissue was confirmed at histologic examination. Although surgical removal of retained products of conception was uneventful in most cases, heavy bleeding has to be anticipated in cases of high-velocity flow in the myometrium underlying residual trophoblastic tissue. Accordingly, in cases of high-velocity enhanced myometrial vascularity, we advocate surgical removal of the residual tissue under ultrasound guidance by an experienced surgeon and in the presence of a fully informed anesthetist. © 2015 by the American Institute of Ultrasound in Medicine.

Monitoring data transfer latency in CMS computing operations

DOE PAGES

Bonacorsi, Daniele; Diotalevi, Tommaso; Magini, Nicolo; ...

2015-12-23

During the first LHC run, the CMS experiment collected tens of Petabytes of collision and simulated data, which need to be distributed among dozens of computing centres with low latency in order to make efficient use of the resources. While the desired level of throughput has been successfully achieved, it is still common to observe transfer workflows that cannot reach full completion in a timely manner due to a small fraction of stuck files which require operator intervention.For this reason, in 2012 the CMS transfer management system, PhEDEx, was instrumented with a monitoring system to measure file transfer latencies, andmore » to predict the completion time for the transfer of a data set. The operators can detect abnormal patterns in transfer latencies while the transfer is still in progress, and monitor the long-term performance of the transfer infrastructure to plan the data placement strategy.Based on the data collected for one year with the latency monitoring system, we present a study on the different factors that contribute to transfer completion time. As case studies, we analyze several typical CMS transfer workflows, such as distribution of collision event data from CERN or upload of simulated event data from the Tier-2 centres to the archival Tier-1 centres. For each workflow, we present the typical patterns of transfer latencies that have been identified with the latency monitor.We identify the areas in PhEDEx where a development effort can reduce the latency, and we show how we are able to detect stuck transfers which need operator intervention. Lastly, we propose a set of metrics to alert about stuck subscriptions and prompt for manual intervention, with the aim of improving transfer completion times.« less

Monitoring data transfer latency in CMS computing operations

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

Bonacorsi, Daniele; Diotalevi, Tommaso; Magini, Nicolo

During the first LHC run, the CMS experiment collected tens of Petabytes of collision and simulated data, which need to be distributed among dozens of computing centres with low latency in order to make efficient use of the resources. While the desired level of throughput has been successfully achieved, it is still common to observe transfer workflows that cannot reach full completion in a timely manner due to a small fraction of stuck files which require operator intervention.For this reason, in 2012 the CMS transfer management system, PhEDEx, was instrumented with a monitoring system to measure file transfer latencies, andmore » to predict the completion time for the transfer of a data set. The operators can detect abnormal patterns in transfer latencies while the transfer is still in progress, and monitor the long-term performance of the transfer infrastructure to plan the data placement strategy.Based on the data collected for one year with the latency monitoring system, we present a study on the different factors that contribute to transfer completion time. As case studies, we analyze several typical CMS transfer workflows, such as distribution of collision event data from CERN or upload of simulated event data from the Tier-2 centres to the archival Tier-1 centres. For each workflow, we present the typical patterns of transfer latencies that have been identified with the latency monitor.We identify the areas in PhEDEx where a development effort can reduce the latency, and we show how we are able to detect stuck transfers which need operator intervention. Lastly, we propose a set of metrics to alert about stuck subscriptions and prompt for manual intervention, with the aim of improving transfer completion times.« less

Moving beyond the comprehensive in vitro proarrhythmia assay: Use of human-induced pluripotent stem cell-derived cardiomyocytes to assess contractile effects associated with drug-induced structural cardiotoxicity.

PubMed

Yang, Xi; Papoian, Thomas

2018-02-27

Drug-induced cardiotoxicity is a potentially severe side effect that can adversely affect myocardial contractility through structural or electrophysiological changes in cardiomyocytes. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a promising human cardiac in vitro model system to assess both proarrhythmic and non-proarrhythmic cardiotoxicity of new drug candidates. The scalable differentiation of hiPSCs into cardiomyocytes provides a renewable cell source that overcomes species differences present in current animal models of drug toxicity testing. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative represents a paradigm shift for proarrhythmic risk assessment, and hiPSC-CMs are an integral component of that paradigm. The recent advancements in hiPSC-CMs will not only impact safety decisions for possible drug-induced proarrhythmia, but should also facilitate risk assessment for non-proarrhythmic cardiotoxicity, where current non-clinical approaches are limited in detecting this risk before initiation of clinical trials. Importantly, emerging evidence strongly suggests that the use of hiPSC-CMs with cardiac physiological relevant measurements in vitro improves the detection of structural cardiotoxicity. Here we review high-throughput drug screening using the hiPSC-CM model as an experimentally feasible approach to assess potential contractile and structural cardiotoxicity in early phase drug development. We also suggest that the assessment of structural cardiotoxicity can be added to electrophysiological tests in the same platform to complement the Comprehensive in vitro Proarrhythmia Assay for regulatory use. Ideally, application of these novel tools in early drug development will allow for more reliable risk assessment and lead to more informed regulatory decisions in making safe and effective drugs available to the public. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Comparative transcript profiling of alloplasmic male-sterile lines revealed altered gene expression related to pollen development in rice (Oryza sativa L.).

PubMed

Hu, Jihong; Chen, Guanglong; Zhang, Hongyuan; Qian, Qian; Ding, Yi

2016-08-05

Cytoplasmic male sterility (CMS) is an ideal model for investigating the mitochondrial-nuclear interaction and down-regulated genes in CMS lines which might be the candidate genes for pollen development in rice. In this study, a set of rice alloplasmic sporophytic CMS lines was obtained by successive backcrossing of Meixiang B, with three different cytoplasmic types: D62A (D type), ZS97A (WA type) and XQZ-A (DA type). Using microarray, the anther transcript profiles of the three indica rice CMS lines revealed 622 differentially expressed genes (DEGs) in each of the three CMS lines compared with the maintainer line Meixiang B. GO and MapMan analysis indicated that these DEGs were mainly involved in lipid metabolism and cell wall organization. Compared with the gene expression of sporophytic and gametophytic CMS lines, 303 DEGs were identified and 56 of them were down-regulated in all the CMS lines of rice. These down-regulated DEGs in the CMS lines were found to be involved in tapetum or cell wall formation and their suppressed expression might be related to male sterility. Weighted gene co-expression network analysis (WGCNA) revealed that two modules were significantly associated with male sterility and many hub genes that were differentially expressed in the CMS lines. A large set of putative genes involved in anther development was identified in the present study. The results will give some information for the nuclear gene regulation by different cytoplasmic genotypes and provide a rich resource for further functional research on the pollen development in rice.

Mesenchymal stem cells and their conditioned medium improve integration of purified induced pluripotent stem cell-derived cardiomyocyte clusters into myocardial tissue.

PubMed

Rubach, Martin; Adelmann, Roland; Haustein, Moritz; Drey, Florian; Pfannkuche, Kurt; Xiao, Bing; Koester, Annette; Udink ten Cate, Floris E A; Choi, Yeong-Hoon; Neef, Klaus; Fatima, Azra; Hannes, Tobias; Pillekamp, Frank; Hescheler, Juergen; Šarić, Tomo; Brockmeier, Konrad; Khalil, Markus

2014-03-15

Induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) might become therapeutically relevant to regenerate myocardial damage. Purified iPS-CMs exhibit poor functional integration into myocardial tissue. The aim of this study was to investigate whether murine mesenchymal stem cells (MSCs) or their conditioned medium (MScond) improves the integration of murine iPS-CMs into myocardial tissue. Vital or nonvital embryonic murine ventricular tissue slices were cocultured with purified clusters of iPS-CMs in combination with murine embryonic fibroblasts (MEFs), MSCs, or MScond. Morphological integration was assessed by visual scoring and functional integration by isometric force and field potential measurements. We observed a moderate morphological integration of iPS-CM clusters into vital, but a poor integration into nonvital, slices. MEFs and MSCs but not MScond improved morphological integration of CMs into nonvital slices and enabled purified iPS-CMs to confer force. Coculture of vital slices with iPS-CMs and MEFs or MSCs resulted in an improved electrical integration. A comparable improvement of electrical coupling was achieved with the cell-free MScond, indicating that soluble factors secreted by MSCs were involved in electrical coupling. We conclude that cells such as MSCs support the engraftment and adhesion of CMs, and confer force to noncontractile tissue. Furthermore, soluble factors secreted by MSCs mediate electrical coupling of purified iPS-CM clusters to myocardial tissue. These data suggest that MSCs may increase the functional engraftment and therapeutic efficacy of transplanted iPS-CMs into infarcted myocardium.

Mesenchymal Stem Cells and Their Conditioned Medium Improve Integration of Purified Induced Pluripotent Stem Cell–Derived Cardiomyocyte Clusters into Myocardial Tissue

PubMed Central

Rubach, Martin; Adelmann, Roland; Haustein, Moritz; Drey, Florian; Pfannkuche, Kurt; Xiao, Bing; Koester, Annette; Udink ten Cate, Floris E.A.; Choi, Yeong-Hoon; Neef, Klaus; Fatima, Azra; Hannes, Tobias; Pillekamp, Frank; Hescheler, Juergen; Šarić, Tomo; Brockmeier, Konrad

2014-01-01

Induced pluripotent stem cell–derived cardiomyocytes (iPS-CMs) might become therapeutically relevant to regenerate myocardial damage. Purified iPS-CMs exhibit poor functional integration into myocardial tissue. The aim of this study was to investigate whether murine mesenchymal stem cells (MSCs) or their conditioned medium (MScond) improves the integration of murine iPS-CMs into myocardial tissue. Vital or nonvital embryonic murine ventricular tissue slices were cocultured with purified clusters of iPS-CMs in combination with murine embryonic fibroblasts (MEFs), MSCs, or MScond. Morphological integration was assessed by visual scoring and functional integration by isometric force and field potential measurements. We observed a moderate morphological integration of iPS-CM clusters into vital, but a poor integration into nonvital, slices. MEFs and MSCs but not MScond improved morphological integration of CMs into nonvital slices and enabled purified iPS-CMs to confer force. Coculture of vital slices with iPS-CMs and MEFs or MSCs resulted in an improved electrical integration. A comparable improvement of electrical coupling was achieved with the cell-free MScond, indicating that soluble factors secreted by MSCs were involved in electrical coupling. We conclude that cells such as MSCs support the engraftment and adhesion of CMs, and confer force to noncontractile tissue. Furthermore, soluble factors secreted by MSCs mediate electrical coupling of purified iPS-CM clusters to myocardial tissue. These data suggest that MSCs may increase the functional engraftment and therapeutic efficacy of transplanted iPS-CMs into infarcted myocardium. PMID:24219308

A Novel Cytoplasmic Male Sterility in Brassica napus (inap CMS) with Carpelloid Stamens via Protoplast Fusion with Chinese Woad.

