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

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.

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 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.

Investigation of cutaneous penetration properties of stearic acid loaded to dendritic core-multi-shell (CMS) nanocarriers.

PubMed

Lohan, S B; Icken, N; Teutloff, C; Saeidpour, S; Bittl, R; Lademann, J; Fleige, E; Haag, R; Haag, S F; Meinke, M C

2016-03-30

Dendritic core-multi shell (CMS) particles are polymer based systems consisting of a dendritic polar polyglycerol polymer core surrounded by a two-layer shell of nonpolar C18 alkyl chains and hydrophilic polyethylene glycol. Belonging to nanotransport systems (NTS) they allow the transport and storage of molecules with different chemical characters. Their amphipihilic character CMS-NTS permits good solubility in aqueous and organic solutions. We showed by multifrequency electron paramagnetic resonance (EPR) spectroscopy that spin-labeled 5-doxyl stearic acid (5DSA) can be loaded into the CMS-NTS. Furthermore, the release of 5DSA from the carrier into the stratum corneum of porcine skin was monitored ex vivo by EPR spectroscopy. Additionally, the penetration of the CMS-NTS into the skin was analyzed by fluorescence microscopy using indocarbocyanine (ICC) covalently bound to the nanocarrier. Thereby, no transport into the viable skin was observed, whereas the CMS-NTS had penetrated into the hair follicles down to a depth of 340 μm ± 82 μm. Thus, it could be shown that the combined application of fluorescence microscopy and multi-frequency EPR spectroscopy can be an efficient tool for investigating the loading of spin labeled drugs to nanocarrier systems, drug release and penetration into the skin as well as the localization of the NTS in the skin. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Proteomic analysis reveals strong mitochondrial involvement in cytoplasmic male sterility of pepper (Capsicum annuum L.).

PubMed

Guo, Jinju; Wang, Peng; Cheng, Qing; Sun, Limin; Wang, Hongyu; Wang, Yutong; Kao, Lina; Li, Yanan; Qiu, Tuoyu; Yang, Wencai; Shen, Huolin

2017-09-25

Although cytoplasmic male sterility (CMS) is widely used for developing pepper hybrids, its molecular mechanism remains unclear. In this study, we used a high-throughput proteomics method called label-free to compare protein abundance across a pepper CMS line (A-line) and its isogenic maintainer line (B-line). Data are available via ProteomeXchange with identifier PXD006104. Approximately 324 differentially abundant protein species were identified and quantified; among which, 47 were up-accumulated and 140 were down-accumulated in the A-line; additionally, 75 and 62 protein species were specifically accumulated in the A-line and B-line, respectively. Protein species involved in pollen exine formation, pyruvate metabolic processes, the tricarboxylic acid cycle, the mitochondrial electron transport chain, and oxidative stress response were observed to be differentially accumulated between A-line and B-line, suggesting their potential roles in the regulation of pepper pollen abortion. Based on our data, we proposed a potential regulatory network for pepper CMS that unifies these processes. Artificial emasculation is a major obstacle in pepper hybrid breeding for its high labor cost and poor seed purity. While the use of cytoplasmic male sterility (CMS) in hybrid system is seriously frustrated because a long time is needed to cultivate male sterility line and its isogenic restore line. Transgenic technology is an effective and rapid method to obtain male sterility lines and its widely application has very important significance in speeding up breeding process in pepper. Although numerous studies have been conducted to select the genes related to male sterility, the molecular mechanism of cytoplasmic male sterility in pepper remains unknown. In this study, we used the high-throughput proteomic method called "label-free", coupled with liquid chromatography-quadrupole mass spectrometry (LC-MS/MS), to perform a novel comparison of expression profiles in a CMS pepper line and its maintainer line. Based on our results, we proposed a potential regulated protein network involved in pollen development as a novel mechanism of pepper CMS. Copyright © 2017. Published by Elsevier B.V.

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.

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 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.

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.

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.

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

Further Developments of BEM for Micro and Macromechanical Analyses of Composites: Boundary Element Software Technology-Composite User's Manual

NASA Technical Reports Server (NTRS)

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

1997-01-01

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. A brief review of the theoretical background is presented for each analysis category. Then, Chapter 3 discusses the key aspects of the numerical implementation, while Chapter 4 provides a tutorial for the beginning BEST-CMS user. The heart of the manual, however, is in Chapter 5, 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 6 includes sample problems and should be of considerable assistance to the novice. Chapter 7 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 8 contains a detailed 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 9.

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.

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.

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

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.

75 FR 76988 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-10

... Enrollment, Chain and Ownership System (PECOS) Security Consent Form; Use: The primary function of the... for the proper performance of the agency's functions; (2) the accuracy of the estimated burden; (3... the primary document used by CMS in developing the national Medicaid budget estimates that are...

Storage element performance optimization for CMS analysis jobs

NASA Astrophysics Data System (ADS)

Behrmann, G.; Dahlblom, J.; Guldmyr, J.; Happonen, K.; Lindén, T.

2012-12-01

Tier-2 computing sites in the Worldwide Large Hadron Collider Computing Grid (WLCG) host CPU-resources (Compute Element, CE) and storage resources (Storage Element, SE). The vast amount of data that needs to processed from the Large Hadron Collider (LHC) experiments requires good and efficient use of the available resources. Having a good CPU efficiency for the end users analysis jobs requires that the performance of the storage system is able to scale with I/O requests from hundreds or even thousands of simultaneous jobs. In this presentation we report on the work on improving the SE performance at the Helsinki Institute of Physics (HIP) Tier-2 used for the Compact Muon Experiment (CMS) at the LHC. Statistics from CMS grid jobs are collected and stored in the CMS Dashboard for further analysis, which allows for easy performance monitoring by the sites and by the CMS collaboration. As part of the monitoring framework CMS uses the JobRobot which sends every four hours 100 analysis jobs to each site. CMS also uses the HammerCloud tool for site monitoring and stress testing and it has replaced the JobRobot. The performance of the analysis workflow submitted with JobRobot or HammerCloud can be used to track the performance due to site configuration changes, since the analysis workflow is kept the same for all sites and for months in time. The CPU efficiency of the JobRobot jobs at HIP was increased approximately by 50 % to more than 90 %, by tuning the SE and by improvements in the CMSSW and dCache software. The performance of the CMS analysis jobs improved significantly too. Similar work has been done on other CMS Tier-sites, since on average the CPU efficiency for CMSSW jobs has increased during 2011. Better monitoring of the SE allows faster detection of problems, so that the performance level can be kept high. The next storage upgrade at HIP consists of SAS disk enclosures which can be stress tested on demand with HammerCloud workflows, to make sure that the I/O-performance is good.

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.

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.

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 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.

Predictors of chain acquisition among independent dialysis facilities.

PubMed

Pozniak, Alyssa S; Hirth, Richard A; Banaszak-Holl, Jane; Wheeler, John R C

2010-04-01

To determine the predictors of chain acquisition among independent dialysis providers. Retrospective facility-level data combined from CMS Cost Reports, Medical Evidence Forms, Annual Facility Surveys, and claims for 1996-2003. Independent dialysis facilities' probability of acquisition by a dialysis chain (overall and by chain size) was estimated using a discrete time hazard rate model, controlling for financial and clinical performance, practice patterns, market factors, and other facility characteristics. The sample includes all U.S. freestanding dialysis facilities that report not being chain affiliated for at least 1 year between 1997 and 2003. Above-average costs and better quality outcomes are significant determinants of dialysis chain acquisition. Facilities in larger markets were more likely to be acquired by a chain. Furthermore, small dialysis chains have different acquisition strategies than large chains. Dialysis chains appear to employ a mix of turn-around and cream-skimming strategies. Poor financial health is a predictor of chain acquisition as in other health care sectors, but the increased likelihood of chain acquisition among higher quality facilities is unique to the dialysis industry. Significant differences among predictors of acquisition by small and large chains reinforce the importance of using a richer classification for chain status.

Synergy of imipenem/colistin methanesulfonate combinations against imipenem-nonsusceptible multidrug-resistant Acinetobacter baumannii.

PubMed

Leu, Hsieh-Shong; Ye, Jung-Jr; Lee, Ming-Hsun; Su, Lin-Hui; Huang, Po-Yen; Wu, Tsu-Lan; Huang, Ching-Tai

2014-10-01

The optimal combination ratio of imipenem to colistin methanesulfonate (CMS) against imipenem-nonsusceptible multidrug-resistant Acinetobacter baumannii (INS-MDRAB) has not been determined in previous studies. To provide an alternative therapeutic option for clinical INS-MDRAB isolates, we investigated whether clinically achievable serum concentrations of CMS in combination with imipenem enhance the in vitro activity of imipenem against the INS-MDRAB isolates. Fifty-nine INS-MDRAB isolates with imipenem minimal inhibitory concentration (MIC) values of ≥8 mg/L were selected randomly from the Clinical Microbiology Laboratory at a university-affiliated medical center between July 1998 and May 2005. The in vitro activity of imipenem among these 59 clinical isolates was explored via serial two-fold dilutions containing a range of imipenem concentration from 0.125 mg/L to 256 mg/L, in combination with two fixed CMS concentrations at 0.5 mg/L and 1 mg/L. Genotype classification was performed using the pulsed-field gel electrophoresis method and infrequent-restriction-site polymerase chain reaction. A significant reversal of imipenem resistance (i.e., MICs ≤ 4 mg/L) was observed in 34 (57.6%) isolates and 44 (74.6%) isolates with the tests of CMS concentrations at 0.5 mg/L and 1 mg/L, respectively (p = 0.041). Genotype 1 was predominant (43 isolates, 72.9%) with imipenem resistance reversal rates of 51.2% and 79.1% (p = 0.004) in the tests of CMS at 0.5 mg/L and 1 mg/L, respectively. The synergy of imipenem/CMS against INS-MDRAB was significantly better for the CMS concentration at 1 mg/L than that at 0.5 mg/L, especially in our predominant clone. Our results provided insightful information for treating INS-MDRAB infections in clinical practice. Copyright © 2013. Published by Elsevier B.V.

Anisotropic microfibrous scaffolds enhance the organization and function of cardiomyocytes derived from induced pluripotent stem cells.

PubMed

Wanjare, Maureen; Hou, Luqia; Nakayama, Karina H; Kim, Joseph J; Mezak, Nicholas P; Abilez, Oscar J; Tzatzalos, Evangeline; Wu, Joseph C; Huang, Ngan F

2017-07-25

Engineering of myocardial tissue constructs is a promising approach for treatment of coronary heart disease. To engineer myocardial tissues that better mimic the highly ordered physiological arrangement and function of native cardiomyocytes, we generated electrospun microfibrous polycaprolactone scaffolds with either randomly oriented (14 μm fiber diameter) or parallel-aligned (7 μm fiber diameter) microfiber arrangement and co-seeded the scaffolds with human induced pluripotent stem cell-derived cardiomyocytes (iCMs) and endothelial cells (iECs) for up to 12 days after iCM seeding. Here we demonstrated that aligned microfibrous scaffolds induced iCM alignment along the direction of the aligned microfibers after 2 days of iCM seeding, as well as promoted greater iCM maturation by increasing the sarcomeric length and gene expression of myosin heavy chain adult isoform (MYH7), in comparison to randomly oriented scaffolds. Furthermore, the benefit of scaffold anisotropy was evident in the significantly higher maximum contraction velocity of iCMs on the aligned scaffolds, compared to randomly oriented scaffolds, at 12 days of culture. Co-seeding of iCMs with iECs led to reduced contractility, compared to when iCMs were seeded alone. These findings demonstrate a dominant role of scaffold anisotropy in engineering cardiovascular tissues that maintain iCM organization and contractile function.

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

The diverse use of clouds by CMS

DOE PAGES

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

2015-12-23

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

The Status of the Cms Experiment

NASA Astrophysics Data System (ADS)

Green, Dan

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

High-Content Electrophysiological Analysis of Human Pluripotent Stem Cell-Derived Cardiomyocytes (hPSC-CMs).

PubMed

Kong, Chi-Wing; Geng, Lin; Li, Ronald A

2018-01-01

Considerable interest has been raised to develop human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) as a model for drug discovery and cardiotoxicity screening. High-content electrophysiological analysis of currents generated by transmembrane cell surface ion channels has been pursued to complement such emerging applications. Here we describe practical procedures and considerations for accomplishing successful assays of hPSC-CMs using an automated planar patch-clamp system.

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

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 ...

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

PubMed

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

2016-06-01

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

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

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...

CMS Configuration Editor: GUI based application for user analysis job

NASA Astrophysics Data System (ADS)

de Cosa, A.

2011-12-01

We present the user interface and the software architecture of the Configuration Editor for the CMS experiment. The analysis workflow is organized in a modular way integrated within the CMS framework that organizes in a flexible way user analysis code. The Python scripting language is adopted to define the job configuration that drives the analysis workflow. It could be a challenging task for users, especially for newcomers, to develop analysis jobs managing the configuration of many required modules. For this reason a graphical tool has been conceived in order to edit and inspect configuration files. A set of common analysis tools defined in the CMS Physics Analysis Toolkit (PAT) can be steered and configured using the Config Editor. A user-defined analysis workflow can be produced starting from a standard configuration file, applying and configuring PAT tools according to the specific user requirements. CMS users can adopt this tool, the Config Editor, to create their analysis visualizing in real time which are the effects of their actions. They can visualize the structure of their configuration, look at the modules included in the workflow, inspect the dependences existing among the modules and check the data flow. They can visualize at which values parameters are set and change them according to what is required by their analysis task. The integration of common tools in the GUI needed to adopt an object-oriented structure in the Python definition of the PAT tools and the definition of a layer of abstraction from which all PAT tools inherit.

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.

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

WLCG scale testing during CMS data challenges

NASA Astrophysics Data System (ADS)

Gutsche, O.; Hajdu, C.

2008-07-01

The CMS computing model to process and analyze LHC collision data follows a data-location driven approach and is using the WLCG infrastructure to provide access to GRID resources. As a preparation for data taking, CMS tests its computing model during dedicated data challenges. An important part of the challenges is the test of the user analysis which poses a special challenge for the infrastructure with its random distributed access patterns. The CMS Remote Analysis Builder (CRAB) handles all interactions with the WLCG infrastructure transparently for the user. During the 2006 challenge, CMS set its goal to test the infrastructure at a scale of 50,000 user jobs per day using CRAB. Both direct submissions by individual users and automated submissions by robots were used to achieve this goal. A report will be given about the outcome of the user analysis part of the challenge using both the EGEE and OSG parts of the WLCG. In particular, the difference in submission between both GRID middlewares (resource broker vs. direct submission) will be discussed. In the end, an outlook for the 2007 data challenge is given.

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.

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.

Predictors of Chain Acquisition among Independent Dialysis Facilities

PubMed Central

Pozniak, Alyssa S; Hirth, Richard A; Banaszak-Holl, Jane; Wheeler, John R C

2010-01-01

Objective To determine the predictors of chain acquisition among independent dialysis providers. Data Sources Retrospective facility-level data combined from CMS Cost Reports, Medical Evidence Forms, Annual Facility Surveys, and claims for 1996–2003. Study Design Independent dialysis facilities' probability of acquisition by a dialysis chain (overall and by chain size) was estimated using a discrete time hazard rate model, controlling for financial and clinical performance, practice patterns, market factors, and other facility characteristics. Data Collection The sample includes all U.S. freestanding dialysis facilities that report not being chain affiliated for at least 1 year between 1997 and 2003. Principal Findings Above-average costs and better quality outcomes are significant determinants of dialysis chain acquisition. Facilities in larger markets were more likely to be acquired by a chain. Furthermore, small dialysis chains have different acquisition strategies than large chains. Conclusions Dialysis chains appear to employ a mix of turn-around and cream-skimming strategies. Poor financial health is a predictor of chain acquisition as in other health care sectors, but the increased likelihood of chain acquisition among higher quality facilities is unique to the dialysis industry. Significant differences among predictors of acquisition by small and large chains reinforce the importance of using a richer classification for chain status. PMID:20148985

Origin of the different transport properties of electron and hole polarons in an ambipolar polyselenophene-based conjugated polymer

NASA Astrophysics Data System (ADS)

Chen, Zhuoying; Bird, Matthew; Lemaur, Vincent; Radtke, Guillaume; Cornil, Jérôme; Heeney, Martin; McCulloch, Iain; Sirringhaus, Henning

2011-09-01

Understanding the mechanisms limiting ambipolar transport in conjugated polymer field-effect transistors (FETs) is of both fundamental and practical interest. Here, we present a systematic study comparing hole and electron charge transport in an ambipolar conjugated polymer, semicrystalline poly(3,3''-di-n-decylterselenophene) (PSSS). Starting from a detailed analysis of the device characteristics and temperature/charge-density dependence of the mobility, we interpret the difference between hole and electron transport through both the Vissenberg-Matters and the mobility-edge model. To obtain microscopic insight into the quantum mechanical wave function of the charges at a molecular level, we combine charge modulation spectroscopy (CMS) measuring the charge-induced absorption signatures from positive and negative polarons in these ambipolar FETs with corresponding density functional theory (DFT) calculations. We observe a significantly higher switch-on voltage for electrons than for holes due to deep electron trap states, but also a higher activation energy of the mobility for mobile electrons. The CMS spectra reveal that the electrons that remain mobile and contribute to the FET current have a wave function that is more localized onto a single polymer chain than that of holes, which is extended over several polymer chains. We interpret this as evidence that the transport properties of the mobile electrons in PSSS are still affected by the presence of deep electron traps. The more localized electron state could be due to the mobile electrons interacting with shallow trap states in the vicinity of a chemical, potentially water-related, impurity that might precede the capture of the electron into a deeply trapped state.

Comprehensive transcriptome-based characterization of differentially expressed genes involved in microsporogenesis of radish CMS line and its maintainer.

PubMed

Xie, Yang; Zhang, Wei; Wang, Yan; Xu, Liang; Zhu, Xianwen; Muleke, Everlyne M; Liu, Liwang

2016-09-01

Microsporogenesis is an indispensable period for investigating microspore development and cytoplasmic male sterility (CMS) occurrence. Radish CMS line plays a critical role in elite F1 hybrid seed production and heterosis utilization. However, the molecular mechanisms of microspore development and CMS occurrence have not been thoroughly uncovered in radish. In this study, a comparative analysis of radish floral buds from a CMS line (NAU-WA) and its maintainer (NAU-WB) was conducted using next generation sequencing (NGS) technology. Digital gene expression (DGE) profiling revealed that 3504 genes were significantly differentially expressed between NAU-WA and NAU-WB library, among which 1910 were upregulated and 1594 were downregulated. Gene ontology (GO) analysis showed that these differentially expressed genes (DEGs) were mainly enriched in extracellular region, catalytic activity, and response to stimulus. KEGG enrichment analysis revealed that the DEGs were predominantly associated with flavonoid biosynthesis, glycolysis, and biosynthesis of secondary metabolites. Real-time quantitative PCR analysis showed that the expression profiles of 13 randomly selected DEGs were in high agreement with results from Illumina sequencing. Several candidate genes encoding ATP synthase, auxin response factor (ARF), transcription factors (TFs), chalcone synthase (CHS), and male sterility (MS) were responsible for microsporogenesis. Furthermore, a schematic diagram for functional interaction of DEGs from NAU-WA vs. NAU-WB library in radish plants was proposed. These results could provide new information on the dissection of the molecular mechanisms underlying microspore development and CMS occurrence in radish.

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.

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.

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.

Stability and Scalability of the CMS Global Pool: Pushing HTCondor and GlideinWMS to New Limits

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

Balcas, J.; Bockelman, B.; Hufnagel, D.

The CMS Global Pool, based on HTCondor and glideinWMS, is the main computing resource provisioning system for all CMS workflows, including analysis, Monte Carlo production, and detector data reprocessing activities. The total resources at Tier-1 and Tier-2 grid sites pledged to CMS exceed 100,000 CPU cores, while another 50,000 to 100,000 CPU cores are available opportunistically, pushing the needs of the Global Pool to higher scales each year. These resources are becoming more diverse in their accessibility and configuration over time. Furthermore, the challenge of stably running at higher and higher scales while introducing new modes of operation such asmore » multi-core pilots, as well as the chaotic nature of physics analysis workflows, places huge strains on the submission infrastructure. This paper details some of the most important challenges to scalability and stability that the CMS Global Pool has faced since the beginning of the LHC Run II and how they were overcome.« less

Stability and scalability of the CMS Global Pool: Pushing HTCondor and glideinWMS to new limits

NASA Astrophysics Data System (ADS)

Balcas, J.; Bockelman, B.; Hufnagel, D.; Hurtado Anampa, K.; Aftab Khan, F.; Larson, K.; Letts, J.; Marra da Silva, J.; Mascheroni, M.; Mason, D.; Perez-Calero Yzquierdo, A.; Tiradani, A.

2017-10-01

The CMS Global Pool, based on HTCondor and glideinWMS, is the main computing resource provisioning system for all CMS workflows, including analysis, Monte Carlo production, and detector data reprocessing activities. The total resources at Tier-1 and Tier-2 grid sites pledged to CMS exceed 100,000 CPU cores, while another 50,000 to 100,000 CPU cores are available opportunistically, pushing the needs of the Global Pool to higher scales each year. These resources are becoming more diverse in their accessibility and configuration over time. Furthermore, the challenge of stably running at higher and higher scales while introducing new modes of operation such as multi-core pilots, as well as the chaotic nature of physics analysis workflows, places huge strains on the submission infrastructure. This paper details some of the most important challenges to scalability and stability that the CMS Global Pool has faced since the beginning of the LHC Run II and how they were overcome.

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.

Scaling up a CMS tier-3 site with campus resources and a 100 Gb/s network connection: what could go wrong?

NASA Astrophysics Data System (ADS)

Wolf, Matthias; Woodard, Anna; Li, Wenzhao; Hurtado Anampa, Kenyi; Tovar, Benjamin; Brenner, Paul; Lannon, Kevin; Hildreth, Mike; Thain, Douglas

2017-10-01

The University of Notre Dame (ND) CMS group operates a modest-sized Tier-3 site suitable for local, final-stage analysis of CMS data. However, through the ND Center for Research Computing (CRC), Notre Dame researchers have opportunistic access to roughly 25k CPU cores of computing and a 100 Gb/s WAN network link. To understand the limits of what might be possible in this scenario, we undertook to use these resources for a wide range of CMS computing tasks from user analysis through large-scale Monte Carlo production (including both detector simulation and data reconstruction.) We will discuss the challenges inherent in effectively utilizing CRC resources for these tasks and the solutions deployed to overcome them.

Water and solute permeability of rat lung caveolae: high permeabilities explained by acyl chain unsaturation.

PubMed

Hill, Warren G; Almasri, Eyad; Ruiz, W Giovanni; Apodaca, Gerard; Zeidel, Mark L

2005-07-01

Caveolae are invaginated membrane structures with high levels of cholesterol, sphingomyelin, and caveolin protein that are predicted to exist as liquid-ordered domains with low water permeability. We isolated a caveolae-enriched membrane fraction without detergents from rat lung and characterized its permeability properties to nonelectrolytes and protons. Membrane permeability to water was 2.85 +/- 0.41 x 10(-3) cm/s, a value 5-10 times higher than expected based on comparisons with other cholesterol and sphingolipid-enriched membranes. Permeabilities to urea, ammonia, and protons were measured and found to be moderately high for urea and ammonia at 8.85 +/- 2.40 x 10(-7)and 6.84 +/- 1.03 x 10(-2) respectively and high for protons at 8.84 +/- 3.06 x 10(-2) cm/s. To examine whether caveolin or other integral membrane proteins were responsible for high permeabilities, liposomes designed to mimic the lipids of the inner and outer leaflets of the caveolar membrane were made. Osmotic water permeability to both liposome compositions were determined and a combined inner/outer leaflet water permeability was calculated and found to be close to that of native caveolae at 1.58 +/- 1.1 x 10(-3) cm/s. In caveolae, activation energy for water flux was high (19.4 kcal/mol) and water permeability was not inhibited by HgCl2; however, aquaporin 1 was detectable by immunoblotting. Immunostaining of rat lung with AQP1 and caveolin antisera revealed very low levels of colocalization. We conclude that aquaporin water channels do not contribute significantly to the observed water flux and that caveolae have relatively high water and solute permeabilities due to the high degree of unsaturation in their fatty acyl chains.

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.

Transcriptome profiling and cataloging differential gene expression in floral buds of fertile and sterile lines of cotton (Gossypium hirsutum L.).

PubMed

Hamid, Rasmieh; Tomar, Rukam S; Marashi, Hassan; Shafaroudi, Saeid Malekzadeh; Golakiya, Balaji A; Mohsenpour, Motahhareh

2018-06-20

Cytoplasmic Male Sterility is maternally inherited trait in plants, characterized by failure to produce functional pollen during anther development. Anther development is modulated through the interaction of nuclear and mitochondrial genes. In the present study, differential gene expression of floral buds at the sporogenous stage (SS) and microsporocyte stage (MS) between CGMS and its fertile maintainer line of cotton plants was studied. A total of 320 significantly differentially expressed genes, including 20 down-regulated and 37 up-regulated in CGMS comparing with its maintainer line at the SS stage, as well as and 89 down-regulated and 4 up-regulated in CGMS compared to the fertile line at MS stage. Comparing the two stages in the same line, there were 6 down-regulated differentially expressed genes only induced in CGMS and 9 up-regulated differentially expressed gene only induced in its maintainer. GO analysis revealed essential genes responsible for pollen development, and cytoskeleton category show differential expression between the fertile and CGMS lines. Validation studies by qRT-PCR shows concordance with RNA-seq result. A set of novel SSRs identified in this study can be used in evaluating genetic relationships among cultivars, QTL mapping, and marker-assisted breeding. We reported aberrant expression of genes related to pollen exine formation, and synthesis of pectin lyase, myosine heavy chain, tubulin, actin-beta, heat shock protein and myeloblastosis (MYB) protein as targets for CMS in cotton. The results of this study contribute to basic information for future screening of genes and identification of molecular portraits responsible for CMS as well as to elucidate molecular mechanisms that lead to CMS in cotton. Copyright © 2018 Elsevier B.V. All rights reserved.

Genome-wide comparative transcriptome analysis of CMS-D2 and its maintainer and restorer lines in upland cotton.

PubMed

Wu, Jianyong; Zhang, Meng; Zhang, Bingbing; Zhang, Xuexian; Guo, Liping; Qi, Tingxiang; Wang, Hailin; Zhang, Jinfa; Xing, Chaozhu

2017-06-08

Cytoplasmic male sterility (CMS) conferred by the cytoplasm from Gossypium harknessii (D2) is an important system for hybrid seed production in Upland cotton (G. hirsutum). The male sterility of CMS-D2 (i.e., A line) can be restored to fertility by a restorer (i.e., R line) carrying the restorer gene Rf1 transferred from the D2 nuclear genome. However, the molecular mechanisms of CMS-D2 and its restoration are poorly understood. In this study, a genome-wide comparative transcriptome analysis was performed to identify differentially expressed genes (DEGs) in flower buds among the isogenic fertile R line and sterile A line derived from a backcross population (BC 8 F 1 ) and the recurrent parent, i.e., the maintainer (B line). A total of 1464 DEGs were identified among the three isogenic lines, and the Rf1-carrying Chr_D05 and its homeologous Chr_A05 had more DEGs than other chromosomes. The results of GO and KEGG enrichment analysis showed differences in circadian rhythm between the fertile and sterile lines. Eleven DEGs were selected for validation using qRT-PCR, confirming the accuracy of the RNA-seq results. Through genome-wide comparative transcriptome analysis, the differential expression profiles of CMS-D2 and its maintainer and restorer lines in Upland cotton were identified. Our results provide an important foundation for further studies into the molecular mechanisms of the interactions between the restorer gene Rf1 and the CMS-D2 cytoplasm.

Theoretical analysis of HVAC duct hanger systems

NASA Technical Reports Server (NTRS)

Miller, R. D.

1987-01-01

Several methods are presented which, together, may be used in the analysis of duct hanger systems over a wide range of frequencies. The finite element method (FEM) and component mode synthesis (CMS) method are used for low- to mid-frequency range computations and have been shown to yield reasonably close results. The statistical energy analysis (SEA) method yields predictions which agree with the CMS results for the 800 to 1000 Hz range provided that a sufficient number of modes participate. The CMS approach has been shown to yield valuable insight into the mid-frequency range of the analysis. It has been demonstrated that it is possible to conduct an analysis of a duct/hanger system in a cost-effective way for a wide frequency range, using several methods which overlap for several frequency bands.

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.

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.

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.

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.

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.

3D aggregate culture improves metabolic maturation of human pluripotent stem cell derived cardiomyocytes.

PubMed

Correia, Cláudia; Koshkin, Alexey; Duarte, Patrícia; Hu, Dongjian; Carido, Madalena; Sebastião, Maria J; Gomes-Alves, Patrícia; Elliott, David A; Domian, Ibrahim J; Teixeira, Ana P; Alves, Paula M; Serra, Margarida

2018-03-01

Three-dimensional (3D) cultures of human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) hold great promise for drug discovery, providing a better approximation to the in vivo physiology over standard two-dimensional (2D) monolayer cultures. However, the transition of CM differentiation protocols from 2D to 3D cultures is not straightforward. In this work, we relied on the aggregation of hPSC-derived cardiac progenitors and their culture under agitated conditions to generate highly pure cardiomyocyte aggregates. Whole-transcriptome analysis and 13 C-metabolic flux analysis allowed to demonstrate at both molecular and fluxome levels that such 3D culture environment enhances metabolic maturation of hiPSC-CMs. When compared to 2D, 3D cultures of hiPSC-CMs displayed down-regulation of genes involved in glycolysis and lipid biosynthesis and increased expression of genes involved in OXPHOS. Accordingly, 3D cultures of hiPSC-CMs had lower fluxes through glycolysis and fatty acid synthesis and increased TCA-cycle activity. Importantly, we demonstrated that the 3D culture environment reproducibly improved both CM purity and metabolic maturation across different hPSC lines, thereby providing a robust strategy to derive enriched hPSC-CMs with metabolic features closer to that of adult CMs. © 2017 Wiley Periodicals, Inc.

Personalizing Chinese medicine by integrating molecular features of diseases and herb ingredient information: application to acute myeloid leukemia

PubMed Central

Xie, Duoli; Shi, Tieliu; Wen, Chengping

2017-01-01

Traditional Chinese Medicine (TCM) has been widely used as a complementary medicine in Acute Myeloid Leukemia (AML) treatment. In this study, we proposed a new classification of Chinese Medicines (CMs) by integrating the latest discoveries in disease molecular mechanisms and traditional medicine theory. We screened out a set of chemical compounds on basis of AML differential expression genes and chemical-protein interactions and then mapped them to Traditional Chinese Medicine Integrated Database. 415 CMs contain those compounds and they were categorized into 8 groups according to the Traditional Chinese Pharmacology. Pathway analysis and synthetic lethality gene pairs were applied to analyze the dissimilarity, generality and intergroup relations of different groups. We defined hub CM pairs and alternative CM groups based on the analysis result and finally proposed a formula to form an effective anti-AML prescription which combined the hub CM pairs with alternative CMs according to patients’ molecular features. Our method of formulating CMs based on patients’ stratification provides novel insights into the new usage of conventional CMs and will promote TCM modernization. PMID:28454110

Personalizing Chinese medicine by integrating molecular features of diseases and herb ingredient information: application to acute myeloid leukemia.

PubMed

Huang, Lin; Li, Haichang; Xie, Duoli; Shi, Tieliu; Wen, Chengping

2017-06-27

Traditional Chinese Medicine (TCM) has been widely used as a complementary medicine in Acute Myeloid Leukemia (AML) treatment. In this study, we proposed a new classification of Chinese Medicines (CMs) by integrating the latest discoveries in disease molecular mechanisms and traditional medicine theory. We screened out a set of chemical compounds on basis of AML differential expression genes and chemical-protein interactions and then mapped them to Traditional Chinese Medicine Integrated Database. 415 CMs contain those compounds and they were categorized into 8 groups according to the Traditional Chinese Pharmacology. Pathway analysis and synthetic lethality gene pairs were applied to analyze the dissimilarity, generality and intergroup relations of different groups. We defined hub CM pairs and alternative CM groups based on the analysis result and finally proposed a formula to form an effective anti-AML prescription which combined the hub CM pairs with alternative CMs according to patients' molecular features. Our method of formulating CMs based on patients' stratification provides novel insights into the new usage of conventional CMs and will promote TCM modernization.

Effect of microwave treatment on structure of binders based on sodium carboxymethyl starch: FT-IR, FT-Raman and XRD investigations

NASA Astrophysics Data System (ADS)

Kaczmarska, Karolina; Grabowska, Beata; Spychaj, Tadeusz; Zdanowicz, Magdalena; Sitarz, Maciej; Bobrowski, Artur; Cukrowicz, Sylwia

2018-06-01

The paper deals with the influence of the microwave treatment on sodium carboxymethyl starch (CMS-Na) applied as a binder for moulding sands. The Fourier transformation infrared spectrometry (FT-IR), Raman spectroscopy (FT-Raman) and XRD analysis data of native potato starch and three different carboxymethyl starches (CMS-Na) with various degree of substitution (DS) before and after exposition to microwave radiation have been compared. FT-IR studies showed that polar groups present in CMS-Na structure take part in the formation of new hydrogen bonds network after water evaporation. However, these changes depend on DS value of the modified starch. The FT-Raman study confirmed that due to the impact on the samples by microwave, the changes of intensity in the characteristic bands associated with the crystalline regions in the sample were noticed. The X-ray diffraction data for microwave treated CMS-Na samples have been compared with the diffractograms of initial materials and analysis of XRD patterns confirmed that microwave-treated samples exhibit completely amorphous structure. Analysis of structural changes allows to state that the binding of sand grains in moulding sand with CMS-Na polymeric binder consists in the formation of hydrogen bonds networks (physical cross-linking).

Effect of microwave treatment on structure of binders based on sodium carboxymethyl starch: FT-IR, FT-Raman and XRD investigations.

PubMed

Kaczmarska, Karolina; Grabowska, Beata; Spychaj, Tadeusz; Zdanowicz, Magdalena; Sitarz, Maciej; Bobrowski, Artur; Cukrowicz, Sylwia

2018-06-15

The paper deals with the influence of the microwave treatment on sodium carboxymethyl starch (CMS-Na) applied as a binder for moulding sands. The Fourier transformation infrared spectrometry (FT-IR), Raman spectroscopy (FT-Raman) and XRD analysis data of native potato starch and three different carboxymethyl starches (CMS-Na) with various degree of substitution (DS) before and after exposition to microwave radiation have been compared. FT-IR studies showed that polar groups present in CMS-Na structure take part in the formation of new hydrogen bonds network after water evaporation. However, these changes depend on DS value of the modified starch. The FT-Raman study confirmed that due to the impact on the samples by microwave, the changes of intensity in the characteristic bands associated with the crystalline regions in the sample were noticed. The X-ray diffraction data for microwave treated CMS-Na samples have been compared with the diffractograms of initial materials and analysis of XRD patterns confirmed that microwave-treated samples exhibit completely amorphous structure. Analysis of structural changes allows to state that the binding of sand grains in moulding sand with CMS-Na polymeric binder consists in the formation of hydrogen bonds networks (physical cross-linking). Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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.

CMS endcap RPC performance analysis

NASA Astrophysics Data System (ADS)

Teng, H.; CMS Collaboration

2014-08-01

The Resistive Plate Chamber (RPC) detector system in LHC-CMS experiment is designed for the trigger purpose. The endcap RPC system has been successfully operated since the commissioning period (2008) to the end of RUN1 (2013). We have developed an analysis tool for endcap RPC performance and validated the efficiency calculation algorithm, focusing on the first endcap station which was assembled and tested by the Peking University group. We cross checked the results obtained with those extracted with alternative methods and we found good agreement in terms of performance parameters [1]. The results showed that the CMS-RPC endcap system fulfilled the performance expected in the Technical Design Report [2].

Novel Analysis Software for Detecting and Classifying Ca2+ Transient Abnormalities in Stem Cell-Derived Cardiomyocytes

PubMed Central

Penttinen, Kirsi; Siirtola, Harri; Àvalos-Salguero, Jorge; Vainio, Tiina; Juhola, Martti; Aalto-Setälä, Katriina

2015-01-01

Comprehensive functioning of Ca2+ cycling is crucial for excitation–contraction coupling of cardiomyocytes (CMs). Abnormal Ca2+ cycling is linked to arrhythmogenesis, which is associated with cardiac disorders and heart failure. Accordingly, we have generated spontaneously beating CMs from induced pluripotent stem cells (iPSC) derived from patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), which is an inherited and severe cardiac disease. Ca2+ cycling studies have revealed substantial abnormalities in these CMs. Ca2+ transient analysis performed manually lacks accepted analysis criteria, and has both low throughput and high variability. To overcome these issues, we have developed a software tool, AnomalyExplorer based on interactive visualization, to assist in the classification of Ca2+ transient patterns detected in CMs. Here, we demonstrate the usability and capability of the software, and we also compare the analysis efficiency to manual analysis. We show that AnomalyExplorer is suitable for detecting normal and abnormal Ca2+ transients; furthermore, this method provides more defined and consistent information regarding the Ca2+ abnormality patterns and cell line specific differences when compared to manual analysis. This tool will facilitate and speed up the analysis of CM Ca2+ transients, making it both more accurate and user-independent. AnomalyExplorer can be exploited in Ca2+ cycling analysis to study basic disease pathology and the effects of different drugs. PMID:26308621

Novel Analysis Software for Detecting and Classifying Ca2+ Transient Abnormalities in Stem Cell-Derived Cardiomyocytes.

PubMed

Penttinen, Kirsi; Siirtola, Harri; Àvalos-Salguero, Jorge; Vainio, Tiina; Juhola, Martti; Aalto-Setälä, Katriina

2015-01-01

Comprehensive functioning of Ca2+ cycling is crucial for excitation-contraction coupling of cardiomyocytes (CMs). Abnormal Ca2+ cycling is linked to arrhythmogenesis, which is associated with cardiac disorders and heart failure. Accordingly, we have generated spontaneously beating CMs from induced pluripotent stem cells (iPSC) derived from patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), which is an inherited and severe cardiac disease. Ca2+ cycling studies have revealed substantial abnormalities in these CMs. Ca2+ transient analysis performed manually lacks accepted analysis criteria, and has both low throughput and high variability. To overcome these issues, we have developed a software tool, AnomalyExplorer based on interactive visualization, to assist in the classification of Ca2+ transient patterns detected in CMs. Here, we demonstrate the usability and capability of the software, and we also compare the analysis efficiency to manual analysis. We show that AnomalyExplorer is suitable for detecting normal and abnormal Ca2+ transients; furthermore, this method provides more defined and consistent information regarding the Ca2+ abnormality patterns and cell line specific differences when compared to manual analysis. This tool will facilitate and speed up the analysis of CM Ca2+ transients, making it both more accurate and user-independent. AnomalyExplorer can be exploited in Ca2+ cycling analysis to study basic disease pathology and the effects of different drugs.

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.

Comparative analysis of mitochondrial genomes between a wheat K-type cytoplasmic male sterility (CMS) line and its maintainer line.

PubMed

Liu, Huitao; Cui, Peng; Zhan, Kehui; Lin, Qiang; Zhuo, Guoyin; Guo, Xiaoli; Ding, Feng; Yang, Wenlong; Liu, Dongcheng; Hu, Songnian; Yu, Jun; Zhang, Aimin

2011-03-29

Plant mitochondria, semiautonomous organelles that function as manufacturers of cellular ATP, have their own genome that has a slow rate of evolution and rapid rearrangement. Cytoplasmic male sterility (CMS), a common phenotype in higher plants, is closely associated with rearrangements in mitochondrial DNA (mtDNA), and is widely used to produce F1 hybrid seeds in a variety of valuable crop species. Novel chimeric genes deduced from mtDNA rearrangements causing CMS have been identified in several plants, such as rice, sunflower, pepper, and rapeseed, but there are very few reports about mtDNA rearrangements in wheat. In the present work, we describe the mitochondrial genome of a wheat K-type CMS line and compare it with its maintainer line. The complete mtDNA sequence of a wheat K-type (with cytoplasm of Aegilops kotschyi) CMS line, Ks3, was assembled into a master circle (MC) molecule of 647,559 bp and found to harbor 34 known protein-coding genes, three rRNAs (18 S, 26 S, and 5 S rRNAs), and 16 different tRNAs. Compared to our previously published sequence of a K-type maintainer line, Km3, we detected Ks3-specific mtDNA (> 100 bp, 11.38%) and repeats (> 100 bp, 29 units) as well as genes that are unique to each line: rpl5 was missing in Ks3 and trnH was absent from Km3. We also defined 32 single nucleotide polymorphisms (SNPs) in 13 protein-coding, albeit functionally irrelevant, genes, and predicted 22 unique ORFs in Ks3, representing potential candidates for K-type CMS. All these sequence variations are candidates for involvement in CMS. A comparative analysis of the mtDNA of several angiosperms, including those from Ks3, Km3, rice, maize, Arabidopsis thaliana, and rapeseed, showed that non-coding sequences of higher plants had mostly divergent multiple reorganizations during the mtDNA evolution of higher plants. The complete mitochondrial genome of the wheat K-type CMS line Ks3 is very different from that of its maintainer line Km3, especially in non-coding sequences. Sequence rearrangement has produced novel chimeric ORFs, which may be candidate genes for CMS. Comparative analysis of several angiosperm mtDNAs indicated that non-coding sequences are the most frequently reorganized during mtDNA evolution in higher plants.

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.

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.

Comparative transcript profiling of the fertile and sterile flower buds of pol CMS in B. napus.

PubMed

An, Hong; Yang, Zonghui; Yi, Bin; Wen, Jing; Shen, Jinxiong; Tu, Jinxing; Ma, Chaozhi; Fu, Tingdong

2014-04-03

The Polima (pol) system of cytoplasmic male sterility (CMS) and its fertility restoration gene Rfp have been used in hybrid breeding in Brassica napus, which has greatly improved the yield of rapeseed. However, the mechanism of the male sterility transition in pol CMS remains to be determined. To investigate the transcriptome during the male sterility transition in pol CMS, a near-isogenic line (NIL) of pol CMS was constructed. The phenotypic features and sterility stage were confirmed by anatomical analysis. Subsequently, we compared the genomic expression profiles of fertile and sterile young flower buds by RNA-Seq. A total of 105,481,136 sequences were successfully obtained. These reads were assembled into 112,770 unigenes, which composed the transcriptome of the bud. Among these unigenes, 72,408 (64.21%) were annotated using public protein databases and classified into functional clusters. In addition, we investigated the changes in expression of the fertile and sterile buds; the RNA-seq data showed 1,148 unigenes had significantly different expression and they were mainly distributed in metabolic and protein synthesis pathways. Additionally, some unigenes controlling anther development were dramatically down-regulated in sterile buds. These results suggested that an energy deficiency caused by orf224/atp6 may inhibit a series of genes that regulate pollen development through nuclear-mitochondrial interaction. This results in the sterility of pol CMS by leading to the failure of sporogenous cell differentiation. This study may provide assistance for detailed molecular analysis and a better understanding of pol CMS in B. napus.

Implementation of NASTRAN on the IBM/370 CMS operating system

NASA Technical Reports Server (NTRS)

Britten, S. S.; Schumacker, B.

1980-01-01

The NASA Structural Analysis (NASTRAN) computer program is operational on the IBM 360/370 series computers. While execution of NASTRAN has been described and implemented under the virtual storage operating systems of the IBM 370 models, the IBM 370/168 computer can also operate in a time-sharing mode under the virtual machine operating system using the Conversational Monitor System (CMS) subset. The changes required to make NASTRAN operational under the CMS operating system are described.

CMS Analysis and Data Reduction with Apache Spark

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

Gutsche, Oliver; Canali, Luca; Cremer, Illia

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

Passage Key Inlet, Florida; CMS Modeling and Borrow Site Impact Analysis

DTIC Science & Technology

2016-06-01

Impact Analysis by Kelly R. Legault and Sirisha Rayaprolu PURPOSE: This Coastal and Hydraulics Engineering Technical Note (CHETN) describes the...use of a nested Coastal Modeling System (CMS) model for Passage Key Inlet, which is one of the connections between the Gulf of Mexico and Tampa Bay...driven sediment transport at Passage Key Inlet. This analysis resulted in issuing a new Florida Department of Environmental Protection (FDEP) permit to

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.

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.

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

Collagen Membranes Adsorb the Transforming Growth Factor-β Receptor I Kinase-Dependent Activity of Enamel Matrix Derivative.

PubMed

Stähli, Alexandra; Miron, Richard J; Bosshardt, Dieter D; Sculean, Anton; Gruber, Reinhard

2016-05-01

Enamel matrix derivative (EMD) and collagen membranes (CMs) are simultaneously applied in regenerative periodontal surgery. The aim of this study is to evaluate the ability of two CMs and a collagen matrix to adsorb the activity intrinsic to EMD that provokes transforming growth factor (TGF)-β signaling in oral fibroblasts. Three commercially available collagen products were exposed to EMD or recombinant TGF-β1, followed by vigorous washing. Oral fibroblasts were either seeded directly onto collagen products or were incubated with the respective supernatant. Expression of TGF-β target genes interleukin (IL)-11 and proteoglycan 4 (PRG4) was evaluated by real time polymerase chain reaction. Proteomic analysis was used to study the fraction of EMD proteins binding to collagen. EMD or TGF-β1 provoked a significant increase of IL-11 and PRG4 expression of oral fibroblasts when seeded onto collagen products and when incubated with the respective supernatant. Gene expression was blocked by the TGF-β receptor I kinase inhibitor SB431542. Amelogenin bound most abundantly to gelatin-coated culture dishes. However, incubation of palatal fibroblasts with recombinant amelogenin did not alter expression of IL-11 and PRG4. These in vitro findings suggest that collagen products adsorb a TGF-β receptor I kinase-dependent activity of EMD and make it available for potential target cells.

Identification of Proteins Involved in Carbohydrate Metabolism and Energy Metabolism Pathways and Their Regulation of Cytoplasmic Male Sterility in Wheat.

PubMed

Geng, Xingxia; Ye, Jiali; Yang, Xuetong; Li, Sha; Zhang, Lingli; Song, Xiyue

2018-01-23

Cytoplasmic male sterility (CMS) where no functional pollen is produced has important roles in wheat breeding. The anther is a unique organ for male gametogenesis and its abnormal development can cause male sterility. However, the mechanisms and regulatory networks related to plant male sterility are poorly understood. In this study, we conducted comparative analyses using isobaric tags for relative and absolute quantification (iTRAQ) of the pollen proteins in a CMS line and its wheat maintainer. Differentially abundant proteins (DAPs) were analyzed based on Gene Ontology classifications, metabolic pathways and transcriptional regulation networks using Blast2GO. We identified 5570 proteins based on 23,277 peptides, which matched with 73,688 spectra, including proteins in key pathways such as glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase and 6-phosphofructokinase 1 in the glycolysis pathway, isocitrate dehydrogenase and citrate synthase in the tricarboxylic acid cycle and nicotinamide adenine dinucleotide (NADH)-dehydrogenase and adenosine-triphosphate (ATP) synthases in the oxidative phosphorylation pathway. These proteins may comprise a network that regulates male sterility in wheat. Quantitative real time polymerase chain reaction (qRT-PCR) analysis, ATP assays and total sugar assays validated the iTRAQ results. These DAPs could be associated with abnormal pollen grain formation and male sterility. Our findings provide insights into the molecular mechanism related to male sterility in wheat.

Comparative studies of mitochondrial proteomics reveal an intimate protein network of male sterility in wheat (Triticum aestivum L.)

PubMed Central

Wang, Shuping; Zhang, Gaisheng; Zhang, Yingxin; Song, Qilu; Chen, Zheng; Wang, Junsheng; Guo, Jialin; Niu, Na; Wang, Junwei; Ma, Shoucai

2015-01-01

Plant male sterility has often been associated with mitochondrial dysfunction; however, the mechanism in wheat (Triticum aestivum L.) has not been elucidated. This study set out to probe the mechanism of physiological male sterility (PHYMS) induced by the chemical hybridizing agent (CHA)-SQ-1, and cytoplasmic male sterility (CMS) of wheat at the proteomic level. A total of 71 differentially expressed mitochondrial proteins were found to be involved in pollen abortion and further identified by MALDI-TOF/TOF MS (matrix-assisted laser desorption/ionization-time of fight/time of flight mass spectrometry). These proteins were implicated in different cellular responses and metabolic processes, with obvious functional tendencies toward the tricarboxylic acid cycle, the mitochondrial electron transport chain, protein synthesis and degradation, oxidation stress, the cell division cycle, and epigenetics. Interactions between identified proteins were demonstrated by bioinformatics analysis, enabling a more complete insight into biological pathways involved in anther abortion and pollen defects. Accordingly, a mitochondria-mediated male sterility protein network in wheat is proposed; this network was further confirmed by physiological data, RT-PCR (real-time PCR), and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling) assay. The results provide intriguing insights into the metabolic pathway of anther abortion induced by CHA-SQ-1 and also give useful clues to identify the crucial proteins of PHYMS and CMS in wheat. PMID:26136264

Transduction of Wnt11 promotes mesenchymal stem cell transdifferentiation into cardiac phenotypes.

