The CMS DBS query language

NASA Astrophysics Data System (ADS)

Kuznetsov, Valentin; Riley, Daniel; Afaq, Anzar; Sekhri, Vijay; Guo, Yuyi; Lueking, Lee

2010-04-01

The CMS experiment has implemented a flexible and powerful system enabling users to find data within the CMS physics data catalog. The Dataset Bookkeeping Service (DBS) comprises a database and the services used to store and access metadata related to CMS physics data. To this, we have added a generalized query system in addition to the existing web and programmatic interfaces to the DBS. This query system is based on a query language that hides the complexity of the underlying database structure by discovering the join conditions between database tables. This provides a way of querying the system that is simple and straightforward for CMS data managers and physicists to use without requiring knowledge of the database tables or keys. The DBS Query Language uses the ANTLR tool to build the input query parser and tokenizer, followed by a query builder that uses a graph representation of the DBS schema to construct the SQL query sent to underlying database. We will describe the design of the query system, provide details of the language components and overview of how this component fits into the overall data discovery system architecture.

Compare ultrasound-mediated heating and cavitation between flowing polymer- and lipid-shelled microbubbles during focused ultrasound exposures.

PubMed

Zhang, Siyuan; Zong, Yujin; Wan, Mingxi; Yu, Xiaojun; Fu, Quanyou; Ding, Ting; Zhou, Fanyu; Wang, Supin

2012-06-01

This paper compares the efficiency of flowing polymer- and lipid-shelled microbubbles (MBs) in the heating and cavitation during focused ultrasound exposures. Temperature and cavitation activity were simultaneously measured as the two types of shelled MBs and saline flowing through a 3 mm diameter vessel in the phantom with varying flow velocities (0-20 cm/s) at different acoustic power levels (0.6-20 W) with each exposure for 5 s. Temperature and cavitation for the lipid-shelled MBs were higher than those for the polymer-shelled MBs. Temperature rise decreased with increasing flow velocities for the two types of shelled MBs and saline at acoustic power 1.5 W. At acoustic power 11.1 W, temperature rise increased with increasing flow velocities for the lipid-shelled MBs. For the polymer-shelled MBs, the temperature rise increased with increasing flow velocities from 3-15 cm/s and decreased at 20 cm/s. Cavitation increased with increasing flow velocity for the two shelled MBs and there were no significant changes of cavitation with increasing flow velocities for saline. These results suggested that lipid-shelled MBs may have a greater efficiency than polymer-shelled MBs in heating and cavitation during focused ultrasound exposures.

Operation and performance of the LHCb calorimeters

NASA Astrophysics Data System (ADS)

Chefdeville, M.

2018-03-01

The LHCb calorimeters play a key role in the hardware trigger of the experiment. They also serve the measurement of radiative heavy flavor decays and the identification of electrons. Located at twelve meters from the interaction region, they are composed of a plane of scintillating tiles, a preshower detector, an electromagnetic and a hadronic sampling calorimeters using scintillators as active elements. In these proceedings, technical and operational aspects of these detectors are described. Emphasis is then put on calorimeter reconstruction and calibration. Finally, performance for benchmark physics modes are briefly reported.

The CMS tracker control system

NASA Astrophysics Data System (ADS)

Dierlamm, A.; Dirkes, G. H.; Fahrer, M.; Frey, M.; Hartmann, F.; Masetti, L.; Militaru, O.; Shah, S. Y.; Stringer, R.; Tsirou, A.

2008-07-01

The Tracker Control System (TCS) is a distributed control software to operate about 2000 power supplies for the silicon modules of the CMS Tracker and monitor its environmental sensors. TCS must thus be able to handle about 104 power supply parameters, about 103 environmental probes from the Programmable Logic Controllers of the Tracker Safety System (TSS), about 105 parameters read via DAQ from the DCUs in all front end hybrids and from CCUs in all control groups. TCS is built on top of an industrial SCADA program (PVSS) extended with a framework developed at CERN (JCOP) and used by all LHC experiments. The logical partitioning of the detector is reflected in the hierarchical structure of the TCS, where commands move down to the individual hardware devices, while states are reported up to the root which is interfaced to the broader CMS control system. The system computes and continuously monitors the mean and maximum values of critical parameters and updates the percentage of currently operating hardware. Automatic procedures switch off selected parts of the detector using detailed granularity and avoiding widespread TSS intervention.

MicroTCA-based Global Trigger Upgrade project for the CMS experiment at LHC

NASA Astrophysics Data System (ADS)

Rahbaran, B.; Arnold, B.; Bergauer, H.; Eichberger, M.; Rabady, D.

2011-12-01

The electronics of the first Level Global Trigger (GT) of CMS is the last stage of the Level-1 trigger system [1]. At LHC up to 40 million collisions of proton bunches occur every second, resulting in about 800 million proton collisions. The CMS Level-1 Global Trigger [1], a custom designed electronics system based on FPGA technology and the VMEbus system, performs a quick on-line analysis of each collision every 25 ns and decides whether to reject or to accept it for further analysis. The CMS trigger group of the Institute of High Energy Physics in Vienna (HEPHY) is involved in the Level-1 trigger of the CMS experiment at CERN. As part of the Trigger Upgrade, the Level-1 Global Trigger will be redesigned and implemented in MicroTCA based technology, which allows engineers to detect all possible faults on plug-in boards, in the power supply and in the cooling system. The upgraded Global Trigger will be designed to have the same basic categories of functions as the present GT, but will have more algorithms and more possibilities for combining trigger candidates. Additionally, reconfigurability and testability will be supported based on the next system generation.

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.

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

Intelligent systems and advanced user interfaces for design, operation, and maintenance of command management systems

NASA Technical Reports Server (NTRS)

Potter, William J.; Mitchell, Christine M.

1993-01-01

Historically, command management systems (CMS) have been large and expensive spacecraft-specific software systems that were costly to build, operate, and maintain. Current and emerging hardware, software, and user interface technologies may offer an opportunity to facilitate the initial formulation and design of a spacecraft-specific CMS as well as to develop a more generic CMS system. New technologies, in addition to a core CMS common to a range of spacecraft, may facilitate the training and enhance the efficiency of CMS operations. Current mission operations center (MOC) hardware and software include Unix workstations, the C/C++ programming languages, and an X window interface. This configuration provides the power and flexibility to support sophisticated and intelligent user interfaces that exploit state-of-the-art technologies in human-machine interaction, artificial intelligence, and software engineering. One of the goals of this research is to explore the extent to which technologies developed in the research laboratory can be productively applied in a complex system such as spacecraft command management. Initial examination of some of these issues in CMS design and operation suggests that application of technologies such as intelligent planning, case-based reasoning, human-machine systems design and analysis tools (e.g., operator and designer models), and human-computer interaction tools (e.g., graphics, visualization, and animation) may provide significant savings in the design, operation, and maintenance of the CMS for a specific spacecraft as well as continuity for CMS design and development across spacecraft. The first six months of this research saw a broad investigation by Georgia Tech researchers into the function, design, and operation of current and planned command management systems at Goddard Space Flight Center. As the first step, the researchers attempted to understand the current and anticipated horizons of command management systems at Goddard. Preliminary results are given on CMS commonalities and causes of low re-use, and methods are proposed to facilitate increased re-use.

Search for gamma-rays above 400 GeV from Geminga

NASA Technical Reports Server (NTRS)

Cawley, M. F.; Fegan, D. J.; Gibbs, K.; Gorham, P. W.; Lamb, R. C.; Liebing, D. F.; Mackeown, P. K.; Porter, N. A.; Stenger, V. J.; Weekes, T. C.

1985-01-01

Observations of Geminga made at the Whipple Observatory using the atmospheric Cherenkov technique during the moonless periods of November 1983 to February 1984 and November 1984 till February 1985 were examined for evidence for the emission of gamma rays with energy in excess of approx 400 GeV. Evidence of either a steady flux or a flux pulsed with a period near 60 seconds were studied. In neither case was any significant effect observed, enabling the establishment 3 of sigma upper limits of 5.5 x 10 to the -11th power photons/sq cm/s and 2.0 x 10 to the -11th power photons/sq cm/s for the steady and pulsed emission respectively. The limit to the pulsed flux is approximately a factor of six below that predicted.

Advantages of Repeated Low Dose against Single High Dose of Kainate in C57BL/6J Mouse Model of Status Epilepticus: Behavioral and Electroencephalographic Studies

PubMed Central

Beamer, Edward; Sills, Graeme J.; Thippeswamy, Thimmasettappa

2014-01-01

A refined kainate (KA) C57BL/6J mouse model of status epilepticus (SE) using a repeated low dose (RLD) of KA (5 mg/kg, intraperitoneal; at 30 min intervals) was compared with the established single high dose (SHD) of KA (20 mg/kg, intraperitoneal) model. In the RLD group, increased duration of convulsive motor seizures (CMS, Racine scale stage ≥3) with a significant reduction in mortality from 21% to 6% and decreased variability in seizure severity between animals/batches were observed when compared to the SHD group. There was a significant increase in the percentage of animals that reached stage-5 seizures (65% versus 96%) in the RLD group. Integrated real-time video-EEG analysis of both groups, using NeuroScore software, revealed stage-specific spikes and power spectral density characteristics. When the seizures progressed from non-convulsive seizures (NCS, stage 1–2) to CMS (stage 3–5), the delta power decreased which was followed by an increase in gamma and beta power. A transient increase in alpha and sigma power marked the transition from NCS to CMS with characteristic ‘high frequency trigger’ spikes on the EEG, which had no behavioral expression. During SE the spike rate was higher in the RLD group than in the SHD group. Overall these results confirm that RLD of KA is a more robust and consistent mouse model of SE than the SHD of KA mouse model. PMID:24802808

Thermal photons in heavy ion collisions at 158 A GeV

NASA Astrophysics Data System (ADS)

Dutt, Sunil

2018-05-01

The essence of experimental ultra-relativistic heavy ion collision physics is the production and study of strongly interacting matter at extreme energy densities, temperatures and consequent search for equation of state of nuclear matter. The focus of the analysis has been to examine pseudo-rapidity distributions obtained for the γ-like particles in pre-shower photon multiplicity detector. This allows the extension of scaled factorial moment analysis to bin sizes smaller than those accessible to other experimental techniques. Scaled factorial moments are calculated using horizontal corrected and vertical analysis. The results are compared with simulation analysis using VENUS event generator.

Fiber Optics at the JLab CLAS12 Detector

NASA Astrophysics Data System (ADS)

Kroon, John; Giovanetti, Kevin

2008-10-01

The performance of wavelength shifting fibers, WLS, and method of coupling these fibers to extruded polystyrene scintillators are currently under study at James Madison University. These components are two of the main elements for the PCAL, preshower calorimeter, proposed as part of the 12 GeV upgrade for the CLAS detector at Jefferson Laboratory. The WLS fibers have been prepared, optically coupled to scintillator, and tested in order to determine their overall performance as a method of readout. Methods of coupling fiber to scintillator, a description of the test setup, test methods, PCAL readout performance, and fabrication recommendations will be presented.

VIPRAM_L1CMS: a 2-Tier 3D Architecture for Pattern Recognition for Track Finding

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

Hoff, J. R.; Joshi, Joshi,S.; Liu, Liu,

In HEP tracking trigger applications, flagging an individual detector hit is not important. Rather, the path of a charged particle through many detector layers is what must be found. Moreover, given the increased luminosity projected for future LHC experiments, this type of track finding will be required within the Level 1 Trigger system. This means that future LHC experiments require not just a chip capable of high-speed track finding but also one with a high-speed readout architecture. VIPRAM_L1CMS is 2-Tier Vertically Integrated chip designed to fulfill these requirements. It is a complete pipelined Pattern Recognition Associative Memory (PRAM) architecture includingmore » pattern recognition, result sparsification, and readout for Level 1 trigger applications in CMS with 15-bit wide detector addresses and eight detector layers included in the track finding. Pattern recognition is based on classic Content Addressable Memories with a Current Race Scheme to reduce timing complexity and a 4-bit Selective Precharge to minimize power consumption. VIPRAM_L1CMS uses a pipelined set of priority-encoded binary readout structures to sparsify and readout active road flags at frequencies of at least 100MHz. VIPRAM_L1CMS is designed to work directly with the Pulsar2b Architecture.« less

Microbial community composition and electricity generation in cattle manure slurry treatment using microbial fuel cells: effects of inoculum addition.

PubMed

Xie, Binghan; Gong, Weijia; Ding, An; Yu, Huarong; Qu, Fangshu; Tang, Xiaobin; Yan, Zhongsen; Li, Guibai; Liang, Heng

2017-10-01

Microbial fuel cell (MFC) is a sustainable technology to treat cattle manure slurry (CMS) for converting chemical energy to bioelectricity. In this work, two types of allochthonous inoculum including activated sludge (AS) and domestic sewage (DS) were added into the MFC systems to enhance anode biofilm formation and electricity generation. Results indicated that MFCs (AS + CMS) obtained the maximum electricity output with voltage approaching 577 ± 7 mV (~ 196 h), followed by MFCs (DS + CMS) (520 ± 21 mV, ~ 236 h) and then MFCs with autochthonous inoculum (429 ± 62 mV, ~ 263.5 h). Though the raw cattle manure slurry (RCMS) could facilitate electricity production in MFCs, the addition of allochthonous inoculum (AS/DS) significantly reduced the startup time and enhanced the output voltage. Moreover, the maximum power (1.259 ± 0.015 W/m 2 ) and the highest COD removal (84.72 ± 0.48%) were obtained in MFCs (AS + CMS). With regard to microbial community, Illumina HiSeq of the 16S rRNA gene was employed in this work and the exoelectrogens (Geobacter and Shewanella) were identified as the dominant members on all anode biofilms in MFCs. For anode microbial diversity, the MFCs (AS + CMS) outperformed MFCs (DS + CMS) and MFCs (RCMS), allowing the occurrence of the fermentative (e.g., Bacteroides) and nitrogen fixation bacteria (e.g., Azoarcus and Sterolibacterium) which enabled the efficient degradation of the slurry. This study provided a feasible strategy to analyze the anode biofilm formation by adding allochthonous inoculum and some implications for quick startup of MFC reactors for CMS treatment.

Power generation using different cation, anion, and ultrafiltration membranes in microbial fuel cells.

PubMed

Kim, Jung Rae; Cheng, Shaoan; Oh, Sang-Eun; Logan, Bruce E

2007-02-01

Proton exchange membranes (PEMs) are often used in microbial fuel cells (MFCs) to separate the liquid in the anode and cathode chambers while allowing protons to pass between the chambers. However, negatively or positively charged species present at high concentrations in the medium can also be used to maintain charge balance during power generation. An anion exchange membrane (AEM) produced the largest power density (up to 610 mW/m2) and Coulombic efficiency (72%) in MFCs relative to values achieved with a commonly used PEM (Nafion), a cation exchange membrane (CEM), or three different ultrafiltration (UF) membranes with molecular weight cut offs of 0.5K, 1K, and 3K Daltons in different types of MFCs. The increased performance of the AEM was due to proton charge-transfer facilitated by phosphate anions and low internal resistance. The type of membrane affected maximum power densities in two-chamber, air-cathode cube MFCs (C-MFCs) with low internal resistance (84-91 omega for all membranes except UF-0.5K) but not in two-chamber aqueous-cathode bottle MFCs (B-MFCs) due to their higher internal resistances (1230-1272 omega except UF-0.5K). The UF-0.5K membrane produced very high internal resistances (6009 omega, B-MFC; 1814omega, C-MFC) and was the least permeable to both oxygen (mass transfer coefficient of k(O) = 0.19 x 10(-4) cm/s) and acetate (k(A) = 0.89 x 10(-8) cm/s). Nafion was the most permeable membrane to oxygen (k(O) = 1.3 x 10(-4) cm/s), and the UF-3K membrane was the most permeable to acetate (k(A) = 7.2 x 10(-8) cm/s). Only a small percent of substrate was unaccounted for based on measured Coulombic efficiencies and estimates of biomass production and substrate losses using Nafion, CEM, and AEM membranes (4-8%), while a substantial portion of substrate was lost to unidentified processes for the UF membranes (40-89%). These results show that many types of membranes can be used in two-chambered MFCs, even membranes that transfer negatively charged species.

Direct In Vivo Reprogramming with Sendai Virus Vectors Improves Cardiac Function after Myocardial Infarction.

PubMed

Miyamoto, Kazutaka; Akiyama, Mizuha; Tamura, Fumiya; Isomi, Mari; Yamakawa, Hiroyuki; Sadahiro, Taketaro; Muraoka, Naoto; Kojima, Hidenori; Haginiwa, Sho; Kurotsu, Shota; Tani, Hidenori; Wang, Li; Qian, Li; Inoue, Makoto; Ide, Yoshinori; Kurokawa, Junko; Yamamoto, Tsunehisa; Seki, Tomohisa; Aeba, Ryo; Yamagishi, Hiroyuki; Fukuda, Keiichi; Ieda, Masaki

2018-01-04

Direct cardiac reprogramming holds great promise for regenerative medicine. We previously generated directly reprogrammed induced cardiomyocyte-like cells (iCMs) by overexpression of Gata4, Mef2c, and Tbx5 (GMT) using retrovirus vectors. However, integrating vectors pose risks associated with insertional mutagenesis and disruption of gene expression and are inefficient. Here, we show that Sendai virus (SeV) vectors expressing cardiac reprogramming factors efficiently and rapidly reprogram both mouse and human fibroblasts into integration-free iCMs via robust transgene expression. SeV-GMT generated 100-fold more beating iCMs than retroviral-GMT and shortened the duration to induce beating cells from 30 to 10 days in mouse fibroblasts. In vivo lineage tracing revealed that the gene transfer of SeV-GMT was more efficient than retroviral-GMT in reprogramming resident cardiac fibroblasts into iCMs in mouse infarct hearts. Moreover, SeV-GMT improved cardiac function and reduced fibrosis after myocardial infarction. Thus, efficient, non-integrating SeV vectors may serve as a powerful system for cardiac regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Exploring forward physics with the PHENIX MPC-EX upgrade

NASA Astrophysics Data System (ADS)

Novitzky, Norbert; Phenix Collaboration

2014-09-01

The MPC-EX detector is a Si-W preshower extension to the existing Muon Piston Calorimeter (MPC) at PHENIX. Located at forward rapidity, 3 . 1 < | η | < 3 . 8 , the MPC-EX consists of eight layers of alternating W absorber and Si minipad sensors. Covering a large range at forward rapidity makes the MPC-EX and MPC ideal to access low-x partons in the A nucleus of p + A collisions. The neutral pion and direct photon are excellent probes to separate between the initial and final state effects of the pA collisions. Isolating the direct photon signal requires the MPC-EX to be able to distinguish single showers from double showers. The single versus double shower separation was tested with an electron beam at the SLAC test beam facility. Results from the test beam data will be presented in this talk. The MPC-EX detector is a Si-W preshower extension to the existing Muon Piston Calorimeter (MPC) at PHENIX. Located at forward rapidity, 3 . 1 < | η | < 3 . 8 , the MPC-EX consists of eight layers of alternating W absorber and Si minipad sensors. Covering a large range at forward rapidity makes the MPC-EX and MPC ideal to access low-x partons in the A nucleus of p + A collisions. The neutral pion and direct photon are excellent probes to separate between the initial and final state effects of the pA collisions. Isolating the direct photon signal requires the MPC-EX to be able to distinguish single showers from double showers. The single versus double shower separation was tested with an electron beam at the SLAC test beam facility. Results from the test beam data will be presented in this talk. Norbert Novitzky for PHENIX collaboration.

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.

Intelligent Systems and Advanced User Interfaces for Design, Operation, and Maintenance of Command Management Systems

NASA Technical Reports Server (NTRS)

Mitchell, Christine M.

1998-01-01

Historically Command Management Systems (CMS) have been large, expensive, spacecraft-specific software systems that were costly to build, operate, and maintain. Current and emerging hardware, software, and user interface technologies may offer an opportunity to facilitate the initial formulation and design of a spacecraft-specific CMS as well as a to develop a more generic or a set of core components for CMS systems. Current MOC (mission operations center) hardware and software include Unix workstations, the C/C++ and Java programming languages, and X and Java window interfaces representations. This configuration provides the power and flexibility to support sophisticated systems and intelligent user interfaces that exploit state-of-the-art technologies in human-machine systems engineering, decision making, artificial intelligence, and software engineering. One of the goals of this research is to explore the extent to which technologies developed in the research laboratory can be productively applied in a complex system such as spacecraft command management. Initial examination of some of the issues in CMS design and operation suggests that application of technologies such as intelligent planning, case-based reasoning, design and analysis tools from a human-machine systems engineering point of view (e.g., operator and designer models) and human-computer interaction tools, (e.g., graphics, visualization, and animation), may provide significant savings in the design, operation, and maintenance of a spacecraft-specific CMS as well as continuity for CMS design and development across spacecraft with varying needs. The savings in this case is in software reuse at all stages of the software engineering process.

Inverse effects of flowing phase-shift nanodroplets and lipid-shelled microbubbles on subsequent cavitation during focused ultrasound exposures.

PubMed

Zhang, Siyuan; Cui, Zhiwei; Xu, Tianqi; Liu, Pan; Li, Dapeng; Shang, Shaoqiang; Xu, Ranxiang; Zong, Yujin; Niu, Gang; Wang, Supin; He, Xijing; Wan, Mingxi

2017-01-01

This paper compared the effects of flowing phase-shift nanodroplets (NDs) and lipid-shelled microbubbles (MBs) on subsequent cavitation during focused ultrasound (FUS) exposures. The cavitation activity was monitored using a passive cavitation detection method as solutions of either phase-shift NDs or lipid-shelled MBs flowed at varying velocities through a 5-mm diameter wall-less vessel in a transparent tissue-mimicking phantom when exposed to FUS. The intensity of cavitation for the phase-shift NDs showed an upward trend with time and cavitation for the lipid-shelled MBs grew to a maximum at the outset of the FUS exposure followed by a trend of decreases when they were static in the vessel. Meanwhile, the increase of cavitation for the phase-shift NDs and decrease of cavitation for the lipid-shelled MBs had slowed down when they flowed through the vessel. During two discrete identical FUS exposures, while the normalized inertial cavitation dose (ICD) value for the lipid-shelled MB solution was higher than that for the saline in the first exposure (p-value <0.05), it decreased to almost the same level in the second exposure. For the phase-shift NDs, the normalized ICD was 0.71 in the first exposure and increased to 0.97 in the second exposure. At a low acoustic power, the normalized ICD values for the lipid-shelled MBs tended to increase with increasing velocities from 5 to 30cm/s (r>0.95). Meanwhile, the normalized ICD value for the phase-shift NDs was 0.182 at a flow velocity of 5cm/s and increased to 0.188 at a flow velocity of 15cm/s. As the flow velocity increased to 20cm/s, the normalized ICD was 0.185 and decreased to 0.178 at a flow velocity of 30cm/s. At high acoustic power, the normalized ICD values for both the lipid-shelled MBs and the phase-shift NDs increased with increasing flow velocities from 5 to 30cm/s (r>0.95). The effects of the flowing phase-shift NDs vaporized into gas bubbles as cavitation nuclei on the subsequent cavitation were inverse to those of the flowing lipid-shelled MBs destroyed after focused ultrasound exposures. Copyright © 2016 Elsevier B.V. All rights reserved.

An Integrated Environment Monitoring System for Underground Coal Mines—Wireless Sensor Network Subsystem with Multi-Parameter Monitoring

PubMed Central

Zhang, Yu; Yang, Wei; Han, Dongsheng; Kim, Young-Il

2014-01-01

Environment monitoring is important for the safety of underground coal mine production, and it is also an important application of Wireless Sensor Networks (WSNs). We put forward an integrated environment monitoring system for underground coal mine, which uses the existing Cable Monitoring System (CMS) as the main body and the WSN with multi-parameter monitoring as the supplementary technique. As CMS techniques are mature, this paper mainly focuses on the WSN and the interconnection between the WSN and the CMS. In order to implement the WSN for underground coal mines, two work modes are designed: periodic inspection and interrupt service; the relevant supporting technologies, such as routing mechanism, collision avoidance, data aggregation, interconnection with the CMS, etc., are proposed and analyzed. As WSN nodes are limited in energy supply, calculation and processing power, an integrated network management scheme is designed in four aspects, i.e., topology management, location management, energy management and fault management. Experiments were carried out both in a laboratory and in a real underground coal mine. The test results indicate that the proposed integrated environment monitoring system for underground coal mines is feasible and all designs performed well as expected. PMID:25051037

Assessment of diastolic function by tissue Doppler echocardiography: comparison with standard transmitral and pulmonary venous flow

NASA Technical Reports Server (NTRS)

Farias, C. A.; Rodriguez, L.; Garcia, M. J.; Sun, J. P.; Klein, A. L.; Thomas, J. D.

1999-01-01

The objective of this study was to determine the utility of Doppler tissue echocardiography in the evaluation of diastolic filling and in discriminating between normal subjects and those with various stages of diastolic dysfunction. We measured myocardial velocities in 51 patients with various stages of diastolic dysfunction and in 27 normal volunteers. The discriminating power of each of the standard Doppler indexes of left ventricular filling, pulmonary venous flow, and myocardial velocities was determined with the use of Spearman rank correlation and analysis of variance F statistics. Early diastolic myocardial velocity (E(m)) was higher in normal subjects (16.0 +/- 3.8 cm/s) than in patients with either delayed relaxation (n = 15, 7.5 +/- 2.2 cm/s), pseudonormal filling (n = 26, 7.6 +/- 2.3 cm/s), or restrictive filling (n = 10, 7.4 +/- 2.4 cm/s, P <.0001). E(m ) was the best single discriminator between control subjects and patients with diastolic dysfunction (P =.7, F = 64.5). Myocardial velocities assessed by Doppler tissue echocardiography are useful in differentiating patients with normal from those with abnormal diastolic function. Myocardial velocity remains reduced even in those stages of diastolic dysfunction characterized by increased preload compensation.

One lens missing? Clarifying the clinical microsystem framework with learning theories.

PubMed

Norman, Ann-Charlott; Fritzen, Lena; Fridh, Marianne Lindblad

2013-01-01

The clinical microsystem (CMS) approach is widely used and is perceived as helpful in practice but, we ask the question: "Is its learning potential sufficiently utilized?" To scrutinize aspects of learning within the CMS framework and to clarify the learning aspects the framework includes and thereby support the framework with the enhanced learning perspective that becomes visible. Literature on the CMS framework was systematically searched and selected using inclusion criteria. An analytical tool was constructed in the form of a theoretical lens that was used to clarify learning aspects that are associated with the framework. The analysis revealed 3 learning aspects: (1) The CMS framework describes individual and social learning but not how to adapt learning strategies for purposes of change. (2) The metaphorical language of how to reach a holistic health care system for each patient has developed over time but can still be improved by naming social interactions to transcend organizational boundaries. (3) Power structures are recognized but not as a characteristic that restricts learning due to asymmetric communication. The "lens" perspective reveals new meanings to learning that enhance our understanding of health care as a social system and provides new practical learning strategies.

L1 track trigger for the CMS HL-LHC upgrade using AM chips and FPGAs

NASA Astrophysics Data System (ADS)

Fedi, Giacomo

2017-08-01

The increase of luminosity at the HL-LHC will require the introduction of tracker information in CMS's Level-1 trigger system to maintain an acceptable trigger rate when selecting interesting events, despite the order of magnitude increase in minimum bias interactions. To meet the latency requirements, dedicated hardware has to be used. This paper presents the results of tests of a prototype system (pattern recognition ezzanine) as core of pattern recognition and track fitting for the CMS experiment, combining the power of both associative memory custom ASICs and modern Field Programmable Gate Array (FPGA) devices. The mezzanine uses the latest available associative memory devices (AM06) and the most modern Xilinx Ultrascale FPGAs. The results of the test for a complete tower comprising about 0.5 million patterns is presented, using as simulated input events traversing the upgraded CMS detector. The paper shows the performance of the pattern matching, track finding and track fitting, along with the latency and processing time needed. The pT resolution over pT of the muons measured using the reconstruction algorithm is at the order of 1% in the range 3-100 GeV/c.

An integrated environment monitoring system for underground coal mines--Wireless Sensor Network subsystem with multi-parameter monitoring.