PubMed

Kang, Lei; Li, Pengfei; Wang, Aifan; Ge, Xianhong; Li, Zaiyun

2017-01-01

A novel cytoplasmic male sterility (CMS) in Brassica napus (inap CMS) was selected from the somatic hybrid with Isatis indigotica (Chinese woad) by recurrent backcrossing. The male sterility was caused by the conversion of tetradynamous stamens into carpelloid structures with stigmatoid tissues at their tips and ovule-like tissues in the margins, and the two shorter stamens into filaments without anthers. The feminized development of the stamens resulted in the complete lack of pollen grains, which was stable in different years and environments. The pistils of inap CMS displayed normal morphology and good seed-set after pollinated by B. napus . Histological sections showed that the developmental alteration of the stamens initiated at the stage of stamen primordium differentiation. AFLP analysis of the nuclear genomic composition with 23 pairs of selective primers detected no woad DNA bands in inap CMS. Twenty out of 25 mitochondrial genes originated from I. indigotica , except for cox2-2 which was the recombinant between cox2 from woad and cox2-2 from rapeseed. The novel cox2-2 was transcribed in flower buds of inap CMS weakly and comparatively with the fertile B. napus addition line Me harboring one particular woad chromosome. The restorers of other autoplasmic and alloplasmic CMS systems in rapeseed failed to restore the fertility of inap CMS and the screening of B. napus wide resources found no fertility restoration variety, showing its distinct origin and the related mechanism of sterility. The reasons for the mitochondrial rearrangements and the breeding of the restorer for the novel CMS system were discussed.

Biopharmaceutical classification of drugs using intrinsic dissolution rate (IDR) and rat intestinal permeability.

PubMed

Zakeri-Milani, Parvin; Barzegar-Jalali, Mohammad; Azimi, Mandana; Valizadeh, Hadi

2009-09-01

The solubility and dissolution rate of active ingredients are of major importance in preformulation studies of pharmaceutical dosage forms. In the present study, passively absorbed drugs are classified based on their intrinsic dissolution rate (IDR) and their intestinal permeabilities. IDR was determined by measuring the dissolution of a non-disintegrating disk of drug, and effective intestinal permeability of tested drugs in rat jejunum was determined using single perfusion technique. The obtained intrinsic dissolution rate values were in the range of 0.035-56.8 mg/min/cm(2) for tested drugs. The minimum and maximum intestinal permeabilities in rat intestine were determined to be 1.6 x 10(-5) and 2 x 10(-4)cm/s, respectively. Four classes of drugs were defined: Category I: P(eff,rat)>5 x 10(-5) (cm/s) or P(eff,human)>4.7 x 10(-5) (cm/s), IDR>1(mg/min/cm(2)), Category II: P(eff,rat)>5 x 10(-5) (cm/s) or P(eff,human)>4.7 x 10(-5) (cm/s), IDR<1(mg/min/cm(2)), Category III: P(eff,rat)<5 x 10(-5) (cm/s) or P(eff,human)<4.7 x 10(-5) (cm/s), IDR>1 (mg/min/cm(2)) and Category IV: P(eff,rat)<5 x 10(-5) (cm/s) or P(eff,human)<4.7 x 10(-5) (cm/s), IDR<1(mg/min/cm(2)). According to the results obtained and proposed classification of drugs, it is concluded that drugs could be categorized correctly based on their IDR and intestinal permeability values.

[Research survey on the information gathering methods, attitudes, and requests from care managers about the pharmaceutical service by pharmacists in home care].

PubMed

Nanaumi, Yoko; Onda, Mitsuko; Sakurai, Hidehiko; Tanaka, Rie; Tsubota, Kenichi; Matoba, Shunya; Mukai, Yusuke; Arakawa, Yukio; Hayase, Yukitoshi

2011-01-01

Care Managers (CMs) were surveyed to clarify the issues involving the promotion of cooperation between care managers and pharmacists in long-term-care and explore solutions. The length of work experience, occupational background, experience of pharmaceutical service; pharmacist visit patients' home for providing medicine and pharmaceutical care into a care plan, degree of understanding on pharmaceutical service, and awareness of work involved in pharmaceutical service were studied to see whether there made differences in the requests from CMs for information on pharmacists and for information gathering methods. The χ(2) test was used to this end. The opinions and requests described by the CMs were validated through text mining. More CMs tended to obtain information and knowledge through training sessions and professional magazines than those who did so through cooperation with pharmacists on a practical level. However, the survey strongly indicated that CMs with high level of understanding and awareness of pharmaceutical service wished to obtain information on pharmacists through cooperation with them on a practical level, and CMs with low level of understanding and awareness of pharmaceutical service wished to obtain such information through training sessions and professional magazines. Results of text mining showed that CMs wished pharmacists to strengthen the cooperation with physicians and provide information on pharmaceutical service. These findings have led to the conclusion that the issues surrounding the promotion of cooperation between CMs and pharmacists centered around "work cooperation on a practical level" and "provision of information to CMs about the roles of pharmacies and pharmacists and their work."

Comparison of American Academy of Sleep Medicine (AASM) versus Center for Medicare and Medicaid Services (CMS) polysomnography (PSG) scoring rules on AHI and eligibility for continuous positive airway pressure (CPAP) treatment.

PubMed

Korotinsky, Arkady; Assefa, Samson Z; Diaz-Abad, Montserrat; Wickwire, Emerson M; Scharf, Steven M

2016-12-01

Obstructive sleep apnea (OSA) is an important clinical condition. Eligibility for treatment usually depends on disease severity, measured as the apnea-hypopnea index (AHI), equal to the sum of apneas plus hypopneas per hour of sleep. There is divergence on scoring rules for hypopneas between the recommendations of the American Academy of Sleep Medicine (AASM) and the Center for Medicare Services (CMS), the latter being more restrictive. Thus, patients could be eligible for treatment under AASM rules, but not under CMS rules. Sleep laboratory records of 112 consecutive patients were reviewed (85 < 65, 27 ≥ 65 years old). AHI was calculated both by AASM and by CMS criteria. Information on demographics, and important comorbidities, was also reviewed. AHI was lower in younger patients using CMS criteria. However, differences in AHI using the two sets of criteria were not significantly different in the older patients. Incorporating all criteria for eligibility (severity, presence of certain comorbid conditions) for treatment, we found that fewer younger patients would be eligible using CMS criteria, but among the older patients, eligibility for treatment was the same whether AASM or CMS criteria were used. Use of CMS criteria for scoring hypopneas results in lower estimates of OSA severity, with fewer younger patients eligible for treatment. However, among Medicare age patients, the rate of treatment eligibility was the same whether AASM or CMS scoring rules were used.

The use of herbs by california midwives.

PubMed

Dennehy, Cathi; Tsourounis, Candy; Bui, Lindsey; King, Tekoa L

2010-01-01

To characterize herbal product use (prevalence, types, indications) among Certified Nurse Midwives/Certified Midwives (CNMs/CMs) and Licensed Midwives (LMs) practicing in the state of California and to describe formal education related to herbal products received by midwives during midwifery education. Cross-sectional survey/California/Practicing midwives. A list of LMs and CNMs/CMs practicing in California was obtained through the California Medical Board (CMB) and the American College of Nurse Midwives (ACNM), respectively. The survey was mailed to 343 CNMs/CMs (one third of the ACNM mailing list) and 157 LMs (the complete CMB mailing list). Of the 500 surveys mailed, 40 were undeliverable, 146 were returned, and 7 were excluded (30% response rate). Of the 139 completed surveys, 58/102 (57%) of CNMs/CMs and 35/37 (95%) of LMs used herbs, and LMs were more comfortable than CNMs/CMs in recommending herbs to their patients. A majority of LMs had >20 hours of midwifery education on herbs whereas a majority of CNMs/CMs received 0 to 5 hours. Some CNMs/CMs indicated that their practice site limited their ability to use herbs. Common conditions in which LMs and CNMs/CMs used herbs were nausea/vomiting (86% vs. 83%), labor induction (89% vs. 58%), and lactation (86% vs. 65%). Specific herbs for all indications are described. Licensed midwives were more likely than CNMs/CMs to use herbs in clinical practice. This trend was likely a reflection of the amount of education devoted to herbs as well as herbal use limitations that may be encountered in institutional facilities. © 2010 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

45 CFR 150.323 - Determining the amount of penalty-other matters as justice may require.

Code of Federal Regulations, 2010 CFR

2010-10-01

... REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS... Determining the amount of penalty—other matters as justice may require. CMS may take into account other...

Extensive structural variations between mitochondrial genomes of CMS and normal peppers (Capsicum annuum L.) revealed by complete nucleotide sequencing.

PubMed

Jo, Yeong Deuk; Choi, Yoomi; Kim, Dong-Hwan; Kim, Byung-Dong; Kang, Byoung-Cheorl

2014-07-04

Cytoplasmic male sterility (CMS) is an inability to produce functional pollen that is caused by mutation of the mitochondrial genome. Comparative analyses of mitochondrial genomes of lines with and without CMS in several species have revealed structural differences between genomes, including extensive rearrangements caused by recombination. However, the mitochondrial genome structure and the DNA rearrangements that may be related to CMS have not been characterized in Capsicum spp. We obtained the complete mitochondrial genome sequences of the pepper CMS line FS4401 (507,452 bp) and the fertile line Jeju (511,530 bp). Comparative analysis between mitochondrial genomes of peppers and tobacco that are included in Solanaceae revealed extensive DNA rearrangements and poor conservation in non-coding DNA. In comparison between pepper lines, FS4401 and Jeju mitochondrial DNAs contained the same complement of protein coding genes except for one additional copy of an atp6 gene (ψatp6-2) in FS4401. In terms of genome structure, we found eighteen syntenic blocks in the two mitochondrial genomes, which have been rearranged in each genome. By contrast, sequences between syntenic blocks, which were specific to each line, accounted for 30,380 and 17,847 bp in FS4401 and Jeju, respectively. The previously-reported CMS candidate genes, orf507 and ψatp6-2, were located on the edges of the largest sequence segments that were specific to FS4401. In this region, large number of small sequence segments which were absent or found on different locations in Jeju mitochondrial genome were combined together. The incorporation of repeats and overlapping of connected sequence segments by a few nucleotides implied that extensive rearrangements by homologous recombination might be involved in evolution of this region. Further analysis using mtDNA pairs from other plant species revealed common features of DNA regions around CMS-associated genes. Although large portion of sequence context was shared by mitochondrial genomes of CMS and male-fertile pepper lines, extensive genome rearrangements were detected. CMS candidate genes located on the edges of highly-rearranged CMS-specific DNA regions and near to repeat sequences. These characteristics were detected among CMS-associated genes in other species, implying a common mechanism might be involved in the evolution of CMS-associated genes.