PubMed

He, Zhisong; Li, Hongxia; Zuo, Shi; Pasha, Zeeshan; Wang, Yigang; Yang, Yueting; Jiang, Wenping; Ashraf, Muhammad; Xu, Meifeng

2011-10-01

Transplantation of mesenchymal stem cells (MSCs) has emerged as a potential treatment for ischemic heart repair. Previous studies have suggested that Wnt11 plays a critical role in cardiac specification and morphogenesis. In this study, we examined whether transduction of Wnt11 directly increases MSC differentiation into cardiac phenotypes. MSCs harvested from rat bone marrow were transduced with both Wnt11 and green fluorescent protein (GFP) (MSC(Wnt11)) using the murine stem cell virus (pMSCV) retroviral expression system; control cells were only GFP-transfected (MSC(Null)). Compared with control cells, MSC(Wnt11) was shown to have higher expression of Wnt11 by immunofluorescence, real-time polymerase chain reaction, and western blotting. MSC(Wnt11) shows a higher expression of cardiac-specific genes, including GATA-4, brain natriuretic peptide (BNP), islet-1, and α-actinin, after being cultured with cardiomyocytes (CMs) isolated from ventricles of neonatal (1-3 day) SD rats. Some MSC(Wnt11) were positive for α-actinin when MSCs were cocultured with native CMs for 7 days. Electron microscopy further confirmed the appearance of sarcomeres in MSC(Wnt11). Connexin 43 was found between GFP-positive MSCs and neonatal rat CMs labeled with red fluorescent probe PKH26. The transdifferentiation rate was significantly higher in MSC(Wnt11) than in MSC(Null), as assessed by flow cytometry. Functional studies indicated that the differentiation of MSC(Wnt11) was diminished by knockdown of GATA-4 with GATA-4-siRNA. Transduction of Wnt11 into MSCs increases their differentiation into CMs by upregulating GATA-4.

A gLite FTS based solution for managing user output in CMS

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

Cinquilli, M.; Riahi, H.; Spiga, D.

2012-01-01

The CMS distributed data analysis workflow assumes that jobs run in a different location from where their results are finally stored. Typically the user output must be transferred across the network from one site to another, possibly on a different continent or over links not necessarily validated for high bandwidth/high reliability transfer. This step is named stage-out and in CMS was originally implemented as a synchronous step of the analysis job execution. However, our experience showed the weakness of this approach both in terms of low total job execution efficiency and failure rates, wasting precious CPU resources. The nature ofmore » analysis data makes it inappropriate to use PhEDEx, the core data placement system for CMS. As part of the new generation of CMS Workload Management tools, the Asynchronous Stage-Out system (AsyncStageOut) has been developed to enable third party copy of the user output. The AsyncStageOut component manages glite FTS transfers of data from the temporary store at the site where the job ran to the final location of the data on behalf of that data owner. The tool uses python daemons, built using the WMCore framework, and CouchDB, to manage the queue of work and FTS transfers. CouchDB also provides the platform for a dedicated operations monitoring system. In this paper, we present the motivations of the asynchronous stage-out system. We give an insight into the design and the implementation of key features, describing how it is coupled with the CMS workload management system. Finally, we show the results and the commissioning experience.« less

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.

The microwell control of embryoid body size in order to regulate cardiac differentiation of human embryonic stem cells.

PubMed

Mohr, Jeffrey C; Zhang, Jianhua; Azarin, Samira M; Soerens, Andrew G; de Pablo, Juan J; Thomson, James A; Lyons, Gary E; Palecek, Sean P; Kamp, Timothy J

2010-03-01

The differentiation of human embryonic stem cells (hESCs) into cardiomyocytes (CMs) using embryoid bodies (EBs) is relatively inefficient and highly variable. Formation of EBs using standard enzymatic disaggregation techniques results in a wide range of sizes and geometries of EBs. Use of a 3-D cuboidal microwell system to culture hESCs in colonies of defined dimensions, 100-500 microm in lateral dimensions and 120 microm in depth, enabled formation of more uniform-sized EBs. The 300 microm microwells produced highest percentage of contracting EBs, but flow cytometry for myosin light chain 2A (MLC2a) expressing cells revealed a similar percentage (approximately 3%) of cardiomyocytes formed in EBs from 100 microm to 300 microm microwells. These data, and immunolabeling with anti-MF20 and MLC2a, suggest that the smaller EBs are less likely to form contracting EBs, but those contracting EBs are relatively enriched in cardiomyocytes compared to larger EB sizes where CMs make up a proportionately smaller fraction of the total cells. We conclude that microwell-engineered EB size regulates cardiogenesis and can be used for more efficient and reproducible formation of hESC-CMs needed for research and therapeutic applications. (c) 2009 Elsevier Ltd. All rights reserved.

Dynamic behavior of cellular materials and cellular structures: Experiments and modeling

NASA Astrophysics Data System (ADS)

Gao, Ziyang

Cellular solids, including cellular materials and cellular structures (CMS), have attracted people's great interests because of their low densities and novel physical, mechanical, thermal, electrical and acoustic properties. They offer potential for lightweight structures, energy absorption, thermal management, etc. Therefore, the studies of cellular solids have become one of the hottest research fields nowadays. From energy absorption point of view, any plastically deformed structures can be divided into two types (called type I and type II), and the basic cells of the CMS may take the configurations of these two types of structures. Accordingly, separated discussions are presented in this thesis. First, a modified 1-D model is proposed and numerically solved for a typical type II structure. Good agreement is achieved with the previous experimental data, hence is used to simulate the dynamic behavior of a type II chain. Resulted from different load speeds, interesting collapse modes are observed, and the parameters which govern the cell's post-collapse behavior are identified through a comprehensive non-dimensional analysis on general cellular chains. Secondly, the MHS specimens are chosen as an example of type I foam materials because of their good uniformity of the cell geometry. An extensive experimental study was carried out, where more attention was paid to their responses to dynamic loadings. Great enhancement of the stress-strain curve was observed in dynamic cases, and the energy absorption capacity is found to be several times higher than that of the commercial metal foams. Based on the experimental study, finite elemental simulations and theoretical modeling are also conducted, achieving good agreements and demonstrating the validities of those models. It is believed that the experimental, numerical and analytical results obtained in the present study will certainly deepen the understanding of the unsolved fundamental issues on the mechanical behavior of cellular solids and make substantial contributions to the theoretical advance of impact dynamics.

Differential proteomic analysis of the anti-depressive effects of oleamide in a rat chronic mild stress model of depression.

PubMed

Ge, Lin; Zhu, Ming-Ming; Yang, Jing-Yu; Wang, Fang; Zhang, Rong; Zhang, Jing-Hai; Shen, Jing; Tian, Hui-Fang; Wu, Chun-Fu

2015-04-01

Depression is a complex psychiatric disorder, and its etiology and pathophysiology are not completely understood. Depression involves changes in many biogenic amine, neuropeptide, and oxidative systems, as well as alterations in neuroendocrine function and immune-inflammatory pathways. Oleamide is a fatty amide which exhibits pharmacological effects leading to hypnosis, sedation, and anti-anxiety effects. In the present study, the chronic mild stress (CMS) model was used to investigate the antidepressant-like activity of oleamide. Rats were exposed to 10weeks of CMS or control conditions and were then subsequently treated with 2weeks of daily oleamide (5mg/kg, i.p.), fluoxetine (10mg/kg, i.p.), or vehicle. Protein extracts from the hippocampus were then collected, and hippocampal maps were generated by way of two-dimensional gel electrophoresis (2-DE). Altered proteins induced by CMS and oleamide were identified through mass spectrometry and database searches. Compared to the control group, the CMS rats exhibited significantly less body weight gain and decreased sucrose consumption. Treatment with oleamide caused a reversal of the CMS-induced deficit in sucrose consumption. In the proteomic analysis, 12 protein spots were selected and identified. CMS increased the levels of adenylate kinase isoenzyme 1 (AK1), nucleoside diphosphate kinase B (NDKB), histidine triad nucleotide-binding protein 1 (HINT1), acyl-protein thioesterase 2 (APT-2), and glutathione S-transferase A4 (GSTA4). Compared to the CMS samples, seven spots changed significantly following treatment with oleamide, including GSTA4, glutathione S-transferase A6 (GSTA6), GTP-binding nuclear protein Ran (Ran-GTP), ATP synthase subunit d, transgelin-3, small ubiquitin-related modifier 2 (SUMO2), and eukaryotic translation initiation factor 5A-1 (eIF5A1). Of these seven proteins, the level of eIF5A1 was up-regulated, whereas the remaining proteins were down-regulated. In conclusion, oleamide has antidepressant-like properties in the CMS rat model. The identification of proteins altered by CMS and oleamide treatment provides support for targeting these proteins in the development of novel therapies for depression. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Genome-wide comparative analysis of DNA methylation between soybean cytoplasmic male-sterile line NJCMS5A and its maintainer NJCMS5B.

PubMed

Li, Yanwei; Ding, Xianlong; Wang, Xuan; He, Tingting; Zhang, Hao; Yang, Longshu; Wang, Tanliu; Chen, Linfeng; Gai, Junyi; Yang, Shouping

2017-08-10

DNA methylation is an important epigenetic modification. It can regulate the expression of many key genes without changing the primary structure of the genomic DNA, and plays a vital role in the growth and development of the organism. The genome-wide DNA methylation profile of the cytoplasmic male sterile (CMS) line in soybean has not been reported so far. In this study, genome-wide comparative analysis of DNA methylation between soybean CMS line NJCMS5A and its maintainer NJCMS5B was conducted by whole-genome bisulfite sequencing. The results showed 3527 differentially methylated regions (DMRs) and 485 differentially methylated genes (DMGs), including 353 high-credible methylated genes, 56 methylated genes coding unknown protein and 76 novel methylated genes with no known function were identified. Among them, 25 DMRs were further validated that the genome-wide DNA methylation data were reliable through bisulfite treatment, and 9 DMRs were confirmed the relationship between DNA methylation and gene expression by qRT-PCR. Finally, 8 key DMGs possibly associated with soybean CMS were identified. Genome-wide DNA methylation profile of the soybean CMS line NJCMS5A and its maintainer NJCMS5B was obtained for the first time. Several specific DMGs which participated in pollen and flower development were further identified to be probably associated with soybean CMS. This study will contribute to further understanding of the molecular mechanism behind soybean CMS.

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.

76 FR 18555 - Statement of Organization, Functions, and Delegations of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-04

... leadership over the strategic planning process and the development of CMS strategic goals, metrics, and plans. Direct the development of financial and health care trend analysis and management insight report to inform senior CMS leadership strategic decision making. Set priorities for CSP direction, budget...

42 CFR 410.142 - CMS process for approving national accreditation organizations.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... (5) A description of the organization's data management and analysis system for its accreditation... organizations. 410.142 Section 410.142 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... Diabetes Self-Management Training and Diabetes Outcome Measurements § 410.142 CMS process for approving...

42 CFR 410.142 - CMS process for approving national accreditation organizations.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... (5) A description of the organization's data management and analysis system for its accreditation... organizations. 410.142 Section 410.142 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... Diabetes Self-Management Training and Diabetes Outcome Measurements § 410.142 CMS process for approving...

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.

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

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.

Differential proteomics analysis to identify proteins and pathways associated with male sterility of soybean using iTRAQ-based strategy.

PubMed

Li, Jiajia; Ding, Xianlong; Han, Shaohuai; He, Tingting; Zhang, Hao; Yang, Longshu; Yang, Shouping; Gai, Junyi

2016-04-14

To further elucidate the molecular mechanism of cytoplasmic male sterility (CMS) in soybean, a differential proteomic analysis was completed between the CMS line NJCMS1A and its maintainer NJCMS1B using iTRAQ-based strategy. As a result, 180 differential abundance proteins (DAPs) were identified, of which, 60 were down-regulated and 120 were up-regulated in NJCMS1A compared with NJCMS1B. Bioinformatic analysis showed that 167 DAPs were annotated in 41 Gene Ontology functional groups, 106 DAPs were classified into 20 clusters of orthologous groups of protein categories, and 128 DAPs were enrichment in 53 KEGG pathways. Fifteen differential level proteins/genes with the same expression pattern were identified in the further conjoint analysis of DAPs and the previously reported differential expression genes. Moreover, multiple reaction monitoring test, qRT-PCR analysis and enzyme activity assay validated that the iTRAQ results were reliable. Based on functional analysis of DAPs, we concluded that male sterility in NJCMS1A might be related to insufficiencies in energy supply, unbalance of protein synthesis and degradation, disruption of flavonoid synthesis, programmed cell death, abnormalities of substance metabolism, etc. These results might facilitate our understanding of the molecular mechanisms behind CMS in soybean. Soybean is an important global crop that provides protein and oil. Heterosis is a significantly potential approach to increase the yield of soybean. Cytoplasmic male sterility (CMS) plays a vital role in the production of hybrid seeds. However, the genetic and molecular mechanisms of male sterility in soybean still need to be further elucidated. In the present paper, a differential proteomic analysis was carried out and the results showed that several key proteins involved in key pathways were associated with male sterility in soybean. This work provides a new insight to understand the genetic and molecular mechanisms underlying CMS in soybean. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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.

RooStatsCms: A tool for analysis modelling, combination and statistical studies

NASA Astrophysics Data System (ADS)

Piparo, D.; Schott, G.; Quast, G.

2010-04-01

RooStatsCms is an object oriented statistical framework based on the RooFit technology. Its scope is to allow the modelling, statistical analysis and combination of multiple search channels for new phenomena in High Energy Physics. It provides a variety of methods described in literature implemented as classes, whose design is oriented to the execution of multiple CPU intensive jobs on batch systems or on the Grid.

Evolution of the pilot infrastructure of CMS: towards a single glideinWMS pool

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

Belforte, S.; Gutsche, O.; Letts, J.

2014-01-01

CMS production and analysis job submission is based largely on glideinWMS and pilot submissions. The transition from multiple different submission solutions like gLite WMS and HTCondor-based implementations was carried out over years and is coming now to a conclusion. The historically explained separate glideinWMS pools for different types of production jobs and analysis jobs are being unified into a single global pool. This enables CMS to benefit from global prioritization and scheduling possibilities. It also presents the sites with only one kind of pilots and eliminates the need of having to make scheduling decisions on the CE level. This papermore » provides an analysis of the benefits of a unified resource pool, as well as a description of the resulting global policy. It will explain the technical challenges moving forward and present solutions to some of them.« less

Current Status of the Congenital Myasthenic Syndromes

PubMed Central

Engel, Andrew G.

2011-01-01

Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. Clinical, electrophysiologic, and morphologic studies have paved the way for detecting CMS-related mutations in proteins residing in the nerve terminal, the synaptic basal lamina, and in the postsynaptic region of the motor endplate. The disease proteins identified to date include choline acetyltransferase (ChAT), the endplate species of acetylcholinesterase (AChE), β2-laminin, the acetylcholine receptor (AChR), rapsyn, plectin, Nav1.4, the muscle specific protein kinase (MuSK), agrin, downstream of tyrosine kinase 7 (Dok-7), and glutamine-fructose-6-phosphate transaminase 1 (GFPT1). Myasthenic syndromes associated with centronuclear myopathies were recently recognized. Analysis of properties of expressed mutant proteins contributed to finding improved therapy for most CMS. Despite these advances, the molecular basis of some phenotypically characterized CMS remains elusive. Moreover, other types of CMS and disease genes likely exist and await discovery. PMID:22104196

The CMS High Level Trigger System: Experience and Future Development

NASA Astrophysics Data System (ADS)

Bauer, G.; Behrens, U.; Bowen, M.; Branson, J.; Bukowiec, S.; Cittolin, S.; Coarasa, J. A.; Deldicque, C.; Dobson, M.; Dupont, A.; Erhan, S.; Flossdorf, A.; Gigi, D.; Glege, F.; Gomez-Reino, R.; Hartl, C.; Hegeman, J.; Holzner, A.; Hwong, Y. L.; Masetti, L.; Meijers, F.; Meschi, E.; Mommsen, R. K.; O'Dell, V.; Orsini, L.; Paus, C.; Petrucci, A.; Pieri, M.; Polese, G.; Racz, A.; Raginel, O.; Sakulin, H.; Sani, M.; Schwick, C.; Shpakov, D.; Simon, S.; Spataru, A. C.; Sumorok, K.

2012-12-01

The CMS experiment at the LHC features a two-level trigger system. Events accepted by the first level trigger, at a maximum rate of 100 kHz, are read out by the Data Acquisition system (DAQ), and subsequently assembled in memory in a farm of computers running a software high-level trigger (HLT), which selects interesting events for offline storage and analysis at a rate of order few hundred Hz. The HLT algorithms consist of sequences of offline-style reconstruction and filtering modules, executed on a farm of 0(10000) CPU cores built from commodity hardware. Experience from the operation of the HLT system in the collider run 2010/2011 is reported. The current architecture of the CMS HLT, its integration with the CMS reconstruction framework and the CMS DAQ, are discussed in the light of future development. The possible short- and medium-term evolution of the HLT software infrastructure to support extensions of the HLT computing power, and to address remaining performance and maintenance issues, are discussed.

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.

Electrophysiological characteristics of embryonic stem cell-derived cardiomyocytes are cell line-dependent.

PubMed

Hannes, Tobias; Wolff, Marie; Doss, Michael Xavier; Pfannkuche, Kurt; Haustein, Moritz; Müller-Ehmsen, Jochen; Sachinidis, Agapios; Hescheler, Jürgen; Khalil, Markus; Halbach, Marcel

2015-01-01

Modelling of cardiac development, physiology and pharmacology by differentiation of embryonic stem cells (ESCs) requires comparability of cardiac differentiation between different ESC lines. To investigate whether the outcome of cardiac differentiation is consistent between different ESC lines, we compared electrophysiological properties of ESC-derived cardiomyocytes (ESC-CMs) of different murine ESC lines. Two wild-type (D3 and R1) and two transgenic ESC lines (D3/aPIG44 and CGR8/AMPIGX-7) were differentiated under identical culture conditions. The transgenic cell lines expressed enhanced green fluorescent protein (eGFP) and puromycin-N-acetyltransferase under control of the cardiac specific α-myosin heavy chain (αMHC) promoter. Action potentials (APs) were recorded using sharp electrodes and multielectrode arrays in beating clusters of ESC-CMs. Spontaneous AP frequency and AP duration (APD) as well as maximal upstroke velocity differed markedly between unpurified CMs of the four ESC lines. APD heterogeneity was negligible in D3/aPIG44, moderate in D3 and R1 and extensive in CGR8/AMPIGX-7. Interspike intervals calculated from long-term recordings showed a high degree of variability within and between recordings in CGR8/AMPIGX-7, but not in D3/aPIG44. Purification of the αMHC+ population by puromycin treatment posed only minor changes to APD in D3/aPIG44, but significantly shortened APD in CGR8/AMPIGX-7. Electrophysiological properties of ESC-CMs are strongly cell line-dependent and can be influenced by purification of cardiomyocytes by antibiotic selection. Thus, conclusions on cardiac development, physiology and pharmacology derived from single stem cell lines have to be interpreted carefully. © 2015 S. Karger AG, Basel.

Bringing the CMS distributed computing system into scalable operations

NASA Astrophysics Data System (ADS)

Belforte, S.; Fanfani, A.; Fisk, I.; Flix, J.; Hernández, J. M.; Kress, T.; Letts, J.; Magini, N.; Miccio, V.; Sciabà, A.

2010-04-01

Establishing efficient and scalable operations of the CMS distributed computing system critically relies on the proper integration, commissioning and scale testing of the data and workload management tools, the various computing workflows and the underlying computing infrastructure, located at more than 50 computing centres worldwide and interconnected by the Worldwide LHC Computing Grid. Computing challenges periodically undertaken by CMS in the past years with increasing scale and complexity have revealed the need for a sustained effort on computing integration and commissioning activities. The Processing and Data Access (PADA) Task Force was established at the beginning of 2008 within the CMS Computing Program with the mandate of validating the infrastructure for organized processing and user analysis including the sites and the workload and data management tools, validating the distributed production system by performing functionality, reliability and scale tests, helping sites to commission, configure and optimize the networking and storage through scale testing data transfers and data processing, and improving the efficiency of accessing data across the CMS computing system from global transfers to local access. This contribution reports on the tools and procedures developed by CMS for computing commissioning and scale testing as well as the improvements accomplished towards efficient, reliable and scalable computing operations. The activities include the development and operation of load generators for job submission and data transfers with the aim of stressing the experiment and Grid data management and workload management systems, site commissioning procedures and tools to monitor and improve site availability and reliability, as well as activities targeted to the commissioning of the distributed production, user analysis and monitoring systems.

Genetic Variation in SENP1 and ANP32D as Predictors of Chronic Mountain Sickness

PubMed Central

Petousi, Nayia; Cavalleri, Gianpiero L.; Robbins, Peter A.

2014-01-01

Abstract Cole, Amy M., Nayia Petousi, Gianpiero L. Cavalleri, and Peter A. Robbins Genetic variation in SENP1 and ANP32D as predictors of chronic mountain sickness. High Alt Med Biol 15:497–499, 2014.—Chronic mountain sickness (CMS) is a serious illness that affects life-long high-altitude residents. A recent study analyzed whole genome sequence data from residents of Cerro de Pasco (Peru) in an effort to identify the genetic basis of CMS and reported SENP1 (rs7963934) and ANP32D (rs72644851) to show signatures consistent with natural selection and protective against CMS (Zhou et al. 2013). We set out to replicate these observations in two Andean cohorts from Cerro de Pasco, consisting of 84 CMS cases and 91 healthy controls in total. We report evidence of association for rs7963934 (SENP1) in the combined cohorts (meta-analysis p=8.8 x 10−4 OR 2.91, CI 1.56–5.5, I=0). The direction of effect was the same as in the original publication. We did not observe any significant correlation between rs72644851 (ANP32D) and the CMS phenotype, within or across cohorts (meta-analysis p=0.204, OR 1.37, CI 0.84–2.241, I=0). Our results provide independent evidence in support of a role for SENP1 in CMS in individuals of Quechua ancestry and suggest the SENP1 and ANP32D signatures of selection are in tight linkage disequilibrium (LD). PMID:25225945

Influence of the cortical midline structures on moral emotion and motivation in moral decision-making.

PubMed

Han, Hyemin; Chen, Jingyuan; Jeong, Changwoo; Glover, Gary H

2016-04-01

The present study aims to examine the relationship between the cortical midline structures (CMS), which have been regarded to be associated with selfhood, and moral decision making processes at the neural level. Traditional moral psychological studies have suggested the role of moral self as the moderator of moral cognition, so activity of moral self would present at the neural level. The present study examined the interaction between the CMS and other moral-related regions by conducting psycho-physiological interaction analysis of functional images acquired while 16 subjects were solving moral dilemmas. Furthermore, we performed Granger causality analysis to demonstrate the direction of influences between activities in the regions in moral decision-making. We first demonstrate there are significant positive interactions between two central CMS seed regions-i.e., the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC)-and brain regions associated with moral functioning including the cerebellum, brainstem, midbrain, dorsolateral prefrontal cortex, orbitofrontal cortex and anterior insula (AI); on the other hand, the posterior insula (PI) showed significant negative interaction with the seed regions. Second, several significant Granger causality was found from CMS to insula regions particularly under the moral-personal condition. Furthermore, significant dominant influence from the AI to PI was reported. Moral psychological implications of these findings are discussed. The present study demonstrated the significant interaction and influence between the CMS and morality-related regions while subject were solving moral dilemmas. Given that, activity in the CMS is significantly involved in human moral functioning. Copyright © 2016 Elsevier B.V. All rights reserved.

CMS distributed data analysis with CRAB3

NASA Astrophysics Data System (ADS)

Mascheroni, M.; Balcas, J.; Belforte, S.; Bockelman, B. P.; Hernandez, J. M.; Ciangottini, D.; Konstantinov, P. B.; Silva, J. M. D.; Ali, M. A. B. M.; Melo, A. M.; Riahi, H.; Tanasijczuk, A. J.; Yusli, M. N. B.; Wolf, M.; Woodard, A. E.; Vaandering, E.

2015-12-01

The CMS Remote Analysis Builder (CRAB) is a distributed workflow management tool which facilitates analysis tasks by isolating users from the technical details of the Grid infrastructure. Throughout LHC Run 1, CRAB has been successfully employed by an average of 350 distinct users each week executing about 200,000 jobs per day. CRAB has been significantly upgraded in order to face the new challenges posed by LHC Run 2. Components of the new system include 1) a lightweight client, 2) a central primary server which communicates with the clients through a REST interface, 3) secondary servers which manage user analysis tasks and submit jobs to the CMS resource provisioning system, and 4) a central service to asynchronously move user data from temporary storage in the execution site to the desired storage location. The new system improves the robustness, scalability and sustainability of the service. Here we provide an overview of the new system, operation, and user support, report on its current status, and identify lessons learned from the commissioning phase and production roll-out.

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.

Enhanced Predictability Through Lagrangian Observations and Analysis

DTIC Science & Technology

2008-09-30

Analysis PI: B. L. Lipphardt, Jr. University of Delaware, Robinson Hall, Newark, DE 19716 phone: (302) 831-6836 fax: (302) 831-6521 email: brucel ...udel.edu Award Number: N0014-05-1-0092 http://laplace.cms.udel.edu/~ brucel /lwad07 LONG-TERM GOALS Our long-term goal is better understanding of...laplace.cms.udel.edu/~ brucel /lwad07 for example products for 17 October 2007. Twenty-four hour mean forecast near-surface currents and relative dispersion

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

Sirunyan, A. M.; Tumasyan, A.; Adam, W.

A measurement of the cross section for top quark-antiquark (tt¯) pairs produced in association with a photon in proton-proton collisions at √s = 8 TeV is presented. The analysis uses data collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 19.7 fb 1. The signal is defined as the production of a tt¯ pair in association with a photon having a transverse energy larger than 25 GeV and an absolute pseudorapidity smaller than 1.44. The measurement is performed in the fiducial phase space corresponding to the semileptonic decay chain of the tt¯ pair, and themore » cross section is measured relative to the inclusive tt¯ pair production cross section. The fiducial cross section for associated tt¯ pair and photon production is found to be 127 ±27 (stat+syst) fb per semileptonic final state. In conclusion, the measured value is in agreement with the theoretical prediction.« less

Measurement of masses in the toverline{t} system by kinematic endpoints in pp collisions at √{s}=7 TeV

NASA Astrophysics Data System (ADS)

Chatrchyan, S.; Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Bergauer, T.; Dragicevic, M.; Erö, J.; Fabjan, C.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hörmann, N.; Hrubec, J.; Jeitler, M.; Kiesenhofer, W.; Knünz, V.; Krammer, M.; Krätschmer, I.; Liko, D.; Mikulec, I.; Rabady, D.; Rahbaran, B.; Rohringer, C.; Rohringer, H.; Schöfbeck, R.; Strauss, J.; Taurok, A.; Treberer-Treberspurg, W.; Waltenberger, W.; Wulz, C.-E.; Mossolov, V.; Shumeiko, N.; Suarez Gonzalez, J.; Alderweireldt, S.; Bansal, M.; Bansal, S.; Cornelis, T.; De Wolf, E. A.; Janssen, X.; Knutsson, A.; Luyckx, S.; Mucibello, L.; Ochesanu, S.; Roland, B.; Rougny, R.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Blekman, F.; Blyweert, S.; D'Hondt, J.; Kalogeropoulos, A.; Keaveney, J.; Maes, M.; Olbrechts, A.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Onsem, G. P.; Villella, I.; Clerbaux, B.; De Lentdecker, G.; Gay, A. P. R.; Hreus, T.; Léonard, A.; Marage, P. E.; Mohammadi, A.; Reis, T.; Thomas, L.; Vander Velde, C.; Vanlaer, P.; Wang, J.; Adler, V.; Beernaert, K.; Benucci, L.; Cimmino, A.; Costantini, S.; Dildick, S.; Garcia, G.; Klein, B.; Lellouch, J.; Marinov, A.; Mccartin, J.; Ocampo Rios, A. A.; Ryckbosch, D.; Sigamani, M.; Strobbe, N.; Thyssen, F.; Tytgat, M.; Walsh, S.; Yazgan, E.; Zaganidis, N.; Basegmez, S.; Bruno, G.; Castello, R.; Caudron, A.; Ceard, L.; Delaere, C.; du Pree, T.; Favart, D.; Forthomme, L.; Giammanco, A.; Hollar, J.; Lemaitre, V.; Liao, J.; Militaru, O.; Nuttens, C.; Pagano, D.; Pin, A.; Piotrzkowski, K.; Popov, A.; Selvaggi, M.; Vizan Garcia, J. M.; Beliy, N.; Caebergs, T.; Daubie, E.; Hammad, G. H.; Alves, G. A.; Correa Martins Junior, M.; Martins, T.; Pol, M. E.; Souza, M. H. G.; Aldá Júnior, W. L.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; De Jesus Damiao, D.; De Oliveira Martins, C.; Fonseca De Souza, S.; Malbouisson, H.; Malek, M.; Matos Figueiredo, D.; Mundim, L.; Nogima, H.; Prado Da Silva, W. L.; Santoro, A.; Soares Jorge, L.; Sznajder, A.; Tonelli Manganote, E. J.; Vilela Pereira, A.; Anjos, T. S.; Bernardes, C. A.; Dias, F. A.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Lagana, C.; Marinho, F.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Genchev, V.; Iaydjiev, P.; Piperov, S.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Tcholakov, V.; Trayanov, R.; Vutova, M.; Dimitrov, A.; Hadjiiska, R.; Kozhuharov, V.; Litov, L.; Pavlov, B.; Petkov, P.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Jiang, C. H.; Liang, D.; Liang, S.; Meng, X.; Tao, J.; Wang, J.; Wang, X.; Wang, Z.; Xiao, H.; Xu, M.; Asawatangtrakuldee, C.; Ban, Y.; Guo, Y.; Li, Q.; Li, W.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Zhang, L.; Zou, W.; Avila, C.; Carrillo Montoya, C. A.; Gomez, J. P.; Gomez Moreno, B.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Plestina, R.; Polic, D.; Puljak, I.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Duric, S.; Kadija, K.; Luetic, J.; Mekterovic, D.; Morovic, S.; Tikvica, L.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Finger, M.; Finger, M.; Assran, Y.; Ellithi Kamel, A.; Mahmoud, M. A.; Mahrous, A.; Radi, A.; Kadastik, M.; Müntel, M.; Murumaa, M.; Raidal, M.; Rebane, L.; Tiko, A.; Eerola, P.; Fedi, G.; Voutilainen, M.; Härkönen, J.; Karimäki, V.; Kinnunen, R.; Kortelainen, M. J.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Peltola, T.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Wendland, L.; Korpela, A.; Tuuva, T.; Besancon, M.; Choudhury, S.; Couderc, F.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. L.; Ferri, F.; Ganjour, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Locci, E.; Malcles, J.; Millischer, L.; Nayak, A.; Rander, J.; Rosowsky, A.; Titov, M.; Baffioni, S.; Beaudette, F.; Benhabib, L.; Bianchini, L.; Bluj, M.; Busson, P.; Charlot, C.; Daci, N.; Dahms, T.; Dalchenko, M.; Dobrzynski, L.; Florent, A.; Granier de Cassagnac, R.; Haguenauer, M.; Miné, P.; Mironov, C.; Naranjo, I. N.; Nguyen, M.; Ochando, C.; Paganini, P.; Sabes, D.; Salerno, R.; Sirois, Y.; Veelken, C.; Zabi, A.; Agram, J.-L.; Andrea, J.; Bloch, D.; Bodin, D.; Brom, J.-M.; Chabert, E. C.; Collard, C.; Conte, E.; Drouhin, F.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Goetzmann, C.; Juillot, P.; Le Bihan, A.-C.; Van Hove, P.; Beauceron, S.; Beaupere, N.; Boudoul, G.; Brochet, S.; Chasserat, J.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Fay, J.; Gascon, S.; Gouzevitch, M.; Ille, B.; Kurca, T.; Lethuillier, M.; Mirabito, L.; Perries, S.; Sgandurra, L.; Sordini, V.; Tschudi, Y.; Vander Donckt, M.; Verdier, P.; Viret, S.; Tsamalaidze, Z.; Autermann, C.; Beranek, S.; Calpas, B.; Edelhoff, M.; Feld, L.; Heracleous, N.; Hindrichs, O.; Klein, K.; Merz, J.; Ostapchuk, A.; Perieanu, A.; Raupach, F.; Sammet, J.; Schael, S.; Sprenger, D.; Weber, H.; Wittmer, B.; Zhukov, V.; Ata, M.; Caudron, J.; Dietz-Laursonn, E.; Duchardt, D.; Erdmann, M.; Fischer, R.; Güth, A.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Klingebiel, D.; Kreuzer, P.; Merschmeyer, M.; Meyer, A.; Olschewski, M.; Padeken, K.; Papacz, P.; Pieta, H.; Reithler, H.; Schmitz, S. A.; Sonnenschein, L.; Steggemann, J.; Teyssier, D.; Thüer, S.; Weber, M.; Cherepanov, V.; Erdogan, Y.; Flügge, G.; Geenen, H.; Geisler, M.; Haj Ahmad, W.; Hoehle, F.; Kargoll, B.; Kress, T.; Kuessel, Y.; Lingemann, J.; Nowack, A.; Nugent, I. M.; Perchalla, L.; Pooth, O.; Stahl, A.; Aldaya Martin, M.; Asin, I.; Bartosik, N.; Behr, J.; Behrenhoff, W.; Behrens, U.; Bergholz, M.; Bethani, A.; Borras, K.; Burgmeier, A.; Cakir, A.; Calligaris, L.; Campbell, A.; Costanza, F.; Dammann, D.; Diez Pardos, C.; Dorland, T.; Eckerlin, G.; Eckstein, D.; Flucke, G.; Geiser, A.; Glushkov, I.; Gunnellini, P.; Habib, S.; Hauk, J.; Hellwig, G.; Jung, H.; Kasemann, M.; Katsas, P.; Kleinwort, C.; Kluge, H.; Krämer, M.; Krücker, D.; Kuznetsova, E.; Lange, W.; Leonard, J.; Lipka, K.; Lohmann, W.; Lutz, B.; Mankel, R.; Marfin, I.; Marienfeld, M.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mnich, J.; Mussgiller, A.; Naumann-Emme, S.; Novgorodova, O.; Nowak, F.; Olzem, J.; Perrey, H.; Petrukhin, A.; Pitzl, D.; Raspereza, A.; Ribeiro Cipriano, P. M.; Riedl, C.; Ron, E.; Rosin, M.; Salfeld-Nebgen, J.; Schmidt, R.; Schoerner-Sadenius, T.; Sen, N.; Stein, M.; Walsh, R.; Wissing, C.; Blobel, V.; Enderle, H.; Erfle, J.; Gebbert, U.; Görner, M.; Gosselink, M.; Haller, J.; Heine, K.; Höing, R. S.; Kaussen, G.; Kirschenmann, H.; Klanner, R.; Lange, J.; Peiffer, T.; Pietsch, N.; Rathjens, D.; Sander, C.; Schettler, H.; Schleper, P.; Schlieckau, E.; Schmidt, A.; Schröder, M.; Schum, T.; Seidel, M.; Sibille, J.; Sola, V.; Stadie, H.; Steinbrück, G.; Thomsen, J.; Vanelderen, L.; Barth, C.; Baus, C.; Berger, J.; Böser, C.; Chwalek, T.; De Boer, W.; Descroix, A.; Dierlamm, A.; Feindt, M.; Guthoff, M.; Hackstein, C.; Hartmann, F.; Hauth, T.; Heinrich, M.; Held, H.; Hoffmann, K. H.; Husemann, U.; Katkov, I.; Komaragiri, J. R.; Kornmayer, A.; Lobelle Pardo, P.; Martschei, D.; Mueller, S.; Müller, Th.; Niegel, M.; Nürnberg, A.; Oberst, O.; Ott, J.; Quast, G.; Rabbertz, K.; Ratnikov, F.; Ratnikova, N.; Röcker, S.; Schilling, F.-P.; Schott, G.; Simonis, H. J.; Stober, F. M.; Troendle, D.; Ulrich, R.; Wagner-Kuhr, J.; Wayand, S.; Weiler, T.; Zeise, M.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Kesisoglou, S.; Kyriakis, A.; Loukas, D.; Markou, A.; Markou, C.; Ntomari, E.; Gouskos, L.; Mertzimekis, T. J.; Panagiotou, A.; Saoulidou, N.; Stiliaris, E.; Aslanoglou, X.; Evangelou, I.; Flouris, G.; Foudas, C.; Kokkas, P.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Bencze, G.; Hajdu, C.; Hidas, P.; Horvath, D.; Radics, B.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. J.; Beni, N.; Czellar, S.; Molnar, J.; Palinkas, J.; Szillasi, Z.; Karancsi, J.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Beri, S. B.; Bhatnagar, V.; Dhingra, N.; Gupta, R.; Kaur, M.; Mehta, M. Z.; Mittal, M.; Nishu, N.; Saini, L. K.; Sharma, A.; Singh, J. B.; Kumar, Ashok; Kumar, Arun; Ahuja, S.; Bhardwaj, A.; Choudhary, B. C.; Malhotra, S.; Naimuddin, M.; Ranjan, K.; Saxena, P.; Sharma, V.; Shivpuri, R. K.; Banerjee, S.; Bhattacharya, S.; Chatterjee, K.; Dutta, S.; Gomber, B.; Jain, Sa.; Jain, Sh.; Khurana, R.; Modak, A.; Mukherjee, S.; Roy, D.; Sarkar, S.; Sharan, M.; Abdulsalam, A.; Dutta, D.; Kailas, S.; Kumar, V.; Mohanty, A. K.; Pant, L. M.; Shukla, P.; Topkar, A.; Aziz, T.; Chatterjee, R. M.; Ganguly, S.; Guchait, M.; Gurtu, A.; Maity, M.; Majumder, G.; Mazumdar, K.; Mohanty, G. B.; Parida, B.; Sudhakar, K.; Wickramage, N.; Banerjee, S.; Dugad, S.; Arfaei, H.; Bakhshiansohi, H.; Etesami, S. M.; Fahim, A.; Hesari, H.; Jafari, A.; Khakzad, M.; Mohammadi Najafabadi, M.; Paktinat Mehdiabadi, S.; Safarzadeh, B.; Zeinali, M.; Grunewald, M.; Abbrescia, M.; Barbone, L.; Calabria, C.; Chhibra, S. S.; Colaleo, A.; Creanza, D.; De Filippis, N.; De Palma, M.; Fiore, L.; Iaselli, G.; Maggi, G.; Maggi, M.; Marangelli, B.; My, S.; Nuzzo, S.; Pacifico, N.; Pompili, A.; Pugliese, G.; Selvaggi, G.; Silvestris, L.; Singh, G.; Venditti, R.; Verwilligen, P.; Zito, G.; Abbiendi, G.; Benvenuti, A. C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Brigliadori, L.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Grandi, C.; Guiducci, L.; Marcellini, S.; Masetti, G.; Meneghelli, M.; Montanari, A.; Navarria, F. L.; Odorici, F.; Perrotta, A.; Primavera, F.; Rossi, A. M.; Rovelli, T.; Siroli, G. P.; Tosi, N.; Travaglini, R.; Albergo, S.; Chiorboli, M.; Costa, S.; Potenza, R.; Tricomi, A.; Tuve, C.; Barbagli, G.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Frosali, S.; Gallo, E.; Gonzi, S.; Lenzi, P.; Meschini, M.; Paoletti, S.; Sguazzoni, G.; Tropiano, A.; Benussi, L.; Bianco, S.; Fabbri, F.; Piccolo, D.; Fabbricatore, P.; Musenich, R.; Tosi, S.; Benaglia, A.; De Guio, F.; Di Matteo, L.; Fiorendi, S.; Gennai, S.; Ghezzi, A.; Govoni, P.; Lucchini, M. T.; Malvezzi, S.; Manzoni, R. A.; Martelli, A.; Massironi, A.; Menasce, D.; Moroni, L.; Paganoni, M.; Pedrini, D.; Ragazzi, S.; Redaelli, N.; Tabarelli de Fatis, T.; Buontempo, S.; Cavallo, N.; De Cosa, A.; Fabozzi, F.; Iorio, A. O. M.; Lista, L.; Meola, S.; Merola, M.; Paolucci, P.; Azzi, P.; Bacchetta, N.; Bellan, P.; Bisello, D.; Branca, A.; Carlin, R.; Checchia, P.; Dorigo, T.; Galanti, M.; Gasparini, F.; Gasparini, U.; Giubilato, P.; Gozzelino, A.; Kanishchev, K.; Lacaprara, S.; Lazzizzera, I.; Margoni, M.; Meneguzzo, A. T.; Michelotto, M.; Montecassiano, F.; Nespolo, M.; Pazzini, J.; Pegoraro, M.; Pozzobon, N.; Ronchese, P.; Simonetto, F.; Torassa, E.; Tosi, M.; Zotto, P.; Zumerle, G.; Gabusi, M.; Ratti, S. P.; Riccardi, C.; Vitulo, P.; Biasini, M.; Bilei, G. M.; Fanò, L.; Lariccia, P.; Mantovani, G.; Menichelli, M.; Nappi, A.; Romeo, F.; Saha, A.; Santocchia, A.; Spiezia, A.; Androsov, K.; Azzurri, P.; Bagliesi, G.; Boccali, T.; Broccolo, G.; Castaldi, R.; D'Agnolo, R. T.; Dell'Orso, R.; Fiori, F.; Foà, L.; Giassi, A.; Kraan, A.; Ligabue, F.; Lomtadze, T.; Martini, L.; Messineo, A.; Palla, F.; Rizzi, A.; Serban, A. T.; Spagnolo, P.; Squillacioti, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Vernieri, C.; Barone, L.; Cavallari, F.; Del Re, D.; Diemoz, M.; Fanelli, C.; Grassi, M.; Longo, E.; Margaroli, F.; Meridiani, P.; Micheli, F.; Nourbakhsh, S.; Organtini, G.; Paramatti, R.; Rahatlou, S.; Soffi, L.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Biino, C.; Cartiglia, N.; Casasso, S.; Costa, M.; De Remigis, P.; Demaria, N.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Musich, M.; Obertino, M. M.; Pastrone, N.; Pelliccioni, M.; Potenza, A.; Romero, A.; Ruspa, M.; Sacchi, R.; Solano, A.; Staiano, A.; Tamponi, U.; Belforte, S.; Candelise, V.; Casarsa, M.; Cossutti, F.; Della Ricca, G.; Gobbo, B.; La Licata, C.; Marone, M.; Montanino, D.; Penzo, A.; Schizzi, A.; Zanetti, A.; Kim, T. Y.; Nam, S. K.; Chang, S.; Kim, D. H.; Kim, G. N.; Kim, J. E.; Kong, D. J.; Oh, Y. D.; Park, H.; Son, D. C.; Kim, J. Y.; Kim, Zero J.; Song, S.; Choi, S.; Gyun, D.; Hong, B.; Jo, M.; Kim, H.; Kim, T. J.; Lee, K. S.; Moon, D. H.; Park, S. K.; Roh, Y.; Choi, M.; Kim, J. H.; Park, C.; Park, I. C.; Park, S.; Ryu, G.; Choi, Y.; Choi, Y. K.; Goh, J.; Kim, M. S.; Kwon, E.; Lee, B.; Lee, J.; Lee, S.; Seo, H.; Yu, I.; Grigelionis, I.; Juodagalvis, A.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Heredia-de La Cruz, I.; Lopez-Fernandez, R.; Martínez-Ortega, J.; Sanchez-Hernandez, A.; Villasenor-Cendejas, L. M.; Carrillo Moreno, S.; Vazquez Valencia, F.; Salazar Ibarguen, H. A.; Casimiro Linares, E.; Morelos Pineda, A.; Reyes-Santos, M. A.; Krofcheck, D.; Bell, A. J.; Butler, P. H.; Doesburg, R.; Reucroft, S.; Silverwood, H.; Ahmad, M.; Asghar, M. I.; Butt, J.; Hoorani, H. R.; Khalid, S.; Khan, W. A.; Khurshid, T.; Qazi, S.; Shah, M. A.; Shoaib, M.; Bialkowska, H.; Boimska, B.; Frueboes, T.; Górski, M.; Kazana, M.; Nawrocki, K.; Romanowska-Rybinska, K.; Szleper, M.; Wrochna, G.; Zalewski, P.; Brona, G.; Bunkowski, K.; Cwiok, M.; Dominik, W.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Misiura, M.; Wolszczak, W.; Almeida, N.; Bargassa, P.; David, A.; Faccioli, P.; Ferreira Parracho, P. G.; Gallinaro, M.; Seixas, J.; Varela, J.; Vischia, P.; Bunin, P.; Gavrilenko, M.; Golutvin, I.; Gorbunov, I.; Kamenev, A.; Karjavin, V.; Konoplyanikov, V.; Kozlov, G.; Lanev, A.; Malakhov, A.; Moisenz, P.; Palichik, V.; Perelygin, V.; Shmatov, S.; Smirnov, V.; Volodko, A.; Zarubin, A.; Evstyukhin, S.; Golovtsov, V.; Ivanov, Y.; Kim, V.; Levchenko, P.; Murzin, V.; Oreshkin, V.; Smirnov, I.; Sulimov, V.; Uvarov, L.; Vavilov, S.; Vorobyev, A.; Vorobyev, An.; Andreev, Yu.; Dermenev, A.; Gninenko, S.; Golubev, N.; Kirsanov, M.; Krasnikov, N.; Matveev, V.; Pashenkov, A.; Tlisov, D.; Toropin, A.; Epshteyn, V.; Erofeeva, M.; Gavrilov, V.; Lychkovskaya, N.; Popov, V.; Safronov, G.; Semenov, S.; Spiridonov, A.; Stolin, V.; Vlasov, E.; Zhokin, A.; Andreev, V.; Azarkin, M.; Dremin, I.; Kirakosyan, M.; Leonidov, A.; Mesyats, G.; Rusakov, S. V.; Vinogradov, A.; Belyaev, A.; Boos, E.; Bunichev, V.; Dubinin, M.; Dudko, L.; Ershov, A.; Gribushin, A.; Klyukhin, V.; Lokhtin, I.; Markina, A.; Obraztsov, S.; Perfilov, M.; Savrin, V.; Tsirova, N.; Azhgirey, I.; Bayshev, I.; Bitioukov, S.; Kachanov, V.; Kalinin, A.; Konstantinov, D.; Krychkine, V.; Petrov, V.; Ryutin, R.; Sobol, A.; Tourtchanovitch, L.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Adzic, P.; Ekmedzic, M.; Krpic, D.; Milosevic, J.; Aguilar-Benitez, M.; Alcaraz Maestre, J.; Battilana, C.; Calvo, E.; Cerrada, M.; Chamizo Llatas, M.; Colino, N.; De La Cruz, B.; Delgado Peris, A.; Domínguez Vázquez, D.; Fernandez Bedoya, C.; Fernández Ramos, J. P.; Ferrando, A.; Flix, J.; Fouz, M. C.; Garcia-Abia, P.; Gonzalez Lopez, O.; Goy Lopez, S.; Hernandez, J. M.; Josa, M. I.; Merino, G.; Navarro De Martino, E.; Puerta Pelayo, J.; Quintario Olmeda, A.; Redondo, I.; Romero, L.; Santaolalla, J.; Soares, M. S.; Willmott, C.; Albajar, C.; de Trocóniz, J. F.; Brun, H.; Cuevas, J.; Fernandez Menendez, J.; Folgueras, S.; Gonzalez Caballero, I.; Lloret Iglesias, L.; Piedra Gomez, J.; Brochero Cifuentes, J. A.; Cabrillo, I. J.; Calderon, A.; Chuang, S. H.; Duarte Campderros, J.; Fernandez, M.; Gomez, G.; Gonzalez Sanchez, J.; Graziano, A.; Jorda, C.; Lopez Virto, A.; Marco, J.; Marco, R.; Martinez Rivero, C.; Matorras, F.; Munoz Sanchez, F. J.; Rodrigo, T.; Rodríguez-Marrero, A. Y.; Ruiz-Jimeno, A.; Scodellaro, L.; Vila, I.; Vilar Cortabitarte, R.; Abbaneo, D.; Auffray, E.; Auzinger, G.; Bachtis, M.; Baillon, P.; Ball, A. H.; Barney, D.; Bendavid, J.; Benitez, J. F.; Bernet, C.; Bianchi, G.; Bloch, P.; Bocci, A.; Bonato, A.; Bondu, O.; Botta, C.; Breuker, H.; Camporesi, T.; Cerminara, G.; Christiansen, T.; Coarasa Perez, J. A.; Colafranceschi, S.; d'Enterria, D.; Dabrowski, A.; De Roeck, A.; De Visscher, S.; Di Guida, S.; Dobson, M.; Dupont-Sagorin, N.; Elliott-Peisert, A.; Eugster, J.; Funk, W.; Georgiou, G.; Giffels, M.; Gigi, D.; Gill, K.; Giordano, D.; Girone, M.; Giunta, M.; Glege, F.; Gomez-Reino Garrido, R.; Gowdy, S.; Guida, R.; Hammer, J.; Hansen, M.; Harris, P.; Hartl, C.; Hegner, B.; Hinzmann, A.; Innocente, V.; Janot, P.; Kaadze, K.; Karavakis, E.; Kousouris, K.; Krajczar, K.; Lecoq, P.; Lee, Y.-J.; Lourenço, C.; Magini, N.; Malberti, M.; Malgeri, L.; Mannelli, M.; Masetti, L.; Meijers, F.; Mersi, S.; Meschi, E.; Moser, R.; Mulders, M.; Musella, P.; Nesvold, E.; Orsini, L.; Palencia Cortezon, E.; Perez, E.; Perrozzi, L.; Petrilli, A.; Pfeiffer, A.; Pierini, M.; Pimiä, M.; Piparo, D.; Polese, G.; Quertenmont, L.; Racz, A.; Reece, W.; Rodrigues Antunes, J.; Rolandi, G.; Rovelli, C.; Rovere, M.; Sakulin, H.; Santanastasio, F.; Schäfer, C.; Schwick, C.; Segoni, I.; Sekmen, S.; Sharma, A.; Siegrist, P.; Silva, P.; Simon, M.; Sphicas, P.; Spiga, D.; Stoye, M.; Tsirou, A.; Veres, G. I.; Vlimant, J. R.; Wöhri, H. K.; Worm, S. D.; Zeuner, W. D.; Bertl, W.; Deiters, K.; Erdmann, W.; Gabathuler, K.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; König, S.; Kotlinski, D.; Langenegger, U.; Meier, F.; Renker, D.; Rohe, T.; Bachmair, F.; Bäni, L.; Bortignon, P.; Buchmann, M. A.; Casal, B.; Chanon, N.; Deisher, A.; Dissertori, G.; Dittmar, M.; Donegà, M.; Dünser, M.; Eller, P.; Grab, C.; Hits, D.; Lecomte, P.; Lustermann, W.; Marini, A. C.; Martinez Ruiz del Arbol, P.; Mohr, N.; Moortgat, F.; Nägeli, C.; Nef, P.; Nessi-Tedaldi, F.; Pandolfi, F.; Pape, L.; Pauss, F.; Peruzzi, M.; Ronga, F. J.; Rossini, M.; Sala, L.; Sanchez, A. K.; Starodumov, A.; Stieger, B.; Takahashi, M.; Tauscher, L.; Thea, A.; Theofilatos, K.; Treille, D.; Urscheler, C.; Wallny, R.; Weber, H. A.; Amsler, C.; Chiochia, V.; Favaro, C.; Ivova Rikova, M.; Kilminster, B.; Millan Mejias, B.; Otiougova, P.; Robmann, P.; Snoek, H.; Taroni, S.; Tupputi, S.; Verzetti, M.; Cardaci, M.; Chen, K. H.; Ferro, C.; Kuo, C. M.; Li, S. W.; Lin, W.; Lu, Y. J.; Volpe, R.; Yu, S. S.; Bartalini, P.; Chang, P.; Chang, Y. H.; Chang, Y. W.; Chao, Y.; Chen, K. F.; Dietz, C.; Grundler, U.; Hou, W.-S.; Hsiung, Y.; Kao, K. Y.; Lei, Y. J.; Lu, R.-S.; Majumder, D.; Petrakou, E.; Shi, X.; Shiu, J. G.; Tzeng, Y. M.; Wang, M.; Asavapibhop, B.; Suwonjandee, N.; Adiguzel, A.; Bakirci, M. N.; Cerci, S.; Dozen, C.; Dumanoglu, I.; Eskut, E.; Girgis, S.; Gokbulut, G.; Gurpinar, E.; Hos, I.; Kangal, E. E.; Kayis Topaksu, A.; Onengut, G.; Ozdemir, K.; Ozturk, S.; Polatoz, A.; Sogut, K.; Sunar Cerci, D.; Tali, B.; Topakli, H.; Vergili, M.; Akin, I. V.; Aliev, T.; Bilin, B.; Bilmis, S.; Deniz, M.; Gamsizkan, H.; Guler, A. M.; Karapinar, G.; Ocalan, K.; Ozpineci, A.; Serin, M.; Sever, R.; Surat, U. E.; Yalvac, M.; Zeyrek, M.; Gülmez, E.; Isildak, B.; Kaya, M.; Kaya, O.; Ozkorucuklu, S.; Sonmez, N.; Bahtiyar, H.; Barlas, E.; Cankocak, K.; Günaydin, Y. O.; Vardarlı, F. I.; Yücel, M.; Levchuk, L.; Sorokin, P.; Brooke, J. J.; Clement, E.; Cussans, D.; Flacher, H.; Frazier, R.; Goldstein, J.; Grimes, M.; Heath, G. P.; Heath, H. F.; Kreczko, L.; Metson, S.; Newbold, D. M.; Nirunpong, K.; Poll, A.; Senkin, S.; Smith, V. J.; Williams, T.; Basso, L.; Bell, K. W.; Belyaev, A.; Brew, C.; Brown, R. M.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Jackson, J.; Olaiya, E.; Petyt, D.; Radburn-Smith, B. C.; Shepherd-Themistocleous, C. H.; Tomalin, I. R.; Womersley, W. J.; Bainbridge, R.; Buchmuller, O.; Burton, D.; Colling, D.; Cripps, N.; Cutajar, M.; Dauncey, P.; Davies, G.; Della Negra, M.; Ferguson, W.; Fulcher, J.; Futyan, D.; Gilbert, A.; Guneratne Bryer, A.; Hall, G.; Hatherell, Z.; Hays, J.; Iles, G.; Jarvis, M.; Karapostoli, G.; Kenzie, M.; Lane, R.; Lucas, R.; Lyons, L.; Magnan, A.-M.; Marrouche, J.; Mathias, B.; Nandi, R.; Nash, J.; Nikitenko, A.; Pela, J.; Pesaresi, M.; Petridis, K.; Pioppi, M.; Raymond, D. M.; Rogerson, S.; Rose, A.; Seez, C.; Sharp, P.; Sparrow, A.; Tapper, A.; Vazquez Acosta, M.; Virdee, T.; Wakefield, S.; Wardle, N.; Whyntie, T.; Chadwick, M.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Leggat, D.; Leslie, D.; Martin, W.; Reid, I. D.; Symonds, P.; Teodorescu, L.; Turner, M.; Dittmann, J.; Hatakeyama, K.; Kasmi, A.; Liu, H.; Scarborough, T.; Charaf, O.; Cooper, S. I.; Henderson, C.; Rumerio, P.; Avetisyan, A.; Bose, T.; Fantasia, C.; Heister, A.; Lawson, P.; Lazic, D.; Rohlf, J.; Sperka, D.; St. John, J.; Sulak, L.; Alimena, J.; Bhattacharya, S.; Christopher, G.; Cutts, D.; Demiragli, Z.; Ferapontov, A.; Garabedian, A.; Heintz, U.; Kukartsev, G.; Laird, E.; Landsberg, G.; Luk, M.; Narain, M.; Segala, M.; Sinthuprasith, T.; Speer, T.; Breedon, R.; Breto, G.; Calderon De La Barca Sanchez, M.; Chauhan, S.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Erbacher, R.; Gardner, M.; Houtz, R.; Ko, W.; Kopecky, A.; Lander, R.; Mall, O.; Miceli, T.; Nelson, R.; Pellett, D.; Ricci-Tam, F.; Rutherford, B.; Searle, M.; Smith, J.; Squires, M.; Tripathi, M.; Yohay, R.; Andreev, V.; Cline, D.; Cousins, R.; Erhan, S.; Everaerts, P.; Farrell, C.; Felcini, M.; Hauser, J.; Ignatenko, M.; Jarvis, C.; Rakness, G.; Schlein, P.; Traczyk, P.; Valuev, V.; Weber, M.; Babb, J.; Clare, R.; Dinardo, M. E.; Ellison, J.; Gary, J. W.; Giordano, F.; Hanson, G.; Liu, H.; Long, O. R.; Luthra, A.; Nguyen, H.; Paramesvaran, S.; Sturdy, J.; Sumowidagdo, S.; Wilken, R.; Wimpenny, S.; Andrews, W.; Branson, J. G.; Cerati, G. B.; Cittolin, S.; Evans, D.; Holzner, A.; Kelley, R.; Lebourgeois, M.; Letts, J.; Macneill, I.; Mangano, B.; Padhi, S.; Palmer, C.; Petrucciani, G.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Sudano, E.; Tadel, M.; Tu, Y.; Vartak, A.; Wasserbaech, S.; Würthwein, F.; Yagil, A.; Yoo, J.; Barge, D.; Bellan, R.; Campagnari, C.; D'Alfonso, M.; Danielson, T.; Dishaw, A.; Flowers, K.; Geffert, P.; George, C.; Golf, F.; Incandela, J.; Justus, C.; Kalavase, P.; Kovalskyi, D.; Krutelyov, V.; Lowette, S.; Magaña Villalba, R.; Mccoll, N.; Pavlunin, V.; Ribnik, J.; Richman, J.; Rossin, R.; Stuart, D.; To, W.; West, C.; Apresyan, A.; Bornheim, A.; Bunn, J.; Chen, Y.; Di Marco, E.; Duarte, J.; Kcira, D.; Ma, Y.; Mott, A.; Newman, H. B.; Rogan, C.; Spiropulu, M.; Timciuc, V.; Veverka, J.; Wilkinson, R.; Xie, S.; Yang, Y.; Zhu, R. Y.; Azzolini, V.; Calamba, A.; Carroll, R.; Ferguson, T.; Iiyama, Y.; Jang, D. W.; Liu, Y. F.; Paulini, M.; Russ, J.; Vogel, H.; Vorobiev, I.; Cumalat, J. P.; Drell, B. R.; Ford, W. T.; Gaz, A.; Luiggi Lopez, E.; Nauenberg, U.; Smith, J. G.; Stenson, K.; Ulmer, K. A.; Wagner, S. R.; Alexander, J.; Chatterjee, A.; Eggert, N.; Gibbons, L. K.; Hopkins, W.; Khukhunaishvili, A.; Kreis, B.; Mirman, N.; Nachman, B.; Nicolas Kaufman, G.; Patterson, J. R.; Ryd, A.; Salvati, E.; Sun, W.; Teo, W. D.; Thom, J.; Thompson, J.; Tucker, J.; Weng, Y.; Winstrom, L.; Wittich, P.; Winn, D.; Abdullin, S.; Albrow, M.; Anderson, J.; Apollinari, G.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Burkett, K.; Butler, J. N.; Chetluru, V.; Cheung, H. W. K.; Chlebana, F.; Cihangir, S.; Elvira, V. D.; Fisk, I.; Freeman, J.; Gao, Y.; Gottschalk, E.; Gray, L.; Green, D.; Gutsche, O.; Harris, R. M.; Hirschauer, J.; Hooberman, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kunori, S.; Kwan, S.; Linacre, J.; Lincoln, D.; Lipton, R.; Lykken, J.; Maeshima, K.; Marraffino, J. M.; Martinez Outschoorn, V. I.; Maruyama, S.; Mason, D.; McBride, P.; Mishra, K.; Mrenna, S.; Musienko, Y.; Newman-Holmes, C.; O'Dell, V.; Prokofyev, O.; Sexton-Kennedy, E.; Sharma, S.; Spalding, W. J.; Spiegel, L.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vidal, R.; Whitmore, J.; Wu, W.; Yang, F.; Yun, J. C.; Acosta, D.; Avery, P.; Bourilkov, D.; Chen, M.; Cheng, T.; Das, S.; De Gruttola, M.; Di Giovanni, G. P.; Dobur, D.; Drozdetskiy, A.; Field, R. D.; Fisher, M.; Fu, Y.; Furic, I. K.; Hugon, J.; Kim, B.; Konigsberg, J.; Korytov, A.; Kropivnitskaya, A.; Kypreos, T.; Low, J. F.; Matchev, K.; Milenovic, P.; Mitselmakher, G.; Muniz, L.; Remington, R.; Rinkevicius, A.; Skhirtladze, N.; Snowball, M.; Yelton, J.; Zakaria, M.; Gaultney, V.; Hewamanage, S.; Lebolo, L. M.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Adams, T.; Askew, A.; Bochenek, J.; Chen, J.; Diamond, B.; Gleyzer, S. V.; Haas, J.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Prosper, H.; Veeraraghavan, V.; Weinberg, M.; Baarmand, M. M.; Dorney, B.; Hohlmann, M.; Kalakhety, H.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Bazterra, V. E.; Betts, R. R.; Bucinskaite, I.; Callner, J.; Cavanaugh, R.; Evdokimov, O.; Gauthier, L.; Gerber, C. E.; Hofman, D. J.; Khalatyan, S.; Kurt, P.; Lacroix, F.; O'Brien, C.; Silkworth, C.; Strom, D.; Turner, P.; Varelas, N.; Akgun, U.; Albayrak, E. A.; Bilki, B.; Clarida, W.; Dilsiz, K.; Duru, F.; Griffiths, S.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Newsom, C. R.; Ogul, H.; Onel, Y.; Ozok, F.; Sen, S.; Tan, P.; Tiras, E.; Wetzel, J.; Yetkin, T.; Yi, K.; Barnett, B. A.; Blumenfeld, B.; Bolognesi, S.; Fehling, D.; Giurgiu, G.; Gritsan, A. V.; Hu, G.; Maksimovic, P.; Swartz, M.; Whitbeck, A.; Baringer, P.; Bean, A.; Benelli, G.; Kenny, R. P., III; Murray, M.; Noonan, D.; Sanders, S.; Stringer, R.; Wood, J. S.; Barfuss, A. F.; Chakaberia, I.; Ivanov, A.; Khalil, S.; Makouski, M.; Maravin, Y.; Shrestha, S.; Svintradze, I.; Gronberg, J.; Lange, D.; Rebassoo, F.; Wright, D.; Baden, A.; Calvert, B.; Eno, S. C.; Gomez, J. A.; Hadley, N. J.; Kellogg, R. G.; Kolberg, T.; Lu, Y.; Marionneau, M.; Mignerey, A. C.; Pedro, K.; Peterman, A.; Skuja, A.; Temple, J.; Tonjes, M. B.; Tonwar, S. C.; Apyan, A.; Bauer, G.; Busza, W.; Butz, E.; Cali, I. A.; Chan, M.; Dutta, V.; Gomez Ceballos, G.; Goncharov, M.; Kim, Y.; Klute, M.; Lai, Y. S.; Levin, A.; Luckey, P. D.; Ma, T.; Nahn, S.; Paus, C.; Ralph, D.; Roland, C.; Roland, G.; Stephans, G. S. F.; Stöckli, F.; Sumorok, K.; Sung, K.; Velicanu, D.; Wolf, R.; Wyslouch, B.; Yang, M.; Yilmaz, Y.; Yoon, A. S.; Zanetti, M.; Zhukova, V.; Dahmes, B.; De Benedetti, A.; Franzoni, G.; Gude, A.; Haupt, J.; Kao, S. C.; Klapoetke, K.; Kubota, Y.; Mans, J.; Pastika, N.; Rusack, R.; Sasseville, M.; Singovsky, A.; Tambe, N.; Turkewitz, J.; Cremaldi, L. M.; Kroeger, R.; Perera, L.; Rahmat, R.; Sanders, D. A.; Summers, D.; Avdeeva, E.; Bloom, K.; Bose, S.; Claes, D. R.; Dominguez, A.; Eads, M.; Gonzalez Suarez, R.; Keller, J.; Kravchenko, I.; Lazo-Flores, J.; Malik, S.; Snow, G. R.; Dolen, J.; Godshalk, A.; Iashvili, I.; Jain, S.; Kharchilava, A.; Kumar, A.; Rappoccio, S.; Wan, Z.; Alverson, G.; Barberis, E.; Baumgartel, D.; Chasco, M.; Haley, J.; Nash, D.; Orimoto, T.; Trocino, D.; Wood, D.; Zhang, J.; Anastassov, A.; Hahn, K. A.; Kubik, A.; Lusito, L.; Mucia, N.; Odell, N.; Pollack, B.; Pozdnyakov, A.; Schmitt, M.; Stoynev, S.; Velasco, M.; Won, S.; Berry, D.; Brinkerhoff, A.; Chan, K. M.; Hildreth, M.; Jessop, C.; Karmgard, D. J.; Kolb, J.; Lannon, K.; Luo, W.; Lynch, S.; Marinelli, N.; Morse, D. M.; Pearson, T.; Planer, M.; Ruchti, R.; Slaunwhite, J.; Valls, N.; Wayne, M.; Wolf, M.; Antonelli, L.; Bylsma, B.; Durkin, L. S.; Hill, C.; Hughes, R.; Kotov, K.; Ling, T. Y.; Puigh, D.; Rodenburg, M.; Smith, G.; Vuosalo, C.; Williams, G.; Winer, B. L.; Wolfe, H.; Berry, E.; Elmer, P.; Halyo, V.; Hebda, P.; Hegeman, J.; Hunt, A.; Jindal, P.; Koay, S. A.; Lopes Pegna, D.; Lujan, P.; Marlow, D.; Medvedeva, T.; Mooney, M.; Olsen, J.; Piroué, P.; Quan, X.; Raval, A.; Saka, H.; Stickland, D.; Tully, C.; Werner, J. S.; Zenz, S. C.; Zuranski, A.; Brownson, E.; Lopez, A.; Mendez, H.; Ramirez Vargas, J. E.; Alagoz, E.; Benedetti, D.; Bolla, G.; Bortoletto, D.; De Mattia, M.; Everett, A.; Hu, Z.; Jones, M.; Koybasi, O.; Kress, M.; Leonardo, N.; Maroussov, V.; Merkel, P.; Miller, D. H.; Neumeister, N.; Shipsey, I.; Silvers, D.; Svyatkovskiy, A.; Vidal Marono, M.; Yoo, H. D.; Zablocki, J.; Zheng, Y.; Guragain, S.; Parashar, N.; Adair, A.; Akgun, B.; Ecklund, K. M.; Geurts, F. J. M.; Li, W.; Padley, B. P.; Redjimi, R.; Roberts, J.; Zabel, J.; Betchart, B.; Bodek, A.; Covarelli, R.; de Barbaro, P.; Demina, R.; Eshaq, Y.; Ferbel, T.; Garcia-Bellido, A.; Goldenzweig, P.; Han, J.; Harel, A.; Miner, D. C.; Petrillo, G.; Vishnevskiy, D.; Zielinski, M.; Bhatti, A.; Ciesielski, R.; Demortier, L.; Goulianos, K.; Lungu, G.; Malik, S.; Mesropian, C.; Arora, S.; Barker, A.; Chou, J. P.; Contreras-Campana, C.; Contreras-Campana, E.; Duggan, D.; Ferencek, D.; Gershtein, Y.; Gray, R.; Halkiadakis, E.; Hidas, D.; Lath, A.; Panwalkar, S.; Park, M.; Patel, R.; Rekovic, V.; Robles, J.; Rose, K.; Salur, S.; Schnetzer, S.; Seitz, C.; Somalwar, S.; Stone, R.; Walker, M.; Cerizza, G.; Hollingsworth, M.; Spanier, S.; Yang, Z. C.; York, A.; Eusebi, R.; Flanagan, W.; Gilmore, J.; Kamon, T.; Khotilovich, V.; Montalvo, R.; Osipenkov, I.; Pakhotin, Y.; Perloff, A.; Roe, J.; Safonov, A.; Sakuma, T.; Suarez, I.; Tatarinov, A.; Toback, D.; Akchurin, N.; Damgov, J.; Dragoiu, C.; Dudero, P. R.; Jeong, C.; Kovitanggoon, K.; Lee, S. W.; Libeiro, T.; Volobouev, I.; Appelt, E.; Delannoy, A. G.; Greene, S.; Gurrola, A.; Johns, W.; Maguire, C.; Mao, Y.; Melo, A.; Sharma, M.; Sheldon, P.; Snook, B.; Tuo, S.; Velkovska, J.; Arenton, M. W.; Balazs, M.; Boutle, S.; Cox, B.; Francis, B.; Goodell, J.; Hirosky, R.; Ledovskoy, A.; Lin, C.; Neu, C.; Wood, J.; Gollapinni, S.; Harr, R.; Karchin, P. E.; Kottachchi Kankanamge Don, C.; Lamichhane, P.; Sakharov, A.; Anderson, M.; Belknap, D. A.; Borrello, L.; Carlsmith, D.; Cepeda, M.; Dasu, S.; Friis, E.; Grogg, K. S.; Grothe, M.; Hall-Wilton, R.; Herndon, M.; Hervé, A.; Klabbers, P.; Klukas, J.; Lanaro, A.; Lazaridis, C.; Loveless, R.; Mohapatra, A.; Mozer, M. U.; Ojalvo, I.; Pierro, G. A.; Ross, I.; Savin, A.; Smith, W. H.; Swanson, J.