PubMed

Zhang, Yu; Yang, Wei; Han, Dongsheng; Kim, Young-Il

2014-07-21

Environment monitoring is important for the safety of underground coal mine production, and it is also an important application of Wireless Sensor Networks (WSNs). We put forward an integrated environment monitoring system for underground coal mine, which uses the existing Cable Monitoring System (CMS) as the main body and the WSN with multi-parameter monitoring as the supplementary technique. As CMS techniques are mature, this paper mainly focuses on the WSN and the interconnection between the WSN and the CMS. In order to implement the WSN for underground coal mines, two work modes are designed: periodic inspection and interrupt service; the relevant supporting technologies, such as routing mechanism, collision avoidance, data aggregation, interconnection with the CMS, etc., are proposed and analyzed. As WSN nodes are limited in energy supply, calculation and processing power, an integrated network management scheme is designed in four aspects, i.e., topology management, location management, energy management and fault management. Experiments were carried out both in a laboratory and in a real underground coal mine. The test results indicate that the proposed integrated environment monitoring system for underground coal mines is feasible and all designs performed well as expected.

Theory of compressive modeling and simulation

NASA Astrophysics Data System (ADS)

Szu, Harold; Cha, Jae; Espinola, Richard L.; Krapels, Keith

2013-05-01

Modeling and Simulation (M&S) has been evolving along two general directions: (i) data-rich approach suffering the curse of dimensionality and (ii) equation-rich approach suffering computing power and turnaround time. We suggest a third approach. We call it (iii) compressive M&S (CM&S); because the basic Minimum Free-Helmholtz Energy (MFE) facilitating CM&S can reproduce and generalize Candes, Romberg, Tao & Donoho (CRT&D) Compressive Sensing (CS) paradigm as a linear Lagrange Constraint Neural network (LCNN) algorithm. CM&S based MFE can generalize LCNN to 2nd order as Nonlinear augmented LCNN. For example, during the sunset, we can avoid a reddish bias of sunlight illumination due to a long-range Rayleigh scattering over the horizon. With CM&S we can take instead of day camera, a night vision camera. We decomposed long wave infrared (LWIR) band with filter into 2 vector components (8~10μm and 10~12μm) and used LCNN to find pixel by pixel the map of Emissive-Equivalent Planck Radiation Sources (EPRS). Then, we up-shifted consistently, according to de-mixed sources map, to the sub-micron RGB color image. Moreover, the night vision imaging can also be down-shifted at Passive Millimeter Wave (PMMW) imaging, suffering less blur owing to dusty smokes scattering and enjoying apparent smoothness of surface reflectivity of man-made objects under the Rayleigh resolution. One loses three orders of magnitudes in the spatial Rayleigh resolution; but gains two orders of magnitude in the reflectivity, and gains another two orders in the propagation without obscuring smog . Since CM&S can generate missing data and hard to get dynamic transients, CM&S can reduce unnecessary measurements and their associated cost and computing in the sense of super-saving CS: measuring one & getting one's neighborhood free .

Course Management Systems: Traveling Beyond Powerpoint Slides Online

NASA Astrophysics Data System (ADS)

Gauthier, A. J.; Impey, C. D.

2004-12-01

Course management systems (CMS) like WebCT, Blackboard, Astronomica, etc., have reached and surpassed their tipping point in higher education. They are no longer a technology-trendy item to use in a course, but rather an expected supplement to undergraduate courses. There is a well known disconnect between the student population of ''digital natives'' (1) and higher education instructors, the ''digital immigrants'' (1). What expectations and technology skills do the new generations of undergraduates have? How can instructors easily meet their students' needs? What needs do instructors have and what resources are available to meet those needs? In the past, instructors would create their own HTML web pages to post class materials like PowerPoint slides, homework, and announcements. How does an instructor-created web resource differ from a secure university run CMS? How can you make your university or college's CMS system into a productive learning tool and not just a repository for class materials and grades? How can the astronomy instructor benefit from integrating a CMS into their course? What are common student attitudes regarding CMS usage in a course? How are instructors using CMSs in innovative ways? Where on your campus can you get free help designing and implementing a CMS resource for your students? This presentation aims to answer these questions. Extensive literature reviews, formal surveys, case study reports, and educational research from the instructional technology community inform our astronomy teaching community of the answers. Highlights from innovative systems and uses of CMSs in undergraduate Astro 101 classrooms will be presented. Resources and further references will be made available as handouts. (1) M. Prensky. ''Digital Natives, Digital Immigrants,'' On The Horizon, Vol.9, 2001.

A browser-based event display for the CMS Experiment at the LHC using WebGL

NASA Astrophysics Data System (ADS)

McCauley, T.

2017-10-01

Modern web browsers are powerful and sophisticated applications that support an ever-wider range of uses. One such use is rendering high-quality, GPU-accelerated, interactive 2D and 3D graphics in an HTML canvas. This can be done via WebGL, a JavaScript API based on OpenGL ES. Applications delivered via the browser have several distinct benefits for the developer and user. For example, they can be implemented using well-known and well-developed technologies, while distribution and use via a browser allows for rapid prototyping and deployment and ease of installation. In addition, delivery of applications via the browser allows for easy use on mobile, touch-enabled devices such as phones and tablets. iSpy WebGL is an application for visualization of events detected and reconstructed by the CMS Experiment at the Large Hadron Collider at CERN. The first event display developed for an LHC experiment to use WebGL, iSpy WebGL is a client-side application written in JavaScript, HTML, and CSS and uses the WebGL API three.js. iSpy WebGL is used for monitoring of CMS detector performance, for production of images and animations of CMS collisions events for the public, as a virtual reality application using Google Cardboard, and asa tool available for public education and outreach such as in the CERN Open Data Portal and the CMS masterclasses. We describe here its design, development, and usage as well as future plans.

Trends in non-stationary signal processing techniques applied to vibration analysis of wind turbine drive train - A contemporary survey

NASA Astrophysics Data System (ADS)

Uma Maheswari, R.; Umamaheswari, R.

2017-02-01

Condition Monitoring System (CMS) substantiates potential economic benefits and enables prognostic maintenance in wind turbine-generator failure prevention. Vibration Monitoring and Analysis is a powerful tool in drive train CMS, which enables the early detection of impending failure/damage. In variable speed drives such as wind turbine-generator drive trains, the vibration signal acquired is of non-stationary and non-linear. The traditional stationary signal processing techniques are inefficient to diagnose the machine faults in time varying conditions. The current research trend in CMS for drive-train focuses on developing/improving non-linear, non-stationary feature extraction and fault classification algorithms to improve fault detection/prediction sensitivity and selectivity and thereby reducing the misdetection and false alarm rates. In literature, review of stationary signal processing algorithms employed in vibration analysis is done at great extent. In this paper, an attempt is made to review the recent research advances in non-linear non-stationary signal processing algorithms particularly suited for variable speed wind turbines.

Test beam performance measurements for the Phase I upgrade of the CMS pixel detector

NASA Astrophysics Data System (ADS)

Dragicevic, M.; Friedl, M.; Hrubec, J.; Steininger, H.; Gädda, A.; Härkönen, J.; Lampén, T.; Luukka, P.; Peltola, T.; Tuominen, E.; Tuovinen, E.; Winkler, A.; Eerola, P.; Tuuva, T.; Baulieu, G.; Boudoul, G.; Caponetto, L.; Combaret, C.; Contardo, D.; Dupasquier, T.; Gallbit, G.; Lumb, N.; Mirabito, L.; Perries, S.; Vander Donckt, M.; Viret, S.; Bonnin, C.; Charles, L.; Gross, L.; Hosselet, J.; Tromson, D.; Feld, L.; Karpinski, W.; Klein, K.; Lipinski, M.; Pierschel, G.; Preuten, M.; Rauch, M.; Wlochal, M.; Aldaya, M.; Asawatangtrakuldee, C.; Beernaert, K.; Bertsche, D.; Contreras-Campana, C.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Gallo, E.; Garay Garcia, J.; Hansen, K.; Haranko, M.; Harb, A.; Hauk, J.; Keaveney, J.; Kalogeropoulos, A.; Kleinwort, C.; Lohmann, W.; Mankel, R.; Maser, H.; Mittag, G.; Muhl, C.; Mussgiller, A.; Pitzl, D.; Reichelt, O.; Savitskyi, M.; Schütze, P.; Sola, V.; Spannagel, S.; Walsh, R.; Zuber, A.; Biskop, H.; Buhmann, P.; Centis-Vignali, M.; Garutti, E.; Haller, J.; Hoffmann, M.; Klanner, R.; Lapsien, T.; Matysek, M.; Perieanu, A.; Scharf, Ch.; Schleper, P.; Schmidt, A.; Schwandt, J.; Sonneveld, J.; Steinbrück, G.; Vormwald, B.; Wellhausen, J.; Abbas, M.; Amstutz, C.; Barvich, T.; Barth, Ch.; Boegelspacher, F.; De Boer, W.; Butz, E.; Casele, M.; Colombo, F.; Dierlamm, A.; Freund, B.; Hartmann, F.; Heindl, S.; Husemann, U.; Kornmeyer, A.; Kudella, S.; Muller, Th.; Simonis, H. J.; Steck, P.; Weber, M.; Weiler, Th.; Kiss, T.; Siklér, F.; Tölyhi, T.; Veszprémi, V.; Cariola, P.; Creanza, D.; De Palma, M.; De Robertis, G.; Fiore, L.; Franco, M.; Loddo, F.; Sala, G.; Silvestris, L.; Maggi, G.; My, S.; Selvaggi, G.; Albergo, S.; Cappello, G.; Costa, S.; Di Mattia, A.; Giordano, F.; Potenza, R.; Saizu, M. A.; Tricomi, A.; Tuve, C.; Focardi, E.; Dinardo, M. E.; Fiorendi, S.; Gennai, S.; Malvezzi, S.; Manzoni, R. A.; Menasce, D.; Moroni, L.; Pedrini, D.; Azzi, P.; Bacchetta, N.; Bisello, D.; Dall'Osso, M.; Pozzobon, N.; Tosi, M.; Alunni Solestizi, L.; Biasini, M.; Bilei, G. M.; Cecchi, C.; Checcucci, B.; Ciangottini, D.; Fanò, L.; Gentsos, C.; Ionica, M.; Leonardi, R.; Manoni, E.; Mantovani, G.; Marconi, S.; Mariani, V.; Menichelli, M.; Modak, A.; Morozzi, A.; Moscatelli, F.; Passeri, D.; Placidi, P.; Postolache, V.; Rossi, A.; Saha, A.; Santocchia, A.; Storchi, L.; Spiga, D.; Androsov, K.; Azzurri, P.; Bagliesi, G.; Basti, A.; Boccali, T.; Borrello, L.; Bosi, F.; Castaldi, R.; Ceccanti, M.; Ciocci, M. A.; Dell'Orso, R.; Donato, S.; Fedi, G.; Giassi, A.; Grippo, M. T.; Ligabue, F.; Magazzu, G.; Mammini, P.; Mariani, F.; Mazzoni, E.; Messineo, A.; Moggi, A.; Morsani, F.; Palla, F.; Palmonari, F.; Profeti, A.; Raffaelli, F.; Ragonesi, A.; Rizzi, A.; Soldani, A.; Spagnolo, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Abbaneo, D.; Ahmed, I.; Albert, E.; Auzinger, G.; Berruti, G.; Bonnaud, J.; Daguin, J.; D'Auria, A.; Detraz, S.; Dondelewski, O.; Engegaard, B.; Faccio, F.; Frank, N.; Gill, K.; Honma, A.; Kornmayer, A.; Labaza, A.; Manolescu, F.; McGill, I.; Mersi, S.; Michelis, S.; Onnela, A.; Ostrega, M.; Pavis, S.; Peisert, A.; Pernot, J.-F.; Petagna, P.; Postema, H.; Rapacz, K.; Sigaud, C.; Tropea, P.; Troska, J.; Tsirou, A.; Vasey, F.; Verlaat, B.; Vichoudis, P.; Zwalinski, L.; Bachmair, F.; Becker, R.; di Calafiori, D.; Casal, B.; Berger, P.; Djambazov, L.; Donega, M.; Grab, C.; Hits, D.; Hoss, J.; Kasieczka, G.; Lustermann, W.; Mangano, B.; Marionneau, M.; Martinez Ruiz del Arbol, P.; Masciovecchio, M.; Meinhard, M.; Perozzi, L.; Roeser, U.; Starodumov, A.; Tavolaro, V.; Wallny, R.; Zhu, D.; Amsler, C.; Bösiger, K.; Caminada, L.; Canelli, F.; Chiochia, V.; de Cosa, A.; Galloni, C.; Hreus, T.; Kilminster, B.; Lange, C.; Maier, R.; Ngadiuba, J.; Pinna, D.; Robmann, P.; Taroni, S.; Yang, Y.; Bertl, W.; Deiters, K.; Erdmann, W.; Horisberger, R.; Kaestli, H.-C.; Kotlinski, D.; Langenegger, U.; Meier, B.; Rohe, T.; Streuli, S.; Chen, P.-H.; Dietz, C.; Fiori, F.; Grundler, U.; Hou, W.-S.; Lu, R.-S.; Moya, M.; Tsai, J.-F.; Tzeng, Y. M.; Cussans, D.; Goldstein, J.; Grimes, M.; Newbold, D.; Hobson, P.; Reid, I. D.; Auzinger, G.; Bainbridge, R.; Dauncey, P.; Hall, G.; James, T.; Magnan, A.-M.; Pesaresi, M.; Raymond, D. M.; Uchida, K.; Durkin, T.; Harder, K.; Shepherd-Themistocleous, C.; Chertok, M.; Conway, J.; Conway, R.; Flores, C.; Lander, R.; Pellett, D.; Ricci-Tam, F.; Squires, M.; Thomson, J.; Yohay, R.; Burt, K.; Ellison, J.; Hanson, G.; Olmedo, M.; Si, W.; Yates, B. R.; Dominguez, A.; Bartek, R.; Bentele, B.; Cumalat, J. P.; Ford, W. T.; Jensen, F.; Johnson, A.; Krohn, M.; Leontsinis, S.; Mulholland, T.; Stenson, K.; Wagner, S. R.; Apresyan, A.; Bolla, G.; Burkett, K.; Butler, J. N.; Canepa, A.; Cheung, H. W. K.; Christian, D.; Cooper, W. E.; Deptuch, G.; Derylo, G.; Gingu, C.; Grünendahl, S.; Hasegawa, S.; Hoff, J.; Howell, J.; Hrycyk, M.; Jindariani, S.; Johnson, M.; Kahlid, F.; Kwan, S.; Lei, C. M.; Lipton, R.; Lopes De Sá, R.; Liu, T.; Los, S.; Matulik, M.; Merkel, P.; Nahn, S.; Prosser, A.; Rivera, R.; Schneider, B.; Sellberg, G.; Shenai, A.; Siehl, K.; Spiegel, L.; Tran, N.; Uplegger, L.; Voirin, E.; Berry, D. R.; Chen, X.; Ennesser, L.; Evdokimov, A.; Gerber, C. E.; Makauda, S.; Mills, C.; Sandoval Gonzalez, I. D.; Alimena, J.; Antonelli, L. J.; Francis, B.; Hart, A.; Hill, C. S.; Parashar, N.; Stupak, J.; Bortoletto, D.; Bubna, M.; Hinton, N.; Jones, M.; Miller, D. H.; Shi, X.; Baringer, P.; Bean, A.; Khalil, S.; Kropivnitskaya, A.; Majumder, D.; Schmitz, E.; Wilson, G.; Ivanov, A.; Mendis, R.; Mitchell, T.; Skhirtladze, N.; Taylor, R.; Anderson, I.; Fehling, D.; Gritsan, A.; Maksimovic, P.; Martin, C.; Nash, K.; Osherson, M.; Swartz, M.; Xiao, M.; Acosta, J. G.; Cremaldi, L. M.; Oliveros, S.; Perera, L.; Summers, D.; Bloom, K.; Claes, D. R.; Fangmeier, C.; Gonzalez Suarez, R.; Monroy, J.; Siado, J.; Bartz, E.; Gershtein, Y.; Halkiadakis, E.; Kyriacou, S.; Lath, A.; Nash, K.; Osherson, M.; Schnetzer, S.; Stone, R.; Walker, M.; Malik, S.; Norberg, S.; Ramirez Vargas, J. E.; Alyari, M.; Dolen, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Kharchilava, A.; Nguyen, D.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alexander, J.; Chaves, J.; Chu, J.; Dittmer, S.; McDermott, K.; Mirman, N.; Rinkevicius, A.; Ryd, A.; Salvati, E.; Skinnari, L.; Soffi, L.; Tao, Z.; Thom, J.; Tucker, J.; Zientek, M.; Akgün, B.; Ecklund, K. M.; Kilpatrick, M.; Nussbaum, T.; Zabel, J.; D'Angelo, P.; Johns, W.; Rose, K.; Choudhury, S.; Korol, I.; Seitz, C.; Vargas Trevino, A.; Dolinska, G.

2017-05-01

A new pixel detector for the CMS experiment was built in order to cope with the instantaneous luminosities anticipated for the Phase I Upgrade of the LHC . The new CMS pixel detector provides four-hit tracking with a reduced material budget as well as new cooling and powering schemes. A new front-end readout chip mitigates buffering and bandwidth limitations, and allows operation at low comparator thresholds. In this paper, comprehensive test beam studies are presented, which have been conducted to verify the design and to quantify the performance of the new detector assemblies in terms of tracking efficiency and spatial resolution. Under optimal conditions, the tracking efficiency is 99.95 ± 0.05%, while the intrinsic spatial resolutions are 4.80 ± 0.25 μm and 7.99 ± 0.21 μm along the 100 μm and 150 μm pixel pitch, respectively. The findings are compared to a detailed Monte Carlo simulation of the pixel detector and good agreement is found.

Studying Cold Nuclear Matter with the MPC-EX of PHENIX

NASA Astrophysics Data System (ADS)

Grau, Nathan; Phenix Collaboration

2017-09-01

Highly asymmetric collision systems, such as d+Au, provide a unique environment to study cold nuclear matter. Potential measurements range from pinning down the modification of the nuclear wave function, i.e. saturation, to studying final state interactions, i.e. energy loss. The PHENIX experiment has enhanced the muon piston calorimeter (MPC) with a silicon-tungsten preshower, the MPC-EX. With its fine segmentation the MPC-EX extends the photon detection capability at 3 < | η | < 3.8. In this talk we review the current status of the detector, its calibration, and its identification capabilities using the 2016 d+Au dataset. We also discuss the specific physics observables the MPC-EX can measure.

Engineered heart tissues and induced pluripotent stem cells: Macro- and microstructures for disease modeling, drug screening, and translational studies.

PubMed

Tzatzalos, Evangeline; Abilez, Oscar J; Shukla, Praveen; Wu, Joseph C

2016-01-15

Engineered heart tissue has emerged as a personalized platform for drug screening. With the advent of induced pluripotent stem cell (iPSC) technology, patient-specific stem cells can be developed and expanded into an indefinite source of cells. Subsequent developments in cardiovascular biology have led to efficient differentiation of cardiomyocytes, the force-producing cells of the heart. iPSC-derived cardiomyocytes (iPSC-CMs) have provided potentially limitless quantities of well-characterized, healthy, and disease-specific CMs, which in turn has enabled and driven the generation and scale-up of human physiological and disease-relevant engineered heart tissues. The combined technologies of engineered heart tissue and iPSC-CMs are being used to study diseases and to test drugs, and in the process, have advanced the field of cardiovascular tissue engineering into the field of precision medicine. In this review, we will discuss current developments in engineered heart tissue, including iPSC-CMs as a novel cell source. We examine new research directions that have improved the function of engineered heart tissue by using mechanical or electrical conditioning or the incorporation of non-cardiomyocyte stromal cells. Finally, we discuss how engineered heart tissue can evolve into a powerful tool for therapeutic drug testing. Copyright © 2015 Elsevier B.V. All rights reserved.

Carbon Molecular Sieve Membrane as a True One Box Unit for Large Scale Hydrogen Production

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

Liu, Paul

2012-05-01

IGCC coal-fired power plants show promise for environmentally-benign power generation. In these plants coal is gasified to syngas then processed in a water gas-shift (WGS) reactor to maximize the hydrogen/CO{sub 2} content. The gas stream can then be separated into a hydrogen rich stream for power generation and/or further purified for sale as a chemical and a CO{sub 2} rich stream for the purpose of carbon capture and storage (CCS). Today, the separation is accomplished using conventional absorption/desorption processes with post CO{sub 2} compression. However, significant process complexity and energy penalties accrue with this approach, accounting for ~20% of themore » capital cost and ~27% parasitic energy consumption. Ideally, a one-box process is preferred in which the syngas is fed directly to the WGS reactor without gas pre-treatment, converting the CO to hydrogen in the presence of H{sub 2}S and other impurities and delivering a clean hydrogen product for power generation or other uses. The development of such a process is the primary goal of this project. Our proposed "one-box" process includes a catalytic membrane reactor (MR) that makes use of a hydrogen-selective, carbon molecular sieve (CMS) membrane, and a sulfur-tolerant Co/Mo/Al{sub 2}O{sub 3} catalyst. The membrane reactor's behavior has been investigated with a bench top unit for different experimental conditions and compared with the modeling results. The model is used to further investigate the design features of the proposed process. CO conversion >99% and hydrogen recovery >90% are feasible under the operating pressures available from IGCC. More importantly, the CMS membrane has demonstrated excellent selectivity for hydrogen over H{sub 2}S (>100), and shown no flux loss in the presence of a synthetic "tar"-like material, i.e., naphthalene. In summary, the proposed "one-box" process has been successfully demonstrated with the bench-top reactor. In parallel we have successfully designed and fabricated a full-scale CMS membrane and module for the proposed application. This full-scale membrane element is a 3" diameter with 30"L, composed of ~85 single CMS membrane tubes. The membrane tubes and bundles have demonstrated satisfactory thermal, hydrothermal, thermal cycling and chemical stabilities under an environment simulating the temperature, pressure and contaminant levels encountered in our proposed process. More importantly, the membrane module packed with the CMS bundle was tested for over 30 pressure cycles between ambient pressure and >300 -600 psi at 200 to 300°C without mechanical degradation. Finally, internal baffles have been designed and installed to improve flow distribution within the module, which delivered 90% separation efficiency in comparison with the efficiency achieved with single membrane tubes. In summary, the full-scale CMS membrane element and module have been successfully developed and tested satisfactorily for our proposed one-box application; a test quantity of elements/modules have been fabricated for field testing. Multiple field tests have been performed under this project at National Carbon Capture Center (NCCC). The separation efficiency and performance stability of our full-scale membrane elements have been verified in testing conducted for times ranging from 100 to >250 hours of continuous exposure to coal/biomass gasifier off-gas for hydrogen enrichment with no gas pre-treatment for contaminants removal. In particular, "tar-like" contaminants were effectively rejected by the membrane with no evidence of fouling. In addition, testing was conducted using a hybrid membrane system, i.e., the CMS membrane in conjunction with the palladium membrane, to demonstrate that 99+% H{sub 2} purity and a high degree of CO{sub 2} capture could be achieved. In summary, the stability and performance of the full-scale hydrogen selective CMS membrane/module has been verified in multiple field tests in the presence of coal/biomass gasifier off-gas under this project. A promising process scheme has been developed for power generation and/or hydrogen coproduction with CCS based upon our proposed "one-box" process. Our preliminary economic analysis indicates about 10% reduction in the required electricity selling price and ~40% cost reduction in CCS on per ton CO{sub 2} can be achieved in comparison with the base case involving conventional WGS with a two-stage Selexsol® for CCS. Long term field tests (e.g., >1,000 hrs) with the incorporation of the catalyst for the WGS membrane reactor and more in-depth analysis of the process scheme are recommended for the future study.« less

Advanced power analysis methodology targeted to the optimization of a digital pixel readout chip design and its critical serial powering system

NASA Astrophysics Data System (ADS)

Marconi, S.; Orfanelli, S.; Karagounis, M.; Hemperek, T.; Christiansen, J.; Placidi, P.

2017-02-01

A dedicated power analysis methodology, based on modern digital design tools and integrated with the VEPIX53 simulation framework developed within RD53 collaboration, is being used to guide vital choices for the design and optimization of the next generation ATLAS and CMS pixel chips and their critical serial powering circuit (shunt-LDO). Power consumption is studied at different stages of the design flow under different operating conditions. Significant effort is put into extensive investigations of dynamic power variations in relation with the decoupling seen by the powering network. Shunt-LDO simulations are also reported to prove the reliability at the system level.

All sky Northern Hemisphere 10(15) EV gamma-ray survey

NASA Technical Reports Server (NTRS)

Baltrusaitis, R. M.; Cassiday, G. L.; Cooper, R.; Elbert, J. W.; Gerhardy, P. R.; Loh, E. C.; Mizumoto, Y.; Sokolsky, P.; Sommers, P.; Steck, D.

1985-01-01

Flux limits in the range 10 to the minus 13th power-10 to the minus 12 power/sq cm/s have been obtained by observing Cerenkov flashes from small air showers. During 1983, a 3.5 sigma excess of showers was observed during the phase interval 0.2 to 0.3 of the 4.8h period of Cygnus X-3, but no excess was found in 1984 observations.

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.

Efficient Generation of Human Embryonic Stem Cell-Derived Cardiac Progenitors Based on Tissue-Specific Enhanced Green Fluorescence Protein Expression

PubMed Central

Szebényi, Kornélia; Péntek, Adrienn; Erdei, Zsuzsa; Várady, György; Orbán, Tamás I.; Sarkadi, Balázs

2015-01-01

Cardiac progenitor cells (CPCs) are committed to the cardiac lineage but retain their proliferative capacity before becoming quiescent mature cardiomyocytes (CMs). In medical therapy and research, the use of human pluripotent stem cell-derived CPCs would have several advantages compared with mature CMs, as the progenitors show better engraftment into existing heart tissues, and provide unique potential for cardiovascular developmental as well as for pharmacological studies. Here, we demonstrate that the CAG promoter-driven enhanced green fluorescence protein (EGFP) reporter system enables the identification and isolation of embryonic stem cell-derived CPCs. Tracing of CPCs during differentiation confirmed up-regulation of surface markers, previously described to identify cardiac precursors and early CMs. Isolated CPCs express cardiac lineage-specific transcripts, still have proliferating capacity, and can be re-aggregated into embryoid body-like structures (CAG-EGFPhigh rEBs). Expression of troponin T and NKX2.5 mRNA is up-regulated in long-term cultured CAG-EGFPhigh rEBs, in which more than 90% of the cells become Troponin I positive mature CMs. Moreover, about one third of the CAG-EGFPhigh rEBs show spontaneous contractions. The method described here provides a powerful tool to generate expandable cultures of pure human CPCs that can be used for exploring early markers of the cardiac lineage, as well as for drug screening or tissue engineering applications. PMID:24734786

Understanding the haling power depletion (HPD) method

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

Levine, S.; Blyth, T.; Ivanov, K.

2012-07-01

The Pennsylvania State Univ. (PSU) is using the university version of the Studsvik Scandpower Code System (CMS) for research and education purposes. Preparations have been made to incorporate the CMS into the PSU Nuclear Engineering graduate class 'Nuclear Fuel Management' course. The information presented in this paper was developed during the preparation of the material for the course. The Haling Power Depletion (HPD) was presented in the course for the first time. The HPD method has been criticized as not valid by many in the field even though it has been successfully applied at PSU for the past 20 years.more » It was noticed that the radial power distribution (RPD) for low leakage cores during depletion remained similar to that of the HPD during most of the cycle. Thus, the Haling Power Depletion (HPD) may be used conveniently mainly for low leakage cores. Studies were then made to better understand the HPD and the results are presented in this paper. Many different core configurations can be computed quickly with the HPD without using Burnable Poisons (BP) to produce several excellent low leakage core configurations that are viable for power production. Once the HPD core configuration is chosen for further analysis, techniques are available for establishing the BP design to prevent violating any of the safety constraints in such HPD calculated cores. In summary, in this paper it has been shown that the HPD method can be used for guiding the design for the low leakage core. (authors)« less

Test beam performance measurements for the Phase I upgrade of the CMS pixel detector

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

Dragicevic, M.; Friedl, M.; Hrubec, J.

A new pixel detector for the CMS experiment was built in order to cope with the instantaneous luminosities anticipated for the Phase~I Upgrade of the LHC. The new CMS pixel detector provides four-hit tracking with a reduced material budget as well as new cooling and powering schemes. A new front-end readout chip mitigates buffering and bandwidth limitations, and allows operation at low comparator thresholds. Here in this paper, comprehensive test beam studies are presented, which have been conducted to verify the design and to quantify the performance of the new detector assemblies in terms of tracking efficiency and spatial resolution. Under optimal conditions, the tracking efficiency ismore » $$99.95\\pm0.05\\,\\%$$, while the intrinsic spatial resolutions are $$4.80\\pm0.25\\,\\mu \\mathrm{m}$$ and $$7.99\\pm0.21\\,\\mu \\mathrm{m}$$ along the $$100\\,\\mu \\mathrm{m}$$ and $$150\\,\\mu \\mathrm{m}$$ pixel pitch, respectively. The findings are compared to a detailed Monte Carlo simulation of the pixel detector and good agreement is found.« less

Test beam performance measurements for the Phase I upgrade of the CMS pixel detector

DOE PAGES

Dragicevic, M.; Friedl, M.; Hrubec, J.; ...