Final Technical Report for ARRA Funding

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

Rusack, Roger; Mans, Jeremiah; Poling, Ronald

Final technical report of the University of Minnesota experimental high energy physics group for ARRA support. The Cryogenic Dark Matter Experiment (CDMS) used the funds received to construct a new passive shield to protect a high-purity germanium detector located in the Soudan mine in Northern Minnesota from cosmic rays. The BESIII and the CMS groups purchased computing hardware to assemble computer farms for data analysis and to generate large volumes of simulated data for comparison with the data collected.

Content management systems and E-commerce: a comparative case study

NASA Astrophysics Data System (ADS)

Al Rasheed, Amal A.; El-Masri, Samir D.

2011-12-01

The need for CMS's to create and edit e-commerce websites has increased with the growing importance of e-commerce. In this paper, the various features essential for e-commerce CMS's are explored. The aim of the paper was to find the best CMS solution for e-commerce which includes the best of both CMS and store management. Accordingly, we conducted a study on three popular open source CMS's for e-commerce: VirtueMart from Joomla!, Ubercart from Drupal, and Magento. We took into account features like hosting and installation, performance, support/community, content management, add on modules and functional features. We concluded with improvements that could be made in order to alleviate problems.

Using the CMS threaded framework in a production environment

DOE PAGES

Jones, C. D.; Contreras, L.; Gartung, P.; ...

2015-12-23

During 2014, the CMS Offline and Computing Organization completed the necessary changes to use the CMS threaded framework in the full production environment. We will briefly discuss the design of the CMS Threaded Framework, in particular how the design affects scaling performance. We will then cover the effort involved in getting both the CMSSW application software and the workflow management system ready for using multiple threads for production. Finally, we will present metrics on the performance of the application and workflow system as well as the difficulties which were uncovered. As a result, we will end with CMS' plans formore » using the threaded framework to do production for LHC Run 2.« less

Development of an expert system prototype for determining software functional requirements for command management activities at NASA Goddard

NASA Technical Reports Server (NTRS)

Liebowitz, J.

1985-01-01

The development of an expert system prototype for determining software functional requirements for NASA Goddard's Command Management System (CMS) is described. The role of the CMS is to transform general requests into specific spacecraft commands with command execution conditions. The CMS is part of the NASA Data System which entails the downlink of science and engineering data from NASA near-earth satellites to the user, and the uplink of command and control data to the spacecraft. Subjects covered include: the problem environment of determining CMS software functional requirements; the expert system approach for handling CMS requirements development; validation and evaluation procedures for the expert system.

Triggering on New Physics with the CMS Detector

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

Bose, Tulika

The BU CMS group led by PI Tulika Bose has made several significant contributions to the CMS trigger and to the analysis of the data collected by the CMS experiment. Group members have played a leading role in the optimization of trigger algorithms, the development of trigger menus, and the online operation of the CMS High-Level Trigger. The group’s data analysis projects have concentrated on a broad spectrum of topics that take full advantage of their strengths in jets and calorimetry, trigger, lepton identification as well as their considerable experience in hadron collider physics. Their publications cover several searches formore » new heavy gauge bosons, vector-like quarks as well as diboson resonances.« less

Beam test evaluation of electromagnetic calorimeter modules made from proton-damaged PbWO 4 crystals

DOE PAGES

Adams, T.; Adzic, P.; Ahuja, S.; ...

2016-04-11

The performance of electromagnetic calorimeter modules made of proton-irradiated PbWO 4 crystals has been studied in beam tests. The modules, similar to those used in the Endcaps of the CMS electromagnetic calorimeter (ECAL), were formed from 5×5 matrices of PbWO 4 crystals, which had previously been exposed to 24 GeV protons up to integrated fluences between 2.1 × 10 13 and 1.3 × 10 14 cm –2. These correspond to the predicted charged-hadron fluences in the ECAL Endcaps at pseudorapidity η = 2.6 after about 500 fb –1 and 3000 fb –1 respectively, corresponding to the end of the LHCmore » and High Luminosity LHC operation periods. The irradiated crystals have a lower light transmission for wavelengths corresponding to the scintillation light, and a correspondingly reduced light output. A comparison with four crystals irradiated in situ in CMS showed no significant rate dependence of hadron-induced damage. A degradation of the energy resolution and a non-linear response to electron showers are observed in damaged crystals. Direct measurements of the light output from the crystals show the amplitude decreasing and pulse becoming faster as the fluence increases. The latter is interpreted, through comparison with simulation, as a side-effect of the degradation in light transmission. In conclusion, the experimental results obtained can be used to estimate the long term performance of the CMS ECAL.« less

Development of an ion-pair to improve the colon permeability of a low permeability drug: Atenolol.

PubMed

Lozoya-Agullo, Isabel; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival

2016-10-10

To ensure the optimal performance of oral controlled release formulations, drug colon permeability is one of the critical parameters. Consequently developing this kind of formulations for low permeability molecules requires strategies to increase their ability to cross the colonic membrane. The objective of this work is to show if an ion-pair formation can improve the colon permeability of atenolol as a low permeability drug model. Two counter ions have been tested: brilliant blue and bromophenol blue. The Distribution coefficients at pH7.00 (DpH7) of atenolol, atenolol + brilliant blue and atenolol + bromophenol blue were experimentally determined in n-octanol. Moreover, the colonic permeability was determined in rat colon using in situ closed loop perfusion method based in Doluisio's Technique. To check the potential effects of the counter ions on the membrane integrity, a histological assessment of colonic tissue was done. The results of the partitioning studies were inconclusive about ion-pair formation; nevertheless colon permeability was significantly increased by both counter ions (from 0.232±0.021cm/s to 0.508±0.038cm/s in the presence of brilliant blue and to 0.405±0.044cm/s in the presence of bromophenol blue). Neither damage on the membrane was observed on the histological studies, nor any change on paracellular permeability suggesting that the permeability enhancement could be attributed to the ion-pair formation. Copyright © 2016 Elsevier B.V. All rights reserved.

Beam test evaluation of electromagnetic calorimeter modules made from proton-damaged PbWO 4 crystals

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

Adams, T.; Adzic, P.; Ahuja, S.

The performance of electromagnetic calorimeter modules made of proton-irradiated PbWO 4 crystals has been studied in beam tests. The modules, similar to those used in the Endcaps of the CMS electromagnetic calorimeter (ECAL), were formed from 5×5 matrices of PbWO 4 crystals, which had previously been exposed to 24 GeV protons up to integrated fluences between 2.1 × 10 13 and 1.3 × 10 14 cm –2. These correspond to the predicted charged-hadron fluences in the ECAL Endcaps at pseudorapidity η = 2.6 after about 500 fb –1 and 3000 fb –1 respectively, corresponding to the end of the LHCmore » and High Luminosity LHC operation periods. The irradiated crystals have a lower light transmission for wavelengths corresponding to the scintillation light, and a correspondingly reduced light output. A comparison with four crystals irradiated in situ in CMS showed no significant rate dependence of hadron-induced damage. A degradation of the energy resolution and a non-linear response to electron showers are observed in damaged crystals. Direct measurements of the light output from the crystals show the amplitude decreasing and pulse becoming faster as the fluence increases. The latter is interpreted, through comparison with simulation, as a side-effect of the degradation in light transmission. In conclusion, the experimental results obtained can be used to estimate the long term performance of the CMS ECAL.« less

Concurrent Flame Growth, Spread and Extinction over Composite Fabric Samples in Low Speed Purely Forced Flow in Microgravity

NASA Technical Reports Server (NTRS)

Zhao, Xiaoyang; T'ien, James S.; Ferkul, Paul V.; Olson, Sandra L.

2015-01-01

As a part of the NASA BASS and BASS-II experimental projects aboard the International Space Station, flame growth, spread and extinction over a composite cotton-fiberglass fabric blend (referred to as the SIBAL fabric) were studied in low-speed concurrent forced flows. The tests were conducted in a small flow duct within the Microgravity Science Glovebox. The fuel samples measured 1.2 and 2.2 cm wide and 10 cm long. Ambient oxygen was varied from 21% down to 16% and flow speed from 40 cm/s down to 1 cm/s. A small flame resulted at low flow, enabling us to observe the entire history of flame development including ignition, flame growth, steady spread (in some cases) and decay at the end of the sample. In addition, by decreasing flow velocity during some of the tests, low-speed flame quenching extinction limits were found as a function of oxygen percentage. The quenching speeds were found to be between 1 and 5 cm/s with higher speed in lower oxygen atmosphere. The shape of the quenching boundary supports the prediction by earlier theoretical models. These long duration microgravity experiments provide a rare opportunity for solid fuel combustion since microgravity time in ground-based facilities is generally not sufficient. This is the first time that a low-speed quenching boundary in concurrent spread is determined in a clean and unambiguous manner.

Epidemiological study of chronic mountain sickness in natives of Spiti Valley in the Greater Himalayas.

PubMed

Negi, Prakash Chand; Asotra, Sanjeev; V, Ravi Kumar; Marwah, Rajeev; Kandoria, Arvind; Ganju, Neeraj Kumar; Sharma, Rajesh; Bhardwaj, Rajeev

2013-09-01

This study determined the prevalence of chronic mountain sickness (CMS) and its predisposing factors among natives of Spiti Valley in the northern state of Indian Himalayas. A cross-sectional survey study was conducted in natives of Spiti Valley aged ≥ 20 years residing at altitudes of 3000 to 4200 meters. CMS was diagnosed using Qinghai criteria. Demographics, behavioral characteristics, specified symptoms of CMS were recorded, including BP, anthropometrics, evidence of RHF, PAH, and severe cyanosis. ECG, echocardiography, PFT, and Sao2 were recorded, and Hb level was estimated with the cyanmethhemoglobin method. 694 subjects free of cardiorespiratory diseases were analyzed. Prevalence of CMS was 28.7%, (95% C.I. of 25.9%-32.8%) and was higher in women than in men (36.6% vs. 15.7%, p<0.001). Erythrocythemia and hypoxemia were recorded in 10.5% and 7.5%, respectively. Age, truncal obesity, female gender, altitude of residence, and physical activity index were independent predictors of CMS with z statistics of 4.2, 2.29, -3.7, 2.8, and -2.8, respectively, and were statistically significant p<0.001. 6.2% of the surveyed population had HAPH. 28.7% (95% C.I. of 25.9%-32.8%) of the natives of the Spiti Valley in the Indian Himalayas are affected with CMS. Higher prevalence of CMS amongst women needs further studies. Westernized lifestyle appears to have predisposition to CMS.