2013-07-01

A simultaneous measurement of the top-quark, W-boson, and neutrino masses is reported for events selected in the dilepton final state from a data sample corresponding to an integrated luminosity of 5.0 fb-1 collected by the CMS experiment in pp collisions at . The analysis is based on endpoint determinations in kinematic distributions. When the neutrino and W-boson masses are constrained to their world-average values, a top-quark mass value of is obtained. When such constraints are not used, the three particle masses are obtained in a simultaneous fit. In this unconstrained mode the study serves as a test of mass determination methods that may be used in beyond standard model physics scenarios where several masses in a decay chain may be unknown and undetected particles lead to underconstrained kinematics.

Integration of end-user Cloud storage for CMS analysis

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

Riahi, Hassen; Aimar, Alberto; Ayllon, Alejandro Alvarez

End-user Cloud storage is increasing rapidly in popularity in research communities thanks to the collaboration capabilities it offers, namely synchronisation and sharing. CERN IT has implemented a model of such storage named, CERNBox, integrated with the CERN AuthN and AuthZ services. To exploit the use of the end-user Cloud storage for the distributed data analysis activity, the CMS experiment has started the integration of CERNBox as a Grid resource. This will allow CMS users to make use of their own storage in the Cloud for their analysis activities as well as to benefit from synchronisation and sharing capabilities to achievemore » results faster and more effectively. It will provide an integration model of Cloud storages in the Grid, which is implemented and commissioned over the world’s largest computing Grid infrastructure, Worldwide LHC Computing Grid (WLCG). In this paper, we present the integration strategy and infrastructure changes needed in order to transparently integrate end-user Cloud storage with the CMS distributed computing model. We describe the new challenges faced in data management between Grid and Cloud and how they were addressed, along with details of the support for Cloud storage recently introduced into the WLCG data movement middleware, FTS3. Finally, the commissioning experience of CERNBox for the distributed data analysis activity is also presented.« less

Integration of end-user Cloud storage for CMS analysis

DOE PAGES

Riahi, Hassen; Aimar, Alberto; Ayllon, Alejandro Alvarez; ...

2017-05-19

End-user Cloud storage is increasing rapidly in popularity in research communities thanks to the collaboration capabilities it offers, namely synchronisation and sharing. CERN IT has implemented a model of such storage named, CERNBox, integrated with the CERN AuthN and AuthZ services. To exploit the use of the end-user Cloud storage for the distributed data analysis activity, the CMS experiment has started the integration of CERNBox as a Grid resource. This will allow CMS users to make use of their own storage in the Cloud for their analysis activities as well as to benefit from synchronisation and sharing capabilities to achievemore » results faster and more effectively. It will provide an integration model of Cloud storages in the Grid, which is implemented and commissioned over the world’s largest computing Grid infrastructure, Worldwide LHC Computing Grid (WLCG). In this paper, we present the integration strategy and infrastructure changes needed in order to transparently integrate end-user Cloud storage with the CMS distributed computing model. We describe the new challenges faced in data management between Grid and Cloud and how they were addressed, along with details of the support for Cloud storage recently introduced into the WLCG data movement middleware, FTS3. Finally, the commissioning experience of CERNBox for the distributed data analysis activity is also presented.« less

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).

CMS Data Processing Workflows during an Extended Cosmic Ray Run

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

Not Available

2009-11-01

The CMS Collaboration conducted a month-long data taking exercise, the Cosmic Run At Four Tesla, during October-November 2008, with the goal of commissioning the experiment for extended operation. With all installed detector systems participating, CMS recorded 270 million cosmic ray events with the solenoid at a magnetic field strength of 3.8 T. This paper describes the data flow from the detector through the various online and offline computing systems, as well as the workflows used for recording the data, for aligning and calibrating the detector, and for analysis of the data.

Searches for Kaluza-Klein graviton excitations and microscopic black holes with the aid of the CMS detector at the LHC

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

Savina, M. V., E-mail: savina@cern.ch

2015-06-15

A survey of the results of the Compact Muon Solenoid (CMS) experiment that concern searches for massive Kaluza-Klein graviton excitations and microscopic black holes, quantum black holes, and string balls within models of low-energy multidimensional gravity is presented on behalf of the CMS Collaboration. The analysis in question is performed on the basis of a complete sample of data accumulated for proton-proton collisions at the c.m. energies of 7 and 8 TeV at the Large Hadron Collider (LHC) over the period spanning 2010 and 2012.

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.

Comparative studies of mitochondrial proteomics reveal an intimate protein network of male sterility in wheat (Triticum aestivum L.).

PubMed

Wang, Shuping; Zhang, Gaisheng; Zhang, Yingxin; Song, Qilu; Chen, Zheng; Wang, Junsheng; Guo, Jialin; Niu, Na; Wang, Junwei; Ma, Shoucai

2015-10-01

Plant male sterility has often been associated with mitochondrial dysfunction; however, the mechanism in wheat (Triticum aestivum L.) has not been elucidated. This study set out to probe the mechanism of physiological male sterility (PHYMS) induced by the chemical hybridizing agent (CHA)-SQ-1, and cytoplasmic male sterility (CMS) of wheat at the proteomic level. A total of 71 differentially expressed mitochondrial proteins were found to be involved in pollen abortion and further identified by MALDI-TOF/TOF MS (matrix-assisted laser desorption/ionization-time of fight/time of flight mass spectrometry). These proteins were implicated in different cellular responses and metabolic processes, with obvious functional tendencies toward the tricarboxylic acid cycle, the mitochondrial electron transport chain, protein synthesis and degradation, oxidation stress, the cell division cycle, and epigenetics. Interactions between identified proteins were demonstrated by bioinformatics analysis, enabling a more complete insight into biological pathways involved in anther abortion and pollen defects. Accordingly, a mitochondria-mediated male sterility protein network in wheat is proposed; this network was further confirmed by physiological data, RT-PCR (real-time PCR), and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling) assay. The results provide intriguing insights into the metabolic pathway of anther abortion induced by CHA-SQ-1 and also give useful clues to identify the crucial proteins of PHYMS and CMS in wheat. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

'Ogura'-based 'CMS' lines with different nuclear backgrounds of cabbage revealed substantial diversity at morphological and molecular levels.

PubMed

Parkash, Chander; Kumar, Sandeep; Singh, Rajender; Kumar, Ajay; Kumar, Satish; Dey, Shyam Sundar; Bhatia, Reeta; Kumar, Raj

2018-01-01

A comprehensive study on characterization and genetic diversity analysis was carried out in 16 'Ogura'-based 'CMS' lines of cabbage using 14 agro-morphological traits and 29 SSR markers. Agro-morphological characterization depicted considerable variations for different horticultural traits studied. The genotype, ZHA-2, performed better for most of the economically important quantitative traits. Further, gross head weight (0.76), head length (0.60) and head width (0.83) revealed significant positive correlation with net head weight. Dendrogram based on 10 quantitative traits exhibited considerable diversity among different CMS lines and principle component analysis (PCA) indicated that net and gross head weight, and head length and width are the main components of divergence between 16 CMS lines of cabbage. In molecular study, a total of 58 alleles were amplified by 29 SSR primers, averaging to 2.0 alleles in each locus. High mean values of Shannon's Information index (0.62), expected (0.45) and observed (0.32) heterozygosity and polymorphic information content (0.35) depicted substantial polymorphism. Dendrogram based on Jaccard's similarity coefficient constructed two major groups and eight sub-groups, which revealed substantial diversity among different CMS lines. In overall, based on agro-morphological and molecular studies genotype RRMA, ZHA-2 and RCA were found most divergent. Hence, they have immense potential in future breeding programs for the high-yielding hybrid development in cabbage.

Monitoring the CMS strip tracker readout system

NASA Astrophysics Data System (ADS)

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

2008-07-01

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

Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by gram-negative bacteria.

PubMed

Plachouras, D; Karvanen, M; Friberg, L E; Papadomichelakis, E; Antoniadou, A; Tsangaris, I; Karaiskos, I; Poulakou, G; Kontopidou, F; Armaganidis, A; Cars, O; Giamarellou, H

2009-08-01

Colistin is used to treat infections caused by multidrug-resistant gram-negative bacteria (MDR-GNB). It is administered intravenously in the form of colistin methanesulfonate (CMS), which is hydrolyzed in vivo to the active drug. However, pharmacokinetic data are limited. The aim of the present study was to characterize the pharmacokinetics of CMS and colistin in a population of critically ill patients. Patients receiving colistin for the treatment of infections caused by MDR-GNB were enrolled in the study; however, patients receiving a renal replacement therapy were excluded. CMS was administered at a dose of 3 million units (240 mg) every 8 h. Venous blood was collected immediately before and at multiple occasions after the first and the fourth infusions. Plasma CMS and colistin concentrations were determined by a novel liquid chromatography-tandem mass spectrometry method after a rapid precipitation step that avoids the significant degradation of CMS and colistin. Population pharmacokinetic analysis was performed with the NONMEM program. Eighteen patients (6 females; mean age, 63.6 years; mean creatinine clearance, 82.3 ml/min) were included in the study. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.046 h and 2.3 h, respectively. The clearance of CMS was 13.7 liters/h. For colistin, a one-compartment model was sufficient to describe the data, and the estimated half-life was 14.4 h. The predicted maximum concentrations of drug in plasma were 0.60 mg/liter and 2.3 mg/liter for the first dose and at steady state, respectively. Colistin displayed a half-life that was significantly long in relation to the dosing interval. The implications of these findings are that the plasma colistin concentrations are insufficient before steady state and raise the question of whether the administration of a loading dose would benefit critically ill patients.

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

NASA Astrophysics Data System (ADS)

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

2014-06-01

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

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

ERIC Educational Resources Information Center

Quellmalz, Edys S.; Shaha, Steven

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

77 FR 55479 - Medicare, Medicaid, and CHIP Programs: Research and Analysis on Impact of CMS Programs on the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-10

... System AGENCY: Centers for Medicare & Medicaid Services (CMS), HHS. ACTION: Notice of Single Source Award... care system through a single source award. The Indian Health Service (IHS), Tribes and Tribal... adoption and impact of these new authorities on the Indian health care system. Amount of the Award The...

Development of male sterile Eruca sativa carrying a Raphanus sativus/Brassica oleracea cybrid cytoplasm.

PubMed

Nothnagel, Thomas; Klocke, Evelyn; Schrader, Otto; Linke, Bettina; Budahn, Holger

2016-02-01

Alloplasmic male sterile breeding lines of Eruca sativa were developed by intergeneric hybridization with CMS- Brassica oleracea, followed by recurrent backcrosses and determination of the breeding value. Male sterile breeding lines of rocket salad (Eruca sativa) were developed by intergeneric hybridization with cytoplasmic male sterile (CMS) cauliflower (Brassica oleracea) followed by recurrent backcrosses. Five amphidiploid F1 plants (2n = 2x = 20, CE), achieved by manual crosses and embryo rescue, showed an intermediate habit. The plants were completely male sterile and lacked seed set after pollination with the Eruca parent. Allotetraploid F1-hybrid plants (4n = 4x = 40, CCEE) obtained after colchicine treatment were backcrossed six times with pollen of the Eruca parent to select alloplasmic diploid E. sativa lines. The hybrid status and the nucleo-cytoplasmic constellation were continuously controlled by RAPD and Southern analysis during subsequent backcrosses. The ploidy level was investigated by flow cytometry and chromosome analysis. Premeiotic (sporophytic) and postmeiotic (pollen abortive) defects during the anther development were observed in the alloplasmic E. sativus plants in comparison to the CMS-cauliflower donor. No further incompatibilities were noticed between the CMS-inducing cybrid cytoplasm and the E. sativa nuclear genome. The final alloplasmic E. sativa lines were diploid with 2n = 2x = 22 chromosomes and revealed complete male sterility and restored female fertility. Plant vigor and yield potential of the CMS-E. sativa BC5 lines were comparable to the parental E. sativus line. In conclusion, the employed cybrid-cytoplasm has been proven as a vital source of CMS for E. sativa. The developed lines are directly applicable for hybrid breeding of rocket salad.

Image-based evaluation of contraction-relaxation kinetics of human-induced pluripotent stem cell-derived cardiomyocytes: Correlation and complementarity with extracellular electrophysiology.

PubMed

Hayakawa, Tomohiro; Kunihiro, Takeshi; Ando, Tomoko; Kobayashi, Seiji; Matsui, Eriko; Yada, Hiroaki; Kanda, Yasunari; Kurokawa, Junko; Furukawa, Tetsushi

2014-12-01

In this study, we used high-speed video microscopy with motion vector analysis to investigate the contractile characteristics of hiPS-CM monolayer, in addition to further characterizing the motion with extracellular field potential (FP), traction force and the Ca(2+) transient. Results of our traction force microscopy demonstrated that the force development of hiPS-CMs correlated well with the cellular deformation detected by the video microscopy with motion vector analysis. In the presence of verapamil and isoproterenol, contractile motion of hiPS-CMs showed alteration in accordance with the changes in fluorescence peak of the Ca(2+) transient, i.e., upstroke, decay, amplitude and full-width at half-maximum. Simultaneously recorded hiPS-CM motion and FP showed that there was a linear correlation between changes in the motion and field potential duration in response to verapamil (30-150nM), isoproterenol (0.1-10μM) and E-4031 (10-50nM). In addition, tetrodotoxin (3-30μM)-induced delay of sodium current was corresponded with the delay of the contraction onset of hiPS-CMs. These results indicate that the electrophysiological and functional behaviors of hiPS-CMs are quantitatively reflected in the contractile motion detected by this image-based technique. In the presence of 100nM E-4031, the occurrence of early after-depolarization-like negative deflection in FP was also detected in the hiPS-CM motion as a characteristic two-step relaxation pattern. These findings offer insights into the interpretation of the motion kinetics of the hiPS-CMs, and are relevant for understanding electrical and mechanical relationship in hiPS-CMs. Copyright © 2014. Published by Elsevier Ltd.

Effects of Anti-Hypertensive Monotherapy with Either Calcium Channel Blocker or Angiotensin Receptor Blocker on Arterial Stiffness, Central Hemodynamics, and Ventriculo-Arterial Coupling in Uncomplicated Hypertension Patients

PubMed Central

Lin, Heng-Hsu; Wang, Chia-Sung; Lin, Jiunn-Lee; Hwang, Juey-Jen; Lin, Lian-Yu

2013-01-01

Objectives This study is designed to investigate the effects of anti-hypertensive monotherapy [either calcium channel blocker (CCB) or angiotensin receptor blocker (ARB)] on pulsatile hemodynamic parameters in patients with uncomplicated hypertension. Methods This is a longitudinal observational study. For simplicity, we included patients with uncomplicated hypertension who receivedmono anti-hypertensive therapy with ARB or CCB. Hemodynamic parameters including central arterial pressure (CAP), aortic characteristic impedance (Zc), augmentation index (AI), brachial-ankle pulse wave velocity (baPWV), heart-ankle pulse wave velocity (haPWV), cardiac ultrasonographic parameters and ventriculo-arterial (VA) coupling were measured before, 1 month and 3 months after treatment. Results A total of 74 subjects were included in our study for analysis from 2007-2008. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and central systolic arterial pressure (CSAP) were significantly reduced 1 and 3 months after initiation of therapy. Among the pulsatile hemodynamic parameters, only the baPWV was significantly reduced (from1537.78 ± 200.63 cm/s to 1460.06 ± 186.09 cm/s to 1456.53 ± 196.03 cm/s, p for trend = 0.016). The haPWV only decreased with borderline significance (from 1015.38 ± 124.26 cm/s to 978.88 ± 126.55 cm/s to 967.99 ± 103.37 cm/s, p for trend = 0.041). The other pulsatile hemodynamic parameters remained unchanged before and after therapy. Subgroup analysis (age above or below52 years) showed that the baPWVwas significantly reduced only in the younger group. Conclusions Among the pulsatile hemodynamic parameters, only the baPWV was effectively reduced by either CCB or ARB. The improvement of PWV was more evident in younger subjects. PMID:27122681

Evolution of CMS workload management towards multicore job support

NASA Astrophysics Data System (ADS)

Pérez-Calero Yzquierdo, A.; Hernández, J. M.; Khan, F. A.; Letts, J.; Majewski, K.; Rodrigues, A. M.; McCrea, A.; Vaandering, E.

2015-12-01

The successful exploitation of multicore processor architectures is a key element of the LHC distributed computing system in the coming era of the LHC Run 2. High-pileup complex-collision events represent a challenge for the traditional sequential programming in terms of memory and processing time budget. The CMS data production and processing framework is introducing the parallel execution of the reconstruction and simulation algorithms to overcome these limitations. CMS plans to execute multicore jobs while still supporting singlecore processing for other tasks difficult to parallelize, such as user analysis. The CMS strategy for job management thus aims at integrating single and multicore job scheduling across the Grid. This is accomplished by employing multicore pilots with internal dynamic partitioning of the allocated resources, capable of running payloads of various core counts simultaneously. An extensive test programme has been conducted to enable multicore scheduling with the various local batch systems available at CMS sites, with the focus on the Tier-0 and Tier-1s, responsible during 2015 of the prompt data reconstruction. Scale tests have been run to analyse the performance of this scheduling strategy and ensure an efficient use of the distributed resources. This paper presents the evolution of the CMS job management and resource provisioning systems in order to support this hybrid scheduling model, as well as its deployment and performance tests, which will enable CMS to transition to a multicore production model for the second LHC run.

Evolution of CMS Workload Management Towards Multicore Job Support

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

Perez-Calero Yzquierdo, A.; Hernández, J. M.; Khan, F. A.

The successful exploitation of multicore processor architectures is a key element of the LHC distributed computing system in the coming era of the LHC Run 2. High-pileup complex-collision events represent a challenge for the traditional sequential programming in terms of memory and processing time budget. The CMS data production and processing framework is introducing the parallel execution of the reconstruction and simulation algorithms to overcome these limitations. CMS plans to execute multicore jobs while still supporting singlecore processing for other tasks difficult to parallelize, such as user analysis. The CMS strategy for job management thus aims at integrating single andmore » multicore job scheduling across the Grid. This is accomplished by employing multicore pilots with internal dynamic partitioning of the allocated resources, capable of running payloads of various core counts simultaneously. An extensive test programme has been conducted to enable multicore scheduling with the various local batch systems available at CMS sites, with the focus on the Tier-0 and Tier-1s, responsible during 2015 of the prompt data reconstruction. Scale tests have been run to analyse the performance of this scheduling strategy and ensure an efficient use of the distributed resources. This paper presents the evolution of the CMS job management and resource provisioning systems in order to support this hybrid scheduling model, as well as its deployment and performance tests, which will enable CMS to transition to a multicore production model for the second LHC run.« less

Development of a novel Sinapis arvensis disomic addition line in Brassica napus containing the restorer gene for Nsa CMS and improved resistance to Sclerotinia sclerotiorum and pod shattering.

PubMed

Wei, Wenhui; Li, Yunchang; Wang, Lijun; Liu, Shengyi; Yan, Xiaohong; Mei, Desheng; Li, Yinde; Xu, Yusong; Peng, Pengfei; Hu, Qiong

2010-04-01

An allo-cytoplasmic male sterile line, which was developed through somatic hybridization between Brassica napus and Sinapis arvensis (thus designated as Nsa CMS line), possesses high potential for hybrid production of rapeseed. In order to select for restorer lines, fertile plants derived from the same somatic hybridization combination were self-pollinated and testcrossed with the parental Nsa CMS line for six generations. A novel disomic alien addition line, B. napus-S. arvensis, has been successfully developed. GISH analysis showed that it contains one pair of chromosomes from S. arvensis and 19 pairs from B. napus, and retains stable and regular mitotic and meiotic processes. The addition line displays very strong restoration ability to Nsa CMS line, high resistance to Sclerotinia sclerotiorum and a low incidence of pod shattering. Because the addition line shares these very important agricultural characters, it is a valuable restorer to Nsa CMS line, and is named NR1 here (Nsa restorer no. 1).

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.

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.

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.

Patient Care Staffing Levels and Facility Characteristics in U.S. Hemodialysis Facilities

PubMed Central

Yoder, Laura A. G.; Xin, Wenjun; Norris, Keith C.; Yan, Guofen

2013-01-01

Background Higher numbers of registered nurses per patient have been associated with improved patient outcomes in acute care facilities. Variation and associations of patient-care staffing levels and hemodialysis facility characteristics have not been previously examined. Study Design Cross-sectional study using Poisson regression to examine associations betwee patient-care staffing levels and hemodialysis facility characteristics. Setting & Participants 4,800 U.S. hemodialysis facilities in the 2009 CMS ESRD Annual Facility Survey (CMS-2744), USRDS. Predictors Facility characteristics, including profit status, freestanding status, chain affiliatio and geographic region, adjusted for facility size, capacity, functional type, and urbanicity. Outcomes Patient care staffing levels, including ratios of Registered Nurses (RN), Licensed Practical Nurses (LPN), Patient Care Technicians (PCT), composite staff (RN+LPN+PCT), Social Workers, and Dietitians to in-center hemodialysis patients. Results After adjusting for background facility characteristics, the ratios of RNs and LPNs to patients were 35% (p<0.001) and 42% (p<0.001) lower, but the PCT-to-patient ratio was 16% (p<0.001) higher in for-profit facilities than those in nonprofit facilities (Rate ratio, 0.65, 95%CI, 0.63–0.68; 0.58, 0.51–0.65; 1.16, 1.12–1.19; respectively). Regionally, compared to the Northeast, the adjusted RN-to-patient ratio was 14% (p< 0.001) lower in the Midwest, 25% (p< 0.001) lower in the South, and 18% (p< 0.001) lower in the West. Even after additional adjustments, the large for-profit chains had significantly lower RN and LPN ratios than the largest nonprofit chain, but a significantly higher PCT-to-patient ratio. The overall composite staffing levels were also lower in for-profit and chain-affiliated facilities. The patterns hold when the hospital-based units were excluded. Limitations Nursing hours were not available. Conclusions The significant variation in patient-care staffing levels and its associations with facility characteristics warrants inclusion in future large-scale hemodialysis outcomes studies. ESRD networks and hemodialysis facilities should attend to quality assurance and performance improvement initiatives that maximize licensed nurse-staffing levels in hemodialysis facilities. PMID:23810689

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.

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.

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.

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

CMS distributed data analysis with CRAB3

DOE PAGES

Mascheroni, M.; Balcas, J.; Belforte, S.; ...

2015-12-23

The CMS Remote Analysis Builder (CRAB) is a distributed workflow management tool which facilitates analysis tasks by isolating users from the technical details of the Grid infrastructure. Throughout LHC Run 1, CRAB has been successfully employed by an average of 350 distinct users each week executing about 200,000 jobs per day.CRAB has been significantly upgraded in order to face the new challenges posed by LHC Run 2. Components of the new system include 1) a lightweight client, 2) a central primary server which communicates with the clients through a REST interface, 3) secondary servers which manage user analysis tasks andmore » submit jobs to the CMS resource provisioning system, and 4) a central service to asynchronously move user data from temporary storage in the execution site to the desired storage location. Furthermore, the new system improves the robustness, scalability and sustainability of the service.Here we provide an overview of the new system, operation, and user support, report on its current status, and identify lessons learned from the commissioning phase and production roll-out.« less

CMS Use of a Data Federation

NASA Astrophysics Data System (ADS)

Bloom, Kenneth; Cms Collaboration

2014-06-01

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

Dataset definition for CMS operations and physics analyses

NASA Astrophysics Data System (ADS)

Franzoni, Giovanni; Compact Muon Solenoid Collaboration

2016-04-01

Data recorded at the CMS experiment are funnelled into streams, integrated in the HLT menu, and further organised in a hierarchical structure of primary datasets and secondary datasets/dedicated skims. Datasets are defined according to the final-state particles reconstructed by the high level trigger, the data format and the use case (physics analysis, alignment and calibration, performance studies). During the first LHC run, new workflows have been added to this canonical scheme, to exploit at best the flexibility of the CMS trigger and data acquisition systems. The concepts of data parking and data scouting have been introduced to extend the physics reach of CMS, offering the opportunity of defining physics triggers with extremely loose selections (e.g. dijet resonance trigger collecting data at a 1 kHz). In this presentation, we review the evolution of the dataset definition during the LHC run I, and we discuss the plans for the run II.

Genetic analysis and molecular mapping of an Rf gene from Helianthus angustifolius for a new cytoplasmic male-sterile line

USDA-ARS?s Scientific Manuscript database

The combination of cytoplasmic male-sterile (CMS) and the corresponding fertility restoration genes (Rf) is a critical tool in large-scale hybrid seed production of sunflower. A new CMS line 514A, derived from H. tuberosus / 7718B, was obtained from a scientific exchange with the Liaoning Academy of...

40 CFR Table 5 of Subpart Aaaaaaa... - Applicability of General Provisions to Subpart AAAAAAA

Code of Federal Regulations, 2010 CFR

2010-07-01

... must be conducted. § 63.7(e)(2)-(4) Conduct of Performance Tests and Data Reduction Yes. § 63.7(f)-(h) Use of Alternative Test Method; Data Analysis, Recordkeeping, and Reporting; and Waiver of Performance... CMS requirements. § 63.8(e)-(f) CMS Performance Evaluation Yes. § 63.8(g)(1)-(4) Data Reduction...

Synthesis and characterization of microporous inorganic membranes for propylene/propane separation

NASA Astrophysics Data System (ADS)

Ma, Xiaoli

Membrane-based gas separation is promising for efficient propylene/propane (C3H6/C3H8) separation with low energy consumption and minimum environment impact. Two microporous inorganic membrane candidates, MFI-type zeolite membrane and carbon molecular sieve membrane (CMS) have demonstrated excellent thermal and chemical stability. Application of these membranes into C3H6/C3H 8 separation has not been well investigated. This dissertation presents fundamental studies on membrane synthesis, characterization and C3H 6/C3H8 separation properties of MFI zeolite membrane and CMS membrane. MFI zeolite membranes were synthesized on α-alumina supports by secondary growth method. Novel positron annihilation spectroscopy (PAS) techniques were used to non-destructively characterize the pore structure of these membranes. PAS reveals a bimodal pore structure consisting of intracrystalline zeolitic micropores of ~0.6 nm in diameter and irregular intercrystalline micropores of 1.4 to 1.8 nm in size for the membranes. The template-free synthesized membrane exhibited a high permeance but a low selectivity in C3H 6/C3H8 mixture separation. CMS membranes were synthesized by coating/pyrolysis method on mesoporous gamma-alumina support. Such supports allow coating of thin, high-quality polymer films and subsequent CMS membranes with no infiltration into support pores. The CMS membranes show strong molecular sieving effect, offering a high C3H 6/C3H8 mixture selectivity of ~30. Reduction in membrane thickness from 500 nm to 300 nm causes an increase in C3H8 permeance and He/N2 selectivity, but a decrease in the permeance of He, N 2 and C3H6 and C3H6/C 3H8 selectivity. This can be explained by the thickness dependent chain mobility of the polymer film resulting in final carbon membrane of reduced pore size with different effects on transport of gas of different sizes, including possible closure of C3H6-accessible micropores. CMS membranes demonstrate excellent C3H6/C 3H8 separation performance over a wide range of feed pressure, composition and operation temperature. No plasticization was observed at a feed pressure up to 100 psi. The permeation and separation is mainly controlled by diffusion instead of adsorption. CMS membrane experienced a decline in permeance, and an increase in selectivity over time under on-stream C 3H6/C3H8 separation. This aging behavior is due to the reduction in effective pore size and porosity caused by oxygen chemisorption and physical aging of the membrane structure.

CMS tier structure and operation of the experiment-specific tasks in Germany

NASA Astrophysics Data System (ADS)

Nowack, A.

2008-07-01

In Germany, several university institutes and research centres take part in the CMS experiment. Concerning the data analysis, a couple of computing centres at different Tier levels, ranging from Tier 1 to Tier 3, exists at these places. The German Tier 1 centre GridKa at the research centre at Karlsruhe serves all four LHC experiments as well as four non-LHC experiments. With respect to the CMS experiment, GridKa is mainly involved in central tasks. The Tier 2 centre in Germany consists of two sites, one at the research centre DESY at Hamburg and one at RWTH Aachen University, forming a federated Tier 2 centre. Both parts cover different aspects of a Tier 2 centre. The German Tier 3 centres are located at the research centre DESY at Hamburg, at RWTH Aachen University, and at the University of Karlsruhe. Furthermore the building of a German user analysis facility is planned. Since the CMS community in German is rather small, a good cooperation between the different sites is essential. This cooperation includes physical topics as well as technical and operational issues. All available communication channels such as email, phone, monthly video conferences, and regular personal meetings are used. For example, the distribution of data sets is coordinated globally within Germany. Also the CMS-specific services such as the data transfer tool PhEDEx or the Monte Carlo production are operated by people from different sites in order to spread the knowledge widely and increase the redundancy in terms of operators.

Comparative transcriptome analysis of isonuclear-alloplasmic lines unmask key transcription factor genes and metabolic pathways involved in sterility of maize CMS-C.

PubMed

Li, Chuan; Zhao, Zhuofan; Liu, Yongming; Liang, Bing; Guan, Shuxian; Lan, Hai; Wang, Jing; Lu, Yanli; Cao, Moju

2017-01-01

Although C-type cytoplasmic male sterility (CMS-C) is one of the most attractive tools for maize hybrid seed production, the detailed regulation network of the male sterility remains unclear. In order to identify the CMS-C sterility associated genes and/or pathways, the comparison of the transcriptomes between the CMS-C line C48-2 and its isonuclear-alloplasmic maintainer line N48-2 at pollen mother cell stage (PS), an early development stage of microspore, and mononuclear stage (MS), an abortive stage of microspore, were analyzed. 2,069 differentially expressed genes (DEGs) between the two stages were detected and thought to be essential for the spikelet development of N48-2. 453 of the 2,069 DEGs were differentially expressed at MS stage between the two lines and thought to be participated in the process or the causes of microspore abortion. Among the 453 DEGs, 385 (84.99%) genes were down-regulated and only 68 (15.01%) genes were up-regulated in C48-2 at MS stage. The dramatic decreased expression of the four DEGs encoding MYB transcription factors and the DEGs involved in "polyamine metabolic process", "Cutin, suberine and wax biosynthesis", "Fatty acid elongation", "Biosynthesis of unsaturated fatty acids" and "Proline metabolism" might play an important role in the sterility of C48-2. This study will point out some directions for detailed molecular analysis and better understanding of sterility of CMS-C in maize.