2017-05-30

A new pixel detector for the CMS experiment was built in order to cope with the instantaneous luminosities anticipated for the Phase~I Upgrade of the LHC. The new CMS pixel detector provides four-hit tracking with a reduced material budget as well as new cooling and powering schemes. A new front-end readout chip mitigates buffering and bandwidth limitations, and allows operation at low comparator thresholds. Here in this paper, comprehensive test beam studies are presented, which have been conducted to verify the design and to quantify the performance of the new detector assemblies in terms of tracking efficiency and spatial resolution. Under optimal conditions, the tracking efficiency ismore » $$99.95\\pm0.05\\,\\%$$, while the intrinsic spatial resolutions are $$4.80\\pm0.25\\,\\mu \\mathrm{m}$$ and $$7.99\\pm0.21\\,\\mu \\mathrm{m}$$ along the $$100\\,\\mu \\mathrm{m}$$ and $$150\\,\\mu \\mathrm{m}$$ pixel pitch, respectively. The findings are compared to a detailed Monte Carlo simulation of the pixel detector and good agreement is found.« less

Guide to using Cuechart, Tellagraf, and Disspla at ANL

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

Bertoncini, P.J.; Thommes, M.M.

1986-01-01

Guide to Curchart, Tellagraf, and Disspla at ANL provides information necessary for using the three ISSCO graphics packages at Argonne: Cuechart is a cue-and-response program available in CMS that aids users in creating bar charts, line charts, pie charts, and word charts. It is appropriate for users with little or no previous graphics experience. Cuechart provides much of the capability of Tellagraf without the user's having to learn Tellagraf commands. Tellagraf is a more powerful, easy-to-use graphics package also available in CMS. With a little training, scientists, administrators, and secretaries can produce sophisticated publication-quality log or linear plots, bar charts,more » pie charts, tables, or posters. Disspla is a more versatile and sophisticated graphics package. It is available in both CMS and batch and consists of several hundred Fortran-callable and PL/I-callable subroutines that will enable you to obtain professional quality plots. In addition to log or linear plots, bar charts, pie charts, and pages of text, Disspla provides subroutines for contour plots, 3-D plots, and world maps.« less

Flexible trigger menu implementation on the Global Trigger for the CMS Level-1 trigger upgrade

NASA Astrophysics Data System (ADS)

MATSUSHITA, Takashi; CMS Collaboration

2017-10-01

The CMS experiment at the Large Hadron Collider (LHC) has continued to explore physics at the high-energy frontier in 2016. The integrated luminosity delivered by the LHC in 2016 was 41 fb-1 with a peak luminosity of 1.5 × 1034 cm-2s-1 and peak mean pile-up of about 50, all exceeding the initial estimations for 2016. The CMS experiment has upgraded its hardware-based Level-1 trigger system to maintain its performance for new physics searches and precision measurements at high luminosities. The Global Trigger is the final step of the CMS Level-1 trigger and implements a trigger menu, a set of selection requirements applied to the final list of objects from calorimeter and muon triggers, for reducing the 40 MHz collision rate to 100 kHz. The Global Trigger has been upgraded with state-of-the-art FPGA processors on Advanced Mezzanine Cards with optical links running at 10 GHz in a MicroTCA crate. The powerful processing resources of the upgraded system enable implementation of more algorithms at a time than previously possible, allowing CMS to be more flexible in how it handles the available trigger bandwidth. Algorithms for a trigger menu, including topological requirements on multi-objects, can be realised in the Global Trigger using the newly developed trigger menu specification grammar. Analysis-like trigger algorithms can be represented in an intuitive manner and the algorithms are translated to corresponding VHDL code blocks to build a firmware. The grammar can be extended in future as the needs arise. The experience of implementing trigger menus on the upgraded Global Trigger system will be presented.

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

Muons in the CMS High Level Trigger System

NASA Astrophysics Data System (ADS)

Verwilligen, Piet; CMS Collaboration

2016-04-01

The trigger systems of LHC detectors play a fundamental role in defining the physics capabilities of the experiments. A reduction of several orders of magnitude in the rate of collected events, with respect to the proton-proton bunch crossing rate generated by the LHC, is mandatory to cope with the limits imposed by the readout and storage system. An accurate and efficient online selection mechanism is thus required to fulfill the task keeping maximal the acceptance to physics signals. The CMS experiment operates using a two-level trigger system. Firstly a Level-1 Trigger (L1T) system, implemented using custom-designed electronics, is designed to reduce the event rate to a limit compatible to the CMS Data Acquisition (DAQ) capabilities. A High Level Trigger System (HLT) follows, aimed at further reducing the rate of collected events finally stored for analysis purposes. The latter consists of a streamlined version of the CMS offline reconstruction software and operates on a computer farm. It runs algorithms optimized to make a trade-off between computational complexity, rate reduction and high selection efficiency. With the computing power available in 2012 the maximum reconstruction time at HLT was about 200 ms per event, at the nominal L1T rate of 100 kHz. An efficient selection of muons at HLT, as well as an accurate measurement of their properties, such as transverse momentum and isolation, is fundamental for the CMS physics programme. The performance of the muon HLT for single and double muon triggers achieved in Run I will be presented. Results from new developments, aimed at improving the performance of the algorithms for the harsher scenarios of collisions per event (pile-up) and luminosity expected for Run II will also be discussed.

A transient response analysis of the space shuttle vehicle during liftoff

NASA Technical Reports Server (NTRS)

Brunty, J. A.

1990-01-01

A proposed transient response method is formulated for the liftoff analysis of the space shuttle vehicles. It uses a power series approximation with unknown coefficients for the interface forces between the space shuttle and mobile launch platform. This allows the equation of motion of the two structures to be solved separately with the unknown coefficients at the end of each step. These coefficients are obtained by enforcing the interface compatibility conditions between the two structures. Once the unknown coefficients are determined, the total response is computed for that time step. The method is validated by a numerical example of a cantilevered beam and by the liftoff analysis of the space shuttle vehicles. The proposed method is compared to an iterative transient response analysis method used by Martin Marietta for their space shuttle liftoff analysis. It is shown that the proposed method uses less computer time than the iterative method and does not require as small a time step for integration. The space shuttle vehicle model is reduced using two different types of component mode synthesis (CMS) methods, the Lanczos method and the Craig and Bampton CMS method. By varying the cutoff frequency in the Craig and Bampton method it was shown that the space shuttle interface loads can be computed with reasonable accuracy. Both the Lanczos CMS method and Craig and Bampton CMS method give similar results. A substantial amount of computer time is saved using the Lanczos CMS method over that of the Craig and Bampton method. However, when trying to compute a large number of Lanczos vectors, input/output computer time increased and increased the overall computer time. The application of several liftoff release mechanisms that can be adapted to the proposed method are discussed.

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/.

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

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...

Understanding Collaborative Learning Behavior from Moodle Log Data

ERIC Educational Resources Information Center

Lu, Jingyan; Law, Nancy Wai Ying

2012-01-01

Although course management systems (CMSs) were originally designed for teachers to manage their teaching, little interest has been directed at students' learning. Moodle is usually regarded as a CMS. However, how to make full use of its powerful features and design them into learning tools has rarely been investigated. This study investigates two…

Low latitude middle atmosphere ionization studies

NASA Technical Reports Server (NTRS)

Bassi, J. P.

1976-01-01

Low latitude middle atmosphere ionization was studied with data obtained from three blunt conductivity probes and one Gerdien condenser. An investigation was conducted into the effects of various ionization sources in the 40 to 65 Km altitude range. An observed enhancement of positive ion conductivity taking place during the night can be explained by an atmsopheric effect, with cosmic rays being the only source of ionization only if the ion-ion recombination coefficient (alpha sub i) is small(10 to the -7 power cu cm/s) and varies greatly with altitude. More generally accepted values of alpha sub i ( approximately equal to 3x10 to the -7 power cu cm/s) require an additional source of ionization peaking at about 65 Km, and corresponding approximately to the integrated effect of an X-ray flux measured on a rocket flown in conjunction with the ionization measurements. The reasonable assumption of an alpha sub i which does not vary with altitude in the 50-70 Km range implies an even greater value alpha sub i and a more intense and harder X-ray spectrum.

Education review: applied medical informatics--informatics in medical education.

PubMed

Naeymi-Rad, F; Trace, D; Moidu, K; Carmony, L; Booden, T

1994-05-01

The importance of informatics training within a health sciences program is well recognized and is being implemented on an increasing scale. At Chicago Medical School (CMS), the Informatics program incorporates information technology at every stage of medical education. First-year students are offered an elective in computer topics that concentrate on basic computer literacy. Second-year students learn information management such as entry and information retrieval skills. For example, during the Introduction to Clinical Medicine course, the student is exposed to the Intelligent Medical Record-Entry (IMR-E), allowing the student to enter and organize information gathered from patient encounters. In the third year, students in the Internal Medicine rotation at Norwalk Hospital use Macintosh power books to enter and manage their patients. Patient data gathered by the student are stored in a local server in Norwalk Hospital. In the final year, we teach students the role of informatics in clinical decision making. The present senior class at CMS has been exposed to the power of medical informatics tools for several years. The use of these informatics tools at the point of care is stressed.

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.

Tracking at High Level Trigger in CMS

NASA Astrophysics Data System (ADS)

Tosi, M.

2016-04-01

The trigger systems of the LHC detectors play a crucial role in determining the physics capabilities of experiments. A reduction of several orders of magnitude of the event rate is needed to reach values compatible with detector readout, offline storage and analysis capability. The CMS experiment has been designed with a two-level trigger system: the Level-1 Trigger (L1T), implemented on custom-designed electronics, and the High Level Trigger (HLT), a streamlined version of the CMS offline reconstruction software running on a computer farm. A software trigger system requires a trade-off between the complexity of the algorithms, the sustainable output rate, and the selection efficiency. With the computing power available during the 2012 data taking the maximum reconstruction time at HLT was about 200 ms per event, at the nominal L1T rate of 100 kHz. Track reconstruction algorithms are widely used in the HLT, for the reconstruction of the physics objects as well as in the identification of b-jets and lepton isolation. Reconstructed tracks are also used to distinguish the primary vertex, which identifies the hard interaction process, from the pileup ones. This task is particularly important in the LHC environment given the large number of interactions per bunch crossing: on average 25 in 2012, and expected to be around 40 in Run II. We will present the performance of HLT tracking algorithms, discussing its impact on CMS physics program, as well as new developments done towards the next data taking in 2015.

The GMOD Drupal bioinformatic server framework.

PubMed

Papanicolaou, Alexie; Heckel, David G

2010-12-15

Next-generation sequencing technologies have led to the widespread use of -omic applications. As a result, there is now a pronounced bioinformatic bottleneck. The general model organism database (GMOD) tool kit (http://gmod.org) has produced a number of resources aimed at addressing this issue. It lacks, however, a robust online solution that can deploy heterogeneous data and software within a Web content management system (CMS). We present a bioinformatic framework for the Drupal CMS. It consists of three modules. First, GMOD-DBSF is an application programming interface module for the Drupal CMS that simplifies the programming of bioinformatic Drupal modules. Second, the Drupal Bioinformatic Software Bench (biosoftware_bench) allows for a rapid and secure deployment of bioinformatic software. An innovative graphical user interface (GUI) guides both use and administration of the software, including the secure provision of pre-publication datasets. Third, we present genes4all_experiment, which exemplifies how our work supports the wider research community. Given the infrastructure presented here, the Drupal CMS may become a powerful new tool set for bioinformaticians. The GMOD-DBSF base module is an expandable community resource that decreases development time of Drupal modules for bioinformatics. The biosoftware_bench module can already enhance biologists' ability to mine their own data. The genes4all_experiment module has already been responsible for archiving of more than 150 studies of RNAi from Lepidoptera, which were previously unpublished. Implemented in PHP and Perl. Freely available under the GNU Public License 2 or later from http://gmod-dbsf.googlecode.com.

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.

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.

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.

The effect of chinese herbal medicine Banxia Baizhu Tianma Decoction for the treatment of vertebrobasilar insufficiency vertigo: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Guo, ZhenLang; Su, ZhenNing; Wang, ZhengFei; Luo, XiaoMu; Lai, RenKui

2017-04-01

Banxia Baizhu Tianma Decoction (BBTD) is widely used to treat vertebrobasilar insufficiency vertigo (VBIV) in China, but its efficacy remains largely unexplored. We systemically summarized relevant evidence from randomized controlled trials (RCTs) to assess the therapeutic effect of BBTD. Seven electronic databases were searched for relevant electronic studies published before July 2016. We evaluated RCTs that compared BBTD, anti-vertigo drugs and a combination of BBTD and anti-vertigo drugs. We performed a meta-analysis in accordance with the Cochrane Collaboration criteria. The outcomes were clinical efficacy (CE), blood flow velocity of the vertebrobasilar artery by transcranial Doppler (TCD), and adverse effects. Twenty-seven studies with a total of 2796 patients were identified. Compared with anti-vertigo drugs, BBTD showed slight effects on CE (n=350; RR, 1.09; 95% CI, 1.01-1.18; p=0.03; I 2 =0%); however, BBTD plus anti-vertigo drugs (BPAD) significantly improved the clinical efficacy (n=2446; RR, 1.20; 95% CI, 1.16-1.24; p<0.00001; I 2 =0%) and accelerated the blood flow velocity of the left vertebral artery (LVA) (n=1444; WMD, 5.21cm/s; 95% CI, 3.72-6.70cm/s; p<0.00001; I 2 =91%), the blood flow velocity of the right vertebral artery (RVA) (n=1444; WMD, 5.45cm/s; 95% CI, 4.02-6.88cm/s; p<0.00001; I 2 =89%), and the blood flow velocity of the basilar artery (BA) (n=1872; WMD, 5.20cm/s; 95% CI, 3.86-6.54cm/s; p<0.00001; I 2 =90%). Adverse effects were mentioned in six studies. The current evidence indicates that BPAD is effective for the treatment of VBIV, but the efficacy and safety of BBTD is uncertain because of the limited number of trials and low methodological quality. Hence, high-quality and adequately powered RCTs are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

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...

Electronics and triggering challenges for the CMS High Granularity Calorimeter

NASA Astrophysics Data System (ADS)

Lobanov, A.

2018-02-01

The High Granularity Calorimeter (HGCAL), presently being designed by the CMS collaboration to replace the CMS endcap calorimeters for the High Luminosity phase of LHC, will feature six million channels distributed over 52 longitudinal layers. The requirements for the front-end electronics are extremely challenging, including high dynamic range (0.2 fC-10 pC), low noise (~2000 e- to be able to calibrate on single minimum ionising particles throughout the detector lifetime) and low power consumption (~20 mW/channel), as well as the need to select and transmit trigger information with a high granularity. Exploiting the intrinsic precision-timing capabilities of silicon sensors also requires careful design of the front-end electronics as well as the whole system, particularly clock distribution. The harsh radiation environment and requirement to keep the whole detector as dense as possible will require novel solutions to the on-detector electronics layout. Processing the data from the HGCAL imposes equally large challenges on the off-detector electronics, both for the hardware and incorporated algorithms. We present an overview of the complete electronics architecture, as well as the performance of prototype components and algorithms.

A Study of the Effects of Sensor Noise and Guidance Laws on SAM Effectiveness Against Cruise Missiles

DTIC Science & Technology

2015-06-01

submarines, or from the ground. Most CMs use air- breathing engines (i.e., pulsejet, ramjet, turbojet, or turbofan ), and some use rocket motors...lateral acceleration for a Turbofan engine–powered Tomahawk [26]. 1. Target Motion Using the same concept as in missile motion, we get the target

Technical Note: A new phantom design for routine testing of Doppler ultrasound.

PubMed

Grice, J V; Pickens, D R; Price, R R

2016-07-01

The objective of this project is to demonstrate the principle and operation for a simple, inexpensive, and highly portable Doppler ultrasound quality assurance (QA) phantom intended for routine QA testing. A prototype phantom has been designed, fabricated, and evaluated. The phantom described here is powered by gravity alone, requires no external equipment for operation, and produces a stable fluid velocity useful for quality assurance. Many commercially available Doppler ultrasound testing systems can suffer from issues such as a lengthy setup, prohibitive cost, nonportable size, or difficulty in use. This new phantom design aims to address some of these problems and create a phantom appropriate for assessing Doppler ultrasound stability. The phantom was fabricated using a 3D printer. The basic design of the phantom is to provide gravity-powered flow of a Doppler fluid between two reservoirs. The printed components were connected with latex tubing and then seated in a tissue mimicking gel. Spectral Doppler waveforms were sampled to evaluate variations in the data, and the phantom was evaluated using high frame rate video to find an alternate measure of mean fluid velocity flowing in the phantom. The current system design maintains stable flow from one reservoir to the other for approximately 7 s. Color Doppler imaging of the phantom was found to be qualitatively consistent with laminar flow. Using pulsed spectral Doppler, the average fluid velocity from a sample volume approximately centered in the synthetic vessel was measured to be 56 cm/s with a standard deviation of 3.2 cm/s across 118 measurements. An independent measure of the average fluid velocity was measured to be 51.9 cm/s with a standard deviation of 0.7 cm/s over 4 measurements. The developed phantom provides stable fluid flow useful for frequent clinical Doppler ultrasound testing and attempts to address several obstacles facing Doppler phantom testing. Such an ultrasound phantom can make routine testing more approachable for institutions that wish to initiate a Doppler QA program or complement a previously existing QA program.

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...

Legacy2Drupal - Conversion of an existing oceanographic relational database to a semantically enabled Drupal content management system

NASA Astrophysics Data System (ADS)

Maffei, A. R.; Chandler, C. L.; Work, T.; Allen, J.; Groman, R. C.; Fox, P. A.

2009-12-01

Content Management Systems (CMSs) provide powerful features that can be of use to oceanographic (and other geo-science) data managers. However, in many instances, geo-science data management offices have previously designed customized schemas for their metadata. The WHOI Ocean Informatics initiative and the NSF funded Biological Chemical and Biological Data Management Office (BCO-DMO) have jointly sponsored a project to port an existing, relational database containing oceanographic metadata, along with an existing interface coded in Cold Fusion middleware, to a Drupal6 Content Management System. The goal was to translate all the existing database tables, input forms, website reports, and other features present in the existing system to employ Drupal CMS features. The replacement features include Drupal content types, CCK node-reference fields, themes, RDB, SPARQL, workflow, and a number of other supporting modules. Strategic use of some Drupal6 CMS features enables three separate but complementary interfaces that provide access to oceanographic research metadata via the MySQL database: 1) a Drupal6-powered front-end; 2) a standard SQL port (used to provide a Mapserver interface to the metadata and data; and 3) a SPARQL port (feeding a new faceted search capability being developed). Future plans include the creation of science ontologies, by scientist/technologist teams, that will drive semantically-enabled faceted search capabilities planned for the site. Incorporation of semantic technologies included in the future Drupal 7 core release is also anticipated. Using a public domain CMS as opposed to proprietary middleware, and taking advantage of the many features of Drupal 6 that are designed to support semantically-enabled interfaces will help prepare the BCO-DMO database for interoperability with other ecosystem databases.

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.

The GMOD Drupal Bioinformatic Server Framework

PubMed Central

Papanicolaou, Alexie; Heckel, David G.

2010-01-01

Motivation: Next-generation sequencing technologies have led to the widespread use of -omic applications. As a result, there is now a pronounced bioinformatic bottleneck. The general model organism database (GMOD) tool kit (http://gmod.org) has produced a number of resources aimed at addressing this issue. It lacks, however, a robust online solution that can deploy heterogeneous data and software within a Web content management system (CMS). Results: We present a bioinformatic framework for the Drupal CMS. It consists of three modules. First, GMOD-DBSF is an application programming interface module for the Drupal CMS that simplifies the programming of bioinformatic Drupal modules. Second, the Drupal Bioinformatic Software Bench (biosoftware_bench) allows for a rapid and secure deployment of bioinformatic software. An innovative graphical user interface (GUI) guides both use and administration of the software, including the secure provision of pre-publication datasets. Third, we present genes4all_experiment, which exemplifies how our work supports the wider research community. Conclusion: Given the infrastructure presented here, the Drupal CMS may become a powerful new tool set for bioinformaticians. The GMOD-DBSF base module is an expandable community resource that decreases development time of Drupal modules for bioinformatics. The biosoftware_bench module can already enhance biologists' ability to mine their own data. The genes4all_experiment module has already been responsible for archiving of more than 150 studies of RNAi from Lepidoptera, which were previously unpublished. Availability and implementation: Implemented in PHP and Perl. Freely available under the GNU Public License 2 or later from http://gmod-dbsf.googlecode.com Contact: alexie@butterflybase.org PMID:20971988

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

Periodic gamma-ray emissions from Geminga at or = 10(12) eV

NASA Technical Reports Server (NTRS)

Kaul, R. K.; Rawat, H. S.; Sanecha, V. K.; Rannot, R. C.; Sapru, M.; Tickoo, A. K.; Qazi, R. A.; Bhat, C. L.; Razdan, H.; Tonwar, S. C.

1985-01-01

Analysis of data from an atmospheric Cerenkov telescope indicated the periodic emission of gamma rays of energy 10 to the 12th power eV, at 60.25 second period, from 2CG 195+4. The gamma ray flux at 99% confidence level is estimated to be 9.5 x 10 to 12 photons/sq cm/s.

Energy and momentum relaxation of electrons in bulk and 2D GaN

NASA Astrophysics Data System (ADS)

Zanato, D.; Balkan, N.; Hill, G.; Schaff, W. J.

2004-10-01

We present our experimental and theoretical studies regarding the energy and momentum relaxation of hot electrons in n-type bulk GaN and AlGaN/GaN HEMT structures. We determine the non-equilibrium temperatures and the energy relaxation rates in the steady state using the mobility mapping technique together with the power balance conditions as described by us elsewhere [N. Balkan, M.C. Arikan, S. Gokden, V. Tilak, B. Schaff, R.J. Shealy, J. Phys.: Condens. Matter 14 (2002) 3457]. We obtain the e-LO phonon scattering time of 8 fs and show that the power loss of electrons due to optical phonon emission agrees with the theoretical prediction. The drift velocity-field curves at high electric fields indicate that the drift velocity saturates at approximately 3×10 6 cm/s for the two-dimensional structure and 4×10 6 cm/s for the bulk material at 77 K. These values are much lower than those predicted by the existing theories. A critical analysis of the observations is given with a model taking into account of the non-drifting non-equilibrium phonon production.

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.

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.

Мюонный комплекс и преконвертор электромагнитного калориметра установки CDF II в экспериментах по физике тяжелых кварков на Тэватроне (in Russian)

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

Artikov, Akram Muzafarovich

The object of this investigation is to understand processes with c,b,t-quarks, muon system and trigger preshower of the electromagnetic calorimeter, plastic scintillation detectors of the CDFII setup.

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.

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.

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.

Stocks, Flows, and Distribution of Critical Metals in Embedded Electronics in Passenger Vehicles.

PubMed

Restrepo, Eliette; Løvik, Amund N; Wäger, Patrick; Widmer, Rolf; Lonka, Radek; Müller, Daniel B

2017-02-07

One of the major applications of critical metals (CMs) is in electrical and electronic equipment (EEE), which is increasingly embedded in other products, notably passenger vehicles. However, recycling strategies for future CM quantities in end-of-life vehicles (ELVs) are poorly understood, mainly due to a limited understating of the complexity of automotive embedded EEE. We introduce a harmonization of the network structure of automotive electronics that enables a comprehensive quantification of CMs in all embedded EEE in a vehicle. This network is combined with a material flow analysis along the vehicle lifecycle in Switzerland to quantify the stocks and flows of Ag, Au, Pd, Ru, Dy, La, Nd, and Co in automotive embedded EEE. In vehicles in use, we calculated 5 -2 +3 t precious metals in controllers embedded in all vehicle types and 220 -60 +90 t rare earth elements (REE); found mainly in five electric motors: alternator, starter, radiator-fan and electronic power steering motor embedded in conventional passenger vehicles and drive motor/generator embedded in hybrid and electric vehicles. Dismantling these devices before ELV shredding, as well as postshredder treatment of automobile shredder residue may increase the recovery of CMs from ELVs. Environmental and economic implications of such recycling strategies must be considered.

tkLayout: a design tool for innovative silicon tracking detectors

NASA Astrophysics Data System (ADS)

Bianchi, G.

2014-03-01

A new CMS tracker is scheduled to become operational for the LHC Phase 2 upgrade in the early 2020's. tkLayout is a software package developed to create 3d models for the design of the CMS tracker and to evaluate its fundamental performance figures. The new tracker will have to cope with much higher luminosity conditions, resulting in increased track density, harsher radiation exposure and, especially, much higher data acquisition bandwidth, such that equipping the tracker with triggering capabilities is envisaged. The design of an innovative detector involves deciding on an architecture offering the best trade-off among many figures of merit, such as tracking resolution, power dissipation, bandwidth, cost and so on. Quantitatively evaluating these figures of merit as early as possible in the design phase is of capital importance and it is best done with the aid of software models. tkLayout is a flexible modeling tool: new performance estimates and support for different detector geometries can be quickly added, thanks to its modular structure. Besides, the software executes very quickly (about two minutes), so that many possible architectural variations can be rapidly modeled and compared, to help in the choice of a viable detector layout and then to optimize it. A tracker geometry is generated from simple configuration files, defining the module types, layout and materials. Support structures are automatically added and services routed to provide a realistic tracker description. The tracker geometries thus generated can be exported to the standard CMS simulation framework (CMSSW) for full Monte Carlo studies. tkLayout has proven essential in giving guidance to CMS in studying different detector layouts and exploring the feasibility of innovative solutions for tracking detectors, in terms of design, performance and projected costs. This tool has been one of the keys to making important design decisions for over five years now and has also enabled project engineers and simulation experts to focus their efforts on other important or specific issues. Even if tkLayout was designed for the CMS tracker upgrade project, its flexibility makes it experiment-agnostic, so that it could be easily adapted to model other tracking detectors. The technology behind tkLayout is presented, as well as some of the results obtained in the context of the CMS silicon tracker design studies.

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.

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...

Comment on measuring the tt forward-backward asymmetry at ATLAS and CMS

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

Arguin, Jean-Francois; Ligeti, Zoltan; Freytsis, Marat

2011-10-01

We suggest a new possibility for ATLAS and CMS to explore the tt forward-backward asymmetry measured at the Tevatron, by attempting to reconstruct tt events, with one of the tops decaying semileptonically in the central region (|{eta}|<2.5) and the other decaying hadronically in the forward region (|{eta}|>2.5). For several models which give comparable Tevatron signals, we study the charge asymmetry at the LHC as a function of cuts on |{eta}| and on the tt invariant mass, m{sub tt}. We show that there is an interesting complementarity between cuts on |{eta}| and m{sub tt} to suppress the dominant and symmetric gg{yields}ttmore » rate, and different combinations of cuts enhance the distinguishing power between models. This complementarity is likely to hold in other new physics scenarios as well, which affect the tt cross section, so it motivates extending tt reconstruction to higher |{eta}|.« less

MUSiC - Model-independent search for deviations from Standard Model predictions in CMS

NASA Astrophysics Data System (ADS)

Pieta, Holger

2010-02-01

We present an approach for a model independent search in CMS. Systematically scanning the data for deviations from the standard model Monte Carlo expectations, such an analysis can help to understand the detector and tune event generators. By minimizing the theoretical bias the analysis is furthermore sensitive to a wide range of models for new physics, including the uncounted number of models not-yet-thought-of. After sorting the events into classes defined by their particle content (leptons, photons, jets and missing transverse energy), a minimally prejudiced scan is performed on a number of distributions. Advanced statistical methods are used to determine the significance of the deviating regions, rigorously taking systematic uncertainties into account. A number of benchmark scenarios, including common models of new physics and possible detector effects, have been used to gauge the power of such a method. )

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

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

Solid State Research.

DTIC Science & Technology

1996-05-15

Turner Y.-H. Zhang* 1996 Pittsburgh Conference, Chicago, Illinois, 3-8 March 1996 The Linearized Series Mach-Zehnder Interferometric Modulator for...examined using Nomarski contrast microscopy, is mirror and featureless, unlike AlGaSb layers that have exhibited a Crosshatch pattern [7]. Double...the surface under Nomarski optical imagery. Figure 3-2 shows linewidth data as the laser power is varied using a 4-^um laser spot size and 5-cm/s

Measurement of the iron spectrum from 60 to 200 GeV per nucleon

NASA Technical Reports Server (NTRS)

Streitmatter, R. E.; Balasubrahmanyan, V. K.; Ormes, J. F.; Acharya, B. S.