Quantitative proteomic analysis of CMS-related changes in Honglian CMS rice anther.

PubMed

Sun, Qingping; Hu, Chaofeng; Hu, Jun; Li, Shaoqing; Zhu, Yingguo

2009-10-01

Honglian (HL) cytoplasmic male sterility (CMS) is one of the rice CMS types and has been widely used in hybrid rice production in China. The CMS line (Yuetai A, YTA) has a Yuetai B (maintainer line, YTB) nuclear genome, but has a rearranged mitochondrial (mt) genome consisting of Yuetai B. The fertility of hybrid (HL-6) was restored by restorer gene in nuclear genome of restorer line (9311). We used isotope-code affinity tag (ICAT) technology to perform the protein profiling of uninucleate stage rice anther and identify the CMS-HL related proteins. Two separate ICAT analyses were performed in this study: (1) anthers from YTA versus anthers from YTB, and (2) anthers from YTA versus anthers from HL-6. Based on the two analyses, a total of 97 unique proteins were identified and quantified in uninucleate stage rice anther under the error rate of less than 10%, of which eight proteins showed abundance changes of at least twofold between YTA and YTB. Triosephosphate isomerase, fructokinase II, DNA-binding protein GBP16 and ribosomal protein L3B were over-expressed in YTB, while oligopeptide transporter, floral organ regulator 1, kinase and S-adenosyl-L: -methionine synthetase were over-expressed in YTA. Reduction of the proteins associated with energy production and lesser ATP equivalents detected in CMS anther indicated that the low level of energy production played an important role in inducing CMS-HL.

Prediction of three social cognitive-motivational structure types.

PubMed

Malerstein, A J; Ahern, M M; Pulos, S

2001-10-01

Previously, using interviews from Baumrind's longitudinal study, three cognitive-motivational structures (CMSs) were predicted in 68 adolescents from caregiving settings and from the CMS types of their mothers, based on the mothers' interviews elicited six years earlier. CMS theory proposes that during Piaget's Concrete Operational Period care-receiving influences the child's adoption of a social cognitive style, which corresponds to one of Piaget's stages of cognitive development. One who is classified as an Operational experiences the caregiving setting as tuned to the child's long-term interests, becomes focused on function and control of function and grasps the distinctions between and gradations of social attributes. One classified as future Intuitive experiences the caregiving as insufficient or unreliable and becomes focused on getting and having, and assesses social situations based on current striking dimensions. A person classified as being future Symbolic experiences the caregiving as out of tune with the self or the world, becomes focused on identity and emotional closeness, and may define self or object by a single attribute. This previous study did not distinguish between the influence of caregiving (including mothers' CMS) on the formation of adolescent CMS type and the possible constancy of CMS type from ages 9 to 15 years. The current study was designed to distinguish between these two possibilities, using data from 67 of the same mothers. Mothers' interviews were purged of descriptions of her child's behavior. Another interview was composed of the purged descriptions of child behavior. This was also done for interviews held when the child was 4 and 15 as well as at 9. From interviews with descriptions of child behavior purged, mother's CMS type at the child's age of 4 and 9 yr. agreed with her adolescent's previously assigned CMS type (p<.05), and caregiving setting at 9 years predicted the adolescent's CMS type (p<.05). From interviews composed of descriptions of only the child's behavior, adolescent CMS type agreed with previously assigned adolescent CMS type (p<.01). Findings were consonant with the idea that CMS type formation is influenced at about Age 9 and sufficiently established to be recognized at Age 15.

Global transcriptomic analysis of induced cardiomyocytes predicts novel regulators for direct cardiac reprogramming.

PubMed

Talkhabi, Mahmood; Razavi, Seyed Morteza; Salari, Ali

2017-06-01

Heart diseases are the most significant cause of morbidity and mortality in the world. De novo generated cardiomyocytes (CMs) are a great cellular source for cell-based therapy and other potential applications. Direct cardiac reprogramming is the newest method to produce CMs, known as induced cardiomyocytes (iCMs). During a direct cardiac reprogramming, also known as transdifferentiation, non-cardiac differentiated adult cells are reprogrammed to cardiac identity by forced expression of cardiac-specific transcription factors (TFs) or microRNAs. To this end, many different combinations of TFs (±microRNAs) have been reported for direct reprogramming of mouse or human fibroblasts to iCMs, although their efficiencies remain very low. It seems that the investigated TFs and microRNAs are not sufficient for efficient direct cardiac reprogramming and other cardiac specific factors may be required for increasing iCM production efficiency, as well as the quality of iCMs. Here, we analyzed gene expression data of cardiac fibroblast (CFs), iCMs and adult cardiomyocytes (aCMs). The up-regulated and down-regulated genes in CMs (aCMs and iCMs) were determined as CM and CF specific genes, respectively. Among CM specific genes, we found 153 transcriptional activators including some cardiac and non-cardiac TFs that potentially activate the expression of CM specific genes. We also identified that 85 protein kinases such as protein kinase D1 (PKD1), protein kinase A (PRKA), calcium/calmodulin-dependent protein kinase (CAMK), protein kinase C (PRKC), and insulin like growth factor 1 receptor (IGF1R) that are strongly involved in establishing CM identity. CM gene regulatory network constructed using protein kinases, transcriptional activators and intermediate proteins predicted some new transcriptional activators such as myocyte enhancer factor 2A (MEF2A) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A), which may be required for qualitatively and quantitatively efficient direct cardiac reprogramming. Taken together, this study provides new insights into the complexity of cell fate conversion and better understanding of the roles of transcriptional activators, signaling pathways and protein kinases in increasing the efficiency of direct cardiac reprogramming and maturity of iCMs.

Comparison of the performance of the CMS Hierarchical Condition Category (CMS-HCC) risk adjuster with the Charlson and Elixhauser comorbidity measures in predicting mortality.

PubMed

Li, Pengxiang; Kim, Michelle M; Doshi, Jalpa A

2010-08-20

The Centers for Medicare and Medicaid Services (CMS) has implemented the CMS-Hierarchical Condition Category (CMS-HCC) model to risk adjust Medicare capitation payments. This study intends to assess the performance of the CMS-HCC risk adjustment method and to compare it to the Charlson and Elixhauser comorbidity measures in predicting in-hospital and six-month mortality in Medicare beneficiaries. The study used the 2005-2006 Chronic Condition Data Warehouse (CCW) 5% Medicare files. The primary study sample included all community-dwelling fee-for-service Medicare beneficiaries with a hospital admission between January 1st, 2006 and June 30th, 2006. Additionally, four disease-specific samples consisting of subgroups of patients with principal diagnoses of congestive heart failure (CHF), stroke, diabetes mellitus (DM), and acute myocardial infarction (AMI) were also selected. Four analytic files were generated for each sample by extracting inpatient and/or outpatient claims for each patient. Logistic regressions were used to compare the methods. Model performance was assessed using the c-statistic, the Akaike's information criterion (AIC), the Bayesian information criterion (BIC) and their 95% confidence intervals estimated using bootstrapping. The CMS-HCC had statistically significant higher c-statistic and lower AIC and BIC values than the Charlson and Elixhauser methods in predicting in-hospital and six-month mortality across all samples in analytic files that included claims from the index hospitalization. Exclusion of claims for the index hospitalization generally led to drops in model performance across all methods with the highest drops for the CMS-HCC method. However, the CMS-HCC still performed as well or better than the other two methods. The CMS-HCC method demonstrated better performance relative to the Charlson and Elixhauser methods in predicting in-hospital and six-month mortality. The CMS-HCC model is preferred over the Charlson and Elixhauser methods if information about the patient's diagnoses prior to the index hospitalization is available and used to code the risk adjusters. However, caution should be exercised in studies evaluating inpatient processes of care and where data on pre-index admission diagnoses are unavailable.

Sickle cell disease: reference values and interhemispheric differences of nonimaging transcranial Doppler blood flow parameters.

PubMed

Arkuszewski, M; Krejza, J; Chen, R; Kwiatkowski, J L; Ichord, R; Zimmerman, R; Ohene-Frempong, K; Desiderio, L; Melhem, E R

2011-09-01

TCD screening is widely used to identify children with SCD at high risk of stroke. Those with high mean flow velocities in major brain arteries have increased risk of stroke. Thus, our aim was to establish reference values of interhemispheric differences and ratios of blood flow Doppler parameters in the tICA, MCA, and ACA as determined by conventional TCD in children with sickle cell anemia. Reference limits of blood flow parameters were established on the basis of a consecutive cohort of 56 children (mean age, 100 ± 40 months; range, 29-180 months; 30 females) free of neurologic deficits and intracranial stenosis detectable by MRA, with blood flow velocities <170 cm/s by conventional TCD. Reference limits were estimated by using tolerance intervals, within which are included with a probability of .90 of all possible data values from 95% of a population. Average peak systolic velocities were significantly higher in the right hemisphere in the MCA and ACA (185 ± 28 cm/s versus 179 ± 27 and 152 ± 30 cm/s versus 143 ± 34 cm/s respectively). Reference limits for left-to-right differences in the mean flow velocities were the following: -43 to 33 cm/s for the MCA; -49 to 38 cm/s for the ACA, and -38 to 34 cm/s for the tICA, respectively. Respective reference limits for left-to-right velocity ratios were the following: 0.72 to 1.25 cm/s for the MCA; 0.62 to 1.39 cm/s for the ACA, and 0.69 to 1.27 cm/s for the tICA. Flow velocities in major arteries were inversely related to age and Hct or Hgb. The study provides reference intervals of TCD flow velocities and their interhemispheric differences and ratios that may be helpful in identification of intracranial arterial stenosis in children with SCD undergoing sonographic screening for stroke prevention.

Transcriptome sequencing and de novo analysis of cytoplasmic male sterility and maintenance in JA-CMS cotton.