Electrophysiological Analysis of human Pluripotent Stem Cell-derived Cardiomyocytes (hPSC-CMs) Using Multi-electrode Arrays (MEAs).

PubMed

Sala, Luca; Ward-van Oostwaard, Dorien; Tertoolen, Leon G J; Mummery, Christine L; Bellin, Milena

2017-05-12

Cardiomyocytes can now be derived with high efficiency from both human embryonic and human induced-Pluripotent Stem Cells (hPSC). hPSC-derived cardiomyocytes (hPSC-CMs) are increasingly recognized as having great value for modeling cardiovascular diseases in humans, especially arrhythmia syndromes. They have also demonstrated relevance as in vitro systems for predicting drug responses, which makes them potentially useful for drug-screening and discovery, safety pharmacology and perhaps eventually for personalized medicine. This would be facilitated by deriving hPSC-CMs from patients or susceptible individuals as hiPSCs. For all applications, however, precise measurement and analysis of hPSC-CM electrical properties are essential for identifying changes due to cardiac ion channel mutations and/or drugs that target ion channels and can cause sudden cardiac death. Compared with manual patch-clamp, multi-electrode array (MEA) devices offer the advantage of allowing medium- to high-throughput recordings. This protocol describes how to dissociate 2D cell cultures of hPSC-CMs to small aggregates and single cells and plate them on MEAs to record their spontaneous electrical activity as field potential. Methods for analyzing the recorded data to extract specific parameters, such as the QT and the RR intervals, are also described here. Changes in these parameters would be expected in hPSC-CMs carrying mutations responsible for cardiac arrhythmias and following addition of specific drugs, allowing detection of those that carry a cardiotoxic risk.

[Molecular cloning and characterization of BcMYBogu, a novel member of the MYB family involved in OguCMS in Brassica campestris ssp. chinensis].

PubMed

Xiang, Xun; Cao, Jia-Shu; Ye, Wan-Zhi; Cui, Hui-Mei; Yu, Jian-Nong

2007-05-01

In the attempt to elucidate the molecular mechanism of CMS. Ogura cytoplasmic male sterile (OguCMS) lines were obtained in Chinese cabbage after interspecific hybridization between Brassica. napus L. OguCMS and B. campestris ssp. chinensis followed by recurrent backcross with B. campestris ssp. chinensis as the pollen donor. The CMS lines were significantly characterized by the whitish anther and indehiscence of anther. The tapetal hypertrophy with excess vacuola-tion was the first observed defective soon after the tetrad stage, subsequently the microspores defected in pollen wall forma-tion, and later the cytoplasm detached from the exine wall and underwent degeneration. With aid of cDNA-AFLP and RACE approaches, we cloned the BcMYBogu(GenBank accession No: EF127861) in Chinese cabbage, which is premature expressed in early and middle stage floral buds of OguCMS lines, and predicted to encode a novel protein with a DNA binding domain: SH[AL]QKY[RF] motif at the N-terminus. Phylogenetic comparison revealed that the BcMYBogu was clustered with AtMYB32, AtMYB26 and AtMYB4, which were indicated to be involved in male sterility in Arabidopsis thaliana. The BcMYBogu transcript was detected in rosette leaves, floral buds and stems by RT-PCR analysis. Compared with the maintainer, the expression level of BcMYBogu was increased in these organs, especially in floral buds of OguCMS lines. Our investigation suggests that BcMYBogu is a new member of the MYB family involved in male sterility in Chinese cabbage.

Column-parallel correlated multiple sampling circuits for CMOS image sensors and their noise reduction effects.

PubMed

Suh, Sungho; Itoh, Shinya; Aoyama, Satoshi; Kawahito, Shoji

2010-01-01

For low-noise complementary metal-oxide-semiconductor (CMOS) image sensors, the reduction of pixel source follower noises is becoming very important. Column-parallel high-gain readout circuits are useful for low-noise CMOS image sensors. This paper presents column-parallel high-gain signal readout circuits, correlated multiple sampling (CMS) circuits and their noise reduction effects. In the CMS, the gain of the noise cancelling is controlled by the number of samplings. It has a similar effect to that of an amplified CDS for the thermal noise but is a little more effective for 1/f and RTS noises. Two types of the CMS with simple integration and folding integration are proposed. In the folding integration, the output signal swing is suppressed by a negative feedback using a comparator and one-bit D-to-A converter. The CMS circuit using the folding integration technique allows to realize a very low-noise level while maintaining a wide dynamic range. The noise reduction effects of their circuits have been investigated with a noise analysis and an implementation of a 1Mpixel pinned photodiode CMOS image sensor. Using 16 samplings, dynamic range of 59.4 dB and noise level of 1.9 e(-) for the simple integration CMS and 75 dB and 2.2 e(-) for the folding integration CMS, respectively, are obtained.

Using Amazon's Elastic Compute Cloud to dynamically scale CMS computational resources

NASA Astrophysics Data System (ADS)

Evans, D.; Fisk, I.; Holzman, B.; Melo, A.; Metson, S.; Pordes, R.; Sheldon, P.; Tiradani, A.

2011-12-01

Large international scientific collaborations such as the Compact Muon Solenoid (CMS) experiment at the Large Hadron Collider have traditionally addressed their data reduction and analysis needs by building and maintaining dedicated computational infrastructure. Emerging cloud computing services such as Amazon's Elastic Compute Cloud (EC2) offer short-term CPU and storage resources with costs based on usage. These services allow experiments to purchase computing resources as needed, without significant prior planning and without long term investments in facilities and their management. We have demonstrated that services such as EC2 can successfully be integrated into the production-computing model of CMS, and find that they work very well as worker nodes. The cost-structure and transient nature of EC2 services makes them inappropriate for some CMS production services and functions. We also found that the resources are not truely "on-demand" as limits and caps on usage are imposed. Our trial workflows allow us to make a cost comparison between EC2 resources and dedicated CMS resources at a University, and conclude that it is most cost effective to purchase dedicated resources for the "base-line" needs of experiments such as CMS. However, if the ability to use cloud computing resources is built into an experiment's software framework before demand requires their use, cloud computing resources make sense for bursting during times when spikes in usage are required.

40 CFR Table 7 to Subpart Mmmmm of... - Applicability of General Provisions to Subpart MMMMM

Code of Federal Regulations, 2010 CFR

2010-07-01

... alternative test method Yes. § 63.7(g) Performance test data analysis, recordkeeping, and reporting Yes. § 63... emissions monitoring systems (CEMS). § 63.8(g) Data reduction Yes Applies as modified by § 63.8794(g). § 63... CMS notifications—date of CMS performance evaluation Yes. § 63.9(g)(2) Use of COMS data No Subpart...

Rapid Electrical Stimulation Increased Cardiac Apoptosis Through Disturbance of Calcium Homeostasis and Mitochondrial Dysfunction in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

PubMed

Geng, Le; Wang, Zidun; Cui, Chang; Zhu, Yue; Shi, Jiaojiao; Wang, Jiaxian; Chen, Minglong

2018-06-15

Heart failure induced by tachycardia, the most common arrhythmia, is frequently observed in clinical practice. This study was designed to investigate the underlying mechanisms. Rapid electrical stimulation (RES) at a frequency of 3 Hz was applied on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for 7 days, with 8 h/day and 24 h/day set to represent short-term and long-term tachycardia, respectively. Age-matched hiPSC-CMs without electrical stimulation or with slow electrical stimulation (1 Hz) were set as no electrical stimulation (NES) control or low-frequency electrical stimulation (LES) control. Following stimulation, JC-1 staining flow cytometry analysis was performed to examine mitochondrial conditions. Apoptosis in hiPSC-CMs was evaluated using Hoechst staining and Annexin V/propidium iodide (AV/PI) staining flow cytometry analysis. Calcium transients and L-type calcium currents were recorded to evaluate calcium homeostasis. Western blotting and qPCR were performed to evaluate the protein and mRNA expression levels of apoptosis-related genes and calcium homeostasis-regulated genes. Compared to the controls, hiPSC-CMs following RES presented mitochondrial dysfunction and an increased apoptotic percentage. Amplitudes of calcium transients and L-type calcium currents were significantly decreased in hiPSC-CMs with RES. Molecular analysis demonstrated upregulated expression of Caspase3 and increased Bax/Bcl-2 ratio. Genes related to calcium re-sequence were downregulated, while phosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII) was significantly upregulated following RES. There was no significant difference between the NES control and LES control groups in these aspects. Inhibition of CaMKII with 1 µM KN93 partly reversed these adverse effects of RES. RES on hiPSC-CMs disturbed calcium homeostasis, which led to mitochondrial stress, promoted cell apoptosis and caused electrophysiological remodeling in a time-dependent manner. CaMKII played a central role in the damages induced by RES, pharmacological inhibition of CaMKII activity partly reversed the adverse effects of RES on both structural and electrophysiological properties of cells. © 2018 The Author(s). Published by S. Karger AG, Basel.

A preliminary identification of Rf*-A619, a novel restorer gene for CMS-C in maize (Zea mays L.).

PubMed

Yongming, Liu; Zhuofan, Zhao; Yanli, Lu; Chuan, Li; Jing, Wang; Boxiao, Dong; Bing, Liang; Tao, Qiu; Wenbing, Zeng; Moju, Cao

2016-01-01

C-type cytoplasmic male sterility (CMS-C) is widely utilized for hybrid maize seed production. However, genetic mechanisms underlying the fertility restoration are very complicated. At present, there is a divergence on the number of fertility restorer genes in maize inbred line A619 for CMS-C. To further elucidate the restoring mechanism of A619, we used genetic analysis and molecular markers to confirm the restorer genes of maize inbred line A619 for C-type male sterile line C48-2 in this study. Firstly, the fertility segregations of (C48-2 × A619)F 2 populations were investigated under three environments during 2013-2015. The segregation ratio of fertile and sterile plants in the F 2 population fit to 15:1 via chi-square test and this result suggested that there are two dominant restorer genes in A619 for CMS-C, i.e., Rf4 and a novel gene named Rf*-A619 . Next, based on the sequence differences between Rf4 and its recessive allelic rf4 , a novel dominant marker F2/R2 was developed and validated to genotyping Rf4 in the F 2 population. Through genotypic analysis, we found that there were a certain amount of fertile individuals without Rf4 which accounted for 3/16 in the F 2 population via chi-square test at the 0.05 level. These results provided another proof to sustain that the inbred line A619 contains one additional restorer gene for CMS-C fertility restoration except Rf4 . At last, we used one SSR marker which is tightly linked with the dominant restorer gene Rf5 to analyze those fertile plants without Rf4 in the F 2 population. The PCR amplification results showed that Rf*-A619 is not allelic to Rf5 but a novel restorer gene for CMS-C. These results not only provide a basis for the mapping and characterization of a novel restorer gene but also give a new insight into the mechanism of CMS-C fertility restoration.

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...

What are the roles of clinical nurses and midwife specialists?

PubMed

Wickham, Sheelagh

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

Recessive variants of MuSK are associated with late onset CMS and predominant limb girdle weakness.

PubMed

Owen, David; Töpf, Ana; Preethish-Kumar, Veeramani; Lorenzoni, Paulo José; Vroling, Bas; Scola, Rosana Herminia; Dias-Tosta, Elza; Geraldo, Argemiro; Polavarapu, Kiran; Nashi, Saraswati; Cox, Daniel; Evangelista, Teresinha; Dawson, John; Thompson, Rachel; Senderek, Jan; Laurie, Steven; Beltran, Sergi; Gut, Marta; Gut, Ivo; Nalini, Atchayaram; Lochmüller, Hanns

2018-04-28

Congenital myasthenic syndrome (CMS) is a heterogeneous disorder that causes fatigable muscle weakness. CMS has been associated with variants in the MuSK gene and, to date, 16 patients have been reported. MuSK-CMS patients present a different phenotypic pattern of limb girdle weakness. Here, we describe four additional patients and discuss the phenotypic and clinical relationship with those previously reported. Two novel damaging missense variants are described: c.1742T > A; p.I581N found in homozygosis, and c.1634T > C; p.L545P found in compound heterozygosis with p.R166*. The reported patients had predominant limb girdle weakness with symptom onset at 12, 17, 18, and 30 years of age, and the majority exhibited a good clinical response to Salbutamol therapy, but not to esterase inhibitors. Meta-analysis including previously reported variants revealed an increased likelihood of a severe, respiratory phenotype with null alleles. Missense variants exclusively affecting the kinase domain, but not the catalytic site, are associated with late onset. These data refine the phenotype associated with MuSK-related CMS. © 2018 Wiley Periodicals, Inc.

CRAB3: Establishing a new generation of services for distributed analysis at CMS

NASA Astrophysics Data System (ADS)

Cinquilli, M.; Spiga, D.; Grandi, C.; Hernàndez, J. M.; Konstantinov, P.; Mascheroni, M.; Riahi, H.; Vaandering, E.

2012-12-01

In CMS Computing the highest priorities for analysis tools are the improvement of the end users’ ability to produce and publish reliable samples and analysis results as well as a transition to a sustainable development and operations model. To achieve these goals CMS decided to incorporate analysis processing into the same framework as data and simulation processing. This strategy foresees that all workload tools (TierO, Tier1, production, analysis) share a common core with long term maintainability as well as the standardization of the operator interfaces. The re-engineered analysis workload manager, called CRAB3, makes use of newer technologies, such as RESTFul based web services and NoSQL Databases, aiming to increase the scalability and reliability of the system. As opposed to CRAB2, in CRAB3 all work is centrally injected and managed in a global queue. A pool of agents, which can be geographically distributed, consumes work from the central services serving the user tasks. The new architecture of CRAB substantially changes the deployment model and operations activities. In this paper we present the implementation of CRAB3, emphasizing how the new architecture improves the workflow automation and simplifies maintainability. In particular, we will highlight the impact of the new design on daily operations.

Effects of Ether vs. Ester Linkage on Lipid Bilayer Structure and Water Permeability

PubMed Central

Guler, S. Deren; Ghosh, D. Dipon; Pan, Jianjun; Matthai, John C.; Zeidel, Mark L.; Nagle, John F.; Tristram-Nagle, Stephanie

2009-01-01

The structure and water permeability of bilayers composed of the ether linked lipid, dihexadecylphosphatidylcholine (DHPC), were studied and compared with the ester linked lipid, dipalmitoylphosphaditdylcholine (DPPC). Wide angle x-ray scattering on oriented bilayers in the fluid phase indicate that the area per lipid A is slightly larger for DHPC than for DPPC. Low angle x-ray scattering yields A=65.1Å2 for DHPC at 48°C. LAXS data provide the bending modulus, KC=4.2×10−13erg, and the Hamaker parameter H=7.2×10−14erg for the van der Waals attractive interaction between neighboring bilayers. For the low temperature phases with ordered hydrocarbon chains, we confirm the transition from a tilted Lß’ gel phase to an untilted, interdigitated LßI phase as the sample hydrates at 20°C. Our measurement of water permeability, Pf=0.022 cm/s at 48 °C for fluid phase DHPC is slightly smaller than that of DPPC, (Pf=0.027 cm/s) at 50 °C, consistent with our triple slab theory of permeability. PMID:19416724

Organellar Genomes from a ∼5,000-Year-Old Archaeological Maize Sample Are Closely Related to NB Genotype

PubMed Central

Pérez-Zamorano, Bernardo; Vallebueno-Estrada, Miguel; Martínez González, Javier; García Cook, Angel; Montiel, Rafael; Vielle-Calzada, Jean-Philippe

2017-01-01

The story of how preColumbian civilizations developed goes hand-in-hand with the process of plant domestication by Mesoamerican inhabitants. Here, we present the almost complete sequence of a mitochondrial genome and a partial chloroplast genome from an archaeological maize sample collected at the Valley of Tehuacán, México. Accelerator mass spectrometry dated the maize sample to be 5,040–5,300 years before present (95% probability). Phylogenetic analysis of the mitochondrial genome shows that the archaeological sample branches basal to the other Zea mays genomes, as expected. However, this analysis also indicates that fertile genotype NB is closely related to the archaeological maize sample and evolved before cytoplasmic male sterility genotypes (CMS-S, CMS-T, and CMS-C), thus contradicting previous phylogenetic analysis of mitochondrial genomes from maize. We show that maximum-likelihood infers a tree where CMS genotypes branch at the base of the tree when including sites that have a relative fast rate of evolution thus suggesting long-branch attraction. We also show that Bayesian analysis infer a topology where NB and the archaeological maize sample are at the base of the tree even when including faster sites. We therefore suggest that previous trees suffered from long-branch attraction. We also show that the phylogenetic analysis of the ancient chloroplast is congruent with genotype NB to be more closely related to the archaeological maize sample. As shown here, the inclusion of ancient genomes on phylogenetic trees greatly improves our understanding of the domestication process of maize, one of the most important crops worldwide. PMID:28338960

Comparative transcriptome analysis of isonuclear-alloplasmic lines unmask key transcription factor genes and metabolic pathways involved in sterility of maize CMS-C

PubMed Central

Liu, Yongming; Liang, Bing; Guan, Shuxian; Lan, Hai; Wang, Jing; Lu, Yanli

2017-01-01

Although C-type cytoplasmic male sterility (CMS-C) is one of the most attractive tools for maize hybrid seed production, the detailed regulation network of the male sterility remains unclear. In order to identify the CMS-C sterility associated genes and/or pathways, the comparison of the transcriptomes between the CMS-C line C48-2 and its isonuclear-alloplasmic maintainer line N48-2 at pollen mother cell stage (PS), an early development stage of microspore, and mononuclear stage (MS), an abortive stage of microspore, were analyzed. 2,069 differentially expressed genes (DEGs) between the two stages were detected and thought to be essential for the spikelet development of N48-2. 453 of the 2,069 DEGs were differentially expressed at MS stage between the two lines and thought to be participated in the process or the causes of microspore abortion. Among the 453 DEGs, 385 (84.99%) genes were down-regulated and only 68 (15.01%) genes were up-regulated in C48-2 at MS stage. The dramatic decreased expression of the four DEGs encoding MYB transcription factors and the DEGs involved in “polyamine metabolic process”, “Cutin, suberine and wax biosynthesis”, “Fatty acid elongation”, “Biosynthesis of unsaturated fatty acids” and “Proline metabolism” might play an important role in the sterility of C48-2. This study will point out some directions for detailed molecular analysis and better understanding of sterility of CMS-C in maize. PMID:28584730

Human iPSC-derived myocardium-on-chip with capillary-like flow for personalized medicine.

PubMed

Ellis, Bradley W; Acun, Aylin; Can, U Isik; Zorlutuna, Pinar

2017-03-01

The heart wall tissue, or the myocardium, is one of the main targets in cardiovascular disease prevention and treatment. Animal models have not been sufficient in mimicking the human myocardium as evident by the very low clinical translation rates of cardiovascular drugs. Additionally, current in vitro models of the human myocardium possess several shortcomings such as lack of physiologically relevant co-culture of myocardial cells, lack of a 3D biomimetic environment, and the use of non-human cells. In this study, we address these shortcomings through the design and manufacture of a myocardium-on-chip (MOC) using 3D cell-laden hydrogel constructs and human induced pluripotent stem cell (hiPSC) derived myocardial cells. The MOC utilizes 3D spatially controlled co-culture of hiPSC derived cardiomyocytes (iCMs) and hiPSC derived endothelial cells (iECs) integrated among iCMs as well as in capillary-like side channels, to better mimic the microvasculature seen in native myocardium. We first fully characterized iCMs using immunostaining, genetic, and electrochemical analysis and iECs through immunostaining and alignment analysis to ensure their functionality, and then seeded these cells sequentially into the MOC device. We showed that iECs could be cultured within the microfluidic device without losing their phenotypic lineage commitment, and align with the flow upon physiological level shear stresses. We were able to incorporate iCMs within the device in a spatially controlled manner with the help of photocrosslinkable polymers. The iCMs were shown to be viable and functional within the device up to 7 days, and were integrated with the iECs. The iCMs and iECs in this study were derived from the same hiPSC cell line, essentially mimicking the myocardium of an individual human patient. Such devices are essential for personalized medicine studies where the individual drug response of patients with different genetic backgrounds can be tested in a physiologically relevant manner.

Human iPSC-derived myocardium-on-chip with capillary-like flow for personalized medicine

PubMed Central

Ellis, Bradley W.; Acun, Aylin; Can, U. Isik; Zorlutuna, Pinar

2017-01-01

The heart wall tissue, or the myocardium, is one of the main targets in cardiovascular disease prevention and treatment. Animal models have not been sufficient in mimicking the human myocardium as evident by the very low clinical translation rates of cardiovascular drugs. Additionally, current in vitro models of the human myocardium possess several shortcomings such as lack of physiologically relevant co-culture of myocardial cells, lack of a 3D biomimetic environment, and the use of non-human cells. In this study, we address these shortcomings through the design and manufacture of a myocardium-on-chip (MOC) using 3D cell-laden hydrogel constructs and human induced pluripotent stem cell (hiPSC) derived myocardial cells. The MOC utilizes 3D spatially controlled co-culture of hiPSC derived cardiomyocytes (iCMs) and hiPSC derived endothelial cells (iECs) integrated among iCMs as well as in capillary-like side channels, to better mimic the microvasculature seen in native myocardium. We first fully characterized iCMs using immunostaining, genetic, and electrochemical analysis and iECs through immunostaining and alignment analysis to ensure their functionality, and then seeded these cells sequentially into the MOC device. We showed that iECs could be cultured within the microfluidic device without losing their phenotypic lineage commitment, and align with the flow upon physiological level shear stresses. We were able to incorporate iCMs within the device in a spatially controlled manner with the help of photocrosslinkable polymers. The iCMs were shown to be viable and functional within the device up to 7 days, and were integrated with the iECs. The iCMs and iECs in this study were derived from the same hiPSC cell line, essentially mimicking the myocardium of an individual human patient. Such devices are essential for personalized medicine studies where the individual drug response of patients with different genetic backgrounds can be tested in a physiologically relevant manner. PMID:28396709

Diode Laser Stapedotomy vs Conventional Stapedotomy in Otosclerosis: A Double-Blinded Randomized Clinical Trial.

PubMed

Parida, Pradipta Kumar; Kalaiarasi, Raja; Gopalakrishnan, Surianarayana

2016-06-01

To assess and compare the efficacy of diode laser stapedotomy (DLS) and conventional manual stapedotomy (CMS) in the treatment of otosclerosis. Randomized clinical trial. Tertiary health center. We randomly assigned 60 patients with otosclerosis planned for primary stapedotomy to receive either DLS or CMS. Primary outcome measure was hearing gain measured by pure-tone audiometry (PTA) performed preoperatively and postoperatively. Hearing gain was compared within and between the groups. Secondary outcome measures were the incidence of intraoperative (bleeding and fractured footplate) and postoperative (vomiting, vertigo, sensorineural hearing loss, tinnitus, facial nerve paralysis, and hospital stay) morbidities. Sixty primary stapedotomies (30 in the CMS group and 30 in the DLS group) done for 60 patients (male, n = 42; female, n = 18) were included in the analysis. Preoperative mean air-bone (AB) gap in the DLS and CMS groups was 38.51 ± 8.643 dB and 36.42 ± 8.678 dB, respectively. Mean AB gap at 6 month was 10.86 ± 5.383 dB and 11.05 ± 5.236 dB in the CMS and DLS groups, respectively. Air conduction was improved by 24.98 ± 5.348 dB in the DLS group and 24.08 ± 5.911 dB in the CMS group at 6 months. No statistically significant differences were found in hearing gain between the 2 groups at 6 months (P > .05). A decreased rate and severity of intraoperative bleeding, postoperative vertigo, and vomiting were observed with the diode laser (0%, 6.6%, and 10%) compared with the conventional technique (16.7%, 16.7%, and 16.7%), but these differences were not statistically significant (P > .05). Hearing outcomes and complications of DLS were similar to CMS. These study findings confirm the efficacy of the diode laser in stapedotomy, but DLS offers no advantages over CMS for otosclerosis surgery. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Comparing technical efficiency of farms with an automatic milking system and a conventional milking system.

PubMed

Steeneveld, W; Tauer, L W; Hogeveen, H; Oude Lansink, A G J M

2012-12-01

Changing from a conventional milking system (CMS) to an automatic milking system (AMS) necessitates a new management approach and a corresponding change in labor tasks. Together with labor savings, AMS farms have been found to have higher capital costs, primarily because of higher maintenance costs and depreciation. Therefore, it is hypothesized that AMS farms differ from CMS farms in capital:labor ratio and possibly their technical efficiency, at least during a transition learning period. The current study used actual farm accounting data from dairy farms in the Netherlands with an AMS and a CMS to investigate the empirical substitution of capital for labor in the AMS farms and to determine if the technical efficiency of the AMS farms differed from the CMS farms. The technical efficiency estimates were obtained with data envelopment analysis. The 63 AMS farms and the 337 CMS farms in the data set did not differ in general farm characteristics such as the number of cows, number of hectares, and the amount of milk quota. Farms with AMS have significantly higher capital costs (€12.71 per 100 kg of milk) than CMS farms (€10.10 per 100 kg of milk). Total labor costs and net outputs were not significantly different between AMS and CMS farms. A clear substitution of capital for labor with the adoption of an AMS could not be observed. Although the AMS farms have a slightly lower technical efficiency (0.76) than the CMS farms (0.78), a significant difference in these estimates was not observed. This indicates that the farms were not different in their ability to use inputs (capital, labor, cows, and land) to produce outputs (total farm revenues). The technical efficiency of farms invested in an AMS in 2008 or earlier was not different from the farms invested in 2009 or 2010, indicating that a learning effect during the transition period was not observed. The results indicate that the economic performance of AMS and CMS farms are similar. What these results show is that other than higher capital costs, the use of AMS rather than a CMS does not affect farm efficiency and that the learning costs to use an AMS are not present as measured by any fall in technical efficiency. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Impact of carbonaceous materials in soil on the transport of soil-bound PAHs during rainfall-runoff events.

PubMed

Luo, Xiaolin; Zheng, Yi; Wu, Bin; Lin, Zhongrong; Han, Feng; Zhang, Wei; Wang, Xuejun

2013-11-01

Polycyclic Aromatic Hydrocarbons (PAHs) transported from contaminated soils by surface runoff pose significant risk for aquatic ecosystems. Based on a rainfall-runoff simulation experiment, this study investigated the impact of carbonaceous materials (CMs) in soil, identified by organic petrology analysis, on the transport of soil-bound PAHs under rainfall conditions. The hypothesis that composition of soil organic matter significantly impacts the enrichment and transport of PAHs was proved. CMs in soil, varying significantly in content, mobility and adsorption capacity, act differently on the transport of PAHs. Anthropogenic CMs like black carbon (BC) largely control the transport, as PAHs may be preferentially attached to them. Eventually, this study led to a rethink of the traditional enrichment theory. An important implication is that CMs in soil have to be explicitly considered to appropriately model the nonpoint source pollution of PAHs (possibly other hydrophobic chemicals as well) and assess its environmental risk. Copyright © 2013 Elsevier Ltd. All rights reserved.

Conductivity and transit time estimates of a soil liner

USGS Publications Warehouse

Krapac, I.G.; Cartwright, K.; Panno, S.V.; Hensel, B.R.; Rehfeldt, K.H.; Herzog, B.L.

1990-01-01

A field-scale soil linear was built to assess the feasibilty of constructing a liner to meet the saturated hydraulic conductivity requirement of the U.S. EPA (i.e., less than 1 ?? 10-7 cm/s), and to determine the breakthrough and transit times of water and tracers through the liner. The liner, 8 ?? 15 ?? 0.9 m, was constructed in 15-cm compacted lifts using a 20,037-kg pad-foot compactor and standard engineering practices. Estimated saturated hydraulic conductivities were 2.4 ?? 10-9 cm/s, based on data from large-ring infiltrometers; 4.0 ?? 10-8 cm/s from small-ring infiltrometers; and 5.0 ?? 10-8 cm/s from a water-balance analysis. These estimates were derived from 1 year of monitoring water infiltration into the linear. Breakthrough of tracers at the base of the liner was estimated to be between 2 and 13 years, depending on the method of calculation and the assumptions used in the calculation.

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

PubMed

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

2014-12-15

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

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.

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.

Let-7 family of microRNA is required for maturation and adult-like metabolism in stem cell-derived cardiomyocytes

PubMed Central

Kuppusamy, Kavitha T.; Jones, Daniel C.; Sperber, Henrik; Madan, Anup; Fischer, Karin A.; Rodriguez, Marita L.; Pabon, Lil; Zhu, Wei-Zhong; Tulloch, Nathaniel L.; Yang, Xiulan; Sniadecki, Nathan J.; Laflamme, Michael A.; Murry, Charles E.; Ruohola-Baker, Hannele

2015-01-01

In metazoans, transition from fetal to adult heart is accompanied by a switch in energy metabolism-glycolysis to fatty acid oxidation. The molecular factors regulating this metabolic switch remain largely unexplored. We first demonstrate that the molecular signatures in 1-year (y) matured human embryonic stem cell-derived cardiomyocytes (hESC-CMs) are similar to those seen in in vivo-derived mature cardiac tissues, thus making them an excellent model to study human cardiac maturation. We further show that let-7 is the most highly up-regulated microRNA (miRNA) family during in vitro human cardiac maturation. Gain- and loss-of-function analyses of let-7g in hESC-CMs demonstrate it is both required and sufficient for maturation, but not for early differentiation of CMs. Overexpression of let-7 family members in hESC-CMs enhances cell size, sarcomere length, force of contraction, and respiratory capacity. Interestingly, large-scale expression data, target analysis, and metabolic flux assays suggest this let-7–driven CM maturation could be a result of down-regulation of the phosphoinositide 3 kinase (PI3K)/AKT protein kinase/insulin pathway and an up-regulation of fatty acid metabolism. These results indicate let-7 is an important mediator in augmenting metabolic energetics in maturing CMs. Promoting maturation of hESC-CMs with let-7 overexpression will be highly significant for basic and applied research. PMID:25964336

Efficient monitoring of CRAB jobs at CMS

NASA Astrophysics Data System (ADS)

Silva, J. M. D.; Balcas, J.; Belforte, S.; Ciangottini, D.; Mascheroni, M.; Rupeika, E. A.; Ivanov, T. T.; Hernandez, J. M.; Vaandering, E.

2017-10-01

CRAB is a tool used for distributed analysis of CMS data. Users can submit sets of jobs with similar requirements (tasks) with a single request. CRAB uses a client-server architecture, where a lightweight client, a server, and ancillary services work together and are maintained by CMS operators at CERN. As with most complex software, good monitoring tools are crucial for efficient use and longterm maintainability. This work gives an overview of the monitoring tools developed to ensure the CRAB server and infrastructure are functional, help operators debug user problems, and minimize overhead and operating cost. This work also illustrates the design choices and gives a report on our experience with the tools we developed and the external ones we used.

The application of capillary microsampling in GLP toxicology studies.

PubMed

Verhaeghe, Tom; Dillen, Lieve; Stieltjes, Hans; Zwart, Loeckie de; Feyen, Bianca; Diels, Luc; Vroman, Ann; Timmerman, Philip

2017-04-01

Capillary microsampling (CMS) to collect microplasma volumes is gradually replacing traditional, larger volume sampling from rats in GLP toxicology studies. About 32 µl of blood is collected with a capillary, processed to plasma and stored in a 10- or 4-µl capillary which is washed out further downstream in the laboratory. CMS has been standardized with respect to materials, assay validation experiments and application for sample analysis. The implementation of CMS has resulted in blood volume reductions in the rat from 300 to 32 µl per time point and the elimination of toxicokinetic satellite groups in the majority of the rat GLP toxicology studies. The technique has been successfully applied in 26 GLP studies for 12 different projects thus far.

Efficient Monitoring of CRAB Jobs at CMS

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

Silva, J. M.D.; Balcas, J.; Belforte, S.

CRAB is a tool used for distributed analysis of CMS data. Users can submit sets of jobs with similar requirements (tasks) with a single request. CRAB uses a client-server architecture, where a lightweight client, a server, and ancillary services work together and are maintained by CMS operators at CERN. As with most complex software, good monitoring tools are crucial for efficient use and longterm maintainability. This work gives an overview of the monitoring tools developed to ensure the CRAB server and infrastructure are functional, help operators debug user problems, and minimize overhead and operating cost. This work also illustrates themore » design choices and gives a report on our experience with the tools we developed and the external ones we used.« less

Measurement of the W charge asymmetry in production with jets using 5 inverse-femtobarns of data measured at center of mass energy = 7TeV with CMS

NASA Astrophysics Data System (ADS)

Lawson, Philip Daniel

A measurement of the electron charge asymmetry in p+p→W production in association with jets at sqrt{s}=7 TeV is presented. The dataset corresponds to an integrated luminosity of L=5fb-1 recorded by the CMS detector in proton-proton collisions at the LHC. The sample represents a large increase in statistical precision with respect to previous CMS results and describes a first study of charge asymmetry measured in p+p→W+1 jet events. Full comparisons to previous results and theoretical predictions are provided and recommendations for extending the analysis to produce valuable input for future PDF models are made.

Comprehensive monitoring for heterogeneous geographically distributed storage

DOE PAGES

Ratnikova, Natalia; Karavakis, E.; Lammel, S.; ...

2015-12-23

Storage capacity at CMS Tier-1 and Tier-2 sites reached over 100 Petabytes in 2014, and will be substantially increased during Run 2 data taking. The allocation of storage for the individual users analysis data, which is not accounted as a centrally managed storage space, will be increased to up to 40%. For comprehensive tracking and monitoring of the storage utilization across all participating sites, CMS developed a space monitoring system, which provides a central view of the geographically dispersed heterogeneous storage systems. The first prototype was deployed at pilot sites in summer 2014, and has been substantially reworked since then.more » In this study, we discuss the functionality and our experience of system deployment and operation on the full CMS scale.« less

Single-Cell Functional Analysis of Stem-Cell Derived Cardiomyocytes on Micropatterned Flexible Substrates.

PubMed

Kijlstra, Jan David; Hu, Dongjian; van der Meer, Peter; Domian, Ibrahim J

2017-11-15

Human pluripotent stem-cell derived cardiomyocytes (hPSC-CMs) hold great promise for applications in human disease modeling, drug discovery, cardiotoxicity screening, and, ultimately, regenerative medicine. The ability to study multiple parameters of hPSC-CM function, such as contractile and electrical activity, calcium cycling, and force generation, is therefore of paramount importance. hPSC-CMs cultured on stiff substrates like glass or polystyrene do not have the ability to shorten during contraction, making them less suitable for the study of hPSC-CM contractile function. Other approaches require highly specialized hardware and are difficult to reproduce. Here we describe a protocol for the preparation of hPSC-CMs on soft substrates that enable shortening, and subsequently the simultaneous quantitative analysis of their contractile and electrical activity, calcium cycling, and force generation at single-cell resolution. This protocol requires only affordable and readily available materials and works with standard imaging hardware. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Copy number analysis reveals a novel multiexon deletion of the COLQ gene in congenital myasthenia.

PubMed

Wang, Wei; Wu, Yanhong; Wang, Chen; Jiao, Jinsong; Klein, Christopher J

2016-12-01

Congenital myasthenic syndrome (CMS) is genetically and clinically heterogeneous. 1 Despite a considerable number of causal genes discovered, many patients are left without a specific diagnosis after genetic testing. The presumption is that novel genes yet to be discovered will account for the majority of such patients. However, it is also possible that we are neglecting a type of genetic variation: copy number changes (>50 bp) as causal for some of these patients. Next-generation sequencing (NGS) can simultaneously screen all known causal genes 2 and is increasingly being validated to have a potential to identify copy number changes. 3 We present a CMS case who did not receive a genetic diagnosis from previous Sanger sequencing, but through a novel copy number analysis algorithm integrated into our targeted NGS panel, we discovered a novel copy number mutation in the COLQ gene and made a genetic diagnosis. This discovery expands the genotype-phenotype correlation of CMS, leads to improved genetic counsel, and allows for specific pharmacologic treatment. 1 .

Cost-Benefit Analysis for ECIA Chapter 1 and State DPPF Programs Comparing Groups Receiving Regular Program Instruction and Groups Receiving Computer Assisted Instruction/Computer Management System (CAI/CMS). 1986-87.

ERIC Educational Resources Information Center

Chamberlain, Ed

A cost benefit study was conducted to determine the effectiveness of a computer assisted instruction/computer management system (CAI/CMS) as an alternative to conventional methods of teaching reading within Chapter 1 and DPPF funded programs of the Columbus (Ohio) Public Schools. The Chapter 1 funded Compensatory Language Experiences and Reading…

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...

Noninvasive Detection and Imaging of Molecular Markers in Live Cardiomyocytes Derived from Human Embryonic Stem Cells

PubMed Central

Pascut, Flavius C.; Goh, Huey T.; Welch, Nathan; Buttery, Lee D.; Denning, Chris; Notingher, Ioan

2011-01-01

Raman microspectroscopy (RMS) was used to detect and image molecular markers specific to cardiomyocytes (CMs) derived from human embryonic stem cells (hESCs). This technique is noninvasive and thus can be used to discriminate individual live CMs within highly heterogeneous cell populations. Principal component analysis (PCA) of the Raman spectra was used to build a classification model for identification of individual CMs. Retrospective immunostaining imaging was used as the gold standard for phenotypic identification of each cell. We were able to discriminate CMs from other phenotypes with >97% specificity and >96% sensitivity, as calculated with the use of cross-validation algorithms (target 100% specificity). A comparison between Raman spectral images corresponding to selected Raman bands identified by the PCA model and immunostaining of the same cells allowed assignment of the Raman spectral markers. We conclude that glycogen is responsible for the discrimination of CMs, whereas myofibril proteins have a lesser contribution. This study demonstrates the potential of RMS for allowing the noninvasive phenotypic identification of hESC progeny. With further development, such label-free optical techniques may enable the separation of high-purity cell populations with mature phenotypes, and provide repeated measurements to monitor time-dependent molecular changes in live hESCs during differentiation in vitro. PMID:21190678

Examination of the interaction of different lighting conditions and chronic mild stress in animal model.

PubMed

Muller, A; Gal, N; Betlehem, J; Fuller, N; Acs, P; Kovacs, G L; Fusz, K; Jozsa, R; Olah, A

2015-09-01

We examined the effects of different shift work schedules and chronic mild stress (CMS) on mood using animal model. The most common international shift work schedules in nursing were applied by three groups of Wistar-rats and a control group with normal light-dark cycle. One subgroup from each group was subjected to CMS. Levels of anxiety and emotional life were evaluated in light-dark box. Differences between the groups according to independent and dependent variables were examined with one- and two-way analysis of variance, with a significance level defined at p < 0.05. Interaction of lighting regimen and CMS was proved to be significant according to time spent in the light compartment and the average number of changes between the light and dark compartments. Results of our examination confirm that the changes of lighting conditions evocate anxiety more prominently than CMS. No significant differences were found between the results of the low rotating group and the control group, supposing that this schedule is the least harmful to health. Our results on the association between the use of lighting regimens and the level of CMS provide evidence that the fast rotating shift work schedule puts the heaviest load on the organism of animals.

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2013-01-01

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

CRISPR/Cas9 editing in human pluripotent stem cell-cardiomyocytes highlights arrhythmias, hypocontractility, and energy depletion as potential therapeutic targets for hypertrophic cardiomyopathy.

PubMed

Mosqueira, Diogo; Mannhardt, Ingra; Bhagwan, Jamie R; Lis-Slimak, Katarzyna; Katili, Puspita; Scott, Elizabeth; Hassan, Mustafa; Prondzynski, Maksymilian; Harmer, Stephen C; Tinker, Andrew; Smith, James G W; Carrier, Lucie; Williams, Philip M; Gaffney, Daniel; Eschenhagen, Thomas; Hansen, Arne; Denning, Chris

2018-05-08

Sarcomeric gene mutations frequently underlie hypertrophic cardiomyopathy (HCM), a prevalent and complex condition leading to left ventricle thickening and heart dysfunction. We evaluated isogenic genome-edited human pluripotent stem cell-cardiomyocytes (hPSC-CM) for their validity to model, and add clarity to, HCM. CRISPR/Cas9 editing produced 11 variants of the HCM-causing mutation c.C9123T-MYH7 [(p.R453C-β-myosin heavy chain (MHC)] in 3 independent hPSC lines. Isogenic sets were differentiated to hPSC-CMs for high-throughput, non-subjective molecular and functional assessment using 12 approaches in 2D monolayers and/or 3D engineered heart tissues. Although immature, edited hPSC-CMs exhibited the main hallmarks of HCM (hypertrophy, multi-nucleation, hypertrophic marker expression, sarcomeric disarray). Functional evaluation supported the energy depletion model due to higher metabolic respiration activity, accompanied by abnormalities in calcium handling, arrhythmias, and contraction force. Partial phenotypic rescue was achieved with ranolazine but not omecamtiv mecarbil, while RNAseq highlighted potentially novel molecular targets. Our holistic and comprehensive approach showed that energy depletion affected core cardiomyocyte functionality. The engineered R453C-βMHC-mutation triggered compensatory responses in hPSC-CMs, causing increased ATP production and αMHC to energy-efficient βMHC switching. We showed that pharmacological rescue of arrhythmias was possible, while MHY7: MYH6 and mutant: wild-type MYH7 ratios may be diagnostic, and previously undescribed lncRNAs and gene modifiers are suggestive of new mechanisms.

CMS Physics Technical Design Report, Volume II: Physics Performance

NASA Astrophysics Data System (ADS)

CMS Collaboration

2007-06-01

CMS is a general purpose experiment, designed to study the physics of pp collisions at 14 TeV at the Large Hadron Collider (LHC). It currently involves more than 2000 physicists from more than 150 institutes and 37 countries. The LHC will provide extraordinary opportunities for particle physics based on its unprecedented collision energy and luminosity when it begins operation in 2007. The principal aim of this report is to present the strategy of CMS to explore the rich physics programme offered by the LHC. This volume demonstrates the physics capability of the CMS experiment. The prime goals of CMS are to explore physics at the TeV scale and to study the mechanism of electroweak symmetry breaking—through the discovery of the Higgs particle or otherwise. To carry out this task, CMS must be prepared to search for new particles, such as the Higgs boson or supersymmetric partners of the Standard Model particles, from the start-up of the LHC since new physics at the TeV scale may manifest itself with modest data samples of the order of a few fb -1 or less. The analysis tools that have been developed are applied to study in great detail and with all the methodology of performing an analysis on CMS data specific benchmark processes upon which to gauge the performance of CMS. These processes cover several Higgs boson decay channels, the production and decay of new particles such as Z' and supersymmetric particles, B s production and processes in heavy ion collisions. The simulation of these benchmark processes includes subtle effects such as possible detector miscalibration and misalignment. Besides these benchmark processes, the physics reach of CMS is studied for a large number of signatures arising in the Standard Model and also in theories beyond the Standard Model for integrated luminosities ranging from 1 fb -1 to 30 fb -1 . The Standard Model processes include QCD, B -physics, diffraction, detailed studies of the top quark properties, and electroweak physics topics such as the W and Z 0 boson properties. The production and decay of the Higgs particle is studied for many observable decays, and the precision with which the Higgs boson properties can be derived is determined. About ten different supersymmetry benchmark points are analysed using full simulation. The CMS discovery reach is evaluated in the SUSY parameter space covering a large variety of decay signatures. Furthermore, the discovery reach for a plethora of alternative models for new physics is explored, notably extra dimensions, new vector boson high mass states, little Higgs models, technicolour and others. Methods to discriminate between models have been investigated. This report is organized as follows. Chapter 1, the Introduction, describes the context of this document. Chapters 2 6 describe examples of full analyses, with photons, electrons, muons, jets, missing E T , B-mesons and τ's, and for quarkonia in heavy ion collisions. Chapters 7 15 describe the physics reach for Standard Model processes, Higgs discovery and searches for new physics beyond the Standard Model.

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...

Data Bookkeeping Service 3 - Providing Event Metadata in CMS

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

Giffels, Manuel; Guo, Y.; Riley, Daniel

The Data Bookkeeping Service 3 provides a catalog of event metadata for Monte Carlo and recorded data of the Compact Muon Solenoid (CMS) experiment at the Large Hadron Collider (LHC) at CERN, Geneva. It comprises all necessary information for tracking datasets, their processing history and associations between runs, files and datasets, on a large scale of about 200, 000 datasets and more than 40 million files, which adds up in around 700 GB of metadata. The DBS is an essential part of the CMS Data Management and Workload Management (DMWM) systems [1], all kind of data-processing like Monte Carlo production,more » processing of recorded event data as well as physics analysis done by the users are heavily relying on the information stored in DBS.« less

Diphoton searches (CMS)

NASA Astrophysics Data System (ADS)

Quittnat, Milena

2017-12-01

The search for high mass resonances decaying into two photons is well motivated by many physics scenarios beyond the standard model. This note summarizes the results of this search in proton-proton collision with a center-of-mass energy of √s = 13 TeV and an integrated luminosity of 3:3 fb-1 by the CMS experiment. It presents the interpretation of the results under spin-0 and spin-2 hypotheses with a relative width up to 5:6 × 10-2 in a mass region of 500 - 4500 GeV. The results of the √s = 13 TeV analysis are combined statistically with previous searches performed by the CMS collaboration, employing a center-of-mass energy of √s = 8 TeV and an integrated luminosity of 19:7 fb-1.

Exposing the QCD Splitting Function with CMS Open Data.

PubMed

Larkoski, Andrew; Marzani, Simone; Thaler, Jesse; Tripathee, Aashish; Xue, Wei

2017-09-29

The splitting function is a universal property of quantum chromodynamics (QCD) which describes how energy is shared between partons. Despite its ubiquitous appearance in many QCD calculations, the splitting function cannot be measured directly, since it always appears multiplied by a collinear singularity factor. Recently, however, a new jet substructure observable was introduced which asymptotes to the splitting function for sufficiently high jet energies. This provides a way to expose the splitting function through jet substructure measurements at the Large Hadron Collider. In this Letter, we use public data released by the CMS experiment to study the two-prong substructure of jets and test the 1→2 splitting function of QCD. To our knowledge, this is the first ever physics analysis based on the CMS Open Data.

Piscine myocarditis virus (PMCV) in wild Atlantic salmon Salmo salar.

PubMed

Garseth, Ase Helen; Biering, Eirik; Tengs, Torstein

2012-12-27

Cardiomyopathy syndrome (CMS) is a severe cardiac disease of sea-farmed Atlantic salmon Salmo salar L., but CMS-like lesions have also been found in wild Atlantic salmon. In 2010 a double-stranded RNA virus of the Totiviridae family, provisionally named piscine myocarditis virus (PMCV), was described as the causative agent of CMS. In the present paper we report the first detection of PMCV in wild Atlantic salmon. The study is based on screening of 797 wild Atlantic salmon by real-time RT-PCR. The samples were collected from 35 different rivers along the coast of Norway, and all individuals included in the study were classified as wild, based on visual appearance and scale reading. Two samples tested positive during PCR analysis, and the results were confirmed by sequencing.

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.

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

NASA Astrophysics Data System (ADS)

Civitarese, Osvaldo; Suhonen, Jouni; Zuber, Kai

2016-10-01

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

Content analysis of CMS Healthcare Innovation Awards from a physiatric perspective.

PubMed

Smith, Matthew J

2014-11-01

On June 15, 2012, the Centers for Medicare and Medicaid Services (CMS) announced the 107 recipients of the Healthcare Innovation Awards (HCIA). The 107 awardees received a total of $874,074,900 in funding, with a projected 3-year savings of $1,863,119,104. A word frequency calculator was used to perform a content analysis on the document that announced the projects receiving funding in the 2012 HCIA program. Results were tabulated and categorized to look for prevailing themes and trends. The words generated by the word frequency calculator were grouped into common roots and tabulated to better understand how CMS was rewarding value. Some of the most common words were "manage," "community," "coordinate," "team," "system" and "integrate." Additionally, the job positions that the projects propose to create were tabulated and grouped into categories. Physicians, including physiatrists, were not often mentioned, whereas nursing and nonclinical positions were frequently listed. This content analysis showed that the concepts emphasized in the HCIA projects parallel fundamental physiatric principles. The findings may help physiatrists understand how reform is unfolding, prepare for the evolving health care landscape, and recognize future opportunities. Copyright © 2014. Published by Elsevier Inc.

[Preliminary proteomics analysis of the total proteins of HL Type cytoplasmic male sterility rice anther].