1985-01-01

The high energy gas Cerenkov Spectrometer (HEGCS) was flown by balloon from Palestine, Texas on September 30, 1983. The instrument maintained an altitude of 118,000 ft (4.7 g/sq cms) for 6 hours. Details of the ongoing data analysis and preliminary results on the Fe spectrum to 10 to the 13th power eV/nucleus are given.

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

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.

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).

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

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.

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...

Legacy2Drupal: Conversion of an existing relational oceanographic database to a Drupal 7 CMS

NASA Astrophysics Data System (ADS)

Work, T. T.; Maffei, A. R.; Chandler, C. L.; Groman, R. C.

2011-12-01

Content Management Systems (CMSs) such as Drupal provide powerful features that can be of use to oceanographic (and other geo-science) data managers. However, in many instances, geo-science data management offices have already designed and implemented customized schemas for their metadata. The NSF funded Biological Chemical and Biological Data Management Office (BCO-DMO) has ported an existing relational database containing oceanographic metadata, along with an existing interface coded in Cold Fusion middleware, to a Drupal 7 Content Management System. This is an update on an effort described as a proof-of-concept in poster IN21B-1051, presented at AGU2009. The BCO-DMO project has translated all the existing database tables, input forms, website reports, and other features present in the existing system into Drupal CMS features. The replacement features are made possible by the use of Drupal content types, CCK node-reference fields, a custom theme, and a number of other supporting modules. This presentation describes the process used to migrate content in the original BCO-DMO metadata database to Drupal 7, some problems encountered during migration, and the modules used to migrate the content successfully. Strategic use of Drupal 7 CMS features that enable three separate but complementary interfaces to provide access to oceanographic research metadata will also be covered: 1) a Drupal 7-powered user front-end; 2) REST-ful JSON web services (providing a Mapserver interface to the metadata and data; and 3) a SPARQL interface to a semantic representation of the repository metadata (this feeding a new faceted search capability currently under development). The existing BCO-DMO ontology, developed in collaboration with Rensselaer Polytechnic Institute's Tetherless World Constellation, makes strategic use of pre-existing ontologies and will be used to drive semantically-enabled faceted search capabilities planned for the site. At this point, the use of semantic technologies included in the Drupal 7 core is anticipated. Using a public domain CMS as opposed to proprietary middleware, and taking advantage of the many features of Drupal 7 that are designed to support semantically-enabled interfaces will help prepare the BCO-DMO and other science data repositories for interoperability between systems that serve ecosystem research data.

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.

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.

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...

Time-dependent evolution of functional vs. remodeling signaling in induced pluripotent stem cell-derived cardiomyocytes and induced maturation with biomechanical stimulation.

PubMed

Jung, Gwanghyun; Fajardo, Giovanni; Ribeiro, Alexandre J S; Kooiker, Kristina Bezold; Coronado, Michael; Zhao, Mingming; Hu, Dong-Qing; Reddy, Sushma; Kodo, Kazuki; Sriram, Krishna; Insel, Paul A; Wu, Joseph C; Pruitt, Beth L; Bernstein, Daniel

2016-04-01

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful platform for uncovering disease mechanisms and assessing drugs for efficacy/toxicity. However, the accuracy with which hiPSC-CMs recapitulate the contractile and remodeling signaling of adult cardiomyocytes is not fully known. We used β-adrenergic receptor (β-AR) signaling as a prototype to determine the evolution of signaling component expression and function during hiPSC-CM maturation. In "early" hiPSC-CMs (less than or equal to d 30), β2-ARs are a primary source of cAMP/PKA signaling. With longer culture, β1-AR signaling increases: from 0% of cAMP generation at d 30 to 56.8 ± 6.6% by d 60. PKA signaling shows a similar increase: 15.7 ± 5.2% (d 30), 49.8 ± 0.5% (d 60), and 71.0 ± 6.1% (d 90). cAMP generation increases 9-fold from d 30 to 60, with enhanced coupling to remodeling pathways (e.g., Akt and Ca(2+)/calmodulin-dependent protein kinase type II) and development of caveolin-mediated signaling compartmentalization. By contrast, cardiotoxicity induced by chronic β-AR stimulation, a major component of heart failure, develops much later: 5% cell death at d 30vs 55% at d 90. Moreover, β-AR maturation can be accelerated by biomechanical stimulation. The differential maturation of β-AR functionalvs remodeling signaling in hiPSC-CMs has important implications for their use in disease modeling and drug testing. We propose that assessment of signaling be added to the indices of phenotypic maturation of hiPSC-CMs.-Jung, G., Fajardo, G., Ribeiro, A. J. S., Kooiker, K. B., Coronado, M., Zhao, M., Hu, D.-Q., Reddy, S., Kodo, K., Sriram, K., Insel, P. A., Wu, J. C., Pruitt, B. L., Bernstein, D. Time-dependent evolution of functionalvs remodeling signaling in induced pluripotent stem cell-derived cardiomyocytes and induced maturation with biomechanical stimulation. © FASEB.

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.

Detector Powering in the 21st Century Why stay stuck with the Good old 20th Century methods?

NASA Astrophysics Data System (ADS)

Dhawan, Satish; Sumner, Richard

Future Collider Physics Detectors are envisioned with large granularity but we have a power delivery problem unless we fill a large fraction of the detector volume with copper conductors. LHC detector electronics is powered by transporting direct current over distances of 30 to 150 meters. This is how Thomas Alva Edison powered his light bulb. For example, CMS ECAL uses 50 kiloamps at 2.5 volts, supplied over a cable set with a transmission efficiency of only 30%. The transmission loss becomes waste heat in the detector that has to be removed. We have been exploring methods to transmit the DC power at higher voltage (low current), reducing to the final low voltage (high current) using DC-DC converters. These converters must operate in high magnetic fields and high radiation levels. This requires rad hard components and non-magnetic (air core) inductors.

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.

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...

Combustion of Solids in Microgravity: Results from the BASS-II Experiment

NASA Technical Reports Server (NTRS)

Ferkul, Paul V.; Bhattacharjee, Subrata; Fernandez-Pello, Carlos; Miller, Fletcher; Olson, Sandra L.; Takahashi, Fumiaki; T’ien, James S.

2014-01-01

The Burning and Suppression of Solids-II (BASS-II) experiment was performed on the International Space Station. Microgravity combustion tests burned thin and thick flat samples, acrylic slabs, spheres, and cylinders. The samples were mounted inside a small wind tunnel which could impose air flow speeds up to 53 cms. The wind tunnel was installed in the Microgravity Science Glovebox which supplied power, imaging, and a level of containment. The effects of air flow speed, fuel thickness, fuel preheating, and oxygen concentration on flame appearance, growth, spread rate, and extinction were examined in both the opposed and concurrent flow configuration. The flames are quite sensitive to air flow speed in the range 0 to 5 cms. They can be sustained at very low flow speeds of less than 1 cms, when they become dim blue and stable. In this state they are not particularly dangerous from a fire safety perspective, but they can flare up quickly with a sudden increase in air flow speed. Including earlier BASS-I results, well over one hundred tests have been conducted of the various samples in the different geometries, flow speeds, and oxygen concentrations. There are several important implications related to fundamental combustion research as well as spacecraft fire safety. This work was supported by the NASA Space Life and Physical Sciences Research and Applications Division (SLPSRA).

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.

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.

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.

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

Verification and Validation of the Coastal Modeling System. Report 3: CMS-Flow: Hydrodynamics

DTIC Science & Technology

2011-12-01

Jansen (1978) Spectrum TMA Directional spreading distribution Cosine Power Directional spreading parameter γ 3.3 Bottom friction Off (default...Ramp duration 3 hr The wave breaking formula applied was Battjes and Jansen (1978) because it is the recommended wave breaking formula when using...Li, Z.H., K.D. Nguyen , J.C. Brun-Cottan and J.M. Martin. 1994. Numerical simulation of the turbidity maximum transport in the Gironde Estuary (France

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

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.

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

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.

Hair-based sensors for micro-autonomous systems

NASA Astrophysics Data System (ADS)

Sadeghi, Mahdi M.; Peterson, Rebecca L.; Najafi, Khalil

2012-06-01

We seek to harness microelectromechanical systems (MEMS) technologies to build biomimetic devices for low-power, high-performance, robust sensors and actuators on micro-autonomous robot platforms. Hair is used abundantly in nature for a variety of functions including balance and inertial sensing, flow sensing and aerodynamic (air foil) control, tactile and touch sensing, insulation and temperature control, particle filtering, and gas/chemical sensing. Biological hairs, which are typically characterized by large surface/volume ratios and mechanical amplification of movement, can be distributed in large numbers over large areas providing unprecedented sensitivity, redundancy, and stability (robustness). Local neural transduction allows for space- and power-efficient signal processing. Moreover by varying the hair structure and transduction mechanism, the basic hair form can be used for a wide diversity of functions. In this paper, by exploiting a novel wafer-level, bubble-free liquid encapsulation technology, we make arrays of micro-hydraulic cells capable of electrostatic actuation and hydraulic amplification, which enables high force/high deflection actuation and extremely sensitive detection (sensing) at low power. By attachment of cilia (hair) to the micro-hydraulic cell, air flow sensors with excellent sensitivity (< few cm/s) and dynamic range (> 10 m/s) have been built. A second-generation design has significantly reduced the sensor response time while maintaining sensitivity of about 2 cm/s and dynamic range of more than 15 m/s. These sensors can be used for dynamic flight control of flying robots or for situational awareness in surveillance applications. The core biomimetic technologies developed are applicable to a broad range of sensors and actuators.

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...

Measurement of the Width and Skewness of Elliptic Flow Fluctuations in PbPb Collisions at 5.02 TeV with CMS

NASA Astrophysics Data System (ADS)

Castle, James R.; CMS Collaboration

2017-11-01

Flow harmonic fluctuations are studied for PbPb collisions at √{sNN} = 5.02 TeV using the CMS detector at the LHC. Flow harmonic probability distributions p(v2) are obtained by unfolding smearing effects from observed azimuthal anisotropy distributions using particles of 0.3

Optical Comb from a Whispering Gallery Mode Resonator for Spectroscopy and Astronomy Instruments Calibration

NASA Technical Reports Server (NTRS)

Strekalov, Dmitry V.; Yu, Nam; Thompson, Robert J.

2012-01-01

The most accurate astronomical data is available from space-based observations that are not impeded by the Earth's atmosphere. Such measurements may require spectral samples taken as long as decades apart, with the 1 cm/s velocity precision integrated over a broad wavelength range. This raises the requirements specifically for instruments used in astrophysics research missions -- their stringent wavelength resolution and accuracy must be maintained over years and possibly decades. Therefore, a stable and broadband optical calibration technique compatible with spaceflights becomes essential. The space-based spectroscopic instruments need to be calibrated in situ, which puts forth specific requirements to the calibration sources, mainly concerned with their mass, power consumption, and reliability. A high-precision, high-resolution reference wavelength comb source for astronomical and astrophysics spectroscopic observations has been developed that is deployable in space. The optical comb will be used for wavelength calibrations of spectrographs and will enable Doppler measurements to better than 10 cm/s precision, one hundred times better than the current state-of-the- art.

Upper limits to the annihilation radiation luminosity of Centaurus A

NASA Technical Reports Server (NTRS)

Gehrels, N.; Cline, T. L.; Paciesas, W. S.; Teegarden, B. J.; Tueller, J.; Dirouchoux, P.; Hameury, J. M.

1983-01-01

A high resolution observation of the active nucleus galaxy Centaurus A (NGC 5128) was made by the GSFC low energy gamma-ray spectrometer (LEGS) during a balloon flight on 1981 November 19. The measured spectrum between 70 and 500 keV is well represented by a power law of the form 1.05 x 10 (-4) (E/100 keV) (-1.59) ph/sq cm/s with no breaks or line features observed. The 98 percent confidence (2 sigma) flux upper limit for a narrow (3 keV) 511-keV positron annihilation line is 9.9 x 10 (-4) ph/sq cm/s. Using this upper limit, the ratio of the narrow-line annihilation radiation luminosity to the integral or = 511 keV luminosity is estimated to be 0.09 (2 sigma upper limit). This is compared with the measured value for our Galactic center in the Fall of 1979 of 0.10 to 0.13, indicating a difference in the emission regions in the nuclei of the two galaxies.

Production of D0 meson in pp and PbPb Collisions at √SNN = 5.02 TeV with CMS

NASA Astrophysics Data System (ADS)

Lee, Yen-Jie

2018-02-01

Heavy flavour mesons are used as powerful tools for the study of the strongly interacting medium in heavy ion collisions as heavy quarks are sensitive to the transport properties of the medium. In these proceedings, D0 nuclear modification factors, comparing the yields in PbPb and pp collisions, and azimuthal anisotropies in PbPb collisions are reported. Prompt D0 mesons and their antiparticles have been measured with the CMS detector via the hadronic decay channels D0 → K-π+ and D0 → K+π- in PbPb and pp collisions at a centre-of-mass energy of 5.02 TeV. Nonprompt D0 from b quark decays are subtracted. The D0 results are compared to inclusive charged particles, non-prompt J/ψ mesons from b decays and B+ mesons in order to reveal possible meson mass dependence of the observables.

Crisis Management Systems: A Case Study for Aspect-Oriented Modeling

NASA Astrophysics Data System (ADS)

Kienzle, Jörg; Guelfi, Nicolas; Mustafiz, Sadaf

The intent of this document is to define a common case study for the aspect-oriented modeling research community. The domain of the case study is crisis management systems, i.e., systems that help in identifying, assessing, and handling a crisis situation by orchestrating the communication between all parties involved in handling the crisis, by allocating and managing resources, and by providing access to relevant crisis-related information to authorized users. This document contains informal requirements of crisis management systems (CMSs) in general, a feature model for a CMS product line, use case models for a car crash CMS (CCCMS), a domain model for the CCCMS, an informal physical architecture description of the CCCMS, as well as some design models of a possible object-oriented implementation of parts of the CCCMS backend. AOM researchers who want to demonstrate the power of their AOM approach or technique can hence apply the approach at the most appropriate level of abstraction.

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.

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.

A novel totivirus and piscine reovirus (PRV) in Atlantic salmon (Salmo salar) with cardiomyopathy syndrome (CMS).

PubMed

Løvoll, Marie; Wiik-Nielsen, Jannicke; Grove, Søren; Wiik-Nielsen, Christer R; Kristoffersen, Anja B; Faller, Randi; Poppe, Trygve; Jung, Joonil; Pedamallu, Chandra S; Nederbragt, Alexander J; Meyerson, Matthew; Rimstad, Espen; Tengs, Torstein

2010-11-10

Cardiomyopathy syndrome (CMS) is a severe disease affecting large farmed Atlantic salmon. Mortality often appears without prior clinical signs, typically shortly prior to slaughter. We recently reported the finding and the complete genomic sequence of a novel piscine reovirus (PRV), which is associated with another cardiac disease in Atlantic salmon; heart and skeletal muscle inflammation (HSMI). In the present work we have studied whether PRV or other infectious agents may be involved in the etiology of CMS. Using high throughput sequencing on heart samples from natural outbreaks of CMS and from fish experimentally challenged with material from fish diagnosed with CMS a high number of sequence reads identical to the PRV genome were identified. In addition, a sequence contig from a novel totivirus could also be constructed. Using RT-qPCR, levels of PRV in tissue samples were quantified and the totivirus was detected in all samples tested from CMS fish but not in controls. In situ hybridization supported this pattern indicating a possible association between CMS and the novel piscine totivirus. Although causality for CMS in Atlantic salmon could not be proven for either of the two viruses, our results are compatible with a hypothesis where, in the experimental challenge studied, PRV behaves as an opportunist whereas the totivirus might be more directly linked with the development of CMS.

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.

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

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.

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

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...

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

Thickness and Fuel Preheating Effects on Material Flammability in Microgravity from the BASS Experiment

NASA Technical Reports Server (NTRS)

Ferkul, Paul V.; Olson, Sandra L.; Takahashi, Fumiaki; Endo, Makoto; Johnson, Michael C.; T'ien, James S.

2013-01-01

The Burning and Suppression of Solids (BASS) experiment was performed on the International Space Station. Microgravity combustion tests burning thin and thick flat samples, acrylic spheres, and candles were conducted. The samples were mounted inside a small wind tunnel which could impose air flow speeds up to 40 cms. The wind tunnel was installed in the Microgravity Science Glovebox which supplied power, imaging, and a level of containment. The effects of air flow speed, fuel thickness, fuel preheating, and nitrogen dilution on flame appearance, flame growth, and spread rates were determined in both the opposed and concurrent flow configuration. In some cases, a jet of nitrogen was introduced to attempt to extinguish the flame. Microgravity flames were found to be especially sensitive to air flow speed in the range 0 to 5 cms. The gas phase response is much faster compared to the solid and so as the flow speed is changed, the flame responds with almost no delay. At the lowest speeds examined (less than 1 cms) all the flames tended to become dim blue and very stable. However, heat loss at these very low convective rates is small so the flames can burn for a long time. At moderate flow speeds (between about 1 and 5 cms) the flame continually heats the solid fuel resulting in an increasing fuel temperature, higher rate of fuel vaporization, and a stronger, more luminous flame as time progresses. Only the smallest flames burning acrylic slabs appeared to be adversely influenced by solid conductive heat loss, but even these burned for over 5 minutes before self-extinguishing. This has implications for spacecraft fire safety since a tiny flame might be undetected for a long time. While the small flame is not particularly hazardous if it remains small, the danger is that it might flare up if the air convection is suddenly increased or if the flame spreads into another fuel source.

Comparative analysis of the effects of electron and hole capture on the power characteristics of a semiconductor quantum-well laser

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

Sokolova, Z. N., E-mail: Zina.Sokolova@mail.ioffe.ru; Pikhtin, N. A.; Tarasov, I. S.

The operating characteristics of a semiconductor quantum-well laser calculated using three models are compared. These models are (i) a model not taking into account differences between the electron and hole parameters and using the electron parameters for both types of charge carriers; (ii) a model, which does not take into account differences between the electron and hole parameters and uses the hole parameters for both types of charge carriers; and (iii) a model taking into account the asymmetry between the electron and hole parameters. It is shown that, at the same velocity of electron and hole capture into an unoccupiedmore » quantum well, the laser characteristics, obtained using the three models, differ considerably. These differences are due to a difference between the filling of the electron and hole subbands in a quantum well. The electron subband is more occupied than the hole subband. As a result, at the same velocities of electron and hole capture into an empty quantum well, the effective electron-capture velocity is lower than the effective hole-capture velocity. Specifically, it is shown that for the laser structure studied the hole-capture velocity of 5 × 10{sup 5} cm/s into an empty quantum well and the corresponding electron-capture velocity of 3 × 10{sup 6} cm/s into an empty quantum well describe the rapid capture of these carriers, at which the light–current characteristic of the laser remains virtually linear up to high pump-current densities. However, an electron-capture velocity of 5 × 10{sup 5} cm/s and a corresponding hole-capture velocity of 8.4 × 10{sup 4} cm/s describe the slow capture of these carriers, causing significant sublinearity in the light–current characteristic.« less

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.

Electrical guidance efficiency of downstream-migrating juvenile Sea Lamprey decreases with increasing water velocity

USGS Publications Warehouse

Miehls, Scott M.; Johnson, Nicholas; Haro, Alexander

2017-01-01

We tested the efficacy of a vertically oriented field of pulsed direct current (VEPDC) created by an array of vertical electrodes for guiding downstream-moving juvenile Sea Lampreys Petromyzon marinus to a bypass channel in an artificial flume at water velocities of 10–50 cm/s. Sea Lampreys were more likely to be captured in the bypass channel than in other sections of the flume regardless of electric field status (on or off) or water velocity. Additionally, Sea Lampreys were more likely to be captured in the bypass channel when the VEPDC was active; however, an interaction between the effects of VEPDC and water velocity was observed, as the likelihood of capture decreased with increases in water velocity. The distribution of Sea Lampreys shifted from right to left across the width of the flume toward the bypass channel when the VEPDC was active at water velocities less than 25 cm/s. The VEPDC appeared to have no effect on Sea Lamprey distribution in the flume at water velocities greater than 25 cm/s. We also conducted separate tests to determine the threshold at which Sea Lampreys would become paralyzed. Individuals were paralyzed at a mean power density of 37.0 µW/cm3. Future research should investigate the ability of juvenile Sea Lampreys to detect electric fields and their specific behavioral responses to electric field characteristics so as to optimize the use of this technology as a nonphysical guidance tool across variable water velocities.

A Novel Concept of Amino Acid Supplementation to Improve the Growth of Young Malnourished Male Rats.

PubMed

Furuta, Chie; Murakami, Hitoshi

2018-01-01

This study was aimed at understanding the relationship between plasma amino acids and protein malnutrition and at determining whether amino acid supplementation associated with malnutrition and growth improves linear growth in growing rats. Body length and plasma amino acids were measured in young male rats that were fed the following diet for 3 weeks, mimicking a low and imbalanced protein diets based on maize, a major staple consumed in developing countries: a 70% calorically restricted cornmeal-based diet (C), C + micronutrients (CM), CM + casein (CMC), CM + soy protein (CMS) or CMS + 0.3% lysine. A correlation analysis of linear growth and plasma amino acids indicated that lysine, tryptophan, branched-chain amino acids, methionine, and phenylalanine significantly correlated with body length. Supplementation with these 5 amino acids (AA1) significantly improved the body length in rats compared to CMC treatment whereas, nitrogen-balanced amino acid supplemented controls (AA2) did not (CM +1.2 ± 0.2, CMC +2.7 ± 0.3, CMS +2.1 ± 0.3, AA1 +2.8 ± 0.2, and AA2 +2.5 ± 0.3 cm). With securing proper amino acid balance, supplementing growth-related amino acids is more effective in improving linear growth in malnourished growing male rats. Analysis of the correlation between plasma amino acids and growth represents a powerful tool to determine candidate amino acids for supplementation to prevent malnutrition. This technology is adaptable to children in developing countries. © 2018 S. Karger AG, Basel.

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

An X-ray survey of nine historical novae. [HEAO 2 observations

NASA Technical Reports Server (NTRS)

Becker, R. H.; Marshall, F. E.

1980-01-01

The Einstein Observatory imaging proportional counter was used to search for X-ray emission from nine nearby historical novae. Six of the novae were detected with estimated X-ray intensities between .1 to 4 keV of 10 to the -13th power to 10 to the -11th power ergs/sq cm-s, comparable to the intensities of previously detected cataclysmic variables. The X-ray intensity of one of the novae, V603 Aql, varies over times of several hundred seconds. The data suggest a correlation between the decay rate of the historical outburst and the current X-ray luminosity. Alternatively, the X-ray luminosity may be related to the inclination of the binary system.

CMS proposal for interventional pain management by nurse anesthetists: evidence by proclamation with poor prognosis.

PubMed

Manchikanti, Laxmaiah; Caraway, David L; Falco, Frank J E; Benyamin, Ramsin M; Hansen, Hans; Hirsch, Joshua A

2012-01-01

The Office of Inspector General (OIG), Department of Health and Human Services (HHS), in a 2009 report, showed that unqualified nonphysicians performed 21% of the services. These nonphysicians did not possess the necessary licenses, certifications, credentials, or training to perform the services. Since the time the medical profession was founded, advances in treatments and technology, as well as educational and training standards, have promoted a desire to go beyond the basic scope of practice. Many have sought to broaden the scope of practice through legislative efforts and proclamation rather than education and training. In 2001, President Clinton signed into law a rule that permitted states to "opt out" of the Centers for Medicare and Medicaid Services' (CMS) requirement for nurse anesthetists to be supervised by any physician. Since then, 17 states have adopted this rule. While it was originally intended to help rural areas improve access to care, the opt out rule essentially supports any hospital or organization that seeks to make a profit or cut costs by allowing nurse anesthetists to function as physicians. With the implementation of sweeping health care regulations under the Affordable Care Act (ACA, also popularly known as Obamacare), the future of nurses and other professionals has been empowered. In fact, it has been proposed that medical training may be reduced by 30%, which will in their minds equalize training between nonphysicians and physicians. In 2010, the Federal Trade Commission (FTC) issued an opinion exerting their power to empower CRNAs with unlimited practice, with threats to opposing parties. In the 2013 proposed physician payment rule, CMS is proposing that CRNAs may perform interventional pain management services. Interventional pain management is a medical discipline with defined interventional techniques to be performed by professionals who are well trained and qualified. Without considering the consequences of the lack of education and training qualifications for CRNAs to offer interventional techniques, the FTC issued their opinion and CMS proposed to expand these practice patterns with a policy of improved access and reduced cost. However, in reality, the opposite will happen and will increase fraud, reduce access due to inappropriate procedures, and increase complications, all as a result of privileges by legislation without education. The CMS proposal for interventional pain management by nurse anesthetists is a proclamation with a poor prognosis.

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.

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.

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

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.

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

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.

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.

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.

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.

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.

Getting Started with Drupal WebCMS

EPA Pesticide Factsheets

Drupal WebCMS is accessible to EPA employees, and to onsite and offsite contractors. There are several roles in Drupal WebCMS and each allows a certain set of actions in the system. Users can have different roles in different web areas.

Preparing for Eclipse 2017 on This Week @NASA – August 11, 2017

NASA Image and Video Library

2017-08-11

The Aug. 21 total solar eclipse across America is generating a lot of interest – and a lot of questions. You’ll find answers to many of your eclipse questions at NASA’s Eclipse 2017 website -- eclipse2017.nasa.gov. The site is full of information to help you prepare for this rare celestial event – including eclipse-related activities, events, viewing safety tips, and other resources. Then, on the day of the eclipse, you can see the event “Through the Eyes of NASA” – during a special NASA TV broadcast that includes coast-to-coast coverage from the ground, from the air and from space. Coverage begins with a special pre-show at noon eastern – followed by in-depth coverage at 1pm. You can also watch on Aug. 21 at www.nasa.gov/eclipselive. Also, TDRS-M Update, Webb’s Sunshield Layers Installed, RS-25 Engine Testing Rolls On, and Chief Technologist Visits Industry Partner!

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.

Anti-aging effects of vitamin C on human pluripotent stem cell-derived cardiomyocytes.

PubMed

Kim, Yoon Young; Ku, Seung-Yup; Huh, Yul; Liu, Hung-Ching; Kim, Seok Hyun; Choi, Young Min; Moon, Shin Yong

2013-10-01

Human pluripotent stem cells (hPSCs) have arisen as a source of cells for biomedical research due to their developmental potential. Stem cells possess the promise of providing clinicians with novel treatments for disease as well as allowing researchers to generate human-specific cellular metabolism models. Aging is a natural process of living organisms, yet aging in human heart cells is difficult to study due to the ethical considerations regarding human experimentation as well as a current lack of alternative experimental models. hPSC-derived cardiomyocytes (CMs) bear a resemblance to human cardiac cells and thus hPSC-derived CMs are considered to be a viable alternative model to study human heart cell aging. In this study, we used hPSC-derived CMs as an in vitro aging model. We generated cardiomyocytes from hPSCs and demonstrated the process of aging in both human embryonic stem cell (hESC)- and induced pluripotent stem cell (hiPSC)-derived CMs. Aging in hESC-derived CMs correlated with reduced membrane potential in mitochondria, the accumulation of lipofuscin, a slower beating pattern, and the downregulation of human telomerase RNA (hTR) and cell cycle regulating genes. Interestingly, the expression of hTR in hiPSC-derived CMs was not significantly downregulated, unlike in hESC-derived CMs. In order to delay aging, vitamin C was added to the cultured CMs. When cells were treated with 100 μM of vitamin C for 48 h, anti-aging effects, specifically on the expression of telomere-related genes and their functionality in aging cells, were observed. Taken together, these results suggest that hPSC-derived CMs can be used as a unique human cardiomyocyte aging model in vitro and that vitamin C shows anti-aging effects in this model.

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.

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.

Automatic identification of bullet signatures based on consecutive matching striae (CMS) criteria.

PubMed

Chu, Wei; Thompson, Robert M; Song, John; Vorburger, Theodore V

2013-09-10

The consecutive matching striae (CMS) numeric criteria for firearm and toolmark identifications have been widely accepted by forensic examiners, although there have been questions concerning its observer subjectivity and limited statistical support. In this paper, based on signal processing and extraction, a model for the automatic and objective counting of CMS is proposed. The position and shape information of the striae on the bullet land is represented by a feature profile, which is used for determining the CMS number automatically. Rapid counting of CMS number provides a basis for ballistics correlations with large databases and further statistical and probability analysis. Experimental results in this report using bullets fired from ten consecutively manufactured barrels support this developed model. Published by Elsevier Ireland Ltd.