PubMed

Yang, Peng; Han, Jinfeng; Huang, Jinling

2014-01-01

Cytoplasmic male sterility (CMS) is the failure to produce functional pollen, which is inherited maternally. And it is known that anther development is modulated through complicated interactions between nuclear and mitochondrial genes in sporophytic and gametophytic tissues. However, an unbiased transcriptome sequencing analysis of CMS in cotton is currently lacking in the literature. This study compared differentially expressed (DE) genes of floral buds at the sporogenous cells stage (SS) and microsporocyte stage (MS) (the two most important stages for pollen abortion in JA-CMS) between JA-CMS and its fertile maintainer line JB cotton plants, using the Illumina HiSeq 2000 sequencing platform. A total of 709 (1.8%) DE genes including 293 up-regulated and 416 down-regulated genes were identified in JA-CMS line comparing with its maintainer line at the SS stage, and 644 (1.6%) DE genes with 263 up-regulated and 381 down-regulated genes were detected at the MS stage. By comparing the two stages in the same material, there were 8 up-regulated and 9 down-regulated DE genes in JA-CMS line and 29 up-regulated and 9 down-regulated DE genes in JB maintainer line at the MS stage. Quantitative RT-PCR was used to validate 7 randomly selected DE genes. Bioinformatics analysis revealed that genes involved in reduction-oxidation reactions and alpha-linolenic acid metabolism were down-regulated, while genes pertaining to photosynthesis and flavonoid biosynthesis were up-regulated in JA-CMS floral buds compared with their JB counterparts at the SS and/or MS stages. All these four biological processes play important roles in reactive oxygen species (ROS) homeostasis, which may be an important factor contributing to the sterile trait of JA-CMS. Further experiments are warranted to elucidate molecular mechanisms of these genes that lead to CMS.

Transcriptome Sequencing and De Novo Analysis of Cytoplasmic Male Sterility and Maintenance in JA-CMS Cotton

PubMed Central

Yang, Peng; Han, Jinfeng; Huang, Jinling

2014-01-01

Cytoplasmic male sterility (CMS) is the failure to produce functional pollen, which is inherited maternally. And it is known that anther development is modulated through complicated interactions between nuclear and mitochondrial genes in sporophytic and gametophytic tissues. However, an unbiased transcriptome sequencing analysis of CMS in cotton is currently lacking in the literature. This study compared differentially expressed (DE) genes of floral buds at the sporogenous cells stage (SS) and microsporocyte stage (MS) (the two most important stages for pollen abortion in JA-CMS) between JA-CMS and its fertile maintainer line JB cotton plants, using the Illumina HiSeq 2000 sequencing platform. A total of 709 (1.8%) DE genes including 293 up-regulated and 416 down-regulated genes were identified in JA-CMS line comparing with its maintainer line at the SS stage, and 644 (1.6%) DE genes with 263 up-regulated and 381 down-regulated genes were detected at the MS stage. By comparing the two stages in the same material, there were 8 up-regulated and 9 down-regulated DE genes in JA-CMS line and 29 up-regulated and 9 down-regulated DE genes in JB maintainer line at the MS stage. Quantitative RT-PCR was used to validate 7 randomly selected DE genes. Bioinformatics analysis revealed that genes involved in reduction-oxidation reactions and alpha-linolenic acid metabolism were down-regulated, while genes pertaining to photosynthesis and flavonoid biosynthesis were up-regulated in JA-CMS floral buds compared with their JB counterparts at the SS and/or MS stages. All these four biological processes play important roles in reactive oxygen species (ROS) homeostasis, which may be an important factor contributing to the sterile trait of JA-CMS. Further experiments are warranted to elucidate molecular mechanisms of these genes that lead to CMS. PMID:25372034

Genetic control of invasive plants species using selfish genetic elements

PubMed Central

Hodgins, Kathryn A; Rieseberg, Loren; Otto, Sarah P

2009-01-01

Invasive plants cause substantial environmental damage and economic loss. Here, we explore the possibility that a selfish genetic element found in plants called cytoplasmic male sterility (CMS) could be exploited for weed control. CMS is caused by mutations in the mitochondrial genome that sterilize male reproductive organs. We developed an analytical model and a spatial simulation to assess the use of CMS alleles to manage weed populations. Specifically, we examined how fertility, selfing, pollen limitation and dispersal influenced extinction rate and time until extinction in populations where CMS arises. We found that the introduction of a CMS allele can cause rapid population extinction, but only under a restricted set of conditions. Both models suggest that the CMS strategy will be appropriate for species where pollen limitation is negligible, inbreeding depression is high and the fertility advantage of females over hermaphrodites is substantial. In general, spatial structure did not have a strong influence on the simulation outcome, although low pollen dispersal and intermediate levels of seed dispersal tended to reduce population extinction rates. Given these results, the introduction of CMS alleles into a population of invasive plants probably represents an effective control method for only a select number of species. PMID:25567898

A study on size effect of carboxymethyl starch nanogel crosslinked by electron beam radiation

NASA Astrophysics Data System (ADS)

Binh, Doan; Pham Thi Thu Hong; Nguyen Ngoc Duy; Nguyen Thanh Duoc; Nguyen Nguyet Dieu

2012-07-01

The formation of carboxymethyl starch (CMS) nanogel with 50 nm less particle size was carried out through a radiation crosslinked process on the electron beam (EB) linear accelerator. Changes of intrinsic viscosities and weight averaged molecular weight in the CMS concentration, which ranged from 3 to 10 mg ml-1 in absorbed doses were investigated. There were some new peaks in the 1H NMR spectra of CMS nanogel compared with those of CMS polymer. These results were anticipated that the predominant intramolecular crosslinking of dilute CMS aqueous solution occurred while being exposed to a short intense pulse of ionizing radiation. Hydrodynamic radius (often called particle size, Rh) and distribution of particle size were measured by a dynamic light scattering technique. The radiation yield of intermolecular crosslinking of CMS solution was calculated from the expression of Gx (Charlesby, 1960; Jung-Chul, 2010). The influence of the "size effect" was demonstrated by testing culture of Lactobacillus bacteria on MRS agar culture medium containing CMS nanogel and polymer. Results showed that the number of Lactobacillus bacteria growing on nanogel containing culture medium is about 170 cfu/ml and on polymer containing culture medium is only 6 cfu/ml.

Exploiting Analytics Techniques in CMS Computing Monitoring

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

Bonacorsi, D.; Kuznetsov, V.; Magini, N.

The CMS experiment has collected an enormous volume of metadata about its computing operations in its monitoring systems, describing its experience in operating all of the CMS workflows on all of the Worldwide LHC Computing Grid Tiers. Data mining efforts into all these information have rarely been done, but are of crucial importance for a better understanding of how CMS did successful operations, and to reach an adequate and adaptive modelling of the CMS operations, in order to allow detailed optimizations and eventually a prediction of system behaviours. These data are now streamed into the CERN Hadoop data cluster formore » further analysis. Specific sets of information (e.g. data on how many replicas of datasets CMS wrote on disks at WLCG Tiers, data on which datasets were primarily requested for analysis, etc) were collected on Hadoop and processed with MapReduce applications profiting of the parallelization on the Hadoop cluster. We present the implementation of new monitoring applications on Hadoop, and discuss the new possibilities in CMS computing monitoring introduced with the ability to quickly process big data sets from mulltiple sources, looking forward to a predictive modeling of the system.« less

Gender differences in CMS and the effects of antidepressant venlafaxine in rats.

PubMed

Xing, Yanli; He, Jie; Hou, Jian; Lin, Fei; Tian, Jingwei; Kurihara, Hiroshi

2013-11-01

Gender differences in susceptibility to chronic mild stress (CMS) and effects of venlafaxine in rats have been investigated in the current study. Male and female SD rats were exposed to CMS or CMS plus chronic venlafaxine administration (10mg/kg, 21days) in order to study depressive behavior in rats. Rats were tested in open field test and sucrose preference test to figure out gender differences in behavior. Then serum corticosterone and the expression of FKBP5 in hippocampus of rats were detected to explore the possible mechanism. The results showed that the CMS impact on behavioral parameters and corticosterone levels and response to venlafaxine were gender dependent. Female rats appeared more vulnerable in the dysregulation of HPA axis to CMS. Venlafaxine treatment normalized depressive-like behavior in both gender. However, venlafaxine treated male rats exhibited better improved explore behavior and anhedonia. FKBP5 might be involved in the explanation of gender differences in CMS and venlafaxine treatment. Male and female rats respond differently to chronic stress and venlafaxine continuous treatment. This results have guiding meaning in design of trials related to stress induced depression. Copyright © 2013 Elsevier Ltd. All rights reserved.

A quality improvement project to improve the Medicare and Medicaid Services (CMS) sepsis bundle compliance rate in a large healthcare system.

PubMed

Raschke, Robert A; Groves, Robert H; Khurana, Hargobind S; Nikhanj, Nidhi; Utter, Ethel; Hartling, Didi; Stoffer, Brenda; Nunn, Kristina; Tryon, Shona; Bruner, Michelle; Calleja, Maria; Curry, Steven C

2017-01-01

Sepsis is a leading cause of mortality and morbidity in hospitalised patients. The Centers for Medicare and Medicaid Services (CMS) mandated that US hospitals report sepsis bundle compliance rate as a quality process measure in October 2015. The specific aim of our study was to improve the CMS sepsis bundle compliance rate from 30% to 40% across 20 acute care hospitals in our healthcare system within 1 year. The study included all adult inpatients with sepsis sampled according to CMS specifications from October 2015 to September 2016. The CMS sepsis bundle compliance rate was tracked monthly using statistical process control charting. A baseline rate of 28.5% with 99% control limits was established. We implemented multiple interventions including computerised decision support systems (CDSSs) to increase compliance with the most commonly missing bundle elements. Compliance reached 42% (99% statistical process control limits 18.4%-38.6%) as CDSS was implemented system-wide, but this improvement was not sustained after CMS changed specifications of the outcome measure. Difficulties encountered elucidate shortcomings of our study methodology and of the CMS sepsis bundle compliance rate as a quality process measure.

76 FR 18766 - Early Retiree Reinsurance Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare & Medicaid Services [CMS-9996-N] Early Retiree Reinsurance Program AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Notice. SUMMARY: This notice announces that CMS is exercising its authority under section 1102(f) of the...

42 CFR 417.142 - Requirements for qualification.

Code of Federal Regulations, 2010 CFR

2010-10-01

....142 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... assurances specified in paragraphs (b) through (f) of this section, as appropriate. (2) CMS determines... entity, within 30 days of CMS's determination, provides written assurances, satisfactory to CMS, that it...