PubMed

Wen, Li; Liu, Gai; Zhang, Zai-Jun; Tao, Jun; Wan, Cui-Xiang; Zhu, Ying-Guo

2006-03-01

The proteins of HL type cytoplasmic male sterility rice anther of YTA (CMS) and YTB (maintenance line) were separated by two-dimensional electrophoresis with immobilized ph (3-10 non-linear) gradients as the first dimension and SDS-PAGE as the second. The silver-stained proteins spots were analyzed using Image Master 2D software, there were about 1800 detectable spots on each 2D-gel, and about 85 spots were differential expressed. With direct MALDI-TOF mass spectrometry analysis and protein database searching, 9 protein spots out of 16 were identified. Among those proteins, there were Putative nucleic acid binding protein, glucose-1-phosphate adenylyltransferase (ADP-glucose pyrophosphorylase, AGPase) (EC: 2.7.7.27) large chain, UDP-glucuronic acid decarboxylase, putative calcium-binding protein annexin, putative acetyl-CoA synthetase and putative lipoamide dehydrogenase etc. They were closely associated with metabolism, protein biosynthesis, transcription, signal transduction and so on, all of which are cell activities that are essential to pollen development. Some of the identified proteins, i.e. AGPase, putative lipoamide dehydrogenase and putative acetyl-CoA synthetase were deeply discussed on the relationship to CMS. AGPase catalyzes a very important step in the biosynthesis of alpha 1,4-glucans (glycogen or starch) in bacteria and plants: synthesis of the activated glucosyl donor, ADP-glucose, from glucose-1-phosphate and ATP. The lack of the AGPase in male sterile line might directly result in the reduction of starch, and the synthesis of starch was the most important processes during the development of pollen. In present research, the descent or reduction of putative lipoamide dehydrogenase and putative acetyl-CoA synthetase seemed involved in pollen sterility in rice. The degeneration and formation of various tissues during pollen development may impose high demands for energy and key biosynthetic intermediates. Under such conditions, the TCA cycle needs to operate fully, because the TCA cycle is an important source for many intermediates required for biosynthetic pathways, in addition to performing an oxidative, energy-producing role. Thus, it seemed reasonable to infer that the decrease of putative lipoamide dehydrogenase and putative acetyl-CoA synthetase in anther might prevent the conversion of pyruvate into acetyl-CoA, and as a result, the TCA cycle could no longer operate at a sufficient rate to meet all requirements in anther cells, leading to pollen sterility. This study gave new insights into the mechanism of CMS in rice and demonstrated the power of the proteomic approach in plant biology studies.

Exploiting volatile opportunistic computing resources with Lobster

NASA Astrophysics Data System (ADS)

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

2015-12-01

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

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.

Structured feedback on students' concept maps: the proverbial path to learning?

PubMed

Joseph, Conran; Conradsson, David; Nilsson Wikmar, Lena; Rowe, Michael

2017-05-25

Good conceptual knowledge is an essential requirement for health professions students, in that they are required to apply concepts learned in the classroom to a variety of different contexts. However, the use of traditional methods of assessment limits the educator's ability to correct students' conceptual knowledge prior to altering the educational context. Concept mapping (CM) is an educational tool for evaluating conceptual knowledge, but little is known about its use in facilitating the development of richer knowledge frameworks. In addition, structured feedback has the potential to develop good conceptual knowledge. The purpose of this study was to use Kinchin's criteria to assess the impact of structured feedback on the graphical complexity of CM's by observing the development of richer knowledge frameworks. Fifty-eight physiotherapy students created CM's targeting the integration of two knowledge domains within a case-based teaching paradigm. Each student received one round of structured feedback that addressed correction, reinforcement, forensic diagnosis, benchmarking, and longitudinal development on their CM's prior to the final submission. The concept maps were categorized according to Kinchin's criteria as either Spoke, Chain or Net representations, and then evaluated against defined traits of meaningful learning. The inter-rater reliability of categorizing CM's was good. Pre-feedback CM's were predominantly Chain structures (57%), with Net structures appearing least often. There was a significant reduction of the basic Spoke- structured CMs (P = 0.002) and a significant increase of Net-structured maps (P < 0.001) at the final evaluation (post-feedback). Changes in structural complexity of CMs appeared to be indicative of broader knowledge frameworks as assessed against the meaningful learning traits. Feedback on CM's seemed to have contributed towards improving conceptual knowledge and correcting naive conceptions of related knowledge. Educators in medical education could therefore consider using CM's to target individual student development.

Congenital Myasthenic Syndrome Type 19 Is Caused by Mutations in COL13A1, Encoding the Atypical Non-fibrillar Collagen Type XIII α1 Chain.

PubMed

Logan, Clare V; Cossins, Judith; Rodríguez Cruz, Pedro M; Parry, David A; Maxwell, Susan; Martínez-Martínez, Pilar; Riepsaame, Joey; Abdelhamed, Zakia A; Lake, Alice V R; Moran, Maria; Robb, Stephanie; Chow, Gabriel; Sewry, Caroline; Hopkins, Philip M; Sheridan, Eamonn; Jayawant, Sandeep; Palace, Jacqueline; Johnson, Colin A; Beeson, David

2015-12-03

The neuromuscular junction (NMJ) consists of a tripartite synapse with a presynaptic nerve terminal, Schwann cells that ensheathe the terminal bouton, and a highly specialized postsynaptic membrane. Synaptic structural integrity is crucial for efficient signal transmission. Congenital myasthenic syndromes (CMSs) are a heterogeneous group of inherited disorders that result from impaired neuromuscular transmission, caused by mutations in genes encoding proteins that are involved in synaptic transmission and in forming and maintaining the structural integrity of NMJs. To identify further causes of CMSs, we performed whole-exome sequencing (WES) in families without an identified mutation in known CMS-associated genes. In two families affected by a previously undefined CMS, we identified homozygous loss-of-function mutations in COL13A1, which encodes the alpha chain of an atypical non-fibrillar collagen with a single transmembrane domain. COL13A1 localized to the human muscle motor endplate. Using CRISPR-Cas9 genome editing, modeling of the COL13A1 c.1171delG (p.Leu392Sfs(∗)71) frameshift mutation in the C2C12 cell line reduced acetylcholine receptor (AChR) clustering during myotube differentiation. This highlights the crucial role of collagen XIII in the formation and maintenance of the NMJ. Our results therefore delineate a myasthenic disorder that is caused by loss-of-function mutations in COL13A1, encoding a protein involved in organization of the NMJ, and emphasize the importance of appropriate symptomatic treatment for these individuals. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2018-05-18

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

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.

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.

Thermal diffusivity of alpha-mercuric iodide

NASA Astrophysics Data System (ADS)

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

1991-01-01

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

Experimental High Energy Physics Research

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

Hohlmann, Marcus

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

Candidate Reference Genes Selection and Application for RT-qPCR Analysis in Kenaf with Cytoplasmic Male Sterility Background

PubMed Central

Zhou, Bujin; Chen, Peng; Khan, Aziz; Zhao, Yanhong; Chen, Lihong; Liu, Dongmei; Liao, Xiaofang; Kong, Xiangjun; Zhou, Ruiyang

2017-01-01

Cytoplasmic male sterility (CMS) is a maternally inherited trait that results in the production of dysfunctional pollen. Based on reliable reference gene-normalized real-time quantitative PCR (RT-qPCR) data, examining gene expression profile can provide valuable information on the molecular mechanism of kenaf CMS. However, studies have not been conducted regarding selection of reference genes for normalizing RT-qPCR data in the CMS and maintainer lines of kenaf crop. Therefore, we studied 10 candidate reference genes (ACT3, ELF1A, G6PD, PEPKR1, TUB, TUA, CYP, GAPDH, H3, and 18S) to assess their expression stability at three stages of pollen development in CMS line 722A and maintainer line 722B of kenaf. Five computational statistical approaches (GeNorm, NormFinder, ΔCt, BestKeeper, and RefFinder) were used to evaluate the expression stability levels of these genes. According to RefFinder and GeNorm, the combination of TUB, CYP, and PEPKR1 was identified as an internal control for the accurate normalization across all sample set, which was further confirmed by validating the expression of HcPDIL5-2a. Furthermore, the combination of TUB, CYP, and PEPKR1 was used to differentiate the expression pattern of five mitochondria F1F0-ATPase subunit genes (atp1, atp4, atp6, atp8, and atp9) by RT-qPCR during pollen development in CMS line 722A and maintainer line 722B. We found that atp1, atp6, and atp9 exhibited significantly different expression patterns during pollen development in line 722A compared with line 722B. This is the first systematic study of reference genes selection for CMS and will provide useful information for future research on the gene expressions and molecular mechanisms underlying CMS in kenaf. PMID:28919905

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.

An overview of the DII-HEP OpenStack based CMS data analysis

NASA Astrophysics Data System (ADS)

Osmani, L.; Tarkoma, S.; Eerola, P.; Komu, M.; Kortelainen, M. J.; Kraemer, O.; Lindén, T.; Toor, S.; White, J.

2015-05-01

An OpenStack based private cloud with the Cluster File System has been built and used with both CMS analysis and Monte Carlo simulation jobs in the Datacenter Indirection Infrastructure for Secure High Energy Physics (DII-HEP) project. On the cloud we run the ARC middleware that allows running CMS applications without changes on the job submission side. Our test results indicate that the adopted approach provides a scalable and resilient solution for managing resources without compromising on performance and high availability. To manage the virtual machines (VM) dynamically in an elastic fasion, we are testing the EMI authorization service (Argus) and the Execution Environment Service (Argus-EES). An OpenStackplugin has been developed for Argus-EES. The Host Identity Protocol (HIP) has been designed for mobile networks and it provides a secure method for IP multihoming. HIP separates the end-point identifier and locator role for IP address which increases the network availability for the applications. Our solution leverages HIP for traffic management. This presentation gives an update on the status of the work and our lessons learned in creating an OpenStackbased cloud for HEP.

A new source of cytoplasmic male sterility in pearl millet: RFLP analysis of mitochondrial DNA.

PubMed

Sujata, V; Sivaramakrishnan, S; Rai, K N; Seetha, K

1994-06-01

A new source of cytoplasmic male sterility (cms) in pearl millet (Pennisetum glaucum (L.) R.Br.) derived from a half-sib progeny of the Early Gene Pool (EGP 261) and used in a male-sterile line, ICMA 90111, was compared with other known cms sources for RFLP of mitochondrial (mt) DNA. Southern blot hybridization of mtDNA from ICMA 90111 digested with several restriction enzymes and probed with homologous mtDNA clones from pearl millet and heterologous gene clones from maize and wheat revealed the RFLP patterns of ICMA 90111 distinct from others studied so far. The dendrogram of male-sterile lines constructed from the Southern blot hybridization patterns indicated that ICMA 90111 represents a separate group. Our results suggest that this source of cms is unique in several respects.

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.

Development and validation of the Overlap Muon Track Finder for the CMS experiment

NASA Astrophysics Data System (ADS)

Dobosz, J.; Mietki, P.; Zawistowski, K.; Żarnecki, G.

2016-09-01

Present article is a description of the authors contribution in upgrade and analysis of performance of the Level-1 Muon Trigger of the CMS experiment. The authors are students of University of Warsaw and Gdansk University of Technology. They are collaborating with the CMS Warsaw Group. This article summarises students' work presented during the Students session during the Workshop XXXVIII-th IEEE-SPIE Joint Symposium Wilga 2016. In the first section the CMS experiment is briefly described and the importance of the trigger system is explained. There is also shown basic difference between old muon trigger strategy and the upgraded one. The second section is devoted to Overlap Muon Track Finder (OMTF). This is one of the crucial components of the Level-1 Muon Trigger. The algorithm of OMTF is described. In the third section there is discussed one of the event selection aspects - cut on the muon transverse momentum pT . Sometimes physical muon with pT bigger than a certain threshold is unnecessarily cut and physical muon with lower pT survives. To improve pT selection modified algorithm was proposed and its performance was studied. One of the features of the OMTF is that one physical muon often results in several muon candidates. The Ghost-Buster algorithm is designed to eliminate surplus candidates. In the fourth section this algorithm and its performance on different data samples are discussed. In the fifth section Local Data Acquisition System (Local DAQ) is briefly described. It supports initial system commissioning. The test done with OMTF Local DAQ are described. In the sixth section there is described development of web application used for the control and monitoring of CMS electronics. The application provides access to graphical user interface for manual control and the connection to the CMS hierarchical Run Control.

Elastic Extension of a CMS Computing Centre Resources on External Clouds

NASA Astrophysics Data System (ADS)

Codispoti, G.; Di Maria, R.; Aiftimiei, C.; Bonacorsi, D.; Calligola, P.; Ciaschini, V.; Costantini, A.; Dal Pra, S.; DeGirolamo, D.; Grandi, C.; Michelotto, D.; Panella, M.; Peco, G.; Sapunenko, V.; Sgaravatto, M.; Taneja, S.; Zizzi, G.

2016-10-01

After the successful LHC data taking in Run-I and in view of the future runs, the LHC experiments are facing new challenges in the design and operation of the computing facilities. The computing infrastructure for Run-II is dimensioned to cope at most with the average amount of data recorded. The usage peaks, as already observed in Run-I, may however originate large backlogs, thus delaying the completion of the data reconstruction and ultimately the data availability for physics analysis. In order to cope with the production peaks, CMS - along the lines followed by other LHC experiments - is exploring the opportunity to access Cloud resources provided by external partners or commercial providers. Specific use cases have already been explored and successfully exploited during Long Shutdown 1 (LS1) and the first part of Run 2. In this work we present the proof of concept of the elastic extension of a CMS site, specifically the Bologna Tier-3, on an external OpenStack infrastructure. We focus on the “Cloud Bursting” of a CMS Grid site using a newly designed LSF configuration that allows the dynamic registration of new worker nodes to LSF. In this approach, the dynamically added worker nodes instantiated on the OpenStack infrastructure are transparently accessed by the LHC Grid tools and at the same time they serve as an extension of the farm for the local usage. The amount of resources allocated thus can be elastically modeled to cope up with the needs of CMS experiment and local users. Moreover, a direct access/integration of OpenStack resources to the CMS workload management system is explored. In this paper we present this approach, we report on the performances of the on-demand allocated resources, and we discuss the lessons learned and the next steps.

Vaccination with vascular progenitor cells derived from induced pluripotent stem cells elicits antitumor immunity targeting vascular and tumor cells.

PubMed

Koido, Shigeo; Ito, Masaki; Sagawa, Yukiko; Okamoto, Masato; Hayashi, Kazumi; Nagasaki, Eijiro; Kan, Shin; Komita, Hideo; Kamata, Yuko; Homma, Sadamu

2014-05-01

Vaccination of BALB/c mice with dendritic cells (DCs) loaded with the lysate of induced vascular progenitor (iVP) cells derived from murine-induced pluripotent stem (iPS) cells significantly suppressed the tumor of CMS-4 fibrosarcomas and prolonged the survival of CMS-4-inoculated mice. This prophylactic antitumor activity was more potent than that of immunization with DCs loaded with iPS cells or CMS-4 tumor cells. Tumors developed slowly in mice vaccinated with DCs loaded with iVP cells (DC/iVP) and exhibited a limited vascular bed. Immunohistochemistry and a tomato-lectin perfusion study demonstrated that the tumors that developed in the iVP-immunized mice showed a marked decrease in tumor vasculature. Immunization with DC/iVP induced a potent suppressive effect on vascular-rich CMS-4 tumors, a weaker effect on BNL tumors with moderate vasculature, and nearly no effect on C26 tumors with poor vasculature. Treatment of DC/iVP-immunized mice with a monoclonal antibody against CD4 or CD8, but not anti-asialo GM1, inhibited the antitumor activity. CD8(+) T cells from DC/iVP-vaccinated mice showed significant cytotoxic activity against murine endothelial cells and CMS-4 cells, whereas CD8(+) T cells from DC/iPS-vaccinated mice did not. DNA microarray analysis showed that the products of 29 vasculature-associated genes shared between genes upregulated by differentiation from iPS cells into iVP cells and genes shared by iVP cells and isolated Flk-1(+) vascular cells in CMS-4 tumor tissue might be possible targets in the immune response. These results suggest that iVP cells from iPS cells could be used as a cancer vaccine targeting tumor vascular cells and tumor cells.

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

PubMed

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

2014-09-05

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

Impaired coronary flow reserve in patients with metabolic syndrome.

PubMed

Pirat, Bahar; Bozbas, Huseyin; Simsek, Vahide; Yildirir, Aylin; Sade, L Elif; Gursoy, Yusuf; Altin, Cihan; Atar, Ilyas; Muderrisoglu, Haldun

2008-11-01

Metabolic syndrome (MetS) is a strong predictor of cardiovascular events. Coronary flow reserve (CFR), as determined by transthoracic echocardiography, is an indicator of microvascular function. In this study, we sought to determine whether CFR is impaired in patients with MetS without clinical coronary heart disease. Thirty-three patients with MetS (mean age, 67+/-8 years) and 35 age- and sex-matched controls were studied prospectively. Transthoracic two-dimensional and Doppler echocardiography was performed on all patients. Baseline and hyperemic (after dipyridamole infusion) coronary flow rates were measured using pulsed Doppler echocardiography. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocities. There was no difference with regard to baseline systolic and diastolic coronary flow rates in patients with MetS compared with control subjects (19.9+/-3.1cm/s vs. 19.7+/-2.9cm/s, P>.05; and 27.7+/-4.2cm/s vs. 27.1+/-3.6cm/s, P>.05, respectively). Hyperemic diastolic flow and CFR were significantly lower in patients with MetS than in controls (61.7+/-9.4cm/s vs. 70.2+/-9.2cm/s, P<.0001; and 2.2+/-0.5 vs. 2.6+/-0.4, P=.001, respectively). In a logistic regression analysis that included age, sex, body mass index, hypertension, and dyslipidemia and MetS, MetS was the only predictor of a CFR<2.5 (P=.007, OR=6.1, 95% CI: 1.6-23.3). In conclusion, CFR is impaired in patients with MetS suggesting that coronary microvascular dysfunction, an early finding of atherosclerosis, is present in this patient population. Metabolic syndrome is associated with a CFR<2.5.

Influence of flow velocity on motor behavior of sea cucumber Apostichopus japonicus.

PubMed

Pan, Yang; Zhang, Libin; Lin, Chenggang; Sun, Jiamin; Kan, Rentao; Yang, Hongsheng

2015-05-15

The influence of flow velocity on the motor behavior of the sea cucumber, Apostichopus japonicus was investigated in the laboratory. Cameras were used to record sea cucumber movements and behavior analysis software was used to measure the distance traveled, time spent, upstream or downstream of the start position and the speed of movements. In general, the mean velocity of A. japonicus was below 0.7mms(-1). The maximum velocity recorded for all the sea cucumbers tested was for a large individual (89.25±17.11g), at a flow rate of 4.6±0.5cms(-1). Medium sized (19.68±5.53g) and large individuals moved significantly faster than small individuals (2.65±1.24g) at the same flow rate. A. japonicus moved significantly faster when there was a moderate current (4.6±0.5cms(-1) and 14.7±0.3cms(-1)), compared with the fast flow rate (29.3±3.7cms(-1)) and when there was no flow (0cms(-1)). Sea cucumbers did not show positive rheotaxis in general, but did move in a downstream direction at faster current speeds. Large, medium and small sized individuals moved downstream at the fastest current speed tested, 29.3±3.7cms(-1). When there was no water flow, sea cucumbers tended to move in an irregular pattern. The movement patterns show that the sea cucumber, A. japonicus can move across the direction of flow, and can move both upstream and downstream along the direction of flow. Copyright © 2015. Published by Elsevier Inc.

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

PubMed

El-Sheikh, Manal A

2016-11-05

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

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

PubMed Central

2010-01-01

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

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

PubMed Central

Reddemann, Antje; Horn, Renate

2018-01-01

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

Searches for anomalous coupling in top-quark interaction with the W boson and b quark, along with searches for quark-flavor-changing neutral currents, in an analysis of data from the CMS experiment

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

Boos, E. E.; Bunichev, V. E.; Vorotnikov, G. A.

2016-01-15

The results of searches for effects beyond the Standard Model in processes of single top-quark production in the CMS experiment are presented. Anomalous contributions of the vector and magnetic types in top-quark interaction with the W boson and b quark and quark-flavor-changing neutral currents in top-quark interaction with the c or u quark via gluon exchange were studied. The respective analysis was performed with the aid of Bayesian neural networks. No statistically significant deviations were found, and upper limits on anomalous couplings at a 95% confidence level were set.

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.

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...

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...

Intermittent Oxygen Inhalation with Proper Frequency Improves Overall Health Conditions and Alleviates Symptoms in a Population at High Risk of Chronic Mountain Sickness with Severe Symptoms

PubMed Central

Feng, Bin; Xu, Wei-Hao; Gao, Yu-Qi; Liu, Fu-Yu; Li, Peng; Zheng, Shan-Jun; Gai, Lu-Yue; Zhang, Gang

2016-01-01

Background: Oxygen inhalation therapy is essential for the treatment of patients with chronic mountain sickness (CMS), but the efficacy of oxygen inhalation for populations at high risk of CMS remains unknown. This research investigated whether oxygen inhalation therapy benefits populations at high risk of CMS. Methods: A total of 296 local residents living at an altitude of 3658 m were included; of which these were 25 diagnosed cases of CMS, 8 cases dropped out of the study, and 263 cases were included in the analysis. The subjects were divided into high-risk (180 ≤ hemoglobin (Hb) <210 g/L, n = 161) and low-risk (Hb <180 g/L, n = 102) groups, and the cases in each group were divided into severe symptom (CMS score ≥6) and mild symptom (CMS score 0-5) subgroups. Severe symptomatic population of either high- or low-risk CMS was randomly assigned to no oxygen intake group (A group) or oxygen intake 7 times/week group (D group); mild symptomatic population of either high- or low-risk CMS was randomly assigned to no oxygen intake group (A group), oxygen intake 2 times/week group (B group), and 4 times/week group (C group). The courses for oxygen intake were all 30 days. The CMS symptoms, sleep quality, physiological biomarkers, biochemical markers, etc., were recorded on the day before oxygen intake, on the 15th and 30th days of oxygen intake, and on the 15th day after terminating oxygen intake therapy. Results: A total of 263 residents were finally included in the analysis. Among these high-altitude residents, CMS symptom scores decreased for oxygen inhalation methods B, C, and D at 15 and 30 days after oxygen intake and 15 days after termination, including dyspnea, palpitation, and headache index, compared to those before oxygen intake (B group: Z = 5.604, 5.092, 5.741; C group: Z = 4.155, 4.068, 4.809; D group: Z = 6.021, 6.196, 5.331, at the 3 time points respectively; all P < 0.05/3 vs. before intake). However, dyspnea/palpitation (A group: Z = 5.003, 5.428, 5.493, both P < 0.05/3 vs. before intake) and headache (A group: Z = 4.263, 3.890, 4.040, both P < 0.05/3 vs. before intake) index decreased significantly also for oxygen inhalation method A at all the 3 time points. Cyanosis index decreased significantly 30 days after oxygen intake only in the group of participants administered the D method (Z = 2.701, P = 0.007). Tinnitus index decreased significantly in group A and D at 15 days (A group: Z = 3.377, P = 0.001, D group: Z = 3.150, P = 0.002), 30 days after oxygen intake (A group: Z = 2.836, P = 0.005, D group: Z = 5.963, P < 0.0001) and 15 days after termination (A group: Z = 2.734, P = 0.006, D group: Z = 4.049, P = 0.0001), and decreased significantly in the group B and C at 15 days after termination (B group: Z = 2.611, P = 0.009; C group: Z = 3.302, P = 0.001). In the population at high risk of CMS with severe symptoms, oxygen intake 7 times/week significantly improved total symptom scores of severe symptoms at 15 days (4 [2, 5] vs. 5.5 [4, 7], Z = 2.890, P = 0.005) and 30 days (3 [1, 5] vs. 5.5 [2, 7], Z = 3.270, P = 0.001) after oxygen intake compared to no oxygen intake. In the population at high risk of CMS with mild symptoms, compared to no oxygen intake, oxygen intake 2 or 4 times/week did not improve the total symptom scores at 15 days (2 [1, 3], 3 [1, 4] vs. 3 [1.5, 5]; χ2= 2.490, P = 0.288), and at 30 days (2 [0, 4], 2 [1, 4.5] vs. 3 [2, 5]; χ2= 3.730, P = 0.155) after oxygen intake. In the population at low risk of CMS, oxygen intake did not significantly change the white cell count and red cell count compared to no oxygen intake, neither in the severe symptomatic population nor in the mild symptomatic population. Conclusions: Intermittent oxygen inhalation with proper frequency might alleviate symptoms in residents at high altitude by improving their overall health conditions. Administration of oxygen inhalation therapy 2–4 times/week might not benefit populations at high risk of CMS with mild CMS symptoms while administration of therapy 7 times/week might benefit those with severe symptoms. Oxygen inhalation therapy is not recommended for low-risk CMS populations. PMID:27231170

The spectrum of mutations that underlie the neuromuscular junction synaptopathy in DOK7 congenital myasthenic syndrome.

PubMed

Cossins, Judith; Liu, Wei Wei; Belaya, Katsiaryna; Maxwell, Susan; Oldridge, Michael; Lester, Tracy; Robb, Stephanie; Beeson, David

2012-09-01

Congenital myasthenic syndromes (CMS) are a group of inherited diseases that affect synaptic transmission at the neuromuscular junction and result in fatiguable muscle weakness. A subgroup of CMS patients have a recessively inherited limb-girdle pattern of weakness caused by mutations in DOK7. DOK7 encodes DOK7, an adaptor protein that is expressed in the skeletal muscle and heart and that is essential for the development and maintenance of the neuromuscular junction. We have screened the DOK7 gene for mutations by polymerase chain reaction amplification and bi-directional sequencing of exonic and promoter regions and performed acetylcholine receptor (AChR) clustering assays and used exon trapping to determine the pathogenicity of detected variants. Approximately 18% of genetically diagnosed CMSs in the UK have mutations in DOK7, with mutations in this gene identified in more than 60 kinships to date. Thirty-four different pathogenic mutations were identified as well as 27 variants likely to be non-pathogenic. An exon 7 frameshift duplication c.1124_1127dupTGCC is commonly found in at least one allele. We analyse the effect of the common frameshift c.1124_1127dupTGCC and show that 10/11 suspected missense mutations have a deleterious effect on AChR clustering. We identify for the first time homozygous or compound heterozygous mutations that are localized 5' to exon 7. In addition, three silent variants in the N-terminal half of DOK7 are predicted to alter the splicing of the DOK7 RNA transcript. The DOK7 gene is highly polymorphic, and within these many variants, we define a spectrum of mutations that can underlie DOK7 CMS that will inform in managing this disorder.

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

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.

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.

Grid site availability evaluation and monitoring at CMS

DOE PAGES

Lyons, Gaston; Maciulaitis, Rokas; Bagliesi, Giuseppe; ...

2017-10-01

The Compact Muon Solenoid (CMS) experiment at the Large Hadron Collider (LHC) uses distributed grid computing to store, process, and analyse the vast quantity of scientific data recorded every year. The computing resources are grouped into sites and organized in a tiered structure. Each site provides computing and storage to the CMS computing grid. Over a hundred sites worldwide contribute with resources from hundred to well over ten thousand computing cores and storage from tens of TBytes to tens of PBytes. In such a large computing setup scheduled and unscheduled outages occur continually and are not allowed to significantly impactmore » data handling, processing, and analysis. Unscheduled capacity and performance reductions need to be detected promptly and corrected. CMS developed a sophisticated site evaluation and monitoring system for Run 1 of the LHC based on tools of the Worldwide LHC Computing Grid. For Run 2 of the LHC the site evaluation and monitoring system is being overhauled to enable faster detection/reaction to failures and a more dynamic handling of computing resources. Furthermore, enhancements to better distinguish site from central service issues and to make evaluations more transparent and informative to site support staff are planned.« less

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.

Grid site availability evaluation and monitoring at CMS

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

Lyons, Gaston; Maciulaitis, Rokas; Bagliesi, Giuseppe

The Compact Muon Solenoid (CMS) experiment at the Large Hadron Collider (LHC) uses distributed grid computing to store, process, and analyse the vast quantity of scientific data recorded every year. The computing resources are grouped into sites and organized in a tiered structure. Each site provides computing and storage to the CMS computing grid. Over a hundred sites worldwide contribute with resources from hundred to well over ten thousand computing cores and storage from tens of TBytes to tens of PBytes. In such a large computing setup scheduled and unscheduled outages occur continually and are not allowed to significantly impactmore » data handling, processing, and analysis. Unscheduled capacity and performance reductions need to be detected promptly and corrected. CMS developed a sophisticated site evaluation and monitoring system for Run 1 of the LHC based on tools of the Worldwide LHC Computing Grid. For Run 2 of the LHC the site evaluation and monitoring system is being overhauled to enable faster detection/reaction to failures and a more dynamic handling of computing resources. Furthermore, enhancements to better distinguish site from central service issues and to make evaluations more transparent and informative to site support staff are planned.« less

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.

Grid site availability evaluation and monitoring at CMS

NASA Astrophysics Data System (ADS)

Lyons, Gaston; Maciulaitis, Rokas; Bagliesi, Giuseppe; Lammel, Stephan; Sciabà, Andrea

2017-10-01

The Compact Muon Solenoid (CMS) experiment at the Large Hadron Collider (LHC) uses distributed grid computing to store, process, and analyse the vast quantity of scientific data recorded every year. The computing resources are grouped into sites and organized in a tiered structure. Each site provides computing and storage to the CMS computing grid. Over a hundred sites worldwide contribute with resources from hundred to well over ten thousand computing cores and storage from tens of TBytes to tens of PBytes. In such a large computing setup scheduled and unscheduled outages occur continually and are not allowed to significantly impact data handling, processing, and analysis. Unscheduled capacity and performance reductions need to be detected promptly and corrected. CMS developed a sophisticated site evaluation and monitoring system for Run 1 of the LHC based on tools of the Worldwide LHC Computing Grid. For Run 2 of the LHC the site evaluation and monitoring system is being overhauled to enable faster detection/reaction to failures and a more dynamic handling of computing resources. Enhancements to better distinguish site from central service issues and to make evaluations more transparent and informative to site support staff are planned.

Use of DAGMan in CRAB3 to Improve the Splitting of CMS User Jobs

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

Wolf, M.; Mascheroni, M.; Woodard, A.

CRAB3 is a workload management tool used by CMS physicists to analyze data acquired by the Compact Muon Solenoid (CMS) detector at the CERN Large Hadron Collider (LHC). Research in high energy physics often requires the analysis of large collections of files, referred to as datasets. The task is divided into jobs that are distributed among a large collection of worker nodes throughout the Worldwide LHC Computing Grid (WLCG). Splitting a large analysis task into optimally sized jobs is critical to efficient use of distributed computing resources. Jobs that are too big will have excessive runtimes and will not distributemore » the work across all of the available nodes. However, splitting the project into a large number of very small jobs is also inefficient, as each job creates additional overhead which increases load on infrastructure resources. Currently this splitting is done manually, using parameters provided by the user. However the resources needed for each job are difficult to predict because of frequent variations in the performance of the user code and the content of the input dataset. As a result, dividing a task into jobs by hand is difficult and often suboptimal. In this work we present a new feature called “automatic splitting” which removes the need for users to manually specify job splitting parameters. We discuss how HTCondor DAGMan can be used to build dynamic Directed Acyclic Graphs (DAGs) to optimize the performance of large CMS analysis jobs on the Grid. We use DAGMan to dynamically generate interconnected DAGs that estimate the processing time the user code will require to analyze each event. This is used to calculate an estimate of the total processing time per job, and a set of analysis jobs are run using this estimate as a specified time limit. Some jobs may not finish within the alloted time; they are terminated at the time limit, and the unfinished data is regrouped into smaller jobs and resubmitted.« less

Influence of the South-to-North Water Transfer and the Yangtze River Mitigation Projects on the water quality of Han River, China

NASA Astrophysics Data System (ADS)

Liu, W.; Kuo, Y. M.

2016-12-01

The Middle Route of China's South-to-North Water Transfer (MSNW) and Yangtze-Han River Water Diversion (YHWD) Projects have been operated since 2014, which may deteriorate water quality in Han River. The 11 water sampling sites distributed from the middle and down streams of Han River watershed were monitored monthly between July 2014 and December 2015. Factor analysis and cluster analysis were applied to investigate the major pollution types and main variables influencing water quality in Han River. The factor analysis distinguishes three main pollution types (agricultural nonpoint source, organic, and phosphorus point source pollution) affecting water quality of Han River. Cluster analysis classified all sampling sites into four groups and determined their pollution source for both Dry and Wet seasons. The sites located at central city receive point source pollution in both seasons. The water quality in downstream Han River (excluding central city sites) was influenced by nonpoint source pollution from Jianghan Plain. Variations of water qualities are associated with hydrological conditions varied from operations of engineering projects and seasonal variability especially in Dry season. Good water quality as Class III mainly occurred when flow rate is greater than 800 cms in Dry season. The low average flow rate below 583 cms will degrade water quality as Class V at almost all sites. Elevating the flow rate discharged from MSNW and YHWD Projects to Han River can avoid degrading water quality especially in low flow conditions and may decrease the probability of algal bloom occurrence in Han River. Increasing the flow rate from 400 cms to 700 cms in main Han River can obviously improve the water quality of Han River. The investigation of relationships between water quality and flow rate in both projects can provide management strategies of water quality for various flow conditions.

Use of DAGMan in CRAB3 to improve the splitting of CMS user jobs

NASA Astrophysics Data System (ADS)

Wolf, M.; Mascheroni, M.; Woodard, A.; Belforte, S.; Bockelman, B.; Hernandez, J. M.; Vaandering, E.

2017-10-01

CRAB3 is a workload management tool used by CMS physicists to analyze data acquired by the Compact Muon Solenoid (CMS) detector at the CERN Large Hadron Collider (LHC). Research in high energy physics often requires the analysis of large collections of files, referred to as datasets. The task is divided into jobs that are distributed among a large collection of worker nodes throughout the Worldwide LHC Computing Grid (WLCG). Splitting a large analysis task into optimally sized jobs is critical to efficient use of distributed computing resources. Jobs that are too big will have excessive runtimes and will not distribute the work across all of the available nodes. However, splitting the project into a large number of very small jobs is also inefficient, as each job creates additional overhead which increases load on infrastructure resources. Currently this splitting is done manually, using parameters provided by the user. However the resources needed for each job are difficult to predict because of frequent variations in the performance of the user code and the content of the input dataset. As a result, dividing a task into jobs by hand is difficult and often suboptimal. In this work we present a new feature called “automatic splitting” which removes the need for users to manually specify job splitting parameters. We discuss how HTCondor DAGMan can be used to build dynamic Directed Acyclic Graphs (DAGs) to optimize the performance of large CMS analysis jobs on the Grid. We use DAGMan to dynamically generate interconnected DAGs that estimate the processing time the user code will require to analyze each event. This is used to calculate an estimate of the total processing time per job, and a set of analysis jobs are run using this estimate as a specified time limit. Some jobs may not finish within the alloted time; they are terminated at the time limit, and the unfinished data is regrouped into smaller jobs and resubmitted.

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.

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

PubMed

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

1999-12-01

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

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...

The complications and the position of the Codman MicroSensor™ ICP device: an analysis of 549 patients and 650 Sensors.

PubMed

Koskinen, Lars-Owe D; Grayson, David; Olivecrona, Magnus

2013-11-01

Complications of and insertion depth of the Codman MicroSensor ICP monitoring device (CMS) is not well studied. To study complications and the insertion depth of the CMS in a clinical setting. We identified all patients who had their intracranial pressure (ICP) monitored using a CMS device between 2002 and 2010. The medical records and post implantation computed tomography (CT) scans were analyzed for occurrence of infection, hemorrhage and insertion depth. In all, 549 patients were monitored using 650 CMS. Mean monitoring time was 7.0 ± 4.9 days. The mean implantation depth was 21.3 ± 11.1 mm (0-88 mm). In 27 of the patients, a haematoma was identified; 26 of these were less than 1 ml, and one was 8 ml. No clinically significant bleeding was found. There was no statistically significant increase in the number of hemorrhages in presumed coagulopathic patients. The infection rate was 0.6 % and the calculated infection rate per 1,000 catheter days was 0.8. The risk for hemorrhagic and infectious complications when using the CMS for ICP monitoring is low. The depth of insertion varies considerably and should be taken into account if patients are treated with head elevation, since the pressure is measured at the tip of the sensor. To meet the need for ICP monitoring, an intraparenchymal ICP monitoring device should be preferred to the use of an external ventricular drainage (EVD).

Inhibition of TGFβ signaling increases direct conversion of fibroblasts to induced cardiomyocytes.

PubMed

Ifkovits, Jamie L; Addis, Russell C; Epstein, Jonathan A; Gearhart, John D

2014-01-01

Recent studies have been successful at utilizing ectopic expression of transcription factors to generate induced cardiomyocytes (iCMs) from fibroblasts, albeit at a low frequency in vitro. This work investigates the influence of small molecules that have been previously reported to improve differentiation to cardiomyocytes as well as reprogramming to iPSCs in conjunction with ectopic expression of the transcription factors Hand2, Nkx2.5, Gata4, Mef2C, and Tbx5 on the conversion to functional iCMs. We utilized a reporter system in which the calcium indicator GCaMP is driven by the cardiac Troponin T promoter to quantify iCM yield. The TGFβ inhibitor, SB431542 (SB), was identified as a small molecule capable of increasing the conversion of both mouse embryonic fibroblasts and adult cardiac fibroblasts to iCMs up to ∼5 fold. Further characterization revealed that inhibition of TGFβ by SB early in the reprogramming process led to the greatest increase in conversion of fibroblasts to iCMs in a dose-responsive manner. Global transcriptional analysis at Day 3 post-induction of the transcription factors revealed an increased expression of genes associated with the development of cardiac muscle in the presence of SB compared to the vehicle control. Incorporation of SB in the reprogramming process increases the efficiency of iCM generation, one of the major goals necessary to enable the use of iCMs for discovery-based applications and for the clinic.

Inhibition of TGFβ Signaling Increases Direct Conversion of Fibroblasts to Induced Cardiomyocytes

PubMed Central

Ifkovits, Jamie L.; Addis, Russell C.; Epstein, Jonathan A.; Gearhart, John D.

2014-01-01

Recent studies have been successful at utilizing ectopic expression of transcription factors to generate induced cardiomyocytes (iCMs) from fibroblasts, albeit at a low frequency in vitro. This work investigates the influence of small molecules that have been previously reported to improve differentiation to cardiomyocytes as well as reprogramming to iPSCs in conjunction with ectopic expression of the transcription factors Hand2, Nkx2.5, Gata4, Mef2C, and Tbx5 on the conversion to functional iCMs. We utilized a reporter system in which the calcium indicator GCaMP is driven by the cardiac Troponin T promoter to quantify iCM yield. The TGFβ inhibitor, SB431542 (SB), was identified as a small molecule capable of increasing the conversion of both mouse embryonic fibroblasts and adult cardiac fibroblasts to iCMs up to ∼5 fold. Further characterization revealed that inhibition of TGFβ by SB early in the reprogramming process led to the greatest increase in conversion of fibroblasts to iCMs in a dose-responsive manner. Global transcriptional analysis at Day 3 post-induction of the transcription factors revealed an increased expression of genes associated with the development of cardiac muscle in the presence of SB compared to the vehicle control. Incorporation of SB in the reprogramming process increases the efficiency of iCM generation, one of the major goals necessary to enable the use of iCMs for discovery-based applications and for the clinic. PMID:24586958

Study design and implementation for population pharmacokinetics of Chinese medicine: An expert consensus.

PubMed

Jiang, Jun-jie; Zhang, Wen; Xie, Yan-ming; Wang, Jian-nong; He, Fu-yuan; Xiong, Xin

2016-02-01

Although many population pharmacokinetics (PPK) researches have been conducted on chemical drugs, few have been in the field of Chinese medicine (CM). Each ingredient in CMs possesses different pharmacokinetic characteristics, therefore, it is important to develop methods of PPK studies on them to identify the differences in CM drug safety and efficacy among the population subgroups and to conduct quantitative studies on the determinants of CM drug concentrations. To develop an expert consensus on study design and implementation for PPK of CM, in August 2013, 6 experts in the field of PPK, CMs pharmacology, and statistics discussed problems on the PPK research protocol of CMs, and a consensus was reached. The medicines with toxicity and narrow therapeutic windows and with wide range of target population or with frequent adverse reactions were selected. The compositions with definite therapeutic effects were selected as indices, and specific time points and sample sizes were designed according to standard PPK design methods. Target components were tested through various chromatography methods. Total quantity statistical moment analysis was used to estimate PPK parameters of each component and PPK models reflecting the trend of CMs (which assists in reasonable adjustments on clinical dosage). This consensus specifies the study design and implementation process of PPK. It provides guidance for the following: post-marketing clinical studies, in vivo investigations related to the metabolism in different populations, and development and clinical adjustment of dosages of CMs.

The Impact of Hospital Size on CMS Hospital Profiling.

PubMed

Sosunov, Eugene A; Egorova, Natalia N; Lin, Hung-Mo; McCardle, Ken; Sharma, Vansh; Gelijns, Annetine C; Moskowitz, Alan J

2016-04-01

The Centers for Medicare & Medicaid Services (CMS) profile hospitals using a set of 30-day risk-standardized mortality and readmission rates as a basis for public reporting. These measures are affected by hospital patient volume, raising concerns about uniformity of standards applied to providers with different volumes. To quantitatively determine whether CMS uniformly profile hospitals that have equal performance levels but different volumes. Retrospective analysis of patient-level and hospital-level data using hierarchical logistic regression models with hospital random effects. Simulation of samples including a subset of hospitals with different volumes but equal poor performance (hospital effects=+3 SD in random-effect logistic model). A total of 1,085,568 Medicare fee-for-service patients undergoing 1,494,993 heart failure admissions in 4930 hospitals between July 1, 2005 and June 30, 2008. CMS methodology was used to determine the rank and proportion (by volume) of hospitals reported to perform "Worse than US National Rate." Percent of hospitals performing "Worse than US National Rate" was ∼40 times higher in the largest (fifth quintile by volume) compared with the smallest hospitals (first quintile). A similar gradient was seen in a cohort of 100 hospitals with simulated equal poor performance (0%, 0%, 5%, 20%, and 85% in quintiles 1 to 5) effectively leaving 78% of poor performers undetected. Our results illustrate the disparity of impact that the current CMS method of hospital profiling has on hospitals with higher volumes, translating into lower thresholds for detection and reporting of poor performance.

Pixel sensors with slim edges and small pitches for the CMS upgrades for HL-LHC

DOE PAGES

Vernieri, Caterina; Bolla, Gino; Rivera, Ryan; ...

2016-06-07

Here, planar n-in-n silicon detectors with small pitches and slim edges are being investigated for the innermost layers of tracking devices for the foreseen upgrades of the LHC experiments. Sensor prototypes compatible with the CMS readout, fabricated by Sintef, were tested in the laboratory and with a 120 GeV/c proton beam at the Fermilab test beam facility before and after irradiation with up to 2 × 10 15 neq/cm 2 fluence. Preliminary results of the data analysis are presented.

Constraints on models of scalar and vector leptoquarks decaying to a quark and a neutrino at $$\\sqrt{s}=$$ 13 TeV

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

Sirunyan, Albert M; et al.

The results of a previous search by the CMS Collaboration for squarks and gluinos are reinterpreted to constrain models of leptoquark (LQ) production. The search considers jets in association with a transverse momentum imbalance, using themore » $$M_\\mathrm{T2}$$ variable. The analysis uses proton-proton collision data at $$\\sqrt{s}=$$ 13 TeV, recorded with the CMS detector at the LHC in 2016 and corresponding to an integrated luminosity of 35.9 fb$$^{-1}$$. Leptoquark pair production is considered with LQ decays to a neutrino and a top, bottom, or light quark. This reinterpretation considers higher mass values than the original CMS search to constrain both scalar and vector LQs. Limits on the cross section for LQ pair production are derived at the 95% confidence level depending on the LQ decay mode. A vector LQ decaying with a 50% branching fraction to t$$\

Fast emulation of track reconstruction in the CMS simulation

NASA Astrophysics Data System (ADS)

Komm, Matthias; CMS Collaboration

2017-10-01

Simulated samples of various physics processes are a key ingredient within analyses to unlock the physics behind LHC collision data. Samples with more and more statistics are required to keep up with the increasing amounts of recorded data. During sample generation, significant computing time is spent on the reconstruction of charged particle tracks from energy deposits which additionally scales with the pileup conditions. In CMS, the FastSimulation package is developed for providing a fast alternative to the standard simulation and reconstruction workflow. It employs various techniques to emulate track reconstruction effects in particle collision events. Several analysis groups in CMS are utilizing the package, in particular those requiring many samples to scan the parameter space of physics models (e.g. SUSY) or for the purpose of estimating systematic uncertainties. The strategies for and recent developments in this emulation are presented, including a novel, flexible implementation of tracking emulation while retaining a sufficient, tuneable accuracy.

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.