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.

Simulation of strong ground motion parameters of the 1 June 2013 Gulf of Suez earthquake, Egypt

NASA Astrophysics Data System (ADS)

Toni, Mostafa

2017-06-01

This article aims to simulate the ground motion parameters of the moderate magnitude (ML 5.1) June 1, 2013 Gulf of Suez earthquake, which represents the largest instrumental earthquake to be recorded in the middle part of the Gulf of Suez up to now. This event was felt in all cities located on both sides of the Gulf of Suez, with minor damage to property near the epicenter; however, no casualties were observed. The stochastic technique with the site-dependent spectral model is used to simulate the strong ground motion parameters of this earthquake in the cities located at the western side of the Gulf of Suez and north Red Sea namely: Suez, Ain Sokhna, Zafarana, Ras Gharib, and Hurghada. The presence of many tourist resorts and the increase in land use planning in the considered cities represent the motivation of the current study. The simulated parameters comprise the Peak Ground Acceleration (PGA), Peak Ground Velocity (PGV), and Peak Ground Displacement (PGD), in addition to Pseudo Spectral Acceleration (PSA). The model developed for ground motion simulation is validated by using the recordings of three accelerographs installed around the epicenter of the investigated earthquake. Depending on the site effect that has been determined in the investigated areas by using geotechnical data (e.g., shear wave velocities and microtremor recordings), the investigated areas are classified into two zones (A and B). Zone A is characterized by higher site amplification than Zone B. The ground motion parameters are simulated at each zone in the considered areas. The results reveal that the highest values of PGA, PGV, and PGD are observed at Ras Gharib city (epicentral distance ∼ 11 km) as 67 cm/s2, 2.53 cm/s, and 0.45 cm respectively for Zone A, and as 26.5 cm/s2, 1.0 cm/s, and 0.2 cm respectively for Zone B, while the lowest values of PGA, PGV, and PGD are observed at Suez city (epicentral distance ∼ 190 km) as 3.0 cm/s2, 0.2 cm/s, and 0.05 cm/s respectively for Zone A, and as 1.3 cm/s2, 0.1 cm/s, and 0.024 cm respectively for Zone B. Also the highest PSA values are observed in Ras Gharib city as 200 cm/s2 and 78 cm/s2 for Zone A and Zone B respectively, while the lowest PSA values are observed in Suez city as 7 cm/s2 and 3 cm/s2 for Zone A and Zone B respectively. These results show a good agreement with the earthquake magnitude, epicentral distances, and site characterizations as well.

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

Centaurus A /NGC 5128/ at 2 keV-2.3 MeV - HEAO 1 observations and implications

NASA Technical Reports Server (NTRS)

Baity, W. A.; Rothschild, R. E.; Lingenfelter, R. E.; Stein, W. A.; Nolan, P. L.; Gruber, D. E.; Knight, F. K.; Matteson, J. L.; Peterson, L. E.; Mushotzky, R. F.

1981-01-01

The active-nucleus galaxy Centaurus A has been studied at 2 keV-2.3 MeV using data from the UCSD/MIT hard X-ray and low-energy gamma-ray instrument and the GSFC/CIT cosmic X-ray experiment on HEAO-1. It is found that an E exp -1.60 + or - 0.03 power law spectrum breaking to E exp -2.0 + or - 0.2 at 140 keV best describes the January and July 1978 data. The average intensity was 50% higher during the January observations. Upper limits to unresolved lines at 511 keV and 1.6 MeV were found to be 6.5 x 10 to the -4th photons/sq cm-s and 2.2 x 10 to the -4th photons/sq cm-s, respectively, at the 90% confidence level. The present data are consistent with the detailed calculations of the synchrotron self-Compton mechanism; they may also agree, marginally, with the predictions of emission from spherical accretion onto black holes.

A browser-based event display for the CMS experiment at the LHC

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

Hategan, M.; McCauley, T.; Nguyen, P.

2012-01-01

The line between native and web applications is becoming increasingly blurred as modern web browsers are becoming powerful platforms on which applications can be run. Such applications are trivial to install and are readily extensible and easy to use. In an educational setting, web applications permit a way to deploy deploy tools in a highly-restrictive computing environment. The I2U2 collaboration has developed a browser-based event display for viewing events in data collected and released to the public by the CMS experiment at the LHC. The application itself reads a JSON event format and uses the JavaScript 3D rendering engine pre3d.more » The only requirement is a modern browser using HTML5 canvas. The event display has been used by thousands of high school students in the context of programs organized by I2U2, QuarkNet, and IPPOG. This browser-based approach to display of events can have broader usage and impact for experts and public alike.« less

iSpy: a powerful and lightweight event display

NASA Astrophysics Data System (ADS)

Alverson, G.; Eulisse, G.; McCauley, T.; Taylor, L.

2012-12-01

iSpy is a general-purpose event data and detector visualization program that was developed as an event display for the CMS experiment at the LHC and has seen use by the general public and teachers and students in the context of education and outreach. Central to the iSpy design philosophy is ease of installation, use, and extensibility. The application itself uses the open-access packages Qt4 and Open Inventor and is distributed either as a fully-bound executable or a standard installer package: one can simply download and double-click to begin. Mac OSX, Linux, and Windows are supported. iSpy renders the standard 2D, 3D, and tabular views, and the architecture allows for a generic approach to production of new views and projections. iSpy reads and displays data in the ig format: event information is written in compressed JSON format files designed for distribution over a network. This format is easily extensible and makes the iSpy client indifferent to the original input data source. The ig format is the one used for release of approved CMS data to the public.

Analysis and Quantification of Coupling Mechanisms of External Signal Perturbations on Silicon Detectors for Particle Physics Experiments

NASA Astrophysics Data System (ADS)

Arteche, F.; Rivetta, C.; Iglesias, M.; Echeverria, I.

2016-05-01

Silicon detectors have been used in astrophysics satellites and particle detectors for high energy physics (HEP) experiments. For HEP applications, EMC studies have been conducted in silicon detectors to characterize the impact of external noise on the system. They have shown that problems associated with the new generation of silicon detectors are related with interferences generated by the power supplies and auxiliary equipment connected to the device. Characterization of these interferences along with the coupling and their propagation into the susceptible front-end circuits is required for a successful integration of these systems. This paper presents the analysis of the sensitivity curves and coupling mechanisms between the noise and the front-end electronics that have been observed during the characterization of two silicon detector prototypes: the CMS-Silicon tracker detector (CMS-ST) and Silicon Vertex Detector (Belle II-SVD). As a result of these studies, it is possible to identify critical elements in prototypes to take corrective actions in the design and improve the front-end electronics performance.

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.

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

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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...

45 CFR 150.211 - Notice to the State.

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 § 150.211 Notice to the State. If CMS is...

42 CFR 422.157 - Accreditation organizations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... requirements or survey process. If the organization implements the changes before or without CMS approval, CMS... requirements and processes when— (i) CMS imposes new requirements or changes its survey process; (ii) An accreditation organization proposes to adopt new standards or changes in its survey process; or (iii) The term...

42 CFR 422.157 - Accreditation organizations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... requirements or survey process. If the organization implements the changes before or without CMS approval, CMS... requirements and processes when— (i) CMS imposes new requirements or changes its survey process; (ii) An accreditation organization proposes to adopt new standards or changes in its survey process; or (iii) The term...

42 CFR 422.157 - Accreditation organizations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... requirements or survey process. If the organization implements the changes before or without CMS approval, CMS... requirements and processes when— (i) CMS imposes new requirements or changes its survey process; (ii) An accreditation organization proposes to adopt new standards or changes in its survey process; or (iii) The term...

Flammability Aspects of a Cotton-Fiberglass Fabric in Opposed and Concurrent Airflow in Microgravity

NASA Technical Reports Server (NTRS)

Ferkul, Paul V.; Olson, Sandra; Johnston, Michael C.; T'ien, James

2012-01-01

Microgravity combustion tests burning fabric samples were performed aboard the International Space Station. The cotton-fiberglass blend samples were mounted inside a small wind tunnel which could impose air flow speeds up to 40 cm/s. The wind tunnel was installed in the Microgravity Science Glovebox which supplied power, imaging, and a level of containment. The effects of air flow speed on flame appearance, flame growth, and spread rates were determined in both the opposed and concurrent flow configuration. For the opposed flow configuration, the flame quickly reached steady spread for each flow speed, and the spread rate was fastest at an intermediate value of flow speed. These tests show the enhanced flammability in microgravity for this geometry, since, in normal gravity air, a flame self-extinguishes in the opposed flow geometry (downward flame spread). In the concurrent flow configuration, flame size grew with time during the tests. A limiting length and steady spread rate were obtained only in low flow speeds ( 10 cm/s) for the short-length samples that fit in the small wind tunnel. For these conditions, flame spread rate increased linearly with increasing flow. This is the first time that detailed transient flame growth data was obtained in purely forced flows in microgravity. In addition, by decreasing flow speed to a very low value (around 1 cm/s), quenching extinction was observed. The valuable results from these long-duration experiments validate a number of theoretical predictions and also provide the data for a transient flame growth model under development.

47 CFR 10.230 - New CMS providers participation in CMAS.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false New CMS providers participation in CMAS. 10.230 Section 10.230 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMERCIAL MOBILE ALERT SYSTEM Election to Participate in Commercial Mobile Alert System § 10.230 New CMS providers participation in CMAS...

42 CFR 401.719 - Monitoring and sanctioning of qualified entities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Data for Performance Measurement § 401.719 Monitoring and sanctioning of qualified entities. (a) CMS... methods: (1) Audits. (2) Submission of documentation of data sources and quantities of data upon the request of CMS and/or site visits. (3) Analysis of specific data reported to CMS by qualified entities...

76 FR 35444 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-17

... retrieval into the ASPEN system. The information needed to make certification decisions is available to CMS... Identifier CMS-1856 and CMS-1893] Agency Information Collection Activities: Submission for OMB Review... or any other aspect of this collection of information, including any of the following subjects: (1...

78 FR 42778 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-17

... transmissions: OMB, Office of Information and Regulatory Affairs, Attention: CMS Desk Officer, Fax Number: (202... Identifier: CMS-10494] 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...

78 FR 71617 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-29

... the following transmissions: OMB, Office of Information and Regulatory Affairs, Attention: CMS Desk... Identifier: CMS-R-194] 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...

78 FR 40482 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-05

... transmissions: OMB, Office of Information and Regulatory Affairs, Attention: CMS Desk Officer, Fax Number: (202... Identifier: CMS-10316] 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...

42 CFR 422.510 - Termination of contract by CMS.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) CMS notifies the MA organization in writing at least 45 calendar days before the intended date of the...; or (B) The MA organization experiences financial difficulties so severe that its ability to make...)(i) of this section. (ii) CMS notifies the MA organization in writing that its contract will be...

78 FR 39296 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-01

... & Medicaid Services (CMS) is announcing an opportunity for the public to comment on CMS' intention to collect information from the public. Under the Paperwork Reduction Act of 1995 (PRA), federal agencies are required to... Identifier: CMS-10486] Agency Information Collection Activities: Proposed Collection; Comment Request AGENCY...

42 CFR 493.573 - Continuing Federal oversight of private nonprofit accreditation organizations and approved State...

Code of Federal Regulations, 2010 CFR

2010-10-01

... sooner if CMS determines an earlier review is required. (b) Validation review. Following the end of a validation review period, CMS evaluates the validation inspection results for each approved accreditation... determined through a comparability or validation review, must furnish CMS, upon request, with the...

77 FR 52035 - Public Information Collection Requirements Submitted to the Office of Management and Budget (OMB...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-28

... Identifier: CMS-10003] Public Information Collection Requirements Submitted to the Office of Management and Budget (OMB); Correction AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Correction of notice. SUMMARY: This document corrects a technical error in the notice [Document Identifier: CMS...

45 CFR 150.309 - Request for extension.

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 With Respect to Issuers and Non-Federal... cannot prepare a response to CMS within the 30 days provided in the notice, the entity may make a written...

76 FR 33305 - Public Information Collection Requirements Submitted to the Office of Management and Budget (OMB...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-08

... Identifier: CMS-10379] Public Information Collection Requirements Submitted to the Office of Management and Budget (OMB); Correction AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Correction of notice. SUMMARY: This document corrects the information provided for [Document Identifier: CMS...

42 CFR 493.573 - Continuing Federal oversight of private nonprofit accreditation organizations and approved State...

Code of Federal Regulations, 2014 CFR

2014-10-01

... sooner if CMS determines an earlier review is required. (b) Validation review. Following the end of a validation review period, CMS evaluates the validation inspection results for each approved accreditation... determined through a comparability or validation review, must furnish CMS, upon request, with the...

42 CFR 493.573 - Continuing Federal oversight of private nonprofit accreditation organizations and approved State...

Code of Federal Regulations, 2013 CFR

2013-10-01

... sooner if CMS determines an earlier review is required. (b) Validation review. Following the end of a validation review period, CMS evaluates the validation inspection results for each approved accreditation... determined through a comparability or validation review, must furnish CMS, upon request, with the...

42 CFR 493.573 - Continuing Federal oversight of private nonprofit accreditation organizations and approved State...

Code of Federal Regulations, 2012 CFR

2012-10-01

... sooner if CMS determines an earlier review is required. (b) Validation review. Following the end of a validation review period, CMS evaluates the validation inspection results for each approved accreditation... determined through a comparability or validation review, must furnish CMS, upon request, with the...

42 CFR 493.573 - Continuing Federal oversight of private nonprofit accreditation organizations and approved State...

Code of Federal Regulations, 2011 CFR

2011-10-01

... sooner if CMS determines an earlier review is required. (b) Validation review. Following the end of a validation review period, CMS evaluates the validation inspection results for each approved accreditation... determined through a comparability or validation review, must furnish CMS, upon request, with the...

Ada (Tradename) Compiler Validation Summary Report. International Business Machines Corporation. IBM Development System for the Ada Language for VM/CMS, Version 1.0. IBM 4381 (IBM System/370) under VM/CMS.

DTIC Science & Technology

1986-04-29

COMPILER VALIDATION SUMMARY REPORT: International Business Machines Corporation IBM Development System for the Ada Language for VM/CMS, Version 1.0 IBM 4381...tested using command scripts provided by International Business Machines Corporation. These scripts were reviewed by the validation team. Test.s were run...s): IBM 4381 (System/370) Operating System: VM/CMS, release 3.6 International Business Machines Corporation has made no deliberate extensions to the

The CMS Data Analysis School Experience

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

De Filippis, N.; Bauerdick, L.; Chen, J.

The CMS Data Analysis School is an official event organized by the CMS Collaboration to teach students and post-docs how to perform a physics analysis. The school is coordinated by the CMS schools committee and was first implemented at the LHC Physics Center at Fermilab in 2010. As part of the training, there are a number of “short” exercises on physics object reconstruction and identification, Monte Carlo simulation, and statistical analysis, which are followed by “long” exercises based on physics analyses. Some of the long exercises go beyond the current state of the art of the corresponding CMS analyses. Thismore » paper describes the goals of the school, the preparations for a school, the structure of the training, and student satisfaction with the experience as measured by surveys.« less

The CMS data analysis school experience

NASA Astrophysics Data System (ADS)

De Filippis, N.; Bauerdick, L.; Chen, J.; Gallo, E.; Klima, B.; Malik, S.; Mulders, M.; Palla, F.; Rolandi, G.

2017-10-01

The CMS Data Analysis School is an official event organized by the CMS Collaboration to teach students and post-docs how to perform a physics analysis. The school is coordinated by the CMS schools committee and was first implemented at the LHC Physics Center at Fermilab in 2010. As part of the training, there are a number of “short” exercises on physics object reconstruction and identification, Monte Carlo simulation, and statistical analysis, which are followed by “long” exercises based on physics analyses. Some of the long exercises go beyond the current state of the art of the corresponding CMS analyses. This paper describes the goals of the school, the preparations for a school, the structure of the training, and student satisfaction with the experience as measured by surveys.

Cytoplasmic male sterility-associated chimeric open reading frames identified by mitochondrial genome sequencing of four Cajanus genotypes.

PubMed

Tuteja, Reetu; Saxena, Rachit K; Davila, Jaime; Shah, Trushar; Chen, Wenbin; Xiao, Yong-Li; Fan, Guangyi; Saxena, K B; Alverson, Andrew J; Spillane, Charles; Town, Christopher; Varshney, Rajeev K

2013-10-01

The hybrid pigeonpea (Cajanus cajan) breeding technology based on cytoplasmic male sterility (CMS) is currently unique among legumes and displays major potential for yield increase. CMS is defined as a condition in which a plant is unable to produce functional pollen grains. The novel chimeric open reading frames (ORFs) produced as a results of mitochondrial genome rearrangements are considered to be the main cause of CMS. To identify these CMS-related ORFs in pigeonpea, we sequenced the mitochondrial genomes of three C. cajan lines (the male-sterile line ICPA 2039, the maintainer line ICPB 2039, and the hybrid line ICPH 2433) and of the wild relative (Cajanus cajanifolius ICPW 29). A single, circular-mapping molecule of length 545.7 kb was assembled and annotated for the ICPA 2039 line. Sequence annotation predicted 51 genes, including 34 protein-coding and 17 RNA genes. Comparison of the mitochondrial genomes from different Cajanus genotypes identified 31 ORFs, which differ between lines within which CMS is present or absent. Among these chimeric ORFs, 13 were identified by comparison of the related male-sterile and maintainer lines. These ORFs display features that are known to trigger CMS in other plant species and to represent the most promising candidates for CMS-related mitochondrial rearrangements in pigeonpea.

Validation and Application of a Real-time PCR Protocol for the Specific Detection and Quantification of Clavibacter michiganensis subsp. sepedonicus in Potato.

PubMed

Cho, Min Seok; Park, Duck Hwan; Namgung, Min; Ahn, Tae-Young; Park, Dong Suk

2015-06-01

Clavibacter michiganensis subsp. sepedonicus (Cms) multiplies very rapidly, passing through the vascular strands and into the stems and petioles of a diseased potato. Therefore, the rapid and specific detection of this pathogen is highly important for the effective control of the pathogen. Although several PCR assays have been developed for detection, they cannot afford specific detection of Cms. Therefore, in this study, a computational genome analysis was performed to compare the sequenced genomes of the C. michiganensis subspecies and to identify an appropriate gene for the development of a subspecies-specific PCR primer set (Cms89F/R). The specificity of the primer set based on the putative phage-related protein was evaluated using genomic DNA from seven isolates of Cms and 27 other reference strains. The Cms89F/R primer set was more specific and sensitive than the existing assays in detecting Cms in in vitro using Cms cells and its genomic DNA. This assay was also able to detect at least 1.47×10(2) copies/μl of cloned-amplified target DNA, 5 fg of DNA using genomic DNA or 10(-6) dilution point of 0.12 at OD600 units of cells per reaction using a calibrated cell suspension.

Cytoplasmic Male Sterility-Associated Chimeric Open Reading Frames Identified by Mitochondrial Genome Sequencing of Four Cajanus Genotypes

PubMed Central

Tuteja, Reetu; Saxena, Rachit K.; Davila, Jaime; Shah, Trushar; Chen, Wenbin; Xiao, Yong-Li; Fan, Guangyi; Saxena, K. B.; Alverson, Andrew J.; Spillane, Charles; Town, Christopher; Varshney, Rajeev K.

2013-01-01

The hybrid pigeonpea (Cajanus cajan) breeding technology based on cytoplasmic male sterility (CMS) is currently unique among legumes and displays major potential for yield increase. CMS is defined as a condition in which a plant is unable to produce functional pollen grains. The novel chimeric open reading frames (ORFs) produced as a results of mitochondrial genome rearrangements are considered to be the main cause of CMS. To identify these CMS-related ORFs in pigeonpea, we sequenced the mitochondrial genomes of three C. cajan lines (the male-sterile line ICPA 2039, the maintainer line ICPB 2039, and the hybrid line ICPH 2433) and of the wild relative (Cajanus cajanifolius ICPW 29). A single, circular-mapping molecule of length 545.7 kb was assembled and annotated for the ICPA 2039 line. Sequence annotation predicted 51 genes, including 34 protein-coding and 17 RNA genes. Comparison of the mitochondrial genomes from different Cajanus genotypes identified 31 ORFs, which differ between lines within which CMS is present or absent. Among these chimeric ORFs, 13 were identified by comparison of the related male-sterile and maintainer lines. These ORFs display features that are known to trigger CMS in other plant species and to represent the most promising candidates for CMS-related mitochondrial rearrangements in pigeonpea. PMID:23792890

Validation and Application of a Real-time PCR Protocol for the Specific Detection and Quantification of Clavibacter michiganensis subsp. sepedonicus in Potato

PubMed Central

Cho, Min Seok; Park, Duck Hwan; Namgung, Min; Ahn, Tae-Young; Park, Dong Suk

2015-01-01

Clavibacter michiganensis subsp. sepedonicus (Cms) multiplies very rapidly, passing through the vascular strands and into the stems and petioles of a diseased potato. Therefore, the rapid and specific detection of this pathogen is highly important for the effective control of the pathogen. Although several PCR assays have been developed for detection, they cannot afford specific detection of Cms. Therefore, in this study, a computational genome analysis was performed to compare the sequenced genomes of the C. michiganensis subspecies and to identify an appropriate gene for the development of a subspecies-specific PCR primer set (Cms89F/R). The specificity of the primer set based on the putative phage-related protein was evaluated using genomic DNA from seven isolates of Cms and 27 other reference strains. The Cms89F/R primer set was more specific and sensitive than the existing assays in detecting Cms in in vitro using Cms cells and its genomic DNA. This assay was also able to detect at least 1.47×102 copies/μl of cloned-amplified target DNA, 5 fg of DNA using genomic DNA or 10−6 dilution point of 0.12 at OD600 units of cells per reaction using a calibrated cell suspension. PMID:26060431

Study familial hypertrophic cardiomyopathy using patient-specific induced pluripotent stem cells

PubMed Central

Han, Lu; Li, Yang; Tchao, Jason; Kaplan, Aaron D.; Lin, Bo; Li, You; Mich-Basso, Jocelyn; Lis, Agnieszka; Hassan, Narmeen; London, Barry; Bett, Glenna C.L.; Tobita, Kimimasa; Rasmusson, Randall L.; Yang, Lei

2014-01-01

Aims Familial hypertrophic cardiomyopathy (HCM) is one the most common heart disorders, with gene mutations in the cardiac sarcomere. Studying HCM with patient-specific induced pluripotent stem-cell (iPSC)-derived cardiomyocytes (CMs) would benefit the understanding of HCM mechanism, as well as the development of personalized therapeutic strategies. Methods and results To investigate the molecular mechanism underlying the abnormal CM functions in HCM, we derived iPSCs from an HCM patient with a single missense mutation (Arginine442Glycine) in the MYH7 gene. CMs were next enriched from HCM and healthy iPSCs, followed with whole transcriptome sequencing and pathway enrichment analysis. A widespread increase of genes responsible for ‘Cell Proliferation’ was observed in HCM iPSC-CMs when compared with control iPSC-CMs. Additionally, HCM iPSC-CMs exhibited disorganized sarcomeres and electrophysiological irregularities. Furthermore, disease phenotypes of HCM iPSC-CMs were attenuated with pharmaceutical treatments. Conclusion Overall, this study explored the possible patient-specific and mutation-specific disease mechanism of HCM, and demonstrates the potential of using HCM iPSC-CMs for future development of therapeutic strategies. Additionally, the whole methodology established in this study could be utilized to study mechanisms of other human-inherited heart diseases. PMID:25209314

Cardiomyopathy syndrome in Atlantic salmon Salmo salar L.: A review of the current state of knowledge.

PubMed

Garseth, Å H; Fritsvold, C; Svendsen, J C; Bang Jensen, B; Mikalsen, A B

2018-01-01

Cardiomyopathy syndrome (CMS) is a severe cardiac disease affecting Atlantic salmon Salmo salar L. The disease was first recognized in farmed Atlantic salmon in Norway in 1985 and subsequently in farmed salmon in the Faroe Islands, Scotland and Ireland. CMS has also been described in wild Atlantic salmon in Norway. The demonstration of CMS as a transmissible disease in 2009, and the subsequent detection and initial characterization of piscine myocarditis virus (PMCV) in 2010 and 2011 were significant discoveries that gave new impetus to the CMS research. In Norway, CMS usually causes mortality in large salmon in ongrowing and broodfish farms, resulting in reduced fish welfare, significant management-related challenges and substantial economic losses. The disease thus has a significant impact on the Atlantic salmon farming industry. There is a need to gain further basic knowledge about the virus, the disease and its epidemiology, but also applied knowledge from the industry to enable the generation and implementation of effective prevention and control measures. This review summarizes the currently available, scientific information on CMS and PMCV with special focus on epidemiology and factors influencing the development of CMS. © 2017 The Authors. Journal of Fish Diseases Published by John Wiley & Sons Ltd.

Gas separation performance of carbon molecular sieve membranes based on 6FDA-mPDA/DABA (3:2) polyimide.

PubMed

Qiu, Wulin; Zhang, Kuang; Li, Fuyue Stephanie; Zhang, Ke; Koros, William J

2014-04-01

6FDA-mPDA/DABA (3:2) polyimide was synthesized and characterized for uncross-linked, thermally crosslinked, and carbon molecular sieve (CMS) membranes. The membranes were characterized with thermogravimetric analysis, FTIR spectroscopy, wide-angle X-ray diffraction, and gas permeation tests. Variations in the d spacing, the formation of pore structures, and changes in the pore sizes of the CMS membranes were discussed in relation to pyrolysis protocols. The uncross-linked polymer membranes showed high CO2 /CH4 selectivity, whereas thermally crosslinked membranes exhibited significantly improved CO2 permeability and excellent CO2 plasticization resistance. The CMS membranes showed even higher CO2 permeability and CO2 /CH4 selectivity. An increase in the pyrolysis temperature resulted in CMS membranes with lower gas permeability but higher selectivity. The 550 °C pyrolyzed CMS membranes showed CO2 permeability as high as 14 750 Barrer with CO2 /CH4 selectivity of approximately 52. Even 800 °C pyrolyzed CMS membranes still showed high CO2 permeability of 2610 Barrer with high CO2 /CH4 selectivity of approximately 118. Both polymer membranes and the CMS membranes are very attractive in aggressive natural gas purification applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Effect of Divalent Cations on RED Performance and Cation Exchange Membrane Selection to Enhance Power Densities.

PubMed

Rijnaarts, Timon; Huerta, Elisa; van Baak, Willem; Nijmeijer, Kitty

2017-11-07

Reverse electrodialysis (RED) is a membrane-based renewable energy technology that can harvest energy from salinity gradients. The anticipated feed streams are natural river and seawater, both of which contain not only monovalent ions but also divalent ions. However, RED using feed streams containing divalent ions experiences lower power densities because of both uphill transport and increased membrane resistance. In this study, we investigate the effects of divalent cations (Mg 2+ and Ca 2+ ) on RED and demonstrate the mitigation of those effects using both novel and existing commercial cation exchange membranes (CEMs). Monovalent-selective Neosepta CMS is known to block divalent cations transport and can therefore mitigate reductions in stack voltage. The new multivalent-permeable Fuji T1 is able to transport divalent cations without a major increase in resistance. Both strategies significantly improve power densities compared to standard-grade CEMs when performing RED using streams containing divalent cations.