Using a 1200 kHz workhorse ADCP with mode 12 to measure near bottom mean currents

USGS Publications Warehouse

Martini, M.; ,

2003-01-01

Using high frequency Acoustic Doppler Current (ADCP) profiling technology, it is possible to make high-resolution measurements of mean current profiles within a few meters of the seabed. In coastal applications, mean current speeds may be 10 cm/s or less, and oscillatory wave currents may exceed 100 cm/s during storm events. To resolve mean flows of 10 cm/s or less under these conditions, accuracies of 1 cm/s or better are desirable.

42 CFR 414.410 - Phased-in implementation of competitive bidding programs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... largest MSAs by total population based on 2009 population estimates, and not already phased in as of June 1, 2008). CMS may subdivide any of the 91 MSAs with a population of greater than 8,000,000 into... population of less than 250,000. (iii) An area with low population density within an MSA not selected under...

42 CFR 414.410 - Phased-in implementation of competitive bidding programs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... largest MSAs by total population based on 2009 population estimates, and not already phased in as of June 1, 2008). CMS may subdivide any of the 91 MSAs with a population of greater than 8,000,000 into... population of less than 250,000. (iii) An area with low population density within an MSA not selected under...

42 CFR 414.410 - Phased-in implementation of competitive bidding programs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... largest MSAs by total population based on 2009 population estimates, and not already phased in as of June 1, 2008). CMS may subdivide any of the 91 MSAs with a population of greater than 8,000,000 into... population of less than 250,000. (iii) An area with low population density within an MSA not selected under...

Technical/ administrative options for managing tritium MCL exceedances in P-area groundwater and Steel Creek

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

Ross, J.

2017-04-01

This white paper was requested by the Core Team (United States Department of Energy [USDOE], United States Environmental Protection Agency [USEPA], and South Carolina Department of Health and Environmental Control [SCDHEC]) at the P-Area Groundwater (PAGW) Operable Unit (OU) Scoping Meeting held in January 2017 to discuss recent data and potential alternatives in support of a focused Corrective Measures Study/Feasibility Study (CMS/FS). This white paper presents an overview of the problem, and a range of technical and administrative options for addressing the tritium contamination in groundwater and Steel Creek. As tritium cannot be treated practicably, alternatives are limited to mediamore » transfer, containment and natural attenuation principally relying on radioactive decay. Using other groundwater OU decisions involving tritium as precedent, Savannah River Nuclear Solutions (SRNS) recommends that final tritium alternatives be evaluated in a CMS/FS, understanding that the likely preferred remedy will include natural attenuation with land use controls (LUCs). This is based on the inability to significantly reduce tritium impact to Steel Creek using an engineered solution as compared to natural attenuation. The timing of this evaluation could be conducted concurrently with the final remedy evaluation for volatile organic compounds (VOCs).« less

A search for aquifers of sand and gravel by electrical-resistivity methods in north-central New Castle County, Delaware

USGS Publications Warehouse

Spicer, H. Cecil; McCullough, Richard A.; Mack, Frederick K.

1955-01-01

A search for aquifers in an area immediately north of the Chesapeake and Delaware Canal in New Castle, Del., has been made by an electrical resistivity study.  The search located 32 sites that may be underlain by sand and gravel. The thicker deposits are significant with respect to the occurrence of ground water, and all of them are of interest as possible sources of sand and gravel for construction purposes, such as for highway construction.  The thickness of these deposits ranges from 4.4 feet to 77 feet, and the computed resistivity for these ranges from a low of 97,800 ohm-cms to a high of 423,800 ohm-cms.  The study located with certainty one buried channel filled with sand and gravel deposits and pointed out the possibility of others that may be aquifers.  The interpretations show that a large deposit of sand and gravel is present in the eastern part of the area investigated and it is tentatively assumed that this deposit is continuous and may yield large quantities of ground water.  Places where the deposit was found to be the thickest and of high resistivity are described.

Chronic mild stress in submissive mice: Marked polydipsia and social avoidance without hedonic deficit in the sucrose preference test.

PubMed

Gross, Moshe; Pinhasov, Albert

2016-02-01

In the Chronic Mild Stress (CMS) protocol, rodents are exposed to unpredictable stressors to induce anxiety-like behavior and hedonic deficit in the Sucrose Preference test (SPT). Since CMS-induced anxiety- and anhedonic-like behavior may depend upon individual vulnerability to stress, we hypothesized that selectively bred Submissive (Sub) mice would exhibit heightened anxiety- and anhedonic-like behavior, in response to CMS exposure. We anticipated that the testing of Sub mice alongside their Wt counterparts in a battery of behavioral assays would identify parameters most sensitive to CMS effects. To test these assumptions, Sub mice and their outbred Sabra (Wt) counterparts underwent a five-week CMS-SPT regimen. CMS exposure led to reduced preference for sucrose (sucrose-sweetened water as percent of total intake) among both mouse strains (p<0.01 Wt; p<0.05 Sub). However, this effect was attributed to CMS-induced polydipsia, indicated by mice's increased water consumption, (p<0.01 Wt and Sub), without changes in sucrose intake. Furthermore, CMS-exposed Sub mice, but not Wt, demonstrated impaired social exploration in the Three Chamber test (p<0.05) and anxiety-like effects in the Elevated Plus Maze (p<0.05). Moreover, in a separate experiment, social isolation alone was sufficient to induce polydipsia in Sub mice, without affecting Wt mice's drinking behavior. The present findings suggest that the EPM and Three Chamber tests may be valuable complementary measures of CMS effects, alongside the Sucrose Preference test, and introduce the Sub mouse strain for use in study of susceptibility to stress. Copyright © 2015 Elsevier B.V. All rights reserved.

Transcriptome dynamics of human pluripotent stem cell-derived contracting cardiomyocytes using an embryoid body model with fetal bovine serum.

PubMed

Jung, Kwang Bo; Son, Ye Seul; Lee, Hana; Jung, Cho-Rok; Kim, Janghwan; Son, Mi-Young

2017-07-25

Cardiomyocyte (CM) differentiation techniques for generating adult-like mature CMs remain imperfect, and the plausible underlying mechanisms remain unclear; however, there are a number of current protocols available. Here, to explore the mechanisms controlling cardiac differentiation, we analyzed the genome-wide transcription dynamics occurring during the differentiation of human pluripotent stem cells (hPSCs) into CMs using embryoid body (EB) formation. We optimized and updated the protocol to efficiently generate contracting CMs from hPSCs by adding fetal bovine serum (FBS) as a medium supplement, which could have a significant impact on the efficiency of cardiac differentiation. To identify genes, biological processes, and pathways involved in the cardiac differentiation of hPSCs, integrative and comparative analyses of the transcriptome profiles of differentiated CMs from hPSCs and of control CMs of the adult human heart (CM-AHH) were performed using gene ontology, functional annotation clustering, and pathway analyses. Several genes commonly regulated in the differentiated CMs and CM-AHH were enriched in pathways related to cell cycle and nucleotide metabolism. Strikingly, we found that current differentiation protocols did not promote sufficient expression of genes involved in oxidative phosphorylation to differentiate CMs from hPSCs compared to the expression levels in CM-AHH. Therefore, to obtain mature CMs similar to CM-AHH, these deficient pathways in CM differentiation, such as energy-related pathways, must be augmented prior to use for in vitro and in vivo applications. This approach opens up new avenues for facilitating the utilization of hPSC-derived CMs in biomedical research, drug evaluation, and clinical applications for patients with cardiac failure.

Pompe Disease Results in a Golgi-based Glycosylation Deficit in Human Induced Pluripotent Stem Cell-derived Cardiomyocytes*

PubMed Central

Raval, Kunil K.; Tao, Ran; White, Brent E.; De Lange, Willem J.; Koonce, Chad H.; Yu, Junying; Kishnani, Priya S.; Thomson, James A.; Mosher, Deane F.; Ralphe, John C.; Kamp, Timothy J.

2015-01-01

Infantile-onset Pompe disease is an autosomal recessive disorder caused by the complete loss of lysosomal glycogen-hydrolyzing enzyme acid α-glucosidase (GAA) activity, which results in lysosomal glycogen accumulation and prominent cardiac and skeletal muscle pathology. The mechanism by which loss of GAA activity causes cardiomyopathy is poorly understood. We reprogrammed fibroblasts from patients with infantile-onset Pompe disease to generate induced pluripotent stem (iPS) cells that were differentiated to cardiomyocytes (iPSC-CM). Pompe iPSC-CMs had undetectable GAA activity and pathognomonic glycogen-filled lysosomes. Nonetheless, Pompe and control iPSC-CMs exhibited comparable contractile properties in engineered cardiac tissue. Impaired autophagy has been implicated in Pompe skeletal muscle; however, control and Pompe iPSC-CMs had comparable clearance rates of LC3-II-detected autophagosomes. Unexpectedly, the lysosome-associated membrane proteins, LAMP1 and LAMP2, from Pompe iPSC-CMs demonstrated higher electrophoretic mobility compared with control iPSC-CMs. Brefeldin A induced disruption of the Golgi in control iPSC-CMs reproduced the higher mobility forms of the LAMPs, suggesting that Pompe iPSC-CMs produce LAMPs lacking appropriate glycosylation. Isoelectric focusing studies revealed that LAMP2 has a more alkaline pI in Pompe compared with control iPSC-CMs due largely to hyposialylation. MALDI-TOF-MS analysis of N-linked glycans demonstrated reduced diversity of multiantennary structures and the major presence of a trimannose complex glycan precursor in Pompe iPSC-CMs. These data suggest that Pompe cardiomyopathy has a glycan processing abnormality and thus shares features with hypertrophic cardiomyopathies observed in the congenital disorders of glycosylation. PMID:25488666

A Novel Cytoplasmic Male Sterility in Brassica napus (inap CMS) with Carpelloid Stamens via Protoplast Fusion with Chinese Woad

PubMed Central

Kang, Lei; Li, Pengfei; Wang, Aifan; Ge, Xianhong; Li, Zaiyun

2017-01-01

A novel cytoplasmic male sterility (CMS) in Brassica napus (inap CMS) was selected from the somatic hybrid with Isatis indigotica (Chinese woad) by recurrent backcrossing. The male sterility was caused by the conversion of tetradynamous stamens into carpelloid structures with stigmatoid tissues at their tips and ovule-like tissues in the margins, and the two shorter stamens into filaments without anthers. The feminized development of the stamens resulted in the complete lack of pollen grains, which was stable in different years and environments. The pistils of inap CMS displayed normal morphology and good seed-set after pollinated by B. napus. Histological sections showed that the developmental alteration of the stamens initiated at the stage of stamen primordium differentiation. AFLP analysis of the nuclear genomic composition with 23 pairs of selective primers detected no woad DNA bands in inap CMS. Twenty out of 25 mitochondrial genes originated from I. indigotica, except for cox2-2 which was the recombinant between cox2 from woad and cox2-2 from rapeseed. The novel cox2-2 was transcribed in flower buds of inap CMS weakly and comparatively with the fertile B. napus addition line Me harboring one particular woad chromosome. The restorers of other autoplasmic and alloplasmic CMS systems in rapeseed failed to restore the fertility of inap CMS and the screening of B. napus wide resources found no fertility restoration variety, showing its distinct origin and the related mechanism of sterility. The reasons for the mitochondrial rearrangements and the breeding of the restorer for the novel CMS system were discussed. PMID:28428799

Neurodegenerative evidences during early onset of depression in CMS rats as detected by proton magnetic resonance spectroscopy at 7 T.