Measurement of the semileptonic t\\overline{t} + γ production cross section in pp collisions at √{s}=8 TeV

NASA Astrophysics Data System (ADS)

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hartl, C.; Hörmann, N.; Hrubec, J.; Jeitler, M.; König, A.; Krätschmer, I.; Liko, D.; Matsushita, T.; Mikulec, I.; Rabady, D.; Rad, N.; Rahbaran, B.; Rohringer, H.; Schieck, J.; Strauss, J.; Waltenberger, W.; Wulz, C.-E.; Dvornikov, O.; Makarenko, V.; Mossolov, V.; Gonzalez, J. Suarez; Zykunov, V.; Shumeiko, N.; Alderweireldt, S.; De Wolf, E. A.; Janssen, X.; Lauwers, J.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Zeid, S. Abu; Blekman, F.; D'Hondt, J.; Daci, N.; De Bruyn, I.; Deroover, K.; Lowette, S.; Moortgat, S.; Moreels, L.; Olbrechts, A.; Python, Q.; Skovpen, K.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Parijs, I.; Brun, H.; Clerbaux, B.; De Lentdecker, G.; Delannoy, H.; Fasanella, G.; Favart, L.; Goldouzian, R.; Grebenyuk, A.; Karapostoli, G.; Lenzi, T.; Léonard, A.; Luetic, J.; Maerschalk, T.; Marinov, A.; Randle-conde, A.; Seva, T.; Velde, C. Vander; Vanlaer, P.; Vannerom, D.; Yonamine, R.; Zenoni, F.; Zhang, F.; Cimmino, A.; Cornelis, T.; Dobur, D.; Fagot, A.; Gul, M.; Khvastunov, I.; Poyraz, D.; Salva, S.; Schöfbeck, R.; Tytgat, M.; Van Driessche, W.; Yazgan, E.; Zaganidis, N.; Bakhshiansohi, H.; Beluffi, C.; Bondu, O.; Brochet, S.; Bruno, G.; Caudron, A.; De Visscher, S.; Delaere, C.; Delcourt, M.; Francois, B.; Giammanco, A.; Jafari, A.; Komm, M.; Krintiras, G.; Lemaitre, V.; Magitteri, A.; Mertens, A.; Musich, M.; Piotrzkowski, K.; Quertenmont, L.; Selvaggi, M.; Marono, M. Vidal; Wertz, S.; Beliy, N.; Júnior, W. L. Aldá; Alves, F. L.; Alves, G. A.; Brito, L.; Hensel, C.; Moraes, A.; Pol, M. E.; Teles, P. Rebello; Chagas, E. Belchior Batista Das; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; Da Silveira, G. G.; De Jesus Damiao, D.; De Oliveira Martins, C.; De Souza, S. Fonseca; Guativa, L. M. Huertas; Malbouisson, H.; Figueiredo, D. Matos; Herrera, C. Mora; Mundim, L.; Nogima, H.; Da Silva, W. L. Prado; Santoro, A.; Sznajder, A.; Manganote, E. J. Tonelli; Da Silva De Araujo, F. Torres; Pereira, A. Vilela; Ahuja, S.; Bernardes, C. A.; Dogra, S.; Tomei, T. R. Fernandez Perez; Gregores, E. M.; Mercadante, P. G.; Moon, C. S.; Novaes, S. F.; Padula, Sandra S.; Abad, D. Romero; Vargas, J. C. Ruiz; Aleksandrov, A.; Hadjiiska, R.; Iaydjiev, P.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Vutova, M.; Dimitrov, A.; Glushkov, I.; Litov, L.; Pavlov, B.; Petkov, P.; Fang, W.; Ahmad, M.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Chen, Y.; Cheng, T.; Jiang, C. H.; Leggat, D.; Liu, Z.; Romeo, F.; Ruan, M.; Shaheen, S. M.; Spiezia, A.; Tao, J.; Wang, C.; Wang, Z.; Zhang, H.; Zhao, J.; Ban, Y.; Chen, G.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Avila, C.; Cabrera, A.; Sierra, L. F. Chaparro; Florez, C.; Gomez, J. P.; Hernández, C. F. González; Alvarez, J. D. Ruiz; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Puljak, I.; Cipriano, P. M. Ribeiro; Sculac, T.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Ferencek, D.; Kadija, K.; Mesic, B.; Susa, T.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Tsiakkouri, D.; Finger, M.; Finger, M.; Jarrin, E. Carrera; El-khateeb, E.; Elgammal, S.; Mohamed, A.; Kadastik, M.; Perrini, L.; Raidal, M.; Tiko, A.; Veelken, C.; Eerola, P.; Pekkanen, J.; Voutilainen, M.; Härkönen, J.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Tuominiemi, J.; Tuovinen, E.; Wendland, L.; Talvitie, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. L.; Favaro, C.; Ferri, F.; Ganjour, S.; Ghosh, S.; Givernaud, A.; Gras, P.; de Monchenault, G. Hamel; Jarry, P.; Kucher, I.; Locci, E.; Machet, M.; Malcles, J.; Rander, J.; Rosowsky, A.; Titov, M.; Abdulsalam, A.; Antropov, I.; Baffioni, S.; Beaudette, F.; Busson, P.; Cadamuro, L.; Chapon, E.; Charlot, C.; Davignon, O.; de Cassagnac, R. Granier; Jo, M.; Lisniak, S.; Miné, P.; Nguyen, M.; Ochando, C.; Ortona, G.; Paganini, P.; Pigard, P.; Regnard, S.; Salerno, R.; Sirois, Y.; Leiton, A. G. Stahl; Strebler, T.; Yilmaz, Y.; Zabi, A.; Zghiche, A.; Agram, J.-L.; Andrea, J.; Aubin, A.; Bloch, D.; Brom, J.-M.; Buttignol, M.; Chabert, E. C.; Chanon, N.; Collard, C.; Conte, E.; Coubez, X.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Le Bihan, A.-C.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Bernet, C.; Boudoul, G.; Montoya, C. A. Carrillo; Chierici, R.; Contardo, D.; Courbon, B.; Depasse, P.; El Mamouni, H.; Fay, J.; Gascon, S.; Gouzevitch, M.; Grenier, G.; Ille, B.; Lagarde, F.; Laktineh, I. B.; Lethuillier, M.; Mirabito, L.; Pequegnot, A. L.; Perries, S.; Popov, A.; Sabes, D.; Sordini, V.; Donckt, M. Vander; Verdier, P.; Viret, S.; Khvedelidze, A.; Lomidze, D.; Autermann, C.; Beranek, S.; Feld, L.; Kiesel, M. 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E.; Kara, O.; Kiminsu, U.; Oglakci, M.; Onengut, G.; Ozdemir, K.; Cerci, D. Sunar; Tali, B.; Topakli, H.; Turkcapar, S.; Zorbakir, I. S.; Zorbilmez, C.; Bilin, B.; Bilmis, S.; Isildak, B.; Karapinar, G.; Yalvac, M.; Zeyrek, M.; Gülmez, E.; Kaya, M.; Kaya, O.; Yetkin, E. A.; Yetkin, T.; Cakir, A.; Cankocak, K.; Sen, S.; Grynyov, B.; Levchuk, L.; Sorokin, P.; Aggleton, R.; Ball, F.; Beck, L.; Brooke, J. J.; Burns, D.; Clement, E.; Cussans, D.; Flacher, H.; Goldstein, J.; Grimes, M.; Heath, G. P.; Heath, H. F.; Jacob, J.; Kreczko, L.; Lucas, C.; Newbold, D. M.; Paramesvaran, S.; Poll, A.; Sakuma, T.; El Nasr-storey, S. Seif; Smith, D.; Smith, V. J.; Bell, K. W.; Belyaev, A.; Brew, C.; Brown, R. M.; Calligaris, L.; Cieri, D.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Olaiya, E.; Petyt, D.; Shepherd-Themistocleous, C. H.; Thea, A.; Tomalin, I. R.; Williams, T.; Baber, M.; Bainbridge, R.; Buchmuller, O.; Bundock, A.; Burton, D.; Casasso, S.; Citron, M.; Colling, D.; Corpe, L.; Dauncey, P.; Davies, G.; De Wit, A.; Negra, M. Della; Di Maria, R.; Dunne, P.; Elwood, A.; Futyan, D.; Haddad, Y.; Hall, G.; Iles, G.; James, T.; Lane, R.; Laner, C.; Lucas, R.; Lyons, L.; Magnan, A.-M.; Malik, S.; Mastrolorenzo, L.; Nash, J.; Nikitenko, A.; Pela, J.; Penning, B.; Pesaresi, M.; Raymond, D. M.; Richards, A.; Rose, A.; Scott, E.; Seez, C.; Summers, S.; Tapper, A.; Uchida, K.; Acosta, M. Vazquez; Virdee, T.; Wright, J.; Zenz, S. C.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Reid, I. D.; Symonds, P.; Teodorescu, L.; Turner, M.; Borzou, A.; Call, K.; Dittmann, J.; Hatakeyama, K.; Liu, H.; Pastika, N.; Bartek, R.; Dominguez, A.; Buccilli, A.; Cooper, S. I.; Henderson, C.; Rumerio, P.; West, C.; Arcaro, D.; Avetisyan, A.; Bose, T.; Gastler, D.; Rankin, D.; Richardson, C.; Rohlf, J.; Sulak, L.; Zou, D.; Benelli, G.; Cutts, D.; Garabedian, A.; Hakala, J.; Heintz, U.; Hogan, J. M.; Jesus, O.; Kwok, K. H. M.; Laird, E.; Landsberg, G.; Mao, Z.; Narain, M.; Piperov, S.; Sagir, S.; Spencer, E.; Syarif, R.; Breedon, R.; Burns, D.; De La Barca Sanchez, M. Calderon; Chauhan, S.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Erbacher, R.; Flores, C.; Funk, G.; Gardner, M.; Ko, W.; Lander, R.; Mclean, C.; Mulhearn, M.; Pellett, D.; Pilot, J.; Shalhout, S.; Shi, M.; Smith, J.; Squires, M.; Stolp, D.; Tos, K.; Tripathi, M.; Bachtis, M.; Bravo, C.; Cousins, R.; Dasgupta, A.; Florent, A.; Hauser, J.; Ignatenko, M.; Mccoll, N.; Saltzberg, D.; Schnaible, C.; Valuev, V.; Weber, M.; Bouvier, E.; Burt, K.; Clare, R.; Ellison, J.; Gary, J. W.; Shirazi, S. M. A. Ghiasi; Hanson, G.; Heilman, J.; Jandir, P.; Kennedy, E.; Lacroix, F.; Long, O. R.; Negrete, M. Olmedo; Paneva, M. I.; Shrinivas, A.; Si, W.; Wei, H.; Wimpenny, S.; Yates, B. R.; Branson, J. G.; Cerati, G. B.; Cittolin, S.; Derdzinski, M.; Gerosa, R.; Holzner, A.; Klein, D.; Krutelyov, V.; Letts, J.; Macneill, I.; Olivito, D.; Padhi, S.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Tadel, M.; Vartak, A.; Wasserbaech, S.; Welke, C.; Wood, J.; Würthwein, F.; Yagil, A.; Porta, G. Zevi Della; Amin, N.; Bhandari, R.; Bradmiller-Feld, J.; Campagnari, C.; Dishaw, A.; Dutta, V.; Sevilla, M. Franco; George, C.; Golf, F.; Gouskos, L.; Gran, J.; Heller, R.; Incandela, J.; Mullin, S. D.; Ovcharova, A.; Qu, H.; Richman, J.; Stuart, D.; Suarez, I.; Yoo, J.; Anderson, D.; Bendavid, J.; Bornheim, A.; Bunn, J.; Duarte, J.; Lawhorn, J. M.; Mott, A.; Newman, H. B.; Pena, C.; Spiropulu, M.; Vlimant, J. R.; Xie, S.; Zhu, R. Y.; Andrews, M. B.; Ferguson, T.; Paulini, M.; Russ, J.; Sun, M.; Vogel, H.; Vorobiev, I.; Weinberg, M.; Cumalat, J. P.; Ford, W. T.; Jensen, F.; Johnson, A.; Krohn, M.; Leontsinis, S.; Mulholland, T.; Stenson, K.; Wagner, S. R.; Alexander, J.; Chaves, J.; Chu, J.; Dittmer, S.; Mcdermott, K.; Mirman, N.; Kaufman, G. Nicolas; Patterson, J. R.; Rinkevicius, A.; Ryd, A.; Skinnari, L.; Soffi, L.; Tan, S. M.; Tao, Z.; Thom, J.; Tucker, J.; Wittich, P.; Zientek, M.; Winn, D.; Abdullin, S.; Albrow, M.; Apollinari, G.; Apresyan, A.; Banerjee, S.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bolla, G.; Burkett, K.; Butler, J. N.; Cheung, H. W. K.; Chlebana, F.; Cihangir, S.; Cremonesi, M.; Elvira, V. D.; Fisk, I.; Freeman, J.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Hare, D.; Harris, R. M.; Hasegawa, S.; Hirschauer, J.; Hu, Z.; Jayatilaka, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kreis, B.; Lammel, S.; Linacre, J.; Lincoln, D.; Lipton, R.; Liu, M.; Liu, T.; De Sá, R. Lopes; Lykken, J.; Maeshima, K.; Magini, N.; Marraffino, J. M.; Maruyama, S.; Mason, D.; McBride, P.; Merkel, P.; Mrenna, S.; Nahn, S.; O'Dell, V.; Pedro, K.; Prokofyev, O.; Rakness, G.; Ristori, L.; Sexton-Kennedy, E.; Soha, A.; Spalding, W. J.; Spiegel, L.; Stoynev, S.; Strait, J.; Strobbe, N.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vernieri, C.; Verzocchi, M.; Vidal, R.; Wang, M.; Weber, H. A.; Whitbeck, A.; Wu, Y.; Acosta, D.; Avery, P.; Bortignon, P.; Bourilkov, D.; Brinkerhoff, A.; Carnes, A.; Carver, M.; Curry, D.; Das, S.; Field, R. D.; Furic, I. K.; Konigsberg, J.; Korytov, A.; Low, J. F.; Ma, P.; Matchev, K.; Mei, H.; Mitselmakher, G.; Rank, D.; Shchutska, L.; Sperka, D.; Thomas, L.; Wang, J.; Wang, S.; Yelton, J.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Ackert, A.; Adams, T.; Askew, A.; Bein, S.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Kolberg, T.; Prosper, H.; Santra, A.; Yohay, R.; Baarmand, M. M.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Bucinskaite, I.; Cavanaugh, R.; Evdokimov, O.; Gauthier, L.; Gerber, C. E.; Hofman, D. J.; Jung, K.; Gonzalez, I. D. Sandoval; Varelas, N.; Wang, H.; Wu, Z.; Zakaria, M.; Zhang, J.; Bilki, B.; Clarida, W.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Snyder, C.; Tiras, E.; Wetzel, J.; Yi, K.; Blumenfeld, B.; Cocoros, A.; Eminizer, N.; Fehling, D.; Feng, L.; Gritsan, A. V.; Maksimovic, P.; Roskes, J.; Sarica, U.; Swartz, M.; Xiao, M.; You, C.; Al-bataineh, A.; Baringer, P.; Bean, A.; Boren, S.; Bowen, J.; Castle, J.; Forthomme, L.; Kenny, R. P.; Khalil, S.; Kropivnitskaya, A.; Majumder, D.; Mcbrayer, W.; Murray, M.; Sanders, S.; Stringer, R.; Takaki, J. D. Tapia; Wang, Q.; Ivanov, A.; Kaadze, K.; Maravin, Y.; Mohammadi, A.; Saini, L. K.; Skhirtladze, N.; Toda, S.; Rebassoo, F.; Wright, D.; Anelli, C.; Baden, A.; Baron, O.; Belloni, A.; Calvert, B.; Eno, S. C.; Ferraioli, C.; Gomez, J. A.; Hadley, N. J.; Jabeen, S.; Jeng, G. Y.; Kellogg, R. G.; Kunkle, J.; Mignerey, A. C.; Ricci-Tam, F.; Shin, Y. H.; Skuja, A.; Tonjes, M. B.; Tonwar, S. C.; Abercrombie, D.; Allen, B.; Apyan, A.; Azzolini, V.; Barbieri, R.; Baty, A.; Bi, R.; Bierwagen, K.; Brandt, S.; Busza, W.; Cali, I. A.; D'Alfonso, M.; Demiragli, Z.; Ceballos, G. Gomez; Goncharov, M.; Hsu, D.; Iiyama, Y.; Innocenti, G. M.; Klute, M.; Kovalskyi, D.; Krajczar, K.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Maier, B.; Marini, A. C.; Mcginn, C.; Mironov, C.; Narayanan, S.; Niu, X.; Paus, C.; Roland, C.; Roland, G.; Salfeld-Nebgen, J.; Stephans, G. S. F.; Tatar, K.; Velicanu, D.; Wang, J.; Wang, T. W.; Wyslouch, B.; Benvenuti, A. C.; Chatterjee, R. M.; Evans, A.; Hansen, P.; Kalafut, S.; Kao, S. C.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Tambe, N.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bloom, K.; Claes, D. R.; Fangmeier, C.; Suarez, R. Gonzalez; Kamalieddin, R.; Kravchenko, I.; Rodrigues, A. Malta; Monroy, J.; Siado, J. E.; Snow, G. R.; Stieger, B.; Alyari, M.; Dolen, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Kaisen, J.; Nguyen, D.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; De Lima, R. Teixeira; Trocino, D.; Wang, R.-J.; Wood, D.; Bhattacharya, S.; Charaf, O.; Hahn, K. A.; Kumar, A.; Mucia, N.; Odell, N.; Pollack, B.; Schmitt, M. H.; Sung, K.; Trovato, M.; Velasco, M.; Dev, N.; Hildreth, M.; Anampa, K. Hurtado; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Rupprecht, N.; Smith, G.; Taroni, S.; Wayne, M.; Wolf, M.; Woodard, A.; Alimena, J.; Antonelli, L.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Francis, B.; Hart, A.; Hill, C.; Hughes, R.; Ji, W.; Liu, B.; Luo, W.; Puigh, D.; Winer, B. L.; Wulsin, H. W.; Cooperstein, S.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Lange, D.; Luo, J.; Marlow, D.; Medvedeva, T.; Mei, K.; Ojalvo, I.; Olsen, J.; Palmer, C.; Piroué, P.; Stickland, D.; Svyatkovskiy, A.; Tully, C.; Malik, S.; Barker, A.; Barnes, V. E.; Folgueras, S.; Gutay, L.; Jha, M. K.; Jones, M.; Jung, A. W.; Khatiwada, A.; Miller, D. H.; Neumeister, N.; Schulte, J. F.; Shi, X.; Sun, J.; Wang, F.; Xie, W.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Chen, Z.; Ecklund, K. M.; Geurts, F. J. M.; Guilbaud, M.; Li, W.; Michlin, B.; Northup, M.; Padley, B. P.; Roberts, J.; Rorie, J.; Tu, Z.; Zabel, J.; Betchart, B.; Bodek, A.; de Barbaro, P.; Demina, R.; Duh, Y. t.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Han, J.; Hindrichs, O.; Khukhunaishvili, A.; Lo, K. H.; Tan, P.; Verzetti, M.; Agapitos, A.; Chou, J. P.; Gershtein, Y.; Espinosa, T. A. Gómez; Halkiadakis, E.; Heindl, M.; Hughes, E.; Kaplan, S.; Elayavalli, R. Kunnawalkam; Kyriacou, S.; Lath, A.; Nash, K.; Osherson, M.; Saka, H.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Delannoy, A. G.; Foerster, M.; Heideman, J.; Riley, G.; Rose, K.; Spanier, S.; Thapa, K.; Bouhali, O.; Celik, A.; Dalchenko, M.; De Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Juska, E.; Kamon, T.; Mueller, R.; Pakhotin, Y.; Patel, R.; Perloff, A.; Perniè, L.; Rathjens, D.; Safonov, A.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Damgov, J.; De Guio, F.; Dragoiu, C.; Dudero, P. R.; Faulkner, J.; Gurpinar, E.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Peltola, T.; Undleeb, S.; Volobouev, I.; Wang, Z.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Melo, A.; Ni, H.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Barria, P.; Cox, B.; Goodell, J.; Hirosky, R.; Ledovskoy, A.; Li, H.; Neu, C.; Sinthuprasith, T.; Sun, X.; Wang, Y.; Wolfe, E.; Xia, F.; Clarke, C.; Harr, R.; Karchin, P. E.; Sturdy, J.; Belknap, D. A.; Buchanan, J.; Caillol, C.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Perry, T.; Pierro, G. A.; Polese, G.; Ruggles, T.; Savin, A.; Smith, N.; Smith, W. H.; Taylor, D.; Woods, N.

2017-10-01

A measurement of the cross section for top quark-antiquark ( t\\overline{t} ) pairs produced in association with a photon in proton-proton collisions at √{s}=8 TeV is presented. The analysis uses data collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 19.7 fb1. The signal is defined as the production of a t\\overline{t} pair in association with a photon having a transverse energy larger than 25 GeV and an absolute pseudorapidity smaller than 1.44. The measurement is performed in the fiducial phase space corresponding to the semileptonic decay chain of the t\\overline{t} pair, and the cross section is measured relative to the inclusive t\\overline{t} pair production cross section. The fiducial cross section for associated t\\overline{t} pair and photon production is found to be 127 ±27 (stat+syst) fb per semileptonic final state. The measured value is in agreement with the theoretical prediction. [Figure not available: see fulltext.

Measurement of the semileptonic $$ \\mathrm{t}\\overline{\\mathrm{t}} $$ + γ production cross section in pp collisions at $$ \\sqrt{s}=8 $$ TeV

DOE PAGES

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; ...

2017-10-01

A measurement of the cross section for top quark-antiquark (tt¯) pairs produced in association with a photon in proton-proton collisions at √s = 8 TeV is presented. The analysis uses data collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 19.7 fb 1. The signal is defined as the production of a tt¯ pair in association with a photon having a transverse energy larger than 25 GeV and an absolute pseudorapidity smaller than 1.44. The measurement is performed in the fiducial phase space corresponding to the semileptonic decay chain of the tt¯ pair, and themore » cross section is measured relative to the inclusive tt¯ pair production cross section. The fiducial cross section for associated tt¯ pair and photon production is found to be 127 ±27 (stat+syst) fb per semileptonic final state. In conclusion, the measured value is in agreement with the theoretical prediction.« less

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...

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

PubMed

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

2012-02-21

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

Interaction of Bacterial Phenazines with Colistimethate in Bronchial Epithelial Cells.

PubMed

Mossine, Valeri V; Chance, Deborah L; Waters, James K; Mawhinney, Thomas P

2018-05-21

Multidrug-resistant bacterial infections are being increasingly treated in clinics with polymyxins, a class of antibiotics associated with adverse effects in the kidney, nervous system, or airways of a significant proportion of human and animal patients. Although many of the resistant pathogens display enhanced virulence, a hazard of cytotoxic interactions between polymyxin antibiotics and bacterial virulence factors (VFs) has not been assessed, to date. We report here on testing paired combinations of four Pseudomonas aeruginosa VF phenazine toxins, pyocyanin (PYO), 1-hydroxyphenazine (1-HP), phenazine-1-carboxylic acid (PCA), phenazine-1-carboxamide (PCN), and two commonly prescribed polymyxin drugs, colistimethate (CMS)/colistin and polymyxin B, in three human airway cell lines, BEAS-2B, HBE-1, and CFT-1. Cytotoxicities of individual antibiotics, toxins, and their combinations were evaluated by simultaneous measurement of mitochondrial metabolic, total transcriptional/translational, and the Nrf2 stress response regulator activities in treated cells. Two phenazines, PYO and 1-HP, were cytotoxic at clinically relevant concentrations (100-150 μM) and prompted a significant increase in the oxidative stress-induced transcriptional activity in surviving cells. The polymyxin antibiotics arrested the cell proliferation at clinically achievable (< 1 mM) concentrations, as well, with CMS displaying a surprisingly high cytotoxicity (ED 50 = 180 μM) in BEAS-2B. The dose-response curves were probed by the median-effect analysis which established a synergistically enhanced cytotoxicity of the PYO/CMS combination in all three airway cell lines; a particularly strong effect was observed in the BEAS-2B cells, with the combination index (CI) = 0.27 at ED 50 PCA, PCN, and 1-HP potentiated CMS cytotoxicity to a smaller extent. The cytotoxicity of CMS could be reduced with 10 mM N -acetyl-cysteine. Iron chelators, while ineffective against the polymyxins, could rescue all three bronchial epithelial cell lines treated with lethal PYO or CMS/PYO doses. These findings suggest further evaluations of CMS safety are needed, along with a search for means to moderate the potentially cytotoxic interactions. Copyright © 2018 Mossine et al.

The miRNAs and their regulatory networks responsible for pollen abortion in Ogura-CMS Chinese cabbage revealed by high-throughput sequencing of miRNAs, degradomes, and transcriptomes

PubMed Central

Wei, Xiaochun; Zhang, Xiaohui; Yao, Qiuju; Yuan, Yuxiang; Li, Xixiang; Wei, Fang; Zhao, Yanyan; Zhang, Qiang; Wang, Zhiyong; Jiang, Wusheng; Zhang, Xiaowei

2015-01-01

Chinese cabbage (Brassica rapa ssp. pekinensis) is one of the most important vegetables in Asia and is cultivated across the world. Ogura-type cytoplasmic male sterility (Ogura-CMS) has been widely used in the hybrid breeding industry for Chinese cabbage and many other cruciferous vegetables. Although, the cause of Ogura-CMS has been localized to the orf138 locus in the mitochondrial genome, however, the mechanism by which nuclear genes respond to the mutation of the mitochondrial orf138 locus is unclear. In this study, a series of whole genome small RNA, degradome and transcriptome analyses were performed on both Ogura-CMS and its maintainer Chinese cabbage buds using deep sequencing technology. A total of 289 known miRNAs derived from 69 families (including 23 new families first reported in B. rapa) and 426 novel miRNAs were identified. Among these novel miRNAs, both 3-p and 5-p miRNAs were detected on the hairpin arms of 138 precursors. Ten known and 49 novel miRNAs were down-regulated, while one known and 27 novel miRNAs were up-regulated in Ogura-CMS buds compared to the fertile plants. Using degradome analysis, a total of 376 mRNAs were identified as targets of 30 known miRNA families and 100 novel miRNAs. A large fraction of the targets were annotated as reproductive development related. Our transcriptome profiling revealed that the expression of the targets was finely tuned by the miRNAs. Two novel miRNAs were identified that were specifically highly expressed in Ogura-CMS buds and sufficiently suppressed two pollen development essential genes: sucrose transporter SUC1 and H+-ATPase 6. These findings provide clues for the contribution of a potential miRNA regulatory network to bud development and pollen engenderation. This study contributes new insights to the communication between the mitochondria and chromosome and takes one step toward filling the gap in the regulatory network from the orf138 locus to pollen abortion in Ogura-CMS plants from a miRNA perspective. PMID:26557132

Risk factors for acute kidney injury in critically ill patients receiving high intravenous doses of colistin methanesulfonate and/or other nephrotoxic antibiotics: a retrospective cohort study

PubMed Central

2013-01-01

Introduction Use of colistin methanesulfonate (CMS) was abandoned in the 1970s because of excessive nephrotoxicity, but it has been reintroduced as a last-resort treatment for extensively drug-resistant infections caused by gram-negative bacteria (Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumonia). We conducted a retrospective cohort study to evaluate risk factors for new-onset acute kidney injury (AKI) in critically ill patients receiving high intravenous doses of colistin methanesulfonate and/or other nephrotoxic antibiotics. Methods The cohort consisted of 279 adults admitted to two general ICUs in teaching hospitals between 1 April 2009 and 30 June 2011 with 1) no evidence on admission of acute or chronic kidney disease; and 2) treatment for more than seven days with CMS and/or other nephrotoxic antimicrobials (NAs, that is, aminoglycosides, glycopeptides). Logistic regression analysis was used to identify risk factors associated with this outcome. Results The 279 cases that met the inclusion criteria included 147 patients treated with CMS, alone (n = 90) or with NAs (n = 57), and 132 treated with NAs alone. The 111 (40%) who developed AKI were significantly older and had significantly higher Simplified Acute Physiology Score II (SAPS II) scores than those who did not develop AKI, but rates of hypertension, diabetes mellitus and congestive heart failure were similar in the two groups. The final logistic regression model showed that in the 147 patients who received CMS alone or with NAs, onset of AKI during the ICU stay was associated with septic shock and with SAPS II scores ≥43. Similar results were obtained in the 222 patients treated with CMS alone or NAs alone. Conclusions In severely ill ICU patients without pre-existing renal disease who receive CMS high-dose for more than seven days, CMS therapy does not appear to be a risk factor for this outcome. Instead, the development of AKI was strongly correlated with the presence of septic shock and with the severity of the patients as reflected by the SAPS II score. PMID:23945197

The miRNAs and their regulatory networks responsible for pollen abortion in Ogura-CMS Chinese cabbage revealed by high-throughput sequencing of miRNAs, degradomes, and transcriptomes.

PubMed

Wei, Xiaochun; Zhang, Xiaohui; Yao, Qiuju; Yuan, Yuxiang; Li, Xixiang; Wei, Fang; Zhao, Yanyan; Zhang, Qiang; Wang, Zhiyong; Jiang, Wusheng; Zhang, Xiaowei

2015-01-01

Chinese cabbage (Brassica rapa ssp. pekinensis) is one of the most important vegetables in Asia and is cultivated across the world. Ogura-type cytoplasmic male sterility (Ogura-CMS) has been widely used in the hybrid breeding industry for Chinese cabbage and many other cruciferous vegetables. Although, the cause of Ogura-CMS has been localized to the orf138 locus in the mitochondrial genome, however, the mechanism by which nuclear genes respond to the mutation of the mitochondrial orf138 locus is unclear. In this study, a series of whole genome small RNA, degradome and transcriptome analyses were performed on both Ogura-CMS and its maintainer Chinese cabbage buds using deep sequencing technology. A total of 289 known miRNAs derived from 69 families (including 23 new families first reported in B. rapa) and 426 novel miRNAs were identified. Among these novel miRNAs, both 3-p and 5-p miRNAs were detected on the hairpin arms of 138 precursors. Ten known and 49 novel miRNAs were down-regulated, while one known and 27 novel miRNAs were up-regulated in Ogura-CMS buds compared to the fertile plants. Using degradome analysis, a total of 376 mRNAs were identified as targets of 30 known miRNA families and 100 novel miRNAs. A large fraction of the targets were annotated as reproductive development related. Our transcriptome profiling revealed that the expression of the targets was finely tuned by the miRNAs. Two novel miRNAs were identified that were specifically highly expressed in Ogura-CMS buds and sufficiently suppressed two pollen development essential genes: sucrose transporter SUC1 and H (+) -ATPase 6. These findings provide clues for the contribution of a potential miRNA regulatory network to bud development and pollen engenderation. This study contributes new insights to the communication between the mitochondria and chromosome and takes one step toward filling the gap in the regulatory network from the orf138 locus to pollen abortion in Ogura-CMS plants from a miRNA perspective.

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.

Developmental changes in electrophysiological characteristics of human induced Pluripotent Stem Cell-derived cardiomyocytes

PubMed Central

Ben-Ari, Meital; Naor, Shulamit; Zeevi-Levin, Naama; Schick, Revital; Ben Jehuda, Ronen; Reiter, Irina; Raveh, Amit; Grijnevitch, Inna; Barak, Omri; Rosen, Michael R.; Weissman, Amir; Binah, Ofer

2016-01-01

Background Previous studies proposed that throughout differentiation of human induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs) only 3 types of action potentials (AP) exist: nodal, atrial and ventricular-like. Objective To investigate whether there are precisely 3 phenotypes or a continuum exists among them, we tested 2 hypotheses: (1) during culture development a cardiac precursor cell is present that - depending on age - can evolve into the 3 phenotypes. (2) The predominant pattern is early prevalence of nodal phenotype, transient appearance of atrial phenotype, evolution to ventricular phenotype, and persistence of transitional phenotypes. Methods To test these hypotheses we: (1) performed FACS analysis of nodal, atrial and ventricular markers; (2) recorded AP from 280 7-to-95 day old iPSC-CMs; (3) analyzed AP characteristics. Results The major findings were: (1) FACS analysis of 30 and 60-day old cultures showed that an iPSC-CMs population shifts from nodal into atrial/ventricular phenotype, while including significant transitional populations.(2) The AP population did not consist of 3 distinct phenotypes; (3) Culture aging was associated with a shift from nodal to ventricular dominance, with a transient (57–70 days) appearance of atrial phenotype; (4) Beat Rate Variability was more prominent in nodal than ventricular cardiomyocytes while If density increased in older cultures. Conclusions From the onset of development the iPSC-CMs population includes nodal, atrial and ventricular AP and a broad spectrum of transitional phenotypes. The most readily distinguishable phenotype is atrial which appears only transiently, yet dominates at 57–70 days of evolution. PMID:27639456

42 CFR 431.992 - Corrective action plan.

Code of Federal Regulations, 2010 CFR

2010-10-01

... CMS, designed to reduce improper payments in each program based on its analysis of the error causes in... State must take the following actions: (1) Data analysis. States must conduct data analysis such as reviewing clusters of errors, general error causes, characteristics, and frequency of errors that are...

42 CFR 431.992 - Corrective action plan.

Code of Federal Regulations, 2011 CFR

2011-10-01

... CMS, designed to reduce improper payments in each program based on its analysis of the error causes in... State must take the following actions: (1) Data analysis. States must conduct data analysis such as reviewing clusters of errors, general error causes, characteristics, and frequency of errors that are...

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

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.

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.

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.

Human Embryonic Stem Cell-Derived Cardiomyocytes Self-Arrange with Areas of Different Subtypes During Differentiation.

PubMed

Vestergaard, Maj Linea; Grubb, Søren; Koefoed, Karen; Anderson-Jenkins, Zoe; Grunnet-Lauridsen, Kristina; Calloe, Kirstine; Clausen, Christian; Christensen, Søren Tvorup; Møllgård, Kjeld; Andersen, Claus Yding

2017-11-01

The derivation of functional cardiomyocytes (CMs) from human embryonic stem cells (hESCs) represents a unique way of studying human cardiogenesis, including the development of CM subtypes. In this study, we investigated the development and organization of hESC-derived cardiomyocytes (hESC-CMs) and examined how the expression levels of CM subtypes correspond to human in vivo cardiogenesis. Beating clusters were used to determine cardiac differentiation, which was evaluated by the expression of cardiac genes GATA4 and TNNT2 and subcellular localization of GATA4 and NKX2.5. Sharp electrode recordings to determine action potentials (APs) further revealed spatial organization of intracluster CM subtypes (ie, complex clusters). Nodal-, atrial-, and ventricular-like AP morphologies were detected within distinct regions of complex clusters. The ability of different CM subtypes to self-organize was documented by immunohistochemical analyses and a differential spatial expression of β-III tubulin, myosin light chain 2v (MLC-2V), and α-smooth muscle actin (α-SMA). Furthermore, all hESC-CM subtypes formed expressed primary cilia, which are known to coordinate cellular signaling pathways during cardiomyogenesis and heart development. This study expands the foundation for studying regulatory pathways for spatial and temporal CM differentiation during human cardiogenesis.

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...

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.

Probing New Physics with Jets at the LHC

ScienceCinema

Harris, Robert

2017-12-09

The Large Hadron Collider at CERN has the potential to make a major discovery as early as 2008 from simple measurements of events with two high energy jets. This talk will present the jet trigger and analysis plans of the CMS collaboration, which were produced at the LHC Physics Center at Fermilab. Plans to search the two jet channel for generic signals of new particles and forces will be discussed. I will present the anticipated sensitivity of the CMS experiment to a variety of models of new physics, including quark compositeness, technicolor, superstrings, extra dimensions and grand unification.

Medicare Beneficiary Satisfaction with Durable Medical Equipment Suppliers

PubMed Central

Hoerger, Thomas J.; Finkelstein, Eric A.; Bernard, Shulamit L.

2001-01-01

CMS has recently launched a series of initiatives to control Medicare spending on durable medical equipment (DME) and prosthetics, orthotics, and supplies (DMEPOS). An important question is how these initiatives will affect beneficiary satisfaction. Using survey data, we analyze Medicare beneficiary satisfaction with DMEPOS suppliers in two Florida counties. Our results show that beneficiaries are currently highly satisfied with their DMEPOS suppliers. Beneficiary satisfaction is positively related to rapid delivery, training, dependability, and frequency of service. Results of our analysis can be used as baseline estimates in evaluating CMS initiatives to reduce Medicare payments for DMEPOS. PMID:12500367

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.

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

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.

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

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

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.

Measurements of the Higgs boson production and decay rates and constraints on its couplings from a combined ATLAS and CMS analysis of the LHC pp collision data at $$\\sqrt{s}=7 $$ and 8 TeV

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

Aad, G.; Abbott, B.; Abdallah, J.

Combined ATLAS and CMS measurements of the Higgs boson production and decay rates, as well as constraints on its couplings to vector bosons and fermions, are presented. The combination is based on the analysis of five production processes, namely gluon fusion, vector boson fusion, and associated production with a W or a Z boson or a pair of top quarks, and of the six decay modes H → ZZ, W W , γγ, ττ, bb, and μμ. All results are reported assuming a value of 125.09 GeV for the Higgs boson mass, the result of the combined measurement by the ATLAS and CMS experiments. The analysis uses the CERN LHC proton-proton collision data recorded by the ATLAS and CMS experiments in 2011 and 2012, corresponding to integrated luminosities per experiment of approximately 5 fbmore » $$^{–1}$$ at $$ \\sqrt{s}=7 $$ TeV and 20 fb$$^{–1}$$ at $$ \\sqrt{s}=8 $$ TeV. The Higgs boson production and decay rates measured by the two experiments are combined within the context of three generic parameterisations: two based on cross sections and branching fractions, and one on ratios of coupling modifiers. Several interpretations of the measurements with more model-dependent parameterisations are also given. The combined signal yield relative to the Standard Model prediction is measured to be 1.09 ± 0.11. The combined measurements lead to observed significances for the vector boson fusion production process and for the H → ττ decay of 5.4 and 5.5 standard deviations, respectively. In conclusion, the data are consistent with the Standard Model predictions for all parameterisations considered.« less

Measurements of the Higgs boson production and decay rates and constraints on its couplings from a combined ATLAS and CMS analysis of the LHC pp collision data at $$\\sqrt{s}=7 $$ and 8 TeV

DOE PAGES

Aad, G.; Abbott, B.; Abdallah, J.; ...

2016-08-05

Combined ATLAS and CMS measurements of the Higgs boson production and decay rates, as well as constraints on its couplings to vector bosons and fermions, are presented. The combination is based on the analysis of five production processes, namely gluon fusion, vector boson fusion, and associated production with a W or a Z boson or a pair of top quarks, and of the six decay modes H → ZZ, W W , γγ, ττ, bb, and μμ. All results are reported assuming a value of 125.09 GeV for the Higgs boson mass, the result of the combined measurement by the ATLAS and CMS experiments. The analysis uses the CERN LHC proton-proton collision data recorded by the ATLAS and CMS experiments in 2011 and 2012, corresponding to integrated luminosities per experiment of approximately 5 fbmore » $$^{–1}$$ at $$ \\sqrt{s}=7 $$ TeV and 20 fb$$^{–1}$$ at $$ \\sqrt{s}=8 $$ TeV. The Higgs boson production and decay rates measured by the two experiments are combined within the context of three generic parameterisations: two based on cross sections and branching fractions, and one on ratios of coupling modifiers. Several interpretations of the measurements with more model-dependent parameterisations are also given. The combined signal yield relative to the Standard Model prediction is measured to be 1.09 ± 0.11. The combined measurements lead to observed significances for the vector boson fusion production process and for the H → ττ decay of 5.4 and 5.5 standard deviations, respectively. In conclusion, the data are consistent with the Standard Model predictions for all parameterisations considered.« less

Measurements of the Higgs boson production and decay rates and constraints on its couplings from a combined ATLAS and CMS analysis of the LHC pp collision data at √{s}=7 and 8 TeV

NASA Astrophysics Data System (ADS)