Evaluation of nefazodone-induced cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes

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

Lee, Sujeong, E-mail: crystalee@gmail.com; Lee, Hyang-Ae, E-mail: hyangaelee@gmail.com; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 110-799

2016-04-01

The recent establishment of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), which express the major cardiac ion channels and recapitulate spontaneous mechanical and electrical activities, may provide a possible solution for the lack of in vitro human-based cardiotoxicity testing models. Cardiotoxicity induced by the antidepressant nefazodone was previously revealed to cause an acquired QT prolongation by hERG channel blockade. To elucidate the cellular mechanisms underlying the cardiotoxicity of nefazodone beyond hERG, its effects on cardiac action potentials (APs) and ion channels were investigated using hiPSC-CMs with whole-cell patch clamp techniques. In a proof of principle study, we examined the effectsmore » of cardioactive channel blockers on the electrophysiological profile of hiPSC-CMs in advance of the evaluation of nefazodone. Nefazodone dose-dependently prolonged the AP duration at 90% (APD{sub 90}) and 50% (APD{sub 50}) repolarization, reduced the maximum upstroke velocity (dV/dt{sub max}) and induced early after depolarizations. Voltage-clamp studies of hiPSC-CMs revealed that nefazodone inhibited various voltage-gated ion channel currents including I{sub Kr}, I{sub Ks}, I{sub Na}, and I{sub Ca}. Among them, I{sub Kr} and I{sub Na} showed relatively higher sensitivity to nefazodone, consistent with the changes in the AP parameters. In summary, hiPSC-CMs enabled an integrated approach to evaluate the complex interactions of nefazodone with cardiac ion channels. These results suggest that hiPSC-CMs can be an effective model for detecting drug-induced arrhythmogenicity beyond the current standard assay of heterologously expressed hERG K{sup +} channels. - Highlights: • Nefazodone prolonged APD and decreased upstroke velocity of APs in hiPSC-CMs. • Nefazodone inhibited cardiac ion channels, especially I{sub Kr} and I{sub Na}, in hiPSC-CMs. • Nefazodone-induced AP changes are mainly the result of I{sub Kr} and I{sub Na} inhibition. • hiPSC-CMs are sensitive model to validate nefazodone-induced cardiotoxicity. • hiPSC-CMs provide an integrated approach for evaluating mechanism of drug actions.« less

Toward Personalized Medicine: Using Cardiomyocytes Differentiated From Urine-Derived Pluripotent Stem Cells to Recapitulate Electrophysiological Characteristics of Type 2 Long QT Syndrome.

PubMed

Jouni, Mariam; Si-Tayeb, Karim; Es-Salah-Lamoureux, Zeineb; Latypova, Xenia; Champon, Benoite; Caillaud, Amandine; Rungoat, Anais; Charpentier, Flavien; Loussouarn, Gildas; Baró, Isabelle; Zibara, Kazem; Lemarchand, Patricia; Gaborit, Nathalie

2015-09-01

Human genetically inherited cardiac diseases have been studied mainly in heterologous systems or animal models, independent of patients' genetic backgrounds. Because sources of human cardiomyocytes (CMs) are extremely limited, the use of urine samples to generate induced pluripotent stem cell-derived CMs would be a noninvasive method to identify cardiac dysfunctions that lead to pathologies within patients' specific genetic backgrounds. The objective was to validate the use of CMs differentiated from urine-derived human induced pluripotent stem (UhiPS) cells as a new cellular model for studying patients' specific arrhythmia mechanisms. Cells obtained from urine samples of a patient with long QT syndrome who harbored the HERG A561P gene mutation and his asymptomatic noncarrier mother were reprogrammed using the episomal-based method. UhiPS cells were then differentiated into CMs using the matrix sandwich method.UhiPS-CMs showed proper expression of atrial and ventricular myofilament proteins and ion channels. They were electrically functional, with nodal-, atrial- and ventricular-like action potentials recorded using high-throughput optical and patch-clamp techniques. Comparison of HERG expression from the patient's UhiPS-CMs to the mother's UhiPS-CMs showed that the mutation led to a trafficking defect that resulted in reduced delayed rectifier K(+) current (IKr). This phenotype gave rise to action potential prolongation and arrhythmias. UhiPS cells from patients carrying ion channel mutations can be used as novel tools to differentiate functional CMs that recapitulate cardiac arrhythmia phenotypes. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Congenital myasthenic syndrome with tubular aggregates caused by GFPT1 mutations.

PubMed

Guergueltcheva, Velina; Müller, Juliane S; Dusl, Marina; Senderek, Jan; Oldfors, Anders; Lindbergh, Christopher; Maxwell, Susan; Colomer, Jaume; Mallebrera, Cecilia Jimenez; Nascimento, Andres; Vilchez, Juan J; Muelas, Nuria; Kirschner, Janbernd; Nafissi, Shahriar; Kariminejad, Ariana; Nilipour, Yalda; Bozorgmehr, Bita; Najmabadi, Hossein; Rodolico, Carmelo; Sieb, Jörn P; Schlotter, Beate; Schoser, Benedikt; Herrmann, Ralf; Voit, Thomas; Steinlein, Ortrud K; Najafi, Abdolhamid; Urtizberea, Andoni; Soler, Doriette M; Muntoni, Francesco; Hanna, Michael G; Chaouch, Amina; Straub, Volker; Bushby, Kate; Palace, Jacqueline; Beeson, David; Abicht, Angela; Lochmüller, Hanns

2012-05-01

Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of inherited disorders of the neuromuscular junction. A difficult to diagnose subgroup of CMS is characterised by proximal muscle weakness and fatigue while ocular and facial involvement is only minimal. DOK7 mutations have been identified as causing the disorder in about half of the cases. More recently, using classical positional cloning, we have identified mutations in a previously unrecognised CMS gene, GFPT1, in a series of DOK7-negative cases. However, detailed description of clinical features of GFPT1 patients has not been reported yet. Here we describe the clinical picture of 24 limb-girdle CMS (LG-CMS) patients and pathological findings of 18 of them, all carrying GFPT1 mutations. Additional patients with CMS, but without tubular aggregates, and patients with non-fatigable weakness with tubular aggregates were also screened. In most patients with GFPT1 mutations, onset of the disease occurs in the first decade of life with characteristic limb-girdle weakness and fatigue. A common feature was beneficial and sustained response to acetylcholinesterase inhibitor treatment. Most of the patients who had a muscle biopsy showed tubular aggregates in myofibers. Analysis of endplate morphology in one of the patients revealed unspecific abnormalities. Our study delineates the phenotype of CMS associated with GFPT1 mutations and expands the understanding of neuromuscular junction disorders. As tubular aggregates in context of a neuromuscular transmission defect appear to be highly indicative, we suggest calling this condition congenital myasthenic syndrome with tubular aggregates (CMS-TA).

The Church Mountain Sturzstrom (Mega-Landslide), Glacier, Washington

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

Carpenter, M.R.; Easterbrook, D.J.

1993-04-01

Detailed investigation of an ancient sturzstrom or mega-landslide near Glacier, Washington has revealed it areal extent, approximate volume, age, geomorphology, source area, and possible causes. Stratigraphic and lithologic investigations indicate Church Mountain as the source area; therefore, this mega-landslide has been named the Church Mountain Sturzstrom (CMS). The CMS deposit is approximately 9 km in length, averages about 1 km in width, and has an estimated volume of 3 [times] 10[sup 8] m[sup 3]. Characteristics of the morphology and stratigraphy of the CMS deposit are suggestive of a sturzstrom origin, and may be indicative of sturzstrom elsewhere in the world.more » The overall stratigraphy of the deposit mimics the stratigraphy of the source area. The deposit is very compact, poorly sorted, matrix supported, and composed of highly angular clasts. Over steepening of the mountain due to glacial erosion may have contributed to the cause of failure, although the age of the CMS is at least 7,000 years younger than deglaciation. Four trees were C[sup 14] dated, yielding ages of about 2,700 B.P. for the CMS. Several other mega-landslides have been identified within 5--30 km of the CMS. The close proximity of these mega-landslides to the CMS suggests the possibility that they may have been triggered by an earthquake, although the ages of the other slides are currently unknown. The age of the CMS correlates approximately with age ranges of co-seismic events occurring along the west coast of Washington, further suggesting the possibility of an earthquake triggering mechanism.« less

Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study.

PubMed

Cadby, Gemma; Melton, Phillip E; McCarthy, Nina S; Almeida, Marcio; Williams-Blangero, Sarah; Curran, Joanne E; VandeBerg, John L; Hui, Jennie; Beilby, John; Musk, A W; James, Alan L; Hung, Joseph; Blangero, John; Moses, Eric K

2018-01-01

Over two billion adults are overweight or obese and therefore at an increased risk of cardiometabolic syndrome (CMS). Obesity-related anthropometric traits genetically correlated with CMS may provide insight into CMS aetiology. The aim of this study was to utilise an empirically derived genetic relatedness matrix to calculate heritabilities and genetic correlations between CMS and anthropometric traits to determine whether they share genetic risk factors (pleiotropy). We used genome-wide single nucleotide polymorphism (SNP) data on 4671 Busselton Health Study participants. Exploiting both known and unknown relatedness, empirical kinship probabilities were estimated using these SNP data. General linear mixed models implemented in SOLAR were used to estimate narrow-sense heritabilities (h 2 ) and genetic correlations (r g ) between 15 anthropometric and 9 CMS traits. Anthropometric traits were adjusted by body mass index (BMI) to determine whether the observed genetic correlation was independent of obesity. After adjustment for multiple testing, all CMS and anthropometric traits were significantly heritable (h 2 range 0.18-0.57). We identified 50 significant genetic correlations (r g range: - 0.37 to 0.75) between CMS and anthropometric traits. Five genetic correlations remained significant after adjustment for BMI [high density lipoprotein cholesterol (HDL-C) and waist-hip ratio; triglycerides and waist-hip ratio; triglycerides and waist-height ratio; non-HDL-C and waist-height ratio; insulin and iliac skinfold thickness]. This study provides evidence for the presence of potentially pleiotropic genes that affect both anthropometric and CMS traits, independently of obesity.

Patch-Clamp Recording from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Improving Action Potential Characteristics through Dynamic Clamp

PubMed Central

Veerman, Christiaan C.; Zegers, Jan G.; Mengarelli, Isabella; Bezzina, Connie R.

2017-01-01

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for studying inherited cardiac arrhythmias and developing drug therapies to treat such arrhythmias. Unfortunately, until now, action potential (AP) measurements in hiPSC-CMs have been hampered by the virtual absence of the inward rectifier potassium current (IK1) in hiPSC-CMs, resulting in spontaneous activity and altered function of various depolarising and repolarising membrane currents. We assessed whether AP measurements in “ventricular-like” and “atrial-like” hiPSC-CMs could be improved through a simple, highly reproducible dynamic clamp approach to provide these cells with a substantial IK1 (computed in real time according to the actual membrane potential and injected through the patch-clamp pipette). APs were measured at 1 Hz using perforated patch-clamp methodology, both in control cells and in cells treated with all-trans retinoic acid (RA) during the differentiation process to increase the number of cells with atrial-like APs. RA-treated hiPSC-CMs displayed shorter APs than control hiPSC-CMs and this phenotype became more prominent upon addition of synthetic IK1 through dynamic clamp. Furthermore, the variability of several AP parameters decreased upon IK1 injection. Computer simulations with models of ventricular-like and atrial-like hiPSC-CMs demonstrated the importance of selecting an appropriate synthetic IK1. In conclusion, the dynamic clamp-based approach of IK1 injection has broad applicability for detailed AP measurements in hiPSC-CMs. PMID:28867785

Combinatorial Polymer Matrices Enhance In Vitro Maturation of Human Induced Pluripotent Cell Cell-Derived Cardiomyocytes

PubMed Central

Chun, Young Wook; Balikov, Daniel A.; Feaster, Tromondae K.; Williams, Charles H.; Sheng, Calvin C.; Lee, Jung-Bok; Boire, Timothy C.; Neely, M. Diana; Bellan, Leon M.; Ess, Kevin C.; Bowman, Aaron B.; Sung, Hak-Joon; Hong, Charles C.

2015-01-01

Cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CMs) hold great promise for modeling human heart diseases. However, iPSC-CMs studied to date resemble immature embryonic myocytes and therefore do not adequately recapitulate native adult cardiomyocyte phenotypes. Since extracellular matrix plays an essential role in heart development and maturation in vivo, we sought to develop a synthetic culture matrix that could enhance functional maturation of iPSC-CMs in vitro. In this study, we employed a library of combinatorial polymers comprising of three functional subunits - poly-ε-caprolacton (PCL), polyethylene glycol (PEG), and carboxylated PCL (cPCL) - as synthetic substrates for culturing human iPSC-CMs. Of these, iPSC-CMs cultured on 4%PEG-96%PCL (each % indicates the corresponding molar ratio) exhibit the greatest contractility and mitochondrial function. These functional enhancements are associated with increased expression of cardiac myosin light chain-2v, cardiac troponin I and integrin alpha-7. Importantly, iPSC-CMs cultured on 4%PEG-95%PCL demonstrate troponin I (TnI) isoform switch from the fetal slow skeletal TnI (ssTnI) to the postnatal cardiac TnI (cTnI), the first report of such transition in vitro. Finally, culturing iPSC-CMs on 4%PEG-96%PCL also significantly increased expression of genes encoding intermediate filaments known to transduce integrin-mediated mechanical signals to the myofilaments. In summary, our study demonstrates that synthetic culture matrices engineered from combinatorial polymers can be utilized to promote in vitro maturation of human iPSC-CMs through the engagement of critical matrix-integrin interactions. PMID:26204225

Population Pharmacokinetics of Colistin Methanesulfonate in Rats: Achieving Sustained Lung Concentrations of Colistin for Targeting Respiratory Infections

PubMed Central

W. S. Yapa, Shalini; Li, Jian; Porter, Christopher J. H.; Nation, Roger L.

2013-01-01

Colistin methanesulfonate (CMS), the inactive prodrug of colistin, is administered by inhalation for the management of respiratory infections. However, limited pharmacokinetic data are available for CMS and colistin following pulmonary delivery. This study investigates the pharmacokinetics of CMS and colistin following intravenous (i.v.) and intratracheal (i.t.) administration in rats and determines the targeting advantage after direct delivery into the lungs. In addition to plasma, bronchoalveolar lavage (BAL) fluid was collected to quantify drug concentrations in lung epithelial lining fluid (ELF). The resulting data were analyzed using a population modeling approach in S-ADAPT. A three-compartment model described the disposition of both compounds in plasma following i.v. administration. The estimated mean clearance from the central compartment was 0.122 liters/h for CMS and 0.0657 liters/h for colistin. Conversion of CMS to colistin from all three compartments was required to fit the plasma data. The fraction of the i.v. dose converted to colistin in the systemic circulation was 0.0255. Two BAL fluid compartments were required to reflect drug kinetics in the ELF after i.t. dosing. A slow conversion of CMS (mean conversion time [MCTCMS] = 3.48 h) in the lungs contributed to high and sustained concentrations of colistin in ELF. The fraction of the CMS dose converted to colistin in ELF (fm,ELF = 0.226) was higher than the corresponding fractional conversion in plasma after i.v. administration. In conclusion, pulmonary administration of CMS achieves high and sustained exposures of colistin in lungs for targeting respiratory infections. PMID:23917323

Stability of Colistin and Colistin Methanesulfonate in Aqueous Media and Plasma as Determined by High-Performance Liquid Chromatography

PubMed Central

Li, Jian; Milne, Robert W.; Nation, Roger L.; Turnidge, John D.; Coulthard, Kingsley

2003-01-01

The stabilities of colistin and colistin methanesulfonate (CMS) in different aqueous media were studied by specific high-performance liquid chromatography (HPLC) methods. Colistin was stable in water at 4 and 37°C for up to 60 days and 120 h, respectively. However, degradation was observed when colistin was stored in isotonic phosphate buffer (0.067 M, pH 7.4) and human plasma at 37°C. The stability of CMS from three different sources in water was explored by strong-anion-exchange (SAX) HPLC for CMS and by measuring the concentrations of colistin formed from the hydrolysis of CMS. The peaks of CMS in SAX HPLC disappeared almost completely after 12 h at 37°C, but appeared to remain intact for up to 2 days at 4°C. Over the same period, there was no formation of colistin at 4°C. In water, phosphate buffer, and plasma, there was rapid formation of colistin within 24 to 48 h at 37°C from the three sources of CMS. The hydrolysis products were assumed to be a complex mixture of many different sulfomethyl derivatives, including colistin. The stability of a fourth source of CMS in Mueller-Hinton broth examined during 30 min at 37°C revealed no formation of colistin. Along with previous microbiological studies, this suggested that different sulfomethyl CMSs possess intrinsic antibacterial activity. These results will be helpful for understanding the pharmacokinetics and pharmacodynamics of colistin and CMS in humans and animals. PMID:12654671

42 CFR 457.150 - CMS review of State plan material.

Code of Federal Regulations, 2013 CFR

2013-10-01

... State plan material. (a) Basis for action. CMS reviews each State plan and plan amendment to determine... on complete plan. CMS approves or disapproves the State plan or plan amendment only in its entirety... disapprove the State plan or plan amendment, or to determine that previously approved material no longer...

Status and commissioning of the CMS experiment

NASA Astrophysics Data System (ADS)

Wulz, C.-E.

2008-05-01

The construction status of the CMS experiment at the Large Hadron Collider and strategies for commissioning the subdetectors, the magnet, the trigger and the data acquisition are described. The first operations of CMS as a unified system, using either cosmic rays or test data, and the planned activities until the startup of the LHC are presented.

42 CFR 457.150 - CMS review of State plan material.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SERVICES (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES Introduction; State Plans for Child Health Insurance Programs and Outreach Strategies § 457.150 CMS review of... 42 Public Health 4 2010-10-01 2010-10-01 false CMS review of State plan material. 457.150 Section...

76 FR 24034 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-29

... discussed at workgroup meetings. In turn, CMS' HCPCS workgroup reaches a decision as to whether a change... Level II Codes. As a result, the National Panel was delineated and CMS continued with the decision-making process under its current structure, the CMS HCPCS Workgroup (herein referred to as ``the...

78 FR 41931 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-12

...). CMS-2746 End Stage Renal Disease Death Notification CMS-2728 End Stage Renal Disease Medical Evidence...: End Stage Renal Disease Death Notification; Use: The End Stage Renal Disease (ESRD) Death Notification (CMS-2746) is completed by all Medicare-approved ESRD facilities upon the death of an ESRD patient. Its...

42 CFR 422.308 - Adjustments to capitation rates, benchmarks, bids, and payments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... equivalence. CMS may add to, modify, or substitute for risk adjustment factors if those changes will improve... adjust for health status, CMS applies a risk factor based on data obtained in accordance with § 422.310. (ii) Implementation. CMS applies a risk factor that incorporates inpatient hospital and ambulatory...

76 FR 55917 - Medicare Program; Notification of Closure of St. Vincent's Medical Center; Extension of the...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare & Medicaid Services [CMS-1587-N2... Submission of Applications AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Notice of... hospitals to apply to the Centers for Medicare & Medicaid Services (CMS) to receive St. Vincent's Medical...

Interspecific amphiploid-derived alloplasmic male sterility with defective anthers, narrow disk florets, and small ray flowers in sunflower

USDA-ARS?s Scientific Manuscript database

The cytoplasmic male-sterility (CMS)/fertility-restoration system is important for hybrid sunflower (Helianthus annuus L.) seed production. Two novel alloplasmic CMSs, designated CMS GRO1 and CMS MAX3 with defective anthers, narrow disk florets with no swollen corolla, and short, narrow ray flowers,...

77 FR 59616 - Medicare and Medicaid Programs; Approval of the American Osteopathic Association/Healthcare...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare & Medicaid Services [CMS-3264-FN... Accreditation Program (AOA/HFAP) Application for Continuing CMS-Approval of Its Ambulatory Surgical Center (ASC... 6 years or sooner as determined by CMS. AOA/HFAP's current term of approval for their ASC...

78 FR 57857 - Medicare and Medicaid Programs; Application from the Compliance Team for Initial CMS-Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-20

...] Medicare and Medicaid Programs; Application from the Compliance Team for Initial CMS-Approval of its Rural... Compliance Team for initial recognition as a national accrediting organization for rural health clinics (RHCs... Compliance Team's request for initial CMS approval of its RHC accreditation program. This notice also...

Training ELF Teachers to Create a Blended Learning Environment: Encouraging CMS Adoption and Implementation

ERIC Educational Resources Information Center

Cote, Travis; Milliner, Brett

2015-01-01

E-learning has become a crucial component of most tertiary institution's education initiatives (Park, Lee, & Cheong, 2007) and core to most e-learning strategies is the institution's Content Management System (CMS). A CMS has the potential to enhance language courses by facilitating engagement with class content, providing students with…

Health economics perspective of the components of the cardiometabolic syndrome.

PubMed

Tamariz, Leonardo; Palacio, Ana; Yang, Yadong; Parris, Donald; Ben-Joseph, Rami; Florez, Hermes

2010-07-01

The components of the cardiometabolic syndrome (CMS) increase the risk of coronary artery disease (CAD). The authors compared 12-month costs of subjects with different number of components of the CMS. In claims data from a large health benefits company, 383,420 individuals with the first International Classification of Diseases, Ninth Revision codes for hypertension, diabetes, lipid abnormalities, and obesity were identified. Patients were stratified according to presence of CAD and the number of components of the CMS. Twelve-month costs were added after the identification of the risk factor. Mean annual costs increased with the number of components of CMS both in those with and without CAD, even after adjusting for age, sex, and comorbidities (P<.01). Similar trends were seen for medical and pharmacy costs. The adjusted total annual health care cost in those with an isolated component of the CMS was $5564 (95% confidence interval: $5491-$5631) while in those with 4 components was $12,287 (95% confidence interval: $11,987-$12,587). Individuals with accumulating components of the CMS have higher health care costs regardless of age, sex, and other comorbidities.

Human pluripotent stem cell-derived cardiomyocytes for heart regeneration, drug discovery and disease modeling: from the genetic, epigenetic, and tissue modeling perspectives.

PubMed

Chow, Maggie; Boheler, Kenneth R; Li, Ronald A

2013-08-14

Heart diseases remain a major cause of mortality and morbidity worldwide. However, terminally differentiated human adult cardiomyocytes (CMs) possess a very limited innate ability to regenerate. Directed differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) into CMs has enabled clinicians and researchers to pursue the novel therapeutic paradigm of cell-based cardiac regeneration. In addition to tissue engineering and transplantation studies, the need for functional CMs has also prompted researchers to explore molecular pathways and develop strategies to improve the quality, purity and quantity of hESC-derived and iPSC-derived CMs. In this review, we describe various approaches in directed CM differentiation and driven maturation, and discuss potential limitations associated with hESCs and iPSCs, with an emphasis on the role of epigenetic regulation and chromatin remodeling, in the context of the potential and challenges of using hESC-CMs and iPSC-CMs for drug discovery and toxicity screening, disease modeling, and clinical applications.

Challenging data and workload management in CMS Computing with network-aware systems

NASA Astrophysics Data System (ADS)

D, Bonacorsi; T, Wildish

2014-06-01

After a successful first run at the LHC, and during the Long Shutdown (LS1) of the accelerator, the workload and data management sectors of the CMS Computing Model are entering into an operational review phase in order to concretely assess area of possible improvements and paths to exploit new promising technology trends. In particular, since the preparation activities for the LHC start, the Networks have constantly been of paramount importance for the execution of CMS workflows, exceeding the original expectations - as from the MONARC model - in terms of performance, stability and reliability. The low-latency transfers of PetaBytes of CMS data among dozens of WLCG Tiers worldwide using the PhEDEx dataset replication system is an example of the importance of reliable Networks. Another example is the exploitation of WAN data access over data federations in CMS. A new emerging area of work is the exploitation of Intelligent Network Services, including also bandwidth on demand concepts. In this paper, we will review the work done in CMS on this, and the next steps.

CMS issues updated rules for the Medicare claims appeal process.

PubMed

Davidson, Nancy J

2003-01-01

BIPA requires extensive changes to Medicare's appeal process. However, due to the lack of funding and adequate resources, CMS has been unable to immediately implement many of BIPA's far-reaching changes. CMS is committed to making a transition to the new process as quickly as possible and intends to implement as many key issues as feasible within budget and resource limits. Once Congress allocates funds for the new changes, CMS will be in a better position to implement all aspects of BIPA. [table: see text] The most significant change that BIPA presents is that Congress will require 12 new contractors to handle Part A and Part B appeals. These entities will be known as qualified independent contractors (QICs). CMS has completed development of the requests for proposals needed to solicit bids for the QIC contracts, including full statements of the scope of work (SOW) for these contracts. CMS released the draft SOW on Oct. 7, 2002. It is anticipated that the addition of the QICs will provide a more uniform and consistent handling of Medicare appeals on a national level.

Self-assembly behaviour of colistin and its prodrug colistin methanesulfonate: implications for solution stability and solubilization

PubMed Central

Wallace, Stephanie J.; Li, Jian; Nation, Roger L.; Prankerd, Richard J.; Velkov, Tony; Boyd, Ben J.

2010-01-01

Colistin is an amphiphilic antibiotic that has re-emerged into clinical use due to the increasing prevalence of difficult-to-treat Gram-negative infections. The existence of self-assembling colloids in solutions of colistin and its derivative prodrug, colistin methanesulfonate (CMS) was investigated. Colistin and CMS reduced the air-water interfacial tension, and dynamic light scattering (DLS) studies showed the existence of 2.07 ± 0.3 nm aggregates above 1.5 mM for colistin, and of 1.98 ± 0.36 nm aggregates for CMS above 3.5 mM (mean ± SD). Above the respective critical micelle concentrations (CMC) the solubility of azithromycin, a hydrophobic antibiotic, increased approximately linearly with increasing surfactant concentration (5:1 mol ratio colistin:azithromycin), suggestive of hydrophobic domains within the micellar cores. Rapid conversion of CMS to colistin occurred below the CMC (60 % over 48 hr), while conversion above the CMC was less than 1 %. The formation of colistin and CMS micelles demonstrated in this study is the proposed mechanism for solubilization of azithromycin and the concentration-dependent stability of CMS. PMID:20302384

The Archive Solution for Distributed Workflow Management Agents of the CMS Experiment at LHC

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

Kuznetsov, Valentin; Fischer, Nils Leif; Guo, Yuyi

The CMS experiment at the CERN LHC developed the Workflow Management Archive system to persistently store unstructured framework job report documents produced by distributed workflow management agents. In this paper we present its architecture, implementation, deployment, and integration with the CMS and CERN computing infrastructures, such as central HDFS and Hadoop Spark cluster. The system leverages modern technologies such as a document oriented database and the Hadoop eco-system to provide the necessary flexibility to reliably process, store, and aggregatemore » $$\\mathcal{O}$$(1M) documents on a daily basis. We describe the data transformation, the short and long term storage layers, the query language, along with the aggregation pipeline developed to visualize various performance metrics to assist CMS data operators in assessing the performance of the CMS computing system.« less

The Archive Solution for Distributed Workflow Management Agents of the CMS Experiment at LHC

DOE PAGES

Kuznetsov, Valentin; Fischer, Nils Leif; Guo, Yuyi

2018-03-19

The CMS experiment at the CERN LHC developed the Workflow Management Archive system to persistently store unstructured framework job report documents produced by distributed workflow management agents. In this paper we present its architecture, implementation, deployment, and integration with the CMS and CERN computing infrastructures, such as central HDFS and Hadoop Spark cluster. The system leverages modern technologies such as a document oriented database and the Hadoop eco-system to provide the necessary flexibility to reliably process, store, and aggregatemore » $$\\mathcal{O}$$(1M) documents on a daily basis. We describe the data transformation, the short and long term storage layers, the query language, along with the aggregation pipeline developed to visualize various performance metrics to assist CMS data operators in assessing the performance of the CMS computing system.« less

Carboxymethyl starch/montmorillonite composite microparticles: Properties and controlled release of isoproturon.

PubMed

Wilpiszewska, Katarzyna; Spychaj, Tadeusz; Paździoch, Waldemar

2016-01-20

Preparation of novel high substituted carboxymethyl starch-based microparticles containing sodium montmorillonite (MMT) by crosslinking with Al(3+) was described. For preparing nanocomposite granules carboxymethyl starch (CMS) from native potato starch as well as CMS from amylopectin has been used. The hydrophilic CMS/MMT composite systems were used for herbicide, i.e. isoproturon encapsulation (ca. 75% encapsulation efficiency). The herbicide release rate from CMS/MMT composites in water was significantly reduced when compared to commercial isoproturon: 95% released after ca. 700 h and ca. 24h, respectively. Leaching in soil from composite systems was relatively slower than release in water. After a series of eight irrigations leached about 10% of isoproturon loaded. The CMS/MMT carriers could reduce the potential leaching of herbicide and beneficially reduce pollution of the environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

A model of determining a fair market value for teaching residents: who profits?