PubMed

Hemanth Kumar, B S; Mishra, Sushanta Kumar; Rana, Poonam; Singh, Sadhana; Khushu, Subash

2012-06-15

Depression is a complex psychiatric disorder characterized by anhedonia and feeling of sadness and chronic mild stress (CMS) seems to be a valuable animal model of depression. CMS animal model was induced and validated using behavioral studies. In the present study we investigated the neuro-metabolite changes occurring in prefrontal cortex and hippocampus during the onset of depression, in CMS rat model using in vivo proton magnetic resonance spectroscopy ((1)H MRS) at field strength of 7 T. Results showed that CMS caused depression-like behavior in rats, as indicated by the decrease in sucrose consumption and locomotor activity. (1)H MRS was performed in both control and CMS rats (n=10, in each group) and the quantitative assessment of the neurometabolites was done using LC model. Relative concentrations of all the metabolites along with the macromolecules were calculated for analysis. The results revealed a significant decrease of glutamate (Glu), glutamine (Gln), NAA+NAAG, Glx and GABA levels in both hippocampus and prefrontal cortex of CMS animals and an elevated level of myo-ionisitol (mI) and taurine (Tau) was observed only in hippocampus. These metabolite fluctuations revealed by proton MRS indicate that there might be change in the neuronal integrity of the glial cells and neurons within prefrontal cortex and hippocampus in CMS model of depression. The present study also suggests that there may be a degenerative process concerning the brain morphology in the CMS rats. The overall finding using (1)H MRS suggests that, there might be a major role of the glia and neuron in the onset of depression. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of priming cooperation or individualism on a collective and interdependent task: changeover speed in the 4 x 100-meter relay race.

PubMed

Bry, Clémentine; Meyer, Thierry; Oberlé, Dominique; Gherson, Thibault

2009-06-01

Priming effects of cooperation vs. individualism were investigated on changeover speed within a 4 x 100-m relay race. Ten teams of four adult beginner athletes ran two relays, a pretest race and an experimental race 3 weeks later. Just before the experimental race, athletes were primed with either cooperation or individualism through a scrambled-sentence task. Comparing to the pretest performance, cooperation priming improved baton speed in the exchange zone (+30 cm/s). Individualism priming did not impair changeover performance. The boundary conditions of priming effects applied to collective and interdependent tasks are discussed within the implicit coordination framework.

Hospitals push back against reimbursement cuts due to Two-Midnight rule.

PubMed

2016-04-01

The American Hospital Association (AHA) and other hospitals are suing CMS, challenging the 0.2% cut in Medicare reimbursement that CMS instituted to compensate for the financial effect of the Two-Midnight rule. CMS' actuaries reported that inpatient claims are likely to increase under the rule, resulting in $220 million additional reimbursement for hospitals. Hospitals disagree and a study commissioned by the AHA concluded that the CMS study was based on data not available to the public and that data from the Medicare Provider and Analysis Review (MedPAR) would lead to a different conclusion. The AHA suit asks CMS to rescind the cut, restore the base rate for Medicare payments to its previous level, and reimburse hospitals retroactively for the reductions.

User and group storage management the CMS CERN T2 centre

NASA Astrophysics Data System (ADS)

Cerminara, G.; Franzoni, G.; Pfeiffer, A.

2015-12-01

A wide range of detector commissioning, calibration and data analysis tasks is carried out by CMS using dedicated storage resources available at the CMS CERN Tier-2 centre. Relying on the functionalities of the EOS disk-only storage technology, the optimal exploitation of the CMS user/group resources has required the introduction of policies for data access management, data protection, cleanup campaigns based on access pattern, and long term tape archival. The resource management has been organised around the definition of working groups and the delegation to an identified responsible of each group composition. In this paper we illustrate the user/group storage management, and the development and operational experience at the CMS CERN Tier-2 centre in the 2012-2015 period.

45 CFR 150.219 - Final determination.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for Determining Whether States... substantially enforce, CMS finds that the failure to substantially enforce has not been corrected, it will send...

45 CFR 150.215 - Extension for good cause.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for Determining Whether States Are Failing To Substantially Enforce HIPAA Requirements § 150.215 Extension for good cause. CMS may...

45 CFR 150.217 - Preliminary determination.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS ENFORCEMENT IN GROUP AND INDIVIDUAL INSURANCE MARKETS CMS Enforcement Processes for Determining Whether States... the end of the 30-day period (and any extension), the State has not established to CMS's satisfaction...

The anti-CMS technique for genome-wide mapping of 5-hydroxymethylcytosine.

PubMed

Huang, Yun; Pastor, William A; Zepeda-Martínez, Jorge A; Rao, Anjana

2012-10-01

5-Hydroxymethylcytosine (5hmC) is a recently discovered base in the mammalian genome, produced upon oxidation of 5-methylcytosine (5mC) in a process catalyzed by TET proteins. The biological functions of 5hmC and further oxidation products of 5mC are under intense investigation, as they are likely intermediates in DNA demethylation pathways. Here we describe a novel protocol to profile 5hmC at a genome-wide scale. This approach is based on sodium bisulfite-mediated conversion of 5hmC to cytosine-5-methylenesulfonate (CMS); CMS-containing DNA fragments are then immunoprecipitated using a CMS-specific antiserum. The anti-CMS technique is highly specific with a low background, and is much less dependent on 5hmC density than anti-5hmC immunoprecipitation (IP). Moreover, it does not enrich for CA and CT repeats, as noted for 5hmC DNA IP using antibodies to 5hmC. The anti-CMS protocol takes 3 d to complete.

The chronic mild stress (CMS) model of depression: History, evaluation and usage.

PubMed

Willner, Paul

2017-02-01

Now 30 years old, the chronic mild stress (CMS) model of depression has been used in >1300 published studies, with a year-on-year increase rising to >200 papers in 2015. Data from a survey of users show that while a variety of names are in use (chronic mild/unpredictable/varied stress), these describe essentially the same procedure. This paper provides an update on the validity and reliability of the CMS model, and reviews recent data on the neurobiological basis of CMS effects and the mechanisms of antidepressant action: the volume of this research may be unique in providing a comprehensive account of antidepressant action within a single model. Also discussed is the use of CMS in drug discovery, with particular reference to hippocampal and extra-hippocampal targets. The high translational potential of the CMS model means that the neurobiological mechanisms described may be of particular relevance to human depression and mechanisms of clinical antidepressant action.

Leveraging the big-data revolution: CMS is expanding capabilities to spur health system transformation.

PubMed

Brennan, Niall; Oelschlaeger, Allison; Cox, Christine; Tavenner, Marilyn

2014-07-01

As the largest single payer for health care in the United States, the Centers for Medicare and Medicaid Services (CMS) generates enormous amounts of data. Historically, CMS has faced technological challenges in storing, analyzing, and disseminating this information because of its volume and privacy concerns. However, rapid progress in the fields of data architecture, storage, and analysis--the big-data revolution--over the past several years has given CMS the capabilities to use data in new and innovative ways. We describe the different types of CMS data being used both internally and externally, and we highlight a selection of innovative ways in which big-data techniques are being used to generate actionable information from CMS data more effectively. These include the use of real-time analytics for program monitoring and detecting fraud and abuse and the increased provision of data to providers, researchers, beneficiaries, and other stakeholders. Project HOPE—The People-to-People Health Foundation, Inc.

Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy.

PubMed

Cho, Gun-Sik; Lee, Dong I; Tampakakis, Emmanouil; Murphy, Sean; Andersen, Peter; Uosaki, Hideki; Chelko, Stephen; Chakir, Khalid; Hong, Ingie; Seo, Kinya; Chen, Huei-Sheng Vincent; Chen, Xiongwen; Basso, Cristina; Houser, Steven R; Tomaselli, Gordon F; O'Rourke, Brian; Judge, Daniel P; Kass, David A; Kwon, Chulan

2017-01-10

Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs). Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which manifests predominantly in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy

PubMed Central

Cho, Gun-Sik; Lee, Dong I.; Tampakakis, Emmanouil; Murphy, Sean; Andersen, Peter; Uosaki, Hideki; Chelko, Stephen; Chakir, Khalid; Hong, Ingie; Seo, Kinya; Vincent Chen, Huei-Sheng; Chen, Xiongwen; Basso, Cristina; Houser, Steven R.; Tomaselli, Gordon F.; O’Rourke, Brian; Judge, Daniel P.; Kass, David A.; Kwon, Chulan

2016-01-01

SUMMARY Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs). Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of the transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which predominantly manifests in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases. PMID:28076798

China's Rural Cooperative Medical Scheme: a type of health insurance or a type of health cooperative?

PubMed

Wang, Fang; Liang, Yuan

2017-03-01

The Cooperative Medical Scheme (CMS) was popular in rural China in the 1960s and 1970s, having garnered praise from the World Bank and World Health Organization as an unprecedented example of a successful health care model in a low-income developing country. However, the CMS almost collapsed in the 1980s. Based on its historical origins and main activities, we think the CMS functioned as a health cooperative rather than a health insurance scheme. Perhaps, however, the importance to the CMS of cooperation between institutions has been overestimated. Overlooked, yet equally important, has been the cooperation between health workers and farmers to target health-related risk factors associated with agricultural work and ways of life. The 'cooperative' character of the CMS includes two aspects: cooperative institutions and cooperative behaviour. Although the CMS collapsed in China, similar schemes are flourishing elsewhere in the world. In the future, in-depth analysis of these schemes is required.