Aad, G.; Abbott, B.; Abdallah, J.; Abdinov, O.; Abeloos, B.; Aben, R.; AbouZeid, O. S.; Abraham, N. L.; Abramowicz, H.; Abreu, H.; Abreu, R.; Abulaiti, Y.; Acharya, B. S.; Adamczyk, L.; Adams, D. L.; Adelman, J.; Adomeit, S.; Adye, T.; Affolder, A. A.; Agatonovic-Jovin, T.; Agricola, J.; Aguilar-Saavedra, J. A.; Ahlen, S. P.; Ahmadov, F.; Aielli, G.; Akerstedt, H.; Åkesson, T. P. A.; Akimov, A. V.; Alberghi, G. L.; Albert, J.; Albrand, S.; Alconada Verzini, M. J.; Aleksa, M.; Aleksandrov, I. N.; Alexa, C.; Alexander, G.; Alexopoulos, T.; Alhroob, M.; Aliev, M.; Alimonti, G.; Alison, J.; Alkire, S. P.; Allbrooke, B. M. M.; Allen, B. W.; Allport, P. P.; Aloisio, A.; Alonso, A.; Alonso, F.; Alpigiani, C.; Alstaty, M.; Alvarez Gonzalez, B.; Álvarez Piqueras, D.; Alviggi, M. G.; Amadio, B. T.; Amako, K.; Amaral Coutinho, Y.; Amelung, C.; Amidei, D.; Amor Dos Santos, S. P.; Amorim, A.; Amoroso, S.; Amundsen, G.; Anastopoulos, C.; Ancu, L. S.; Andari, N.; Andeen, T.; Anders, C. F.; Anders, G.; Anders, J. K.; Anderson, K. J.; Andreazza, A.; Andrei, V.; Angelidakis, S.; Angelozzi, I.; Anger, P.; Angerami, A.; Anghinolfi, F.; Anisenkov, A. V.; Anjos, N.; Annovi, A.; Antonelli, M.; Antonov, A.; Antos, J.; Anulli, F.; Aoki, M.; Aperio Bella, L.; Arabidze, G.; Arai, Y.; Araque, J. P.; Arce, A. T. H.; Arduh, F. A.; Arguin, J.-F.; Argyropoulos, S.; Arik, M.; Armbruster, A. J.; Armitage, L. J.; Arnaez, O.; Arnold, H.; Arratia, M.; Arslan, O.; Artamonov, A.; Artoni, G.; Artz, S.; Asai, S.; Asbah, N.; Ashkenazi, A.; Åsman, B.; Asquith, L.; Assamagan, K.; Astalos, R.; Atkinson, M.; Atlay, N. B.; Augsten, K.; Avolio, G.; Axen, B.; Ayoub, M. K.; Azuelos, G.; Baak, M. A.; Baas, A. E.; Baca, M. J.; Bachacou, H.; Bachas, K.; Backes, M.; Backhaus, M.; Bagiacchi, P.; Bagnaia, P.; Bai, Y.; Baines, J. T.; Baker, O. K.; Baldin, E. M.; Balek, P.; Balestri, T.; Balli, F.; Balunas, W. K.; Banas, E.; Banerjee, Sw.; Bannoura, A. A. E.; Barak, L.; Barberio, E. L.; Barberis, D.; Barbero, M.; Barillari, T.; Barklow, T.; Barlow, N.; Barnes, S. L.; Barnett, B. M.; Barnett, R. M.; Barnovska, Z.; Baroncelli, A.; Barone, G.; Barr, A. J.; Barranco Navarro, L.; Barreiro, F.; Barreiro Guimarães da Costa, J.; Bartoldus, R.; Barton, A. E.; Bartos, P.; Basalaev, A.; Bassalat, A.; Bates, R. L.; Batista, S. J.; Batley, J. R.; Battaglia, M.; Bauce, M.; Bauer, F.; Bawa, H. S.; Beacham, J. B.; Beattie, M. D.; Beau, T.; Beauchemin, P. H.; Bechtle, P.; Beck, H. P.; Becker, K.; Becker, M.; Beckingham, M.; Becot, C.; Beddall, A. J.; Beddall, A.; Bednyakov, V. A.; Bedognetti, M.; Bee, C. P.; Beemster, L. J.; Beermann, T. A.; Begel, M.; Behr, J. K.; Belanger-Champagne, C.; Bell, A. S.; Bella, G.; Bellagamba, L.; Bellerive, A.; Bellomo, M.; Belotskiy, K.; Beltramello, O.; Belyaev, N. L.; Benary, O.; Benchekroun, D.; Bender, M.; Bendtz, K.; Benekos, N.; Benhammou, Y.; Benhar Noccioli, E.; Benitez, J.; Benjamin, D. P.; Bensinger, J. 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B.; Christodoulou, V.; Chromek-Burckhart, D.; Chudoba, J.; Chuinard, A. J.; Chwastowski, J. J.; Chytka, L.; Ciapetti, G.; Ciftci, A. K.; Cinca, D.; Cindro, V.; Cioara, I. A.; Ciocio, A.; Cirotto, F.; Citron, Z. H.; Citterio, M.; Ciubancan, M.; Clark, A.; Clark, B. L.; Clark, M. R.; Clark, P. J.; Clarke, R. N.; Clement, C.; Coadou, Y.; Cobal, M.; Coccaro, A.; Cochran, J.; Coffey, L.; Colasurdo, L.; Cole, B.; Colijn, A. P.; Collot, J.; Colombo, T.; Compostella, G.; Conde Muiño, P.; Coniavitis, E.; Connell, S. H.; Connelly, I. A.; Consorti, V.; Constantinescu, S.; Conti, G.; Conventi, F.; Cooke, M.; Cooper, B. D.; Cooper-Sarkar, A. M.; Cormier, K. J. R.; Cornelissen, T.; Corradi, M.; Corriveau, F.; Corso-Radu, A.; Cortes-Gonzalez, A.; Cortiana, G.; Costa, G.; Costa, M. J.; Costanzo, D.; Cottin, G.; Cowan, G.; Cox, B. E.; Cranmer, K.; Crawley, S. J.; Cree, G.; Crépé-Renaudin, S.; Crescioli, F.; Cribbs, W. A.; Crispin Ortuzar, M.; Cristinziani, M.; Croft, V.; Crosetti, G.; Cuhadar Donszelmann, T.; Cummings, J.; Curatolo, M.; Cúth, J.; Cuthbert, C.; Czirr, H.; Czodrowski, P.; D'amen, G.; D'Auria, S.; D'Onofrio, M.; Da Cunha Sargedas De Sousa, M. J.; Da Via, C.; Dabrowski, W.; Dado, T.; Dai, T.; Dale, O.; Dallaire, F.; Dallapiccola, C.; Dam, M.; Dandoy, J. R.; Dang, N. P.; Daniells, A. C.; Dann, N. S.; Danninger, M.; Dano Hoffmann, M.; Dao, V.; Darbo, G.; Darmora, S.; Dassoulas, J.; Dattagupta, A.; Davey, W.; David, C.; Davidek, T.; Davies, M.; Davison, P.; Dawe, E.; Dawson, I.; Daya-Ishmukhametova, R. K.; De, K.; de Asmundis, R.; De Benedetti, A.; De Castro, S.; De Cecco, S.; De Groot, N.; de Jong, P.; De la Torre, H.; De Lorenzi, F.; De Maria, A.; De Pedis, D.; De Salvo, A.; De Sanctis, U.; De Santo, A.; De Vivie De Regie, J. B.; Dearnaley, W. J.; Debbe, R.; Debenedetti, C.; Dedovich, D. V.; Dehghanian, N.; Deigaard, I.; Del Gaudio, M.; Del Peso, J.; Del Prete, T.; Delgove, D.; Deliot, F.; Delitzsch, C. M.; Deliyergiyev, M.; Dell'Acqua, A.; Dell'Asta, L.; Dell'Orso, M.; Della Pietra, M.; della Volpe, D.; Delmastro, M.; Delsart, P. A.; Deluca, C.; DeMarco, D. A.; Demers, S.; Demichev, M.; Demilly, A.; Denisov, S. P.; Denysiuk, D.; Derendarz, D.; Derkaoui, J. E.; Derue, F.; Dervan, P.; Desch, K.; Deterre, C.; Dette, K.; Deviveiros, P. O.; Dewhurst, A.; Dhaliwal, S.; Di Ciaccio, A.; Di Ciaccio, L.; Di Clemente, W. K.; Di Donato, C.; Di Girolamo, A.; Di Girolamo, B.; Di Micco, B.; Di Nardo, R.; Di Simone, A.; Di Sipio, R.; Di Valentino, D.; Diaconu, C.; Diamond, M.; Dias, F. A.; Diaz, M. A.; Diehl, E. B.; Dietrich, J.; Diglio, S.; Dimitrievska, A.; Dingfelder, J.; Dita, P.; Dita, S.; Dittus, F.; Djama, F.; Djobava, T.; Djuvsland, J. I.; do Vale, M. A. B.; Dobos, D.; Dobre, M.; Doglioni, C.; Dohmae, T.; Dolejsi, J.; Dolezal, Z.; Dolgoshein, B. A.; Donadelli, M.; Donati, S.; Dondero, P.; Donini, J.; Dopke, J.; Doria, A.; Dova, M. T.; Doyle, A. T.; Drechsler, E.; Dris, M.; Du, Y.; Duarte-Campderros, J.; Duchovni, E.; Duckeck, G.; Ducu, O. A.; Duda, D.; Dudarev, A.; Duflot, L.; Duguid, L.; Dührssen, M.; Dumancic, M.; Dunford, M.; Duran Yildiz, H.; Düren, M.; Durglishvili, A.; Duschinger, D.; Dutta, B.; Dyndal, M.; Eckardt, C.; Ecker, K. M.; Edgar, R. C.; Edwards, N. C.; Eifert, T.; Eigen, G.; Einsweiler, K.; Ekelof, T.; El Kacimi, M.; Ellajosyula, V.; Ellert, M.; Elles, S.; Ellinghaus, F.; Elliot, A. A.; Ellis, N.; Elmsheuser, J.; Elsing, M.; Emeliyanov, D.; Enari, Y.; Endner, O. C.; Endo, M.; Ennis, J. S.; Erdmann, J.; Ereditato, A.; Ernis, G.; Ernst, J.; Ernst, M.; Errede, S.; Ertel, E.; Escalier, M.; Esch, H.; Escobar, C.; Esposito, B.; Etienvre, A. I.; Etzion, E.; Evans, H.; Ezhilov, A.; Fabbri, F.; Fabbri, L.; Facini, G.; Fakhrutdinov, R. M.; Falciano, S.; Falla, R. J.; Faltova, J.; Fang, Y.; Fanti, M.; Farbin, A.; Farilla, A.; Farina, C.; Farooque, T.; Farrell, S.; Farrington, S. M.; Farthouat, P.; Fassi, F.; Fassnacht, P.; Fassouliotis, D.; Faucci Giannelli, M.; Favareto, A.; Fawcett, W. J.; Fayard, L.; Fedin, O. L.; Fedorko, W.; Feigl, S.; Feligioni, L.; Feng, C.; Feng, E. J.; Feng, H.; Fenyuk, A. B.; Feremenga, L.; Fernandez Martinez, P.; Fernandez Perez, S.; Ferrando, J.; Ferrari, A.; Ferrari, P.; Ferrari, R.; Ferreira de Lima, D. E.; Ferrer, A.; Ferrere, D.; Ferretti, C.; Ferretto Parodi, A.; Fiedler, F.; Filipčič, A.; Filipuzzi, M.; Filthaut, F.; Fincke-Keeler, M.; Finelli, K. D.; Fiolhais, M. C. N.; Fiorini, L.; Firan, A.; Fischer, A.; Fischer, C.; Fischer, J.; Fisher, W. C.; Flaschel, N.; Fleck, I.; Fleischmann, P.; Fletcher, G. T.; Fletcher, R. R. M.; Flick, T.; Floderus, A.; Flores Castillo, L. R.; Flowerdew, M. J.; Forcolin, G. T.; Formica, A.; Forti, A.; Foster, A. G.; Fournier, D.; Fox, H.; Fracchia, S.; Francavilla, P.; Franchini, M.; Francis, D.; Franconi, L.; Franklin, M.; Frate, M.; Fraternali, M.; Freeborn, D.; Fressard-Batraneanu, S. M.; Friedrich, F.; Froidevaux, D.; Frost, J. A.; Fukunaga, C.; Fullana Torregrosa, E.; Fusayasu, T.; Fuster, J.; Gabaldon, C.; Gabizon, O.; Gabrielli, A.; Gabrielli, A.; Gach, G. P.; Gadatsch, S.; Gadomski, S.; Gagliardi, G.; Gagnon, L. G.; Gagnon, P.; Galea, C.; Galhardo, B.; Gallas, E. J.; Gallop, B. J.; Gallus, P.; Galster, G.; Gan, K. K.; Gao, J.; Gao, Y.; Gao, Y. S.; Garay Walls, F. M.; García, C.; García Navarro, J. E.; Garcia-Sciveres, M.; Gardner, R. W.; Garelli, N.; Garonne, V.; Gascon Bravo, A.; Gatti, C.; Gaudiello, A.; Gaudio, G.; Gaur, B.; Gauthier, L.; Gavrilenko, I. L.; Gay, C.; Gaycken, G.; Gazis, E. N.; Gecse, Z.; Gee, C. N. P.; Geich-Gimbel, Ch.; Geisler, M. P.; Gemme, C.; Genest, M. H.; Geng, C.; Gentile, S.; George, S.; Gerbaudo, D.; Gershon, A.; Ghasemi, S.; Ghazlane, H.; Ghneimat, M.; Giacobbe, B.; Giagu, S.; Giannetti, P.; Gibbard, B.; Gibson, S. M.; Gignac, M.; Gilchriese, M.; Gillam, T. P. S.; Gillberg, D.; Gilles, G.; Gingrich, D. M.; Giokaris, N.; Giordani, M. P.; Giorgi, F. M.; Giorgi, F. M.; Giraud, P. F.; Giromini, P.; Giugni, D.; Giuli, F.; Giuliani, C.; Giulini, M.; Gjelsten, B. K.; Gkaitatzis, S.; Gkialas, I.; Gkougkousis, E. L.; Gladilin, L. K.; Glasman, C.; Glatzer, J.; Glaysher, P. C. F.; Glazov, A.; Goblirsch-Kolb, M.; Godlewski, J.; Goldfarb, S.; Golling, T.; Golubkov, D.; Gomes, A.; Gonçalo, R.; Goncalves Pinto Firmino Da Costa, J.; Gonella, L.; Gongadze, A.; González de la Hoz, S.; Gonzalez Parra, G.; Gonzalez-Sevilla, S.; Goossens, L.; Gorbounov, P. A.; Gordon, H. A.; Gorelov, I.; Gorini, B.; Gorini, E.; Gorišek, A.; Gornicki, E.; Goshaw, A. T.; Gössling, C.; Gostkin, M. I.; Goudet, C. R.; Goujdami, D.; Goussiou, A. G.; Govender, N.; Gozani, E.; Graber, L.; Grabowska-Bold, I.; Gradin, P. O. J.; Grafström, P.; Gramling, J.; Gramstad, E.; Grancagnolo, S.; Gratchev, V.; Gray, H. M.; Graziani, E.; Greenwood, Z. D.; Grefe, C.; Gregersen, K.; Gregor, I. M.; Grenier, P.; Grevtsov, K.; Griffiths, J.; Grillo, A. A.; Grimm, K.; Grinstein, S.; Gris, Ph.; Grivaz, J.-F.; Groh, S.; Grohs, J. P.; Gross, E.; Grosse-Knetter, J.; Grossi, G. C.; Grout, Z. J.; Guan, L.; Guan, W.; Guenther, J.; Guescini, F.; Guest, D.; Gueta, O.; Guido, E.; Guillemin, T.; Guindon, S.; Gul, U.; Gumpert, C.; Guo, J.; Guo, Y.; Gupta, S.; Gustavino, G.; Gutierrez, P.; Gutierrez Ortiz, N. G.; Gutschow, C.; Guyot, C.; Gwenlan, C.; Gwilliam, C. B.; Haas, A.; Haber, C.; Hadavand, H. K.; Haddad, N.; Hadef, A.; Haefner, P.; Hageböck, S.; Hajduk, Z.; Hakobyan, H.; Haleem, M.; Haley, J.; Halladjian, G.; Hallewell, G. D.; Hamacher, K.; Hamal, P.; Hamano, K.; Hamilton, A.; Hamity, G. N.; Hamnett, P. G.; Han, L.; Hanagaki, K.; Hanawa, K.; Hance, M.; Haney, B.; Hanke, P.; Hanna, R.; Hansen, J. B.; Hansen, J. D.; Hansen, M. C.; Hansen, P. H.; Hara, K.; Hard, A. S.; Harenberg, T.; Hariri, F.; Harkusha, S.; Harrington, R. D.; Harrison, P. F.; Hartjes, F.; Hartmann, N. M.; Hasegawa, M.; Hasegawa, Y.; Hasib, A.; Hassani, S.; Haug, S.; Hauser, R.; Hauswald, L.; Havranek, M.; Hawkes, C. M.; Hawkings, R. J.; Hayden, D.; Hays, C. P.; Hays, J. M.; Hayward, H. S.; Haywood, S. J.; Head, S. J.; Heck, T.; Hedberg, V.; Heelan, L.; Heim, S.; Heim, T.; Heinemann, B.; Heinrich, J. J.; Heinrich, L.; Heinz, C.; Hejbal, J.; Helary, L.; Hellman, S.; Helsens, C.; Henderson, J.; Henderson, R. C. W.; Heng, Y.; Henkelmann, S.; Henriques Correia, A. M.; Henrot-Versille, S.; Herbert, G. H.; Hernández Jiménez, Y.; Herten, G.; Hertenberger, R.; Hervas, L.; Hesketh, G. G.; Hessey, N. P.; Hetherly, J. W.; Hickling, R.; Higón-Rodriguez, E.; Hill, E.; Hill, J. C.; Hiller, K. H.; Hillier, S. J.; Hinchliffe, I.; Hines, E.; Hinman, R. R.; Hirose, M.; Hirschbuehl, D.; Hobbs, J.; Hod, N.; Hodgkinson, M. C.; Hodgson, P.; Hoecker, A.; Hoeferkamp, M. R.; Hoenig, F.; Hohlfeld, M.; Hohn, D.; Holmes, T. R.; Homann, M.; Hong, T. M.; Hooberman, B. H.; Hopkins, W. H.; Horii, Y.; Horton, A. J.; Hostachy, J.-Y.; Hou, S.; Hoummada, A.; Howarth, J.; Hrabovsky, M.; Hristova, I.; Hrivnac, J.; Hryn'ova, T.; Hrynevich, A.; Hsu, C.; Hsu, P. J.; Hsu, S.-C.; Hu, D.; Hu, Q.; Huang, Y.; Hubacek, Z.; Hubaut, F.; Huegging, F.; Huffman, T. B.; Hughes, E. W.; Hughes, G.; Huhtinen, M.; Hülsing, T. 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J.; Ulrich, R.; Wagner-Kuhr, J.; Wayand, S.; Weber, M.; Weiler, T.; Williamson, S.; Wöhrmann, C.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Topsis-Giotis, I.; Agapitos, A.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Tziaferi, E.; Evangelou, I.; Flouris, G.; Foudas, C.; Kokkas, P.; Loukas, N.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Filipovic, N.; Bencze, G.; Hajdu, C.; Hidas, P.; Horvath, D.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. J.; Beni, N.; Czellar, S.; Karancsi, J.; Molnar, J.; Szillasi, Z.; Bartók, M.; Makovec, A.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Bahinipati, S.; Choudhury, S.; Mal, P.; Mandal, K.; Nayak, A.; Sahoo, D. K.; Sahoo, N.; Swain, S. K.; Bansal, S.; Beri, S. B.; Bhatnagar, V.; Chawla, R.; Gupta, R.; Bhawandeep, U.; Kalsi, A. K.; Kaur, A.; Kaur, M.; Kumar, R.; Mehta, A.; Mittal, M.; Singh, J. B.; Walia, G.; Kumar, Ashok; Bhardwaj, A.; Choudhary, B. C.; Garg, R. 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M.; Fahim, A.; Khakzad, M.; Mohammadi Najafabadi, M.; Naseri, M.; Paktinat Mehdiabadi, S.; Rezaei Hosseinabadi, F.; Safarzadeh, B.; Zeinali, M.; Felcini, M.; Grunewald, M.; Abbrescia, M.; Calabria, C.; Caputo, C.; Colaleo, A.; Creanza, D.; Cristella, L.; De Filippis, N.; De Palma, M.; Fiore, L.; Iaselli, G.; Maggi, G.; Maggi, M.; Miniello, G.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Ranieri, A.; Selvaggi, G.; Silvestris, L.; Venditti, R.; Abbiendi, G.; Battilana, C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Brigliadori, L.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Chhibra, S. S.; Codispoti, G.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Grandi, C.; Guiducci, L.; Marcellini, S.; Masetti, G.; Montanari, A.; Navarria, F. L.; Perrotta, A.; Rossi, A. M.; Rovelli, T.; Siroli, G. 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M.; Lanza, G.; Lista, L.; Meola, S.; Merola, M.; Paolucci, P.; Sciacca, C.; Thyssen, F.; Azzi, P.; Bacchetta, N.; Benato, L.; Bisello, D.; Boletti, A.; Carlin, R.; Carvalho Antunes De Oliveira, A.; Checchia, P.; Dall'Osso, M.; De Castro Manzano, P.; Dorigo, T.; Dosselli, U.; Gasparini, F.; Gasparini, U.; Gozzelino, A.; Lacaprara, S.; Margoni, M.; Meneguzzo, A. T.; Pazzini, J.; Pozzobon, N.; Ronchese, P.; Simonetto, F.; Torassa, E.; Tosi, M.; Zanetti, M.; Zotto, P.; Zucchetta, A.; Zumerle, G.; Braghieri, A.; Magnani, A.; Montagna, P.; Ratti, S. P.; Re, V.; Riccardi, C.; Salvini, P.; Vai, I.; Vitulo, P.; Alunni Solestizi, L.; Bilei, G. M.; Ciangottini, D.; Fanò, L.; Lariccia, P.; Leonardi, R.; Mantovani, G.; Menichelli, M.; Saha, A.; Santocchia, A.; Androsov, K.; Azzurri, P.; Bagliesi, G.; Bernardini, J.; Boccali, T.; Castaldi, R.; Ciocci, M. A.; Dell'Orso, R.; Donato, S.; Fedi, G.; Giassi, A.; Grippo, M. T.; Ligabue, F.; Lomtadze, T.; Martini, L.; Messineo, A.; Palla, F.; Rizzi, A.; SavoyNavarro, A.; Spagnolo, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Barone, L.; Cavallari, F.; Cipriani, M.; D'imperio, G.; Del Re, D.; Diemoz, M.; Gelli, S.; Jorda, C.; Longo, E.; Margaroli, F.; Meridiani, P.; Organtini, G.; Paramatti, R.; Preiato, F.; Rahatlou, S.; Rovelli, C.; Santanastasio, F.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bartosik, N.; Bellan, R.; Biino, C.; Cartiglia, N.; Costa, M.; Covarelli, R.; Degano, A.; Demaria, N.; Finco, L.; Kiani, B.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Monteil, E.; Obertino, M. M.; Pacher, L.; Pastrone, N.; Pelliccioni, M.; Pinna Angioni, G. L.; Ravera, F.; Romero, A.; Ruspa, M.; Sacchi, R.; Shchelina, K.; Sola, V.; Solano, A.; Staiano, A.; Traczyk, P.; Belforte, S.; Candelise, V.; Casarsa, M.; Cossutti, F.; Della Ricca, G.; La Licata, C.; Schizzi, A.; Zanetti, A.; Kim, D. H.; Kim, G. N.; Kim, M. S.; Lee, S.; Lee, S. W.; Oh, Y. D.; Sekmen, S.; Son, D. C.; Yang, Y. C.; Kim, H.; Lee, A.; Brochero Cifuentes, J. A.; Kim, T. J.; Cho, S.; Choi, S.; Go, Y.; Gyun, D.; Ha, S.; Hong, B.; Jo, Y.; Kim, Y.; Lee, B.; Lee, K.; Lee, K. S.; Lee, S.; Lim, J.; Park, S. K.; Roh, Y.; Almond, J.; Kim, J.; Oh, S. B.; Seo, S. h.; Yang, U. K.; Yoo, H. D.; Yu, G. B.; Choi, M.; Kim, H.; Kim, H.; Kim, J. H.; Lee, J. S. H.; Park, I. C.; Ryu, G.; Ryu, M. S.; Choi, Y.; Goh, J.; Kim, D.; Kwon, E.; Lee, J.; Yu, I.; Dudenas, V.; Juodagalvis, A.; Vaitkus, J.; Ahmed, I.; Ibrahim, Z. A.; Komaragiri, J. R.; Md Ali, M. A. B.; Mohamad Idris, F.; Wan Abdullah, W. A. T.; Yusli, M. N.; Zolkapli, Z.; Casimiro Linares, E.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Heredia-De La Cruz, I.; Hernandez-Almada, A.; Lopez-Fernandez, R.; Mejia Guisao, J.; Sanchez-Hernandez, A.; Carrillo Moreno, S.; Vazquez Valencia, F.; Pedraza, I.; Salazar Ibarguen, H. A.; Uribe Estrada, C.; Morelos Pineda, A.; Krofcheck, D.; Butler, P. H.; Ahmad, A.; Ahmad, M.; Hassan, Q.; Hoorani, H. R.; Khan, W. A.; Khurshid, T.; Qazi, S.; Waqas, M.; Bialkowska, H.; Bluj, M.; Boimska, B.; Frueboes, T.; Górski, M.; Kazana, M.; Nawrocki, K.; Romanowska-Rybinska, K.; Szleper, M.; Zalewski, P.; Bunkowski, K.; Byszuk, A.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Misiura, M.; Olszewski, M.; Walczak, M.; Bargassa, P.; Beirão Da Cruz E Silva, C.; Di Francesco, A.; Faccioli, P.; Ferreira Parracho, P. G.; Gallinaro, M.; Hollar, J.; Leonardo, N.; Lloret Iglesias, L.; Nemallapudi, M. V.; Rodrigues Antunes, J.; Seixas, J.; Toldaiev, O.; Vadruccio, D.; Varela, J.; Vischia, P.; Afanasiev, S.; Gavrilenko, M.; Golutvin, I.; Gorbunov, I.; Karjavin, V.; Kozlov, G.; Lanev, A.; Malakhov, A.; Matveev, V.; Moisenz, P.; Palichik, V.; Perelygin, V.; Savina, M.; Shmatov, S.; Shulha, S.; Skatchkov, N.; Smirnov, V.; Voytishin, N.; Zarubin, A.; Chtchipounov, L.; Golovtsov, V.; Ivanov, Y.; Kim, V.; Kuznetsova, E.; Murzin, V.; Oreshkin, V.; Sulimov, V.; Vorobyev, A.; Andreev, Yu.; Dermenev, A.; Gninenko, S.; Golubev, N.; Karneyeu, A.; Kirsanov, M.; Krasnikov, N.; Pashenkov, A.; Tlisov, D.; Toropin, A.; Epshteyn, V.; Gavrilov, V.; Lychkovskaya, N.; Popov, V.; Pozdnyakov, I.; Safronov, G.; Spiridonov, A.; Toms, M.; Vlasov, E.; Zhokin, A.; Chistov, R.; Markin, O.; Rusinov, V.; Andreev, V.; Azarkin, M.; Dremin, I.; Kirakosyan, M.; Leonidov, A.; Rusakov, S. V.; Terkulov, A.; Baskakov, A.; Belyaev, A.; Boos, E.; Bunichev, V.; Dubinin, M.; Dudko, L.; Ershov, A.; Gribushin, A.; Klyukhin, V.; Kodolova, O.; Lokhtin, I.; Miagkov, I.; Obraztsov, S.; Petrushanko, S.; Savrin, V.; Azhgirey, I.; Bayshev, I.; Bitioukov, S.; Elumakhov, D.; Kachanov, V.; Kalinin, A.; Konstantinov, D.; Krychkine, V.; Petrov, V.; Ryutin, R.; Sobol, A.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Adzic, P.; Cirkovic, P.; Devetak, D.; Milosevic, J.; Rekovic, V.; Alcaraz Maestre, J.; Calvo, E.; Cerrada, M.; Chamizo Llatas, M.; Colino, N.; De La Cruz, B.; Delgado Peris, A.; Escalante Del Valle, A.; Fernandez Bedoya, C.; Fernández Ramos, J. P.; Flix, J.; Fouz, M. C.; Garcia-Abia, P.; Gonzalez Lopez, O.; Goy Lopez, S.; Hernandez, J. M.; Josa, M. I.; Navarro De Martino, E.; Pérez-Calero Yzquierdo, A.; Puerta Pelayo, J.; Quintario Olmeda, A.; Redondo, I.; Romero, L.; Soares, M. S.; de Trocóniz, J. F.; Missiroli, M.; Moran, D.; Cuevas, J.; Fernandez Menendez, J.; Gonzalez Caballero, I.; Palencia Cortezon, E.; Sanchez Cruz, S.; Vizan Garcia, J. M.; Cabrillo, I. J.; Calderon, A.; Castiñeiras De Saa, J. R.; Curras, E.; Fernandez, M.; Garcia-Ferrero, J.; Gomez, G.; Lopez Virto, A.; Marco, J.; Martinez Rivero, C.; Matorras, F.; Piedra Gomez, J.; Rodrigo, T.; Ruiz-Jimeno, A.; Scodellaro, L.; Trevisani, N.; Vila, I.; Vilar Cortabitarte, R.; Abbaneo, D.; Auffray, E.; Auzinger, G.; Bachtis, M.; Baillon, P.; Ball, A. H.; Barney, D.; Bloch, P.; Bocci, A.; Bonato, A.; Botta, C.; Camporesi, T.; Castello, R.; Cepeda, M.; Cerminara, G.; D'Alfonso, M.; d'Enterria, D.; Dabrowski, A.; Daponte, V.; David, A.; De Gruttola, M.; De Guio, F.; De Roeck, A.; Di Marco, E.; Dobson, M.; Dordevic, M.; Dorney, B.; du Pree, T.; Duggan, D.; Dünser, M.; Dupont, N.; Elliott-Peisert, A.; Fartoukh, S.; Franzoni, G.; Fulcher, J.; Funk, W.; Gigi, D.; Gill, K.; Girone, M.; Glege, F.; Gundacker, S.; Guthoff, M.; Hammer, J.; Harris, P.; Hegeman, J.; Innocente, V.; Janot, P.; Kirschenmann, H.; Knünz, V.; Kortelainen, M. J.; Kousouris, K.; Krammer, M.; Lecoq, P.; Lourenço, C.; Lucchini, M. T.; Magini, N.; Malgeri, L.; Mannelli, M.; Martelli, A.; Meijers, F.; Mersi, S.; Meschi, E.; Moortgat, F.; Morovic, S.; Mulders, M.; Neugebauer, H.; Orfanelli, S.; Orsini, L.; Pape, L.; Perez, E.; Peruzzi, M.; Petrilli, A.; Petrucciani, G.; Pfeiffer, A.; Pierini, M.; Racz, A.; Reis, T.; Rolandi, G.; Rovere, M.; Ruan, M.; Sakulin, H.; Sauvan, J. B.; Schäfer, C.; Schwick, C.; Seidel, M.; Sharma, A.; Silva, P.; Simon, M.; Sphicas, P.; Steggemann, J.; Stoye, M.; Takahashi, Y.; Treille, D.; Triossi, A.; Tsirou, A.; Veckalns, V.; Veres, G. I.; Wardle, N.; Zagozdzinska, A.; Zeuner, W. D.; Bertl, W.; Deiters, K.; Erdmann, W.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; Langenegger, U.; Rohe, T.; Bachmair, F.; Bäni, L.; Bianchini, L.; Casal, B.; Dissertori, G.; Dittmar, M.; Donegà, M.; Eller, P.; Grab, C.; Heidegger, C.; Hits, D.; Hoss, J.; Kasieczka, G.; Lecomte, P.; Lustermann, W.; Mangano, B.; Marionneau, M.; Martinez Ruiz del Arbol, P.; Masciovecchio, M.; Meinhard, M. T.; Meister, D.; Micheli, F.; Musella, P.; Nessi-Tedaldi, F.; Pandolfi, F.; Pata, J.; Pauss, F.; Perrin, G.; Perrozzi, L.; Quittnat, M.; Rossini, M.; Schönenberger, M.; Starodumov, A.; Takahashi, M.; Tavolaro, V. R.; Theofilatos, K.; Wallny, R.; Aarrestad, T. K.; Amsler, C.; Caminada, L.; Canelli, M. F.; Chiochia, V.; De Cosa, A.; Galloni, C.; Hinzmann, A.; Hreus, T.; Kilminster, B.; Lange, C.; Ngadiuba, J.; Pinna, D.; Rauco, G.; Robmann, P.; Salerno, D.; Yang, Y.; Doan, T. H.; Jain, Sh.; Khurana, R.; Konyushikhin, M.; Kuo, C. M.; Lin, W.; Lu, Y. J.; Pozdnyakov, A.; Yu, S. S.; Kumar, Arun; Chang, P.; Chang, Y. H.; Chang, Y. W.; Chao, Y.; Chen, K. F.; Chen, P. H.; Dietz, C.; Fiori, F.; Hsiung, Y.; Liu, Y. F.; Lu, R.-S.; Miñano Moya, M.; Paganis, E.; Psallidas, A.; Tsai, J. f.; Tzeng, Y. M.; Asavapibhop, B.; Singh, G.; Srimanobhas, N.; Suwonjandee, N.; Adiguzel, A.; Bakirci, M. N.; Damarseckin, S.; Demiroglu, Z. S.; Dozen, C.; Dumanoglu, I.; Girgis, S.; Gokbulut, G.; Guler, Y.; Gurpinar, E.; Hos, I.; Kangal, E. E.; Kayis Topaksu, A.; Onengut, G.; Ozdemir, K.; Sunar Cerci, D.; Tali, B.; Zorbilmez, C.; Bilin, B.; Bilmis, S.; Isildak, B.; Karapinar, G.; Yalvac, M.; Zeyrek, M.; Gülmez, E.; Kaya, M.; Kaya, O.; Yetkin, E. A.; Yetkin, T.; Cakir, A.; Cankocak, K.; Sen, S.; Vardarlı, F. 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M.; Richards, A.; Rose, A.; Seez, C.; Tapper, A.; Uchida, K.; Vazquez Acosta, M.; Virdee, T.; Zenz, S. C.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Leslie, D.; Reid, I. D.; Symonds, P.; Teodorescu, L.; Turner, M.; Borzou, A.; Call, K.; Dittmann, J.; Hatakeyama, K.; Liu, H.; Pastika, N.; Charaf, O.; Cooper, S. I.; Henderson, C.; Rumerio, P.; Arcaro, D.; Avetisyan, A.; Bose, T.; Gastler, D.; Rankin, D.; Richardson, C.; Rohlf, J.; Sulak, L.; Zou, D.; Benelli, G.; Berry, E.; Cutts, D.; Ferapontov, A.; Garabedian, A.; Hakala, J.; Heintz, U.; Jesus, O.; Laird, E.; Landsberg, G.; Mao, Z.; Narain, M.; Piperov, S.; Sagir, S.; Spencer, E.; Syarif, R.; Breedon, R.; Breto, G.; Burns, D.; Calderon De La Barca Sanchez, M.; Chauhan, S.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Erbacher, R.; Flores, C.; Funk, G.; Gardner, M.; Ko, W.; Lander, R.; Mclean, C.; Mulhearn, M.; Pellett, D.; Pilot, J.; Ricci-Tam, F.; Shalhout, S.; Smith, J.; Squires, M.; Stolp, D.; Tripathi, M.; Wilbur, S.; Yohay, R.; Cousins, R.; Everaerts, P.; Florent, A.; Hauser, J.; Ignatenko, M.; Saltzberg, D.; Takasugi, E.; Valuev, V.; Weber, M.; Burt, K.; Clare, R.; Ellison, J.; Gary, J. W.; Hanson, G.; Heilman, J.; Jandir, P.; Kennedy, E.; Lacroix, F.; Long, O. R.; Malberti, M.; Olmedo Negrete, M.; Paneva, M. I.; Shrinivas, A.; Wei, H.; Wimpenny, S.; Yates, B. R.; Branson, J. G.; Cerati, G. B.; Cittolin, S.; D'Agnolo, R. T.; Derdzinski, M.; Gerosa, R.; Holzner, A.; Kelley, R.; Klein, D.; Letts, J.; Macneill, I.; Olivito, D.; Padhi, S.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Tadel, M.; Vartak, A.; Wasserbaech, S.; Welke, C.; Wood, J.; Würthwein, F.; Yagil, A.; Zevi Della Porta, G.; Bhandari, R.; Bradmiller-Feld, J.; Campagnari, C.; Dishaw, A.; Dutta, V.; Flowers, K.; Franco Sevilla, M.; Geffert, P.; George, C.; Golf, F.; Gouskos, L.; Gran, J.; Heller, R.; Incandela, J.; Mccoll, N.; Mullin, S. D.; Ovcharova, A.; Richman, J.; Stuart, D.; Suarez, I.; West, C.; Yoo, J.; Anderson, D.; Apresyan, A.; Bendavid, J.; Bornheim, A.; Bunn, J.; Chen, Y.; Duarte, J.; Mott, A.; Newman, H. B.; Pena, C.; Spiropulu, M.; Vlimant, J. R.; Xie, S.; Zhu, R. Y.; Andrews, M. B.; Azzolini, V.; Calamba, A.; Carlson, B.; Ferguson, T.; Paulini, M.; Russ, J.; Sun, M.; Vogel, H.; Vorobiev, I.; Cumalat, J. P.; Ford, W. T.; Jensen, F.; Johnson, A.; Krohn, M.; Mulholland, T.; Stenson, K.; Wagner, S. R.; Alexander, J.; Chaves, J.; Chu, J.; Dittmer, S.; Mirman, N.; Nicolas Kaufman, G.; Patterson, J. R.; Rinkevicius, A.; Ryd, A.; Skinnari, L.; Sun, W.; Tan, S. M.; Tao, Z.; Thom, J.; Tucker, J.; Wittich, P.; Winn, D.; Abdullin, S.; Albrow, M.; Apollinari, G.; Banerjee, S.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bolla, G.; Burkett, K.; Butler, J. N.; Cheung, H. W. K.; Chlebana, F.; Cihangir, S.; Cremonesi, M.; Elvira, V. D.; Fisk, I.; Freeman, J.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Hare, D.; Harris, R. M.; Hasegawa, S.; Hirschauer, J.; Hu, Z.; Jayatilaka, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kreis, B.; Lammel, S.; Linacre, J.; Lincoln, D.; Lipton, R.; Liu, T.; Lopes De Sá, R.; Lykken, J.; Maeshima, K.; Marraffino, J. M.; Maruyama, S.; Mason, D.; McBride, P.; Merkel, P.; Mrenna, S.; Nahn, S.; Newman-Holmes, C.; O'Dell, V.; Pedro, K.; Prokofyev, O.; Rakness, G.; Ristori, L.; SextonKennedy, E.; Soha, A.; Spalding, W. J.; Spiegel, L.; Stoynev, S.; Strobbe, N.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vernieri, C.; Verzocchi, M.; Vidal, R.; Wang, M.; Weber, H. A.; Whitbeck, A.; Acosta, D.; Avery, P.; Bortignon, P.; Bourilkov, D.; Brinkerhoff, A.; Carnes, A.; Carver, M.; Curry, D.; Das, S.; Field, R. D.; Furic, I. K.; Konigsberg, J.; Korytov, A.; Ma, P.; Matchev, K.; Mei, H.; Milenovic, P.; Mitselmakher, G.; Rank, D.; Shchutska, L.; Sperka, D.; Thomas, L.; Wang, J.; Wang, S.; Yelton, J.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Ackert, A.; Adams, J. R.; Adams, T.; Askew, A.; Bein, S.; Diamond, B.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Khatiwada, A.; Prosper, H.; Santra, A.; Weinberg, M.; Baarmand, M. M.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Kalakhety, H.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Bucinskaite, I.; Cavanaugh, R.; Evdokimov, O.; Gauthier, L.; Gerber, C. E.; Hofman, D. J.; Kurt, P.; O'Brien, C.; Sandoval Gonzalez, I. D.; Turner, P.; Varelas, N.; Wu, Z.; Zakaria, M.; Zhang, J.; Bilki, B.; Clarida, W.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Snyder, C.; Tiras, E.; Wetzel, J.; Yi, K.; Anderson, I.; Blumenfeld, B.; Cocoros, A.; Eminizer, N.; Fehling, D.; Feng, L.; Gritsan, A. V.; Maksimovic, P.; Osherson, M.; Roskes, J.; Sarica, U.; Swartz, M.; Xiao, M.; Xin, Y.; You, C.; Al-bataineh, A.; Baringer, P.; Bean, A.; Bowen, J.; Bruner, C.; Castle, J.; Kenny, R. P.; Kropivnitskaya, A.; Majumder, D.; Mcbrayer, W.; Murray, M.; Sanders, S.; Stringer, R.; Tapia Takaki, J. D.; Wang, Q.; Ivanov, A.; Kaadze, K.; Khalil, S.; Makouski, M.; Maravin, Y.; Mohammadi, A.; Saini, L. K.; Skhirtladze, N.; Toda, S.; Lange, D.; Rebassoo, F.; Wright, D.; Anelli, C.; Baden, A.; Baron, O.; Belloni, A.; Calvert, B.; Eno, S. C.; Ferraioli, C.; Gomez, J. A.; Hadley, N. J.; Jabeen, S.; Kellogg, R. G.; Kolberg, T.; Kunkle, J.; Lu, Y.; Mignerey, A. C.; Shin, Y. H.; Skuja, A.; Tonjes, M. B.; Tonwar, S. C.; Apyan, A.; Barbieri, R.; Baty, A.; Bi, R.; Bierwagen, K.; Brandt, S.; Busza, W.; Cali, I. A.; Demiragli, Z.; Di Matteo, L.; Gomez Ceballos, G.; Goncharov, M.; Gulhan, D.; Hsu, D.; Iiyama, Y.; Innocenti, G. M.; Klute, M.; Kovalskyi, D.; Krajczar, K.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Marini, A. C.; Mcginn, C.; Mironov, C.; Narayanan, S.; Niu, X.; Paus, C.; Roland, C.; Roland, G.; Salfeld-Nebgen, J.; Stephans, G. S. F.; Sumorok, K.; Tatar, K.; Varma, M.; Velicanu, D.; Veverka, J.; Wang, J.; Wang, T. W.; Wyslouch, B.; Yang, M.; Zhukova, V.; Benvenuti, A. C.; Chatterjee, R. M.; Dahmes, B.; Evans, A.; Finkel, A.; Gude, A.; Hansen, P.; Kalafut, S.; Kao, S. C.; Klapoetke, K.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Tambe, N.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bartek, R.; Bloom, K.; Bose, S.; Claes, D. R.; Dominguez, A.; Fangmeier, C.; Gonzalez Suarez, R.; Kamalieddin, R.; Knowlton, D.; Kravchenko, I.; Meier, F.; Monroy, J.; Siado, J. E.; Snow, G. R.; Stieger, B.; Alyari, M.; Dolen, J.; George, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Kaisen, J.; Kharchilava, A.; Kumar, A.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Baumgartel, D.; Chasco, M.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Teixeira De Lima, R.; Trocino, D.; Wang, R.-J.; Wood, D.; Bhattacharya, S.; Hahn, K. A.; Kubik, A.; Low, J. F.; Mucia, N.; Odell, N.; Pollack, B.; Schmitt, M. H.; Sung, K.; Trovato, M.; Velasco, M.; Dev, N.; Hildreth, M.; Hurtado Anampa, K.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Rupprecht, N.; Smith, G.; Taroni, S.; Valls, N.; Wayne, M.; Wolf, M.; Woodard, A.; Alimena, J.; Antonelli, L.; Brinson, J.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Francis, B.; Hart, A.; Hill, C.; Hughes, R.; Ji, W.; Liu, B.; Luo, W.; Puigh, D.; Rodenburg, M.; Winer, B. L.; Wulsin, H. W.; Cooperstein, S.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Luo, J.; Marlow, D.; Medvedeva, T.; Mooney, M.; Olsen, J.; Palmer, C.; Piroué, P.; Stickland, D.; Tully, C.; Zuranski, A.; Malik, S.; Barker, A.; Barnes, V. E.; Benedetti, D.; Folgueras, S.; Gutay, L.; Jha, M. K.; Jones, M.; Jung, A. W.; Jung, K.; Miller, D. H.; Neumeister, N.; Radburn-Smith, B. C.; Shi, X.; Sun, J.; Svyatkovskiy, A.; Wang, F.; Xie, W.; Xu, L.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Chen, Z.; Ecklund, K. M.; Geurts, F. J. M.; Guilbaud, M.; Li, W.; Michlin, B.; Northup, M.; Padley, B. P.; Redjimi, R.; Roberts, J.; Rorie, J.; Tu, Z.; Zabel, J.; Betchart, B.; Bodek, A.; de Barbaro, P.; Demina, R.; Duh, Y. t.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Han, J.; Hindrichs, O.; Khukhunaishvili, A.; Lo, K. H.; Tan, P.; Verzetti, M.; Chou, J. P.; Contreras-Campana, E.; Gershtein, Y.; Gómez Espinosa, T. A.; Halkiadakis, E.; Heindl, M.; Hidas, D.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Kyriacou, S.; Lath, A.; Nash, K.; Saka, H.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Foerster, M.; Heideman, J.; Riley, G.; Rose, K.; Spanier, S.; Thapa, K.; Bouhali, O.; Castaneda Hernandez, A.; Celik, A.; Dalchenko, M.; De Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Juska, E.; Kamon, T.; Krutelyov, V.; Mueller, R.; Pakhotin, Y.; Patel, R.; Perloff, A.; Perniè, L.; Rathjens, D.; Rose, A.; Safonov, A.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Cowden, C.; Damgov, J.; Dragoiu, C.; Dudero, P. R.; Faulkner, J.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Undleeb, S.; Volobouev, I.; Wang, Z.; Delannoy, A. G.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Melo, A.; Ni, H.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Barria, P.; Cox, B.; Goodell, J.; Hirosky, R.; Ledovskoy, A.; Li, H.; Neu, C.; Sinthuprasith, T.; Sun, X.; Wang, Y.; Wolfe, E.; Xia, F.; Clarke, C.; Harr, R.; Karchin, P. E.; Lamichhane, P.; Sturdy, J.; Belknap, D. A.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Ojalvo, I.; Perry, T.; Pierro, G. A.; Polese, G.; Ruggles, T.; Savin, A.; Sharma, A.; Smith, N.; Smith, W. H.; Taylor, D.; Verwilligen, P.; Woods, N.

2016-08-01

Combined ATLAS and CMS measurements of the Higgs boson production and decay rates, as well as constraints on its couplings to vector bosons and fermions, are presented. The combination is based on the analysis of five production processes, namely gluon fusion, vector boson fusion, and associated production with a W or a Z boson or a pair of top quarks, and of the six decay modes H → ZZ, W W , γγ , ττ, bb, and μμ. All results are reported assuming a value of 125 .09 GeV for the Higgs boson mass, the result of the combined measurement by the ATLAS and CMS experiments. The analysis uses the CERN LHC proton-proton collision data recorded by the ATLAS and CMS experiments in 2011 and 2012, corresponding to integrated luminosities per experiment of approximately 5 fb-1 at √{s}=7 TeV and 20 fb-1 at √{s}=8 TeV. The Higgs boson production and decay rates measured by the two experiments are combined within the context of three generic parameterisations: two based on cross sections and branching fractions, and one on ratios of coupling modifiers. Several interpretations of the measurements with more model-dependent parameterisations are also given. The combined signal yield relative to the Standard Model prediction is measured to be 1 .09 ± 0 .11. The combined measurements lead to observed significances for the vector boson fusion production process and for the H → ττ decay of 5 .4 and 5 .5 standard deviations, respectively. The data are consistent with the Standard Model predictions for all parameterisations considered. [Figure not available: see fulltext.][Figure not available: see fulltext.

Relationship between probability of future shoulder arthroplasty and outcomes of arthroscopic debridement in patients with advanced osteoarthritis of glenohumeral joint.

PubMed

Henry, Patrick; Razmjou, Helen; Dwyer, Tim; Slade Shantz, Jesse A; Holtby, Richard

2015-10-05

Arthroscopic glenohumeral debridement for symptom control has shown promising short term results in the young active population, when arthroplasty may not be a practical option due to the recommended activity restrictions, potential for complications and/or early wear, and a need for revision. The purpose of this study was twofold: 1) to examine the impact of arthroscopic debridement with or without subacromial decompression on clinical outcomes in patients with severe glenohumeral osteoarthritis (OA), and 2) to explore the differences in post-debridement outcomes between patients who eventually progressed to arthroplasty vs. those who did not. The role of an active worker's compensation claim was examined. Prospectively collected data of patients who were not good candidates for shoulder arthroplasty and had subsequently undergone arthroscopic shoulder debridement were used for analysis. Disability was measured using the relative Constant-Murley score (CMS), the American Shoulder and Elbow Surgeon's (ASES) assessment form, pain free range of motion (ROM), and strength. Fifty-six patients were included in the final analysis. Eighteen (32 %) patients underwent arthroplasty surgery (arthroplasty group) over a period of 11 years. The arthroplasty group was comparable with the non-arthroplasty group prior to debridement but was more disabled at post-debridement surgery follow-up, functioning at less than 50 % of normal based on ASES, relative CMS, and active painfree ROM. In the multivariable analysis, the post-debridement relative CMS was affected by having a compensation claim and having a future arthroplasty. Arthroscopic debridement improved clinical outcome in 68 % of patients suffering from advanced OA of glenohumeral joint. Having less than 50 % of normal score in ASES, relative CMS and painfree ROM post- debridement within a period of two years may be an indication for future arthroplasty. Role of worker's compensation claims should not be underestimated.

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...

Performance of photon reconstruction and identification with the CMS detector in proton-proton collisions at √s = 8 TeV

DOE PAGES

Khachatryan, Vardan

2015-08-10

A description is provided of the performance of the CMS detector for photon reconstruction and identification in proton-proton collisions at a centre-of-mass energy of 8 TeV at the CERN LHC. Details are given on the reconstruction of photons from energy deposits in the electromagnetic calorimeter (ECAL) and the extraction of photon energy estimates. Furthermore, the reconstruction of electron tracks from photons that convert to electrons in the CMS tracker is also described, as is the optimization of the photon energy reconstruction and its accurate modelling in simulation, in the analysis of the Higgs boson decay into two photons. In themore » barrel section of the ECAL, an energy resolution of about 1% is achieved for unconverted or late-converting photons from H → γγ decays. Furthermore, different photon identification methods are discussed and their corresponding selection efficiencies in data are compared with those found in simulated events.« less

Analysis of the Laser Calibration System for the CMS HCAL at CERN's Large Hadron Collider

NASA Astrophysics Data System (ADS)

Lebolo, Luis

2005-11-01

The European Organization for Nuclear Physics' (CERN) Large Hadron Collider uses the Compact Muon Solenoid (CMS) detector to measure collision products from proton-proton interactions. CMS uses a hadron calorimeter (HCAL) to measure the energy and position of quarks and gluons by reconstructing their hadronic decay products. An essential component of the detector is the calibration system, which was evaluated in terms of its misalignment, linearity, and resolution. In order to analyze the data, the authors created scripts in ROOT 5.02/00 and C++. The authors also used Mathematica 5.1 to perform complex mathematics and AutoCAD 2006 to produce optical ray traces. The misalignment of the optical components was found to be satisfactory; the Hybrid Photodiodes (HPDs) were confirmed to be linear; the constant, noise and stochastic contributions to its resolution were analyzed; and the quantum efficiency of most HPDs was determined to be approximately 40%. With a better understanding of the laser calibration system, one can further understand and improve the HCAL.

Army Combat Medic Resilience: The Process of Forging Loyalty.

PubMed

Abraham, Preetha A; Russell, Dale W; Huffman, Sarah; Deuster, Patricia; Gibbons, Susanne W

2018-03-01

This study presents a grounded theory analysis of in-depth interviews of United States Army Combat Medics (CMs) who had served in Iraq and/or Afghanistan. The study explores how 17 CMs nominated by their peers as resilient cope with military stressors in order to identify the factors that enable them to thrive amidst harsh conditions. Four distinct categories of characteristics unique to this group emerged: (1) social bonding, (2) readiness, (3) dual loyalty as performance, and (4) leader by example. Forging loyalty underpins these characteristics and represents the main process used by resilient CMs and comprised three behavior patterns: (1) commitment to the family, (2) commitment to the military mission, and (3) commitment to their guiding religious and spiritual beliefs. Prominent behavioral tendencies of forging loyalty likely developed during childhood and re-enforced by families, friends, and other role models. Based on the findings, new training and education efforts should focus on developing positive emotional, environmental, and social resources to enhance the health and well-being of service members and their families.

A Generalized Method of Image Analysis from an Intercorrelation Matrix which May Be Singular.

ERIC Educational Resources Information Center

Yanai, Haruo; Mukherjee, Bishwa Nath

1987-01-01

This generalized image analysis method is applicable to singular and non-singular correlation matrices (CMs). Using the orthogonal projector and a weaker generalized inverse matrix, image and anti-image covariance matrices can be derived from a singular CM. (SLD)

Fertility of CMS wheat is restored by two Rf loci located on a recombined acrocentric chromosome

PubMed Central

Castillo, Almudena; Atienza, Sergio G.; Martín, Azahara C.

2014-01-01

Cytoplasmic male sterility (CMS) results from incompatibility between nuclear and cytoplasmic genomes, and is characterized by the inability to produce viable pollen. The restoration of male fertility generally involves the introgression of nuclear genes, termed restorers of fertility (Rf). CMS has been widely used for hybrid seed production in many crops but not in wheat, partly owing to the complex genetics of fertility restoration. In this study, an acrocentric chromosome that restores pollen fertility of CMS wheat in Hordeum chilense cytoplasm (msH1 system) is studied. The results show that this chromosome, of H. chilense origin and named Hchac, originated from a complex reorganization of the short arm of chromosomes 1Hch (1HchS) and 6Hch (6HchS). Diversity arrays technology (DArT) markers and cytological analysis indicate that Hchac is a kind of `zebra-like′ chromosome composed of chromosome 1HchS and alternate fragments of interstitial and distal regions of chromosome 6HchS. PCR-based markers together with FISH, GISH, and meiotic pairing analysis support this result. A restorer of fertility gene, named Rf 6H ch S, has been identified on the short arm of chromosome 6HchS. Moreover, restoration by the addition of chromosome 1HchS has been observed at a very low frequency and under certain environmental conditions. Therefore, the results indicate the presence of two Rf genes on the acrocentric chromosome: Rf 6H ch S and Rf 1H ch S, the restoration potential of Rf 6H ch S being greater. The stable and high restoration of pollen fertility in the msH1 system is therefore the result of the interaction between these two restorer genes. PMID:25271260

Inpatient Consults and Complications During Primary Total Joint Arthroplasty in a Bundled Care Model.

PubMed

Baumgartner, Billy T; Karas, Vasili; Kildow, Beau J; Cunningham, Daniel J; Klement, Mitchell R; Green, Cindy L; Attarian, David E; Seyler, Thorsten M

2018-04-01

The Centers for Medicare and Medicaid Services (CMS) are implementing changes in hospital reimbursement models for total joint arthroplasty (TJA), moving to value-based bundled payments from the fee-for-service model. The purpose of this study is to identify consults and complications during the perioperative period that increase financial burden. We combined CMS payment data for inpatient, professional, and postoperative with retrospective review of patients undergoing primary TJA and developed profiles of patients included in the Comprehensive Care for Joint Replacement bundle undergoing TJA. Statistical comparison of episode inpatient events and payments was conducted. Multiple regression analysis was adjusted for length of stay, disposition, and Charlson-Deyo comorbidity profile. Median total payment was $21,577.36, which exceeded the median bundle target payment of $20,625.00. Adjusted analyses showed that psychiatry consults (increase of $73,123.32; P < .001), internal medicine consults ($5789.38; P ≤ .001), pulmonary embolism ($35,273.68; P < .001), intensive care unit admission ($14,078.37; P < .001), and deep vein thrombosis ($9471.26; P = .019) resulted in increased payments using multivariate analysis adjusted for length of stay, Charlson-Deyo comorbidities, and discharge disposition. Patients with inpatient complications such as pulmonary embolism and/or deep vein thrombosis, intensive care unit admission, and medical/psychiatric consultation exceeded the CMS target. Although study results showed typical complication rates, acute inpatient consultation significantly increased utilization beyond the CMS target even when adjusted for length of stay, patient comorbidities, and discharge. Needed medical care should continue to be a priority for inpatients, and allowance for individual outliers should be considered in policy discussions. Copyright © 2017 Elsevier Inc. All rights reserved.

Cross-Site Reliability of Human Induced Pluripotent Stem-Cell Derived Cardiomyocyte Based Safety Assays using Microelectrode Arrays: Results from a Blinded CiPA Pilot Study.

PubMed

Millard, Daniel; Dang, Qianyu; Shi, Hong; Zhang, Xiaou; Strock, Chris; Kraushaar, Udo; Zeng, Haoyu; Levesque, Paul; Lu, Hua-Rong; Guillon, Jean-Michel; Wu, Joseph C; Li, Yingxin; Luerman, Greg; Anson, Blake; Guo, Liang; Clements, Mike; Abassi, Yama A; Ross, James; Pierson, Jennifer; Gintant, Gary

2018-04-27

Recent in vitro cardiac safety studies demonstrate the ability of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to detect electrophysiologic effects of drugs. However, variability contributed by unique approaches, procedures, cell lines and reagents across laboratories makes comparisons of results difficult, leading to uncertainty about the role of hiPSC-CMs in defining proarrhythmic risk in drug discovery and regulatory submissions. A blinded pilot study was conducted to evaluate the electrophysiologic effects of eight well-characterized drugs on four cardiomyocyte lines using a standardized protocol across three microelectrode array (MEA) platforms (18 individual studies). Drugs were selected to define assay sensitivity of prominent repolarizing currents (E-4031 for IKr, JNJ303 for IKs) and depolarizing currents (nifedipine for ICaL, mexiletine for INa) as well as drugs affecting multi-channel block (flecainide, moxifloxacin, quinidine, and ranolazine). Inclusion criteria for final analysis was based on demonstrated sensitivity to IKr block (20% prolongation with E-4031) and L-type calcium current block (20% shortening with nifedipine). Despite differences in baseline characteristics across cardiomyocyte lines, multiple sites and instrument platforms, 10 of 18 studies demonstrated adequate sensitivity to IKr block with E-4031 and ICaL block with nifedipine for inclusion in the final analysis. Concentration-dependent effects on repolarization were observed with this qualified dataset consistent with known ionic mechanisms of single and multi-channel blocking drugs. hiPSC-CMs can detect repolarization effects elicited by single and multi-channel blocking drugs after defining pharmacologic sensitivity to IKr and ICaL block, supporting further validation efforts using hiPSC-CMs for cardiac safety studies.

Developmental changes in electrophysiological characteristics of human-induced pluripotent stem cell-derived cardiomyocytes.

PubMed

Ben-Ari, Meital; Naor, Shulamit; Zeevi-Levin, Naama; Schick, Revital; Ben Jehuda, Ronen; Reiter, Irina; Raveh, Amit; Grijnevitch, Inna; Barak, Omri; Rosen, Michael R; Weissman, Amir; Binah, Ofer

2016-12-01

Previous studies proposed that throughout differentiation of human induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs), only 3 types of action potentials (APs) exist: nodal-, atrial-, and ventricular-like. To investigate whether there are precisely 3 phenotypes or a continuum exists among them, we tested 2 hypotheses: (1) During culture development a cardiac precursor cell is present that-depending on age-can evolve into the 3 phenotypes. (2) The predominant pattern is early prevalence of a nodal phenotype, transient appearance of an atrial phenotype, evolution to a ventricular phenotype, and persistence of transitional phenotypes. To test these hypotheses, we (1) performed fluorescence-activated cell sorting analysis of nodal, atrial, and ventricular markers; (2) recorded APs from 280 7- to 95-day-old iPSC-CMs; and (3) analyzed AP characteristics. The major findings were as follows: (1) fluorescence-activated cell sorting analysis of 30- and 60-day-old cultures showed that an iPSC-CMs population shifts from the nodal to the atrial/ventricular phenotype while including significant transitional populations; (2) the AP population did not consist of 3 phenotypes; (3) culture aging was associated with a shift from nodal to ventricular dominance, with a transient (57-70 days) appearance of the atrial phenotype; and (4) beat rate variability was more prominent in nodal than in ventricular cardiomyocytes, while pacemaker current density increased in older cultures. From the onset of development in culture, the iPSC-CMs population includes nodal, atrial, and ventricular APs and a broad spectrum of transitional phenotypes. The most readily distinguishable phenotype is atrial, which appears only transiently yet dominates at 57-70 days of evolution. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

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.

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.

Analysis of tidal currents in the North Sea from shipboard acoustic Doppler current profiler data

NASA Astrophysics Data System (ADS)

Vindenes, Håvard; Orvik, Kjell Arild; Søiland, Henrik; Wehde, Henning

2018-06-01

North Sea tidal currents are determined by applying harmonic analysis to ship-borne acoustic Doppler current profiler data recorded from 1999 to 2016, covering large areas of the northern North Sea. Direct current measurement data sets of this magnitude are rare in the otherwise well investigated North Sea, and thus it is a valuable asset in studying and expanding our understanding of its tidal currents and circulation in general. The harmonic analysis is applied to a least squares fit of the current observations at a set of knot points. Results from the harmonic analysis compare favorably to tidal parameters estimated from observations from moored instruments. The analysis shows that the tides are characterized by strong semi-diurnal component, with amplitudes of the principal Lunar constituent ranging from 1.6 cm/s in the Skagerrak to 67 cm/s in the Fair Isle Channel. Diurnal tides are found to be approximately one fifth the strength of the predominant semi-diurnal constituent. Output from a regional barotropic tide model compares well to tidal current determined from the harmonic analysis of the Acoustic Doppler Current Profiler data.

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.

Comparative safety and effectiveness of perinatal antiretroviral therapies for HIV-infected women and their children: Systematic review and network meta-analysis including different study designs.

PubMed

Veroniki, Areti Angeliki; Antony, Jesmin; Straus, Sharon E; Ashoor, Huda M; Finkelstein, Yaron; Khan, Paul A; Ghassemi, Marco; Blondal, Erik; Ivory, John D; Hutton, Brian; Gough, Kevin; Hemmelgarn, Brenda R; Lillie, Erin; Vafaei, Afshin; Tricco, Andrea C

2018-01-01

Nearly all newly infected children acquire Human Immunodeficiency virus (HIV) via mother-to-child transmission (MTCT) during pregnancy, labour or breastfeeding from untreated HIV-positive mothers. Antiretroviral therapy (ART) is the standard care for pregnant women with HIV. However, evidence of ART effectiveness and harms in infants and children of HIV-positive pregnant women exposed to ART has been largely inconclusive. The aim of our systematic review and network meta-analysis (NMA) was to evaluate the comparative safety and effectiveness of ART drugs in children exposed to maternal HIV and ART (or no ART/placebo) across different study designs. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (inception until December 7, 2015). Primary outcomes were any congenital malformations (CMs; safety), including overall major and minor CMs, and mother-to-child transmission (MTCT; effectiveness). Random-effects Bayesian pairwise meta-analyses and NMAs were conducted. After screening 6,468 citations and 1,373 full-text articles, 90 studies of various study designs and 90,563 patients were included. The NMA on CMs (20 studies, 7,503 children, 16 drugs) found that none of the ART drugs examined here were associated with a significant increase in CMs. However, zidovudine administered with lamivudine and indinavir was associated with increased risk of preterm births, zidovudine administered with nevirapine was associated with increased risk of stillbirths, and lamivudine administered with stavudine and efavirenz was associated with increased risk of low birth weight. A NMA on MTCT (11 studies, 10,786 patients, 6 drugs) found that zidovudine administered once (odds ratio [OR] = 0.39, 95% credible interval [CrI]: 0.19-0.83) or twice (OR = 0.43, 95% CrI: 0.21-0.68) was associated with significantly reduced risk of MTCT. Our findings suggest that ART drugs are not associated with an increased risk of CMs, yet some may increase adverse birth events. Some ART drugs (e.g., zidovudine) effectively reduce MTCT.