PubMed

Cullen, Edward J; Lawless, Stephen T; Hertzog, James H; Penfil, Scott; Bradford, Kathleen K; Nadkarni, Vinay M; Corddry, David H; Costarino, Andrew T

2003-07-01

Centers for Medicare & Medicaid Services (CMS) Health Resources and Services Administration Children's Hospitals Graduate Medical Education (GME) Payment Program now supports freestanding children's teaching hospitals. To analyze the fair market value impact of GME payment on resident teaching efforts in our pediatric intensive care unit (PICU). Cost-accounting model, developed from a 1-year retrospective, descriptive, single-institution, longitudinal study, applied to physician teachers, residents, and CMS. Sixteen-bed PICU in a freestanding, university-affiliated children's teaching hospital. Pediatric critical care physicians, second-year residents. Cost of physician opportunity time; CMS investment return; the teaching physicians' investment return; residents' investment return; service balance between CMS and teaching service investment margins; economic balance points; fair market value. GME payments to our hospital increased 4.8-fold from 577 886 dollars to 2 772 606 dollars during a 1-year period. Critical care physicians' teaching opportunity cost rose from 250 097 dollars to 262 215 dollars to provide 1523 educational hours (6853 relative value units). Residents' net financial value for service provided to the PICU rose from 245 964 dollars to 317 299 dollars. There is an uneven return on investment in resident education for CMS, critical care physicians, and residents. Economic balance points are achievable for the present educational efforts of the CMS, critical care physicians, and residents if the present direct medical education payment increases from 29.38% to 36%. The current CMS Health Resources and Services Administration Children's Hospitals GME Payment Program produces uneven investment returns for CMS, critical care physicians, and residents. We propose a cost-accounting model, based on perceived production capability measured in relative value units and available GME funds, that would allow a clinical service to balance and obtain a fair market value for the resident education efforts of CMS, physician teachers, and residents.

Plasma soluble erythropoietin receptor is decreased during sleep in Andean highlanders with Chronic Mountain Sickness.

PubMed

Villafuerte, Francisco C; Corante, Noemí; Anza-Ramírez, Cecilia; Figueroa-Mujíca, Rómulo; Vizcardo-Galindo, Gustavo; Mercado, Andy; Macarlupú, José Luis; León-Velarde, Fabiola

2016-07-01

Excessive erythrocytosis (EE) is the main sign of Chronic Mountain Sickness (CMS), a highly prevalent syndrome in Andean highlanders. Low pulse O2 saturation (SpO2) during sleep and serum androgens have been suggested to contribute to EE in CMS patients. However, whether these factors have a significant impact on the erythropoietin (Epo) system leading to EE is still unclear. We have recently shown that morning soluble Epo receptor (sEpoR), an endogenous Epo antagonist, is decreased in CMS patients suggesting increased Epo availability (increased Epo/sEpoR). The present study aimed to characterize the nocturnal concentration profile of sEpoR and Epo and their relationship with SpO2, Hct, and serum testosterone in healthy highlanders (HH) and CMS patients. Epo and sEpoR concentrations were evaluated every 4 h (6 PM to 6 AM) and nighttime SpO2 was continuously monitored (10 PM to 6 AM) in 39 male participants (CMS, n = 23; HH, n = 16) aged 21-65 yr from Cerro de Pasco, Peru (4,340 m). CMS patients showed higher serum Epo concentrations throughout the night and lower sEpoR from 10 PM to 6 AM. Consequently, Epo/sEpoR was significantly higher in the CMS group at every time point. Mean sleep-time SpO2 was lower in CMS patients compared with HH, while the percentage of sleep time spent with SpO2 < 80% was higher. Multiple-regression analysis showed mean sleep-time SpO2 and Epo/sEpoR as significant predictors of hematocrit corrected for potential confounders (age, body mass index, and testosterone). Testosterone levels were associated neither with Hct nor with erythropoietic factors. In conclusion, our results show sustained erythropoietic stimulus driven by the Epo system in CMS patients, further enhanced by a continuous exposure to accentuated nocturnal hypoxemia. Copyright © 2016 the American Physiological Society.

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.

The effects of gentamicin and penicillin/streptomycin on the electrophysiology of human induced pluripotent stem cell-derived cardiomyocytes in manual patch clamp and multi-electrode array system.

PubMed

Hyun, Soo-Wang; Kim, Bo-Ram; Lin, Dan; Hyun, Sung-Ae; Yoon, Seong Shoon; Seo, Joung-Wook

Cell culture media usually contains antibiotics including gentamicin or penicillin/streptomycin (PS) to protect cells from bacterial contamination. However, little is known about the effects of antibiotics on action potential and field potential parameters in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The present study examined the effects of gentamicin (10, 25, and 50μg/ml) and PS (50, 100, and 200U/μg/ml) on electrophysiological activity in spontaneously beating hiPSC-CMs using manual patch clamp and multi-electrode array. We also measured mRNA expression of cardiac ion channels in hiPSC-CMs grown in media with or without gentamicin (25μg/ml) using reverse transcription-polymerase chain reaction. We recorded action potential and field potential of hiPSC-CMs grown in the presence or absence of gentamicin or PS. We also observed action potential parameters in hiPSC-CMs after short-term treatment with these antibiotics. Changes in action potential and field potential parameters were observed in hiPSC-CMs grown in media containing gentamicin or PS. Treatment with PS also affected action potential parameters in hiPSC-CMs. In addition, the mRNA expression of cardiac sodium and potassium ion channels was significantly attenuated in hiPSC-CMs grown in the presence of gentamicin (25μg/ml). The present findings suggested that gentamicin should not be used in the culture media of hiPSC-CMs used for the measurement of electrophysiological parameters. Our findings also suggest that 100U/100μg/ml of PS are the maximum appropriate concentrations of these antibiotics for recording action potential waveform, because they did not influence action potential parameters in these cells. Copyright © 2017. Published by Elsevier Inc.

Chinese version of the Constant-Murley questionnaire for shoulder pain and disability: a reliability and validation study.

PubMed

Yao, Min; Yang, Long; Cao, Zuo-Yuan; Cheng, Shao-Dan; Tian, Shuang-Lin; Sun, Yue-Li; Wang, Jing; Xu, Bao-Ping; Hu, Xiao-Chun; Wang, Yong-Jun; Zhang, Ying; Cui, Xue-Jun

2017-09-18

Shoulder pain is a common musculoskeletal disorder in Chinese population, which affects more than 1,3 billion individuals. To the best of our knowledge, there has been no available Chinese-language version of measurements of shoulder pain and disability so far. Moreover, the Constant-Murley score (CMS) questionnaire is a universally recognized patient-reported questionnaire for clinical practice and research. The present study was designed to evaluate a Chinese translational version of CMS and subsequently assess its reliability and validity. The Chinese translational version of CMS was formulated by means of forward-backward translation. Meanwhile, a final review was carried out by an expert committee, followed by conducting a test of the pre-final version. Therefore, the reliability and validity of the Chinese translational version of CMS could be assessed using the internal consistency, construct validity, factor analysis, reliability and floor and ceiling effects. Specifically, the reliability was assessed by testing the internal consistency (Cronbach's α) and test-retest reliability (intraclass coefficient correlation [ICC]), while the construct validity was evaluated via comparison between the Chinese translational version of CMS with visual analog scale (VAS) score and the 36-Item Short Form Health Survey (SF-36, Spearman correlation). The questionnaire was verified to be acceptable after distribution among 120 subjects with unilateral shoulder pain. Factor analysis had revealed a two-factor and 10-item solution. Moreover, the assessment results indicated that the Chinese translational version of CMS questionnaire harbored good internal consistency (Cronbach's α = 0.739) and test-retest reliability (ICC = 0.827). In addition, the Chinese translational version of CMS was moderately correlated with VAS score (r = 0.497) and SF-36 (r = 0.135). No obvious floor and ceiling effects were observed in the Chinese translational version of CMS questionnaire. Chinese translational version of CMS exhibited good reliability, which is relatively acceptable and is likely to be widely used in this population.

Plasma soluble erythropoietin receptor is decreased during sleep in Andean highlanders with Chronic Mountain Sickness

PubMed Central

Corante, Noemí; Anza-Ramírez, Cecilia; Figueroa-Mujíca, Rómulo; Vizcardo-Galindo, Gustavo; Mercado, Andy; Macarlupú, José Luis; León-Velarde, Fabiola

2016-01-01

Excessive erythrocytosis (EE) is the main sign of Chronic Mountain Sickness (CMS), a highly prevalent syndrome in Andean highlanders. Low pulse O2 saturation (SpO2) during sleep and serum androgens have been suggested to contribute to EE in CMS patients. However, whether these factors have a significant impact on the erythropoietin (Epo) system leading to EE is still unclear. We have recently shown that morning soluble Epo receptor (sEpoR), an endogenous Epo antagonist, is decreased in CMS patients suggesting increased Epo availability (increased Epo/sEpoR). The present study aimed to characterize the nocturnal concentration profile of sEpoR and Epo and their relationship with SpO2, Hct, and serum testosterone in healthy highlanders (HH) and CMS patients. Epo and sEpoR concentrations were evaluated every 4 h (6 PM to 6 AM) and nighttime SpO2 was continuously monitored (10 PM to 6 AM) in 39 male participants (CMS, n = 23; HH, n = 16) aged 21-65 yr from Cerro de Pasco, Peru (4,340 m). CMS patients showed higher serum Epo concentrations throughout the night and lower sEpoR from 10 PM to 6 AM. Consequently, Epo/sEpoR was significantly higher in the CMS group at every time point. Mean sleep-time SpO2 was lower in CMS patients compared with HH, while the percentage of sleep time spent with SpO2 < 80% was higher. Multiple-regression analysis showed mean sleep-time SpO2 and Epo/sEpoR as significant predictors of hematocrit corrected for potential confounders (age, body mass index, and testosterone). Testosterone levels were associated neither with Hct nor with erythropoietic factors. In conclusion, our results show sustained erythropoietic stimulus driven by the Epo system in CMS patients, further enhanced by a continuous exposure to accentuated nocturnal hypoxemia. PMID:27125843

Sex-dependent influence of chronic mild stress (CMS) on voluntary alcohol consumption; study of neurobiological consequences.

PubMed

Marco, Eva M; Ballesta, Javier Antonio; Irala, Carlos; Hernández, María-Donina; Serrano, María Elisa; Mela, Virginia; López-Gallardo, Meritxell; Viveros, María-Paz

2017-01-01

Alcohol use disorder and depression are highly comorbid, and both conditions exhibit important sexual dimorphisms. Here, we aimed to investigate voluntary alcohol consumption after 6weeks of chronic mild stress (CMS) in Wistar rats - employed as an animal model of depression. Male and female rats were investigated, and changes in several molecular markers were analysed in frontal cortex (FCx) and hippocampal formation (HF). CMS induced depressive-like responses in the forced swimming test - increased immobility time - in male and female animals, without affecting anhedonia (sucrose preference test) nor motor activity (holeboard); body weight gain and food intake were diminished only among CMS males. Voluntary alcohol consumption was evaluated in a two-bottle choice paradigm (ethanol 20% versus tap water) for 4 consecutive days; females exhibited a higher preference for alcohol compared to male animals. In particular, alcohol consumption was significantly higher among CMS females compared to CMS male animals. Remarkably, similar changes in both male and female animals exposed to CMS were observed regarding the expression levels of NCAM-140KDa (decrease), GFAP and CB1R expression (increase) within the FCx as well as for HF PSD-95 levels (increase). However, contrasting effects in males and females were reported in relation to synaptophysin (SYN) protein levels within the FCx, HF CB1R expression (a decrease among male animals but an increase in females); while the opposite pattern was observed for NCAM-140KDa protein levels in the HF. A decrease in CB2R expression was only observed in the HF of CMS-females. The present study suggests that male and female animals might be differentially affected by CMS regarding later voluntary alcohol consumption. In this initial approach, cortical SYN, and NCAM-140KDa, CB1R and CB2R expression within the HF have arisen as potential candidates to explain such sex differences in behaviour. However, the depression-alcoholism relationship still deserves further investigation. Copyright © 2016. Published by Elsevier Inc.

Development of BEM for ceramic composites

NASA Technical Reports Server (NTRS)

Henry, D. P.; Banerjee, P. K.; Dargush, G. F.; Hopkins, D. A.; Goldberg, R. K.

1993-01-01

BEST-CMS (boundary element solution technology - composite modeling system) is an advanced engineering system for the micro-analysis of fiber composite structures. BEST-CMS is based upon the boundary element program BEST3D which was developed for NASA by Pratt and Whitney Aircraft and the State University of New York at Buffalo under contract NAS3-23697. BEST-CMS presently has the capabilities for elastostatic analysis, steady-state and transient heat transfer analysis, steady-state and transient concurrent thermoelastic analysis, and elastoplastic and creep analysis. The fibers are assumed to be perfectly bonded to the composite matrix, or in the case of static or steady-state analysis, the fibers may be assumed to have spring connections, thermal resistance, and/or frictional sliding between the fibers and the composite matrix. The primary objective of this user's manual is to provide an overview of all BEST-CMS capabilities, along with detailed descriptions of the input data requirements. In the next chapter, a brief review of the theoretical background is presented for each analysis category. Then, chapter three discusses the key aspects of the numerical implementation, while chapter four provides a tutorial for the beginning BEST-CMS user. The heart of the manual, however, is in chapter five, where a complete description of all data input items is provided. Within this chapter, the individual entries are grouped on a functional basis for a more coherent presentation. Chapter six includes sample problems and should be of considerable assistance to the novice. Chapter seven includes capsules of a number of fiber-composite analysis problems that have been solved using BEST-CMS. This chapter is primarily descriptive in nature and is intended merely to illustrate the level of analysis that is possible within the present BEST-CMS system. Chapter eight contains a detail description of the BEST-CMS Neutral File which is helpful in writing an interface between BEST-CMS and any graphic post-processor program. Finally, all pertinent references are listed in chapter nine.

The profitability of automatic milking on Dutch dairy farms.

PubMed

Bijl, R; Kooistra, S R; Hogeveen, H

2007-01-01

Several studies have reported on the profitability of automatic milking based on different simulation models, but a data-based study using actual farm data has been lacking. The objective of this study was to analyze the profitability of dairy farms having an automatic milking system (AMS) compared with farms using a conventional milking system (CMS) based on real accounting data. In total, 62 farms (31 using an AMS and 31 using a CMS) were analyzed for the year 2003 in a case control study. Differences between the years 2002 and 2003 also were analyzed by comparing a subgroup of 16 farms with an AMS and 16 farms with a CMS. Matching was based on the time of investment in a milking system (same year), the total milk production per year, and intensity of land use (kg/ha). Results from 2003 showed that the farms with an AMS used, on average, 29% less labor than farms with a CMS. In contrast, farms using a CMS grew faster (37,132 kg of milk quota and 5 dairy cows) than farms with an AMS (-3,756 kg milk quota and 0.5 dairy cows) between 2002 and 2003. Dairy farmers with a CMS had larger (euro7,899) revenues than those with an AMS. However, no difference in the margin on dairy production was detected, partly because of numerically greater (euro6,822) variable costs on CMS farms. Dairy farms were compared financially based on the amount of money that was available for rent, depreciation, interest, labor, and profit (RDILP). The CMS farms had more money (euro15,566) available for RDILP than the AMS farms. This difference was caused by larger fixed costs (excluding labor) for the AMS farms, larger contractor costs (euro6,422), and larger costs for gas, water, and electricity (euro1,549). Differences in costs for contractors and for gas, water, and electricity were statistically significant. When expressed per full-time employee, AMS farms had greater revenues, margins, and gross margins per full-time employee than did CMS farms. This resulted in a substantially greater (but not statistically significant) RDILP per full-time employee (euro12,953) for AMS farms compared with CMS farms. Depreciation and interest costs for automatic milking were not available but were calculated based on several assumptions. Assuming larger purchase costs and a shorter depreciation time for AMS than for CMS, costs for depreciation and interest were larger for AMS farms than for CMS farms. Larger fixed costs should be compensated for by the amount of labor that has become available after introducing the milking robot. Therefore, farm managers should decide whether the extra time acquired by automatic milking balances against the extra costs associated with an AMS.

Hyaluronic acid oligosaccharide modified redox-responsive mesoporous silica nanoparticles for targeted drug delivery.

PubMed

Zhao, Qinfu; Geng, Hongjian; Wang, Ying; Gao, Yikun; Huang, Jiahao; Wang, Yan; Zhang, Jinghai; Wang, Siling

2014-11-26

A redox-responsive delivery system based on colloidal mesoporous silica (CMS) has been developed, in which 6-mercaptopurine (6-MP) was conjugated to vehicles by cleavable disulfide bonds. The oligosaccharide of hyaluronic acid (oHA) was modified on the surface of CMS by disulfide bonds as a targeting ligand and was able to increase the stability and biocompatibility of CMS under physiological conditions. In vitro release studies indicated that the cumulative release of 6-MP was less than 3% in the absence of glutathione (GSH), and reached nearly 80% within 2 h in the presence of 3 mM GSH. Confocal microscopy and fluorescence-activated cell sorter (FACS) methods were used to evaluate the cellular uptake performance of fluorescein isothiocyanate (FITC) labeled CMS, with and without oHA modification. The CMS-SS-oHA exhibited a higher cellular uptake performance via CD44 receptor-mediated endocytosis in HCT-116 (CD44 receptor-positive) cells than in NIH-3T3 (CD44 receptor-negative) cells. 6-MP loaded CMS-SS-oHA exhibited greater cytotoxicity against HCT-116 cells than NIH-3T3 cells due to the enhanced cell uptake behavior of CMS-SS-oHA. This study provides a novel strategy to covalently link bioactive drug and targeting ligand to the interiors and exteriors of mesoporous silica to construct a stimulus-responsive targeted drug delivery system.

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.

Modeling and study of the mechanism of dilated cardiomyopathy using induced pluripotent stem cells derived from individuals with Duchenne muscular dystrophy.

PubMed

Lin, Bo; Li, Yang; Han, Lu; Kaplan, Aaron D; Ao, Ying; Kalra, Spandan; Bett, Glenna C L; Rasmusson, Randall L; Denning, Chris; Yang, Lei

2015-05-01

Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene (DMD), and is characterized by progressive weakness in skeletal and cardiac muscles. Currently, dilated cardiomyopathy due to cardiac muscle loss is one of the major causes of lethality in late-stage DMD patients. To study the molecular mechanisms underlying dilated cardiomyopathy in DMD heart, we generated cardiomyocytes (CMs) from DMD and healthy control induced pluripotent stem cells (iPSCs). DMD iPSC-derived CMs (iPSC-CMs) displayed dystrophin deficiency, as well as the elevated levels of resting Ca(2+), mitochondrial damage and cell apoptosis. Additionally, we found an activated mitochondria-mediated signaling network underlying the enhanced apoptosis in DMD iPSC-CMs. Furthermore, when we treated DMD iPSC-CMs with the membrane sealant Poloxamer 188, it significantly decreased the resting cytosolic Ca(2+) level, repressed caspase-3 (CASP3) activation and consequently suppressed apoptosis in DMD iPSC-CMs. Taken together, using DMD patient-derived iPSC-CMs, we established an in vitro model that manifests the major phenotypes of dilated cardiomyopathy in DMD patients, and uncovered a potential new disease mechanism. Our model could be used for the mechanistic study of human muscular dystrophy, as well as future preclinical testing of novel therapeutic compounds for dilated cardiomyopathy in DMD patients. © 2015. Published by The Company of Biologists Ltd.

The Brazilian version of the Constant-Murley Score (CMS-BR): convergent and construct validity, internal consistency, and unidimensionality.

PubMed

Barreto, Rodrigo Py Gonçalves; Barbosa, Marcus Levi Lopes; Balbinotti, Marcos Alencar Abaide; Mothes, Fernando Carlos; da Rosa, Luís Henrique Telles; Silva, Marcelo Faria

2016-01-01

To translate and culturally adapt the CMS and assess the validity of the Brazilian version (CMS-BR). The translation was carried out according to the back-translation method by four independent translators. The produced versions were synthesized through extensive analysis and by consensus of an expert committee, reaching a final version used for the cultural adaptation. A field test was conducted with 30 subjects in order to obtain semantic considerations. For the psychometric analyzes, the sample was increased to 110 participants who answered two instruments: CMS-BR and the Disabilities of the Arm, shoulder and Hand (DASH). The CMS-BR and DASH score range from 0 to 100 points. For the first, higher points reflect better function and for the latter, the inverse is true. The validity was verified by Pearson's correlation test, the unidimensionality by factorial analysis, and the internal consistency by Cronbach's alpha. The explained variance was 60.28% with factor loadings ranging from 0.60 to 0.91. The CMS-BR exhibited strong negative correlation with the DASH score (-0.82, p  < 0.05), Cronbach's alpha 0.85, and its total score was strongly correlated with the patient's range of motion (0.93, p  < 0.001). The CMS was satisfactorily adapted for Brazilian Portuguese and demonstrated evidence of validity that allows its use in this population.

Draft genome of Kocuria polaris CMS 76or(T) isolated from cyanobacterial mats, McMurdo Dry Valley, Antarctica: an insight into CspA family of proteins from Kocuria polaris CMS 76or(T).

PubMed

Gundlapally, Sathyanarayana Reddy; Ara, Srinivas; Sisinthy, Shivaji

2015-10-01

Kocuria polaris strain CMS 76or(T) is a gram-positive, orange-pigmented bacterium isolated from a cyanobacterial mat sample from a pond located in McMurdo Dry Valley, Antarctica. It is psychrotolerant, orange pigmented, hydrolyses starch and Tween 80 and reduces nitrate. We report the 3.78-Mb genome of K. polaris strain CMS 76or(T), containing 3416 coding sequences, including one each for 5S rRNA, 23S rRNA, 16S rRNA and 47 tRNA genes, and the G+C content of DNA is 72.8%. An investigation of Csp family of proteins from K. polaris strain CMS 76or(T) indicated that it contains three different proteins of CspA (peg.319, peg.2255 and 2832) and the length varied from 67 to 69 amino acids. The three different proteins contain all the signature amino acids and two RNA binding regions that are characteristic of CspA proteins. Further, the CspA from K. polaris strain CMS 76or(T) was different from CspA of four other species of the genus Kocuria, Cryobacterium roopkundense and E. coli indirectly suggesting the role of CspA of K. polaris strain CMS 76or(T) in psychrotolerant growth of the bacterium.

42 CFR 488.68 - State Agency responsibilities for OASIS collection and data base requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... operating the OASIS system: (a) Establish and maintain an OASIS database. The State agency or other entity designated by CMS must— (1) Use a standard system developed or approved by CMS to collect, store, and analyze..., system back-up, and monitoring the status of the database; and (3) Obtain CMS approval before modifying...

42 CFR 495.204 - Incentive payments to qualifying MA organizations for MA-EPs and MA-affiliated eligible hospitals.

Code of Federal Regulations, 2012 CFR

2012-10-01

.... (iii) Methodological proposals must be submitted to CMS by June of the payment year and must be... the payment year. (4) CMS requires the qualifying MA organization to develop a methodological proposal... MA organization in the payment year. The methodological proposal— (i) Must be approved by CMS; and...

42 CFR 488.431 - Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF-only facilities. 488... imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF...

42 CFR 488.431 - Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF-only facilities. 488... imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF...

42 CFR 488.431 - Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF-only facilities. 488... imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF...

42 CFR 488.431 - Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS...

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF-only facilities. 488... imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF...

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

Code of Federal Regulations, 2012 CFR

2012-10-01

... level of financial and other impacts on affected individuals. (3) Other factors as justice may require. ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Factors CMS uses to determine the amount of... With Respect to Issuers and Non-Federal Governmental Plans-Civil Money Penalties § 150.317 Factors CMS...

77 FR 3477 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-24

... collection for the proper performance of the agency's functions; (2) the accuracy of the estimated burden; (3... submitted to CMS through the 372 web-based form. The report is used by CMS to compare actual data in the... provided is compared to that in the Medicaid Statistical Information System (CMS-R-284, OCN 0938-0345...

Better Off with or without Your CMS? 5 Kinds of Assessment That Can Really Help.

ERIC Educational Resources Information Center

Ehrmann, Stephen C.; Gilbert, Steven W.

2003-01-01

Presents five areas to consider to help establish the value and improve the effectiveness of a course management system (CMS). Highlights include faculty use to improve teaching effectiveness; changes in support strategies to improve the value of a CMS; increasing enrollment or retention; controlling costs; and identifying barriers to desired…

75 FR 80058 - Notice of Hearing: Reconsideration of Disapproval of California State Plan Amendments (SPAs) 08...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-21

...; and 08-019 AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Notice of hearing. SUMMARY: This notice announces an administrative hearing to be held on February 10, 2011, at the CMS San Francisco Regional Office, 90 7th Street, 5-300 (5W), San Francisco, California 94103 to reconsider CMS...

Coastal Modeling System

DTIC Science & Technology

2015-11-04

Coastal Inlets Research Program Coastal Modeling System The work unit develops the Coastal Modeling System ( CMS ) and conducts basic research to...further understanding of sediment transport under mixed oceanic and atmospheric forcing. The CMS is a suite of coupled two-dimensional numerical...models for simulations of waves, hydrodynamics, salinity and sediment transport, and morphology change. The CMS was identified by the USACE Hydraulics

Tool-Use in a Content Management System: A Matter of Timing?

ERIC Educational Resources Information Center

Lust, Griet; Vandewaetere, Mieke; Elen, Jan; Clarebout, Geraldine

2014-01-01

Given the rising popularity of content management systems (CMSs) in higher education, we investigated how students use the available CMS tools, as well as whether the moment of using a CMS tool affects students' learning. This temporal dimension has been neglected in current research on CMS use. More insight into students' tool-use is…

A Planning and Assessment Model for Developing Effective CMS Support

ERIC Educational Resources Information Center

Johnson, Douglas F.

2004-01-01

At the University of Florida, in Spring 2003, more than 32,000 individuals enrolled in courses using the centrally-supported Course Management System (CMS). Because less than 1 full time equivalent (FTE) was allocated to support the CMS, this created problems for both users and support providers. In the face of rapid growth, support resources for…

Cardiometabolic Syndrome in People With Spinal Cord Injury/Disease: Guideline-Derived and Nonguideline Risk Components in a Pooled Sample.

PubMed

Nash, Mark S; Tractenberg, Rochelle E; Mendez, Armando J; David, Maya; Ljungberg, Inger H; Tinsley, Emily A; Burns-Drecq, Patricia A; Betancourt, Luisa F; Groah, Suzanne L

2016-10-01

To assess cardiometabolic syndrome (CMS) risk definitions in spinal cord injury/disease (SCI/D). Cross-sectional analysis of a pooled sample. Two SCI/D academic medical and rehabilitation centers. Baseline data from subjects in 7 clinical studies were pooled; not all variables were collected in all studies; therefore, participant numbers varied from 119 to 389. The pooled sample included men (79%) and women (21%) with SCI/D >1 year at spinal cord levels spanning C3-T2 (American Spinal Injury Association Impairment Scale [AIS] grades A-D). Not applicable. We computed the prevalence of CMS using the American Heart Association/National Heart, Lung, and Blood Institute guideline (CMS diagnosis as sum of risks ≥3 method) for the following risk components: overweight/obesity, insulin resistance, hypertension, and dyslipidemia. We compared this prevalence with the risk calculated from 2 routinely used nonguideline CMS risk assessments: (1) key cut scores identifying insulin resistance derived from the homeostatic model 2 (HOMA2) method or quantitative insulin sensitivity check index (QUICKI), and (2) a cardioendocrine risk ratio based on an inflammation (C-reactive protein [CRP])-adjusted total cholesterol/high-density lipoprotein cholesterol ratio. After adjustment for multiple comparisons, injury level and AIS grade were unrelated to CMS or risk factors. Of the participants, 13% and 32.1% had CMS when using the sum of risks or HOMA2/QUICKI model, respectively. Overweight/obesity and (pre)hypertension were highly prevalent (83% and 62.1%, respectively), with risk for overweight/obesity being significantly associated with CMS diagnosis (sum of risks, χ(2)=10.105; adjusted P=.008). Insulin resistance was significantly associated with CMS when using the HOMA2/QUICKI model (χ(2)2=21.23, adjusted P<.001). Of the subjects, 76.4% were at moderate to high risk from elevated CRP, which was significantly associated with CMS determination (both methods; sum of risks, χ(2)2=10.198; adjusted P=.048 and HOMA2/QUICKI, χ(2)2=10.532; adjusted P=.04). As expected, guideline-derived CMS risk factors were prevalent in individuals with SCI/D. Overweight/obesity, hypertension, and elevated CRP were common in SCI/D and, because they may compound risks associated with CMS, should be considered population-specific risk determinants. Heightened surveillance for risk, and adoption of healthy living recommendations specifically directed toward weight reduction, hypertension management, and inflammation control, should be incorporated as a priority for disease prevention and management. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Eff ect of a single asenapine treatment on Fos expression in the brain catecholamine-synthesizing neurons: impact of a chronic mild stress preconditioning.