Space Station Environmental Control and Life Support System Test Facility at Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Springer, Darlene

1989-01-01

Different aspects of Space Station Environmental Control and Life Support System (ECLSS) testing are currently taking place at Marshall Space Flight Center (MSFC). Unique to this testing is the variety of test areas and the fact that all are located in one building. The north high bay of building 4755, the Core Module Integration Facility (CMIF), contains the following test areas: the Subsystem Test Area, the Comparative Test Area, the Process Material Management System (PMMS), the Core Module Simulator (CMS), the End-use Equipment Facility (EEF), and the Pre-development Operational System Test (POST) Area. This paper addresses the facility that supports these test areas and briefly describes the testing in each area. Future plans for the building and Space Station module configurations will also be discussed.

Proarrhythmia risk prediction using human induced pluripotent stem cell-derived cardiomyocytes.

PubMed

Yamazaki, Daiju; Kitaguchi, Takashi; Ishimura, Masakazu; Taniguchi, Tomohiko; Yamanishi, Atsuhiro; Saji, Daisuke; Takahashi, Etsushi; Oguchi, Masao; Moriyama, Yuta; Maeda, Sanae; Miyamoto, Kaori; Morimura, Kaoru; Ohnaka, Hiroki; Tashibu, Hiroyuki; Sekino, Yuko; Miyamoto, Norimasa; Kanda, Yasunari

2018-04-01

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are expected to become a useful tool for proarrhythmia risk prediction in the non-clinical drug development phase. Several features including electrophysiological properties, ion channel expression profile and drug responses were investigated using commercially available hiPSC-CMs, such as iCell-CMs and Cor.4U-CMs. Although drug-induced arrhythmia has been extensively examined by microelectrode array (MEA) assays in iCell-CMs, it has not been fully understood an availability of Cor.4U-CMs for proarrhythmia risk. Here, we evaluated the predictivity of proarrhythmia risk using Cor.4U-CMs. MEA assay revealed linear regression between inter-spike interval and field potential duration (FPD). The hERG inhibitor E-4031 induced reverse-use dependent FPD prolongation. We next evaluated the proarrhythmia risk prediction by a two-dimensional map, which we have previously proposed. We determined the relative torsade de pointes risk score, based on the extent of FPD with Fridericia's correction (FPDcF) change and early afterdepolarization occurrence, and calculated the margins normalized to free effective therapeutic plasma concentrations. The drugs were classified into three risk groups using the two-dimensional map. This risk-categorization system showed high concordance with the torsadogenic information obtained by a public database CredibleMeds. Taken together, these results indicate that Cor.4U-CMs can be used for drug-induced proarrhythmia risk prediction. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Risk factors for covered metallic stent migration in patients with distal malignant biliary obstruction due to pancreatic cancer.

PubMed

Nakai, Yousuke; Isayama, Hiroyuki; Kogure, Hirofumi; Hamada, Tsuyoshi; Togawa, Osamu; Ito, Yukiko; Matsubara, Saburo; Arizumi, Toshihiko; Yagioka, Hiroshi; Mizuno, Suguru; Sasaki, Takashi; Yamamoto, Natsuyo; Hirano, Kenji; Tada, Minoru; Koike, Kazuhiko

2014-09-01

Covered metallic stents (CMSs) were developed to overcome tumor ingrowth in uncovered metallic stents (UMSs) for malignant biliary obstruction, but superiority of CMSs over UMSs is still controversial due to the high migration rate in CMS. Therefore, we conducted this retrospective analysis to clarify risk factors for stent migration, including mechanical properties of CMSs. Patients with unresectable pancreatic cancer, receiving CMS for distal malignant biliary obstruction in five tertiary care centers, were retrospectively studied. Univariate and multivariate analyses to identify prognostic factors for early (< 6 months) stent migration were performed using a proportional hazards model with death or stent occlusion without stent migration as a competing risk. Two mechanical properties were included in the analysis: axial force, the recovery force that leads to a CMS straightening, and radial force (RF), the expansion force against the stricture. Among 290 patients who received CMS placement for distal malignant biliary obstruction, stent migration rate was 15.2%. CMS migrated early (< 6 months) in 10.0% and distally in 11.7%, respectively. In the multivariate analysis, significant risk factors for early stent migration were chemotherapy (subdistribution hazard ratios [SHR] 4.46, P = 0.01), CMS with low RF (SHR 2.23, P = 0.03), and duodenal invasion (SHR 2.25, P = 0.02). CMS with low RF, chemotherapy, and duodenal invasion were associated with CMS migration from our study. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Neuropsychological function in children with primary complex motor stereotypies.

PubMed

Mahone, E Mark; Ryan, Matthew; Ferenc, Lisa; Morris-Berry, Christina; Singer, Harvey S

2014-10-01

Complex motor stereotypies (CMS) are patterned, repetitive, rhythmic, and involuntary movements that persist over time. They are divided into two subgroups dependent on the presence of other developmental problems: 'primary' (development is otherwise typical) or 'secondary' (associated with autism, intellectual disability, or sensory deficits). There are no currently published studies that examine neuropsychological function in children with primary CMS. This case-control study examines whether children with primary CMS manifest neurobehavioral deficits. Fifty-seven children with primary CMS (32 males, 25 females; mean age 6y 8mo, SD 2y 4mo, range 4-12y) with negative screens for autism and 57 comparison participants (32 males, 25 females; mean age 6y 6mo, SD 2y 1mo) completed neuropsychological assessments of IQ, reading ability, attention, language, and motor and executive functions. Parents completed ratings of their child's repetitive movement severity. The CMS group performed significantly less well than comparison participants on motor skills and IQ tests (both p<0.01), although IQ was consistently in the average range. One-third of the CMS group showed signs of developmental motor coordination difficulties. Parent report of stereotypy severity was significantly associated with parent report of inattention and executive dysfunction. Children with primary CMS were found to have largely intact neuropsychological profiles. Stereotypy severity appears to be associated with executive dysfunction. Although motor difficulties were observed in children with CMS, these were not correlated with parent report of symptom severity. © 2014 Mac Keith Press.

Large scale commissioning and operational experience with tier-2 to tier-2 data transfer links in CMS

NASA Astrophysics Data System (ADS)

Letts, J.; Magini, N.

2011-12-01

Tier-2 to Tier-2 data transfers have been identified as a necessary extension of the CMS computing model. The Debugging Data Transfers (DDT) Task Force in CMS was charged with commissioning Tier-2 to Tier-2 PhEDEx transfer links beginning in late 2009, originally to serve the needs of physics analysis groups for the transfer of their results between the storage elements of the Tier-2 sites associated with the groups. PhEDEx is the data transfer middleware of the CMS experiment. For analysis jobs using CRAB, the CMS Remote Analysis Builder, the challenges of remote stage out of job output at the end of the analysis jobs led to the introduction of a local fallback stage out, and will eventually require the asynchronous transfer of user data over essentially all of the Tier-2 to Tier-2 network using the same PhEDEx infrastructure. In addition, direct file sharing of physics and Monte Carlo simulated data between Tier-2 sites can relieve the operational load of the Tier-1 sites in the original CMS Computing Model, and already represents an important component of CMS PhEDEx data transfer volume. The experience, challenges and methods used to debug and commission the thousands of data transfers links between CMS Tier-2 sites world-wide are explained and summarized. The resulting operational experience with Tier-2 to Tier-2 transfers is also presented.

Development of a Sensitive and Specific Polyclonal Antibody for Serological Detection of Clavibacter michiganensis subsp. sepedonicus

PubMed Central

Przewodowska, Agnieszka

2017-01-01

The quarantine bacterium Clavibacter michiganensis subsp. sepedonicus (Cms) causes bacterial ring rot (BRR) in potato but is difficult to detect, hampering the diagnosis of this disease. ELISA immunoassays have not been widely used to detect Cms because commercially available anti-Cms antibodies detect mainly EPS-producing bacteria and can fail to detect strains that do not produce EPS. In the current study, we developed a new type of polyclonal antibody that specifically detects Clavibacter michiganensis subsp. sepedonicus bacteria irrespective of their EPS level. We first found that the presence of bacterial EPS precluded quantitative measurement of bacteria by currently available immunoenzymatic methods, but that washing Cms cells with acidic and basic buffers to remove EPS before analysis successfully standardized ELISA results. We used a mix of three strains of Cms with diverse EPS levels to generate antigen for production of antibodies recognizing Cms cells with and without an EPS layer (IgG-EPS and IgG-N-EPS, respectively). The resulting IgG-N-EPS recognized almost all Cms strains tested in this work regardless of their mucoidal level. The availability of this new antibody renders immunological diagnostics of Cms more sensitive and reliable, as our newly developed antibodies can be used in many type of immunoassays. This work represents an important step forward in efforts to diagnose and prevent the spread of BRR, and the methods and solutions developed in this work are covered by six Polish, one European and one US patents. PMID:28068400

78 FR 62636 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-22

... the following transmissions: OMB, Office of Information and Regulatory Affairs, Attention: CMS Desk... Identifiers: CMS-10486] Agency Information Collection Activities: Submission for OMB Review; Comment Request... for the public to comment on CMS' intention to collect information from the public. Under the...

23 CFR 970.214 - Federal lands congestion management system (CMS).

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Federal lands congestion management system (CMS). 970... LANDS HIGHWAYS NATIONAL PARK SERVICE MANAGEMENT SYSTEMS National Park Service Management Systems § 970.214 Federal lands congestion management system (CMS). (a) For purposes of this section, congestion...

42 CFR 422.210 - Assurances to CMS.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Assurances to CMS. 422.210 Section 422.210 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM MEDICARE ADVANTAGE PROGRAM Relationships With Providers § 422.210 Assurances to CMS. (a...

Proteomic Analysis of Male-Fertility Restoration in CMS Onion

USDA-ARS?s Scientific Manuscript database

The production of hybrid-onion seed is dependent on cytoplasmic-genic male sterility (CMS) systems. For the most commonly used CMS, male-sterile (S) cytoplasm interacts with a dominant allele at one nuclear male-fertility restoration locus (Ms) to condition male fertility. We are using proteomics ...

78 FR 78970 - Emergency Clearance: Public Information Collection Requirements Submitted to the Office of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-27

... Identifier: CMS-10510] Emergency Clearance: Public Information Collection Requirements Submitted to the Office of Management and Budget (OMB); Correction AGENCY: Centers for Medicare & Medicaid Services (CMS..., Federal Register notice (document identifier: CMS-10510) entitled ``Basic Health Program Report for Health...

45 CFR 150.459 - Judicial review.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS CMS...) Simultaneously sending a copy of the notice of appeal by registered mail to CMS. (b) Certification of administrative record. CMS promptly certifies and files with the court the record upon which the penalty was...