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

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.

Longitudinal evaluation of corticospinal tract in patients with resected brainstem cavernous malformations using high-definition fiber tractography and diffusion connectometry analysis: preliminary experience.

PubMed

Faraji, Amir H; Abhinav, Kumar; Jarbo, Kevin; Yeh, Fang-Cheng; Shin, Samuel S; Pathak, Sudhir; Hirsch, Barry E; Schneider, Walter; Fernandez-Miranda, Juan C; Friedlander, Robert M

2015-11-01

Brainstem cavernous malformations (CMs) are challenging due to a higher symptomatic hemorrhage rate and potential morbidity associated with their resection. The authors aimed to preoperatively define the relationship of CMs to the perilesional corticospinal tracts (CSTs) by obtaining qualitative and quantitative data using high-definition fiber tractography. These data were examined postoperatively by using longitudinal scans and in relation to patients' symptomatology. The extent of involvement of the CST was further evaluated longitudinally using the automated "diffusion connectometry" analysis. Fiber tractography was performed with DSI Studio using a quantitative anisotropy (QA)-based generalized deterministic tracking algorithm. Qualitatively, CST was classified as being "disrupted" and/or "displaced." Quantitative analysis involved obtaining mean QA values for the CST and its perilesional and nonperilesional segments. The contralateral CST was used for comparison. Diffusion connectometry analysis included comparison of patients' data with a template from 90 normal subjects. Three patients (mean age 22 years) with symptomatic pontomesencephalic hemorrhagic CMs and varying degrees of hemiparesis were identified. The mean follow-up period was 37.3 months. Qualitatively, CST was partially disrupted and displaced in all. Direction of the displacement was different in each case and progressively improved corresponding with the patient's neurological status. No patient experienced neurological decline related to the resection. The perilesional mean QA percentage decreases supported tract disruption and decreased further over the follow-up period (Case 1, 26%-49%; Case 2, 35%-66%; and Case 3, 63%-78%). Diffusion connectometry demonstrated rostrocaudal involvement of the CST consistent with the quantitative data. Hemorrhagic brainstem CMs can disrupt and displace perilesional white matter tracts with the latter occurring in unpredictable directions. This requires the use of tractography to accurately define their orientation to optimize surgical entry point, minimize morbidity, and enhance neurological outcomes. Observed anisotropy decreases in the perilesional segments are consistent with neural injury following hemorrhagic insults. A model using these values in different CST segments can be used to longitudinally monitor its craniocaudal integrity. Diffusion connectometry is a complementary approach providing longitudinal information on the rostrocaudal involvement of the CST.

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.

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.

An intermittent rocking platform for integrated expansion and differentiation of human pluripotent stem cells to cardiomyocytes in suspended microcarrier cultures.

PubMed

Ting, Sherwin; Chen, Allen; Reuveny, Shaul; Oh, Steve

2014-09-01

The development of novel platforms for large scale production of human embryonic stem cells (hESC) derived cardiomyocytes (CM) becomes more crucial as the demand for CMs in preclinical trials, high throughput cardio toxicity assays and future regenerative therapeutics rises. To this end, we have designed a microcarrier (MC) suspension agitated platform that integrates pluripotent hESC expansion followed by CM differentiation in a continuous, homogenous process. Hydrodynamic shear stresses applied during the hESC expansion and CM differentiation steps drastically reduced the capability of the cells to differentiate into CMs. Applying vigorous stirring during pluripotent hESC expansion on Cytodex 1 MC in spinner cultures resulted in low CM yields in the following differentiation step (cardiac troponin-T (cTnT): 22.83±2.56%; myosin heavy chain (MHC): 19.30±5.31%). Whereas the lower shear experienced in side to side rocker (wave type) platform resulted in higher CM yields (cTNT: 47.50±7.35%; MHC: 42.85±2.64%). The efficiency of CM differentiation is also affected by the hydrodynamic shear stress applied during the first 3days of the differentiation stage. Even low shear applied continuously by side to side rocker agitation resulted in very low CM differentiation efficiency (cTnT<5%; MHC<2%). Simply by applying intermittent agitation during these 3days followed by continuous agitation for the subsequent 9days, CM differentiation efficiency can be substantially increased (cTNT: 65.73±10.73%; MHC: 59.73±9.17%). These yields are 38.3% and 39.3% higher (for cTnT and MHC respectively) than static culture control. During the hESC expansion phase, cells grew on continuously agitated rocker platform as pluripotent cell/MC aggregates (166±88×10(5)μm(2)) achieving a cell concentration of 3.74±0.55×10(6)cells/mL (18.89±2.82 fold expansion) in 7days. These aggregates were further differentiated into CMs using a WNT modulation differentiation protocol for the subsequent 12days on a rocking platform with an intermittent agitation regime during the first 3days. Collectively, the integrated MC rocker platform produced 190.5±58.8×10(6) CMs per run (31.75±9.74 CM/hESC seeded). The robustness of the system was demonstrated by using 2 cells lines, hESC (HES-3) and human induced pluripotent stem cell (hiPSC) IMR-90. The CM/MC aggregates formed extensive sarcomeres that exhibited cross-striations confirming cardiac ontogeny. Functionality of the CMs was demonstrated by monitoring the effect of inotropic drug, Isoproterenol on beating frequency. In conclusion, we have developed a simple robust and scalable platform that integrates both hESC expansion and CM differentiation in one unit process which is capable of meeting the need for large amounts of CMs. Copyright © 2014. Published by Elsevier B.V.

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

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

PubMed

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

2017-05-05

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

Antisense oligodeoxynucleotide inhibition of a swelling-activated cation channel in osteoblast-like osteosarcoma cells

NASA Technical Reports Server (NTRS)

Duncan, R. L.; Kizer, N.; Barry, E. L.; Friedman, P. A.; Hruska, K. A.

1996-01-01

By patch-clamp analysis, we have shown that chronic, intermittent mechanical strain (CMS) increases the activity of stretch-activated cation channels of osteoblast-like UMR-106.01 cells. CMS also produces a swelling-activated whole-cell conductance (Gm) regulated by varying strain levels. We questioned whether the swelling-activated conductance was produced by stretch-activated cation channel activity. We have identified a gene involved in the increase in conductance by using antisense oligodeoxynucleotides (ODN) derived from the alpha 1-subunit genes of calcium channels found in UMR-106.01 cells (alpha1S, alpha1C, and alpha1D). We demonstrate that alpha 1C antisense ODNs abolish the increase in Gm in response to hypotonic swelling following CMS. Antisense ODNs to alpha1S and alpha1D, sense ODNs to alpha1C, and sham permeabilization had no effect on the conductance increase. In addition, during cell-attached patch-clamp studies, antisense ODNs to alpha1c completely blocked the swelling-activated and stretch-activated nonselective cation channel response to strain. Antisense ODNs to alpha1S treatment produced no effect on either swelling-activated or stretch-activated cation channel activity. There were differences in the stretch-activated and swelling-activated cation channel activity, but whether they represent different channels could not be determined from our data. Our data indicate that the alpha1C gene product is involved in the Gm and the activation of the swelling-activated cation channels induced by CMS. The possibility that swelling-activated cation channel genes are members of the calcium channel superfamily exists, but if alpha1c is not the swelling-activated cation channel itself, then its expression is required for induction of swelling-activated cation channel activity by CMS.

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.

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.

Unplanned gait termination in individuals with multiple sclerosis.

PubMed

Roeing, Kathleen L; Moon, Yaejin; Sosnoff, Jacob J

2017-03-01

Despite the pervasive nature of gait impairment in multiple sclerosis (MS), there is limited information concerning the control of gait termination in individuals with MS. The purpose of this investigation was to examine unplanned gait termination with and without cognitive distractors in individuals with MS compared to healthy controls. Thirty-one individuals with MS and 14 healthy controls completed a series of unplanned gait termination tasks over a pressure sensitive walkway under distracting and non-distracting conditions. Individuals with MS were further broken down into groups based on assistive device use: (no assistive device (MS noAD ) n=18; and assistive device (MS AD ) n=13). Individuals with MS who walked with an assistive device (MS AD : 67.8±15.1cm/s) walked slower than individuals without an assistive device (MS noAD : 110.4±32.3cm/s, p<0.01) and controls (120.0±30.0cm/s; p<0.01). There was a significant reduction in velocity in the cognitively distracting condition (93.4±32.1cm/s) compared to the normal condition [108.8±36.2cm/s; F(1,43)=3.4, p=0.04]. All participants took longer to stop during the distracting condition (1.7±0.6s) than the non-distracting condition (1.4±0.4s; U=673.0 p<0.01). After controlling for gait velocity, post-hoc analysis revealed the MS AD group took significantly longer to stop compared to the control group (p=0.05). Further research investigating the control of unplanned gait termination in MS is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

Taiwan Earthquake Damage Index Sin Mei Nga* and Masataka Andob a* Department of Geology, Chinese Culture University, No. 55, Hwa-Kang Road, Yang-Ming-Shan, Taipei 11114, Taiwan b Institute of Earth Sciences, Academia Sinica, 128, Sec2, Academia Road, Nangang, Taipei 11529, Taiwan * Corresponding author. Tel.: +886 (02) 28 61 05 11 ext.26133 fax: +886 (02) 28 61 49 59 E-mail: wsw2@ulive.pccu.edu.tw or sin_mei_josephine_ng@hotmail.com

NASA Astrophysics Data System (ADS)

Ng, S.

2012-12-01

Taking advantage of a previous study and twelve-year, free-field strong motion data in Taiwan, a preliminary, five-level earthquake damage index is newly proposed: I-No (no damage), II-Very Light, III-Light, IV-Moderate, and V-Heavy. For index I, PGA and PGV are, respectively, <62.5 gal and <11 cm/s. Likewise, for index II, PGA is ≧62.5 and ≦187.5 gal; but, PGV is ≧11 and ≦35 cm/s. Similarly, PGA is ≧187.5 and ≦325 gal; but, PGV is ≧35 and ≦55 cm/s for index III. The corresponding PGA and PGV, for index IV, are ≧325 and ≦450 gal and ≧55 and ≦75 cm/s. Finally, for index V, PGA and PGV are respectively >450 gal and >75 cm/s. Ten damaging seismic events in the past twelve years are redefined using this new earthquake damage index, with the devastating Chi-Chi earthquake and one non-damaging event as reference earthquakes. This newly proposed index depicts seismic hazard of these earthquakes with higher accuracy when compared to the existing intensity scale in Taiwan region. For further analysis, Japan earthquakes are also plotted as references.

Uric Acid Level Has a J-Shaped Association with Arterial Stiffness in Korean Postmenopausal Women.

PubMed

Lee, Hyungbin; Jung, Young-Hyo; Kwon, Yu-Jin; Park, Byoungjin

2017-11-01

Uric acid has been reported to function both as an oxidant or antioxidant depending on the context. A previous study in the Korean population reported a positive linear association between serum uric acid level and arterial stiffness in men, but little is known about how serum uric acid level is related to the risk of increased arterial stiffness in Korean postmenopausal women. We performed a cross-sectional study of 293 subjects who participated in a health examination program run by the health promotion center of Gangnam Severance Hospital between October 2007 and July 2010. High brachial-ankle pulse wave velocity was defined as a brachial-ankle pulse wave velocity of more than 1,450 cm/s. The odds ratios (ORs) for high brachial-ankle pulse wave velocity were calculated using multivariate logistic regression analysis across uric acid quartiles after adjusting for other indicators of cardiovascular risk. The 293 postmenopausal women were divided into quartiles according to uric acid level. The mean brachial-ankle pulse wave velocity values of each quartile were as follows: Q1, 1,474 cm/s; Q2, 1,375 cm/s; Q3, 1,422 cm/s; Q4, 1,528 cm/s. The second quartile was designated as the control group based on mean brachial-ankle pulse wave velocity value. Multivariate adjusted ORs (95% confidence intervals) for brachial-ankle pulse wave velocity across the uric acid quartiles were 2.642 (Q1, 1.095-6.3373), 1.00, 4.305 (Q3, 1.798-10.307), and 4.375 (Q4, 1.923-9.949), after adjusting for confounding variables. Serum uric acid level has a J-shaped association with arterial stiffness in Korean postmenopausal women.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-01-01

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

Allelism analysis of BrRfp locus in different restorer lines and map-based cloning of a fertility restorer gene, BrRfp1, for pol CMS in Chinese cabbage (Brassica rapa L.).

PubMed

Zhang, Huamin; Wu, Junqing; Dai, Zihui; Qin, Meiling; Hao, Lingyu; Ren, Yanjing; Li, Qingfei; Zhang, Lugang

2017-03-01

In Chinese cabbage, there are two Rf loci for pol CMS and one of them was mapped to a 12.6-kb region containing a potential candidate gene encoding PPR protein. In Chinese cabbage (Brassica rapa), polima cytoplasmic male sterility (pol CMS) is an important CMS type and is widely used for hybrid breeding. By extensive test crossing in Chinese cabbage, four restorer lines (92s105, 01s325, 00s109, and 88s148) for pol CMS were screened. By analyzing the allelism of the four restorer lines, it was found that 92s105, 01s325, and 00s109 had the same "restorers of fertility" (Rf) locus (designated as BrRfp1), but 88s148 had a different Rf locus (designated as BrRfp2). For fine mapping the BrRfp1 locus of 92s105, a BC 1 F 1 population with 487 individuals and a BC 1 F 2 population with 2485 individuals were successively constructed. Using simple sequence repeat (SSR) markers developed from Brassica rapa reference genome and InDel markers derived from whole-genome resequencing data of 94c9 and 92s105, BrRfp1 was mapped to a 12.6-kb region containing a potential candidate gene encoding pentatricopeptide repeat-containing protein. Based on the nucleotide polymorphisms of the candidate gene sequence between the restoring and nonrestoring alleles, a co-segregating marker SC718 was developed, which would be helpful for hybrid breeding by marker-assisted screening and for detecting new restorer lines.

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

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.

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.

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

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.

A National Analysis of Medicaid Home and Community Based Services Waivers for People With Intellectual and Developmental Disabilities: FY 2015.

PubMed

Friedman, Carli

2017-10-01

Medicaid Home and Community Based Services (HCBS) 1915(c) waivers are the largest source of funding for the long term services and supports of people with intellectual and developmental disabilities (IDD). National-level analyses of HCBS IDD waivers are crucial because of the large variance across states, the recent CMS rule and regulation changes (CMS 2249-F/2296-F), and the ever changing economic and political landscape. Therefore, the aim of this study was to examine state waiver priorities for people with IDD. In FY 2015, 111 waivers projected spending $25.6 billion for approximately 630,000 people with IDD. The services with the most funding were residential habilitation, supports to live in one's own home, and day habilitation. However, our analysis revealed large discrepancies across states and services.

Estimating job runtime for CMS analysis jobs

NASA Astrophysics Data System (ADS)

Sfiligoi, I.

2014-06-01

The basic premise of pilot systems is to create an overlay scheduling system on top of leased resources. And by definition, leases have a limited lifetime, so any job that is scheduled on such resources must finish before the lease is over, or it will be killed and all the computation is wasted. In order to effectively schedule jobs to resources, the pilot system thus requires the expected runtime of the users' jobs. Past studies have shown that relying on user provided estimates is not a valid strategy, so the system should try to make an estimate by itself. This paper provides a study of the historical data obtained from the Compact Muon Solenoid (CMS) experiment's Analysis Operations submission system. Clear patterns are observed, suggesting that making prediction of an expected job lifetime range is achievable with high confidence level in this environment.

Penile vascular indices in surgically treated and conservatively treated penile fracture: does conventional immediate repair matter?

PubMed

Safarinejad, Mohammad Reza; Lashkari, Mohammad Hossein; Babaei, Alireza; Dadkhah, Farid; Kolahi, Ali Asghar

2012-12-01

To investigate the impact of immediate surgical repair and conservative treatment of penile fracture (PF) on penile vascular indices. The study includes 146 surgically treated (group 1), and 56 conservatively treated patients (group 2). All of the participants underwent penile duplex Doppler ultrasonography (PDDU), and Doppler parameters including the peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) were measured in both corpora at baseline and after intracavernosal injection of 20 μg prostaglandin E1. Univariable and multivariable Cox regression analysis addressed study variables. An increased number of men in group 2 (25.0%) compared with men in group 1 (19.2%) reported ED, but the difference did not reach statistical significance (P=0.06). In patients with ED the mean PSV did not differ significantly between the group 1 (30.1±4.02 cm/s) and group 2 (30.1±4.02 cm/s) (P=0.32). Also, in patients without ED, the mean PSV for group 1 (82.4±24.1 cm/s) subjects did not differ significantly from the means for the group 2 patients (79.4±27.2 cm/s) (P=0.21). Vascular hemodynamics in fractured corpus cavernosum did not differ significantly between two groups (P=0.08). Current method of surgical treatment does not provide better outcome in terms of erectile function and penile vascular hemodynamics.

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

40 CFR 63.7505 - What are my general requirements for complying with this subpart?

Code of Federal Regulations, 2011 CFR

2011-07-01

... compliance with the applicable emission limit for hydrogen chloride or mercury using fuel analysis if the..., fuel analysis, or continuous monitoring systems (CMS), including a continuous emission monitoring..., you must demonstrate compliance for hydrogen chloride or mercury using performance testing, if subject...

Toward a public analysis database for LHC new physics searches using M ADA NALYSIS 5

NASA Astrophysics Data System (ADS)

Dumont, B.; Fuks, B.; Kraml, S.; Bein, S.; Chalons, G.; Conte, E.; Kulkarni, S.; Sengupta, D.; Wymant, C.

2015-02-01

We present the implementation, in the MadAnalysis 5 framework, of several ATLAS and CMS searches for supersymmetry in data recorded during the first run of the LHC. We provide extensive details on the validation of our implementations and propose to create a public analysis database within this framework.

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. ...

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

NASA Astrophysics Data System (ADS)

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

2010-04-01

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

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.

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.

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.

Calcium-Alginate Hydrogel-Encapsulated Fibroblasts Provide Sustained Release of Vascular Endothelial Growth Factor

PubMed Central

Hunt, Nicola C.; Shelton, Richard M.; Henderson, Deborah J.

2013-01-01

Vascularization of engineered or damaged tissues is essential to maintain cell viability and proper tissue function. Revascularization of the left ventricle (LV) of the heart after myocardial infarction is particularly important, since hypoxia can give rise to chronic heart failure due to inappropriate remodeling of the LV after death of cardiomyocytes (CMs). Fibroblasts can express vascular endothelial growth factor (VEGF), which plays a major role in angiogenesis and also acts as a chemoattractant and survival factor for CMs and cardiac progenitors. In this in vitro model study, mouse NIH 3T3 fibroblasts encapsulated in 2% w/v Ca-alginate were shown to remain viable for 150 days. Semiquantitative reverse transcription–polymerase chain reaction and immunohistochemistry demonstrated that over 21 days of encapsulation, fibroblasts continued to express VEGF, while enzyme-linked immunosorbent assay showed that there was sustained release of VEGF from the Ca-alginate during this period. The scaffold degraded gradually over the 21 days, without reduction in volume. Cells released from the Ca-alginate at 7 and 21 days as a result of scaffold degradation were shown to retain viability, to adhere to fibronectin in a normal manner, and continue to express VEGF, demonstrating their potential to further contribute to maintenance of cardiac function after scaffold degradation. This model in vitro study therefore demonstrates that fibroblasts encapsulated in Ca-alginate provide sustained release of VEGF. PMID:23082964

Search for R-parity violating decays of a top squark in proton-proton collisions at √{ s} = 8 TeV

NASA Astrophysics Data System (ADS)

Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hartl, C.; Hörmann, N.; Hrubec, J.; Jeitler, M.; Knünz, V.; König, A.; Krammer, M.; Krätschmer, I.; Liko, D.; Matsushita, T.; Mikulec, I.; Rabady, D.; Rahbaran, B.; Rohringer, H.; Schieck, J.; Schöfbeck, R.; Strauss, J.; Treberer-Treberspurg, W.; Waltenberger, W.; Wulz, C.-E.; Mossolov, V.; Shumeiko, N.; Suarez Gonzalez, J.; Alderweireldt, S.; Cornelis, T.; de Wolf, E. A.; Janssen, X.; Knutsson, A.; Lauwers, J.; Luyckx, S.; van de Klundert, M.; van Haevermaet, H.; van Mechelen, P.; van Remortel, N.; van Spilbeeck, A.; Abu Zeid, S.; Blekman, F.; D'Hondt, J.; Daci, N.; de Bruyn, I.; Deroover, K.; Heracleous, N.; Keaveney, J.; Lowette, S.; Moreels, L.; Olbrechts, A.; Python, Q.; Strom, D.; Tavernier, S.; van Doninck, W.; van Mulders, P.; van Onsem, G. P.; van Parijs, I.; Barria, P.; Brun, H.; Caillol, C.; Clerbaux, B.; de Lentdecker, G.; Fasanella, G.; Favart, L.; Grebenyuk, A.; Karapostoli, G.; Lenzi, T.; Léonard, A.; Maerschalk, T.; Marinov, A.; Perniè, L.; Randle-Conde, A.; Seva, T.; Vander Velde, C.; Vanlaer, P.; Yonamine, R.; Zenoni, F.; Zhang, F.; Beernaert, K.; Benucci, L.; Cimmino, A.; Crucy, S.; Dobur, D.; Fagot, A.; Garcia, G.; Gul, M.; McCartin, J.; Ocampo Rios, A. A.; Poyraz, D.; Ryckbosch, D.; Salva, S.; Sigamani, M.; Tytgat, M.; van Driessche, W.; Yazgan, E.; Zaganidis, N.; Basegmez, S.; Beluffi, C.; Bondu, O.; Brochet, S.; Bruno, G.; Caudron, A.; Ceard, L.; da Silveira, G. G.; Delaere, C.; Favart, D.; Forthomme, L.; Giammanco, A.; Hollar, J.; Jafari, A.; Jez, P.; Komm, M.; Lemaitre, V.; Mertens, A.; Musich, M.; Nuttens, C.; Perrini, L.; Pin, A.; Piotrzkowski, K.; Popov, A.; Quertenmont, L.; Selvaggi, M.; Vidal Marono, M.; Beliy, N.; Hammad, G. H.; Aldá Júnior, W. L.; Alves, F. L.; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Hamer, M.; Hensel, C.; Moraes, A.; Pol, M. E.; Rebello Teles, P.; Belchior Batista Das Chagas, E.; Carvalho, W.; Chinellato, J.; Custódio, A.; da Costa, E. M.; de Jesus Damiao, D.; de Oliveira Martins, C.; Fonseca de Souza, S.; Huertas Guativa, L. M.; Malbouisson, H.; Matos Figueiredo, D.; Mora Herrera, C.; Mundim, L.; Nogima, H.; Prado da Silva, W. L.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Vilela Pereira, A.; Ahuja, S.; Bernardes, C. A.; de Souza Santos, A.; Dogra, S.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Moon, C. S.; Novaes, S. F.; Padula, Sandra S.; Romero Abad, D.; Ruiz Vargas, J. C.; Aleksandrov, A.; Hadjiiska, R.; Iaydjiev, P.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Vutova, M.; Dimitrov, A.; Glushkov, I.; Litov, L.; Pavlov, B.; Petkov, P.; Ahmad, M.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Cheng, T.; Du, R.; Jiang, C. H.; Plestina, R.; Romeo, F.; Shaheen, S. M.; Spiezia, A.; Tao, J.; Wang, C.; Wang, Z.; Zhang, H.; Asawatangtrakuldee, C.; Ban, Y.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Avila, C.; Cabrera, A.; Chaparro Sierra, L. F.; Florez, C.; Gomez, J. P.; Gomez Moreno, B.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Puljak, I.; Ribeiro Cipriano, P. M.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Kadija, K.; Luetic, J.; Micanovic, S.; Sudic, L.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Bodlak, M.; Finger, M.; Finger, M.; Assran, Y.; Elgammal, S.; Ellithi Kamel, A.; Mahmoud, M. 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M.; Bloch, P.; Bocci, A.; Bonato, A.; Botta, C.; Breuker, H.; Camporesi, T.; Castello, R.; Cerminara, G.; D'Alfonso, M.; D'Enterria, D.; Dabrowski, A.; Daponte, V.; David, A.; de Gruttola, M.; de Guio, F.; de Roeck, A.; de Visscher, S.; di Marco, E.; Dobson, M.; Dordevic, M.; Dorney, B.; Du Pree, T.; Duggan, D.; Dünser, M.; Dupont, N.; Elliott-Peisert, A.; Franzoni, G.; Fulcher, J.; Funk, W.; Gigi, D.; Gill, K.; Giordano, D.; Girone, M.; Glege, F.; Guida, R.; Gundacker, S.; Guthoff, M.; Hammer, J.; Harris, P.; Hegeman, J.; Innocente, V.; Janot, P.; Kirschenmann, H.; Kortelainen, M. J.; Kousouris, K.; Krajczar, K.; Lecoq, P.; Lourenço, C.; Lucchini, M. T.; Magini, N.; Malgeri, L.; Mannelli, M.; Martelli, A.; Masetti, L.; Meijers, F.; Mersi, S.; Meschi, E.; Moortgat, F.; Morovic, S.; Mulders, M.; Nemallapudi, M. V.; Neugebauer, H.; Orfanelli, S.; Orsini, L.; Pape, L.; Perez, E.; Peruzzi, M.; Petrilli, A.; Petrucciani, G.; Pfeiffer, A.; Pierini, M.; Piparo, D.; Racz, A.; Reis, T.; Rolandi, G.; Rovere, M.; Ruan, M.; Sakulin, H.; Schäfer, C.; Schwick, C.; Seidel, M.; Sharma, A.; Silva, P.; Simon, M.; Sphicas, P.; Steggemann, J.; Stieger, B.; Stoye, M.; Takahashi, Y.; Treille, D.; Triossi, A.; Tsirou, A.; Veres, G. I.; Wardle, N.; Wöhri, H. K.; Zagozdzinska, A.; Zeuner, W. D.; Bertl, W.; Deiters, K.; Erdmann, W.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; Langenegger, U.; Renker, D.; Rohe, T.; Bachmair, F.; Bäni, L.; Bianchini, L.; Casal, B.; Dissertori, G.; Dittmar, M.; Donegà, M.; Eller, P.; Grab, C.; Heidegger, C.; Hits, D.; Hoss, J.; Kasieczka, G.; Lustermann, W.; Mangano, B.; Marionneau, M.; Martinez Ruiz Del Arbol, P.; Masciovecchio, M.; Meister, D.; Micheli, F.; Musella, P.; Nessi-Tedaldi, F.; Pandolfi, F.; Pata, J.; Pauss, F.; Perrozzi, L.; Quittnat, M.; Rossini, M.; Schönenberger, M.; Starodumov, A.; Takahashi, M.; Tavolaro, V. R.; Theofilatos, K.; Wallny, R.; Aarrestad, T. K.; Amsler, C.; Caminada, L.; Canelli, M. F.; Chiochia, V.; de Cosa, A.; Galloni, C.; Hinzmann, A.; Hreus, T.; Kilminster, B.; Lange, C.; Ngadiuba, J.; Pinna, D.; Rauco, G.; Robmann, P.; Ronga, F. J.; Salerno, D.; Yang, Y.; Cardaci, M.; Chen, K. H.; Doan, T. H.; Jain, Sh.; Khurana, R.; Konyushikhin, M.; Kuo, C. M.; Lin, W.; Lu, Y. J.; Pozdnyakov, A.; Yu, S. S.; Kumar, Arun; Bartek, R.; Chang, P.; Chang, Y. H.; Chang, Y. W.; Chao, Y.; Chen, K. F.; Chen, P. H.; Dietz, C.; Fiori, F.; Grundler, U.; Hou, W.-S.; Hsiung, Y.; Liu, Y. F.; Lu, R.-S.; Miñano Moya, M.; Petrakou, E.; Tsai, J. F.; Tzeng, Y. M.; Asavapibhop, B.; Kovitanggoon, K.; Singh, G.; Srimanobhas, N.; Suwonjandee, N.; Adiguzel, A.; Bakirci, M. N.; Demiroglu, Z. S.; Dozen, C.; Eskut, E.; Gecit, F. H.; Girgis, S.; Gokbulut, G.; Guler, Y.; Gurpinar, E.; Hos, I.; Kangal, E. E.; Onengut, G.; Ozcan, M.; Ozdemir, K.; Ozturk, S.; Sunar Cerci, D.; Tali, B.; Topakli, H.; Vergili, M.; Zorbilmez, C.; Akin, I. V.; Bilin, B.; Bilmis, S.; Isildak, B.; Karapinar, G.; Yalvac, M.; Zeyrek, M.; Gülmez, E.; Kaya, M.; Kaya, O.; Yetkin, E. A.; Yetkin, T.; Cakir, A.; Cankocak, K.; Sen, S.; Vardarlı, F. I.; Grynyov, B.; Levchuk, L.; Sorokin, P.; Aggleton, R.; Ball, F.; Beck, L.; Brooke, J. J.; Clement, E.; Cussans, D.; Flacher, H.; Goldstein, J.; Grimes, M.; Heath, G. P.; Heath, H. F.; Jacob, J.; Kreczko, L.; Lucas, C.; Meng, Z.; Newbold, D. M.; Paramesvaran, S.; Poll, A.; Sakuma, T.; Seif El Nasr-Storey, S.; Senkin, S.; Smith, D.; Smith, V. J.; Bell, K. W.; Belyaev, A.; Brew, C.; Brown, R. M.; Calligaris, L.; Cieri, D.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Olaiya, E.; Petyt, D.; Shepherd-Themistocleous, C. H.; Thea, A.; Tomalin, I. R.; Williams, T.; Worm, S. D.; Baber, M.; Bainbridge, R.; Buchmuller, O.; Bundock, A.; Burton, D.; Casasso, S.; Citron, M.; Colling, D.; Corpe, L.; Dauncey, P.; Davies, G.; de Wit, A.; Della Negra, M.; Dunne, P.; Elwood, A.; Futyan, D.; Hall, G.; Iles, G.; Lane, R.; Lucas, R.; Lyons, L.; Magnan, A.-M.; Malik, S.; Nash, J.; Nikitenko, A.; Pela, J.; Pesaresi, M.; Petridis, K.; Raymond, D. M.; Richards, A.; Rose, A.; Seez, C.; Tapper, A.; Uchida, K.; Vazquez Acosta, M.; Virdee, T.; Zenz, S. C.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Leggat, D.; Leslie, D.; Reid, I. D.; Symonds, P.; Teodorescu, L.; Turner, M.; Borzou, A.; Call, K.; Dittmann, J.; Hatakeyama, K.; Liu, H.; Pastika, N.; Charaf, O.; Cooper, S. I.; Henderson, C.; Rumerio, P.; Arcaro, D.; Avetisyan, A.; Bose, T.; Fantasia, C.; Gastler, D.; Lawson, P.; Rankin, D.; Richardson, C.; Rohlf, J.; St. John, J.; Sulak, L.; Zou, D.; Alimena, J.; Berry, E.; Bhattacharya, S.; Cutts, D.; Ferapontov, A.; Garabedian, A.; Hakala, J.; Heintz, U.; Laird, E.; Landsberg, G.; Mao, Z.; Narain, M.; Piperov, S.; Sagir, S.; Syarif, R.; Breedon, R.; Breto, G.; Calderon de La Barca Sanchez, M.; Chauhan, S.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Erbacher, R.; Funk, G.; Gardner, M.; Ko, W.; Lander, R.; McLean, C.; Mulhearn, M.; Pellett, D.; Pilot, J.; Ricci-Tam, F.; Shalhout, S.; Smith, J.; Squires, M.; Stolp, D.; Tripathi, M.; Wilbur, S.; Yohay, R.; Cousins, R.; Everaerts, P.; Florent, A.; Hauser, J.; Ignatenko, M.; Saltzberg, D.; Takasugi, E.; Valuev, V.; Weber, M.; Burt, K.; Clare, R.; Ellison, J.; Gary, J. W.; Hanson, G.; Heilman, J.; Ivova Paneva, M.; Jandir, P.; Kennedy, E.; Lacroix, F.; Long, O. R.; Luthra, A.; Malberti, M.; Olmedo Negrete, M.; Shrinivas, A.; Wei, H.; Wimpenny, S.; Yates, B. R.; Branson, J. G.; Cerati, G. B.; Cittolin, S.; D'Agnolo, R. T.; Derdzinski, M.; Holzner, A.; Kelley, R.; Klein, D.; Letts, J.; MacNeill, I.; Olivito, D.; Padhi, S.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Tadel, M.; Vartak, A.; Wasserbaech, S.; Welke, C.; Würthwein, F.; Yagil, A.; Zevi Della Porta, G.; Bradmiller-Feld, J.; Campagnari, C.; Dishaw, A.; Dutta, V.; Flowers, K.; Franco Sevilla, M.; Geffert, P.; George, C.; Golf, F.; Gouskos, L.; Gran, J.; Incandela, J.; McColl, N.; Mullin, S. D.; Richman, J.; Stuart, D.; Suarez, I.; West, C.; Yoo, J.; Anderson, D.; Apresyan, A.; Bornheim, A.; Bunn, J.; Chen, Y.; Duarte, J.; Mott, A.; Newman, H. B.; Pena, C.; Spiropulu, M.; Vlimant, J. R.; Xie, S.; Zhu, R. Y.; Andrews, M. B.; Azzolini, V.; Calamba, A.; Carlson, B.; Ferguson, T.; Paulini, M.; Russ, J.; Sun, M.; Vogel, H.; Vorobiev, I.; Cumalat, J. P.; Ford, W. T.; Gaz, A.; Jensen, F.; Johnson, A.; Krohn, M.; Mulholland, T.; Nauenberg, U.; Stenson, K.; Wagner, S. R.; Alexander, J.; Chatterjee, A.; Chaves, J.; Chu, J.; Dittmer, S.; Eggert, N.; Mirman, N.; Nicolas Kaufman, G.; Patterson, J. R.; Rinkevicius, A.; Ryd, A.; Skinnari, L.; Soffi, L.; Sun, W.; Tan, S. M.; Teo, W. D.; Thom, J.; Thompson, J.; Tucker, J.; Weng, Y.; Wittich, P.; Abdullin, S.; Albrow, M.; Apollinari, G.; Banerjee, S.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bolla, G.; Burkett, K.; Butler, J. N.; Cheung, H. W. K.; Chlebana, F.; Cihangir, S.; Elvira, V. D.; Fisk, I.; Freeman, J.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Hanlon, J.; Hare, D.; Harris, R. M.; Hasegawa, S.; Hirschauer, J.; Hu, Z.; Jayatilaka, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kreis, B.; Lammel, S.; Linacre, J.; Lincoln, D.; Lipton, R.; Liu, T.; Lopes de Sá, R.; Lykken, J.; Maeshima, K.; Marraffino, J. M.; Maruyama, S.; Mason, D.; McBride, P.; Merkel, P.; Mrenna, S.; Nahn, S.; Newman-Holmes, C.; O'Dell, V.; Pedro, K.; Prokofyev, O.; Rakness, G.; Sexton-Kennedy, E.; Soha, A.; Spalding, W. J.; Spiegel, L.; Strobbe, N.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vernieri, C.; Verzocchi, M.; Vidal, R.; Weber, H. A.; Whitbeck, A.; Acosta, D.; Avery, P.; Bortignon, P.; Bourilkov, D.; Carnes, A.; Carver, M.; Curry, D.; Das, S.; Field, R. D.; Furic, I. K.; Gleyzer, S. V.; Konigsberg, J.; Korytov, A.; Kotov, K.; Ma, P.; Matchev, K.; Mei, H.; Milenovic, P.; Mitselmakher, G.; Rank, D.; Rossin, R.; Shchutska, L.; Snowball, M.; Sperka, D.; Terentyev, N.; Thomas, L.; Wang, J.; Wang, S.; Yelton, J.; Hewamanage, S.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Ackert, A.; Adams, J. R.; Adams, T.; Askew, A.; Bein, S.; Bochenek, J.; Diamond, B.; Haas, J.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Khatiwada, A.; Prosper, H.; Weinberg, M.; Baarmand, M. M.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Kalakhety, H.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Bucinskaite, I.; Cavanaugh, R.; Evdokimov, O.; Gauthier, L.; Gerber, C. E.; Hofman, D. J.; Kurt, P.; O'Brien, C.; Sandoval Gonzalez, I. D.; Turner, P.; Varelas, N.; Wu, Z.; Zakaria, M.; Bilki, B.; Clarida, W.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Snyder, C.; Tiras, E.; Wetzel, J.; Yi, K.; Anderson, I.; Barnett, B. A.; Blumenfeld, B.; Eminizer, N.; Fehling, D.; Feng, L.; Gritsan, A. V.; Maksimovic, P.; Martin, C.; Osherson, M.; Roskes, J.; Sady, A.; Sarica, U.; Swartz, M.; Xiao, M.; Xin, Y.; You, C.; Baringer, P.; Bean, A.; Benelli, G.; Bruner, C.; Kenny, R. P.; Majumder, D.; Malek, M.; Murray, M.; Sanders, S.; Stringer, R.; Wang, Q.; Ivanov, A.; Kaadze, K.; Khalil, S.; Makouski, M.; Maravin, Y.; Mohammadi, A.; Saini, L. K.; Skhirtladze, N.; Toda, S.; Lange, D.; Rebassoo, F.; Wright, D.; Anelli, C.; Baden, A.; Baron, O.; Belloni, A.; Calvert, B.; Eno, S. C.; Ferraioli, C.; Gomez, J. A.; Hadley, N. J.; Jabeen, S.; Kellogg, R. G.; Kolberg, T.; Kunkle, J.; Lu, Y.; Mignerey, A. C.; Shin, Y. H.; Skuja, A.; Tonjes, M. B.; Tonwar, S. C.; Apyan, A.; Barbieri, R.; Baty, A.; Bierwagen, K.; Brandt, S.; Busza, W.; Cali, I. A.; Demiragli, Z.; Di Matteo, L.; Gomez Ceballos, G.; Goncharov, M.; Gulhan, D.; Iiyama, Y.; Innocenti, G. M.; Klute, M.; Kovalskyi, D.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Marini, A. C.; McGinn, C.; Mironov, C.; Narayanan, S.; Niu, X.; Paus, C.; Roland, C.; Roland, G.; Salfeld-Nebgen, J.; Stephans, G. S. F.; Sumorok, K.; Varma, M.; Velicanu, D.; Veverka, J.; Wang, J.; Wang, T. W.; Wyslouch, B.; Yang, M.; Zhukova, V.; Dahmes, B.; Evans, A.; Finkel, A.; Gude, A.; Hansen, P.; Kalafut, S.; Kao, S. C.; Klapoetke, K.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Tambe, N.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bloom, K.; Bose, S.; Claes, D. R.; Dominguez, A.; Fangmeier, C.; Gonzalez Suarez, R.; Kamalieddin, R.; Knowlton, D.; Kravchenko, I.; Meier, F.; Monroy, J.; Ratnikov, F.; Siado, J. E.; Snow, G. R.; Alyari, M.; Dolen, J.; George, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Kaisen, J.; Kharchilava, A.; Kumar, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Baumgartel, D.; Chasco, M.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Teixeira de Lima, R.; Trocino, D.; Wang, R.-J.; Wood, D.; Zhang, J.; Hahn, K. A.; Kubik, A.; Low, J. F.; Mucia, N.; Odell, N.; Pollack, B.; Schmitt, M.; Stoynev, S.; Sung, K.; Trovato, M.; Velasco, M.; Brinkerhoff, A.; Dev, N.; Hildreth, M.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Smith, G.; Taroni, S.; Valls, N.; Wayne, M.; Wolf, M.; Woodard, A.; Antonelli, L.; Brinson, J.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Hart, A.; Hill, C.; Hughes, R.; Ji, W.; Ling, T. Y.; Liu, B.; Luo, W.; Puigh, D.; Rodenburg, M.; Winer, B. L.; Wulsin, H. W.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Koay, S. A.; Lujan, P.; Marlow, D.; Medvedeva, T.; Mooney, M.; Olsen, J.; Palmer, C.; Piroué, P.; Saka, H.; Stickland, D.; Tully, C.; Zuranski, A.; Malik, S.; Barker, A.; Barnes, V. E.; Benedetti, D.; Bortoletto, D.; Gutay, L.; Jha, M. K.; Jones, M.; Jung, A. W.; Jung, K.; Miller, D. H.; Neumeister, N.; Radburn-Smith, B. C.; Shi, X.; Shipsey, I.; Silvers, D.; Sun, J.; Svyatkovskiy, A.; Wang, F.; Xie, W.; Xu, L.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Chen, Z.; Ecklund, K. M.; Geurts, F. J. M.; Guilbaud, M.; Li, W.; Michlin, B.; Northup, M.; Padley, B. P.; Redjimi, R.; Roberts, J.; Rorie, J.; Tu, Z.; Zabel, J.; Betchart, B.; Bodek, A.; de Barbaro, P.; Demina, R.; Eshaq, Y.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Han, J.; Harel, A.; Hindrichs, O.; Khukhunaishvili, A.; Petrillo, G.; Tan, P.; Verzetti, M.; Arora, S.; Chou, J. P.; Contreras-Campana, C.; Contreras-Campana, E.; Ferencek, D.; Gershtein, Y.; Gray, R.; Halkiadakis, E.; Hidas, D.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Lath, A.; Nash, K.; Panwalkar, S.; Park, M.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Foerster, M.; Riley, G.; Rose, K.; Spanier, S.; Bouhali, O.; Castaneda Hernandez, A.; Celik, A.; Dalchenko, M.; de Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Kamon, T.; Krutelyov, V.; Mueller, R.; Osipenkov, I.; Pakhotin, Y.; Patel, R.; Perloff, A.; Rose, A.; Safonov, A.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Cowden, C.; Damgov, J.; Dragoiu, C.; Dudero, P. R.; Faulkner, J.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Undleeb, S.; Volobouev, I.; Appelt, E.; Delannoy, A. G.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Mao, Y.; Melo, A.; Ni, H.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Cox, B.; Francis, B.; Goodell, J.; Hirosky, R.; Ledovskoy, A.; Li, H.; Lin, C.; Neu, C.; Sinthuprasith, T.; Sun, X.; Wang, Y.; Wolfe, E.; Wood, J.; Xia, F.; Clarke, C.; Harr, R.; Karchin, P. E.; Kottachchi Kankanamge Don, C.; Lamichhane, P.; Sturdy, J.; Belknap, D. A.; Carlsmith, D.; Cepeda, M.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Hall-Wilton, R.; Herndon, M.; Hervé, A.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Mohapatra, A.; Ojalvo, I.; Perry, T.; Pierro, G. A.; Polese, G.; Ruggles, T.; Sarangi, T.; Savin, A.; Sharma, A.; Smith, N.; Smith, W. H.; Taylor, D.; Woods, N.; Cms Collaboration

2016-09-01

The results of a search for a supersymmetric partner of the top quark (top squark), pair-produced in proton-proton collisions at √{ s} = 8 TeV, are presented. The search, which focuses on R-parity violating, chargino-mediated decays of the top squark, is performed in final states with low missing transverse momentum, two oppositely charged electrons or muons, and at least five jets. The analysis uses a data sample corresponding to an integrated luminosity of 19.7 fb-1 collected with the CMS detector at the LHC in 2012. The data are found to be in agreement with the standard model expectation, and upper limits are placed on the top squark pair production cross section at 95% confidence level. Assuming a 100% branching fraction for the top squark decay chain, t ˜ → t χ˜1±, χ˜1± →ℓ± + jj , top squark masses less than 890 (1000) GeV for the electron (muon) channel are excluded for the first time in models with a single nonzero R-parity violating coupling λijk‧ (i , j , k ≤ 2), where i , j , k correspond to the three generations.

Evaluation of Changes in Morphology and Function of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (HiPSC-CMs) Cultured on an Aligned-Nanofiber Cardiac Patch

PubMed Central

Khan, Mahmood; Xu, Yanyi; Hua, Serena; Johnson, Jed; Belevych, Andriy; Janssen, Paul M. L.; Gyorke, Sandor; Guan, Jianjun; Angelos, Mark G.

2015-01-01

Introduction Dilated cardiomyopathy is a major cause of progressive heart failure. Utilization of stem cell therapy offers a potential means of regenerating viable cardiac tissue. However, a major obstacle to stem cell therapy is the delivery and survival of implanted stem cells in the ischemic heart. To address this issue, we have developed a biomimetic aligned nanofibrous cardiac patch and characterized the alignment and function of human inducible pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) cultured on this cardiac patch. This hiPSC-CMs seeded patch was compared with hiPSC-CMs cultured on standard flat cell culture plates. Methods hiPSC-CMs were cultured on; 1) a highly aligned polylactide-co-glycolide (PLGA) nanofiber scaffold (~50 microns thick) and 2) on a standard flat culture plate. Scanning electron microscopy (SEM) was used to determine alignment of PLGA nanofibers and orientation of the cells on the respective surfaces. Analysis of gap junctions (Connexin-43) was performed by confocal imaging in both the groups. Calcium cycling and patch-clamp technique were performed to measure calcium transients and electrical coupling properties of cardiomyocytes. Results SEM demonstrated >90% alignment of the nanofibers in the patch which is similar to the extracellular matrix of decellularized rat myocardium. Confocal imaging of the cardiomyocytes demonstrated symmetrical alignment in the same direction on the aligned nanofiber patch in sharp contrast to the random appearance of cardiomyocytes cultured on a tissue culture plate. The hiPSC-CMs cultured on aligned nanofiber cardiac patches showed more efficient calcium cycling compared with cells cultured on standard flat surface culture plates. Quantification of mRNA with qRT-PCR confirmed that these cardiomyocytes expressed α-actinin, troponin-T and connexin-43 in-vitro. Conclusions Overall, our results demonstrated changes in morphology and function of human induced pluripotent derived cardiomyocytes cultured in an anisotropic environment created by an aligned nanofiber patch. In this environment, these cells better approximate normal cardiac tissue compared with cells cultured on flat surface and can serve as the basis for bioengineering of an implantable cardiac patch. PMID:25993466

Evaluation of Changes in Morphology and Function of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (HiPSC-CMs) Cultured on an Aligned-Nanofiber Cardiac Patch.

PubMed

Khan, Mahmood; Xu, Yanyi; Hua, Serena; Johnson, Jed; Belevych, Andriy; Janssen, Paul M L; Gyorke, Sandor; Guan, Jianjun; Angelos, Mark G

2015-01-01

Dilated cardiomyopathy is a major cause of progressive heart failure. Utilization of stem cell therapy offers a potential means of regenerating viable cardiac tissue. However, a major obstacle to stem cell therapy is the delivery and survival of implanted stem cells in the ischemic heart. To address this issue, we have developed a biomimetic aligned nanofibrous cardiac patch and characterized the alignment and function of human inducible pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) cultured on this cardiac patch. This hiPSC-CMs seeded patch was compared with hiPSC-CMs cultured on standard flat cell culture plates. hiPSC-CMs were cultured on; 1) a highly aligned polylactide-co-glycolide (PLGA) nanofiber scaffold (~50 microns thick) and 2) on a standard flat culture plate. Scanning electron microscopy (SEM) was used to determine alignment of PLGA nanofibers and orientation of the cells on the respective surfaces. Analysis of gap junctions (Connexin-43) was performed by confocal imaging in both the groups. Calcium cycling and patch-clamp technique were performed to measure calcium transients and electrical coupling properties of cardiomyocytes. SEM demonstrated >90% alignment of the nanofibers in the patch which is similar to the extracellular matrix of decellularized rat myocardium. Confocal imaging of the cardiomyocytes demonstrated symmetrical alignment in the same direction on the aligned nanofiber patch in sharp contrast to the random appearance of cardiomyocytes cultured on a tissue culture plate. The hiPSC-CMs cultured on aligned nanofiber cardiac patches showed more efficient calcium cycling compared with cells cultured on standard flat surface culture plates. Quantification of mRNA with qRT-PCR confirmed that these cardiomyocytes expressed α-actinin, troponin-T and connexin-43 in-vitro. Overall, our results demonstrated changes in morphology and function of human induced pluripotent derived cardiomyocytes cultured in an anisotropic environment created by an aligned nanofiber patch. In this environment, these cells better approximate normal cardiac tissue compared with cells cultured on flat surface and can serve as the basis for bioengineering of an implantable cardiac patch.

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

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...

From the CMS Computing Experience in the WLCG STEP'09 Challenge to the First Data Taking of the LHC Era

NASA Astrophysics Data System (ADS)

Bonacorsi, D.; Gutsche, O.

The Worldwide LHC Computing Grid (WLCG) project decided in March 2009 to perform scale tests of parts of its overall Grid infrastructure before the start of the LHC data taking. The "Scale Test for the Experiment Program" (STEP'09) was performed mainly in June 2009 -with more selected tests in September- October 2009 -and emphasized the simultaneous test of the computing systems of all 4 LHC experiments. CMS tested its Tier-0 tape writing and processing capabilities. The Tier-1 tape systems were stress tested using the complete range of Tier-1 work-flows: transfer from Tier-0 and custody of data on tape, processing and subsequent archival, redistribution of datasets amongst all Tier-1 sites as well as burst transfers of datasets to Tier-2 sites. The Tier-2 analysis capacity was tested using bulk analysis job submissions to backfill normal user activity. In this talk, we will report on the different performed tests and present their post-mortem analysis.

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.

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.

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.