PubMed

Osacka, J; Horvathova, L; Majercikova, Z; Kiss, Alexander

2017-04-25

Fos protein expression in catecholamine-synthesizing neurons of the substantia nigra (SN) pars compacta (SNC, A8), pars reticulata (SNR, A9), and pars lateralis (SNL), the ventral tegmental area (VTA, A10), the locus coeruleus (LC, A6) and subcoeruleus (sLC), the ventrolateral pons (PON-A5), the nucleus of the solitary tract (NTS-A2), the area postrema (AP), and the ventrolateral medulla (VLM-A1) was quantitatively evaluated aft er a single administration of asenapine (ASE) (designated for schizophrenia treatment) in male Wistar rats preconditioned with a chronic unpredictable variable mild stress (CMS) for 21 days. Th e aim of the present study was to reveal whether a single ASE treatment may 1) activate Fos expression in the brain areas selected; 2) activate tyrosine hydroxylase (TH)-synthesizing cells displaying Fos presence; and 3) be modulated by CMS preconditioning. Control (CON), ASE, CMS, and CMS+ASE groups were used. CMS included restraint, social isolation, crowding, swimming, and cold. Th e ASE and CMS+ASE groups received a single dose of ASE (0.3 mg/kg, s.c.) and CON and CMS saline (300 μl/rat, s.c.). The animals were sacrificed 90 min aft er the treatments. Fos protein and TH-labeled immunoreactive perikarya were analyzed on double labeled histological sections and enumerated on captured pictures using combined light and fluorescence microscope illumination. Saline or CMS alone did not promote Fos expression in any of the structures investigated. ASE alone or in combination with CMS elicited Fos expression in two parts of the SN (SNC, SNR) and the VTA. Aside from some cells in the central gray tegmental nuclei adjacent to LC, where a small number of Fos profiles occurred, none or negligible Fos occurrence was detected in the other structures investigated including the LC and sLC, PON-A5, NTS-A2, AP, and VLM-A1. CMS preconditioning did not infl uence the level of Fos induction in the SN and VTA elicited by ASE administration. Similarly, the ratio between the amount of free Fos and Fos colocalized with TH was not aff ected by stress preconditioning in the SNC, SNR, and the VTA. Th e present study provides an anatomical/functional knowledge about the nature of the acute ASE treatment on the catecholamine-synthesizing neurons activity in certain brain structures and their missing interplay with the CMS preconditioning.

Single cell qPCR reveals that additional HAND2 and microRNA-1 facilitate the early reprogramming progress of seven-factor-induced human myocytes

PubMed Central

Bektik, Emre; Dennis, Adrienne; Prasanna, Prateek; Madabhushi, Anant

2017-01-01

The direct reprogramming of cardiac fibroblasts into induced cardiomyocyte (CM)-like cells (iCMs) holds great promise in restoring heart function. We previously found that human fibroblasts could be reprogrammed toward CM-like cells by 7 reprogramming factors; however, iCM reprogramming in human fibroblasts is both more difficult and more time-intensive than that in mouse cells. In this study, we investigated if additional reprogramming factors could quantitatively and/or qualitatively improve 7-factor-mediated human iCM reprogramming by single-cell quantitative PCR. We first validated 46 pairs of TaqMan® primers/probes that had sufficient efficiency and sensitivity to detect the significant difference of gene expression between individual H9 human embryonic stem cell (ESC)-differentiated CMs (H9CMs) and human fibroblasts. The expression profile of these 46 genes revealed an improved reprogramming in 12-week iCMs compared to 4-week iCMs reprogrammed by 7 factors, indicating a prolonged stochastic phase during human iCM reprogramming. Although none of additional one reprogramming factor yielded a greater number of iCMs, our single-cell qPCR revealed that additional HAND2 or microRNA-1 could facilitate the silencing of fibroblast genes and yield a better degree of reprogramming in more reprogrammed iCMs. Noticeably, the more HAND2 expressed, the higher-level were cardiac genes activated in 7Fs+HAND2-reprogrammed iCMs. In conclusion, HAND2 and microRNA-1 could help 7 factors to facilitate the early progress of iCM-reprogramming from human fibroblasts. Our study provides valuable information to further optimize a method of direct iCM-reprogramming in human cells. PMID:28796841

Single cell qPCR reveals that additional HAND2 and microRNA-1 facilitate the early reprogramming progress of seven-factor-induced human myocytes.

PubMed

Bektik, Emre; Dennis, Adrienne; Prasanna, Prateek; Madabhushi, Anant; Fu, Ji-Dong

2017-01-01

The direct reprogramming of cardiac fibroblasts into induced cardiomyocyte (CM)-like cells (iCMs) holds great promise in restoring heart function. We previously found that human fibroblasts could be reprogrammed toward CM-like cells by 7 reprogramming factors; however, iCM reprogramming in human fibroblasts is both more difficult and more time-intensive than that in mouse cells. In this study, we investigated if additional reprogramming factors could quantitatively and/or qualitatively improve 7-factor-mediated human iCM reprogramming by single-cell quantitative PCR. We first validated 46 pairs of TaqMan® primers/probes that had sufficient efficiency and sensitivity to detect the significant difference of gene expression between individual H9 human embryonic stem cell (ESC)-differentiated CMs (H9CMs) and human fibroblasts. The expression profile of these 46 genes revealed an improved reprogramming in 12-week iCMs compared to 4-week iCMs reprogrammed by 7 factors, indicating a prolonged stochastic phase during human iCM reprogramming. Although none of additional one reprogramming factor yielded a greater number of iCMs, our single-cell qPCR revealed that additional HAND2 or microRNA-1 could facilitate the silencing of fibroblast genes and yield a better degree of reprogramming in more reprogrammed iCMs. Noticeably, the more HAND2 expressed, the higher-level were cardiac genes activated in 7Fs+HAND2-reprogrammed iCMs. In conclusion, HAND2 and microRNA-1 could help 7 factors to facilitate the early progress of iCM-reprogramming from human fibroblasts. Our study provides valuable information to further optimize a method of direct iCM-reprogramming in human cells.

Human induced pluripotent stem cell-derived cardiomyocytes as an in vitro model for coxsackievirus B3-induced myocarditis and antiviral drug screening platform.

PubMed

Sharma, Arun; Marceau, Caleb; Hamaguchi, Ryoko; Burridge, Paul W; Rajarajan, Kuppusamy; Churko, Jared M; Wu, Haodi; Sallam, Karim I; Matsa, Elena; Sturzu, Anthony C; Che, Yonglu; Ebert, Antje; Diecke, Sebastian; Liang, Ping; Red-Horse, Kristy; Carette, Jan E; Wu, Sean M; Wu, Joseph C

2014-08-29

Viral myocarditis is a life-threatening illness that may lead to heart failure or cardiac arrhythmias. A major causative agent for viral myocarditis is the B3 strain of coxsackievirus, a positive-sense RNA enterovirus. However, human cardiac tissues are difficult to procure in sufficient enough quantities for studying the mechanisms of cardiac-specific viral infection. This study examined whether human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could be used to model the pathogenic processes of coxsackievirus-induced viral myocarditis and to screen antiviral therapeutics for efficacy. hiPSC-CMs were infected with a luciferase-expressing coxsackievirus B3 strain (CVB3-Luc). Brightfield microscopy, immunofluorescence, and calcium imaging were used to characterize virally infected hiPSC-CMs for alterations in cellular morphology and calcium handling. Viral proliferation in hiPSC-CMs was quantified using bioluminescence imaging. Antiviral compounds including interferonβ1, ribavirin, pyrrolidine dithiocarbamate, and fluoxetine were tested for their capacity to abrogate CVB3-Luc proliferation in hiPSC-CMs in vitro. The ability of these compounds to reduce CVB3-Luc proliferation in hiPSC-CMs was consistent with reported drug effects in previous studies. Mechanistic analyses via gene expression profiling of hiPSC-CMs infected with CVB3-Luc revealed an activation of viral RNA and protein clearance pathways after interferonβ1 treatment. This study demonstrates that hiPSC-CMs express the coxsackievirus and adenovirus receptor, are susceptible to coxsackievirus infection, and can be used to predict antiviral drug efficacy. Our results suggest that the hiPSC-CM/CVB3-Luc assay is a sensitive platform that can screen novel antiviral therapeutics for their effectiveness in a high-throughput fashion. © 2014 American Heart Association, Inc.

Form CMS-2728 data versus erythropoietin claims data: implications for quality of care studies.

PubMed

Beaubrun, Anne C; Kanda, Eiichiro; Bond, T Christopher; McClellan, William M

2013-01-01

Medical Evidence Report Form CMS-2728 data is frequently used to study US dialysis patients, but the validity of these data have been called into question. We compared predialysis erythropoietin use as recorded on Form CMS-2728 with claims data as part of an assessment of quality of care among hemodialysis patients. Medicare claims were linked to Form CMS-2728 data for 18,870 patients. Dialysis patients, 67 years old or older, who started dialysis from 1 June 2005 to 31 May 2007 were eligible. Logistic and multivariate regressions were used to compare the use of either Form CMS-2728 or the corresponding claims data to predict mortality and the probability of meeting target hemoglobin levels. The sensitivity, specificity, and kappa coefficient for the predialysis erythropoietin indicator were 58.0%, 78.4%, and 0.36, respectively. Patients with a predialysis erythropoietin claim were less likely to die compared with patients without a claim (odds ratio = 0.80 and 95% confidence interval = 0.74-0.87), but there was no relationship observed between predialysis care and death using only Form CMS-2728 predictors. At the facility level, a predialysis erythropoietin claim was associated with a 0.085 increase in the rate of meeting target hemoglobin levels compared with patients without a claim (p = 0.041), but no statistically significant relationship was observed when using the Form CMS-2728 indicators. The agreement between Form CMS-2728 and claims data is poor and discordant results are observed when comparing the use of these data sources to predict health outcomes. Facilities with higher agreement between the two data sources may provide greater quality of care.

Tailored dendritic core-multishell nanocarriers for efficient dermal drug delivery: A systematic top-down approach from synthesis to preclinical testing.

PubMed

Hönzke, Stefan; Gerecke, Christian; Elpelt, Anja; Zhang, Nan; Unbehauen, Michael; Kral, Vivian; Fleige, Emanuel; Paulus, Florian; Haag, Rainer; Schäfer-Korting, Monika; Kleuser, Burkhard; Hedtrich, Sarah

2016-11-28

Drug loaded dendritic core-multishell (CMS) nanocarriers are of especial interest for the treatment of skin diseases, owing to their striking dermal delivery efficiencies following topical applications. CMS nanocarriers are composed of a polyglycerol core, connected by amide-bonds to an inner alkyl shell and an outer methoxy poly(ethylene glycol) shell. Since topically applied nanocarriers are subjected to biodegradation, the application of conventional amide-based CMS nanocarriers (10-A-18-350) has been limited by the potential production of toxic polyglycerol amines. To circumvent this issue, three tailored ester-based CMS nanocarriers (10-E-12-350, 10-E-15-350, 10-E-18-350) of varying inner alkyl chain length were synthesized and comprehensively characterized in terms of particle size, drug loading, biodegradation and dermal drug delivery efficiency. Dexamethasone (DXM), a potent drug widely used for the treatment of inflammatory skin diseases, was chosen as a therapeutically relevant test compound for the present study. Ester- and amide-based CMS nanocarriers delivered DXM more efficiently into human skin than a commercially available DXM cream. Subsequent in vitro and in vivo toxicity studies identified CMS (10-E-15-350) as the most biocompatible carrier system. The anti-inflammatory potency of DXM-loaded CMS (10-E-15-350) nanocarriers was assessed in TNFα supplemented skin models, where a significant reduction of the pro-inflammatory cytokine IL-8 was seen, with markedly greater efficacy than commercial DXM cream. In summary, we report the rational design and characterization of tailored, biodegradable, ester-based CMS nanocarriers, and their subsequent stepwise screening for biocompatibility, dermal delivery efficiency and therapeutic efficacy in a top-down approach yielding the best carrier system for topical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparing 2 methods of assessing 30-day readmissions: what is the impact on hospital profiling in the veterans health administration?

PubMed

Mull, Hillary J; Chen, Qi; O'Brien, William J; Shwartz, Michael; Borzecki, Ann M; Hanchate, Amresh; Rosen, Amy K

2013-07-01

The Centers for Medicare and Medicaid Services' (CMS) all-cause readmission measure and the 3M Health Information System Division Potentially Preventable Readmissions (PPR) measure are both used for public reporting. These 2 methods have not been directly compared in terms of how they identify high-performing and low-performing hospitals. To examine how consistently the CMS and PPR methods identify performance outliers, and explore how the PPR preventability component impacts hospital readmission rates, public reporting on CMS' Hospital Compare website, and pay-for-performance under CMS' Hospital Readmission Reduction Program for 3 conditions (acute myocardial infarction, heart failure, and pneumonia). We applied the CMS all-cause model and the PPR software to VA administrative data to calculate 30-day observed FY08-10 VA hospital readmission rates and hospital profiles. We then tested the effect of preventability on hospital readmission rates and outlier identification for reporting and pay-for-performance by replacing the dependent variable in the CMS all-cause model (Yes/No readmission) with the dichotomous PPR outcome (Yes/No preventable readmission). The CMS and PPR methods had moderate correlations in readmission rates for each condition. After controlling for all methodological differences but preventability, correlations increased to >90%. The assessment of preventability yielded different outlier results for public reporting in 7% of hospitals; for 30% of hospitals there would be an impact on Hospital Readmission Reduction Program reimbursement rates. Despite uncertainty over which readmission measure is superior in evaluating hospital performance, we confirmed that there are differences in CMS-generated and PPR-generated hospital profiles for reporting and pay-for-performance, because of methodological differences and the PPR's preventability component.

Dual-RiverSonde measurements of two-dimensional river flow patterns

USGS Publications Warehouse

Teague, C.C.; Barrick, D.E.; Lilleboe, P.M.; Cheng, R.T.; Stumpner, P.; Burau, J.R.

2008-01-01

Two-dimensional river flow patterns have been measured using a pair of RiverSondes in two experiments in the Sacramento-San Joaquin River Delta system of central California during April and October 2007. An experiment was conducted at Walnut Grove, California in order to explore the use of dual RiverSondes to measure flow patterns at a location which is important in the study of juvenile fish migration. The data available during the first experiment were limited by low wind, so a second experiment was conducted at Threemile Slough where wind conditions and surface turbulence historically have resulted in abundant data. Both experiments included ADCP near-surface velocity measurements from either manned or unmanned boats. Both experiments showed good comparisons between the RiverSonde and ADCP measurements. The flow conditions at both locations are dominated by tidal effects, with partial flow reversal at Walnut Grove and complete flow reversal at Threemile Slough. Both systems showed complex flow patterns during the flow reversals. Quantitative comparisons between the RiverSondes and an ADCP on a manned boat at Walnut Grove showed mean differences of 4.5 cm/s in the u (eastward) and 7.6 cm/s in the v (northward) components, and RMS differences of 14.7 cm/s in the u component and 21.0 cm/s in the v component. Quantitative comparisons between the RiverSondes and ADCPs on autonomous survey vessels at Threemile Slough showed mean differences of 0.007 cm/s in the u component and 0.5 cm/s in the v component, and RMS differences of 7.9 cm/s in the u component and 13.5 cm/s in the v component after obvious outliers were removed. ?? 2008 IEEE.

Turkish version of the modified Constant-Murley score and standardized test protocol: reliability and validity.

PubMed

Çelik, Derya

2016-01-01

The Constant-Murley score (CMS) is widely used to evaluate disabilities associated with shoulder injuries, but it has been criticized for relying on imprecise terminology and a lack of standardized methodology. A modified guideline, therefore, was published in 2008 with several recommendations. This new version has not yet been translated or culturally adapted for Turkish-speaking populations. The purpose of this study was to translate and cross-culturally adapt the modified CMS and its test protocol, as well as define and measure its reliability and validity. The modified CMS was translated into Turkish, consistent with published methodological guidelines. The measurement properties of the Turkish version of the modified CMS were tested in 30 patients (12 males, 18 females; mean age: 59.5±13.5 years) with a variety of shoulder pathologies. Intraclass correlation coefficients (ICC) were used to estimate test-retest reliability. Construct validity was analyzed with the Turkish version of the American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form and Short-Form Health Survey (SF-12). No difficulties were found in the translation process. The Turkish version of the modified CMS showed excellent test-retest reliability (ICC=0.86). The correlation coefficients between the Turkish version of the modified CMS and the ASES, SF-12-physical component score, and SF-12 mental component scores were found to be 0.48, 0.35, and 0.05, respectively. No floor or ceiling effects were found. The translation and cultural adaptation of the modified CMS and its standardized test protocol into Turkish were successful. The Turkish version of the modified CMS has sufficient reliability and validity to measure a variety of shoulder disorders for Turkish-speaking individuals.

Development of a novel allele-specific Rfo marker and creation of Ogura CMS fertility-restored interspecific hybrids in Brassica oleracea.

PubMed

Yu, Hai-Long; Fang, Zhi-Yuan; Liu, Yu-Mei; Yang, Li-Mei; Zhuang, Mu; Lv, Hong-Hao; Li, Zhan-Sheng; Han, Feng-Qing; Liu, Xiao-Ping; Zhang, Yang-Yong

2016-08-01

A novel allele-specific Rfo marker was developed and proved to be effective for MAS of Rfo gene in B. oleracea background and six Ogu-CMS fertility-restored interspecific hybrids were created for the first time. Ogura cytoplasmic male sterility (Ogu-CMS) has been extensively used for Brassica oleracea hybrid production. However, because of maternal inheritance, all the hybrids produced by CMS lines are male sterile and cannot be self-pollinated, which prohibits germplasm maintenance and innovation. This problem can be overcome by using the Ogu-CMS restorer line, but restorer material is absent in B. oleracea crops. Here, Rfo, a fertility-restored gene of Ogu-CMS, was transferred from rapeseed restorer lines into a Chinese kale Ogu-CMS line using interspecific hybridization combined with embryo rescue. Nine interspecific, triploid plant progenies were identified at morphological and ploidy level, with phenotypes intermediate between those of rapeseed and Chinese kale. Because the Rfo marker (Hu et al., Mol Breeding 22:663-674, 2008) cannot distinguish the Rfo and its homologies under a B. oleracea background, a novel allele-specific Rfo marker was developed based on the BLAST analysis of highly homologous Rfo sequences in B. oleracea. Screening using the novel Rfo marker found that six interspecific hybrids carrying Rfo were also fertile, although fertility varied during different flowering periods. Furthermore, BC1 offsprings with the Rfo gene were selected with the allele-specific Rfo marker and showed restored fertility. These results indicated that the novel allele-specific marker could be used for the MAS of Rfo gene in B. oleracea, and this study lays the foundation for the development of Ogu-CMS restorer material in cabbage and its related other subspecies.

Congenital myasthenic syndrome with episodic apnoea: clinical, neurophysiological and genetic features in the long-term follow-up of 19 patients.

PubMed

McMacken, Grace; Whittaker, Roger G; Evangelista, Teresinha; Abicht, Angela; Dusl, Marina; Lochmüller, Hanns

2018-01-01

Congenital myasthenic syndrome with episodic apnoea (CMS-EA) is a rare but potentially treatable cause of apparent life-threatening events in infancy. The underlying mechanisms for sudden and recurrent episodes of respiratory arrest in these patients are unclear. Whilst CMS-EA is most commonly caused by mutations in CHAT, the list of associated genotypes is expanding. We reviewed clinical information from 19 patients with CMS-EA, including patients with mutations in CHAT, SLC5A7 and RAPSN, and patients lacking a genetic diagnosis. Lack of genetic diagnosis was more common in CMS-EA than in CMS without EA (56% n = 18, compared to 7% n = 97). Most patients manifested intermittent apnoea in the first 4 months of life (74%, n = 14). A degree of clinical improvement with medication was observed in most patients (74%, n = 14), but the majority of cases also showed a tendency towards complete remission of apnoeic events with age (mean age of resolution 2 years 5 months). Signs of impaired neuromuscular transmission were detected on neurophysiology studies in 79% (n = 15) of cases, but in six cases, this was only apparent following specific neurophysiological testing protocols (prolonged high-frequency stimulation). A relatively large proportion of CMS-EA remains genetically undiagnosed, which suggests the existence of novel causative CMS genes which remain uncharacterised. In light of the potential for recurrent life-threatening apnoeas in early life and the positive response to therapy, early diagnostic consideration of CMS-EA is critical, but without specific neurophysiology tests, it may go overlooked.

Messy but Fair: The ACA's Hospital Value-Based Purchasing Program and the Notice-and-Comment Process.

PubMed

Pan, Janus

2017-01-01

The Centers for Medicare and Medicaid Services (CMS) promulgated a new Medicare program called the Value-Based Purchasing Program (VBPP) as part of the 2010 Affordable Care Act (ACA). Like many other regulatory agencies, CMS used the Notice-and-Comment process to issue proposed rules, solicit public comments, and then publish final rules. Conventional literature suggests that CMS should disproportionately favor business interests during the Notice-and-Comment process, mainly due to the business interests' greater resources and capacity to draft well-reasoned comments. However, this article argues against this presumption and contends instead that CMS listens equally well to both business interest comments and private citizen comments during the formation of the VBPP. With regard to the VBPP and the ACA, CMS appears to be resisting disproportionate sway by business interests and is instead privileging the ACA's goal of improving healthcare quality.

Gamma (γ) irradiated and non-irradiated poly (L-lactide) carboxymethyl starch composite film

NASA Astrophysics Data System (ADS)

Yusof, Mohd Reusmaazran; Shamsudin, Roslinda; Abdullah, Yusof; Yaacob, Norzita

2018-04-01

A film of poly (L-lactide)(PLLA) and carboxymethyl starch (CMS) is prepared by casting evaporation method. The use of CMS blended with PLLA induces the porous film that is potentially used in tissue engineering applications. PLLA is blended with CMS in solution form and rolled on glass to produce a film. The film is then irradiated with gamma-ray (γ) at 10 and 80 kGy. FTIR analysis indicates weak interaction between PLLA and CMS at 10 kGy. Degradation and crosslinking are predicted to have occurred simultaneously at 10 kGy and massive degradation at 80 kGy as indicated in differential scanning calorimetry (DSC) curves. Mechanical analysis shows a higher strength at 10 kGy indicating that crosslinking has occured whereas degradation takes place at higher doses as shown in the reduction of mechanical strength for both PLLA and PLLA/CMS.

Gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres for gadolinium neutron-capture therapy.

PubMed

Saha, Tapan Kumar; Ichikawa, Hideki; Fukumori, Yoshinobu

2006-12-11

In order to provide a suitable device that would contain water-soluble drugs, highly water-soluble gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres (CMS-Gd-DTPA) were prepared by the emulsion method using glutaraldehyde as a cross-linker and Span 80 as a surfactant for gadolinium neutron-capture therapy of cancer. The gadolinium content and the mass median diameter of CMS-Gd-DTPA were estimated. The size and morphology of the CMS-Gd-DTPA were strongly influenced by the initial applied weight ratio of Gd-DTPA:chitosan. FTIR spectra showed that the electrostatic interaction between chitosan and Gd-DTPA accelerated the formation of gadolinium-enriched chitosan microspheres. Sufficient amounts of glutaraldehyde and Span 80 were necessary for producing discrete CMS-Gd-DTPA. The CMS-Gd-DTPA having a mass median diameter 11.7microm and 11.6% of gadolinium could be used in Gd-NCT following intratumoral injection.

45 CFR 154.230 - Submission and posting of Final Justifications for unreasonable rate increases.

Code of Federal Regulations, 2011 CFR

2011-10-01

... information available to the public on its Web site for at least three years. (d) CMS will post all Final Justifications on the CMS Web site. This information will remain available to the public on the CMS Web site for... submitted in the Preliminary Justification supporting the rate increase; and (2) Prominently post on its Web...

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

Code of Federal Regulations, 2013 CFR

2013-07-01

... CMS Recordkeeping Yes PS-8A supersedes requirements for THC CEMS. 63.10(c)(1) Additional CMS Recordkeeping Yes PS-8A supersedes requirements for THC CEMS. 63.10(c)(2)-(4) No [Reserved] 63.10(c)(5)-(8) Additional CMS Recordkeeping Yes PS-8A supersedes requirements for THC CEMS. 63.10(c)(9) No [Reserved] 63.10...

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... CMS Recordkeeping Yes PS-8A supersedes requirements for THC CEMS. 63.10(c)(1) Additional CMS Recordkeeping Yes PS-8A supersedes requirements for THC CEMS. 63.10(c)(2)-(4) No [Reserved] 63.10(c)(5)-(8) Additional CMS Recordkeeping Yes PS-8A supersedes requirements for THC CEMS. 63.10(c)(9) No [Reserved] 63.10...

42 CFR 488.433 - Civil money penalties: Uses and approval of civil money penalties imposed by CMS.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false Civil money penalties: Uses and approval of civil money penalties imposed by CMS. 488.433 Section 488.433 Public Health CENTERS FOR MEDICARE & MEDICAID... Deficiencies § 488.433 Civil money penalties: Uses and approval of civil money penalties imposed by CMS. Ten...

42 CFR 488.433 - Civil money penalties: Uses and approval of civil money penalties imposed by CMS.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false Civil money penalties: Uses and approval of civil money penalties imposed by CMS. 488.433 Section 488.433 Public Health CENTERS FOR MEDICARE & MEDICAID... Deficiencies § 488.433 Civil money penalties: Uses and approval of civil money penalties imposed by CMS. Ten...

42 CFR 488.433 - Civil money penalties: Uses and approval of civil money penalties imposed by CMS.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Civil money penalties: Uses and approval of civil money penalties imposed by CMS. 488.433 Section 488.433 Public Health CENTERS FOR MEDICARE & MEDICAID... Deficiencies § 488.433 Civil money penalties: Uses and approval of civil money penalties imposed by CMS. Ten...

Coastal Modeling System: Mathematical Formulations and Numerical Methods

DTIC Science & Technology

2014-03-01

sediment transport , and morphology change. The CMS was designed and developed for coastal inlets and navigation applications, including channel...numerical methods of hydrodynamic, salinity and sediment transport , and morphology change model CMS-Flow. The CMS- Flow uses the Finite Volume...and the influence of coastal structures. The implicit hydrodynamic model is coupled to a nonequilibrium transport model of multiple-sized total

Fermilab Education: Data-based Investigations

Science.gov Websites

Cosmic Rays Study cosmic rays with data from classrooom cosmic ray detectors. CMS e-Lab Study CMS Data using the CMS e-Lab from I2U2. LIGO Study seismic activity with data from LIGO (Laser Interferometer data from D0 - an example of conservation of momentum. Sky Server Study data from the Sloan Digital Sky

Exemption of certain systems of records under the Privacy Act. Proposed rule.

PubMed

2007-05-25

This proposed rule would exempt the four system of records from subsections (c)(3), (d)(1) through (d)(4),(e)(4)(G) and (H), and (f) of the Privacy Act pursuant to 5 U.S.C. 552a (k)(2): The Automated Survey Processing Environment (ASPEN) Complaint/Incidents Tracking System ("ACTS"), HHS/CMS, System No. 09-70-0565; the Health Insurance Portability and Accountability Act (HIPAA) Information Tracking System ("HITS"), HHS/CMS, System No. 09-70-0544; the Organ Procurement Organizations System ("OPOS"), HHS/CMS, System No. 09-70-0575; and the Fraud Investigation Database ("FID"), HHS/CMS, System No. 09-70-0527.

Exemption of certain systems of records under the Privacy Act. Final rule.

PubMed

2008-09-26

This final rule exempts four systems of records (SORs) from subsections (c)(3), (d)(1) through (d)(4), (e)(4)(G) and (H), and (f) of the Privacy Act pursuant to 5 U.S.C. 552a(k)(2): The Automated Survey Processing Environment (ASPEN) Complaint/ Incidents Tracking System (ACTS), HHS/CMS, System No. 09-70-0565; the Health Insurance Portability and Accountability Act (HIPAA) Information Tracking System (HITS), HHS/CMS, System No. 09-70-0544; the Organ Procurement Organizations System (OPOS), HHS/CMS, System No. 09-70- 0575; and the Fraud Investigation Database (FID), HHS/CMS, System No. 09-70-0527.

Synthesis and Characterization of Hyaluronic Acid Modified Colloidal Mesoporous Silica Nanoparticles

NASA Astrophysics Data System (ADS)

Zhang, Wenbiao; Wang, Yu; Li, Zhen; Wang, Wanxia; Sun, Honghao; Liu, Mingxing

2017-12-01

The colloidal mesoporous silica nanoparticles functionalized with hyaluronic acid (CMS-HA) were successfully synthesized by grafting hyaluronic acid onto the external surface of the amino-functionalized mesoporous silica nanoparticles (CMS-NH2). Moreover, the paticle properties of CMS-HA were characterized by fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS) and transmission electron microscopy (TEM). The nanomaterials were negatively charged and had a relatively uniform spherical morphology with about 100 nm in diameter, which could make it more compatible with blood. So the results suggested that the CMS-HA might be a critical nanomaterial for applying in target drug delivery system.